Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
- /
- 1513-7368(pISSN)
- /
- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
KSCI- Volume 17 Issue 12
- Volume 17 Issue 11
- Volume 17 Issue 10
- Volume 17 Issue 9
- Volume 17 Issue 8
- Volume 17 Issue 7
- Volume 17 Issue sup3
- Volume 17 Issue 6
- Volume 17 Issue 5
- Volume 17 Issue sup2
- Volume 17 Issue sup1
- Volume 17 Issue 4
- Volume 17 Issue 3
- Volume 17 Issue 2
- Volume 17 Issue 1
- Volume 16 Issue 18
- Volume 16 Issue 17
- Volume 16 Issue 16
- Volume 16 Issue 15
- Volume 16 Issue 14
- Volume 16 Issue 13
- Volume 16 Issue 12
- Volume 16 Issue 11
- Volume 16 Issue 10
- Volume 16 Issue 9
- Volume 16 Issue 8
- Volume 16 Issue 7
- Volume 16 Issue 6
- Volume 16 Issue 5
- Volume 16 Issue 4
- Volume 16 Issue 3
- Volume 16 Issue 2
- Volume 16 Issue 1
- Volume 15 Issue 24
- Volume 15 Issue 23
- Volume 15 Issue 22
- Volume 15 Issue 21
- Volume 15 Issue 20
- Volume 15 Issue 19
- Volume 15 Issue 18
- Volume 15 Issue 17
- Volume 15 Issue 16
- Volume 15 Issue 15
- Volume 15 Issue 14
- Volume 15 Issue 13
- Volume 15 Issue 12
- Volume 15 Issue 11
- Volume 15 Issue 10
- Volume 15 Issue 9
- Volume 15 Issue 8
- Volume 15 Issue 7
- Volume 15 Issue 6
- Volume 15 Issue 5
- Volume 15 Issue 4
- Volume 15 Issue 3
- Volume 15 Issue 2
- Volume 15 Issue 1
Volume 15 Issue 1
-
Moore, Malcolm Anthony;Lim, Min-Kyung;Huang, Xinen 1
-
Akaza, Hideyuki;Kawahara, Norie;Roh, Jae Kyung;Inoue, Hajime;Park, Eun-Cheol;Lee, Kwang-Sig;Kim, Sukyeong;Hayre, Jasdeep;Naidoo, Bhash;Wilkinson, Thomas;Fukuda, Takashi;Jang, Woo Ick;Nogimori, Masafumi 3
The Japan National Committee for the Union for International Cancer Control (UICC) and UICC-Asia Regional Office (ARO) organized an international session as part of the official program of the 72nd Annual Meeting of the Japanese Cancer Association to discuss the topic "What is cost-effectiveness in cancer treatment?" Healthcare economics are an international concern and a key issue for the UICC. The presenters and participants discussed the question of how limited medical resources can be best used to support life, which is a question that applies to both developing and industrialized countries, given that cancer treatment is putting medical systems under increasing strain. The emergence of advanced yet hugely expensive drugs has prompted discussion on methodologies for Health Technology Assessment (HTA) that seek to quantify cost and effect. The session benefited from the participation of various stakeholders, including representatives of industry, government and academia and three speakers from the Republic of Korea, an Asian country where discussion on HTA methodologies is already advanced. In addition, the session was joined by a representative of National Institute for Health and Care Excellence (NICE) of the United Kingdom, which has pioneered the concept of cost-effectiveness in a medical context. The aim of the session was to advance and deepen understanding of the issue of cost-effectiveness as viewed from medical care systems in different regions. -
Hu, Qing;Luo, Zhou;Xu, Tao;Zhang, Jun-Ying;Zhu, Ying;Chen, Wei-Xian;Zhong, Shan-Liang;Zhao, Jian-Hua;Tang, Jin-Hai 11
Accurate diagnosis and proper monitoring of cancer patients remain important obstacles for successful cancer treatment. The search for cancer biomarkers can aid in more accurate prediction of clinical outcome and may also reveal novel predictive factors and therapeutic targets. One such prognostic marker seems to be FOXA1. Many studies have shown that FOXA1 is strongly expressed in a vast majority of cancers, including breast cancer, in which high expression is associated with a good prognosis. In this review, we summarize the role of this transcription factor in the development and prognosis of breast cancer in the hope of providing insights into utility of FOXA1 as a novel biomarker. -
Gastric cancer is highly invasive, aggressively malignant, and amongst the most prevalent of all forms of cancer. Despite improved management strategies, early stage diagnosis of gastric cancer and accurate prognostic assessment is still lacking. Several recent reports have indicated that the pathogenesis of gastric cancer involves complex molecular mechanisms and multiple genetic and epigenetic alterations in oncogenes and tumor suppressor genes. Functional inactivation of the tumor suppressor protein PTEN (Phosphatase and Tensin Homolog) has been detected in multiple cases of gastric cancer, and already shown to be closely linked to the development, progression and prognosis of the disease. Inactivation of PTEN can be attributed to gene mutation, loss of heterozygosity, promoter hypermethylation, microRNA- mediated regulation of gene expression, and post-translational phosphorylation. PTEN is also involved in mechanisms regulating tumor resistance to chemotherapy. This review provides a comprehensive analysis of PTEN and its roles in gastric cancer, and emphasizes its potential benefits in early diagnosis and gene therapy-based treatment strategies.
-
Cheung, Min Rex;Kang, Josephine;Ouyang, Daniel;Yeung, Vincent 25
Background: This study analyzed whether socio-economic factors affect the cause specific survival of soft tissue sarcoma (STS). Methods: Surveillance, Epidemiology and End Results (SEER) soft tissue sarcoma (STS) data were used to identify potential socio-economic disparities in outcome. Time to cause specific death was computed with Kaplan-Meier analysis. Kolmogorov-Smirnov tests and Cox proportional hazard analysis were used for univariate and multivariate tests, respectively. The areas under the receiver operating curve were computed for predictors for comparison. Results: There were 42,016 patients diagnosed STS from 1973 to 2009. The mean follow up time (S.D.) was 66.6 (81.3) months. Stage, site, grade were significant predictors by univariate tests. Race and rural-urban residence were also important predictors of outcome. These five factors were all statistically significant with Cox analysis. Rural and African-American patients had a 3-4% disadvantage in cause specific survival. Conclusions: Socio-economic factors influence cause specific survival of soft tissue sarcoma. Ensuring access to cancer care may eliminate the outcome disparities. -
Yu, Ting-Ting;Han, Zhi-Gang;Shan, Li;Tao, Jie;Zhang, Tao;Yuan, Shuai-Fei;Shen, Hong-Li 29
Background and Objective: Lung cancer is one of the malignant diseases which most seriously threat humansurvival and development. This study aimed to assess osteopontin (OPN) expression in non-small cell lung cancer (NSCLC) and any relationship with clinicopathological features. Methods: Immunohistochemistry was used to determine OPN expression and microvascular density (MVD) in 120 cases of NSCLC also undergoing clinical assessment. Results: Moderately positive expression of OPN was found in 34.6% (41/120) and strong expression in 47.5% (57/120) of the NSCLCs; OPN expression in carcinomas was higher than in pericarcinoma tissues (P<0.05). While no obvious association was observed with NSCLC patient age, gender, maximum diameter of the tumor and pathological type, OPN expression was more commonly detected in poorly differentiated carcinoma tissue and lymph node metastasis as well as at advanced clinical stage (P<0.05); OPN expression in cancer tissue was positively correlated with MVD (r = 0.839, P = 0.000). Conclusion: OPN plays an important role in promoting tumor angiogenesis and progress of NSCLCs and has the possibility to become the new target for therapy. -
Larijani, Leila;Madjd, Zahra;Samadikuchaksaraei, Ali;Younespour, Shima;Zham, Hanieh;Rakhshan, Azadeh;Mohammadi, Foruzan;Rahbari, Ali;Moradi, Afshin 33
Background: Meningiomas are the second most common primary intracranial tumors after gliomas. Epigenetic biomarkers such as DNA methylation, which is found in many tumors and is thus important in tumorigenesis can help diagnose meningiomas and predict response to adjuvant chemotherapy. We investigated aberrant O6-methyl guanine methyltransferase (MGMT) methylation in meningiomas. Materials and Methods: Sixty-one patients were classified according to the WHO grading, and MGMT promoter methylation status was examined via the methylation-Specific PCR(MSP) method. Results: MGMT promoter methylation was found in 22.2% of grade I, 35% of grade I with atypical features, 36% of grade II, and 42.9% of grade III tumors. Conclusions: There was an increase, albeit not statistically significant, in MGMT methylation with a rise in the tumor grade. Higher methylation levels were also observed in the male gender. -
Yaw, Yong Heng;Shariff, Zalilah Mohd;Kandiah, Mirnalini;Weay, Yong Heng;Saibul, Nurfaizah;Sariman, Sarina;Hashim, Zailina 39
Background: This study aimed to provide an overview of lifestyle changes after breast cancer diagnosis and to examine the relationship between dietary and physical activity changes with weight changes in breast cancer patients. Women with breast carcinomas (n=368) were recruited from eight hospitals and four breast cancer support groups in peninsular Malaysia. Dietary and physical activity changes were measured from a year preceding breast cancer diagnosis to study entry. Mean duration since diagnosis was$4.86{\pm}3.46$ years. Dietary changes showed that majority of the respondents had decreased their intake of high fat foods (18.8-65.5%), added fat foods (28.3-48.9%), low fat foods (46.8-80.7%), red meat (39.7%), pork and poultry (20.1-39.7%) and high sugar foods (42.1-60.9%) but increased their intake of fish (42.7%), fruits and vegetables (62.8%) and whole grains (28.5%). Intake of other food groups remained unchanged. Only a small percentage of the women (22.6%) had increased their physical activity since diagnosis where most of them (16.0%) had increased recreational activities. Age at diagnosis (${\beta}$ = -0.20, p= 0.001), and change in whole grain (${\beta}$ = -0.15, p= 0.003) and fish intakes (${\beta}$ = 0.13, p= 0.013) were associated with weight changes after breast cancer diagnosis. In summary, the majority of the women with breast cancer had changed their diets to a healthier one. However, many did not increase their physical activity levels which could improve their health and lower risk of breast cancer recurrence. -
Lin, Chen;Huang, Fei;Zhang, Ya-Jing;Tuokan, Talafu;Kuerban, Gulinaer 45
Aims: Early diagnosis is important for cervical cancer treatment. This study aimed to characteriz the microRNA profile and target gene protein levels of cervical cancers in Uygur women for application in early diagnosis. Methods: The profiles of miRNA in cervical cancer and chronic cervicitis were analyzed with miRNAmicroarray V4.0. The expression of miR-101 was detected by real-time PCR and locked nucleotide acid in situ hybridization (LNA-ISH). Cox-2 protein levels were assessed by immunohistochemistry. Results: The microarray identified a set of 12 miRNAs significantly decreased in cervical cancer in comparison to the control group. Quantitative RT-PCR analysis showed miR-101 to be significantly downregulated in cancer tissues (p<0.05) while LNA-ISH showed miR-101 positive rates of 80% (20/25) and 8% (5/25) (p<0.05) in the control and cervical cancer groups. Cox-2 positive rates of cervical cancer and control groups were 84% (21/25) and 8% (2/25) (p<0.05). Conclusions: Use of down-regulation of miR-101 and up-regulation of Cox-2 as markers may play a role in early diagnosis of cervical cancer in Uygur women. -
Davaran, Soodabeh;Alimirzalu, Samira;Nejati-Koshki, Kazem;Nasrabadi, Hamid Tayefi;Akbarzadeh, Abolfazl;Khandaghi, Amir Ahmad;Abbasian, Mojtaba;Alimohammadi, Somayeh 49
Background: Hydrogels are a class of polymers that can absorb water or biological fluids and swell to several times their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogel nanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled actuation. Materials and Methods: In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied. At first, magnetic nanoparticles ($Fe_3O_4$ ) with an average size 10 nm were prepared. At second approach, thermo and pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAA-VP) were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values (pH=5.8, pH=7.4) at$37^{\circ}C$ . Magnetic iron oxide nanoparticles ($Fe_3O_4$ ) and doxorubicin were incorporated into copolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures. Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogel nanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy (SEM). Results: The results indicated that drug loading efficiency was increased by increasing the drug ratio to polymer. Doxorubicin was released more at$40^{\circ}C$ and in acidic pH compared to that$37^{\circ}C$ and basic pH. Conclusions: This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite could be an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitive properties. -
Ozkan-Gurdal, Sibel;Cabioglu, Neslihan;Ozcinar, Beyza;Muslumanoglu, Mahmut;Ozmen, Vahit;Kecer, Mustafa;Yavuz, Ekrem;Igci, Abdullah 55
Background: Whether sentinel lymph node biopsy (SLNB) should be performed in patients with pure ductal carcinoma in situ (DCIS) of the breast has been a question of debate over the last decade. The aim of this study was to identify factors associated with microinvasive disease and determine the criteria for performing SLNB in patients with DCIS. Materials and Methods: 125 patients with DCIS who underwent surgery between January 2000 and December 2008 were reviewed to identify factors associated with DCIS and DCIS with microinvasion (DCISM). Results: 88 patients (70.4%) had pure DCIS and 37 (29.6%) had DCISM. Among 33 DCIS patients who underwent SLNB, one patient (3.3%) was found to have isolated tumor cells in her biopsy, whereas 1 of 14 (37.8%) patients with DCISM had micrometastasis (7.1%). Similarly, of 16 patients (18.2%) with pure DCIS and axillary lymph node dissection (ALND) without SLNB, none had lymph node metastasis. Furthermore, of 20 patients with DCISM and ALND, only one (5%) had metastasis. In multivariate analysis, the presence of comedo necrosis [relative risk (RR)=4.1, 95% confidence interval (CI)=1.6-10.6, P=0.004], and hormone receptor (ER or PR) negativity (RR=4.0, 95%CI=1.5-11, P=0.007), were found to be significantly associated with microinvasion. Conclusions: Our findings suggest patients presenting with a preoperative diagnosis of DCIS associated with comedo necrosis or hormone receptor negativity are more likely to have a microinvasive component in definitive pathology following surgery, and should be considered for SLNB procedure along with patients who will undergo mastectomy due to DCIS. -
Hung, Yu-Shin;Chou, Wen-Chi;Chen, Tai-Di;Chen, Tse-Ching;Wang, Po-Nan;Chang, Hung;Hsu, Hung-Chih;Shen, Wen-Chi;Cheng, Wei-Hong;Chen, Jen-Shi 61
Background: Solid cancers with bone marrow metastases are rare but lethal. This study aimed to identify clinical factors predictive of survival in adult patients with solid cancers and bone marrow metastases. Methods: A total of 83 patients were enrolled consecutively between January 1, 2000 and December 31, 2012. Bone marrow metastases were confirmed by biopsies. Patient clinical features and laboratory data were analyzed for associations. Results: The median age of the patients was 54 years (range, 23-88 years), and 58% were male. The 3 most common primary tumor locations were the stomach (32 patients, 39%), prostate (16 patients, 19%), and lungs (12 patients, 15%). The median overall survival was 49 days (range, 3-1423 days). Patients with Eastern Cooperative Oncology Group performance status 1, cancers of prostate origin, platelet counts over 50,000/ml, and undergoing antitumor therapies had a significantly better prognosis in the multivariate analysis. The median survival times were 173 and 33 days for patients with 2-3 more favorable parameters (n=24) and those with 0-1 (n=69), respectively (hazard ratio 0.30; 95% CI 0.17-0.52, p<0.001). Conclusions: Solid cancers with bone marrow metastases are dismal and incurable diseases. Understanding prognostic factors to these diseases helps medical personnel to provide appropriate treatments and better inform patients about outcomes. Antitumor therapies may improve outcomes in selected patient cohorts. -
Mu, Xiao-Yan;Dong, Xue-Li;Sun, Jie;Ni, Yu-Hua;Dong, Zhang;Li, Xi-Li;Sun, Er-Lian;Yi, Zhou;Li, Gao 69
The effects of erlotinib combined with celecoxib in a lung cancer xenograft model were here explored with a focus on possible mechanisms. A xenotransplanted lung cancer model was established in nude mice using the human lung cancer cell A549 cell line and animals demonstrating tumour growth were randomly divided into four groups: control, erlotinib, celecoxib and combined (erotinib and celecoxib). The tumor major axis and short diameter were measured twice a week and after 40 days tissues were collected for immunohistochemical analyses of Bcl-2 and Bax positive cells and Western-blotting analyses for the epidermal growth factor recepto (EGFR), P-EGFR, and cyclooxygenase-2 (COX-2). Tumor size in the combined group was smaller than in the others (p<0.01) and the percentage of Bcl-2 positive cells was fewer in most cases (p<0.01), while that of Bax positive cells was greater than in the erlotinib and celecoxib groups (P>0.05). Western blotting showed decreased expression of P-EGFR and COX-2 with both erlotinib and celecoxib treatments, but most pronouncedly in the combined group (P<0.05). Simultaneous blockage of the EGFR and COX-2 signal pathways exerted stronger growth effects in our human xenotransplanted lung cancer model than inhibition of either pathway alone. The anti-tumor effects were accompanied by synergetic inhibition of tumor cell apoptosis, activation of p-EGFR and expression of COX-2. -
Bodoor, Khaldon;Haddad, Yazan;Alkhateeb, Asem;Al-Abbadi, Abdullah;Dowairi, Mohammad;Magableh, Ahmad;Bsoul, Nazzal;Ghabkari, Abdulhameed 75
Aberrant DNA methylation of tumor suppressor genes has been reported in all major types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. However, most of the previous reports did not show the extent of concurrent methylation of multiple genes in the four leukemia types. Here, we analyzed six key genes (p14, p15, p16, p53, DAPK and TMS1) for DNA methylation using methylation specific PCR to analyze peripheral blood of 78 leukemia patients (24 CML, 25 CLL, 12 AML, and 17 ALL) and 24 healthy volunteers. In CML, methylation was detected for p15 (11%), p16 (9%), p53 (23%) and DAPK (23%), in CLL, p14 (25%), p15 (19%), p16 (12%), p53 (17%) and DAPK (36%), in AML, p14 (8%), p15 (45%), p53 (9%) and DAPK (17%) and in ALL, p15 (14%), p16 (8%), and p53 (8%). This study highlighted an essential role of DAPK methylation in chronic leukemia in contrast to p15 methylation in the acute cases, whereas TMS1 hypermethylation was absent in all cases. Furthermore, hypermethylation of multiple genes per patient was observed, with obvious selectiveness in the 9p21 chromosomal region genes (p14, p15 and p16). Interestingly, methylation of p15 increased the risk of methylation in p53, and vice versa, by five folds (p=0.03) indicating possible synergistic epigenetic disruption of different phases of the cell cycle or between the cell cycle and apoptosis. The investigation of multiple relationships between methylated genes might shed light on tumor specific inactivation of the cell cycle and apoptotic pathways. -
Guan, Yan-Ping;Yang, Xue-Xi;Yao, Guang-Yu;Qiu, Fei;Chen, Jun;Chen, Lu-Jia;Ye, Chang-Sheng;Li, Ming 85
Background: Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations. Methods: Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status. Results: Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status. Conclusion: In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before utilization of these loci in Chinese. -
Gopal, Priya Kalyan;Paul, Mausumi;Paul, Santanu 93
Background: Curcumin has has been reported to exert anti-inflammatory, anti-oxidation and anti-angiogenic activity in various types of cancer. It has also been shown to induce apoptosis in leukemia cells. We aimed to unravel the role of the redox pathway in Curcumin mediated apoptosis with a panel of human leukemic cells. Materials and Methods: In this study in vitro cytotoxicity of Curcumin was measured by MTT assay and apoptotic effects were assessed by annexin V/PI, DAPI staining, cell cycle analysis, measurement of caspase activity and PARP cleavage. Effects of Curcumin on intracellular redox balance were assessed using fluorescent probes like$H_2DCFDA$ , JC1 and an ApoGSH Glutathione Detection Kit respectively. Results: Curcumin showed differential anti-proliferative and apoptotic effects on different human leukemic cell lines in contrast to minimal effects on normal cells. Curcumin induced apoptosis was associated with the generation of intracellular ROS, loss of mitochondrial membrane potential, intracellular GSH depletion, caspase activation. Conclusions: As Curcumin induces programmed cell death specifically in leukemic cells it holds a great promise as a future therapeutic agent in the treatment of leukemia. -
Chen, Wen-Ting;Gao, Xiang;Han, Xiao-Dian;Zheng, Hui;Guo, Lin;Lu, Ren-Quan 101
Background and Purpose: Human epididymis protein 4 (HE4) has been suggested to be a novel biomarker of epithelial ovarian cancer (EOC). The present study aimed to evaluate and compare HE4 with the commonly used marker, carbohydrate antigen 125 (CA125), in prediction and therapy-monitoring of EOC. Patients and Methods: Serum HE4 concentrations from 123 ovarian cancer patients and 174 controls were measured by Roche electrochemiluminescent immunoassay (ECLIA). Risk of ovarian malignancy algorithm (ROMA) values were calculated and assessed. In addition, the prospects of HE4 detection for therapy-monitoring were evaluated in EOC patients. Results: The ROMA score could classify patients into high- and low-risk groups with malignancy. Indeed, lower serum HE4 was significantly associated with successful surgical therapy. Specifically, 38 patients with EOC exhibited a greater decline of HE4 compared with CA125. In contrast, elevation of HE4 better predicted recurrence (of 46, 11 patients developed recurrence, and with it increased HE4 serum concentrations) and a poor prognosis than CA125. Conclusions: This study suggests that serum HE4 levels are closely associated with outcome of surgical therapy and disease prognosis in Chinese EOC patients. -
Madhivanan, Purnima;Srinivas, Vijaya;Marlow, Laura;Mukherjee, Soumyadeep;Narayanappa, Doddaiah;Mysore, Shekar;Arun, Anjali;Krupp, Karl 107
Background: Increasing uptake of human papillomavirus (HPV) vaccine should be a priority in developing countries since they suffer 88% of the world's cervical cancer burden. In many countries studies show that age at vaccination is an important determinate of parental acceptability. This study explores parental preferences on age-to-vaccinate for adolescent school-going girls. Materials and Methods: The sample was selected using a two-stage probability proportional to size cluster sampling methodology. Questionnaires were sent home with a random sample of 800 adolescent girls attending 12 schools in Mysore to be completed by parents. Descriptive statistics including frequencies, percentages and proportions were generated for independent variables and bivariate analyses (Chi square test) were used to assess the relationship between independent and appropriate age-to-vaccinate. Results: HPV vaccination acceptability was high at 71%. While 5.3% of parents felt girls should be vaccinated by 10 years or younger; 38.3% said 11-15 years; 14.8% said 16-18 years; 5.8% suggested over 19 years; and 33% didn't know. Only 2.8% of parents would not vaccinate their daughters. Conclusions: Delaying HPV vaccination until later ages may signifivantly increase uptake of the HPV vaccine in India. -
Objective: To study potential targets of Danshensu via dual inverse docking. Method: PharmMapper and idTarget servers were used as tools, and the results were checked with the molecular docking program autodock vina in PyRx 0.8. Result: The disease-related target HRas was rated top, with a pharmacophore model matching well the molecular features of Danshensu. In addition, docking results indicated that the complex was also matched in terms of structure, H-bonds, and hydrophobicity. Conclusion: Dual inverse docking indicates that HRas may be a potential anticancer target of Danshensu. This approach can provide useful information for studying pharmacological effects of agents of interest.
-
Cabuk, Devrim;Basaran, Gul;Teomete, Mehmet;Dane, Faysal;Korkmaz, Taner;Seber, Selcuk;Telli, Ferhat;Yumuk, Perran Fulden;Turhal, Serdar 117
Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. Materials and Methods: We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively Results: A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). Conclusions: All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature. -
Li, Da-Ke;Han, Jing;Liu, Ji-Bin;Jin, Guang-Fu;Qu, Jun-Wei;Zhu, Meng;Wang, Yan-Ru;Jiang, Jie;Ma, Hong-Xia 123
A recent study summarized several published genome-wide association studies (GWASs) of cancer and reported two pleiotropic loci at 6p21.1 and 7p15.3 contributing to multiple cancers including lung cancer, noncardia gastric cancer (NCGC), and esophageal squamous-cell carcinoma (ESCC) in Han Chinese. However, it is not known whether such genetic variants have similar effects on the risk of gynecologic cancers, such as ovarian cancer. Hence, we explored associations between genetic variants in 6p21.1 and 7p15.3 and ovarian cancer risk in Han Chinese women. We performed an independent case-control study by genotyping the two loci (rs2494938 A > G at 6p21.1 and rs2285947 A > G at 7p15.3) in a total of 377 ovarian cancer cases and 1,034 cancer-free controls using TaqMan allelic discrimination assay. We found that rs2285947 at 7p15.3 was significantly associated with risk of ovarian cancer with per allele odds ratio (OR) of 1.33 [95% confidence interval (CI): 1.08-1.64, P=0.008]. However, no significant association was observed between rs2494938 and ovarian cancer risk. Our results showed that rs2285947 at 7p15.3 may also contribute to the development of ovarian cancer in Han Chinese women, further suggesting pleiotropy of 7p15.3 in multiple cancers. -
Alipour, Sadaf;Hadji, Maryam;Hosseini, Ladan;Omranipour, Ramesh;Saberi, Azin;Seifollahi, Akram;Bayani, Leila;Shirzad, Nooshin 129
Background: The true association between breast cancer and vitamin D is currently under investigation. We compared serum 25-hydroxy-vitamin D levels in women with benign and malignant breast masses and controls. Materials and Methods: Levels of vitamin D were measured by electrochemiluminescense. Serum levels >35 ng/ml, 25-35 ng/ml, 12.5-25 ng/ml and <12.5 ng/ml were considered as normal, mild, moderate and severe vitamin D deficiency, respectively. Results: Overall, 364 women were included in the control, 172 in the benign and 136 in the malignant groups. The median serum vitamin D level was significantly lower in breast cancers than controls. Levels were also lower in malignant than benign cases and in benign cases than controls although statistically non-significant. Conclusions: Multinomial logistic regression analysis showed that severe vitamin D deficiency causes a three-fold increase in the risk of breast cancer while this was not the case for moderate and mild deficiency. -
Fouladi, Nasrin;Ali-Mohammadi, Hossein;Pourfarzi, Farhad;Homaunfar, Nasrin 133
Background: Today, breast cancer is increasing in nearly all societies. Currently, cancers are the third leading cause of death in Iran after cardiovascular diseases and accidents. Of the cancers, breast cancer is spreading particularly rapidly among Iranian women. Negative effects of discontinuation of care on patient survival have been well documented. Inhibiting or facilitating factors affecting continuity of care at different stages of the patient care continuum should be identified. Materials and Methods: The current study implemented a qualitative method that provided tools to examine factors in detail. This study was conducted on 22 women, undergoing surgery and chemotherapy after being diagnosed with breast cancer. Content analysis was the technique adopted. Results: The effective factors in continuity of care from the patients' perception, based on the participant statements, were classified into three categories of evaluation of symptoms, psychological reactions, and care triggers with several subcategories. Conclusions: According to the outcomes of the current study, it can be noted that, the patient experiences can be brought into use by health-care professionals and assist them in providing patient sand their families with adequate consulting services. It can also provide an opportunity for making interventions tailored to the community culture, and closer adherence of patients to the prescribed treatments. -
Li, Yan;Miao, Li-Yun;Xiao, Yong-Long;Cai, Hou-Rong;Zhang, De-Ping 139
Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs$41.0{\pm}3.50%$ , P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549,$4.33{\pm}0.33$ vs$0.33{\pm}0.33$ , P=0.01; in SPC-A1,$2.67{\pm}0.33$ vs$0.00{\pm}0.00$ , P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (>$200{\times}10^9/L$ , 3 months versus${\leq}200{\times}10^9/L$ , 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC. -
Li, Ying-Jun;Zhang, Zhen-Yu;Mao, Ying-Ying;Jin, Ming-Juan;Jing, Fang-Yuan;Ye, Zhen-Hua;Chen, Kun 145
MicroRNAs (miRNAs) negatively regulate gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to digestive system cancers was inconsistent in previous studies. In this study, we conducted a literature search of PubMed to identify all relevant studies published before August 31, 2013. A total of 21 independent case-control studies were included in this updated meta-analysis with 9,558 cases and 10,614 controls. We found that the miR-146a rs2910164 polymorphism was significantly associated with decreased risk of digestive system cancers in an allele model (OR=0.90, 95%CI 0.87-0.94), homozygote model (OR=0.84, 95%CI 0.77-0.91), dominant model (OR=0.90, 95%CI 0.84-0.96), and recessive model (OR=0.85, 95%CI 0.79-0.91), while in a heterozygous model (OR = 0.99, 95% CI 0.89-1.11) the association showed marginal significance. Subgroup analysis by cancer site revealed decreased risk in colorectal cancer above allele model (OR=0.90, 95%CI 0.83-0.97) and homozygote model (OR=0.85, 95%CI 0.72-1.00). Similarly, decreased cancer risk was observed when compared with allele model (OR=0.87, 95%CI 0.81-0.93) and recessive model (OR=0.81, 95%CI 0.72-0.90) in gastric cancer. When stratified by ethnicity, genotyping methods and quality score, decreased cancer risks were also observed. This current meta-analysis indicated that miR-146a rs2910164 polymorphism may decrease the susceptibility to digestive system cancers, especially in Asian populations. -
Babacan, Nalan Akgul;Yucel, Birsen;Kilickap, Saadettin;Seker, Mehmet Metin;Kacan, Turgut;Olcas, Ilknur Koc;Eren, Ayfer Ay;Odabas, Hatice 151
Background: Lung cancer is the most common cause of cancer-related death worldwide. The incidence of lung cancer is aproximately 7-8 thousand percent in Turkish women. In this study, we aimed to evaluate the clinical, pathological properties and survival data of female patients with lung cancer who were treated in our center. Materials and Methods: From 2007 to 2012, 50 women with lung cancer were enrolled. Patient data were evaluated retrospectively. Results: The median age was 61 (40-81). Forty patients (80%) were diagnosed with non small cell lung cancer (NSCLC), 10 patients (20%) were small cell carcinoma (SCC). Twelve (24%) patients were smokers and 13 of 16 non-smokers had a history of exposure to asbestos. The most common histologic subtype was adenocarcinoma (46%) and this accounted for 71% in patients with exposure to asbestos. The most common initial Eastern Cooperative Oncology Group (ECOG) performance score was 1 (24 patients, 48%) and initial stage was IV (25 patients, 50%) in the study group. During the median 15 months (1-96 months) followup period: 1 year overall survival (OS) was 68%, 2year overall survival was 36% and the median survival time was 19 months. According to univariate analysis, poor ECOG performance status, advanced stage, anemia and weight loss at time of diagnosis were negative prognostic factors. However, adenocarcinoma sub-type was a positive prognostic factor. Conclusions: In this study NSCLC sub-type, poor ECOG performance score, advanced stage, anemia and weight loss were prognostic factors in Turkish women with lung cancer. -
Avci, Ilknur Aydin;Kumcagiz, Hatice;Altinel, Busra;Caloglu, Ayse 155
Purpose: This study aimed to analyse female academician health beliefs for breast cancer screening and levels of self-esteem. Materials and Methods: This cross-sectional study was conducted between October 2010 and March 2011, covering female academicians working in all faculties and vocational schools at Ondokuz Mayis University, except for the ones in the field of health (n=141). Data was collected using a questionnaire developed by researchers in the light of the related literature, the Champion's Health Belief Model Scale for Breast Cancer, and the Coopersmith Self-Esteem Inventory. Descriptive statistics, the t-test, Mann-Whitney U and correlation analysis were used to analyze the data with the SPSS 13.0 statistical package. Results: 53.8% of the participants were single, 58.6% did not have children, 80.7% had regular menstrual cycles, 28.3% was taking birth control pills, 17.9% were undergoing hormone therapy, 11% suffered breast problems, 8.3% had relatives with breast cancer, 78,6% knew about breast self-examination (BSE), 68.3% was performing BSE, 16.2% were performing BSE monthly, 17.9% had had mammograms, and 30.3% had undergone breast examinations conductedby physicians. The women who had breast physical examinations done by physicians had higher susceptibility, self-efficacy and health motivation, and fewer barriers to mammography than those who did not have breast physical examinations. Conclusions: There was a relationship between the female academician self-esteem and their perceived seriousness of breast cancer, perceived barriers to BSE and health motivation. Our Turksih female academicians had medium levels of self-esteem. -
Yao, Quan;Sun, Jian-Guo;Ma, Hu;Zhang, An-Mei;Lin, Sheng;Zhu, Cong-Hui;Zhang, Tao;Chen, Zheng-Tang 161
Lung cancer is the most common causes of cancer-related deaths worldwide, and a lack of effective methods for early diagnosis has greatly impacted the prognosis and survival rates of the affected patients. Tumor-initiating cells (TICs) are considered to be largely responsible for tumor genesis, resistance to tumor therapy, metastasis, and recurrence. In addition to representing a good potential treatment target, TICs can provide clues for the early diagnosis of cancer. MicroRNA (miRNA) alterations are known to be involved in the initiation and progression of human cancer, and the detection of related miRNAs in TICs is an important strategy for lung cancer early diagnosis. As Hsa-miR-155 (miR-155) can be used as a diagnostic marker for non-small cell lung cancer (NSCLC), a smart molecular beacon of miR-155 was designed to image the expression of miR-155 in NSCLC cases. TICs expressing CD133 and CD338 were obtained from A549 cells by applying an immune magnetic bead isolation system, and miR-155 was detected using laser-scanning confocal microscopy. We found that intracellular miR-155 could be successfully detected using smart miR-155 molecular beacons. Expression was higher in TICs than in A549 cells, indicating that miR-155 may play an important role in regulating bio-behavior of TICs. As a non-invasive approach, molecular beacons could be implemented with molecular imaging to diagnose lung cancer at early stages. -
Yang, Jian-Hong;Hu, Jia;Wan, Li;Chen, Li-Juan 167
Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore investigated the effects of barbigerone on all three in the B16F10 tumor model established in both zebrafish and mouse models, and explored underlying molecular mechanisms. In vitro, barbigerone inhibited B16F10 cell proliferation, survival, migration and invasion and suppressed human umbilical vascular endothelial cell migration, invasion and tube formation in concentration-dependent manners. In the transgenic zebrafish model, treatment with$10{\mu}M$ barbigerone remarkably inhibited angiogenesis and tumor-associated angiogenesis by reducing blood vessel development more than 90%. In vivo, barbigerone significantly suppressed angiogenesis as measured by H and E staining of matrigel plugs and CD31 staining of B16F10 melanoma tumors in C57BL/6 mice. Furthermore, it exhibited highly potent activity at inhibiting tumor growth and metastasis to the lung of B16F10 melanoma cells injected into C57BL/6 mice. Western blotting revealed that barbigerone inhibited phosphorylation of AKT, FAK and MAPK family members, including ERK, JNK, and p38 MAPKs, in B16F10 cells mainly through the MEK3/6/p38 MAPK signaling pathway. These findings suggested for the first time that barbigerone could inhibit tumor-angiogenesis, tumor growth and lung metastasis via downregulation of the MEK3/6/p38 MAPK signaling pathway. The findings support further investigation of barbigerone as a potential anti-cancer drug. -
Background: Resection rates of lung cancer are low in general and especially in countries like Nepal. Advanced stage at presentation and poor general condition of the patient are the usual causes. Materials and Methods: In this prospective observational study, one hundred cases of lung cancer who presented at the Thoracic Surgery Unit between October 2011 and October 2012 were included. Results: Those aged in the
$6^{th}$ and$7^{th}$ decades together accounted for 72/100 patients. The male to female ratio was 2:1. There was a mean-$29.2{\pm}14.2$ pack yrs smoking history with only five non-smokers. Seventy-six patients presented with locally advanced disease while 21 had metastases. Only three had local disease. The average time between onset of symptoms to first contact with a doctor was$2.3{\pm}5.3$ months (range: 0-35.6 months). Average time between first contact to referral was$50.4{\pm}65.7$ days (range-0-365). Only three patients were resected, one after neo-adjuvant chemotherapy. Advanced disease was the cause of unresectability in 95 cases. One of three patients with local disease had pulmonary functions allowing the warranted resection.$N_2$ disease with$T_{1-3}$ on CT scan was found in 47. Three of these patients underwent mediastinoscopy and all confirmed uninvolved$N_2$ . Conclusions: Lung resection rates in our center remain low. Late presentation leading to advanced disease and poor pulmonary reserves preclude resection in most cases. More liberal use of mediastinal staging and better assessment of pulmonary functions may allow us to improve resection rates. -
Meiyanto, Edy;Putri, Dyaningtyas Dewi Pamungkas;Susidarti, Ratna Asmah;Murwanti, Retno;Sardjiman, Sardjiman;Fitriasari, Aditya;Husnaa, Ulfatul;Purnomo, Hari;Kawaichi, Masashi 179
Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of$80{\mu}M$ ,$21{\mu}M$ , and$82{\mu}M$ respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF-kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation. -
Influence of loneliness on human survival has been established epidemiologically, but genomic research remains undeveloped. We identified 34 loneliness-associated genes which were statistically significant for high-lonely and low-lonely individuals. With the univariate Cox proportional hazards regression model, we obtained corresponding regression coefficients for loneliness-associated genes fo individual cancer patients. Furthermore, risk scores could be generated with the combination of gene expression level multiplied by corresponding regression coefficients of loneliness-associated genes. We verified that high-risk score cancer patients had shorter mean survival time than their low-risk score counterparts. Then we validated the loneliness-associated gene signature in three independent brain cancer cohorts with Kaplan-Meier survival curves (n=77, 85 and 191), significantly separable by log-rank test with hazard ratios (HR) >1 and p-values <0.0001 (HR=2.94, 3.82, and 1.78). Moreover, we validated the loneliness-associated gene signature in bone cancer (HR=5.10, p-value=4.69e-3), lung cancer (HR=2.86, p-value=4.71e-5), ovarian cancer (HR=1.97, p-value=3.11e-5), and leukemia (HR=2.06, p-value=1.79e-4) cohorts. The last lymphoma cohort proved to have an HR=3.50, p-value=1.15e-7. Loneliness-associated genes had good survival prediction for cancer patients, especially bone cancer patients. Our study provided the first indication that expression of loneliness-associated genes are related to survival time of cancer patients.
-
Wang, Bing;Liu, Shu-Zheng;Zheng, Rong-Shou;Zhang, Fang;Chen, Wan-Qing;Sun, Xi-Bin 191
The aim of this study was to examine the trend of ovary cancer incidence from 1999 to 2010 in China and predict the burden up to 2020. Crude incidence, age specific incidence and age-adjusted incidence rates were calculated. Joinpoint regression was performed to obtain estimated annual percentages and Bayesian age-period-cohort modeling was used to predict the incidence rate until the year 2020. In China, the crude rate of ovary cancer was 7.91/100,000 and the age-adjusted rate was 5.35/100,000 overall during period 1999-2010. The rates in urban regions were higher than in rural regions. A significant rising trend during 1999-2006 was followed by a drop during 2006-2010 in age-adjusted rates for urban females. In contrast, constant rise was observed in rural women. The decrease in ovary cancer of urban areas tended to be restricted to women aged 50 years and younger. In contrast, increases of ovary cancer in rural areas appeared in virtually all age groups. Although the age-adjusted incidence rate for ovary cancer was predicted to be reduced after year 2011, the crude rate was likely to be relative stable up to 2020. The burden of ovary cancer in China will continue to be relative stable due to the aging population. -
Acmaz, Gokhan;Aksoy, Huseyin;Albayrak, Evrim;Baser, Muruvet;Ozyurt, Sezin;Aksoy, Ulku;Unal, Dilek 195
Aim: To evaluate precancerous lesions such as hyperplasia and endometrial polyps in obese postmenopausal women. Materials and Methods: Women who were referred with abnormal uterine bleeding in postmenopausal period or the presence of endometrial cells on cervical cytology in our department were investigated. Anthropometric measurements such as height, weight, body mass index, waist/hip ratio and endometrial thickness were compared between a precancerous lesion (hyperplasia and endometrial polyp) group and a pathologically normal group. Results: We detected statistically significant thickening of endometrium in patients with precancerous lesions. Moreover patients with precancerous lesions had higher body mass index than the pathologically normal group. Conclusions: We found elevated precancerous lesion rates in overweight and obese women in the postmenopausal period, of interest given that the prevalence of obesity is increasing in most parts of the world. Although screening for endometrial cancer is not recommended for the general population, in high-risk populations like obese postmenopausal women, it may be very important. -
El Sharkawi, Fathia Zaky;El Shemy, Hany Abdelaziz;Khaled, Hussein Moustafa 199
Background: Rosuvastatine, doxazosin, repaglinide and oxcarbazepin are therapeutic drugs available in the market for the treatment of different diseases. Potential to display antitumor activities has also been suggested. The aim of the current study was to evaluate their in vitro effects on some human transformed cell lines. Materials and Methods: Cytotoxicity of the four drugs was tested in MCF-7, HeLa and HepG2 cells by the neutral red assay method and also the effect of rosuvastatine and doxazosin against Ehrlich Ascities Carcinoma Cells (EACC) by trypan blue assay. Results: Rosuvastatine exerted the greatest cytotoxic effect against HepG2 cells with an$IC_{50}$ value of$58.7{\pm}69.3$ ; in contrast doxazosin showed least activity with$IC_{50}=104.4{\pm}115.7$ . Repaglinide inhibited the growth of both HepG2 and HeLa cells with$IC_{50}$ values of$87.6{\pm}117.5$ and$89.3{\pm}119.5$ , respectively. Oxcarbazepine showed a potent cytotoxicity against both HeLa ($IC_{50}=19.4{\pm}43.9$ ) and MCF7 cancer cells (($IC_{50}=22{\pm}35.7$ ).On the other hand the growth of EACC was completely inhibited by doxazosine (100% inhibition) while rosuvastatine had weak inhibitory activity (11.6%). Conclusions: The four tested drugs may have cytotoxic effects against hepatic, breast and cervical carcinoma cells; also doxazosine may inhibit the growth of endometrial cancer cells. Further investigations in animals are needed to confirm these results. -
The outcomes of first-generation EGFR-TKIs (Gefitnib and Erlotinib) have shown great advantages over traditional treatment strategies in patients with non-small cell lung cancer (NSCLC), but unfortunately we have to face the situation that most patients still fail to respond in the long term despite initially good control. Up to now, the mechanism of acquired resistance to EGFR-TKIs has not been fully clarified. Herein, we sought to compile the available clinical reports in the hope to better understanding the subsequent treatment choices, particularly on whether restoring after a drug holiday or switching to another EGFR-TKI is the better option after failure of one kind of EGFR-TKI.
-
Yu, Xiu-Wen;Xu, Qian;Xu, Ying;Gong, Yue-Hua;Yuan, Yuan 215
Objective: To determine the expression of E-cadherin,${\beta}$ -catenin, and transcription factor 4 (TCF4) proteins in gastric diseases with relation to Helicobacter pylori infection. Methods: A total of 309 patients including 60 with superficial gastritis (SG), 57 with atrophic gastritis (AG) and 192 with gastric cancer (GC), were enrolled. The expression of E-cadherin,${\beta}$ -catenin, TCF4 proteins in the gastric mucosa was detected by immunohistochemistry and H. pylori infection by immunohistochemistry and PCR. Results: The expression rates of E-cadherin were significantly higher in SG and AG than in GC (P<0.01), while those of${\beta}$ -catenin in the nucleus were significantly lower in SG and AG than in GC (P<0.05). In GC cases, the expression rates of E-cadherin,${\beta}$ -catenin and TCF4 were significantly higher in the intestinal type than in the diffuse type (P<0.05). In GC patients, the expression rate of E-cadherin was significantly higher in the presence of H. pylori than in the absence of infection (P=0.011). Moreover, the expression level of TCF4 and${\beta}$ -catenin protein was significantly higher in the nucleus and cytoplasm in H. pylori positive than in H. pylori negative GC patients, especially in those with the intestinal type (all P < 0.05). Conclusion: The expression of E-cadherin and${\beta}$ -catenin progressively decreases during the process of GC tumorigenesis, while overexpression of TCF4 occurs. H. pylori infection is associated with a significant increase in the expression of E-cadherin and${\beta}$ -catenin in the cytoplasm and nucleus in GC patients, especially those with the intestinal type. -
Abdulateef, Nahla Ahmad Bahgat;Ismail, Manar Mohammad;Aljedani, Hanadi 221
Background: Aberrant phenotypes in acute leukemia have variable frequency and their prognostic and predictive relevance is controversial, despite several reports of clinical significance. Aims: To determine the prevalence of aberrant antigen expression in acute leukemia, assess clinical relevance and demonstrate immunophenotype-karyotype correlations. Materials and Methods: A total of 73 (40 AML and 33 ALL) newly diagnosed acute leukemia cases presenting to KAMC, Kingdom of Saudi Arabia, were included. Diagnosis was based on WHO criteria and FAB classification. Immunophenotyping by flow cytometry, conventional karyotyping and fluorescence in situ hybridization for gene rearrangements were performed. Results: Aberrant antigens were detected in 27/40 (67.5%) of AML and in 14/33 (42.4%) in ALL cases. There were statistically significant higher TLC in Ly+ AML than in Ly-AML (p=0.05) and significant higher blast count in ALL with aberrant antigens at presentation and day 14 (p=0.005, 0.046). There was no significant relation to clinical response, relapse free survival (RFS) or overall survival (p>0.05), but AML cases expressing${\geq}2$ Ly antigens showed a lower median RFS than those expressing a single Ly antigen. In AML, CD 56 was expressed in 11/40. CD7 was expressed in 7/40, having a significant relation with an unfavorable cytogenetic pattern (p=0.046). CD4 was expressed in 5/40. CD19 was detected in 4/40 AML associated with M2 and t (8; 21). In ALL cases, CD33 was expressed in 7/33 and CD13 in 5/33. Regarding T Ag in B-ALL CD2 was expressed in 2 cases and CD56 in 3 cases. Conclusions: Aberrant antigen expression may be associated with adverse clinical data at presentation. AML cases expressing${\geq}2$ Ly antigens may have shorter median RFS. No specific cytogenetic pattern is associated with aberrant antigen expression but individual antigens may be related to particular cytogenetic patterns. Immunophenotype-karyotype correlations need larger studies for confirmation. -
Saleh, Amyza;Kong, Yink Heay;Vengu, Nedunchelian;Badrudeen, Haja;Zain, Rosnah Binti;Cheong, Sok Ching 229
Background: Dentists are typically the first professionals who are approached to treat ailments within the oral cavity. Therefore they should be well-equipped in detecting suspicious lesions during routine clinical practice. This study determined the levels of knowledge on early signs and risk factors associated with oral cancer and identified which factors influenced dentist participation in prevention and early detection of oral cancer. Materials and Methods: A survey on dentists' knowledge and their practices in prevention and early detection of oral cancer was conducted using a 26-item self-administered questionnaire. Results and Conclusions: A response rate of 41.7% was achieved. The level of knowledge on early signs and risk habits associated with oral cancer was high and the majority reported to have conducted opportunistic screening and advised patients on risk habit cessation. Factors that influenced the dentist in practising prevention and early detection of oral cancer were continuous education on oral cancer, age, nature of practice and recent graduation. Notably, dentists were receptive to further training in the area of oral cancer detection and cessation of risk habits. Taken together, the study demonstrated that the dental clinic is a good avenue to conduct programs on opportunistic screening, and continuous education in these areas is necessary to adequately equip dentists in running these programs. Further, this study also highlighted knowledge deficits and practice shortcomings which will help in planning and developing programs that further encourage better participation of dentists in prevention and early detection of oral cancer. -
Zhang, Zhi-Guo;Li, Gang;Feng, Da-Yun;Zhang, Jian;Zhang, Jing;Qin, Huai-Zhou;Ma, Lian-Ting;Gao, Guo-Dong;Wu, Lin 239
Several recent studies have showed that the n-myc downstream regulated gene 2 (NDRG2) is a new tumor suppressor gene, and that it plays an important role in tumor suppression in several cancers or cancer cell lines. However, few studies focused on its function in neuroblastoma cells. In the present investigation, we demonstrated that NDRG2 overexpression inhibited their proliferation. Using a cDNA microarray, we found that overexpression of NDRG2 inhibited the expression of cysteine-rich protein 61 (CYR61), a proliferation related gene. From our research, CYR61 may partially hinder NDRG2-mediated inhibition of cell proliferation. Overexpression of NDRG2 resulted in accumulation of cells in the G1 phase, which was accompanied by upregulation of p21 and p27 and downregulation of CDK4 and cyclin D1. Taken together, these data indicate that NDRG2 inhibits the proliferation of neuroblastoma cells partially through suppression of CYR61. Our findings offer novel insights into the physiological roles of NDRG2 in neuroblastoma cell proliferation, and NDRG2 may prove to be effective candidate for the treatment of children with neuroblastoma. -
Significance of Expression of Human METCAM/MUC18 in Nasopharyngeal Carcinomas and Metastatic LesionsLin, Jin-Ching;Chiang, Cheng-Feng;Wang, Shur-Wern;Wang, Wen-Yi;Kwan, Po-Cheung;Wu, Guang-Jer 245
Human METCAM/MUC18, a cell adhesion molecule (CAM) in the immunoglobulin-like gene super family, plays a dual role in the progression of several epithelium cancers; however, its role in the nasopharyngeal carcinoma (NPC) remains unclear. To initiate the study we determined human METCAM/MUC18 expression in tissue samples of normal nasopharynx (NP), NPCs, and metastatic lesions, and in two established NPC cell lines. Immunoblotting analysis was used for the determination in lysates of frozen tissues, and immunohistochemistry (IHC) for expression in formalin-fixed, paraffin-embedded tissue sections of 7 normal nasopharynx specimens, 94 NPC tissue specimens, and 3 metastatic lesions. Human METCAM/MUC18 was expressed in 100% of the normal NP, not expressed in 73% of NPC specimens (or expressed at very low levels in only about 27% of NPC specimens), and expressed again in all of the metastatic lesions. The level of human METCAM/MUC18 expression in NPC tissues was about one fifth of that in the normal NP and metastatic lesions. The low level of human METCAM/MUC18 expression in NPC specimens was confirmed by a weak signal of RT-PCR amplification of the mRNA. Low expression levels of human METCAM/MUC18 in NPC tissues were also reflected in the seven established NPC cell lines. These findings provided the first evidence that diminished expression of human METCAM/MUC18 is an indicator for the emergence of NPC, but increased expression then occurs with metastatic progression, suggesting that huMETCAM/MUC18, perhaps similar to TGF-${\beta}$ , may be a tumor suppressor, but a metastasis promoter for NPC. -
Inanc, Mevlude;Duran, Ayse Ocak;Karaca, Halit;Berk, Veli;Bozkurt, Oktay;Ozaslan, Ersin;Ozkan, Metin 253
Background: The standard treatment in the metastatic colorectal cancer consists of 5-FU based infusional regimens. However, with oral fluoropyrimidines, equal tumor responses may be obtained. Capecitabine causes macrocytosis of the cells by inhibition of DNA synthesis. In this context, a relationship was found between mean corpuscular volume (MCV) and response to therapy in breast cancer patients treated with Capecitabine, but whether this relationship also pertains in colorectal cancer has not been established. Materials and Methods: A total of 102 metastatic colorectal cancer patients treated with a oxaliplatin (XELOX)${\pm}$ Bevacizumab combination were retrospectively evaluated. Patients were randomized into three groups. Hematological parameters (MCV, MPV, PCT, PLT, NLR) were recorded retrospectively, before treatment and after 3 cycles of chemotherapy. Results: After three cycles of therapy, 20 (19.6%) patients had progressive disease (PD), 41 (40.1%) had stable disease (SD), and 41 (40.1%) demonstrated a partial response (PR). In 62 (60.7%) treatment was with capesitabin plus XELOX therapy, and in 40 (39.2%) it was XELOX-Bevacizumab combination therapy. There was no difference among three groups before the treatment in terms of MCV, MPV, PCT, PLT, and NLR. MCV showed significant increase in chemotherapy response groups (PR and SD). In addition, a significant decrease was observed for platelet count in chemotherapy response groups. While NLR decrease was seen in only a PR group, PCT decrease was observed in all three groups. PCT and PLT values were higher in patients receiving Bevacizumab. Conclusions: PLT, PCT, MPV, and NLR values were decreased due to Capecitabine-based chemotherapy, however MCV was increased. PCT and PLT values were higher in patients who received Bevacizumab than those who did not. MCV, PLT, and NLR can be considered as important factors in predicting response to colorectal carcinoma treatment. -
Kapahi, Ruhi;Manjari, Mridu;Sudan, Meena;Uppal, Manjit Singh;Singh, Neeti Rajan;Sambyal, Vasudha;Guleria, Kamlesh 257
Background: Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, has been implicated as a critical factor influencing tumor related angiogenesis. The aim of present study was to evaluate the relationship between VEGF +936C>T and +405C>G polymorphisms of VEGF with risk of breast cancer in Punjab, India. Materials and Methods: We screened DNA samples of 192 sporadic breast cancer patients and 192 unrelated healthy, gender and age matched control individuals for VEGF +936C>T and +405C>G polymorphisms using the PCR-RFLP method. Results: For the VEGF +405C>G polymorphism, we observed significantly increased frequency of GG genotype in cases as compared to controls and strong association of +405GG genotype was observed with three fold risk for breast cancer (OR=3.07; 95%CI 1.41-6.65; p=0.003). For the +936C>T polymorphism, significant associations of CT and combined CT+TT genotypes were observed with elevated risk of breast cancer (p=0.021; 0.023). The combined genotype combinations of GG-CC and GG-CT of +405C>G and +936C>T polymorphisms were found to be significantly associated with increased risk of breast cancer (p=0.04; 0.0064). Conclusions: The findings of the present study indicated significant associations of VEGF +936C>T and +405C>G polymorphisms with increased breast cancer risk in patients from Punjab, North India. -
Yuan, Chun-Hui;Yang, Xue-Qin;Zhu, Cheng-Liang;Liu, Shao-Ping;Wang, Bi-Cheng;Wang, Fu-Bing 265
Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functions and is essential for lymphocyte survival. While it known to induce differentiation and proliferation in some haematological malignancies, including certain types of leukaemias and lymphomas, little is known about its role in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhance the in vivo antitumor activity of tumor-reactive$CD8^+$ T cells with induction of IFN-${\gamma}$ in a murine breast cancer model. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then the recombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serum and intracellular IFN-${\gamma}$ levels were measured by ELISA and flow cytometry, respectively.$CD8^+$ T cell-mediated cytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantly inhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumor effect correlated with a marked increase in the level of IFN-${\gamma}$ and breast cancer cells-specific CTL cytotoxicity. In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of$CD8^+$ T cells from tumor bearing mice, while anti-IFN-${\gamma}$ blocked the function of$CD8^+$ T cells, suggesting that IFN-${\gamma}$ mediated the cytolytic activity of$CD8^+$ T cells. Furthermore, in vivo neutralization of$CD8^+$ T lymphocytes by CD8 antibodies reversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly through activating$CD8^+$ T cells and stimulating them to secrete IFN-${\gamma}$ in a murine breast tumor model. Based on these results, our study points to a potential novel way to treat breast cancer and may have important implications for clinical immunotherapy. -
Zhang, Tao;Chen, Hong-Sheng;Wang, Li-Feng;Bai, Ming-Han;Wang, Yi-Chong;Jiang, Xiao-Feng;Liu, Ming 273
Ellagic acid has been shown to inhibit tumor cell growth. However, the underlying molecular mechanisms remain elusive. In this study, our aim was to investigate whether ellagic acid inhibits the proliferation of MCF-7 human breast cancer cells via regulation of the TGF-${\beta}$ /Smad3 signaling pathway. MCF-7 breast cancer cells were transfected with pEGFP-C3 or pEGFP-C3/Smad3 plasmids, and treated with ellagic acid alone or in combination with SIS3, a specific inhibitor of Smad3 phosphorylation. Cell proliferation was assessed by MTT assay and the cell cycle was detected by flow cytometry. Moreover, gene expression was detected by RT-PCR, real-time PCR and Western blot analysis. The MTT assay showed that SIS3 attenuated the inhibitory activity of ellagic acid on the proliferation of MCF-7 cells. Flow cytometry revealed that ellagic acid induced G0/G1 cell cycle arrest which was mitigated by SIS3. Moreover, SIS3 reversed the effects of ellagic acid on the expression of downstream targets of the TGF-${\beta}$ /Smad3 pathway. In conclusion, ellagic acid leads to decreased phosphorylation of RB proteins mainly through modulation of the TGF-${\beta}$ /Smad3 pathway, and thereby inhibits the proliferation of MCF-7 breast cancer cells. -
Bhatti, Abu Bakar Hafeez;Ahmed, Irfan;Ghauri, Rashid Khan;Saeed, Qamar;Mir, Khurram 277
Background: Testicular cancer management is considered a marvel of modern science with excellent treatment results. Pakistan has a distinct ethnic variation and geographic distribution but data regarding clinical presentation of testicular tumors and their management is under reported. The objective of this study was to determine clinical profile, treatment modalities and survival outcome of testicular tumors in the Pakistani population. Materials and Methods: A retrospective review of patients who received treatment for testicular cancer at Shaukat Khanum Cancer Hospital from January 2009 to December 2012 was performed. Patient demographics, clinical features at presentation and treatment modalities were assessed. For categorical variables chi square test was used. Survival was calculated using Kaplan Meier survival curves and Log rank test was employed to determine significance. Results: The most common tumor was mixed germ cell tumor in 49% patients. For all tumor variants except seminoma, stage III was the most common clinical stage at presentation. Majority of patients with non seminomatous germ cell tumors presented in the15-30 year age group as compared to seminoma which was most prevalent in the 30-40 year age group. Orchiectomy followed by chemotherapy was the most common treatment modality in 80% patients. Expected 5 year survival for seminomas and non-seminomatous germ cell tumors was 96% and 90% respectively which was not significantly different (p=0.2). Conclusions: Despite a distinct clinical profile of testicular tumors in Pakistani population, survival is comparable with published reports. -
AL-Hashimi, Muzahem Mohammed Yahya;Wang, Xiang Jun 281
Background: Breast cancer is the most frequent malignancy of women worldwide. In Iraq, breast cancer ranks first among cancers diagnosed in women but no studies have been conducted on incidence trends. The present study of breast cancer in the country during 2000-2009 was therefore performed. Materials and Metbods: The registered data for breast cancer cases were collected from the Iraqi Cancer Registry/Ministry of Health. The significance of incidence rate trends during 2000-2009 was tested using Poisson regression. Age-standardized rates (ASR), and age-specific rates per 100,000 population were calculated. ResultS" A total of 23,792 incident breast cancer cases were registered among females aged${\geq}15$ years, represented 33.8% of all cancers in females registered during 2000-2009. It ranked first in all the years. The median age at diagnosis was 49 and the mean age was 52 years. The incidence rate of all female breast cancer in Iraq (all ages) increased from 26.6 per 100,000 in 2000 to 31.5 per 100,000 in 2009 (APC=1.14%, p<.0001). The incidence in age groups (40-49), (50-59) and (70+) increased in earlier years and has recently (2005-2009) become stable. The incidence in age group (60-69) did not decline since 2003, while the incidence rates in the age group (15-39) started to decline in 2004. Conclusions' With the Iraqi Cancer Registry data during the period 2000-2009, the incidence of all female breast cancer in Iraq (all ages) has risen. We found rapid increase in the age specific incidence rate among age group 60-69. However, breast cancer among Iraqi women still affects younger age groups than their counterparts in developed countries. Further epidemiological research is needed to examine possible causes and prevention measures. -
Objective: Genetic variation is considered to strongly impact on detoxification of carcinogens and therefore is related to cancer risk. However, findings for the null genotypes of GSTT1 and GSTM1 have not always been consistent. Therefore the present meta-analysis was conducted. Methods: We accessed the reported study at different research areas and used various databases, including PubMed and Wanfang Med Onlion from 1990 to May 1st 2013. We calculated the odds ratio (OR), 95% confidence interval (CI) and P value for oral cancer by using Review Manager 5.1 and STATE 12. Results: We found that there was no increased oral cancer risk among subjects carrying GSTM1 and GSTT1 null genotype (OR=1.35, 95%CI=0.68-2.68, P=0.39) and (OR=1.41, 95%CI=0.72-2.77, P=0.31) in the Chinese population. In contrast, in studies in India a significant correlation between GSTM1 null genotype and oral cancer was observed (OR=1.59, 95%CI=1.20-2.11, P=0.001), but not in GSTT1 (OR=1.21, 95% CI=0.84-1.74, P=0.31). Conclusion: We discovered that GSTM1 deletion polymorphism had a significant effect on the susceptibility of oral cancer in the Indian population.
-
Wang, Kai;Liu, Chao;Di, Chan-Juan;Ma, Cong;Han, Chun-Guang;Yuan, Mei-Ru;Li, Peng-Fei;Li, Lu;Liu, Yong-Xue 291
The radioprotective effects of a single administration of kojic acid (KA) against ionizing radiation were evaluated via assessment of 30-day survival and alterations of peripheral blood parameters of adult C57BL/6 male mice. The 30-day survival rate of mice pretreated with KA (75 or 300 mg/kg body weight, KA75 or KA300) subcutaneously 27 h prior to a lethal dose (8 Gy, 153.52 cGy/min) of gamma irradiation was higher than that of mice irradiated alone (40% or 60% vs 0%). It was observed that the white blood cell (WBC) count/the red blood cell (RBC) count, haemoglobin content, haematocrit and platelet count of mice with or without KA pretreatment as exposed to a sub-lethal dose (4 Gy, 148.14 cGy/min) of gamma irradiation decreased maximally at day 4/day 8 post-irradiation. Although the initial WBC values were low in KA300 or WR-2721 (amifostine) groups, they significantly recovered to normal at day 19, whereas in the control group they did not. The results from the cytotoxicity and cell viability assays demonstrated that KA could highly protect Chinese hamster ovary (CHO) cells against ionizing radiation with low toxicity. In summary, KA provides marked radioprotective effects both in vivo and in vitro. -
Khunluck, Tueanjai;Kukongviriyapan, Veerapol;Puapairoj, Anucha;Khuntikeo, Narong;Senggunprai, Laddawan;Zeekpudsa, Ponsilp;Prawan, Auemduan 299
Cholangiocarcinoma (CCA), a malignancy of biliary duct with a very poor prognosis, is the leading cause of cancer death in countries of the Mekong subregion. Liver fluke infection is the main etiological factor, but genetic variation has been recognized as also important in conferring susceptibility to CCA risk. Nuclear factor (erythroid derived 2)-like 2 (NRF2) is a key transcription factor in detoxification and antioxidant defense. Emerging evidence has demonstrated that genetic polymorphisms in the NRF2 gene may be associated with cancer development. The objectives of this study were to investigate the association of NRF2 genetic polymorphism with CCA risk and to evaluate the influence of the NRF2 genotype on survival time of affected patients. Single nucleotide polymorphisms (SNPs) of the NRF2 gene, including rs6726395: A/G, rs2886161: C/T, rs1806649: C/T, and rs10183914: C/T, were analyzed using TaqMan$^{(R)}$ SNP genotyping assays. Among 158 healthy northeastern Thai subjects, the allele frequencies were 41, 62, 94, and 92%, respectively. The correlation of NRF2 SNPs and CCA risk was analyzed in the 158 healthy subjects and 198 CCA patients, using unconditional logistic regression. The results showed that whereas the NRF2 SNPs were not associated with CCA risk (p>0.05), Kaplan-Meier analysis of 88 intrahepatic CCA patients showed median survival time with rs6726395 genotypes of GG and AA/AG to be$344{\pm}138$ (95%CI: 73-615) days and$172{\pm}37$ (95%CI: 100-244) days, respectively, (p<0.006). On multivariate Cox proportional hazard analysis, the GG genotype of rs6726395 was found to be associated with longer survival with a hazard ratio of 0.54 (95%CI: 0.31-0.94). In addition, non-papillary adenocarcinoma was associated with poor survival with a hazard ratio of 2.09 (95%CI: 1.16-3.75). The results suggest that the NRF2 rs6726395 polymorphism can be a potential prognostic biomarker for CCA patients. -
Aksan-Desteli, Guldeniz;Gursu, Turkan;Baykal, Cem Murat 305
Background: To investigate the indications of loop electrosurgical excision procedure (LEEP) and its overtreatment rates for the see and treat and three step strategies in cases of atypical squamous cells of undetermined cytology (ASC-US) and low grade intraepithelial neoplasia (LGSIL) cytology. Materials and Methods: We retrospectively analyzed colposcopy directed biopsy (CDB) and LEEP results of 176 paients with ASC-US or LGSIL cytologies who underwent colposcopic examination. Results: Initial cytologies were ASCUS in 120 women and LGSIL in 56. According to the see and treat approach immediate LEEP was performed for38 women. Among the remaining 138 women, LEEP was performed for 32 whose CDB results revealed CIN2/3 lesions. In the see and treat group the recognition of CIN2/3 was found to be 39.4%. The overtreatment rate was 60% as compared to 25% in the three step group. In CDB group detection of CIN 2 or greater lesions increased with 3 or more biopsies. Conclusions: In patients with ASC-US/LGSIL cytologies CDB should be performed before LEEP to prevent overtreatment, with attention to all suspected areas and more than 2 biopsies taken. -
Niu, Zhi-Min;Liang, Chun-Shui;Yu, Min;Wang, Yong-Sheng;Yu, Hai-Xia;Zhang, Qiong-Wen;Wei, Yu-Quan 309
Purpose: Cigarette smoking causes many kinds of cancer, and it is more closely related with lung cancer, rather than other cancers. Smoking is the leading cause of lung cancer and ninety percent of the smokers are male in China, but there is little published data concerning the psychological responses in the male smokers with lung cancer and its influence on the symptom burden. The aim of the study was to verify the hypothesis that male smokers with lung cancer have more positive attitude and less symptom burden, comparing to male non-smokers. Methods: A total of 194 men with cancer in West China Hospital, Sichuan, China, were assessed by self-administered questionnaire. Psychological response was measured by the Chinese version of Mini-Mental Adjustment to Cancer scale (Mini-MAC), and symptom burden was measured by the physical symptom distress scale from the Rotterdam Symptom Checklist (RSCL). Results: We found that smokers with lung cancer got higher scores in positive attitude and a smaller symptom burden than non-smokers. Patients with education lower than high school got higher scores of positive attitude compared to college graduate patients (p=0.038). Smokers with lung cancer who knew the potential carcinogenicity of cigarette showed less negative emotions (p=0.011). The psychological response was not affected by age, clinical stage, cell type, smoking duration and amount. Conclusions: Male smokers with lung cancer have a more positive attitude and fewer symptoms, comparing to male non-smokers. Appropriate psychological intervention for non-smokers with lung cancer deserves more attention. -
Jia, Wei-Juan;Jia, Hai-Xia;Feng, Hui-Yi;Yang, Ya-Ping;Chen, Kai;Su, Feng-Xi 315
Purpose: The purpose of this study was to investigate the recurrence pattern and characteristics of patients based on the 2013 St. Gallen surrogate molecular subtypes after breast-conserving surgery (BCS) in Chinese women. Methods: This retrospective analysis included 709 consecutive breast cancer patients undergoing BCS from 1999-2010 at our institution. Five different surrogate subtypes were created using combined expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) rates were calculated. Results: The 5-year LRRFS, DMFS, and DFS rates were 90.5%, 88.2%, and 81.5%, respectively. Multivariate analysis revealed that young age, node-positive disease, and HER2 enrichment were independent prognostic factors in LRRFS patients. There was also an independent prognostic role of lymph node-positive disease in DMFS and DFS patients. Patients with luminal A tumors had the most favorable prognosis, with LRRFS, DMFS, and DFS rates of 93.2%, 91.5%, and 87.4% at 5 years, respectively. Conversely, HER-2-enriched tumors exhibited the highest rate of locoregional recurrence (20.6%). Conclusion: Surrogate subtypes present with significant differences in RFS, DMFS, and LRRFS. Luminal A tumors have the best prognosis, whereas HER2-enriched tumors have the poorest. -
Liam, Chong-Kin;Leow, Hwong-Ruey;How, Soon-Hin;Pang, Yong-Kek;Chua, Keong-Tiong;Lim, Boon-Khaw;Lai, Nai-Lang;Kuan, Yeh-Chunn;Pailoor, Jayalakshmi;Rajadurai, Pathmanathan 321
Background: Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients. Materials and Methods: In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction. Results: EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94-18.17; p=0.002). Conclusions: In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations. -
Seker, Mehmet Metin;Kos, Tugba;Ozdemir, Nuriye;Seker, Ayse;Aksoy, Sercan;Uncu, Dogan;Zengin, Nurullah 327
Background: Ewing sarcoma is a small round cell tumor arising from soft tissue and bone that predominantly affects children and adolescents. The most unfavorable prognostic factor is the presence of distant metastasis at the time of diagnosis. Materials and Methods: The records of 26 Ewing sarcoma patients (14 male, 12 female) were re-evaluated retrospectively. Results: The median age was 26.5 (19-42) years. Eight patients (31%) showed a primary tumor in their extremities, 8 (31%) in the thorax, 4 (15%) at the vertebra, 4 (15%) in the head and neck, and 2 (8%) in the abdomen. Five patients (19%) had distant metastasis at diagnosis. The median progression-free survival was 72 months and 10 months in localized and metastatic disease, respectively (p=0.005). The overall survival rate was 19 months in metastatic disease, and the 5-year overall survival rate was 64% in localized disease (p=0.006). Patients who had localized disease in the extremities and were under age 30 had a favorable prognosis. Conclusions: Although Ewing sarcoma is a tumor affecting children and adolescents, it may be seen in adults, where the prognosis is generally worse. Although it is a highly malignant tumor, it is possible to achieve improved survival with combined modality treatments. -
Jiao, Feng;Yao, Li-Juan;Zhou, Jin;Hu, Hai;Wang, Li-Wei 331
There is a scarcity of reports addressing patients with multiple primary malignancies (MPM), especially for Chinese cses. The aim of this study was to present a detailed analysis of Chinese patients presenting with at least two primary malignancies. Particularly, the clinical characteristics and survival between synchronous and metachronous MPM were compared. Out of 6,545 cases, 72 patients (1.1%) including 39 males (54.2%) and 33 females (45.8%) were diagnosed as MPM, giving a male: female sex ratio of 1.2:1. Of these, there were 16 (22.2%) cases of synchronous MPM (7 males, 9 females), 55(76.4%) metachronous (31 males, 24 females), and 1 "mixed form". For first tumor diagnosis time, synchronous MPM patients generally presented later than the metachronous cases. The top three sites for malignancies with metachronous MPM were colorectum, head and neck, and lung, while for synchronous they were lung, colorectum and breast. Among MPM patients, the median survival time was 15.7 years and the 5-year survival was 56%, and there was statistical difference in MPM categories (P < 0.05). The median survival time was 17.3 years and 3.8 years for metachronous and synchronous MPM patients, respectively. In comparison with synchronous MPM patients, those metachronous had a longer survival. This studies increase understanding of the clinical features of Chinese MPM patients and suggest that those presenting with metachronous cancers have a higher incidence and a better prognosis. -
Oluka, Obiageli Crystal;Shi, Yan-Yan;Nie, Shao-Fa;Sun, Yi 335
Cancer is a menace fast gaining momentum in Nigeria and other developing countries. It is an expensive disease requiring a major financial and human resources for prevention, diagnosis and treatment. With no national policy on cancer control in the conntry, incidence (111.7/100,000 population) and mortality (86.6/100,000) rates in Nigeria are spiraling beyond control. This literature search study was primarily aimed at providing recommendations on cost-effective strategies for development interventions to promote self-management for cancer survivors in Nigeria with a goal to improve quality of life and overall survival. -
Baghel, Kavita;Kazmi, Hasan Raza;Raj, Saloni;Chandra, Abhijit;Srivastava, Rajeshwar Nath 343
Background: Maspin expression is a potential prognostic factor for various malignancies but its relation with gallbladder cancer is unknown and needs to be investigated needs to be investigated. We therefore here focused on maspin mRNA expression in normal, gall stone disease and gallbladder cancer subjects, with particular attention to prognostic importance in individuals with malignancies. Materials and Methods: This study was carried out at the Department of Surgical Gastroenterology, King George's Medical University, Lucknow, India. Gallbladder samples from normal (n=25), gall stone disease (n=25) and cancer patients (n=38) were analysed for maspin mRNA expression by semi-quantitative reverse transcriptase PCR and quantitative real time PCR. Statistical analysis was carried out using the Students t test or ANOVA. Survival analysis was conducted according to the Kaplan-Meier method and correlations were assessed using the Pearson correlation method. p<0.05 was considered statistically significant. Results: Significant increase (p=0.028) in expression of maspin mRNA was observed in gallbladder cancer as compared to gall stone disease, whereas no expression was found in normal tissues. Significant correlation (Pearson's coefficient(r)=-0.798, p<0.0001) was observed between relative quantification of maspin mRNA and survival of cancer patients after surgery, with significantly shorter (p=0.002) survival in patients having relative quantification >1.5 as compared to those having relative quantification <1.5. Similarly, significant differences in patient survival for maspin mRNA expression was observed for stage II (p=0.025) and III (p=0.011) cancer. Conclusions: Higher expression of maspin mRNA in gallbladder cancer has prognostic significance for stage II and III cancer, which needs to be investigated further. -
Background: Although previously studies have reported that most patients with malignancy prefer to die at home, this is not the real situation in clinical practice. Aim: In this study, we aimed to determine the characteristics of Turkish cancer patients admitted to the emergency department (ED) within one month before death. Materials and Method: This descriptive retrospective study focused on questions about how often and why patients with cancer visited the ED before death. A total of 107 individuals with cancer were divided into 2 groups: Group 1, patients with at least one visit in the final 4 weeks; and Group 2, patients with no visit to ED. Demographic and clinical features were compared between the two groups. Statistical analyses: Descriptive statistical methods, statistical analysis for correlation, Student's t-test, chi-square tests and logistic regression were used. Results: At least one visit to ED within one month before death was reported for 64 (60%) of the 107 cases. Of these 64 (Group 1), 38% (n=24) were discharged and 9% (n=6) died in the ED. The most common site of the primary tumor was the lung (n=24, 38%) and the most common symptom was dyspnea (92%). With the other 43 (40%) cancer patients not presenting to the ED within one month before death, they were more likely to be female with another type of cancer. Conclusions: Guidelines are needed for better management of cancer patients benefiting from visits to ED within the last month of life.
-
Wang, Cai-Xia;Wang, Xiang;Liu, Hai-Bai;Zhou, Zhi-Heng 355
Objective: Altered regulation of many transcription factors has been shown to play important roles in the development of leukemia. hMSH2 can modulate the activity of some important transcription factors and is known to be a regulator of hematopoietic differentiation. Herein, we investigated epigenetic regulation of hMSH2 and its influence on cell growth and overall survival of acute lymphoblastic leukemia (ALL) patients. Methods: hMSH2 promoter methylation status was assessed by COBRA and pyrosequencing in 60 ALL patients and 30 healthy volunteers. mRNA and protein expression levels of hMSH2, PCNA, CyclinD1, Bcl-2 and Bax were determined by real time PCR and Western blotting, respectively. The influence of hMSH2 on cell proliferation and survival was assessed in transient and stable expression systems. Results: mRNA and protein expression of hMSH2 and Bcl-2 was decreased, and that of PCNA, CyclinD1 and Bax was increased in ALL patients as compared to healthy volunteers (P<0.05). hMSH2 was inactivated in ALL patients through promoter hypermethylation. Furthermore, hMSH2 hypermethylation was found in relapsed ALL patients (85.7% of all cases). The median survival of patients with hMSH2 methylation was shorter than that of patients without hMSH2 methylation (log-rank test, P=0.0035). Over-expression of hMSH2 in cell lines resulted in a significant reduction in growth and induction of apoptosis. Conclusions: This study suggests that aberrant DNA methylation and epigenetic inactivation of hMSH2 play an important role in the development of ALL through altering cell growth and survival. -
Wang, Xin-Feng;Wu, Yan-Hua;Wang, Mao-Shui;Wang, Yun-Shan 363
Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), but not CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries. -
Haerian, Monir Sadat;Haerian, Batoul Sadat;Rooki, Hassan;Molanaei, Saadat;Kosari, Farid;Obohhat, Maedeh;Hosseinpour, Parisa;Azimzadeh, Pedram;Mohebbi, Seyed Reza;Akbari, Zahra;Zali, Mohammad Reza 369
Background: Colorectal cancer (CRC) is the fourth most common cause of cancer death in the world. Genetic variants in 8q24.21 including rs10505477 and rs6983267 have been hypothesized to be involved in susceptibility to CRC. This study aims to investigate the possible association between these loci and their haplotypes with CRC risk in Iranian population. Materials and Methods: Subjects were recruited from two hospitals in Tehran. The rs10505477 and rs6983267 polymorphisms were genotyped by TaqMan real time PCR using subject genomic DNA, extracted either from formalin-fixed, paraffin-embedded tissue of patients or from blood of the controls by standard methods. Results: A total of 715 subjects (380 CRC patients and 335 matched controls) were genotyped in this study. Allele and genotype analysis of the rs10505477 and rs6983267 polymorphisms by gender, age at diagnosis, tumor location, tumor grade, and tumor node metastasis (TNM) showed no significant association with CRC risk. There was a significant relationship between GG haplotype and susceptibility to age at diagnosis for both <60 and${\geq}60$ (p=0.0005 and p=0.000004, respectively) and between GT and CRC in the age at diagnosis${\geq}60$ (Table 3: p=0.031). The GG haplotype was less frequent in CRC patients with the age at diagnosis <60, but was more common in subjects with the age at diagnosis${\geq}60$ . Conclusions: Results of this study suggests that the rs6983267 and rs10505477 polymorphisms alone may not be relevant to CRC risk, but their GG haplotype plays a notable role in age at diagnosis of CRC in the Iranian population. -
Akan, Zafer;Baskurt, Busranur;Asliyuksek, Hizir;Kam, Erol;Yilmaz, Ahmet;Yuksel, Mehmet Bilgehan;Biyik, Recep;Esen, Ramazan;Koca, Dogan 375
This study examined the incidence rates of cancer cases (averages for 2006-2010) and relationships with environmental radioactivity levels. Soil and water samples were collected from provincial and district centers of Van city and the outdoor gamma doses were determined using a portable gamma scintillation detector. Gross alpha and beta, (226)Ra, (232)Th, and (40)K activities were measured in both tap water and soil samples. Although high rates of stomach and esophagus cancers have been reported previously in Van the underlying reasons have not hitherto been defined. Incidences of cancers were highest in the Gurpmar (326.0) and Ozalp (377.1) counties (p<0.001). As to the results of the gross alpha and gross beta radioactivity measurements in the drinking water, these two counties also had high beta radionuclide levels: Gurpmar ($140mBq/dm^3$ ) and Ozalp ($206mBq/dm^3$ ). Even if within the normal range, a relation between the higher rate of the incidence of stomach and esophagus cancers with that of the higher rate of beta radionuclide activity was clear. On Spearman correlation analysis, the relation between higher beta radionuclide levels and cancer incidence was found to be statistically significant (p<0.01). According to the results of the analysis, Van residents receive an average 1.86 mSv/y annual dose from outdoor gamma radiation, ingestion of radionuclides in the drinking water, and indoor$^{222}Rn$ activity. Moreover, gross alpha and beta activities were found to be extremely high in all of the lakes around the city of Van, Turkey. Further investigations with long-term detailed environmental radiation measurements are needed regarding the relationship between cancer cases and environmental radioactivity in the city of Van. -
Kaba, Mehmet;Pirincci, Necip;Benli, Erdal;Gecit, Ilhan;Gunes, Mustafa;Yuksel, Mehmet Bilgehan;Tok, Adem;Kemik, Ahu Sarbay 381
Background: Evidence indicates that Dickkopf-1 (DKK-1) levels may be a biomarker for cancer risk. The aim of this study was to assess DKK-1 and its correlation with clinic-pathological features in patients with bladder cancer. Materials and Methods: DKK-1 levels were determined in serum samples from 90 patients with bladder cancer before transurethral tumor resection. The concentrations of DKK-1 were determined by using enzyme linked immune-sorbent assay (ELISA). Results: Elevated preoperative DKK-1 levels were associated with tumor stage (p<0.001), grade (p<0.001) and histological grade (p<0.001). Conclusions: The results of our study demonstrated that the level of serum DKK-1 is correlated with both disease progression and increase in the tumor grade. Preoperative serum DKK-1 elevation may thus represent a novel marker for the determination of bladder cancer and the detection of patients with a likely poor clinical outcome. -
Al-Hashimi, Muzahem Mohammed Yahya;Wang, Xiang Jun 385
Background: Lung cancer is the most frequent malignancy of men worldwide. In Ninawa in Iraq, lung cancer ranks first among cancers diagnosed in men. Since no prior studies have been conducted on incidence trends in our population the present investigation of rates during 2000-2010 was therefore performed. Materials and Methods: Registy data for lung cancer cases were collected from the Directorate of Health in Ninawa-Mosul Continuing Medical Education Center. We restricted our analyses to men categorized according to the age groups of 0- 39, 40-49, 50-59, 60-69 and 70+ years. The significance of incidence rate trends during 2000-2010 was tested using Poisson regression. Age-standardized rates (ASR), and age-specific rates per 100,000 population were calculated. Results: A total of 1,206 incident lung cancer were registered among males, accounting for 15.5% of all male cancers registered during 2000-2010. It ranked first throughout the period. Median age at diagnosis was 69 (mean$66.8{\pm}11.0$ ) years. The incidence rate of all male lung cancers in Ninawa (all ages) decreased from 26.4 per 100,000 in 2000 to 12.7 in 2010 (APC=-6.55%, p<.0001). The incidences in age groups 40-49, 50-59, 60-69 and 70+ decreased in earlier years and recently appeared (2007-2010) stable. The incidence in age group (0-39) remained stable between 2000-2010. Squamous cell carcinoma (SCC)was the most common type of lung cancer, while adenocarcinoma was relatively rare. Conclusions: With the data from Directorate of Health in Ninawa during the period 2000-2010, lung cancer is the most common cancer but generally declining. Among all age groups, the recent incidence of lung cancer remained stable. The SCC predominance suggests change in tobacco habits as an important factor in the trends observed. -
Yamada, Ikuhiro;Matsuyama, Masato;Ozaka, Masato;Inoue, Dai;Muramatsu, Yusuke;Ishii, Hiroshi;Junko, Ueda;Ueno, Makoto;Egawa, Naoto;Nakao, Haruhisa;Mori, Mitsuru;Matsuo, Keitaro;Nishiyama, Takeshi;Ohkawa, Shinichi;Hosono, Satoyo;Wakai, Kenji;Nakamura, Kozue;Tamakoshi, Akiko;Kuruma, Sawako;Nojima, Masanori;Takahashi, Mami;Shimada, Kazuaki;Yagyu, Kiyoko;Kikuchi, Shogo;Lin, Yingsong 391
Background: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. Materials and Methods: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. Results: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed. Conclusions: Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study. -
Obesity has been considered as an important risk factor for the development of colorectal cancer (CRC), but the association has not been fully elucidated. Obesity is linked significantly to adipose tissue dysfunction and to alteration of adipokines in blood; in particular, obesity-induced inflammation is thought to be an important link between obesity and colorectal cancer. Based on epidemiological studies, we undertook a systematic review to understand the association of circulating levels of selected adipokines, including adiponectin, leptin, resistin, IL-6 and TNF-
${\alpha}$ , with the level of CRC risk. Most prospective studies suggested protective effects of adiponectin, but these were attenuated by body mass index (BMI) and waist circumference (WC) data in our meta-analysis. On the other hand, meta-analyses for leptin and CRC did not demonstrate any association, similar to the results of systematic review. Although it proved difficult to determine whether other selected adipokines (resistin, IL-6 and TNF-${\alpha}$ ) were related to CRC risk due to small number of reports, the present systematic review suggested a positive association with elevated resistin levels but null associations with IL-6 and TNF-${\alpha}$ . -
Wei, Guo;Nie, Ming-Ming;Shen, Xiao-Jun;Xue, Xu-Chao;Ma, Li-Ye;Du, Cheng-Hui;Wang, Shi-Liang;Bi, Jian-Wei 407
Objective: To observe local and systemic toxicity after sustained-release 5-fluorouracil (5-Fu) implantation in canine peritoneum and para-aortic abdominalis and the changes of drug concentration in the local implanted tissue with time. Methods: 300 mg sustained-release 5-Fu was implanted into canine peritoneum and para-aorta abdominalis. Samples were taken 3, 5, 7 and 10 days after implantation for assessment of changes and systemic reactions. High performance liquid chromatography was applied to detect the drug concentrations of peritoneal tissue at different distances from the implanted site, lymphatic tissue of para-aortic abdominalis, peripheral blood and portal venous blood. Results: 10 days after implantation, the drug concentrations in the peritoneum, lymphatic tissue and portal vein remained relatively high within 5 cm of the implanted site. There appeared inflammatory reaction in the local implanted tissue, but no visible pathological changes such as cell degeneration and necrosis, and systemic reaction like anorexia, nausea, vomiting and fever. Conclusions: Sustained-release 5-Fu implantation in canine peritoneum and para-aortic abdominalis can maintain a relatively high tumour-inhibiting concentration for a longer time in the local implanted area and portal vein, and has mild local and systemic reactions. Besides, it is safe and effective to prevent or treat recurrence of gastrointestinal tumours and liver metastasis. -
Tiwari, Ram Vinod;Megalamanegowdru, Jayachandra;Parakh, Abhinav;Gupta, Anjali;Gowdruviswanathan, Shailarani;Nagarajshetty, Praveen Malavalli 413
Background: Prisoners represent a population group that is disadvantaged, socially deprived and underprivileged, needing particular attention with regard to provision of necessary oral health care, health promotion and motivation and tobacco cessation. Considering the situation in prisons, smoking and tobacco chewing are burning issues related to health deterioration and economic loss that seem to be overlooked by the public health sectors. Aim: To assess prisoners' perception of tobacco use and cessation in Chhatisgarh, India. Materials and Methods: A pre-tested, close ended questionnaire was administered in the form of extensive face to face interviews, to assess perceptions regarding tobacco use and cessation in the central jail of Durg District of Chhattisgarh state, India. Results: Prevalence of tobacco usage amongst the prisoners was found to be 61%. Some 27% reported smoking, 44% used tobacco in the chewable form and 29% indulged in consuming tobacco in both forms i.e. smoked as well as chewed. Results suggest several recommendations for policy relevance such as provision of a prison dentist, a tobacco cessation counseling program and targeted eradication of oral cancer by educating the prisoners. Conclusions: Health is a fundamental human "right of everyone to the enjoyment of the highest attainable standard of physical and mental well-being". This applies to prisoners just as it does to every other human being. The alarming findings in the study suggest the need for dental treatment facilities and tobacco cessation counseling in prisons. -
Qadri, Sumyra Khurshid;Hamdani, Nissar Hussain;Shah, Parveen;Baba, Khalil Mohammad 419
Background: Lymphadenopathy is a common presentation in both benign and malignant diseases which need to be diagnosed without delay. Fine needle aspiration cytology (FNAC) helps us diagnose a disease and follow its course, including the response to therapy. Aim: This study aimed to analyze the clinicopathological features of metastatic lymphadenopathy and the diagnostic utility of FNAC in our setting. Materials and Methods: This two-year prospective study included all the patients with metastatic lymphadenopathy, diagnosed with FNAC. Results: A total of 412 cases (male:female ratio, 1.3:1; age range, 3 to 90 years) were studied. Supraclavicular lymph nodes were involved most commonly (50.5%). The commonest metastatic tumor was squamous cell carcinoma in general (30.1%) and in males (37.6%), and infiltrating ductal carcinoma (25.3%) in females. Lung, with 64 (15.5%) cases followed by esophagus, 60 (14.6%) cases; breast, 49 (11.9%) cases; skin, 32 (7.8%) cases; and stomach, 25 (6.1%) cases were the most common primary sites of malignancy. In 69 patients, excision biopsy was performed. Histopathological findings correlated well with that of cytology in all these cases. Conclusions: FNAC is an important tool in the diagnostic work up of metastatic lymphadenopathy, which in the hands of an experienced and skilful cytopathologist can avoid the need for excision biopsy. -
Tatiyachonwiphut, Molpen;Jaishuen, Atthapon;Sangkarat, Suthi;Laiwejpithaya, Somsak;Wongtiraporn, Weerasak;Inthasorn, Perapong;Viriyapak, Boonlert;Warnnissorn, Malee 423
Aim: To evaluate the agreement between colposcopic diagnosis and cervical pathology a retrospective chart review was performed. Materials and Methods: This study included 437 patients who underwent colposcopy and cervical biopsy or conization at Siriraj Hospital from October 2010 - December 2012. The patient clinical characteristics, cervical cytology results, colposcopic diagnoses, cervical pathology results were recorded and correlations between variables were analyzed. Results: Agreement of colposcopic diagnosis and cervical pathology was matched in 253 patients (57.9%). The strength of agreement with weighted Kappa statistic was 0.494 (p<0.001). Colposcopic diagnoses more often overestimated (31.1%) than underestimated (11%) the cervical pathology. Agreement of colposcopic diagnosis and cervical pathology within 1 grade was found in 411 patients (94.1%). Positive predictive value (PPV) of high grade colposcopy or more was 75.5%, whereas the negative predictive value (NPV) of insignificant and low grade colposcopy was 83.8%. False positives of high grade colposcopy or more were 21%. False negatives of insignificant or low grade colposcopy were 19.1%. Conclusions: Strength of agreement between colposcopic diagnosis and cervical pathology was found to be only moderate. A biopsy at colposcopy should be performed at a gold standard level to detect high grade lesions. -
Wang, Ju-Bo;Dong, Dan-Feng;Wang, Mao-De;Gao, Ke 427
Isocitrate dehydrogenase (IDH) is of great importance in cell metabolism and energy conversion. IDH mutation in glioma cells is reported to be associated with an increased overall survival. However, effects biological behavior of therapy of gliomas are unclear. Here, we investigated the influence of wild-type and mutated IDH genes on glioma cell biological behavior and response to chemotherapy. Relevant mechanisms were further explored. We designed our study on the background of the IDHR132H mutation. Stable cell lines were constructed by transfection. The CCK-8 method was used to assess cell proliferation, flow cytometry for the cell cycle and cell apoptosis, and the transwell method for cell invasion. Nude mouse models were employed to determine tumorigenesis and sensitivity to chemotherapy. Western blotting was used to detect relevant protein expression levels. We found that overexpression of wild IDH1 gene did not cause changes in the cell cycle, apoptosis and invasion ability. However, it resulted in chemotherapy resistance to a high dose of temozolomide (TMZ) in vivo and in vitro. The IDH1 mutation caused cell cycle arrest in G1 stage and a reduction of proliferation and invasion ability, while raising sensitivity to chemotherapy. This may provide an explanation for the better prognosis of IDH1 mutated glioma patients and the relative worse prognosis of their wild-type IDH1 counterparts. We also expect IDH1 mutations may be optimized as new targets to improve the prognosis of glioma patients. -
A Single Measure of Cancer Burden Combining Incidence with Mortality Rates for Worldwide ApplicationKim, Jeong Lim;Cho, Kyoung-Hee;Park, Eun-Cheol;Cho, Woo Hyun 433
We attempted to develop an indicator combining incidence with mortality rates (single measure of cancer burden, SMCB) and to compare the magnitudes of cancer burden by world region. The SMCB was used to measure the size of cancer burden summarizing the incidence and mortality. The incidence and mortality were divided in equivalent forms and were split. The criteria dividing the size of cancer burden were used as the maximum incidence and mortality by men and women according to the world database, and the value corresponding to 10% of each maximum was set as the cut-off value. In SMCB, the size of cancer burden was highest for men with lung cancer (SMCB=18) and for women with breast cancer (SMCB=14) in MDR (more developed regions) compared to the size of burden in LDR (lower developed regions) (lung, SMCB=11, breast, SMCB=8). For men, the size of cancer burden by region was highest in EURO (SMCB=18, lung), followed by WPRO (SMCB=16, lung), PAHO (SMCB=14, prostate), AFRO (SMCB=8, prostate) and SEARO (SMCB=7, lung). Moreover, for women, the size of cancer burden was greatest in EURO (SMCB=14, breast), followed by PAHO (SMCB=13, breast), AFRO (SMCB=11, cervix uteri), EMRO (SMCB=9, breast) or SEARO (SMCB=8, cervix uteri) and WPRO (SMCB=7, lung). The summary indicator will help to provide a priority setting for reducing cancer burden in health policy. -
Zare, Ali;Mahmoodi, Mahmood;Mohammad, Kazem;Zeraati, Hojjat;Hosseini, Mostafa;Naieni, Kourosh Holakouie 441
Background: Multi-state models are appropriate for cancer studies such as gastrectomy which have high mortality statistics. These models can be used to better describe the natural disease process. But reaching that goal requires making assumptions like Markov and homogeneity with time. The present study aims to investigate these hypotheses. Materials and Methods: Data from 330 patients with gastric cancer undergoing surgery at Iran Cancer Institute from 1995 to 1999 were analyzed. To assess Markov assumption and time homogeneity in modeling transition rates among states of multi-state model, Cox-Snell residuals, Akaikie information criteria and Schoenfeld residuals were used, respectively. Results: The assessment of Markov assumption based on Cox-Snell residuals and Akaikie information criterion showed that Markov assumption was not held just for transition rate of relapse (state 1${\rightarrow}$ state 2) and for other transition rates - death hazard without relapse (state 1${\rightarrow}$ state 3) and death hazard with relapse (state 2${\rightarrow}$ state 3) - this assumption could also be made. Moreover, the assessment of time homogeneity assumption based on Schoenfeld residuals revealed that this assumption - regarding the general test and each of the variables in the model- was held just for relapse (state 1${\rightarrow}$ state 2) and death hazard with a relapse (state 2${\rightarrow}$ state 3). Conclusions: Most researchers take account of assumptions such as Markov and time homogeneity in modeling transition rates. These assumptions can make the multi-state model simpler but if these assumptions are not made, they will lead to incorrect inferences and improper fitting. -
Palasap, Adisak;Limpaiboon, Temduang;Boonsiri, Patcharee;Thapphasaraphong, Suthasinee;Daduang, Sakda;Suwannalert, Prasit;Daduang, Jureerut 449
Background: Extracts of Caesalpinia mimosoides Lamk has been reported to possess anticancer effects, but the active ingredients and the anti-cancer mechanisms are still unknown. Materials and Methods: The effects of a C mimosoides Lamk extract on cell proliferation and apoptosis induction in human cervical carcinoma cell lines, namely HeLa, SiHa, and C33A, as well as in normal Vero cells, were investigated. Results: Treatment with 5 active fractions (F17-F21) of C mimosoides Lamk methanol extracts inhibited cell viability in a dose- and time-dependent manner. Neutral red assays indicated that treatment with F21 significantly decreased the viability of all cervical cancer cell lines compared to F21-treated normal cells. In addition, HPLC analysis revealed that F21 contained multiple phenolic compounds, namely gallic acid, caffeine, vanillic acid, ferulic acid and resveratrol. F21 had the lowest IC50 and, therefore, a much higher cytotoxicity than F20, F17, F19, and F18 by 20-, 25-, 46- and 47- fold, respectively. Analysis of activation of the apoptosis pathway using a caspase 3/7 activity assay revealed that F21 treatment resulted in a considerable increase in caspase activation in all cancer cell lines tested. At the same concentration of F21, HeLa cells had the highest caspase activity (6.5-fold) compared to the control. Conclusion: C mimosoides Lamk may be of value as an alternative therapeutic agent, especially in combination with other compounds offering possible of synergy of action. Moreover, HPV- and non-HPV-related cervical cancer cells may differ in their responses to treatment regimens. -
Katayama, Kayoko;Yokoyama, Kazuhito;Yako-Suketomo, Hiroko;Okamoto, Naoyuki;Tango, Toshiro;Inaba, Yutaka 455
Background: The purpose of the present study was to determine geographic clustering of breast cancer incidence in Kanagawa Prefecture, using cancer registry data. The study also aimed at examining the association between socio-economic factors and any identified cluster. Materials and Methods: Incidence data were collected for women who were first diagnosed with breast cancer during the period from January to December 2006 in Kanagawa. The data consisted of 2,326 incidence cases extracted from the total of 34,323 Kanagawa Cancer Registration data issued in 2011. To adjust for differences in age distribution, the standardized mortality ratio (SMR) and the standardized incidence ratio (SIR) of breast cancer were calculated for each of 56 municipalities (e.g., city, special ward, town, and village) in Kanagawa by an indirect method using Kanagawa female population data. Spatial scan statistics were used to detect any area of elevated risk as a cluster for breast cancer deaths and/or incidences. The Student t-test was performed to examine differences in socio-economic variables, viz, persons per household, total fertility rate, age at first marriage for women, and marriage rate, between cluster and other regions. Results: There was a statistically significant cluster of breast cancer incidence (p=0.001) composed of 11 municipalities in southeastern area of Kanagawa Prefecture, whose SIR was 35 percent higher than that of the remainder of Kanagawa Prefecture. In this cluster, average value of age at first-marriage for women was significantly higher than in the rest of Kanagawa (p=0.017). No statistically significant clusters of breast cancer deaths were detected (p=0.53). Conclusions: There was a statistically significant cluster of high breast cancer incidence in southeastern area of Kanagawa Prefecture. It was suggested that the cluster region was related to the tendency to marry later. This study methodology will be helpful in the analysis of geographical disparities in cancer deaths and incidence. -
Kumagai, Hozumi;Kusaba, Hitoshi;Okumura, Yuta;Komoda, Masato;Nakano, Michitaka;Tamura, Shingo;Uchida, Mayako;Nagata, Kenichiro;Arita, Shuji;Ariyama, Hiroshi;Takaishi, Shigeo;Akashi, Koichi;Baba, Eishi 461
Background: Antiemetic triplet therapy including dexamethasone (DEX) is widely used for patients receiving highly emetogenic chemotherapy (HEC). In Japan, the appropriate dose of DEX has not been established for this combination. Materials and Methods: To assess the efficacy and safety of increased-dose DEX, we retrospectively examined patients receiving HEC with antiemetic triplet therapy. Results: Twenty-four patients (fosaprepitant group) were given an increased-dose of DEX (average total dose: 45.8mg), fosaprepitant, and 5-HT3 antagonist. A lower-dose of DEX (33.6mg), oral aprepitant, and 5-HT3 antagonist were administered to the other 48 patients (aprepitant group). The vomiting control rates in the fosaprepitant and aprepitant groups were 100% and 85.4% in the acute phase, and were 75.0% and 64.6% in the delayed phase. The incidences of toxicity were similar comparing the two groups. Conclusions: Triplet therapy using an increased-dose of DEX is suggested to be safe and effective for patients receiving HEC. -
Guo, Jian-Rong;Xu, Feng;Jin, Xiao-Ju;Shen, Hua-Chun;Liu, Yang;Zhang, Yi-Wei;Shao, Yi 467
Objective: To observe the effects of allogeneic and autologous transfusion on cellular immunity, humoral immunity and secretion of serum inflammatory factors and perforin during the perioperative period in patients with malignant tumors. Methods: A total of 80 patients (age: 38-69 years; body weight: 40-78 kg; ASA I - II) receiving radical operation for gastro-intestinal cancer under general anesthesia were selected. All the patients were divided into four groups based on the methods of infusion and blood transfusion: blank control group (Group C), allogeneic transfusion group (group A), hemodiluted autotransfusion Group (Group H) and hemodiluted autotransfusion + allogenic transfusion Group (A+H group). Venous blood was collected when entering into the surgery room ($T_0$ ), immediately after surgery ($T_1$ ) and 24h ($T_2$ ), 3d ($T_3$ ) and 7d ($T_4$ ) after surgery, respectively. Moreover, flow cytometry was applied to assess changes of peripheral blood T cell subpopulations and NK cells. Enzyme linked immunosorbent assays were performed to determine levels of IL-2, IL-10, TNF-${\alpha}$ and perforin. Immune turbidimetry was employed to determine the changes in serum immunoglobulin. Results: Both CD3+ and NK cells showed a decrease at$T_1$ and$T_2$ in each group, among which, in group A, CD3+ decreased significantly at$T_2$ (P<0.05) compared with other groups, and CD3+ and NK cell reduced obviously only in group A at$T_3$ and$T_4$ (P<0.05). CD4+ cells and the ratio of D4+/CD8+ were decreased in groups A, C and A+H at$T_1$ and$T_2$ (P<0.05). No significant intra- and inter-group differences were observed in CD8+ of the four groups (P<0.05). IL-2 declined in group C at$T_1$ and$T_2$ (P<0.05) and showed a decrease in group A at each time point (P<0.05). Moreover, IL-2 decreased in group A + H only at$T_1$ . No significant difference was found in each group at$T_1$ (P<0.05). More significant decrease in group ?? at$T_2$ ,$T_3$ and$T_4$ compared with group A (P<0.05), and there were no significant differences among other groups (P>0.05). IL-10 increased at$T_1$ and$T_2$ in each group (P<0.05), in which it had an obvious increase in group A, and increase of IL-10 occurred only in group A at$T_3$ and$T_4$ (P<0.05). TNF-${\alpha}$ level rose at$T_1$ (P<0.05), no inter- and intra-group difference was found in perforin in all groups (P<0.05). Compared with the preoperation, both IgG and IgA level decreased at$T_1$ in each group (P<0.05), and they declined only in Group A at$T_2$ and$T_3$ (P<0.05), and these parameters were back to the preoperative levels in other groups. No significant differences were observed between preoperative and postoperative IgG and IgA levels in each group at$T_4$ (P>0.05). No obvious inter- and intra-group changes were found in IgM in the four groups (P>0.05). Conclusions: Allogeneic transfusion during the perioperative period could obviously decrease the number of T cell subpopulations and NK cells and the secretion of stimulating cytokines and increase the secretion of inhibiting cytokines in patients with malignant tumors, thus causing a Th1/Th2 imbalance and transient decreasing in the content of plasma immune globulin. Autologous transfusion has little impact and may even bring about some improvement oo postoperative immune function in patients with tumors. Therefore, cancer patients should receive active autologous transfusion during the perioperative period in place of allogeneic transfusion. -
Asmaa, Mat Jusoh Siti;Al-Jamal, Hamid Ali Nagi;Ang, Cheng Yong;Asan, Jamaruddin Mat;Seeni, Azman;Johan, Muhammad Farid 475
Background: Pereskia sacharosa is a genus of cacti widely used in folk medicine for cancer-related treatment. Anti-proliferative effects have been studied in recent years against colon, breast, cervical and lung cancer cell lines, with promising results. We here extended study of anti-proliferative effects to a blood malignancy, leukemia. Materials and Methods: Two leukemic cell lines, MV4-11 (acute myeloid leukemia) and K562 (chronic myeloid leukemia), were studied.$IC_{50}$ concentrations were determined and apoptosis and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell-cycle related regulatory proteins was assessed by Western blotting. Results: P sacharosa inhibited growth of MV4-11 and K562 cells in a dose-dependent manner. The mode of cell death was via induction of intrinsic apoptotic pathways and cell cycle arrest. There was profound up-regulation of cytochrome c, caspases, p21 and p53 expression and repression of Akt and Bcl-2 expression in treated cells. Conclusions: These results suggest that P sacharosa induces leukemic cell death via apoptosis induction and changes in cell cycle checkpoint, thus deserves further study for anti-leukemic potential. -
Cheung, Min Rex;Kang, Josephine;Ouyang, Daniel;Yeung, Vincent 483
Aim: This study employed public use National Health and Nutrition Examination Survey (NHANES III) data to investigate the association between urinary cadmium (UDPSI) and all cause, all cancer and prostate cancer mortalities in men. Patients and Methods: NHANES III household adult, laboratory and mortality data were merged. The sampling weight used was WTPFEX6, with SDPPSU6 applied for the probability sampling unit and SDPSTRA6 to designate the strata for the survey analysis. Results: For prostate cancer death, the significant univariates were UDPSI, age, weight, and drinking. Under multivariate logistic regression, the significant covariates were age and weight. For all cause mortality in men, the significant covariates were UDPSI, age, and poverty income ratio. For all cancer mortality in men, the significant covariates were UDPSI, age, black and Mexican race. Conclusions: UDPSI was a predictor of all cause and all cancer mortalities in men as well as prostate cancer mortality. -
Wu, Lu;Liu, Yan-Yang;Li, Zhi-Xi;Zhao, Qian;Wang, Xia;Yu, Yang;Wang, Yu-Yi;Wang, Yi-Qin;Luo, Feng 489
Background: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. Methods: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method. Results: Penfluridol inhibited the proliferation of B16 melanoma (B16/F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. Conclusion: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms. -
Wen, Chun-Jie;Wu, Lan-Xiang;Fu, Li-Juan;Shen, Dong-Ya;Zhang, Xue;Zhang, Yi-Wen;Yu, Jing;Zhou, Hong-Hao 495
Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism.$17{\beta}$ -estradiol ($E_2$ ), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH$E_2$ ) and 4-hydroxyestradiol ($4-OH\;E_2$ ) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that$2-OH\;E_2$ has putative protective effects, while$4-OH\;E_2$ is genotoxic and has potent carcinogenic activity. Thus, the ratio of$2-OH\;E_2/4-OH\;E_2$ is a critical determinant of the toxicity of$E_2$ in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect$E_2$ metabolism in a more protective pathway in breast cancer MCF-7 cells.