Asian Pacific Journal of Cancer Prevention
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
- 월간
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
과학기술표준분류
- 보건의료 > 의약품/의약품개발
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.
KSCI제15권5호
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Moore, Malcolm A.;Sangrajrang, Suleeporn;Bray, Freddie 1891
In February 6-7th, the Thai National Cancer Institute, the International Agency for Research on Cancer and its Mumbai Hub for Cancer Registration, together with the International Association of Cancer Registries and the APOCP/APJCP, jointly organized an Asian cancer registry forum to discuss regional cooperation for cancer registration. Held in the Grande Mercure Fortune Hotel, Bangkok, the meeting brought together leading scientists in cancer registration from South-East and North-East Asia as well as Australia, India and Iran and IARC itself, with coverage of various priorities and challenges of cancer registries regarding cancer control policy, operational parameters, assessment of survival and contributions to screening, for example. The current situation was highlighted and future directions and possible expansion of activities were discussed, with especial attention to the necessity for networks to help improve cancer registration across Asia and Africa. -
Cancer registries have fundamental roles in cancer surveillance, research, and health services planning, monitoring and evaluation. Many are now assuming a broader role by contributing data for health-service management, alongside data inputs from other registries and administrative data sets. These data are being integrated into de-identified databases using privacy-protecting data linkage practices. Structured pathology reporting is increasing registry access to staging and other prognostic descriptors. Registry directions need to vary, depending on local need, barriers and opportunities. Flexibility and adaptability will be essential to optimize registry contributions to cancer control.
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Garg, Manish;Dalela, Divakar;Goel, Apul;Kumar, Manoj;Sankhwar, Satya Narayan 1897
Cancer prostate is the most common solid malignancy in males of developed countries. With increasing knowledge of the aetiology, pathogenesis and natural history of the disease, influences of dietary factors on prostate cancer development have become more evident. There is ample evidence in the literature of significance of dietary constituents for prostate cancer including vitamins A, D and E. Different vitamins have been found to effect the growth and proliferation of prostate cancer cells as evident in epidemiological, experimental and clinical studies. Various factors play the major role in determining the relationship between these vitamins and prostate cancer in terms of environmental, pharmacological, or genetic aspects. To explore these aspects, the present article reviews the literature on the present status of vitamin use for prevention and management of prostate cancer. -
Silva, Marcela Fernandes;Khokhar, Abdur Rehman;Qureshi, Muhammad Zahid;Farooqi, Ammad Ahmad 1905
Increasingly it is being realized that despite considerable advancements in therapeutic interventions related to treatment of cancer, satisfactory results are still difficult to achieve. Rapidly accumulating evidence has started to shed light on the fact that cancer cells escape from death via constitutive activation of pro-survival signaling cascades. Cell biology and genetics have extensively enhanced our current understanding of the molecular mechanisms that underlie loss of apoptosis in cancer cells. This review is focused on ionizing radiation mediated restoration of TRAIL mediated apoptosis as evidenced by cell culture and animal model studies. Moreover, we also bring to the limelight radiation induced expression of miRNAs and how miRNAs further control response of cancer cells to radiation. -
Farooqi, Ammad Ahmad;Qureshi, Muhammad Zahid;Coskunpinar, Ender;Naqvi, Syed Kamran-Ul-Hassan;Yaylim, Ilhan;Ismail, Muhammad 1909
It is becoming progressively more understandable that between transcription and translation there lies another versatile regulator that quantitatively controls the expression of mRNAs. Identification of miRNAs as key regulators of wide ranging signaling cascades and modulators of different cell-type and context dependent activities attracted basic and clinical scientists to study modes and mechanisms in details. In line with this approach overwhelmingly increasing in vivo and in vitro studies are deepening our understanding regarding miR-421, mir-155 and miR-650 mediated regulation of cellular activities. We also attempt to provide an overview of long non coding RNAs. -
Quadri, Mir Faeq Ali;Saleh, Sanaa Mahmoud;Alsanosy, Rashad;Abdelwahab, Siddig Ibrahim;Tobaigy, Faisal Mohamed;Maryoud, Mohamed;Al-Hebshi, Nezar 1913
Background: The study is the first of its kind to be conducted in Saudi Arabia (KSA), aiming to analyze the effectiveness of an intervention program in improving the knowledge of oral cancer among the youth. Materials and Methods: A total of 1,051 young Saudis (57% males and 43% females with a mean age of$20.4{\pm}1.98$ ) were selected using multi-stage cluster sampling. Knowledge assessment was accomplished using a closed-ended questionnaire which was subjected to reliability tests. Prevalence of risk factors in relation to gender was analyzed using the chi-squared test. Effectiveness was calculated by comparing the pre- and post-intervention means, using the two-tailed paired t-test. Multiple logistic regression was employed in order to determine factors associated with awareness of risk habits, signs/symptoms and prevention of oral cancer. The significance level in this study was set at 0.05. Results: Females were seen to be more into the habit of sheesha smoking (3.3% rather than the use of other forms of risk factors. Prevalence of diverse risk factors such as cigarette smoking (20%), sheesha (15.3%), khat (27%) and shamma (9%) was seen among males. Gender and the use of modifiable risk factors among the study sample were significantly (p<0.001) associated with effectiveness of the intervention. The intervention program was highly effective (p<0.001) in improving the knowledge of oral cancer among the youth in Jazan, KSA. Multivariate analysis revealed that age and gender are the most significant factors affecting knowledge. Conclusions: The study gives a direction for further public health initiatives in this oral cancer prone region. -
Sreedevi, Aswathy;Quereshi, Mariya Amin;Kurian, Beteena;Kamalamma, Leelamoni 1919
Background: In India, breast cancer is the leading malignancy among women in a majority of the cancer registries. Therefore it is important to understand screening practices and its predictors, including in rural areas with high female literacy and good health indices. Materials and Methods: A cross-sectional study with multistage sampling was conducted in Vypin Block, Ernakulam district, Kerala, India. Four Panchayats (self administration units) were randomly chosen and a woman in every second household was invited to participate from the tenth ward of each. Thus a total of 809 women were interviewed. Results: The majority of the repondents (82.1%) were not aware of risk factors and about a third (37.9%) were not aware of symptoms of breast cancer. About half of the population studied (46.6%) had undergone screening. Age (35-50 years), being married, health professionals as source of information and working were significant predictors of screening. Logistic regression showed that older women (35-50 yrs) were more likely to practice screening. Out of the never screened, about a third (35%) were desirous of doing it, but had not for various reasons and 53.5% were not willing to screen. The reasons identified for not screening among those desirous of doing it were grouped into knowledge 66 (43.4%), resources 23 (15.1%) and psychosocial 32(21.1%) factors. Unmarried women were significantly more likely to express factors related to all the three domains. Conclusions: This study showed that in spite of the absence of a population-based screening program, about half of the study population had undergone some type of screening. The older women (35-50 years) in particular were significantly more likely to practice screening. At this critical juncture, a high quality breast cancer awareness and screening initiative can help to consolidate the gains and tackle knowledge, resource and psychosocial barriers. -
Liu, Yong-Chao;Zhao, Jing;Hu, Cheng-En;Gan, Jun;Zhang, Wen-Hong;Huang, Guang-Jian 1925
Background: Vascular endothelial growth factor-C (VEGF-C), which contributes to lymphatic metastasis (LM) in malignant disease, is one of the most important factors involved in physical and pathological lymphangiogenesis. Some VEGF-C related factors such as sine oculis homeobox homolog (SIX) 1, contactin (CNTN) 1 and dual specificity phosphatase (DUSP) 6 have been extensively studied in malignancies, but their expression levels and associations have still to be elucidated in stomach cancer. Methods: We detected their expression levels in 30 paired stomach cancer tissues using quantitative real-time reverse transcription-PCR (qRT-PCR). The expression and clinical significance of each factor was analyzed using Wilcoxon signed rank sum test. The correlation among all the factors was performed by Spearman rank correlation analysis. Results: The results suggest that VEGF-C and CNTN1 are significantly correlated with tumor size, SIX1 with the age and CNTN1 also with the cTNM stage. There are significant correlations of expression levels among VEGF-C, SIX1, CNTN1 and DUSP6. Conclusions: There exists an important regulatory crosstalk involving SIX1, VEGF-C, CNTN1 and DUSP6 in stomach cancer. -
Aquea, Gisela;Bresky, Gustavo;Lancellotti, Domingo;Madariaga, Juan Andres;Zaffiri, Vittorio;Urzua, Ulises;Haberle, Sergio;Bernal, Giuliano 1931
Background: Gastric cancer (GC) ranks as one of the major causes of mortality due to cancer worldwide. In Chile, it is currently the leading cause of cancer death. Identification of novel molecular markers that may help to improve disease diagnosis at early stages is imperative. Materials and Methods: Using whole-genome DNA microarrays we determined differential mRNA levels in fresh human GC samples compared to adjacent healthy mucosa from the same patients. Genes significantly overexpressed in GC were validated by RT-PCR in a group of 14 GC cases. Results: The genes CD248, NSD1, RAB17, ABCG8, Ephb1 and P2RY2 were detected as the top overexpressed in GC biopsies. P2RY2, Ephb1 and CD248 showed the best sensitivity for GC detection with values of 92.9%, 85.7% and 64.3% (p<0.05), respectively. Specificity was 85.7%, 71.4% and 71.4% (p<0.05), for each respectively. -
Verma, Shiv Prakash;Tripathi, Vikash Chandra;Das, Parimal 1937
Aims: To evaluate anti-cancer activity of Asparagus racemosus (AR) leaf extract on UOK146, a renal cell carcinoma cell line, and explore its mechanism of action. Materials and Methods: Dried AR leaves were extracted with chloroform and dissolved in DMSO. This extract was applied to UOK146 and cell death was estimated by MTT assay. In addition PRCC-TFE3 fusion transcripts were detected by real time PCR. Results: Extract was found to be cytotoxic with an$IC_{50}$ of 0.9 mg/ml as estimated by dose response curve. Antitumor activity of the permissible doses of the extract was assessed by the down regulation of PRCC-TFE3 fusion transcript (38%) responsible for oncogenicity of the UOK146 cell line. No increment in the BAX, a proapoptotic marker level was observed. Conclusions: Evidence of antiproliferative effect, PRCC-TFE3 fusion transcript inhibition and static BAX level clearly indicate that AR extract provides or elicits an apoptosis independent anticancer effect on RCC cells by some specific mechanism of regulation. -
Jiang, Nan;Zhao, Jin-Zhi;Chen, Xiao-Cen;Li, Li-Ya;Zhang, Li-Juan;Zhao, Yue 1943
Purpose: The prevalence of weight loss in esophageal carcinoma patients is high and associated with impairment of physical function, increased psychological distress and low quality of life. It is not known which factors may contribute to weight loss in patients with esophageal carcinoma during radiotherapy in China. The objective of this study was to identify the associated demographic and clinical factors influencing weight loss. Methods: We evaluated 159 esophageal carcinoma patients between August 2010 and August 2013 in a crosssectional, descriptive study. Patient characteristics, tumor and treatment details, psychological status, adverse effects, and dietary intake were evaluated at baseline and during radiotherapy. A multivariate logistic regression analyss was performed to identify the potential factors leading to weight loss. Results: 64 (40.3%) patients had weight loss${\geq}5%$ during radiotherapy. According to logistic regression analysis, depression, esophagitis, and loss of appetite were adverse factors linked to weight loss. Dietary counseling, early stage disease and total energy intake${\geq}1441.3$ (kcal/d) were protective factors. Conclusions It was found that dietary counseling, TNM stage, total energy intake, depression, esophagitis, and loss of appetite were the most important factors for weight loss. The results underline the importance of maintaining energy intake and providing dietary advice in EC patients during RT. At the same time, by identifying associated factors, medical staff can provide appropriate medical care to reduce weight loss. Further studies should determine the effect of these factors on weight loss and propose a predictive model. -
Winarto, Hariyono;Laihad, Bismarck Joel;Nuranna, Laila 1949
Background: CA125 and HE4 are used in calculating Risk of Malignancy Algorithm (ROMA); and Risk of Malignancy Index (RMI). However, studies showed that normal levels of CA125, and HE4 differ among ethnicities such as between Asians and Caucasians, thus affecting the accuracy of the RMI score and ROMA in predicting ovarian malignancy. This study aimed to determine whether new or modified cutoff values for Ca125, HE4, the RMI score, and ROMA resulted in a better prediction of malignancy compared with the previous or standard ones. Materials and Methods: Serum level of CA125 and HE4 from 128 patients with diagnosis of ovarian tumor that had been collected before surgery at Cipto Mangunkusumo General Hospital (CMH) in Jakarta from November 2010 until May 2011 were reviewed and analysed. The standard cutoff values of these biomarkers, RMI, and ROMA were modified by using logistic regression model. The modified cutoff values were compared to the standard cutoff values in terms of sensitivity, specificity, and accuracy. Results: The modified cutoff value of CA125, HE4, RMI score and ROMA were 165.2 U/mL, 103.4 pM, 368.7, 28/54. The sensitivity and specificity of the modified cutoff values CA125, HE 4, RMI score and ROMA in differentiating benign from malignant and borderline were 67% and 75,4%; 73.1% and 85.2%; 73.1% and 80.3%; and 77.6% and 86.9%. While the sensitivity and specificity of the standard cutoff value of CA125; HE4; RMI score; and ROMA were 91% and 24.6%; 83.6% and 65%; 80.6% and 65.6%; and 91.0% and 42.6%. The accuracy of modified cutoff values compared with standard cutoff values were: 71.2% vs 59.3%, 78.9% vs 75% vs, 76.5% vs 73.4%, and 82% vs 67.9%. Conclusions: The new or modified cutoff values of Ca125, HE4, RMI score and ROMA resulted in higher accuracy compared to the previous or standard ones, at the cost of reduced sensitivity. -
Kostak, Melahat Akgun;Mutlu, Aysel;Bilsel, Aysegul 1955
Background: This study was performed to determine the experiences of nursing students in caring for paediatric cancer patients and their families. Materials and Methods: This qualitative survey was carried out with 14 students studying in the nursing department of the Faculty of Health Sciences of a university in Edirne, Turkey. Data were obtained through focus group interviews and evaluated based on a qualitative content analysis. Results: It was determined that students, for the most part, experienced problems related to communication, sadness, helplessness, fear, anxiety, resentment and anger. In addition, the students were affected most often by effects of the disease and invasive procedures on paediatric cancer patients and their families during the process of caring for them in the oncology clinic. Conclusions: It would be useful to inform nursing students, prior to clinical practice, about the special needs of paediatric cancer patients and families who stay in oncology clinics, and to follow up with appropriate guidance during the clinical practices. -
Fan, Fang-Tian;Shen, Cun-Si;Tao, Li;Tian, Chao;Liu, Zhao-Guo;Zhu, Zhi-Jie;Liu, Yu-Ping;Pei, Chang-Song;Wu, Hong-Yan;Zhang, Lei;Wang, Ai-Yun;Zheng, Shi-Zhong;Huang, Shi-Le;Lu, Yin 1961
Pyruvate kinase isozyme type M2 (PKM2) was first found in hepatocellular carcinoma (HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by the ERK pathway, regulated${\beta}$ -catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases. -
Sutandyo, Noorwati;Ramli, Ramadhan;Sari, Lenny;Soeis, Dewi Syafriyetti 1971
Background: Tongue cancer is still a major health problem in most developing countries around the world. Statistics shown the number of tongue cancers, especially in early age, to be increasing, with poor survival. Objective: To analyze the characteristic profile of tongue cancer patients in Indonesia as well as the survival rate. Materials and Methods: A cross sectional study was conducted in Dharmais National Cancer Hospital by collecting general, clinical, and survival data of tongue cancer patients from medical records for January 2009 to April 2012. Results: Tongue cancer incidence increased year by year. The average age of tongue cancer patients was 47.5 years, and males predominated, accounting for 64.5% of cases. Most patients presented at an advanced stage (69.6%). The histopathology type was squamous cell carcinoma in the vast majoriy (96.8%). The therapies applied were surgery (45.6%), radiation (63.6%) and chemotherapy (57.6%). The survival rate after one year is 60.6% and after two years was 12.1%. In addition, median survival of tongue cancer patients was 20 months (95% confidence interval 9.07-30.9). The significant factor affecting survival was size of tumor with a hazard ratio of 3.18 (95% CI, 1.02-9.93; p 0.046) for largest versus smallest categories. Conclusions: In each year, the number of tongue cancer incidents in Indonesia is increasing. The age of tongue cancer patients in Indonesia is younger compared to other countries. Moreover, the survival rates are not high. -
Alvur, Muge Tuncay;Cinar, Nursan;Akduran, Funda;Dede, Cemile 1977
Background: The popularity of the narghile waterpipe, also referred to as hookah, shisha or hubble-bubble has increased tremendously during the past few decades. The aim of this study was to expose perception of narghile among a representative sample of university students in Sakarya University campus. Materials and Methods: Written approval was taken from the local education authority. An anonymous questionnaire which was prepared by the investigators and contained 17 questions was administered. Nine of the questions were related to socio-demographic characteristics and eight were related to the students harm perceptions about waterpipe. A total of 1,320 questionnaries were received and after preliminary evaluation 1,255 (95.7%) were found to be suitable for evaluation. The data was evaluated in SPSS program by using percentages and averages. Results: The$mean{\pm}SD$ age of the students was$20.8{\pm}2.29$ years (min 18, max 32). There were 864 (68.8%) females and 391 (31.2%) males. A total of 6.3 % of the students (n=79) believed that waterpipe is not harmful because its smoke does not burn the lungs. Almost one-third (n=318) think that the carcinogenic chemicals are filtered while waterpipe smoke passes from the water; 12.1 % of the students (n=152) checked "true" for the statement of "waterpipe smoke contains no nicotine". It is seen that 14.0 % of the students (n=176) think waterpipe with fruit/aroma is healthier than plain waterpipe. Conclusions: As a result of this study, it is found out that a substantial number of university students have false beliefs on harmful effects of waterpipe smoking. -
Feng, Xiao-Shan;Yang, Yan-Tong;Gao, She-Gan;Ru, Yi;Wang, Gong-Ping;Zhou, Bo;Wang, Yu-Feng;Zhang, Peng-Fei;Li, Pu-Yu;Liu, Yong-Xuan 1981
Objective: To establish the prevalence and distribution profile of esophageal squamous cell carcinomas (ESCCs) over a 22-yr period in North China. Methods: Using endoscopy for primary diagnosis and histological analysis for the further confirmation, a total of 74,854 ESCC patients aged 20-89 between January 1985 and December 2006 were investigated to analyze the epidemiological profile including prevalence rates, distribution of age-of-onset, gender and geographical area of ESCC in Luoyang, the highest incidence area of North China. Results: A total of 4092 cases of ESCC were finally diagnosed among 74,854 patients who had their first endoscopies. The prevalence among males was higher than that among females (p<0.01), resulting in an overall male:female OR of 1.2 (95%CI, 1.2-1.3). The prevalence in rural areas was higher than in urban areas (p<0.01), resulting in an overall rural:urban OR of 2.6 (95%CI, 2.4-2.9). The rural:urban ORs and the 95% CI increased continuously from 2.6, 2.3-3.0 to 2.7, 2.2-3.3, respectively, for 4 consecutive periods during the 22-yr study period. Moreover, the median age of onset among females was higher than that among males (p<0.01). For both sexes and in both areas, the prevalence rates declined and the median age of onset rose for 4 consecutive periods in the 22-yrs time frame (p<0.01). Conculsions: These data reveal the epidemiological profile of ESCC in the area of North China, and suggest that urban areas and rural people account for a growing proportion of the ESCC patients although the prevalence of ESCC significantly declined and the median age-of-onset postponed over the 22-yrs period. Moreover, the prevalence status of ESCC in rural areas also underlines the need for public health initiatives aimed at reducing risk factors of this fatal disease. -
Gogia, Ajay;Raina, Vinod;Deo, Suryanarayan Vishnu;Shukla, Nootan Kumar;Mohanti, Bidhu Kalyan;Sharma, Daya Nand 1989
Background: The aim of this study was to assess the response rates (clinical and pathological ) with docetaxel and epirubicin combination chemotherapy and its effect on outcome. Materials and Methods: We retrospectively analysed locally advanced breast cancer (LABC) patients who received NACT from January 2008 to December 2012 in our tertiary care centre. LABC constituted 37% of all breast cancer cases and 120 patients fulfilled the eligibility criteria. The regimens used for NACT were, six cycles of DEC (docetaxel$75mg/m^2$ , epirubicin$75mg/m^2$ , cyclophosphamide$50mg/m^2$ on Day 1, 3 weekly) and a sequential regimen (4 cycles of FEC, 5-flurouracil$600mg/m^2$ , epirubicin$75mg/m^2$ , cyclophosphamide$600mg/m^2$ followed by 4 cycles of docetaxel$85mg/m^2$ ). Results: The median age was 47 years (range 23-72). Ninety six ( 80 %) had T4 disease and 90% had clinically palpable lymph nodes at diagnosis. The median size of primary tumor at presentation was 5.9 cm. Hormone receptor positivity was seen in 55% and HER2/neu positivity, in 25%. Triple negative breast cancers constituted 25 % of the cases. The overall clinical response rate (complete or partial ) was 85% and pathological complete responses were obtained in 15%. Four cases defaulted, 5 patients died of treatment related toxicity and 15% developed febrile neutropenia on DEC. The median duration of follow up was 22 months. The median time to relapse was 20 months and the 3 year relapse free and overall survival rates were 50% and 70% respectively. Conclusions: LABC constituted 37% of all breast cancer cases at our institute. With NACT, pCR was seen in 15% of the cases. Sequential chemotherapy was better tolerated than concurrent anthracyline and taxane chemotherapy with a similar pCR. -
Saikia, Bhaskar Jyoti;Phukan, Rup Kumar;Sharma, Santanu Kumar;Sekhon, Gaganpreet Singh;Mahanta, Jagadish 1993
Background: This study aimed to explore the role of XRCC1 (Arg399Gln) and XPD (Lys751Gln) gene polymorphisms, lifestyle and environmental factors as well as their possible interactions in propensity to develop lung cancer in a population with high incidence from North East India. Materials and Methods: A total of 272 lung cancer cases and 544 controls were collected and XRCC1 (Arg399Gln) and XPD (Lys751Gln) genotypes were analyzed using a polymerase chain reaction based restriction fragment length polymorphism assay. Conditional multiple logistic regression analysis was used to calculate adjusted odds ratios and 95% confidence intervals after adjusting for confounding factors. Results: The combined Gln/Gln genotype of XRCC1 and XPD genes (OR=2.78, CI=1.05-7.38; p=0.040) was significantly associated with increased risk for lung cancer. Interaction of XRCC1Gln/Gln genotype with exposure of wood combustion (OR=2.56, CI=1.16-5.66; p=0.020), exposure of cooking oil fumes (OR=3.45, CI=1.39-8.58; p=0.008) and tobacco smoking (OR=2.54, CI=1.21-5.32; p=0.014) and interaction of XPD with betel quid chewing (OR=2.31, CI=1.23-4.32; p=0.009) and tobacco smoking (OR=2.13, CI=1.12-4.05; p=0.022) were found to be significantly associated with increased risk for lung cancer. Conclusions: Gln/Gln alleles of both XRCC1 and XPD genes appear to amplify the effects of household exposure, smoking and betel quid chewing on lung cancer risk in the study population. -
Cai, Yong-Lin;Li, Jun;Lu, Ai-Ying;Zheng, Yu-Ming;Zhong, Wei-Ming;Wang, Wei;Gao, Jian-Quan;Zeng, Hong;Cheng, Ji-Ru;Tang, Min-Zhong 2001
The objective of this study was to investigate the diagnostic significance of EBV antibody combined detection for nasopharyngeal carcinoma (NPC) in a high incidence region of southern China. Two hundred and eleven untreated NPC patients, 203 non-NPC ENT patients, and 210 healthy controls were recruited for the study. The titers of VCA/IgA and EA/IgA were assessed by immunoenzyme assay, and the levels of Rta/IgG and EBNA1/IgA were determined by enzyme-linked immunosorbent assay. The levels of VCA/IgA, EA/IgA, Rta/IgG and EBNA1/IgA demonstrated no association with gender or age (p>0.05). The receiver operating characteristic curve and the area under the curve were used to evaluate the diagnostic value. The sensitivity of VCA/IgA (98.1%) and the specificity of EA/IgA (98.5%) were the highest. When a logistic regression model was used to combine the results from multiple antibodies to increase the accuracy, the combination of VCA/IgA+Rta/IgG, whose area under the curve was 0.99, had the highest diagnostic efficiency, and its sensitivity, specificity and Youden index were 94.8%, 98.0% and 0.93 respectively. The data suggest that the combination of VCA/IgA+Rta/IgG may be most suitable for NPC serodiagnosis. -
Background: Human papilloma virus (HPV) is a common sexually transmitted infectious agent. It is estimated that 10% of all women worldwide are infected with HPV, that is some 660 million each year. HPV vaccination has a reported efficacy of more than 98% for protection against infection in females. In 2008 the Abu Dhabi Health Authority in the United Arab Emirates (UAE) introduced free HPV vaccination for all eligible schoolgirls in both public and private schools. Methods: A cross-sectional study of 640 women aged 18-50 years in the Emirate of Abu Dhabi in UAE from April 2012 to October 2012 was conducted. Results: Thirty-seven percent of the women in our sample had heard about HPV vaccination, and 80% of these would consider getting vaccinated themselves, and 87% would recommend vaccination to relatives or friends. Most women in the study (69%) had a favorable opinion about the vaccine. Only 17% of the women felt it might not be culturally acceptable, and 1% felt that there might be religious objections to HPV vaccination. Vaccine safety and recommendation by a doctor (36% each) were the factors identified most frequently by our sample of women which would enhance the uptake of the HPV vaccination. Conclusions: Knowledge about HPV vaccination among women in our sample was below average (37%); however, 80% of those who had heard about HPV vaccination were willing to be vaccinated themselves, and 87% would recommend vaccination to relatives and friends.
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Keymoosi, Hossein;Gheytanchi, Elmira;Asgari, Mojgan;Shariftabrizi, Ahmad;Madjd, Zahra 2013
Background: The aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is one of the promising markers for identifying cancer stem cells in many cancer types, along with other markers including CD44. The aim of the present study was to evaluate the expression and clinical significance of putative cancer stem cell markers, CD44 and ALDH1A1, in a series of urothelial carcinomas of urinary bladder (UCUB) by tissue microarray (TMA). Materials and Methods: A total of 159 Urothelial Carcinomas (UC) including 96 (60%) low grade and 63 (40%) high grade carcinomas were immunohistochemically examined for the expression of CD44 and ALDH1A1. Correlations of the relative expression of these markers with clinicopathological parameters were also assessed. Results: High level expression of ALDH1A1 was found in 16% (25/159) of bladder UC which was significantly correlated with increased tumor size (p value=0.002), high grade (p value<0.001), pathologic stage (T1, p value=0.007 and T2, p value<0.001) and increased rate of recurrence (p value=0.013). A high level of CD44 expression was found in 43% (68/159) of cases, being positively correlated with histologic grade (p value=0.032) and recurrence (p value=0.039). Conclusions: Taken together, our results showed that ALDH1 was concurrently expressed in a fraction of CD44+ tumors and its expression correlated with poor prognosis in UCs. ALDH1A1 could be an ideal marker for targeted therapy of UCs in combination with conventional therapies, particularly in patients with high grade carcinomas. These findings indicate that cells expressing ALDH1A1 along with CD44 can be a potential therapeutic target in bladder carcinomas. -
Yang, Yu-Feng;Zhang, Xi-Ying;Yang, Mei;He, Ze-Hua;Peng, Ning-Fu;Xie, Shu-Rui;Xie, Yan-Fang 2021
Aim: Recent research suggests that nucleophosmin (NPM) may be a prognostic marker in colorectal carcinomas (CRC). We here tested its use to predict the survival of CRC patients. Methods: We investigated NPM expression by immunohistochemistry in histologically normal to malignant colorectal tissues and evaluated its association with clinicopathological variables. Overall and disease-free survival after tumor removal were calculated by the Kaplan-Meier method, and differences in survival curves were analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis of prognostic factors. Results: NPM expression was found significantly upregulated in CRC compared to adjacent colorectal tissue, villous adenoma, tubular adenoma and normal colorectal mucosa (p<0.05 for all). NPM expression was statistically linked to cancer embolus, lymph node metastasis, differentiation grade, and recurrence of CRC. Overall and disease-free survival of NPM-negative CRC patients tended to be better than those for patients with NPM-positive lesions (log-rank statistic, p<0.05 for all). Multivariate analysis indicated NPM expression as an independent prognostic indicator for CRC patients (p<0.05 ). Conclusion: Our results suggest that NPM expression can predict the survival of CRC patients. Prognosis of CRC is determined by not only many known prognostic factors but also by NPM expression. -
Masbi, Mohammad Hosein;Mohammadiasl, Javad;Galehdari, Hamid;Ahmadzadeh, Ahmad;Tabatabaiefar, Mohammad Amin;Golchin, Neda;Haghpanah, Vahid;Rahim, Fakher 2027
Background: We aimed to assess RET proto-oncogene polymorphisms in three different Iranian families with medullary thyroid cancer (MTC), and performed molecular dynamics simulations and free energy stability analysis of these mutations. Materials and Methods: This study consisted of 48 patients and their first-degree relatives with MTC confirmed by pathologic diagnosis and surgery. We performed molecular dynamics simulations and free energy stability analysis of mutations, and docking evaluation of known RET proto-oncogene inhibitors, including ZD-6474 and ponatinib, with wild-type and mutant forms. Results: The first family consisted of 27 people from four generations, in which nine had the C.G2901A (P.C634Y) mutation; the second family consisted of six people, of whom three had the C.G2901T (P.C634F) mutation, and the third family, who included 12 individuals from three generations, three having the C.G2251A (P.G691S) mutation. The automated 3D structure of RET protein was predicted using I-TASSER, and validated by various protein model verification programs that showed more than 96.3% of the residues in favored and allowed regions. The predicted instability indices of the mutated structures were greater than 40, which reveals that mutated RET protein is less thermo-stable compared to the wild-type form (35.4). Conclusions: Simultaneous study of the cancer mutations using both in silico and medical genetic procedures, as well as onco-protein inhibitor binding considering mutation-induced drug resistance, may help in better overcoming chemotherapy resistance and designing innovative drugs. -
Minhas, Sachin;Bhalla, Sunita;Shokeen, Yogender;Jauhri, Mayank;Saxena, Renu;Verma, Ishwar Chandra;Aggarwal, Shyam 2035
Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an important protein involved in the regulation of the immune system. The +49 G/A polymorphism is the only genetic variation in the CTLA-4 gene that causes an amino acid change in the resulting protein. It is therefore the most extensively studied polymorphism among all CTLA-4 genetic variants and contributions to increasing the likelihood of developing cancer are well known in various populations, especially Asians. However, there have hiterto been no data with respect to the effect of this polymorphism on breast cancer susceptibility in our North Indian population. We therefore assayed genomic DNA of 250 breast cancer subjects and an equal number of age-, sex- and ethnicity-matched healthy controls for the CTLA-4 +49 G/A polymorphism but no significant differences in either the gene or allele frequency were found. Thus the CTLA-4 +49 G/A polymorphism may be associated with breast cancer in other Asians, but it appears to have no such effect in North Indians. The study also highlights the importance of conducting genetic association studies in different ethnic populations. -
Liu, Ju;Shu, Tong;Chang, Sheng;Sun, Ping;Zhu, Hui;Li, Huai 2039
This study was conducted in order to obtain a screening and early detection reference for children whose mothers had been diagnosed with cancer. Data for 276 mother-child pairs with malignant tumors were analyzed. The distribution of cancers in affected families was generally similar to that of the general Chinese population, and correspondingly breast cancer was the most common malignancy amongst daughters whose mother had cancer (32.7%). The most prevalent cancer amongst sons with affected mothers was gastric cancer, rather than lung cancer. Daughters were more likely to have the same kind of malignant tumor as their mother (P<0.05), and were more likely to develop breast cancer than any other malignant disease if their mother had a breast tumor (P<0.0001). Likewise, if the mother was diagnosed with breast or gynecological cancer, the daughter was more likely to be diagnosed with breast or gynecological cancer than any other cancer (P<0.01). Daughters and sons developed malignant diseases 11 and 6.5 years earlier than their mothers, respectively (P<0.0001).Women with a mother who suffered cancer should be screened for malignancy from 40 years of age especially for breast, lung, and gynecological cancers. For men with affected mothers, screening should start when they are 45 years old focusing particularly on lung and digestive system cancers. -
Akkuzu, Gulcihan;Talas, Melek Serpil;Ortac, Firat 2045
Background: Functional status is the ability to perform daily activities. Little is known about quality of life and health status of gynaecological cancer patients. The present study therefore aimed to evaluate the functional status of women receiving treatment for gynecological oncological disease while not hospitalised. Materials and Methods: This descriptive study covered 42 patients monitored by the Gynecological Oncology Unit in 2011. Data were collected using the Functional Living Index-Cancer and analysed with the chi square test, independent samples t-test, Mann-Whitney U test, one-way ANOVA test and the Kruskal-Wallis H test. Results: Of the 42 cases, 66.7% had been diagnosed within the previous year and 90.5% were undergoing chemotherapy. The most severe symptoms experienced were pain (35.7%), fatigue-weakness (40.5%) and nausea and vomiting (56.5%). Daily activities where the most difficulty was experienced were housework (28.6%), average pace walking (31.0%), carrying more than 5 kg (28.6%). The mean Functional Living Index score was quite high ($103.5{\pm}24.1$ ). FLIC-C scale scores did not vary with the educational status, diagnosis duration, and family history of cancer (p>0.05). Conclusions: Evaluation of the functional status of gynecological cancer patients and how they cope with problems should indicate to healthcare professionals what help can be given to maintain quality of life. -
Performance of Siriraj Liquid-Based Cytology: a Single Center Report Concerning over 100,000 SamplesSangkarat, Suthi;Laiwejpithaya, Somsak;Rattanachaiyanont, Manee;Chaopotong, Pattama;Benjapibal, Mongkol;Wongtiraporn, Weerasak;Laiwejpithaya, Sujera 2051
Background: To evaluate the performance of Siriraj liquid-based cytology (LBC) for cervical neoplasia screening after increasing use of this technology. Materials and Methods: Cytological reports of 103,057 Siriraj-LBC specimens obtained in 2007-2009 were compared with those of 23,676 specimens obtained in 2006. Results: Comparing with the year 2006, the 2007-2009 patients were slightly older ($43.4{\pm}12.yr$ vs$42.7{\pm}12.2yr$ , p <0.001), and their specimens had much lower proportion of unsatisfactory slides (OR=0.06, 95%CI 0.04-0.09) with comparable detection rates (3.96% vs 3.70%, p=0.052) but different proportions of various cytological abnormalities (p<0.001). The 2007-2009 Siriraj-LBC had a negative predictive value (NPV) for cervical intraepithelial neoplasia 2+ (CIN2+) of 97.6% and an overall positive predictive value (PPV) of 43.9%. The PPV for CIN2+ varied with types of abnormal cytology, from 13.7% to 93.8% in atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells cannot exclude HSIL (ASC-H), high-grade squamous intraepithelial lesion (HSIL), atypical glandular cells (AGC), to squamous cell carcinoma (SCC), respectively. The PPVs for CIN2+ in ASCUS and LSIL were comparable, but the PPV for CIN1 was higher for LSIL than for ASCUS (41.63% vs 16.32%). Conclusions: Siriraj-LBC has demonstrated a stable detection rate and NPV for CIN2+ of >95% since the first year of use. The comparable PPVs for CIN2+ of ASCUS and LSIL suggests that these two conditions may undergo similar management; other cytological abnormalities need immediate evaluation. -
Zhao, Chang;Wang, Xu-Jie;Wang, Song;Feng, Wei-Hua;Shi, Lei;Yu, Chun-Peng 2057
Purpose: To assess the effect and safety of lobaplatin combinated floxuridine /pirarubicin in transcatheter hepatic arterial chemoembolization(TACE) of unresectable primary liver cancer. Patients and Methods: TACE combined with the chemotherapy regimen was used to treat 34 unresectable primary liver cancer patients. DSA/MRI/CT/blood routine examinations were used to evaluate short term activity and toxicity after 4-5 weeks, the process being repeated if necessary. Results: Among the 34 cases, 1 (2.9%) showed a complete response, 21 (61.7%) a partial response, 8 (23.5%) stable disease, and 4 progressive disease, with a total effective rate of 67.6%. The content of alpha fetoprotein dropped by over 50% in 20 cases (58.8%). The rate of recovery was hepatalgia (88.2%), ascites (47.1%), appetite (55.9%), Performance Status(30.4%). The median follow-up time (MFT) was 281 days (63-558 days), and median progression-free survival was 118.5 days (95%, CI:88.8-148.2days). Adverse reactions (III-IV grade) were not common, with only 4 cases of vomiting and 2 cases of thrombocytopenia (III grade). Conclusions: Lobaplatin-based TACE is an effective and safe treatment for primary liver cancer. -
Cihan, Yasemin Benderli;Ozturk, Ahmet;Mutlu, Hasan 2061
Background: It has been demonstrated that neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios are associated with prognosis in cancer patients. The aim of this study was to investigate whether pretreatment white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, basophil and eosinophil counts, LDH level, NLR and PLR are associated with prognosis in patients with malignant pleural mesothelioma (MPM). Materials and Methods: We retrospectively reviewed files of 50 patients who were managed with a diagnosis of MPM between 2005 and 2010. Demographic and clinical characteristics, treatments, response to treatment and prognostic factors were evaluated, along with relationships between pretreatment blood parameters and prognosis. Results: Overall, 38 men and 12 women were included to the study. Mean age was$61.5{\pm}9.4$ years (range: 39-83 years). There was advanced disease in 86% (n=43) and the histological type was epithelial mesothelioma in the majority (82%). Of the cases, 17 (34%) received radiotherapy, while 42 cases underwent first- and second-line chemotherapy, with cisplatin plus pemetrexed as the most commonly used regimen. In the assessment after therapy, it was found that there was complete response in 4 cases (8%), partial response in 10 cases (20%), stable disease in 17 cases (34%) and progression in 19 cases (38%). Median follow-up was 10 months (range: 10 day-30 months). Median overall survival was found to be 20.7 months while median progression-free survival as 10 months. In univariate and multivariate analyses, it was found that factors significantly affecting overall survival included stage (p=0.030), response to treatment (p=0.026) and monocyte count (p=0.004), while factors affecting disease-free survival included NLR (p=0.018), response to treatment (p=0.001), and PLR score (p=0.003). Conclusions: Overall and disease-free survival was found to be better in cases with a WBC count<8.000, platelet count<300,000, and low NLR and PLR scores in malignant pleural mesothelioma. -
Sengul, Demet;Altinay, Serdar;Oksuz, Hulya;Demirturk, Hanife;Korkmazer, Engin 2069
Purpose: To appraise the frequency of cervical cytological abnormalities in a population at normal risk via analysing the archive records of cytology for the period of approximately 9,5 years, comparing them with patient demographic charecteristics, and discuss the results for women under age of 35. Materials and Methods: A total of 32,578 cases of Pap smears were retrieved and analysed from our archive included the Pap tests performed between January 2001 and April 2010 at the Early Cancer Screening, Diagnosing and Education Center by the consent of three pathologists via utilizing the Bethesda System Criteria 2001 and the results were compared with some demographical characteristics. Results: Our rate of the cervical cytological abnormality was 1.83%, with ASCUS in 1.18%, LSIL in 0.39, HSIL in 0.16%, AGUS in 0.07%, squamous cell carcinoma in 0.02%, and adenoarcinoma in 0.006%. Cytological abnormalities were detected mostly in those with higher age, lower parity, and premenopausal period whereas the smoking status was without influence. Bacterial vaginosis (5.6%) was the most frequent infectious finding (Candida albicans 2.7%; Actinomyces sp. 1.3%; and Trichomonas vaginalis 0.2%) detected on the smears. The rate of abnormal cervical cytology was 9.5% among the women aged between 30-34. Conclusions: Early detection of the cervical abnormalities by means of the regular cervical cancer screening programmes is useful to attenuate the incidence, mortality, and morbidity of cervical cancer. Our prevalence of the cytological abnormalities was much lower than the one in Western populations in general but very similar to those reported from other Islamic countries that may be explained by the conservative lifestyle and the lower prevalence of HPV in Turkey. A remarkable rate of abnormal cervical cytology of women aged 30-34 was pointed out in the present study. -
Tang, Zhen-Hai;Zhang, Chi;Cheng, Pan;Sun, Hong-Min;Jin, Yu;Chen, Yuan-Jing;Huang, Fen 2075
The association between glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1) and risk of acute leukemia in Asians remains controversial. This study was therefore designed to evaluate the precise association in 23 studies identified by a search of PubMed and several other databases, up to December 2013. Using random or fixed effects models odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Heterogeneity across studies was assessed, and funnel plots were constructed to test for publication bias. The meta-analysis showed positive associations between GST polymorphisms (GSTM1 and GSTT1 but not GSTP1) and acute leukemia risk [(OR=1.47, 95% CI 1.18-1.83); (OR=1.32, 95% CI 1.07-1.62); (OR=1.01, 95% CI 0.84-1.23), respectively] and heterogeneity between the studies. The results suggested that the GSTM1 null genotype and GSTT1null genotype, but not the GSTP1 polymorphism, might be a potential risk factors for acute leukemia. Further well-designed studies are needed to confirm our findings. -
Abdel-Rahman, Wael Mohamed;Nieminen, Taina Tuulikki;Shoman, Soheir;Eissa, Saad;Peltomaki, Paivi 2083
Colorectal cancers remain to be a common cause of cancer-related death. Early-onset cases as well as those of various ethnic origins have aggressive clinical features, the basis of which requires further exploration. The aim of this work was to examine the expression patterns of$p15^{INK4b}$ and SMAD4 in colorectal carcinoma of different ethnic origins. Fifty-five sporadic colorectal carcinoma of Egyptian origin, 25 of which were early onset, and 54 cancers of Finnish origin were immunohistochemically stained with antibodies against$p15^{INK4b}$ and SMAD4 proteins. Data were compared to the methylation status of the$p15^{INK4b}$ gene promotor.$p15^{INK4b}$ was totally lost or deficient (lost in${\geq}50%$ of tumor cell) in 47/55 (85%) tumors of Egyptian origin as compared to 6/50 (12%) tumors of Finnish origin (p=7e-15). In the Egyptian cases with$p15^{INK4b}$ loss and available$p15^{INK4b}$ promotor methylation status, 89% of cases which lost$p15^{INK4b}$ expression were associated with$p15^{INK4b}$ gene promotor hypermethylation. SMAD4 was lost or deficient in 25/54 (46%) tumors of Egyptian origin and 28/48 (58%) tumors of Finnish origin. 22/54 (41%) Egyptian tumors showed combined loss/deficiency of both$p15^{INK4b}$ and SMAD4, while$p15^{INK4b}$ was selectively lost/deficient with positive SMAD4 expression in 24/54 (44%) tumors. Loss of$p15^{INK4b}$ was associated with older age at presentation (>50 years) in the Egyptian tumors (p=0.04). These data show for the first time that$p15^{INK4b}$ loss of expression marks a subset of colorectal cancers and ethnic origin may play a role in this selection. In a substantial number of cases, the loss was independent of SMAD4 but rather associated with$p15^{INK4b}$ gene promotor hypermethylation and old age which could be related to different environmental exposures. -
Kacan, Turgut;Babacan, Nalan Akgul;Seker, Metin;Yucel, Birsen;Bahceci, Aykut;Eren, Ayfer Ay;Eren, Memet Fuat;Kilickap, Saadettin 2089
Background: Although many prognostic factors have been identified for lung cancers, new ones are needed to determine the course of the disease. Recently, a high neutrophil to lymphocyte ratio (NLR) prior to surgery or treatment has been shown to be an indicator of prognosis for cancer. The aim of this study was to investigate the value of NLR as a prognostic factor and the correlation between NLR and other probable clinical prognostic factors in non small cell lung cancer patients prior to treatment. Materials and Methods: Data of patients who were diagnosed with non-small cell lung cancer in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR was calculated before the application of any treatment. Results: A total of 299 patients, 270 (90%) males and 29 (10%) females, were included in the study. Age (p<0.001) stage (p<0.001), Eastern Cooperative Oncology Group performance status (p<0.001), weight loss (p<0.001), anemia (p<0.001), histopatology (p<0.001), NLR${\geq}3$ (p=0.048), NLR${\geq}4$ (p=0.025) and NLR${\geq}5$ (p=0.018) were found to be the prognostic factors. Age, anemia, Eastern Cooperative Oncology Group performance status, the stage, NLR (${\geq}5$ ) were an independent prognostic factors. There was a positive correlation between NLR and the Eastern Cooperative Oncology Group performance status (0.23, p=0.001), the C reactive protein levels (r=0.36, p<0.001). Conclusions: Prior to treatment high NLR was found as an independent poor prognosis factor. Besides, NLR correlated with Eastern Cooperative Oncology Group performance status and the C reactive protein levels. -
Gong, Dan-Dan;Man, Chang-Feng;Xu, Juan;Fan, Yu 2095
Objective: Most patients with advanced breast cancer experience resistance to endocrine treatment and eventual disease progression. This meta-analysis was designed to compare the efficacy and tolerability of fulvestrant 250mg with anastrozole 1mg in postmenopausal women with advanced breast cancer. Methods: Electronic literature databases (Cochrane Library, Medline, and Embase) were searched for randomized controlled trials (RCTs) published prior to August 2013. Only RCTs that compared fulvestrant 250mg to anastrozole 1mg in postmenopausal women with advanced breast cancer were selected. The main outcomes were time to treatment failure (TTF), time to progression (TTP), duration of response (DOR), clinical benefit rate, and tolerability. Results: Four RCTs covering 1,226 patients (fulvestrant, n=621; anastrozole, n=605) were included in the meta-analysis. Fulvestrant increased the DOR compared to anastrozole (HR =1.31, 95% confidence interval [CI] 1.13-1.51). There was no statistically significant difference between fulvestrant and anastrozole in terms of TTF (HR=1.02, 95%CI 0.89-1.17), complete response (RR=1.79, 95%CI, 0.93-3.43), and partial response (RR=0.91, 95%CI 0.69-1.21). As for safety, there was no statistical significance between the two groups for common adverse events. Conclusion: Fulvestrant 250mg is as effective and well-tolerated as anastrozole 1mg treatment for advanced breast cancer in postmenopausal women whose disease progressed after prior endocrine treatment. Thus, fulvestrant may serve as a reasonable alternative to anastrozole when resistance is experienced in breast cancer cases. -
Parlayan, Cuneyd;Ikeda, Shinobu;Sato, Noriko;Sawabe, Motoji;Muramatsu, Masaaki;Arai, Tomio 2101
Background: Single nucleotide polymorphisms (SNPs) affecting microRNA (miR) sequences may influence carcinogenesis. Our current study primarily aimed to confirm previously conducted association studies between rs2910164 found on miR-146a, and rs11614913 located on miR-196a2 polymorphisms and cancer phenotypes in the Japanese elderly population. rs2910164 (G/C) and rs11614913 (T/C) polymorphisms were determined by genotyping on the samples collected from 1,351 consecutive autopsy cases registered in the Japanese SNPs for geriatric research (JG-SNP) data base. Cancer samples were systematically reviewed, pathologically verified and assessed with respect to miR-146a and miR-196a2 genotypic variation. The current study covered 726 males and 625 females with a mean age of$80.3{\pm}8.9$ years. The study included 524 subjects without cancer and 827 subjects with at least one type of cancer, such as gastric (n=160), lung (n=148), colorectal (n=116) or others. Males with cancers (n=467) were more numerous than females (n=360). Both rs11614913 (CT: TT adjusted odds ratio (OR) 95% confidence interval (95%CI)=0.98 (0.75-1.28), p=0.873, CC: TT adjusted OR (95%CI)=1.06 (0.76-1.47), p=0.737, CT+CC: TT, adjusted OR (95%CI)=0.99 (0.77-1.29), p=0.990), and rs2910164 (CG: CC adjusted OR (95%CI)=1.12 (0.87-1.44), p=0.383, GG: CC adjusted OR (95%CI)=1.03 (0.71-1.48), p=0.887, CG+GG: CC adjusted OR (95%CI)=1.10 (0.87-1.39), p=0.446) polymorphisms did not show significant association with overall cancer in all subjects. However, "CC" genotype in rs11614913 polymorphism was significantly associated with increased gastric cancer (n=160) in all subjects (CC: CT+TT, adjusted OR (95%CI)=1.50 (1.02-2.22), p=0.040). We found that rs11614913 and rs2910164 do not pose general cancer risk, but rs11614913 may influence gastric cancer in Japanese elderly population. Confirmation of our study results requires further investigations with larger subject populations. -
Background: The aim of this planned research was to determine the comfort and anxiety levels of women with breast cancer receiving radiotherapy. Materials and Methods: This descriptive type study covered patients that applied to the radiation oncology breast polyclinic of our university hospital between January and May 2011. Patient Identification Form, Radiation Therapy Comfort Questionnaire (RTCQ), Spielberger State Trait Anxiety Inventory (STAI) were completed and analysed. Results: The mean age of the women who participated in the study was
$51.6{\pm}10.4$ years. Mean scores of women were$3.73{\pm}0.31$ for RTCQ,$29.1{\pm}5.88$ for SAI and$37.8{\pm}6.91$ for TAI. While the comfort levels of the women with breast cancer receiving radiotherapy were moderate, they experienced only low levels of anxiety. Conclusions: By determining the comfort level of the patient before radiotherapy, besides providing comfort in this direction, eliminating/minimizing anxiety and stress will positively affect radiotherapy application. More attention of nurses to this issue is to be recommended. -
Zhao, Ji-An;Peng, Li;Geng, Cui-Zhi;Liu, Yue-Ping;Wang, Xu;Yang, Hui-Chai;Wang, Shi-Jie 2115
The purpose of the present study was to evaluate the preventive effects of hydrazinocurcumin (HZC) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in a male Sprague Dawley (SD) rat model. One hundred and twenty male SD rats used in this study were divided into six groups. Those receiving DEN with curcumin (CUR) or HZC were studied compared with the DEN-alone group. The study demonstrated that DEN induced severe histological and immunohistochemical changes in liver tissues, significantly increasing the levels of liver marker enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP),${\gamma}$ -glutamyltransferase (GGT) and total bilirubin level (TBL)). The hepatocarcinoma incidences were 100.0%, 36.7% and 20.0% in the DEN-alone, DEN-CUR and DEN-HZC groups, respectively. Although macroscopic and microscopic features suggested that both CUR and HZC were effective in inhibiting DEN-induced hepatocarcinogenesis, HZC was exerted a stronger influence. Immunohistochemical analysis with PCNA demonstrated significantly differences among the groups (all P < 0.05). Taken together, the results suggested application of CUR and HZC could prevent the occurrence of carcinogenesis and HZC may be a more potent compound for prevention of DEN-induced hepatocarcinogenesis in rats than CUR. -
Matin, Maryam Moghaddam;Nakhaeizadeh, Hossein;Bahrami, Ahamd Reza;Iranshahi, Mehrdad;Arghiani, Nahid;Rassouli, Fatemeh Behnam 2123
A current hurdle in cancer management is the intrinsic or acquired resistance of cancer cells to chemical agents that restricts the efficacy of therapeutic strategies. Accordingly, there is an increasing desire to discover new natural compounds with selective toxicity to combat malignancies. In present study, the cytotoxic and apoptosis-inducing activities of ferutinin, a terpenoid derivative from Ferula ovina, were investigated on human breast (MCF7) and bladder (TCC) cancer cells as well as normal fibroblasts (HFF3).The toxicity and DNA damage inducing effects of ferutinin were studied by MTT and comet assays, DAPI and PI staining and DNA laddering. The$IC_{50}$ values of ferutinin were identified and compared with routine prescribed drugs, doxorubicin and vincristine, by MTT test. Alkaline comet assay and DAPI staining revealed DNA damage due to ferutinin, which was significantly (p<0.001) higher in MCF7 and TCC than HFF3 cells. Apoptosis induction was evidenced by PI staining and DNA laddering. Our results suggest that ferutinin could be considered as an effective anticancer agent for future in vivo and clinical experiments. -
Background: Cervical cancer is one of the most common female malignancies with high mortality rates in developing countries. Our purpose was to determine the prevalence of cervical cytological abnormalities by cervical cytology (CC) and the analysis of risk factors in Albanian population. Materials and Methods: A total of 5,416 conventional pap smear tests collected between January 2009 and January 2012 from Tirana University Hospital Obstetrics-Gynecology "Queen Geraldine" were retrospectively analyzed. Results: A total of 258 (4.8%) cases had epithelial abnormalities. The numbers and rates were as follows: atypical squamous cell of undetermined significance (ASCUS; n=150 [2.76%]); atypical glandular cells of undetermined significance (AGUS; n=8 [0.14%]); low-grade squamous intraepithelial lesion (LSIL; n=87 [1.6%]); high- grade squamous intraepithelial lesion (HSIL; n=10 [0.18%]); and squamous cell carcinoma (SCC; n=3 [0.05%]). Conclusions: The prevalence of cervical cytological abnormality in our study was 4.8%. A larger community-based study may establish the exact prevalence of malignant and premalignant lesions, so as to plan for future screening.
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Wang, Nan;Wang, Wei;Huo, Po;Liu, Cai-Qin;Jin, Jian-Chang;Shen, Lian-Qing 2133
4-Methylsulfinyl-3-butenyl isothiocyanate (MTBITC) found in the radish (Raphanus sativus L.), is a wellknown anticancer agent. In this study, the mechanisms of the MTBITC induction of cell apoptosis in human A549 lung cancer cells were investigated. Our PI staining results showed that MTBITC treatment significantly increased the apoptotic sub-G1 fraction in a dose-dependent manner. The mechanism of apoptosis induced by MTBITC was investigated by testing the change of mitochondrial membrane potential (${\Delta}{\Psi}m$ ), the expression of mRNAs of apoptosis-related genes by RT-PCR, and the activities of caspase-3 and -9 by caspase colorimetric assay. MTBITC treatment decreased mitochondrial membrane potential by down-regulating the rate of Bcl-2/Bax and Bcl-xL/Bax, and activation of caspase-3 and -9. Therefore, mitochondrial pathway and Bcl-2 gene family could be involved in the mechanisms of A549 cell apoptosis induced by MTBITC. -
Etemadi, Mehrnoosh;Pourian, Mandana;Shakib, Asyeh;Sabokbar, Tayebeh;Peyghanbari, Vahideh;Shirkoohi, Reza 2141
Background: Gastric cancer is the second most common cause of cancer death. It has a poor prognosis with only 5-10% of hereditary etiology. If it is diagnosed, it could be helpful for screening the other susceptible members of a family for preventive procedures. Usually it is identified by symptoms such as presence of cancer in different members of family, some special type of pathology such as diffused adenocarcinoma, having younger age and multiple cancer syndromes. Hence, designing a registry program can be a more practical way to screen high risk families for a preventive program. Materials and Methods: Based on the inclusion criteria, a questionnaire was prepared. After pilot on a small number of patients, the actual data was collected from 197 patients and processed in SPSS 16.0. Results: Totally, 11.8% of the patients were younger than 45 years old. Blood type 'A' was dominant and males had a higher risk behavior with higher consumption of unhealthy food. Adenocarcinoma was reported in majority of cases. 21.8% of the patients had the including criteria for familial gastric cancer (FGC). Conclusions: The high percentage of FGC population compared to the other studies have revealed a need to design an infrastructural diagnostic protocol and screening program for patients with FGC, plus preventive program for family members at risk which could be done by a precise survey related to frequency and founder mutations of FGC in a national registry program. -
Chan, Siew Wui;Kallarakkal, Thomas George;Abraham, Mannil Thomas 2145
Background: The survival rate for oral squamous cell carcinoma (OSCC) has remained generally unchanged in the past three decades, underlining the need for more biomarkers to be developed to aid prognostication and effective management. The prognostic potential of E-cadherin expression in OSCCs has been variable in previous studies while galectin-9 expression has been correlated with improved prognosis in other cancers. The aim of the present study was to investigate the expression of galectin-9 and E-cadherin in OSCC and their potential as prognostic biomarkers. Materials and Methods: E-cadherin and Galectin-9 expression was examined by immunohistochemistry in 32 cases of OSCC of the buccal mucosa (13 with and 19 without lymph node metastasis), as well as 6 samples of reactive lesions and 5 of normal buccal mucosa. Results: The expression of E-cadherin in OSCC was significantly lower than the control tissues but galectin-9 expression was conversely higher. Median E-cadherin HSCOREs between OSCCs positive and negative for nodal metastasis were not significantly different. Mean HSCOREs for galectin-9 in OSCC without lymph node metastasis ($127.7{\pm}81.8$ ) was higher than OSCC with lymph node metastasis ($97.9{\pm}62.9$ ) but this difference was not statistically significant. Conclusions: E-cadherin expression is reduced whilst galectin-9 expression is increased in OSCC. However, the present results suggest that E-cadherin and galectin-9 expression may not be useful as prognostic markers for OSCC. -
Niu, Yu-Na;Liu, Qing-Qing;Zhang, Su-Ping;Yuan, Na;Cao, Yan;Cai, Jin-Yang;Lin, Wei-Wei;Xu, Fei;Wang, Zhi-Jian;Chen, Bo;Wang, Jian-Rong 2153
Beclin 1 is a key factor for initiation and regulation of autophagy, which is a cellular catabolic process involved in tumorigenesis. To investigate the role of alternative splicing of Beclin1 in the regulation of autophagy in leukemia cells, Beclin1 mRNA from 6 different types of cell lines and peripheral blood mononuclear cells from 2 healthy volunteers was reversely transcribed, subcloned, and screened for alternative splicing. New transcript variants were analyzed by DNA sequencing. A transcript variant of Beclin 1 gene carrying a deletion of exon 11, which encoded a C-terminal truncation of Beclin 1 isoform, was found. The alternative isoform was assessed by bioinformatics, immunoblotting and subcellular localization. The results showed that this variable transcript is generated by alternative 3' splicing, and its translational product displayed a reduced activity in induction of autophagy by starvation, indicating that the spliced isoform might function as a dominant negative modulator of autophagy. Our findings suggest that the alternative splicing of Beclin 1 might play important roles in leukemogenesis regulated by autophagy. -
Askari, Faezeh;Parizi, Mehdi Kardoust;Jessri, Mahsa;Rashidkhani, Bahram 2159
Background: Prostate cancer is the most frequently occurring cancer among males in economically developed countries. Among the several risk factors that have been suggested, only age, ethnicity, diabetes, and family history of prostate cancer are well-established and primary prevention of this disease is limited. Prior studies had shown that dietary intake could be modified to reduce cancer risk. We conducted a hospital-based, casecontrol study to examine the association between dietary patterns and prostate cancer risk in Iran. Materials and Methods: A total of fifty patients with prostate cancer and a hundred controls underwent face-to-face interviews. Factor analysis was used to determine the dietary patterns. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: We defined two major dietary patterns in this population: 'western diet'(high in sweets and desserts, organ meat, snacks, tea and coffee, French fries, salt, carbonated drinks, red or processed meat) and 'healthy diet' (high in legumes, fish, dairy products, fruits and fruit juice, vegetables, boiled potatoes, whole cereal and egg). Both Healthy and western pattern scores were divided into two categories (based on medians). Higher scores on Healthy pattern was marginally significantly related to decreased risk of prostate cancer (above median vs below median, OR =0.4, 95%CI=0.2-1.0). An increased risk of prostate cancer was observed with the higher scores on the Western pattern (above median vs below median, OR=4.0, 95%CI=1.5-11.0). Conclusions: The results of this study suggested that diet might be associated with prostate cancer among Iranian males. -
Uysal-Sonmez, Ozlem;Tanriverdi, Ozgur;Uyeturk, Ummugul;Budakoglu, Isil Irem;Kazancioglu, Rumeyza;Turker, Ibrahim;Budakoglu, Burcin;Yalcintas-Arslan, Ulku;Oksuzoglu, Berna 2165
Background: Today, survival rate of patients with chronic renal failure/hemodialysis has increased so that chronic illnesses are more likely to occur. Cancer is the main cause of morbidity and mortality in such patients. Aim: In this study, physician attitudes were examined about cancer screening in patients with renal failure. Materials and Methods: This study was done by face to face questionnaire in the$27^{th}$ National Nephrology Congress to determine if the physicians dealing with chronic renal failure, hemodialysis or renal transplanted patients, recommend cancer screening or not and the methods of screening for cervix, prostate, breast and colon cancer. Results: One hundred and fifty six physicians were included in the survey. A total of 105 (67%) participants were male and the age of responders was$48{\pm}9$ years. About 29% were specialists in nephrology, 28% internal medicine, and 5% were other areas of expertise. Some 48% of participants were hemodialysis certified general practitioners. Patients were grouped as compensated chronic renal failure, hemodialysis or renal transplanted. Of the 156 responders, 128 (82%) physicians recommended breast cancer screening and the most recommended subgroup was hemodialysis patients (15%). The most preferred methods of screening were combinations of mammography, self breast examination and physicianbreast examination. 112 (72%) physicians recommended cervix cancer screening, and the most preferred method of screening was pap-smear. Colon cancer screening was recommended by 102 (65%) physicians and prostate screening by 109 (70%) physicians. The most preferred methods of screening were fecal occult blood test and PSA plus rectal digital test, respectively. Conclusions: It is not obvious whether cancer screening in renal failure patients is different from the rest of society. There is a variety of screening methods. An answer can be found to these questions as a result of studies by a common follow-up protocol and cooperation of nephrologists and oncologists. -
Liu, Yong-Qi;Li, Yi;Qin, Jie;Wang, Qian;She, Ya-Li;Luo, Ya-Li;He, Jian-Xin;Li, Jing-Ya;Xie, Xiao-Dong 2169
Matrine, a main active component extracted from dry roots of Sophora flavecens, has been reported to exert antitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. To determine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays were employed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells following staining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determined expression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNA profiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and timedependent manner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1 phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reduction in the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549 cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared with untreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing useful information for understanding anticancer mechanisms. -
Soleyman-Jahi, Saeed;Zendehdel, Kazem;Akbarzadeh, Kambiz;Haddadi, Mahnaz;Amanpour, Saeid;Muhammadnejad, Samad 2179
Background: In vitro, in vivo and clinical studies have demonstrated anti-cancer effects of deuterium depleted water (DDW). The nature of this agents action, cytotoxic or cytostatic, remains to be elucidated. We here aimed to address the point by examining effects on different cell lines. Materials and Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) -based cytotoxicity analysis was conducted for human breast, stomach, colon, prostate cancer and glioblastoma multiforme cell lines as well as human dermal fibroblasts. The cell lines were treated with decreasing deuterium concentrations of DDW alone, paclitaxel alone and both. One way analysis of variance (ANOVA) was used for statistical analysis. Results: Treatment with different deuterium concentrations of DDW alone did not impose any significant inhibitory effects on growth of cell lines. Paclitaxel significantly decreased the survival fractions of all cell lines. DDW augmented paclitaxel inhibitory effects on breast, prostate, stomach cancer and glioblastoma cell lines, with influence being more pronounced in breast and prostate cases. Conclusions: DDW per se does not appear to have inhibitory effects on the assessed tumor cell lines as well as normal fibroblasts. As an adjuvant, however, DDW augmented inhibitory effects of paclitaxel and thus it could be considered as an adjuvant to conventional anticancer agents in future trials. -
Bansal, Anshuma;Patel, Firuza Darius;Rai, Bhavana;Dhanireddy, Bhaswanth;Sharma, Suresh Chand 2185
Chemotherapy has significantly improved the prognosis of cancer patients with various malignancies. However, female patients, especially those whoich are premenopausal, suffer from significant chemotherapy induced ovarian function impairment, which decreases their quality of life. Many new techniques for ovarian preservation have been established in recent years. Although the use of gonadotrophin releasing hormone analogues (GnRHa) for this purpose is not a new concept, its effectiveness in protection of ovarian function is still debatable. This article deals with studies and metaanalyses which have been undertaken in the past, demonstrating the impact of GnRHa in ovarian function preservation, and whether their use can be implemented in routine practice. -
Zhang, En;Cao, Wei;Cheng, Chong;Huo, Bin-Liang;Wang, Yong-Heng 2191
Background: Fluorouracil-based regimens have been widely accepted and recommended in the guidelines for treating patients with early or advanced staged colon cancer, although results are controversial. Here we performed a systemic analysis to evaluate the impact of S-1 based regimens on response and survival of patients with colon cancer. Methods: Clinical studies evaluating the impact of S-1 based regimens on response and survival of patients with colon cancer were identified using a predefined search strategy. Summary response rates (RRs) to treatment were calculated. Results: Six clinical studies which including 227 patients with advanced colorectal cancer were considered eligible for inclusion. Two studies were conducted using combination of S-1 and Oxaliplatin, and four studies featured S-1 and irinotecan. Systemic analysis showed that, in all patients, pooled RRs was 43.17%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. No treatment related death occurred. Conclusion: This systemic analysis suggests that S-1 based regimens, both with oxaliplatin or irinotean are associated with acceptable response and toxicity in patients with colon cancer. -
Iqbal, Hassan;Bhatti, Abu Bakar Hafeez;Hussain, Raza;Jamshed, Arif 2195
Background: Despite being rare in incidence, malignant tumors of major salivary glands show diverse histological variation. There are limited data on major salivary gland tumor management and outcome from Pakistan. The objective of this study was to share our experience with management of malignant tumors of major salivary glands. Materials and Methods: Patients who received treatment at Shaukat Khanum Cancer Hospital and Research Center from July 2002 to June 2011 with an underlying diagnosis of a major salivary gland malignancy were included. Patient characteristics and treatment modalities were assessed. Local, regional and distant failures were determined. Disease free survival (DFS) and overall survival (OS) were calculated using Kaplan Meier curves and the Log rank test was used to determine statistical significance. Univariate and multivariate analyses were performed using Cox proportional hazard regression. Results: The parotid gland was the primary site of origin in 104 (80%) patients. Mucoepidermoid carcinoma (43%) and adenoid cystic carcinoma (24%) were the most common histological types. Surgery followed by adjuvant radiation remained the mainstay treatment modality with 81 (62%) patients. Nineteen (15%) patients were treated with surgery alone and 30 (23%) patients with locally advanced surgically inoperable tumors received radiation only. Forty one (32%) patients failed the treatment (local 12, regional 11, locoregional 5, distant 13). The expected 5 year DFS and OS were 65% and 74% respectively. On multivariate analysis, grade was the only independent predictor of DFS and nodal involvement was the only independent predictor of overall survival. Conclusions: Employing existing standards of treatment, comparable survival can be achieved in Pakistani population with major salivary gland malignancies as elsehwere in the world. -
Gyrylova, Svetlana Nikolaevna;Aksenenko, Mariya Borisovna;Gavrilyuk, Dmitriy Vladimirovich;Palkina, Nadezda Vladimirovna;Dyhno, Yuriy Alexandrovich;Ruksha, Tatiana Gennadievna;Artyukhov, Ivan Pavlovich 2201
Russian rates for melanoma incidence and mortality are relatively low as compared to some other white populations but the tumor is of increasing importance. In this paper, data are based on a retrospective descriptive analysis of melanoma epidemiology and clinicopathological characteristics in Krasnoyarsk Territory belonging to the Siberian Federal District of the Russian Federation. The age-adjusted incidence and mortality rates for the period 1996-2009 were determined with subsequent retrospective analysis of clinicopathological data of 103 primary melanoma cases. Our results showed that incidence and mortality rates in the region under consideration match the Russian national trends and correspond to epidemiological data of the countries of Eastern Europe. Stratification of melanoma cases by age, sex, clinicopathological state and localization revealed a prevalence of lesions on the trunk and lower extremities. Most melanomas diagnosed were of superficial spreading type and the third Clark's level of tumor invasion and stage II according to AJCC. In spite of comparatively low rates of incidence and mortality the trend to increase of melanoma cases in the region under consideration obviously calls for more attention and further investigation. -
Wu, Bai-Shou;Hu, Yi;Sun, Jing;Wang, Jin-Liang;Wang, Peng;Dong, Wei-Wei;Tao, Hai-Tao;Gao, Wen-Juan 2205
Objective: To retrospectively review the clinical characteristics and analyze the prognostic factors of Chinese patients with pulmonary neuroendocrine tumors. Materials and Methods: The clinical data of 176 patients with pulmonary neuroendocrine tumors in Chinese PLA General Hospital from Mar., 2000 to Oct., 2012 were retrospectively analyzed. The parameters were evaluated by univariate and multivariate analysis, including the gender, age, smoking history, family history, TNM staging, localization (central or peripheral), tumor size, nodal status, histological subtype and treatment (operation or non-operation). Results: There were 23 patients with typical carcinoids (TC) (13.1%), 41 with atypical carcinoids (AC) (23.3%), 10 with large cell neuroendocrine carcinoma (LCNEC) (5.7%) and 102 with small cell lung cancer (SCLC) (57.9%). The median follow-up time was 64.5 months for AC, 38 months for LCNEC and 27 months for SCLC. The typical carcinoid censored data was 18 (more than 50% of the patients), so the median follow-up time was not obtained, and actuarial 5-year survivals for TC, AC, LCNEC and SCLC were 75.1%, 51.7%, 26.7% and 38.8%, respectively. COX univariate analysis revealed that the age (P=0.001), histological subtype (P=0.005), nodal status (P=0.000), treatment (P=0.000) and TNM staging (P=0.000) were the prognostic factors of the patients with pulmonary neuroendocrine tumors, whereas its multivariate analysis showed that only the age(P=0.001), TNM staging (P=0.002) and treatment (P=0.000) were independent prognostic factors. Conclusions: Radical surgery remains the treatment of choice, and is the only curative option. The age, TNM staging and treatment are confirmed to be the independent prognostic factors in multivariable models for pulmonary neuroendocrine tumors. -
Sethasathien, Sethawat;Charoenkwan, Kittipat;Settakorn, Jongkolnee;Srisomboon, Jatupol 2211
Background: To examine the incidence of positive vaginal surgical margins and determine the predicting factors following radical hysterectomy for stage IB1 carcinoma of the cervix. Materials and Methods: The clinical and histological data of 656 FIGO stage IB1 cervical cancer patients who had radical hysterectomy with bilateral pelvic lymphadenectomy (RHPL) from January 2003 to December 2012 were retrospectively reviewed and were analyzed for their association with a positive vaginal surgical margin. A p-value of < 0.05 was considered significant. Results: Thirty-five patients (5.3%) had positive vaginal surgical margins following RHPL; 24 (3.7%) for intraepithelial lesions and 11 (1.7%) for carcinoma. On multivariate analysis, microscopic vaginal involvement by high-grade squamous intraepithelial lesion and/or carcinoma (adjusted odd ratio (OR) 186.8; 95% confidence interval (CI) 48.5-718.5) and squamous histology (OR 8.7; 95% CI 1.7-44.0), were significantly associated with positive vaginal surgical margin. Conclusions: Microscopic vaginal involvement by HSIL and/or carcinoma are strong predictors for positive vaginal surgical margins for stage IB1 cervical cancer patients undergoing radical hysterectomy. Preoperative 'mapping' colposcopy or other strategies should be considered to ensure optimal vaginal resection. -
Krusun, Srichai;Pesee, Montien;Rasio, Withee;Tangvoraphonkchai, Vorachai;Supaadirek, Chunsri;Thamronganatasakul, Komsan;Supakalin, Narudom;Padoongcharoen, Prawat 2217
Purpose: To evaluate the survival outcome of early stage endometrioid adenocarcinoma of the endometrium with risk factors for locoregional recurrence treated with combined pelvic external beam radiotherapy (EBRT) and vaginal brachytherapy (VBT) after comprehensive surgery. Materials and Methods: Post-operative radiotherapy by pelvic EBRT and VBT for early stage endometrioid endometrial carcinoma resulted in excellent pelvic control with acceptable complications. This study showed no significant relationships between age, stage, histologic grade and LVSI and overall survival rate. Results: The 5-year overall survival rate (OS) of early stage endometrioid type of endometrial carcinoma was 85.7%. Acute toxicity occurred in 38.1% of the patients, all of whom were grade 1 or 2. Total late toxicity developed in 42.9% of study group, in which 36.99% of them were grade 1-2 and 4.76% were grade 3-4. Conclusions: Post-operative radiotherapy by pelvic EBRT and VBT is acceptable for early stage endometrioid endometrial carcinoma, independent of age, stage, histologic grade and LVSI. -
Su, Chong-Yu;Li, Yun-Song;Han, Yi;Zhou, Shi-Jie;Liu, Zhi-Dong 2221
Objective: To explore the relationship between expressions of cell adhesion molecules CD44 v6 and E-cadherin (E-cad) and lymphatic metastasis in non-small cell lung cancer (NSCLC). Materials and Methods: Eightyseven tissue samples obtained from patients with primary NSCLC were collected in our hospital from Dec., 2007 to Dec., 2012, and the expressions of CD44 v6 and E-cad gene proteins in these samples were detected by immunohistochemical method. Results: In the tissue without lymphatic metastasis, the positive expression rate of CD44 v6 was significantly lower, whereas the normal expression rate of E-cad was notably higher than that with lymphatic metastasis (55.6% vs. 78.4%, 47.2% vs. 21.6%), and both differences had statistical significance (P<0.05). Besides, CD44 v6 and E-cad expressions had a significant correlation in the NSCLC tissue with lymphatic metastasis (P<0.05). Conclusions: The positive expression of CD44 v6 and abnormal expression of E-cad may play a very important role in promoting lymphatic metastasis of NSCLC, with synergistic effect. Hence, detection of CD44 v6 and E-cad expressions is conductive to judging the lymphatic metastasis in NSCLC. -
Bektas-Kayhan, Kivanc;Karagoz, Gizem;Kesimli, Mustafa Caner;Karadeniz, Ahmet Nafiz;Meral, Rasim;Altun, Musa;Unur, Meral 2225
Background: Carcinoma of the tongue is the most common intra-oral malignancy in Western countries. Incidence and mortality rates have increased in recent years, and survival has not improved. This study aimed to determine etiologic factors for tongue cancer with age-sex matched case-control data. Materials and Methods: 47 patients with carcinoma of the tongue referred to our oral medicine clinic between years 2005-2006 were analyzed and compared with control group data. The medical records, including family history of cancer, dental trauma, and history of abuse of alcohol and tobacco products was recorded for all subjects. Chi square comparison tests and linear regression analysis were performed using the SPSS program for statistics. Results: Patient and randomly selected control groups each consisted of 30 male and 17 female subjects with mean ages 53.2 (${\pm}12.6$ ) and 52.6 (${\pm}11.5$ ) years respectively. Smoking and alcohol abuse proportions were significantly higher in the patient group (p=0.0001, p<0.0001 respectively). Chronic mechanical trauma was observed in 44.7% of the patients and 17.0% of the control group (p=0.004). Similarly, family history of cancer of any type (for the first degree relatives) was found to be more common in the patient group (p=0.009). On regression analysis, alcohol abuse, family history of cancer, smoking, chronic mechanical traumas appeared as significant etiologic factors (p=0.0001). Conclusions: We believe that field cancerization may become evident in oral and oropharyngeal mucosa with multiple steps of molecular changes starting from the first sign of dysplasia with chronic exposure to etiological factors. Chronic trauma cases need particular attention to search for very early signs of cancer. -
This study investigated how self-rated health and socioeconomic status are associated with behaviour of cancer survivors regarding desire for information. For this association, we compared survivors who did not seek information about cancer with those who did. We examined how sociodemographic, socioeconomic, cancerrelated, and health information factors are associated with self-rated health (SRH) by health information seeking/avoiding behavior in a survey of 502 post-treatment cancer patients. In the information seeking group, all four factors exhibited significant relationships with SRH. SRH values were significantly high for women (p<0.05), non-Hispanic White (p<0.05), and educated (p<0.01) participants, and for those who had high self-efficacy to use health information by themselves (p<0.01). Furthermore, in the information avoiding group, not only were there no significant relationships between socioeconomic status (SES) and SRH, but there were negative associations between their attitude/capacity and the SRH. In terms of communication equity, the promotion of information seeking behavior can be an effective way to reduce health disparities that are caused by social inequalities. Information avoiding behavior, however, does not exhibit a negative contribution toward the relationship between SRH and SES. Information seeking behavior was positively associated with SRH, but avoiding behavior was not negatively associated. We thus need to eliminate communication inequalities using health intervention to support information seeking behavior, while simultaneously providing support for avoiders.
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Zhang, Shuo;Wen, Dong-Qing;Kong, Ya-Lin;Li, Ya-Li;Zhang, Hong-Yi 2239
Objective: To investigate the effects of secondary left-sided portal hypertension (LSPH) on the radical operation rate of patients with pancreatic cancer and systemically evaluate the prognosis of patients with LSPH secondary to pancreatic cancer after radical surgery. Materials and Methods: The data of patients with pancreatic cancer who underwent laparotomy over a 15-year period in Department of Hepatobiliary Surgery of Chinese PLA Air Force General Hospital from Jan. 1, 1997, to Jun. 30, 2012 was retrospectively reviewed. Results: A total of 362 patients with pancreatic cancer after laparotomy were selected, including 73 with LSPH and 289 without LSPH. Thirty-five patients with LSPH (47.9%) and 147 without non-LSPH (50.9%) respectively underwent radical operations. No significant difference was found between these two groups regarding the total resection rate and stratified radical resection rate according to different pathological types and cancer locations. The mean and median survival time of patients after radical operation in LSPH group were$13.9{\pm}1.3$ months and 14.8 months, respectively, while those in non-LSPH group were$22.6{\pm}1.4$ months and 18.4 months, respectively(P<0.05). Conclusions: Radical operations for pancreatic cancer and secondary LSPH are safe and effective. Because high-grade malignancy and poor prognosis are closely associated, the decision for radical surgery should be made more meticulously for the patients with pancreatic cancer. -
Background: Human papillomavirus is a well-established cause of the development of a variety of epithelial lesions in the cervix. However, as yet, incorporation of HPV testing into cervical cancer screening either as an adjunct or stand alone test is limited due to its cost. We therefore here ascertained the presence and type specificity of human papilloma virus (HPV) DNA in routine cervical scrapings. Materials and Methods: Cervical scrapings were collected from women attending clinics for routine Pap smear screening. HPV-DNA was detected by PCR using MY09/11 and GP5+/GP6+ primer sets and genotyping was accomplished by cycle-sequencing. Results: A total of 635 women were recruited into the study with
$mean{\pm}SD$ age of$43{\pm}10.5$ years. Of these 92.6% (588/635) were reported as within normal limits (WNL) on cytology. The presence of HPV infection detected by nested MY/GP+-PCR was 4.4% (28/635). The overall prevalence of high-risk HPV (HR-HPV) in abnormal Pap smears was 53.8% (7/13). HPVs were also seen in 3.1% (18/588) of smears reported as WNL by cytology and 5.9% (2/34) in smears unsatisfactory for evaluation. Conclusions: The overall percentage of HPV positivity in routine cervical screening samples is comparable with abnormal findings in cytology. Conventional Pap smear 'missed' a few samples. Since HPV testing is expensive, our results may provide valuable information for strategising implementation of effective cervical cancer screening in a country with limited resources like Malaysia. If Pap smear coverage could be improved, HPV testing could be used as an adjunct method on cases with ambiguous diagnoses. -
Matsumoto, Kazumasa;Ikeda, Masaomi;Hirayama, Takahiro;Nishi, Morihiro;Fujita, Tetsuo;Hattori, Manabu;Sato, Yuichi;Ohbu, Makoto;Iwam, Masatsugu 2251
Background: The aim of this study was to evaluate 10 years of false positive urine cytology records, along with follow-up histologic and cytologic data, to determine the significance of suspicious urine cytology findings. Materials and Methods: We retrospectively reviewed records of urine samples harvested between January 2002 and December 2012 from voided and catheterized urine from the bladder. Among the 21,283 urine samples obtained during this period, we located 1,090 eligible false positive findings for patients being evaluated for the purpose of confirming urothelial carcinoma (UC). These findings were divided into three categories: atypical, indeterminate, and suspicious of malignancy. Results: Of the 1,090 samples classified as false positive, 444 (40.7%) were categorized as atypical, 367 (33.7%) as indeterminate, and 279 (25.6%) as suspicious of malignancy. Patients with concomitant UC accounted for 105 (23.6%) of the atypical samples, 147 (40.1%) of the indeterminate samples, and 139 (49.8%) of the suspicious of malignancy samples (p<0.0001). The rate of subsequent diagnosis of UC during a 1-year follow-up period after harvesting of a sample with false positive urine cytology initially diagnosed as benign was significantly higher in the suspicious of malignancy category than in the other categories (p<0.001). The total numbers of UCs were 150 (33.8%) for atypical samples, 213 (58.0%) for indeterminate samples, and 199 (71.3%) for samples categorized as suspicious of malignancy. Conclusions: Urine cytology remains the most specific adjunctive method for the surveillance of UC. We demonstrated the clinical value of dividing false positive urine cytology findings into three categories, and our results may help clinicians better manage patients with suspicious findings. -
C1420T Polymorphism of Cytosolic Serine Hydroxymethyltransferase and Risk of Cancer: a Meta-analysisZhong, Shan-Liang;Zhang, Jun;Hu, Qing;Chen, Wei-Xian;Ma, Teng-Fei;Zhao, Jian-Hua 2257
A series of studies have explored the role of cytosolic serine hydroxymethyltransferase (SHMT1) C1420T polymorphism in cancer risk, but their results were conflicting rather than conclusive. To derive a more precise estimation of the association between C1420T and cancer risk, the present meta-analysis of 28 available studies with 15,121 cases and 18,023 controls was conducted. The results revealed that there was no significant association between the polymorphism and cancer risk overall. In stratified analysis by cancer type (breast cancer, gastrointestinal cancer, leukemia, lymphoma, and others), the results showed that 1420T allele was associated with decreased risk in leukemia (CT vs. CC: OR= 0.825, 95% CI =0.704-0.966; and CT+TT vs. CC: OR= 0.838, 95% CI = 0.722-0.973), but the same results were not present for other cancer types. When subgroup analysis was performed by source of control (population-based [PB] and hospital-based [HB]), a borderline inverse association was observed for the HB subgroup (CT vs. CC: OR= 0.917, 95% CI = 0.857-0.982) but not for the PB subgroup. Stratifying by geographic area (America, Asia and Europe), significant inverse association was only found in Asia subgroup (CT vs. CC: OR= 0.674, 95% CI = 0.522-0.870). In summary, the findings suggest that SHMT1 C1420T polymorphism is not associated with overall cancer development, but might decrease cancer susceptibility of Asians as well as reduce leukemia risk. Large well-designed epidemiological studies will be necessary to validate the risk identified in the current meta-analysis. -
Grivas, Nikolaos;Hastazeris, Konstantinos;Kafarakis, Vasileios;Tsimaris, Ioannis;Aspiotis, Spiridon;Stratis, Antonios;Stavropoulos, Nikolaos Efthimios 2263
The aim of the study was to investigate the results of bladder irrigation with Water for Injection (WFI) after transurethral resection of bladder tumours for comparison with those for adjuvant use of BCG. A total of 239 patients (158 with single tumours, group A, and 81 with multiple tumours, group B) received continuous intravesical postoperative irrigation with WFI. Some 128 patients received intravesical irrigation with WFI, followed by weekly instillations of BCG (group C). Recurrence-free rate (RFR) and recurrence-free intervals (RFI) were recorded. RFR for those patients who received only intravesical irrigation with WFI (groups A and B) was 75.8%, 66.2% and 63.2% at the 1st, 2nd and 3rd year of follow up, respectively. Corresponding rates for group C were 61.7%, 55.4% and 49%. Median RFI in group B were 18, 11, 15, 15 and 12 months for Ta, T1, grade 1, grade 2 and grade 3 tumours, respectively. In group C corresponding intervals were 20, 33, 8, 20 and 42 months. BCG improved RFR only in T1 (p=0.014) and grade 3 tumours (p=0.007). In conclusion, postoperative bladder irrigation with WFI could increase RFR during the first and second year of follow up. -
Background: Cancer is one of the most common causes of death in Turkey. Nurses are essential providers of preventive care for patients, especially breast, cervical and colorectal cancer screening as part of routine preventive practice. The aim of this study was to assess knowledge of these cancers among nurses in Karabuk State Hospital. Materials and Methods: This cross-sectional and descriptive study was performed from April 1 to July 30, 2013. The study sample consisted of 226 nurses working in Karabuk State Hospital. Results: Mean age of the nurses was
$32.07{\pm}8.39$ . 62.4% of nurses practiced breast self examination when they remembered it, while 39.8% of them did not take a Pap smear test since they did not think it was necessary. 64.2% of nurses would like to receive information about cancer and screening tests. Majority of them had given true answers to questions on breast, cervical and colorectal cancer. There were significant relationships between cancer knowledge scores and marital status, working experience, and level of education. Conclusions: Nurses possess adequate knowledge about breast cancer but they need more information on cancer risk estimation. Awareness may be raised in nurses by establishing continuing education programs regarding the risk factors, symptoms, protection methods, early diagnosis, and scanning of breast, cervix and colon cancers. -
Jiang, Qian;Yu, You-Cheng;Ding, Xiao-Jun;Luo, Yin;Ruan, Hong 2273
Purpose: The purpose of our study was to explore the molecular mechanisms in the process of oral squamous cells carcinoma (OSCC) development. Method: We downloaded the affymetrix microarray data GSE31853 and identified differentially expressed genes (DEGs) between OSCC and normal tissues. Then Gene Ontology (GO) and Protein-Protein interaction (PPI) networks analysis was conducted to investigate the DEGs at the function level. Results: A total 372 DEGs with logFCI >1 and P value < 0.05 were obtained, including NNMT, BAX, MMP9 and VEGF. The enriched GO terms mainly were associated with the nucleoplasm, response to DNA damage stimuli and DNA repair. PPI network analysis indicated that GMNN and TSPO were significant hub proteins and steroid biosynthesis and synthesis and degradation of ketone bodies were significantly dysregulated pathways. Conclusion: It is concluded that the genes and pathways identified in our work may play critical roles in OSCC development. Our data provides a comprehensive perspective to understand mechanisms underlying OSCC and the significant genes (proteins) and pathways may be targets for therapy in the future. -
Setakornnukul, Jiraporn;Petsuksiri, Janjira;Wanglikitkoon, Sirentra;Warnnissorn, Malee;Thephamongkhol, Kullathorn;Chansilp, Yaowalak;Veerasarn, Vutisiri 2279
Background: To evaluate treatment outcomes of patients with stage I-III endometrial cancer treated with postoperative radiation. Materials and Methods: A retrospective review of 166 endometrial cancer patients, undergoing surgery and postoperative radiotherapy at Siriraj Hospital from 2005-2008 was performed. Pathology was reviewed. Results of treatment were reported with 5-year loco-regional recurrence free survival (LRRFS), 5-year overall survival (OS), patterns of failure and toxicity, and according to stage and risk groups. Results: Median follow up time was 62.8 months. Pathological changes were found in 36.3% of the patients after central reviews, leading to 19% changes in risk groups. Most of the patients (83.7%) received pelvic radiation (PRT) and vaginal brachytherapy (VBT). Five-year LRRFS and OS of all patients were 94.9% and 85.5%, respectively. There was no recurrence or death in low and low-intermediate risk groups. For the high-intermediate risk group, 5-year LRRFS and OS were 96.2% and 90.8%, respectively, and for the high risk group 90.5% and 71%. Late grade 3 and 5 gastrointestinal toxicity was found in 3% and 1.2% of patients, respectively. All of them received PRT 5,000 cGy in 25 fractions. Conclusions: Low and intermediate risk patients had good results with surgery and adjuvant radiation therapy. For high risk patients, postoperative radiation therapy alone appeared to be inadequate as the most common pattern of failure was distant metastasis. -
Sadighi, Sanambar;Amanpour, Saeid;Behrouzi, Bita;Khorgami, Zhinoos;Muhammadnejad, Samad 2287
Background: In the past few years, a considerable number of preclinical studies have been proposed metformin as a potential anticancer agent, but some of these studies suffer from a number of methodological limitations such as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applying suprapharmacological levels of the drug. These objections have limited the translation of published preclinical data to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin on different molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemic conditions in vitro. Materials and Methods: Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTTbased cytotoxicity assays were also performed with metformin alone or in combination with paclitaxel. Results: Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell lines in the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the antineoplastic properties of paclitaxel was apparent under the tested conditions. Conclusions: Metformin is probably unable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasma concentration of metformin in the clinical setting for assessment of anticancer effects in normoglycemic patients. -
Guo, Yu;Liao, Ya-Ping;Zhang, Ding;Xu, Li-Sha;Li, Na;Guan, Wei-Jun;Liu, Chang-Qing 2291
Although nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis and expression has been observed in some types of human cancer and stem cells, the molecular mechanisms involved in mediation of cell proliferation and cell cycling remains largely elusive. The aim of the present study was to evaluate NS as a potential target for gene therapy of human breast carcinoma by investigating NS gene expression and its effects on SKBR-3 cell proliferation and apoptosis. NS mRNA and protein were both found to be highly expressed in all detected cancer cell lines. The apoptotic rate of the pcDNA3.1-NS-Silencer group ($12.1-15.4{\pm}3.8%$ ) was significantly higher than those of pcDNA3.1-NS ($7.2-12.0{\pm}1.7%$ ) and non-transfection groups ($4.1-6.5{\pm}1.8%$ , P<0.01). MTT assays showed the knockdown of NS expression reduced the proliferation rate of SKBR-3 cells significantly. Matrigel invasion and wound healing assays indicated that the number of invading cells was significantly decreased in the pcDNA3.1-NS-siRNA group (P<0.01), but there were no significant difference between non-transfected and over-expression groups (P>0.05). Moreover, RNAi-mediated NS down-regulation induced SKBR-3 cell G1 phase arrest, inhibited cell proliferation, and promoted p53 pathway-mediated cell apoptosis in SKBR-3 cells. NS might thus be an important regulator in the G2/M check point of cell cycle, blocking SKBR-3 cell progression through the G1/S phase. On the whole, these results suggest NS might be a tumor suppressor and important therapeutic target in human cancers. -
Objective: To evaluate early treatment for extranodal natural killer/T cell lymphoma (ENK/TCL) in China and provide reference for clinical treatment of these patients. Methods: Computer-based retrieval was performed in PubMed, CNKI, CBM, VIP and WanFang Data to search for randomized controlled trials (RCTs) of treatment for early ENK/TCL, and a meta-analysis was conducted with RevMan 5.0 software. Results: A total of 11 RCTs, including 871 patients, were selected, of which the first radiotherapy had a higher complete response (CR) than the first chemotherapy [OR=14.16, 95%CI (8.68, 23.10), P<0.00001] and CR was not different between combined treatment group and radiotherapy group [OR=1.86, 95%CI (0.47, 3.58), P=0.61], but long-term survival rate was higher with combined treatment[OR=1.88, 95%CI (1.09, 3.19), P=0.02]. No difference in survival rate was observed between radio-chemotherapy and chemo-radiotherapy groups [OR=1.11, 95%CI (0.73, 1.69), P=0.63]. Conclusions: Radiotherapy is of great significance in the treatment of early ENK/TCL, but combined therapy could further enhance long-term survival rate of patients. This conclusion still requires further confirmation using RCTs with high quality and large sample size.
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Hashmi, Atif Ali;Ali, Rabia;Hussain, Zubaida Fida;Faridi, Naveen 2303
Background: Renal cancer is a serious public health problem which may be under reported and registered in our setup, since the Karachi cancer registry documented only 43 cases out of 4,268 incident cancer cases over 3 year duration. Therefore we aimed to determine the clinicopathologic characteristics of adult renal tumors in our setup. Materials and Methods: The study was conducted in histopathology department, Liaquat National Hospital and included total of 68 cases of adult renal tumors over 4 years. Detailed histopathologic characteristics of tumors were analyzed. Results: Mean age of patients was 56.4 (18-84) years. Renal cell carcinoma (RCC) was the most common cell type (78%) cases; followed by transitional/urothelial carcinoma (12.5%), leiomyosarcoma (4.7%), oncocytoma (1.6%), squamous cell carcinoma (1.6%) and high grade pleomorphic undifferentiated sarcoma (1.6%). Among 50 RCC cases; 62% were conventional/clear cell RCC (CCRCC) type followed by papillary RCC(PRCC), 24%; chromophobe RCC(CRCC), 6% and sarcomatoid RCC(SRCC), 8%. Mean tumor size for RCC was 7.2 cm. Most RCCs were intermediate to high grade (60% and 40% respectively). Capsular invasion, renal sinus invasion, adrenal gland involvement and renal vein invasion was seen in 40%, 18%, 2% and 10% of cases respectively. Conclusions: We found that RCC presents at an earlier age in our setup compared to Western populations. Tumor size was significantly larger and most of the tumors were of intermediate to high grade. This reflects late presentation of patients after disease progression which necessitates effective measures to be taken in primary care setup to diagnose this disease at an early stage. -
Jiang, Yu-Zhang;Li, Qian-Hui;Zhao, Jian-Qiang;Lv, Jun-Ji 2309
Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer and is characterized by a poor prognosis. Determining gene changes in ESCCs should improve understanding of putative risk factors and provide potential targets for therapy. We sequenced about 55 million pair-end reads from a pair of adjacent normal and ESCC samples to identify the gene expression level and gene fusion. Sanger sequencing was used to verify the result. About 17 thousand genes were expressed in the tissues, of which approximately 2400 demonstrated significant differences between tumor and adjacent non tumor tissue. GO and KEGG pathway analysis revealed that many of these genes were associated with cellular adherence and movement, simulation responses and immune responses. Notably we identified and validated one fusion gene, HLA-E and HLA-B, located 1 MB apart. We also identified thousands of remarkably expressed transcripts. In conclusion, a novel fusion gene HLA-E and HLA-B was identified in ESCC via whole transcriptome sequencing, which would be a biomarker for ESCC diagnosis and target for therapy, shedding new light for better understanding of ESCC tumorigenesis. -
Chen, Hui-Min;Zhang, Ding-Guo;Wu, Jin-Xiz;Pei, Dong-Sheng;Zheng, Jun-Nian 2313
Peroxisome proliferator-activated receptor gamma (PPAR-${\gamma}$ ), a ligand-dependent nuclear transcription factor, has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. In this study, we investigated the effect of PPAR-${\gamma}$ on aspects of the cervical cancer malignant phenotype, such as cell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysis consistently showed that treatment with troglitazone (TGZ, a PPAR-${\gamma}$ agonist) led to dose-dependent inhibition of cervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-${\gamma}$ antagonist) had no effect on Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 and Mdm2 to explain the underlying mechanism of PPAR-${\gamma}$ on cellular apoptosis. Our work, finally, demonstrated the existence of the TGZ-PPAR-${\gamma}$ -p53 signaling pathway to be a critical regulator of cell apoptosis. These results suggested that PPAR-${\gamma}$ may be a potential therapeutic target for cervical cancer. -
Coskunpinar, Ender;Canbay, Emel;Oltulu, Yasemin Musteri;Tiryakioglu, Necip Ozan;Bugra, Dursun 2319
Our aim was to determine GSTT1 expression levels in left colon tumors and paired normal tissue in order to identify specific alterations in GSTT1 mRNA levels. Alterations in GSTT1 expression in twenty-four left-sided colon tumors and paired cancer free tissue were determined by qRT-PCR. Significant fold changes were determined with t-test. When compared with cancer free tissue, left colon cancers showed a significant decrease in GSTT1 expression. However, GSTT1 mRNA levels among different grades increased gradually in correlation with tumor grade. Our results suggest that downregulation of GSTT1 in left-sided colon cancers is an early event and is reversed with cancer progression, probably due to cellular defense mechanisms as a response to changes in the microenvironment. -
Liu, Meng;Cui, Lian-Hua;Ma, Ai-Guo;Li, Na;Piao, Jin-Mei 2323
Background: Epidemiological findings are controversial relating to the relationship between dietary folate intake and the risk of breast cancer. We therefore conducted a meta-analysis of prospective cohort studies to clarify this association. Materials and Methods: PUBMED, EMBASE, and MEDLINE databases were searched for all relevant literature published in English from January 1, 1966 to August 2013. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using a fixed or random effects model. Results: Dietary folate intake was not significantly associated with the risk of breast cancer. The combined RR with 95%CI for the highest vs. lowest category dietary intake of folate [fifteen studies; 1,836,566 participants and 24,083 patients with breast cancer] was 0.98 (0.90-1.05). Among subgroup analysis by menstrual status, hormonal status and the consumption of alcohol, methionine and vitamin B12, no significant association was observed for the dietary intake of folate and the risk of breast cancer. Dose-response analysis showed that a 220${\mu}g/day$ increment in dietary folate intake was not associated with the risk of breast cancer. Conclusions: Our findings indicate that dietary folate intake has no significant effect on the risk of breast cancer. -
Li, Pei-Min;Li, Yu-Liang;Liu, Bin;Wang, Wu-Jie;Wang, Yong-Zheng;Li, Zheng 2329
Curcumin can inhibit proliferation of liver cancer cells by inducing apoptosis, but the specific signaling pathways involved are not completely clear. Here, we report that curcumin inhibited proliferation of MHCC97H liver cancer cells by induction of apoptosis in a concentration dependent manner via stimulating intracellular reactive oxygen species (ROS) generation. Also, we showed that increased intracellular ROS formation activated the TLR-4/MyD-88 signaling pathway, resulting in activation of caspase-8 and caspase-3, which eventually led to apoptosis in MHCC97H cells. These results showed that as an prooxidant, curcumin exerts anti-cancer effects by inducing apoptosis via the TLR-4/MyD-88 signaling pathway. -
Yadav, Deepak;Anwar, Mohammad Faiyaz;Garg, Veena;Kardam, Hemant;Beg, Mohd Nadeem;Suri, Suruchi;Gaur, Sikha;Asif, Mohd 2335
Paclitaxel is hydrophobic in nature and is recognized as a highly toxic anticancer drug, showing adverse effects in normal body sites. In this study, we developed a polymeric nano drug carrier for safe delivery of the paclitaxel to the cancer that releases the drug in a sustained manner and reduces side effects. N-isopropylacrylamide/vinyl pyrrolidone (NIPAAm/VP) nanoparticles were synthesized by radical polymerization. Physicochemical characterization of the polymeric nanoparticles was conducted using dynamic light scattering, transmission electron microscopy, scanning electron microscopy and nuclear magnetic resonance, which confirmedpolymerization of formulated nanoparticles. Drug release was assessed using a spectrophotometer and cell viability assays were carried out on the MCF-7 breast cancer and B16F0 skin cancer cell lines. NIPAAm/VP nanoparticles demonstrated a size distribution in the 65-108 nm range and surface charge measured -15.4 mV. SEM showed the nanoparticles to be spherical in shape with a slow drug release of ~70% in PBS at$38^{\circ}C$ over 96 h. Drug loaded nanoparticles were associated with increased viability of MCF-7 and B16F0 cells in comparison to free paclitaxel. Nano loaded paclitaxel shows high therapeutic efficiency by sustained release action for the longer period of time, i increasing its efficacy and biocompatibility for human cancer therapy. Therefore, paclitaxel loaded (NIPAAm/VP) nanoparticles may provide opportunities to expand delivery of the drug for clinical selection. -
Background: p53 protein expression has been detected immunohistochemically in papillary thyroid carcinoma(PTC). We investigated the relations between its expression and clinicopathologic features and its significance as a diagnostic marker. Materials and Methods: We compared and evaluated 93 patients in whom thyroidectomy with lymph node dissection had been performed to treat PTC for clinicopathologic significance and 102 patients with 23 papillary thyroid overt carcinomas (POC), 57 papillary thyroid microcarcinomas(PMC), 5 follicular adenomas (FA), 5 Hashimoto's thyroiditis (HT) and 12 nodular hyperplasias (NH) for significance as a diagnostic marker. Expression of p53 protein was evaluated immunohistochemically in sections of paraffinembedded tissue. Results: Statistical analysis showed significantly different expression of p53 in PTC versus other benign thyroid lesions (BTL).The diagnostic sensitivity and specificity were 85.0% and 72.7%, respectively. Overexpression of p53 protein was observed in 44 of the 93 PTC cases (47.3%), but no significant correlation between p53 protein overexpression and clinicopathologic features (age, size, multiplicity, lymph node metastasis, extrathyroidal extension and vascular invasion) was noted. Conclusions: p53 is valuable to distinguish PTC from other BTL, but there is no correlation between p53 protein overexpression and clinicopathologic features.
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Wu, Bing-Li;Zou, Hai-Ying;Lv, Guo-Qing;Du, Ze-Peng;Wu, Jian-Yi;Zhang, Pi-Xian;Xu, Li-Yan;Li, En-Min 2345
Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase (LOX) family, is a copper-dependent enzyme that catalyzes oxidative deamination of lysine residues on protein substrates. LOXL2 was found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous research. We later identified a LOXL2 splicing variant LOXL2-delta72 and we overexpressed LOXL2-delta72 and its wild type counterpart in ESCC cells following microarray analyses. First, the differentially expressed genes (DEGs) of LOXL2 and LOXL2-delta72 compared to empty plasmid were applied to generate protein-protein interaction (PPI) sub-networks. Comparison of these two sub-networks showed hundreds of different proteins. To reveal the potential specific roles of LOXL2- delta72 compared to its wild type, the DEGs of LOXL2-delta72 vs LOXL2 were also applied to construct a PPI sub-network which was annotated by Gene Ontology. The functional annotation map indicated the third PPI sub-network involved hundreds of GO terms, such as "cell cycle arrest", "G1/S transition of mitotic cell cycle", "interphase", "cell-matrix adhesion" and "cell-substrate adhesion", as well as significant "immunity" related terms, such as "innate immune response", "regulation of defense response" and "Toll signaling pathway". These results provide important clues for experimental identification of the specific biological roles and molecular mechanisms of LOXL2-delta72. This study also provided a work flow to test the different roles of a splicing variant with high-throughput data. -
Zhang, Yong-Chun;Jiang, Gang;Gao, Han;Liu, Hua-Min;Liang, Jun 2353
Purpose: We aimed to detect the expression of HIF-1${\alpha}$ , VEGF, HPSE-1 and CD31 in SKOV3 xenografts in nude mice treated with different doses of ionizing radiation, trying to explore the possible mechanism of hypoxia and radioresistance. Methods: Nude mice bearing SKOV3 xenografts were randomly divided into 4 groups: Group A (control group, no ionizing radiation), Group B (treated with low dose of ionizing radiation: 50cGy), Group C (treated with high dose of ionizing radiation: 300cGy), Group D ( combined ionizing radiation, treated with ionizing radiation from low dose to high dose : 50cGy first and 300cGy after 6h interval). The mRNA levels of HIF-1 and VEGF in each group were detected by real time polymerase chain reaction, while HPSE-1 expression was measured by ELISA. The microvessel density (MVD) and hypoxic cells were determined through immunohistochemical (IHC) staining of CD31 and HIF-1a. Results: Significant differences of HIF-1${\alpha}$ mRNA level could be found among the 4 groups (F=74.164, P<0.001): Group C>Group A>Group D> Group B. The mRNA level of VEGF in Group C was significantly higher than in the other three groups (t=-5.267, P=0.000), while no significant difference was observed among Group A, B and D (t=1.528, 1.588; P=0.205, 0.222). In addition, the MVD was shown to be the highest in Group C (t=6.253, P=0.000), whereas the HPSE-1 level in Group A was lower than in Group B (t=14.066, P=0.000) and higher than in Group C (t=-21.919, P=0.000), and similar with Group D (t=-2.066, P=0.058). Through IHC staining of HIF-1a, the expression of hypoxic cells in Group A was (++), Group B was (+), Group C was (+++) and Group D was (+). Conclusion: Ionizing radiation with lowerdoses might improve tumor hypoxia through inhibiting the expression of HIF-1 and HPSE-1, whereas higherdoses worsen tumor hypoxic conditions by up-regulating HIF-1${\alpha}$ , HPSE-1, VEGF and CD31 levels. A protocol of low-dose ionizing radiation followed by a high-dose irradiation might at least partly improve tumor hypoxia and enhance radiosensitivity. -
Background: To investigate the effects of double radiofrequency hyperthermia on Th1/Th2 cells in esophageal cancer patients treated with radiotherapy. Materials and Methods: 22 patients with esophageal cancer were divided into a radiotherapy group (10 cases) and a combined group (double radiofrequency hyperthermia combined with radiotherapy group, 12 cases). Both groups received conventional radiotherapy using a cobalt-60 therapy apparatus (TD60-66Gy/30-33F). Patients in the combined group also underwent double radiofrequency hyperthermia (2F/W, 8-10F). Before and after treatment, Th1, Th2, Tc1 and Tc2 cells in peripheral blood were determined with flow cytometry. Results: In the radiotherapy group, Th1 cell contents before and after radiotherapy were
$17.5{\pm}5.26%$ and$9.69{\pm}4.86%$ , respectively, with a significant difference (p<0.01). The Th1/Th2 ratio was significantly decreased from$28.2{\pm}14.3$ to$16.5{\pm}10.4 $ (p<0.01). In the combined group, Th1 cell content before radiotherapy was$15.9{\pm}8.18%$ , and it increased to$18.6{\pm}8.84$ after radiotherapy (p>0.05), the Th1/Th2 ratio decreasing from$38.4{\pm}36.3$ to$28.1{\pm}24.0$ (p>0.05). Changes in Th2, Tc1 and Tc2 cell levels were not significant in the two groups before and after therapy (p>0.05). Conclusions: Double radiofrequency hyperthermia can promote the conversion from Th2 to Th1 cells, and regulate the balance of Th1/Th2 cells. -
Hu, Wei-Guo;Hu, Jia-Jia;Cai, Wei;Zheng, Min-Hua;Zang, Lu;Wang, Zheng-Ting;Zhu, Zheng-Gang 2363
The association between the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. Although our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between gastric cancer patients and controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated a significantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20-1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84), dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratified analysis by study design demonstrated stronger associations in population-based than in hospital-based studies. And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 gene C609T polymorphism increases the risk for gastric cancer, especially in Asian populations. -
Shen, Chen-Tian;Qiu, Zhong-Ling;Luo, Quan-Yong 2369
Background and Aim: Selumetinib is a promising and interesting targeted therapy agent as it may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer. We conduct this metaanalysis to compare the efficacy and safety of selumetinib with current therapies in patients with advanced cancer. Methods: An electronic search was conducted using PubMed/ Medicine, EMBASE and Cochrane library databases. Statistical analyses were carried out using either random-effects or fixed-effects models according to the heterogeneity of eligible studies. Results: Six eligible trials involved 601 patients were identified. Compared with current therapies, treatment schedules with selumetinib did not improve progression free survival (hazard ratio, 0.91; 95%CI 0.70-1.17, P= 0.448), but did identify better clinical benefits (odds ratio, 1.24; 95%CI 0.69-2.24, P = 0.472) and less disease progression (hazard ratio, 0.72; 95%CI 0.51-1.00, P = 0.052) though its impact was not statistically significant. Sub-group analysis resulted in significantly improved progression free survival (hazard ratio, 0.61; 95%CI 0.49-0.57, P = 0.00), clinical benefits (odds ratio, 3.04; 95%CI 1.60-5.77, P = 0.001) and reduced disease progression (hazard ratio, 0.35; 95%CI 0.18-0.67, P = 0.001) in patients administrated selumetinib. Dermatitis acneiform (risk ratio, 9.775; 95%CI 3.143-30.395, P = 0.00) and peripheral edema (risk ratio, 2.371; 95%CI 1.690-3.327, P = 0.00) are the most frequently observed adverse effects associated with selumetinib. Conclusions: Compared with current chemotherapy, selumetinib has modest clinical activity as monotherapy in patients with advanced cancer, but combinations of selumetinib with cytotoxic agents in patients with BRAF or KRAS mutations hold great promise for cancer treatment. Dermatitis acneiform and peripheral edema are the most frequently observed adverse effects in patients with selumetinib. -
Vemuri, Ravi Chandra;Jarecha, Rudresh;Hwi, Kim Kah;Gundamaraju, Rohit;MaruthiKanth, Aripaka;Kulkarni, AravindRao;Reddy, Sundeep 2375
Cancer, like any disease, is a pathologic biological process. Drugs are designed to interfere with the pathologic process and should therefore also be validated using a functional screening method directed at these processes. Screening for cancers at an appropriate time and also evaluating results is also very important. Volumetric measurement helps in better screening and evaluation of tumors. Volumetry is a process of quantification of the tumors by identification (pre-cancerous or target lesion) and measurement. Volumetric image analysis allows an accurate, precise, sensitive, and medically valuable assessment of tumor response. It also helps in identifying possible outcomes such disease progression (PD) or complete response as per Response Evaluation Criteria in Solid Tumors (RECIST). -
Sehitoglu, Muserref Hilal;Farooqi, Ammad Ahmad;Qureshi, Muhammad Zahid;Butt, Ghazala;Aras, Aliye 2379
It is becoming progressively more understandable that phytochemicals derived from edible plants have shown potential in modelling their interactions with their target proteins. Rapidly accumulating in-vitro and in- vivo evidence indicates that anthocyanins have anticancer activity in rodent models of cancer. More intriguingly, evaluation of bilberry anthocyanins as chemopreventive agents in twenty-five colorectal cancer patients has opened new window of opportunity in translating the findings from laboratory to clinic. Confluence of information suggests that anthocyanins treated cancer cells reveal up-regulation of tumor suppressor genes. There is a successive increase in the research-work in nutrigenomics and evidence has started to shed light on intracellular-signaling cascades as common molecular targets for anthocyanins. In this review we bring to l imelight how anthocyanins induced apoptosis in cancer cells via activation of extrinsic and intrinsic pathways. -
Oberoi, Sukhvinder Singh;Sharma, Gaurav;Nagpal, Archana;Oberoi, Avneet 2383
Tobacco use is described as the single most preventable cause of morbidity and mortality globally, with the World Bank predicting over 450 million tobacco-related deaths in the next fifty years. In India, the proportion of all deaths that can be attributed to tobacco use is expected to rise from 1.4% in 1990 to 13.3% in 2020 of which smoking alone will cause about 930,000 adult deaths by 2010. Many studies have shown that counseling from a health professional is an effective method of helping patients quit the tobacco habit. Tobacco cessation needs to be urgently expanded by training health professionals in providing routine clinical interventions, increasing availability and subsidies of pharmacotherapy, developing wide-reaching strategies such as quitlines, and costeffective strategies, including group interventions. The WHO Framework Convention on Tobacco Control (FCTC) emphasizes the vital contribution of participation of health professional bodies, as well as training and healthcare institutions in tobacco control efforts. Dentists can play an important role in helping patients quit using tobacco. One of the key strategies to reduce tobacco-related morbidity and mortality is to encourage the involvement of health professionals in tobacco-use prevention and cessation counselling. The dental office is an ideal setting for tobacco cessation services since preventive treatment services, oral screening, and patient education have always been a large part of the dental practice. -