Asian Pacific Journal of Cancer Prevention
Asian Pacific Organization for Cancer Prevention (아시아태평양암예방학회)
Health Sciences > Development of Pharmaceutical
The Asian Pacific Journal of Cancer Prevention is a monthly electronic journal publishing papers in all areas of cancer control. Its is indexed on PubMed (Impact factor for 2014 : 2.514) and the scope is wide-ranging: including descriptive, analytical and molecular epidemiology; experimental and clinical histopathology/biology of preneoplasias and early neoplasias; assessment of risk and beneficial factors; experimental and clinical trials of primary preventive measures/agents; screening approaches and secondary prevention; clinical epidemiology; and all aspects of cancer prevention education. All of the papers published are freely available as pdf files downloadable from www.apjcpcontrol.org, directly or through PubMed, or obtainable from the first authors. The APJCP is financially supported by the UICC Asian Regional Office and the National Cancer Center of Korea, where the Editorial Office is housed.
KSCI
Volume 17 Issue sup3
Anti-Oxidant, Pro-Oxidant and Anti-Inflammatory Effects of Unpolished Rice Relevant to Colorectal Cancer
Suwannalert, Prasit;Payuhakrit, Witchuda;Koomsang, Thidarat 5047
https://doi.org/10.22034/APJCP.2016.17.12.5047 KSCI
Colorectal cancer (CRC) is a major worldwide health problem owing to its high prevalence and mortality rates. Carcinogenesis in the colon is a multistage and multifactorial process. An imbalance between free radical exposure and anti-oxidant defense systems may leads to oxidative stress and attack of macromolecules which can alter signal transduction pathways and gene expression. Consequently, oxidative damage can lead to cellular dysfunction and contribute to pathophysiological processes in a variety of diseases including CRC. One factor tightly associated with CRC is chronic inflammation, which can be present from the earliest stage of tumor onset. Unpolished rice is an attractive chemoprevention in CRC due to their anti-oxidant and anti-inflammatory activities. The aim of this paper is to review evidence linking oxidative stress and inflammation to CRC and to provide essential background information for understanding future research on oxidative stress and inflammation on CRC. Mechanisms of action of unpolished rice in CRC carcinogenesis are also discussed.
Intra-Operative Frozen Sections: Experience at A Tertiary Care Centre
Preeti, Agarwal;Sameer, Gupta;Kulranjan, Singh;Abhinav, Sonkar Arun;Preeti, Rani;Sunita, Yadav;Mati, Goel Madhu 5057
The present study was conducted to assess error rates with diagnosis using intra-operative frozen sections, and to indicate ways to increase overall performance. Over a period of two years, 227 cases were biopsied intra-operatively. Errors were observed in 14 cases. Four of these were sampling errors, one by a pathologist and three by surgeons. In seven cases incorrect interpretations were made. Epithelial dysplasia was observed on definitive histology in two cases which was not reported intra-operatively. One case was of ectopic thyroid. In cases of oral cancer where sentinel lymph nodes were sampled, immunohistochemistry for cytokeratin was performed to facilitate identification of micrometastasis. Only single case displayed tumor deposits which was not evident morphologically. Resection margins were reported in seventy eight cases. Some 18% (14/50) benefited from revision of margins; overall sensitivity of intra-operative frozen sections for marginal status was 71.4%, with a specificity of 90.3%. Overall sensitivity was 75% and specificity was 97.5%. Careful observation, pathologist experience and knowledge of limitations help in improving the overall diagnostic outcome.
Health-Related Quality of Life among Breast Cancer Patients and Influencing Factors in Morocco
El Fakir, Samira;El Rhazi, Karima;Zidouh, Ahmed;Bennani, Maria;Benider, Abdelatif;Errihani, Hassan;Mellass, Nawfel;Bekkali, Rachid;Nejjari, Chakib 5063
Background: Breast cancer is the most common cancer among women in most countries of the world. It is ranked first in females in Morocco (accounting for 33.4% of the total cancer burden) and more than 60% of cases are diagnosed at stage III or IV. During the last decade, health-related quality of life (HRQOL) has become an important aspect of breast cancer treatment. The objective of this study was to describe self-reported HRQOL in patients with breast cancer and to investigate its associations with sociodemographic and clinical variables. Methods: A prospective study was carried out in the main oncology centers in Morocco. Quality of life was measured using the Moroccan Arabic versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C 30 (EORTC QLQ C30) and the Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23). Statistical analyses were performed using descriptive statistics and multivariate analyses. Results: A total of 1463 subjects were included in the study, with a mean age of 55.6 (SD. 11.2) years, 70% being married. The majority had stage II (45.9%) and a few cases stage IV (12.9%) lesions. The participants' global health mean score was 68.5 and in "functional scales", social functioning scored the highest (Mean 86.2 (SD=22.7)). The most distressing symptom on the symptom scale was financial difficulties (Mean 63.2 (SD=38.2)). Using the disease specific tool, it was found that future perspective scored the lowest (Mean 40.5 (SD=37.3)). On the symptom scale, arm symptoms scored the highest (Mean 23.6 (SD=21.6)). Significant mean differences were noted for many functional and symptom scales. Conclusion: Our results emphasized that the general HRQOL for our study population is lower than for corresponding populations in other countries. This study provided baseline information on the quality of life for a large sample of Moroccan women diagnosed with breast cancer.
Red Seaweed (Hypnea Bryodies and Melanothamnus Somalensis) Extracts Counteracting Azoxymethane-Induced Hepatotoxicity in Rats
Waly, Mostafa Ibrahim;Al Alawi, Ahmed Ali;Al Marhoobi, Insaaf Mohammad;Rahman, Mohammad Shafiur 5071
Background: Azoxymethane (AOM) is a well-known colon cancer-inducing agent in experimental animals via mechanisms that include oxidative stress in rat colon and liver tissue. Few studies have investigated AOM-induced oxidative stress in rat liver tissue. Red seaweeds of the genera Hypnea Bryodies and Melanothamnus Somalensis are rich in polyphenolic compounds that may suppress cancer through antioxidant properties, yet limited research has been carried out to investigate their anti-carcinogenic and antioxidant influence against AOM-induced oxidative stress in rat liver. Objective: This study aims to determine protective effects of red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts against AOM-induced hepatotoxicity and oxidative stress. Materials and Methods: Sprague-Dawley rats received intraperitoneal injections of AOM, 15 mg/kg body weight, once a week for two consecutive weeks and then orally administered red seaweed (100 mg/kg body-weight) extracts for sixteen weeks. At the end of the experiment all animals were overnight fasted then sacrificed and blood and liver tissues were collected. Results: AOM treatment significantly decreased serum liver markers and induced hepatic oxidative stress as evidenced by increased liver tissue homogenate levels of nitric oxide and malondialdehyde, decreased total antioxidant capacity and glutathione, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and superoxide dismutase). Both red seaweed extracts abolished the AOM-associated oxidative stress and protected against liver injury as evidenced by increased serum levels of liver function markers. In addition, histological findings confirmed protective effects of the two red seaweed extracts against AOM-induced liver injury. Conclusion: Our findings indicate that red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts counteracted oxidative stress-induced hepatotoxicity in a rat model of colon cancer.
Factors Associated with Tobacco Use in Students Attending Local Government Schools in Mumbai, India
Chatterjee, Nilesh;Todankar, Priyamvada;Mandal, Gauri;Gupte, Himanshu;Thawal, Vaibhav;Bhutia, Tshering;Choudhuri, Leni 5075
Purpose: Factors associated with ever-use and differences between ever-users and non-users of tobacco among adolescent school students from low income families in Mumbai were assessed. Materials and Methods: A self-administered questionnaire, completed by 1918 students from grades 7, 8 and 9 in 12 schools managed by the city municipal corporation in July 2015, gathered data on socio-demographic characteristics, tobacco use and tobacco-related knowledge, attitudes and beliefs. Results: Although only 1% of respondents thought tobacco was cool, nearly 35% were unaware of associations between tobacco use and health problems. Male students were almost twice as likely (OR=2.5, P <= 0.05) to have ever used tobacco compared to females and Supari (areca nut) users were eight times more likely (OR=8.99, P < 0.001) than Supari non -users. Tobacco-users were more likely to agree with statements: 'People who use tobacco have more friends' (OR=2.8, P = 0.004), 'Smoking relieves stress' (OR=5.6, P = 0.002) and 'It is possible to purchase any tobacco product within 100 yards of school' (OR=10.8, P < 0.001). Conclusion: This study highlights the gains made by tobacco prevention campaigns in that almost all students did not consider tobacco as cool or a stress reliever. However, they still need education about health consequences of tobacco-use. In addition, Supari use has to be addressed in school-based tobacco prevention and cessation initiatives. Furthermore, programs must also address perceptions and norms related to peers and tobacco use and ensure active implementation of existing laws. Such integrated measures will help ensure tobacco-free spaces around schools.
Clinico-Pathologic Subtypes of Breast Cancer Primary Tumors Are Related to Prognosis after Recurrence
Sanchez, Cesar;Camus, Mauricio;Medina, Lidia;Oddo, David;Artigas, Rocio;Sepulveda, Alejandra Perez;Domainguez, Francisco;Razmilic, Dravna;Navarro, Maria Elena;Galindo, Hector;Acevedo, Francisco 5081
Background: Pathological factors, based mainly on immunohistochemistry (IHC) and histological differentiation, are mostly used to differentiate breast cancer (BC) subtypes. Our present aim was to describe the characteristics and survival of a relapsing BC patient cohort based on clinico-pathologic subtypes determined for the primary tumors. Methods: We used a clinico- pathological definition of BC subtypes based on histological grade (HG), estrogen receptor (ER), progesterone receptor (PgR),and epidermal growth factor receptor type 2 (HER2) expression assessed by IHC. We determined variables associated with loco-regional recurrence (LRR), second primaries (SP), systemic recurrence (SR) and post-recurrence survival (PRS). Results: Out of 1,702 patients, 240 (14%) had an event defined as recurrence. Those with recurrent disease were significantly younger than those without,and were initially diagnosed at more advanced stages, with larger tumors, greater lymph nodal involvement and higher HG. With a median follow up of 61 months (1-250), 4.6% of patients without recurrence and 56.6% of patients with an event defined as recurrence had died. The median PRS for the LRR group was 77 months; 75 months for those who developed a SP and 22 months for patients with an SR (p <0.0001). In SR cases, the median PRS was shorter for ER- tumors than for ER+ tumors (15 vs. 26 months, respectively; p = 0.0019, HR 0.44; CI: 0.25-0.44). Conclusions: Subtype, defined through classic histopathologic parameters determined for primary tumors, was found to eb related to type of recurrence and also to prognosis after relapse.
New Insights into mTOR Signal Pathways in Ovarian-Related Diseases: Polycystic Ovary Syndrome and Ovarian Cancer
Liu, Ai Ling;Liao, Hong Qing;Li, Zhi Liang;Liu, Jun;Zhou, Cui Lan;Guo, Zi Fen;Xie, Hong Yan;Peng, Cui Ying 5087
mTOR, the mammalian target of rapamycin, is a conserved serine/threonine kinase which belongs to the phosphatidyl-linositol kinase-related kinase (PIKK) family. It has two complexes called mTORC1 and mTORC2. It is well established that mTOR plays important roles in cell growth, proliferation and differentiation. Over-activation of the mTOR pathway is considered to have a relationship with the development of many types of diseases, including polycystic ovary syndrome (PCOS) and ovarian cancer (OC). mTOR pathway inhibitors, such as rapamycin and its derivatives, can directly or indirectly treat or relieve the symptoms of patients suffering from PCOS or OC. Moreover, mTOR inhibitors in combination with other chemical-molecular agents may have extraordinary efficacy. This paper will discuss links between mTOR signaling and PCOS and OC, and explore the mechanisms of mTOR inhibitors in treating these two diseases, with conclusions regarding the most effective therapeutic approaches.
Multiparity and Breast Cancer Risk Factor among Women in Burkina Faso
Zoure, Abdou Azaque;Bambara, Aboubacar Hierrhum;Sawadogo, Alexis Yobi;Ouattara, Abdoul Karim;Ouedraogo, Marie;Traore, Si Simon;Bakri, Youssef;Simpore, Jacques 5095
The relative lack of information on breast cancer etiology in Burkina Faso led us to undertake the present work to highlight risk factors. This prospective study was conducted using a questionnaire between January 2015 and February 2016 on women admitted to Yalgado OUEDRAOGO hospital, for consultation or supervision. The characteristics of multiparous breast cancer patients (n = 44) were compared with their non-multiparous counterparts (n = 36). The study found that increased risk of breast cancer among non-multiparous cases was related to body mass index (BMI) (p <0.001), age at menopause (p <0.004) and use of oral contraception (p <0.021) while abortion (p <0.002) was a risk factor among multiparous cases. These results suggest that even if multiparity is associated with a decreased risk in some women, avoidance of abortion during reproductive life should be recommended. The results provide preliminary information, which now need to be supplemented by survey of a larger sample in the national territory.
A New Inflammatory Prognostic Index, Based on C-reactive Protein, the Neutrophil to Lymphocyte Ratio and Serum Albumin is Useful for Predicting Prognosis in Non-Small Cell Lung Cancer Cases
Dirican, Nigar;Dirican, Ahmet;Anar, Ceyda;Atalay, Sule;Ozturk, Onder;Bircan, Ahmet;Akkaya, Ahmet;Cakir, Munire 5101
Purpose: We aimed to establish an inflammatory prognostic index (IPI) in early and advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze its predictive value for NSCLC survival. Materials and Methods: A retrospective review of 685 patients with early and advanced NSCLC diagnosed between 2009 and 2014 was conducted with collection of clinical, and laboratory data. The IPI was calculated as C-reactive protein ${\times}$ NLR (neutrophil/ lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The optimal cut-off value of IPI for overall survival (OS) stratification was determined to be 15. Totals of 334 (48.8%) and 351 (51.2%) patients were assigned to high and low IPI groups, respectively. Compared with low IPI, high IPI was associated with older age, greater tumor size, high lymph node involvement, distant metastases, advanced stage and poor performance status. Median OS was worse in the high IPI group (low vs high, 8.0 vs 34.0 months; HR, 3.5; p<0.001). Progression free survival values of the patients who had high vs low IPI were determined 6 months (95% CI:5.3-6.6) and 14 months (95% CI:12.1-15.8), respectively (HR; 2.4, P<0.001). On multivariate analysis, stage, performance status, lactate dehydrogenase and IPI were independent prognostic factors for OS. Subgroup analysis showed IPI was generally a significant prognostic factor in all clinical variables. Conclusion: The described IPI may be an inexpensive, easily accessible and independent prognostic index for NSCLC patients, useful for clinical practice.
Estimated Risk of Radiation Induced Contra Lateral Breast Cancer Following Chest Wall Irradiation by Conformal Wedge Field and Forward Intensity Modulated Radiotherapy Technique for Post-Mastectomy Breast Cancer Patients
Athiyaman, Hemalatha;M, Athiyaman;Chougule, Arun;Kumar, HS 5107
Background: Epidemiological studies have indicated an increasing incidence of radiation induced secondary cancer (SC) in breast cancer patients after radiotherapy (RT), most commonly in the contra-lateral breast (CLB). The present study was conducted to estimate the SC risk in the CLB following 3D conformal radiotherapy techniques (3DCRT) including wedge field and forward intensity modulated radiotherapy (fIMRT) based on the organ equivalent dose (OED). Material and Methods: RT plans treating the chest wall with conformal wedge field and fIMRT plans were created for 30 breast cancer patients. The risks of radiation induced cancer were estimated for the CLB using dose-response models: a linear model, a linear-plateau model and a bell-shaped model with full dose response accounting for fractionated RT on the basis of OED. Results: The plans were found to be ranked quite differently according to the choice of model; calculations based on a linear dose response model fIMRT predict statistically significant lower risk compared to the enhanced dynamic wedge (EDW) technique (p-0.0089) and a non-significant difference between fIMRT and physical wedge (PW) techniques (p-0.054). The widely used plateau dose response model based estimation showed significantly lower SC risk associated with fIMRT technique compared to both wedge field techniques (fIMRT vs EDW p-0.013, fIMRT vs PW p-0.04). The full dose response model showed a non-significant difference between all three techniques in the view of second CLB cancer. Finally the bell shaped model predicted interestingly that PW is associated with significantly higher risk compared to both fIMRT and EDW techniques (fIMRT vs PW p-0.0003, EDW vs PW p-0.0032). Conclusion: In conclusion, the SC risk estimations of the CLB revealed that there is a clear relation between risk associated with wedge field and fIMRT technique depending on the choice of model selected for risk comparison.
Adolescents' Perceptions Regarding Effective Tobacco Use Prevention Strategies for their Younger Counterparts: A Qualitative Study in Malaysia
Zin, Faridah Mohd;Hillaluddin, Azlin Hilma;Mustaffa, Jamaludin 5113
Purpose:The present qualitative study explored adolescents' perceptions regarding effective strategies to prevent adolescents from using tobacco products (TP). Apart from the commercial TPs, there has been emerging use of alternatives such as vapes, e-cigarettes and shisha. This unfortunate phenomenon continues despite the currently available preventive strategies. Thus, understanding of the perceptions of the current generation would be valuable to provide new insights. Methods: Purposive sampling was utilized to recruit 40 adolescents between the age of 15 and 16 years old attending public daily secondary schools. Eight focus group discussions were conducted among the TP users, ex-users and non-users. Data were analyzed using a thematic content analysis procedure with NVivo. Results: Among barriers with the currently available strategies were having teachers who smoke tobacco, addiction to nicotine and self-perceptions of being healthy. The content of any program should include knowledge on negative outcomes of using tobacco products and awareness of the legislation together with ways to overcome peer and family influence including improving self-efficacy and refusal skills. Strategies were suggested to be delivered using information technology which provides interactive learning and visual effects. Conclusions: Adolescents agreed that the content and delivery of tobacco use prevention strategies need to be revised to suit the current generation to ensure sustainability.
Health Related Quality of Life (HRQoL) among Breast Cancer Patients Receiving Chemotherapy in Hospital Melaka: Single Centre Experience
Chean, Dang Chee;Zang, Wong Kuo;Lim, Michelle;Zulkefle, Nooraziah 5121
Objective: To investigate the impact of chemotherapy on quality of life (QoL) among breast cancer patients and to evaluate the relationship with age, cancer stage and presence of any comorbidity. Methods: A prospective study was conducted among breast cancer patients receiving chemotherapy in Hospital Melaka from 1st January 2014 to 31st July 2014. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was given to patients to fill in prior chemotherapy (baseline) and after the third cycle of chemotherapy. Socio-demographic and clinical data were collected and analyzed using SPSS version 20. Result: Respondents were 32 female patients [mean age (SD): 49.7(9.93) years]. They reported a significant lower global health status (P < 0.01) and significant higher symptoms of nausea and vomiting (P < 0.01), loss of appetite (P = 0.028) and diarrhea (P = 0.026) after the third cycle of chemotherapy as compared to baseline. Compare to, this study showed significant better emotional functioning (P < 0.01) and social functioning (P < 0.01) than the EORTC QLQ-C30 Reference Values 2008 for breast cancer cases. Under symptom scales higher scores were noted for appetite loss (P = 0.017), nausea and vomiting (P < 0.01). Age, stage and comorbidity had no clear associations with global health status in our patients (P > 0.05). Conclusion: Chemotherapy did reduce the QoL of breast cancer patients. Management of chemotherapy-induced loss of appetite, diarrhea, nausea and vomiting should be improved for a better outcome.
Internal Motivation, Perceived Health Competency, and Health Literacy in Primary and Secondary Cancer Prevention
Jung, Su Mi;Jo, Heui Sug;Oh, Hyung Won 5127
Objective: The aim of this study was to identify associations of internal motivation, perceived health competency, and health literacy with primary and secondary cancer prevention. Methods: A telephone survey was conducted with a sample of 2,700, 30-69 year olds, proportionally extracted from Gangwon Province, South Korea. The dependent variables were actions in primary and secondary prevention and the explanatory variables were 13 questions in three areas: internal motivation (4 items), perceived health competency (4 items), and health literacy (5 items). Result: Multiple linear regression analysis showed that internal motivation, perceived health competency, and health literacy positively impacted primary prevention after controlling for gender and age. As internal motivation, perceived health competency, and perceived literacy increased by 1 point, primary prevention scores increased by 0.11, 0.11, and 0.07 points, respectively. In addition, logistic regression results for secondary prevention showed that health literacy had a positive impact on secondary behavior. As health literacy increased by 1 point, the odds ratio of the practice of secondary prevention was 1.4 times higher. Conclusion: This study suggests that primary and secondary prevention of cancer are significantly related to intrinsic motivation factors, perceived health competency, and actual health literacy. Health literacy concepts that cover the capacity of health management in comprehensive areas need to be applied to education and promotion for improvement of primary and secondary prevention of cancer.
Self-Care Education Programs Based on a Trans-Theoretical Model in Women Referring to Health Centers: Breast Self-Examination Behavior in Iran
Ghahremani, Leila;Mousavi, Zakiyeh;Kaveh, Mohammad Hossein;Ghaem, Haleh 5133
Background: Breast cancer is one of the most common cancers and a major public health problem in developing countries. However, early detection and treatment may be achieved by breast self-examination (BSE). Despite the importance of BSE in reducing the incidence of breast cancer and esultant deaths, the disease continues to be the most common cause of cancer death among women in Iran.This study aimed to determine the effects of self-care education on performance of BSE among women referring to health centers in our country. Materials and Methods: This quasi-experimental interventional study with pretest/posttest control group design was conducted on 168 women referred to health centers. The data were collected using a validated researcher-made questionnaire including demographic variables and trans-theoretical model constructs as well as a checklist assessing BSE behavior. The instruments were administered to groups with and without self-care education before, a week after, and 10 weeks after the intervention. Then, the data were entered into the SPSS statistical software (version 19) and analyzed using independent sample t-tests, paired sample t-test, repeated measures ANOVA, Chi-square, and Friedman tests (p<0.05). Results: The results showed an increase in the intervention group's mean scores of trans-theoretical model constructs (stages of change, self-efficacy, decisional balance, and processes of change) and BSE behavior compared to the control group (p<0.001). Conclusion: The study confirmed the effectiveness of aneducational intervention based ona trans-theoretical model in performing BSE. Therefore, designing educational interventions based on this model is recommended to improve women's health and reduce deaths due to breast cancer.
The Effects of Purified Artemia Extract Proteins on Proliferation, Differentiation and Apoptosis of Human Leukemic HL-60 Cells
Deezagi, Abdolkhaleg;Chashnidel, Azadeh;Hagh, Neda Vaseli;Shahraki, Mahvash Khodabandeh 5139
There has been an increment in the number of studies focused on marine bioactive materials. Many peptides and other biomaterials with anticancer potential have been extracted from various marine animals. Artemia extracts have found uses in sun-light protection cosmetics and anti-aging products. However, contents of biochemical compounds in Artemia spp. and molecular mechanisms of have not been clearly studied in leukemic cells in vitro. In this work, we isolated and purified proteins of Artemia Urmiana. Six clear fractions (A-F) observed on DEAE-cellulose chromatography were assayed for effects on cell growth, differentiation and apoptosis using the human leukemic HL-60 cell line. Cell proliferation analysis by MTT and BrdU assays indicated that did not affect cells, growth. Cells treated with crude extract and fractions A, B and C, but not E and F (up to $100{\mu}g/mL$), exhibited increase of cell growth in a dose dependent manner. Stimulatory effects of fraction D were observed at concentrations of $10{\mu}g/mL$ and above. In nitro blue tetrazolium (NBT) reduction assays, treatment with $100{\mu}g/mL$ of fraction E or F for 96 hr increased the fraction of differentiated cells up to $14.8{\pm}3.56%$ and $16.5{\pm}2.08%$ respectively. Combination of those fractions with retinoic acid had significant synergistic effects on the differentiation of cells ($56.8{\pm}3.7%$ and $67.4{\pm}4.2%$, $p{\leq}0.01$). Annexin-V FITC staining for apoptosis and flow cytometric assays indicated induction of apoptosis by fractions E and F up to 23.8 and 31.8% of cells.
Sensitive High-Resolution Melting Analysis for Screening of KRAS and BRAF Mutations in Iranian Human Metastatic Colorectal Cancers
Niya, Mohammad Hadi Karbalaie;Basi, Ali;Koochak, Aghigh;Tameshkel, Fahimeh Safarnezhad;Rakhshani, Nasser;Zamani, Farhad;Imanzade, Farid;Rezvani, Hamid;Adib sereshki, Mohammad Mahdi;Sohrabi, Masoud Reza 5147
Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.
Organization and Evaluation of Performance Indicators of a Breast Cancer Screening Program in Meknes-Tafilalt Region, Morocco
Charaka, Hafida;Khalis, Mohamed;Elfakir, Samira;Khazraji, Youssef Chami;Zidouh, Ahmed;Abousselham, Loubna;El Rhazi, Karima;Lyoussi, Badiaa;Nejjari, Chakib 5153
Objective: The benefits of screening and early detection of breast cancer, including reduced morbidity and mortality, have been well-reported in the literature. In 2011, a breast cancer screening program was launched in Meknes-Tafilalt region of Morocco. The aim of this study was to evaluate the early performance indicators of this program. Materials and Methods: This retrospective evaluative study was conducted between April 2012 and December 2014, in Meknes-Tafilalt region of Morocco. Several performance indicators of the breast cancer screening program were calculated: the compliance rate, the positivity rate, the referral rate, the cancer detection rate and the organizational indicators. Results: During 2012-2014, a total of 184,951 women participated in the breast cancer screening program. The compliance rate was 26%, the positive rate was 3.3%, the referral rate was 36.7%, and the cancer detection rate was 1.2 per 1,000 women. The median time between the date of clinical breast examination and the date of biopsy (or cyto-puncture) was 36 days. The median time between the date of positive mammography and the date of biopsy (or cyto-puncture) was 6 days. The median time between the date of clinical breast examination and the date of the first received treatment was 61 days. Conclusions: The program needs better monitoring, as well as implementation of quality assurance tools to improve performance in our country.
Morbidity, Disability and Death Rates of The Population Due to Malignant Neoplasms in Uralsk City in The Republic of Kazakhstan
Umarova, Gulmira;Mamyrbayev, Arstan;Bermagambetova, Saule;Baspakova, Akmaral;Satybaldieva, Umyt;Sabyrakhmetova, Valentina;Abilov, Talgar;Sultanova, Gulnar;Uraz, Raisa 5159
Objective: The dynamics of morbidity, disability and death rates due to malignant neoplasms in the population in Uralsk city of the Republic of Kazakhstan were studied for 2011-2015, with a focus on age and sex, as well as tumor location. Methods: Statistics for total morbidity, primary disability and mortality from cancer in the adult population of the city of Uralsk for 2011-2015 were calculated per 100 thousand. Estimation of morbidity was based on data from form - $N{\underline{o}}12$ ${\ll}$Report on the number of diseases registered in patients living in the area of health care organizations and patient population under medical observation". Evaluation of primary disability was based on form $N{\underline{o}}7$ ${\ll}$The distribution of newly recognized disabled by disease class, age, sex and disability groups" for 2011-2015 in Ural city and analysis of cancer was carried out using annual form 7 "Report on the sick, and diseases of malignant neoplasms". Result: The most common localizations of cancer were the trachea, bronchi, lungs, stomach and mammary glands. High death rates were noted for patients with cancer of the trachea, bronchi, lung, as compared to stomach and esophagus. Conclusion: The results of our investigation and data in the literature indicate that regional characteristics influence the impact of risk factors associated with cancer. An unfavorable environmental background contributes to ill health of urban populations, contributing to development of cancer. Moreover behavioral risk factors are very important, such as smoking, alcohol drinking, and an unhealthy diet. All these factors require urgent adoption of a package of measures for prevention, early detection and timely treatment. Detailed study of cancer is necessary to develop national programs and activities for prevention and control.
Diet-Related Stomach Cancer Behavior Among Iranian College Students: A Text Messaging Intervention
Dehdari, Tahereh;Dehdari, Laleh;Jazayeri, Shima 5165
Background: Stomach cancer is one of the five most common cancers in Iran. This study examined the effectiveness of a mobile telephone short-message service (SMS) based-education intervention using Health Belief Model (HBM) variables in improving dietary behavior in terms of stomach cancer prevention among a sample of Iranian female college students. Materials and Methods: In this quasi-experimental study, 124 female college students in the dormitories of Yazd University, Yazd, Iran were randomly selected and assigned to either the intervention (n=62) or the control group (n=62). Information (data) regarding HBM variables and dietary behavior related to stomach cancer prevention was collected by a self-administrated questionnaire. Forty eight messages were designed and sent to the participants' phones in the intervention group during the 48-day intervention period. Two groups were followed-up one month after the intervention delivered via SMS. Results: There were significant differences in HBM variables (except for the perceived severity) and the preventive dietary behaviors for stomach cancer in the intervention group compared to the comparison group following the education intervention delivered via SMS. Conclusions: SMS-delivered nutrition education intervention can be a practical strategy to improve dietary behavior related to stomach cancer prevention.
Lack of Altered BECN1 Gene Expression in Iranian Patients with Acute Myeloid Leukemia
Keyvan, Ladan;Bidoki, Seyed Kazem;Abdollahi, Davood Zare;Mansouri, Neda;Hashemi, Mehrdad;Tabatabaei, SA Mortazavi;Fardmanesh, Hediyeh;Meimandi, Mansour;Ayatollahi, Seyed Majid;Movafagh, Abolfazl 5173
Acute myeloid leukemia (AML), one of the most prevalent leukemia types in adults, demonstrates great heterogeneity in molecular and clinical terms. Hence, there is a necessity to the mechanisms involved in AML generation in order to determine optimal treatment. This cross sectional study aimed to assess changes in BECN1 gene expression in with blood samples from 30 AML patients, compared with samples from 15 healthy persons. RNA was extracted and cDNA was synthesized and Real Time PCR applied to determine BECN1 gene expression. The results showed no significant differences in BECN1 gene expression between patients with AML and normal controls (P > 0.05). It appears that expression of BECN1 does not play a significant role in genesis of AML leukemia.
Prognostic Value of Prepro-Gastrin Releasing Peptide in Lung Cancer Patients; NCI-Prospective Study
Shafik, Nevine F;Rahoma, M;Elshimy, Reham AA;El kasem, Fatma M Abou 5179
Background: Prior series investigated the expression of prepro-gastrin releasing peptide (prepro-GRP) in the peripheral blood of lung cancer patients. Our aim was to assess any prepro-GRP role as a prognostic factor for small cell lung cancer (SCLC) and NSCLC and correlations with clinical presentation and treatment outcome. Methods: A prospective study was conducted during the time period from the beginning of January 2012 till the end of January 2014. Prepro-GRP expression was analysed using a nested RT-PCR assay in peripheral blood of 62 untreated lung cancer patients attending the National Cancer Institute (NCI), Cairo University, and 30 age and sex matched healthy volunteers. Results: Among the 62 lung cancer cases, there were 24 (38.7%) SCLC, and 38 (61.3%) NSCLC (10 squamous cell carcinomas, 12 adenocarcinomas, 11 large cell carcinomas, 4 undifferentiated carcinomas, and 1 adenosquamous carcinoma). Twenty six patients (41.9%) were prepro-GRP positive. Prepro-GRP expression was higher (58.3%) among SCLC patients compared to NSCLC (squamous cell carcinoma (15.4%), large cell carcinoma (36.4%), and adenocarcinoma (25%)). Mean OS among prepro-GRP negative cases was longer than that among preprogastrin positive cases (17.6 vs 14.9 months). The mean PFS durations among preprogastrin negative versus positive cases were 7.7 vs 4.6 months (p= 0.041). No difference in response to chemotherapy was identified between the groups (p=0.983). Conclusion: Prepro-GRP is suggested to be a useful prognostic marker for lung cancer patients, especially with the fast- growing, bad prognostic SCLC type. More studies should aim at detailed understanding of the mechanisms of prepro-GRP action and its use in monitoring the response to treatment in a larger cohort.
Folate-Targeted Nanostructured Lipid Carriers (NLCs) Enhance (Letrozol) Efficacy in MCF-7 Breast Cancer Cells
Sabzichi, Mehdi;Mohammadian, Jamal;Khosroushahi, Ahmad Yari;Bazzaz, Roya;Hamishehkar, Hamed 5185
Objective: Targeted-drug-delivery based lipid nanoparticles has emerged as a new and effective approach in cancer chemotherapy. Here, we investigated the ability of folate-modified nanostructured lipid carriers (NLCs) to enhance letrozol (LTZ) efficacy in MCF-7 breast cancer cells. Methods: New formulations were evaluated regarding to particle size and scanning electron microscope (SEM) features. Anti-proliferative effects of LTZ loaded nanoparticles were examined by MTT assay. To understand molecular mechanisms of apoptosis and cell cycle progression, flow cytometric assays were applied. Results: Optimum size of nanoparticles was obtained in mean average of $98{\pm}7nm$ with a poly dispersity index (PDI) of 0.165. The IC50 value was achieved for LTZ was $2.2{\pm}0.2{\mu}M$. Folate-NLC-LTZ increased the percentage of apoptotic cells from 24.6% to 42.2% compared LTZ alone (p<0.05). Furthermore, LTZ loaded folate targeted NLCs caused marked accumulation of cells in the subG1 phase. Conclusion: Taken together, our results concluded that folate targeted LTZ can be considered as potential delivery system which may overcome limitations of clinical application of LTZ and improve drug efficacy in tumor tissue.
Induction of Apoptosis and Cell Cycle Arrest by Dorema Glabrum Root Extracts in a Gastric Adenocarcinoma (AGS) Cell Line
Jafari, Naser;Zargar, Seyed Jalal;Yassa, Narguess;Delnavazi, Mohammad Reza 5189
Objective: Dorema glabrum Fisch. & C.A. Mey is a perennial plant that has several curative properties. Anti-proliferative activity of seeds of this plant has been demonstrated in a mouse fibrosarcoma cell line. The aim of the present study was to evaluate cytotoxicity of D. glabrum root extracts in a human gastric adenocarcinoma (AGS) cell line and explore mechanisms of apoptosis induction, cell cycle arrest and altered gene expression in cancer cells. Materials and Methods: The MTT assay was used to evaluate IC50 values, EB/AO staining to analyze the mode of cell death, and flow cytometry to assess the cell cycle. Quantitative real-time polymerase chain reaction (qRT-PCR) amplification was performed with apoptosis and cell cycle-related gene primers, for cyclin D1, c-myc, survivin, VEGF, Bcl-2, Bax, and caspase-3 to determine alteration of gene expression. Results: Our results showed that n-hexane and chloroform extracts had greatest toxic effects on gastric cancer cells with IC50 values of $6.4{\mu}g/ml$ and $4.6{\mu}g/ml$, respectively, after 72 h. Cell cycle analysis revealed that the population of treated cells in the G1 phase was increased in comparison to controls. Cellular morphological changes indicated induction of apoptosis. In addition, mRNA expression levels of Bax and caspase-3 were increased, and of bcl-2 survivin, VEGF, c-myc and cyclin D1 were decreased. Conclusion: Our study results suggest that D. glabrum has cytotoxic effects on AGS cells, characterized by enhanced apoptosis, reduced cell viability and arrest of cell cycling.
Association of The IDH1 C.395G>A (R132H) Mutation with Histological Type in Malay Brain Tumors
Yusoff, Abdul Aziz Mohamed;Zulfakhar, Fatin Najwa;Sul'ain, Mohd Dasuki;Idris, Zamzuri;Abdullah, Jafri Malin 5195
Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors.
The Incidence of Malignant Tumors in Environmentally Disadvantaged Regions of Kazakhstan
Mamyrbayev, Arstan;Djarkenov, Timur;Dosbayev, Askar;Dusembayeva, Nailya;Shpakov, Anatolyi;Umarova, Gulmira;Drobchenko, Yelena;Kunurkulzhayev, Temirgali;Zhaylybaev, Mukhtar;Isayeva, Gulnar 5203
Objective: To explore the prevalence of malignant tumors in the adult population through 2003-2014 in parts of the Aral Sea region: a zone of ecological disaster, a zone of ecological crisis and a zone of precritical conditions. Methods: The long-time average annual levels of cancer morbidity stratified by zones of the Aral Sea region and trends of long-time average annual incidence indicators of malignant tumors were identified. Leading cancer localizations in the adult population was established and associations between cancer incidence and environmental pollution were analyzed. In addition, associations between individual risk factors and cancer incidence in the adult population was established. Correlations between a hazard index and the cancer incidence in the adult population were calculated. Results: In all three Aral Sea regions, as well as in Zhanaarkinskii district, leading cancer in adult population was esophageal, stomach, tracheal, lung, hepatobiliary, and breast. Long-time average annual levels of cancer morbidity in adult population living in the Aral sea region is 1.5 times higher comparing to the control region. In particular, long-time average annual levels of cancer morbidity in adult population living in the zone of ecological disaster was 57.2% higher, in the zone of ecological crisis - 61.9% higher, and in the zone of precritical condition - 16.8% higher. Long-time average annual levels in the adult population of the Aral Sea region significantly exceeded control levels for brain and central nervous system cancer, cancer of bone and articular cartilage, and thyroid cancer. Conclusion: It has was established that the total cancer morbidity depended on the total hazard index associated with the inhalation of nickel and the combined cadmium intake (r=0.8).
Female Breast Cancer Incidence and Mortality in Morocco: Comparison with Other Countries
Khalis, Mohamed;El Rhazi, Karima;Charaka, Hafida;Chajes, Veronique;Rinaldi, Sabina;Nejjari, Chakib;Romieu, Isabelle;Charbotel, Barbara 5211
Background: Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer death among women worldwide. In Morocco, there have been few recent descriptive studies on female breast cancer. The aim of this study was to describe the latest available incidence and mortality rates of breast cancer among Moroccan women and to compare them with rates in other regional and Western countries. Methods: For this descriptive study, Moroccan incidence data were obtained from the most recent reports of the cancer registries of Casablanca and Rabat. Information on breast cancer incidence for different countries were obtained primarily from publicly available cancer registries and Cancer Incidence in Five Continents, Volume X. Mortality data were extracted from the GLOBOCAN 2012 published by the International Agency for Research on Cancer. Results: The age-standardized incidence (World) rate of breast cancer in Moroccan women increased from 35.0 to 39.0 per 100,000 women between 2004 and 2008, showing an annual increase of 2.85 %. The highest incidence rates were registered in the age groups of 45-49, 50-54 and 55-59 years (106.1, 108.2 and 108.5 respectively). Sixty-nine percent of female breast cancer cases were diagnosed at stages II and III. In 2012, the estimated number of women who died of breast cancer in Morocco was 2,878. The crude, age-standardized (World) mortality rates were 17.3 and 18.0 per 100,000, respectively. Conclusion: Although the incidence of female breast cancer in Morocco is lower than in Western countries, evidence shows that the rate is rising. This increase of breast cancer incidence has been observed in parallel with changes in reproductive behavior and adoption of a Western lifestyle. Prevention policies need to be implemented.
Features of Malignancy Prevalence among Children in the Aral Sea Region
Mamyrbayev, Arstan;Dyussembayeva, Nailya;Ibrayeva, Lyazzat;Satenova, Zhanna;Tulyayeva, Anara;Kireyeva, Nurgul;Zholmukhamedova, Dinara;Rybalkina, Dina;Yeleuov, Galymzhan;Yeleuov, Almasbek 5217
Objective: A study of primary cancer morbidity among children and subsequent calculation of average annual incidence were carried out for boys and girls, and young men and women in Kazakhstan. Methods: The investigated population lived in three areas of the Aral Sea region: designated catastrophe (Aral, Kazalt, Shalkar regions), crisis (Zhalagash, Karmakshy, Shiely regions), pre-crisis (Irgiz, Arys, Ulytau regions). Zhanaarka region of Karaganda oblast was applied as a control. Parameters were retrospective analyzed for the 10 years from 2004 to 2013. Result: The results indicate that indices of children cancer morbidity were slightly higher in the Aral Sea region than in the control district, but they were comparable with similar data from studies in other regions. In all areas of the Aral Sea region, except for Ulytau, primary cancer morbidity exceeded the control level by 1.3-2.7 times (4.7%000). Hematological malignancies, including solid tumors - tumors of musculoskeletal system and skin, digestive system, brain and central nervous system predominated. Stress levels in zones of the Aral Sea region were slightly higher in the crisis zone than in the catastrophe zone that can be explained by the phenomenon of wave-like dynamics of disease growth risk. Gender differences in characteristics of malignancy formation were not more pronounced in the studied region. Conclusion: Indices of children cancer are slightly higher in the Aral Sea region than in the control area of Kazakhstan, but they are comparable to results for other regions.
Comparison Between Two Detection Methods for HPV16, HPV18 and P16Ink4a Biomarkers in Diagnosis of Abnormal Cervical Cytology
Khazaei, Sedigheh;Izadi, Babak;Mirbahari, Seyed Ghasem;Madani, Seyed Hamid;Khosravi, Shohre Malek;Alagha, Mohsen Emami;Sajadimajd, Soraya 5223
Background: Cervical cancer is the second most common cancer among women in many populations. While the Pap smear is a well established screening test it suffers from both false-positive and false-negative results in diagnosis of cancers and precancerous states. In this study, immunocytochemistry of the P16 biomarker and HPV-PCR were compared for their diagnostic potential. Materials and methods: In the study, we obtained pairs of specimens from 45 women with cervical dysplasia. One sample was placed in a liquid-based solution, and processed for staining of sections with antibodies to P16. HPV-PCR was performed on the other and the results obtained were analyzed by T-test using SPSS v. 15. Results: Using HPV-PCR 71% of the samples were found to be infected with either HPV 16 or HPV 18, and the rate of infection did not have a statistically significant relationship with higher grades of dysplasia (p= 0.253). In contrast, with immunocytochemistry evaluation of P16, 64% of the specimens were positive, but the percentage of positive results significantly increased with higher grades of dysplasia (p= 0.0001). Conclusion: Employment of the P16 marker as an optional test might be preferable over HPV-PCR for cervical dysplasia in our geographical region.
Evaluation of Combined Quantification of PCA3 and AMACR Gene Expression for Molecular Diagnosis of Prostate Cancer in Moroccan Patients by RT-qPCR
Maane, Imane Abdellaoui;El Hadi, Hicham;Qmichou, Zineb;Al Bouzidi, Abderrahmane;Bakri, Youssef;Sefrioui, Hassan;Dakka, Nadia;Moumen, Abdeladim 5229
Prostate cancer (PCa) remains one of the most widespread and perplexing of all human malignancies. Assessment of gene expression is thought to have an important impact on cancer diagnosis, prognosis and therapeutic decisions. In this context, we explored combined expression of PCa related target genes AMACR and PCA3 in 126 formalin fixed paraffin embedded prostate tissues (FFPE) from Moroccan patients, using quantitative real time reverse transcription-PCR (RT-qPCR). This quantification required data normalization accomplished using stably expressed reference genes (RGs). A panel of twelve RG was assessed, data being analyzed using GenEx V6 based on geNorm, NormFinder and statistical methods. Accordingly, the hnRNP A1 gene was identified and selected as the most stably expressed RG for reliable and accurate gene expression quantification in prostate tissues. The ratios of both PCA3 and AMACR gene expression relative to that of the hnRNP A1 gene were calculated and the performance of each target gene for PCa diagnosis was evaluated using receiver-operating characteristics. PCA3 and AMACR mRNA quantification based on RT-qPCR may prove useful in PCa diagnosis. Of particular interesting, combining PCA3 and AMACR quantification improved PCa prediction by increasing sensitivity with retention of good specificity.
Readability Comparison of Pro- and Anti-Cancer Screening Online Messages in Japan
Okuhara, Tsuyoshi;Ishikawa, Hirono;Okada, Masahumi;Kato, Mio;Kiuchi, Takahiro 5237
Background: Cancer screening rates are lower in Japan than those in western countries. Health professionals publish procancer screening messages on the internet to encourage audiences to undergo cancer screening. However, the information provided is often difficult to read for lay persons. Further, anti-cancer screening activists warn against cancer screening with messages on the Internet. We aimed to assess and compare the readability of pro- and anti-cancer screening online messages in Japan using a measure of readability. Methods: We conducted web searches at the beginning of September 2016 using two major Japanese search engines (Google.jp and Yahoo!.jp). The included websites were classified as "anti", "pro", or "neutral" depending on the claims, and "health professional" or "non-health professional" depending on the writers. Readability was determined using a validated measure of Japanese readability. Statistical analysis was conducted using two-way ANOVA. Results: In the total 159 websites analyzed, anti-cancer screening online messages were generally easier to read than pro-cancer screening online messages, Messages written by health professionals were more difficult to read than those written by non-health professionals. Claim ${\times}$ writer interaction was not significant. Conclusion: When health professionals prepare pro-cancer screening materials for publication online, we recommend they check for readability using readability assessment tools and improve text for easy comprehension when necessary.
Expression of Bone Morphogenetic Protein-2 and Histological Differentiation of Oral Squamous Cell Carcinomas
Hamasni, Fatme Mouchref;El Hajj, Fady 5243
Background and Objective : Bone morphogenic protein-2 (BMP-2) plays an essential role in mesenchymal cell differentiation into osteoblasts، through many intracellular pathways which may also be active in tumors. Invasive oral squamous cell carcinomas account for more than 90% of head and neck malignancies in many cancer registries. They are classified into three types according to epithelial cell differentiation. The present study aimed to identify any relation between BMP-2 expression and tumor histology. Materials and methods: BMP-2 expression was compared immunohistochemically among 30 cases (19 male and 11 female, mean age 48 years) of oral squamous cell carcinoma, Division was into 3 groups (each containing 10 cases) according to the histological grade. Results: No significant correlation between BMP-2 expression and histological grade was observed. Changes in localization and cytoplasmic staining were also not apparent. Conclusion: From the results of this study BMP-2 does not appear to have any application as a prognostic marker for oral squamous cell carcinomas.
Evaluation of the Pathogenesis of Tumor Development from Endometriosis by Estrogen Receptor, P53 and Bcl-2 Immunohistochemical Staining
Esmaili, Haidarali;Vahedi, Amir;Mohajeri, Shiva;Mostafidi, Elmira;Azimpouran, Mahzad;Behzad, Mohammad Naghavi 5247
Objective: Endometriosis, one of the most common estrogen dependent gynecological disorders, can present as both benign and malignant disease. The prevalence of tumoral transformation is 0.7-1.6% and the most common tumors are clear cell and endometrioid carcinomas. Unfortunately, the pathogenesis of transformation is unknown. For this purpose, we examined molecular alterations in ovarian endometriosis and endometriosis-associated tumors. Methods: Using the data bank of Alzahra hospital pathology department and paraffin blocks from appropriate cases were identified. Sections were cut and stained for 3 markers: estrogen receptor, P53 and bcl2. Correlations between findings were investigated. Results: Nineteen cases of endometriosis-associated tumor and 19 cases of endometriosis were identified. Staining for bcl2 was documented in 14 of 19 (73.7%) of endometriosis-associated tumor cases and also 7 of 19 (36.8%) endometriosis cases (P=0.02). Only 3 of the 19 (15.8%) endometriosis-associated tumors exhibited positive staining for estrogen receptors, compared with 14 of 19 (73.7%) endometriosis cases (P<0.001). Positive staining for P53 was noted in 5 of 19 (31.6%) endometriosis-associated ovarian tumor samples but was absent in endometriosis samples (0%), (P =0.008). Conclusions: Endometriosis-associated tumors appear to be associated with overexpression of bcl2 and P53 and reduced expression of Estrogen receptor. These finding may help to diagnose tumoral transformation with a background of endometriosis.
Outcomes of 1st Remission Induction Chemotherapy in Acute Myeloid Leukemia Cytogenetic Risk Groups
Zehra, Samreen;Najam, Rahela;Farzana, Tasneem;Shamsi, Tahir Sultan 5251
Background: Diagnostic karyotyping analysis is routinely used in acute myeloid leukemia (AML) clinics. Categorization of patients into risk stratified groups (favorable, intermediate and adverse) according to cytogenetic findings can serve as a valuable independent prognostic factor. Method and Material: A retrospective descriptive study was conducted based on the patient records of newly diagnosed non-M3 AML young adult cases undergoing standard 3+7 i.e, Daunorubicin and Ara-C (DA) as remission induction chemotherapy. Diagnostic cytogenetic analysis reports were analyzed to classify the patients into risk stratified groups according to South West Oncology Group criteria and prognostic significance was measured with reference to achievement of haematological remission after 1st induction chemotherapy. Results:A normal karyotype was commonly expressed, found in 47.2% of patients, while 65% (n=39) appeared to have intermediate risk cytogenetics, and 13.3% (n=8) adverse or unclassified findings. Favourable cytogenetics was least frequent in the patient cohort, accounting for only 8.3 % (n=5).The impact of cytogenetic risk groups on achievement of haematological remission was evaluated by applying Pearson Chi-square, and was found to be non-significant (df=12, p=0.256) but when the outcomes of favourable risk groups with intermediate, adverse and unclassified findings compared, results were highly significant (df=6, p=0.000) for each comparison. In patients of the favourable cytogenetic risk group, HR?? was reported in 40% (n=2/5), as compared to 62.2% (n=23/37) in the intermediate cytogenetic risk group, 57.1% (n=4/7) in the adverse cytogenetic risk group and 28.6% (n=2/7) in hte unclassified cytogenetic risk group. Conclusion: Cytogenetic risk stratification for AML cases following criteria provided by international guidelines did not produce conclusive results in our Pakistani patients. However, we cannot preclude an importance as the literature clearly supports the use of pretreatment karyotyping analysis as a significant predictive marker for clinical outcomes. The apparent differences between Pakistani and Western studies indicate an urgent need to develop risk stratification guidelines according to the specific cytogenetic makeup of South Asian populations.
Skin Cancer Concerns in People of Color: Risk Factors and Prevention
Gupta, Alpana K;Bharadwaj, Mausumi;Mehrotra, Ravi 5257
Background: Though people of color (POC) are less likely to become afflicted with skin cancer, they are much more likely to die from it due to delay in detection or presentation. Very often, skin cancer is diagnosed at a more advanced stage in POC, making treatment difficult.The purpose of this research was to improve awareness regarding skin cancers in people of color by providing recommendations to clinicians and the general public for early detection and photo protection preventive measures. Methods: Data on different types of skin cancers were presented to POC. Due to limited research, there are few resources providing insights for evaluating darkly pigmented lesions in POC. Diagnostic features for different types of skin cancers were recorded and various possible risk factors were considered. Results: This study provided directions for the prevention and early detection of skin cancer in POC based on a comprehensive review of available data. Conclusions: The increased morbidity and mortality rate associated with skin cancer in POC is due to lack of awareness, diagnosis at a more advanced stage and socioeconomic barriers hindering access to care. Raising public health concerns for skin cancer prevention strategies for all people, regardless of ethnic background and socioeconomic status, is the key to timely diagnosis and treatment.
Evaluation of Invasive and Noninvasive Methods for the Diagnosis of Helicobacter Pylori Infection
Cosgun, Yasemin;Yildirim, Abdullah;Yucel, Mihriban;Karakoc, Ayse Esra;Koca, Gokhan;Gonultas, Alpaslan;Gursoy, Gul;Ustun, Huseyin;Korkmaz, Meliha 5265
Objective: The present study was conducted to evaluate invasive and noninvasive diagnostic methods for detection of Helicobacter pylori (H. pylori) in patients admitted with dyspeptic complaints and to compare sensitivities and specificities. Method: Sets of four gastric biopsy specimens were obtained from a total of 126 patients included in the study. The presence of H. pylori was determined by invasive tests including culture, rapid urease test, polymerase chain reaction (PCR) and histopathology. Among noninvasive tests, urea breath test, serological tests and enzyme-linked immunosorbent assay (ELISA) were performed. Results: H. pylori was isolated in 79 (62.7%) gastric biopsy cultures, whereas positivity was concluded for 105 (83.3%) patients by rapid urease test, for 106 (84.1%) by PCR, for 110 (87.3%) by histopathology, for 119 (94.4%) by urea breath test, and for 107 (84.9%) by ELISA. In the present study, the culture findings and histopathological examination findings were accepted as gold standard. According to the gold standard, urea breath test had the highest sensitivity (96.5%) and the lowest specificity (30%), whereas culture and histopathology had the highest specificities (100%). Conclusion: The use of PCR invasively with gastric biopsy samples yielded parallel results with the gold standard. PCR can be recommended for routine use in the diagnosis of H. pylori.
Diagnostic and Prognostic Relevance of Bone Marrow Microenvironment Components in Non Hodgkin's Lymphoma Cases Before and After Therapy
Soliman, Amira H 5273
Objective: To evaluate stromal cells of the bone marrow microenvironment (BMM) in bone marrow trephine biopsy (BMTB) specimens, with a focus on fibronectin, tumor necrosis factor- alpha (TNF-${\alpha}$) and L-selectin in Non-Hodgkin's lymphoma (NHL) patients, before and after therapy. Materials and Methods: A total of 80 de novo NHL patients, 64 with B-cell lymphomas 80%, (follicular cell lymphoma (FCL) in 32, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in 12, and diffuse large cell lymphoma in 20) and 16 with T-cell lymphomas (20%) all diagnosed as T-Lymphoblastic lymphomas, were evaluated before and after therapy. For comparison, 25 age and sex matched BM donors, were included as a control group. BMTB material and BM aspirates were taken for morphological assessment of stromal cells, the plasma of these samples being examined for $TNF{\alpha}$ and L-selectin by ELISA, and fibronectin by radial immunodiffusion (RID). Results: BM stromal cells comprising reticular macrophages and fibroblasts were elevated in 53.3% of NHL cases at diagnosis, while BM fibronectin levels were decreased and BM $TNF{\alpha}$ and L-selectin were higher than in controls (p<0.05). In NHL cases, elevated values of BM $TNF{\alpha}$ and BM L-selectin were associated with signs of aggressive disease, including >1 extra nodal sites, detectable B symptoms, high grade, BM and CNS invasion, and a high International prognostic index (IPI) (p<0.05). Conclusion: BMM components, $TNF{\alpha}$, L-selectin and fibronectin, in NHL can be useful in evaluating disease activity, extent and response to treatment and as prognostic markers according to the IPI.
Brachytherapy of Uveal Melanomas with Ruthenium-106 Plaques
Belaid, Asma;Nasr, Chiraz;Jmour, Omar;Cherif, Aziz;Kochbati, Lotfi;Bouguila, Hedi;Besbes, Mounir;Benna, Farouk 5281
Background: Brachytherapy is the most commonly used conservative treatment for the uveal melanoma. The aim of this study was to evaluate therapeutic results of Ruthenium-106 plaque brachytherapy in the management of localized uveal melanoma cases. Methods: We reviewed retrospectively the clinical records of all patients treated in our department for an uveal melanoma, undergoing Ruthenium-106 plaque brachytherapy, from January 1996 to December 2015. We focused on clinical features, therapeutic characteristics, local and distant tumor control and side effects. Results: Nineteen patients were enrolled in our study. Mean age was 56.2 years (28-79) and the sex ratio was 1.37:1 males to females. Diagnosis was made on the basis of ophthalmological clinical examination, angiography, ultrasound and/or magnetic resonance. Median tumor diameter was 9.7 mm (6-13) and median thickness 4.4 mm (2.5-8). The dose of Ruthenium-106 plaque brachytherapy prescribed to the apex of each tumor was 70 Gy in all cases. The median radiation dose to the sclera surface was 226.4 Gy (range: 179.6-342.3) and the median total application time 115.2 hours (range: 27 to 237). After a median follow-up of 61.5 months, local control was achieved in 17 patients (89%): 16 demonstrated a partial tumor response and 1 tumor stabilization. Two patients suffered local progression leading to enucleation, one dying of hepatic metastasis. Radiation-induced complications were cataracts in 3 cases and vitreal hemorrhage in 2. Conclusion: Ruthenium-106 plaque brachytherapy is an efficient treatment for localized uveal melanoma, offering good local control with low toxicity.
Does Breast Cancer Drive the Building of Survival Probability Models among States? An Assessment of Goodness of Fit for Patient Data from SEER Registries
Khan, Hafiz;Saxena, Anshul;Perisetti, Abhilash;Rafiq, Aamrin;Gabbidon, Kemesha;Mende, Sarah;Lyuksyutova, Maria;Quesada, Kandi;Blakely, Summre;Torres, Tiffany;Afesse, Mahlet 5287
Background: Breast cancer is a worldwide public health concern and is the most prevalent type of cancer in women in the United States. This study concerned the best fit of statistical probability models on the basis of survival times for nine state cancer registries: California, Connecticut, Georgia, Hawaii, Iowa, Michigan, New Mexico, Utah, and Washington. Materials and Methods: A probability random sampling method was applied to select and extract records of 2,000 breast cancer patients from the Surveillance Epidemiology and End Results (SEER) database for each of the nine state cancer registries used in this study. EasyFit software was utilized to identify the best probability models by using goodness of fit tests, and to estimate parameters for various statistical probability distributions that fit survival data. Results: Statistical analysis for the summary of statistics is reported for each of the states for the years 1973 to 2012. Kolmogorov-Smirnov, Anderson-Darling, and Chi-squared goodness of fit test values were used for survival data, the highest values of goodness of fit statistics being considered indicative of the best fit survival model for each state. Conclusions: It was found that California, Connecticut, Georgia, Iowa, New Mexico, and Washington followed the Burr probability distribution, while the Dagum probability distribution gave the best fit for Michigan and Utah, and Hawaii followed the Gamma probability distribution. These findings highlight differences between states through selected sociodemographic variables and also demonstrate probability modeling differences in breast cancer survival times. The results of this study can be used to guide healthcare providers and researchers for further investigations into social and environmental factors in order to reduce the occurrence of and mortality due to breast cancer.
Prevalence and Correlates of Physical Activity and Sitting Time in Cancer Survivors: 2009-2013 Korea National Health and Nutrition Examination Survey
Kim, Byung Hoon;Lee, Hyo 5295
Objectives: A physically active lifestyle is important for cancer survivors. Therefore, this study was conducted to 1) provide population-based estimates of the prevalence of physical activity and sitting time, and 2) their correlates in Korean cancer survivors. Materials and Methods: This study analyzed a cancer survivor subsample (N=1,482) from 2008-2013 Korea National Health and Nutrition Examination Survey (KNHANES), data selected with a complex sampling design. Overall and subgroup-specific prevalences of physical activity and sitting time were estimated. Correlates of moderate- to vigorous-intensity physical activity ( MVPA) and sitting time were tested using age-group-specific hierarchical multiple regression models. Results: Overall adherence rate to physical activity guidelines was 34.9% (95% CI=31.5-38.4). Age-group-specific adherence rates were 41.1% (95% CI=36.3-45.9) in adults (30-64 years old), and 25.3% (95% CI=21.0-25.3) in older adults (65 years or older). Adults spent 213.33 minutes (95% CI=172.4-254.3) per week on MVPA and 55.3 minutes (95% CI=36.4-64.6) on sitting time per day. In adults, sitting time was significantly associated with employed status (B=28.0, p=0.046), smoking (B=-47.4, p=0.020), and number of comorbidity conditions (B=-13, p=.037). MVPA was significantly associated with marital status (B=134.9, p<0.001), employment status (B=98.12, p=.046), and years since cancer diagnosis (B=104.7, p=0.015). Older adults spent 162.2 minutes (95% CI=119.5-204.8) per week on MVPA and 63.0 minutes (95% CI=45.0-89.5) on sitting time per day. Their significant correlates were sex (B= -45.2, p=0.014), smoking (B=-70.14, p<0.001), and years since cancer diagnosis (B=37.0, p=0.024). Age (B=5.8, p=0.042) and marital status (B=83.8, p=0.033) were also significantly associated with MVPA in older adults. Conclusion: A majority of Korean cancer survivors do not sufficiently participate in physical activity. In general, older, unhealthier, non-working, and being unmarried were risk factors for physical inactivity. While this study informs public health policy makers and practitioners about physical activity intervention demand for cancer survivors, future investigations should address psychosocial mediators to better inform intervention programs.
Genistein Suppression of Matrix Metalloproteinase 2 (MMP-2) and Vascular Endothelial Growth Factor (VEGF) Expression in Mesenchymal Stem Cell Like Cells Isolated from High and Low Grade Gliomas
Yazdani, Yasaman;Rad, Mohammad Reza Sharifi;Taghipour, Mousa;Chenari, Nooshafarin;Ghaderi, Abbas;Razmkhah, Mahboobeh 5303
Objective: Brain tumors cause great mortality and morbidity worldwide, and success rates with surgical treatment remain very low. Several recent studies have focused on introduction of novel effective medical therapeutic approaches. Genistein is a member of the isoflavonoid family which has proved to exert anticancer effects. Here we assessed the effects of genistein on the expression of MMP-2 and VEGF in low and high grade gliomas in vitro. Materials and Methods: High and low grade glioma tumor tissue samples were obtained from a total of 16 patients, washed with PBS, cut into small pieces, digested with collagenase type I and cultured in DMEM containing 10% FBS. When cells reached passage 3, they were exposed to genistein and MMP-2 and VEGF gene transcripts were determined by quantitative real time PCR (qRT-PCR). Results: Expression of MMP-2 demonstrated 580-fold reduction in expression in low grade glioma cells post treatment with genistein compared to untreated cells (P value= 0.05). In cells derived from high grade lesions, expression of MMP-2 was 2-fold lower than in controls (P value> 0.05). Genistein caused a 4.7-fold reduction in VEGF transcript in high grade glioma cells (P value> 0.05) but no effects were evident in low grade glioma cells. Conclusion. Based on the data of the present study, low grade glioma cells appear much more sensitive to genistein and this isoflavone might offer an appropriate therapeutic intervention in these patients. Further investigation of this possibility is clearly warranted.
Cost-Effectiveness of Intensive Vs. Standard Follow-Up Models for Patients with Breast Cancer in Shiraz, Iran
Hatam, Nahid;Ahmadloo, Niloofar;Vazirzadeh, Mina;Jafari, Abdossaleh;Askarian, Mehrdad 5309
Background: Breast cancer is the most common type of cancer amongst women throughout the world. Currently, there are various follow-up strategies implemented in Iran, which are usually dependent on clinic policies and agreement among the resident oncologists. Purpose: A cost-effectiveness analysis was performed to assess the cost-effectiveness of intensive follow-up versus standard models for early breast cancer patients in Iran. Materials and methods: This cross sectional study was performed with 382 patients each in the intensive and standard groups. Costs were identified and measured from a payer perspective, including direct medical outlay. To assess the effectiveness of the two follow-up models we used a decision tree along with indicators of detection of recurrence and metastasis, calculating expected costs and effectiveness for both cases; in addition, incremental cost-effectiveness ratios were determined. Results: The results of decision tree showed expected case detection rates of 0.137 and 0.018 and expected costs of US$24,494.62 and US$6,859.27, respectively, for the intensive and standard follow-up models. Tornado diagrams revealed the highest sensitivity to cost increases using the intensive follow-up model with an ICER=US$148,196.2. Conclusion: Overall, the results showed that the intensive follow-up method is not cost-effective when compared to the standard model.
Insulin-Like Growth Factors and Their Binding Proteins in Tumors and Ascites of Ovarian Cancer Patients: Association With Response To Neoadjuvant Chemotherapy
Yunusova, Natalia V;Villert, Alisa B;Spirina, Liudmila V;Frolova, Alena E;Kolomiets, Larisa A;Kondakova, Irina V 5315
Purpose: Tumor cell growth and sensitivity to chemotherapy depend on many factors, among which insulin-like growth factors (IGFs) may play important roles. The aim of the present study was to evaluate the levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in primary tumors and ascites as predictors of response to neoadjuvant chemotherapy in ovarian cancer (OC) patients. Materials and Methods: Tumor tissue samples and ascitic fluid were obtained from 59 patients with advanced OC. The levels of IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A were determined using ELISA kits. Taking into account the data on expression of these IGF-related proteins and outcome, logistic regression was performed to identify predictors of response to neoajuvant chemotherapy. Results: Human ovarian tumors expressed IGFs, IGFBP-3, IGFBP-4 and PAPP-A and these proteins were also present in ascites fluid and associated with its volume. IGFs and IGFBPs in ascites and soluble PAPP-A might play a key role in ovarian cancer progression. However, levels of proteins of the IGF system in tumors were not significant predictors of objective clinical response (oCR). Univariate analysis showed that the level of IGF-I in ascites was the only independent predictor for oCR. Conclusion: The level of IGF-I in ascites was shown to be an independent predictor of objective clinical response to chemotherapy for OC patients treated with neoadjuvant chemotherapy and debulking surgery.