فهرست مطالب

  • Volume:10 Issue: 2, 2019
  • تاریخ انتشار: 1398/01/12
  • تعداد عناوین: 12
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  • Mahshid Bagherzadeh Ansari, Ali Shahriari *, Abdolhossein Talaeizadeh, Payam Fathizadeh Pages 78-86
    Background
    A high level of replication is one of the main indicators of tumors.Tumor cells have to manufacture and transport macromolecules into daughter cells. Oneof the required enzymes is malic enzyme, which generates the NADPH for fatty acidsynthesis in order to make cell membrane and pyruvate, and support the glycolysispathway to supply the energy demand. Due to the enormous proliferation of cancer cells,it is likely that the activity of malic enzyme in cancer cells is more than normal cells.The aim of this study is to survey the kinetics of malic enzyme in tumor and normalbreast tissues.
    Methods
    We obtained the tumor and normal breast tissue specimens directlyfrom the operating room. The assays were performed with partially purified samplesunder optimum conditions for the substrate and co-factor requirements. The velocityof the enzyme or Michaelis-Menten constant, maximum velocity, and the amount ofinhibitor that reduced the enzyme activity by 50% were obtained and calculated in allsamples.
    Results
    The Michaelis-Menten constant for malate was lower in tumors comparedto normal samples. In contrast, the maximum velocity for malate in tumors was higherthan normal tissues, whereas the amount of inhibitor that reduced the enzyme activityby 50% of guanidine hydrochloride and sodium chloride were both higher in tumorsthan normal tissues.
    Conclusion
    The obtained results indicated that the malic enzyme kinetics haddifferent patterns in tumor tissues in comparison with normal tissues. A higher affinityof malic enzyme for pyruvate production in tumors supported high aerobic glycolysis.Moreover, it could be an approach to connect glutaminolysis to the glycolysis pathway.Malic enzyme could be a target to inhibit the glycolysis and glutaminolysis pathwaysin tumors.
    Keywords: Malic enzyme, Breast cancer, Kinetics, Cancer metabolism
  • Shima Hosseini, Massoud Saidijam, Hamid Eslami, Ali Reza Soltanian, Seyed Habibollah Mousavi, Bahar, Ali Mahdavinezhad * Pages 87-94
    Background
    Numerous molecular changes are involved in the development andprogression of bladder cancer. Regular follow-up of patients is crucial due to the highrecurrence rate of bladder cancer. The aim of this study is to determine the role ofB-Raf proto-oncogene, serine/threonine kinase and ZEB2 expressions in onset andprogression of bladder cancer. We have also investigated their relationships topathological characteristics.
    Methods
    We conducted this case-control study on bladder cancer and its healthyadjacent tissue, and normal bladder tissue from patients with benign prostatic hyperplasia.After extraction of total RNA and cDNA synthesis, quantitative expression analysis wasperformed in duplicate using real-time PCR. Changes in the gene expression werecalculated according to the 2(-ΔΔCt) equation. The products were confirmed by 1% agarosegel electrophoresis and sequenced by Bioneer Company. Data was analyzed using theSPSS software (version 16).
    Results
    There was significantly greater B-Raf proto-oncogene, serine/threoninekinase expression in 82% of bladder tumor samples compared to the adjacent tissues.In 91.1% of tumor samples, the gene expression was also significantly higher than healthybladder tissues from patients with benign prostatic hyperplasia. We observedoverexpression of B-Raf proto-oncogene, serine/threonine kinase in 61.7% of thehealthy margin tissue samples compared to healthy bladder tissues of patients with benignprostatic hyperplasia (P<0.001). Expression of ZEB2 in 52.9% of the bladder tumorsamples was significantly higher than healthy peripheral tissues. This increase wasobserved in 94.1% of tumor samples compared to healthy bladder tissues of patientswith benign prostatic hyperplasia (P<0.001). Pearson correlation coefficient showeda positive relationship between B-Raf proto-oncogene, serine/threonine kinase and ZEB2in cancerous samples (r = 0.75) and healthy margin tissue samples (r = 0.49).
    Conclusion
    During the carcinogenesis process, molecular changes are seen inhealthy margin tissue. These molecular changes may be the reason for the highrecurrence rate of bladder cancer. B-Raf proto-oncogene, serine/threonine kinase canpotentially be a target cancer therapy in antisense technologies.
    Keywords: Biomarkers, BRAF, ZEB2, Urinary bladder neoplasm
  • Fatemeh Sari Aslani, Akbar Safaei, Hale Ghezelbash, Mozhdeh Sepaskhah * Pages 95-102
    Background
    The lack of a specific marker to differentiate malignant from reactiveT-cells makes a definite diagnosis difficult in patients suspected of having mycosisfungoides. This study has evaluated value of thymocyte selection-associated highmobility group box factor expression in the differentiation of early mycosis fungoidesfrom a benign inflammatory dermatosis.
    Methods
    We selected 22 mycosis fungoides cases, 18 cases suspicious for mycosisfungoides, and 12 cases of eczematous dermatitis from patients who attendedDermatology Clinic, Shiraz University of Medical Sciences (2008-2015). The obtainedskin biopsies were immunostained for thymocyte selection-associated high mobilitygroup box factor antigen in addition to pan T cell markers. The slides were evaluatedfor the percentage of tumor cells and intensity of immunoreactivity.
    Results
    From 22 cases of mycosis fungoides, 40.9% showed massive infiltrationof thymocyte selection-associated high mobility group box factor-positive lymphocytes(>30%) with high (3+) intensity in the epidermis; there was no case negative forthymocyte selection-associated high mobility group box factor expression. Only oneeczematous dermatitis case had expression of thymocyte selection-associated highmobility group box factor-positive lymphocytes (>30%) with high intensity and 4 caseswere negative for thymocyte selection-associated high mobility group box factorexpression. The frequency of thymocyte selection-associated high mobility groupbox factor expressing lymphocytes was higher in biopsies from mycosis fungoidescompared to eczematous dermatitis (P<0.05). CD7- cases expressed more thymocyteselection-associated high mobility group box factor-positive lymphocytes in the dermisand epidermis, which were significantly correlated (P=0.013).
    Conclusion
    Thymocyte selection-associated high mobility group box factor, as apositive marker, in combination with pan T cell markers (especially CD7-) can be usefulto detect mycosis fungoides malignant lymphoid cells.
    Keywords: MF, TOX Immunoexpression, T cell markers, CD7-
  • Arnadi Shivashankara, Raees Tonse, Sucharitha Suresh, Thomas George, Mamidipudi Vidyasagar, Suresh Rao, Manjeshwar Baliga * Pages 103-110
    Background
    In this study, we sought to understand the usefulness of salivary lactatedehydrogenase as a predictive marker for the development of radiation-inducedmucositis.
    Methods
    This was a prospective study with head and neck cancer patients whorequired curative radiotherapy (>60Gy). We collected patients’ saliva before the onsetof radiation and after 2 Gy of radiation to assess lactate dehydrogenase levels. The patientsreceived the stipulated oral and dental care. Data on incidence and severity of mucositiswas collected using a preform sheet and oral mucositis assessment scale published bythe Radiation Therapy Oncology Group throughout the 7-week treatment period.
    Results
    Salivary lactate dehydrogenase increased with exposure to radiation(P<0.0001) and there was an observed association with mucositis severity (P<0.0001;r = 0.515).
    Conclusion
    The present results have established, for the first time, that salivarylactate dehydrogenase could be a useful predictive marker to understand the developmentof radiation-induced mucositis in patients with head and neck cancer. The proximityof the oral cavity for regular observation and saliva collection is an added advantage.
    Keywords: Head, Neck Cancer, Salivary lactate dehydrogenase, Mucositis
  • Faezeh Sadrabadi Haghighi, Mohsen Aliakbarian, Alireza Khooei, Seyed Isaac Hashemy * Pages 111-117
    Background
    Thioredoxin, NADPH, and thioredoxin reductase form the thioredoxinsystem which exists in all living cells. Oxidants have a major role in cancer pathogenesis;therefore, it is necessary to study the role of redox-active compounds such as thioredoxinreductase to increase our knowledge about the molecular mechanisms involved in cancerpathogenesis and ultimately design more effective treatments. The research on the roleof the thioredoxin system in pancreatic cancer is limited; hence, we intend to comparethe tissue distribution and activity of thioredoxin reductase in pancreatic cancer withhealthy tissues located at the tumor margins.
    Methods
    A total of 29 patients with pancreatic cancer participated in this study.The tissue distribution was determined by immunohistochemistry analysis. We useda commercial ELISA kit to determine enzyme activity.
    Results
    There was no significant difference between the tumor tissue and itsnormal surrounding tissue in terms of thioredoxin reductase activity (P=0.56). However,there was a significant difference when we considered the different disease stages. Asignificant relationship also existed between the staining intensity of thioredoxinreductase and disease stage (P=0.022).
    Conclusion
    There was no observed difference between the pancreatic cancertissue and its healthy margin in terms of thioredoxin reductase activity and tissuedistribution. This finding did not support its possible role in pancreatic cancerpathogenesis.
    Keywords: Oxidative stress, Thioredoxin reductase, Pancreatic cancer, Immunohistochemistry, Antioxidant
  • Mohammad Javad Khezeli, Mehdi Dehghani, Khosro Keshavarz, Zahra Kavosi * Pages 118-124
    Background
    Cancer is one of the major causes of mortality and as an effectivefactor in the burden of diseases for the future. Among all cancers, gastric cancer is thefourth most common and the second leading cause of cancer mortality worldwide. Inthis study, we aim to evaluate the cost-utility of two chemotherapy regimens –epirubicin, oxaliplatin, and capecitabine versus docetaxel, cisplatin, and fluorouracilin patients with advanced gastric cancer in a hospital in southern Iran.
    Method
    This cross-sectional study was an economic evaluation of cost-utility typethat included all patients at Amir Hospital (Shiraz, Iran) who had advanced gastric cancerand received either the epirubicin, oxaliplatin, and capecitabine or docetaxel, cisplatin,and fluorouracil chemotherapy regimen. All costs and the quality-adjusted life yearswere calculated, followed by one-way sensitivity analysis to verify the results.
    Results
    A total of 54 patients participated in this study, amongst whom 20 receivedthe epirubicin, oxaliplatin, and capecitabine regimen and 34 received the docetaxel,cisplatin, and fluorouracil regimen. The mean quality of life of patients that receiveddocetaxel, cisplatin, and fluorouracil was 0.747, whereas it was 0.836 for patients thatreceived epirubicin, oxaliplatin, and capecitabine. The docetaxel, cisplatin, andfluorouracil treatment group ($5573) was more expensive than the epirubicin, oxaliplatin,and capecitabine group ($3108). The results obtained from the cost-utility analysisshowed that the epirubicin, oxaliplatin, and capecitabine drug regimen was costeffectivedue to lower cost and higher utility than the docetaxel, cisplatin, andfluorouracil regimen. One-way sensitivity analysis confirmed the accuracy of theseresults.
    Conclusion
    Due to the cost-effectiveness of the epirubicin, oxaliplatin, andcapecitabine drug regimen compared to docetaxel, cisplatin, and fluorouracil, werecommend that oncologists use this regimen to treat gastric cancer patients.
    Keywords: Cost-utility, EOX, DCF, Gastric Cancer
  • Abeer Anter *, Rasha AbdelLatif Pages 125-131
    Background
    Desmoid tumors are rare soft tissue neoplasms that have a variable and often unpredictable clinical course. We have conducted a phase II study to evaluate the efficacy and safety of tamoxifen and sulindac in treatment of primary unresectable and recurrent desmoid tumors.
    Methods
    Eligible patients were ≥18 years of age who had measurable histologically confirmed recurrent or newly diagnosed tumors not amenable to R0 resection, or those who underwent tumor excision with gross residual desmoid tumor. The primary objective was to estimate progression-free survival. Patients received 20 mg tamoxifen and 300 mg sulindac daily for up to 12 months according to absence of disease progression or unacceptable drug toxicity.
    Results
    25 patients, 12 males and 13 females, whose ages ranged from 18-60 years. Most (88%) had a good performance status (ECOG 1). A total of 6 of 15 patients with recurrent desmoid tumors had histories of prior local radiotherapy for their primary tumors. There were 10 newly diagnosed patients, 15 (60%) had recurrent disease and only one patient had a diagnosis of familial adenomatous polyposis. Only 22 patients completed the treatment protocol and were evaluated for clinical response and time to progression. All patients were evaluated for safety profile. The overall response rate was 60%, with complete response observed in 8% and partial response in 52%. At two years, the estimated progression-free survival rate was 55% with a median progressionfree survival of 25 months.
    Conclusion
    According to the results of this study, systemic treatment with tamoxifen and nonsteroidal anti-inflammatory drugs is safe and effective in patients with desmoid tumors.
    Keywords: Desmoid tumor, Sulindac, Tamoxifen
  • Mehdi Nourelahi, Ali Zamani *, Abdolrasoul Talei, Sedigheh Tahmasebi Pages 132-138
    Background
    Breast cancer is the most common type of cancer amongst women worldwide. Considering its high incidence, effective detection and prognosis of this type of cancer may have a significant effect on reducing expenditures. In this study, we propose a model to predict the 60-month survivability in patients with breast cancer and investigate the effects of each feature on the obtained model.
    Methods
    We base this model on the information gathered by the Breast Disease Research Center, Shiraz University of Medical Sciences, Shiraz, Iran from 5673 patients with breast cancer. The goal of this study was to predict breast cancer survivability at early diagnosis, so the features used in the research are among those considered affordable, specifically at the initial steps of diagnosis. After preprocessing all of the cases and features, we constructed this model based on 1930 cases and 16 of their associated features using logistic regression method. The model then was evaluated with 10-fold cross validation.
    Results
    Based on all subsets of the 16 features, we evaluated numerous models. We selected a model that achieved the best sensitivity and specificity, and used fewer features as the best model. We considered this model for further analysis, which is consisted of following features: age at the time of diagnosis, type of invasion, HER2, size of the tumor, in situ component, lymph node involvement ratio, progesterone receptor status, and the total number of dissected lymph nodes. The best model obtained overall accuracy, specificity and sensitivity of 72.49%, 72.83%, and 71.85%, respectively.
    Conclusion
    The performance of model is quite satisfactory due to the fact that we only used features, which could be obtained at the initial steps of diagnosis. Even though, the effect of patient’s age is controversial, we concluded that ageing would decrease the 60-month survivability. Our model indicated that having all type of invasions (i.e. vascular, lymphatic, etc.) would result in poorer chance of survival compared to other features effect.
    Keywords: Statistical learning, Data mining, Breast cancer, Logistic regression, Survivability
  • Mohammad Javad Foroughi Moghadam, Mohsen Ayati, Maryam Rangchian, Gholamreza Pourmand, Peiman Haddad, Alireza Nikoofar, Hamidreza Rezvani, Seyed Jalil Hosseini, Jamshid Salamzadeh, Hamid Reza Rasekh * Pages 139-155
    Background
    Prostate cancer (PCa) is the third most diagnosed cancer among men in Iran with approximately 4200 new cases in 2015. Considering the rapid growth of cancer diagnosis, this study aims to investigate the economic burden of PCa patients and their health-related quality of life (HRQoL)
    Methods
    A retrospective survey was conducted on 500 registered patients to discover the pattern of care and distribution of patients in the main treatment categories. In the next step, a multi-center survey of the patients under treatment was conducted. The objective of this survey was to estimate direct medical costs (DMC), non-medical costs, and productivity losses for patients and family members. HRQoL was measured by the Functional Assessment of Cancer Therapy–Prostate questionnaire.
    Results
    Despite high age of patients (72±9.25 years), only 53.3% of them were retired or disabled. The largest proportion of patients (54.3%) received medicinal or surgical hormone therapy. Radical prostatectomy was the main treatment for 31.7% of patients, 10.2% received radiation therapy, and 3.8% underwent chemotherapy. DMC for incident population was approximately 12.5 million US dollars/year, and the highest average cost per capita belonged to chemotherapy patients. Unpredictably, productivity loss was nearly as much as direct cost. The mean score for HRQoL was 0.62±0.16 for all patients. Orchiectomy group had the lowest HRQoL score (0.55±0.16). Chemotherapy patients suffered the worst scores in the physical well-being subscale (0.47±0.24). Hormone therapy patients had the least scores in the prostate-specific subscale (0.50±0.18).
    Conclusion
    The economic burden of PCa is estimated approximately 25.8 million US dollars per year for incident population. When we refer to the high proportion of patients diagnosed in advanced state of the disease and higher per capita cost for these patients, policy makers should promote screening strategies to control health care costs and to increase both life expectancy and HRQoL.
    Keywords: Cost of illness, Societal perspective, Productivity loss, Health-related quality of life, FACT-P
  • Minoo Robati *, Marjan Hosseini, Maryam Zolghadr, Mojdeh Momtahan, Fatemeh Sadat Najib Pages 156-159
    Chronic non-puerperal uterine inversion is a rare condition that usually presents with vaginal bleeding and vaginal mass. Frequently, it is caused by benign and malignant tumors. A mass in the vagina, particularly if it is a malignant tumor, can be confused with a uterine malignancy without inversion. Clinical diagnosis of chronic uterine inversion is difficult and may be diagnosed during surgery. In this report, we present a case of chronic uterine inversion diagnosed as a uterine sarcoma by punch biopsy.
    Keywords: Chronic uterine inversion, Sarcoma
  • Sohaila Fatima *, Wajih Siddiqui, Abdulrahman Alshehri Pages 160-164
    Anaplastic large-cell lymphoma is an aggressive non-Hodgkin lymphoma of T cell/null cell origin. It rarely affects the gastrointestinal tract. We present the case of a 58-year-old patient diagnosed with anaplastic lymphoma of the stomach in association with Kaposi’s sarcoma of the skin.
    Keywords: Anaplastic lymphoma, Stomach, Kaposi’s sarcoma
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