Tehran University Medical Journal

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Background: Hypopharyngeal cancer usually presents with cervical mass, hoarseness, radiated otalgia, and dysphagea in the advanced stages. Radical surgery followed by radiotherapy plays an important role in the treatment of patients with hypopharyngeal cancer. However, there is no general consensus as to which is the best method of reconstruction after surgical resection. The aim of this study was to evaluate the complications of pectoralis major myocutaneous flap (PMMF) and gastric pull-up (GPU) techniques to reconstruct a circumferential defect after laryngopharyngoeso- phagectomy.

Methods: We retrospectively reviewed the records of 64 patients who underwent radical surgery and reconstruction with either PMMF or GPU technique. Demographic characteristics, tumor location, proximal margin involvement, history of radiotherapy, presence of lymphadenopathy, cervical dissection, and postoperative complications such as fistula, anastomotic site stenosis, swallowing dysfunction, and stoma stenosis were compared between the two groups. Postoperative complications of the reconstruction methods were compared.

Results: A total of 64 patients, 43(67%) in GPU group and 21(33%) in PMMF group, were studied. The groups did not differ in demographic characteristics. The locations of the tumoral lesions were in larynx (n=7), proximal esophagus (n=5), posterior cricoid (n=5), pyriformis sinus (n=7), posterior wall (n=7), and miscellaneous (n=41). Six patients (6.3%) had proximal margin involvement, 19 patients (29.9%) had history of radiotherapy, 26 cases (40.6%) had lymphadenopathy, and 49 cases (76.5%) had cervical dissection. There was no significant difference between the two groups regarding stenosis or swallowing dysfunction rates, but fistula was seen lower following GPU compared with PMMF (p<0.001).

Conclusions: The GPU technique results in similar functional stenosis or swallowing dysfunction rates, but lower fistula compared with PMMF reconstruction.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 !mso]> ject classid="clsid:38481807-CA0E-42D2-BF39-B33AF135CC4D" id=ieooui> Background: Ovarian cancer is the leading cause of death among all gynecologic cancers in developed countries. The standard treatment for advanced ovarian cancer consists of cytoreductive surgery associated with a platinum/paclitaxel-based chemotherapy. Over than 50% of patients with advanced ovarian cancer will develop recurrent disease. For those patients who have recurrence of disease at least six months after initial therapy, the paclitaxel- platinum combination has been shown to be a superior treatment to platinum monotherapy. However, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. The efficacy and safety of an alternative regimen that dose not show significant neurotoxicity were evaluated by comparing gemcitabin- carboplatin with carboplatin in platinum sensitive recurrent ovarian cancer patients in a Gynecologic Cancer InterGroup trial in Canada and European Organization for research and treatment of Cancer Gynecological Cancer Group. But this study was not done in Iran.
Methods: We performed a study with escalating doses of gemcitabin combined with carboplatin in 21 patients. All patients who were treated in Vali-Asr hospital between 2003- 2005 evaluated. Gemcitabin with dose of 800mg/m² was given on days 1, 8 and 15 followed by one week rest period for a 28 day cycle. Combine with carboplatin with AUC 4 given on day 2. All patients with surgically resected, histologically confirmed epithelial ovarian cancer and who had failed first- line platinum chemotherapy were allocated to this study.
Results: Median age was 49 years (range 23-78 years). Median follow-up was six months (range 4-22). Total of 87 cycles of chemotherapy were administered with median number of four (range 2-6 cycles). Thrombocytopenia (grade I) and leucopenia (grade I) were seen in 4.75% and 9.52% of patients.
Conclusion: Gemcitabin and carboplatin Combination was tolerated in patients with recurrence of ovarian cancer.

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Background: Chemo-radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay or interruption of treatment plan, cyclo-oxygenase 2 (COX2) is an inducible enzyme primarily expressed in inflamed and tumoral tissues. COX-2 inhibitors have shown promise to reduce chemoradiation induce toxicities. We conducted a phase III, randomized double blind clinical trial to evaluate the toxicity and efficacy of celecoxib, a selective COX2 inhibitor, administered concurrently with chemoradiation for locally advanced head and neck cancer. Here in we report the first report about the role of COX-2 inhibitor in acute toxicicities.

Methods: Patients with stage III/IV (locally advance) head and neck carcinoma who referred to department of radiation-oncology were eligible. Patients were treated with chemotherapy with cisplatin concurrently with radiation (60-70Gy). Celecoxib (100mg qid) was started at the first day of radiotherapy and was given for a total of 8 weeks. Acute toxicities were evaluated every week by WHO scale.

Results: One hundred twenty two patients were enrolled into the study, (61 patients for each group). In repeated mesurment analysis of variance there is a significant difference in the time of onset of grade II acute toxicities between the two groups The mucositis, dysphagia, epidermitis and oral pain score changed significantly over the typical five weeks in two groups but these changes were more sever in placebo group (p=0.0001). In the analysis of the overall changes in the following laboratory parame-ters: WBC, hemoglobin and platelet showed that these parameters decreased over time in both groups without a significant difference between groups.

Conclusion: The results of these study showed that the use of a COX-2 inhibitor (celecoxib) that is a safe and inexpensive drug may reduce acute toxicities of chemoradiation specially mucositis in head and neck carcinoma.

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The prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer), and also the second leading cause of cancer death (after lung cancer) among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes. The family history is an important risk factor for developing the disease. The genes AR, CYP17, SRD5A2, HSD3B1 and HSD3B2 are all intimately involved in androgen metabolism and cell proliferation in the prostate. Each shows intraspecific polymorphism and variation among racial-ethnic groups that is associated with the risk of prostate cancer. Some of genes expressed in the prostate are in association with the production of seminal fluid and also with prostate cancer. Epigenetic modifications, specifically DNA hypermethylation, are believed to play an important role in the down-regulation of genes important for protection against prostate cancer. In prostate cancer numerous molecular and genetic aberrations have been described. It is now well established that cancer cells exhibit a number of genetic defects in apoptotic pathways. In this review article, the most recent data in molecular genetic, prevention and especially gene therapy in prostate cancer are introduced.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Gastric cancer is the second most common cancer and known as the second cause of death due to cancers worldwide. Adenocarcinoma is the most fatal cancer in Iran and a patient with this kind of cancer, has a lower lifetime than others. In this research, the survival of patients with gastric carcinoma who were registered at Taleghani Hospital, were studied.
Methods:  291 patients with Gastric carcinoma who had received care, chemotherapy or chemoradiotherapy, at Taleghani Hospital in Tehran from 2002 to 2007 were studied as a historical cohort. Their survival rates and its relationship with 12 risk factors were assessed.
Results:  Of the 291 patients with Gastric carcinoma, 70.1 percent were men and others (29.9%) were women. The mean age of men was 62.26 years and of women was 59.32 years at the time of diagnosis. Most of patients (93.91%) were advanced stage and metastasis. The Cox proportional hazards model showed that age at diagnosis, tumor stage and histology type with survival time had significant relationships (p=0.039, p=0.042 and p=0.032 respectively).
Conclusion: The five-year survival rate and median lifetime of gastric cancer patients who underwent chemotherapy or chemoradiotherapy are very low and seems that one of the important reasons for this situation is delayed diagnosis. The scheme of public education about the early warning signs of the disease and diagnosis and administration of periodic examinations is unavoidable.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Seroma formation, or the subcutaneous collection of fluid, is a common problem after surgery for the breast cancer. It may lead to wound-related complications and also can delay adjuvant therapy. The aim of this study was to investigate the effect of various clinical and therapeutic variables on seroma formation.
Methods: A prospective cross sectional study of patients who underwent surgical therapy for breast cancer was carried out. Modified radical mastectomy was performed on 67 patients (65%) and 28 patients (27.2%) underwent breast conservative surgery. Simple extended mastectomy was done for the remaining 8 patients (7.8%). Seroma formation was studied in relation to age, type of surgery, tumor size, nodal involvement, preoperative chemotherapy, surgical instrument (electrocautery or scalpel), use of pressure garment, and duration of drainage. All of the patients followed for 4 weeks after surgery.
Results:  A total of 103 patients with breast cancer were studied. The mean age of the patients was 48.3 years (25-82). Seroma occurred in 27 (26.2%) patients. There was statistically significant relation between age and seroma formation after breast cancer surgery (p=0.005), while other factors studied was found to be significantly ineffective. In addition, there was not any relation between seroma formation and drain duration. However, two factors including type of the operation and level of lymphatic dissection was considerable with confidence interval up to 90%, but it was not statistically significant with confidence interval >95% (p=0.068 and 0.063 respectively).
Conclusion: These findings suggest that the age is a predicting factor for seroma formation in breast cancer patients, while other factors do not significantly affect that.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Detection rate of Ductal Carcinoma Insitu of the breast (DCIS) have increased rapidly over the past decade, which is generally attributed to the widespread use of screening mammography. The aim of this study was to evaluate the prevalence of ductal carcinoma in situ in patients who had been referred to Tehran university medical centers.
Methods: In a retrospective study, medical records of the patients with diagnosis of breast cancer in 3 teaching hospitals of Tehran University of Medical Sciences (Cancer Institute, Sina and Shariati Hospitals between 1994-2003) were reviewed and records with ductal carcinoma in situ were selected and analyzed.
Results: Between 2244 medical records of breast cancer 23 patients had DCIS (1.02%). Mean age was 47.3 years just one patient had been detected by screening mammography and others had clinical symptoms. 48% of patients had mass with mean size of 3.3cm. All had undergone open biopsy (four incisional, 19 excisional). Treatment included 65.2% modified radical mastectomy, 30.4% lumpectomy with axillary dissections and 3.8% lumpectomy alone. Nine patients had radiotherapy after surgery and ten took tamoxifen as hormonal therapy. Two patients (8.6%) in lumpectomy group had recurrence in follow ups. Median follow up time was 84 months.
Conclusion: This study shows that the Prevalence of early stages of breast cancer especially ductal carcinoma in situ is extremely low. (DCIS was 1.02 in comparison with 15-30% in western countries). These findings indicate the need for increasing public information about breast cancer in Iran and improving screening programs of breast cancer.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Breast conservative therapy is associated with similar outcomes in comparison with mastectomy. The aim of this study is assessment of local recurrence rate and related risk factors in patients who have been treated with radiotherapy after conservative surgery for breast cancer.

Methods: This is a cohort study which data of all breast cancer patients who have visited in follow up clinic in radiation oncology department of cancer institute of Imam Khomeini Hospital complex in Tehran, Iran, during years 2007-2009 were collected. All of the patients were investigated for local recurrence and the possible risk factors.

Results: Two hundred and seventy seven patients have entered the study and all have followed for at least one year since data entry. Median follow-up time from the start of radiotherapy were 35 months (12-148 mo). We had seven cases (2.5%) with local recurrences (2.5%) which most of them occurred in first year after treatment. Because of low rate of recurrence none of the variables such as margin and nodal status has significant correlation with local recurrence which this should be due to small number of patient and short time of follow up.

Conclusions: At median follow up of 35 months from the beginning of radiation therapy, local recurrence rate was 2.5% which is similar to the literature. We recommend to follow a larger group of patients for longer times to estimate recurrence risk after breast conservative therapy.

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Background: Inhibin is a dimeric glycoprotein that has a depressive effect on the anterior hypophys secretion. The level of this tumor marker is undetectable in menopause women. In patients with gynecological cancer, especially granulosa and epidermal-type (mucinous), ovarian cancers considerable increase in the serum level of inhibin has been reported. The increased level of inhibin has been reported in patients with recurrent ovarian cancer. Methods: We measured total serum inhibin and CA125 tumor marker level in 38 postmenopausal women with pathologically confirmed ovarian cancer before and after surgery out of 51 suspected women. Our control group were postmenopausal women that attended to our clinic for routine gynecologic check up. Both tumor markers were measured in these patients too. Results: Among 38 women with ovarian cancer, 13(34.2%) had elevated serum levels of total inhibin. Among the 16 women with serous adenocarcinoma, 3 patients (18.8%) had elevated serum levels of inhibin. All the three women with granulosa cell tumor had elevated serum levels of inhibin (100%) and 3 of 4(75%) women with mucinous ovarian cancer had the same result. three out of 38 women in control group had elevated serum levels of inhibin. Among all 38 patients, 6(15.7%) showed tumor recurrence, that all were concomitant with rising of both serum CA125 and Inhibin levels (p=0/001). Conclusions: Serum inhibin level is a usefull tumor marker in granulosa cell and in mucinous tumor of ovary. In this study combined inhibin and CA125 assay showed better results in early detection of ovarian cancer in comparison to either CA125 or inhibin alone

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Background: Fever in neutropenic patients is a medical emergency which may happen in patients undergoing chemotherapy. The definition of neutropenia varies from institution to institution but is usually defined as an absolute neutrophil count (ANC) < 500 cells/l or < 1,000 cells/l with a predicted nadir of < 500 cells/l. Bacterial and fungal infections are the most important in neutropenic patients. Viral infections with agents such as herpes simplex virus and cytomegalovirus are common but less than other pathogens. Case presentation: We report a patient with fever & neutropenia following cytomegalovirus infection during chemotherapy course for breast cancer. Conclusion: Although fever and neutropenia after cytomegalovirus infection is not very common but prompt diagnosis and treatment of this disease reduces the mortality and morbidity associated with cytomegalovirus. For this reason, screen testing for CMV infection in high risk patients including patients with cancer and preemptive therapy in patients with viremia, for prevention of CMV disease could be considered as a strategy for prevention of CMV infection.

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Background: Esophageal cancer is one of the most lethal diseases in the world. It has a high prevalence in Iran, especially in the Northern provinces. The main treatment of esophageal cancer is surgery. There are two common surgical procedures for its treatment, Transhiatal esophagectomy and transthoracic esophagectomy. The aim of this study was to compare the results of above methods in esophageal cancer. Methods: This cross-sectional study was done on patients with pathologic diagnosis of esophageal cancer that referred to surgery ward of Shahid Beheshti Hospital, in Babol, Iran in 2002-2008. Patients according to the location of tumor and physical status were undergone transhiatal or transthoracic esophagectomy. Demographic and surgical findings were recorded. The patients were matched according to age, sex, weight loss, serum albumin level and hemoglobin concentration in two groups. Results: Fifty nine percent of patients were under transhiatal esophagectomy and 41% were under transthoracic esophagectomy (n=166). Morbidity did not show significant difference (p=0.636) between transhiatal (42.9%) and transthoracic (47.1%) methods. Duration of surgery (min) in transhiatal method (180.7±35.1) was significantly (p<0.0001) lower than the transthoracic one (226.7±54.2). Duration of admission (days) did not show significant difference (p=0.44) between transhiatal esophagectomy (8±4.9) and the other method (8.5±1.6). Mortality in 30 days after surgery did not show significant difference (p=0.489) between two groups (4.1% against 7.4%). Conclusions: Based on our study, duration of surgery in transhiatal esophagectomy was lower than transthoracic method. Other parameters include morbidity, mortality, and duration of admission had not significant difference between two groups.

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Background: Colorectal cancer is the third common cancer world wide and the forth in Iran. Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. In this study we evaluate the efficacy a cox-2 inhibitor on pathologic response, sphincter preservation and acute toxicity during neoadjuvant chemoradiation.

Methods: Thirty-six patients that have adenocarcinoma of rectum was enrolled (up to 15 cm of anal verge). The patients were undergone Endometrial Ultrasound (EUS), abdomino-pelvic and chest CT for staging. Then received neoadjuvant concurrent chemo radiation (xeloda 825 mg/m2 bid in combination with celecoxib 100 mg qid and 50-50.4Gy/25-28f). Surgery was done 4-8 weeks after chemoradiation. During the chemoradiation the patients was observed for the probable complication one year. Tumor regression grade was reported.

Results: From 36 surgery patients, Total Mesorectal Excision (TME) was done in 30 patients. Pathologic complete response was seen in eight of 30 patients (26.7%). Tumor regression grade was calculated in three and five grade system: in three grade system 17 patients had grade 1 (60.7%), eight patients had grade 2 (28.6%) and three patients had grade 3 (10.7%). In five grade system of tumor regression eight patients had grade 1 (28.6%), nine patients had grade 2 (32.1%), eight patients grade 3 (28.6%), three patients had grade 4 (10.7%). T down staging was 43.3%. N downstaging was 30.8%. No patient had skin reaction or cardio-vascular complication.

Conclusion: Based on our study results, Celecoxib in combination with neoadjuvant chemoradiation is safe and is associated with low complications. This combination can promote pathologic complete response, TRG and T and N downstaging in Rectal adenocarcinoma.

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Background: Based on the reports, high frequency of special alleles of HLA class II genes might be associated with susceptibility to or protective from a particular cancer. These alleles might vary depending on the geographical region. Here we investigate the association between alleles of HLA class II genes and breast cancer in Iranian women.
Methods: 100 patients with pathologically proved breast cancer who referred to Cancer Institute, Tehran University of Medical Sciences in Tehran, Iran, were divided to two groups based on ages (40 years old and less/ or more than 40 years old) and were randomly selected and compared with a group of 80 healthy blood donor subjects. HLA class II alleles were determined by amplification of DNA with polymerase chain reaction (PCR) method followed by HLA-typing using sequence-specific primer (SSP) for each allele.
Results: The most frequent alleles in the DR and DQ regions in group 1 (40 years old and less) in comparison with control group were HLA-DQA1*0301 (p=0.002) and HLA-DQB1*0302 (p>0.05). In contrast HLA-DQA1*0505 (p=0.004) had significantly lower frequency in this group compared with control group. Patients of group two (more than 40 years old) had a higher frequencies of HLA-DQA1*0301 (p=0.001) and HLA-DRB1*1303 (p=0.02) and a lower frequency of HLA-DQA1*0101 (p=0.002) compared to healthy control.
Conclusion: These findings provide information of a positive and negative association between certain alleles of HLA class II and breast cancer in our population and also might support that the pattern of inheritance in the early and late onset of breast cancer differ substantially.

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Background: The current standard of adjuvant management for gastric cancer after curative resection based on the results of intergroup 0116 is concurrent chemoradiation. Current guidelines for designing these challenging fields still include two-dimensional simulation with simple AP-PA parallel opposed design. However, the implementation of radiotherapy (RT) remains a concern. Our objective was to compare three-dimensional (3D) techniques to the more commonly used AP-PA technique.
Methods: A total of 24 patients with stages II-IV adenocarcinoma of the stomach were treated with adjuvant postoperative chemoradiation with simple AP-PA technique, using Cobalt-60. Total radiation dose was 50.4Gy. Landmark-based fields were simulated to assess PTV coverage. For each patient, three additional radiotherapy treatment plans were generated using three-dimensional (3D) technique. The four treatment plans were then compared for target volume coverage and dose to normal tissues (liver, spinal cord, kidneys) using dose volume histogram (DVH) analysis.
Results: The three-dimensional planning techniques provided 10% superior PTV coverage compared to conventional AP-PA fields (p<0.001). Comparative DVHs for the right kidney, left kidney and spinal cord demonstrate lower radiation doses using the 3D planning techniques (p<0.0001), the liver dose is higher (p=0.03), but is still well below liver tolerance.
Conclusion: Despite the department protocol using conventional planning, 3D radiotherapy provides 10% superior PTV coverage. It is associated with reduced radiation doses to the kidneys and spinal cord compared to AP-PA techniques with the potential to reduce treatment toxicity.

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Background: Reconstruction by free tissue transfer and microvascular anastomosis can provide a reliable repair for tissue defects in head and neck surgeries. During this study, we evaluated the clinical characteristics and outcomes of reconstructive surgery by the use of free flaps for defects resulting from head and neck cancers. Methods: This quasi-experimental study included 29 patients having been diagnosed with head and neck cancers and referred to the Plastic Surgery Clinic and Cancer Institute of Imam Khomeini Hospital Complex in Tehran, Iran, for the resection of cancerous tissue. After operation, the patients were followed-up for three months and the surgical outcomes were evaluated. Results: The mean age of participants was 50.8 ± 15.1 yrs. Two patients (6.9%) had total and three (10.3%) had partial flap loss. The rate of total and partial flap loss in this study was less than 10%. There were no differences between groups with total and partial flap loss regarding mean age, mean operation time, and mean perioperative ischemia time. Prothrombin time (PT) and international normalized ratio (INR) were significantly different in patients with total flap loss compared with patients with successful reconstruction. The INR for the group with total loss was 2.2 and 1.2 ± 0.3 for other patients (P=0.0006). The mean ACT was 46 seconds in patients with total flap loss and 82 ± 18.9 seconds for other patients (P=0.08). Conclusion: Considering its high success rate, free tissue transfer can be considered as a method for single-stage reconstruction in almost all major head and neck defects.

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Background: With approximately 386,000 deaths per year, esophageal cancer is the 6th most common cause of death due to cancer in the world. This cancer, like any other cancer, is the outcome of genetic alterations or environmental factors such as tobacco smoke and gastro-esophageal reflux. Tobacco smoking is a major etiologic factor for esophageal squamous cell carcinoma in western countries, and it increases the risk by approximately 3 to 5 folds. Chronic gastro-esophageal reflux usually leads to the replacement of squamous mucosa by intestinal-type Barrett’s metaplastic mucosa which is considered the most important factor causing esophageal adenocarcinoma. In contrast to esophageal adenocarcinoma, different risk factors and mechanisms, such as mutations in oncogenes and tumor suppressor genes, play an important role in causing esophageal squamous cell carcinoma. Molecular studies on esophageal cancers have revealed frequent genetic abnormalities in esophageal squamous cell carcinoma and adenocarcinoma, including altered expression of p53, p16, cyclin D1, EGFR, E-cadherin, COX-2, iNOS, RARs, Rb, hTERT, p21, APC, c-MYC, VEGF, TGT-α and NF-κB. Many studies have focused on the role of different polymorphisms such as aldehyde dehydrogenase 2 and alcohol dehydrogenase 2 in causing esophageal cancer. Different agents including bestatin, curcumin, black raspberries, 5-lipoxygenase (LOX) and COX-2 inhibitors have been found to play a role in inhibiting esophageal carcinogenesis. Different gene therapy approaches including p53 and p21WAF1 replacement gene therapies and therapy by suicide genes have also been experimented. Moreover, efforts have been made to use nanotechnology and aptamer technology in this regard.

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Background: Human cancer cell lines express human choriogonadotropin (hCG), its subunits and derivatives, regardless of their origin and type. It appears that hCG is a common phenotype in human cancer cell lines. In this research, the effects of hCG targeting monoclonal antibodies (7D9, T18H7 and T8B12) on human cancer cell lines were evaluated.
Methods:  Monoclonal antibody secreting hybridomas were proliferated and injected intraperitoneally to Balb/C mice after treatment with pristine. Two weeks later, ascites fluid was collected. Purification of aforementioned antibodies from ascites fluid was performed using G-protein affinity followed by ion exchange chromatography. SDS-PAGE and ELISA confirmed the structure and functional integrity of the purified antibodies, respectively. Two human cancer cell lines "Hela" and "MDA" were treated by the purified antibodies. Three days later, different wells were imaged and the cells counted.
Results:  SDS-PAGE gel (None-reducing) indicated consistency of band migration patterns with control antibodies. ELISA test using hCG antigens indicated that the produced antibodies could detect hCG antigens. Cell lines were cultured and treated with different concentrations of each antibody. Counting and imaging different wells of treated plates, indicated that 7D9 antibody had a more significant (P<0.01) cytotoxic effect on cancer cell lines than the control cells.
Conclusion: HCG targeting monoclonal antibodies can be used for targeted cancer therapy, as human cancer cells express hCG gene. 7D9 antibody that exhibits protease activity is a proper candidate for this purpose, as it possesses both antagonistic and enzymatic properties.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Aldehyde dehydrogenase 1 (ALDH1) is a marker of normal and malignant human mammary stem cells that has been reported to be associated with poor prognosis. Studies on the detection of ALDH1+ cells can help the treatment of patients with breast cancer. The aim of this study was to determine the activity of ALDH1 in breast cancer and its relationship with the pathological features of the tumors.
Methods:  ALDH1 activity was studied by immunohistochemistry in 121 paraffin-embedded histological samples of breast cancer patients from Department of Pathology of Milad Hospital, Tehran, Iran during 2006-2007. The relationship of ALDH1 with the pathological features of the tumors (size, grade, lymph node metastasis and vascular invasion) was also investigated.
Results:  Eighty-five percent of breast cancer samples expressed ALDH1 in their cytoplasm with a wide range of intensity (weak, moderate and strong), while 18 samples (14.9%) were completely negative. The majority of cases (97.1%) showed ALDH1 positivity in the stroma of tumors which varied from weak (2.9%) to strong (73.5%). ALDH1 H-score (ALDH1% × intensity) of tumor cells varied from 0 to 240 (mean= 80). ALDH1 H-score was ≤80 in 62 (51.2%) and >80 in 59 (48.8%) samples. There was no statistically significant relationship between ALDH1 H-score and age (P=0.358), tumor size (P=0.375), tumor grade (P=0.207), lymph node metastasis (P=0.125) or vascular invasion (P=0.190).
Conclusion: ALDH1 activity was demonstrated in 85.1% of breast cancer samples although its level of expression was not correlated with the pathologic features of breast tumors.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: More than 80 years, the standard treatment of locally advanced cervical cancer was radiotherapy. However, based on several phase III randomized clinical trials in the past decade, concurrent cisplatin-based chemoradiotherapy is the current standard of treatment for this disease. Gemcitabine has potent radiosensitizing properties in preclinical and clinical trials, so it can be utilized simultaneously with radiation.
Methods:  Thirty Women with untreated invasive squamous-cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study in Radiation Oncology department of Imam Khomeini Hospital in Tehran from September 2009 to September 2010. Sixty mg/m² gemcitabine followed by 35 mg/m² cisplatin were concurrently administered with radiotherapy to the whole pelvic region on day one of each treatment week for five weeks One and three months after treatment, patients underwent a complete physical examination and MRI to determine the response to treatment.
Results:  The mean age of the participants was 58.13±11.83 (29-78) years. After 3 months of treatment, 73.3% had complete and 26.7% had partial response to treatment. Grade 3 anemia was seen in 10%, grade 3 thrombocytopenia in 3.3% and grade 3 leukopenia in 10% of the patients.
Conclusion: According to the positive results of this study in stage IIB, further phase II and III clinical trials are suggested to evaluate the role of chemoradiation by gemcitabine in advanced cervical cancers.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Breast cancer is the most common form of hereditary cancer worldwide and is an important cause of morbidity and mortality. Approximately 5-10% of breast and ovarian cancers are due to the highly penetrating germline mutations in cancer predisposing genes. Two genes, BRCA1 and BRCA2, account for at least half of these cases. The demand for BRCA1 and BRCA2 mutation screening is rapidly increasing as their identification will affect the medical management of people at increased risk for the disease. Therefore, the aim of this study was to investigate BRCA1/2 mutations in 100 high risk Iranian families.
Methods:  One hundred families who met the minimal risk factors for breast/ovarian cancer were screened among the families referred to Kawsar Human Genetics Research Center for the diseases in 2009-2011. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened for by direct sequencing and MLPA in both patients and the controls.
Results:  In the present study, we could detect the following novel mutations: p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Asn1403Asp, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Leu6Val, p.Arg7Cys, p.Leu15Ile, p.Ser177Thr, IVS7+83(-TT), IVS8 -70(-CATT), IVS2+9(G>C), IVS1-20(G>A), IVS1-8(A>G), p.Met1Ile, IVS2+24(A>G), IVS5-8 (A>G), IVS2(35-39)TTcctatGAT, IVS13+9 G>C in BRCA1 and p.Glu1391Gly, p. Val1852Ile, IVS6-70(T>G), 1994-1995 (InsA) in BRCA2.
Conclusion: Ten mutations seemed to be pathogenic and the disease-causing mutations were seen in 16% of the families. In addition, from the total number of substitutions and reassortments (42), 80% related to BRCA1 and 20% to mutations in BRCA2 genes.