• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7651-7656
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• 2013

Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.

• The Korean Journal of Pain
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• 제29권4호
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• pp.249-254
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• 2016

Background: This study aimed to investigate the effect of strenuous exercise on ${\beta}$-endorphine (${\beta}$-END) level in fibromyalgia (FM) patients compared to healthy subjects. Methods: We enrolled 30 FM patients and 15 healthy individuals. All study participants underwent a treadmill exercise test using modified Bruce protocol (M.Bruce). The goal of the test was achieving at least 70% of the predicted maximal heart rate (HRMax). The serum levels of ${\beta}$-END were measured before and after the exercise program. Measurements were done while heart rate was at least 70% of its predicted maximum. Results: The mean ${\pm}$ the standard deviation (SD) of exercise duration in the FM and control groups were $24.26{\pm}5.29$ and $29.06{\pm}3.26$ minutes, respectively, indicating a shorter time to achieve the goal heart rate in FM patients (P < 0.003). Most FM patients attained 70% HRMax at lower stages (stage 2 and 3) of M.Bruce compared to the control group (70% versus 6.6%, respectively; P < 0.0001). Compared to healthy subjects, FM patients had lower serum ${\beta}$-END levels both in baseline and post-exercise status ($Mean{\pm}SD$: $122.07{\pm}28.56{\mu}g/ml$ and $246.55{\pm}29.57{\mu}g/ml$ in the control group versus $90.12{\pm}20.91{\mu}g/ml$ and $179.80{\pm}28.57{\mu}g/ml$ in FM patients, respectively; P < 0.001). Conclusions: We found that FM patients had lower levels of ${\beta}$-END in both basal and post-exercise status. Exercise increased serum the ${\beta}$-END level in both groups but the average increase in ${\beta}$-END in FM patients was significantly lower than in the control group.

• The Korean Journal of Pain
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• 제30권3호
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• pp.176-182
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• 2017

Background: Current evidence suggests that intravenous magnesium sulfate might be effective for reducing migraine pain. In a recent pilot study, we showed that intravenous caffeine citrate could reduce the severity of migraine headache. The objective of this study is to investigate the efficacy of intravenous caffeine citrate vs. magnesium sulfate for management of acute migraine headache. Methods: We conducted a prospective quasi-experimental study from January until May 2016 in two educational medical centers of Shahid Beheshti University of Medical Sciences (Shoahadaye Tajrish Hospital and Imam Hossein Hospital), Tehran, Iran. The study included patients who were referred to the emergency department and met the migraine diagnosis criteria of the International Headache Society. Patients were allocated into 2 groups receiving either 60 mg intravenous caffeine or 2 g intravenous magnesium sulfate. The pain scores, based on the visual analog scale, were recorded on admission, as well as one and two hours after receiving the drug. A Chi-Square test and student t-test were used for analysis of baseline characteristics. A Mann-Whitney U test and Wilcoxon singed rank test were used to analyze differences in the visual analogue scale (VAS) score between and within the groups respectively. Results: In total, 70 patients (35 patients in each group) with the mean age of $33.1{\pm}11.3years$ were included (64.3% female). For the Caffeine citrate group, the median pain score decreased from 9.0 (2.0) to 5.0 (4.0) after one hour and to 3.0 (4.0) after two hours. For the magnesium sulfate group, the pain score decreased from 8.0 (2.0) to 2.0 (2.0) after one hour and to 0.0 (1.0) after two hours. Both intravenous caffeine citrate and intravenous magnesium sulfate reduced pain scores significantly but the magnesium sulfate group showed more improvement than the Caffeine citrate group after one hour (P < 0.001) and after two hours (P < 0.001). Conclusions: It is likely that both intravenous caffeine and intravenous magnesium sulfate can reduce the severity of migraine headache. Moreover, intravenous magnesium sulfate at a dose of 2 g might be superior to intravenous caffeine citrate 60 mg for the short term management of migraine headache in emergency departments.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8553-8557
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• 2016

Background: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. Conclusions: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.481-487
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• 2013

Following breast cancer diagnosis, women often attempt to modify their lifestyles to improve their health and prevent recurrence. These behavioral changes typically involve diet and physical activity modification. The aim of this study was to determine association between healthy eating habits and physical activity with quality of life among Iranian breast cancer survivors. A total of 100 Iranian women, aged between 32 to 61 years were recruited to participate in this cross-sectional study. Eating practices were evaluated by a validated questionnaire modified from the Women's Healthy Eating and Living (WHEL) study. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). A standardized questionnaire by the European Organization of Research and Treatment of Cancer Quality of Life and its breast cancer module (EORTC QLQ-C30/+BR-23) were applied to determine quality of life. Approximately 29% of the cancer survivors were categorized as having healthy eating practices, 34% had moderate eating practices and 37% had poor eating practices based on nutrition guidelines. The study found positive changes in the decreased intake of fast foods (90%), red meat (70%) and increased intake of fruits (85%) and vegetables (78%). Generally, breast cancer survivors with healthy eating practices had better global quality of life, social, emotional, cognitive and role functions. Results showed that only 12 women (12%) met the criteria for regular vigorous exercise, 22% had regular moderate-intensity exercise while the majority (65%) had low-intensity physical activity. Breast cancer survivors with higher level of physical activity had better emotional and cognitive functions. Healthy eating practices and physical activity can improve quality of life of cancer survivors. Health care professionals should promote good dietary habits and physical activity to improve survivor's health and quality of life.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.91-96
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• 2013

Background: p53 alterations have been implicated in the development of many cancers, such as gastric cancer, but there is no evidence of p53 intron alterations in gastritis lesions. The aim of this study was to investigate the p53 intron alterations in gastritis along with p53 and mismatch repair protein expression and microsatellite status. Materials and Methods: PCR-sequencing was conducted for introns 2-7 on DNA extracted from 97 paired samples of gastritis lesions and normal adjacent tissue. Abnormal accumulation of p53 and mismatch repair proteins was investigated using immunohistochemistry. In addition, microsatellite status was evaluated with reference to five mononucleotide markers. Results: Gastritis cases included 41 males and 56 females in the age range of 15-83 years, 87.6% being H.pylori positive. IVS2+38, IVS3ins16 and IVS7+72 were the most polymorphic sites. Their minor allele frequency values were as follows: 0.38, 0.21 and 0.06, respectively. Samples with GG genotype at IVS2+38 and CT at IVS7+72 had no insertion. Moreover, most of the stable samples (91.9 %) had a G allele at IVS2+38. All of the samples were IHC negative for p53 protein, microsatellite stable and expressed mismatch repair proteins. p53 alterations were prominent in the H. Pylori+ group, but without statistical significance. Conclusions: According to our results, some p53 polymorphisms such as IVS2+38, IVS3ins16 and IVS7+72, because of their correlations together or with microsatellite status may contribute to gastritis development. However, so far effects on p53 expression and function remain unclear. Therefore, a comprehensive survey is needed to delineate their biological significance.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3727-3731
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• 2016

Background: The most common type of ocular lymphoma is non-Hodgkin lymphoma (NHL), categorized into two groups: indolent (slow growing) and aggressive (rapid growing). Differentiating benign reactive lymphoid hyperplasia (RLH) from malignant ocular adnexal lymphoma (OAL) is challenging. Histopathology, immunohistochemistry (IHC) and flow cytometry have been used as diagnostic tools in such cases. Materials and Methods: In this retrospective case series, from 2002 to 2013 at Farabi Eye Center, 110 patients with ocular lymphoproliferative disease were enrolled. Prevalence, anatomical locations, mean age at diagnosis and the final diagnosis of the disease with IHC were assessed. Comparison between previous pathologic diagnoses and results of IHC was made. Immunoglobulin light chains and B-cell and T-cell markers and other immuno-phenotyping markers including CD20, CD3, CD5, CD23, CD10, CYCLIND1 and BCL2 were evaluated to determine the most accurate diagnosis. The lymphomas were categorized based on revised European-American lymphoma (REAL) classification. Results: Mean age ${\pm}$ SD (years) of the patients was $55.6{\pm}19.3$ and 61% were male. Patients with follicular lymphoma, large B-cell lymphoma or chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) tended to be older. Nine patients with previous diagnoses of low grade B-cell lymphoma were re-evaluated by IHC and the new diagnoses were as follows: extranodal marginal zone lymphoma(EMZL) (n=1), SLL(n=1), mantle cell lymphoma (MCL) (n=3), reactive lymphoid hyperplasia RLH (n=2). Two cases were excluded due to poor blocks. Flow cytometry reports in these seven patients revealed SLL with positive CD5 and CD23, MCLwith positive CD5 and CyclinD1 and negative CD23, EMZL with negative CD5,CD23 and CD10. One RLH patient was negative for Kappa/Lambda and positive for CD3 and CD20 and the other was positive for all of the light chains, CD3 and CD20. Orbit (49.1%), conjunctiva (16.1%) and lacrimal glands (16.1%) were the most common sites of involvement. Conclusions: Accurate pathological classification of lesions is crucial to determine proper therapeutic approaches. This can be achieved through precise histologic and IHC analyses by expert pathologists.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6101-6104
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• 2012

Background: Breast cancer accounts about one million from total annual ten million new diagnosed cases of neoplasia worldwide and is the main cause of death due to cancer in women. Tamoxifen is the most popular selective estrogen receptor modulator used in anti estrogen treatments. Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). This study surveyed copy number variation of the CYP2D6 gene and its possible correlation with Tamoxifen resistance in breast cancer patients. Methods: This case control study was performed on samples taken from 79 patients with breast cancer who used tamoxifen in Yazd and Tehran Cities, Iran. Real time reactions were conducted for 10 healthy samples using the comparative $C_t$ (Cycles threshold) method, each pair of genes being compared and samples with ratios around 1 were taken as control samples. Proliferation reactions were done by Real-Time PCR ABI Prism 7500. All registered data were transformed into SPSS 15 program and analyzed. Results: Efficiency of PCR for both CYP2D6 and ALB genes was 100%. From all 23 drug resistant patients 21.7% had one copy, 47.8% two copies and 30.4% had three copies. Also from all 56 drug sensitive patients, 26.8% had one copy, 51.8% two copies and 21.4% had three copies. The percentage of patients with one and two copies was similar between two groups but patients with three copies were more likely to belong to the drug resistant group more. Odd ratios for one and two copies were 0.759 and 0.853 respectively, indicating possible protective effects while that for three copies was 1.604. Conclusions: Based on our study there is no significant link between CYP2D6 gene copy numbers and tamoxifen resistance in women with breast cancer. But more studies considering other influencing factors appear warranted.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6505-6510
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• 2012

Background: CYP2E1 encodes an enzyme which is mainly involved in bioactivation of potential carcinogens such as N-nitrosamines. Polymorphisms in the gene have been reported to be associated with cancer. The aim of this study was to evaluate genotype distributions and allele frequencies of five CYP2E1 polymorphisms in Iran Materials and Methods: Two hundred healthy individuals of an Iranian population from the southwest were included in this study. PCR-restriction fragment length polymorphism and Tetra-ARMS PCR methods were applied for CYP2E1 genotyping. Results: The allele frequencies for $^*5B$, $^*6$, $^*7B$, $^*2$, and $^*3$ were calculated to be 1.5%, 16%, 28.5%, 0%, and 2.75% respectively. Results of this study showed that no significant differences in genotype and allele frequencies of five single nucleotide polymorphisms with respect to the gender and tribes. The chi-square test showed that the genotype frequencies of $CYP2E1^*5B$ were similar to Caucasians, but the distribution of $CYP2E1^*6$ genotypes was similar to Asians. The frequencies of $CYP2E1^*2$ (0%) and $CYP2E1^*3$ (2.75%) alleles were within the range for Caucasians and Orientals. In the case of $CYP2E1^*7B$, the data werelimited. Accordingly, the results were only compared with Europeans and the comparison showed significant differences. Conclusions: In conclusion, ethnic and geographic differences may explain discrepancies in the prevalence of CYP2E1 polymorphisms.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7049-7054
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• 2014

Background: Almost half of the breast cancer patients with positive sentinel lymph nodes have no additional disease in the remaining axillary lymph nodes. This group of patients do not benefit from complete axillary lymph node dissection. This study was designed to assess the clinicopathologic factors that predict non-sentinel lymph node metastasis in Iranian breast cancer patients with positive sentinel lymph nodes. Materials and Methods: The records of patients who underwent sentinel lymph node biopsy, between 2003 and 2012, were reviewed. Patients with at least one positive sentinel lymph node who underwent completion axillary lymph node dissection were enrolled in the present study. Demographic and clinicopathologic characteristics including age, primary tumor size, histological and nuclear grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and number of harvested lymph nodes, were evaluated. Results: The data of 167 patients were analyzed. A total of 92 (55.1%) had non-sentinel lymph node metastasis. Univariate analysis of data revealed that age, primary tumor size, histological grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio, were associated with non-sentinel lymph node metastasis. After logistic regression analysis, age (OR=0.13; 95% CI, 0.02-0.8), primary tumor size (OR=7.7; 95% CI, 1.4-42.2), lymphovascular invasion (OR=19.4; 95% CI, 1.4-268.6), extracapsular invasion (OR=13.3; 95% CI, 2.3-76), and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio (OR=20.2; 95% CI, 3.4-121.9), were significantly associated with non-sentinel lymph node metastasis. Conclusions: According to this study, age, primary tumor size, lymphovascular invasion, extracapsular invasion, and the ratio of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes, were found to be independent predictors of non-sentinel lymph node metastasis.