The Effect of Melatonin on Increasing the Health Related Quality of Life in Non-Metastatic Breast Cancer Patients: Three-Year Follow up a Clinical Trial.

INTRODUCTION: Although breast cancer is common worldwide, if diagnosed early and treated on time, the probability of recovery is high and patients often experience a long life. Reducing the quality of life is a common side effect in patients. Melatonin may have an important role in fatigue, sleep disorders and, as a result, the health-related quality of life (HRQoL) in people. About 184 patients with breast cancer were enrolled in 2 groups: intervention with daily melatonin intake of 18 mg for 3 years (93 patients) and the control group with placebo intake (91 patients). Health-related quality of life and the effect of melatonin on increasing that were evaluated with the EORTC QLQ-C30 questionnaire, third edition at the beginning, 2 months later and 3 years after the beginning of the study. RESULTS: The general score of the HRQoL was significantly different both in the passage of time and in the comparative study of the 2 groups, and it was better in the melatonin group (P < .05). CONCLUSION: Long-term use of 18 mg of melatonin for 3 years in patients with non-metastatic breast cancer can lead to an increase in the patients' quality of life.

A human pilot study on positive electrostatic charge effects in solid tumors of the late-stage metastatic patients.

Background: Correlative interactions between electrical charges and cancer cells involve important unknown factors in cancer diagnosis and treatment. We previously reported the intrinsic suppressive effects of pure positive electrostatic charges (PEC) on the proliferation and metabolism of invasive cancer cells without any effect on normal cells in cell lines and animal models. The proposed mechanism was the suppression of pro-caspases 3 and 9 with an increase in Bax/Bcl2 ratio in exposed malignant cells and perturbation induced in the KRAS pathway of malignant cells by electrostatic charges due to the phosphate molecule electrostatic charge as the trigger of the pathway. This study aimed to examine PECs as a complementary treatment for patients with different types of solid metastatic tumors, who showed resistance to chemotherapy and radiotherapy. Methods: In this study, solid metastatic tumors of the end-stage patients (n = 41) with various types of cancers were locally exposed to PEC for at least one course of 12 days. The patient's signs and symptoms, the changes in their tumor size, and serum markers were followed up from 30 days before positive electrostatic charge treating (PECT) until 6 months after the study. Results: Entirely, 36 patients completed the related follow-ups. Significant reduction in tumor sizes and cancer-associated enzymes as well as improvement in cancer-related signs and symptoms and patients' lifestyles, without any side effects on other tissues or metabolisms of the body, were observed in more than 80% of the candidates. Conclusion: PECT induced significant cancer remission in combination with other therapies. Therefore, this non-ionizing radiation would be a beneficial complementary therapy, with no observable side effects of ionizing radiotherapy, such as post-radiation inflammation.

Positive electrostatic therapy of metastatic tumors: selective induction of apoptosis in cancer cells by pure charges.

BACKGROUND: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. METHODS: We interacted normal and cancer cell lines and animal tumors with PECs by connecting a charged patch to cancer cells and animal tumors. many biochemical, molecular and radiological assays were carried out on PEC treated and control samples. RESULTS: Correlative interactions between electrostatic charges and cancer cells contain critical unknown factors that influence cancer diagnosis and treatment. Different types of cell analyses prove PEC-based apoptosis induction in malignant cell lines. Flowcytometry and viability assay depict selective destructive effects of PEC on malignant breast cancer cells. Additionally, strong patterns of pyknotic apoptosis, as well as downregulation of proliferative-associated proteins (Ki67, CD31, and HIF-1α), were observed in histopathological and immunohistochemical patterns of treated mouse malignant tumors, respectively. Quantitative real-time polymerase chain reaction results demonstrate up/down-regulated apoptotic/proliferative transcriptomes (P21, P27, P53/CD34, integrin α5, vascular endothelial growth factor, and vascular endothelial growth factor receptor) in treated animal tumors. Expression of propidium iodide in confocal microscopy images of treated malignant tissues was another indication of the destructive effects of PECs on such cells. Significant tumor size reduction and prognosis improvement were seen in over 95% of treated mouse models with no adverse effects on normal tissues. CONCLUSION: We discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. The findings were statistically and observationally significant when compared to radio/chemotherapy-treated mouse models. As a result, this nonionizing radiation may be used as a practical complementary approach with no discernible side effects after passing future human model studies.

The design and fabrication of nanoengineered platinum needles with laser welded carbon nanotubes (CNTs) for the electrochemical biosensing of cancer lymph nodes.

A new biosensor for detecting cancer involved sentinel lymph nodes has been developed via the electrochemical tracing of fatty acid oxidation as a distinct metabolism of malignant cells invading lymph nodes (LNs). The system included integrated platinum needle electrodes that were decorated by carbon nanotubes (as hydrophobic agents) through laser-assisted nanowelding. It was applied to record the dielectric spectroscopy data from LN contents via electrochemical impedance spectroscopy. The system was applied for dielectric spectroscopy of LN contents via electrochemical impedance approach. The reduced lipid content of involved LNs, due to fat metabolism by invasive cancer cells, would decrease the charge transfer resistance (RCT) of the LNs with respect to their normal counterparts. Multi-walled carbon nanotubes (MWCNTs) with superhydrophobic properties were used to enhance the interaction of Pt needle electrodes with the lipidic contents of lymph nodes. This is the first time that a fatty acid metabolism-based sensing approach has been introduced to detect involved LNs. Moreover, a novel electrode decorating method was applied to enhance the interfacial contact of this lipid detection probe (LDP). In order to avoid doubt about the biocompatibility of ferrocyanide, [Fe(CN)6]4- and ferricyanide, [Fe(CN)6]3-, a biocompatible injectable metal ion-based material, ferric carboxymaltose, was selected and applied as the electrolyte for the first time. Rabbit LNs were tested using the LDP in the animal model phase. The system was then used in vitro on 122 dissected human LNs in the operating room. Calibration of the results showed an excellent match between the dielectric response of the LDP (known as charge transfer resistance (RCT)) and the final pathological diagnoses. The LDP may have a promising future after further clinical investigations for intra-operative distinction between normal and cancerous LNs.

Breast Cancer and Ovulation Induction Treatments.

BACKGROUND: This study was performed to determine whether the use of ovulation induction drugs in treatment of infertility have a significant effect on the risk of breast cancer. PATIENTS AND METHODS: This case control study (928 cases, 928 controls), was performed in the gynecology and oncology clinics of Shahid Beheshti University of Medical Sciences between 2011 and 2013. Data were collected via in-person interviews using a questionnaire, which included demographic and gynecologic information. Statistical analysis was performed using SPSS statistics software version 20 (IBM Corp). RESULTS: The use of ovulation induction drugs was not significantly associated with an increased risk of breast cancer (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.7-1.855) among women with infertility (OR, 1.28; 95% CI, 0.8-1.95). CONCLUSION: We observed no statistically significant relationship between infertility and ovulation induction drugs with the risk of breast cancer, except for significant increases in the risk of breast cancer among patients who had used fertility drugs for >6 months.

Mutation Spectra of BRCA Genes in Iranian Women with Early Onset Breast Cancer - 15 Years Experience.

Breast cancer is the most common cancer in Iran. In the recent years an upward trend has been observed in the Iranian population. Early detection by molecular approaches may reduce breast cancer morbidity and mortality. We provided consultation to 3,782 women diagnosed with early onset breast cancer during the past 15 years (1999-2014). To establish a data set for BRCA gene alterations of the Iranian families at risk, two hundred and fifty four women who met our criteria were analyzed. A total number of 46 alterations including 18 variants with unknown clinical significance (39.1%), 18 missense mutations (39.1%), 7 Indels (15.2%) and 3 large rearrangement sequences (6%) were identified. Further scanning of affected families revealed that 49% of healthy relatives harbor identical causative mutations. This is the first report of comprehensive BRCA analysis in Iranian women with early onset breast cancer. Our findings provide valuable molecular data to support physicians as well as patients for the best decision making on disease management.

Lactating breast abscess: a rare presentation of adenosquamous breast carcinoma.

We report the case of a 33-year-old lactating woman who presented with a 10-cm breast abscess. Biopsy of the abscess wall revealed a poorly differentiated invasive ductal carcinoma. The patient had no family history of breast cancer or other risk factors for breast cancer. The disease was considered to be a large noninflammatory invasive breast cancer, for which the patient received neoadjuvant chemotherapy, breast-conserving surgery using axillary dissection (the patient did not consent to a mastectomy), and postoperative radiotherapy. Final histologic examination revealed a 4-cm, triple negative, high-grade adenosquamous carcinoma. At follow-up four years after surgery, the patient was doing well with no signs of recurrence. Adenosquamous carcinoma is an extremely rare disease that mainly presents in low-grade forms. High-grade forms are aggressive and frequently present with axillary involvement. To the best of our knowledge, there has been no report of adenosquamous carcinoma presenting as a breast abscess in the literature. The case we report highlights that, although rare, cancer should be considered in lactating breast abscesses.

Abnormal expression of e-cadherin in gastric adenocarcinoma, and its correlation with tumor histopathology and helicobacter pylori infection.

BACKGROUND: Gastric cancer is one of the leading cancers in the world especially in Iran. There are many genomic and molecular factors that cause gastric cancer to occur, and also there are many markers that associate with tumor invasiveness. E-cadherin is a tumor suppressor gene which produces E-cadherin transmembrane protein, a molecule which plays an important role in adhesion and differentiation of epithelial cells. OBJECTIVES: In this study, we evaluated the prevalence of abnormal E-cadherin expression in Iranian patients with gastric adenocarcinoma, and tried to find its correlation with H. pylori infection and tumor histopathology. MATERIALS AND METHODS: A historical cohort survey was performed on tissue samples obtained from 95 total or partial gastrectomy with gastric adenocarcinoma. The immunohistochemistry and Giemsa staining were used to assess E-cadherin expression, and H- pylori infection respectively. The association between abnormal E-cadherin expression and tumor histopathology characteristics include depth of tumor invasion, tumor differentiation, tumor phenotype, tumor type, tumor size, neurovascular invasion of tumor, and regional lymph node involvement and H- pylori infection and patient's age and sex, were evaluated in all patients. RESULTS: Abnormal E-cadherin expression was noted in 38% of patients, and 59% of patients were infected with H-pylori. A significant correlation was seen between abnormal E-cadherin expression, and tumor grade and regional lymph node involvement. We could not find any significant association between abnormal E-cadherin expression and H- pylori infection, patient's age and sex, tumor phenotype, tumor type, depth of tumor invasion, tumor size, and neurovascular invasion of tumor. CONCLUSIONS: Abnormal E-cadherin expression is a common phenomenon in gastric adenocarcinoma. The study showed a significant correlation between abnormal E-cadherin expression and tumor grade and regional lymph node involvement; so, abnormal E-cadherin expression may be used as a predictive factor for tumor invasiveness in gastric adenocarcinoma.

The validity of MRI in evaluation of tumor response to neoadjuvant chemotherapy in locally advanced breast cancer.

BACKGROUND: Physical Examination (PE) and breast MRI are two of the currentmethods which have usually used in diagnosis of primary breast cancer. Their accuracy in detection of: either complete response or presence of residual tumor, however, has not yet been established in patients who have been received Neoadjuvant Chemotherapy (NAC).The purpose of this study was to evaluate the diagnostic accuracy of breast MRI in assessment of residual neoplastic tissue after NAC in patients with Locally Advanced Breast Cancer (LABC). METHODS: Twenty patients with LABC have undergone contrast-enhanced MRI before and after the NAC. Considering histology as the gold standard, the tumor sizes in MRI and PE have compared with the histology results. We have calculated for all below: the accuracy, sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for each of MRI and physical examination, as well as Pearson's correlation coefficients between the results of MRI and PE, and their histology results. RESULTS: We have found an accuracy of 85% for MRI with a sensitivity of 100%, a specificity of 50%, a PPV of 83.3%, and an NPV of 100%. In addition, theaccuracy for PE was 70% with a sensitivity of 71.4%, a specificity of 66.6%, a PPV of 83.3%, and an NPV of 50%. In this study, the calculated Pearson's correlation coefficient for MRI and histology was 0.817 (p<0.0001) versus 0.26 (p=0.26) for correlation between PE and histology. CONCLUSION: MRI has higher sensitivity but less specificity than PE for detection of residual tumor after NAC in locally advanced breast carcinoma. Also, the tumor size that has measured by MRI had highly correlation with the histology.

IMPST: A New Interactive Self-Training Approach to Segmentation Suspicious Lesions in Breast MRI.

Breast lesion segmentation in magnetic resonance (MR) images is one of the most important parts of clinical diagnostic tools. Pixel classification methods have been frequently used in image segmentation with two supervised and unsupervised approaches up to now. Supervised segmentation methods lead to high accuracy, but they need a large amount of labeled data, which is hard, expensive, and slow to be obtained. On the other hand, unsupervised segmentation methods need no prior knowledge and lead to low performance. However, semi-supervised learning which uses not only a few labeled data, but also a large amount of unlabeled data promises higher accuracy with less effort. In this paper, we propose a new interactive semi-supervised approach to segmentation of suspicious lesions in breast MRI. Using a suitable classifier in this approach has an important role in its performance; in this paper, we present a semi-supervised algorithm improved self-training (IMPST) which is an improved version of self-training method and increase segmentation accuracy. Experimental results show that performance of segmentation in this approach is higher than supervised and unsupervised methods such as K nearest neighbors, Bayesian, Support Vector Machine, and Fuzzy c-Means.

Crude and age-specific incidence rate patterns for histopathologic subtypes of ovarian cancer in Iran.

BACKGROUND: The purpose of this study was to report age-specific incidence rates of histopathological subtypes of ovarian cancer in Iran. METHODS: Data published by the pathology-based Cancer Registry, Iranian Ministry of Health and Medical Education for the year 2004, was utilized. This study included 793 new ovarian cancer cases which were analyzed by SPSS software (version 13). RESULTS: There were 45 different histologies reported in 793 new cases which were categorized into ten major groups. Epithelial tumors displayed the highest age specific incidence rate, followed by germ cell tumors. Serous epithelial tumors were the most common in the epithelial group. CONCLUSION: The age-specific incidence rate of ovarian cancer varies based on histology.

Survival of ovarian cancer in Iran: 2000-2004.

OBJECTIVE: The aim of this study was to estimate the 5-year survival of ovarian cancer in Iran between 2000 and 2004, according to age and histology. METHODS: Cancer registry of Iran, 2000-2004, was used covering nearly 80% of all ovarian cancers and 100% of all pathologically diagnosed ovarian cancers. RESULTS: Of 1,246 new ovarian cancer cases, 451 were available for further follow-up, which revealed 169 deaths and 282 live cases. The 5-year survival was 61%; 85% for germ cell tumors and 59% for epithelial tumors. Survival of serous, mucinous, endometrioid and clear cell histologic subtypes of epithelial tumors was 41%, 62%, 76% and 78%, respectively. Young patients with epithelial tumors (below 45) displayed significantly better 5-year survival rates (63% versus 53%). CONCLUSION: we found that ovarian cancer had a better survival rate in Iran in comparison to other regions. We also reviewed all probable confounding factors or real causes. In this study, age and histology affected survival.