Dietary insulin indices and low-carbohydrate diet and the odds of colorectal cancer: a case-control study.

BACKGROUND: Regarding the role of insulin and insulin-inducing dietary factors in some cancers' etiology, we hypothesized that the risk of colorectal cancer may be lessened by following a lower carbohydrate and insulinogenic diet. Therefore, we performed this study to explore the association between a low-carbohydrate diet and insulin indices and the odds of colorectal cancer. METHOD: This hospital-based case-control study was conducted on 150 newly diagnosed colorectal cancer patients and 300 healthy age- and sex-matched hospitalized controls. A valid and reliable food frequency questionnaire was used to calculate the insulin indices and low-carbohydrate diet score. Multivariate logistic regression was used to estimate the association between insulin indices and low-carbohydrate diet and the odds of colorectal cancer. RESULT: After adjusting for potential confounders, individuals in the highest tertile of insulin indices had a higher risk of colorectal cancer (OR insulin index  = 3.46; 95% CI, 2.00-5.96; OR insulin load  = 2; 95% CI, 1.17-3.41). No association was found between a low-carbohydrate diet and colorectal cancer (OR = 1.55; 95% CI, 0.85-2.84). CONCLUSION: Current results demonstrated that a high insulinemic diet was associated with a higher risk of colorectal cancer.

Evaluation of the Effect of Carvedilol in Preventing Right Ventricular Dysfunction in Breast Cancer Patients Receiving Anthracycline.

Background: Today, it has been shown that it is possible for right ventricular (RV) wall motion abnormalities or RV functional disorders to occur during cancer treatment. Now, considering the effect of carvedilol on beta 1, 2, and alpha receptors and its antioxidant properties, it seems that it can prevent RV abnormalities. Therefore, the aim of this study was to investigate the possible protective effects of carvedilol in preventing RV dysfunction in patients with breast cancer treated with anthracyclines. Materials and Methods: The present single-blind clinical trial study was performed on 23 patients with breast cancer that 12 of them received only the anthracycline antineoplastic doxorubicin (Adriamycin®) chemotherapy (control group) and 11 patients received carvedilol in addition to anthracycline. To evaluate the effect of carvedilol, patients underwent transthoracic echocardiography before intervention and 2 weeks after the end of treatment with anthracyclines. Results: The two parameters of RV ejection fraction and RV fractional area change in the carvedilol group with a mean of 66.41% ± 8.10% and 51.85% ± 6.89% were slightly higher than the control group with a mean of 64.58% ± 6.83% and 50.48 ± 5.79%, respectively, which was not statistically significant (P > 0.05). In contrast, RV S wave tissue Doppler imaging (S-TDI) in the control group with a mean of 0.13 ± 0.02 m/s was significantly lower than the carvedilol group with a mean of 0.14 ± 0.02 m/s (P = 0.022). Conclusion: According to the results of the present study, the effect of using carvedilol as a preservative on improving RV function was seen compared to the control group, although this difference was not statistically significant.

Treatment of insulin-dependent diabetes by hematopoietic stem cell transplantation.

Type 1 diabetes (T1D) is an autoimmune disease resulting from the demolition of ß-cells that are responsible for producing insulin in the pancreas. Treatment with insulin (lifelong applying) and islet transplantation (in rare cases and severe diseases), are standards of care for T1D. Pancreas or islet transplantation have some limitations, such as lack of sufficient donors and longtime immune suppression for preventing allograft rejection. Recent studies demonstrate that autologous hematopoietic stem cells (HSC) can regenerate immune tolerance against auto-antigens. Taking advantage of this feature, autologous HSC transplantation (auto-HSCT) is likely the only treatment for T1D that is associated with lasting and complete remission. None of the other evaluated immunotherapies worldwide had the clinical efficacy of auto-HSCT. Therapy with auto-HSCT is insulin-independent rather than reducing insulin needs or delaying loss of insulin production. This review provided the latest findings in auto-HSCT for treatment of T1D.

Immunohistochemical Expression Pattern of MLH1, MSH2, MSH6, and PMS2 in Tumor Specimen of Iranian Gastric Carcinoma Patients.

BACKGROUND: Gastric cancer is the third leading cause of cancer-related death. Determining molecular and histopathologic tumor features, which may contribute to the development or progression of gastric cancer, can improve the prognosis. Expression patterns of DNA repair proteins such as MLH1, MSH2, MSH6, and PMS2 that are associated with microsatellite instability (MSI) are some of the markers that are useful in predicting the prognosis of gastric cancer. PURPOSE: The purpose was to determine the immunohistochemical expression pattern of MLH1, MSH2, MSH6, and PMS2 in tumor specimens of Iranian gastric carcinoma patients. METHODS: In this prospective cohort, 186 consecutive patients with gastric cancer, attending Taleghani Hospital, were enrolled. The immunohistochemical expression patterns of MLH1, MSH2, MSH6, and PMS2 in tumor specimens among them were determined. RESULTS: The results of this study demonstrated that 91.4% of our gastric cancer patients were negative for MSI, and 8.6% of them were MSI positive. The positive MSI was seen in 5.9% and 15.7% of male and female subjects, respectively, with a significant difference (P = 0.043). The other variables were not related to MSI results (P > 0.05). CONCLUSION: According to the obtained results, the expression of MLH1, MSH2, MSH6, and PMS2 in tumor specimens is positive in 8.6% of the total Iranian gastric cancer sample size, which is mainly positive in female subjects. However, it is not related to the location and stage of the tumor.

Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial.

PURPOSE: The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC). METHODS: This Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m2 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements. FINDINGS: A total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210 days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol population (90% CI, 0.46-1.35; P = 0.47). The upper limit for the 2-sided 90% CI was lower than the margin of 1.44, indicating that the biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55-1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm. IMPLICATIONS: The proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and tolerability was comparable between the 2 drugs. ClinicalTrials.gov identifier: NCT03288987.

A mutational and expressional analysis of DNMT3A in acute myeloid leukemia cytogenetic subgroups.

OBJECTIVES: Despite numerous studies in order to determine the allele frequency and clinical impact of DNA methyltransferase 3 A (DNMT3A) gene mutations in acute myeloid leukemia (AML), reports about the expression analysis of this gene are rare and between the available, differences are evident. METHODS: In this study, we decided to investigate DNMT3A possible expression changes with regard to their mutation and cytogenetic status in a series of 96 AML patients. RESULTS: Mutations were founded in 17 of the 96 patients (17.7%) and associated with higher age and white blood cell count (P < 0.001). Our mutants have had shorter overall survival (OS) (P < 0.001) and relapse-free survival (RFS) (P = 0.011) than those without. Multivariate analysis showed that DNMT3A mutation is an independent prognostic indicator for OS and RFS (P < 0.001). In relation to expression results, we had over and under expression for our favorable and unfavorable cytogenetic subgroups, respectively (P = 0.005 and P < 0.001, respectively). In intermediate subgroup, total DNMT3A expression did not alter (P = 0.575). Interestingly, we noticed similar expression results for DNMT3A transcript 2, to that of the total. DISCUSSION AND CONCLUSION: In relation to DNMT3A expression, from the perspective of diagnostic application and its biological significance, it is difficult to accept its primacy over cytogenetic value in favorable and unfavorable subgroups and if so, we did not address this issue in our study due to sample size limitation. In intermediate subgroup, particularly in normal karyotype-AML, given the lack of convincing results, it seems unlikely that DNMT3A expression analysis could attract attention in diagnostic workup and risk prediction of AML.

Prognostic and predictive value of copy number alterations in invasive breast cancer as determined by multiplex ligation-dependent probe amplification.

BACKGROUND: Breast cancer is a leading cause of morbidity and mortality in women worldwide. About 70 % of breast cancers are estrogen receptor (ER) positive. Blocking estrogen action by tamoxifen has been the treatment of choice in ER positive breast cancers for more than 30 years. In the past, several studies have revealed associations between gene copy number alterations and responsiveness to tamoxifen therapy, but so far no single gene copy number alteration could completely explain the response variation observed between individual breast cancer patients. Here, we set out to perform a simultaneous analysis of copy number alterations of several genes involved in the prognosis and response to therapy by multiplex ligation-dependent probe amplification (MLPA). METHODS: A case-control study was designed encompassing 170 non-metastatic ER positive breast cancer patients (case group = 85, control group = 85). All patients in the control group had received standard adjuvant tamoxifen treatment for 5 years without any evidence of recurrence. Patients in the case group had experienced early recurrences while receiving tamoxifen treatment. 76 % of the patients of the case group and 73 % of the patients of the control group had received anthracycline-based adjuvant chemotherapy. Gene copy number alterations detected by MLPA in both groups were compared. RESULTS: Amplification of CCND1 (OR = 3.13; 95 % CI = 1.35 to 7.26; p = 0.006) and TOP2A (OR = 3.05; 95 % CI = 1.13 to 8.24; p = 0.022) were significantly more prevalent in the case group, compared to the control group. In a multivariate analysis CCND1 (p = 0.01) and TOP2A (p = 0.041) amplifications remained significant predictors of recurrence. CONCLUSIONS: Our results indicate that CCND1 amplification may serve as a useful biomarker for hormone responsiveness, and that TOP2A amplification may serve as a useful prognostic biomarker.

Efficacy of taxotere, thalidomide, and prednisolone in patients with hormone-resistant metastatic prostate cancer.

PURPOSE: To evaluate the efficacy and safety of combination treatment with thalidomide and taxotere in patients with hormone-resistant prostate cancer. MATERIALS AND METHODS: This clinical trial was performed on 16 patients with hormone-resistant prostate cancer. RESULTS: Mean age of the participants was 72.7 ± 5.39 years (range, 65 to 85 years). In 94% of patients who received the drug combination, prostate-specific antigen level decreased more than 50%. The mean time to progression was 15 months and mean survival time was 23 months. This combination therapy had some adverse events. CONCLUSION: Addition of anti-angiogenic agents, such as thalidomide, can improve therapeutic outcome in this group of patients.

Consolidation chemotherapy with docetaxel after platinum-based chemotherapy in patients with non-small cell lung cancer: a preliminary report.

BACKGROUND: The efficacy of second line chemotherapy for relapsed non small cell lung cancer has been established. In this study, we evaluated the efficacy and toxicity of maintenance therapy with docetaxel in patients with non-small cell lung cancer who were stabilized with first line chemotherapy and had good performance status before relapse. The primary objective was to determine one-year survival and the other objectives were evaluation of adverse effects and time to progression. MATERIALS AND METHODS: Eighteen patients with lung cancer were included in this study. All patients were at stage III and IV, without distant metastasis or neuropathy. All patients had been treated with platinum based regimen initially and were responsive or stable with no progression. The patients were treated with docetaxel 75 mg/m(2) for a total of 4 cycles repeated every 3 weeks. RESULTS: All patients accomplished 4 chemotherapy cycles and a total of 72 cycles were administered. The mean time of progression free survival (PFS) was 9-10 months and one- year survival (OS) was 94.4% without any significant adverse effect necessitating medical intervention. The mean survival time of patients was 18 (12-20) months. CONCLUSION: Using docetaxel as consolidation chemotherapy in patients with non small cell lung cancer can prolong time to progression of disease and probably patients' survival without significant adverse effects or negative impact on the quality of life.