The effects of chitosan-loaded JQ1 nanoparticles on OVCAR-3 cell cycle and apoptosis-related gene expression.

Background and purpose: Ovarian cancer is the deadliest gynecological cancer. Bromodomain and extra terminal domain (BET) proteins play major roles in the regulation of gene expression at the epigenetic level. Jun Qi (JQ1) is a potent inhibitor of BET proteins. Regarding the short half-life and poor pharmacokinetic profile, JQ1 was loaded into newly developed nano-carriers. Chitosan nanoparticles are one of the best and potential polymers in cancer treatment. The present study aimed to build chitosan-JQl nanoparticles (Ch-J-NPs), treat OVCAR-3 cells with Ch-J-NPs, and evaluate the effects of these nanoparticles on cell cycle and apoptosis-associated genes. Experimental approach: Ch-J-NPs were synthesized and characterized. The size and morphology of Ch-J-NPs were defined by DLS and FE-SEM techniques. OVCAR-3 cells were cultured and treated with Ch-J-NPs. Then, IC50 was measured using MTT assay. The groups were defined and cells were treated with IC50 concentration of Ch-J-NPs, for 48 h. Finally, cells in different groups were assessed for the expression of genes of interest using quantitative RT-PCR. Findings/Results: IC50 values for Ch-J-NPs were 5.625 µg/mL. RT-PCR results demonstrated that the expression of genes associated with cell cycle activity (c-MYC, hTERT, CDK1, CDK4, and CDK6) was significantly decreased following treatment of cancer cells with Ch-J-NPs. Conversely, the expression of caspase-3, and caspase-9 significantly increased. BAX (pro-apoptotic) to BCL2 (anti-apoptotic) expression ratio, also increased significantly after treatment of cells with Ch-J-NPs. Conclusion and implications: Ch-J-NPs showed significant anti-cell cyclic and apoptotic effects on OVCAR-3 cells.

Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: the non-interventional study coveNIS.

Cobimetinib/vemurafenib combination therapy is approved for treatment of adults with unresectable or metastatic BRAF V600 mutated malignant melanoma (mM). The non-interventional post-authorisation safety study coveNIS collected real-world data on cobimetinib/vemurafenib treatment focussing on overall survival (OS), safety and utilization. MM patients with brain metastases are usually excluded from clinical studies. coveNIS observed 2 cohorts: mM patients without (Cohort A) and with cerebral metastases (Cohort B), aiming to close the data gap for the latter population. A direct comparison of the 2 cohorts was not intended. The primary effectiveness objective was OS; the safety objective was the incidence of all and of serious adverse events (AEs). Secondary objectives included progression-free survival (PFS), time to development of cerebral metastasis (Cohort A) and time to central nervous system relapse (Cohort B). All statistical analyses were descriptive. Between 2017 and 2021, 95 patients were included (Cohort A: 54, Cohort B: 41 patients) at 32 sites in Germany. Median OS was 21.6 months in Cohort A, 7.4 months in Cohort B. Median PFS was 6.9 months in Cohort A, 5.2 months in Cohort B. The proportion of patients experiencing any AEs was 83.3% (Cohort A) and 87.8% (Cohort B). The two most common AEs in Cohort A were 'diarrhoea' (37%), 'vomiting' (20.4%) and 'pyrexia' (20.4%); in Cohort B 'diarrhoea' (36.6%) and 'fatigue' (22%). In conclusion, the OS rates in Cohort A and Cohort B of coveNIS are in line with the OS data from other trials with BRAF/MEK inhibitors for mM. No new safety signals were observed.

The Histopathological Findings in Appendectomy Specimens in an Iranian Population.

BACKGROUND: Appendicitis is one of the most common causes of acute abdominal surgeries. The importance of parasitic etiologies in the pathogenesis of appendicitis is not well known in appendectomy specimens on a large scale in southwestern Iran. The current study aimed to retrospectively assess the demographic data and histopathological records of appendicitis in a 28-year period in Fars province, southwestern Iran. MATERIALS AND METHODS: Histopathological records of 13,013 patients who had undergone surgeries for appendicitis at Dr. Ali Shariati Hospital, affiliated with the Fasa University of Medical Sciences from December 1993 to January 2021 were reviewed and data concerning the patients' demographic data and histopathological records were retrieved from each record. More than 6800 archived microscopic glass slides were also reviewed. RESULTS: From a total of 13,013 histopathological records of surgical excisions of appendicitis that were reviewed over a 28-year period, 8,189 (62.9%) were male and 4,842 (37.1%) were female. Patients' age ranged from 2 to 98 years, with a mean age of 24.68±19.87 years. The most common inflammatory changes were 5,687 (43.7%), 1,228 (9.4%), 670 (5.1%), 522 (4%), and 363 (2.8%) cases of acute appendicitis, suppurative appendicitis, early acute appendicitis, gangrenous appendicitis, and perforated appendicitis respectively. Microscopically, no viral inclusions, fungal elements, and histopathologic findings of bacterial causes were found. Parasitic infections such as helminthiasis were detected in 74 (0.6%) cases aged from 6 to 63. Enterobiasis (Syn. oxyuriasis, pinworm infection) accounted for 73 (98.6%) of the 74 helminthiases, while ascariasis accounted for 1 (1.4%). Out of 74 cases, 29 (39.2%) showed evidence of appendicitis. CONCLUSION: The results suggest that although parasitic agents are minor causes of appendicitis, these agents should be kept in mind during differential diagnosis. However, whether every parasitic infection leads to appendicitis is controversial.

ICAOD: An R Package for Finding Optimal designs for Nonlinear Statistical Models by Imperialist Competitive Algorithm.

Optimal design ideas are increasingly used in different disciplines to rein in experimental costs. Given a nonlinear statistical model and a design criterion, optimal designs determine the number of experimental points to observe the responses, the design points and the number of replications at each design point. Currently, there are very few free and effective computing tools for finding different types of optimal designs for a general nonlinear model, especially when the criterion is not differentiable. We introduce an R package ICAOD to find various types of optimal designs and they include locally, minimax and Bayesian optimal designs for different nonlinear statistical models. Our main computational tool is a novel metaheuristic algorithm called imperialist competitive algorithm (ICA) and inspired by socio-political behavior of humans and colonialism. We demonstrate its capability and effectiveness using several applications. The package also includes several theory-based tools to assess optimality of a generated design when the criterion is a convex function of the design.