A pilot study evaluating the feasibility of non-descent vaginal hysterectomy for benign gynecological indications in women in rural India

Background: Hysterectomy for benign indications is one of the common surgical procedures performed on women worldwide. Despite the available evidence favouring vaginal surgery still abdominal route is preferred in majority of women in rural India. Hence, this pilot study was done to determine the feasibility of Non-descent vaginal hysterectomy (NDVH) in rural India.Methods: All women planned for hysterectomy for benign indications (with no or minimal pelvic organ prolapse) during a period of six months were enrolled after taking informed consent and subsequently, underwent NDVH. Data was analyzed retrospectively with respect to duration of surgery, average blood loss, complications of surgery and duration of stay in the hospital.Results: All except one woman out of 37 women enrolled for the study had an un-eventful surgery with median duration of surgery [median 30 minutes; (range 30-55 minutes)], median hospital stay [(median 2 days) range 2-7 days], and minimal blood loss [median 50 ml (range 50-200 ml)]. There was one case of inadvertent cystotomy (diagnosed and repaired intra-operatively), and discharged in healthy condition on seventh post-operative day.Conclusions: NDVH is a safe option for hysterectomy (in women without pelvic organ prolapse) for benign indications even in rural India. It has been found to be associated with short hospital stay, minimal blood loss and short recovery time

Breast Cancer Detection

Breast Cancer is highly predominant in women in today’s world. It starts in the breast during the initial stages and spreads to other areas of the body after some period of time. Breast cancer is the second-largest disease leading to the death of women. The disease is curable if detected early enough. Breast Cancer Application monitors the abnormal growth of breast cells during the early stages. They are often diagnosed during the advanced stages of breast cancer. It is the second most diagnosed cancer in women, affecting one in every eight women. Our project comprises two modules, first consists of an application with user login and self-test examine section where and the second section consists of identifying benign and malignant cells. The second section will be used by doctors' side for the detection of abnormalities of breasts as early as possible by providing the user screening data set. It contains Machine Learning techniques for the classification of malignant and benign tumors. There are more treatment options and a better chance of survival. If breast cancer is detected during the early stages then there is a 93 percent of higher survival rate in the first five years

Nanoparticle-mediated targeting of phosphatidylinositol-3-kinase signaling inhibits angiogenesis

Objective: Dysregulation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a hallmark of human cancer, occurring in a majority of tumors. Activation of this pathway is critical for transformation and also for the angiogenic switch, which is a key step for tumor progression. The objective of this study was to engineer a PI3K inhibitor-loaded biodegradable nanoparticle and to evaluate its efficacy. Methods and results: Here we report that a nanoparticle-enabled targeting of the PI3K pathway results in inhibition of downstream Akt phosphorylation, leading to inhibition of proliferation and induction of apoptosis of B16/F10 melanoma. It, however, failed to exert a similar activity on MDA-MB-231 breast cancer cells, resulting from reduced internalization and processing of nanoparticles in this cell line. Excitingly, the nanoparticle-enabled targeting of the PI3K pathway resulted in inhibition of endothelial cell proliferation and tubulogenesis, two key steps in tumor angiogenesis. Furthermore, it inhibited both B16/F10- and MDA-MB-231-induced angiogenesis in a zebrafish tumor xenotransplant model. Conclusion: Our study, for the first time, shows that targeting of the PI3K pathway using nanoparticles can offer an attractive strategy for inhibiting tumor angiogenesis

Impact of genetic variants involved in the lipid metabolism pathway on progression free survival in patients receiving bevacizumab-based chemotherapy in metastatic colorectal cancer: a retrospective analysis of FIRE-3 and MAVERICC trials

Background: Antiangiogenic drug (AAD)-triggered oxygen and nutrient depletion through suppression of angiogenesis switches glucose-dependent to lipid-dependent metabolism. Blocking fatty acid oxidation can enhance AAD-mediated anti-tumor effects in colorectal cancer (CRC). Therefore, we hypothesised that genetic variants in the lipid metabolism pathway may predict clinical outcomes [overall response rate (ORR), overall survival (OS) and progression-free survival (PFS)] in metastatic CRC (mCRC) patients receiving bevacizumab-based first-line treatment. Methods: Genomic DNA from blood samples of patients enrolled in FIRE-3 (a global, randomised, open-label, phase 3 trial, between 2007-6-23 and 2012-9-19, discovery cohort: FOLFIRI/bevacizumab arm, n = 107; control cohort: FOLFIRI/cetuximab arm, n = 129) and MAVERICC (a global, randomised, open-label, phase II study, between 2011-8 and 2015-7, in United States, Canada, Estonia, Ireland, Switzerland, Norway, and Portugal. Validation cohort: FOLFIRI/bevacizumab arm, n = 163) trials, was genotyped using the OncoArray-500 K beadchip panel. The impact on OS and PFS of 17 selected SNPs in 7 genes involved in the lipid metabolism pathway (CD36, FABP4, LPCAT1/2, CPT1A, FASN, ACACA) was analysed using Kaplan-Meier curves, the log-rank test for univariate analyses and likelihood ratio tests of Cox proportional hazards regression parameters for multivariable analyses. ORR and SNP associations were evaluated using Chi-square or Fisher's exact tests. Findings: In the discovery cohort, patients with FASN rs4485435 any C allele (n = 21) showed significantly shorter PFS (median PFS: 8.69 vs 13.48 months) compared to carriers of G/G (n = 62) in multivariable (HR = 2.87; 95%CI 1.4-5.9; p = 0.00675) analysis. These data were confirmed in the validation cohort in multivariable analysis (HR = 2.07, 95%CI: 1.15-3.74; p = 0.02), but no association was observed in the cetuximab cohort of FIRE-3. In the comparison of bevacizumab vs cetuximab arm in FIRE-3, a significant interaction was shown with FASN rs4485435 (p = 0.017) on PFS. Interpretation: Our study demonstrates for the first time, to our knowledge, that FASN polymorphisms may predict outcome of bevacizumab-based treatment in patients with mCRC. These findings support a possible role of the lipid metabolism pathway in contributing to resistance to anti-VEGF treatment. Funding: This work was supported by the National Cancer Institute [P30CA 014089 to H.-J.L.], Gloria Borges WunderGlo Foundation, Dhont Family Foundation, Victoria and Philip Wilson Research Fund, San Pedro Peninsula Cancer Guild, Ming Hsieh Research Fund, Eddie Mahoney Memorial Research Fund, Shanghai Sailing Program (22YF1407000), China National Postdoctoral Program for Innovative Talents (BX20220084), China Postdoctoral Science Foundation (2022M710768), National Natural Science Foundation of China (82202892)

Central Composite Designed Formulation, Characterization and In-Vitro Cytotoxic effect of Erlotinib Loaded Chitosan Nanoparticulate System

© 2019 Elsevier B.V. The most common cause of deaths due to cancers nowadays is lung cancer. The objective of this study was to prepare erlotinib loaded chitosan nanoparticles for their anticancer potential. To study the effect of formulation variables on prepared nanoparticles using central composite design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using probe sonication technique. It was found that batch NP-7 has a maximum loading capacity and entrapment efficiency with a particle size (138.5 nm) which is ideal for targeting solid tumors. Analysis of variance was applied to the particle size, entrapment efficiency and percent cumulative drug release to study the fitting and the significance of the model. The batch NP-7 showed 91.57% and 39.78% drug release after 24 h in 0.1 N hydrochloric acid and Phosphate Buffer (PB) pH 6.8, respectively. The IC50 value of NP-7 evaluated on A549 Lung cancer cells was found to be 6.36 μM. The XRD of NP-7 displayed the existence of erlotinib in the amorphous pattern. The optimized batch released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using sonication technique with suitable particle size, entrapment efficiency and drug release. The formulated nanoparticles can be utilized for the treatment of lung cancer

Reporting trends, practices, and resource utilization in neuroendocrine tumors of the prostate gland: a survey among thirty-nine genitourinary pathologists

Background: Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods: Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results: A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion: There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland

Formulations of sustained release matrix tablets of Furosemide using natural and synthetic polymers

The primary benefit of a sustained release dosage form compared to a conventional dosage form, is the consistent drug plasma concentration and consequently uniform therapeutic effect. Matrix system are preferential because of their ease, patient compliance etc, than  traditional drug delivery which have several drawbacks like reiterated administration, variation in blood concentration level etc. The aim of the present research study was to develop and evaluate sustained release matrix tablets of furosemide using direct compression method using  natural  gummy  and  waxy  materials (Xanthan  gum, bees  wax)  and synthetic  polymers  (HPMC K4M). The matrix tablet formulations were prepared by using different drug: polymer ratios (1:1, 1:2 and 1:3). All formulations were assessed using micromeritics studies of powder blend and diverse physicochemical tests. All the physicochemical characters of the formulated tablets were within acceptable limits. The release pattern of the drug was viewed over a period of 12 hours and determined the amount of drug by the UV-Visible spectroscopic method. Dissolution data demonstrated that the formulated tablets with Xanthan gum and hydroxyl propyl methylcellulose (HPMC) provided sustained release of the drug up to 12 hrs. Therefore inexpensively it may be appropriate for the pharmaceutical industries to employ this kind of simple technologies for the expansion of advanced formulations. Hence, we conclude that the purpose of this study was to formulate a sustained release matrix tablet of furosemide using diverse polymers and their dissimilar proportions have been attained. Keywords: Furosemide, Direct compression, Natural, Synthetic polymers, Sustained release tablets

Evaluation of DNA Degradation Using Flow Cytometry Promising Tool for Postmortem Interval Determination

Over the years, there have been numerous formulas proposed for use in determining the postmortem interval (PMI); however, no method is all encompassing and absolute. Even so, very little research has been undertaken to determine if there is a viable correlation between the rate of DNA degradation and PMI, which can be calculated from analysis by flow cytometry. In this study, we analyzed the rate of DNA degradation of spleen and brain tissues from 15 cadavers over a 96-hour period of time at 2 temperature conditions, that is, 21 degrees C (room temperature) and 4 degrees C (refrigerator) to mimic summer and winter weather, respectively. The resulting data were used to form a pattern that correlates DNA degradation to cell death occurrence. Statistical analyses were performed to determine the significance of the relationship between PMI and DNA degradation. Moreover, in search of alternative reliable organs of interest for PMI estimation, the results demonstrate that the brain has lesser DNA degradation as compared with the spleen. Thus, the current study suggests that the brain can be an organ of choice for PMI studies, but more research is underway in this aspect