Study of growth-improving and sporophore-inducing endobacteria isolated from Pleurotus pulmonarius.

Several Pleurotus species (oyster mushrooms) are commercially cultivated in India owing to the favorable tropical agro-climatic conditions. However, there are only a few studies on the microbiome of mushrooms, especially oyster mushrooms. The aim of this study was to assess the effect of endobacteria on mycelial growth, spawning, sporophore development, and proximate composition of P. pulmonarius. We isolated several bacterial strains from the sporophores of P. pulmonarius and assessed the in vitro production of indole acetic acid, ammonia, and siderophores. The selected bacteria were individually supplemented with spawn, substrate, or both for sporophore production. Three of 130 isolates were selected as mycelial growth-promoting bacteria in both solid and submerged fermentation. These bacterial isolates were identified through Gram staining, biochemical characterization, and 16S rRNA sequencing. Isolate PP showed 99.24% similarity with Priestia paraflexa, whereas isolates PJ1 and PJ2 showed 99.78% and 99.65% similarities, respectively, with Rossellomorea marisflavi. The bacterial supplementation with spawn, substrate, or both, increased the biological efficiency (BE) and nutrient content of the mushrooms. The bacterial supplementation with substrate augmented BE by 64.84%, 13.73%, and 27.13% using PJ2, PP, and PJ1, respectively; under similar conditions of spawn supplementation, BE was increased by 15.24%, 47.30%, 48.10%, respectively. Overall, the supplementation of endobacteria to improve oyster mushroom cultivation may open a new avenue for sustainable agricultural practices in the mushroom industry.

A phase I trial of palbociclib and bosutinib with fulvestrant in patients with metastatic hormone receptor positive and HER2 negative (HR+ HER2-) breast cancer refractory to an aromatase inhibitor and a CDK4/6 inhibitor.

Standard treatment for metastatic hormone positive (HR+) breast cancer includes a combination of a CDK4/6 inhibitor and antiestrogen therapy. Despite durable responses, eventual endocrine resistance results in disease progression. The Src/Abl pathway has been shown to mediate endocrine resistance in breast cancer, thus providing a promising target for novel therapies. Bosutinib is a tyrosine kinase inhibitor that targets the Src/Abl pathway, which has been studied in hematologic malignancies. Preclinical data suggests that the addition of bosutinib to a CDK4/6 inhibitor and antiestrogen therapy has the potential to reverse endocrine resistance. This is a phase I, single arm, open-label clinical trial in which we evaluate the combination of palbociclib and fulvestrant with bosutinib in metastatic HR+ breast cancer. Patients with confirmed advanced HR+/HER2- breast cancer who have received no more than three lines of chemotherapy and have progressed on at least one aromatase inhibitor and one CDK4/6 inhibitor will be enrolled. Participants will be given a combination of palbociclib, fulvestrant and bosutinib over 28-day cycles. The primary objective of this study is to assess the safety and tolerability of bosutinib in combination with palbociclib and fulvestrant in the study population. Secondary objectives are to 1) determine the anti-tumor effect of this therapeutic combination by assessing overall response rate (ORR) and clinical benefit rate (CBR) after 6 months of treatment, 2) to determine the clinical pharmacology parameters of bosutinib in this regimen, and 3) to build a tissue repository at Georgetown Lombardi Comprehensive Cancer Center for further translational study.

TKIs beyond immunotherapy predict improved survival in advanced HCC.

PURPOSE: For patients with advanced HCC, predictors of immunotherapy response are scarce, and the benefits of tyrosine kinase inhibitor (TKI) treatment after immunotherapy are unclear. We explored whether clinical features, such as target lesion response, immune-mediated toxicity, or subsequent TKI therapy predict immunotherapy response. METHODS: We retrospectively studied 77 patients with advanced HCC receiving immunotherapy. Patient characteristics and outcomes were assessed using various statistical methods, including the log-rank test and Kaplan-Meier methods. Cox proportional hazard modeling was used for multivariable survival analysis. RESULTS: For all patients, median overall survival (mOS) was 13 months (95% CI 8-19), and median progression-free survival (mPFS) was 6 months (95% CI 4-10). Patients with partial response (PR) and stable disease (SD) compared to progressive disease (PD) had prolonged mPFS (27 vs. 5 vs. 1 month(s), p < 0.0001) and mOS (not met vs. 11 vs. 3 months, p < 0.0001). Patients with vs. without immune-mediated toxicities trended towards longer mPFS (9 vs. 4 months p = 0.133) and mOS (17 vs. 9 months; p = 0.095). Patients who did vs. did not receive a tyrosine kinase inhibitor (TKI) after immunotherapy had a significantly improved mOS (19 vs. 5 months, p = 0.0024)). Based on multivariate modeling, the hazard ratio (HR) of overall survival (OS) of patients receiving TKI vs. no TKI was 0.412 (p = 0.0043). CONCLUSION: We show that disease control predicts prolonged mOS and mPFS. Furthermore, TKI therapy administered after immunotherapy predicts prolonged mOS in patients with advanced HCC.

Race & sex disparities related to low-dose computed tomography lung cancer screening eligibility criteria: A lung cancer cases review.

INTRODUCTION: The United States Preventive Services Task Force (USPSTF) recommendations do not account for race and sex differences in lung cancer risk. We compared the sensitivity for finding lung cancer cases eligible for lung cancer screening (LCS) by USPSTF 2013 recommendations versus the PLCOm2012 model at an equivalent threshold. METHODS: Using Georgetown University Hospital tumor registry, we identified lung cancer cases (≥55 years old) between 2014 and 2018. Medical chart review collected age, sex, race, education, smoking, and clinical characteristics. We compared the percentage meeting eligibility criteria overall, and by race and sex. RESULTS: The cases (N = 447) were 36.6% Black and 52.6% female. The PLCOm2012 and USPSTF 2013 criteria identified 71.4% and 45.6% of cases, respectively (p < 0.0001). This difference was consistent across race and sex sub-groups (p < 0.0001). The PLCOm2012 was more sensitive than the USPSTF in Blacks (69.9% vs. 46.6%, p < 0.0001) and in women (69.8% vs. 41.3%, p < 0.0001). The USPSTF had poor sensitivity for both race groups (Black 46.6%, White 45.9%, p = 0.886) and had lower sensitivity in women vs. men (41.3% vs. 51.4%, p = 0.032). The PLCOm2012 had higher sensitivities in women and men, and difference between sexes was not significant (69.8% vs. 72.6%, p = 0.506). CONCLUSIONS: Compared to the USPSTF 2013 recommendations, the PLCOm2012 model selected a larger proportion of lung cancer cases in all race-sex strata and removed the sex disparity observed for the USPSTF. The PLCOm2012 risk model could be used to identify those who will benefit from LCS.

Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition?

Biliary tract cancers (BTCs) are a heterogeneous group of malignancies that make up ~7% of all gastrointestinal tumors. It is notably aggressive and difficult to treat; in fact, >70% of patients with BTC are diagnosed at an advanced, unresectable stage and are not amenable to curative therapy. For these patients, chemotherapy has been the mainstay treatment, providing an inadequate overall survival of less than one year. Despite the boom in targeted therapies over the past decade, only a few targeted agents have been approved in BTCs (i.e., IDH1 and FGFR inhibitors), perhaps in part due to its relatively low incidence. This review will explore current data on PARP inhibitors (PARPi) used in homologous recombination deficiency (HRD), particularly with respect to BTCs. Greater than 28% of BTC cases harbor mutations in genes involved in homologous recombination repair (HRR). We will summarize the mechanisms for PARPi and its role in synthetic lethality and describe select genes in the HRR pathway contributing to HRD. We will provide our rationale for expanding patient eligibility for PARPi use based on literature and anecdotal evidence pertaining to mutations in HRR genes, such as RAD51C, and the potential use of reliable surrogate markers of HRD.

Role of Plasmid in Pesticide Degradation and Metal Tolerance in Two Plant Growth-Promoting Rhizobacteria Bacillus cereus (NCIM 5557) and Bacillus safensis (NCIM 5558).

Disha A (Bacillus cereus) and Disha B (Bacillus safensis) were isolated from pesticide-infested agricultural field and showed tolerance against pesticides, heavy metals, and antibiotics. The isolates exhibited PGPR activities in vitro as well as in field conditions in lentil (Lens culinaris) and cow pea (Vigna unguiculata). Both the Bacillus species could not be grown in mineral salt medium but efficiently grown in the media supplemented with pesticide (imidacloprid/carbendazim) demonstrating the utilization of pesticide as carbon/nitrogen source. The HPLC studies exhibited the pesticide (imidacloprid/carbendazim) degradation by both the bacteria. B. safensis showed better degradation of carbendazim (88.93%) and imidacloprid (82.48%) than that of B. cereus 78.07% and 49.12%, respectively. The bacterial isolates showed high concentration of heavy metal tolerance viz. lead, molybdenum, cadmium, copper, cobalt, and zinc, except mercury. Both the bacteria possessed single plasmid. The plasmid-cured isolates of B. cereus did not tolerate any pesticide, whereas that of B. safensis tolerated all the pesticides, like wild strains. The plasmid curing experiments did not affect the heavy metal tolerance ability of both the bacteria indicating the genomic nature of heavy metal tolerance genes, whereas pesticide resistance genes are plasmid-dependent in B. cereus but genomic in B. safensis.

Probiotics and gastrointestinal conditions: An overview of evidence from the Cochrane Collaboration.

Alterations in the composition of the gut microbiota are associated with a number of gastrointestinal (GI) conditions, including diarrhea, inflammatory bowel diseases (IBD), and liver diseases. Probiotics, live microorganisms that may confer a health benefit to the host when consumed, are commonly used as a therapy for treating these GI conditions by means of modifying the composition or activity of the microbiota. The purpose of this review was to summarize the evidence on probiotics and GI conditions available from Cochrane, a nonprofit organization that produces rigorous and high-quality systematic reviews of health interventions. Findings from this review will help provide more precise guidance for clinical use of probiotics and to identify gaps in probiotic research related to GI conditions.