2015013859.Despite major progress in the understanding of the pathophysiology and therapeutic options for common ageing-related musculoskeletal conditions (i.e. osteoporosis and associated fractures, sarcopenia and osteoarthritis), there is still a considerable proportion of patients who respond sub optimally to available treatments or experience adverse effects. Emerging microbiome research suggests that perturbations in microbial composition, functional and metabolic capacity (i.e. dysbiosis) are associated with intestinal and extra-intestinal disorders including musculoskeletal diseases. Besides its contributions to disease pathogenesis, the role of the microbiome is further extended to shaping individuals' responses to disease therapeutics (i.e. pharmacomicrobiomics). In this review, we focus on the reciprocal interactions between the microbiome and therapeutics for osteoporosis, sarcopenia and osteoarthritis. Specifically, we identify the effects of therapeutics on microbiome's configurations, functions and metabolic output, intestinal integrity and immune function, but also the effects of the microbiome on the metabolism of these therapeutics, which in turn, may influence their bioavailability, efficacy and side-effect profile contributing to variable treatment responses in clinical practice. We further discuss emerging strategies for microbiota manipulation as preventive or therapeutic (alone or complementary to available treatments) approaches for improving outcomes of musculoskeletal health and disease. Overexpression of cyclin-dependent kinase 7 (CDK7) is a well-known pathogenic feature of various malignancies and a sign of a more dismal prognosis. https://www.selleckchem.com/products/lb-100.html As relatively little is known about CDK7 in osteosarcoma, we elected to evaluate its expression, prognostic value, and function. We began by analyzing the publicly available data sets on CDK7 expression, including RNA sequencing data from the and the . The correlation between patient tissue CDK7 expression and their clinicopathological features and prognosis was assessed immunohistochemical staining of a unique tissue microarray constructed from osteosarcoma specimens. Furthermore, we analyzed CDK7 expression in osteosarcoma cell lines and tissues by Western blot. CDK7-specific siRNA and a highly-selective CDK7 inhibitor, BS-181, were applied to determine the function of CDK7 on osteosarcoma cell growth and proliferation. In addition, the effect of CDK7 inhibition on clonogenicity was evaluated using a clonogenic assay, and a 3D cell culture model was used to mimic CDK7 effects in an environment. Our results demonstrate that higher CDK7 expression significantly correlates with recurrence, metastasis, and shorter overall survival in osteosarcoma patients. Therapeutically, we show that CDK7 knockdown with siRNA or selective inhibition with BS-181 decreases proliferation and induces apoptosis of osteosarcoma cells. This study supports CDK7 overexpression as an independent predictor of poor prognosis and promising therapeutic target for osteosarcoma. This study supports CDK7 overexpression as an independent predictor of poor prognosis and promising therapeutic target for osteosarcoma.Small cell lung cancer (SCLC) is a highly proliferative, aggressive form of lung cancer that carries a poor prognosis. Recent approvals with new therapeutic options represent the first in more than a decade for SCLC. Lurbinectedin, a newly approved second-line option, is a synthetic alkaloid that covalently binds DNA, generating double-strand breaks, and disrupts DNA-protein interactions and RNA transcription. Lurbinectedin may also modulate the tumor microenvironment by inducing apoptosis of peripheral blood monocytes and tumor associated macrophages, decreasing expression of the inflammatory chemokine (C-C motif) ligand 2 (CCL2) and reducing tumor angiogenesis. A single-arm, open-label, basket trial included 105 patients with SCLC that had received one prior line of therapy. Patients received lurbinectedin 3.2 mg/m2 as an intravenous infusion every 3 weeks, resulting in a response rate of 35.2% and a disease control rate of 68.6%. The response rate was 45% among those with >90 days chemotherapy free interval (CTFI) and 22% in the resistant group (CTFI  less then  90 days). The median overall survival was 9.3 months. Myelosuppression is the most frequent clinically significant adverse event, particularly neutropenia; however, neutropenic fever occurred in only 5% of those in the SCLC cohort of the basket trial. Nausea and fatigue were also noted. The side effect profile compares favorably to topotecan, while a direct comparison of tolerability can be made between lurbinectedin versus topotecan or pegylated-liposomal doxorubicin from CORAIL, a randomized study for platinum-resistant/refractory ovarian cancer. A press release has reported the ongoing clinical trial for SCLC including combination lurbinectedin and doxorubicin versus topotecan or cyclophosphamide, doxorubicin, and vinblastine to be negative. The details may provide more insight at publication, and future trials will be important to further define the clinical utility of lurbinectedin. Lurbinectedin represents a new option in second-line SCLC. Although immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC), a lack of direct comparisons of various first-line treatments is clouding clinical decision-making. A network meta-analysis was conducted to compare current first-line treatments and identify the optimal regimen for patients with specific characteristics. PubMed, Embase, the Cochrane Central Register of Controlled Trials, Clinical Trials databases were searched from inception to 31 July 2020. Phase II/III randomized controlled trials (RCTs) comparing first-line treatments including chemotherapy, anti-angiogenesis, ICIs, and their combinations for previously untreated stage IIIB/IV or recurrent driver-gene wild-type NSCLC patients were included. Twenty-six RCTs were identified and included, involving 16,977 patients and a total of 18 regimens. ICI-containing treatments led to significantly prolonged overall survival (OS) compared with ICI-free treatments (0.82, 0.72-0.93). ICI plus chemotherapy had significantly longer progression-free survival (PFS; 0.