Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non –small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2

CONCLUSIONSAll 3 regimens were feasible for patients with advanced NSCLC and an ECOG performance status of 2. The addition of bevacizumab to pemetrexed increased the overall response rate. The efficacy of pemetrexed/carboplatin/bevacizumab (median PFS, 4.8 months) approached the prespecified study PFS goal of 5 months. Larger studies will be necessary to define the role of bevacizumab in addition to standard pemetrexed and carboplatin in this population. Cancer 2018. © 2018 American Cancer Society.
Source: Cancer - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research

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Cytosolic arginine sensor for mTORC1 subunits 1 and 2 (CASTOR1 and CASTOR2) inhibit the mammalian target of rapamycin complex 1 (mTORC1) upon arginine deprivation. mTORC1 regulates cell proliferation, survival, and metabolism and is often dysregulated in cancers, indicating that cancer cells may regulate CASTOR1 and CASTOR2 to control mTORC1 signaling and promote tumorigenesis. mTORC1 is the most effective therapeutic target of Kaposi sarcoma, which is caused by infection with the Kaposi sarcoma–associated herpesvirus (KSHV). Hence, KSHV-induced cellular transformation is a suitable model for investigating mTORC1 reg...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The presence of tumor-infiltrating T cells is associated with favorable patient outcomes, yet most pancreatic cancers are immunologically silent and resistant to currently available immunotherapies. Here we show using a syngeneic orthotopic implantation model of pancreatic cancer that Pik3ca regulates tumor immunogenicity. Genetic silencing of Pik3ca in KrasG12D/Trp53R172H-driven pancreatic tumors resulted in infiltration of T cells, complete tumor regression, and 100% survival of immunocompetent host mice. By contrast, Pik3ca-null tumors implanted in T cell–deficient mice progressed and killed all of the animals. Ad...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Glycosylation of immune receptors and ligands, such as T cell receptor and coinhibitory molecules, regulates immune signaling activation and immune surveillance. However, how oncogenic signaling initiates glycosylation of coinhibitory molecules to induce immunosuppression remains unclear. Here we show that IL-6–activated JAK1 phosphorylates programmed death-ligand 1 (PD-L1) Tyr112, which recruits the endoplasmic reticulum–associated N-glycosyltransferase STT3A to catalyze PD-L1 glycosylation and maintain PD-L1 stability. Targeting of IL-6 by IL-6 antibody induced synergistic T cell killing effects when combined...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Programmed death-1 receptor ligand 1 (PD-L1) is a promising therapeutic target in aggressive cancers. However, immune landscapes and cancer hallmarks of human PD-L1+ tumors as well as their roles in determining therapeutic efficacies are unknown. Here, we showed, in detailed studies of gene data regarding 9769 patients of 32 types of human cancers, that PD-L1 could not exclusively represent the IFN-γ signature and potentially signified proinflammatory myeloid responses in a tumor. PD-L1 heterogeneity endowed by local immune landscapes controlled cancer hallmarks and clinical outcomes of patients. Mechanically, NF-&ka...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Publication date: Available online 14 July 2019Source: Colloids and Surfaces A: Physicochemical and Engineering AspectsAuthor(s): Ying Wang, Jingwen Chen, Qianqian Han, Qiang Luo, Hongmei Zhang, Yanqing WangAbstractLentinan(LNT) has many kinds of pharmacological activities such as antioxidative activities, hypoglycemic effect, anti-hyperlipidemic effect and so on. Here, LNT was used as the skeleton material to couple with doxorubicin(DOX) by forming the LNT–DOX conjugates in order to enhance anticancer effects and reduce the systemic side effects of DOX. Based on the screening results, we observed that LNT can acted ...
Source: Colloids and Surfaces A: Physicochemical and Engineering Aspects - Category: Chemistry Source Type: research
This study describes the treatment patterns, effectiveness, and safety profile of Pem-Pt + Bev in patients with NS-NSCLC in China in clinical practice. METHODS: Data from eligible patients with advanced NS-NSCLC who received Pem-Pt with (136 patients) or without (97 patients) bevacizumab from January 2012 to March 2017 were retrospectively evaluated. The effectiveness outcomes included the assessment of progression-free survival (PFS) and objective response rate (ORR) in the overall population, the percentage of patients with pleural effusion or brain metastasis, as well as the percentage of patients receivi...
Source: Clinical Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Ther Source Type: research
Authors: Han S, Hong Y, Liu T, Wu N, Ye Z Abstract Objectives: To investigate the efficacy and safety of Bevacizumab (Bev) used in combination with paclitaxel and carboplatin (PC), compared with PC alone in patients with advanced non-small-cell lung cancer (NSCLC). Materials and Methods: We searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Chinese Biomedical Literature electronic databases, to identify randomized controlled trials of PC plus Bev versus PC alone for the treatment of NSCLC. The meta-analysis was performed using Reviewer Manager Version 5.3 software provided by the Co...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
ConclusionsThe addition of bevacizumab to erlotinib prolonged progression-free survival inEGFR mutation-positive NSCLC. Follow-up safety data were consistent with the known safety profiles of both erlotinib and bevacizumab in NSCLC; this combination appeared to be manageable, and treatment was well tolerated.JapicCTI-111390.
Source: Drug Safety - Category: Drugs & Pharmacology Source Type: research
Authors: Losanno T, Gridelli C Abstract Introduction - Lung cancer still represents the leading cause of death for cancer. About the 70% of diagnosis are in advanced-stage. Non-small-cell lung cancer (NSCLC) represents the 85% of all diagnosed lung cancers and non-squamous histology represents the 40% of all NSCLC. First-line therapies increase survival, control symptoms and improve quality of life, compared with best supportive care. It is crucial to choose a treatment with a low impact on patient's life considering the related toxicities. Areas covered - Adverse events (AEs) of first-line therapies for non-squamo...
Source: Expert Opinion on Drug Safety - Category: Drugs & Pharmacology Tags: Expert Opin Drug Saf Source Type: research
Vascular endothelial growth factor (VEGF) plays the most important role in regulating tumor-related angiogenesis and is often highly expressed in human cancers making it a preferred target for antitumor therapy [1,2]. With the introduction of VEGF inhibitors for cancer treatment, new class-specific adverse events (AEs) for these drugs have been observed, including perforations, bleeding, thromboembolic events, hypertension, and proteinuria [3,4]. Skin-related AEs are also often associated with the anti-VEGF small-molecule tyrosine kinase inhibitors sorafenib and sunitinib although these effects are not related directly to ...
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
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