MY11 exerts antitumor effects through activation of the NF- κB/PUMA signaling pathway in breast cancer
AbstractBreast cancer is the most common malignancy in women worldwide, and the discovery of new effective breast cancer therapies with lower toxicity is still needed. We screened a series of chalcone derivatives and found that MY11 ((E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(4-piperazinylphenyl) prop-2-en-1-one) had the strongest anti-breast cancer activity. MY11 inhibited the growth of MDA-MB-231 and MCF-7 breast cancer cells by arresting the cell cycle and promoting apoptosis, through regulation of the cell cycle and apoptosis-related proteins. PDTC (Pyrrolidinedithiocarbamate ammonium), a specific inhibitor of the NF- κ...
Source: Investigational New Drugs - June 27, 2022 Category: Drugs & Pharmacology Source Type: research
A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors
AbstractClaudin6(CLDN6) is a tight junction protein of claudin-tetraspanin family and is of the earliest molecules expressed in embryonic epithelium. CLDN6 is frequently aberrantly expressed in testicular germ-cell tumors(GCT). ASP1650 is a chimeric-mouse/human-IgG1 antibody directed against CLDN6. Two-part, open-label, phase-II trial investigating ASP1650 in patients with relapsed/refractory GCT and no curable options. Part1 was a safety lead-in to establish the recommended-phase-II-dose(RP2D). Part2 was a phase-II study designed to evaluate the antitumor effects of ASP1650. CLDN6 expression was centrally assessed on arch...
Source: Investigational New Drugs - June 27, 2022 Category: Drugs & Pharmacology Source Type: research
Genetic variations in the ATP-binding cassette transporter ABCC10 are associated with neutropenia in Japanese patients with lung cancer treated with nanoparticle albumin-bound paclitaxel
In this study, we investigated whether the rs2125739 variant could affect paclitaxel (PTX) cytotoxicity in lung cancer cell lines. We also investigated the effect of rs2125739 on the efficacy and safety of nanoparticle albumin-bound PTX (nab-PTX) in clinical practice. The association between rs2125739 genotypes and the 50% inhibitory concentration (IC50) of PTX was investigated in 18 non-small cell lung cancer (NSCLC) cell lines, HeLa cells, and genome-edited HeLa cells. Next, blood samples from 77 patients with NSCLC treated with carboplatin plus nab-PTX were collected and analyzed for six SNPs, including rs2125739. The c...
Source: Investigational New Drugs - June 27, 2022 Category: Drugs & Pharmacology Source Type: research
Efficacy and safety of amrubicin monotherapy after atezolizumab plus carboplatin and etoposide in patients with relapsed small-cell lung cancer
This study examined the activity and safety of amrubicin monotherapy among relapsed small-cell lung cancer (SCLC) patients who had previously been treated with atezolizumab plus carboplatin and etoposide (AteCE). This retrospective study evaluated patients with relapsed SCLC who were treated with previously AteCE combination therapy followed by amrubicin monotherapy between August 2019 and May 2021. Clinical efficacy and toxicity were analyzed. Overall, 40 patients were included: 12 and 28 patients had sensitive and refractory relapse, respectively. The response rate was 32.5% (25.0% in the sensitive group and 35.7% in the...
Source: Investigational New Drugs - June 24, 2022 Category: Drugs & Pharmacology Source Type: research
Pulmonary granulomatous inflammation after ceritinib treatment in advanced ALK-rearranged pulmonary adenocarcinoma
SummaryCeritinib is a new anaplastic lymphoma kinase (ALK) inhibitor that has shown greater potency in patients with advanced ALK-rearranged non-small cell lung cancer, including those who had disease progression in crizotinib treatment. Here we reported, after several months of ceritinib treatment, two patients with advanced ALK-rearranged pulmonary adenocarcinoma exhibited a spectrum of respiratory symptoms like cough and dyspnea, with significantly higher inflammatory indicators. Chest computed tomography (CT) showed multiple bilateral and peripheral lesions in lungs. The prior considerations taken into account were dis...
Source: Investigational New Drugs - June 21, 2022 Category: Drugs & Pharmacology Source Type: research
A comprehensive analysis of the microbiota composition and host driver gene mutations in colorectal cancer
AbstractStudies of both, microbiota and target therapy associated with gene mutations in colorectal cancer, (CRC) have attracted increasing attention. However, only a few of them analyzed the combined effects on CRC. we analyzed differences in intestinal microbiota of 44 colorectal cancer patients and 20 healthy controls (HC) using 16S rRNA gene sequencing of fecal samples. For 39 of the CRC patients, targeted Next Generation Sequencing (NGS) was carried out at formalin fixed paraffin embedded (FFPE) samples to identify somatic mutation profiles. Compared to the HC group, the microbial diversity of CRC patients was signifi...
Source: Investigational New Drugs - June 21, 2022 Category: Drugs & Pharmacology Source Type: research
The efficacy of transarterial chemoembolization in downstaging unresectable hepatocellular carcinoma to curative therapy: a predicted regression model
AbstractPatients with hepatocellular carcinoma (HCC) outside Milan criteria (MC) may be candidates for curative therapy after successful downstaging. We aimed to identify the predictors of successful downstaging of unresectable HCC in patient by transarterial chemoembolization (TACE) outside MC. We performed a retrospective study on patients with unresectable HCC outside MC who received downstaging with TACE. Clinical and laboratory variables were recorded. We identified 101 patients with unresectable HCC who underwent initial TACE, who formed the derivation set of this study. Thirty patients who treated by TACE with the s...
Source: Investigational New Drugs - June 20, 2022 Category: Drugs & Pharmacology Source Type: research
ZL-n-91, a specific Phosphodiesterase-4 inhibitor, suppresses the growth of triple-negative breast cancer
AbstractTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that frequently develops resistance to chemotherapy. A new approach to treating TNBC is required to improve patient survival. Phosphodiesterase-4 (PDE4) is an enzyme that is predominantly involved in the modulation of intracellular signaling mediated by cAMP. Although the efficacy of PDE4 inhibitors in several human inflammatory diseases is well documented, their clinical utility has been limited by side effects, including nausea and emesis. Recently, PDE4 has been used as a potential therapeutic target for different cancer types. In the...
Source: Investigational New Drugs - June 8, 2022 Category: Drugs & Pharmacology Source Type: research
A novel SLC8A1/LINC01913 intergenic region-ALK fusion identified by NGS and validated by IHC and FISH in a stage IIB lung adenocarcinoma patient who remains relapse-free during the treatment of crizotinib: a case report
This report provided a valuable treatment plan for early lung adenocarcinoma patients with high risks to prevent a postoperative recurrence. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 6, 2022 Category: Drugs & Pharmacology Source Type: research
Dacomitinib overcomes afatinib-refractory carcinomatous meningitis in a lung cancer patient harbouring EGFR Ex.19 deletion and G724S mutation; a case report
AbstractIt has been reported that the efficacy of EGFR-TKI is predicted, not by which exon of theEGFR gene is mutated, but by the structural change in the EGFR protein due to the mutation. Here, we present anEGFR-mutated lung cancer patient with a 13-year history of anticancer treatment, in whichEGFR ex.19 deletion (E746_S752 > V) and G724S mutations were detected by liquid biopsy during 12th line afatinib treatment, and switching to dacomitinib showed improvement of cancerous meningitis. We choose dacomitinib as 14th line chemotherapy based on ex.19 deletion and G724S mutant EGFR structure and its penetration rat...
Source: Investigational New Drugs - June 3, 2022 Category: Drugs & Pharmacology Source Type: research
A lung adenocarcinoma patient harboring MET c. 3028 + 2 T & gt;A variant sensitive to crizotinib treatment
AbstractSeveral studies have reported that patients harboring MET-ex14 skipping benefit from MET tyrosine kinase inhibitors (TKIs) such as crizotinib, however, the overall response of crizotinib was 32% in these patients. Therefore, the clinical outcome of patients harboring different MET 14 skipping subtypes are worthy to be concern. Based on NGS analysis, we described a lung adenocarcinoma patient harboring a MET c.3028 + 2 T > A mutation which was predicted to lead to MET-ex14 skipping. Moreover, we performed IHC and qPCR to verify this variant. Then the patient treated with crizotinib and achieved good th...
Source: Investigational New Drugs - May 12, 2022 Category: Drugs & Pharmacology Source Type: research
Identifification of a novel LDLR-RET Fusion in Lung Adenocarcinoma
ConclusionsThis novel form of RET fusion in NSCLC is reported for the first time worldwide, offering a new treatment option for the patient with the possibility of using RET-selective inhibitors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 7, 2022 Category: Drugs & Pharmacology Source Type: research
Autoimmune hemolytic anemia in patients with relapsed Hodgkin ’s lymphoma after treatment with penpulimab, a monoclonal antibody against programmed death receptor-1
SummaryIn August 2021, penpulimab, an anti-programmed cell death 1 (PD-1) monoclonal antibody, was approved in China for the treatment of adult patients with relapsed or refractory classic Hodgkin ’s lymphoma who completed at least second-line chemotherapy. Penpulimab is currently in clinical trials in China and Australia for the treatment of nasopharyngeal cancer and non-small cell lung cancer. Several clinical studies have shown that penpulimab is safe and effective, and no immune-related adverse events (irAEs) above grade 3 were observed. A 60-year-old woman with relapsed Hodgkin’s lymphoma developed nausea and fati...
Source: Investigational New Drugs - May 3, 2022 Category: Drugs & Pharmacology Source Type: research
Exportin-1 is critical for cell proliferation and survival in adult T cell leukemia
This study aimed to investigate the potential of exportin-1 (XPO1), which mediates nuclear export of cargos, as a target in ATL. RT-PCR and western blotting were performed to determine XPO1 expression. We evaluated XPO1 ’s effects on cell proliferation and viability through WST-8 assays, cell cycle and apoptosis via Hoechst 33342 staining and flow cytometry, and intracellular signaling cascades using western blotting. XPO1 expression was upregulated in HTLV-1-infected T cells. XPO1 knockdown reduced cell prolifer ation. XPO1 inhibitor KPT-330 also reduced proliferation, increased DNA damage, and induced G1 cell cycle arr...
Source: Investigational New Drugs - April 28, 2022 Category: Drugs & Pharmacology Source Type: research
Lenvatinib combined with nivolumab in advanced hepatocellular carcinoma-real-world experience
AbstractLenvatinib, a multi-tyrosine kinase inhibitor that inhibits vascular endothelial growth factor and fibroblast growth factor receptors pathway, activated the immune response in tumor microenvironment. However, the combination of lenvatinib and anti-PD-1 has been reported in early phase studies. Hence, this study aims to explore the efficacy and toxicity of lenvatinib combined with nivolumab in the real-world setting. Advanced HCC patients who underwent lenvatinib combined with nivolumab (L + N group) treatment at Taipei Veterans General Hospital (Taipei, Taiwan) were reviewed between January 2016 and December 2...
Source: Investigational New Drugs - April 28, 2022 Category: Drugs & Pharmacology Source Type: research
