Search results for "ZOL"

Analysis of Antiproliferative and Chemosensitizing Effects of Sunitinib on Human Esophagogastric Cancer Cells: Synergistic Interaction With Vandetani…

2009

The receptor tyrosine kinases (RTKs), epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 1-3 (VEGFR1-3), are frequently expressed in gastric cancer and are putative therapeutic targets in this disease. We have investigated the anti-proliferative and chemosensitizing properties of the multitargeted small-molecule RTK inhibitors sunitinib and vandetanib in a panel of 4 human gastric and esophageal cancer cell lines. In the 1st instance, the expression of potential targets of these small-molecule inhibitors was examined by reverse transcriptase-polymerase chain reaction, western blotting, and flow cytometry. EGFR mRNA and protein was detected in all cases, …

Transcriptome and computational analysis assess the anti-tubulin activity of [1,2]oxazole derivatives in lymphoma

2022

Carboxyamidotriazole inhibits cell growth of imatinib-resistant chronic myeloid leukaemia cells including T315I Bcr-Abl mutant by a redox-mediated me…

2010

Mutation of the Bcr–Abl oncoprotein is one of most frequent mechanisms by which chronic myelogenous leukemia (CML) cells become resistant to imatinib. Here, we show that treat- ment of cell lines harbouring wild type or mutant BCR–ABL with carboxyamidotriazole (CAI), a calcium influx and signal transduction inhibitor, inhibits cell growth, the expres- sion of Bcr–Abl and its downstream signalling, and induces apoptosis. Moreover, we show that CAI acts by increasing intracellular ROS. Clinically significant, CAI has also inhibitory effects on T315I Bcr–Abl mutant, a mutation that causes CML cells to become insensitive to imatinib and second generation abl kinase inhibitors.

Abstract PS10-16: Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatm…

2021

Abstract Background: In MONALEESA-3 and MONALEESA-7 trials, ribociclib (RIB, a selective CDK4/6 inhibitor) in combination with endocrine therapy (aromatase inhibitor [AI] or fulvestrant [FUL]) demonstrated a significant prolongation of overall survival among patients with breast cancer (BC), regardless of menopausal status and treatment-line. In the premenopausal or perimenopausal women, RIB + AI/FUL should be combined with a luteinizing hormone-releasing hormone agonist. The real-world evidence for the effectiveness, safety, and tolerability of RIB + AI/FUL in the routine clinical practice is needed to support the use of this combination. Methods: RIBANNA is a prospective, non-intervention…

Abstract PS11-11: Targeted safety events from a phase I/Ib study evaluating GDC-0077 alone and in combination with endocrine therapy (ET) ± palbocicl…

2021

Abstract Background Activating mutations in PIK3CA, encoding the p110α subunit of phosphatidylinositol 3-kinase (PI3K) occur in ~40% of HR+/HER2- BCs. GDC-0077, a PI3Kα-selective inhibitor and mutant PI3Kα degrader, is being developed as an anticancer agent. A phase I/Ib study of GDC-0077 alone and combined with other therapies is ongoing in pts with locally advanced or metastatic PIK3CAmut, HR+/HER2- mBC (NCT03006172). Targeted safety events are presented here. Methods Safety was assessed via NCI-CTCAE v4 for GDC-0077 administered alone (Arm A), with letrozole and palbo (Arm B), with letrozole (Arm C), with fulvestrant (Arm D), or with fulvestrant and palbo (Arm E, plus metformin in Arm F …

Cetuximab-induced skin exanthema: Improvement by a reactive skin therapy

2010

More than 80% of patients treated with cetuximab develop an acneiform follicular skin exanthema. Grade 3 exanthema develops in 9-19% of these cases, bearing the risk of cetuximab dose-reduction or cessation. We retrospectively analysed a cohort of 20 patients treated with cetuximab and an in-house reactive skin protocol upon development of an exanthema. The reactive skin protocol was built up as follows: grade 1 exanthema: topical cleansing syndet (Dermowas®) + topical metronidazole cream (Rosiced®); grade 2 exanthema: grade 1 treatment + oral minocycline 50 mg twice per day; grade 3 exanthema: grade 2 treatment + topical corticoid (Dermatop®) + topical nadifloxacin (Nadixa®). As soon as a …

Cyclooxygenase-2 inhibition induces apoptosis signaling via death receptors and mitochondria in hepatocellular carcinoma.

2006

AbstractInhibition of cyclooxygenase (COX)-2 elicits chemopreventive and therapeutic effects in solid tumors that are coupled with the induction of apoptosis in tumor cells. We investigated the mechanisms by which COX-2 inhibition induces apoptosis in hepatocellular carcinoma (HCC) cells. COX-2 inhibition triggered expression of the CD95, tumor necrosis factor (TNF)-R, and TNF-related apoptosis-inducing ligand (TRAIL)-R1 and TRAIL-R2 death receptors. Addition of the respective specific ligands further increased apoptosis, indicating that COX-2 inhibition induced the expression of functional death receptors. Overexpression of a dominant-negative Fas-associated death domain mutant reduced COX…

Adherence to ruxolitinib, an oral JAK1/2 inhibitor, in patients with myelofibrosis: interim analysis from an Italian, prospective cohort study (ROMEI…

2021

ROMEI, a prospective, observational study in patients with myelofibrosis receiving the oral JAK1/2 inhibitor ruxolitinib in real-world practice, assesses treatment adherence based on the 8-item Morisky Medication Adherence Scale (MMAS-8). Here, we present MMAS-8 results at week 24. Overall, 101 of 188 evaluable patients completed the questionnaire at every visit (full completers). Mean (±standard deviation) total MMAS-8 scores remained stable from week 4 to week 24 in the overall population (7.54 ± 0.77 and 7.67 ± 0.70, respectively) and full completers (7.53 ± 0.79 and 7.67 ± 0.73, respectively). Rates of low (MMAS-8 ˂6) or medium (MMAS-8 ≥ 6 to ˂8) adherence were 25–40% and 26–36%, respec…

2021

IntroductionImmune checkpoint inhibitors (ICI) are increasingly being used to treat numerous cancer types. Together with improved recognition of toxicities, this has led to more frequent identification of rare immune-related adverse events (irAE), for which specific treatment strategies are needed. Neutropenia is a rare hematological irAE that has a potential for a high mortality rate because of its associated risk of sepsis. Prompt recognition and timely treatment of this life-threatening irAE are therefore critical to the outcome of patients with immune-related neutropenia.MethodsThis multicenter international retrospective study was conducted at 17 melanoma centers to evaluate the clinic…

Preexisting musculoskeletal burden and its development under letrozole treatment in early breast cancer patients

2019

One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statis…