Search results for "Solid tumor"
showing 10 items of 52 documents
Bortezomib: a new pro-apoptotic agent in cancer treatment.
2010
Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IkappaB breakdown and the related stabilization of NFkappaB, thus preventing its translocation to the nucleus for the activation of downstream pathways. Bortezomib is the only drug in this class which has been approved for clinical use. It has shown an efficient antitumor effect in a phase III clinical trial (APEX) involving relapsed multiple myeloma patients. Response rate, time to progression and overall survival have been improved…
From the covalent linkage of drugs to novel inhibitors of ribonucleotide reductase: synthesis and biological evaluation of valproic esters of 3'-C-me…
2014
We synthesized a series of serum-stable covalently linked drugs derived from 3'-C-methyladenosine (3'-Me-Ado) and valproic acid (VPA), which are ribonucleotide reductase (RR) and histone deacetylase (HDAC) inhibitors, respectively. While the combination of free VPA and 3'-Me-Ado resulted in a clear synergistic apoptotic effect, the conjugates had lost their HDAC inhibitory effect as well as the corresponding apoptotic activity. Two of the analogs, 2',5'-bis-O-valproyl-3'-C-methyladenosine (A160) and 5'-O-valproyl-3'-C-methyladenosine (A167), showed promising cytotoxic activities against human hematological and solid cancer cell lines. A167 was less potent than A160 but had interesting featu…
Imaging of Gastrointestinal Stromal Tumors: From Diagnosis to Evaluation of Therapeutic Response
2016
Once considered an obscure tumor entity with poor prognosis, gastrointestinal stromal tumors (GISTs) are nowadays recognized as the most common mesenchymal tumors of the alimentary tract. GISTs differ from other mesenchymal neoplasms at pathology since 90% of them exhibit strong immunohistochemical staining for KIT, a tyrosinase kinase growth factor receptor. In the early 2000s, the ability of imatinib mesylate, a tyrosine kinase inhibitor, to inhibit KIT established a new paradigm for cancer treatment. A reduction in lesion size may not be observed or may appear many months after therapy; thus, tumor response criteria alternative to the Response Evaluation Criteria in Solid Tumors were dev…
Rapid Access to Polyfunctional Lipids with Complex Architecture via Oxyanionic Ring-Opening Polymerization
2011
Polymer-coated liposomes, particularly poly(ethylene glycol) (PEG)-substituted liposomes, have emerged as long-circulating carrier systems for drug delivery and diagnostic purposes. A rapid synthesis of three different types of multifunctional lipids with structurally diverse hydrophilic, polyether-based architectures via one- or two-pot approaches is described. Architectural variation is achieved by the combination of different oxyanionic polymerization strategies and various glycidyl ether building units. Branched polyglycerol lipids have been prepared via cholesterol- or 1,2-bis-n-alkyl glyceryl ether-initiated, oxyanionic ring-opening polymerization (ROP) of protected glycidyl ethers an…
Phase I study of OM-174, a lipid A analogue, with assessment of immunological response, in patients with refractory solid tumors.
2013
International audience; BACKGROUND: Lipids A, the lipophilic partial structure of lipopolysaccharides, induce regression of several tumor types in animal models. Rather than exerting direct cytotoxic effect, these compounds trigger the immune system which in turn stimulates secretion of cytokines, and activates the inducible nitric oxide synthase, as well as immune cell infiltration of tumors. OM-174 is an analogue of lipid A with dual action on toll-like receptors 2 and 4. In an experimental model of peritoneal carcinomatosis induced in BDIX rats by intraperitoneal injection of syngeneic PROb colon cancer cells, it induced a complete regression of tumors. The present phase I trial was cond…
Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors
2020
Inhibidor d'AKT; Càncer avançat; Fase I Inhibidor de AKT; Cáncer avanzado; Fase I AKT inhibitor; Advanced cancer; Phase I Background This phase Ib study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of the oral AKT inhibitor ipatasertib and chemotherapy or hormonal therapy in patients with advanced or metastatic solid tumors to determine combined dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase II doses and schedules. Patients and methods The clinical study comprised four combination treatment arms: arm A (with docetaxel), arm B [with mFOLFOX6 (modified leucovorin, 5-fluorouracil, and oxaliplatin)], arm C (with paclitaxel), and …
Vinflunine in Metastatic Urothelial Carcinoma of the Bladder in Progression after a Platinum-Containing Regimen
2019
<b><i>Background:</i></b> Vinflunine is a microtubule inhibitor of the vinca alkaloid class approved for the treatment of urothelial bladder carcinoma after a platinum-containing regimen. <b><i>Methods:</i></b> To evaluate the effectiveness of vinflunine, we enrolled 80 subjects with a histologically confirmed diagnosis of metastatic urothelial bladder carcinoma that had previously undergone chemotherapy with a platinum-containing regimen and had measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). The patients (<i>n</i> = 80) received vinflunine (Javlor®) every 3 weeks at 320 mg/m<sup>2&…
Dynamic contrast-enhanced MRI parameters as biomarkers for the effect of vatalanib in patients with non-small-cell lung cancer.
2014
ABSTRACT: Aims: To assess the utility of dynamic contrast-enhanced MRI parameters in the demonstration of early antiangiogenic effects and as prognostic biomarkers in second-line treatment of advanced-stage non-small-cell lung cancer with vatalanib. Patients & methods: The transfer constant (Ktrans) and the initial area under the contrast concentration–time curve at 60 s (AUC60) were assessed in 46 patients. Changes were compared with response evaluation from computed tomography imaging and Response Evaluation Criteria In Solid Tumors guidelines. Results: Statistically significant mean reductions in Ktrans (38.4%; p < 0.0001) and AUC60 (24.9%; p < 0.0001) were found at day 2. Af…
Evaluating the incidence of pathological complete response in current international rectal cancer practice: the barriers to widespread safe deferral …
2018
INTRODUCTION: The mainstay of management for locally advanced rectal cancer is chemoradiotherapy followed by surgical resection. Following chemoradiotherapy, a complete response may be detected clinically and radiologically (cCR) prior to surgery or pathologically after surgery (pCR). We aim to report the overall complete pathological response (pCR) rate and the reliability of detecting a cCR by conventional pre-operative imaging.METHODS: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients treated by elective rectal resection were included. A pCR was defined as a ypT0 N0 EMVI negative primary tumour; a partial response represented any r…
Nonconventional Doses of Somatostatin Analogs in Patients With Progressing Well-Differentiated Neuroendocrine Tumor
2020
Abstract Purpose To evaluate the antiproliferative activity and safety of nonconventional high doses of somatostatin analogs (HD-SSA) in patients with well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NET) with radiological disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria on a previous treatment. Methods A retrospective analysis of prospectively maintained databases from 13 Italian NET-dedicated centers was performed. Main inclusion criteria were: well-differentiated G1 or G2 GEP-NET, progressive disease on a previous treatment, and subsequent treatment with HD-SSA (either by increased administered dose [dose intensity] or…