True

Gregory, R. K.; Smith, Ian

doi:10.1054/bjoc.2000.1203

Cited by 93 publications

(16 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, microtubules also assist in stabilizing the invadopodium core, which is used to generate a protrusive force during elongation of invadopodia [10] . Vinorelbine tartrate and paclitaxel target microtubules in opposing approaches; vinorelbine prevents their assembly by binding to tubules and inhibiting their polymerization [58] , while paclitaxel hyperstabilizes microtubules and hence prevents their disassembly [59] . In the case of paclitaxel, hyper-stabilization impedes the ability of microtubules to shorten and lengthen, which is necessary for their role as a molecule transport highway to the cell membrane [60] , whereas vinorelbine hinders microtubule assembly and prevents a phenomenon known as “treadmilling” that involves active dynamics and microtubule lengthening through the addition of tubulin subunits at one end of the microtubule [61] .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs

Whitehead

Nguyen

Morokoff

et al. 2018

Translational Oncology

View full text Add to dashboard Cite

The most common primary central nervous system tumor in adults is the glioblastoma multiforme (GBM). The highly invasive nature of GBM cells is a significant factor resulting in the inevitable tumor recurrence and poor patient prognosis. Tumor cells utilize structures known as invadopodia to faciliate their invasive phenotype. In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme. Furthermore, these cellular activities were augmented in cells that survived radiotherapy and temozolomide treatment, indicating that surviving cells may possess a more invasive phenotype posttherapy. We performed a screen of FDA-approved agents not previously used for treating GBM patients with the aim of investigating their “anti-invadopodia” and cytotoxic effects in GBM cell lines and identified a number that reduced cell viability, as well as agents which also reduced invadopodia activity. Importantly, two of these, pacilitaxel and vinorelbine tartrate, reduced radiation/temozolomide-induced invadopodia activity. Our data demonstrate the value of testing previously approved drugs (repurposing) as potential adjuvant agents for the treatment of GBM patients to reduce invadopodia activity, inhibit GBM cell invasion, and potentially improve patient outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs

Whitehead

Nguyen

Morokoff

et al. 2018

Translational Oncology

View full text Add to dashboard Cite

show abstract

“…Second-generation semisynthetic Vinca alkaloids, vinorelbine and vindesine, have shown a broader spectrum of antitumor activity in vitro , along with a decreased neurotoxicity. Vinorelbine was approved as single agent and in combination therapy for the treatment of both hematological and solid tumors, including lung cancer, breast cancer, and gynecological tumors [ 15 ]. Recently, another synthetic Vinca alkaloid, vinflunine, has been approved in Europe for the second-line treatment of metastatic urothelial carcinoma.…”

Section: Microtubule-destabilizing Agentsmentioning

confidence: 99%

Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

Fanale

Bronte

Passiglia

et al. 2015

Analytical Cellular Pathology

View full text Add to dashboard Cite

Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy.

show abstract

“…C is the precursor of the antimetabolite 5-fluorouracil (5-FU), which inhibits the thymidylate synthase enzyme and DNA synthesis, thus preventing cell cycle progression through the S phase [35]. On the other hand, V is a spindle poison that binds β-tubulin and inhibits microtubule polymerization, thus resulting in the activation of the Spindle Assembly Checkpoint (SAC) and in the inhibition of cell cycle progression through the G2/M phase [36,37]. Therefore, C and V have potentially synergistic antitumor activity deriving from their action in two different phases of the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Oral Capecitabine-Vinorelbine Is Associated with Longer Overall Survival When Compared to Single-Agent Capecitabine in Patients with Hormone Receptor-Positive Advanced Breast Cancer

Vernieri

Prisciandaro

Nichetti

et al. 2020

Cancers

View full text Add to dashboard Cite

Background: Single-agent capecitabine (C) is a moderately effective chemotherapeutic compound in the treatment of patients with HER2-negative metastatic breast cancer (mBC). The capecitabine-vinorelbine (CV) combination is also used due to a good tolerability profile, but no studies have demonstrated its superiority over single-agent C. Methods: We conducted a retrospective analysis to compare overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and incidence of adverse events (AEs) in patients with HER2-negative mBC treated with CV vs. single-agent C. Results: Out of 290 patients included in this study, 127 (43.8%) received single-agent C, while 163 (56.2%) patients were treated with CV. Median PFS was similar in patients treated with single-agent C or CV, while CV was associated with significantly longer OS in patients with hormone receptor-positive (HR+) BC. This OS advantage was confirmed at multivariable analysis also after propensity score-based matching of patients according to relevant clinical or tumor characteristics. When compared with single-agent C, CV was associated with higher incidence of G3/G4 and any-grade nausea/vomiting, diarrhea and increased transaminases. Conclusions: While prospective studies are Cancers 2020, 12, 617 2 of 15 needed to confirm our findings, the potential OS advantage of CV over single-agent C in HR+ mBC patients must be weighed against a significantly higher incidence of AEs.

show abstract

True

Cited by 93 publications

References 46 publications

Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs

Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs

Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

Oral Capecitabine-Vinorelbine Is Associated with Longer Overall Survival When Compared to Single-Agent Capecitabine in Patients with Hormone Receptor-Positive Advanced Breast Cancer

Contact Info

Product

Resources

About