Vinorelbine in Cancer Therapy

Capasso, Anna

doi:10.2174/138945012802009017

Cited by 37 publications

(31 citation statements)

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“…One of the cytotoxics that are commonly used in metastatic breast cancer is vinorelbine [9, 10] particularly because of its good tolerance profile. Vinorelbine is a semisynthetic third generation vinca alkaloid that acts by inhibiting cancer cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Vinorelbine with or without Trastuzumab in Metastatic Breast Cancer: A Retrospective Single Institution Series

2014

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Background. We report our experience with vinorelbine, a widely used chemotherapeutic, in unselected metastatic breast cancer patients treated in clinical routine. Patients and Methods. The data of all patients with metastatic breast cancer receiving vinorelbine with or without trastuzumab during a six year period were reviewed. Patients received vinorelbine intravenous 25–30 mg/m2 or 60–80 mg/m2 orally in days 1 and 8 of a 21 day cycle. Results. Eighty-seven women were included. Sixty-two patients received vinorelbine alone and 25 patients received vinorelbine in combination with trastuzumab. In 67 patients this was the first line treatment for metastatic disease and in 20 patients it was 2nd or later line of treatment. The median TTP was six months (range: 1–45). The median overall survival was 11.5 months (range: 1–83). Seventy patients were evaluable for response. In patients receiving first line treatment 44.4% had a response while in the second and subsequent lines setting 12.5% of patients responded (P = 0.001). Objective response was obtained in 63.6% of patients receiving concomitant trastuzumab and in 25% of patients receiving vinorelbine alone (P = 0.0002). Conclusion. This study confirms a high disease control rate. Response rate and TTP were superior in first line treatment compared to subsequent lines.

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Section: Discussionmentioning

confidence: 99%

Vinorelbine with or without Trastuzumab in Metastatic Breast Cancer: A Retrospective Single Institution Series

2014

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“…For example, eribulin, a non‐taxane synthetic tubulin dynamics inhibitor, binds to a microtubule plus‐end with high affinity, and thereby functions as a suppressor of microtubule dynamics . On the contrary, vinorelbine, another tubulin‐binding drug (TBD), binds to a vinca‐binding domain of a β‐tubulin subunit near the plus‐end of the microtubule and functions as a microtubule destabilizer . It is well‐known that pharmacological effects of TBD are different to each other.…”

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confidence: 99%

Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models

Ito

Hamamichi²,

Abe

et al. 2017

Cancer Science

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We previously reported that eribulin mesylate (eribulin), a tubulin‐binding drug (TBD), could remodel tumor vasculature (i.e. increase tumor vessels and perfusion) in human breast cancer xenograft models. However, the role of this vascular remodeling in antitumor effects is not fully understood. Here, we investigated the effects of eribulin‐induced vascular remodeling on antitumor activities in multiple human cancer xenograft models. Microvessel densities (MVD) were evaluated by immunohistochemistry (CD31 staining), and antitumor effects were examined in 10 human cancer xenograft models. Eribulin significantly increased MVD compared to the controls in six out of 10 models with a correlation between enhanced MVD levels and antitumor effects (R 2 = 0.54). Because of increased MVD, we next used radiolabeled liposomes to examine whether eribulin treatment would result in increased tumoral accumulation levels of these macromolecules and, indeed, we found that eribulin, unlike vinorelbine (another TBD) enhanced them. As eribulin increased accumulation of radiolabeled liposomes, we postulated that this treatment might enhance the antitumor effect of Doxil (a liposomal anticancer agent) and facilitate recruitment of immune cells into the tumor. As expected, eribulin enhanced antitumor activity of Doxil in a post‐erlotinib treatment H1650 (PE‐H1650) xenograft model. Furthermore, infiltrating CD11b‐positive immune cells were significantly increased in multiple eribulin‐treated xenografted tumors, and natural killer (NK) cell depletion reduced the antitumor effects of eribulin. These findings suggest a contribution of the immune cells for antitumor activities of eribulin. Taken together, our results suggest that vascular remodeling induced by eribulin acts as a microenvironment modulator and, consequently, this alteration enhanced the antitumor effects of eribulin.

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“…The growth of cells treated with Dox was found to decline significantly (19). We have also found that MED23 knockdown significantly arrests the mitosis cycle of the breast cancer cells (the number of cells that enter the S stage decrease) (20). The regulatory effect of MED23 on cell cycle may be one of the major mechanisms that regulate its participation in the growth of breast cancer cells.…”

Section: Discussionmentioning

confidence: 93%

MED23 in endocrinotherapy for breast cancer

Lin

Zhang

et al. 2017

Oncol Lett

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We investigated the role of the transcriptional mediator subunit 23 (MED23) in everolimus drug resistance, invasion and metastasis during breast cancer treatment and its molecular mechanism. We also evaluated the endocrinotherapy and prevention method for breast cancer. Breast cancer cell strains were established that can continuously express MED23, as well as inducible MED23-shRNA expression plasmids. The inductive agent, doxycycline (Dox), was added to the water for long-term silencing of MED23 in intratumoral cells. We conducted experiments on the role of MED23 in the regulation of invasion and metastasis of breast cancer using cell culture, western blotting, MTT proliferation experiment, fluorescent quantitative PCR and chromatin immunoprecipitation (ChIP). The silencing of MED23 significantly inhibited cellular growth and proliferation as well as soft agar cloning. Silencing of MED23 strengthened the sensitivity of the everolimus-resistant breast cancer cell strains BT474 and MCF-7/ADM cells to everolimus medication. The silencing of MED23, in combination with everolimus, inhibits the cell cycle progress of breast cancer cells. ChIP indicated that the mutual regulation of HER2 and MED23 also participates in the formation of the everolimus drug resistance mechanism. Therefore, MED23 plays an important role in everolimus drug resistance, invasion, and metastasis of breast cancer. As a potential molecular therapeutic target of breast cancer, MED23 overcomes drug resistance in clinical endocrinotherapy and controls the distal relapse and metastasis in breast cancer by the targeted silencing of MED23.

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Vinorelbine in Cancer Therapy

Cited by 37 publications

References 0 publications

Vinorelbine with or without Trastuzumab in Metastatic Breast Cancer: A Retrospective Single Institution Series

Vinorelbine with or without Trastuzumab in Metastatic Breast Cancer: A Retrospective Single Institution Series

Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models

MED23 in endocrinotherapy for breast cancer

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