Phase II Study of Taxol in Patients With Untreated Advanced Non-Small-Cell Lung Cancer

Murphy, William K.; Fossella, Frank V.; Winn, Rodger J.; Shin, Dong M.; Hynes, Harry E.; Gross, Howard M.; Davilla, Enrique; Leimert, Joseph T.; Dhingra, Hari M.; Raber, Martin N.; Krakoff, Irwin H.; Hong, Waun Ki

doi:10.1093/jnci/85.5.384

Cited by 397 publications

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“…This is particularly true of therapy with taxanes, such as paclitaxel and docetaxel, which are being used increasingly in patients with metastatic disease secondary to tumors of the breast, prostate, lung, and other sites (1)(2)(3). Such resistance can be primary, resulting in tumors that never respond to a particular drug, or secondary, where tumors respond initially but then become resistant.…”

mentioning

confidence: 99%

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Patel

Chatterjee

Vrbanac

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Paclitaxel has emerged as a front line treatment for aggressive malignancies of the breast, lung, and ovary. Successful therapy of cancer is frequently undermined by the development of paclitaxel resistance. There is a growing need to find other therapeutic targets to facilitate treatment of drug-resistant cancers. Using a proteomics approach, elevated levels of Prohibitin1 (PHB1) and GSTπ were found associated with paclitaxel resistance in discrete subcellular fractions of two drug-resistant sublines relative to their sensitive sublines. Immunofluorescence staining and fractionation studies revealed increased levels of PHB1 on the surface of resistant cell lines. Transiently silencing either PHB1 or GSTπ gene expression using siRNA in the paclitaxel-resistant cancer cell sublines partially sensitized these cells toward paclitaxel. Intriguingly, silencing PHB1 but not GSTπ resulted in activation of the intrinsic apoptosis pathway in response to paclitaxel. Similarly, stably silencing either PHB1 or GSTπ significantly improved paclitaxel sensitivity in A549TR cells both in vitro and in vivo. Our results indicate that PHB1 is a mediator of paclitaxel resistance and that this resistance may depend on the cellular localization of the protein. We suggest PHB1 as a potential target for therapeutic strategies for the treatment of drug-resistant tumors.apoptosis | glutathione-S-transferase Pi | mitochondria | plasma membrane | protein translocation

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mentioning

confidence: 99%

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Patel

Chatterjee

Vrbanac

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Treatment was repeated every 3 weeks. Paclitaxel and cancer of the bladder 607 The dose, infusion rate and schedule of paclitaxel was chosen on the basis of previous phase II and III trials in ovary, breast and lung cancer patients, (Murphy et al, 1993;Eisenhauer et al, 1994;Seidman, 1995). The study was approved by the ethics committees of the three hospitals that took part.…”

Section: Treatmentmentioning

confidence: 99%

Phase II study of paclitaxel in pretreated patients with locally advanced/metastatic cancer of the bladder and ureter

Papamichael

Gallagher²,

Oliver³

et al. 1997

Br J Cancer

115

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Summary Fourteen patients with previously treated, locally advanced/metastatic transitional cell carcinoma (TCC) of the bladder or ureter received paclitaxel at a dose of 200 mg m-2 administered as a 3-h infusion every 21 days. The activity of paclitaxel in this group of patients was modest. The response rates were one partial response (PR) (7%) and three stable disease (SD). There were two early deaths.

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“…Paclitaxel, a member of the taxane class of agents, has been widely used as an antineoplastic agent for >20 years and is effective in the treatment of a number of types of cancer and other malignancies (4)(5)(6). Paclitaxel binds to tubulin and stabilizes microtubule filaments to induce mitotic arrest during the G 2 /M phase and promote apoptosis (7).…”

Section: Introductionmentioning

confidence: 99%

Connexin 43 enhances paclitaxel cytotoxicity in colorectal cancer cell lines

Wang¹,

Zhao²,

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Colorectal cancer has a relatively low sensitivity to paclitaxel. The purpose of this study was to investigate the role of connexin 43 (Cx43), which is a structural component of gap junctional communication (GJC), in paclitaxel cytotoxicity in colorectal cancer cells. Three colorectal cancer cell lines (HCT106, HCT116 and LoVo) were transfected with Cx43 and used to examine paclitaxel cytotoxicity. A western blot assay was used to confirm Cx43 expression in transfected cell lines as well as the expression of several proteins that are associated with paclitaxel cytotoxicity. A parachute dye-coupling assay was used to measure GJC function. An MTT assay was used to analyze the viability of paclitaxel-treated cells. Cx43 expression level and GJC function were significantly upregulated by the transfection (P<0.05). The viability of transfected cells was significantly inhibited compared with that of untransfected cells when treated with paclitaxel (20 or 80 nM) at high culture density but not at low culture density (P<0.05). Cx43 transfection significantly increased the mitotic arrest, tubulin polymerization and apoptosis effects of paclitaxel (P<0.05). It was also found that paclitaxel had an inhibitory effect on GJC function after 12 h of treatment in LoVo cells (P<0.05). These results indicate that Cx43 may serve as a target of paclitaxel chemotherapy for colorectal cancer.

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Phase II Study of Taxol in Patients With Untreated Advanced Non-Small-Cell Lung Cancer

Abstract: A phase II study combining taxol, etoposide, and cisplatin and using hematopoietic stimulating factors is now proposed. The optimal dose for combination chemotherapy has yet to be determined. An important consideration is potential cardiac effects of taxol with other drugs.

Cited by 397 publications

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Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Phase II study of paclitaxel in pretreated patients with locally advanced/metastatic cancer of the bladder and ureter

Connexin 43 enhances paclitaxel cytotoxicity in colorectal cancer cell lines

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