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Kamesaki, H

doi:10.1016/s0925-5710(98)00038-3

Cited by 95 publications

(17 citation statements)

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“…Chemotherapy exerts cytotoxic effects mainly via the induction of apoptosis [15,16,17,18,19,20], and there is evidence to suggest that drug-induced programmed cell death contributes greatly to chemotherapy-related neutropenia [21, 22]. Moreover, several functional abnormalities have been reported in neutrophils from cancer patients exposed to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Biological Effects of Pegfilgrastim on Circulating Neutrophils in Breast Cancer Patients Undergoing Dose-Dense Chemotherapy

et al. 2008

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Pegfilgrastim is a covalent conjugate of filgrastim and polyethylene glycol that has proved to be effective in supporting myelopoiesis during chemotherapy. Since very limited information is available on the biological effects of pegfilgrastim on neutrophils exposed to chemotherapy, we analyzed the following parameters in neutrophils of patients undergoing dose-dense chemotherapy for breast cancer: apoptosis, by a TUNEL technique; actin polymerization, using FITC-labeled phalloidin, and alkaline phosphatase activity by cytochemistry. Peripheral blood buffy coat smears were obtained before starting treatment and immediately before each chemotherapy course. After pegfilgrastim stimulation we observed the following: (1) stability of the absolute neutrophil count for the whole duration of treatment and no infectious events; (2) a reduction in the neutrophil constitutive apoptosis rate in comparison with that observed in control patients treated with standard chemotherapy courses with no growth factor support; (3) persistent abnormalities of actin assembly in neutrophils, indicative of changes in cytoskeletal organization, and (4) a significant increase in the activity of leukocyte alkaline phosphatase, a sensitive marker of the later stages of neutrophil maturation. In conclusion, these results suggest that pegfilgrastim improves the neutrophil functions in patients exposed to chemotherapy by inhibition of constitutive apoptosis, thereby prolonging the survival of these cells.

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Section: Introductionmentioning

confidence: 99%

Biological Effects of Pegfilgrastim on Circulating Neutrophils in Breast Cancer Patients Undergoing Dose-Dense Chemotherapy

et al. 2008

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“…Elevation of expression of this antiapoptotic protein appears to contribute to resistance to a variety of antineoplastic agents, both in vitro and in vivo, which include cis-platinum, taxanes, mitoxantrone, Adriamycin, and dexamethasone, in addition to radiation (5)(6)(7)(8)(9)(10). The bcl-2 protein, whereas expressed in very few normal tissues (e.g., B lymphocytes and colon crypt cells), is in contrast, highly expressed in human tumors as diverse as prostate, colorectal, lung, gastric, non-Hodgkin's lymphoma, and in many leukemias (reviewed in Ref.…”

Section: Introductionmentioning

confidence: 99%

Antisense RNA Down-Regulation of bcl-2 Expression in DU145 Prostate Cancer Cells Does Not Diminish the Cytostatic Effects of G3139 (Oblimersen)

Raffo

Lai

Stein

et al. 2004

Clinical Cancer Research

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Purpose: Inhibition of the function of the bcl-2 protein has been postulated to sensitize cells to cytotoxic chemotherapy, and thus provides an attractive target for investigative therapies. G3139, a phosphorothioate antisense oligonucleotide targeted to the initiation codon region of the bcl-2 mRNA, is currently being evaluated in several Phase II and Phase III clinical trials. However, the mechanism of action of this molecule appears to depend on a combination of antisense plus nonantisense events. Indeed, the very idea that bcl-2 is a critical target is, at least in part, an extrapolation from experiments in which intracellular bcl-2 protein concentrations have been dramatically increased, yielding chemoresistant cells.Experimental Design: In this work, we down-regulated the expression of bcl-2 protein by 80 -90% by two different antisense RNA strategies (antisense RNA and small interfering RNA) in DU145 prostate cancer cells.Results: Even after down-regulation of bcl-2 protein expression by either one of these strategies, the cellular phenotype induced by subsequent G3139 treatment (inhibition of cellular growth and the generation of reactive oxygen species) was essentially identical to that induced in mockinfected or wild-type DU145 cells in which bcl-2 protein expression had not been down-regulated previously.Conclusions: These results strongly suggest that bcl-2 expression in DU145 cells is not strongly associated with the prolife phenotype and that the mechanism by which G3139 produces its cytostatic effects in this cell line is bcl-2 independent.

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“…The Bcl-2 protein has been shown to contribute to neoplastic cell expansion by blocking the normal physiological turnover of cells that occurs due to apoptosis (reviewed in Ref.15). Furthermore, overexpression of bcl-2 inhibits apoptosis induced by growth factor withdrawal, radiation damage and multiple types of chemotherapeutic drugs (19)(20)(21)(22)(23)(24). Moreover, recent studies indicate that gene transfer-mediated elevation of Bd-2 protein levels in target cells blocks cellmediated cytotoxicity by the T-cell line and allospecific CTL (25,26).…”

Section: Introductionmentioning

confidence: 99%

BCL-2 Inhibits B7-Induced MHC-Unrestricted Cytolysis Mediated by a Human NK Cell Line

Sun

Teshigawara

Uchida

1996

LIMM

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Recent work demonstrated that B7 expression by tumor cells can enhance antitumor immune responses. However, the B7 molecule is expressed abundantly on most non-Hodgkin's B-cell lymphomas and solid lymphoid tumors. How these tumor cells escape from immune surveillance mechanisms remains unclear. Lately, it has become clear that bcl-2 oncogene is overexpressed in a wide variety of human cancers and renders tumor cells more resistant to cytolytic T-cells (CTL) mediated cytotoxicity. We cloned B7 and B7/Bcl-2 transfectants and compared their susceptibilities to a human natural killer (NK) cell line and normal NK cells. The results demonstrate that Bcl-2 oncoprotein in tumor cells blocks B7-induced cytolysis mediated by a NK cell line and NK cells. Thus, they suggest that Bcl-2 oncoprotein plays a role in tumor avoidance of effective antitumor cytotoxicity.

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Cited by 95 publications

References 0 publications

Biological Effects of Pegfilgrastim on Circulating Neutrophils in Breast Cancer Patients Undergoing Dose-Dense Chemotherapy

Biological Effects of Pegfilgrastim on Circulating Neutrophils in Breast Cancer Patients Undergoing Dose-Dense Chemotherapy

Antisense RNA Down-Regulation of bcl-2 Expression in DU145 Prostate Cancer Cells Does Not Diminish the Cytostatic Effects of G3139 (Oblimersen)

BCL-2 Inhibits B7-Induced MHC-Unrestricted Cytolysis Mediated by a Human NK Cell Line

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