Chemotherapy-induced apoptosis

Liu JR, Fletcher B, Page C, Hu C, Nunez G, Baker V. Bcl-xL is expressed in ovarian carcinoma and modulates chemotherapy-induced apoptosis. Gynecol Oncol 1998 70(3) 398-403. 

The Bcl-2 family has been extensively investigated and has become the target of many approaches to modulate its expression and function. Bcl-2 antisense oligonucleotides are able to induce apoptosis in leukemia cell line and primary cells, and enhance chemotherapy-induced apoptosis (K4). This approach has already been implemented successfully in a phase I study in treating lymphoma patients (W7). 

Quinn JE, Kennedy RD, Mullan PB et al. BRCAl functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res 2003 63 6221-6228. 

Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. 2002. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 62 3868-3875. 

Kaufmann, S.H., Desnoyers, S., Ottaviano, Y., Davidson, N.E. and Poirier, G.G. (1991) Specific proteolytic cleavage of poly (ADP-ribose) polymerase an early marker of chemotherapy-induced apoptosis. Cancer Res., 53, 3976-3985. 

Ambrosini G, Sambol EB, Carvajal D et al (2007) Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1. Oncogene 26 3473-3481... 

Down-regulation of SIP biosynthesis provides another therapeutic modality for the treatment of cancers. On the other hand, exogenous SIP treatment exerts a protective role against cell death in normal (non-cancerous) human cells (Tilly and Kolesnick, 2002). Additionally, SIP has suppressive effects against chemotherapy-induced apoptosis in the ovary (Tilly and Kolesnick, 2002), and also blocked male germ cell apoptosis in the human testis (Suomalainen et al.,... 

As mentioned above, experimental dietary supplementation of curcumin was accompanied by a decrease in the activation of apoptosis by cyclophosphamide, as well as a decrease in JNK activation. These results demonstrate that curcumin can inhibit chemotherapy-induced apoptosis by inhibiting ROS generation and blocking JNK function, effects which would be counterproductive for breast cancer patients undergoing chemotherapy [131]. 

Kaufinann SH, Desnoyers S, Ottaviano Y et al. Specific proteolytic cleav e of poly(ADP-tibose) polymerase An early marker of chemotherapy-induced apoptosis. Cancer Res 1993 53(17) 3976-3985. 

Figure 13.5 Difference in patient outcome in cancer patients showing an increased uptake of [ "TcJBTAP annexin V (Apomate ), indicating a positive response to chemotherapy-induced apoptosis, vs. those demonstrating a low uptake of the radiotracer. This data is reproduced with permission from Ref. (12).

Jones D, Broad R, Madrid L, Baldwin AJ, Mayo M. Inhibition of NF-kappaB sensitizes non-small eell lung eaneer eells to chemotherapy-induced apoptosis. Ann Thorac Surg 2000 70 930-936. 

Kobayashi D, Watanabe N, Yamauchi N, Tsuji N, Sato T, Sasaki H, Okamoto T, Niitsu Y (1997) Protein kinase C inhibitors augment tumor-necrosis-factor-induced apoptosis in normal human diploid cells. Chemotherapy 43 415-423... 

Of course other methods of radiation enhancement may take place with reoxygenation of hypoxic tumor cells that may be increased with the use of chemotherapies like paclitaxel or gemcitabine (41,42), improved drug access to the tumor cells after radiotherapy, or a lowering of the threshold for radiation-induced apoptosis as has been described with the use of gemcitabine (43). 

Apoptosis had been acknowledged as a distinct pathological mechanism in tumor responding to anticancer therapies [29]. It was further noted that the main purpose of anticancer chemotherapy was to kill the tumor cells by inducing apoptosis and triggering the specific apoptotic pathway, rather than by affecting cellular metabolism. Phenothiazines in combination therapy with caffeine were reported to be potent to cure cancer. 

Not only is calcitriol an important determinant for the differentiation of osteo-clastprecursor cells, it also directs the differentiation and maturation of normal and leukemic cells into monocytes, and potentiates apoptosis induced by 9-cis-retinoic acid, although it does not induce apoptosis itself. This suggests the possibility of what has been called maturation therapy for leukemia rather than conventional chemotherapy (James et al., 1999). 

Recombinant human/mouse MoAB that binds to the EGFR and inhibits the binding of EGFR and other growth factors EGFR is overexpressed in some solid tumors such as colorectal cancer cetuximab inhibits cell cycle progression induces apoptosis may enhance the effects of some chemotherapy agents and radiation... 

Triptolide has been shown to induce apoptosis of several human cancer cell lines grown in culture and to inhibit tumor development in a murine breast cancer model " but has shown toxicity at high doses. The 14-succinyl sodium salt of triptolide (34), known as PG490-88, suppresses tumor growth without toxicity and has entered Phase I clinical trials the data is summarized as follows Our results suggest a potential role of PG490-88 alone and in combination with chemotherapy as a novel antineoplastic regimen for the treatment of patients with solid tumors. ... 

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