Breast cancer enhancement

Zhang DH, Tai LK, Wong LL, Sethi SK, Koay ES. Proteomics of breast cancer Enhanced expression of cytokeratinl9 in human epidermal growth factor receptor type 2 positive breast tumors. Proteomics 2005 5(7) 1797-1805. 

Pinl Murine breast cancer Enhances cyclin D1 transcription and stabilization 79... 

Whereas epidermal growth factor (EGF) enhances the radiosensitivity of human squamous ceU carcinoma cells in vitro (197), addition of EGF to hormone-deprived MCE-7 breast cancer cells prior to irradiation results ia iacreased radioresistance (198). An anti-EGE-receptor monoclonal antibody blocks the abiUty of EGE to enhance growth and radioresistance. Tumor cells, the growth of which is stimulated by EGE, appear to be protected those where growth is iohibited are sensitized (198). 

McKallip RJ, Nagarkatti M, Nagarkatti PS. Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J Immunol 2005 174 3281-9. 

Thus, oxygen radical production by leukocytes can be responsible for cancer development. However, the levels of leukocyte oxygen radical generation depend on the type of cancer. For example, PMNs and monocytes from peripheral blood of patients with lung cancer produced a diminished amount of superoxide [169], Timoshenko et al. [170] observed the reduction of superoxide production in bronchial carcinoma patients after the incubation of neutrophils with concanavalin A or human lectin, while neutrophils from breast cancer patients exhibited no change in their activity. Chemotherapy of lung and colorectal carcinoma patients also reduced neutrophil superoxide production. Human ALL and AML cells produced, as a rule, the diminished amounts of superoxide in response to PMA or FMLP [171], On the other hand total SOD activity was enhanced in AML cells but diminished in ALL cells, while MnSOD in AML cells was very low. It has been proposed that decreased superoxide production may be responsible for susceptibility to infections in cancer patients. 

It has been suggested that tamoxifen, one of the most effective therapeutic and chemopreventive agent for breast cancer, modulates protein kinase C through oxidative stress in breast cancer cells [194], Unfortunately, most breast cancers initially responsive to tamoxifen treatment later become resistant. Schiff et al. [195] suggested that the conversion of breast tumors to a tamoxifen-resistant phenotype is associated with oxidative stress and depends on significantly enhanced SOD activity in tumors. 

Baselge, ]., et al., "Recombinant Humanized Anti-HER2 Antibody (HERCEPTIN) Enhances the Antitumor Activity of Paclitaxel and Doxorubicin Against HER2/neu Overexpressing Human Breast Cancer Xenografts," Cancer Res., 58, 2825-2831 (1998). 

Metastatic bone disease (MBD) is characterized by very high levels of bone turnover in regions proximal to the tumour [33]. Bone resorption inhibitors such as bisphosphonates represent the current standard of care for the treatment of bone metastases primarily due to breast or prostate cancer and multiple myeloma. It has been proposed that other strong anti-resorptives such as a Cat K inhibitor could be useful in the treatment of bone metastases. Evidence for this has been presented in the form of a preclinical MBD model in which human breast cancer cells are implanted into nude mice. Treatment with a Cat K inhibitor gave a significantly lower area of breast cancer-mediated osteolytic lesions in the tibia [34]. In a separate study, the efficacy of a Cat K inhibitor in the reduction in tumour-induced osteolysis was found to be enhanced in the presence of the bisphosphonate zolendronic acid [35,36]. When prostate cancer cells were injected into the tibia of SCID mice, treatment with a Cat K inhibitor both prevented and diminished the progression of cancer growth in bone [37]. 

Inverse Relationship between Protease Inhibitors and Metastatic Ability. All proteases, apart from possibly CD, appear to be controlled by endogenous inhibitors. In theory, therefore, the ability of malignant cells to produce metastasis could depend not only on the levels of the specific protease, but also on the concentration of relevant endogenous inhibitors. Thus, the presence of high levels of protease inhibitors might inhibit metastasis, while low levels of inhibitors might enhance metastasis. An inverse relationship between a number of specific inhibitors and metastatic potential has now been shown. Some examples of this type of relationship include TIMP-1 in Swiss 3T3 cells (K4), cysteine protease inhibitors in mouse melanoma cells (R6), and an alpha-1-proteinase inhibitor in rat mammary carcinomas (N2). Furthermore, a newly described serine protease inhibitor, known as maspin, was found to be expressed less frequently in advanced human breast cancers compared with early cancers (Z2). 

The molecular interactions between PTEN and FAK were studied in glioblastoma and breast cancer cells lacking PTEN. The PTEN trapping mutant bound wild-type FAK, requiring FAK autophosphorylation site Tyr397. In PTEN-mutated cancer cells, FAK phosphorylation was retained even in suspension after detachment from extracellular matrix, accompanied by enhanced PI3-K association with FAK and sustained PI3-K activity. PTEN-mutated cells were resistant to apoptosis in suspension, but most of the cells entered apoptosis after expression of exogenous PTEN or... 

On June 2, 2004, the PDA gave an approvable letter to market efaproxaril if the ongoing phase-three trial, called ENRICH (Enhancing Whole Brain Radiation Therapy in Patients with Breast Cancer and Hypoxic Brain Metastases), designed specifically for the use of efaproxaril to treat metastatic breast cancer to brain, is successful. The ENRICH phase three trial will seek to enroll approximately 360 patients at up to 50 cancer centers across North/South America and Europe. In the letter, the PDA stated, if the study shows effectiveness in this population (increased survival) using the prespecified analysis, and the study is otherwise satisfactory, we believe it would, together with the subset result in RT-009, support approval (http //biz.yahoo.eom/prnews/040602/law025 l.html). 

SMYD2 (KMT3C) SMYD3 Suppressor of p53 transcriptional activity [34] Overexpression and enhanced breast cancer cell growth [93] Overexpression also in colorectal and hepatocellular carcinoma [94] H3K56, p53K370... 

Hamamoto, R., Silva, F.P., Tsuge, M., Nishidate, T, Katagiri, T, Nakamura, Y. and Furukawa, Y. (2006) Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Science, 97, 113-118. 

Ferry DR, Smith A, Malkhandi J, F e DW, deTakats PG, Anderson D, Baker J, Kerr DJ (1996) Phase 1 clinical trial of the flavonoid quercetin pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res 2 659-668 Findik D, Song Q, Hidaka H, Lavin M (1995) Protein kinase A inhibitors enhance radiation-induced apoptosis. J Cell Biochem 57 12-21 Fine RL, Patel J, Chabner BA (1988) Phorbol esters induce multidrug resistance in human breast cancer cells. Proc Natl Acad Sci USA, 85 582-586 Finkenzeller G, Marme D, Hug H (1992) Inducible overexpression of human protein kinase C in NIH 3T3 fibroblasts results in growth abnormalities. Cell Signall 4 163-177... 

Scaglione-Sewell B, Abraham C, Bissonnette M, Skarosi SF, Hart J, Davidson NO, Wali RK, Davis BH, Sitrin M, Brasitus TA (1998) Decreased FKC alpha expression increases cellular proliferation, decreases differentiation, and enhances the transformed phenotype of CaCo-2 cells. Cancer Res 58 1074-1081 Scala S, Dickstein B, Regis J, Szallasi Z, Blumberg PM, Bates SE (1995) Bryostatin 1 affects P-glycoprotein phosphorylation but not function in multidrug-resistant human breast cancer cells. Clinical Cancer Res 1 15851-1587 Scanlon, KJ, Kashani-Sabet M, Tone T, Funato T (1991) Cisplatin resistance in human acancers. Pharmac Ther 52 385-406... 

Pietras RJ, Poen JC, Gallardo D, WongvipatPN, Lee HJ, Slamon DJ. Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 1999 59(6) 1347-1355. 

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