Cancer research
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Energy restriction reduces prostate tumor growth in transplantable tumor models in rodents, which suggests that excessive energy intake may contribute to the risk of prostate cancer. The association of total energy intake across the normal range with prostate cancer has not been consistent in epidemiological studies. We prospectively evaluated the joint associations of energy intake and body size or physical activity with prostate cancer. ⋯ Also, the association of energy intake with metastatic and fatal prostate cancer was restricted to men who were younger [in stratum
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Failure to control localized prostate cancer can result not only in localized disease progression but also distant metastatic spread. Whereas significant advances in both surgical technique and radiation therapy have improved local control rates with decreased morbidity, consistent long-term control remains elusive. This study investigates the potential of 17-N-allylamino-17-demethoxy geldanamycin (17AAG), a geldanamycin derivative, to sensitize tumor cells to ionizing radiation, permitting a significant improvement to targeted radiotherapies of prostate carcinoma. ⋯ Terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and Ki67 staining of spheroid sections revealed the increased growth control to be a function of spheroids failing to re-enter the cell cycle. For all 6 Gy experiments, cells remaining from each of the spheroids that failed to regrow were transferred to adherent dishes to evaluate clonogenicity; growth-controlled spheroids also failed to form colonies within 2 weeks of being plated. These results suggest that significant gains in treatment effectiveness may be obtained by combining these treatment modalities, warranting additional preclinical investigation.
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LEC/chTNT-3, a chemokine fusion protein generated previously in our laboratory, produces a 40-60% reduction in well-established solid tumors of the BALB/c mouse. In this study, CD25(+) T-cell depletion was used in combination with LEC/chTNT-3 treatment to enhance the therapeutic value of this approach. In two tumor models (Colon 26 and RENCA), this combination immunotherapy produced complete regression of established s.c. tumors after 5 consecutive days of i.v. treatment. ⋯ Other studies using real-time PCR, ex vivo proliferation, and intracellular cytokine staining with lymphocytes from tumor draining lymph nodes, suggested that this combination treatment was associated with increased T-helper 1 cytokine expression, enhanced T-cell activation, and increased IFN-gamma production by T cells. Rechallenge experiments showed that combination LEC/chTNT-3 treatment and CD25(+) depletion produced long-acting memory cells capable of preventing re-engraftment of the same but not different tumor cell lines. These studies suggest that LEC/monoclonal antibody fusion proteins, when used in combination with CD25(+) T-cell depletion, is a viable method of immunotherapy for the treatment of solid tumors.