As an antitumor agent, interleukin-12 (IL-12) has been revealed to be a key regulator of the immune response, particularly that involving CTL and natural killer (NK) cells. We report herein the ...antiangiogenesis effect of IL-12 on human as well as murine tumors in NK-depleted severe-combined immunodeficient mice using fibroblasts genetically engineered to secrete this cytokine. Although the in vitro growth of tumor cells was not affected by the presence of IL-12, coinoculation of IL-12-secreting fibroblasts strongly inhibited tumor growth in immunodeficient mice. The neovascularization surrounding the tumor was remarkably inhibited in the area in which the IL-12-secreting fibroblasts were implanted, resulting in the suppression of tumor growth. Lectin staining in tumor sample sections also showed a significant reduction in the number of vessels. The RNA expression of IFN-gamma and its inducible antiangiogenic chemokine IFN gamma-inducible protein 10 was stimulated in endothelial cells cultured with IL-12. It was also found that IL-12 down-regulated the expression of the endothelial cell mitogens vascular endothelial growth factor and basic fibroblast growth factor. The antitumor effects of IL-12 were accompanied by interesting histological changes consisting of a high degree of keratinization and apoptosis and a decrease in the proliferation rate of human tumors and extensive necrosis in the murine ones.
Proteome analysis of prostate cancer Kuruma, H; Egawa, S; Oh-Ishi, M ...
Prostate cancer and prostatic diseases,
03/2005, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In this paper, we briefly review cancer proteomics in general, with particular attention to our proteome analyses of prostate cancer. Our efforts include development of new tools and novel approaches ...to discovering proteins potentially useful as cancer diagnostic and/or prognostic biomarkers or as therapeutic targets. To this end, we analyzed prostate cancer proteomes using two-dimensional gel electrophoresis employing agarose gels for the initial isoelectric focusing step (agarose 2-DE), with mass spectrometry used for protein identification. Agarose 2-DE offers advantages over the more widely used immobilized pH gradient 2-DE for separating high molecular mass proteins (15-500 kDa), thereby increasing its power to detect changes in the cancer's high-molecular mass proteomes.
Dipeptidyl peptidase IV (DPP IV) in normal human serum was purified 14, 400-fold with a 25% yield to homogeneity. The molecular weight of the purified enzyme was approximately 110, 000 on SDS-PAGE, ...almost the same as that of human kidney membrane-bound DPP IV. No difference was found between the two enzymes enzymologically and immunologically, either in substrate specificity, susceptibility to inhibitors, or cross-reactivity with an antirat kidney DPP IV antibody, or in their ability to bind adenosine deaminase. However, the N-terminal amino acid sequence of serum DPP IV lacked the transmembrane domain of the membrane-bound enzyme and started at the 39th position, serine, from the N-terminus predicted from the cDNA nucleotide sequence. These results suggest that membrane-bound DPP IV loses its transmembrane domain upon release into the serum, and that its structure on the plasma membrane is not required for its binding to adenosine deaminase.
The use of prostate-specific antigen (PSA) for early detection of prostate cancer has dramatically increased the reported incidence of this malignancy but its net benefit is unclear and remains ...controversial at present. Although several countries have adopted prostate cancer screening as a health policy, a reduction of cancer mortality would be an ultimate indication of the effectiveness of early detection. Since screening upon patient request cannot be refused, appropriate information should be provided until further support is available.
Objectives To assess the time trends, morbidity and mortality of contemporary anatomical radical retropubic prostatectomy (RRP) in a multi‐institutional study in Japan, where RRP has become more ...popular in the last decade.
Patients and methods Between January 1991 and August 1998, 638 patients underwent RRP at seven urological centres in Japan. Major complications (within 30 days of surgery) and the 30‐day mortality were reviewed retrospectively. Of the patients, 12.9% were < 60 years old, 56.3% were 60–69 years old and 30.9% were 70 years old (median age 67).
Results The number of RRPs increased markedly, by more than sevenfold, from 1991–92 to 1996–97, mainly because there were more patients undergoing RRP in their sixth decade. The contribution of T1c disease increased in absolute and relative terms, from 13.9% in 1991–92 to 37.9% in 1997–98. Over time, the mean blood loss and the allogeneic transfusion rate decreased steadily. There was a trend toward more favourable outcomes for pathological variables (an increased percentage of organ‐confined disease, decreased margin positivity and a decreased incidence of positive lymph node metastasis). The most common complications were wound‐related (7.5%), or anastomotic leakage (4.1%). Major cardiopulmonary complications occurred in only two patients (0.31%, both pulmonary embolisms). One patient died from cerebral haemorrhage within 30 days of surgery, giving a mortality rate of 0.16%.
Conclusions This study indicates a trend towards selecting patients most likely to benefit from RRP. Although the procedure is technically demanding, it can have an acceptably low rate of early complications, little mortality and need for allogeneic transfusion. The assessment of morbidity suggests a lower incidence of catastrophic thrombo‐embolic and cardiac complications in Japanese patients than in Western men. The present data may be useful in decision‐analysis models evaluating the role of therapy for Asian men with early‐stage prostate cancer.
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