Chemo-endocrine therapy in patients with stage D2 prostate cancer

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.     

A composite nasolabial flap for an entire ala reconstruction.

BACKGROUND: It is difficult to reconstruct an entire alar defect. We report a case of an entire alar reconstruction carried out in two stages with a composite nasolabial flap lined with retroauricular skin and supported with the attached conchal cartilage. OBJECTIVE: A composite nasolabial flap was applied for reconstruction of entire alar defect in this patient. METHODS: The lining skin for the flap was obtained from retroauricular region acceptable to the patient, and the conchal cartilage was used simultaneously for support and as the attachment for the lining skin. The flap was then replaced and secured. Half a year later, the flap was flipped and transferred to the alar defect as a second step. RESULTS: The final shape and texture were satisfactory. All procedures were performed under local anesthesia. CONCLUSION: Our design of composite flap has been successfully utilized to repair an entire alar defect with cosmetically and functionally good results, minimizing the donor area and the resulting operation scars. This composite nasolabial flap is thought to be the best choice of a flap for an entire alar defect reconstruction.     

Glutathione redox regulates lipopolysaccharide-induced IL-12 production through p38 mitogen-activated protein kinase activation in human monocytes: role of glutathione redox in IFN-gamma priming of IL-12 production

We examined whether changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione of human monocytes regulate lipopolysaccharide (LPS)-induced IL-12 production and defined the molecular mechanism that underlies glutathione redox regulation. Monocytes exposed to glutathione reduced form ethyl ester (GSH-OEt) or maleic acid diethyl ester (DEM) increased or decreased the intracellular GSH/GSSG ratio, respectively. LPS-induced IL-12 production and p38 mitogen-activated protein (MAP) kinase activation were enhanced by GSH-OEt but suppressed by DEM. Selective p38 inhibitors showed that p38 promoted GSH-OEt-enhanced IL-12 production. Furthermore, IFN-gamma priming increased the GSH/GSSG ratio and enhanced IL-12 production through p38, and DEM negated the priming effect of IFN-gamma on p38 activation and IL-12 production as well as on the GSH/GSSG ratio. These findings reveal that glutathione redox regulates LPS-induced IL-12 production from monocytes through p38 MAP kinase activation and that the priming effect of IFN-gamma on IL-12 production is partly a result of the glutathione redox balance.     

Susceptibility of thyroid cancer cells to 7-hydroxystaurosporine-induced apoptosis correlates with Bcl-2 protein level.

7-Hydroxystaurosporine (UCN-01) is a selective protein kinase C (PKC) inhibitor and is being developed as a novel anticancer agent. Because of reports that PKC may be involved in the pathogenesis of some forms of thyroid cancers, we examined four thyroid carcinoma lines (FRO, KAT5, NPA, and WRO). These cells were found to have different susceptibility to UCN-01 treatment, and there appeared to be a correlation between UCN-01-induced death and expression levels of endogenous Bcl-2. KAT5 cells, which normally express a low amount of Bcl-2, exhibited significantly higher sensitivity to UCN-01-induced death than the other cell lines. Of interest, susceptibility did not relate to PKC activity or its inhibition by UCN-01. In order to investigate the role of Bcl-2 in UCN-01-induced death, KAT5 cells were transfected to overexpress Bcl-2. KAT5/Bcl-2 cells were capable of conferring resistance to UCN-01-induced death. Furthermore, upregulating of Bcl-2 by 1alpha,25-dihydroxyvitamin D3 (VD3) could protect primary thyroid cell from death induced by UCN-01. Both in situ TUNEL staining and the flow cytometric analysis of cytokeratin-18 (CK18) cleavage confirmed that UCN-01 was indeed inducing apoptosis, and that this effect was inhibited by increased expression of Bcl-2. These results suggest that the Bcl-2 can block the UCN-01-activated cell death pathway and that the expression of Bcl-2 is inversely related to thyroid carcinoma cell susceptibility to UCN-01. Therefore, the analysis of the expression of apoptosis suppressors provides a basis for the use of UCN-01 in the treatment of thyroid cancer.     

Identification of Cha o 3 homolog Cry j 4 from Cryptomeria japonica (Japanese cedar) pollen: Limitation of the present Japanese cedar–specific ASIT

Background

About one-third of the Japanese population suffers from Japanese cedar pollinosis, which is frequently accompanied by Japanese cypress pollinosis. Recently, a novel major Japanese cypress pollen allergen, Cha o 3, was discovered. However, whether a Cha o 3 homolog is present in Japanese cedar pollen remains to be determined.

Ambroxol inhibits platelet-derived growth factor production in human monocytic cells

Several growth factors, including platelet-derived growth factor (PDGF), have been implicated in the mechanism of lung and airway remodeling. We investigated the effect of ambroxol, trans-4-[(2-amino-3,5-dibromobenzyl) amino] cyclohexanol hydrochloride, on the lipopolysaccharide-induced PDGF production in human monocytic cells, THP-1. Ambroxol inhibited the lipopolysaccharide-induced PDGF-AB production via PDGF-A mRNA expression. Lipopolysaccharide activated p44/42 extracellular signal-regulated kinase (ERK), and ambroxol attenuated the lipopolysaccharide-induced p44/42 ERK activation. Furthermore, mitogen-activated protein kinase kinase (MEK)-1-specific inhibitor, 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD 98059), blocked the lipopolysaccharide-induced p44/42 ERK activation and PDGF production. These findings indicate that ambroxol inhibits the lipopolysaccharide-induced PDGF production due to the suppression of p44/42 ERK activity.     

Effect of flavonoids on cell cycle progression in prostate cancer cells.

The effect of some flavonoids, which are components of fruits, vegetables, and peas, on the cell cycle progression of human LNCaP prostate cancer cells has been investigated in this study. Genistein arrested the cell cycle at the G2/M phases, which is attributed to the suppression of cyclin B expression. In addition, genistein induced the cyclin-dependent kinase inhibitor p21, which does not depend on p53 activation. Apigenin and luteolin also increased p21 levels, but quercetin did not. Apigenin induced p21 production through a p53-dependent pathway, but luteolin did so in a p53-independent manner. These results suggest that flavonoids are potent regulators of cyclin B and p21 for cell cycle progression, which may play some roles in prevention of carcinogenesis.     

Induction of human monocyte-mediated tumor cell killing by alpha or beta interferon

Human blood monocytes, separated on a continuous percoll gradient, were not cytotoxic to allogeneic A375 melanoma cells. The monocyte monolayers were activated to become tumoricidal by incubation for 24 hr with interferon (IFN)-alpha or beta at concentrations of more than 1,000 IU/ml. Significant and reproducible activation of the monocytes was achieved by incubating them with 10,000 IU/ml of IFN-alpha or IFN-beta for 24 hr. Similarly, suspended, but not plated, monocytes were activated to a tumoricidal state by interaction with IFN-alpha or IFN-beta. Monocytes that had lost tumoricidal activity during culture, were reactivated by a second exposure to IFN-alpha. Fluorescence analysis showed that the monocyte-rich adherent monolayers were contaminated with up 2.0% of natural killer (NK) cells. Pretreatment of isolated monocyte preparations with anti-NK cell monoclonal antibody (Leu-11b) to deplete them of NK cell activity did not inhibit the monocyte-mediated cytotoxicity. These results indicate that human monocytes are rendered tumoricidal by direct interaction with IFN-alpha or IFN-beta, although more than 1,000 IU/ml of IFN-alpha or IFN-beta is required for maximal expression of monocyte activation.     

A review of epidemiological studies about pulse wave velocity for prevention of cardiovascular disease

Early arteriosclerosis can be prevented by medication and life style changes. However, late cardiac disease, called cardiovascular disease, could be fatal or have severe sequelae. Therefore, it is important to develop a method for early diagnosis. Since no symptoms become evident until endothelial/vascular dysfunction, a simple and sensitive diagnostic method using a biological parameter needs to be developed for prevention and medical treatment. Pulse wave velocity (PWV) is a noninvasive and simple measure for evaluating arterial wall stiffness and several studies have indicated this is a good marker for vascular damage, although not all results were consistent. This review concerns the following three aspects: 1. PWV as a marker of vascular damage 2. PWV as a prognostic predictor 3. Brachial-ankle PWV (baPWV) Blood pressure is strongly related with PWV, along with BMI, fasting blood glucose, and cholesterol. However, no relation was rated cigarette smoking. While many reports have shown that rise of PWV can serve as a prognostic predictor of disease, the situation with baPWV remains unclear. It is to be expected that improvements in methods for PWV will greatly contribute to primary and secondary prevention in the future.