ABSTRACT
Colletoic acid, a novel 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor, was found and isolated from the cultured broth of the producing fungus Colletotrichum gloeosporioides SANK 21404. Its structure was determined to be a novel acorene-type sesquiterpene by several spectroscopic methods. The absolute structure of colletoic acid was established using a modified Mosher's method and single-crystal X-ray diffraction analysis.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors , Colletotrichum/chemistry , Cyclopentanes/pharmacology , Enzyme Inhibitors/pharmacology , Spiro Compounds/pharmacology , 11-beta-Hydroxysteroid Dehydrogenase Type 2/antagonists & inhibitors , Chemical Phenomena , Chemistry, Physical , Colletotrichum/classification , Crystallography, X-Ray , Cyclopentanes/chemistry , Dose-Response Relationship, Drug , Esters/chemical synthesis , Fermentation , Humans , Kinetics , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Sesquiterpenes , Spiro Compounds/chemistryABSTRACT
A case of monotypic variant of epithelioid angiomyolipoma (AML) observed in a 62-year old woman is reported. The patient complained of abdominal fullness caused by a huge left renal mass without evidence of tuberous sclerosis complex. Imaging studies showed a left renal mass with an area showing hemorrhage and necrosis. The left renal mass, spleen and pancreatic tail were removed en bloc transabdominally. The resected tumor weighed 1200 g and showed focal necrosis and hemorrhage. Microscopically, the tumor was composed exclusively of atypical polygonal cells with copious eosinophilic cytoplasm, pleomorphic nuclei and prominent nucleoli. Tumor cells were considered to derive from perivascular epithelioid cells, and exhibited strong positive staining for HMB-45 and c-KIT, but were negative for epithelial, smooth muscle, and neural markers. As this tumor had none of the typical elements of classic AML, the final pathological diagnosis was monotypic epithelioid AML.
Subject(s)
Angiomyolipoma/pathology , Kidney Neoplasms/pathology , Neoplasms, Glandular and Epithelial/pathology , Aged , Angiomyolipoma/metabolism , Antigens, Neoplasm , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Kidney Neoplasms/metabolism , Melanoma-Specific Antigens , Necrosis , Neoplasm Proteins/metabolism , Neoplasms, Glandular and Epithelial/metabolism , Proto-Oncogene Proteins c-kit/metabolismABSTRACT
Two cases of pheochromocytoma incidentally discovered in long-term hemodialysis patients are reported. Case 1 was a 47-year-old-man who had been receiving hemodialysis for 18 years. Case 2 was a 33-year-old woman who had been receiving hemodialysis for 12 years. Both cases were normotensive, and no specific symptoms suggesting pheochromocytoma were seen. Plasma norepinephrine (NE) levels were not elevated in both cases; however, the level of epinephrine (E) was double the normal range in Case 2. After surgery, plasma E level returned to the normal range in Case 2; however, the level of NE remained almost the same as the preoperative value in both cases. Plasma catecolamine levels in long-term hemodialysis patients with pheochromocytoma are reviewed in the present report, and the efficacy of imaging methods in the diagnosis of pheochromocytoma are discussed.
Subject(s)
Adrenal Gland Neoplasms/diagnosis , Pheochromocytoma/diagnosis , Renal Dialysis , Adult , Humans , Incidental Findings , Male , Middle Aged , Time FactorsABSTRACT
BACKGROUND: Radical retropubic prostatectomy (RRP) has resulted in substantial blood loss and the frequent need for homologous blood transfusion. In this study, the efficacy of autologous blood transfusion, from medical and financial perspectives, was evaluated in patients undergoing RRP. METHODS: Between 1994 and 2000, 80 patients with localized prostate cancer underwent RRP in our institute. Based on informed consent, preoperative donation of autologous blood (PDA) was performed in 65 out of 80 patienets. Four or six units were donated during the first 3 years; however, donation units were reduced to a maximum of 4 units since 1997 onwards. The discard rate of donated blood and frequency of homologous transfusion were examined. Changes of hematocrit (Ht) and hemoglobin (Hb) levels through donation and surgery and important factors that may affect postoperative levels of Ht and Hb were evaluated in 56 patients receiving 4-unit donations. RESULTS: Overall, 2 or 4 units of donated blood were discarded in four patients and homologous transfusion was required in two patients. In 56 patients receiving 4-unit donation, the mean Ht level at predonation was 43.3%. Following donation, this decreased to 35.7%. The administration of recombinant human erythropoietin (rHuEpo) relieved declining Ht levels following donation, but changes in Ht levels after surgery were minor. Important factors related to postoperative decline of Ht and Hb levels were operative time and blood loss. CONCLUSIONS: The program of 4-unit PDA can be performed safely without rHuEpo injection, and it is useful to reduce the risk of requiring homologous transfusion. However, more efficient programs to relieve patient burden and to reduce medical cost are needed.
Subject(s)
Blood Transfusion, Autologous , Erythropoietin/administration & dosage , Prostatectomy/methods , Prostatic Neoplasms/surgery , Aged , Blood Loss, Surgical , Hematocrit , Hemoglobins/metabolism , Humans , Male , Middle Aged , Prostatic Neoplasms/blood , Recombinant ProteinsABSTRACT
Since hypoxia has been considered to enhance metastatic potential in solid tumors via a neo-angiogenesis caused by vascular endothelial cell growth factors (VEGFs) induced by hypoxia inducible factor-1alpha (HIF-1alpha), the effects of hypoxia on human seminoma cell lines were examined in terms of growth, morphology, gene expression, protein expression and cell cycle perturbation. Growth was inhibited in long-term cultures with morphological changes to the spindle form. The gene expression of VEGF-C was markedly enhanced and the production of VEGF-A increased during hypoxia, although HIF-1alpha was not upregulated at the protein or message level. Hypoxic culture caused G1 cell cycle arrest with upregulation of the p15/ink4b and p27/Kip1 genes, whereas no increase of apoptotic cells was observed on up-regulation of the heat shock protein (HSP) 70 gene. The adhesion molecules were only slightly altered.
Subject(s)
Hypoxia , Seminoma/metabolism , Testicular Neoplasms/metabolism , Up-Regulation , Apoptosis , Cell Adhesion , Cell Cycle Proteins/metabolism , Cell Division , Cyclin-Dependent Kinase Inhibitor p15 , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Cyclin-Dependent Kinase Inhibitor p27 , DNA, Complementary/metabolism , Endothelial Growth Factors/biosynthesis , Flow Cytometry , G1 Phase , HSP70 Heat-Shock Proteins/metabolism , Humans , Hyaluronan Receptors/biosynthesis , Immunohistochemistry , Intercellular Adhesion Molecule-1/biosynthesis , Lymphatic Metastasis , Male , RNA/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Seminoma/pathology , Testicular Neoplasms/pathology , Time Factors , Tumor Cells, Cultured , Tumor Suppressor Proteins/metabolism , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor CABSTRACT
OBJECTIVE: The efficacy of low-dose dexamethasone (DXM) therapy in patients with hormone-refractory prostate cancer (HRPC) was evaluated. PATIENTS AND METHODS: Prostate-specific antigen (PSA) response and survival following DXM therapy were analyzed in 27 Japanese patients exhibiting HRPC. Concurrent therapies and antiandrogen withdrawal syndrome, which may affect PSA levels and palliative effects, were excluded from the study. A dose of 1.5 mg of DXM was administered, and androgen deprivation therapy was maintained during DXM therapy. A decline in PSA levels of at least 50% from baseline was considered a significant PSA response. Prognostic factors for PSA response and survival were examined by univariate and multivariate analyses. RESULTS: A significant PSA response was observed in 16 of the 27 cases (59.3%). Median survival period of patients exhibiting significant PSA response was 15.9 months and was significantly longer than that of patients demonstrating a decline in PSA of less than 50% (median 7.7 months, p < 0.0001). Effect on pain control also correlated with the significant PSA response. No meaningful prognostic factors for PSA response were detected; however, a PSA decline of greater than 50% was the prognostic factor for survival. CONCLUSION: DXM therapy remains one of the most beneficial treatment modalities in patients with HRPC.
