Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer.

BACKGROUND: We prospectively examined influence of androgen deprivation therapy (ADT) on lipid and glucose metabolisms in Japanese patients with prostate cancer. METHODS: Patients with prostate cancer who were hormone-naive and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight, abdominal circumference and blood testing associated with lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat before and after 1 year of ADT. ADT was limited to a luteinizing hormone-releasing hormone (LHRH) agonist with or without bicalutamide. RESULTS: Of 218 patients registered, data were available from 177 patients who completed 1 year of ADT. Of these, CT was performed before and after 1 year of ADT in 88 patients. Median age was 75 years (range, 49-85 years). Median PSA before ADT was 16.7 ng ml(-1) (range, 0.3-3316). Clinical stage was B (54.2%), C (23.2%) and D (20.9%). Mean increases in body weight and abdominal circumference after 1 year of ADT were 2.9 and 3.0%, respectively. Mean increases in total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were 10.6, 14.3, 7.8 and 16.2%, respectively. Mean increases in fasting blood sugar and hemoglobin A1c (HbA1c) were 3.9 and 2.7%, respectively. Lipid alterations were noted in patients without comorbidities, whereas changes in HbA1c were noted in patients with diabetes mellitus at baseline. These lipid and glucose alterations were prominent in the early ADT period. Both visceral and subcutaneous fat, as measured by CT, increased by >20%. The increase in subcutaneous fat was significantly greater than that in visceral fat (P=0.028). CONCLUSIONS: One year of ADT significantly changed lipid and glucose metabolism in Japanese patients with prostate cancer. Patient characteristics or comorbidities at baseline may be associated with ADT-induced metabolic changes.

Experimental validation of a linear model for data reduction in chirp-pulse microwave CT.

Chirp-pulse microwave computerized tomography (CP-MCT) is an imaging modality developed at the Department of Biocybernetics, University of Niigata (Niigata, Japan), which intends to reduce the microwave-tomography problem to an X-ray-like situation. We have recently shown that data acquisition in CP-MCT can be described in terms of a linear model derived from scattering theory. In this paper, we validate this model by showing that the theoretically computed response function is in good agreement with the one obtained from a regularized multiple deconvolution of three data sets measured with the prototype of CP-MCT. Furthermore, the reliability of the model as far as image restoration in concerned, is tested in the case of space-invariant conditions by considering the reconstruction of simple on-axis cylindrical phantoms.

Image restoration in chirp-pulse microwave CT (CP-MCT).

Chirp-pulse microwave computed tomography (CP-MCT) is a technique for imaging the distribution of temperature variations inside biological tissues. Even if resolution and contrast are adequate to this purpose, a further improvement of image quality is desirable. In this paper, we discuss the blur of CP-MCT images and we propose a method for estimating the corresponding point spread function (PSF). To this purpose we use both a measured and a computed projection of a cylindrical phantom. We find a good agreement between the two cases. Finally the estimated PSF is used for deconvolving data corresponding to various kinds of cylindrical phantoms. We use an iterative nonlinear deconvolution method which assures nonnegative solutions and we demonstrate the improvement of image quality which can be obtained in such a way.

Isolation and characterization of the novel gene, TU3A, in a commonly deleted region on 3p14.3-->p14.2 in renal cell carcinoma.

We previously identified a 700-kb region of common allelic loss on 3p14.3-->p14.2 in renal cell carcinoma (RCC). We further analyzed this region and constructed a sequence ready bacterial artificial chromosome (BAC) contig. This region was totally covered by six overlapping BAC clones and was roughly estimated to be 700 kb. Furthermore, we isolated a gene in this region that we termed TU3A. This gene encodes a protein consisting of 144 amino acids. Homology search did not show any significant similarities with known genes or proteins. Northern analysis with normal tissue identified a 3.0-kb transcript that was expressed ubiquitously. Although our mutation search using 37 primary RCCs as well as five RCC cell lines failed to detect any somatic alterations in the TU3A gene, two of five RCC cell lines had totally lost its expression. Considering the fact that we found no genetic alterations in TU3A, it is possible that some epigenetic alteration may have suppressed its expression.

Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer.

Prostate cancer is a major cause of cancer death among elderly men in America, Europe, and Japan. However, the molecular mechanism of carcinogenesis is not yet well characterized. Frequent loss of heterozygosity (LOH) on chromosome 10q was reported in prostate cancer, and a candidate tumor suppressor gene, PTEN, was isolated on chromosome band 10q23.3. To investigate the genetic alterations of PTEN, we examined 45 primary prostate cancer specimens. LOH at the PTEN locus was observed in two (11.1%) of 18 tumors. However, no mutations were observed in any of the primary prostate cancers. These data suggest that mutation of the PTEN gene does not play a major role in prostate carcinogenesis of Japanese patients.

Identification of a 700-kb region of common allelic loss in chromosome bands 3p14.3-p21.1 in human renal cell carcinoma.

The short arm of chromosome 3 is considered to harbor one or more of the tumor suppressor genes taking part in the genesis of renal cell carcinoma (RCC). To define the localization of such putative tumor suppressor gene(s), we studied specific allelic loss on chromosome 3p by using 84 samples of RCC with nine microsatellite markers. We defined two commonly deleted regions in 3p14.3-p21.2: (1) region A, a 2-cM region between D3S1313 and D3S1592, and (2) region B, a 2-cM region between D3S1581 and D3S1289. The most frequent loss of heterozygosity was observed at D3S1067 (33 of 59, 55.9%), which is within region A. We further focused on region A and constructed a yeast artificial chromosome (YAC) contig and found that one YAC clone, which was 700-kb in size, harbored the entire region A. Using cosmid clones isolated from this contig, we also performed fluorescence in situ hybridization analysis and found that two of the tumors were homozygously deleted in this region. Our results strongly suggest the existence of a tumor suppressor gene in this region.

Infrequent genetic alterations of the PTEN/MMAC1 gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary.

In the present study, we searched for genetic alterations of the entire coding region of PTEN/MMAC1, a recently isolated candidate tumor suppressor gene, in 178 specimens from Japanese patients with various malignant tumors by the polymerase chain reaction-single strand conformation polymorphism method. The samples consisted of 11 glioblastoma multiformes (GBMs), 14 astrocytomas, 47 breast cancers, 25 non-small cell lung cancers, 9 small cell lung cancers, 8 pancreatic cancers, 24 renal cell carcinomas, 20 ovarian cancers, and 20 metastatic lung tumors from various organs. Only one somatic frameshift mutation at codon 319 was observed in one (9%) of eleven GBMs. Our results suggest that mutation of the PTEN/MMAC1 gene does not play a major role in carcinogenesis, at least in the tumor types from Japanese patients analyzed in this study.

[Eighteen cases of multicystic kidney: natural history and renal function of the contralateral kidney].

PURPOSE: The objective of this study is to evaluate natural history of multicystic kidney (MCK) and renal function of the contralateral kidney. METHODS: We analyzed 18 children (7 boys and 11 girls) with unilateral MCK. The sizes of cysts were investigated by ultrasonography. Urinary beta 2-microgloblin (beta 2 m), alpha 1-microgloblin (alpha 1 m) and N-acetyl-beta-D-glucosaminidase (NAG) and albumin were determined as markers of tubular and glomerular damage. The renal function was evaluated by 99m Tc-dimercaptosuccinic acid (99 m Tc-DMSA) renal uptake rate. RESULTS: Nephrectomy was performed in 2 children. In 14 (87.5%) of 16 cases who were followed conservatively, the size of cysts was spontaneously reduced by 1-18 months (mean 6.4). Neither hypertension nor malignancy from the affected kidney has been observed in follow-up periods of 6-63 months. One patient had minor degree of contralateral ureteral dilatation which resolved spontaneously. Lower DMSA uptake rate of contralateral kidney was demonstrated in 63% (10/16). Markers of tubular damage were abnormally high in these patients. CONCLUSION: From these results, the most appropriate management of MCK is conservative with ultrasonic monitoring. Long-term follow-up testings with special care on contralateral renal function will be necessary because the overload to the contralateral healthy kidney may have already occurred during infancy and cause focal glomerulosclerosis and renal failure in future.

The destructive effects of sclerosant ethanolamine oleate on mammalian vessel endothelium.

Ethanolamine oleate (EO) used widely in sclerotherapy against esophageal varices was studied for its pharmacological effect on blood coagulation and vascular damage in animals. Blood coagulation was completely inhibited by EO at a concentration of 0.31%. EO destroyed the endothelial cells of the vessel of dog and rat within one minute after injection into the vessels. An accumulation of fibrin and platelets on the surface of the damaged vessel was observed electron microscopically. Mural thrombus was formed in a few hours and the thrombus occluded the blood stream in the vein. From these animal experiment, intravasal injection of EO was considered to cause the disappearance of varices by the following two processes: collapse of varices because of occlusion of the blood stream and shrinking of the obstructed thrombus through organization.

[Studies on the damage of the cultured endothelial cells and K-562 cells by sclerosants (ethanolamine oleate, Aethoxysklerol and absolute ethanol) used in the treatment of esophageal varices].

In injection sclerotherapy against esophageal varices, the damage of the endothelial cells of varices has been supposed to be most important for the formation of thrombi in the injected varices. Mechanisms of the destructive action of three sclerosants (ethanolamine oleate [EO], Aethoxysklerol [AS] & absolute ethanol [Et]) on endothelial cells of varices were studied by means of observation of morphological change of the cells and 51Cr release from the cells in a contact with these sclerosants using cultured human endothelial cells and culture cell line K-562 as target cells. Main mechanism for destructive action of EO on the endothelial cells was considered to be cytolysis through injury of cell membrane, since the cells disappeared immediately after addition of EO with marked release of 51Cr. The destructive action of AS on endothelial cells was considered to be mild cytolysis, since moderate destruction of the cells and moderate release of 51Cr were induced with AS. On the other hand, Et showed a fixative-destructive action on the cells without marked morphological change and with little release of 51Cr. Therefore, it was considered that EO and AS caused the damage of endothelial cells through their lytic action of the cell membrane, whereas Et caused it through the fixative action of the cell membrane.