A morpho-molecular prognostic model for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third common cause of cancer-related deaths and its prognostication is still suboptimal. The aim of this study was to establish a new prognostication algorithm for HCC.

An ultrastructural study of retinal photoreceptor degeneration associated with bronchial carcinoma

We studied both eyes of a 66-year-old man with retinal degeneration and oat cell carcinoma of the bronchus. Retinal degeneration was most marked peripheral to the parafovea where photoreceptor cells and their outer segments were absent. Within the parafovea, photoreceptor cells remained but rod outer segments were absent and cone outer segments were fragmented and disorganized. The retinal pigment epithelium contained many immature melanin granules within melanolysosomes, suggesting abnormal melanin synthesis and resorption. We suggest that a pharmacologically active substance resembling a hormone produced by the tumor increased melanin synthesis in the pigment epithelium and that the increased melanin content in these cells compromised their ability to phagocytose and maintain normal turnover of photoreceptor outer segments. We believe these changes led to photoreceptor outer segment loss and subsequent degeneration of the photoreceptor cells.

Dietary Carbohydrate Intake, Glycemic Index, and Glycemic Load and Endometrial Cancer Risk: A Prospective Cohort Study

Endometrial cancer risk has been directly associated with glycemic load. However, few studies have investigated this link, and the etiological role of specific dietary carbohydrate components remains unclear. Our aim was to investigate associations of carbohydrate intake, glycemic index, and glycemic load with endometrial cancer risk in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Recruitment took place in 1993-2001. Over a median of 9.0 years of follow-up through 2009, 386 women developed endometrial cancer among 36,115 considered in the analysis. Dietary intakes were assessed using a 124-item diet history questionnaire. Cox proportional hazards models were applied to calculate hazard ratios and 95% confidence intervals. Significant inverse associations were detected between endometrial cancer risk and total available carbohydrate intake (hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.49, 0.90), total sugars intake (HR = 0.71, 95% CI: 0.52, 0.96), and glycemic load (HR = 0.63, 95% CI: 0.46, 0.84) when women in the highest quartile of intake were compared with those in the lowest. These inverse associations were strongest among overweight and obese women. No associations with endometrial cancer risk were observed for glycemic index or dietary fiber. Our findings contrast with previous evidence and suggest that high carbohydrate intakes and glycemic loads are protective against endometrial cancer development. Further clarification of these associations is warranted.

Management of Bartholin's gland carcinoma using high-dose-rate interstitial brachytherapy boost

To describe the patterns of use, clinical outcomes, and dose-volume histogram parameters of high-dose-rate interstitial brachytherapy (HDR-ISBT) in the management of Bartholin's gland cancer.

Expression of transketolase-like 1 protein (TKTL1) in human endometrial cancer

Malignant tumors metabolize glucose to lactate even in the presence of oxygen (aerobic glycolysis). The metabolic switch from oxidative glycolysis to non-oxidative fermentation of glucose and proteins performed by the tumor cells seems to be associated with TKTL1 and pAkt overexpression. Therefore the aim of the present study was to investigate the expression of TKTL1 and pAkt in human specimens of endometrial cancer as compared to benign endometrium. Additionally, expression of the glucose transporter GLUT1 was also investigated as aerobic glycolysis is associated with an increased need for glucose.

Perifosine inhibits growth of human experimental endometrial cancers by blockade of AKT phosphorylation

Perifosine is an orally active alkylphospholipid analog, which has shown anti-tumor activity in a variety of cancers by inhibition of AKT phosphorylation. The objective of the current study was to evaluate its efficacy in in vitro models of human endometrial cancer.

The BTA stat test:A tumor marker for the detection of upper tract transitional cell carcinoma

Objectives. To conduct a prospective evaluation to determine the utility of the BTA stat test in the detection of upper tract transitional cell carcinoma (UTTCC). Monitoring for UTTCC currently relies on invasive procedures such as upper tract imaging, ureteral washing cytology (UWC) and/or ureteroscopy, or voided urine cytology (VUC). The BTA stat test is a sensitive qualitative immunoassay that detects human complement factor H-related protein in voided urine.

Methods. A total of 81 patients participated, 27 with histopathologically confirmed UTTCC, 26 with upper tract calculi, and 28 with microscopic hematuria but no evidence of urologic disease. Voided specimens collected before surgery or treatment were tested with the BTA stat test and VUC. UWC was performed in specimens collected by a ureteral catheter.

Results. The BTA stat test was significantly more sensitive and specific than VUC or UWC. The overall sensitivity for each was 82%, 11%, and 48%; the specificity was 89%, 54%, and 33%. The positive predictive value for the BTA stat test was 79% and the negative predictive value was 91%, both the highest of the three tests.

Conclusions. The BTA stat test was superior to VUC and UWC in the detection of UTTCC. These results may support the adoption of a less aggressive follow-up policy when monitoring for UTTCC when the BTA stat result is negative. If cystoscopy is negative and the BTA stat test is positive, upper tract investigations should be expedited and, if the bladder is in place, bladder biopsies performed. (C) 2001, Elsevier Science Inc.

Contractile properties of human renal cell carcinoma recruited arteries and their response to nicotinamide

Background and purpose: The manipulation of tumour blood supply and thus oxygenation is a potentially important strategy for improving the treatment of solid tumours by radiation. Increased knowledge about the characteristics that distinguish the tumour vasculature from its normal counterparts may enable tumour blood flow to be more selectively modified, Nicotinamide (NA) causes relaxation of preconstricted normal and tumour-supply arteries in rats. It has also been shown to affect microregional blood flow in human tumours. Direct effects of NA on human tumour supply arteries have not previously been reported. This paper describes our evaluation of the effects of NA on two parameters: 'spontaneous', oscillatory contractile activity and agonist (phenylephrine)-induced constriction in the arteries supplying human renal cell carcinomas.

Materials and methods: Isolated renal cell carcinoma feeder vessels were perfused in an organ bath with the alpha(1)-adrenoceptor agonist phenylephrine (PE). When the arteries had reached a plateau of constriction, nicotinamide (8.2 mM) was added to the perfusate and changes in perfusion pressure were measured.

Results: PE (10 mu M) induced a sustained constriction in the majority of the renal cell carcinoma feeder vessels examined, demonstrating that they retain contractile characteristics, at least in response to this alpha(1)-adrenoceptor agonist. In combination with NA (8.2 mM) the constriction was significantly attenuated in half of the preparations. In addition, seven arteries exhibited spontaneous contractile activity which was significantly attenuated by NA in six of them.

Conclusions: NA can significantly attenuate both 'spontaneous' and agonist-induced constrictions in tumour-recruited human arteries, though not all arteries are sensitive. Published by Elsevier Science Ireland Ltd.

Two potential clinical applications of the alkaline single-cell gel electrophoresis assay .1. Human bladder washings and transitional cell carcinoma of the bladder .2. Human sperm and male infertility

Part 1: The alkaline single-cell gel electrophoresis (comet) assay was used to analyse the integrity and DNA content of exfoliated cells extracted from bladder washing specimens from 9 transitional cell carcinoma patients and 15 control patients. DNA damage, as expressed by % tail DNA and tail moment values, was observed to occur in cells from both control and bladder cancer samples. The extent of the damage was, however, found to be significantly greater in the cancer group than in the control group. Comet optical density values were also recorded for each cell analysed in the comet assay and although differences observed between tumour grades were not found to be statistically significant, the mean comet optical density value was observed to be greater in the cancer group than in the control population studied, These preliminary results suggest that the comet assay may have potential as a diagnostic tool and as a prognostic indicator in transitional cell carcinoma, Part 2: Baseline DNA damage in sperm cells from 13 normozoospermic fertile males, 17 normozoospermic infertile males and 11 asthenozoospermic infertile males were compared using a modified alkaline comet assay technique. No significant difference in the level of baseline DNA damage was observed between the 3 categories of sperm studied; however the untreated sperm cells were observed to display approximately 20% tail DNA. This is notably higher than the background DNA damage observed in somatic cells where the % tail DNA is normally less than 5%. Sperm from the 3 groups of men studied were also compared for sensitivity to DNA breakage, using the modified alkaline comet assay, following X-ray irradiations (5, 10 and 30 Gy) and hydrogen peroxide treatments (40, 100 and 200 mu M). Significant levels of X-ray-induced damage were found relative to untreated control sperm in the two infertile groups following 30 Gy irradiation. Significant damage in hydrogen peroxide-treated sperm was observed in sperm from fertile samples, at 200 mu M and in infertile samples at 100- and 200-mu M doses relative to controls. These results therefore indicate that fertile sperm samples are more resistant to X-ray- and hydrogen peroxide-induced DNA breakage than infertile samples. Further studies involving greater numbers of individuals are currently in progress to confirm these findings.