Expression and somatic mutation on androgen receptor gene in prostate cancer

BACKGROUND: Lack of androgen receptor (AR) expression or mutation on the AR gene creates the tendency for androgen independence and progression of prostate cancer. However, the association between the progression and AR expression or mutations is still controversial. In this study, we evaluated the prognostic significance of AR expression and mutations in prostate cancers. METHODS: Forty-two prostate adenocarcinomas and three lymph node metastatic lesions sampled prior to hormonal therapy were included in this study; AR expression was analyzed immunohistochemically using an antibody against AR and the result was scored as the percentage of AR-positive tumor cells in the total tumor cells. Polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing were used to detect AR mutations. RESULTS: Our study revealed the average AR expression in the prostate adenocarcinoma was 52.2 +/- 27.1%, which was significantly lower than that in the adjacent non-tumorous prostate tissue (68.3 +/- 18.3% in average) (P < 0.001). A significant correlation was obtained between progression-free survival and AR expression (P < 0.01). By SSCP analysis, three silent mutations (T649T, E709E and E711E) were detected in three separate prostate carcinomas. CONCLUSION: : We conclude that AR expression is a useful prognostic indicator for tumor progression. Androgen receptor mutation may be an uncommon molecular event in untreated prostate cancer in Japanese men.     

Application of percutaneous endoscopic gastrostojejunostomy in a case of amyotrophic lateral sclerosis associated with the superior mesenteric artery syndrome

A 64‐year‐old woman who was diagnosed as suffering from amyotrophic lateral sclerosis (ALS) of bulbar type was admitted to our hospital for long‐term care. After admission, she underwent percutaneus endoscopic gastrostomy (PEG) and enteral feeding was initiated. However, the PEG alimentation was disrupted by aspiration pneumonia owing to the superior mesenteric artery syndrome (SMAS), diagnosed by gross anatomy and endoscopic studies. Conservative treatment for SMAS was not successful and sepsis developed. After recovery from this, an operation was recommended, but it was rejected by her and her family members. We therefore selected the method of placing a thin jejunostomy tube through the PEG, called percutaneous endoscopic gastrojejunostomy (PEGJ) and pulling it endoscopically into the proximal jejunum, thereby allowing delivery of nutrients. Thereafter, she was well and showed gradual improvement of nutritional parameters such as serum albumin and total cholesterol, as well as the lymphocyte subset. It is concluded that PEGJ is effective for long‐term enteral nutrition in ALS patients complicated with SMAS.     

Varicocele rupture due to sexual intercourse

Varicocele rupture was diagnosed in a 23-year-old man who presented with swelling and pain in the left scrotum after sexual intercourse. Color Doppler ultrasonography revealed blood flowing into the space surrounding the left testis, a hematoma and reflux of blood in the left spermatic vein. Varicocele rupture is a very rare condition and there have been only five reported cases.     

ALLELOTYPE OF ADENOMA AND DIFFERENTIATED ADENOCARCINOMA OF THE STOMACH

The molecular mechanism of gastric tumourigenesis has not yet been clarified, although investigators have postulated that differentiated adenocarcinoma may arise from pre-existing adenoma, similarly to the colorectal adenoma–carcinoma sequence. An allelotype analysis has been performed to identify chromosomal regions which are frequently deleted in gastric tumours and to examine the significance of the adenoma–carcinoma sequence in gastric tumourigenesis. Forty-five gastric tumours, 20 adenomas, and 25 differentiated adenocarcinomas were examined for loss of heterozygosity (LOH) using 39 microsatellite markers covering each non-acrocentric chromosome arm. Frequent LOH in the adenocarcinomas was observed on chromosomes 2q (33 per cent), 4p (33 per cent), 5q (50 per cent), 6p (33 per cent), 7q (43 per cent), 11q (36 per cent), 14q (38 per cent), 17p (45 per cent), 18q (36 per cent), and 21q (40 per cent). In contrast, the incidence of LOH in adenomas did not exceed 10 per cent at any of the loci examined. In addition to the p53 gene on 17p and the DCC gene on 18q, which are known to be frequently deleted in differentiated adenocarcinomas of the stomach, other unknown tumour suppressor genes on the above-mentioned chromosomes may also be inactivated. These observations suggest that the adenoma–carcinoma sequence is not a major pathway in gastric tumourigenesis.     

Effect of cyclosporin A on human bone marrow granulocyte-macrophage progenitors with anti-cancer agents

Cyclosporin A (CyA) overcomes P-glycoprotein (P-gp) associated multidrug resistance (MDR). P-gp expression is frequently observed among, not only various cancer cells, but also several normal tissues including bone marrow progenitor cells. These findings lead us to examine whether CyA enhances the myelotoxicity of anti-cancer agents. Bone marrow mononuclear cells were incubated with anti-cancer agents (vincristine, VCR; doxorubicin, ADM; etoposide, VP-16; cytarabine, Ara-C; methotrexate, MTX) and a concentration of CyA (0.5, 5.0 μg/mL). The methylcellulose assay for granulocyte-macrophage progenitors (CFU-GM) was conducted using the post-treated cells. There was no significant toxicity for marrow CFU-GM formation after 72 h incubation with CyA (84–108% of control). The inhibitory concentration that reduced colonies by 50% (IC₅₀) was 12 nmol/L for VCR, 6 nmol/L for ADM, 220 nmol/L for VP-16, 15 nmol/L for Ara-C and 35 nmol/L for MTX, respectively. For VCR, ADM and VP-16, the number of CFU-GM was unchanged with the addition of CyA at 0.5 μg/mL concentration. In contrast at 5 μg/mL CyA, the number of CFU-GM (% of control) was reduced significantly (P < 0.05 or P < 0.01). With MTX and Ara-C, the number of CFU-GM was unchanged after addition of CyA, even at 5 μg/mL concentration. We conclude CyA may therefore enhance cytotoxic drug sensitivity in MDR tumor cells at a clinically achievable concentration (0.5 μg/mL) without marrow toxicity.     

Factors affecting the efficiency of peripheral blood stem cell collection in children treated with chemotherapy and G-CSF

This retrospective study attempts to clarify the optimal timing for peripheral blood stem cell (PBSC) collection after conventional chemotherapy followed by granulocyte-colony stimulating factor (G-CSF) administration. Leukapheresis was performed 32 times in nine children with various cancers during bone marrow recovery phase following transient pancytopenia after chemotherapy. (On two occasions, leukapheresis was excluded because many leukemic blasts were included.) When the number of white blood cells (WBC) exceeded 1.8 times 10¹⁰/L after administration of G-CSF (200 μg/m², continuous infusion), many more CD34⁺ cells were contained in the collected peripheral mononuclear cells (P > 0.02) and a sufficient number of PBSC for transplantation (≥ 10 times 10⁸ CD34⁺ cells/kg) was obtained after one run in 15 of 17 leukapheresis sessions. In contrast, sufficient PBSC were obtained only in one of 13 runs of leukapheresis when the number of WBC was < 1.8 times 10¹⁰/L. The number of WBC on the day when PBSC were collected correlated with collected nuclear cell number (r = 0.60), but not with the CD34⁺ cell ratio. The ratio was higher only when both platelets and reticulocytes increased in parallel with WBC. We conclude that sufficient PBSC collection is possible after conventional chemotherapy using G-CSF, when hematopoietic recovery is parallel, without the use of high-dose chemotherapy.     

Clinical significance of serum hyaluronic acid as a fibrosis marker in chronic hepatitis C patients treated with interferon-α: Histological evaluation by a modified histological activity index scoring system

Abstract The aim of the present study was to investigate the histological changes effected by interferon (IFN) treatment and to evaluate the clinical significance of serum hyaluronic acid (HA) as a marker of fibrosis. Forty-nine patients with chronic hepatitis C treated with IFN-α were divided into three groups according to the existence of viraemia: sustained complete responders (CR), complete responders with relapse (PR) and non-responders (NR). Needle biopsy sections of the liver taken before and at the end of IFN treatment were assessed according to the modified histological activitindex (HAI) scoring system. Serum fibrosis markers, including HA, were measured at needle biopsies. Biopsies of CR at the end of treatment showed a significant improvement in fibrosis and necroinflammatory scores. More significant correlation was observed between fibrosis scores and serum levels of HA before IFN treatment (r= 0.607, P < 0.0001) than those between fibrosis scores, on the one hand, and pepride of type III procollagen (PIIIP; r= 0.531, P= 0.0004) or type IV collagen 7S domain (type IV-C; r= 0.241, P= 0.1062) on the other. Moreover, serum HA levels fell significantly in patients in whom fibrosis improved (P= 0.011). This is the first paper describing the advantages of the modified HAI scoring system over others in estimating the effect of IFN-α; the results also indicate that serum HA can be useful in monitoring liver fibrosis in chronic hepatitis C patients treated with IFN-α.