[Three cases of IgG4-related focal retroperitoneal fibrosis].

(Case 1) A 63-year-old man was diagnosed as retroperitoneal fibrosis by the exploratory laparotomy for the pelvic mass with high IgG4 levels. (Case 2) A 64-year-old man had past medical history of autoimmune pancreatitis which was treated by steroid use. Three years later, he was diagnosed as IgG4-related gallbladder tumor by the cholecystectomy.

Combined inhibition of Wee1 and Hsp90 activates intrinsic apoptosis in cancer cells.

Heat shock protein 90 (Hsp90) is an essential, evolutionarily conserved molecular chaperone. Cancer cells rely on Hsp90 to chaperone mutated and/or activated oncoproteins, and its involvement in numerous signaling pathways makes it an attractive target for drug development. Surprisingly, however, the impact of Hsp90 inhibitors on cancer cells is frequently cytostatic in nature, and efforts to enhance the antitumor activity of Hsp90 inhibitors in the clinic remain a significant challenge.

Methoxychalcone inhibitors of androgen receptor translocation and function.

Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we report methoxychalcones that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non-responsive state, thus demonstrating a novel chemical scaffold for antiandrogen development and a unique mechanism of antiandrogen activity.

Perioperative complications of radical cystectomy after induction chemoradiotherapy in bladder-sparing protocol against muscle-invasive bladder cancer: a single institutional retrospective comparative study with primary radical cystectomy.

Objective: To compare rates of early morbidity after radical cystectomy in patients treated with or without induction chemoradiotherapy (CRT) using a standardized reporting methodology.

Methods: All 193 consecutive patients undergoing radical cystectomy for bladder cancer between 1989 and 2010 were retrospectively reviewed. Induction chemoradiotherapy consists of radiation at 40 Gy to the small pelvis and two cycles of concurrent cisplatin at 20 mg/day for 5 days.

Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells.

Drugs that target novel surfaces on the androgen receptor (AR) and/or novel AR regulatory mechanisms are promising alternatives for the treatment of castrate-resistant prostate cancer. The 52 kDa FK506 binding protein (FKBP52) is an important positive regulator of AR in cellular and whole animal models and represents an attractive target for the treatment of prostate cancer. We used a modified receptor-mediated reporter assay in yeast to screen a diversified natural compound library for inhibitors of FKBP52-enhanced AR function.

A novel repeat biopsy nomogram based on three-dimensional extended biopsy.

Objectives: To develop a nomogram based on a cohort examined with 3-dimensional (3D) protocol for diagnosis of prostate cancer on repeat biopsy.

Methods: Of 4074 consecutive men undergoing prostate biopsy at our institutions between 2000 and 2009, 775 men with at least 1 previous negative biopsy underwent repeat biopsy with a 3D protocol. Men with previous atypical glands or atypical small acinar proliferation and/or without available prostate-specific antigen (PSA) kinetics information were excluded.

Simple prophylactic procedure of inguinal hernia after radical retropubic prostatectomy: isolation of the spermatic cord.

To reduce the incidence of inguinal hernia (IH) after radical retropubic prostatectomy (RRP), a simple prophylactic procedure was carried out during RRP. A consecutive 82 patients who had undergone RRP for clinically localized prostate cancer between July 2002 and October 2006 at Toride Kyodo General Hospital were enrolled. From July 2002 to November 2003, 20 patients underwent conventional RRP.

[Primary adenocarcinoma of the female urethra treated by multimodal therapy].

A 64-year old female presented with urinary retention. Physical examination revealed a firm mass on the anterior vaginal wall. Magnetic resonance imaging showed a tumor surrounding the urethra, which invaded to the vesical triangle and the anterior vaginal wall.

Glucocorticoids suppress tumor lymphangiogenesis of prostate cancer cells.

Purpose: Glucocorticoids such as prednisone, hydrocortisone, and dexamethasone are known to provide some clinical benefit for patients with hormone-refractory prostate cancer. However, the underlying mechanisms by which glucocorticoids affect hormone-refractory prostate cancer progression are not well established as yet. Our previous study has shown that glucocorticoids inhibit tumor angiogenesis possibly by down-regulation of vascular endothelial growth factor (VEGF) and interleukin 8.

Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells.

Purpose: Glucocorticoids, such as prednisone, hydrocortisone, and dexamethasone, are known to produce some clinical benefit for patients with hormone-refractory prostate cancer (HRPC). However, the underlying mechanisms by which glucocorticoids affect HRPC growth are not well established as yet. Here, we hypothesize that the therapeutic effect of glucocorticoids on HRPC can be attributed to a direct inhibition of angiogenesis through the glucocorticoid receptor by down-regulating two major angiogenic factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8).

Suppression of VEGF transcription in renal cell carcinoma cells by pyrrole-imidazole hairpin polyamides targeting the hypoxia responsive element.

Hypoxia inducible factor (HIF), a master regulator of critical genes for cell survival under hypoxic conditions, is known to be related to tumorigenesis and progression of renal cell carcinoma. N-methylpyrrole (Py)-N-methylimidazole (Im) hairpin polyamides are synthetic organic compounds that recognize and bind to the minor grooves of specific DNA sequences. We synthesized three Py-Im hairpin polyamides targeting the flanking sequences of hypoxia responsive element (HRE; a binding site of HIF) in the promoter region of the vascular endothelial growth factor (VEGF) gene.

[A case of idiopathic retroperitoneal fibrosis accompanied by asynchronous bilateral urinoma].

The patient was a 68-year-old female with the complaint of left flank pain. On examination, hydronephrosis of the left kidney and the urinoma of left retroperitoneal space were disclosed by abdominal computed tomographic (CT) scan. The urinoma disappeared spontaneously, but 4 months later right hydronephrosis and the urinoma of ipsilateral retroperitoneum emerged.

Hypotaurocyamine kinase evolved from a gene for arginine kinase.

Hypotaurocyamine kinase (HTK) is a member of the highly conserved family of phosphagen kinases that includes creatine kinase (CK) and arginine kinase (AK). HTK is found only in sipunculid worms, and it shows activities for both the substrates hypotaurocyamine and taurocyamine. Determining how HTK evolved in sipunculids is particularly insightful because all sipunculid-allied animals have AK and only some sipunculids have HTK.

Down-regulation of vascular endothelial growth factor in renal cell carcinoma cells by glucocorticoids.

Metastatic renal cell carcinomas (RCC) remain highly resistant to systemic therapy. RCCs are highly vascular tumors, which overproduce angiogenic peptides such as vascular endothelial growth factor (VEGF) even under normoxic conditions. A potential suggested role of antiangiogenic therapeutic strategies is the treatment of RCC by inhibiting VEGF production.

p51/p63 Controls subunit alpha3 of the major epidermis integrin anchoring the stem cells to the niche.

p51/p63, a member of the tumor suppressor p53 gene family, is crucial for skin development. We describe here identification of ITGA3 encoding integrin alpha(3) as a target of its trans-activating function, proposing that p51/p63 allows epidermal stem cells to express laminin receptor alpha(3)beta(1) for anchorage to the basement membrane. When activated by genotoxic stress or overexpressed ectopically in non-adherent cells, p51/p63 transduced a phenotype to attach to extracellular matrices, which was accompanied by expression of ITGA3.

[A case bilharziasis in a Japanese male].

Bilharziasis is an endemic disease distributed mostly in African countries and the Middle East, and causes severe disturbances of urinary tract secondarily. Although it used to be a very rare disease in Japan, modern human mobility and jet travel have brought this tropical disease into our country far from endemic areas. A 25-year-old Japanese male presented to our hospital with macroscopic hematuria.

C-H to N substitution dramatically alters the sequence-specific DNA alkylation, cytotoxicity, and expression of human cancer cell lines.

We designed and synthesized sequence-specific alkylating conjugates 1 and 2, which selectively alkylate matched sequences at nanomolar concentrations. Conjugates 1 and 2 differ only in that the C-H is substituted by an N in the second ring, which precisely recognizes and effectively alkylates DNA according to the recognition rule of Py-Im polyamides. We investigated sequence-specific DNA alkylation, cytotoxicity in 39 human cancer cell lines, and the effect on expression levels in cancer cell lines by Py-Im conjugates 1 and 2.

Prognostic significance of endothelial Per-Arnt-sim domain protein 1/hypoxia-inducible factor-2alpha expression in a subset of tumor associated macrophages in invasive bladder cancer.

Purpose: Endothelial Per-Arnt-Sim domain protein 1 (EPAS1) is induced under hypoxia and it transactivates a series of genes involved in angiogenesis and energy metabolism. Recent studies showed that EPAS1 is expressed in tumor associated macrophages (TAMs), which have multifaceted roles in tumor progression. We hypothesized that EPAS1 expressed in TAMs may contribute to bladder cancer progression.

Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder.

Purpose: p63 is proposed to play roles in normal development and differentiation of stratified epithelia including urothelium. We recently reported that impaired p63 expression is a common feature of high-grade invasive urothelial carcinomas and associates with reduced beta-catenin. On the basis of these facts, we proposed that impaired p63 expression contributes to biological aggressiveness of urothelial neoplasms.