Role of KIT-Positive Interstitial Cells of Cajal in the Urinary Bladder and Possible Therapeutic Target for Overactive Bladder

In the gastrointestinal tract, interstitial cells of Cajal (ICCs) act as pacemaker cells to generate slow wave activity. Interstitial cells that resemble ICCs in the gastrointestinal tract have been identified by their morphological characteristics in the bladder. KIT is used as an identification marker of ICCs. ICCs in the bladder may be involved in signal transmission between smooth muscle bundles, from efferent nerves to smooth muscles, and from the urothelium to afferent nerves. Recent research has suggested that not only the disturbance of spontaneous contractility caused by altered detrusor ICC signal transduction between nerves and smooth muscle cells but also the disturbance of signal transduction between urothelial cells and sensory nerves via suburothelial ICC may induce overactive bladder (OAB). Recent reports have suggested that KIT is not only a detection marker of these cells, but also may play a crucial role in the control of bladder function. Research into the effect of a c-kit receptor inhibitor, imatinib mesylate, on bladder function implies that KIT-positive ICCs may be therapeutic target cells to reduce bladder overactivity and that the blockage of c-kit receptor may offer a new therapeutic strategy for OAB treatment, although further study will be needed

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Long-Term Survival of a Patient with Invasive Signet-Ring Cell Carcinoma of the Urinary Bladder Managed by Combined S-1 and Cisplatin Adjuvant Chemotherapy

Primary signet-ring cell carcinoma of the urinary bladder is extremely rare and patient survival is very poor. The disease usually presents at advanced stages because the cancer progresses rapidly. The only option for effective treatment is radical cystectomy, and no effective chemotherapy has been established for this variant. We report a case of signet-ring cell carcinoma of the urinary bladder with a long-term survival of 90 months owing to radical cystectomy and combination adjuvant chemotherapy with S-1 and cisplatin. To our knowledge, this is the first report to demonstrate the long-term therapeutic activity of combination S-1 and cisplatin adjuvant chemotherapy against invasive signet-ring cell carcinoma of the urinary bladder

Adrenal Neuroblastoma in an Adult: Effect of Radiotherapy on Local Progression after Surgical Removal

Here, we report the case of a 62-year-old man with neuroblastoma, which is extremely rare in adults. His tumor was resected, but it recurred four months later. Radiotherapy reduced tumor size, and the patient remained in good health three years after surgical tumor removal. The residual tumor and the treatments administered to this patient were evaluated. We have also reviewed the literature

Effect of Adiponectin on Kidney Crystal Formation in Metabolic Syndrome Model Mice via Inhibition of Inflammation and Apoptosis

<div><p>The aims of the present study were to elucidate a possible mechanism of kidney crystal formation by using a metabolic syndrome (MetS) mouse model and to assess the effectiveness of adiponectin treatment for the prevention of kidney crystals. Further, we performed genome-wide expression analyses for investigating novel genetic environmental changes. Wild-type (+/+) mice showed no kidney crystal formation, whereas ob/ob mice showed crystal depositions in their renal tubules. However, this deposition was remarkably reduced by adiponectin. Expression analysis of genes associated with MetS-related kidney crystal formation identified 259 genes that were >2.0-fold up-regulated and 243 genes that were <0.5-fold down-regulated. Gene Ontology (GO) analyses revealed that the up-regulated genes belonged to the categories of immunoreaction, inflammation, and adhesion molecules and that the down-regulated genes belonged to the categories of oxidative stress and lipid metabolism. Expression analysis of adiponectin-induced genes related to crystal prevention revealed that the numbers of up- and down-regulated genes were 154 and 190, respectively. GO analyses indicated that the up-regulated genes belonged to the categories of cellular and mitochondrial repair, whereas the down-regulated genes belonged to the categories of immune and inflammatory reactions and apoptosis. The results of this study provide compelling evidence that the mechanism of kidney crystal formation in the MetS environment involves the progression of an inflammation and immunoresponse, including oxidative stress and adhesion reactions in renal tissues. This is the first report to prove the preventive effect of adiponectin treatment for kidney crystal formation by renoprotective activities and inhibition of inflammation and apoptosis.</p></div

Confirmation of selected genes detected by microarray analysis.

<p>A–F. Among the selected genes with significant expression changes in the microarray analysis, the expression of several characteristic genes belonging to 6 categories based on GO analysis was evaluated by immunohistochemical staining. Magnification is ×20 (in box: ×400). 6 categories are as follows. A. Inflammation and immune-related gene group: LYZ1, Lysozyme 1.CD44, CD44 antigen; MHC-class 2, major histocompatibility complex-class2. B. Apoptosis-related gene group: STAT3, signal transducer and activator of transcription 3; AURKA, aurora kinase A, Thymidine kinase 1, C. Cell repair and proliferation-related gene group: MCM5, minichromosome maintenance deficient 5. D. Adhesion and fibrosis-related gene group: Fn, Fibronectin. E. Oxidative stress-related gene group: 8OHdG, 8-Hydroxydeoxyguanosine. F: transporter-related gene group; SLC12A1, solute carrier family 12, member 1.</p

Detection and quantification of calcium oxalate kidney crystal formation.

<p>A. Kidney sections of wild type (+/+), obesity (ob/ob), and adiponectin-treated ob/ob (ob/ob+APN) mice at day 6. The upper images show calcium oxalate crystal deposits in Pizzolato-stained sections. The lower images show non-stained sections observed by polarized light optical microphotography (PLOM). Magnification is ×20 (in box: ×400). B. Quantification of kidney crystals in +/+, ob/ob, and ob/ob+APN mice. Data are indicated as the mean ± SD. a; p = 0.0004, b; p = 0.005.</p

TUNEL staining and the number of TUNEL-positive cells.

<p>Data are indicated as the mean ± SD. *, p<0.05 between groups at the same time. **, p<0.01 between groups at the same time point. †, p<0.01 compared with the same group at day 6.</p

Expression analyses of <i>Spp1</i>, <i>Sod2</i>, <i>Ccl2</i>, and <i>Adipoq</i>.

<p>A. The results of quantitative PCR for the expression of <i>Spp1</i>, <i>Sod2</i>, <i>Ccl2</i>, and <i>Adipoq</i>. Expression levels are expressed relative to <i>Actb</i> (<i>actin-beta</i>) transcript levels. <i>Spp1</i>, secreted phosphoprotein 1; <i>Ccl2</i>, C-c chemokine ligands 2; <i>Sod2</i>, superoxide dismutase 2; <i>Adipoq</i>, adiponectin. Data are indicated as the mean ± SE. *, p<0.05 between groups at the same time point. †, p<0.01 compared with the same group at day 0. B. Immunohistochemical staining for OPN, MCP-1, SOD, and APN expression. OPN, osteopontin; MCP-1, monocyte chemotactic protein-1; SOD, superoxide dismutase; APN, adiponectin. Magnification is ×20 (in box: ×400). C. The quantification of immunohistochemical staining. Data are indicated as the mean ± SD. *, p<0.05 between groups at the same time point. †, p<0.05 compared with the same group at day 0.</p