Activities of bone morphogenetic proteins in prolactin regulation by somatostatin analogs in rat pituitary GH3 cells

Involvement of the pituitary BMP system in the modulation of prolactin (PRL) secretion regulated by somatostatin analogs, including octreotide (OCT) and pasireotide (SOM230), and a dopamine agonist, bromocriptine (BRC), was examined in GH3 cells. GH3 cells are rat pituitary somato-lactotrope tumor cells that express somatostatin receptors (SSTRs) and BMP system molecules including BMP-4 and -6. Treatment with BMP-4 and -6 increased PRL and cAMP secretion by GH3 cells. The BMP-4 effects were neutralized by adding a BMP-binding protein Noggin. These findings suggest the activity of endogenous BMPs in augmenting PRL secretion by GH3 cells. BRC and SOM230 reduced PRL secretion, but OCT failed to reduce the PRL level. In GH3 cells activated by forskolin, BRC suppressed forskolin-induced PRL secretion with reduction in cAMP levels. OCT did not affect forskolin-induced PRL level, while SOM230 reduced PRL secretion and PRL mRNA expression induced by forskolin. BMP-4 treatment enhanced the reducing effect of SOM230 on forskolin-induced PRL level while BMP-4 did not affect the effects of OCT or BRC. Noggin treatment had no significant effect on the BRC actions reducing PRL levels by GH3 cells. However, in the presence of Noggin, OCT elicited an inhibitory effect on forskolin-induced PRL secretion and PRL mRNA expression, whereas the SOM230 effect on PRL reduction was in turn impaired. It was further found that BMP-4 and -6 suppressed SSTR-2 but increased SSTR-5 mRNA expression of GH3 cells. These findings indicate that Noggin rescues SSTR-2 but downregulates SSTR-5 by neutralizing endogenous BMP actions, leading to an increase in OCT sensitivity and a decrease in SOM230 sensitivity of GH3 cells. In addition, BMP signaling was facilitated in GH3 cells treated with forskolin. Collectively, these findings suggest that BMPs elicit differential actions in the regulation of PRL release dependent on cellular cAMP-PKA activity. BMPs may play a key role in the modulation of SSTR sensitivity of somato-lactotrope cells in an autocrine/paracrine manner

A Case of Traumatic Cyclodialysis Followed by Ultrasound Biomicroscopy

We report a case of persistent traumatic cyclodialysis treated bygoniophotocoagulation and observed by ultrasound biomicroscopy (UBM) throughout the course.A 16 year-old male was struck in his right eye by a rocket firework. After the injury,hypotony continued for 4 months and he was referred to Hiroshima University Hospital. Atthat time, the best visual acuity in his right eye was 0.2 and the intraocular pressure was6 mmHg. Three hundred and sixty degrees of cyclodialysis, partial peripheral anteriorsynechia, hypotony maculopathy and subretinal proliferative tissue were observed.Cyclodialysis was obvious by UBM. From 4 months after the injury goniophotocoagulation wasperformed six times in 2 months. Intraocular pressure recovered 6 months after the injuryand reattachment of cyclodialysis and disappearance of the suprachoroidal space wereconfirmed by UBM. UBM was useful in observing cyclodialysis throughout the course

Testicular seminoma after the complete remission of extragonadal yolk sac tumor : a case report

BACKGROUND: Between 2% and 5% of malignant germ-cell tumors in men arise at extragonadal sites. Of extragonadal germ cell tumors, testicular carcinoma in situ (CIS) are present in 31–42% of cases, and CIS are reported to have low sensitivity to chemotherapy in spite of the various morphology and to have a high likelihood of developing into testicular tumors. A testicular biopsy may thus be highly advisable when evaluating an extragonadal germ cell tumor. CASE PRESENTATION: A 36-year-old man was diagnosed as having an extragonadal non-seminomatous germ cell tumor, that was treated by cisplatin-based chemotherapy, leading to a complete remission. In the meantime, testicular tumors were not detected by means of ultrasonography. About 4 years later, a right testicular tumor was found, and orchiectomy was carried out. Microscopically, the tumor was composed of seminoma. CONCLUSIONS: We herein report a case of metachronous occurrence of an extragonadal and gonadal germ cell tumor. In the evaluation of an extragonadal germ cell tumor, a histological examination should be included since ultrasonography is not sufficient to detect CIS or minute lesions of the testis

Peritoneal dissemination of prostate cancer due to laparoscopic radical prostatectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Peritoneal dissemination with no further metastases of prostate cancer is very rare, with only three cases reported in the available literature. We report the first case of iatrogenic peritoneal dissemination due to laparoscopic radical prostatectomy.</p> <p>Case Presentation</p> <p>A 59-year-old Japanese man underwent laparoscopic radical prostatectomy for clinical T2bN0M0 prostate cancer, and the pathological diagnosis was pT3aN0 Gleason 3+4 adenocarcinoma with a negative surgical margin. Salvage radiation therapy was performed since his serum prostate-specific antigen remained at a measurable value. After the radiation, he underwent castration, followed by combined androgen blockade with estramustine phosphate and dexamethasone as each treatment was effective for only a few months to a year. Nine years after the laparoscopic radical prostatectomy, computed tomography revealed a peritoneal tumor, although no other organ metastasis had been identified until then. He died six months after the appearance of peritoneal metastasis. An autopsy demonstrated peritoneal dissemination of the prostate cancer without any other metastasis.</p> <p>Conclusion</p> <p>Physicians should take into account metastasis to unexpected sites. Furthermore, we suggest that meticulous care be taken not to disseminate cancer cells to the peritoneum during laparoscopic radical prostatectomy.</p

RAB35 is required for murine hippocampal development and functions by regulating neuronal cell distribution

RAB35 is a multifunctional small GTPase that regulates endocytic recycling, cytoskeletal rearrangement, and cytokinesis. However, its physiological functions in mammalian development remain unclear. Here, we generated Rab35-knockout mice and found that RAB35 is essential for early embryogenesis. Interestingly, brain-specific Rab35-knockout mice displayed severe defects in hippocampal lamination owing to impaired distribution of pyramidal neurons, although defects in cerebral cortex formation were not evident. In addition, Rab35-knockout mice exhibited defects in spatial memory and anxiety-related behaviors. Quantitative proteomics indicated that the loss of RAB35 significantly affected the levels of other RAB proteins associated with endocytic trafficking, as well as some neural cell adhesion molecules, such as contactin-2. Collectively, our findings revealed that RAB35 is required for precise neuronal distribution in the developing hippocampus by regulating the expression of cell adhesion molecules, thereby influencing spatial memory

Relationship between serum isoflavone concentrations and frequency of soybean products consumption in patients with prostate cancer

Dietary consumption of high concentrations of soybean products has been suggested to reduce the risk for prostate cancer (PCa). We conducted a survey using patients with PCa to assess the relationship between serum concentrations of isoflavone aglycones and frequency of soybean products consumption in patients with PCa. We measured the serum concentrations of daidzein, genistein, glycitein, and equol in 99 PCa patients, in addition to conducting a survey using a self administrated questionnaire that included the frequencies of various food item consumptions. If serum concentrations of equol were at a value less than 0.5 ng/mL, they were classified as an equol non producer, and the other patients were classified as equol producers. As a result, serum concentrations of daidzein, genistein, and glycitein were found to be significantly correlated to each other (P<0.001). The frequency of tofu (soybean curd) consumption was significantly correlated with the serum concentration of daidzein (P<0.05). Likewise, the frequency of natto (fermented soybean) consumption was significantly correlated with the serum concentrations of daidzein, genistein, and glycitein (P<0.01). In the study there were 40 equol producers and 59 equol non producers, but none of the food items were significantly different between the equol producers and the equol non producers. We have a plan to perform a similar survey for population based controls in the future. Comparisons between the data of the PCa patients and the controls would give us more information about the role of isoflavones and equol production in regard to the risk of PCa

Analysis of KIT, SCF, and Initial Screening of SLUG in Patients with Piebaldism

n/

Peroxisome proliferator-activated receptor activity is involved in the osteoblastic differentiation regulated by bone morphogenetic proteins and tumor necrosis factor-α.

Recent studies have suggested possible adverse effects of thiazolidinediones on bone metabolism. However, the detailed mechanism by which the activity of PPAR affects bone formation has not been elucidated. Impaired osteoblastic function due to cytokines is critical for the progression of inflammatory bone diseases. In the present study, we investigated the cellular mechanism by which PPAR actions interact with osteoblast differentiation regulated by BMP and TNF-alpha using mouse myoblastic C2C12 cells. BMP-2 and -4 potently induced the expression of various bone differentiation markers including Runx2, osteocalcin, type-1 collagen and alkaline phosphatase (ALP) in C2C12 cells. When administered in combination with a PPAR alpha agonist (fenofibric acid) but not with a PPAR gamma agonist (pioglitazone), BMP-4 enhanced osteoblast differentiation through the activity of PPAR alpha. The osteoblastic changes induced by BMP-4 were readily suppressed by treatment with TNF-alpha. Interestingly, the activities of PPAR alpha and PPAR gamma agonists reversed the suppression by TNF-alpha of osteoblast differentiation induced by BMP-4. Furthermore, TNF-alpha-induced phosphorylation of MAPKs, NF kappa B, I kappa B and Stat pathways was inhibited in the presence of PPAR alpha and PPAR gamma agonists with reducing TNF-alpha receptor expression. In view of the finding that inhibition of SAPK/JNK. Stat and NF kappa B pathways reversed the TNF-alpha suppression of osteoblast differentiation, we conclude that these cascades are functionally involved in the actions of PPARs that antagonize TNF-alpha-induced suppression of osteoblast differentiation. It was further discovered that the PPAR alpha agonist enhanced BMP-4-induced Smad1/5/8 signaling through downregulation of inhibitory Smad6/7 expression, whereas the PPAR gamma agonist impaired this activity by suppressing BMPRII expression. On the other hand, BMPs increased the expression levels of PPAR alpha and PPAR gamma in the process of osteoblast differentiation. Thus, PPAR alpha actions promote BMP-induced osteoblast differentiation, while both activities of PPAR alpha and PPAR gamma suppress TNF-alpha actions. Collectively, our present data establishes that PPAR activities are functionally involved in modulating the interaction between the BMP system and TNF-alpha receptor signaling that is crucial for bone metabolism