Preferred Orientation of Hydroxyapatite Ceramics Along the -Axis Promotes Osteoblast Differentiation.

Hydroxyapatite (HAp) is similar to the main inorganic components of bone and tooth enamel. Furthermore, it possesses biocompatibility, making it suitable for clinical use in artificial bones. This study aimed to verify whether the preferred orientation of HAp influences osteogenesis.

Effect of bisphosphonate and denosumab treatment on TBS in Japanese breast cancer patients with AIBL.

Introduction: Bisphosphonates and denosumab increase bone mineral density (BMD) for osteoporosis treatment in patients with aromatase inhibitor-associated bone loss (AIBL). This study aimed to directly compare bisphosphonates with denosumab in treating patients with AIBL and to determine the effect of denosumab on the trabecular bone score (TBS).

Materials And Methods: Thirty-nine patients with AIBL receiving osteoporosis treatment (21 in the bisphosphonates group and 18 in the denosumab group) were retrospectively evaluated for changes in lumbar spine and femoral BMD, lumbar spine bone quality (assessed by TBS), and blood bone metabolic markers.

Quality of life after living donor liver transplant for biliary atresia in Japan.

Background: Health-related quality of life (HRQOL) is an important outcome in solid organ transplantation. This study evaluated and explored the factors of generic and transplant-specific HRQOL in Japanese pediatric and adolescent patients with biliary atresia (BA) after living donor liver transplant (LDLT).

Methods: A cross-sectional survey using anonymous questionnaires was completed between April and July 2015.

The fiber optic system for the Advanced Topographic Laser Altimeter System (ATLAS) instrument.

The Advanced Topographic Laser Altimeter System (ATLAS) Instrument has been in integration and testing over the past 18 months in preparation for the Ice, Cloud and Land Elevation Satellite - 2 (ICESat-2) Mission, scheduled to launch in 2017. ICESat-2 is the follow on to ICESat which launched in 2003 and operated until 2009. ATLAS will measure the elevation of ice sheets, glaciers and sea ice or the "cryosphere" (as well as terrain) to provide data for assessing the earth's global climate changes.

Development of the Japanese version of the Pediatric Quality of Life Inventory Transplant Module.

Background: Health-related quality of life (HRQOL) is an important outcome in pediatric solid organ transplantation. Considering the emerging problems after transplantation, an evaluation of transplant-specific aspects of HRQOL is essential, but no validated HRQOL measure is available in Japan. The aim of this study was therefore to develop the Japanese version of the Pediatric Quality of Life Inventory (PedsQL) Transplant Module Child Self-Report and to investigate its feasibility, reliability, and validity.

[Application of biological adhesives for corneal perforation treatment].

Objective: To investigate of the effectiveness of biological adhesives in corneal perforation treatment.

Method: Three types of surgical treatment of corneal perforation were performed on albino rabbits. Procedure 1 involved perforation closure using cyanoacrylate adhesive (DERMABOND), Procedure 2 involved a gelatinous glue adhesive, gelatin resorcin and formaldehyde (GRF), and Procedure 3 involved routine perforation repair using 10-0 nylon sutures.

Bronchial reversibility with a short-acting β2-agonist predicts the FEV1 response to administration of a long-acting β2-agonist with inhaled corticosteroids in patients with bronchial asthma.

A long-acting β2-agonist (LABA) combined with an inhaled corticosteroid (ICS) is frequently prescribed as initial therapy in steroid-naïve asthma patients because of its effective control of symptoms and improvement of pulmonary function. However, it is unclear which patients will be responsive to LABAs and whether bronchial responsiveness to LABAs is similar to that to short-acting β2-agonists (SABAs) in a clinical setting. Therefore, the goal of the present study was to compare the changes in spirometric parameters after SABA (salbutamol) inhalation to those after 1-month LABA/ICS (salmeterol/fluticasone propionate) therapy.

Similar changes of hypothalamic feeding-regulating peptides mRNAs and plasma leptin levels in PTHrP-, LIF-secreting tumors-induced cachectic rats and adjuvant arthritic rats.

Parathyroid hormone-related protein (PTHrP) is a causative factor of humoral hypercalcemia in malignancy. However, it is difficult to explain the mechanism of anorexia/cachexia with PTHrP secretion in detail. Previously, we demonstrated that the expressions of orexigenic peptides increased and anorexigenic peptides decreased under cachectic conditions in rats carrying tumors secreting PTHrP.

Structure-activity relationships of bioisosteric replacement of the carboxylic acid in novel androgen receptor pure antagonists.

A series of 5,5-dimethylthiohydantoin derivatives were synthesized and evaluated for androgen receptor pure antagonistic activities for the treatment of hormone refractory prostate cancer. CH4933468 (32d) with a sulfonamide side chain not only exhibited antagonistic activity with no agonistic activity in the reporter gene assay but also inhibited the growth of bicalutamide-resistant cell lines. This compound also inhibited tumor growth of the LNCaP xenograft in mice dose-dependently.

A novel nonsecosteroidal VDR agonist (CH5036249) exhibits efficacy in a spontaneous benign prostatic hyperplasia beagle model.

To date, there have been no reports showing the efficacy of nonsecosteroidal vitamin D receptor (VDR) agonists in a benign prostatic hyperplasia (BPH) animal model. To examine the efficacy of CH5036249, a novel nonsecosteroidal VDR agonist, we orally administered the compound at 0.03 microg/kg to a beagle model with spontaneous BPH.

A pleuro-peritoneal communication through the diaphragm affected with lymphangioleiomyomatosis.

A 30-year-old Japanese woman with lymphangioleiomyomatosis (LAM) developed a left chylothorax and chylous ascites. A pleuro-peritoneal communication was confirmed by a scintigram with (99)mTc-labeled macroaggregated-albumin injected into the peritoneal cavity. Video-assisted thoracic surgery revealed a protruding papillary lesion on the left diaphragm.

Structural basis for antibody discrimination between two hormones that recognize the parathyroid hormone receptor.

Parathyroid hormone-related protein (PTHrP) plays a vital role in the embryonic development of the skeleton and other tissues. When it is produced in excess by cancers it can cause hypercalcemia, and its local production by breast cancer cells has been implicated in the pathogenesis of bone metastasis formation in that disease. Antibodies have been developed that neutralize the action of PTHrP through its receptor, parathyroid hormone receptor 1, without influencing parathyroid hormone action through the same receptor.

Crystallization of the receptor-binding domain of parathyroid hormone-related protein in complex with a neutralizing monoclonal antibody Fab fragment.

Parathyroid hormone-related protein (PTHrP) plays an important role in regulating embryonic skeletal development and is abnormally regulated in the pathogenesis of skeletal complications observed with many cancers and osteoporosis. It exerts its action through binding to a G-protein-coupled seven-transmembrane cell-surface receptor (GPCR). Structurally, GPCRs are very difficult to study by X-ray crystallography.

Novel models of cancer-related anemia in mice inoculated with IL-6-producing tumor cells.

We established models of cancer-related anemia in mice from subcutaneous inoculation of two IL-6-producing cancer cell lines, human lung cancer cell line LC-06-JCK and murine colon26 clone 5 colon cancer cells. In both models, elevated levels of IL-6 were detected in sera and hemoglobin levels significantly decreased compared with non-tumor-bearing mice. In the LC-06-JCK model, serum albumin levels also decreased with elevated levels of human IL-6 in sera.

Discovery of an orally-active nonsteroidal androgen receptor pure antagonist and the structure-activity relationships of its derivatives.

The 3-(4-cyano-3-trifluoromethylphenyl)-5,5-dimethylthiohydantoin derivatives which have carboxy-terminal side chains were synthesized and their agonistic/antagonistic activities against androgen receptor (AR) measured. Among them, compound 13b showed antagonistic activity (IC50=130 nM) with no agonistic activity even at 10000 nM. This compound exhibited significant metabolic stability and oral antiandrogenic activity (ED50=7 mg/kg).

[PTHrP and cancer cachexia].

Parathyroid hormone-related peptide (PTHrP) was discovered to be a causative factor of humoral hypercalcemia of malignancy (HHM) . It also causes cachexia including reduced food intake, body weight loss, and decreased locomotor activity by a mechanism that is independent of hypercalcemia and proinflammatory cytokine actions. PTHrP-induced cachexia is not associated with the repression of orexigenic peptides or induction of anorexigenic peptides ; unexpectedly, the expression of orexigenic peptides was increased and that of anorexigenic peptides was decreased in animals that developed PTHrP-induced cachexia.

Staging of early colorectal cancers: magnifying colonoscopy versus endoscopic ultrasonography for estimation of depth of invasion.

Background And Aims: Preoperative estimation of depth of invasion in early colorectal cancers (CRCs) is essential for patient management. This study was conducted to compare the diagnostic accuracies of magnifying colonoscopy and endoscopic ultrasonography (EUS) for estimating the depth of invasion of early CRCs.

Subjects And Methods: A total of 438 early CRCs were removed endoscopically or surgically from July 1993 through March 1999 at our hospital.

Discovery and structure-activity relationships of new steroidal compounds bearing a carboxy-terminal side chain as androgen receptor pure antagonists.

Lead optimization of CH4892280 (4), an androgen receptor (AR) pure antagonist, was investigated. Compounds 6 and 7, which have a carboxylic acid at the end of the side chain at the position 7alpha of dihydrotestosterone (DHT), showed partial agonistic activities in reporter gene assay (RGA). Conversion of the steroidal core structure to 17alpha-methyltestosterone gave compound 14, which showed weak pure antagonistic activity.

Involvement of cyclooxygenase-2 in the tumor site-dependent production of parathyroid hormone-related protein in colon 26 carcinoma.

It has been shown that in the mouse colon 26 tumor model, tumors grown in the subcutis (subcutis colon 26) caused early onset of cachectic syndromes, whereas those in the liver (liver colon 26) did not. Both interleukin (IL)-6 and parathyroid hormone-related protein (PTHrP) were involved in the development of cachectic syndromes in this tumor model. However, whether expression of PTHrP and IL-6 is differently regulated in the tumor microenvironment is unclear.

Parathyroid hormone-related protein induces cachectic syndromes without directly modulating the expression of hypothalamic feeding-regulating peptides.

Purpose: Parathyroid hormone-related protein (PTHrP) is a causative factor of humoral hypercalcemia of malignancy (HHM) and concurrent anorexia and wasting. Because changes in the expression of hypothalamic feeding-regulating peptides can directly affect appetites and thereby can cause anorexia and wasting, we addressed whether the cachectic syndromes induced by PTHrP rely on the action of hypothalamic feeding-regulating peptides.

Experimental Design: Rats were inoculated with a LC-6 human cancer xenograft that secreted PTHrP, and the mRNA levels of the hypothalamic feeding-regulating peptide genes and serum leptin levels were examined before and after the development of HHM by in situ hybridization histochemistry and ELISA, respectively.

Discovery of 7alpha-substituted dihydrotestosterones as androgen receptor pure antagonists and their structure-activity relationships.

A series of 7alpha-substituted dihydrotestosterone derivatives were synthesized and evaluated for androgen receptor (AR) pure antagonistic activity. From reporter gene assay (RGA), the compound with a side chain containing N-n-butyl-N-methyl amide (19a) showed pure antagonistic activity (IC(50)=340nM, FI(5)>10,000nM), whereas known AR antagonists showed partial agonistic activities. The optimization of 19a led to compound 23 (CH4892280), which showed more potent pure antagonistic activity (IC(50)=190nM, FI(5)>10,000nM).

Capecitabine improves cancer cachexia and normalizes IL-6 and PTHrP levels in mouse cancer cachexia models.

Purpose: To clarify the potential of parathyroid hormone-related protein (PTHrP) and interleukin-6 (IL-6) as cachectic factors in a colon 26 model and the effects of capecitabine on cancer cachexia as determined by plasma levels of IL-6 and PTHrP and body weight loss.

Methods: From two colon 26 sublines-cancer cachectic clone20 and non-cachectic clone5 plasma levels of PTHrP protein and mRNA expression levels in tumor tissues were compared. An IL-6 neutralizing antibody, a PTHrP neutralizing antibody, and capecitabine were administered into mice bearing clone20 and their anticachectic effects evaluated.

Humanized monoclonal antibody against parathyroid hormone-related protein suppresses osteolytic bone metastasis of human breast cancer cells derived from MDA-MB-231.

Background: Parathyroid hormone-related protein (PTHrP) has been implicated in bone metastasis. However, the effects on bone metastasis of blocking the PTHrP function have not been tested in the clinic. Here, the effects of a humanized anti-PTHrP monoclonal antibody (mAb) on bone metastasis in a human xenograft model are shown.