Skp2 overexpression is a p27Kip1-independent predictor of poor prognosis in patients with biliary tract cancers

To better understand the pathogenesis of biliary tract carcinoma (BTC) and to increase the accuracy of predicting outcomes for patients with this disease, we performed molecular cytogenetic analyses of BTC cell lines and tumors to identify non-random amplification(s) and target gene(s) within the amplicons. Among several non random chromosomal aberrations detected in BTC cell lines by comparative genomic hybridization, gain/ampli-fication of DNA at 5p was the most frequently observed alteration. We assessed the copy number and expression status of the possible target gene SKP2 for 5p amplification in cell lines and 33 primary stage II or III tumors of BTC. SKP2 was amplified, and subsequently overexpressed in both cell lines and primary tumors of BTC. However, levels of Skp2 and p27Kip1 proteins were not correlated inversely. Heightened expression of Skp2 and reduced expression of p27Kip1 were both associated with a shorter disease-free and/or overall survival in univariate analyses. In multivariate regression analyses, Skp2 and p27Kip1 were independent predictive factors. Those results suggest that (a) overexpression of Skp2 through an amplification mechanism may contribute to the progression of BTC, (b) not only each molecule, but also the combination of Skp2 and p27Kip1, might be a useful predictor of the prognosis of BTC, and (c) molecular targets of Skp2 other than p27Kip1 may also be important factors in the pathogenesis of this disease.     

A living case of pulmonary ossification associated with osteoclast formation from alveolar macrophage in the presence of T-cell cytokines

A 61-year-old woman had been coughing up blood-tinged sputum since May 1998. Chest radiography and computed tomography (CT) scans revealed a solitary mass (3 cm in greatest dimension) in the right lower field, accompanied by a surrounding area of ground glass and reticular appearance. Surgical lung biopsy was performed to the surrounding area. The pathological diagnosis was pulmonary ossification of the dendriform type. Alveolar macrophages obtained from her lung differentiated into tartrate-resistant acid phosphatase (TRAP)-positive multinucleated giant cells (MGCs) in the presence of autologous T cells or of macrophage colony stimulating factor (M-CSF) and interleukin-4 (IL-4). This results suggest the possibility that monocytes/macrophages may have the ability to form osteoclasts in the presence of cytokines that may be involved in the development of pulmonary ossification.     

Improvement in jaw motion following treatment of unilateral crossbite in a child with primary dentition: a case report

This case report examines jaw motion during both habitual opening-closing and gum chewing in a young (3 years, 10 months) patient with unilateral crossbite at the primary dentition stage. Jaw motion was measured three times: 1. before treatment; 2. after active treatment; and 3. after retention. The abnormal habitual open-close pathway seen prior to treatment was improved after retention. Prior to treatment, movement of the affected-side condyle preceded movement of the non-affected-side condyle during opening. After retention, the movement of the condyles was better coordinated. The chopping type chewing pattern, with less lateral movement, before treatment changed to a more grinding type pattern on the affected side after activation. This study suggests that the prescribed treatment effectively improved both the patient's morphology and function. However, neither the open-close pathways nor the chewing patterns were completely normal after retention. The results in this case suggest that early treatment of functional unilateral crossbite can be effective.     

Clinical efficacy of bisphosphonate therapy for bone metastasis from breast cancer

Bisphosphonates inhibit osteoclastic bone resorption and are being used as treatment for bone metastases from breast cancer. Intravenous bisphosphonate therapy can significantly reduce skeletal related events (SREs) when administered concurrently with chemotherapy or endocrine therapy. In addition, intravenous bisphosphonate monotherapy is also able to alleviate cancer induced bone pain, and to improve bone metastases in some patients. Oral bisphosphonates are not routinely used for the treatment of bone metastases due to their low bioavailability. However, minodronate, a bisphosphonate 100-fold more potent than pamidronate, is now in phase II clinical studies in Japan, and may alter the role of oral bisphosphonates in the treatment of bone metastasis from breast cancer. The ASCO guidelines recommend that patients with osteolytic bone metastases be treated not with bisphosphonate monotherapy, but with concurrent bisphosphonate and systemic therapy. In addition, it is also recommended that current standards of care for cancer pain, analgesics and radiotherapy, should not be replaced with bisphosphonate therapy.     

A case of advanced ovarian clear cell adenocarcinoma responding to cisplatin-cyclophosphamide and paclitaxel-carboplatin]

We report a case of stage IV ovarian clear cell adenocarcinoma successfully controlled by a combination of cisplatin-cyclophosphamide (CP) and paclitaxel-carboplatin (TJ). A 64-year-old female with advanced ovarian cancer and pleural effusion underwent 4 courses of combination chemotherapy with CP. The giant ovarian tumor showed a relative reduction in size and the pleural effusion disappeared. Serum CA-125 levels and CA 19-9 levels markedly decreased. Thus, the patient underwent a total hysterectomy and bilateral salphingoophorectomy. During the operation, a giant ovarian clear cell adenocarcinoma was found, but there was no peritoneal dissemination and no cancer cells in her peritoneal fluid. Thereafter, she underwent 3 courses of combination chemotherapy with TJ. She has had 13 months of stable, tumor-free survival since the operation and normal serum CA-125 and CA 19-9 levels. Ovarian clear cell adenocarcinoma generally responds poorly to cisplatin and carboplatin, but in combination chemotherapy with paclitaxel-carboplatin these may be effective.     

Technique of ultrasonic detection and mapping of abdominal wall adhesions

Summary A technique for noninvasive ultrasound examination to detect and map abdominal wall adhesions is described. The examination is based on the demonstration of movement of abdominal viscera during real-time imaging. This movement is called viscera slide and either occurs spontaneously as a result of respiratory movement or may be induced by manual compression. Abdominal wall adhesions produce a restriction of viscera slide. Ultrasonic demonstration of restricted viscera slide has been used for the precise localization and mapping of abdominal wall adhesions prior to abdominal surgery. The technique may be particularly useful in providing safe initial access in patients undergoing laparoscopy who are at increased risk for trocar injury of viscera due to abdominal wall adhesions resulting from previous surgery or peritonitis.     

Cytoplasmic calcium ion elevating factor(s) in spontaneously hypertensive rat serum

We have attempted to characterize the as yet unspecified circulating factor(s) in spontaneously hypertensive rat (SHR) serum that elevate(s) the cytoplasmic calcium ion concentration in vascular smooth muscle cells (VSMC). We measured the cytoplasmic calcium ion concentration in cultured VSMC before and after incubation with serum from SHR or Wistar-Kyoto rats (WKY). Incubation with serum from overtly hypertensive 8-week-old SHR, but not with serum from 8-week-old WKY, significantly elevated the cytoplasmic calcium ion concentration in VSMC from 8-week-old WKY and 4-week-old SHR in a dose- and an incubation period-dependent manner, although no significant elevation occurred in VSMC from 4-week-old WKY. Neither the heat-immobilized nor the trypsinized 8-week-old SHR serum elevated the cytoplasmic calcium ion concentration. Ultrafiltration procedures indicated that the molecular weight of the factor should be 10,000-30,000 daltons. Incubation with serum from 4-week-old SHR or WKY did not elevate the cytoplasmic calcium ion concentration. These results strongly suggest that: (1) a cytoplasmic calcium ion concentration elevating factor exists in serum from 8-week-old SHR but not from 4-week-old SHR, or 4- or 8-week-old WKY; (2) this factor should be of a protein nature, with a molecular weight of 10,000-30,000 daltons; (3) responsiveness to the factor appears in VSMC at a younger age in SHR than in WKY; (4) the factor elevates the cytoplasmic calcium ion concentration to the level determined a priori not by the strain but by the age of the rats from which the VSMC originate; and (5) the a priori determined level increases with the age of the rats.