Overexpression of glucose transporter 1 in esophageal squamous cell carcinomas: a marker for poor prognosis.

SUMMARY: Recently, Glut1 (human erythrocyte glucose transporter) expression has been demonstrated in various tumors. The aim of this study is to evaluate the prognostic utility of Glut1 expression in esophageal carcinomas. We studied Glut1 expression by immunohistochemistry of paraffin sections from 63 esophageal squamous cell carcinomas. All 63 carcinomas expressed Glut1. The mean percentage of positively stained tumor cells was 77.8% (median, 84.7%). There were two staining patterns in positive cells: 'strongly positive' and 'weakly positive'. The percentage of 'strongly positive' cells (%Glut1-SP) ranged from 0% to 95.6% (mean, 32.3%; median, 27.4%). The 5-year survival rate for patients with a high %Glut1-SP (> 30%) was significantly lower than that for patients with a low %Glut1-SP (< 30%) (P < 0.01). Statistical analysis revealed that the relative risk of death for patients with high %Glut1-SP was 2.02 times that for patients with low %Glut1-SP (P = 0.064), suggesting a possible independent predictive value for %Glut1-SP.

Effects of a new antiallergic drug, VUF-K-8788, on infiltration of lung parenchyma by eosinophils in guinea pigs and eosinophil-adhesion to human umbilical vein endothelial cells (HUVEC).

Airway inflammation and reversible airway obstruction are hallmarks of bronchial asthma. In this study, we investigated the effects of a new antiallergic drug, 7-[3-[4-(2-quinolinylmethyl)-1-piperazinyl]-propoxy]-2,3-dihydro-4H-1,4-benzothiazin-3-one (VUF-K-8788), on histopathological changes in lung parenchyma of guinea pigs during late-phase asthmatic reaction (LAR), and on eosinophil-adhesion to human umbilical vein endothelial cells (HUVEC). Repeated exposure to ovalbumin of sensitized guinea pigs induced inflammatory phenomena such as hyperplasia of airway epithelial cells, perivascular edema and infiltration of lung parenchyma by eosinophils. VUF-K-8788 inhibited these histopathological phenomena at 10 mg/kg p.o. Moreover, the eosinophil-adherence to HUVEC was inhibited by VUF-K-8788 at the concentration of 10-30 microM. In conclusion, this inhibitory effect of VUF-K-8788 on eosinophil-adherence might contribute to the prevention of LAR and infiltration by eosinophils in the experimental asthmatic model in guinea pigs.

Combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin for metastatic urothelial cancer.

PURPOSE: To investigate the activity of combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin in patients with metastatic urothelial cancer. METHODS: A group of 29 patients were treated with 2000 mg/m2 ifosfamide, 750 mg/m2 5-fluorouracil, 100 mg/m2 etoposide and 20 mg/m2 cisplatin. All four drugs were given intravenously on days 1 through 3 and the treatment was repeated every 3 weeks. Of the 29 patients, 14 had lymph node metastasis alone, and 15 had visceral lesions. RESULTS: An objective response was achieved in 17 patients (59%). There was no difference in response rates according to metastatic site including osseous lesions, which responded well in four of six patients. The 3-year survival rate for all patients was 16% with four patients who had undergone salvage surgery being alive with no evidence of disease 15 to 61 months after initiation of the treatment. A good performance status, lymph node metastasis alone and administration of chemotherapy at the full dosage had a significantly favorable impact on patient survival. Bone marrow toxicity was significant and one patient died of treatment-related sepsis. CONCLUSIONS: Ifosfamide, 5-fluorouracil, etoposide and cisplatin combination chemotherapy appeared to be active in the treatment of metastatic urothelial cancer. Although bone marrow toxicity was significant, the treatment was well tolerated by the majority of the patients. Further study may be warranted.

VUF-K-8788, a periphery-selective histamine H1 antagonist with anti-pruritic activities.

The pharmacological properties of 7-[3-[4-(2-quinolinylmethyl)-1-piperazinyl]-propoxy]-2,3-dihydro-4H-1,4-benzothiazin-3-one (VUF-K-8788) were investigated in vitro and in vivo. VUF-K-8788 inhibited [3H]-mepyramine from binding to the cell membrane of lung parenchyma (Ki value: 5.0 nM) and the histamine-induced contraction of isolated guinea pig ileum (pA2: 9.71) without affecting ileal contractions induced by acetylcholine, serotonin, KCl and BaCl2. The increase of vascular permeabilities induced by histamine and passive cutaneous anaphylaxis (PCA) in guinea pigs were inhibited by VUF-K-8788 in a dose-dependent fashion (ED50: 0.24 and 0.26 mg/kg, p.o., respectively). Moreover, the anti-histaminic effect of VUF-K-8788 was also observed in rats. In experiments on the effects on the central nervous system, VUF-K-8788 at 1 mg/kg, p.o. hardly antagonized the H1 receptor at all in the cerebral cortex of guinea pigs. VUF-K-8788 inhibited the PCA-induced scratching behavior completely without affecting thiopental-induced sleep in mice. These results suggested that VUF-K-8788 would be useful in the treatment of allergic disorders such as atopic dermatitis and eczema.

Functional disomy for Xq26.3-qter in a boy with an unbalanced t(X;21)(q26.3;p11.2) translocation.

A nine-month-old boy, with functional disomy for Xq26-qter and multiple congenital abnormalities, is reported. The boy had severe pre- and postnatal growth retardation, profound developmental delay, hypotonia, microcephaly, agenesis of the corpus callosum, dysmorphic facial features, cryptorchidism, and left multidysplastic kidney. He developed feeding difficulties and infantile spasms. G-banding analysis of his chromosomes showed additional material on the short arm of chromosome 21. His parents refused to submit to chromosome analysis. Analysis with chromosome microdissection followed by reverse and forward chromosome painting indicated his karyotype as 46,XY,der(21)t(X;21)(q26;p11.2). This is the first description of pure functional disomy for Xq26-qter due to an unbalanced X-autosome translocation.

Craniofacial and dental characteristics of Kabuki syndrome.

We describe oral manifestations in six patients (three females and three males aged 6 to 24 years) with Kabuki syndrome (KS), based on their physical, orthopantomographic, and cephalometric findings. All six patients had a high-arched palate, malocclusion, most commonly unilateral posterior cross-bite (5/6), severe maxillary recession and mid-facial hypoplasia. Other frequently observed oral manifestations included small dental arch and hypodontia. Three patients lacked permanent teeth, mostly the central/lateral incisors. Both tooth size (in primary and permanent teeth) and dental arch (in length and width) tended to be small. We would like to stress that oral care and management is a must for the well-being of KS patients.

Molecular cytogenetic analysis of eight inversion duplications of human chromosome 13q that each contain a neocentromere.

Neocentromeres are fully functional centromeres that have arisen in previously noncentromeric chromosomal locations on rearranged chromosomes. The formation of neocentromeres results in the mitotic stability of chromosomal fragments that do not contain endogenous centromeres and that would normally be lost. Here we describe a unique collection of eight independent patient-derived cell lines, each of which contains a neocentromere on a supernumerary inversion duplication of a portion of human chromosome 13q. Findings in these patients reveal insight into the clinical manifestations associated with polysomy for portions of chromosome 13q. The results of FISH and immunofluorescent analysis of the neocentromeres in these chromosomes confirm the lack of alpha-satellite DNA and the presence of CENtromere proteins (CENP)-C, -E, and hMAD2. The positions of the inversion breakpoints in these chromosomes have been placed onto the physical map of chromosome 13, by means of FISH mapping with cosmid probes. These cell lines define, within chromosome 13q, at least three distinct locations where neocentromeres have formed, with five independent neocentromeres in band 13q32, two in band 13q21, and one in band 13q31. The results of examination of the set of 40 neocentromere-containing chromosomes that have thus far been described, including the 8 neocentromere-containing chromosomes from chromosome 13q that are described in the present study, suggest that chromosome 13q has an increased propensity for neocentromere formation, relative to some other human chromosomes. These neocentromeres will provide the means for testing hypotheses about sequence requirements for human centromere formation.