Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1).

BACKGROUND: S-1, an oral fluoropyrimidine, plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. To date, no studies have evaluated the efficacy and safety of trastuzumab combined with SP in patients with human epidermal growth factor receptor type 2 (HER2)-positive AGC. METHODS: Patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, cisplatin (60 mg m(-2)) intravenously on day 1, and trastuzumab (course 1, 8 mg kg(-1); course 2 onward, 6 mg kg(-1)) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary end points included overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), and adverse events. RESULTS: A total of 56 patients were enrolled. In the full analysis set of 53 patients, the confirmed RR was 68% (95% confidence interval (CI)=54-80%), and the disease control rate was 94% (95% CI=84-99%). Median OS, PFS, and TTF were estimated as 16.0, 7.8, and 5.7 months, respectively. Major grade 3 or 4 adverse events included neutropaenia (36%), anorexia (23%), and anaemia (15%). CONCLUSIONS: Trastuzumab in combination with SP showed promising antitumour activity and manageable toxic effects in patients with HER2-positive AGC.

Validating a Markov model of treatment for hepatitis C virus-related hepatocellular carcinoma.

OBJECTIVE: We created and validated a Markov model to simulate the prognosis with treatment for HCV-related hepatocellular carcinoma (HCC) for assessment of cost-effectiveness for alternative treatments of HCC. METHOD: Markov state incorporated into the model consisted of the treatment as a surrogate for HCC stage and underlying liver function. Retrospective data of 793 patients from three university hospitals were used to determine Kaplan-Meier survival curves for each treatment and transition probabilities were derived from them. RESULTS: There was substantial overlap in the 95% CIs of the Markov model predicted and the Kaplan-Meier survival curves for each therapy. The predicted survival curves were also similar with those from the nationwide survey data supporting the external validity of our model. CONCLUSIONS: Our Markov model estimates for prognosis with HCC have both internal and external validity and should be considered applicable for estimating cost-effectiveness related to HCC.

Low energy excitation and scaling in Bi(2)Sr(2)Ca(n-1)Cu(n)O(2n+4) (n=1-3): angle-resolved photoemission spectroscopy.

Angle-resolved photoemission spectroscopy (ARPES) has been performed on the single- to triple-layered Bi-family high-T (c) superconductors (Bi(2)Sr(2)Ca(n-1)Cu(n)O(2n+4), n=1-3). We found a sharp coherent peak as well as a pseudogap at the Fermi level in the triple-layered compound. Comparison among three compounds has revealed a universal rule that the characteristic energies of superconducting and pseudogap behaviors are scaled with the maximum T (c).

Fat adherence syndrome after retinal surgery treated with amniotic membrane transplantation.

PURPOSE: We present favorable results with amniotic membrane transplantation in a patient who developed fat adherence syndrome after retinal surgery. DESIGN: Interventional case report. METHODS: A 37-year-old man had diplopia resulting from hypotropia of the left eye after retinal detachment surgery. Removal of a previously implanted silicon sponge had little effect because of fibrous adhesion between the inferior rectus muscle and adjacent periorbital fat. We performed amniotic membrane transplantation combined with conventional extraocular muscle surgery. RESULTS: Postoperatively, supraduction of the left eye became almost full. The field of binocular vision was extended markedly by treatment, both in the primary position and with downward gaze. These improvements remained stable over 1 year of follow-up. CONCLUSION: Amniotic membrane transplantation appears to be effective for preventing regrowth of restrictive scar tissue in the fat adherence syndrome.

PAX6 expression in the developing human eye.

AIMS: To investigate the changes in PAX6 expression in the developing human eye. METHODS: Six developing human eyes from 6 to 22 weeks' gestation were evaluated. Frozen sections were immunohistochemically stained with monoclonal antibody to chick Pax6 (amino acids 1-223). To verify antibody specificity, western blot analysis was carried out using cell lysates from P19 cells transfected with the human PAX6 gene. RESULTS: Western blot analysis demonstrated that the antibody reacted to human PAX6 protein. Positive immunostainings for PAX6 were seen in the surface ectoderm, lens vesicle, inner and outer layers of the optic cup, and optic stalk at 6 weeks, and in the corneal epithelia and conjunctiva, lens, and non-pigmented ciliary epithelia from 8 to 22 weeks. In the retina, positive cells were seen in the entire retina from 8 to 10 weeks, and were restricted to the ganglion cell layer and the inner and outer portions of the inner nuclear layer after 21 weeks. CONCLUSIONS: PAX6 is expressed on the surface and neuroectoderms at an early stage, then in the differentiating cells in the cornea, lens, ciliary body, and retina through development. PAX6 may play a role in determining cell fate in the morphogenesis of various human ocular tissue.

Japanese juvenile retinoschisis is caused by mutations of the XLRS1 gene.

We investigated the XLRS1 gene in Japanese patients with retinoschisis (RS). All exons of the XLRS1 gene were sequenced in 14 males, including a pair of monozygotic twins, from 11 individual families with RS and five of their mothers who are asymptomatic but diagnosed as carriers. Six kinds of missense mutations and a nonsense mutation, including six novel mutations, were detected in all 14 patients and carriers. Mutations in the XLRS1 gene are also responsible for RS in non-Caucasian patients. Most Japanese RS cases are caused by an XLRS1 gene defect. A novel mutation, Glu72Lys, was found in four families, suggesting a common mutation in the Japanese population. Clinical features of RS patients with both the Glu72Lys and Pro193Leu mutations indicate that a genotype-phenotype correlation is not recognized in RS.

Expression of the alpha1-alpha6 collagen IV chains in the dermoepidermal junction during human foetal skin development: temporal and spatial expression of the alpha4 collagen IV chain in an early stage of development.

To study the expression of the alpha1-alpha6 chains of type IV collagen in the dermoepidermal junction (DEJ) during human foetal skin development, human foetal (10 and 20 weeks of gestation) and adult skin was immunostained with specific monoclonal antibodies to the alpha1-alpha6 chains of type IV collagen. Intense expression of the alpha4 chain and weak expression of the alpha2 and alpha6 chains were observed in the DEJ of 10 weeks gestational skin. In contrast, the alpha1, alpha2, alpha5 and alpha6 chains were detected in the DEJ of 20 weeks gestational and adult skin. Preferential expression of alpha4 during the early phase of development (10 weeks of gestation) may suggest a chain-specific regulatory mechanism for type IV collagen expression and its potential role in DEJ formation during development.

CD44 expression in the developing human retina.

BACKGROUND: CD44, the transmembrane adhesion molecule, is expressed in the fetal brain and supposed to mediate neuroglial, interactions. We evaluated the expression and distribution of CD44 in the developing human retina. METHODS: Four developing human eyes were evaluated at 6, 10, 16, and 21 weeks of gestation, as well as the eyes of one infant and four adults. Frozen sections were immunohistochemically stained with monoclonal antibodies to three human CD44 clones (BU52, F10-44-2, and DF1485) and to vimentin, and antiserum to glial fibrillary acidic protein (GFAP). Specimens were evaluated by light and electron microscopy. RESULTS: Positive immunostaining for CD44 was first detected at 21 weeks of gestation in the longitudinal fibers that extended from the inner to the outer limiting membrane and around capillary vessels with the simultaneous expression of vimentin and GFAP. Immunoelectron microscopy demonstrated the presence of CD44 on the surface of Müller cells and astrocytes. CD44 was faintly seen in the Müller cells in the periphery and definitely present in the astrocytes in the infant and adult retinas. CONCLUSION: CD44 was expressed in Müller cells at a late stage of fetal development and in the fetal, infant, and adult astrocytes, which suggests that it is important in the morphogenesis and homeostasis of the neural retina.

[A morphological study on extension of extraretinal vasoproliferation in retinopathy of prematurity].

The relation between extension of extraretinal vasoproliferation and vitreous fibers in stage 3 mild retinopathy of promaturity was evaluated by light and electron microscopy using 4 eyes obtained after autopsies. Seven developing human eyes from 20 to 40 weeks' gestation were used as controls. At an early stage, when vascular tissues broke the inner limiting membrane of the retina and grew into the vitreous cavity, they extended vertically from the retina. Proliferating extraretinal vessels extended towards the posterior surface of the lens. They ran side by side with the framework of vitreous fibers. Electron microscopy demonstrated multiple attachments between vascular endothelia and vitreous fibers. Normal developing vitreous fibers were very dense and homogeneous, running towards the lens not only from the vitreous base but also from the retina at the equator and at the posterior pole. These findings suggest that extension of extraretinal vasoproliferation in retinopathy of prematurity is induced by the framework of the developing vitreous.