A Comparison of Visual Field and Optic Disc Appearance Depending on the Peak Intraocular Pressure in Patients with Normal-tension Glaucoma

Purpose To review the outcome of surgery for strabismus due to ethmoid sinus surgery.Cases and Methods The series comprised 13 cases, 1 of inferior rectus paresis, 1 of superior oblique paresis, 6 of medial rectus paresis, and 5 of medial rectus muscle palsy due to third nerve palsy. In the cases of paresis of the rectus muscle, resection of the rectus muscles was mainly performed. In the cases of palsy of the rectus muscle, transposition of the extraocular muscle with simultaneous recession of the lateral rectus muscle was performed. The major aim of surgery was to bring both eyes into alignment and to eliminate diplopia in the primary position.Results The mean preoperative horizontal deviation of 18.1 degrees of exotropia in the paresis cases was reduced to 1.4 degrees of exotropia after surgery. The mean preoperative vertical deviation of 3.8 degrees of hypertropia was reduced to 1.4 degrees of hypertropia postoperatively. The mean preoperative horizontal deviation of 35.6 degrees of exotropia in the palsy cases was reduced to 9.4 degrees of exotropia after surgery. The mean preoperative vertical deviation of 2.0 degrees of hypertropia was increased to 2.6 degrees of hypertropia postoperatively. Postoperatively, diplopia was absent in 11 cases with a slightly compensatory head posture.Conclusions Surgery for strabismus due to sinus surgery induces improvements in eye position and diplopia. Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc 107:425–432, 2003)     

Alteration of regional cerebral blood flow to thyrotropin-releasing hormone therapy in acute encephalitis and encephalopathy during childhood.

BACKGROUND: Thyrotropin-releasing hormone (TRH) is now used as a therapeutic agent for various neurological disorders. Animal study has shown that TRH was attributable to increased cerebral blood flow (CBF). AIMS: There have been occasional reports that TRH therapy was effective for improving symptoms of persistent disturbance of consciousness after acute encephalitis or encephalopathy during childhood. To determine whether TRH has an effect on increasing CBF to patients who have consciousness disturbance caused by acute encephalitis or encephalopathy, and to determine the optimal method of administration. METHODS: Sixteen patients aged 0.7-10.9 years (mean age, 3.2+/-3.1 years) who presented with persistent disturbance of consciousness resulting from acute encephalitis or encephalopathy and were treated with TRH. Regional CBF (rCBF) was measured by single photon emission computed tomography before and after TRH therapy. The alteration rates of rCBF were compared between the divided two groups concerning the dose levels, dosing periods, and treatment lags. RESULTS: The alteration rates of rCBF of the high dose group were higher than those of the low dose group. Differences in the dosing periods and treatment lags did not cause any significant difference of the alteration rates of rCBF. CONCLUSION: The study showed that higher alteration rates of the CBF were observed in the higher dosing group, and TRH have the potency of increasing CBF. TRH therapy would have the potential for effective treatment of persistent consciousness disturbance caused by childhood acute encephalitis or encephalopathy.     

Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer

Vascular endothelial growth factor receptor 2 (VEGFR2) is an essential factor in tumor angiogenesis and in the growth of pancreatic cancer. Immunotherapy using epitope peptide for VEGFR2 (VEGFR2‐169) that we identified previously is expected to improve the clinical outcome. Therefore, a phase I clinical trial combining of VEGFR2‐169 with gemcitabine was conducted for patients with advanced pancreatic cancer. Patients with metastatic and unresectable pancreatic cancer were eligible for the trial. Gemcitabine was administered at a dose of 1000 mg/m² on days 1, 8, and 15 in a 28‐day cycle. The VEGFR2‐169 peptide was subcutaneously injected weekly in a dose‐escalation manner (doses of 0.5, 1, and 2 mg/body, six patients/one cohort). Safety and immunological parameters were assessed. No severe adverse effect of grade 4 or higher was observed. Of the 18 patients who completed at least one course of the treatment, 15 (83%) developed immunological reactions at the injection sites. Specific cytotoxic T lymphocytes (CTL) reacting to the VEGFR2‐169 peptide were induced in 11 (61%) of the 18 patients. The disease control rate was 67%, and the median overall survival time was 8.7 months. This combination therapy for pancreatic cancer patients was tolerable at all doses. Peptide‐specific CTL could be induced by the VEGFR2‐169 peptide vaccine at a high rate, even in combination with gemcitabine. From an immunological point of view, the optimal dose for further clinical trials might be 2 mg/body or higher. This trial was registered with ClinicalTrial.gov (no. NCT 00622622). (Cancer Sci 2009)     

Dependence of the thymidylate synthase inhibition rate on the interval after the last administration of tegafur in sigmoid colon cancer patients

The thymidylate synthase (TS) inhibition rate was measured after tegafur (FT) administration (1.5 g/day, at least 10 days) in 7 sigmoid colon cancer patients. The TS inhibition rate decreased as the interval between the time of the last administration and the time of the tumor resection increased longer. This study provides basic data for considering methods of drug administration and assessment of modification, for example, by leucovorin. © 1993 Wiley-Liss, Inc.     

Diverse roles of hepatocyte growth factor activator inhibitor type 1 (HAI-1) in the growth of glioblastoma cells in vivo

Hepatocyte growth factor activator inhibitor type-1 (HAI-1) is an integral-membrane proteinase inhibitor. In this study, we examined the effects of HAI-1 on human glioblastoma cells. Two glioblastoma cell lines (YKG-1, U251) were stably transfected with expression plasmid harboring mature membrane-form or truncated secreted-form HAI-1. Culture characteristics were not altered by the expression of HAI-1, whereas in vitro invasiveness of U251 was suppressed. On the other hand, the expression of membrane-form HAI-1 resulted in significantly enhanced tumorigenicity of both cell lines in vivo. In contrast, secreted-form HAI-1 did not promote the tumorigenicity. These results suggest that HAI-1 may play complex roles in progression of glioblastoma cells, and membrane-form HAI-1 may mediate an undefined important signaling in the cells.     

Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening

Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer-promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein-coupled receptor for short-chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT-PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short-chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract. ( Cancer Sci 2009)     

CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine

Follicular lymphoma (FL) shows co‐expression of B‐cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa‐associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10^down) GI‐FL. The diagnosis of CD10^down FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10^down GI‐FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI‐FL and nodal FL when the analysis was confined to primary GI‐FL (55.2% vs 3.5%, P < 0.001). Compared to CD10⁺ GI‐FL, CD10^down GI‐FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10^down group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa‐associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10^down GI‐FL, and an identical clone was found between CD10^down follicles and CD10⁺BCL2⁺ neoplastic follicles. In the diagnosis of cases with CD10^down BCL2⁺ follicles, careful examination with molecular studies should be carried out.     

A case of primary malignant lymphoma of the duodenum successfully treated with dose escalating chemotherapy

A 65-year-old woman with diabetes mellitus was hospitalized for heart failure and anemia in August 2001, and recovered with conservative treatment. An endoscopic examination revealed an ulcerative mass located in the duodenal bulb to the 2nd portion. Abdominal CT scan demonstrated tumor involvement in the pancreas head. The diagnosis of a diffuse large B-cell lymphoma, clinical stage IIE, was made by endoscopic biopsy. Although surgical resection of the localized intestinal tumor would have been a common choice for initial treatment, polychemotherapy was selected; the patient had diabetes mellitus and preferred polychemotherapy to surgical operation. Because of bulky intestinal mass, transmural disease and sensitive histological type, standard-dose chemotherapy was considered to include a high risk of intestinal perforation. We performed dose-escalating chemotherapy: A half dose of THP-COP (pirarubicin, cyclophosphamide, vincristine) was given at the start in October 2001, 60% THP-COP as the next cycle, 80% THP-COP as the 3rd cycle and thereafter. Without serious complications of the intestine, she received a total of 6 cycles of chemotherapy and subsequent involved field radiation. There has been no evidence of recurrence of disease 14 months from the start of chemotherapy. When conditions make surgical treatment difficult, dose-escalating chemotherapy in a treatment cycle may be considered as an alternative.