Osaka Medical Center for Cancer

Ōsaka, Japan

Osaka Medical Center for Cancer

Ōsaka, Japan
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Wakasa K.,Hokkaido University | Shime H.,Hokkaido University | Shime H.,Osaka Medical Center for Cancer | Kurita-Taniguchi M.,Osaka Medical Center for Cancer | And 5 more authors.
Microbiology and Immunology | Year: 2011

The immune system has evolved mechanisms to sense not only microbes, but also necrotic cells. The pattern-recognition receptors in macrophages/dendritic cells that stimulate the acquired immune system are closely associated with danger signaling. In this study monoclonal antibodies (mAbs) that specifically interact with necrotic cells were developed. One IgG1 and two IgM mAbs were established, and they recognized a 80 kDa protein expressed in necrotic, but not live or apoptotic, cells. These mAbs, which serve as a probe for necrosis, facilitate analyses of the role of the immune complex that consists of necrotic cells and Ab and contributes to the formation of the inflammatory milieu induced by necrotic cell death. © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

Takahashi A.,Nara Medical University | Mori E.,Nara Medical University | Su X.,Nara Medical University | Nakagawa Y.,Nara Medical University | And 9 more authors.
Journal of Radiation Research | Year: 2010

Heating induces histone H2AX phosphorylation at serine 139 (γH2AX). Phosphorylated H2AX subsequently forms foci in numerous mammalian cell lines. The aim of this study was to clarify details in the mechanisms involved in the phosphorylation of H2AX after heating. The cell lines used were DNA-PKcs knockout cells, ATM knockout cells, and their parental cell lines. To elucidate mechanisms of induction of phosphorylation of H2AX after heating, ATM/ATR inhibitor (CGK733) and DNA-PK inhibitor (NU7026) were used. The intensity of γH2AX signals was assayed with flow cytometry. The thermal dose-response curve for the fluorescence intensity of γH2AX appearance in DNA-PKcs-/- cells during the heating period was similar to that observed in DNA-PKcs+/+ cells. On the other hand, the slope of thermal dose-response curve for them in ATM-/- cells was lower than that in ATM+/+ cells. Phosphorylation of H2AX after heating was suppressed by a combination of CGK733 and NU7026 in the culture medium in DNA-PKcs-/- cells, ATM-/- cells and in their parental cells. Although the phosphorylation of H2AX after heating was not suppressed by NU7026 in their parental cells, such phosphorylation was suppressed by CGK733 in their parental cells. These results indicate that ATM is the predominant protein which is active in the phosphorylation of histone H2AX after heating.

Toita T.,University of Ryukyus | Kato S.,Japan National Institute of Radiological Sciences | Niibe Y.,Kitasato University | Ohno T.,Gunma University | And 16 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To determine the efficacy of a definitive radiotherapy protocol using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study. Methods and Materials: Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size <40 mm in diameter (assessed by T2-weighted magnetic resonance imaging), and no pelvic/para-aortic lymphadenopathy. The treatment protocol consisted of whole-pelvis external beam radiotherapy (EBRT) of 20 Gy/10 fractions, pelvic EBRT with midline block of 30 Gy/15 fractions, and HDR-ICBT of 24 Gy/4 fractions (at point A). The cumulative biologically effective dose (BED) was 62 Gy 10 (α/β = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review. Results: Between September 2004 and July 2007, 60 eligible patients were enrolled. Thirty-six patients were assessed with FIGO stage Ib1; 12 patients with stage IIa; and 12 patients with stage IIb. Median tumor diameter was 28 mm (range, 6-39 mm). Median overall treatment time was 43 days. Median follow-up was 49 months (range, 7-72 months). Seven patients developed recurrences: 3 patients had pelvic recurrences (2 central, 1 nodal), and 4 patients had distant metastases. The 2-year PDPF was 96% (95% confidence interval [CI], 92%-100%). The 2-year disease-free and overall survival rates were 90% (95% CI, 82%-98%) and 95% (95% CI, 89%-100%), respectively. The 2-year late complication rates (according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer of Grade ≥1) were 18% (95% CI, 8%-28%) for large intestine/rectum, 4% (95% CI, 0%-8%) for small intestine, and 0% for bladder. No Grade ≥3 cases were observed for genitourinary/gastrointestinal late complications. Conclusions: These results suggest that definitive radiotherapy using HDR-ICBT with a low cumulative dose schedule (BED, 62 Gy 10 at point A) can provide excellent local control without severe toxicity in nonbulky (<4-cm) early-stage cervical cancer. Copyright © 2012 Elsevier Inc. Printed in the USA. All rights reserved.

Tokumaru S.,Saga University | Toita T.,University of Ryukyus | Oguchi M.,Cancer Institute Hospital | Ohno T.,Gunma University | And 16 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: To investigate pelvic insufficiency fractures (IF) after definitive pelvic radiation therapy for early-stage uterine cervical cancer, by analyzing subjects of a prospective, multi-institutional study. Materials and Methods: Between September 2004 and July 2007, 59 eligible patients were analyzed. The median age was 73 years (range, 37-84 years). The International Federation of Gynecologic Oncology and Obstetrics stages were Ib1 in 35, IIa in 12, and IIb in 12 patients. Patients were treated with the constant method, which consisted of whole-pelvic external-beam radiation therapy of 50 Gy/25 fractions and high-dose-rate intracavitary brachytherapy of 24 Gy/4 fractions without chemotherapy. After radiation therapy the patients were evaluated by both pelvic CT and pelvic MRI at 3, 6, 12, 18, and 24 months. Diagnosis of IF was made when the patients had both CT and MRI findings, neither recurrent tumor lesions nor traumatic histories. The CT findings of IF were defined as fracture lines or sclerotic linear changes in the bones, and MRI findings of IF were defined as signal intensity changes in the bones, both on T1- and T2-weighted images. Results: The median follow-up was 24 months. The 2-year pelvic IF cumulative occurrence rate was 36.9% (21 patients). Using Common Terminology Criteria for Adverse Events version 3.0, grade 1, 2, and 3 IF were seen in 12 (21%), 6 (10%), and 3 patients (5%), respectively. Sixteen patients had multiple fractures, so IF were identified at 44 sites. The pelvic IF were frequently seen at the sacroileal joints (32 sites, 72%). Nine patients complained of pain. All patients' pains were palliated by rest or non-narcotic analgesic drugs. Higher age (>70 years) and low body weight (<50 kg) were thought to be risk factors for pelvic IF (P=.007 and P=.013, Cox hazard test). Conclusions: Cervical cancer patients with higher age and low body weight may be at some risk for the development of pelvic IF after pelvic radiation therapy. © 2012 Elsevier Inc.

Kawamura M.,JR Sendai Hospital | Abe S.,JR Sendai Hospital | Oikawa K.,JR Sendai Hospital | Terai S.,JR Sendai Hospital | And 6 more authors.
Journal of Gastroenterology and Hepatology (Australia) | Year: 2011

Background and Aim: The distributions and grades of Helicobacter pylori induced gastritis are known to vary among H. pylori-associated diseases. The aim of this study was to investigate the differences in distributions of gastric micromucosal structures observed by magnifying narrow band imaging (NBI) endoscopy among patients with different H. pylori-associated diseases. Methods: Ninety-five patients with active duodenal ulcers (n=24) and diffuse-type (n=24) and intestinal-type (n=47) early gastric cancers were enrolled. The magnified NBI findings were evaluated at the lesser and greater curvatures in the upper gastric corpus and were classified according to the modified A-B classification system. Biopsy specimens were also evaluated. Results: In a total of 190 areas observed with magnifying NBI, histological grading (inflammation, activity, atrophy and intestinal metaplasia) showed significant differences among the classified micromucosal patterns (P<0.001). Types B-1 and B-2, with mild atrophic changes and few areas of intestinal metaplasia, were seen mostly in the duodenal ulcers group. Types B-3 and A-1, with moderate atrophic changes, were seen in the diffuse-type early gastric cancers at the lesser curvature. Types A-1 and A-2, with severe atrophic change and a high frequency of intestinal metaplasia, were seen in the intestinal-type early gastric cancers at the lesser curvature. The prevalence of micromucosal structures differed significantly among the three groups both at the lesser and greater curvatures (P<0.001). Conclusions: Magnifying NBI endoscopy clearly revealed detailed micromorphological differences corresponding to the histology and endoscopic findings among patients with different H. pylori-associated diseases. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Chiyonobu T.,Kyoto Prefectural University of Medicine | Inoue N.,Osaka Medical Center for Cancer | Morimoto M.,Kyoto Prefectural University of Medicine | Kinoshita T.,Institute for Microbial Diseases | And 3 more authors.
Journal of Medical Genetics | Year: 2014

Background: Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors 150 or more kinds of proteins to the human cell surface. There are at least 26 genes involved in the biosynthesis and remodelling of GPI anchored proteins (GPI-APs). Recently, inherited GPI deficiencies (IGDs) were reported which cause intellectual disability often accompanied by epilepsy, coarse facial features and multiple anomalies that vary in severity depending upon the degree of defect and/or step in the pathway of affected gene. Methods and Results: A patient born to nonconsanguineous parents developed intractable seizures with typical hypsarrhythmic pattern in electroencephalography, and was diagnosed as having West syndrome. Because the patient showed severe developmental delay with dysmorphic facial features and hyperphosphatasia, characteristics often seen in IGDs, the patient was tested for GPI deficiency. The patient had decreased surface expression of GPI-APs on blood granulocytes and was identified to be compound heterozygous for NM_178517:c.211A>C and c.499A>G mutations in PIGW by targeted sequencing. Conclusion: Here we describe the first patient with deficiency of PIGW, which is involved in the addition of the acyl-chain to inositol in an early step of GPI biosynthesis. Therefore, IGD should be considered in West syndrome and flow cytometric analysis of blood cells is effective in screening IGD.

Murakami Y.,Research Institute for Microbial Diseases | Murakami Y.,Osaka University | Inoue N.,Osaka Medical Center for Cancer | Shichishima T.,Fukushima Medical University | And 9 more authors.
British Journal of Haematology | Year: 2012

Patients with paroxysmal nocturnal haemoglobinuria (PNH) have expanded clonal cells bearing a somatic mutation in the PIGA gene. Our previous study on two PNH patients with chromosome 12 rearrangements demonstrated the involvement of HMGA2 expression in clonal expansion. The present study investigated HMGA2 expression in PNH patients without chromosomal abnormalities. The expression of short HMGA2 with latent exon was significantly high in peripheral blood cells from 18 of 24 patients. Over-expression of truncated HMGA2 in mouse bone marrow cells caused expansion in recipient mice. These results support the idea that deregulated expression of HMGA2 causes expansion of PNH cells. © 2011 Blackwell Publishing Ltd.

Fujii T.,Tokushima University | Kitamura Y.,Tokushima University | Onishi H.,Tokushima University | Shimada A.,Tokushima University | And 3 more authors.
Practica Oto-Rhino-Laryngologica | Year: 2015

Metastatic hepatocellular carcinoma in the sinonasal region is rare. We report the case of an 85-yearold man who presented to us with a history of recurrent nasal bleeding. A reddish and hemorrhagic tumor was found in the right nasal septum. Histopathological examination of a biopsy specimen of the tumor revealed metastatic hepatocellular carcinoma. The patient had been diagnosed as having hepatocellular carcinoma many years ago and received multiple sessions of transcatheter arterial chemoembolization. Computed tomography and magnetic resonance imaging showed a slightly enhancing soft-tissue mass measuring 10 mm in diameter in the right nasal septum. We resected the metastatic hepatocellular carcinoma in the right nasal septum by endoscopic surgery under local anesthesia to control the recurrent nasal bleeding, and this treatment improved the quality of life of the patient. The postoperative course was uneventful, and until now, eight months since the surgery, the patient has shown no evidence of recurrence.

Sawahata R.,Hokkaido University | Shime H.,Hokkaido University | Yamazaki S.,Hokkaido University | Inoue N.,Osaka Medical Center for Cancer | And 5 more authors.
Microbes and Infection | Year: 2011

Macrophage-activating lipopeptide 2 (MALP-2), a mycoplasmal diacylated lipopeptide with palmitic acid moiety (Pam2), activates Toll-like receptor (TLR) 2 to induce inflammatory cytokines. TLR2 is known to mature myeloid dendritic cells (mDC) to drive mDC contact-mediated natural killer (NK) cell activation. Here we tested if MALP-2 activates NK cells through stimulation of TLR2 on mDC. Although synthetic MALP-2 with 6 or 14 amino acids (a.a.) stretch (designated as s and f) matured mDC to induce IL-6, IL-12p40 and TNF-α to a similar extent, they far less activated NK cells than Pam2CSK4, a positive control of 6 a.a.-containing diacyl lipopeptide. MALP-2s and f were TLR2/6 agonists and activate the MyD88 pathway similar to Pam2CSK4, but MALP-2s having the CGNNDE sequence acted on mDC TLR2 to barely induce external NK activation. Even the s form, with slightly high induction of IL-6 compared to the f form, barely induced in vivo growth retardation of NK-sensitive implant tumor. Pam2CSK4 and MALP-2 have the common lipid moiety but different peptides, which are crucial for NK cell activation. The results infer that MALP-2 is applicable to a cytokine inducer but not to an adjuvant for antitumor NK immunotherapy. © 2010 Institut Pasteur.

PubMed | Osaka Medical Center for Cancer &
Type: Journal Article | Journal: Radiology | Year: 2010

To prospectively determine whether slight dilatation of the main pancreatic duct and pancreatic cysts detected at ultrasonography (US) are predictive signs of pancreatic cancer.The research protocol was approved by the institutional review board, and written informed consent was obtained from all participants. One thousand fifty-eight subjects (age range, 36-80 years; mean, 61.8 years) with various kinds of abnormal US findings in the pancreas were enrolled from 1999 to 2002, after exclusion of pancreatic neoplasm and other malignant diseases. The endpoint was the subsequent development of pancreatic cancer, and the outcome was determined at the end of December 2007. To identify independent predictive variables for the subsequent development of pancreatic cancer, various baseline characteristics were examined by using a Cox regression model and a Cox proportional hazards model. The cumulative incidence of pancreatic cancer was estimated by using the Kaplan-Meyer method.During the mean follow-up of 75.5 months (+/- 17.3[standard deviation]), pancreatic cancer subsequently developed in 12 of 1058 subjects. The risk of pancreatic cancer was significantly elevated in subjects with slight dilatation (> or = 2.5 mm) of the main pancreatic duct or presence of cyst (s) (> or = 5 mm). The respective hazard ratios were 6.38 (P = .018) and 6.23 (P = .003). For subjects with both findings, the 5-year cumulative risk of pancreatic cancer was 5.62% (95% confidence interval: .37%, 13.03%), and the age-and sex-adjusted hazard ratio compared with the risk in the absence of these findings was 27.50 (P = .002).Main pancreatic duct dilatation (> or = 2.5 mm) and presence of a pancreatic cyst (> or = 5 mm) were both strong independent predictors of the subsequent development of pancreatic cancer. (c) RSNA, 2010.

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