Publications by authors named "Kazuhiro Nishida"

41 Publications

Perforation of intestinal leiomyosarcoma: A case report.

Int J Surg Case Rep 2021 Feb 19;79:327-330. Epub 2021 Jan 19.

Department of Surgery, Tokyo Bay Medical Center, 3-4-32 Todaijima, Urayasu, Chiba, 279-0001, Japan. Electronic address:

Introduction And Importance: The majority of gastrointestinal sarcoma is gastrointestinal stromal tumors and intestinal leiomyosarcoma is rare. Small intestinal mesenchymal tumors are often large at diagnosis, and they commonly present with bleeding or intussusception. We report a perforation associated with intestinal leiomyosarcoma.

Case Presentation: A 66-year-old man presented with severe epigastric pain. A physical examination showed tachycardia and a diffusely tender and rigid abdomen. Computed tomography showed a massive tumor and free air. A laparotomy was performed to treat lower digestive perforation. Massive tumor, which invaded surrounding intestine, was 20 cm in size at the ileum. The involved intestine was perforated. We confirmed that feeding artery was superior mesenteric artery and performed partial intestinal resection. His clinical course was uneventful and discharged 10 days postoperatively. The pathological findings showed spindle shaped and the tumor invaded the mucosa at the perforated site. Immunohistochemical spectrum resulted c-kit negative, S-100 negative, Desmin positive, alpha smooth muscle actin(αSMA) positive and Ki-67 30-40 %. The pathological findings were leiomyosarcoma.

Discussion: Gastrointestinal sarcoma is sometimes found by bleeding. In our patient, leiomyosarcoma invaded surrounding intestine, it made the intestine wall frail and caused perforation. The intestinal perforation which was involved by leiomyosarcoma has been rarely reported to the best of our knowledge since WHO refined leiomyosarcoma.

Conclusions: Although intestinal leiomyosarcoma is rare, we should know that it can involve surrounding intestines and make them perforated.
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http://dx.doi.org/10.1016/j.ijscr.2021.01.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840855PMC
February 2021

Failure of Nonoperative Management following Angioembolization for Blunt Splenic and Pancreatic Tail Injury.

Case Rep Emerg Med 2020 29;2020:8863885. Epub 2020 Oct 29.

Department of General Surgery, Tokyo Bay Medical Center, 3-4-32, Todaijima, Urayasu City Chiba 279-0001, Japan.

Background: Over several decades, standard management of blunt spleen injury (BSI) has been changed from operative intervention to the selective operative and nonoperative management (NOM). However, some patient needs laparotomy first. This article describes a case of a BSI patient who failed nonoperative management after angioembolization (AE). . A 58-year-old man fell from his motorcycle and was brought to our hospital. His vital sign was stable after extracellular fluid bolus. A contrast-enhanced computed tomography scan of the abdomen showed AAST grade V spleen injury. AE was performed for the splenic artery, but his systolic blood pressure suddenly dropped under 60 mmHg. The resuscitative endovascular balloon occlusion of the aorta was inserted, and immediate laparotomy was performed. A pancreatic tail injury was detected, and the splenic artery and vein were burst at the pancreatic tail and controlled by hemostatic suture. After splenectomy, a drain was placed at the pancreatic tail and the abdomen was temporally closed. The postoperative course was not remarkable except for abdominal abscess treated with antibiotics, and he was discharged on foot.

Conclusion: Although NOM is becoming one of the choices for severe BSI, there will still be a patient who requires surgery. Surgeons should be aware of the mechanism of injury and the limitation of AE as an adjunct to NOM. Patient selection for initial NOM and timing to convert to laparotomy are important.
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http://dx.doi.org/10.1155/2020/8863885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644325PMC
October 2020

Rupture of Hepatocellular Carcinoma after Transarterial Chemoembolization followed by Massive Gastric Bleeding.

Case Reports Hepatol 2018 4;2018:4576276. Epub 2018 Jun 4.

Department of Emergent and Critical Care Medicine, Saiseikai Yokohamashi Tobu Hospital, 3-6-1, Shimosueyoshi, Tsurumi, Yokohama-city, Kanagawa 230-8765, Japan.

Introduction: Transarterial chemoembolization (TACE) is the first-line therapy for patient with unresectable hepatocellular carcinoma (HCC). Although TACE is a generally safe procedure, major complications can be occurred. We describe a patient with rupture of HCC after TACE followed by gastric bleeding.

Case Presentation: An 81-year-old man presented with worsening epigastric pain. He had been diagnosed with multiple HCC with nonalcoholic steatohepatitis and underwent TACE 19 days previously. A contrast enhanced computed tomography (CT) scan of the abdomen showed rupture of an HCC. He was treated nonoperatively and discharged on hospital day 18. Five weeks after TACE, he was emergently admitted with massive hematochezia and shock. A contrast enhanced CT scan demonstrated extrinsic gastric compression by an HCC lesion with extravasation of contrast into the stomach. Emergent upper gastrointestinal endoscopy showed a bleeding gastric ulcer with extraluminal compression which was successfully controlled by hypertonic saline-epinephrine injection. Due to tumor progression, he was discharged for palliative care and died six weeks after TACE.

Conclusion: Rupture of HCC is a life-threatening complication after TACE with mortality rates up to 50%. After treatment of a ruptured HCC, extragastric compression and bleeding can occur due to direct compression by a primary lesion or intraperitoneal dissemination.
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http://dx.doi.org/10.1155/2018/4576276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008880PMC
June 2018

Necrotizing soft tissue infection of the thigh associated with retroperitoneal abscess in a patient with locally advanced ascending colon cancer: A case report.

IDCases 2017 9;10:112-114. Epub 2017 Sep 9.

Department of Surgery, Yokosuka General Hospital Uwamachi, 2-36 Uwamachi Yokosuka City, Kanagawa, 238-8567, Japan.

Necrotizing soft tissue infection (NSTI) is a rare but rapidly progressing soft-tissue infection. Few reports of NSTI caused by colon cancer have been published. We present a rare case of NSTI of the thigh associated the retroperitoneal spread of ascending colon cancer. A 64-year-old man had noticed right hip pain since 3 months before admission, he felt pain in the right thigh which was reddening, and he had difficulty in walking. He was referred to Yokosuka general hospital Uwamachi. Anterolateral aspect of his right thigh was reddening and swelling. The patient was diagnosed with a psoas abscess and a NSTI of the right thigh caused by penetration of ascending colon tumor. The patient underwent debridement of severely necrotized tissue in the right thigh, diverting ileostomy and subsequently a right hemicolectomy with reversal of the ileostomy were performed. He was discharged 70 days after the first surgery. Colon cancer can be a cause of retroperitoneal abscess accompanied by NSTI of the thigh. Two-stage surgery was an efficient option in this patient with NSTI of the thigh associated with locally advanced ascending colon cancer.
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http://dx.doi.org/10.1016/j.idcr.2017.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671397PMC
September 2017

Successful treatment with hyperbaric oxygen therapy for pneumatosis cystoides intestinalis as a complication of granulomatosis with polyangiitis: a case report.

J Med Case Rep 2017 Sep 17;11(1):263. Epub 2017 Sep 17.

Department of Surgery, Yokosuka General Hospital Uwamachi, 2-36 Uwamachi, Yokosuka, Kanagawa, 238-8567, Japan.

Background: Although gastrointestinal involvement in patients with granulomatosis with polyangiitis is uncommon, it is associated with mild to severe life-threatening complications. We present a case of pneumatosis cystoides intestinalis in a patient with granulomatosis with polyangiitis that was treated successfully with hyperbaric oxygen.

Case Presentation: A 70-year-old Japanese man with a 3-year history of granulomatosis with polyangiitis consulted our hospital with a complaint of severe back pain. Computed tomography showed a large amount of gas located in his bowel wall and mesentery. He underwent urgent exploratory laparotomy, which led to a diagnosis of pneumatosis cystoides intestinalis without intestinal perforation or necrosis. He consequently underwent 13 sessions of hyperbaric oxygen therapy and was discharged from our hospital without complications.

Conclusions: Several previous reports have supported the efficacy of hyperbaric oxygen for treating pneumatosis cystoides intestinalis. The present case, however, is the first in which pneumatosis cystoides intestinalis in a patient with granulomatosis with polyangiitis was successfully treated with hyperbaric oxygen. We therefore suggest that hyperbaric oxygen therapy could be a candidate treatment for pneumatosis cystoides intestinalis in patients with granulomatosis with polyangiitis.
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http://dx.doi.org/10.1186/s13256-017-1421-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602788PMC
September 2017

Toxic shock syndrome caused by suture abscess with methicillin-resistant Staphylococcus aureus (MRSA) with late onset after Caesarean section.

IDCases 2017 15;10:12-14. Epub 2017 Jul 15.

Department of Surgery, Yokosuka General Hospital Uwamachi, 2-36 Uwamachi, Yokosuka City, Kanagawa 238-8567, Japan.

Toxic shock syndrome (TSS) is a rare but life-threatening multisystem disease known to develop in the early postoperative period after various surgery. We report a rare case in which a patient who underwent Caesarean section developed TSS caused by methicillin-resistant (MRSA) on the 39th postoperative day. She was treated with debridement because of the possible diagnosis of necrotizing soft tissue infections. Culture test from the resected specimen was positive for MRSA. She was diagnosed with TSS caused by suture abscess and was treated with intensive care including antimicrobials. After a good postoperative course, she was discharged on the 30th postoperative day. TSS occurring 4 weeks after operation is extremely rare, but late-onset of suture abscess is known to occur. We should becognizant of development with TSS beyond early postoperative period.
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http://dx.doi.org/10.1016/j.idcr.2017.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536821PMC
July 2017

Laparoscopic resection of sigmoid colon cancer with intestinal malrotation: A case report.

Int J Surg Case Rep 2017 20;34:77-80. Epub 2017 Mar 20.

Department of Surgery, Yokosuka General Hospital Uwamachi, 2-36 Uwamachi, Yokosuka City, Kanagawa, 238-8567, Japan. Electronic address:

Introduction: Intestinal malrotation is a congenital abnormality which occurs due to a failure of the normal 270° rotation of the midgut. The non-rotation type is usually asymptomatic and discovered incidentally on imaging studies. Intestinal malrotation accompanied by colon cancer is extremely rare.

Presentation Of Case: A 53-year-old male presented with postprandial abdominal discomfort. Colonoscopy showed a 14mm polyp in the sigmoid colon and endoscopic polypectomy was performed. Pathological evaluation revealed an adenocarcinoma invading the submucosa more than 1000μm with positive vertical and horizontal margins. A contrast enhanced computed tomography scan showed an anatomic variant of the ileocolic and inferior mesenteric arteries originating from a common channel branching from the abdominal aorta. Laparoscopic sigmoid colon resection was performed. The patient did well post operatively.

Discussion: The usual trocar placement for laparoscopic left side colectomy was used, and we found no difficulties intraoperatively. To secure safe ligation, the divisions of the common channel branching from the abdominal aorta were exposed as in a usual D3 dissection, and the inferior mesenteric artery was ligated after confirmation of the bifurcation of the ileocolic and inferior mesenteric artery.

Conclusion: To the best of our knowledge, this is the first report of laparoscopic resection of a sigmoid colon cancer with intestinal malrotation. It was performed without difficulty using the usual trocar placement, with appropriate attention to the variant in vascular anatomy.
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http://dx.doi.org/10.1016/j.ijscr.2017.03.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5377292PMC
March 2017

Treatment of Complete Anal Stricture after Diverting Colostomy for Fournier's Gangrene.

Case Rep Surg 2017 31;2017:2062157. Epub 2017 Jan 31.

Department of Surgery, Tokyo Bay Urayasu-Ichikawa Medical Center (Noguchi Memorial Institution Hospital), Urayasu, Japan.

. Anal stenosis is a rare but serious complication of anorectal surgery. Severe anal stenosis is a challenging condition. . A 70-year-old Japanese man presented with a ten-hour history of continuous anal pain due to incarcerated hemorrhoids. He had a history of reducible internal hemorrhoids and was followed for 10 years. He had a fever and nonreducible internal hemorrhoids surrounding necrotic soft tissues. He was diagnosed as Fournier's gangrene and treated with debridement and diverting colostomy. He needed temporary continuous renal replacement therapy and was discharged on postoperative day 39. After four months, severe anal stenosis was found on physical examination, and total colonoscopy showed a complete anal stricture. The patient was brought to the operating room and underwent colostomy closure and anoplasty. He recovered without any complications. . We present a first patient with a complete anal stricture after diverting colostomy treated with anoplasty and stoma closure. This case reminds us of the assessment of distal bowel conduit and might suggest that anoplasty might be considered in the success of the colostomy closure.
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http://dx.doi.org/10.1155/2017/2062157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306967PMC
January 2017

Molecular heterogeneity in the novel fusion gene : Diversity of genomic breakpoints in gastric cancer with high-level amplifications at 11p13 and 10q26.

Oncol Lett 2017 Jan 15;13(1):215-221. Epub 2016 Nov 15.

Department of Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-8566, Japan.

Several novel fusion transcripts were identified by next-generation sequencing in gastric cancer; however, the breakpoint junctions have yet to be characterized. The present study characterized a plethora of genomic breakpoints in the SNU-16 gastric cancer cell line, which harbored homogeneously staining regions (hsrs) and double minute chromosomes. Oligonucleotide microarrays revealed high-level amplifications at chromosomes 8q24.1 (0.8 Mb region), 10q26 (1.1 Mb) and 11p13 (1.1 Mb). These amplicons contained and at chromosome 8q24.1, , and at chromosome 10q26, and 24 genes, including , , and , at chromosome 11p13. Based on these findings, reverse transcription-polymerase chain reaction (PCR) was performed using various candidate gene primers to detect possible fusion transcripts, and several products using primer sets for the and genes were detected. Eventually, three in-frame and two out-of-frame fusion transcripts were detected. Notably, PCR analysis of the entire genomic DNA detected three distinct genomic junctions. The breakpoints were within intron 5 of , which contained three distinct breakpoints, and introns 5, 7 and 9 of . Fluorescence hybridization showed several fusion signals within hsrs using two short probes (~10-kb segments of a bacterial artificial chromosome clone) containing exons 2-5 of or exons 11-13 of . Although, for any given fusion, a multiplicity of transcripts is thought to be created by alternative splicing of one rearranged allele, the results of the present study suggested that genomic fusions of and are generated in hsrs with a diversity of breakpoints that are then faithfully transcribed.
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http://dx.doi.org/10.3892/ol.2016.5386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5244987PMC
January 2017

Flare-Up Diverticulitis in the Terminal Ileum in Short Interval after Conservative Therapy: Report of a Case.

Case Rep Surg 2016 20;2016:8162797. Epub 2016 Dec 20.

Department of Surgery, Yokosuka General Hospital Uwamachi, 2-36 Uwamachi Yokosuka City, Kanagawa 238-8567, Japan.

Diverticulitis in the terminal ileum is uncommon. Past reports suggested that conservative therapy may be feasible to treat terminal ileum diverticulitis without perforation; however, there is no consensus on the therapeutic strategy for small bowel diverticulitis. We present a 37-year-old man who was referred to our hospital for sudden onset of abdominal pain and nausea. He was diagnosed with diverticulitis in the terminal ileum by computed tomography (CT). Tazobactam/piperacillin hydrate (18 g/day) was administered. The antibiotic treatment was maintained for 7 days, and the symptoms disappeared after the treatment. Thirty-eight days after antibiotic therapy, he noticed severe abdominal pain again. He was diagnosed with diverticulitis in terminal ileum which was flare-up of inflammation. He was given antibiotic therapy again. Nine days after antibiotic therapy, laparoscopy assisted right hemicolectomy and resection of 20 cm of terminal ileum were performed. Histopathology report confirmed multiple ileal diverticulitis. He was discharged from our hospital 12 days after the surgery. Colonoscopy was performed two months after the surgery and it revealed no finding suggesting inflammatory bowel disease. Surgical treatment should be taken into account as a potential treatment option to manage the diverticulitis in the terminal ileum even though it is not perforated.
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http://dx.doi.org/10.1155/2016/8162797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5206413PMC
December 2016

Ascending colon cancer associated with deposited ova of Schistosoma japonicum in non-endemic area.

IDCases 2016 20;6:52-54. Epub 2016 Sep 20.

Department of surgery, Yokosuka general hospital Uwamachi, 2-36 Uwamachi Yokosuka City, Kanagawa, 238-8567, Japan.

Some reports suggest the positive correlation between Schistosoma japonicum infection and colorectal cancer, however the sufficient evidence that supports a causal relationship between them has not been established. Japan used be an endemic area of infection for 40 years ago. But now all of Japan is a non-endemic area of infection. We report a case of ascending colon cancer associated with deposited ova of in non-endemic area.
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http://dx.doi.org/10.1016/j.idcr.2016.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048109PMC
September 2016

Edwardsiella tarda bacteremia with metastatic gastric cancer.

IDCases 2016 1;5:76-7. Epub 2016 Aug 1.

Department of Surgery, Yokosuka General Hospital Uwamachi, 2-36 Uwamachi Yokosuka City, Kanagawa, 238-8567, Japan.

Edwardsiella tarda (E. tarda) is a rare human pathogen; however, the overall mortality of bacteremia is reported to be up to 50%. Here, we describe a case of cholangitis with E. tarda bacteremia who had a pancreatoduodenectomy for a locally advanced gastric cancer. He was successfully treated using a cefmetazole, a second generation cephalosporin for 14 days. To the best of our knowledge, this is the first case report about E. tarda bacteremia after biliary reconstruction.
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http://dx.doi.org/10.1016/j.idcr.2016.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978197PMC
August 2016

Infected Abdominal Aortic Aneurysm with Helicobacter cinaedi.

Case Rep Surg 2016 17;2016:1396568. Epub 2016 Jan 17.

Department of Surgery, Jichi Medical University, Tochigi, Japan.

Helicobacter cinaedi is a rare human pathogen which has various clinical manifestations such as cellulitis, bacteremia, arthritis, meningitis, and infectious endocarditis. We report an abdominal aortic aneurysm infected with Helicobacter cinaedi, treated successfully with surgical repair and long-term antimicrobial therapy.
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http://dx.doi.org/10.1155/2016/1396568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739218PMC
February 2016

Cross-reactivity of immunoglobulin A secreted on the nasal mucosa in mice nasally inoculated with inactivated H1N1 influenza A viruses in the presence of D-octaarginine-linked polymers.

Eur J Pharm Biopharm 2015 May 23;92:56-64. Epub 2015 Feb 23.

Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. Electronic address:

We evaluated cross-reactivity of immunoglobulin A (IgA) secreted on the nasal mucosa in mice that were nasally inoculated 4 times with a mixture of inactivated H1N1 influenza A viruses and poly(N-vinylacetamide-co-acrylic acid) (PNVA-co-AA) bearing d-octaarginine at 7-day intervals. Three viral strains (A/Puerto Rico/8/34, A/New Caledonia/20/99 IVR116, and A/Solomon Islands/03/2006) and D-octaarginine-linked polymers with different molecular weights were used as antigens and their carriers, respectively. Secretion of intranasal IgA was barely observed when the inactivated virus alone was administered. The polymer induced the production of intranasal IgA specific to the inoculated viruses, irrespective of the viral strain and molecular weight of the polymer. The respective antibodies cross-reacted to recombinant hemagglutinin proteins of not only the viral strain used for immunization but also other H1N1 strains, including A/Puerto Rico/8/34 strain whose hemagglutinin proteins are diverse from those of other strains. Mice with high reactivity of IgA to the inoculated viruses tended to acquire clear cross-reactivity to other viral strains. Notably, IgA induced by inactivated H1N1 A/New Caledonia/20/99 IVR116 strain with the strongest immunogenicity between 3 antigens in the presence of the polymer cross-reacted to recombinant hemagglutinin proteins of the A/Brisbane/10/2007 and A/Viet Nam/1194/2004 strains, which are categorized into H3N2 and H5N1, respectively. Our polymer is a potential candidate for an efficient antigen carrier that induces mucosal IgA having cross-reactivity to antigenically drifted variants, irrespective of the subtype of viral strains.
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http://dx.doi.org/10.1016/j.ejpb.2015.02.010DOI Listing
May 2015

Identification of novel fusion genes with 28S ribosomal DNA in hematologic malignancies.

Int J Oncol 2014 Apr 5;44(4):1193-8. Epub 2014 Feb 5.

Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.

Fusion genes are frequently observed in hematologic malignancies and soft tissue sarcomas, and are usually associated with chromosome abnormalities. Many of these fusion genes create in-frame fusion transcripts that result in the production of fusion proteins, and some of which aid tumorigenesis. These fusion proteins are often associated with disease phenotype and clinical outcome, and act as markers for minimal residual disease and indicators of therapeutic targets. Here, we identified the 28S ribosomal DNA (RN28S1) gene as a novel fusion partner of the B-cell leukemia/lymphoma 11B gene (BCL11B), the immunoglobulin κ variable 3-20 gene (IGKV3-20) and the component of oligomeric Golgi complex 1 gene (COG1) in hematologic malignancies. The RN28S1-BCL11B fusion transcript was identified in a case with mixed-lineage (T/myeloid) acute leukemia having t(6;14)(q25;q32) by cDNA bubble PCR using BCL11B primers; however, the gene fused to BCL11B on 14q32 was not on 6q25. IGKV3-20-RN28S1 and COG1-RN28S1 fusion transcripts were identified in the Burkitt lymphoma cell line HBL-5, and the multiple myeloma cell line KMS-18. RN28S1 would not translate, and the breakpoints in partner genes of RN28S1 were within the coding exons, suggesting that disruption of fusion partners by fusion to RN28S1 is the possible mechanism of tumorigenesis. Although further analysis is needed to elucidate the mechanism(s) through which these RN28S1-related fusions play roles in tumorigenesis, our findings provide important insights into the role of rDNA function in human genomic architecture and tumorigenesis.
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http://dx.doi.org/10.3892/ijo.2014.2291DOI Listing
April 2014

The leucine twenty homeobox (LEUTX) gene, which lacks a histone acetyltransferase domain, is fused to KAT6A in therapy-related acute myeloid leukemia with t(8;19)(p11;q13).

Genes Chromosomes Cancer 2014 Apr 21;53(4):299-308. Epub 2014 Jan 21.

Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.

The monocytic leukemia zinc finger protein KAT6A (formerly MOZ) gene is recurrently rearranged by chromosomal translocations in acute myeloid leukemia (AML). KAT6A is known to be fused to several genes, all of which have histone acetyltransferase (HAT) activity and interact with a number of transcription factors as a transcriptional coactivator. The present study shows that the leucine twenty homeobox (LEUTX) gene on 19q13 is fused to the KAT6A gene on 8p11 in a therapy-related AML with t(8;19)(p11;q13) using the cDNA bubble PCR method. The fusion transcripts contained 83 nucleotides upstream of the first ATG of LEUTX and are presumed to create in-frame fusion proteins. LEUTX is known to have a homeobox domain. Expression of the LEUTX gene was only detected in placenta RNA by RT-PCR, but not in any tissues by Northern blot analysis. The putative LEUTX protein does not contain any HAT domain, and this is the first study to report that KAT6A can fuse to the homeobox gene. The current study, with identification of a new partner gene to KAT6A in a therapy-related AML, does not elucidate the mechanisms of leukemogenesis in KAT6A-related AML but describes a new gene with a different putative function.
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http://dx.doi.org/10.1002/gcc.22140DOI Listing
April 2014

Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

Jpn J Clin Oncol 2012 Nov 14;42(11):1035-42. Epub 2012 Sep 14.

*Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, and Department of Hematology, Kyoto First Red Cross Hospital, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan.

Objective: The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy.

Methods: We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients.

Results: According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group.

Conclusions: The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.
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http://dx.doi.org/10.1093/jjco/hys148DOI Listing
November 2012

Cell-penetrating peptide-linked polymers as carriers for mucosal vaccine delivery.

Mol Pharm 2012 Oct 19;9(10):2933-41. Epub 2012 Sep 19.

Faculty of Pharmaceutical Sciences, Setsunan University , 45-1 Nagaotoge-cho, Hirakata, Osaka, Japan.

We evaluated the potential of poly(N-vinylacetamide-co-acrylic acid) modified with d-octaarginine, which is a typical cell-penetrating peptide, as a carrier for mucosal vaccine delivery. Mice were nasally inoculated four times every seventh day with PBS containing ovalbumin with or without the d-octaarginine-linked polymer. The polymer enhanced the production of ovalbumin-specific immunoglobulin G (IgG) and secreted immunoglobulin A (IgA) in the serum and the nasal cavity, respectively. Ovalbumin internalized into nasal epithelial cells appeared to stimulate IgA production. Ovalbumin transferred to systemic circulation possibly enhanced IgG production. An equivalent dose of the cholera toxin B subunit (CTB), which was used as a positive control, was superior to the polymer in enhancing antibody production; however, dose escalation of the polymer overcame this disadvantage. A similar immunization profile was also observed when ovalbumin was replaced with influenza virus HA vaccines. The polymer induced a vaccine-specific immune response identical to that induced by CTB, irrespective of the antibody type, when its dose was 10 times that of CTB. Our cell-penetrating peptide-linked polymer is a potential candidate for antigen carriers that induce humoral immunity on the mucosal surface and in systemic circulation when nasally coadministered with antigens.
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http://dx.doi.org/10.1021/mp300329rDOI Listing
October 2012

Frequent PVT1 rearrangement and novel chimeric genes PVT1-NBEA and PVT1-WWOX occur in multiple myeloma with 8q24 abnormality.

Cancer Res 2012 Oct 6;72(19):4954-62. Epub 2012 Aug 6.

Department of Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.

Chromosome 8q24 rearrangements are occasionally found in multiple myeloma and are associated with tumor progression. The 8q24 rearrangements were detected by FISH in 12 of 54 patients with multiple myeloma (22.2%) and in 8 of 11 multiple myeloma cell lines (72.7%). The breakpoints of 8q24 in 10 patients with multiple myeloma and in all multiple myeloma cell lines were assigned to a 360 kb segment, which was divided into 4 regions: approximately 120 kb centromeric to MYC (5' side of MYC), the region centromerically adjacent to PVT1 (~ 170 kb region, including MYC, of 5' side of PVT1), the PVT1 region, and the telomeric region to PVT1. PVT1 rearrangements were most common and found in 7 of 12 patients (58.3%) and 5 of 8 cell lines (62.5%) with 8q24 abnormalities. A combination of spectral karyotyping (SKY), FISH, and oligonucleotide array identified several partner loci of PVT1 rearrangements, such as 4p16, 4q13, 13q13, 14q32, and 16q23-24. Two novel chimeric genes were identified: PVT1-NBEA in the AMU-MM1 cell line harboring t(8;13)(q24;q13) and PVT1-WWOX in RPMI8226 cell line harboring der(16)t(16;22)ins(16;8)(q23;q24). The PVT1-NBEA chimera in which PVT1 exon 1 was fused to NBEA exon 2 and the PVT1-WWOX in which PVT1 exon 1 was fused to WWOX exon 9 were associated with the expression of abnormal NBEA and WWOX lacking their N-terminus, respectively. These findings suggest that PVT1 rearrangements may represent a novel molecular paradigm underlying the pathology of 8q24 rearrangement-positive multiple myeloma.
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http://dx.doi.org/10.1158/0008-5472.CAN-12-0213DOI Listing
October 2012

Bcl-2 is a better therapeutic target than c-Myc, but attacking both could be a more effective treatment strategy for B-cell lymphoma with concurrent Bcl-2 and c-Myc overexpression.

Exp Hematol 2011 Aug 11;39(8):817-28.e1. Epub 2011 May 11.

Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Objective: The prognosis for diffuse large B-cell lymphomas with concomitant overexpression of c-Myc and Bcl-2 remains dismal; there is an urgent need to clarify the significance of these two oncogenes as therapeutic targets for a more effective treatment strategy.

Materials And Methods: We established two novel cell lines, KPUM-MS3 and KPUM-UH1, from two chemoresistant patients with diffuse large B-cell lymphomas with concomitant overexpression of c-Myc and Bcl-2, and investigated the significance of c-Myc and Bcl-2 as therapeutic targets.

Results: KPUM-MS3 possesses t(14;18)(q32;q21) chromosomal translocation and KPUM-UH1 bcl-2 gene amplification, both of which account for Bcl-2 overexpression. Chromosomal translocation t(8;14)(q24;q34) was found to coexist only in KPUM-UH1, overexpression of pvt-1 messenger RNA was detected only in KPUM-MS3, and reduced expression of miR-143 and miR-145 was identified in both. Working together, these abnormalities can contribute to c-Myc overexpression. Using ABT-263, an inhibitor for Bcl-2, and 10058-F4, an inhibitor for c-Myc, we found that both cell lines were more highly sensitive to cell death as a result of Bcl-2 inhibition than of c-Myc inhibition. When combined with genotoxic agents, ABT-263 exerted additive and/or synergistic cell-killing effects, while 10058-F4 showed, at most, a modest combinatory effect. Importantly, the combination of ABT-263 and 10058-F4 had a synergistic cell-killing effect on both cell lines.

Conclusions: Our data suggest that Bcl-2 is a better therapeutic target than c-Myc, but attacking both Bcl-2 and c-Myc would be an even more effective treatment strategy for diffuse large B-cell lymphomas with concurrent Bcl-2 and c-Myc overexpression.
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http://dx.doi.org/10.1016/j.exphem.2011.05.002DOI Listing
August 2011

Identification of IGHCδ-BACH2 fusion transcripts resulting from cryptic chromosomal rearrangements of 14q32 with 6q15 in aggressive B-cell lymphoma/leukemia.

Genes Chromosomes Cancer 2011 Apr 13;50(4):207-16. Epub 2011 Jan 13.

Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.

In B-cell malignancies, genes implicated in B-cell differentiation, germinal center formation, apoptosis, and cell cycle regulation are juxtaposed to immunoglobulin loci through chromosomal translocations. In this study, we identified the BTB and CNC homology 2 (BACH2) gene as a novel translocation partner of the immunoglobulin heavy chain (IGH) locus in a patient with IGH-MYC-positive, highly aggressive B-cell lymphoma/leukemia carrying der(14)t(8;14) and del(6)(q15). Fluorescence in situ hybridization analysis using an IGH/MYC probe detected an IGH-MYC fusion signal on der(14) and IGH signal on del(6). Genome copy number analysis showed a deletion in the 6q15-25 region and a centromeric breakpoint within the BACH2 gene. cDNA bubble polymerase chain reaction using BACH2 primers revealed that the first exon of Cδ was fused to the 5'-untranslated region of BACH2 exon 2. The Cδ-BACH2 fusion transcript consisted of exon 1 of Cδ and exons 2 to 9 of BACH2, encompassing the entire BACH2 coding region, and the BACH2 was highly expressed in this patient. These results indicate that Cδ-BACH2 fusion may cause constitutive activation of BACH2. Although additional screening of 47 samples of B-cell non-Hodgkin's lymphoma (B-NHL) patients and 29 cell lines derived from B-cell malignancies by double-color fluorescence in situ hybridization analysis detected a split signal with deletion of centromeric region of BACH2 only in a patient with follicular lymphoma, BACH2 was highly expressed in lymphoma cells of the patient and B-NHL cell lines with IGH-MYC translocation. These findings suggest that BACH2 plays a critical role in B-cell lymphomagenesis, especially related to IGH-MYC translocation in some way.
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http://dx.doi.org/10.1002/gcc.20845DOI Listing
April 2011

Establishment of CD5 and CD10 double-positive mature B-cell line, WILL1, showing complex 8q24 translocation involving 14q32 and 6q27.

Int J Hematol 2008 Dec 30;88(5):536-542. Epub 2008 Oct 30.

Department of Hematology/Oncology, Wakayama Medical University, Kimi-idera 811-1, Wakayama, 641-8510, Japan.

We established a novel mature B-cell line from a CD5 and CD10 double-positive diffuse large B-cell lymphoma patient, designated as WILL1. WILL1 cells were positive for CD5, CD10, CD19, and CD20. Spectral karyotype (SKY) analysis revealed chromosome 8 signals on 6q27 as well as 14q32. Fluorescence in situ hybridization (FISH) analysis suggested that a translocation break occurred outside the immunoglobulin heavy chain (IGH) gene on 14q32. Moreover, fusion signals of IGH and C-MYC probes were detected on the derivative 6 and derivative 14 chromosomes. Southern blot analysis using a C-MYC exon II fragment failed to detect rearrangement, suggesting that the 8q24 breakpoints lay far up- or downstream of the C-MYC gene. WILL1 is a useful tool to analyze the pathogenesis of CD5 and CD10 double-positive diffuse large B-cell lymphoma, and for molecular cloning of the unique translocation breakpoints of 14q32 and 8q24 and a novel gene on 6q27.
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http://dx.doi.org/10.1007/s12185-008-0189-xDOI Listing
December 2008

A complex t(1;22;11)(q44;q13;q23) translocation causing MLL-p300 fusion gene in therapy-related acute myeloid leukemia.

Eur J Haematol 2008 Dec 6;81(6):475-80. Epub 2008 Sep 6.

Department of Laboratory Medicine, Kyorin University, Mitaka, Tokyo, Japan.

The p300 protein shows a striking homology with cyclic-AMP-response-element-binding-protein binding protein (CBP) and both proteins form a family of DNA-binding transcriptional coactivators/histone acetyltransferases. The authors, herein, report a therapy-related acute myeloid leukemia with MLL-p300 fusion gene. Spectral karyotyping clarified that chromosome 11 is involved in complex t(1;22;11)(q44;q13;q23), and is fused to the chromosome 22, and direct sequencing revealed the fusion of exon 8 of MLL and exon 15 of p300 in this case. This is only the second reported case of leukemia with an MLL-p300 fusion gene, and the other case with MLL-p300 was also a therapy-related leukemia. Considering that the MLL-CBP fusion gene is also found almost exclusively in therapy-related leukemia, the association of MLL-p300 and MLL-CBP with therapy-related leukemia rather than de novo leukemia is thereby suggested.
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http://dx.doi.org/10.1111/j.1600-0609.2008.01154.xDOI Listing
December 2008

Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma.

Blood 2008 Jul 8;112(2):383-93. Epub 2008 May 8.

Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan.

Adult T-cell leukemia/lymphoma (ATLL) is caused by latent human T-lymphotropic virus-1 (HTLV-1) infection. To clarify the molecular mechanism underlying leukemogenesis after viral infection, we precisely mapped 605 chromosomal breakpoints in 61 ATLL cases by spectral karyotyping and identified frequent chromosomal breakpoints in 10p11, 14q11, and 14q32. Single nucleotide polymorphism (SNP) array-comparative genomic hybridization (CGH), genetic, and expression analyses of the genes mapped within a common breakpoint cluster region in 10p11.2 revealed that in ATLL cells, transcription factor 8 (TCF8) was frequently disrupted by several mechanisms, including mainly epigenetic dysregulation. TCF8 mutant mice frequently developed invasive CD4(+) T-cell lymphomas in the thymus or in ascitic fluid in vivo. Down-regulation of TCF8 expression in ATLL cells in vitro was associated with resistance to transforming growth factor beta1 (TGF-beta1), a well-known characteristic of ATLL cells, suggesting that escape from TGF-beta1-mediated growth inhibition is important in the pathogenesis of ATLL. These findings indicate that TCF8 has a tumor suppressor role in ATLL.
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http://dx.doi.org/10.1182/blood-2008-01-131185DOI Listing
July 2008

Chromatic-distortion compensation in splitting and focusing of femtosecond pulses by use of a pair of diffractive optical elements.

Opt Lett 2002 Jun;27(11):969-71

We propose a simple optical system to compensate for chromatic distortion that occurs during fan-out of femtosecond pulses by diffractive optics. The proposed system comprises a pair of diffractive elements, one for splitting an incoming pulse and the other for focusing the split pulses. With an appropriate separation between the elements, chromatic distortion resulting from the spectral bandwidth of a femtosecond pulse is removed, and an array of focused pulses with the same dimensions can be obtained. The theory has been verified through optical and processing experiments with 100-fs, 800-nm pulses.
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http://dx.doi.org/10.1364/ol.27.000969DOI Listing
June 2002

Immunoglobulin light chain gene translocations in non-Hodgkin's lymphoma as assessed by fluorescence in situ hybridisation.

Eur J Haematol 2008 Feb 1;80(2):143-50. Epub 2008 Jan 1.

Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

In non-Hodgkin's lymphoma (NHL), the majority of translocations involve the immunoglobulin heavy chain gene (IGH) locus, while a few involve the immunoglobulin light chain gene (IGL) locus, consisting of the kappa light chain gene (IGkappa) and the lambda light chain gene (IGlambda). Although many reports have dealt with the translocation and/or amplification of IGH in NHL, only a few have identified IGL translocations. To identify cytogenetic abnormalities and the partner chromosomes of IGL translocations in NHL, we performed dual-colour fluorescence in situ hybridisation (DC-FISH) and spectral karyotyping (SKY) in seven NHL cell lines and 40 patients with NHL. We detected IGL translocations in two cell lines and nine patients: four patients with diffuse large B-cell lymphoma, three with follicular lymphoma, one with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue and one with mantle cell lymphoma. Five distinct partners of IGlambda translocation were identified by SKY analysis: 3q27 in three patients, and 1p13, 6p25, 17p11.2 and 17q21 in one patient each. Three cases featured double translocations of IGH and IGL. These findings warrant the identification of novel genes 1p13, 6p25, 17p11.2 and 17q21.
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http://dx.doi.org/10.1111/j.1600-0609.2007.00993.xDOI Listing
February 2008

Detection of NOTCH1 mutations in adult T-cell leukemia/lymphoma and peripheral T-cell lymphoma.

Int J Hematol 2007 Apr;85(3):212-8

Department of Molecular Hematology and Oncology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.

We analyzed NOTCH1 gene mutation in 53 adults with mature T-cell leukemia/lymphoma: 21 patients with adult T-cell leukemia (ATL), 25 with T-cell non-Hodgkin's lymphoma (T-NHL), and 7 with T-cell prolymphocytic leukemia. We detected a nonsense mutation, C7249T (resulting in Q2417X, where X is a termination codon) in the PEST domain of NOTCH1 in an ATL patient and detected a 3-bp deletion (positions 7234-7236) that resulted in deletion of a proline codon at codon 2412 in the PEST domain of NOTCH1 in a patient with a T-NHL, peripheral T-cell lymphoma-unspecified (PTCL-u). We also analyzed the expression of NOTCH1 target genes (HES1, CCND1, and MYC), all of which were expressed in the sample of the PTCL-u patient with the NOTCH1 mutation, but found only MYC to be expressed in the sample from the ATL patient. These findings suggest that nonsense mutation in the PEST domain in the ATL case was associated with NOTCH1 signaling through a pathway different from that for T-cell acute lymphoblastic leukemia (T-ALL). Although NOTCH1 mutation occurs infrequently in mature T-cell leukemia/lymphoma, NOTCH1 may be involved in leukemogenesis associated with various forms of T-cell leukemia/lymphoma rather than only with T-ALL.
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http://dx.doi.org/10.1532/IJH97.06165DOI Listing
April 2007

Establishment and characterization of the new splenic marginal zone lymphoma-derived cell line UCH1 carrying a complex rearrangement involving t(8;14) and chromosome 3.

Leuk Lymphoma 2007 Apr;48(4):767-73

The First Department of Internal Medicine, Kagawa University, Kagawa, Japan.

A new cell line, designated UCH1, was established from a patient with splenic marginal zone lymphoma (SMZL). UCH1 cells feature a mature B-cell phenotype, characterized by surface IgM +, kappa+, CD5-, CD10-, CD19+ and CD20+. The BCL2 and BCL6 genes retained their germ-line configurations and overexpression of cyclin D1 was not detected. UCH1 cells carry numerical and structural aberrations in chromosome 3, but these were too complex to be analyzed with the conventional G-banding method. Spectral karyotyping (SKY) and fluorescence in situ hybridization analysis clearly demonstrated the presence of a balanced translocation between chromosomes 8 and 14 [t(8;14)(q24;q32)] in the complex aberrations involving chromosome 3. The results of Southern blot analysis supported this finding by showing rearrangement of the c-myc gene in UCH1 cells. SKY analysis also identified a translocation involving chromosome band 18q21, to which BCL2 and MALT1 genes were assigned, suggesting their implication in the development or progression of SMZL.
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http://dx.doi.org/10.1080/10428190601094768DOI Listing
April 2007