35 results on '"Nobuhiro Haruki"'
Search Results
2. Data from Thioredoxin-1 Modulates Transcription of Cyclooxygenase-2 via Hypoxia-Inducible Factor-1α in Non–Small Cell Lung Cancer
- Author
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David P. Carbone, David H. Johnson, Jason D. Morrow, Sorena Nadaf, Nobuhiro Haruki, Kiyoshi Yanagisawa, and Ildiko Csiki
- Abstract
Hypoxic induction of gene expression occurs mainly via the hypoxia-inducible factor-1 (HIF-1) transcription factor and is a critical step in tumor growth. Cyclooxygenase-2 (COX-2) is commonly overexpressed in non–small cell lung cancer (NSCLC). In this study, we sought to determine the role of HIF-1 in the induction of COX-2 expression during hypoxia. Through sequence comparison of hypoxia-responsive genes, COX-2 promoter deletion analysis, and site-directed mutagenesis, we identified a hypoxia-responsive element within the COX-2 promoter that interacts with HIF-1α and underlies the mechanism of hypoxic activation of COX-2 in lung cancer cells. Proteomic analysis of NSCLC identified thioredoxin-1 as a redox protein overexpressed in NSCLC correlated with poor prognosis. We also show that thioredoxin-1 stabilizes HIF-1α to induce hypoxia-responsive genes under normoxic conditions. Our results identify two new mechanisms for regulation of COX-2 expression in NSCLC. (Cancer Res 2006; 66(1): 143-50)
- Published
- 2023
3. Supplementary Figures 1-3 from Thioredoxin-1 Modulates Transcription of Cyclooxygenase-2 via Hypoxia-Inducible Factor-1α in Non–Small Cell Lung Cancer
- Author
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David P. Carbone, David H. Johnson, Jason D. Morrow, Sorena Nadaf, Nobuhiro Haruki, Kiyoshi Yanagisawa, and Ildiko Csiki
- Abstract
Supplementary Figures 1-3 from Thioredoxin-1 Modulates Transcription of Cyclooxygenase-2 via Hypoxia-Inducible Factor-1α in Non–Small Cell Lung Cancer
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- 2023
4. A Case of Mucosal Prolapse Performed by Delorme Procedure after Laparoscopic Intersphincteric Resection
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Tomokatsu Kato, Koshiro Harata, Koji Mizoguchi, Nobuhiro Haruki, Yuki Denda, and Kohei Fujita
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medicine.medical_specialty ,business.industry ,medicine ,business ,Intersphincteric resection ,Mucosal prolapse ,Surgery - Published
- 2019
5. [Neutrophil-Lymphocyte Ratio as a Prognostic Indicator in Patients Treated with Nivolumab for Gastric Cancer]
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Kohei, Fujita, Nobuhiro, Haruki, Hiroki, Kurehara, Nobuo, Ochi, Yushi, Yamakawa, Shinnosuke, Harata, Chisa, Tsumoto, Takuma, Tsuji, Tsuyoshi, Ito, Ayaka, Izumi, Rena, Usui, and Noriyuki, Shinoda
- Subjects
Aged, 80 and over ,Male ,Nivolumab ,Neutrophils ,Stomach Neoplasms ,Humans ,Female ,Lymphocytes ,Middle Aged ,Prognosis ,Aged ,Retrospective Studies - Abstract
Immune checkpoint inhibitors(nivolumab)have been recommended as third-line chemotherapy for advanced gastric cancer(AGC)according to the Guidelines of Gastric Cancer(5th edition). Therefore, they have been used in daily clinical practice. On the other hand, the neutrophil-lymphocyte ratio(NLR)has been reported to be associated with the prognosis of cancer patients.Twenty patients treated with nivolumab for AGC between January 2018 and November 2019 were retrospectively examined.Median age of the 20 patients(18 males, 2 females)was 70 years(55- 84 years). Nivolumab was administered as second-, third-, fourth-, and fifth-line therapy in 1, 11, 7, and 1 case, respectively. The best tumor response evaluation was observed in PR 1, SD 7 and PD 10 cases. Median overall survival(OS)was 10 months, and median progression-free survival(PFS)was 3 months. No serious adverse events occurred. Compared to the NLR2.0 group, OS significantly prolonged(2.2 months vs 21.9 months)and PFS tended to prolong(1.4 months vs 6.2 months)in the NLR≤2.0 group.NLR may be an effective prognostic factor in patients with AGC receiving nivolumab treatment.
- Published
- 2020
6. Lack of Inferior Mesenteric Artery in a Sigmoid Colon Cancer
- Author
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Nobuhiro Haruki, Koshiro Harata, Hideki Tsuji, and Sunao Ito
- Subjects
medicine.medical_specialty ,Sigmoid colon cancer ,business.industry ,Internal medicine ,medicine.artery ,Gastroenterology ,Medicine ,Surgery ,business ,Inferior mesenteric artery - Published
- 2018
7. A Case of Sigmoid Colon Cancer with Intestinal Malrotation Treated by Laparoscopic Surgery
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Hideki Tsuji, Nobuhiro Haruki, Koji Mizoguchi, Sunao Ito, Koshiro Harata, and Hiroki Kurehara
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Laparoscopic surgery ,medicine.medical_specialty ,business.industry ,General surgery ,medicine.medical_treatment ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Sigmoid colon cancer ,Intestinal malrotation ,030220 oncology & carcinogenesis ,medicine ,030211 gastroenterology & hepatology ,business - Published
- 2017
8. Laparoscopic Surgery for Traumatic Intramural Hematoma of the Jejunum—A Case Report—
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Korehito Takasu, Sunao Ito, Nobuhiro Haruki, Hiroki Kurehara, Koji Mizoguchi, and Hideki Tsuji
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Jejunum ,Laparoscopic surgery ,medicine.medical_specialty ,medicine.anatomical_structure ,Intramural hematoma ,business.industry ,medicine.medical_treatment ,General surgery ,medicine ,business ,Surgery - Published
- 2016
9. A case of superior mesenteric artery syndrome treated with laparoscopic duodenojejunostomy
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Koji Mizoguchi, Koshiro Harata, Hiroki Kurehara, Tsutomu Tatematsu, Hideki Tsuji, and Nobuhiro Haruki
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medicine.medical_specialty ,business.industry ,General surgery ,medicine ,business ,medicine.disease ,Superior mesenteric artery syndrome ,Surgery - Published
- 2012
10. A case of a ruptured idiopathic mesenteric abscess successfully treated by laparoscopic-assisted surgery
- Author
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Nobuhiro Haruki, Yukio Terashita, Yoichiro Mori, Koshiro Harata, Atsushi Sato, and Akihiro Naito
- Subjects
medicine.medical_specialty ,business.industry ,General surgery ,medicine ,Mesenteric abscess ,business ,Surgery - Published
- 2012
11. SURGICAL TREATMENTS AND OUTCOMES FOR COLORECTAL CARCINOMA IN PATIENTS ON HEMODIALYSIS
- Author
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Atsushi Sato, Nobuhiro Haruki, Yoichiro Mori, Yukio Terashita, Koshiro Harata, and Shinichiro Saito
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Oncology ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,Internal medicine ,medicine.medical_treatment ,medicine ,Urology ,In patient ,Hemodialysis ,medicine.disease ,business - Abstract
2003年3月から2010年9月までの7.5年間に当科で経験した透析患者の大腸癌手術症例について臨床的検討を行った.術前併存疾患は多種多様で高血圧,糖尿病,冠動脈疾患が多かった.手術は,待機手術が18例,緊急手術が2例に施行された.開腹手術が16例,腹腔鏡下手術が3例,腹腔鏡下手術から開腹手術へ移行した症例が1例であった.いずれの症例にも根治切除が可能であった.再建は19例に施行され,人工肛門が造設されたのは緊急手術の1例のみであった.術後合併症は5例(25%)に認めたが,全例が保存的に軽快した.透析患者に対する外科手術は以前より安全に施行できるようになり,根治性と生活の質を考慮した術式の選択が可能となってきた.しかし,重篤な合併症症例が多く,患者の高齢化や透析期間の長期化もあり,依然として高リスクである.周術期の慎重な管理と,長期的には他病死に対する注意が必要と考えられた.
- Published
- 2011
12. γ-Secretase Inhibitor Prevents Notch3 Activation and Reduces Proliferation in Human Lung Cancers
- Author
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Keiko S. Kawaguchi, Nobuhiro Haruki, Huan Vo, Adriana Gonzalez, Thao P. Dang, David P. Carbone, and Jun Konishi
- Subjects
Cancer Research ,Small interfering RNA ,Lung Neoplasms ,Notch signaling pathway ,Mice, Nude ,Antineoplastic Agents ,Biology ,Mice ,Carcinoma, Non-Small-Cell Lung ,Thiadiazoles ,medicine ,Animals ,Humans ,Enzyme Inhibitors ,HES1 ,Lung cancer ,Receptor ,Receptor, Notch3 ,Cell Proliferation ,Receptors, Notch ,Cell growth ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,Cyclic S-Oxides ,Gene Expression Regulation, Neoplastic ,Oncology ,Immunology ,Disease Progression ,Cancer research ,Amyloid Precursor Protein Secretases ,Apoptosis Regulatory Proteins ,Targeted therapy of lung cancer ,Signal Transduction - Abstract
Notch receptors are key regulators of development by controlling cell-fate determination in many multicellular organisms. Genes that are important for normal differentiation play a role in cancer when their normal functions became dysregulated. Notch signaling has been shown to promote and maintain survival of many types of cancers, and we previously have shown that Notch3 plays an important role in lung cancer. In this study, we showed that a high percentage of lung cancer lines expressed Jagged1, Notch receptors, and their transcriptional target genes (HES1, Hey1), suggesting that the Notch pathway plays an important role in lung cancer biology. Thus, inhibition of Notch receptor activation represents a compelling treatment strategy. Notch activation requires proteolytic cleavage of the receptor by γ-secretase protein complex. In this study, we determined the ability of MRK-003, a γ-secretase inhibitor, to inhibit Notch3 signaling, growth, and apoptosis of lung cancer cell lines in vitro and in vivo using mouse xenograft models. We also found that MRK-003 inhibited Notch3 signaling, reduced tumor cell proliferation, inhibited serum independence, and induced apoptosis. This drug had no effect when Notch3 expression was knocked down using small interfering RNA (siRNA), suggesting that the observed effects were mediated by specific action on this receptor. In conclusion, these results support the hypothesis that inhibition of Notch activation using a γ-secretase inhibitor represents a potential new approach for the targeted therapy of lung cancer. [Cancer Res 2007;67(17):8051–7]
- Published
- 2007
13. Thioredoxin-1 Modulates Transcription of Cyclooxygenase-2 via Hypoxia-Inducible Factor-1α in Non–Small Cell Lung Cancer
- Author
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Nobuhiro Haruki, Jason D. Morrow, David H. Johnson, Ildiko Csiki, David P. Carbone, Kiyoshi Yanagisawa, and Sorena Nadaf
- Subjects
Transcriptional Activation ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Transcription, Genetic ,Biology ,Transfection ,Thioredoxins ,Transcription (biology) ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Internal medicine ,Gene expression ,medicine ,Humans ,RNA, Messenger ,Promoter Regions, Genetic ,Lung cancer ,Gene ,Transcription factor ,Cancer ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Cell Hypoxia ,Endocrinology ,Oncology ,Hypoxia-inducible factors ,Cyclooxygenase 2 ,Enzyme Induction ,Cancer research ,Thioredoxin - Abstract
Hypoxic induction of gene expression occurs mainly via the hypoxia-inducible factor-1 (HIF-1) transcription factor and is a critical step in tumor growth. Cyclooxygenase-2 (COX-2) is commonly overexpressed in non–small cell lung cancer (NSCLC). In this study, we sought to determine the role of HIF-1 in the induction of COX-2 expression during hypoxia. Through sequence comparison of hypoxia-responsive genes, COX-2 promoter deletion analysis, and site-directed mutagenesis, we identified a hypoxia-responsive element within the COX-2 promoter that interacts with HIF-1α and underlies the mechanism of hypoxic activation of COX-2 in lung cancer cells. Proteomic analysis of NSCLC identified thioredoxin-1 as a redox protein overexpressed in NSCLC correlated with poor prognosis. We also show that thioredoxin-1 stabilizes HIF-1α to induce hypoxia-responsive genes under normoxic conditions. Our results identify two new mechanisms for regulation of COX-2 expression in NSCLC. (Cancer Res 2006; 66(1): 143-50)
- Published
- 2006
14. Expression of PPAR-gamma is correlated with the clinical course of neuroblastoma
- Author
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Hidefumi Sasaki, Tatsuya Toyama, Yoko Sato, Yoshihiro Kobayashi, Nobuhiro Haruki, Satoshi Kondo, and Yoshitaka Fujii
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Male ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Urinary system ,Cellular differentiation ,Nervous System Neoplasms ,Receptors, Cytoplasmic and Nuclear ,Peroxisome proliferator-activated receptor ,Neuroblastoma ,Vanilmandelic Acid ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,Receptor ,Neoplasm Staging ,chemistry.chemical_classification ,Ploidies ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Infant ,Histology ,General Medicine ,medicine.disease ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Endocrinology ,chemistry ,Nuclear receptor ,Neoplasm Regression, Spontaneous ,Pediatrics, Perinatology and Child Health ,Female ,Surgery ,business ,Transcription Factors - Abstract
Background/Purpose: Neuroblastoma is a common pediatric tumor of the sympathetic nervous system. Unlike the ones found in older children, the tumors found in patients younger than one year of age often show spontaneous differentiation and regression. Peroxisome proliferator-activated receptor gamma (PPAR-γ), a member of the nuclear hormone receptor superfamily is expressed in several human cancers. Recently, PPAR-γ has been reported to be expressed in neuroblastoma, and the agonist of this receptor caused differentiation of neuroblastoma cells. Methods: In this report we studied the expression of PPAR-γ mRNA, using LightCycler in neuroblastoma samples diagnosed in 17 patients under the age of one year. Results: Twelve samples showed PPAR-γ mRNA expression. There was no significant difference in the PPAR-γ mRNA expression based on age, histology, staging, and DNA ploidy. The PPAR-γ mRNA expression level was significantly correlated with the change in urinary vanillyl mandelic acid (VMA). The neuroblastoma samples resected from patients who showed a decrease in their urinary VMA before the operation showed significantly higher PPAR-γ expression than those from patients who showed an increase in their urinary VMA before the operation. Conclusions: PPAR-γ may have played a role in the reduction of VMA and possibly in the regression of early-onset neuroblastoma. J Pediatr Surg 38:205-210. Copyright 2003, Elsevier Science (USA). All rights reserved .
- Published
- 2003
15. Estrogen receptor α mutation (A-to-G transition at nucleotide 908) is not found in different types of breast lesions from japanese women
- Author
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Tatsuya Toyama, Hirotaka Iwase, Hiroshi Sugiura, Shunzo Kobayashi, Yoko Omoto, Nobuhiro Haruki, Hiroko Yamashita, Yasuo Hara, and Zhenhuan Zhang
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Adult ,Estrogen receptor ,Breast Neoplasms ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Breast Diseases ,Breast cancer ,Germline mutation ,Asian People ,Japan ,medicine ,Humans ,Pharmacology (medical) ,Radiology, Nuclear Medicine and imaging ,skin and connective tissue diseases ,Estrogen receptor beta ,Aged ,Mutation ,Transition (genetics) ,Carcinoma, Ductal, Breast ,Sequence Analysis, DNA ,General Medicine ,Middle Aged ,Hyperplasia ,medicine.disease ,Carcinoma, Intraductal, Noninfiltrating ,Receptors, Estrogen ,Oncology ,Cancer research ,Female ,Precancerous Conditions ,Estrogen receptor alpha ,Polymorphism, Restriction Fragment Length - Abstract
An estrogen receptor (ER) alpha variant with an A-to-G transition at nucleotide 908 (A908G) has been identified in typical hyperplastic mammary epithelium. This somatic mutation, which induces a Lys-to-Arg substitution at residue 303 within exon 4 at the border of the hinge and hormone-binding domains of the ER alpha, shows increased sensitivity to estrogen compared with wild-type ER alpha.To investigate whether this mutation was present in breast lesions, we performed mutation analyses using the PCR-restriction fragment length polymorphism (RFLP) method in 7 cases of hyperplasia, 18 cases of benign breast tumor, 26 cases of ductal carcinoma in situ (DCIS) and 215 cases of invasive ductal carcinoma (IDC). When we extracted DNA, the hyperplastic epithelium and cancer cells of DCIS were microdissected. We also performed direct sequencing analysis from 7 randomly-selected representative cases of hyperplasia, 9 cases of benign breast tumors, 11 cases of DCIS and 20 cases of IDC.No A908G mutation was found in the ER alpha gene in these breast lesions.This mutation might be absent or occur in so few cells as to be undetectable by PCR-RFLP or direct sequencing.
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- 2003
16. Expression of PTTG (Pituitary Tumor Transforming Gene) in Esophageal Cancer
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Nobuhiro Haruki, Yasuyuki Shibata, Hideyuki Ishiguro, Junzo Kudo, Yoshiyuki Kuwabara, Tadashi Nishiwaki, Noriyuki Shinoda, Shigeru Konishi, Yukio Terashita, Yoshitaka Fujii, Atsushi Sato, Joji Kato, Masahiro Kimura, Tatsuya Toyama, and Hiroshi Koyama
- Subjects
Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Esophageal Neoplasms ,Pituitary neoplasm ,medicine.disease_cause ,Malignant transformation ,medicine ,Adjuvant therapy ,Humans ,Radiology, Nuclear Medicine and imaging ,RNA, Messenger ,Esophagus ,Survival rate ,Aged ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,General Medicine ,Middle Aged ,Esophageal cancer ,Prognosis ,medicine.disease ,Neoplasm Proteins ,Securin ,Survival Rate ,Reverse transcription polymerase chain reaction ,medicine.anatomical_structure ,Oncology ,Cancer research ,Female ,business ,Carcinogenesis - Abstract
Background: Recently, a vertebrate securin [pituitary tumor transforming gene (PTTG) in humans] has been identified that inhibits sister chromatid separation and is involved in malignant transformation and tumorigenesis. Abundance of this protein would disrupt cell division, generate chromosomal instability and thereby increase cell susceptibility to acquisition of further mutations during subsequent division. Esophageal cancer is a disease with poor prognosis with early local invasion and lymph node metastasis. It is important to identify factors that influence the aggressiveness of esophageal cancer. Methods: Expression of PTTG messenger ribonucleic acid (mRNA) was evaluated by real-time reverse transcription polymerase chain reaction in 48 esophageal cancer specimens and matched normal esophageal mucosa. The data were analyzed with reference to clinicopathological factors. Results: Tumor tissue expressed a significantly higher level of PTTG1 mRNA than the corresponding normal tissue (P < 0.0001). PTTG1 mRNA expression was significantly higher in tumors with higher pathological stage (IV vs 0-III, P = 0.0442) or more extensive lymph node metastasis (pathological N factor; N4 vs N0-3, P = 0.003). The median survival for patients with high PTTG1 expression (8.5 months) was less than that for patients with low PTTG1 expression (14.0 months, P = 0.039). PTTG1 expression was one of the significant predictors of survival on univariate analysis (hazard ratio 2.225; 95% confidence interval 1.007-4.915). Conclusions: Detection of high PTTG1 expression in surgically excised esophagus tumor tissues might help to identify patients with aggressive disease who require adjuvant therapy and provide prognostic information.
- Published
- 2002
17. Persistent Increase in Chromosome Instability in Lung Cancer
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Akira Masuda, Hirotaka Osada, Tomoko Harano, Yoshio Tatematsu, Hiroyuki Konishi, Takao Takahashi, Nobuhiro Haruki, Shigeki Shimizu, Yoshitaka Fujii, Tetsuya Mitsudomi, Tohru Kiyono, and Takashi Takahashi
- Subjects
Mutation ,medicine.diagnostic_test ,Aneuploidy ,Karyotype ,Biology ,medicine.disease ,medicine.disease_cause ,female genital diseases and pregnancy complications ,Pathology and Forensic Medicine ,Spindle apparatus ,Chromosome instability ,medicine ,Cancer research ,Lung cancer ,Mitosis ,Fluorescence in situ hybridization - Abstract
Karyotype and fluorescence in situ hybridization analyses have demonstrated the frequent presence of an altered static state of the number of chromosomes (ie, aneuploidy) in lung cancer, but it has not been directly established whether aneuploidy is in fact associated with a persistent increase in the rate of chromosomal losses and gains (ie, chromosome instability, or CIN). The study presented here used a panel of 10 lung cancer cell lines to provide for the first time direct evidence that CIN is a common feature in lung cancer cell lines in association with the presence of significant aneuploidy. In addition, we found that the CIN phenotype correlates well with the presence of p53 mutations. However, human papilloma virus 16-E6-directed inactivation of p53 in a representative non-CIN lung cancer cell line did not result in the induction of CIN, at least up to the 25th generation, suggesting that inactivation of p53 itself is unlikely to directly induce CIN in lung cancer cells. Interestingly, however, significant CIN could be induced in conjunction with the generation of aneuploid populations when the mitotic spindle formation was transiently abrogated in p53-inactivated cells. These results suggest that inactivation of p53 may allow lung cancer cells to go through an inappropriate second division cycle under certain forms of mitotic stresses, which would result in the induction of the CIN phenotype in conjunction with the generation of aneuploidy.
- Published
- 2001
18. Expression of human telomerase subunit genes in primary lung cancer and its clinical significance
- Author
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Mitsuyuki Arinaga, Shigeki Shimizu, Takao Takahashi, Kunihiko Gotoh, Tetsuya Mitsudomi, Takashi Takahashi, and Nobuhiro Haruki
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Telomerase ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Protein subunit ,Adenocarcinoma ,Sensitivity and Specificity ,Catalytic Domain ,Gene expression ,Tumor Cells, Cultured ,Humans ,Medicine ,Telomerase reverse transcriptase ,Lung cancer ,Gene ,Aged ,Aged, 80 and over ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,RNA-Binding Proteins ,RNA-Directed DNA Polymerase ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,DNA-Binding Proteins ,Carcinoma, Squamous Cell ,Cancer research ,RNA ,Biomarker (medicine) ,Female ,Surgery ,Carrier Proteins ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,TEP1 - Abstract
Background . Three major components of human telomerase, RNA component (hTERC), telomerase-associated protein (TEP1), and catalytic subunit (hTERT) have been cloned recently. The aim of this study was to examine the expression of these genes and to search for clinical usefulness. Methods . Expression of these genes was evaluated by reverse transcription-polymerase chain reaction in 92 human lung cancers and in 32 non-neoplastic lung tissues. In 15 patients, both telomerase activity by telomeric repeat amplification protocol assay and expression were evaluated. Results . hTERT expression was best associated with telomerase activity with a concordance of 77%. In 92 lung cancer tissues, hTERC, TEP1, and hTERT were expressed in 100%, 93%, and 89%, respectively. Whereas most adjacent non-neoplastic lung tissues expressed hTERC and TEP1 (94% and 100%, respectively), hTERT was detected in only 1 of 32 normal lungs. However, there was no relationship between hTERT expression and clinicopathologic features. Conclusions . hTERT expression can be a surrogate for telomerase activity that may serve as a novel biomarker of lung cancer with high specificity and sensitivity.
- Published
- 2000
19. Frequent allelic imbalance suggests involvement of a tumor suppressor gene at 1p36 in the pathogenesis of human lung cancers
- Author
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Shuji Nomoto, Nobuhiro Haruki, Yoshio Tatematsu, Hiroyuki Konishi, Tetsuya Mitsudomi, Toshitada Takahashi, and Takashi Takahashi
- Subjects
Adult ,Genetic Markers ,Cancer Research ,Candidate gene ,Lung Neoplasms ,Positional cloning ,Tumor suppressor gene ,Chromosome Disorders ,Locus (genetics) ,Biology ,Translocation, Genetic ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Genetics ,medicine ,Humans ,Genes, Tumor Suppressor ,Deletion mapping ,Lung cancer ,Alleles ,Chromosome Aberrations ,Chromosomes, Human, Pair 12 ,medicine.disease ,Chromosome Banding ,Chromosomes, Human, Pair 1 ,Genetic marker ,Allelic Imbalance - Abstract
The short arm of chromosome 1 is among the most frequently affected regions in various types of common adult cancers as well as in neuroblastoma. In a previous study of ours, frequent allelic imbalance at the TP73 locus at 1p36 was noted in lung cancer despite the absence of TP73 mutations. This suggested the possible existence of an as yet unidentified tumor suppressor gene on 1p. Our initial attempt using the candidate gene approach did not yield any somatic mutations in the 14-3-3sigma gene (official gene symbol, SFN), a mediator of G2 arrest by TP53. Detailed deletion mapping of the telomeric region of 1p was thus carried out as an initial step toward positional cloning. We used seven polymorphic markers in addition to TP73 to examine 61 primary lung cancers. Allelic imbalance at one or more loci of 1p36 was observed in 30 of the 61 cases, whereas D1S508 at 1p36.2 exhibited the highest frequency (45%) of allelic imbalance among the 1p36 markers examined. In contrast, two proximal markers at 1p32-34 showed significantly less frequent (11-14%) allelic imbalance. Consequently, the present study identified the shortest region of overlap between D1S507 and TP73, which included the most frequently affected marker, D1S508. In addition, several cases exhibited allelic imbalance confined to a subtelomeric region distal to D1S2845 at 1p36.3. The present findings warrant future studies to identify the putative tumor suppressor gene(s) at 1p36 to gain a better understanding of the molecular pathogenesis of lung cancer. Genes Chromosomes Cancer 28:342-346, 2000.
- Published
- 2000
20. Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers
- Author
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Hirotaka Osada, Takao Takahashi, Shigetoyo Saji, Shuji Nomoto, Takashi Takahashi, Akira Masuda, and Nobuhiro Haruki
- Subjects
Cancer Research ,Lung Neoplasms ,Time Factors ,Cell cycle checkpoint ,Cdc20 Proteins ,DNA Mutational Analysis ,Molecular Sequence Data ,Mitosis ,Antineoplastic Agents ,Cell Cycle Proteins ,Biology ,medicine.disease_cause ,Carcinoma, Non-Small-Cell Lung ,Sequence Homology, Nucleic Acid ,Tumor Cells, Cultured ,Genetics ,medicine ,Humans ,Carcinoma, Small Cell ,Lung cancer ,Molecular Biology ,Mutation ,Base Sequence ,Models, Genetic ,Reverse Transcriptase Polymerase Chain Reaction ,Nocodazole ,Calcium-Binding Proteins ,Proteins ,Cancer ,Cell cycle ,G2-M DNA damage checkpoint ,Flow Cytometry ,medicine.disease ,Repressor Proteins ,Microscopy, Fluorescence ,Mad2 Proteins ,Cancer research ,Carrier Proteins ,Carcinogenesis ,HeLa Cells - Abstract
The mitotic checkpoint is thought to be essential for ensuring accurate chromosome segregation by implementing mitotic delay in response to a spindle defect. To date, however, very little data has become available on the defects of the mitotic checkpoint in human cancer cells. In the present study, impaired mitotic checkpoint was found in four (44%) of nine human lung cancer cell lines. To our knowledge, this is the first demonstration of frequent impairment of the mitotic checkpoint in this leading cause of cancer deaths. As an initial step towards elucidation of the underlying mechanism, we further undertook a search for mutations in a key component of the mitotic checkpoint, known as hsMAD2, and its immediate downstream molecule, p55CDC. No such mutations were found, however, in either 21 lung cancer cell lines or 25 primary lung cancer cases, although we could identify silent polymorphisms and the transcribed and processed hsMAD2 pseudogene that was subsequently mapped at 14q21-q23. The present observations appear to warrant further investigations, such as search for alterations in other components, to better understand the molecular pathogenesis of this fatal disease, and warn against potential misinterpretation when performing mutational analyses for other cancer types based on cDNA templates.
- Published
- 1999
21. A CASE OF ADENOSQUAMOUS CELL CARCINOMA ORIGINATING IN THE STOMACH WITH A MARKED INCREASE IN SERUM CEA
- Author
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Makoto Kataoka, Yukashi Ito, Nobuhiro Haruki, Akimitsu Konishi, Satoshi Taniwaki, Hironori Tanaka, and Yoshihiko Hunato
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,Stomach ,Squamous Differentiation ,Histogenesis ,medicine.disease ,digestive system diseases ,Squamous carcinoma ,medicine.anatomical_structure ,Signet ring cell carcinoma ,Carcinoma ,Medicine ,Adenocarcinoma ,Immunohistochemistry ,business - Abstract
Adenosquamous cell carcinomas originating inthe stomach are relatively rare and serum carcinoembrionic antigen (CEA) is commonly negative. Several pathologic mechanisms have been postulated with respect to the origin of this tumor and still been controversial. We experienced a case of adenosquamous cell carcinoma of the stomach with a marked increase in serum CEA is presented. A 67-year-old man was found to have a carcinoma of the third type of Borrmann's classification. 10.5×8cm in diameter, involving mainly middle part of the gastric body. Histologically there were a squamous cell carcinoma in the center which corresponded to the ulcer bottom, a poorly differentiated adenocarcinoma surrounding the squamous cell carcinoma, and a signet ring cell carcinoma spreading to the pyrolus. Consequently, this tumor was diagnosed as adenosquamous cell carcinoma. Immunohistochemical study of CEA was performed. Adenocarcinoma cells were almost positive, however, some foci were negative near to the component of squamous cell carcinoma. On the other hand, most of squamous carcinoma cells were negative, however, some foci were positive sporadically and positive cells were found mainly in the central area of the solid cell nests. A possible histogenesis of squamous differentiation in the pre-existing adenocarcinoma is considered in the case.
- Published
- 1997
22. A Case of Leiomyoblastoma Originated in the Duodenum
- Author
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Nobuhiro Haruki, Hironori Tanaka, Satoshi Taniwaki, Yukashi Itoh, Yoshihiko Hunato, Makoto Kataoka, and Akimitsu Konishi
- Subjects
medicine.anatomical_structure ,Gastroenterology ,Duodenum ,medicine ,Surgery ,Anatomy ,Biology - Abstract
平滑筋芽細胞腫は胃に発生する場合がほとんどで, 十二指腸原発例は少ない.今回, 我々は72歳の女性の十二指腸下行脚に発生した平滑筋芽細胞腫の1例を経験した.十二指腸原発平滑筋芽細胞腫の本邦報告例は過去に22例しかなく, このうち悪性症例は4例で, 1例のみ腫瘍死が確認されている.本症例は, 膵頭十二指腸切除術を施行し, 手術所見や組織学的検索で浸潤傾向やリンパ節転移など悪性所見を認めなかったが, 術後約4年で, 肝転移, 腹水貯留をきたし死亡した.また, 本腫瘍は通常, 類上皮性平滑筋腫瘍と同義語として取り扱われている.しかし, HE染色を中心とした通常観察では, 神経原性腫瘍との鑑別が困難な症例もあり, 本症例でも, 免疫染色によりこの鑑別が可能であった.本腫瘍の組織学的診断に際しては, 通常観察で典型例と判断されても, 免疫染色や電顕を使用した多角的検索により, 平滑筋由来であることを確認する必要があると考えられた.
- Published
- 1997
23. A CASE OF ACUTE CHOLECYSTITIS PROBABLY CAUSED BY FALCIPARUM MALARIA
- Author
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Nobuhiro Haruki, Makoto Kataoka, Yasuyuki Kureyama, Yoshihiko Funato, Hironori Tanaka, Haruhiro Yukiue, Yukashi Ito, and Akimitsu Konishi
- Subjects
Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Anemia ,Gallbladder ,medicine.medical_treatment ,Lumen (anatomy) ,medicine.disease ,Hemolysis ,Muscle hypertrophy ,medicine.anatomical_structure ,Abdominal ultrasonography ,Medicine ,Cholecystectomy ,business ,Malaria - Abstract
A 49-year-old man had infected falciparum malaria during a tour of tropical countries. His symptoms were severe; a high fever and anemia developed and the platelet count decreased. The patient well responded to an antimalarial agent and no Plasmodium had been isolated in the peripheral blood in 18 days. He recovered from malaria, but complained of a right hypochondralgia about one week later. Abdominal ultrasonography revealed hypertrophy of the gallbladder wall and filled debris. A diagnosis of acute cholecystitis was made and a cholecystectomy was performed. Severe inflammation was seen in the vicinity of the gallbladder and its lumen was filled with mucous and black debris. It is thought that indirect reacting bilirubin, which was a metabolite of hemoglobin treated in the reticuloendotherial system due to massive acute hemolysis, was converted to the direct reacting bilirubin in the liver which was excreated into the biliary duct and reabsorbed water in the gallbladder to form debris, causing acute cholecystitis.
- Published
- 1997
24. [Rupture of ileal varices in a type C liver cirrhosis patient: a case report]
- Author
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Takahisa, Suzuki, Mutsumi, Murayama, Masataka, Shinoda, Hitomi, Takashi, Isako, Uchiyama, Kazuhiro, Morise, Akihisa, Usami, Hideki, Tsuji, Nobuhiro, Haruki, Kazuhiro, Tashiro, Takafumi, Ando, and Hidemi, Goto
- Subjects
Liver Cirrhosis ,Varicose Veins ,Rupture, Spontaneous ,Ileum ,Humans ,Female ,Hepatitis C, Chronic ,Aged - Abstract
A 74-year-old woman was admitted to our hospital with recurrent massive lower gastrointestinal bleeding. She had a history of type C liver cirrhosis and appendectomy, and had undergone endoscopic ligation of esophageal varices one year before. Three-dimensional CTA revealed ileal varices in the right lower quadrant of the abdomen. Superior mesenteric arteriography demonstrated varices at the corresponding area and collateral veins from the superior mesenteric vein to the right ovarian vein. Ileal varices were diagnosed and ileal resection was performed. At surgery, exposed vessels were present at the mucosal surface of the resected specimen and they were thought to be the origin of hemorrhage. In conclusion, bleeding from small intestinal varices, though uncommon, should be considered when the origin of melena is unidentified in a patient with liver cirrhosis.
- Published
- 2009
25. [A case of double cancer of sigmoid colon cancer with lung metastases, peritoneal dissemination and early gastric cancer responding to S-1]
- Author
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Masahiko, Sugiura, Hideki, Tsuji, Atsushi, Sato, Nobuhiro, Haruki, Hiroki, Kurehara, Yuzo, Maeda, Yushi, Yamakawa, Tsutomu, Tatematsu, Nanako, Ando, Yorisuke, Maeda, and Yosuke, Yamakawa
- Subjects
Male ,Neoplasms, Multiple Primary ,Antimetabolites, Antineoplastic ,Drug Combinations ,Oxonic Acid ,Sigmoid Neoplasms ,Lung Neoplasms ,Stomach Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Peritoneum ,Aged ,Tegafur - Abstract
A 73-year-old man was referred to our hospital with complaints of constipation and defecation caused by a sigmoid colon tumor. After examination, he was diagnosed as sigmoid colon cancer with lung metastasis, peritoneal dissemination and early gastric cancer. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative day 20, S-1 (100 mg/body for 4 weeks followed by 2 drug-free weeks) treatment was started. After 13 courses of treatment, gastrointestinal fiberscope revealed that the gastric cancer was remarkably reduced, and after 16 courses, computed tomography revealed that the lung metastasis was remarkably reduced. Although after 12 courses, elevation of bilirubin, the treatment could be possible to continued on a lowered dose of S-1 from 100 mg to 80 mg/body. Twenty-four months after the operation, good control of cancer has been maintained, and the treatment is continuing. S-1 treatment was proved effective for double cancer of the advanced colorectal cancer and the gastric cancer.
- Published
- 2009
26. Aberrant nuclear localization of beta-catenin without genetic alterations in beta-catenin or Axin genes in esophageal cancer
- Author
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Hideyuki Ishiguro, Masahiro Kimura, Yasuyuki Shibata, Yukio Terashita, Tadashi Nishiwaki, Junzo Kudo, Yoshitaka Fujii, Hironori Sugiura, Nobuhiro Haruki, Yoshiyuki Kuwabara, and Noriyuki Shinoda
- Subjects
Male ,Beta-catenin ,Esophageal Neoplasms ,Cellular differentiation ,DNA Mutational Analysis ,Nuclear Localization Signals ,lcsh:Surgery ,lcsh:RC254-282 ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Sampling Studies ,Exon ,Cyclin D1 ,Axin Protein ,Reference Values ,Humans ,beta Catenin ,Aged ,Neoplasm Staging ,Probability ,Retrospective Studies ,biology ,Research ,Biopsy, Needle ,Wnt signaling pathway ,lcsh:RD1-811 ,DNA, Neoplasm ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Repressor Proteins ,Wnt Proteins ,Oncology ,Catenin ,Case-Control Studies ,Cancer research ,biology.protein ,Carcinoma, Squamous Cell ,Surgery ,Female ,Nuclear localization sequence ,Signal Transduction - Abstract
Background β-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. β-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of β-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the β-catenin gene and Axin gene in esophageal squamous cell carcinoma. Materials and methods Samples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for β-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the β-catenin gene and Axin gene were performed on tumors with nuclear β-catenin expression. Results Four (8%) esophageal cancer tissues showed high nuclear β-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients. All four cases that showed nuclear β-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of β-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in β-catenin exon 3 in the four cases with nuclear β-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302–2409) which was present in the paired normal mucosa. Conclusion A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of β-catenin accompanied with increased cyclin D1 expression. Mutations in β-catenin or axin genes are not responsible for this abnormal localization of β-catenin.
- Published
- 2006
27. Expression and prognostic roles of PABPC1 in esophageal cancer: Correlation with tumor progression and postoperative survival
- Author
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Nobuhiro Haruki, Yoshiyuki Kuwabara, Takuya Ando, Nobuhiro Takashima, Hiroki Kurehara, Masahiro Kimura, Nobuyoshi Sugito, Yoshitaka Fujii, Hideyuki Ishiguro, and Ryota Mori
- Subjects
Male ,Cancer Research ,Esophageal Neoplasms ,medicine.disease_cause ,Poly(A)-Binding Protein I ,Humans ,Medicine ,RNA, Messenger ,Survival analysis ,Aged ,Oncogene ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Esophageal disease ,Cancer ,General Medicine ,Middle Aged ,Esophageal cancer ,Prognosis ,medicine.disease ,Survival Analysis ,Gene Expression Regulation, Neoplastic ,Reverse transcription polymerase chain reaction ,Oncology ,Tumor progression ,Disease Progression ,Cancer research ,Female ,business ,Carcinogenesis - Abstract
The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict their prognosis, and novel predictive markers of the prognosis of esophageal cancer patients are therefore needed. Poly A binding protein, cytoplasmic 1 (PABPC1) plays a role in post-transcriptional control of mRNA and may be involved in tumorigenesis. PABPC1 expression has not been studied in esophageal cancer. Expression of PABPC1 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 41 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between PABPC1 expression and the clinicopathological factors and prognosis of ESCC patients. Reduced expression of PABPC1 was accompanied by locally invasive tumors (t-factor, p=0.0145) and more advanced tumors (pathologic stage, p=0.0264). Moreover, ESCC patients with low PABPC1 mRNA expression had a significantly shorter postoperative survival time than those with high expression (median survival, 3.1 vs. 6.5 months, p=0.002). In esophageal cancer, reduced expression of PABPC1 was correlated with local tumor progression and poor prognosis after surgery.
- Published
- 2006
28. Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro
- Author
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David P. Carbone, Keiko S. Kawaguchi, Nobuhiro Haruki, John D. Minna, Adriana Gonzalez, Thao P. Dang, S Eichenberger, Pierre P. Massion, and Adi F. Gazdar
- Subjects
Adult ,Lung Neoplasms ,Oncogene Proteins, Fusion ,DNA Mutational Analysis ,Chromosomal translocation ,T-15 ,Biology ,medicine.disease_cause ,Transfection ,Polymerase Chain Reaction ,Translocation, Genetic ,Cell Line ,S Phase ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Lung cancer ,Genetics (clinical) ,Cell Nucleus ,Wild type ,Nuclear Proteins ,medicine.disease ,Blotting, Northern ,Fusion protein ,Molecular biology ,Fusion transcript ,Ectopic expression ,Female ,Original Article ,Carcinogenesis - Abstract
Background: Somatically acquired chromosomal translocation is a common mechanism of oncogene activation in many haematopoietic tumours and sarcomas. However, very few recurrent chromosomal translocations have been reported in more common epithelial tumours such as lung carcinomas. Methods: We established a cell line HCC2429 from an aggressive, metastatic lung cancer arising in a young, non-smoking woman, demonstrating a t(15;19)(q13.2;p13.1). The breakpoints on chromosomes 15 and 19 were cloned using long distance inverse PCR and we determined by RT-PCR that the translocation results in a novel fusion transcript in which the 3' end Brd4 on chromosome 19p is fused to the 5' end of NUT on chromosome 15q. Results: In total, 128 lung cancer tissues were screened using fluorescent in situ hybridisation, but none of the tumours screened demonstrated t(15;19), suggesting that this translocation is not commonly found in lung cancer. Consistent with previous literature, ectopic expression of wild type Brd4 was shown to inhibit G1 to S progression. However, we also found that the Brd4-NUT fusion augments the inhibition of progression to S phase compared with wild type Brd4. Conclusion: Alteration in cell cycle kinetics is important in tumorigenesis, although the exact role of Brd4-NUT fusion protein in the pathogenesis of lung cancers remains unclear and need to be further elucidated.
- Published
- 2005
29. Dominant-negative Notch3 receptor inhibits mitogen-activated protein kinase pathway and the growth of human lung cancers
- Author
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Shannon Eichenberger, Keiko S. Kawaguchi, Nobuhiro Haruki, Thao P. Dang, Adriana Gonzalez, Pierre P. Massion, David P. Carbone, and Sandra J. Olson
- Subjects
Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,MAP Kinase Signaling System ,Receptor expression ,Notch signaling pathway ,Down-Regulation ,Apoptosis ,Cell Cycle Proteins ,Receptors, Cell Surface ,Cell Growth Processes ,Biology ,Transfection ,Immediate-Early Proteins ,Cell surface receptor ,Epidermal growth factor ,Internal medicine ,Cell Line, Tumor ,Protein Phosphatase 1 ,Proto-Oncogene Proteins ,medicine ,Phosphoprotein Phosphatases ,Humans ,Enzyme Inhibitors ,Phosphorylation ,Protein kinase A ,Receptor, Notch3 ,Receptors, Notch ,Dual Specificity Phosphatase 1 ,Tyrphostins ,Cell biology ,ErbB Receptors ,Endocrinology ,Oncology ,Receptor Tyrosine Kinase Inhibition ,Notch proteins ,Quinazolines ,Signal transduction ,Mitogen-Activated Protein Kinases ,Protein Tyrosine Phosphatases - Abstract
Notch3 is a member of an evolutionarily conserved family of cell surface receptors important in cell-fate determination in both vertebrates and invertebrates. Significant data support the role of Notch pathway in cancer development, although the conflicting role of Notch signaling pathways in tumorigenesis suggests that its action is highly context-dependent. Furthermore, although Notch receptors signal primarily through the regulation of hairy enhancer of split (HES) and HES-related (HRT) genes, they are known to crosstalk with other signaling pathways, including the epidermal growth factor (EGF) and the mitogen-activated protein kinase pathways. Whereas much is known about the role of Notch1 in human cancer, the role of Notch3 in epithelial tumors, such as lung carcinomas, has not been well established. In this study, we show that Notch3 is expressed in 80 of 207 (39%) resected human lung tumors and that its expression is positively correlated with EGF receptor expression. Inhibition of the Notch3 pathway using a dominant-negative receptor dramatically reduces growth in soft agar and increases growth factor dependence. We also find that Notch inhibition increases sensitivity to EGF receptor tyrosine kinase inhibition and decrease in phosphorylation of the mitogen-activated protein kinase. These observations support a role for Notch3 signaling in lung cancer, and one potential mechanism of maintaining the neoplastic phenotype is through the modulation of the EGF pathway.
- Published
- 2005
30. Excision repair cross complementing 3 expression is involved in patient prognosis and tumor progression in esophageal cancer
- Author
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Hideyuki Ishiguro, Yukio Terashita, Yoshiyuki Kuwabara, Hironori Sugiura, Nobuhiro Haruki, Yoshitaka Fujii, Tadashi Tanaka, Noriyuki Shinoda, and Masahiro Kimura
- Subjects
Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,DNA Repair ,Esophageal Neoplasms ,Biology ,Esophagus ,medicine ,Carcinoma ,Biomarkers, Tumor ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,RNA, Neoplasm ,Excision repair cross-complementing ,Survival rate ,Aged ,Aged, 80 and over ,Oncogene ,Esophageal disease ,Reverse Transcriptase Polymerase Chain Reaction ,DNA Helicases ,Cancer ,General Medicine ,Esophageal cancer ,Middle Aged ,medicine.disease ,Prognosis ,DNA-Binding Proteins ,Survival Rate ,Oncology ,Tumor progression ,Lymphatic Metastasis ,Cancer research ,Carcinoma, Squamous Cell ,Disease Progression ,Female - Abstract
The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict the prognosis. Therefore, novel predictive markers of the prognosis of esophageal cancer patients are awaited. The abnormality of the nucleotide excision repair (NER) is often involved in human cancers. Excision repair cross complementing 3 (ERCC3) contributes to NER. In esophageal cancer, ERCC3 expression has not been studied. Expression of ERCC3 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 43 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between the ERCC3 expression and the clinicopathological factors and prognosis of ESCC patients. ERCC3 expression level was significantly correlated with the pathologic stage, tumor size and local invasiveness (t-factor) in esophageal cancer tissues. Reduced expression of ERCC3 was accompanied with tumor progression (p=0.0049) and higher pathologic stage (p=0.020). Moreover, ESCC patients with low ERCC3 mRNA expression had significantly shorter post-operative survival time than those with high expression (p=0.0003). In esophageal cancer, reduced expression of ERCC3 was correlated with local tumor progression and poor prognosis after operation.
- Published
- 2004
31. Chfr expression is downregulated by CpG island hypermethylation in esophageal cancer
- Author
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Hironori Sugiura, Yoshiyuki Kuwabara, Noriyuki Shinoda, Yukio Terashita, Nobuhiro Haruki, Tadashi Nishiwaki, Hideyuki Ishiguro, Masahiro Kimura, Shigeru Konishi, Atsushi Sato, Yoshitaka Fujii, Yasuyuki Shibata, Junzo Kudo, Hiroshi Koyama, and Tatsuya Toyama
- Subjects
Male ,Cancer Research ,Esophageal Neoplasms ,Ubiquitin-Protein Ligases ,Cell Cycle Proteins ,Biology ,Adenocarcinoma ,Polymerase Chain Reaction ,CHFR ,Tumor Cells, Cultured ,Gene silencing ,Humans ,Neoplastic transformation ,Poly-ADP-Ribose Binding Proteins ,Mitosis ,Aged ,DNA Primers ,Base Sequence ,General Medicine ,Cell cycle ,DNA Methylation ,Middle Aged ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Tumor progression ,Premature chromosome condensation ,Lymphatic Metastasis ,DNA methylation ,Cancer research ,Carcinoma, Squamous Cell ,Female ,Dinucleoside Phosphates - Abstract
Cell cycle progression is monitored by checkpoint mechanisms to ensure the integrity of the genome and the fidelity of sister chromatid separation. Failure of such checkpoint functions results in genomic instability, a condition that predisposes cells to neoplastic transformation and tumor progression. Recently, Scolnick and Halazonetis defined a new mitotic checkpoint that acts at prophase and delays chromosome condensation in response to mitotic stress, and identified a gene, named checkpoint with FHA and ring finger (Chfr), that seems to be required for delaying prophase in human cells. In the present study, we examined human Chfr mRNA expression in 15 human esophageal cancer cell lines and 43 primary esophageal cancers to investigate the potential involvement of Chfr in the pathogenesis of esophageal cancers. We report here that a significant proportion of human esophageal cancer has loss of expression of Chfr gene. Furthermore, we found aberrant hypermethylation of the promoter region of this checkpoint gene in four of 15 (26.7%) esophageal cancer cell lines and in seven of 43 (16.3%) primary cancers.
- Published
- 2002
32. Molecular analysis of the mitotic checkpoint genes BUB1, BUBR1 and BUB3 in human lung cancers
- Author
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Nobuhiro Haruki, Hiroko Saito, Yoshitaka Fujii, Shuji Nomoto, Hirotaka Osada, Takashi Takahashi, Tomoko Harano, and Takao Takahashi
- Subjects
Cancer Research ,Lung Neoplasms ,BUB3 ,DNA Mutational Analysis ,BUB1 ,Mitosis ,Cell Cycle Proteins ,Biology ,Protein Serine-Threonine Kinases ,medicine.disease_cause ,medicine ,Gene family ,Humans ,Lung cancer ,Poly-ADP-Ribose Binding Proteins ,Gene ,Polymorphism, Single-Stranded Conformational ,Mutation ,Reverse Transcriptase Polymerase Chain Reaction ,Chromosome ,Proteins ,medicine.disease ,Oncology ,Cancer research ,Protein Kinases - Abstract
Our previous studies showed that mitotic checkpoint impairment is present in about 40% of human lung cancer cell lines but that mutations in the MAD mitotic checkpoint genes are infrequent. In the present study, we examined 44 lung cancer cases for the potential involvement of the other gene family involved in the mitotic checkpoint, i.e. BUB. We found that the BUB gene family members including BUB1, BUBR1 and BUB3 are not frequent targets for mitotic checkpoint defects in lung cancers, if present at all. Further studies are thus warranted to elucidate the molecular basis for the acquisition of mitotic checkpoint defects in order to better understand the molecular pathogenesis of lung cancers.
- Published
- 2001
33. Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers
- Author
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Nobuhiro Haruki, Toshitada Takahashi, Takashi Takahashi, Takashi Koshikawa, Yoshitaka Fujii, Takao Takahashi, Akira Masuda, Shuji Nomoto, and Hirotaka Osada
- Subjects
Cancer Research ,Lung Neoplasms ,Somatic cell ,Mitosis ,Single-nucleotide polymorphism ,Cell Cycle Proteins ,Biology ,medicine.disease_cause ,Genetics ,medicine ,Missense mutation ,Humans ,Lung cancer ,Molecular Biology ,DNA Primers ,Mutation ,Base Sequence ,Nuclear Proteins ,Cell cycle ,medicine.disease ,Phosphoproteins ,Repressor Proteins ,Cancer research ,Carcinogenesis ,Carrier Proteins - Abstract
We previously reported the presence of mitotic check-point impairment in about 40% of lung cancer cell lines. To gain an insight into the molecular basis of this impairment, we examined 49 lung cancer specimens for alterations in the hMAD1 mitotic checkpoint gene and identified a somatic, non-conservative missense mutation, which substitutes alanine (GCG) for threonine (ACG) at codon 299, together with a number of amino acid substituting, single nucleotide polymorphisms. This is the first demonstration of hMAD1 mutation in any type of human cancers. The present finding marks hMAD1 as a potential target, although with low frequency, for genetic alterations in lung cancer. Thus, further studies of hMAD1 dysfunction caused by other mechanisms appear to be warranted, as well as potential involvement of other components of the mitotic checkpoint.
- Published
- 1999
34. Cerebral air embolism as a complication of peptic ulcer in the gastric tube: case report
- Author
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Kazuhiro Tashiro, Takafumi Ando, Isako Uchiyama, Akihisa Usami, Hitomi Takashi, Kazuhiro Morise, Masataka Shinoda, Shinya Endo, Takahisa Suzuki, Mutsumi Murayama, Nobuhiro Haruki, and Hidemi Goto
- Subjects
Male ,medicine.medical_specialty ,Peptic Ulcer ,Esophageal Neoplasms ,medicine.medical_treatment ,Case Report ,Gastroenterology ,Air embolism ,Fatal Outcome ,Postoperative Complications ,Internal medicine ,medicine ,Embolism, Air ,Humans ,lcsh:RC799-869 ,Aged ,Intracranial Embolism ,business.industry ,Incidence (epidemiology) ,digestive, oral, and skin physiology ,General Medicine ,Esophageal cancer ,Hepatology ,medicine.disease ,Magnetic Resonance Imaging ,digestive system diseases ,Esophagectomy ,Embolism ,Carcinoma, Squamous Cell ,lcsh:Diseases of the digestive system. Gastroenterology ,Complication ,business ,Tomography, X-Ray Computed - Abstract
Background The reported incidence of ulcer formation in the gastric tube in esophageal replacement is rare. Case Presentation This is the first report of a case of cerebral air embolism as a result of spontaneous perforation of an ulcer in the constructed gastric tube into the pulmonary vein during post-operative follow-up in a patient with esophageal cancer. Conclusions Cerebral air embolism is a rare complication of penetrating gastric ulcer, but should be considered in patients with a history of esophagectomy with gastric conduit that present with acute neurologic findings.
- Published
- 2011
35. Characterization of high-grade neuroendocrine tumors of the lung in relation to menin mutations
- Author
-
Nobuhiro Haruki, William D. Travis, Hirotaka Osada, Shuji Nomoto, Yoshitaka Fujii, Shigeo Nakamura, Yasushi Yatabe, Takashi Takahashi, and Akimasa Nakao
- Subjects
Genetic Markers ,Cancer Research ,Pathology ,medicine.medical_specialty ,endocrine system ,Lung Neoplasms ,Tumor suppressor gene ,endocrine system diseases ,Neuroendocrine tumors ,Biology ,medicine.disease_cause ,Small-cell carcinoma ,Article ,Loss of heterozygosity ,Proto-Oncogene Proteins ,medicine ,Humans ,MEN1 ,Genes, Tumor Suppressor ,Carcinoma, Small Cell ,Multiple endocrine neoplasia ,DNA Primers ,Mutation ,Small cell lung cancer ,Carcinoid tumor ,Menin ,medicine.disease ,Neoplasm Proteins ,Oncology ,Multiple endocrine neoplasia type 1 ,Cancer research ,Large cell neuroendocrine tumor ,Carcinoma, Large Cell ,Carcinogenesis - Abstract
It has been suggested that mutations in the menin gene play a role in the development of multiple endocrine neoplasia type 1 (MEN1)-associated and of sporadic forms of low- and intermediate-grade neuroendocrine tumors of the lung. In the present study, eight tumor specimens of large cell neuroendocrine carcinoma (LCNEC) and 13 of small cell lung cancer (SCLC), which represent a high-grade category of neuroendocrine tumors, were examined for the potential involvement of menin alterations as well as for the expression of various neuroendocrine markers and p53 and Rb abnormalities. All specimens expressed multiple neuroendocrine markers as expected and almost invariably carried p53 and Rb alterations. Unexpectedly, however, mutations in the menin gene were not detected in any of the high-grade neuroendocrine tumors examined. We thus conclude that menin mutations do not play a crucial role in the pathogenesis of high-grade subsets, in contrast to their suggested significant role in the development of low- and intermediate-grade subsets. Interestingly, loss of heterozygosity (LOH) in the menin gene appeared to be more prevalent in LCNEC (50%) than in SCLC (22%), suggesting a possible distinction between SCLC and LCNEC.
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