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Kensuke Kumamoto

Publications and source records attributed to Kensuke Kumamoto.

16 recordsLinked to original sources
PubMed2026

Laparoscopic Surgery Is Associated With Reduced Small Bowel Obstruction Risk After Colorectal Cancer Surgery: A Nationwide Cohort Study of 5458 Patients.

INTRODUCTION: Postoperative small bowel obstruction (SBO) is a major complication following colorectal cancer surgery, yet evidence-based prevention strategies remain unclear. We aimed to clarify site-specific risk factors for SBO and evaluate the effectiveness of laparoscopic surgery and adhesion prevention materials (APMs) in preventing SBO after colorectal cancer surgery. METHODS: This retrospective cohort study analyzed 5458 patients who underwent colorectal cancer surgery at 32 Japanese institutions between 2012 and 2014. The primary endpoint was the 5-year risk of SBO. We evaluated the effects of laparoscopic surgery, APM use, and stoma creation on SBO risk. Clinical variables included demographics, tumor site, operative approach, operative details, and postoperative complications. Hospital-level clustering was addressed using mixed-effects logistic regression. RESULTS: Overall SBO incidence was 5.2% (n&#x2009;=&#x2009;283). Rectal cancer had the highest risk, whereas all colonic sites except the descending colon showed significantly lower odds. Laparoscopic surgery was associated with a 42% reduction in odds (OR 0.58; 95% CI 0.45-0.74; p&#x2009;<&#x2009;0.001), with significant reductions in ascending (NNT&#x2009;=&#x2009;22.2, p&#x2009;=&#x2009;0.001) and sigmoid colon surgery (NNT&#x2009;=&#x2009;30.2, p&#x2009;=&#x2009;0.003). APMs showed no protective effect (OR 1.01; 95% CI 0.78-1.32; p&#x2009;=&#x2009;0.94). Stoma creation significantly increased SBO risk (OR 1.84; 95% CI 1.35-2.51; p&#x2009;<&#x2009;0.001). Secondary analysis identified reoperation and postoperative ileus as additional independent risk factors. DISCUSSION: Laparoscopic surgery was associated with reduced long-term SBO risk, with significant benefits in ascending and sigmoid colon surgery. APMs showed no measurable benefit. Stoma creation increased SBO risk, with no observed difference between ileostomy and colostomy.

adhesion prevention material↗
PubMed2026

Neoadjuvant Systemic Therapy for Resectable Intrahepatic Cholangiocarcinoma: From Retrospective Studies to Randomized Evidence.

Complete resection remains the only potentially curative treatment for localized intrahepatic cholangiocarcinoma (iCCA), yet postoperative recurrence is common, particularly in patients with high-risk disease. Neoadjuvant systemic therapy may permit earlier control of occult micrometastatic disease, optimize the delivery of systemic treatment, and provide an in vivo assessment of tumor biology prior to major hepatectomy. These potential benefits must be balanced against treatment-related toxicity, surgical delay, and the risk of disease progression precluding resection. Early evidence was primarily derived from retrospective studies, which yielded inconsistent survival outcomes and exhibited substantial vulnerability to confounding and treatment-selection bias. The single-arm NEO-GAP trial subsequently demonstrated the feasibility of administering neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel followed by surgical resection. More recently, the randomized phase II-III ZSAB-neoGOLP trial showed that neoadjuvant gemcitabine-oxaliplatin, lenvatinib, and toripalimab followed by surgery prolonged median event-free survival compared with upfront surgery (median: 18.0 vs. 8.7 months) without substantially compromising surgical feasibility. However, the interim overall survival analysis was inconclusive, and the generalizability of these findings beyond selected, medically fit patients treated at Chinese centers remains uncertain. This narrative review critically appraises the evolving evidence, discusses patient selection and perioperative treatment, and identifies priorities for future research. Current evidence supports the selective consideration of neoadjuvant therapy in medically fit patients with technically resectable but oncologically high-risk iCCA, rather than its routine use in all resectable cases.

GOLP↗
PubMed2006

Quantitative detection of p53 mutations in plasma DNA from tobacco smokers.

In lung tumors, the p53 tumor suppressor gene is commonly mutated with a characteristic mutation spectrum. The amount of and alterations in plasma DNA, such as mutations in p53, were associated with several cancers. Few studies used quantitative methods of high sensitivity. Previously, we observed p53 mutations in the noncancerous tissue that differed from those in lung tumors using the highly sensitive p53 mutation load assay. Based on our observation of an increased p53 mutation load in nontumorous lung tissue in smokers, we hypothesized that plasma DNA may contain mutant p53 indicative of tobacco smoke exposure and will be an effective biomarker of lung cancer or smoking exposure. We modified the p53 mutation load assay to detect mutations at p53 codons 248 and 249, common mutations in lung cancer, in plasma DNA samples with a sensitivity of 1:5,000. The assay was applied to a set of lung cancer cases (n = 39), hospital controls (n = 21), and population controls (n = 20) from a larger study. Controls were selected to consist of equal numbers of both ever and never smokers. The p53 mutation load (mutated p53 copies per total number of p53 copies) was associated with smoking (P = 0.06), but not with lung cancer (P = 0.59). Most of the individuals with p53 mutations observed in plasma DNA were ever smokers and the p53 mutation load was higher in those who smoked for longer durations (P = 0.04). In summary, we were able to detect p53 mutations in plasma DNA from healthy individuals and our data suggest that p53 mutations in plasma DNA may be a marker of carcinogen exposure from tobacco smoke.

Baltimore↗
PubMed2006

Unique microRNA molecular profiles in lung cancer diagnosis and prognosis.

MicroRNA (miRNA) expression profiles for lung cancers were examined to investigate miRNA's involvement in lung carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate lung cancers from noncancerous lung tissues as well as molecular signatures that differ in tumor histology. miRNA expression profiles correlated with survival of lung adenocarcinomas, including those classified as disease stage I. High hsa-mir-155 and low hsa-let-7a-2 expression correlated with poor survival by univariate analysis as well as multivariate analysis for hsa-mir-155. The miRNA expression signature on outcome was confirmed by real-time RT-PCR analysis of precursor miRNAs and cross-validated with an independent set of adenocarcinomas. These results indicate that miRNA expression profiles are diagnostic and prognostic markers of lung cancer.

Adenocarcinoma↗
PubMed2005

HIF-1alpha induces genetic instability by transcriptionally downregulating MutSalpha expression.

Hypoxia promotes genetic instability by undefined mechanisms. The transcription factor HIF-1alpha is crucial for the cellular response to hypoxia and is frequently overexpressed in human cancers, resulting in the activation of genes essential for cell survival. Here, we demonstrate that HIF-1alpha is responsible for genetic instability at the nucleotide level by inhibiting MSH2 and MSH6, thereby decreasing levels of the MSH2-MSH6 complex, MutSalpha, which recognizes base mismatches. HIF-1alpha displaces the transcriptional activator Myc from Sp1 binding to repress MutSalpha expression in a p53-dependent manner; Sp1 serves as a molecular switch by recruiting HIF-1alpha to the gene promoter under hypoxia. Furthermore, in human sporadic colon cancers, HIF-1alpha overexpression is statistically associated with the loss of MSH2 expression, especially when p53 is immunochemically undetectable. These findings indicate that the regulation of DNA repair is an integral part of the hypoxic response, providing molecular insights into the mechanisms underlying hypoxia-induced genetic instability.

Cell Hypoxia↗
PubMed2005

Pericostal tuberculosis diagnosed by fine needle aspiration biopsy: report of a case with a review of the literature.

We present an 81-year-old woman with pericostal tuberculosis, a rare disease recently, without a past history of pulmonary tuberculosis or tuberculous pleurisy. She developed a subcutaneous nodule on her right chest. She was suspected of skin tuberculosis after the confirmation of acid-fast bacilli in a fine needle aspiration material of the nodule. A tuberculin skin test was strongly positive. The nodule was resected, and preclusive antituberculosis chemotherapy with rifampicin and isoniazid was started. The histological findings included granulomatous changes, central necrosis and Langhans' giant cells. Mycobacterium tuberculosis was identified from a culture of the specimen. About six months after the operation, no erythema, nodule or abscess was observed. We first suspected that she had mammary carcinoma and therefore observed the nodules on the thorax; it is important to differentiate tuberculosis from neoplasms. We also reviewed 22 cases of pericostal tuberculosis in Japan reported in the 15 years from 1976 to 2002.

Aged↗
PubMed2005

ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation.

ING2 is a candidate tumor suppressor gene that can activate p53 by enhancing its acetylation. Here, we demonstrate that ING2 is also involved in p53-mediated replicative senescence. ING2 protein expression increased in late-passage human primary cells, and it colocalizes with serine 15-phosphorylated p53. ING2 and p53 also complexed with the histone acetyltransferase p300. ING2 enhanced the interaction between p53 and p300 and acted as a cofactor for p300-mediated p53 acetylation. The level of ING2 expression directly modulated the onset of replicative senescence. While overexpression of ING2 induced senescence in young fibroblasts in a p53-dependent manner, expression of ING2 small interfering RNA delayed the onset of senescence. Hence, ING2 can act as a cofactor of p300 for p53 acetylation and thereby plays a positive regulatory role during p53-mediated replicative senescence.

Acetylation↗
PubMed2005

[BCA225].

Explore the source record for details and available documents.

Biomarkers, Tumor↗
PubMed2004

Loss of disialyl Lewis(a), the ligand for lymphocyte inhibitory receptor sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) associated with increased sialyl Lewis(a) expression on human colon cancers.

Expression of sialyl Lewis(a) is known to be increased in cancers of the digestive organs. The determinant serves as a ligand for E-selectin and mediates hematogenous metastasis of cancers. In contrast, disialyl Lewis(a), which has an extra sialic acid attached at the C6-position of penultimate GlcNAc in sialyl Lewis(a), is expressed preferentially on nonmalignant colonic epithelial cells, and its expression decreases significantly on malignant transformation. Introduction of the gene for an alpha2-->6 sialyl-transferase responsible for disialyl Lewis(a) synthesis to colon cancer cells resulted in a marked increase in disialyl Lewis(a) expression and corresponding decrease in sialyl Lewis(a) expression. This was accompanied by the complete loss of E-selectin binding activity of the cells. In contrast, the transfected cells acquired significant binding activity to sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7)/p75/adhesion inhibitory receptor molecule-1, an inhibitory receptor expressed on lymphoid cells. These results indicate that the transition of carbohydrate determinants from disialyl Lewis(a)-dominant status to sialyl Lewis(a)-dominant status on malignant transformation has a dual functional consequence: the loss of normal cell-cell recognition between mucosal epithelial cells and lymphoid cells on one hand and the gain of E-selectin binding activity on the other. The transcription of a gene encoding the alpha2-->6 sialyltransferase was markedly down-regulated in cancer cells compared with nonmalignant epithelial cells, which is in line with the decreased expression of disialyl Lewis(a) and increased expression of sialyl Lewis(a) in cancers. Treatment of cancer cells with butyrate or 5-azacytidine induced strongly disialyl Lewis(a) expression, suggesting that histone deacetylation and/or DNA methylation may be involved in the silencing of the gene in cancers.

Antigens, Differentiation, Myelomonocytic↗
PubMed2004

Hypoxia induces adhesion molecules on cancer cells: A missing link between Warburg effect and induction of selectin-ligand carbohydrates.

Cancer cells undergo distinct metabolic changes to cope with their hypoxic environment. These changes are achieved at least partly by the action of transcriptional factors called hypoxia-inducible factors (HIFs). We investigated gene expression in cultured human colon cancer cells induced by hypoxic conditions with special reference to cell-adhesion molecules and carbohydrate determinants having cell-adhesive activity by using DNA-microarray and RT-PCR techniques. Hypoxic culture of colon cancer cells induced a marked increase in expression of selectin ligands, the sialyl Lewis x and sialyl Lewis a determinants at the cell surface, which led to a definite increase in cancer cell adhesion to endothelial E-selectin. The transcription of genes for fucosyltransferase VII (FUT7), sialyltransferase ST3Gal-I (ST3O), and UDP-galactose transporter-1 (UGT1), which are all known to be involved in the synthesis of the carbohydrate ligands for E-selectin, was significantly induced in cancer cells by hypoxic culture. In addition, a remarkable induction was detected in the genes for syndecan-4 (SDC4) and alpha5-integrin (ITGA5), the cell-adhesion molecules involved in the enhanced adhesion of cancer cells to fibronectin. The transcriptional induction by hypoxia was reproduced in the luciferase-reporter assays for these genes, which were significantly suppressed by the co-transfection of a dominant-negative form of HIF. These results indicate that the metabolic shifts of cancer cells partly mediated by HIFs significantly enhance their adhesion to vascular endothelial cells, through both selectin- and integrin-mediated pathways, and suggest that this enhancement further facilitates hematogenous metastasis of cancers and tumor angiogenesis.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2002

Roles of cell adhesion molecules in tumor angiogenesis induced by cotransplantation of cancer and endothelial cells to nude rats.

Roles of cell adhesion molecules mediating the interaction of cancer and endothelial cells in tumor angiogenesis were investigated using new in vitro and in vivo model systems with a cultured murine endothelial cell line (F-2) and human cultured epidermoid cancer cells (A431). The A431 cells exhibited typical in vitro cell adhesion to the endothelial F-2 cells. The initial step of adhesion was mediated by sialyl Lewis(x) (Le(x)) and sialyl Le(a), the carbohydrate determinants expressed on the cancer cells, and E-selectin expressed constitutively on F-2 cells. Prolonged culture led to the implantation of cancer cells into the monolayer of the F-2 cells, which was mediated mainly by alpha(3)beta(1)-integrin. F-2 cells cultured on Matrigel showed evident tube formation, and coculture of F-2 cells with A431 cells led to the formation of A431 cell nests constantly surrounded by tube-like networks consisting of F-2 cells. This in vitro morphogenesis was inhibited by the addition of anti-sialyl Le(x)/Le(a) or anti-beta(1)-integrin antibodies, which led to the formation of cancer cell aggregates that were independent from the F-2 cell networks. This in vitro morphological appearance was exactly reproduced in the in vivo tumors, which were formed when the mixture of A431 and F-2 cells at the ratio of 10:1 were cotransplanted s.c. into the back of nude rats. The tumors of A431 supplemented with F-2 cells were profoundly vascularized throughout by the tubular structures formed by F-2 cells, the lumen of which contained the host rat blood cells. The tumor mass thus formed was an average 5.8-fold as large as control A431 tumors that were grown without F-2 cells. The co-injection of anti-Le(x)/Le(a) or anti-beta(1)-integrin antibodies produced a marked reduction in the size of A431 tumors, which were not vascularized and accompanied an independent tiny remnant clump of F-2 cells. The size of these A431 tumors did not differ significantly from those of control A431 tumors raised without F-2 cells. These results indicate that the interaction of tumor cells and endothelial cells in orderly tumor angiomorphogenesis is highly dependent on the action of cell adhesion molecules mediating the adhesion of cancer cells to endothelial cells, inhibition of which remarkably retards tumor growth and angiogenesis.

Animals↗
PubMed2001

Specificities of N-acetylglucosamine-6-O-sulfotransferases in relation to L-selectin ligand synthesis and tumor-associated enzyme expression.

N-Acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) catalyzes the transfer of sulfate from adenosine 3'-phosphate,5'-phosphosulfate to the C-6 position of the non-reducing GlcNAc. Three human GlcNAc6STs, namely GlcNAc6ST-1, GlcNAc6ST-2 (HEC-GlcNAc6ST), and GlcNAc6ST-3 (I-GlcNAc6ST), were produced as fusion proteins to protein A, and their substrate specificities as well as their enzymological properties were determined. Both GlcNAc6ST-1 and GlcNAc6ST-2 efficiently utilized the following oligosaccharide structures as acceptors: GlcNAcbeta1-6[Galbeta1-3]GalNAc-pNP (core 2), GlcNAcbeta1-6ManOMe, and GlcNAcbeta1-2Man. The ratios of activities to these substrates were not significantly different between the two enzymes. However, GlcNAc6ST-2 but not GlcNAc6ST-1 acted on core 3 of GlcNAcbeta1-3GalNAc-pNP. GlcNAc6ST-3 used only the core 2 structure among the above mentioned oligosaccharide structures. The ability of GlcNAc6ST-1 to sulfate core 2 structure as efficiently as GlcNAc6ST-2 is consistent with the view that GlcNAc6ST-1 is also involved in the synthesis of l-selectin ligand. Indeed, cells doubly transfected with GlcNAc6ST-1 and fucosyltransferase VII cDNAs supported the rolling of L-selectin-expressing cells. The activity of GlcNAc6ST-2 on core 3 and its expression in mucinous adenocarcinoma suggested that this enzyme corresponds to the sulfotransferase, which is specifically expressed in mucinous adenocarcinoma (Seko, A., Sumiya, J., Yonezawa, S., Nagata, K., and Yamashita, K. (2000) Glycobiology 10, 919-929).

Base Sequence↗
PubMedDate not supplied

Colon carcinoma metastasis to the thyroid gland: report of a case with a review of the literature.

Metastasis of colon cancer to the thyroid gland is very rare and we would like to report a case we have experienced, with a review of the literature. A 66-year-old woman noticed a swelling in the anterior neck area and sought medical attention at our department in August 2003. At age 63, she had undergone surgery for cancer of the ascending colon, but subsequently the cancer metastasized to the liver and she underwent an outer hepatic segmentectomy. Fine-needle aspiration cytology indicated adenocarcinoma with characteristic tall columnar cells, confirming our suspicion that metastasis from the ascending colon cancer had already occurred. Furthermore, lung metastasis was also suspected, because several nodules were found in the lungs. On August 13, resection of the left lobe of the thyroid gland and dissection of the cervical lymph nodes were performed. Histopathology showed metastasis of the ascending colon cancer to the thyroid and lymph nodes.

Adenocarcinoma↗