Shinichiro Horiguchi

Tokyo Metropolitan Cancer and Infectious Diseases Center, Edo, Tōkyō, Japan

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Publications (17)19.71 Total impact

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    ABSTRACT: Objectives: The aim of the study was to determine the significance of miR-126 and miR-20b in colorectal carcinogenesis. Methods: We analyzed the expressions of miR-126 and miR-20b in 136 colorectal tumors from 39 microsatellite stable (MSS) tumors, 23 high microsatellite instability (MSI-H) tumors, 16 Lynch syndrome, and 58 familial adenomatous polyposis (FAP) tumors including adenoma, intramucosal carcinoma, and invasive carcinoma. Results: All four kinds of tumors showed underexpression of both miR-126 and miR-20b. The frequency of miR-126 downregulation was 100.0% in FAP adenomas, 85.7% in FAP intramucosal carcinomas, 78.9% in invasive carcinomas, 81.3% in Lynch syndrome tumors, 68.4% in MSS tumors, and 65.4% in MSI-H tumors. The frequency of miR-20b downregulation was 64.0% in FAP adenomas, 50.0% in FAP intramucosal carcinomas, 73.3% in invasive carcinomas, 62.5% in Lynch syndrome tumors, 79.5% in MSS tumors, and 91.3% in MSI-H tumors. The current study demonstrated underexpression of miR-126 and miR-20b in various types of colorectal cancer. These findings support the hypothesis that angiogenesis results from underexpressions of miR-126 and miR-20b and occurs as an early event in colorectal carcinogenesis. Conclusions: Underexpression of miR-126 and miR-20b was observed in various types of colorectal cancer, and occurs as an early event of colorectal carcinogenesis in FAP tumors. © 2014 S. Karger AG, Basel.
    Oncology 06/2014; 87(1):58-66. · 2.17 Impact Factor
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    ABSTRACT: Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4. Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients. UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05). UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.
    Gut and Liver 01/2014; 8(1):29-34.
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    ABSTRACT: Angiofibroma of soft tissue is a recently described soft tissue tumor that is characterized by fibroblastic spindle tumor cells with arborizing capillary proliferation. Cytogenetically, it harbors a specific fusion gene involving the nuclear receptor coactivator 2 (NCOA2) gene. We report here additional new pathological and cytogenetic features. A soft tissue tumor in the left thigh of 73‐year‐old female was investigated. Microscopically, histiocytoid tumor cells were scattered in an edematous background with branching capillary proliferation. Immunohistochemically, we identified that the tumor cells were positive for histiocytic markers such as CD68 and CD163. Rearrangement of the NCOA2 gene was detected successfully by chromogenic in situ hybridization; however, abnormal signal patterns were observed in only a small subset of tumor cells. Unlike typical tumors with bland spindle cells, the present tumor needs to be distinguished from myxoid, dendritic and clear cell tumors. This case may suggest that angiofibroma of soft tissue is not in the center of the fibroblastic/myofibroblastic tumor group, but rather shows a fibrohistiocytic nature. We also found intratumor genetic heterogeneity, which is uncommon for a translocation‐associated tumor. Therefore, careful evaluation is required to detect the gene rearrangement in this tumor entity.
    Pathology International 01/2014; 64(5). · 1.72 Impact Factor
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    ABSTRACT: To elucidate the clinical characteristics of IgG4-related dacryoadenitis. Clinical features, laboratory findings, radiological findings, associated diseases, treatment, and prognosis were prospectively examined in 12 patients (seven men, five women; mean age, 60.9 ± 15.1 years) with IgG4-related dacryoadenitis. In addition to eyelid swelling, other ophthalmologic symptoms were observed in seven patients, including diplopia (n = 4), ptosis (n = 2), visual field disturbance (n = 2), eye pain (n = 2), decrease of visual acuity (n = 2), eye-movement disturbance (n = 1), dry eye (n = 1), corneal ulcer (n = 1), and epiphora (n = 1). Swelling of the lacrimal glands was bilateral in half of the patients. Other IgG4-related diseases were present in nine patients, including sialadenitis (n = 5), autoimmune pancreatitis (n = 4), retroperitoneal fibrosis (n = 2), and lymphadenopathy (n = 8). Serum IgG4 levels were significantly higher in patients with other IgG4-related disease (1070 ± 813 mg/dl) than in those without (197 ± 59 mg/dl, p = 0.017). Allergic histories and elevated serum IgE levels were each detected in six patients. Eight patients showed inflammatory extension beyond the lacrimal gland, such as thickened rectus muscle (n = 6), inflammation of the optic nerve (n = 2), and retrobulbar inflammation (n = 3). Steroid therapy was effective in seven patients, but dacryoadenitis relapsed in two patients with markedly higher serum IgG4 levels and autoimmune pancreatitis. IgG4-related dacryoadenitis showed various ophthalmologic symptoms due to extensive inflammation beyond the lacrimal gland, frequent association with other IgG4-related disease or allergic phenomena, and steroid responsiveness.
    Albrecht von Graæes Archiv für Ophthalmologie 12/2013; · 1.93 Impact Factor
  • Yujiro Nakayama, Hirotoshi Horio, Shinichiro Horiguchi, Tai Hato
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    ABSTRACT: Meningiomas are generally benign tumors, but rarely metastasize outside of the central nervous system. A 25-year-old female was admitted to our institute because of an abnormal shadow on her chest x-ray. A computed tomography (CT) scan showed a 3-cm, well- circumscribed mass in the right lower lobe of the lung. We performed thoracotomy and resected three pulmonary tumors at the right lung and diaphragm. Histological examination revealed a benign meningothelial meningioma. Six months later, she complained of heaviness of her head and a head CT scan revealed an intracranial mass. A craniotomy was performed and a brain tumor was found to be histologically identical to the lung tumors. During the 21 years since the first operation, we performed three times of pulmonary and pleural metastasectomies and two times of resection of intracranial local recurrences. All of those tumors were meningothelial meningioma without malignant change. The patient is alive without metastasis after the last resection of metastatic tumors.
    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia. 01/2013;
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    ABSTRACT: The case of a 63-year-old male with a large mass in the pancreatic tail and multiple liver metastases, diagnosed as acinar cell carcinoma of the pancreas with a few scattered endocrine cells by liver biopsy is presented. The S-1 chemotherapy was effective, and partial response was obtained with decreased levels of serum CA19.9 and NSE. Ten months after starting chemotherapy, the tumor began to grow accompanied by marked elevation of serum NSE levels (266 ng/ml). The patient died of liver failure due to multiple liver metastasis 18 months after the initiation of the S-1 chemotherapy. Histological findings at autopsy were acinar cell carcinoma with an endocrine component of more than 30 %; the final diagnosis was mixed acinar-endocrine carcinoma of the pancreas. This pathological change and clinical course may imply that S-1 was effective against the acinar component but less effective against the neuroendocrine component caused by tumor differentiation.
    Clinical Journal of Gastroenterology 01/2013; 6(6).
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    ABSTRACT: Cholangiolocellular carcinoma (CoCC) is a rare malignant primary liver tumor that is considered to originate from the canals of Hering, where hepatic progenitor cells are located. CoCC has various clinicopathological findings, therefore it is difficult to describe a clear diagnostic criteria for CoCC. Reported is a case of a large CoCC in a 45-year-old Japanese woman, which could not be preoperatively diagnosed as CoCC. The final diagnosis of CoCC was determined by pathological observation. Since both the biological behavior and diagnostic criteria of CoCC remain unclear, it is necessary to accumulate more information on CoCCs in order to elucidate these characteristic findings. KeywordsCholangiolocellular carcinoma–Hepatocellular carcinoma–Hepatic progenitor/stem cells–Epithelial membrane antigens
    Clinical Journal of Gastroenterology 01/2011; 4(5):340-346.
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    ABSTRACT: Purpose The liver is the most common site of metastasis in patients with colorectal cancer (CRC), and this is a determinant of the prognosis. However, no reliable molecular predictors of liver metastasis have yet been identified. Methods Sixty-two surgical specimens of colorectal cancer were studied. The first group included 25 patients who achieved a disease-free survival period of at least 6 years (CRC-M0), and the second group included 37 patients with synchronous (n = 22) or metachronous (n = 15) liver metastasis (CRC-M1). SMAD4, p53, and Ki-67 expression levels were assessed immunohistochemically. Results The loss of SMAD4 expression and elevated Ki-67 expression were found significantly more frequently in CRC-M1 patients than in CRC-M0 patients (P = 0.0047 and P = 0.013, respectively). Statistically significant differences were also observed between the CRC-M0 group and the metachronous metastasis group. No difference was seen in the overexpression of p53 between the groups. A combination analysis of SMAD4 and Ki-67 revealed no cases with maintained levels of SMAD4 and a low Ki-67 expression had or developed liver metastasis. Conclusion The loss of SMAD4 expression and elevated Ki-67 expression was therefore found to significantly correlate with liver metastasis, regardless of the time of occurrence, thus indicating these factors to be predictive markers for liver metastasis in patients with CRC.
    Surgery Today 01/2010; 40(3):245-250. · 0.96 Impact Factor
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    ABSTRACT: Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor that commonly arises in the lower extremities but rarely in the mesentery. We report computed tomography (CT) and magnetic resonance imaging (MRI) findings of LGFMS of the small bowel mesentery. On CT, the mass was composed of two components. One component, on its right side, appeared to have isointense attenuation relative to muscle, whereas the other component, on its left side, appeared to have low attenuation. On MRI the mass on the right side showed hypointensity similar to muscle on both T1-and T2-weighted images as well as mostly slight enhancement on contrast-enhanced T1-weighted images. On the other hand, the mass on the left side showed relative hypointensity on T1-weighted images and hyperintensity on T2-weighted images as well as intense enhancement on contrast-enhanced T1-weighted images, suggesting that the tumor contained myxoid tissue. The myxoid area of LGFMS may have a tendency to reveal intense enhancement on contrast-enhanced images.
    Radiation Medicine 06/2008; 26(4):244-7.
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    ABSTRACT: Local treatment often fails in patients with resectable pancreatic cancer due to the postoperative development of distant metastases, especially liver metastases. We determined the prognostic factors for postoperative liver metastases in pancreatic cancer patients following surgical resection with combined radiotherapy. Sixty-four patients with nonmetastatic, resectable pancreatic cancer were entered into this study. All of these patients had pancreatic resection surgery combined with radiotherapy. The development of postoperative liver metastases was carefully followed, and the survival ratio was evaluated using the Kaplan-Meier method. The prognostic importance of clinicopathological factors and molecular characteristics was analyzed by the Cox proportional hazards model. The correlation study was performed using Fisher's exact test. Tumor size, curability, and histological type of differentiation were statistically significant independent prognostic factors. On multivariate analysis, curability and histological type of differentiation were statistically significant. Only tumor size (> or = 3 cm) was significantly correlated with postoperative liver metastases, as well as cyclooxygenase-2 expression. There were three significant prognostic factors in patients with resectable pancreatic cancer who had local therapy. Patients who have a large tumor require particularly careful follow-up for postoperative liver metastases.
    Pancreatology 01/2007; 7(2-3):167-73. · 2.04 Impact Factor
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    ABSTRACT: Breast cancer remains a common disease throughout the world. Here we review new knowledge about early breast cancer obtained during the past 5 years. The prognosis of early breast cancer is generally favorable. Especially, ductal carcinoma in situ has been regarded as a non-life-threatening disease. Therefore, early diagnosis and early onset of the treatment has been important. Early age at menarche, late age at first birth, and late age at menopause are related to breast cancer risk. Examination by mammography and ultrasonography is still the most effective means of detection for premenopausal and postmenopausal women, respectively. Additionally, there have been important advances in MRI, sentinel lymph node biopsy, breast-conserving surgery, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant systemic therapy. Another approach to keeping the disease under control is the elucidation of breast cancer's molecular biological features. Assessment of potential molecular targets can lead to early diagnosis and molecular targeted treatment.
    International Journal of Clinical Oncology 05/2006; 11(2):108-19. · 1.73 Impact Factor
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    ABSTRACT: Lymphangiogenesis plays an important role in several normal and pathological conditions, such as wound healing, pathogen infection, inflammation or the metastasis formation of endothelial malignancies. Vascular endothelial growth factor-C (VEGF-C) and VEGF-D are important and specific regulatory factors for lymphatic endothelial proliferation and lymphangiogenesis. Both growth factors mediate their biological activity mainly by VEGF receptor-3 (VEGFR-3, Flt-4). In this study, we measured intratumoral levels of VEGF-C and VEGFR-3 through enzyme-linked immunosorbent assay (ELISA) in 193 primary breast cancer tissues and examined their prognostic values. A significant correlation was found between the VEGF-C and VEGFR-3 protein levels. High VEGF-C levels were associated with low-grade tumors and a smaller size. Univariate analysis showed that high VEGF-C was significantly associated with a favourable prognosis for disease-free survival (DFS) and overall survival (OS). No significant prognostic value of VEGFR-3 was detected. Multivariate analysis confirmed the independent prognostic value of VEGF-C. The intratumoral VEGF-C level is a significant prognostic indicator of primary breast cancer. An investigation of the mechanisms of VEGF-C protein processing in human cancer tissue should be carried out in the future.
    Oncology Reports 04/2006; 15(3):653-9. · 2.30 Impact Factor
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    ABSTRACT: Few surrogate markers are available for predicting the survival benefit from chemotherapy in primary breast cancer. We examined tumor growth kinetics by assessing cytokeratin 18 neo-epitope (CK18NE), an apoptosis marker detected by M30 antibody and Ki-67 antigen, a proliferation marker detected by MIB-1 antibody in 72 primary breast cancer patients who underwent pre-operative anthracycline-based chemotherapy. Increase in M30 index and decrease in MIB-1 index after the exposure of 2 to 4 cycles of chemotherapy correlated significantly with pathological tumor response. Univariate survival analysis, conducted in the subgroup of 42 patients who underwent CAF (cyclophosphamide, adriamycin and 5-FU) therapy alone, showed that the patients with the high levels of M30 index (>35 counts/1000 tumor cells) and the low levels of MIB-1 index (<140 counts/1000 tumor cells) after chemotherapy had a remarkably favorable prognosis as compared with patients in other categories. In addition, the alteration in growth kinetics by the treatment showed a significant prognostic value. Multivariate analysis also confirmed that the post-treatment growth kinetics was an independent prognostic indicator. These findings suggest that the alteration in growth kinetics revealed by CK18NE and MIB-1 might be a surrogate marker for predicting the survival benefit from chemotherapy in primary breast cancer.
    International Journal of Oncology 08/2004; 25(2):397-405. · 2.66 Impact Factor
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    ABSTRACT: Antibody therapy with trastuzumab has greatly impacted breast cancer treatment. Combination treatment with trastuzumab is regarded currently as a first-line therapy for metastatic breast cancers that overexpress Her-2. It has become routine practice to examine the status of Her-2 expression in primary tumors. The impact of this therapy might be as great as that of endocrine therapy from a historical point of view. A number of new approaches using trastuzumab for seeking individualized treatment are being tested in current clinical trials. We reviewed recent advances in trastuzumab treatment and discuss the future of antibody therapy for breast cancer.
    Breast Cancer 02/2004; 11(1):10-4. · 1.33 Impact Factor
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    ABSTRACT: We report 2 patients with metastatic ovarian tumors of gastric origin who underwent oophorectomy with paraaortic and intrapelvic lymph node dissection, and showed a relatively good outcome. Case 1 A 40-year-old female with gastric cancer located in the MULE area underwent total gastrectomy with D3 lymph node dissection on June 2, 1989. Pathological Stage was IIIB and curability was B according to the JGCA classification. In month 56 after surgery, a left ovarian tumor was detected, and bilateral oophorectomy with paraaortic and intrapelvic lymph node dissection was performed. Signet ring cell carcinoma from the stomach was confirmed in both left ovary and lymph node around the left external iliac artery. In month 51 after the oophorectomy, the patient died from carcinomatous peritonitis. Case 2 A 23-year-old female with gastric cancer located in the M area underwent distal gastrectomy with D3 lymph node dissection on November 1, 2000. Pathological Stage was IV and curability was B according to the JGCA classification. In month 19 after surgery, a left ovarian tumor was detected, and left oophorectomy with paraaortic and intrapelvic lymph node dissection was performed. Poorly differentiated adenocarcinoma from the stomach was confirmed in both left ovary and paraaortic lymph nodes. Chemoradiation therapy was performed for the bone metastasis in lumbar vertebra, which was detected in month 4 after the oophorectomy, and partial response was achieved. As of June 2003, no other malignant lesion has been detected.
    Gan to kagaku ryoho. Cancer & chemotherapy 11/2003; 30(11):1839-43.
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    ABSTRACT: “Linitis plastica” refers to a histological characterization of diffusely infiltrating, poorly differentiated adenocarcinoma. Linitis plastica-type esophageal adenocarcinoma is extremely rare: this is thought to be only the sixth case report of linitis plastica involving the esophagus. A 60-year-old man was referred to our hospital after repeated endoscopic examinations over the course of a few months. Because he complained of dysphagia, upper endoscopy was performed, revealing stenosis with a few mucosal changes of the lower esophagus. Gastroesophageal reflux disease was initially diagnosed, but biopsy revealed adenocarcinoma. At the time of operation, peritoneal metastasis was noted. Macroscopically, the lesion was diffusely infiltrating, almost completely covered with normal squamous epithelium that showed positive staining with iodine. Pathological examination showed poorly differentiated adenocarcinoma. Despite the poor prognosis, the patient survived a comparatively long 18 months following esophagectomy with oral chemotherapy using S-1. Key wordsEsophageal adenocarcinoma-Linitis plastica type-Diffusely infiltrating type
    Esophagus 7(4):225-229. · 0.83 Impact Factor
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    ABSTRACT: Coexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates. Serum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant. Serum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN. In a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.
    Pancreatology 13(4):379-83. · 2.04 Impact Factor