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Keiji Hayata,
Makoto Iwahashi,
Toshiyasu Ojima,
Masahiro Katsuda,
Takeshi Iida,
Mikihito Nakamori,
Kentaro Ueda,
Masaki Nakamura,
Motoki Miyazawa, Toshiaki Tsuji,
Hiroki Yamaue
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ABSTRACT: It remains controversial whether IL-17A promotes or inhibits cancer progression. We hypothesized that IL-17A that is locally produced in the tumor microenvironment has an important role in angiogenesis and tumor immunity. We investigated the effect of inhibiting IL-17A at tumor sites on tumor growth and on local and systemic anti-tumor immunity. MC38 or B16 cells were inoculated subcutaneously into mice, and intratumoral injection of an adenovirus vector expressing siRNA against the mouse IL-17A gene (Ad-si-IL-17) significantly inhibited tumor growth in both tumor models compared with control mice. Inhibition of IL-17A at tumor sites significantly suppressed CD31, MMP9, and VEGF expression in tumor tissue. The cytotoxic activity of CD8(+) T cells from tumor-infiltrating lymphocytes in mice treated with Ad-si-IL-17 was significantly higher than in control mice; however, CD8(+) T cells from splenocytes had similar activity levels. Suppression of IL-17A at tumor sites led to a Th1-dominant environment, and moreover, eliminated myeloid-derived suppressor cells and regulatory T cells at tumor sites but not in splenocytes. In conclusion, blockade of IL-17A at tumor sites helped suppress tumor growth by inhibiting angiogenesis as well as cytotoxic T lymphocytes activation at tumor sites.
PLoS ONE 01/2013; 8(1):e53131. · 4.09 Impact Factor
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Toshiaki Tsuji,
Mikihito Nakamori,
Makoto Iwahashi,
Masaki Nakamura,
Toshiyasu Ojima,
Takeshi Iida,
Masahiro Katsuda,
Keiji Hayata,
Yasushi Ino,
Tomoki Todo,
Hiroki Yamaue
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ABSTRACT: Advanced gastric cancer is a common disease, but the conventional treatments are unsatisfactory because of the high recurrence rate. One of the promising new therapies is oncolytic virotherapy, using oncolytic herpes simplex viruses (HSVs). Thrombospondin-1 (TSP-1) suppresses tumor progression via multiple mechanisms including antiangiogenesis. Our approach to enhance the effects of oncolytic HSVs is to generate an armed oncolytic HSV that combines the direct viral oncolysis with TSP-1-mediated function for gastric cancer treatment. Using the bacterial artificial chromosome (BAC) system, a 3rd generation oncolytic HSV (T-TSP-1) expressing human TSP-1 was constructed for human gastric cancer treatment. The enhanced efficacy of T-TSP-1 was determined in both human gastric cancer cell lines in vitro and subcutaneous tumor xenografts of human gastric cancer cells in vivo. In addition, we examined the apoptotic effect of T-TSP-1 in vitro, and the antiangiogenic effect of T-TSP-1 in vivo compared with a non-armed 3rd generation oncolytic HSV, T-01. No apparent apoptotic induction by T-TSP-1 was observed for human gastric cancer cell lines TMK-1 cells but for MKN1 cells in vitro. Arming the viruses with TSP-1 slightly inhibited their replication in some gastric cancer cell lines, but the viral cytotoxicity was not attenuated. In addition, T-TSP-1 exhibited enhanced therapeutic efficacy and inhibition of angiogenesis compared with T-01 in vivo. In this study, we established a novel armed oncolytic HSV, T-TSP-1, which enhanced the antitumor efficacy by providing a combination of direct viral oncolysis with antiangiogenesis. Arming oncolytic HSVs may be a useful therapeutic strategy for gastric cancer therapy.
International Journal of Cancer 06/2012; · 5.44 Impact Factor
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Masaki Nakamura,
Makoto Iwahashi,
Mikihito Nakamori,
Teiji Naka,
Toshiyasu Ojima,
Takeshi Iida,
Masahiro Katsuda, Toshiaki Tsuji,
Keiji Hayata,
Shuuichi Mastumura,
Hiroki Yamaue
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ABSTRACT: We examined clinicopathological features and surgical outcomes in patients with adenocarcinoma in the gastroesophageal junction (GEJ), while also analyzing the survival factors that have a prognostic impact. Between 1991 and 2009, 61 patients with tumors in the GEJ (Siewert type II and III) underwent primary surgical resection. Thirty of 61 patients had type II tumors (49.2%) and 31 had type III tumors (50.8%). The tumor size was larger in type III tumors than type II tumors (P = 0.0026). The overall 5-year survival rates in patients with type II tumors and type III tumors were 44.2 per cent and 41.4 per cent, respectively, with no significant differences (P = 0.1888). The independent survival factors were lower mediastinal lymph node metastasis (P = 0.0323) and a noncurative resection (P = 0.0442). The independent survival factors for patients who underwent curative resections were the tumor size (P = 0.0422), M category (P = 0.0489), and lower mediastinal lymph node metastasis (P = 0.0482). This study showed lower mediastinal lymph node metastasis to be an independent survival factor, and also suggested that lower mediastinal lymph node metastasis was associated with distant metastasis in patients with adenocarcinoma in the GEJ (Siewert type II and III). Therefore, the preoperative early detection of such metastasis is important to improve patient survival.
The American surgeon 05/2012; 78(5):567-73. · 1.28 Impact Factor
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ABSTRACT: The aim of this study was to explore the effects of the abdominal shape index on gastric cancer patients' short-term surgical outcomes of laparoscopy-assisted distal gastrectomy (LADG) in both genders.
This retrospective study included 231 consecutive patients with early gastric cancer who underwent LADG with Billroth I anastomosis between 1998 and 2009. The abdominal shape index of patients was calculated using preoperative abdominal computed tomography scans and the Fat Scan software program.
In male patients, the duration of surgery was longer in patients with a body mass index ≥25 kg/m(2) (P = 0.016), with the anterior to posterior diameter ≥200 mm (P < 0.0001), with the transverse diameter (TD) ≥300 mm (P = 0.030), with the waist ≥85 cm (P = 0.039), and with the visceral fat area (VFA) ≥100 cm(2) (P = 0.029). The intraoperative blood loss was higher in the large TD group (P = 0.049), in the high waist group (P = 0.006), and in the large VFA group (P = 0.007). In female patients, the correlations between these surgical outcomes and this abdominal shape index were not found. No significant relationships between each body shape index and the number of lymph nodes retrieved were found in either gender. Postoperative complications were not associated with the fat volume and abdominal shape index.
Accumulation of fat did not affect short-term surgical outcomes except for the duration of surgery and intraoperative blood loss in male patients.
Langenbeck s Archives of Surgery 12/2011; 397(3):437-45. · 1.81 Impact Factor
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Toshiyasu Ojima,
Makoto Iwahashi,
Mikihito Nakamori,
Masaki Nakamura,
Teiji Naka,
Masahiro Katsuda,
Takeshi Iida, Toshiaki Tsuji,
Keiji Hayata,
Katsunari Takifuji,
Hiroki Yamaue
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ABSTRACT: The survival rate of patients with remnant gastric cancer (RGC) is unfavorable in comparison to that of cancer in the nonresected stomach. However, when RGC is curatively resected, no significant differences have been reported between both groups in regard to survival. The aim of this study is to analyze the clinicopathological factors influencing a curative resection of RGC.
Thirty-eight consecutive patients with RGC from January 1, 1994 through March 31, 2009 were enrolled in this retrospective study.
Their primary diseases were gastric cancers (21; 55.3%) and benign diseases (17; 44.7%). The type of the reconstruction methods of first gastrectomy were Billroth I (28; 73.7%) and Billroth II (10; 26.3%). A total of 31 patients underwent a laparotomy. Twenty patients underwent a curative resection, four patients underwent a palliative resection, and seven underwent a nonresective operation. A total of seven patients underwent an endoscopic resection for early gastric cancer, and all patients received a curative resection. Univariate and multivariate logistic regression analyses were performed to identify the clinicopathological and background factors influencing a curative resection of RGC. A multivariate analysis revealed only an annual follow-up endoscopic examination after the initial gastrectomy to be an independent factor for a curative resection (p=0.016; odds ratio, 35.3).
An annual follow-up endoscopic examination an after initial gastrectomy may be related to improving the prognosis of patients with RGC.
Journal of Gastrointestinal Surgery 11/2009; 14(2):277-81. · 2.83 Impact Factor
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Toshiyasu Ojima,
Makoto Iwahashi,
Mikihito Nakamori,
Masaki Nakamura,
Teiji Naka,
Koichiro Ishida,
Kentaro Ueda,
Masahiro Katsuda,
Takeshi Iida, Toshiaki Tsuji,
Hiroki Yamaue
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ABSTRACT: Overweight (body mass index [calculated as weight in kilograms divided by height in meters squared], > or =25.0) has an effect on surgical results, postoperative complications, and long-term survival in patients with gastric cancer who underwent curative gastrectomy.
Retrospective study from January 1, 1992, through December 31, 2002.
Wakayama Medical University Hospital.
This study included 689 patients who underwent curative gastrectomy (R0). Patients who underwent laparoscopic gastrectomy, gastrectomy with pancreaticoduodenectomy, gastrectomy with another organ resection (liver, colon, or ovary), or gastrectomy with thoracotomy were not included.
Duration of operation, amount of blood loss, incidence of postoperative complications, and survival analysis.
The mean (SD) duration of the operation was longer in the overweight group (315 [75] minutes) than in the normal-weight group (277 [85] minutes) (P < .001). The mean (SD) intraoperative blood loss was larger in the overweight group (882 [764] mL) than in the normal-weight group (536 [410] mL) (P < .001). The rates of postoperative complications (anastomotic leakage, pancreatic fistula, and intra-abdominal abscess) were significantly higher in the overweight group (P < .05). Multivariate logistic regression analysis identified that postoperative complications were significantly associated with being overweight (P = .01) and with undergoing pancreatectomy (P = .03). Disease-specific and overall survival did not show any significant difference between the 2 groups.
Being overweight is not a poor risk factor for survival in patients with gastric cancer, although it is independently predictive of postoperative complications.
Archives of surgery (Chicago, Ill.: 1960) 05/2009; 144(4):351-8; discussion 358. · 4.32 Impact Factor
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ABSTRACT: Pulmonary complications occur most frequently following a transthoracic esophagectomy for esophageal cancer and would get to be lethal occasionally. In this study, we sought to determine the effect of respiratory physiotherapy, corticosteroid administration, and the use of the video-assisted thoracoscopic (VATS) esophagectomy with a small thoracotomy incision, on the incidence of pulmonary complications following a transthoracic subtotal esophagectomy.
Approximately 184 patients who had undergone a right transthoracic subtotal esophagectomy for squamous cell carcinoma of the thoracic esophagus were studied. To reduce the incidence of pulmonary complications, we performed clinical trials using respiratory physiotherapy, corticosteroid administration, and the VATS-esophagectomy surgical technique.
The independent risk factors for pulmonary complications in the multivariate logistic regression analysis were not administering corticosteroids, blood loss greater than 630 ml, and not providing respiratory physiotherapy. In addition, the use of a small surgical incision, less than 10 cm, for the thoracotomy had no effect on the prevention of pulmonary complications.
We concluded that patients with thoracic esophageal cancer could undergo a three-field dissection in comparative safety if the patients were provided with corticosteroid medication in the perioperative period, if the patients received sufficient respiratory physiotherapy, and if surgical blood loss was reduced.
Langenbeck s Archives of Surgery 04/2008; 393(2):127-33. · 1.81 Impact Factor
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ABSTRACT: We report a case of multiple early gastric cancer showing varied histological types associated with gastritis cystica profunda (GCP). A 61-year-old man who had early gastric cancer associated with GCP underwent a distal gastrectomy with lymphadenectomy. Histological examination showed various histological types of cancer -well differentiated, moderately differentiated, poorly differentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma- that had developed independently in the mucosal and submucosal layers of the resected specimen. Furthermore, multiple cysts with a single layer of columnar epithelium were present in the submucosa around the cancerous lesions. However, no neoplastic changes were found in those epithelial cells. Helicobacter pylori was detected in the residual stomach 3 months after surgery. Although the mechanism of the relationship between gastric carcinoma and GCPs is obscure, we speculate that repeated erosion and regeneration induced by chronic inflammation causes multicentric carcinogenesis as well as an aberration of the gastric glands. GCPs may be a risk factor for multiple gastric cancer.
Hepato-gastroenterology 55(84):1150-2. · 0.66 Impact Factor
