Purpose: The purpose of the present study was to evaluate whether trastuzumab has antitumor effect against pancreatic cancer and whether this effect is concordant with levels of HER-2, which is reportedly overexpressed in pancreatic cancer. We also investigated whether the effect is potentiated in combined therapy with gemcitabine. Experimental Design: Using immunohistochemistry and FACScan, we analyzed HER-2 expression in 16 pancreatic cancer cell lines. The in vitro antiproliferative effect of trastuzumab, alone and in combination with gemcitabine, was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.The in vitro antibody-dependent cell-mediated cytotoxicity of trastuzumab was investigated by 51 Cr release assay. The in vivo antitumor effect of trastuzumab, alone and in combination with gemcitabine, was evaluated in nude mouse xenograft growth. The survival benefit was evaluated in a Capan-1orthotopic implanted nude mouse model. Results: HER-2 expression of 2+ or more was observed in 10 and of 3+ in 2 of the 16 cell lines. No in vitro growth-inhibitory effect of trastuzumab was found in any cell line, but trastuzumab induced antibody-dependent cell-mediated cytotoxicity in proportion to HER-2 expression level. Trastuzumab inhibited tumor growth in Capan-1 (HER-2: 3+) xenografts and prolonged survival in the orthotopic model. These effects were increased by combined therapy with gemcitabine. In contrast, trastuzumab exhibited no antitumor effect against PANC-1 (HER-2: 1+) or SW1990 (HER-2: 2+) xenografts. Conclusions: The antitumor effect of trastuzumab in pancreatic cancer with high HER-2 expression was shown in vitro and in vivo. Clinical application of trastuzumab is expected in pancreatic cancer with 3+ HER-2 expression.
Anaplastic thyroid cancer is one of the most aggressive human malignancies and the outcomes of conventional therapy have been far from satisfactory. Recently, epidermal growth factor receptor (EGFR)-targeted therapy has been introduced as an alternative therapeutic strategy for highly malignant cancers. This study was undertaken to investigate the expression of EGFR in anaplastic thyroid cancer cell lines, and to explore the potential of therapies targeting EGFR as a new therapeutic approach. EGFR was universally expressed in anaplastic cancer cell lines at a variety of levels. Specific EGFR stimulation with epidermal growth factor showed significant phosphorylation of ERK1/2 and Akt, and resulted in marked growth stimulation in an anaplastic thyroid cancer cell line, which highly expressed EGFR. This EGFR-transmitted proliferation effect of the cancer cell line was completely inhibited by gefitinib, an EGFR tyrosine kinase inhibitor. Moreover, growth of xenografts inoculated in mice was inhibited in a dose-dependent manner with 25 -50 mg kg À1 of gefitinib administrated orally. Inhibition of EGFR-transmitted growth stimulation by gefitinib was clearly observed in anaplastic thyroid cancer cell lines. Our results suggested that EGFR-targeted therapy, such as gefitinib, might be worth further investigation for the treatment of anaplastic thyroid cancer.
Additional treatment is necessary for patients with LVI, undifferentiated type, and positive horizontal margin. Careful follow-up may be acceptable for patients with the differentiated type without LVI, especially for the elderly or patients with severe comorbidities.
The surgical treatment should not be denied for patients with ESCC due to overweight and underweight. However, intraoperative prevention and postoperative careful monitoring for anastomotic leakage might be required after esophagectomy for overweight patients with ESCC.
We report a new method of esophagogastrostomy after proximal gastrectomy, side overlap with fundoplication by Yamashita (SOFY) in 2017. Recently, even better treatment results can be obtained by modifying the SOFY method. We describe the technical details of the modified SOFY (mSOFY) after laparoscopic proximal gastrectomy. The stomach was dissected in the short axis direction and the esophagus was dissected in the left and right direction. After the proximal gastrectomy, the bilateral diaphragmatic crus were dissected to enhance gastric elevation. After confirming that the esophagus overlapped more than 5 cm at the center of the remnant stomach (we call it SOFY check), the remnant stomach was suture‐fixed to the dissected diaphragmatic crus. The right wall of the esophageal stump and the remnant stomach were anastomosed using the full length of a 45 mm‐linear stapler. The entry hole was closed in a direction that did not widen the anastomotic hole. Both sides of the esophagus, remnant stomach, and diaphragmatic crus were suture‐fixed on the cranial side 1–2 cm away from the anastomosis. Moreover, the left wall and lower end of the esophagus was suture‐fixed to the remnant stomach. The preserved dorsal esophageal wall is pressed and flattened by pressure from the pseudofornix, which is the reflux prevention mechanism. The mSOFY method had favorable treatment outcomes. In conclusion, mSOFY can be one of the safe and feasible reconstruction methods after laparoscopic proximal gastrectomy.
RESULTS.A complete response was observed in 2 cases and a partial response in 1 First Department of Surgery, Osaka City Uni-11 cases, for an overall response rate of 50%. Patients with good performance versity Medical School, Osaka, Japan.status (PS) (0-1) and differentiated histologic type showed higher response rates (50.0% and 63.6%, respectively) than patients with poor PS (2 or 3) and undifferenti-2 Institute for Pathogenic Biochemistry in Medicine, Taiho Pharmaceutical Company, Tokyo, ated histologic type (28.6% and 35.3%, respectively), although there were no sigJapan.nificant differences. Patients with low serum levels of immunosuppressive acidic protein (IAP) showed a significantly higher response rate (71.4%) than those with high IAP levels (0%). Toxic effects included leukopenia, thrombocytopenia, nausea, and vomiting; these were not life-threatening and did not require treatment interruption.CONCLUSIONS. FP therapy is a promising regimen for patients with advanced and recurrent gastric adenocarcinoma. Serum levels of IAP may predict chemosensitivity.
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