ABSTRACT
OBJECTIVES: Numerous studies have investigated the mechanism of the antitumor effect of tranilast, well known as an antiallergic drug. Herein, we investigated the mechanism of the antitumor effects of tranilast using murine PAN 02 cell line. METHODS: In an allograft mouse model, the number of metastatic sites in the liver was counted. Wound healing and chemoinvasion assay were performed to evaluate migration and invasive ability of PAN 02, respectively. Activities of matrix metalloproteinases (MMPs) were evaluated by gelatin zymography. The expression of cofactors in the activation of MMP-2 was assessed by immunohistochemical staining at the front of metastasis. RESULTS: The number of metastatic sites was reduced in tranilast-treated groups. Migration ability and tumor invasiveness were significantly inhibited by tranilast in a dose-dependent manner. Gelatin zymography revealed inhibition of MMP-2 activity. Immunohistochemical staining showed remarkable attenuation of tissue inhibitor of metalloproteinase (TIMP-) 2 expression in tranilast-treated groups. CONCLUSIONS: Tissue inhibitor of metalloproteinase 2 is necessary for MMP-2 activation with interaction between membrane type 1-MMP and proMMP-2. These results suggested that tranilast may inhibit MMP-2 activation through attenuating TIMP-2 expression, resulting in inhibition of tumor invasion and metastasis. Our results showed possibility of tranilast in clinical application for novel cancer therapy.
Subject(s)
Liver Neoplasms/prevention & control , Neoplasms, Experimental/drug therapy , Pancreatic Neoplasms/drug therapy , ortho-Aminobenzoates/pharmacology , Allografts , Animals , Anti-Allergic Agents/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Matrix Metalloproteinase 2/metabolism , Mice, Inbred C57BL , Neoplasm Invasiveness , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Tissue Inhibitor of Metalloproteinase-2/metabolismABSTRACT
A 48-year-old woman had a left breast mass identified during routine breast cancer screening. The mammogram showed pleomorphic-segmental microcalcifications in the mediolateral-oblique view of the left breast. Ultrasonography showed a hypoechoic mass approximately 3.7 cm in diameter with multiple calcifications. Contrast-enhanced magnetic resonance imaging of the breast showed non-mass like enhancement of approximately 4 cm in diameter in the C area of the left breast. She was diagnosed with glycogen-rich clear cell carcinoma (GRCC) by ultrasound-guided vacuum-assisted biopsy. Nipplesparing mastectomy was performed along with sentinel lymph node biopsy. The intraoperative consultation suggested sentinel lymph node metastasis and we therefore performed axillary lymph node dissection. Pathological examination reported microinvasive carcinomas, 0.4 cm in maximum diameter, and extensive intraductal components, 5 cm in size. The tumor cells were stained on PAS staining, but the stains were digested with diastase. The cells were negative for adipophilin. GRCC was first reported by Hull et al. This is a rare type of breast carcinoma. There is no standard therapy for this disease or any data on the prognosis of breast cancer patients with GRCC.
Subject(s)
Adenocarcinoma, Clear Cell , Breast Neoplasms/pathology , Lymph Nodes/pathology , Neoplasm Micrometastasis , Adenocarcinoma, Clear Cell/chemistry , Adenocarcinoma, Clear Cell/surgery , Axilla/pathology , Breast Neoplasms/chemistry , Breast Neoplasms/surgery , Female , Glycogen/analysis , Humans , Mastectomy , Middle Aged , Prognosis , Sentinel Lymph Node BiopsyABSTRACT
BACKGROUND: Laparoscopic splenic vessel-preserving distal pancreatectomy (lap-SVPDP) is a popular procedure in pancreatic surgery. However, postoperative complications include false aneurysms of the splenic artery, splenic vein stenosis and thrombosis, pancreatic fistulas, abscess, and perigastric varices. METHODS: Eight patients (three men, five women, average age 66.1 years) with benign tumors underwent lap-SVPDP. Lap-SVPDP was performed in the lithotomy position with the head slightly elevated. The splenic vein was peeled longitudinally toward the pancreatic tail. A vessel-sealing system was used to detach the pancreatic body from the greater omentum, and the pancreas was transected using a surgical stapler. RESULTS: Mean operation time was 254 min; mean blood loss was 163 ml; and mean post-surgical hospitalization time was 13 days. No postoperative bleeding from the preserved splenic vessels occurred, and there were no splenic infarcts or splenic abscesses. CONCLUSIONS: For safe performance of lap-SVPDP, the posterior surface of the pancreas should be completely exposed. The splenic vein should be 'peeled away', starting from its central rear, enabling easy detection of its course to avoid inadvertent sealing. With improved operational techniques, lap-SVPDP can be adopted as a standard procedure in pancreatic surgery.
Subject(s)
Laparoscopy , Organ Sparing Treatments , Pancreatectomy/methods , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Splenic Artery , Splenic VeinABSTRACT
Three strains of human esophageal carcinoma xenografts established in our institution were tested against combination chemotherapy in vivo and in vitro. TS-1 plus cisplatin (CDDP) was shown to be an effective combination against two carcinoma strains of moderately-differentiated type. Determination of the thymidylate synthase (TS) demonstrated a higher inhibition of the enzyme by adding CDDP to 5-FU, suggesting biochemical modulation. The remaining strain of poorly-differentiated type was resistant to the combination and an attempt was made to add docetaxel (DTX) to show that the three-drug combination was effective against the strain. Combination chemotherapy including TS-1 and CDDP thus appears to be useful treatment choice for esophageal carcinoma.
