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Neoadjuvant chemoradiotherapy for locally advanced pancreas cancer does not lead to tumor regression
Vol. 213, No. 3S, September 2011
transduced cells, or cells transduced with a non-IG20 targeted shRNA. CONCLUSIONS: IG20 is highly expressed in human CRC and its expression can be inhibited using a lentiviral vector. This experimental model may be utilized to confer TRAIL susceptibility to apoptotic-resistant colon cancer cell lines.
Neoadjuvant chemoradiotherapy for locally advanced pancreas cancer does not lead to tumor regression Vikas Dudeja MD, Sidney P Walker MD, Edward W Greeno MD, Eric H Jensen MD, FACS University of Minnesota, Minneapolis, MN INTRODUCTION: Neo-adjuvant chemo-radiotherapy is proposed to improve resectability of locally-advanced/borderline-resectable pancreas cancer (LAPC). The ability of neo-adjuvant therapy to provide tumor regression has not been reported. METHODS: We reviewed pre and post treatment CT scans of patients undergoing neo-adjuvant chemo-radiotherapy (cisplatin, interferon-alpha, 5-FU, radiation) in a phase II clinical trial for LAPC between 2005 and 2008. Response to therapy was assessed. RESULTS: 15 patients (median age 61years, males 66%) received neo-adjuvant therapy for LAPC during 2005-08. Mean tumor size was 3.9cm. Indications for neo-adjuvant treatment included one or more of the following: Involvement of superior mesenteric artery (SMA) (ⱕ180deg-3 patients, ⬎180deg-1 patient), celiac axis (ⱕ180deg-2 patients, ⬎180deg-3 patients), hepatic artery (HA) (⬎180deg-6 patients), and/or superior mesenteric vein/portal vein (SMV/PV) (ⱕ180deg-6 patients, ⬎180deg-7 patients). 4 of 9 (44.4%) patients with borderline resectable disease (tumor involving ⱕ 180deg circumference of the SMA, short-segment encasement/ abutment of the common HA, or short-segment occlusion of SMV/ PV) were resected after neo-adjuvant therapy. Regression of major vascular involvement was not observed in any patients. No patient with ⬎180deg arterial involvement had tumor regression or resection. Five patients (33%) had disease progression during neoadjuvant therapy. Pre-treatment and post-treatment tumor density (Hounsfield units) was similar (Pre-treatment HU: 60.4⫾6.48, posttreatment HU: 62.2⫾6.5, p⫽0.369). CONCLUSIONS: Neo-adjuvant treatment does not provide tumor regression of LAPC with major vascular involvement. Patient selection for neo-adjuvant trial enrollment should remain focused on borderline disease which may have potential for surgical resection.
Hepatocellular carcinoma arises in an immunosuppressive tumor microenvironment Eric C Sorenson MD, Lee M Ocuin MD, Michael J Cavnar MD, Shan Zeng MD, PhD, Rachel Popow BSc, Ronald P DeMatteo MD, FACS Memorial Sloan-Kettering Cancer Center, New York City, NY INTRODUCTION: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is the third most common
Surgical Forum Abstracts S133
cause of cancer deaths. Various cancers have been shown to evade host anti-tumor immune responses by a number of mechanisms. We hypothesized that HCC development depends on an immunosuppressive microenvironment. METHODS: A preclinical mouse model of HCC was studied in which transgenic expression of the human MYC proto-oncogene in hepatocytes is controlled by administration of oral doxycycline. The resulting liver tumors in HCC mice are grossly and histologically similar to human HCC. Livers, spleens, and portal draining lymph nodes (DLN) were harvested from HCC mice and wild type (WT) littermates and were analyzed by flow cytometry. RESULTS: Liver tumors had a dramatic increase in CD4⫹FoxP3⫹ regulatory T (T reg) cells compared to WT livers (22% vs. 5% of CD4⫹ T cells, p⬍0.05). A similar increase in the Gr-1⫹ myeloidderived suppressor cell (MDSC) population was observed (6.9% vs 2.9% Gr-1⫹ of all immune cells, p⬍0.05). Inactivation of MYC after tumor formation resulted in rapid and sustained tumor regression with a corresponding return of the T reg and MDSC population to WT levels within 3 days. These changes were tumor specific and did not occur in the spleen or DLN. CONCLUSIONS: MYC overexpression in hepatocytes produces an immunosuppressive tumor microenvironment in HCC. Antagonism of MYC or its downstream targets presents an attractive target for antitumor therapy via immune modulation.
A differential microRNA profile distinguishes cholangiocarcinoma from pancreatic adenocarcinoma Amy L Collins MD, Sylwia E Wojcik MS, Wendy L Frankel MD, Hansjuerg Alder PhD, Lianbo Yu PhD, Carlo M Croce MD, Mark Bloomston MD The Ohio State University Medical Center, Columbus, OH INTRODUCTION: Cancers of the bile duct and the pancreas are virtually indistinguishable using conventional histopathological and clinical characteristics. We sought to utilize microRNA (miR) profiling to differentiate these two cancers. METHODS: RNA was harvested from the tumors of patients undergoing curative resection for cholangiocarcinoma (n⫽75) or pancreatic adenocarcinoma (n⫽20) and compared with adjacent normal bile duct or pancreas, respectively. Differential microRNA expression profiles were determined using NanoString® technology. RESULTS: 41 differentially expressed miRs were identified in cholangiocarcinoma (25 overexpressed, 16 underexpressed) and 52 miRs were found in pancreatic adenocarcinoma (30 overexpressed, 22 underexpressed) relative to adjacent normal tissue. Of these two profiles, 15 miRs were commonly dysregulated between tumor types. Eight miRs were similarly over- or underexpressed in cholangiocarcinoma and pancreatic adenocarcinoma whereas the other seven miRs had inverse expression levels. CONCLUSIONS: Cholangiocarcinoma has a distinct miR profile from pancreatic adenocarcinoma. Discrimination between these two tumor types may be possible with as few as seven miRs.
transduced cells, or cells transduced with a non-IG20 targeted shRNA. CONCLUSIONS: IG20 is highly expressed in human CRC and its expression can be inhibited using a lentiviral vector. This experimental model may be utilized to confer TRAIL susceptibility to apoptotic-resistant colon cancer cell lines.
Neoadjuvant chemoradiotherapy for locally advanced pancreas cancer does not lead to tumor regression Vikas Dudeja MD, Sidney P Walker MD, Edward W Greeno MD, Eric H Jensen MD, FACS University of Minnesota, Minneapolis, MN INTRODUCTION: Neo-adjuvant chemo-radiotherapy is proposed to improve resectability of locally-advanced/borderline-resectable pancreas cancer (LAPC). The ability of neo-adjuvant therapy to provide tumor regression has not been reported. METHODS: We reviewed pre and post treatment CT scans of patients undergoing neo-adjuvant chemo-radiotherapy (cisplatin, interferon-alpha, 5-FU, radiation) in a phase II clinical trial for LAPC between 2005 and 2008. Response to therapy was assessed. RESULTS: 15 patients (median age 61years, males 66%) received neo-adjuvant therapy for LAPC during 2005-08. Mean tumor size was 3.9cm. Indications for neo-adjuvant treatment included one or more of the following: Involvement of superior mesenteric artery (SMA) (ⱕ180deg-3 patients, ⬎180deg-1 patient), celiac axis (ⱕ180deg-2 patients, ⬎180deg-3 patients), hepatic artery (HA) (⬎180deg-6 patients), and/or superior mesenteric vein/portal vein (SMV/PV) (ⱕ180deg-6 patients, ⬎180deg-7 patients). 4 of 9 (44.4%) patients with borderline resectable disease (tumor involving ⱕ 180deg circumference of the SMA, short-segment encasement/ abutment of the common HA, or short-segment occlusion of SMV/ PV) were resected after neo-adjuvant therapy. Regression of major vascular involvement was not observed in any patients. No patient with ⬎180deg arterial involvement had tumor regression or resection. Five patients (33%) had disease progression during neoadjuvant therapy. Pre-treatment and post-treatment tumor density (Hounsfield units) was similar (Pre-treatment HU: 60.4⫾6.48, posttreatment HU: 62.2⫾6.5, p⫽0.369). CONCLUSIONS: Neo-adjuvant treatment does not provide tumor regression of LAPC with major vascular involvement. Patient selection for neo-adjuvant trial enrollment should remain focused on borderline disease which may have potential for surgical resection.
Hepatocellular carcinoma arises in an immunosuppressive tumor microenvironment Eric C Sorenson MD, Lee M Ocuin MD, Michael J Cavnar MD, Shan Zeng MD, PhD, Rachel Popow BSc, Ronald P DeMatteo MD, FACS Memorial Sloan-Kettering Cancer Center, New York City, NY INTRODUCTION: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is the third most common
Surgical Forum Abstracts S133
cause of cancer deaths. Various cancers have been shown to evade host anti-tumor immune responses by a number of mechanisms. We hypothesized that HCC development depends on an immunosuppressive microenvironment. METHODS: A preclinical mouse model of HCC was studied in which transgenic expression of the human MYC proto-oncogene in hepatocytes is controlled by administration of oral doxycycline. The resulting liver tumors in HCC mice are grossly and histologically similar to human HCC. Livers, spleens, and portal draining lymph nodes (DLN) were harvested from HCC mice and wild type (WT) littermates and were analyzed by flow cytometry. RESULTS: Liver tumors had a dramatic increase in CD4⫹FoxP3⫹ regulatory T (T reg) cells compared to WT livers (22% vs. 5% of CD4⫹ T cells, p⬍0.05). A similar increase in the Gr-1⫹ myeloidderived suppressor cell (MDSC) population was observed (6.9% vs 2.9% Gr-1⫹ of all immune cells, p⬍0.05). Inactivation of MYC after tumor formation resulted in rapid and sustained tumor regression with a corresponding return of the T reg and MDSC population to WT levels within 3 days. These changes were tumor specific and did not occur in the spleen or DLN. CONCLUSIONS: MYC overexpression in hepatocytes produces an immunosuppressive tumor microenvironment in HCC. Antagonism of MYC or its downstream targets presents an attractive target for antitumor therapy via immune modulation.
A differential microRNA profile distinguishes cholangiocarcinoma from pancreatic adenocarcinoma Amy L Collins MD, Sylwia E Wojcik MS, Wendy L Frankel MD, Hansjuerg Alder PhD, Lianbo Yu PhD, Carlo M Croce MD, Mark Bloomston MD The Ohio State University Medical Center, Columbus, OH INTRODUCTION: Cancers of the bile duct and the pancreas are virtually indistinguishable using conventional histopathological and clinical characteristics. We sought to utilize microRNA (miR) profiling to differentiate these two cancers. METHODS: RNA was harvested from the tumors of patients undergoing curative resection for cholangiocarcinoma (n⫽75) or pancreatic adenocarcinoma (n⫽20) and compared with adjacent normal bile duct or pancreas, respectively. Differential microRNA expression profiles were determined using NanoString® technology. RESULTS: 41 differentially expressed miRs were identified in cholangiocarcinoma (25 overexpressed, 16 underexpressed) and 52 miRs were found in pancreatic adenocarcinoma (30 overexpressed, 22 underexpressed) relative to adjacent normal tissue. Of these two profiles, 15 miRs were commonly dysregulated between tumor types. Eight miRs were similarly over- or underexpressed in cholangiocarcinoma and pancreatic adenocarcinoma whereas the other seven miRs had inverse expression levels. CONCLUSIONS: Cholangiocarcinoma has a distinct miR profile from pancreatic adenocarcinoma. Discrimination between these two tumor types may be possible with as few as seven miRs.