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Peptide YY does not inhibit growth of pancreatic cancer cells through cell cycle arrest
AGAA1409
April 2000
6398 DIFFERENTIAL EXPRESSION OF LEPTIN IN LIPOMATOUS AND NON·LIPOMOTAOUS SOFT TISSUE TUMORS. U. Ritzel, U. Brinck, U. Leonhardt, L. Fuezesi, G. Ramadori, Univ of Goettingen, Goettingen, Germany. INTRODUCTION: Recent evidence suggest that within mesenchymal tissues leptin, a proteohonnone, is exclusively secreted by adipocytes. The main aim of the present study was to analyse the expression of leptin in lipomatous and non-lipomatous tumors. METHODS: 35 cases of lipomatous tumors (6 lipomas, 17 low grade liposarcomas, 12 liposarcomas of grade II and III), and 18 cases of non-lipomatous soft tissue sarcomas (12 MFH, 4 pleomorphic leiomyosarcomas,2 embryonic rhabdomyosarcomas) were stained immunohistochemically for the presence of leptin. One lipoma, a well differenciated and a round cell liposarcoma, were additionally analysed for the presence of leptin mRNA transcripts by RT-PCR. RESULTS: Leptin protein expression was found in all lipomas, 15/17 low grade liposarcomas, including 7 well differenciated and 8 myxoid liposarcomas, 5/12 liposarcomas of grade II and III, including round cell and pleomorphic liposarcomas, and in one of the non-lipomatous sarcomas. Leptin mRNA transcripts were present in all 3 investigated lipomatous tumors. CONCLUSIONS: Leptin is differentially expressed in lipomatous tumors and non-lipomatous sarcomas with fibrohistiocytic and muscle differentiation. Detection of leptin expression in myxoid, round cell, and pleomorphic sarcomas may be helpful to support the histopathological diagnosis of liposarcoma. 6399 PEPTIDE YY AUGMENTS THE INHIBITORY EFFECTS OF AL· PHA·TOCOPHEROL SUCCINATE ON PROSTATE CANCER CELL GROWTH. Amy T. Rose, Tracy Heisler, Shirin Towfigh, Natalie Simon, David W. McFadden, UCLA, Los Angeles, CA. Alpha-tocopherol succinate (ATS) has been shown to induce apoptosis of hormone-refractoryprostate cancer cells in vitro and inhibit cell growth in vivo. Peptide YY (PYY) has growth inhibitory activity against multiple cancer cell lines and is synergistic with ATS against breast cancer cells. No data exists on the impact of PYY and ATS against prostate cancer cell lines, cells similar to breast cancer in their hormonal regulation. Methods: A hormone-refractory human prostate cancer cell line, PC-3, was treated with ATS alone at doses ranging from 10 to 100 mcg/cc, PYY alone at doses of 50 to 500 pmol, or a combination of the two agents. MTT assay was performedat 24, 48, and 72 hours to determinecell viability. Statistical analysis was performed with the Student's t-test. Results: Both ATS and PYY exhibited a growth inhibitory effect on the prostate cancer cells compared to controls. ATS caused decreased cell viability with 50 or 100 mcg/cc by 24 hours (p
cell lines. Further work needs to be initiated to further characterize the mechanism of the growth inhibitory effects of PYY.
Percentage of Cells per Phase of Cell Cycle Untreated
Treated
pvalue 0.308 0.432 0,338
GO-G1
71.35
72,09
S
16.82
16,55
G2·M
11 .84
11 ,37
6401 MICROSATELLITE INSTABILITY IN INFLAMMATORY BOWEL DISEASE. Valentina Rovella, Marcello Anti, Maurizio Genuardi, Fabio M. Vecchio. Sandro Rinelli, Alfredo Pastorelli, Antonio Gasbarrini, Giovanni Neri, Giovanni Gasbarrini, Catholic Univ of Rome; Catholic Univ of Rome, Rome, Italy; Institute of Med Genetics, Catholic Univ of Rome, Rome, Italy; Italy. Long-standing Inflammatory Bowel Disease (18D) is a condition at increased colon cancer risk. Mutation or "instability" of microsatellite DNA sequences (MSI) are markers for mutation of genes which are involved in the DNA mismatch repair (MMR)system. MSI has previously reported in non cancerous mucosa of patients with Ulcerative Colitis (UC) and it has been speculated that this finding may be due to an oversaturation of MMR system associated to an increase of epithelial cell proliferation, caused by chronic inflammation. METHODS: In this study we analized five microsatellite markers (02S123, BAT-26, BAT-25, IGFIIR, TGFf3IIR) in biopsy samples taken from 20 patients with UC and 4 patients with Crohn's Disease (CD). Clinical activity, endoscopic and histological scores, degree of inflammationand the presence or absence of high-grade dysplasia were recorded for each patient. RESULTS: Frameshift mutation in the poly(A)IO tract of BAT-26 was found in only one case of CD. Tissue in which MSI was observed had been taken from the right-colon; no dysplasia was found and only a moderate inflammation was present in the sample. No MSI was detected in other colonic areas of the same patient. CONCLUSIONS: In contrast with previous reports, MSI was very rare in this series of patients with IBD. However the detection of MSI in non dysplastic mucosa and in absence of intense inflammation , raises the question whether MSI can be used as an early predictor marker for colon cancer risk. 6402 COLONOSCOPY IS A SAFE TEST IN CARDIAC TRANSPLANT CANDIDATES. David T. Rubin, Taimur Habib. Waqas Ali, Linda Tutzauer, Allen Anderson, Univ of Chicago, Chicago, IL. Background: The presence of an occult malignancy is an absolute contraindication for cardiac transplantation, so pre-transplant work-Up involves routine screening tests. Although colonoscopy is a preferred screening tool for colorectal cancer, its safety in patients with serious chronic heart disease remains a concern. Aim: To review the safety of colonoscopy in our pre-cardiac transplant patient population. Methods:Patients over the age of 50 who were being evaluated for cardiac transplantation and had colonoscopies were identified. Pre-colonoscopy New York Heart Association (NYHA) class and anti-coagulation status were reviewed.Warfarin or aspirin were discontinued one week prior to planned colonoscopy. Standard electrocardiograpic, blood pressure, and pulse oximetry monitoring were performed throughout the procedure. Complications from the colonoscopy, the sedation and analgesia. or the alteration in anticoagulation were reviewed. Results: Six patients (mean age 60 yrs, range 52-67) had colonoscopy for the following indications: screening (2), anemia (3), and heme positive stool (I) . Patients had ischemic dilated cardiomyopathy (3), idiopathic dilated cardiomyopathy (2), and acromegaly (I), and were either using warfarin (2), aspirin (2), or no anticoagulation (2). NYHA classes were III in 5 patients and II in one patient. Midazolam (mean 2 mg IV)and meperidine (median 75 mg IV) sedation and analgesia were administered to all patients. One patient (NYHA III) required naloxone due to hypoventilation after receiving 75 mg of meperidine, and recovered uneventfully. There were no other cardiopulmonary complications. Five colonoscopies reached the cecum, and one was discontinued due to diverticular disease and an inability to pass the colonoscope. Three patients had normal exams, two patients had hemorrhoidsand diverticular disease, one patient had a non-bleeding vascular malformation in the cecum, and one patient had a 5 mm polyp in the rectum which was not removed. There were no bleeding or thrombotic complications before, during, or after the procedures. No colonic perforations occurred. Conclusion: Colonoscopy with routine hemodynamic monitoring can be performed safely during pre-cardiac transplant work-up in patients with NYHA class III disease. Colorectal cancer screening should not be avoided in similar patients with chronic heart disease.
April 2000
6398 DIFFERENTIAL EXPRESSION OF LEPTIN IN LIPOMATOUS AND NON·LIPOMOTAOUS SOFT TISSUE TUMORS. U. Ritzel, U. Brinck, U. Leonhardt, L. Fuezesi, G. Ramadori, Univ of Goettingen, Goettingen, Germany. INTRODUCTION: Recent evidence suggest that within mesenchymal tissues leptin, a proteohonnone, is exclusively secreted by adipocytes. The main aim of the present study was to analyse the expression of leptin in lipomatous and non-lipomatous tumors. METHODS: 35 cases of lipomatous tumors (6 lipomas, 17 low grade liposarcomas, 12 liposarcomas of grade II and III), and 18 cases of non-lipomatous soft tissue sarcomas (12 MFH, 4 pleomorphic leiomyosarcomas,2 embryonic rhabdomyosarcomas) were stained immunohistochemically for the presence of leptin. One lipoma, a well differenciated and a round cell liposarcoma, were additionally analysed for the presence of leptin mRNA transcripts by RT-PCR. RESULTS: Leptin protein expression was found in all lipomas, 15/17 low grade liposarcomas, including 7 well differenciated and 8 myxoid liposarcomas, 5/12 liposarcomas of grade II and III, including round cell and pleomorphic liposarcomas, and in one of the non-lipomatous sarcomas. Leptin mRNA transcripts were present in all 3 investigated lipomatous tumors. CONCLUSIONS: Leptin is differentially expressed in lipomatous tumors and non-lipomatous sarcomas with fibrohistiocytic and muscle differentiation. Detection of leptin expression in myxoid, round cell, and pleomorphic sarcomas may be helpful to support the histopathological diagnosis of liposarcoma. 6399 PEPTIDE YY AUGMENTS THE INHIBITORY EFFECTS OF AL· PHA·TOCOPHEROL SUCCINATE ON PROSTATE CANCER CELL GROWTH. Amy T. Rose, Tracy Heisler, Shirin Towfigh, Natalie Simon, David W. McFadden, UCLA, Los Angeles, CA. Alpha-tocopherol succinate (ATS) has been shown to induce apoptosis of hormone-refractoryprostate cancer cells in vitro and inhibit cell growth in vivo. Peptide YY (PYY) has growth inhibitory activity against multiple cancer cell lines and is synergistic with ATS against breast cancer cells. No data exists on the impact of PYY and ATS against prostate cancer cell lines, cells similar to breast cancer in their hormonal regulation. Methods: A hormone-refractory human prostate cancer cell line, PC-3, was treated with ATS alone at doses ranging from 10 to 100 mcg/cc, PYY alone at doses of 50 to 500 pmol, or a combination of the two agents. MTT assay was performedat 24, 48, and 72 hours to determinecell viability. Statistical analysis was performed with the Student's t-test. Results: Both ATS and PYY exhibited a growth inhibitory effect on the prostate cancer cells compared to controls. ATS caused decreased cell viability with 50 or 100 mcg/cc by 24 hours (p
cell lines. Further work needs to be initiated to further characterize the mechanism of the growth inhibitory effects of PYY.
Percentage of Cells per Phase of Cell Cycle Untreated
Treated
pvalue 0.308 0.432 0,338
GO-G1
71.35
72,09
S
16.82
16,55
G2·M
11 .84
11 ,37
6401 MICROSATELLITE INSTABILITY IN INFLAMMATORY BOWEL DISEASE. Valentina Rovella, Marcello Anti, Maurizio Genuardi, Fabio M. Vecchio. Sandro Rinelli, Alfredo Pastorelli, Antonio Gasbarrini, Giovanni Neri, Giovanni Gasbarrini, Catholic Univ of Rome; Catholic Univ of Rome, Rome, Italy; Institute of Med Genetics, Catholic Univ of Rome, Rome, Italy; Italy. Long-standing Inflammatory Bowel Disease (18D) is a condition at increased colon cancer risk. Mutation or "instability" of microsatellite DNA sequences (MSI) are markers for mutation of genes which are involved in the DNA mismatch repair (MMR)system. MSI has previously reported in non cancerous mucosa of patients with Ulcerative Colitis (UC) and it has been speculated that this finding may be due to an oversaturation of MMR system associated to an increase of epithelial cell proliferation, caused by chronic inflammation. METHODS: In this study we analized five microsatellite markers (02S123, BAT-26, BAT-25, IGFIIR, TGFf3IIR) in biopsy samples taken from 20 patients with UC and 4 patients with Crohn's Disease (CD). Clinical activity, endoscopic and histological scores, degree of inflammationand the presence or absence of high-grade dysplasia were recorded for each patient. RESULTS: Frameshift mutation in the poly(A)IO tract of BAT-26 was found in only one case of CD. Tissue in which MSI was observed had been taken from the right-colon; no dysplasia was found and only a moderate inflammation was present in the sample. No MSI was detected in other colonic areas of the same patient. CONCLUSIONS: In contrast with previous reports, MSI was very rare in this series of patients with IBD. However the detection of MSI in non dysplastic mucosa and in absence of intense inflammation , raises the question whether MSI can be used as an early predictor marker for colon cancer risk. 6402 COLONOSCOPY IS A SAFE TEST IN CARDIAC TRANSPLANT CANDIDATES. David T. Rubin, Taimur Habib. Waqas Ali, Linda Tutzauer, Allen Anderson, Univ of Chicago, Chicago, IL. Background: The presence of an occult malignancy is an absolute contraindication for cardiac transplantation, so pre-transplant work-Up involves routine screening tests. Although colonoscopy is a preferred screening tool for colorectal cancer, its safety in patients with serious chronic heart disease remains a concern. Aim: To review the safety of colonoscopy in our pre-cardiac transplant patient population. Methods:Patients over the age of 50 who were being evaluated for cardiac transplantation and had colonoscopies were identified. Pre-colonoscopy New York Heart Association (NYHA) class and anti-coagulation status were reviewed.Warfarin or aspirin were discontinued one week prior to planned colonoscopy. Standard electrocardiograpic, blood pressure, and pulse oximetry monitoring were performed throughout the procedure. Complications from the colonoscopy, the sedation and analgesia. or the alteration in anticoagulation were reviewed. Results: Six patients (mean age 60 yrs, range 52-67) had colonoscopy for the following indications: screening (2), anemia (3), and heme positive stool (I) . Patients had ischemic dilated cardiomyopathy (3), idiopathic dilated cardiomyopathy (2), and acromegaly (I), and were either using warfarin (2), aspirin (2), or no anticoagulation (2). NYHA classes were III in 5 patients and II in one patient. Midazolam (mean 2 mg IV)and meperidine (median 75 mg IV) sedation and analgesia were administered to all patients. One patient (NYHA III) required naloxone due to hypoventilation after receiving 75 mg of meperidine, and recovered uneventfully. There were no other cardiopulmonary complications. Five colonoscopies reached the cecum, and one was discontinued due to diverticular disease and an inability to pass the colonoscope. Three patients had normal exams, two patients had hemorrhoidsand diverticular disease, one patient had a non-bleeding vascular malformation in the cecum, and one patient had a 5 mm polyp in the rectum which was not removed. There were no bleeding or thrombotic complications before, during, or after the procedures. No colonic perforations occurred. Conclusion: Colonoscopy with routine hemodynamic monitoring can be performed safely during pre-cardiac transplant work-up in patients with NYHA class III disease. Colorectal cancer screening should not be avoided in similar patients with chronic heart disease.