The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Richard L Whelan - One of the best experts on this subject based on the ideXlab platform.
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higher colon cancer tumor Proliferative Index and lower tumor cell death rate in mice undergoing laparotomy versus insufflation
Surgical Endoscopy and Other Interventional Techniques, 2002Co-Authors: Sang W Lee, N R Gleason, I Blanco, Z K Asi, Richard L WhelanAbstract:Background: Our laboratory has previously shown that tumors are established more easily and grow larger after laparotomy than after laparoscopy. To characterize these differences in tumor growth further, the tumor cell death rates and tumor proliferation rates were compared in vivo after full sham laparotomy versus carbon dioxide (CO 2 ) insufflation. Methods: Female Balb/C mice (n = 36) were inoculated intradermally in the dorsal skin with 10 6 C-26 colon adenocarcinoma cells in 0.1 ml of culture media no more than 1 h before interventions. The mice then were randomized to one of three groups: anesthesia control, CO 2 insufflation, or sham laparotomy. The anesthesia control group underwent no procedure. The insufflation group underwent CO 2 pneumoperitoneum (4-6 mmHg) for 20 min via a 20-gauge angiocatheter. The laparotomy group underwent a midline incision from xiphoid to pubis, which was closed after 20 min. Tumors were excised from half the mice in each group on postoperative day 7, and from the remaining mice on post-operative day 14. Sections of tumors were made then stained separately for free 3' hydroxyl ends of genomic deoxyribonucleic acid (DNA) using fluorescein-deoxyunidine triphosphate (dUTP), and immunohistochemically for proliferating cell nuclear antigen (PCNA). Apoptosis was measured by quantitating DNA strand breaks in individual cells using fluorescence microscopy. Fluorescein-positive cells in five random high-power fields (x200) were counted in a blinded fashion. The Proliferative Index of each tumor was determined by averaging PCNA positive cells in five high-power fields (x450) counted in a blinded fashion with the aid of an optical grid. Results: On postoperative day 7, there was no significant difference in the Proliferative Index or apoptotic rates among the three groups. On postoperative day 14, the Proliferative Index in the laparotomy group was significantly higher than in either the insufflation or control group (p < 0.001). The Proliferative Index in the insufflation group also was significantly higher than in the control group (p < 0.05). Inverse differences in apoptotic rates were found. The apoptotic rate in the laparotomy group was significantly lower than in either the insufflation (p < 0.05) or control group (p < 0.001). The apoptotic rate in the insufflation group was significantly lower than in the control group (p < 0.001). Conclusions: We have demonstrated that there is a significantly higher rate of tumor cell proliferation and a significantly lower rate of tumor cell death with the C-26 colon adenocarcinoma tumor line after laparotomy than after insufflation or anesthesia alone on post-operative day 14. The mechanisms of these phenomena are unclear. It appears that certain factors postoperatively stimulate tumors to proliferate at a higher rate, causing tumor cells to die at a lower rate in the laparotomy group than in the insufflation group.
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tumor Proliferative Index is higher in mice undergoing laparotomy vs co2 pneumoperitoneum
Diseases of The Colon & Rectum, 1999Co-Authors: Sang W Lee, John C Southall, John D Allendorf, Marc Bessler, Richard L WhelanAbstract:PURPOSE: Our laboratory has previously shown that tumors are more easily established and grow larger after laparotomyvs. laparoscopy. The purpose of this study was to better characterize these differences in tumor growth by assessing tumor cell proliferationvia the proliferating cell nuclear antigen assay, which has been shown to be a reliable marker of cellular proliferation. METHODS: Female C3H/He mice (N=40) were inoculated intradermally in the dorsal skin with 106 cultured mouse mammary carcinoma cells <1 hour before interventions. Anesthesia control mice underwent no procedure. Laparotomy group mice had a midline incision from xiphoid to pubis that was closed after 20 minutes. Insufflation group mice underwent CO2 pneumoperitoneum (4–6 mmHg) for 20 minutes. On postoperative Day 6, tumors were excised from one-third of the mice in each group, and from the remaining mice on postoperative Day 12. Sections were made and stained immunohistochemically for proliferating cell nuclear antigen, and the Proliferative Index of each tumor was determined by taking the average of proliferating cell nuclear antigen-positive cells in five high-power fields (×450), counted in a blinded fashion with the aid of an optical grid. RESULTS: On postoperative Day 6, the mean Proliferative Index for the laparotomy group was significantly higher than those for both the insufflation (P<0.04) and the control (P<0.001) groups. Of note, the Proliferative Index of the insufflation group was significantly higher than that of the control (P<0.01) group. Similarly, on postoperative Day 12, the mean Proliferative Index for the laparotomy group was significantly higher than for both the insufflation (P<0.05) and the control (P<0.005)groups. The Proliferative Index in the insufflation group was also significantly higher than that of the control (P<0.04) group. CONCLUSIONS: We have demonstrated that there is a significantly higher rate of tumor cell proliferation with the mouse mammary carcinoma cell tumor line after laparotomy than after pneumoperitoneum or anesthesia alone at two postoperative times. Additionally, insufflation alone increases postoperative tumor cell proliferation but to a lesser extent than laparotomy. The mechanism underlying these findings is unclear.
Andrew D Zelenetz - One of the best experts on this subject based on the ideXlab platform.
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prognostic impact of Proliferative Index determined by quantitative image analysis and the international prognostic Index in patients with mantle cell lymphoma
Annals of Oncology, 2010Co-Authors: R Schaffel, Carol S Portlock, Cyrus V Hedvat, Daniel O Persky, Jocelyn C Maragulia, Julie Teruyafeldstein, Craig H Moskowitz, Andrew D ZelenetzAbstract:Background: The Proliferative Index (PI) is a powerful prognostic factor in mantle cell lymphoma (MCL); however, its utility is hampered by interobserver variability. The mantle cell international prognostic Index (MIPI) has been reported to have prognostic importance. In this study, we determined the prognostic value of the PI as determined by quantitative image analysis in MCL. Patients and methods: Eighty-eight patients with adequate tissue were included in this analysis. Patients were treated with one of two treatment programs: sequential therapy with high-dose therapy consolidation or radioimmunotherapy followed by combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone. Patients were divided into four groups based on PI ( 50%), and outcomes were analyzed. Results: Thirty percent was identified as the optimal cut-off for PI. By univariate analysis, intensive treatment and a low PI were associated with a superior progression-free survival (PFS); only PI was associated with overall survival. By multivariate analysis, both intensive treatment and PI correlated with PFS. The MIPI had no prognostic impact. Conclusions: PI is the most important prognostic factor in MCL. The cut-off of 30% is clinically meaningful and can be used to tailor the intensity of therapy in future clinical trials.
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prognostic impact of Proliferative Index determined by quantitative image analysis and the international prognostic Index in patients with mantle cell lymphoma
Annals of Oncology, 2010Co-Authors: R Schaffel, Carol S Portlock, Cyrus V Hedvat, Daniel O Persky, Jocelyn C Maragulia, Julie Teruyafeldstein, Craig H Moskowitz, Andrew D ZelenetzAbstract:Background: The Proliferative Index (PI) is a powerful prognostic factor in mantle cell lymphoma (MCL); however, its utility is hampered by interobserver variability. The mantle cell international prognostic Index (MIPI) has been reported to have prognostic importance. In this study, we determined the prognostic value of the PI as determined by quantitative image analysis in MCL. Patients and methods: Eighty-eight patients with adequate tissue were included in this analysis. Patients were treated with one of two treatment programs: sequential therapy with high-dose therapy consolidation or radioimmunotherapy followed by combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone. Patients were divided into four groups based on PI ( 50%), and outcomes were analyzed. Results: Thirty percent was identified as the optimal cut-off for PI. By univariate analysis, intensive treatment and a low PI were associated with a superior progression-free survival (PFS); only PI was associated with overall survival. By multivariate analysis, both intensive treatment and PI correlated with PFS. The MIPI had no prognostic impact. Conclusions: PI is the most important prognostic factor in MCL. The cut-off of 30% is clinically meaningful and can be used to tailor the intensity of therapy in future clinical trials.
Dorian R A Swarts - One of the best experts on this subject based on the ideXlab platform.
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limited additive value of the ki 67 Proliferative Index on patient survival in world health organization classified pulmonary carcinoids
Histopathology, 2017Co-Authors: Dorian R A Swarts, Martina Rudelius, Sandra M H Claessen, Jack P M Cleutjens, Stefan Seidl, Marco Volante, Frans C S Ramaekers, Ernst J M SpeelAbstract:Aims Currently pulmonary carcinoids are separated into typical (TC) and atypical (AC) based on mitotic count and presence of necrosis, according to the WHO. At variance with gastroenteropancreatic neuroendocrine tumors, which are graded based on mitotic count and Ki-67 Proliferative Index, the use of Ki-67 for grading pulmonary carcinoids is still under debate. Methods and results In this study we evaluated the prognostic impact of Ki-67 assessment in a multicenter cohort of 201 carcinoids (147 TCs, 54 ACs), using manual analysis (2000 cells counted) and digital image analysis (in-house Leica Qwin program; ≥ 4500 cells counted). The Ki-67 Proliferative Index was correlated with overall survival by means of univariate analysis and in comparison to clinical data by means of multivariable analysis. The Ki-67 Index was significantly higher in ACs than in TCs for both counting methods (P ≤ 2.7e−5). In addition, using cut-offs of 2.5% and 4% (manual counting) or 1% and 5% (digital analysis), the highest differences in overall survival were observed (P ≤ 0.0067). Nevertheless, histopathological classification into TCs and ACs showed an equally strong association with disease outcome, although within TCs Ki-67 had some additive value. Ki-67 Index was not an independent predictor of survival in multivariable analysis. Conclusions Our study demonstrates that, although Ki-67 is a strong prognostic factor for pulmonary carcinoids, its usefulness in addition to histopathology in prediction of prognosis is limited. Nonetheless, it may have additional value, especially in cases that are difficult to classify, in combination with histopathology and other molecular markers. This article is protected by copyright. All rights reserved.
James Kubus - One of the best experts on this subject based on the ideXlab platform.
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comparative analysis of the nuclear Proliferative Index ki 67 in benign prostate prostatic intraepithelial neoplasia and prostatic carcinoma
Modern Pathology, 1996Co-Authors: Pheroze Tamboli, Mahul B Amin, Daniel Schultz, Michael Linden, James KubusAbstract:High-grade prostatic intraepithelial neoplasia (HG-PIN) lies in the morphologic continuum between benign and carcinomatous prostate, but its status as a neoplastic precursor remains only putative. We measured nuclear Proliferative activity using MIB-1 antibody to further characterize the cell kinetics of HG-PIN and to assess its relationship to prostatic adenocarcinoma. We studied 36 specimens from randomly selected patients who underwent radical prostatectomies for prostatic adenocarcinoma. Sections of formalin-fixed, paraffin-embedded tissue pretreated by a citric acid monohydrate antigen retrieval method were immunostained with the mouse monoclonal antibody MIB-1, which detects the Ki-67 antigen in formalin-fixed tissue. The Ki-67 antigen is expressed by non-G0 proliferating cells and has been used to assess cellular Proliferative activity. A maximum of either 20,400 x fields or 100 positively stained nuclei in benign glands, areas of HG-PIN, and adenocarcinoma were counted to obtain an immunohistologic proliferation Index for each case. For benign prostate, HG-PIN, and adenocarcinoma, the mean positivity was 0.4 +/- 0.42 cells per field (range, 0-2), 2.5 +/- 3.79 cells per field (range, 0-16.6), and 13.8 +/- 15.05 cells per field (range, 0.25-73.66), respectively. Using a Kruskall-Wallis analysis of variance (chi 2 = 58, P < 0.05) and the t test for dependent samples, we found that the mean Ki-67 antigen expression significantly differs between histologic categories (P < 0.01, all three comparisons). In addition, the Proliferative Index consistently increased along the continuum from benign to malignant. We conclude that the MIB-1 Proliferative Index of HG-PIN lies between that of benign and carcinomatous prostate, supporting the assertion that HG-PIN is a biologic intermediate in the multistep process of transformation into carcinoma.
Sang W Lee - One of the best experts on this subject based on the ideXlab platform.
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higher colon cancer tumor Proliferative Index and lower tumor cell death rate in mice undergoing laparotomy versus insufflation
Surgical Endoscopy and Other Interventional Techniques, 2002Co-Authors: Sang W Lee, N R Gleason, I Blanco, Z K Asi, Richard L WhelanAbstract:Background: Our laboratory has previously shown that tumors are established more easily and grow larger after laparotomy than after laparoscopy. To characterize these differences in tumor growth further, the tumor cell death rates and tumor proliferation rates were compared in vivo after full sham laparotomy versus carbon dioxide (CO 2 ) insufflation. Methods: Female Balb/C mice (n = 36) were inoculated intradermally in the dorsal skin with 10 6 C-26 colon adenocarcinoma cells in 0.1 ml of culture media no more than 1 h before interventions. The mice then were randomized to one of three groups: anesthesia control, CO 2 insufflation, or sham laparotomy. The anesthesia control group underwent no procedure. The insufflation group underwent CO 2 pneumoperitoneum (4-6 mmHg) for 20 min via a 20-gauge angiocatheter. The laparotomy group underwent a midline incision from xiphoid to pubis, which was closed after 20 min. Tumors were excised from half the mice in each group on postoperative day 7, and from the remaining mice on post-operative day 14. Sections of tumors were made then stained separately for free 3' hydroxyl ends of genomic deoxyribonucleic acid (DNA) using fluorescein-deoxyunidine triphosphate (dUTP), and immunohistochemically for proliferating cell nuclear antigen (PCNA). Apoptosis was measured by quantitating DNA strand breaks in individual cells using fluorescence microscopy. Fluorescein-positive cells in five random high-power fields (x200) were counted in a blinded fashion. The Proliferative Index of each tumor was determined by averaging PCNA positive cells in five high-power fields (x450) counted in a blinded fashion with the aid of an optical grid. Results: On postoperative day 7, there was no significant difference in the Proliferative Index or apoptotic rates among the three groups. On postoperative day 14, the Proliferative Index in the laparotomy group was significantly higher than in either the insufflation or control group (p < 0.001). The Proliferative Index in the insufflation group also was significantly higher than in the control group (p < 0.05). Inverse differences in apoptotic rates were found. The apoptotic rate in the laparotomy group was significantly lower than in either the insufflation (p < 0.05) or control group (p < 0.001). The apoptotic rate in the insufflation group was significantly lower than in the control group (p < 0.001). Conclusions: We have demonstrated that there is a significantly higher rate of tumor cell proliferation and a significantly lower rate of tumor cell death with the C-26 colon adenocarcinoma tumor line after laparotomy than after insufflation or anesthesia alone on post-operative day 14. The mechanisms of these phenomena are unclear. It appears that certain factors postoperatively stimulate tumors to proliferate at a higher rate, causing tumor cells to die at a lower rate in the laparotomy group than in the insufflation group.
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tumor Proliferative Index is higher in mice undergoing laparotomy vs co2 pneumoperitoneum
Diseases of The Colon & Rectum, 1999Co-Authors: Sang W Lee, John C Southall, John D Allendorf, Marc Bessler, Richard L WhelanAbstract:PURPOSE: Our laboratory has previously shown that tumors are more easily established and grow larger after laparotomyvs. laparoscopy. The purpose of this study was to better characterize these differences in tumor growth by assessing tumor cell proliferationvia the proliferating cell nuclear antigen assay, which has been shown to be a reliable marker of cellular proliferation. METHODS: Female C3H/He mice (N=40) were inoculated intradermally in the dorsal skin with 106 cultured mouse mammary carcinoma cells <1 hour before interventions. Anesthesia control mice underwent no procedure. Laparotomy group mice had a midline incision from xiphoid to pubis that was closed after 20 minutes. Insufflation group mice underwent CO2 pneumoperitoneum (4–6 mmHg) for 20 minutes. On postoperative Day 6, tumors were excised from one-third of the mice in each group, and from the remaining mice on postoperative Day 12. Sections were made and stained immunohistochemically for proliferating cell nuclear antigen, and the Proliferative Index of each tumor was determined by taking the average of proliferating cell nuclear antigen-positive cells in five high-power fields (×450), counted in a blinded fashion with the aid of an optical grid. RESULTS: On postoperative Day 6, the mean Proliferative Index for the laparotomy group was significantly higher than those for both the insufflation (P<0.04) and the control (P<0.001) groups. Of note, the Proliferative Index of the insufflation group was significantly higher than that of the control (P<0.01) group. Similarly, on postoperative Day 12, the mean Proliferative Index for the laparotomy group was significantly higher than for both the insufflation (P<0.05) and the control (P<0.005)groups. The Proliferative Index in the insufflation group was also significantly higher than that of the control (P<0.04) group. CONCLUSIONS: We have demonstrated that there is a significantly higher rate of tumor cell proliferation with the mouse mammary carcinoma cell tumor line after laparotomy than after pneumoperitoneum or anesthesia alone at two postoperative times. Additionally, insufflation alone increases postoperative tumor cell proliferation but to a lesser extent than laparotomy. The mechanism underlying these findings is unclear.
