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Title: Jurnal Medical Aradean (Arad Medical Journal)
Abbreviated title: J. Med. Ar.
Publisher: "Vasile Goldis" University Press
Owner: Western University "Vasile Goldis" Arad, Romania
ISSN: 1224-3744
e-ISSN: 2067-7790

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THE PROGNOSTIC ROLE OF MAST CELLS ACCORDING WITH THE HISTOLOGICAL GROWTH PATTERN IN LIVER METASTASIS OF TUMORS WITH DIGESTIVE ORIGINS PDF Print E-mail

THE PROGNOSTIC ROLE OF MAST CELLS ACCORDING WITH THE HISTOLOGICAL GROWTH PATTERN IN LIVER METASTASIS OF TUMORS WITH DIGESTIVE ORIGINS

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Title: THE PROGNOSTIC ROLE OF MAST CELLS ACCORDING WITH THE HISTOLOGICAL GROWTH PATTERN IN LIVER METASTASIS OF TUMORS WITH DIGESTIVE ORIGINS
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Article_Title: THE PROGNOSTIC ROLE OF MAST CELLS ACCORDING WITH THE HISTOLOGICAL GROWTH PATTERN IN LIVER METASTASIS OF TUMORS WITH DIGESTIVE ORIGINS
Authors: 1,2Ciolofan A, 2*Ceausu AR, 2Gaje NP, 2Tudor AM, 1Cretu O , 3Nicolescu A
Affiliation: 1”Victor Babes” University of Medicine and Pharmacy, Department of Surgery, Timisoara, Romania,
2 “Victor Babes” University of Medicine and Pharmacy, Department of Microscopic Morphology/ Histology, Angiogenesis Research Center Timisoara, Romania,
3„Vasile Goldis” Western University of Arad, Romania, Department of Intensive Care.
Abstract: Despite the significant progress regarding molecular classifications for colon, pancreatic and gastric cancer, the therapeutic methods (arterial, chimio and radioembolization), the life expectancy of patients with existing liver metastases did not improve significantly. The aim was to analyze the interrelation between the vascularization, mast cells and the histological growth pattern of hepatic metastasis with digestive origins. 25 patients were evaluated by ways of the immunohistochemical technique. The distribution of the liver metastasis growth pattern was as follows: colon (all 3 types), pancreatic (replacement), gastric (pushing type). A significant correlation between mast cell density in the peritumoral area and vascular microdensity in the metastatic domain of all histological growth patterns was found. Significant correlation between positive mast cells tryptase density and degree of differentiation for the desmoplastic type was noticed. The mast cells may have a prognostic role in this growth pattern and the mast cell inhibitor therapy may be useful.
Keywords: mast cells, liver metastasis, histological growth pattern
References: 1. Terayama N, Terada T, Nakanuma Y. Histologic growth patterns of metastatic carcinomas of the liver. Jpn J Clin Oncol; 26: 24–29, 1996.
2. Vermeulen PB, Colpaert C, Salgado R, Royers R, Hellemans H, Van Den Heuvel E, et al. Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia. J Pathol;195: 336–342, 2001.
3. Negru Ş: Oncologie generală. Editura Victor Babeş, 2011. Capitolul 6: Invazia locală şi metastazarea, pag 28-30.
4. Hodges K, Kennedy L, Meng F, et al. Mast cells, disease and gastrointestinal cancer: A comprehensive review of recent findings. Translational gastrointestinal cancer. 2012;1(2):138-150.
5. Ammendola M, Marech I, Sammarco G, et al. Infiltrating Mast Cells Correlate with Angiogenesis in Bone Metastases from Gastric Cancer Patients. Int J Mol Sci. 2015, 16, 3237-3250.
6. Suzuki S, Ichikawa Y, Nakagawa K, et al. High infiltration of mast cells positive to tryptase predicts worse outcome following resection of colorectal liver metastases. BMC Cancer. 2015;15:840.
7. Giuşcă SE, Căruntu ID, Cîmpean AM, et al. Tryptase-positive and CD117 Positive Mast Cells Correlate with Survival in Patients with Liver Metastasis. Anticancer Res. 2015 Oct;35(10):5325-31.
8. Weidner N, Measuring intratumoral microvessel density. Methods Enzymol; 444:305-323, 2008.
9. Van den Eynden GG, Bird NC, Majeed AW, et al. The histological growth pattern of colorectal cancer liver metastases has prognostic value. Clin Exp Metastasis. 2012 Aug;29(6):541-9.
10. Clark AM, Wheeler SE, Taylor DP, et al. A microphysiological system model of therapy for liver micrometastases. Exp Biol Med. 239(9):1170-1179.
11. Lazar D, Raica M, Sporea I, et al. Tumor angiogenesis in gastric cancer. Rom J Morphol Embryol. 2006, 47, 5–13.
12. Nakae S, Suto H, Kakurai M, et al. Mast cells enhance T cell activation: Importance of mast cell-derived TNF. Proc Natl Acad Sci USA. 2005, 102, 6467–6472.
13. Ribatti D, Ranieri G, Nico B, et al. Tryptase and chymase are angiogenic in vivo in the chorioallantoic membrane assay. Int J Dev Biol. 2011, 55, 99–102.
14. Gruber BL, Marchese MJ, Suzuki K, et al. Synovial procollagenase activation by human mast cell tryptase dependence up on matrixmetallo-proteinase 3 activation. J Clin Investig. 1989, 84, 1657–1662.
15. Khazaie K, Blatner NR, Khan MW, et al. The significant role of mast cells in cancer. Cancer Metastasis Rev. 2011, 30, 45–60.
16. Mukherjee S, Bandyopadhyay G, Dutta D, et al. Evaluation of endoscopic biopsy in gastric lesions with a special reference to the significance of mast cell density. Indian J Pathol Microbiol. 2009, 52, 20–24.
17. Ammendola M, Leporini C, Marech I, et al. Targeting mast cells tryptase in tumor microenvironment: A potential antiangiogenetic strategy. Biomed Res Int. 2014, 2014, 154702.
18. Blair RJ, Meng H, Marchese MJ, et al. Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor. J Clin Investig. 1997, 99, 2691–2700.
19. Ribatti D, Guidolin D, Marzullo A, et al. Mast cells and angiogenesis in gastric carcinoma. Int J Exp Pathol. 2010, 91: 350–356.
20. Morris DR, Ding Y, Ricks TK, et al. Protease-activated receptor-2 is essential for factor VIIa and Xa-induced signaling, migration, and invasion of breast cancer cells. Cancer Res. 2006, 66, 307–314.
21. Soucek L, Lawlor ER, Soto D, et al. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nature Medicine, vol. 13, no. 10, pp. 1211–1218, 2007.
Read_full_article: pdf/vol20/iss1/1 JMA  - Ciolofan.pdf
Correspondence: • CIOLOFAN ALEXANDRU, MD, PhD student
”Victor Babes” University of Medicine and Pharmacy, Department of Surgery
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 004025620447
• CEAUSU AMALIA RALUCA*, MD, PhD, Lecturer
”Victor Babes” University of Medicine and Pharmacy, Department of Microscopic Morphology/ Histology, Angiogenesis Research Center, Timisoara
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 0040740872707
e-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it
• GAJE NELA PUSA, MD, PhD, Associate Professor
”Victor Babes” University of Medicine and Pharmacy, Department of Microscopic Morphology/ Histology, Angiogenesis Research Center Timisoara
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 0040256204476
• TUDOR ADELINA MARIA, student
”Victor Babes” University of Medicine and Pharmacy, Department of Microscopic Morphology/ Histology, Angiogenesis Research Center Timisoara
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 0040256204476
• CRETU OCTAVIAN, MD, PhD, Professor
”Victor Babes” University of Medicine and Pharmacy, Department of Surgery
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 0040256204476
• NICOLESCU AMALIA, MD, PhD, Teaching Assistant
„Vasile Goldis” Western University of Arad, Romania, Department of Intensive Care
No.86 Liviu Rebreanu Street, 310045, Arad, Romania, Phone: +40-257-212204
Read full article
Article Title: THE PROGNOSTIC ROLE OF MAST CELLS ACCORDING WITH THE HISTOLOGICAL GROWTH PATTERN IN LIVER METASTASIS OF TUMORS WITH DIGESTIVE ORIGINS
Authors: 1,2Ciolofan A, 2*Ceausu AR, 2Gaje NP, 2Tudor AM, 1Cretu O , 3Nicolescu A
Affiliation: 1”Victor Babes” University of Medicine and Pharmacy, Department of Surgery, Timisoara, Romania,
2 “Victor Babes” University of Medicine and Pharmacy, Department of Microscopic Morphology/ Histology, Angiogenesis Research Center Timisoara, Romania,
3„Vasile Goldis” Western University of Arad, Romania, Department of Intensive Care.
Abstract: Despite the significant progress regarding molecular classifications for colon, pancreatic and gastric cancer, the therapeutic methods (arterial, chimio and radioembolization), the life expectancy of patients with existing liver metastases did not improve significantly. The aim was to analyze the interrelation between the vascularization, mast cells and the histological growth pattern of hepatic metastasis with digestive origins. 25 patients were evaluated by ways of the immunohistochemical technique. The distribution of the liver metastasis growth pattern was as follows: colon (all 3 types), pancreatic (replacement), gastric (pushing type). A significant correlation between mast cell density in the peritumoral area and vascular microdensity in the metastatic domain of all histological growth patterns was found. Significant correlation between positive mast cells tryptase density and degree of differentiation for the desmoplastic type was noticed. The mast cells may have a prognostic role in this growth pattern and the mast cell inhibitor therapy may be useful.
Keywords: mast cells, liver metastasis, histological growth pattern
References: 1. Terayama N, Terada T, Nakanuma Y. Histologic growth patterns of metastatic carcinomas of the liver. Jpn J Clin Oncol; 26: 24–29, 1996.
2. Vermeulen PB, Colpaert C, Salgado R, Royers R, Hellemans H, Van Den Heuvel E, et al. Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia. J Pathol;195: 336–342, 2001.
3. Negru Ş: Oncologie generală. Editura Victor Babeş, 2011. Capitolul 6: Invazia locală şi metastazarea, pag 28-30.
4. Hodges K, Kennedy L, Meng F, et al. Mast cells, disease and gastrointestinal cancer: A comprehensive review of recent findings. Translational gastrointestinal cancer. 2012;1(2):138-150.
5. Ammendola M, Marech I, Sammarco G, et al. Infiltrating Mast Cells Correlate with Angiogenesis in Bone Metastases from Gastric Cancer Patients. Int J Mol Sci. 2015, 16, 3237-3250.
6. Suzuki S, Ichikawa Y, Nakagawa K, et al. High infiltration of mast cells positive to tryptase predicts worse outcome following resection of colorectal liver metastases. BMC Cancer. 2015;15:840.
7. Giuşcă SE, Căruntu ID, Cîmpean AM, et al. Tryptase-positive and CD117 Positive Mast Cells Correlate with Survival in Patients with Liver Metastasis. Anticancer Res. 2015 Oct;35(10):5325-31.
8. Weidner N, Measuring intratumoral microvessel density. Methods Enzymol; 444:305-323, 2008.
9. Van den Eynden GG, Bird NC, Majeed AW, et al. The histological growth pattern of colorectal cancer liver metastases has prognostic value. Clin Exp Metastasis. 2012 Aug;29(6):541-9.
10. Clark AM, Wheeler SE, Taylor DP, et al. A microphysiological system model of therapy for liver micrometastases. Exp Biol Med. 239(9):1170-1179.
11. Lazar D, Raica M, Sporea I, et al. Tumor angiogenesis in gastric cancer. Rom J Morphol Embryol. 2006, 47, 5–13.
12. Nakae S, Suto H, Kakurai M, et al. Mast cells enhance T cell activation: Importance of mast cell-derived TNF. Proc Natl Acad Sci USA. 2005, 102, 6467–6472.
13. Ribatti D, Ranieri G, Nico B, et al. Tryptase and chymase are angiogenic in vivo in the chorioallantoic membrane assay. Int J Dev Biol. 2011, 55, 99–102.
14. Gruber BL, Marchese MJ, Suzuki K, et al. Synovial procollagenase activation by human mast cell tryptase dependence up on matrixmetallo-proteinase 3 activation. J Clin Investig. 1989, 84, 1657–1662.
15. Khazaie K, Blatner NR, Khan MW, et al. The significant role of mast cells in cancer. Cancer Metastasis Rev. 2011, 30, 45–60.
16. Mukherjee S, Bandyopadhyay G, Dutta D, et al. Evaluation of endoscopic biopsy in gastric lesions with a special reference to the significance of mast cell density. Indian J Pathol Microbiol. 2009, 52, 20–24.
17. Ammendola M, Leporini C, Marech I, et al. Targeting mast cells tryptase in tumor microenvironment: A potential antiangiogenetic strategy. Biomed Res Int. 2014, 2014, 154702.
18. Blair RJ, Meng H, Marchese MJ, et al. Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor. J Clin Investig. 1997, 99, 2691–2700.
19. Ribatti D, Guidolin D, Marzullo A, et al. Mast cells and angiogenesis in gastric carcinoma. Int J Exp Pathol. 2010, 91: 350–356.
20. Morris DR, Ding Y, Ricks TK, et al. Protease-activated receptor-2 is essential for factor VIIa and Xa-induced signaling, migration, and invasion of breast cancer cells. Cancer Res. 2006, 66, 307–314.
21. Soucek L, Lawlor ER, Soto D, et al. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nature Medicine, vol. 13, no. 10, pp. 1211–1218, 2007.
*Correspondence: • CIOLOFAN ALEXANDRU, MD, PhD student
”Victor Babes” University of Medicine and Pharmacy, Department of Surgery
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 004025620447
• CEAUSU AMALIA RALUCA*, MD, PhD, Lecturer
”Victor Babes” University of Medicine and Pharmacy, Department of Microscopic Morphology/ Histology, Angiogenesis Research Center, Timisoara
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 0040740872707
e-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it
• GAJE NELA PUSA, MD, PhD, Associate Professor
”Victor Babes” University of Medicine and Pharmacy, Department of Microscopic Morphology/ Histology, Angiogenesis Research Center Timisoara
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 0040256204476
• TUDOR ADELINA MARIA, student
”Victor Babes” University of Medicine and Pharmacy, Department of Microscopic Morphology/ Histology, Angiogenesis Research Center Timisoara
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 0040256204476
• CRETU OCTAVIAN, MD, PhD, Professor
”Victor Babes” University of Medicine and Pharmacy, Department of Surgery
Piata Eftimie Murgu no. 2, 300041, Timisoara, Timis, Romania, Phone: 0040256204476
• NICOLESCU AMALIA, MD, PhD, Teaching Assistant
„Vasile Goldis” Western University of Arad, Romania, Department of Intensive Care
No.86 Liviu Rebreanu Street, 310045, Arad, Romania, Phone: +40-257-212204