Cancer Research and Treatment

Original Articles

Breast cancer

Clinical Significance of Major Angiogenesis-Related Effectors in Patients with Metastatic Breast Cancer Treated with Trastuzumab-Based Regimens: Helen P. Kourea, Foteinos-Ioannis Dimitrakopoulos, Georgia-Angeliki Koliou, Anna Batistatou, Kyriaki Papadopoulou, Mattheos Bobos, Anthoula Asimaki-Vlachopoulou, Sofia Chrisafi, Kitty Pavlakis, Kyriakos Chatzopoulos, Eleni Galani, George Pentheroudakis, Dimitrios Pectasides, Dimitrios Bafaloukos, Eleni Res, Pavlos Papakostas, Angelos Koutras, Vassiliki Kotoula, George Fountzilas; Cancer Res Treat. 2022;54(4):1053-1064. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.748

Abstract PDF Supplementary Material PubReader ePub

Purpose
Angiogenesis is a crucial phenomenon in the development and progression of breast cancer (BC), but the clinical significance of angiogenesis-related proteins in metastatic BC remains unknown. This study investigates the prognostic value of vascular endothelial growth factor receptors 1, 2, 3 (VEGFR1, VEGFR2, VEGFR3) as well as vascular endothelial growth factors A and C (VEGFA and VEGFC) in metastatic BC patients treated with trastuzumab-based regimens.
Materials and Methods
Two hundred female patients were included. Protein and mRNA expression of the studied angiogenesis-related factors were evaluated by immunohistochemistry and quantitative polymerase chain reaction, respectively.
Results
High expression of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in the tumor cells was observed in 43.5%, 24.2%, 36%, 29.5%, and 43%, respectively. Stromal elements expressed high levels of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in 78.9%, 93.3%, 90.7%, 90.2%, and 74.8% of tumors with available data. High tumor cell expression of VEGFR1 was a favorable prognosticator for survival among patients with human epidermal growth factor receptor 2 (HER2)–positive tumors (hazard ratio [HR], 0.55; p=0.013). A trend towards longer progression-free survival was detected univariately for patients with HER2-negative tumors and high expression of VEGFR2 (HR, 0.60; p=0.059).
Conclusion
VEGFR1 and VEGFR2 seem to have significant prognostic value in BC patients with metastatic disease treated with trastuzumab-based regimens.

Citations

Citations to this article as recorded by

Apatinib beyond first progression is associated with prolonged overall survival in patients with advanced breast cancer: Results from an observational study
Jing Wang, Jinghao Jia, Jingjing Liu, Xuemin Yao, Zhiyong Yuan
Experimental and Therapeutic Medicine.2024;[Epub] CrossRef

5,566 View
110 Download
2 Web of Science
1 Crossref

No Association of Vascular Endothelial Growth Factor-A (VEGF-A) and VEGF-C Expression with Survival in Patients with Gastric Cancer: Soo Jung Lee, Jong Gwang Kim, Sang Kyun Sohn, Yee Soo Chae, Joon Ho Moon, Shi Nae Kim, Han-Ik Bae, Ho Young Chung, Wansik Yu; Cancer Res Treat. 2009;41(4):218-223. Published online December 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.4.218

Abstract PDF PubReader ePub

Purpose

Although the vascular endothelial growth factor (VEGF) superfamily has been identified to critically influence tumor-related angiogenesis, the prognostic significance of a VEGF expression in gastric cancer is still controversial. Accordingly, the present study analyzed the VEGF-A and VEGF-C expressions and their impact on the prognosis of patients with gastric cancer.

Materials and Methods

Three hundred seventy-five consecutive patients who underwent surgical resection for gastric adenocarcinoma with a curative intent were enrolled in the present study. Immunohistochemical staining for VEGF-A and VEGF-C was performed using the formalin fixed, paraffin embedded tumor tissues.

Results

Positive VEGF-A and VEGF-C expressions were observed in 337 (90.1%) and 278 (74.9%) cases, respectively. The survival analysis showed that the expression of VEGF-A and VEGF-C had no effect on the OS and DFS. On the multivariate analysis that included age, gender and the TNM stage, no significant association between the grade of the VEGF-A or VEGF-C expression and survival was observed.

Conclusion

The current study suggests that the tissue expression of VEGF-A or VEGF-C alone is not an independent prognostic marker for patients with surgically resected gastric adenocarcinoma.

Citations

Citations to this article as recorded by

Proposed Molecular and miRNA Classification of Gastric Cancer
Lara Alessandrini, Melissa Manchi, Valli De Re, Riccardo Dolcetti, Vincenzo Canzonieri
International Journal of Molecular Sciences.2018; 19(6): 1683. CrossRef
Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab
Charles S Fuchs, Josep Tabernero, Jiří Tomášek, Ian Chau, Bohuslav Melichar, Howard Safran, Mustapha A Tehfe, Dumitru Filip, Eldar Topuzov, Luis Schlittler, Anghel Adrian Udrea, William Campbell, Stephen Brincat, Michael Emig, Symantha A Melemed, Rebecca
British Journal of Cancer.2016; 115(8): 974. CrossRef
Fentanyl inhibits the progression of human gastric carcinoma MGC-803 cells by modulating NF-κB-dependent gene expression in vivo
GUODONG HE, LI LI, ENJIAN GUAN, JING CHEN, YI QIN, YUBO XIE
Oncology Letters.2016; 12(1): 563. CrossRef
Disrupted Balance of MMPs/TIMPs in Gastric Carcinogenesis–Paradoxical Low MMP-2 Expression in Tumor and Stromal Compartments as a Potential Marker of Unfavorable Outcome
Piotr Donizy, Julia Rudno-Rudzinska, Maciej Kaczorowski, Jedrzej Kabarowski, Ewelina Frejlich, Wojciech Kielan, Rafal Matkowski, Agnieszka Halon
Cancer Investigation.2015; 33(7): 286. CrossRef
The different role of intratumoral and peritumoral lymphangiogenesis in gastric cancer progression and prognosis
Kyung Ho Pak, Ara Jo, Hye Ji Choi, Younghee Choi, Hyunki Kim, Jae-Ho Cheong
BMC Cancer.2015;[Epub] CrossRef
Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy
Ismael Riquelme, Kathleen Saavedra, Jaime A. Espinoza, Helga Weber, Patricia García, Bruno Nervi, Marcelo Garrido, Alejandro H. Corvalán, Juan Carlos Roa, Carolina Bizama
Oncotarget.2015; 6(28): 24750. CrossRef
VEGF-C expression is associated with the poor survival in gastric cancer tissue
Weiguo Cao, Rong Fan, Weiping Yang, Yunlin Wu
Tumor Biology.2014; 35(4): 3377. CrossRef
VEGF-A clinical significance in gastric cancers: Immunohistochemical analysis of a wide Italian cohort
E. Lastraioli, L. Boni, M.R. Romoli, S. Crescioli, A. Taddei, S. Beghelli, A. Tomezzoli, C. Vindigni, L. Saragoni, L. Messerini, M. Bernini, L. Bencini, E. Giommoni, G. Freschi, F. Di Costanzo, A. Scarpa, P. Morgagni, M. Farsi, F. Roviello, G. De Manzoni,
European Journal of Surgical Oncology (EJSO).2014; 40(10): 1291. CrossRef
Prognostic value of vascular endothelial growth factor A expression in gastric cancer: a meta-analysis
Ya-nan Ji, Qin Wang, Yang Li, Zhi Wang
Tumor Biology.2014; 35(3): 2787. CrossRef
Clinicopathologic Significance of Nuclear Factor-κB and Vascular Endothelial Growth Factor Expression in Advanced Gastric Cancer Patients
Keon Woo Park, Su-Jin Kim, Sung Yong Oh
Oncology Research and Treatment.2014; 37(4): 183. CrossRef
Prognostic Value of Vascular Endothelial Growth Factor Expression in Resected Gastric Cancer
Lei Liu, Xue-Lei Ma, Zhi-Lan Xiao, Mei Li, Si-Hang Cheng, Yu-Quan Wei
Asian Pacific Journal of Cancer Prevention.2012; 13(7): 3089. CrossRef
Potential prognostic and therapeutic role for angiogenesis markers in laryngeal carcinoma
Marco Lionello, Alberto Staffieri, Gino Marioni
Acta Oto-Laryngologica.2012; 132(6): 574. CrossRef
Prognostic significance of vascular endothelial growth factor immunohistochemical expression in gastric cancer: a meta-analysis
Ling Peng, Ping Zhan, Yun Zhou, Weijia Fang, Peng Zhao, Yulong Zheng, Nong Xu
Molecular Biology Reports.2012; 39(10): 9473. CrossRef
Protein Kinase B Phosphorylation Correlates with Vascular Endothelial Growth Factor A and Microvessel Density in Gastric Adenocarcinoma
Xd Zhou, Hx Chen, Rn Guan, Yp Lei, X Shu, Y Zhu, Nh Lv
Journal of International Medical Research.2012; 40(6): 2124. CrossRef
Prognostic significance of vascular endothelial growth factor expression in gastric carcinoma: a meta-analysis
Jing Chen, Tao Li, Yuanyuan Wu, Lijun He, Li Zhang, Tieliu Shi, Zhengfang Yi, Mingyao Liu, Xiufeng Pang
Journal of Cancer Research and Clinical Oncology.2011; 137(12): 1799. CrossRef
Vascularization of testicular germ cell tumours: evidence from experimental teratocarcinomas
U. Silván, A. Díez‐Torre, L. Jiménez‐Rojo, J. Aréchaga
International Journal of Andrology.2010; 33(6): 765. CrossRef
Cancer-associated fibroblasts are positively correlated with metastatic potential of human gastric cancers
Kangkang Zhi, Xiaojun Shen, Hao Zhang, Jianwei Bi
Journal of Experimental & Clinical Cancer Research.2010;[Epub] CrossRef

10,760 View
66 Download
17 Crossref

Review Article

Improving Conventional or Low Dose Metronomic Chemotherapy with Targeted Antiangiogenic Drugs: Robert S. Kerbel; Cancer Res Treat. 2007;39(4):150-159. Published online December 31, 2007; DOI: https://doi.org/10.4143/crt.2007.39.4.150

Abstract PDF PubReader ePub

One of the most significant developments in medical oncology practice has been the approval of various antiangiogenic drugs for the treatment of a number of different malignancies. These drugs include bevacizumab (Avastin®), the anti-VEGF monoclonal antibody. Thus far, bevacizumab appears to induce clinical benefit in patients who have advanced metastatic disease only or primarily when it is combined with conventional chemotherapy. The reasons for the chemo-enhancing effects of bevacizumab are unknown, and this is a subject that we have been actively studying along with additional ways that antiangiogenic drugs may be combined with chemotherapy. In this respect, we have focused much of our effort on metronomic low dose chemotherapy. We have been studying the hypothesis that some chemotherapy drugs at maximum tolerated doses or other cytotoxic- like drugs such as acute "vascular disrupting agents" (VDAs) can cause an acute mobilization of proangiogenic cells from the bone marrow which home to and colonize the treated tumors, thus accelerating their recovery. These cells include endothelial progenitor cells. This systemic process can be largely blocked by a targeted antiangiogenic drug, e.g. anti-VEGFR-2 antibodies. In addition, metronomic chemotherapy, i.e., close regular administration of chemotherapy drugs at low non-toxic doses with no breaks, over prolonged periods of time not only prevents the acute CEP bone marrow response, but can even target the cells. This potential antiangiogenic effect of metronomic chemotherapy can also be boosted by combination with a targeted antiangiogenic agent. Treatment combinations of metronomic chemotherapy and an antiangiogenic drug have moved into phase II clinical trial testing with particularly encouraging results thus far reported in metastatic breast and recurrent ovarian cancer. Oral chemotherapy drugs such as cyclophosphamide (CTX), methotrexate are the main chemotherapeutics used for such trials. Oral 5-FU prodrugs such as UFT would also appear to be highly suitable based on long term adjuvant therapy studies in patients. Recent preclinical results using metronomic cyclophosphamide and metronomic UFT in models of advanced metastatic breast cancer suggest that this type of combination might be particularly promising for metronomic chemotherapy in this indication, particularly when combined with a targeted antiangiogenic drug.

Citations

Citations to this article as recorded by

Metronomic Chemotherapy Based on Topotecan or Topotecan and Cyclophosphamide Combination (CyTo) in Advanced, Pretreated Ovarian Cancer
Piotr J. Wysocki, Mateusz Łobacz, Paweł Potocki, Łukasz Kwinta, Anna Michałowska-Kaczmarczyk, Agnieszka Słowik, Kamil Konopka, Anna Buda-Nowak
Cancers.2023; 15(4): 1067. CrossRef
Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature
Benjamin Carcamo, Giulio Francia
Journal of Clinical Medicine.2022; 11(10): 2849. CrossRef
Muscarinic Receptors Associated with Cancer
Gloria M. Calaf, Leodan A. Crispin, Juan P. Muñoz, Francisco Aguayo, Tammy C. Bleak
Cancers.2022; 14(9): 2322. CrossRef
De-escalating cancer treatments during COVID 19 pandemic: Is metronomic chemotherapy a reasonable option?
Palma Fedele, Valeria Sanna, Alessandro Fancellu, Antonella Marino, Nicola Calvani, Saverio Cinieri
Critical Reviews in Oncology/Hematology.2021; 157: 103148. CrossRef
Metronomics in Pediatric Oncology: Lessons Learned and the Way Forward
Raja Pramanik, Sameer Bakhshi
Indian Journal of Medical and Paediatric Oncology.2020; 41(03): 317. CrossRef
Optimal Impulsive Control With Application to Antiangiogenic Tumor Therapy
Filippo Cacace, Valerio Cusimano, Pasquale Palumbo
IEEE Transactions on Control Systems Technology.2020; 28(1): 106. CrossRef
Adeno-associated virus 2 mediated gene transfer of vascular endothelial growth factor Trap: a new treatment option for glioma
Shengnan Zhao, Yakun Zhang, Lei Wang, Li Yang, Liqun Zou, Fabao Gao
Cancer Biology & Therapy.2019; 20(1): 65. CrossRef
Tumor endothelial cells as a potential target of metronomic chemotherapy
Ji Yoon Kim, Young-Myeong Kim
Archives of Pharmacal Research.2019; 42(1): 1. CrossRef
Analyses of the Temperature Field of a Piezoelectric Micro Actuator in the Endoscopic Biopsy Channel
Pancheng Zhu, Hanmin Peng, Jianzhi Yang
Applied Sciences.2019; 9(21): 4499. CrossRef
The use of low‐dose metronomic chemotherapy in dogs—insight into a modern cancer field
T. B. Gaspar, J. Henriques, L. Marconato, F. L. Queiroga
Veterinary and Comparative Oncology.2018; 16(1): 2. CrossRef
Dental pulp stem cells used to deliver the anticancer drug paclitaxel
Hamideh Salehi, Siham Al-Arag, Elodie Middendorp, Csilla Gergely, Frederic Cuisinier, Valerie Orti
Stem Cell Research & Therapy.2018;[Epub] CrossRef
Low-Dose Continuous 5-Fluorouracil Combined with Leucovorin, nab-Paclitaxel, Oxaliplatin, and Bevacizumab for Patients with Advanced Pancreatic Cancer: A Retrospective Analysis
William H. Isacoff, Howard A. Reber, Rudolph Bedford, William Hoos, Lola Rahib, Alexander Upfill-Brown, Timothy Donahue, O. Joe Hines
Targeted Oncology.2018; 13(4): 461. CrossRef
Phase II study of pazopanib in combination with paclitaxel in patients with metastatic melanoma
John P. Fruehauf, Monica El-Masry, Katherine Osann, Basmina Parmakhtiar, Maki Yamamoto, James G. Jakowatz
Cancer Chemotherapy and Pharmacology.2018; 82(2): 353. CrossRef
Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer
Koji Harada, Tarannum Ferdous, Yoshiya Ueyama
Japanese Dental Science Review.2017; 53(3): 61. CrossRef
Optimal discrete time control of antiangiogenic tumor therapy
Dániel András Drexler, Johanna Sápi, Levente Kovács
IFAC-PapersOnLine.2017; 50(1): 13504. CrossRef
Nanometronomic treatment of 4T1 breast cancer with nanocaged doxorubicin prevents drug resistance and circumvents cardiotoxicity
Serena Mazzucchelli, Michela Bellini, Luisa Fiandra, Marta Truffi, Maria A. Rizzuto, Luca Sorrentino, Erika Longhi, Manuela Nebuloni, Davide Prosperi, Fabio Corsi
Oncotarget.2017; 8(5): 8383. CrossRef
Penetration and Silencing Activity of VEGF Dicer Substrate siRNA Vectorized by Chitosan Nanoparticles in Monolayer Culture and a Solid Tumor ModelIn Vitrofor Potential Application in Tumor Therapy
Maria Abdul Ghafoor Raja, Haliza Katas, Zariyantey Abd Hamid
Journal of Nanomaterials.2016; 2016: 1. CrossRef
Maintenance Treatment with Oral Cyclophosphamide and Bevacizumab in Patients with Recurrent Epithelial Ovarian Cancer
Roberto Petrioli, Giandomenico Roviello, Anna Ida Fiaschi, Letizia Laera, Salvatora Tindara Miano, Daniele Marrelli, Franco Roviello, Vincenzo Bianco, Edoardo Francini
Future Oncology.2015; 11(18): 2563. CrossRef
Potent efficacy of metronomic topotecan and pazopanib combination therapy in preclinical models of primary or late stage metastatic triple-negative breast cancer
Teresa Di Desidero, Ping Xu, Shan Man, Guido Bocci, Robert S. Kerbel
Oncotarget.2015; 6(40): 42396. CrossRef
Metronomic oral paclitaxel shows anti-tumor effects in an orthotopic mouse model of ovarian cancer
Ho-Suap Hahn, Ki-Heon Lee, In-Ho Lee, Jae-Ho Lee, Chang-Sung Whang, Yeong-Woo Jo, Tae-Jin Kim
Journal of Gynecologic Oncology.2014; 25(2): 130. CrossRef
Metronomic oral cyclophosphamide (MOC) in the salvage therapy of heavily treated recurrent ovarian cancer patients: a retrospective, multicenter study
Gabriella Ferrandina, Giacomo Corrado, Floriana Mascilini, Paola Malaguti, Riccardo Samaritani, Mariagrazia Distefano, Valeria Masciullo, Alessia Di Legge, Antonella Savarese, Giovanni Scambia
BMC Cancer.2014;[Epub] CrossRef
Weekly Administration of Bevacizumab, Gemcitabine, and Oxaliplatin in Patients With Recurrent and Refractory Ovarian Cancer
Yuji Ikeda, Masashi Takano, Katsutoshi Oda, Hiroko Kouta, Tomoko Goto, Kazuya Kudoh, Naoki Sasaki, Tsunekazu Kita, Yoshihiro Kikuchi
International Journal of Gynecological Cancer.2013; 23(2): 355. CrossRef
Efficacy of schedule-dependent metronomic S-1 chemotherapy in human oral squamous cell carcinoma cells
TARANNUM FERDOUS, KOJI HARADA, TAKANORI KIN, TOYOKO HARADA, YOSHIYA UEYAMA
International Journal of Oncology.2013; 43(1): 271. CrossRef
Eradication of breast cancer cells in patients with distant metastasis: the finishing touches?
Yoshinori Ito, Takuji Iwase, Kiyohiko Hatake
Breast Cancer.2012; 19(3): 206. CrossRef
First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study
Veronica Marchetti, Mario Giorgi, Anna Fioravanti, Riccardo Finotello, Simonetta Citi, Bastianina Canu, Paola Orlandi, Teresa Di Desidero, Romano Danesi, Guido Bocci
Investigational New Drugs.2012; 30(4): 1725. CrossRef
Exploratory predictive and prognostic factors in advanced breast cancer treated with metronomic chemotherapy
Manuela Miscoria, Fabrizio Tonetto, Laura Deroma, Piernicola Machin, Carla Di Loreto, Pamela Driol, Alessandro Marco Minisini, Stefania Russo, Claudia Andreetta, Mauro Mansutti, Giuseppe Damante, Gianpiero Fasola, Fabio Puglisi
Anti-Cancer Drugs.2012; 23(3): 326. CrossRef
Are there opportunities for chemotherapy in the treatment of hepatocellular cancer?
Uzma Asghar, Tim Meyer
Journal of Hepatology.2012; 56(3): 686. CrossRef
Metronomic therapy for gynecologic cancers
Wen-Hsiang Su, Tien-Yu Ho, Yiu-Tai Li, Chien-Hsing Lu, Wen-Ling Lee, Peng-Hui Wang
Taiwanese Journal of Obstetrics and Gynecology.2012; 51(2): 167. CrossRef
Controlling escape from angiogenesis inhibitors
Barbara Sennino, Donald M. McDonald
Nature Reviews Cancer.2012; 12(10): 699. CrossRef
Sequential bevacizumab and oral cyclophosphamide for recurrent ovarian cancer
Ursula A. Matulonis, Lauren Pereira, Joyce Liu, Hang Lee, Julie Lee, Christin Whalen, Susana Campos, Tina Atkinson, Margaret Hill, Suzanne Berlin
Gynecologic Oncology.2012; 126(1): 41. CrossRef
Tumor angiogenesis: molecular pathways and therapeutic targets
Sara M Weis, David A Cheresh
Nature Medicine.2011; 17(11): 1359. CrossRef
Suppression of hepatic tumor growth and metastasis by metronomic therapy in a rat model of hepatocellular carcinoma
Jeong Won Jang, Seong Tae Park, Jung Hyun Kwon, Chan Ran You, Jong Young Choi, Chan-Kwon Jung, Si Hyun Bae, Seung Kew Yoon
Experimental and Molecular Medicine.2011; 43(5): 305. CrossRef
Off-tumor target—beneficial site for antiangiogenic cancer therapy?
Yihai Cao
Nature Reviews Clinical Oncology.2010; 7(10): 604. CrossRef
Optimizing the Delivery of Cancer Drugs That Block Angiogenesis
Yihai Cao, Robert Langer
Science Translational Medicine.2010;[Epub] CrossRef
New anti-angiogenic strategies in pediatric solid malignancies: agents and biomarkers of a near future
Melissa Taylor, Jochen Rössler, Birgit Geoerger, Gilles Vassal, Françoise Farace
Expert Opinion on Investigational Drugs.2010; 19(7): 859. CrossRef
Metronomic Gemcitabine in Combination with Sunitinib Inhibits Multisite Metastasis and Increases Survival in an Orthotopic Model of Pancreatic Cancer
Hop S. Tran Cao, Michael Bouvet, Sharmeela Kaushal, Alex Keleman, Eric Romney, Ginna Kim, John Fruehauf, David K. Imagawa, Robert M. Hoffman, Matthew H.G. Katz
Molecular Cancer Therapeutics.2010; 9(7): 2068. CrossRef
Penetration and efficacy of VEGF siRNA using polyelectrolyte complex micelles in a human solid tumor model in-vitro
Ahmed M. Al-Abd, Soo Hyeon Lee, Sun Hwa Kim, Jung-Ho Cha, Tae Gwan Park, Seung Jin Lee, Hyo-Jeong Kuh
Journal of Controlled Release.2009; 137(2): 130. CrossRef

15,668 View
121 Download
37 Crossref

Original Articles

VEGF Expression and MVD in Ductal Carcinoma of Breast: Seong Jon Jeong, Sung Jun Park, Sung Jae Cha, Young Kum Park, Kyong Choun Chi, Hyun Mook Lim, Sung II Park, Tae Jin Lee, Un Sub Park; J Korean Cancer Assoc. 1999;31(6):1168-1178.

Abstract PDF: PURPOSE
This study was aimed to determine the role of the VEGF and MVD expression in infiltrating ductal carcinoma of breast and to observe the correlation between the expression of these VEGF/MVD, and other prognostic factors.
MATERIALS AND METHODS
Immunohistochemical staining of VEGF and MVD with monoclonal antibody in pathologic specimens of 35 patients of infiltrating ductal carcinoma of breast was carried out. Reiationship between the expression of the VEGF/MVD and prognostic factors were assessed.
RESULTS
The VEGF/MVD expression was closely related to tumor size, lymph node metastasis, and clinical stage, but not related to histologic grade, nuclear grade, estrogen receptor, and progestrone receptor. And the VEGF expression was closely related to MVD.
CONCLUSION
The VEGF expression and microvessel density in infiltrating ductal carcinoma of breast may play an important prognostic factors, closely related to the tumor size, lymph node metastasis, and stage.

2,552 View
18 Download

Prognostic Significance of VEGF in Human Stomach Cancer: Gue Sung Han, Sung Jae Cha, Young Kum Park, Kyong Choun Chi, Sung Jun Park, Hyun Mook Lim, Sung II Park, Un Sub Park; J Korean Cancer Assoc. 1999;31(6):1087-1093.

Abstract PDF: PURPOSE
Angiogenesis plays an important role in the growth, progression and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) was thought to be one such angiogenic factor and was also thought to be a selective mitogen for endothelial cells. The purpose of this retrospective study was to evaluate for prognostic significance of VEGF in stomach cancer.
MATERIALS AND METHODS
The sections of formalin-fixed, paraffin embedded from 55 stomach cancer were stained immunohistochemically for VEGF. The rate of VEGF expression and correlation between expression of VEGF and other prognostic factor of stomach cancer were studied.
RESULTS
There were 20 cases (36.4%) of VEGF-positive and 35 cases (63.6%) of VEGF- negative. There were no significant difference between VEGF expression and the histologic type, differentiation, depth of invasion of histologic stage, lymph node involvement. The frequency of hepatic recurrence was higher in patients with VEGF-positive tumor than that af patient with negative tumor (p=0.007). The prognosis of the patients with VEGF positive tumor was worse than that of patients with VEGF negative tumor (p=0.0214).
CONCLUSION
There was a closely significant between positive expression of VEGF and a high incidence of hepatic metastasis, low survival rate. The expression of VEGF could be considered to be one of useful prognostic factor in human gastric carcinoma

2,564 View
14 Download

Angiogenesis and Proliferating Cell Nuclear Antigen Index in Non-small Cell Lung Carcinomas: Chang Hoon Lee, Kang Suek Suh; J Korean Cancer Assoc. 1999;31(5):1054-1064.

Abstract PDF: PURPOSE
This study aimed to determine the relationship between angiogenesis and tumor cell proliferation evaluated by proliferating cell nuclear antigen (PCNA) in non-small cell lung carcinomas (NSCLCs) and to investigate the prognostic significance of the factors in them.
MATERIALS AND METHODS
Immunohistochemical staining for factor VIII related antigen, vascular endothelial growth factor (VEGF) and PCNA was performed using paraffin embedded blocks of 57 NSCLC cases. The results were correlated with some clinicopathologic parameters, including age, sex, TNM-T status, TNM-N status, stage, and histologic type.
RESULTS
Microvessel count (MC) was higher in squamous cell carcinoma group than in non-squamous cell carcinoma one (18.4+/-7.3 vs 14.6+/-9.9, p=0.043). PCNA index was higher in lymph node metastasis group than in non-metastasis one (42.1+/-8.9% vs 36.4+/- 14.6%, p=0.043). But the factors were not correlated with other clinicopathologic parameters. The relationship between VEGF expression and MC was significantly recognized (p=0.02), but that between VEGF expression and PCNA index was not. MC was positively correlated with PCNA index (r=0.547, p=0.005).
CONCLUSION
These findings suggest that both MC and PCNA index can be acted as useful indicators of prognosis in NSCLC, but tumor cell proliferation in NSCLC may be more concerned with any growth factor other than VEGF.

2,934 View
14 Download

Correlation between VEGF Expression and Prognostic Factors in Breast Cancer: Jung Eun Jang, Sang Yun Choi, Chan Hyung Park, Young Hyeh Ko, Ki Hyun Kim, Hyun Sik Jeong, Kwang Sung Ahn, Jung Hyun Yang, Seok Jin Nam, Sung Soo Yoon; J Korean Cancer Assoc. 1999;31(3):483-491.

Abstract PDF: PURPOSE
Archival tissues of breast cancer patients were examined for VEGF expression to evaluate the relationship with other clinicopathologic factors and prognostic significance of VEGF in breast cancer.
MATERIALS AND METHODS
Paraffin sections from 76 patients with invasive breast cancer who have been treated at Samsung Medical Center from December, 1994 to April, 1998 were examined for VEGF expression by immunohistochemical staining using anti-VEGF antibody. We analyzed relationships between VEGF expression and tumor size, tumor stage, metastasis, steroid honnone receptors, p53, disease recurrence and survival.
RESULTS
Immunostaining showed variable VEGF positivity in the malignant cells and VEGF was detected more frequently in tumors than in adjacent non-tumorous breast tissues. 74 out of 76 (97.4%) was positive for VEGF. We found that the expression of VEGF was strongly correlated with the stages of breast tumor (P=0.020), lymph node metastasis (P=0.043) and PR (P=0.016). However, we could not find statistically significant relationship between VEGF expression and tumor size, ER, p53 and distant metastasis.
CONCLUSION
VEGF may be a useful prognostic indicator in patients with breast cancer, especially correlated with tumor stage and lymph node metastasis. This result warrants further study to confirm our findings.

3,693 View
32 Download

Correlation between VEGF Expression and Angiogenesis in Advanced Gastric Carcinoma: Young Bae Kim, Jee Young Han, Sang Hyun Lee, Hae Seung Han, Tae Sook Kim, Young Chae Chu, Tae Sook Hwang; J Korean Cancer Assoc. 1998;30(6):1061-1068.

Abstract PDF: PURPOSE
VEGF is thought to be an important angiogenic factor playing significant a role in the aggressiveness of malignant tumor by stimulating neovascularization. We morphologically investicated the tumor angiogenesis in terms of the presence of VEGF expression in advanced gastric carcinoma.
MATERIALS AND METHODS
We performed immunohistochemical stains for VEGF, CD 34, and MIB-1 (Ki-67) on the 51 paraffin-embedded tissue sections. The degree of angiogenesis was determined by counting microvessel densities and their Ki-67 labelling indices of endothelial cells within the tumors. We evaluated the correlation between the expression of VEGF, angiogenesis and clinicopathologic factors such as histologic differentiation, depth of invasion, and lymph node metastasis.
RESULTS
Immunoreactivity for VEGF revealed positivity in 34 out of 51 cases (66.7%). Microvessel densities and Ki-67 labelling indices of endothelial cells reflecting angiogenesis were higher in VEGF-positive tumors than VEGF-negative tumors. There were no conelations between VEGF expression, histologic differentiation and the depth of invasion. We failed to evaluate the conelation of VEGF expression and lymph node metastasis.
CONCLUSION
This study suggests that VEGF expressian is closely related to tumor asso- ciated angiogenesis in advanced gastric carcinoma. Considering that tumor growth depends on angiogenesis, therapies reducing VEGF may be a means of inhibiting angiogenesis and tumor aggressiveness.

3,332 View
14 Download

Studies on the Mechanism of Hypoxic Increase of VEGF Expression in the Hep3B Human Hepatoma Cells: Yoo Wook Kwon, Soo Kyung Bae, Jung Ae Kim, Kyu Won Kim, Byung Chae Park; J Korean Cancer Assoc. 1997;29(2):220-226.

Abstract PDF: PURPOSE
Hepatocellular carcinoma (HCC), a typical hypervasculized tumor is very sensitive to hypoxia and vascular endothelial growth factor (VEGF) has previously been identified to be up-regulated in response to hypoxia in several cell types. However, the molecular mechanisms by which hypoxia is sensed by the cells remain enigmatic. To investigate whether calcium and AP-1 are involved in hypoxia-sensing mechanism, we performed following experiments.
MATERIALS AND METHODS
Hep3B cells were grown in hypoxic condition. To assess cell viability, MTT assay was performed. To investigate the effect of calcium and AP-1, northern blot analysis was performed after treatment with BAPTA/AM.
RESULTS
The expression of VEGF was significantly up-regulated by hypoxia in Hep3B, hepatocellular carcinoma cell line. The increased expression of VEGF induced by hypoxia was blocked by the addition of BAPTA/AM, a cytosolic calcium chelator to the media. In addition, we found that the expression of c-jun protooncogene was also up-regulated by hypoxia. Hypoxic increase of c-jun expression was also normalized by the treatment with BAPTA/AM.
CONCLUSION
These results suggest that the increased expression of VEGF by hypoxia is mediated through the calcium and c-jun signalling pathway in the Hep3B human hepatoma cell lines.

2,386 View
15 Download

First
Prev
Page of 1
Next
Last

Search