Overexpression of Vascular Endothelial Growth Factor A in Invasive Micropapillary Colorectal Carcinoma

Rosa, Marilin; Abdelbaqi, Maisoun; Bui, Katherine; Nasir, Aejaz; Shibata, David; Coppola, Domenico

doi:10.1177/107327481502200212

Cited by 8 publications

(4 citation statements)

References 20 publications

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“…VEGF-C and VEGF-D are important in the process of lymphangiogenesis, while VEGF-A, VEGF-B and placental growth factor are important in neovascularization[163-166]. The most potent pro-angiogenic growth factor, VEGF-A binds to its receptors VEGFR-1 and VEGFR-2 and thereby increases endothelial cell survival, proliferation, migration and differentiation[167,168].…”

Section: Pathophysiology Of Colorectal Pcmentioning

confidence: 99%

Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

Lemoine¹,

Sugarbaker²,

Speeten³

2016

WJG

120

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Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Besides the lymphatic and haematogenous routes of dissemination, CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity, which ultimately leads to peritoneal carcinomatosis (PC). PC is associated with a poor prognosis and bad quality of life for these patients in their terminal stages of disease. A loco-regional treatment modality for PC combining cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy has resulted in promising clinical results. However, this novel approach is associated with significant morbidity and mortality. A comprehensive understanding of the molecular events involved in peritoneal disease spread is paramount in avoiding unnecessary toxicity. The emergence of PC is the result of a molecular crosstalk between cancer cells and host elements, involving several well-defined steps, together known as the peritoneal metastatic cascade. Individual or clumps of tumor cells detach from the primary tumor, gain access to the peritoneal cavity and become susceptible to the regular peritoneal transport. They attach to the distant peritoneum, subsequently invade the subperitoneal space, where angiogenesis sustains proliferation and enables further metastatic growth. These molecular events are not isolated events but rather a continuous and interdependent process. In this manuscript, we review current data regarding the molecular mechanisms underlying the development of colorectal PC, with a special focus on the peritoneum and the role of the surgeon in peritoneal disease spread.

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Section: Pathophysiology Of Colorectal Pcmentioning

confidence: 99%

Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

Lemoine¹,

Sugarbaker²,

Speeten³

2016

WJG

120

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“…Angiogenesis is central to the growth and metastasis of cancers; and VEGF is the key driver of tumor neovascularization, progression, and malignant phenotype [ 29 , 45 ]. Additionally, cluster of differentiation 31 (CD31) also plays a complex role in tumor angiogenesis [ 46 ]. These observations provide a strong reason for the importance of VEGF and CD31 as a potential targets in modern cancer therapy by developing strategies that can inhibit VEGF and/or to disrupt its signaling pathway [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, cluster of differentiation 31 (CD31) also plays a complex role in tumor angiogenesis [ 46 ]. These observations provide a strong reason for the importance of VEGF and CD31 as a potential targets in modern cancer therapy by developing strategies that can inhibit VEGF and/or to disrupt its signaling pathway [ 45 , 46 ]. Herein, our findings were in harmony and elucidated that Ad-ΔB/TRAIL and Ad-ΔB/IL-12 combination treatment was associated with a clear reduction in the intratumor expression of VEGF, CD31-positive cells, and in the microvessel density than the effects mediated by Ad-ΔB alone; suggesting a co-operative interaction between the administered OAds and their delivered TRAIL and IL-12 genes in halting tumor-driven angiogenesis and neovascularization.…”

Section: Discussionmentioning

confidence: 99%

Combined therapy with oncolytic adenoviruses encoding TRAIL and IL-12 genes markedly suppressed human hepatocellular carcinoma both in vitro and in an orthotopic transplanted mouse model

El-Shemi

Ashshi

et al. 2016

J Exp Clin Cancer Res

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BackgroundGene-based virotherapy mediated by oncolytic viruses is currently experiencing a renaissance in cancer therapy. However, relatively little attention has been given to the potentiality of dual gene virotherapy strategy as a novel therapeutic approach to mediate triplex anticancer combination effects, particularly if the two suitable genes are well chosen. Both tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interleukin-12 (IL-12) have been emerged as promising pharmacological candidates in cancer therapy; however, the combined efficacy of TRAIL and IL-12 genes for treatment of human hepatocellular carcinoma (HCC) remains to be determined.MethodsHerein, we investigated the therapeutic efficacy of concurrent therapy with two armed oncolytic adenoviruses encoding human TRAIL gene (Ad-ΔB/TRAIL) and IL-12 gene (Ad-ΔB/IL-12), respectively, on preclinical models of human HCC, and also elucidated the possible underlying mechanisms. The effects of Ad-ΔB/TRAIL+Ad-ΔB/IL-12 combination therapy were assessed both in vitro on Hep3B and HuH7 human HCC cell lines and in vivo on HCC-orthotopic model established in the livers of athymic nude mice by intrahepatic implantation of human Hep3B cells.ResultsCompared to therapy with non-armed control Ad-ΔB, combined therapy with Ad-ΔB/TRAIL+Ad-ΔB/IL-12 elicited profound anti-HCC killing effects on Hep3B and HuH7 cells and on the transplanted Hep3B-orthotopic model. Efficient viral replication and TRAIL and IL-12 expression were also confirmed in HCC cells and the harvested tumor tissues treated with this combination therapy. Mechanistically, co-therapy with Ad-ΔB/TRAIL+Ad-ΔB/IL-12 exhibited an enhanced effect on apoptosis promotion, activation of caspase-3 and-8, generation of anti-tumor immune response evidenced by upregulation of interferon gamma (IFN-γ) production and infiltration of natural killer-and antigen presenting cells, and remarkable repression of intratumor vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) expression and tumor microvessel density.ConclusionsOverall, our data showed a favorable therapeutic effect of Ad-ΔB/TRAIL+Ad-ΔB/IL-12 combination therapy against human HCC, and may therefore constitute a promising and effective therapeutic strategy for treating human HCC. However, further studies are warranted for its reliable clinical translation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0353-8) contains supplementary material, which is available to authorized users.

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“…3). It was previously reported that VEGF-A was overexpressed in invasive micropapillary colorectal carcinoma [16]. This might contribute to a response to bevacizumab, which is a monoclonal antibody against VEGA-A.…”

Section: Discussionmentioning

confidence: 99%

Whole Genome Sequencing Analysis of a Stage IV Colon Cancer Patient with a 10-Year Disease-Free Survival following Systemic Chemotherapy/Bevacizumab

Yeatman¹,

Yang²,

Coppola

2018

Case Rep Gastroenterol

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It is rare that stage IV colon cancer is cured with chemotherapy. Here we report the long-term survival of a patient who presented with highly advanced disease characterized by a papillary architecture as well as porta hepatis lymph nodes but responded extremely well to FOLFIRI/bevacizumab. His original tumor underwent comprehensive genomic testing that included whole genome DNA sequencing, targeted sequencing, and RNA sequencing. These genetic results suggest the patient’s tumor harbored mutations in APC, KRAS, and TP53 as well as in PIK3CB. Moreover, the RNA-seq data suggested that the tumor belonged to the consensus molecular subtype 4, the “inflamed, immune phenotype,” with increased angiogenesis. Deep sequencing of highly responsive cancers may yield molecular insights into mechanisms underpinning a remarkable response.

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Overexpression of Vascular Endothelial Growth Factor A in Invasive Micropapillary Colorectal Carcinoma

Abstract: The strong coexpression of VEGF-A and CD31 suggests a prominent role of neoangiogenesis in these tumors.

Cited by 8 publications

References 20 publications

Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

Combined therapy with oncolytic adenoviruses encoding TRAIL and IL-12 genes markedly suppressed human hepatocellular carcinoma both in vitro and in an orthotopic transplanted mouse model

Whole Genome Sequencing Analysis of a Stage IV Colon Cancer Patient with a 10-Year Disease-Free Survival following Systemic Chemotherapy/Bevacizumab

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