Vascular Endothelial Factor ( Vegf )

We studied the correlation between the micro-vascular density and pathological tumor staging that revealed high positive correlation between MVD and tumor stage was observed (r = 0.606, p = 0.001). From the ROC curve, by applying the cut off value =37.63 MVD, the higher MVD above the cut off

Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).

Background: cancer has developed mechanisms to survive and resist drugs including methotrexate, a DHFR inhibitor

Therefore, the most notable P53-induced mechanisms in mediating this response are cell cycle arrest and apoptosis [18], which activation depends on the cellular context and the extent of damage [20].

Besides inducing apoptosis and controlling the cell cycle, p53 has been demonstrated to be a central component and key regulator of the metabolic stress machinery. The metabolic balance between glycolysis and oxidative phosphorylation is heavily coordinated by p53 activity, which is activated by

Angiogenesis must be present for this occur, allowing cancer to spread to the blood, "thus the higher the density of new blood vessels within some tumors, the higher is the risk of metastasis of that tumor" (Mandal, 2014). Tumors have been documented to grow and spread without a direct blood supply and due to this physicians' are trying to discover ways to block tumor angiogenesis by investigating natural and synthetic inhibitors called "antiangiogenic agents" (National Cancer Institute, 2011). The goal is to slow the growth of cancer or prevent the disease entirely. According to the National Cancer Institute, "when vascular endothelial growth factor (VEGF) and other endothelial growth factors bind to their receptors on endothelial cells, signals within these cells are initiated that promote the growth and survival of new blood vessels" (2011, p. 1).

SMAD4: this gene is responsible for transmitting of chemical signals from the cell surface of TGFb pathway. TGFB attaches to the cell surface sends signals to turn on the SMAD4 gene which complex with other proteins and sends signals into the nucleus to regulate the growth and proliferation of specific areas in

Angiogenesis—a fundamental physiological process entailing the creation of new blood vessels—is implicated in diseases such as cancer, retinopathy, and macular degeneration. Vascular endothelial growth factor receptor 2 (VEGFR2) plays an important role in angiogenesis as it implements microvascular permeability and neovascularization in response to vascular endothelial growth factor (VEGF) binding to it. Inactivation of the receptor serves as a viable treatment for angiogenesis-related illnesses. Current treatment plans include VEGF antibodies and/or VEGFR2

Receptors expressed by endothelial cells, bone marrow progenitors and various neural cell types. VEGFR1 is more abundant in glial cells and VEGFR2 in neurons

Through this experiment we have successfully cloned and expressed Crassostrea virginica homolog of hypoxia inducible factor-1. This transcription factor, Hif-1, has many unknown possible cellular signaling pathways. One possible pathway interaction is between Hif-1 and its role in apoptosis and cell cycle control, since one of the effect of hypoxia is cell death. In the apoptosis pathway, the tumor suppressor protein, p53, is inhibited via Mdm2. This pathway has not been fully determined yet in the eastern oyster, thus it is speculated that Hif-1α and p53 could interact directly or indirectly via Mdm2 (Schmid, 2004). Hif-1 and its control of cell cycle arrest can be evaluated using protein-protein interactions. In order to determine the actual pathway, the possible interaction of Hif-1 and Mdm2 can be tested for this indirect control of apoptosis.

This ability of malign cancer to make their way across basement membrane and into blood vessels is what makes cancer so fatal and impossible to be cure by surgery alone. The result of metastasis and invasion in normal tissue by cancer cells are often seen as one of the distinctive features of malignancy (Ruoslahti 1996). Even though the ability of invasion and metastasis are one of the hallmarks for cancer, these abilities are not unique to cancer cells as it can also occur during the early development stage of the embryo, in healthy organisms and in many noncancerous diseases (Mareel & Leroy 2003). It does not matter whenever the organism has developed benign or malign cancer, all cancer cells have the ability to disturb the normal cell cycle and threaten the survival of the organism.

Through the successes of molecular biology in the last 30 more years, we now understand that oncogenes and tumor suppressor genes encode many cellular signal pathways that not only sustain cancer proliferation but also reprogram cancer energy metabolism to meet the biosynthetic challenge associated with the cancer cells growth and proliferation (Hanahan and Weinberg, 2011; Vander Heiden et al., 2009; Ward and Thompson, 2012a). Many signaling pathways including PI3K/Akt/mTORC1 and HIF are involved in cancer metabolic reprograming for cellular biosynthesis (Jones and Thompson, 2009; Ward and Thompson, 2012a, b). Furthermore, oncogenes and tumor suppressors have been found to be critical components of these metabolic

In about a third of primary ovarian tumour, EEF1A2 is raised in copy number, and whilst EEF1A2 mRNA is not measurable in normal ovarian epithelium, the rate of EEF1A2 mRNA is increased in a third of ovarian tumours. It appears here that EEF1A2 is an important ovarian cancer oncogene (Lee, 2003). Moreover, when the eEF1A2 expression is induced in human ovarian cell line, the eEF1A2 expressing cell line is more tumorigenic; this proves that eEF1A2 promotes malignancy in ovarian cells (Anand et al., 2002). EEF1A2 is also an oncogene in lung adenocarcinoma (Li et al., 2006). And in a high proportion of pancreatic carcinoma, eEF1A2 is up-regulated while it is just a little bit expressed in normal pancreas (Cao et al., 2009). EEF1A2 over-expression seems to enhance cell growth, proliferation, motility, survival and invasion of pancreatic cancer cells (Cao et al., 2009). In two third of breast cancer, EEF1A2 is over-expressed, which indicates that eEF1A2 might be an oncoprotein (Tomlinson et al., 2005). But interestingly, it has been shown that eEF1A2 also augurs

Hypoxia is a characteristic feature of most solid tumors. Hypoxia induces tumor chemoresistance in proportion to distance from the vasculature. Hypoxic cells are exposed to less chemo

For metastatic outgrowth extravasation of tumor cells and secondary seeding are important. In secondary organs fibronectin expression is upregulated by primary tumors via resident fibroblasts, which serves as a docking site for VEGFR1+ hematopoietic progenitor cell (HPC) clusters and secondary seeding. During metastasis of breast cancer to lung, interaction of VCAM-1+ cancer cells with VLA-4-expressing macrophages, activates PI3K/Akt signaling in tumor cells, protecting them from caspase-induced apoptosis. Bone metastasis is also facilitated by interaction of VCAM1 with different integrin partner, α4β1, in osteoclasts. Thus, we can conclude that disruption of adhesion signaling between stromal cells and tumor cells can