Angiogenesis in Malignancies - Essay Example

? "Angiogenesis in Malignancies" (Angiogenin) Credentials: Department: Contact information: Word Count: Key Words: Angiogenesis,Cancer Cells, Tumor Cells, Human Body, Angiogenic Phenotype, Proliferation, Lymphatic Vessels, Body Cavity, Blood Vessels, Capillaries, Neovascularization, Metastasis, Basal Cell Carcinoma Introduction Undeniably, angiogenesis undertakes an extremely indispensable role in growth and proliferation of varied human body cells as well as tissues. These include development of vascular tissues, restoration of wounds besides being responsible for placenta growth. However, angiogenesis in some circumstances due to varied abnormalities fail to operate within its mandated natural guidelines. Hence, result to lack of the appropriate production control evident when the process results to either too little or too much rate of angiogenesis. This is especially apparent among people experiencing abnormal development of tumors and other vascular related predicaments like cancer. Hence, act as the source of the current medical field’s worry though some scholars are currently advocating the predicament by advocating starving cells as an effective way of putting it at a bay (1). The intricacy of dealing with abnormalities caused by angiogenesis results from partial knowledge, which the medical field currently has especially in the way the process usually takes place in humans. Hence, becoming a challenge especially in the third world states that rely on medical findings from the developed states. This study seeks to ascertain how promoter genes/regulators facilitate cancer angiogenesis, proliferation, progression, advocated medical procedures (1) and knowledge so far obtained by varied scholars who have specialized in this field. In their study, Rana Ajay and Chatterjee (3, p1) cite cancer tumors like any other body cells entail connection with other body tissues. This is to attain the necessary surviving nutrient materials in form of oxygen and food for their development as well as proliferation. Hence, prompting them to secrete cytokines essential in connecting them with endothelial cells, which are responsible for the enhancement of angiogenesis process (3, p1). However, recent studies have adopted the theory of an angiogenic switch control by ensuring equilibrium between pro- and antiangiogenic molecules that comprise tumor microenvironment (3, p1). In the event whereby proangiogenic overcomes antiangiogenic activity, tumor attains angiogenic phenotype (3). This enhances movement, proliferation and differentiation of endothelial cells into new vascular vessels whereby the latter comprise capillaries supposed to supply meant to necessary nutrients for survival. This mechanism entails vascular porosity induction leading to the formation of tissue odema as well as extravascular fabrin gel’s deposition (3). Hence, rendering numerous medical procedures meant to treat cancer ineffective due to the phenomenon’s complexity. This is because increased rate of tumor development as well as developing their respective capillaries enable them to have constant supply of the necessary materials meant for their proliferation. After attaining maximum size such that these tumors are unable to attain necessary materials because of their central organelles being far from the peripheral parts supplied by capillaries, they result to metastasis. Hence, multiplying to new forms of small tumors, which is a process that renders treating of cancer being ineffective and even complex (1). Spreading of Cancer comprises of four possible metastasis paths (4). They include lymphatic channels, blood vessels, body cavities besides transplantation (4). The latter route is extremely rampant during surgeries whereby transmittance encompasses localized tumors’ carriage by needles and other unsterilized surgical equipments. Hence, aiding in spreading of small tumors whereby at the place of their deposit (initiation stage), instigate capillaries’ network that will aid it to attain the necessary nutrient materials for development and survival as shown in Fig 1(5). If there is no inhibition process of interference in form of drugs administration, the process proceeds from promotion stage to other preceding steps, hence worsen victim’s state. This is because during surgery, whoever is undertaking the operation might be unaware whether he or she has played the role of spreading cancer tumors. Figure 1: How Angiogenesis complicates Cancer Once tumors are in isolation, they devise distinct survival tactics by releasing angiogenic structures essential in attracting both inflammatory and endothelial cells. Mainly, these structures undertake an indispensable role during promotion and progression stages, which is initiating vessels’ development supposed to avail required nutrients for survival. This is because tumors are not vascularized structures despite being in need of nutrients and channels through which they can excrete their respective metabolic waste, hence initiate network of vessel development. Afterwards, tumors grow beyond 2 mm3 critical size, whereby nutrients and other materials meant for cells’ development experience difficult in diffusing into their central organelles. Mainly, this leads to cellular hypoxia state thus representing tumoral angiogenesis onset. As depicted in Fig 1, increasing rate of new blood vessels development is an essential process responsible for tumor progression thus favoring hyperplasia to neoplasia transition (5). Transition in this case implies graduation from cellular duplication to a stage of unrestrained proliferation state, which is an attribute of tumor cells. Besides, Neovascularization (development of vessel network) enhances propagation of cancer cells throughout the entire body finally yielding to high metastasis potential. This is because the new developed blood vessels usually facilitate the spread of cancer cells to other distinct and far away organs, for instance, heart from the primary tumor. Based on Mandal (4) study, numerous cancer deaths currently in the world emanate from patients’ increased states of metastatic potential. This is because by the time of their respective diagnoses, new evidence states roughly 60% to 70% of those suffering from cancer confirm to have already undergoing metastatic process stage (4). Hence, entail prompt and effective treatment though currently in certain regions like in third world states, this may not be the case, which results to numerous deaths caused by cancer menace. Contrary to the above explained metastasis hypothesis, Stephen Paget over a century ago emerged with a different premise, which up to date majority of scholars have not readily accepted because of doubting its basis (7). In his argument, Paget put forth "seed and soil" premise (7) citing diverse organs pose varying responses to metastasis caused by primary tumors. This is because there are both diverse and numerous types of tumors, for instance, basal cell carcinoma; hardly extends in other parts (7). Paget’s premise argues that for cancer cells to spread, they ought to find appropriate and favorable sites outside of their respective prime suites (7). This is because these suites have similar characteristics (based on nutrients’ provision) to that of their parents’ sites, hence surviving is every easy compared to when invading strange body parts where they will devise new ways of survival. Paget’s hypothesis utilized breast cancer statistics with the intention of showing varying discrepancies especially when these types of cells choose to spread to other regions but remain passive in others. This is because they to other parts (7). Until the onset of 1970s when Dr. Judah Folkman emerged with a new strategy meant to put cancer into a remission, the world was still grappling with the menace’s increasing incidence (8). In his study that began as a revolutionary approach ended up being an area of scientific inquiry that has prompted medical field, devote its resources in unveiling numerous factors especially those relating to mechanisms that regulate angiogenesis and cancer progression (8). Since, Folkman’s invention and publication of his idea of inhibiting angiogenesis as a new effective way of dealing with cancer menace, numerous medical scholars have currently come up with concrete scientific backing of “anti-angiogenesis” (9). Hence, cite “anti-angiogenesis” as the most effective remedy for cancer menace that has not only caused numerous deaths globally but also prompted states to incur heightened medical expenses. The premise behind this therapeutic encompasses cutting supply of the necessary nutrients materials essential for tumor cells’ survival and progression. This is because similar to other body cells, tumors entail nutrients to survive evident from the way they normally initiate development of vascularization (5). Therefore, Folkman argued that, the effective starving of tumors was the only way to put cancer at bay by doing away with their respective blood supply channels. Up to date, this premise has raised more interests besides being the center of study by numerous scholars terming Folkman’s premise as a breakthrough that would save numerous lives globally because it has already worked with varied cancer infected mice during experiments so far undertaken (9). Some of the main three proposed antiangiogenic compounds though still under scrutiny in US labs besides some incorporated in combating cancer embrace angiostatin, endostatin and vasculastatin (9). The feasibility of these compounds has prompted medical practitioners to come up with appropriate procedures meant to tackle cancer menace based on its severity. For instance, Albini, Tosetti, Li Noonan and Li (1) in their study cite four levels on how to mitigate cancer severity among patients as indicated in the Table 1. Table 1: Cancer Treatment Levels based on its severity on victims Level of approach Severity of the patient Level I For healthy people; early stage intervention after diagnosis. Level II Patients having conditions characterized by heightened cancer risks. Level III Treating preneoplastic lesions Level IV It encompasses prevention of any overt cancer reappearance. However, the treatment of cancer despite comprising of angiogenesis suppression, medical interventions should not result to disrupting healthy endothelial functions essential for wounds’ or tissue healing. Therefore, this entails keen titration, which has turned to the current medical field’s puzzle despite having unveiled an indispensable breakthrough. This is because respective drugs’ formulators ought to ensure whatever they produce is of higher value and benefits the ailing than the former used chemotherapy or radiotherapy options (1). Currently, due to some inadequacies practitioners have ended up advocating incorporation of former chemotherapy option with modern produced cancer pathways (2). This is evident especially in the treatment of bladder cancer with VEGF pathway known to give enhanced effects compared when administered alone (1, p 47). VEGF pathway has several family members having specialized functions based on the part of the body (6). They range from VEGF-A to D besides placental growth aspect (6, p 334). Besides VEGF family drugs, current studies have also unveiled and ascertained the feasibility of Neovastat as an effective remedy for cancer. This drug compared to others is naturally occurring substance commonly obtained from dogfish shark’s spine and administered orally (10, p 624). The inception of using this drug as a remedy was a trial experiment supposed to affirm claims its source acted as an effective supplement meant for people suffering from cancer- related predicaments. After intensive scrutiny, scholars confirmed lay people’s claims, hence leading to its current advancements whereby it comprises one of the most effective drugs utilized in combating cancer malady (10). Neovastat in its quest to combat cancer malady, it has two essential mechanisms including; Degradative Matrix Metalloproteinases prevention Sealing of receptor sites for VEGF responsible for shunning endothelial cells from; 1. Proliferating 2. Migrating 3. Organizing to create new blood vessels in Vitro Studies contacted so far concerning Neovastat remedy have indicated benefit of 16.3 months survival when administered with high doses contrary to 7.1 months who received lower amounts (10, p 624). Hence, proving to be effective and comprising of almost zero side effects especially when administered to people experiencing renal cell cancer. Pre-clinical studies have also indicated practitioners can utilize it either alone or combine with other remedies and still offer commendable results due to its low level of toxicity. Conclusion Angiogenesis besides known to enhance the survival of human body cells, it acts as an essential role confirmed by medical studies responsible for proliferation, progression and spreading of cancer cells (1). Hence, rendering the process of combating cancer being an extremely complex task especially to the medical practitioners before Folkman came up with his mode of combating proliferation of tumor cells in 1970s (8). Folkman’s act acted as a medical breakthrough that prompted numerous experts both practitioners and other scholars of related fielded having interest on how to terminate the supply of blood to deny cancer cells the necessary food materials for their development. Consequently, this study led to antiangiogenis premise that comprised of formulating varied agents supposed to combat cancer cells when alone or incorporated with other substances (9). However, studies are still ongoing with the recent Neovastat drug discovered whose side effects among t renal cell cancer patients is insignificant compared to other proposed agents still in the market but effective when incorporated with chemotherapy (1). References (1) Albini A, Tosetti F, Li VW, Noonan DM, Li WW. Cancer prevention by targeting angiogenesis. Nature Reviews. Clinical Oncology 2012 09; 9 (9):498-509. (2) Elfiky A, Rosenberg J. Targeting angiogenesis in bladder cancer. Current Oncology Reports [serial on the Internet]. (2009, May), [cited September 21, 2013]; 11(3): 244-249. Available from: MEDLINE Complete. (3) Rana B, Ajay R, Chatterjee, M. Angiogenesis & therapeutic targets in cancer. [S.l.]: Bentham e Books, 2010. (4) Mandal A. Metastasis - What is Metastasis? [Internet]. News Medical; 2009[21 September 2009; Cited 21 September 2013]. Available from http://www.news-medical.net/health/Metastasis-What-is-Metastasis.aspx (5) Agio World. How Angiogenesis complicates Cancer. [Image on the internet]. n.d. [21 September 2013] http://www.angioworld.com/images/inhhibition.jpg (6) Ellis LM, Teicher BA. Antiangiogenic agents in cancer therapy. Totowa: Humana Press, 2008. (7) Fidler, I. J., & Poste, G. (2008). The "seed and soil" hypothesis revisited. Lancet Oncology, 9(8), 808. Retrieved from http://search.proquest.com/docview/200948910?accountid=458 (8) Ribatti, D. (2008). Judah Folkman, a pioneer in the study of angiogenesis. Angiogenesis, 11(1), 3-10. DOI:http://dx.doi.org/10.1007/s10456-008-9092-6 (9) Barry SA, Almeida CA. Cancer: Basic Science and Clinical Aspects. Hoboken, New Jersey: John Wiley & Sons, 2011. (10) Willkes GM. 2013 oncology nursing drug handbook. Sudbury: Jones & bartlett learning, 2012. Read More