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This writer sees cancer prevention as the most effective of all anti- cancer strategies, especially those strategies which target cell growth, differentiation, and apoptosis. Phyto-prevention—the use of natural derived compounds often called phytochemicals, along with a multi-faceted molecular targeting approach—in particular, shows great promise. It is important to note, however, that drawing clear lines between natural medicines and remedies, on the one hand, and ‘drugs’ or pharmaceutical products, on the other, can often be wrought with confusion, since many drugs are derived from the natural components of plants. Nevertheless, most natural components of plants are seen as less aggressive forms of therapeutic intervention than chemicals.

The principle phytochemicals that have been identified as most useful for cancer prevention strategies are organosulfurs, phenols, glucosinolates, saponin. Closely related to phytochemical strategies are those strategies that include the use of micronutrients such as NSAIDs and Vitamings A, C, D, E, folate, calcium and selenium are considered—all of which are often referred to as “chemopreventive.” Perhaps the greatest level of success at fighting cancer through nutrition is found in the battle against colon-rectal cancer (CRC), as we now know that almost 50% of CRCs can be prevented by proper nutrition.

The presence of gastrointestinal homeostasis or health disruption depends on the extent to which natural compounds are successful at mediating the effects of toxic elements and stress which lead to a dysregulation of the defense mechanisms and chronic inflammation. One of the most prominent and challenging aspects of our study of cancer prevention lies in identification of people who are at risk for CRC.  There are many bio-markers for CRC such as K-ras, p53, APC mutation, COX2, DNA methylation and DNA strand breaks, as well as apoptosis and ACF which are also correlated with CRC. A reduced risk of CRC of up to 90% for subjects taking NSAIDs and Asprin has been demonstrated in patients with sporadic colorectal neoplasia according to a case control study and a cohort study.

Pharmokokinetics and pharmacodynamics are equally if not more complex with respect to plant extracts and food derived products as they are for chemical agents. Much of the discussion so far has centered around Curcumin and tea, two natural products that have been singled out for the prevention and treatment of CRC. Curcumin is a cancer preventive polyphenolic derivative of turmeric isolated from Curcuma longa with an anti oxidant property which inhibits cell growth and proliferation and increases apoptosis. Curcumin supplementation was found to decrease colonic ACF formation down to 45% in AOM treated rats. Green tea and black tea contain polyphenols with abundant catechin, EGCG in green tea and Theaflavin (TF-1-2-3) in black tea.

Epidemiological studies using dietary surveys have shown conflicting results in the correlation between tea consumption and CRC risk. In a study conducted in the Netherlands no association was observed between black tea consumption and the inhibition of ACF formations. In vitro and animal studies have suggested, however, that EGCG does inhibit tumor growth; it has been found to be effective for mitigating microvessel density, tumor cell proliferation, and vascular endothelial growth factors, along with angiogenesis and matrix metalloproteinase. Many argue that whole food extracts from a variety of natural products are more effective at preventing cancer than purified micronutrients. With respect to tea, however, most of the epidemiological data suggest that purified tea components are even more effective than tea in its natural form.

There are numerous agents under evaluation through rigorous clinical trials for the prevention of CRC, including lycopene, rumenic, butyrate, resveratrol, soy, S-allylmercaptocysteine from garlic and sulindac. Nevertheless, it is very difficult to prove the efficacy of these natural products in a conclusive fashion, and comparing their effectiveness with that of chemical agents is equally if not more complex and challenging. Conflicting epidemiological reports on the alleged cancer preventive property of tea, for example, suggest the way in which surveys concerning the use of natural products have limited value. 

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As a specialist in the area of diversity, I find particular joy in helping to foster the representation of all ethnicities in our medical institutions. I think it is not only healthy for America to have a medical staff that was born all over the world, but it is also healthy for the planet. Over the course of the last 20 years, I have helped hundreds of residency applicants struggling to write their own statement in English as a second or foreign language, something that can be enormously difficult. You need a very well written, eloquent statement in order to be accepted. Much of your competition uses professional help, which gives them an edge. It would be prudent for you to get help as well.

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I have invested well over a decade in researching what makes the personal statement for medical residency or fellowship as effective as possible - particularly in the area of Oncology. I invite you to fill out my Online Interview Form and send me your CV and/or rough draft for a free

Loyola’s Hematology/Oncology Fellowship Program. The goal of Loyola’s fellowship program is to train academic leaders in hematology and oncology, to advance the science of the discipline, and provide meaningful education and outstanding clinical care. Loy

An old wise man and creative writer, I help doctors from all over the world to be selected for residency and fellowship positions. For as many doctors as possible, I draft a model first paragraph for your residency or fellowship Statement at no obligation. My service is quite different from other statement writing services on the Internet for several reasons. I am the little guy on the web, not a big business like most of my competitors. You deal directly with me. I answer all of your questions completely free of charge and I am solely responsible for producing a statement that you are very pleased with. 

The Hitchcock-Wilson Fellowship in Hematology, Oncology and Bone Marrow Transplant. The program is ACGME accredited and provides a broad range of experience in hematology, oncology and stem cell transplant. It provides fellows with a strong clinical balan

Wnt & Notch

Since natural prevention strategies appear to be more effective against colon cancer than they are against other cancers, this review focuses on the colon as the most promising target of anti-cancer and cancer prevention strategies. The colon is a complicated tissue comprised of millions of test-tube-shaped structures called crypts. The gastrointestinal epithelium cells homeostasis maintenance is reflected through cell birth, migration and death (Kershaw, Byrne et al. 2013). Colon cancer initiates with the formation of polyp-like outgrowths of the tissue as a result of genetic profile or the disruption of subcellular signaling pathways in the crypt.

Most cancer cells share 10 common characteristics as summarized by Hanahan and Weinberg, sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, deregulating cellular energetics, avoiding immune destruction, tumor promoting inflammation, and genome instability & mutation (Kershaw, Byrne et al. 2013). Aberrant cells such as cancer cells have been biochemically dysregulated as a result of genetic mutations. Main subcellular mechanisms leading to CRC are the Wnt signaling pathway, the Notch signaling pathway, the NF-kB pathway, PI3 K/Akt, the transforming growth factor (TGF)-b, and the Ras-MAPK signaling pathway.

A broad canon of work including mathematical and computational analyses has been conducted in an effort to better understand CRC initiation and development. Studies have identified a mutation in Smad involved in TGF signaling as a key event in CRC progression (Gerstung, Baudis et al. 2009). Other results suggest that colorectal tumuorgenesis initiates with a loss of APC involved in Wnt signaling, followed with one KRAS mutation and TP53 inactivation. Multi scale modeling, a mathematical approach which addresses the interplay between various hallmarks of cancer, suggests that the sustained proliferative signaling of CRC cells through cell cycle control plays an important role in many cancers including CRC (Kershaw, Byrne et al. 2013).

As shown in table #x, 70% of all subcellular signaling pathways contributing to CRC fall under the category of sustained proliferative cancer.

Drug design for effective cancer prevention requires the development of agents with specific therapeutic effects that occur during a certain window period that exists between normal vs. cancer stem cells (CSCs). Here, therefore, I review several natural agents and their effects on different signaling pathways followed by a discussion of which agent or combinatorial treatment is best suited for therapy or prevention, according to different stages of SC and CRCs, in an effort to enhance effectiveness through the personalization of treatments.

Wnt Signaling Pathway

The Wnt signaling pathway is present in the animal kingdom and plays multiple important roles such as stem cell maintenance, cell proliferation, differentiation, and apoptosis. The homeostasis state of the crypt is mostly controlled through the β-catenin in the wnt signaling pathway. Wnt target genes are c-Myc, Axin2 and ASCL. The transcription factor (TF) ASCL restricted to crypt plays a significant role in stem cell maintenance. Disruption of the Wnt signaling pathway via ASCL2 leads to hyperplasia and loss of the stem cell compartment (van der Flier, van Gijn et al. 2009). The critical initiating steps in malignant transformation are inactivation of the APC gene and activating mutations of β-catenin, which is reported in almost all CRCs (de Sousa, Vermeulen et al. 2011). Current clinical studies and drug development approaches for the Wnt signaling pathway fall into two principal categories, first a direct targeting approach of Wnt signaling pathway compartments and, second, an indirect targeting approach of the cascade.

Two inhibitors of this pathway have been identified by Chen and colleagues in 2009. One molecule disrupted wnt production and secretion and the second served to stabilize Axin2 to target β-catenin in APC mutated CRCs. Axin 2 is part of the β-catenin destruction box and Poly ADP-ribosylating enzymes tankyrase1 and 2 (TNKS) degrades Axin2; this enzyme has also been noted as having potential therapeutic utility. A great target for epigenetic modulators of the canonical pathway is secreted Fzd-related proteins (SFRP), since hypermethylation of this gene is implicated in CRC. Another potential area of benefit surrounding is the transcription factor, TCF/β-Catenin, which disrupts cell growth in vitro. Emami and colleagues discovered a leading compound, ICG-001, which targets the CBP/P300 co-activator of TF TCF. The role of the Wnt signaling pathway in cell homeostasis, however, suggests that the direct targeting strategy may be associated with adverse side effects. So, it is important to note the importance of the compounds’ specific therapeutic effects within a specific time frame, for our purposes with respect to CRC prevention, preventing the transformation of normal stem cells (SC) into CSCs (de Sousa, Vermeulen et al. 2011). The indirect approach simply aims to target Wnt signaling target genes like Cox2.

UK PGY2 Residency – Hematology:Oncology. Residents gain advanced knowledge in general hematology/oncology, bone marrow transplantation, pediatric hematology/oncology, gynecology/oncology, and ambulatory care. The primary emphasis of the hematology/oncolog