Search This Blog

Friday, August 31, 2012

Aloe Vera Plant Benefits

Aloe Vera is a succulent plant known for its healing, medicinal properties. For topical use, the leaf is sliced open and the pulp from within is used for application. Among the many forms it is used in, aloe vera juice and aloe vera gel are the most popular. Aloe Vera is often considered a wonder plant, and people claim its assistance in curing just about any ailment.
 


Aloe vera plant has the capacity to treat following ailments:

Constipation: Constipation is treated with orally consumed dried latex that is taken from the inner lining of aloe leaves. The laxative properties of a substance called aloin contained in the aloe vera plant, is supported by scientific evidence. A large number of herbal remedies that treat constipation contain aloe vera extracts.

Genital herpes: A few studies have suggested that Aloe vera extracts in a hydrophilic cream may be effective in treating genital herpes in men. This combination is believed to work better than aloe gel or a placebo.

Psoriasis vulgaris: The initial evidence suggests that psoriasis vulgaris may be effectively treated with an extract from aloe in the form of a hydrophilic cream. However, it is strongly recommended against it as additional research is needed in this area.

Seborrheic dermatitis: Seborrheic dermatitis causes stubborn dandruff and the skin on the scalp to become inflamed, scaly and itchy. Aloe vera lotion may be an effective treatment, according to initial studies.

Cancer prevention: Evidence suggests that aloe consumed orally may reduce the risk of developing lung cancer. However, it is unclear if it is the aloe itself or other factors that may provide this benefit.

Dry skin: Aloe vera plant health benefits have been extolled for decades. The moisturizing qualities of aloe, and its consequent capacity to effectively reduce skin dryness are backed by early, low-quality scientific evidence. To be sure of its healing powers, higher quality studies are required.

Lichen planus: This common skin disease results in an itchy, swollen rash on the skin or in the mouth. The scientific evidence suggesting that aloe may be a safe, helpful treatment for lichen planus, is limited. There is need for additional research.

Skin burns: Initial evidence form scientific investigations suggest that aloe may assist the healing of mild to moderate skin burns. Additional proof is required to confirm this fact.

Skin ulcers: Among the aloe vera benefits for skin is the likelihood of its ability to help heal skin ulcers with local application. These conclusions have been arrived at through early studies, which still leaves the need for high-quality studies comparing aloe alone with placebos.

Ulcerative colitis: While research regarding benefits of aloe vera in treating ulcerative colitis (UC) is limited, nonetheless, the results are promising. It is yet to be understood how aloe vera measures up to other treatments used for UC.

Wound healing: The results on aloe vera's wound healing properties are conflicting. While some studies say that it has a positive effect, others report that there are no improvements, and at times potential worsening of the condition. Further study is required to establish its exact effect.

Among the other therapeutic uses of aloe vera, it is said to sooth skin irritation caused by prolonged exposure to the sun's radiation. There is insufficient evidence to support claims of the use of aloe vera to treat mucositis, diabetes and HIV infection. Aloe vera juice benefits are often advertised with regards to treating heartburn and irritable bowel syndrome. It is also common practice for cosmetic companies to include extacts from Aloe vera in their products. While aloe vera plant proves to be extremely beneficial for the hair and the skin, to truly harness its powers, it is important to know how to use the plant. It is the transparent fluid exuded by the inner leaf wherever it is cut or crushed, that must be applied to the hair or skin, for it is this substance that is said to have soothing, moisturizing properties.

Aloe Vera for Cancer Treatment

Introduction
 
Aloe Vera is a soothing and sanative herbal medicine. Indigenous to West Africa, it is cultivated all over the world for its medicinal usefulness where it's used mostly for the treatment of skin diseases.
 
The herb aloe has more than 300 species, but the best known of them all is the 'Aloe Vera'. It is a short, stemless succulent plant with thick and fleshy stems. For the purpose of healing, it's used both internally and externally. Chemical compounds such as lectins, acemannan, polysaccharides and anthraquinones along with vitamin C, amino acids, germanium etc., make aloe vera very useful in the maintaining and toning of dry skin, repairing of blood vessels, liver, stomach, and kidney, and treat various disorders like diverticulitis, ulcers, asthma, and heartburn. It also helps in healing cuts and wounds. Many researchers claim that it has the power to help cure HIV/AIDS. However, recent research shows that it can also be used for the treatment of cancer too.
 

Aloe Vera and Cancer
Corrosion causes damage to the genes. These adducts multiply themselves in a cell (mitosis) and possess the power to damage that cell permanently. They are not initially recognized by the immune system. Hence, they keep on dividing in each cell and the possibility of cancer increases. At the time of mitosis, the cells make the same adducts. This is how cancer cells are produced. Though all the cells, except the nerve cells from the central nervous system, need to get replaced, it becomes impossible for the healthy neighboring cells to grow. Once the cancer turns malignant, it conquers the whole body of the host. This ability makes cancer the most life-threatening disease of them all. However, early detection of the disease combined with proper nourishment of the patient will help the person overcome the condition. This nourishment is done by growing the cells in a controlled body environment. This is termed as 'tissue culture'. Cancer treatment therapy, called 'Chemotherapy', entails a close examination of the cells. If found infected, they are killed immediately.

Aloe vera is proven to be useful in the treatment of cancer patients, for whom chemotherapy doesn't work. As it contains a little amount of the cancer-healing substance, it works its magic when used in conjunction with chemotherapy. Also said to have a good effect on the blood, aloe vera helps the absorption of vitamin-C and antioxidants, that's why it is speculated that it will increase the effectiveness of anti-cancer herbs.

How does it Help During Chemo?
The question frequently asked is does chemo really cure the patient of cancer? The answer often is Yes! However, at what price does the tumor vanish, doesn't the health and spirit of the patient itself also seem to vanish. So are we really treating the patient or are we treating just the tumor? More often than not it's the latter. Chemotherapy can't differentiate between the damaged and the healthy cells. So, healing from cancer as well as the chemotherapy, both become essential. The radiation from chemotherapy are sometimes too toxic for patients to survive. Aloe vera works as a soothing agent in patients undergoing the therapy. That's why alternative therapies always act as support medicines to enable the patient live through the rigorous chemotherapy sessions.

Effects on the Immune System
The presence of cancer according to some people suggests a weak immune system, because it is not able to react to the new growth of cells that it should ideally perceive as a threat due to their un-natural foreign nature. Hence, aloe vera works on the immune system in great degrees making it stronger so that it can eat away the cancerous cells. The unique mixture of aloe vera in aloeride works as the best cancer suppressor. It prevents cancer by suppressing the tumor causing cells. The aloeride is made up of aloe barbarensis miller, that has the same medical characteristics as the Aloe vera plant.

Besides enriching the immune system aloe vera is also a great detoxifier. The acemannan present in it promotes the production of lymphocytes and helper cells which prevent the infection from spreading to the healthy cells. The herb slows down the growth of cancerous tumors, as it contains lectins and emodines, which are two tumor resistant chemicals. It actually checks the growth of malignant tumors and also provides a soothing effect in patients suffering from skin cancer.

Availability
Aloe vera is not always used in its direct form, but also in the various forms available in the market, such as - gels, capsules, creams, and drinks (the most popular being filleting the flesh, removing the skin, and then blending the pulp to make it drinkable). All these products are chemically tested and certainly prove beneficial for the treatment of cancer. Though, aloe vera gels and creams are most popular.

Aloe Vera Juice
A regular intake of aloe vera juice helps to prevent the production of cancer cells in the body. For patients already suffering from cancer, it soothes intoxication caused by radiotherapy. The juice has proved helpful in healing many types of cancers, including breast cancer, ovarian cancer and blood cancer (leukemia).

Besides that it also helps the digestive tract function normally, which is a very important part of the human body and is responsible for a major portion of medical conditions that people experience. Basically, aloe vera proves useful in healing the side effects caused by chemotherapy and radiotherapy. Being a great anti-inflammatory it could indirectly help our body experience less stress while the anti-cancer treatment is underway, which as mentioned earlier is one of the greatest ordeals that is faced by a patient with cancer.

Aloe Vera Creams
These creams are odorless and are best used to reduce the itchiness of the skin in psoriasis (a type of skin cancer). It also protects the skin from the damage caused by the exposure of the skin to the ultraviolet rays, that are very harmful for cancer patients.

What we must understand though, is the amount of aloe vera extract that should be used. Aloe vera, though clinically tested, does contain a few substances that do not agree with a few people resulting in a few serious side effects like hepatitis, diarrhea, stomach pain, nausea, problems in blood clotting, thyroid problems and so on. You need to remember that the herb acts best as a supporting medicine and not as the sole cure for cancer. In conjunction with the proper treatment of cancer, it helps the body to receive the treatment better and improve on its effectiveness. However, you need to first check with your physician before starting out on an aloe vera supplement.

Friday, April 27, 2012

Colon cancer stem cells


Colorectal cancer (CRC) is the third most common form of cancer and the second cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns, leading to 655,000 deaths worldwide per year (1). Despite the emergence of new targeted agents and the use of various therapeutic combinations, none of the treatment options available is curative in patients with advanced cancer. A growing body of evidence is increasingly supporting the idea that human cancers can be considered as a stem cell disease. According to the cancer stem cell model, malignancies originate from a small fraction of cancer cells that show self-renewal and pluripotency and are capable of initiating and sustaining tumor growth (2).
        This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy. First, we will briefly revise the knowledge available on normal intestinal stem cells and recent advances in understanding crypt biology, which have led to new theory on the origins of colon adenomas and cancers. Then, we will summarize the evidence and current status on colon cancer stem cells, focusing on their relevance and promises for the treatment of colorectal carcinoma.

Colonic stem cell identification
The adult colonic epithelium has a well-defined architecture organized into crypts, dynamic structures which are constantly self-renewing (3). Each crypt unit is maintained by adult multipotent stem cells (SCs), located at the bottom of the structure itself, that are able to simultaneously self-renew and generate a population of transiently amplifying cells which in turn generate more the specialized intestinal epithelial mature cells. Three differentiated cell types mediate the function of colonic epithelium: the colonocytes, also termed absorptive enterocytes, the mucus-secreting goblet cells and the hormone-secreting enteroendocrine cells (Figure 1).
         Adult SCs are defined by several key functional properties including: self-renewal, potential for multilineage differentiation and tissue regeneration. Two different models have been proposed to localize the intestinal SCs; the “+4 position” model and the “stem cell zone” model (4). According to the former, the intestinal SCs are located at the +4 position relative to the bottom of the small intestine crypt, just above the non-cycling Paneth cells. These cells are quiescent, slowly cycling, label retaining cells (LRCs) and, through asymmetric division, give rise to their differentiated progeny. The more recent “stem cell zone” model states that active, rapidly cycling cells and self-renewal, termed crypt base columnar (CBC) cells, are the true intestinal SCs (Figure 2). These cells are interspersed between the Paneth cells in the small intestine or located at the very bottom of the crypt in the colon. The intestinal stem cells, both +4 cells and CBC stem cells give rise to the transitamplifying population that undergoes vigorous division and differentiation into enterocytes, goblet cells, and enteroendocrine cells as they migrate out of the crypt onto the villi (3).




Fig. 1. Colonic crypt organization. a. In the epithelial lining of normal colonic mucosa, stem cells (red) are located at the bottom of the crypts. Upon asymmetrical divisions, the daughter cells undergoing differentiation migrate upward to give rise in turns to transitamplifying (TA) precursors (light blue) and terminally differentiated cells (pink). b. Cell types in the colon epithelium. Intestinal stem cells generate three epithelial cell types: the absorptive columnar cells, the hormone-producing enteroendocrine cells, and the mucous-producing goblet cells.




Fig. 2. Models for stem cells location of stem cells in intestinal crypts. a. The “+4 position” model suggests that intestinal stem cells are quiescent, slowly cycling cells and  located just above the Paneth cells at position +4 relative to the crypt bottom (green). The most important marker that identifies these cells is Bmi-1. b. The “stem cell zone” model assumes active, rapidly cycling cells, so-called crypt base columnar (CBC) cells (red), interspersed with Paneth cells, are the true intestinal stem cells. The most important marker to identify these cells is Lgr5.
The Lgr5 gene encodes a leucine-rich repeat containing G-protein coupled receptor, also known as Gpr49. Lgr5 expression is restricted to cycling CBC cells and it has been demonstrated that Lgr5-expressing cells differentiate into the expected functional lineages of the colonic epithelium (5). Transcriptome analysis of Lgr5+ epithelial cells isolated from the bottom of the small intestinal crypts led to the identification of a gene signature for these Lgr5+ SCs. The OLFM-4 gene encodes a secreted molecule with unknown function, originally cloned from human myeloblasts (6), which is enriched in human colon crypts (7). Due to the very low expression levels of Lgr5, OLFM-4 has been recently proposed as a more faithful SC marker highly expressed in CBC cells in human small intestine and colon (8).

Colorectal cancer stem cell identification
Tumors are composed of a heterogeneous mixture of cancer cells at various levels of differentiation, very similar to the structure of an organ. Recently, the “cancer stem cell” model of tumorigenesis has proposed that within the tumor mass there is a predetermined cell population with a ‘‘stem cell’’ phenotype, able to perpetuate the cancer, while the rest of the tumor cells are incapable of self-renewal (9). Even though it has long been assumed that mutations within adult colonic stem cells may induce neoplastic transformation, the proof of existence of colorectal cancer stem cells (CRC-SCs) has been hindered in the past years by difficulties in identifying a specific biomarker for this rare cell population. Only recently, new evidence has been provided that supports the existence of CRC-SCs, confirming that the tumorigenic cell population of CRC can be isolated on the basis of the expression of specific cell surface biomarkers (9). The standard analysis to ascertain the existence of a subpopulation of cancer stem cells (CSCs) is the demonstration that these cells can transfer the tumor in immunocompromised mice and replicate the phenotypic heterogeneity of the parental tumor. Several recent studies have evaluated the functionality of specific CRC-SC biomarkers by using a combination of flow cytometry to identify a “putative” SC population and xenograft models involving immunodeficient mice to determine their tumor initiating potential (9).
In the first two studies, CD133, also known as Prominin-1, was employed to identify the tumorigenic cell population within CRC and metastatic (10, 11). When transplanted into the renal capsule of NOD/SCID mice, CD133+ cells readily developed tumors displaying morphologic features equivalent to those of the parental cancer. Tumor phenotype was further maintained upon serial transplantation (10). Similarly, in the second study, a population of CD133+ cells, accounting for approximately 2.5% of tumor cells, was isolated from colon cancer specimens and perpetuated in vitro as floating colonies or “tumor spheres” (11). CD133+ cells readily gave rise to tumors in mice, whereas the CD133 cell population was unable to generate tumors even after serial transplantation in mice (9). Both studies demonstrated the expression of CD133 also in normal colon tissue, although at a lower frequency, reinforcing the hypothesis that CD133+ CRC-initiating cells in cancer samples might result from oncogenic transformation of normal colonic SCs.
Subsequently, one study proposed CD44 and the epithelial surface antigen (EpCAM) as CRC-SC-specific markers, with further enrichment by CD166. Purified CD44+/Ep- CAMHIGH cells injected into NOD/SCID mice resulted in high frequency generation of tumor xenograft. In contrast, CD44-/EpCAMLOW cells lack tumor initiating activity (12). Further subfractionation of the CD44+/EpCAMHIGH cell population by using the mesenchymal stem cell marker CD166 increased the success of tumor xenograft.
Finally, in a more recent study, aldehyde dehydrogenase 1 (ALDH) has been proposed as a promising new marker for normal and malignant human colonic SCs (13). Flow cytometric isolation of ALDH1+ cancer cells and implantation of as few as 25 cells in NOD/SCID mice generate tumor xenografts. Further isolation of cancer cells using a second marker (CD44 or CD133 serially) only modestly increased enrichment based on tumor-initiating ability.
In an another study, reported that in primary colon cancer samples from humans and mice, CD133 was expressed in all epithelial, EpCAM+ cells in the malignant tissue and that CD133 expression was excluded from the non-epithelial cell components of the tumor (14). Thus, they proposed that the inability of CD133- to generate tumors could be simply due to their non-epithelial nature. Furthermore, the same authors demonstrated that both, CD133+/EpCAM+ and CD133-/EpCAM+ cell populations, isolated from liver metastasis of colon cancer, were able to generate tumors upon serial transplantation into NOD/SCID mice (14).
A comparison of expression of the three markers CD133, CD44 and CD166 that have been associated with CRC-SCs revealed that the expression of CD133 correlates with that of CD166, whereas both do not correlate with CD44, confirming that CD133 is, alone, the best marker to predict poor patient survival (15).
Identification of biomarkers for CRC-SCs will improve the understanding of the mechanism underlying tumor growth and progression. Once again, studies performed on mouse model could offer helpful suggestion. Recently, one study provided a very convincing demonstration of the origin of intestinal cancer from Lgr5+ CBC cells. The authors have shown that deletion of APC in Lgr5+ expressing cells leads to their transformation within days, suggesting that Lgr5 may mark not only normal intestinal stem cells, but also a limited population of CSCs (16). Simultaneously, using knock-in LacZ reporter mice within the Prominin-1 (Prom1) locus, in a study have shown that Prom1+ cells, located at the base of the crypts in the small intestine, co-express Lgr5, generate the entire intestinal epithelium and are susceptible to neoplastic transformation (17).
From a clinical point of view, a recent study showed that Lgr5 was markedly over-expressed in the majority of advanced CRCs compared with normal mucosal tissue (18). As expected, in situ hybridization analysis confirmed the expression of Lgr5 in CBC cells in both small intestine and colon. This Lgr5 expression, which was variable among CRC cases, correlated significantly with lymphatic and vascular invasion, lymph node metastasis and tumor stage, suggesting the involvement of this marker in tumor progression.
It might be summarized the markers that have been used to isolate CRC-ICs, shown in table 1 (9).

Table 1 Markers that have been proposed to characterize normal intestinal SCs and used to isolate CRC-ICs

Marker
Function
Normal intestinal stem cells
Musashi-1
RNA-binding protein
Hes-1
Transcriptional repressor
EphB receptors
Cell surface receptors
Bmi-1
Policomb-repressor protein
Lgr5
Unknown, WNT target gene
Aldh-1
Enzyme
Colon cancer stem cells
CD133
Unknown
CD44
Hyaluronic acid receptor
CD166
Adhesion molecule
Aldh-1
Enzyme


Clinical implications of colorectal cancer stem cells
The CSC model has important implications for cancer therapy. At present, anticancer therapies for CRC include surgery, radiation, chemotherapy, and anti-VEGF or EGFR monoclonal antibodies. In most cases, many current cancer therapies target the most rapidly dividing cells, which represent the majority of the tumor cell population. Similarly, CRC-SCs have been found to be enriched in colon tumors following classical chemotherapeutic regimens and remain capable of rapidly regenerating tumor from which they were derived (19). The authors have further demonstrated that resistance is mediated, at least in part, by ALDH1 enzyme activity.
Together with resistance to chemotherapy, CSCs are frequently resistant to standard radiotherapy regimens. In this respect, it has been recently demonstrated that resistance to radiation of CD133+ glioblastoma SCs can result from elevated expression of DNA damage response genes (20). Radiotherapy for glioblastoma is associated with an increase in the proportion of the CD133+ fraction.
In another study, has recently demonstrated that the up-regulation of interleukin-4 (IL-4) in CD133+ CRC-SCs is an important mechanism that protects these tumorigenic cells from apoptosis. CD133+ CRC-SCs produce IL-4 as an autocrine growth factor promoting tumor resistance to chemotherapeutic agents such as 5-fluorouracil and oxaliplatin (21). This phenomenon was confirmed in xenografts in which the administration of anti- IL-4 antibodies significantly reduced tumor growth after chemotherapy.
In a recent study, generated CD133+ tumor sphere cultures from several colon cancer specimens and performed mass-spectrometry-based quantitative proteomics in order to identify cell surface proteins enriched on culture tumor cells (22). These cells retain the expression of cell surface markers such as CD133, CD166, CD44 and EpCAM as well as other stem cell-associated proteins including nestin, Bmi1 and Msi-1, thus confirming the value of this in vitro model for biological analysis of CSC populations as well as for drug screening experiments.

Conclusion
Increasing evidence shows that CRC-SCs may play a critical role in tumor development and progression. CRC-SC resistance to conventional therapies may explain why it is difficult to completely eradicate cancer and why recurrence is often inevitable. Thus, the identification and molecular characterization of CSCs is critical to develop therapeutic strategies that specifically target this rare population of cells and that are likely to be effective in eradicating tumors and in reducing the risk of relapse and metastasis.



 References
1.     Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics. CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30.
2.     Boman BM, Wicha MS. Cancer stem cells: a step toward the cure. J Clin Oncol. 2008 Jun 10;26(17):2795-9.
3.     Radtke F, Clevers H. Self-renewal and cancer of the gut: two sides of a coin. Science 2005; 307: 1904-09.
4.     Barker N, van de Wetering M, Clevers H. The intestinal stem cell. Genes Dev 2008; 22: 1856-64.
5.     Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007; 449: 1003-07.
6.     Van der Flier LG, van Gijn ME, Hatzis P, Kujala P, Haegebarth A, Stange DE, Begthel H, van den Born M, Guryev V, Oving I, van Es JH, Barker N, Peters PJ, van de Wetering M, Clevers H. Transcription factor achaete scute-like 2 controlsintestinal stem cell fate. Cell 2009; 136: 903-12.
7.     Kosinski C, Li VS, Chan AS, Zhang J, Ho C, Tsui WY, Chan TL, Mifflin RC, Powell DW, Yuen ST, Leung SY, Chen X. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Natl Acad Sci USA 2007; 104: 15418-23.
8.     Van der Flier LG, Haegebarth A, Stange DE, van de Wetering M, Clevers H. OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology 2009; 137: 15-17.
9.     Ricci-Vitiani L, Fabrizi E, Palio E, De Maria R. Colon cancer stem cells. J Mol Med 2009; 87: 1097-104.
10.  O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007; 445: 106-10.
11.  Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R. Identification and expansion of human colon-cancer-initiating cells. Nature 2007; 445: 111-15.
12.  Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 2007; 104: 10158-163.
13.  Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS, Boman BM. Aldehyde de-hydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res 2009; 69: 3382-89.
14.  Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T,et. al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest 2008; 118: 2111-20.
15.  Horst D, Kriegl L, Engel J, Kirchner T, Jung A. Prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer. Cancer Invest 2009; 27: 844-50.
16.  Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, et.al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 2009; 457: 608-11.
17.  Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, Poppleton H, Zakharenko S, Ellison DW, Gilbertson RJ. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 2009; 457: 603-07.
18.  Uchida H, Yamazaki K, Fukuma M, Yamada T, Hayashida T, Hasegawa H, Kitajima M, Kitagawa Y, Sakamoto M. Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer. Cancer Sci 2010; Epub ahead of print.
19.  Dylla SJ, Beviglia L, Park IK, Chartier C, Raval J, Ngan L, et.al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS ONE 2008; 3:2428.
20.  Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006; 444: 756-760.
21.  Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 2007; 1: 389-402.
22.  Fang DD, Kim YJ, Lee CN, Aggarwal S, McKinnon K, Mesmer D, Norton J, Birse CE, He T, Ruben SM, Moore PA. Expansion of CD133(+) colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery. Br J Cancer 2010; 102: 1265-1275.