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Doug Melton's laboratory is interested in the genes and stem cells that give rise to the pancreas and insulin-producing beta cells, with possible therapeutic implications for diabetes. Type 1 or juvenile diabetes is a genetically complex disease caused by an autoimmune destruction of insulin-producing beta (?) cells. We analyze the genes and cells that form the pancreas and use that information to direct differentiation of multipotent stem cells toward the ?-cell fate.
We are extending our work now, with collaborators, to explore ways to protect stem cell-derived beta cells from immune destruction folllowing transplantation.
We use a wide variety of techniques, including functional genomics, chemical screening, tissue explants and grafting for analyzing inductive signals, and developmental genetics for direct assays of gene function.
Should we be successful in directing the differentiation of human cells into functional ? cells, or find signals that cause ? cell replication and regeneration in vivo, we will extend our findings to clinical applications for the treatment of diabetes. Some of these projects were also supported by grants from the National Institutes of Health, the Beta Cell Biology Consortium, the Juvenile Diabetes Research Foundation, and the Harvard Stem Cell Institute. Free resources for science teachers and students, including animations, short films, and apps.
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The term "cancer" describes a group of diseases that are characterized by uncontrolled cellular growth, cellular invasion into adjacent tissues, and the potential to metastasize if not treated at a sufficiently early stage. The CSC hypothesis suggests that the malignancies associated with cancer originate from a small population of stem-like, tumor-initiating cells. The identification of leukemia-inducing cells has fostered an intense effort to isolate and characterize CSCs in solid tumors. Given the similarities between tumor-initiating cells and stem cells, researchers have sought to determine whether CSCs arise from stem cells, progenitor cells, or differentiated cells present in adult tissue. Several characteristics of the leukemia-initiating cells support the stem-cell origin hypothesis.
The differentiation pathway from a stem cell to a differentiated cell usually involves one or more intermediate cell types.
Some researchers have suggested that cancer cells could arise from mature, differentiated cells that somehow de-differentiate to become more stem celllike. Some researchers have proposed that these unique cells may be CSCs.9,30,32,33,38 In this hypothesis, metastatic inefficiency may reflect the relative rarity of CSCs combined with the varying compatibilities of these cells with destination microenvironments. As noted previously, most contemporary cancer treatments have limited selectivity — systemic therapies and surgeries remove or damage normal tissue in addition to tumor tissue. The CSC hypothesis accounts for observed patterns of cancer recurrence and metastasis following an apparently successful therapeutic intervention. These discoveries have led researchers to propose several avenues for treating cancer by targeting molecules involved in CSC renewal and proliferation pathways. Adipose stem cell therapy as an alternative treatment to help manage the complications of Diabetes. Adult Stem Cells are obtained from ITC Bank from donor tissue or Autologous Transplant is harvested from the patient own Adipose Tissue and it takes 21 days to culture, differentiate and administered the Adult Stem Cells to the patient. Therefore, our medical staff will be contacting you after 1 month, 3 months, 4 months, and 1 year to follow up on your condition. IntroductionType I Diabetes is an autoimmune disorder in which the pancreas produces little or no insulin. Idiopathic type I diabetes: This is the rarest form of Type I Diabetes with no known cause.
What Are the Symptoms of Diabetes Type I?Increased thirst and frequent urination, extreme hunger, weight loss, blurred vision and fatigue are some of the symptoms of type I diabetes. Random Blood sugar test: whereby a blood sample is taken at random, regardless of when you last ate. Once you are diagnosed with diabetes, physician may ask you to undergo other tests to distinguish between type I and type II diabetes. Treatments for type I diabetes is determined by your physician based on various factors like your age, overall health, medical history, extent of the disease, and your tolerance to medications and procedures or therapies. Insulin and other medications: People with severe type I diabetes needs insulin to survive.
Transplantations: Researches have led to improved methods of managing and curing type I diabetes. Here are few simple, effective diabetes self-care tips that can reduce diabetes breakouts and control future breakouts. We do not claim any affiliation with or to in any way connected to any manufacturer of offered products nor do we claim to be affiliated with or in any way connected to any holders of trademarks. Thus, the challenge finding new treatments or a cure can be divided into two problems: blocking or reversing the autoimmune attack and providing new ? cells. Genetic marking in mice has allowed us to map the lineage of progenitor cells that give rise to the exocrine, endocrine, and ductal components of the pancreas.
Surgery, radiation therapy, and systemic treatments such as chemotherapy or hormonal therapy represent traditional approaches designed to remove or kill rapidly-dividing cancer cells.
Tumors originate from the transformation of normal cells through the accumulation of genetic modifications, but it has not been established unequivocally that stem cells are the origin of all CSCs. Although cancer researchers first isolated CSCs in 1994,14 the concept dates to the mid-19th century. Stem cell-like populations have since been characterized using cell-surface protein markers in tumors of the breast,17 colon,18 brain,19 pancreas,20,21 and prostate.22,23 However, identifying markers that unequivocally characterize a population of CSCs remains challenging, even when there is evidence that putative CSCs exist in a given solid tumor type. Stem cells are distinguished from other cells by two characteristics: (1) they can divide to produce copies of themselves, or self-renew, under appropriate conditions and (2) they are pluripotent, or able to differentiate into most, if not all, mature cell types. Recently, the CSCs associated with AML have been shown to comprise distinct, hierarchically-arranged classes (similar to those observed with hematopoietic stem cells) that dictate distinct fates.31 To investigate whether these CSCs derive from hematopoietic stem cells, researchers have used a technique known as serial dilution to determine the CSCs' ability to self-renew.
These intermediate cells, which are more abundant in adult tissue than are stem cells, are called progenitor or precursor cells. In this scenario, the requisite oncogenic (cancer causing) genetic mutations would need to drive the de-differentiation process as well as the subsequent self-renewal of the proliferating cells.
These methods must therefore be employed judiciously to limit adverse effects associated with treatment.


In clinical practice, however, some cancers prove quite aggressive, resisting chemotherapy or radiation even when administered at relatively early stages of tumor progression.
In the face of radiation, the CSCs appear to survive preferentially, repair their damaged DNA more efficiently, and begin the process of self-renewal.
Potential strategies include interfering with molecular pathways that increase drug resistance, targeting proteins that may sensitize CSCs to radiation, or restraining the CSCs' self-renewal capacity by modifying their cell differentiation capabilities.9 In each case, successful development of a therapy would require additional basic and clinical research.
Governed by an intricate, complex interplay of molecular signals, cancers often resist systemic treatments. Cancer stem cell science is an emerging field that will ultimately impact researchers' understanding of cancer processes and may identify new therapeutic strategies. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. Targeted therapy for the treatment of advanced non-small cell lung cancer: a review of the epidermal growth factor receptor antagonists. Cancer Stem Cells—Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells. Human myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Stem-cell abundant proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells.
Tumor dormancy and cancer stem cells: implications for the biology and treatment of breast cancer metastasis. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells.
The stem cells may have the potential to replace countless cells of the body, insulin producing cells included. Insulin is a hormone that is needed to convert sugar (glucose), starches and other food into energy needed for daily life. This is an autoimmune disorder in which the body’s immune system destroys or attempts to destroy, the cells in the pancreas that produce insulin. Women might have frequent vaginal infection and yeast infection while men face yeast infection alone. Some of them include pancreas transplantation, islet transplantation and stem cell transplantation. We have focused on the latter, pursuing three complementary approaches aimed at making new ? cells for diabetics. In parallel, using biological and chemical screens, we investigate the regulatory genes that specify pancreatic cell fates. For example, in 2000, the relative survival rate five years following diagnosis of melanoma (skin cancer) was greater than 90%; that of cancers of the brain and nervous system was 35%. Tumors and other structures that result from aberrant cell growth, contain heterogeneous cell populations with diverse biological characteristics and potentials.
The CSC hypothesis therefore does not imply that cancer is always caused by stem cells or that the potential application of stem cells to treat conditions such as heart disease or diabetes, as discussed in other chapters of this report, will result in tumor formation. The issue is currently under debate,9,12 and this section will review several theories about the cellular precursors of cancer cells (see Fig.
The molecular pathways that maintain "stem-ness" in stem cells are also active in numerous cancers.
If CSCs arise from normal stem cells present in the adult tissue, de-differentiation would not be necessary for tumor formation. Serial dilution involves transplanting cells (usually hematopoietic stem cells, but in this case, CSCs) into a mouse during a bone-marrow transplant.
They are partly differentiated cells present in fetal and adult tissues that usually divide to produce mature cells.
This model leaves open the possibility that a relatively large population of cells in the tissue could have tumorigenic potential; a small subset of these would actually initiate the tumor. Moreover, these approaches are often only temporarily effective; cancers that appear to be successfully eliminated immediately following treatment may recur at a later time and often do so at a new site. These tumors therefore have an increased likelihood of metastasizing, confounding further treatment strategies while compromising the cancer patient's quality of life. Researchers must characterize the CSCs associated with a given tumor type, identify relevant molecules to target, develop effective agents, and test the agents in pre-clinical models, such as animals or cell lines. Yet the uncontrolled cellular growth that characterizes cancers may paradoxically hold the key to understanding the spread of disease. However, much remains to be learned about these unique cells, which as of yet have not been identified in all tumor types. The undifferentiated cells may heal the body by replacing ones plagued with disease by regenerating new cells. Regular follow-up also helps us evaluate the effectiveness of our clinical protocols and improve them based on observed outcomes. Although Type I Diabetes can develop at any age, it typically appears during childhood or adolescence and hence called as juvenile diabetes. Poor diet (malnutrition), genetic, and exposure to certain virus in the environment may also trigger the condition. Dry mouth, slow healing of sores or cuts, itching skin, especially in the groin or vaginal area are some of the symptoms of type I diabetes. Appropriate diet, exercise, and careful self-monitoring of blood sugar levels at equal intervals as directed by your physician becomes major part of the treatment for type I diabetes. Oral insulin might interfere with the stomach enzymes and is not prescribed to lower blood sugar levels.


These studies have identified a set of transcription factors and intercellular signaling molecules (growth factors) that are responsible for the stepwise differentiation of normal pancreatic development.
Once a cancer has metastasized (or spread to secondary sites via the blood or lymph system), however, the survival rate usually declines dramatically.
As such, a researcher sequencing all of the genes from tumor specimens of two individuals diagnosed with the same type of lung cancer will identify some consistencies along with many differences. For example, cancer surgeons may be unable to remove all of the tumor tissue due to its location or extent of spreading. For instance, the proteins Nanog, nucleostemin, and musashi1, which are highly expressed in embryonic stem cells and are critical to maintaining those cells' pluripotency, are also highly expressed in malignant cervical epithelial cells.27 While this finding does not indicate the existence of cervical cancer CSCs, it suggests that these proteins may play roles in cervical carcinogenesis and progression. This similarity has led scientists to propose that cancers may arise when some event produces a mutation in a stem cell, robbing it of the ability to regulate cell division. In this scenario, cancer cells could simply utilize the existing stem-cell regulatory pathways to promote their self-renewal. Prior to the transplant, this "primary recipient" mouse's natural supply of hematopoietic stem cells is ablated. Agents that target molecules implicated in cancer pathways have illustrated the power of a selective approach, and many researchers and drug developers are shifting toward this paradigm.
However, by targeting fundamental CSC cellular signaling processes, it is possible that a given treatment could be effective against multiple tumor types.
It has long been postulated that tumors form and proliferate from the actions of a small population of unique cells.
At present, evidence continues to mount to support a CSC Hypothesis—that cancers are perpetuated by a small population of tumor-initiating cells that exhibit numerous stem cell-like properties. Type I Diabetes is known by a variety of names like insulin-dependent diabetes mellitus (IDDM), brittle diabetes, and sugar diabetes. Another cause could be the secretion of some hormones in blood which act as antagonists to insulin. Seek medical attention if you feel nauseated, week, have fainting spells or breathing more deeply and rapidly than normal.
Regular monitoring of the hemoglobin A1C levels will also help you keep your blood sugars within range.
Insulin comes in several forms that include rapid-acting insulin, long-acting insulin and intermediate options. This genetic and cellular knowledge of pancreatic developmental biology guides our approach to the directed differentiation of stem cells.
In fact, cancerous tissues are sufficiently heterogeneous that the researcher will likely identify differences in the genetic profiles between several tissue samples from the same specimen. Radiation and chemotherapy, on the other hand, are non-specific strategies—while targeting rapidly-dividing cells, these treatments often destroy healthy tissue as well.
Subsequent analysis of populations of leukemia-initiating cells from various AML subtypes indicated that the cells were relatively immature in terms of differentiation.16 In other words, the cells were "stem-like"—more closely related to primitive blood-forming (hematopoietic) stem cells than to more mature, committed blood cells. This figure illustrates 3 hypotheses of how a cancer stem cell may arise: (1) A stem cell undergoes a mutation, (2) A progenitor cell undergoes two or more mutations, or (3) A fully differentiated cell undergoes several mutations that drive it back to a stem-like state. The ability to self-renew gives stem cells long lifespans relative to those of mature, differentiated cells.30 It has therefore been hypothesized that the limited lifespan of a mature cell makes it less likely to live long enough to undergo the multiple mutations necessary for tumor formation and metastasis.
If the transplant is successful and if the cells undergo substantial self-renewal, the primary recipient can then become a successful donor for a subsequent, or serial, transplant. However, if a tissue contains a sufficient population of differentiated cells, the laws of probability indicate that a small portion of them could, in principle, undergo the sequence of events necessary for de-differentiation. If the CSC hypothesis proves to be correct, then a strategy designed to target CSCs selectively could potentially stop the "seeds" of the tumor before they have a chance to germinate and spread. The observation that metastatic cancer cells exhibit experimental and clinical behaviors highly reminiscent of the classical properties of stem cells has led researchers to search for and to characterize "cancer stem cells" believed to be implicated in the cancer process.
Whether or not the Hypothesis ultimately proves true in all cases, understanding the similarities between cancer cells and stem cells will illuminate many molecular pathways that are triggered in carcinogenesis. Examples include regular insulin (Humulin R, Novolin R, others), insulin isophane (Humulin N, Novolin N), insulin lispro (Humalog), insulin aspart (NovoLog) and insulin glargine (Lantus). Researchers are experimenting with islet cell transplants, which provide new insulin producing cells from a donor pancreas. Using both embryonic and induced pluripotent stem cells (ES and iPS, respectively, from mice and humans), we aim to create functional ? cells, using a stepwise differentiation protocol wherein specific signals are used to tell the cells which fate to adopt. While some groupings of genes allow scientists to classify organ-or tissue-specific cancers into subcategories that may ultimately inform treatment and provide predictive information, the remarkable complexity of cancer biology continues to confound treatment efforts. Recently, several agents that target specific proteins implicated in cancer-associated molecular pathways have been developed for clinical use.
In all 3 scenarios, the resultant cancer stem cell has lost the ability to regulate its own cell division. Following cell division within primary recipients, a subset of the AML-associated CSCs divided only rarely and underwent self-renewal instead of committing to a lineage. In general, it is said that the body’s immune system which fights against virus and bacteria, attacks and destroys insulin producing cells in the pancreas. You require medical attention in such cases, which indicates the presence of ketoacidosis, a potentially deadly complication of type I diabetes. Depending on your needs, your doctor may prescribe a mixture of insulin types to use throughout the day and night. Stem cell transplantation is little risky since it involves shutting down of the immune system and building it up again. These include trastuzumab, a monoclonal antibody that targets the protein HER2 in breast cancer,5 gefitinib and erlotnib, which target epidermal growth factor receptor (EGFR) in lung cancer,6 imatinib, which targets the BCR-ABL tyrosine kinase in chronic myelogenous leukemia,7 the monoclonal antibodies bevacizumab, which targets vascular endothelial growth factor in colorectal and lung cancer,8 and cetuximab and panitumumab, which target EGFR in colorectal cancer.8 These agents have shown that a targeted approach can be successful, although they are effective only in patients who feature select subclasses of these respective cancers.
However, the characterization of CSCs will likely play a role in the development of novel targeted therapies designed to eradicate the most dangerous tumor cells, that may be resistant to current chemotherapy regimens, thereby providing researchers and clinicians with additional targets to alleviate the burden of cancer. This means that your blood sugar is higher than normal but not high enough to be called diabetes.



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Comments

  1. NASTYA

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    02.08.2014

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    02.08.2014