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PROJECT For Pharmaceutical Biotechnology 2011-2012

Submitted By
Name: Gopinath Srivastava Programme: M.Sc. 2st term Email: gopinath.srivastava@gmail.com Mob.9999059763 Date of Submission:16/04/2012

Submitted To
Dr. Simendra Singh Department of Biotechnology

Department of Biotechnology School of Engineering and Technology Sharda University, Greater Noida

Research Article 01 SECTION A (1.5)

Title: To Increased Lysis of Stem Cells but Not Their Differentiated Cells by Natural Killer Cells, De-Differentiation or Reprogramming Activates NK Cells. Name of Authors: Han-Ching Tseng, Aida Arasteh, Avina Paranjpe, Antonia Teruel, Wendy Yang, Armin Behel, Jackelyn A. Alva, Gina Walter, Christian Head, Tomo-o Ishikawa, Harvey R. Herschman, Nicholas Cacalano, April D. Pyle, No-Hee Park, Anahid Jewett. Affiliation: Division of Oral Biology and Oral Medicine, School of Dentistry and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California Los Angeles, Los Angeles, California, United States of America. Name of Journal: PLoS ONE. Impact Factor: 4.411. Year in which article published: July 2010 Volume: 5 Page No.: 11590 Issue: 7

SECTION B Objectives :i.

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To this study are to demonstrate the increased lysis of stem cells but not their differentiated counterparts by the NK cells and to determine whether disturbance in cell differentiation is a cause for increased sensitivity to NK cell mediated cytotoxicity. In addition, human embryonic stem cells (hESCs) were also lysed greatly by the NK cells. To study the patients with cancer may benefit from repeated allogeneic NK cell transplantation for specific elimination of cancer stem cells.

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SECTION C Statistical model used for data analysis:-

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An unpaired, two-tailed student t- test was performed for the statistical analysis. One way ANOVA with a Bonferroni post test was used to compare the different groups.

Principle: A t-test is any statistical hypothesis test in which the test statistic follows a Student's t distribution if the null hypothesis is supported. It is most commonly applied when the test statistic would follow anormal distribution if the value of a scaling term in the test statistic were known. When the scaling term is unknown and is replaced by an estimate based on the data, the test statistic (under certain conditions) follows a Student's t distribution. In statistics, analysis of variance (ANOVA) is a collection of statistical models, and their associated procedures, in which the observed variance in a particular variable is partitioned into components attributable to different sources of variation. In its simplest form, ANOVA provides a statistical test of whether or not the means of several groups are all equal, and therefore generalizes t-test to more than two groups.

SECTION D Summary:

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We screened a number of different primary oral squamous cellcarcinomas (OSCC) derived from patients at UCLA, and selected to concentrate on two specific primary tumors based on their phenotypic characteristics and sensitivity to NK cell mediated cytotoxicity. The results also indicated that the levels of NK cell cytotoxicity may vary depending on the expression and function of NFkB in tumors. Thus, increased NFkB appears to be an important factor of differentiation, survival and function of primary oral tumors during their interaction with NK cells. patients with cancer may benefit from repeated allogeneic NK cell transplantation for specific elimination of cancer stem cells. This observation is in agreement with the previously published results demonstrating decreased secretion of VEGF during the progression of head and neck tumo

HYPOTHESIS
UCLA researchers have found that activated NK cells can lyse cancer stem cells, providing a promising approach to the prevention of disease establishment and progression. BACKGROUND: Taken as a whole, roughly half of patients receiving treatment for invasive cancer die. Conventional radiation and chemotherapies have largely failed in improving survival and, since they are non-specific, often result in multiple adverse side effects. Immuno-based cancer treatment offers the possibility of higher specificity, but current therapies are limited in their effectiveness. Immunomodulators, including the EGFR antibody (Erbitux), can eliminate differentiated tumors but are ineffective in removing cancer stem cells and therefore do not fully eradicate the disease. T cell-mediated immunotherapies require an antigen that is both highly expressed and restricted to the tumor, so they are effective in only a small subset of cancers. In contrast to T cells, NK cells do not recognize foreign antigens, but rather detect changes in self-molecules displayed at the surface of autologous cells. NK cells can recognize and kill cancer stem cells, but are often inactivated in cancer patients. Methods to induce the NK-mediated killing of cancer cells, specifically cancer stem cells, could provide new therapies in the treatment of cancer. INNOVATION: The researchers have found that activated NK cells induce the death of patient derived tumors and human stem cells, including Mesenchymal Stem Cells (MSCs) and Osteoblasts. Administration of activated NK cells may be effective in eliminating cancer stem cells to fully eradicate the disease. POTENTIAL APPLICATIONS

Elimination of cancer stem cells by direct delivery of activated NK cells to tumor site. Treatment of metastatic cancer by systemic administration of activated NK cells.

ADVANTAGES:

NK cells have the potential to fully remove the cancer since they target stem cells rather than differentiated tumors. NK cells can be delivered locally to the tumor site, thereby reducing the likelihood of off-target effects. Unlike T cells, NK cells do not require foreign antigens for detection and thus can be utilized for the treatment of various cancer types.

DEVELOPMENT-TO-DATE: The investigators have shown that activated NK cells can lyse patient-derived oral tumors and human embryonic stem cells in vitro.