Posts Tagged ‘rehabilitation’

Preclinical development of tumor therapeutic agent begins

amcure, one of the partners of which is KIT, now plans to use the funds acquired for the further development of candidate agents identified by the team of Dr. Veronique Orian-Rousseau, KIT, for the treatment of metastatic tumors. The candidate substances bind specifically to a certain so-called isoform of the surface molecule CD44 and, thus, specifically interfere with central signal paths of tumor growth, while other types of cells remain unaffected. New formation of blood vessels supplying the tumor (angiogenesis) and migration of cancer cells and their invasion into other organs (development of metastases) are inhibited. “Data from animal tests reveal that our molecules do not only stop the growth of primary tumors, but may also prevent metastasis development and cause the regression of existing metastases,” says Dr. Alexandra Matzke, Chief Scientific Officer of amcure. The clinical studies that are to start in the next years will show whether these positive effects will also occur in human patients without any side effects.

The target molecule of amcure’s development candidates, CD44v6, plays a significant role for many types of tumors. It was discovered in the 1990s by Professor Helmut Ponta and his team at KIT. CD44 and its isoforms are increasingly considered significant factors for the spreading and formation of metastases. Blocking the receptor CD44v6 might open up opportunities for a wide-ranging application in tumor therapy.

“If these observations will be confirmed by clinical trials with patients, amcure can lay the foundation for treating tumors much more effectively and with far fewer side effects,” emphasizes Dr. Harald Poth, Senior Investment Manager of LBBW Venture Capital.

The next development steps will be funded by a consortium headed by LBBW Venture Capital, with participations from KfW, MBG Mittelst√§ndische Beteiligungsgesellschaft Baden-W√ľrttemberg, S-Kap Beteiligungen Pforzheim, BioM AG as well as private investors. In addition, the company receives funding by the Federal Ministry of Education and Research (BMBF) under the special program Spinnovator managed by Ascenion GmbH. The funds are so-called series A funds provided by venture capital investors to support growth of the young KIT spinoff in the next years. Prior to and during the establishment of the company, amcure was financed by its partner KIT and the Helmholtz Association as well as from federal funds.

“The consortium around LBBW Venture consists of experienced investors having extensive networks. We are happy to have convinced them of our development approach so that now the next steps in the preclinical and clinical stages can be financed,” says Dr. Matthias Klaften, Chief Executive Officer of amcure.

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Statistical Approach for Calculating Environmental Influences in Genome-Wide Association Study (GWAS) Results

The approach fills a gap in current analyses. Complex diseases like cancer usually arise from complex interactions among genetic and environmental factors. When many such combinations are studied, identifying the relevant interactions versus those that reflect chance combinations among affected individuals becomes difficult. In this study, the investigators developed a novel approach for evaluating the relevance of interactions using a Bayesian hierarchal mixture framework. The approach is applicable for the study of interactions among genes or between genetic and environmental factors.

Chris Amos, PhD, senior author of the paper said, “These findings can be used to develop models that include only those interactions that are relevant to disease causation, allowing the researcher to remove false positive findings that plague modern research when many dozens of factors and their interactions are suggested to play a role in causing complex diseases.”

The model evaluates “gene by gene” and “gene by environment” factors by looking at specific DNA sequencing variations. Complex diseases are caused by multiple factors. In some cases a genetic predisposition or abnormality may be a factor. A person’s healthy lifestyle and environment, however, may help him or her overcome a genetic vulnerability and avoid a chronic disease like cancer. In other situations, a person whose DNA does not have an abnormality may develop one when exposed to known carcinogens like tobacco smoke or sunburn.

“Understanding the combinations of genetic and environmental factors that cause complex diseases is important,” said Amos, associate director of population sciences and deputy director of Norris Cotton Cancer Center, “because understanding the genetic architecture underlying complex disease may help us to identify specific targets for prevention or therapy upon which interventions may appropriately reduce the risk of cancer development or progression.”

The study applied the model in cutaneous melanoma and lung cancer genetic sequences using previously identified abnormalities (known as single nucleotide polymorphisms or SNPs) with environmental factors introduced as independent variables. The Bayesian mixture model was compared with the traditional logistic regression model. The hierarchal model successfully controlled the probability of false positive discovery and identified significant interactions. It also showed good performance on parameter estimation and variable selection. The model cannot be applied to a complete GWAS because if its reliance on other probability models (MCMC ). It is most effective when applied to a group of SNPs.

“The method was effective for the study of melanoma and lung cancer risk because these cancers develop from a complex interaction between genetic and environmental factors but understanding how these factors interact has been difficult to achieve without the sophisticated modeling that has been developed in this study,” said Amos.

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Surgery associated with better survival for patients with advanced laryngeal cancer

Approximately 11,000 to 13,000 cases of laryngeal cancer are diagnosed each year and squamous cell carcinoma accounts for the vast majority of these tumors. Prior to 1991, total surgical removal of the larynx with postoperative radiation was the standard of care for advanced cancer. Since then, chemoradiation has become increasingly popular treatment because it can preserve the larynx.

The authors evaluated survival outcomes for surgical vs. nonsurgical treatment for advanced laryngeal cancer. The authors used data from the Surveillance, Epidemiology and End Results (SEER) database for their study of 5,394 patients diagnosed with stage III or IV laryngeal squamous cell carcinoma between 1992 and 2009.

Patients who had surgery had better 2-year and 5-year disease-specific survival (70 percent vs. 64 percent and 55 percent vs. 51 percent, respectively) and 2-year and 5-year overall survival (64 percent vs. 57 percent and 44 percent vs. 39 percent, respectively) than patients who did not under surgery. The use of nonsurgical treatment increased over time: 32 percent in the 1992 to 1997 patient group, 45 percent in the 1998 to 2003 group and 62 percent in the 2004 to 2009 group. The gap in survival between the two groups consistently narrowed over subsequent years. Patients who were diagnosed between 2004 and 2009 had better survival than those diagnosed earlier and this may be due to improvements in radiation and chemotherapy strategies.

“Patients need to be made aware of the modest but significant survival disadvantage associated with nonsurgical therapy as part of the shared decision-making process during treatment selection,” researchers noted.

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