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Sexta-feira, 03.10.14

Cell Line Research to Produce Vaccine Against Head, Neck and Cervical Cancers

Baylor IIR, Antitope Begin Collaboration in Cell Line Research to Produce Vaccine Against Head, Neck and Cervical Cancers

Posted by: Chris Comish June 9, 2014

Baylor Institute for Immunology Research (BIIR), a major research center for the study of translational immunology, has announced that it will feature a new manufacturing cell line developed by Antitope Ltd., an Abezna company, which will utilize Antitope’s Composite CHO technology. Antitope’s cell line will help produce BIIR’s newly developed vaccine for dendritic cells, which will be used in the treatment of both head and neck as well as cervical cancers. BIIR is currently developing a variety of vaccines targeting the treatment of cancer and other diseases as well.

Antitope’s Composite CHO technology was developed for generating stable cell lines for the production of high yields of proteins and antibodies that can be readily used in the cGMP manufacturing process. This project is yet another important milestone between Antitope and BIIR, whom partnered several years ago. Their first project together was applying Antitope’s Composite Human Antibody technology to humanize a number of BIIR antibodies. These antibodies have gone on to become an important tool in the development of BIIR’s therapeutic vaccines.

Matthew Baker, CSO of the Abezna group and co-founder of Antitope, said that the company was “delighted to be working with BIIR again and to have the opportunity to help advance one of its novel therapeutic dendritic-cell-targeting vaccines towards the clinic.”

Gerard Zurawski, co-director of BIIR and Director of the Center for Biotechnology at BIIR, also commented that “we are thrilled to be continuing our working relationship with Matthew Baker and his team at Antitope on this program and we anticipate that the vaccine can now be rapidly advanced to clinical studies.”

Dr. Michael Ramsay, president of Baylor Research Institute, added: “As part of the Baylor Scott & White Health system, BIIR can leverage the GMP manufacturing capability of facilities in Temple, Texas-established with funding from Cancer Prevention Research Institute of Texas (CPRIT)– and our system-wide clinical trials infrastructure, to develop products for cancer patients across the globe.”


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por cyto às 12:59

Sexta-feira, 03.10.14

Proteins mark metastasizing breast cancer cells

Delicia Honen Yard

April 29, 2013

Proteins mark metastasizing breast cancer cells

Researchers have identified a novel signature of circulating tumor cells (CTCs) from breast cancer that metastasize to the brain and that may not be detected by the method of identification cleared by the FDA.

The FDA-approved CellSearch platform is based on the detection of antibodies that target the epithelial cell adhesion molecule (EpCAM), according to a statement from Baylor College of Medicine in Houston, Texas. But the biomarkers identified by Dario Marchetti, who is a pathologist at Baylor, and colleagues are present in CTCs that are EpCAM-negative, and as such, would not be detected by CellSearch.

The four brain metastasis selected markers (BMSMs) identified by Marchetti's team are human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), heparanase (HPSE), and Notch1. These four proteins were already known to be associated with cancer metastasis. Now, this pattern of proteins has been found to spell out the signature of CTCs that metastasize to the brain.

“CTC lines expressing the BMSM signature were highly invasive and capable of generating brain and lung metastases when xenografted [in mice],” affirmed Marchetti's group in Science Translational Medicine (2013;5[180]:180ra48). “The presence of proteins of the BMSM CTC signature was also detected in the metastatic lesions of animals.”

Identifying and understanding the characteristics of CTCs are initial steps in developing new treatments for metastatic disease. Marchetti noted in the Baylor statement that he and his fellow investigators are not claiming that these biomarkers are the only important ones; the investigators are continuing to search for novel markers in brain metastasis that will make diagnosis and monitoring even more targeted.

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por cyto às 12:45

Sexta-feira, 03.10.14

Circulating Tumor Cells Prognostic in Early Breast Cancer

Circulating Tumor Cells Prognostic in Early Breast Cancer

(HealthDay News) -- Circulating tumor cells (CTCs) are prognostic of poor survival in early breast cancer, according to a study published online May 15 in the Journal of the National Cancer Institute.

Brigitte Rack, M.D., from the Ludwig-Maximilians-University Munich in Germany, and colleagues used the CellSearch System to analyze CTCs in 2,026 patients with early breast cancer before adjuvant chemotherapy and in 1,492 patients after chemotherapy. Nucleated cells expressing cytokeratin and lacking CD45 were classified as CTCs. The median follow-up was 35 months.

The researchers found that 21.5 percent of patients had CTCs before chemotherapy, including 19.6 percent of node-negative and 22.4 percent of node-positive patients (P < 0.001). There was no correlation with tumor size, grading, or hormone receptor status. CTCs were detected in 22.1 percent of patients after chemotherapy. CTC presence correlated with poor disease-free survival (DFS), distant DFS, breast cancer-specific survival, and overall survival (OS). In multivariate analysis, CTCs were confirmed as independent prognostic markers for DFS (hazard ratio, 2.11; P < 0.0001) and OS (hazard ratio, 2.18; P = 0.002). Patients with at least five CTCs per 30 mL blood had the worst prognosis for DFS and OS (hazard ratios, 4.51 and 3.60, respectively). After chemotherapy, the presence of CTCs had a negative impact on DFS and OS (hazard ratios, 1.12 [P = 0.02] and 1.16 [P = 0.06], respectively).

"These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer," the authors write.

Several authors disclosed financial ties to the pharmaceutical companies that funded the translational research part of the SUCCESS trial.

May 20, 2014


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por cyto às 12:39

Sexta-feira, 03.10.14

Cancer Cells Adapt Energy Needs to Metastasize to Other Organs

MD Anderson Study Finds Cancer Cells Adapt Energy Needs to Metastasize to Other Organs

Posted by: Charles Moore September 22, 2014

Houston’s University of Texas MD Anderson Cancer Center says that if you want to understand why cancer cells metastasize — think of Sparta, the Greek city-state that as a political and military power spanned the cusp of the bronze and early iron ages from about 650 BC to the Roman conquest in 146 BC. Spartan warriors were fed a special diet that better prepared them for the demands of battle on distant fields.

MD Anderson scientists say cancer cells that metastasize may do the same thing, according to a new study that has revealed previously unknown differences in cancer cells that continue to grow at the original tumor site, and those that travel to invade other organs. Given that a cancer cells’ relentless ability to metastasize is the primary cause of cancer-related death, understanding how they successfully migrate could be lifesaving.

Researchers at MD Anderson and affiliated institutions in the U.S., Germany, and Brazil have found that cancer cells traveling to other sites have different energy needs compared with their stay-at-home siblings which continue to proliferate at the original tumor site. The study results are published in the Sept. 21 online edition of the journal Nature Cell Biology.

The scientists suggest that the reason may lie with the protein, PGC-1, a type of transcription co-activator crucial to regulation of cellular metabolism. They say PGC-1 appears to play a role in how cancer cells are able to acquire unique energy sources that allow them to travel and spread cancer in the body.

The research article, entitled “PGC-1 mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis” (Published online 21 September 2014 Nature Cell Biology doi:10.1038/ncb3039), is coauthored by Valerie S. LeBleu and Raghu Kalluri of the Department of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, also affiliated with Joyce T. O’Connell at the Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center in Boston, Massachusetts; Karina N. Gonzalez Herrera and Marcia C. Haigis of the Department of Cell Biology, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, Massachusetts; Harriet Wikman and Klaus Pantel of the Department of Tumor Biology, University Medical Center Hamburg-Eppendorf in Hamburg, Germany; Fernanda Machado de Carvalho, Aline Damascena, Ludmilla Thome Domingos Chinen and Rafael M. Rocha of the International Research Center, A. C. Camargo Cancer Center at Sao Paulo, Brazil; and John M. Asara of the Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Harvard Medical School Department of Medicine at Boston, Massachusetts.

The coauthors note that cancer cells can divert metabolites into anabolic pathways to support their rapid proliferation and to accumulate cellular building blocks required for tumor growth. However, they say the specific bioenergetic profile of invasive and metastatic cancer cells is unknown.

In their paper, the researchers report that migratory/invasive cancer cells specifically favor mitochondrial respiration and increased ATP production, and that invasive cancer cells use the transcription coactivator peroxisome proliferator-activated receptor gamma, coactivator 1 alpha ( PPARGC1A, also known as PGC-1) to enhance oxidative phosphorylation, mitochondrial biogenesis and the oxygen consumption rate.

The coauthors report that clinical analysis of human invasive breast cancers revealed a strong correlation between PGC-1 expression in invasive cancer cells and formation of distant metastases. They observe that silencing of PGC-1 in cancer cells suspended their invasive potential and attenuated metastasis without affecting proliferation, primary tumour growth or the epithelial-to-mesenchymal program. Inherent genetics of cancer cells can determine the transcriptome framework associated with invasion and metastasis, and mitochondrial biogenesis and respiration induced by PGC-1 are also essential for functional motility of cancer cells and metastasis.

“New therapy strategies are beginning to focus on the unique vulnerabilities of cancer cell metabolism. Determining the metabolic requirements of invasive cancer cells could be of therapeutic value,” says Valerie LeBleu, Ph.D. , an assistant professor of cancer biology at MD Anderson and lead author of the Nature Cell Biology paper in a MD Anderson release. “We found that invading cancer cells rely on mitochondria during their transition to other cancer sites.”

Dr. LeBleu’s research program bridges cancer biology with organ fibrosis, with an emphasis in understanding the underlying molecular mechanisms regulating the pathological remodeling of the affected organ. Her research efforts focus on elucidating the functional contribution of pathological stroma in cancer initiation, solid tumor growth, and metastatic dissemination. Her lab makes extensive use of and continues to develop novel genetically engineered mouse models of lung and breast cancer as well as organ fibrosis including lung and kidney fibrosis. Ongoing projects include the study of lung neoplasia and metastatic growth and study of the metabolic cooperation of stroma and cancer cells in breast and lung cancer progression.

Cancer cells use PGC-1 to stimulate the growth of new mitochondria, the cell s power plants that generate ATP, an energy currency used by cells to grow. Metastasizing cells also rely on PGC-1 for a process known as oxidative phosphorylation that boosts ATP during the cell s journey to other sites. If mitochondria is the kitchen, then PGC-1 is the chef, ATP the entre and oxidative phosphorylation a key ingredient. This overall process, mitochondria respiration, allows some cancer cells to harness the required energy to survive the hostile journey through tumor and normal issue, blood vessels, and entry into new organs.

In other words, returning to the Spartan analogy, some cancer cells are programmed to eat at home, while others have a special diet that allows them to travel to other sites. If there was a therapeutic way to stop the migrating cells from packing a lunch ahead of time, it could potentially halt their journey, and the MD Anderson scientists say suppressing PGC-1 appears to accomplish this.

“The most dangerous cancer cells are the ones that can efficiently move and find a new home, says Raghu Kalluri, M.D., Ph.D., chair of cancer biology and an investigator on the study, which as noted above revealed a strong correlation between PGC-1 expression in invasive cancer cells and the formation of distant metastases in breast cancer patients.

The study was funded by the Cancer Prevention and Research Institute of Texas, MD Anderson Cancer Center, the Department of Defense Cancer Research Predoctoral Traineeship Award (W81XWH-09-1-0008). Dr. Kalluri is also funded by the National Institutes of Health (CA 125550, CA 1555370, CA 151925, DK081576, DK055001, CA12096405, and CA00651646).

Sources:University of Texas, MD Anderson Cancer Center Nature Cell Biology Wikipedia

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por cyto às 12:28

Sexta-feira, 03.10.14

Gastrointestinal Cancers


Gastrointestinal Cancers Studied Using Caris Life Science’s Technology,

Presented at ASCO Meeting

Posted by: Maureen Newman June 4, 2014

At the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), Caris Life Sciences revealed more positive results from studies using their Caris Molecular Intelligence™ technology. During the meeting, Fadi Braiteh, MD, from Comprehensive Cancer Centers of Nevada and US Oncology Research, presented a poster detailing the molecular profiles of various types of gastrointestinal cancer and potential drug options for patients.

Earlier in the year, Caris presented data at the 2014 Gastrointestinal Cancers Symposium, and this current work adds to the repertoire of using Caris Molecular Intelligence for gastrointestinal cancers. Clinical data from nine total studies were presented. Notably, the studies included more than 14,000 cases of of 17 different types of gastrointestinal cancer, as well as a subset of nearly 7,000 colorectal cancer patients, all with the intention of opening new treatment options to patients.

“This study, with its large, diverse patient population, including a very large number of patients from the community setting, demonstrates how molecular profiling can be utilized beyond just the university centers, and offers a potential new way to classify gastrointestinal cancers based on the underlying molecular aberrations instead of by organ and tissue of origin,” said Dr. Braiteh in a news release from Caris, regarding the study of 14,207 patients. Up to 70 molecular abnormalities were found in tumor samples. Highlights of the findings include Her2 overexpression, KRAS mutations, PTEN loss of expression, and cMET overexpression in combinations unique to certain subsets of cancers.

“Our analysis showed that cancers from different gastrointestinal subtypes may share the same molecular pathway, suggesting that the same types of targeted therapy may be appropriate across gastrointestinal cancer subtypes, while other types of therapies – whether standard of care or investigational – may be better suited for cancers with more distinct molecular profiles,” concluded Dr. Braiteh.

The other study of 6,892 tumor samples was conducted in conjunction with Penn State Hershey Cancer Institute and was presented by Wafik El-Deiry, MD, PhD and FACP. Highlights from the seven different metastatic tumor sites include Her2 overexpression, Top2A amplification, KRAS mutations, and TOPO1 overexpression in certain metastases that both suggest and eliminate treatment options for patients.

“Whereas KRAS and BRAF mutations can make colorectal cancer especially aggressive, patients with these mutations have long been thought to have limited treatment options, and there are no detailed treatment guidelines that specifically address various sites of metastasis,” explained Dr. El-Deiry. “We identified significant differences among tumors with these mutations, as well as at the different sites of metastasis, providing support for selecting treatments that, in many cases, have not traditionally been considered for patients with colorectal cancer.”

Driving home the power of Caris Molecular Intelligence, Sandeep Reddy, MD, Chief Medical Officer at Caris stated, “Our comprehensive, multiplatform approach to molecular profiling is helping oncologists individualize treatment regimens according to the molecular signature of a patient’s tumor. This year’s ASCO presentations by Caris include posters demonstrating how biomarker analysis can inform treatment guidelines and therapeutic decision-making for patients with various types of gastrointestinal cancer, including those of the colon and rectum, stomach, esophagus, bile duct and gallbladder. Given the substantial breadth and depth of these gastrointestinal studies, we believe these findings should stimulate serious discussion and wider adoption of molecular profiling techniques by the broader oncology community.”

Seventeen percent of all new cancer cases in the United States are malignancies of the digestive system, and these account for more than 25% of cancer-related deaths.

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por cyto às 12:26

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