Transforming Growth Factor Beta Type Ii Receptor Mutants In Human Cancer

Transforming Growth Factor- ß in Cancer Therapy, Vols. 1 and 2, provides a compendium of findings about the role of transforming growth factor- ß (TGF- ß) in cancer treatment and therapy. The second volume, Cancer Treatment in Therapy, is divided into three parts. The companion volume details the role of TGF- ß on basic and clinical biology.

Transforming Growth Factor- ß in Cancer Therapy, Vols. 1 and 2, provides a compendium of findings about the role of transforming growth factor- ß (TGF- ß) in cancer treatment and therapy. The first volume, Basic and Clinical Biology, is divided into three parts. This volume’s companion, Cancer Treatment in Therapy, examines transforming growth factor- ß in other developing and advanced cancers and methods of treatment and therapy.

Transforming Growth Factor-Beta (TGF-Beta) is the most potent known inhibitor of cell cycle progression of normal mammary epithelial cells. In general, advanced breast cancers are refractory to TGF-Beta-mediated growth inhibition. The TGF-Beta type I and type II receptors (T-Beta-R-I and -II) are the primary transducers of TGF-Beta's antiproliferative effects. It is our working hypothesis that TGF-Beta-resistance is caused by lesions in the T-Beta-R genes. Using touch preps of primary breast carcinomas, we showed that approximately 50% of primary breast carcinomas contain subpopulations of cells that have lost one or both copies of the T-Beta-R-I or -II gene. Screening of the T-Beta-R-I and -II genes for the presence of mutations using PCR-SSCP and DNA sequencing indicate that a particular missense mutation (S387Y) in T-Beta-R-I is present in approximately 6% of primary cancers and 42% of axillary lymph node metastases. Finally, we have generated antibodies that specifically recognize the activated (phosphorylated) forms of Smad2 and -3. These allow us to assess in situ whether breast cancer cells are responding to TGF-Beta, and whether T-Beta-R defects are present or not. Approximately 12% of primary breast cancers fail to activate Smad2, indicating the presence of a TGF-Beta receptor defect.

Transforming Growth Factor- ß in Cancer Therapy, Vols. 1 and 2, provides a compendium of findings about the role of transforming growth factor- ß (TGF- ß) in cancer treatment and therapy. The first volume, Basic and Clinical Biology, is divided into three parts. This volume’s companion, Cancer Treatment in Therapy, examines transforming growth factor- ß in other developing and advanced cancers and methods of treatment and therapy.

Cancer Genetics is a collection of chapters covering the key recent developments in cancer genetics which have an impact on clinical care. The target audience will be physicians and scientists who need to be apprised on the most recent developments in the field.

This project addresses the question whether and, if so, how molecular lesions of the genes involved in the TGFB signaling pathway contribute to the origin and/or progression of breast cancer. We have cloned and determined the intron-exon structure of the TGFB type I receptor (TBR-I). This has allowed us to study this gene in a series of primary breast cancer specimens. Our most important finding is a much higher frequency of an exon 1 receptor variant among breast cancer cases than controls. Secondly, we have identified a serine to tyrosine mutation within the catalytic core of the TBR-I serine-threonine kinase domain in 2 of 31 primary and 5 of 12 metastatic breast cancer specimens. Thirdly, we have developed transient transfection as says to determine how specific TBR mutations affect receptor function. Using these assays we have shown that two previously identified TBR-II missense mutants are incapable of signaling because of the near complete loss of receptor kinase activity. Plans for the coming year include completing structural analyses of the TBR-I and -II genes in primary and metastatic breast cancer and defining the functional properties of the newly discovered TBR-I variant and mutant.

Transforming growth factor-[beta] (TGF-[beta]), identified nearly three decades ago, is a secreted polypeptide that functions in critical cell cycle processes, including cellular proliferation, differentiation, and development: It belongs to a large protein family that, in humans, contains 33 members, including activins, inhibins, bone morphogenetic proteins, growth and differentiation factors, and Mullerian inhibiting substance. This volume draws on the world's leading laboratories to comprehensively cover all aspects of the biology of TGF-[beta] and related factors. In addition to providing historical and background information, it describes the cell biology and signaling pathways of TGF-[beta] members in detail, including the roles of TGF-[beta] factors in the development and physiology of humans and model organisms. The last few chapters are devoted to the role of TGF-[beta] members in cancer and other diseases, as well as the possibilities for therapeutics based on knowledge of signaling pathways and macromolecular structures. It serves as a comprehensive reference work for both specialists and researchers less familiar with the field.

Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates

The MD Anderson Solid Tumor Oncology series presents cutting-edge surgical treatment and medical therapy for specific sites. This volume, Pancreatic Cancer, addresses epidemiology and molecular biology, inherited syndromes, staging, surgical techniques, multimodality therapy, and emerging therapies. The individual chapters focus on narrow, specific topics to produce a reference work of value to those interested in pancreatic cancer from a clinical and translational research perspective. A must-have for surgical oncologists and general surgeons.