Beyond explanation, the cancer biology patchwork

At present, the biology of breast cancer remains poorly understood. Currently, lymph node metastases, tumor grade, and size, and expression of hormone receptors provide the only true prognostic and predictive factors related to clinical outcome and response to treatment, respectively. Many other potential candidates have been suggested but, due to their limited predictive power, have not been widely accepted by the general oncological community. These histopathological features do not allow us any insight into breast cancer biology, however, and these prognostic classifications are far from perfect. At present, due to these limitations many clinicians consider prescribing adjuvant treatment to many women with early breast cancer to reduce the risk of relapse, only to benefit a few, thus exposing many patients to unnecessary toxicity. Since the publication of the complete sequence of the human genome however, a new era of research has begun [1]. More than 3 billions base pairs form the 30,000-40,000 genes that code all the required genetic information of a particular individual. The functions of the vast majority of these genes are still unknown. A combination of circumstances, including the advent of array-based technology and progress in the human genome initiative, have provided the ideal opportunity to begin efforts aimed at performing comprehensive molecular and genetic profiling of human cancers. The ability to interrogate tens of thousands of genes simultaneously by using microarray technologies has significantly changed our approach to the analysis of expression profiles, and has also led to an increased understanding of the basic biology of breast cancer. Such comprehensive technologies permit the assessment not only of individual genes, but also of clusters of genes that are coordinately expressed to generate "fingerprints" of biological states of the cells of origin. This is especially important given that it has become increasingly evident that the biology of cancer, particularly solid tumors, is determined by the behavior of many genes, rather than a few. Although there are other techniques that analyze differences in gene expression, none matches the ease and the comprehensive nature of the interrogation associated with c-DNA- or oligonucleotide-based microarray analysis. A list of the terms commonly used in this field is given in Table 30.1. (Table presented). © Springer-Verlag Berlin Heidelberg 2006.

Apoptosis ensures tissue homeostasis in response to developmental cues or cellular damage. Recently reported genome-wide RNAi screens have suggested that several metabolic regulators can modulate caspase activation in Drosophila. Here, we establish a previously unrecognized link between metabolism and Drosophila apoptosis by showing that cellular NADPH levels modulate the initiator caspase Dronc through its phosphorylation at S130. Depletion of NADPH removed this inhibitory phosphorylation, resulting in the activation of Dronc and subsequent cell death. Conversely, upregulation of NADPH prevented Dronc-mediated apoptosis upon DIAP1 RNAi or cycloheximide treatment. Furthermore, this CaMKII-mediated phosphorylation of Dronc hindered Dronc activation, but not its catalytic activity. Blockade of NADPH production aggravated the death-inducing activity of Dronc in specific neurons, but not in the photoreceptor cells of the eyes of transgenic flies; similarly, non-phosphorylatable Dronc was more potent than wild type in triggering specific neuronal apoptosis. Our observations reveal a novel regulatory circuitry in Drosophila apoptosis, and, as NADPH levels are elevated in cancer cells, also provide a genetic model to understand aberrations in cancer cell apoptosis resulting from metabolic alterations.

Chapter 1 - Childhood Cancer and Developmental Biology: A Crucial Partnership

AP-2γ regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription

Research Article| January 01 1987 Advances in Cancer Biology Steven B. Oppenheimer Steven B. Oppenheimer Search for other works by this author on: This Site PubMed Google Scholar The American Biology Teacher (1987) 49 (1): 11–15. https://doi.org/10.2307/4448409 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Steven B. Oppenheimer; Advances in Cancer Biology. The American Biology Teacher 1 January 1987; 49 (1): 11–15. doi: https://doi.org/10.2307/4448409 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentThe American Biology Teacher Search This content is only available via PDF. Copyright 1987 The National Association of Biology Teachers Article PDF first page preview Close Modal You do not currently have access to this content.

Cancer is one of the major non-communicable diseases (NCD) worldwide, accounting for 22% deaths in 2012 worldwide. The number of cases is projected to increase to 17 million by 2020. According to ICMR, almost half of the cases will be in Asia with more than 17 lakh cases expected to occur in India by 2020. In such a scenario, early diagnosis and cost-effective treatment will play a major role in effective patient management. Developing the infrastructure required to cater to a vast population requires substantial effort in research and development. The National Symposium on “An Integrated Approach to Diagnosis and Therapy in Cancer” aims to create awareness about cancer etiology and stimulate the interest of students in cancer research. It has become unequivocally evident that tumor development depends on the intricate reciprocal interplay of tumor cells with their local and distant environments. Mutations in genes regulating cell cycle/cell proliferation can also contribute to tumorigenesis and is of great relevance in both diagnosis and disease management. One of the major focus of the symposia is developing diagnostics and therapeutics through translational research. The invited speakers will make presentations on emerging areas in cancer research like nanomedicine, personalized medicine, etc. Reputed clinicians and researchers will provide different perspectives on cancer biology. Thus, this symposium aims at a comprehensive functional understanding on the integrated role of physical and life sciences in diagnostics and therapeutics of cellular and molecular events that are responsible for the plasticity of tumor cells. Moreover, it will bring together experts in cancer and molecular biology who will share their expertise on a new generation of effective diagnostic tools and therapeutic approaches in cancer. One of the objectives of the symposium is to provide students and researchers with a platform for the exchange of knowledge and innovative ideas towards a comprehensive approach in cancer biology. It provides them with an ample opportunity to present their research work related to the conference theme.

Spontaneous tumors in dogs and cats are appropriate and valid model tumor systems available for testing cancer therapeutic agents or studying cancer biology. The pet population is a vastly underutilized resource of animals available for study. Dogs and cats develop spontaneous tumors with histopathologic and biologic behavior similar to tumors that occur in humans. The tumors with potential relevance for human cancer biology include osteosarcoma, mammary carcinoma, oral melanoma, oral squamous cell carcinoma, nasal tumors, lung carcinoma, soft tissue sarcomas, and malignant non-Hodgkin's lymphoma. Canine osteosarcoma is a malignant aggressive bone tumor with a 90% metastasis rate after surgical amputation. Its predictable metastatic rate and pattern and its relative resistance to chemotherapy make this tumor particularly attractive for studying anti-metastasis approaches. Canine and feline malignant mammary tumors are fairly common in middle-aged animals and have a metastatic pattern similar to that in women; that is, primarily to regional lymph nodes and lungs. Chemotherapy has been minimally effective, and these tumors may be better models for testing biological response modifiers. Oral tumors, especially melanomas, are the most common canine malignant tumor in the oral cavity. Metastasis is frequent, and the response to chemotherapy and radiation has been disappointing. This tumor can be treated with anti-metastatic approaches or biological response modifiers. Squamous cell carcinomas, especially in the gum, are excellent models for radiation therapy studies. Nasal carcinomas are commonly treated with radiation therapy. They tend to metastasize slowly, but have a high local recurrence rate. This tumor is suitable for studying radiation therapy approaches. Primary lung tumors and soft tissue sarcomas are excellent models for studying combined modality therapy such as surgery with chemotherapy or biological response modifiers. Finally, non-Hodgkin's lymphoma is a common neoplastic process seen in the dog. These tumors respond to combination chemotherapy and have great potential as a model for newer chemotherapeutic agents and biological response modifiers. This paper will further elaborate on the relative merits of each tumor type as a model for human cancer therapy and biology.

Nearly all residents from accredited radiation oncology residency programs in the United States are required to take the American College of Radiology (ACR) In-Training examination each year. The test is comprised of three sections: Clinical Radiation Oncology, Radiological Physics, and Radiation (and Cancer) Biology. Here we provide an update on changes to the biology portion of the ACR exam. We also discuss the availability and use of the ACR and biology practice exams as assessment and teaching tools for both the instructors of radiation and cancer biology and the residents they teach.

Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n = 22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n = 13), benign neurofibromas (NF) (n = 26) and MPNST (n = 6). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 – strongly expressed in NF1-related tumours – caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1.

Annals of the New York Academy of SciencesVolume 886, Issue 1 p. 208-211 Melanoma Cell Lines Contain a Proteasome-Sensitive, Nuclear Cytoskeleton-Associated Pool of β-Catenin P. BONVINI, Corresponding Author P. BONVINI Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850 (P.B. & L.N.) and Bethesda, Maryland 20892 (S.-G.H. & J.T.), USA Address for correspondence: Paolo Bonvini, 9610 Medical Center Drive, Suite 300, Rockville, Maryland 20850. Phone, 301/402–3128, ext. 312; fax, 301/402-4422. e-mail, [email protected]Search for more papers by this authorS.-G. HWANG, S.-G. HWANG Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850 (P.B. & L.N.) and Bethesda, Maryland 20892 (S.-G.H. & J.T.), USASearch for more papers by this authorM. EL-GAMIL, M. EL-GAMIL Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this authorP. ROBBINS, P. ROBBINS Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this authorL. NECKERS, L. NECKERS Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850 (P.B. & L.N.) and Bethesda, Maryland 20892 (S.-G.H. & J.T.), USASearch for more papers by this authorJ. TREPEL, J. TREPEL Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850 (P.B. & L.N.) and Bethesda, Maryland 20892 (S.-G.H. & J.T.), USASearch for more papers by this author P. BONVINI, Corresponding Author P. BONVINI Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850 (P.B. & L.N.) and Bethesda, Maryland 20892 (S.-G.H. & J.T.), USA Address for correspondence: Paolo Bonvini, 9610 Medical Center Drive, Suite 300, Rockville, Maryland 20850. Phone, 301/402–3128, ext. 312; fax, 301/402-4422. e-mail, [email protected]Search for more papers by this authorS.-G. HWANG, S.-G. HWANG Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850 (P.B. & L.N.) and Bethesda, Maryland 20892 (S.-G.H. & J.T.), USASearch for more papers by this authorM. EL-GAMIL, M. EL-GAMIL Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this authorP. ROBBINS, P. ROBBINS Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USASearch for more papers by this authorL. NECKERS, L. NECKERS Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850 (P.B. & L.N.) and Bethesda, Maryland 20892 (S.-G.H. & J.T.), USASearch for more papers by this authorJ. TREPEL, J. TREPEL Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850 (P.B. & L.N.) and Bethesda, Maryland 20892 (S.-G.H. & J.T.), USASearch for more papers by this author First published: 06 February 2006 https://doi.org/10.1111/j.1749-6632.1999.tb09418.xCitations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume886, Issue1ANTICANCER MOLECULES: STRUCTURE, FUNCTION, AND DESIGNDecember 1999Pages 208-211 RelatedInformation

Aging is accompanied by several age-related disorders leading to death of living beings. These age-related disorders and pathological conditions may also include the development of cancer. Cancer is a chronic disease, and many changes at cellular, molecular, and physiological levels that occur during aging affect the biology of cancer. There are several phenomena which are common between cancer and aging such as telomere shortening, genomic instability, senescence, global hypomethylation, promoter-specific hypermethylation, metabolism, and autophagy. Hence, the association between biology of cancer and aging is incontrovertible; however, the underlying molecular mechanisms could be similar or different. Understanding the common cellular and molecular biology of stem and progenitors cells in cancer and aging will undoubtedly help in exploring novel targets that could be used as a therapy and thus can improve the early detection and treatment of aging-associated pathologies such as cancer.

Studying the naturally occurring skin cancers seen in companion (pet) animals provides an opportunity to improve our knowledge about the biology, epidemiology, pathogenesis, and treatment of skin cancer across species, contributing to advances in human and animal health through a comparative oncology approach. A comparative oncology approach to the study of skin cancer integrates knowledge and studies of these naturally occurring cancers in pets with other basic and clinical research. Studying the similarities and the differences between neoplastic conditions of animals and humans can provide additional knowledge and insight into the biology of cancer. This chapter reviews the clinical features, pathology, and molecular biology associated with the common skin cancers seen in animals, focusing on the similarities and differences between animals and humans.

Compelling evidence about the differences in the biology and behavior of invasive breast cancer between African-American (AA) and White-American (WA) women motivate inquiry into comparing the clinicopathology of non-invasive breast cancer (ductal carcinoma in situ, DCIS). AA and WA women diagnosed with their first primary DCIS between 1990 and 1999 were identified from the institutional tumor registry. Data on method of presentation, treatment, and patient characteristics were retrieved from electronic medical records. Patients were followed up through the medical records until the diagnosis of a subsequent cancer or the last day of contact with the institution. A total of 100 (29.6%) AAs and 236 (70.4%) WAs with the mean age of 60 (SD ± 13) and 57 (SD ± 12), respectively, contributed to this study. DCIS was detected during routine screening mammography for 81% (n = 81) of AAs and 88.4% (n = 206) of WAs (P = 0.073). Differences in the distributions of grade, margin status, necrosis, or treatment modalities were not statistically significant between AAs and WAs. Analysis of competing risks Cox proportional hazard multivariate modeling yielded a significant 8-year cumulative risk of a second cancer for AAs but only in the ipsilateral breast (HR = 3.96, 95% CI 1.42-11.04, P = 0.01). Despite comparable clinical presentation and treatment, 8 years after the initial treatment, AAs experienced a higher risk of second breast cancer in ipsilateral but not in the contralateral breast. The observed excess risk of a second cancer in the ipsilateral breast may suggest of intrinsic differences in the biology of cancer.

At present, most cases of unresectable cancer cannot be cured. Genetic mutations, EMT, and cancer stem cells are three major issues linked to poor prognosis in such cases, all connected by inter- and intra-tumor heterogeneity. Issues on inter-/intra-tumor heterogeneity of genetic mutation could be resolved with recent and future technologies of deep sequencers, whereas, regarding such issues as the "same genome, different epigenome/phenotype", we expect to solve many of these problems in the future through further research in stem cell biology. We herein review and discuss the three major issues in the biology of cancers, especially from the standpoint of stem cell biology.

The biology of cancer by R. A. Weinberg