The data reviewed here suggest that telomere dynamics and telomerase expression are fundamentally involved in cellular aging and cancer. Of particular importance is the stabilization of telomeres by activation of telomerase and the association of this process with cell immortality and human malignancies. Thus, we believe that cell immortalization is required for long-term growth of the vast majority of malignant or metastatic tumors and that advances in telomere biology and telomerase inhibition will improve the way cancers are diagnosed and treated. We look forward to the clinical evaluation of these bold predictions.
The Breast JournalVolume 3, Issue 5 p. 246-260 Is Axillary Lymph Node Dissection Necessary in Routine Management of Breast Cancer? No. Blake Cady M.D., F.A.C.S., Corresponding Author Blake Cady M.D., F.A.C.S. Department of Surgery, Harvard Medical School, Boston, Massachusetts, and Department of Surgery, Brown University, Providence, Rhode IslandAddress correspondence and reprint requests to: Blake Cady, M.D., F.A.C.S., Women & Infants' Hospital of Rhode Island, 101 Dudley Street, Providence, RI 02905-2499, U.S.A.Search for more papers by this author Blake Cady M.D., F.A.C.S., Corresponding Author Blake Cady M.D., F.A.C.S. Department of Surgery, Harvard Medical School, Boston, Massachusetts, and Department of Surgery, Brown University, Providence, Rhode IslandAddress correspondence and reprint requests to: Blake Cady, M.D., F.A.C.S., Women & Infants' Hospital of Rhode Island, 101 Dudley Street, Providence, RI 02905-2499, U.S.A.Search for more papers by this author First published: 30 January 2007 https://doi.org/10.1111/j.1524-4741.1997.tb00180.xCitations: 15AboutPDF 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 Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume3, Issue5September 1997Pages 246-260 RelatedInformation
The clinical and experimental work suggests the following scheme for the pathogenesis of gastric lymphoma. The first step is accumulation of lymphoid tissue (MALT) in response to infection of the stomach by H. pylori. In rare instances, this lymphoid infiltrate contains cells with a growth advantage, possibly because of a genetic change (trisomy 3?). The result is a monoclonal lymphoproliferative lesion that is responsive to H. pylori-driven T-cell help. Further genetic changes [t(1;14)?] may lead to escape from T-cell dependency and, ultimately, high-grade transformation. Low-grade B-cell gastric lymphoma serves as the paradigm for the entire group of MALT lymphomas that occur in a wide variety of extranodal sites. It is likely that the growth of this group of lymphomas is governed by a series of different antigens, many of which, like H. pylori, might be microbiologic. The challenge is to identify these agents and apply this knowledge to the treatment of other MALT lymphomas. This work also emphasizes the importance of paying attention to the histologic structure and nature of the ancillary cells in low-grade B-cell lymphomas. These cells, particularly the T cells, are not accidental passengers or necessarily representative of a "host response" to the neoplastic B cells. In low-grade MALT lymphomas, they are vital for the survival of the tumor. Similar mechanisms may be operative in nodal low-grade B-cell lymphomas and could offer new approaches to therapy.
Pleural mesotheliomas and osteosarcomas develop in hamsters injected intracardially with SV40. Using primers specific for the RB-pocket binding domain of SV40 we analysed with the polymerase chain reaction frozen specimens from 48 human mesotheliomas and 145 human bone tumours. We found that 60% of human mesotheliomas and 33% of human bone tumours contained SV40-like DNA. Immunostaining, Western blot and RNA in situ hybridization experiments revealed SV40 Tag expression in human mesotheliomas. Osteosarcomas were not studied for Tag expression because not enough material was available. Finally, antibodies anti-Tag were detected in the sera collected from patients with mesothelioma. These data indicate that SV40, or a closely related virus, is/are present in human mesothelioma and osteosarcoma.
Chemoprevention refers to the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent the progression to invasive cancer. The ideal chemopreventive agent is safe and nontoxic over the long term. It should be easy to take and demonstrated to be effective in randomized trials in humans. Aspirin and NSAIDs meet many of the criteria for an ideal agent. The literature on aspirin and NSAIDs makes it clear that these agents can prevent colorectal cancer and precursor adenomas. That does not mean that we should make general recommendations for their use. First, we do not know the proper dose or duration. More important, these medications are accompanied by adverse effects that can be considerable. Indeed, the Medical Letter, an authoritative, unbiased publication on drugs and therapeutics, concluded that "for primary prevention in low-risk patients, more studies are required to establish whether the beneficial effect of aspirin is great enough to compensate for the possible increased risk of hemorrhagic stroke." These recommendations were directed at the use of these medications for prevention of myocardial infarction, but the same conclusions apply to colorectal cancer: although aspirin may prevent the disease, it may increase the risk of hemorrhagic strokes or cause other adverse effects. We must accurately balance the benefits and risks of these drugs, based on the results of ongoing randomized studies, before recommending aspirin for prevention of colorectal cancer. Is there anything that we can recommend to our patients for prevention of colorectal cancer? Based on observational epidemiologic studies, it is clear that individuals who consume a diet high in vegetables and natural fibers and low in fat have a reduced risk of colon cancer and polyps. Optimal nutrient intakes for the prevention of cancer might be more readily achieved via food fortification or supplementation, but this requires more research. Regular physical exercise and maintenance of normal body weight are also protective. Until the results of definitive studies of chemopreventive agents are available, we can recommend that our patients eat a sensible diet, exercise, and avoid obesity. Such an approach should protect them from cardiovascular disease, an even deadlier condition than colorectal cancer. In the future, we need randomized prevention trials that, for logistic reasons, may need to focus on the occurrence and progression of colorectal adenomas rather than carcinoma itself. Studies that test more than one compound at a time, using factorial designs, will be more efficient. We will need better information about duration and dose, adverse side effects, molecular mechanisms, and cellular sites of NSAID activity. Ultimately, we will need to know more about the biology and molecular biology of colorectal cancer and its precursors. That information will, perhaps, permit us to design agents to interrupt the pathway to cancer and to use intermediate markers more intelligently.
Angiogenesis is a critical process for the growth and metastatic properties of all solid tumors. Recent biological and molecular studies have begun to elucidate the basic mechanisms of vascular cell proliferation, motility, and differentiation in vitro and in vivo. With this knowledge, it should be feasible to devise therapeutic strategies to selectively target and perturb the biological processes of angiogenic vascular cells, thereby leading to effective inhibitors of angiogenesis. This strategy has led to the development of antagonists to integrin alpha v beta 3, which promote the unscheduled programmed cell death of newly sprouting blood vessels. These antagonists cause regression of preestablished human tumors growing in laboratory animals and thus may lead to an effective therapeutic approach for most solid tumors in humans. Studies are currently aimed at designing highly specific small organic integrin inhibitors that will disrupt the signals enabling vascular cells to respond to the tumor-associated extracellular environment and to promote tumor-induced angiogenesis.
Axillary dissection for primary operable cancer follows the basic tenets of surgical oncology and achieves the stated goals. Local control is excellent, with failure rates of 0% to 2%. Long-term, disease-free survival is improved with axillary dissection. It is often stated that axillary dissection is not required for the smallest lesions, but the 15% risk of axillary disease with the T1A lesion suggests otherwise. Axillary sampling would not achieve the stated goals because of the high probability of retained, potentially resectable disease in the node-positive group. Axillary recurrence is associated with unacceptably high morbidity and mortality rates. Although the survival is similar in the three treatment groups of NSABP B-04, the inordinately high systemic failure rate with axillary recurrence would suggest that more aggressive local control could prevent many of these failures. After all, long-term survival free of disease is reported in many series, even in patients with multiple involved nodes. Axillary dissection also generates the most accurate prognostic variable on which further therapeutic interventions are predicated. At present, no other diagnostic or therapeutic approach achieves all these goals. The value of the axillary dissection is to provide accurate prognostic information, provide excellent local control, and improve the survival rate in the node-positive group. Perhaps in the future, a diagnostic test such as PET scanning or sentinel node mapping will identify patients with a clear axilla, who therefore do not require an axillary dissection. There has yet to be a primary operable carcinoma that benefits from preservation of potentially fully resectable disease.
