Uncontrolled cell proliferation is the hallmark of cancer, and tumor cells have typically acquired damage to genes that directly regulate their cell cycles. Genetic alterations affecting p16(INK4a) and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein (RB) and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development. Like the tumor suppressor protein p53, components of this "RB pathway," although not essential for the cell cycle per se, may participate in checkpoint functions that regulate homeostatic tissue renewal throughout life.

http://science.sciencemag.org/content/sci/274/5293/1672.full.pdf

Cancer Cell Cycles

Objective. —To identify and quantify the major external (nongenetic) factors that contribute to death in the United States. Data Sources. —Articles published between 1977 and 1993 were identified through MEDLINE searches, reference citations, and expert consultation. Government reports and compilations of vital statistics and surveillance data were also obtained. Study Selection. —Sources selected were those that were often cited and those that indicated a quantitative assessment of the relative contributions of various factors to mortality and morbidity. Data Extraction. —Data used were those for which specific methodological assumptions were stated. A table quantifying the contributions of leading factors was constructed using actual counts, generally accepted estimates, and calculated estimates that were developed by summing various individual estimates and correcting to avoid double counting. For the factors of greatest complexity and uncertainty (diet and activity patterns and toxic agents), a conservative approach was taken by choosing the lower boundaries of the various estimates. Data Synthesis. —The most prominent contributors to mortality in the United States in 1990 were tobacco (an estimated 400000 deaths), diet and activity patterns (300 000), alcohol (100 000), microbial agents (90 000), toxic agents (60 000), firearms (35 000), sexual behavior (30 000), motor vehicles (25 000), and illicit use of drugs (20 000). Socioeconomic status and access to medical care are also important contributors, but difficult to quantify independent of the other factors cited. Because the studies reviewed used different approaches to derive estimates, the stated numbers should be viewed as first approximations. Conclusions. —Approximately half of all deaths that occurred in 1990 could be attributed to the factors identified. Although no attempt was made to further quantify the impact of these factors on morbidity and quality of life, the public health burden they impose is considerable and offers guidance for shaping health policy priorities. (JAMA. 1993;270:2207-2212)

https://jamanetwork.com/journals/JAMA/articlepdf/409171/jama_270_18_038.pdf

Actual causes of death in the United States.

Endostatin: an endogenous inhibitor of angiogenesis and tumor growth.

NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

Background Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. Methods We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first. Results

/pdf/platinum-based-chemotherapy-plus-cetuximab-in-head-and-neck-2c129qnqh9.pdf

Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer

Reduction of lethal graft-versus-host disease: transplantation of cultured murine bone marrow across minor histocompatibility differences

Lethal Graft-Versus-Host Disease: Modification With Allogeneic Cultured Donor Cells

PRESENTATION OF CASE First admission. A 17-year-old girl was referred to the hospital because of hilar lymphadenopathy. She had been well until 10 days previously, when there was the onset of a sha...

Case 31-1970

As I read the paper \"Sector Resection With or Without Postoperative Radiotherapy for Stage I Breast Cancer: A Randomized Trial,\" by Holmberg and colleagues (/), I found myself distressed that it had been accepted for publication, since I believe that it is premature to make the interpretations for which the study was designed and that the authors make. While not changing my view on premature interpretation, I have, on reflection, somewhat modified my opinion as to the appropriateness of publication at this time. The focus of this study is to determine whether, with careful selection of discrete lesions combined with a surgical technique designed to encompass them with pathologically determined free margins, it is possible to spare patients postoperative radiotherapy of the breast and still avoid local recurrence. A second question is whether a difference in the likelihood of local recurrence will result in a concomitant difference in distant metastasis and, ultimately, in survival.

It's Too Soon To Know

Background: Cancer staging and treatment presumes a division into localized or metastatic disease We proposed an intermediate state defined by β5 cumulative metastasis(es), termed oligometastases In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments However, many patients who initially present with oligometastases progress to polymetastases Predictors of progression could improve patient selection for metastasis-directed therapy Methods: Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy Results: Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression Conclusions: These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment Citation Format: {Authors} {Abstract title} [abstract] In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3405 doi:1538-7445AM2012-3405

Samuel Hellman

Papers

Reduction of lethal graft-versus-host disease: transplantation of cultured murine bone marrow across minor histocompatibility differences

Lethal Graft-Versus-Host Disease: Modification With Allogeneic Cultured Donor Cells

Case 31-1970

It's Too Soon To Know

Abstract 3405: MicroRNA expression characterizes oligometastasis(es)