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

Part I: Molecular Biology of Cancer Molecular Methods in Oncology Section 1. Amplification Techniques Section 2. RNA Interference Section 3. cDNA arrays Section 4. Tissue arrays Section 5. Cytogenetics Section 6. Bioinformatics Genomics and Proteomics Molecular Targets in Oncology Section 1. Signal transduction systems Section 2. Cell cycle Section 3. Apoptosis Section 4. Telomerase Invasion and Metastases Angiogenesis Cancer Immunology Part II: Principles of Oncology Etiology of Cancer: Viruses Section 1. RNA Viruses Section 2. DNA Viruses Etiology of Cancer: Chemical Factors Etiology of Cancer: Tobacco Etiology of Cancer: Physical Factors Epidemiology of Cancer Section 1. Epidemiologic Methods Section 2. Cancer Statistics Principles of Surgical Oncology Section 1. General Issues Section 2. Laparascopic Surgery Principles of Radiation Oncology Principles of Medical Oncology Pharmacology of Cancer Chemotherapy Section 2. Pharmocokinetics Section 3. Pharmacogenomics Section 4. Alkylating Agents Section 5. Cisplatin and its Analogues Section 6. Antimetabolites Section 7. Topoisomerase Interactive Agents Section 8. Antimicrotubule Agents Section 9. Miscellaneous Chemotherapeutic Agents Pharmacology of Cancer Biotherapeutics Section 1. Interferon Section 2. Interleukin 2 Section 3. Histone deacetylase inhibitors as differentiation agents Section 4. Monoclonal Antibodies Pharmacology of Endocrine Manipulation Design and Analysis of Clinical Trials Part III: Practice of Oncology Cancer Prevention: Preventing Tobacco-Related Cancers Cancer Prevention: Diet and Chemopreventive Agents Section 1. Dietary fat Section 2. Dietary Fiber Section 3. Dietary fruits and vegetables: naturally occurring anticarcinogens Section 4. Retinoids, carotenoids and micronutrients Section 5. Dietary Carcinogens Section 6. Cyclo-oxygenase inhibitors Section 7. Physical Activity and Body Weight Cancer Prevention: Role of Surgery in Cancer Prevention Cancer Screening Advanced Molecular Diagnostics Advanced Imaging Methods Section 1. Functional and Metabolic Imaging Section 2. Interventional Radiology Cancer Diagnosis: Endoscopy Section 1. Gastrointestinal endoscopy Section 2. Respiratory Tract Cancer of the Head and Neck Section 1. Molecular Biology of Head and Neck Tumors Section 2. Treatment of Head and Neck Cancers Section 3. Rehabilitation after Treatment for Head Cancer of the Lung Section 1. Molecular Biology of Lung Cancer Section 2. Non-small Cell Lung Cancer Section 3. Small Cell Lung Cancer Neoplasms of the Mediastinum Cancers of the Gastrointestinal Tract

Cancer : Principles and Practice of Oncology

Important advances in oncology

Karnofsky Memorial Lecture. Natural history of small breast cancers.

This study was undertaken to investigate the long-term survival and the probability of "cure" in a group of 644 patients treated by mastectomy for T1 breast carcinoma. After a median follow-up of 18.2 years, 23% were dead of recurrent breast carcinoma, 3% were alive with recurrent disease, and 74% had not experienced a recurrence. The probability of recurrence was directly related to the initial extent of the disease. Overall, 16% of recurrences and 25% of deaths due to disease occurred in the second decade of follow-up. The proportion of recurrences detected in the second decade was inversely related to the stage of the primary tumor at diagnosis. When stratified by tumor size, T1N0M0 patients with tumors 1.0 cm or less in diameter had a significantly better 20-year recurrence-free survival (86%) than did T1N0M0 patients with tumors 1.1 to 2.0 cm (69%). When observed and expected survival curves were compared by the method of Brinkley and Haybittle, it appeared that 80% of T1N0M0 patients with tumors 1 cm or less might be cured at 20 years, whereas for those in the 1.1- to 2-cm group, the proportion cured was indeterminate, but might be as high as 70%. A potentially cured group could not be identified among T1N1M0 patients, but an estimated 52% of these patients did not have a recurrence within the nearly 20-year follow-up period. These data are important when one considers the proper role of adjuvant therapy for stage I disease. Patients with tumors larger than 1 cm and those with axillary lymph node metastases may have an improved recurrence-free survival as a result of systemic adjuvant treatment, while women in the T1N0M0 group with an especially favorable recurrence-free survival, particularly those with tumors 1 cm in diameter or smaller, might be spared adjuvant therapy.

A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma.

Prognostic factors have been examined in 644 patients with tumor-node-metastasis (TNM) stage T1 breast carcinoma treated by mastectomy and followed for a median of 18.2 years. Overall, 148 patients (23%) died of recurrent breast carcinoma. Eighteen (3%) were alive with recurrent disease and 478 (74%) were alive or died of other causes without recurrence. Unfavorable clinicopathologic features were larger tumor size (1.1 to 2.0 cm v less than or equal to 1 cm), perimenopausal menstrual status, the number of axillary lymph node metastases, poorly differentiated grade, presence of lymphatic tumor emboli (LI) in breast tissue near the primary tumor, blood vessel invasion (BVI), and an intense lymphoplasmacytic reaction around the tumor. Median survival after recurrence for the entire series was 2 years. This was not significantly influenced by tumor size, the number of axillary nodal metastases, the type of treatment for recurrence, or the interval to recurrence. The proportions surviving 5 and 10 years after recurrence were 17% and 5%, respectively. Among T1N0M0 cases, the chance of a local recurrence was 2.8% within 20 years. Median survival of T1N0M0 cases after local recurrence (4.5 years) was significantly longer than after systemic recurrence (1.5 years). A similar trend (3.7 v 2.0 years), not statistically significant, was seen in T1N1M0 patients, who had a 6.5% chance of local recurrence within 20 years. Median survival following systemic recurrence detected 10 or more years after diagnosis in T1N0M0 and in T1N1M0 patients was significantly longer than the median survival for systemic recurrences found in the first decade of follow-up. This difference did not apply following local recurrence in either T1N0M0 or T1N1M0 cases. It is evident that patients with T1 breast carcinoma can be subdivided into differing prognostic groups and this must be taken into account when considering the role of adjuvant chemotherapy for stage I disease. Systemic adjuvant treatment may prove to be beneficial for patients with unfavorable prognostic factors, while women with an especially low risk for recurrence (eg, T1N0M0 tumor 1.0 cm or less) might be spared such treatment.

Samuel Hellman

Papers

Cancer : Principles and Practice of Oncology

Important advances in oncology

Karnofsky Memorial Lecture. Natural history of small breast cancers.

A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma.

Pathological prognostic factors in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma: a study of 644 patients with median follow-up of 18 years.