Oncogenes in Human Cancer Oncogenes of the kind found in human cancers were initially discovered through their presence in the genome of retroviruses capable of causing cancers in chickens, mice, and rats. The cellular homologues of these viral genes are often targets of mutation or aberrant regulation in human cancer. Whereas many oncogenes were discovered because of their presence in retroviruses, other oncogenes, particularly those involved in translocations characteristic of particular leukemias and lymphomas, were isolated through genomic approaches.
The European Union’s CAREX database of occupational exposures to
carcinogens estimated that in the early 1990s 22-24 million workers in the
then 15 EU member states were exposed to carcinogens classiﬁed as group 1
by the International Agency for Research on Cancer – those known to cause
cancer in humans.
Overall, 32 million workers, 23 per cent of the working population,
had workplace exposures associated by the CAREX database with an
occupational cancer risk.
Risk mapping Draw a basic map of the workplace, marking on it the
machines, workstations and the substances or processes used. Record on
the risk map any health problems reported by workers doing particular jobs.
Repeat the exercise periodically and see if any problems become apparent.
If cancer causing substances or processes are being used, investigate
alternatives and, if this is not possible, safer work methods.
Body mapping Draw two body outlines on a large piece of paper, one
representing the front of a person, one the back.
According to the National Cancer Institute, cancer continues to take
a devastating toll. Among women in the United States, cancer is the
second-leading cause of death after heart disease. Medical researchers
fighting against cancer have made significant progress, however. In
recent years, cancer incidence rates have been stable, and—although
the annual rate of decline in cancer death rates among men have been
twice as large as the declines in women—mortality has decreased for
ten of the top 15 cancers in women.
For decades we have been learning about the interplay between tumors and the
immune system. Our knowledge seemed somewhat incomplete and indirect, like
listening to the ocean waves through a shell. Only recently, cancer immunotherapy has
started to become a reality, with Provenge (Dendreon Corporation, WA), an
autologous antigen-presenting cell preparation, earning the approval of United States
Food and Drug Administration (FDA) for the treatment of advanced prostate cancer in
Specific micronutrient deficiencies may affect maternal and foetal health. Iodine deficiency
during pregnancy may cause foetal brain damage and mental retardation in infants. Vitamin
A deficiency increases the risk in pregnant women of infection and anaemia, may cause
blindness during pregnancy and early lactation, and has been associated to an elevated risk of
HIV mother-to-child transmission. Folate deficiency may cause severe foetal neural tube
defects like anencephaly and spina bifida.
Lung cancer is the leading cause of cancer death among men and women in
the United States with 170,000 deaths per year. This exceeds the sum of the
next three leading causes of death due to cancer: breast, colon, and prostate.
There are over 1 million deaths worldwide due to lung cancer, making it truly
an epidemic. Fewer than 15% achieve a 5-yr survival. The vast majority (85%)
present with advanced disease, although stage I patients may have a 5-yr
survival approaching 70% (1).
Pancreatic cancer is one of the most fatal human malignancies with extremely poor
prognosis making it the fourth leading cause of cancer-related deaths in the United
States. The molecular mechanisms of pancreatic carcinogenesis are not well
understood. The major focus of these two books is towards the understanding of the
basic biology of pancreatic carcinogenesis, identification of newer molecular targets
and the development of adjuvant and neoadjuvant therapies.
Harrison's Internal Medicine Chapter 82. Infections in Patients with Cancer
Infections in Patients with Cancer: Introduction Infections are a common cause of death and an even more common cause of morbidity in patients with a wide variety of neoplasms. Autopsy studies show that most deaths from acute leukemia and half of deaths from lymphoma are caused directly by infection. With more intensive chemotherapy, patients with solid tumors have also become more likely to die of infection.
Carcinoma of the lung is the most common cause of cancer-related death in men and women.
Prognosis correlates strongly with stage of disease at presentation and to some degree with
the histological subtype of the tumor. Histological classifications of lung cancer were somewhat
arbitrary and a matter of convenience. However, multiple lines of differentiation are
often found within a single tumor, if it is sufficiently sampled.
Lung cancer is the most frequent cause of cancer deaths in both men and
women in the U.S. (1). Although tobacco smoking is accepted as the number
one cause of this devastating disease, our understanding of the acquired genetic
changes leading to lung cancer is still rudimentary. Lung cancer is classifi ed
into two major clinic-pathological groups, small cell lung carcinoma (SCLC)
and non-small cell lung carcinoma (NSCLC) (2). Squamous cell carcinoma,
adenocarcinoma, and large cell carcinoma are the major histologic types of
Telomerase DNA polymerase is unable to replicate the tips of chromosomes, resulting in the loss of DNA at the specialized ends of chromosomes (called telomeres) with each replication cycle. At birth, human telomeres are 15- to 20-kb pairs long and are composed of tandem repeats of a six-nucleotide sequence (TTAGGG) that associate with specialized telomere-binding proteins to form a T-loop structure that protects the ends of chromosomes from being mistakenly recognized as damaged.
In developed countries, cancer is the second leading cause
of death exceeded only by cardiovascular diseases. There are
more than 100 types of cancers that can inflict any part of the
body. In 2005, 7.6 million people died of cancer, which constitutes
13% of the 58 million deaths worldwide. Approximately,
1.3 million people are diagnosed each year with cancer in the
United States, and ~ 1500 of them die every day.
Squamous cell carcinoma of the head and neck affects more than
40,000 people each year in the U.S., and at least 13,000 people each year die
of this disease. In many countries, oral cancers are one of the leading causes
of cancer incidence, and a major cause of morbidity and mortality. Sadly,
these statistics have not improved despite clear delineation of tobacco and
alcohol as contributory or etiologic in at least 80% of cases.
Death and Dying The most common causes of death in patients with cancer are infection (leading to circulatory failure), respiratory failure, hepatic failure, and renal failure. Intestinal blockage may lead to inanition and starvation. Central nervous system disease may lead to seizures, coma, and central hypoventilation. About 70% of patients develop dyspnea preterminally. However, many months usually pass between the diagnosis of cancer and the occurrence of these complications, and during this period the patient is severely affected by the possibility of death. ...
Induction of p53 by the DNA damage and oncogene checkpoints.
In response to noxious stimuli, p53 and mdm2 are phosphorylated by the ataxia telangiectasia mutated (ATM) and related ATR serine/threonine kinases, as well as the immediated downstream checkpoint kinases, Chk1 and Chk2. This causes dissociation of p53 from mdm2, leading to increased p53 protein levels and transcription of genes leading to cell cycle arrest (p21Cip1/Waf1) or apoptosis (e.g., the proapoptotic Bcl-2 family members Noxa and Puma).
Antiangiogenic Therapy Understanding the molecular mechanisms that regulate tumor angiogenesis may provide unique opportunities for cancer treatment. Acquired drug resistance of tumor cells due to their high intrinsic mutation rate is a major cause of treatment failure in human cancers. ECs comprising the tumor vasculature are genetically stable and do not share genetic changes with tumor cells; the EC apoptosis pathways are therefore intact.
Clinical Presentation and Differential Diagnosis Most head and neck cancers occur after age 50, although these cancers can appear in younger patients, including those without known risk factors. The manifestations vary according to the stage and primary site of the tumor. Patients with nonspecific signs and symptoms in the head and neck area should be evaluated with a thorough otolaryngologic exam, particularly if symptoms persist longer than 2â€“4 weeks.
Cancer of the nasopharynx typically does not cause early symptoms.
Harrison's Internal Medicine Chapter 86. Breast Cancer
Breast Cancer: Introduction
Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast. In the year 2007, about 180,510 cases of invasive breast cancer and 40,910 deaths occurred in the United States. Epithelial malignancies of the breast are the most common cause of cancer in women (excluding skin cancer), accounting for about one-third of all cancer in women.
There have been a significant number of advances
in the field of cancer research since the
first edition of Cancer Biology, which was published
in 1981. These include advances in defining
the genetic and phenotypic changes in cancer
cells, the genetic susceptibility to cancer, molecular
imaging to detect smaller and smaller tumors,
the regulation of gene expression, and the
‘‘-omics’’ techniquesofgenomics, proteomics,and
metabolomics, among others.