Medical brain notes 30

  CANCER INTRODUCTION In multicellular organisms, the growth of cells by division is under tight control  Cells divide when stimulated with the requisite internal and external signals ( Figure 17.1 ). This strict control of cell division ensures that division occurs at a rate appropriate to the structure of the tissue or organ. In some tissues, for example bone marrow, skin and gastrointestinal (GIT) endothelium, cells divide constantly, replacing ones that have died. However, in other tissues, such as nervous tissue, mitosis is rare and lost cells are not replaced. In yet other tissues, cells can commence dividing when required as, for example, in the regeneration of liver or during the healing of wounds in the skin. The term  cancer  covers a number of diseases in which the growth of cells becomes uncontrolled. Cancer cells fail to respond to the usual controling signals and their growth becomes unregulated. Indeed, the name  cancer  comes from a Latin wo...

  CLASSIFICATION OF CANCER TYPES Cancers are often classified according to their tissue of origin. Thus, a carcinoma is derived from epithelial tissue, whereas a sarcoma is derived from tissue of mesodermal origin such as muscle, bone or cartilage. The term leukemia refers to tumors of the bone marrow that result in excess cells of a single type appearing in the blood. Lymphoma refers to a tumor which arises from lymphoid tissue, such as a lymph node. There is also a group of highly malignant tumors that occur in childhood, which all have the suffix ‘blastoma’. These include neuroblastomas, which arise in the neuroblasts of the adrenal medulla, retinoblastoma, which originates in the retina of the eye, and nephroblastoma, derived from the embryonic cells of the kidney.

  EPIDEMIOLOGY OF CANCER In England in 2002 there were 276 700 new cases of malignant cancer registered, approximately evenly divided amongst men and women. However, individual cancers are often unevenly distributed between the sexes and, clearly, some cancers occur only in men or women. Obvious examples of the latter are cancer of the  cervix uteri  or ‘cervical cancer’ in women and testicular and prostate cancer in men. Contrary to common belief, men can develop breast cancer, although the incidence is much lower than in women. Moreover, the incidence of breast cancer in both sexes appears to be increasing. A study in the USA showed increases in male and female breast cancer of 26% and 52% respectively between two separate studies in 1973– 1978 and 1994–1998. The commonest forms of cancer in men, women and children in the USA are shown in  Table 17.1 . The annual incidence of different forms of cancer is shown in  Figure 17.2 . With the exception of the childh...

  MOLECULAR BIOLOGY OF CANCER In 1914, Boveri (1862–1915) suggested that a malignant tumor arose from a cell that had acquired chromosomal abnormalities. In other words, cancer was caused by mutations in the DNA of cells. The multistep theory of cancer suggests that between five and seven successive mutations may have to occur before a cancer can develop ( Figure 17.4 ). Each successive mutation gives the cell a selective growth advantage over the normal cells which surround it. For example, one mutation may confer the ability to grow at a faster rate than normal cells. The cell would then proliferate to form a tissue which is said to be hyperplastic. One of the daughter cells may then undergo another mutation, which allows uncontrolled division of the progeny, to form a mass of cells which have abnormal morphology. At this stage the tumor is known as a carcinoma  in situ . Accumulation of further mutations within the clone may mean that the cells can detach from the tumor and...

  CAUSES OF CANCER The mutations that lead to cancerous states are caused by or associated with a number of factors. These include mutations caused by errors in replicating DNA or failures in repairing damaged DNA, or they may be induced by a variety of environmental agents, including chemical carcinogens and ionizing radiation or by the action of some viruses. Mutations in cancer associated germ-line genes may also mean that offspring carrying the gene are more susceptible to developing cancer. INHERITED CANCERS The association between the inheritance of a mutated gene and the development of cancer genes may be direct or indirect. For a direct association, the offspring must inherit a mutated gene which confers increased susceptibility to a specific type of cancer. With an indirect association, the inherited gene is associated with defective mechanisms for the repair of DNA that, in turn, leads to a greater likelihood of cancer. An example of the latter occurs in people with the d...

  GENERAL DIAGNOSIS OF CANCER The symptoms of cancer at presentation depend on the location and extent of the tumor. Depending on the cancer, symptoms may develop when the cancer is relatively small as, for example, when even a small tumor of the brain causes pressure to develop. Other tumors, such as those developing in the ovary may not produce symptoms until it is relatively large. A number of general signs may alert an individual to the presence of an undiagnosed tumor, for example, an unexplained weight loss of about 5 kg or more. Weight loss that occurs as a result of cancers is due to the release of cytokines from cells of the immune system. In end-stage cancer, this weight loss is known as  cachexia . Fever, which is also induced by cytokines, is often found in patients with advanced cancer, although this may also be an early warning of certain types of cancer. An example of this is Hodgkin’s lymphoma, which is characterized by fever, often during sleep, and is accompa...

  GENERAL TREATMENT OF CANCER The traditional treatment for primary tumors that have not metastasized to other locations in the body has been surgical excision of the tumor, followed by chemotherapy or radiation therapy (radiotherapy). Chemotherapy involves the use of drugs to kill cancer cells while radiotherapy uses ionizing radiation. However, where a tumor has been diagnosed in an advanced state with metastases in other parts of the body, palliative care only may be given, to ease pain and discomfort. ‘Staging’ of the cancer is essential as it determines the treatment that the patient receives. Staging of a cancer involves looking at the extent of the cancer within the body. Though staging varies between different types of tumor, a simple system classifies the tumor into one of four stages as shown in  Table 17.6 . Other staging systems include the TNM classification, where T records how far the primary tumor has grown in its original location, N defines whether the tumor ...

  CHEMOTHERAPY More than 100 different drugs are used to treat different cancers. They are usually given in combination and with radiation therapy and/or surgery. Most of the chemicals used in the treatment of cancer are, traditionally, those that kill cells, that is they are cytotoxic. Most are active on cells that are dividing, that is they are cycle-dependent. Drugs which kill cells that are not dividing are noncycle-dependent. There is also some evidence that at least some cytotoxic drugs act by inducing terminal differentiation or apoptosis in cancer cells. Many different types of chemicals target cell division in various ways. For example, several categories of drug interfere with DNA synthesis. These include folic acid antagonists, alkylating agents and purine and pyrimidine analogs and the topoisomerase inhibitors . Other drugs inhibit cell division by disrupting the polymerization or depolymerization of microtubules, thus interfering with the separation of chromosomes duri...