Cancer as a genetic disease

It is known that cancer is linked to harmful genetic alterations of cells and many genes have been linked to various forms of cancer, but the genetics of cancer is very complicated and less well understood than classic genetics. No single cancer-causing gene has ever been discovered that is mutated in all cancers, and even in specific tumour types there can be several possible genetic mechanisms and genes involved in the formation of the tumour. In some families an inherited disposition has...

Staging of malignant disease

To ensure that every patient can be advised about the most appropriate management of his or her particular disease, it is vital that the extent of the cancer is known, e.g. if a patient presents with a breast lump that proves to be malignant, it would be inappropriate to offer the patient a mastectomy if the cancer had already spread to the liver. Removal of the breast would not affect the patient's prognosis, because the cancer would already have metastasized at the time of diagnosis. This is...

Immune system in patients undergoing chemotherapy and radiotherapy

All the immune cells of our body (e.g. neutrophils, lymphocytes, monocytes, NK cells) are developed from stem cells in the bone marrow. In the bone marrow, there is about one stem cell for every 100000 blood cells. Neutrophils, which are the largest fraction of white blood cells, account for about 54-63 of all white blood cells and they are the first immune cells to arrive at the site of infection and the first line of defence against invading pathogens. Their numbers in circulation do not...

Lung cancer

Symptoms for this disease may not be experienced in the early stages of development and, when symptoms do occur, they are usually the result of the cancer growing and causing pressure or pain, e.g. a persistent cough, wheezing and shortness of breath and blood in the phlegm recurrent chest infections, chest, shoulder or back pain not related to coughing, a husky voice, unexplained weight loss or loss of appetite and unsteady walking or occasional memory lapses and pathological fractures (Cancer...

Innate natural nonspecific immune response

The innate immune response is present at birth and is mediated by a complex sequence of cellular and molecular events including phagocytosis, inflammation, complement activation and natural Table 7.1 Cells of the immune system Immune cells that can ingest and digest foreign antigens pathogens by the process of phagocytosis, e.g. macrophages, neutrophils Antigen-presenting cells Process and present antigens to T lymphocytes, e.g. dendritic cells, macrophages, B cells Kill tumour cells and some...

Some facts

The bacterium Escherichia coli has a single circular DNA molecule of 4.6 million base-pairs, making the total length of this single DNA molecule around 1.4 mm. In humans there are around 3 billion letters in the DNA code. In a single diploid cell, if fully extended, the DNA would have a length of almost 2 metres. If all the DNA of the roughly 100 trillion cells in the human body were unwrapped and placed end to end, it would reach the moon 6000 times Fortunately, DNA in the human cell is not...

Unethical research

Kennedy and Grubb (2000) suggest that the greatest incentive to regulate health-care research was awareness of the atrocities committed during World War II in the name of medical research. According to Evans and Evans (1996) 23 doctors were convicted at the Nuremberg trials. Their deeds included freezing subjects in an attempt to discover the most effective means of treating hypothermia deliberately infecting subjects with malaria with an aim of discovering suitable vaccines and inflicting and...

The immune system and cancer

The interrelationship of immune response, old age and high incidence of cancer In recent years several factors have been associated with the development of human cancers, including smoking, dietary factors, infectious agents (viruses and bacteria), chemicals, radiation and hereditary factors (see Chapter 2). The treatment of normal cells with these factors results in the mutation of a wide range of genes such as tumour suppressor genes or genes coding for growth factor, growth factor receptors,...

Adaptive acquired specific immune response

In many situations, the non-specific immune responses described above (e.g. phagocytosis, NK cell activation, inflammation), with which we are born and that occur in the first few hours of infection, may be sufficient to overcome the pathogens. If not, disease can ensue and the body may recover after the activation of adaptive immune responses against the invading pathogens (see Figure 7.1). There are two types of adaptive immune responses, namely antibody-mediated immune (AMI) responses and...

A diagnosis of cancer

Volumes are now written and spoken upon the effects of the mind on the body. Much of it is true. But I wish a little more was thought of the effect of the body on the mind Florence Nightingale (1859 - cited in Price, 1990, p. xii) Almost 150 years have passed since Florence Nightingale wrote these words. Cancer is a protracted illness, always raising uncertainty in the minds of those affected, and their families, as to whether the disease can be successfully treated. Historically, the...

The impact of research on patient care

The NHS Cancer Plan (DoH, 2000a) highlights the importance of research for the detection and treatment of cancer. In particular it highlights the importance of research into the genetic and cellular changes that lead to an individual developing cancer. The Plan states (DoH, 2000a, p. 91) 10.26 The genetic makeup of an individual may determine how effective a particular medicine is and the risk of adverse side effects. Research in this area, known as pharmacogenetics, is accelerating as a result...

Genetic screening of cancer

As cancer has a strong genetic basis, genetic screening should have potential applications for determining prognostic information. In classic monogenic (one-gene) familial genetic disorders such as Huntington's disease, screening of potentially affected family members can allow people to know what their chances are of developing a disease. Screening can also allow potential parents to know what the likelihood is of any future offspring developing the condition. Unfortunately in cancer studies...

The future role of tumour markers in disease management

Since 1997 there has been major funding by the National Cancer Institute (NCI) in the USA on research for new diagnostic, prognostic and predictive cancer markers. Funding is also provided for translating research techniques that have been used on cell lines or animal models into clinical use, to assist oncologists when selecting the correct treatment strategies. Completion of the first stage of the Human Genome Project has provided sequence data and has advanced to the next stage of confirming...

Rituxan antibody rituximab

Rituxan was the first monoclonal antibody that was approved by the US FDA for the treatment of cancer in 1997. Rituxan is a chimeric mAb (34 mouse protein and 66 human protein) and is directed against B-lymphocyte-restricted differentiation antigen CD20. It has been developed by transferring the entire Fab domain of mouse anti-CD20 antibody to the human IgG1 framework (Hainsworth, 2000). CD-20 antigen is expressed on the surface of more than 90 of B-cell non-Hodgkin's lymphomas (NHLs), on pre-B...

Radiolabelled mAbs as radioimmunoconjugate agents

The goal of radioimmunotherapy (RIT) is to deliver cytotoxic radiation from therapeutic radioisotopes to tumours using mAbs (similar to a guided missile) that bind to those cells expressing the target antigen (Hainsworth, 2000 Cheson, 2001). The success of RIT depends on several factors, including the choice of the target antigens, antibody molecules (guided missiles) and therapeutic radioisotopes (Juweid, 2002), e.g. ideally the target antigen should be tumour specific and expressed only on...

Where did it all begin

The story began 40 years ago in the 1960s. Researchers in Philadelphia were able to identify a common genetic mutation in patients with CML. Chromosome 22 had a 'bit' missing. This became known as the Philadelphia chromosome and was found in 95 of CML patients, and was the first time that a genetic abnormality had been linked to a specific cancer. It took a further 13 years to find the 'missing bit'. It had moved to chromosome 9. This phenomenon of moving from one chromosome to another is known...

Randomized controlled trials

The randomized controlled trial (RCT) is generally referred to as the gold standard of research and is often used to compare interventions. It is basically an experimental trial comparing two or more groups who are randomly allocated to either one form of treatment or another. It is through this random allocation that the risk of extraneous variables is reduced, thus increasing the chance that any changes are caused only by the intervention, so allowing the cause and effect to be determined....

Quasiexperiments casecontrol studies and cohort studies

A case-control study may be used to investigate a problem related to a cause of disease. Patients with a particular condition (cases) are compared with an identical group of individuals who do not have the condition (controls). Both groups should be identically matched except for the condition under study. Case-control studies are generally retrospective, and accounts of past history and exposure are investigated to ascertain the common lifetime exposures, linking these to possible causation of...

Angiogenesis

Angiogenesis is one example of laboratory research translated into clinical practice. It is the growth of a new blood supply from pre-existing vasculature. The existing capillaries sprout new branches to serve and nurture the tumour. This is triggered by proteins known as tumour angiogenesis factor and involves numerous biological activities (Tortora and Grabowski, 2003). Preclinical studies have demonstrated the major role of angiogen-esis, tumour growth and formation of metastases, which lead...

Imatinib mesylate

Another example of translational oncology research is one of the great successes of recent years, and this is the story of imatinib mesylate (Glivec) has dramatically changed the lives of patients with chronic myeloid leukaemia (CML). CML is a disease of the myeloid stem cell characterized by marked splenomegaly and an increase in the production of white cells. The natural course of CML is a chronic phase, as described above, moving into an accelerated or blast crisis that, untreated, leads to...

Phenomenology

During the past two decades there has been increasing interest in the use of phenomenological research published within the nursing literature however, varied interpretations of the original philosophical assumptions underpinning this approach have led to much criticism (Koch, 1995 Paley, 1997 Van der Zalm and Bergum, 2000). Phenomenology as described by Husserl (1859-1938) is the study of the 'lived experience' whereby the researcher aims to uncover or illuminate the real meaning of human...

Herceptin trastuzumab

Herceptin was the first therapeutic monoclonal antibody that was approved by the US FDA for the treatment of solid tumours in 1998 (Bell, 2002 Freebairn et al., 2001). Unlike Rituxan, Herceptin is a humanized antibody, which is directed against the external domain of the human epidermal growth factor receptor-2 (HER-2). It has been approved for the treatment of patients with metastatic breast cancer whose tumours overexpress HER-2 receptors. HER-2 is a non-mutated, tumour-associated, cell...

The immune surveillance theory

The immune surveillance theory put forward by Thomas in 1959 and redefined by Burnet (1967) states that the immune system is constantly patrolling the body for tumour (abnormal) cells, which are recognized as foreign, and mounts an immune response that results in their elimination before they become clinically detectable (Burnet, 1967). Although this concept remains controversial, a wide range of evidence supports it. First, cancer patients with tumours infiltrated by many immune cells (e.g....

Predisposing factors to developing cancer

As society becomes more affluent, so the incidence of cancer can be demonstrated to rise. There could be a number of explanations for this, including increased wealth and improved health care enabling individuals to achieve a greater life expectancy than their grandparents (Gabriel, 2001). People are also surviving previously life-threatening illnesses, such as infectious diseases, major accidents, etc., only to live longer and possibly to develop cancer later in life. We also know that more...