28 minute read
Palliative Surgery
from Issue 14
palliative Care is Common in treating terminally ill patients. one important aspeCt is treating CanCer patients with surgiCal interventions. suCh interventions for CanCer patients puts palliative Care at the forefront of ethiCal debates. this artiCle will explore some of the prinCiples of biomediCal ethiCs with respeCt to palliative interventions in patient Care.
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One possible route of palliative treatment available to cancer patients is surgery. However, the ethical implications of palliative surgical treatment are under continuous debate. Issues involved in the practice and research of palliative surgery will be explored using the four principles of biomedical ethics.
What is Palliative caRe?
According to the World Health Organization, “palliative care” Rohan Kehar quality of life in those patients with non-curable diseases (Cimino, 2002). Palliative care is common in treating terminally ill patients. Its purpose is to alleviate symptoms with minimal impact on the patient’s survival without worsening the patient’s condition. Techniques such as radiotherapy, chemotherapy, and surgery in addition to a support system are used to help the patient cope with the illness (Cimino, 2002).
PRinciPles of Biomedical ethics
Beauchamp and Childress provided the impetus to develop the four principles of biomedical ethics: beneficence, nonmaleficence, respect of autonomy, and justice (Hofman, 2005). Beneficence and nonmaleficence mean ‘doing good’ and ‘doing no harm’ on the part of the clinician. Both served as
the foundation for those traditional and paternalistic beliefs which maintains ‘doctor knows best’. Patient autonomy means that the patient has the right to informed consent and to input in decision-making (Hofman, 2005). ‘Justice’ is a principle that entitles each patient to an equal level of attention from clinicians. The application of these principles is important in understanding the ethical concerns of palliative surgery for differs from conventional medical care by promoting the
cancer patients.
ethical issues in Patient caRe
To discern the prevalent ethical concerns, McCahill et al. (2001) devised a 110-item survey. Its purpose was to determine the extent that palliative surgery was practiced and to identify ethical concerns involved in their decision making. The most frequent ethical dilemmas reported include: ‘providing honest information without destroying hope’, ‘uncertainty about the patient’s prognosis’, ‘preserving patient choice’, and ‘withholding/withdrawing life-sustaining treatments’ (McCahill, 2001). Patients are entitled to informed consent and full disclosure, but a balance must be achieved between informing the patient and maintaining hope. If a clinician reveals the truth, especially in a manner that is not sensitive to the patient’s state, the bad news may worsen the patient’s condition. On the other hand, it is unethical to withhold information that is pertinent to future treatment plans. In doing so, the clinician can influence the patient’s decision and compromise their autonomy. For example, if an oncologist believes major surgery is the best option for a patient with Stage IV breast cancer, it would be unethical according to the principle of autonomy to withhold information about alternative treatments such as chemotherapy or radiotherapy. Therefore, it is recommended in palliative care to make the patient aware of the severity of
the illness in a manner that gives the patient the opportunity to make decisions, while preserving their hope (Krouse, 2002). It is recommended that a paternalistic model be avoided. Information about treatment options should be made known to the patient, as the patient has the right to informed consent. However, uncertainty with the patient’s prognosis results in ambiguity, in which case, how much detail should be elucidated to the patient if doubt exists with respect to the prognosis? Concerns about the quality of life should take precedence over informed consent as physicians have a duty to do no harm to the patient. Preserving patient choice is an important principle to uphold, but its application should consider individual circumstances. One could argue that patients should be tested to ensure impaired thinking is not impacting the decision making process (Davies, 1995). Suggestions in the medical literature contend that patients should undergo mental health examinations to determine if they can make adequate choices (Krouse, 2002). If the patient is incapable of making decisions regarding one’s health, a substitute decision maker should be delegated. Otherwise, an incapacitated patient may decide to refuse promising treatment. Another issue is whether or not it is ethical to withhold a treatment, even if it is demanded by a patient. In their Code of Medical Ethics, the American Medical Association discusses this concept and claims that “physicians are not ethically obligated to deliver care that, in their best professional judgment, will not have a reasonable chance of benefitting their patients. Patients should not be given treatments simply because they demand them” (Davies, 1995). Thus, while the patient may demand surgery, the physician is entitled to refuse such a request. However, what if this lack of adherence negatively impacts the doctor-patient relationship? Some clinicians argue that questionable therapy is justified on the grounds of maintaining the trust and cooperation of the patient (Krouse, 2005). But refusing a patient’s request also conflicts with a physician’s ‘duty to help’ (Krouse, 2005). The physician may wish to help the patient and adhere to their requests, but this may lead to futile treatment.
ethical issues in clinical ReseaRch
Another ethical concern is the lack of reliable and valid scientific evidence in support of palliative surgical treatments. Many surgical cancer treatments have not been subjected to a randomized controlled trial (RCT), resulting in a possible placebo effect (Hofman, 2005). Although this is not necessarily a negative outcome when it comes to palliative care, it is still in the practice of good science to discern the effect of treatment from a given intervention. However, there is an insufficient number of RCTs because it is unethical to use placebos to randomize control patients in a surgical trial. Many operations that are medically futile, or even detrimental in terms of patient risk, continue to be employed, such as palliative nephrectomy for radiating pain (McCahill, 2001). According to Hofman et al. (2005) these widely accepted surgical procedures require ethical consideration. In context of Beauchamp’s and Childress’ principles of biomedical ethics, it is a physician’s duty to do no harm. Performing a procedure that is known to be detrimental is an unethical practice. There is a responsibility among clinicians to help individuals with non-curable disease such as cancer, and surgery provides an important option to palliate symptoms. But despite the desire to adhere to patient needs, if there is insufficient scientific evidence for a surgical option, alternative methods should prevail. Otherwise, a surgical option becomes unethical.
RefeRences
Cimino, J.E. (2002). A clinician’s understanding of ethics in palliative care: an American perspective. Critical Reviews in Oncology/
Hematology, 46, 17-24. Davies, B., Reimer, J.C., Brown, P., and Martens, N. (1995). Challenges of conducting research in palliative care. Omega, 31, 263-73. Hofman, B., Haheim, L.L., & Soreide, J.A. (2005). Ethics of palliative surgery in patients with cancer. British Journal of Surgery, 92, 802-819. Krouse, R.S. (2002). Palliative care for oncological patients. Journal of
American College of Surgeons, 198,311-319. McCahill, L.E., Krouse, R.S., Chu, D., Juarez, G., Uman, G.C., Ferrell,
B.R., &Wagman, L.D. (2001). Decision making in Palliative Surgery.
Journal of American College of Surgeons, 195, 411-423.
Paradigm Shift: Cancer Stem Cells
Kevin Wang
despite rapid teChnologiCal advanCements, CanCer remains to be one of the leading Causes of mortality. sinCe the introduCtion of Chemotherapy and radiation nearly half a Century ago, there has been little advanCement in CanCer treatment. the present artiCle will examine the CanCer stem Cell hypothesis, whiCh is proving to proliferation is prevented by restricting the stem cells’ ability be a promising model that may lead to novel therapy targets.
“We have to find something that walks like cancer, talks like cancer, but isn’t cancer.” “Cancer stem cells are real!”
Such were the words of Dr. Gregory House (from popular TV series, House) as he elucidated the presence of cancer stem cells. It has long been known that cancers originally develop from one or a few normal cells that acquire the ability to proliferate and metastasize. Yet, the origin of these tumours remains a mystery. Only recently has the discovery of cancer stem cells begin to shed light on the underlying mechanisms of oncogenesis. This potential paradigm shift in cancer biology may one day lead to the development of new treatment strategies that target the heart of a tumour by attacking the cells that initiate them.
PRoPeRties of stem cells
In order to understand the Cancer Stem Cell (CSC) hypothesis, we must first revisit the basics of stem cell biology. In the early stages of human life, a totipotent pool of cells differentiate into the germ layers, each of which further develop into tissue types in the body. The genesis of new cells occurs through a small pool of somatic stem cells that are responsible for the development and maintenance of tissues throughout one’s lifetime. These somatic stem cells have the capacity to selfrenew and differentiate into one or more mature cell types (Figure 1). Each division gives rise to two daughter cells, a stem cell and a progenitor cell. The stem cell renews the renew but acquires the ability to differentiate into mature cell types (Lobo et al., 2007). In normal tissues, these self-renewing stem cells can differentiate into progenitor and mature cells depending on their microenvironment (Bjerkvig et al., 2005). Unregulated
stem cell pool and the progenitor cell loses the power to selfto self-renew. Cancer stem cells have similar self-renewal and differentiation ability as stem cells, except its growth is unregulated.
evidence of canceR stem cells
The stochastic theory of oncogenesis fails in its inability to explain two important observations in cancer growth (Lobo et al., 2007). For decades, scientists have observed that most tumours arise from a single cell, but not all the cells within the
Figure 1 Normal stem cell differentiation to different lineages of nerve cells (NINDS, 2005).
tumour are identical, a concept known as tumour heterogeneity (Heppner, 1984). This diverse morphology cannot be explained by a somatic cell that has acquired the ability to proliferate as it cannot differentiate into different cell types. The CSC hypothesis, on the other hand, is able to explain this anomaly through the generation of a pool of progenitors, each of which, depending on its cellular niche, can differentiate into the desired cell type (Calvi et al., 2003). In many cancers, portions of the tumour are cancerous, while others are “normal” cells that support the growth of the tumour. The second observation stems from the observation that, despite the stochastic model suggesting that a single cell can generate a tumour, at times even large numbers of cancerous cells fail to do so (Lobo et al., 2007). If all the cells within a tumour have the same proliferative potential, one would assume that even a few cells can recapitulate the original tumour, yet this has not been demonstrated in the lab. The CSC hypothesis postulates the existence of a cellular hierarchy whereby only a small population of the tumour is capable of self-renewal and thus generating a new tumour. As the cancer stem cells proliferate, a large pool of progenitors is responsible for the bulk of the tumour, yet these cells only have a limited capacity to replicate and cannot initiate tumour formation de novo. Another observation stems from mutations that give rise to cancers. Despite rigorous regulatory mechanisms, mutations that result in aberrant proliferation during mitoses do occur. Many of the tissues in which malignancies originate are composed of short-lived cells such as skin, or blood. Many cancers require a specific series of mutations involving signal transduction, cellular control, and DNA repair mechanisms. These differentiated progenies are often protected from genotoxic stresses due to their relatively shorter life-span. Stem cells may be preferential targets of initial oncogenic mutations, as they are maintained throughout a person’s lifetime, thus have many opportunities to accumulate mutations (Lobo et al., 2007).
canceR stem cells in diffeRent tissues
Leukemia
The existence of stem cells began with the discovery of hematopoietic stem
Figure 2 Hypothesized cellular origins of cancer stem cells: a) stem cell, b) progenitor cell, c) differentiated cell (Bjerkvig et al., 2005)
cells by Till and McCulloch in 1961. They were able to demonstrate clones that could give rise to multilineage colonies consisting of different blood cells (Till & McCulloch, 1961). Fittingly, the first discovery of cancer stem cells also took place in hematology. John Dick’s group at the University of Toronto was the first to isolate a population of primitive hematopoeitic stem cells in acute myeloid leukemia (AML) in 1997 (Bonnet & Dick, 1997). This small population of tumour cells, characterized by surface markers CD34+CD38-, when transplanted into recipient mice, was able to recapitulate the phenotypic profile of the original cancer.
In order to substantiate the CSC theory, it became critical to isolate stem cell populations in other cancer types. To find CSCs in solid tumours became the Holy Grail in the field as the surface markers required to isolate CSCs were still unknown. In 2003, Michael Clarke’s lab succeeded in finding CSCs in breast tumours. In a mouse model, as few as 100 breast cancer stem cells (CD44+CD24-) injected into the breast of healthy mice formed tumours, whereas tens of thousands of other cancer cells isolated from the same original tumour were unable to do so (Al-Hajj et al., 2003; Dontu et al., 2003).
Brain Cancer
CSC in the central nervous system was another hard-sought trophy due to the long-held dogma that brain tissue becomes quiescent in adulthood. In 2004, Sheila Singh, formerly at the University of Toronto (now a scientist at the McMaster Stem Cell and Cancer Research Institute), identified similar stem-like cells in human brain tumors. These CSCs, composing a much smaller portion of the tumour were isolated using the marker CD133. In a mice xenotransplantation model, it was demonstrated CD133+ tumour cells were able to generate the original tumor even when 1000 fold increase in the CD133- population were unable to do so (Singh et al., 2004). Since this discovery, CSCs were identified in several other tissue malignancies including melanoma, bone, ovarian, prostate, and colon cancers (Fang et al., 2005; Gibbs et al., 2005; Bapat et al., 2005; Collins et al., 2005; O’Brien et al., 2007).
canceR stem cell Biology
Since the discovery of CSCs, one central question involves the cellular origin of these cells. As both CSCs and normal stem cells must renew themselves and induce differentiation, it is reasonable to assume some molecular mechanisms are shared. Even though researchers have been able to isolate CSCs from tumours, no one has been able to differentiate CSCs from their normal counterparts as they often share the same molecular markers (Lobo et al., 2007). It remains to be elucidated whether it is the progenitors which have accumulated mutations and now can revert back to a CSC, or whether it is the normal stem cell transforming into a CSC (Figure 2). Recent evidence is showing that both are possible; however, the molecular pathways that lead to these transformations remain to be discovered (Bjerkvig et al., 2005). Regulation of stem cell functions has become a rapidly growing research field. Studies published in 2003 by Molofsky and Sauvageaou independently demonstrated the role of polycomb-group protein, Bmi-1, as crucial in the self-renewal of CSCs (Molofsky et al., 2003; Lessard & Sauvageau, 2003). In patients with AML, expression of Bmi-1 is much higher than in normal bone marrow, indicating a potential relationship in causing oncogenesis. Another important pathway that is associated with many types of cancer is the Wnt/βcatenin pathway. Although crucial in normal development, they have been implicated in the self-renewal of CSCs (Reguart et al., 2005).
Figure 3 Current versus prospective therapy targets (Bjerkvig et al., 2005).
clinical and ethical consideRations
Despite the vast amount of resources invested into cancer research, the prospect of a cure has long eluded scientists. The CSC hypothesis may one day provide the answer to a cure. From a clinical point of view, it becomes necessary to target CSCs while not harming the normal stem cells that are vital to tissue growth and repair. Many current chemotherapies target the bulk of the tumour mass, which may explain the high likelihood of relapse. Current therapies operate under the assumption that all cancer cells have equal malignant potential. Thus, in many cases, a small population of cells remains after treatment. In fact, recent reports have shown
RefeRences
that CSCs are more resistant to conventional therapies, including chemotherapy (Costello et al., 2000) and radiation (Bao et al., 2006). Future treatment strategies must focus on targeting and eliminating the CSCs which drive the growth of the tumour (Figure 3). The study of cancer stem cells have come under much scrutiny due to the use of embryonic stem cells (cells obtained from aborted fetuses). In Canada, there is a relative freedom in scientists’ access to rare stem cell samples, but this is not the case for many other nations including the United States (however this is rapidly evolving under the new Obama administration). Despite the promising new findings, many barriers remain to be overcome before these advances
can be translated to patient care.
Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J., Clarke, M.F. (2003).
Prospective identification of tumorigenic breast cancer cells. Proc. Natl.
Acad. Sci. 100:3983–88. Bao, S., Wu, Q., McLendon, R.E., Hao, Y., Shi, Q., et al. (2006). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 444:756–60. Bapat SA, Mali AM, Koppikar CB, Kurrey NK. 2005. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res., 65:3025–29. Bjerkvig R, Tysnes BB, Aboody KS, Najbauer J & Terzis AJA. 2005. The origin of the cancer stem cell: current controversies and new insights. Nature
Reviews Cancer., 5: 899-904. Bonnet D, Dick JE. 1997. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med., 3:730–37. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, et al. 2003. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature, 425:841–46. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. 2005. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res., 65:10946–51. Costello RT, Mallet F, Gaugler B, Sainty D, Arnoulet C, et al. 2000. Human acute myeloid leukemia CD34+/CD38− progenitor cells have decreased sensitivity to chemotherapy and Fas-induced apoptosis, reduced immunogenicity, and impaired dendritic cell transformation capacities.
Cancer Res., 60:4403–11. Dontu G, Al-Hajj M, Abdallah WM, Clarke MF, Wicha MS. 2003. Stem cells in normal breast development and breast cancer. Cell Prolif., 36(Suppl. 1):59–72. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, et al. 2005. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res., 65:9328–37. Gibbs CP, Kukekov VG, Reith JD, Tchigrinova O, Suslov ON, et al. 2005. Stem-like cells in bone sarcomas: implications for tumorigenesis. Neoplasia ,7:967–76. Heppner GH. 1984. Tumor heterogeneity. Cancer Res., 44:2259–65. Lessard J, Sauvageau G. 2003. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature, 423:255–60. Lobo NA, Shimono Y, Qian D, Clarke MF. 2007. The Biology of Cancer Stem Cells.
Annual Review of Cell and Developmental Biology, 23:675-99. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. 2003. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature, 425:962–67. National Institute of Neurological Disorders and Stroke (NINDS) (2005). The
Life and Death of a Neuron. National Institutes of Health. Retrieved January 25, 2009, from http://www.ninds.nih.gov/disorders/brain_basics/ninds_ neuron.htm O’Brien CA, Pollett A, Gallinger S, Dick JE. 2007. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 445:106–10. Pardal R, Clarke MF, Morrison SJ. 2003. Applying the principles of stem-cell biology to cancer. Nat. Rev. Cancer, 3:895–902. Reguart N, He B, Taron M, You L, Jablons DM, Rosell R. 2005. The role of Wnt signaling in cancer and stem cells. Fut. Oncol., 1:787–97. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, et al. 2004. Identification of human brain tumour initiating cells. Nature, 432:396–401. Till JE, McCulloch CE. 1961. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res., 14:213–22.
Stress in the Lives of Cancer Patients
Current advanCements in CanCer therapy are quiCk to Capture the attention of soCiety. however, with no real Cure, patients must struggle to live with the effeCts of CanCer - beyond its biologiCal ConsequenCes. this artiCle introduCes some of these faCtors and the stresses that patients faCe. Crystal Chung
Becoming ill with cancer is a frightening thought. Amidst the brouhaha of emerging cancer therapies and endless risk factors, other implications of cancer are often unnoticed. Most understand that it can be devastating, but never truly recognize the depth at which this disease affects its patients. Not only does it have severe biological consequences in a human host, there are several other dimensions in which cancer can affect quality of life. While some factors are consistently found with each cancer, others define the specific characteristics of the disease. By looking at the psychological, physical, and familial implications of one specific cancer, such as breast cancer, we can begin to form a comprehensive understanding of the hardships that cancer patients face beyond their biological struggles. Breast cancer is the most common cancer among women worldwide, apart from non-melanoma skin cancers (World Health Organization, 2004). According to the Canadian Cancer Society, one in nine Canadian women will develop some form of breast cancer in her lifetime. What follows is an overview of breast cancer literature on select issues pertaining to the lesser known effects of this prevalent disease.
Psychological imPlications
A study in London, England, continually interviewed 170 women with early staged breast cancer for five years after initial diagnosis. It was found that, within the five year period, 60% of women reported episodes of anxiety and/ or depression (Burgess et al., 2005). It is not difficult to understand why these women experience feelings of distress. Apart from the obvious health concerns, there are difficult decisions that need to be made about treatment options and uncertainties regarding the future.
Unfortunately, this stress can exacerbate or be the result of pain and fatigue; these are the two most prevalent symptoms in cancer patients (Kurtz et al., 2008). Not only can these interfere with the patient’s daily activities and motivation to exercise – a very important part of the healing process (Holmes et al., 2005) – but it can lead to catastrophizing. Catastrophizing is exhibited when patients display negative thoughts about themselves or the future, and do not possess a “fighting spirit” (Jacobson et al, 2004). In general, there is a strong association between depression and fatigue in breast cancer patients (Reuter et al., 2006) which can have a broad effect on many aspects of their lives during recovery. Given these psychological effects after cancer diagnosis, research on coping mechanisms and social support has become increasingly important. In general, those who cope best with stress after diagnosis demonstrate higher psychological and physical quality of life throughout their treatment and recovery (Golden-Kreutz et al., 2005). The quality of life scores were assigned using the Medical Outcomes Study-Short Form (SF-36), a questionnaire
that evaluates several categories, including physical and mental health, pain, and health perception (Ware et al., 1993). Additionally, women with more significant social support systems have lower mortality rates in some studies (Kroenke et al., 2006). These networks, formed by a collection of family, friends, and confidants, serve as an important avenue for emotional release. Therefore, it may be necessary to address the social and psychological issues facing patients throughout the course of recovery.
Physical effects
The physical appearance of cancer patients can change dramatically over the course of illness. Hair loss is a side effect of some chemotherapy regimes. Since, traditionally, hair was sometimes viewed as a symbol of culture or identity, many patients lose their self-confidence (Münstedt et al., 1997). However, nowadays, the effect of hair-loss depends on the patient’s disposition: while one person may see hair-loss as a representation of their disease progression, others see it as a sign of pride and bravery (Batchelor, 2001). Women with breast cancer face another body image problem that can especially affect their sexuality. Women report less satisfaction with themselves, due to factors such as weight gain, breast surgeries, hair loss, and problems with sexual activity. The latter issue is compounded if they feel that their partners do not understand the sexual implications of the disease (Fobair et al., 2006). Mastectomies (removal of the breast) and lumpectomies (removal of an isolated part of the breast) adds another dimension of fear and anxiety about rejection from a partner or suppressed self image. In one study, 41% of mastectomy patients felt uncomfortable and unhappy with their bodies six months after surgery. Of lumpectomy patients, 8% felt a similar way. In general, perceived body image after breast surgery becomes less of a problem over time (Schain et al., 2006). However, it plays a large part in treatment decisions as the outcome is often irreversible, except in the case of breast reconstruction. Yet, even with reconstruction, relationships may not revert back to their original charm since some become fearful of hurting their partners or reopening scars when intimate (Sandham & Harcourt, 2006).
familial conceRns
While there are considerable personal issues to face during cancer recovery, many patients often think of the disease implications on their loved ones. Due to the nature of genetics, some cancers have a familial component, which naturally places relatives at an elevated risk compared to the general population. For example, the risk of breast cancer in women increases as the number of first-degree relatives with breast cancer increases (Collaborative Group on Hormonal Factors in Breast Cancer, 2001). The familial links between patients with breast cancer has spurred much research into mutated genes that may predispose cancer. The BRCA1 and BRCA2 genes have been heavily studied within populations of people with breast and ovarian cancer. In one study, it was found that approximately 25% of patients who were identified within families at risk of breast cancer carry a mutation in either gene (Shih et al., 2002; Simard et al., 2007). However, the actual population prevalence of mutations in the BRCA1 and BRCA2 genes is low within those affected by breast cancer (Risch et al., 2001). Given the more sensitive methods of detecting genetic mutations and earlier detection of cancer risks, women are becoming more stressed with genetic consultation. Patients and professionals feel that at the time of diagnosis, cancer patients would rather avoid the extra anticipation of genetic testing unless it played a role in altering treatment decisions (Ardern-Jones, 2005). Additionally, the joint occurrence of cancer diagnosis and positive cancer gene screening can result in perceived urgency from the patient, thereby giving them less time for rationalization of treatment options. This can lead to major changes, as in the case of mastectomies, and overtreatment (Ardern-Jones, 2005). The impact of genetic testing becomes even more important as studies have found an increase in post-traumatic stress disorder in mutated BRCA1/2 carriers when compared to those who do not have the mutation (Hamann et al., 2005).
closing RemaRks
While the example of breast cancer has been used to explore some of the difficulties that patients face, it is important to keep in mind that many of these hardships are applicable to patients with other types of cancer. The variety of stresses experienced by patients is by no means limited to the factors introduced here. One must also be cognizant of specific complications arising from different therapies, the effect on one’s career, as well as the implications for those who consider having children. Financial burden can be disheartening, while religious obligations may also add pressure to the patient. By understanding the multifaceted effects of cancer, support networks and health providers can better assist patients with their struggles. In realizing that cancer therapy is not just a battle against rogue cells, society can play a role in helping to maintain quality of life and happiness in the infirm. .
RefeRences
Ardern-Jones, A., Kenen, R., Eeles, R. (2005). Too much, too soon? Patients and health professionals’ views concerning the impact of genetic testing at the time of breast cancer diagnosis in women under the age of 40. European
Journal of Cancer Care. 14(3):272-281. Batchelor, D. (2001). Hair and cancer chemotherapy: Consequences and nursing care—A literature study. European Journal of Cancer Care. 10:147–163. Burgess, C., Cornelius, V., Love, S., Graham, J., Richards, M., Ramirez, A. (2005).
Depression and anxiety in women with early breast cancer: five year observational cohort study. British Medical Journal. 330:702. Canadian Cancer Society/National Cancer Institute of Canada: Canadian Cancer
Statistics 2008, Toronto, Canada, 2008. Collaborative Group on Hormonal Factors in Breast Cancer. (2001). Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986 women without the disease. The Lancet. 358(9291):1389-1399. Fann, Jesse, Thomas-Rich, A., Katon, W.,Cowley, D., Pepping, M., McGregor,
B., Gralow, J. (2007). Major depression after breast cancer: a review of epidemiology and treatment. General Hospital Psychiatry. 30(2): 112-126. Fobair, P. Stewart, S., Chang, S., D’Onofrio, C., Banks, P., Bloom, J. (2006). Body image and sexual problems in young women with breast cancer. Psycho-
Oncology. 15:579-594. Golden-Kreutz, D., Thornton, L., Wells-Di Gregorio, S., Frierson, G., Jim, H.,
Carpenter, K., Shelby, R., Andersen, B. (2005). Traumatic Stress, Perceived
Global Stress, and Life Events: Prospectively Predicting Quality of Life in
Breast Cancer Patients. Health Psychology. 24(3):288-296. Hamann, H., Somers, T., Smith, A., Inslicht, S., Baum, A. (2005). Posttraumatic
Stress Associated With Cancer History and BRCA1/2 Genetic Testing.
Psychosomatic Medicine. 67:766-772. Holmes, M., Chen, W., Feskanich, D., Kroenke, Colditz, G. (2005). Physical Activity and Survival After Breast Cancer Diagnosis. Obstetrical & Gynecological
Survey. 60(12): 798-800. Jacobsen P., Andykowski, M., Thors, C. (2004). Catastrophizing among women receiving treatment for breast cancer. Journal of Consulting and Clinical
Psychology. 72(2): 355–361. Münstedt, K., Manthey, N., Sachsse, S., Vahrson, H., (1997). Changes in selfconcept and body image during alopecia induced cancer chemotherapy.
Support Care Cancer. 5:139–143. Reuter, K., Classen, C., Roscoe, J., Morrow, G., Kirshner, J., Rosenbluth, R., Flynn,
P., Shedlock, K., Spiegel, D. (2006). Association of coping style, pain, age, and depression with fatigue in women with primary breast cancer. Psycho-
Oncology. 15:722-779. Risch, H., McLaughlin, J., Cole, D., Rosen, B., Bradley, L., Kwan, E., Jack, E.,
Vesprini, D., Kuperstein, G., Abrahamson, J., Fan, I., Wong, B., Narod, S. (2001).
Prevalence and Penetrance of Germline BRCA1 and BRCA2 Mutations in a Population Series of 649 Women with Ovarian Cancer. The American
Society of Human Genetics. 68(3):700-710. Sandham, C. & Harcourt, D. (2006) Partner experiences of breast reconstruction post mastectomy. European Journal of Oncology Nursing. 11(1):66-73. Schain, W., d’Angelo, T., Dunn, M., Lichter, A., Pierce, L. (2006). Mastectomy versus conservative surgery and radiation therapy. Psychosocial consequences.
Psycho-Oncology. 73(4):1221-1228. Shih, H., Couch, F., Nathanson, K., Blackwood, A., Rebbeck, T., Armstrong, K.,
Calzone, K., Stopfer, J., Seal, S., Stratton, M., Weber, B. BRCA1 and BRCA2
Mutation Frequency in Women Evaluated in a Breast Cancer Risk Evaluation
Clinic. Journal of Clinical Oncology. 20(4):994-999. Simard, J., Dumont, M., Moisan, A., Gaborieau, V., Vézine, H., Durocher, F., et al. (2006). Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer. Journal of Medical
Genetics. 44:107-121. Ware, J., Snow, M., Kosinski, B., (1993). SF-36 Health Survey: Manual and interpretation guide. Lincoln, RI: Quality Metric Incorporated. World Health Organization Department of Measurement and Health
Information. (2004). Mortality and Health Status: Causes of Death. Geneva:
World Health Organization.
Cancer and Nanotechnology
Michael Chan & Stephanie Dreckmann
nanoteChnology is a rapidly growing field in biomediCal researCh
with promising impliCations in the development of novel methods to target CanCerous Cells. with a diverse repertoire of potential funCtions – from prophylaCtiC imaging to drug delivery – suCh nano-sized agents are Currently the subjeCt of muCh investigation. the following artiCle explores the properties of various nanoveCtor deviCes, the meChanisms through whiCh they eliCit their effeCts, as well as reCent findings from both in vitro and in vivo studies.
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O O O Core
End Groups
Figure 1 Generation 4 poly(benzyl) ether dendrimer consisting of OH core and end groups (Hawker, 1990). T he past few decades have seen great progress in basic cancer biology research; however, this progress has failed to translate into comparable advancements in clinical applications. One challenge accounting for this discrepancy involves the difficulty to develop agents that can evade biological barriers, and selectively target malignant cells with minimal side effects (Duncan, 1998; Ferrari, 2005). The emerging field of nanotechnology is a promising solution to this challenge. Nanotechnology is a multidisciplinary field involving the use of exceptionally small devices – at the scale of 1-100 nm – for selective delivery of drugs and imaging agents to cancer cells. This paper will discuss several of these nanotechnology
OH platforms including nanovectors and nanoshells.
nanovectoRs
Nanovectors are multifunctional devices usually comprising three components: (1) a core material, (2) a therapeutic or imaging agent, and (3) biological surface modifiers with or without a targeting group. The core material, which is usually made of biodegradable polymers, may carry one or more therapeutic agents. Biological surface modifiers are designed to increase the half-life of drugs in the body, protect drugs against enzymatic degradation, as well as avoid other obstacles. For example, polyethylene glycol (PEG) is a biological surface modifier that has been shown to prevent uptake of nanovectors by macrophages or other cells of the reticulo-endothelial system. In addition, nanovectors are designed to selectively deliver therapeutic
