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At least 469 records · Page 26Linked to original sources
PubMed2001

Oxidative stress in chemoprevention trials.

Prostate cancer continues to be the most frequently diagnosed cancer in men in the United States. Despite aggressive intervention, a significant number of men with prostate cancer will not be cured of their disease and will face the possibility of metastatic disease. Thus, development of potent prevention strategies to diminish or eliminate this threat is in order. Cellular exposure to chronic oxidative stress may be 1 possible etiologic factor in the development of many cancers, including prostate cancer. Oxygen radicals can attack DNA directly and result in the accumulation of potentially promutagenic oxidized DNA bases such as 8-hydroxydeoxyguanosine. In addition, chronic oxidant stress may also result in lipid peroxidation and the subsequent generation of a range of reactive products that can damage DNA. Disruption of certain genes may result in cellular tolerance to oxidative genomic injury. GSTP1 is an enzyme that helps catalyze the conjugation reaction between potentially damaging electrophiles and glutathione. Inactivation of GSTP1 has been documented to occur in nearly 100% of human prostate cancers; it is also frequently inactivated in prostatic intraepithelial neoplasia lesions. This inactivation may leave the cell vulnerable to oxidative DNA damage and/or tolerant to accumulation of oxidized DNA base adducts. These base adducts can be measured by several quantitative methods, such as gas chromatography-mass spectrometry with selected ion monitoring. These sophisticated methods can be readily integrated into prostate cancer chemoprevention studies of new and developing prevention agents by providing quantitative assessment of oxidative DNA damage before and after administration of these candidate chemopreventive drugs. The combination of genetic information, state-of-the-art assessment tools, and novel agents will allow rational, directed prostate cancer chemoprevention studies to be performed and, together, will help determine the role of chronic oxidative stress in the carcinogenic process of prostate cancer.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

[Current views in geriatric oncology].

Geriatric oncology represents a novel specialty which can be defined as specific older cancer patients management. It includes a validated geriatric procedure, the comprehensive geriatric assessment, which is the best way of approaching the complex interacting medical problems of frail older patients. Geriatric assessment of elderly cancer patients is actually a subject for discussion among geriatric oncology community. Geriatric assessment may provide either guidelines for anti-cancer treatment in the elderly, or guidelines for the management of older patients with cancer. Two clinical research ways are now developed : firstly the definition of the most relevant geriatric variables allowing clinical trials in such a heterogeneous population; secondly, the determination and the validation of a specific tool to screen frail and vulnerable older patients, and the study of the geriatric assessment impact on the quality of life of older cancer people.

Aged↗
PubMed2006

Elevation of thyroid cancer risk among cutaneous melanoma survivors.

Recent molecular studies have identified recurrent BRAF mutations in both cutaneous melanoma and thyroid malignancies. This relatively selective shared genetic vulnerability raises the possibility that these 2 tumors are connected through a common undisclosed pathogenic mechanism. To assess for possible associations between these 2 genetically related tumors at the population level, we calculated standardized incidence ratios (SIRs) for thyroid cancer (TC) among cutaneous melanoma (CM) survivors and CM among TC survivors using the National Cancer Institute's Surveillance, Epidemiology and End Result (SEER) database. Between 1973 and 2000, there were 73,274 and 27,138 cases of CM and TC cases, respectively. Overall, we found a 2.17-fold increase (p < 0.0000001) in the risk of TC after a diagnosis of CM. This augmented risk of TC is somewhat higher for males, for those diagnosed more recently and for the first 3 years after the CM diagnosis. We also detected a considerably smaller and borderline significant increased risk of CM (25%, p = 0.063) among the post-TC survivors. Of note, TC patients who received radiation therapy had a 57% increased risk of a subsequent CM (p = 0.034). Our study documents a strong unilateral risk of TC after CM. More studies are clearly needed to better delineate this mechanism.

Adult↗
PubMed1995

Actinic damage and skin cancer in albinos in northern Tanzania: findings in 164 patients enrolled in an outreach skin care program.

Persons with albinism are particularly vulnerable to the deleterious effects of UV light on their skin. We obtained histories and performed skin examinations on 164 albino patients living in equatorial Africa to determine their sun exposure, sun protection, and sun damage. Many patients did not wear hats and most wore short-sleeved shirts. Except for four infants, all patients had sunburned skin. Actinic cheilitis, actinic keratoses, and skin cancers were detected in many patients. Sun protection methods will be important for prevention of skin damage in albino patients.

Adolescent↗
PubMed1998

Epidemiology of occupational and environmental risk factors related to ovarian cancer.

This paper reviews articles published during 1970-1997 from 48 epidemiologic studies on occupational and environmental risk factors of ovarian cancer. Current evidence is characterized by poorly focused data for occupational and environmental agents, vulnerability to biases, and an almost complete lack of quantitative exposure-response data. The moderate amount of data on nurses, teachers, professionals, dry cleaning employees, women in agriculture, the pharmaceutical industry, pharmacists, waitresses, and cooks show very little, if any, evidence of excess risk. Hairdressers, beauticians, and women employed in the printing industry may be at increased risk, but the data are insufficient for strong conclusions. Some case-referent studies suggest a modest-to-moderate excess in association with genital talc application. Few high-quality studies have been carried out, and no chemical agents have been studied extensively, with the exception of exposure to talc. Ovarian cancer may have occupational and environmental etiologies intertwined with cultural, behavioral, and life-style factors and genetic susceptibility, but current knowledge is insufficient to quantify occupational and environmental etiologies reliably. Well-designed analytic epidemiologic studies with sufficient power are needed.

Adolescent↗
PubMed2005

A model for care across the cancer continuum.

With contemporary therapy, the majority of children and adolescents who are diagnosed with cancer will be cured. However, curative therapy predisposes to adverse health outcomes that affect the long-term survivor's quality of life and increase the risk of early mortality. Recognition of the adverse effects of cancer treatment on growth and development, vital organ function, fertility and reproduction, and secondary carcinogenesis has been the stimulus for the development of risk-adapted treatment approaches for pediatric malignancies. Because the consequences of these therapeutic modifications may not manifest for many years, long-term follow-up is required to accurately define new or changing patterns of adverse health outcomes, appropriate screening approaches, and ultimately, risk-reducing interventions. Identification of vulnerable survivors is essential to provide timely interventions to detect, ameliorate, reduce, or prevent cancer-related sequelae. This process is challenging, because risk factors constantly are evolving as cancer therapies are modified and as survivors age. Aging also disrupts the continuity of after-cancer care, as adolescent and young adult survivors graduate from pediatric oncology practices to community medical providers who are largely unfamiliar with cancer-related health risks. Health outcomes research objectives that target cancer survivors must adapt as cancer therapies evolve and as new risk factors for cancer-related morbidity emerge. Prospectively using a multidimensional, comprehensive approach that considers host-related, cancer-related, genetic, and lifestyle factors in combination with results from focused medical and behavioral evaluations obtained from cancer survivors who participate in long-term follow-up programs provides an optimal method of defining high-risk profiles for adverse health outcomes across the age spectrum.

Adolescent↗
PubMed2003

Psychological impact of colorectal cancer screening.

This article examines the psychological impact of participating in sigmoidoscopy screening for colorectal cancer prevention. The 1st study examined psychological well-being at 3 months, in relation to screening outcome, in 4,153 individuals. The 2nd study used longitudinal data to examine changes in psychological functioning from before to after screening in relation both to screening outcome and baseline indicators of vulnerability. There were few psychological differences between those who had received negative results or had polyps detected. These findings were confirmed in the longitudinal study, which also found no evidence for vulnerability to adverse effects among those who were initially most anxious or who perceived their risk of cancer to be higher. The longitudinal data suggested that screening might produce transient positive effects.

Anxiety↗
PubMed2004

Current and future use of hematopoietic growth factors in cancer medicine.

Myelosuppression, in particular neutropenia and anemia are serious complications of malignancy and its treatment. Neutropenia can make patients vulnerable to potentially life-threatening infection. It often results in dose reductions and delay of planned chemotherapy, which can have a significant detrimental effect on tumour response and survival. Anemia can be associated with a range of debilitating effects, which can severely impair patients' QOL. In addition, there is some evidence recognizing anemia as a poor prognostic indicator, associated with reduced treatment efficacy. Reduction in the duration and severity of neutropenia and anemia is possible by initiation of appropriate growth factors during the first and subsequent cycles of chemotherapy. New and improved growth factor support with agents such as pegfilgrastim and darbepoetin alfa has the potential to improve the management of chemotherapy-induced neutropenia and anemia further. Thrombopoietin is currently in clinical trials to assess its potential role in the treatment of thrombocytopenia in patients with cancer.

Anemia↗
PubMed2002

Arginine catabolism, liver extracts and cancer.

Although it is self evident that cells will not grow in amino acid deficient medium, an observation less well appreciated is that malignant cells are particularly vulnerable to such deprivation, which can lead to their rapid demise. Indeed, the more flagrantly malignant the phenotype (anaplastic the tumor), the more susceptible the cells seem to be to deprivation. While some attempts to employ this strategy in cancer treatment have been made, the difference between normal and malignant cells should be more fully exploited as a means of selectively eliminating tumor cell populations. To be successful, information on differences between the normal and the deranged cell cycle engine and checkpoints, especially how these are affected by deprivation, is of crucial importance. Since it is only recently that the controls at restriction points have been elucidated, it is little surprise that earlier attempts to control tumor cell growth by limiting the availability of an essential amino acid have met with limited success. Studies have been sporadic and isolated, often with little more than anecdotal descriptions as far as clinical work was concerned. This review concentrates on what has been accomplished primarily in vitro and since about 1950 with regard to arginine catabolism, while recognising that other essential amino acids have also been the focus of attention by some investigators. Treatments have included medium and plasma manipulation, dietary control, enzymatic degradation, and the use of liver extracts. On some occasions, substitution of amino acid analogues has been explored. It is argued that current knowledge, combined with past experience, calls for a much closer examination of the full potential of amino acid (and specifically arginine) deprivation as a means of controlling tumor growth, with greater attention to protocols that might be used to treat human cancers.

Animals↗
PubMed2000

Up-regulation of telomerase activity in human pancreatic cancer cells after exposure to etoposide.

Telomerase plays a critical role in the development of cellular immortality and oncogenesis. Activation of telomerase occurs in a majority of human malignant tumours, and the relation between telomerase and vulnerability to drug-mediated apoptosis remains unclear. In this study, we demonstrate, for the first time, up-regulation of telomerase activity in human pancreatic cancer cells treated with etoposide, a topoisomerase II inhibitor. Exposure of MIA PaCa-2 cells to etoposide at various concentrations (1-30 microM) resulted in two- to threefold increases in telomerase activity. Up-regulation was detectable 24 h after drug exposure and was accompanied by enhanced expression of mRNA of the human telomerase reverse transcriptase. Telomerase activation was also observed in AsPC-1 and PANC-1 cells but not in KP-3 and KP-1N cells. Furthermore, we found a negative correlation between increased telomerase activity and the percentage of dead cells after etoposide treatment. These findings suggest the existence of an anti-apoptotic pathway through which telomerase is up-regulated in response to DNA damage. This telomerase activation pathway may be one of the mechanisms responsible for the development of etoposide resistance in certain pancreatic cancer cells.

Antineoplastic Agents, Phytogenic↗
PubMed2004

[Complex forms of immune insufficiency to some cytokines (TNF-alpha, interferons) in colorectal cancers as exemplified by the COLO 205 cell line. Mechanism of resistance with special reference to signaling proteins and cytokines].

Since colorectal cancer cells are characterized by both high immune- and multidrug-resistance, investigations concerning the search for cytokines, especially interferons, which would delete cancer cells have prospects of success only if cancer cells became sensitive to such treatment. The prerequisite for successful treatment is to discover how the immune system kills colorectal cancer cells. In this article we focus our attention on signal transduction pathways in colorectal cancer cells, which are characterized by a variety of mechanisms that enable them to survive the hostile microenvironment created by immune system attack. Knowledge relevant to cancer cell immunity to defense mechanisms is crucial for the prospects of cytokine-supportet therapy. A case in point is the human colorectal cancer cell line COLO 205, which is not affected by individual cytokines, although it becomes vulnerable to combined treatment with some of them. It is not clear what factors make COLO 205 cells resistant to cytotoxins, however; it seems plausible to point to the complex signaling pathways, and STAT proteins in particular. Another feature of COLO 205 cells avoiding cytokine-mediated death signals is the reverse signaling causing activated macrophages to become dormant in response to soluble TNF-alpha receptors (sTNF-alpha R1, sTNF-alpha R2). Similarly, COLO 205 cells respond to the proinflammatory cytokine IL-6 released by activated macrophages. Cancer cells release anti-inflammatory cytokine IL-10, which ceases the action of PMNCs. It should be stressed that STATs mediate and/or activate the transcription of several genes indispensable for cell death. Cancer cells isolated from large bowel tumors express elevated constitutive activity of STATs inhibitors leading to antiapoptosis. Correspondingly, the increased survival rates of these cells could be attributed to accelerated actions of the PI-3K/Akt, cPKC/Raf1/ERK, NF- kappaB/JNK, or Jak/STAT cascades. Finally, an uncertainty in large bowel cancer cells is whether STATs might redirect the cytokine signal from cell deletion to cell survival.

Animals↗
PubMed2006

From vulnerable plaque to vulnerable patient--Part III: Executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report.

Screening for early-stage asymptomatic cancers (eg, cancers of breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (eg, heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government- or healthcare-sponsored reimbursement for atherosclerosis screening. Part I and Part II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the "vulnerable patient." These landmark discoveries, along with new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and treatment of the vulnerable patient are the focuses of this consensus statement. In this report, the Screening for Heart Attack Prevention and Education (SHAPE) Task Force presents a new practice guideline for cardiovascular screening in the asymptomatic at-risk population. In summary, the SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45-75 years of age and asymptomatic women 55-75 years of age (except those defined as very low risk) to detect and treat those with subclinical atherosclerosis. A variety of screening tests are available, and the cost-effectiveness of their use in a comprehensive strategy must be validated. Some of these screening tests, such as measurement of coronary artery calcification by computed tomography scanning and carotid artery intima-media thickness and plaque by ultrasonography, have been available longer than others and are capable of providing direct evidence for the presence and extent of atherosclerosis. Both of these imaging methods provide prognostic information of proven value regarding the future risk of heart attack and stroke. Careful and responsible implementation of these tests as part of a comprehensive risk assessment and reduction approach is warranted and outlined by this report. Other tests for the detection of atherosclerosis and abnormal arterial structure and function, such as magnetic resonance imaging of the great arteries, studies of small and large artery stiffness, and assessment of systemic endothelial dysfunction, are emerging and must be further validated. The screening results (severity of subclinical arterial disease) combined with risk factor assessment are used for risk stratification to identify the vulnerable patient and initiate appropriate therapy. The higher the risk, the more vulnerable an individual is to a near-term adverse event. Because <10% of the population who test positive for atherosclerosis will experience a near-term event, additional risk stratification based on reliable markers of disease activity is needed and is expected to further focus the search for the vulnerable patient in the future. All individuals with asymptomatic atherosclerosis should be counseled and treated to prevent progression to overt clinical disease. The aggressiveness of the treatment should be proportional to the level of risk. Individuals with no evidence of subclinical disease may be reassured of the low risk of a future near-term event, yet encouraged to adhere to a healthy lifestyle and maintain appropriate risk factor levels. Early heart attack care education is urged for all individuals with a positive test for atherosclerosis. The SHAPE Task Force reinforces existing guidelines for the screening and treatment of risk factors in younger populations. Cardiovascular healthcare professionals and policymakers are urged to adopt the SHAPE proposal and its attendant cost-effectiveness as a new strategy to contain the epidemic of atherosclerotic cardiovascular disease and the rising cost of therapies associated with this epidemic.

Coronary Artery Disease↗
PubMedDate not supplied

Cancer risk from low-level ionizing radiation: the role of age at exposure.

This article examines methodological issues related to epidemiologic investigations of the influence of age at exposure on radiation risk estimates; the epidemiologic literature on the role of age at exposure in radiation-cancer associations; and biological mechanisms that may account for associations observed in these studies. There is substantial evidence that young children, and especially the fetus, are highly vulnerable to ionizing radiation. Investigations also suggest that sensitivity may increase at the oldest ages of exposure. Further attention to modifying factors in radiation-cancer associations, such as age at exposure, may help to protect workers and the public by improving our understanding of sensitivity variation within populations.

Age Factors↗
PubMed2006

Ethical decision making on truth telling in terminal cancer: medical students' choices between patient autonomy and family paternalism.

INTRODUCTION: The effect of medical education is often hard to evaluate. We tried to assess whether a 2-hour, small-group discussion could alter student perspectives on truth telling. Currently, in Taiwan it is common practice to consult with the family of a terminally ill patient before telling the truth to the patient, which may be in conflict with patient autonomy. METHODS: The study was based on content analysis of self-reflective written texts after a 2-hour group discussion on a clinical case describing a truth-telling situation. The changes in decision patterns regarding the emphasis placed on patient autonomy versus family paternalism and the connection to related moral reasoning were subjected to focus analysis. RESULTS: The students' initial attitudes regarding the subject of truth telling were categorised into 4 patterns, namely, patient-centred (n = 46), family-centred (n = 20), simultaneous informing (n = 1), and situational informing (n = 5) modes. The discussion stimulated perspective changes in many of the students and their attitudes were then regrouped as patient-comprehensive (n = 35), family-centred (n = 1), and family-comprehensive (n = 36) modes. It was found that variations on 'common sense' and moral reasoning existed prior to the class and the students initially tended to overlook the complexity of truth telling in terminal cancer. Through the discussion and reflective learning, they were enabled to acknowledge the vulnerability of both the patient and his or her family, and to make decisions based on more comprehensive considerations. CONCLUSION: Group discussion seemed to be able to enhance ethical consideration. Further research is required to determine whether the benefits of this approach can be translated into behavioural changes in practice.

Attitude of Health Personnel↗
PubMed2005

[Evolutionary medicine: an emergent basic science].

Evolutionary Medicine is an emergent basic science that offers new and varied perspectives to the comprehension of human health. The application of classic evolutionary theories (descent with modification, and natural selection) to the human organism, to its pathogens, and their mutual co-evolution, provides new explanations about why we get sick, how we can prevent this, and how we can heal. Medicine has focused mainly on the proximate or immediate causes of diseases and the treatment of symptoms, and very little on its evolutionary or mediate causes. For instance, the present human genome and phenotypes are essentially paleolithic ones: they are not adapted to modern life style, thus favoring the so-called diseases of civilization (ie: ateroesclerosis, senescence, myopia, phobias, panic attacks, stress, reproductive cancers). With the evolutionary approach, post-modern medicine is detecting better the vulnerabilities, restrictions, biases, adaptations and maladaptations of human body, its actual diseases, and its preventions.

Biological Evolution↗
PubMed1989

Ethical issues in caring for the patient with advanced cancer.

The patient in the advanced stages of cancer presents many challenges for the nurse caregiver. To care for the patient effectively as the end of life approaches requires a shift in focus from cure or treatment of the disease to the management of the associated symptoms. This is the primary goal of palliative care, a unique approach to meeting the needs of this vulnerable patient group. The clinical issues that are common in the care of the patient with advanced cancer may raise specific ethical concerns for the nurse. Managing the symptoms with the goal of palliative care in mind will help to frame these concerns more clearly. Communicating with patients and families on an ongoing basis in a clear and sensitive manner will help to ensure that patients' decisions are known and respected. Nurses need to be prepared to assist in these difficult situations. A nursing ethics group is one method that has been found to be effective in developing nurses' expertise in this area.

Adult↗
PubMedDate not supplied

Aging, cancer, and wound healing.

Aging processes can be described as recognizable series of molecular events within vital organ systems whose dysfunction gradually increase with time (reviewed by [1]). This dysfunction manifests itself as abnormal increases and decreases in gene expression and these events occur at a rate that exceeds the relative rate at which they can be corrected. The outcome of this progression is a steady decline in the capacity to successfully maintain an organism's peak physiology, which occurs approximately around the time of sexual maturation. The resulting changes increase the likelihood that an organism will eventually approach a state of increased vulnerability to disease and ultimately leads to death. Within the context of both wound healing and cancer, molecular mechanisms of aging-related changes affect an organism's ability to repair damaged cells and tissues through disregulation of some common molecular pathways. In the case of the former, wound healing is impaired as a result of an inability to adequately express genes which facilitate escape from cell stasis in order to commence and complete the healing process. In the latter case, the failure of a cell's repair mechanism to correct damage to DNA can lead to neoplastic transformation of a normal cell into one with unlimited growth potential. This review compares several of the molecular and cellular events associated with cancer and wound healing during aging.

Aging↗
PubMed2004

ROS stress in cancer cells and therapeutic implications.

Reactive oxygen species (ROS) are constantly generated and eliminated in the biological system, and play important roles in a variety of normal biochemical functions and abnormal pathological processes. Growing evidence suggests that cancer cells exhibit increased intrinsic ROS stress, due in part to oncogenic stimulation, increased metabolic activity, and mitochondrial malfunction. Since the mitochondrial respiratory chain (electron transport complexes) is a major source of ROS generation in the cells, the vulnerability of the mitochondrial DNA to ROS-mediated damage appears to be a mechanism to amplify ROS stress in cancer cells. The escalated ROS generation in cancer cells serves as an endogenous source of DNA-damaging agents that promote genetic instability and development of drug resistance. Malfunction of mitochondria also alters cellular apoptotic response to anticancer agents. Despite the negative impacts of increased ROS in cancer cells, it is possible to exploit this biochemical feature and develop novel therapeutic strategies to preferentially kill cancer cells through ROS-mediated mechanisms. This article reviews ROS stress in cancer cells, its underlying mechanisms and relationship with mitochondrial malfunction and alteration in drug sensitivity, and suggests new therapeutic strategies that take advantage of increased ROS in cancer cells to enhance therapeutic activity and selectivity.

Apoptosis↗