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PubMedDate not supplied

Pegylated zinc protoporphyrin: a water-soluble heme oxygenase inhibitor with tumor-targeting capacity.

Heme oxygenase (HO) is a key enzyme in heme metabolism; it oxidatively degrades heme to biliverdin, accompanied by formation of free iron and carbon monoxide. Biliverdin is subsequently reduced by cytosolic biliverdin reductase to form bilirubin, a potent antioxidant. We recently found that tumor cells utilize HO to protect themselves from oxidative stress by producing the antioxidant bilirubin. This result suggested an important potential therapeutic strategy: suppression of bilirubin production with the use of HO inhibitors; hence, cancer cells become vulnerable to oxidative stress induced by anticancer drugs or leukocytes of the host. This concept was validated by using the intraarterial administration of an HO inhibitor, zinc protoporphyrin, in nonphysiological solution. In the present study, zinc protoporphyrin (ZnPP) was conjugated with poly(ethylene glycol) (PEG) with molecular weight of 5000, to make ZnPP, a water-soluble compound (PEG-ZnPP), and to improve its tumor-targeting efficiency. PEG was conjugated to ZnPP through newly introduced amino groups, where ethylenediamine residues were added at C6 and C7 of protoporphyrin. The divalent zinc cation was chelated into the protoporphyrin ring to obtain PEG-ZnPP. PEG-ZnPP did become highly water-soluble, and it formed multimolecular associations with molecules larger than 70 kDa in aqueous media. PEG-ZnPP inhibited splenic microsomal HO activity in vitro in a competitive manner in the presence of hemin, with an apparent inhibitory constant of 0.12 microM. Most important, PEG-ZnPP injected intravenously significantly suppressed intratumor HO activity in a murine solid tumor model, which suggests that tumor-targeted inhibition of HO is possible with the use of PEG-ZnPP.

Animals↗
PubMed2004

Outcomes research in lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer death in the United States. Most therapeutic interventions for this disease achieve modest benefits, but at the expense of nontrivial toxicity and cost, making it an important area for outcomes analysis. OBJECTIVE: The goal of the study was to audit the literature of outcomes pertaining to lung cancer. DATA SOURCES: The English language outcomes literature published during the period from 1990 through 2000 was systematically reviewed and analyzed. STUDY SELECTION: Papers had to contain original research in one of the following areas: quality of life, health economics, communication, decision making, quality of care, or patient satisfaction. DATA EXTRACTION: The literature was reviewed and analyzed by the author. DATA SYNTHESIS: The lung cancer outcomes literature is growing rapidly. Of the 199 studies examined, 106 (53%) dealt primarily with quality-of-life measurement, 69 (35%) examined costs, 11 (6%) dealt with communication and decision making, 11 (6%) assessed the quality of care, and two (1%) evaluated patient satisfaction. Most studies focused on the palliative phase of care. Women, the elderly, and minorities were generally well represented in these studies. The European Organization for Research and Treatment of Cancer QLQ-C30 with its LC13 module is emerging as the most commonly employed quality-of-life instrument in lung cancer studies. Economic studies vary widely in their quality. The literature is relatively sparse with respect to quality of care, communication, and decision making, however. CONCLUSIONS: A substantial body of outcomes research has been published since 1990. Further work is needed in the area of methods development, in the assessment of the impact of new technologies, and in the monitoring of the quality of lung cancer care in vulnerable populations.

Health Care Costs↗
PubMed2006

Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis.

The disease state of cancer appears late in tumor development. Before being diagnosed, a tumor can remain for prolonged periods of time in a dormant state. Dormant human cancer is commonly defined as a microscopic tumor that does not expand in size and remains asymptomatic. Dormant tumors represent an early stage in tumor development and may therefore be a potential target for nontoxic, antiangiogenic therapy that could prevent tumor recurrence. Here, we characterize an experimental model that recapitulates the clinical dormancy of human tumors in mice. We demonstrate that these microscopic dormant cancers switch to the angiogenic phenotype at a predictable time. We further show that while angiogenic liposarcomas expand rapidly after inoculation of tumor cells in mice, nonangiogenic dormant liposarcomas remain microscopic up to one-third of the normal severe combined immune deficiency (SCID) mouse life span, although they contain proliferating tumor cells. Nonangiogenic dormant tumors follow a similar growth pattern in subcutaneous (s.c.) and orthotopic environments. Throughout the dormancy period, development of intratumoral vessels is impaired. In nonangogenic dormant tumors, small clusters of endothelial cells without lumens are observed early after tumor cell inoculation, but the nonangiogenic tumor cannot sustain these vessels, and they disappear within weeks. There is a concomitant decrease in microvessel density, and the nonangiogenic dormant tumor remains harmless to the host. In contrast, microvessel density in tumors increases rapidly after the angiogenic switch and correlates with rapid expansion of tumor mass. Both tumor types cultured in vitro contain fully transformed cells, but only cells from the nonangiogenic human liposarcoma secrete relatively high levels of the angiogenesis inhibitors thrombospondin-1 and TIMP-1. This model suggests that as improved blood or urine molecular biomarkers are developed, the microscopic, nonangiogenic, dormant phase of human cancer may be vulnerable to antiangiogenic therapy years before symptoms, or before anatomical location of a tumor can be detected, by conventional methods.

Animals↗
PubMed1996

Patient advocacy: a role for nurses?

There is much controversy surrounding the issue of nurses in the role of patient advocate. Cancer patients are vulnerable due to their diagnoses, the anxiety that it generates, the nature of the disease and subsequent treatment and may diminished autonomy as a result. It is questionable whether the nurse is able to promote the best interest of the patient in this situation. Models of advocacy and the nurse-patient relationship are discussed. The main arguments for taking on the role of patient advocate include: reference to long periods of time spent with patient and the chance to build a relationship; on duty to care and the duty to do no harm. Criticisms of the appropriateness of advocacy role for nurses include: inability for the patient to choose his or her nurse; promotion of self interests; charges of paternalism; challenges from other health care professionals and multiple and/or conflicting obligations. It is concluded that perhaps the most ethical way of caring is by empowering patients and promoting self-advocacy. This concept needs to be further explored.

Ethics, Nursing↗
PubMed1994

Deaths and complications following prostatectomy in 1400 men in the northern region of England. Northern Regional Prostate Audit Group.

OBJECTIVE: To determine the degree of variation in mortality and major morbidity following transurethral resection of the prostate (TURP), and to assess intersite variation for mortality and morbidity over 12 sites within the Northern Region. Further, to determine whether the previously observed effects on morbidity of unit size, patient through-put and emergency admission were borne out in contemporary urological practice in the Northern Region. PATIENTS AND METHODS: For an 8 month period, 1 April 1991-31 November 1991, an independent audit of TURP was performed on 12 different hospital sites throughout the Northern Region. A constant data set was designed which was collected on each patient before and 3 months after operation by two independent clinical co-ordinators who travelled to each of the sites. All case notes were reviewed at 3 months after operation by the co-ordinators using a standard proforma, rather than depending upon self reporting by medical staff. Data on factors potentially affecting mortality and morbidity were collected, including emergency admission, diagnosis of prostate cancer, American Society of Anesthesiologists' co-morbidity scores, and age and differences in throughput in the 12 sites. The effect of through-put or 'volume' on mortality and morbidity was assessed by comparing morbidity and the number of cases performed. RESULTS: The early mean death rate was 13 of 1396 patients (0.9%), with an inter-site variation ranging from 0% to 3.8%. A mean of 2.0% of men were returned to theatre after TURP, 2.4% of patients received a blood transfusion (> 2 units) after operation, and 8.0% of patients developed post-operative sepsis; these complications varied sixfold, sevenfold and 17-fold across the different sites respectively. Those units performing < or = 100 operations over the audit period (equivalent to < 150 operation per year) had a significantly increased rate of deaths and complications which was not related to population differences, though some low volume units had good results. Elderly men who were admitted as emergencies or with prostate cancer were particularly vulnerable to complications. CONCLUSIONS: The overall early mortality rate after TURP for benign prostatic hyperplasia across the Region compares well with other reported large series. The significant variation in morbidity rates found in this study suggests that careful attention needs to be paid by Urologists, Purchasers and Providers to morbidity rates after prostatectomy.

Age Factors↗
PubMed2002

The effect of an educational intervention on promoting breast self-examination in older African American and Caucasian women.

PURPOSE/OBJECTIVES: To test the efficacy of innovative, age- and race-sensitive, self-monitored, video breast health kits in increasing knowledge about breast cancer risk and screening and breast self-examination (BSE) proficiency. DESIGN: Quasi-experimental pretest and post-test design. SETTING: Dual-site study in community-based settings in the Northeast and Southeast United States. SAMPLE: 328 women (206 in the intervention group, 122 in the control group) aged 60 or older; predominantly African American (77%); mean education of 10.8 years; annual income below $10,000 (50%). METHODS: Individual pretest and post-test interviews conducted by nurses at two-week intervals assessed knowledge about breast cancer risk and screening and BSE proficiency as demonstrated on vested breast models. Intervention subjects used video breast health kits in ethnic editions designed for the study. Control subjects received educational pamphlets. MAIN RESEARCH VARIABLES: Dependent variables were knowledge about breast health and BSE proficiency measured by demonstration of inspection and palpation skills and detection of lumps in a simulation model. FINDINGS: Three multiple analyses of covariance revealed statistically significant differences in outcome variables between the intervention and control groups. CONCLUSIONS: The intervention was effective in increasing knowledge about breast cancer risk and screening and BSE proficiency in this sample of older women. IMPLICATIONS FOR NURSING: These and other educational interventions designed specifically for age and race sensitivity may enhance cancer screening with vulnerable populations. Future studies with more diverse multicultural groups are needed to improve understanding of how to best influence breast health behaviors of older women.

Black or African American↗
PubMed2005

Identifying barriers and facilitating factors to improve screening mammography rates in women diagnosed with mental illness and substance use disorders.

Little is known about screening mammography rates among women diagnosed with mental illness-even though some studies have suggested that this population might be particularly vulnerable to breast cancer. The purpose of this pilot study was to identify facilitators and barriers to mammography among women diagnosed with mental illness and/or substance use disorders. Four focus groups were conducted, with a total of 26 women, ages 40-65 years, with mental illness and/ or substance use disorders. Analysis was performed using the grounded-theory editing approach. Several major themes emerged from the transcripts: (1) motivators for obtaining mammograms, (2) fears and concerns, (3) shame and embarrassment, (4) the clinical environment, (5) provider-patient communication, and (6) the need for increased patient education. A family history of breast cancer and/or cancer was the most powerful motivator among focus group participants for obtaining a mammogram. Doctor recommendations and referrals were also identified as key facilitating factors. The overall knowledge of mammography and breast cancer among these women suggested educational deficiencies-despite extensive breast cancer screening and awareness campaigns. The findings highlight the importance of patient education as well as the positive effects of physician recommendations to encourage patients to receive breast cancer screening.

Adult↗
PubMed2000

[Invasive hepatosplenic hyalohyphomycosis. Report of a case].

Invasive fungal infections are an increasingly common problem in patients with cancer and other vulnerable groups. We report a case of hepatosplenic hialohifomycosis probably by Aspergillus sp. In a patient with acute leukemia, and prolonged neutropenia, treated with corticosteroids and broad spectrum antibiotics. A review concerning diagnosis, clinical course and treatment of this condition is presented.

Acute Disease↗
PubMedDate not supplied

[Life events and breast cancer. Initial results of a comparative study dealing with 100 cases and their control].

The authors present the first results of a case-control study relative to the importance of life events in the 5 years which precede the clinical apparition of breast cancer. This study has examined a group of 100 women of french origin, aged from 45 to 65 years and carriers of a breast cancer which had been diagnosed less than a year ago, as well as their controls matched according to age. If the total number of events is similar in the two groups, there appears a negative peak of social desirability events in the two years preceding the diagnosis of cancer. The quantification of event impact by the subjects shows a greater vulnerability in women with cancer.

Aged↗
PubMed1998

Activities of the enzymes participating in purine and free-radical metabolism in cancerous human colorectal tissues.

Activities of adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide dismutase, glutathione peroxidase and catalase enzymes were measured in cancerous and non-cancerous adjacent colorectal tissues from 10 patients. Activities of DNA turn-over enzymes (ADA, 5'NT and XO) were found increased and those of free-radical metabolizing enzymes (SOD, GSH-Px and CAT) decreased in cancerous tissues compared with those of non-cancerous adjacent ones. Malondialdehyde (MDA) concentrations in cancerous tissues were also found higher than those of non-cancerous tissues, which indicated accelerated lipid peroxidation in the cancerous tissues. In the correlation analysis, disordered enzymatical relations were observed between the enzymes of both metabolic pathways. Results suggest that activities of purine metabolizing enzymes increase to cope with accelerated purine metabolism in cancerous tissues and, enzymatic antioxidant defense potential of cancerous tissues decreases due to carcinogenic processes in the tissues. Reduced antioxidant defense system makes the cancerous tissue more vulnerable to toxic effects of some free-radical species.

5'-Nucleotidase↗
PubMed1999

Specific worry about breast cancer predicts mammography use in women at risk for breast and ovarian cancer.

This longitudinal study examined predictors of mammography use among women with a family history of breast cancer participating in a risk assessment and surveillance program (N = 213). Assessed were background variables (age, prior mammography utilization), cognitive variables (perceived vulnerability), and affective variables (cancer worry and general distress). Results of logistic regression analyses predicting adherence 1 year after baseline contact, in which variables of prior utilization, feelings of vulnerability, and general distress were controlled for, indicated that cancer worry and age were significant predictors of mammography adherence. Results suggest that moderate levels of cancer worry facilitate, rather than undermine, adherence. The results have implications for the construction of educational messages that should be designed to acknowledge feelings of cancer-specific worry and to provide guidance in health protective behaviors.

Adult↗
PubMed2000

Workshop to identify critical windows of exposure for children's health: cancer work group summary.

We considered whether there are discrete windows of vulnerability in the development of cancer and which time periods may be of the greatest importance. Cancer was considered broadly, including cancers in childhood as well as adult cancers that may have an in utero or childhood origin. We concluded that there was evidence from animal and epidemiologic studies for causal relationships for preconceptional, in utero, and childhood exposures and cancer occurrence in children and adults. However, the evidence is incomplete and all relevant critical windows may not have been identified. The comprehensive evaluation of the relative importance of specific time windows of exposure is limited. Improvements in the design of epidemiologic studies and additional animal studies of mechanisms are warranted.

Adolescent↗
PubMed2000

Living in a High-Risk Family.

In this presentation, I share my experiences as a fourth generation breast cancer survivor and, subsequently, as an ardent advocate of breast cancer issues. My presentation is informed, in great part, by the experiences of my great-grandmother, grandmother, mother, and three sisters, all of whom suffered the ravages of breast cancer. It is informed, in even greater part, by my own bout with breast cancer with which I was initially diagnosed at the age of thirty-two. Despite two separate mastectomies, I have survived the disease for more than nineteen years. This presentation, therefore, identifies issues associated with a genetic predisposition to breast cancer, highlights the particular vulnerability of African American women, and advocates awareness and education as a key to breast cancer survivorship. Genetic predisposition to breast cancer dictates precautions of which women of all races and nationalities must be aware. This presentation utilizes the most recent data in identifying and assessing the efficacy of those precautions, including mammography, self-breast examination, diet, drug therapy, and surgery. It also reviews the role of scientific studies and clinical trials in the prevention, diagnosis, and treatment of breast cancer. Developments in genetic mapping are particularly promising. My broad experience with breast cancer led to my founding the Breast Cancer Resource Committee, a non-profit organization that has as its purpose the provision of education initiatives and support, particularly for African American women, who bear an unequal burden in the war against breast cancer. While breast cancer is the second leading cause of cancer death among all women, it is the leading cause of cancer death among African American women. Although awareness and early precautions do not necessarily prevent breast cancer, they remain central to breast cancer survivorship. My own family history, as well as the 1.3 million breast cancer survivors in my country, documents this reality.

Journal Article↗
PubMed2003

The impact of head and neck cancer and facial disfigurement on the quality of life of patients and their partners.

BACKGROUND: Psychological and physical stresses from head and neck cancer can be substantial for patients and partners. There is minimal research exploring treatment impact, particularly facial disfigurement after surgery. MATERIALS AND METHODS: Twenty-eight surgery and radiotherapy/brachytherapy/chemoradiation patients and 25 of their partners were compared with 23 radiotherapy/brachytherapy patients and 19 partners. Participants completed the Hospital Anxiety and Depression Scale, Psychosocial Adaptation to Illness Scale, Dyadic Adjustment Scale, and European Organisation for Research and Treatment of Cancer Quality Of Life Scale, including the Head and Neck Cancer module. The Dropkin Disfigurement and Dysfunction scale classified surgical impairment. RESULTS: Partners reported greater distress than patients on some scales. Patients did not have a lower quality of life compared with normal populations and other cancer patients. However, on the EORTC they did and were comparable to a normed sample of head and neck cancer patients. Treatment modality was not predictive of psychological vulnerability. DISCUSSION: Head and neck cancer patients do not necessarily experience poor quality of life. The disease can have a significant impact on partners.

Adaptation, Psychological↗
PubMed2000

Aging and cancer in America. Demographic and epidemiologic perspectives.

It has been stated in this article and elsewhere that cancer patients aged 65 years and older deserve special attention as a target group for research efforts across the cancer-control spectrum. The available data show that the vulnerability of older persons to cancer is unmistakable. Clinicians will be treating more older patients as the nation ages. The future needs of this segment of the population must be anticipated. In this context, the following generic treatment questions are pertinent. What are the peculiarities of the aged host of which clinicians must be aware in evaluating the older cancer patient? Do various forms of cancer present differently in the elderly? How can be complications caused by the multiple pathologies inherent in the older patient be anticipated? What are the potential hazards and limitations of surgery, radiotherapy, and chemotherapy for older persons with cancer? What is known regarding increased risk of adverse reactions to medications, drugs, and interaction of drugs in older patients? The surveillance data and population estimates and projections presented in this article illustrate the extent of the problems of cancer in the elderly at the macro level. For the individual patient, the special knowledge of aging individuals and their health status based on geriatric medicine and gerontology that has been accumulating for the past several decades needs to be incorporated into the oncology armamentarium that has developed during the same period. The information and expertise from both fields must converge, and new knowledge must be developed at the aging/cancer interface and applied for the optimal treatment of cancer in the elderly.

Aged↗
PubMedDate not supplied

Facilitating care for childhood cancer survivors: integrating children's oncology group long-term follow-up guidelines and health links in clinical practice.

Childhood cancer survivors are a growing, vulnerable group with health care needs unique to their cancer treatments. They may experience many late physical and psychological complications (late effects) of treatment including organ dysfunction, infertility, second neoplasms, chronic hepatitis, musculoskeletal problems, alterations in cognitive function, and myriad psychosocial problems. Health care providers may be unaware of actual or potential survivor problems. Until recently, there were no clearly defined, easily accessible risk-based guidelines for cancer survivor follow-up care. This article will use a case-study approach to demonstrate how the newly developed Children's Oncology Group Long-term Follow-up Guidelines and Health Links can be used in clinical practice to improve awareness about late effects and the importance of follow-up care for childhood cancer survivors. The Children's Oncology Group Guidelines and Health Links were created by a multidisciplinary team of health care experts and patient advocates to provide a systematic plan for pediatric cancer survivor follow-up care and health education across the cancer continuum.

Adolescent↗
PubMed2026

Loss of BOK increases vulnerability of p53 deficient non-small cell lung cancer cells to ATR inhibition through its role in uridine metabolism.

BOK is a pro-apoptotic member of the BCL-2 family frequently repressed in cancer and with emerging roles beyond apoptosis. BOK interacts with and increases uridine monophosphate synthetase (UMPS) activity, thereby promoting uridine monophosphate (UMP) synthesis. We previously showed that BOK protein is downregulated in primary human lung cancer samples, correlating with poorer patient survival. Here, we demonstrate that BOK deficiency increases DNA damage, triggering p53 activation and cell cycle arrest in two independent non-small cell lung cancer (NSCLC) cell models that express either WT or defective p53. In a p53-deficient setting, BOK loss caused elevated baseline DNA damage rendering cells more dependent on alternative DNA repair pathways. We exploited this vulnerability by inhibiting the ATR-mediated DNA damage response pathway with the selective ATR inhibitor ceralasertib (AZD6738). ATR inhibition in BOK/p53 compound-deficient NSCLC cells exacerbated DNA damage and induced cell death, indicating a synthetic lethal interaction. The DNA damage in BOK-deficient cells was rescued by a cell permeable BOK-BH3-derived peptide, confirming the mechanistic link between BOK and UMPS. Taken together, our findings reveal a vulnerability in NSCLC, where combined loss of p53 and BOK sensitises cells to ATR inhibition. This synthetic interaction suggests that p53-deficient tumours with reduced BOK expression may be more reliant on ATR-mediated DNA repair, providing a mechanistic basis for their susceptibility to ATR inhibitors. Given the frequent inactivation of p53 in lung cancer, our study offers a rationale for clinical exploration of ATR inhibitors, in combination with standard chemotherapy, in the context of reduced BOK function. Future investigations into the broader role of BOK in genomic stability and nucleotide metabolism may uncover additional therapeutic strategies for cancers with repressed BOK.

Humans↗
PubMed1996

Experiencing existential changes: the lived experience of having cancer.

This phenomenological study was designed to explore the lived experience of having cancer, as perceived by people who have been diagnosed and treated for cancer. The aim of the study was to add to the knowledge and understanding of this complex human phenomenon. Data were collected through in-depth interviews with nine people who were in the remission or recovery phase of cancer. The interviews were tape-recorded and transcribed verbatim for each participant. Through intersubjective interactions and thematic analysis, the essential description of the lived experience of having cancer was constructed. The overriding theme of the lived experience of having cancer is "experiencing existential changes." Five basic subthemes were identified in the participants accounts, all of which are part of the existential changes involved in the lived experience of having cancer. These are: uncertainty, vulnerability, isolation, discomfort, and redefinition. The study can increase the understanding of what it is like to have cancer.

Adaptation, Psychological↗