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At least 595 records · Page 33Linked to original sources
PubMed2004

Sequence-specific potentiation of topoisomerase II inhibitors by the histone deacetylase inhibitor suberoylanilide hydroxamic acid.

Acetylation of histones leads to conformational changes of DNA. We have previously shown that the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), induced cell cycle arrest, differentiation, and apoptosis. In addition to their antitumor effects as single agents, HDAC inhibitors may cause conformational changes in the chromatin, rendering the DNA more vulnerable to DNA damaging agents. We examined the effects of SAHA on cell death induced by topo II inhibitors in breast cancer cell lines. Topo II inhibitors stabilize the topo II-DNA complex, resulting in DNA damage. Treatment of cells with SAHA promoted chromatin decondensation associated with increased nuclear concentration and DNA binding of the topo II inhibitor and subsequent potentiation of DNA damage. While SAHA-induced histone hyperacetylation occurred as early as 4 h, chromatin decondensation was most profound at 48 h. SAHA-induced potentiation of topo II inhibitors was sequence-specific. Pre-exposure of cells to SAHA for 48 h was synergistic, whereas shorter pre-exposure periods abrogated synergy and exposure of cells to SAHA after the topo II inhibitor resulted in antagonistic effects. Synergy was not observed in cells with depleted topo II levels. These effects were not limited to specific types of topo II inhibitors. We propose that SAHA significantly potentiates the DNA damage induced by topo II inhibitors; however, synergy is dependent on the sequence of drug administration and the expression of the target. These findings may impact the clinical development of combining HDAC inhibitors with DNA damaging agents.

Acetylation↗
PubMed1984

Vascular endothelium as the vulnerable element in tumours.

The difference between blood vessels in tumours and normal tissues has been recognised for a long time, but little has been done to exploit this in cancer therapy. An overview is presented of the possible contribution of vascular mediated injury with several existing forms of treatment. Interventive radiology and, to some extent, hyperthermia are most obviously mediated through ischaemic cell death. The successful cure of many tumours with radiation, and the complete regressions seen with systemic chemotherapy may also be partially due to a vascular component of damage. The proliferation characteristics of endothelial cells in normal and tumour blood vessels are summarised. These have been derived from single injections or repeated administration of tritiated thymidine. A very large and consistent difference exists between the turnover times. The tumour endothelium is proliferating 20 to 2 000 times faster than any normal tissue endothelium in the adult. The single exception is the placenta which has even more rapid proliferation than the tumour endothelium. The large difference in proliferation rates, coupled with the poor wall structure, lack of innervation and lack of collateral supply, make the blood vessels an attractive target for tumour therapy. Possible means of utilizing this are outlined.

Animals↗
PubMed2026

The Effect of Pain Catastrophizing on Acupuncture Treatment for Chronic Pain in Cancer Survivors.

CONTEXT: Pain catastrophizing (PC) predicts worse pain outcomes in cancer survivors. However, little is known whether PC influences pain outcomes of nonpharmacological treatments such as acupuncture. OBJECTIVES: This study aimed to assess the impact of PC on acupuncture efficacy for chronic pain in cancer survivors. METHODS: This secondary analysis of PEACE trial used two-sample t-test and Pearson's chi-squared test to analyze the pain outcomes of cancer survivors who received electroacupuncture (EA) or battlefield acupuncture (BFA). PC was measured using Pain Catastrophizing Scale (PCS). The Brief Pain Inventory (BPI) was used to measure pain severity and interference at the primary endpoint (week 12). RESULTS: Among 266 participants, 41 (15.41%) had a high baseline PC. Among those receiving EA, high PC patients had greater reductions in pain severity (-3.9 vs. -2.1, P = 0.006) and pain interference (-3.8 vs. -2.6, P = 0.04) than low PC. PC was not associated with pain outcomes in BFA group (P > 0.05 for both severity and interference). Among patients with high PC, a greater proportion were responders in the EA group than those in BFA group (83.3% vs. 43.5%, P = 0.009). Among low PC patients, there was no significant difference in the proportion of responders between the EA and BFA groups (66.1% vs. 64.5%, P = 0.8). CONCLUSION: We found that cancer survivors with high baseline PC had greater pain reductions with EA than BFA and compared to low PC patients. These findings suggest that EA may serve as a targeted treatment option for vulnerable patients with high PC and further support precision pain management.

Humans↗
PubMed2003

Breast cancer in adolescents and young women.

Breast cancer is very rare in adolescents and very young women. Less than 1% of all breast cancer cases occur before the age of 30 years (Natl Cancer Inst Monogr 16 (1994) 69). Invasive breast cancer occurring in women before the age of 35 years has a more aggressive biological behaviour and is associated with a worse prognosis than in older premenopausal women. Breast cancers in these young women are more frequently poorly differentiated, oestrogen-receptor (ER)-negative, have lymphovascular invasion and high proliferating fractions. Breast-conserving surgery in women <35 years old is associated with a higher risk of local recurrence than in older women. All young women should be considered at moderate-high risk by virtue of their age alone and offered adjuvant therapy. The long-term toxicity of adjuvant therapies is a particular concern when treating these women. The implications of possible fertility impairment and premature menopause require consideration when discussing adjuvant chemotherapy and endocrine therapy. Adolescents and young women are particularly vulnerable to emotional distress and psychosocial problems and should be provided with appropriate support. Young women who are at a potential high-risk of developing breast cancer such as those with germline mutations of BRCA1, BRCA2, TP53, PTEN or who have previously received mantle irradiation for Hodgkin's disease need close follow-up and are candidates for screening from a young age.

Adolescent↗
PubMed2005

Disseminating relevant health information to underserved audiences: implications of the Digital Divide Pilot Projects.

OBJECTIVE: This paper examines the influence of the digital divide on disparities in health outcomes for vulnerable populations, identifying implications for medical and public libraries. METHOD: The paper describes the results of the Digital Divide Pilot Projects demonstration research programs funded by the National Cancer Institute to test new strategies for disseminating relevant health information to underserved and at-risk audiences. RESULTS: The Digital Divide Pilot Projects field-tested innovative systemic strategies for helping underserved populations access and utilize relevant health information to make informed health-related decisions about seeking appropriate health care and support, resisting avoidable and significant health risks, and promoting their own health. IMPLICATIONS: The paper builds on the Digital Divide Pilot Projects by identifying implications for developing health communication strategies that libraries can adopt to provide digital health information to vulnerable populations.

Community-Institutional Relations↗
PubMed2003

[Thromboembolic complications during cisplatin-containing chemotherapy for testicular cancer: a problem in the short and possibly also the long term].

Thromboembolic events in testicular cancer patients during cisplatin-containing chemotherapy, both arterial and venous, pose an important problem for various reasons. First, thromboembolic events can result in considerable morbidity and mortality. Second, thromboembolic events can interfere with the continuation of a potentially curative chemotherapy and thus reduce the chance of cure. Finally, thromboembolic events during chemotherapy may predict vascular events in the long term, either as a sign of irreversible damage or as a sign that the patients involved are vulnerable to vascular damage in general. Therefore, more information is needed about the pathogenetic and predictive factors for and preventive measures against thromboembolic events during and after chemotherapy for testicular cancer.

Antineoplastic Agents↗
PubMed2001

Environmental exposure and cancer in children. A conceptual framework for the pediatrician.

Ultimately, after gathering and assessing all available evidence, pediatricians and health care policymakers must make informed decisions on whether exposure to a specific agent has the potential to cause cancer in children. In the case of DES, for which the results were clear, there was no question that the drug should be taken off the market; however, most cases of suspected carcinogens lack such clear evidence documenting cause and effect. An example of a murky topic is the suspected relationship between residential electromagnetic fields (EMFs) and childhood cancer. Epidemiologic and biologic researchers have tried for more than 2 decades to determine whether exposure to relatively high levels of EMFs poses health hazards, especially cancer in children. Although the preponderance of evidence favors a judgment that this ubiquitous environmental exposure is harmless, concerns remain in many public circles and some scientific ones. Any proposed intervention to remove a potentially carcinogenic agent must be weighed against the cost and inconvenience to the affected community. Pediatricians are placed in a vulnerable position when faced with questions of a carcinogenic potential because of the frequency of claims in the popular literature stating that exposure to a certain product or food is associated with an increased risk for cancer in adults and possibly children. When such studies are published or, more often, released to the press, the strength of the evidence for a causal association with cancer, coupled with the context of the study, should be considered as a reasonable starting point. Better communication models of disseminating cancer-risk information are needed so that the public understands the difference between a weak study that appeared on the local news with little evidence to support a cause-and-effect relationship versus a well-designed study that was published in a peer-reviewed journal and indicates a likely cause-and-effect association.

Carcinogens, Environmental↗
PubMed2000

Distress in MEN 2 family members and partners prior to DNA test disclosure. Multiple endocrine neoplasia type 2.

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant early-onset cancer disorder. In the Netherlands presymptomatic genetic testing for MEN 2 is offered to testees from the age of five years. We report on adults requesting testing for themselves (n=90) and on parents who want an at-risk child to be tested (n=26). Sociodemographic, personality, and attitude characteristics, and levels of psychological distress, were determined for applicants and their partners in the predisclosure phase of testing. These participants showed only mildly increased levels of psychological distress, defined as heightened scores on measures of general and test-related anxiety, and of psychological complaints. Compared with a normal population, high levels of anxiety and health complaints were found in applicants who were younger than 25 years and single, and in persons who generally tended to react to distressful situations with anxiety or depression. These characteristics were particularly evident in young applicants (<25 years). Our study shows that people who feel ambivalent towards DNA testing and who are more vulnerable to psychological distress are more likely to agree to participate in the test as part of a collective application by members of a hereditary cancer family.

Adolescent↗
PubMed2000

Different vulnerability among chromosomes to numerical instability in gastric carcinogenesis: stage-dependent analysis by FISH with the use of microwave irradiation.

Numerical chromosomal abnormalities are a well known characteristic of human cancer, but no "chromosome-wide investigation" encompassing almost all of the chromosomes has ever been reported. Furthermore, although the multistep process of carcinogenesis is widely accepted in human cancer, the stepwise numerical aberration of chromosomes has never been addressed. Touch preparations of 24 (male 20, female 4) surgically resected gastric cancer tissue samples in various stages in terms of depth of invasion were analyzed by fluorescence in situ hybridization using centromere-specific probes including 17 chromosomes, 1-4, 6-8, 10-12, 15-18, 20, X, and Y. Microwave irradiation was performed to increase the sensitivity and specificity of the signal. The depth of the tumor invasion in the gastric wall and histological subtypes were recorded by viewing the histology of the adjacent portion. Numerical chromosomal abnormalities of chromosomes 1 and 2 were found most frequently and from the early stage of gastric cancer. The abnormalities observed were limited to chromosomes 1, 2, 4, and 20 in tumors invading to the middle layer of the submucosa of the gastric wall, but these became more extensive, involving almost all of the chromosomes investigated when the tumor had invaded beyond the proper muscle of the gastric wall. Centromeric numbers of chromosomes 3 and 18 were exceptionally stable even after the tumor progressed to advanced stage. These profiles of the sequential process of numerical chromosomal abnormality were similar in both mucocellular and tubular-type gastric cancer, but the prevalence was significantly lower in the mucocellular type (39.0% versus 68.0%). On the basis of fluorescence in situ hybridization analysis of 17 different chromosome centromeres in gastric cancer in various stages, we conclude that the earliest events in gastric carcinogenesis in terms of chromosomal abnormality occur in chromosomes 1 and 2 and that chromosomal numerical aberrations expand in a stepwise manner with cancer progression.

Adult↗
PubMed1994

Cell cycle control and cancer chemotherapy.

As detailed information accumulates about how cell cycle events are regulated, we can expect new opportunities for application to cancer therapy. The altered expression of oncogenes and tumor suppressor genes that commonly occurs in human cancers may impair the ability of the cells to respond to metabolic perturbations of stress. Impaired cell cycle regulation would make cells vulnerable to pharmacologic intervention by drug regimens tailored to the defects existing in particular tumors. Recent findings that may become applicable to therapy are reviewed, and the possible form of new therapeutic stratagems is considered.

Cell Cycle↗
PubMed2006

The impact of newly diagnosed chronic paediatric conditions on parental quality of life.

OBJECTIVE: Parental functioning and well-being are important aspects of a family's adaptation to chronic paediatric conditions. This study investigates the effects of diagnosis (cancer vs. diabetes/epilepsy) and time since diagnosis on parental quality of life (PQL). METHODS: 122 parents (66 mothers, 56 fathers), whose children were diagnosed and treated for one chronic disease, filled in the Ulm Quality of Life Inventory for Parents twice within the first three months after the initial diagnosis. The effects of diagnosis and time (1-2 weeks and 2-3 months after diagnosis) on PQL were analysed separately for mothers and fathers. RESULTS: Parents of a child with cancer consistently reported lower PQL compared with parents of a child with diabetes/epilepsy. Only the fathers' well-being increased significantly within the first three months after the child was diagnosed for a chronic disease. However, in most of the PQL domains there was a persistent impairment within the time-frame of this study. Parents of children with a chronic disease were more satisfied with their family situation than healthy controls. Age of the child was positively correlated with PQL. CONCLUSIONS: A diagnosis of cancer, especially in young children, has a strong negative effect on PQL. Measuring PQL in a preventive approach would help to identify vulnerable parents and to provide psychosocial support in time.

Adaptation, Psychological↗
PubMed2005

Mitochondrial DNA in somatic cells: a promising target of routine clinical tests.

Alterations of mitochondrial DNA have long been considered only from a point of view of rare genetic disorders causing neuromyopathy. Recently, alterations of mitochondrial DNA have been found in so-called common diseases such as heart failure, diabetes, and cancer; some of these alterations are inherited, and some are generated and/or accumulated in somatic cells with age. Mitochondrial DNA is more vulnerable to alteration than is nuclear DNA. For example, mitochondria produce a large amount of reactive oxygen species as an inevitable byproduct of oxidative phosphorylation. Therefore, mitochondrial DNA is under much stronger oxidative stress than is nuclear DNA. In spite of the importance, it is much less elucidated in the mitochondrial genome than in the nuclear genome how the genome is maintained. In this review, we focus on maintenance of mitochondrial DNA in somatic cells and its clinical importance.

Animals↗
PubMed2003

Abdominal malignancies in patients with Wilson's disease.

BACKGROUND: Wilson's disease is associated with heavy copper overload, primarily in the liver. Copper is a toxic metal, and might be expected to be associated with cancer induction, as iron is in haemochromatosis. However, liver cancer is currently believed to be extremely rare in this disease, and other intra-abdominal malignancies have not been reported. AIM: To assess the frequency of abdominal malignant disease in patients with Wilson's disease on long-term follow-up. DESIGN: Retrospective study in two specialist Wilson's disease clinics: Cambridge/London and Uppsala. METHODS: We reviewed the case records of 363 patients seen at three centres: Addenbrooke's Hospital, Cambridge, 1955-1987; the Middlesex Hospital, London, 1987-2000; and the University Hospital, Uppsala, Sweden, 1966-2002. Patients were grouped by length of follow-up: 10-19 years; 20-29 years; 30-39 years; and 40 years or more. RESULTS: No cancers were seen in patients followed for <10 years. For patients in the 10-19 years group, the frequency was 4.2%; at 20-29 years, it was 5.3%; and at 30-39 years, 15%. No cancers were seen in the 40+ years follow-up group. The cancers consisted of hepatomas, cholangiocarcinomas, and poorly differentiated adenocarcinomas of undetermined primary site. DISCUSSION: Patients with Wilson's disease appear to be vulnerable to the formation of aggressive malignant intra-abdominal tumours during long-term follow-up, irrespective of treatment. Ultrasound scanning of the abdomen seems to be a useful screening procedure.

Abdominal Neoplasms↗
PubMed1997

Socioeconomic deprivation and health in Glasgow and the west of Scotland--a study of cancer incidence among male residents of hostels for the single homeless.

STUDY OBJECTIVE: To determine the incidence of cancer among homeless men in Glasgow. DESIGN: Descriptive study of cancer incidence in a defined, though individually unidentifiable, population cohort. SETTING: Glasgow and the West of Scotland Region. PARTICIPANTS: Male residents of 10 hostels for the single homeless in Glasgow, open for all or part of the period 1975-93. Estimated total man-years of risk 21,820. MAIN RESULTS: After adjusting for age and socioeconomic deprivation, the proportional incidence ratio (PIR) of tumours of the oral cavity and pharynx in hostel residents was over twice what would be expected in the male population as a whole (PIR 2.37, 95% CI 1.41, 4.00). Cancers of the oesophagus and larynx were also overrepresented (PIR 1.63 and 1.74 respectively). Estimated age standardised incidence ratios were greater than would be expected for the most socioeconomically deprived areas of the west of Scotland for tumours of the oral cavity and pharynx, larynx, oesophagus, and lung (2.39, 1.87, 1.61, and 1.23 respectively). CONCLUSIONS: The incidence of many cancers is known to be higher in lower socioeconomic groups. Within the lowest deprivation category, there is evidence from this study for a further excess risk among homeless men for cancers of the oral cavity and pharynx, oesophagus, larynx, and lung. Improvements in general health care are urgently needed for this particularly vulnerable section of the population.

Cohort Studies↗
PubMed2004

RNAi and HTS: exploring cancer by systematic loss-of-function.

Cancer develops through the successive accumulation and selection of genetic and epigenetic alterations, enabling cells to survive, replicate and evade homeostatic control mechanisms such as apoptosis and antiproliferative signals. This transformation process, however, may create vulnerabilities since the accumulation of mutations can expose synthetic lethal gene interactions and oncogene-driven cellular reprogramming ('addiction'), giving rise to new therapeutic avenues. With the completion of the human genome project, it is anticipated that the identification and characterization of genetic networks that regulate cell growth, differentiation, apoptosis and transformation will be fundamental to decoding the complexity of these processes, and ultimately, cancer itself. Genomic methodologies, such as large-scale mRNA profiling using microarrays, have already begun to reveal the molecular basis of cancer heterogeneity and the clinical behavior of tumors. The combination of traditional cell culture techniques with high-throughput screening approaches has given rise to new cellular-genomics methodologies that enable the simultaneous interrogation of thousands of genes in live cells, facilitating true functional profiling of biological processes. Among these, RNA interference (RNAi) has the potential to enable rapid genome-wide loss-of-function (LOF) screens in mammalian systems, which until recently has been the sole domain of lower organisms. Here, we present a broad overview of this maturing technology and explore how, within current technical constraints, large-scale LOF use of RNAi can be exploited to uncover the molecular basis of cancer--from the genetics of synthetic lethality and oncogene-dependent cellular addiction to the acquisition of cancer-associated cellular phenotypes.

False Negative Reactions↗
PubMedDate not supplied

The effects of hyperthermia in bone marrow purging of breast cancer.

The number of autologous bone marrow transplants done for solid tumours, particularly breast cancer, has risen steadily over the last ten years. The role of bone marrow or peripheral blood progenitor cell purging in transplantation is incompletely understood. Theoretically, the reinfusion of untreated bone marrow containing tumour cells might result in relapse in some patients treated with high-dose chemotherapy and hematopoietic support. Therefore, safe and effective purging techniques may increase long-term, disease-free survivorship. In this study, hyperthermia was evaluated for its ability to purge CAMA-1 breast cancer cells from normal human bone marrow. Between two and nine trials of a range of temperatures (42-45 degrees C) and durations of treatment (1-4 h) were performed. The effect of hyperthermia on normal bone marrow alone and in mixes with breast cancer cells was also evaluated. Hyperthermia (45 degrees C, 4 h) produced > 5 logs of CAMA-1 cell kill. Exposures of 45 degrees C for 2 h and 44 degrees C for 4 h resulted in approximately three logs of cell kill, corresponding to < 1% survival of clonogenic cells. Normal bone marrow was considerably more vulnerable to heat treatments, however, with approximately 1% of progenitors remaining clonogenic after exposure of 43 degrees C for 2 h and 44 degrees C for 1 h. Therefore, although hyperthermia is able to achieve adequate CAMA-1 breast cancer cell kill, it remains more toxic to normal bone marrow as a purging method. To make hyperthermia useful in purging systems, mechanisms to selectively alter thermal sensitivity must be pursued.

Bone Marrow Purging↗
PubMed2003

Leading the Way in Exercise and Diet (Project LEAD): intervening to improve function among older breast and prostate cancer survivors.

The U.S. population is aging, bringing with it an increased prevalence of chronic disease and concomitant declines in physical function. The risk of developing cancer increases significantly with age, and functional decline is much more likely once a cancer diagnosis is rendered. Thus, functional status in later life is a key concern, one that is heightened among elders who have been diagnosed with cancer. To date, however, there have been few trials that have exclusively addressed issues related to cancer survivorship among older cancer patients, and to our knowledge, none has focused on preserving or enhancing physical functioning. This paper describes the study design and methodological considerations of a randomized controlled trial to determine if a personally tailored workbook and telephone counseling program can positively affect physical activity and dietary behaviors and ultimately the physical functioning of up to 420 older men and women newly diagnosed with breast or prostate cancer. This trial is unique because the cancer diagnosis is used not only as a marker of risk for functional decline, but also as a "teachable moment" - an opportune time when elders may be more receptive to making beneficial lifestyle changes. Undoubtedly, as cure rates for cancer increase and intersect with ever-growing numbers of elderly, there will be numerous opportunities to provide and test interventions within this vulnerable population and to target functional status as a primary outcome. In reporting our methods, we hope to give others "a leg up," so that they can hurdle with greater ease the barriers we experienced, and thus advance the field more rapidly.

Aged↗