Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cancer drivers”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed2002

Controlling cancer pain in primary care: the prescribing habits and knowledge base of general practitioners.

During recent years, the national policy of the United Kingdom has increasingly recognized the central place of general practitioners (GPs) in the care of cancer patients, from screening and early diagnosis through to palliative care and bereavement. There are, however, continuing reports of poor control of pain and other symptoms in the community. To investigate general practitioners' prescribing habits and knowledge of some key pain control issues in advanced cancer, a postal questionnaire surveyed a random sample of 450 East Anglian GPs. The response rate was 73.3%. Most respondents were familiar with the modern management of cancer pain, including the World Health Organization approach, the use of oral opioids, and the management of bone pain. There was less awareness of the drug options available for more uncommon situations, especially the dose conversion of oral morphine to subcutaneous diamorphine and drugs that may be used in syringe drivers. GPs in the UK are familiar with the management of the more common pain control problems. However, it is not appropriate to expect GPs to know the details of management of more unusual cancer pain problems. Specialist clinicians need to make themselves readily available to advise their generalist colleagues. The educational implications for GPs are discussed.

Adult↗
PubMed1985

Occupation and bladder cancer in males: a case-control study.

A case-control study of 512 male cases of bladder cancer and 596 male hospital controls (all living in the province of Turin, Northern Italy, an area with a high proportion of car workers) has been analyzed for occupations. Relative risks were 1.8 (95% c.l. 0.9-3.6) for the textile industry, 3.8 (1.3-11.5) for the leather industry, 1.8 (0.8-4.0) for printing, 8.8 (2.7-28.6) for dyestuff production, 1.2 (0.6-2.4) for tire production and 2.5 (1.0-6.0) for other rubber goods, 2.0 (0.9-4.5) for brickyards and related activities. A relative risk of 3.1 (0.9-10.5) was found for turners having started work before 1940 and with at least 10 years of activity. For truck drivers the relative risk was 1.2 (0.6-2.5). A job-exposure matrix was developed for the development of new hypotheses; an association with bladder cancer was found for aromatic amines only. The attributable risk percent in the population was estimated as 10%, when only those occupations consistently associated with bladder cancer were considered.

Adult↗
PubMed2005

Emergentism as a default: cancer as a problem of tissue organization.

During the last fifty years the dominant stance in experimental biology has been reductionism. For the most part, research programs were based on the notion that genes were in 'the driver's seat' controlling the developmental program and determining normalcy and disease (genetic reductionism and genetic determinism). Philosophers were the first to realize that the belief that the Mendelian genes were reduced to DNA molecules was questionable. Soon after these pronouncements, experimental data confirmed their misgivings. The optimism of molecular biologists, fueled by early success in tackling relatively simple problems, has now been tempered by the difficulties found when attempting to understand complex biological problems. Here, we analyse experimental data that illustrate the shortcomings of this sort of reductionism. We also examine the prevailing paradigm in cancer research, the somatic mutation theory (SMT), the premises of which are: (i) cancer is derived from a single somatic cell that has accumulated multiple DNA mutations; (ii) the default state of cell proliferation in metazoa is quiescence; and (iii) cancer is a disease of cell proliferation caused by mutations in genes that control proliferation and the cell cycle. We challenge the notion that cancer is a cellular problem caused by mutated genes by assessing data gathered both from within the reductionist paradigm and from an alternative view that regards carcinogenesis as a developmental process gone awry. This alternative view, explored under the name of the tissue organization field theory (TOFT), is based on premises that place cancer in a different hierarchical level of complexity from that proposed by the SMT, namely: (i) carcinogenesis represents a problem of tissue organization comparable to organogenesis, and (ii) proliferation is the default state of all cells. We propose that the organicist view, in which the TOFT is based, is a good starting point from which to explore emergent phenomena. However, new theoretical concepts are needed in order to grapple with the apparent circular causality of complex biological phenomena in development and carcinogenesis.

Animals↗
PubMed1993

[Etiology, pathogenesis and epidemiology or urothelial tumors].

A hospital-based case-control study of 531 male and 144 female matched pairs was conducted to analyse the role of nonoccupational and occupational risk factors in the etiology of tumors of the lower urinary tract. Smoking of cigarettes was associated with an increased risk and showed a significant dose- and time-response for both sexes. Heavy pipe smoking also significantly increased the risk. Controlling for smoking, a significantly twofold or more increase in risk was found for heavy consumption of coffee in both sexes and for heavy intake of beer in males. Increasing levels of total fluid intake were associated with increasing, smoking-adjusted risks in men. Significant associations were found for chronic infection of the lower urinary tract, familial history of bladder cancer, and frequent consumption of high fat meals among men and for frequent consumption of canned food in both sexes. With regard to occupational history, significantly elevated risks were found for ever-employment in the printing, plastics and synthetics, rubber, mining and dyestuffs industries, for exposure to spray paints, zinc, chromium/chromate, oils, petroleum and metal dust/fume, and for occupation as mining worker and truck driver among men. Multivariate logistic regression analysis showed-with the exception of fluid intake-significant contribution of the above-mentioned risks factors to the risk of bladder cancer.

Beer↗
PubMed1995

The association of body size and large bowel cancer risk in Wisconsin (United States) women.

Body size is associated with the risk of many diseases, including diabetes, heart disease, and some cancers. To evaluate the association of body size with large bowel cancer, height and weight measurements were ascertained by telephone interview from 779 Wisconsin (United States) women with newly reported diagnoses of carcinoma of the colon and rectum. Controls (n = 2,315) interviewed for this case-control study were selected randomly from Wisconsin driver's license files and Health Care Financing Administration files. The effects of weight and height were examined using multiple logistic regression to control for potential confounding variables. In this study, weight adjusted for height increased the risk of colon cancer (odds ratio [OR] for 72.57-148.33 kg cf 36.29-58.05 kg = 1.4, 95 percent confidence interval [CI] = 1.0-1.9) but did not increase the risk of rectal cancer. Height did not influence risk for cancer of either the colon or the rectum. Left-colon subsite analysis showed especially strong associations with current weight and with percent change in weight since age 18. These data suggest that a dose-response relationship exists between body size and risk of colon cancer in women; body size did not appear to influence risk of rectal cancer.

Adult↗
PubMed1993

Cancer of the large bowel in women in relation to alcohol consumption: a case-control study in Wisconsin (United States).

Age-specific consumption of beer, wine, and liquor was ascertained by telephone interview from 779 women in Wisconsin (United States) with newly reported diagnosis of carcinoma of the colon and rectum. Population controls (n = 2,315) interviewed for this case-control study were randomly selected from Wisconsin driver's license files and Health Care Financing Administration files. Overall, there was a modest indication that high levels of alcohol consumption (11 or more drinks per week) were associated with increased risk of large bowel cancer (adjusted odds ratio [OR] = 1.47, 95 percent confidence interval [CI] = 1.0-2.22). In site-specific analyses, only rectal cancer demonstrated a significant linear trend (P = 0.01) with increasing consumption. Significant beverage-specific effects were observed for liquor and colon cancer: the adjusted ORs for 1-2, 3-5, and 6+ drinks per week were 1.12, 1.68, 1.51, respectively (P trend = 0.01). Beer was associated significantly with rectal cancer: the adjusted ORs for 1-2, 3-5, 6-10, and 11+ drinks per week were 1.25, 1.25, 1.58, 2.42, respectively (P trend = 0.02). Wine consumption was associated inversely with these cancers. These relationships appeared to be consistent for recent, past, and total lifetime consumption, and were not attributable to differences in dietary habits.

Adult↗
PubMed1999

Surveillance of potential associations between occupations and causes of death in Canada, 1965-91.

OBJECTIVE: To detect unsuspected associations between workplace situations and specific causes of death in Canada. METHODS: An occupational surveillance system was established consisting of a cohort of 457,224 men and 242,196 women employed between 1965 and 1971, constituting about 10% of the labour force in Canada at that time. Mortality between 1965 and 1991 has been determined by computerised record linkage with the Canadian mortality database. Through regression analysis, associations between 670 occupations and 70 specific causes of death were measured. RESULTS: There were almost 116,000 deaths among men and over 26,800 deaths among women. About 28,000 comparisons were made between occupations and specific causes of death. With various reporting criteria, several potential associations were highlighted, including: infectious disease mortality among barbers and hairdressers; laryngeal cancer among male metal fitters and assemblers; lung cancer among female waiters; breast cancer among female metal fitters and assemblers; brain cancer among female nursing assistants and male painters; and ischaemic heart disease among female inspectors and foremen and among male taxi drivers and chauffeurs. CONCLUSIONS: When excess risk of mortality is apparent, the intention of this occupational surveillance system is to spark further studies to gain aetiological knowledge.

Adult↗
PubMed1993

Dementia and the older driver.

Many demented patients continue to drive who, as a group, appear to be at increased risk for crashes, when compared with controls. Some studies have shown significant relationships between cognitive and functional measures, driver status performance on driving tests, and crash data. A number of methodologic problems in the studies reduce the level of confidence to which the data can be generalized. Diagnosis is not an adequate predictor of function. There is great heterogeneity of the rate of progress as well as the cognitive strengths and weaknesses among patients with dementing disorders. Performance-based guidelines for driving competence are essential rather than dependence on diagnostic labels. Ultimately, there would be no concern if there were no injury. There would be little concern if our cars and roadways were designed in such a way that the driver played little role in the traffic interaction. The potential for such systems exists but is expensive and unlikely to be built on a large scale. Therefore, it is necessary to identify the characteristics of the drivers who pose "unacceptable" risk to themselves and others. Functional information obtained from the family should be supplemented by an observational assessment of the patient, ideally by a trained specialist. The health care team's goal is to help the aging patient maintain autonomy in the face of declining health and psychosocial status. This outcome relies on a close alliance between physicians, nurses, occupational therapists, psychologists, social workers, and others to understand and manage the functional aspects and complex interactions between aging, disease, and social support systems. Treatment teams with skills in functional assessment and knowledge about the available social services are invaluable in caring for the functionally declining elderly patient. Recommendations to withdraw driving privileges on the basis of a diagnosis of dementia may ultimately be borne out by appropriate studies, but these studies have not been conducted. There is a great need for a consensus process to identify dangerous drivers, ideally with performance-based measures. This would then support uniform laws across the country that protect the patient, the physician, and the public. Education of the medical and lay community of the "warning signs" of declining driving skills could do much to heighten awareness in the community, much as the warning signs of cancer have been publicized. With the aging of our nation's population and the strong association of aging with dementing disorders, there is reason to be concerned, especially when dementing illnesses affect judgment. Demented drivers may pose a significant public health problem.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2006

Relevant molecular markers and targets.

Ovarian cancer is a heterogeneous disease with extensive cytogenetic and molecular heterogeneity including aneuploidy, chromosomal alterations, mutations and overexpression as well as a natural propensity to disseminate and spread, making it difficult to diagnose at an early stage. Insights into the molecular mechanisms operative in cancer development, progression and metastasis have uncovered a wide array of targets for therapeutic intervention. In the absence of a common driving oncogene in ovarian cancer, single targeted therapy for this disease is unlikely to yield significant clinical benefit. Tailored approaches that combine molecular targeting agents with cytotoxic regimens hold great promise when used in primary treatment, during consolidation and maintenance therapy, and in the treatment of persistent or recurrent disease. The most promising treatment strategies are those that target the drivers of tumorigenesis and enhance the activity of cytotoxic agents. Receptor tyrosine kinases, non-receptor tyrosine kinases, serine/threonine kinases, transferases, proteases and deacetylases are among the relevant molecular markers and targets for ovarian cancer that are discussed. Collaboration, coordination, creativity and aggressive outreach to patients and their advocates are essential for success in running the concurrent trials with multiple clinical end points and embedded translational research that are needed to evaluate the array of promising targeted therapeutics and combinations. Validated biomarkers, surrogate specimens and end points, and additional clinically relevant in vitro and in vivo models for ovarian cancer are needed to facilitate the drug development and evaluation process, and ultimately to make meaningful improvements in the diagnosis, prevention and management of ovarian cancer.

Biomarkers, Tumor↗
PubMed2001

A population-based case-control study of carotenoid and vitamin A intake and ovarian cancer (United States).

OBJECTIVE: To evaluate the association between dietary intake of carotenoids and vitamin A and the incidence of ovarian cancer. METHODS: We conducted a population-based case-control study of ovarian cancer in Massachusetts and Wisconsin. Incident cases diagnosed between 1991 and 1994 were identified through statewide tumor registries. We selected community controls at random from lists of licensed drivers and Medicare recipients; 327 cases and 3129 controls were included in the analysis. Data were collected by telephone interview, which included an abbreviated food and supplement list to quantify typical consumption of carotenoids (lutein/zeaxanthin, alpha-carotene, beta-carotene), retinol and total vitamin A at 5 years prior to diagnosis in cases, or to a comparable reference date in controls. Results were adjusted for age, state, and other risk factors. RESULTS: Participants with the highest dietary intake of lutein/zeaxanthin (> or =24,000 microg/week) experienced a 40% lower risk of ovarian cancer (95% CI = 0.36-0.99) compared to those with the lowest intake. Intake of alpha-carotene, beta-carotene, retinol and total vitamin A was unrelated to risk. Among foods, we observed non-significantly lower risks with high consumption of spinach, carrots, skim/lowfat milk and liver. CONCLUSION: These results support previous findings suggesting an inverse relationship between carotenoid intake and ovarian cancer risk.

Adult↗
PubMed1995

Multiple births and risk of breast cancer.

Data from a large, multicenter, population-based case-control study were analyzed to investigate the relation between multiple birth pregnancies and subsequent breast-cancer risk in the gravidas. Women less than 75 years old who had breast cancer were identified from statewide tumor registries in Wisconsin, western Massachusetts, Maine and New Hampshire. Controls aged less than 65 years were selected randomly from lists of licensed drivers, and controls aged between 65 and 74 were selected randomly from lists of Medicare beneficiaries. Information on reproductive history and other factors was obtained by means of telephone interviews. After excluding nulliparous women, 5,880 case subjects and 8,217 controls remained for analysis. Multiple birth pregnancies occurred in 146 cases and 218 controls. Adjusted for the number of full-term pregnancies and other confounders, the odds ratio (OR) for any multiple birth pregnancy was 0.94 (95% confidence interval, 0.75 to 1.17). The null association between multiple birth pregnancies and breast cancer remained if the mother's first pregnancy or last pregnancy resulted in a multiple birth. In addition, no trend in risk emerged for age at first multiple birth or time since last multiple birth. While other investigators have suggested biological mechanisms to explain both protective and detrimental effects of multiple births and subsequent development of breast cancer, this study does not support either assertion.

Adult↗
PubMedDate not supplied

A portable syringe driver: design and applications.

Applications of a battery-operated portable syringe driver are reviewed and the Graseby MS16 device is described. Its value in permitting long-term slow infusion of drugs--in preference to intermittent injections--is illustrated by reference to a variety of uses. In size and weight the driver is small enough to permit a patient to wear it even while leading an active life. A custom integrated circuit and a high-efficiency mechanical drive result in such low power consumption that an inexpensive 9V battery will last for up to three months. Applications include heparin infusion, post-operative analgesia, hormone infusions, cancer chemotherapy, domiciliary analgesia in terminal cancer, antibiotics, neonatal infusions, and in human and animal research. One of the most interesting applications has been in the treatment of thalassaemia, extending life expectancy from about 15 years to an indefinite span. The driver incorporates comprehensive safety features.

Equipment and Supplies↗
PubMed1989

Occupational risks of bladder cancer in the United States: I. White men.

We examined the relationship between occupation and bladder cancer risk using data obtained from interviews conducted with 2,100 white males with bladder cancer and 3,874 population controls during the National Bladder Cancer Study, a population-based, case-control study conducted in 10 areas of the United States. The strongest evidence of increased risk among white men was observed for painters, truck drivers, and drill press operatives. For painters, the overall relative risk was 1.5 [95% confidence intervals (CI) = 1.2-2.0]. Among painters who started working prior to 1930, a significant trend in risk with increasing duration of employment as a painter was apparent; the relative risk for such painters employed 10 or more years was 3.0. For truck drivers and drill press operatives, overall risks were 1.3 (CI = 1.1-1.4) and 1.4 (CI = 0.9-2.1), respectively. We observed a significant, positive trend in risk with increasing duration of employment in each of these occupations, with relative risks peaking at approximately two for long-term workers. Excess risks were also observed for workers in several other occupations. In all, we estimate that 21%-25% of bladder cancer diagnosed among white men in the United States is attributable to occupational exposures.

Adult↗
PubMed2026

The genomic landscape of HER2 negative metastatic breast cancer with loss of estrogen and progesterone receptors.

INTRODUCTION: Loss of estrogen receptor (ER) and/or progesterone receptor (PR) might occur during the metastatic progression of ER positive and HER2 negative (ER+/HER2-) breast cancer (BC), but the underpinning molecular alterations remain elusive. We explored the genomic context of HER2- tumors with ER and/or PR loss to investigate potential drivers and actionable alterations that might help personalize treatment of ER+/HER2- BC. METHODS: We accessed data from metastatic HER2- BC included in the MSK-2018 dataset to compare outcome, tumor characteristics and genomic alterations of BC with loss of ER (ER+/-, n = 66) to those maintaining ER positivity (ER+/+, n = 364) or ER negativity (ER-/-, n = 50). We also compared metastatic ER+/+ BC with loss of PR (PR+/-, n = 111) to those maintaining PR positivity (PR+/+, n = 192) or PR negativity (PR-/-, n = 41). RESULTS: In line with previous reports, ER+/- BC was associated with aggressive clinico-pathological characteristics and poor outcome. ER+/- BC showed significantly higher frequency of TP53 and RB1 mutations and lower frequency of PIK3CA and GATA3 mutations compared to ER+/+. ER+/- or PR+/- status was mutually exclusive with ESR1 mutations and was associated with a significantly higher tumor mutational burden. Moreover, ER+/- BC were enriched in driver alterations in the genes of the Notch and Retinoblastoma pathways and showed a significantly lower frequency of level 1 actionable alterations according to OncoKB. CONCLUSIONS: Loss of ER and/or PR may identify a distinct evolutionary trajectory of ER+/HER2- metastatic progression, largely non-overlapping with ESR1-mutant endocrine resistance. Further studies on matched primary and metastatic samples are warranted.

Humans↗
PubMed2026

Competing subclones and fitness diversity shape tumor evolution across cancer types.

MOTIVATION: Intratumor heterogeneity arises from ongoing somatic evolution and complicates cancer diagnosis, prognosis, and treatment. Reconstructing evolutionary dynamics typically requires spatiotemporal samples, which are often unavailable in clinical settings. Computational approaches that can infer tumor evolutionary history from single-timepoint bulk sequencing data remain limited. RESULTS: We present estimating evolutionary events through single-timepoint sequencing (TEATIME), a novel computational framework that models tumors as mixtures of two competing cell populations: an ancestral clone with baseline fitness and a derived subclone with elevated fitness. Using cross-sectional bulk sequencing data, TEATIME estimates mutation rates, timing of subclone emergence, relative fitness, and number of generations of growth. To quantify intratumor fitness asymmetries, we introduce a novel metric-fitness diversity-which captures the imbalance between competing cell populations and serves as a measure of functional intratumor heterogeneity. Applying TEATIME to 33 tumor types from The Cancer Genome Atlas, we revealed divergent as well as convergent evolutionary patterns. Notably, we found that immune-hot microenvironments constraint subclonal expansion and limit fitness diversity. Moreover, we detected temporal dependencies in mutation acquisition, where early driver mutations in ancestral clones epistatically shape the fitness landscape, predisposing specific subclones to selective advantages. These findings underscore the importance of intratumor competition and tumor-microenvironment interactions in shaping evolutionary trajectories, driving intratumor heterogeneity. Lastly, we demonstrate that TEATIME-derived evolutionary parameters and fitness diversity offer novel prognostic insights across multiple cancer types. AVAILABILITY AND IMPLEMENTATION: R implementation of TEATIME is available on GitHub (https://github.com/liliulab/TEATIME) and Zenodo (https://zenodo.org/records/17422174).

Neoplasms↗
PubMed2026

Measurable Residual Disease and the Unresolved Biology of Leukemic Stem Cells.

Measurable residual disease (MRD) testing has transformed the management of hematologic cancers by enabling detection of residual malignant cells after therapy. Current approaches rely on qPCR and next-generation sequencing to monitor leukemia-associated somatic mutations, while multiparameter flow cytometry identifies aberrant leukemic immunophenotypes. Although these methods provide valuable prognostic and therapeutic information, MRD negativity remains an imperfect surrogate for cure. Most MRD platforms evaluate CD45+, rapidly dividing leukemic populations and fail to detect quiescent cells that may survive cytotoxic therapies which efficiently target proliferating hematopoietic cells. Relapse frequently occurs despite deep molecular remission, suggesting persistence of rare leukemic stem cells (LSCs) that are intrinsically resistant to chemotherapy and targeted therapies. The paradox of relapse despite molecular remission could be explained by the presence of very small embryonic-like stem cells (VSELs) which are pluripotent, quiescent stem cells sitting at the top of cellular hierarchy in multiple adult tissues including bone marrow. A pluripotent VSEL divides through asymmetrical cell division to give rise to two cells of different sizes and fates, smaller cell is to self-renew while the bigger is lineage-restricted and tissue-committed progenitor which undergoes extensive epigenetic changes, divides rapidly and undergoes clonal expansion before further differentiation. Dysfunctions of VSELs initiate both solid and hematologic cancers. Based on this view, somatic mutations monitored during MRD assessment possibly represent downstream consequences of clonal expansion rather than the initiating drivers of disease persistence. Thus, exclusive monitoring of somatic mutations and CD45 + leukemic populations possibly overlook rare, small-sized, CD45- VSELs that contribute to therapeutic resistance and relapse.

Humans↗
PubMed2005

The neglected epidemic: road traffic accidents in a developing country, State of Qatar.

The objective of the study is to explore the pattern of road traffic accidents (RTA) and their causes in the State of Qatar. A total of 52,160 RTA, 1130 injuries and 85 fatalities were registered during the year 2000. The data on RTA, injuries and fatalities was obtained from the Traffic Department of the Ministry of Interior, Supreme Council for Planning and Ministry of Public Health. The major cause of traffic accidents in Qatar was careless driving (71%). Relatively there was a more rapid increase in the number of registered vehicles (155%), but accidents were only (61%) in 2000 compared to the year 1983. The majority of victims (53%) were in the age group (10-40) "the most productive class in Society". Forty-three per cent of the total drivers who died due to RTA were in the age group (10-19) who were unlicensed drivers. In 2000, deaths due to RTA were the third leading cause of death after the diseases of the circulatory system and cancer. In conclusion, it is possible to control the epidemic of road traffic injuries through strict policy interventions, mass media and a national traffic campaign to increase the use of seat belts.

Accidents, Traffic↗
PubMed2026

Pediatric sarcomas: challenges and opportunities.

Pediatric sarcomas are a heterogeneous group of rare mesodermal malignancies. These cancers, which affect children from infancy through adolescence and young adulthood, are in general challenging to treat with currently available therapies. Biologically, many are characterized by quiet genomes, fusion oncoproteins, immune "cold" microenvironments, and vast epigenetic deregulation that contributes to diverse and complex mechanistic drivers. Multifaceted advancements in research strategies, including high-throughput screening, new model systems, surfaceome profiling, and study of oncogenic fusion condensates have led to new opportunities for understanding the biology of pediatric sarcomas. To continue to make progress for these difficult to treat cancers, it will be critical to continue to improve access to bioinformatic data, approach patient care using innovative clinical trial frameworks, and foster interdisciplinary partnerships among medicinal chemists, scientists, clinicians, advocates, and industry partners.

Humans↗