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Case-control study of hair dye use by patients with breast cancer and endometrial cancer.

A case-control study was undertaken of use of permanent and semipermanent hair dyes by women with cancers of several sites, including breast and endometrium. In London, Ontario, 50 cases of of breast cancer and in Toronto 35 cases of breast cancer and 36 cases of endometrial cancer were identified in cancer treatment centers. In London, controls were selected from hospitalized women with diseases other than cancer; in Toronto, controls were selected from women living in the same neighborhood as the patients with cancer. The results did not suggest an increased risk of either breast or endometrial cancer in users of permanent or permanent and semipermanent dyes combined. Although the numbers of cases and controls were small, the consistency of the results for both sites, in both study centers, and the absence of any clear positive relationship between various measures of intensity of use and risk of cancer provided evidence that a large increase in risk was not missed.

Adult

The Association of Diabetes-Related Dietary Patterns with Pancreatic Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study.

BACKGROUND: Pancreatic cancer is relatively rare but remains one of the most lethal tumors. Identifying modifiable risk factors is a crucial step to reduce disease burden. Evidence suggests a potential role of type 2 diabetes mellitus in its pathogenesis. OBJECTIVES: The objective of this study is to examine the association between dietary patterns related to diabetes and pancreatic cancer risk in a European population. METHODS: A total of 367,395 participants from the European Prospective Investigation into Cancer and Nutrition study were included. After a median follow-up of 14.9 y, 926 incident cases were identified. The Diabetes Risk Reduction Diet (DRRD), the Empirical Dietary Index for Hyperinsulinemia (EDIH), and the Empirical Dietary Index for Insulin Resistance (EDIR) were estimated from food frequency questionnaires at recruitment. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between dietary patterns and pancreatic cancer were calculated using multivariable Cox proportional hazards regression models, adjusted for relevant confounders. RESULTS: Adherence to DRRD showed no association with risk of pancreatic cancer (HRT3vsT1: 0.94; 95% CI: 0.79, 1.12). Higher adherence to EDIH was associated with a borderline 19% increased pancreatic cancer risk (HRT3vsT1: 1.19; 95% CI: 0.99, 1.44). No significant associations were observed in relation to EDIR. No heterogeneity was observed among the subgroups. CONCLUSIONS: Higher adherence to a hyperinsulinemic dietary pattern may contribute to risk of developing pancreatic cancer in our population. Further research is warranted to elucidate the potential role of dietary factors in cancer risk prevention.

Humans

The combined approach to cancer therapy in cancer centres.

In the complex field of cancer therapy the cancer centre approach may be seen more clearly by division of its structure into vertical and horizontal components. Vertically, there are numerous special consultative clinics in types of cancer usually associated with a body region (lung, breast, melanoma, etc.). Horizontally, there are teams of specialists (surgeons, radiotherapists, solid tumour chemotherapists), in some clinics supplemented by haematologists, immunologists, and endocrinologists, providing a wide therapeutic spectrum. Working together in a particular consultative team, the specialists are clinical oncologists, but without the summed wisdom and expertise of the group, the members are more accurately designated individually as specialists in the field from which they spring, for example, thoracic surgeon, haematologist, radiotherapist, and so on. The team approach lends itself to full exploitation of all the centralized sophisticated cancer machinery, be it in the form of equipment like cell-trifuges and linear accelerators, a range and depth of cancer monitoring aids, or a medical record system aligned to a computer, with consequent immediate and long-term therapeutic gain to patients. For the State there is greater efficiency and hence economy. In teaching, the aggregation of all matters relating to cancer therapy presents enhanced opportunities for training of technicians and scientists and nurses as well as doctors, for postgraduate instruction, and for continuing education. For progress in understanding cancer, it is clear that clinical research in conjunction with the combined approach in cancer centres can be conducted with sufficient numbers of patients to give statistical credence to clinical trials.

Antineoplastic Agents

Genetic mechanisms in cancer predisposition: report of a cancer family.

A family is described in which four children developed cancer affecting different organs:lymphoma, meningeal sarcoma, osteogenic sarcoma, and adenocarcinoma of the cecum. Since there was only one other case of cancer in previous generations of this family, an hypothesis is put forth to explain this unusual aggregation on the basis of recombination of common genes. It is postulated that each parent carried a different combination of genes which, though not associated with increased cancer predisposition in the combinations in which they were present in the parents, due to independent assortment resulted in a combination producing cancer susceptibility in half of the offspring. Such genetic loci could include factors similar to an oncogene which is normally held in control by genes at another locus; thus the dominant oncogene without the dominant controlling genes would make for cancer susceptibility, while the controlling genes without the oncogene would be associated with cancer resistance since two mutations would then be required for malignant development. To explain the occurrence of lymphoma in one of the children in this family, a third set of genes is included in this model--genes affecting immunocompetence, in which the normal allele is dominant. This three locus model has the advantage of being able to explain not only the occasional cancer family, but also the distribution of cancer susceptibility and resistance in the general population.

Adenocarcinoma

Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients: interview study from the Third National Cancer Survey.

From personal interviews obtained for 7,518 incident cases of invasive cancer from the population-based Third National Cancer Survey, the quantitative lifetime use of cigarettes, cigars, pipes, unsmoked tobacco, wine, beer, hard liquor, and combined alcohol were recorded, as well as education and family income level. In an initial screening analysis of these data, Mantel-Haenszel 2 X 2 contingency tabulations and multiple regression analyses were used to compare each specific cancer site with controls from other sites to test for associations with the "exposure variables." Significant positive associations with cigarette smoking were found for cancers of the lung, larynx, oral cavity, esophagus, stomach, pancreas, bladder, kidney, and uterine cervix. Other forms of tobacco were associated with cancers of the oral cavity, larynx, lung, and cervix. Consumption of wine, beer, hard liquor, and all combined showed positive associations with neoplasms of the oral cavity larynx, esophagus, colon, rectum, breast, and thyroid gland. College educaton and high income both showed positive associations with cancers of the breast, thyroid gland, uterine corpus, and melanomas in males. These same indicators of high socioeconomic status showed inverse associations with invasive neoplasms of the uterine cervix, lung, lip-tongue, and colon in females. College attendance (but not income) showed an inverse association with stomach cancer and positive association with pancreatic cancer in males. Still other tumor sties showed "suggestive" associations with each of these exposure variables. In the analyses producing these results, age, race, sex, smoking, drinking, education, income, parity, foreign birth, marital status, and geographic location were used as stratification variables separately or in combination when appropriate to assess and control for their potentially confounding affects and to examine results in different strata to assess interaction.

Adult

Cancer incidence by marital status: U.S. Third National Cancer Survey.

Site-specific cancer incidence rates were computed by sex, age, and marital status for whites and blacks separately for ages 35-64 years with the use of population-based incidence data from the Third National Cancer Survey (1969-71) and with demographic data from the 1970 U.S. Census. Although rates were presented for all cancer sites combined and for 44 specific sites or rubrics, discussion focused on the 17 most common cancers. Within age, race, and sex groups, patterns of cancer incidence by marital status were compared by means of standardized incidence ratios, and the consistency of marital status patterns across age groups was assessed statistically. Among the most notable findings were: excess cancer rates across most sites and age groups in single black males, consistently high rates for cancer of the lung and bronchus in divorced white males and in single black females, low rates for the hormone-dependent reproductive tumors (prostate gland, breast, uterine corpus, and ovary) in separated white males and females, and high rates for cervical cancer among separated white women. Marital status patterns, where found, frequently differed between whites and blacks and between males and females.

Adult

The lipid-chemical features of the metastatic tissues into the liver from the human gastric cancer, large intestinal cancer and malignant insulinoma.

In order to clarify the biochemical features of metastatic tissues into the liver of human cancerous cells, 12 of primary cancerous tissues and 3 of metastatic tissues of the large intestinal cancer, 6 of primary cancerous tissues and 2 of metastatic tissues of the gastric cancer, and 3 of primary cancerous tissues and 3 of metastatic tissues of malignant insulinoma were studied lipid-chemically. Cancerous tissues and metastatic tissues into the liver were collected by biopsy or surgical operation. From each tissue, the total lipid was extracted and one part of the total lipid was separated into phospholipid and triglyceride by TLC. Then, the fatty acid composition and the fatty acid content of each lipid fraction were measured by GLC. The most remarkable findings were recognized in the phospholipid fatty acid composition of the tissues. Namely, the percentage values of C14:0 and C16:1 were larger and that of C20:4 was smaller in metastatic tissues than those of gastric primary lesions. As for the large intestinal cancer, the percentage value of C18:1 was smaller and that of C18:2 larger in metastatic tissues than those of primary lesions. In the malignant insulinoma, the percentage value of C18:0 was larger in metastatic tissues than that of the primary lesions.

Adenoma, Islet Cell

Environmental cancer: on the causes of the main human cancers.

A brief review is given of the causes of the main human cancers. We distinguish occupationally-incurred cancer, which arises in individuals exposed at work to varied carcinogenic chemicals and which yielded cancer at a site depending on the nautre of the carcinogen. In the context of the total incidence of cancer in the United States, occupational cancer assumes a minor quantitative role. Nonetheless, provided proper plant design and hygienic measures are developed, these cancers are totally preventable. Most of the remaining human cancers in the United States such as cancer of the respiratory tract, the digestive tract including stomach and large bowel, and in the endocrine-sensitive organs like breast, prostate, ovary, and endometrium are related to our lifestyle, namely smoking of cigarettes, and diet. The mechanism whereby lifestyle translates to certain of these diseases is presented, and recommendations for prevention are made. Considering the increasing cost of health care, it is noted that prevention is not only ethically best, but economically sound.

Breast Neoplasms

[Who needs more psychosocial oriented rehabilitation -- women after breast cancer or women after genital cancer? -- A sociopsychological study of 308 women (author's transl)].

A standardised questionnaire and personality test were used to study whether women after breast cancer treatment, or women treated for genital cancer need psychosocial counselling more frequently. The interview was given to 308 women during the author's tumor after-care consultations. 1. Repercussion on their marital lives were reported three times more often by women treated for genital cancer than by women after mastectomy (p less than 0.01). There was not significant difference with regard to their family status. 2. As epidemiologically expected -- mastectomy patients had born less children than women treated for genital cancer (p less than 0.05). 3. A reduced self-confidence was reported more often by patients treated for breast cancer than by the other patient group (p less than 0.01). 4. No decrease in working performance was observed by 50% of the women treated for genital cancers as against one third of the masectomy patients. 5. Work resumption was reported more often to be strenuous for masectomy patients than for women treated for genital cancer (p less than 0.05). 6. Woman after mastectomy experiences 50% less sexual repercussions than genital cancer patients (p less than 0.05).

Breast Neoplasms

Subclonal Complete Loss of CDKN1B as a Common Genomic Alteration in Prostate Cancer: Associations With Race and Prostate Cancer Outcomes.

Homozygous biallelic inactivation of CDKN1B is thought to be rare in cancer, including prostate cancer. In the present study, we report that the prevalence of subclonal genomic loss of CDKN1B, especially among self-reported African-American or Black (AA) individuals, has likely been underestimated in primary prostate cancer. Using immunohistochemistry (IHC) for p27 protein and a large cohort of whole tissue sections from radical prostatectomy (N = 412) from AA and European American (EA) individuals, we discovered an unexpectedly high frequency of regions of intratumoral complete p27 protein loss (IPPL) within larger tumor nodules that otherwise showed intact p27 staining that was more prevalent among prostate cancer in AA individuals (18.1%) than EA individuals (12.2%). Regions of IPPL were tightly associated with loss of CDKN1B messenger RNA by in situ hybridization. Furthermore, these focal regions of IPPL were closely linked to CDKN1B genomic loss as detected by next-generation sequencing panel sequencing of laser-captured regions. The detection of IPPL by IHC was associated with ≥pT3 pathologic stage (extraprostatic extension and seminal vesicle involvement) and pN1 (local lymph node involvement) disease; however, when stratified by race, these associations were only significant among AA participants. IPPL was further associated in both univariate and multivariate analyses with the development of biochemical recurrence and metastasis after primary treatment, specifically in AA individuals. The prevalence of p27 genomic alterations in metastatic disease is higher than that of primary prostate cancer in publicly available data sets as well as in our analysis of autopsy specimens via IHC. Overall, subclonal biallelic loss of CDKN1B resulting in complete p27 protein loss is one of the most commonly occurring biallelic tumor suppressor genomic alterations in primary prostate cancer and could contribute to worse prostate cancer outcomes, specifically in AA individuals. Our findings warrant further exploration into the clinical utility of using IHC for p27 loss as a prognostic biomarker.

CDKN1B cancer disparities

Repair of DNA double-strand breaks after low radiation doses in childhood cancer survivors and matched cancer-free individuals.

DNA double-strand breaks (DSBs) which arise in G1- or G0-phase normal human cells are repaired by nonhomologous end-joining (NHEJ), a pathway which is important for cell survival but can cause mutations at the break sites. DSB repair by NHEJ is very efficient at high damage levels of 1 or more DSBs per cell, much less efficient at lower damage levels and almost absent if only ~0.05 DSBs per cell are induced. Here, we have analyzed the repair of high and low levels of radiation-induced DSBs in primary fibroblasts from 136 childhood cancer survivors, half of whom developed a second independent tumor later in life, and compared it to the response of primary fibroblasts from 68 individually matched cancer-free individuals. We measured the DSB repair efficiency by quantifying residual γH2AX foci with an automated scoring system at 24 h after irradiation with doses of 2.5, 5, 10, and 100 mGy, which induce about 0.0625, 0.125, 0.25, and 2.5 DSBs per cell, respectively. Although childhood cancer survivors and cancer-free individuals repaired DSBs after 10 and 100 mGy equally efficiently, their response to lower doses differed drastically. While repair in cancer-free individuals was inefficient after 2.5 mGy, childhood cancer survivors repaired DSBs after this dose as efficiently as after higher doses. These results indicate that most of the childhood cancer survivors analyzed here may harbor a genetic alteration that affects their response to low levels of DSBs. We suggest that such alterations may be either inherited or caused by previous tumor treatments.

Humans

Pan-cancer characterization of HMGA1 reveals its oncogenic role in tumor microenvironment and stemness: functional validation in pancreatic cancer migration and invasion.

BACKGROUND: HMGA1 is a chromatin-associated oncogenic factor implicated in tumor progression, epithelial-mesenchymal transition (EMT), stemness, and metastasis. However, its pan-cancer expression and prognostic patterns, epigenetic activation, and relationship with malignant-cell stemness/plasticity and tumor microenvironment (TME) remodeling in pancreatic adenocarcinoma (PAAD) remain incompletely defined. This study aimed to systematically characterize HMGA1 across cancers and clarify its clinical and biological relevance in PAAD. METHODS: Pan-cancer transcriptomic, clinical, genetic, methylation, immune, and stemness data were integrated from multiple public databases. PAAD single-cell RNA sequencing data were analyzed to localize HMGA1 expression, infer malignant-cell pseudotime, calculate a stemness module score, and assess ligand-receptor communication using CellChat. Public HMGA1-knockdown RNA sequencing data were reanalyzed to evaluate transcriptional remodeling. The Cancer Genome Atlas (TCGA)-PAAD expression and methylation data were used to assess TME-remodeling, immune-suppression, stemness/plasticity, cytokine/chemokine, checkpoint, and promoter-methylation features. HMGA1 expression and function were further examined using immunohistochemistry (IHC), quantitative real-time polymerase chain reaction, Western blotting, wound-healing assays, and Transwell migration and invasion assays. RESULTS: HMGA1 was upregulated in most tumor types, and high expression was associated with unfavorable survival in multiple cancers, including PAAD. In PAAD, HMGA1 was enriched in malignant epithelial cells and positively correlated with pseudotime (Spearman's rho =0.594), while the stemness module score increased along pseudotime (rho =0.748). HMGA1-high malignant cells showed markedly stronger CellChat-inferred outgoing communication, predominantly involving extracellular matrix (ECM)-receptor, adhesion-related, and selected immunomodulatory ligand-receptor axes. HMGA1 knockdown was associated with broad remodeling of EMT, TGF-β, Hedgehog, IL6/JAK/STAT3, KRAS, and cancer stem cell/stemness-related programs rather than uniform suppression of these programs. HMGA1 promoter methylation was inversely correlated with HMGA1 expression (rho =-0.633) and the TME-remodeling score (rho =-0.347). HMGA1 was associated with selected mediators, including PPIA, PLAU, ANXA1, LGALS9, TGFB1, CD276, and CD47, but not with a generalized checkpoint-high phenotype. Functionally, HMGA1 knockdown significantly reduced pancreatic cancer (PC) cell migration and invasion. CONCLUSIONS: These findings support an association-based model in which promoter hypomethylation-associated HMGA1 activation is linked to malignant epithelial stemness/plasticity, ECM/adhesion-dominant TME remodeling, selected immunomodulatory programs, and aggressive PAAD phenotypes. Further mechanistic and clinical validation is required before HMGA1 can be used for therapeutic stratification or immunotherapy-response prediction.

HMGA1

A Qualitative Analysis of Cancer Survivors' Experience in a Time-Restricted Eating vs Control Clinical Trial to Address Cancer-Related Fatigue.

PURPOSE: To describe cancer survivors' lived experiences in a clinical trial that tested an individualized nutrition counseling with or without time-restricted eating to address cancer-related fatigue. METHODS: The Fatigue REDuction After cancer study was a two-arm, randomized controlled trial. Participants were adult cancer survivors who were 2 months to 2 years post-treatment. All participants received individualized nutrition counseling; those in the time-restricted eating group self-selected a consistent 10-hour eating window for 12 weeks. After the study, semi-structured exit interviews were conducted to gauge participants' experiences in the trial. Interviews were transcribed and two independent coders thematically analyzed the interviews using inductive and deductive coding. NVivo software was used for data organization and analysis. RESULTS: Participants (n = 24; TRE = 11; Control = 13) were 55 ± 13 years old, 75% were female, and they had a variety of cancer types. The majority of participants found that being in the study helped them to set and achieve lifestyle goals and would therefore recommend the study to others. Participants in the time-restricted eating group noted that time-restricted eating helped them set a better routine, providing a positive sense of control. However, some noted difficulty switching to a 14-hour fasting schedule, as it can interfere with their regular routine or employment schedules. Many participants noted they were happy that cancer-related fatigue was gaining more attention, hoping to find solutions for persistent cancer-related fatigue. CONCLUSION: The majority of participants found the study useful and, regardless of their group assignment or the intervention's impact on their fatigue, found the study helped them to gain better control of their dietary habits.

Humans

Intraperitoneal free cancer cells and their viability in gastric cancer.

Free cancer cells in the peritoneal cavity of 100 patients with gastric cancer were examined by means of Douglas lavage, and their viability was estimated by 3H-thymidine uptake with autoradiographical technic. Furthermore, the effect of mitomycin-C on the viability of free cancer cells in the peritoneal cavity was studied. The appearance of intraperitoneal free cancer cells was dependent on the degree of invasion of cancer to the gastric serosa; that is, free cancer cells were not found in cases without serosal invasion, but were found in 48% with serosal invasion. The viability of free cancer cells in the peritoneal cavity was relatively high, but could be suppressed remarkably by intraperitoneal administration of 10 mg of mitomycin-C.

Ascitic Fluid

Genital cancer in wives of penile cancer patients.

We identified the wives or ex-wives of 227 males of the 256 reported with cancer of the penis to the New York State Cancer Registry from Upstate New York from 1960-64. Utilizing the Registry, death certificates, hospital and physician records, we ascertained those wives who developed cancer at any site from 1951-1975. We generated expected numbers of cases of cancer at each site by applying the age specific incidence rates experienced by women of a specific age in a specific year designated by the age of the wife of the index case in each year, estimating withdrawals from age-specific death rates. Thus, our expected numbers are based on the experience of the women in Upstate New York with traits like those of spouses of the men in the same population with cancer of the penis. We found significantly more cases of cancer of the cervix than expected. This was not true for other sites of cancer.

Adult

Calcitonin heterogeneity in lung cancer and medullary thyroid cancer.

An investigation was made of the increased serum calcitonin in patients with medullary thyroid cancer and bronchogenic carcinoma in order to determine whether these conditions can be differentiated immunochemically. Exdogenous fractions of immunoreactive calcitonin were separated by gel filtration and radioimmunoassayed with calcitonin antibodies having different region specificities. The pattern of serum heterogeneity of patients with medullary thyroid cancer was characterized by the presence of at least seven different fractions of immunoreactive calcitonin, ranging from fraction I (greater than or equal to 30 000 molecular weight (MW) to fraction V (approximately 2500 MW). In contrast, most patients with bronchogenic cancer had a predominance of high MW fractions (i.e. fractions I and IIA). Following in vitro incubation of the serum, the typical MW pattern of bronchogenic cancer serum could be converted to the more diffuse pattern seen in the serum of medullary thyroid cancer. We were able to differentiate, pre-operatively, the hypercalcitonaemia serum of medullary thyroid cancer patients from that of bronchogenic cancer patients by determination of the ratio of calcitonin as radioimmunoassayed with midportion versus carboxyl terminal antibody.

Calcitonin

The Function of PPARα in Cancer Drug Development: A Promising Target for Cancer Treatment.

Cancer is one of the leading causes of mortality globally. PPAR modulators may hold great potential for the management of cancer patients. PPAR modulators also activate specific transcriptional pathways, regulate immune responses and inflammation, and influence the proliferation of various cancer cell types. In the last decade, emerging evidence has shown that PPARα, a nuclear hormone receptor, can modulate carcinogenesis via exerting effects on one or several characteristic pathological behaviors of cancer. This review summarizes current knowledge of PPARα function in various aspects of cancer development and the modulators that regulate PPARα. Based on the current knowledge, we have discussed the development of a potential modulator targeting PPARα for cancer treatment.

Humans

Liquid Biopsy Differentiation of Pancreatic Cancer From Non-Cancerous Pancreatic Disease Using Dielectrophoresis-Recovered Nanoparticles Carrying Cell-Free DNA and Protein Biomarkers.

Cancer-derived extracellular vesicle (EV) nanoparticles carry important biomarkers but are difficult to recover from plasma, making EV-based diagnostics a challenge for clinical settings. Here, we demonstrate nanoparticle-based detection of pancreatic cancer using dielectrophoresis (DEP) nanoparticle recovery technology, which purifies nanoparticles from undiluted plasma and quantifies associated biomarkers. We combined both nanoparticle recovery and biomarker quantification on a single device by simultaneously collecting cell-free DNA nanoparticles and EVs followed by on-chip biomarker fluorescent staining for DNA and Glypican-1. Using a blinded cohort, these biomarkers differentiated pancreatic cancer from benign pancreatic diseases, including cysts, pancreatitis, and precancerous low-grade intraductal papillary mucinous neoplasm (IPMN) lesions, with a sensitivity of 0.92, a specificity of 0.83, and an AUC of 0.93. The AUC increased to 0.97 for patients over 50 years old. This is higher than the standard invasive endoscopic ultrasound-guided fine needle aspiration tissue biopsy procedure (AUC 0.79). This study is among the first demonstrating a combined threshold of DNA and protein levels that can distinguish pancreatic cancer from its precursor IPMN lesions. We also demonstrated the detection of early-stage pancreatic cancer and high-grade in situ precancerous lesions. This DEP-based technique shows that multiple types of cancer-derived nanoparticles can be quickly and easily recovered from plasma making it promising for future clinical diagnostics.

Humans