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PubMed2003

Patterns of postmenopausal progestin use with estrogen in relation to endometrial cancer (United States).

OBJECTIVE: To investigate the risk of endometrial cancer associated with various regimens of postmenopausal hormone therapy. METHODS: Data from a population-based case-control study were analysed that included 591 women newly diagnosed with endometrial cancer, aged 40-79, and who were reported to Wisconsin's statewide tumor registry in 1991-1994. Similarly aged population controls (n = 2045) were randomly selected from lists of licensed drivers and Medicare beneficiaries. Information on hormone use and other factors was obtained through telephone interviews. RESULTS: Ever use of estrogen-progestin hormones was associated with increased endometrial cancer compared to women who had never used hormones; the increase per year of use was 7% (95% confidence interval 1-13%). Both cyclic (<10 days per month) and continuous progestin used with estrogen were associated with comparable twofold increases in risk relative to non-users. There was no increased risk associated with progestin used for 10-21 days per month. CONCLUSIONS: Both continuous and cyclic progestin regimens are associated with a much lower risk of endometrial cancer than estrogen alone. However, many women using these regimens remain at significantly increased risk of endometrial cancer.

Adult↗

PubMed1998

Identification of 12p as a region of frequent deletion in advanced prostate cancer.

The identification of homozygous deletions in malignant tissue has been a powerful tool for the localization of tumor suppressor genes. Representational difference analysis (RDA) uses selective hybridization and the PCR to isolate regions of chromosomal loss and has facilitated the identification of tumor suppressor genes such as BRCA2 and PTEN. Twenty RDA clones were generated by comparing genomic DNA from a prostate cancer xenograft to the same patient's normal kidney DNA. Southern blot analysis of the tester and driver and of normal and xenograft DNA, using the differential products as probes, showed the homozygous deletion in 16 of 20 RDA clones. The sequence of one of the differential products overlapped HSU59962, a genomic GenBank sequence on chromosome 12p12-13. Multiplex PCR of the xenograft DNA using polymorphic repeats mapped the deletion to a 1-5-cM region on 12p. Genomic DNA isolated from a panel of cryostat microdissected metastatic prostate adenocarcinomas/normal pairs was screened for loss of heterozygosity using the same polymorphic repeats. Loss of heterozygosity was demonstrated in 9 (47%) of 19 patients. This region may contain, or lie in close proximity to, tumor suppressor genes important in the progression and/or initiation of prostate cancer.

Adenocarcinoma↗

PubMed2026

PGC1α expression using targeted redox-responsive nanogels protects against prostate cancer in vivo.

Prostate cancer is among the most frequently diagnosed cancers in men in the UK and US. Increasing evidence implicates metabolic dysregulation as a critical driver of disease progression. Central to this process is peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) that promotes oxidative metabolism and mitochondrial biogenesis while inhibiting metastatic programs. This work investigated the therapeutic potential of PGC1α overexpression via mRNA delivery. Here, we report a prostate-specific, targeted disulphide-crosslinked nanogel system for intracellular delivery of mRNA encoding the N-terminal isoform of PGC1α (NT-PGC1α). Functionalization of the NGs with a peptide targeting prostate-specific membrane antigen (PSMA) enabled selective delivery of NT-PGC1α mRNA in PCa cells and 3D spheroid models. We confirmed sustained PGC1α expression, and increased mitochondrial protein content, indicative of enhanced mitochondrial biogenesis. These nanogels, which were prepared in situ using a nanopolymerization technique, exhibited high mRNA loading capacity, low cytotoxicity, and redox-responsive cargo release, enabling controlled cytosolic delivery following intracellular glutathione-mediated degradation. In vivo, systemic administration of the PSMA-targeted NT-PGC1α mRNA-loaded nanogels resulted in tumor-preferential accumulation and significant suppression of xenograft growth (by 73.4% relative to untreated control), with minimal systemic toxicity. This study presents the first example of a prostate-targeted, disulfide-crosslinked nanogel system for mRNA-mediated metabolic reprogramming in prostate cancer, and highlights its promise as a platform for future RNA-based targeted and precision stimuli-responsive cancer therapies.

Male↗

PubMedDate not supplied

Oral transmucosal fentanyl citrate in the outpatient management of severe cancer pain crises: a retrospective case series.

OBJECTIVE: This retrospective chart review evaluated the efficacy of oral transmucosal fentanyl citrate (OTFC) in an outpatient cancer pain center for patients experiencing severe exacerbations of pain that exceed usual breakthrough pain levels. PATIENTS: Records were reviewed for all patients who received OTFC at M.D. Anderson's outpatient pain clinic over a three-month time period. OTFC was used in thirty-nine patients experiencing a recent onset of severe pain (> or =7 on a 0-10 scale). All patients had cancer, cancer-related pain syndromes, and were opioid tolerant with an oral morphine equivalent daily dosage (MEDD) of (> or =40 mg/day. RESULTS: Prior to OTFC treatment, all patients reported a mean pain intensity of 9.0 (SD = 1.2). After OTFC treatment, patients reported a mean intensity of 3.0 (SD = 1.4), a significant reduction in pain intensity (P < 0.001). In most cases, OTFC averted the need for an emergency center visit, parenteral opioids, and hospital admission, which suggests that OTFC may be an effective alternative over intravenous opioids to rapidly titrate analgesia in selected opioid-tolerant cancer patients experiencing severe pain.

Administration, Oral↗

PubMed1984

Immunohistochemical detection of Ca antigen in normal, dysplastic and neoplastic squamous epithelia of the human uterine cervix.

Immunohistochemical staining was performed on biopsies and cytological samples from normal, dysplastic and neoplastic squamous epithelia using the monoclonal Ca 1 antibody. The results of staining 92 biopsies and 20 cytological samples are described and it is reported that positive staining with Ca 1 antibody was detected in normal, dysplastic and neoplastic epithelia. The role of the Ca 1 antibody in the study of cervical cancer is discussed.

Antibodies, Monoclonal↗

PubMed1995

[A case-control study on the risk factors of lung cancer in Guangdong].

A case-control study on interaction among the risk factors of primary lung cancer with 390 matched pairs was carried out in Guangdong from 1990 to 1993. The subjects of study were the in-patients with primary lung cancer (age 32-78), which consisted of 171 cases of primary lung squamous cell cancer (L. S), 138 cases of primary lung adenocarcinoma (L. A), and 81 cases of other pathological type (L. S:L. A = 1:0.8). Primary lung squamous cell cancer accounted for the majority (51.55%) of 291 male cases (L. S:L. A = 1:0.5). Primary lung adenocarcinoma made up the majority (57.57%) of 99 female cases (L. S:L. A = 1:2.7). Single factor conditional logistic regression analysis showed that the occurrence of lung cancer was closely associated with history of chronic bronchitis, emphysema, pulmonary tuberculosis and other pulmonary diseases (OR = 2.9-3.6, chi 2 = 13.52-37.55, P < 0.01) other risk factors were smoking, passive smoking from spouse or in the working place and family history of tumour (OR = 2.7-3.6, chi 2 = 8.53-33.15, P < 0.01). Driver, taking oral contraceptive, liking pickles or salted fish and bad ventilation in kitchen could be the risk factors of lung cancer (OR = 1.3-3.0, chi 2 = 4.78-5.0, P < 0.05). Further multiple conditional logistic regression analysis turned out that history of chronic bronchitis, emphysema, pulmonary tuberculosis, smoking, family history of tumour, passive smoking from spouse or in the working place, liking pickles were the independent risk factors of lung cancer (OR = 1.7-3.5). In search of the interaction between lung cancer and the risk factors which included history of chronic bronchitis, emphysema, pulmonary tuberculosis, smoking and passive smoking, a loglinear model analysis was performed. The results revealed that there was significant interaction between two factors in one-stage analysis. Although the interaction existed between chronic bronchitis and tuberculosis, chronic bronchitis and smoking or passive smoking, tuberculosis and passive smoking in the meantime, it had not attained the level of significance among three or more factors (including the principal effect of lung cancer) in two-stage analysis (chi 2 = 1.31-2.27, P > 0.13), and therefore the interaction of the former was not affected by the effects of the latter as yet.

Adenocarcinoma↗

PubMed2000

Previous lung disease and lung cancer risk among women (United States).

OBJECTIVE: The association between previous lung diseases (PLD) and lung cancer risk has not been studied extensively. We conducted a registry-based case-control study to examine the relation between previous lung diseases and lung cancer among women in Missouri. METHODS: Incident cases (n = 676) were identified through the Missouri Cancer Registry for the period 1 January 1993 to 31 January 1994. Controls (n = 700) were selected through drivers' license files and Medicare files. RESULTS: Whether analyzing all respondents or in-person interviews only, elevated effect estimates were noted for several types of PLD. Elevated relative risk estimates were shown for chronic bronchitis (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.3), emphysema (OR = 2.7; 95% CI = 1.8-4.2), pneumonia (OR = 1.6; 95% CI = 1.2-2.0), and for all PLDs combined (OR = 1.5; 95% CI = 1.2-1.9). Analysis of only direct interviews did not show a substantial or consistent pattern of change in relative risk estimates. Because PLDs identified close to the time of cancer diagnosis could conceivably be misdiagnosed, resulting from early lung cancer symptoms, we evaluated the effects on risk estimates of a "latency exclusion" of up to three years. When these exclusions were taken into account, ORs remained statistically significantly elevated only for emphysema. CONCLUSION: When earlier epidemiologic findings and underlying biological and genetic factors are taken into account, an association between PLD and lung cancer is plausible.

Adult↗

PubMed2024

DGKH-mediated phosphatidic acid oncometabolism as a driver of self-renewal and therapy resistance in HCC.

BACKGROUND AND AIMS: HCC is characterized by metabolic pathway aberrations, which enable cancer cells to meet their energy demands and accelerate malignant progression. Identifying novel metabolic players governing therapy resistance and self-renewal in HCC is crucial, as these properties are likely responsible for tumor recurrence. APPROACH AND RESULTS: Clinical traits and RNA-seq of patients with HCC in The Cancer Genome Atlas were used for weighted gene coexpression network analysis, where 1 module was significantly correlated with advanced pathological stage and stem cell population maintenance. Further analysis of this module by integrating data obtained from HCC patient nonresponders to tyrosine kinase inhibitors identified 361 commonly deregulated genes. Intriguingly, these genes are significantly enriched in the intracellular signal transduction pathway, with diacylglycerol kinase eta (DGKH) ranked as the most enriched gene in poorly differentiated HCC tumors. Clinically, DGKH was elevated in tumor tissues compared to nontumor tissues. Patients with higher DGKH expression exhibited a more undifferentiated state and were less responsive to tyrosine kinase inhibitors. Functional assays using DGKH-manipulated HCC cell lines demonstrated that DGKH augmented aggressive features, including cancer stemness, therapy resistance, and metastasis. Upstream of DGKH , we discovered that the E1A-associated protein p300 (EP300) binds to DGKH's promoter region, thereby increasing its transcriptomic expression. Mechanistically, DGKH promotes mTOR signaling by producing phosphatidic acid. In an immunocompetent mouse model, cotreatment with sorafenib and liver-directed AAV8-mediated Dgkh depletion significantly reduced tumor burden, self-renewal, phosphatidic acid production, and mTOR signaling. CONCLUSIONS: Our research demonstrated that DGKH is a crucial oncometabolic regulator of cancer stemness and therapy resistance, suggesting that inhibiting DGKH may lead to more effective HCC treatment.

Humans↗

PubMed2005

Occupation and risk of pancreatic cancer: a population-based case-control study in iowa.

OBJECTIVE: Previous epidemiological studies have inconsistently linked various occupations and industries to pancreatic cancer risk. METHODS: We analyzed data from a population-based case-control study conducted in Iowa involving 376 histologically confirmed incident pancreatic cancer cases and 2434 control subjects. RESULTS: A significantly increased risk was observed among men who worked in the following industries: chemical and allied products, transportation, and elementary and secondary schools. Increased risks also were observed in men who were employed as truck drivers; railroad brake, signal, and switch operators; purchasing agents and buyers; teachers; insurance agents; and retail supervisors. Among women, a significantly increased risk of pancreatic cancer was found for employment in furniture and home furnishing stores, and a borderline significantly increased risk among textile sewing machine operators and tenders. CONCLUSIONS: Working in several occupations and industries was associated with an increased risk of pancreatic cancer in this study, and these associations warrant further investigation.

Adult↗

PubMed1995

Lifetime alcohol consumption and risk of breast cancer.

The relation of lifetime alcohol intake to risk of breast cancer in pre- and postmenopausal women was examined in a case-control study in western New York. Cases with incident primary histologically confirmed breast cancer diagnosed during the period 1986-1991 (n = 740) and controls, frequency age-matched women drawn from New York state driver's license records (age < 65 yrs) and from records of the Health Care Finance Administration (age > or = 65 yrs, n = 810), were interviewed regarding intake of wine, beer, and hard liquor 2, 10, and 20 years ago and at 16 years of age. Although women in this study had generally low intakes of alcohol, there was little evidence of increased risk of breast cancer with intake of alcohol at any of the time periods or with an index of total lifetime intake. There was a weak indication of an increase in risk with beer for intakes of at least one drink per day. This risk was evident for 2, 10, and 20 years ago but not at 16 years of age. In this group with relatively low intakes of alcohol, evidence was weak for an association of increased risk of breast cancer with intake of alcohol, with the possible exception of a weak association with beer intake.

Adolescent↗

PubMed1997

Clinical process cost analysis.

BACKGROUND: New systems of reimbursement are exerting enormous pressure on clinicians and hospitals to reduce costs. Using cheaper supplies or reducing the length of stay may be a satisfactory short-term solution, but the best strategy for long-term success is radical reduction of costs by reengineering the processes of care. However, few clinicians or institutions know the actual costs of medical care; nor do they understand, in detail, the activities involved in the delivery of care. Finally, there is no accepted method for linking the two. METHODS: Clinical process cost analysis begins with the construction of a detailed flow diagram incorporating each activity in the process of care. The cost of each activity is then calculated, and the two are linked. This technique was applied to Diagnosis Related Group 75 to analyze the real costs of the operative treatment of lung cancer at one institution. RESULTS: Total costs varied between $6,400 and $7,700. The major driver of costs was personnel time, which accounted for 55% of the total. Forty percent of the total cost was incurred in the operating room. The cost of care decreased progressively during hospitalization. CONCLUSIONS: Clinical process cost analysis provides detailed information about the costs and processes of care. The insights thus obtained may be used to reduce costs by reengineering the process.

Cost Control↗

PubMed2002

Use of anti-inflammatory and non-narcotic analgesic drugs and risk of non-Hodgkin's lymphoma (NHL) (United States).

OBJECTIVE: To examine whether exposures to anti-inflammatory and non-narcotic analgesic drugs are associated with risk of non-Hodgkin's lymphoma (NHL). METHODS: A case-control study was conducted among women living in upstate New York. The study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls randomly selected from the Medicare beneficiary files and New York State driver's license records. Information regarding use of common medications in the past 20 years and potential confounding variables was obtained by telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using an unconditional logistic regression model. RESULTS: There were non-significant increases in risk associated with ever use of cortisone injections and oral cortisone (OR = 1.44 (CI 0.98-2.11) for injections and 1.21 (CI 0.73-2.00) for oral cortisone, although there was no clear dose-response relationship with either type. On the other hand, the risk of NHL progressively increased with the frequency of use of non-steroidal anti-inflammatory and non-narcotic analgesic drugs (NSAID/NNAD) (p-value for trend 0.008). Women who used any of these medications daily for more than 10 years had an OR of 1.90 (CI 1.01-3.57), compared with those who used it less than once a month on average. The risk associated with long-term use was most pronounced for ibuprofen, intermediate for aspirin, and least for acetaminophen. CONCLUSIONS: Because the population-attributable risk associated with NSAID/NNAD use is potentially large, our results need to be verified in further epidemiologic studies.

Adult↗

PubMed2026

HDAC inhibition via suberoylanilide hydroxamic acid ameliorates doxorubicin-induced cardiotoxicity.

Anthracycline-induced cardiotoxicity remains a major limitation of cancer therapy, and effective preventive strategies are lacking. Topoisomerase IIb has been implicated as a central driver of this toxicity, suggesting that epigenetic regulators may interfere with the pathological cardiac response. Here, we show that doxorubicin promotes topoisomerase IIb accumulation at cardiomyocyte-specific gene promoters (e.g., Actc1, Myl2, and Myh7) overlapping myocyte enhancer factor 2 binding sites and enhances myocyte enhancer factor 2 -dependent transcription. This response is attenuated by the pan-histone deacetylase inhibitor suberoylanilide hydroxamic acid. Suberoylanilide hydroxamic acid -mediated cardioprotection requires class IIa histone deacetylases, as genetic loss of HDAC4 abolishes its effect. Mechanistically, suberoylanilide hydroxamic acid induces acetylation of the chaperone 14-3-3, disrupting its interaction with HDAC4/5, promoting their nuclear accumulation, and repressing myocyte enhancer factor 2 - driven transcription. In vivo, suberoylanilide hydroxamic acid mitigates doxorubicin-induced cardiotoxicity. These findings identify histone deacetylase inhibition as a cardioprotective repurposing strategy and reveal a mechanistic link between epigenetic regulation and anthracycline-associated cardiotoxicity.

Doxorubicin↗

PubMed1987

Occupation and lung cancer risk among New Jersey white males.

The association of occupation with lung cancer risk was examined in a case-control study conducted in six areas of New Jersey. The study included 763 white males with incident histologically confirmed primary cancer of the trachea, bronchus, and lung and 900 general population white male controls selected from driver's license and death certificate files. Altogether, 27 employment categories had a smoking-adjusted odds ratio (OR) of 1.3 or greater; five of these with significantly high OR contributed to an occupational population attributable risk of 13%. Masons and tilesetters; janitors and cleaners; printing workers; and trucking service, warehousing, and storage workers had significantly high risks overall and for longer durations of employment. Shipbuilding workers had significantly high risk overall and for short duration of employment. Although the excess risk for all shipbuilding workers was primarily among those with reported exposure to asbestos, the risk was also high among welders, burners, sheet metal workers, and boilermakers with no reported asbestos exposure.

Asbestos↗

PubMed2006

What are cyclooxygenases and lipoxygenases doing in the driver's seat of carcinogenesis?

Substantial evidence supports a functional role for cyclooxygenase- and lipoxygenase-catalyzed arachidonic and linoleic acid metabolism in cancer development. Genetic intervention studies firmly established cause-effect relations for cyclooxygenase-2, but cyclooxygenase-1 may also be involved. In addition, pharmacologic cyclooxygenase inhibition was found to suppress carcinogenesis in both experimental mouse models and several cancers in humans. Arachidonic acid-derived eicosanoid or linoleic acid-derived hydro[peroxy]fatty acid signaling are likely to be involved impacting fundamental biologic phenomena as diverse as cell growth, cell survival, angiogenesis, cell invasion, metastatic potential and immunomodulation. However, long chain unsaturated fatty acid oxidation reactions indicate antipodal functions of distinct lipoxygenase isoforms in carcinogenesis, i.e., the 5- and platelet-type 12-lipoxygenase exhibit procarcinogenic activities, while 15-lipoxygenase-1 and 15-lipoxygenase-2 may suppress carcinogenesis.

Animals↗

PubMed1991

Worksite health promotion in four Midwest cities.

A survey of worksite health promotion activities in nine areas of health was conducted in four Midwest cities--Winona and St. Cloud, MN; Eau Claire, WI and Sioux Falls, SD to determine how many worksites are involved in these activities; how many different kinds of programs they offer; and whether or not worksite involvement is growing in these areas of health. All worksites with over 100 employees were surveyed with a completion rate of 96% for eligible worksites. Comparing program offerings at worksites with such offerings by other community providers, we find worksites provide 40% of the total of such programs to adults. They tend to operate most programs independently of other community providers. Exercise and smoking cessation programs are most commonly offered. Worksites in the four communities significantly differed in the number of exercise program options offered and in the prevalence of worksite involvement in home, personal and drivers' safety programs. Compared to national survey results, worksites in these Midwest cities show a lower level of participation in heart disease and cancer screening activities. There is a high rate of dropout among current providers of heart disease screening activities and few nonproviders are initiating programs. Program initiation among nonproviders is highest in smoking cessation, weight loss and nutrition. Program growth among current providers is high in the areas of chemical dependency, exercise and personal, home and drivers' safety.

Data Collection↗

PubMed1997

Frequency of eating and risk of colorectal cancer in women.

Numerous dietary constituents have been extensively studied with regard to colorectal cancer risk, but food intake patterns have been studied less frequently. The purpose of these analyses was to describe associations between frequency of eating and colorectal cancer risk in women. Female Wisconsin residents aged 30-74 years with a diagnosis of colorectal cancer within two years were identified through the statewide tumor registry. Control subjects were randomly selected from lists of licensed drivers (< 65 yrs old) and Medicare beneficiaries (65-74 yrs old). Meal and snack frequency was obtained on a subset of case (n = 189) and control (n = 322) subjects. Odds ratios and 95% confidence intervals (CIs) obtained from conditional logistic regression models were used to estimate multivariate-adjusted relative risks. Compared with women consuming three or four meals daily, women consuming one to two meals daily had an adjusted relative risk of 0.57 (95% CI = 0.34-0.94). Snacking frequency and frequency of meals + snacks were not associated with cancer risk. These results are consistent with other reports and suggest that meal frequency is associated with colorectal cancer risk.

Adult↗

PubMed1995

Postmenopausal hormone use and risk of large-bowel cancer.

BACKGROUND: The epidemiology of large-bowel cancer suggests a role for endocrine factors in its development. Although analytic studies have not consistently provided evidence for an association between reproductive history and large-bowel cancer, some relatively small studies have observed a reduced risk among women using postmenopausal hormone replacement therapy (HRT). PURPOSE: This study was planned to evaluate more precisely the relationship between HRT and the risk of colon and rectal cancers. METHODS: Female residents of Wisconsin aged 30-74 years with a diagnosis of colon or rectal cancer within 2 years were identified through a statewide tumor registry. Control subjects were randomly selected from lists of licensed drivers if the case subjects were less than 65 years old and from lists of Medicare beneficiaries if they were 65-74 years old. Information on post-menopausal hormone replacement use, medical history, and family history was obtained in telephone interviews. After premenopausal women were excluded, 694 case subjects and 1622 control subjects remained for analysis. The odds ratios and 95% confidence intervals (CIs) obtained from conditional logistic regression models were used to estimate relative risks (RRs). All RRs were adjusted for age, family history of large-bowel cancer, use of screening sigmoidoscopy, and recent alcohol consumption. RESULTS: Compared with postmenopausal women who never used HRT, recent users had an RR of 0.54 (95% CI = 0.36-0.81) for colon cancer and an RR of 0.91 (95% CI = 0.54-1.55) for rectal cancer. This inverse association was observed among users of both estrogen only and combined estrogen and progestin preparations. Decreasing time since last use was inversely associated with colon cancer risk (P for trend < .001). The effect of HRT appeared to be stronger among women at lower absolute risk of colon cancer, particularly among women with lean body mass. CONCLUSIONS: Use of HRT was associated with a statistically significant reduced risk of colon cancer. In contrast, no statistically significant relationship was observed for rectal cancer. Given the widespread use of postmenopausal hormones and the morbidity and mortality from adenocarcinoma of the bowel in women, these findings may have potentially important public health implications.

Aged↗