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PubMed2025

Modeling and targeting general and chromosome-specific aneuploidy in cancer.

Throughout the last century, aneuploidy has been cemented as a hallmark of cancer. Although the association of aneuploidy with tumorigenesis has been well established, the role of these genetic imbalances in tumor formation has only recently begun to be elucidated. Advancements in genomics have revealed the complexity and context dependence of the effect of aneuploidy on cancer growth, while developments in genetic editing have allowed for proper modeling of specific aneuploidies. In this review, we discuss the key factors to consider when studying the role of aneuploidy in cancer and the tools that are available to do so. We then highlight recent studies that establish phenotypic contributions of aneuploidy to tumorigenicity. In particular, we highlight how general aneuploidy and chromosomal instability affect the tumor microenvironment and how specific chromosomal alterations, including the loss of chromosome 9p and the gain of chromosomes 8q and 1q, influence tumor behavior and therapeutic responses. Finally, we emphasize the potential of targeting aneuploidy-induced vulnerabilities to improve cancer treatment outcomes.

Aneuploidy↗
PubMed2003

Do women understand the odds? Risk perceptions and recall of risk information in women with a family history of breast cancer.

OBJECTIVES: To describe and compare women's risk perceptions and recall of breast cancer risk information in a cohort of first-time attendees at a family history clinic. METHODS: We conducted a 1-year prospective study of 158 women aged 18-45 years with a confirmed lifetime risk of breast cancer of 1 in 6 or greater. Risk perception and recall were assessed using a self-report questionnaire, completed pre-counselling and 3, 6, 9 and 12 months post-counselling, and through interviews conducted at 3 and 12 months. RESULTS: The proportion of women with accurate personal risk perceptions based on 'gambling' odds ('1 chance in x') significantly improved after risk counselling from 12% pre-counselling to 67% 3 months post-counselling (p < 0.001), which was maintained for 1 year. This was the method of reporting perceived risk associated with the best level of risk accuracy and the women's preferred format for describing risk, but the concept of lifetime risk was understood by only 44% of women. Qualitative risk categories ('high', moderate' or 'low') correlated significantly with women's self-reported odds values, but each category comprised a wide range of women's perceived numeric risks. Describing risk as the 'likelihood of breast cancer' resulted in a broad and somewhat inaccurate reporting of risk, compared with numeric ratings made at the same time. There was an increase of up to 4-fold in the proportion of women who failed to recall their risk value over time, and women were unable to accurately put the breast cancer risk in context compared with other health threats. CONCLUSIONS: All methods of describing risk have limitations, but the results of the present study provide good support for women's accurate recall of numeric risk values and their preference for use of these 'gambling' odds. This may have been influenced by consistency of the use of this method both in risk communication and in personal summary letters. Descriptive risk formats reflected higher levels of perceived vulnerability to breast cancer, and genetic counsellors need to be aware of these different perceptions.

Adolescent↗
PubMed2001

Women's interest in genetic testing for breast cancer susceptibility may be based on unrealistic expectations.

We report on results of an interview study assessing women's attitudes toward and hypothetical interest in genetic susceptibility testing for breast cancer. Data are from 246 interviews with women of varying ethnicity (African American, European American, Native American, and Ashkenazi Jewish), family history of breast cancer (negative, positive, and borderline), and educational level. Semistructured interviews included questions on general health beliefs; attitudes, experiences, and concerns about breast cancer; and hypothetical interest in genetic testing. Influence of specific test characteristics was assessed with 14 Likert scales varying negative and positive predictive value, timing of disease, possible medical interventions following a positive result. Results reported include both statistical and qualitative analysis. We found that women had a high level of interest in testing which, in general, did not vary by ethnicity, level of education, or family history. Interest in testing appeared to be shaped by an exaggerated sense of vulnerability to breast cancer, limited knowledge about genetic susceptibility testing, and generally positive views about information provided through medical screening. However, study participants were most interested in a test that didn't exist (high positive predictive value followed by effective, noninvasive, preventive therapy) and least interested in the test that does exist (less than certain positive predictive value, low negative predictive value, and limited, invasive, and objectionable therapeutic options). Our data suggest that without a careful counseling process, women could easily be motivated toward interest in a test which will not lead to the disease prevention they are seeking.

Attitude to Health↗
PubMed1984

Explaining participation in programmes for the early detection of breast cancer: a comparative analysis.

A trial to evaluate different methods for the early detection of breast cancer is being carried out in the United Kingdom. Its success depends, in part, upon achieving a high rate of participation. The study presented here examines and compares the health beliefs, health behaviour and socio-demographic characteristics of attenders and non-attenders at (i) a breast screening clinic, and (ii) a class teaching breast self-examination (BSE). The results show that attenders at one or other of the two services had much in common. However, attenders at the class appeared to be motivated by stronger feelings of vulnerability to breast cancer than attenders at breast screening. Also, differences in social class and educational background were found to be associated with attendance/non-attendance at the BSE class, but not associated with attendance at the breast screening clinic.

Aged↗
PubMedDate not supplied

Is breast self-examination predicted by knowledge, attitudes, beliefs, or sociodemographic characteristics?

The relationship of women's sociodemographic characteristics, knowledge, attitudes, and beliefs to breast self-examination (BSE) practice is not clear. We therefore studied these variables among older women at risk for developing breast cancer to determine which might be associated with the sensitivity, specificity, and frequency of BSE practice. We interviewed 300 women 40 to 68 years of age and measured BSE sensitivity and specificity using manufactured silicone breast models containing lumps. Of 54 variables and 10 scales examined univariately, six were associated with BSE sensitivity, one was negatively associated with specificity, and 10 were associated with frequency. No variable was associated with more than one component of BSE practice, and BSE frequency was not associated with BSE sensitivity or specificity. Using multivariate analysis, BSE sensitivity was best explained by type of employment, health interest, and perceived vulnerability to breast cancer, which accounted for approximately 16% of the variance. BSE frequency was best explained by intention to perform BSE, knowing how to perform BSE, using the correct method of BSE, self-confidence in the ability to perform BSE monthly, and self-confidence in the ability to find small lumps. These variables accounted for 27% of the variance. Sociodemographic characteristics, knowledge, attitudes, and beliefs poorly predicted how accurately women practiced BSE but somewhat better predicted how often women practiced BSE.

Adult↗
PubMed1985

Attributions, vulnerability, and psychological adjustment: the case of breast cancer.

This study examined the relationship between particular cognitions and psychological adjustment to breast cancer. It was hypothesized that adjustment would be positively associated with victims' perceptions of invulnerability to a recurrence of cancer and that victims' causal attributions for cancer would influence adjustment to the extent that the attributions contributed to or detracted from perceived invulnerability. A path model was developed based on the proposed association between invulnerability and adjustment, and attributions were tested for whether they directly or indirectly influenced adjustment. Responses from intensive interviews of 42 breast cancer victims were used to test the path model. Results strongly supported the hypothesized positive association between perceived invulnerability and adjustment and showed that the relationships between specific attributions and adjustment were mediated by vulnerability beliefs.

Adaptation, Psychological↗
PubMed2003

Are older cancer patients being referred to oncologists? A mail questionnaire of Ontario primary care practitioners to evaluate their referral patterns.

PURPOSE: Understanding why older patients are frequently underrepresented in cancer services use and clinical research may help to increase their participation in clinical trials and eventually result in better cancer care for this vulnerable population. METHODS: To identify potential barriers that may prevent older cancer patients from being referred from a primary care physician (PCP) to an oncology specialist, a self-administered questionnaire was mailed to 9,312 PCPs throughout Ontario. RESULTS: With a one-time mailing, 2,240 questionnaires were returned (response rate, 24%) of which 2,089 (93%) were assessable. Although 86% of respondents would refer most older patients with early-stage, potentially curable cancers to oncologists, only 65% would refer those with advanced-stage, potentially incurable cancers. The factors that most influence referral decisions of PCPs are patient's desire to be referred (69%), type (54%) and stage (49%) of cancer, and severity of cancer symptoms (49%). Other factors including age do not seem to influence the referral decision. Approximately 9% of respondents found it difficult to refer older cancer patients to oncology specialists, with the most commonly cited barriers being the length of waiting lists, mandatory tissue diagnosis before referral, and the belief that oncologists seldom relate to PCPs. CONCLUSION: Most PCPs stated that they would refer all elderly patients with cancer to oncologists and that referral decisions were based mainly on patients' wishes. Continued efforts are needed to overcome barriers in the referral process and to understand the perspectives of elderly patients to enhance their cancer care.

Aged↗
PubMed2005

Evaluation of LNA-modified DNAzymes targeting a single nucleotide polymorphism in the large subunit of RNA polymerase II.

Allele-specific inhibition (ASI) is a new strategy to treat cancer through a vulnerability created by the loss of large segments of chromosomal material by loss of heterozygosity (LOH). Using antisense approaches, it is possible to target single nucleotide polymorphisms (SNP) in the remaining allele of an essential gene in the tumor, thus killing the tumor while the heterozygous patient survives at the expense of the other nontargeted allele lost by the tumor. In this study, the feasibility of using locked nucleic acid (LNA)-modified DNAzymes (LNAzymes) of the 10-23 motif as allele-specific drugs was investigated. We demonstrate that incorporation of LNA into 10-23 motif DNAzymes increases their efficacy in mRNA degradation and that, in a cell-free system, the 10-23 motif LNAzyme can adequately discriminate and recognize an SNP in the large subunit of RNA polymerase II (POLR2A), an essential gene frequently involved in LOH in cancer cells. However, the LNAzymes, optimized under in vitro conditions, are not always efficient in cleaving their RNA target in cell culture, and the efficiency of RNA cleavage in cell culture is cell type dependent. The cleavage rate of the LNAzyme is also much slower than RNase H-recruiting DNA phosphorothioate antisense oligonucleotides. Moreover, compared with DNA phosphorothioates, the ability of the LNAzymes to differentially knock down two POLR2A alleles in cultured cancer cells is limited.

Base Sequence↗
PubMed1994

[Breast cancer screening: is family medicine intervention effective?].

A non-randomized controlled trial was conducted in two family medicine centers. The objectives were to evaluate whether or not a systematic prescription by family physicians of a screening mammography to women aged 50 to 69 belonging in majority to a disadvantaged socio-economic group, would permit to reach at least 60% of them and to explore which factors were associated with compliance to the prescription. The experimental intervention consisted in the prescription by the family physician of a mammogram to those patients found eligible for the screening procedure irrespective of the reason for encounter. A total of 468 of the 870 women who consulted a physician during the study period were eligible for a screening mammography. In the experimental group, the mammography prescription rate was 89% for eligible women. At the end of the study, 58.8% (95% Conf. Int.:51.9%-65.7%) of the women in the experimental group and 13.4% (95% Conf. Int.:9.4%-17.4%) of those in the control group had passed a mammography (p < 0.0001). The adjusted odds ratio for the family physician's intervention was 14.98 (95% Conf. Int.:7.86-28.58). Women over 60 years of age and those who perceived themself more vulnerable to breast cancer were more likely to respond positively to their physician's recommendation. This study confirms that family physicians can effectively reach, in the area of clinical prevention, individuals who might not be reached otherwise.

Aged↗
PubMed2025

Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions.

Understanding how genes influence drug responses is critical for advancing personalized cancer treatments. However, identifying these gene-drug interactions in a physiologically relevant human system remains a challenge, as it requires a model that reflects the complexity and heterogeneity among individuals. Here we show that large-scale CRISPR-based genetic screens, including knockout, interference (CRISPRi), activation (CRISPRa), and single-cell approaches, can be applied in primary human 3D gastric organoids to systematically identify genes that affect sensitivity to cisplatin. Our screens uncover genes that modulate cisplatin response. By combining CRISPR perturbations with single-cell transcriptomics, we resolve how genetic alterations interact with cisplatin at the level of individual cells and uncover an unexpected link between fucosylation and cisplatin sensitivity. We identify TAF6L as a regulator of cell recovery from cisplatin-induced cytotoxicity. These results highlight the utility of human organoid models for dissecting gene-drug interactions and offer insights into therapeutic vulnerabilities in gastric cancer.

Humans↗
PubMed1996

Vascular endothelial growth factor stimulates protein kinase C-dependent phospholipase D activity in endothelial cells.

Many tumors produce vascular endothelial growth factor (VEGF), a paracrine factor acting selectively on endothelial cells. VEGF has many effects on cultured endothelial cells and mediates angiogenesis and enhanced vascular permeability in vivo. The endothelial signal transduction pathways of VEGF represent novel targets for cancer therapy because they are readily accessible to systemically administered drugs. We have examined VEGF-stimulated signals generated in HUVEC to identify potential targets for therapeutic intervention. The transphosphatidylation reaction has been used to monitor phospholipase D (PLD) activity; total inositol phosphates have been measured after prelabeling of cells with [3H]myoinositol; and intracellular free calcium has been measured using Fura-2 fluorescence. After HUVEC-stimulation with VEGF, there is an early influx of calcium (maximal by 100 seconds) followed by activation of PLD (half maximal by 100 seconds, EC50 70 pm). The PLD activity was inhibited by reducing extracellular calcium (150 nM, 50% inhibition), exposure to 12-O-tetradecanoylphorbol 13 acetate (200 nM, 24 hours, 100% inhibition), Roche 31,8220 (10 microM, 15 minutes, 72% inhibition), or genestein (100 microM, 30 minutes, 56% inhibition), which suggests a dependence on both protein kinase C and tyrosine phosphorylation. Activation of phospholipase C-catalyzed hydrolysis of phosphatidylinositol-4,5-bisphosphate was inferred from the production of inositol phosphates, although this response was slower (half maximal by 3 minutes). The phospholipase C activity was also dependent on influx of calcium and was partially inhibited by low (150 nM) extracellular calcium. PLD may be involved in mediating a number of endothelial responses to tumor-secreted VEGF, notably cytoskeleton-dependent effects such as the cell migration involved in angiogenesis. This signal transduction pathway could represent an accessible and vulnerable target for cancer therapeutic intervention and has the novelty of being located within normal cells rather than tumor cells.

Calcium↗
PubMed2005

Hepatitis B and liver cancer beliefs among Korean immigrants in Western Washington.

Hepatocellular cancer occurs more frequently among Koreans, Vietnamese, and Chinese than other racial/ethnic groups in the U.S. This excess risk can be attributed to high rates of chronic hepatitis B viral (HBV) infection and low rates of HBV vaccination among Asian immigrants. However, there is little available information regarding the hepatitis B knowledge, beliefs, and practices among Koreans, the fifth-largest Asian population in the U.S. This brief report summarizes results from 30 qualitative interviews and two focus groups investigating hepatitis and liver cancer prevention, behavior, and beliefs among first-generation Korean immigrant adults ages 18-64 years residing in the Seattle-Tacoma metropolitan area of Washington State. The report concludes with suggestions for future investigations to address the high rates of chronic HBV infection and hepatocellular cancer in this vulnerable population.

Adult↗
PubMed1993

Targeting breast and cervical cancer screening to elderly poor black women: who will participate? The Harlem Study Team.

BACKGROUND: Factors associated with participation in breast and cervix cancer screening among elderly black women of low socioeconomic status were determined. METHODS: Data from a baseline cross-sectional random survey were used together with data on whether screening was subsequently completed or refused. The subjects were a random sample of women attending an urban public hospital primary care clinic for routine medical care with a birth year of 1924 or earlier. RESULTS: Among the 271 women in the study group, 70% completed screening. Stated intent was the strongest predictor of participation; women who intended to have both mammography and Pap testing were 2.7 times more likely to participate than those who intended to have neither test (95% confidence interval 1.4, 4.9; P < 0.01), controlling for age, insurance status, and level of chronic illness. Women who had more than three chronic illnesses were twice as likely to participate than those with three or fewer illnesses (95% confidence interval 1.1, 3.4 P < 0.02), controlling for the remaining variables. Other variables, including age, history of a recent screening examination, attitudes, or knowledge, were not related to participation. Stated intent was the only variable that predicted compliance with both mammography and Pap smear completion in separate regression models for the individual tests. CONCLUSION: A high proportion of elderly, socioeconomically disadvantaged black women will participate in cancer screening when it is offered in a primary care setting. Further research on behavioral intentions should be conducted to refine interventions designed to enhance the use of early cancer detection among vulnerable population groups.

Black or African American↗
PubMed2006

Postal workers' occupational and leisure-time sun safety behaviors (United States).

OBJECTIVES: United States Postal Service letter carriers are exposed to long bouts of UVR and thus are vulnerable to skin cancer. While previous studies have shown that occupational sun protection is often deficient, few studies have examined outdoor workers' behavior during leisure time. METHODS: Subjects (n = 2,660) self-reported widebrim hat and sunscreen use over the past five workdays and past two non-working days using Likert-type scales. Generalized linear mixed models and generalized estimating equations were used to compare hat and sunscreen rates and predictors during occupational and leisure time. RESULTS: On average, carriers spent 3.9 h outside during workdays and 3.3 h during non-working days. Sunscreen and widebrim hat use during the workday is low and rates of use are significantly lower during non-working days. CONCLUSIONS: Sun safety interventions for carriers should encourage sun protection at all times when outdoors.

Adult↗
PubMed1993

DMBA-induced mammary tumor growth in rats exhibiting increased or decreased ability to cope with stress due to early postnatal handling or antidepressant treatment.

Depression and an ability to cope with stress are suggested to play a role in the vulnerability to breast cancer. In rats, neonatal clomipramine administration induces subsequent behavioral abnormalities that closely resemble those seen in human endogenous depression. Early postnatal handling, on the other hand, improves subsequent ability to cope with stress in rodents. The present study examined whether early clomipramine treatment or handling influences the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats. Between postnatal days 5 and 20, rat pups were injected daily with 25 mg/kg clomipramine, handled either by holding them in a hand (H-handling) or by giving them a saline injection (I-handling), or left nonhandled. During these manipulations, but not later, body weight gain was lower in the I-handled and clomipramine-treated pups than in the H-handled rats. As adults, the time spent immobile in the swim test, a model of depressive behavior and an ability to cope with stress, was significantly lengthened in the clomipramine-treated female rats, and shortened in the handled females. Measurement of plasma 17-beta-estradiol (E2) did not reveal any significant differences between the groups. The percentage of animals developing mammary tumors was significantly higher, and the length of survival shorter among the clomipramine-treated rats than among the I-handled rats. However, both groups exhibited less tumors and longer survival than the nonhandled controls. There were no differences in mammary tumor incidence or survival between the nonhandled and H-handled rats.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Coping with additional stresses: comparative study of healthy and cancer patient new immigrants.

The adjustment and psychological distress of 166 cancer patients, who are new immigrants from the former Soviet Union, was assessed and compared to that of 288 healthy new immigrants from the the former Soviet Union. The healthy new immigrants had many adjustment problems and their psychological distress was fairly high. The cancer patients reported extremely severe psychological distress. In the healthy immigrants, age contributed to distress while family support had significant protective effects especially in the male immigrants. In the patients, these differences were even more extreme with family support being protective in the male group but not in the female group. Intrusiveness (IES) seems to be maladaptive adding to distress. The results clearly indicate that additional stresses, such as immigration, make cancer patients more vulnerable. The results also suggest possible interventions, especially those that will help to decrease intrusiveness.

Acculturation↗
PubMed1985

Explaining attendance at a breast-screening clinic.

This paper describes an analysis of the social, psychological and demographic factors associated with attendance/non-attendance at a clinic providing mammography and an examination carried out by medically-trained staff. Six hundred and fifty-four women aged 45-64 were interviewed approx. 1 month before they received an invitation to attend for breast screening. Seventy-two percent of these women subsequently attended the clinic. In all 30 different variables were measured. The attender could best be characterised as someone who previously used other types of preventive health service, felt vulnerable to breast cancer and saw breast screening as being beneficial. The implications of these and other findings are discussed.

Breast Neoplasms↗
PubMed2004

Autobiographical memories in patients treated for breast cancer.

OBJECTIVE: Previous research has shown that several clinical groups have difficulties with generating specific autobiographical memories. The aim of this study was to investigate autobiographical memory function in women who had been treated for breast cancer and to compare those patients who had undergone mastectomy only with those who had undergone breast reconstruction surgery after mastectomy. METHOD: A sample of 26 women treated for breast cancer were tested via telephone using the Autobiographical Memory Test (AMT). RESULTS: Breast cancer patients had difficulty retrieving specific autobiographical memories compared to a group of age-matched controls without any history of breast cancer. There were essentially no differences between the two patient groups. CONCLUSION: Since breast cancer patients are vulnerable to emotional distress, autobiographical memory deficits should be investigated further.

Adolescent↗