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PubMed1998

Polychlorinated biphenyls and human health.

Polychlorinated biphenyls (PCBs) were manufactured and used widely for many years. Because they are very persistent in both the environment and biological systems, there has been significant global contamination. This review presents a summary of known or suspected health effects of various PCB congeners, documented on the basis of both human and animal studies. As our knowledge increases several important points become apparent. PCBs interfere with many biological functions, including the immune system, the nervous system, and several endocrine system, and the fetus appears to be particularly vulnerable to these actions. PCBs cause certain cancers in animals. PCBs are mixtures of multiple congeners, differing on the basis of the numbers and positions of chlorines around the biphenyl ring, and it is becoming increasingly apparent that different congeners may have very different actions. These observations suggest that the potential human health hazards from PCB exposure have been underappreciated.

Animals↗
PubMed2001

The mysteries of the human genome uncovered--medicine is changed forever.

It is impossible to overemphasize the significance of the recent announcement that 85% of the DNA of the human genome has been decoded. Physicians can now begin teasing out the secrets of human health and disease. Within the next 10 years, it may be possible to determine who may be vulnerable to illnesses like Alzheimer's disease, cancer, and diabetes. The world of medicine will be utterly transformed in a few decades. Even before decoding of the human genome is completed, scientists have begun a new and more challenging research in explaining the molecular basis of life. "Proteonomics," the cataloging and analysis of every protein in the human body looms as the next major scientific medical effort. Proteins are more varied and complex than DNA. Fifty years from now, our understanding of the human organism and its various ills will be transformed beyond recognition through genomics and proteonomics. Stay tuned!

Disease Management↗
PubMed1979

Bracken carcinogenicity.

The study of bracken carcinogenicity affords an interesting example of the close alliance, with mutual benefit, between the work of veterinarians in the field and experimental research. On the one hand was the condition found in many parts of the world of bovine enzootic haematuria with uncertain aetiology and, on the other, the investigations conducted on the acute radiomimetic cattle bracken poisoning under laboratory conditions. The two have led to the recognition of the long term cancer dangers of bracken consumption and the vulnerability of a wide variety of species of animals. In these the types of tumour vary to include many organs other than the bladder, such as the gastrointestinal tract and blood forming tissues. Work on the search for the chemical compounds involved is described, together with the possible hazards, both mutagenic and carcinogenic, on an environmental basis.

Animals↗
PubMed1988

Detection and prevention of uterine cancer.

The two major uterine cancers, squamous carcinoma of the cervix and adenocarcinoma of the endometrium, are highly vulnerable to detection technology and, therefore, secondary prevention. High risk groups for each have been defined, cancer precursors described, i.e., dysplasia of the cervix and adenomatous hyperplasia of the endometrium, and efficient screening methods made available. For the cervical tumor cytologic testing is most appropriate, while histologic screening is more efficient for endometrial precursor lesions. The strategies of approach of these accessible tumors are models for detection and prevention methods elsewhere in the body and we should exploit them to virtual eradication of these uterine tumors.

Carcinoma↗
PubMed1996

DNA damage checkpoints: implications for cancer therapy.

DNA damage evokes a complex array of cellular responses, including cycle arrest in late G1 and/or G2 phases, and delayed progression through S phase. Arrest at these points in the cell cycle is governed, in large part, by a series of control systems, commonly termed "checkpoints". Activation of these checkpoints tends to protect cells from DNA damage by providing cells additional time to complete DNA repair. We discuss the impact of these DNA damage checkpoints on the chemosensitivity of human cancer cells. We focus on some of the complexities of the p53-dependent G1 checkpoint and review some recently discovered vulnerabilities in p53 disrupted cells that might be pharmacologically exploited for cancer treatment.

Animals↗
PubMed2003

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers.

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.

Alcohol Dehydrogenase↗
PubMed2004

Correlates of cervical cancer screening among underserved Hispanic and African-American women.

BACKGROUND: Substantial subgroups of American women, specifically those of ethnic minorities, have not been screened for cervical cancer or are not screened at regular intervals. The rates for receipt of female-related cancer screening tests remain far below the goals set forth in Healthy People 2010. OBJECTIVE: This study applied a well-known, recently revised theoretical model of health care access and utilization, the Behavioral Model for Vulnerable Populations, to examine the correlates of the adherence to cervical cancer screening guidelines among publicly housed Hispanic and African-American women, two of the most vulnerable segments of our population. METHODS: This study conducted a cross-sectional survey of a community-based random sample of 230 African-American and Latino female heads of household, from a geographically defined area, the three urban public housing communities in Los Angeles County, CA. RESULTS: Only 62% of our sample had received a screening for cervical cancer within the past year. Yet, 29% of the sample claimed that no health care provider had ever told them that they needed a screening test for cervical cancer. Hispanic and older women are by far less likely to adhere to screening guidelines; in this study, 51% of Hispanics and 22% of African-Americans reported no screening within the last year. Multivariate analysis shows that affordability, continuity of care, and receiving advice from health care providers regarding a Papanicolaou (Pap) smear were significant predictors of up-to-date to cervical cancer screening. CONCLUSION: This study documents a significant disparity in screening for cervical cancer among underserved minorities, particularly Hispanic, uninsured, and older women. The continuity of obtaining medical services and receiving recommendations from physicians remain the core factors that are significantly associated with obtaining cervical cancer screening. These results underscore the need for continued efforts to ensure that medically underserved minority women have access to cancer screening services.

Adult↗
PubMed1994

Culturally sensitive breast cancer screening programs for older black women.

Breast cancer is the leading cause of cancer mortality among black women. Elderly black women are particularly vulnerable and suffer the "double jeopardy" effect of older age and minority status. Older black women are not benefiting from the early detection provided through breast cancer screening. Factors that prevent this population from using breast cancer screening include cost, accessibility, availability, lack of knowledge, health care provider variables, and lack of community involvement. Breast cancer screening programs are needed that address cultural diversity to screen women who presently are not seen according to established guidelines. This article focuses on the need for primary care providers to offer culturally sensitive breast cancer screening programs designed for the older black woman. A model is presented based on Leininger's Culture Care Theory and the Health Belief Model. Specific strategies to increase the older black woman's participation in breast cancer screening practices are described.

Black or African American↗
PubMed1997

Impact of parental anxiety on child emotional adjustment when a parent has cancer.

PURPOSE/OBJECTIVES: To describe the relationships among parent anxiety, child anxiety, and emotional adjustment in children who have a parent with cancer. DESIGN: Correlational. SETTING: A large cancer center in the southeastern United States. SAMPLE: Thirty-three child/parent with cancer dyads. METHODS: Research packets were mailed to child/parent dyads who agreed to participate in the study. Parents completed a demographic questionnaire, a Spielberger State-Trait Anxiety Scale, and a Personality Inventory for Children (PIC). Children completed the child version of the Spielberger State-Trait Anxiety Scale. MAIN RESEARCH VARIABLES: Parent anxiety, child anxiety, and child adjustment. FINDINGS: Children who have a parent with cancer and parents who have experienced cancer report significantly higher state and trait anxiety compared to a normed population sample. Parental reports on the PIC indicated that latency-aged children (i.e., 6-12 years) showed significantly greater internalization and somatic symptoms compared to the sample norm. Parent state anxiety was negatively correlated with children's internalization and somatic symptoms. Parental anxiety accounted for the greatest variance in child adjustment. IMPLICATIONS FOR NURSING PRACTICE: These study findings may provide nurses with a better understanding of the vulnerability of children who have a parent with cancer and can build a foundation for the development of supportive interventions for these children.

Adaptation, Psychological↗
PubMed2004

Hsp90: the vulnerable chaperone.

The molecular chaperone Hsp90 has emerged as an important target in cancer treatment because of its roles in maintaining transformation and regulating the function of proteins involved in apoptotic, survival and growth pathways. Many Hsp90 inhibitors function by binding to the N-terminal ATP pocket, but the chaperone has many other vulnerable points. Agents that interact with its C-terminus or modify its post-translational status represent additional ways of interfering with chaperone activity. This review will discuss several emerging classes of Hsp90 inhibitors and their modes of action.

Animals↗
PubMed2025

Intermediately Methylated Regions in Normal Cells Are Epimutation Hotspots in Cancer.

DNA methylation is altered in all cancers, but the mechanisms responsible for these changes are not well understood. Using data from 100 primary samples, we show that regions with intermediate methylation in normal hematopoietic cells are hotspots for stable, clonal epimutations in acute myeloid leukemia. Analysis of hematopoietic stem cell clones demonstrated that intermediate methylation at epimutation hotspots reflects random allele-specific methylation and expression at the single cell level, representing a previously unrecognized form of somatically acquired imprinting. We identified somatically imprinted regions in other tissues and show they are epimutation hotspots in other cancer types. This demonstrates that random allele-specific methylation is both a general property of normal cells, and a vulnerability that renders them susceptible to cooperating events and clonal selection during cancer.

Journal Article↗
PubMed1991

Life events prior to manifestation of breast cancer: a limited prospective study covering eight years before diagnosis.

The role of life events in breast cancer was conceptualized within two models differing by vulnerability factors, 'social support' and 'early loss of mother'. The eight years prior to manifestation of the lump were covered by semi-structured interviews. Event ratings were performed according to Brown and Harris' Life Events and Difficulties Scale, an interviewer-based rating method. Data were collected within a so-called limited prospective design. This setting was subject to critical evaluation to control possible artifacts. Interviews were tape-recorded and rated before learning the final diagnosis. In the tumor groups, 97 women with a suspicious breast lump were interviewed immediately after hospital admission. In 33 cases, the diagnosis turned out to be malign, 59 had a benign result. Data analysis revealed that life events in the severest categories were reported most often in the cancer group. Path analyses showed that effects do not disappear when control variables are taken into account.

Adaptation, Psychological↗
PubMedDate not supplied

Testicular versus breast and colorectal cancer screening: early detection practices of primary care physicians.

Testicular cancer is the most common solid tumor among men 20 to 34 years old, and it accounts for one of every seven deaths in late adolescent and young adult men. However, studies during the past 20 years continue to show that a majority of men in the most vulnerable ages are unaware of their risk for testicular cancer, deny having had testicular examinations as a part of their routine physical assessments, and lack knowledge of testicular self-examination techniques. This descriptive study used a mailed questionnaire and evaluated self-reported testicular cancer detection behaviors among primary care physicians (N = 116). Breast exams and colorectal screening were included for masking and comparative purposes. Forty-nine percent of the physicians reported routinely performing age-appropriate testicular exams on patients, in contrast to performing breast (83%) and colorectal exams (68%). Instructing male patients to perform testicular self-examination was reported as a routine procedure by 29%, and breast exams were taught routinely by 86% of the physicians. Providing an opportunity for patients to give a return demonstration of the technique was reported 16% of the time for breast self-examination and 4% of the time for testicular self-examination. Teaching patients to do appropriate self-examinations can enhance the provider-client partnership in the provision of healthcare. When providers do not teach the patient to perform self-examinations, a valuable opportunity is missed.

Adolescent↗
PubMed2026

EZH1/2 inhibition selectively targets SMARCA4/2 co-deficient lung cancer cells by suppressing stemness and proliferation.

SMARCA4-deficient thoracic malignancies comprise biologically heterogeneous tumors, ranging from conventional non-small cell lung cancer with SMARCA4 alterations to thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT), an aggressive entity frequently associated with concomitant SMARCA2 loss. However, the extent to which SMARCA4-deficient lung cancer cell lines recapitulate SMARCA4-UT-like biology remains incompletely defined. Here, we characterized lung cancer cell lines across distinct SMARCA4 and SMARCA2 states and identified a subgroup with SMARCA4/2 co-deficiency that exhibited reduced expression of epithelial lineage markers and transcriptional similarity to SMARCA4-UT and other SWI/SNF-deficient malignancies. The EZH1/2 inhibitor HM97662 selectively suppressed growth in SMARCA4/2-deficient cells, with limited effects in SMARCA2-proficient cells. EZH1/2 inhibition broadly reduced H3K27me3 and induced derepression of PRC2 targets regardless of drug sensitivity. However, its biological effects were most pronounced in SMARCA4/2-deficient cells, where it promoted apoptosis, reduced stemness marker expression, attenuated the SMARCA4-UT-associated transcriptional signature, and suppressed proliferative and mTORC1-related programs. Chromatin accessibility analysis further revealed cell-line-specific patterns of accessibility loss, with reduced accessibility at stemness-associated transcription factor motif-enriched regions coupled with transcriptional repression of nearby genes in SMARCA4/2-deficient cells. These findings support dual EZH1/2 inhibition as a potential therapeutic vulnerability in SMARCA4/2-deficient, SMARCA4-UT-like lung cancer cells.

Humans↗
PubMed1991

What healthy women think, feel and do about cancer, prevention and breast cancer screening in Italy.

In preparation for a major campaign to encourage participation in a breast screening programme for all women between 50-70 years old in Florence, Italy, an in-depth study of 200 women's attitudes and practices regarding cancer and its prevention was undertaken. 72% participated in semistructured interviews, and inclination to participate was analysed in terms of Yes (39%), Uncertain (36%), and No (20%) (5% were unspecified). Age (P = 0.03), area of birth (P = 0.01), education level of husband (P = 0.04) and prior Pap smear (P = 0.00) or mammography (P = 0.00) were among the variables statistically associated with inclination to participate. While the women shared more or less common images of cancer, concern for health, and belief in the importance of God and destiny, those less inclined to participate felt less personally vulnerable, had less faith in medicine's ability to cure or prevent cancer, were more distant from the medical system and culture in general and regarded information about health or illness more as unnecessary or dangerous than beneficial. Understanding and consideration of both "popular" and "medical" cultures need to be encouraged.

Aged↗
PubMed1990

[Hereditary site-specific colon cancer--report of two families].

Five cases of hereditary site-specific colon cancer (HSSCC or Lynch syndrome I) from two families are reported. The main features of HSSCC are: an autosomal dominant model of heredity, the absence of associated polyposis, the average age being younger, vulnerable site being the right colon (4/5 cases), multiple colon cancers (3/5 cases) and long survival. These 5 cases possessed the above mentioned features. Having no special detection method, the authors suggest that the members of these families be registered and the high risk members regularly checked.

Adenocarcinoma↗
PubMed2026

Unraveling lung cancer complexity: Spatial omics in tumor microenvironment characterization and precision medicine.

Heterogeneous tumor microenvironment (TME) in lung cancer plays a crucial role in disease progression and resistance to therapy. Despite advances in single-cell and bulk omics profiling, these methods often overlook spatial context, which is vital for understanding cell-cell interactions and regional heterogeneity. In recent years, spatial omics technologies-including spatial genomics, transcriptomics, proteomics, and metabolomics-have revolutionized the ability to map molecular landscapes while maintaining tissue architecture. These advancements have become essential components of next-generation lung cancer management. By providing unprecedented resolution in characterizing the lung cancer TME, spatial omics could reveal prognostic and predictive biomarkers and identify new therapeutic vulnerabilities. This review will provide the first critical evaluation of spatial multi-omics approaches for lung cancer prognosis. It will also assess various integration strategies for multi-omics data to explore the clinical translational potential of these tools for therapy selection and patient stratification. Therefore, a deeper understanding of spatial omics technologies and their application in lung cancer can significantly improve precision diagnostics and therapeutic decision-making.

Lung cancer↗
PubMed2005

Present and future options for the preservation of fertility in female adolescents with cancer.

Fertility and sexuality are important aspects in the quality of life of long-term survivors of cancer. Adolescents in particular are in a very vulnerable period of their lives with respect to future fertility and sexuality. Special attention should be paid to preserve their fertility whenever possible. The gonadotoxic effect of chemotherapy is largely drug- and dosedependent and is related to age. The effect of radiotherapy is also dependent on dose and age and on the radiation therapy field. The prepubertal ovary is the least susceptible to gonadotoxicity. Ablative regimens for stem cell transplantation have an extremely high risk of ovarian failure. Alternative chemotherapy protocols can reduce long-term gonadotoxicity. Alkylating agents impose the highest risk in causing ovarian failure and should be avoided whenever possible. Up to now, the results of gonadoprotective hormonal therapy have been disappointing and contradictory. Transposition of the ovaries should be considered in each case of planned pelvic or whole body irradiation, where ovarian involvement is unlikely and chemotherapy not necessary. Cryopreservation of preimplantation embryos will seldom be possible in female adolescents due to the lack of a stable relationship with a male partner. Cryopreservation of mature and immature oocytes (necessitating in vitro maturation) is still assumed not to be safe for the offspring. Cryopreservation and transplantation of ovarian tissue seems to be the most promising way of future fertility preservation in female adolescents. At present, it is in its early experimental stage. Its safety and possibilities for fertility preservation in humans are not proven as yet. Additionally, technical and ethical issues need to be addressed. The counseling of female adolescents who are facing the threat of cancer needs careful consideration with regards to the psychosocial impact of the treatment and its consequences. Special attention should be paid to aspects of future quality of life, in particular: fertility and sexuality.

Adolescent↗