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PubMed2005

Breast cancer recurrence dynamics following adjuvant CMF is consistent with tumor dormancy and mastectomy-driven acceleration of the metastatic process.

PURPOSE: The aim of this study was to better understand human breast cancer biology by studying how the timing of metastasis following primary resection is affected by adjuvant CMF (cyclophoshamide, methotrexate, 5-fluorouracil) chemotherapy. PATIENTS AND METHODS: Discrete hazards of recurrence and recurrence risk reductions for treated patients relative to controls were analyzed for all patients enrolled in two separate randomized clinical trials [study 1 (386 women): no further treatment versus 12 cycles of CMF; study 2 (459 women): six versus 12 cycles of CMF] and a historical group (396 women: surgery alone) of axillary node-positive patients undergoing mastectomy. RESULTS: (i) Nearly all CMF benefit occurs during the first 4 years following resection/chemotherapy. (ii) The CMF recurrence rate reduction is largely restricted to two specific spans. These temporally separate recurrence clusters occur during the first and third year of follow-up, while the second-year recurrences are weakly affected. (iii) Prolonging adjuvant treatment from 6 to 12 months partially alters this recurrence timing, without appreciably affecting the overall recurrence rate. (iv) These effects upon the dynamics of post-resection occurrence are menopausal status-independent. CONCLUSIONS: At least two different therapeutically vulnerable proliferative events, resulting in clinical appearance of two metastasis temporally distinct clusters of post-resection cancer recurrence, apparently occur during the administration of adjuvant chemotherapy. Metastases that transpire outside of these temporal windows are refractory to adjuvant therapy. The dynamics of both post-treatment recurrence risk and CMF effectiveness are similar for both pre- and postmenopausal women, suggesting that post-resection mechanisms by which chemotherapy prevents metastases are similar, but of different magnitude in pre- and postmenopausal women. These findings are consistent with a metastasis model that includes tumor dormancy in specific micrometastatic phases (single cells and avascular foci) and with the acceleration of the metastatic process by the surgical resection of the primary breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

[Experiencing the disease of breast cancer and getting life under control again].

Women experiencing breast cancer are confronted with a live threatening disease and find themselves in a situation that changes and restricts their life psychologically, physically and socially. This qualitative investigation examined the experience of living with breast cancer from the perspective of newly diagnosed women. Ten women were interviewed at the end of their radiotherapy. The interviews are analysed with the method of content analysis. The findings show three domains. First domain: From living in fear of having breast cancer to the confirmation of its diagnosis. These women perceive the confirmation of the diagnosis as a shock and initially plunge into an existential crisis. The life threatening disease with an unpredictable future, feelings of vulnerability, uncertainty, hopelessness and anxiety often make them depressed. They need all their energy to maintain control over their life, by suppressing emotions to protect themselves from overwhelming feelings and suffering. Second domain: Experiencing the therapy. The women undergo weakening aggressive and invasive treatment regimes, leaving them in a condition worse than before. Physically exhausted, they sometimes don't know how to go through and overcome this time. Lack of energy, tiredness and fatigue are ongoing problems. Being diagnosed with breast cancer, the suddenly become patients, having to cope with a complex healthcare system. From doctors and nurses they expect empathy, caring and expertise. When in contact with health care, they often hide their suffering, while in fact, they are extremely vulnerable and in deep despair. Third domain: Hold out and live. Women living with breast cancer have no choice but to go through this situation. By motivating their self they regain and mobilise their vital energy. They try to suppress their suffering and dark, intrusive memories. Support from relatives is very important, however, such women tend to protect them from their suffering. The definition of the role of these relatives and their suffering remain unclear. In a future study, research is needed to determine precisely which psychosocial variables are effective in promoting greater health for women with breast cancer and their families, taking into consideration the dynamic of the relationship between women with breast cancer and their relatives as well as the influence of their mutual support.

Adaptation, Psychological↗

PubMed2025

Ferroptosis in Oral Cancer: Mechanistic Insights and Clinical Prospects.

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a pivotal vulnerability in oral squamous cell carcinoma (OSCC). This review provides an overview of ferroptosis mechanisms and their implications for OSCC pathobiology and therapy. OSCC cells exhibit heightened reliance on anti-ferroptotic defenses such as GPX4, SLC7A11, FSP1, and Nrf2, and disrupting these pathways suppresses tumor growth and restores sensitivity to chemotherapy, radiotherapy, and immunotherapy. Genetic and epigenetic regulators, including p53, PER1, circ_0000140, and STARD4-AS1, critically modulate ferroptotic sensitivity, while metabolic enzymes such as ACSL4, LPCAT3, and TPI1 link ferroptosis to cellular plasticity and resistance. Preclinical studies highlight the promise of small-molecule inhibitors, repurposed agents (e.g., sorafenib, artesunate, trifluoperazine), natural compounds (e.g., piperlongumine, Evodia lepta, quercetin), and nanomedicine platforms for targeted ferroptosis induction. We further address ferroptosis within the tumor microenvironment, highlighting its immunogenic and context-dependent dual roles, and summarize genomic and transcriptomic evidence linking ferroptosis-related genes to patient prognosis. Beyond cancer, ferroptosis also contributes to non-malignant oral diseases, including pulpitis, periodontitis, and infection-associated inflammation, where inhibitors may protect tissues. Despite these advances, clinical translation is constrained by the lack of safe ferroptosis inducers and validated biomarkers. Future research should focus on developing pharmacologically viable GPX4 inhibitors, refining biomarker-driven patient stratification, and designing multimodal regimens that combine ferroptosis induction with standard therapies while preserving immune and tissue integrity. Ferroptosis therefore represents both a mechanistic framework and a translational opportunity to reshape oral oncology and broader oral disease management.

Humans↗

PubMed1985

Vulnerability to stress among women with in utero diethylstilbestrol (DES) exposed daughters.

In utero exposure to diethylstilbestrol (DES) was initially linked to vaginal-cervical cancer and subsequently to reproductive difficulties. These unanticipated and ongoing health risks to female offspring may constitute a chronic source of stress for DES mothers. We interviewed 60 mothers of exposed daughters and 30 acquaintance controls. Two hypotheses were tested in regard to DES mothers: DES discovery and its aftermath have a direct, long-term, negative effect on psychological health and the DES experience intensifies the negative psychological effects of other adverse life circumstances. To operationalize psychological health, we measured symptoms of "demoralization" and positive health practices--the latter as a behavioral indicator of mastery and personal control. We also measured adversities that may mediate the threat posed by DES, including stressful events, medical problems, and chronic burdens. We found DES history to be associated with poorer psychological health only when mothers encountered other losses and threats to themselves and their families. We concluded that DES mothers may manifest increased vulnerability to subsequent stresses in their lives.

Adaptation, Psychological↗

PubMed1987

Unresolved grief in persons with cancer referred for psychotherapy.

Of 135 persons with cancer referred for psychotherapy, 76 per cent were found to have had a previous grief experience, and 60 per cent were suffering from unresolved grief for previous losses. This article discusses the identification of those most vulnerable to unresolved grief in later life and discusses the problems previous losses have on one's ability to deal with the current crisis of a diagnosis of cancer. The impact of early childhood loss, identification with the deceased, chronic grief, delayed grief, exaggerated or masked grief, and the death of a dream are discussed, and clinical examples are used to illustrate concepts of intervention.

Adolescent↗

PubMed2001

Sexual functioning after treatment for testicular cancer--review and meta-analysis of 36 empirical studies between 1975-2000.

Literature concerning sexual functioning after treatment for testicular cancer from 1975-2000 is reviewed. After a literature search in Medline and Psylit was conducted, as well as a search for cross-references made, a meta-analysis was performed. To describe sexual functioning, several aspects of the sexual response cycle were used: sexual desire, sexual arousal, erection, and orgasm; ejaculatory function, sexual activity, and sexual satisfaction were used as well. The number of patients included in the studies as well as treatment modalities were taken into account. A total of 36 relevant studies was screened (28 retrospective and 7 prospective studies), concerning 2,786 cases of testicular cancer. Meta-analysis revealed that ejaculatory dysfunction was reported most frequently and was related to surgery in the retroperitoneal area. Erectile dysfunction was related to irradiation, but was reported least frequently. Other sexual functions were not related to treatment modality. Meta-analysis revealed no deterioration of sexual functioning in the course of time, except a decrease in sexual desire and an increase in sexual satisfaction. Retrospective studies reported more sexual dysfunction than did prospective studies. Detailed analysis of separate studies, however, revealed a wide variation in reported sexual morbidity, as well as in assessment methods. Somatic consequences of disease and treatment may reduce ejaculation; however, other aspects of sexual functioning are not clearly related to disease- or treatment-related factors and may instead refer to a psychological vulnerability caused by one's confrontation with a life-threatening, genito-urinary disease, such as testicular cancer.

Erectile Dysfunction↗

PubMed2003

Effect of H(2)O(2) on cell cycle and survival in DNA mismatch repair-deficient and -proficient cell lines.

Patients who develop tumors with Lynch syndrome, which is caused by mutational inactivation of the DNA mismatch repair (MMR) system, have a relatively favorable prognosis compared to patients who develop sporadic tumors. Paradoxically, DNA MMR-deficient cells are resistant to many chemotherapeutic agents, and are capable of bypassing the G2/M checkpoint in vitro. Colon cancers that develop in the setting of Lynch syndrome show an abundant recruitment of immune cells into tumor tissues, which might be expected to increase oxyradical formation, and make the tumor cells more vulnerable to cell death. We examined the chemosensitivity and cell cycle response to oxidative stress in several MMR-deficient (HCT116, SW48, and DLD1) and -proficient (CaCo2, SW480, and HT29) colorectal cancer cell lines. H(2)O(2) induced a G2/M cell cycle arrest in both MMR deficient and proficient cell lines, however MMR-deficient cell lines were more sensitive to H(2)O(2) toxicity, and the response was more prolonged in MMR-deficient cells. Interestingly, human MutL-homologue (hMLH1-)defective HCT116 and hMLH1-restored HCT116+ch3 cell lines responded to H(2)O(2) with the same degree of G2/M arrest. The survival response of HCT116+ch3 was nearly identical to that of hMLH1-defective HCT116+ch2, although better than the response observed in HCT116 cells. In conclusion, greater cellular sensitivity and G2/M arrest in response to oxidative stress in MMR-deficient colorectal cancer cells could be one of the reasons for the more favorable prognosis seen in patients with Lynch syndrome. However, this sensitivity appears not to be a direct result of a deficient MMR function, but is more likely attributable to spectrum of target gene mutations that occurs in MMR-deficient tumors.

Adaptor Proteins, Signal Transducing↗

PubMed1994

Attitudes about genetic testing for breast-ovarian cancer susceptibility.

PURPOSE: In anticipation of the availability of genetic testing for a breast-ovarian cancer susceptibility gene (BRCA1), this study examined interest in and expectations about the impact of a potential genetic test. PATIENTS AND METHODS: The subjects were 121 first-degree relatives (FDRs) of ovarian cancer patients. The design was cross-sectional. Subjects completed a structured telephone interview of attitudes about cancer and genetic testing, and self-report psychologic questionnaires to assess coping style and mood disturbance. RESULTS: Overall, 75% of FDRs said that they would definitely want to be tested for BRCA1 and 20% said they probably would. In bivariate analyses, interest was associated positively with education, perceived likelihood of being a gene carrier, perceived risk of ovarian cancer, ovarian cancer worries, and mood disturbance. In logistic regression analysis, perceived likelihood of being a gene carrier was associated strongly with interest (odds ratio, 3.7; P = .006). Results of stepwise linear regression modeling indicated that an anticipated negative impact of genetic testing was associated with being younger (beta = -.66, P = .009), having more mood disturbance (beta = .015, P = .01), and having an information-seeking coping style (beta = .19, P = .002). CONCLUSION: These results suggest that the demand for genetic testing for BRCA1 among FDRs of cancer patients may be great. Moreover, those who elect to participate may represent a more psychologically vulnerable subgroup of high-risk women.

Adolescent↗

PubMed2005

Implications of statin adverse effects in the elderly.

The elderly differ from younger people in the relation of cholesterol to heart disease and mortality. Clinical trial evidence supports epidemiological findings in showing that high cholesterol weakens in its relationship to heart disease with age and loses (and in older age reverses) its relation to mortality. Randomised trial data confirm that lowering cholesterol no longer extends life in the elderly, even those at high risk of heart disease, and no evidence supports the presumption that the impact on all-cause morbidity is any more favourable. These findings increase the importance of statin adverse effects (AEs) in this group. Furthermore, the elderly may be more vulnerable to known AEs, and evidence provides cause for concern that new risks may supervene, including cancer, neurodegenerative disease and heart failure. Physiological evidence regarding the impact of statins on mitochondrial function, and mitochondrial function on ageing, support these concerns. Additionally, the impact of statin AEs (e.g., muscle and cognitive problems) may be amplified in this group. Effects may be misattributed to ageing. Even modestly lower cognitive and physical function in older elderly prognosticates increased disability, hospitalisation, institutionalisation, and mortality. Disability, once present, is less likely to recover. Because the risk for AEs is unattended by evidence of net benefit to the person, the use of statins in the elderly should be undertaken, if at all, with circumspection and close scrutiny for adverse effects.

Age Factors↗

PubMed1991

Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts.

The incidence of breast cancer was determined in 4940 women treated for tuberculosis between 1925 and 1954 in Massachusetts. Among 2573 women examined by X-ray fluoroscopy an average of 88 times during lung collapse therapy and followed for an average of 30 years, 147 breast cancers occurred in contrast to 113.6 expected [observed/expected (O/E) = 1.29; 95% confidence interval (CI) = 1.1-1.5]. No excess of breast cancer was seen among 2367 women treated by other means: 87 observed versus 100.9 expected. Increased rates for breast cancer were not apparent until about 10 to 15 years after the initial fluoroscopy examination. Excess risk then remained high throughout all intervals of follow-up, up to 50 years after first exposure. Age at exposure strongly influenced the risk of radiation-induced breast cancer with young women being at highest risk and those over age 40 being at lowest risk [relative risk (RR) = 1.06]. Mean radiation dose to the breast was estimated to be 79 cGy, and there was strong evidence for a linear relationship between dose and breast cancer risk. Allowing for a 10-year minimum latent period, the relative risk at 1 Gy was estimated as 1.61 and the absolute excess as 10.7 per 10(4) woman-years per gray. When compared to other studies, our data suggest that the breast is one of the most sensitive tissues to the carcinogenic force of radiation, that fractionated exposures are similar to single exposures of the same total dose in their ability to induce breast cancer, that risk remains high for many years after exposure, and that young women are especially vulnerable to radiation injury.

Breast Neoplasms↗

PubMed2026

Lymphangiogenesis-related gene signature-based risk model for prognostic assessment of cervical cancer: immune-metabolic characterization and molecular subtype analysis.

BACKGROUND: Lymphangiogenesis promotes tumor dissemination and may shape the immune contexture of cervical cancer, yet lymphangiogenesis-related prognostic stratification and its immunometabolic implications remain insufficiently defined in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). METHODS: TCGA-CESC transcriptomes and clinical data were obtained from UCSC Xena and integrated with normal cervix tissues from the Genotype-Tissue Expression Project after batch correction. Prognostic LYMRGs were first identified from the differentially expressed set using univariable Cox proportional hazards analysis. Candidate genes were then reduced using an L1-regularized Cox model (Least Absolute Shrinkage and Selection Operator), and the remaining markers were entered into a multivariable Cox regression to obtain the final coefficients and compute an individualized risk score. The model's prognostic value was further assessed in an independent Gene Expression Omnibus dataset. In addition, expression patterns of the signature genes were leveraged for molecular subtyping of TCGA samples via non-negative matrix factorization (NMF). Immune infiltration and immunotherapy-associated characteristics were interrogated through a multi-algorithm strategy (single-sample gene set enrichment analysis, CIBERSORT, ESTIMATE, Tumor Immune Dysfunction and Exclusion (TIDE), and Immunophenoscore . Additional analyses included pathway enrichment (GSEA/GO/KEGG), drug sensitivity prediction (pRRophetic/CellMiner), and ceRNA network analysis. RESULTS: A six-gene LYMRG signature robustly stratified survival. High-risk patients had significantly worse overall survival in The Cancer Genome Atlas with AUCs of 0.819/0.801/0.801 at 1/3/5 years, and in GSE52903 (P = 0.001) with AUCs of 0.733/0.719/0.725. NMF identified two subtypes with distinct prognosis (P = 0.01) and divergent immune landscapes. Risk groups and subtypes exhibited consistent differences in immune infiltration, checkpoint expression, TIDE/IPS patterns, and pathway enrichment. Predicted chemosensitivity differed by risk group, and the ceRNA network suggested candidate upstream lncRNA regulators of the signature. CONCLUSION: A lymphangiogenesis-related six-gene model enables clinically meaningful prognostic stratification of CESC and links lymphangiogenesis programs to distinct tumor immune phenotypes and therapeutic vulnerabilities.

cancer↗

PubMed2004

How can experiences of patients and carers influence the clinical care of large bowel cancer?

A qualitative project was designed to investigate the care of large bowel cancer from patients' and carers' perspectives using semi-structured interviews; tape-recorded, transcribed and analysed; to identify recurrent themes. Forty-nine patients treated surgically for bowel cancer from three hospital trusts in West Surrey were visited at home, and eight of their carers attended a focus group from a choice of three geographical locations. Five main themes identified: experience of symptoms; general practitioner (GP) management; impact of diagnosis; perceptions of clinical care and treatment; information needs. Results showed that patients and carers were ignorant of the symptoms and signs of large bowel cancer and wanted more information. They were satisfied when the GP took symptoms seriously and referred promptly. Three groups of patients were particularly vulnerable: those requiring stomas (25), those diagnosed with polyps initially (11) and patients admitted as an emergency (7). Specialist nurses were seen as the main source of written information and support, which was most needed at the time of diagnosis and discharge. The public needs more accessible information about the symptoms and signs of bowel cancer. Referral to multiprofessional bowel cancer teams is essential to provide appropriate support and clear information from the time of diagnosis throughout the care pathway. Recommended strategies for improving clinical care are outlined.

Adult↗

PubMed1999

A case-control study of malignant melanoma in Israeli kibbutzim.

BACKGROUND: Incidence rates for malignant melanoma in Israel are rising steadily, and the kibbutz population is at increased risk for this malignancy. OBJECTIVES: To assess the risk factors for malignant melanoma among kibbutz members compared to matched healthy controls. METHODS: We conducted a case-control study of 168 malignant melanoma patients and 325 healthy controls, matched by age and gender. Data were collected on three categories of risk: demographic, personal (e.g., skin, eye and hair color), and environmental/behavioral (e.g., sun exposure, use of sunscreens). RESULTS: There were no differences between the groups regarding sociodemographic data. Significantly more patients than controls had fair, vulnerable skin (P < 0.001), light eyes (P < 0.05), and fair hair (P < 0.001). There was no difference in family history of malignant melanoma or other cancers. Patients with malignant melanoma had significantly more additional skin lesions (e.g., keratoses) (P < 0.001). More patients than controls recalled having been exposed to the sun for long periods when they were 6-13 years of age. A conditional logistic regression analysis showed that fair hair, fair vulnerable skin, and additional skin lesions were independently associated with malignant melanoma (P < 0.01). CONCLUSIONS: The main target population for interventions to reduce the incidence of malignant melanoma among kibbutz members should be individuals with these risk factors. A history of increased exposure to the sun from age 6 to 13 should also be taken into account as an independent risk factor.

Adult↗

PubMed2005

Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials.

PURPOSE: Older patients are significantly underrepresented in cancer clinical trials. A literature review was undertaken to identify the barriers that impede the accrual of this vulnerable population onto clinical trials and to determine what specific strategies are needed to improve the representation of older patients in research studies. METHODS: A systematic literature search was undertaken using several different strategies to identify relevant articles. RESULTS: Nine of 31 relevant papers from 159 citations were included. Age is a significant barrier to recruitment; only a quarter to one third of potentially eligible older patients are enrolled onto trials. Physicians' perceptions, protocol eligibility criteria with restrictions on comorbid conditions, and functional status to optimize treatment tolerability are the most important reasons resulting in the exclusion of older patients. Other barriers include the lack of social support and the need for extra time and resources to enroll these patients. Conversely, older patients do not view their age as an important reason for refusing trials. CONCLUSION: Specific clinical trials confined to older patients should be conducted to evaluate tumor biology, treatment tolerability, and the effect of comorbid conditions. Protocol designs need to stratify for age and be less restrictive with respect to exclusions on functional status, comorbidity, and previous cancers, such that results are generalizable to older patients. Physician education to dispel unfounded perceptions, improved access to available clinical trials, and provision of personnel and resources to accommodate the unique requirements of an older population are possible solutions to remove the barriers of ageism.

Age Factors↗

PubMed2005

Primary prevention of human papillomavirus-dependent neoplasia: no condom, no sex.

Cervix cancer is one of several neoplastic disorders that arise following transfer of human papillomavirus (HPV) during unprotected sexual intercourse, and like most other sexually transmitted diseases (STDs), is largely preventable by consistent condom use. This primary prevention strategy has received little support, however, when compared with massive secondary prevention initiatives involving cervical screening. The reasons for this anomalous situation are complex, and include: (i) the asymptomatic nature of most primary HPV infections; (ii) widespread ignorance concerning the venereal aetiology of HPV-related cancers; (iii) the common but incorrect belief that condom use does not reduce HPV transmission; (iv) the perceived irrelevance of safe sex campaigns based on reducing transmission of human immunodeficiency virus (HIV) in high-HPV but low-HIV countries such as the Philippines; (v) the promotion of oral contraception by the medical and pharmaceutical sectors as the sexual prophylaxis of choice; and (vi) the assumption that HPV vaccines will solve the problem. Here it is proposed that the high prevalence of non-HIV STDs, including distressing disorders such as genital warts and herpes simplex, can be exploited with greater efficacy as a public health deterrent to unsafe sex and HPV transmission. Targeting a "mutually assured infection" campaign at vulnerable subgroups such as teenagers and oral contraceptive users could help reverse the global expansion of HPV-related cancers.

Condoms↗

PubMed2026

Glutathione reductase deficiency potentiates the immunogenicity of ferroptosis and cuproptosis via amplified reactive oxygen species accumulation and cGAS-STING pathway activation.

BACKGROUND: Cancer remains a major therapeutic challenge due to drug resistance and metastasis, processes driven by oxidative stress and redox imbalance. Targeting this vulnerability through ferroptosis (iron-dependent lipid peroxidation) and cuproptosis (copper-driven mitochondrial dysfunction), two ROS-mediated cell death pathways, offers a promising therapeutic strategy. However, clinical translation is hindered by incomplete understanding of their redox regulation and limited immunogenicity. METHODS: A genome-wide CRISPR knockout screen was performed to identify key regulators of ferroptosis. Genetic depletion or pharmacological inhibition of candidate genes was evaluated across multiple cancer cell lines for sensitivity to ferroptosis inducer RSL3 and the cuproptosis inducer elesclomol (Es). Antitumor efficacy was assessed in xenograft, orthotopic, metastatic, and syngeneic mouse models, alone or combined with immune checkpoint inhibitors. Mechanistic studies also examined ROS production, mitochondrial stress, mitochondrial DNA release, cGAS-STING activation, and immune responses within the tumor microenvironment. RESULTS: Glutathione reductase (GSR), a central enzyme maintaining reduced glutathione (GSH) homeostasis, was identified as the top suppressor of ferroptosis. GSR knockout or pharmacological inhibition markedly sensitized diverse cancer cell lines to RSL3-induced ferroptosis, while GSR overexpression conferred resistance. Strikingly, GSR depletion also enhanced sensitivity to cuproptosis triggered by the copper ionophore Es. In multiple in vivo tumor models, GSR inhibition synergizes with RSL3 or Es to suppress tumor growth, inhibit lung metastasis, and prolong survival. Mechanistically, GSR deficiency amplified ROS production, induced mitochondrial stress, and triggered the cytosolic mitochondrial DNA release under ferroptotic or cuproptotic stress, activating the cGAS-STING pathway in vitro and in vivo. This increased inflammatory cytokine production, promoted immunogenic cell death, and enhanced the release of damage-associated molecular patterns (DAMPs), including HMGB1. Together, GSR inhibition combined with a ferroptosis or cuproptosis inducer transformed the tumor microenvironment into a highly immune stimulatory state, thereby enhancing the efficacy of immune checkpoint blockade through increased dendritic cell activation and T-cell infiltration and activation. CONCLUSIONS: GSR represents a key molecular node connecting and modulating ferroptosis and cuproptosis through redox regulation. Targeting GSR amplifies ROS-mediated immunogenic cell death, triggers cGAS-STING activation in cancer cells, and enhances the efficacy of cancer immunotherapy, providing a promising redox-based therapeutic strategy.

Ferroptosis↗

PubMed2003

Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms.

Although all cells in the body require energy to survive and function properly, excessive calorie intake over long time periods can compromise cell function and promote disorders such as cardiovascular disease, type-2 diabetes and cancers. Accordingly, dietary restriction (DR; either caloric restriction or intermittent fasting, with maintained vitamin and mineral intake) can extend lifespan and can increase disease resistance. Recent studies have shown that DR can have profound effects on brain function and vulnerability to injury and disease. DR can protect neurons against degeneration in animal models of Alzheimer's, Parkinson's and Huntington's diseases and stroke. Moreover, DR can stimulate the production of new neurons from stem cells (neurogenesis) and can enhance synaptic plasticity, which may increase the ability of the brain to resist aging and restore function following injury. Interestingly, increasing the time interval between meals can have beneficial effects on the brain and overall health of mice that are independent of cumulative calorie intake. The beneficial effects of DR, particularly those of intermittent fasting, appear to be the result of a cellular stress response that stimulates the production of proteins that enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic factors such as brain-derived neurotrophic factor (BDNF), protein chaperones such as heat-shock proteins, and mitochondrial uncoupling proteins. Some beneficial effects of DR can be achieved by administering hormones that suppress appetite (leptin and ciliary neurotrophic factor) or by supplementing the diet with 2-deoxy-d-glucose, which may act as a calorie restriction mimetic. The profound influences of the quantity and timing of food intake on neuronal function and vulnerability to disease have revealed novel molecular and cellular mechanisms whereby diet affects the nervous system, and are leading to novel preventative and therapeutic approaches for neurodegenerative disorders.

Animals↗

PubMed1999

Persuasion for the purpose of cancer risk reduction: a discussion.

We comment on the preceding papers by Gerrard and Vernon concerning persuasion, perceived risk, and cancer-relevant behavior. Our purpose is to highlight several challenges for future investigators. First, relations between health cognition and health behavior (such as the link between perceived vulnerability and protective behaviors) are likely to be moderated by other variables, including individual differences and situational contexts. Second, we encourage health communication researchers to consider how persuasion is contextualized in social relationships and to employ mechanisms from the literature on social influence when promoting cancer prevention and early detection behaviors. Finally, we emphasize the importance of current feelings and anticipated emotions as motivators of salubrious actions.

Health Promotion↗