BMC Cancer最新文献

Background: The relationship between sleep traits and survival in breast cancer is uncertain and complex. There are multiple biological, psychological and treatment-related factors that could link sleep and cancer outcomes. Previous studies could be biased due to methodological limitations such as reverse causation and confounding. Here, we used two-sample mendelian randomisation (MR) to investigate the causal relationship between sleep and breast cancer mortality.

Methods: Publicly available genetic summary data from females of European ancestry from UK Biobank and 23andme and the Breast Cancer Association Consortium were used to generate instrumental variables for sleep traits (chronotype, insomnia symptoms, sleep duration, napping, daytime-sleepiness, and ease of getting up (N = 446,118-1,409,137)) and breast cancer outcomes (15 years post-diagnosis, stratified by tumour subtype and treatment (N = 91,686 and Ndeaths = 7,531 over a median follow-up of 8.1 years)). Sensitivity analyses were used to assess the robustness of analyses to MR assumptions.

Results: Initial results found some evidence for a per category increase in daytime-sleepiness reducing overall breast cancer mortality (HR = 0.34, 95% CI = 0.14, 0.80), and for insomnia symptoms reducing odds of mortality in oestrogen receptor positive breast cancers not receiving chemotherapy (HR = 0.18, 95% CI = 0.05, 0.68) and in patients receiving aromatase inhibitors (HR = 0.23, 95% CI = 0.07, 0.78). Importantly, these relationships were not robust following sensitivity analyses meaning we could not demonstrate any causal relationships.

Conclusions: This study did not provide evidence that sleep traits have a causal role in breast cancer mortality. Further work characterising disruption to normal sleep behaviours and its effects on tumour biology, treatment compliance and quality of life are needed.

Docetaxel is a widely used first-line treatment for castration-resistant prostate cancer (CRPC). RhoB, a member of the Rho GTPase family, plays a major role in prostate cancer metastasis by modulating the PI3K-AKT signaling pathway. It is crucial in regulating cytoskeletal reassembly, cell migration, focal adhesion (FA) dynamics. To investigate RhoB's function in prostate cancer, CRISPR/Cas9 gene editing technique was utilized to knock out the RhoB gene in prostate cancer cells. Successful gene editing was confirmed by using T7 endonuclease I (T7EI) assays and Sanger sequencing. Knocking out RhoB enhanced epithelial-mesenchymal transition (EMT) and decreased the IC50 value of docetaxel in RhoB-knockout PC-3 cells. This suggests increased sensitivity to docetaxel. Furthermore, RhoB knockout prompted the migration and invasion of prostate cancer cells, effects that were reversed upon RhoB overexpression. Interestingly, RhoB status did not significantly influence the cell cycle of prostate cancer cells. RNA sequencing of PC-3 cells with either overexpressed or knock-out RhoB revealed that RhoB regulates pathways involved in FA, ECM receptor interaction, and PI3K-AKT signaling. These pathways directly influence the EMT process, cell migration, and invasion in prostate cancer cells. Notably, RhoB overexpression activated PI3K-AKT signaling when PC-3 cells were treated with low concentration of DTXL (50 nM, 72 h). This activation reduced DTXL's cytotoxicity, suggesting may confer chemoresistance via PI3K-AKT pathway activation.

Background: Ovarian cancer (OC) poses a significant threat to women's health due to its insidious onset, tendency to metastasize, and high recurrence rate. These characteristics significantly impede early diagnosis and effective interventions. The current lack of effective screening and prognostic tools necessitates urgent solutions. The Shanghai Ovarian Cancer and Family Care Project (SOCFCP) is an ongoing cohort study aiming to address these challenges by identifying factors and biomarkers associated with OC onset, treatment, and prognosis. The ultimate goal is to develop predictive models and assessments crucial for diagnosing, treating, and prognosing the disease.

Methods: During the study period from 2023 to 2028, the SOCFCP aims to recruit over 2000 patients with ovarian lesions, 900 high-risk individuals, and 3000 healthy controls in Shanghai, China, with long-term follow-up. The study comprises three cohorts: (1) a bidirectional patients cohort, comprising those diagnosed with ovarian disease and treated at the department of gynecologic oncology at Shanghai first maternity and infant hospital since 2013; (2) a prospective high-risk cohort, consisting of family members of ovarian and/or breast cancer patients, or individuals with related gene mutations; and (3) a healthy control cohort, drawn from women undergoing health examination at hospitals or participating in community gynecologic cancer screenings. Participants will attend regular visits for questionnaire surveys, anthropometric measurements, and the collection of biological specimens, such as blood, fecal, and tissue samples. Collected data encompass baseline information, sociodemographic details, hospital admission records, and biological and clinical parameters, alongside treatment information. Primary outcomes for the patient cohort include mortality, tumor recurrence, major complications, and changes in health-related quality of life post-diagnosis. For the high-risk and healthy cohorts, ovary-related diseases will serve as the primary outcome. Various predictive models, such as multivariate logistic models, Cox regression, and linear mixed-effects regression models, will be employed to analyze various endpoints appropriately.

Discussion: This extensive cohort study integrates a diverse range of information, including lifestyle factors, environmental influences, genetic characteristics, and clinical features, alongside an extensive collection of biological samples. The resources generated by this project will provide valuable foundations for a comprehensively understanding of the etiology, treatment, and prognosis of OC. The SOCFCP is poised to foster cutting-edge multidisciplinary research on OC, spanning both fundamental and clinical studies.

Trial registration: NCT06118307 in ClinicalTrials.gov. Registration Date: November 7, 2023.

Background: The existing anticancer drugs in clinical practice show poor efficacy in cervical cancer patients and are associated with multiple side effects. Our previous study demonstrated the strong antineoplastic activity of crude extract prepared from the stem bark of Azadirachta indica (Neem) against cervical cancer. However, the active phytoconstituents of neem stem bark extract and its underlying anticancer mechanism are yet to be investigated. Thus, the present study aimed to identify the active fraction from crude neem stem bark extract to further dissect its anticancer mechanism and determine the active components.

Methods: Dichloromethane (DCM) extract from neem stem bark was prepared and fractionated using thin-layer chromatography. The fractions obtained were screened against HeLa and ME-180 cervical cancer cell lines to identify the most active fraction, which was then selected for further studies. Clonogenic assay, cell cycle analysis, apoptosis assay, and reactive oxygen species (ROS) assay were performed to determine the cytotoxicity of the active fraction. Gene expression was analyzed using real-time PCR and western blot to determine the mechanism. Additionally, the HeLa cells-derived 3D spheroid model was used to determine the antitumor efficacy of the active fraction. Electrospray ionization-mass spectrometry, Fourier-transform infrared spectroscopy, and proton nuclear magnetic resonance were used to identify the phytoconstituents of the fraction.

Results: Initial screening revealed fraction 2 (F2) as the most active fraction. Additionally, F2 showed the least cytotoxic effect on normal human fibroblast cells. Mechanistically, F2 induced cell cycle arrest and apoptosis in cervical cancer cells. F2 increased ROS levels, induced ER stress, and activated cell survival pathway. Treatment with N-acetyl cysteine revealed that F2 induced ROS-independent ER stress and apoptosis. 3D spheroid viability and growth delay experiments demonstrated the strong antitumor potential of F2. Finally, six compounds, including one flavonoid (nicotiflorin) and five limonoids, were identified in the F2 fraction.

Conclusion: This is the first study to identify the active fraction and its phytoconstituents from neem stem bark and demonstrate the anticancer mechanism against cervical cancer. Our study highlights the importance of investigating neem stem bark-derived limonoids and nicotiflorin as a potential source to develop new anticancer therapeutic agents.

Background: Patients with a rare cancer in rural, regional, and remote Australia experience heightened challenges in their illness journey, including significant psychosocial impacts. Although peer support has shown benefits for common cancer patients living in urban areas, these programs often do not reach underserved groups for instance those with a rare cancer, or those living in rural, regional or remote areas. This study aimed to explore the characteristics of peer support programs for patients with a rare cancer living in rural, regional or remote areas.

Methods: Focus groups and interviews were conducted with 39 people with a rare cancer and 10 healthcare providers to explore key points for inclusion in a peer support service for people diagnosed with a rare cancer living in rural, regional or remote areas. Data were transcribed verbatim and analysed thematically, using Nvivo.

Results: Participants described their peer support needs using the key terms who, what, how, where, and when. Participants advocated for a flexible, multicomponent intervention that could meet the varied and fluctuating needs of this group. Participants also noted challenges with the practical delivery of such a service, specifically, the risk of receiving misinformation, adverse emotional reactions, interpersonal challenges and implementation issues.

Conclusions: This study highlights the role of peer support in addressing unmet needs of patients with a rare cancer, particularly in rural areas, emphasising the importance of tailored, flexible, and multimodal interventions for the delivery of peer support that addresses diverse needs.

Background: Adolescent and young adult (AYA) patients with cancer experience complex physical and psychosocial development as well as diverse lifestyle changes. Therefore, each patient may have generation-specific needs. This study aimed to develop a Japanese version of the Cancer Needs Questionnaire-Young People (CNQ-YP), namely the CNQ-YP-J, and to verify its reliability and validity among Japanese AYA patients with cancer.

Methods: The CNQ-YP-J was developed using a standardized translation methodology. Content validity was assessed by a group of experts, and a pilot test was conducted with six AYA cancer patients. A total of 87 AYA patients with cancer participated in this study. After exploratory factor analysis, the scale's reliability was examined using Cronbach's α, item-total correlations, and the intraclass correlation coefficient (ICC) of the retest. Criterion-related validity was analysed using correlations between total needs, concerns about physical effects, and quality of life (QOL).

Results: The factor analysis revealed an eight-factor structure, different from the original scale, with one item excluded, resulting in a 69-item scale. Cronbach's α coefficient and ICC were above the minimum acceptable criterion of 0.70, demonstrating high reliability. Concerning criterion-related validity, high needs were positively correlated with high concerns about physical effects and negatively correlated with QOL.

Conclusions: The CNQ-YP-J developed in this study is a reliable and potentially valid scale that comprehensively assesses the needs of AYA cancer patients in the treatment environment as well as their daily lives. We hope that the use of this scale as a measure of the needs of AYA cancer patients in various settings, including clinical practice, will lead to the provision of optimal medical care and development of support systems, as well as the promotion of information.

Background: Discrepancies have been found between preoperative colposcopic biopsy results and histology results of loop electrical excision procedure (LEEP) specimens. GynTect^® is a six-methylation-marker assay that has demonstrated its potential as a triage tool for cervical lesion detection and prediction. The aim of this study was to evaluate the effectiveness of GynTect^® in predicting the histology outcomes of post-LEEP specimens.

Method: A retrospective analysis was conducted to evaluate the clinical profiles, GynTect^® results, and histology outcomes of postoperative specimens from 78 patients diagnosed with high-grade squamous intraepithelial lesion (HSIL) who underwent LEEP. The GynTect^® assay is a six-marker (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671) methylation detection assay for cervical prep cell samples. Preoperative cervical cytology, high-risk human papillomavirus (hrHPV) detection, and methylation analysis were obtained from each participant. Preoperative colposcopic impression and biopsy results were recorded. Statistical analysis and multivariate logistic regression were performed using IBM SPSS Statistics 25.

Results: Among the negative-GynTect^® patients, 19 cases (57.6%) showed histology downgrading post-LEEP, while 14 cases (42.4%) showed sustained or upgrading histology results. In the positive-GynTect^® patients, 8 cases (17.8%) showed downgrading histology results post-LEEP and 37 cases (82.2%) showed sustained or upgrading histology. The difference was statistically significant (p = 0.001). Multivariate regression analysis identified positive GynTect^® outcomes and colposcopic impressions indicating HSIL on the day of surgery as independent predictors of pathological sustained or upgrading after LEEP.

Conclusions: This study underscores the potential of GynTect^® in predicting histology outcomes of post-LEEP specimens, thereby showcasing its promising ability to assist clinicians in selecting appropriate therapeutic regimens for patients with HSIL.

Background: Emerging research suggested a potential role of immune cells in colorectal cancer (CRC) development. However, the causal relationship between immune phenotypes and CRC remains elusive. Hence, this two-sample Mendelian randomization (MR) study aimed to explore the causal association.

Methods: In this study, a bidirectional, two-sample MR analysis and multivariate MR was conducted, leveraging public genetic data. Four types of immune phenotypes were employed. A comprehensive sensitivity analysis was carried out to validate the robustness, heterogeneity, and horizontal pleiotropy of the results, with Bonferroni correction applied for accurate interpretation.

Results: It was revealed that four immune cell phenotypes were significantly associated with CRC risk. Specifically, lymphocyte % leukocyte in the T-cell/B-cell/NK-cell (TBNK) group (odds ratio (OR) = 1.0013, 95% confidence interval (CI): 1.0005-1.0017, P = 0.0003, P_Bonferroni = 0.011) and CD3 on CM CD8br in the maturation stages of T cell group (OR = 1.0014, 95% CI: 1.0006-1.0022, P = 0.0007, P_Bonferroni = 0.023) were positively correlated with the risk of CRC. Conversely, DN (CD4^-CD8^-) %leukocyte in the TBNK group (OR = 0.9990, 95% CI: 0.9984-0.9997, P = 0.0020, P_Bonferroni = 0.063) and herpesvirus entry mediator (HVEM) on CD8br in the maturation stages of T cell group (OR = 0.9989, 95% CI: 0.9982-0.9997, P = 0.00431, P_Bonferroni = 0.137) exhibited a negative association with the risk of CRC. This study did not detect any statistically significant impact of CRC on immune phenotypes.

Conclusions: This study inferred an association between immune cells and CRC risk. Nevertheless, further clinical and experimental studies are warranted to validate these findings and elucidate the underlying mechanisms.

Background: Cancer survivors may experience accelerated biological aging, increasing their risk of mortality. However, the association between phenotypic age acceleration (PAA) and mortality among cancer survivors remains unclear. This study aimed to evaluate the relationship between PAA and all-cause mortality, cancer-specific mortality, and non-cancer mortality among adult cancer survivors in the United States.

Methods: We utilized data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, including 2,643 (unweighted) cancer patients aged ≥ 20 years. Phenotypic age was calculated using ten physiological biomarkers, and the residuals from regressing phenotypic age on chronological age (age acceleration residuals, AAR) were used to determine PAA status. Participants were divided into PAA and without PAA groups based on the sign of the residuals. Weighted Cox proportional hazards regression models were used to assess the association between PAA and mortality, adjusting for demographic characteristics, lifestyle factors, and comorbidities. Restricted cubic spline (RCS) models were employed to explore the dose-response relationship between AAR and mortality.

Results: Over a median follow-up of 9.16 years, 991 (unweighted) participants died. After adjusting for multiple covariates, PAA was significantly associated with increased risks of all-cause mortality (HR = 2.07; 95% CI: 1.69-2.54), cancer-specific mortality (HR = 2.15; 95% CI: 1.52-3.04), and non-cancer mortality (HR = 2.06; 95% CI: 1.66-2.57). Each one-unit increase in AAR was associated with a 4% increase in the risk of all-cause, cancer-specific, and non-cancer mortality (HR = 1.04; 95% CI: 1.03-1.05). RCS models indicated a linear dose-response relationship between AAR and mortality.

Conclusions: Among U.S. adult cancer survivors, PAA is significantly associated with all-cause, cancer-specific, and non-cancer mortality. PAA may serve as an important biomarker for predicting prognosis in cancer survivors.

Background: Sarcopenia in patients with non-small cell lung cancer (NSCLC) is often indicative of a more aggressive disease course and a poorer prognosis. Nevertheless, there have been limited studies that specifically examined clinical parameters to predict sarcopenia in individuals with malignant pleural effusion (MPE). Our objective is to investigate the potential correlations between commonly utilized clinical variables and reduced muscle mass in NSCLC patients who also have MPE.

Methods: This retrospective study examined the clinicopathological data and imaging characteristics of NSCLC patients admitted to the hospital with MPE. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was employed to select the most appropriate variables for model creation, effectively reducing the chance of overfitting. Logistic regression analysis was conducted to pinpoint the independent factors predicting sarcopenia in NSCLC patients with MPE. Subsequently, a nomogram was formulated to estimate the sarcopenia risk for individual patient. The efficacy of this nomogram was assessed through various metrics, including the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).

Results: A total of 139 patients, with an average age of 66 years and a majority being male (56.8%), were included in this study. Multivariate logistic regression analysis revealed that age, body mass index (BMI), albumin (Alb), and cytokeratin-19-fragment (CY21-1) were all independent predictors of sarcopenia in NSCLC patients with MPE. A nomogram was developed to facilitate personalized prediction of sarcopenia for individual patient. The ROC curve demonstrated that the nomogram model incorporating these predictive factors achieved an area under the curve (AUC) of 0.889, indicating its discriminatory power in predicting sarcopenia. The calibration curve demonstrated a strong concordance between the actual and the anticipated sarcopenia risk. DCA further confirmed that the nomogram showed good clinical applicability and net benefits in sarcopenia prediction.

Conclusions: Certain commonly used clinical characteristics were found to be associated with decreased skeletal muscle mass. Specifically, age, BMI, Alb, and CY21-1 levels emerged as predictive indicators for sarcopenia among NSCLC patients with MPE. These indicators have the potential to serve as effective alternatives to traditional computed tomography (CT) evaluation in assessing sarcopenia.