Cancer Prevention Research Articles

Coconut Milk Consumption and Breast Cancer Risk in Thai Women: A Case-Control Study

Coconut milk contains plant-based saturated fat and phytochemicals with antioxidant activities. However, its role in breast cancer risk remains unclear. A case-control study was conducted on 244 participants to study the association. The Case group includes 61 newly diagnosed breast cancer patients receiving < 6 months of therapies. The Control group includes 183 healthy people with matched characteristics. A new questionnaire was developed, validated, and used in this study to estimate the frequency of coconut milk-containing food intake. Results show that the questionnaire has satisfactory content validity, test-retest reliability, and criterion-related validity. From the case-control study, either consuming 1–3 or 4–6 times/week of coconut-milk-containing curry or consuming 4–6 times/week of coconut milk-topped desserts are associated with increased risk of breast cancer (OR = 5.23, 5.6, and 2.6 respectively, p < 0.01). Consuming less than half of coconut milk liquid in desserts correlated with a reduced risk (OR = 0.43, p < 0.05). The findings suggest that moderate (less than half of a serving) and infrequent (less than once a week) consumption of coconut milk may be beneficial for breast cancer prevention. A larger scale study is warranted to confirm the findings and provide evidence for dietary recommendations.

Outcomes of medial to lateral vs. lateral to medial approaches in laparoscopic colorectal cancer resections.

Bowel cancer is a significant global health concern, ranking as the third most prevalent cancer worldwide. Laparoscopic resections have become a standard treatment modality for resectable colorectal cancer. This study aimed to compare the clinical and oncological outcomes of medial to lateral (ML) vs lateral to medial (LM) approaches in laparoscopic colorectal cancer resections. A retrospective cohort study was conducted at a UK district general hospital from 2015 to 2019, including 402 patients meeting specific criteria. Demographic, clinical, operative, postoperative, and oncological data were collected. Participants were categorised into LM and ML groups. The primary outcome was 30-day complications, and secondary outcomes included operative duration, length of stay, lymph node harvest, and 3-year survival. A total of 402 patients (55.7% males) were included: 102 (51.6% females) in the lateral mobilisation (LM) group and 280 (58.9% males) in the medial mobilisation (ML) group. Right hemicolectomy (n=157, 39.1%) and anterior resection (n=150, 37.3%) were the most performed procedures. The LM group had a shorter operative time for right hemicolectomy (median 165 vs. 225min, P<0.001) and anterior resection (median 230 vs. 300min, P<0.001). There was no significant difference between the two groups in terms of wound infection (P=0.443), anastomotic leak (P=0.981), postoperative ileus (P=0.596), length of stay (P=0.446), lymph node yield (P=0.848) or 3-year overall survival rate (Log-rank 0.759). The study contributes to the limited evidence on ML vs LM approaches. A shorter operative time in the LM group was noted in this study, contrary to some literature. Postoperative outcomes were comparable, with a non-significant increase in postoperative ileus in the LM group. The study emphasises the safety and feasibility of both approaches.

Association between Bisphenol A and Prostate-Specific Antigen (PSA) among U.S. Older Males: National Health and Nutrition Examination Survey (NHANES), 2003-2012.

There is growing evidence indicating that environmental endocrine disruptors may influence the development of prostate cancer. Despite this, the connection between BPA and PSA levels is still not fully understood and appears intricate. In this study, we aimed to assess the link between BPA exposure and PSA levels using data from the NHANES database. We conducted a weighted linear regression, logistic regression analysis, natural cubic spline (NCS), subgroup analysis, and interaction analysis on 2768 participants. Urinary BPA was considered the independent variable, while PSA was the dependent variable. In the study, the average age of the participants selected was 62.70 years (±12.93). Age was negatively correlated with BPA, while PSA and BMI were positively correlated with BPA concentration (all of the p-value < 0.05). In the fully adjusted model, the weighted linear and logistic regression results showed that BPA was positively correlated with PSA and prostate cancer. NCS analysis results show that BPA and PSA have a non-linear relationship. Sensitivity and subgroup analyses showed similar results. In addition, there were interactions between BPA and age, PIR, education, HbA1c, high-density lipoprotein, smoking status, and Diabetes. There was a positive correlation between urinary BPA and PSA in older American males, especially when the BPA concentration was higher than 4.46 ng/mL. In future practical applications of prostate cancer screening, it is crucial to focus on individuals aged 75 years and older, as well as those with a PIR between 0 and 1, non-Hispanic black, and other risk groups to provide reference values for the primary and secondary prevention of prostate cancer.

Chinese national clinical practice guidelines on prevention, diagnosis and treatment of early colorectal cancer.

The incidence and mortality of colorectal cancer (CRC) in China are increasing in recent years. The clarified pathogenesis and detectable precancerous lesions of CRC make it possible to prevent, screen, and diagnose CRC at an early stage. With the development of endoscopic and surgical techniques, the choice of treatment for early CRC is also worth further discussion, and accordingly, a standard follow-up program after treatment needs to be established. This clinical practice guideline (CPG) was developed following the recommended process of the World Health Organization, adopting Grading of Recommendations Assessment, Development and Evaluation (GRADE) in assessing evidence quality, and using the Evidence to Decision framework to formulate clinical recommendations, thereby minimizing bias and increasing transparency of the CPG development process. We used the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement and Appraisal of Guidelines for Research and Evaluation II (AGREE II) as reporting and conduct guides to ensure the guideline's completeness and transparency. This CPG comprises 46 recommendations concerning prevention, screening, diagnosis, treatment, and surveillance of CRC. In these recommendations, we have indicated protective and risk factors for CRC and made recommendations for chemoprevention. We proposed a suitable screening program for CRC based on the Chinese context. We also provided normative statements for the diagnosis, treatment, and surveillance of CRC based on existing clinical evidence and guidelines. The 46 recommendations in this CPG are formed with consideration for stakeholders' values and preferences, feasibility, and acceptability. Recommendations are generalizable to resource-limited settings with similar CRC epidemiology pattern as China.

Challenges associated with follow-up care after implementation of an HPV screen-and-treat program with ablative therapy for cervical cancer prevention

BackgroundCervical cancer is a preventable cancer; however, decreasing its prevalence requires early detection and treatment strategies that reduce rates of loss to follow-up. This study explores factors associated with loss to follow-up among HPV-positive women after implementation of a new HPV-based screen-and-treat approach for cervical cancer prevention in Iquitos, Peru.MethodsWe conducted semi-structured interviews with “obstetras” (i.e., midwives) (n = 15) working in cervical cancer prevention and women (n = 24) who were recorded as lost to follow-up after positive HPV results. We used the Health Care Access Barriers Model to guide analyses. We utilized manifest content analysis to describe barriers to follow-up according to the obstetras and thematic analysis to report themes from the women’s perspectives. We also report the steps and time taken to contact women.ResultsWe found an incomplete and fragmented patient monitoring system. This incomplete system, in conjunction with challenges in contacting some of the women, led to structural barriers for the obstetras when attempting to deliver positive results. Women in this study expressed a desire to receive treatment, however, faced cognitive barriers including a lack of understanding about HPV results and treatment procedures, fear or anxiety about HPV or treatment, and confusion about the follow-up process. Women also reported having important work matters as a barrier and reported frequently using natural medicine. Reported financial barriers were minimal.ConclusionThis study highlights the barriers to follow-up after implementation of a primary-level HPV-based screen-and-treat approach. While some barriers that have previously been associated with loss to follow-up were not as prominently observed in this study (e.g., financial), we emphasize the need for screen-and-treat programs to focus on strategies that can address incomplete registry systems, structural challenges in results delivery, cognitive barriers in understanding results and treatment, and work-related barriers.

Multidisciplinary advances in kombucha fermentation, health efficacy, and market evolution.

Kombucha, a fermented tea beverage, has seen a significant rise in global popularity. This increase is attributed to its reported health benefits and extensive cultural heritage. The comprehensive review examines kombucha through microbiology, biochemistry, and health sciences, highlighting its therapeutic potential and commercial viability. Central to kombucha production is the symbiotic culture of bacteria and yeasts (SCOBY), which regulates a complex fermentation process, resulting in a bioactive-rich elixir. The study examines the microbial dynamics of SCOBY, emphasizing the roles of various microorganisms. It focuses the contributions of acetic acid bacteria, lactic acid bacteria, and osmophilic yeasts, including genera such as Saccharomyces, Schizosaccharomyces, Zygosaccharomyces, Brettanomyces/Dekkera, and Pichia. These microorganisms play crucial roles in producing bioactive compounds, including organic acids, polyphenols, and vitamins. These bioactive compounds confer therapeutic properties to kombucha. These properties include antioxidant, antimicrobial, anti-inflammatory, antidiabetic, antihypertensive, cancer prevention, hepatoprotective, and detoxifying effects. The review also explores the growing market for kombucha, driven by consumer demand for functional beverages and opportunities for innovative product development. It emphasizes the necessity of standardized production to ensure safety and validate health claims. Identifying research gaps, the review highlights the importance of clinical trials to verify therapeutic benefits. Ultimately, this study integrates traditional knowledge with scientific research, providing directions for future studies and commercial expansion, emphasizing the role of kombucha in health and wellness.

Correlation Between Female Junior High School Students Knowledge And BSE Behaviour

Introduction: Breast cancer often presents as a painless lump and can develop, invade surrounding breast tissue, and spread to nearby lymph nodes or other organs in the body. The high mortality rate of breast cancer is due to a lack of knowledge about the disease and the importance of early detection, leading to many patients seeking medical help at a late stage. According to Globocan data from 2020, teenage cancer patients in Indonesia rank 3rd in Asia. The government recommends Breast Self-Examination (BSE) as the most effective screening method. BSE is very easy to perform, yet many teenagers are unaware of this method. Objective: The review is to summarize the correlation between students knowledge and BSE Behaviour. Method: The study used a descriptive quantitative design with a cross-sectional approach and a simple random sampling technique. The sample size was 141 students, and the chi-square statistical test was used for analysis. Result: The majority, 91.5%, of Ananda Junior High School students had never performed BSE and had poor knowledge about the pathophysiology of breast cancer (93.6%) and breast cancer prevention (83.7%). A p-value of 0.000 (p &lt; 0.05) was obtained, indicating a significant correlation between knowledge about the pathophysiology and prevention of breast cancer and BSE behavior. Conclussion: The proportion of Ananda Bekasi Junior High School students who engage in BSE behavior is very low (8.5%). Most respondents had poor knowledge about the pathophysiology of breast cancer (93.6%) and breast cancer prevention (83.7%).

Application of change-point analysis to HPV infection and cervical cancer incidence in Xinjiang, China in 2011–2019

ObjectiveCervical cancer (CC), serving as a primary public health challenge, significantly threatens women’s health. However, in terms of change-points, there is still a lack of epidemiological studies on the incidence of HPV infection and CC in Xinjiang,China. This research aims to identify significant changes in the trends of HPV infection and CC prevalence in Xinjiang through change-point analysis (CPA) to provide scientific guidance to health authorities.MethodsHPV infection and CC time-series data (from January 2011 to December 2019) were collected and analyzed. Meanwhile, their change-points were detected with binary segmentation method and the PELT method. Furthermore, patients were assigned into three groups based on their different ages and subsequently subjected to an analysis employing a segmented regression model (SRM).ResultsIt was evident that for the monthly HPV time series, the binary segmentation method detected three change points in August 2015, February 2016, and September 2017 (with the most HPV cases). In contrast, the PELT method detected two change-points in September 2015 and April 2017 (with the most HPV cases). For the monthly CC time series, the binary segmentation method identified two change points in October 2012 and August 2019 (with the most CC cases), whereas the PELT method identified three change points in October 2012, August 2019 (with the most CC cases), and October 2019. The SRM demonstrated varying numbers of change points in distinct groups, with HPV infection and CC having the higher growth rate in the 30–49 and 40–59 age groups, respectively. Based on above results, this research was conductive to comprehending the epidemiology of HPV infection and CC in Xinjiang. In addition, it offered scientific guidance for future prevention and management measures for both HPV infection and CC.

Management Approaches for High-Risk Cutaneous Squamous Cell Carcinoma with Perineural Invasion: An Updated Review.

Cutaneous squamous cell carcinoma (cSCC) stands as the second most prevalent non-melanoma skin cancer worldwide, comprising approximately 20% of all cutaneous malignancies. Determining its precise incidence poses challenges; however, reports indicate a global increase in its prevalence. At the time of diagnosis, the majority of cSCCs are localized, resulting in favorable 5-year cure rates surpassing 90%. Nevertheless, a subset of patients (3-7%) encounters locally advanced or metastatic cSCC, leading to substantial morbidity and mortality. The risk of metastasis ranges from 0.1% to 9.9%, carrying an associated mortality risk of 2.8%. Factors influencing recurrence, metastasis, and disease-specific mortality underscore the significance of perineural invasion (PNI) as a key indicator. Patients with PNI may manifest clinical symptoms and/or radiologic signs of PNI, while the majority remain asymptomatic, and PNI is frequently identified upon histologic examination. Despite its lower frequency compared to other cancer types, PNI serves as a recognized adverse prognostic factor for cSCC. Surgery is the elective treatment for these patients, while the role of adjuvant radiotherapy (ART) is yet contentious and have not been conclusively assessed, particularly in clear surgical margin. Prospective comparative studies are required to comprehensively evaluate the benefit and the risks of ART for cSCC and PNI patients.

62 Prognostic biomarker development using deep learning and spatial proteomics in papillary renal cell carcinoma

Abstract Background Papillary renal cell carcinoma (pRCC) is a prevalent but understudied kidney cancer pathology, constituting 15-20% of cases. While many patients achieve curative therapy using nephrectomy, others go on to develop progressive, metastatic disease with poor overall prognosis. In order to improve the current standards of care for pRCC patients, it is critical to identify new methods to identify high-risk patients likely to require more intense and risk-modulated follow-up. Our goals in this project are two-fold: (1) to identify prognostic patient clusters based on spatial architecture of tumor tissue, and (2) to identify a minimal subset of markers to accurately predict the defined clusters for clinical translation. Methods A tissue microarray of 100 pRCC patients was assayed using multiplex immunofluorescence with a 31-antibody panel with immune- and cancer-related proteins. We have developed novel algorithms to identify spatial neighborhoods and features. These features are then used to identify unsupervised clusters of patients. This new approach to classifying patients allows for a more specific and comprehensive description of each patient tumor’s spatial composition and association with diverse clinical outcomes. Next, we developed attention-based deep learning models capable of predicting these spatially-defined clusters directly from the underlying immunofluorescence images and subsequently profiled these for interpretability by retraining based on individual channels. We assessed each model iteratively on a validation set and a held-out test set for final model selection. We focussed on developing an accurate model with the minimal number of channels to enable development of a cost-efficient biomarker assay for the clinic. Results We performed a systematic analysis of the cellular and spatial phenotypes for each patient in our cohort and identified six (6) major spatial clusters. These clusters are based on the spatial neighborhood composition of the tumors (Fig 1A) and describe the composite effects of cell-cell interactions within a patient tumor. We identified one cluster in particular (cluster #6, mainly associated with spatial interaction of CD163+ macrophages) with a significantly worse prognosis than the other clusters. Using our advanced deep learning models, we have been able to achieve excellent validation accuracy in predicting a variety of clinical phenotypes and spatial features, including patient clusters and histological grade. We wished to then reduce the set of required features and began our efforts in predicting tumor vs. normal based on individual immunofluorescence channels and identified 6 channels with &amp;gt;75% individual predictive accuracy (Fig. 1B). Compositing all 6 markers further improves our accuracy to 90%. This success paves the way for exciting future prospects as we work to extend these efforts to identify a minimal clinically-applicable subset of protein markers. Conclusions The combination of computational spatial proteomics and deep learning models has the potential to identify new biomarkers specific to the spatial organization of patient tumors. We have identified a particular patient cluster with multiple associations with CD163+ macrophages demonstrating poor prognosis; selecting these patients may allow for tailored and more informed patient care. We are also working to enhance our deep learning models to circumvent the need for stepwise spatial analysis and, instead, allow for direct-from-image assessment of patients for particular spatial features indicative of various prognostic indicators. Our identified set of 6 markers serves as a basis for further refinements as we work to identify a minimal set of relevant markers able to predict various clinical outcomes from immunofluorescence imaging, offering a promising new avenue in the field of cancer pathology and biomarker development. DOD CDMRP Funding: yes

21 Unconventional mechanisms of action and resistance to rapalogs in renal cancer

Abstract Background Clear cell renal cell carcinoma (ccRCC) is a prevalent cancer type in the United States driven by inactivation of the von Hippel-Lindau (VHL) gene and with frequent hyperactivation of mammalian target of rapamycin complex 1 (mTORC1). Multiple drugs have been developed to target VEGF/VEGFR2 and mTORC1 for advanced RCC treatment. Two specific mTORC1 inhibitors, temsirolimus and everolimus (known as rapalogs), are FDA-approved for the treatment of RCC but their clinical efficacy is hindered by the emergence of resistance. Methods To study the development of rapalog resistance in RCC, we utilized patient-derived tumorgrafts (TGs) implanted in immunocompromised mice and treated the mice with rapamycin for prolonged periods to generate resistance. Resistance was studied by transplanting resistant tumors into additional cohorts of mice and establishing primary cultures. The impact of rapamycin on tumor growth and mTORC1 activity in both tumor and stromal cells was assessed using molecular techniques. To dissect the role of the tumor microenvironment (TME), we generated genetically engineered immunocompromised recipient mice with an mTOR inhibitor resistance mutation (S2035T). Coculture experiments were performed to further explore the interplay. Results Prolonged rapamycin treatment resulted in the development of resistance in TGs. Notably, this occurred despite persistent inhibition of mTORC1 in tumor cells. Resistance was transient and lost with subsequent transplantation and in cell culture. Surprisingly, resistance was accompanied by mTORC1 reactivation in the TME, specifically in cancer associated fibroblasts. Introducing an mTOR resistance mutation (S2035T) into recipient mice was sufficient to cause resistance. Co-culture experiments with fibroblasts further demonstrated that rapamycin-resistant mutant fibroblasts conferred resistance in tumor cells even in the absence of mTORC1 activity. Conclusions This study uncovers a critical role of the TME, in mediating the response and resistance to rapalogs in RCC. Our data show that inhibition of mTORC1 in non-tumor cells is essential for the anti-tumor activity of rapalogs. These findings shed light on why mTOR mutations are rarely observed in resistant RCC patients and highlight the significance of the TME in modulating drug response and resistance. Moreover, our study emphasizes the potential of targeting TME cells as a therapeutic strategy in RCC and possibly other cancers. DOD CDMRP Funding: yes

A computational approach for screening of phytochemicals from Oxalis corniculata as promising anti-cancer candidates

Objectives.In silico techniques are a highly efficient, cost-effective, and rapid approach to identify potent herbal lead compounds with therapeutic potential against cancer. Phytochemicals are abundant in plants and may represent a promising cancer prevention and treatment approach. The plant species Oxalis corniculata has long been employed in traditional medicine to treat various diseases. Indeed, previous studies have demonstrated the anti-cancer properties of the crude extract obtained from this plant. However, further research is essential to elucidate precisely the underlying molecular mechanisms responsible for these activities.Methods.The study investigated the potential of bioactive compounds from O. corniculata to bind with different targets of anti-cancer drugs. Employing molecular docking and drug-likeness, 19 bioactive compounds from the plant were tested as potential anti-cancer leads. Compounds that exhibit both favorable drug-likeness and binding energies comparable to those of standard drugs like curcumin, doxorubicin, and paclitaxel were selected for further evaluation of their pharmacokinetic properties.Results and Conclusions.Among the 19 selected phytoconstituents of O. corniculata, compounds 15 and 16 exhibited the most effective binding energy (−8.68, −8.22 and −8.70, −8.22, −8.52 kcal/mol, respectively) with key cancer targets including Programmed death-ligand 1 (PDB: 7bea), B-Raf proto-oncogene, serine/threonine kinase (PDB: 8c7y) and poly (ADP-ribose) polymerase (PDB: 7kk4). Pharmacokinetic and toxicity analysis provided additional insights into the potential of these compounds as anti-cancer drugs. The computational analysis holds promise in accelerating the development of novel drug therapies aimed at treating various cancer types.

The rational design of cervical cancer prevention strategies

The rational design of cervical cancer prevention strategies

Unveiling the Bioactive Efficacy of Cupressus sempervirens 'Stricta' Essential Oil: Composition, In Vitro Activities, and In Silico Analyses.

Prior studies have extensively investigated the essential oil derived from the Mediterranean cypress, Cupressus sempervirens. However, the 'Stricta' variety, known for its ornamental value, has received less attention in terms of its oil composition and potential health benefits. The objective of this research was to comprehensively analyze the chemical components and medicinal properties of the essential oil extracted from C. sempervirens 'Stricta' (CSSLEO) grown in Egypt. Utilizing gas chromatography-mass spectrometry (GC-MS), the investigation identified 22 compounds within CSSLEO, with α-pinene and δ-3-carene being predominant, accounting for 96.01% of the oil. In vitro assays evaluated CSSLEO's cytotoxic effects on cancer cell lines, revealing notable anticancer potential. Additionally, the oil displayed antidiabetic properties by impeding crucial enzymes involved in glucose metabolism. Complementary in silico network pharmacology and molecular docking studies provided insights into the possible interactions between CSSLEO's key compounds and essential proteins and pathways in cancer treatment. The results underscored CSSLEO's intricate composition and its promising applications in cancer prevention and diabetes management. The conclusions drawn from this research underscore the need for further investigation to validate CSSLEO's clinical effectiveness and to gain a deeper understanding of its therapeutic mechanisms, with a view to harnessing its potential in oncology and endocrinology.

Differentially localized protein identification for breast cancer based on deep learning in immunohistochemical images

The mislocalization of proteins leads to breast cancer, one of the world’s most prevalent cancers, which can be identified from immunohistochemical images. Here, based on the deep learning framework, location prediction models were constructed using the features of breast immunohistochemical images. Ultimately, six differentially localized proteins that with stable differentially predictive localization, maximum localization differences, and whose predicted results are not affected by removing a single image are obtained (CCNT1, NSUN5, PRPF4, RECQL4, UTP6, ZNF500). Further verification reveals that these proteins are not differentially expressed, but are closely associated with breast cancer and have great classification performance. Potential mechanism analysis shows that their co-expressed or co-located proteins and RNAs may affect their localization, leading to changes in interactions and functions that further causes breast cancer. They have the potential to help shed light on the molecular mechanisms of breast cancer and provide assistance for its early diagnosis and treatment.

In Situ Colorimetric LAMP Based on One-Step Modified Filter Paper to Screen Human Papillomavirus (HPV)16/18 from Clinical Samples.

Cervical cancer is among the most common malignant tumors in women. The development of rapid screening techniques plays an important role in early screening for cancer treatment. We have developed an HPV screening method, which effectively combines the high-efficiency nucleic acid enrichment of chitosan-modified filter paper and the rapid visual detectability of colorimetric LAMP, along with the enhancement of the tolerance ability of the pH-sensitive LAMP reagent to acidic original samples, making the detection of HPV 16/18 easy to carry out and reliable, which is helpful for the epidemiological prevention and control strategies of HPV-induced cancer. This technique can simultaneously exhibit the "in situ amplification" capability of chitosan-modified filter paper and the nontemperature cycle dependence of visual LAMP detection. Therefore, DNA extraction and amplification can be performed efficiently and quickly within a single reaction where all DNA is concentrated in the QF paper disc. By embedding amino-modified filter paper into the plastic chip, a simple and reliable disposable chip was prepared for rapid HPV16 and HPV18 detection from clinical endometrial samples, and the results were 100% consistent with clinical diagnosis. More importantly, even after the sample was diluted 100-fold, HPV16/18-infected cells could be accurately identified, showing the advantages of the system in early cancer screening. Moreover, for endometrial samples containing plenty of cells, the filter paper could be used to enrich cells by filtration, preventing the acidic fluid from impacting pH-induced colorimetric LAMP detection and realizing direct amplification for HPV identification without nucleic acid extraction. This easy-to-operate system that can analyze a wide range of samples will be suitable for routine on-site HPV screening, dramatically extending the applications and utility for rapid, near-patient nucleic acid testing.

Blood Leukocyte DNA Methylation Markers of Periodontal Disease and Risk of Lung Cancer in a Case-Control Study Nested in the CLUE II Cohort.

Periodontal disease and DNA methylation markers have separately been associated with lung cancer risk. Examining methylation levels at genomic regions previously linked to periodontal disease may provide insight on the link between periodontal disease and lung cancer. In a nested case-control study drawn from the CLUE II cohort, we measured DNA methylation levels in 208 lung cancer cases and 208 controls. We examined the association between 37 DNA methylated CpG sites at three genomic regions, Homeobox 4 (HOXA4), Zinc finger protein (ZFP57) and a lcRNA gene region located in Chr10 (ENSG00000231601), and lung cancer risk. Statistically significant associations with lung cancer risk were observed for all 14 CpG sites from HOXA4 (odds ratio [OR] ranging 1.41-1.62 for 1 SD increase in methylation level, especially within 15 years) and one CpG site on gene ENSG00000231601 (OR=1.34 for 1 SD increase in DNA methylation level). While CpG sites on gene ZFP57 were not associated with lung cancer risk overall, statistically significant inverse associations were noted for six CpGs when restricting follow-up to 15 years (OR=0.73-0.77 for 1 SD increase in methylation level). Key methylation changes associated with periodontal disease are also associated with lung cancer risk. For both HOXA4 and ZFP57, that these associations were stronger within 15 years of follow up suggests that they act late in the natural history of lung cancer. Identifying biological pathways that link periodontal disease and lung cancer could provide new opportunities for lung cancer detection and prevention.

Biohybrid hydrogel inhibiting β-klotho/HDAC3 axis for hepatocellular carcinoma treatment

Hepatocellular carcinoma (HCC), ranking as the fourth most prevalent cancer globally, has garnered significant attention due to its high invasiveness and mortality rates. However, drug therapies face challenges of inadequate efficacy and unclear mechanisms. Here, we propose a novel biohybrid hydrogel that targets β-klotho (KLB) for HCC treatment. As a dual-network hydrogel, this gel combines gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA) to ensure biocompatibility while enhancing controlled drug release. Notably, it exhibits good storage stability, high drug load capacity, and efficient water absorption. By introducing the HDAC3 inhibitor RGFP966, we can selectively inhibit the activation of KLB. This deactivation effectively blocks the FGF21-KLB signaling pathway and inhibits the progression of HCC. Importantly, we have successfully validated this unique phenomenon both in vivo and in vitro, providing substantial evidence for the efficacy of this hydrogel-based anti-tumor drug delivery system as a promising strategy for HCC treatment. This innovative research outcome brings new hope to the field of tumor therapy, providing a reliable theoretical foundation for future clinical applications.

Decreased Long-Term Survival of Patients With Newly Diagnosed Cancer Discharged Home After Unplanned ICU Admission: A Prospective Observational Study.

To compare the 18-month survival between patients with newly diagnosed cancer discharged home after early unplanned ICU admission and those without early unplanned ICU admission; we also evaluated the frequency and risk factors for early unplanned ICU admission. Observational study with prospectively collected data from September 2019 to June 2021 and 18 months follow-up. Single dedicated cancer center in São Paulo, Brazil. We screened consecutive adults with suspected cancer and included those with histologically proven cancer from among 20 highly prevalent cancers. None. The exposure was early unplanned ICU admission, defined as admission for medical reasons or urgent surgery during the first 6 months after cancer diagnosis. The main outcome was 18-month survival after cancer diagnosis, and the main analysis was Cox's proportional hazards model adjusted for confounders and immortal time bias. Propensity score matching was used in the sensitivity analysis. We screened 4738 consecutive adults with suspected cancer and included 3348 patients. Three hundred twelve (9.3%) had early unplanned ICU admission, which was associated with decreased 18-month survival both in the unadjusted (hazard ratio, 4.03; 95% CI, 2.89-5.62) and adjusted (hazard ratio, 1.84; 95% CI, 1.29-2.64) models. The sensitivity analysis confirmed the results because the groups were balanced after matching, and the 18-month survival of patients with early ICU admission was lower compared with patients without early ICU admission (87.0% vs. 93.9%; p = 0.01 log-rank test). Risk factors for early unplanned ICU admission were advanced age, comorbidities, worse performance status, socioeconomic deprivation, metastatic tumors, and hematologic malignancies. Patients with newly diagnosed cancer discharged home after early unplanned ICU admission have decreased 18-month survival compared with patients without early unplanned ICU admission.

The Co-Production, Pilot and Qualitative Evaluation of a Cancer Prevention Programme With High-Risk Women Delivered on Group Walks by Cancer Champions: Shoulder to Shoulder, Walk and Talk.

Women in the criminal justice system and women who have been subject to domestic abuse are at high risk of cancer but underrepresented in health promotion research. We aimed to co-produce, pilotand evaluate a health promoting programme delivered on group walks. A programme co-produced by women, based on motivational interviewing, created the opportunity for supportive conversations about cancer prevention. Programme development in two workshops with women with lived experience using authentic vignettes to prompt help-seeking conversations. A small pilot and a qualitative evaluation was done using framework analysis. The programme appeared acceptable to women and the walk leaders. Women felt included and found it a safe space for sensitive conversations. They appeared empowered and more confident to seek help. Walk leaders expressed confidence in delivering this informal programme, which used prompts rather than delivering didactic training. Cancer prevention for high-risk groups can be delivered in a personalised and novel way by creating informal opportunities for supportive conversations about cancer prevention. Careful co-production of the programme of walks with women, using scenarios and quotes that were authentic vignettes, ensured that these came directly from the women's lived experience and enabled women to talk about change. Our findings indicate that this approach was practical, relevant and acceptable to them with some evidence of women feeling empowered to make informed decisions about their health. We recommend that future cancer prevention programmes for underrepresented groups take an asset-based approach by utilising pre-existing community organisations to increase reach and sustainability. Women with lived experience co-designed and tested the programme. Provisional findings were fed back to the women and the women's organisation that partnered with this research.