Impact of cancer diagnosis on life expectancy by area-level socioeconomic groups in New South Wales, Australia: a population-based study.

OBJECTIVE: Improvement in cancer survival over recent decades has not been accompanied by a narrowing of socioeconomic disparities. This study aimed to quantify the loss of life expectancy (LOLE) resulting from a cancer diagnosis and examine disparities in LOLE based on area-level socioeconomic status (SES). METHODS: Data were collected for all people between 50 and 89 years of age who were diagnosed with cancer, registered in the NSW Cancer Registry between 2001 and 2019, and underwent mortality follow-up evaluations until December 2020. Flexible parametric survival models were fitted to estimate the LOLE by gender and area-level SES for 12 common cancers. RESULTS: Of 422,680 people with cancer, 24% and 18% lived in the most and least disadvantaged areas, respectively. Patients from the most disadvantaged areas had a significantly greater average LOLE than patients from the least disadvantaged areas for cancers with high survival rates, including prostate [2.9 years (95% CI: 2.5-3.2 years) vs. 1.6 years (95% CI: 1.3-1.9 years)] and breast cancer [1.6 years (95% CI: 1.4-1.8 years) vs. 1.2 years (95% CI: 1.0-1.4 years)]. The highest average LOLE occurred in males residing in the most disadvantaged areas with pancreatic [16.5 years (95% CI: 16.1-16.8 years) vs. 16.2 years (95% CI: 15.7-16.7 years)] and liver cancer [15.5 years (95% CI: 15.0-16.0 years) vs. 14.7 years (95% CI: 14.0-15.5 years)]. Females residing in the least disadvantaged areas with thyroid cancer [0.9 years (95% CI: 0.4-1.4 years) vs. 0.6 years (95% CI: 0.2-1.0 years)] or melanoma [0.9 years (95% CI: 0.8-1.1 years) vs. 0.7 years (95% CI: 0.5-0.8 years)] had the lowest average LOLE. CONCLUSIONS: Patients from the most disadvantaged areas had the highest LOLE with SES-based differences greatest for patients diagnosed with cancer at an early stage or cancers with higher survival rates, suggesting the need to prioritise early detection and reduce treatment-related barriers and survivorship challenges to improve life expectancy.

Advances in Bacterial Lysate Immunotherapy for Infectious Diseases and Cancer.

Antigenic cell fragments, pathogen-associated molecular patterns, and other immunostimulants in bacterial lysates or extracts may induce local and systemic immune responses in specific and nonspecific paradigms. Based on current knowledge, this review aimed to determine whether bacterial lysate has comparable functions in infectious diseases and cancer treatment. In infectious diseases, including respiratory and urinary tract infections, immune system activation by bacterial lysate can identify and combat pathogens. Commercially available bacterial lysates, including OM-85, Ismigen, Lantigen B, and LW 50020, were effective in children and adults in treating respiratory tract infections, chronic obstructive pulmonary disease, rhinitis, and rhinosinusitis with varying degrees of success. Moreover, OM-89, Uromune, Urovac, Urivac, and ExPEC4V showed therapeutic benefits in controlling urinary tract infections in adults, especially women. Bacterial lysate-based therapeutics are safe, well-tolerated, and have few side effects, making them a good alternative for infectious disease management. Furthermore, a nonspecific immunomodulation by bacterial lysates may stimulate innate immunity, benefiting cancer treatment. "Coley's vaccine" has been used to treat sarcomas, carcinomas, lymphomas, melanomas, and myelomas with varying outcomes. Later, several similar bacterial lysate-based therapeutics have been developed to treat cancers, including bladder cancer, non-small cell lung cancer, and myeloma; among them, BCG for in situ bladder cancer is well-known. Proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, may activate bacterial antigen-specific adaptive responses that could restore tumor antigen recognition and response by tumor-specific type 1 helper cells and cytotoxic T cells; therefore, bacterial lysates are worth investigating as a vaccination adjuvants or add-on therapies for several cancers.

An mRNA vaccine for pancreatic cancer designed by applying in silico immunoinformatics and reverse vaccinology approaches.

Pancreatic ductal adenocarcinoma is the most prevalent pancreatic cancer, which is considered a significant global health concern. Chemotherapy and surgery are the mainstays of current pancreatic cancer treatments; however, a few cases are suitable for surgery, and most of the cases will experience recurrent episodes. Compared to DNA or peptide vaccines, mRNA vaccines for pancreatic cancer have more promise because of their delivery, enhanced immune responses, and lower proneness to mutation. We constructed an mRNA vaccine by analyzing S100 family proteins, which are all major activators of receptors for advanced glycation end products. We applied immunoinformatic approaches, including physicochemical properties analysis, structural prediction and validation, molecular docking study, in silico cloning, and immune simulations. The designed mRNA vaccine was estimated to have a molecular weight of 165023.50 Da and was highly soluble (grand average of hydropathicity of -0.440). In the structural assessment, the vaccine seemed to be a well-stable and functioning protein (Z score of -8.94). Also, the docking analysis suggested that the vaccine had a high affinity for TLR-2 and TLR-4 receptors. Additionally, the molecular mechanics with generalized Born and surface area solvation analysis of the "Vaccine-TLR-2" (-141.07 kcal/mol) and "Vaccine-TLR-4" (-271.72 kcal/mol) complexes also suggests a strong binding affinity for the receptors. Codon optimization also provided a high expression level with a GC content of 47.04% and a codon adaptation index score 1.0. The appearance of memory B-cells and T-cells was also observed over a while, with an increased level of helper T-cells and immunoglobulins (IgM and IgG). Moreover, the minimum free energy of the mRNA vaccine was predicted at -1760.00 kcal/mol, indicating the stability of the vaccine following its entry, transcription, and expression. This hypothetical vaccine offers a groundbreaking tool for future research and therapeutic development of pancreatic cancer.

Association of optimism and social support with health-related quality of life among Australian women cancer survivors - A cohort study.

AIM: Large-scale studies investigating health-related quality of life (HRQL) in cancer survivors are limited. This study aims to investigate HRQL and its relation to optimism and social support among Australian women following a cancer diagnosis. METHODS: Data were from the Australian Longitudinal Study on Women's Health, a large cohort study (n = 14,715; born 1946-51), with 1428 incident cancer cases ascertained 1996-2017 via linkage to the Australian Cancer Database. HRQL was measured using the Short Form-36 (median 1.7 years post-cancer-diagnosis). Multivariable linear regression was performed on each HRQL domain, separately for all cancers combined, major cancer sites, and cancer-free peers. RESULTS: Higher optimism and social support were significantly associated with better HRQL across various domains in women with and without a cancer diagnosis (p < 0.05). Mean HRQL scores across all domains for all cancer sites were significantly higher among optimistic versus not optimistic women with cancer (p < 0.05). Adjusting for sociodemographic and other health conditions, lower optimism was associated with reduced scores across all domains, with greater reductions in mental health (adjusted mean difference (AMD) = -11.54, p < 0.01) followed by general health (AMD = -11.08, p < 0.01). Social support was less consistently related to HRQL scores, and following adjustment was only significantly associated with social functioning (AMD = -7.22, p < 0.01) and mental health (AMD = -6.34, p < 0.01). CONCLUSIONS: Our findings highlight a strong connection between optimism, social support, and HRQL among cancer survivors. Providing psychosocial support and addressing behavioral and socioeconomic factors and other health conditions associated with optimism and social support may improve HRQL.

Biocomputational characterisation of MBO_200107 protein of Mycobacterium tuberculosis variant caprae: a molecular docking and simulation study.

The principal objective of this study was to delineate the potentiality of the MBO_200107 protein from the Mycobacterium tuberculosis variant caprae in cancer research. It is a cytoplasmic protein, comprised of a 354-long amino acid chain, alkaline, had a molecular weight of 39089.37 Da, an isoelectric point of 9.62 and a grand average of hydropathicity of -0.345. One of the functional domains was predicted as Gammaglutamylcyclotransferase (GGCT). Among tertiary structures, the Modeller and Phyre2 model satisfied all the quality parameters, though they are truncated; contrarily, the I-TASSER model is full length and contains the sequence for the GGCT domain, though it did not meet all the quality parameters. It also has significant sequence similarities (47.5% by EMBOSS Water and 72.4% by EMBOSS Matcher) with a human GGCT, and the conserved sequences are confined to the GGCT domain of the MBO_200107. According to molecular docking analyses, the protein has a binding affinity of -4.8 kcal/mol by Autodock Vina and -56.465 kcal/mol by HPEPDOCK to the human glutathione (GSH), an essential metabolite for GGCT metabolism. The Molecular dynamic simulation of the docked complex showed the binding efficiency of the GSH to MBO_200107 with a minimal structural alteration. The in silico findings mentioned above revealed that the protein could be used as a supplementary tool in cancer research, such as designing vaccines or drugs where the role of GGCT has been implicated. Further, we recommend fully characterising the protein and conducting essential in vitro and in vivo experiments to determine its detailed usefulness.Communicated by Ramaswamy H. Sarma.

The Impact of Education and Lifestyle Factors on Disability-Free Life Expectancy From Mid-Life to Older Age: A Multi-Cohort Study.

Objectives: Low education and unhealthy lifestyle factors such as obesity, smoking, and no exercise are modifiable risk factors for disability and premature mortality. We aimed to estimate the individual and joint impact of these factors on disability-free life expectancy (DFLE) and total life expectancy (TLE). Methods: Data (n = 22,304) were from two birth cohorts (1921-26 and 1946-51) of the Australian Longitudinal Study on Women's Health and linked National Death Index between 1996 and 2016. Discrete-time multi-state Markov models were used to assess the impact on DFLE and TLE. Results: Compared to the most favourable combination of education and lifestyle factors, the least favourable combination (low education, obesity, current/past smoker, and no exercise) was associated with a loss of 5.0 years TLE, 95% confidence interval (95%CI): 3.2-6.8 and 6.4 years DFLE (95%CI: 4.8-7.8) at age 70 in the 1921-26 cohort. Corresponding losses in the 1946-51 cohort almost doubled (TLE: 11.0 years and DFLE: 13.0 years). Conclusion: Individual or co-ocurrance of lifestyle risk factors were associated with a significant loss of DFLE, with a greater loss in low-educated women and those in the 1946-51 cohort.

Network-Based Genetic Profiling Reveals Cellular Pathway Differences Between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma.

Molecular mechanisms underlying the pathogenesis and progression of malignant thyroid cancers, such as follicular thyroid carcinomas (FTCs), and how these differ from benign thyroid lesions, are poorly understood. In this study, we employed network-based integrative analyses of FTC and benign follicular thyroid adenoma (FTA) lesion transcriptomes to identify key genes and pathways that differ between them. We first analysed a microarray gene expression dataset (Gene Expression Omnibus GSE82208, n = 52) obtained from FTC and FTA tissues to identify differentially expressed genes (DEGs). Pathway analyses of these DEGs were then performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) resources to identify potentially important pathways, and protein-protein interactions (PPIs) were examined to identify pathway hub genes. Our data analysis identified 598 DEGs, 133 genes with higher and 465 genes with lower expression in FTCs. We identified four significant pathways (one carbon pool by folate, p53 signalling, progesterone-mediated oocyte maturation signalling, and cell cycle pathways) connected to DEGs with high FTC expression; eight pathways were connected to DEGs with lower relative FTC expression. Ten GO groups were significantly connected with FTC-high expression DEGs and 80 with low-FTC expression DEGs. PPI analysis then identified 12 potential hub genes based on degree and betweenness centrality; namely, TOP2A, JUN, EGFR, CDK1, FOS, CDKN3, EZH2, TYMS, PBK, CDH1, UBE2C, and CCNB2. Moreover, transcription factors (TFs) were identified that may underlie gene expression differences observed between FTC and FTA, including FOXC1, GATA2, YY1, FOXL1, E2F1, NFIC, SRF, TFAP2A, HINFP, and CREB1. We also identified microRNA (miRNAs) that may also affect transcript levels of DEGs; these included hsa-mir-335-5p, -26b-5p, -124-3p, -16-5p, -192-5p, -1-3p, -17-5p, -92a-3p, -215-5p, and -20a-5p. Thus, our study identified DEGs, molecular pathways, TFs, and miRNAs that reflect molecular mechanisms that differ between FTC and benign FTA. Given the general similarities of these lesions and common tissue origin, some of these differences may reflect malignant progression potential, and include useful candidate biomarkers for FTC and identifying factors important for FTC pathogenesis.

Successful ageing from old to very old: a longitudinal study of 12,432 women from Australia.

OBJECTIVES: We examined the development of disease and disability in a large cohort of older women, the extent to which these conditions exempt them from being classified as successful agers and different trajectories of disease, disability and longevity across women's later life. METHODS: We used survey data from 12,432 participants of the 1921-26 birth cohort of the Australian Longitudinal Study of Women's Health from 1996 (age 70-75) to 2016 (age 90-95). Repeated measures latent class analysis (RMLCA) identified trajectories of the development of disease with or without disability and according to longevity. Bivariate analyses and multivariable multinomial logistic regression models were used to examine the association between participants' baseline characteristics and membership of the latent classes. RESULTS: Over one-third of women could be considered to be successful agers when in their early 70s, few women could still be classified in this category throughout their later life or by the end of the study when they were in their 90s (~1%). RMLCA identified six trajectory groups including managed agers long survivors (9.0%) with disease but little disability, usual agers long survivors (14.9%) with disease and disability, usual agers (26.6%) and early mortality (25.7%). A small group of women having no major disease or disability well into their 80s were identified as successful agers (5.5%). A final group, missing surveys (18.3%), had a high rate of non-death attrition. Groups were differentiated by a number of social and health factors including marital status, education, smoking, body mass index, exercise and social support. CONCLUSIONS: The study shows different trajectories of disease and disability in a cohort of ageing women, over time and through to very old ages. While some women continue into very old age with no disease or disability, many more women live long with disease but little disability, remaining independent beyond their capacity to be classified as successful agers.