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New Directions in the Study and Treatment of Metastatic Cancer.

Traditional cancer therapy has relied on a strictly cytotoxic approach that views non-metastatic and metastatic tumor cells as identical in terms of molecular biology and sensitivity to therapeutic intervention. Mounting evidence suggests that, in fact, non-metastatic and metastatic tumor cells differ in key characteristics that could explain the capacity of the metastatic cells to not only escape the primary organ but also to survive while in the circulation and to colonize a distant organ. Here, we lay out a framework for a new multi-pronged therapeutic approach. This approach involves modif

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with e

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… The GBD study is organised by a geographical hierarchy of seven super-regions containing 21 regions, with 195 countries and territories nested within those regions. 12 GBD 2016 included new subnational assessments for Indonesia by province and for England by local government area. …

Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).

As a member of BET (bromodomain and extra-terminal) protein family, BRD4 (bromodomain‑containing protein 4) is a chromatin‑associated protein that interacts with acetylated histones and actively recruits regulatory proteins, leading to the modulation of gene expression and chromatin remodeling. The cellular and epigenetic functions of BRD4 implicate normal development, fibrosis and inflammation. BRD4 has been suggested as a potential therapeutic target as it is often overexpressed and plays a critical role in regulating gene expression programs that drive tumor cell proliferation, survival, mi

Designing optimal allocations for cancer screening using queuing network models.

Cancer is one of the leading causes of death, but mortality can be reduced by detecting tumors earlier so that treatment is initiated at a less aggressive stage. The tradeoff between costs associated with screening and its benefit makes the decision of whom to screen and when a challenge. To enable comparisons across screening strategies for any cancer type, we demonstrate a mathematical modeling platform based on the theory of queuing networks designed for quantifying the benefits of screening strategies. Our methodology can be used to design optimal screening protocols and to estimate their

Machine Learning: A New Prospect in Multi-Omics Data Analysis of Cancer.

Cancer is defined as a large group of diseases that is associated with abnormal cell growth, uncontrollable cell division, and may tend to impinge on other tissues of the body by different mechanisms through metastasis. What makes cancer so important is that the cancer incidence rate is growing worldwide which can have major health, economic, and even social impacts on both patients and the governments. Thereby, the early cancer prognosis, diagnosis, and treatment can play a crucial role at the front line of combating cancer. The onset and progression of cancer can occur under the influence of

Routes of administration, reasons for use, and approved indications of medical cannabis in oncology: a scoping review.

INTRODUCTION: Some patients diagnosed with cancer use medical cannabis to self-manage undesirable symptoms, including nausea and pain. To improve patient safety and oncological care quality, the routes of administration for use of medical cannabis, patients' reasons, and prescribed indications must be better understood. METHODS: Based on the Joanna Briggs Institute guidelines, a scoping review was conducted to map the current evidence regarding the use of medical cannabis in oncological settings based on the experiences of patients diagnosed with cancer and their healthcare providers. A searc

Osteoporosis and the Potential of Cell-Based Therapeutic Strategies.

Osteoporosis, the most common chronic metabolic bone disease, is characterized by low bone mass and increased bone fragility. Nowadays more than 200 million individuals are suffering from osteoporosis and still the number of affected people is dramatically increasing due to an aging population and longer life, representing a major public health problem. Current osteoporosis treatments are mainly designed to decrease bone resorption, presenting serious adverse effects that limit their safety for long-term use. Numerous studies with mesenchymal stem cells (MSCs) have helped to increase the knowl

Tumour-associated macrophages: versatile players in the tumour microenvironment.

Tumour-Associated Macrophages (TAMs) are one of the pivotal components of the tumour microenvironment. Their roles in the cancer immunity are complicated, both pro-tumour and anti-cancer activities are reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis and tumour regression. Interestingly, TAMs are highly dynamic and versatile in solid tumours. They show anti-cancer or pro-tumour activities, and interplay between the tumour microenvironment and cancer stem cells and under specific conditions. In addition to the c

Phosphodiesterase type 5 and cancers: progress and challenges.

Cancers are an extraordinarily heterogeneous collection of diseases with distinct genetic profiles and biological features that directly influence response patterns to various treatment strategies as well as clinical outcomes. Nevertheless, our growing understanding of cancer cell biology and tumor progression is gradually leading towards rational, tailored medical treatments designed to destroy cancer cells by exploiting the unique cellular pathways that distinguish them from normal healthy counterparts. Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a

Эпштейн-Барр Вирус: больше чем просто инфекция.

Хотя вирус Эпштейн-Барр обычно ассоциируется с доброкачественным инфекционным мононуклеозом, он в настоящее время признается в качестве одного из основных движителей сложных иммунопатологических расстройств. Замыкаясь между литическими репликациями и стратегическими программами запоздалости, EBV перепрограммирует биологию B-клеток, чтобы избежать иммунного наблюдения и нарушить гомеостаз. Центральным элементом этого патогенеза является вирусный протеин EBNA1, который приводит к автоматическому иммунитету с помощью молекулярной имитации с принимающими антигенами, включая GlialCAM в множестве ск

Global, regional, and national burden of 34 cancer groups across 204 countries and territories, 1990-2021, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021.

IntroductionDetailed, comprehensive, and timely reporting on cancer incidence, mortality, and associated burdens is essential for understanding the evolving trends of this complex disease. This study aims to evaluate the burdens of 34 types of cancer across 204 countries and territories from 1990 to 2021, incorporating the latest epidemiological data to provide a framework for policy discussions, resource allocation, and research prioritization.MethodsUsing data from the Global Burden of Disease (GBD) 2021 study, we analyzed 34 cancer types across 204 countries from 1990 to 2021, stratifying b

SETD2 and EZH2: Two epigenetic drivers of prostate cancer.

Prostate cancer is a prevalent malignancy among men, characterized by complex mechanisms underlying metastasis and treatment resistance. Epigenetic modifications play a crucial role in regulating prostate cancer progression, particularly involving histone methyltransferases such as SET-domain containing 2 (SETD2) and Enhancer of Zeste homolog 2 (EZH2). SETD2 contributes to chromatin stability by catalyzing the trimethylation of histone H3 lysine 36 (H3K36me3), and its downregulation is strongly correlated with increased invasiveness and epithelial-mesenchymal transition in prostate cancer. Con

Catchment area and cancer population health research through a novel population-based statewide database: a scoping review.

BackgroundPopulation-based linked datasets are vital to generate catchment area and population health research. The novel Cancer Information and Population Health Resource (CIPHR) links statewide cancer registry data, public and private insurance claims, and provider- and area-level data, representing more than 80% of North Carolina's large, diverse population of individuals diagnosed with cancer. This scoping review of articles that used CIPHR data characterizes the breadth of research generated and identifies further opportunities for population-based health research.MethodsArticles publishe

Treatment decision making (TDM): a qualitative study exploring the perspectives of patients with chronic haematological cancers.

OBJECTIVES: Haematological malignancies are the fifth most common cancer in the UK, with chronic subtypes comprising around a third of all new diagnoses. These complex diseases have some similarities with other cancers, but often require different management. Surgical resection is not possible, and while some are curable with intensive chemotherapy, most indolent subtypes are managed with non-aggressive intermittent or continuous treatment, often over many years. Little is known about the views of patients with chronic haematological cancers regarding treatment decision making (TDM), a deficit

Histone modifications across cancers: mechanisms, therapy and clinical translation.

Cancer continues to be a major cause of death across the globe, and epigenetic dysregulation, including histone modifications, has been recognized as a major hallmark of cancer development, heterogeneity, and drug resistance. This review seeks to offer an overview of histone modifications in cancer, including the more studied histone modifications such as acetylation and methylation, as well as the less explored histone modifications such as phosphorylation, ubiquitination, and glycosylation. It also examines the role of histone modifications in the dysregulation of the three categories of enz

Current landscape of gene-editing technology in biomedicine: Applications, advantages, challenges, and perspectives.

The expanding genome editing toolbox has revolutionized life science research ranging from the bench to the bedside. These "molecular scissors" have offered us unprecedented abilities to manipulate nucleic acid sequences precisely in living cells from diverse species. Continued advances in genome editing exponentially broaden our knowledge of human genetics, epigenetics, molecular biology, and pathology. Currently, gene editing-mediated therapies have led to impressive responses in patients with hematological diseases, including sickle cell disease and thalassemia. With the discovery of more e

Chimeric Antigen Receptor T Cells as Living Therapeutics Targeting Senescence and Age-Related Diseases.

The aging of the global population exacerbates the burden of age-related diseases; however, therapies that can intervene in fundamental aging processes are lacking. Senescent cells drive chronic inflammation and multitissue dysfunction through the secretion of proinflammatory and profibrotic senescence-associated secretory phenotype cells, making them emerging therapeutic targets. Although first-generation senolytic drugs have entered clinical trials, they face limitations such as insufficient targeting specificity and transient efficacy. The success of chimeric antigen receptor T cell (CAR T

Poly(ethylene glycol)-Prodrug Conjugates: Concept, Design, and Applications.

Poly(ethylene glycol) (PEG) is the most widely used polymer in delivering anticancer drugs clinically. PEGylation (i.e., the covalent attachment of PEG) of peptides proteins, drugs, and bioactives is known to enhance the aqueous solubility of hydrophobic drugs, prolong circulation time, minimize nonspecific uptake, and achieve specific tumor targetability through the enhanced permeability and retention effect. Numerous PEG-based therapeutics have been developed, and several have received market approval. A vast amount of clinical experience has been gained which has helped to design PEG prodru

Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat.

Epigenetic regulation of gene transcription by small molecule inhibitors of histone deacetylases (HDAC) is a novel cancer therapy. Vorinostat (Zolinza()) is the first FDA approved HDAC-inhibitor for treatment of patients with cutaneous T cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in Phase I development. In two Phase II trials, vorinostat was safe and effective at an oral dose of 400 mg/day with an overall response r

Androgen Receptor-CaMKK2 Axis in Prostate Cancer and Bone Microenvironment.

The skeletal system is of paramount importance in advanced stage prostate cancer (PCa) as it is the preferred site of metastasis. Complex mechanisms are employed sequentially by PCa cells to home to and colonize the bone. Bone-resident PCa cells then recruit osteoblasts (OBs), osteoclasts (OCs), and macrophages within the niche into entities that promote cancer cell growth and survival. Since PCa is heavily reliant on androgens for growth and survival, androgen-deprivation therapy (ADT) is the standard of care for advanced disease. Although it significantly improves survival rates, ADT detrime