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Human microbiomes in cancer development and therapy.

Colonies formed by bacteria, archaea, fungi, and viral groups and their genomes, metabolites, and expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis and disease progression were link to microbiomes. Different organ sources, their microbial species, and their metabolites are different; the mechanisms of carcinogenic or procancerous are also different. Here, we summarize how microbiomes contribute to carcinogenesis and disease progression in cancers of the skin, mouth, esophagus, lung, gastrointestinal, genital, blood, and lymph malignancy

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… Microbiomes, epigenomics, immune response, and splicing signatures interplay: potential use of combination of regulatory pathways as targets for malignant mesothelioma. Int J Mol Sci. 2022;23(16). 28. Woodhams DC, Bletz MC, Becker CG, et al. …

Osteoid cell-derived chemokines drive bone-metastatic prostate cancer.

One of the greatest challenges in improving prostate cancer (PCa) survival is in designing new therapies to effectively target bone metastases. PCa regulation of the bone environment has been well characterized; however, bone-targeted therapies have little impact on patient survival, demonstrating a need for understanding the complexities of the tumor-bone environment. Many factors contribute to creating a favorable microenvironment for prostate tumors in bone, including cell signaling proteins produced by osteoid cells. Specifically, there has been extensive evidence from both past and recent

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… Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma. Br J Cancer (2008) 98:496–501. doi: 10.1038/sj.bjc.6604180 146. Ha HK, Lee W, Park HJ, Lee SD, Lee JZ, Chung MK. …

Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance.

Atopic dermatitis (AD) is a chronic and relapsing cutaneous disorder characterized by compromised immune system, excessive inflammation, and skin barrier disruption. Post-translational modifications (PTMs) are covalent and enzymatic modifications of proteins after their translation, which have been reported to play roles in inflammatory and allergic diseases. However, less attention has been paid to the effect of PTMs on AD. This review summarized the knowledge of six major classes (including phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, o-glycosylation, and glycati

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… Epigenomics 9, 539–571. 10.2217/epi-2016-0162 Quah S., Subramanian G., Sampath P. (2021). Repurposing Belinostat for Alleviation of Atopic Dermatitis. Dermatol Ther. …

Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer.

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of t

Evolving therapy of adult acute lymphoblastic leukemia: state-of-the-art treatment and future directions.

Recent years have witnessed major advances that have improved outcome of adults with acute lymphoblastic leukemia (ALL). The emergence of the concept of measurable residual disease has fine-tuned our prognostic models and guided our treatment decisions. The treatment paradigms of ALL have been revolutionized with the advent of tyrosine kinase inhibitors targeting BCR-ABL1, monoclonal antibodies targeting CD20 (rituximab), antibody-drug conjugates targeting CD22 (inotuzumab ozogamicin), bispecific antibodies (blinatumomab), and CD19 chimeric antigen receptor T cell therapy (tisagenlecleucel). T

Immunotherapies for pediatric cancer: current landscape and future perspectives.

The advent of immunotherapy has revolutionized how we manage and treat cancer. While the majority of immunotherapy-related studies performed to date have focused on adult malignancies, a handful of these therapies have also recently found success within the pediatric space. In this review, we examine the immunotherapeutic agents that have achieved the approval of the US Food and Drug Administration for treating childhood cancers, highlighting their development, mechanisms of action, and the lessons learned from the seminal clinical trials that ultimately led to their approval. We also shine a

Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland-Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies-2018 Update.

IntroductionVitamin D deficiency is an important public health problem worldwide. Vitamin D deficiency confers a significant risk for both skeletal and non-skeletal disorders and a number of lifelong negative health outcomes. The objectives of this evidence-based guidelines document are to provide health care professionals in Poland, an updated recommendation for the prevention, diagnosis and treatment of vitamin D deficiency.MethodsA systematic literature search examining the prevention and treatment strategies for vitamin D deficiency was conducted. Updated recommendations were developed usi

mTOR Cross-Talk in Cancer and Potential for Combination Therapy.

The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understandi

Lost in Translation (LiT): IUPHAR Review 6.

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but t

Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.

Cytokines are essential components of the tumor microenvironment (TME) and play crucial roles in tumor initiation and progression. As key mediators of interactions between immune cells and tumor cells within the TME, many cytokines exhibit both protumor and antitumor properties. This complex duality, reminiscent of the balance philosophy pursued by "Onmyoji" in traditional Eastern philosophy, which involves observing and regulating opposing forces to achieve harmony, poses marked challenges in translating cytokine therapies from animal studies to clinical applications. More than 20 key cytokin

Metabolic reprogramming in cancer and senescence.

The rising trend in global cancer incidence has caused widespread concern, one of the main reasons being the aging of the global population. Statistical data show that cancer incidence and mortality rates show a clear upward trend with age. Although there is a commonality between dysregulated nutrient sensing, which is one of the main features of aging, and metabolic reprogramming of tumor cells, the specific regulatory relationship is not clear. This manuscript intends to comprehensively analyze the relationship between senescence and tumor metabolic reprogramming; as well as reveal the impac

Immunotherapies for Aging and Age-Related Diseases: Advances, Pitfalls, and Prospects.

Aging is characterized by a gradual decline in the functionality of all the organs and tissues, leading to various diseases. As the global population ages, the urgency to develop effective anti-aging strategies becomes increasingly critical due to the growing severity of associated health problems. Immunotherapy offers novel and promising approaches to combat aging by utilizing approaches including vaccines, antibodies, and cytokines to target specific aging-related molecules and pathways. In this review, we summarize the recent advancements of immunotherapies to eliminate senescence cells and

Spatiotemperal Dynamics of Osteoarthritis: Преобразование значений от стенда до Бедсайда.

Остеоартрит (OA) представляет собой многогранное дегенеративное совместное расстройство, вызванное различными факторами риска, такими, как возраст, механический стресс, воспаление и метаболическое воздействие. Эти элементы способствуют его разнообразным фенотипам и эндотипам, что подчеркивает имманентную сложность болезни. Участие нескольких тканей и их взаимодействие еще больше осложняет расследование ОА. Нынешние ограничения в области технологий пространственного фенотификации в сочетании со сложной сетью многофакторных взаимодействий препятствуют обнаружению надежных ранних диагностических

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

Systemic lupus erythematosus: pathogenesis and targeted therapy.

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress

Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.

Neuroendocrine neoplasms (NENs), which are characterized by neuroendocrine differentiation, can arise in various organs. NENs have been divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on morphological differentiation, each of which has a distinct etiology, molecular profile, and clinicopathological features. While the majority of NECs originate in the pulmonary organs, extrapulmonary NECs occur most predominantly in the gastro-entero-pancreatic (GEP) system. Although platinum-based chemotherapy is the main therapeut

DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.

Resistance to chemo- and radiotherapy is a common event among cancer patients and a reason why new cancer therapies and therapeutic strategies need to be in continuous investigation and development. DNA damage response (DDR) comprises several pathways that eliminate DNA damage to maintain genomic stability and integrity, but different types of cancers are associated with DDR machinery defects. Many improvements have been made in recent years, providing several drugs and therapeutic strategies for cancer patients, including those targeting the DDR pathways. Currently, poly (ADP-ribose) polymera

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

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… Recent advances in epigenomics have illuminated epigenetics in cancer stem cells (CSC) [ 225 ]. CSCs have been identified in a number of solid tumors, including breast cancer, brain tumors, lung cancer, colon cancer, and melanoma. …

The role and mechanisms of action of microRNAs in cancer drug resistance.

MicroRNAs (miRNAs) are small non-coding RNAs with a length of about 19-25 nt, which can regulate various target genes and are thus involved in the regulation of a variety of biological and pathological processes, including the formation and development of cancer. Drug resistance in cancer chemotherapy is one of the main obstacles to curing this malignant disease. Statistical data indicate that over 90% of the mortality of patients with cancer is related to drug resistance. Drug resistance of cancer chemotherapy can be caused by many mechanisms, such as decreased antitumor drug uptake, modified

Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.

BACKGROUND: Chemotherapy remains a foundation of cancer care but is limited by multidrug resistance, systemic toxicities, and suboptimal selectivity, prompting interest in adjunctive strategies that improve efficacy and tolerability without adding significant burden to patients or healthcare systems. AIMS/OBJECTIVES: This review highlights evidence on natural bioactive compounds, including polyphenols, alkaloids, terpenoids, and fungal metabolites, as adjuvants to standard chemotherapeutics, with objectives to: first, delineate mechanisms by which these agents enhance cytotoxic efficacy and o