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Fanconi anemia pathway as a prospective target for cancer intervention.

Fanconi anemia (FA) is a recessive genetic disorder caused by biallelic mutations in at least one of 22 FA genes. Beyond its pathological presentation of bone marrow failure and congenital abnormalities, FA is associated with chromosomal abnormality and genomic instability, and thus represents a genetic vulnerability for cancer predisposition. The cancer relevance of the FA pathway is further established with the pervasive occurrence of FA gene alterations in somatic cancers and observations of FA pathway activation-associated chemotherapy resistance. In this article we describe the role of th

Chronic stress: a fourth etiology in tumorigenesis?

Chronic stress, driven by persistent psychological, environmental, or physiological factors, is a prolonged heightened state of stress response that disrupts homeostasis. When unmanaged, it will lead to sustained negative emotions such as depression, loneliness, anxiety, and emotional adversity. This persistent emotional distress not only exacerbates mental health disorders but also poses significant risks to physical health. Increasing evidence suggests a strong link between chronic stress, stress-related hormones, and the rising incidence of malignancies. As a result, chronic stress might be

CPUY201112, a novel synthetic small-molecule compound and inhibitor of heat shock protein Hsp90, induces p53-mediated apoptosis in MCF-7 cells.

Heat-shock protein 90 (Hsp90) is highly expressed in many tumor cells and is associated with the maintenance of malignant phenotypes. Targeting Hsp90 has had therapeutic success in both solid and hematological malignancies, which has inspired more studies to identify new Hsp90 inhibitors with improved clinical efficacy. Using a fragment-based approach and subsequent structural optimization guided by medicinal chemistry principles, we identified the novel compound CPUY201112 as a potent Hsp90 inhibitor. It binds to the ATP-binding pocket of Hsp90 with a kinetic dissociation (Kd) constant of 27

Pathologic and prognostic impacts of FGFR2 amplification in gastric cancer: a meta-analysis and systemic review.

Fibroblast growth factor receptor-2 (FGFR2) gene is amplified in up to 15% of patients with gastric cancer (GC). However, the prognostic significance of FGFR2 amplification has been controversial. This meta-analysis was conducted to evaluate the clinicopathological impacts of FGFR2 amplification in patients with GC. We performed a systematic computerized search of the electronic databases of PubMed, PMC, EMBASE, Web of Science, and Google Scholar and selected studies assessing the correlation of FGFR2 amplification with pathologic features and/or prognosis in gastric adenocarcinoma. From eight

Advances in antisense oligonucleotide treatment for cancer.

RNA therapeutics, including antisense oligonucleotides (ASOs), have emerged as a promising class of drugs, with several already approved for clinical use. To date, most approved ASO-based RNA therapies target non-malignant disorders such as neurodegenerative diseases, and only a single therapy in this class has been approved for cancer. Notably, nearly half of existing RNA therapeutics act by modulating RNA splicing. Given the growing evidence implicating aberrant RNA splicing in cancer pathogenesis, the development of ASO-based therapeutics for oncologic indications is expected to accelerate.

Clinical and Biological Characteristics of Four Patients with Aggressive Systemic Mastocytosis Treated with Midostaurin.

Systemic mastocytosis (SM) is a rare and heterogeneous disorder characterized by clonal proliferation and accumulation of neoplastic mast cells in one or more organs, most commonly the bone marrow, liver, spleen, and skin. Among its clinical variants, aggressive SM (ASM) presents organ damage and debilitating symptoms due to extensive mast cell infiltration. The management of ASM remains challenging, primarily because treatment must address both symptom control and disease progression. Background/Objectives: Recent therapeutic approaches have focused on tyrosine kinase inhibitors (TKIs) that t

Prevalence of Hypovitaminosis D in Adults Presenting With Generalized Aches: A Hospital-Based Observational Study.

INTRODUCTION AND AIM: Generalized aches mean widespread musculoskeletal pain. It has various etiologies, and among them, hypovitaminosis D is one of the common causes. This study aimed to determine the prevalence of hypovitaminosis D and to identify other causes of generalized aches in adults. METHODS: This retrospective, observational, descriptive study was conducted at Nepal Medical College and Teaching Hospital (NMCTH), Kathmandu, Nepal. Records of adults presenting to the rheumatology OPD with generalized aches from January 1, 2023, to December 31, 2024, were reviewed. Serum 25(OH)D and o

Paediatric Gliomas: BRAF and Histone H3 as Biomarkers, Therapy and Perspective of Liquid Biopsies.

Paediatric gliomas categorised as low- or high-grade vary markedly from their adult counterparts, and denoted as the second most prevalent childhood cancers after leukaemia. As compared to adult gliomas, the studies of diagnostic and prognostic biomarkers, as well as the development of therapy in paediatric gliomas, are still in their infancy. A body of evidence demonstrates that B-Raf Proto-Oncogene or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) and histone H3 mutations are valuable biomarkers for paediatric low-grade gliomas (pLGGs) and high-grade gliomas (pHGGs). Various diagnostic

Bidirectional Relationship Between Cancer and Heart Failure: Old and New Issues in Cardio-oncology.

The main focus of cardio-oncology has been the prevention and treatment of the cardiac toxicity of chemotherapy and radiotherapy. Furthermore, several targeted therapies have been associated with unexpected cardiotoxic side-effects. Recently, epidemiological studies reported a higher incidence of cancer in patients with heart failure (HF) compared with individuals without HF. On this basis, it has been proposed that HF might represent an oncogenic condition. This hypothesis is supported by preclinical studies demonstrating that hyperactivation of the sympathetic nervous system and renin-angiot

An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications.

Arsenic trioxide is a first-line treatment drug for acute promyelocytic leukemia, which is also effective for other kinds of leukemia. Its side effects, however, limit its clinical application, especially for patients with complex leukemia symptoms. Combination therapy can effectively alleviate these problems. This review summarizes the research progress on the combination of arsenic trioxide with anticancer drugs, vitamin and vitamin analogs, plant products, and other kinds of drugs in the treatment of leukemia. Additionally, the new progress in arsenic trioxide-induced cardiotoxicity was sum

Тематический анализ прогноза, диагностики и терапии циркулирующих биомаркеров миРНА в борцезомибно-стойких миеломах.

ЦЕЛЬ: Растущий спрос на точную медицину стимулировал молекулярные диагностические исследования, с тем чтобы подчеркнуть полезность микроРНК в качестве важных биомаркеров. В недавних исследованиях подчеркивается роль МИРНА как перспективных, диагностических и терапевтических биомаркеров в управлении и мониторинге нескольких пациентов, страдающих миеломой. Цель этого обзора заключается в том, чтобы представить последние сведения о потенциале распространения миРНА в качестве прогнозирующих, диагностических и терапевтических биомаркеров в нескольких миеломах, устойчивых к бортезомибу. МЕТОДЫ: С эт

Role of Exosomal Non-Coding RNAs in Bone-Related Diseases.

Bone-related diseases seriously affect the lives of patients and carry a heavy economic burden on society. Treatment methods cannot meet the diverse clinical needs of affected patients. Exosomes participate in the occurrence and development of many diseases through intercellular communication, including bone-related diseases. Studies have shown that exosomes can take-up and "package" non-coding RNAs and "deliver" them to recipient cells, thereby regulating the function of recipient cells. The exosomal non-coding RNAs secreted by osteoblasts, osteoclasts, chondrocytes, and other cells are invol

Potential Adverse Effects of Dexamethasone Therapy on COVID-19 Patients: Review and Recommendations.

In the context of the coronavirus disease 2019 (COVID-19) pandemic, the global healthcare community has raced to find effective therapeutic agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, dexamethasone is the first and an important therapeutic to significantly reduce the risk of death in COVID-19 patients with severe disease. Due to powerful anti-inflammatory and immunosuppressive effects, dexamethasone could attenuate SARS-CoV-2-induced uncontrolled cytokine storm, severe acute respiratory distress syndrome and lung injury. Nevertheless, dexamethasone tre

The management of type 2 inflammatory respiratory diseases: a Chinese expert consensus [2024].

BackgroundType 2 (T2) inflammatory respiratory diseases encompass a range of conditions characterized by inflammation affecting the airways and lung parenchyma, with their pathogenesis rooted in T2 inflammation. Biological treatments that mitigate T2 inflammation revolutionize the therapeutic landscape for these respiratory diseases. However, there are decision-making difficulties in terms of the target population, timing of initiation, and type selection for biological targeted therapy.MethodsSearch strategies were focused on relevant issues related to T2 inflammatory respiratory diseases fro

H3 histone methylation landscape in male urogenital cancers: from molecular mechanisms to epigenetic biomarkers and therapeutic targets.

During the last decades, male urogenital cancers (including prostate, renal, bladder and testicular cancers) have become one of the most frequently encountered malignancies affecting all ages. While their great variety has promoted the development of various diagnosis, treatment and monitoring strategies, some aspects such as the common involvement of epigenetic mechanisms are still not elucidated. Epigenetic processes have come into the spotlight in the past years as important players in the initiation and progression of tumors, leading to a plethora of studies highlighting their potential as

NEK2 регулирует функцию клеток B и остроту экспериментального аутоиммунного энцефаломиелита.

Никогда в гене митоза А (NIMA) 2 (NEK2) член семьи сереново-триониновая киназа принимает активное участие в регулировании клеточного цикла. Регулирование NEK2 связано с аномальным распространением клеток B, которое потенциально вызвано NEK2-mediated нарушение равновесия PKM1/PKM2. Чрезмерное выражение NEK2 в линии клеток B может облегчить процесс созревания клеток B. Тем не менее, точная роль НКЭК2 в модуляции иммунитета от аутоиммунных расстройств с помощью клеток В еще не полностью разъяснена. В этом исследовании мы продемонстрировали, что НКЭК2 была значительно усилена в отношении пациентов

The Roles of EDA2R in Ageing and Disease.

Ageing is a complex biological process driven, in part, by inflammaging. Recent research identifies the ectodysplasin A2 receptor (EDA2R) as a key regulator of inflammaging and a novel biomarker of ageing, with its expression increasing with age across diverse tissues in humans and animal models. Elevated EDA2R gene expression is associated with accelerated ageing, cellular senescence, frailty, obesity, acne, radiation response and increased levels of inflammatory, renal, cardiac and vascular biomarkers. Similarly, elevated EDA2R protein levels, a critical component of the proteomic ageing clo

The crosstalk between non-coding RNAs and oxidative stress in cancer progression.

As living standards elevate, cancers are appearing in growing numbers among younger individuals globally and these risks escalate with advancing years. One of the reasons is that instability in the cancer genome reduces the effectiveness of conventional drug treatments and chemotherapy, compared with more targeted therapies. Previous research has discovered non-coding RNAs' crucial role in shaping genetic networks involved in cancer cell growth and invasion through their influence on messenger RNA production or protein binding. Additionally, the interaction between non-coding RNAs and oxidativ

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… Protein kinase D2 is a crucial regulator of tumour cell-endothelial cell communication in gastrointestinal tumours. Gut. 2010;59(10):1316–1330. doi: 10.1136/gut.2009.206813. 64. Wille C., Köhler C., Armacki M., et al. … Protein kinase D2 induces invasion of pancreatic cancer cells by regulating matrix metalloproteinases. Mol Biol Cell. 2014;25(3):324–336. doi: 10.1091/mbc.E13-06-0334. 65. Yin D., Liu L., Shi Z., Zhang L., Yang Y. …

Repurposed Drugs in Gastric Cancer.

Gastric cancer (GC) is one of the major causes of death worldwide, ranking as the fifth most incident cancer in 2020 and the fourth leading cause of cancer mortality. The majority of GC patients are in an advanced stage at the time of diagnosis, presenting a poor prognosis and outcome. Current GC treatment approaches involve endoscopic detection, gastrectomy and chemotherapy or chemoradiotherapy in an adjuvant or neoadjuvant setting. Drug development approaches demand extreme effort to identify molecular mechanisms of action of new drug candidates. Drug repurposing is based on the research of

Advancement of NF-κB Signaling Pathway: A Novel Target in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers and is the third highest among cancer related deaths. Despite modest success with therapy such as gemcitabine, pancreatic cancer incidence remains virtually unchanged in the past 25 years. Among the several driver mutations for PDAC, Kras mutation contributes a central role for its development, progression and therapeutic resistance. In addition, inflammation is implicated in the development of most human cancer, including pancreatic cancer. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is recogniz