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Perspectives on the Risk-Stratified Treatment of Multiple Myeloma.

The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article d

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… Translocations involving chromosome 14 and expression of cyclin D genes have been used to segment multiple myeloma into 7 biologically distinct segments [the Translocation-Cyclin D (TC) classification; ref. 10 ]. … The varied distribution and impact of RAS codon and other key DNA alterations across the translocation cyclin D subgroups in multiple myeloma . Oncotarget 2017 ; 8 : 27854 – 67 . 28427158 10.18632/oncotarget.15718 PMC5438613 104. …

Dietary Polyphenols and Their Biological Significance

Dietary polyphenols represent a wide variety of compounds that occur in fruits, vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They are mostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins and phenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis, anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascular protection, improvement of the endothelial function, as well as inhibition of angiogenesis and cell proliferation activity. Most of these biological actions have bee

Xanthohumol: Mechanistic Actions and Emerging Evidence as a Multi-Target Natural Nutraceutical.

BACKGROUND: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. OBJECTIVE: We aimed to structure XN's mechanistic hierarchy with emerging translational relevance across disease areas. METHODS: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. RESULTS: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-on

Targeting KRAS in NSCLC: Old Failures and New Options for "Non-G12c" Patients.

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene mutations are among the most common driver alterations in non-small cell lung cancer (NSCLC). Despite their high frequency, valid treatment options are still lacking, mainly due to an intrinsic complexity of both the protein structure and the downstream pathway. The increasing knowledge about different mutation subtypes and co-mutations has paved the way to several promising therapeutic strategies. Despite the best results so far having been obtained in patients harbouring KRAS exon 2 p.G12C mutation, even the treatment landscape of non-p.

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs hav

Механистические и переводческие данные о натуральных продуктах растительного происхождения в предклинических исследованиях по миеломе: текущие данные.

Множественная миелома (ММ) — гематологическая порча, характеризующаяся клональным распространением аномальных плазменных клеток с ярко выраженной гетерогенностью и терапевтической рефлексорностью. Несмотря на внедрение протеазонных ингибиторов (ИП), иммуноводных препаратов (ИМИД), моноклонных антител (mAbs) и химерика антигенного рецептора Т-клеток (CAR-T), рецидивы и резистентность к лекарствам по-прежнему остаются серьезными проблемами, требующими неотложного решения. В последние годы природные продукты растительного происхождения привлекают все большее внимание в связи с их многоцелевым син

A Perspective on Withania somnifera Modulating Antitumor Immunity in Targeting Prostate Cancer.

Medicinal plants serve as a lead source of bioactive compounds and have been an integral part of day-to-day life in treating various disease conditions since ancient times. Withaferin A (WFA), a bioactive ingredient of Withania somnifera, has been used for health and medicinal purposes for its adaptogenic, anti-inflammatory, and anticancer properties long before the published literature came into existence. Nearly 25% of pharmaceutical drugs are derived from medicinal plants, classified as dietary supplements. The bioactive compounds in these supplements may serve as chemotherapeutic substance

Autoimmune Gastritis With Progression of Leukemic Non-Nodal Mantle Cell Lymphoma.

The pathogenesis of autoimmune gastritis (AIG) remains unclear. In addition, it is difficult to follow the process of AIG onset endoscopically. Leukemic non-nodal mantle cell lymphoma (MCL) was newly added as a subtype of MCL in the fourth revised edition of the World Health Organization (WHO) classification (2017). Here, we report a case of AIG associated with the progression of leukemic non-nodal MCL. A 74-year-old woman who had been followed up in a nearby hospital for chronic B-cell lymphoproliferative disorder with no treatment for six years presented with fever and fatigue in the previou

t(14;16)-positive multiple myeloma shows negativity for CD56 expression and unfavorable outcome even in the era of novel drugs.

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Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature.

BackgroundPlasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.Case summaryOur aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the lit

NF-κB in Thyroid Cancer: An Update.

The dysregulated NF-κB basal activity is a common feature of human thyroid carcinomas, especially in poorly differentiated or undifferentiated forms that, even if rare, are often resistant to standard therapies, and, therefore, are uncurable. Despite the molecular mechanisms leading to NF-κB activation in thyroid cancer being only partially understood, during the last few years, it has become clear that NF-κB contributes in different ways to the oncogenic potential of thyroid neoplastic cells. Indeed, it enhances their proliferation and viability, promotes their migration to and colonization o

Relationship between Medication-Related Osteonecrosis of the Jaw and CDK4/6 Inhibitors in Breast Cancer.

OBJECTIVE: We aimed to evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. METHODS: This was a multicentre, retrospective, observational study. All patients with breast cancer treated with denosumab (January 2011-December 2022) were included. The relationship between CDK4/6 inhibitors and MRONJ was analysed. RESULTS: A total of 243 patients were included, ninety-five (44.2%) of whom used a CDK4/6 inhibitor. There were 21 patients with MRONJ. In patients tre

Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.

Chemotherapy (CT) is one of the flagship options for the treatment of cancers worldwide. It involves the use of cytotoxic anticancer agents to kill or inhibit the proliferation of cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact cancer patient's quality of life and treatment outcomes. While the side effect toxicity is consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment and other aberrant signalling leading to apoptosis and necroptosis, recent studies show that f

KSHV and cancer: understanding the oncogenic machinery for next-generation diagnostic tools and therapies.

Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), is an oncogenic virus responsible for Kaposi's sarcoma (KS) and lymphoproliferative disorders like primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). This review explores KSHV's oncogenic mechanisms, focusing on its ability to manipulate host cell signaling, evade immune detection, and promote tumorigenesis through latent and lytic viral proteins. Key oncoproteins, such as LANA, vCyc, vFLIP, and vGPCR, activate cancer hallmarks, as sustained proliferation, immune evasion, angiogenesis, and re

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… As well as LANA, functional viral cyclin (vCyc- ORF72) belongs to the latency cluster and presents functional and structural similarity to its human homolog cyclin D (Li et al. 1997 ). vCyc binds and activates cyclin-dependent kinase 4/6 (Cdk’s 4/6) maintaining the cell cycle of the infected cell and …

Alternative Cancer Therapeutics: Unpatentable Compounds and Their Potential in Oncology.

Cancer remains a leading cause of death globally. Cancer patients often seek alternative therapies in addition to, or instead of, conventional treatments like chemotherapy, radiation, and surgery. The progress in medical advancements and early detection provides more treatment options; however, the development of cancer drugs requires a significant amount of time, demands substantial investments, and results in an overall low percent of regulatory approval. The complex relationship between patent protection and pharmaceutical innovation complicates cancer drug development and contributes to hi

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted t

Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives.

The classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which include polycythaemia vera, essential thrombocythaemia and primary myelofibrosis, originate from a stem cell-derived clonal myeloproliferation that manifests itself with variable haematopoietic cell lineage involvement; they are characterized by a high degree of similarities and the chance to transform each to the other and to evolve into acute leukaemia. Their molecular pathogenesis has been associated with recurrent acquired mutations in janus kinase 2 (JAK2) and myeloproliferative leukemia virus oncogene

Муриновая корреляция саркомы Эпштейна-Барра и саркомы Капози (MHV-68) представляет собой ценную модель для оценки чувствительности к антивирусным препаратам и взаимодействия в комбинаторных наркотиках.

Человеческие герпесвирусы представляют собой основные человеческие патогены. Особый интерес представляют члены подсемейства < < Герпесвирина > > , поскольку они вызывают хронические заболевания, такие, как рак, изменяя клеточные процессы и вводя клетки отдыха в непрерывно расширяющуюся фазу. Кроме того, в центре внимания постоянно находятся аутоиммунные заболевания, такие, как множественный склероз. Прототипический вирус человека - герпесвирус - вирус Эпштейна - Барра (ЭБВ) оказался трудно проанализировать в целях развития противовирусной терапии из-за проблем, связанных с распрост

Изучение механизма Shengmai San для лечения аденокарциномы легких на основе биоинформатики и моделирования молекулярной динамики.

Изучение механизма Shengmai San (SMS) в лечении аденокарциномы легких (LUAD) на основе комплексной стратегии, сочетающей «сетевую фармакологию, биоинформатику, стыковку молекулярной стыковки и моделирование молекулярной динамики», в целях разработки точной стратегии комбинированной терапии и выявления потенциальных биоактивных соединений. Дифференцированные гены в LUAD были выявлены в базе данных Gene Express Omnibus с использованием R (первоначально разработанные в Bell Laboratories и в настоящее время управляемые Lucent Technologies). Из энциклопедии традиционной китайской медицины были извл

Immune System and DNA Repair Defects in Ovarian Cancer: Implications for Locoregional Approaches.

In the last few years, substantial progress has been made in the treatment of ovarian cancer, with increased knowledge about the biology of the disease. Ovarian cancer is a neoplasm strongly linked to defects in DNA repair mechanisms, where deficiency in the homologous recombination (HR) system results in a better response of ovarian cancers to therapy, whether platinum-based chemotherapy, anthracyclines, or poly (ADP-ribose) polymerase (PARP) inhibitors. More recently, it has been demonstrated that different ovarian cancer histotypes may have different immunogenicity. Interestingly, defects i