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Mechanisms and Clinical Applications of Genome Instability in Multiple Myeloma.

Ongoing genomic instability represents a hallmark of multiple myeloma (MM) cells, which manifests largely as whole chromosome- or translocation-based aneuploidy. Importantly, although it supports tumorigenesis, progression and, response to treatment in MM patients, it remains one of the least understood components of malignant transformation in terms of molecular basis. Therefore these aspects make the comprehension of genomic instability a pioneering strategy for novel therapeutic and clinical speculations to use in the management of MM patients. Here we will review mechanisms mediating genom

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… NHEJ works primarily during G0-G1 phases of cell cycle. It promotes DNA broken ends bridging without using a specific template resulting therefore in a less accurate repair of DSB. …

Сердечные биомаркеры для стратификации риска в недавно диагностированном миеломе высокого риска в пробе GMG-CONCEPT.

Сердечно-сосудистые неблагоприятные явления (CVAE) являются клиническими побочными эффектами во время лечения протеаозным ингибитором карфилзомиба. Мы изучили прогнозируемую ценность сердечных биомаркеров для начала CVAE у пациентов с недавно поставленным диагнозом множественной миэломы повышенного риска, обработанных изатуксимабом, карфиломибом, линалидомидом и дексаметазоном в исследовании GMG-CONCEPT (GMG-CONCEPT).NCT03104842). Пациенты, включенные в это перспективное, многоцентровое корреляционное исследование, имеют право на получение пробы сыворотки до начала лечения и на ≥ 1 позднее был

Transcriptome Meta-Analysis of Triple-Negative Breast Cancer Response to Neoadjuvant Chemotherapy.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with varying responses to neoadjuvant chemotherapy (NAC). The identification of biomarkers to predict NAC response and inform personalized treatment strategies is essential. In this study, we conducted large-scale gene expression meta-analyses to identify genes associated with NAC response and survival outcomes. The results showed that immune, cell cycle/mitotic, and RNA splicing-related pathways were significantly associated with favorable clinical outcomes. Furthermore, we integrated and divided the gene association results from

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… It encodes a protein that forms a complex with cyclin-dependent kinase 4 (CDK4) or CDK6, promoting the progression of cells through the G1 phase of the cell cycle. Aberrant expression of CCND1 has been found in a variety of human cancers, including breast cancer [ 50 , 51 , 52 ]. …

Advances of DNA Damage Repair-Related Drugs and Combination With Immunotherapy in Tumor Treatment.

Cancer therapy has been an important and popular area in cancer research. With medical technology developing, the appearance of various targeted drugs and immunotherapy offer more choices to cancer treatment. With the increase in drug use, people have found more and more cases in which tumors are resistant to DNA damage repair (DDR)-based drugs. Recently, the concept of combination therapy has been brought up in cancer research. It takes advantages of combining two or more therapies with different mechanisms, aiming to benefit from the synergistic effects and finally rescue patients irresponsi

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… DNA Damage During the G0/G1 Phase Triggers RNA-Templated, Cockayne Syndrome B-Dependent Homologous Recombination. PNAS (2015) 112(27):E3495–504. doi: 10.1073/pnas.1507105112 9. Keung MYT, Wu Y, Vadgama JV. …

Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients.

Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount

Phase 1b study of the anti-CD38 antibody mezagitamab in patients with relapsed/refractory multiple myeloma.

This phase 1b trial aimed to determine the safety, tolerability, and preliminary efficacy of mezagitamab, a subcutaneously administered anti-CD38 monoclonal antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Eligible patients had received ≥3 prior lines of treatment, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and a steroid, or ≥2 prior lines in which 1 included a PI + IMiD, and were refractory or intolerant to ≥1 IMiD and ≥1 PI. Fifty patients were enrolled: 44 received mezagitamab monotherapy (dose-escalating cohorts at 45-1200 mg) and 6 recei

Оптимизация Белантамаба Мафодотина при рецидиве или резистентной множественной миеломе: влияние изменений дозы на нежелательные реакции и гематологическую реакцию в реальном мире ретроспективном исследовании.

Фон: Белантамаб мафодотин (belamaf) — это антитело-лекарственный конъюгат, мишенью которого является BCMA, используемый при тройном классе резистентной множественной миеломы. Несмотря на свою эффективность, кератопатия остается значимой дозоограничивающей токсичностью. После от withdrawal из американского рынка в 2022 году его использование в Австрии ограничено клиническими испытаниями или компассивным использованием. Методы: В этом реальном мире, ретроспективном исследовании мы проанализировали 36 пациентов с рецидивом/резистентной множественной миеломой, не имеющих предыдущего опыта с BCMA,

Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.

Zinc metabolism at the cellular level is critical for many biological processes in the body. A key observation is the disruption of cellular homeostasis, often coinciding with disease progression. As an essential factor in maintaining cellular equilibrium, cellular zinc has been increasingly spotlighted in the context of disease development. Extensive research suggests zinc's involvement in promoting malignancy and invasion in cancer cells, despite its low tissue concentration. This has led to a growing body of literature investigating zinc's cellular metabolism, particularly the functions of

Кишечная флора связана с риском возникновения хронических неинфекционных заболеваний.

КИСЛОТА: Кишечная флора (IF) связана с риском неинфекционных заболеваний, особенно различных видов рака, инсульта и болезни Альцгеймера. Однако на различных этапах роста, развития и старения все еще существует много неопределенностей в отношении этих ассоциаций. Поэтому необходимы дальнейшие углубленные исследования. AIM: Изучение связей человека с риском заболевания на различных этапах роста, развития и старения в целях получения более точных и убедительных выводов.МЕТОДЫ: Коорт, кросс-секции, контроль за конкретными случаями и исследования по случайной менделии, опубликованные в базах данных

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… On the contrary, Lactobacillus lactis can cause cell cycle arrest at the G0/G1 phase, thereby playing an anti-tumor role by inducing apoptosis[ 24 ]. For breast cancer, the IF plays an important role in regulating systemic estrogen[ 77 ]. …

Unlocking the potential of tumor-targeting peptides in precision oncology.

Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy, which is often plagued by poor selectivity, off-target effects, and drug resistance. Among the various targeting agents in development, peptides stand out for their unique advantages, including minimal immunogenicity, high tissue penetration, and ease of modification. Their small size, specificity, and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively. Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery, improvi

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… Unique compounds like Apratoxin A from Lyngbya majuscula halt the cell cycle in G1 phase [ 97 ], while Beauvericin from Fusarium induces caspase-mediated apoptosis [ 98 ]. Collectively, these peptides highlight the therapeutic promise of microbial bioactive compounds in oncology. … and HT-29 | Breast, liver, gastric and colon | – | Spirulina platensis | [ 95 ] CPAP | – | HepG2 | Liver cancer | Apoptosis together with necrotic demise | Chlorella pyrenoidosa | [ 96 ] Apratoxin A | – | HeLa and HT29 | Cervical carcinoma and colon adenocarcinoma | Causing a cell cycle stop in the G1 …

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention.

The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death pr

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… HDACs influence cell cycle and cellular proliferation, and HDAC inhibition induces cell cycle arrest at the G1 phase by reducing the expression of cyclins and cyclin-dependent kinases (CDK) or inducing the expression of CDK inhibitors [ 23 , 24 ]; HDACs inhibition also regulates cancer cell apoptosis … This small-molecule HDACi induces the expression of the cyclin-dependent kinase inhibitor 1 (p21/WAF1) expression, which suppresses cell-cycle progression at the G1 phase and induces cellular differentiation [ 73 ]. …

An overview of the potential anticancer properties of cardamonin.

Cancer is one of the leading causes of mortality, contributing to 9.6 million deaths globally in 2018 alone. Although several cancer treatments exist, they are often associated with severe side effects and high toxicities, leaving room for significant advancements to be made in the field. In recent years, several phytochemicals from plants and natural bioresources have been extracted and tested against various human malignancies using both in vitro and in vivo preclinical model systems. Cardamonin, a chalcone extracted from the Alpinia species, is an example of a natural therapeutic agent that

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… Furthermore, cardamonin was reported to increase of p21, and decrease CDK1, cyclin B1, and CDC25c to block the AGS cells in the G0/G1 phase of the cell cycle [ 49 ]. …

Potential Therapeutic Targets of Resveratrol, a Plant Polyphenol, and Its Role in the Therapy of Various Types of Cancer.

Cancer is among the most prominent causes of mortality worldwide. Different cancer therapy modes employed, including chemotherapy and radiotherapy, have been reported to be significant in cancer management, but the side effects associated with these treatment strategies are still a health problem. Therefore, alternative anticancer drugs based on medicinal plants or their active compounds have been generating attention because of their less serious side effects. Medicinal plants are an excellent source of phytochemicals that have been recognized to have health-prompting effects through modulati

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… Cell cycle analysis showed that that resveratrol may induce cell cycle arrest in the G0/G1 phase via downregulating the expression levels of cyclin D1, cyclin-dependent kinase (CDK)4 and CDK6, and upregulating the expression levels of the p21 and p27 and CDK inhibitors [ 65 ]. …

Contemporary patient-tailored treatment strategies against high risk and relapsed or refractory multiple myeloma.

Recurrence of disease due to chemotherapy drug resistance remains a major obstacle to a more successful survival outcome of multiple myeloma (MM). Overcoming drug resistance and salvaging patients with relapsed and/or refractory (R/R) MM is an urgent and unmet medical need. Several new personalized treatment strategies have been developed against molecular targets to overcome this drug resistance. There are several targeted therapeutics with anti-MM activity in clinical pipeline, including inhibitors of anti-apoptotic proteins, monoclonal antibodies, antibody-drug conjugates, bispecific antibo

Radiotherapy based management during Covid-19 pandemic - A systematic review of presented consensus and guidelines.

Treatment management of cancer patients in the radiation oncology departments during the current COVID-19 pandemic is challenging. A systematic review of published consensus/guidelines on the role of radiotherapy prioritization, suggested treatment protocols, and set up management was undertaken based on the PRISMA protocol and through PubMed/PMC, Scopus, Google Scholar, Web of Science databases until 01/20/2021. One hundred and sixty-eight publications or regional consensus were included. Summary of recommendations contained: (1) using hypo-fractionated (Hypo-F) regimens for therapeutic/palli

Financial Toxicity in Patients With Breast Cancer Treated at Private Medicine Institutions in Brazil.

Financial toxicity (FT) refers to the negative impact of the financial burden of cancer diagnosis and treatment on patients' well-being. With rising global costs of oncologic therapies, diagnostics, and supportive care, FT has become a key concern in cancer care, influencing adherence, quality of life, and outcomes. Breast cancer, given its high prevalence and socioeconomic implications, is notably associated with FT. Beyond direct medical expenses, patients often face income loss and out-of-pocket costs for supportive care, which can significantly affect their therapeutic trajectory. Addressi

Identification of a novel cuproptosis-related gene signature for multiple myeloma diagnosis.

BackgroundMultiple myeloma (MM) ranks second among the most prevalent hematological malignancies. Recent studies have unearthed the promise of cuproptosis as a novel therapeutic intervention for cancer. However, no research has unveiled the particular roles of cuproptosis-related genes (CRGs) in the prediction of MM diagnosis.MethodsMicroarray data and clinical characteristics of MM patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed gene analysis, least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature e

Evolving Therapeutic Strategies for the Classic Philadelphia-Negative Myeloproliferative Neoplasms.

Despite the emergence of JAK inhibitors, there is a need for disease-modifying treatments for Philadelphia-negative myeloproliferative neoplasms (MPNs). JAK inhibitors ameliorate symptoms and address splenomegaly, but because of the heterogeneous contributors to the disease process, JAK inhibitor monotherapy incompletely addresses the burden of disease. The ever-growing understanding of MPN pathogenesis has provided the rationale for testing novel and targeted therapeutic agents, as monotherapies or in combination, in preclinical and clinical settings. A number of intriguing options have emerg

Epithelial-Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications.

Radiation therapy is a fundamental component of cancer treatment, benefiting 50%-70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial-mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N-cadherin, and downregulating epithelial markers, such as E-cadherin. EMT under radiation involves principal signaling pathways, including TGF-β, Wnt/β-catenin, Notch, and ERK, which regulate EMT through transcription factors such as

Precision medicine: The use of tailored therapy in primary immunodeficiencies.

Primary immunodeficiencies (PID) are rare, complex diseases that can be characterised by a spectrum of phenotypes, from increased susceptibility to infections to autoimmunity, allergy, auto-inflammatory diseases and predisposition to malignancy. With the introduction of genetic testing in these patients and wider use of next-Generation sequencing techniques, a higher number of pathogenic genetic variants and conditions have been identified, allowing the development of new, targeted treatments in PID. The concept of precision medicine, that aims to tailor the medical interventions to each patie