Результаты поиска

Characterization of Belantamab Mafodotin-Induced Corneal Changes in Patients With Multiple Myeloma.

IMPORTANCE: Ocular surface events are a class effect of microtubule-inhibitor payload-containing antibody-drug conjugates (ADCs); the mechanism underlying these events has not been fully elucidated. OBJECTIVE: To characterize corneal epithelial changes in patients with relapsed or refractory multiple myeloma (RRMM) treated with belantamab mafodotin, a maleimidocaproyl monomethyl auristatin-F (MMAF)-containing ADC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3b case series study was conducted in the US from March 26, 2020, to November 21, 2022, among adults with RRMM. Data were

Isatuximab, bortezomib, lenalidomide и dexamethason for multieloma: динамика негатива MRD в исследовании IMROZ.

Квадруплетная терапия с Isa-VRd (изатуксимаб, велкад [бортезомиб], релимид [леналидомид] и дексаметасон), за которой последовала Иса-Рд в ходе случайного этапа 3 исследования IMROZ, дала значительную возможность выжить без прогрессирования пациентам, имеющим право на трансплантацию с недавно диагностированным множественным миэломой (NDMM). В ходе первичного анализа большее число пациентов, прошедших лечение Isa-VRd/Isa-Rd, достигли минимальной остаточной негативности (MRD) и полной реакции (MRD-отрицательной реакции) в любой момент времени, чем пациенты, получающие VRd, за которыми следует Rd.

Outcome of transforaminal epidural steroid injection for lumbar radiculopathy: initial three-year experience at Upendra Devkota Memorial-National Institute of Neurological and Allied Sciences, Nepal.

INTRODUCTION: Additional risk minimisation measures (aRMMs) for medicinal products are necessary to address specific important safety issues which may not be practically achieved through routine risk management measures alone. The implementation and determination of effectiveness for aRMMs can be a challenge as it involves multiple stakeholders. It is therefore important to have concise objectives to avoid undue burden on patients, healthcare professionals and the healthcare system. AIM: The aim of this study was to examine how aRMMs are implemented and how effectiveness is assessed in the Eu

The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in

Совпадение в полном тексте источника
… Among the numerous proteins regulated by NF-kB signalling, cyclin D1 plays a crucial role in cancer progression, since it is a key regulator of late G1 phase of cell cycle. …

The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogenesis. This has led to rigorous inves

The DAC system and associations with multiple myeloma.

Despite the clear progress achieved in recent years in the treatment of MM, most patients eventually relapse and therefore novel therapeutic options are still necessary for these patients. In this regard, several drugs that target specific mechanisms of the tumor cells are currently being explored in the preclinical and clinical setting. This manuscripts offers a review of the rationale and current status of the antimyeloma activity of one of the most relevant examples of these targeted drugs: deacetylase inhibitors (DACi). Several studies have demonstrated the prooncogenic activity of deacety

Совпадение в полном тексте источника
… Interestingly, a cell cycle arrest in G0/G1 phases has been demonstrated as a very common effect of most DACi analyzed. …

New Therapeutic Strategies for Adult Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy. Chromosomal and genetic analyses are important for the diagnosis and prognosis of AML. Some patients experience relapse or have refractory disease, despite conventional cytotoxic chemotherapies and allogeneic transplantation, and a variety of new agents and treatment strategies have emerged. After over 20 years during which no new drugs became available for the treatment of AML, the CD33-targeting antibody-drug conjugate gemtuzumab ozogamicin was developed. This is currently used in combination with standard

A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight.

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, "mushrooms," contains numerous compounds that exhibit interesting biological activities, including antitumor activity

Safety and efficacy of lenalidomide in relapsed or refractory multiple myeloma.

Lenalidomide is an oral immunomodulatory drug that has helped improve outcomes in multiple myeloma (MM) patients. Combination lenalidomide and dexamethasone (Len+Dex) has been shown to increase response rates and prolong survival compared with dexamethasone alone in patients with relapsed or refractory MM (RRMM). Clinical benefit may be greatest when Len+Dex is given at first relapse, and continued treatment appears to provide greater depth of response and improved survival outcomes. The most common adverse events associated with Len+Dex are cytopenias, which are predictable and manageable. Le

Elotuzumab monotherapy in patients with smouldering multiple myeloma: a phase 2 study.

Smouldering multiple myeloma (SMM) is associated with increased risk of progression to multiple myeloma within 2 years, with no approved treatments. Elotuzumab has been shown to promote natural killer (NK) cell stimulation and antibody-dependent cellular cytotoxicity (ADCC) in vitro. CD56dim (CD56dim /CD16+ /CD3- /CD45+ ) NK cells represent the primary subset responsible for elotuzumab-induced ADCC. In this phase II, non-randomized study (NCT01441973), patients with SMM received elotuzumab 20 mg/kg intravenously (cycle 1: days 1, 8; monthly thereafter) or 10 mg/kg (cycles 1, 2: weekly; every 2

Oxidative Stress and Cancer: Harnessing the Therapeutic Potential of Curcumin and Analogues Against Cancer.

Reactive oxygen species (ROS) are a class of bioactive molecules that are the by-products of many cellular functions. These molecules are present in normal cells at homeostatic levels but have been studied extensively in cancer due to their dysregulation resulting in pro- and anti-tumorigenic environments. Completely understanding the paradoxical nature of ROS in cancer is imperative to fully realize its modulation as cancer therapy. Studies into ROS have shown far-reaching effects in cancer, including how ROS levels regulate signaling, response to treatment, drug resistance, etc. Many drugs w

Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of O6-methylguanine DNA methyltransferase as a biomarker for response.

Recent advances in the treatment of neuroendocrine tumors (NET), including the combination regimen of capecitabine and temozolomide (CAPTEM), have mostly focused on grade 1 and 2 pancreatic neuroendocrine tumors (pNET). We undertook a retrospective review of 38 patients with advanced NET treated with CAPTEM, including patients with non-pancreatic tumors as well as grade 2 and 3 tumors. O6-methylguanine DNA methyltransferase (MGMT) expression was assessed as a predictive biomarker. We found that CAPTEM demonstrated activity in patients with all grades and in pNET and non-pNET. Median progressio

A Review of Recent Curcumin Analogues and Their Antioxidant, Anti-Inflammatory, and Anticancer Activities.

Curcumin, as the main active component of turmeric (Curcuma longa), has been demonstrated with various bioactivities. However, its potential therapeutic applications are hindered by challenges such as poor solubility and bioavailability, rapid metabolism, and pan-assay interference properties. Recent advancements have aimed to overcome these limitations by developing novel curcumin analogues and modifications. This brief review critically assesses recent studies on synthesising different curcumin analogues, including metal complexes, nano particulates, and other curcumin derivatives, focused o

Совпадение в полном тексте источника
… The four analogues, including curcumin (IC 50 = 4.19 μM), bisdemethoxycurcumin (IC 50 = 29.15 μM), demethoxycurcumin (IC 50 = 30.03 μM), and dimethoxy curcumin (IC 50 = 29.55 μM), were found to promote the sub-G1 phase, G2/M arrest, apoptosis, and ROS production in human glioma cells, with dimethoxy …

Transferrin-conjugated SNALPs encapsulating 2'-O-methylated miR-34a for the treatment of multiple myeloma.

Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed. Wild type or completely 2'-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs.

MTAP-Null Tumors: A Comprehensive Review on Synthetic Vulnerabilities and Therapeutic Strategies.

Homozygous deletion of the 9p21.3 genomic locus spanning the CDKN2A/B and MTAP genes is an event affecting 15% of cancers. While CDKN2A is a well-established tumor suppressor gene, the role of MTAP in tumorigenesis varies across cancer types. MTAP codes for methylthioadenosine phosphorylase, a key enzyme in the methionine salvage pathway, and its loss has been associated with several downstream synthetic vulnerabilities. Despite multiple efforts to exploit MTAP loss for targeted therapies, none of these efforts have yielded substantial results in clinical trials. In this review, we consolidate

Совпадение в полном тексте источника
… /GlaxoSmithKline | Retinoblastoma | Inhibited retinoblastoma cell proliferation and led to cell cycle arrest at the G1 phase | [ 94 ] MTA-cooperative PRMT5 inhibitors | MRTX1719 | Mirati Therapeutics | Solid tumors | Antitumor activity across a panel of xenograft models (lung carcinoma, colorectal, mesothelioma … EPZ015666 (GSK3235025) inhibited retinoblastoma cell proliferation and induced cell cycle arrest at the G1 phase [ 94 ]. These two drugs, however, have not been tested in clinical trials. …

Novel therapies emerging in oncology to target the TGF-β pathway.

The TGF-β signaling pathway governs key cellular processes under physiologic conditions and is deregulated in many pathologies, including cancer. TGF-β is a multifunctional cytokine that acts in a cell- and context-dependent manner as a tumor promoter or tumor suppressor. As a tumor promoter, the TGF-β pathway enhances cell proliferation, migratory invasion, metastatic spread within the tumor microenvironment and suppresses immunosurveillance. Collectively, the pleiotropic nature of TGF-β signaling contributes to drug resistance, tumor escape and undermines clinical response to therapy. Based

The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy.

BackgroundMyrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life.MethodThe current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)

Opportunities and Challenges of Small Molecule Induced Targeted Protein Degradation.

Proteolysis targeting chimeras (PROTAC) represents a new type of small molecule induced protein degradation technology that has emerged in recent years. PROTAC uses bifunctional small molecules to induce ubiquitination of target proteins and utilizes intracellular proteasomes for chemical knockdown. It complements the gene editing and RNA interference for protein knockdown. Compared with small molecule inhibitors, PROTAC has shown great advantages in overcoming tumor resistance, affecting the non-enzymatic function of target proteins, degrading undruggable targets, and providing new rapid and

Совпадение в полном тексте источника
… PROTAC Can Overcome Tumor Drug Resistance Caused by CDK4/6 Mutations Cyclin dependent kinase 4/6 (CDK4/6), an important part of the cyclin family, plays a regulatory role in the transition from the G1 phase to the S phase in the cell cycle ( Vermeulen et al., 2003 ). …

фазы 2 Судебный процесс над Фрексалимабом, антагонистом CD40L, среди подростков и взрослых с недавним-оффсетным типом 1 Диабет (ФАБУЛИНУС): Обоснование и проект исследований.

Введение 1 диабет (T1D) — хроническое аутоиммунное заболевание, характеризующееся постепенным уничтожением инсулиновых β-клеток. Сохранение оставшихся β-клеток на момент диагностики может улучшить долгосрочные результаты. Frexalib — это гуманная моноклональная антитела, специально предназначенная для CD40L, которая проходит оценку на предмет лечения различных иммунизированных заболеваний. фазы 2 - испытание для оценки эффективности и безопасности фрексалимаб для сохранения поджелудочной функции β-клетки у подростков и молодых взрослых (12-35 с недавно поставленным диагнозом " Этап "

Rosmarinic Acid and Related Dietary Supplements: Potential Applications in the Prevention and Treatment of Cancer.

Cancer constitutes a severe threat to human health and quality of life and is one of the most significant causes of morbidity and mortality worldwide. Natural dietary products have drawn substantial attention in cancer treatment and prevention due to their availability and absence of toxicity. Rosmarinic acid (RA) is known for its excellent antioxidant properties and is safe and effective in preventing and inhibiting tumors. This review summarizes recent publications on culture techniques, extraction processes, and anti-tumor applications of RA-enriched dietary supplements. We discuss techniqu

Совпадение в полном тексте источника
… Cell cycle-related inhibitors (cyclin-dependent kinases 4/6 inhibitors) arrest tumors in the G1 phase, thereby preventing proliferation; this mechanism has been applied in the treatment of several tumors [ 95 ]. … RA induced G0/G1-phase arrest in breast and pancreatic cancer [ 97 , 98 ]. G2/M arrest occurred in treating kidney cancer and oral cancer [ 99 , 100 ]. Cell cycle arrest represents an opportunity for cancer cells to enter apoptosis. …