Результаты поиска

Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma.

Selinexor, an oral Selective Inhibitor of Nuclear Export, targets Exportin 1 (XPO1, also termed CRM1). Non-clinical studies support combining selinexor with proteasome inhibitors (PIs) and corticosteroids to overcome resistance in relapsed/refractory multiple myeloma (RRMM). We conducted a phase I dose-escalation trial of twice-weekly selinexor in combination with carfilzomib and dexamethasone (SKd) to determine maximum tolerated dose in patients with RRMM (N = 21), with an expansion cohort to assess activity in carfilzomib-refractory disease and identify a recommended phase II dose (RP2D). Du

Совпадение в полном тексте источника
… . & Borden , K.L. ( 2012 ) The oncogene eIF4E reprograms the nuclear pore complex to promote mRNA export and oncogenic transformation . …

Eltanexor Effectively Reduces Viability of Glioblastoma and Glioblastoma Stem-Like Cells at Nano-Molar Concentrations and Sensitizes to Radiotherapy and Temozolomide.

Current standard adjuvant therapy of glioblastoma multiforme (GBM) using temozolomide (TMZ) frequently fails due to therapy resistance. Thus, novel therapeutic approaches are highly demanded. We tested the therapeutic efficacy of the second-generation XPO1 inhibitor Eltanexor using assays for cell viability and apoptosis in GBM cell lines and GBM stem-like cells. For most GBM-derived cells, IC50 concentrations for Eltanexor were below 100 nM. In correlation with reduced cell viability, apoptosis rates were significantly increased. GBM stem-like cells presented a combinatorial effect of Eltanex

"Smart" drug delivery: A window to future of translational medicine.

Chemotherapy is the mainstay of cancer treatment today. Chemotherapeutic drugs are non-selective and can harm both cancer and healthy cells, causing a variety of adverse effects such as lack of specificity, cytotoxicity, short half-life, poor solubility, multidrug resistance, and acquiring cancer stem-like characteristics. There is a paradigm shift in drug delivery systems (DDS) with the advent of smarter ways of targeted cancer treatment. Smart Drug Delivery Systems (SDDSs) are stimuli responsive and can be modified in chemical structure in response to light, pH, redox, magnetic fields, and e

Triple‑negative breast cancer cell‑derived piR‑31115 promotes the proliferation and migration of endothelial cells via METTL3‑mediated m6A modification of YAP1.

Triple‑negative breast cancer (TNBC), a highly malignant breast cancer subtype with a pronounced metastatic propensity, forms the focus of the present investigation. MDA‑MB‑231, a prevalently utilized TNBC cell line in cancer research, was employed. In accordance with the tumour angiogenesis theory, cancer cells are capable of instigating angiogenesis and the formation of a novel vascular system within the tumour microenvironment, which subsequently sustains malignant proliferation and metastasis. Consequently, impeding the growth of tumour blood vessels holds substantial significance in suppr

Последствия злоупотребления наркотиками для путей ферроптоза: потенциальные терапевтические цели для расстройств, связанных с потреблением психоактивных веществ.

Серьезными проблемами в области здравоохранения во всем мире, особенно в развитых странах, по-прежнему являются расстройства, связанные с потреблением психоактивных веществ. Для ОСВ характерна устойчивая нейроинфламмация и синаптическая дисфункция мозга. Несмотря на десятилетия интенсивного расследования, детальные механизмы, лежащие в основе ВСГ, по-прежнему остаются иллюзорными. Ферроптоз — это высокорегулируемый процесс смерти клеток, на который сильно влияют метаболизм железа, пероксидация липидов, производство реактивных видов кислорода (РОС) и антиоксидантные системы. Он был связан с мно

Sinusoidal Obstruction Syndrome (SOS) in Multiple Myeloma with Renal Failure.

SOS is a rare complication of stem cell transplantation and has significant morbidity and mortality. We present three cases of SOS and highlight underlying risk factors for its development, such as impaired clearance of alkylating agents (especially melphalan) in patients with renal failure and prolonged infection. Although, melphalan and cyclophosphamide cause SOS less commonly than alkylating agents such as busulfan, physicians must use caution when administering these drugs to patients with underlying comorbidities such as renal failure that may increase the likelihood of development of SOS

Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors.

The field of immuno-oncology has revolutionized cancer patient care and improved survival and quality of life for patients. Much of the focus in the field has been on exploiting the power of the adaptive immune response through therapeutic targeting of T cells. While these approaches have markedly advanced the field, some challenges remain, and the clinical benefit of T cell therapies does not extend to all patients or tumor indications. Alternative strategies, such as engaging the innate immune system, have become an intense area of focus in the field. In particular, the engagement of natural

Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells.

The Wnt/β-catenin signaling pathway plays a major role in cell survival and proliferation, as well as in angiogenesis, migration, invasion, metastasis, and stem cell renewal in various cancer types. However, the modulation (either up- or downregulation) of this pathway can inhibit cell proliferation and apoptosis both through β-catenin-dependent and independent mechanisms, and by crosstalk with other signaling pathways in a wide range of malignant tumors. Existing studies have reported conflicting results, indicating that the Wnt signaling can have both oncogenic and tumor-suppressing roles, d

KIF11 promotes rheumatoid arthritis pathogenesis by activating M1 macrophage polarization and promoting inflammatory cytokine secretion.

BACKGROUND AND OBJECTIVE: KIF11, a mitotic kinesin, has been implicated in oncogenesis, but its specific role and mechanism in RA pathogenesis remain largely unexplored. We aim to explore functional role and molecular mechanism of KIF11 to promote RA progression. METHODS: Bioinformatics analysis was first performed on public RA datasets (GSE55457, GSE55235, GSE2053, GSE12021, and GSE1919) to identify KIF11-associated DEGs and their enriched pathways using GO/KEGG and GSEA analysis. Lentivirus-mediated shRNA was employed to knock down KIF11 expression in MH7A cells and M1-polarized macrophages

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

Amyloid Proteins and Peripheral Neuropathy.

Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired amyloid polyneuropathies, as well as some common diseases, including type 2 diabetes mellitus and several chronic inflammatory diseases. Intriguingly, these diseases share a histopathological feature-deposits of amyloid-forming proteins in tissues. Amyloid-forming proteins may cause tissue dysregulation and damage, including damage to nerves, and may be a common cause of neuropathy in these, and potentially other, diseases. He

Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).

Cisplatin resistance remains a primary obstacle in oncology, leading to therapeutic failure and disease recurrence. While resistance mechanisms are multifactorial, metabolic reprogramming has emerged as a critical adaptive strategy for cancer cells to evade cisplatin-induced cytotoxicity. This review synthesizes current evidence on how altered metabolism drives cisplatin resistance, with a particular emphasis on the pivotal role of pyruvate dehydrogenase kinases (PDKs). PDKs act as metabolic gatekeepers by inhibiting the pyruvate dehydrogenase complex (PDHC), diverting glucose flux away from m

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

Effect of pilose antler polypeptide on the mechanism of bone homeostasis in osteoporosis.

Osteoporosis stands out as a prevalent metabolic disorder, bearing significant repercussions on human well-being and overall quality of life. It remains an urgent concern within the global public health framework due to its widespread occurrence. Osteoporosis arises from an abnormal metabolism in osteoblasts and osteoclasts, resulting in a disruption of the delicate equilibrium between bone formation and bone resorption. Within this context, deer antler peptides emerge as natural active compounds, wielding a pivotal role in governing the differentiation, proliferation, and mineralization of os

Терапевтический потенциал кетогенного диета в лечении прогрессивного множественного склероза

До недавнего времени множественный склероз рассматривался как полностью подстрекательское заболевание без признания значительного нейродегенеративного компонента, ответственного за прогрессирование заболеваний и инвалидность. Этому аспекту мешают наблюдения о диссоциации между воспалением и нейродегенерацией, когда нейродегенеративный компонент может играть более важную роль в прогрессии заболеваний. В этом обзоре мы изучаем взаимосвязь между митохондриальной дисфункцией и нейродегенерацией при множественном склерозе. Мы анализируем доказательства того, что кетогенная диета может улучшить функ

Evaluating venetoclax and its potential in treatment-naïve acute myeloid leukemia.

Venetoclax (ABT-199), a BH3-mimetic and selective BCL-2 inhibitor, was recently approved by the US Food and Drug Administration (FDA) for the treatment of acute myeloid leukemia (AML) in adult patients aged 75 years or older, or otherwise unable to tolerate intensive induction chemotherapy, in combination with either hypomethylating agents or low-dose cytarabine. In this review article, we discuss venetoclax's mechanism of action, in relation to both the BCL-2 protein family in general and BH3-mimetic activity in particular. We then outline the pharmacological advances that preceded and facili

Уточнение роли селинксора в множестве миеломы: стратегическое использование в изменяющемся ландшафте обработки.

Площадь лечения множественной миеломы (ММ) революционизировалась в прошлом two десятилетиями, приводящими к беспрецедентным глубоким и долговременным ответным мерам, продолжительному выживанию и улучшению качества жизни. Тем не менее ММ по-прежнему является неизлечимым заболеванием, и многие пациенты, особенно больные цитогенетическими заболеваниями высокого риска, почечными расстройствами или ранней резистентностью к лекарственным препаратам, по-прежнему сталкиваются с плохими последствиями. Селинксор, первый в классе, в устной форме биодоступный селективный ингибитор экспорта 1 (XPO1) продем

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… Selinexor MoA and synergy with other anti-MM drugs Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), plays a critical role in the nuclear export of a wide range of cargo proteins, including tumor suppressor proteins (TSPs) like retinoblastoma and p53, through the nuclear pore …

Androgen Receptor-CaMKK2 Axis in Prostate Cancer and Bone Microenvironment.

The skeletal system is of paramount importance in advanced stage prostate cancer (PCa) as it is the preferred site of metastasis. Complex mechanisms are employed sequentially by PCa cells to home to and colonize the bone. Bone-resident PCa cells then recruit osteoblasts (OBs), osteoclasts (OCs), and macrophages within the niche into entities that promote cancer cell growth and survival. Since PCa is heavily reliant on androgens for growth and survival, androgen-deprivation therapy (ADT) is the standard of care for advanced disease. Although it significantly improves survival rates, ADT detrime

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… In a recent follow-up study, these authors confirmed the higher nuclear expression of CaMKK2 in CRPC C4-2 cells, and showed that this occurs due to the association of CaMKK2 with nuclear pore complexes through its direct interaction with nucleoporin 62 (NUP62) ( 107 ). …

Molecular factors associated with lung cancer in people living with HIV.

Lung cancer is the most common Non-AIDS-Defining Cancer (NADC) and a leading cause of cancer-related death in People Living With HIV (PLWH). Despite antiretroviral therapy, PLWH are at higher risk of developing cancer compared to the general population. This increased susceptibility reflects a combination of immunosuppression, chronic inflammation, smoking, and direct oncogenic effects of HIV proteins. Tat, gp120, and Nef modulate cell cycle control, apoptosis, epithelial-mesenchymal transition, angiogenesis, and immune evasion. Persistent HIV reservoirs in lung tissue (mainly effector memory

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… The viral DNA is subsequently imported through nuclear pores and integrated into the host genome. …

Эстрадиол содействует ремонту Myelin в Spinal Cord of Women Mice в CXCR4 Chemokine Receptor-Nependent.

В центральной нервной системе для взрослых (ЦНС) регенерация миелина происходит главным образом за счет дифференциации клеток олигодендроцитов потомства на зрелые олигодендроциты. У мужчин снижение уровня тестостерона ускоряет развитие множественных склерозов (МС), в то время как у женщин менопауза усугубляет инвалидность, связанную с НР. Ранее мы продемонстрировали, что функциональные яички и тестостерон необходимы для спонтанной ремимиилации фокус-лизолицитина (LPC), вызванной демиелином повреждения позвоночника мужских мышей. Ремонт миелина на основе тестостерона зависел от введения хемокин