Результаты поиска

Boanmycin overcomes bortezomib resistance by inducing DNA damage and endoplasmic reticulum functional impairment in multiple myeloma.

BackgroundMultiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells and is currently incurable. Despite advancements in therapeutic strategies, resistance to proteasome inhibitors, particularly bortezomib (BTZ), poses a substantial challenge to disease management. This study aimed to explore the efficacy of boanmycin, a novel antitumor antibiotic, in overcoming resistance to BTZ in MM.MethodsBTZ-resistant cells were generated over a period of at least 6 months by gradually increasing the concentration of BTZ. The viability of MM cell lines

Совпадение в полном тексте источника
… The excessive production of monoclonal proteins leads to MM cells relying on the unfolded protein response (UPR) for survival, which increases their vulnerability to proteotoxicity [ 33 ]. …

Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry.

Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the compari

Metabolomics for hematologic malignancies: Advances and perspective.

With the use of advanced technology, metabolomics allows for a thorough examination of metabolites and other small molecules found in biological specimens, blood, and tissues. In recent years, metabolomics has been recognized that is closely related to the development of malignancies in the hematological system. Alterations in metabolomic pathways and networks are important in the pathogenesis of hematologic malignancies and can also provide a theoretical basis for early diagnosis, efficacy evaluation, accurate staging, and individualized targeted therapy. In this review, we summarize the prog

Совпадение в полном тексте источника
… PYCR1 inhibition reduces myeloma cell proliferation and survival by triggering unfolded protein response pathway in vitro and in vivo to increase the efficacy of bortezomib [ 44 ] (Fig. 4 ). …

Emerging Roles of Osteoclasts in the Modulation of Bone Microenvironment and Immune Suppression in Multiple Myeloma.

Multiple myeloma (MM) is one of the most common forms of hematologic malignancy resulting from cancerous proliferation of mature malignant plasma cells (MPCs). But despite the real improvement in therapeutics in the past years, it remains largely incurable. MM is the most frequent cancer to involve bone due to the stimulation of osteoclast (OCL) differentiation and activity. OCLs have a unique capacity to resorb bone. However, recent studies reveal that they are not restrained to this sole function. They participate in the control of angiogenesis, medullary niches, and immune responses, includ

Совпадение в полном тексте источника
… Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells . Blood ( 2006 ) 107 : 4907 – 16 . 10.1182/blood-2005-08-3531 16507771 PMC1895817 96 Mohty M Malard F Mohty B Savani B Moreau P Terpos E . …

Множественная миелома: сказка о дерегулированных факторах транскрипции.

Всеобъемлющее понимание молекулярных механизмов, лежащих в основе множественных миэломных (ММ) патогенеза, крайне важно для разработки терапевтических стратегий, позволяющих преодолеть гетерогенность заболеваний и рецидив лечения. В этом обзоре мы сосредоточимся на коэффициентах транскрипции (TF), ключевых регуляторах генного экспрессия, которые играют важнейшую роль в обычной гематопоизисе и биологии MM. Сначала мы обсудим физиологические функции ТФ в составе лимфоидной линии и конечной дифференциации В-клеток на плазменные клетки. Это позволяет получить представление о вкладе ключевых ЦГ, та

Descriptive Analysis of Adverse Events Reported for New Multiple Myeloma Medications Using FDA Adverse Event Reporting System (FAERS) Databases from 2015 to 2022.

BackgroundNew multiple myeloma (MM) medications have revolutionized the treatment landscape, but they are also associated with a range of adverse events (AEs). This study aims to provide a comprehensive overview of AEs reported for four new MM medications: daratumumab, ixazomib, elotuzumab, and panobinostat.MethodsThis study uses a descriptive retrospective approach to analyze the FDA Adverse Event Reporting System (FAERS) from 2015 to 2022. It includes variables like medication names, report details, patient demographics, adverse events, and reporter types. The initial dataset consists of ove

Совпадение в полном тексте источника
… Proteasome inhibitors disrupt the unfolded protein response in myeloma cells. Proc. Natl. Acad. Sci. USA. 2003;100:9946–9951. doi: 10.1073/pnas.1334037100. 58. van de Donk N.W.C.J., Richardson P.G., Malavasi F. CD38 antibodies in multiple myeloma: Back to the future. …

Diagnosis and treatment of multisystem amyloidosis associated with SGPL1 mutation: A case report and review of the literature.

RATIONALE: Amyloidosis is a rare, clinically heterogeneous disease, which makes its diagnosis difficult. The relationship between amyloidosis and gene mutations is insufficiently understood. We report a case of sphingosine-1-phosphate lyase 1 (SGPL1) mutation-related amyloidosis, and review the related literature. PATIENT CONCERNS: A 53-year-old man was admitted to our hospital with a 5-month history of renal dysfunction and abdominal distension, aggravated since 2 days. Five months ago, the patient was diagnosed with nephrotic syndrome, with liver dysfunction and abdominal distension. His sy

Healthy Effects of Plant Polyphenols: Molecular Mechanisms.

The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have

Распространяется жизнь, угрожая вирусом Нокардии отитидискавиарум у молодой женщины с недавно диагностированным системным волшебством эритематос, отчетом по делу и анализом литературы.

По сообщениям, инфекция, вызванная нокардией, наблюдается главным образом у иммунокомпромиссированных пациентов. Обычно он представляет собой легочную или распространенную болезнь с предрасположенностью к мозгу. Инфекции - это редкая этиология внутричерепной сосудистой аневризмы. В этой связи мы сообщаем о случае распространения Nocardia otitidiscaviarum (N. otitidiscaviarum) у молодой женщины, у которой недавно был диагностирован системный волчан (SLE), осложняемый развитием инфекционной внутричерепной аневризмы. Насколько нам известно, это четвертый случай внутричерепной аневризмы, связанной

Диабет мелитус в множестве миэломы и связанных с ним расстройства плазменных клеток: обзор риска, прогноза и результатов.

Существует четкая связь между типом 2 сахарный диабет и общий риск заболевания раком. Однако исследования, посвященные оценке типа 2 Риск ДМ и множественной миэломы (ММ) ограничен, и связь менее ясна. Понимание воздействия давнишнего типа 2 Важнейшее значение имеет DM о системах органов и симптоматологии у пациентов с последующим диагнозом MM, а также потенциальные перекликающиеся токсичные вещества, связанные с лечением MM. В настоящем обзоре резюмируется роль вида 2 ДМ о рисках и результатах ММ и изучает различные механизмы, лежащие в основе этих ассоциаций. Более глубокое понимание этой асс

Совпадение в полном тексте источника
… Metformin was shown to suppress the induction of critical unfolded protein response effector glucose-regulated protein 78 (GRP78) with consequent impairment of autophagosome formation and enhancement of apoptosis when combined with bortezomib treatment in MM cell lines and patient tumor cells in-vitro …

Mitochondrial Genetic and Epigenetic Regulations in Cancer: Therapeutic Potential.

Mitochondria are dynamic organelles managing crucial processes of cellular metabolism and bioenergetics. Enabling rapid cellular adaptation to altered endogenous and exogenous environments, mitochondria play an important role in many pathophysiological states, including cancer. Being under the control of mitochondrial and nuclear DNA (mtDNA and nDNA), mitochondria adjust their activity and biogenesis to cell demands. In cancer, numerous mutations in mtDNA have been detected, which do not inactivate mitochondrial functions but rather alter energy metabolism to support cancer cell growth. Increa

Ось MLKLOPTN регулирует вызванные герпесвирусом неврологические сиквелы.

КОЛИЧЕСТВО: герпес просторексовый вирус-1 (HSV-1) носит пожизненный характер и связан с неврологическими заболеваниями, такими, как множественный склероз (MS), однако основные механизмы в хосте остаются недостаточно понятными. МЕТОДЫ И РЕЗУЛЬТАТЫ: В настоящем исследовании изучается новая молекулярная динамика после заражения HSV-1, выявляется ключевая роль смешанного киназа-домена (MLKL). Помимо известной функции в некроптозе, было установлено, что MLKL контролирует перенос HSV-1 в ядро, жестко регулируемый Оптинёрином (Optineurin). Мы продемонстрировали существенное нормативное взаимодействие

Ocular Surface Side Effects of Novel Anticancer Drugs.

Surgery, anticancer drugs (chemotherapy, hormonal medicines, and targeted treatments), and/or radiation are common treatment strategies for neoplastic diseases. Anticancer drugs eliminate malignant cells through the inhibition of specific pathways that contribute to the formation and development of cancer. Given the ability of such pharmacological medications to combat cancerous cells, their role in the management of neoplastic diseases has become essential. However, these drugs may also lead to undesirable systemic and ocular adverse effects due to cyto/neuro-toxicity and inflammatory reactio

How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.

Cancer remains the leading cause of mortality worldwide. Radiotherapy (RT), a cornerstone of oncological treatment for over a century, has achieved great success in various cancers. However, radioresistance remains the primary factor leading to the failure of radiotherapy. Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure, either by loosening or tightening it. Here, we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal t

Всеобъемлющий анализ SOX7 дает новое представление о его роли опухоля и его целевых генах с терапевтическими последствиями в множестве миеломы.

Множественная миелома (ММ) — неизлечимая гематология. SOX7, расположенное в области 8p23.1 в MM, предлагается действовать в качестве ограничителя опухоли. Мы описали SOX7 с помощью генетического, эпигенетического и функционального анализа в линиях клеток MM. SOX7 часто замолчали из-за исключения и/или содействия гиперметилированию. Эктомическое выражение SOX7 в KMS-18 и MM.1S привело к постепенному снижению числа камер, передаваемых SOX7, и вызвало арест и/или апоптоз в клеточном цикле G1. Хотя повторное выражение SOX7 не повысило бортезомибную эффективность, лечение панхистоном деацетилазным

Совпадение в полном тексте источника
… While SOX7 mainly interferes with cell cycle progression by modulating transcriptional networks, bortezomib induces proteotoxic stress, endoplasmic reticulum stress, the activation of the unfolded protein response [ 38 ], and ultimately apoptosis. …

TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma : TGF-β in the microenvironment of multiple myeloma.

Although substantial quantities of potent therapies for multiple myeloma (MM) have been established, MM remains an incurable disease. In recent years, our understanding of the initiation, development, and metastasis of cancers has made a qualitative leap. Cancers attain the abilities to maintain proliferation signals, escape growth inhibitors, resist cell death, induce angiogenesis, and more importantly, escape anti-tumor immunity and reprogram metabolism, which are the hallmarks of cancers. Besides, different cancers have different tumor microenvironments (TME), thus, we pay more attention to

Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development.

Marine-derived bisindoles exhibit structural diversity and exert anti-cancer influence through multiple mechanisms. Comprehensive research has shown that the development success rate of drugs derived from marine natural products is four times higher than that of other natural derivatives. Currently, there are 20 marine-derived drugs used in clinical practice, with 11 of them demonstrating anti-tumor effects. This article provides a thorough review of recent advancements in anti-tumor exploration involving 167 natural marine bisindole products and their derivatives. Not only has enzastaurin ent

Development and Differentiation in Monobodies Based on the Fibronectin Type 3 Domain.

As a non-antibody scaffold, monobodies based on the fibronectin type III (FN3) domain overcome antibody size and complexity while maintaining analogous binding loops. However, antibodies and their derivatives remain the gold standard for the design of new therapeutics. In response, clinical-stage therapeutic proteins based on the FN3 domain are beginning to use native fibronectin function as a point of differentiation. The small and simple structure of monomeric monobodies confers increased tissue distribution and reduced half-life, whilst the absence of disulphide bonds improves stability in

Протеиновая пальмитиоляция в гематологическое облучение: механистические связи с липидным метаболическим перепрограммированием и резистентностью к терапии.

Протеиновая пальмитиолация стала центральным постпереходным механизмом, регулирующим локализацию белков, стабильность и трансдукцию сигналов. В гематологических галактиках эта динамическая модификация находится на пересечении липидного метаболического перепрограммирования, взаимодействия между опухолью и иммуном и терапевтического сопротивления. Здесь мы рассматриваем вопрос о том, как дисрегулированные пальмитоилпереносазы и депальмитолазы изменяют метаболические ферменты, липидные переносчики, липидно-дрофтовые белки, онкогенные сигнальные компоненты и молекулы иммунного регулирования, созда

Side Effects of Novel Anticancer Drugs on the Posterior Segment of the Eye: A Review of the Literature.

Currently, common treatment approaches for neoplastic diseases include surgery, radiation, and/or anticancer drugs (chemotherapy, hormone medications, and targeted therapies). In particular, anticancer medicines destroy cancerous cells by blocking certain pathways that aid in the disease's initiation and progression. These pharmaceutical drugs' capacity to inhibit malignant cells has made them indispensable in the treatment of neoplastic disorders. Nonetheless, considering their cyto- and neurotoxicity, as well as their inflammatory responses, these medications may also have unfavorable system