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Инженерный антитела TACI × CD3 для перенаправления Т клеток на множественные миэломы.

Вышеупомянутые аббревиатуры, предназначенные для антигена созревания клеток В (BCMA), являющегося членом сверхсемейства суперрецептора некроза опухоли (TNFR), продемонстрировали замечательную клиническую эффективность в лечении рецидива/рефрактора множественной миеломы (MM). Вместе с тем одной из серьезных проблем является частое снижение регулирования или потеря выражения БКМА у пациентов, получающих иммунотерапию, ориентированную на БКМА, что существенно снижает терапевтическую эффективность и способствует прогрессированию и устойчивости к заболеваниям после первоначальной позитивной реакции

Repurposing anticancer drugs for the management of COVID-19.

Since its outbreak in the last December, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread worldwide at a pandemic proportion and thus is regarded as a global public health emergency. The existing therapeutic options for COVID-19 beyond the intensive supportive care are limited, with an undefined or modest efficacy reported so far. Drug repurposing represents an enthusiastic mechanism to use approved drugs outside the scope of their original indication and accelerate the discovery of new therapeutic options. With the emergence of COVID-19, drug repurposing has been la

Natural and semisynthetic candidate molecules for COVID-19 prophylaxis and treatment.

Coronaviruses (CoVs) represent a family of viruses that have numerous animal hosts, and they cause severe respiratory, as well as systemic and enteric infections, in humans. Currently, there are limited antiviral strategies for treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The lack of specific antiviral medicines and SARS-CoV-2 vaccines continues to aggravate the situation. Natural product-based antiviral drugs have been used in the two previous CoV outbreaks: Middle East respiratory syndrome coronavirus (MERS-CoV) and the first SARS-CoV. This re

DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.

Resistance to chemo- and radiotherapy is a common event among cancer patients and a reason why new cancer therapies and therapeutic strategies need to be in continuous investigation and development. DNA damage response (DDR) comprises several pathways that eliminate DNA damage to maintain genomic stability and integrity, but different types of cancers are associated with DDR machinery defects. Many improvements have been made in recent years, providing several drugs and therapeutic strategies for cancer patients, including those targeting the DDR pathways. Currently, poly (ADP-ribose) polymera

Role of autophagy in cholangiocarcinoma: Pathophysiology and implications for therapy.

Cholangiocarcinoma (CCA) is a malignant tumour of the biliary system that originates from the neoplastic transformation of cholangiocytes. CCA is characterized by late diagnosis and poor outcome, with surgery considered as the last option for management. Autophagy is a physiological lysosomal degradation process, essential for cellular homeostasis and ubiquitous in all eukaryotic cells. Several studies have reported a potential involvement of autophagy in cancer, but it remains unclear whether activation of this process represents a survival mechanism of cancer cells. In the present review, we

Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization.

BackgroundBrain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential stra

A Review of Repurposed Cancer Drugs in Clinical Trials for Potential Treatment of COVID-19.

The pandemic of the coronavirus disease 2019 (COVID-19) represents an unprecedented challenge to identify effective drugs for prevention and treatment. While the world's attention is focused on news of COVID-19 vaccine updates, clinical management still requires improvement. Due to the similarity of cancer-induced inflammation, immune dysfunction, and coagulopathy to COVID-19, anticancer drugs, such as Interferon, Pembrolizumab or Bicalutamide, are already being tested in clinical trials for repurposing, alone or in combination. Given the rapid pace of scientific discovery and clinical data ge

Наркотики, основанные на сходстве генных экспрессионных сигнатур, чтобы исследовать потенциальные признаки кексетина: тематическое исследование множественных склерозов.

Quercetin (QR) — природный флавонол, широко распространенный в королевстве растений с обширными фармакологическими последствиями. Чтобы найти потенциальные клинические показатели QR, 156 Дифференциально выраженные гены (DEG), регулируемые QR, были получены из базы данных Gene Express Omnibus, и новые потенциальные фармакологические эффекты и клинические показатели QR были перенаправлены путем интегрирования соединений с аналогичными генными сигнатурами возмущения и соответствующими сигнатурами болезни QR на основе карты связи и платформ Coexedia. Предлагаемые результаты QR оказывают главным об

The Role of Circulating MicroRNAs as Biomarkers and Therapeutic Targets in Venous Thromboembolism: A Systematic Review.

Introduction: Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cardiovascular disorder and a leading cause of vascular mortality. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate gene expression post-transcriptionally by binding to the target messenger RNAs (mRNAs), inducing mRNA degradation or translational repression. miRNA dysregulation likely contributes to VTE pathogenesis. This review comprehensively summarizes current evidence on miRNAs in VTE, offering a structured overview of the existing literature. Mate

Потенциальная роль TNFRSF12A в установлении связи между глиобластомой и болезнью Альцгеймера через общие пути подавления опухолей.

Гены, подавляющие опухоль, являются критическими регуляторами клеточного гомеостаза и широко изучаются в области онкологической биологии. Однако их роль в нейродегенеративных заболеваниях, особенно в болезни Альцгеймера, остается слабой. Недавние данные об обратной связи между раком и АД указывают на существование общих молекулярных механизмов. Мы провели комплексный анализ для выявления ТГС, которые могут участвовать как в AD, так и в глиобластоме (GBM), с использованием менделийской случайности, транскриптомного профилирования (булка и одноклеточная RNA-seq), вывода в отношении связи между к

Targeted Delivery Strategies for Multiple Myeloma and Their Adverse Drug Reactions.

Currently, multiple myeloma (MM) is a prevalent hematopoietic system malignancy, known for its insidious onset and unfavorable prognosis. Recently developed chemotherapy drugs for MM have exhibited promising therapeutic outcomes. Nevertheless, to overcome the shortcomings of traditional clinical drug treatment, such as off-target effects, multiple drug resistance, and systemic toxicity, targeted drug delivery systems are optimizing the conventional pharmaceuticals for precise delivery to designated sites at controlled rates, striving for maximal efficacy and safety, presenting a promising appr

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… HDP-101 , a fully human mAb directed at BCMA, is covalently bonded to an amanitin derivative via an indissoluble MC linker [ 32 ]. α-Amanitin, an octapeptide with a bicyclic structure, functions as an inhibitor of eukaryotic RNA polymerase II, capable of hindering cellular transcription and protein synthesis … The RNA polymerase II trigger loop functions in substrate selection and is directly targeted by alpha-amanitin. Mol. Cell. 2008;30:547–556. doi: 10.1016/j.molcel.2008.04.023. 34. …

Proceedings of International Conference on Cell Death in Cancer and Toxicology. February 20-22, 2018. Guest Editors: Kausar M. Ansari, CSIR-IITR, India and Dhyan Chandra, Roswell Park, USA.

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Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen

Совпадение в полном тексте источника
… polymerase II | Cleavable linker/site-specific | Heidelberg Pharma AG Munich, Germany 4 | MEDI2228 (anti-BCMA-pyrrolobenzodiazepine (PBD) conjugate) | IgG1 | PBD dimer is a DNA-targeting agent that binds to the minor groove and crosslinks DNA, leading to DNA damage | Protease-cleavable linker | MedImmune … HDP-101 Amanitin is an agent that is being investigated as a warhead for ADCs by Heidelberg Pharma, and functions through the potent and specific inhibition of RNA polymerase II [ 57 ] ( Table 1 ). …

From Selection to Use: Aptamers as Targeting Reagents in Hematology.

Aptamers are synthetic nucleic acid ligands that have been proposed as alternatives to antibodies for targeting molecules and cells. In hematology, most reviews have organized aptamer literature around diseases or technological platforms. This framing has obscured how unevenly different blood cell types have been covered. In this review, we present developed aptamers organized by blood cell lineages. Specifically, we examine aptamers for B cells, T cells, natural killer cells, and red blood cells. This organization revealed a strong concentration on a small set of canonical surface markers and

Человеческие эндогенные ретровирусы как новые терапевтические цели в нейродегенеративных расстройствах.

Человеческие эндогенные ретровирусы составляют приблизительно 8% генома человека и служат фрагментами древних антиретровирусных инфекций. Хотя они, как правило, удерживаются в замалчиваемом состоянии с помощью надежных эпигенетических механизмов, конкретные группы HERV, в частности HERV-W и HERV-K, могут депрессировать в конкретных патологических условиях, что способствует инициированию и продвижению нейро-воспалительных и нейродегенеративных процессов. Доклинические исследования и клинические испытания, такие, как исследования моноклонных антител, показывают, что прямая ориентация на эти элем

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

MicroRNAs in B-cells: from normal differentiation to treatment of malignancies.

MicroRNAs (miRNAs) are small non-coding RNAs that play important post-transcriptional regulatory roles in a wide range of biological processes. They are fundamental to the normal development of cells, and evidence suggests that the deregulation of specific miRNAs is involved in malignant transformation due to their function as oncogenes or tumor suppressors. We know that miRNAs are involved in the development of normal B-cells and that different B-cell subsets express specific miRNA profiles according to their degree of differentiation. B-cell-derived malignancies contain transcription signatu

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… In the canonical biogenesis pathway, intergenic miRNA genes are transcribed by RNA polymerase II into 5′-capped and 3′-polyadenylated molecules, the primary-miRNAs [ 17 ]. … Figure 1 Biogenesis of miRNAs The synthesis of miRNAs via the canonical pathway starts with transcription of miRNA genes by RNA polymerase II, which results in primary-miRNAs. …

Current perspectives on KMT2A fusion proteins and menin inhibition in paediatric acute myeloid leukaemia.

The therapeutic landscape of acute myeloid leukaemia (AML) has evolved beyond the classic '7 + 3'/DA regimen, through the approval and incorporation of targeted treatments in both front-line and relapsed/refractory settings. Indeed, the use of selective BCL-2 antagonists (e.g. venetoclax) and FLT3 inhibitors (e.g. midostaurin, gilteritinib) which target specific molecular characteristics of leukaemic cells, has enhanced outcomes and survival rates. Arguably one of the most exciting advancements has been the clinical development of menin inhibitors for the treatment of patients harbouring speci

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… In some reciprocal AFF1‐KMT2A fusion cases, the N‐terminal fused protein sequences are capable of binding both P‐TEFb and the largest subunit of RNA polymerase II to enhance transcriptional elongation. … MLLT3/AF9, MLLT10/AF10, ELL and MLLT1/ENL) are involved in transcriptional elongation, as they either bind directly or indirectly—via Super Elongation Complexes (SEC)—to RNA polymerase II [ 25 , 26 , 27 , 28 ]. …

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

Совпадение в полном тексте источника
… Fig. 1 dummy alt text Tat is a small regulatory protein that increases RNA polymerase II activity during viral genome transcription and downregulates MHC-I expression, contributing to immune evasion and viral persistence. …

Bone sialoprotein: a multifunctional regulator of bone remodelling and tumour progression.

Bone sialoprotein (BSP) is a major non-collagenous protein of the bone extracellular matrix and an important regulator of bone formation and resorption. BSP is produced by bone cells and chondrocytes and present in the bone matrix, cells, dentin and cartilage. However, its aberrant expression in primary tumour tissues and the sera of cancer patients with metastases implicates BSP in tumour biology and progression. The Arg-Gly-Asp (RGD) motif of BSP may be crucial not only for the attachment of metastasising cells to the bone surface but also for tumour growth, survival and activity. This revie