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T-cell-engaging antibodies for the treatment of solid tumors: challenges and opportunities.

Purpose of reviewT-cell-engaging antibodies or T-cell engagers (TCEs) can connect a patient's cytotoxic T cells with cancer cells, leading to potent redirected lysis. Until very recently, only one TCE was approved, the CD19/CD3-bispecific blinatumomab. Many new TCEs in late-stage clinical development target various hematopoietic lineage markers like CD20, BCMA, or CD123. Although very compelling single-agent activity of TCEs was observed with various blood-borne cancers, therapy of solid tumor indications has thus far been less successful.Recent findingsThe approval in 2022 of the gp100 peptid

Tumour Cell Size Control and Its Impact on Tumour Cell Function.

Cell size is an important component of cell morphological characteristics. It reflects the characteristics of the cell type, nutritional status, growth stage and physiological function. The cell size of cells of the same type tends to be homogeneous and stable. However, in tumour cells, mutations in cell cycle genes and cytoskeletal genes and overexpression of the corresponding signalling pathways often lead to large variations in tumour cell size. Tumour cells regulate cell size and growth and proliferation through multiple signalling pathways, such as PI3K/Akt/mTOR, Myc and Hippo pathways, w

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… External mechanical forces, such as compression, cause nuclear pores to allow more small molecules, including YAP, to pass through. …

Porphyromonas gingivalis поощряет передачу Т-клеток через канал сигнала NF-_B/CXCR3 в экспериментальном аутоиммунном энцефаломиелите.

Множественный склероз (MS) является хроническим аутоиммунным заболеванием центральной нервной системы (CNS); его моделью является экспериментальный аутоиммунный энцефаломиелит (EAE). Периодонтит с участием Porphyromonas gingivalis (P. gingivalis) был связан с MS и продемонстрировал, что он усугубляет EAE, однако механизмы остаются неясными. МЕТОДЫ: Мыши были случайны four группы (n = 8): контроль, только периодонтит, только EAE и EAE с периодонитом. Ежедневно проводилась оценка неврологического дефицита. Спинальный CD4+ и CD4+CXCR3+ T-фильтрация и активация NF-_B были оценены иммунофлюоресценц

Design and Preclinical Validation of an Anti-B7-H3-Specific Radiotracer: A Non-Invasive Imaging Tool to Guide B7-H3-Targeted Therapies.

Background: B7-H3, an immunoregulatory protein of the B7 family, has been associated with both anti-cancer immunity and tumor promotion, with its expression commonly correlated with poor prognosis. Although it is frequently expressed across cancers, its heterogeneity may limit the effectiveness of B7-H3-targeted therapies. Consequently, a sensitive and non-invasive method is needed to assess B7-H3 expression for patient selection and stratification. Single-domain antibody fragments (sdAbs) offer a promising platform for developing such a diagnostic tool. Methods: To generate B7-H3 sdAbs, two I

Oncogenic influences of neurotrophin receptors: Shedding light on Trk biology.

During critical stages of neurodevelopment, tropomyosin receptor kinase receptors, encoded by NTRK genes, exhibit temporally driven differential peaks of expression to properly guide the establishment of the peripheral and central nervous systems. In addition, these neuronal systems exhibit non-canonical regulation of surrounding tissues, impacting organogenesis, homeostasis, plasticity, and regeneration. The same processes that guide neurodevelopment, such as differentiation, plasticity, and neuronal survival, are also hijacked in cancer, making the NTRK family an ideal candidate to study. Th

RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges.

G protein-coupled receptors (GPCRs) are the major targets of existing drugs for a plethora of human diseases and dominate the pharmaceutical market. However, over 50% of the GPCRs remain undruggable. To pursue a breakthrough and overcome this situation, there is significant clinical research for developing RNA-based drugs specifically targeting GPCRs, but none has been approved so far. RNA therapeutics represent a unique and promising approach to selectively targeting previously undruggable targets, including undruggable GPCRs. However, the development of RNA therapeutics faces significant cha

Towards a New Dawn for Neuro-Oncology: Nanomedicine at the Service of Drug Delivery for Primary and Secondary Brain Tumours.

(1) Background/Objectives: Primary and secondary brain tumours often hold devastating prognoses and low survival rates despite the application of maximal neurosurgical resection, and state-of-the-art radiotherapy and chemotherapy. One limiting factor in their management is that several antineoplastic agents are unable to cross the blood-brain barrier (BBB) to reach the tumour microenvironment. Nanomedicine could hold the potential to become an effective means of drug delivery to overcome previous hurdles towards effective neuro-oncological treatments. (2) Methods: A scoping review following th

Перекресток между диабетом и болезнью Альцгеймера: Молекулярная перспектива.

Общемировая распространенность видов 2 Заболевание сахарным диабетом (T2DM) и болезнью Альцгеймера (AD) значительно возрастает в зависимости от возраста. Растущие данные подтверждают концептуализацию АД как типа 3 диабет, термин, предлагаемый для описания метаболического заболевания, вызванного главным образом поврежденной инсулиновой сигнализацией и инсулиновой резистентностью в мозге. В рамках этого обзора изучаются общие молекулярные механизмы, лежащие в основе как T2DM, так и AD, включая хроническую нейроинфламму, окислительный стресс, митохондриальную дисфункцию и поврежденный метаболизм

Development and characterization of chimeric antigen receptor macrophages for amyloid clearance.

Systemic amyloidosis is a protein folding disorder characterized by the extracellular deposition of protein fibrils in tissues and vital organs, leading to dysfunction and mortality. While there are monoclonal antibody-based therapies that promote cell-mediated amyloid clearance in various stages of clinical development, there are currently no treatment options which focus on reducing the tissue amyloid burden. Therefore, the urgent need for a transformative approach to facilitate amyloid clearance and restore organ function remains paramount. We demonstrate that a short, polybasic peptide (p5

RANKL Drives Bone Metastasis in Mammary Cancer: Protective Effects of Anti-Resorptive Treatments.

Receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and bone resorption, in osteolytic conditions such as osteoporosis and bone metastases. However, its role in metastasis progression remains incompletely understood. Herein, we examined whether the overexpression of human RANKL in transgenic mice (TgRANKL) affects their susceptibility to breast cancer bone metastasis compared to their wild-type (WT) littermates. Bone metastasis was induced by injecting EO771 mouse mammary adenocarcinoma cells into the caudal artery of syngeneic WT and TgRANKL mice. RANK

Role of TRP Channels in Cancer-Induced Bone Pain.

The burden of cancer is growing in almost every country. Bone metastases significantly affect the prognosis and lead to an increase in mortality and morbidity. The management of cancer-induced bone pain (CIBP) still shows various unmet needs. Opioid use is burdened by a number of possible side effects. Moreover, recent progresses in cancer treatment significantly increased the life expectancy of cancer patients, even those with metastatic disease. In this narrative review, we reported the main findings regarding TRP channel function in cancer pain models. TRP cation channels play a key role in

Рецепт 1 в диабете и его хронические осложнения: механизмы сигнализации и новые терапевтические достижения.

Диабет моллюсков (DM) — системное метаболическое расстройство, характеризующееся хронической гипергликемией, которая может оказывать воздействие на почки, сетчатку, периферийные нервы и сердечно-сосудистую систему, что в конечном счете приводит к многочисленным хроническим осложнениям. 1 (PAR1) — G-белковый рецептор, приводимый в действие через каноническое декольте, например тромбинированный декольте и неканоническое декольте, например, декольте с помощью активированного белка C или матрицы Metalloproteinase-1. Эти режимы активации инициируют различные каналы подачи сигналов вниз по течению,

Targeted phytotherapy: essential oils, multi-target cancer action & nanodelivery.

Biochemical components of essential oils (EOs) are an innovative but largely underexplored type of precision phytotherapy (PT) in oncology owing to their anticancer activity against many types of tumors. This article discusses the important multitargeted molecular mechanisms of EOs (apoptosis, cell cycle arrest, angiogenesis, metastasis, tumor microenvironment) and their role as antitumor agents. In particular, an effort has been made to emphasize on the most notable volatile EOs such as thymol, eugenol, limonene, β-caryophyllene, and their interaction with oncogenic signaling pathways (NF-κB,

Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms.

Peripheral neurologic complications are frequent adverse events during oncologic treatments and often lead to dose reduction, administration delays with time elongation of the therapeutic plan and, not least, worsening of patients' quality of life. Experience skills are required to recognize symptoms and clinical evidences and the collaboration between different health professionals, in particular oncologists and hospital pharmacists, grants a correct management of this undesirable occurrence. Some classes of drugs (platinates, vinca alkaloids, taxanes) typically develop this kind of side effe

Внеклеточные нуклеотиды являются посредником в вирусных инфекциях центральной нервной системы: ключи от нейроинфламмации и нейродегенерации.

Недавний рост инфекционных заболеваний, затрагивающих центральную нервную систему, вызвал обеспокоенность по поводу их роли в нейроинфламмации и нейродегенерации. Вирусные патогены или их продукты могут вторгаться в центральную нервную систему и вызывать повреждения, ведущие к менингиту, энцефалиту, менингоэнцефалиту, миелиту или постинфекционным демиелинизирующим заболеваниям. Хотя изначально нейроинфламмация имеет защитную функцию, хроническое воспаление может способствовать развитию нейродегенеративных заболеваний. Такие механизмы, как агрегация белков и клеточные расстройства, связаны с ко

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

Histone Modifier KANSL2 является практически осуществимым биомаркером в Мультимиломе.

Эпигенетические отклонения являются ключевыми движущими силами множественной миеломы, однако адресная терапия, использующая эпигенетические изменения, еще не установлена. Объединяя клинические и молекулярные наборы пациентов с множественной миеломой с непредвзятым генетическим экраном в vivo, мы определили подгруппу 2 (KANSL2) КАТ8, регулирующую комплекс NSL, как гистонную послетрансляционную модификацию, связанную с онкогене. Высокое выражение KANSL2 было связано с неблагоприятным прогнозом у пациентов с множественной миеломой. Генетические модели " наживы " и " потери функцион

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… Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila. Mol Cell 2006;21:811–23. 20. Ferreyra Solari NE, Belforte FS, Canedo L, Videla-Richardson GA, Espinosa JM, Rossi M, et al. …

Interleukin-12 sustained release system promotes hematopoietic recovery after radiation injury.

The continuous production of mature blood cell lineages is maintained by hematopoietic stem cells but they are highly susceptible to damage by ionizing radiation (IR) that induces death. Thus, devising therapeutic strategies that can mitigate hematopoietic toxicity caused by IR would benefit acute radiation syndrome (ARS) victims and patients receiving radiotherapy. Herein, we describe the preparation of an injectable hydrogel formulation based on Arg-Gly-Asp-alginate (RGD-Alg) and Laponite using a simple mixing method that ensured a slow and sustained release of interleukin-12 (IL-12) (RGD-Al

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

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Ion channels and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy; cause and effect?

AbstractCancer is the second leading cause of death worldwide and is a major global health burden. Significant improvements in survival have been achieved, due in part to advances in adjuvant antineoplastic chemotherapy. The most commonly used antineoplastics belong to the taxane, platinum, and vinca alkaloid families. While beneficial, these agents are frequently accompanied by severe side effects, including chemotherapy-induced peripheral neuropathy (CPIN). While CPIN affects both motor and sensory systems, the majority of symptoms are sensory, with pain, tingling, and numbness being the pre