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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

The role of RANK-ligand inhibition in cancer: the story of denosumab.

The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Deno

Therapeutic Targeting of BRD4 in Head Neck Squamous Cell Carcinoma.

The bromodomain and extraterminal family members are epigenetic readers and transcriptional coactivators which are critically involved in various biological processes including tumorigenesis. BRD4 has been increasingly appreciated as a key oncogene and promising anticancer target. Here, we sought to characterize the expression of BRD4 and its tumorigenic roles as well as therapeutic targeting in HNSCC. Methods: Expression of BRD4 mRNA and protein was determined by bioinformatics interrogation of publically available databases, primary HNSCC samples and 4NQO-induced HNSCC animal model. The tumo

Morpholino-driven blockade of Dkk-1 in osteosarcoma inhibits bone damage and tumour expansion by multiple mechanisms.

BackgroundOsteosarcoma (OS) is the most common primary bone malignancy. Chemotherapy plays an essential role in OS treatment, potentially doubling 5-year event-free survival if tumour necrosis can be stimulated. The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) enhances OS survival in part through upregulation of aldehyde-dehydrogenase-1A1 which neutralises reactive oxygen species originating from nutritional stress and chemotherapeutic challenge.MethodsA vivo morpholino (DkkMo) was employed to block the expression of Dkk-1 in OS cells. Cell mitosis, gene expression and bone destruction were meas

Recent advances in the management of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease presenting highly heterogeneous clinical manifestations and multi-systemic involvement. Patients are susceptible to relapse- and remission, thus making management challenging. Moreover, a considerable number of side effects may occur with conventional therapies; therefore, there is clearly a need for new therapeutic strategies. Since the pathogenesis of SLE is highly complex, it is far from being fully understood. However, greater understanding of the pathways and of the cellular and molecular mediators involved in SLE is being

Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service.

Emerging from the depths of evolution, pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors (i.e., PAC1, VPAC1, VPAC2) are present in multicellular organisms from Tunicates to humans and govern a remarkable number of physiological processes. Consequently, the clinical relevance of PACAP systems spans a multifaceted palette that includes more than 40 disorders. We aimed to present the versatility of PACAP1-38 actions with a focus on three aspects: (1) when PACAP1-38 could be a cause of a malfunction, (2) when PACAP1-38 could be the cure for a malfunction, and (3) when PA

NK3.3-Derived Extracellular Vesicles Penetrate and Selectively Kill Treatment-Resistant Tumor Cells.

Cancer treatments often become ineffective due to the development of tumor resistance, leading to metastasis and relapse. Treatments may also fail because of their inability to access cells deep within the tumor tissue. When this occurs, new therapeutic agents are needed. We previously reported that NK3.3EVs, extracellular vesicles (EVs) derived from the normal human natural killer (NK) cell line, NK3.3, have strong cytotoxic activity against leukemia and breast cancer cell lines, without harming normal cells. Here, we used a three-dimensional (3D) MCF7 breast cancer mammosphere model to repro

Minimizing MRONJ after Tooth Extraction in Cancer Patients Receiving Bone-Modifying Agents.

BACKGROUND: Medication-related osteonecrosis of the jaws (MRONJ) is a mucosal lesion of the maxillofacial region with necrotic bone exposure. MRONJ is believed to be multifactorial. Tooth extraction is debatably a risk factor for MRONJ. The targets of the present study were to examine MRONJ occurrence in patients using bone modifying agents (BMAs) for oncology indications and undergoing a dental extraction, and to assess whether suspected predisposing factors can predict MRONJ. MATERIALS AND METHODS: This retrospective, cohort study included all patients fitting the inclusion criteria and a l

Совпадение в полном тексте источника
… Several other medications, such as tyrosine kinase inhibitors, monoclonal antibodies (including tocilizumab), mammalian target of rapamycin inhibitors, radiopharmaceuticals, selective estrogen receptor modulators, and immunosuppressants, have also been implicated in osteonecrosis of the jaws [ 9 ]. …

Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment.

Currently, chemotherapy is the main treatment for tumors, but there are still problems such as unsatisfactory chemotherapy results, susceptibility to drug resistance, and serious adverse effects. Natural compounds have numerous pharmacological activities which are important sources of drug discovery for tumor treatment. The combination of chemotherapeutic drugs and natural compounds is gradually becoming an important strategy and development direction for tumor treatment. In this paper, we described the role of natural compounds in combination with chemotherapeutic drugs in synergizing, reduci

Application of single-cell and spatial omics in deciphering cellular hallmarks of cancer drug response and resistance.

Drug resistance poses a significant challenge in cancer therapy, contributing to rapid recurrence, disease progression, and high patient mortality. Despite its critical impact, few reliable predictors for cancer drug response or failure have been established for clinical application. Tumor heterogeneity and the tumor microenvironment (TME) are pivotal factors influencing cancer drug efficacy and resistance. Tumor heterogeneity leads to variable therapeutic responses among patients, while dynamic interactions between cancer cells and the TME enhance tumor survival and proliferation, underscorin

Дисфункция мозгового барьера (BBB) в заболеваниях CNS: уделение внимания перицитам.

Дизфункция мозгового барьера (BBB) является важным патологическим механизмом в заболеваниях центральной нервной системы (CNS) и может вызвать ряд патологических реакций, таких, как нейроинфламмационная реакция, окислительный стресс, иммунная инфильтрация и т.д., что усугубляет повреждение мозга. Вместе с тем исследователи часто игнорируют перициты, и ни одно обзорное исследование пока еще не подытожило механизм, с помощью которого перициты способствуют дисфункции ББД в заболеваниях КНС.Поэтому в настоящем обзоре изучается патофизиология дисфункции ББД в связи с заболеваниями КНС и содержится п

Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, December 5th 2015

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Exploring the Therapeutic Potential of Ganoderma lucidum in Cancer.

Triterpenoids, such as ganoderic acid, and polysaccharides, including β-D-glucans, α-D-glucans, and α-D-mannans, are the main secondary metabolites of the medicinal fungus Ganoderma lucidum. There is evidence of the effects of ganoderic acid in hematological malignancies, whose mechanisms involve the stimulation of immune response, the macrophage-like differentiation, the activation of MAP-K pathway, an IL3-dependent cytotoxic action, the induction of cytoprotective autophagy, and the induction of apoptosis. In fact, this compound has been tested in twenty-six different human cancer cell types

Study of a novel Ca/P/S-based cement implanted in the osteoporotic goat spine and its clinical application in preventing adjacent vertebral fractures.

Osteoporotic vertebral compression fracture (OVCF) has been increasing over the last decades. In addition to primary OVCF, the adjacent vertebral fracture (AVF) is a frequent serious complication in OVCF patients receiving percutaneous vertebroplasty or kyphoplasty, resulting in poor long-term outcome and recurrent symptoms. The aim of the present study is to investigate the bone regeneration behavior of a novel Ca/P/S-based resorbable cement (Ezechbone® Cement CBC-400) implanted into surgically created vertebral defects of ovariectomized (OVX) goats. Furthermore, the present study provides a

Concurrent whole brain radiotherapy and bortezomib for brain metastasis.

BackgroundSurvival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis.MethodsA phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m2) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the

Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis.

Breast cancer mainly spreads to bone, causing decreased survival of patient. Human antigen R (HuR) and chemokines are important molecules associated with mRNA stability and cell-cell interaction in cancer biology. Here, HuR knockdown inhibited bone metastasis and osteolysis of metastatic breast cancer cells in mice and HuR expression promoted the metastatic ability of cancer cells via CCL20 and GM-CSF. In contrast with the findings for GM-CSF, ELAVL1 and CCL20 expressions were markedly increased in breast tumor tissues and ELAVL1 expression showed a strong positive correlation with CCL20 expre

Molecular Mechanisms Leading from Periodontal Disease to Cancer.

Periodontitis is prevalent in half of the adult population and raises critical health concerns as it has been recently associated with an increased risk of cancer. While information about the topic remains somewhat scarce, a deeper understanding of the underlying mechanistic pathways promoting neoplasia in periodontitis patients is of fundamental importance. This manuscript presents the literature as well as a panel of tables and figures on the molecular mechanisms of Porphyromonas gingivalis and Fusobacterium nucleatum, two main oral pathogens in periodontitis pathology, involved in instigati

New landscapes and horizons in hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC), is the sixth most frequent form of cancer and leads to the fourth highest number of deaths each year. HCC results from a combination of environmental factors and aging as there are driver mutations at oncogenes which occur during aging. Most of HCCs are diagnosed at advanced stage preventing curative therapies. Treatment in advanced stage is a challenging and pressing problem, and novel and well-tolerated therapies are urgently needed. We will discuss further advances beyond sorafenib that target additional signaling pathways and immune checkpoint proteins. The

Роль и диагностическая значимость Аполипопротеина D в отдельных нейродегенеративных расстройствах.

Всемирная организация здравоохранения в 2021 году назвала болезнь Альцгеймера и другие слабоумия седьмой по величине причиной смерти во всем мире. Нейродегенеративные расстройства являются прогрессивными, трудноразрешимыми и часто смертельными. Ранняя диагностика может дать пациентам возможность долго выжить с ослабленной симптоматологией из-за раннего вмешательства. Поэтому необходимы дальнейшие исследования по поиску неинвазивных биомаркеров нейродегенеративных заболеваний. Apopoprotein D (ApoD) — гликпротеин, содержащийся в липидном метаболизме, регулировании окислительного стресса и воспал

Апиген как потенциальный модулятор нейроинфламмации в многоразовом склерозе: обзор.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы (CNS), характеризующееся нейроинфламмацией и обезвоживанием. Несмотря на то, что в течение последнего десятилетия расширились возможности лечения MS, нынешняя терапия направлена главным образом на периферийные иммунные системы и часто связана со значительными побочными эффектами. Кроме того, эта терапия до сих пор не предлагает решений для последующего нейродегенерации, сопровождающего развитие болезни. Результаты исследований, проведенных с использованием клеточных и животных моделей и исследований