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Single-cell sequencing in molecular diagnostics: Transformative yet untapped potential.

Single-cell sequencing (SCS) techniques have the potential to offer precise insights into cellular diversity by revealing unique genetic and transcriptomic profiles at the single-cell level. This advanced technology has been used extensively in research, but it has still not translated to clinical diagnostics, despite its potential. SCS provides more accurate granular information about heterogeneous cell populations and the creation of personalized treatment strategies. However, the integration of SCS into clinical practice is challenging. This review discusses the potential of SCS technologie

Компьютерный подход к разработке лекарственных средств для множественного склероза с помощью модели QSPR, теории химических графиков и анализа решений по нескольким критериям.

Множественный склероз (MS) — сложное аутоиммунное заболевание центральной нервной системы с неизвестной этиологией. Несмотря на то, что медикаментозная терапия может замедлить прогресс, существует необходимость в более эффективном лечении. Модель количественного соотношения структуры и активности (QSAR) с использованием топографических индексов, полученных на основе теории химических графиков, является многообещающим подходом к рациональному проектированию новых лекарств для MS. Используя подход линейной регрессии, мы создаём модели количественного соотношения структуры и производительности (Q

Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib.

Proteasomal inhibition revolutionized myeloma therapies in this decade of novel agents. The only US Food and Drug Administration approved proteasome inhibitor so far, bortezomib effectively targets the constitutive proteasome subunit β5 of the 26S proteasome. Bortezomib induces high and quality response rates that are durable. However, myeloma cells acquire resistance to bortezomib through various mechanisms. Further, grade 3/4 peripheral neuropathy is seen in up to a quarter of patients treated with bortezomib. While the recent change in the mode of administration via the subcutaneous route i

Targeting strategies for bone diseases: signaling pathways and clinical studies.

Since the proposal of Paul Ehrlich's magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has b

Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study.

BackgroundGlioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O6 methylguanine DNA methyltransferase (MGMT) that renders the tumors resistant to temozolomide (TMZ). We hypothesized that pretreatment with bortezomib (BTZ) 48 hours prior to TMZ to deplete MGMT levels would be safe and tolerated by patients with recurrent GBM harboring unmethylated MGMT promoter. The secondary objective was to investigate whether 26S proteasome blockade may enhance differentia

A Systematic Review of the Effects of Bisphosphonates on Osteoblasts In Vitro.

Bisphosphonates (BPs) are widely used to treat bone disorders, prevent skeletal-related events, and manage bone metastasis. These drugs are synthetic analogs of pyrophosphate and primarily function by inhibiting osteoclast activity. However, increasing evidence suggests that they also have an effect on osteoblasts. This systematic review aims to evaluate how bisphosphonates affect osteoblasts by summarizing findings from in vitro studies on the impact of BPs on osteoblast lineage cells, addressing the following question: "Do bisphosphonates affect osteoblast cell lineage function?". For this p

Neuroimaging and Neurocognitive Outcomes in Older Patients with Multiple Myeloma Treated with Chemotherapy and Autologous Stem Cell Transplantation.

There is a paucity of research on treatment-related neurotoxicity in older adults with multiple myeloma (MM) treated with high-dose chemotherapy (HDC) and autologous SCT (HDC/ASCT), despite the increasing use of this regimen. We examined resting state functional connectivity (RSFC), gray matter (GM) volume, neurocognitive function (NF), and proinflammatory cytokines (PCy) in older patients with MM pre- and post-HDC/ASCT. Eighteen patients underwent MRI, NF tests, and serum PCy measurements prior to HDC/ASCT, and fifteen patients completed a follow up five-months post-HDC/ASCT. There were signi

Protocol for SARS-CoV-2 post-vaccine surveillance study in Australian adults and children with cancer: an observational study of safety and serological and immunological response to SARS-CoV-2 vaccination (SerOzNET).

BackgroundCancer is associated with excess morbidity and mortality from coronavirus disease 2019 (COVID-19) following infection by the novel pandemic coronavirus SARS-CoV-2. Vaccinations against SARS-CoV-2 have been rapidly developed and proved highly effective in reducing the incidence of severe COVID-19 in clinical trials of healthy populations. However, patients with cancer were excluded from pivotal clinical trials. Early data suggest that vaccine response is less robust in patients with immunosuppressive conditions or treatments, while toxicity and acceptability of COVID-19 vaccines in th

The 'speck'-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis.

The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a single supramolecular punctum, known as a speck, per cell, which is the site where the pro-inflammatory cytokines IL-1β and IL-18 are converted into their bioactive form. Speck also provides the platform for gasdermin D protein activation, whose N-terminus domain perforates the plasma membrane, allowing the release of mature cytokines alongside with a highly inflammatory form of cell death

Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer.

Uncontrolled proliferation is a feature defining cancer and it is linked to the ability of cancer cells to effectively adapt their metabolic needs in response to a harsh tumor environment. Metabolic reprogramming is considered a hallmark of cancer and includes increased glucose uptake and processing, and increased glutamine utilization, but also the deregulation of lipid and cholesterol-associated signal transduction, as highlighted in recent years. In the first part of the review, we will i) provide an overview of the major types of lipids found in eukaryotic cells and their importance as med

The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.

Cancer development and progression are increasingly understood to arise from dynamic interactions between genetic alterations and environmentally driven epigenetic regulation, with dietary exposures representing one of the most biologically influential and modifiable factors. Given the expanding evidence linking nutrition to epigenomic remodeling, a comprehensive synthesis of how specific dietary components influence cancer-relevant epigenetic mechanisms is needed to clarify their preventive and therapeutic relevance. This review brings together mechanistic, epidemiologic, and translational fi

Протеомический анализ показывает дисрегламентацию периферийных нейтрофилов крови у пациентов с множественным склерозом.

Множественный склероз (MS) представляет собой сложное автовоспалительное заболевание мозга и спинного мозга, которое приводит к аксоновому демилеляции и симптомам, включая усталость, боль и трудности с зрением и мобильностью. Вовлеченность иммунной системы в патологию MS хорошо известна, в частности адаптивная реакция T-клеток, и особое внимание уделяется производящему IL-17 поднабору клеток TH17 и их роли в вождении болезней. Однако важность врожденных иммунных клеток не была столь хорошо охарактеризована. Здесь мы сосредоточили внимание на нейтрофилах, которые являются врожденными иммунными

Терапевтическая ориентация на нейроинфламацию, вызванную ожирением, и нейродегенерацию.

Ожирение является одним из основных из изменяемых факторов риска, ведущих к нейроинфламмации и нейродегенерации. Чрезмерное содержание жира в ожирении способствует постепенному проникновению иммунных клеток в жировые ткани, что приводит к высвобождению провоспалительных факторов, таких, как цитокины и адипокины. Эти подстрекательские посредники циркулируют по кровотоку, пропагандируя воспаление как на периферии, так и в центральной нервной системе. Гут дисбиоз, который приводит к утечке кишечного барьера, усугубляет воспаление и играет важную роль в увязке ожирения с патогенезом нейроинфламмац

Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results.

There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50

The roles of inflammasomes in cancer.

Inflammation is a key characteristic of all stages of tumor development, including tumor initiation, progression, malignant transformation, invasion, and metastasis. Inflammasomes are an important component of the inflammatory response and an indispensable part of the innate immune system. Inflammasomes regulate the nature of infiltrating immune cells by signaling the secretion of different cytokines and chemokines, thus regulating the anti-tumor immunity of the body. Inflammasome expression patterns vary across different tumor types and stages, playing different roles during tumor progression

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation.

Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is associated with non-relapse mortality (NRM) and quality of life (QOL). Multiple factors may contribute to AKI during allo-HCT and are often present at the same time making it difficult to determine the cause of AKI in each patient. Nephrotoxic drugs, infections, thrombotic microangiopathy (TMA), and sinusoidal obstruction syndrome (SOS) are well described causes of AKI during allo-HCT. Acute graft-versus-host disease (aGVHD) is a major complication of allo-HCT that mainly targe

The Role of Interleukin-1 in the Pathogenesis of Cancer and its Potential as a Therapeutic Target in Clinical Practice.

Interleukin-1 (IL-1) has long been known to be a key mediator of immunity and inflammation. Its dysregulation has been implicated in recent years in tumorigenesis and tumor progression, and its upregulation is thought to be associated with many tumors. Overexpression of the IL-1 agonists IL-1α and IL-1β has been shown to promote tumor invasiveness and metastasis by inducing the expression of angiogenic genes and growth factors. IL-1 blockers such as anakinra and canakinumab are already approved and widely used for the treatment of some autoimmune and autoinflammatory diseases and are currently

TACC3, correlated with immune cell infiltrates, is a novel prognostic biomarker in BRCA.

Transforming acidic coiled-coil-containing protein 3 (TACC3) plays a crucial oncogenic role in various carcinomas and may act as a novel prognostic factor. However, its prognostic significance and underlying mechanisms in breast cancer (BRCA) remain unclear and require further investigation. This research included 181 breast cancer tissues, and the expression levels of TACC3 were analyzed by immunohistochemistry staining and grading. The mRNA expression of TACC3 in pan-cancer was analyzed with The Cancer Genome Atlas data platform. Receiver operating characteristic curve analysis assessed TACC

Использование подкожного дородового ухода - окончательные результаты невмешательского, наблюдательного исследования (SISTER) в Германии и Австрии.

Натальизумаб является лекарственной терапией для пациентов с повторно излучающимся множественным склерозом (RRMS). Помимо его первоначальной формы внутривенного (IV) использования был утвержден подкожный (SC) маршрут управления (ROA) 2021. Впоследствии в Германии и Австрии было начато исследование с целью получения реальных данных об использовании, предпочтениях пациентов, безопасности и эффективности врачебной практики. ЦЕЛИ: Основная цель заключалась в том, чтобы сравнить предпочтения пациентов в пользу РВ и удовлетворенность с СО. IV Натенизумаб на базовом уровне и до 12 месяцев лечения. Вт

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… The most recent treatments prior to study entry included the following DMTs (if administered to ≥5.0% of patients): glatiramer acetate 15.8% (n=49), fingolimod: 14.8% (n=46), dimethyl fumarate: 13.9% (n=41), teriflunomide: 7.7% (n=24), interferon beta-1a SC): 7.7% (n=22), and interferon-beta-1a intramuscular …

CAR T-Cell Therapy for Cancer: Latest Updates and Challenges, with a Focus on B-Lymphoid Malignancies and Selected Solid Tumours.

Although exponential progress in treating advanced malignancy has been made in the modern era with immune checkpoint blockade, survival outcomes remain suboptimal. Cellular immunotherapy, such as chimeric antigen receptor T cells, has the potential to improve this. CAR T cells combine the antigen specificity of a monoclonal antibody with the cytotoxic 'power' of T-lymphocytes through expression of a transgene encoding the scFv domain, CD3 activation molecule, and co-stimulatory domains. Although, very rarely, fatal cytokine-release syndrome may occur, CAR T-cell therapy gives patients with ref