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Tumor Whole-Genome Sequencing for Prediction of Venous Thromboembolism in Patients With Metastasized Solid Cancer.

BACKGROUND: International guidelines suggest prophylactic anticoagulation for patients with cancer at high risk of venous thromboembolism (VTE). Here, we evaluated whether tumor whole-genome sequencing data may improve the selection of high-risk patients. METHODS: In a pan-cancer cohort of 3087 patients, associations of candidate clinical predictors, the germline extended 297-single nucleotide polymorphism polygenic risk score, tumor mutational characteristics, and somatic tumor mutations with VTE were estimated by calculating hazard ratios (HRs). RESULTS: During 12-month follow-up, 237 (7.7

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… Pan-cancer landscape of homologous recombination deficiency. Nat Commun. 2020;11:5584. doi: 10.1038/s41467-020-19406-4 41. Pruis MA, Groenendijk FH, Badloe KS, van Puffelen A, Robbrecht D, Dinjens WNM, Sleijfer S, Dingemans AMC, von der Thüsen JH, Roepman P, et al. …

Необычная реакция профилей белков HERV-W в множестве склерозов: потенциальные биомаркеры для развития заболеваний.

ВВЕДЕНИЕ: Протеины конверта syncytin-1 и fHERV-W из эндогенной ретровирусной семьи человека "W" (HERV-W) были определены в качестве потенциальных факторов риска при множественном склерозе (MS). Цель этого исследования заключается в оценке как юморальной, так и клеточной иммунной реакции на антигенные пептиды, получаемые из этих белков, в различных клинических формах и фазах МУ. МЕТОДЫ: Косвенный анализ иммуносорбента, связанного с ферментом (ELISA), использовался для измерения ответов на иммуноглобулин G (IgG) syncytin-1env 486-500 и fHERV-Wenv 486-504 Пептиды у пациентов с склерозом. Дискрими

Consensus on the Treatment and Follow-Up for Metastatic Castration-Resistant Prostate Cancer: A Report From the First Global Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PurposeTo present a summary of the recommendations for the treatment and follow-up for metastatic castration-resistant prostate cancer (mCRPC) as acquired through a questionnaire administered to 99 physicians working in the field of prostate cancer in developing countries who attended the Prostate Cancer Consensus Conference for Developing Countries.MethodsA total of 106 questions out of more than 300 questions addressed the use of imaging in staging mCRPC, treatment recommendations across availability and response to prior drug treatments, appropriate drug treatments, and follow-up, and those

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… Currently, FDA approved in 2020 olaparib and rucaparib, two poly ADP ribose polymerase inhibitors for adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer (mCRPC), which have progressed …

Tripchlorolide induces autophagy in lung cancer cells by inhibiting the PI3K/AKT/mTOR pathway and improves cisplatin sensitivity in A549/DDP cells.

Tripchlorolide (T4) has been shown to induce A549 lung cancer cell death predominantly by activating an autophagy pathway. However, the underlying mechanism remains unclear. Herein, we demonstrated that compared with T4 treatment alone, pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase), perifosine (an inhibitor of AKT) or rapamycin (an inhibitor of mTOR) combined with a subsequent T4 treatment significantly impaired the cell viability of A549 and A549/DDP lung cancer cells. We found that either treatment scheme markedly reduced the activity of P13K and AKT. Expressio

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

Advances and development of prostate cancer, treatment, and strategies: A systemic review.

The most common type of cancer in the present-day world affecting modern-day men after lung cancer is prostate cancer. Prostate cancer remains on the list of top three cancer types claiming the highest number of male lives. An estimated 1.4 million new cases were reported worldwide in 2020. The incidence of prostate cancer is found predominantly in the regions having a high human development index. Despite the fact that considerable success has been achieved in the treatment and management of prostate cancer, it remains a challenge for scientists and clinicians to curve the speedy advancement

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… To date mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, and CHEK2) are potentially associated with PC. 2.3.2 Modifiable risk factors 2.3.2.1 Obesity Overweight and obesity are complex diseases involving an excessive amount of body fat …

Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment.

BackgroundRibonucleotide reductase (RR) is a key enzyme in tumor proliferation, especially its subunit-RRM2. Although there are multiple therapeutics for tumors, they all have certain limitations. Given their advantages, traditional Chinese medicine (TCM) monomers have become an important source of anti-tumor drugs. Therefore, screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development.AimTo screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2.MethodsThe Gene Expression Profiling Interactive An

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… Berberine radiosensitizes human esophageal cancer cells by downregulating homologous recombination repair protein RAD51. PLoS One. 2011;6:e23427. doi: 10.1371/journal.pone.0023427. 15. Tillhon M, Guamán Ortiz LM, Lombardi P, Scovassi AI. Berberine: new perspectives for old remedies. …

Современные методы диагностики медицинских паразитов и артроподов

Обычные методы, такие, как микроскопия, используются для диагностики паразитических заболеваний и медицинских заболеваний, связанных с артроподами, на протяжении многих лет. Некоторые методы считаются золотыми. Однако их ограниченная чувствительность, специфичность и точность, а также потребность в дорогостоящих реагентах и высококвалифицированных технических специалистах являются критическими проблемами. В этой связи постоянно разрабатываются новые инструменты для уменьшения числа проблем. Недавно three Возникли самые современные методы: штрих-кодирование ДНК, геометрические морфометры и иску

Тригеминальный контакт с артерией у людей, не имеющих тригеминиальной нейронгии - исследование MR.

Основная цель этого исследования состоит в том, чтобы предложить новую нервную сеть, названную BrainNeXt, для автоматизированного обнаружения расстройств мозга с использованием изображений магнитного резонанса (MRI). Кроме того, мы намерены изучить функционирование нашей предлагаемой сети по различным видам медицинского применения. Для обеспечения эффективности классификации изображений с высоким/громким изображением мы собрали новый набор данных МРТ, принадлежащих four Классы:1Болезнь Альцгеймера,2) хроническая ишемия,3) множественный склероз и ()4) контроль. Вдохновленные ConvNeXt, мы спроек

Cellular immunotherapy in melanoma: the next frontier in cancer treatment.

Therapy-resistant melanoma remains a major clinical challenge despite advances with immune checkpoint inhibitors and targeted therapies, as most patients ultimately exhibit primary or acquired resistance and progress through multiple toxic treatment lines with limited durable benefit. This resistance reflects not only T-cell dysfunction but also a profound quantitative deficit of tumor-reactive lymphocytes, compounded by myeloid- and Treg-mediated immunosuppression, impaired antigen presentation, and tumor dedifferentiation programs generating a cold tumor microenvironment. Cellular immunother

Виром ДНК связан с аутоиммунными заболеваниями и COVID-19.

Аберрантная иммунная реакция на вирусные патогены способствует патогенезу, но наше понимание патологических иммунных реакций, вызванных вирусами в вироме человека, особенно в масштабе населения, остается ограниченным. Мы проанализировали наборы данных о последовательности целых генов 6,321 Японцы, включая пациентов с аутоиммунными заболеваниями (псориаз вульгарис, ревматоидный артрит (RA), системный волшебный эритематос (SLE), легочный альвеолярный протеиноз (PAP) или множественный склероз) и коронавирусное заболевание 2019 (В тыс.COVID-19) или здоровый контроль. Систематическая количественная

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients' outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs hav

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… Similarly, a selective targeting of homologous recombination (HR) repair pathways, leading to decreased expression levels of DNA-repair proteins Rad51 and Mre11, has been recently described for the combination VPA-AZD2461, a PARP inhibitor [ 158 ]. …

Gaucher disease: the hematologist's perspective of a multisystemic disorder.

Gaucher disease (GD) exemplifies how a single genetic mutation can give rise to a complex multisystem disorder with profound hematological implications. Central to its pathophysiology is the lysosomal accumulation of glucosylceramide due to deficient glucocerebrosidase activity, together with abnormal folding and trafficking of the enzyme that induce endoplasmic reticulum stress and cellular dysfunction. These processes disrupt reticuloendothelial homeostasis and interfere with hematopoiesis. As a consequence, macrophage activation and chronic inflammation contribute to the cytopenias, splenom

The application, safety, and future of ex vivo immune cell therapies and prognosis in different malignancies.

IntroductionImmunotherapy has revolutionized how cancer is treated. Many of these immunotherapies rely on ex vivo expansion of immune cells, classically T cells. Still, several immunological obstacles remain, including tumor impermeability by immune cells and the immunosuppressive nature of the tumor microenvironment (TME). Logistically, high costs of treatment and variable clinical responses have also plagued traditional T cell-based immunotherapies.MethodsTo review the existing literature on cellular immunotherapy, the PubMed database was searched for publications using variations of the phr

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… Following isolation, the T cells will undergo ex vivo genetic modification through various routes including mRNA transfection, viral vectors, transposons, or homologous recombination. 23 Following genetic modification, the T cells will be expanded ex vivo . …

EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation.

Advanced therapy medicinal products (ATMPs) require evaluation by the European Medicines Agency's Committee for Advanced Therapies prior to being placed on the European market, subject to a Marketing Authorisation granted by the European Commission. In common with other medicinal products, various regulatory pathways are available for taking ATMPs through clinical trials to market authorisation, and the regulatory pathway taken will depend on a product's characteristics and the target patient population. With the industry poised to deliver more late-stage clinical and commercial ATMPs for seri

Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma.

Pancreatic adenocarcinoma (PAC) is one of the most deadly malignant neoplasms, and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis, as well as tumor development, invasion, and metastasis in PAC. Thus, immunosuppression-related signaling, especially that involving immune checkpoint and inflammation, has emerged as novel treatment targets for PAC. However, PAC is an immune-resistant tumor, and it is still unclear whether immune checkpoint or anti-inflammatio

Smart Targeting To Improve Cancer Therapeutics.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loade

Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era.

Chronic lymphocytic leukemia is a lymphoproliferative disorder marked by the expansion of monoclonal, mature CD5+CD23+ B cells in peripheral blood, secondary lymphoid tissues, and bone marrow. The disease exhibits significant heterogeneity, with numerous somatic genetic alterations identified in the neoplastic clone, notably mutated TP53 and immunoglobulin heavy chain mutational statuses. Recent studies emphasize the pivotal roles of genetics and patient fragility in treatment decisions. This complexity underscores the need for a personalized approach, tailoring interventions to individual gen

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra

Translational Advances in Oncogene and Tumor-Suppressor Gene Research.

Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes-tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival-can help to unde