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Peripheral neuropathy associated with monomethyl auristatin E-based antibody-drug conjugates.

Since the successful approval of gemtuzumab ozogamicin, antibody-drug conjugates (ADCs) have emerged as a pivotal category of targeted therapies for cancer. Among these ADCs, the use of monomethyl auristatin E (MMAE) as a payload is prevalent in the development of ADC drugs, which has significantly improved overall therapeutic efficacy against various malignancies. However, increasing clinical observations have raised concerns regarding the potential nervous system toxicity associated with MMAE-based ADCs. Specifically, a higher incidence of peripheral neuropathy has been reported in ADCs inco

Innovative laboratory techniques shaping cancer diagnosis and treatment in developing countries.

Cancer is a major global health challenge, with approximately 19.3 million new cases and 10 million deaths estimated by 2020. Laboratory advancements in cancer detection have transformed diagnostic capabilities, particularly through the use of biomarkers that play crucial roles in risk assessment, therapy selection, and disease monitoring. Tumor histology, single-cell technology, flow cytometry, molecular imaging, liquid biopsy, immunoassays, and molecular diagnostics have emerged as pivotal tools for cancer detection. The integration of artificial intelligence, particularly deep learning and

CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.

Several landmark studies over the past decade have uncovered a critical role of the CRL3KBTBD4 ubiquitin ligase complex in regulating stability of corepressor of repressor element 1 silencing transcription factor (CoREST) complex proteins and normal hematopoietic stem cell self-renewal. There is now mounting evidence that the CoREST complex plays oncogenic roles, although the contributions of its catalytic versus noncatalytic functions remain unclear. Here, we summarize and discuss mechanisms whereby the CoREST complex coopts tissue-specific transcription factors to elicit pathogenic activity

A comprehensive review on pain: Model, target, therapy, and prospect (Review).

Pain serves as both a protective physiological response essential for species survival and a global health issue affecting human well‑being and societal development. The present review systematically summarized and analyzed the research progresses on pain through a multidimensional analytical framework encompassing animal models, molecular targets, therapeutic approaches and future prospects. In animal modeling, neuropathic pain paradigms have evolved from traditional mechanical compression to composite models that combine dynamic displacement and chemical stimulation. Cancer‑induced pain mode

Перенос Митохондрии для ремонта миелина.

Обезвоживание является общей характеристикой нейро-воспалительных и дегенеративных заболеваний центральной нервной системы (КНС), таких, как множественный склероз (МС). Часто это связано с нарушениями межклеточной связи, биоэнергетики и метаболического баланса в сочетании с митохондриальной дисфункцией в таких клетках, как олигодендроциты, нейроны, астроциты и микроглиа. Несмотря на то, что нынешние методы лечения MS сосредоточены на иммуномодуляции, они не могут остановить или обратить вспять прогресс демиэлизации. Последние достижения подчеркивают межклеточный митохондриальный обмен в качест

CARBOMETASPINE: protocol for a multicenter, prospective, randomized controlled trial of carbonfiber spinal fixation in metastatic disease.

BACKGROUND: Spinal metastases frequently cause neurological compromise and mechanical instability. Titanium fixation limits postoperative imaging and hinders stereotactic body radiotherapy (SBRT) planning because of artefacts. METHODS: CARBOMETASPINE is a multicentre, prospective, randomised controlled trial. A total of 226 adults with unstable or epidurally infiltrating spinal metastases will be randomised 1 : 1 : 1 to: (I) carbonfibre/PEEK fixation + postoperative SBRT (5 × 5 Gy); (II) titanium fixation + postoperative SBRT; (III) preoperative SBRT + titanium fixation. The primary endpoint i

Изменения лакта и лактилации в неврологических расстройствах.

Значительное внимание стало уделяться изучению изменений в лактилации различных целевых органов как в области здравоохранения, так и в области болезней. Многие жизненно важные процессы и начало болезней связаны не только с избытком белков, но и в первую очередь регулируются различными посттрансляционными изменениями белков. Лактат, который раньше считался лишь побочным продуктом анаэробного метаболизма, превратился в важнейшую энергетическую субстрату и сигнализирующую молекулу, связанную как с физиологическими, так и патологическими процессами в нервной системе. Кроме того, в недавних исследо

The functional imperative in high-grade glioma.

Precision oncology has emerged as a promising strategy for treating high-grade gliomas, yet its clinical impact has been disappointing, with over 300 clinical trials on targeted therapies failing to yield substantial improvements in patient outcomes. Current approaches primarily focus on static, marker-driven tumor features, which capture only a small portion of the complex biology that governs therapeutic responses. Functional precision oncology (FPO) offers a complementary approach, enhancing treatment selection in a personalized manner by dynamically testing patient-derived tumor cells agai

Targeting the Cancer-Neuronal Crosstalk in the Pancreatic Cancer Microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive solid tumors with a dismal prognosis and an increasing incidence. At the time of diagnosis, more than 85% of patients are in an unresectable stage. For these patients, chemotherapy can prolong survival by only a few months. Unfortunately, in recent decades, no groundbreaking therapies have emerged for PDAC, thus raising the question of how to identify novel therapeutic druggable targets to improve prognosis. Recently, the tumor microenvironment and especially its neural component has gained increasing interest in the

Artificial intelligence in immunotherapy: revolutionizing diagnostic and therapeutic applications in cancer and autoimmune diseases.

Artificial intelligence (AI) is increasingly advancing precision immunotherapy by integrating high-dimensional biomedical data to support diagnosis, treatment selection, and longitudinal monitoring in both cancer and autoimmune diseases. This review summarizes AI applications in biomarker discovery, prediction of immune checkpoint inhibitor (ICI) response and toxicity, neoantigen prioritization, CAR-T cell optimization, and therapeutic antibody engineering. In oncology, multimodal models combining multi-omics, medical imaging, and clinical variables improve patient stratification and non-invas

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… DL architectures, including convolutional neural networks (CNNs) and recurrent neural networks (RNNs), effectively process large-scale spatial and sequential datasets, enabling the identification of complex biomarkers, such as gene expression profiles predictive of ICI responsiveness. …

Development of a Multimodal Machine Learning Model for Predicting Second Osteoporotic Vertebral Compression Fractures.

PURPOSE: Osteoporosis increases the probability of osteoporotic vertebral compression fractures (OVCF), and the resultant pain severely limits physical activity and increases mortality and morbidity. This study aimed to develop a high-precision multimodal prediction model to forecast the risk of a second OVCF. MATERIALS AND METHODS: This retrospective study included 178 patients from a single institution with a first OVCF between January 1, 2000, and December 31, 2019. The study dataset included 18 preoperative clinical variables, including demographics, medications, comorbidities, bone miner

A Comprehensive Single Institutional Review of 2 Years in a Designated Fast-Track Sarcoma Diagnostic Clinic Linked with a Sarcoma Specialist Advisory Group: Meeting the Target but Failing the Task?

Background. National guidelines prompted the implementation of a designated two-week wait referral pathway to facilitate the early diagnosis of sarcomas, to improve treatment outcomes. Methods. Patients referred to the Cambridge Sarcoma Diagnostic Clinic between January 2013 and December 2014 were identified through the electronic appointments system. Information was retrospectively retrieved about patient characteristics and details of the diagnostic pathway. Results. 17.3% of patients referred (69/397) were diagnosed with a malignancy. Of these, 59.3% (41/69) had primary sarcomas, 17.4% (12/

Targeting Non-coding RNA for Glioblastoma Therapy: The Challenge of Overcomes the Blood-Brain Barrier.

Glioblastoma (GBM) is the most malignant form of all primary brain tumors, and it is responsible for around 200,000 deaths each year worldwide. The standard therapy for GBM treatment includes surgical resection followed by temozolomide-based chemotherapy and/or radiotherapy. With this treatment, the median survival rate of GBM patients is only 15 months after its initial diagnosis. Therefore, novel and better treatment modalities for GBM treatment are urgently needed. Mounting evidence indicates that non-coding RNAs (ncRNAs) have critical roles as regulators of gene expression. Long non-coding

Artificial Intelligence Resources for the Screening of Titles and Abstracts in Systematic Reviews: A Scoping Review.

IntroductionArtificial intelligence (AI) is a branch of technology enabling machines to emulate complex human skills; it can also entail problem-solving using bioinspired methods. It is used for automating systematic literature reviews (SLR), that is, defining a clinical question, locating relevant literature, preliminary screening, study evaluation, data extraction and analysis. Title and abstract screening is one of the most time-consuming and error-prone phases involved in developing a systematic review. While AI promises to expedite this process, adopting it faces challenges due to concern

New genomic and proteomic biomarker discovery in cancer: revolutionizing diagnosis and prognostication.

Cancer remains a major global health challenge, with substantial morbidity and mortality worldwide. Advances in genomic and proteomic biomarker discovery have transformed cancer diagnosis, prognosis, and treatment selection. The evolution from early serological markers such as carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) to modern multi-omics approaches enabled by next-generation sequencing (NGS), mass spectrometry (MS), and advanced bioinformatics has revolutionized personalized medicine and targeted therapy, leading to improved outcomes. This review highlights the histo

Role of PAX6, TRPA1, BCL11B, MCOLN2, CUX1, EMX1 in colorectal cancer and osteosarcoma.

Colorectal cancer is a cancer that arises from the abnormal growth of cells in the colon or rectum. Osteosarcoma (OS) is a common primary bone tumor with high degree of malignancy. The configuration files for colorectal cancer dataset GSE142279 and OS datasets GSE197158 and GSE206448 were downloaded from Gene Expression Omnibus database using the platforms GPL20795, GPL20301, and GPL24676. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. Construction and analysis of protein-protein interactions (PPI) network. Functional

Навигатор биомаркеров человека.

Биомаркеры играют ключевую роль в современных исследованиях медицины, особенно в ранней диагностике заболеваний и персонализированном лечении. Несмотря на то, что предыдущие исследования систематически обзоры маркеров в различных областях заболеваний, интегрированная система, которая связывает основные физиологические системы, охватывает множество органов и охватывает широкий спектр заболеваний, все еще отсутствует. В контексте современных вызовов здоровья, характеризующихся высокой распространенностью хронических заболеваний и широкими сопутствующими заболеваниями, создание панорамной системы

A review on machine learning approaches and trends in drug discovery.

Drug discovery aims at finding new compounds with specific chemical properties for the treatment of diseases. In the last years, the approach used in this search presents an important component in computer science with the skyrocketing of machine learning techniques due to its democratization. With the objectives set by the Precision Medicine initiative and the new challenges generated, it is necessary to establish robust, standard and reproducible computational methodologies to achieve the objectives set. Currently, predictive models based on Machine Learning have gained great importance in t

Machine Learning for Multi-Omics Characterization of Blood Cancers: A Systematic Review.

Artificial Intelligence and machine learning are increasingly used to interrogate complex biological data. This systematic review evaluates their application to multi-omics for the molecular characterization of hematological malignancies, an area with unmet clinical need. We searched PubMed, Embase, Institute of Electrical and Electronics Engineers Xplore, and Web of Science from January 2015 to December 2024. Two reviewers screened records, extracted data, and used a modified appraisal emphasizing explainability, performance, reproducibility, and ethics. From 2847 records, 89 studies met incl

Clinical Trials of Stem Cell Therapy in Japan: The Decade of Progress under the National Program.

Stem cell therapy is a current world-wide topic in medical science. Various therapies have been approved based on their effectiveness and put into practical use. In Japan, research and development-related stem cell therapy, generally referred to as regenerative medicine, has been led by the government. The national scheme started in 2002, and support for the transition to clinical trials has been accelerating since 2011. Of the initial 18 projects that were accepted in the budget for preclinical research, 15 projects have begun clinical trials so far. These include the transplantation of retin