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Proteomic alterations in ovarian cancer-Predicting residual disease status using artificial intelligence and SHAP-based biomarker interpretation.

IntroductionHigh-grade serous ovarian cancer (HGSOC) is the most aggressive and prevalent subtype of ovarian Treatment outcomes are significantly influenced by residual disease status following neoadjuvant chemotherapy (NACT). Predicting residual disease before surgery can improve patient stratification and personalized treatment strategies.MethodsThis study analyzed pre-NACT proteomic data from 20 HGSOC patients treated with NACT. Patients were categorized into two groups based on surgical outcomes: no residual disease (R0, n = 14) and suboptimal residual disease (R1, n = 6). From an initial

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… In particular, BRCA1/2 mutations and homologous recombination repair deficiency (HRD) have been shown to significantly influence the chemotherapy response. …

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecu

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

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… The Cancer Genome Atlas findings on OC showed that there are few recurrent mutated genes, with four transcript subtypes and the presence of extensive defects homologous recombination with mutual exclusivity [ 82 ]. …

A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors.

The present coronavirus disease 2019 (COVID-19) pandemic scenario has posed a difficulty for cancer treatment. Even under ideal conditions, malignancies like small cell lung cancer (SCLC) are challenging to treat because of their fast development and early metastases. The treatment of these patients must not be jeopardized, and they must be protected as much as possible from the continuous spread of the COVID-19 infection. Initially identified in December 2019 in Wuhan, China, the contagious coronavirus illness 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (S

Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease.

Chimeric antigen receptor (CAR)-T cell therapies represent a promising therapeutic approach for refractory autoimmune diseases. Although autologous CAR-T cells have achieved success thus far, they require expensive, individualised manufacturing, limiting their commercialisation potential. Allogeneic alternatives could overcome these scalability barriers, providing 'off-the-shelf' treatments, although they raise the issues of graft-vs-host reactions and host-mediated rejection. To mitigate such risks, gene-edited αβ T cells or non-alloreactive host cells (e.g., NK cells, γδ T cells) may be used

Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).

Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑

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… This mechanism enhances homologous recombination-mediated repair and reduces radiation lethality in esophageal squamous carcinoma cells ( 294 ). Vav guanine nucleotide exchange factor 2 (VAV2) is another candidate target. …

Targeted CD7 CAR T-cells for treatment of T-Lymphocyte leukemia and lymphoma and acute myeloid leukemia: recent advances.

The high expression of CD7 targets in T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoma has attracted considerable attention from researchers. However, because CD7 chimeric antigen receptor (CAR) T-cells undergo fratricide, CD7 CAR T-cells develop an exhaustion phenotype that impairs the effect of CAR T-cells. There have been significant breakthroughs in CD7-targeted CAR T-cell therapy in the past few years. The advent of gene editing, protein blockers, and other approaches has effectively overcome the adverse effects of conventional methods of CD7 CAR T-cells. This review, in conjunc

Euchromatic Histone Lysine Methyltransferase 2 Inhibition Enhances Carfilzomib Sensitivity and Overcomes Drug Resistance in Multiple Myeloma Cell Lines.

Proteasome inhibitors (PIs) are extensively used for the therapy of multiple myeloma. However, patients continuously relapse or are intrinsically resistant to this class of drugs. In addition, adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise. Here, to identify compounds that can increase the efficacy of PIs, we performed a functional screening using a library of small-molecule inhibitors covering key signaling pathways. Among the best synthetic lethal interactions, the euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor UNC0642 displayed a coope

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… The increased 53BP1 level following treatments suggested a prevalence of non-homologous end joining (NHEJ) repair over homologous recombination repair (HRR), which could lead to error accumulation and apoptotic cell death ( Figure 6 c). …

Abemaciclib, A Selective CDK4/6 Inhibitor, Restricts the Growth of Pediatric Ependymomas.

Pediatric ependymomas are a type of malignant brain tumor that occurs in children. The overall 10-year survival rate has been reported as being 45-75%. Maximal safe surgical resection combined with adjuvant chemoradiation therapy is associated with the highest overall and progression-free survival rates. Despite aggressive treatment, one-third of ependymomas exhibit recurrence within 2 years of initial treatment. Therefore, this study aimed to find new agents to overcome chemoresistance and defer radiotherapy treatment since, in addition, radiation exposure may cause long-term side effects in

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… Our previous study demonstrated that knockdown of cyclin D1 expression resulted in lower RAD51 and BRCA2 expression and suppressed the ability of cells to undergo homologous recombination [ 2 ]. …

Development, efficacy and side effects of antibody‑drug conjugates for cancer therapy (Review).

Antibody-drug conjugates (ADCs) are anticancer drugs that combine cytotoxic small-molecule drugs (payloads) with monoclonal antibodies through a chemical linker and that transfer toxic payloads to tumor cells expressing target antigens. All ADCs are based on human IgG. In 2009, the Food and Drug Administration (FDA) approved gemtuzumab ozogamicin as the initial first-generation ADC. Since then, at least 100 ADC-related projects have been initiated, and 14 ADCs are currently being tested in clinical trials. The limited success of gemtuzumab ozogamicin has led to the development of optimization

Induction of Pro-Apoptotic Endoplasmic Reticulum Stress in Multiple Myeloma Cells by NEO214, Perillyl Alcohol Conjugated to Rolipram.

Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of

Семья " Interleukin-17 " в области здравоохранения и иммунных заболеваний: от происхождения до клинических последствий.

Семья интерлейкин-17 является ключевой группой цитокинов и демонстрирует широкий спектр биологических функций, включая регулирование подстрекательского каскада в различных аутоиммунных и подстрекательских болезнях, таких, как множественный склероз, оптический спектр нейромилита, миастения гравис, синдром Гильен-Барре, острый распределенный энцфаломиэлит, диабет, воспалительные кожные заболевания, суставное воспаление и рак. Хотя функция семьи интерлейкин-17 привлекает все большее внимание к исследованиям на протяжении многих лет, выражение, функции и механизмы регулирования различных членов се

FDA-Approved Small Molecule Compounds as Drugs for Solid Cancers from Early 2011 to the End of 2021.

Solid cancers are the most common types of cancers diagnosed globally and comprise a large number of deaths each year. The main challenge currently in drug development for tumors raised from solid organs is to find more selective compounds, which exploit specific molecular targets. In this work, the small molecule drugs registered by the Food and Drug Administration (FDA) for solid cancers treatment between 2011 and 2022 were identified and analyzed by investigating a type of therapy they are used for, as well as their structures and mechanisms of action. On average, 4 new small molecule agent

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… The cancer cells use PARP-mediated DNA repair for homologous recombination and survival, thereby being sensitive to PARPs inhibition [ 173 ]. In the last decade, olaparib , rucaparib , niraparib and talazoparib have been FDA-approved inhibitors of PARPs catalytic activity. …

Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.

Gene editing is a groundbreaking therapeutic approach that can potentially treat a broad spectrum of genetic and acquired diseases. This review highlights recent clinical trials employing advanced gene editing technologies such as CRISPR-Cas9, zinc-finger nucleases (ZFNs), and base editors across multiple disease areas including metabolic disorders, autoimmune diseases, muscular dystrophies, and inherited eye disorders. Central to the success of these therapies is the development of efficient and safe delivery systems, including lipid nanoparticles (LNPs), viral vectors (adenoviral and lentivi

Understanding Autoimmunity: Mechanisms, Predisposing Factors, and Cytokine Therapies.

Autoimmunity refers to an organism's immune response against its own healthy cells, tissues, or components, potentially leading to irreversible damage to vital organs. Central and peripheral tolerance mechanisms play crucial roles in preventing autoimmunity by eliminating self-reactive T and B cells. The disruption of immunological tolerance, characterized by the failure of these mechanisms, results in the aberrant activation of autoreactive lymphocytes that target self-tissues, culminating in the pathogenesis of autoimmune disorders. Genetic predispositions, environmental exposures, and immun

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

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… Rad51 performs an important function in homologous strand exchange, which is a key step in DNA repair through homologous recombination (HR). Results of this study confirmed that the silencing of Rad51 improves the radiation-induced death of tumor cells ( 145 ). …

Half a century of healing: celebrating the 50th anniversary of EBMT.

EBMT is a non-profit organization with a clear mission: "to save the lives of patients with blood cancers and other life-threatening diseases by advancing the fields of blood and marrow transplantation and cell therapy worldwide through science, education and advocacy". In 1974, EBMT was established by European physicians in St. Moritz to share bone marrow transplantation (BMT) experiences and foster collaboration. Founding members included Jon Van Rood, Bruno Speck, and Eliane Gluckman. By 1989, the group expanded significantly, emphasizing mutual trust and collaboration. EBMT played a crucia

Induction and Regulation of the Immunoproteasome Subunit β5i (PSMB8) in Laryngeal and Hypopharyngeal Carcinoma Cells.

BACKGROUND The ubiquitin-proteasome pathway (UPP) is closely associated with the occurrence and progression of cancer, and the 5i immunoproteasome subunit is an important antitumor target in UPP. This study aimed to characterize the regulation of the immunoproteasome subunit ß5i (PSMB8) in JHU-011 laryngeal carcinoma cells and FaDu hypopharyngeal carcinoma cells to explore a new target for the treatment of laryngeal and hypopharyngeal carcinomas. MATERIAL AND METHODS JHU-011 and FaDu cells were used as effector cells in this study. By means of ⁶⁰Co γ-irradiation, the construction of stable cel

Update on the Treatment of Metastatic Urothelial Carcinoma.

Platinum-based combination chemotherapy has been the standard of care in the first-line treatment of metastatic urothelial carcinoma (mUC). Treatment of metastatic disease following progression on platinum-based regimens has evolved significantly in the last few years. Clinical trials are currently ongoing to determine how best to use and sequence these treatments. In this minireview, we will review current first-line treatment options in both cisplatin fit and cisplatin unfit patients and advances in first- and second-line treatments including chemotherapy and immunotherapy. This review repor

Dietary Polyphenols and Their Biological Significance

Dietary polyphenols represent a wide variety of compounds that occur in fruits, vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They are mostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins and phenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis, anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascular protection, improvement of the endothelial function, as well as inhibition of angiogenesis and cell proliferation activity. Most of these biological actions have bee