Photocrosslinking of hyaluronic acid-based hydrogels through biotissue barriers.

Photocrosslinkable hydrogels based on hyaluronic acid are promising biomaterials high in demand in tissue engineering. Typically, hydrogels are photocured under the action of UV or blue light strongly absorbed by biotissues, which limits prototyping under living organism conditions. To overcome this limitation, we propose the derivatives of well-known photosensitizers, namely chlorin , chlorin and phthalocyanine, as those for radical polymerization in the transparency window of biotissues.

Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Methods: In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries.

Anticancer Plant Secondary Metabolites Evicting Linker Histone H1.2 from Chromatin Activate Type I Interferon Signaling.

Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the chromatin-bound linker histones H1.2 and/or H1.4.

Synthesis of New Promising BNCT Agents Based on Conjugates of -Dodecaborate Anion and Aliphatic Diamino Acids.

In this work, a series of boronated amidines based on the -dodecaborate anion and amino acids containing an amino group in the side chain of the general formula [BHNHC(NH(CH)CH(NH)COOH)CH], where n = 2, 3, 4, were synthesized. These derivatives contain conserved α-amino and α-carboxyl groups recognized by the binding centers of the large neutral amino acid transporter (LAT) system, which serves as a target for the clinically applied BNCT agent para-boronophenylalanine (BPA). The paper describes several approaches to synthesizing the target compounds, their acute toxicity studies, and tumor uptake studies in vivo in two tumor models.

N-Glycoside of Indolo[2,3-]pyrrolo[3,4-]carbazole LCS1269 Exerts Anti-Glioblastoma Effects by G2 Cell Cycle Arrest and CDK1 Activity Modulation: Molecular Docking Studies, Biological Investigations, and ADMET Prediction.

Indolo[2,3-]pyrrolo[3,4-]carbazole scaffold is successfully used as an efficient structural motif for the design and development of different antitumor agents. In this study, we investigated the anti-glioblastoma therapeutic potential of glycosylated indolocarbazole analog LCS1269 utilizing in vitro, in vivo, and in silico approaches. Cell viability was estimated by an MTT assay.

Divergent Contribution of Cytoplasmic Actins to Nuclear Structure of Lung Cancer Cells.

A growing body of evidence suggests that actin plays a role in nuclear architecture, genome organisation, and regulation. Our study of human lung adenocarcinoma cells demonstrates that the equilibrium between actin isoforms affects the composition of the nuclear lamina, which in turn influences nuclear stiffness and cellular behaviour. The downregulation of β-actin resulted in an increase in nuclear area, accompanied by a decrease in A-type lamins and an enhancement in lamin B2.

Molecular Subgroups of HRD Positive Ovarian Cancer and Their Prognostic Significance.

Homologous recombination repair deficiency (HRD) is involved in the development of high-grade serous ovarian carcinoma (HGSOC) and its elevated sensitivity to platinum-based chemotherapy. To investigate the heterogeneity of the HRD-positive HGSOC we evaluated the HRD status, including BRCA mutations, genomic scar score, and methylation status of genes in 352 HGSOC specimens. We then divided the HRD-positive cohort into three molecular subgroups, the BRCA mutation cohort (BRCA+), BRCA1 methylation cohort (Meth+), and the rest of the HRD+ cohort (HRD+BRCA-Meth-), and evaluated their first-line chemotherapy response, benefit from olaparib, and progression-free survival (PFS).

Impact of Race on the Outcomes of Retinoblastoma Treated With Primary Enucleation: A Global Study of 1426 Patients.

Background: To evaluate the clinical presentation, pathological features and outcomes of retinoblastoma based on the race of origin in a global cohort of patients.

Methods: Retrospective collaborative study of 1426 patients who underwent primary enucleation for retinoblastoma.

Results: Patients were grouped into Caucasians (n = 231, 16%), Asians (n = 841, 59%), Hispanics (n = 226, 16%), Arabs (n = 96, 7%) and Others (Africans, African Americans, Indigenous Australians; n = 32, 2%) cohorts.

An update on access to novel treatment for metastatic melanoma in Europe - A 2024 survey of the European melanoma registry and the European association of dermato-oncology.

Advances in cancer treatments have significantly improved their effectiveness, yet access to first-line therapies remains limited. A 2017 survey revealed that over 25 % of metastatic melanoma patients in Europe lacked access to recommended therapies. To address this, the European Association of Dermato-Oncology and the European Melanoma Registry conducted a follow-up study on the registration and reimbursement of first-line treatments.

Artificial intelligence in surgery: evolution, trends, and future directions.

Artificial intelligence (AI) is significantly transforming surgery by enhancing precision, decision-making, and patient outcomes. This bibliometric analysis examines AI's impact on surgery, highlighting research trends, key contributors, and evolving themes from 1998 to 2024. Utilizing data from the Web of Science Core Collection and analyzed through the Bibliometrix tool, the study reviews publication trends, author impact, institutional contributions, country-specific research activities, and keyword frequency.

Decoding Chemotherapy Resistance of Undifferentiated Pleomorphic Sarcoma at the Single Cell Resolution: A Case Report.

Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant mesenchymal tumor that ranks as one of the most common types of soft tissue sarcoma. Even though chemotherapy increases the 5-year survival rate in UPS, high tumor heterogeneity frequently leads to chemotherapy resistance and consequently to recurrences. In this study, we characterized the cell composition and the transcriptional profile of UPS with resistance to chemotherapy at the single cell resolution.

Could Be a Promising Marker for Preoperative Diagnosis of High-Grade Papillary Thyroid Carcinoma?

Background/objectives: A modern classification distinguishes between two nosological entities posing an intermediate risk between differentiated and anaplastic carcinoma: poorly differentiated thyroid carcinoma and differentiated high-grade thyroid carcinoma. There are currently few studies searching for the preoperative molecular genetic markers of high-grade papillary thyroid carcinoma (PTC HG), primarily because of a recent WHO reclassification and singling out of a separate entity: high-grade follicular cell-derived nonanaplastic thyroid carcinoma. Therefore, this work was aimed at identifying PTC HG-specific microRNAs and mRNAs that reliably distinguish them from differentiated papillary thyroid carcinoma in preoperative cytology specimens (fine-needle aspiration biopsies).

Durvalumab Versus Chemotherapy as First-line Treatment for Metastatic NSCLC With Tumor PD-L1 Expression of 25% or Higher: Results From the Randomized Phase 3 PEARL Study.

Introduction: PEARL (NCT03003962) is an open-label, phase 3 study comparing first-line durvalumab monotherapy with chemotherapy in patients with metastatic NSCLC (mNSCLC [EGFR/ALK wild type]) with programmed cell death ligand 1 (PD-L1) tumor cell (TC) membrane expression status of 25% or higher. We report the final analysis of PEARL.

Methods: Adults (N = 669) with previously untreated stage IV mNSCLC were randomized (1:1) to durvalumab 20 mg/kg every four weeks or chemotherapy every three weeks for four to six cycles.

Ten Hypermethylated lncRNA Genes Are Specifically Involved in the Initiation, Progression, and Lymphatic and Peritoneal Metastasis of Epithelial Ovarian Cancer.

Our work aimed to evaluate and differentiate the role of ten lncRNA genes (, , , , , , , , , and ) in the development and progression of epithelial ovarian cancer (EOC). A representative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation levels of all ten lncRNA genes in tumors compared to normal tissues ( < 0.

1,3-Dipolar Cycloaddition of Nitrile Oxides and Nitrilimines to (-)-β-Caryophyllene: Stereoselective Synthesis of Polycyclic Derivatives and Their Biological Testing.

The cycloaddition of nitrile oxides and nitrilimines to one or both of the C=C double bonds of caryophyllene is described. The possibility of introducing five-membered fused and spiro-linked heterocycles into the structure of sesquiterpenes by the 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrilimines to caryophyllene was demonstrated. As a result of these reactions, pharmacophore fragments of isoxazoline and pyrazoline are introduced into the structure of caryophyllene, which leads to an increase in the conformational rigidity of the molecule.

Photochemical Metal-Free synthesis and biological Assessment of isocryptolepine analogues targeting estrogen receptor Alpha in breast cancer cells.

The aim of this study was to develop a new series of isocryptolepines and evaluate their antiproliferative and antiestrogenic activities on cancer cells. A series of isocryptolepine derivatives were synthesized using developed one-pot photochemical, metal-free protocol, employing readily available 2-arylindoles as starting compounds. The resulting isocryptolepines demonstrated (sub)micromolar inhibitory activity against selected breast cancer cell lines.

Revealing molecular mechanisms of early-onset tongue cancer by spatial transcriptomics.

Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear.

Synthesis of 13β- and 13α-epimers of 3-hydroxy-17-hydroxymethylestra-1,3,5(10)-triene and considerations on their hormonal and antiproliferative potency.

Starting from 3-methoxyestra-1,3,5(10),16-tetraene-17-carbaldehydes of natural (13β) and epimeric (13α) series, a series of isomeric 3-hydroxy-17-hydroxymethylestra-1,3,5(10)-trienes, including those containing 16α,17α-annulated cyclopropane and cyclohexane ring D', were prepared using the Corey-Chaykovsky and Diels-Alder reactions followed by reduction-demethylation with diisobutylaluminum hydride and hydrogenation. Target compounds showed antiproliferative effects on MCF-7 breast cancer cells to varying degrees superior to that on MCF-10A cells, in low micromolar concentrations. The ERα-mediated luciferase reporter gene assay demonstrated that obtained steroids without an additional carbocycle or with a cyclopropane 16α,17α-annulated carbocycle are effective ERα activators.

Characterization of Extracellular Vesicles by Sulfophosphovanillin Colorimetric Assay and Raman Spectroscopy.

Background: Detailed characterization of extracellular vesicles (EVs) is crucial for their application in medical diagnostics. However, the complexity of their chemical composition and the heterogeneity of EV populations make their characterization challenging. Here we describe two analytical procedures that can help overcome this challenge.

Assessment of a Structurally Modified Alternanthera Mosaic Plant Virus as a Delivery System for Sarcoma Cells.

The virions of plant viruses and their structurally modified particles (SP) represent valuable platforms for recombinant vaccine epitopes and antitumor agents. The possibility of modifying their surface with biological compounds makes them a tool for developing medical biotechnology applications. Here, we applied a new type of SP derived from virions and virus-like particles (VLP) of Alternanthera mosaic virus (AltMV) and well-studied SP from Tobacco mosaic virus (TMV).