Antibody/siRNA Nanocarriers Against Wnt Signaling Suppress Oncogenic and Stem-Like Behavior in Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) is infamous for its aggressive phenotype and poorer prognosis when compared to other breast cancer subtypes. One factor contributing to this poor prognosis is that TNBC lacks expression of the receptors that available hormonal or molecular-oriented therapies attack. New treatments that exploit biological targets specific to TNBC are desperately needed to improve patient outcomes.

Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial.

Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes.

Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone).

Investigating proteogenomic divergence in patient-derived xenograft models of ovarian cancer.

Within ovarian cancer research, patient-derived xenograft (PDX) models recapitulate histologic features and genomic aberrations found in original tumors. However, conflicting data from published studies have demonstrated significant transcriptional differences between PDXs and original tumors, challenging the fidelity of these models. We employed a quantitative mass spectrometry-based proteomic approach coupled with generation of patient-specific databases using RNA-seq data to investigate the proteogenomic landscape of serially-passaged PDX models established from two patients with distinct subtypes of ovarian cancer.

Phase 2 Open-Label Study of Sacituzumab Govitecan as Second-Line Therapy in Patients With Extensive-Stage Small Cell Lung Cancer: Results From TROPiCS-03.

Introduction: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC).

Methods: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study in solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one prior line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle.

Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells.

CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226.

NUFIP1 integrates amino acid sensing and DNA damage response to maintain the intestinal homeostasis.

Nutrient availability strongly affects intestinal homeostasis. Here, we report that low-protein (LP) diets decrease amino acids levels, impair the DNA damage response (DDR), cause DNA damage and exacerbate inflammation in intestinal tissues of male mice with inflammatory bowel disease (IBD). Intriguingly, loss of nuclear fragile X mental retardation-interacting protein 1 (NUFIP1) contributes to the amino acid deficiency-induced impairment of the DDR in vivo and in vitro and induces necroptosis-related spontaneous enteritis.

Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial.

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.

Comprehensive characterization of the transcriptional landscape in Alzheimer's disease (AD) brains.

Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts, encompassing 33,321 long ncRNAs, 92,897 enhancer RNAs, 53,763 alternative polyadenylation events, and 900,221 A-to-I RNA editing events.

Design and Synthesis of Triazine-Based Hydrogel for Combined Targeted Doxorubicin Delivery and PI3K Inhibition.

Melanoma, an aggressive skin cancer originating from melanocytes, presents substantial challenges due to its high metastatic potential and resistance to conventional therapies. Hydrogels, 3D networks of hydrophilic polymers with high water-retention capacities, offer significant promise for controlled drug delivery applications. In this study, we report the synthesis and characterization of hydrogelators based on the triazine molecular scaffold, which self-assemble into fibrous networks conducive to hydrogel formation.

Viral oncogene EBNALP regulates YY1 DNA binding and alters host 3D genome organization.

The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNALP) is essential for the immortalization of naive B lymphocytes (NBLs). However, the mechanisms remain elusive. To understand EBNALP's role in B-cell transformation, we compare NBLs infected with wild-type EBV and an EBNALP-null mutant EBV using multi-omics techniques.

The dynamic oral-gastric microbial axis connects oral and gastric health: current evidence and disputes.

Emerging evidence indicates that oral microbes are closely related to gastric microbes and gastric lesions, including gastric atrophy, intestinal metaplasia and gastric cancer (GC). Helicobacter pylori is a key pathogen involved in GC. However, the increasing prevalence of H.

Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product.

Circulating Tumor Cells (CTCs) in blood encompass DNA, RNA, and protein biomarkers, but clinical utility is limited by their rarity. To enable tumor epitope-agnostic interrogation of large blood volumes, we developed a high-throughput microfluidic device, depleting hematopoietic cells through high-flow channels and force-amplifying magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.

Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis.

Background: Circadian rhythms in the immune system and anti-tumor responses are underexplored in cancer immunotherapy. Despite the success of immune checkpoint inhibitors (ICIs) in treating advanced biliary tract cancers (BTCs), not all patients benefit. This study examined whether the timing of ICI administration affects outcomes in advanced BTC patients.

Artemisinin Suppressed Melanoma Recurrence and Metastasis after Radical Surgery through the KIT/PI3K/AKT Pathway.

Cancer radical surgery is the primary treatment for melanoma, but almost all malignant melanoma patients get recurrence and metastasis after surgery and are eventually dead. This clinical dilemma appeals to better drugs for post-surgery therapy. Artemisinin is a safe and effective antimalarial drug used in the clinic for decades.

Durable and deep response to CVD chemotherapy in SDHB-mutated metastatic paraganglioma: case report.

Introduction: Succinate dehydrogenase subunit B (SDHB)-mutated paragangliomas (PGLs) are rare neuroendocrine tumors characterized by increased malignancy, readily metastasizing, and poorer prognosis. Here we report a case of SDHB-mutated metastatic PGL, wherein the patient showed significant tumor shrinkage and complete symptom remission following chemotherapy. We aim to contribute additional evidence to the existing knowledge associated with SDHB-mutated PGLs.

Conference 2024: Building an innovative scientific research ecosystem for microbiome and One Health.

The Conference 2024 provides a platform to promote the development of an innovative scientific research ecosystem for microbiome and One Health. The four key components - Technology, Research (Biology), Academic journals, and Social media - form a synergistic ecosystem. Advanced technologies drive biological research, which generates novel insights that are disseminated through academic journals.

Efficacy and safety of S-1 plus oxaliplatin combined with apatinib and camrelizumab as neoadjuvant therapy for patients with locally advanced gastric or gastroesophageal junction adenocarcinoma: a protocol for a single-arm phase II trial.

Gastric cancer, as the fifth most diagnosed malignancy and the fourth leading cause of cancer-related death globally, remains a significant health concern. The potential effect of the programmed death-1 (PD-1) inhibitor, when used alongside chemotherapy and antiangiogenic agents in neoadjuvant therapy for gastric cancer, has yet to be explored in the published literature. This study aims to evaluate the efficacy and safety of the S-1 plus oxaliplatin (SOX) regimen when combined with apatinib and camrelizumab (SOXAC) as neoadjuvant therapy for patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

Using artificial intelligence and statistics for managing peritoneal metastases from gastrointestinal cancers.

Objective: The primary objective of this study is to investigate various applications of artificial intelligence (AI) and statistical methodologies for analyzing and managing peritoneal metastases (PM) caused by gastrointestinal cancers.

Methods: Relevant keywords and search criteria were comprehensively researched on PubMed and Google Scholar to identify articles and reviews related to the topic. The AI approaches considered were conventional machine learning (ML) and deep learning (DL) models, and the relevant statistical approaches included biostatistics and logistic models.

Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC), characterized by its lack of traditional hormone receptors and HER2, presents a significant challenge in oncology due to its poor response to conventional therapies. Autophagy is an important process for maintaining cellular homeostasis, and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors. In contrast to targeting protein activity, intervention with protein-protein interaction (PPI) can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.

From the microspheres to scaffolds: advances in polymer microsphere scaffolds for bone regeneration applications.

The treatment and repair of bone tissue damage and loss due to infection, tumours, and trauma are major challenges in clinical practice. Artificial bone scaffolds offer a safer, simpler, and more feasible alternative to bone transplantation, serving to fill bone defects and promote bone tissue regeneration. Ideally, these scaffolds should possess osteoconductive, osteoinductive, and osseointegrative properties.

Thermosensitive hydrogel delivery of BCG lysates and tumor antigens: A novel strategy for melanoma immunoprevention and therapeutics.

Melanoma, recognized as one of the most aggressive forms of skin cancer, continues to show a steady rise in global incidence. While Bacillus Calmette-Guérin (BCG) has been identified as a potential intralesional therapy for melanoma, its therapeutic efficacy remains suboptimal. This study introduces a novel thermosensitive hydrogel formulated with BCG lysates and either OVA peptide or tumor cell lysates (PPP-BCG-OVA/TL).