Deep hematologic response to RD treatment in patients with multiple myeloma is associated with overexpression of IL-17R in CD138+ plasma cells

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Окт. 9, 2024

Lenalidomide (LEN) is widely used immunomodulatory drug (IMiD). Nonetheless, despite its efficacy, over time patients become resistant to LEN and relapse. Due high clinical relevance, resistance in MM being thoroughly investigated. However, less known about predictors of good response LEN-based treatment. The aim this study was identify molecular pathways associated with long LEN. included newly diagnosed (NDMM) treated first-line dexamethasone (RD) who achieved least very partial remission (VGPR). RNA isolated from cells new-generation sequencing performed. Obtained results were validated qRT-PCR. A global increase gene expression found the RD group compared NDMM, suggesting involvement epigenetic mechanisms. Moreover, upregulation genes controlling interaction within niche detected. Next, immune upregulated. In particular, encoding IL-17 receptor overexpressed which a novel finding. This should be emphasized because IL-17-related signaling can potentially targeted, providing rationale for future research. Establishing background long-lasting profound may improve chemotherapy regimens facilitate development adjuvant therapies enhance anti-MM activity.

Язык: Английский

---

Identification of tumor heterogeneity associated with KRAS/TP53 co-mutation status in lung adenocarcinoma based on single-cell RNA sequencing

American Journal of Cancer Research, Год журнала: 2024, Номер 14(2), С. 655 - 678

Опубликована: Янв. 1, 2024

Lung cancer stands as the predominant cause of cancer-related mortality globally. adenocarcinoma (LUAD), being most prevalent subtype, garners extensive attention due to its notable heterogeneity, which significantly influences tumor development and treatment approaches. This research leverages single-cell RNA sequencing (scRNA-seq) datasets delve into impact KRAS/TP53 co-mutation status on LUAD. Moreover, utilizing TCGA-LUAD dataset, we formulated a novel predictive risk model, comprising seven prognostic genes, through LASSO regression, subjected it both internal external validation sets. The study underscores profound co-mutational microenvironment (TME) Crucially, markedly extent B cell infiltration various immune-related pathways within TME. newly developed model exhibited robust performance across sets, establishing itself viable independent factor. Additionally, in vitro experiments indicate that MELTF PLEK2 can modulate invasion proliferation human non-small lung cells. In conclusion, elucidated co-mutations may TME patient prognosis by orchestrating cells affiliated pathways. Furthermore, spotlight not only function indicators for LUAD, but also lay foundation exploration innovative therapeutic

Язык: Английский

---

Circular RNA circHIPK2 inhibits colon cancer cells through miR-373-3p/RGMA axis

Cancer Letters, Год журнала: 2024, Номер 593, С. 216957 - 216957

Опубликована: Май 16, 2024

Язык: Английский

---

PLEK2 activates the PI3K/AKT signaling pathway to drive lung adenocarcinoma progression by upregulating SPC25

Cell Biology International, Год журнала: 2024, Номер 48(9), С. 1285 - 1300

Опубликована: Июнь 18, 2024

Abstract Lung adenocarcinoma (LUAD) is the most common subtype of NSCLC, characterized by poor prognosis and frequently diagnosed at advanced. While previous studies have demonstrated pleckstrin‐2 (PLEK2) as aberrantly expressed implicated in tumorigenesis across various tumor types, including LUAD, molecular mechanisms underlying PLEK2‐mediated LUAD progression remain incompletely understood. In this study, we obtained data from The Cancer Genome Atlas (TCGA) database to assess PLEK2 expression a finding further confirmed through analysis human tissue specimens. PLEK2‐silenced cellular models were subsequently constructed examine functional role both vitro vivo. Our results showed elevated correlating with patients' prognosis. knockdown led significant suppression cell proliferation migration, accompanied enhanced apoptosis. Moreover, growth mice injected PLEK2‐silencing cells was impaired. Gene profiling Co‐IP assays suggested direct interaction between SPC25, downregulation SPC25 similarly impairing migration. Additionally, revealed phosphoinositide 3‐kinase (PI3K)/AKT signaling activation requisite for PLEK2‐induced malignant phenotypes LUAD. Collectively, our findings underscore PLEK2's oncogenic potential suggesting its utility prognostic indicator therapeutic target management.

Язык: Английский

---

OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Март 8, 2024

Abstract Background Intestinal metaplasia (IM) is classified into complete intestinal (CIM) and incomplete (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring critical need for early screening measures. In addition complexities associated diagnosis, exact mechanisms driving progression cancer in patients remain poorly understood. OLFM4 overexpressed several types tumors, including colorectal, gastric, pancreatic, ovarian cancers, its expression has been tumor progression. Methods this study, we used pathological sections from two clinical centers, biopsies IM tissues, precancerous lesions (PLGC) cell models, animal organoids explore role IIM. Results Our results show that highly increased IIM, superior diagnostic accuracy when compared CDX2 MUC2. OLFM4, along MYH9, was PLGC models. Furthermore, combination Myosin heavy chain 9 (MYH9), accelerated ubiquitination GSK3β resulted β-catenin levels through Wnt signaling pathway, promoting proliferation invasion abilities cells. Conclusions represents a novel biomarker could be utilized as important auxiliary means delimit key population screening. Finally, our study identifies pathways involved IM.

Язык: Английский

---

Engineering and targeting potential of CAR NK cells in colorectal cancer

Chinese Medical Journal, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

Abstract Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promise, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, specific mechanisms underlying NK cell trafficking their interplay within complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into design engineering of targets in CRC, success overcoming resistance an emphasis on potential for clinical trials.

Язык: Английский

---

Current biological implications and clinical relevance of metastatic circulating tumor cells

Clinical and Experimental Medicine, Год журнала: 2024, Номер 25(1)

Опубликована: Ноя. 15, 2024

Metastatic disease and cancer recurrence are the primary causes of cancer-related deaths. Circulating tumor cells (CTCs) disseminated (DTCs) driving forces behind spread cells. The emergence development liquid biopsy using rare CTCs as a minimally invasive strategy for early-stage detection improved management is promising advancement in recent years. However, before blood sample analysis clinical translation, precise isolation from patients' based on their biophysical properties, followed by molecular identification single-cell multi-omics technologies necessary to understand heterogeneity provide effective diagnosis monitoring progression. Additionally, understanding origin, morphological variation, interaction between metastatic niche, well regulatory immune cells, will offer new insights into CTC-based advanced targeting future trials.

Язык: Английский

---

Unveiling the role of Pleckstrin-2 in tumor progression and immune modulation: insights from a comprehensive pan-cancer analysis with focus on lung cancer

Molecular Biomedicine, Год журнала: 2024, Номер 5(1)

Опубликована: Ноя. 15, 2024

Abstract Cancer remains a leading cause of mortality globally, highlighting the need for novel biomarkers to enhance prognosis and therapeutic strategies. Pleckstrin-2 (PLEK2), member pleckstrin family, has been implicated in processes critical tumor progression, but its role across cancers underexplored. This study systematically examined expression patterns, prognostic relevance, functional impact PLEK2 multiple cancer types. Using data from The Genome Atlas (TCGA), Genotype Tissue Expression Project (GTEx), Human Protein Atlas, we analyzed both cancerous normal tissues, revealing significant overexpression various at mRNA protein levels. Single-cell RNA sequencing further indicated predominant cells macrophages within microenvironment. Survival analysis demonstrated that elevated correlated with poor specific cancers, though varied Functional assays showed knockdown inhibited proliferation migration human cell lines. In vivo studies using Lewis lung carcinoma (LLC) model confirmed suppressed growth enhanced efficacy PD-1 immunotherapy. Mechanistically, was associated reduced AKT pathway activation, diminished tumor-associated macrophage infiltration, increased CD8 T presence. Compounds like Navitoclax were also identified as potential inhibitors. conclusion, played multifaceted progression immune response modulation. Targeting might suppress overcome immunotherapy resistance, offering promising biomarker target improve treatment outcomes.

Язык: Английский

---

Polo-like kinase 4 accelerates glioma malignant progression and vasculogenic mimicry by phosphorylating EphA2

Cancer Letters, Год журнала: 2024, Номер unknown, С. 217397 - 217397

Опубликована: Дек. 1, 2024

Язык: Английский

---