Androgen deprivation therapy (ADT) has been associated with increased cardiovascular and renal risks in prostate cancer patients. We performed a systematic review and meta-analysis of the currently available evidence to evaluate the rates of acute kidney injury (AKI) in prostate cancer patients under ADT.

PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to October 2024. Eligible observational studies comparing prostate cancer patients receiving ADT with those not receiving ADT were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using I², τ², and 95% prediction intervals. Risk of bias and certainty of evidence were evaluated using the Newcastle-Ottawa Scale and GRADE framework, respectively. Statistical analyses were performed using R software version 4.3.1, and the study was reported according to PRISMA and MOOSE recommendations.

Four studies involving 72,980 patients were included. ADT was significantly associated with AKI occurrence when compared with the non-ADT control group (OR 1.34; 95% CI 1.29-1.40; p < 0.001; I2 = 68%). In a subgroup analysis, GnRH agonists demonstrated positive association with AKI risk (OR 1.49; 95% CI 1.02-2.17; p = 0.038; I2 83.1%). In contrast, orchiectomy was not associated with AKI (OR 1.1; 95% CI 0.85-1.42; p = 0.488; I2 = 0%). GnRH agonist ADT, compared to other ADT modalities, demonstrated negative association with AKI (OR 0.77; 95% CI 0.61-0.98; p = 0.035; I2 = 0%). The analysis of orchiectomy against GnRH agonist therapy suggests lower AKI rate in orchiectomized patients (OR 0.77; 95% CI 0.66-0.91; p = 0.001; I2 = 0%).

ADT was associated with higher odds of AKI among patients with prostate cancer. The association was particularly evident among patients receiving GnRH agonist-based therapy. However, the findings should be interpreted in light of the observational nature of the available evidence and the methodological limitations related to the synthesis of effect estimates reported using different statistical approaches.

Pleomorphism in cells encompasses a variety of morphological features, such as heterogeneity in the size and shape of cells and nuclei, irregularity of the nuclear membrane, hyperchromasia, and peculiarities of cell organelles. Pleomorphism in mammalian cells is associated with genetically unstable neoplasms and is frequently accompanied by high rates of proliferation and low differentiation status. Among soft tissue sarcomas, a group of tumors characterized by the pleomorphic phenotype can be distinguished. Pleomorphic soft tissue sarcomas are a rare, understudied group of soft tissue sarcomas with aggressive behavior, low survival rates, and high resistance to standard chemotherapy treatment. Knowledge of the mechanisms behind the pleomorphic features, common genetic and epigenetic alterations, and their association with aggressive tumorigenesis is essential for advancing patient care for this group of sarcomas. In this narrative review, we consolidate existing evidence concerning clinical features of pleomorphic sarcomas, their possible histogenesis, the common drivers and transcriptional networks, and the potentially available approaches for treatment.

Chemotherapy-induced nausea and vomiting (CINV) remain difficult to control after discharge despite guideline-based antiemetics. This multicenter exploratory single-arm two-stage trial evaluated patient-controlled, real-time transcutaneous electrical acupoint stimulation (TEAS) at Neiguan (PC6) as an adjunct to standard antiemetic therapy in patients with breast cancer. Forty-eight patients who had experienced CINV and were scheduled at enrollment to receive the same chemotherapy and antiemetic regimens during two consecutive cycles were analyzed. Cycle 1 served as the observation period, and cycle 2 added on-demand wrist-worn TEAS initiated by patients at nausea or vomiting onset during 0-120 h after chemotherapy. Compared with the observation period, TEAS was associated with lower nausea frequency and visual analogue scale scores on days 1-5 and higher nausea response rates on days 1-4. Vomiting frequency and severity were lower on days 1-3, but between-period differences were not significant on days 4-5. SF-36 scores increased and SAS/SDS scores decreased on day 5. Two transient local numbness events occurred, with no serious TEAS-related adverse events. These findings suggest that patient-controlled TEAS is feasible and warrants confirmation in randomized sham-controlled trials.

Breaches of epithelial homeostasis trigger an inflammatory response. Not only initiation but also negative regulation of the response is critical, as autoinflammation can cause tissue damage and chronic disease. Epithelial breaches can be signaled by damage-associated molecular patterns (DAMPs), including basement membrane (BM) degradation, that attract inflammatory cells. Here, we show that the conserved glycosylphosphatidylinositol-linked thioester-containing protein Tep3 from Drosophila, the ortholog of human CD109, limits innate immune cell attachment to damaged and transformed epithelia. Tep3 is induced in wounds alongside the matrix metalloprotease 1 (MMP1). Tep3 inhibits MMP1 proteolytic activity, reducing production of a BM DAMP that triggers macrophage association. A Drosophila tumor up-regulates Tep3 to limit an MMP1- and macrophage-dependent antitumor immune response, thus accelerating progression and host death. Hence, fly tumors can exploit a physiological anti-inflammatory axis to pathologically limit their immune restriction.

In view of the rapidly increasing evidence that gene fusion mutations are frequent drivers of cancer, a deeper understanding of the molecular and functional hallmarks of specific gene fusions in epithelial ovarian cancer (EOC) is essential. In this work we sought to identify the molecular signature of the BCAM-AKT2 fusion protein in ovarian cancer cell lines and to assess the biological impact of the novel fusion in these cells. Our in-vitro results show that the BCAM-AKT2 fusion protein is engaged in proliferative action within EOC cell lines. Furthermore, RNA-seq analysis shows that the effect of BCAM-AKT2 in SKOV3 cells is associated with activated unfolded protein response (UPR) and with the inhibition of interferon alpha and beta signaling pathways, pyropstosis and viral response in EOC cell lines. Overall, our results indicate that in SKOV3 cells, BCAM-AKT2 modulates the UPR signaling pathway, which is known to interact with oncogene and tumor suppressor networks during cancer development. These findings offer fresh insights suggesting that BCAM-AKT2 could serve as a promising target for therapeutic interventions in ovarian cancer.

Desmoglein 3 (Dsg3), a desmosomal cadherin, is aberrantly expressed in oral squamous cell carcinoma (OSCC), although its role remains controversial. Higher Dsg3 expression has been reported in metastatic lymph nodes compared with primary tumors. This study aimed to clarify the role of Dsg3 under anchorage-dependent (AD) and anchorage-independent (AID) conditions. Cell lines derived from primary tumors (P) and metastatic lymph nodes (LY) of three OSCC patients, along with two commercial OSCC cell lines, were analyzed for proliferation, migration, and multicellular aggregate (MCA) formation. Differentially expressed genes (DEGs) following Dsg3 knockdown were also examined, followed by Gene Ontology (GO) analysis. Under AD conditions, Dsg3-low cells showed significantly higher proliferation and migration than Dsg3-high cells (p < 0.05). In contrast, under AID conditions, Dsg3 expression was markedly upregulated (up to 50-fold), and Dsg3-high cells exhibited enhanced proliferation. However, Dsg3 knockdown significantly increased proliferation under AD conditions but had no significant effect under AID conditions. Instead, under AID conditions, Dsg3 knockdown significantly reduced aggregate size and increased variability in circularity, indicating impaired structural organization of MCAs. Consistent with these findings, DEG analysis revealed no enrichment of apoptosis- or cell cycle-related pathways under AID conditions. GO analysis indicated that DEGs under AD conditions were associated with macromolecule biosynthesis, whereas those under AID conditions were related to gene expression and nucleic acid biosynthesis. These results indicate that Dsg3 exerts anchorage-dependent functions in OSCC, suppressing proliferation under AD conditions while contributing to the structural organization of multicellular aggregates under AID conditions. This context-dependent role may underlie the paradoxical effects of Dsg3 and facilitate tumor adaptation to metastatic environments.

High-risk (HR) neuroblastoma (NB) remains a leading cause of pediatric cancer mortality, frequently driven by MYCN amplification or MYC overexpression. Despite their central role, direct pharmacological targeting of these transcription factors remains clinically challenging. Here, we identify CaM kinase-like vesicle-associated protein (CAMKV) as a MYCN/MYC-regulated effector of NB pathogenesis. Although previously classified as a nonfunctional pseudokinase, we demonstrate that CAMKV possesses intrinsic kinase activity that is essential for tumor growth. Analysis of patient datasets and primary tumors shows that elevated CAMKV expression correlates with advanced disease stage and poor overall survival. Through integrated transcriptomics, ChIP-seq, and phosphoproteomics, we establish CAMKV as a central signaling hub that coordinates metabolic and proliferative pathways. Both genetic depletion and small-molecule inhibition of CAMKV significantly impair NB cell proliferation in vitro and suppress tumor growth in vivo. Collectively, our findings establish CAMKV as a unifying therapeutic vulnerability and highlight this functional kinase as a promising target for translational development in HR NB.

Antisense long non-coding RNAs (lncRNAs) may fine-tune expression of their overlapping sense genes in cancer. DIAPH3-AS1, HMMR-AS1, and SPATA3-AS1 remain uncharacterized in colorectal cancer (CRC), and SPATA3-AS1 has not been studied in any malignancy.

Ninety CRC patients were enrolled, with paired tumor biopsies collected before and after capecitabine-based chemotherapy; 71 healthy individuals served as controls. Expression of the three lncRNAs was measured by qRT-PCR and normalized to β-actin (2 - ΔCt method). Group and paired comparisons used the Mann-Whitney U and Wilcoxon signed-rank tests, and diagnostic value was assessed by ROC analysis. All three lncRNAs were significantly overexpressed in pre-treatment CRC tissue versus healthy mucosa (fold-changes 2.22-2.87; p < 0.001). After chemotherapy, HMMR-AS1 fell significantly (1.60-fold, p = 0.0012), becoming indistinguishable from controls (p = 0.133), whereas DIAPH3-AS1 and SPATA3-AS1 remained elevated. HMMR-AS1 was also higher in well/moderately differentiated than poorly differentiated tumors (p = 0.0067); none of the three transcripts was associated with TNM stage, lymph node metastasis, tumor site, or treatment response. ROC analysis showed modest baseline discrimination (AUC 0.652-0.699), and HMMR-AS1's diagnostic performance declined after treatment (AUC 0.569), consistent with its chemo-responsiveness.

DIAPH3-AS1, HMMR-AS1, and SPATA3-AS1 are consistently upregulated in CRC tissue at diagnosis, but only HMMR-AS1 is sensitive to chemotherapy and differentiation grade, indicating transcript-specific roles for antisense lncRNAs in CRC biology.

Sympathetic noradrenergic stimuli are transduced at the systemic and cellular level through multiple adrenergic receptor subtypes, the predominant of which is the β₂-adrenoceptor (β₂-AR). In female-specific hormone-sensitive cancers like breast cancer, the effects of adrenergic stimulation and altered hormone sensitivity on cancer cell survival signaling in the context of estrogen receptor (ER) status-dependent cellular responsiveness remain incompletely understood. ER-positive (MCF-7) and ER-negative (MDA-MB-231) breast cancer cell lines were cultured in vitro and treated with the β₂-AR specific agonist terbutaline (10^- 6 M and 10^- 9 M) and non-selective β-AR antagonist propranolol (10^- 5M) to examine their effects on proliferation by cell cycle analysis, expression of pro-angiogenic (VEGF-A, VEGF-C) and signaling (p-ERK, p-CREB) molecules by ELISA, nitric oxide (NO) production by Griess assay, and miRNA expression (miR-21, miR-191) by RT-qPCR. Terbutaline elicited distinct and opposing cellular responses depending on ER status, enhancing proliferation, VEGF-C expression, miR-191 levels, and p-ERK signaling in ER-positive MCF-7 cells, while attenuating proliferation, VEGF-C expression, miR-191 levels, and p-ERK signaling in ER-negative MDA-MB-231 cells. In contrast, p-CREB signaling was enhanced in both cell lines. VEGF-A expression was downregulated in both cell lines, whereas NO production and miR-21 expression were increased in an ER-independent manner, suggesting involvement of β-adrenergic signaling mechanisms beyond direct ER mediation. Propranolol significantly attenuated terbutaline-induced effects in both cell lines, with greater magnitude of inhibition observed in ER-positive cells. These findings demonstrate that β2-AR-mediated regulation of proliferation, angiogenic signaling, and epigenetic modulators in breast cancer cells is differentially modulated by ER status, likely through selective engagement of ERK- and CREB-dependent signaling pathways. While ER-dependent crosstalk contributes to divergent outcomes, ER-independent β-adrenergic mechanisms may also play a role, underscoring the complexity of adrenergic signaling in breast cancer progression.

MicroRNAs (miRNAs) are small non-coding RNAs whose function is to regulate gene expression post-transcriptionally. Transcription factors (TFs) are the DNA-binding proteins responsible for activation or repression of a gene. Together, miRNAs and TFs form regulatory networks that modulate cellular homeostasis. In these regulatory networks, these TFs often regulate the expression of miRNAs, and in turn, miRNAs regulate the expression of TFs, thus forming feedback and feedforward loops. These loops and regulatory networks allow precise control over gene expression patterns by enabling accurate signal processing. Utilizing mathematical modelling and machine learning approaches helps understand the global structure of these networks. These reveal cellular fate selection, stress adaptation, disease development, and gaining insights into these interconnected regulatory systems opens new prospects for novel biomarker discovery and therapeutic approaches in a variety of disciplines, including cancer and immunotherapy.