PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.

A prognostic model built on amino acid metabolism patterns in HPV-associated head and neck squamous cell carcinoma.

OBJECTIVES: To compare amino acid metabolism patterns between HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) patients and identify key genes for a prognostic model. DESIGN: Utilizing the Cancer Genome Atlas dataset, we analyzed amino acid metabolism genes, differentiated genes between HPV statuses, and selected key genes via LASSO regression for the prognostic model. The model's gene expression was verified through immunohistochemistry in clinical samples. Functional enrichment and CIBERSORTx analyses explored biological functions, molecular mechanisms, and immune cell correlations. The model's prognostic capability was assessed using nomograms, calibration, and decision curve analysis. RESULTS: We identified 1157 key genes associated with amino acid metabolism in HNSCC and HPV status. The prognostic model, featuring genes like IQCN, SLC22A1, SYT12, and TLX3, highlighted functions in development, metabolism, and pathways related to receptors and enzymes. It significantly correlated with immune cell infiltration and outperformed traditional staging in prognosis prediction, despite immunohistochemistry results showing limited clinical identification of HPV-related HNSCC. CONCLUSIONS: Distinct amino acid metabolism patterns differentiate HPV-positive from negative HNSCC patients, underscoring the prognostic model's utility in predicting outcomes and guiding therapeutic strategies.

EN1 promotes lung metastasis of salivary adenoid cystic carcinoma by regulating the PI3K-AKT pathway and epithelial-mesenchymal transition.

BACKGROUND: Engrailed homeobox 1 (EN1) is a candidate oncogene that is epigenetically modified in salivary adenoid cystic carcinoma (SACC). We investigated the expression of EN1 in SACC tissues and cells, EN1 promoter methylation, and the role of EN1 in tumour progression in SACC. METHODS: Thirty-five SACC samples were screened for key transcription factors that affect tumour progression. In vitro and in vivo assays were performed to determine the viability, tumorigenicity, and metastatic ability of SACC cells with modulated EN1 expression. Quantitative methylation-specific polymerase chain reaction analysis was performed on SACC samples. RESULTS: EN1 was identified as a transcription factor that was highly overexpressed in SACC tissues, regardless of clinical stage and histology subtype, and its level of expression correlated with distant metastasis. EN1 promoted cell invasion and migration through epithelial-mesenchymal transition in vitro and enhanced SACC metastasis to the lung in vivo. RNA-seq combined with in vitro assays indicated that EN1 might play an oncogenic role in SACC through the PI3K-AKT pathway. EN1 mRNA levels were negatively correlated with promoter hypermethylation, and inhibition of DNA methylation by 5-aza-dC increased EN1 expression. CONCLUSIONS: The transcription factor EN1 is overexpressed in SACC under methylation regulation and plays a pivotal role in SACC progression through the PI3K-AKT pathway. These results suggest that EN1 may be a diagnostic biomarker and a potential therapeutic target for SACC.

Familial gigantiform cementoma with recurrent ANO5 p.Cys356Tyr mutations: Clinicopathological and genetic study with literature review.

BACKGROUND: Familial gigantiform cementoma (FGC) is a rare tumor characterized by the early onset of multi-quadrant fibro-osseous lesions in the jaws, causing severe maxillofacial deformities. Its clinicopathological features overlap with those of other benign fibro-osseous lesions. FGC eventually exhibits progressively rapid growth, but no suspected causative gene has been identified. METHODS: In this study, three patients with FGC were recruited, and genomic DNA from the tumor tissue and peripheral blood was extracted for whole-exome sequencing. RESULTS: Results showed that all three patients harbored the heterozygous mutation c.1067G > A (p.Cys356Tyr) in the ANO5 gene. Furthermore, autosomal dominant mutations in ANO5 at this locus have been identified in patients with gnathodiaphyseal dysplasia (GDD) and are considered a potential causative agent, suggesting a genetic association between FGC and GDD. In addition, multifocal fibrous bone lesions with similar clinical presentations were detected, including five cases of florid cemento-osseous dysplasia, five cases of polyostotic fibrous dysplasia, and eight cases of juvenile ossifying fibromas; however, none of them harbored mutations in the ANO5 gene. CONCLUSION: Our findings indicate that FGC may be an atypical variant of GDD, providing evidence for the feasibility of ANO5 gene testing as an auxiliary diagnostic method for complex cases with multiple quadrants.

Colloid Pattern of Salivary Mucinous Adenocarcinomas With Recurrent BRAF V600E Mutations.

The relationship between various patterns of mucin-producing salivary adenocarcinomas, including invasive salivary adenocarcinomas with mucinous differentiation, such as colloid and papillary carcinomas, remains unclear. Herein, we aimed to describe the clinicopathologic characteristics, immunophenotypes, molecular underpinnings, and clinical behavior of salivary mucinous adenocarcinomas (MA) to clarify their classification. We described a broad series of colloid and papillary patterns of MAs, indicating that papillary pattern presented papillary cystic proliferation of mucinous columnar cells as salivary intraductal papillary mucinous neoplasms with recurrent AKT1 E17K mutations, whereas colloid adenocarcinomas containing large mucinous pools or lakes around the malignant epithelial nests or islands harbored BRAF V600E mutations with worse prognosis. Typical morphologic structures, CK7(+), CK20(-), CDX2(-), p63(-), p40(-), MAML2 fluorescence in situ hybridization (-), AR(-), TTF-1(-), S100(-), mammaglobin(-), or S100/mammaglobin(+) with ETV6 fluorescence in situ hybridization (-) immunophenotype, and recurrent AKT1 E17K or BRAF V600E mutations may be defined. To our knowledge, this small series represents the first genetic study on a typical colloid pattern of MA, and our study with the spectrum documentation for MA in clinicopathologic characteristics, histologic and immunophenotypes, molecular features, and clinical behavior will allow for a better understanding of these rare but distinctive tumors.

Incidental Tongue Cancer Detected With Total-Body 13 N-NH 3 PET/CT.

ABSTRACT: A 68-year-old man with chest tightness underwent cardiac blood perfusion imaging on total-body 13 N-NH 3 PET/CT. Incidentally, mildly increased 13 N-NH 3 activity was observed in the left side of the body of the tongue. Pathological diagnosis proved to be mucosal squamous cell carcinoma.

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial.

BACKGROUND: Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. METHODS: This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450 mg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. FINDINGS: Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1-17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3-42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0-15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2-40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7-19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7-37·4). INTERPRETATION: Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. FUNDING: Akeso Biopharma. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Molecular mechanisms underlying the epigallocatechin-3-gallate-mediated inhibition of oral squamous cell carcinogenesis.

OBJECTIVES: To reveal the mechanisms underlying the epigallocatechin-3-gallate (EGCG)-mediated inhibition of carcinogenesis and the related regulatory signaling pathways. DESIGN: The effect of EGCG on the proliferation of OSCC cells was examined. SuperPred, ChEMBL, Swiss TargetPrediction, DisGeNET, GeneCards, and National Center for Biotechnology Information databases were used to predict the EGCG target genes and oral leukoplakia (OL)-related, oral submucosal fibrosis (OSF)-related, and OSCC-related genes. The binding of EGCG to the target proteins was simulated using AutoDock and PyMOL. The Cancer Genome Atlas (TCGA) dataset was subjected to consensus clustering analysis to predict the downstream molecules associated with these targets, as well as their potential functions and pathways. RESULTS: EGCG significantly inhibited OSCC cell proliferation (p < 0.001). By comparing EGCG target genes with genes linked to oral potentially malignant disorder (OPMD) and OSCC, a total of eleven potential EGCG target genes were identified. Furthermore, EGCG has the capacity to bind to eleven proteins. Based on consensus clustering and enrichment analysis, it is suggested that EGCG may hinder the progression of cancer by altering the cell cycle and invasive properties in precancerous lesions of the oral cavity. Some possible strategies for modifying the cell cycle and invasive properties may include EGCG-mediated suppression of specific genes and proteins, which are associated with cancer development. CONCLUSIONS: This study investigated the molecular mechanisms and signaling pathways associated with the EGCG-induced suppression of OSCC. The identification of specific pharmacological targets of EGCG during carcinogenesis is crucial for the development of innovative combination therapies involving EGCG.

Efficacy and safety of serplulimab plus nab-paclitaxel in previously treated patients with PD-L1-positive advanced cervical cancer: a phase II, single-arm study.

Objective: We report the efficacy and safety of serplulimab, a novel humanized anti-programmed death-1 antibody, plus nanoparticle albumin-bound (nab)-paclitaxel in previously treated patients with programmed death ligand-1 (PD-L1)-positive advanced cervical cancer. Methods: Patients diagnosed with PD-L1-positive (combined positive score ≥1) cervical cancer were enrolled in this single-arm, open-label, phase II study. They were given serplulimab 4.5 mg/kg for up to 2 years (35 dosing cycles) plus nab-paclitaxel 260 mg/m2 for up to six cycles once every 3 weeks. Primary endpoints were safety and objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST version 1.1. Secondary endpoints included ORR assessed by the investigator, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Between December 2019 and June 2020, 52 patients were screened and 21 were enrolled. IRRC-assessed ORR was 57.1% (95% confidence interval [CI] 34.0-78.2%); 3 (14.3%) patients achieved complete response and 9 (42.9%) partial response. The median DOR was not reached (NR) (95% CI 4.1-NR). IRRC-assessed median PFS was 5.7 months (95% CI 3.0-NR), and median OS was 15.5 months (95% CI 10.5-NR). Investigator-assessed ORR was 47.6% (95% CI 25.7-70.2%). Seventeen (81.0%) patients experienced grade ≥3 treatment-emergent adverse events. Grade ≥3 adverse drug reactions were reported in 7 (33.3%) patients. Immune-related adverse events occurred in 12 (57.1%) patients. Conclusions: In previously treated patients with PD-L1-positive advanced cervical cancer, serplulimab plus nab-paclitaxel provided durable clinical activity and a manageable safety profile. Clinical trial registration: ClinicalTrials.gov, identifier NCT04150575.

Notch activation promotes bone metastasis via SPARC inhibition in adenoid cystic carcinoma.

OBJECTIVES: We aimed to investigate bone metastasis induced by Notch signalling pathway dysregulation and to demonstrate that SPARC is a potential therapeutic target in adenoid cystic carcinoma (AdCC) with Notch dysregulation. MATERIALS AND METHODS: This retrospective study enrolled 144 AdCC patients. RNA-sequencing and enrichment analyses were performed using 32 AdCC samples. Osteonectin/SPARC and the Notch activation indicator Notch intracellular domain (NICD) were detected using immunohistochemistry. Cell proliferation and migration assays were conducted using stably NICD over-expressing cells. The effect of SPARC on osteoclast differentiation in NICD cells was investigated using western blotting, quantitative reverse transcription PCR, tartrate-resistant acid phosphatase staining and resorption assays. RESULTS: RNA-sequencing analysis showed that genes down-regulated in Notch-mutant AdCCs, such as SPARC, were enriched in ossification and osteoblast differentiation. Most (75/110, 68.2%) Notch1-wild-type AdCCs showed SPARC over-expression, whereas 30 out of 34 (88.2%) Notch1-mutant tumours showed low SPARC expression. SPARC over-expression was then found negatively to be correlated with NICD expression in 144 AdCCs. NICD over-expression promoted cell growth, migration and osteoclast differentiation, which could be partly reversed by exogenous SPARC. CONCLUSIONS: Notch activation in AdCC contributes to bone metastasis through SPARC inhibition. The study results suggest that SPARC may represent a prognostic biomarker and potential therapeutic target.

Analysis of the Correlation of Basic Fibroblast Growth Factor in Serum of Patients with Diffuse Large B-Cell Lymphoma with Clinicopathological Efficacy and International Prognostic Index.

The correlation of basic fibroblast growth factor (bFGF) in serum of patients with diffuse large B-cell lymphoma (DLBCL) with clinicopathological efficacy and International Prognostic Index (IPI) is analyzed. 115 DLBCL patients admitted to our hospital for treatment from June 2020 to June 2021 are selected as the DLBCL patient group, 65 healthy subjects who received physical examination in our hospital during the same period are selected as the healthy control group, and the serum bFGF levels of DLBCL group and healthy control group are observed before treatment. The experimental results show that the serum bFGF expression of DLBCL patients is decreased significantly after chemotherapy, and the serum bFGF expression of DLBCL patients is closely related to the treatment effect, disease progression, tumor invasion, and prognosis, which has important clinical significance for judging the disease, treatment effect, and prognosis of patients.

Adoptive tumor infiltrating lymphocytes cell therapy for cervical cancer.

Cervical cancer is one of the most common malignancies among females. As a virus-related cancer, cervical cancer has attracted a lot of attention to develop virus-targeted immune therapy, including vaccine and adoptive immune cell therapy (ACT). Adoptive tumor infiltrating lymphocytes (TILs) cell therapy has been found to be able to control advanced disease progression in some cervical cancer patients who have received several lines of treatment in a pilot clinical trial. In addition, sustainable therapeutic effect has been identified in some cases. The safety risks of TIL therapy for patients are minimal or at least manageable. In this review, we focused on the versatility of TILs and tried to summarize potential strategies to improve the therapeutic effect of TILs and discuss related perspectives.

Clinicopathological significance of HSP70 expression in gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Heat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential cancer biomarker. However, no consensus has been reached regarding its clinicopathological and prognostic significance in patients with gastric cancer. To address this gap, we performed a systematic review and meta-analysis. METHODS: We searched PubMed, Embase, and the Cochrane Library for full-text literature according to the eligibility criteria. We used the odds ratio and hazard ratio as the suitable parameters to evaluate the clinicopathological and prognostic significance of HSP70. The statistical analysis was performed using STATA 15.0. RESULTS: After inclusion and exclusion of studies based on the eligibility criteria, data of 1,307 patients with gastric cancer from 9 studies were finally included. The pooled outcomes implied that HSP70 expression was significantly correlated with higher differentiation degrees, intestinal gastric cancer, and lymphovascular invasion but not with age, gender, depth of invasion, Helicobacter pylori infection, lymph node invasion, TNM stages, and metastasis. The pooled HR showed no significant correlation between HSP70 expression and overall survival of gastric cancer patients. CONCLUSIONS: Our meta-analysis showed that HSP70 plays a complicated role in the development of gastric cancer. It may be directly engaged in tumour differentiation and distant invasion but cannot be considered a biomarker for predicting the prognosis of gastric cancer.

Apatinib treatment is effective for metastatic malignant phyllodes tumors of the breast: a case report.

BACKGROUND: We report a rare case of malignant phyllodes tumors (MPT) with partial response to apatinib. CASE PRESENTATION: A 26-year-old woman had a palpable mass in her right breast for over a year. After resection, pathology indicated malignant phyllodes tumor. Eleven months after surgery, she underwent reoperation for a lung nodule, which demonstrated lung metastasis. She refused chemotherapy and was rehospitalized six months later due to leg pain. Pelvic mass biopsy revealed metastatic malignant phyllodes tumor. After concurrent chemoradiotherapy of the pelvic mass, multiple lung metastases emerged. Subsequent treatment with apatinib 500 mg/day resulted in a reduction in mass size and partial response. She survived for more than 8 months. CONCLUSION: The present case showed the potential therapeutic effects of apatinib in patients with MPT.

Multifunctional superhydrophobic adsorbents by mixed-dimensional particles assembly for polymorphic and highly efficient oil-water separation.

Supra-wetting materials, especially superhydrophobic absorption materials, as an emerging advanced oil-water separation material have attracted extensive concern in the treatment of oil spillage and industrial oily wastewater. However, it is still a challenge to fabricate robust and multifunctional superhydrophobic materials for the multitasking oil-water separation and fast clean-up of the viscous crude oil by an environment-friendly and scalable method. Herein, a solid-solid phase ball-milling strategy without chemical reagent-free modification was proposed to construct heterogeneous superhydrophobic composites by using waste soot as the solid-phase superhydrophobic modifier. A series of covalent bond restricted soot-graphene (S-GN) or soot-Fe3O4 (S-Fe3O4) composite materials with a peculiar micro-nano structure are prepared. Through "glue+superhydrophobic particles" method, the prepared soot-based composite particles are facilely loaded on the porous skeleton of the sponge to obtain multifunctional superhydrophobic adsorbents. The reported superhydrophobic adsorbents exhibited robust chemical and mechanical stability, convenient magnetic collection, the high oil absorption capacity of 60-142 g g-1, durable recyclability (>250 cycles), efficient separation efficiency (>99.5%) and outstanding self-heated performance, which enable them to be competent for oil-water separation in multitasking and complex environment (floating oils, continuous oil collection, oil-in-water emulsion, and viscous oil-spills).

Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages.

Immunosuppressive tumor microenvironment (TME) and ascites-derived spheroids in ovarian cancer (OC) facilitate tumor growth and progression, and also pose major obstacles for cancer therapy. The molecular pathways involved in the OC-TME interactions, how the crosstalk impinges on OC aggression and chemoresistance are not well-characterized. Here, we demonstrate that tumor-derived UBR5, an E3 ligase overexpressed in human OC associated with poor prognosis, is essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines. UBR5 is also required to sustain cell-intrinsic ß-catenin-mediated signaling to promote cellular adhesion/colonization and organoid formation by controlling the p53 protein level. OC-specific targeting of UBR5 strongly augments the survival benefit of conventional chemotherapy and immunotherapies. This work provides mechanistic insights into the novel oncogene-like functions of UBR5 in regulating the OC-TME crosstalk and suggests that UBR5 is a potential therapeutic target in OC treatment for modulating the TME and cancer stemness.

Three-dimensional adsorbent with pH induced superhydrophobic and superhydrophilic transformation for oil recycle and adsorbent regeneration.

With the development of research on superwettability materials, superhydrophobic and superoleophilic materials show superior separation ability in oil-water separation due to their excellent oil-water selectivity. However, due to the super wetting ability of the oil to the material, it is difficult to clean and reuse after adsorbing the oil spill. Therefore, how to realize the complete regeneration of superhydrophobic and superoleophilic materials is still a worldwide problem. In this paper, the controlled adsorption-desorption process of oil and the complete regeneration of materials are realized by pH induced superwettability transformation. We fabricate a pH-responsive oil-water separation sponge by a method of simply impregnating the carboxyl and alkyl group modified SiO2 nanoparticles on the surface of melamine sponge (MS) skeleton, which can change the wettability from superhydrophobicity and superhydrophilicity through protonation and deprotonation in different pH solutions. The experiment results indicate that the sponge is superhydrophobic and superoleophilic in acid and neutral solution, and can adsorb oil in water. While in basic solution, it becomes superhydrophilic and underwater superoleophobic, which can release the adsorbed oil. With the help of a vacuum pump, we can use this wettability transition to achieve a continuous oil adsorption and desorption process. These findings offer a new preparation method of regenerative 3D adsorption materials like MS in oil-water separation.

BUB1 promotes proliferation of liver cancer cells by activating SMAD2 phosphorylation.

Budding uninhibited by benzimidazoles 1 (BUB1) is a mitotic checkpoint serine/threonine kinase that has been reported as an oncogene or tumor suppressor gene in various types of cancer, including breast cancer, pancreatic ductal adenocarcinoma, prostate and gastric cancers. However, its role in liver cancer remains unclear. The present study aimed to explore the biological function of BUB1 in liver cancer. The present study demonstrated that BUB1 mRNA expression levels and the intensity of immunohistochemical staining were significantly increased in liver cancer tissues compared with normal tissues. The role of BUB1 in cell proliferation was also determined. Overexpression of BUB1 significantly promoted cell proliferation, whereas knockdown of BUB1 expression inhibited the proliferation of liver cancer cell lines. In experiments investigating the underlying mechanism, overexpression of BUB1 increased the levels of SMAD2 phosphorylation, whereas knockdown of BUB1 reduced the levels of SMAD2 phosphorylation. Therefore, BUB1 may promote proliferation of liver cancer cells by activating phosphorylation of SMAD2, and BUB1 may serve as a potential target in the diagnosis and/or treatment of liver cancer.

Hierarchically Active Poly(vinylidene fluoride) Membrane Fabricated by In Situ Generated Zero-Valent Iron for Fouling Reduction.

Sodium hypochlorite (NaClO) solution is a typical cleaning agent for membrane fouling. However, it can damage membrane chemical structures and produce toxic disinfection byproducts, which in turn reduces the membrane performance. This study focuses on the fabrication of active membranes thereby overcoming the limitations of chemical cleaning. A hierarchical active poly(vinylidene fluoride) membrane with polydopamine/polyethyleneimine (PEI) co-supported iron nanoparticle (Fe NP) catalysts was successfully constructed and denoted as a Fe-HP-membrane. The Fe-HP-membrane exhibited excellent advanced oxidation activity with maximum flux recoveries (∼85% with bovine serum albumin [BSA] and ∼95% with humic acid [HA] solutions). After the static experiment of ∼30 days, the BSA proteins and HA successfully desorbed from the membrane surface. Especially, with a trace amount of hydrogen peroxide (H2O2) flowing over the surface of the Fe-HP-membrane, highly exposed active sites were observed. Membrane cleaning showed that the "outside-to-in" active surfaces generated considerable amounts of •OH radicals at the interface of BSA or HA and the fouled membrane. As a result, the unwanted foulants were successfully removed from the membrane interface, enabling multiple use of the Fe-HP-membrane. Therefore, backwashing with a small amount of H2O2 (0.33 wt %) covered ∼20% of the flux. In contrary, backwashing with NaClO (1 wt %) can only achieve a flux recovery of ∼10% after six consecutive BSA filtration cycles. The Fe-HP-membrane exhibited better HA foulant removal (a flux recovery of ∼51%) after backwashing with H2O2 than using NaClO (a flux recovery of ∼43%). Our findings demonstrate a new platform for water treatment and regeneration of fouled membranes.

Strain elastography as an early predictor of long-term prognosis in patients with locally advanced cervical cancers treated with concurrent chemoradiotherapy.

OBJECTIVE: To explore the value of strain elastography as an early predictor of long-term prognosis in patients with locally advanced cervical cancers treated with concurrent chemoradiotherapy (CCRT). METHODS: Strain elastography examinations were performed on 45 patients with locally advanced cervical cancers at 3 time points: prior to CCRT, and at 1 and 2 weeks after the start of CCRT. The maximum tumor diameter (Dmax), strain ratio (SR), and their percentage changes (ΔDmax and ΔSR) were calculated to predict long-term prognosis. Based on the results of physical examinations, Papanicolaou test, and pelvic magnetic resonance imaging, we classified patients into two groups: responders (complete remission) and non-responders (sustained disease, recurrence, or death). RESULTS: After a median follow-up of 30 months (range, 12-36 months), 36 of 45 (80%) patients were disease free. The Dmax as well as ΔDmax at 2 weeks during CCRT was able to predict the responder outcomes, with an area-under-the-curve (AUC) of 0.733 and 0.731, respectively. Furthermore, significant differences in SR and ΔSR at 1 and 2 weeks during therapy were shown between the responder and non-responder groups (all p < 0.05), and ΔSR at 2 weeks during CCRT presented with the highest AUC (0.91), yielding 88.9% sensitivity and 88.9% specificity with a selected cutoff value. CONCLUSIONS: Strain elastography may be useful as an early predictor of long-term outcomes after CCRT for patients with cervical cancer. KEY POINTS: • The D maxas well as ΔD maxat 2 weeks during CCRT can predict the responder outcomes. • The elastography parameters (SR and ΔSR) exhibited predictive values of favorable response after therapy initiation. • ΔSR at 2 weeks during CCRT held the best predictive value for the responder outcomes.