N-(4-Aminobutyl)-N-ethylisopropanol and Co2+ Dual-Functionalized Core-Shell Fe3O4@Au/Ag Magnetic Nanomaterials with Strong and Stable Chemiluminescence for a Label-Free Exosome Immunosensor.

Recently, magnetic beads (MBs) are moving toward chemiluminescence (CL) functional magnetic nanomaterials with a great potential for constructing label-free immunosensors. However, most of the CL-functionalized MBs suffer from scarce binding sites, easy aggregation, and leakage of CL reagents, which will ultimately affect the analytical performance of immunosensors. Herein, by using core-shell Fe3O4@Au/Ag magnetic nanomaterials as a nanoplatform, a novel N-(4-aminobutyl)-N-ethylisopropanol (ABEI) and Co2+ dual-functionalized magnetic nanomaterial, namely, Fe3O4@Au/Ag/ABEI/Co2+, with strong and stable CL emission was successfully synthesized. Its CL intensity was 36 and 3.5 times higher than that of MB@ABEI-Au/Co2+ and ABEI and Co2+ dual-functionalized chemiluminescent MBs previously reported by our group, respectively. It was found that the excellent CL performance of Fe3O4@Au/Ag/ABEI/Co2+ could be attributed to the enrichment effect of the Au/Ag shell and the synergistic enhance effect of the Au/Ag shell and Co2+. A related CL mechanism has been proposed. Afterward, based on the intense and stable CL emission of Fe3O4@Au/Ag/ABEI/Co2+, a sensitive and effective label-free CL immunosensor for exosome detection was established. It exhibited excellent analytical performance with a wide detection range of 3.1 × 103 to 3.1 × 108 particles/mL and a low detection limit of 2.1 × 103 particles/mL, which were better than the vast majority of the reported CL immunosensors. Moreover, the proposed label-free CL immunosensor was successfully used to detect exosomes in human serum samples and enabled us to distinguish healthy persons and lung cancer patients. It has the potential to be a powerful tool for exosome study and early cancer diagnosis.

Sintilimab Plus Modified FOLFIRINOX in Metastatic or Recurrent Pancreatic Cancer: The Randomized Phase II CISPD3 Trial.

BACKGROUND: Folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or modified FOLFIRINOX (mFFX) is the first-line standard of care for metastatic pancreatic adenocarcinoma; effective and safe treatment strategies are needed as survival remains poor. Sintilimab, a human immunoglobulin G4 monoclonal antibody for programmed cell death-1, has shown efficacy in various cancers. We evaluated the efficacy and safety of sintilimab with mFFX for metastatic/recurrent pancreatic ductal adenocarcinoma in China. PATIENTS AND METHODS: This was a single-center, randomized, controlled, open-label phase II study. Patients were assigned 1:1 to sintilimab + mFFX or mFFX (n = 55, each). RESULTS: In the intention-to-treat population, median overall survivals (primary endpoint) were similar in the sintilimab + mFFX and mFFX groups: 10.9 and 10.8 months, respectively [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.69-1.68]. The objective response rate was higher [50.0% (95% CI 34.6-65.4%) versus 23.9% (95% CI 11.1-36.7%)] in the sintilimab + mFFX group (P < 0.05). Median (HR, 95% CI) progression-free survival and disease control rates (95% CI) were also similar at 5.9 and 5.7 months (0.93, 0.62-1.40), and 84.1% (72.8-95.3%) and 71.7%, (58.2-85.3%), respectively. Incidences of grade ≥ 3 treatment-emergent adverse events were 84.9% (45/53) and 74.1% (40/54), and that of grade ≥ 3 immune-related adverse events were 5.7% (3/53) and 0 in each group, respectively. CONCLUSIONS: The study did not meet its primary endpoint, no clear survival benefit was observed, and the benefit of sintilimab + mFFX for advanced pancreatic cancer was not supported; however, the findings suggest that using this regimen for pancreatic cancer is feasible, has an acceptable safety profile, and leads to an objective response rate of 50%. Trial registration ClinicalTrials.Gov; NCT03977272.

A preoperative nomogram predicts prognosis of patients with hepatocellular carcinoma after liver transplantation: a multicenter retrospective study.

BACKGROUND: Although criteria for liver transplantation, such as the Milan criteria and Hangzhou experiences, have become popular, criteria to guide adjuvant therapy for patients with hepatocellular carcinoma after liver transplantation are lacking. METHODS: We collected data from all consecutive patients from 2012 to 2019 at three liver transplantation centers in China retrospectively. Univariate and multivariate analyses were used to analyze preoperative parameters, such as demographic and clinical data. Using data obtained in our center, calibration curves and the concordance Harrell's C-indices were used to establish the final model. The validation cohort comprised the patients from the other centers. RESULTS: Data from 233 patients were used to construct the nomogram. The validation cohort comprised 36 patients. Independent predictors of overall survival (OS) were identified as HbeAg positive (P = 0.044), blood-type compatibility unmatched (P = 0.034), liver transplantation criteria (P = 0.003), and high MELD score (P = 0.037). For the validation cohort, to predict OS, the C-index of the nomogram was 0.874. Based on the model, patients could be assigned into low-risk (≥ 50%), intermediate-risk (30-50%), and high-risk (≤ 30%) groups to guide adjuvant therapy after surgery and to facilitate personalized management. CONCLUSIONS: The OS in patients with hepatocellular carcinoma after liver transplantation could be accurately predicted using the developed nomogram.

The Wnt3a/ß-catenin/TCF7L2 signaling axis reduces the sensitivity of HER2-positive epithelial ovarian cancer to trastuzumab.

Epithelial ovarian cancer (EOC) is one of the most common and lethal gynecological cancers. Novel therapeutic agents have been developed for EOC, but patient survival remains poor. Trastuzumab has been approved for breast and gastric cancers with high expression of human epidermal growth factor receptor 2 (HER2), but it has not achieved any clinical success in EOC. Dysregulated Wnt/ß-catenin signaling is involved in cancer development, but whether it plays a role in EOC resistance to trastuzumab remains largely unknown. Here, we observed that high expression of Wnt3a, ß-catenin and TCF7L2, which can form a signaling axis in the Wnt/ß-catenin pathway, commonly existed in HER2-positive EOC tissue samples and was correlated with a poor patient prognosis. Cell proliferation and migration assays and nude mouse xenograft model experiments demonstrated that the Wnt3a/ß-catenin/TCF7L2 signaling axis promoted tumor cell growth and metastasis and reduced tumor sensitivity to trastuzumab. Analysis of downstream Akt signaling suggested that the function of the Wnt3a/ß-catenin/TCF7L2 signaling axis was mediated, at least in part, through increasing Akt phosphorylation. Overall, this study reveals a crucial role for the Wnt3a/ß-catenin/TCF7L2 signaling axis in EOC resistance to trastuzumab and the potential application of HER2-targeted drugs combined with inhibitors of this signaling axis for EOC treatment.

Development of a Novel Multiparametric MRI Radiomic Nomogram for Preoperative Evaluation of Early Recurrence in Resectable Pancreatic Cancer.

BACKGROUND: In pancreatic cancer, methods to predict early recurrence (ER) and identify patients at increased risk of relapse are urgently required. PURPOSE: To develop a radiomic nomogram based on MR radiomics to stratify patients preoperatively and potentially improve clinical practice. STUDY TYPE: Retrospective. POPULATION: We enrolled 303 patients from two medical centers. Patients with a disease-free survival ≤12 months were assigned as the ER group (n = 130). Patients from the first medical center were divided into a training cohort (n = 123) and an internal validation cohort (n = 54). Patients from the second medical center were used as the external independent validation cohort (n = 126). FIELD STRENGTH/SEQUENCE: 3.0T axial T1 -weighted (T1 -w), T2 -weighted (T2 -w), contrast-enhanced T1 -weighted (CET1 -w). ASSESSMENT: ER was confirmed via imaging studies as MRI or CT. Risk factors, including clinical stage, CA19-9, and radiomic-related features of ER were assessed. In addition, to determine the intra- and interobserver reproducibility of radiomic features extraction, the intra- and interclass correlation coefficients (ICC) were calculated. STATISTICAL TESTS: The area under the receiver-operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and test groups. The results of decision curve analysis (DCA) indicated that the radiomic nomogram achieved the most net benefit. RESULTS: The AUC values of ER evaluation for the radiomics signature were 0.80 (training cohort), 0.81 (internal validation cohort), and 0.78 (external validation cohort). Multivariate logistic analysis identified the radiomic signature, CA19-9 level, and clinical stage as independent parameters of ER. A radiomic nomogram was then developed incorporating the CA19-9 level and clinical stage. The AUC values for ER risk evaluation using the radiomic nomogram were 0.87 (training cohort), 0.88 (internal validation cohort), and 0.85 (external validation cohort). DATA CONCLUSION: The radiomic nomogram can effectively evaluate ER risks in patients with resectable pancreatic cancer preoperatively, which could potentially improve treatment strategies and facilitate personalized therapy in pancreatic cancer. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;52:231-245.

The efficacy and toxicity of chemotherapy in the elderly with advanced pancreatic cancer.

OBJECTIVES: FOLFIRINOX (FFX) or abraxane plus gemcitabine (AG)-based chemotherapy is used widely as firstline treatment for patients with pancreatic cancer. However, their use in the elderly is discouraged because of adverse events. More clinical data about the therapeutic response and tolerability to FFX or AG in elderly patents (over 70 years old) are required. METHODS: Patients with advanced pancreatic cancer (n = 203; 131 metastatic pancreatic cancer patients (MPC) and 72 locally advanced pancreatic cancer patients (LAPC)) were treated using modified-FFX (mFFX) or AG and mFFX sequentially. The patients were grouped according to their age, patients below 70 years old and patients above 70 years old. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and adverse events were compared between the groups. RESULTS: The ORRs in the elderly and in patients below 70 were similar (30.0% versus 32.3%). The median OS and PFS were also similar between the groups (mOS 13.3 m vs 12.7 m, p = 0.729, HR 0.874 (95% CI 0.5310 to 1.438); mPFS mPFS 10.6 m vs 10.3 m, p = 0.363, HR 0.800 (95% CI 0.4954 to 1.293)). However, the elderly patients suffered a higher incidence of severe adverse events (50% vs. 28.3%). CONCLUSIONS: These data could provide guidance for chemotherapy use in elderly patients with advanced pancreatic cancer. Age did not affect treatment outcome; however, supportive treatment is very important for elderly patients receiving chemotherapy.

Knockdown of AGGF1 inhibits the invasion and migration of gastric cancer via epithelial-mesenchymal transition through Wnt/ß-catenin pathway.

BACKGROUND: Angiogenic factor with G-patch and FHA domain 1 (AGGF1), as a newly identified human angiogenic factor, is overexpressed in some types of malignant tumors and closely associated with patient's prognosis. However, the mechanisms involved in the regulation of AGGF1 in gastric cancer (GC) still remain unclear. METHODS: In this study, AGGF1 level in GC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). After knockdown of AGGF expression by RNA interference in GC cell lines MKN-45 and MGC-803, wound healing and transwell assays were conducted to examine the effects of AGGF1 on migration and invasion. Tumor growth was assessed in a mouse xenograft model in vivo. Furthermore, expression levels of epithelial-mesenchymal transition (EMT) biomarkers and involvement of the Wnt/ß-catenin pathway were detected by western blot and qRT-PCR. RESULTS: Compared to those in normal groups, the protein and mRNA of AGGF1 expression levels were significantly higher both in GC tissues and cell lines (all P < 0.05). Knockdown of AGGF1 dramatically inhibited the invasion and migration of MKN-45 and MGC-803 cells (all P < 0.01) in vitro, and suppressed the tumor growth of nude mice xenograft model in vivo. Western blot revealed alterations in EMT biomarkers, suggesting the role of AGGF1 in EMT. Moreover, we found that downregulated expression of AGGF1 attenuated Wnt/ß-catenin related protein expression. CONCLUSIONS: Collectively, knockdown of AGGF1 inhibits the invasion and migration of gastric cancer via epithelial-mesenchymal transition through Wnt/ß-catenin pathway.

Paraoxonase 3 is involved in the multi-drug resistance of esophageal cancer.

BACKGROUND: Drug resistance prevents the effective treatment of cancers. DNA methylation has been found to participate in the development of cancer drug resistance. METHODS: We performed the wound-healing and invasion assays to test the effect of the paraoxonase gene PON3 on esophageal cancer (EC) cells. In addition, in vivo EC-derived tumor xenografts in nude mice were generated to test the effect of PON3 on the chemoresistance of EC cells. RESULTS: We found that PON3 is hypermethylated in drug-resistant EC cell line K150, which in-return down-regulates its expression. The following experiments by the forced changes of PON3 level in vitro and in vivo demonstrated that the PON3 expression negatively correlates with drug resistance in EC cells. Further wound-healing and invasion assays showed that PON3 suppresses the migration and invasion of EC cells. CONCLUSION: Our data established that PON3 is associated with the EC drug resistance, which may serve as a biomarker for the potential therapeutic treatment of EC.

MiR-20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells.

BACKGROUND: MicroRNAs (miRNAs) was reported to be involved in cancer radio-resistance, which remains a major obstacle for effective cancer therapy. METHODS: The differently expressed miRNAs were detected by RNA-seq experiment in nasopharyngeal cancer (NPC) cells. MiR-20a-5p was selected as our target, which was subject to finding its target gene Rab27B via bioinformatics analysis. The qRT-PCR, western blot and the luciferase reporter assays were performed to confirm Rab27B as the target of miR-20a-5p. In addition, the roles of miR-20a-5p in NPC radio-resistance were detected by transfection of either miR-20a-5p-mimic or miR-20a-5p-antagomiR. The involvement of Rab27B with NPC radio-resistance was also detected by the experiments with siRNA-mediated repression of Rab27B or over-expression of GFP-Rab27B. Wound healing and invasion assays were performed to detect the roles of both miR-20a-5p and Rab27B. RESULTS: MiR-20a-5p promotes NPC radio-resistance. We identified that its target gene Rab27B negatively correlates with miR-20a-5p-mediated NPC radio-resistance by systematic studies of a radio-sensitive (CNE-2) and resistant (CNE-1) NPC cell lines. Repression of Rab27B by siRNA suppresses cell apoptosis and passivates CNE-2 cells, whereas over-expression of Rab27B triggered cell apoptosis and sensitizes CNE-1 cells. CONCLUSIONS: MiR-20a-5p and its target gene Rab27B might be involved in the NPC radio-resistance. Thus the key players and regulators involved in this pathway might be the potential targets for developing effective therapeutic strategies against NPC.

RhPt flowerlike bimetallic nanocrystals with tunable composition as superior electrocatalysts for methanol oxidation.

For the first time, composition-tunable, high-yield, RhPt flowerlike bimetallic nanocrystals were successfully synthesized through an aqueous solution approach. The electrocatalytic activity of these RhPt nanoalloys toward methanol oxidation was investigated and compared to the activity of commercial Pt black and commercial Ru50Pt50/C. The RhPt flowerlike bimetallic nanoallys have shown composition-dependent and superior catalytic properties relative to those of commercial Pt black and commercial Ru50Pt50/C. The peak current density and mass current value of Rh19Pt81 nanoalloys are 0.75 mA cm(-2) and 0.12 mA µg(-1), respectively. For commercial Pt black, they are 0.48 mA cm(-2) and 0.074 mA µg(-1), and for commercial Ru50Pt50/C, they are 0.28 mA cm(-2) and 0.10 mA µg(-1). Moreover, the chronoamperometric measurements show that the RhPt flowerlike nanoalloys have excellent stability over commercial Pt black and commercial Ru50Pt50/C.

Identification and Validation of a Cancer-Testis Antigen-Related Signature to Predict the Prognosis in Stomach Adenocarcinoma.

Background: Stomach adenocarcinoma (STAD) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Cancer-testis antigens (CTAs) participate in the pathogenesis and development of multiple cancers and are aberrantly overexpressed in various types of cancer. This study aimed to develop a CTA-related gene signature (CTARSig) to predict prognosis in STAD patients and explore its underlying mechanisms. Methods: We performed differential and prognostic analyses of CTA-related genes and constructed a CTA-related signature (CTARSig) along with a novel nomogram to predict the prognosis of patients with STAD based on the Cox and The Least Absolute Shrinkage and Selection Operator. CTARSig was further validated in an external cohort (GSE84437). Additionally, univariate and multivariate Cox regression, as well as receiver operating characteristic (ROC) analyses, were performed to assess the CTARSig systematically. Single-sample gene set enrichment analysis and ESTIMATE were used to characterise the Tumor Immune Microenvironment (TIME) in patients with STAD. Furthermore, Gene Set Variation Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses revealed the biological functions and signalling pathways associated with CTARSig. Finally, the human gastric cancer cell lines, HCG-27 and AGS, were used for in vitro and in vivo experiments, respectively, to further validate the role of ELOVL4. Results: Eleven CTA-related genes were identified to construct the CTARSig. Kaplan-Meier curves, independent prognostic analysis, and ROC curves revealed that CTARSig could better predict survival in patients with STAD. Moreover, in our study, we demonstrated that ELOVL4 is upregulated in gastric cancer tissues and that its high expression is associated with poor survival. Additionally, in vitro and in vivo experiments demonstrated that ELOVL4 promotes the metastatic and invasive potential of STAD cells, suggesting it may be a potential therapeutic target for STAD. Conclusion: In this study, a novel signature associated with CTAs was constructed for STAD, which may be a good predictor of patient prognosis. Thus, ELOVL4 may be a potential therapeutic target for gastric cancer. This study provides new insights into the potential roles of CTAs in gastric cancer.

Comparison of various surrogate markers for venous congestion in predicting acute kidney injury following cardiac surgery: A cohort study.

BACKGROUND: Venous congestion has been demonstrated to increase the risk of acute kidney injury (AKI) after cardiac surgery. Although many surrogate markers for venous congestion are currently used in clinical settings, there is no consensus on which marker is most effective in predicting AKI. METHODS: We evaluated various markers of venous congestion, including central venous pressure (CVP), inferior vena cava (IVC) diameter, portal pulsatility fraction (PPF), hepatic vein flow pattern (HVF), intra-renal venous flow pattern (IRVF), and venous excess ultrasound grading score (VExUS) in adult patients undergoing cardiac surgery to compare their ability in predicting AKI. RESULTS: Among the 230 patients enrolled in our study, 53 (23.0%) developed AKI, and 11 (4.8%) required continuous renal replacement therapy (CRRT). Our multivariate logistic analysis revealed that IRVF, PPF, HVF, and CVP were significantly associated with AKI, with IRVF being the strongest predictor (odds ratio [OR] 2.27; 95% confidence interval [CI], 1.38-3.73). However, we did not observe any association between these markers and CRRT. CONCLUSION: Venous congestion is associated with AKI after cardiac surgery, but not necessarily with CRRT. Among the markers tested, IRVF exhibits the strongest correlation with AKI.

Modeling Colorectal Cancer-Induced Liver Portal Vein Microthrombus on a Hepatic Lobule Chip.

Colorectal cancer is one of the most common malignant tumors. At the advanced stage of colorectal cancer, cancer cells migrate with the blood to the liver from the hepatic portal vein, eventually resulting in a portal vein tumor thrombus (PVTT). To date, the progression of the early onset of PVTT [portal vein microthrombus (PVmT) induced by tumors] is unclear. Herein, we developed an on-chip PVmT model by loading the spheroid of colorectal cancer cells into the portal vein of a hepatic lobule chip (HLC). On the HLC, the progression of PVmT was presented, and early changes in metabolites of hepatic cells and in structures of hepatic plates and sinusoids induced by PVmT were analyzed. We replicated intrahepatic angiogenesis, thickened blood vessels, an increased number of hepatocytes, disordered hepatic plates, and decreased concentrations of biomarkers of hepatic cell functions in PVmT progression on a microfluidic chip for the first time. In addition, the combined therapy of thermo-ablation and chemo-drug for PVmT was preliminarily demonstrated. This study provides a promising method for understanding PVTT evolution and offers a valuable reference for PVTT therapy.

The cancer/testis antigen HORMAD1 promotes gastric cancer progression by activating the NF-κB signaling pathway and inducing epithelial-mesenchymal transition.

OBJECTIVES: HORMAD1 is a cancer/testis antigen (CTAs) that regulates DNA homologous recombination, mismatch repair, and other tumor characteristics. However, its role and regulatory mechanisms in gastric cancer remain unclear. METHODS: We performed transcriptomic profiling on seven gastric cancers and paired tissues; HORMAD1 was significantly upregulated in gastric cancer samples and was related to poor prognosis survival. Furthermore, cancer pathway microarray, bioinformatic analysis, western blot, and immunochemistry assay demonstrated that HORMAD1 affected the NF-κB signaling pathway. RESULTS: In vitro and vivo studies confirmed that HORMAD1 knockdown inhibited cell growth and invasion, whereas overexpression reversed these effects. Mechanistically, HORMAD1 regulates the epithelial-mesenchymal transition process (EMT) via the NF-κB pathway by increasing the phosphorylation levels of NF-κB (p-65) and Iκκ-ß. Downstream target genes of the NF-κB signaling pathway, such as c-Myc, CyclinD1, may be involved in HORMAD1-induced tumorigenesis in gastric cancer (GC). CONCLUSIONS: HORMAD1 plays an important role in gastric cancer progression and could be a promising prognostic biomarker and therapeutic target.

Corrigendum: The association of insufficient gestational weight gain in women with gestational diabetes mellitus with adverse infant outcomes: a case-control study.

[This corrects the article DOI: 10.3389/fpubh.2023.1054626.].

V-Set and immunoglobulin domain containing (VSIG) proteins as emerging immune checkpoint targets for cancer immunotherapy.

The development of immune checkpoint inhibitors is becoming a promising approach to fight cancers. Antibodies targeting immune checkpoint proteins such as CTLA-4 and PD-1 can reinvigorate endogenous antitumor T-cell responses and bring durable advantages to several malignancies. However, only a small subset of patients benefit from these checkpoint inhibitors. Identification of new immune checkpoints with the aim of combination blockade of multiple immune inhibitory pathways is becoming necessary to improve efficiency. Recently, several B7 family-related proteins, TIGIT, VSIG4, and VSIG3, which belong to the VSIG family, have attracted substantial attention as coinhibitory receptors during T-cell activation. By interacting with their corresponding ligands, these VSIG proteins inhibit T-cell responses and maintain an immune suppressive microenvironment in tumors. These results indicated that VSIG family members are becoming putative immune checkpoints in cancer immunotherapy. In this review, we summarized the function of each VSIG protein in regulating immune responses and in tumor progression, thus providing an overview of our current understanding of VSIG family members.

Utility and specificity of plasma heat shock protein 90 alpha, CEA, and CA199 as the diagnostic test in colorectal cancer liver metastasis.

Background: Plasma heat shock protein 90 alpha (Hsp90α) has been suggested as a novel biomarker for the diagnosis and prognosis of cancer. Carcinoembryonic antigen (CEA) and carbohydrate antigen199 (CA199) are traditional tumor biomarkers for colorectal cancer (CRC). Previous studies have shown that Hsp90α and the combination of Hsp90α and CEA are optimal biomarkers for CRC at an early stage. However, research on the use of Hsp90α alone or in combination with CEA and/or CA199 in diagnosing CRC development, particularly liver metastasis, is limited. This study sought to investigate the value of Hsp90α alone or in combination with CEA/CA199 in diagnosing CRC liver metastasis. Methods: The clinical data of 472 CRC patients were retrospectively analyzed, which were confirmed by clinical manifestations and a histopathological examination associated with an imaging diagnosis. The levels of Hsp90α, and CEA, and CA199 were assessed by enzyme-linked immunoassays and electrochemiluminescence immunoassays. Liver metastasis was diagnosed by imaging or pathology of the liver. Logistic regression models were used to analyze associations between Hsp90α, CEA, and CA199, and liver metastasis in CRC. The areas under the curves (AUCs) were used to compare the utility of Hsp90α, CEA, and CA199 in the diagnosis of CRC liver metastasis (CRLM). Additionally, we compared the diagnostic utility of the models, including the Hsp90α plus 1 of the other serum markers, and a combination of the 3 serum makers. Results: The plasma levels of Hsp90α, CEA, and CA199 were positively associated with a higher risk of CRLM [odds ratios (OR) ranging from 1.36-2.72]. The AUCs of CEA, CA199, and Hsp90α for CRLM were 0.80, 0.69, and 0.55, respectively. The AUCs for the combination of Hsp90α and CEA, combination of Hsp90α and CA199, combinations of Hsp90α, CEA, and CA199 were 0.75, 0.66, 0.76, respectively. The combination of Hsp90α, CEA, and CA199 did not improve the diagnostic utility for liver metastasis in CRC. Conclusions: The level of Hsp90α was elevated in CRC and was associated with CRLM. Thus, the Hsp90α is a potential biomarker for CRLM. CEA has the largest diagnostic utility for CRLM. Adding Hsp90α to CEA/CA199 did not improve their diagnostic utility for CRLM.

RUNX2 facilitates aggressiveness and chemoresistance of triple negative breast cancer cells via activating MMP1.

Breast cancer remains the most common malignancy in women and constantly threatens the lives of patients worldwide. State-of-the-art renewal has indicated the involvement of RUNX-associated transcription factor 2 (RUNX2) in tumorigenesis and cancer progression, yet the detailed information during breast cancer is largely obscure. Herein, we took advantage of breast cancer cell lines and in vivo tumorigenicity test as well as multifaceted phenotypic analyses (e.g., RNA-sequencing, ChIP and qRT-PCR assay) to verify the pathogenic mechanism of RUNX2 in triple negative breast cancer aggressiveness and chemoresistance. Strikingly, the proliferation, migration, invasion and chemoresistance of resistant cell lines in triple negative breast cancer was effectively suppressed by RUNX2 silencing, and the in vivo tumorigenicity was significantly weakened as well. Furthermore, with the aid of transcriptomic and bioinformatic analyses, we found MMP1 was highly expressed in triple negative breast cancer (TNBC) and showed a strong correlation with the poor prognosis of the patients, which was consistent with the expression pattern of RUNX2. Finally, by conducting ChIP and qRT-PCR assessment, we verified that RUNX2 functioned via directly binding to the specific motifs in the promoter of MMP1 and thus activating the transcriptional process. Collectively, our data demonstrated the facilitating effect of RUNX2 during triple negative breast cancer progression by directly orchestrating the expression of MMP1, which supplied overwhelming new references for RUNX2-MMP1 axis serving as a novel candidate for breast cancer diagnosis and treatment.

Nanomedicine in lung cancer: Current states of overcoming drug resistance and improving cancer immunotherapy.

Lung cancer is considered to cause the most cancer-related deaths worldwide. Due to the deficiency in early-stage diagnostics and local invasion or distant metastasis, the first line of treatment for most patients unsuitable for surgery is chemotherapy, targeted therapy or immunotherapy. Nanocarriers with the function of improving drug solubility, in vivo stability, drug distribution in the body, and sustained and targeted delivery, can effectively improve the effect of drug treatment and reduce toxic and side effects, and have been used in clinical treatment for lung cancer and many types of cancers. Here, we review nanoparticle (NP) formulation for lung cancer treatment including liposomes, polymers, and inorganic NPs via systemic and inhaled administration, and highlight the works of overcoming drug resistance and improving cancer immunotherapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.