Recent advances in pluripotent stem cell-derived cardiac organoids and heart-on-chip applications for studying anti-cancer drug-induced cardiotoxicity.

Cardiovascular disease (CVD) caused by anti-cancer drug-induced cardiotoxicity is now the second leading cause of mortality among cancer survivors. It is necessary to establish efficient in vitro models for early predicting the potential cardiotoxicity of anti-cancer drugs, as well as for screening drugs that would alleviate cardiotoxicity during and post treatment. Human induced pluripotent stem cells (hiPSCs) have opened up new avenues in cardio-oncology. With the breakthrough of tissue engineering technology, a variety of hiPSC-derived cardiac microtissues or organoids have been recently reported, which have shown enormous potential in studying cardiotoxicity. Moreover, using hiPSC-derived heart-on-chip for studying cardiotoxicity has provided novel insights into the underlying mechanisms. Herein, we summarize different types of anti-cancer drug-induced cardiotoxicities and present an extensive overview on the applications of hiPSC-derived cardiac microtissues, cardiac organoids, and heart-on-chips in cardiotoxicity. Finally, we highlight clinical and translational challenges around hiPSC-derived cardiac microtissues/organoids/heart-on chips and their applications in anti-cancer drug-induced cardiotoxicity. • Anti-cancer drug-induced cardiotoxicities represent pressing challenges for cancer treatments, and cardiovascular disease is the second leading cause of mortality among cancer survivors. • Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology. • Emerging evidence supports that hiPSC-derived cardiac organoids and heart-on-chip are promising in vitro platforms for predicting and minimizing anti-cancer drug-induced cardiotoxicity.

Adjuvant therapy with Jianpi Huayu decoction improves overall and recurrence-free survival after hepatectomy for hepatocellular carcinoma: a retrospective propensity score-matching study.

Hepatocellular carcinoma (HCC) patients experience high rates of recurrence following hepatectomy. Many herbal preparations used in traditional Chinese medicine have been shown to improve the postoperative condition of cancer patients. This retrospective study examined the efficacy and safety of Jianpi Huayu decoction (JPHYD) as adjuvant therapy for HCC following hepatectomy. HCC patients received postoperative management according to Chinese Society of Clinical Oncology recommendations, either alone (Control group) or in addition to daily JPHYD (1 week in hospital and 3 months after release). To reduce selection bias, we performed 1:1 propensity score matching between the Control and JPHYD groups. The main endpoint was recurrence-free survival (RFS), and secondary endpoints included overall survival (OS) and adverse event frequency. A total of 207 patients meeting inclusion criteria were enrolled, 127 in the Control group and 80 in the JPHYD group. Patients were then propensity score-matched, yielding each group of 80. Recurrence-free survival rate was significantly higher in the JPHYD group than in the Control group at 1 year (67.9% vs. 38.1%), 2 years (39.1% vs. 26.2%), and 3 years (31.3% vs. 26.2%) following hepatectomy (HR 0.5666 [95%CI, 0.3655 to 0.8784]; p = 0.0066). Additionally, OS was significantly higher in the JPHYD group than the Control group at 1 year (94.3% vs. 81.9%), 2 years (76.4% vs. 58.8%), and 3 years (66.3% vs. 51.4%) following hepatectomy (HR 0.5199 [95%CI, 0.2849 to 0.9490]; p = 0.027). Adverse events frequencies did not differ between the two groups. In conclusion, JPHYD can safely improve RFS and OS following hepatectomy for HCC.

Hepatectomy versus transcatheter arterial chemoembolization for resectable BCLC stage A/B hepatocellular carcinoma beyond Milan criteria: A randomized clinical trial.

Background: Hepatectomy is the recommended option for radical treatment of BCLC stage A/B hepatocellular carcinoma (HCC) that has progressed beyond the Milan criteria. This study evaluated the efficacy and safety of preoperative neoadjuvant transcatheter arterial chemoembolization (TACE) for these patients. Methods: In this prospective, randomized, open-label clinical study, BCLC stage A/B HCC patients beyond the Milan criteria were randomly assigned (1:1) to receive either neoadjuvant TACE prior to hepatectomy (NT group) or hepatectomy alone (OP group). The primary outcome was overall survival (OS), while the secondary outcomes were progression-free survival (PFS) and adverse events (AEs). Results: Of 249 patients screened, 164 meeting the inclusion criteria were randomly assigned to either the NT group (n = 82) or OP group (n = 82) and completed follow-up requirements. Overall survival was significantly greater in the NT group compared to the OP group at 1 year (97.2% vs. 82.4%), two years (88.4% vs. 60.4%), and three years (71.6% vs. 45.7%) (p = 0.0011) post-treatment. Similarly, PFS was significantly longer in the NT group than the OP group at 1 year (60.1% vs. 39.9%), 2 years (53.4% vs. 24.5%), and 3 years (42.2% vs. 24.5%) (p = 0.0003). No patients reported adverse events of grade 3 or above in either group. Conclusions: Neoadjuvant TACE prolongs the survival of BCLC stage A/B HCC patients beyond the Milan criteria without increasing severe adverse events frequency. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2200055618.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Epidemiology and prognostic analysis of patients with pancreatic signet ring cell carcinoma: a population-based study.

BACKGROUND: Pancreatic signet ring cell carcinoma (PSRCC) is a rare tumour subtype with poorly understood epidemiological characteristics and prognosis. We attempted to comprehensively characterise the epidemiology and survival outcomes of PSRCC. METHODS: Patients diagnosed with PSRCC between 2000 and 2018 were identified using Surveillance, Epidemiology and End Results Stat 8.3.9.2 software. Age-adjusted incidence and survival were calculated. Survival curves were plotted using the Kaplan-Meier method, and the differences between survival curves were compared using the log-rank test. Cox proportional hazards models were used to evaluate factors that independently predict overall survival. The primary analysis was a complete case analysis; multiple imputations were employed in a sensitivity analysis. RESULTS: We identified 585 eligible patients with PSRCC. The overall annual incidence from 2000 to 2018 was 0.349 (95% CI, 0.321-0.379) per million population. The incidence increased significantly in patients over 55 years of age and peaked at about 80 years of age (2.12 per million). Males and Black patients had the highest incidence. The observed survival rates at 1, 2 and 5 years were 20.1, 8.3 and 3.4%, respectively. Survival analysis revealed that primary surgery and chemotherapy are effective treatments for patients with PSRCC (P < 0.05). According to multivariate Cox regression analysis, early stage and receiving surgery and chemotherapy were favourable factors (P < 0.05). Similar conclusions were drawn from the interpolated data. CONCLUSIONS: PSRCC is a highly malignant tumour that predominates in elderly, male and Black patients. The prognosis is poor with a 5-year survival rate of 3.4%; however, multivariate analysis and adjusted models accounting for missing data revealed that early diagnosis, surgery and chemotherapy are effective in improving the prognosis.

The Prognostic Value of Serum Apolipoprotein A-I Level and Neutrophil-to-Lymphocyte Ratio in Colorectal Cancer Liver Metastasis.

Background: Colorectal cancer liver metastasis (CRLM) is a high degree of malignancy with rapid disease progression and has a poor prognosis. Both serum apolipoprotein A-I (ApoA-I) and neutrophil-to-lymphocyte ratio (NLR) play key roles in anti-inflammation and antitumor. This study is aimed at evaluating the implication of serum ApoA-I level in combination with NLR in the prognosis of CRLM. Methods: We retrospectively analyzed the serum ApoA-I level and NLR in 237 patients with CRLM. Cox regression analyses were used to identify the independent prognostic significance of these indicators. Kaplan-Meier method and Log-rank test were applied to compute overall survival (OS). Both the ApoA-I and NLR were divided into three levels, according to their medians. A risk-stratified prediction model was established to evaluate the prognosis of patients with CRLM. The ROC curve AUC values were applied to evaluate the capability of the model. Results: Higher levels of ApoA-I and lower NLR were strongly associated with prolonged OS (Log-rank test, P < 0.05). The patients were then grouped into three queues according to the ApoA-I level and NLR. There was a crucial diversity in the OS (P < 0.001) between the high-risk (ApoA - I ≤ 1.03 g/L and NLR > 3.24), medium-risk (ApoA - I > 1.03 g/L or NLR ≤ 3.24) and low-risk groups (ApoA - I > 1.03 g/L and NLR ≤ 3.24). The AUC value of the prediction model (AUC = 0.623, 95% CI: 0.557-0.639, P = 0.001) was higher than other individual indicators (including ApoA-I, NLR, cT classification, and cN classification). Additionally, the association of the prediction model and cTN classification (AUC = 0.715, 95% CI: 0.606-0.708, P < 0.001) was better than the model and cTN classification alone. Conclusion: The combination of ApoA-I level and NLR could be a prognostic indicator for CRLM.

Jianpi Huayu decoction inhibits the epithelial-mesenchymal transition of hepatocellular carcinoma cells by suppressing exosomal miR-23a-3p/Smad signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Huayu decoction (JHD) is a traditional Chinese medicinal preparation used to treat a variety of malignant tumors including HCC, although the underlying mechanism remains unknown. Exosomes in the tumor microenvironment mediate intercellular signaling among cancer cells, but precise contributions to hepatocellular carcinoma (HCC) progression are still elusive. AIM OF THE STUDY: In this work, the main objective was to examine the mechanisms underlying anti-tumor effects of JHD and the potential contributions of exosomal signaling. MATERIALS AND METHODS: LC-MS/MS was used for quality control of JDH preparation, while nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and western blotting were used for verification of exosomes. In vitro assays included CCK8, wound healing assay, transwell invasion assay, qRT-PCR and western blotting were performed to investigate the effects of JHD on HCC cells and the molecular mechanism. Furthermore, the effects of JHD on subcutaneous tumor model of nude mice were also determined. RESULTS: JHD inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cultured HCC cells. Further, exosomes isolated from EMT-induced HCC cells promoted the migration, invasion and EMT of other cultured HCC cells, while exosomes isolated from EMT-induced HCC cells after JHD treatment had little effect. In addition, JHD reduced the expression of exosomal miR-23a-3p in cultured HCC cells. miR-23a-3p was significantly up-regulated in tumor compared with that in adjacent non-cancerous tissues of patients with HCC. HCC patients with high miR-23a-3p expression had poor overall survival after hepatectomy. Meanwhile, miR-23a-3p enhanced HCC cell proliferation, EMT, and expression of Smad signaling proteins. More importantly, overexpression of miR-23a-3p can reverse the inhibition of EMT and Smad signaling pathway caused by JHD treatment. In vivo assays, treatment with JHD also reduced the growth of HCC-derived tumors in nude mice, reduced the expression of miR-23a-3p in serum exosomes and the level of EMT in tumor cells. CONCLUSIONS: the antitumor effects of JHD on HCC are mediated at least in part by inhibition of EMT due to downregulation of exosome-mediated intercellular miR-23a-3p transfer and subsequent blockade of Smad signaling. Disrupting this exosomal miR-23a-3p/Smad signaling pathway may be an effective treatment.

JPHYD Inhibits miR-21-5p/Smad7-Mediated Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells.

Background: Studies have shown that Jianpi Huayu Decoction (JPHYD) can inhibit the growth of hepatocellular carcinoma cells, but the mechanism of its effect was not clear at present. Methods: We assessed the effect of JPHYD using liver cancer cells as in vitro cell model and xenograft tumor as in vivo model. CCK8, EdU, wound-healing, and transwell assays were performed to assess the cell growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines HepG2 and MHCC97H. Western blot assay was performed to observe the protein level of E-cadherin, Smad7, N-cadherin, Snail, Smad3, Vimentin, and Zeb1. qRT-PCR assay was used to observe the expression of miR-21-5p in clinical liver cancer tissue samples and in HepG2 and MHCC97H cells. Animal tumorigenesis experiments and in vivo imaging experiments were performed to assess the results of in vitro experiments. Results: We found that JPHYD could inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells and JPHYD decreased the level of N-cadherin, Snail, Vimentin, Smad3, and Zeb1 and increased E-cadherin and Smad7 proteins. The expression of miR-21-5p was increased while that protein of Smad7 was decreased in HCC tissues. The vivo experiments also showed that miR-21-5p could promote the migration of HCC cells. JPHYD decreased miR-21-5p expression. The same results have been found in animal studies. Conclusion: Our results indicated that JPHYD inhibited epithelial-mesenchymal transition by increasing Smad7 expression and inhibiting miR-21-5p. Therefore, blocking the occurrence and development of EMT may be a new mechanism of JPHYD's anti-liver cancer effect.

CircFGGY Inhibits Cell Growth, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma via Regulating the miR-545-3p/Smad7 Axis.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Circular RNAs (circRNAs) play critical roles in the progression of HCC. However, the role of the newly identified circFGGY (hsa_circ_0006633) in the development and progression of HCC has not been explored. In this study, we found that circFGGY was significantly downregulated in tumor compared with that in adjacent normal liver tissues of patients with HCC. HCC patients with low circFGGY expression had poor overall survival after hepatectomy. Moreover, it was found that circFGGY could inhibit the proliferation, invasion and epithelial-mesenchymal transition of HCC both in vivo and in vitro. Mechanistically, circFGGY promoted the expression of Smad7, a well-known suppressor of the transforming growth factor-ß signaling pathway. In addition, miR-545-3p, a tumor promoter targeting both circFGGY and Smad7, suppressed the upregulation of Smad7 caused by circFGGY overexpression. Collectively, our data revealed that circFGGY inhibits the proliferation and invasion of HCC cells by sponging miR-545-3p and promote the expression of Smad7, indicating that circFGGY functions as a tumor suppressor and could be a prognostic biomarker for HCC.

Ferroptosis-related lncRNA signature predicts the prognosis and immune microenvironment of hepatocellular carcinoma.

This study aimed to construct a ferroptosis-related lncRNA signature to probe the prognosis and immune infiltration of HCC patients. The Cancer Genome Atlas (TCGA) database was randomly divided into two parts, with two-thirds training and one-third testing sets. Univariate, multivariate, and least absolute selection operator (LASSO) Cox regression analyses were performed to establish a ferroptosis-related lncRNA signature. The prognostic signature was constructed by 6 ferroptosis-related lncRNAs (PCAT6, MKLN1-AS, POLH-AS1, LINC00942, AL031985.3, LINC00942) shows a promising clinical prediction value in patients with HCC. Patients with high-risk score indicated a poorer prognosis than patients with low-risk score were shown in the training set (p < 0.001) and testing set (p = 0.024). Principal component analysis (PCA) and nomogram were performed to verify the value of the prognostic signature. The area under curves (AUCs) for 1-, 3-, and 5-year survival rates were 0.784, 0.726, 0.699, respectively. Moreover, TCGA revealed that immune cell subpopulations and related functions, including cytolytic activity, MHC class I, type I and type II IFN response, were significantly different between the two risk groups. Immune checkpoints such as PDCD1, CTLA4, CD44, VTCN1 were also abnormally expressed between the two risk groups. This prognostic signature based on the ferroptosis-related lncRNAs may be promising for the clinical prediction of prognosis and immunotherapeutic responses in patients with HCC.

AURKB, CHEK1 and NEK2 as the Potential Target Proteins of Scutellaria barbata on Hepatocellular Carcinoma: An Integrated Bioinformatics Analysis.

OBJECTIVE: We aim to explore the potential anti-HCC mechanism of Scutellaria barbata through integrated bioinformatics analysis. METHODS: We searched active ingredients and related targets of Scutellaria barbata via TCMSP database, PubChem and SwissTargetPrediction database. Then, we identified HCC disease targets from GEO dataset by WGCNA. Next, the intersected targets of disease targets and drug targets were input into STRING database to construct PPI networking in order to obtain potential therapeutic targets of Scutellaria barbata. Cytoscape software was used to carry out network topology analysis of potential targets. We used the R package for GO analysis and KEGG analysis. Finally, we used AutoDock vina and PyMOL software for molecular docking. RESULTS: Sixteen active components from Scutellaria barbata were lastly selected for further investigation. A total of 442 component targets were identified from 16 active ingredients of Scutellaria barbata after the removal of duplicate targets. GSE45436 was selected for construction of WGCNA and screening of differentially expressed genes. A total of 354 genes were up-regulated in HCC samples and 100 were down-regulated in HCC patients. Twenty-one common genes were obtained by intersection and 10 critical targets were filtered for further investigation. The enrichment analysis showed that cell cycle, DNA replication, p53 signaling pathway were mainly involved. The molecular docking results showed that 4 potential combinations were with the best binding energy and molecular interactions. CONCLUSION: AURKB, CHEK1 and NEK2 could be the potential target proteins of Scutellaria barbata in treating HCC. Cell cycle, DNA replication, p53 signaling pathway consist of the fundamental regulation cores in this mechanism.

Metastatic Colorectal Cancer Patient With Microsatellite Stability and BRAFV600E Mutation Showed a Complete Metabolic Response to PD-1 Blockade and Bevacizumab: A Case Report.

A vast majority of colorectal cancer (CRC) patients with microsatellite stability (MSS) or proficient mismatch repair (pMMR) are refractory to immunotherapeutic strategies. The current research focusses on the combined treatment strategies for identification and optimization in order to improve the efficacy of immunotherapy among patients with microsatellite stability (MSS), who account for the majority of metastatic colorectal cancer (mCRC) cases. mCRC patients harboring MSS and the BRAFV600E mutation show a worse prognosis and barely benefit from immunotherapy. In this report, we discuss the case of a mCRC patient with MSS and BRAFV600E mutation, who exhibited significant response to the combined treatment with nivolumab and bevacizumab, and has been exhibiting a progression-free survival (PFS) of more than 17 months. Our findings indicate that combined anti-angiogenic therapy can improve the efficacy of immunotherapy, which results in the prolong survival of the patient. This is a case report on MSS and BRAFV600E colorectal cancer which presents with a response to immunotherapy and anti-angiogenic therapy.

Xinyang Tablet inhibits MLK3-mediated pyroptosis to attenuate inflammation and cardiac dysfunction in pressure overload.

ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been traditionally used in the treatment of cardiovascular diseases (CVDs). Our previous study indicated that XYT exhibited protective effects in heart failure (HF). AIM OF THE STUDY: The aim of the present study was to determine the protective effects of XYT in pressure overload induced HF and to elucidate its underlying mechanisms of action. MATERIALS AND METHODS: We analyzed XYT content using high-performance liquid chromatography (HPLC.). Mice were subjected to transverse aortic constriction (TAC) to generate pressure overload-induced cardiac remodeling and were then orally administered XYT or URMC-099 for 1 week after the operation. HL1 mouse cardiomyoblasts were induced by lipopolysaccharides (LPS) to trigger pyroptosis and were then treated with XYT or URMC-099. We used echocardiography (ECG), hematoxylin and eosin (H&E) staining, Masson's trichrome staining and a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay to evaluate the effects of XYT. Messenger ribonucleic acid (mRNA) levels of collagen metabolism biomarkers and inflammation-related factors were detected. We determined protein levels of inflammation- and pyroptosis-related signaling pathway members via Western blot (WB). Caspase-1 activity was measured in cell lysate using a Caspase-1 Activity Assay Kit. Subsequently, to define the candidate ingredients in XYT that regulate mixed-lineage kinase-3 (MLK3), we used molecular docking (MD) to predict and evaluate binding affinity with MLK3. Finally, we screened 24 active potential compounds that regulate MLK3 via MD. RESULTS: ECG, H&E staining, Masson's trichrome staining and TUNEL assay results showed that XYT remarkably improved heart function, amelorated myocardial fibrosis and inhibited apoptosis in vivo. Moreover, it reduced expression of proteins or mRNAs related to collagen metabolism, including collagen type 1 (COL1), fibronectin (FN), alpha smooth-muscle actin (α-SMA), and matrix metalloproteinases-2 and -9 (MMP-2, MMP-9). XYT also inhibited inflammation and the induction of pyroptosis at an early stage, as well as attenuated inflammation and pyroptosis levels in vitro. CONCLUSION: Our data indicated that XYT exerted protective effects against pressure overload induced myocardial fibrosis (MF), which might be associated with the induction of pyroptosis-mediated MLK3 signaling.

Using Integrated Bioinformatics Analysis to Identify Abnormally Methylated Differentially Expressed Genes in Hepatocellular Carcinoma.

OBJECTIVE: For the identification of abnormally methylated differentially expressed genes (MDEGs) in hepatocellular carcinoma (HCC), this study integrated four microarray datasets to investigate the fundamental mechanisms of tumorigenesis. METHODS: We obtained the expression (GSE76427, GSE57957) and methylation (GSE89852, GSE54503) profiles from Gene Expression Omnibus (GEO). The abnormally MDEGs were identified by using R software. We used the clusterProfiler package for the functional and pathway enrichment analysis. The String database was used to build the protein-protein interaction (PPI) network and visualize it in Cytoscape. MCODE was employed in the module analysis. Additionally, Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) were employed to validate results. Lastly, we used cBioPortal software to examine the hub genetic alterations. RESULTS: We identified 162 hypermethylated, down-regulated genes and 190 hypomethylated, up-regulated genes. Up-regulated genes with low methylation were enriched in biological processes, such as keratinocyte proliferation, and calcium homeostasis. Pathway analysis was enriched in the AMPK and PI3K-Akt signaling pathways. The PPI network identified PTK2, VWF, and ITGA2 as hypomethylated, high-expressing hub genes. Down-regulated genes with high methylation were related to responses to peptide hormones and estradiol, multi-multicellular organism process. Pathway analysis indicated enrichment in camp, oxytocin signaling pathways. The PPI network identified CFTR, ESR1, and CXCL12 as hypermethylated, low-expressing hub genes. Upon verification in TCGA databases, we found that the expression and methylation statuses of the hub genes changed significantly, and it was consistent with our results. CONCLUSION: The novel abnormally MDEGs and pathways in HCC were identified. These results helped us further understand the molecular mechanisms underlying HCC invasion, metastasis, and development. Hub genes can serve as biomarkers for an accurate diagnosis and treatment of HCC, and PTK2, VWF, ITGA2, CFTR, ESR1, and CXCL12 are included.

The contemporary trend in worsening prognosis of pancreatic acinar cell carcinoma: A population-based study.

BACKGROUND: Primary acinar cell carcinoma (ACC) is a rare exocrine tumor of the pancreas with unclear clinical characteristics. Our goal was to determine the incidence and update the clinical characteristics and outcomes of ACC. METHODS: Through the Surveillance, Epidemiology, and End Results (SEER) database, we identified 252 patients with the latest diagnosis of ACC (2004-2016). The age-adjusted incidence (AAI) was calculated using the SEER*Stat Software version 8.3.6. The Kaplan-Meier method was used to draw survival curves and differences among them were compared by the log-rank test. Cox proportional hazards models were used to evaluate factors that had independent predictive effects on the overall survival. RESULTS: The AAI of pancreatic ACC was on the rise with the mean age at diagnosis of 63.79±14.79 years. Most patients (15.9%) had poorer differentiated tumors. The patients presented with distant stage were 54.4% compared with 53.1% between 1988 and 2003. The 1-, 2-, and 5-years survival rates for pancreatic ACC patients were 53.5%, 34.6%,17.5%, respectively (compared with 78.5%, 67.0%, and 42.8%, between 1988 and 2003). The multivariate COX analysis showed that the patient's age, surgery, chemotherapy, and summary stage, but not marital status were independent prognosis factors for ACC. CONCLUSIONS: Pancreatic ACC is a highly malignant tumor with an increasing incidence in recent years. The rate of distant metastasis is increasing and the survival rate is worse than in the past, suggesting that it may require more aggressive treatment and follow-up. Surgery, radiotherapy, and chemotherapy are all effective treatments, but prospective studies are still needed to verify them.

Treatment of syncope in tongue cancer with palliative chemotherapy in the intensive care unit: A case report.

RATIONALE: Syncope caused by head and neck cancer (HNC) is rare. However, syncope caused by tongue cancer (TC) is even rarer. In TC, syncope is caused by tumor-mediated compression of the carotid sinus and stimulation of the glossopharyngeal nerve. PATIENT CONCERNS: In this study, we report the case of a 48-year-old male patient who was diagnosed with advanced TC and bilateral cervical lymph node metastasis. On the third day of admission, the patient experienced recurrent syncope with hypotension and bradycardia. DIAGNOSES: The patient was diagnosed with a well-differentiated squamous cell carcinoma of the tongue along with massive cervical lymph node metastasis and carotid sinus syndrome. INTERVENTIONS: Initially, symptomatic treatment of syncope boosted the blood pressure and increased the heart rate. Thereafter, a temporary pacemaker was implanted. Finally, chemotherapy was used to control the tumor and relieve syncope. OUTCOMES: After chemotherapy, the tongue ulcers and cervical lymph node reduced in size; syncope did not recur. LESSONS: This case shows that chemotherapy may be a valid treatment option in patients with cancer-related syncope; however, the choice of chemotherapeutic drugs is critical. Intensive care provides life support to patients and creates opportunities for further treatment.