Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study.

BACKGROUND: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. METHODS: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m 2 docetaxel, 80 mg/m 2 oxaliplatin, 200 mg/m 2 calcium levofolinate, 2600 mg/m 2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9% (95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. CONCLUSIONS: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population.

POU2F1/DNMT3a Pathway Participates in Neuropathic Pain by Hypermethylation-Mediated LRFN4 Downregulation Following Oxaliplatin Treatment.

Evidence demonstrates that DNA methylation is associated with the occurrence and development of various neurological diseases. However, the potential target genes undergoing DNA methylation, as well as their involvement in the chemotherapy drug oxaliplatin-induced neuropathic pain, are still unclear. Here, Lrfn4, which showed hypermethylation in the promoter regions, was screened from the SRA methylation database (PRJNA587622) following oxaliplatin treatment. MeDIP and qPCR assays identified that oxaliplatin treatment increased the methylation in Lrfn4 promoter region and decreased the expression of LRFN4 in the spinal dorsal horn. The assays with gain and loss of LRFN4 function demonstrated that LRFN4 downregulation in spinal dorsal horn contributed to the oxaliplatin-induced mechanical allodynia and cold hyperalgesia. Moreover, oxaliplatin treatment increased the DNA methyltransferases DNMT3a expression and the interaction between DNMT3a and Lrfn4 promoter, while inhibition of DNMT3a prevented the downregulation of LRFN4a induced by oxaliplatin. We also observed that the transcriptional factor POU2F1 can bind to the predicted sites in DNMT3a promoter region, oxaliplatin treatment upregulated the expression of transcriptional factor POU2F1 in dorsal horn neurons. Intrathecal injection of POU2F1 siRNA prevented the DNMT3a upregulation and the LRFN4 downregulation induced by oxaliplatin. Additionally, intrathecal injection of DNMT3a siRNA or POU2F1 siRNA alleviated the mechanical allodynia induced by oxaliplatin. These findings suggested that transcription factor POU2F1 upregulated the expression of DNMT3a, which subsequently decreased LRFN4 expression through hypermethylation modification in spinal dorsal horn, thereby mediating neuropathic pain following oxaliplatin treatment.

A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma.

BACKGROUND: Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC. METHODS: In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1-14, 135 mg/m2 intravenous paclitaxel on day 1, and 60-75 mg/m2 intravenous cisplatin on days 1-3 every 3 weeks for a maximum of 4-6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30-19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2-87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2-97.6%). The median duration of response was 6.80 months (95% CI, 4.52-9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002-0.606; P = 0.022). CONCLUSIONS: The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04063683. Registered 21 August 2019.

Single-cell transcriptome sequencing reveals potential novel combination of biomarkers for antibody-based cancer therapeutics in hepatocellular carcinoma.

Background: Antibody-based cancer therapeutics is developing rapidly in recent years for its advantages in precisely targeting the tumor cells. However, tumor-specific cell surface antigens are still lacking, and the heterogeneity of tumor mass greatly impeded the development of effective drugs. Methods: In the present study, single-cell RNA sequencing was used to dissect tumor heterogeneity in human hepatocellular carcinoma (HCC). Tissues from different spatial regions including the tumor, para-tumor, and distant normal liver tissues were dissociated into single cells, and the gene expressions were compared in a different subpopulation of cells from these regions and validated in independent cohorts. Results: A total of 28 cell clusters with different distribution patterns and gene expression profiles were identified within a heterogenous tumor and its paired liver tissues. Differentially expressed genes encoding the plasma membrane in cells with hepatic lineage were further extracted from single-cell transcriptome sequencing and validated in TCGA database. A 3-gene signature was identified to be significantly upregulated in dominant HCC tumor cell subpopulations with prognostic significance and validated in multiple independent patient cohorts. Conclusion: The composition of the three plasma membrane proteins on the surface of HCC tumor cells within a heterogenous tumor might indicate poor prognostic tumor subpopulations during cancer evolution and potential therapeutic targets.

Exosomal microRNA-155 as a biomarker for hepatic fibrosis diagnosis and progression.

BACKGROUND: Pathological examination of liver biopsies remains the gold standard for evaluating the stage of hepatic fibrosis, which are a number of disadvantages associated with biopsy. The aim of the present study was to investigate the potential of exosomal microRNA (miR)-155 as a non-invasive biomarker for the diagnosis and progression of hepatic fibrosis. METHODS: Exosomal miR-155 quantity was analyzed by sampling serum exosomes of patients with hepatic fibrosis and a hepatic fibrosis rat model. A total of 94 patients were divided into three groups based on Child-Pugh rating. Additionally, 30 patients with primary liver fibrosis who underwent liver transplantation were divided into the low miR-155 expression group and the high expression group; 56 rats were divided into 7 groups (n=8, 0, 2, 4, 6, 8, 10, and 12 weeks). Rats in every group were intravenously injected with CCl4 (3% vol/vol in olive oil; 0.3 mL/100 g body weight) twice weekly to produce different degrees of liver necrosis and liver fibrosis. RESULTS: Exosomal miR-155 was found to be closely associated with the progression of cirrhosis and clinical prognostic indicators of cirrhosis. Exosomal miR-155 gradually increased with the severity of hepatic necrosis and fibrosis. CONCLUSIONS: The findings of the present study indicate that exosomal miR-155 can act as a non-invasive biomarker for the diagnosis and progression of hepatic fibrosis.

Surgical outcomes and survival for T4 gastric cancer extending to the transverse colon.

BACKGROUND: For the treatment of locally advanced (T4) gastric cancer, extended multi-organ resection remains controversial. This study aimed to evaluate the surgical outcomes and survival of patients with T4 gastric cancer extending to the transverse colon. METHODS: A total of 2,652 gastric cancer patients underwent surgery between December 2011 and December 2015. Data from 40 of these patients who underwent curative resection for T4 gastric cancer extending to the transverse colon were obtained. Patient characteristics, related complications, long-term survival, and prognostic factors for T4 gastric cancer were analyzed. RESULTS: Postoperative morbidity occurred in 5 (12.5%) patients. All of the patients were cured with conservative treatment. No procedure-related mortality occurred. The 1-, 3-, and 5-year overall survival (OS) rates were 75.0%, 49.2%, and 36.9%, respectively, with a median survival time of 24 months. Univariate analysis revealed tumor size (P=0.049), advanced T stage (P=0.013), and lymph node metastasis (P=0.006) to be poor prognostic factors of OS. Advanced T stage and lymph node metastasis were identified by multivariate analysis as being independent prognostic factors. Further, it was observed that lymph node metastasis grade was associated with poorer OS. CONCLUSIONS: Patients with T4 gastric cancer extending to the transverse colon might benefit from curative resection with acceptable morbidity and mortality.

Serum miR-191 and miR-425 as Diagnostic and Prognostic Markers of Advanced Gastric Cancer Can Predict the Sensitivity of FOLFOX Chemotherapy Regimen.

PURPOSE: miR-191 and miR-425 have been proved to be highly expressed in gastric carcinoma (GC). However, little research has been done on their clinical value in serum of patients with advanced GC. In addition, it is not clear whether they can be used as markers for the response and prognosis of GC patients treated with oxaliplatin combined with 5-fluorouracil and FOLFOX chemotherapy. PATIENTS AND METHODS: A total of 230 patients with advanced GC admitted to our hospital were selected as the study objects, all of whom received FOLFOX chemotherapy regimen. Another 100 cases of healthy subjects were included. QRT-PCR was employed to detect the serum expression of miR-191 and miR-425 in patients. RESULTS: Compared with the healthy subjects, the serum expressions of miR-191 and miR-425 in GC patients were significantly upregulated, which were correlated with differentiation degree and TNM staging, respectively. According to the ROC curve, the AUC of miR-191 and miR-425 for GC diagnosis was 0.937 and 0.901, respectively, while the AUC for differentiation degree diagnosis was 0.854 and 0.822, and that for TNM staging diagnosis was 0.860 and 0.829, respectively. The predictive AUC of miR-191 and miR-425 for chemosensitivity was 0.868 and 0.835, respectively, with a combined predictive AUC of 0.935. Low differentiation degree, high TNM staging, high miR-191 and high miR-425 expressions were independent risk factors for chemotherapy insensitivity. Differentiation degree, TNM staging, chemotherapy effect, miR-191 and miR-425 were independent influencing factors for the prognosis of GC patients. CONCLUSION: Up-regulated expression of miR-191 and miR-425 in the serum of patients with advanced GC are effective biomarkers for the diagnosis, chemotherapy and prognosis evaluation of GC.

Survey and analysis of the nutritional status in hospitalized patients with malignant gastric tumors and its influence on the quality of life.

BACKGROUND/OBJECTIVES: The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients' quality of life (QOL). METHODS: We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. RESULTS: By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01). CONCLUSION: Malnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients' quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.

Evaluation of PAX8 expression promotes the proliferation of stomach Cancer cells.

BACKGROUND: PAX8 was not only a mitotic factor, but identified as a transcription factor involved in the prognosis of human tumor patients. Elucidating the function of PAX8 on the pathology of stomach cancer was meaningful. RESULTS: PAX8 was found to be upregulated in primary stomach cancer tissue and the TCGA stomach cancer dataset. Interestingly, SOX13 and PAX8 showed consistent expression patterns, and the combined high PAX8 and SOX18 expression induced a worse prognosis of stomach cancer patients. SOX13 was further identified as a transcription factor of PAX8, and further affect Aurora B and Cyclin B1 expression, two cell cycle related factors of the downstream of PAX8, including. Furthermore, PAX8 depletion inducted G1-phase arrest and the decrease of EdU incorporation, cell viability and colony formation can be rescued by SOX13 overexpression. CONCLUSIONS: SOX13 participated in the elevated expression of PAX8, which promote the proliferation of stomach cancer cells. Therefore, SOX13 mediated PAX8 expression was recognized as a tumor-promoting role in stomach cancer.

SOX13 dependent PAX8 expression promotes the proliferation of gastric carcinoma cells.

PAX8 is identified as a regulator in the pathogenesis of human tumours and an indicator of the prognosis for patients. However, the role of PAX8 on proliferation in gastric cancer have not been studied. This study was aimed to explore the expression pattern of PAX8 in gastric cancer, and investigate the effect of PAX8 on the proliferation of gastric cancer cells. PAX8 and SOX13 were identified to be synchronously up-regulated in primary gastric cancer in human gastric cancer tissues and the gastric cancer datasets of TCGA, and gastric cancer patients of combined high PAX8 and SOX13 expression showed poor prognosis. Furthermore, SOX13 can mediate PAX8 and its targeted genes, Aurora B and Cyclin B1, expression in AGS and MGC803 cell lines. Flow cytometry and EdU incorporation assays showed that silencing PAX8 can block the cell cycle of gastric cancer cell in G1 phase and SOX13 expression can rescue the arrested proliferative process induced by PAX8 silenced in CCK8 and colony formation assays. Thus, combined SOX13 and PAX8 expression regulate the proliferation of gastric cancer cells, and both SOX13 and PAX8 play an oncogene function in gastric cancer.

Short-term impact of breast cancer screening intervention on health-related quality of life in China: A multicentre cross-sectional survey.

OBJECTIVE: The impact of participating in breast cancer screening programmes on health-related quality of life (HRQoL)is poorly understood. METHODS: Based on a national breast cancer screening programme in China, a multicentre cross-sectional survey was conducted covering 12 provinces from September 2013 to December 2014. HRQoL of participants in the screening population and general population was evaluated by the three-levelEuroQol-five-Dimensions (EQ-5D-3L) instrument, and utility scores were generated through the Chinese value set. Univariate and multivariate regression analyses were performed to explore determinants of utility scores and anxiety/depression problems. RESULTS: For screening group and general population (n = 4756, mean age = 51.6 year old), the corresponding utility scores were 0.937 (95% CI, 0.933-0.941) and 0.953 (0.949-0.957) (P < .001). Pain/discomfort and anxiety/depression were the most common reported in both groups (51.4% and 34.3%, P < .001). Utility scores at prescreening, in-screening, and postscreening interview timings were 0.928 (0.921-0.935), 0.958 (0.948-0.969), and 0.938 (0.933-0.943), respectively (P < .001); the corresponding proportions of anxiety/depression reporting were 25.9%, 16.3%, and 21.1%, respectively (P = .004). Interview timing, geographical region, and insurance status were associated with HRQoL and anxiety/depression in women at high-risk of breast cancer. CONCLUSIONS: Utility scores of screening participants were significantly lower than that of general population in China, but the difference may be clinically insignificant. Further cohort studies using HRQoL measurements are needed.

Analysis of cyclin E co-expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer.

OBJECTIVE: To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. METHODS: The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan-Meier survival curve analysis. RESULTS: After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors' clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression (P < 0.05). CONCLUSIONS: NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.

Relationships among KRAS mutation status, expression of RAS pathway signaling molecules, and clinicopathological features and prognosis of patients with colorectal cancer.

BACKGROUND: The RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways all belong to mitogen-activated protein kinase (MAPK) signaling pathways, Mutations in any one of the upstream genes (such as the RAS gene or the BRAF gene) may be transmitted to the protein through transcription or translation, resulting in abnormal activation of the signaling pathway. This study investigated the relationship between the KRAS gene mutation and the clinicopathological features and prognosis of colorectal cancer (CRC), and the effect of KRAS mutations on its associated proteins in CRC, with an aim to clarify the cause of tumor progression and drug resistance caused by mutation of the KRAS gene. AIM: To investigate the KRAS gene and RAS pathway signaling molecules in CRC and to analyze their relationship with clinicopathological features and prognosis. METHODS: Colorectal cancer tissue specimens from 196 patients were analyzed for KRAS mutations using quantitative polymerase chain reaction and for KRAS, BRAF, MEK, and ERK protein expression levels using immunohistochemistry of tumor microarrays. To analyze differences of RAS pathway signaling molecule expression levels in different KRAS gene status, the relationships between these parameters and clinicopathological features, 4-year progression-free survival, and overall survival were analyzed by independent sample t test, Kaplan-Meier plots, and the log-rank test. Predictors of overall and disease-free survival were assessed using a Cox proportional hazards model. RESULTS: Of the 196 patients, 62 (32%) carried mutations in codon 12 (53/62) or codon 13 (9/62) in exon 2 of the KRAS gene. KRAS, BRAF, ERK, and MEK protein expression was detected in 71.4%, 78.8%, 64.3%, and 50.8% of CRC tissues, respectively. There were no significant differences between KRAS mutation status and KRAS, BRAF, MEK, or ERK protein levels. Positive expression of KRAS and ERK was associated with poor tumor differentiation, and KRAS expression was also associated with age < 56 years. MEK expression was significantly associated with distant metastasis (P < 0.05). The 4-year progression-free survival rate, but not overall survival rate, was significantly higher in patients with KRAS-negative tumors than in those with KRAS-positive tumors (P < 0.05), whereas BRAF, MEK, and ERK expression was unrelated to survival. Multivariate analysis showed that only the expression of KRAS protein was a risk factor for tumor recurrence (P < 0.05). No other clinicopathological factors correlated with KRAS, BRAF, MEK, or ERK expression. CONCLUSION: KRAS gene mutations do not affect downstream protein expression in CRC. KRAS protein is associated with poor tumor differentiation, older age, and a risk of tumor recurrence.

Non-Coding RNA Pvt1 Promotes Cancer Stem Cell-Like Traits in Nasopharyngeal Cancer via Inhibiting miR-1207.

Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant tumor. lncRNA-PVT1 can promote the proliferation of carcinoma cells, and induce cells to have stem cell-like potentials. However, the function of PVT1 in NPC cells is not clear. The expressions of lncRNA-PVT1 and the expressions of the stem cell markers in NPC tissues or cell lines were investigated by qRT-PCR or western blot. The cell proliferation, and the ability of NPC cells to form spherical, clonal colonies were investigated by MTT assay, colony formation assay, and tumor-sphere formation assay. Cancer stem cells surface markers were detected by flow cytometry and western blot. PI3K/AKT signal activation in NPC cells was determined by western blot. PVT1 was significantly up-regulated in both NPC tissues and cell lines and associated with poor prognosis. PVT1 knockdown reduced NPC cells viability, clonogenicity, the cell surface CD44+/CD24- stem phenotype, and the expressions of the stem cell markers in NPC cells, including Oct4, c-Myc, SOX2, and ALDH. Furthermore, PVT1 negatively regulates the expression levels of miR-1207 in NPC cells and spheres cells, which is critical for NPC stemness. Knockdown of miR-1207 promoted stem phenotype and the expressions of the stem cell markers in NPC cells. Moreover, phosphor-PI3K (p-PI3K) and phosphor-AKT (p-AKT) were found to be down-regulated after PVT1 siRNAs transfection in NPC cells. And miR-1207 inhibitor transfection reversed the all the effects brought by PVT1 knockdown. Pvt1 promotes cancer stem cell-like properties in NPC cells via inhibiting miR-1207 and activating the PI3K/AKT signal pathway.

Incidence and mortality of liver cancer in Henan province in 2015.

OBJECTIVE: Liver cancer is one of the most common types of cancer. We aimed to use the cancer registration data in 2015 to estimate the incidence and mortality of liver cancer in Henan province. METHODS: The data from 37 population-based cancer registries in Henan province were collected for this study. The pooled data were stratified by area, sex, and age group. New cases of liver cancer and deaths due to the disease were estimated using age-specific rates and provincial population in 2015. All incidence and death rates were age standardized to the 2000 Chinese standard population and Segi's population, which were expressed per 100,000 populations. RESULTS: After clearance and assessment, data from 30 population-based cancer registries (5 in urban and 25 in rural areas) were included in the analysis. All 30 cancer registries encompassed a total population of 23,421,609 (3,507,984 in urban and 19,913,625 in rural areas), accounting for 21.84% of the provincial population. The proportion of morphological verification (MV%), percentage of cancer cases identified with death certification only (DCO%), and mortality-to-incidence ratio (M/I) were 38.55%, 2.34%, and 0.81, respectively. Approximately 31,639 new cases of liver cancer were diagnosed and 26,057 deaths from liver cancer occurred in Henan in 2015. The crude incidence rate of liver cancer was 27.05/100,000 (36.24/100,000 in men and 17.35/100,000 in women). Age-standardized incidence rates by Chinese standard population and world standard population were 21.10/100,000 and 20.95/100,000, respectively. Liver cancer was more common in men than in women. The incidence rates in urban (26.31/100,000) and rural (27.18/100,000) areas were similar. The crude mortality rate of liver cancer was 21.98/100,000 (29.33/100,000 in males and 14.22/100,000 in females). Age-standardized mortality rates by Chinese standard population and world standard population were 16.93/100,000 and 16.90/100,000, respectively. There was no distinct difference in mortality rates of liver cancer between urban (22.55/100,000) and rural (21.87/100,000) areas. CONCLUSIONS: Liver cancer has posed a heavy burden on people in Henan province. Comprehensive measures should be conducted to prevent the increase in the incidence of liver cancer.

Comparison of the Efficacy and Prognostic Factors of Transarterial Chemoembolization Plus Microwave Ablation versus Transarterial Chemoembolization Alone in Patients with a Large Solitary or Multinodular Hepatocellular Carcinomas.

Objective: To evaluate the efficacy and prognostic factors associated with transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA) versus TACE alone for a large solitary or multinodular hepatocellular carcinomas (HCCs). Materials and Methods: This retrospective study involved 258 patients with a large solitary or multinodular HCCs (not more than 10 tumors) who underwent TACE + MWA (n = 92) or TACE alone (n = 166) between July 2011 and April 2015. Local tumor control, survival outcomes, and complications were compared between the two groups. Prognostic factors for time to progression (TTP) and overall survival (OS) were evaluated by univariate and multivariate analyses. Results: The median duration of follow-up was 21.2 months (range, 4-45 months). The median TTP and OS were 12.5 months and 26.6 months, respectively, for the TACE + MWA group and 6.7 months and 17.1 months, respectively, for the TACE group (p < 0.001). The 1-, 2-, and 3-year OS rates were 85.9, 59.8, and 32.6%, respectively, for the TACE + MWA group and 59.0, 40.4, and 11.4%, respectively, for the TACE group (p < 0.001). The corresponding recurrence rates were 47.8, 78.3, and 94.6% for the TACE + MWA group, respectively, and 74.7, 96.4, and 97.6%, respectively, for the TACE group (p < 0.001). Logistic regression analyses showed that the treatment method, tumor size, and tumor number were significant prognostic factors for TTP and OS. Conclusion: TACE + MWA appears to have more advantages compared to TACE in prolonging OS, with a satisfactory TTP, for inpatients with solitary large or multinodular HCCs. Treatment method, tumor size, and tumor number are significant prognostic factors for TTP and OS. Further randomized, multi-center, prospective trials are required to confirm the findings of this study.

High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression.

Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.

A retrospective clinical study of comparing paclitaxel plus S-1 versus paclitaxel plus cisplatin as the first-line treatment for patients with advanced esophageal squamous cell carcinoma.

BACKGROUND: In advanced esophageal squamous cell carcinoma (ESCC), paclitaxel plus cisplatin are considered as active and tolerable. The current clinical study was conducted to retrospectively compare the efficacy and safety of first-line paclitaxel/S-1(PS) and paclitaxel/cisplatin(TP) regimens in advanced ESCC. RESULTS: The overall response rate of PS was slightly, but not significantly, higher (25 patients, 46%) than that of TP (23 patients, 39%, P = 0.432). Median overall survival (OS) was similar for PS and TP (11.5 months vs. 10.4 months, p = 0.37). However PS had longer median progression-free survival than TP (PFS: 5.5 months vs5.0months, p = 0.04). When compared with PS, more grade 3 or 4 adverse events were recorded for TP, including leukopenia, neutropenia, anemia, anorexia and vomiting (P < 0.05). No treatment-related deaths were recorded in either group. PATIENTS AND METHODS: Between 2008 and 2014, all patients diagnosed with advanced ESCC and treated with paclitaxel/S-1 or paclitaxel/cisplatin at Cancer Hospital Affiliated to Zhengzhou University were analyzed retrospectively. One hundred and thirteen patients were included in this study. Disease control rates and progression-free survival (PFS) and overall survival (OS) were recorded. Survival analysis was calculated by using Kaplan-Meier method. CONCLUSIONS: The PS option improves PFS and its OS is similar to TP. Moreover, the PS regimen is an effective and safe first-line treatment for ESCC with less hematological and non-hematological toxicity.

Decreased expression of miR-542-3p exerts growth inhibitory functions in esophageal cancer.

OBJECTIVE: Identification of novel biomarkers and related molecular pathways are critical for understanding the underlying biology of human malignancies, as well as to design effective cancer therapeutics. MicroRNAs (miRNAs) are classified as a kind of short non-coding RNAs that interfere with specific target mRNAs and therefore regulate multiple biological processes. We characterized here the expression and function of miR-542-3p in esophageal squamous cell carcinoma (ESCC). METHODS: Real-time PCR was used to examine the miR-542-3p expression. After transfections of its synthetical mimics or inhibitor, cell growth rate was explored by cell counting assay. In addition, its expression was further statistically analyzed to reveal its association with clinical characters. RESULTS: We show that miR-542-3p, a well-characterized tumor suppressor was significantly decreased in ESCC tissues and cell lines, whose downregulation is tightly associated with tumor grade. Furthermore, forced expression of miR-542-3p suppressed cell proliferation, while silencing its expression by a synthetical inhibitor could enhance cell growth rate. CONCLUSION: Taken together, our results indicated that miR-542-3p is a tumor suppressor of esophageal cancer acting at steps that regulate cell growth.