[Evaluation for preparation and anticancer efficacy in vitro of drug-loaded nanoerythrosomes].

The objective of this study is to develop a new-type biodegradable, biocompatible curcumin-loaded nanoerythrosomes (Cur-RBC-NPs) by means of the sonication method. The size of Cur-RBC-NPs was optimized by varying drug loading parameters. The morphology, size distribution, stability, in vitro release pattern, cellular uptake of nanoparticles and in vitro anti-tumor effects were evaluated, respectively. The results showed the prepared Cur-RBC-NPs were nearly uniform spheres, with an average diameter of (245.7 ± 1.3) nm. Encapsulation efficiency (EE) and load efficiency (LE) of Cur-RBC-NPs were 50.65% ± 1.36% and 6.27% ± 0.29%. And the nanoparticles had a good sustained release property. According to the in vitro experiment, Cur-RBC-NPs were effectively taken in by tumor cells, and exhibited a significant anti-tumor effect. In conclusion, the method for preparing Cur-RBC-NPs is convenient, with a good sustained release behavior and anti-tumor efficacy, and so expected to be a new-type nano-drug delivery system in clinical practice.

Circulating tumour cells predict survival in gastric cancer patients: a meta-analysis.

AIM OF THE STUDY: The prognostic value of the detection of circulating tumour cells (CTCs) in gastric cancer has been studied intensely in recent years. However, the application of different technologies led to inconsistent results between the studies. Here, we performed a meta-analysis of published studies to summarise the evidence. MATERIAL AND METHODS: Medline and ISI Web of Knowledge were searched up to March 2013 using "circulating tumor cells" and "gastric cancer" as search terms. Hazard ratio (HR) with 95% confidence intervals (CIs) for prognostic outcomes and clinical characteristics were extracted from each study. Pooled hazard ratios (HR) and odds ratios (OR) were calculated using random or fixed-effects models. RESULTS: Twelve studies enrolling 774 patients were included. The combined HR estimate for overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were 1.41 (95% CI: 1.28-1.62), 2.99 (95% CI: 2.01-4.45) and 1.64 (95% CI: 1.02-2.62), respectively. Subgroup analysis concerning detection methods and sampling time showed that results of RT-PCR for the OS group and RT-PCR for the DFS group suggest a prognostic significance of CTC detection (pooled HR [95% CI]: 1.45 [1.28-1.65], I(2) = 38%, p = 0.13; 2.99 [2.01-4.45], I(2) = 0%, p = 0.32). In addition, results of the baseline CTC detection group also indicated a significant prognostic value to predict OS and DFS (pooled HR [95% CI]: 1.47 [1.19-1.82], I(2) = 38%, p = 0.14; 2.99 [2.01-4.45], I(2) = 0%, p = 0.32). We simultaneously found that the detection of CTCs correlated with pathological stage (pooled OR [95% CI]: 2.95 [1.65-5.28], I(2) = 56%, p = 0.03), lymph node status (pooled OR [95% CI]: 2.26 [1.50-3.41], I(2) = 37%, p = 0.09), the depth of invasion (pooled OR [95% CI]: 3.21 [1.38-7.43], I(2) = 72%, p = 0.002), and distant metastasis (pooled OR [95% CI]: 2.68 [1.25-5.73], I(2) = 43%, p = 0.15). CONCLUSIONS: Detection of CTCs is associated with poorer prognosis in gastric cancer patients.

[Generation and comparison of two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer].

OBJECTIVE: To generate two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer and to compare their biological properties. METHODS: The genetically engineered mice previously developed with mouse mammary tumor virus (MMTV) promoter driven expression of activated ErbB2/Neu and recombinant Cre (FVB/N-MMTV-NIC) were interbred with Flox-PTEN mice; and FVB/N-ErbB2KI mice, harboring endogenous promoter driven activated ErbB2/Neu expression, FVB/N-MMTV-Cre mice and the flox-PTEN mice were interbred. Neu, Cre and PTEN genes were amplified by PCR for genotyping of the offsprings. ErbB2/Neu and PTEN expression in mammary tumors were detected by immunohistochemistry. Tumor formation time, tumor number, histopathology and lung metastasis were compared between two models, Ki-67 expression was detected by immunohistochemistry, and TUNEL staining of tumor tissues was performed. RESULTS: Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer were generated. The models were confirmed by genotyping and immunohistochemistry. One model with exogenous MMTV promoter driven expression of activated ErbB2/Neu and Cre coupling PTEN disruption was designated as NIC/PTEN(-/-) mice, and the other with MMTV-Cre induced endogenous promoter driven expression of activated ErbB2/Neu with PTEN disruption was designated as ErbB2KI/PTEN(-/-) mice. The tumor formation time in NIC/PTEN(-/-) mice was significantly shorter than that of ErbB2KI/PTEN(-/-) mice (30 vs 368 d, P<0.01); the number of tumor and incidence of lung metastasis was also significantly higher in NIC/PTEN(-/-) mice (10 vs 1-2 and 75.0% vs 37.5%, respectively, Ps<0.01). The Two models displayed distinct histopathological morphology. NIC/PTEN(-/-) tumor showed more Ki-67 positive cells than ErbB2KI/PTEN(-/-) tumor did (86.9%±2.8% vs 37.4%±7.2%, P<0.01), while the amount of cell apoptosis in tumors was not significantly different between two models. CONCLUSION: Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer with different phenotypes have been successfully generated, which may provide useful resource for further investigation of the initiation and progression of HER2/ErbB2 breast cancer, as well as for the development of novel prevention and treatment regimens of this malignance.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023.

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

[Correlation between the methylation of SULF2 and WRN promoter and chemosensitivity to irinotecan in gastric cancer].

OBJECTIVE: To explore the relationship between SULF2 and WRN promoter methylation and chemosensitivity to irinotecan, and also the clinicopathological features in patients with gastric cancer. METHODS: The chemosensitivity to irinotecan was tested by MTT assay. The methylation of SULF2 and WRN promoter in the fresh gastric cancer tissues was detected by methylation specific PCR. The differences of chemosensitivity and clinicopathological features of the methylation group were compared with that of the non-methylation group. The tumor growth in nude mice bearing human gastric cancer xenografts treated with CPT-11was also observed. RESULTS: The methylation rates of SULF2 and WRN were 28.4% (29/102) and 23.5% (24/102), respectively. There were no significant association between promoter methylation and clinicopathological features of patients including age, gender, histologic type, lymphatic invasion, and TNM Stage. In all the 102 cases, there were 30 cases of irrinotecan-sensitive group, and 72 cases of the irrinotecan-resistant group. The SULF2 methylation rate was 46.7% (14/30)in the sensitive group, and 20.8% (15/72) in the resistant group (P = 0.008),The WRN methylation rate was 33.3% (10/30) in the sensitive group, and 19.4% (14/72) in the resistant group (P = 0.214). Gastric cancer tissues were more sensitive to irrinotecan when both the genes were methylated. The nude mice bearing human gastric cancer xenografts with SULF2 methylation were more sensitive to irrinotecan. CONCLUSIONS: The detection of SULF2 and WRN promoter methylation may provide evidence for screening and targeting the most sensitive gastric cancer subpopulation suitable for personalized irrinotecan chemotherapy.

Metarhizium anisopliae is a valuable grist for biocontrol in beta-cypermethrin-resistant Blattella germanica (L.).

BACKGROUND: The widespread use of chemical insecticides has resulted in the development of resistance in German cockroaches worldwide, and biopesticides based on entomopathogenic fungi as active ingredients have become a promising alternative strategy. Resistance can change many of the physiological and biochemical characteristics of insect pests, such as cuticle thickness, detoxification enzyme activity, and even intestinal flora composition. Thus, potential interactions between pathogenic fungi and insecticide resistance may lead to unpredictable changes in pest susceptibility to fungi. RESULTS: Beta-cypermethrin-resistant German cockroaches were more susceptible to infection with the fungus Metarhizium anisopliae regardless of age and sex. Histopathological results showed that the infection of resistant strains (R) by M. anisopliae was visibly faster than that of susceptible strains (S). The gut microbiota of the S strain indicated a stronger ability to inhibit fungi in vitro. The abundance of Parabacteroides, Lachnoclostridium, and Tyzzerella_3 decreased significantly in the R strain, and most demonstrated the ability to regulate glucose and lipid metabolism, and antifungal infections. The expression levels of Akirin, BgTPS, and BgPo genes in the R strain were significantly lower than those in the S strain, while BgChi and CYP4G19 gene expression were significantly higher. The mortality of cockroaches infected with M. anisopliae decreased to varying degrees after RNA interference, reflecting the role of these genes in antifungal infection. CONCLUSIONS: Results confirmed that insecticide resistance may enhance cockroach susceptibility to fungi by altering intestinal flora and gene expression. Fungal biopesticides have high utilization value in pest control and insecticide resistance management strategies. © 2021 Society of Chemical Industry.

[Relationship between BRCA1 mRNA expression in tumor cells from malignant effusions and chemosensitivity to cisplatin in patients with metastatic malignant effusions].

OBJECTIVE: To explore the mRNA expression of breast cancer susceptibility gene 1 (BRCA1) in tumor cells isolated from malignant pleural and peritoneal effusions, and the predictive role of BRCA1 related to the efficacy of cisplatin-based chemotherapy. METHODS: Tumor cells were isolated from malignant pleural and peritoneal effusions of 31 cancer patients. The response of these tumor cells to cisplatin was determined by CCK8 assay. Real time quantitative RT-PCR was used to examine the BRCA1 mRNA level in the primary culture cancer cells. RESULTS: The expression level of BRCA1 mRNA was 0.618 (0.014 - 18.063) in primary culture tumor cells. The IC(50) of DDP was 2.809 µg/ml in the primary culture tumor cells (0.118 - 19.439 µg/ml). Both BRCA1 mRNA expression and the tumor cells IC(50) of DDP were not significantly related with patient age, gender, the type of primary tumor, whether to accept the chemotherapy and effusion type (P > 0.05). The level of BRCA1 mRNA was negatively correlated with the chemosensitivity in terms of IC(50) of cisplatin (P < 0.001). CONCLUSION: Assessment of expression level of BRCA1 mRNA may be useful in predicting the efficacy of cisplatin-based chemotherapy in patients with metastatic malignant effusions.

[Predictive values of platinum-related gene polymorphisms in gastric cancer patients on oxaliplatin-based adjuvant chemotherapy].

OBJECTIVE: To explore the predictive values of platinum-related genes in gastric cancer patients on oxaliplatin-based adjuvant chemotherapy. METHODS: A total of 126 gastric cancer patients received at least 6 cycles of modified FOLFOX4 adjuvant chemotherapy. Single nuclear polymorphisms (SNPs) in ERCC1 Asp118Asp, XRCC1 Arg399Gln, XPD Lys751Gln and GSTP1 Ile105Val were assessed with 5' nuclease allelic discrimination assay (TaqMan) by real-time polymerase chain reaction and direct sequencing. The genotypes were tested for an association with survivals in gastric cancer patients on an oxaliplatin-based adjuvant chemotherapy regimen. RESULTS: The genotypic analysis of all patients indicated the frequencies for the homozygous wild-type allele, heterozygous and homozygous polymorphic variant: 64.29%, 28.57% and 7.14% for ERCC1-118; 56.35%, 38.89% and 4.76% for XRCC1-399; 84.92%, 15.08% and 0 for XPD-751; and 68.25%, 30.60% and 3.97% for GSTP1-105. Univariate analysis indicated that the ERCC1-118, the XRCC1-399 and the GSTP1-105 SNPs showed the predictive values for RFS (relapse-free survival) (P<0.001, P=0.001 and P<0.001 respectively) and OS (overall survival) (P<0.001, P=0.001 and P=0.019 respectively). A multivariable analysis of Cox proportional hazard regression model suggested that ERCC1-118 had a significant predictive value for RFS (P<0.001, HR=2.362; 95%CI: 1.458-3.827) and OS (P=0.001; HR=2.388; 95%CI: 1.448-3.937) and XRCC1-399 had only a significant predictive value for RFS. And XRCC1-399 (A/A+A/G) genotype could significantly decrease the recurrence risk of patients (P<0.001, HR=0.569; 95%CI: 0.341-0.949). CONCLUSION: Gastric cancer patients with ERCC1-118 C/C genotype and XRCC1-399A/G or A/A genotype may benefit from an oxaliplatin-based adjuvant chemotherapy.

A multicenter study assessing the prevalence of germline genetic alterations in Chinese gastric-cancer patients.

BACKGROUND: Approximately 10% of patients with gastric cancer (GC) have a genetic predisposition toward the disease. However, there is scant knowledge regarding germline mutations in predisposing genes in the Chinese GC population. This study aimed to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer. METHODS: A total of 40 GC patients from 40 families were recruited from seven medical institutions in China. Next-generation sequencing was performed on 171 genes associated with cancer predisposition. For probands carrying pathogenic/likely pathogenic germline variants, Sanger sequencing was applied to validate the variants in the probands as well as their relatives. RESULTS: According to sequencing results, 25.0% (10/40) of the patients carried a combined total of 10 pathogenic or likely pathogenic germline variants involving nine different genes: CDH1 (n = 1), MLH1 (n = 1), MSH2 (n = 1), CHEK2 (n = 1), BLM (n = 1), EXT2 (n = 1), PALB2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). In addition, 129 variants of uncertain significance were identified in 27 patients. CONCLUSIONS: This study indicates that approximately one in every four Chinese GC patients with hereditary high risk factors may harbor pathogenic/likely pathogenic germline alterations in cancer-susceptibility genes. The results further indicate a unique genetic background for GC among Chinese patients.

[Anti-angiogenic effect of vinorelbine in combination with cetuximab in vitro and in vivo].

OBJECTIVE: This experiment aims to study the anti-angiogenic ability of vinorelbine combined with cetuximab in vitro and in vivo. METHODS: Human lung adenocarcinoma A549 cells were used as control group. Proliferation of human umbilical vein endothelial cells (HUVEC) was assessed by MTT assay. Furthermore, we used Transwell chambers, capillary tube formation and flow cytometry to observe the effects of vinorelbine combined with cetuximab on HUVEC migration, tube formation and cell apoptosis, respectively. In addition, the anti-angiogenic ability of the drugs was checked using chicken chorioallantoic membrane (CAM) model. RESULTS: The inhibitory rate of HUVEC growth was 25.8%, 39.2%, 54.0% for vinorelbine at the concentration of 0.1 ng/ml, 0.4 ng/ml, and 0.8 ng/ml, respectively; that of 0.25 microg/ml cetuximab was 19.7%, and that of 0.1 ng/ml vinorelbine + 0.25 microg/ml cetuximab, 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab and 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 29.5%, 46.4%, 64.6%, respectively. The inhibitory rates of the drugs at the above mentioned combinations of migration and tube formation of HUVEC were 51.9%, 68.2%, 95.0%, respectively. The inhibitory rate of 0.1 ng/ml + 0.25 microg/ml cetuximab and 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab on tube formation of HUVEC was 38.8% and 57.7%, respectively, showing a sub-additive effect, and that of combination of 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 78.9%, showing a synergistic effect. In addition, the apoptotic rate of HUVEC induced by 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 59.9%, showing a synergistic effect. The in vivo experiment also showed that the combination of the two drugs had a synergistic anti-angiogenic effect. CONCLUSION: Both low dose vinorelbine and cetuximab have an anti-angiogenic effect in vitro and in vivo, and the combination of the two drugs has sub-additive or synergistic inhibitory effect on angiogenesis.

beta-Tubulin III mRNA expression and docetaxel sensitivity in non-small cell lung cancer.

PURPOSE: Despite the success of docetaxel as an anti-tumour agent, the inter-individual variability in drug response still poses a major impediment to further use of this agent in the treatment of cancer. Current knowledge about predictive biomarkers of docetaxel sensitivity in malignant effusions is poor. The aim of this study was to investigate the association between beta-tubulin III mRNA expression and chemosensitivity to docetaxel in metastatic malignant effusions. METHODS: Real-time quantitative PCR was used for analysis of beta-tubulin III mRNA expression in 37 malignant effusions collected prospectively. Viable tumour cells obtained from malignant effusions were tested for sensitivity to docetaxel using ATP-TCA assay. RESULTS: beta-tubulin III expression was inversely correlated with sensitivity to docetaxel in pleural effusions of NSCLC patients (P =0.022). The lower level of beta-tubulin III mRNA expression in malignant effusions was associated with higher chemosensitivity to docetaxel in NSCLC patients in vitro. No correlation was found between beta-tubulin III mRNA expression and docetaxel sensitivity in malignant effusions of gastric cancer patient. CONCLUSION: Our results demonstrated that beta-tubulin III mRNA expression level in malignant effusions, in which all cancer cells were metastatic, was correlated with docetaxel sensitivity in NSCLC. This highlights the potential role of biomarkers in malignant effusions in further customized chemotherapy.

[Prognostic significance of ERCC1 mRNA expression in patients with non-small cell lung cancer receiving platinum-based chemotherapy].

OBJECTIVE: To investigate the correlation of the mRNA expression level of excision repair cross-complementing group 1 (ERCC1) gene with clinicopathological parameters and clinical outcome in patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy. METHODS: The mRNA expression of ERCC1 in formalin-fixed paraffin-embedded primary tumor specimens was measured by real-time quantitative reverse transcriptase polymerase chain reaction. The association between ERCC1 expression levels and clinicopathological parameters in NSCLC patients was analyzed. RESULTS: The median value of ERCC1 mRNA expression level compared with beta-actin in tumor specimens of 61 NSCLC patients was 0.48. There was no correlation between ERCC1 expression and clinicopathological parameters. Patients with low expression of ERCC1 mRNA (less than 0.35, 0.28, respectively) had a significantly longer median time to progression (TTP) (14.3 vs. 8.0 months, P = 0.028) and overall survival (OS) (28.4 vs. 12.9 months, P = 0.0064) than those with high expression. Multivariate analysis showed that a low ERCC1 mRNA expression was an independent factor for OS. CONCLUSION: Our findings suggest that intratumoral ERCC1 mRNA expression level, although is uncorrelated with clinicopathological parameters, is an independent predictive marker for survival of the patients with NSCLC receiving platinum-based chemotherapy, and may provide critical information for personalized chemotherapy.

Predictive value of thymidylate synthase expression in advanced colorectal cancer patients receiving fluoropyrimidine-based chemotherapy: evidence from 24 studies.

The published data about thymidylate synthase (TS) expression and its predictive value in advanced colorectal cancer (CRC) patients receiving fluoropyrimidine-based chemotherapy seemed inconclusive. To derive a more precise estimation of the relationship, a metaanalysis was performed. Studies have been identified by searching PubMed and Embase. Inclusion criteria were advanced CRC patients, received fluoropyrimidine-based chemotherapy and evaluation of TS expression and overall response rate (ORR). The relative ratio (RR) for ORR in patients with low-TS expression over those with high-TS expression with 95% confidence interval (CI) was calculated for each study as an estimation of the predictive effect of TS. A total of 24 studies including 1,112 patients were involved in this metaanalysis. The overall RR was 2.20 (95% CI, 1.82-2.66; p = 0.000). For studies evaluating TS expression in metastatic lesions, the pooled RR was 3.23 (95% CI, 2.27-4.59; p = 0.000); for studies testing TS expression in primary lesions, a pooled RR of 1.89 (95% CI, 1.45-2.48; p = 0.000) was estimated. Focusing the analysis on immunohistochemistry (IHC)-based or RTPCR-based assessments, the pooled RR was 1.83 (95% CI, 1.44-2.34; p = 0.000) and 2.96 (95% CI, 2.07-4.22; p = 0.000), respectively. The results indicated that low-TS expression tumors in advanced CRC patients were more sensitive to fluoropyrimidine-based chemotherapy. Subgroup analyses indicated that the predictive value of TS expression evaluated in metastases was more prominent than that of primary lesions, and that TS expression tested by RTPCR was also of greater predictive value than by IHC.

Proteomic analysis of anti-tumor effects by Rhizoma Paridis total saponin treatment in HepG2 cells.

Rhizoma Paridis total saponin (RPTS) had been identified as the major components responsible for the anti-tumor effects of the herb Rhizoma Paridis, which had been used in China for centuries to treat many diseases including tumor. To elucidate the anti-tumor mechanism of RPTS, a proteomic analysis was carried out with RPTS treatment in HepG2 cells. More than 50 proteins showed a significant change between control (0.01% DMSO) and RPTS (IC(50) approximately 10microg/ml) treated cells after 48h. Twelve proteins had been identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) using peptide fingerprinting from 15 protein spots (density difference >2 fold between the control and RPTS-treated group). Among them, six proteins were down-regulated (dUTPase, hnRNP K, GMP synthase, etc.) and six proteins were up-regulated (DNase gamma, Nucleoside diphosphate kinase A, Centrin-2, etc.) by RPTS treatment in HepG2 cells as determined by spot volume (p<0.05). Most of the identified proteins were associated with tumor initiation, promotion, and progression. These findings might offer valuable insights into the mechanism of anti-tumor effect affected by RPTS treatment in HepG2 cells.

[Differential gene expression of the inhibitor of apoptosis proteins in docetaxel-resistant gastric cancer cells].

OBJECTIVE: Resistance to chemotherapy may indicate an unfavorable outcome for patients with gastric cancer. The purpose of this study was to examine whether docetaxel-resistance could be due in part to the expression of the inhibitor of apoptosis proteins (IAP). METHODS: Docetaxel-resistant cells, BGC-823/R1, BGC-823/R2 and BGC-823/R3, were established from parent BGC-823 cells by stepwise increasing concentration of docetaxel. To characterize these cells, we examined the effects of docetaxel on cell growth and apoptosis by MTT assay and double staining with both annexin-V-FITC and PI, and analyzed the cross-resistance to various anticancer drugs. Expression of IAP compared with that in parental cells was evaluated by real-time quantitative PCR. RESULTS: The BGC-823 resistant cells, BGC-823/R1, R2 and R3 cells, were 10.2-, 24.5-, 56.3-fold more resistant to docetaxel than parental cells, respectively, and this resistance was paralleled with reduced induction of apoptosis. BGC-823/R3 cells showed cross-resistance to paclitaxel, whereas exhibited weak or no cross-resistance against 5-fluorouracil, cisplatin and oxaliplatin. The expressions of survivin and XIAP were gradually increased with the extent of docetaxel resistance (r = 0.909, P < 0.001 and r = 0.892, P < 0.001, respectively). CONCLUSION: IAP may make an important contribution to the resistance to the apoptotic effect of docetaxel in gastric cancer, and could be used as a potential therapeutic target.

Profiles of genomic alterations in primary esophageal follicular dendritic cell sarcoma: A case report.

RATIONALE: Follicular dendritic cell (FDC) sarcoma is a rare tumor with FDC differentiation that typically arises within lymph nodes but can also occur extranodally. To date, the primary esophageal FDC sarcoma has not been reported in the English literature. PATIENT CONCERNS: We described a 67-year-old female who foremostly presented with dysphagia, and the patient was readmitted due to a dry cough and pain of his right shoulder 2 years after initial treatment. DIAGNOSES: Primary esophageal FDC sarcoma with the right superior mediastinal lymph node metastasis. INTERVENTIONS: The esophageal tumor was removed by endoscopic submucosal dissection at the first hospitalization. At the second hospitalization 2 years after the initial visit, the tracheal stent loaded with (125) iodine radioactive seeds was placed. The profiles of genetic variations and immunotherapeutic biomarkers were also explored by next-generation sequencing protocol from the patient's blood, esophageal primary, and mediastinal metastatic tumor samples. OUTCOMES: The patient's symptom transitorily relieved, but she gave up further treatment and died 2 months after the tracheal stent was placed. As for the genomic alterations, we found 9 gene mutations in all the samples, including checkpoint kinase 2(CHEK2), FAT atypical cadherin 1 (FAT1), tumor protein 53 (TP53), DPYD, ERBB2 interacting protein (ERBB2IP), FBXW7, KMT2D, PPP2R1A, TSC2, whereas amplification of MYC was only in the metastatic example. The analysis of clonal evolution and phylogenetic tree showed the propagation and replay of polyclonal esophageal FDC sarcoma. At the same time, the detection of biomarkers for immunotherapy revealed microsatellite stable and mismatch repair-proficient (pMMR), which predicted a relatively poor anti-programmed death (PD-1)/programmed death ligand (PD-L1) immunotherapy outcome. On the contrary, the tumor mutational burdens were 10 mutations per 1 million bases in both the primary and metastatic tumor sample, which ranked the top 23.3% in solid tumors mutational burdens database of Geneseeq and might be a good predictor of the efficacy of anti-PD-1/PD-L1 immunotherapy. LESSONS: To the best of our knowledge, this case report announced the first case of extranodal primary esophageal FDC sarcoma in the world, and firstly revealed its unique genetic alterations profiles, which might contribute to further in-depth study of this rare disease.

Comparison of microsatellite status detection methods in colorectal carcinoma.

There are two commonly accepted methods for detecting microsatellite status. One is to detect amplified microsatellite loci by polymerase chain reaction (PCR) and the other is to detect mismatch repair gene (MMR) protein expression by immunohistochemistry (IHC). PCR detection is considered to be accurate in clinical operations while IHC is widely used due to ease of operation and lesser expense. In order to compare IHC with PCR in detecting microsatellite status in colorectal carcinoma, a total of 569 samples of colorectal carcinoma resection were collected in the Department of Pathology, Nanjing Drum Tower Hospital, between June 2014 and June 2017. In all samples, IHC and PCR was used to detect microsatellite status and the consistency of results between the two methods was compared. We found that 48 cases of microsatellite instability (MSI) were detected by PCR including 37 cases of microsatellite instability high (MSI-H), 11 cases of microsatellite instability low (MSI-L), and 521 cases of MSS. MSI accounted for 8.44% of all cases and MSI-H accounted for 6.50%. IHC results of the 569 patients showed that 69 cases were deficient mismatch repair (dMMR) and 500 cases were proficient mismatch repair (pMMR). dMMR accounted for 12.13% of all cases. Loss expression of PMS2 protein was the most common while MSH6 was rare. The coincidence rate of the two methods for detecting microsatellite states was 91.92%. IHC and the PCR method had high consistency in microsatellite status. Compared with PCR, the IHC method is more economical and more convenient for clinical operations. When the 4 repair proteins were without deficiency detected by IHC, it could be diagnosed as MSS/MSI-L and further PCR was not necessary. When any repair protein was found to be deficient, PCR detection was needed to determine whether MSI existed. Our conclusion will save a lot of time and costs in clinical work.

Dexamethasone-Induced Myeloid-Derived Suppressor Cells Prolong Allo Cardiac Graft Survival through iNOS- and Glucocorticoid Receptor-Dependent Mechanism.

How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs) are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated in vitro. However, none of current systems for in vitro differentiation of MDSCs have successfully achieved long-term immune tolerance. Herein, we combined dexamethasone (Dex), which is a classic immune regulatory drug in the clinic, with common MDSCs inducing cytokine granulocyte macrophage colony stimulating factor (GM-CSF) to generate MDSCs in vitro. Addition of Dex into GM-CSF system specifically increased the number of CD11b+ Gr-1int/low MDSCs with an enhanced immunosuppressive function in vitro. Adoptive transfer of these MDSCs significantly prolonged heart allograft survival and also favored the expansion of regulatory T cells in vivo. Mechanistic studies showed that inducible nitric oxide sythase (iNOS) signaling was required for MDSCs in the control of T-cell response and glucocorticoid receptor (GR) signaling played a critical role in the recruitment of transferred MDSCs into allograft through upregulating CXCR2 expression on MDSCs. Blockade of GR signaling with its specific inhibitor or genetic deletion of iNOS reversed the protective effect of Dex-induced MDSCs on allograft rejection. Together, our results indicated that co-application of Dex and GM-CSF may be a new and important strategy for the induction of potent MDSCs to achieve immune tolerance in organ transplantation.

Survivin: potential role in diagnosis, prognosis and targeted therapy of gastric cancer.

Survivin is a protein that is highly expressed in a vast number of malignancies, but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells, thus facilitating the growth of these cells. In the case of gastric cancer, survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells, it has been described as an "ideal target" for cancer therapy. Currently, several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis, prognosis and treatment of gastric tumors.

[Inhibitory effect of oxaliplatin in combination with hyperthermia on angiogenesis].

OBJECTIVE: To study the effect of oxaliplatin in combination with hyperthermia on angiogenesis in vitro and in vivo. METHODS: MTT method was used to observe the influence of oxaliplatin on the proliferation of human umbilical vein endothelial cells (HUVEC) or human colon cancer cells (LOVO). The influence of oxaliplatin on HUVEC migration was evaluated by Transwell. Chick embryo chorioallantoic membrane (CAM) model was used to check whether the neovascularization of CAM could be suppressed in vivo. RESULTS: The survival rate of HUVEC was 80.1% - 42.5% within a range of 0.5 - 16 microg/ml and was negatively correlated with the concentration (correlation coefficient was - 0. 943, P = 0.005). The survival rate of LOVO cells within those doses was more than that of HUVEC. There was a synergistic antiangiogenic effect when a combination of oxaliplatin (0.5 microg/ml, 1 microg/ml and 16 microg/ml) with hyperthermia was used while additional effect was shown by the combinatioin of oxaliplatin (2 microg/ml, 4 microg/ml and 8 microg/ml) and hyperthermia in vitro. Oxaliplatin inhibited migration of HUVEC in vitro at low doses (0.25 - 2 microg/ml), and also suppressed angiogenesis of CAM in vivo at doses of 1 -4 microg/ml. CONCLUSION: The results of this experiment showed that low dose of oxaliplatin has anti-angiogenic effect in vitro, while in combination with hyperthermia has additional effect both in vivo and in vitro.