Elevated Preoperative NMPR Predicts an Unfavorable Chance of Survival in Resectable Esophageal Squamous Cell Carcinoma.

Background and objectives: Combined peripheral neutrophil−platelet indexes reflecting the systemic inflammatory status have been reported to predict the clinical outcome in patients with various types of cancer. However, the prognostic value of combined neutrophil−platelet indexes in operable esophageal squamous cell carcinoma (ESCC) remains unclear. The study introduced a novel combined neutrophil−meanplateletvolume−platelet ratio (NMPR) index and investigated its clinical and prognostic value in patients with operable ESCC receiving curative surgery. Materials and Methods: A retrospective analysis of the clinicopathologic data of 277 consecutive ESCC patients who received curative resection at Zhejiang Cancer Hospital in China between January 2007 and December 2010 was conducted (the training cohort). In addition, the clinicopathologic data of 101 resectable ESCC patients at Renmin Hospital of Hubei University of Medicine between December 2018 and June 2021 were collected (the external validation cohort). The optimal cutoff value of NMPR concerning overall survival (OS) in the training cohort was determined by X-tile software. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of NMPR along with other variables in the training cohort, which was further validated with the same cutoff value in the external validation cohort. Significant predictors of OS were used to construct the nomogram, of which the discrimination and calibration was evaluated by concordance index (C-index) and calibration plots. Results: With a cutoff value of 16.62, the results from both the training and external validation cohorts supported the association of high NMPR (>16.62) with increased tumor length and advanced T stage but not with other variables. In the training cohort, a significant association between shorter OS and high NMPR (p = 0.04) as well as high CRP (p < 0.001), poor tumor differentiation (p = 0.008), advanced T stage (p = 0.006), advanced N stage (p < 0.001) and high CEA (p = 0.007) was revealed. Additionally, the high NMPR was verified to independently predict unfavorable OS (p = 0.049) in the external validation cohort. The C-index of the OS nomogram cooperating significant predictors in the training cohort was 0.71 and the calibration plots of the OS nomogram fitted well. Conclusions: The present study demonstrates that high NMPR is an independent predictor of unfavorable OS in resectable ESCC patients without neoadjuvant therapy.

Dexmedetomidine inhibits the growth and metastasis of esophageal cancer cells by down-regulation of lncRNA MALAT1.

This study aims to evaluate the effect of dexmedetomidine (DEX)-on esophageal cancer (EC) via regulating long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). The effect of DEX on MALAT1 expression and EC cell viability was detected. EC cells were divided into Blank, DEX, scrambled/MALAT1 siRNA, and DEX + control/MALAT1 groups, followed by a series of experiments including quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blotting, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), Annexin V-FITC/PI staining, wound healing, and Transwell assays. Additionally, mice were subjected to the subcutaneous injection of Eca109 cells transfected by control/MALAT1 activation lentiviral vector to construct EC models with the DEX treatment, and then the tumor volume and the expression of Ki-67 and active caspase-3 were determined. DEX reduced the expression of MALAT1 in EC cells in a dose-dependent manner. DEX inhibited the viability of EC cells, but increased the cell apoptosis, which, however, was reversed by MALAT1 overexpression. Moreover, MALAT1 overexpression abolished the inhibitory effect of DEX on the epithelial-mesenchymal transition (EMT) of EC cells, with enhanced migration and invasion. Furthermore, DEX succeeded in decreasing the tumor volume with the down-regulation of MALAT1. In comparison with the DEX group, mice in the DEX + MALAT1 group had larger tumors, with the up-regulation of Ki-67 and the down-regulation of active caspase-3. DEX can reduce the expression of MALAT1 in EC cells, thereby inhibiting the proliferation, invasion and migration, as well as EMT, and promoting the apoptosis of EC cells.

High C-Reactive Protein to Albumin Ratio Predicts Inferior Clinical Outcomes in Extranodal Natural Killer T-Cell Lymphoma.

OBJECTIVE: The prognostic value of C-reactive protein to albumin ratio (CAR) has been identified in several cancers but not in extranodal natural killer T-cell lymphoma (ENKTL) as yet. We aimed to evaluate the prognostic value of CAR in ENKTL. METHODS: A retrospective study with 246 patients with ENKTL was performed to determine the prognostic value of pretreatment CAR and examine the prognostic performance of CAR incorporating with International Prognostic Index (IPI) or natural killer/T-cell lymphoma prognostic index (NKPI) by nomogram. RESULTS: The Cox regression analyses showed that high CAR (>0.3) independently predicted unfavorable progression-free survival (PFS, P = .011) and overall survival (OS, P = .012). In the stratification analysis, the CAR was able to separate patients into different prognoses regarding both OS and PFS in Ann Arbor stage I+II as well as III+IV, IPI score 0 to 1, and NKPI score 1 to 2 subgroups (all P < .05). Additionally, the predictive accuracy of the IPI-based nomogram incorporating CAR, albumin to globulin ratio (AGR), and IPI for OS and PFS appeared to be lower than the NKPI-based nomogram incorporating CAR, age, AGR, extranodal site, and NKPI. CONCLUSION: Pretreatment CAR is a simple and easily accessible parameter for independently predicting OS and PFS in patients with ENKTL.

GPX2 overexpression indicates poor prognosis in patients with hepatocellular carcinoma.

Glutathione peroxidase 2 has important role of tumor progression in lots of carcinomas, yet little is known about the prognosis of glutathione peroxidase 2 in hepatocellular carcinoma. Glutathione peroxidase 2 expression was assessed by immunohistochemistry in hepatocellular carcinoma tissues. The association between glutathione peroxidase 2 expression with clinicopathological/prognostic value was examined. Glutathione peroxidase 2 overexpression was correlated with alpha-fetoprotein level, larger tumor, BCLC stage, and tumor recurrence. Kaplan-Meier analysis showed that glutathione peroxidase 2 was an independent predictor for overall survival and time to recurrence. glutathione peroxidase 2 overexpression was correlated with poor prognosis in patient subgroups stratified by tumor size, differentiation, tumor-node-metastasis, and BCLC stage. Moreover, stratified analysis showed that tumor-node-metastasis stage-I patients with high glutathione peroxidase 2 expression had poor prognosis than those with low glutathione peroxidase 2 expression. Additionally, combination of glutathione peroxidase 2 and serum alpha-fetoprotein was correlated with prognosis in hepatocellular carcinoma. In conclusion, glutathione peroxidase 2 overexpression contributes to poor prognosis of hepatocellular carcinoma patients and helps to identify the high-risk hepatocellular carcinoma patients.

Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

BACKGROUND: The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. METHODS: A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. RESULTS: Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. CONCLUSION: The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma.

Cyclooxygenase-2 polymorphisms and bladder cancer risk: a meta-analysis based on case-control studies.

The current meta-analysis incorporating 15 case-control studies involving 4,138 cases and 4,269 controls was performed on the basis of a systematical search in electronic databases for a more precise estimation on the associations of three common polymorphisms -765 G>C (rs20417), -1195G>A (rs689466) and +8473 C>T (rs5275) in Cyclooxygenase-2 (Cox-2) gene with the susceptibility to bladder cancer. The results showed that there was a significant association between rs5275 polymorphism and bladder cancer risk (C vs. T; OR=0.84; CC vs. TT: OR=0.76), especially among Chinese (CC vs. TC+TT: OR=0.48) and American (C vs. T; OR=0.83; TC vs. TT: OR=0.73; CC+TC vs. TT: OR=0.73). and the rs20417 polymorphism was significantly associated with an increased risk of bladder cancer among Chinese (C vs. G: OR=1.46; GC vs. GG: OR=1.49; CC+GC vs. GG: OR=1.51) and Indian (GC vs. GG: OR=1.63; CC+GC vs. GG: OR=1.46), but a reduced risk among American (C vs. G: OR=0.81; GC vs. GG: OR=0.76; CC+GC vs. GG: OR=0.76). Additionally, we found that the rs689466 polymorphism was associated with a decreased risk of bladder cancer in Indian (GA vs. GG: OR=0.68; AA vs. GG: OR=0.39).The present meta-analysis suggests that Cox-2 rs5275 polymorphism may contribute to the risk of bladder cancer, particularly among Chinese and American. The rs20417 polymorphism may play a protective role in the development of bladder cancer in Indian and Chinese but act as a risk factor among American, while the rs689466 polymorphism was more likely to be associated with a decreased risk of bladder cancer in Indian.

[Clinical analysis of 6 cases of primary small cell carcinoma of the larynx].

OBJECTIVE: To study the clinical characteristics, pathological features, diagnosis, therapy and prognosis of primary small cell carcinoma of the larynx (PSCCL). METHODS: Six cases of PSCCL collected from 1990 to 2009 was retrospectively analyzed. The diagnosis was confirmed by pathological examination. Among six patients, one case belonged to stage III, and the others were in stage IVA. One case abandoned treatment; one case received chemotherapy; one case underwent supraglottic hemilaryngectomy and adjuvant chemoradiotherapy; one case underwent induction chemotherapy, radiotherapy and consolidation chemotherapy. Two cases received induction chemotherapy, concurrent chemoradiation and consolidation chemotherapy. The drug regimens included bleomycin, fluorouracil, cisplatin, etoposide and taxel for 3-6 cycles. The radiotherapy technique included conventional radiotherapy, CT-Sim and three dimensional conformal radiation therapy with (60)Co or 4 MV X-ray for 60 - 66 Gy during 6 - 7 weeks. RESULTS: The time of follow-up was 3 - 24 months and the median was 13 months. Two patients applied with concurrent chemoradiation were alive without tumor. The patient abandoning therapy died of respiratory failure, and the others died of lung or liver metastasis after 8 - 12 months. CONCLUSIONS: PSCCL is a disseminated disease, so the pretreatment evaluation is necessary. Concurrent chemoradiation is an ideal treatment model for this disease.

Ethyl (2,5-dioxo-1-phenyl-2,3-dihydro-1H,5H-1-benzofuro[3,2-d]imidazo[1,2-a]pyrimidin-3-yl)acetate.

In the title compound, C(22)H(17)N(3)O(5), synthesized via the aza-Wittig reaction of ethyl 3-(phenyl-imino-methyl-ene-amino)-benzofuran-2-carboxyl-ate, benzene isocyanate and diethyl 2-amino-succinate, the imidazo[1,2-a]benzo[4,5]furo[2,3-d]pyrim-idine ring system is essentially planar (r.m.s. deviation for all 16 non-H atoms = 0.020 Å). The phenyl ring is twisted with respect to this ring system, making a dihedral angle of 54.23 (4)°. The crystal packing is stabilized by weak inter-molecular C-H⋯O inter-actions.

Ethyl 1-benzyl-5-{[(isopropyl-amino)(3-nitro-phen-oxy)methyl-idene]amino}-1H-1,2,3-triazole-4-carboxyl-ate.

In the title compound, C(22)H(24)N(6)O(5), the triazole ring is essentially planar with a maximum deviation of 0.005 (2) Šand forms dihedral angles of 79.78 (11) and 86.22 (11)° with the phenyl and benzene rings, respectively. In the crystal, mol-ecules are linked by inter-molecular N-H⋯N, C-H⋯O and C-H⋯π inter-actions into a three-dimensional network.

3-Benzyl-6-isopropyl-5-phen-oxy-3H-1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-one.

In the title compound, C(20)H(19)N(5)O(2), all atoms of the 1,2,3-triazolo[4,5-d]pyrimidine ring system are essentially coplanar [maximum deviation = 0.015 (2) Å], indicating the existence of a conjugate system in which each carbon and nitrogen atom is sp(2) hybridized and ten π electrons (three from carbon atoms and seven from nitrogen atoms) constitute an aromatic heterocycle. The ring system forms dihedral angles of 68.37 (10) and 71.57 (9)° with the phenyl rings. The crystal packing is stabilized by van der Waals inter-actions and intermolecular C-H⋯π interactions.

[Reversal effect of PI-3K/Akt pathway inhibitor LY294002 on multidrug resistance of ovarian cancer cell line A2780/Taxol].

BACKGROUND & OBJECTIVE: Previous studies had showed that phosphatidylinositol 3 kinase (PI-3K) can suppress cell apoptosis. The inhibitor of PI-3K has been used to investigate the mechanisms of PI-3K-induced oncogenesis. This study was to investigate the reversal effect of LY294002, a PI-3K/Akt inhibitor, on paclitaxel-resistance of ovarian carcinoma cell line A2780/Taxol. METHODS: A2780/Taxol cells were treated with LY294002. Cell apoptosis was analyzed by flow cytometry (FCM). The 50% inhibition concentration (IC50) of paclitaxel for A2780/Taxol cells was determined by MTT assay. The expression of multidrug resistance 1 (MDR1) mRNA was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The expression of phosphated Akt and P-glycoprotein (P-gp) were detected by Western blot. RESULTS: When treated for 24 h, the apoptosis rate of A2780/Taxol cells was significantly higher in 10 and 50 micromol/L LY294002 groups than in control group [(8.84+/-1.65)% and (20.78+/-2.47)% vs. (1.25+/-0.78)%, P<0.05], the IC50 of paclitaxel for A2780/Taxol cells was decreased significantly (P<0.01) with the highest reverse efficiency of (78.08+/-0.37)%. Moreover, the expression of MDR1 gene, and the phosphorylation of Akt and P-gp in A2780/Taxol cells were decreased. CONCLUSIONS: The activation of PI-3K/Akt pathway plays an important role in paclitaxel-resistance of ovarian carcinoma cells. PI-3K/Akt inhibitor, LY294002 has a reversal effect on the paclitaxel-resistance of A2780/Taxol cells.