A COX2-targeting cancer-specific fluorescent probe for hydrogen sulfide detection in living cells, Caenorhabditis elegans, and zebrafish.

A novel cyclooxygenase-2 (COX-2) targeted H2S-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This H2S-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, Caenorhabditis elegans (C. elegans), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous H2S in living cells, demonstrating high sensitivity and specificity and strong anti-interference. COX2-H2S had the ability to not only discern cancer cells from normal cells but also specifically recognize 9L/lacZ cells from other glioblastoma cells (U87-MG and LN229). It could also be successfully applied for the fluorescent live imaging of H2S in both C. elegans and zebrafish.

Application value of nomogram and prognostic factors of gastric cancer patients who underwent D2 radical lymphadenectomy.

BACKGROUND: The aim of this study was to explore the prognostic factors and establish a nomogram to predict the long-term survival of gastric cancer patients. METHODS: The clinicopathological data of 421 gastric cancer patients, who were treated with radical D2 lymphadenectomy by the same surgical team between January 2009 and March 2017, were collected. The analysis of long-term survival was performed using Cox regression analysis. Based on the multivariate analysis results, a prognostic nomogram was formulated to predict the 5-year survival rate probability. RESULTS: In the present study, the total overall 3-year and 5-year survival rates were 58.7 and 45.8%, respectively. The results of the univariate Cox regression analysis revealed that tumor staging, tumor location, Borrmann type, the number of lymph nodes dissected, the number of lymph node metastases, positive lymph nodes ratio, lymphocyte count, serum albumin, CEA, CA153, CA199, BMI, tumor size, nerve invasion, and vascular invasion were prognostic factors for gastric cancer (all, P < 0.05). However, merely tumor staging, tumor location, positive lymph node ratio, CA199, BMI, tumor size, nerve invasion, and vascular invasion were independent risk factors, based on the results of the multivariate Cox regression analysis (all, P < 0.05). The nomogram based on eight independent prognostic factors revealed a well-degree of differentiation with a concordance index of 0.76 (95% CI: 0.72-0.79, P < 0.001), which was better than the AJCC-7 staging system (concordance index = 0.68). CONCLUSION: The present study established a nomogram based on eight independent prognostic factors to predict long-term survival in gastric cancer patients. The nomogram would be beneficial for more accurately predicting the prognosis of gastric cancer, and provide important basis for making individualized treatment plans following surgery.

Safety and efficacy of nimotuzumab in combination with radiotherapy for patients with squamous cell carcinoma of the esophagus.

BACKGROUND: We investigated nimotuzumab (h-R3), a humanized monoclonal antibody against epidermal growth factor receptor, when combined with irradiation or chemoradiation for squamous cell carcinoma (SCC) of the esophagus. The aim of this study was to evaluate its safety and efficacy. METHODS: We retrospectively analyzed 66 patients with esophageal SCC treated with a combination of h-R3 and radiation or chemoradiation between December 2008 and September 2011 at Fudan University Shanghai Cancer Center. Fifty-two of the 66 patients received h-R3 combined with chemoradiation and 14 received h-R3 plus radiation. The median total irradiation dose was 61 Gy given by conventional fractionation. The h-R3 weekly dosage was 100 mg (6/66), 200 mg (54/66), or 400 mg (6/66) given concurrently during the irradiation period. RESULTS: Patients tolerated the treatment well. Grade 3-4 adverse events and toxicities occurred in 50 % of the patients. h-R3-related toxicities manifested as Grade 1 skin rash in 1 case and Grade 2 infusion-related reaction in 2 cases. The median overall survival (OS) and progression-free survival (PFS) were 26.0 months and 16.7 months, respectively. OS, PFS and locoregional control (LC) at 2 years were 54, 37 and 80 %, respectively. CONCLUSIONS: h-R3 in combination with irradiation or chemoradiation was safe and tolerable, and yielded encouraging OS, PFS and LC.

Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

Current evidence on the relationship between three polymorphisms in the XRCC7 gene and cancer risk.

Inconsistency of the association of polymorphisms of XRCC7 with cancer is noted. Three commonly studied XRCC7 polymorphisms including rs7003908 (T>G), rs7830743 (A>G), and rs10109984 (T>C) were selected to explore their association with risk of development of cancer by meta-analysis of published case-control studies. The results showed that no significant associations with cancer risk were found in any model in terms of rs7003908, rs7830743 and rs10109984 when all studies were pooled into the meta-analysis. But when stratified by cancer type, statistically significantly elevated cancer risk was only found in prostate cancer for rs7003908 (GG vs. TT: OR = 1.845, 95 % CI = 1.178-2.888; dominant model: OR = 1.423, 95 % CI = 1.050-1.929; recessive model: OR = 1.677, 95 % CI = 1.133-2.482). In the subgroup analysis by ethnicity or study design, no significantly increased risks were found for all three polymorphisms. This meta-analysis suggests that XRCC7 rs7003908 polymorphism may contribute to cancer susceptibility for prostate cancer, which is recommended to be included in future large-sample studies and functional assays.

Clinicopathological features, treatment modalities, and prognosis of esophageal neuroendocrine carcinoma: A single-center retrospective study.

OBJECTIVES: Esophageal neuroendocrine carcinoma (ENEC) is a rare cancer that is highly malignant and related to a poor prognosis. In this retrospective study we aimed to elucidate the clinical characteristics, diagnosis and management of patients with ENEC and to evaluate the potential prognostic factors. METHODS: Altogether 82 patients diagnosed with ENEC between January 2009 and December 2020 at the Fudan University Shanghai Cancer Center were retrospectively enrolled. Patients' survival was analyzed using the Kaplan-Meier and log-rank methods. Univariate and multivariate analyses and a Cox regression model were used to identify the prognostic factors. RESULTS: The median overall survival (mOS) was 13 months in all patients. Multivariate analysis revealed that advanced tumor stage (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.07-6.66, P = 0.0353), liver (HR 3.36, 95% CI 1.53-7.41, P = 0.0026) and lung metastasis (HR 3.37, 95% CI 1.20-9.51, P = 0.0214) were associated with a poor prognosis. While positive chromogranin A (CgA) expression was related to a favorable outcome (HR 0.21, 95% CI 0.09-0.49, P < 0.001). Also, patients had adjustment of chemotherapy (dose reduction or less than three cycles) were prone to a worse prognosis compared with those did not (HR 4.36, 95% CI 2.10-9.08, P < 0.001). CONCLUSION: In patients with ENEC, advanced cancer stage, adjustment of chemotherapy, liver and lung metastasis were associated with a poor survival, while CgA expression was related to a favorable prognosis.

A phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus.

Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor monoclonal antibody. We conducted a phase I study to assess the safety, tolerance, maximal tolerance dose (MTD) and efficacy of h-R3 in combination with concurrent chemoradiation in patient with locally advanced esophageal carcinoma. Patients with locally advanced squamous cell carcinoma of esophagus were eligible. A total dose of 61.2 Gy was delivered by conventional fractionation. Chemotherapy was concurrently administered with irradiation every 4 weeks with PF regimen (cis-platinum of 25 mg/m(2)/d, d1-3; 5-Fu of 1,800 mg/m(2), intravenously infusion in 72 h) for 4 cycles. h-R3 was administrated weekly during irradiation for 6 weeks. h-R3 dose escalation started with 100 mg/week, and followed by 200 mg/week and 400 mg/week. Three patients were enrolled in of each dose cohort. 11 patients were enrolled in the trial with 3, 4 and 4 in 100 mg/week, 200 mg/week and 400 mg/week cohort, respectively. 2 patients in 200 mg/week and 400 mg/week cohort were withdrawn due to patients' own decisions. No dose limiting toxicity was observed. Grade 3-4 of esophagitis, Grade 3 of leucocytopenia and neutrocytopenia occurred in 18% (2/11), 18% (2/11) and 9% (1/11) of patients, respectively. For nimotuzumab-related toxicity only one patient experienced Grade 1 skin rash, and no Grade ≥ 3 of toxicity was noticed. In 9 patients, who completed planned treatments, 6-month and 1-year overall survival were 78% and 67%, respectively, and 1 year local progression-free survival, 100%. h-R3 of 400 mg/week administered concurrently with chemoradiation was well-tolerant. MTD has not been reached yet.

miR-196a2 C allele is a low-penetrant risk factor for cancer development.

Published data on the association between miR-196a2 T/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 21 studies including 10,441 cases and 12,353 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with miR-196a2 C allele when all studies were pooled into the meta-analysis (TC vs. TT: OR=1.23, 95% CI=1.11-1.36; CC vs. TT: OR=1.30, 95% CI=1.14-1.48; dominant model: OR=1.25, 95% CI=1.13-1.38). In the subgroup analysis by ethnicity, significantly increased risks were found in Asains (TC vs. TT: OR=1.24, 95% CI=1.10-1.40; CC vs. TT: OR=1.31, 95% CI=1.13-1.52; dominant model: OR=1.26, 95% CI=1.12-1.41) but with bordline statistical significance in Caucasians (TC vs. TT: OR=1.15, 95% CI=1.00-1.31). In the subgroup analysis by cancer type, statistically significantly increased risks were found for breast cancer (TC vs. TT: OR=1.15, 95% CI=1.01-1.31; CC vs. TT: OR=1.30, 95% CI=1.01-1.68; dominant model: OR=1.22, 95% CI=1.00-1.50; and recessive model: OR=1.11, 95% CI=1.01-1.23) and lung cancer (CC vs. TT: OR=1.30, 95% CI=1.10-1.54; and recessive model: OR=1.18, 95% CI=1.02-1.36). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TC vs. TT: OR=1.30, 95% CI=1.13-1.49; CC vs. TT: OR=1.37, 95% CI=1.14-1.66; dominant model: OR=1.32, 95% CI=1.15-1.53) and population-based studies (CC vs. TT: OR=1.19, 95% CI=1.06-1.35; dominant model: OR=1.13, 95% CI=1.01-1.25). Despite some limitations, this meta-analysis suggests that the miR-196a2 C allele is a low-penetrant risk factor for cancer development.

Lack of association between methylenetetrahydrofolate reductase gene A1298C polymorphism and breast cancer susceptibility.

Published data on the association between methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR A1298C polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (AC vs. AA, CC vs. AA), dominant model (CC+AC vs. AA), and recessive model (CC vs. AC+AA), respectively. A total of 26 studies including 12,244 cases and 15,873 controls were involved in this meta-analysis. Overall, no significant associations were found between MTHFR A1298C polymorphism and breast cancer risk when all studies pooled into the meta-analysis (AC vs. AA: OR=0.99, 95% CI 0.94-1.05; CC vs. AA: OR 0.99, 95% CI 0.90-1.09; dominant model: OR=0.99, 95% CI 0.95-1.04; and recessive model: OR=0.98, 95% CI 0.90-1.08). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MTHFR A1298C polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.

Chlorido[1-(diphenyl-phosphan-yl)cobaltocenium]gold(I) hexa-fluoridophosphate.

In the cobaltocenium group of the title compound, [AuCo(C(5)H(5))(C(17)H(14)P)Cl]PF(6), the substituted cyclo-penta-dienyl (Cps) and the unsubstituted cyclo-penta-dienyl (Cp) ring planes are almost parallel, making a dihedral angle of 3.1 (3)°. The C atoms in Cp and Cps are in an eclipsed conformation. The Au(I) atom is coordinated by a P atom from the diphenyl-phosphanyl group and a Cl atom in an almost linear arrangement [P-Au-Cl = 178.15-(7)°]. Two hexa-fluorido-phosphate anions are each located on a twofold rotation axis. In the crystal, the complex cations and hexa-fluorido-phosphate anions are linked via inter-molecular C-H⋯F hydrogen bonds.

Visual outcomes of surgical and conservative treatment in children with small posterior polar cataracts and posterior lenticonus.

AIM: To compare the visual outcomes of children with small (≤3 mm) posterior polar cataracts (PPC) and posterior lenticonus who had cataract extraction surgery with the visual outcomes of those who were managed conservatively. METHODS: Children who initially had small PPC and posterior lenticonus who were followed up over 1-year period were retrospective reviewed in the study. Patients receiving surgery were compared with those receiving conservative therapy. The axial length, keratometry, refraction, best-corrected visual acuity (BCVA), and strabismus measurements were recorded. Lens morphology, i.e., the location, size, and depth of the cataract lesion, was measured with a Scheimpflug imaging system. To help control for baseline differences in the groups, patients were matched with controls by propensity score methodology. RESULTS: The study evaluated 60 patients (30 in the surgery group and 30 in the conservative therapy group) after matching by propensity score. Patients who underwent cataract surgery showed greater BCVA improvements (0.36±0.24 logMAR) than patients who were treated without surgery (0.22±0.26 logMAR; P=0.036). Surgery was effective in patients with a rear projection length (RPL) less than 1.0 mm and a pretreatment BCVA worse than 0.52 logMAR. CONCLUSION: Children with small PPC and posterior lenticonus who undergo cataract surgery experience greater BCVA improvements than those managed conservatively. Certain patients presenting with a RPL less than 1.0 mm and a pretreatment BCVA of 0.52 logMAR or worse may benefit from surgery.

Microribonucleic Acid-15a-5p Alters Adriamycin Resistance in Breast Cancer Cells by Targeting Cell Division Cycle-Associated Protein 4.

OBJECTIVE: Although chemotherapy is one of the first line clinical treatment of tumors, the efficacy of chemotherapy has been severely restricted by the frequent occurrence of drug resistance phenomenon. Multiple studies found that miRNAs can regulate the chemosensitivity of tumor cells. Here, this study aimed to assess the potential role of the miR-15a-5p/cell division cycle-related protein 4 (CDCA4) axis in breast cancer (BC) resistance to Adriamycin. METHODS: In the present study, the relative expression of miRNA-15a-5p in MCF-7/ADR, MCF-7 and Hs578Bst was measured by qRT-PCR. MCF-7/ADR cells underwent transfection with an miR-15a-5p mimic and inhibitor, respectively. Transwell assays, flow cytometry and CCK8 were performed to examine the potential effects of the abnormal expression of miR-15a-5p. The association of aberrant miR-15a-5p expression with Adriamycin resistance in BC was determined in cultured MCF-7/ADR cells. Bioinformatics was employed to predict the genes targeted by miR-15a-5p. Moreover, the correlation between miR-15a-5p and its target gene, CDCA4, was evaluated based on qRT-PCR data. RESULTS: The expression of miR-15a-5p was significantly downregulated in MCF/ADR cells compared with MCF-7 and Hs578Bst cell lines. In the presence of Adriamycin, miR-15a-5p overexpression significantly increased cell chemosensitivity, as well as MCF-7/ADR cell proliferation, invasion, and migration, while promoting apoptosis and inducing cell-cycle arrest in the synthesis phase. CDCA4 RNA interference enhanced these effects as shown in our previous study. Bioinformatics identified CDCA4 as an miR-15a-5p target gene. qRT-PCR further demonstrated that CDCA4 and miR-15a-5p expression levels were inversely correlated. CONCLUSION: Adriamycin resistance in BC cells was, at least in part, altered by mRNA-15a-5p via regulation of its target gene, CDCA4, by controlling the cell cycle, which may provide some novel ideas for BC chemotherapy in the future.

MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls.

Published data on the association between MTHFR C677T polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR C677T polymorphism and breast cancer risk. The pooled ORs were performed with co-dominant model (CT vs. CC, TT vs. CC), dominant model (CT + TT vs. CC), and recessive model (TT vs. CC + CT), respectively. A total of 37 studies including 15,260 cases and 20,411 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with TT variant genotype in homozygote comparison and dominant genetic model when all studies were pooled into the meta-analysis (TT vs. CC: OR = 1.11, 95% CI = 1.01-1.23; dominant model: OR = 1.04, 95% CI = 1.00-1.09). In the subgroup analysis by ethnicity, significantly increased risks were found for TT allele carriers among Asians (TT vs. CC: OR = 1.18, 95% CI = 1.04-1.35; recessive model: OR = 1.15, 95% CI = 1.03-1.29). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TT vs. CC: OR = 1.18, 95% CI = 1.02-1.38; recessive model: OR = 1.17, 95% CI = 1.05-1.29). In the subgroup analysis by menopausal status, statistically significantly increased risk was found among postmenopausal women (CT vs. CC: OR = 1.12, 95% CI = 1.02-1.23; dominant model: OR = 1.11, 95% CI = 1.01-1.22). In conclusion, this meta-analysis suggests that the MTHFR T allele is a low-penetrant risk factor for developing breast cancer.

Effect of clinicopathologic features on survival of patients with thymic carcinomas and thymic neuroendocrine tumors: A population-based analysis.

BACKGROUND: Thymic carcinomas (TCs) and thymic neuroendocrine tumors (TNETs) are aggressive cancers with poor survival outcome and limited investigation. This study is to investigate clinicopathologic features on TC and TNET patients' prognosis of a large cohort. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database were used to identify a total of 362 TC and TNET patients with documented clinicopathologic features we investigated. The characteristics and overall survival of the TC and TNET patients were studied. RESULTS: Two hundred and forty TC and 122 TNET patients were identified. For the entire cohort of TC and TNET, histologic type (P < 0.001), tumor size (P = 0.015), Masaoka-Koga stage (P = 0.008), regional node positive (P = 0.004), surgery of primary site (P < 0.001), lymph node surgery (P = 0.013), and chemotherapy (P = 0.001) were considered as significant clinicopathologic features that could affect prognosis of TC and TNET patients in univariate analysis. More importantly, histologic type (P < 0.001), regional nodes positive (P = 0.03) and surgery of primary site (P < 0.001) were able to independently predict overall survival of those patients. In addition, for the cohort of TC, we found that regional nodes positive (P = 0.034) and surgery of primary site (P = 0.001) could be independent predictors of TC patients' survival. CONCLUSION: Regional nodes detection is essential for TC and TNET patients. Surgery of primary site is the preferred primary treatment for those patients.

Relationship between celiac artery variation and number of lymph nodes dissection in gastric cancer surgery.

BACKGROUND: Radical D2 lymphadenectomy for advanced gastric cancer as a standard procedure has gained global consensus. Mounting studies have shown that the number of lymph nodes dissection directly affects the prognosis and recurrence of gastric cancer. Our previous study showed that there was no obvious lymph node around the abnormal hepatic artery derived from the superior mesenteric artery. AIM: To investigate the relationship between celiac artery variation and the number of lymph nodes dissection in gastric cancer surgery. METHODS: The clinicopathological data of 421 patients treated with radical D2 lymphadenectomy were analyzed retrospectively. The difference of the number of lymph nodes dissection between the celiac artery variation group and the normal vessels group and the relationship with prognosis were analyzed. RESULTS: Celiac artery variation was found in 110 patients, with a variation rate of 26.13%. Celiac artery variation, tumor staging, and Borrmann typing were factors that affected lymph node clearance in gastric cancer, and the number of lymph nodes dissection in patients with celiac artery variation was significantly less than that of non-variant groups (P < 0.05). Univariate analysis showed that there was no significant difference in survival time between the two groups (P > 0.05). Univariate and multiple Cox regression analysis showed that celiac artery variation was not a prognostic factor for gastric cancer (P > 0.05). Tumor staging, intraoperative bleeding, and positive lymph node ratio were prognostic factors for gastric cancer patients (all P < 0.05). CONCLUSION: The number of lymph nodes dissection in patients with celiac artery variation was reduced, but there was no obvious effect on prognosis. Therefore, lymph nodes around the abnormal hepatic artery may not need to be dissected in radical D2 lymphadenectomy.

1-Diphenyl-phosphino-1'-(diphenyl-phosphinoyl)cobaltocenium hexa-fluorido-phosphate.

The title compound, [Co(C(17)H(14)OP)(C(17)H(14)P)]PF(6), was obtained unintentionally as the product of an attempted synthesis of [1,1'-bis-(oxodiphenyl-phospho-ranyl)cobaltocenium] hexa-fluorido-phosphate. The O atom of the oxo group is disordered over two positions with site occupancies of 0.65:0.35. The crystal structure contains weak inter-molecular C-H⋯F hydrogen bonds, connecting the components of the structure into chains parallel to [010].

Therapeutic cancer vaccines: From initial findings to prospects.

With the approval of the first therapeutic cancer vaccine by US Food and Drug Administration, numerous therapeutic cancer vaccines have been under clinical trials with an inspiring antitumor immune response in cancer patients. Though there is no therapeutic cancer vaccine showing clinical efficacy in phase III trials, recent advances in personalized cancer vaccine based on neoantigens have emerged as an efficient way to induce tumor regression. In this review, we discuss the selection methods of tumor specific antigen and mainly focus on the development of therapeutic cancer vaccine strategies. Besides, we highlight the newly developed personalized cancer vaccine as a novel therapeutic approach for cancer patients. Finally, we outline the recent development of therapeutic cancer vaccine in clinical trials.

Signal transduction involved in protective effects of 15(R/S)-methyl- lipoxin A(4) on mesangioproliferative nephritis in rats.

Studies have shown that lipoxin A(4) (LXA(4)) inhibited proliferation of mesangial cells in vitro induced by platelet-derived growth factor, epidermal growth factor, leukotriene D(4) or tumor necrosis factor-alpha. In this study, we investigated the protective effects of 15(R/S)-methyl-LXA(4) on mesangioproliferative nephritis in rats and the signal transduction involved in actions of 15(R/S)-methyl-LXA(4). Mesangioproliferative nephritis was induced by a single intravenous injection of the mouse monoclonal anti-Thy1.1 antibodies. The nephritic rats were treated by intravenous injection of 15(R/S)-methyl-LXA(4) every 8h until the rats were sacrificed. There were increments in glomerular infiltration of leukocytes, expressions of protein and mRNA of interleukin (IL)-1beta and IL-6, activities of nuclear factor-kappaB (NF-kappaB) in nephritic rats from day 1 to 4 after induction of nephritis. The enhanced proteinuria, proliferation score of mesangial cells, glomerular proliferating cell nuclear antigen (PCNA) positive cells, activities of phosphorylated phosphoinositide 3-kinase (PI3-K), Akt(1), alpha-smooth muscle actin (alpha-SMA) and signal transducer and activator of transcription 3(STAT(3)), and reduced expression of p27(kip1) were found on day 4 after induction of nephritis. Treatment of nephritic rats with 15(R/S)-methyl-LXA(4) significantly reduced the protenuria, glomerular infiltration of leukocyte, expressions of protein and mRNA of IL-1beta and IL-6, proliferation score of mesangial cells, glomerular PCNA positive cells, activities of phosphorylated PI3-K, Akt(1), alpha-SMA, NF-kappaB and STAT(3), and ameliorated the decrement in p27(kip1) induced by anti-Thy1.1 antibodies. Protective effects of 15(R/S)-methyl-LXA(4) on nephritis induced by anti-Thy1.1 antibodies were related to PI3-K/Akt(1)/p27(kip1)/cyclin pathway, STAT(3) and NF-kappaB pathway-dependent signal transduction.

Prognostic and predictive value of serum carcinoembryonic antigen levels in advanced non-small cell lung cancer patients with epidermal growth factor receptor sensitive mutations and receiving tyrosine kinase inhibitors.

BACKGROUND: Despite the widespread use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced or recurrent non-small cell lung cancer (NSCLC), no biomarkers for predicting the efficacy of EGFR-TKIs in patients with EGFR-sensitive mutations have yet been identified. The purpose of our study was to explore the effect of baseline serum tumor markers in stage IIIB/IV NSCLC patients treated with EGFR-TKIs. METHODS: One hundred and seventy-seven patients with stage IIIB/IV NSCLC who harbored EGFR-sensitive mutations and were treated with EGFR-TKIs were retrospectively reviewed. Their levels of CEA, CYFRA 21-1, NSE and CA199 were measured before treatment with EGFR-TKIs. RESULTS: The response rate for all patients was 54.8%, with a median progression-free survival of 6.6 months and overall survival of 14.8 months. In univariate analyses, patients with CEA levels below the cutoff point (10 ng/ml) had higher RR, better PFS, and better OS than those with CEA levels above 10 ng/mL (RR: 69.2% vs. 43.4%, p= 0.001; mPFS: 7.8 months vs. 5.3 months, p=0.029; mOS: 18.8 months vs. 11.8 months, p=0.000). The baseline serum CEA level was an independent factor for RR (odds ratio [OR] =0.322, p=0.001), PFS (hazard ratio [HR] =1.45, p=0.025), and OS (HR=2.133, p=0.000). CONCLUSION: Our study suggests that baseline serum CEA levels may play a role in predicting the efficacy of EGFR-TKIs in stage IIIB/IV NSCLC patients with EGFR-sensitive mutations who are treated with EGFR-TKIs.