子宫内膜异位症患者血清VEGF和CRP水平变化及其相关性

目的：探讨子宫内膜异位症患者血清血管内皮生长因子（VEGF）和C-反应蛋白（CRP）的水平变化及其相关性。方法：采用ELISA的方法测定30例III～Ⅳ期子宫内膜异位症患者（其中增生期13例、分泌期17例）和22例非子宫内膜异位症患者（其中增生期10例、分泌期12例）血清VEGF和CRP的水平,并分析两者相关性。结果：子宫内膜异位症组分泌期血清VEGF水平明显高于对照组（P〈0．05）;子宫内膜异位症组增生期血清CRP水平明显高于对照组（P〈0．05）;子宫内膜异位症组增生期和分泌期血清VEGF与CRP水平存在显著的正相关（F0．52,P〈0．05;r=0．44,P〈0．05）。结论：子宫内膜异位症患者血清VEGF、CRP水平的升高说明了过度血管生成和异常炎症反应是子宫内膜异位症的显著特征。     

Serum levels of angiogenic cytokines in systemic lupus erythematosus and their correlation with disease activity

We investigated the serum concentration of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) using an enzyme-linked immunosorbent assay (ELISA) in a group of 60 patients with systemic lupus erythematosus (SLE), and 20 healthy controls. We also examined the possible association between the serum concentrations of these factors and certain clinical, laboratory parameters and SLE activity. HGF, VEGF and TGF-beta1 were detectable in all patients with SLE, and in all normal individuals. bFGF was measurable in 70% of the patients with SLE and in 65% of the healthy controls. The HGF level was higher in active SLE (median 1,019.5pg/ml) than in inactive SLE (median 787.8 pg/ml) (p < 0.005) or in the control group (median 847.0 pg/ml) (p < 0.009). The level of VEGF in active SLE was also higher (203.5 pg/ml) than in inactive disease (116.1 pg/ml) (p < 0.05) or in healthy persons (133.5 pg/ml) (p < 0.04). The levels of bFGF and TGF-beta1 were similar for both the active and inactive SLE, and the control group (p > 0.05). We found a significant, positive correlation between the levels of HGF and bFGF (r = 0.268, p < 0.04), HGF and TGF-beta1 (r = 0.365, p < 0.005) and HGF and VEGF (r = 0.327, p < 0.02) as well as VEGF and TGF-beta1 (r = 0.543, p < 0.001). We found a positive correlation between VEGF serum levels and platelet counts (r = 0.272, p < 0.04), and the TGF-beta1 concentration and platelet count (r = 0.313; p < 0.02). There was also a positive correlation between HGF serum concentration and the SLE activity score (r = 0.435, p < 0.001), as well as between the level of VEGF and SLE activity (r = 0.252, p = 0.05). In conclusion, serum levels of the angiogenic factors HGF and VEGF may be relevant in SLE pathogenesis. Their concentrations seem to be markers of SLE activity.     

Serum heat shock protein 27 levels in patients with hepatocellular carcinoma

Levels of serum heat shock protein 27 (sHsp27) have been studied in numerous cancer types, but their potential relevance in patients with hepatocellular carcinoma (HCC) is undetermined. Our aim was to compare sHsp27 levels in patients with HCC and HCC-free controls. Specifically, we recruited 71 patients with HCC (80 % with early tumour), 80 patients with chronic liver disease (59 with liver cirrhosis and 21 with chronic active hepatitis) and 42 healthy subjects. sHsp27 was measured by immunoenzymatic assay. Results showed that sHsp27 levels were significantly (p < 0.001) higher in patients with HCC than in the other groups, particularly in those with hepatitis C virus (HCV)-related disease. In HCC patients, sHsp27 levels were not associated with prognostic risk factors, such as size/multiplicity of nodules and stage. In logistic regression analysis, performed in patients with liver disease, log-sHsp27 was associated with a significant age-adjusted 2.5-fold increased odds ratio of HCC and with a significant 4.4-fold higher odds ratio of HCC in the subgroup with HCV-related liver disease. In receiver operating characteristic curve analysis, sensitivity and specificity of the best sHsp27 cut-off value (456.5 pg/ml) for differentiating patients with HCC from those with HCC-free chronic liver disease were 70 and 73 %, respectively. In conclusion, sHsp27 levels are enhanced in patients with HCC and may represent a candidate biomarker of HCC.     

Radiotherapy for locally advanced head and neck cancer in elderly patients: results and prognostic factors a single cohort

BackgroundThe objective of this study was to assess the treatment outcomes and prognostic factors of elderly patients with locally advanced head and neck cancer (LAHNC) undergoing radiotherapy (RT).Materials and methodsA retrospective cohort from a single institution, from 2000 to 2015, including patients older than 65 years old with LAHNC (stage III–IVa) treated by RT combined or not with chemotherapy (CRT). Univariate and multivariate analysis (MVA) were performed to identify prognostic factors associated with overall survival (OS), cancer-specific survival (CS), and locoregional control (LRC). A p-value < 0.05 was considered significant.Results220 patients with LAHNC and > 65 years of age were identified. The median follow-up was 3.8 years, the 3/5 years estimated OS, CS, and LRC rate was 40%/30%, 49%/34%, 76%/45%, respectively. In the univariate analysis, clinical stage (III vs. IVa/b, p = 0.01), tumor stage (T1/2 vs. T3/4, p = 0.035), Karnofsky performance status (KPS, 60–70, p = 0.03) and tumor site (other than vs. hypopharynx, p = 0.0001) were associated with lower OS. Patients with clinical stage (III vs. IVa/b, p = 0.01), tumor stage (T1/2 vs. T3/4, p = 0.015), N stage (N0/1 vs. N2/3, p = 0.04), (KPS 60–70, p = 0.04) and tumor site (other than vs. hypopharynx, p = 0.0001) had worst CS. For the LRC, clinical stage (III vs. IVa/b, p = 0.02), tumor stage (T1/2 vs. T3/4, p = 0.02), treatment type (CRT vs. RT, p = 0.02), RT technique (IMRT vs. 2DRT/3DRT, p = 0.0001), and tumor site (other than vs. hypopharynx, p = 0.02) were significant. In the MVA, KPS maintained significant for OS and CS. For LRC, clinical stage (Iva/b, p = 0.007), tumor stage (T3/4, p = 0.047) and radiotherapy technique other than IMRT (p = 0.0001) were significant.ConclusionThe OS, CS, and LRC were associated with several prognostic factors. The clinical performance was the main marker of OS and CS. Chemoradiation should be offered to selected elderly patients using IMRT to improve LRC.     

Molecular prognostic prediction for locally advanced nasopharyngeal carcinoma by support vector machine integrated approach

Background

Accurate prognostication of locally advanced nasopharyngeal carcinoma (NPC) will benefit patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm based on support vector machine (SVM) through integrating the expression levels of multi-biomarkers.

Methodology/Principal Findings

Ninety-seven locally advanced NPC patients in a randomized controlled trial (RCT), consisting of 48 cases serving as training set and 49 cases as testing set of SVM models, with 5-year follow-up were studied. We designed SVM models by selecting the variables from 38 tissue molecular biomarkers, which represent 6 tumorigenesis signaling pathways, and 3 EBV-related serological biomarkers. We designed 3 SVM models to refine prognosis of NPC with 5-year follow-up. The SVM1 displayed highly predictive sensitivity (sensitivity, specificity were 88.0% and 81.9%, respectively) by integrating the expression of 7 molecular biomarkers. The SVM2 model showed highly predictive specificity (sensitivity, specificity were 84.0% and 94.5%, respectively) by grouping the expression level of 12 molecular biomarkers and 3 EBV-related serological biomarkers. The SVM3 model, constructed by combination SVM1 with SVM2, displayed a high predictive capacity (sensitivity, specificity were 88.0% and 90.3%, respectively). We found that 3 SVM models had strong power in classification of prognosis. Moreover, Cox multivariate regression analysis confirmed these 3 SVM models were all the significant independent prognostic model for overall survival in testing set and overall patients.

Conclusions/Significance

Our SVM prognostic models designed in the RCT displayed strong power in refining patient prognosis for locally advanced NPC, potentially directing future target therapy against the related signaling pathways.     

Glycine inhibits angiogenic signaling in human hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is a highly vascularized tumor with limited susceptibility to chemotherapy. Modern targeted therapies are aimed at specific properties of this neoplasm. Glycine is a simple non-essential amino acid with potential antiangiogenic effects. In this study, the amino acid’s effect on angiogenic signaling in an in vitro model of HCC was evaluated. HepG2 and Huh7 cells were treated with glycine-free DMEM supplemented with 0, 0.01, 0.1, 1.0, 2.0, 5.0 and 10 mM glycine. The direct effects of glycine on the viability of HCC cells were monitored using MTT assay. To detect angiogenic signaling, mRNA and protein levels of vascular endothelial growth factor (VEGF-A) were measured using RT-PCR and Western Blot assays. To determine whether or not glycine receptors (GlyR) played a significant role, the specific antagonist, strychnine, was used as a direct inhibitor. Western Blotting was performed to show the presence of GlyR. While there was no direct pro- or antiproliferative effect of either glycine or strychnine in both cell lines, glycine was shown to significantly decrease VEGF-A expression on mRNA and protein level up to 63 % in both cell lines. This effect was blunted by the presence of strychnine. GlyR was also identified in both cell lines. Glycine decreases GlyR-dependent, VEGF-A-mediated, angiogenic signaling in human HCC and thus might be a promising additive to chemotherapy treatment strategies for highly vascularized tumors.     

Treatment outcomes in locally advanced colorectal carcinoma

BACKGROUND: Locally advanced colorectal cancers form a distinct subgroup where contiguous organs could be involved without distant metastases and so may be amenable to curative surgical resection. It was our objective to report our experience in treating six such patients with operable locally advanced colorectal carcinomas. METHODS: We retrospectively reviewed the case notes of 47 patients who were diagnosed with colorectal cancers at M S Ramaiah Medical Teaching Hospital between the years 1996 - 2001. Six patients were identified with T4 lesions, adjacent organ involvement and with no nodal involvement. The treatments and outcomes for these patients were then reviewed. RESULTS: Two of three patients with rectal malignancies who underwent pelvic exenteration succumbed to disease recurrence within the first 18 months. One of the three patients with colonic cancers died of non malignant causes. The other two are disease free till date. CONCLUSIONS: Aggressive multivisceral resections for locally advanced colonic cancers might be appropriate. Rectal cancers when locally advanced may be considered for pelvic exenteration, but a more guarded prognosis may apply.     

Pretreatment hemoglobin level as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma

AimEvaluate pretreatment hemoglobin values as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy.BackgroundAnemia is one of the most prevalent laboratory abnormalities in oncological disease. It leads to a decrease in cellular oxygen supply, altering radiosensitivity of tumor cells and compromising therapeutic outcomes.Materials and MethodsRetrospective evaluation of patients with HNSCC treated with cCRT. Primary and secondary endpoint was to evaluate the correlation of Hb levels (≥12.5 g/dL or <12.5 g/dL) at the beginning of cCRT with overall survival (OS) and progression-free survival (PFS), respectively.ResultsA total of 108 patients were identified. With a median follow-up of 16.10 months median OS was 59.70 months for Hb ≥12.5 g/dL vs. 14.13 months for Hb <12.5 g/dL (p = 0.004). PFS was 12.29 months for Hb ≥12.5 g/dL and 1.68 months for Hb <12.5 g/dL (p = 0.016).ConclusionsIn this analysis, Hb ≥12.5 g/dL correlated with significantly better OS and PFS. Further studies are needed to validate these findings.     

Serum levels of FAK and some of its effectors in adult AML: correlation with prognostic factors and survival

Focal adhesion kinase (FAK), human myofibrillogenesis regulator-1 (MR-1), ephrin receptor type A4 (EphA4), proto-oncogene tyrosine kinase Src (Src), and protein kinase C (PKC) are important markers in proliferation, survival, and migration in some cancers. However, the significance of each is still unclear in different malignancies, including acute myeloid leukemia (AML). Therefore, this study was conducted to investigate their serum levels in Egyptian adult de novo AML patients (n?=?70) against healthy volunteers (n?=?20). We managed to study the correlation between each pair and to investigate their association with diagnosis, prognosis, and survival. Serum levels were analyzed using enzyme-linked immunosorbent assay (ELISA). We found that FAK, MR-1, Src, and PKC serum levels were significantly higher in AML patients compared to control (p?<?0.0001), and this was associated with significantly lower EphA4 level (p?<?0.0001). Interestingly, we also observed a significant negative correlation of FAK (p?=?0.027), MR-1 (p?=?0.003), Src (p?=?0.038), and PKC (p?=?0.03) with patients’ overall survival (OS) while there was a positive significant correlation between EphA4 and OS (p?=?0.007). In conclusion, this study suggests that FAK, MR-1, EphA4, Src, and PKC may be used as early diagnostic and prognostic markers with high sensitivity and specificity in AML patients and thus may be incorporated into the patients’ early diagnostic and prognostic panels.

     

Clinical applications of angiogenic growth factors and their inhibitors

Promoting the formation of new collateral vessels in ischemic tissues using angiogenic growth factors (therapeutic angiogenesis) is a an exciting frontier of cardiovascular medicine. Conversely, inhibition of the action of key regulators of angiogenesis, such as VEGF, constitutes a promising approach for the treatment of solid tumors and intraocular neovascular syndromes. These concepts are being tested now in clinical trials.     

Differential expression levels of urokinase-type plasminogen activator and cathepsin D in locally advanced laryngeal squamous cell carcinoma: clinical implications

The expression levels and the prognostic impact of urokinase-type plasminogen activator (uPA) and cathepsin D (CD) were evaluated in patients with locally advanced laryngeal squamous cell carcinoma (LSCC). uPA and CD protein levels were determined by immunoluminometric or immunoenzymatic assays in the cytosol of paired sets of tumor tissues and corresponding adjacent normal mucosa (NLM) from 57 patients with stage III/IV LSCC and were correlated with a number of clinicobiological parameters of this tumor including anatomical site, tumor grade, nodal status, clinical stage, DNA ploidy, proliferation rate, and patient outcome. Median uPA levels were significantly higher in LSCC than in NLM (1.8 ng/mg of protein vs 0.3 ng/mg; p<0.001) whereas median CD levels were not significantly increased in tumor tissue compared to NLM (24 pmol/mg vs 19 pmol/mg, p=0.063). No significant correlation was observed between uPA and CD concentrations in tumor tissues (r=-0.1; p=0.4). Furthermore, the distribution analysis of uPA and CD in tumors showed no correlation between expression levels of these proteinases and the parameters mentioned above including patient outcome. However, when data were matched according to each parameter examined it was observed that the differences in uPA content between LSCC and NLM, expressed as uPA tumor/normal tissue ratio (T/M), were more marked in clinically advanced and/or aggressive forms of LSCC (i.e., node positive, stage IV, poorly and moderately differentated, aneuploid multiclonal, low S-phase, subglottis tumors). These data suggest that in such tumors altered regulation of uPA may occur to a greater extent than in less aggressive and less advanced forms of LSCC. This phenomenon was not observed for CD. However, in tumors with a high proliferation rate, in stage IV tumors as well as in those located in the supraglottis, CD levels were significantly higher than those found in the corresponding NLM (p=0.008, p=0.02 and p=0.03, respectively). In conclusion, uPA is highly expressed in locally advanced LSCC and appears to be implicated in some key events of progression of this tumor such as local invasion and/or nodal involvement, whereas CD does not seem to have a role in promoting these processes. Nevetheless, neither of these proteinases seem to be prognostically useful in patients with stage III/IV tumors.     

Diagnostic and prognostic value of circular RNAs in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumour, which has posed a heavy health and financial burden worldwide. Due to limited symptoms at the early stage and the limitation in current biomarkers, HCC patients are usually diagnosed at the advanced stage with a pessimistic overall survival rate. Circular RNAs (circRNAs) are a subclass of single-stranded RNAs characterized by a covalently closed loop structure without 3’- or 5’-end. With advances in high-throughput sequencing technology and bioinformatics, accumulating studies have demonstrated the promotor or suppressor roles of circRNAs in the carcinogenesis, progression, and metastasis of HCC. Moreover, circRNAs are characteristic of higher abundance, stability and conservation compared with linear RNAs. Therefore, circRNAs have emerged as one of the most promising diagnostic and prognostic biomarkers for HCC with reliable accuracy, sensitivity and specificity. In this review, we briefly introduce the characteristics of circRNAs and summarize the roles of circRNAs in the biological procedures of HCC. Furthermore, we provide an overview on the potential diagnostic and prognostic value of circRNAs as biomarkers for patients with HCC. Finally, we discuss future perspectives of circRNAs in cancer research.     

Serum levels of tumor necrosis factor alpha correlate with response to neoadjuvant chemotherapy in locally advanced breast cancer

It has been shown that serum levels of tumor necrosis factor alpha (TNF-alpha) are increased in breast cancer patients. There are few data available on the reduction of serum levels of this cytokine following chemotherapy. The aim of this study was to determine the effect of neoadjuvant chemotherapy on serum concentrations of TNF-alpha and the relation to response rates in locally advanced breast cancer. Twenty consecutive patients with non-inflammatory stage III-B breast cancer achieving a partial or complete clinical response to three courses of neoadjuvant chemotherapy followed by modified radical mastectomy were prospectively included in the study and evaluated. Sera were collected before the start and after the termination of chemotherapy. Serum concentrations of TNF-alpha were measured by an ELISA method. The pathological response rates were also evaluated and recorded. The control group consisted of 12 healthy age-matched women. The mean pre-treatment TNF-alpha value of breast cancer patients was 15.9 +/- 0.9 pg/mL while it was 5.8 +/- 1.7 pg/mL in the control group; the difference was statistically significant (p < 0.0001). The serum levels of TNF-alpha were markedly decreased in patients with partial and complete responses compared to pre-treatment values (p < 0.0001). There was also a difference in TNF-alpha levels in patients with partial vs complete responses (p < 0.0001). The relative change between pre- and post-treatment values correlated significantly with the type of response (p = 0.004). These results suggest that the serum concentration of TNF-alpha can be an indicator of response and could be used in clinical decision-making for patients with locally advanced breast cancer.     

Identification of postoperative prognostic microRNA predictors in hepatocellular carcinoma

Comparison of microRNA (miRNA) expression profiles in the noncancerous liver tissues adjacent to hepatocelluar carcinomas (HCCs) was a strategy to identify postoperative prognostic predictors in this study. Expression profiles of 270 miRNAs were determined in the paraneoplastic liver tissues of 12 HCC patients with known postoperative prognosis. A panel of candidate miRNA predictors was identified. The prognostic predictive value of these candidate miRNAs was then verified in 216 postoperative HCC patients. Univariate analysis identified 8 and 3 miRNA predictors for recurrence-free (RFS) and overall (OS) survivals, respectively. Multivariate analysis revealed high expression levels of miR-155 (HR, 2.002 [1.324-3.027]; P?=?.001), miR-15a (HR, 0.478 [0.248-0.920]; P?=?.027), miR-432 (HR, 1.816 [1.203-2.740]; P?=?.015), miR-486-3p (HR, 0.543 [0.330-0.893]; P?=?.016), miR-15b (HR, 1.074 [1.002-1.152]; P?=?.043) and miR-30b (HR, 1.102 [1.025-1.185]; P?=?.009) were significantly associated with RFS. When clinicopathological predictors were included, multivariate analysis revealed that tumor number and miR-432, miR-486-3p, and miR-30b expression levels remained significant as independent predictors for RFS. Additionally, expression knockdown of miR-155 in J7 and Mahlavu hepatoma cells resulted in decreased cell growth and enhanced cell death in xenograft tumors, suggesting an oncogenic effect of miR-155. In conclusion, significant prognostic miRNA predictors were identified through examination of miRNA expression levels in paraneoplastic liver tissues. Functional analysis of a miRNA predictor, miR-155, suggested that the prognostic miRNA predictors identified under this strategy could serve as potential molecular targets for anticancer therapy.     

Development of a preoperative prognostic scoring system to predict benefits of hepatic resection in advanced hepatocellular carcinoma patients

Objective: The present study aimed to identify risk factors for overall survival in advanced hepatocellular carcinoma (HCC) patients and establish a scoring system to select patients who would benefit from hepatic resection.Methods: Survival curves were analyzed using the Kaplan–Meier method and log-rank test. The prognostic scoring system was developed from training cohort using a Cox-regression model and validated in a external validation cohortResults: There were 401 patients in the training cohort, 163 patients in the external validation cohorts. The training cohort median survival in all patients was 12 ± 1.07 months, rate of overall survival was 49.6% at 1 year, 25.0% at 3 years, and 18.0% at 5 years. A prognostic scoring system was established based on age, body mass index, alkaline phosphatase, tumor number and tumor capsule. Patients were classified as low- risk group(≤3.5) or high-risk group(>3.5). High-risk patients had a median survival of 9 months, compared with 23 months in low-risk patients. The area under the receiver operating characteristic curve (AUC) of the prognostic scoring system was 0.747 (0.694–0.801), which is significantly better than AFP, Child-Pugh and ALBI. The AUC of validation cohorts was 0.716 (0.63–0.803).Conclusion: A prognostic scoring system for hepatic resection in advanced HCC patients has been developed based entirely on preoperative variables. Patients classified as low risk using this system may experience better prognosis after hepatic resection.