Serine metabolism in macrophage polarization.

OBJECTIVE: Emerging studies have revealed that macrophages possess different dependences on the uptake, synthesis, and metabolism of serine for their activation and functionalization, necessitating our insight into how serine availability and utilization impact macrophage activation and inflammatory responses. METHODS: This article summarizes the reports published domestically and internationally about the serine uptake, synthesis, and metabolic flux by the macrophages polarizing with distinct stimuli and under different pathologic conditions, and particularly analyzes how altered serine metabolism rewires the metabolic behaviors of polarizing macrophages and their genetic and epigenetic reprogramming. RESULTS: Macrophages dynamically change serine metabolism to orchestrate their anabolism, redox balance, mitochondrial function, epigenetics, and post-translation modification, and thus match the distinct needs for both classical and alternative activation. CONCLUSION: Serine metabolism coordinates multiple metabolic pathways to tailor macrophage polarization and their responses to different pathogenic attacks and thus holds the potential as therapeutic target for types of acute and chronic inflammatory diseases.

LncRNA-H19 gene plays a significant role in regulating glioma cell function.

BACKGROUND: Glioma is an aggressive adult primary cancer, and is characterized by low cure rate, poor prognosis, and high recurrence. The present study aimed to investigate the effect of lncRNA-H19 gene silencing on glioma cell function. METHODS: lncRNA-H19 interference vector (LV3-si-H19) and negative control vector (LV3-NC) were stably transfected into U251 and U87-MG cells, respectively. Quantitative real-time PCR (qRT-PCR) was performed to investigate the expression of lncRNA-H19. Cell proliferation capacity was tested by adopting cell counting kit (CCK8), and propidium iodide (PI) was used for cell cycle analysis. Meanwhile, flow cytometry (FCM) method was used to investigate cell apoptosis, cell migration capacity was detected via wound healing and transwell experiments, and sphere-forming ability was examined in serum-free suspension culture. Additionally, glioma animal models were conducted through injecting U251 cells to estimate the effects of lncRNA-H19 on glioma growth in vivo. RESULTS: Knocking down lncRNA-H19 gene could effectively suppress the proliferation of U251 and U87-MG cells. The knockdown of lncRNA-H19 remarkably inhibited the migration and blocked cycle progressions of U251 and U87-MG cells, yet, no obvious changes were observed in cell apoptosis. Besides, inhibiting lncRNA-H19 expression could attenuate sphere-forming function of U251 and U87-MG cells. Additionally, tumor volume and weight were significantly reduced in rats injected with U251 LV-si-H19 cell line compared to untransfected and negative controls, when survival time was obviously prolonged in U251 LV-si-H19 injection groups. CONCLUSION: LncRNA-H19 gene plays a carcinogenic role in glioma progression via enhancing aggressive behavior of glioma cells.

Maximal tumor diameter in the preoperative tumor magnetic resonance imaging (MRI) T2 image is associated with prognosis of Grade II Glioma.

ABSTRACT: Factors associated with the prognosis of low-grade glioma remain undefined. In this study, we examined whether the maximal tumor diameter in the preoperative tumor magnetic resonance imaging (MRI) T2 image is associated with the prognosis of grade II gliomas patients, aiming to provide insights into the clinical prediction of patient outcome.We retrospectively analyzed the clinical data of patients with Grade II glioma, who were hospitalized in Xiangya Hospital, Central South University, from 2011 to 2016. Kaplan-Meier and Cox proportional hazards analyses were performed to determine the association between maximal tumor diameter and prognosis.A total of 90 patients with grade II glioma were included in this study. Mean patient age was 37.7 ±â€Š13.0 years, and 58.9% of them were male. Kaplan-Meier survival analysis of overall survival (overall survival [OS], P = .009) and event-free survival (EFS, P = .002) revealed statistically significant differences between the patients with lesion diameter <7 cm and those with lesion diameter ≥7 cm. The maximal tumor diameter in the preoperative tumor MRI T2 image was identified as a prognostic factor of OS (P = .013), while constituting an independent risk factor for EFS (P = .002) alongside elevated histological grade after recurrence (P = .006).The maximal tumor diameter in the preoperative tumor MRI T2 image independently predicts OS and EFS in patients with grade II glioma.

Preoperative Neutrophil/Lymphocyte Ratio Is an Independent Prognostic Biomarker in Patients with Low-Grade Gliomas.

BACKGROUND: There are no standardized criteria to predict the prognosis of patients with low-grade gliomas. Therefore, novel prognostic biomarkers that can guide follow-up schedules and therapeutic approaches urgently are required in patients with low-grade gliomas. METHODS: One hundred nineteen patients with World Health Organization (WHO) II gliomas were recruited between January 2010 and December 2016 from Xiangya Hospital for this study. We collected neutrophil and lymphocyte values from the full blood counts measured 24 h before surgery. Neutrophil-to-lymphocyte ratios (NLRs) were then calculated. The significance of the NLR was determined based on a nonparametric test. The Kaplan-Meier method was used to estimate survival rates. The influence of the NLR on progression-free survival and overall survival was evaluated using univariate and multivariate Cox proportional hazards models. RESULTS: Preoperative NLRs were upregulated in patients with WHO II gliomas who relapsed or died. Preoperative NLRs were also significantly correlated with age, preoperative neutrophil values, and preoperative lymphocyte values. Compared with the low preoperative NLR group, patients with WHO II gliomas in the high preoperative NLR group had significantly higher relapse and lower survival rates. In addition, the preoperative NLR and tumor type were independent prognostic parameters of progression-free survival for WHO II gliomas, whereas only the preoperative NLR was an independent prognostic parameter of overall survival for WHO II gliomas. CONCLUSIONS: High preoperative NLRs were significantly associated with greater relapse and poor prognosis in patients with WHO II gliomas.

Prognostic value of magnetic resonance imaging features in low-grade gliomas.

Introduction: The treatment strategy for low-grade gliomas (LGGs) is still controversial, and there are no standardized criteria to predict the prognosis of patients with LGGs. Magnetic resonance imaging (MRI) is a routine test for preoperative diagnosis for LGG and can reflect the destructive features for the tumor. In the present study, we aimed to explore the relationship between the MRI features and prognosis in patients with LGG.Methods: Clinical data of 80 patients with pathologically proved LGGs between January 2010 and December 2016 were analyzed retrospectively. MRI features were classified as contrast enhancement pattern (focal enhancement, diffuse enhancement and ring-like enhancement), necrosis and cysts based on the preoperative MR images. Kaplan-Meier method and multivariate analysis were performed on the data by SPSS software to explore the prognostic significance of MRI features.Results: Patients with cystic LGG had a significantly longer 5-year progression-free survival (PFS) than that with no cyst (90.9 ± 8.7 vs 65.7 ± 9.1%, P=0.045). Multivariate analysis further verified cyst as an independent prognosis factor for PFS (P=0.027, hazard ratio [HR] = 0.084). Additionally, patients with ring-like enhancement exhibited significantly longer 5-year PFS time in the Kaplan-Meier survival curves (100 vs 67.2 ± 7.7%, P=0.049). There was no significant difference in PFS and overall survival (OS) between patients with or without necrosis.Conclusion: Our study suggests that cyst formation and ring-like enhancement on preoperative MR images can be useful to predict a favorable prognosis in patients with LGGs.

Dosimetric Comparisons of Volumetric Modulated Arc Therapy and Tomotherapy for Early T-Stage Nasopharyngeal Carcinoma.

PURPOSE: To compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in treating early T-stage nasopharyngeal carcinoma (NPC). METHOD: Ten patients with early T-stage NPC who received tomotherapy using simultaneously integrated boost (SIB) strategies were replanned with VMAT (RapidArc of Varian, dual-arc). Dosimetric comparisons between the RapidArc plan and the HT plan included the following: (1) D98, homogeneity, and conformity of PTVs; (2) sparing of organs at risk (OARs); (3) delivery time and monitor units (MUs). RESULTS: (1) Compared with RapidArc, HT achieved better dose conformity (CI of PGTVnx + nd: 0.861 versus 0.818, P = 0.004). (2) In terms of OAR protection, RapidArc exhibited significant superiority in sparing ipsilateral optic nerve (Dmax: 27.5Gy versus 49.1Gy, P < 0.001; D2: 23.5Gy versus 48.2Gy, P < 0.001), contralateral optic nerve (Dmax: 30.4Gy versus 49.2Gy, P < 0.001; D2: 26.2Gy versus 48.1Gy, P < 0.001), and optic chiasm (Dmax: 32.8Gy versus 48.3Gy, P < 0.001; D2: 30Gy versus 47.6Gy, P < 0.001). HT demonstrated a superior ability to protect the brain stem (D1cc: 43.0Gy versus 45.2Gy, P = 0.012), ipsilateral temporal lobe (Dmax 64.5Gy versus 66.4 Gy, P = 0.015), contralateral temporal lobe (Dmax: 62.8Gy versus 65.1Gy, P = 0.001), ipsilateral lens (Dmax: 4.27Gy versus 5.24Gy, P = 0.009; D2: 4.00Gy versus 5.05Gy, P = 0.002; Dmean: 2.99Gy versus 4.31Gy, P < 0.001), contralateral lens (Dmax: 4.25Gy versus 5.09Gy, P = 0.047; D2: 3.91Gy versus 4.92Gy, P = 0.005; Dmean: 2.91Gy versus 4.18Gy, P < 0.001), ipsilateral parotid (Dmean: 36.4Gy versus 41.1Gy, P = 0.002; V30Gy: 54.8% versus 70.4%, P = 0.009), and contralateral parotid (Dmean: 33.4Gy versus 39.1Gy, P < 0.001; V30Gy: 48.2% versus 67.3%, P = 0.005). There were no statistically significant differences in spinal cord or pituitary protection between the RapidArc plan and the HT plan. (3) RapidArc achieved a much shorter delivery time (3.8 min versus 7.5 min, P < 0.001) and a lower MU (618MUs versus 5646MUs, P < 0.001). CONCLUSION: Our results show that RapidArc and HT are comparable in D98, dose homogeneity, and protection of the spinal cord and pituitary gland. RapidArc performs better in shortening delivery time, lowering MUs, and sparing the optic nerve and optic chiasm. HT is superior in dose conformity and protection of the brain stem, temporal lobe, lens, and parotid.

Prognostic analysis of patients with locally advanced nasopharyngeal carcinoma following intensity modulated radiation therapy.

The present study retrospectively analyzed the prognostic factors of 135 patients with locally advanced nasopharyngeal carcinoma (NPC) who received intensity modulated radiation therapy between August 2008 and January 2012 at Xiangya Hospital of Central South University. Patients were staged from III-IVA according to the 7th American Joint Committee on Cancer staging system. Using Statistical Analysis System 9.3 software, the present study demonstrated that, among these 135 patients, the 5-year overall survival, the 5-year local relapse-free survival, and the 5-year disease metastasis-free survival were 84, 82, and 78%, respectively. Multivariate Cox regression analysis identified that targeted treatment [hazard ratio (95% confidence interval), 2.642 (1.001, 6.972); P=0.0497] served as an independent negative prognostic factor in locally advanced NPC. The results of immunostaining revealed that the staining intensity of the radiation-resistant group was increased compared with that of the radiation-sensitive group. These results demonstrate that a high expression of EGFR may be associated with radiation resistance, and targeted treatment may not be effective in patients with locally advanced nasopharyngeal carcinoma with low expression of EGFR.

Nimotuzumab combined with concurrent chemoradiotherapy benefits patients with advanced nasopharyngeal carcinoma.

BACKGROUND: The potential benefits and possible risks associated with combined nimotuzumab and concurrent chemoradiotherapy in patients with advanced nasopharyngeal carcinoma (NPC) have yet to be determined. METHODS: The databases PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang were systematically searched through February 2017 for studies comparing combined nimotuzumab and chemoradiotherapy versus chemoradiotherapy alone in the treatment of NPC. Primary outcomes were complete and partial responses, and the secondary outcome was adverse reactions. The random-effect model was used to pool relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Nine randomized control trials and six cohort studies were included in the final analysis (n=1,015 patients). Compared with chemoradiotherapy alone, chemoradiotherapy combined with nimotuzumab was associated with an increased response rate (RR =1.11, 95% CI: 1.01-1.22). Combined treatment further reduced the occurrence rate of erythropenia (RR =0.11, 95% CI: 0.05-0.28) and neutropenia (RR =0.12, 95% CI: 0.05-0.27). The differences in the rates of other complications were not significant. CONCLUSION: Nimotuzumab combined with concurrent chemoradiotherapy is more effective in patients with advanced NPC than chemoradiotherapy alone. Patients receiving combination therapy did not have a higher rate of adverse reactions. Nimotuzumab can thus be recommended as an adjunct therapy in patients with advanced NPC.

High expression of Ki-67 acts a poor prognosis indicator in locally advanced nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy in Southern China and Southeast Asia compared with Western countries. The standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to satisfactory treatment, it can cause local recurrence and distant metastases in some patients after treatment by radiation. We retrospectively reviewed 108 NPC patients (7th AJCC Ⅲ-Ⅳa) who have received intensity modulated radiation therapy (IMRT) between August 2008 and January 2012 at Xiangya Hospital of Central South University. Ninety-eight patients with >60% reduction of tumor size after radiation treatment were regarded as radiation sensitive, Ten patients with <40% reduction of tumor size after radiation treatment were regarded as radiation resistant. Using immunohistochemistry, we found that the high expression rate of Ki-67 in radiation resistant and radiation sensitive patients was 80.0% and 42.6%, respectively, and the difference was statistically significant (p = 0.025). The 5-year progress free survival rates in patients with low and high expression of Ki-67 was 70.7% and 48.0%, respectively, and the difference was statistically significant (p = 0.0008). Multivariate Cox regression analysis identified that high expression of Ki-67 was an independent negative prognostic factor in nasopharyngeal carcinoma patients [Hazard ratio (95% CI), 2.098(1.101, 3.996); p = 0.024]. These results demonstrate that high expression of Ki-67 contributes to radiation resistance and acts a poor prognosis indicator in patients with locally advanced nasopharyngeal carcinoma.

Mean cerebral blood volume is an effective diagnostic index of recurrent and radiation injury in glioma patients: A meta-analysis of diagnostic test.

We conducted a meta-analysis to evaluate the diagnostic values of mean cerebral blood volume for recurrent and radiation injury in glioma patients. We performed systematic electronic searches for eligible study up to August 8, 2016. Bivariate mixed effects models were used to estimate the combined sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, diagnostic odds ratios and their 95% confidence intervals (CIs). Fifteen studies with a total number of 576 participants were enrolled. The pooled sensitivity and specificity of diagnostic were 0.88 (95%CI: 0.82-0.92) and 0.85 (95%CI: 0.68-0.93). The pooled positive likelihood ratio is 5.73 (95%CI: 2.56-12.81), negative likelihood ratio is 0.15 (95%CI: 0.10-0.22), and the diagnostic odds ratio is 39.34 (95%CI:13.96-110.84). The summary receiver operator characteristic is 0.91 (95%CI: 0.88-0.93). However, the Deek's plot suggested publication bias may exist (t=2.30, P=0.039). Mean cerebral blood volume measurement methods seems to be very sensitive and highly specific to differentiate recurrent and radiation injury in glioma patients. The results should be interpreted with caution because of the potential bias.

Prognostic value and predictive threshold of tumor volume for patients with locally advanced nasopharyngeal carcinoma receiving intensity-modulated radiotherapy.

BACKGROUND: Gross target volume of primary tumor (GTV-P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity-modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to find a suitable cut-off value of GTV-P for prognosis prediction. METHODS: Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver operating characteristic (ROC) curves were used to identify the cut-off values of GTV-P for the prediction of different endpoints [overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS)] and to test the prognostic value of GTV-P when compared with that of the American Joint Committee on Cancer T staging system. RESULTS: The 358 patients with locally advanced NPC were divided into two groups by the cut-off value of GTV-P as determined using ROC curves: 219 (61.2%) patients with GTV-P ≤46.4 mL and 139 (38.8%) with GTV-P >46.4 mL. The 3-year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV-P ≤46.4 mL than in those with GTV-P > 46.4 mL (all P < 0.05). Multivariate analysis indicated that GTV-P >46.4 mL was an independent unfavorable prognostic factor for patient survival. The ROC curve verified that the predictive ability of GTV-P was superior to that of T category (P < 0.001). The cut-off values of GTV-P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4 mL, respectively. CONCLUSION: In patients with locally advanced NPC, GTV-P >46.4 mL is an independent unfavorable prognostic indicator for survival after IMRT, with a prognostic value superior to that of T category.

Growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency: A meta-analysis.

The risk of growth hormone on cancer in adult with growth hormone deficiency remains unclear. We carried out a meta-analysis to evaluate the risk of cancer in adult with and without growth hormone replacement therapy. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases up to 31 July 2016 for eligible studies. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models if appropriate. The Newcastle-Ottawa Scale was used to assess the study quality. Two retrospective and seven prospective studies with a total of 11191 participants were included in the final analysis. The results from fixed-effects model showed this therapy was associated with the deceased risk of cancer in adult with growth hormone deficiency (RR=0.69, 95%CI: 0.59-0.82), with low heterogeneity within studies (I2=39.0%, P=0.108). We performed sensitivity analyses by sequentially omitting one study each time, and the pooled RRs did not materially change, indicating that our results were statistically stable. Begger's and Egger's tests suggested that there was no publication bias (Z=-0.63, P=0.520; t=0.16, P=0.874). Our study suggests that growth hormone replacement therapy could reduce risk of cancer in adult with growth hormone deficiency.

HK2 is a radiation resistant and independent negative prognostic factor for patients with locally advanced cervical squamous cell carcinoma.

The mechanism by which overexpression of hexokinase 2 (HK2) indicates locally advanced cervical squamous cell carcinoma (LACSCC) with radio-resistance is still unknown despite being an independent biomarker of poor prognosis. Here, we retrospectively analyzed 132 female patients receiving radiotherapy for cervical squamous cell carcinoma including 85 radiation-sensitive cases and 47 radiation-resistant cases. The expression of HK2 was examined by immunohistochemistry. The percentage of high HK2 expression in the radiation-resistant group differed from the radiation-sensitive group with statistical significance (P < 0.001) even if divided into three subgroups including a lower 5-year progression free survival group (PFS) for comparison (P < 0.001). The Kaplan Meier curve analysis showed that there were differences between the two groups (P < 0.001). Therefore, this study proves a close relationship between HK2 expression and radio-resistance. Multivariate Cox regression analysis implied that HK2 was an independent prognostic indicator of cervical squamous carcinoma (HR (95% CI), 2.940 (1.609, 1.609); P = 0.002).

High expression of PKM2 as a poor prognosis indicator is associated with radiation resistance in cervical cancer.

Our study aimed to investigate the association of Pyruvate Kinase isozyme type M2 (PKM2) with radiation resistance in locally advanced cervical squamous cell carcinoma (LACSCC). We retrospectively reviewed 132 female patients who received primary radiation therapy to treat LACSCC at Federation Internationale of Gynecologie and Obstetrigue (FIGO) stages IB-IVA. Forty-seven patients with progression free survival (PFS) of less than 36 months were regarded to have radiation resistance. Eighty-five patients with PFS no less than 36 months were regarded as radiation sensitive. Using immunohistochemistry, we found that the overexpression rate of PKM2 in radiation resistant and radiation sensitive patients was 87.2% and 57.6%, respectively, and the difference was statistically significant (p<0.001). The 5-year progress free survival rates in patients with low and high expression of PKM2 was 80.4% and 60.5%, respectively, and the difference was statistically significant (p=0.008). Multivariate Cox regression analysis identified that high expression of PKM2 is an independent negative prognostic factor in cervical cancer patients [Hazard ratio (95% CI), 2.888 (1.347, 6.194) p=0.006]. These results demonstrate that overexpression of PKM2 contributes to radiation resistance and acts a poor prognosis indicator in patients with LACSCC.

Aberrant expression of osteopontin and E-cadherin indicates radiation resistance and poor prognosis for patients with cervical carcinoma.

Radiotherapy is the first-line treatment for all stages of cervical cancer, whether it is used for radical or palliative therapy. However, radioresistance of cervical cancer remains a major therapeutic problem. Consequently, we explored if E-cadherin (a marker of epithelial-mesenchymal transition) and osteopontin could predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). Patients were retrospectively reviewed and 111 patients divided into two groups (radiation-resistant and radiation-sensitive groups) according to progression-free survival (PFS). In pretreated paraffin-embedded tissues, we evaluated E-cadherin and osteopontin expression using immunohistochemical staining. The percentage of patients with high osteopontin but low E-cadherin expression in the radiation-resistant group was significantly higher than those in the radiation-sensitive group (p<0.001). These patients also had a lower 5-year PFS rate (p<0.001). Our research suggests that high osteopontin but low E-cadherin expression can be considered as a negative, independent prognostic factor in patients with LACSCC ([Hazard ratios (95% CI) 6.766 (2.940, 15.572)], p<0.001).

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

High Expression of SOX2 and OCT4 Indicates Radiation Resistance and an Independent Negative Prognosis in Cervical Squamous Cell Carcinoma.

Radiotherapy (RT) as a preoperative or postoperative adjuvant or primary treatment is the most common management modality for locally advanced cervical cancer. Radioresistance of tumor cells remains a major therapeutic problem. Consequently, we aimed to explore if the stem cell biomarkers SOX2 and OCT4 protein could be used to predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). These 132 patients were divided into two groups (radiation-resistant and radiation-sensitive groups) according to progress-free survival (PFS). Using pretreatment paraffin-embedded tissues, we evaluated SOX2 and OCT4 expression using immunohistochemical staining. The percentage of overexpression of SOX2 and OCT4 in the radiation-resistant group was much higher than that in the radiation-sensitive group (p<0.001 and p <0.001, respectively). The patients with high expression of SOX2 and OCT4 showed a shorter PFS than those with low expression. Our study suggests that the expression of SOX2 and OCT4 in tumor cells indicates resistance to radiotherapy and that these two factors were important predictors of poor survival in patients with LACSCC (hazard ratio [95% CI], 2.294 [1.013, 5.195] and 2.300 [1.050, 5.037], respectively; p=0.046 and p=0.037, respectively).

ZNF569, a novel KRAB-containing zinc finger protein, suppresses MAPK signaling pathway.

Transcription factors play an essential role in altering gene expression. A great progress about transcription factors has been made towards the understanding of normal physiological processes, embryonic development, and human diseases. Here we report the identification and characterization of a novel KRAB-containing zinc-finger protein, ZNF569, which is isolated from a human embryonic heart cDNA library. ZNF569 encodes a putative protein of 686 amino acids. The protein is conserved across different species during evolution. Expression of ZNF569 was found in most of the examined human adult and embryonic tissues with a higher level in heart and skeletal muscles. The KRAB and ZNF motifs of ZNF569 represent potent repression domains. When ZNF569 is fused to Gal-4 DNA-binding domain and co-transfected with VP-16, ZNF569 protein suppresses transcriptional activity. Overexpression of ZNF569 in COS-7 cells inhibited the transcriptional activities of SRE and AP-1, which may be silenced by siRNA. The results suggest that ZNF569 protein may act as a transcriptional repressor that suppresses MAPK signaling pathway to mediate cellular functions.

A novel KRAB zinc-finger protein, ZNF480, expresses in human heart and activates transcriptional activities of AP-1 and SRE.

The zinc-finger motif found in many transcription factors is thought to be important for human heart development and diseases. In this study, we have identified and characterized a novel zinc-finger gene named ZNF480 using degenerate primers from an early human embryo heart cDNA library. ZNF480 contains a KRAB-A box and 12 C2H2 zinc fingers. The cDNA sequence contains an open reading frame of 1551 bp, encoding a putative protein of 516 amino acid residues with a predicted molecular mass of 57 kDa. Northern blot analysis indicates that a 4.7kb transcript specific for ZNF480 is expressed only in embryonic heart. In the adult tissues, the expression of ZNF480 is restricted largely to heart, skeletal muscle, pancreas, and placenta. Overexpression of ZNF480 in cells activates the transcriptional activities of AP-1 and SRE. Therefore, our data suggest that ZNF480 may act as a positive regulator in MAPK-mediated signaling pathways that lead to the activation of AP-1 and SRE.