[Clinical study of percutaneous vertebroplasty combined with (125)I seeds implantation in the treatment of patients with thoracic metastatic tumor complicated with posterior vertebral defect].

Objective: To analyze the safety and efficacy of percutaneous vertebroplasty combined with interstitial implantation (125)I of seeds (PVPI) in the treatment of thoracic vertebroplasty with posterior vertebra defect. Methods: A retrospective analysis of the clinical data of 64 patients with thoracic spine metastases admitted to Yunnan Cancer Hospital from November 2017 to May 2019 was conducted, including 32 patients with posterior vertebra defect (experimental group) and 32 cases without (control group). Forty-two vertebral bodies of 32 patients in the experimental group were treated with improved PVPI surgery, which performed with the secondary sealing method and inclined puncture needle injection bone cement rotary filling technology, to reduce leakage. The 54 vertebral bodies of 32 patients in control group underwent PVPI. The two groups of patients were followed up on the second day, one month, three months and six months after the operation, and the short-term efficacy, long-term efficacy and safety indicators of the two groups were compared. Results: All 64 patients successfully completed the surgical treatment. The visual analogue scores and Karnofsky scores of the experimental group and the control group were improved to varying degrees on the second day, 1 month, 3 months and 6 months after the operation. There was no statistically significant difference between the two groups (P>0.05). The amount of bone cement in the experimental group and control group was (2.36±0.20) ml and (2.39±0.17) ml, and the difference was not statistically significant (P=0.482). The amount of (125)I seed implantation was (30.63±0.91) and (32.56±0.68), respectively, the difference was not statistically significant (P=0.925). The partial response rates of the study group and the control group were 81.3% and 87.5%, the stable disease rates were 12.5% and 9.4%, the differences were not statistically significant (P>0.05). The median overall survival (mOS) of the study group was 13 months, and the median progression-free survival (mPFS) was 8 months. The mOS of the control group was 14 months, and the mPFS was 8 months. The differences were not statistically significant (P>0.05). In the experimental group, 6 (14.3%) vertebral bodies had cement leakage, of which 2 (4.8%) were cement leakage at posterior vertebra, 4 (9.5%) were paravertebral cement leakage. Seven (13.0%) paravertebral cement leakage occurred in the control group. There was no significant difference in bone cement leakage between the two groups (P=0.097). Bone cement leakage in both groups did not cause serious complications such as spinal cord injury and paraplegia. Conclusion: The application of PVPI in the treatment of thoracic metastatic tumor patients with posterior vertebra defect can acquire better clinical efficacy and safety through conduction of the improved intraoperative technology and paying more attention to the control of bone cement distribution and other issues.

LmCDA1 organizes the cuticle by chitin deacetylation in Locusta migratoria.

Cells produce an extracellular matrix (ECM) with a stereotypic organization that is important for tissue function. The insect cuticle is a layered ECM that mainly consists of the polysaccharide chitin and associated proteins adopting a quasi-crystalline structure. Our understanding of the molecular mechanisms deployed during construction of the highly ordered protein-chitin ECM so far is limited. In this study, we report on the role of the chitin deacetylase 1 (LmCDA1) in the organization of the protein-chitin ECM in the migratory locust Locusta migratoria, and LmCDA1 localizes predominantly to the apical tier of the protein-chitin ECM, but it is also found in lower regions. Reduction of LmCDA1 function correlates with lower amounts of chitin and impedes conversion of chitin to chitosan by deacetylation. Establishment of the quasi-crystalline architecture of the protein-chitin ECM is, however, independent of LmCDA1 activity, but it is dependent on another chitin deacetylase, LmCDA2, which has no detectable effects on chitin deacetylation and, as shown previously, no influence on chitin content. Our data reveal that LmCDA1 and LmCDA2 act in parallel and independently from each other in defining the dimensions of the cuticle. Both enzymes are non-uniformly distributed within the protein-chitin matrix, suggesting a site-autonomous function.

[Clinical significance of syndecan-1 and syndecan-2 expression in gallbladder squamous cell/adenosquamous carcinoma and adenocarcinoma].

Objective: To investigate the expression of syndecan-1 and syndecan-2 and their clinicopathological significance in patients with gallbladder squamous cell (SC)/adenosquamous carcinoma (ASC) and adenocarcinoma (AC). Methods: A total of 126 patients with SC/ASC (n=46) and AC (n=80) were included in this study. The expression levels of syndecan-1 and syndecan-2 were detected by Envison™ immunohistochemistry assay. The clinical and prognostic significance of syndecan-1 and syndecan-2 were analyzed. Results: In the 46 SC/ASC samples, syndecan-1 and syndecan-2 were positively expressed in 29 (63.0%) and 28 (60.9%) tumor tissues, respectively. (Positive expression was defined based on the staining in the component of squamous cell carcinoma. That is to say, the tissue which adenocarcinoma part was positively stained, but squamous cell carcinoma part was negatively stained is also regarded as negative.) In the 80 AC samples, 47 (58.8%) cases showed syndecan-1 positive expression, and 51 (63.8%) showed syndecan-2 positive expression. There was no significant difference in the positive rates of syndecan-1 and syndecan-2 between SC/ASC and AC groups (P>0.05 for all). The levels of syndecan-1 and syndecan-2 were associated with tumor size, TNM staging, lymph node metastasis, invasion of adjacent tissue, and surgical procedures in SC/ASC patients (P<0.05 for all). However, their expression was associated with tumor differentiation, tumor size, TNM staging, lymph node metastasis, invasion of adjacent tissue, and surgical procedures in AC patients (P<0.05 for all). The Kaplan-Meier survival analysis of SC/ASC and AC patients revealed that the average survival time for patients with positive syndecan-1 and syndecan-2 expression was significantly shorter than that of those with negative expression (P<0.01 for all). Cox multivariate analysis indicated that syndecan-1 and syndecan-2 expression were independent unfavorable prognostic factors for SC/ASC and AC patients (P<0.05 for all). Conclusion: The syndecan-1 and syndecan-2 expression are associated with the tumor progression and poor prognosis in patients with gallbladder SC/ASC and AC.

Effects of human parathyroid hormone on bone morphogenetic protein signal pathway following spinal fusion in diabetic rats.

Osteoporosis is a major complication in patients with diabetes mellitus. Thus, it is crucial to study the signal mechanisms responsible for enhancement of bone mass in diabetes. Administration of human parathyroid hormone (hPTH) has been reported to prevent osteoblast apoptosis and have anabolic effects on bone in animals and humans. In the present study, we examined the effects of hPTH on expression of bone morphogenetic protein type 2 (BMP-2) and its receptor BMPR2 in diabetic rats following spinal fusion. Our data show that hPTH amplified BMP-2 and BMPR2 in bone tissues of non-diabetic rats, but not in diabetic rats. Our data further demonstrate that hPTH plays a role in regulating BMP-2 and BMPR2 via mTOR-PI3K signal pathway. We suggest specific signaling pathways by which hPTH regulates BMP-2 via mTOR-PI3K mechanism in bone formation following spinal fusion. Notably, our data indicate under diabetic conditions this signal pathway is impaired, thereby likely affecting bone formation after spinal fusion. The subsequent induction of BMP-2 and BMPR2 are likely a part of the protective effects aimed at attenuating pathological bone damage as a result of diabetes.

Pinning effect of reactive elements on adhesion energy and adhesive strength of incoherent Al2O3/NiAl interface.

The profound effects of reactive elements (REs) on the adhesion energy and adhesive strength of the α-Al2O3/ß-NiAl interface in thermal barrier coating (TBC) systems have attracted increasing attention because RE-doping has played a significant role in improving the thermal cycling lifetime of TBCs. However, the fundamental mechanism is, so far, not well understood due to the experimental difficulty and theoretical complexity in interface modelling. For this purpose, in the present study we have performed comprehensive density functional theory calculations and information targeted experiments to underline the origin of the surprising enhancement of interface adhesion, stability and mechanical strength of the α-Al2O3/ß-NiAl interface by different RE doping levels. Our results suggest that the interface failure firstly appears within the NiAl layer adjacent to the Al-terminated oxide under mechanical loading, while the formation of O-RE-Ni bond pairs at the interface can effectively hinder the interface de-cohesion, providing a higher mechanical strength. By comparing several typical REs, it is observed that Hf can emerge not only with the highest interface adhesion energy, but also the highest mechanical strength; in agreement with our experimental results. By continuously increasing the dopant concentration, the strengthening effect may increase correspondingly, but is limited by the solute solubility. These results shed light into the effect of REs on the stability and strength of the α-Al2O3/ß-NiAl interface, providing theoretical guidance for interface design via a combinational analysis of bond topology and electronic structure.

Comparative study of clinicopathological significance, BIRC7, and STC2 expression between squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder.

Gallbladder cancers (GBCs) are uncommon, but highly aggressive cancers. The majority of GBCs are adenocarcinomas (ACs), but rare subtypes of GBCs such as squamous cell carcinoma (SC) and adenosquamous carcinoma (ASC) are observed as well. The clinicopathological characteristics of SC/ASC have not been well documented. Expressions of BIRC7 and STC2 were observed in some tumors. However, BIRC7 and STC2 expressions and clinical significances in gallbladder cancer have not been reported.In this study, the protein expressions of BIRC7 and STC2 in 46 SCs/ASCs and 80 ACs were measured using immunohistochemistry. We demonstrated that positive BIRC7 and STC2 expressions were significantly associated with large tumor mass (>3cm), high TNM stage and lymph node metastasis in SC/ASC and AC (p<0.05). Positive expression of BIRC7 was significantly associated with invasion of around tissues and organs in both SC/ASC and AC. Additionally, negative BIRC7 and STC2 expressions were significantly associated with surgical curability in AC. Univariate Kaplan-Meier analysis showed that BIRC7 and STC2 expressions, differentiation, tumor size, TNM stages, invasion, lymph node metastasis, and surgical curability were significantly associated with post-operative survival in both SC/ASC and AC patients(p < 0.001). Multivariate Cox regression analysis showed that positive BIRC7 and STC2 expressions are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive BIRC7 and STC2 expressions are closely correlated with clinical, pathological, and biological behaviors as well as poor-prognosis of gallbladder cancer.

IL-17RA aptamer-mediated repression of IL-6 inhibits synovium inflammation in a murine model of osteoarthritis.

OBJECTIVE: Generate DNA aptamers to inhibit IL-17RA-mediated synovial inflammation in an experimental mouse model of osteoarthritis (OA). METHODS: A novel cell-SELEX method was applied to obtain DNA aptamers specific for IL-17RA. A single-stranded (ss) DNA library with four(30) probes was synthesised. By incubating this library with NIH3T3 cells, we collected DNA ligands that could bind the cell surface. The collected ligands were incubated with IL-17RA-deficient NIH3T3 cells, and unbound ssDNA was harvested from the supernatant for the next round of selection. After 12 cycles, specific aptamers against IL-17RA were generated. For animal experiments, a meniscectomy was performed on Balb/C mice to generate an animal model of OA. Mice received weekly intra-articular (i.a.) injections of aptamers or control treatments for 6 weeks. Synovial membranes were evaluated by histomorphology and the mRNAs of critical inflammatory cytokines were measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: An aptamer termed RA10-6 was obtained that could efficiently block IL-17 binding to IL-17RA in a dose-dependent manner in vitro. Histological examination and quantitative RT-PCR results showed that OA mice that injected with RA10-6, especially in combination with celecoxib demonstrated inhibition of synovial thickening and reduction in IL-6 levels in the synovial tissue. CONCLUSION: Our results suggest that RA10-6 can inhibit synovial inflammation by blocking IL-17/IL-17RA-mediated IL-6 expression. RA10-6 acted synergistically with celecoxib to inhibit IL-6 expression in synovial tissues. Thus, aptamers targeting IL-17RA might serve as potent adjunctive agents for the early treatment of OA.

Association of ATP1A1 gene polymorphism with heat tolerance traits in dairy cattle.

Heat stress produces oxidative stress and affects the alternation of plasma K(+) and Na(+). Since Na(+),K(+)-ATPase is sensitive to oxidative stress and critical for maintaining the homeostasis of these two ions, we examined the genetic polymorphism of the ATP1A1 gene in 160 Holstein cows using polymerase chain reaction low ionic strength single-strand conformation polymorphism and DNA sequencing methods. G to A at position -14103 in exon 14 and C to T at position -14242 in intron 14 of the bovine ATP1A1 gene were identified, but the former single nucleotide polymorphism was silent with respect to the amino acid sequence of the protein. However, we found significant correlations between ATP1A1 gene polymorphism and the coefficient of heat tolerance (P<0.01) and with respiratory rate (P<0.01). Genotype AC was the most favorable genotype for heat tolerance. This polymorphism site has potential as a genetic marker for heat tolerance traits in dairy cattle breeding.

[Effect and mechanism of low-dose chidamide on the treatment of primary immune thrombocytopenia].

Objective: To explore the effect and mechanism of low-dose chidamide on the treatment of primary immune thrombocytopenia (ITP) . Methods: Passive ITP animal model and active ITP animal model were established by C57BL/6J mice. Different doses of chidamide (0, 0.01, 0.1, 0.5, and 5 mg/kg) were orally administrated twice a week for 120 hours in passive ITP mice. Secondly, low-dose chidamine (0.1 mg/kg) was given intragastrically administrated twice a week in active ITP mice. The platelet counts in the peripheral blood before and after treatment were detected. Four weeks later, mice were executed to prepare splenocyte suspension; natural regulatory T cells (CD4(+)CD25(+)Foxp3(+) nTreg cells) in splenocyte suspension were detected by flow cytometry. Serum IL-6 was measured by ELISA. Peripheral blood mononuclear cells from ITP patients were co-cultured with low-dose chidamide in vitro. After incubation for 72 hours, CD4(+)CD25(+)Foxp3(+) Treg cells of mononuclear cells was detected. CD4(+)CD25(+) Treg cells and CD4(+)CD25(-) effector T cells were separated by immunomagnetic beads. The Treg cells and effector T cells were co cultured in a ratio of 1∶4, and treated with low-dose chidamide. The proliferation of effector T cells was detected. Results: Chidamide with low dose (0.1 mg/kg) significantly improved platelet counts in passive ITP mouse model, as well as in the ITP active mouse model and reduced the mortality related to bleeding. Low-dose chidamide significantly increased the number and proportion of nTreg cells in mouse splenocytes, and decreased serum IL-6 level in active ITP mice. In ITP patients, low-dose chidamide also significantly expanded Treg cells in the PBMC culture system. Besides, the proliferation of effector T cells was suppressed. Conclusion: Low-dose chidamide enhances the proliferation of CD4(+)CD25(+)Foxp3(+) regulatory T cells to mediate immunosuppressive function. Serum IL-6 is inhibited for further immune tolerance. In vivo animal study suggestes that low-dose chidamide has a novel therapeutic effect on ITP.

Contraception and induced abortions for women of reproductive age married in recent years in rural areas of Shandong, China.

BACKGROUND: In 2001, the Chinese Government published the Population and Family Planning Law which gave citizens the right to know the facts about, and to choose, methods of birth control. Since then, the percentage use of different contraceptive methods has changed. More and more women have been using male condoms for birth control, which has resulted in an increasing prevalence of induced abortions of unintended pregnancies in recent years. OBJECTIVE: To investigate the relationship between choice of contraception methods and rates of induced abortion in the rural areas of Shandong. MATERIALS AND METHODS: A questionnaire-based survey on contraceptive methods and abortions in women of reproductive age who married between January 1, 2002, and August 31, 2005, was carried out in 8 sampling communities of rural areas in Shandong Province. RESULTS: 7,159 of 8,520 women of childbearing age took part in the survey, which gave a response rate of 84.0%. The accumulative abortion rate was 2.39% for intrauterine device (IUD) use and 5.46% for male condom use during the period of survey. A longer duration of marriage and a longer time of male condom use increased the rate of induced abortions, while longer periods of IUD use decreased the rate of induced abortions. CONCLUSION: The results indicated that an integrated program for family planning, especially one that better educates condom users, must be initiated in the rural areas of Shandong Province, China.

[Application of robot-assisted surgery in the surgical treatment of head and neck cancer].

In recent years, robot-assisted surgery (RAS) has developed rapidly and become one of the hot topics in clinical research. Compared with traditional surgery, RAS has advantages in terms of minimal invasiveness, aesthetics, and functional preservation, and has been gradually applied in clinical practice such as neurosurgery, urology, and head and neck surgery. In the treatment of head and neck tumors, RAS can effectively minimize the surgical injury and accelerate postoperative recovery. This article reviews the application of RAS in the resection of primary lesions of head and neck tumors, neck dissection, and reconstruction of tissue defects.

Baseline concentrations and spatial distribution of trace metals in surface soils of Guangdong province, China.

A total of 260 surface soil samples were collected to investigate the spatial distribution of trace metals in Guangdong province, one of the fast developing regions in China. The results show that the upper baseline concentrations of Cu, Pb, Zn, Cd, Ni, Cr, and Hg were 28.7, 57.6, 77.8, 0.13, 23.5, 87.0, and 0.15 mg kg(-1), respectively. Regional parent materials and pedogenesis are the primary factors influencing the concentrations of trace metals, and various anthropogenic activities are the second most important factors. The spatial distribution of trace metals is correlated to the geological characters with high concentrations of trace metals always located in regional fault areas, basins, and the Pearl River Delta alluvial plain and to the low concentrations associated with the other areas in Guangdong province.

Physiological dissection revealed that both uptake and assimilation are the major components regulating different growth responses of two tobacco cultivars to nitrogen nutrition.

K326 and HD represent major tobacco cultivars in China, which required large N fertiliser input but at different application rates. To understand primary components affecting tobacco N use physiology, we adopted these two varieties as valuable genetic material to assess their growth response to N nutrition. We established a hydroponic culture system to grow plants supplied with different N regimes. Plant biomass, N, ammonium, nitrate, arginine, GS and NR activity, N transfer and use efficiency as well as root uptake were examined. Our data revealed the preference of K326 and HD to utilise nitrate or ammonium nitrate but not ammonium alone, with 2 mm N supply probably sufficient and economical to achieve good biomass production at the vegetative stage. Moreover, both varieties were very sensitive to ammonium, perhaps due to lack of or abnormal signalling related to nitrate and/or arginine rather than impairment of N acquisition and initial assimilation; this was supported by measurements of the plant content of N, ammonium and activities of GS and NR. Notably, short-term 15 N root influx studies identified differential uptake kinetics of K326 and HD, with distinct affinities and transport rates for ammonium and nitrate. The data suggest that the growth adaptation of K326 or HD to higher or lower N may be ascribed to different competences for effective N uptake/translocation and assimilation. Thus, our work provides valuable information to prompt deeper investigation of the molecular basis controlling plant N use efficiency.

A hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo expansion of human corneal epithelial stem cells.

PurposeTo develop a hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo cultivation of human corneal epithelial stem cells (CESCs).Patients and MethodsCESCs were cultivated from donor limbal explants on the HyStem-C Hydrogel bio-scaffold in 12-well plates for 3 weeks. Group A used the traditional supplemented hormonal epidermal medium (SHEM) and group B used the defined SHEM (without fetal bovine serum and toxin A, adding 20% serum replacement). The growth and morphology of the cultured cells were assessed by phase contrast microscope. The expressions of specific cell markers were assessed by immunofluorescence staining and quantitative real-time PCR (qRT-PCR).ResultsSuccessful cultures of CESCs were obtained in both groups, resulting in multilayered stratified epithelia. Comparing to group A, the cells in group B was grown slightly slower and formed less cellular layers at the end of culture. The corneal specific cytokeratin (K) 12 and differentiation markers, involucrin, and connexin 43, were mainly expressed in the superficial cellular layers in both groups. Interestingly, certain basal cells were immune-positive to proposed stem cell markers such as K19, ABCG2, and integrin ß1 in both groups. There was no significant difference between the two groups with regard to the gene expression levels of all these selected corneal markers (all P>0.05).ConclusionsThe hyaluronan hydrogel scaffold-based xeno-free culture system may support the expansion of regenerative CESCs without the risk of xeno component contamination. The regenerated epithelium maintains similar characteristics of native corneal epithelium.

shRNA-mediated silencing of hTERT suppresses proliferation and promotes apoptosis in osteosarcoma cells.

In this study, we aim to explore the effects of short hairpin RNAs (shRNAs) targeting human telomerase reverse transcriptase (hTERT) on the proliferation and apoptosis of osteosarcoma cells. After the synthesis of shRNA that target hTERT, osteosarcoma cells were assigned into three experimental groups-shRNA group, scramble group and blank group. The transcription and expressions of the hTERT gene in transfected cells were measured with quantitative real-time polymerase chain reaction and western blotting. Cell proliferation in each group was detected by Cell Counting Kit-8 assay. Cell cycle and rates of apoptosis were measured by flow cytometry. Expressions of apoptosis-related proteins, caspase-9 and caspase-3, were detected by western blotting. Telomerase activity was measured by PCR enzyme-linked immunosorbent assay. Results show that both the mRNA and protein expressions of hTERT were significantly lowered after the transfection of hTERT-shRNA. The proliferation capacity of transfected osteosarcoma MG-63, SaOS2 and U2OS cells in the shRNA group was lower than that in the blank group. We also found changes and differences in the amount of cells throughout the cell cycle. All cells in the G0/G1 phase increased in numbers, whereas the number of cells in the S phase were reduced, with elevated apoptosis rates. Expressions of apoptosis-related proteins, caspase-9 and caspase-3, were increased and telomerase activity was decreased in the transfected shRNA group (all P<0.05). Our results showed that shRNA targeting of the hTERT gene was able to inhibit cell proliferation and promote apoptosis of osteosarcoma cells by reducing the telomerase activity.

Spatial distribution and vertical variation of arsenic in Guangdong soil profiles, China.

Total of 260 soil profiles were reported to investigate the arsenic spatial distribution and vertical variation in Guangdong province. The arsenic concentration followed an approximately lognormal distribution. The arsenic geometric mean concentration of 10.4 mg/kg is higher than that of China. An upper baseline concentration of 23.4 mg/kg was estimated for surface soils. The influence of soil properties on arsenic concentration was not important. Arsenic spatial distributions presented similar patterns that high arsenic concentration mainly located in limestone, and sandshale areas, indicating that soil arsenic distribution was dependent on bedrock properties than anthropogenic inputs. Moreover, from A- to C-horizon arsenic geometric mean concentrations had an increasing tendency of 10.4, 10.7 to 11.3 mg/kg. This vertical variation may be related to the lower soil organic matter and soil degradation and erosion. Consequently, the soil arsenic export into surface and groundwaters would reach 1040 t year-1 in the study area.

PAKs in Human Cancer Progression: From Inception to Cancer Therapeutic to Future Oncobiology.

Since the initial recognition of a mechanistic role of p21-activated kinase 1 (PAK1) in breast cancer invasion, PAK1 has emerged as one of the widely overexpressed or hyperactivated kinases in human cancer at-large, allowing the PAK family to make in-roads in cancer biology, tumorigenesis, and cancer therapeutics. Much of our current understanding of the PAK family in cancer progression relates to a central role of the PAK family in the integration of cancer-promoting signals from cell membrane receptors as well as function as a key nexus-modifier of complex, cytoplasmic signaling network. Another core aspect of PAK signaling that highlights its importance in cancer progression is through PAK's central role in the cross talk with signaling and interacting proteins, as well as PAK's position as a key player in the phosphorylation of effector substrates to engage downstream components that ultimately leads to the development cancerous phenotypes. Here we provide a comprehensive review of the recent advances in PAK cancer research and its downstream substrates in the context of invasion, nuclear signaling and localization, gene expression, and DNA damage response. We discuss how a deeper understanding of PAK1's pathobiology over the years has widened research interest to the PAK family and human cancer, and positioning the PAK family as a promising cancer therapeutic target either alone or in combination with other therapies. With many landmark findings and leaps in the progress of PAK cancer research since the infancy of this field nearly 20 years ago, we also discuss postulated advances in the coming decade as the PAK family continues to shape the future of oncobiology.

Epigenomic regulation of oncogenesis by chromatin remodeling.

Disruption of the intricate gene expression program represents one of major driving factors for the development, progression and maintenance of human cancer, and is often associated with acquired therapeutic resistance. At the molecular level, cancerous phenotypes are the outcome of cellular functions of critical genes, regulatory interactions of histones and chromatin remodeling complexes in response to dynamic and persistent upstream signals. A large body of genetic and biochemical evidence suggests that the chromatin remodelers integrate the extracellular and cytoplasmic signals to control gene activity. Consequently, widespread dysregulation of chromatin remodelers and the resulting inappropriate expression of regulatory genes, together, lead to oncogenesis. We summarize the recent developments and current state of the dysregulation of the chromatin remodeling components as the driving mechanism underlying the growth and progression of human tumors. Because chromatin remodelers, modifying enzymes and protein-protein interactions participate in interpreting the epigenetic code, selective chromatin remodelers and bromodomains have emerged as new frontiers for pharmacological intervention to develop future anti-cancer strategies to be used either as single-agent or in combination therapies with chemotherapeutics or radiotherapy.

[Mutant Rad50 enhances killing effects of radiation on nasopharyngeal carcinoma cell line CNE1].

Objective: To investigate the killing effects of radiation and mutant Rad50 transfection on human nasopharyngeal carcinoma cell line CNE1. Methods: The experimental groups included: control group, Ad-Rad50-GFP group, Ad-EGFP group, irradiation group, Ad-Rad50-GFP combined with irradiation group, and Ad-EGFP combined with irradiation group. CNE1 cells were transfected with recombinant adenoviral vector Ad-Rad50-GFP carrying mutant Rad50 gene. The expressions of Mre11, Rad50, Nbs1, and relevant constituents composing MRN complex were detected by Western Blot. Neutral comet assay was used to detect the effect of mutant Rad50 on restoration process of DNA damage. Cell growth curve was used to evaluate the growth inhibition of CNE1 by mutant Rad50 and radiation. Results: Expressions of Mre11, Rad50, and Nbs1 in cells of Ad-Rad50-GFP group were less significantly than those in control group when irradiation was completed (0.48 vs 0.62, 0.42 vs 0.5, and 0.53 vs 0.69, respectively, P<0.05) and 24 hours after irradiation (0.41 vs 0.69, 0.46 vs 0.58, and 0.34 vs 0.78, respectively, P<0.05). The mean tail moment (MTM) in Ad-Rad50-GFP plus irradiation group was higher than that in irradiation group when irradiation was completed (16.06 vs 14.8, P<0.05), 24 hours after irradiation (58.23 vs 15.89, P<0.05) and 48 hours after irradiation: (45.12 vs 11.42, P<0.05). Seven days after irradiation, the cells in Ad-Rad50-GFP plus irradiation group was less than those in control group or irradiation group (both P<0.05). Conclusion: Mutant Rad50 enhances killing effects of radiation on nasopharyngeal carcinoma cell line CNE1.

Differential regulation of cytokine and receptor transcript expression in human corneal and limbal fibroblasts by epidermal growth factor, transforming growth factor-alpha, platelet-derived growth factor B, and interleukin-1 beta.

PURPOSE: To explore further the significance of three patterns of cytokine dialogues that have been characterized between human corneal and limbal epithelial cells and fibroblasts. METHODS: Northern hybridization of the transcript expression of type I cytokine receptors (EGFR, IL-1R, and PDGFR-beta), type II cytokines (bFGF, LIF, and TGF-beta 1), and type III cytokines (HGF and KGF) by human corneal and limbal fibroblasts was conducted under the modulation of TGF-alpha, PDGF-BB, IL-1 beta, and EGF (type I cytokines). The mechanism of upregulation by IL-1 beta was studied further with respect to proto-oncogene expression and under the treatment of cycloheximide and actinomycin D. RESULTS: Results showed that EGF upregulated LIF and HGF but downregulated KGF and M-CSF. Unlike EGF, TGF-alpha upregulated additional EGFR, PDGFR-beta, bFGF, and TGF-beta 1, suggesting that although they share the same EGFR, TGF-alpha, which is produced by epithelium, is more effective in activating fibroblasts than EGF, which is present in tears. The upregulation of PDGF-BB was similar to that of TGF-alpha, except that it further stimulated IL-8, supporting their synergistic roles in promoting wound healing. Uniquely, IL-1 beta upregulated KGF expression by limbal fibroblasts more than corneal fibroblasts and IL-8 and M-CSF expression, but it downregulated PDGFR-beta. In IL-1 beta, the upregulation of cytokines and receptors was preceded by the upregulation of c-fos, c-jun, and c-myc, and it was inhibited by actinomycin D. Its upregulation of LIF was superinduced, but the upregulation of bFGF and KGF was inhibited, and that of the rest was not affected by cycloheximide. CONCLUSIONS: These findings suggest that epithelial cells under stress or injury (producing IL-1) might preferentially activate limbal epithelial stem cells indirectly by fibroblasts and simultaneously might promote inflammation during wound healing.