Radiotherapy and adjuvant chemotherapy have become the standard treatments for multiple types of cancer. Although cancer cells are usually sensitive to radiotherapy, metastasis and local failure ...still occur mainly due to developed resistance to radiotherapy. Thus, it is critical to improve therapeutics for cancer treatment. The present study demonstrated that third-generation bisphosphonate zoledronic acid (ZOL), even at a low concentration, augments the radiosensitivity of cancer cells exposed to ionizing radiation (IR) by inducing S-phase arrest and subsequently promoting apoptosis. This function of ZOL was associated with elevated levels of cyclin A and cyclin B in the S and M phases, as well as decreased p21CIP1 expression. In addition, ZOL also inhibited malignant the invasiveness of cancer cells. Notably, these effects could be enhanced concurrently with IR. The present data indicated that combined treatment with ZOL plus IR may be a novel technique to augment the radiosensitivity of cancer cells.
Esophageal squamous cell carcinoma (ESCC) has a low 5-year patient survival rate. Radiotherapy, as a preoperative or postoperative treatment of surgery, has a crucial role in improving local control ...and survival of ESCC. Various chemotherapeutic and biologic agents have been used as radio-sensitizers in combination with radiotherapy. Here, we demonstrate that zoledronic acid (ZOL) has a radio-sensitizing effect on ESCC cells. Exposure of ESCC cancer cells to ZOL plus radiation resulted in increased cell death through arresting the cell cycle between S and G2/M phases. ZOL appeared to inhibit proliferation, tube formation and invasion of endothelial cells. These anti-angiogenetic effects were more marked concurrently with irradiation. In addition, synergistic suppressive effects on VEGF expression were observed after combined treatment. Our data suggest that the combination of ZOL and radiation is a promising therapeutic strategy to enhance radiation therapy for ESCC patients.
Background
Previous studies have shown a down-regulation of the gene encoding cyclin-dependent kinase 10 (CDK10) in hepatocellular carcinomas. Here we provide evidence that down-regulation of the
...CDK10
gene is mediated by promoter hypermethylation in primary human nasopharyngeal carcinomas (NPC) and NPC-derived cell lines.
Methods
RT-PCR, Western blotting, methylation-specific PCR and bisulfite sequencing were performed to assess the expression and methylation status of the
CDK10
gene in primary NPC samples, NPC-derived cell lines and patient-derived peripheral blood samples. The NPC-derived cell line CNE-2 was selected for treatment with a methylation inhibitor to restore
CDK10
expression. In addition, cell proliferation, invasion and colony formation assays were performed to assess the inhibitory effects of ectopic
CDK10
expression in CNE-2 cells.
Results
Down-regulation of
CDK10
expression in primary NPC samples (23/40, 57.5 %) was found to be significantly correlated with the methylation status of its promoter CpG island (21/40, 52.5 %). Demethylation by 5-aza-dC treatment led to reactivation of the
CDK10
gene in the CNE-2 cell line. Additionally, exogenous expression of
CDK10
in CNE-2 cells strongly suppressed its growth, invasion and colony formation capacities. The high sensitivity (15/40, 37.5 %) and specificity (0 % false positives) of detecting
CDK10
promoter hypermethylation in NPC patient-derived peripheral blood samples suggest that it could be employed as an epigenetic marker for noninvasive cancer diagnosis and recurrence screening.
Conclusion
Our findings implicate that aberrant methylation of the
CDK10
gene promoter occurs frequently in NPC, and that reactivation of
CDK10
might be utilized as a novel epigenetic strategy for the treatment of NPC patients.
Overexpression of TNF-α in the body is critically involved in many diseases. A strategy to construct TNF-α autovaccine by introducing a T cell helper epitope to the protein has been developed and may ...be an alternative because it is cheaper and highly efficient. However, the induction of high level anti-TNF-α neutralizing autoantibodies by TNF-α autovaccine is depend on a proper T cell help epitope. In order to evaluate the effect of different T helper cell epitopes on the immunogenicity of mouse TNF-α (mTNF-α), three T helper cell epitopes, TT (QYIKANSKFIGITEL), HEL (NTDGSTDYGILQINSR), and PADRE (AKFVAAWTLKA), were chosen for this study. The sequence (amino acids 126–140) of mTNF-α was replaced with those of the T cell help epitopes, respectively. The three fusion proteins (mTNF-TT, mTNF-HEL, mTNF-PADRE) were expressed in
Escherichia coli and purified with a simple strategy. The abilities of the proteins elicited TNF-α autoantibodies in BALB/c mice were investigated. The results showed that mTNF-PADRE is the most effective among the three modified TNF-α molecules. In the absence of adjuvant, the therapeutic effect of TNF-PADRE on LPS induced endotoxic shock mice and mTNF-α induced cachexia mice was observed. This study suggests that mTNF-PADRE may be a better candidate of mTNF-α autovaccine.
This special issue introduces the 2017 Social Networks and Social Resources module of the International Social Survey Program (ISSP). This module has been newly developed based on specific, ...up-to-date theoretical and methodological foundations. Within certain limits the designers of this module aimed at allowing comparisons with the previously fielded ISSP modules on Social Networks from 1986 and 2001. The module encompasses measures on social capital and social resources, assessed by both a position generator and questions on social resources coming from network members or formal organizations. They are complemented by other important social network dimensions capturing network structure and opportunities to access and mobilize social relationships. A strength of the new module is to assess multiple dimensions of social networks and social resources, which are crucial either for instrumental or expressive outcomes also introduced in the survey. The special issue includes first an introduction presenting the motivations behind the 2017 new module on Social Networks and Social Resources, the underlying model of the final questionnaire, a description focusing on the core of the social networks and resources measurement with some descriptive results on social capital, network support and sociability, and open the discussion toward some research questions it allows to examine in a comparative perspective.
One of the most important outcomes of market reforms in China has been the emergence of a significant domestic private sector. This book presents an analysis of the management and operation of these ...domestic private firms, which are defined as companies or organizations created by PRC citizens, including township enterprises and collectives.
PDF
