Concurrent cisplatin or cetuximab with radiotherapy in patients with locally advanced head and neck squamous cell carcinoma: A meta-analysis.

BACKGROUND: Concurrent cisplatin with radiotherapy (CRT) or concurrent cetuximab with radiotherapy (BRT) improves outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) compared with radiotherapy alone. Nevertheless, a detailed comparison between CRT and BRT in locally advanced HNSCC is required due to inconclusive results. METHODS: A comprehensive literature search was conducted on PubMed, Web of Science, Cochrane databases, and EMBASE. Studies that evaluated CRT vs BRT in locally advanced HNSCC were included. The primary outcome that was overall survival (OS), whereas the secondary outcomes were progression-free survival (PFS), locoregional control (LRC), and distant metastasis-free survival (DMFS). Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to evaluate prognosis. All the analyses were performed using Stata Statistical Software 12.0. RESULTS: Twenty-three studies, with a total of 8701 patients, were considered eligible and included in this meta-analysis. Our results revealed that patients treated with CRT had longer OS (HR = 0.51, 95%CI, 0.41-0.64, P < .001), PFS (HR = 0.37, 95%CI, 0.23-0.60, P < .001), LRC (HR = 0.46, 95%CI, 0.37-0.57, P < .001), and DMFS (HR = 0.56, 95%CI, 0.40-0.77, P < .001) than those treated with BRT. Furthermore, the results of the subgroup analyses were consistent with the primary analysis. CONCLUSIONS: CRT has a better OS, PFS, LRC, and DMFS than BRT in locally advanced HNSCC, and should be the preferred treatment for patients with the disease.

Identification of BTG1 Status in Solid Cancer for Future Researches Using a System Review and Meta-analysis.

Abundant studies have been conducted to identify how B-cell translocation gene 1 protein (BTG1) gene affects the differentiation, proliferation, metastasis of cancer cells, and how it further regulates the generation or development of diseases to influence the prognosis of patients. However, the data from single research were not powerful enough. The correlations between BTG1 expression and mechanisms of tumorigenesis or prognosis of patients are still in controversial. Our system review and meta-analysis provided a complete explanation about the association between BTG1 expression and clinicopathological features or prognosis of patients, which further laid a foundation for future research on BTG1. Fifteen eligible studies consisting of 1992 participants were included. We uncovered that BTG1 expression in solid tumors was associated with lymph node status (RR=0.66, 95% CI: 0.58-0.75, P=0.142), TMN stage status (RR=2.13, 95% CI: 1.71-2.65, P=0.001), T category (RR=1.90, 95% CI: 1.20-3.00, P=0.000), histological differentiation (RR=1.91, 95% CI: 1.55-2.37, P=0.012), vascular invasion (RR=0.90, 95% CI: 0.57-1.41, P=0.001). BTG1 low expression was significantly associated with overall survival (OS) (HR=0.47, 95% CI: 0.38-0.67, P=0.000). It concluded that BTG1 possessed the potential value for future research and could be recommended as a significant biomarker in solid tumor.

[Determination of selenium in plant samples by hydride generation atomic fluorescence spectrometry].

A method was developed by hydride generation atomic fluorescence spectrometry (HG-AFS)for the determination of selenium in plant samples. Effects of reagent and pre-reduction method on the fluorescence intensity of selenium were studied. The influence of coexisting foreign ions on the determination of selenium was also investigated. Under the optimized digestive and experimental conditions, the linear regression equation was I = 139.98c + 27.71 for Se. The linear range, the correlation coefficient,and the detection limit of Se was 0-10 ng x mL(-1), 1.0000, and 1.45 ng x g(-1) respectively. The recovery of Se (98.9%-101%, mean=100%) was determined through the use of standard reference material. The relative standard deviation for nine replicate analyses was 0.73% for Se content in shrub leaves. This method was verified by analyzing the national reference material (GSV-1)and the found value was in good agreement with the certified value. The proposed method that was successfully used for the determination of Se in plant samples has the advantages of simple operation, low cost, and high efficiency.

1,3-Bis(2-nitro-phen-oxy)propan-2-ol.

In the title compound, C(15)H(14)N(2)O(7), the planes of the two benzene rings form a dihedral angle of 33.16 (17)°. In the crystal, inter-molecular hydrogen bonds involveing the OH group and nitro O atoms link the mol-ecules into chains propagating along the a axis.

[Treatment of great hematoma in brain hemorrhage with multi-point puncture and continuous irrigation-draining].

OBJECTIVE: To investigate the clinical effect of multi-point aspiration combined with continuous irrigation with urokinase in treating great hematoma as the result of brain hemorrhage due to hypertension. METHODS: Ninety-four patients with great hematoma as the result of brain hemorrhage due to hypertension, aged 70, were randomly divided into 2 equal groups: one point puncture group and multi-point puncture group. Both groups underwent puncture under local or general anesthesia and were irrigated with urokinase continually. The outcomes were recorded and analyzed. RESULTS: The case-fatality rate of the multi-point puncture group was 10.87, significantly lower than that of the one-point puncture group (20.83, P < 0.05). The superiority rate of recovery of the multi-point group was 78.26%, significantly higher than that of the one-point puncture group (64.58%, P < 0.05). In 15 days, the resolution rate of brain hematoma of the multi-point group was 67.43%, significantly higher than that of the one point puncture group (23.68%, P < 0.01). The re-hemorrhage rate of the multi-point puncture group was 8.95%, significantly lower than that of the one-point puncture group (12.5%, P < 0.05). CONCLUSION: Multi-point puncture and continuous irrigation decrease the intracranial pressure quickly and suck the hematoma more effectively, especially for the great and irregular hematoma of brain. Continuous urokinase irrigation-drainage is able to keep the concentration of urokinase at an effective level, thus continuously washing, liquefying, draining, and resolving the brain hematoma.

Tumor cell-selective regulation of NOXA by c-MYC in response to proteasome inhibition.

The proteasome controls a plethora of survival factors in all mammalian cells analyzed to date. Therefore, it is puzzling that proteasome inhibitors such as bortezomib can display a preferential toxicity toward malignant cells. In fact, proteasome inhibitors have the salient feature of promoting a dramatic induction of the proapoptotic protein NOXA in a tumor cell-restricted manner. However, the molecular determinants that control this specific regulation of NOXA are unknown. Here, we show that the induction of NOXA by bortezomib is directly dependent on the oncogene c-MYC. This requirement for c-MYC was found in a variety of tumor cell types, in marked contrast with dispensable roles of p53, HIF-1alpha, and E2F-1 (classical proteasomal targets that can regulate NOXA mRNA under stress). Conserved MYC-binding sites identified at the NOXA promoter were validated by ChIP and reporter assays. Down-regulation of the endogenous levels of c-MYC abrogated the induction of NOXA in proteasome-defective tumor cells. Conversely, forced expression of c-MYC enabled normal cells to accumulate NOXA and subsequently activate cell death programs in response to proteasome blockage. c-MYC is itself a proteasomal target whose levels or function are invariably up-regulated during tumor progression. Our data provide an unexpected function of c-MYC in the control of the apoptotic machinery, and reveal a long sought-after oncogenic event conferring sensitivity to proteasome inhibition.

Chemical blockage of the proteasome inhibitory function of bortezomib: impact on tumor cell death.

The proteasome inhibitor bortezomib is emerging as a potent anti-cancer agent. Still, recent clinical trials have revealed a significant secondary toxicity of bortezomib. Consequently, there is much interest in dissecting the mechanism of action of this compound to rationally improve its therapeutic index. The cytotoxic effect of bortezomib is frequently characterized by interfering with downstream events derived from the accumulation of proteasomal targets. Here we identify the first chemical agent able to act upstream of the proteasome to prevent cell killing by bortezomib. Specifically, we show that the polyhydroxyl compound Tiron can function as a competitive inhibitor of bortezomib. This effect of Tiron was surprising, since it is a classical radical spin trap and was expected to scavenge reactive oxygen species produced as a consequence of bortezomib action. The inhibitory effect of Tiron against bortezomib was selective, since it was not shared by other antioxidants, such as vitamin E, MnTBAP, L-N-acetyl-cysteine, and FK-506. Comparative analyses with nonboronated proteasome inhibitors (i.e. MG132) revealed a specificity of Tiron for bortezomib. We exploited this novel feature of Tiron to define the "point of no return" of proteasome inhibition in melanoma cells and to block cell death in a three-dimensional model of human skin. Cells from T-cell lymphoma, breast carcinoma, and non-small cell lung cancer were also responsive to Tiron, suggesting a broad impact of this agent as a bortezomib blocker. These results may have important implications for the analysis of bortezomib in vivo and for the design of drug mixtures containing proteasome inhibitors.

[Follow-up study on psychic and neuropathic delayed effects of acute organophosphorus pesticides poisoning].

OBJECTIVE: To study the delayed effect on neuropsychopathy and its related factors after acute organophosphorus pesticides poisoning (AOPP). METHODS: Two hundred and fifty-seven cases of AOPP in the observation period were chosen to follow-up 2 months later from the 4 county hospitals in Shandong Province where the incidence of organophosphorus pesticide poisoning is high. RESULTS: Nine cases of organophosphate induced delayed polyneuropathy (OPIDP) were found and the incidence rate was 3.5%. The occurrence of OPIDP were related to the need for emergent artificial respiration, and the degree of poisoning, and the kinds of organophosphorus pesticides (Ops). The positive rate of symptoms of peripheral nerves, central nerves and psychogeny except auditory and visual hallucination after poisoning was significantly higher than that before (P < 0.05). The patient's situation of health, economy and work became statistically worse (P < 0.05). CONCLUSION: We found some had delayed effects on neuropsychopathy after AOPP which could debase the patient's life quality. The control measure should be administered as early as possible.

Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes.

An ideal therapeutic for cancer would be one that selectively targets to tumor cells, is nontoxic to normal cells, and that could be systemically delivered, thereby reaching metastases as well as primary tumor. Immunoliposomes directed by monoclonal antibody or its fragments are promising vehicles for tumor-targeted drug delivery. However, there is currently very limited data on gene delivery using these vehicles. We have recently described a cationic immunoliposome system directed by a lipid-tagged, single-chain antibody Fv fragment (scFv) against the human transferrin receptor (TfR) that shows promising efficacy for systemic p53 tumor suppressor gene therapy in a human breast cancer metastasis model. However, the extremely low yield of this lipid-tagged scFv limited further downstream development and studies. Here we report a different expression strategy for the anti-TfR scFv, which produces high levels of protein without any tags, and a different approach for complexing the targeting scFv to the liposomes. This approach entails covalently conjugating the scFv to the liposome via a cysteine at the 3'-end of the protein and a maleimide group on the liposome. Our results show that this conjugation does not impair the immunological activity or targeting ability of the scFv. The scFv-cys targets the cationic liposome-DNA complex (lipoplex) to tumor cells and enhances the transfection efficiencies both in vitro and in vivo in a variety of human tumor models. This scFv-immunoliposome can deliver the complexed gene systemically to tumors in vivo, where it is efficiently expressed. In comparison with the whole antibody or transferrin molecule itself, the scFv has a much smaller size for better penetration into solid tumors. It is also a recombinant protein rather than a blood product; thus, large scale production and strict quality control are feasible. This new approach provides a promising system for tumor-targeted gene delivery that may have potential for systemic gene therapy of various human cancers.

Self-assembly of a virus-mimicking nanostructure system for efficient tumor-targeted gene delivery.

Molecular therapy, including gene therapy, is a promising strategy for the treatment of human disease. However, delivery of molecular therapeutics efficiently and specifically to the target tissue remains a significant challenge. A human transferrin (Tf)-targeted cationic liposome-DNA complex, Tf-lipoplex, has shown high gene transfer efficiency and efficacy with human head and neck cancer in vitro and in vivo (Xu, L., Pirollo, K.F., Tang, W.H., Rait, A., and Chang, E.H. Hum. Gene Ther. 1999;10:2941-2952). Here we explore the structure, size, formation process, and structure-function relationships of Tf-lipoplex. We have observed Tf-lipoplex to have a highly compact structure, with a relatively uniform size of 50-90 nm. This nanostructure is novel in that it resembles a virus particle with a dense core enveloped by a membrane coated with Tf molecules spiking the surface. More importantly, compared with unliganded lipoplex, Tf-lipoplex shows enhanced stability, improved in vivo gene transfer efficiency, and long-term efficacy for systemic p53 gene therapy of human prostate cancer when used in combination with conventional radiotherapy. On the basis of our observations, we propose a multistep self-assembly process and Tf-facilitated DNA cocondensation model that may provide an explanation for the resultant small size and effectiveness of our nanostructural Tf-lipoplex system.