肺结核化疗后出现胃肠道反应的护理

目的:通过对肺结核化疗后出现胃肠道反应的护理,以达到提高肺结核化疗的疗效和防止并发症的目的。方法:为肺结核化疗后出现胃肠道反应的患者提供科学的护理。结果:本组47例患者经治疗护理后,32例仅有胃肠道症状的患者,基本完成在医院的治疗。15例有肝功能损害的患者,除2例自行出院外,其余均在保肝、降酶治疗的基础上完成疗程。结论:有效的护理措施可以减轻抗结核药引起的胃肠道反应。

Nuclear factor kappa B: A marker of chemotherapy for human stage Ⅳ gastric carcinoma

AIM： To detect the nuclear factor kappa B （NF-κB） condition in human stage IV gastric carcinoma patients and to explore the correlation between NF-κB activation and survival of these patients after chemotherapy. METHODS： Expression of NF-κB-p65 was determined by immunohistochemical analysis. Activity of NF-κB DNA-binding in carcinoma tissue was detected by electrophoretic mobility shift assay. Kaplan-Meier survival analysis was performed to show the relation between NF-κB and progression-free survival （PFS） or overall survival （OS） of the patients. RESULTS： The positive expression rate of NF-κB-p65 in 60 gastric cancer tissue samples was 76.7% （46160）. The expression of NF-κB-p65 was reduced in adjacent carcinoma and normal tissue samples. Electrophoretic mobility shift assay （EMSA） analysis showed a strong activation of NF-κB in cancer tissue samples. A survival difference was found in NF-κB-p65 positive and negative patients. NF-κB-p65 expression was negative in cancer tissue samples （n = 14）. PFS was 191.40 ± 59.88 d and 152.93 ±16.99 d, respectively, in patients with positive NF-κB-p65 expression （n = 46） （P = 0.4028）. The survival time of patients with negative and positive NF-κB-p65 expression was 425.16 ±61.61 d and 418.85 ±42.98 d, respectively （P = 0.7303）. Kaplan-Meier analysis showed no significant difference in PFS or OS. The 46 patient tissue which positive NF-κB-p65 expression was found in the tissue samples from the 46 patients whose PFS and OS were 564.89 ± 75.94 d and s 352.37 ±41.32 d, respectively （P = 0.0165）. CONCLUSION： NF-κB is activated in gastric carcinoma tissue, which is related to the OS after chemotherapy.

The predictive value of vascular endothelial growth factor and Ki-67 expression on neoadjuvant therapy in rectal cancer

Objective： To investigate the expressions of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （Ki-67） in patients with rectal adenocarcinoma and their associations with neoadjuvant therapy. Methods： The expressions of Ki-67 and VEGF in 32 cases of rectal adenocarcinoma, including both pretreatment tumor biopsies and postoperative specimen, were detected by immunohistochemistry using specific antibodies, and were correlated with clinicopathological factors. Results： The intensity of VEGF staining was significantly correlated with lymph nodal metastasis （P =0.033）, depth of tumor invasion （P =0.007） and tumor stage （P= 0.016）, but not with histological types, tumor sizes, patients＇ ages and genders （P 〉 0.05）. Low level of VEGF expression had significant correlation with the high sensitivity of response to neoadjuvant therapy （P = 0.016）. The transient increase of VEGF expression could be seen after neoadjuvant therapy （P = 0.035）. Ki-67 labeling index （Ki-67-LI） was significantly correlated with lymph node metastasis （P = 0.028）, but not correlated to tumor sizes, patients＇ ages and genders （P 〉 0.05）. Tumors with lower Ki-67-LI were more sensitive to neoadjuvant therapy （P = 0.032）. The Ki-67 level decreased after neoadjuvant therapy, but no statistical significance was found （P 〉 0.05）. Conclusion： Our results demonstrate that the expression of VEGF and Ki-67 in pretreatment rectal adenocarcinoma biopsies may be predictive of tumor response to neoadjuvant therapy.

Phosphorylated KDR can be located in the nucleus of neoplastic cells

KDR （kinase insert domain receptor） phosphorylation induces several effects which lead eventually to cell proliferation and survival. The precise mechanisms by which KDR, once it is activated, communicates with the nucleus are starting to be understood but have not yet been completely unravelled. Two in vitro studies on animal cell lines reported in the literature have demonstrated that, following stimulation with VEGF, KDR is actually translocated within the nucleus. Our aim was to investigate whether this translocation occurs in human cells both in vitro and in vivo. Using laser scanning confocal microscopy, a variable nuclear localization of phosphorylated and total KDR in cell lines and tumour samples was found. In human neoplastic cell lines, hypoxic stimulation greatly increased the nuclear amount of total KDR but less so that of the phosphorylated form. Only after hypoxia and VEGF stimulation there was a comparably increased expression of phosphorylated and total KDR observed in the nuclei of these cells. We conclude that neoplastic cells show a variable expression of total and phosphorylated KDR in the nucleus. The precise functional meaning of nuclear location remains to be established.

Hepatic preconditioning of doxorubicin in stop-flow chemotherapy:NF-κB/IκB-α pathway and expression of HSP72

AIM:To provide hepatic protection through administration of doxorubicin before stop-flow chemotherapy (SFC) and to investigate the expression of heat shock protein 72 (HSP72) and role of nuclear factor kappa B (NF-κB) in this effect. METHODS: The hepatic preconditioning of doxorubicin was established in a porcine model by injection of doxorubicin (1 mg/kg) before SFC. The experimental animals were randomized into two groups: groups receiving doxorubicin (DOX) and normal saline (NS). Serial serum and tissue samples were taken from both groups to evaluate the protection of doxorubicin. Western blot and immunoprecipitation were applied to detect the expression of HSP72, NF-κB p65 protein, inhibitor κB-α (IκB-α) and phosphorylated IκB-α as well. The expression of tumor necrosis factor α (TNF-α) was estimated by semiquantitative RT-PCR. And the extent of the hepatic injury was estimated with the level of serum aminotransferases. RESULTS: An abundance production of HSP72 in porcine liver was observed after 24 h of intravenous administration of doxorubicin, but without any change in the expression of NF-κB p65 subunit in cytoplasm. NF-κB p65 subunit accumulated in nuclei at the end of SFC and reached its highest level at 30 min after the restoration of the abdominal circulation and decreased gradually during the 6 h after SFC in NS group, while there was little change in DOX group. There was also a slight decrease of IκB-α at 30 min after the restoration of the abdominal circulation in NS group accompanying with the appearance of phosphorylated IκB-α. The expression of TNF-α was significantly higher in NS group than that in DOX group (average 1.40±0.17 vs 0.62±0.22, P<0.01) at serial time points after SFC. Serum ALT and AST levels of NS group were higher after 24 h than those of DOX group (93.2±7.8 IU/L vs 53.3±13.9 IU/L, 217.0±29.4 IU/L vs 155.0±15.6 IU/L for ALT and AST respectively, P<0.05) and after 48 h than those of DOX group (66.6±18.1 IU/L vs 43.3±16.7 IU/L, 174.4±21.3 IU/L vs 125.7±10.5 IU/L for ALT and AST respectively, P<0.05). CONCLUSION: Doxorubicin renders the liver to be tolerant to the hepatic influence in SFC in a porcine model through the NF-κB/IκB-αpathway with the expression of HSP72.

Expression and significance of microRNA-32 in multiple myeloma

Objective: This study was aimed to explore the expression of microRNA-32(miR-32) in multiple myeloma(MM), and study its association with β2-microglobulin and staging of MM by Durie-Salmon classification. Methods: The expression level of miR-32 in bone marrow mono-nuclear cells of MM were examined by real-time polymerase chain reaction(real-time PCR), and the correlations between the expression level of miR-32 and related clinic pathologic features β2-microglobulin, staging of MM by Durie-Salmon classification were further analyzed. Results: The expression of miR-32 in MM patients was obviously higher than that in normal control(P < 0.05). The expression of miR-32 in relapsed/ refractory MM patients was obviously higher than that in newly diagnosed MM patients. The expression of miR-32 in MM patients decreased after chemical therapy than that before treatment, especially in effective group(P < 0.05). There was no statistically significant change in ineffective/progress group after chemical therapy(P > 0.05).The expression of miR-32 was associated to staging of MM and β2-microglobulin level. Conclusion: Expression level of miR-32 in MM patients is significantly higher than that in normal bone marrow, these data indicated that miR-32 may play an important role in the development of MM. High-regulated expression of miR-32 was associated with β2-microglobulin and staging of MM by Durie-Salmon classification.

Clinical study on radiofrequency combined with ^(131)I therapy for dedifferentiated thyroid carcinomas

Objective:The aim of this study was to explore clinical efficiency of radio frequency combined with 131I therapy for dedifferentiated thyroid carcinoma.Methods:All patients have been treated by radiofrequency connected with 131I in 29 cases of dedifferentiated thyroid carcinoma which performed radionuclide imaging and Ig array of blood serum before and after therapy,respectively.Results:There were 4(4/29) positive cases of radionuclide imaging before treatment and 19(19/29) cases 2 weeks after therapy,25(25/29) cases of overall efficacy and 15(15/29) curative cases. Conclusion: Radiofrequency connected with 131I improve clinical efficacy of 131I treatment for dedifferentiated thyroid cancer of thyroid in view of higher absorbing 131I of thyroid cancerous cell.

Chemical and structural biology of nucleic acids and protein-nucleic acid complexes for novel drug discovery

Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic agents.Targeting nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the main reasons.Fortunately,many important structures of nucleic acids and their protein complexes have been determined over the past decade,which provide novel platforms for future drug design and discovery.In this review,we describe some useful nucleic acid structures,particularly their interactions with the ligands and therapeutic candidates or even drugs.We summarize important information for designing novel potent drugs and for targeting nucleic acids and protein-nucleic acid complexes to treat cancers and overcome the drug-resistant problems.

Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles

Magnetic nanopartides have been used as drug delivery vehicles against a number of cancer cells. Most of these theranostic formulations have used solid iron oxide nanoparticles （SIONPs） loaded with chemotherapeutics as nano-carrier formulation for both magnetic resonance imaging （MRI） and cancer therapy. In this study, we applied the dopamine-plus-human serum albumin （HSA） method to modify hollow iron oxide nanoparticles （HIONPs） and encapsuated doxorubicin （DOX） within the hollow porous structure of the nano-carrier. The new delivery system can load more drug than solid iron oxide nanoparticles of the same core size using the same coating strategy. The HIONPs-DOX formulation also has a pH-dependent drug release behaviour. Compared with free DOX, the HIONPs-DOX were more effectively uptaken by the multidrug resistant OVCAR8- ADR cells and consequently more potent in killing drug resistant cancer cells. MRI phantom and cell studies also showed that the HIONPs-DOX can decrease the T2 MRI signal intensity and can be used as a MR/contrast agent while acting as a drug delivery vehicle. For the first time, the dual application of chemo drug transport and MR imaging using the HIONPs-DOX formulation was achieved against both DOX-sensitive and DOX-resistant cancer cells.