Tengzhou Central Peoples Hospital
Tengzhou Central Peoples Hospital
Zhang K.,Tengzhou Central Peoples Hospital |
Yuan Q.,Tengzhou Central Peoples Hospital
Journal of Cancer Research and Therapeutics | Year: 2016
Lung cancer continues to be a major health problem and the most common cancer-related mortality worldwide with about 80%-85% patients suffering from nonsmall cell lung cancer (NSCLC). More than 80% of NSCLC cases are often diagnosed as advanced stage and harbor epidermal growth factor receptor (EGFR) activating mutation. Although great success in initial response to EGFR-Tyrosine kinase inhibitors (EGFR-TKIs) are found in EGFR-mutant NSCLC patients, acquired resistance usually occurs on the continuous treatment. Here, we provide an overview on the mechanism of acquired resistance to EGFR-TKIs in NSCLC therapy as well as current preclinical and clinical evidence of new therapy strategies and inhibitors in the treatment of NSCLC. Many studies have shown that original or induced T790M mutation, human EGFR 2 amplification, and activated secondary signaling such as MET amplification or phosphatidylinositol 3-kinase mutation can lead to acquired resistance to EGFR-TKIs. In addition, transformation from NSCLC to SCLC or conferred epithelial to mesenchymal transition has also been identified as mechanisms of acquired resistance to EGFR-TKIs. Increasing evidence has proven that non-coding RNA including long noncoding RNAs and microRNAs or new EGFR mutation is involved in acquired resistance. Preclinical and clinical Phase 1-3 evidence on combination drug therapy or new generation inhibitors with different tumor-Targeting approaches have made those strategies the promising options for EGFR-TKI-resistant NSCLC therapy. This review aims to get deep insight into providing a state-of-The-Art overview of the recent advances in the mechanisms of acquired resistance and new strategies for targeted cancer therapy in EGFR-TKI-resistant NSCLC.
Cui G.,Xuzhou Medical College |
Ye X.,Xuzhou Medical College |
Zuo T.,Soochow University of China |
Zhao H.,Xuzhou Central Hospital |
And 4 more authors.
Neuroscience Letters | Year: 2013
Toll-like receptors (TLRs) mediated signaling is mainly implicated in inflammatory activation which contributes to the initiation and progression of stroke. Using a model of transient global cerebral ischemia (tGCI) in rats, we investigated the changes of pro-inflammation mediators and tested the effects of Chloroquine pretreatment on the expression of pro-inflammation mediators after stroke. Adult Male Sprague-Dawley (SD) rats were subjected to transient global cerebral ischemia (tGCI) and treated without or with Chiloquin pretreatment (60. mg/kg) 2. h before tGCI. Short-term spatial memory capacity, Western blot assay and semi-quantitive RT-PCR were performed. Compared to sham operated rats, tGCI rats showed worsened learning and memory capacity and increased expression of TLR3, interferon regulatory factor 3 (IRF3), and interferon β (IFN-β) in the Hippocampus after stroke. Chloroquine pretreatment significantly enhanced rats' short-term spatial memory capacity and attenuated the expression of TLR3, IFR3, and IFN-β in the Hippocampus compared to non-treatment control in tGCI rats. Therefore, Chloroquine pretreatment of stroke inhibits inflammatory response and improves short-term spatial memory capacity. The TLR3/IFR3-IFN-β signaling pathway may contribute to the reduced inflammatory response after stroke. Chloroquine warrants further investigation as a therapeutic agent for the treatment of stroke. © 2013 Elsevier Ireland Ltd.
Yang J.,Affiliated Hospital of Shandong Medical College |
Yang K.-Q.,Affiliated Hospital of Shandong Medical College |
Qiu L.,Tengzhou Central Peoples Hospital
Environmental Toxicology and Pharmacology | Year: 2017
The green synthesis of tin oxide nanoparticles (SnO2 NPs) using vitamin C (Vc) as a reducing agent via a biosynthetic approach is described. The effect of Vc-stabilized SnO2 NPs on the body weight of neonatal rats is also studied. The prepared SnO2NPs were characterized using spectroscopic and microscopic instrumental techniques including transmission electron microscopy (TEM), UV–visible spectrophotometry (UV–vis), X-ray diffraction and Fourier transform infrared spectroscopy, which confirmed the formation of NPs. TEM images confirmed the formation of spherical NPs with a mean particle size of around 30 nm. The body weight studies showed that vitamin-C stabilized SnO2 NPs promote a higher body weight gain compared to raw SnO2 NPs. It was also shown that Vc can counteract the decreased body weight caused by SnO2 NPs in neonatal rats. © 2017 Elsevier B.V.
Liu X.-Y.,Tengzhou Central Peoples Hospital |
Zhang J.-Y.,Peking University
Vision Research | Year: 2016
Dichoptic training is a recent focus of research on perceptual learning in adults with amblyopia, but whether and how dichoptic training is superior to traditional monocular training is unclear. Here we investigated whether dichoptic training could further boost visual acuity and stereoacuity in monocularly well-trained adult amblyopic participants. During dichoptic training the participants used the amblyopic eye to practice a contrast discrimination task, while a band-filtered noise masker was simultaneously presented in the non-amblyopic fellow eye. Dichoptic learning was indexed by the increase of maximal tolerable noise contrast for successful contrast discrimination in the amblyopic eye. The results showed that practice tripled maximal tolerable noise contrast in 13 monocularly well-trained amblyopic participants. Moreover, the training further improved stereoacuity by 27% beyond the 55% gain from previous monocular training, but unchanged visual acuity of the amblyopic eyes. Therefore our dichoptic training method may produce extra gains of stereoacuity, but not visual acuity, in adults with amblyopia after monocular training. © 2017 Elsevier Ltd.
Liu X.-Y.,Capital Medical University |
Liu X.-Y.,Tengzhou Central Peoples Hospital |
Zhang T.,Beijing Normal University |
Jia Y.-L.,Zaozhuang Municipal Hospital |
And 2 more authors.
Investigative Ophthalmology and Visual Science | Year: 2011
PURPOSE. To investigate the therapeutic impact of perceptual learning on juvenile amblyopia that is no longer responsive to patching treatment (PT group) or was never patch treated (NPT group). METHODS. Ten PT and 13 NPT subjects aged 8 to 17 years were trained with a grating acuity task for 40 to 60 sessions. Half in each group were further trained with single or crowded tumbling E acuity tasks for 8 to 10 sessions. RESULTS. Training improved grating acuity by -2.1% in the PT eyes and 36.1% in the NPT eyes, along with a boost of single and crowded E acuities by 0.9 or 0.7 lines in the PT eyes and 1.5 and 1.2 lines in the NPT eyes, in contrast to a nearly 5-line improvement in the same PT eyes after previous patching treatment. Stereoacuity was improved in some PT and NPT eyes. The single and crowded E acuity improvements were not significantly dependent on the pretraining acuity. The single and crowded E acuity and stereoacuity improvements were uncorrelated with grating acuity improvement, suggesting some random training impacts on different tasks and individuals. Further direct single and crowded E acuity training generated an additional 0.2- and 0.2-line boost for PT eyes and a 0.4- and 0.5-line boost for NPT eyes, resulting in overall single and crowded E acuity gains of 1.4 and 1.0 lines for PT eyes and 2.2 and 1.8 lines for NPT eyes. CONCLUSIONS. Perceptual learning has a small but significant therapeutic impact on both PT and NPT juvenile eyes, which is most likely to have clinical values for eyes with mild amblyopia. Early diagnosis and treatment are most important and effective. © 2011 The Association for Research in Vision and Ophthalmology, Inc.
Zhang K.,Tengzhou Central Peoples Hospital
Journal of Burn Care and Research | Year: 2017
The objective of this study was to develop rat model of second-degree burn pain and test analgesic efficacy of local thiamine administration. Automatic temperature-controlled hot plate was set at 85 ± 0.1°C with a filter paper on the top. Rats were thrust on hot plate landing on plantar surface for 4 to 7 and 10 seconds, respectively. Burnt skin was observed. Hematoxylin and eosin staining and Masson staining were used to monitor burn degree. Gait analysis detected change of locomotion. Allodynia and hyperalgesia in the burnt area were evaluated with von Frey test and Hargreaves Test, and ongoing pain was detected with conditional place preference test. Markers for the activity of microglia (Iba1), astrocytes (GFAP), and neurons (c-fos) were detected with immunofluorescence. Finally, thiamine was injected into blisters to observe its effect on burn pain. Blisters on burnt skin, space between dermal and epidermal layers in hematoxylin and eosin staining and burn injury limiting in dermal layer in Masson stain all indicated that burn injury lasting for 7 seconds matched second-degree burn. Behavioral tests revealed allodynia, ongoing pain, and increased expression of c-fos, GFAP, and Iba1, as well as the absence of hyperalgesia in Burn7s. Burn injury reduced distance of second and fourth digits. MK801 could relieve allodynia in Burn7s. Local administration of 1, 2, and 4 mg of thiamine had no effect on the allodynia, but 2 and 4 mg of thiamine also could induce CCP in Burn7s. A rat model of second-degree burn pain was developed and local administration of thiamine provided relief from pain. © 2017 The American Burn Association
Fu M.,Linyi Peoples Hospital |
Shi W.,Linyi Tumor Hospital |
Li Z.,Tengzhou Central Peoples Hospital |
Liu H.,Linyi Peoples Hospital
Biochemical and Biophysical Research Communications | Year: 2016
Over-expression and aberrant activation of histone deacetylases (HDACs) are often associated with poor prognosis of hepatocellular carcinoma (HCC). Here, we evaluated the potential anti-hepatocellular carcinoma (HCC) cell activity by resminostat, a novel pan HDAC inhibitor (HDACi). We demonstrated that resminostat induced potent cytotoxic and anti-proliferative activity against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, resminostat treatment in HCC cells activated mitochondrial permeability transition pore (mPTP)-dependent apoptosis pathway, which was evidenced by physical association of cyclophilin-D and adenine nucleotide translocator 1 (ANT-1), mitochondrial depolarization, cytochrome C release and caspase-9 activation. Intriguingly, the mPTP blockers (sanglifehrin A and cyclosporine A), shRNA knockdown of cyclophilin-D or the caspase-9 inhibitor dramatically attenuated resminostat-induced HCC cell apoptosis and cytotoxicity. Reversely, HCC cells with exogenous cyclophilin-D over-expression were hyper-sensitive to resminostat. Intriguingly, a low concentration of resminostat remarkably potentiated sorafenib-induced mitochondrial apoptosis pathway activation, leading to a profound cytotoxicity in HCC cells. The results of this preclinical study indicate that resminostat (or plus sorafenib) could be further investigated as a valuable anti-HCC strategy. © 2016 Elsevier Inc.
Lv Y.-L.,Southern Medical University |
Yuan D.-M.,Nanjing University |
Wang K.,Guangxi Medical University |
Miao X.-H.,Nanjing University |
And 4 more authors.
Journal of Thoracic Oncology | Year: 2011
Accurate clinical staging of mediastinal lymph nodes (MLNs) of patients with non-small cell lung cancer (NSCLC) is important in determining therapeutic options and prognoses. Integrated positron emission tomography and computed tomography (PET/CT) scanning is becoming widely used for MLN staging in patients with NSCLC. We performed a bivariate meta-analysis to determine the pooled sensitivity (SEN) and specificity (SPE) of this imaging modality. Methods: The PubMed/MEDLINE, Embase, and SpringerLink databases were searched for articles related to PET/CT for MLN staging in patients with NSCLC. SEN and SPE were calculated for every study. Hierarchical summary receiver operating characteristic curves were used to summarize overall test performance and assess study quality. Potential between-study heterogeneity was explored by subgroup analyses. Results: Fourteen of 330 initially identified reports were included in the meta-analysis. When we did not consider the unit of analysis, the pooled weighted SEN and SPE were 0.73 (95% confidence interval [CI]: 0.65-0.79) and 0.92 (95% CI: 0.88-0.94), respectively. In the patient-based data analysis, the pooled weighted SEN was 0.76 (95% CI: 0.65-0.84) and the pooled weighted SPE was 0.88 (95% CI: 0.82-0.92). In the MLN-based data analysis, the pooled SEN was 0.68 (95% CI: 0.56-0.78) and the pooled SPE was 0.95 (95% CI: 0.91-0.97). Conclusions: Integrated PET/CT is a relatively accurate noninvasive imaging technique, with excellent specificity for MLN staging in patients with NSCLC. Nevertheless, current evidence suggests that we should not depend on the results of PET/CT completely for MLN staging in patients with NSCLC. Copyright © 2011 by the International Association for the Study of Lung Cancer.
Gai Z.,University of Zürich |
Chu L.,Shandong University |
Chu L.,Tengzhou Central Peoples Hospital |
Hiller C.,University of Zürich |
And 5 more authors.
American Journal of Physiology - Renal Physiology | Year: 2014
Although the kidney is believed to play a minor role in bile acid (BA) excretion, chronic renal failure (CRF) has been reported to be associated with increased serum bile acid levels and alterations in BA homeostasis. The mechanisms for elevated BA levels are poorly understood in both clinical and experimental studies. This study was designed to examine the effects of naturally progressing CRF of longer duration on the hepatic and renal mRNA and protein levels of the BA-synthesizing enzyme Cyp7a1 and the BA transporters Ntcp, Bsep, Mrp3, Ost-α, and Ost-β. Sprague-Dawley rats were randomized to the CRF group (5/6 nephrectomy) or to the sham-operated control group and were analyzed 8 wk after surgery. Results obtained in the CRF rats were compared with those obtained in rats that had undergone uninephrectomy (UNX). The CRF group exhibited significantly increased plasma cholesterol and BA concentrations. Hepatic Cyp7a1 mRNA and protein levels were almost identical in the two groups. Hepatic Mrp3, Ost-α, and Ost-β expression was increased, suggesting increased basolateral efflux of bile acids into the blood. However, no such changes in BA transporter expression were observed in the remnant kidney. In UNX rats, similar changes in plasma BA levels and in the expression of BA transporters were found. We hypothesize that the increase in plasma BA is an early event in the progression of CRF and is caused by increased efflux across the basolateral hepatocyte membrane. © 2014 the American Physiological Society.
Wan J.,Fudan University |
Gai Y.,Tengzhou Central Peoples Hospital |
Li G.,Fudan University |
Tao Z.,Fudan University |
Zhang Z.,Fudan University
Clinical Colorectal Cancer | Year: 2015
Background The incidence rates of colorectal cancer (CRC) in young individuals are increasing. There has been a significant improvement in overall survival in CRC because of advances in adjuvant chemotherapy and chemoradiotherapy over the past decades. However, these procedures may compromise the function of the reproductive system, and ovarian failure and premature menopause may occur. The objective of this analysis was to determine the incidence of long-term amenorrhea (≥ 12 months) in women with CRC aged 40 years and younger after adjuvant treatment. Patients and Methods The authors identified 162 premenopausal women with CRC aged 40 years or younger who were treated with adjuvant chemotherapy and chemoradiotherapy at Fudan University Shanghai Cancer Center from January 2008 to December 2012. One hundred twenty-three patients met all eligibility criteria and had sufficient follow-up for evaluation. The median age at diagnosis in patients with colon and rectal cancers was, respectively, 36 and 35 years (range, 17-40 and 24-40 years). Results All patients had regular menses before treatment; 3 patients with colon cancer (4.2%) experienced long-term amenorrhea, and 48 patients with rectal cancer (94.1%) experienced long-term amenorrhea. The incidence of amenorrhea was significantly lower in patients with colon cancer (4.2%; 3 of 72) than in patients with rectal cancer (94.1%; 48 of 51) (P <.01). Conclusion In this retrospective series, the incidence of amenorrhea in patients with colon and rectal cancers was 4.2% and 94.1%, respectively. We believe our data support the fact that young female patients with CRC, especially those with rectal cancer who are scheduled to undergo pelvic irradiation, should be counseled regarding fertility preservation options, including ovarian transposition and cryopreservation of ovarian tissue, embryo, or oocyte. © 2015 Elsevier Inc.