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1.
Int J Oncol ; 65(3)2024 Sep.
Article in English | MEDLINE | ID: mdl-39092544

ABSTRACT

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the GAPDH bands shown for the western blots portrayed in Fig. 2 (associated with the α­SMA proteins) on p. 1482 were strikingly similar to the GAPDH bands associated with the CAF64 and NF64 experiments in Fig. 4 on p. 1485. After re­examining their original data, the authors have realized that the GAPDH protein bands correctly shown in Fig. 4 had inadvertently been included in Fig. 2. The revised version of Fig. 2, showing the GAPDH bands that were correctly associated with the α­SMA proteins, is shown opposite. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree to its publication. Note that this error did not grossly affect either the results or the conclusions reported in this study; furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 45: 1479­1488, 2014; DOI: 10.3892/ijo.2014.2562].

2.
Biomaterials ; 306: 122495, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38309053

ABSTRACT

In managing severe traumatic brain injury (TBI), emergency surgery involving the removal of damaged brain tissue and intracerebral hemorrhage is a priority. Secondary brain injury caused by oxidative stress and energy metabolic disorders, triggered by both primary mechanical brain damage and surgical insult, is also a determining factor in the prognosis of TBI. Unfortunately, the effectiveness of traditional postoperative intravenous neuroprotective agents therapy is often limited by the lack of targeting, timeliness, and side effects when neuroprotective agents systemically delivered. Here, we have developed injectable, intelligent, self-assembling hydrogels (P-RT/2DG) that can achieve precise treatment through intraoperative application to the target area. P-RT/2DG hydrogels were prepared by integrating a reactive oxygen species (ROS)-responsive thioketal linker (RT) into polyethylene glycol. By scavenging ROS and releasing 2-deoxyglucose (2DG) during degradation, these hydrogels functioned both in antioxidation and energy metabolism to inhibit the vicious cycle of post-TBI ROS-lactate which provoked secondary injury. In vitro and in vivo tests confirmed the absence of systemic side effects and the neuroprotective function of P-RT/2DG hydrogels in reducing edema, nerve cell apoptosis, neuroinflammation, and maintaining the blood-brain barrier. Our study thus provides a potential treatment strategy with novel hydrogels in TBI.


Subject(s)
Brain Injuries , Neuroprotective Agents , Humans , Reactive Oxygen Species/metabolism , Neuroprotective Agents/pharmacology , Oxygen/metabolism , Hydrogels/pharmacology , Brain/metabolism , Brain Injuries/drug therapy , Energy Metabolism
3.
Cancer Sci ; 114(3): 1067-1074, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36382603

ABSTRACT

This trial was initiated to evaluate the efficacy and safety of pyrotinib in combination with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent/metastatic colorectal cancer (CRC). In this single-arm, open-label, multicenter, phase 2 trial patients with HER2-positive recurrent/metastatic CRC were enrolled and received oral pyrotinib 400 mg once a day plus intravenous trastuzumab 8 mg/kg loading dose followed by 6 mg/kg once every 3 weeks. The primary endpoint was the objective response rate (ORR). Disease control rate (DCR), progression-free survival (PFS), duration of response, and safety were assessed as secondary endpoints. From December 2019 to October 2021, a total of 20 patients were enrolled and 18 of them were evaluable for response. All patients were B-rapidly accelerated fibrosarcoma (BRAF) wild type. Four patients achieved partial response, with an ORR of 22.2% (4/18, 95% confidence interval [CI] 6.4-47.6) and DCR of 61.1% (11/18, 95% CI 35.8-82.7), while the ORR and DCR were 33.3% (4/12, 95% CI 13.8-60.9) and 83.3% (10/12, 95% CI 51.6-97.9), respectively, in RAS wild-type patients. At the time of cut-off day, median follow-up was 10.7 months (range 3.8-13.8). The median PFS was 3.4 months (95% CI 1.8-4.3) in the overall population and 4.3 months (95% CI 3.2-8.5) in the RAS wild-type group. The most common adverse event of grade ≥3 was diarrhea (13/20, 65.0%). Pyrotinib combined with trastuzumab showed promising antitumor activity and a manageable safety profile in patients with RAS/BRAF wild-type HER2-positive advanced CRC.


Subject(s)
Breast Neoplasms , Colorectal Neoplasms , Humans , Female , Trastuzumab/adverse effects , Proto-Oncogene Proteins B-raf , Neoplasm Recurrence, Local/drug therapy , Receptor, ErbB-2/metabolism , Colorectal Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy
4.
Article in English | MEDLINE | ID: mdl-35833273

ABSTRACT

Traumatic brain injury (TBI) is accompanied by the overload of reactive oxygen species (ROS), which can result in secondary brain injury. Although procyanidins (PCs) have a powerful free radical scavenging capability and have been widely studied in the treatment of TBI, conventional systemic drug therapy cannot make the drug reach the targeted area in the early stage of TBI and will cause systemic side effects because of the presence of the blood-brain barrier (BBB). To address this tissue, we designed and fabricated a ROS-scavenging functional hydrogel loaded PC (GelMA-PPS/PC) to deliver the drug by responding to the traumatic microenvironment. In situ injection of the GelMA-PPS/PC hydrogel effectively avoided the BBB and was directly applied to the surface of brain tissue to target the traumatic area. Hydrophobic poly(propylene sulfide)60 (PPS60), an ROS quencher and H2O2-responsive substance, was covalently bound to GelMA and exposed in response to the trauma microenvironment. At the same time, the H2O2 response of PPS60 further caused the structure of the hydrogel to degrade and release the encapsulated PC. Then PC could regulate the oxidative stress response in the cells and synergistically deplete ROS to play a neurotrophic protective role. This work suggests a novel method for the treatment of secondary brain injury by inhibiting the oxidative stress response after TBI.

5.
PLoS One ; 16(11): e0259570, 2021.
Article in English | MEDLINE | ID: mdl-34739514

ABSTRACT

Inonotus obliquus Polysaccharide (IOP) is a large molecule extracted from Inonotus obliqus, a medicinal fungus, which has a wide range of biological activities and has been shown to be associated with inflammation. The purpose of this study is to investigate whether IOP can help to reduce acute endometritis by regulating intestinal flora. We observed pathological changes in mice with endometritis following treatment with IOP and evaluated changes in the levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α), and further studied the effects of IOP on the intestinal flora of endometritis mice using 16S rRNA high-throughput sequencing. The results showed that IOP improved the condition of uterine tissues and reduced the release of pro-inflammatory cytokines. Meanwhile, the 16S rRNA sequencing results showed that IOP could regulate the changes in intestinal microflora at the level of genera, possibly by changing the relative abundance of some genera.


Subject(s)
Endometritis , Gastrointestinal Microbiome , Acute Disease , Animals , Female , Interleukin-6 , Mice , RNA, Ribosomal, 16S , Uterus
6.
Int J Oncol ; 57(4): 939-955, 2020 10.
Article in English | MEDLINE | ID: mdl-32945394

ABSTRACT

Lung cancer has the highest incidence and mortality rates among the malignant tumor types worldwide. Platinum­based chemotherapy is the main treatment for advanced non­small­cell lung cancer (NSCLC), and epidermal growth factor receptor­tyrosine kinase inhibitors (EGFR­TKIs) have greatly improved the survival of patients with EGFR­sensitive mutations. However, there is no standard therapy for treating patients who are EGFR­TKI resistant. Combining EGFR­TKIs and platinum­based chemotherapy is the most popular strategy in the clinical practice. However, the synergistic mechanism between EGFR­TKIs and platinum remains unknown. Therefore, the aim of the present study was to determine the synergistic mechanism of gefitinib (an EGFR­TKI) and cisplatin (a main platinum­based drug). MTT assay, apoptosis analysis, tumorsphere formation and an orthotropic xenograft mouse model were used to examine the combination effects of gefitinib and cisplatin on NSCLC. Co­immunoprecipitation and immunofluorescence were used to identify the underlying mechanism. It was found that gefitinib could selectively inhibit EGFR from entering the nucleus, decrease DNA­PK activity and enhance the cytotoxicity of cisplatin on NSCLC. Collectively, the results suggested that inhibition of DNA­dependent protein kinase by gefitinib may be due to the synergistic mechanism between gefitinib and cisplatin. Thus, the present study provides a novel insight into potential biomarkers for the selection of combination therapy of gefitinib and cisplatin.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/pharmacology , DNA-Activated Protein Kinase/antagonists & inhibitors , Gefitinib/pharmacology , Lung Neoplasms/drug therapy , Animals , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cisplatin/administration & dosage , DNA-Activated Protein Kinase/metabolism , Drug Resistance, Neoplasm , Drug Synergism , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Female , Gefitinib/administration & dosage , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mice , Mice, Nude , Mutation , Proto-Oncogene Proteins p21(ras)/metabolism , Xenograft Model Antitumor Assays
7.
Mol Clin Oncol ; 9(4): 472-476, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30214735

ABSTRACT

At present, research on BRAF gene mutations appears to be mainly focused on melanoma rather than non-small-cell lung cancer (NSCLC). We herein describe the case of a patient with BRAF V600E-mutated advanced NSCLC, whose symptoms were relieved and computed tomography imaging revealed partial response to vemurafenib following failure of chemotherapy. This case demonstrates the promising prospects of BRAF inhibitor treatment in patients with BRAF-mutated NSCLC. Targeted therapies have significantly modified the treatment of NSCLC. However, tumor tissue is frequently hard to obtain, whereas the coincidence rate of gene mutations between the plasma and tumor tissue is 60-80%. Therefore, in cases where tumor tissue is difficult to obtain, plasma next-generation sequencing may be used to detect gene mutations, which can overcome the limitations of gene detection. Furthermore, due to the tumor heterogeneity, different patients exhibit different gene mutation abundance. Research has demonstrated that mutation abundance is associated with the therapeutic efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors. However, the association between BRAF mutation abundance and the therapeutic effect of BRAF inhibitors requires further verification.

8.
Oncol Lett ; 14(3): 3473-3479, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28927102

ABSTRACT

Glioma is the most common type of primary brain tumor, which is associated with a poor prognosis due to its aggressive growth behavior and highly invasive nature. Research regarding glioma pathogenesis is expected to provide novel methods of adjuvant therapy for the treatment of glioma. The use of bioinformatics to identify candidate genes is commonly used to understand the genetic basis of disease. The present study used bioinformatics to mine the disease-related genes using gene expression profiles (GSE50021) and dual-channel DNA methylation data (GSE50022). The results identified 17 methylation sites located on 33 transcription factor binding sites, which may be responsible for downregulation of 17 target genes. glutamate metabotropic receptor 2 was one of the 17 downregulated target genes. Furthermore, inositol-trisphosphate 3-kinase A (ITPKA) was revealed to be the gene most associated with the risk of glioma in children. The protein coded by the ITPKA gene appeared in all risk sub-pathways, thus suggesting that ITPKA was the gene most associated with the risk of glioma, and inositol phosphate metabolism may be a key pathway associated with glioma in children. The identification of specific genes helps to determine the pathogenesis and possible therapeutic targets for the treatment of glioma in children.

9.
World J Surg Oncol ; 12: 317, 2014 Oct 15.
Article in English | MEDLINE | ID: mdl-25315150

ABSTRACT

BACKGROUND: Attention dysfunction has been observed among many kinds of nervous system diseases, including glioma. This study aimed to investigate the correlation between glioma localization, malignancy, postoperative recovery time and attention deficit. METHODS: A total of 45 patients with glioma who underwent surgical resection and 18 healthy volunteers were enrolled. The attention network test, digital span test, color trail test II and Stroop test were used to detect the characteristics of attention deficit. RESULTS: Orientation network dysfunction was detected in the parietal lobe tumor group, and execution network deficit was detected in both the frontal and parietal lobe groups, while no significant difference was detected in the temporal lobe group compared to healthy controls. The high-grade glioma group (grade III-IV) exhibited more serious functional impairment than the low-grade group (grade I-II). No significant correlation was observed between postoperative recovery time and attention impairment. CONCLUSIONS: High-grade glioma patients suffer more severe attention impairment. In addition, the frontal and parietal lobe glioma patients suffer attention dysfunction in dissimilar manner. These findings will provide important guidance on the care of glioma patients after therapy.


Subject(s)
Attention , Brain Neoplasms/surgery , Glioma/surgery , Parietal Lobe/surgery , Postoperative Complications/psychology , Temporal Lobe/surgery , Adult , Brain Neoplasms/pathology , Brain Neoplasms/psychology , Case-Control Studies , Executive Function , Female , Glioma/pathology , Glioma/psychology , Humans , Male , Middle Aged , Orientation , Psychological Tests
10.
Int J Oncol ; 45(4): 1479-88, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25070059

ABSTRACT

Normal fibroblasts produce extracellular matrix (ECM) components that form the structural framework of tissues. Cancer-associated fibroblasts (CAFs) with an activated phenotype mainly contribute to ECM deposition and construction of cancer masses. However, the stroma of breast cancer tissues has been shown to be more complicated, and the mechanisms through which CAFs influence ECM deposition remain elusive. In this study, we found that the activated fibroblast marker α-smooth muscle actin (α-SMA) was only present in the stroma of breast cancer tissue, and the CAFs isolated from invasive breast cancer sample remained to be activated and proliferative in passages. To further assess the difference between CAFs and normal breast fibroblasts (NFs), MALDI TOF/TOF­MS was used to analyze the secretory proteins of primary CAFs and NFs. In total, 2,903 and 3,023 proteins were identified. Mass spectrum quantitative assay and data analysis for extracellular proteins indicated that the CAFs produce less collagens and matrix-degrading enzymes compared with NFs. This finding was confirmed by western blot analysis. Furthermore, we discovered that reduced collagen deposition was present in the stroma of invasive breast cancer. These studies showed that although CAFs from invasive breast cancer possess an activated phenotype, they secreted less collagen and induced less ECM deposition in cancer stroma. In cancer tissue, the remodeling of stromal structure and tumor microenvironment might, therefore, be attributed to the biological changes in CAFs including their protein expression profile.


Subject(s)
Actins/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Collagen/metabolism , Fibroadenoma/metabolism , Fibroblasts/metabolism , Extracellular Matrix/metabolism , Female , Fibroadenoma/pathology , Fibroblasts/pathology , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Invasiveness , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Stromal Cells/metabolism , Stromal Cells/pathology , Tumor Microenvironment
11.
World J Gastroenterol ; 20(17): 5104-12, 2014 May 07.
Article in English | MEDLINE | ID: mdl-24803826

ABSTRACT

AIM: To verify that the T stage has greater weight than the N stage in the staging of colorectal cancer. METHODS: Open data from the Surveillance, Epidemiology, and End Results program were reviewed and analyzed according to the T stage, N stage, and patients' observed survival (OS). The relative weights of the T and N stages were calculated by multiple linear regressions based on their impact on survival. Risk scores for 25 TN categories were then calculated from the T and N stage relative weights, and a rearranged tumor node metastasis (TNM) staging system was proposed via a cluster analysis of the TN scores. RESULTS: Both T and N stages significantly affect the OS of patients with colorectal cancer. Moreover, the T stage has greater weight than the N stage in the TNM staging system of colorectal cancer. For colon cancer, the relative T and N stage weights were 0.58 and 0.42, respectively, and for rectal cancer, the relative T and N stage weights were 0.61 and 0.39, respectively. On the basis of cluster analysis of the TN scores, T1N1a was classified to stage I, and T2N1a-1b and T1N1b-2a were classified to stage II in our revised TNM staging system for both colon and rectal cancer. For colon cancer, T4bN0 was classified to stage IIIa, but for rectal cancer, it was classified to stage IIIb. CONCLUSION: As the T stage affects colorectal cancer survival more significantly than the N stage, the TNM staging should be revised by relative T stage weight.


Subject(s)
Colorectal Neoplasms/pathology , Neoplasm Staging/methods , Cluster Analysis , Colorectal Neoplasms/mortality , Humans , Linear Models , Predictive Value of Tests , Risk Factors , SEER Program , Survival Analysis , Time Factors , United States
12.
Tumour Biol ; 35(7): 6319-26, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24643685

ABSTRACT

Resistance has been reported to human epidermal growth factor receptor 2 (HER2)-targeted therapy with the tyrosine kinase inhibitor lapatinib and the antibody trastuzumab in metastatic gastric cancer. An alternative or complement might be to target the extracellular domain of HER2 with therapy-effective radionuclides. The fraction of patients with HER2 expression in primary tumors and major metastatic sites, e.g., lymph nodes and liver, was analyzed to evaluate the potential for such therapy. Samples from primary tumors and lymph node and liver metastases were taken from each patient within a few hours, and to our knowledge, such sampling is unique. The number of analyzed cases was therefore limited, since patients that had received preoperative radiotherapy, chemotherapy, or HER2-targeted therapy were excluded. From a large number of considered patients, only 29 could be included for HER2 analysis. Intracellular mutations were not analyzed since they are assumed to have no or minor effect on the extracellular binding of molecules that deliver radionuclides. HER2 was positive in nearly 52 % of the primary tumors, and these expressed HER2 in corresponding lymph node and liver metastases in 93 and 100 % of the cases, respectively. Similar values for primary tumors and also good concordance with metastases have been indicated in the literature. Thus, relevant radionuclides and targeting molecules for nuclear medicine-based noninvasive, whole-body receptor analysis, dose planning, and therapy can be applied for many patients; see "Discussion" Hopefully, more patients can then be treated with curative instead of palliative intention.


Subject(s)
Biomarkers, Tumor/biosynthesis , Liver Neoplasms/genetics , Receptor, ErbB-2/biosynthesis , Stomach Neoplasms/genetics , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Biomarkers, Tumor/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Liver Neoplasms/pathology , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Lymph Nodes/pathology , Lymphatic Metastasis/genetics , Male , Middle Aged , Molecular Targeted Therapy , Neoplasm Staging , Radioisotopes/administration & dosage , Receptor, ErbB-2/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/radiotherapy , Trastuzumab
13.
Bioorg Med Chem ; 22(18): 5097-109, 2014 Sep 15.
Article in English | MEDLINE | ID: mdl-24398384

ABSTRACT

In search of new compounds with strong antiproliferative activity and simple molecular structure, we designed a novel series of agents based on the 2-amino-3-alkoxycarbonyl/cyano-5-arylethylthiophene scaffold. The presence of the ethyl spacer between the 2',5'-dimethoxyphenyl and the 5-position of the thiophene ring, as well as the number and location of methoxy substitutents on the phenyl ring, played a profound role in affecting the antiproliferative activity. Among the synthesized compounds, we identified the 2-amino-3-cyano-[2-(2,5-dimethoxyphenyl)ethyl] thiophene 2c as the most promising derivative against a wide panel of cancer cell lines (IC50=17-130 nM). The antiproliferative activity of this compound appears to correlate well with its ability to inhibit tubulin assembly and the binding of colchicine to tubulin. Moreover 2c, as determined by flow cytometry, strongly induced arrest in the G2/M phase of the cell cycle, and annexin-V and propidium iodide staining indicate that cell death proceeds through an apoptotic mechanism that follows the intrinsic mitochondrial pathway.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Thiophenes/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Mice , Models, Molecular , Molecular Structure , Polymerization/drug effects , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Thiophenes/chemical synthesis , Thiophenes/chemistry , Tubulin/metabolism
14.
Int J Clin Exp Med ; 7(12): 5686-90, 2014.
Article in English | MEDLINE | ID: mdl-25664091

ABSTRACT

The abnormal metabolic processes following traumatic brain injury (TBI) have been proposed to contribute to secondary injuries after TBI. Therefore, enteral nutrition (EN) support for TBI patients has received more attention. This study aimed to evaluate the complimentary effects of enteral nutrition with glutamine and hyperbaric oxygen (HBO) on the recovery of TBI. TBI model was established in SD rats, which were randomly divided into four groups: TBI, TBI + HBO, TBI + GLN, and TBI + HBO + GLN. Neuronal apoptosis in penumbra area was detected by TUNEL. Serum prealbumin level was detected by ELISA. Motor function was evaluated by beam-balance test. We found that the body weight of the rats had no significant differences in different groups before and after injury. Among the four groups, beam-balance test score was the lowest, serum prealbumin level was the highest, and neuronal apoptosis rate was the lowest in TBI + HBO + GLN group on day 3 and 7 after TBI. In conclusion, our data suggest that hyperbaric oxygen combined with enteral nutrition support with glutamine is effective in reducing neuronal apoptosis, increasing serum prealbumin concentration and improving neurological function after TBI injury.

15.
J Med Chem ; 56(22): 9296-309, 2013 Nov 27.
Article in English | MEDLINE | ID: mdl-24164557

ABSTRACT

The biological importance of microtubules make them an interesting target for the synthesis of antitumor agents. The 2-(3',4',5'-trimethoxybenzoyl)-5-aminobenzo[b]thiophene moiety was identified as a novel scaffold for the preparation of potent inhibitors of microtubule polymerization acting through the colchicine site of tubulin. The position of the methoxy group on the benzo[b]thiophene was important for maximal antiproliferative activity. Structure-activity relationship analysis established that the best activities were obtained with amino and methoxy groups placed at the C-5 and C-7 positions, respectively. Compounds 3c-e showed more potent inhibition of tubulin polymerization than combretastatin A-4 and strong binding to the colchicine site. These compounds also demonstrated substantial antiproliferative activity, with IC50 values ranging from 2.6 to 18 nM in a variety of cancer cell lines. Importantly, compound 3c (50 mg/kg), significantly inhibited the growth of the human osteosarcoma MNNG/HOS xenograft in nude mice.


Subject(s)
Antimitotic Agents/chemical synthesis , Antimitotic Agents/pharmacology , Thiophenes/chemical synthesis , Thiophenes/pharmacology , Animals , Antimitotic Agents/chemistry , Antimitotic Agents/toxicity , Apoptosis/drug effects , Caspases/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Chemistry Techniques, Synthetic , Colchicine/metabolism , Enzyme Activation/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice , Mice, Inbred BALB C , Mitochondria/drug effects , Models, Molecular , Protein Multimerization/drug effects , Protein Structure, Quaternary , Proto-Oncogene Proteins c-bcl-2/metabolism , Thiophenes/chemistry , Thiophenes/toxicity , Tubulin/chemistry , X-Linked Inhibitor of Apoptosis Protein/metabolism , Xenograft Model Antitumor Assays
16.
Health Qual Life Outcomes ; 11: 123, 2013 Jul 23.
Article in English | MEDLINE | ID: mdl-23875650

ABSTRACT

BACKGROUND: Rural-to-urban female migrant workers have a lower quality of life compared to the general population. Improving these conditions remains highly challenging. This paper reports the health-related quality of life (HRQoL) of the female migrant workers in an educational project. METHODS: In this before-and-after study, a community-based health education intervention was developed to improve female migrant workers' HRQoL and job satisfaction. A factory was selected as the location to implement the trial, using a before-and-after design. The education intervention included distribution and free access to study materials, monthly lectures, and counseling. The primary endpoint was HRQoL, and gynecological disease and job satisfaction were secondary endpoints. We assessed HRQoL at baseline and at 6-month follow-up using the Health Survey Short Form (SF-36). RESULTS: Compared to the baseline assessment, the participants at the 6-month survey reported higher General Health scores (standardized-ß coefficients (Betas) of ß = 0.056; P <0.001), Vitality scores (ß = 0.066; P <0.001), Mental Health scores (ß = 0.062; P <0.001), mental component summary scores (ß = 0.040; P <0.001), and job satisfaction (Odds Ratio [OR] 2.104, 95% confidence interval [CI] 1.837-2.408; P <0.01). CONCLUSIONS: A community-based educational intervention, targeted at female migrant workers, appears effective in improving HRQoL and job satisfaction.


Subject(s)
Job Satisfaction , Quality of Life , Rural Population/statistics & numerical data , Transients and Migrants/psychology , Urban Population/statistics & numerical data , Women, Working , Adult , China/epidemiology , Female , Health Status Indicators , Health Surveys , Humans , Middle Aged , Surveys and Questionnaires
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 21(1): 78-81, 2013 Feb.
Article in Chinese | MEDLINE | ID: mdl-23484696

ABSTRACT

This study was aimed to investigate the effect of homoharringtonine (HHT) on K562 cell proliferation, apoptosis and expression of BCL-2 and NF-κB proteins. The cells proliferation was assayed with MTT method, the cell apoptosis, cell cycle and BCL-2 expression were analyzed with flow cytometry, NF-κB protein expression was detected with Western blot. The results showed that HHT concentration-dependently inhibited proliferation of K562 cells, the IC50 at 48 h was 43.89 ng/ml. Treated with HHT 10 ng/ml for 48 h, K562 cell apoptosis significantly increased, cell cycle was blocked at G0/G1, the expression level of BCL-2 and NF-κB proteins was lower than that in control group (P < 0.05). It is concluded that HHT may inhibit the proliferation of K562 cells, and down-regulating expression levels of BCL-2 and NF-κB may be one of its anti-CML mechanisms.


Subject(s)
Harringtonines/pharmacology , NF-kappa B/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Flow Cytometry , Homoharringtonine , Humans , K562 Cells
18.
J Med Chem ; 55(11): 5433-45, 2012 Jun 14.
Article in English | MEDLINE | ID: mdl-22578111

ABSTRACT

A new series of tubulin polymerization inhibitors based on the 2-aryl/heteroaryl-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole scaffold was synthesized and evaluated for growth inhibition activity on a panel of cancer cell lines, cell cycle effects, and in vivo potency. Structure-activity relationships were elucidated with various substitutions at the 2-position of the thiazole skeleton. Hydrophobic moieties, such as phenyl and 3-thienyl, were well tolerated at this position, and variation of the phenyl substituents had remarkable effects on potency. The most active compound (3b) induced apoptosis through the mitochondrial pathway with activation of caspase-3. We also showed that it has potential antivascular activity since it reduced in vitro endothelial cell migration and disrupted capillary-like tube formation at noncytotoxic concentrations. Furthermore, compound 3b significantly reduced the growth of the HT-29 xenograft in a nude mouse model, suggesting that 3b is a promising new antimitotic agent with clinical potential.


Subject(s)
Antineoplastic Agents/chemical synthesis , Thiazoles/chemical synthesis , Thiophenes/chemical synthesis , Tubulin Modulators/chemical synthesis , Angiogenesis Inhibitors/chemical synthesis , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Caspase 3/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Endothelial Cells/drug effects , Endothelial Cells/physiology , Enzyme Activation , Humans , Hydroxybenzoates/chemical synthesis , Hydroxybenzoates/chemistry , Hydroxybenzoates/pharmacology , Mice , Mice, Nude , Mitochondria/drug effects , Mitochondria/physiology , Models, Molecular , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Thiazoles/chemistry , Thiazoles/pharmacology , Thiophenes/chemistry , Thiophenes/pharmacology , Transplantation, Heterologous , Tubulin Modulators/chemistry , Tubulin Modulators/pharmacology
19.
Hepatogastroenterology ; 59(118): 1699-705, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22626787

ABSTRACT

BACKGROUND/AIMS: To evaluate the safety and practicability of laparoscopic gastrectomy (LG) by comparing the short-term and long-term outcomes of LG and open gastrectomy (OG) for gastric cancer. METHODOLOGY: According to the criterion, randomized clinical trials (RCTs) were searched in MEDLINE, EMBASE, CNKI (in Chinese), WANFANG DATA (in Chinese), and Cochrane Controlled Trials Register from January 2000 to January 2012. The RCTs were prepared in accordance with the quality of reporting of meta-analyses statement. Intraoperative and early postoperative parameters, as well as long-term tumor recurrence were analyzed. Random effect meta-analyses were performed using odds ratios (ORs) and weighted mean differences (WMDs). RESULTS: Up to 8 RCTs with 782 patients were enrolled in the present meta-analysis (402 patients underwent LG (LG group) and 380 underwent OG (OG group)). The LG group had shorter wound lengths, less blood loss, more rapid bowel function recovery: first flatus and first food intake, lower overall complication rate and shorter hospital stay, whereas the LG group had longer operation times and less harvested lymph nodes. The tumor recurrence between the two groups had no significant difference. CONCLUSIONS: Considering its lower morbidity and enhanced postoperative recovery, LG is a safe technical alternative to OG for distal gastric cancer.


Subject(s)
Gastrectomy/methods , Laparoscopy , Stomach Neoplasms/surgery , Gastrectomy/adverse effects , Humans , Laparoscopy/adverse effects , Odds Ratio , Postoperative Complications/etiology , Randomized Controlled Trials as Topic , Recovery of Function , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
20.
Qual Life Res ; 21(3): 495-503, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21695594

ABSTRACT

BACKGROUND: Rural-urban female migrant workers living in factories are a special majority group in the city of Shenzhen, China. These female workers came from different provinces of mainland China. The health-related issues and quality of life (QOL) of this migrator have become serious public health and social problems, which have not been well characterized. This study aimed to explore the QOL and related factors of rural-urban female migrant workers living in factories in China. METHODS: In total, 3,622 rural-urban female migrant workers completed the Health Survey Short Form (SF-36). Sociodemographic characteristics, health status and job satisfaction during the past 6 months were also collected. RESULTS: Subjects had an average of 2.53 ± 1.93 (median = 2.00, quartile interval = 3.00) diseases. The two-week Morbidity Rate was 21.9%, and only 14.0% of the subjects were satisfied with their current job. Compared to Chinese female norms, the participants scored lower in seven concepts domains of SF-36 (role physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health). Multiple stepwise linear regression analysis showed that after adjustment for age, education level, work duration and job satisfaction, two-week Morbidity Rate, anemia symptoms and muscular soreness proved to be significant predictors for all the 7 domains (except for physical functioning). Digestive system disease was a significant predictor in 5 out of 7 domains, while urinary system disease and gynecological disease were significant predictors in 4 out of 7 domains. CONCLUSIONS: In general, QOL in rural-urban female migrant workers was lower than Chinese female norms. Improving their job satisfaction and controlling job-related disease appears to be critical to improving their QOL.


Subject(s)
Quality of Life , Surveys and Questionnaires , Transients and Migrants , Adolescent , Adult , China , Cross-Sectional Studies , Female , Health Status Indicators , Humans , Interviews as Topic , Job Satisfaction , Linear Models , Rural Population , Socioeconomic Factors , Urban Population
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