Sino Swed Molecular Bio Medicine Research Institute

Shenzhen, China

Sino Swed Molecular Bio Medicine Research Institute

Shenzhen, China
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Lou X.,Fudan University | Zhou J.,Sino Swed TongKang Bio Technology Inc. | Ma H.,Sino Swed Molecular Bio Medicine Research Institute | Xu S.,Sino Swed Molecular Bio Medicine Research Institute | And 4 more authors.
Genetic Testing and Molecular Biomarkers | Year: 2017

Aims: In this meta-analysis, we evaluated the usefulness of serum thymidine kinase 1 concentration (STK1c) for monitoring the outcome of extensive open surgery in patients with lung cancer. We also compared STK1c between a healthy population and patients with benign and malignant lung tumors to assess its potential value for early detection of lung cancer and for distinguishing between benign lung disease and malignant cancer. Materials and Methods: Related studies were retrieved from publications in PubMed, Cochrane, China National Knowledge Infrastructure, Wanfang databases, and Internet searches. Correlation was evaluated using weighted mean difference. Fixed or random effect models were selected for data analyses based on heterogeneity tested with the chi-square test. Publication bias was assessed using a funnel plot and Egger's test. Results: Twenty studies were selected for analysis, which showed that STK1c was significantly (p < 0.00001) reduced by 41.7% 1 month after extensive open surgery, approximately corresponding to an STK1c half-life of 1 month. STK1c levels were significantly higher in lung cancer patients than in healthy persons (p < 0.00001) or in patients with benign lung disease (p < 0.00001). There was also a significant difference in STK1c between patients with benign and malignant lung disease (p < 0.0001). Conclusions: The half-life of STK1c may be an important tool in the clinical evaluation of surgical response in patients with lung cancer. STK1c may also be beneficial in the early detection of lung cancer. © Mary Ann Liebert, Inc. 2017.

PubMed | PLA 180 Hospital and Sino Swed Molecular Bio Medicine Research Institute
Type: Journal Article | Journal: Cancer biomarkers : section A of Disease markers | Year: 2016

The World Health Organization (WHO) has estimated that the number of cancer patients will increase by about 70% during the next 25 years world-wide. To deal with this problem, WHO has suggested a focus on prevention of tumor incidence and health screening for early detection of people with tumors.To investigate the use of thymidine kinase 1 (TK1), CEA and AFP in serum to discover people with malignant tumors through health cancer screening.Of a cohort in 486,085 people of a routine health screening at the Health Centre, Fujun 180 Hospital, Quanzhou city, China, 56,286 people were investigated according to the presence of cancer during 2009-2014. The concentration of CEA and AFP were determined by an electrochemiluminescence immunoassay from Roche Diagnostics e601GmbH and STK1 by a commercial kit based on an enhanced chemiluminescent dot blot assay.The cancer incident rate increased from 0.048/100,000 to 0.220/100,000. The most common types of tumors were those of the liver, cervix and lung. STK1 correlated to tumor growth rate, was more sensitive than CEA and AFP for discovering people with malignant tumors and more sensitive among people who had diagnosis of malignant tumor. STK1 was also a prognostic biomarker for death at 10-40 months follow-up, while CEA and AFP were not. A combination of these markers increased the sensitivity by about 30%.STK1 is a reliable biomarker for discovering people with malignant tumors in cancer screening.

Pan Z.-L.,PLA Hospital | Ji X.-Y.,PLA Hospital | Shi Y.-M.,Diba Wu Hospital | Zhou J.,Sino Swed Molecular Bio Medicine Research Institute | And 2 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2010

Purpose this study was performed to examine possible use of thymidine kinase 1 concentration in serum (STK1)for prognosis of non-Hodgkin's lymphoma patients followingchemotherapy treatment. Methods The STK1 levels of 37 patients were determined by enhanced chemiluminescent dot-blot assay on the day before chemotherapy, and on day 1 and day 28 after start of the treatment. The speciWcity and sensitivity was evaluated by Western blot with anti-TK1 IgY antibody and by receiver operating characteristic (ROC) analysis. Results Western blot and ROC analysis of TK1 in serum showed high speciWcity and sensitivity. The mean STK1 level of the non-Hodgkin's lymphoma patients was signiWcantly higher compared to healthy persons (p < 0.001). The mean STK1 level increased signiWcantly (p < 0.001) on day 1 and then declined, reaching on day 28 values corresponding to those of healthy persons. The mean STK1 values before treatment and at 1 and 28 days after start of the treatment also correlated signiWcantly with the clinical response (CR, PR and NR) and Wve-year survival. Conclusion Although the number of patients was limited in this study, TK1 in serum might possess an important reference value in the evaluation of treatment and prognosis of non-Hodgkin's lymphoma following chemotherapy. © Springer-Verlag 2010.

Xu Y.,Nanjing University | Xu Y.,Nanjing Southeast University | Liu B.,Nanjing University | Shi Q.-L.,Nanjing University | And 8 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2014

Objectives: The sensitivity and reliability of the biomarkers thymidine kinase 1 (TK1) and Ki-67 were studied in relation to clinical features and prognosis of survival for pathological-T1 (pT1) lung adenocarcinoma patients. Methods: TK1 and Ki-67 expression was determined in 80 patients with pT1 adenocarcinoma of the lung and in 20 specimens from normal lung tissues, using immunohistochemistry. Results: TK1 was found in most lung tumor cells both in the cytoplasm and the nuclei. The positive labelling index (LI) for total TK1 was significantly higher than that for Ki-67. There was a significant correlation between the LI of total TK1 and lymph node metastasis, degree of tumor invasion and pathologic stages, which was not found for Ki-67. In addition, the overall 5-year survival of patients was statistically significant different between low and high levels of TK1 expression, but not in cases of Ki-67. A multivariate analysis revealed that expression of TK1, lymph node involvement and TNM pathology staging could serve as independent prognostic factors for the disease progression of pT1 lung adenocarcinoma patients. Conclusions: Compared with Ki-67, TK1 is a more reliable proliferation index in pT1 adenocarcinoma of lung, which can evaluate the invasion and the prognosis of tumor. © 2014, E-Century Publishing Corporation. All rights reserved.

Luo P.,Wuhan University | Wang N.,Karolinska University Hospital | He E.,Karolinska University Hospital | He E.,Sino Swed Molecular Bio Medicine Research Institute | And 6 more authors.
Pathology and Oncology Research | Year: 2010

The activity of the proliferation related enzyme thymidine kinase 1 (TK1) was reported to be 3-fold higher in extracts from normal kidney tissue as compare to renal carcinoma extracts [3]. To verify these unexpected results, determinations of the protein levels of TK1 in normal kidney and in samples from different types of renal cell carcinoma (RCC) were done with immunohistochemistry and Western blot analysis. Two anti-TK1 peptide antibodies reacting with different TK1 epitops were used. TK1 levels were high in tubule cells as compared to glomerulus cells and connective tissue cells, while an intermediary TK1 was observed in renal cell carcinoma (RCC) cells. Western blot analysis demonstrated high levels of TK1 in extract from normal kidney, and lower levels of TK1 in the RCC extracts. The specificity of TK1 staining was demonstrated in competition experiments with excess TK1 antigen. The high TK1 levels in normal kidney tubule cells suggest that they are in a form of activated G1-state. The relatively low TK1 level in RCC, representing TK1 expression in S-phase cells, is in accordance with the low overall proliferation rate of these tumors. These results suggest that cell cycle regulation of TK1 in normal tubule cells differ from that in other type of normal and malignant renal cells. © Arányi Lajos Foundation 2009.

PubMed | Shenzhen Second Hospital, Central South University and Sino Swed Molecular Bio Medicine Research Institute
Type: Journal Article | Journal: Oncology letters | Year: 2015

With regard to different types of malignancies, thymidine kinase 1 (TK1) is a useful prognostic marker in clinical oncology, both as a serum proliferation marker and in immunohistochemistry. The present study investigated the use of serum TK1 protein (STK1p) for the identification of multiple proliferating diseases linked to the risk of developing cancer, by following one patient during the period of 2003-2014. The patient presented with adenomatous polyps in the stomach in 2003, follicular cervicitis in 2007 and hyperplasia of the breast/fibrocystic breasts in 2010. The breast cysts increased from 45 mm in size in 2010 to 87 mm in size in 2013, and were assessed as a suspicious malignancy at the end of this period. In parallel, the STK1p values increased from 2.0 to 7.6 pM. Based on this information, a minimally invasive surgery using the Mammotome Biopsy System was performed. Immunohistochemistry on the cyst tissue showed strong staining of TK1 in the ductal epithelial cells and thus confirmed the abnormal proliferation in the lesion. One week after the surgery, the STK1p value had decreased to almost normal values (1.6 pM), but then fluctuated above 2.0 pM for the next 7 months. After the surgery, the patient was re-examined and small foci with squamous cell hyperplasia and a suspected ulcerated cervix, as well as flat gastric erosive, were identified, but not treated; this may explain why the STK1 P-values did not return to within normal values. The patient is currently being followed up using STK1p analysis combined with imaging/pathology in order to begin therapeutic intervention as early as possible to avoid the risk of developing cancer. Overall, STK1p is useful in health screening to identify individuals at risk of developing premalignancy/malignancy.

Lou X.-D.,Fudan University | Wang H.-D.,Fudan University | Xia S.-J.,Fudan University | Xia S.-J.,Chongqing Medical University | And 2 more authors.
Archivum Immunologiae et Therapiae Experimentalis | Year: 2014

This paper studies the expression of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ and anti-inflammatory cytokines such as IL-10 in diabetic rat aortas, the effects of resveratrol on these cytokines, and the potential epigenetic mechanisms involved. The experiment was performed on rats divided into four groups: normal group (NC), normal interventional group (NB), diabetic group (DM), and diabetic interventional group (DB). The NB and DB groups were treated with resveratrol. After more than 3 months, the rats' aortas were removed and analyzed for cytokines by using immunohistochemistry, Western blotting, real-time PCR, and methylation-specific PCR. Histological localization of these cytokines was mainly found in the arterial intima of diabetic rats. The protein and mRNA expression levels of IL-1β, IL-6, TNF-α, and IFN-γ were significantly higher in the DM group than in the NC group (p < 0.05), whereas in the resveratrol-treated groups (NB and DB), the levels were relatively lower than those in the corresponding groups. The DM group showed reduced levels of DNA methylation at the specific cytosine phosphate guanosine sites of IL-1β, IL-6, TNF-α, and IFN-γ, relative to those in the NC group (p < 0.01), and these levels were increased by resveratrol. In contrast, IL-10 was dramatically methylated and showed decreased expression in response to high glucose, and resveratrol reversed this effect. These results demonstrate that the inflammatory response is involved in diabetic macroangiopathy. Resveratrol inhibits the expression of proinflammatory cytokines and thus may have a protective effect on the aorta in hyperglycemia. Thus, DNA methylation, an epigenetic gene silencing signal, may be responsible for these two phenomena. © 2014 L. Hirszfeld Institute of Immunology and Experimental Therapy.

Xu Y.,Nanjing Medical University | Shi Q.-L.,Nanjing Medical University | Ma H.,Nanjing Medical University | Zhou H.,Nanjing Medical University | And 8 more authors.
Tumor Biology | Year: 2012

In this study, we explore the association of thymidine kinase 1 (TK1) expression in tumour tissues with clinical pathological parameters and prognosis in patients with pathological T1 (pT1) lung adenocarcinoma. The expression of TK1 was studied by immunohistochemistry techniques in 80 patients with surgically resected pT1 lung adenocarcinoma, retrospectively and at >10-year follow-up. Compared to patients with low TK1 expression [labelling index (LI) <25.0%], patients with high TK1 expression (LI ≥25.0%) showed significantly increased lymphatic/vascular permeation and lymph node involvement and higher stromal invasion grade and pathological stage, and a greater number of patients had a tumour size of 2.1 to 3.0 cm. The 5-year survival and the mortality during follow-up for patients with high TK1 expression were significantly worse than that of patients with low TK1 expression. The prognoses of the cases with grade 0, grade 1 and grade 2 stromal invasions were similar and were better than those of cases with grade 3. In patients with stromal invasion grade 3, the 5-year survival and the mortality during follow-up were significantly worse for patients with high TK1 compared to patients with low TK1 expression. Univariate analyses showed that stromal invasion and TK1 expression were significant prognostic factors, while in the multivariate analysis, TK1 expression and tumour stage were found to be independent prognostic factors, but not stromal invasion. This is the first study showing that TK1 expression in combination with stromal invasion is a more reliable prognostic factor than stromal invasion classification itself in patients with pT1 lung adenocarcinoma. TK1 expression enables a further classification of the patients and opens opportunities for improved treatment outcome. © International Society of Oncology and BioMarkers (ISOBM) 2011.

Li Z.,Chinese Academy of Sciences | Wang Y.,Chinese Academy of Sciences | He J.,Chinese Academy of Sciences | Ma J.,Chinese Academy of Sciences | And 6 more authors.
European Journal of Cancer Prevention | Year: 2010

In this study we examine the use of the concentration of thymidine kinase 1 in serum (STK1) as a prognostic factor in routine clinical settings. For this purpose we used sera from patients with oesophageal (n=101) and cardial (n=39) carcinomas and nonsmall-cell lung carcinoma (NSCLC) (n=157). Sera from healthy individuals (n=95) were used as controls. STK1 was analysed by a chemiluminiscence dot blot assay. The mean STK1 concentrations and the STK1 positive rates of the patients with oesophageal and cardial carcinomas and with NSCLC were significantly higher as compared with healthy controls (P=0.01). The mean STK1 value of oesophageal carcinoma patients correlated with T-values (P=0.021) and with stage (P<0.005), but not with grade. The mean STK1 value of cardial carcinoma patients did not correlate with grade. No data on stage and T-values were available for these patients, due to advanced disease. The mean STK1 value of NSCLC patients with squamous cell carcinoma was significantly higher as compared with adenocarcinoma type (P=0.024). The mean STK1 value of the NSCLC patients correlated with clinical grade (P=0.006), T-values (P=0.001), stage (P=0.035) and to size of the tumour (P=0.030). The mean STK1 value and the number of STK1 positive patients were also higher in recurrent NSCLC patients. There was a tendency that stage I-II NSCLC patients with an STK1 level above 2 pmol/l showed a higher frequency of recurrence/death than patients below 1 pmol/l. Our results show that STK1 is a useful marker for prognosis in patients with oesophageal, cardial and lung carcinomas. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Lou X.-D.,Fudan University | Wang H.-D.,Fudan University | Xia S.-J.,Fudan University | Skog S.,Sino Swed Molecular Bio Medicine Research Institute
Fudan University Journal of Medical Sciences | Year: 2014

Diabetes mellitus and its associated micro- and macrovascular complications have posed a great threat to public health and become the main cause of morbidity and mortality burden to state economy. Recent studies have raised that epigenetics may play an important role in the pathology of diabetic vascular diseases, which refers to phenotype changes that are not related to the underlying DNA sequence, yet the alterations in gene expression can possibly be inherited into next generation. Furthermore, UKPDS and DCCT-EDIC demonstrate a phenomenon called metabolic memory, even if the blood glucose level is controlled in an ideal state, vascular inflammation still persists. Although epigenetics has not been fully elucidated, it provides a new insight into the pathogenesis of diabetes and is expected to become the targeted therapy for severe diseases.

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