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Journal of International Translational Medicine
Journal of International Translational Medicine
JITM, ISSN 2227-6394
founded in 2012
Editor-in-chief:Feng Jifeng, China
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2015 Vol. 3, No. 2
Published: 15 June 2015

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Expression of Caspase-3 in Laryngeal Squamous Cell Carcinoma and its Relationship with Cell Apoptosis

YU Yuan-chen, ZHONG Zhao-kun, LI Ji-xia, YU Chuan-ting
Journal of International Translational Medicine, 2015, 3(2): 72-76 | doi:10.11910/2227-6394.2015.03.02.01
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Objective: To investigate the expression ofCaspase-3 in laryngeal squamous cell carcinoma (LSCC) and its relationship with cell apoptosis. Methods: The expression of Caspase-3 protein in 43 LSCC tissues and 21 vocal cord polyp tissues was detected using immunohistochemical SP method; the apoptosis of LSCC was measured by in situ end-labeling (TUNEL) assay, and the relationships between Caspase-3 expression and clinicopathological features as well as cell apoptosis in LSCC tissue were analyzed. Results: The positive rate of Caspase-3 expression in LSCC tissue was lower than in vocal cord polyp tissue dramatically, with statistical significance (51.2% vs. 85.7%, P=0.007). Caspase-3 expression in LSCC tissue was closely related to the tumor differentiated degrees, clinical staging and presence or absence of lymph node metastasis (P=0.009, 0.001, 0.018) instead of the gender, age and tumor size (P>0.05). The apoptosis index (AI) of Caspase-3 was (4.31±0.49)% in LSCC tissue, while (24.28±1.07)% in vocal cord polyp tissue. Significant difference was presented between two groups by comparison to the AI (P<0.001). Spearman correlation analysis displayed that Caspase-3 expression in LSCC tissue had a significantly positive correlation with the number of positive TUNEL cells (r=0.435, P=0.000). Conclusion: Low expression of Caspase-3 protein might promote the tumorigenesis and progression by reducing the apoptosis of tumor cells, and detection to its protein can be considered as an important index for judging the differentiation, clinical staging, infiltration and metastasis of laryngeal carcinoma.

Expression of p16 in Human Colorectal Cancer and Its Clinical Significance Hot!

HE Qian-qian
Journal of International Translational Medicine, 2015, 3(2): 77-80 | doi:10.11910/2227-6394.2015.03.02.02
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Objective: To explore the expression of p16 in human colorectal cancer and its clinical significance. Methods: Neoplastic tissues and autologous non-neoplastic tissues were taken from 30 patients with colorectal cancer immediately after the operation. The expression of p16 in these tissues was detected using immunohistochemistry, and then was confirmed with HT-29 cell line by Western-blot assay. Results: The positive rate of p16 expression in neoplastic tissues was 23.3%, significantly lower than that in non-neoplastic tissues (P<0.01). p16 expression was closely associated with Dukes’ staging (P<0.01), lymph node metastasis(P<0.05) and histological differentiation degrees (P<0.05). And western-blot assay showed that the p16 expression in HT-29 cells was consistent with that of human colorectal cancer. Conclusion: Abnormal expression of p16 may play an important role in the occurrence and progression of colorectal cancer, and hence, it would be associated with the prognosis of colorectal cancer.

Application of 18F-FDG PET/CT in Rare Metastatic Locations of Esophageal Carcinoma Hot!

MA Lan, GUAN Dan, DING Qi-yong, SHU Yong-qian, LIU Lian-ke
Journal of International Translational Medicine, 2015, 3(2): 86-92 | doi:10.11910/2227-6394.2015.03.02.04
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Background: Esophageal carcinoma is a kind of malignant tumor commonly seen in clinic. In recent years, positron emission tomography (PET)/CT can accurately locate the general tumor nidi and PET/CT detection is recommended to determine the clinical stages of esophageal carcinoma. The common metastatic locations of esophageal carcinoma include lymph nodes (including cervical, supraclavicular and celiac lymph nodes), lung, liver and bone. This study aimed to summarize the distribution and incidence of rare metastatic locations and the characteristics of 18F-FDG PET/CT image in patients with esophageal carcinoma. Methods: A total of 185 patients with esophageal carcinoma undergoing 18F-FDG PET/CT detection in our hospital from August, 2009 to August, 2013 were collected to retrospectively analyze their clinical data. Metastatic nidi in rare locations were confirmed according to the results of clinical evaluation, imageological methods and follow-up. Results: A total of 19 patients with esophageal carcinoma suffered from metastases in rare locations according to the 18F-FDG PET/CT detection, with incidence of 10.27%. The rare locations included pleura (28.6%), peritoneum (23.8%), adrenal gland (1.6%), axillary lymph nodes (14.3%), nasal septum (4.8%), cerebellum (4.8%) and napes (4.8%). Conclusion: 18F-FDG PET/CT detection can excellently detect the metastatic nidi in rare or uncommon locations and increase the accuracy of clinical staging and re-staging in patients with esophageal carcinoma, which has great guiding significance for clinical therapy.

Translational Medicine Study on Circulating Tumor Cell Detection in Patients with Metastatic Breast Cancer Hot!

SHEN Bo, ZHENG Ma-qing, XU Xin-yu, WEI Da
Journal of International Translational Medicine, 2015, 3(2): 93-97 | doi:10.11910/2227-6394.2015.03.02.05
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Objective: To explore the prognostic and predictive effects of circulating tumor cell (CTC) detection in patients with metastatic breast cancer (MBC). Methods: A total of 139 patients with MBC were selected to detect the peripheral blood CTC count by CellSearch system. The survival analysis was conducted according to CTC count, and multivariate Cox regression analysis was performed to analyze the factors influencing the progression-free survival (PFS), so as to diagnose the prognostic and predictive effects of CTC counts on MBC patients. Results: The rates of patients with CTC count ≥5 were 38.85% (54/139), 22.43% (24/107) and 17.27% (19/110) before treatment, 3-4 weeks after treatment and 6-8 weeks after treatment, respectively. Before treatment, the PFS of patients with CTC count ≥5 was evidently lower than those with CTC count <5, which difference was more significant along with time. HR coefficients of CTC to PFS were 1.939, 2.401 and 3.726 before treatment, 3-4 weeks after treatment and 6-8 weeks after treatment, respectively. And CTC was superior to estrogen receptor (ER) or progesterone receptor (PR) condition, human epidermal receptor 2 (HER2) condition and Eastern Cooperative Oncology Group (ECOG) score in the prognostic and predictive values of MBC patients. Conclusion: CTC count can better reflect the therapeutic efficacy, and has higher clinical predictive value in the PFS of MBC patients.

Relationship between Polymorphism of HLA-DP Gene and Susceptibility Hepatitis C Infection Hot!

WANG Jia,XIAO Rong-rong, SHEN Hong-bing
Journal of International Translational Medicine, 2015, 3(2): 98-102 | doi:10.11910/2227-6394.2015.03.02.06
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Objective: To assess the relationship between HLA-DP gene polymorphism and the susceptibility of HCV infection among high-risk populations in Jiangsu Province. Methods: Three HLA-DP variants of rs3077, rs9277535 and rs2395309 were genotyped in 1653 subjects including 268 self-limited HCV infection subjects, 401 persistent HCV infection subjects and 984 healthy control people using Taqman- MGB. Conclusion: These variants in the HLA-DP locus are associated with the susceptibility of HCV infection.Three HLA-DP variants of rs3077, rs9277535 and rs2395309 were genotyped in 1653 subjects including 268 self-limited HCV infection subjects, 401 persistent HCV infection subjects and 984 healthy control people using Taqman- MGB. Results: The frequencies of rs3077, rs9277535 and rs2395309 mutant genotype in HCV infected group were much higher than in control group (Prs3077<0.010; Prs9277535=0.043; Prs2395309<0.010); The frequencies of rs3077 TC and rs2395309 AG heterozygous genotypes were much higher than control group (Prs3077=0.033


Effect of Psychological Factors on the Level of Serum Vascular Endothelial Growth Factor in Patients with Gynecological Malignant Tumors

YU Cui-ge, LI Lian-xiang, LIU Xiao-qin, SHI Jian-yong
Journal of International Translational Medicine, 2015, 3(2): 103-108 | doi:10.11910/2227-6394.2015.03.02.07
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Objective: To investigate the effect of psychological factors on the level of serum vascular endothelial growth factor (VEGF) in patients with gynecological malignant tumors. Methods: Fifty-six patients with gynecological malignant tumors were selected as malignant tumor group in Shaanxi Provincial People’s Hospital from Jun. 2013 to Jun. 2014, and meanwhile, 56 healthy people were selected as control group at the same term. The life events, social support and coping styles of the subjects in both groups were given questionnaire survey based on life event scale (LES), social support rating scale (SSRS) and trait coping style questionnaire (TCSQ). The scores of LES, SSRS and TCSQ in two groups were compared, and the correlation between the level of serum VEGF and psychological factors in malignant tumor group was analyzed. Results: Both the frequency of negative events and total frequency of life events in malignant tumor group were higher than in control group dramatically (P=0.000, 0.000), while the scores of objective support, subjective support and availability to support lower than in control group (P=0.000, 0.000, 0.001). The scores of positive coping in malignant tumor group was notably lower than in control group, but those of negative coping higher than in control group (P=0.000, P=0.000). Pearson correlation analysis displayed that the level of serum VEGF was positively correlated with the frequency of negative events and scores of negative coping (r=0.828, P=0.000; r=0.944, P=0.000), while negatively correlated with the scores of positive coping, objective and subjective support (r=-0.921, P=0.000; r=-0.951, P=0.000; r=-0.899, P=0.000). Conclusion: Negative life events, low social support and bad coping styles can all promote the increase of VEGF level in patients with gynecological malignant tumors, and are closely associated with occurrence and progression of malignant tumors.

Comparative Study on Rituximab Combined with Chemotherapy and Single Chemotherapy for Diffuse Large B Cell Lymphoma Hot!

FENG Ji-feng
Journal of International Translational Medicine, 2015, 3(2): 109-113 | doi:10.11910/2227-6394.2015.03.02.08
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Objective: To explore the clinical efficacy and safety of rituximab combined with chemotherapy and single chemotherapy for diffuse large B cell lymphoma (DLBCL). Methods: A total of 97 patients with DLBCL were selected. Patients treated by single chemotherapy were designed as control group, while those by rituximab combined with chemotherapy as observational group. All patients were treated for at least 4 cycles. The short-term and long-term efficacy and related adverse reactions of 2 groups were observed. Results: The rate of complete remission (CR) in observational group was significantly higher than in control group (χ2=4.6589, P=0.0309). However, there was no significant difference in objective remission rate (ORR) between 2 groups (P=0.3651). The rates of 3-year overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were 80.30% (53/66), 69.70% (46/66) and 59.09% (39/66) in observational group, and 61.29% (19/31), 58.06% (18/31) and 58.06% (18/31) in control group, respectively. The OS in observational group was significantly longer than in control group (P=0.035). However, there was no significant difference in PFS, DFS and rate adverse reactions between 2 groups (P=0.089; P=0.438; χ2=0.1562, P=0.6927). Conclusion: Rituximab combined with chemotherapy can improve the efficacy of DLBCL without increasing the adverse reactions, which can be used as the first-line treatment for DLBCL, thus deserving to be widely applied in clinic.

Application of Translational Medicine Theory in Chinese Materia Medica: Effect and Mechanism of Mahuang and Wuweizi on Pulmonary Fibrosis Hot!

QIN Hai-zhi, DONG Wei-tao
Journal of International Translational Medicine, 2015, 3(2): 114-119 | doi:10.11910/2227-6394.2015.03.02.09
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Objective: To explore the effect and mechanism of Mahuang (Herba Ephedra) and Wuweizi (Schisandra Chinesis) on pulmonary fibrosis based on translation medicine theory. Methods: Totally 90 Wistar rats were divided into 6 groups. Pulmonary fibrosis models of rats were established by drip of bleomycin A5 through trachea while sham-operation group was infused with equivalent normal saline instead of bleomycin A5 into trachea. Sham-operation group and negative control group were performed with normal saline gavage while positive control group with subcutaneous injection of hydrocortisone, Mahuang group and Wuweizi group with gavage of Mahuang and Wuweizi concentrated decoctionα) were detected and compared. Results: All models of groups were successfully established. Compared with negative control group, the levels of VEGF, Ang-2, MCP-1 and MIP-1α decreased in different degrees but TSP-1 increased in other groups after medication for 7 days and 28 days. Conclusion: Mahuang and Wuweizi have intervention effects on pulmonary fibrosis, the mechanism of which might be related to the inhibition of excessive angiogenesis through inhibiting the expression of MCP-1 and MIP-1α, lowering the level of proangiogenic factors (Ang-2 and BEGF), and enhancing the level of angiogenesis inhibiting factor (TSP-1)., respectively, whereas combined group was treated with gavage of Mahuang concentrated decoction during the first 7 days and with Wuweizi concentrated decoction in the ensuing 21 days. On the 7th day and 28th day, pulmonary alveolitis and fibrosis in different groups were observed and the expression levels of serum vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), thrombospondin-1 (TSP-1), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1


Yaseen Ali, Amila M. Parekh, Rahul K. Rao, Mirza R. Baig
Journal of International Translational Medicine, 2015, 3(2): 120-122 | doi:10.11910/2227-6394.2015.03.02.10
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Chronic heart failure is one of the most common reasons for hospital admissions in the United States. A patient is diagnosed with heart failure when the heart is unable to do its physiological work of pumping the blood to the peripheral organs. At this time, the excess volume of fluid can accumulate easily, leading to signs of fluid overload. Loop diuretics has been at the forefront to alleviate these symptoms. It has its own side effects, but a lesser known and monitored is metabolic alkalosis. Herein, we reviewed a case where a patient developed metabolic alkalosis due to loop diuretics.

Targeted Therapies for Inflammatory Bowel Disease and Colorectal Cancer: An Increasing Need for Microbiota-Intestine Mutualism

Tomasello Giovanni, Tralongo Pietro, Jurjus Abdo, Hisham Daouk, Inaya Hajj Hussein, Matar Michel, Leone Angelo
Journal of International Translational Medicine, 2015, 3(2): 123-129 | doi:10.11910/2227-6394.2015.03.02.11
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The involvement of intestinal microbiota and dysbiosis in the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC) is a well-established fact to be taken into real consideration when developing tartgeted therapies. This review aimed to depict what advances in our understanding of the role of intestinal flora in the pathogenesis of IBD and CRC is shaping up the therapeutic protocols of their management. It was demonstrated that there is a circadian regulation of colocytes gene expression in response to microbiota. In addition, dysbiosis leading to a decrease in microbiome biodiversity was also described in IBD patients whereby thick layers of adherent mucosa associated bacteria exist both in ulcerative colitis (UC) and Crohn’s disease (CD). Probiotics based approaches using lactobacilli and Bibidobacteria improved clinical symptoms of IBD’s through the GALT immune modulation. In addition, fecal microbiota transplantation (FMT) has also been used for IBD treatment. It consists of transferring gastrointestinal microbiota from a healthy donor to an IBD patient by duodenal infusion of liquid stool suspension to establish microbial homeostasis. The passage of bacteria in the injured mucosal zone triggers chronic inflammation and eventually CRC development by creating a carcinogenic environment. Actually, high level of Fusobacterium nucleatun and other bacteria are prevalent in CRC patients, thus suggesting a potential role of these organisms in the initiation and progression processes due to the production of genotoxic metabolites causing a direct damage to DNA integrity. Moreover, regular probiotics intake was shown to actively prevent the whole process. In conclusion, the mutualistic relationship between microbiota and colonic mucosa proved useful in depicting some of the dynamics of the initiation and development of IBD and CRC. Therapies oriented towards establishing equilibrium of intestinal microbiota may represent the key strategy to switch off chronic inflammatory processes hitting colonic mucosa, thus preventing the onset of CRC.



Rajagopal Krishnamoorthy, Octavio Fernandes, Arturo Chiti, Rose Ann Padua
Journal of International Translational Medicine, 2015, 3(2): 130-135 | doi:10.11910/2227-6394.2015.03.02.12
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Disease markers are defined as the biomarkers with specific characteristics during the general physical, pathological or therapeutic process, the detection of which can inform the progression of present biological process of organisms. However, the exploration of disease markers is complicated and difficult, and only a few markers can be used in clinical practice and there is no significant difference in the mortality of cancers before and after biomarker exploration. Translational medicine focuses on breaking the blockage between basic medicine and clinical practice. In addition, it also establishes an effective association between researchers engaged on basic scientific discovery and clinical physicians well informed of patients’ requirements, and gives particular attentions on how to translate the basic molecular biological research to the most effective and appropriate methods for the diagnosis, treatment and prevention of diseases, hoping to translate basic research into the new therapeutic methods in clinic. Therefore, this study mainly summarized the exploration of disease markers under translational medicine model so as to provide a basis for the translation of basic research results into clinical application.


LIU Qiao
Journal of International Translational Medicine, 2015, 3(2): 136-144 | doi:10.11910/2227-6394.2015.03.02.13
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With the development of life sciences, people have changed their focus from local research to systematic biology, thus contributing to the development of a series of “omics”, including genomics, transcriptomics, proteomics and metabonomics, etc. Metabonomics is a presently developed new branch of science that can provide qualitative and quantitative analysis on all metabolites with low-molecular quality in the body, tissues or cells of an organism. It recognizes the changes and rules of the biological endogenous substance under the impact of internal and external factors by generally and quantitatively detecting multiple small molecular compounds in biological samples, in hope of finding out the metabolic marker clusters in the early stage of diseases so as to provide new pathways for the early diagnosis of the diseases and the realization of individualized drug administration. Additionally, metabonomics research on clinical diseases has become a hot topic and made great achievement in the developmental condition, diagnostic methods, pathogenic mechanism and pharmaceutical efficacy evaluation of diseases. This study mainly reviewed the application and advances of metabonomics in the early diagnosis of malignant tumors, cardiovascular and respiratory diseases, hoping to provide references and prompts for metabonomics-associated researches.

Interpretation of NCCN Guidelines: General Therapies on Non-small Cell Lung Cancer (Version 6. 2015) Hot!

HUANG Xin-en
Journal of International Translational Medicine, 2015, 3(2): 145-150 | doi:10.11910/2227-6394.2015.03.02.14
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Lung cancer is one of the most common malignant tumors in China and ranks the first of cancer-related death. The major etiological agent of lung cancer is an industry-made and promoted addictive product, so lung cancer is considered to be a unique disease in all cancers. Effective policies for public health are required to prevent the smoking initiation so as to reduce the mortality of lung cancer, so Food and Drug Administration (FDA) has introduced a series of measures to monitor the tobacco products. As to patients with strong suspicion of lung cancer in stage Ⅰ-Ⅱ, a preoperative biopsy is needed and intra-operative diagnosis is necessary before pneumonectomy, bilobectomy or lobectomy if the preoperative tissue diagnosis is not obtained. However, lung cancer still cannot be easily diagnosed and cured, so the annual improvement and update of new therapeutic protocols and the development of new agents is of great significance. Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancer, and above 75% NSCLC patients are in middle-advanced stage when diagnosed, so they have lost the optimal therapeutic opportunity and the 5-year survival rate is relatively low. Therefore, this study mainly interpreted the National Comprehensive Cancer Network (NCCN) guidelines on the general therapies on NSCLC, hoping to provide references for the treatment of NSCLC patients and prolong their long-term survival.
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