Background: The prognostic value of human epidermal growth factor receptor-2 (HER-2/neu) for survival of patients with colorectal cancer (CRC) is still ambiguous. We therefore performed a meta-analysis to evaluate its prognostic significance. Materials and Methods: We searched the MEDLINE and EMBASE databases for published literature investigating associations between HER-2/neu status and overall survival of patients with CRC. A meta-analysis was performed using a DerSimonian-Laird model and publication bias was investigated by Begg's and Egger's tests. Subgroup analysis was also conducted according to the study design type, study quality score, cut-off value for HER-2/neu overexpression, publication region, patient number and publication year. Results: A total of 17 eligible studies involving 2,347 patients were identified for this meta-analysis. The combined hazard ratio (HR) was 1.31 (95% confidence interval (CI): 0.96-1.79), suggesting that HER-2/neu overexpression was not significantly associated with overall survival of patients with CRC. However, subgroup analysis revealed that HER-2/neu overexpression had an unfavorable impact on survival when the analysis was restricted to subgroups of study quality score ${\leq}5 $(HR=1.56, 95%CI: 1.17-2.10), Asian patients (HR=1.74, 95%CI: 1.22-2.49), patient number ${\leq}106$ (HR=1.57, 95%CI: 1.01-2.44), publication year before 2003 (HR=1.59, 95%CI: 1.02-2.49), and prospectively designed study (HR=3.62, 95%CI: 1.42-9.24). The effect disappeared in subgroups of study quality scores > 5 (HR=0.69, 95%CI: 0.33-1.44), non Asian patients (HR=1.14, 95%CI: 0.77-1.70), patients' number > 106 (HR=1.07, 95%CI: 0.67-1.72), publication year after 2003 (HR=1.13, 95%CI: 0.76-1.69), and retrospectively designed study (HR=1.22, 95%CI: 0.89-1.67). Conclusions: Our meta-analysis suggests that HER-2/neu overexpression might not be a significantly prognostic indicator for patients with CRC. Further studies are required to confirm these results.
Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.
Ji Hwa Hong;Sang Hoon Kim;Hyun Gyung Kim;Jun Ho Jang;Ryeo Gang Son;Seung Pil Pack;Young-Ho Park;Philyong Kang;Kang-Jin Jeong;Ji-Su Kim;Hanbyeul Choi;Sun-Uk Kim;Yong Woo Jung
IMMUNE NETWORK
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v.21
no.3
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pp.24.1-24.13
/
2021
Due to the inconsistent fluctuation of blood supply for transfusion, much attention has been paid to the development of artificial blood using other animals. Although mini-pigs are candidate animals, contamination of mini-pig T cells in artificial blood may cause a major safety concern. Therefore, it is important to analyze the cross-reactivity of IL-7, the major survival factor for T lymphocytes, between human, mouse, and mini-pig. Thus, we compared the protein sequences of IL-7 and found that porcine IL-7 was evolutionarily different from human IL-7. We also observed that when porcine T cells were cultured with either human or mouse IL-7, these cells did not increase the survival or proliferation compared to negative controls. These results suggest that porcine T cells do not recognize human or mouse IL-7 as their survival factor.
Pyo Hong Ryull;Suh Chang Ok;Kim Gwi Eon;Rho Jae Kyung
Radiation Oncology Journal
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v.13
no.2
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pp.129-142
/
1995
Purpose: Traditionally the patients with early stage non-Hodgkin's lymphoma of the head and neck was treated with radiotherapy. But the results were not satisfactory due to distant relapse. Although combined treatment with radiotherapy and chemotherapy was tried with some improved results and chemotherapy alone was also tried in recent years, the choice of treatment for the patients with early stage non-Hodgkin's lymphoma of the head and neck has not been defined Therefore, in order to determine the optimum treatment method, we analysed retrospectively the outcomes of the patients with Ann Arbor stage I and II non-Hodgkin's lymphoma localized to the head and neck who were treated at Severance Hospital. Materials and Methods: 159 patients with stage I and II non-Hodgkin's lymphoma localized to the head and neck were treated at our hospital from January, 1979 to December, 1992. Of these patients, 114 patients whose primary sites were Waldeyer's ring or nodal region, and received prescribed radiation dose and/or more than 2 cycles of chemotherapy. were selected to analyze the outcomes according to the treatment methods ( radiotherapy alone, chemotherapy alone. and combined treatment with radiotherapy and chemotherapy ). Results: Five year overall actuarial survival of the patients whose Primary site was Waldeyer's ring was $62.5\%.$ and that of the Patients whose primary site was nodal region was $53.8\%$ There was no statistically significant difference between survivals of both groups. Initial response rate to radiotherapy. chemotherapy, and combined treatment was $92\%,\;83\%,\;94\%$ respectively, and 5 year relapse free survival was $49.9\%,\;52.4\%,\;58.5\%$ respectively ( statistically not significant ). In the patients with stage I. 3 year relapse free survival of chemotherapy alone group was $75\%$ and superior to other treatment groups. In the Patients with stage II, combined treatment group revealed the best result with $60.1\%$ of 3 year relapse free survival. The effect of sequential schedule of each treatment method in the Patients who were treated by combined modality was analyzed and the sequence of primary chemotherapy + radiotherapy + maintenance chemotherapy showed the best result ( 3 year relapse free survival was $79.1\%).$ There was no significant survival difference between BACOP regimen and CHOP regimen. Response to treatment was only one significant (p(0.005) prognostic factor on univariate analysis and age and mass size was marginally significant ( p(0.1). On multivariate analysis, age (p=0.026) and mass size (p=0.013) were significant prognostic factor for the relapse free survival. Conclusion: In summary, the patients who have non-Hodgkin's lymphoma of the head and neck with stage I and mass size smaller than 10 cm, can be treated by chemotherapy alone, but remainder should be treated by combined treatment method and the best combination schedule was the sequence of initial chemotherapy followed by radiotherapy and maintenance chemotherapy.
Background: Heat stress orchestrates neurodegenerative disorders and results in the formation of reactive oxygen species that leads to cell death. Although the immunomodulatory effects of ginseng are well studied, the mechanism by which ginseng alleviates heat stress in the brain remains elusive. Methods: Rats were exposed to intermittent heat stress for 6 months, and brain samples were examined to elucidate survival and antiinflammatory effect after Korean Red Ginseng (KRG) treatment. Results: Intermittent long-term heat stress (ILTHS) upregulated the expression of cyclooxygenase 2 and inducible nitric oxide synthase, increasing infiltration of inflammatory cells (hematoxylin and eosin staining) and the level of proinflammatory cytokines [tumor necrosis factor α, interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6], leading to cell death (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) and elevated markers of oxidative stress damage (myeloperoxidase and malondialdehyde), resulting in the downregulation of antiapoptotic markers (Bcl-2 and Bcl-xL) and expression of estrogen receptor beta and brain-derived neurotrophic factor, key factors in regulating neuronal cell survival. In contrast, KRG mitigated ILTHS-induced release of proinflammatory mediators, upregulated the mRNA level of the antiinflammatory cytokine IL-10, and increased myeloperoxidase and malondialdehyde levels. In addition, KRG significantly decreased the expression of the proapoptotic marker (Bax), did not affect caspase-3 expression, but increased the expression of antiapoptotic markers (Bcl-2 and Bcl-xL). Furthermore, KRG significantly activated the expression of both estrogen receptor beta and brain-derived neurotrophic factor. Conclusion: ILTHS induced oxidative stress responses and inflammatory molecules, which can lead to impaired neurogenesis and ultimately neuronal death, whereas, KRG, being the antioxidant, inhibited neuronal damage and increased cell viability.
Background: The prognostic value of microvessel density (MVD), reflecting angiogenesis, detected in ovarian cancer is currently controversial. Here we performed a meta-analysis of all relevant eligible studies. Materials and Methods: A comprehensive search of online PubMed, Medline, EMBASE and Sciencedirect was performed to identify all related articles. The search strategy was designed as 'microvessel density', 'ovarian cancer', 'ovarian neoplasm', 'CD34' and 'angiogenesis'. Results: The studies were categorized by author/year, number of patients, FIGO stage, histology, cutoff value for microvessel density, types of survival analysis, methods of hazard rations (HR) estimation, HR and its 95% confidence interval (CI). Combined hazard ratios suggested that high MVD was associated with poor overall survival (OS) and progression-free survival (PFS), with HR and 95% CIs of 1.84 (1.33-2.35) and 1.36 (1.06-1.66), respectively. Subgroup analysis showed that high MVD detected by CD34 was relevant for OS [HR=1.67 (1.36-2.35)], but not MVD detected with other antibodies [HR=2.11 (0.90-3.31)]. Another subgroup analysis indicated that high MVD in patients without pre-chemotherapy, but not with pre-chemotherapy, was associated with OS [HR=1.88(1.59-2.18 and HR=1.70 (-0.18-3.59)]. Conclusions: The OS and PFS with high MVD were significant poorer than with low MVD in ovarian cancer patients. However, high MVD detected by CD34 seems to be more associated with survival for patients without pre-chemotherapy.
Baghel, Kavita;Kazmi, Hasan Raza;Raj, Saloni;Chandra, Abhijit;Srivastava, Rajeshwar Nath
Asian Pacific Journal of Cancer Prevention
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v.15
no.1
/
pp.343-347
/
2014
Background: Maspin expression is a potential prognostic factor for various malignancies but its relation with gallbladder cancer is unknown and needs to be investigated needs to be investigated. We therefore here focused on maspin mRNA expression in normal, gall stone disease and gallbladder cancer subjects, with particular attention to prognostic importance in individuals with malignancies. Materials and Methods: This study was carried out at the Department of Surgical Gastroenterology, King George's Medical University, Lucknow, India. Gallbladder samples from normal (n=25), gall stone disease (n=25) and cancer patients (n=38) were analysed for maspin mRNA expression by semi-quantitative reverse transcriptase PCR and quantitative real time PCR. Statistical analysis was carried out using the Students t test or ANOVA. Survival analysis was conducted according to the Kaplan-Meier method and correlations were assessed using the Pearson correlation method. p<0.05 was considered statistically significant. Results: Significant increase (p=0.028) in expression of maspin mRNA was observed in gallbladder cancer as compared to gall stone disease, whereas no expression was found in normal tissues. Significant correlation (Pearson's coefficient(r)=-0.798, p<0.0001) was observed between relative quantification of maspin mRNA and survival of cancer patients after surgery, with significantly shorter (p=0.002) survival in patients having relative quantification >1.5 as compared to those having relative quantification <1.5. Similarly, significant differences in patient survival for maspin mRNA expression was observed for stage II (p=0.025) and III (p=0.011) cancer. Conclusions: Higher expression of maspin mRNA in gallbladder cancer has prognostic significance for stage II and III cancer, which needs to be investigated further.
Purpose: To investigate the relationship between MUC expression and clinicopathologic factors in advanced gastric cancer. Methods: A total of 237 tumor specimens were assessed for MUC expression by immunohistochemistry. The clinicopathologic factors were investigated with MUC1, MUC2, MUC5AC, and MUC6. Results: MUC1, MUC2, MUC5AC, and MUC6 expression was identified in 148 of 237 (62.4%), 141 of 237 (59.5%), 186 of 237 (78.5%), and 146 of 237 (61.6%) specimens, respectively. MUC1 expression was correlated with age, human epidermal growth factor receptor 2 (HER2) status, lymphatic invasion, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC1expression and lymphatic invasion, diffuse type of Lauren classification. MUC5AC expression was correlated with HER2 status, Lauren classification and histology. Further multivariate logistic regression analysis revealed a significant correlation between MUC5AC expression and HER2 status, diffuse and mixed type of Lauren classification. MUC2 and MUC6 expression were not correlated with clinicopathologic factors. The patients of MUC1 expression had poorer survival than those without MUC1 expression, but MUC2, MUC5AC or MUC6 were not related to survival. In an additional multivariate analysis that used the Cox proportional hazards model, MUC1 expression was not significantly correlated with patient survival independent of age, N-stage, and venous invasion. Conclusion: When each of these four MUCs expression is evaluated, in light of clinicopathologic factors, MUC1 expression may be considered as a prognostic factor in patients with advanced gastric cancer. Therefore, careful follow-up may be necessary because the prognosis is poor when MUC1 expression is present.
Kim Mi Sook;Yoo Seoung Yul;Cho Chul Koo;Yoo Hyung Joon;Kim Jae Young;Shim Jae Won;Lee Choon Taek;Kang Yoon Koo;Kim Tae You
Radiation Oncology Journal
/
v.15
no.3
/
pp.233-241
/
1997
Purpose : This study was done to evaluate the survival rate and Prognostic factors of patients with inoperable non-small cell lung cancer(NSCLC) treated with radiation therapy. Materials and Methods A retrospective analysis was undertaken of 62 Patients who had inoperable NSCLC treated with radiation therapy from January 1991 through December 1993. According to AJCC slaging, stage IIIA was 14 patients and stage IIIB was 48 patients. Forty Gy to 70.2Gy to the primary tumor site was delivered with daily fractions of 1.8Gy or 2Gy, 5days per week. Thirty-seven patients received neoadjuvant chemotherapy. Results : Complete, partial and no response to radiation therapy were 3 patients, 34 Patients and 25 patients, respectively The median survival period of all patients was 11 month. One rear survival rate, 2 year survival rateand 5 rear survival rate for all patients were 45.0%, 14.3%, and 6.0% respectively The median survival period was 6.5 months in stage IIIA and 13 months in stage IIIB. One year survival rates were 28.6% in stage IIIA and 50.3% in stage IIIB In univariaite analysis, prognostic factors affecting survival were T-s1aging, AJCC staging, and response after radiation therapy (P<0.05) . Pretreatment peformance status affected survival but was not statistically significant (0.05
0.1). In multivariate analysis, Pathology and response to radiation therapy are independently significant prognostic factor. T stage was marginally significant (P=0.0809). During follow-up duration, distant metastasis developed in 20 patients-bone metastasis in 10 patients, brain metastasis in 3 patients, liver mentastasis in 3 patients, contralateral lung metastasis in 1 patients and multiple metastases in 3 patients. Conclusion : Conventional radiotherapy alone or combined chemoradiotherapy are unlikely to achieve long term survival in patients with NSCLC. Surgery after concurrent chemoradiotherapy is Ivied to improve the local control in our hospital
Journal of The Korean Society of Clinical Toxicology
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v.5
no.1
/
pp.1-7
/
2007
Purpose: The aim of this study was to evaluate the characteristics and the prognostic factors of carbamate poisoned patients who visited emergency departments. Methods: From August 2005 to July 2006, we investigated the demographic feature, dose of exposure, time of exposure, alcohol intake, route of exposure, reason of exposure, site of exposure, pre-existing medical condition, time from exposure to emergency department (ED), transfer from other hospitals, vital sign at ED arrival, symptom or sign at ED arrival, and result of care of the patients who visited the ED of thirty-eight hospitals in Korea. According to the result of care, we divided the patients into two groups, the survival and the dead. To evaluated the prognostic factors, we calculated the odds ratio of each factor for the survival. Results: Among the sixty-eight patients, fifty-five patients (80.9%) were survival and thirteen patients (19.1%) were dead. The patients in the dead were older than the patients in the survival. The Glasgow coma scale (GCS) of the patients in the dead was lower than the GCS in the survival. The odds ratio of the GCS at ED arrival for the survival was 1.58 (95% CI; 1.23-2.05). Other factors showed no statistical significances. Conclusion: The GCS at emergency department arrival was the prognosis factor of the carbamate poisoned patients who visited emergency departments. If the carbamate poisoned patients showed altered mentalities, they should be provided intensive care, immediately.
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