• Molecules and Cells
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• v.28 no.2
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• pp.99-103
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• 2009

Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of several human diseases as multi-copy members in the human genome. Their gene expression profiling could provide us with important insights into the pathogenic relationship between HERVs and cancer. In this study, we have evaluated the genomic structure and quantitatively determined the expression patterns in the env gene of a variety of HERV family members located on six specific loci by the RetroTector 10 program, as well as real-time RT-PCR amplification. The env gene transcripts evidenced significant differences in the human tumor/normal adjacent tissues (colon, liver, uterus, lung and testis). As compared to the adjacent normal tissues, high levels of expression were noted in testis tumor tissues for HERV-K, in liver and lung tumor tissues for HERV-R, in liver, lung, and testis tumor tissues for HERV-H, and in colon and liver tumor tissues for HERV-P. These data warrant further studies with larger groups of patients to develop biomarkers for specific human cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2319-2324
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• 2012

Aim: To investigate the expression of three components of the Hedgehog (Hh) signaling pathway (SHH, SMO and GLI1) in human colorectal cancer (CRC) tissues and evaluate their association with clinicopathologic characteristics of the patients. Methods: Fresh tumor tissues and matched tissues adjacent to the tumor were collected from 43 CRC patients undergoing surgery. Normal colorectal tissues from 20 non-CRC cases were also sampled as normal controls. The expression of SHH, SMO, GLI1 mRNAs was assessed by RT-PCR and proteins were detected by immunohistochemical staining. Associations with clinicopathological characteristics of patients were analyzed. Results: SHH mRNA was expressed more frequently in tumor tissues than in normal tissues, but the difference did not reach significance in comparison to that in the adjacent tissues. SMO and GLI1 mRNAs were expressed more frequently in tumor tissues than in both adjacent andnormal tissues. The expression intensities of SHH, SMO, GLI1 mRNA in tumor tissues were significantly higher than those in adjacent tissues and normal tissues. Proteins were also detected more frequently in tumors than other tissues. No significant links were apparent with gender, age, location, degree of infiltration or Dukes stage. Conclusion: Positive rates and intensities of mRNA and protein expression of Hh signaling pathway related genes SHH, SMO, GLI1 were found to be significantly increased in CRC tissues. However, over-expression did not appear to be associated with particular clinicopathological characteristics.

• Korean Journal of Microbiology
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• v.4 no.2
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• pp.5-10
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• 1966

The relationships between tumor score and peroxidase activities of tomato stems infected with Agrobacterium tumefaciens strain A6Kl, B6, T372 11BNV6, 11BV7 and wounded stem as a control were examined in relation to crown gall tumor development on purpose to study the lignification of tumor tissue which is affected to the development of crown gall tumor. As the previous paper has been mentioned the fact that the induction of tumor tissues were inhibited or limited in the lignified stem of host plant. It was presumed that the activities of peroxidase related to the development of lignification were decreased during the period of tumor development. But the experimental result in this experiment shows that the peroxidase activities of crown gall tumor-tissues infected with the A. tumefaciens strains which are already known as virulent are increasing during four weeks, however, in the strain 11BNV6 and wound the peroxidase activities are decreasing on the second week after the inoculation of the bacteria strains. These results could be explained on the basis of that possible regulatory agents of lignification which were accumulated in tumor tissues, IAA, ascorbic acid, glutathion(GSH) and caffeic acid esters, were postulated to act as antioxidants which has been suggested by Stafford. Total nitrogen contents in relation to crown gall tumor development were determined for the detection of protein synthesis related to the enzyme activities which are increasing in the time of plant growth. Generally six groups are contained the largest amount of nitrogen on the second week after the inoculation of the bacterium. Comparing to the tumor score, it is presumed that the all of enzyme activities including peroxidase in tumor tissues are increasing from the second week through the third week after the inoculation of bacterium and the protein synthesis is stimulated under the most appropriated temperature during the above periods.

• Genomics & Informatics
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• v.16 no.2
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• pp.30-35
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• 2018

Patient-derived xenograft (PDX) models are useful tools for tumor biology research and testing the efficacy of candidate anticancer drugs targeting the druggable mutations identified in tumor tissue. However, it is still unknown how much of the genetic alterations identified in primary tumors are consistently detected in tumor tissues in the PDX model. In this study, we analyzed the genetic alterations of three primary colorectal cancers (CRCs) and matched xenograft tissues in PDX models using a next-generation sequencing cancer panel. Of the 17 somatic mutations identified from the three CRCs, 14 (82.4%) were consistently identified in both primary and xenograft tumors. The other three mutations identified in the primary tumor were not detected in the xenograft tumor tissue. There was no newly identified mutation in the xenograft tumor tissues. In addition to the somatic mutations, the copy number alteration profiles were also largely consistent between the primary tumor and xenograft tissue. All of these data suggest that the PDX tumor model preserves the majority of the key mutations detected in the primary tumor site. This study provides evidence that the PDX model is useful for testing targeted therapies in the clinical field and research on precision medicine.

• BMB Reports
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• v.41 no.9
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• pp.626-634
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• 2008

Novel cancer biomarkers are required to achieve early diagnosis and optimized therapy for individual patients. Cancer is a disease of the genome, and tumor tissues are a rich source of cancer biomarkers as they contain the functional translation of the genome, namely the proteome. Investigation of the tumor tissue proteome allows the identification of proteomic signatures corresponding to clinico-pathological parameters, and individual proteins in such signatures will be good biomarker candidates. Tumor tissues are also a rich source for plasma biomarkers, because proteins released from tumor tissues may be more cancer specific than those from non-tumor cells. Two-dimensional difference gel electrophoresis (2D-DIGE) with novel ultra high sensitive fluorescent dyes (CyDye DIGE Fluor satulation dye) enables the efficient protein expression profiling of laser-microdissected tissue samples. The combined use of laser microdissection allows accurate proteomic profiling of specific cells in tumor tissues. To develop clinical applications using the identified biomarkers, collaboration between research scientists, clinicians and diagnostic companies is essential, particularly in the early phases of the biomarker development projects. The proteomics modalities currently available have the potential to lead to the development of clinical applications, and channeling the wealth of produced information towards concrete and specific clinical purposes is urgent.

• The Korean Journal of Physiology
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• v.2 no.1
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• pp.23-30
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• 1968

Tissue homogenates of 12 kinds of human cancer tissues were incubated separately in medium containing $C^{14}-1-glucose$ and $C^{14}-6-glucose$ as a substrate in order to observe the oxidative pathway of glucose in the tumor tissues. At the end of 3 hours incubation in the Dubnuff metabolic shaking incubator, respiratory $CO_2$ samples trapped by alkaling which was placed in the center well of incubation flask were analysed for total $CO_2$ production rates and their radioactivities. The tissue homogenate samples after incubation were analyzed for their concentrations of glucose, lactate and pyruvate. Calculations were made on the glucose consumption rate and accumulation rates of lactate and pyruvate. Fractionation of oxidative pathway of glucose was carried out by calculating $C^{14}O_2 yields from C-1 and C-6 carbon of glucose. The following results were obtained. 1. In 12 kinds of human cancer, total $CO_2$ production rates were less than $8{\mu}M/gm$ except 2 cases. These lower values impressed that oxidative metabolism in the tumor tissues generally inhibited as compared with that in normal tissues. On the other hand, fractions of $CO_2$ derived from glucose to total $CO_2$ production rates (RSA) were less than 10% in every case. These facts showed that oxidation of glucose into $CO_2$ was remarkably inhibited in the tumor tissues. 2. Factions of glucose disappeared into $CO_2\;(RGD_{CO_2})$, lactate $(RGD_L)$, pyruvate $(RGD_P)$ to glucose consumption rates were as follows. $RGD_{CO_2}$ were less than 2% in cases of in this experiment and $RGD_L$ showed more than 5% except in 2 cases. These facts showed that anaerobic degradation of glucose into 3 carbon compounds was easily proceeded but further degradation into $CO_2$ via the TCA cycle was greatly inhibited resulting in accumulation of lactate. There are large variation in values of $RGD_P$ in different kinds of tumor tissue but relatively higher values in $RGD_{CO_2}$ were obtained in the tumor tissues as compared with those of normal tissues. 3. The oxidative pathway of glucose in tumor tissues were analyzed from the values of RSA which were obtained in $C^{14}-1\;and\;C^{14}-6-glucose$ incubation experiments. It was found that 3% of $CO_2$ derived from glucose were oxidized via the principal EMP-TCA cycle and the remainder were via alternate pathway such as HMP in the liver cancer and values in other cancer tissues were as follows; 4% in the tongue cancer, 6% in the colon cancer, 6% in the lung cancer, 9% in the stomach cancer, 11% in the ovarian cancer, 12% in the neck tumor, 22% in the uterine cancer, 22% in the bladder tumor, 32% in the spindle cell sarcoma and 65% in the brain tumor. These values except later 2 cases showed less than 30% which is the lowest value among the normal tissues. Even in the brain tumor in which showed highest value in the tumor group. It is reasonable to suppose that this fraction was remarkably decreased because values in normal brain tissue was more than 90%. From the above data, it was concluded that in tumor tissues, oxidation of glucose via TCA cycle was greatly inhibited but correlation between degree of inhibited oxidation of glucose via TCA cycle and malignancy of tumor were not clarified in this experiments.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2559-2563
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• 2014

Purpose: We investigated the expression of epithelial $Ca^{2+}$ channel transient receptor potential vanilloid (TRPV) 5 and 6 in non-small-cell lung cancer (NSCLC) and assessed their prognostic role in patients after surgical resection. Materials and Methods: From January 2008 to January 2009, 145 patients who had undergone surgical resection of NSCLCs were enrolled in the study. Patient clinical characteristics were retrospectively reviewed. Fresh tumor samples as well as peritumor tissues were analyzed for TRPV5/6 expression using immune-histochemistry (IHC) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Patients were grouped based on their TRPV5 and TRPV6 levels in the tumor tissues, followed up after surgery, and statistically analyzed to examine the prognostic roles of TRPV5 and TRPV6 on patients' survival after surgical resection of NSCLCs. Results: Using IHC, among the 145 patients who had undergone surgical resection of NSCLCs, strong protein expression (grade${\geq}2$) of TRPV5 and TRPV6 was observed in a lower percentage of primary tumor tissues than in non-tumor tissues of same patients. Similar findigns were obtained with the RT-PCR test for mRNA levels. Decreased overall mRNA levels of TRPV5 and TRPV6 were associated with a worse overall survival rate (p=0.004 and p=0.003 respectively) and shorter recurrence-free survival (p<0.001 and p<0.001 respectively). The combining effect of TRPV5 and TRPV6 on survival was further investigated using multivariate analysis. The results showed that a combination of low expression of TRPV5 and TRPV6 could be an independent predictor of poor recurrence-free survival (p=0.002). Conclusions: Decreased expression of TRPV5/6 in tumor tissues was observed in NSCLC patients and was associated with shorter median survival time after surgical resection. Combined expression of TRPV5 and TRPV6 in tumor tissues demonstrated promising prognostic value in NSCLC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4951-4956
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• 2014

Purpose: To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes. Methods: IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis. Results: IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (III and IV, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (III and IV, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2-tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189). Conclusion: Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2459-2463
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• 2015

Background: To investigate the expression and clinical significance of zinc finger protein 217 (ZNF217) in human colorectal carcinoma (CRC). Materials and Methods: The expression of ZNF217 in 60 CRC tissues and matched tumor adjacent tissues, collected between January 2013 and June 2014, was assessed immunohistochemically. The relationship between the expression of ZNF217 and clinicopathlogical features was analyzed by Pearson chi-square test. In addition, siRNA was used to down-regulate the expression of ZNF217 in CRC cells. The effects of ZNF217 for cell migration and invasion were measured by wound healing assay and transwell assay, respectively. Results: The expression level of ZNF217 was significantly higher in CRC tissues than in tumor adjacent tissues (p<0.05), positively correlating with tumor size, lymphatic metastasis and advanced TNM stage (p<0.05). Down-regulation of ZNF217 in CRC cells could significantly suppress cell migration and invasion. Conclusions: ZNF217 is overexpressed in colorectal carcinoma tissues and is associated with tumor malignant clinicopathological features. ZNF217 may promote CRC progression by inducing cell migration and invasion.

• Journal of Plant Biology
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• v.29 no.4
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• pp.275-283
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• 1986

Inoculation of carrot discs with Agrobacterium rhizogenes harboring Ri plasmid resulted in transformation of cells, as revealed by the tumors and hairy roots arising from them. Measurements of IAA content using HPLC indicate that it is higher in tumors and inoculated tissues than in uninoculated tissue. A lot of meristemoids and vessel elements formed I tumor tissue and the hairy roots differentiated from meristemoids. IAA content in tumor tissues is decreased with hairy root and vessel elements formation from them. Formation of wound callus in uninoculated tissues resulted on wound healing but no formation of vessel elements and hairy roots. Tumor tissues show continuous growing on hormone free medium.