Biomedical subjects

Hyun Cheol Chung

Publications and source records attributed to Hyun Cheol Chung.

At least 19 recordsLinked to original sources

PubMed2006

A phase II trial of weekly fractionated irinotecan and cisplatin for advanced gastric cancer.

PURPOSE: This study was to evaluate the activity and the safety of a combination chemotherapy regimen of weekly fractionated irinotecan and cisplatin in advanced gastric cancer patients. METHODS: Patients with advanced gastric adenocarcinoma with either chemotherapy-naive or only one prior chemotherapy regimen received irinotecan 50 mg/m2 followed by cisplatin 30 mg/m2. Both drugs were administered weekly for 3 consecutive weeks, followed by 1-week rest. Treatment was repeated until disease progression occurred. Response evaluation was performed according to the RECIST criteria. RESULTS: Forty-seven patients (13 chemo-naive, 34 prior chemotherapy) were enrolled. Of 46 evaluable patients, overall response rate was 25.5% (95% CI, 12.9-39.3%) and disease control rate was 63.8% (95% CI, 50.9-79.5%) by intent-to-treat analysis. The time to progression and overall survival duration were 21 and 44 weeks, respectively. One-year survival rate was 41.6%. The most frequent grade 4 toxicity was neutropenia, which was the major cause of treatment delay. Non-hematological toxicities of grade 3-4 were rare with occurrence rate of 14.9% for anorexia and emesis. CONCLUSIONS: Fractionated irinotecan combined with cisplatin with 3-week-on and 1-week-off schedule produced favorable clinical results for advanced gastric cancer. Because of the feasible efficacy and low non-hematologic toxicity, this treatment could be a promising salvage regimen in patients who have failed to taxanes.

Adenocarcinoma↗

PubMed2006

Severe hypothyroidism induced by thyroid metastasis of colon adenocarcinoma: a case report and review of the literature.

An 85-year-old man who had undergone a right hemicolectomy for colon cancer presented with severe hypothyroidism and hoarseness 21 months after the operation. The serum thyrotropin (TSH) was markedly elevated to 118.14 microIU/mL and serum free thyroxine (fT4) level was markedly suppressed to 0.34 ng/dL. Symptoms of hoarseness and neck swelling were already evident 4 months prior at which time tests for normal thyroid function were performed. The patient was referred due to aggravated pain on his diffusely enlarged hard goiter. An enlarged thyroid with some calcification was noticed in the neck ultrasonography with multiple cervical lymphadenopathies. Core biopsy of the thyroid gland showed invasion of poorly differentiated adenocarcinoma cells. Immunohistochemical studies showed positive staining only for carcinoembryonic antigen (CEA). There were multiple lung parenchymal nodules and adrenal masses at the time of evaluation. The patient was started on palliative chemotherapy with thyroid hormone replacement and gradually became euthyroid. From these findings and the clinical observations, thyroid metastasis with hypothyroidism developing acutely from metastatic colon adenocarcinoma was diagnosed.

Adenocarcinoma↗

PubMed2006

A phase II study of infusional 5-fluorouracil and low-dose leucovorin with docetaxel for advanced gastric cancer.

BACKGROUND: The standard chemotherapy regimen for advanced gastric cancer has not yet been established. We investigated the efficacy and the safety of the combination of docetaxel with infusional 5-fluorouracil (5-FU) and leucovorin (FLT) in advanced gastric cancer. METHODS: Patients received docetaxel 75 mg/m(2) (1-hour infusion) followed by a leucovorin bolus 20 mg/m(2) and a 24-hour infusion of 5-FU 1,000 mg/m(2) (day 1-3) every 3 weeks. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and the toxicity was evaluated by National Cancer Institute common toxicity criteria (NCI-CTC). RESULTS: Sixty-six patients were enrolled. Median relative dose intensity was 86%. Of 57 evaluable patients, the overall response rate was 25.7%. The response rate was 34.2% in chemonaïve patients and 14.2% in the patients who had previously received treatment. Median time to progression and overall survival duration were 5.2 and 9.7 months, respectively. The most frequent grade 3-4 toxicity was neutropenia, which was the major cause of treatment delay. Other hematological and nonhematological toxicities were rare. CONCLUSIONS: The FLT regimen showed a comparable efficacy with other second-generation regimens. Because of the low nonhematological toxicity, this could be a potential alternative to the cisplatin-containing regimens in gastric cancer.

Adenocarcinoma↗

PubMed2006

Intermediate dose 5-fluorouracil-induced encephalopathy.

As an acute neurotoxicity, high dose 5-fluorouracil (5-FU)-induced encephalopathy is well-known, but encephalopathy associated with lower dose is rarely reported. Here, we report a case of a male with anal cancer who was treated with 5-FU 1000 mg/m(2), continuous infusion for 5 days q4 weeks. At the second and the fourth cycles of chemotherapy, sudden confusion, cognitive dysfunction and disorientation occurred during 5-FU infusion. They were accompanied by hyperammonemia in the absence of focal neurological deficits or structural abnormalities. These symptoms completely disappeared and the serum ammonia level returned to normal after discontinuation of 5-FU and conservative care. In order to investigate a possible deficit of dihydropyrimidine dehydrogenase (DPD), we checked its mRNA level before and after treatment using real-time PCR. The patient's pre-treatment level was 80% compared with reference group, and it was elevated up to 187% of initial after 5-FU treatment, implying that that his encephalopathy may be 5-FU catabolite type rather than DPD deficiency. In conclusion, we report that encephalopathy can develop even with the dose of 5-FU lower than ever reported, and it should be considered as a differential diagnosis for proper management.

Aged↗

PubMed2006

Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines.

OBJECTIVES: Significant variability in the efficacy and toxicity of an anticancer drug is observed in cancer patients. Currently, there are no standard tools for prediction of a patient's tumor response or his risk of adverse events to chemotherapy. METHODS: We investigate an association between polymorphisms of gemcitabine metabolism-related genes and its chemosensitivity in vitro using 62 human cancer cell lines of various origins. Polymorphisms of gemcitabine metabolism-related genes of deoxycytidine monophosphate deaminase (DCTD), deoxycytidine kinase (DCK) and ribonucleotide reductase M1 (RRM1) were evaluated using the CEQ8000 Genetic analysis system and GeneDoc software. Chemosensitivity of gemcitabine was expressed as an IC50 using MTT assay. RESULTS: The frequency of the polymorphisms was 21% in DCTD 315T>C, 45.2% in RRM1 1082C>A, 59.7% in RRM1 2455A>G, and 79% in RRM1 2464G>A. When examining the association between these polymorphisms and IC50, only the RRM1 2464G>A showed the tendency to be more chemosensitive to gemcitabine (P=0.011), and haplotypes containing 2464G>A polymorphism also showed the association with chemosensitivity when compared to wild-type RRM1 (G2464G). We could not see the significant differences of mRNA expression level with real-time PCR between cell lines according to G2464A polymorphism. In oligonucleotide microarray 73 GenBank Accession Number (69 genes) were selected which expressed differently between RRM1 wild-type and the G2464A polymorphism. CONCLUSIONS: RRM1 2464G>A polymorphism demonstrated an association with gemcitabine sensitivity, which needs functional studies with co-expressing genes and prospective clinical studies for the clinical application as a predictive bio-marker.

Antimetabolites, Antineoplastic↗

PubMed2006

Systematic analysis of cDNA microarray-based CGH.

cDNA microarray-based CGH (Microarray-CGH) is a useful technique for detecting genomic aberrations with a high resolution. However, the criteria for determining a genomic alteration have not been determined. We evaluated the genome-wide measurement of copy number of each gene in normal gastric and placenta tissues with both sex-matched, direct and sex-mismatched, indirect designs using 17K cDNA microarray. The results revealed the range of genomic copy number of normal tissues to be +/-0.3 of the log(2) ratio (gain >0.3, loss <-0.3) in the autosomal genes with direct and indirect designs. The copy number at a gene level from the X chromosomal genes using the direct and indirect sex-mismatched designs was +/-0.68 of the log(2) ratio (amplification >0.68, deletion <-0.68). In summary, the suggested method can be used as a guideline for analysis of genomic aberration using a Microarray-CGH in both direct and indirect designs.

Chromosomes, Human↗

PubMed2005

A pilot study of trans-arterial injection of 166Holmium-Chitosan complex for treatment of small hepatocellular carcinoma.

Percutaneous approaches, such as percutaneous ethanol injection and radiofrequency ablation, have been most widely used for hepatocellular carcinoma patients who were not eligible for surgery. New technologies to improve the efficacy are currently needed. (166)Holmium is a neutron activated radionuclide, and has several beneficial radiophysical characteristics for internal radiation therapy. (166)Holmium-Chitosan complex, in which chitosan is chelated with (166)Holmium, was developed as a radiopharmaceutical for cancer therapy. We have conducted a pilot study to evaluate the clinical efficacy of transarterial administration of (166)Holmium-Chitosan complex in patients with a single and small (< 3 cm) hepatocellular carcinoma. (166)Holmium-Chitosan complex, at a dose of 20 mCi per cm of tumor mass-diameter, was administered through the artery that directly fed the tumor. Twelve patients were treated with a median follow-up duration of 26 (range: 12-61) months. The tumor diameter ranged between 1.5 and 2.5 cm. Ten patients (83%) had complete response and two (17%) had partial response. The median complete response duration was not reached. The median AFP level declined from 83.8 to 8.3 ng/mL within 2 months after treatment. No grade III/IV toxicity was observed. Grade I and II toxicities were observed in four patients (2 abdominal pain, 1 fever, and 1 AST/ALT elevation). No toxic death occurred. This preliminary study shows a promising and durable complete response rate with an acceptable safety profile. Further studies with greater accrual of patients are warranted.

Adult↗

PubMed2005

Attenuation of telomerase activity by hammerhead ribozyme targeting human telomerase RNA induces growth retardation and apoptosis in human breast tumor cells.

Ribozyme possesses specific endoribonuclease activity and catalyzes the hydrolysis of specific phosphodiester bonds, which results in the cleavage of target RNA sequences. Here, we evaluated the ability of hammerhead ribozymes targeting human telomerase RNA (hTR) to inhibit the catalytic activity of telomerase and the proliferation of cancer cells. Hammerhead ribozymes were designed against 7 NUX sequences located in open loops of the hTR secondary structure. We verified the ribozyme specificity by in vitro cleavage assay by using a synthetic RNA substrate. Subsequently, we introduced ribozyme expression vector into human breast tumor MCF-7 cells and assessed the biologic effects of ribozyme. Hammerhead ribozyme R1 targeting the template region of hTR efficiently cleaved hTR in vitro, and stable transfectants of this ribozyme induced the degradation of target hTR RNA and attenuated telomerase activity in MCF-7 cells. Moreover, the ribozyme R1 transfectant displayed a significant telomere shortening and a lower proliferation rate than parental cells. Clones with reduced proliferation capacity showed enlarged senescence-like shapes or highly differentiated dendritic morphologies of apoptosis. In conclusion, the inhibition of telomerase activity by hammerhead ribozyme targeting the template region of the hTR presents a promising strategy for inhibiting the growth of human breast cancer cells.

Apoptosis↗

PubMed2005

Gene copy number change events at chromosome 20 and their association with recurrence in gastric cancer patients.

PURPOSE: This study examined the gene copy number change events at chromosome 20 in gastric cancer, and their possible relationship with recurrence using cDNA microarray-based comparative genomic hybridization. EXPERIMENTAL DESIGN: Thirty pairs of gastric tumor and normal gastric tissues were used in the cDNA microarray-based comparative genomic hybridization. The cDNA microarrays containing 17,000 sequence-verified human gene probes were used in a direct comparison design, where genomic DNAs from the normal and tumor tissues were labeled with fluorescent dyes Cy3 and Cy5, respectively, and cohybridized. Genes with log(2) (Cy5/Cy3) > or = 0.58 in at least one case were selected as the amplified genes. In order to search for the association between gene copy number changes and the recurrence status, patients were grouped according to their recurrence status. Gene selection between the two groups was done, and each patient was given a score based on the sum of the selected genes' ratios. Logistic regression analysis was carried out in order to determine if the score of a group of patients was correlated with a recurrence. RESULTS: A group of genes including NCOA6, CYP24A1, PTPN1, and ZNF217 was amplified in gastric cancer. Another group of 39 genes, whose sum of copy number change levels was significantly associated with a poor prognosis for recurrence, was selected (P < 0.05). CONCLUSION: Ninety-six amplified genes at chromosome 20 of gastric cancer are reported. A scoring system based on gene copy changes at chromosome 20 can provide an independent patient grouping system that can distinguish patient recurrence status and survival.

Aged↗

PubMed2005

Determination of genes related to gastrointestinal tract origin cancer cells using a cDNA microarray.

PURPOSE: We evaluated the genome-wide gene expression profiles of various cancer cell lines to identify the gastrointestinal tract cancer cell-related genes. EXPERIMENTAL DESIGN: Gene expression profilings of 27 cancer cell lines and 9 tissues using 7.5K human cDNA microarrays in indirect design with Yonsei reference RNA composed of 11 cancer cell line RNAs were done. The significant genes were selected using significant analysis of microarray in various sets of data. The selected genes were validated using real-time PCR analysis. RESULTS: After intensity-dependent, within-print-tip normalization by loess method, we observed that expression patterns of cell lines and tissues were substantially different, divided in two discrete clusters. Next, we selected 115 genes that discriminate gastrointestinal cancer cell lines from others using significant analysis of microarray. Among the expression profiles of five gastric cancer cell lines, 66 genes were identified as differentially expressed genes related to metastatic phenotype. YCC-16, which was established from the peripheral blood of one advanced gastric cancer patient, produced a unique gene expression pattern resembling the profiles of lymphoid cell lines. Quantitative real-time reverse transcription-PCR results of selected genes, including PXN, KRT8, and ITGB5, were correlated to microarray data and successfully discriminate the gastrointestinal tract cancer cell lines from hematologic malignant cell lines. CONCLUSIONS: A gene expression database could serve as a useful source for the further investigation of cancer biology using the cell lines.

Cell Line, Tumor↗

PubMed2005

Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer.

PURPOSES: We evaluated the efficacy and tolerability of gemcitabine monotherapy in heavily pretreated, breast cancer patients as salvage chemotherapy. METHODS: A weekly infusion of gemcitabine at 850 mg/m2 for 30 min, for 3 of every 4 weeks, was introduced in advanced breast cancer patients who had failed previous doxorubicin and taxane based chemotherapy. There was no dose modification, and the treatment was delayed until the leukopenia was recovered with G-CSF support. The efficacy was evaluated every three cycles and the treatment was continued until either disease progression or 12 cycles. RESULTS: Of 41 enrolled patients, 38 were evaluable with a median age of 47. Total 178 cycles of gemcitabine was administered and the relative dose intensity was 89. The toxicity was mild with 12 of grade III neutropenia and 14 of grade III/IV thrombocytopenia without clinical symptoms. The response rate was 20 (8/38), comprising two complete and six partial responses. The median response duration and overall survival were 9 (2-25) and 11 months, respectively. The overall survival of 12 months was better in the third line patients than the 7 months in the fourth line treatment group. CONCLUSION: Gemcitabine monotherapy is effective and safe as salvage treatment in heavily pretreated, breast cancer patients.

Adult↗

PubMed2005

Cyclic induction of senescence with intermittent AZT treatment accelerates both apoptosis and telomere loss.

BACKGROUND: 3'-azido-2',3'-dideoxythymidine (AZT) is phosphorylated intracellularly to 3'-azido-3'-deoxythymidine-5'-triphosphate (AZT-TP), which is incorporated into telomeric DNA, thereby blocking chain elongation. AZT is also known to inhibit reverse transcriptase, as well as other cellular enzymes including DNA polymerase gamma, thymidine kinase, and telomerase. METHODS: We induced cancer cell senescence by treating MCF-7 cells with AZT in dosages of IC10 and IC20 for an extended period (about 120 population doublings (PD)). We then investigated the sequential changes in cellular growth, expression of telomerase subunits and transcription factors (c-Myc, Mad1), telomerase activity and telomere length. RESULTS: Senescence, apoptosis, growth delay, inhibition of telomerase activity and shortening of telomere length were all observed in a dose- and time-dependent manner. After the onset of senescence, the apoptosis rate increased slowly during early PDs. In contrast to senescence, the apoptotic rate showed little change after AZT removal, while it increased suddenly and significantly in a dose-dependent manner upon the second introduction of AZT. Continuous shortening of the telomeric length was observed with AZT, and, upon re-exposure to AZT, shortening of the telomere occurred more rapidly than with first exposure. Of the telomerase subunits, telomerase reverse transcriptase (hTERT) and c-Myc were the first to show a reduction in activity after AZT treatment, followed by changes in hTER , Mad1 and hTEP-1. CONCLUSION: Cyclic treatment with AZT initially suppressed hTERT and c-Myc, followed by suppression of hTER, Mad1 and hTEP-1. Furthermore, the treatment accelerated both telomere loss and apoptosis, even when administered at a senescence-inducing dosage level.

Apoptosis↗

PubMed2005

Quantitative detection of telomerase activity by real-time TRAP assay in the body fluids of cancer patients.

Real-time TRAP assay was developed to improve the sensitivity and quantitative detection of telomerase activity in the body fluids of cancer patients. The sensitivity and clinical significance of the real-time TRAP assay was investigated. Real-time PCR protocol was modified by using ACX primer and SYBR green mixture from the process of TS primer extension. Real-time TRAP showed high correlation (r2=0.843, p=0.001) and sensitivity (25 times higher) compared to conventional TRAP. Of 164 samples, there were 8 positives in cytology (4.9%), 7 (4.3%) using the conventional TRAP, and 41 (25%) using real-time TRAP. In cytology positive samples, real-time TRAP showed a higher positivity than conventional TRAP (75% vs 63%) suggesting a higher sensitivity in the body fluids. There was a tendency towards a longer progression-free duration in telomerase negative patients than in positive patients, as determined by conventional and real-time TRAP. The diagnostic interval between the first positivity documentation and clinical progression was short in the order of real-time TRAP, conventional TRAP and cytology. In conclusion, real-time TRAP assay can detect telomerase activity at an earlier phase of cancer progression and can replace conventional TRAP assay for detecting the telomerase activity in body fluids.

Body Fluids↗

PubMed2004

Growth inhibitory effects of trastuzumab and chemotherapeutic drugs in gastric cancer cell lines.

The various treatments for advanced gastric cancer have limitations and induce only marginal survival benefit. HER-2/neu protein is overexpressed in several types of human cancers and its amplification is associated with poor prognosis. Recombinant humanized anti-HER-2/neu antibody (trastuzumab) not only inhibits the proliferation of HER-2/neu overexpressing tumor cells but also augments the cytotoxicity of concomitant chemotherapeutic agents in metastatic breast cancer. In this study, we evaluated the growth inhibitory effects of trastuzumab in gastric cancer cells. HER-2/neu protein was evaluated by immunohistochemical analysis in seven gastric cancer cell lines. MTT assay was performed to evaluate the growth inhibitory effects of trastuzumab and three chemotherapeutic agents, doxorubicin, cisplatin and paclitaxel, both alone and in combinations. The changes of cell cycle after trastuzumab treatment were analyzed by flow cytometry. Four of the cell lines, YCC-2 with strong positivity of HER-2/neu expression, NCI-N87 with moderate positivity, YCC-3 with weak positivity, and SK-BR-3 as a positive control, were selected. After in vitro MTT assay for 1-day and 5 consecutive days' treatment of trastuzumab at various concentrations, growth inhibition was not observed in any cancer cell lines. However, there was variable dose-dependent sensitivity to doxorubicin, cisplatin and paclitaxel. YCC-2 and SK-BR-3 cancer cells were more sensitive to three chemotherapeutic drugs, constantly (P<0.05). The combination of 5 consecutive days' treatment of trastuzumab with 1-day doxorubicin treatment showed significant growth inhibition only in YCC-2 and NCI-N87 gastric cancer cells. After 1-day trastuzumab treatment, the S-phase fraction was decreased by 52 and 70% in YCC-2 and SK-BR-3, respectively. In conclusion, the expressions of HER-2/neu protein in gastric cancer cells are variable, and concomitant treatments of trastuzumab with doxorubicin increase cytotoxicity. This suggests that trastuzumab-based biologic therapy with chemotherapeutic agents can be applied in gastric cancer treatment.

Antibiotics, Antineoplastic↗

PubMed2004

Statistical methods of translating microarray data into clinically relevant diagnostic information in colorectal cancer.

MOTIVATION: It is a common practice in cancer microarray experiments that a normal tissue is collected from the same individual from whom the tumor tissue was taken. The indirect design is usually adopted for the experiment that uses a common reference RNA hybridized both to normal and tumor tissues. However, it is often the case that the test material is not large enough for the experimenter to extract enough RNA to conduct the microarray experiment. Hence, collecting n cases does not necessarily end up with a matched pair sample of size n. Instead we usually have a matched pair sample of size n1, and two independent samples of sizes n2 and n3, respectively, for 'reference versus normal tissue only' and 'reference versus tumor tissue only' hybridizations (n=n1 + n2 + n3). Standard statistical methods need to be modified and new statistical procedures are developed for analyzing this mixed dataset. RESULTS: We propose a new test statistic, t3, as a means of combining all the information in the mixed dataset for detecting differentially expressed (DE) genes between normal and tumor tissues. We employed the extended receiver operating characteristic approach to the mixed dataset. We devised a measure of disagreement between a RT-PCR experiment and a microarray experiment. Hotelling's T2 statistic is employed to detect a set of DE genes and its prediction rate is compared with the prediction rate of a univariate procedure. We observe that Hotelling's T2 statistic detects DE genes more efficiently than a univariate procedure and that further research is warranted on the formal test procedure using Hotelling's T2 statistic. CONTACT: bskim@yonsei.ac.kr.

Adult↗

PubMed2004

Coordination modes vs. antitumor activity: synthesis and antitumor activity of novel platinum(II) complexes of N-substituted amino dicarboxylic acids.

The trans-(+/-)-1,2-diaminocyclohexaneplatinum(II) complexes of multidentate L-glutamate (Glu) and L-aspartate (Asp) were prepared and their antitumor activity was examined in relation with their coordination modes. All these complexes were obtained as a mixture of (O,O')- and (O,N)-chelate isomers due to rapid isomerization of the initially formed (O,O')-isomer to the thermodynamically more stable (O,N)-isomer. The (O,O')/(O,N)-isomeric mixture with the mole ratio of 80/20 exhibited excellent antitumor activity while the pure (O,N)-isomer was only marginally active. Therefore, in order to prevent the linkage isomerization of the active (O,O')-isomer to the inactive (O,N)-isomer, we have designed N-substituted amino dicarboxylic acids as a leaving group and prepared a new series of complexes, [Pt(dach)(RGlu)] and [Pt(dach)(RAsp)] (dach=trans-(+/-)-1,2-diaminocyclohexane; R=acetyl (Ac), propionyl (Pro), pivaloyl (Piv), carbobenzyloxy (Cbz) or phthaloyl (Phth)) and characterized by means of elemental analyses, and 1H NMR, 195Pt NMR and IR spectroscopies. The N-substituted amino dicarboxylate ligands were found to coordinate to platinum(II) ion through only the (O,O')-chelation mode, and their Pt(II) complexes were chemically stable in aqueous solution. The present Pt(II) complexes of N-substituted amino dicarboxylic acids showed excellent antitumor activity against both murine leukemia L1210 and human tumor cells. Especially, the highly hydrophobic N-phthaloylglutamate complex, [Pt(dach)(PhthGlu)], exhibited an outstanding in vitro activity (IC50=2.22 microM) on the human stomach cancer cells which are not responsive to cisplatin and carboplatin.

Amino Acids, Dicarboxylic↗

PubMed2004

Spearman's footrule as a measure of cDNA microarray reproducibility.

Replication is a crucial aspect of microarray experiments, due to various sources of errors that persist even after systematic effects are removed. It has been confirmed that replication in microarray studies is not equivalent to duplication, and hence it is not a waste of scientific resources. Replication and reproducibility are the most important issues for microarray application in genomics. However, little attention has been paid to the assessment of reproducibility among replicates. Here we develop, using Spearman's footrule, a new measure of the reproducibility of cDNA microarrays, which is based on how consistently a gene's relative rank is maintained in two replicates. The reproducibility measure, termed index.R, has an R2-type operational interpretation. Index.R assesses reproducibility at the initial stage of the microarray data analysis even before normalization is done. We first define three layers of replicates, biological, technical, and hybridizational, which refer to different biological units, different mRNAs from the same tissue, and separate cDNAs from a cDNA pool. As the replicate layer moves down to a lower level, the experiment has fewer sources of errors and thus is expected to be more reproducible. To validate the method we apply index.R to two sets of controlled cDNA microarray experiments, each of which has two or three layers of replicates. Index.R shows a uniform increase as the layer of the replicates moves into a more homogeneous environment. We also note that index.R has a larger jump size than Pearson's correlation or Spearman's rank correlation for each replicate layer move, and therefore, it has greater expandability as a measure in [0,1] than these two other measures.

Cell Line, Tumor↗

PubMed2004

Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus.

Although gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers, few studies have explored this possibility for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 protein is highly expressed in uterine cervical cancer tissues, but not in normal cervix, we constructed a tumor-specific replication-competent adenoviral vector utilizing MN/CA9 promoter (Ad-MN/CA9-E1a), which can replicate only in MN/CA9-expressing cells. Infection of Ad-MN/CA9-E1a to MN/CA9-positive uterine cervical cancer cells (HeLa, C-33 A and SiHa) resulted in much stronger Ad5 E1a protein expressions compared with MN/CA9-negative cells (SK-RC-29), suggesting a tissue-specific replication of this recombinant adenovirus. In vitro cytotoxicity assay revealed that the growth of MN/CA9-positive cells was significantly inhibited with 0.01-1 MOI of Ad-MN/CA9-E1a, but the growth of MN/CA9-negative cells (SK-RC-29) could only be inhibited by as many as 100 MOI. Intratumoral injection of Ad-MN/CA9-E1a effectively induced growth delay of HeLa tumors in nude mice. These results suggest that a novel replication-competent adenoviral vector mediated by MN/CA9 promoter, Ad-MN/CA9-E1a, can selectively replicate in MN/CA9-expressing tumors with cytotoxic effects and may be utilized for the treatment of uterine cervical cancer.

Adenoviridae↗