ABSTRACT
PURPOSE: The behavior of invasive carcinomas in human can be very varied with different individual responses to chemotherapy. Individualization is crucial to the optimization of chemotherapy. Therefore, the prediction of a tumor's sensitivity to anticancer agents has been the subject of intensive investigation. In order to investigate the pathobiology of breast cancer, it is necessary to maintain or recreate the characteristics of the three-dimensional architecture of the tissues in culture. In this study, we have evaluated the relationship between the Histoculture Drug Response Assay (HDRA) assessment and chemotherapy responses in breast cancer patients. METHODS: Tumor specimens from 30 patients with breast cancer were evaluated using the HDRA. Tumor tissues were cultured on gelfoam sponge gel in 24-well plates, followed by treatment with a variety of chemotherapeutic agents. All treatments were conducted in triplicate. The sensitivity of a chemotherapy regimen was defined as a tumor inhibition rate (IR) in excess of 30%. Neoadjuvant or palliative chemotherapy for patients, using anthracycline or taxane, was conducted on the basis of the established protocols. The responses to treatments were compared with the results of the HDRA. RESULTS: The mean IR for the combinations of doxorubicin and docetaxel and for FAC and AC were 48, 45, and 36%, respectively. The above partial rate of response to chemotherapy was 81.1%. The sensitivity and specificity of the HDRA assessment, with a 30% inhibition rate, were 81.5 and 66.7%, respectively. The positive and negative response prediction values were 91.7 and 44.4%, respectively. The responses to treatments and the results of the HDRA assessment were not correlated with the expressions of the hormonal receptor or c-erbB2. CONCLUSION: In cases in which the inhibition rate is in excess of 30%, the HDRA assessment yielded a high positive response prediction value. The sensitivity to chemotherapy, as determined by the HDRA, appears to be a good guide for selection in breast cancer patients. Thus the results presented herein should be integrated into future research on the subject.
Subject(s)
Humans , Antineoplastic Agents , Breast Neoplasms , Breast , Doxorubicin , Drug Therapy , Gelatin Sponge, Absorbable , Porifera , Sensitivity and SpecificityABSTRACT
PURPOSE: The behavior of invasive carcinomas in human can be very varied with different individual responses to chemotherapy. Individualization is crucial to the optimization of chemotherapy. Therefore, the prediction of a tumor's sensitivity to anticancer agents has been the subject of intensive investigation. In order to investigate the pathobiology of breast cancer, it is necessary to maintain or recreate the characteristics of the three-dimensional architecture of the tissues in culture. In this study, we have evaluated the relationship between the Histoculture Drug Response Assay (HDRA) assessment and chemotherapy responses in breast cancer patients. METHODS: Tumor specimens from 30 patients with breast cancer were evaluated using the HDRA. Tumor tissues were cultured on gelfoam sponge gel in 24-well plates, followed by treatment with a variety of chemotherapeutic agents. All treatments were conducted in triplicate. The sensitivity of a chemotherapy regimen was defined as a tumor inhibition rate (IR) in excess of 30%. Neoadjuvant or palliative chemotherapy for patients, using anthracycline or taxane, was conducted on the basis of the established protocols. The responses to treatments were compared with the results of the HDRA. RESULTS: The mean IR for the combinations of doxorubicin and docetaxel and for FAC and AC were 48, 45, and 36%, respectively. The above partial rate of response to chemotherapy was 81.1%. The sensitivity and specificity of the HDRA assessment, with a 30% inhibition rate, were 81.5 and 66.7%, respectively. The positive and negative response prediction values were 91.7 and 44.4%, respectively. The responses to treatments and the results of the HDRA assessment were not correlated with the expressions of the hormonal receptor or c-erbB2. CONCLUSION: In cases in which the inhibition rate is in excess of 30%, the HDRA assessment yielded a high positive response prediction value. The sensitivity to chemotherapy, as determined by the HDRA, appears to be a good guide for selection in breast cancer patients. Thus the results presented herein should be integrated into future research on the subject.
Subject(s)
Humans , Antineoplastic Agents , Breast Neoplasms , Breast , Doxorubicin , Drug Therapy , Gelatin Sponge, Absorbable , Porifera , Sensitivity and SpecificityABSTRACT
PURPOSE: To investigate the variation in the chemosensitivity in soft tissue sarcoma (STS), fresh biopsy with sample for culture was tested using the histoculture drug response assay (HDRA)method. MATERIALS AND METHODS: 30 samples of fresh STS were obtained during either biopsy or surgical removal at our hospital between March, 2002 and March, 2004. RESULTS: Drug sensitivity testing by HDRA showed that two drug, Doxorubicin and CDDP, had a significantly higher inhibition rate than BLM, CTX, DTIC, VCR or VP-16 in the thirty STS tested. Doxorubicin showed the highest inhibition rate in the liposarcoma. CDDP shoewd the significant inhibition rate in the synovial sarcoma and malignant fibrous histiocytpma. Depending on the morphological type, round cell sarcoma and pleomorphic sarcoma were more sensitive to Doxorubicin and CDDP than spindle cell sarcoma. In the round cell sarcoma, BLM, CTX, VP-16 and IFS also showed above 30% inhibition rate. CONCLUSION: Drug sensitivity testing in STS should be evaluated with clinical outcome in the future and then HDRA will provide useful information for selection of an anticancer agent for STS because of its ease of evaluation and high predictability.
Subject(s)
Humans , Biopsy , Dacarbazine , Doxorubicin , Etoposide , Sarcoma , Sarcoma, SynovialABSTRACT
PURPOSE: Cancers are highly individual in their response to chemotherapy, however attempts to predict tumor response to drugs using in vitro cell culture have largely failed. A new technology, the histoculture drug response assay (HDRA), appears to have solved many previous problems. The purpose of this study is to evaluate the reliability of HDRA in a chemosensitivity test for breast cancer. MATERIALS AND METHODS: Tumor specimens from breast cancer patients were evaluated by HDRA using different chemotherapeutic agents. Each specimen was tested using a blind method in order to determine the reproducibility of HDRA results for the same tissue and with a triplicated assay in order to determine reproducibility by different examiners. The evaluative power of this assay and the chemosensitivity of drugs for each specimen was determined. RESULTS: Specimens of 92.9% (65/70) were successfully cultured and evaluated for chemosensitivity. The reproducibility of HDRA for the same tissue was 75% (100% agreement) and 100% (over 70% agreement), respectively. And the reproducibility by different examiners was 78.9% (100% agreement) and 94.7% (over 70% agreement), respectively. Each specimen demonstrated a response to at least one agent. CONCLUSION: The evaluative power and reproducibility of HDRA were high, therefore it might serve as a reliable clinical method for chemosensitivity testing. However, there is a need for clinical trial in which patients are initially randomized for treatment either by HDRA direction or by clinician's choice.
Subject(s)
Humans , Breast Neoplasms , Breast , Cell Culture Techniques , Drug TherapyABSTRACT
We have determined and analyzed the full-length cDNA sequence of a coxsackievirus B3 (CVB3) Korean isolate (CVB3-Korea/97) which has been known as a general human pathogen. The whole genome contains 7,400 nucleotides and has a single large open reading frame with 6,555 nucleotides that encodes a potential polyprotein precursor of 2,185 amino acids. The genome also contains a 5' non-coding region (NCR) of 741 bases and a 3' NCR of 104 bases followed by poly(A) tail. Sequence homologies of nucleotides and deduced amino acids between the CVB3-Korea/97 strain and the prototype (Nancy strain) were 81.7% and 91.5%, respectively. The genes encoding the functional proteins including viral protease and RNA dependent RNA polymerase showed higher homology than those encoding the structural proteins. We have further analyzed the sequences of 5' NCR, VP1 and VP2 of CVB3-Korea/97, which are known as cardiovirulent determining factors at the nucleotide and amino acid levels. Although the CVB 3-Korea/97 strain was isolated from an aseptic meningitis patient without cardiomyopathy, its 234th nucleotide and 165th amino acid were uracil and Asn as same as those of other cardiovirulent strains one. However, the 155th amino acid of VR1, which closely associated with cardiovirulence, was replaced with Arg155 by single nucleoptide substitution from A2916 to T2916. Moreover, additional amino acid substitutions were observed in the flanking region of Asp155. Taken together, aminoacid(s) substitution in VP1 may play a critical role in determining cardiovirulence of the CVB3-Korea/97 strain rather than individual nucleotide replacements in the 5' NCR and/or an amino acid substitution in VP2.
Subject(s)
Humans , Amino Acid Substitution , Amino Acids , Cardiomyopathies , Clone Cells , Cloning, Organism , DNA, Complementary , Genome , Korea , Meningitis, Aseptic , Nucleotides , Open Reading Frames , RNA-Dependent RNA Polymerase , RNA, Messenger , Sequence Analysis , Sequence Homology , UracilABSTRACT
BACKGROUND: To investigate the epidemiology of aseptic meningitis in Korea, we have isolated and characterized enteroviruses isolated from patients with acute meningitis from 1993 to 1998. METHODS: Stool and/or cerebrospinal fluid (CSF) samples from patients with aseptic meningitis were inoculated onto enterovirus-susceptible cell lines. The virus propagation was examined by the presence of cytopathic effects and each viral isolate was further characterized using a neutralization test. RESULTS: Out of 1,127 specimens, 197 enteroviral isolates were obtained mostly from stool samples (82.8 %) of children aged zero to ten years. At least 15 serotypes of enteroviruses, including echoviruses (EV) 3, 6, 7, 9, 25 and 30, coxsackieviruses (CV) B1~B6, and vaccine-derived polioviruses (PV) had circulated during the previous 6 years. The major serotypes that caused outbreaks of aseptic meningitis, were EV30 in 1997 and EV6 in 1998. Although the incidence of virus isolation peaked during summer, we had isolated enteroviruses all the year round in 1998. CONCLUSION: Since 1993, we had confirmed 197 cases of enteroviral meningitis. Outbreaks of aseptic meningitis were mainly caused by EVs, with peaks during the summer months. Our data emphasize that the nationwide surveillance of aseptic meningitis should be expanded and maintained throughout the year.
Subject(s)
Child , Humans , Cell Line , Cerebrospinal Fluid , Disease Outbreaks , Enterovirus B, Human , Enterovirus , Epidemiologic Studies , Epidemiology , Incidence , Korea , Meningitis , Meningitis, Aseptic , Neutralization Tests , PoliovirusABSTRACT
BACKGROUND: To investigate the epidemiology of aseptic meningitis in Korea, we have isolated and characterized enteroviruses isolated from patients with acute meningitis from 1993 to 1998. METHODS: Stool and/or cerebrospinal fluid (CSF) samples from patients with aseptic meningitis were inoculated onto enterovirus-susceptible cell lines. The virus propagation was examined by the presence of cytopathic effects and each viral isolate was further characterized using a neutralization test. RESULTS: Out of 1,127 specimens, 197 enteroviral isolates were obtained mostly from stool samples (82.8 %) of children aged zero to ten years. At least 15 serotypes of enteroviruses, including echoviruses (EV) 3, 6, 7, 9, 25 and 30, coxsackieviruses (CV) B1~B6, and vaccine-derived polioviruses (PV) had circulated during the previous 6 years. The major serotypes that caused outbreaks of aseptic meningitis, were EV30 in 1997 and EV6 in 1998. Although the incidence of virus isolation peaked during summer, we had isolated enteroviruses all the year round in 1998. CONCLUSION: Since 1993, we had confirmed 197 cases of enteroviral meningitis. Outbreaks of aseptic meningitis were mainly caused by EVs, with peaks during the summer months. Our data emphasize that the nationwide surveillance of aseptic meningitis should be expanded and maintained throughout the year.
Subject(s)
Child , Humans , Cell Line , Cerebrospinal Fluid , Disease Outbreaks , Enterovirus B, Human , Enterovirus , Epidemiologic Studies , Epidemiology , Incidence , Korea , Meningitis , Meningitis, Aseptic , Neutralization Tests , PoliovirusABSTRACT
No abstract available.
Subject(s)
Hepacivirus , Hepatitis C , Hepatitis , Korea , PrevalenceABSTRACT
No abstract available.