Biomedical subjects

B C Liang

Publications and source records attributed to B C Liang.

29 records · Page 2Linked to original sources

PubMed1995

Genomic copy number changes of DNA repair genes ERCC1 and ERCC2 in human gliomas.

Abnormalities of the genomic region of chromosome 19q13.2-13.4 are a common occurrence in brain malignancies and contain a possible tumor suppressor gene involved in gliomas. Since abnormalities of DNA repair are associated with malignancy, we assessed DNA status of the nucleotide excision repair genes located in this area, viz. ERCC1 and ERCC2. Radiodensitometry was used to assess gene copy number in samples obtained from brain tumor specimens from 24 patients. Nine tumors were of lower grade histology (3 pilocytic astrocytomas, 2 gangliogliomas, 4 astrocytomas); 15 tumors were pathologically higher grade (4 anaplastic astrocytomas, 11 glioblastomas). Tumor samples were obtained prior to radiation or chemotherapy. Abnormalities of gene copy number of ERCC1 and ERCC2 were observed in 11/24 specimens (46%). Whereas increased and decreased copy numbers were observed for ERCC1, only decreases in copy number of ERCC2 were seen. Three tumors (all lower grade) showed concurrent allelic loss of ERCC1 and ERCC2. Abnormalities of copy number for these genes were not associated with response to subsequent therapy nor survival. However, allelic loss of ERCC2 was associated with younger age at diagnosis when compared to those specimens which did not show loss. There were no significant differences between lower grade and higher grade tumors with respect to these investigations. Abnormalities in copy number of ERCC1 and ERCC2 are common in glial tumors. Further study of this genomic region is necessary to define the importance of these observations in tumor pathophysiology and treatment.

Adult↗

PubMed1995

Gene amplification elucidated by combined chromosomal microdissection and comparative genomic hybridization.

Gene amplification is an important manifestation of genetic instability in cancer. Recently, the study of gene amplification has been greatly facilitated by the development of the molecular cytogenetic techniques of comparative genomic hybridization and chromosome microdissection. We describe in this brief overview a combined approach using both techniques, which allows the identification of chromosomal regions of gene amplification and provides entry point clones for target gene identification. This molecular/cytogenetic approach consisting of chromosome microdissection and comparative genomic hybridization should be valuable in identifying novel amplified genes important in neoplastic development and progression.

Chromosomes↗

PubMed1995

Use of 'long' polymerase chain reaction and magnetic beads for extraction of chromosome-specific cDNAs.

The detection of expressed sequences of genomic DNA is an important aspect of the human genome project. A technique is described where 'long' polymerase chain reaction (LPCR), which allows for extended large fragment production of > 10-20 kb, is used with Alu primers to generate a biotinylated template for cDNA hybridization. Streptavidin-coated magnetic beads are used to extract the long PCR templates and bound cDNAs, which are recovered by standard PCR. This method allows the isolation of cDNAs from virtually any human DNA source and should be valuable in expression mapping, positional cloning and gene isolation.

Base Sequence↗

PubMed1995

Age influences chemotherapy response in astrocytomas.

OBJECTIVE: In patients with cerebral astrocytomas treated with nitrosourea-based chemotherapy, to determine whether age is predictive of response, time to progression, survival, or rate of complications. DESIGN: Retrospective analysis of neuroimaging studies and clinical data. SETTING: University hospital with a busy neuro-oncology service. PATIENTS: One hundred forty-eight patients with pathologically confirmed malignant astrocytomas or recurrent astrocytomas. RESULTS: Partial response occurred in 39% of patients aged < 40 years, in 17% of those aged 40 to 59, and in only 5% of those aged > or = 60 (p < 0.001). Median time to progression after chemotherapy was 23 weeks in patients aged < 60 and 6 weeks in patients aged > or = 60 (p < 0.001). Median survival after chemotherapy was 43 weeks in patients aged < 60 but only 24 weeks in patients aged > or = 60 (p < 0.001). Differences between age groups in response rate, time to progression, and survival persisted with adjustment for tumor grade. The risk of myelosuppressive complications requiring hospitalization was significantly related to age (p = 0.03); such complications occurred in 35% of patients aged > or = 60 and 16% of patients under 60 years. CONCLUSION: Age is strongly predictive of the likelihood of a response to chemotherapy, time to progression, survival, and risk of myelosuppressive complications. Patients aged > or = 60 have a lower change of benefit and an increased risk of myelosuppressive complications from chemotherapy for astrocytomas compared with younger patients.

Adolescent↗

PubMed1994

Paraneoplastic pseudo-obstruction, mononeuropathy multiplex, and sensory neuronopathy.

A patient with mononeuropathy multiplex, sensory neuronopathy, and diffuse intestinal pseudo-obstruction consisting of gastroparesis and impaired small and large bowel motility was found to have a small cell carcinoma of the lung. The constellation of findings were indicative of paraneoplastic neuropathy, which was confirmed with the appropriate antibody studies demonstrating antineuronal nuclear antibodies. Identification of paraneoplastic neuropathy is important, since early treatment of the primary cancer, which is virtually always a small cell carcinoma of the lung, may halt the progression of the disorder.

Aged↗

PubMed1994

Evidence of allelic imbalance of chromosome 6 in human astrocytomas.

Transfer of human chromosome 6 can suppress the malignant phenotype of melanoma. Because of the neural ectoderm origin of melanoma and since up to 30% of gliomas have abnormalities involving chromosome 6, we performed restriction fragment length polymorphism analysis to determine the importance of allelic loss on chromosome 6 in gliomas. DNA samples from tumor and white blood cells were obtained from patients with pathologically verified gliomas. Of the 20 paired samples, there were two gangliogliomas and one grade I, four grade II, two tumors labeled "low grade," two grade III, and nine grade IV astrocytomas. DNA was hybridized with polymorphic probes D6S29 (6p21), c-myb (6q23.3-24), SOD2 (6q25), D6S37 (6q26), and ESR (6q27). All grades of tumor revealed areas of genetic loss. Allelic imbalance (AI) was present in 11 of 47 (23%) of informative loci on 6q and four of seven (57%) on 6p. Loci at 6p21 and 6q26 were most often lost. In contrast, probes from three non-chromosome 6 loci demonstrated a combined total of 11% allelic loss. Genetic loss from chromosome 6 is a frequent event in glial neoplasms.

Alleles↗

PubMed1994

Using dyes and filters in a fluorescent imaging system.

The FluorImager fluorescence imaging system uses monochromatic 488-nm laser light to excite fluorochromes. It contains a built-in 515-nm long-pass filter that rejects excitation laser light, but allows emission light with wavelengths longer than 515 nm to pass through. A fluorochrome appropriate for use in the system is excitable by 488-nm light and emits at least some of its fluorescence at wavelengths longer than 515 nm. Two types of optical filters, long-pass and band-pass, are used in the system. Long-pass filters reject shorter wavelengths and transmit longer wavelengths. The number in the filter name denotes the cutoff wavelength (midpoint of the transition between rejected and transmitted light) for the filter. Band-pass filters transmit a band of wavelengths and reject both shorter and longer wavelengths. The numbers in the filter name denote the center wavelength of the passed band and the width of the band at half maximum transmission. Generally, when scanning for a single fluorochrome, only the built-in 515-nm long-pass filter is needed. An interchangeable filter can be added to decrease the contribution from a broad-spectrum background signal and to attenuate strong fluorochrome signals.

Calcium↗

PubMed1992

A Drosophila model for xeroderma pigmentosum and Cockayne's syndrome: haywire encodes the fly homolog of ERCC3, a human excision repair gene.

The haywire gene of Drosophila encodes a protein with 66% identity to the product of the human ERCC3 gene, associated with xeroderma pigmentosum B (XP-B) and Cockayne's syndrome (CS). XP is a human autosomal recessive disease characterized by extreme sensitivity to ultraviolet irradiation and marked susceptibility to skin cancer. In addition, XP and CS patients often exhibit a variety of defects, ranging from central nervous system disorders to hypogonadism. Phenotypes of haywire mutants mimic some of the effects of XP. Many haywire alleles are recessive lethal, viable alleles cause ultraviolet sensitivity, and files expressing marginal levels of haywire display motor defects and reduced life span. Progeny of females carrying a maternal effect allele show central nervous system defects.

Amino Acid Sequence↗

PubMed1991

Malignant astrocytomas: focal tumor recurrence after focal external beam radiation therapy.

Hochberg and Pruitt have reported glioblastomas recurring within 2 cm of the primary site in 90% of patients after whole-brain radiation therapy. They suggested that computerized tomography (CT) scan accuracy would permit smaller radiation fields. A treatment protocol with smaller-field focal brain irradiation following surgical resection is reported. The first 4500 cGy of radiation is focused to within a 3-cm margin around the tumor, with a 1500-cGy boost within a 1.5-cm margin. Forty-two patients with grade III or IV astrocytoma, treated with focal brain radiation therapy were reviewed retrospectively to assess patterns of tumor recurrence. Thirty patients received intra-arterial bromodeoxyuridine (BUdR) radiosensitization with focal brain radiation therapy, and 12 patients underwent conventional focal brain radiation therapy. Tumor margin was defined on preoperative and recurrence CT scans as the contrast-enhanced area; these were traced on acetate templates and compared with each other and with the actual scans. In all 42 patients, the lesion recurred within a 2-cm margin of the original tumor. Four patients had two recurrent areas: the second area was within the 2-cm margin in two, and outside this margin in two. These results are similar to those of Hochberg and Pruitt. It is suggested that focal irradiation is now the optimal treatment for malignant astrocytoma. Since recurrences continue to be within the irradiated volumes, it appears that higher focal doses of radiation are appropriate for clinical treatment trials of malignant astrocytomas.

Brain Neoplasms↗

PubMed1987

Effects of alkylxanthines and calcium antagonists on adenosine uptake by cultured rabbit coronary microvascular endothelium.

Adenosine uptake by cultured rabbit coronary microvascular endothelial cells was studied. Radiolabeled [2-3H]-adenosine, present initially in the extracellular space at 10(-6) mol/l, was incorporated into the cell cultures at a steady rate during 30 s-3 h incubations. Incorporated 3H was found mostly (83%) in adenine nucleotides. Incorporation of [3H]-adenosine was attenuated by an adenosine deaminase inhibitor (EHNA) but only at adenosine concentrations of 10(-5) mol/l or higher. Adenosine transport inhibitors (dipyridamole, nitrobenzylthioinosine) attenuated 3H incorporation. Adenosine uptake was also diminished by certain structural analogues of adenosine (e.g., 2-chloroadenosine), by several alkylxanthine drugs (theophylline, isobutylmethylxanthine, enprofylline and 8-phenyltheophylline), and by certain calcium antagonists (verapamil, nifedipine and trifluoperazine). The mechanisms of actions of these agents on adenosine uptake do not appear to be related to phosphodiesterase inhibition, adenosine receptor antagonism or calcium antagonism. The effects of varying adenosine metabolism may contribute to the pharmacologic actions of these agents.

1-Methyl-3-isobutylxanthine↗

PubMedDate not supplied

2',3'-Dideoxycytidine is a potent inducer of apoptosis in glioblastoma cells.

The effect of 2',3'-dideoxycytidine (ddC) treatment on two human glioblastoma cell lines was characterized. ddC treatment (10 nM-100 microM) of glioblastoma cells was associated with enlargement and shortening of processes within 2-3 days. Assessment of mitochondrial membrane potential showed an early decrease in the number of polarized mitochondria in the glioma cells, at between 16 to 84% of the untreated control. With chronic exposure to varying doses of ddC, the tumor cells underwent apoptosis within 5-32 days. This apoptosis was dramatic, with a complete loss of cell viability in < 6 hours after cells were noted to begin detaching from the tissue culture flask. Supplementation with uridine, pyruvate and glucose could delay cellular death at the lower doses of ddC (10 nM to 15 microM) but not at the higher doses. However, regardless of supplementation, all cells eventually underwent apoptosis. ddC is a potent inducer of apoptosis in human glioblastoma cells. Assessments of efficacy in in vivo models and clinical trials should be performed to determine the value of ddC in the treatment of malignant brain tumors.

Antimetabolites↗