Biomedical subjects

E T Liu

Publications and source records attributed to E T Liu.

81 records · Page 5Linked to original sources

PubMed1992

Prevalence of human papillomavirus types 16 and 18 in squamous-cell carcinoma of the penis: a retrospective analysis of primary and metastatic lesions by differential polymerase chain reaction.

Human papillomaviruses (HPV), particularly types 16 and 18, may be carcinogenic effectors in a variety of human lower-genital-tract malignancies. Using the highly sensitive technique of differential polymerase chain reaction (D-PCR) with amplimers from the E6 open reading frames of HPV types 16 and 18, a retrospective analysis of a 20-year institutional experience with squamous-cell carcinoma of the penis (SCCP) was performed to determine the prevalence of these HPV types in this malignancy. Paraffin-embedded surgical specimens of primary (N = 27), locally recurrent (N = 5), and metastatic deposits (N = 26) from 29 patients with invasive SCCP were analyzed, as well as primary (N = 3) and recurrent (N = 2) specimens from 2 patients with penile carcinoma in situ (CIS) (Bowen's disease). Nine of the 29 (31%) patients had invasive SCCP containing HPV 16 or 18 DNA, with HPV 16 found in 8 (28%) and HPV 18 in I (3%); no patient had both. In 7 patients in which only tissue from metastatic sites was available, 2 had HPV 16 detected in 2 separate metastatic sites each. Specimens from both primary and metastatic sites were available in an additional 6 patients, and HPV 16 was detected in specimens from 3 of these 6 patients. HPV was detected in comparable copy number at both sites in each patient, indicating that HPV DNA may be a stable component within cancer cells during disease progression. Of patients with CIS only, 1 of 2 was positive for HPV 16, and upon multifocal recurrence, showed persistence of the virus at 2 separate sites. Southern blotting was performed to confirm the presence of type-specific HPV DNA and showed complete concordance with D-PCR, but discordant hybridization intensities for HPV 18 were noted between the control and positive patient specimens; sequence analysis of the patient specimen revealed 4 point mutations in the HPV-18 target segment. Comparison of the HPV-positive (both HPV 16 and HPV 18) and HPV-negative groups revealed no statistical differences between groups in patients age or ethnic origin, tumor histologic grade, or incidence of nodal involvement. Kaplan-Meier analysis of both overall and cause-specific survival likewise was not different between groups. These data, particularly the presence of HPV in metastatic deposits, provide strong evidence for an etiologic role of HPV type 16 (and possibly 18) in a substantial sub-set of patients from the southeastern United States who developed SCCP.

Aged↗

PubMed1992

Expression polymerase chain reaction: a sensitive method for analysis of gene expression in human tumours.

To analyse the expression of individual genes in small tumour samples, we have used the method of RNA polymerase chain reaction (PCR) to develop a technique which we have termed expression PCR. With this technique, specific cDNA sequences of a target gene are amplified, analysed by gel electrophoresis, and semi-quantitated using laser densitometry. Alpha-actin is amplified as a reference gene to control for template RNA and each target gene is analysed at several cycle numbers to optimize PCR dynamics. In this study, we have demonstrated expression PCR by analysing the levels of expression of tyrosine kinase genes in a panel of human tumours. We have compared expression PCR with Northern analysis to show that these techniques provide equivalent information on relative levels of gene transcription, with expression PCR requiring 100-fold less RNA. This technique is sufficiently sensitive to detect and compare the levels of expression of genes not seen on Northern analysis and is ideally suited for analysing the expression of multiple genes within the same portion of a tumour.

Base Sequence↗

PubMed1992

Human papillomavirus types 16 and 18 are not involved in human prostate carcinogenesis: analysis of archival human prostate cancer specimens by differential polymerase chain reaction.

Human papilloma viruses (HPV) have been implicated in the pathogenesis of a variety of malignancies, especially in carcinomas of the female genital tract. Recently, based on observations using the polymerase chain reaction amplification assay, HPV types 16 and 18 specific DNA sequences have been detected in prostate cancer specimens obtained by transurethral resection. Since HPV types 16 and 18 have been shown to possess oncogenic potential, an association between HPV infection and prostatic carcinoma has been suggested. In order to exclude potentially HPV-colonized urethral mucosa from analysis and restrict our study to predominantly malignant tissue, cancerous areas from a series of 30 paraffin-embedded prostate adenocarcinomas were microdissected and analyzed for the presence of HPV 16 or HPV 18 specific sequences by a modification of PCR (D-PCR) and Southern blot analysis. Despite the high sensitivity of our analytical technique, we found no evidence of HPV-DNA of either type in any of the 30 primary prostate cancers. In contrast, both HPV 16 (2/8 specimens) and HPV 18 (2/8 specimens) DNA was detected in randomly chosen cervical carcinomas using the D-PCR methodology. Our data would indicate that the oncogenic HPV-types 16 and 18 are unlikely effectors of prostate carcinogenesis.

Adenocarcinoma↗

PubMed1992

Alterations of the P53 gene are associated with the progression of a human prostate carcinoma.

P53 is a tumor suppressor gene that has been implicated in the molecular genetics of many human malignancies. Nucleotide alterations, most commonly single point mutations, have been shown not only to abrogate the p53 suppressor function but also to contribute to the transformed phenotype. We report the detection of a p53 gene mutation in clinical specimens of a patient with relapsing prostate adenocarcinoma 14 years after definitive external beam radiation. The techniques of single strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction generated products were used for this study. Analysis of tissue from different locations of the primary tumor revealed intratumoral molecular heterogeneity; the mutation was absent in 1 area but present in another. Tumor from a regional lymph node metastasis harbored the identical p53 mutation. Furthermore, an additional genetic alteration, an allelic loss on chromosome 17p but not including the p53 gene, was observed only in the metastatic tissue. These observations in clinical specimens of primary and metastatic sites provide evidence for the association of the p53 gene in the progression of human prostate carcinoma.

Adenocarcinoma↗

PubMed1991

axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase.

Using a sensitive transfection-tumorigenicity assay, we have isolated a novel transforming gene from the DNA of two patients with chronic myelogenous leukemia. Sequence analysis indicates that the product of this gene, axl, is a receptor tyrosine kinase. Overexpression of axl cDNA in NIH 3T3 cells induces neoplastic transformation with the concomitant appearance of a 140-kDa axl tyrosine-phosphorylated protein. Expression of axl cDNA in the baculovirus system results in the expression of the appropriate recombinant protein that is recognized by antiphosphotyrosine antibodies, confirming that the axl protein is a tyrosine kinase. The juxtaposition of fibronectin type III and immunoglobulinlike repeats in the extracellular domain, as well as distinct amino acid sequences in the kinase domain, indicate that the axl protein represents a novel subclass of receptor tyrosine kinases.

Amino Acid Sequence↗

PubMed1990

The role of ras gene mutations in myeloproliferative disorders.

Mutations in the ras genes frequently are found in myeloproliferative disorders. These abnormalities have prognostic significance in the myelodysplastic syndromes, but their clinical importance in other hematopathic states remains unclear. The study of this gene in leukemic conditions is providing insights into the genetic pathways leading to leukemic progression.

Genes, ras↗

PubMed1986

Management of treatment failures in thrombotic thrombocytopenic purpura.

The prognosis and optimal management of patients with thrombotic thrombocytopenic purpura (TTP) who fail initial therapy with plasmapheresis or splenectomy are unclear. We report our experience with eight patients with TTP who did not respond to initial therapy. Seven patients achieved complete remission when alternate therapy was started soon after the recognition of initial treatment failure. One patient who received no alternative therapy died of progressive TTP. Our cases combined with those in the literature indicate a 74% salvage rate for patients who fail initial treatment for TTP. The combination of splenectomy, dextran, and steroids appears to be an effective treatment for patients with TTP who fail to respond adequately to plasmapheresis.

Adult↗

PubMed1985

The role of splenectomy in multimodality treatment of thrombotic thrombocytopenic purpura.

Current treatment modalities for thrombotic thrombocytopenic purpura (TTP) include plasmapheresis (PP), splenectomy, steroids, dextran, other antiplatelet agents, and vinca alkaloids. Prior to the development of PP and use of multimodality treatment for TTP, mortality rates exceeded 50%. This report reviews 11 patients treated for TTP, demonstrates the successful use of splenectomy as salvage therapy, and defines our indications for splenectomy in the treatment of this disorder. Ten of 11 patients were initially treated with PP; three responded completely and one died of fulminant disease. Six patients had a transient partial response to plasmapheresis and were subsequently treated with splenectomy, steroids, and dextran-70. Initial plasmapheresis resulted in improvement in laboratory values and clinical status in those patients requiring splenectomy. Durable remission (6-48 months) was achieved in 91% of patients with minimal morbidity.

Adult↗

PubMed1983

Serum myoglobin, ionized calcium, and parathyroid function during rhabdomyolysis.

The serum ionized calcium, phosphate parathyroid hormone, and myoglobin levels were observed in a patient with idiopathic hypoparathyroidism and rhabdomyolysis. Since calcium levels best correlate inversely with serum myoglobin and lactic dehydrogenase, we suggest that these two enzymes are better markers of the activity of rhabdomyolysis than serum creatine phosphokinase or SGOT. Furthermore, a non-hormonal, nonrenal mechanism is important in the fluxes of serum calcium and phosphate in rhabdomyolysis.

Calcium↗