Prognostic factors in lung cancer.
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ABO Blood-Group System↗
Biomedical subjects
J S Lee
Publications and source records attributed to J S Lee.
Improved therapeutic index by leucovorin of edatrexate, cyclophosphamide, and cisplatin regimen for non-small-cell lung cancer.
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Aminopterin↗
Determination of biomarkers for intermediate end points in chemoprevention trials.
Renewed interest is being directed toward chemoprevention as a means of reducing cancer mortality. To overcome the inherent problems associated with using cancer development as a study end point, there has recently been a great surge of interest in defining the biomarkers associated with specific stages of the carcinogenic process as intermediate end points. We have detailed the evidence supporting the concept of field cancerization, a concept of general importance that is probably applicable to carcinogenesis and chemoprevention at many organ sites in humans, and presented results of tests of the potentially useful biomarkers proliferating cell nuclear antigen and blood group antigen. Because microassay techniques are more readily applicable to small biopsy samples, further expansion of these studies and exploration of panels of additional biomarkers are expected to generate exciting results in the field of chemoprevention.
ABO Blood-Group System↗
Genetic complexity of regulatory mutants defective for HLA class II gene expression.
MHC (called HLA in man) class II genes play an essential role in cell-mediated immunity. Absence of HLA class II Ag on B lymphocytes is the basis of some congenital immunodeficiencies (CID). We have studied CID by generating transient heterokaryons from cell lines of such patients, and we report that the mutations fall into four complementation groups. In addition, fusions with the HLA class II deletion mutant 721.180 indicate that the genetic defects for each group in HLA class II expression map outside the HLA class II region. A small HLA-DRA promoter fragment is sufficient to drive expression of a reporter gene in normal B cell lines, but expression from the same construct is clearly reduced in mutant cell lines representative of all four complementation groups. This confirms earlier results that indicate defective transcription of HLA class II genes in the class II- CID mutant cell lines. Analysis of proteins that bind to the DRA promoter in nuclear extracts of the mutants suggests that complexes recognizing distinct elements of the DRA promoter may be quantitatively decreased in different mutants. In addition, we show that nuclear extracts from two groups fail to transcribe a DRA promoter construct in vitro accurately reflecting their DRA- phenotypes. In contrast, nuclear extracts from another mutant, RJ2.2.5, transcribe the DRA construct, albeit at a reduced level. Finally, though cell lines from different groups complement each other in vivo, no complementation was observed by mixing extracts for transcription in vitro.
Base Sequence↗
Sarcomatoid carcinoma of the lung. Immunohistochemical and ultrastructural studies of 14 cases.
The authors retrospectively reviewed data regarding 14 patients with sarcomatoid carcinomas of the lung seen and treated at M.D. Anderson Cancer Center from 1955 to 1986. The following were the histologic criteria for inclusion in the study: (1) the concurrent presence of malignant epithelial and sarcomatoid spindle cell components, and (2) positive immunoreactivity for antikeratin antibody or ultrastructural demonstration of epithelial differentiation in sarcomatoid tumors in which the epithelial component was inconspicuous. For the sarcomatoid components, the most frequent pattern was malignant fibrous histiocytoma, which was present in ten tumors. An unclassified sarcomatoid pattern was found in two cases and a fibrosarcomatous pattern in two remaining cases. Clinically, the median patient age was 59 years; 12 patients were male and 2 were female; 13 were smokers and 1 used snuff. Three patients had Stage I, ten had Stage III, and one had Stage IV disease. One patient with Stage I, seven with Stage III, and one with Stage IV disease died of their carcinomas 2 to 26 months after diagnosis (median survival time 12 months). All patients who had lymph node metastases at presentation died of disease. The authors concluded the following: (1) patients with sarcomatoid carcinoma of the lung usually presented at an advanced stage; (2) lymph node metastasis, as with a usual carcinoma of the lung, is an important prognostic factor; and (3) for all lung tumors with a sarcomatoid pattern, especially a malignant fibrous histiocytoma pattern, extensive samples should be obtained and immunoperoxidase or ultrastructural studies done to identify epithelial differentiation.
Adult↗
Intermediate biomarkers in upper aerodigestive tract and lung chemoprevention trials.
Chemoprevention trials in lung and upper aerodigestive tract (UADT) cancer are guided by the field cancerization hypothesis. Inhaled carcinogens place the entire epithelial lining at risk for the development of cancer. The hypothesis is supported by the occurrence of premalignant lesions, such as leukoplakia or squamous metaplasia, and multiple primary tumors within the field. The concept of carcinogenesis as a multistep process suggests the possibility of blocking or reversing the progression to invasive cancer with systemic treatment. A series of ongoing clinical trials will determine the efficacy of retinoid chemoprevention and will attempt to develop intermediate biomarkers. Biomarkers which reliably reflect progression towards cancer could be used to dramatically improve the efficiency of chemoprevention trials and also would aid in screening potential chemoprevention agents. Genomic biomarkers include non-specific estimates of ongoing DNA injury, such as micronuclei, as well as development of aneuploidy and alterations in oncogenes. A class of biomarkers of increasing importance assess proliferation and growth regulation, and include proliferating cell nuclear antigen (PCNA), TGF-beta, EGFR and retinoid receptors. Other markers, such as the blood group antigens, reflect differentiation and may be associated with the development of premalignant lesions. Preliminary data from several of these markers has suggested an association with carcinogenic exposures and premalignant lesions, but none of these markers either alone or in panels have yet been validated as a reliable surrogate for the development of invasive cancer.
Anticarcinogenic Agents↗
Expression of alternatively spliced HLA class II transcripts in lymphoid and nonlymphoid tissues.
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Alleles↗
A cDNA clone for a novel nuclear protein with DNA binding activity.
In an effort to identify trans-acting factors regulating specific genes, we cloned a novel human gene, DBP-5. The cDNA clone contains a predicted open reading frame coding for a potential 1,179 amino acid protein. The mRNA corresponding to DBP-5 is ubiquitously distributed, and the gene is phylogenetically conserved. Immunofluorescence analyses with several cell lines indicate that the protein is localized to the nucleus. Sequence analysis revealed unusual features of the predicted protein structure, including four completely conserved repeats. The phylogenetic conservation of DBP-5, the ubiquity of its expression, its nuclear localization, and its ability to bind DNA sequences, raise the possibility that DBP-5 may play a role in the organization of interphase chromatin and/or in transcriptional regulation.
Amino Acid Sequence↗
A density method for determining plasma and red blood cell volume.
We employed a highly sensitive density measuring system to measure the decrease in blood density and plasma density due to the infusion of a saline bolus into the rabbit's circulation. Based on a vasculature model with the Fahraeus effect, we deduced a set of equations to calculate from the density decreases the red-blood-cell volume and plasma volume of the rabbit. A value of 0.82 +/- 0.02 was obtained for Fcell, the ratio of the hematocrit calculated from the two volumes and the arterial hematocrit.
Animals↗
Baseline frequency of sister-chromatid exchanges in 142 persons of the general Korean population.
Baseline frequencies of sister-chromatid exchange (SCE) were measured in lymphocytes of 142 healthy Koreans ranging in age from newborn infants to the fifties. The overall mean frequency of SCE was 8.78 +/- 0.24/cell. However, highly significant differences were found between individuals. The mean SCE values of the newborn babies and small children less than 10 years old were significantly lower than those of other age groups. No age effect was, however, observed in adolescent and adult subjects. Females had statistically higher SCE levels than males. The mean SCE frequencies of smokers, measured in male subjects more than 10 years old, were slightly, but statistically significantly, higher than those of non-smokers.
Adolescent↗
In vitro rheological evaluation of antithrombogenicity or anticoagulability of styrene derivative polymer.
In vitro evaluation of antithrombogenicity or anticoagulability of styrene derivative polymer with functional silyl groups, the polymer treated with acid, polystyrene and glass as a reference was attempted using a rheological method. The results were compared with those obtained from measurements of platelet adhesion. The coagulation process of blood in polymer-coated tubes was monitored using a damped oscillation-type rheometer recently developed. The change of fluidity during coagulation of blood was dependent on the polymers. Poly((4-vinylphenyl)dimethyl-2-propoxysilane) (poly(1)) was more antithrombogenic than polystyrene and acid-treated poly(1). The evaluation of antithrombogenicity or anticoagulability for the polymers and glass by the rheological method coincided well with that obtained from other methods. Furthermore, it was confirmed that the rheological method would be useful for elucidating mechanisms of coagulation of blood as well as thrombus formation in developing artificial blood-compatible materials.
Adult↗
Diabetic nephropathy: duplex Doppler ultrasound findings.
To evaluate the correlations among Doppler sonographic findings, morphologic sonographic findings, and laboratory findings representing renal functional status, duplex Doppler sonography of the kidney was performed in 32 patients with diabetes mellitus. Resistive indices obtained in the region of the arcuate or the interlobar arteries in patients with elevated serum creatinine levels were significantly higher than those in patients with normal serum creatinine levels (P < 0.05). Also, there was a significant correlation between the resistive indices and creatinine clearance levels (correlation coefficient, -0.828). There was a significant difference between the serum creatinine levels of patients with normal renal cortical echogenicity and those with increased cortical echogenicity (P < 0.05). Analysis of the Doppler spectrum of the intrarenal arteries in conjunction with careful evaluation of the renal cortical echogenicity may be helpful in sonographic prediction of the renal functional status in patients with diabetes mellitus.
Albuminuria↗
Combination of 5-fluorouracil and recombinant interferon alpha-2B in advanced gastric cancer. A phase I study.
Based on recent preclinical data suggesting synergism between 5-fluorouracil (5-FU) and interferon alpha (IFN-alpha) and clinical activity of the combination therapy in colon cancer, 14 patients with advanced gastric cancer were treated with combination therapy of 5-FU and recombinant interferon alpha-2b (rIFN alpha-2b) (Intron A, Schering, Kenilworth, NJ, U.S.A.). The maximum tolerated dose was 5-FU 750 mg/m2/day given as a continuous infusion daily for 5 days followed by weekly bolus injection of the same initial daily dose, plus rIFN alpha-2b 5 X 10(6) U given subcutaneously 3 times weekly starting day 1 of 5-FU infusion. The dose-limiting toxicities were fatigue/weakness, diarrhea, and neurologic toxicities such as somnolence and confusion. The other common side effects were nausea, fever, leukocytopenia, thrombocytopenia, and the darkening of the skin. Of 13 evaluable patients, 4 had a partial response (duration 6, 14, 24, and 28 weeks). These data suggest that combination therapy of 5-FU plus rIFN alpha-2b is tolerable and has manageable side effects in patients with advanced gastric cancer. Further Phase II study will be needed to define the antitumor activity of this combination.
Adult↗
Phase II study of combination therapy with high-dose cisplatin, etoposide, and mitomycin in patients with advanced non-small-cell lung cancer.
Forty-six patients with metastatic non-small-cell lung cancer (NSCLC) were treated with a combination of high-dose cisplatin, etoposide, and mitomycin. Thirty-four patients (74%) had a performance status of 1, and 39 patients (85%) had adenocarcinoma. Of the 42 patients evaluable for response and toxicity, four achieved a partial response (10%); no patient achieved a complete response. Seven patients who had received prior chemotherapy showed no major response. The median survival of all 42 patients was 23 weeks. Myelosuppression was the major dose-limiting toxicity for this regimen, and 12 of 46 patients (26%) developed neutropenic fever requiring hospitalization and parenteral antibiotics. Of the 12 patients with severe neutropenic fever, one patient died because of toxicity. Nonhematologic toxicities, including azotemia, peripheral neuropathy, nausea, vomiting, and hearing loss were transient and modest. We conclude that high-dose cisplatin combined with etoposide and mitomycin is a relatively toxic regimen with a low response rate. Further evaluation of the combination as given in this trial is not warranted.
Adult↗
Clinical variability of type 1 neurofibromatosis: is there a neurofibromatosis-Noonan syndrome?
Detailed clinical, ophthalmological, and molecular studies were performed on a multigeneration family in which there were many subjects with type 1 neurofibromatosis, a common autosomal dominant disorder. Affected family members displayed a wide range of clinical findings including, in two subjects, features seen in Noonan syndrome (triangular facies, downward slanting palpebral fissures, micrognathia, short stature, and learning disability). Subjects have been described previously whose features have overlapped with neurofibromatosis and Noonan syndrome, and it has been suggested that these persons might represent a separate condition. DNA haplotype analysis showed linkage of the neurofibromatosis phenotype seen in this family to the proximal long arm of chromosome 17 in the region where the type 1 neurofibromatosis gene has been mapped. These results imply that the Noonan phenotype seen in some patients with type 1 neurofibromatosis might be the result of variable or variant expression of the neurofibromatosis gene on chromosome 17. The possible role of non-specific factors, such as fetal hypotonia, in producing the neurofibromatosis-Noonan phenotype needs further investigation. The availability of closely linked and intragenic molecular markers for neurofibromatosis could potentially be useful in the diagnosis and characterisation of patients and families with atypical forms of neurofibromatosis.
Adult↗
Fibrosing alveolitis: prognostic implication of ground-glass attenuation at high-resolution CT.
To evaluate the prognostic implication of ground-glass attenuation at high-resolution computed tomography (HRCT) in assessing response to treatment in fibrosing alveolitis, the authors correlated HRCT findings with the improvement in pulmonary function, as represented by the increase in percentage predicted values on pulmonary function tests after corticosteroid therapy. Nineteen patients underwent HRCT before treatment and pulmonary function testing before and after treatment. The HRCT scans were reviewed by two independent observers. Areas of ground-glass attenuation were quantified subjectively by using a 0%-100% scale with 10% increments. The extent of ground-glass attenuation at HRCT was significantly correlated with improvement in diffusing capacity for carbon monoxide (r = .67, P = .0019), forced vital capacity (r = .71, P = .0007), and forced expiratory volume in 1 second (r = .64, P = .0034) after steroid treatment. These results suggest that ground-glass attenuation at HRCT is a good predictor of response to treatment in fibrosing alveolitis.
Adrenal Cortex Hormones↗
Fluid restitution and shift of blood volume in anesthetized rabbits subject to cyclic hemorrhage.
We investigated the effect of a 10% cyclic blood volume change with a period of 2 or 4 min to study the short-term control of blood volume. In experiments with pentobarbital-anesthetized rabbits, the blood density variation over a 2-min cycle is 0.94 +/- 0.04 (SE) g/l, and the plasma density variation is 0.17 +/- 0.04 g/l. The plasma density variation could result from a fluid restitution from the extravascular space (with a density 1,005 g/l), with a volume equal to 14% of the withdrawn blood volume. This restitution cannot account, however, for the entire observed density change in arterial blood. Because of the Fahraeus effect in microvascular flow, a shift in blood volume from the microvasculature is another mechanism that could lead to a decrease in the density of arterial blood. An analysis of the blood and plasma density variations indicates that a blood volume (49% of the shed volume) is shifted from the micro- to macrocirculation. This volume compensation by fluid restitution and volume shift acts to minimize the effect of hemorrhage on the filling of the venous system. We found that the blood density waveform parallels the change in blood volume. When the blood volume change reverses its direction, the density change also reverses direction with a time delay less than 8 s. The blood density variations are not altered by bilateral vagotomy or its combination with hexamethonium (a sympathetic ganglionic blocker). These observations of anesthetized rabbits indicate that the short-term compensation is primarily due to the volume shift from the microcirculation and is not regulated by humoral or neural mechanisms but by local mechanisms such as autoregulation and the passive response due to changes in microvascular pressure.
Anesthesia↗
The incidence of second primary tumors in long-term survivors of small-cell lung cancer.
PURPOSE AND METHODS: A review of 446 patients who were enrolled consecutively in small-cell lung cancer (SCLC) protocols was performed to identify in long-term survivors the frequency of new primary tumors and their clinical impact. RESULTS: Forty-seven patients (10.5%) were identified to be free of disease at 2 years. Second primary tumors (SPTs) were diagnosed in 14 patients. The overall risk for developing an SPT was 10.3% per person-year. Actuarial risk at 8 years was 50.3% for an SPT. CONCLUSIONS: In this review, SCLC showed one of the highest incidences of SPTs reported in aerodigestive tract malignancies. A long-term survivor was more likely to have an SPT than a relapse of SCLC. Consequently, the odds of death from an SPT compared with that from a relapse increased sharply from 1:13 within 4 years from diagnosis to 8:1 afterwards. Long-term survivors of SCLC would be excellent candidates for chemoprevention trials.
Adult↗