[Squamous cell cancer of the esophagus. Treatment concept at the Houston M.D. Anderson Cancer Center].
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
J A Roth
Publications and source records attributed to J A Roth.
Characterization of a Salmonella choleraesuis isolate after repeated neutrophil exposure.
Salmonella choleraesuis strain 38 (glycerol-positive fermentation) was repeatedly exposed to porcine neutrophils in an attempt to mimic in vivo conditions of the host immune system. After phagocytosis, viable intracellular S choleraesuis were isolated and the process was repeated at least 5 times. A fifth-passage strain-38 neutrophil-adapted clone, 38PMNa-5X, was isolated, and was compared with the parent wild-type strain 38 for changes. Strain 38PMNa-5X had increased resistance to killing by hydrogen peroxide and phagocyte killing by porcine neutrophils, as measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction. Strain 38PMNa-5X was less invasive than the parent strain on Vero cell monolayers, and had been cured of a 50-kb plasmid. The 50-kb plasmid was marked with bacteriophage mini-Mu (kanamycin resistant) and was reinserted into strain 38PMNa-5X. Strain 38PMNa-5X was avirulent in mice, but the isolates with reinserted plasmids had intermediate resistance to neutrophil and hydrogen peroxide killing and had restored invasiveness and mouse virulence. Differences in complement sensitivity and enzymatic activity were not observed between the strains.
Animals↗
In vivo isolation of Salmonella choleraesuis from porcine neutrophils.
Seventy-five pigs from 4 facilities were examined for Salmonella choleraesuis by use of bacteriologic culture of feces, blood, WBC (buffy coat), mononuclear leukocytes, and neutrophils. The organism was isolated from 0 of 75 fecal samples, compared with isolation from 39 of 75 purified neutrophil preparations. Of the pigs that did not have Salmonella isolated from feces or blood, but had S choleraesuis isolated from neutrophils, 6 were further examined. These pigs from 2 groups again had culture performed at least 3 successive times to test for repeatability and to determine optimal number of neutrophils required for Salmonella isolation. These same pigs were euthanatized and necropsied. Nineteen tissue specimens from each pig were obtained for culture, but S choleraesuis was isolated only from neutrophil samples. Results indicate that neutrophils may contribute to the carrier state in pigs and should be cultured when attempting to identify S choleraesuis carrier swine.
Animals↗
A simple and efficient method for isolation of DNA fragments from agarose gel.
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DNA↗
Exacerbation of ventricular arrhythmias during the postoperative period after implantation of an automatic defibrillator.
The postoperative course of 68 consecutive patients treated with an implantable defibrillator during the period from 1982 through 1990 was studied. In 46 patients (group 1), no concomitant surgery was performed during the implantation. In 22 patients (group 2), concomitant surgery (coronary artery bypass [n = 12], valve replacement [n = 3] or arrhythmia surgery [n = 7]) was performed. All patients in group 1 were clinically stable before surgery, receiving an antiarrhythmic regimen chosen by serial drug testings. The same regimen was continued postoperatively. Eight of the 46 patients in group 1 whose condition had been stable in the hospital for 19 +/- 25 days preoperatively developed multiple episodes of sustained ventricular tachycardia 4 +/- 9 days after implantation while receiving the same antiarrhythmic regimen. Although the exacerbation was transient in some patients, six required different antiarrhythmic therapy and one eventually died. Two additional patients had frequent and prolonged episodes of nonsustained ventricular tachycardia that could trigger the defibrillator, requiring changes in the antiarrhythmic regimen. Another patient had progressive cardiac failure and died on day 5. A marked (sevenfold) increase in asymptomatic ventricular arrhythmias was noted in 42% of the remaining 35 patients. In group 2 (combined surgery), one patient developed refractory ventricular tachycardia 3 days postoperatively and died on that day. Three patients developed frequent nonsustained ventricular tachycardia postoperatively, requiring changes in the antiarrhythmic regimen. The overall surgical mortality rate was 4.4% (4.3% in group 1 and 4.5% in group 2) and was due to refractory ventricular tachycardia in two patients and cardiac failure in one.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
p53 gene mutations in Barrett's epithelium and esophageal cancer.
Genomic DNA was extracted from archival pathology specimens comprising 10 squamous and 14 adenocarcinomas, including 7 with Barrett's epithelium adjacent to tumor, and corresponding normal esophagus from the resection margin. The polymerase chain reaction was used to amplify selected exons of p53 which were analyzed for mutations using single-strand conformation polymorphism analysis. Mutations were localized to exon 8 for 1 adenocarcinoma and to exon 5 for 1 squamous tumor and 4 of 7 Barrett's specimens. Sequencing confirmed mutations at codons 273 (CGT----CAT; adenocarcinoma) and 176 (TGC----TTC; squamous) and in Barrett's epithelium at codons 152 (CCG----CTG), 155 (ACC----GCC) and 175 (CGC----CAC). Specimens of Barrett's epithelium from separate sites had identical p53 mutations suggesting a clonal origin. Cancers arising in mutant epithelium did not have mutations corresponding to those found in the Barrett's specimens suggesting that other events are required for tumorigenesis.
Adenocarcinoma↗
2-Chloroadenosine decreases tyrosylprotein sulfotransferase activity in the Golgi apparatus in PC12 cells. Evidence for a novel receptor.
In the present studies, we investigated the activity of tyrosylprotein sulfotransferase (TPST) in the Golgi apparatus of PC12 cells and the regulation of this enzyme by 2-chloroadenosine, an adenosine receptor agonist. Studies employing continuous sucrose gradient and trypsinization of the membranes demonstrate that TPST is located on the luminal side of Golgi apparatus in PC12 cells. Treatment of PC12 cells with 2-chloroadenosine results in a dose-dependent decrease of TPST activity which is observable as early as 3 h after initiation of treatment, maximizes at 24-48 h with continuous exposure, and is readily reversible upon removal of the drug. While forskolin, an agent that directly increases intracellular cAMP, has no effect on TPST activity, 2-chloroadenosine equally suppressed the enzyme activity in both the wild type and a protein kinase A-deficient mutant strain of PC12 cells, indicating that such regulation of TPST activity by 2-chloroadenosine was independent of cAMP-dependent protein phosphorylation. This effect of 2-chloroadenosine can be potentiated by an adenosine uptake blocker dipyridamole but cannot be elicited by other adenosine A1 or A2 receptor agonists, further suggesting that TPST activity in PC12 cells is regulated by 2-chloroadenosine via a novel membrane receptor. Incubation of the cells with cyclo heximide, a protein synthesis inhibitor, also led to a time- and dose-dependent suppression of TPST activity. At concentrations of cycloheximide that produced maximal inhibition (approximately 50%), cotreatment with 2-chloroadenosine did not lead to a further decrease of the TPST activity. These results suggest that the sensitivity of TPST activity to be controlled by protein synthesis provides a mechanism for regulation of its activity by 2-chloroadenosine.
2-Chloroadenosine↗
Clinical and immunomodulatory effects of combination immunotherapy with low-dose interleukin 2 and tumor necrosis factor alpha in patients with advanced non-small cell lung cancer: a phase I trial.
Sixteen patients with metastatic non-small cell lung cancer were treated with a combination of simultaneous low-dose interleukin 2 (IL-2) and tumor necrosis factor alpha. The purpose of this phase I dose escalation trial was to assess the clinical toxicities, immunomodulatory effects, and antitumor efficacy of this combination. Patients received a continuous daily i.v. infusion of 6 x 10(6) IU/m2 of IL-2 for 5 days and a concomitant daily i.m. dose of tumor necrosis factor alpha on each day of IL-2 administration. Tumor necrosis factor alpha administration started at a dose of 25 micrograms/m2/day (level I) for seven patients, 50 micrograms/m2/day (level II) for seven patients, and 100 micrograms/m2/day (level III) for two patients. Treatment was given at 3-week intervals. Only one patient required monitoring by an intensive care unit during therapy. Major toxic effects included fever, local skin reaction at the i.m. injection site, pancytopenia, and general malaise, all of which were reversible within 48 h of cessation of therapy. Dose level II was determined to be the maximum tolerated dose, with the dose-limiting toxicity being thrombocytopenia (less than 50,000/microliters). In 12 evaluable patients, one partial and three minor tumor regressions were observed. Seven patients with progressive disease before entry into this study had radiographic stabilization of their disease (median, 12 weeks) before termination of therapy due to progression. All patients exhibited biological responses including augmented lymphokine-activated killer and natural killer cell activities while receiving therapy, as assessed by the cytolysis of Raji- and K562 targets in vitro. Enhanced lysis of autologous tumor during therapy was demonstrated for four patients with available tumor samples. Serum levels of IL-2 were detected by enzyme-linked immunosorbent assay 2 weeks after cessation of therapy. This serum IL-2 had biological activity, which was evident from the ability to induce proliferation of NK-8 cells (an IL-2-dependent cell line) which was abrogated by anti-IL-2 antibody.
Adolescent↗
Short rib syndrome Beemer-Langer type with polydactyly: a multiple congenital anomalies syndrome.
A male fetus with short rib (polydactyly) syndrome, Beemer-Langer type was aborted at 30 weeks' gestation because of abnormalities visualized on sonography. This is the first documented case with polydactyly in this recently defined entity. The clinical, radiological, and pathological findings, especially of the bones, are described. The differential diagnosis of this entity is discussed.
Adult↗
Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA.
A human lung cancer cell line (H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a 2-kilobase genomic segment of the K-ras protooncogene in antisense orientation. Translation of the mutated K-ras mRNA in H460a cells was specifically inhibited, whereas expression of H-ras and N-ras was unchanged. A 3-fold growth inhibition occurred in H460a cells when expression of the mutated ras p21 protein was down-regulated by antisense RNA. However, cells remained viable despite the absence of K-ras expression. The growth of H460a tumors in nu/nu mice was substantially reduced by expressed K-ras antisense RNA.
Animals↗
Efficacy of pulmonary metastasectomy for recurrent soft tissue sarcoma.
To evaluate surgical results of resection of second (recurrent) pulmonary metastases from adult soft tissue sarcoma, the survival of 39 patients was analyzed retrospectively. With the exclusion of two patients (one with interval metastases between staged resections and one without histologically proved metastases), three patients were found to have unresectable disease (median survival, 7 months). A significantly (P = 0.0001) longer median survival (28 months) was found for 34 patients whose recurrent metastases were completely resected. The only other factor predicting significantly longer post-thoracotomy survival was resection of a solitary metastatic nodule (median survival, 65 months). Patients who had two or more recurrent nodules resected had a median survival of 14 months only (P = 0.01). Although trends toward longer survival were noted for other prognostic factors, none reached statistical significance. We conclude that the complete resection of a solitary second (recurrent) pulmonary metastatic nodule from adult soft tissue sarcoma predicts long-term survival.
Adolescent↗
[Surgical indications in small cell bronchial cancer].
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Carcinoma, Bronchogenic↗
Thoracic surgery training: it is time for a change.
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Internship and Residency↗
Response to chemotherapy does not predict survival after resection of sarcomatous pulmonary metastases.
Between 1979 and 1988, 26 patients with pulmonary metastases from adult soft-tissue sarcomas were treated with Adriamycin (doxorubicin hydrochloride), Cytoxan (cyclophosphamide), and DTIC before metastasectomy. Thirty-eight thoracotomies were performed with postoperative complications in 5 patients (5/38, 13.2%) and one postoperative death (1/38, 2.6%). Two patients had benign lesions at thoracotomy and were excluded from further survival analysis. The median survival of the remaining 24 patients after thoracotomy was 18.5 +/- 5.9 months, and the actuarial 5-year survival was 22%. Five patients (5/24, 21%) achieved a clinically complete response with preoperative chemotherapy, but all had recurrence in the lung and underwent resection of pulmonary metastases. Seven patients (7/24, 29%) achieved a partial response and had residual disease resected at thoracotomy. Twelve patients (12/24, 50%) showed either no change or disease progression while receiving chemotherapy and were referred for resection. Postthoracotomy disease-free survival and postthoracotomy overall survival did not differ significantly between the three groups. One patient in the group showing no change or progression of disease while receiving chemotherapy is alive without recurrence 57 months after initial pulmonary metastasectomy. Chemotherapy can be used for the initial treatment of pulmonary metastases from adult soft-tissue sarcomas. However, survival after resection of pulmonary metastases cannot be accurately predicted based on the clinical response to preoperative chemotherapy.
Adolescent↗
Reoperative pulmonary resection in patients with metastatic soft tissue sarcoma.
Resection of pulmonary metastases from soft tissue sarcoma has been shown to be associated with a 3-year survival of 25% to 30%. The role of multiple resections for recurrent pulmonary metastases, however, has not been clearly defined. Since 1976, 43 patients have had two or more thoracic explorations for the purpose of resecting pulmonary metastases from adult soft tissue sarcoma at our institution. In 89 reexplorations, through either median sternotomy or lateral thoracotomy, the operative mortality was 0%, and 31 of the 43 patients (72%) could be rendered free of disease at the second thoracotomy. Median survival from the second thoracotomy for the patients with resectable disease was 25 months, whereas median survival of patients who had unresectable disease was 10 months. A disease-free interval between the first and second thoracotomies of greater than 18 months was associated with prolonged survival from the second thoracotomy. Owing to lack of other therapies with proven salvage efficacy and in the absence of randomized trials, repeated thoracotomies to render patients free of disease from pulmonary soft-tissue sarcoma metastases appear justified considering the potential survival benefit and low attendant risk.
Adolescent↗
Improved survival after resection of pulmonary metastases from malignant melanoma.
The value of resecting pulmonary metastases from malignant melanoma was retrospectively examined. Between 1981 and 1989, 56 patients (35 men and 21 women with a mean age of 49 years) had 65 pulmonary resections for histologically proven metastatic melanoma after treatment of the primary tumor. In patients undergoing thoracotomy, 50% (28/56) had pulmonary metastases as the initial site of recurrence. Twenty-eight patients (50%) had local-regional recurrence before the development of lung metastases. Eight lobectomies, two segmentectomies, and 55 wedge excisions were done. Fifty-four patients (54/56, 96%) underwent complete resection, and there were no operative deaths. The postthoracotomy actuarial survival was 25% at 5 years (median interval, 18 months). Location of the primary tumor, histology, thickness, Clark level, local-regional lymph node metastases, or type of resection was not associated with improved survival. Patients without regional nodal metastases before thoracotomy had a median survival of 30 months compared with 16 months for all others (p = 0.04). Patients with lung as the site of first recurrence had a median survival of 30 months compared with 17 months for patients with initial local-regional recurrence (p = 0.038, log-rank test). Despite systemic spread, patients with isolated pulmonary metastases from melanoma may benefit from metastasectomy.
Female↗
Activation of bovine neutrophils by recombinant bovine tumor necrosis factor-alpha.
The in vitro effect of bovine recombinant tumor necrosis factor-alpha (rbTNF-alpha) on bovine neutrophil function and the possibility that rbTNF-alpha and recombinant bovine interferon-gamma (rbIFN-gamma) act synergistically were investigated. Treatment of neutrophils with rbTNF-alpha (0.05 micrograms/ml; approximately 50 U/ml) at 37 degrees C for 2.5 h resulted in enhancement of antibody independent neutrophil-mediated cytotoxicity (AINC) and inhibition of random migration and chemotaxis. The same treatment resulted in a slight decrease in iodination and cytochrome C reduction, but did not affect Staphylococcus aureus ingestion, or antibody dependent cell-mediated cytotoxicity. Kinetic and inhibitor studies indicated that the action of rbTNF-alpha was rapid and was independent of protein and RNA synthesis by neutrophils. Evaluation of the synergistic activities of rbTNF-alpha and rbIFN-gamma indicated that treatment of neutrophils with these two cytokines simultaneously resulted in additive enhancement of AINC and inhibition of random migration and chemotaxis. There was no additive effect of the two cytokines on inhibition of iodination or cytochrome C reduction.
Animals↗
Comparison of the response of bovine and human neutrophils to various stimuli.
Elastase release, oxidant production and cytoplasmic Ca2+ fluxes by bovine and human neutrophils were compared using sensitive kinetic assays on a photon-counting spectrofluorometer. The stimulants used were phorbol myristate acetate (PMA), cytochalasin B, zymosan opsonized with bovine complement (bOZ) or human complement (hOZ), calcium ionophore, formyl-methionyl-leucyl-phenylalanine (FMLP) and concanavalin A (Con A). The respiratory burst of bovine and human neutrophils was stimulated by PMA and OZ but not by cytochalasin B, or calcium ionophore. Con A weakly stimulated this response in human neutrophils but not bovine. FMLP stimulated the respiratory burst of human but not bovine neutrophils. For evaluation of elastase release, human neutrophils were pretreated with cytochalasin B for 5 min and then stimulated. Cytochalasin B alone did not stimulate elastase release from human neutrophils. Phorbol myristate acetate, calcium ionophore, hOZ, FMLP and Con A did stimulate human neutrophils pretreated with cytochalasin B to release elastase. Human serum OZ was also able to stimulate elastase release from human neutrophils not pretreated with cytochalasin B. Some bovine neutrophils released elastase in response to cytochalasin B alone. Those bovine neutrophils that did not release elastase in response to cytochalasin B alone released elastase when stimulated with Con A or calcium ionophore after cytochalasin B pretreatment. Bovine neutrophils did not release elastase in response to FMLP or PMA with or without cytochalasin B pretreatment, but did release elastase in response to bOZ alone. Total elastase activity of bovine neutrophils was determined to be about 50 times less than that of human neutrophils. Intracellular calcium fluxes were stimulated in human neutrophils by calcium ionophore, FMLP, hOZ and Con A but not by PMA or cytochalasin B. Bovine neutrophil calcium fluxes were stimulated by calcium ionophore, Con A and bOZ; cytochalasin B also stimulated bovine neutrophils to increase cytoplasmic calcium concentration. Cytoplasmic calcium fluxes were not stimulated in bovine neutrophils by PMA or FMLP. In summary, human and bovine neutrophils respond similarly to calcium ionophore and OZ, but differently to PMA, cytochalasin B, Con A and FMLP.
Animals↗