Marrow transplantation for Hodgkin's disease: points to ponder.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
M Beer
Publications and source records attributed to M Beer.
[Incidental endoscopic finding--ileum carcinoid. Treatment strategy and prognostic factors].
The malignancy of gastro-intestinal carcinoids is dependent on localisation and size of the tumor. Tumors of the small bowel seem to have a tissue infiltration depth and extension independent of the primary tumor size. We give a case report of a patient with a carcinoid tumor in the terminal ileum with a diameter of 5 mm and a tissue infiltration depth to submucosa. Based on the immunohistochemical investigation of lymphnode metastases for little, accidentally found carcinoids in the ileum a hemicolectomy with wide mesenteric lymph resection is necessary.
Biomarkers, Tumor↗
Role of T-helper-cell subtypes and cytokines in immunity to Yersinia enterocolitica in susceptible and resistant strains of mice.
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Animals↗
Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase.
Microsomal arylacetamide deacetylase (DAC) competes against the activity of cytosolic arylamine N-acetyltransferase, which catalyzes one of the initial biotransformation pathways for arylamine and heterocyclic amine carcinogens in many species and tissues. Activity determination and immunoblot analysis of DAC in human target tissues for arylamine carcinogens revealed that in extrahepatic tissues, additional enzymes are responsible for any deacetylation activity, whereas a single enzyme predominantly catalyzes this hydrolytic reaction in liver. We isolated and characterized a full-length cDNA from a human liver lambda gt11 library. This clone encodes an open reading frame of 400 amino acids with a deduced molecular mass of 45.7 kDa and contains two putative glycosylation sites. The 3'-untranslated region contains two putative polyadenylation signals. The cDNA was confirmed to be that for DAC in tryptic peptides from the purified human liver protein. Highest sequence similarity of DAC was found in a series of prokaryotic esterases encompassing the putative active site. Two extended regions of significant sequence homology with hormone-sensitive lipase and with lipase 2 from Moraxella TA144 were identified, whereas similarity to carboxyl esterases was restricted to the region encompassing the putative active site, indicating that DAC should be classified as esterase. This cDNA provides an important tool to study deacetylation and its effects on the metabolic activation of arylamine and heterocyclic amine carcinogens.
2-Acetylaminofluorene↗
A comparative study of cisplatin and vinblastine versus ifosfamide, cisplatin and vinblastine in non-operable non-small-cell lung cancer. A study of the Hellenic Co-operative Oncology Group for Lung Cancer Trials.
PURPOSE: To evaluate the efficacy and toxicity of ifosfamide in combination with cisplatin and vinblastine in non-operable non-small-cell lung cancer (NSCLC). METHODS: A total of 136 patients with stage III or IV NSCLC were randomized to either PV (cisplatin, 120 mg/m2, and vinblastine, 6 mg/m2) or VIP (PV with the addition of ifosfamide, 3 g/m2) every 3 weeks. RESULTS: Patients receiving VIP had a higher response rate (31% vs. 10%), but the performance status (PS) was significantly worse in those receiving PV. No difference in survival can be demonstrated between the two treatment groups. The median survival was 8.4 months. In both groups, patients with stage III disease, good PS and no visceral involvement had better survivals. Nausea/vomiting and alopecia were more pronounced in the VIP group, although both chemotherapies were well tolerated. CONCLUSIONS: The addition of ifosfamide improved the response rate, but a survival advantage cannot be proven. The prognostic value of stage, PS and metastatic site is confirmed in this trial; further studies are required to select subgroups of patients who may have a survival benefit with combination chemotherapy. The response rate elicited by VIP makes it a candidate for neoadjuvant treatment.
Adult↗
Immune responses to Yersinia enterocolitica in susceptible BALB/c and resistant C57BL/6 mice: an essential role for gamma interferon.
Susceptibility of mice to infection with Yersinia enterocolitica has been shown to be related to neither the Ity locus encoding for resistance to Salmonella typhimurium and other pathogens nor the H-2 locus. Recent studies in our laboratory have demonstrated that T-cell-mediated immune responses are required for overcoming primary Yersinia infection. In the present study, we investigated the course of infection with Y. enterocolitica and the resulting immune responses in Yersinia-susceptible BALB/c and Yersinia-resistant C57BL/6 mice. In the early phase of infection, the clearance of the pathogen was comparable in both strains of mice, suggesting similar mechanisms of innate resistance. Splenic T cells from Yersinia-infected C57BL/6 mice exhibited marked proliferative responses and produced gamma interferon (IFN-gamma) upon exposure to heat-killed yersiniae. By contrast, the Yersinia-specific T-cell response in BALB/c mice was weak, and IFN-gamma production could not be detected before day 21 postinfection. T cells isolated from C57BL/6 mice 7 days after infection mediated immunity to Y. enterocolitica but those from BALB/c mice did not, while at 21 days postinfection T cells from both strains mediated protection. Neutralization of IFN-gamma abrogated resistance to yersiniae in C57BL/6 mice but to a far smaller extent in BALB/c mice. Administration of recombinant IFN-gamma or anti-interleukin-4 antibodies rendered BALB/c mice resistant to yersiniae, whereas this treatment did not significantly affect the course of the infection in C57BL/6 mice. These results indicate that the cellular immune response, in particular the production of IFN-gamma by Yersinia-specific T cells, is associated with resistance of mice to Y. enterocolitica.
Animals↗
A new indole from Penicillium daleae.
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Alkylation↗
Peripheral blood mononuclear mobilization with sargramostim (GM-CSF).
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Adult↗
TMJ: a well-tolerated high-dose regimen for the adjuvant chemotherapy of high risk breast cancer.
Following local treatment and doxorubicin-containing standard chemotherapy, 42 patients with surgical Stage II or IIIA breast cancer containing ten or more involved axillary nodes and 13 patients with Stage IIIB disease were treated with high-dose chemotherapy (TMJ) consisting of thiotepa (750 mg/m2), mitoxantrone (40 mg/m2), and carboplatin (1000 mg/m2), with autologous bone marrow (ABM) and peripheral stem cell (PSC) transplant, followed by irradiation and/or hormone therapy. Sargramostim (GM-CSF) support was given to most patients. The median time to transfusion independence was two weeks. Severe non-hematologic toxicity was uncommon, with no intensive care admission or treatment-related death. At a median follow-up of 17 months, eight patients have relapsed and five have died of tumor progression. No statement can yet be made regarding adjuvant efficacy, but this high-dose regimen is very well tolerated.
Adult↗
[Intraoperative electron irradiation (IORT) of urologic tumors. Initial results of a pilot study of local recurrences of renal cell cancers].
The efficacy of radiotherapy of renal cell carcinomas is limited by its side effects. To avoid gastrointestinal problems the dose must not exceed 45 Gy, but with corresponding protocols no effect has been seen in curative and adjuvant trials. A new three-step protocol combining surgery with intraoperative radiotherapy focussed on the tumor bed fading out the intestine (IORT) and external boost radiotherapy (40 Gy) was used in six patients with local recurrences after tumor nephrectomy. No increase in morbidity was induced by IORT. One year after radiotherapy no recurrences have been seen in the radiation field. We recommend this protocol for patients with solitary local recurrences and for tumors of clinical stage T3 and T4.
Adult↗
[BCG vs interferon A for prevention of recurrence of superficial bladder cancer. A prospective randomized study].
A total of 78 patients with superficial bladder carcinoma were prospectively randomized to two groups following complete transurethral resection (TUR). Each received 12 intravesical instillations of 10(7) units interferon A or 120 mg BCG Connaught for 1 year starting 6 weeks post-TUR. After a mean observation period of 24 (13-31) months in the BCG and 25 (6-32) months in the IFN group 5/32 (15.6%) recurrences in the BCG versus 21/35 (60%) in the IFN group were observed (P = 0.0003). In the IFN group 18.4% of the patients had dysuria and 2.6% fever; in the BCG group 35% had fever, 60% cystitis, 1 patient granulomatous epididimoorchitis and 1 patient pneumonitis with granulomatous prostatitis. With our instillation regimen interferon A had few side effects but also no prophylactic effect, whereas BCG had tolerable-seldom severe--side effects and was very effective in preventing recurrences. Perhaps IFN should be given earlier after TUR and in a higher dosage.
Administration, Intravesical↗
A phase II trial of carboplatin and vindesine in patients with non-small cell lung cancer. A Hellenic Cooperative Oncology Group study.
In an effort to investigate a regimen less toxic and more convenient than cisplatin combinations, 50 patients with non-small cell lung cancer (NSCLC) were treated in a Phase II study with carboplatin and vindesine. Carboplatin 300 mg/m2 every 28 days and vindesine 3 mg/m2 every 2 weeks were administered on an outpatient basis. Eight patients had a partial response of their disease (16%, confidence limits 7-29%). Mean duration of response was 4.5+ months (1 +/- 8). Toxicity, mainly of grade I-II, was noticed in 4-28% of the patients. The most common side effect was mild to moderate leukopenia (28%). The combination of carboplatin and vindesine at the above doses was very well tolerated. Although the response rate was relatively low, the survival in this patient population was similar to other cisplatin-containing regimens.
Aged↗
The cellular immune response against Yersinia enterocolitica in different inbred strains of mice: evidence for an important role of T lymphocytes.
Resistance of mice against infection with Yersinia enterocolitica has been shown to be related neither to the Ity locus coding for resistance against infection with Salmonella typhimurium and other pathogens nor to the H-2 locus. From other mouse infection models, e.g., murine leishmaniasis, there is evidence that a different T cell-dependent regulation of the host immune response in various inbred strains of mice determines the susceptibility to the infectious agent. However, until recently, little was known about the cellular immune response against Y. enterocolitica. Thus, in a first approach we used the highly virulent Y. enterocolitica strain WA of serotype O:8 and different inbred strains of mice (C57 BL/6, Balb/c and athymic T cell-deficient C57 BL/6 nude mice) to investigate the cell-mediated immunity against parenteral infection. Comparison of the median lethal dose and of the net-bacterial growth in the spleens of infected mice indicated that Balb/c mice could be considered as Yersinia-susceptible whereas C57 BL/6 mice were relatively resistant. However, in contrast to normal C57 BL/6, athymic T cell-deficient C57 BL/6 nude mice have proved to be highly susceptible to Yersinia infection suggesting that T cells are required for the elimination of the pathogen. This conclusion was supported by histomorphological and immunohistological results indicating that T lymphocytes were present in Yersinia-induced tissue lesions. Moreover, the adoptive transfer of Yersinia-specific T cell lines and clones into naive animals mediated significant protection against the pathogen in both Yersinia-resistant C57 BL/6 and in Yersinia-susceptible Balb/c mice. These findings emphasize an important role of T lymphocytes in the host response against Y. enterocolitica infection.
Animals↗
Megestrol acetate in cancer patients with anorexia and weight loss. A Hellenic Co-operative Oncology Group (HeCOG) study.
Fifty-two patients with hormone-independent cancer, who complained of anorexia and of weight loss with at least 10%, received megestrol acetate (MA), 480 mg daily, during 1-21 weeks. Of the 41 patients treated during 4 weeks or longer, 38 experienced weight gain. Monthly subjective evaluation of six parameters using a linear analog self-assessment (LASA) form showed a significant improvement in the patient's rating of appetite, mood, nausea and vomiting, and quality of life; the tumor was progressive in 21, stable in 11 and it regressed in only 9 of these patients. No toxicity was observed; one case of death due to a congestive heart failure remains unexplained. MA at the dose used is a powerful appetite stimulant; it contributes to weight increase and might improve the subjective appreciation of quality of life. MA at lower doses should be compared in a prospective trial to the dose used in this study.
Adult↗
[Effect of intraoperative fibrin gluing on lymph flow and lymphocele formation after kidney transplantation].
In a randomized prospective study we examined 100 renal transplant patients including 20 children, to test the hypothesis that intraoperative application of clotting factors (in the form of fibrin glue) reduces the postoperative lymph flow and the frequency of lymphocele formation. The study showed that the use of fibrin glue during renal transplantation did not reduce the postoperative production of drainage fluid or lymphocele formation. The postoperative lymph flow was not related to the formation of lymphoceles. In adults the use of higher doses of immunosuppressants seems to increase the risk of lymphocele formation. On the other hand children have a very low rate of lymphocele formation even when high doses of immunosuppressants are used. The postoperative lymph has a constant composition of erythrocytes and leucocytes. The plasma protein extravasation decreased postoperatively and was influenced by the plasma protein content. From these results we conclude that the postoperative frequency of lymphocele formation cannot be reduced by intraoperative use of fibrin glue in the chosen protocol.
Adolescent↗
Novel 5-HT3 antagonists: indol-3-ylspiro(azabicycloalkane-3,5'(4'H)-oxazoles).
The synthesis and biochemical evaluation of a series of spirofused indole oxazoline 5-HT3 antagonists is described in which the oxazoline ring acts as a bioisosteric replacement for esters and amides. The effect of substitution about the indole ring has shown the steric limitations of the aromatic binding site. Incorporation of a variety of azabicyclic systems within the rigid spirofused framework has allowed the definition of a binding model which incorporates a number of known antagonists and agonists. In this model steric constraints limit substitution around the indole ring although there is some bulk tolerance at the 1- and 2-positions. The importance of constraining the basic nitrogen within an azabicyclic system is underlined by comparison with the monocyclic piperidine. The highest affinity was observed for those compounds in which the basic nitrogen occupies a bridgehead position, the most potent analogue in this group being the azabicyclic [3.3.1] system (pIC50 = 8.95), suggesting lipophilic interactions may play a role in increasing affinity. A suggested model for agonist binding is included in which the basic nitrogens are superimposed and the 5-hydroxyl group of 5-HT is superimposed on the H-bond-accepting atom of the heterocyclic linking group.
Animals↗
A randomized prospective study of cisplatin and vinblastine versus cisplatin, vinblastine and mitomycin in advanced non-small cell lung cancer.
From June 1986 to February 1989, 103 patients with advanced non-small cell lung cancer, with no previous chemotherapy, were randomized to receive either a combination of cisplatin and vinblastine (group A) or the same combination with the addition of mitomycin (group B). In group A, 15/48 evaluable patients had objective responses, as did 8/45 in group B. The median survivals were 35 and 32 weeks, respectively. The median survival of patients with response or stable disease was 43 weeks. Response and survival did not differ significantly between treatment groups. The addition of mitomycin to the two-drug combination showed no major therapeutic benefit, while bone marrow toxicity was increased. Three patients in group B died of sepsis. Among the different patient characteristics, disease stage, performance status and response had influence on survival.
Adult↗
Factors influencing complete response and survival in patients with head and neck cancer treated with platinum-based induction chemotherapy. A Hellenic Co-operative Oncology Group Study.
One hundred fifteen consecutive patients with locally advanced carcinoma of the head and neck were treated between August 1984 and August 1989 with three cycles of either of two platinum-based induction chemotherapies, followed by local treatment. After the completion of chemotherapy 26 (23%) patients had complete responses (CR). Several pre-treatment characteristics were analyzed for a possible correlation to CR to induction chemotherapy and to survival. The following variables were closely interrelated: sex, history of smoking, alcohol abuse, histologic type, tumor site and grade. Tumor stage and negative history of smoking were correlated with CR. The variables which were individually correlated with survival were keratinization, CR to chemotherapy, alcohol abuse, histologic type, site and grade of the primary tumor, serum albumin level and tumor stage. A regression analysis after Cox's model to identify a limited set of predictors selected CR, serum albumin, tumor grade, performance status and nodal status as the most significant; when analyzing the data without the time-dependent variable CR, the factors selected by the model were serum albumin, tumor grade, performance status and tumor stage. In conclusion, serum albumin level, tumor grade, performance status and tumor stage prior to treatment can be used to define risk classes in our patient population.
Adolescent↗