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Biomedical subjects

R Somers

Publications and source records attributed to R Somers.

At least 109 records · Page 6Linked to original sources

Treatment of two patients with B cell lymphoma with monoclonal anti-idiotype antibodies.

Mouse monoclonal anti-idiotype antibodies have been used to treat two patients with progressive advanced B cell non-Hodgkin's lymphoma. Transient falls in the level of circulating malignant cells and idiotypic immunoglobulin were produced, and free unbound monoclonal antibody was identified in the serum. Homing of the antibodies to tumor cells in the blood, bone marrow, ascites, and lymph nodes was demonstrated in both patients. Although large amounts of anti-idiotype antibody were given (3.8 g and 5.8 g), no toxic effects were seen, and no antibodies to the foreign mouse protein were made. There was no modulation of the antigen from the tumor cells and no indication of immunoselection. There was evidence of large-scale tumor cell destruction, but only a modest reduction in tumor size. The killing of the tumor cells was mediated by the reticuloendothelial system and not by complement.

Aged↗

Prognostic significance of the number of involved areas in the early stages of Hodgkin's disease.

An analysis of 1059 patients with clinical stage (CS) I and II Hodgkin's disease was undertaken to determine the prognostic significance of the number of involved sites. In this group of patients the number of involved lymph node areas was highly correlated with the probability of dissemination of occult disease. In the subgroup of patients with involvement of two lymph node sites (CS II2) approximately 50% demonstrated occult dissemination on the other side of the diaphragm as evidenced by subsequent relapse in the untreated subdiaphragmatic region. However, only 15% to 20% of this group had unsuspected disease in regions other than the spleen or the paraaortic lymph nodes. In CS I and II2 supradiaphragmatic patients, who underwent a staging laparotomy, splenic involvement was a powerful prognostic indicator. When the spleen was not involved, less than 10% of patients had disease elsewhere below the diaphragm, whereas, when the spleen was involved as many as 40% of patients had additional subdiaphragmatic sites involved. In the subgroup with three or more lymph node areas involved (CS II3), the proportion of patients with extension of disease on the other side of the diaphragm, as evidenced by later relapse was also about 50%. But in these patients, unlike the CS II2 patients, analysis of relapse patterns showed that occult disease had already disseminated to the pelvic nodes or to extra nodal sites. Furthermore, splenic involvement was of much less prognostic significance because CS II3 patients who did not demonstrate splenic involvement at staging laparotomy had similar relapse incidence and similar relapse patterns as those with positive spleens.

Adult↗

Antibodies against a retinal guanine nucleotide-binding protein cross-react with a single plasma membrane protein in non-retinal tissues.

Antisera (AS/1-AS/6) to purified bovine retinal transducin, a guanine nucleotide-binding protein, were produced in 6 rabbits. Immunoblots showed that the antisera varied in their reactivity with the subunits of transducin; AS/1 reacted strongly with all 3 subunits, while the others reacted with only the beta and/or gamma subunits. Only AS/1 specifically immunoprecipitated the alpha subunit radiolabeled with non-covalently bound guanine nucleotides. Immunostaining of plasma membrane proteins from non-retinal tissues with AS-1 revealed a single protein (approx. 35 kDa), most likely representing the beta subunit of the guanine nucleotide-binding proteins (Gs and Gi) associated with adenylate cyclase. Cerebral cortex showed the highest content of this protein. Antisera against transducin provide a highly specific and sensitive probe for quantitation of the beta subunit of Gs and Gi.

Animals↗

Cyvadic in advanced soft tissue sarcoma: a randomized study comparing two schedules. A study of the EORTC Soft Tissue and Bone Sarcoma Group.

Two hundred forty-six adults with advanced progressive soft tissue sarcoma received combination chemotherapy with cyclophosphamide, vincristine, Adriamycin (doxorubicin), and DTIC. They were randomly allocated to receive the four drugs simultaneously every 4 weeks (S1: CYVADIC), or pairs of drugs (S2: ADIC-CYV) alternating at 4 weekly intervals. One hundred sixty-two patients completed 8 weeks of chemotherapy, and were considered to be evaluable for response. There were 18 complete remissions and 25 partial remissions, an overall response rate of 26%, with a highly significant difference between the two arms in favor of S1 (38% versus 14%, P = 0.001). There were no significant differences between S1 and S2 in terms of median duration of remissions (62 versus 39 weeks), and median survival of responders (85 versus 80 weeks) and of all evaluable patients (43 versus 45 weeks). Karnofsky index (KI) was the single most important prognostic factor. Patients with KI 90-100 showed a remission rate of 41% (56% on the S1 regimen) in contrast with 14% in those with KI 50-80. No patient with a KI of 50 responded to chemotherapy. The main toxicities were nausea, vomiting, anorexia, alopecia and myelosuppression, but did not differ significantly between the two regimens. Our findings suggest that stratification according to KI is essential for studies on chemotherapy for advanced soft tissue sarcomas in order to make a valuable comparison of treatment results.

Adolescent↗

Acute leukemia following therapy for teratoma.

Three cases of acute leukemia are reported following aggressive therapy for inoperable germ cell tumors. Two patients were treated by radiation plus cytotoxic chemotherapy and the third received only drugs. The time between onset of these therapies to death from leukemia was 4, 17 and 61 months.

Acute Disease↗

The EORTC treatment of early stages of Hodgkin's disease: the role of radiotherapy.

Since 1964, the European Organisation for Research and Treatment of Cancer has conducted three subsequent clinical trials on clinical Stages (CS) I + II Hodgkin's disease (HD) in which 1059 patients have been entered. The first trial compared regional radiotherapy (RT) with mantle field or inverted Y, versus the same RT followed by a weekly injection of vinblastine for 2 years. The relapse free survival (RFS) and overall survival (S) were higher in patients treated by RT and chemotherapy (CT). This benefit, however, was significant only in patients with a mixed cellularity histologic type. The second trial compared the therapeutic efficacy of splenic irradiation versus splenectomy and found that in both arms, RFS and S were identical. Moreover, it was found that splenic involvement was correlated with an increased incidence of relapse in extranodal sites and in non irradiated lymphatic areas. In this trial, CT was given only to patients with poor histologic types, mixed cellularity or lymphocytic depletion. In the third trial, staging laparotomy was performed only to further delineate a good prognostic group which could be treated by RT alone. In this limited treatment group, there was no difference in RFS and S between mantle field and mantle field + para-aortic RT. In the extensive treatment group, total nodal irradiation (TNI) was compared with RT + MOPP. The RFS was slightly lower in the TNI arm, but there was no significant difference in S. The data of the 3 trials underline the importance of prognostic factors in the choice of optimal treatment and show that their significance depends upon the type of treatment. Multivariate statistical analyses showed that the main prognostic factors, which can help to identify the subsets of patients who can be treated by RT alone, are (1) systemic symptoms and elevated erythrocyte sedimentation rate (ESR), (2) the number of involved lymphatic areas, and (3) staging laparotomy. Extended RT (mantle + para-aortic + spleen treatment) gives satisfactory results in patients without systemic symptoms and/or elevated ESR and one or two involved sites, whereas TNI or combined modality treatment becomes mandatory for patients with 3 or more involved sites or splenic involvement and/or systemic symptoms. With proper adjustment of the irradiated volume, a very large proportion of CS I + II patients can be best treated by RT alone.

Adolescent↗

Combined radiotherapy-chemotherapy for early stages non-Hodgkin's lymphoma: the 1975-1980 EORTC controlled lymphoma trial.

Patients with stage I and II non-Hodgkin's lymphoma (NHL) are considered to have a relatively good prognosis. For this reason, they are seldom referred to specialized centers and the accrual of such patients in controlled studies is limited. Therefore, significant studies of homogeneously treated patients are difficult to collect and the management of these patients remains controversial. Some patients do very well after treatments with minimal toxicity while others require a much more aggressive approach. The Radiotherapy-Chemotherapy Group of the EORTC carried out its second controlled trial on patients with stage I and II NHL from 1975 to 1980. Its first aim was to assess the prognostic value of histologic classifications independently of treatment. The second aim was to compare two therapeutic options within each stage. In stage I, 124 patients were randomized to receive extended field radiotherapy (RT) either with or without adjuvant cyclophosphamide, vincristine prednisone (CVP) chemotherapy (CT). Relapse-free survival (RFS) was higher in patients who received adjuvant CVP but the total survival rates were not different. The RFS was lower in patients with diffuse than in those with follicular architectural histologies; in the former, RFS was not influenced by adjuvant CVP. Those patients who underwent a staging laparotomy had a higher 5-year total survival (TS) independent of the histologic type. Fifty-six stage II patients were included and extended field was randomized versus total nodal irradiation. Subsequently, adjuvant CVP was given to all patients. Results are good in follicular histologies but the advantage for total nodal irradiation is not significant. In diffuse histologies, results were unsatisfactory in both arms; a new therapeutic strategy was designed in which RT and CT are alternated and has been successfully tested in a pilot study.

Adolescent↗

Sequential non-cross-resistant chemotherapy regimens (MOPP and CAVmP) in Hodgkin's disease stage IIIB and IV.

Fifty consecutive patients with advanced Hodgkin's disease were treated in a multicentre study with 6 cycles of an alternating scheme of MOPP and CAVmP followed by irradiation to a dose of 20 Gy. The objective was to increase complete remission (CR) and cure rates by alternating two effective noncross-resistant regimens with subsequent consolidation of the remission by irradiating bulky nodes. A total of 47 patients completed the treatment and are evaluable. In the first 13 patients the irradiation fields amounted to a total or subtotal nodal irradiation with inclusion of the spleen. In case of organ involvement the affected organ was also included in the irradiation field. The irradiation protocol was later changed to an irradiation of the initially involved sites because of severe leucopenia and thrombopenia. After completion of the chemotherapy 32 (68%) patients (for Stage IIIB and IV patients: 63% and 71%, respectively) achieved a CR, after ending the radiotherapy the percentage of CR increased to 87% (for stage IIIB and IV patients: 90% and 86%, respectively). Five of the patients relapsed in an irradiated and nonirradiated area, three patients in a nonirradiated field. The actuarial 3-year survival rate for the entire group was 86% and for patients in CR 94%. The relapse-free survival was 73%. It is concluded that this alternating chemotherapy scheme followed by irradiation is at least equally effective as MOPP treatment in achieving a CR, and is probably superior in terms of survival.

Adolescent↗

Schiff's base formation in the lens protein gamma-crystallin.

Uniquely among the soluble lens-specific proteins, gamma-crystallin is capable of binding the strongly chromophoric aldehyde retinal. A role for gamma-crystallin in protecting lens components from toxic aldehydes resulting from membrane oxidation is proposed and a molecular model of the probable interaction site is presented. The sequence of a tetrapeptide at this site is identical to that of the retinal binding site of bacteriorhodopsin.

Animals↗

Carminomycin vs adriamycin in advanced soft tissue sarcomas: an EORTC randomised phase II study.

Eighty-three patients with advanced soft tissue sarcoma who had received no prior chemotherapy entered a randomised phase II study comparing carminomycin (CMM) 20 mg/m2 with adriamycin (ADM) 75 mg/m2, both administered i.v. bolus every 3 weeks. Six patients were ineligible and response could not be evaluated in 6 additional patients. Thirty-eight evaluable patients received ADM and 33 received CMM. There was one complete response to ADM and 10 partial responses, an overall response rate of 29%. CMM showed significantly (P = 0.01) lower antitumour activity--one partial response (3%). Stabilisation of disease was similar in both arms (47 and 45%), but fewer patients progressed on ADM (24 compared to 52%). Durations of response dating from the start of chemotherapy were 5 months for complete remission on ADM, a median of 7 months (range 4-17) for partial response on ADM and 14 months for the one partial remission on CMM. Although the median time to progression for all patients receiving CMM (2 months) was significantly (P = 0.001) shorter than for those receiving ADM (5 months), patients on ADM had only a marginally significant longer duration of survival (P = 0.06) than the patients receiving CMM. A leucocyte nadir less than 2.0 X 10(9)/l occurred in 38% of patients receiving ADM and 43% receiving CMM. Anaemia and thrombocytopoenia were uncommon. Other toxicities such as nausea, vomiting, anorexia and alopecia were more severe in the ADM group. There was one infective death secondary to leucopoenia in the ADM arm, and one patient who had received 109 mg/m2 CMM + 255 mg/m2 ADM developed progressively fatal cardiomyopathy.

Adolescent↗

Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma.

Treatment results of leptomeningeal metastasis are reported in 33 breast cancer patients. They were divided into three groups: group 1, 19 patients, received intraventricular methotrexate (MTX) with doses based on CSF MTX levels; group 2, 6 patients, received whole brain radiation followed by a course of MTX given by lumbar punctures; group 3, 8 patients, was not treated. Median survival in group 1 was 6 months; 25% survived 1 year or more. Median survival (1 to 2 months) in groups 2 and 3 was significantly shorter. Neurologic improvement was seen in an average time of 4 weeks in about 80% of group 1 patients. Two of group 2 patients improved at 3 weeks, and all group 3 patients deteriorated. Carcinomatosis caused death significantly less often in group 1 than in the other groups.

Adult↗