Discoloration of the nails and early anemia after mitoxantrone, folinic acid and 5-fluorouracil.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to P Seminara.
Explore the source record for details and available documents.
Five patients with oligoarticular rheumatoid arthritis were treated with intra-articular injections of methotrexate and orgotein in the knee joints. The employed dose of the antimetabolite was very low and orgotein was simultaneously administered to prevent local tissues from cytolysis-related damage. Clinical results were fairly good and support the hypothesis that methotrexate may be used intra-articularly as an immunosuppressor rather than at the heavily toxic doses required for a cytostatic effect.
A short-term antimetabolic assay, which considers the interference with [3H]thymidine incorporation as an indicator of drug effect, has been used to comparatively assess the chemosensitivity of different tumor lesions from the same patient. The analysis was performed on primary tumors and their synchronous metastases from 67 patients with breast, ovarian, gastrointestinal and germ cell testicular tumors. A remarkable difference in sensitivity to cytostatic drugs was observed between the two lesions. In contrast, a strong association in chemosensitivity (81.7% agreement rate; p less than 0.01) was observed between two synchronous metastases from 17 patients with breast, ovarian, germ cell testicular tumors or malignant melanoma. In addition, the predictive relevance of the antimetabolic assay on clinical response to chemotherapy was analyzed in relation to the type of tumor lesion tested in vitro in a retrospective correlative study on 57 patients with advanced ovarian and germ cell testicular tumors. The objective clinical response was significantly correlated to the in vitro sensitivity of metastases (83.7% agreement rate; p less than 0.01), but not to that of the primary tumor.
Explore the source record for details and available documents.
The chemosensitivity of 26 non-pretreated colorectal carcinomas (primary tumors and/or colorectal metastases) was studied by an in vitro antimetabolic assay, which evaluates the interference of drugs on the incorporation of 3H-thymidine and 3H-uridine in short-term cultures of human tumors. Our results correlate with the response rate obtained in clinical studies with monochemotherapy and justify the possibility of a future prospective study using individually tailored chemotherapy regimens. Doxorubicin-analogues, with an overall in vitro efficacy in 16.0% and 14.3% for 4-epidoxorubicin (epi-DX) and 4-deoxydoxorubicin (deo-DX), respectively, seem to deserve a modest role in the treatment of colorectal cancer, provided that a careful selection of patients is performed. Variability in anthracycline activity is indeed evident, also in our study, in relation to the different neoplastic picture of the various patients.
A case of prolymphocytic leukemia (PL) is reported, which showed a good response to a new antiblastic schedule (4-epidoxorubicin-asparaginase-dexamethasone) in spite of the resistance to other chemotherapy regimens. However during the course of the disease it was possible to observe the terminal appearance of a small aneuploid cell population in the peripheral blood of the patient and, in the same time, the clinical condition deteriorated considerably. The significance of this neoplastic progression and the pros and cons of aggressive chemotherapy regimens remain to be carefully evaluated in PL and related disorders.
A case of non-producer multiple myeloma (MM) is described and compared with the previous reports. Some recurrent clinical traits seem to characterize this disease. It is interesting that reported cases seem to show a low aggressivity. Some biological problems connected with this form of disease are discussed.
A case is presented of an aneurysm arising from the distal portion of the medial branch of the superior cerebellar artery. The aneurysm was discovered after a subarachnoid hemorrhage and was clipped successfully. We found no similar distally located aneurysm in a review of the literature. The close relationship between the superior cerebellar artery and the posterior cerebral artery is discussed to facilitate the proper choice of surgical approach.
A brief survey of the problems related to leukemic cell differentiation is proposed. The role of cytosine-arabinoside among the differentiation inducers and its potential clinical utility is discussed on the basis of the present literature. The authors report a case of myelomonocytic leukemia which displayed a differentiative response to cytarabine treatment.
Explore the source record for details and available documents.
A case of chronic neutrophilic leukemia associated with multiple myeloma is described. The patient appears to be the longest surviving case reported in the literature. Since myeloma developed several years after leukemia, the possible precancerous role of myeloproliferative syndromes is proposed.
The 4th case of plasma cell neoplasm associated with a hypereosinophilic syndrome is described and compared with the previous reports. Hypereosinophilia in the present patient displayed some borderline traits with eosinophilic leukemia. Myeloproliferative disorders of the eosinophilic line often present as a precancerous state, but sometimes they seem to acquire malignant independence. In our patient the occurrence of a plasmocytoma with a dramatic course leads to suspect an underlying complex genetic aberration.
Three cases of primary cutaneous T-cell lymphoma non-Sézary and non-mycosis fungoides are described, in which ultrastructural investigations revealed the presence of interdigitating reticulum cell in the skin infiltrate. The cytological finding is discussed in light of the immunological function hypothetically performed by the skin.
Explore the source record for details and available documents.
Data on lymphocyte biology indicate that the humoral system of B-cells is specifically active with precise analogies at all mucosal levels. Might there be a corresponding function for T-lymphocytes at the cutaneous structure level? Certain physiological findings appear to suggest that the two main lymphocyte populations share the role of "first defence barrier".
We evaluated the activity of ruboxyl (Rbx), a nitroxyl analogue of daunorubicin (Dauno), in experimental models of hepatic metastases from colorectal carcinoma (CRC) and compared it with its parent compound and with 5-fluorouracil (5FU). In mice treated by intraperitoneal injections Rbx and 5FU proved more effective than Dauno: the Index of Inhibition of Metastases in comparison with controls was 43% for Dauno, 70% for 5FU and 84% for Rbx. In BDIX rats implanted with the syngeneic cell line DHD K12/TRb, both Rbx and 5FU, administered as a continuous intravenous infusion for 7 days, reduced the development of liver metastases from a median of 23.8 +/- 2.16 for controls to 3.2 +/- 1.3 for 5FU and 1.0 +/- 1.4 for Rbx (p < 0.0001 versus controls for both treatments): the comparison of Rbx and 5FU showed a trend in favour of this new anthracycline. Median survival was prolonged from 40.6 +/- 3.4 days in controls to 56.0 +/- 5.8 days with Rbx and 58.0 +/- 4.69 days with 5FU. Considering that in a phase I study Rbx showed only minor and manageable toxic side effect, its activity in the clinical treatment of CRC metastases may deserve further attention.
BACKGROUND: Age-related physiological changes may lead to an increased toxicity of chemotherapy in the elderly, thus making tumor treatment difficult in this increasing subset of patients. OBJECTIVE: Since many trials claimed a favorable therapeutic index with raltitrexed, the aim of our preliminary study was to evaluate the anticancer activity and the toxic profile of this drug in the elderly. METHODS: Thirteen elderly patients with colorectal cancer, aged 75-90 years, were enrolled in a monochemotherapy treatment with raltitrexed. Due to their advanced age, the drug was administered with a 33% reduction of the dose. RESULTS: One partial response, four disease stabilizations, and two disease progressions were observed in 7 patients with advanced colorectal cancer. The patients with response or disease stabilisation had a satisfactory time to progression. Four out of 6 patients treated in the adjuvant setting for Dukes' C colorectal cancer remain disease free at observation periods of 15+ to 29+ months. Toxicity was virtually absent in all patients. CONCLUSIONS: The activity of monochemotherapy with raltitrexed appears to be appealing, above all because it is observed in the absence of toxicity. Though recent reports suggest some concern about severe complications of treatment with raltitrexed, administration of reduced doses of this drug seems to be a putative therapy for those patients who, because of their age, are highly susceptible to the adverse effects of chemotherapy.
AIMS AND BACKGROUND: There is much interest in nitroxyl derivatives of cytotoxic agents. We evaluated the potential activity of magnizil, a derivative of 5-fluorouracil, on human gastrointestinal tumors in 3 different in vitro and in vivo experimental models. METHODS: The activities of magnizil and 5-fluorouracil were comparatively determined in vitro on the HT29 cell line by a clonogenic assay and on tumor clinical specimens by an antimetabolic assay. The activity of both the drugs against human tumors was also assessed in mice with the subrenal capsule assay. RESULTS: A similar cytotoxic activity was found for magnizil and 5-fluorouracil on the HT29 cell line. As regards human tumors, a lower activity was observed for the nitroxyl derivative than for 5-fluorouracil, with response rates of 25% and 50%, respectively, at comparable concentrations. Moreover, among the tumors transplanted in the subrenal capsule of mice, two were sensitive to magnizil and 3 to 5-fluorouracil. CONCLUSIONS: Even though experimental results on human tumors indicate a somewhat lower activity for magnizil than the parent compound, its low toxicity and the possibility to clinically use high doses suggest the opportunity to further investigate the potential of this new anticancer agent on larger series of colorectal cancers in experimental systems.