An incubation tray to speed up immunostaining.
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Histocytochemistry↗
Biomedical subjects
M Forni
Publications and source records attributed to M Forni.
Preliminary analysis of combined treatment with prednimustine and 4'epidoxorubicin in advanced breast cancer.
In an effort to define a well-tolerated therapeutic regimen for advanced breast cancer, we have studied a combination of 4'epidoxorubicin, 50 mg/m2 IV on day 1, and prednimustine, 100 mg/m2 PO on days 3 to 7 given every 3 weeks. Twenty-nine patients have been entered, and 22 are presently evaluable for response. Median age of the evaluable patients is 62 (range, 36 to 77), and median performance status (SAKK) is 2. Five patients had received chemotherapy, 16 hormonal therapy, five radiation therapy, and five no prior therapy for advanced disease. Most patients were in a high-risk group, with dominant visceral metastatic sites in 19 out of 22 cases. We have observed eight partial responses, nine no changes, and five progressions. Median response duration is 6 months. It is too early to discuss median overall survival. Toxicity is evaluable in 27 patients who received at least one course with a full dose of chemotherapy. Hematologic toxicity has been low, with only four patients having leukocyte nadirs below 2000/mm3 and three patients with thrombocyte nadirs below 100,000/mm3. Major alopecia (requiring a wig) was observed in eight patients. Emesis (controlled by minor antiemetics) was reported in six cases. This well-tolerated regimen is active in advanced high-risk elderly breast cancer patients, but dosage might be too low for younger patients and nonpretreated patients.
Adult↗
B- and T-lymphocytes in Hodgkin's disease. An immunohistochemical study utilizing heterologous and monoclonal antibodies.
Immunohistologic techniques utilizing monoclonal antibodies have made possible the identification of leukocytes by their phenotypic characteristics rather than by morphologic features alone. A panel of antibodies for T-lymphocyte, B-lymphocyte, and monocyte/histiocyte markers has been applied to frozen sections of nodular sclerosing and mixed cellularity Hodgkin's disease to identify more precisely the various cell types present in tissues involved in Hodgkin's disease. The majority of lymphocytes expressed detectable T-cell phenotypic markers, with a predominance of the "helper" phenotype (Leu 3/OKT4) in most cases. Lymphocytes reacting with anti-B-cell antibodies were also demonstrated; their distribution is described here and has not previously been reported. The anti-B- and anti-T-cell antibodies used in this study failed to give positive reactivity with Reed-Sternberg cells. However, one of the anti-monocyte antibodies (Leu-M1) reacted with diagnostic Reed-Sternberg cells in some cases. The patterns of staining observed varied widely within the two histologic types of Hodgkin's disease, leading to a conclusion that this disease may be more heterogeneous than is currently suspected.
Antibodies, Monoclonal↗
Single photon emission computed tomography study of human cancer: utilization of 57Co-labelled bleomycin.
The sensitivity and specificity of single photon emission tomography with 57Co-labelled bleomycin (57Co-BLM) for the detection of cancer was determined from a prospective study involving a large group of patients selected to investigate roentgenographic abnormalities. Eighty-four of the 104 patients studied had malignant disease, of whom 76 had a positive scintigram. Eighteen of the 20 patients with benign disorders had a negative scintigram. The sensitivity and specificity was therefore 90.5 and 90% respectively. For the subset of patients who underwent investigation below the diaphragm, the sensitivity was 85.7%, while for investigation above the diaphragm, it reached 95.2% (this excluded reconstructions on the bladder level, because it produced large artifacts). This study leads to the conclusion that SPECT can be used specifically to investigate unidentified X-ray abnormality and diagnose malignancy using 57Co-BLM. In addition, we propose further investigation to evaluate the usefulness of this method in staging cancer.
Aged↗
SPECT study of the fluid distribution in the intra-abdominal space during intraperitoneal treatment of ovarian cancer.
Only limited progress has been achieved in the treatment of ovarian cancer, the most common fatal gynaecological malignancy. Peritoneal dialysis with drugs known to be effective in ovarian cancer and large intraperitoneal fluid volumes (Belly Bath) have been used. The two critical determinants for a successful intraperitoneal chemotherapy programme are: (1) complete accessibility of the drug to all tumour-bearing areas; and (2) drug penetration into the residual tumour masses. We show that the scintigraphic technique in tomographic mode after administration of MAA-99Tcm-containing dialysate is a valuable adjunct for evaluation of patients undergoing intraperitoneal chemotherapy.
Adenocarcinoma↗
Adriamycin impairs phagocytic function and induces morphologic alterations in human neutrophils.
Normal human polymorphonuclear leukocytes (PMNL) were preincubated in vitro with methotrexate, 5-fluorouracil, vincristine, cisplatin, Adriamycin (doxorubicin), and daunomycin for 15 hours before being tested in a phagocytic-bactericidal assay. Anthracycline-treated PMNL were defective in phagocytosis and killing of the bacteria, in contrast to the other chemotherapeutic agents which allowed the PMNL to remain functional. The defect of Adriamycin-treated PMNL resulted from decreased ingestion: 3 micrograms/ml Adriamycin inhibited by 50% of the uptake of Oil Red-O particles. In this assay, the proportion of noningesting PMNL increased from less than or equal to 20% with 0.62 micrograms/ml to greater than or equal to 90% with 10 micrograms/ml Adriamycin. Electron microscopy revealed that Adriamycin-inactivated PMNL had rounded up, were depleted in glycogen, and had undergone profound nuclear changes. RNA and protein synthesis in PMNL were also affected. Adriamycin, besides producing neutropenia, may decrease the phagocytic function of circulating PMNL.
Antineoplastic Agents↗
Granuloma annulare. Identification of cells in the cutaneous infiltrate by immunoperoxidase techniques.
To characterize the immunopathologic process of granuloma annulare, frozen sections of eight specimens were evaluated with monoclonal antibodies directed against T lymphocytes and the monocyte-macrophage series, in conjunction with immunoperoxidase techniques and with histochemical staining. The predominant lymphocyte was an activated T lymphocyte (Leu 1+, HLA-Dr+) with an excess of helper-inducer phenotype (Leu 3a+), as compared with suppressor-cytotoxic phenotype (Leu 2a+). OKT-6+ Langerhans' cells were observed in the epidermis, and numerous OKT-6+ cells were observed in the perivascular and granulomatous infiltrate. The use of four monoclonal antibodies, having specificity against peripheral blood monocyte antigens, revealed three different staining patterns in the granulomas. Finally, mast cells were present in perivascular and granulomatous infiltrates. Our results demonstrate that the cutaneous infiltrate of granuloma annulare contains all of the principal cell types that characterize cell-mediated immune responses.
Antibodies, Monoclonal↗
Immunoscintigraphy for the detection of human carcinoma after injection of radiolabeled monoclonal anti-carcinoembryonic antigen antibodies.
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Antibodies, Monoclonal↗
An immunohistochemical study of hemoglobin A, hemoglobin F, muramidase, and transferrin in erythroid hyperplasia and neoplasia.
The bone marrow biopsy specimens of 35 patients with benign and malignant erythroid hyperplasias were examined for the presence of hemoglobin A, hemoglobin F, muramidase (lysozyme), and transferrin, using an indirect immunoperoxidase method (PAP) on Zenker's-fixed paraffin-embedded bone marrow biopsy specimens and particles. Five cases of each of the following entities were studied: erythroleukemia and erythremic myelosis, acute granulocytic leukemia with maturation (FAB M2), polycythemia rubra vera, myeloproliferative syndrome in childhood, megaloblastic anemia (B12 and folate deficiency), erythroid hyperplasia (regenerating bone marrow and hemolytic anemia), and Ph' chromosome positive chronic granulocytic leukemia. Hemoglobin A was present in both the early and late erythroid precursors in all conditions. Hemoglobin F was the predominant hemoglobin in early erythroblasts of pernicious anemia and in both early and late erythroid elements in erythroleukemia and erythremic myelosis. Small quantities of hemoglobin F were present in a few isolated clusters in other conditions. Staining for hemoglobin F may be useful in identifying immature erythroid precursors and in distinguishing some cases of dysplastic erythroid hyperplasia from neoplasia. Additionally, these findings suggest that the maturational switch in hemoglobin synthesis operates with distinct pathways under different conditions.
Bone Marrow↗
Immunohistochemical characterization of reactive and neoplastic mast cells.
Mast cells are connective tissue elements likened to unicellular endocrine organs because of the wide diversity of physiologic and pathologic events associated with the secretion of biologically active compounds. Using an immunoperoxidase method (PAP), we studied tissue from patients with benign and malignant systemic mastocytosis and with a variety of reactive conditions. The following immunoreactive antigens were identified in mast cells: a heparinlike compound or compounds (HLC), prostaglandin, serotonin, and fibronectin. HLC is constantly present, staining mast cells in a granular fashion from most lesions. Serotonin and prostaglandin stain in a diffuse cytoplasmic manner in occasional lesions. Fibronectin is found in a surface location in selected cases. We found no clear association between the immunoreactivity of one compound in mast cells and one clinical symptom, e.g., HCL with bleeding, prostaglandin, or serotonin with systemic vasomotor activity or fibronectin with increased tissue fibrosis. However, patients with localized and systemic disease had symptoms that might have been attributed to more than one compound. Only occasional patients with reactive conditions showed such symptoms. The presence of these compounds, either alone or in combination, did not separate benign from malignant conditions. Other cells within selected tissues also stained with the antibodies tested. Despite the lack of exclusivity, these antibodies are useful in identifying mast cells within tissue sections and may have a role in the study of mast cell constituents.
Animals↗
Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma.
A radiolabeled monoclonal antibody (MAb) that has been shown to react specifically in vitro and ex vivo to human colorectal carcinoma and to inhibit growth of human carcinomas grafted in nude mice was administered to 52 colorectal carcinoma patients and 15 patients with other types of cancer. Of 63 colorectal carcinoma tumor sites studied, 34 showed significant accumulation of antibody by external photoscanning and tomoscintigraphy, whereas none of the 20 sites of other cancer types gave positive results. One-third of the patients received F(ab')2 fragments of the MAb, which gave a slightly higher percentage (61%) of positive results than did intact MAbs (51%). A few patients scheduled for tumor resection were given injections simultaneously of 131I-labeled MAb and 125I-labeled normal immunoglobulin G. Antibody concentration in resected tumors was 3.6 to 6.3 times higher than the average antibody concentration in adjacent normal tissues (1.5, 3.4, and 9.4 as compared with normal mucosa, serosa, and fat, respectively), and the specificity indices, calculated by differential radioactivity analysis, ranged from 2.1 to 5.1. The results show the potential value and limitations of this particular MAb for tumor detection by immunoscintigraphy.
Antibodies, Monoclonal↗
[A case of parathyroid hemorrhage with fetal evolution].
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Female↗
[The toxicity/efficacy relationship in polychemotherapy of lung neoplasms].
Although it is generally accepted that anti-cancer chemotherapy should be administered at the maximum tolerable dose, it is not clearly established that the therapeutic results at dosage levels involving maximum tolerable toxicity are really superior to those with lower, better tolerated doses. 392 patients with advanced primary lung cancer were treated with 5 chemotherapy regimens including cyclophosphamide, methotrexate, vincristine, procarbazine, hydroxyurea, adriamycin and CCNU, in combinations of 3 to 7 agents. Response rates of 50% and over were registered after 8 weeks of treatment. During the same time the intensity of leukopenia, thrombocytopenia, vomiting, other digestive toxicity, neurologic disorders and alopecia was graded according to the worst observation from 0 to 4. The results show that there is no correlation between the grade of toxicity and the rate of response either for the whole group or for subgroups of patients as defined by cell type, degree of dissemination, age, or performance status. They demonstrate that the search for maximum tolerable toxicity is not a sine qua non for the best possible response to chemotherapy in primary lung cancer.
Adenocarcinoma↗
Immune depression in Trypanosoma brucei brucei infected mice. Sequential histological and immunological findings.
Pathological findings in various organs and tissues, T and B lymphocyte inability to proliferate towards several mitogens, and the appearance of serum interferon at progressive stages after intraperitoneal infection of BALB/c mice with Trypanosoma brucei brucei are reported. Heavy parasitaemia is evident throughout infection and complete hyporesponsiveness is already present on day 3. A sharp interferon production peak appears after 48 hours. The anatomopathological picture makes it clear that infection is substantially restricted to the blood. Secondary involvement of liver, lung and kidney takes the form of perivascular cuffs. These appear at relatively early stages. By contrast, spleen and lymph nodes appear to be greatly altered.
Animals↗
Tumor localization of radio-labeled antibodies against carcinoembryonic antigen in patients with carcinoma: a critical evaluation.
Purified, [131I]-labeled goat antibodies against carcinoembryonic antigen, which have been shown to localize in human carcinoma in nude mice, were injected into 27 patients with carcinoma. Patients were scanned with a scintillation camera at various intervals. In 11 patients, radioactivity was detectable in the tumor 48 hours after injection. Computerized subtraction of blood-pool radioactivity provided clearer pictures in positive cases, but in 16 patients the scans remained doubtful or negative. To study the specificity of [131I]-antibody localization, we gave some patients simultaneous injections of [125I]-labeled normal IgG. Both isotopes were measured by means of scintillation counting in tumors and normal tissues recovered after surgery. The results demonstrated that only the anti-CEA antibodies localized in tumors. However, the total antibody-derived radioactivity in the tumor was only about 0.001 of the injected dose. We conclude that, despite the present demonstration of specificity, this method of tumor detection is not yet clinically useful.
Aged↗
Use of limitations of radiolabeled anti-CEA antibodies and their fragments for photoscanning detection of human colorectal carcinomas.
Fifty-three patients with histologically proven carcinoma were injected with highly purified [131I]-labeled goat antibodies or fragments of antibodies against carcinoembryonic antigen (CEA). Each patient was tested by external photoscanning 4, 24, 36 and 48 h after injection. In 22 patients (16 of 38 injected with intact antibodies, 5 of 13 with F(ab')2 fragments and 1 of 2 with Fab' fragments), an increased concentration of 131I radioactivity corresponding to the previously known tumor location was detected by photoscanning 36-48 h after injection. Blood pool and secreted radioactivity was determined in all patients by injecting 15 min before scanning, [99mTc]-labeled normal serum albumin and free 99mTc04-. The computerized subtraction of 99mTc from 131I radioactivity enhanced the definition of tumor localization in the 22 positive patients. However, in spite of the computerized subtraction, interpretation of the scans remained doubtful for 12 patients and was entirely negative for 19 additional patients. In order to provide a more objective evaluation for the specificity of the tumor localization of antibodies, 14 patients scheduled for tumor resection were injected simultaneously with [131I]-labeled antibodies or fragments and with [125I]-labeled normal goat IgG or fragments. After surgery, the radioactivity of the two isotopes present either in tumor or adjacent normal tissues was measured in a dual channel scintillation counter. The results showed that the antibodies or their fragments were 2-4 times more concentrated in the tumor than in the normal tissues. In addition, it was shown that the injected antibodies formed immune complexes with circulating CEA and that the amount of immune complexes detectable in serum was roughly proportional to the level of circulating CEA.
Animals↗
[Occlusive syndrome due to retrocecal hernia].
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Child↗
Xenotransplantation in immunosuppressed nude mice of human solid tumors and acute leukemias directly from patients or in vitro cell lines.
Athymic nude (nu/nu) mice are widely employed for the heterotransplantation of human tumor cell lines established in vitro and tumor cells directly grafted from patients. By contrast, hemopoietic malignancies have consistently proved difficult to transplant and well-characterized human leukemias suitable for studies in nude mice are scarce. We report here our experience with subcutaneous xenotransplantation of human neoplastic cells into nu/nu mice immunosuppressed through sublethal irradiation and splenectomy (SI-nu/nu) and with an additional injection of anti-Asialo-GM1 antibodies (SIA-nu/nu) in order to eliminate natural killer activity. Thirteen out of 16 continuous cell lines established in vitro from solid tumors and 7 out of 14 human tumors obtained from fragments of surgical specimens formed a progressively growing tumor in SI-nu/nu mice. Six out of 8 in vitro established human leukemic cell lines and 5 out of 18 neoplastic hematopoietic cells directly xenotransplanted from the patient grew SIA-nu/nu mice. When the membrane and chromosome markers of neoplastic cells that grew into the mice were evaluated, only marginal differences with those of the original tumors were found. In addition, when interfering factors alter the histological aspect of the primary tumor, xenotransplantation may also be of some help in histological diagnosis. By using SI- and SIA-nu/nu mice, it is thus possible to build up several new in vivo experimental systems with fresh human tumors that may be of value in studying the efficacy of differentiation factors and immunological maneuvers on the in vivo growth of human tumors.
Animals↗