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Biomedical subjects

J F Rossi

Publications and source records attributed to J F Rossi.

At least 91 records · Page 5Linked to original sources
PubMed1990

Pilot study of neoadjuvant ifosfamide, cisplatin, and etoposide in locally advanced non-small cell lung cancer.

33 patients with locally advanced non-small cell lung cancer entered a study of neoadjuvant chemotherapy to evaluate the response rate with ifosfamide/cisplatin/etoposide and the complete resection rate and safety of surgery following chemotherapy. Chemotherapy with cisplatin 25 mg/m2, ifosfamide 1.5 g/m2, and etoposide 100 mg/m2 was given on days 1-4 of a 21 day cycle and repeated for three cycles. For responders, surgery was done 15-20 days after haematological recovery. Chemotherapy induced 5 complete responses (15%) and 18 partial responses (55%). 77% of the 33 patients had grade 3-4 neutropenia and 60% grade 3-4 thrombocytopenia. 1 patient died with a central nervous system haemorrhage. Thoracotomy was done in 21 patients but resection was only possible in 20 (61%). A complete resection was achieved in 18 patients (55%). Histology was negative for the 5 complete responses. Surgery induced no morbidity. A high response rate may be obtained with ifosfamide, cisplatin and etoposide neoadjuvant chemotherapy allowing a high complete resection rate.

Adult↗
PubMed1990

Further phenotypic evidence that nodular, lymphocyte-predominant Hodgkin's disease is a large B-cell lymphoma in evolution.

Five cases of nodular, lymphocyte predominant Hodgkin's disease (nLP HD), in which an association with (n = 3) and transformation to (n = 2) large cell lymphoma (LCL) were found, were studied with monoclonal antibodies against B-, T-, and Reed-Sternberg (R-S) cell-associated antigens and epithelial membrane antigen (EMA) on paraffin sections. Both lymphocytic (L) and histiocytic (H) cells of nLP HD and lymphoma cells of LCL expressed multiple B-cell-associated antigens (detected by LN-1/CDw75, L26, MB2, DBB.42, DBA.44, DND.53, DNA.7 antibodies) but did not react with antibodies against T-cell-associated (MT1, UCHL1/CD45RO) (one exception for CD45RO in LCL) and R-S cell-associated (Leu-M1/CD15, Ber-H2/CD30) antigens. EMA was expressed by L and H cells in all cases and conserved in LCL cells, emphasizing the frequent expression of EMA by the diagnostic cells of nLP HD. An antibody (BNH9) against blood group-related antigens (H and Y oligosaccharide antigens) that does not normally react with lymphoid cells was found to be reactive with few L and H cells in two of five and most LCL cells in four of five cases. The finding might be indicative of abnormal activation of lymphoid cells. The data reinforce current implications that nLP HD is a B-cell malignancy in evolution and that it is not truly representative of Hodgkin's disease in terms of biological and clinical behavior.

Adult↗
PubMed1990

Micro-osteoclast resorption as a characteristic feature of B-cell malignancies other than multiple myeloma.

Multiple myeloma (MM) is characterized by the presence of lytic bone lesion and frequent hypercalcaemia. These are due to an excessive osteoclastic resorption in association with a low bone formation, as demonstrated by bone histomorphometry. Conversely, B-cell malignancies other than MM are rarely associated with lytic bone lesion and/or hypercalcaemia. In this study we have analysed quantitative bone histology in 65 patients with B-cell malignancies other than MM at diagnosis: chronic lymphocytic leukaemia (CLL, n = 20), non-Hodgkin's lymphoma (NHL, n = 25), Waldenström's disease (WD, n = 14), hairy cell leukaemia (HCL, n = 6). Fifty patients presented no clinical evidence of increased bone resorption, including no lytic bone lesions radiologically detectable and/or no hypercalcaemia. 80% of these patients (40/50) had increased bone resorption parameter using quantitative bone histology, including 19/29 (65.5%) patients with CLL or WD and 21/21 (100%) patients with NHL or HCL (P less than 0.01). As a control group, seven patients lacking bone marrow involvement on bone sample presented no excessive bone resorption. However, eight patients presented lytic bone lesions and/or hypercalcaemia. All of these patients had increased resorption parameters with high numbers of osteoclasts per surface trabecular bone (mean = 35.3), as opposed to the patients lacking lytic bone lesions and/or hypercalcaemia (mean = 6.6, n = 28) and to normal individuals (mean +/- SD = 3.8 +/- 1.7 and 6.3 +/- 2.6, respectively before and after 60 years). In all the cases, excessive histologic bone resorption was mediated by mononuclear small osteoclasts (mean osteoclast length +/- SD = 27.3 +/- 4.1 as compared to normal range = 35.0 +/- 1.0, P less than 0.001). In different in vitro models, these small mononuclear osteoclasts are considered as progenitors. These data suggest an abnormal osteoclast differentiation in B-cell malignancies other than MM, probably due to differences in the production of local factors acting on bone remodelling.

Adult↗
PubMed1990

Osteoblast stimulation in multiple myeloma lacking lytic bone lesions.

The reasons why some patients with multiple myeloma (MM) do not develop severe bone loss, or even develop sclerotic bone lesions, remain unclear. In order to answer this question at the cellular and tissue level, we evaluated the histological bone condition of 10 patients with MM who never developed lytic bone lesions during the course of their disease (including two patients with sclerotic MM). Myeloma-induced bone changes in the close vicinity of myeloma cells were evaluated by quantitative histology (bone histomorphometry). All 10 patients presented a significantly increased osteoblastic activity. This was associated with an increased bone resorption in seven of the 10 cases. Three patients had a pure osteoblastic presentation. These features were the reverse of the pattern observed in seven patients with lytic bone lesions: increased bone resorption with decreased bone formation. Almost all of these 10 patients showing excessive osteoblastic activity had increased serum bone gla protein levels, a specific marker of bone formation. Finally, 90% of these patients were lambda MM (70% of them were IgG lambda MM), an immunoglobulin subtype previously associated with the sclerotic MM variants. In conclusion, a subset of patients with MM never develop severe bone loss because of the stimulation of osteoblastic activity. These patients belong to the same family as osteosclerotic MM, presenting more frequently the IgG type and lambda subtype.

Aged↗
PubMed1990

[Neurologic involvement in malignant mid-face granuloma].

We report 4 cases with neurological disorders due to lethal centrofacial granulomas of unknown origin, and we review the relevant literature. This puzzling disease is characterized by a relentless ulceration of the nose progressing toward the base of the skull, and frequently involving the cranial nerves, the meninges and later the central nervous system. The main clinical point in such situations is to ascertain that no microorganism, no cancer, no specific disease is responsible for the centrofacial lesions, since the microscopic findings may be non-specific. When the entire work-up to exclude all differential diagnoses is completed, the clinician has to deal with lethal centrofacial granuloma. This seems to be a heterogeneous disease, in most of the cases close to malignant T lymphomas. Management is based on radiotherapy, chemotherapy and renutrition with treatment of frequent infectious complications. The prognosis is poor.

Adolescent↗
PubMed1990

[Contribution of immunologic technics to the characterization of lethal midline granuloma of unknown origin].

The lethal midline granuloma is a clinical entity characterized by a relentless ulceration of the upper airway involving the nose, the palate and the face, without any demonstrable etiology. We have applied the cell membrane immunostaining techniques to twelve cases. According to the results, it seems that most of the cases are in fact T-cell lymphomas with membrane staining consistent with either precursor or mature lymphoid T-cells. Some cases, however, exhibit an immunostaining pattern compatible with other origins, the proliferating cells belonging either to the B lymphoid or to the histio-monocytic lineages. We conclude that the lethal midline granuloma is an heterogeneous group of neoplastic diseases, in the most part close to a T cell lymphoma, but with a remarkable clinical unity.

Granuloma, Lethal Midline↗
PubMed1990

Pneumocystis carinii infection of bone marrow in patients with malignant lymphoma and acquired immunodeficiency syndrome. Original report of three cases.

Pneumocystis carinii (PC) pneumonia was reported with increased frequency in patients presenting with acquired immunodeficiency syndrome (AIDS) or in patients receiving immunosuppressive chemotherapy for hemopathies. Extrapulmonary dissemination of PC is rare. In this study, three patients had PC infection of the bone marrow. Two of them presented with malignant lymphoma that had apparent immunosuppression, and the third patient presented with AIDS. In all three cases, such an infection was observed before or concomittantly with PC pneumonia. A bone marrow biopsy, bone marrow aspirate, or both can be useful, readily available tools for the diagnosis of a PC infection and especially its dissemination in patients with malignant lymphoma after intensive treatment or in patients with AIDS. The appreciation of such a dissemination may have some implications in the treatment of PC infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Osteoclast cytomorphometry and scanning electron microscopy of bone eroded surfaces during leukemic disorders.

Tartrate resistant acid phosphatase (TRAP) is a reliable histochemical marker of osteoclasts when used on tissue sections of undecalcified bone. This paper presents an original morphometric analysis which can be done after histochemical identification of osteoclasts. These bone resorbing cells were demonstrated on undecalcified bone biopsies from control subjects and patients presenting a malignant disease of the lymphocyte B lineage. Computerized analysis of the osteoclastic population revealed that: (1) all TRAP positive cells along bone trabeculae belong to a osteoclastic population; (2) that B cell malignancies had an increased bone resorption. At the scanning electron microscopic level small resorption bays (about 10 microns in diameter) were observed either associated or separated from eroded surfaces presenting abnormal appearance; TRAP staining of histological sections of undecalcified bone, coupled with morphometric studies, may help in the understanding of bone disease pathobiology.

Acid Phosphatase↗
PubMed1990

Allogeneic or autologous bone marrow transplantation for acute lymphoblastic leukemia in first complete remission.

Forty-seven patients with high risk acute lymphoblastic leukemia (ALL) received an allogeneic (allo) or autologous (auto) bone marrow transplant (BMT). Patients in both groups were comparable in terms of age, initial presentation of ALL and induction chemotherapy. Allo patients were transplanted earlier (median 3 months after CR) than auto patients (median 6.5 months after CR). Auto patients received more consolidation chemotherapy before BMT. All patients received total body irradiation 2.2 Gy/day x 5 days after cyclophosphamide 60 mg/kg x 2 (18 allo and five auto) or melphalan 140 mg/m2 (seven allo and 17 auto). Prevention of graft-versus-host disease (GVHD) was by conventional immunosuppression in 17 patients and T cell depletion in eight. Seven patients (28%) developed moderate to severe acute GVHD. Auto marrow was treated in vitro in each case. Seven patients died in CR from BMT complications (five allo and two auto). The probability of relapse was 9% for patients receiving allo BMT and 52% for patients receiving auto BMT (p less than 0.01). The disease-free survival was 71% for allo BMT and 40% for auto BMT (p = NS). Early BMT is an effective form of consolidation for high risk patients with ALL in first CR. An allogeneic anti-leukemia effect was demonstrated in this study.

Adolescent↗
PubMed1990

[Bone tissue and cancer].

Bone remodeling is a constant phenomenon balancing between osteoblastic bone formation and osteoclastic bone resorption in the neighbourhood of a cellular micro-environment including stromal and hemopoietic cells. Numerous local factors and hormones modulate such a mechanism and act synergistically, usually through the indirect production of osteoblastic coupling factors. The majority of the cytokines acting on bone remodeling possess both actions upon activation of mature osteoclasts and differentiation of hemopoietic osteoclast progenitors. Components from bone matrix which include non-collagenous bone proteins and other local factors are major products acting on bone remodeling. The presence of a cancer may determine changes in bone remodeling, directly through tumor-mediated resorption or indirectly through the action of local or systemic factors with or without tumor involvement of bone. Bone remodeling associated with cancer is usually an uncoupled phenomenon with decreased bone formation and increased bone resorption. In B-cell malignancies, abnormal bone remodeling is an early event linked to specific bone involvement. Abnormal osteoclast differentiation (micro- or macro-resorption) represents a major difference between myeloma and other B-cell malignancies. Several synergistic factors produced by tumor cells and micro-environment are usually implicated in the pathogenesis of bone lytic lesions, hypercalcemia or histomorphometric bone changes associated with cancers.

Biological Factors↗
PubMed1989

Spontaneous secretion of tumor necrosis factor-beta by human myeloma cell lines.

Abnormal bone remodelling in the vicinity of tumor cells is a common, early feature of multiple myeloma, characterized by excessive bone resorption which is mediated by local soluble factors called osteoclast activating factors (OAF). Since interleukin-1 (IL-1) and tumor necrosis factors (TNF) are potent, synergistic OAF produced by cells of the B-cell lineage, the authors investigated the spontaneous secretion of these cytokines by 11 human myeloma cell lines (HMCL). No HMCL secreted either IL-1, the most powerful OAF, or contra IL-1. In contrast, all of the lymphoblastoid cell lines assayed produced significant IL-1 activity. Ten of the 11 HMCL secreted a significant TNF activity. This was completely eliminated by an anti-TNF beta monoclonal antibody but not affected by an anti-TNF alpha antiserum. The data from this study suggest that TNF beta is involved in myeloma bone resorption, but not IL-1, which is, however, known as one of the most potent OAF.

Antibodies, Monoclonal↗
PubMed1989

[Is Stewart's malignant midline granuloma a peripheral T-cell lymphoma? Apropos of 5 cases].

Midline granuloma includes diverse clinicopathological entities, such as Wegener granulomatosis, polymorphic reticulosis, lethal midline granuloma and conventional malignant lymphoma of the nose usually of B-cell origin. The authors describe five patients with LMG clinically and pathologically typical. Using an extensive panel of monoclonal antibodies, they demonstrate an "activate" T-cell phenotype observed on the initial lesion of the face in one patient, similar to that found in two patients with LMG but studied after dissemination in peripheral T-cell lymphoma. Furthermore, many atypical cells were found in LMG, and stained with the Ki-67 monoclonal antibody, a marker of proliferating cells. These findings support the view that LMG is closely related to T-cell malignancies. Two of them were treated with recombinant Interferon alpha 2a followed by a response rapidly objective. Immunohistologic studies are very important for confirming the T-cell origin of such a disease and for selecting patients to be treated with Interferon alpha.

Adolescent↗
PubMed1988

Histologic evidence of an abnormal bone remodeling in B-cell malignancies other than multiple myeloma.

In a prospective study of the quantitative bone changes induced by B-cell cancers other than multiple myeloma (MM), but including chronic lymphocytic leukemia (CLL; n = 8), hairy cell leukemia (HCL; n = 3), and Waldenström disease (WD; n = 7), an abnormal bone remodeling close to malignant cells was found in 80% of the patients. This was observed more frequently in cases of diffuse, but not nodular, bone marrow involvement by tumor cells. More particularly, excessive bone resorption (a major feature of MM) associated with a normal to low bone formation (i.e., uncoupling bone disease) was the most frequent feature and in the same range of that observed in overt MM. However, as opposed to MM, this bone resorption was characteristically mediated by small mononucleated osteoclasts (i.e., microresorption). The same phenomena of abnormal bone remodeling, the uncoupling process, excessive bone resorption, and above all microresorption were confirmed by the detailed bone study of five cases of B-cell cancers other than MM presenting lytic bone lesions and hypercalcemia. The current findings are important for clarifying the biology of these B-cell malignant diseases, and also could be of diagnostic and prognostic value.

Adult↗
PubMed1988

Phenotypic and functional analysis of 1,25-dihydroxyvitamin D3 receptor mediated modulation of the human myeloma cell line RPMI 8226.

Several recent studies have demonstrated the presence of specific receptors for the 1,25-dihydroxyvitamin D3 (calcitriol) in activated normal lymphocytes. By DNA cellulose chromatography, we show evidence of such specific receptors in the human myeloma cell line RPMI 8226. Nanomolar concentrations of 1,25-dihydroxyvitamin D3 reduce the proliferation of RPMI 8226 cells significantly and simultaneously induce the appearance of both new properties and phenotype expression, such as butyrate esterase, enhanced expression of CD20 (B1), CD15 (Leu-M1) antigens and lambda chains, and decreased expression of the PC1 antigen using microfluorometric analysis. But such an increased expression of membrane lambda chains was not associated with an enhanced secretion of lambda chains. Furthermore, the bone resorbing activity produced normally by RPMI 8226 cells was reduced significantly after 1,25-dihydroxyvitamin D3 treatment. The possible mechanisms and significance of these new functional and phenotypic properties are discussed with respect to the B-cell lineage.

Bone Resorption↗
PubMed1988

Production of B-cell growth factor interleukin 2 and gamma interferon by peripheral blood lymphocytes from patients with chronic lymphocytic leukemia of B-cell type.

Chronic lymphocytic leukemia of B-cell type (B-CLL) is a malignant disease characterized by monoclonal proliferation of small lymphocytes of B-cell origin, usually associated with suppression of polyclonal B-cell activation (i.e., proliferation and differentiation). Normal human B-cell proliferation is controlled by different T-cell-derived lymphokines, including interleukin 2 (IL2) and gamma interferon (gamma-IFN), that account for the majority of the B-cell growth factor (BCGF) activity produced by mitogen-activated peripheral blood mononuclear cells (PBMCs). We have previously shown an increased and dysregulated secretion of IL2 in peripheral blood from patients with B-CLL. BCGF, IL2, and gamma-IFN productions by phytohemagglutinin (PHA)-stimulated PBMCs were investigated in 13 patients with active untreated B-CLL and 11 healthy donors. B-CLL PBMCs produced a significant amount of BCGF (6 U/ml) despite the low percentage of T cells (10%) associated with this disease as compared with that found in healthy donors (61%). BCGF production in normal controls and B-CLL patients was tripled after irradiation of PBMCs or addition of indomethacin. gamma-IFN secretion in B-CLL patients was decreased when compared with normal controls. Therefore, when gamma-IFN was calculated per fixed number of T cells, production was significantly higher in B-CLL patients than in normal controls, showing a dilution of the productive cells. This study suggests that T cells from B-CLL patients are functional in terms of BCGF production despite their decreased percentage and abnormalities in surface markers.

Aged↗
PubMed1988

Intensive chemotherapy with high doses of BCNU, etoposide, cytosine arabinoside, and melphalan (BEAM) followed by autologous bone marrow transplantation: toxicity and antitumor activity in 26 patients with poor-risk malignancies.

Twenty-six patients (median age 33 years) with poor-risk malignancies were treated with high-dose combination chemotherapy associating BCNU-etoposide-cytosine arabinoside and melphalan (BEAM) followed by autologous bone marrow transplantation (ABMT). Twenty-one patients had malignant lymphomas, three, acute lymphoblastic leukemia (ALL), and two, malignant thymomas. Eleven patients (group 1) were not in complete remission (CR) at the time of BEAM, and fifteen patients (group 2) were in CR. Hematological recovery occurred in all patients. The duration of aplasia and the non-hematological toxicities were similar in both groups. Ten of the eleven patients (group 1) evaluable for response achieved CR and one achieved partial remission (PR). Five patients relapsed, and five are in continuous CR with a short follow-up (median 8 months). Among the fifteen patients in CR at the time of BEAM (group 2), four patients relapsed and ten patients are in unmaintained continuous CR with a median follow-up of 15 months (one patient died in CR). The disease-free survival is 53%, with 29% for patients receiving BEAM while in relapse (group 1) and 65% for patients receiving BEAM while in CR (group 2). These data indicate that BEAM followed by ABMT can produce a high antitumor response with an acceptable toxicity in patients with poor-risk malignancies.

Adolescent↗
PubMed1988

Interleukin 2 production in bone marrow of normal individuals and patients associated with B-cell chronic lymphocytic leukaemia.

T-cells from patients with B-cell chronic lymphocytic leukaemia (B-CLL) have abnormal T4/T8 ratios and functions. Previously, we demonstrated that peripheral blood (PB) mononuclear cells from B-CLL patients secrete significant amounts of interleukin 2 (IL2) with an apparent dysregulation of accessory cells controlling this production. In this study, IL2 production was investigated in PB and in bone marrow (BM) from patients with previously untreated B-CLL, mostly in early stages of the disease, and compared to normal donors. A significant secretion was observed in both PB and BM from B-CLL patients after stimulation by phytohaemagglutinin (PHA), with lower amounts in patients with nodular involvement of BM, as compared to interstitial or diffuse involvements. To explore the role of accessory cells in controlling IL2 production, we added phorbol ester or indomethacin to the culture system or irradiated the cells before culture. Phorbol ester significantly increased the IL2 secretion in both the PB and the BM of B-CLL patients. The irradiation or the addition of indomethacin did not enhance the IL2 production in PB from B-CLL patients. However, IL2 secretion increased in the BM cells from B-CLL patients after addition of indomethacin or prior irradiation, in a similar way to that observed in PB and BM of normal controls, suggesting an apparent normal control of the IL2 production in BM from B-CLL patients. In normal controls, we demonstrated that IL2 secretion per T-cell from BM was 5.4-fold greater than that from normal PB, suggesting a very efficient role of accessory cells controlling IL2 production in normal BM.

Aged↗