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A Pileri

Publications and source records attributed to A Pileri.

At least 73 records · Page 4Linked to original sources
PubMed1996

Combined differentiating therapy for myelodysplastic syndromes: a phase II study.

An in vitro synergism between different inducers of AML cell differentiation has been previously observed. Therefore, we treated 53 myelodysplastic (MDS) patients with a low dose combination of cis-retinoic acid (cRA, 20-40 mg/day) and 1,25 alpha (OH)2 cholecalciferol [(OH)2D3, 1-1.5 micrograms/day] +/- intermittent 6-thioguanine (30 mg/m2/day). The latter was reserved for patients with bone marrow (BM) blast excess (> or = 5%). The treatment was well tolerated, without major toxicity. Among 25 patients with BM blasts less than 5%, we observed one complete, eight partial and four minor responses (response rate 52%) with a median response duration of 8 months (2 +/- 24). Median survival, which did not correlate with response, is projected at 76 months. Thirty-one patients with BM blast excess (> or = 5%), including three of the previous group who progressed to refractory anemia with excess of blasts (RAEB), were treated with the three-drug protocol. One complete, 12 partial and six minor responses were obtained (response rate 61%) with a median response duration of 6 months (2-29+). A significant difference in survival (P < 0.005) was observed between the 19 responders (median 25 months) and the 12 non-responders (median 9 months). A reduction in the transfusion need was observed in 41% of the transfusion-dependent patients with blast excess and in 53% of those without blast excess. Therefore, combined differentiating therapy seems more effective than previously reported single agent treatments and should be considered for a larger randomized study to assess its actual impact on survival of MDS patients.

Aged↗
PubMed1996

Clinical and molecular remission after allogeneic blood cell transplantation in a patient with mantle-cell lymphoma.

Mantle-cell lymphoma (MCL) is a B-cell tumour with a usually poor prognosis, characterized by the proliferation of small cleaved lymphocytes with a diffuse growth pattern. We report a polymerase chain reaction-based analysis of minimal residual disease in a patient who achieved complete remission after allogeneic blood cell transplantation (BCT). Rearrangement of the immunoglobulin heavy-chain genes was used to generate a lymphoma-specific molecular marker. Lymphoma cells were not detectable in a bone marrow sample collected 12 months after BCT. Our findings suggest that allogeneic BCT may offer a curative approach to MCL.

Adult↗
PubMed1996

Clinical and immunological studies in advanced cancer patients sequentially treated with anti CD3 monoclonal antibody (OKT3) and interleukin-2.

CD3 engagement has been used as a surrogate for antigen-specific stimulation to trigger T cell effector functions. Exogenous IL-2 has been used to prolong and amplify CD3-induced T cell activation. Previous studies have been shown that CD3 reactivity is increased in cancer patients with preactivated (> 10% HLA-DR+) T cells in the peripheral blood. In this study, we report 9 courses of a single infusion of anti-CD3 mAb (OKT3) followed by continuous infusion of intermediate dose IL-2 in 4 cancer patients [2 multiple myeloma (MM), 1 B-cell lymphoma (NHL), 1 metastatic melanoma (ME)] with advanced disease and > 10% HLA-DR+ T cells in the peripheral blood. An increase of lymphocytes, equally distributed between CD4+ and CD8+ subsets, was observed during treatment. Activation was phenotypically documented by the emergence of CD25+ cells in the peripheral blood. Unexpectedly, functional studies [including proliferation to mitogens (PHA, OKT3) and cytotoxicity assays (NK and LAK activities)] did not parallel phenotypic data and a slight decrease of all functions was observed after OKT3 and IL-2 treatment. OKT3 and IL-2 infusions were well tolerated and no limiting toxicity was observed. The treatment did not revert tumor progression in the 2 patients with progressive disease (NHL, ME) and had only minimal effects in the 2 MM patients with stable disease. These data indicate that the sequential administration of OKT3 and IL-2 had no anti-tumor activity in this small series of patients with advanced cancer who were selected for treatment because of an increased number of HLA-DR+ T cells in the peripheral blood. A discrepancy was observed between the emergence of CD25+ T cells and the clinical outcome.

Antibodies, Monoclonal↗
PubMed1995

Dysregulated Fas and Bcl-2 expression leading to enhanced apoptosis in T cells of multiple myeloma patients.

We have previously reported the presence of activated (HLA-DR+) T cells in multiple myeloma (MM) patients. These cells produce high amounts of interleukin (IL)-2 and interferon (IFN)-gamma and generate a potent antiplasma cell activity after appropriate in vitro stimulation, but they are unable in vivo to hold in check the disease. Activated T cells are highly susceptible to apoptosis, a form of programmed cell death involved in the modulation of immune responses and regulated by molecules such as Fas (CD95) and bcl-2. The aim of this study was to determine the expression of Fas and bcl-2 antigens and the susceptibility to apoptosis in T cells of MM patients. Fas+ cells were significantly higher, whereas bcl-2+ cells were significantly lower in MM patients than in the controls. MM patients with the highest number of HLA-DR+ T cells showed the highest Fas and the lowest bcl-2 expression. Two-color cytofluorometric analysis confirmed in individual cells that HLA-DR+ T cells coexpressed Fas and lacked bcl-2. Susceptibility to apoptosis was then investigated to evaluate the consequence of dysregulated Fas and bcl-2 expression. The percentage of apoptotic cells after incubation in medium alone (spontaneous apoptosis) or in the presence of methylprednisolone (MP) or anti-Fas monoclonal antibody (triggered apoptosis) was significantly higher in MM and mainly restricted to HLA-DR+ T cells. Spontaneous apoptotosis was reverted by exogenous IL-2. In conclusion, MM T cells have a dysregulated expression of Fas and bcl-2 antigens that is associated with an enhanced susceptibility to apoptosis. These data may unravel a novel mechanism by which activated MM T cells are weakened in their ability to exert an effective antitumor activity in vivo.

Antigens, Surface↗
PubMed1995

High-dose sequential chemoradiotherapy in multiple myeloma: residual tumor cells are detectable in bone marrow and peripheral blood cell harvests and after autografting.

Based on preliminary encouraging results in terms of response rate and survival, high-dose chemoradiotherapy has gained considerable interest in the treatment of patients with multiple myeloma (MM). We have evaluated the presence of residual myeloma cells in 15 of 18 patients enrolled in a high-dose sequential (HDS) chemoradiotherapy program followed by autografting. Our analysis has been performed both on bone marrow (BM) and peripheral blood (PB) cell harvests and after autografting. As it has been recently shown that B cells clonally related to malignant plasma cells are detectable in MM patients, we have developed a polymerase chain reaction (PCR)-based strategy to detect both residual B cells and plasma cells using clone-specific sequences derived from the rearrangement of Ig heavy chain (IgH) genes. The complementarity-determining regions (CDR) of IgH genes have been used to generate tumor-specific primers and probes. The constant (C) region usage defined the differentiation stage of residual myeloma cells. We report that plasma cells were detectable in PB and BM cell harvests and after transplantation in all assessable patients, irrespective of disease status. B cells were detectable in a consistent proportion of BM and PB samples at diagnosis, but only in one case at the time of PB and BM cell harvests. These cells became sometimes detectable after transplantation. Whether residual myeloma cells are clonogenic and contribute to relapse is currently unknown, and further investigations are required.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV-1 gp120.

CD4, a lymphocyte surface glycoprotein, serves as co-receptor for antigen with the T cell receptor (TCR). It is also the lymphocyte receptor for HIV by binding the gp120 viral envelope protein. Interaction of gp120 with CD4 is crucial for viral infection, but is not sufficient to allow viral entry into cells. Recombinant gp120 alters CD4+ T cell responsiveness to activation stimuli. To express its co-receptor function fully, CD4 must be laterally associated with the TCR and CD45 to form multi-receptor complexes competent to transduce potent activation signals. Here, we examine the possibility that gp120/CD4 binding alters lateral associations of CD4 with other lymphocyte surface molecules, and that assembly of abnormal multi-molecular complexes is involved in the gp120-induced CD4+ T cell dysfunction and in viral entry. In the absence of gp120, CD4 displayed high association with CD3, CD5, CD45RC, CD25, CD28, CD44, and CD53; weak association with CD2, CD38, CD45RB, CD62L, and CD26; and no association with CD45RA, CD45RO, CD11b, CD11a, CD54, CD7, CD48, CD98, CD59 CD55, HLA class I and class II molecules. Treatment with gp120 significantly increased CD4 association with CD3, CD45RA, CD45RB, CD59, CD38, CD26 and HLA class I, and decreased that with CD45RC. Specificity of these results were assessed at various levels. First, gp120 did not influence lateral associations displayed by other molecules, such as HLA class II. Second, the Leu3 mAb which binds CD4 on a site overlapping the gp120 binding site, did not elicit the same CD4 lateral associations as gp120, and finally, a direct gp120/CD4+ interaction was needed to induce the lateral associations, as shown by the observation that blocking the gp120/CD4 binding by the Leu3 mAb inhibited the gp120-induced associations. These results can be interpreted in several ways gp120/CD4 interaction could trigger an inside-out signal responsible for the associations, or gp120 could induce steric modifications of CD4 that increase its affinity for the associating molecules. Alternatively, these molecules may interact directly with gp120, bridging them with CD4. It is also possible that th e associations may be mediated by additional components, interacting with both gp120 and the associating surface molecule. The last hypothesis is likely for CD59, whose gp120-induced association with CD4 required the presence of serum in the co-capping assay. Since both CD59 and gp120 bind complement, the observed association could be mediated by complement components.

Antibodies, Monoclonal↗
PubMed1995

Plasma cell dyscrasias: classification, clinical and laboratory characteristics, and differential diagnosis.

Plasma cell dyscrasias form a heterogeneous group of diseases characterized by the expansion of the number of monoclonal bone marrow plasma cells that produce monoclonal immunoglobulins. Sensitive electrophoretic methods have shown that the incidence of these diseases is as high as 5% in adult individuals. Thus, the majority of cases should be considered to be a normal phenomenon. A few transform into neoplastic diseases, plasma cells becoming responsible for lytic bone lesions, the hallmark of MM. The distinction of benign and malignant forms is frequently difficult at presentation. We can easily recognize solitary myeloma, overt myeloma and plasma cell leukaemia, which require immediate chemotherapy. Therapy could be safely withheld in all the remaining forms, which require only follow-up. Thus, we suggest that plasma cell dyscrasias should be classified simply into two main groups according to the need of immediate chemotherapy. The appearance of new bone lesions and the increase of the M-component level remain the only two criteria that define malignant transformation. Several clinical and laboratory prognostic parameters indicate the risk of transformation, and hence how close the follow-up of the patient should be. Parameters related to the expansion of the plasma cell clone (percentage of bone marrow plasma cells, M-component level, lytic bone lesions and beta 2-microglobulin) are not always very low and very high in the benign and malignant forms, respectively, and frequently overlap in patients with intermediate plasma cell expansions. On the contrary, all parameters related to the intrinsic malignancy of the plasma cells (plasma cell LI, Karyotypic abnormalities and molecular alterations) have, by definition, to be normal in the benign forms. MRI is a new tool that may, early on, reveal lytic bone lesions undetectable by conventional radiography.

Clinical Laboratory Techniques↗
PubMed1995

Haematological support of high-dose sequential chemotherapy: clinical evidence for reduction of toxicity and high response rates in poor risk lymphomas.

The toxicity and feasibility of a high-dose sequential (HDS) chemotherapy programme delivered with growth factor support were evaluated in patients with intermediate and high-grade non-Hodgkin's lymphoma (NHL) or with progressive Hodgkin's disease. The scheme includes the sequential administration of single cytotoxic drugs at very high doses followed by intensified treatment with circulating progenitor autograft. In some instances, the original HDS scheme, initially designed at the Milan Cancer Center, was partially modified and intensified with a preliminary debulking phase. The use of G-CSF (filgrastim) made toxicity in the high-dose phase acceptable and allowed good harvests of peripheral blood progenitor cells (PBPC); the use of PBPC in the final autografting phase resulted in low haematological toxicity. Of 71 patients with NHL treated at our institution with either the original or the intensified HDS version, the overall toxicity-related mortality was 5.6%, thus comparable to lethal toxicity commonly associated with conventional chemotherapy. Adequate PBPC harvests are crucial for good tolerability of the programme. Optimal harvests are generally obtained in patients without neoplastic marrow infiltration while patients with marrow disease often have a poorer mobilisation. However, an optimally time-spaced chemotherapy debulking might also restore sufficient mobilisation in these latter patients. In terms of therapeutic efficacy, HDS had produced promising results since the initial experience in relapsed patients. More recently, HDS was evaluated as first-line treatment in a series of 22 consecutive patients, presenting with advanced-stage, intermediate-grade NHL other than diffuse large cell subtype. A CR rate of 82% was obtained following HDS, with a projected survival of 86% at five years. Thus, delivery of an intensive high-dose chemotherapy programme with haematopoietic growth factor support was found to be feasible and reasonably safe. The high anti-tumour efficacy of such a scheme makes it suitable for wider applicability in all those chemosensitive tumours where a dose increase might enhance the chance of cure.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Both early and committed haemopoietic progenitors are more frequent in peripheral blood than in bone marrow during mobilization induced by high-dose chemotherapy + G-CSF.

Haemopoietic growth factor administration following high-dose chemotherapy markedly amplifies progenitor cell pool in the peripheral blood (PB). Collection and reinfusion of these cells enable rapid haemopoietic reconstitution following autograft. Less is known on engraftment potentiality of bone marrow (BM) cells taken under analogous conditions. To investigate this tissue, PB and BM were evaluated simultaneously during maximal mobilization in a series of 14 patients undergoing the HDS chemotherapy programme. A significantly higher growth of committed progenitors was found from PB rather than from BM (663 +/- 123 v 267 +/- 40 CFU-GM/10(5) MNC, respectively). Also, significantly more CFU-GM could be collected by a median of three leukaphereses, compared to those harvested from BM (158 +/- 31 v 16 +/- 4 x 10(4) CFU-GM/kg, respectively). Most mobilized CFU-GM were phenotypically immature (CD15-); in addition, circulating cells included primitive progenitors, as assessed by LTC-IC assay, or by evaluation of non-proliferating pre-CFU-GM, selected by an anti-CD71 immunotoxin. The amount of pre-CFU-GM determined by both techniques was consistently higher in PB than in BM. Moreover, a direct correlation could be established between circulating CFU-GM and primitive precursors. Thus, during optimally induced mobilization, PB contains many more haemopoietic progenitors, of both committed and primitive stages, than does BM. Under such conditions, PB is probably the best source of material for graft purposes.

Adult↗
PubMed1995

CD3-induced T-cell activation in the bone marrow of myeloma patients: major role of CD4+ cells.

A large expansion of activated T cells (CD3+CD25+) with the potential to act as anti-tumour effector cells is inducible in multiple myeloma (MM) patients by culturing bone marrow mononuclear cells (BMMCs) with the anti-CD3 monoclonal antibody (mAb) OKT3. The aim of this study was to provide a greater characterization of CD3-activated T cells. On day 6, most T cells coexpressed the CD11a, CD18, CD54, CD45R0 antigens and consisted of activated (CD25+) CD4+ and CD8+ cells in nearly equal proportions. Kinetics studies showed that CD4+CD25+ cells proliferated more rapidly and peaked earlier than CD8+CD25+ cells. When experiments were performed with purified subpopulations by removing CD4+ cells (resulting in CD8+ BMMCs) or by removing CD8+ cells (resulting in CD4+ BMMCs). T-cell activation and autologous plasma cell decrease were observed in CD4+ BMMCs only. Transwell cultures showed that CD4 help was necessary to make CD8+ BMMCs susceptible to CD3 stimulation. Relevant amounts of IL-2 were found in the supernatants of CD4+ BMMCs cultures, whereas no secretion of IL-4 was detected, indicating a Th1-like profile of CD3-activated CD4+ cells. These data indicate that CD4+ cells proliferate earlier and provide optimal help to induce the subsequent expansion of CD8+ cells after CD3 stimulation of MM BMMCs. Adequate stimulation of CD4+ cells is therefore essential in any strategy aiming to recover T-cell-mediated immunity in MM.

Bone Marrow↗
PubMed1995

Retinoic acid inhibits the growth of human myeloma cells in vitro.

Retinoic acid has been shown to induce growth inhibition in a variety of cell types including human myeloma cell lines. Bone marrow plasma cells from 31 multiple myeloma (MM) patients were cultured to investigate the activity of 13-cis-retinoic acid (cRA), all-trans-retinoic acid (tRA), interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and dexamethasone (DEX), alone or in combination, on in vitro proliferation and immunoglobulin (Ig) secretion. Both cRA and tRA inhibited proliferation: the labelling index (LI) of treated cultures/controls, was 0.47 +/- 0.05 (mean +/- standard error mean, M +/- SEM) P < 0.0001, and 0.67 +/- 0.04 (M +/- SEM), P < 0.0001, respectively. The inhibitory effect of cRA was significantly superior to tRA (P = 0.0129) and IFN-alpha, similar to IFN-gamma and DEX. The combinations of cRA + IFN alpha, tRA + IFN-gamma, tRA + DEX did not show any synergistic effect on myeloma proliferation. In contrast, the combination cRA + DEX (0.29 +/- 0.04, M +/- SEM) markedly increased the effect of both cRA and DEX used as single agents. Ig synthesis was not significantly affected by CRA, tRA, IFN-gamma and the combination tRA + IFN-gamma. As expected, only IFN-alpha (P = 0.002) and DEX (P < 0.001) inhibited Ig production. The combinations cRA + IFN-alpha, cRA + DEX and tRA + DEX decreased Ig secretion to the same extent as IFN-alpha and DEX alone respectively. In conclusion, our data indicate that tRA and especially cRA strongly inhibited plasma cell proliferation but had no effect on Ig synthesis. The combination of cRA + DEX showed the highest degree of inhibitory activity of all cytokines, alone or in combination.

Antibodies, Neoplasm↗
PubMed1995

T cells in multiple myeloma: is this a reliable population to count on as antitumor effector cells?

Multiple Myeloma (MM) is still a long way from being cured. Disease evolution has been associated with a number of phenotypic and functional alterations in T cells, indicating that a progressive deterioration of cellular immunity might facilitate the negative outcome. Despite these correlations, specific interactions between tumor and T cells have been demonstrated indicating that a population liable to be exploited as antitumor effector cells exists in vivo. This review aims at recording some evidence obtained in our laboratory demonstrating that MM T cells, despite the variety of their alterations, can still generate potent antitumor activity. Adequate stimulation, however, is required to exploit this ability.

Animals↗
PubMed1995

Interferon-gamma in multiple myeloma.

Biological heterogeneity is a characteristic of multiple myeloma. A dysregulated cytokine network underlies the various phases of the disease. Numerous cytokines, either promoting or inhibiting plasma cell growth, are involved in tumor control. Interferon-gamma (IFN-gamma) showed the most powerful inhibiting activity on myeloma cell proliferation. This effect was demonstrated on IL-6 dependent myeloma cell lines, but not on IL-6 independent ones. It was also evident on fresh explanted bone marrow myeloma cells. The antiproliferative effect of IFN-gamma seems mainly due to the inhibition of IL-6, the central myeloma growth factor. IL-6 inhibition may occur at various levels: a downregulation of IL-6 receptor has been reported, and also a block of the IL-6 signal transduction pathway via interaction with cytoplasmic proteins such as p91 has been suggested. Our findings showed that IFN-gamma strongly inhibited myeloma cell proliferation to the same extent as dexamethasone (DEX), whereas interferon-alpha (IFN-alpha) inhibited Ig secretion. The combined use of interferons (IFNs) showed inhibitory activities both on proliferation and Ig synthesis that paralleled the effects of DEX. In some cases, IFN-gamma was also shown to augment monoclonal immunoglobulin secretion suggesting a possible differentiating activity on plasma cells. The in vitro data encouraged pilot studies to evaluate the in vivo antitumor effects of IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1995

Circulating progenitors following high-dose sequential (HDS) chemotherapy with G-CSF: short intervals between drug courses severely impair progenitor mobilization.

Sequential administration of high-dose chemotherapy courses possibly allows extensive in vivo purging before circulating progenitor collection for autograft. To evaluate whether progenitor cell mobilization was negatively affected by repeated high-dose chemotherapy courses, we studied 23 lymphoma patients undergoing the HDS regimen. The scheme includes the sequential administration of cyclophosphamide (CY) given at 7 g/m2 and etoposide (VP16) given at 2 g/m2, each followed by G-CSF (filgrastim) at 5 micrograms/kg/day. Eleven patients received the standard HDS sequence, with a short interval between first and second myelotoxic courses of less than 45 days (median: 30 days); the remaining 12 patients received a modified HDS where the interval between first and second high-dose course was protracted over 2 months (median: 70 days); in this latter group, 2 to 4 conventional debulking courses were delivered prior to HDS. In patients receiving the standard HDS, progenitor mobilization following the first course was consistently high (median circulating CFU-GM/ml peak value: 29,022); however, significantly lower values were observed at the second course (median CFU-GM/ml peak value 3757, P = 0.002). Circulating BFU-E and CD34+ cell values paralleled those of CFU-GM. No significant difference was observed in progenitor mobilization following either course in patients receiving HDS with extended interval (median circulating CFU-GM/ml peak value: 14,363 vs 9208, at first and second course respectively, P = 0.27). Eleven patients had their progenitor cells harvested following the second delayed course and 2-4 leucaphereses allowed very satisfactory harvests in all of them (CFU-GM/kg ranging from 39-340 x 10(4)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Interaction between endothelium and CD4+CD45RA+ lymphocytes. Role of the human CD38 molecule.

CD38 is a type II transmembrane glycoprotein, which is widely used as a marker for immature and activated lymphocytes, as well as plasma cells. Although its functional role and natural ligand are not known, CD38 has been shown to transduce activation signals to lymphocytes. Our work shows that CD38 is preferentially expressed by CD4+CD45RA+ cells, but not by CD4+CD45R0+ cells. CD4+CD45RA+ cells are reported to respond poorly to stimuli acting through the CD3/TCR in vitro and to display unique migration pathways in vivo. Cross-linking of CD38 by mAb did not overcome the hyporesponsiveness of CD4+ resting/naive cells to several activation stimuli; in contrast, CD38 engagement by mAb specifically inhibited their binding with human vein endothelial cells. These data suggest that CD38 may play a role in lymphocyte migration. The same inhibitory effect was detected on the (human x mouse) hybrid cell line CP410.A10, which expresses human CD38, but not on its CD38- subclone CP14. CD38 mAb did not inhibit the conventional binding assay between endothelium and several human CD38+ T and B cell lines. However, the inhibition was apparent when the binding assay was performed at 4 degrees C on a rocking shelf, conditions that minimized integrin function. These data suggest that CD38 mediates weak cell binding to endothelium, which is effective even in dynamic conditions. These features are reminiscent of those exerted by selectins, which are adhesion molecules that account for leukocyte rolling on vascular endothelial cells and play an important role in lymphocyte homing.

ADP-ribosyl Cyclase↗
PubMed1994

Recombinant interferon-gamma inhibits the in vitro proliferation of human myeloma cells.

Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and dexamethasone (DEX) have shown anti-tumour effects in multiple myeloma (MM) cells. Bone marrow plasma cells from 39 MM patients were cultured to clarify the intensity and specific activity of each compound on bromo-deoxyuridine (BrdUrd) uptake and immunoglobulin (Ig) secretion. BrdUrd uptake was inhibited by recombinant human IFN-gamma (100 U/ml) and by DEX (10(-6) M). The stimulation index (StI), i.e. labelling index (LI) of treated samples/controls, was 0.49 +/- 0.09 (mean +/- standard error of the mean, M +/- SEM), P = 0.0003, and 0.52 +/- 0.07 (M +/- SEM), P < 0.0001, respectively. Ig secretion was reduced by IFN-alpha (100 U/ml) and DEX. The secretion index (SI), i.e. Ig quantitation of treated samples/controls, was 0.04 (M +/- SEM), P < 0.0001, and 0.52 +/- 0.04 (M +/- SEM), P < 0.0001, respectively. Finally, IFN-gamma inhibits BrdUrd uptake only and IFN-alpha secretion only. In 18 patients the simultaneous addition of IFN-alpha plus IFN-gamma mainly parallel the effect of IFN-gamma on BrdUrd uptake and IFN-alpha on secretion, but not result in any additive or synergistic effect, though both BrdUrd uptake and Ig secretion were decreased to about the same extent as with DEX. These data indicate that the combination of IFN-alpha plus IFN-gamma and DEX are the strongest inhibitors of both BrdUrd uptake and secretion. Since IFN-alpha and IFN-gamma appear to have a different mechanism of action, their combined use could be considered as a possible new treatment strategy.

Bone Marrow↗
PubMed1994

Correlation between disease activity and T-cell CD3 zeta chain expression in a B-cell lymphoma.

The T-cell receptor (TCR)/CD3 complex is the surface molecule responsible for the highly specific response to foreign antigens, including tumour-associated antigens. and correlations have been observed with disease status. Recently, low amounts of CD3 gamma and CD3 zeta chains in the CD3/TCR complex have been reported in long-term tumour-bearing mice as a possible mechanism for the impaired T-cell responses. In this study we report a B-cell lymphoma in which T-cell CD3 zeta expression correlated with disease activity.

CD3 Complex↗