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Biomedical subjects

M Federico

Publications and source records attributed to M Federico.

At least 55 records · Page 3Linked to original sources
PubMed1999

Identification of families with hereditary breast and ovarian cancer for clinical and mammographic surveillance: the Modena Study Group proposal.

Hereditary factors play a fundamental role in the pathogenesis of breast cancer (BC). Approximately 15-20% of all BCs have been reported to show familial clustering. In spite of the recent demonstration and chromosomal localization of BC predisposing genes, clinical clues and careful inspection of pedigree still remain major instruments in HBC diagnosis. The aim of the present study was to develop minimum operational criteria for the selection of family groups at high risk of developing BC. Following a stepwise procedure, families were stratified into four clusters with increasing probability of genetic involvement. So far, 317 BC-prone families have been identified and distributed in the four groups, and 151 high risk women underwent our clinical and mammographic surveillance program. Among these, after a mean follow-up of 24 months, six BCs and one OC were diagnosed (one BC and one OC occurred in the same woman) and one 'interval' BC was observed. Since the prevalence rate so far detected is dramatically higher than that seen at the first round of Italian population-screening programs, our preliminary data support the usefulness of the proposed procedure in selecting high risk individuals.

Adult↗
PubMed1999

Clinical characteristics, treatment outcome and survival of 36 adult patients with primary anaplastic large cell lymphoma. Gruppo Italiano per lo Studio dei Linfomi (GISL).

BACKGROUND AND OBJECTIVE: Although in recent years anaplastic large-cell lymphoma (ALCL) has emerged as a distinct clinico-pathological entity, a gold standard for treatment has still not been defined. Goals of our histologic, phenotypic and clinical study were to present clinical findings, treatment outcome and survival rates of a small, but highly homogeneously treated, series of patients. DESIGN AND METHODS: From April 1991, 36 newly diagnosed adult patients with systemic ALCL CD30+, entered a prospective non-randomized trial in one of the institutions participating in a GISL (Gruppo Italiano per lo studio dei Linfomi) study and were treated with a MOPP/EBV/CAD hybrid scheme. Chemotherapy (CHT) was administered every 28 days, for a total of 6 cycles. After CHT, 19 patients received radiation therapy (RT) to the site of previously involved fields. Kaplan and Meier and log-rank tests were used for statistical analysis. RESULTS: The overall complete remission rate was 78%, the partial remission rate was 6%. The overall survival rate at 74 months was 69%. No statistically significant differences in response or survival rates were noted comparing ALCL-HL and -CT subgroups, T+ Null- and B- subtypes, or ALCL-HL and -CT, with different phenotypes. In the analysis of patients with T+ Null phenotype treated with CHT+RT in comparison with B-ALCL patients who had the same treatment, we observed statistically significant differences in the survival rate (p=0.048). No prognostic factors predictive of response or survival were identified. INTERPRETATION AND CONCLUSIONS: Our results show that using MOPP/ABV/CAD the results, in terms of remission rate and survival, are similar to those obtained with 3rd generation CHT regimens. The diagnosis of T and Null ALCL is the most important prognostic factor, because it is associated with a very good survival, even in patients with a high prognostic index. Finally, we believe that longer follow-ups are needed to evaluate long-term survival and toxicity with different treatments.

Adolescent↗
PubMed1998

Long-term results from MOPPEBVCAD chemotherapy with optional limited radiotherapy in advanced Hodgkin's disease.

The purpose was to verify the 5-year results of the MOPPEBVCAD chemotherapy regimen with limited radiotherapy in relation to the promising preliminary data. Mechlorethamine, vincristine, procarbazine, prednisone, epidoxorubicin, bleomycin, vinblastine, lomustine, melphalan, and vindesine were delivered according to a schedule derived through hybridization, intensification, and shortening of the corresponding alternating CAD/MOPP/ABV regimen. Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. This multicenter, controlled, nonrandomized trial involved 145 eligible patients. Radiotherapy was administered to 47 patients, 46 of whom were in complete remission after chemotherapy. Remissions were complete in 137 patients (94%), partial in 4 (3%), and null in the remaining 4. Tumor-specific, overall, relapse-free, and failure-free survival at 5 years were 0.89, 0.86, 0.82, and 0.78, respectively. Hematologic toxicity was considerable, whereas nonhematologic side effects were fully acceptable. Most of the unfavorable prognostic factors lost their clinical weight. Only age and lymphocyte depletion histologic type were statistically correlated with major follow-up endpoints; performance status and bone marrow involvement were subordinate to age. Seven patients developed a second cancer (including 3 myelodysplasias). MOPPEBVCAD with selected radiotherapy is a highly effective regimen in advanced Hodgkin's disease. Early and late toxicity are no more severe than what would be expected with other alternating or hybrid regimens. A comparison with ABVD, which is currently considered the standard regimen for advanced Hodgkin's disease, is needed.

Adolescent↗
PubMed1998

Productive human immunodeficiency virus-1 infection of purified megakaryocytic progenitors/precursors and maturing megakaryocytes.

We have evaluated the susceptibility to human immunodeficiency virus (HIV)-1 infection of in vitro grown megakaryopoietic progenitors/precursors and maturing megakaryocytes (MKs), based on the following approach: (1) human hematopoietic progenitor cells (HPCs), stringently purified from peripheral blood and grown in serum-free liquid suspension culture supplemented with thrombopoietin (Tpo), generated a relatively large number of >/= 98% to 99% pure megakaryocytic precursors and then mature-terminal MKs; (2) at different days of culture (ie, 0, 5, 8, 10) the cells were inoculated with 0.1 to 1.0 multiplicity of infection (m.o.i.) of the lymphotropic NL4-3 or 0.1 m.o.i. of the monocytotropic BaL-1 HIV-1 strain; (3) finally, the presence of viral mRNA and proteins was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR)/in situ hybridization and antigen capture assays, respectively, on day 2 to 12 of culture. MKs derived from day 0 and day 5 BaL-1-challenged cells do not support viral replication as assessed by p24 enzyme-linked immunosorbent assay (ELISA) and RT-PCR. On the contrary, HIV transcripts and proteins were clearly detected in all NL4-3 infection experiments by RT-PCR and p24 assay, respectively, with the highest viral expression in day 5 to 8 challenged MKs. In situ hibridization studies indicate that the percentage of HIV+ MKs varies from at least 1% and 5% for day 0 and day 5 infected cells, respectively. Production of an infectious viral progeny, evaluated by the capability of culture supernatants from day 5 NL4-3-challenged MKs to infect C8166 T-lymphoblastoid cell line, was consistently observed (viral titer, approximately 5 x 10(3) tissue culture infectious dose50/mL/10(6) cells). Exposure of MKs to saturating concentration of anti-CD4 OKT4A monoclonal antibody (MoAb), which recognizes the CD4 region binding with the gp120 envelope glycoprotein, markedly inhibited HIV infection, as indicated by a reduction of p24 content in the supernatants: because the inhibitory effect was incomplete, it is apparent that the infection is only partially CD4-dependent, suggesting that an alternative mechanism of viral entry may exist. Morphologic analysis of day 12 MKs derived from HPCs infected at day 0 showed an impaired megakaryocytic differentiation/maturation: the percentage of mature MKs was markedly reduced, in that approximately 80% of cells showed only one nuclear lobe and a pale cytoplasm with few granules. Conversely, megakaryocytic precursors challenged at day 5 to 8 generated fully mature day 10 to 12 MKs showing multiple nuclear segmentation. Thus, the inhibitory effect of HIV on the megakaryopoietic gene program relates to the differentiation stage of cells subjected to the viral challenge. Finally, HPCs treated with 20 or 200 ng/mL of recombinant Tat protein, analyzed at different days of culture, showed an impaired megakaryocytopoiesis comparable to that observed in HIV-infected cells, thus suggesting that Tat is a major mediator in the above described phenomena. These results shed light on the pathogenesis of HIV-related thrombocytopenia; furthermore, they provide a model to investigate the effects of HIV on megakaryocytic differentiation and function.

Adult↗
PubMed1998

gag, vif, and nef genes contribute to the homologous viral interference induced by a nonproducer human immunodeficiency virus type 1 (HIV-1) variant: identification of novel HIV-1-inhibiting viral protein mutants.

We previously demonstrated that expression of the nonproducer F12-human immunodeficiency virus type 1 (HIV-1) variant induces a block in the replication of superinfecting HIV that does not depend on the down-regulation of CD4 HIV receptors. In order to individuate the gene(s) involved in F12-HIV-induced interference, vectors expressing each of the nine F12-HIV proteins were transfected in HIV-susceptible HeLa CD4 cells. Pools of cell clones stably producing each viral protein were infected with HIV-1, and virus release was measured in terms of reverse transcriptase activity in supernatants. We hereby demonstrate that HeLa CD4 cells expressing the F12-HIV gag, vif, or nef gene were resistant, to different degrees, to infection with T-cell-line-adapted HIV-1 strains. Conversely, expression of either the tat, rev, or vpu F12-HIV gene increased the rate of HIV release, and no apparent effects on HIV replication were observed in cells expressing either the F12-HIV vpr, pol, or env gene. No variation of CD4 exposure was detected in any of the uninfected HeLa CD4 pools. These data indicate that F12-HIV homologous viral interference is the consequence of the synergistic anti-HIV effects of Gag, Vif, and Nef proteins. Retrovirus vectors expressing F12-HIV vif or nef allowed us to further establish that the expression of each mutated protein (i) inhibits the replication of clinical HIV-1 isolates as well, (ii) impairs the infectivity of the virus released by cells chronically infected with HIV-1, and (iii) limitedly to F12-HIV Vif protein, induces HIV resistance in both vif-permissive and vif-nonpermissive cells. The levels of action of F12-HIV vif and nef anti-HIV effects were also determined. We observed that HIV virions emerging from the first viral cycle on F12-HIV vif-expressing cells, although released in unaltered amounts, had a strongly reduced ability to initiate the retrotranscription process when they reinfected parental HeLa CD4 cells. Differently, we observed that expression of F12-HIV Nef protein affects the HIV life cycle at the level of viral assembling and/or release. For the first time, an inhibitory effect on the HIV life cycle in both acutely and chronically infected cells induced by mutated Vif and Nef HIV-1 proteins is described. These genes could thus be proposed as new useful reagents for anti-HIV gene therapy.

Amino Acid Sequence↗
PubMed1998

[High prevalence of hepatitis C virus infection in patients with non-Hodgkin's lymphoma at the onset. Preliminary results of an Italian multicenter study].

143 patients with non-Hodgkin lymphoma (NHL) at the onset entered this perspective study on NHL-associated risk factors. They were 87 males and 56 females with a mean age of 52.3 years (range 14.6-82.3). An associated hepatitis C virus (HCV) infection was found in 16 of the 143 NHL cases (11.2%; 95% CI 6.5-17.5). They were 11 males and 5 females [mean age 59.9] year with disseminated (13/16) or localized NHL disease (3/16)]. The NHL histological subgroup was low grade (6/16), intermediate grade (2/16) or high grade (8/16). The cell origin was B in 15/16 cases and B cell-T cell rich in 1/16. The discovery of HCV infection was contemporary to lymphoma diagnosis in 6/16 cases but preceded the NHL onset in the other 10 patients. In these 10 patients the median time between HCV infection diagnosis and NHL onset was 3.6 years (range 1-14.5). These data confirm that in Italy the prevalence of HCV infection in patients with NHL (11.2%) is significantly higher than expected in the general population (1.3-3.2%). The finding that, in most cases, HCV infection was definitely antecedent to NHL onset, usually by years, adds evidence to the possible causative role of the HCV in lymphomagenesis.

Adolescent↗
PubMed1998

Weekly administration of vincristine, cyclophosphamide, mitoxantrone and bleomycin (VEMB) in the treatment of elderly aggressive non Hodgkin's lymphoma. Gruppo Italiano per lo Studio dei Linfomi.

BACKGROUND AND OBJECTIVE: Aim of the study was to assess the efficacy of VEMB, a short-lasting therapeutic regimen (50 days) which alternates two myelotoxic drugs (cyclophosphamide and mitoxantrone) every week with two less hematologically toxic drugs (vincristine and bleomycin) in the treatment of aggressive NHL in the elderly (over 70). DESIGN AND METHODS: Between November 1994 and March 1996, 37 patients aged more than 70 years, with highly or moderately malignant NHL (according to the Working Formulation) have been enrolled into the study. The stage of the disease ranged between II and IV according to Ann Arbor. Mean age was 77 years; 14 patients (38%) had stage IV; 19 patients (51%) had LDH higher than normal; 26 patients (70%) had extranodal and 9 patients (24%) had bulky disease at time of diagnosis. RESULTS: Sixty-two percent of patients achieved a complete and 22% a partial remission. Non-responders amounted to 5%. Four patients (11%) died during the therapy. Nine patients (24%) experienced grade III-IV neutropenia. The most frequently observed event was mild neurotoxicity (43% of cases). The overall survival rate at 30 months was 55%. DFS at 24 months was 66%. INTERPRETATION AND CONCLUSIONS: VEMB is a therapeutic regimen whose efficacy is comparable to that of the other derived MACOP-B therapeutic regimens used in the elderly NHL. It has proved to have a good feasibility, though the number of toxic deaths should not be neglected.

Aged↗
PubMed1998

Efficacy of two different ProMACE-CytaBOM derived regimens in advanced aggressive non-Hodgkin's lymphoma. Final report of a multicenter trial conducted by GISL.

BACKGROUND AND OBJECTIVE: To compare the efficacy of ProME(Epidoxorubicin)CE-CytaBOM (PE-C) and ProMI(Idarubicin)CE-CytaBOM (PI-C) in the treatment of adult patients with aggressive non Hodgkin's lymphoma in a multicenter randomized controlled trial performed by 18 centers of the Italian Lymphoma Study Group (GISL). DESIGN AND METHODS: One hundred and twenty-eight and 122 patients were randomly assigned to receive either 6 courses of PE-C or PI-C, respectively. Some patients achieving complete remission with induction therapy participated in another randomized study comparing no further therapy versus maintenance therapy consisting of four blocks of two drugs. RESULTS: The rate of CRs was 62% and 64% for patients treated with PE-C and PI-C, respectively (p = 0.51). The 5-year relapse-free survival was 60% for PE-C and 53% for PI-C (p = 0.29). The estimated relapse-free disease survival rates at 4 years were 75% for patients in the consolidation group and 57% for those in the observation group (p = 0.11). Patients alive in first complete remission 4 years after study entry were estimated to be 39% in the PE-C arm and 38% in the PI-C arm (p = 0.90). The 3-year and 5-year estimated survival rates were 61% and 55% for the PE-C group and 56% and 47% for the PI-C group (p = 0.26). Fatal toxicities occurred in 7 patients (2.9%) with active disease and in 4 patients (1.7%) in complete remission. Stage (p = 0.04), bulky disease (p = 0.02), serum LDH (p = 0.0006), serum albumin (p = 0.0051), hemoglobin (p = 0.0011), performance status (p = 0.0001), International prognostic index (p < 0.0001) and the index proposed by the French group G.E.L.A. (p < 0.0001) were of prognostic value. In a multivariate analysis (Cox regression model) alternatively IPI alone or G.E.L.A. index plus performance status emerged as independent prognostic factors. INTERPRETATION AND CONCLUSIONS: The present study indicates that epirubicin and idarubicin in a combined chemotherapy regimen, have similar activities. The toxic profile also indicates the safety of both anthracyclines at the dosages employed, suggesting their possible dose escalation in a combined chemotherapy setting. PE-C and PI-C were both effective and feasible regimens in an outpatient setting, with acceptable cardiovascular toxicity. The trend toward a better outcome in patients undergoing consolidation therapy after the achievement of a complete remission, warrants further investigation.

Adolescent↗
PubMed1997

Human immunodeficiency virus (HIV)-resistant CD4+ UT-7 megakaryocytic human cell line becomes highly HIV-1 and HIV-2 susceptible upon CXCR4 transfection: induction of cell differentiation by HIV-1 infection.

Recent findings have shown that the expression of the seven trans-membrane G-protein-coupled CXCR4 (the receptor for the stromal cell-derived factor [SDF]-1 chemokine) is necessary for the entry of T-lymphotropic human immunodeficiency virus (HIV) strains, acting as a coreceptor of the CD4 molecule. In the human system, the role of CXCR4 in HIV infection has been determined through env-mediated cell fusion assays and confirmed by blocking viral entry in CD4+/CXCR4+ cells by SDF-1 pretreatment. We observed that the human megakaryoblastic CD4+ UT-7 cell line fails to express CXCR4 RNA and is fully resistant to HIV entry. Transfection of an expression vector containing the CXCR4 c-DNA rendered UT-7 cells readily infectable by different T-lymphotropic syncytium-inducing HIV-1 and HIV-2 isolates. Interestingly, HIV-1 infection of CXCR4 expressing UT-7 cells (named UT-7/fus) induces the formation of polynucleated cells through a process highly reminiscent of megakaryocytic differentiation and maturation. On the contrary, no morphologic changes were observed in HIV-2-infected UT-7/fus cells. These findings further strengthen the role of CXCR4 as a molecule necessary for the replication of T-lymphotropic HIV-1 and HIV-2 isolates and provide a useful model to study the functional role of CD4 coreceptors in HIV infection.

CD4 Antigens↗
PubMed1997

A pilot study on the use of the ProMACE-CytaBOM regimen as a first-line treatment of advanced follicular non-Hodgkin's lymphoma. Gruppo Italiano per lo Studio dei Linfomi.

BACKGROUND: The role of intensive conventional dose chemotherapy in advanced low grade non-Hodgkin's lymphomas is a matter of debate. The Gruppo Italiano per lo Studio dei Linfomi conducted a study to evaluate the efficacy and toxicity of a third-generation polychemotherapeutic regimen, ProMACE-CytaBOM, as a first-line therapy in a selected group of patients with advanced follicular non-Hodgkin's lymphoma (Fo-NHL) who were younger than 60 years. METHODS: Thirty-nine patients were included in the study (14 males, 25 females; median age, 44 years; age range, 22-60 years). Their WF histotypes were B (9 patients), C (23 patients), and D (7 patients). All of the patients had disease in an advanced clinical stage (Stage III, 15 patients; Stage IV, 24 patients), and 9 patients had B symptoms. According to the age-adjusted International Prognostic Index (IPI), 20 patients exhibited low-intermediate risk, 14 high-intermediate risk, and 5 high risk. Three of the patients were not considered evaluable because they withdrew their consent after three (one patient) and four (two patients) cycles of therapy (one of these patients was in complete remission [CR], and two were in partial remission [PR]). Of the 36 evaluable patients, 4 received IF-RT after the 6 planned cycles of therapy. RESULTS: CR was achieved in 20 patients (55.5%) and PR in 14 (38.8%). One patient (2.7%) experienced disease progression during the treatment program. Eight of the 20 patients with CR (40%) relapsed. Eight patients (22.2%) died: 6 died of disease progression, 1 died of therapy consequences, and 1 died of an unrelated cause. With a median follow-up of 49 months (range, 28-79 months), the disease free survival rate was 60%. The overall survival rate was 80% after a median follow-up of 44 months (range, 3-79 months). The IPI stratification of patients showed a borderline statistical difference in terms of time to treatment failure and overall survival. The main hematologic toxicity was neutropenia (Grade 3 in approximately 10% of patients). One patient died of sepsis. Cotrimoxazole prophylaxis was always given. Cardiac toxicity (Grade 3) was observed in 1 patient at the end of the planned therapy. The average relative dose intensity of the drugs was 89% of the projected dose, without the regular use of growth factors. CONCLUSIONS: This study indicates that ProMACE-CytaBOM could be a suitable regimen for adult patients with advanced Fo-NHL, allowing a good CR rate and very good disease free survival rate. However, the occurrence of severe, albeit limited, adverse effects suggests that this regimen should first be used in controlled therapeutic protocols to verify its efficacy with respect to less intensive approaches.

Adult↗
PubMed1997

Aberrant, noninfectious HIV-1 particles are released by chronically infected human T cells transduced with a retroviral vector expressing an interfering HIV-1 variant.

The expression of the nonproducer F12-HIV-1 genome has been previously shown to protect the host cell from HIV superinfection. In order to estimate the efficacy of the F12-HIV genome as an anti-HIV reagent also in cells already infected, an HIV-1 chronically infected Hut-78 cell clone (D10) was superinfected with an amphotropic mouse/human pseudotype retrovirus whose genome expresses both the F12-HIV genome and the selection marker gene (i.e. the c-DNA of a truncated form of the nerve growth factor receptor, NGFr) under the control of F12-HIV 5'LTR. D10 cells homogenously expressing the F12-HIV genome (T-D10) released unaltered amounts of retrovirions whose infectivity was, however, dramatically impaired (from 9 x 10(3) in D10 to < 10(0.5). TCID50/ml in T-D10 supernatants). Electron microscopy showed that the morphology of retrovirions released by T-D10 cells was heavily altered, both in size and shape. Furthermore, no retrotranscription products were detectable in CD4 cells challenged with T-D10 retrovirions. For the first time, the block in the infectivity of HIV released from already infected cells through the expression of an anti-HIV retroviral vector was demonstrated. These data could have important implications both from a perspective of F12-HIV-based anti-HIV gene therapy and, in general, on the role that nonproducer and/or defective HIV could play 'in vivo' in HIV infection and AIDS pathogenesis.

Cell Culture Techniques↗
PubMed1997

Stable transfection of provirus of human immunodeficiency virus into a murine packaging cell line.

In order to generate HIV (murine leukemia virus (MuLV)) pseudotypes, HIV genome was transfected into the ecotropic murine packaging cell line (GP+E86) and four of the nine transfected clones were extensively characterized. One clone (801), harbouring a full copy of integrated HIV sequences, exhibited a detectable level of intracellular HIV p24 antigen expression. Northern blot analysis revealed that clone 801 expressed all three classes of HIV mRNAs. Multispliced 2 kb mRNAs were detected in another clone (8.14). Two other clones (1.31 and 1.32) also exhibited a complete HIV provirus, but did not show any viral expression, as evaluated by Northern blot analysis or HIV p24 ELISA. Reverse transcription-polymerase chain reaction (RT-PCR) experiments revealed the presence of full length genomic RNA in four transfected clones, which were extensively characterized. A co-cultivation of clone 801 with human CD4' cells resulted in syncytia formation. By electron microscopy, mature HIV particles were observed after co-cultivation of uninfected C8166 cells with 801 cells. These results demonstrated that the murine clone was stably transfected with the complete HIV genome and was capable of shuttling infectious HIV to human cells. Clone 801 was co-cultivated with murine NIH-3T3 fibroblasts. In several experiments, HIV infection of NIH-3T3 cells was revealed by PCR technique. Thus, 801 cells appear to produce low levels of HIV (MuLV) pseudotypes capable of transferring the HIV genome into mouse cells.

3T3 Cells↗
PubMed1996

Sensitive detection of circulating breast cancer cells by reverse-transcriptase polymerase chain reaction of maspin gene.

BACKGROUND: Maspin, a recently identified protein related to the family of serpins, is believed to play a role in human breast cancer. In an effort to improve the present methods of detection, we have developed a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for maspin transcript to identify small numbers of mammary carcinoma cells in the peripheral blood and bone marrow of patients with breast cancer. PATIENTS AND METHODS: Five non-neoplastic mammary tissue samples, 13 breast cancer specimens as well as 17 peripheral blood and 4 bone marrow samples from normal subjects were screened for the presence of maspin mRNA by RT-PCR. The same assay was applied to peripheral blood or bone marrow samples obtained from 29 patients with stages I to IV breast cancer. RESULTS: By RT-PCR it was possible to amplify maspin mRNA in all of the primary and metastatic breast cancer specimens, but in none of the normal hemopoietic samples from healthy donors. Thus, detection of maspin transcript in the peripheral blood or marrow of a patient known to have breast cancer is indicative of the presence of mammary carcinoma cells. In reconstitution experiments, maspin RT-PCR reliably detected 10 mammary carcinoma cells in 1 million normal peripheral-blood mononuclear cells (PBMCs). None of the 9 patients with stages I, II, or III breast cancer had maspin transcript in peripheral blood. Of note, 3 of 9 patients with stage IV breast cancer receiving systemic therapy at the time of sample collection, but only 1 of 11 patients with stage IV not receiving therapy, had detectable maspin transcript in peripheral blood. Moreover, 3 marrow specimens from stage IV patients tested positive by this assay. CONCLUSIONS: This pilot study suggests that maspin RT-PCR assay is a sensitive, specific and sufficiently rapid method for detection of small numbers of circulating cells and marrow micrometastases in breast cancer patients. The possibility of applying this assay in the detection of tumor cell contamination of both marrow and stem-cell apheresis harvests of breast cancer patients merits further investigation.

Breast Neoplasms↗
PubMed1996

The non-producer phenotype of the human immunodeficiency virus type 1 provirus F12/HIV-1 is the result of multiple genetic variations.

A cell clone (Hut-78/F12) chronically infected with a non-producer human immunodeficiency virus type 1 (HIV-1) variant showed an abnormal pattern of virus structural proteins and released no detectable virus particles. Exchanges of homologous parts of the F12/HIV provirus and a replication-competent HIV (strain NL4-3) were undertaken to define the genetic determinants of the F12/HIV phenotype. The non-infectious phenotype was reproduced by replacing an NL4-3 genomic fragment encoding the C terminus of gp 120 and the N terminus of gp41 with the corresponding parts of the F12/HIV provirus. Conversely, a much more extended genomic fragment (encompassing the vif, pol and env genes) was necessary to convert the F12/HIV phenotype. These results demonstrate that the F12/HIV non-producer phenotype is the result of mutations scattered along most of the genome, rendering the conversion to an infectious phenotype a very unlikely event. The F12/HIV genome is thus a reliable model for preclinical studies of anti-HIV gene therapy.

Defective Viruses↗
PubMed1996

Anti-HIV viral interference induced by retroviral vectors expressing a nonproducer HIV-1 variant.

A Hut-78 cell clone (F12) harboring a nonproducer human immunodeficiency virus (HIV-1) variant shows complete resistance to HIV-1 or HIV-2 superinfection. The F12-HIV provirus produces an altered HIV-1 protein pattern and cannot generate even immature viral particles. We demonstrated that HeLa CD4+ cells transfected with the F12-HIV genome resist HIV superinfection through a CD4-independent mechanism. As F12-HIV appears to be a useful system to induce anti-HIV intracellular immunization, we constructed various retroviral vectors containing the F12-HIV genome, modified by elimination of the F12 3'LTR and part of its nef gene, inserted 'antisense' with respect to the Moloney murine leukemia virus 5' LTR. Here we show that recombinant retroviral particles carrying the N2/F12-HIV nef- (as) construct can stably transduce both CEMss human cells and primary human peripheral blood lymphocytes, inducing the expression of the F12-HIV genome. These results could open the way to an anti-AIDS gene therapy strategy based on F12-HIV-induced intracellular immunization.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Vinblastine, bleomycin, and methotrexate chemotherapy plus extended-field radiotherapy in early, favorably presenting, clinically staged Hodgkin's patients: the Gruppo Italiano per lo Studio dei Linfomi Experience.

PURPOSE: To ascertain whether vinblastine, bleomycin, and methotrexate (VBM) (CT) combined with extended-field radiotherapy (EF RT) is effective enough to spare laparotomy in early, favorably presenting Hodgkin's disease (HD) patients. PATIENTS AND METHODS: Fifty patients with clinical stage IA or IIA HD with favorable histology and no bulky masses entered a prospective multicenter study started in January 1988. The median follow-up time was 38 months. RESULTS: All patients achieved a complete remission (CR). Five relapsed after 3 to 40 months and underwent successful salvage therapy. The actuarial remission rate was 0.89% at 3 years and 0.82% at 5 years. Two patients died in CR: one of severe pulmonary toxicity, the other of a second neoplasia (adenocarcinoma of the lung), 2 and 43 months after the end of therapy, respectively. The hematologic toxicity recorded during VBM CT was mild on the whole. Major toxicity was represented by pulmonary side effects and neurologic symptoms. Multiple regression analysis demonstrated that pulmonary toxicity was significantly related only to the amount of RT delivered to the mediastinum and not to the relative dose of bleomycin, to the dose-intensities of the three drugs in the regimen, or to patient age or sex. The same statistical technique showed that the only clinical factor related to grade of neurotoxicity was vinblastine dosage. CONCLUSION: VBM CT combined with EF RT is an effective treatment for early, clinically staged, favorable HD patients. However, the toxicity of this combination suggests that certain modifications should be evaluated.

Adolescent↗