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M Spina

Publications and source records attributed to M Spina.

At least 37 records · Page 2Linked to original sources
PubMed2001

Human immunodeficiency virus-related non-Hodgkin lymphoma: activity of infusional cyclophosphamide, doxorubicin, and etoposide as second-line chemotherapy in 40 patients.

BACKGROUND: The prognosis of patients with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL) is poor. In fact, despite a high complete response (CR) rate, approximately 50% of these patients die from progressive lymphoma. METHODS: From November 1994 to April 2000, the authors treated 40 patients with resistant or recurrent HIV-related NHL with a 96-hour continuous intravenous infusion of cyclophosphamide (187.5 mg/m(2) per day), doxorubicin (12.5 mg/m(2) per day), and etoposide (60 mg/m(2) per day). RESULTS: The median number of cycles administered was two (range, one to six cycles). A CR was documented in 4 of 40 patients (10%), and a partial remission (PR) was documented in 7 of 40 patients (18%). The CR median duration was 6 months (range, 4--30+ months), whereas PRs lasted for 5 months (range, 2--8 months). The overall median survival was 4 months (range, < 1--33 months), and the median survival for responding patients was 10 months. CONCLUSIONS: The current data confirm that infusional cyclophosphamide, doxorubicin, and etoposide is active in patients with refractory or recurrent HIV-related NHL. However, the median survival of these patients remains poor, and the other innovative approaches should be used.

Adolescent↗
PubMed2001

Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924.

PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high-dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was.009; and for the overall response, it was.06. There was no statistically significant difference in survival (P =.122) or time to progression (P =.114). Progression-free survival was significantly better with HD-MVAC (P=.037; hazard ratio.75; 95% CI.58 to.98). The median progression-free survival time was 9.1 months on the HD-MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free survival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% CI, 5.9% to 17.4%). CONCLUSION: With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.

Adult↗
PubMed2001

Concomitant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy plus highly active antiretroviral therapy in patients with human immunodeficiency virus-related, non-Hodgkin lymphoma.

BACKGROUND: The feasibility and efficacy of concomitant chemotherapy and highly active antiretroviral therapy (HAART) is still unknown in patients with human immunodeficiency virus (HIV)-related malignancies. To evaluate the impact of chemotherapy plus HAART on the clinical course of patients with HIV-related, systemic, non-Hodgkin lymphoma (HIV-NHL), the authors compared retrospectively a group of 24 patients with HIV-NHL who were treated with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen plus HAART with a group of 80 patients who were treated with CHOP chemotherapy or a CHOP-like regimen (i.e., cyclophosphamide, doxorubicin, teniposide, and prednisone with vincristine plus bleomycin) without receiving antiretroviral therapy. METHODS: All patients were enrolled in two sequential trials performed at the Aviano Cancer Center, Italy, from April 1988 to December 1998. HAART was included with combination therapy from January 1997. Antiretroviral regimens consisted of two reverse transcriptase inhibitors and one protease inhibitor. RESULTS: The two treatment groups were well matched with regard to patient demographics, NHL characteristics, HIV status, and treatment, i.e., the number of cycles and chemotherapy dose. The response rates were similar between the two groups. Severe anemia (Grade 3-4 according to the World Health Organization criteria) was significantly greater in the patients who received CHOP-HAART compared with the patients who received CHOP alone (33% vs. 7%, respectively; P = 0.001). Leukopenia was similar between the two groups, but colony stimulating factor support was significantly greater in the CHOP-HAART group than in the control group (92% vs. 66%, respectively; P = 0.03). Seventeen percent of CHOP-HAART patients developed severe autonomic neurotoxicity, whereas none of the CHOP patients developed neurotoxicity (P = 0.002). At similar median follow-up, opportunistic infection (OI) rates and mortality were significantly lower in the CHOP-HAART patients than in the CHOP patients (18% vs. 52%, respectively; P = 0.05; and 38% vs. 85%, respectively; P = 0.001). The median survival for CHOP-HAART patients was not reached, whereas the medial survival of CHOP patients was 7 months (P = 0.03). CONCLUSIONS: The combination of CHOP plus HAART is feasible and may reduce the morbidity from OIs in HIV-NHL patients. However, careful attention must be directed to cross toxicity and possible pharmacokinetic interactions between antiretroviral and antineoplastic drugs. The impact of the combined chemotherapy plus HAART treatment on patient survival needs urgently to be evaluated in prospective studies.

AIDS-Related Opportunistic Infections↗
PubMed2001

Lymphocyte subsets and viral load in patients with HIV-associated non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibody and chemotherapy.

The anti-CD20 monoclonal antibody Rituximab is a novel antitumor agent used in association with chemotherapy (CT) for the treatment of high-grade/intermediate non-Hodgkin's lymphomas (NHL) in HIV-negative populations. This therapeutic combination is currently also being explored in HIV-positive patients with NHL (HIV-NHL). The objective of our study was to determine CD4 and CD8T cell counts, HIV plasma viremia and proviral load in patients with CD20-positive HIV-NHL treated with Rituximab plus CT and highly active antiretroviral therapy (HAART). We studied eight patients with HIV-NHL treated by anti-CD20 and CT before, after three, and after six cycles of therapy; CD4, CD8 and CD19 lymphocyte subsets were measured by monoclonal antibodies and flow cytometry. HIV plasma viremia was determined by the b-DNA assay, and proviral load by a quantitative competitive PCR. CD4T cell counts remained stable after three cycles of therapy, while a significant reduction of this subset was present at the end of therapy. HIV plasma viremia was significantly reduced after the third cycle, but returned to pretreatment levels at the end of therapy; we also observed individual fluctuations of proviral load during therapy, this marker being increased in two out of three patients at the end of therapy. These observations suggest that Rituximab plus CT accelerated the rate of CD4 depletion and of HIV replication in the peripheral blood of HIV-NHL patients and that HAART may be able to delay these effects.

Adult↗
PubMed2001

Clinical aspects and management of Hodgkin's disease and other tumours in HIV-infected individuals.

As the AIDS epidemic advances, the spectrum of malignancies encountered is expanding. Several non-AIDS defining cancers, i.e. Hodgkin's disease (HD), anal and testicular cancer, are increasing in incidence in HIV-infected patients. The widespread use of highly active antiretroviral therapy (HAART) in industrialised countries has resulted in substantial improvement in the survival of HIV-infected patients. It is likely that in the future, cancers associated with long-term mild immune suppression will occur at an increased rate in long-term survivors of HIV infection. The natural history of the majority of non-AIDS defining tumours differs from that of the general population. Unusual aspects of tumour localisation, growth behaviour and therapeutical responses distinguish tumours in patients with HIV infection from those without. This paper reviews the most relevant data on the epidemiology, pathology, clinical features and treatment of the most frequently reported non-AIDS defining tumours, i.e. HD, lung, testicular and skin cancers.

Adult↗
PubMed2001

Combined treatment with high-dose methotrexate, vincristine and procarbazine, without intrathecal chemotherapy, followed by consolidation radiotherapy for primary central nervous system lymphoma in immunocompetent patients.

OBJECTIVES: To assess the feasibility and the activity, as well as the efficacy to treat meninges, of chemotherapy (CHT) containing high-dose methotrexate (HD-MTX) followed by radiation therapy (RT), without intrathecal CHT, in patients with primary central nervous system lymphoma. METHODS: Eligibility criteria were histologically proven diagnosis, disease limited to the CNS, age < or = 70, ECOG performance status < or = 3, HIV-negative and no prior treatment. Thirteen patients (1996-1999; median age 54 years) received two courses of vincristine 1.4 mg/m2 day 1, MTX 3 g/m2 days 3 and 10 and procarbazine 100 mg/m2 days 1-14 every 4 weeks. Patients who achieved a complete remission were referred to RT, those with progressive disease were excluded from further study; all the remaining patients received a third course of CHT followed by RT. RESULTS: Twelve patients responded to CHT (overall response rate = 92%, complete response rate = 77%): 9 underwent consolidation RT, 3 did not. Two patients experienced severe acute toxicity; lethal pulmonary thromboembolism and transient renal failure. Five patients relapsed: 2 after CHT and 3 after RT. Relapse was local in all cases, with a case of concomitant hepatic involvement. No cases of ocular or meningeal relapse were observed. In contrast to high-dose cytarabine-containing CHT, salvage therapy with temozolomide produced good results. Two patients died of treatment-related neurotoxicity. Six patients are alive with a median follow-up of 17 months, and a 2-year overall survival (OS) of 61%. The median survival of the 9 patients who completed the planned treatment is 25+ months with a 2-year OS of 80%. CONCLUSIONS: HD-MTX, procarbazine and vincristine followed by RT, without intrathecal therapy, produce similar results with respect to other HD-MTX-containing regimens. These results seem to suggest that adequate meningeal treatment is possible without intrathecal drug delivery, even in CSF-positive patients. Corroborating data from a larger series are, however, necessary. Temozolomide should be tested in relapsed patients in a phase II prospective trial.

Adult↗
PubMed2001

[Systemic HIV-non-Hodgkin lymphoma in the era of HAART. Natural history].

In the era of highly active antiretroviral therapy (HAART), systemic non-Hodgkin lymphoma (NHL) represented the most frequent cancer associated to HIV infection. In contrast to Kaposi's sarcoma and primary central nervous system lymphoma (PCNSL) which incidence have been declining after introduction of HAART, systemic NHL-HIV has relatively stable remained. Systemic HIV related NHL are markedly heterogeneous both histologically and clinically and this clinicophatological heterogenity reflects variability in the molecular lesions associated to these lymphomas and immunological status of these patients. The introduction of HAART has substantially modified the approach to HIV related lymphomas. The results of recent monoinstitutional study of Aviano Cancer's Institute on 235 patients have suggested that HAART would otherwise allow a long life expectancy with longer disease free survival and overall survival. In fact the reduced of morbidity of AIDS patients bought by HAART justified the use of aggressive antineoplastic therapies.

Adult↗
PubMed2000

Lung carcinoma in 36 patients with human immunodeficiency virus infection. The Italian Cooperative Group on AIDS and Tumors.

BACKGROUND: The current study describes the clinicopathologic characteristics of 36 patients with lung carcinoma and human immunodeficiency virus (HIV) infection observed within the Italian Cooperative Group on AIDS and Tumors (GICAT). METHODS: Patients with lung carcinoma and HIV infection collected by the GICAT between 1986-1998 were evaluated retrospectively. As a control group, the authors analyzed 102 patients age < 60 years with lung carcinoma but without HIV infection who were seen at the CRO, National Cancer Institute, Aviano, Italy between 1995-1996. RESULTS: Patients with lung carcinoma and HIV infection were younger (38 years vs. 53 years) and previously smoked more cigarettes per day (40 vs. 20) than the control group. The main histologic subtype was adenocarcinoma. TNM Stage III-IV disease was observed in 53% of the patients. The median CD4 cell count was 150/mm(3). The median overall survival was significantly shorter in the patients with HIV compared with the control group (5 months vs. 10 months; P = 0.0001). CONCLUSIONS: The results of the current study demonstrate that lung carcinoma in the HIV setting affects mainly young individuals with a history of heavy tobacco smoking and a moderately advanced immunodeficiency status. Lung carcinoma is associated with a more adverse outcome in HIV patients and represents the cause of death in the majority of these patients.

Adenocarcinoma↗
PubMed2000

Characterisation of elastin and collagen in aortic bioprostheses.

Porcine aortic valves used as cardiac valve bioprostheses are well adapted to physiological functions in the short term, but they lack long-term durability. Several multi-step extractions have been performed to obtain a perfectly acellular matrix. A new physical methodology is proposed to evaluate the resulting fibrous protein damage after biochemical extraction (TRI-COL and SDS). Thermal analysis techniques are adapted to collagen and elastin characterisation in the solid state. The aortic tissue thermal transitions are determined by differential scanning calorimetry (DSC): elastin glass transition is observed around 200 degrees C, and collagen denaturation is observed around 230 degrees C. These parameters are characteristic of the elastin network arrangement and of collagen triple-helix stability. The technique of thermostimulated currents (TSC) is well suited to specify the chain dynamics of proteins. The low-temperature relaxations observed in both collagen and elastin are associated with localised motions, whereas the high-temperature modes are attributed to more delocalized motions of the chains. Therefore TSC and DSC spectrometries allow physical parameters specific to collagen and elastin to be obtained and their interaction in aortic tissues to be determined. According to the significant evolution of these parameters on SDS samples, the destabilizing effect of this detergent is highlighted.

Animals↗
PubMed2000

Dielectric characterization of collagen, elastin, and aortic valves in the low temperature range.

The low temperature dielectric relaxation of porcine aortic valves and its main macromolecular proteins. i.e. elastin and collagen, have been investigated in the dry state and at low levels of hydration by thermally stimulated currents spectrometry, with an equivalent frequency of 10(-3) Hz. Two secondary relaxation modes, labeled gamma and beta with increasing temperature, are found for the three materials. Since the gamma-mode is independent upon hydration while the beta-mode is strongly plasticized by water, these relaxation modes have been attributed to localized motions of the polypeptidic chains containing apolar and polar residues, respectively. The deconvolution of the beta-mode by fractional polarization gives the experimental distribution of the dielectric relaxation times of the three materials, and allows us to deduce the activation parameters of each elementary process. These analyses shows the existence of compensation phenomena between the activation parameters, implying cooperative mechanisms. The occurrence of these phenomena with their characteristic parameters are used to specify the origin of the localized relaxation modes in collagen and elastin, and to assign the specific role of each protein in the aortic valves.

Animals↗
PubMed2000

Human immunodeficiency virus-associated Hodgkin's disease.

Hodgkin's disease represents the most common type of non-acquired immunodeficiency virus (AIDS)-defining tumor that occurs in the human immunodeficiency virus (HIV)-positive population. More than 300 cases of Hodgkin's disease in HIV-infected individuals have been reported, mainly from the European countries (ie, Italy, Spain, and France) and to a lesser extent from the United States. All series have documented unusually aggressive tumor behavior, including a higher frequency of unfavorable histologic subtypes, advanced stages, and poorer therapeutic outcome, as compared with the behavior of Hodgkin's disease outside of the HIV setting.

Hodgkin Disease↗
PubMed1999

Thermal analysis characterization of aortic tissues for cardiac valve bioprostheses.

Two multistep extractions were achieved on porcine aortic tissues to obtain acellular matrices used for cardiac bioprostheses. The evaluation of structural modifications and the possible damage of extracellular matrix fibrous proteins were investigated by means of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Protein-water interactions and degradation temperatures were determined by TGA. DSC was used to characterize protein thermal transitions (glass transition and denaturation), which provided information on the dynamic structure of the aortic tissue components. Sodium dodecyl sulfate (SDS) extraction had a destructuring effect, while Triton and cholate treatments did not affect the structural integrity of either elastin and collagen. A DSC comparison showed that SDS destabilizes the collagen triple helical domain and swells the elastin network.

Absorption↗
PubMed1999

Structural and compositional determinants of cortistatin activity.

Cortistatin-14 (CST-14) is a putative novel neuropeptide that shares 11 of its 14 residues with somatostatin-14 (SRIF-14), yet its effects on sleep physiology, locomotor behavior and hippocampal function are different from those of somatostatin. We studied the structural basis for cortistatin's distinct biological activities. As with SRIF-14, CST-14 does not show any preferred conformation in solution, as determined by circular dichroism and nuclear magnetic resonance. Synthetic cortistatin analogs were designed and synthesized based on the cyclic structure of octreotide. Biological assays were carried out to determine their binding affinities to five somatostatin receptors (sstl-5) and their ability to produce changes in locomotor activity and to modulate hippocampal physiology and sleep. The results show that the compound with N-terminal proline and C-terminal lysine amide exhibits cortistatin-like biological activities, including reduction of population spike amplitudes in the hippocampal CA1 region, decrease in locomotor activity and enhancement of slow-wave sleep 2. These findings suggest that both proline and lysine are necessary for cortistatin binding to its specific receptor.

Amino Acid Sequence↗
PubMed1999

Physicochemical properties of arterial elastin and its associated glycoproteins.

Microfibrillar glycoproteins are a significant component of vascular elastic tissue, but little is known about their contribution to vascular physiology and pathology. We have investigated some physicochemical properties of the glycoproteins that may be pertinent to these roles. Because of the difficulty in isolating intact glycoproteins in a form and quantity suitable for physicochemical examination, we based our analysis on a comparison of the properties of porcine thoracic aorta and pulmonary artery extracted with GuHCl and collagenase (preparation GC) and after further treatment with dithioerythritol to remove glycoproteins (preparation GC/DTE). Amino acid analysis showed that GC/DTE had the amino acid composition of pure elastin while GC contained a higher proportion of polar amino acids, particularly in the aortic preparation. GC stained with alcian blue, particularly in the intimal region, but GC/DTE did not. GC had a higher water content and a slower viscoelastic response and the circumferential elastic modulus was approximately 50% lower (whether expressed in terms of sample weight or elastin content). Clearly, therefore, the microfibrils do not stiffen the network and may prevent the alignment of elastin fibers in the circumferential direction. Their effect on hydration may arise either because they impose mechanical constraints on the geometry of the network or because they modify the inter- and intramolecular hydrophobic or electrostatic interactions that influence the tissue organization and hydration. Molecular probe measurements of the intrafibrillar pore structure using radiolabeled and fluorescent probes showed that removal of the microfibrils caused a slight decrease in the extrafibrillar water space and a larger decrease in the intrafibrillar water space. Sucrose, a small probe molecule, was able to penetrate most of the intrafibrillar water space when microfibrils were present but was virtually excluded when they were not. Potentiometric titration and radiotracer assays of ion binding both showed that the microfibrils contribute a considerable negative charge (-9 mumoles/g wet tissue in the aortic preparation and -16 mumoles/g wet weight in the pulmonary artery) and increase calcium binding by approximately 30%.

Animals↗
PubMed1999

Corticotropin-releasing factor antagonist attenuates the "anxiogenic-like" effect in the defensive burying paradigm but not in the elevated plus-maze following chronic cocaine in rats.

RATIONALE: Chronic cocaine abuse is associated with the development of anxiogenic states in humans. Corticotropin-releasing factor (CRF) is an endogenous neurotropic factor well known to modulate stress responses. It has been postulated that CRF is involved in the neurobiological mechanisms underlying the anxiety and/or stress responses associated with removal of cocaine after chronic administration. OBJECTIVE: The present study investigated the role of endogenous CRF in mediating the "anxiety-like" effect 48 h after the cessation of saline or chronic cocaine treatment in rats, using the defensive burying paradigm and the elevated plus-maze. METHODS: Rats received daily injections of cocaine (20 mg/kg IP, for 14 consecutive days) or vehicle. Forty-eight hours after the last injection, animals were tested in the plus-maze and then in the defensive burying paradigm. In a second experiment, intracerebroventricular (ICV) cannulae were implanted at the lateral ventricle. Animals were allowed a 1-week period for recovery before starting the chronic drug treatment. The defensive burying testing took place 48 h after cessation of the treatment. The CRF antagonist [DPhe12, Nle21,38, CalphaMe Leu37] r/h CRF(12-41), (also known as D-phe CRF(12-41)) (0.04, 0.2 and 1.0 microg/5 microl) was injected 5 min before the 15-min testing. RESULTS: An "anxiogenic-like" effect following chronic cocaine treatment was demonstrated with the defensive burying paradigm, but not with the elevated plus-maze. This "anxiety-like" response was attenuated by ICV pretreatment with the CRF antagonist D-Phe CRF(12-41), with the highest dose of the CRF antagonist reversing the observed "anxiogenic-like" response. CONCLUSIONS: These data suggest that brain CRF may be substantially involved in the development of "anxiety-like" responses related to cocaine withdrawal and could be important for future drug dependence treatments.

Animals↗