PET-adapted therapy after three cycles of ABVD for all stages of Hodgkin lymphoma: results of the GATLA LH-05 trial.

The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I-IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3-negative patients received no further therapy.

Dynamic switching of a packaged photonic integrated network-on-chip using an FPGA controller.

A packaged photonic integrated network-on-chip (NoC) based on multi-microrings with a controller and scheduler implemented in FPGA is demonstrated under dynamic packet-switched traffic. Multiple transmission scenarios have been investigated, comprising up to three interfering signals at the same wavelength. The dynamic switching exhibits a power penalty of approximately 0.

Experimental demonstration of a 24-port packaged multi-microring network-on-chip in silicon photonic platform.

A 24-port packaged multi-microring optical network-on-chip has been tested for simultaneous co- and counter-propagating transmissions at the same wavelength at 10 Gbps. In the co-propagating scenario communications up to five hops with one interfering signal have been tested, together with transmissions impaired by up to three interfering signals. In the counter-propagating scenario the device performance has been investigated exploiting the ring resonators in both shared-source and shared-destination configurations.

BER evaluation of a low-crosstalk silicon integrated multi-microring network-on-chip.

The operation of an integrated silicon-photonics multi-microring network-on-chip (NoC) is experimentally demonstrated in terms of transmission spectra and bit error rates at 10 Gb/s. The integrated NoC consists of 8 thermally tuned microrings coupled to a central ring. The switching functionalities are tested with concurrent transmissions at both the same and different wavelengths.

Silicon-based all-optical multi microring network-on-chip.

An optical multi microring network-on-chip (MMR NoC) is proposed and evaluated through numerical simulations. The network architecture consists of a central resonating microring with local microrings connected to the input/output ports. A mathematical model based on the transfer matrix method is used to assess the MMR NoC performance and to analyze the fabrication tolerances.

Risk-adapted therapy with three or six cycles of doxorubicin/bleomycin/vinblastine/dacarbazine plus involved-field radiation therapy in Hodgkin lymphoma, based on prognosis at diagnosis and early response: results from the GATLA study.

Background: Doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) plus involved-field radiation therapy (IFRT) is the gold-standard treatment for early and advanced stages of Hodgkin lymphoma (HL). We evaluated the outcomes of patients according to prognosis at diagnosis and over time to determine who achieved complete remission (CR).

Patients And Methods: Treatment-naive patients under the age of 75 years at all stages of HL were eligible.

A transgenic mouse model engineered to investigate human brain-derived neurotrophic factor in vivo.

Brain-derived neurotrophic factor (BDNF) is an attractive component for the treatment of various neurodegenerative diseases such as Alzheimer's or Parkinson's disease. Innovative non-invasive therapeutic approaches involve appropriate pharmacological induction of endogenous BDNF synthesis in brain. A transgenic mouse model has been established to study human BDNF gene expression and permit the screening of compounds capable of stimulating its activity.

Is embryo-cryopreservation really neutral? A new long-term effect of embryo freezing in mice: protection of adults from induced cancer according to strain and sex.

Background: Beneficial or harmful effects of embryo freezing have been described in man and animals, raising the question of the neutrality of this technique.

Objective: We examined, in mice, the possibility that embryo freezing influences the probability of the emergence, in adults, of an induced urinary bladder cancer.

Methods: The experiment was conducted in mice derived from embryos of two different genotypes.

Autologous stem cell transplantation for patients with chronic myeloid leukemia. The Argentine Group of Bone Marrow Transplantation (GATMO) experience.

Background: The objective of this analysis was to evaluate the role of autologous stem cell transplantation (ASCT) in prolonging disease free survival (DFS) and overall survival (OS) in patients with chronic myeloid leukemia (CML) who received autografts of Philadelphia chromosome (Ph) positive or Ph negative cell harvests.

Methods: Over a 4-year period (1994-1999), 53 patients who underwent ASCT for CML were reported to the Argentine Group of Bone Marrow Transplantation (GATMO) Registry.

Results: Ph negative cell products were harvested in only 18 patients (34%).

Cyclophosphamide-immunodepressed FVB/N mice: potentiating the effects of testicular cytomegalovirus infection.

The aim of this study was to investigate the effect of cyclophosphamide (CY) immunosuppression on the infection of germinal cells following testicular inoculation of male FVB/N mice with murine cytomegalovirus (MCMV). We used CY to modulate the immune status in order to mimic iatrogenic immunosuppression in humans (organ transplantation) as closely as possible. We show that viral pathological manifestations observed in mice treated with this CY-MCMV combination were severer than those observed in immunocompetent male mice infected with MCMV alone.

Failure to infect embryos after virus injection in mouse zygotes.

Background: The intracytoplasmic injection of sperm raises the problem that viral elements may be transported into the oocyte by the spermatozoon or the surrounding medium. It also raises questions about how the developing zygote will behave.

Methods: We used the murine model to microinject murine cytomegalovirus (MCMV) into the zygote ooplasm and followed the changes in these microinjected zygotes in vivo and in vitro over time.

Experimental inoculation of male mice with murine cytomegalovirus and effect on offspring.

Background: Murine cytomegalovirus (MCMV) was used to examine aspects of viral infection in male mice, and its possible transmission to their offspring.

Methods And Results: FVB/N mice inoculated intratesticularly with 5x10(5) plaque forming units (PFU) of MCMV, developed peritoneal haemorrhagic exudates, spleen hypertrophy and acute local infection. Infectiousness was detected until 15 days post-inoculation (D15 PI) in the genital organs, and virus DNA up to D35 PI.

Identification of pancreatic type I secreted phospholipase A2 in human epidermis and its determination by tape stripping.

Phospholipases A2 (PLA2) catalyse the release of fatty acids from the sn-2 position of phospholipids and have been suggested to play a key part in permeability barrier homeostasis. Using a sensitive and versatile fluorometric method, significant PLA2 activity has been detected in both human skin homogenates and tape strippings of stratum corneum. Based on various properties (resistance to heat and sulphuric acid treatment, neutral optimal pH, absolute requirement for millimolar calcium concentrations, inhibition by dithiothreitol and p-bromophenacyl bromide, and resistance to a trifluoromethyl ketone derivative of arachidonic acid, AACOCF3, a specific inhibitor of cytosolic PLA2), this enzyme was characterized as a secretory PLA2 (sPLA2).

Testicular wild-type p53 expression in transgenic mice induces spermiogenesis alterations ranging from differentiation defects to apoptosis.

While p53 is dispensable for development, an excess of p53 has dramatic consequences on the embryogenesis and on the cell differentiation. In an attempt to analyse in vivo the effects of p53 activity, we have generated transgenic mice expressing the wild-type p53 under the control of the metallothionein I promoter. In the three transgenic lines established, exogenous p53 is expressed constitutively in the postmeiotic cells of transgenic males and two lines are subfertile.

Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease.

Purpose: To evaluate in a randomized trial the impact of three versus six cycles of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) chemotherapy in favorable-prognosis and CVPP versus doxorubicin, vincristine, prednisone, and etoposide (AOPE) plus involved-field radiotherapy (RT) in intermediate-prognosis previously untreated Hodgkin's disease.

Patients And Methods: Of 256 patients evaluated, 80 with a favorable prognosis according to a prognostic index designed by the Grupo Argentina de Tratamiento de Leucemia Aguda (GATLA) were randomized to three versus six cycles of CVPP without RT and 176 with intermediate risk to CVPP versus AOPE, both for six cycles with RT between the third and fourth cycles of 30 Gy to the involved areas at diagnosis. CVPP consisted of intravenous (I.

Multivariate analyses of prognostic factors associated with hematopoietic recovery in autograft patients with different sources of progenitor cells. A GATMO experience. Argintine Group of Bone Marrow Transplant.

Objective: To evaluate in a multivariate analysis the prognostic factors associated with hematopoietic recovery and the supportive care requirements after autotransplant of progenitor cells (PC) from various sources: bone marrow (BMPC), BMPC & peripheral blood (PBPC), and PBPC alone.

Patients And Methods: A total of 570 patients with hematological malignancies and solid tumors underwent high-dose therapy followed by autotransplant. PBPC were obtained after mobilization with chemotherapy and/or cytokines.

Developmental control of IFN-alpha expression in murine embryos.

The expression of IFN-alpha transcripts was investigated in murine embryos, fetuses, and fetal annexes in mid and late pregnancy. We have shown by Northern blot analysis, reverse transcription-polymerase chain reaction, and in situ hybridization the presence of IFN-alpha transcripts in mouse placenta, fetus, and newborn. From the 14th day of gestation until birth, a typical IFN-alpha transcript (1.

Results of treatment with an intensive combination induction regimen containing idarubicin in children with acute myeloblastic leukemia: preliminary report of the Argentine Group for Treatment of Acute Leukemia.

In April 1990, the Argentine Group for Treatment of Acute Leukemia began a multicenter trial for the treatment of previously untreated acute myeloblastic leukemia patients who were under 21 years of age. Initial treatment consisted of an 8-day induction phase with cytarabine together with idarubicin on days 3 to 5 and etoposide on days 6 to 8. A multidrug consolidation phase was subsequently administered and, after a treatment-free interval of 2 to 4 weeks, two 5-day intensification courses with high-dose cytarabine and etoposide were delivered with a 4-week interval between each course.

[Comparative study of 1st generation versus 2d generation (CAVPE) combinations in intermediate and high-grade lymphomas].

Purpose: To compare four first generation chemotherapy regimes (FGR) used by GATLA in low and intermediate grade lymphomas. Versus a second generation regimen called CAVPE.

Patients And Methods: A group of 205 patients treated with FGR (79 with BACOP, 89 with COPP, 19 with CHOP, and 18 with CNOP), and 244 others treated with the combination of cyclophosphamide, doxorubicin, vincristine, prednisone and etoposide (CAVPE) were included.

Enhancement by stable butyrate derivatives of antitumor and antiviral actions of interferon.

The use of n-butyric acid has been associated with induction of cell differentiation and bypassing of genetic defects in the suppression of malignancy. This biological response modifier satisfies the requirements for specificity and low toxicity, and its use can be considered as an alternative approach to conventional cancer chemotherapy. However, a lack of clinical efficacy has been observed with butyrate and attributed mainly to the rapid metabolism of the compound.

Pharmacokinetic studies of N-butyric acid mono- and polyesters derived from monosaccharides.

The pharmacokinetics of seven butyric esters derived from monosaccharides were studied after iv administration of a bolus dose to rabbits. Results obtained showed that a constant plasma level of butyric acid is maintained due to the slow disappearance of butyric acid esters from the plasma in contrast to the case of salts, such as arginine butyrate, which are rapidly cleared. The maintenance of these covalent compounds in the body can increase concentrations of n-butyric acid in the tumor area for more efficient chemotherapy.

[Protective activity of monoacetone glucose 3-butyrate, prodrug of n-butyric acid, against the fatal effect of encephalomyocarditis virus in mice].

A comparative study was made, in the mouse, on antiviral properties of a prodrug of n-butyric acid derived from monosaccharides: monoacetone glucose 3-butyrate (MAG = 3but), and of a free form of n-butyric acid: arginine butyrate (BuO Arg). Preventive injection of MAG = 3but protected the mice twice as effectively as BuO Arg against the lethal effect of 100 LD50 of encephalomyocarditis virus. Under the same experimental conditions, monoacetone glucose (MAG) used as carrier of the biologically active moiety, was inactive on its own.

Butyric monosaccharide ester-induced cell differentiation and anti-tumor activity in mice. Importance of their prolonged biological effect for clinical applications in cancer therapy.

The interest of butyric salts is based on their capacity to promote differentiation of malignant cells and inhibition of tumor development. The phenotypic modifications are rapidly reversible and require the continuous presence of butyric salts in the target area, which raises problems for therapeutic applications. We show here that the covalent binding of n-butyric acid on natural polyhydroxylated compounds such as monosaccharides, especially 3- or 6-O-butanoyl-1,2-O-isopropylidene-alpha-D-glucofuranose, retains the majority of the biological properties of n-butyric acid.

Low level toxicity and antitumor activity of butyric mono- and polyester monosaccharide derivates in mice.

This study compares the antitumor activity of five mono- and polyesters of n-butyric acid derived from monosaccharides in the murine model of Crocker 180 TG Sarcoma. Tumor incidence at ten days, mean survival time and final survival rate were significantly affected in all cases. Combined treatment by butyric esters, alpha/beta interferon (IFN) and/or Corynebacterium parvum used as immunestimulator improved the antitumor protection.