WPHACT 2.0 is the new fully massive version of a MC program and unweighted event generator which computes all Standard Model processes with four fermions in the final state at
e
+
e
− colliders. The ...program can now generate unweighted events for any subset of all four fermion final states in a single run, by making use of dedicated pre-samples which can cover the entire phase space. Improvements with respect to
WPHACT 1.0 include the Imaginary Fermion Loop gauge restoring scheme, new phase space mappings, a new input system, the possibility to compute subsets of Feynman diagrams and options for including ISR via
QEDPS, running
α
QED, CKM mixing, resonances in
q
q
̄
channels.
The aim of the present study was to investigate the effects of 5-aminosalicyclic acid (5-ASA) on the cell injury mediated by activated neutrophils. We used a system constituted of neutrophils, ...triggered with phorbol myristate acetate, and 51Cr-labelled Daudi cells as targets. The results show that 5-ASA is capable of efficiently preventing neutrophil-mediated lysis. 5-ASA was up to 10-fold more effective than taurine, which acts as an hypochlorous acid scavenger. Moreover, 5-ASA was found to compete with taurine for the neutrophil derived hypochlorous acid. The results are consistent with the conclusion that 5-ASA is capable of limiting the neutrophil mediated cell damage by scavenging the generated hypochlorous acid. This may represent a potential mechanism for the therapeutic action of 5-ASA in ulcerative colitis.
We propose a new helicity formalism based on the insertion in spinor lines of a complete set of states built up with appropriate unphysical spinors, which are eigenstates of
▪, where
p is the ...momentum flowing in a fermion propagator. The corresponding eigenvalues can be real (
p
2 > 0) or imaginary (
p
2 < 0). The method is developed both for massless and massive fermions for which it turns out to be particularly fast. All relevant formulae are given.
High-dose chemotherapy produces high complete remission (CR) rates and some survival advantage in patients with metastatic breast cancer (BC). A current issue is the possibility that these patients ...may have an even better prognosis with multiple high-dose treatments. In this study, we evaluated the feasibility of a four-step, high-dose sequential chemotherapy (HDSC) with double autologous hematopoietic progenitor-cell rescue. We also tested the hypothesis that peripheral-blood progenitor cells (PBPCs) harvested following a single recruitment with cyclophosphamide (CY) and granulocyte-macrophage colony-stimulating factor (GM-CSF) allow the safe administration of the whole HDSC with closely timed repeated courses of several non-cross-resistant agents.
The treatment plan included CY 7 g/m2, followed by GM-CSF 5 to 7 micrograms/kg/d administered by continuous intravenous (i.v.) infusion on days 2 to 14; PBPCs with or without bone marrow (BM) harvest; mitoxantrone (NOV) 60, 75, or 90 mg/m2 plus melphalan (L-PAM) 140 to 180 mg/m2 with hematopoietic rescue; methotrexate (MTX) 8 g/m2 plus vincristine (VCR) 1.4 mg/m2; and etoposide (VP-16) 1.5 g/m2 plus carboplatin (PP) 1.5 g/m2 with hematopoietic rescue.
All 15 patients enrolled completed the entire treatment and there were no toxic deaths. Hematologic reconstitution was good at each step. The median number of days with an absolute neutrophil count (ANC) less than 100/microL and platelet count less than 20,000/microL were 8 and 3, respectively, after NOV plus L-PAM, and 7 and 4, respectively, after VP-16 plus PP. The main non-hematologic toxicity was mucositis, while organ toxicity was mild and reversible.
This regimen is feasible, with acceptable toxicity. GM-CSF and PBPCs have a pivotal role, as they hasten hematologic reconstitution, abate toxicity, and allow rapid recycling.
Molecular signatures of tumors with prognostic and predictive value are now available. However, several technical problems prevent the performing of gene expression profiles in routine diagnostics. ...The highly sensitive fluorescence-based real-time quantitative reverse transcriptase-polymerase chain reaction procedure is able to analyze mRNA levels from formalin-fixed paraffin-embedded (FFPE) tissues, the most commonly available source of tumor samples with well-documented information. However, the time-dependent fragmentation and small amount of RNA extracted from FFPE requires a preliminary mRNA amplification step to amplify small amounts of mRNA without significantly distorting relative mRNA levels. The purpose of this study was to determine the performance of a commercial cDNA preamplification kit (TaqMan PreAmp Master Mix Kit) on RNA samples obtained from FFPE tissues, prepared, and archived for routine diagnosis. We tested the reliability and reproducibility of this procedure for performing low-density gene expression assay from FFPE tissue samples. The whole procedure reported herein is a powerful and reproducible approach for routine clinical purposes that can be performed even using poorer RNA quality samples and that allows the analysis of gene expression for 96 genes in stored samples.
To evaluate the safety and efficacy of pegfilgrastim administered as haematological support after autologous peripheral blood stem cell transplantation, we compared 44 patients with solid tumours and ...lymphomas receiving a 6-mg single dose of pegfilgrastim on day +5 after transplantation to a historical control group of 25 patients receiving filgrastim 5 μg kg
−1
day
−1
starting on day +5. There were no significant differences in haematological recovery nor in the incidence and duration of neutropenic fever. Median duration of grade 4 neutropenia in the pegfilgrastim and filgrastim group was similar. The incidence of grade III–IV mucositis was lower in pegfilgrastim than in filgrastim group due to the significant difference observed among the patients with solid tumours (
p
= 0.00). The only adverse event considered to be cytokine related was mild to moderate bone pain occurring during haematological recovery. According to the present study design and taking into account the current prices in our institution, the cost of the two drugs was similar in both treatment groups. In conclusion, a single injection of pegfilgrastim administered at day +5 post-transplantation shows comparable safety and efficacy profiles to daily injections of filgrastim and may be cost effective.
Acral erythema (AE) and eccrine squamous syringometaplasia (ESS) are distinctive clinico-pathological entities described in patients receiving chemotherapy for malignancies, mainly myelogenous ...leukemia. In no case of chemotherapy-induced AE have histopathologic changes of ESS been described. We report a patient with acute myelogenous leukemia who had typical AE due to cytarabine with histopathologic ESS. The latter findings in a case of AE may be a useful diagnostic clue for distinguishing chemotherapy-induced AE from palmo-plantar erythema of graft-vs-host reaction.
The aim of this study was to compare both the effects on hematologic recovery and circulating progenitor cell mobilization and the toxicity of three cytokine regimens administered after high-dose ...non-myeloablative chemotherapy with cyclophosphamide 5 g/m(2), etoposide 1.5 g/m(2) and cisplatin 150 mg/m(2). Thirty-five consecutive patients were non-random sequentially allocated to one of three treatment groups: (1) granulocyte colony-stimulating factor alone (n = 15); (2) granulocyte-macrophage colony-stimulating factor alone (n = 10), and (3) sequential interleukin-3 and granulocyte-macrophage colony-stimulating factor (n = 10). Neutrophil recovery in group 1 was significantly hastened as compared to the two other groups (median 2 days, p < 0.005), while no significant differences were observed between groups 2 and 3. CD34+ cells peaked about 2 days earlier in group 1 compared to the other groups (p = 0.0001), whereas the median peak value of CD34+ cells was similar in the three groups. In all patients, the toxicity related to cytokine administration was low and easily manageable with nonsteroidal anti-inflammatory drugs.
Overexpression of antiapoptotic Bcl-2 family members has recently been related to resistance to chemo/radiotherapy in several human malignancies, particularly lymphomas. Hence, innovative approaches ...bypassing this resistance mechanism are required in the therapeutic approach. This study evaluated whether chemoresistance associated with Bcl-2 and Bcl-x(L) overexpression would be overcome by activating the death receptor pathway by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the Jurkat cell model
We made use of genetically modified Jurkat cells to evaluate the effect of Bcl-2 or Bcl-x(L) overexpression on the cytotoxic effect produced by the anticancer drugs doxorubicin, etoposide, and oxaliplatin and TRAIL. Caspase activation was detected by cleavage of caspase-8 and -3. The mitochondrial transmambrane potential was assessed by staining with DiOC(6) and flow cytometry. Caspase activity was blocked by the broad-spectrum caspase inhibitor zVAD-fmk.
Bcl-2 and Bcl-x(L) overexpression but not lack of caspase-8 protects the Jurkat cells from the anticancer drug-induced cytolysis. However, Bcl-2/Bcl-x(L) Jurkat cells retained some susceptibility to TRAIL-induced cytolysis. A highly synergistic cytotoxic effect of the combination of TRAIL with any of the antiblastic used in this study was detected in the chemoresistant cells. This effect was associated with mitochondrial disassemblage and dependent on caspase activation
The combination of TRAIL with conventional anticancer drugs may prove to be useful in the treatment of antiapoptotic Bcl-2 family proteins-expressing malignancies.
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