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Purpose: Secretory breast cancer (SBC) is one of the rarest breast cancer (BC), representing the majority of BC in childhood. Nevertheless, it elicits a lot of interest both for the peculiar morphology and the characteristic genetic features. Currently, there is no consensus on optimal treatment strategy. Therefore, it is useful to report every case in order to establish treatment algorithms.Methods: We describe the case of a 6-year-old boy diagnosed with a SBC, with peculiar genomic and immunohistochemical features. Moreover, we carried out a review of the literature in order to analyze the present state of knowledge about this rare entity.Results: To the best of our knowledge, there are only 120 cases published in literature, only 32 in males and only 2 younger than 6 years. Furthermore, this one had peculiar genomic and immunohistochemical features. Indeed, even if SBC expresses basal-cell markers, our patient had a triple-negative tumor expressing both basal and luminal cell markers. Furthermore, the boy’s genomic profile revealed not only positivity for the typical SBC’s translocation t(12;15), but also for a 3q28 duplication, found in his father (healthy) and paternal grandfather (with a previous BC). None were positive for BRCA mutation. This locus includes only one gene encoding for a growth factor recently linked to Early Infantile Epileptic Encephalopathy-47 and Idiopathic ventricular tachycardia. Even if the literature does not provide evidence of a pathogenic role it is not possible to exclude a cancer-predisposing activity.Conclusions: SBC is a rare type of BC, characterized by triple-negative features with an unexpectedly good prognosis. More data are needed to fully understand the behavior of this cancer and genomic profiling could be helpful in improving its diagnosis and management. [ABSTRACT FROM AUTHOR]

We prove that Misiurewicz parameters with prescribed combinatorics and hyperbolic parameters with ( d − 1) distinct attracting cycles with given multipliers are equidistributed with respect to the bifurcation measure in the moduli space of degree d complex polynomials. Our proof relies on Yuan's equidistribution results of points of small heights, and uses in a crucial way Epstein's transversality results. [ABSTRACT FROM AUTHOR]

We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining BU, Cyclophosphamide and Melphalan; AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML. [ABSTRACT FROM AUTHOR]

The insulin-like growth factor (IGF-I) signalling pathway is essential for metabolism, cell growth and survival. It induces expression of the mitochondrial pyrimidine nucleotide carrier 1 (PNC1) in transformed cells, but the consequences of this for cell phenotype are unknown. Here we show that PNC1 is necessary to maintain mitochondrial function by controlling mitochondrial DNA replication and the ratio of transcription of mitochondrial genes relative to nuclear genes. PNC1 suppression causes reduced oxidative phosphorylation and leakage of reactive oxygen species (ROS), which activates the AMPK-PGC1α signalling pathway and promotes mitochondrial biogenesis. Overexpression of PNC1 suppresses mitochondrial biogenesis. Suppression of PNC1 causes a profound ROS-dependent epithelial–mesenchymal transition (EMT), whereas overexpression of PNC1 suppresses both basal EMT and induction of EMT by TGF-β. Overall, our findings indicate that PNC1 is essential for mitochondria maintenance and suggest that its induction by IGF-I facilitates cell growth whereas protecting cells from an ROS-promoted differentiation programme that arises from mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Summary:The purpose of this multicenter study was to assess the incidence and the treatment of hemorrhagic cystitis (HC) in 1218 pediatric patients, with a mean age of 10.8 years, who underwent hematopoietic stem cell transplantation (HSCT). In all, 44 patients (3.6%) developed HC a median 23 days after HSCT. The incidence of HC was higher in allogeneic than in autologous HSCT recipients (P=0.0001). Of the 44 patients, 37 (84%) recovered from HC in a median 30 days (range 3-100); the other seven children died while still suffering from HC. Hyperbaric oxygen therapy (HOT) achieved significantly better results than prostaglandin therapy (P=0.02) in the treatment of grade II-III HC. By multivariate analysis, age <96 months and allogeneic HSCT were significantly associated with the occurrence of HC: P=0.008 and 0.013, respectively. After a median follow-up of 5.75 years, the 5-year survival of patients who did or did not develop HC was: 43 vs 52%, P=0.03, respectively. This study indicates that age and type of HSCT are factors predisposing to HC in children given HSCT and demonstrates the promising role of HOT in a conservative approach to HC treatment.Bone Marrow Transplantation (2003) 32, 925-931. doi:10.1038/sj.bmt.1704252 [ABSTRACT FROM AUTHOR]

Summary:We analyzed the outcome of 167 consecutive children with second CR acute lymphoblastic leukemia (ALL), for whom an unrelated donor (UD) search was activated between 1989 and 1998 at a median time of 2 months after relapse. A suitable donor was identified for 70 patients at 1 year and 6.5 months before and after 1995 from search activation, respectively; a further leukemia relapse occurred during the search in 94 children at a median of 4 months after search activation, 36 of whom underwent UD (14) or other types of transplant (22), beyond second CR, while 58 died of progressive disease. Of 73 patients not experiencing a second relapse, 64 underwent UD (46) or other types of transplant (18), while nine proceeded with chemotherapy, and only four of them survived. The 3-year disease-free survival (DFS) from second CR for the 167 patients is 15.1%, whereas 3-year DFS after transplant for the 60 UD and 40 alternative donor transplanted children is 31.6 and 25.4%, respectively. In conclusion, a further relapse is the main factor adversely affecting outcome of children with second CR ALL. Thus, for these patients, the search should be activated early after relapse and either a UD or an alternative transplant should be performed as early as possible.Bone Marrow Transplantation (2003) 32, 325-331. doi:10.1038/sj.bmt.1704132 [ABSTRACT FROM AUTHOR]

Preliminary randomized studies have failed to show a survival benefit of high-dose chemotherapy with alkylators in advanced breast cancer. Idarubicin is an active agent in breast cancer and is suitable for dose escalation. We designed a dose finding study with escalating high-dose idarubicin (HD-Ida) followed by fixed high-dose thiotepa+melphalan (HD-TM) with peripheral blood progenitor cells (PBPC) in MBC patients with stable disease or in partial response after six courses of induction chemotherapy with gemcitabine 1000?mg/m2 days 1 and 4, epirubicin 90?mg/m2 day 1, taxol 175?mg/m2 day 1 (GET). Aims of the study were to identify the maximum tolerated dose (MTD) of idarubicin, to evaluate the cardiac safety and activity of HD-Ida and HD-TM after GET and to study the pharmacokinetic profile of idarubicin and idarubicinol. A total of 14 patients were treated. Idarubicin was administered as a 48?h continuous i.v. infusion at the following dose levels: 40?mg/m2 (three patients), 50?mg/m2 (three patients), 60?mg/m2 (five patients) and 70?mg/m2 (three patients). Mucositis was the dose-limiting toxicity and the MTD was 60?mg/m2. Cmax of Idarubicin and idarubicinol were 7.7±2.0 and 26.3±9.7?ng/ml at 40?mg/m2 and increased to 14.8+3.0 and 47.4+12.6?ng/ml at 70?mg/m2. AUCt0-264 of idarubicin and idarubicinol increased from 423.2±111.6 and 2581±606?hng/ml at 40?mg/m2 to 732.8±140.2 and 4590±1258?hng/ml at 70?mg/m2. Conversion rates after HD-Ida and HD-TM were 28.6 and 38.5%, respectively. No episodes of cardiac toxicity were observed. We conclude that HD-Ida followed by HD-TM is feasible and devoid of cardiac toxicity. Moreover, the activity of HD-Ida after a epirubicin-containing regimen suggests incomplete crossresistance between the two drugs.Bone Marrow Transplantation... [ABSTRACT FROM AUTHOR]

Dok proteins are adapter proteins involved in signal transduction. Several intracellular proteins expressed in lymphocytes meet the criteria of membrane-associated adapter proteins such as members of the Dok family. To understand the role and the formation of multiprotein networks involving Dok proteins in T lymphocytes, we search for potential additional members of this family. Here, we describe the two new human dok-related genes DOK4 and DOK5 and present data showing the expression of DOK4 and DOK5 genes in T cells. These genes are the orthologues of mouse Dok4 and Dok5 genes. Based on analysis of phylogenetic trees and exon/intron structure of Dok family members, DOK4 and DOK5 define a subfamily within dok genes distinct from DOK1, DOK2 and DOK3. So, Dok-4 and Dok-5 molecules constitute a new group of adapter proteins in T cells, requiring further functional analysis. [ABSTRACT FROM AUTHOR]

Attempts to verify whether reduction in transplant-related mortality (TRM) of children with acute lymphoblastic leukemia in second complete remission given allogeneic hematopoietic stem cell transplantation from unrelated volunteers has occurred over time. Role of other variables on the probabilities of relapse, TRM and event-free survival; Engraftment and chronic graft-versus-host disease occurrence.

We have investigated, both theoretically and experimentally, multiphoton-induced processes in aerosol particles using femtosecond laser pulses. More specifically, we have demonstrated that both multiphoton (1, 2 and 3 photon)-induced fluorescence (MPEF) and laser-induced breakdown (LIB) emissions are strongly enhanced in the backward direction. The backward enhancement increases from 1.8 to 35 (emission ratio between the backward direction and 90°) with increasing non-linear process order n. Application to non-linear lidar of biological aerosols is discussed. [ABSTRACT FROM AUTHOR]

Clinical and experimental pharmacokinetic interaction between 6-mercaptopurine (6-MP) and methotrexate (MTX) was investigated in patients as well as in rats and in HL-60 human leukemic cells. Ten children affected by acute lymphoblastic leukemia (ALL) in remission received daily doses of 6-MP given at 25 mg/m2 and i.v. infusion of high-dose MTX at 2 or 5 g/m2 once every other week. When 6-MP was given alone, the mean peak plasma concentration (Cmax) and area under the curve (AUC) of 6-MP were 72.5 ng/ml and 225.3 h ng ml(-1). Concurrent treatment with MTX at 2 or 5 g/m2 resulted in a mean increase of 108% and 121% in the Cmax and of 69% and 93% in the AUC, respectively. In rats treated with an oral dose of 6-MP at 75 mg/m2, MTX given i.p. at 5 g/m2 produced mean increases of 110% and 230% in the Cmax and AUC of 6-MP, respectively. In HL-60 human leukemic cells incubated with 6-MP at 250 ng/ml, the cumulative intracellular concentration of 6-thioguanine and 6-MP nucleotides was not significantly modified by treatment with 20 micrograms/ml of MTX. The present findings indicate that high-dose MTX enhances the bioavailability of 6-MP as evidenced by the observed increases in the plasma Cmax and AUC of 6-MP in humans and animals. [ABSTRACT FROM AUTHOR]

From January 1984 to December 1994, ABMT was performed on 154 children (101 males, 53 females; median age 10, range 3-21 years) with ALL and registered for BMT by the AIEOP (Italian Association of Paediatric Haemato-Oncology). All patients were in CR: 98 were in 2nd CR and 56 were in >2nd CR. Fifteen children (9.7%) died of transplant-related mortality. Ninety-five patients (61.6%) relapsed at a median of 5 (range 1-42) months after ABMT. The 8-year EFS according to preBMT status was 34.6% (s.e. 4.9) for 2nd CR patients and 10.6% (s.e. 5.6) for patients in >2nd CR. By univariate analysis, site of relapse (isolated extramedullary (IE) vs BM: EFS = 68.5% vs 18.2%; P < 0.0001) and TBI containing regimen (TBI vs no TBI: EFS = 48.1 vs 15.4%; P = 0.0023) were significant factors for 2nd CR patients. When the 2nd CR subset with BM involvement was analysed, TBI became insignificant (EFS = 25.4 vs 11.8%). No factors influenced EFS in patients in >2nd CR. By multivariate analysis, site of relapse was the only significant factor in 2nd CR patients (P < 0.0001). In conclusion, ABMT is an effective treatment after one early IE relapse. Few patients can be rescued after BM relapse. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox’s regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9)) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P < 0.01). in the allo group four out of nine patients were in ccr 4–5 years post-transplant. this study suggests that abmt may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd cr after an early isolated cns relapse. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about acute myeloid leukemia published in the 2004 issue of "Leukemia."

We describe the case of a HBsAg +, HBeAg + carrier, treated with lamivudine, who experienced exacerbation of hepatitis after BMT from an anti-HBs +, anti-HBc +, anti-HBe + donor. The serological profile of the donor and the timing of exacerbation suggested that the adoptive immunity transfer played a major pathogenetic role. Antilymphocyte globulin administration resulted in resolution of hepatitis and seroconversion to anti-HBs +. Therapy aimed at blocking the effector arm of liver damage could represent a novel approach to avoid the risk of progression to fulminant hepatitis without hampering the chances of recovery from hepatitis B. [ABSTRACT FROM AUTHOR]

We report a 21-year-old man who experienced symptoms of colitis following autologous TBI-conditioned PBSC transplantation, which persisted despite conventional treatment. Abdominal echography showed a thickened, stratified wall of the cecum, of the right colon and of part of the transverse colon. Hyperbaric oxygen therapy (20 sessions of 100% oxygen inhalation at 2.5 bar for 120 min in a hyperbaric chamber) achieved a prompt clinical recovery as well as complete disappearance of the ultrasound abnormalities. [ABSTRACT FROM AUTHOR]