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  • 1
    In: Ecology, Wiley, Vol. 100, No. 7 ( 2019-07)
    Abstract: Xenarthrans—anteaters, sloths, and armadillos—have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records ( n  = 5,941), and Cyclopes sp. have the fewest ( n  = 240). The armadillo species with the most data is Dasypus novemcinctus ( n  = 11,588), and the fewest data are recorded for Calyptophractus retusus ( n  = 33). With regard to sloth species, Bradypus variegatus has the most records ( n  = 962), and Bradypus pygmaeus has the fewest ( n  = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data.
    Type of Medium: Online Resource
    ISSN: 0012-9658 , 1939-9170
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1797-8
    detail.hit.zdb_id: 2010140-5
    SSG: 12
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  • 2
    In: Nature Ecology & Evolution, Springer Science and Business Media LLC, Vol. 5, No. 6 ( 2021-04-01), p. 757-767
    Type of Medium: Online Resource
    ISSN: 2397-334X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2879715-2
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  • 3
    In: Blood, American Society of Hematology, Vol. 117, No. 14 ( 2011-04-07), p. 3759-3769
    Abstract: Fanconi anemia is characterized by congenital abnormalities, bone marrow failure, and cancer predisposition. To investigate the origin, functional role, and clinical impact of FANCA mutations, we determined a FANCA mutational spectrum with 130 pathogenic alleles. Some of these mutations were further characterized for their distribution in populations, mode of emergence, or functional consequences at cellular and clinical level. The world most frequent FANCA mutation is not the result of a mutational “hot-spot” but results from worldwide dissemination of an ancestral Indo-European mutation. We provide molecular evidence that total absence of FANCA in humans does not reduce embryonic viability, as the observed frequency of mutation carriers in the Gypsy population equals the expected by Hardy-Weinberg equilibrium. We also prove that long distance Alu-Alu recombination can cause Fanconi anemia by originating large interstitial deletions involving FANCA and 2 adjacent genes. Finally, we show that all missense mutations studied lead to an altered FANCA protein that is unable to relocate to the nucleus and activate the FA/BRCA pathway. This may explain the observed lack of correlation between type of FANCA mutation and cellular phenotype or clinical severity in terms of age of onset of hematologic disease or number of malformations.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4414-4414
    Abstract: Abstract 4414 Introduction Discovery of novel non cytotoxic drugs for cancer focuses on targets selectively expressed in malignant cells, only testing at the end if they are toxic to patients. We have developed a novel approach to discover these drugs starting at the end; we screen 2.000 approved drugs with proven safety, directly on freshly extracted (ex vivo) blood samples of patients with Chronic Lymphocytic Leukemia (CLL). These screens are enabled by a novel technology platform based on automated flow cytometry we call ExviTech for ex vivo technology. Patients and Methods All screening studies were performed directly on either peripheral blood or bone marrow samples from 44 patients diagnosed with various subtypes of B-cell malignancies, after informed consent. Patient samples were diluted and plated with each of the 2.000 drugs individually, retaining the erythrocyte population and serum proteins to enable clinically relevant concentrations. The experimental assay was setup the same or a day after sample extraction. Each sample was diluted to achieve a leukemic cell concentration of approximately 3,000 cells/μl; then 45μl of the suspension is added to each well of 96-well plates that contain the pharmacological agents (final concentration of 30μM). The compound plates were then sequentially incubated for 24 hours at 37°C with 5% CO2 for screening (sterile conditions). After incubation, the erythrocytes were lysed and the leucocytes incubated with Annexin V-FITC, anti-CD45-APC and anti-CD19-PE added to each well. The plates were then transferred to an automated flow cytometry system where the contents of each well were aspirated and analyzed by a CyAn flow cytometer. Candidates from the primary screens were validated in additional samples with dose-responses, combinations with approved drugs, multiple incubation times, etc… Results Analyzing primary screens from 24 CLL patients, three related compounds (Vivia007, Vivia008 and Vivia009) were found to consistently induce apoptosis of nearly all leukemic B-cells from most of the patient samples diagnosed with B-cell chronic lymphocytic leukemia at levels equal to or greater than known CLL active cytotoxic agents. Notably, these candidates are equally effective against samples of p53 mutated patients. These 3 drugs are pharmacologically me-too drugs sharing the same target and mechanism of action, and are non cytotoxic drugs with a known and good safety profile, administered to millions of patients over many years. Validation experiments were done on 20 additional CLL patients and Vivia009 emerged as the most effective agent with an average EC50 of 18.2μM. The mechanism of action is different than the known mechanism of Vivia009 and its class members for their approved indications. Consistent with this observation, only 3 of 15 members of the same pharmacological drug class were efficacious against CLL malignant cells. All 3 Vivia′s candidates were equally efficacious against other B-Cell Malignancies such as B-ALL (pediatric and adult), and Multiple Myeloma. These drugs are not effective in their current oral formulation and require a novel intravenous formulation. Interestingly, kinetics of induction of apoptosis were faster for Vivia009 than for fludarabine, cyclophosphamide and mitoxantrone. Vivia009 requires only 1 hour of incubation with fresh cells to induce maximal apoptosis. This timeline is less than the 3 hours in which Vivia009 was found present at high concentrations in bone marrow of rats using a single intravenous bolus. Thus, Vivia009 seems to fulfill the pharmacokinetic criteria to eliminate all leukemic cells with a single intravenous bolus, which would be a major advantage over current treatments (5-days fludarabine or 3 days FCR). Animal models are ongoing to confirm the non cytotoxic nature of the candidates in the novel IV formulation and the fewer days needed to reach remission, both compared with fludarabine monotherapy. Conclusions In summary, our results demonstrate the potential of the ExviTech technology platform as a successful model for the systematic search of new uses for already existing approved drugs directly on patient samples of hematological malignancies. A new drug candidate with excellent safety profile has been identified with similar efficacy ex vivo as the best approved cytotoxic drugs, which is a non-cytotoxic drug with fast kinetics that might enable significantly safer and shorter treatments. Disclosures: Bennett: Vivia Biotech: Employment. Sapia:Vivia Biotech SL: Employment. Primo:Vivia Biotech SL: Employment. Suarez:Vivia Biotech SL: Employment. Lago:Vivia Biotech SL: Employment. Matoses:Vivia Biotech: Employment. Espinosa:Vivia Biotech: Ana Espinosa, Employment. Tudela:Vivia Biotech SL: Employment. Arroyo:Vivia Biotech SL: Employment. Jackson:Vivia Biotech SL: Employment. Okun:Vivia Biotech SL: Research Funding. Lopez:Vivia Biotech SL: Employment. Gornemann:Vivia Biotech SL: Employment. Diez:Vivia Biotech SL: Employment. González:Vivia Biotech SL: Consultancy. Dominguez-Gil:Vivia Biotech SL: Consultancy. Troconiz:Vivia Biotech SL: Consultancy. Rodriguez de Fonseca:Vivia Biotech SL: Consultancy. Saunders:Vivia Biotech: Consultancy. Montejo:Vivia Biotech SL: Consultancy. Caveda:Vivia Biotech SL: Employment. Orfao:Vivia Biotech SL: Research Funding. Ballesteros:Vivia Biotech SL: Equity Ownership.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: American Journal of Hematology, Wiley, Vol. 88, No. 5 ( 2013-05), p. 359-364
    Type of Medium: Online Resource
    ISSN: 0361-8609
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 1492749-4
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  • 6
    In: Medical and Pediatric Oncology, Wiley, Vol. 26, No. 4 ( 1996-04), p. 268-271
    Type of Medium: Online Resource
    ISSN: 0098-1532 , 1096-911X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 1996
    detail.hit.zdb_id: 2001838-1
    detail.hit.zdb_id: 2130978-4
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  • 7
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2655-2655
    Abstract: Abstract 2655 Poster Board II-631 Introduction: The predictive power of measuring the effect of anticancer treatments on whole living tumor cells freshly removed from cancer patients, called Individualized Tumor Response Testing (ITRT), has been recently further validated in a clinical trial, the UK's LRF CLL4 trial (Bosanquet ASH 2007). It predicts resistance better than sensitivity. We present a novel approach to ITRT based on measuring drug induced apoptosis of tumor cells in whole blood ex vivo (in vitro using freshly extracted samples). It uses a novel automated flow cytometry platform (ExviTech) capable of evaluating hundreds of drugs and drug combinations used in current treatment protocols, and can address the significant scaling of potential future protocols induced by a number of new drug approvals in each indication. Patients and Methods: We evaluated 47 samples of peripheral blood or bone marrow from patients diagnosed with hematological malignancies: 20 chronic Lymphocytic Leukemia (CLL), 14 Acute Lymphoblastic Leukemia (ALL), 7 Multiple Myeloma (MM), and 6 Acute Myeloblastic Leukemia (AML). After informed consent, samples, collected into heparin, were processed the same or the next day. Whole blood was diluted and incubated with drugs for 24 and 48 hours. Whole blood was used to retain erythrocytes and serum proteins enabling more clinically relevant physiological conditions. Three types of drugs were tested: 1) Approved drugs for each indication, including all possible pair wise combinations, and combinations administered within current and experimental protocols as advised by the PETHEMA groups in Spain. 2) Concomitant medicines (Con-Meds), including alternative drugs within the same class of antacids, antiemetics, etc… to test whether they may also induce apoptosis 3) Drugs in clinical trials, preferentially Phase III drugs, alone and in combination with approved drugs, which may form the basis of future treatment protocols. Drugs were plated at a final concentration equivalent to their reported plasma Cmax concentration. Synergistic drug combinations were identified as one drug potentiating the effect of the other. Results: The efficacy of each drug and combination tested was categorized as highly resistant, intermediate or highly sensitive. Highly resistant drug results were contraindicated. Among the highly sensitive treatments ex vivo, often those that effectively killed all malignant cells, we selected those whose drugs were significantly less toxic as treatment guidelines, highlighting those treatment protocols that act faster ex vivo (24 vs 48 hours) and/or show synergistic combinations. The final result was a set of multiple reasonable ex vivo options for hematologists. The efficacy of individual drugs varied notably from patient to patient, , as reported earlier by other methods. Drug-drug combinations show surprising results. Some combinations, effective at high doses, kill 80% of malignant cells when combined in low concentrations at which the individual drugs kill only 10%20% of these cells. On the contrary, many drug combinations were antagonistic, effectively turning them into cytoprotectors and the patient into potential resistance. Specific combinations that show consistent efficacy across samples are indicative of potential new protocols. Surprisingly, for a proportion of patients, some of the Con-Meds were highly efficient in killing malignant cells selectively. For example, in a particular CLL patient an antacid and an antiviral drug had similar efficacies as the best approved cytotoxic drugs. In other patients, drugs still in clinical trials showed high sensitivity and highly selective apoptosis – suggesting that those patients could be referred for inclusion into these trials, which could represent new alternatives especially for refractory patients with few therapeutic options available. Conclusions: We have developed a Personalized Medicine Multi-Drug ex vivo test, evaluating the efficacy of hundreds of drugs and drug combinations in whole blood. This scale could address the predictable expansion of multi-drug potential treatments as the existing extensive drug pipeline delivers new drug approvals, exploring hundreds of new protocols ex vivo. Promising results obtained ex vivo (in vitro using freshly extracted samples) need to be verified in clinical trials. Disclosures: Bennett: Vivia Biotech: Employment. Sapia:Vivia Biotech SL: Employment. Primo:Vivia Biotech SL: Employment. Suarez:Vivia Biotech SL: Employment. Lago:Vivia Biotech SL: Employment. Matoses:Vivia Biotech SL: Employment. Espinosa:Vivia Biotech SL: Employment. Tudela:Vivia Biotech SL: Employment. Arroyo:Vivia Biotech SL: Employment. Gorrochategui:Vivia Biotech SL: Employment. Jackson:Vivia Biotech SL: Employment. Okun:Vivia Biotech SL: Research Funding. Lopez:Vivia Biotech SL: Employment. Gornemann:Vivia Biotech SL: Employment. Diez:Vivia Biotech SL: Employment. Gonzáalez:Vivia Biotech SL: Consultancy. Bosanquet:Vivia Biotech SL: Consultancy. Orfao:Vivia Biotech SL: Research Funding. Ballesteros:Vivia Biotech SL: Equity Ownership.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1627-1627
    Abstract: Abstract 1627 Poster Board I-653 Background Leukemic blasts from B-cell acute lymphoblastic leukemia (B-ALL) and T-ALL circulate through the blood stream and may infiltrate different organs. Extramedullary organs may act as sanctuaries for lymphoblasts, preventing the exposure to adequate levels of chemotherapeutic drugs. Typical extramedullary relapses are seen in testes and in central nervous system (CNS). We aimed at determining whether chemokines may play a role in the infiltration of the CNS by leukemic blasts in childhood ALL. We studied the expression of chemokine receptors in ALL blasts in marrow, as well as the levels of chemokine ligands in the cerebrospinal fluid (CSF) of children with B- or T-ALL. If chemokines had a role in CNS leukemic infiltration, the following should be confirmed: leukemic blasts should express high levels of the chemokine receptor/s for which high levels of its corresponding ligand/s were detected at the CNS. Methods This prospective study was approved by the local ethical committees for clinical research. Samples from 80 children in 10 Spanish pediatric oncology units were obtained. We detected the presence of leukemic blasts in CFS by flow cytometry. We defined leukemic infiltration of CFS samples as the presence of cells with the same immunophenotype as the leukemia in the marrow aspirates. We detected the expression levels of 9 CCR and 6 CXCR molecules in ALL blasts by flow cytometry in marrow aspirates. Levels of chemokine ligands were quantitated by Cytometric Bead Array or by commercial ELISA kits in CSF samples. Results We found that chemokine receptors expression and levels of chemokine ligands varied depending upon the lineage (T versus B), the maturation state (pre-T versus T; pro-B versus pre-B versus common-B) and the risk-status (high versus non-high) of the leukemia. T-ALL patients with high levels of CNS leukemic infiltration expressed significantly higher levels of CXCL10 compared to the same parameters of T-ALL patients with low/absent levels of CNS disease (p=0,049). Common B-ALL patients with high levels of CNS leukemic infiltration expressed higher levels of CCL22 compared to that of common B-ALL patients with low/absent levels of CNS disease (p=0,059). Among the 4 patients with a CNS relapse, we detected higher levels of CXCR3 (p=0,0038) and of its ligand, CXCL10 (p=0,0169), compared to patients who did not relapse. Conclusions Our study suggests that the CXCR3/CXCL10 axis may be involved in the CNS relapse of high-risk ALL in children: high expression of CXCR3 on marrow blasts plus high levels of CXCL10 in the CNS was associated with leukemic CNS relapse. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 23, No. 12 ( 2005-04-20), p. 2618-2628
    Abstract: To improve outcome for children with nonmetastatic rhabdomyosarcoma and to reduce systematic use of local therapy. Patients and Methods Five hundred three previously untreated patients aged from birth to 18 years, recruited between 1989 and 1995, were allocated to one of six treatment schedules by site and stage. Results Five-year overall survival (OS) and event-free survival (EFS) were 71% and 57%, respectively. Primary site, T-stage, and pathologic subtype were independent factors in predicting OS by multivariate analysis. Differences between EFS and OS reflected local treatment strategy and successful re-treatment for some patients after relapse. Patients with genitourinary nonbladder prostate tumors had the most favorable outcome (5-year OS, 94%): the majority were boys with paratesticular tumors treated successfully without alkylating agents. Patients with stage III disease treated with a novel six-drug combination showed improved survival compared with the Malignant Mesenchymal Tumor 84 study (MMT 84; 5-year OS, 60% v 42%, respectively). OS was not significantly better than that achieved in the previous MMT 84 study, but 49% of survivors were cured without significant local therapy. Conclusion Selective avoidance of local therapy is justified in some patients, though further work is required to prospectively identify those for whom this is most applicable. Exclusion of alkylating agents is justified for the most favorable subset of patients. The value of the new six-drug chemotherapy combination is being evaluated further in a randomized study (MMT 95).
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2005
    detail.hit.zdb_id: 2005181-5
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  • 10
    In: Scandinavian Journal of Psychology, Wiley, Vol. 56, No. 3 ( 2015-06), p. 306-314
    Abstract: Surviving childhood cancer has multiple implications on both physical and psychological domains of the individual. However, its study and possible effects on health‐related quality of life ( HRQ oL) outcomes of adolescent survivors has been understudied. The objective of this study was twofold; to assess positive and negative cancer‐related consequences (psychosocial and physical) in a sample of adolescent cancer survivors and to explore their relationship with HRQ oL outcomes. Forty‐one participants answered two questions about positive and negative consequences in the aftermath of cancer and filled in the KIDSCREEN ‐52 self‐reported version. Data were analysed using mixed methods approach. Overall, 87.8% of the studied sample identified positive consequences and 63.4% negative consequences in survivorship. Four positive categories and five negative categories with regard to cancer‐related consequences were found. Changed perspectives in life narratives seem to be the positive consequence more related to HRQ oL (physical well‐being, mood & emotions, autonomy, social support & peers), followed by useful life experience (physical well‐being, autonomy, social support & peers). Psychological impact was the most referred negative consequence with a significant detrimental effect on social support and peers HRQ oL dimension. Even if the majority of survivors reported benefit finding in the aftermath of cancer, concomitant positive and negative consequences have been found. However, findings only reveal a significant relationship between positive narratives and HRQ oL, and negative consequences do not seem to have a significant influence on overall HRQ oL in survivorship.
    Type of Medium: Online Resource
    ISSN: 0036-5564 , 1467-9450
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2022171-X
    SSG: 5,2
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