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  • 1
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    DDRE-19. SPIDER VENOMS AS SOURCES OF MOLECULES FOR NEW CANCER TREATMENTS: THE EFFECTS OF THE SNX-482 PEPTIDE ON MACROPHAGE MODULATION
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii65-ii65
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii65-ii65
    Abstract: Malignant primary brain tumors remain among the most difficult cancers to treat. In malignant tissues, macrophages are accumulated in a high infiltration being known as tumor-associated macrophages (TAMs). These cells are associated with poor prognostics in many types of cancer. Studies in our group demonstrated that the venom of Phoneutria nigriventer (PnV), a wandering spider from South America, has reduced the development of glioblastoma (GBM) in a murine model, inducing a large infiltrate of TAMs. Subsequently, in vitro results demonstrated that PnV activates macrophages, increasing the ability to kill tumor cells. The aim of this study was to analyze the effects of the peptide SNX-482 presented in the venom of Hysterocrates gigas in macrophages for further correlation with the PnV. Macrophages were differentiated from bone marrow precursors collected from male C57BL6 mice and differentiated for 7 days with M-CSF. These cells were used for polarization and coculture with T cells and analyzed by flow cytometry. PCR Array was also performed (QIAGEN) for the analysis of gene expression. The results showed that SNX-482 could activate macrophages in a not dose-dependent response. There was an increase in the main activation markers (CD40, CD80, CD86, CD68, CD83, and MHCII). The polarization indicated that the peptide potentiated the proinflammatory effect of M1 macrophages (increased MHCII and iNOS). The screening of 86 cancer-related genes showed that the Ccr4, Pdcd1, Gzmb, and IFN-γ genes had an increase in their expression. Furthermore, we developed in C57BL/6 mouse a pre-clinical model of intracranial glioblastoma using the Gl261 cell line. The results showed an applied-easy-safe model that could alter the gene expression of cancer markers. Taken together, all the results contributed to increasing the knowledge about the peptide SNX-482 and the model for further pre-clinical assays of glioblastoma, making a great advance in the development of new treatments.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.264
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 2
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    Components from spider venom activate macrophages against glioblastoma cells: new potential adjuvants for anticancer immunotherapy
    Oxford University Press (OUP) ; 2021
    In:  The Journal of Biochemistry Vol. 170, No. 1 ( 2021-09-22), p. 51-68
    Details
    In: The Journal of Biochemistry, Oxford University Press (OUP), Vol. 170, No. 1 ( 2021-09-22), p. 51-68
    Abstract: Immunomodulation has been considered an important approach in the treatment of malignant tumours. However, the modulation of innate immune cells remains an underexplored tool. Studies from our group demonstrated that the Phoneutria nigriventer spider venom (PnV) administration increased the infiltration of macrophage in glioblastoma, in addition to decreasing the tumour size in a preclinical model. The hypothesis that PnV would be modulating the innate immune system led us to the main objective of the present study: to elucidate the effects of PnV and its purified fractions on cultured macrophages. Results showed that PnV and the three fractions activated macrophages differentiated from bone marrow precursors. Further purification generated 23 subfractions named low weight (LW-1 to LW-12) and high weight (HW-1 to HW-11). LW-9 presented the best immunomodulatory effect. Treated cells were more phagocytic, migrated more, showed an activated morphological profile and induced an increased cytotoxic effect of macrophages on tumour cells. However, while M1-controls (LPS) increased IL-10, TNF-alpha and IL-6 release, PnV, fractions and subfractions did not alter any cytokine, with the exception of LW-9 that stimulated IL-10 production. These findings suggest that molecules present in LW-9 have the potential to be used as immunoadjuvants in the treatment of cancer.
    Type of Medium: Online Resource
    ISSN: 0021-924X , 1756-2651
    URL: Article
    DOI: 10.1093/jb/mvab020
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2009977-0
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  • 3
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    EXTH-28. MOLECULAR CHARACTERIZATION OF HUMAN GLIOMAS AND IDENTIFICATION OF NEOPLASMS RESPONSIBLE FOR NEW BIOPHARMACEUTICALS OBTAINED FROM ANIMAL VENOM: A TRANSLATIONAL APPROACH
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii92-ii93
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii92-ii93
    Abstract: Gliomas correspond to approximately 80% of primary malignant brain tumors in adults. Associate histopathological classification to the identification of the molecular profile of these tumors is a great strategy to predict the tumor’s behavior and its responsiveness to the treatments. Studies have shown the potential of using biopharmaceuticals against cancer. Our research group has recently found two main subfractions isolated from Phoneutria nigriventer spider venom (PnV) (called SF1 and SF11) that can act decreasing the number of migrating cells during transwell assay. Therefore, the present study aimed to characterize, as regards molecular identity, the responsiveness of glioma samples collected from patients to the molecules purified from the PnV, in order to improve diagnostic and prognostic predictions, as well as contribute to the development of new drugs. After consent of the patients, samples of the tumors clinically diagnosed as glioma were collected during the surgical procedure to cultivation, that were performed until 10 passages to establish a lineage before use. To analyze its responsiveness to PnV in a migration assay, cultured human glioblastoma (1-JA63) cells were treated with PnV-isolated (HPLC) subfractions (SF1 and SF11 at 1 µg/ml) for 12 and 48 h (control stayed in IMDM) in a transwell system. SFs (mainly SF1) treatment induced a significant reduction in the number of migrating cells after 48 hours of exposure, in comparison to the control (untreated). Ongoing trials continue the establishment of another tumor samples of gliomas and migration tests with PnV subfractions will be carried out, to compare their effects in relation to other degrees of the disease also correlating the tumor response to the drug with the molecular profile. The results will contribute to the development of a potential individualized therapy also adding information about the correlation between the molecular identity of the tumor and its prognosis.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.382
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 4
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    EXTH-42. SPIDER VENOM COMPONENTS DECREASE GLIOBLASTOMA CELL MIGRATION AND INVASION THROUGH RHOA-ROCK AND NA+/K+-ATPASE β2: POTENTIAL MOLECULAR ENTITIES TO TREAT INVASIVE BRAIN CANCER
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii96-ii96
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii96-ii96
    Abstract: Glioblastoma (GB) cells have the ability to migrate and infiltrate the normal parenchyma, leading to the formation of recurrent tumors often adjacent to the surgical extraction site. We recently showed that Phoneutria nigriventer spider venom (PnV) has anticancer effects mainly on the migration of human GB cell lines (NG97 and U-251). The present work aimed to investigate the effects of isolated components from the venom on migration, invasiveness, morphology and adhesion of GB cells. The involvement of RhoA-ROCK signaling and Na+/K+-ATPase β2 (AMOG) was also evaluated. Human (NG97) GB cells were treated with twelve subfractions (SFs - obtained by HPLC from PnV). Migration and invasion were evaluated by scratch wound heling and transwell assays, respectively. Cell morphology and actin cytoskeleton were shown by GFAP and phalloidin labeling. The assay with fibronectin coated well plate was made to evaluate cell adhesion. Western blotting demonstrated ROCK and AMOG levels and a ROCK inhibitor was used to verify the involvement of this pathway. Two (SF1 and SF11) of twelve SFs decreased migration and invasion compared to untreated control cells. Both SFs also altered actin cytoskeleton, changed cell morphology and reduced adhesion. SF1 and SF11 increased ROCK expression and the inhibition of this protein abolished the effects of both subfractions on migration, morphology and adhesion (but not on invasion). SF11 also increased Na+/K+-ATPase β2. All components of the venom were evaluated and two SFs were able to impair human glioblastoma cells. The RhoA effector, ROCK, was shown to be involved in the mechanisms of both PnV components. It is possible that AMOG mediates the effect of SF11 on the invasion. Further investigations to isolate and biochemically characterize the molecules are underway. Support: FAPESP #2015/04194-0; CNPq #431465/2016–9.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.396
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 5
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    The Sexology Clinic at the Faculty of Psychology of the University of Lisbon
    Oxford University Press (OUP) ; 2017
    In:  The Journal of Sexual Medicine Vol. 14, No. Supplement_4b ( 2017-05-01), p. e227-e227
    Details
    In: The Journal of Sexual Medicine, Oxford University Press (OUP), Vol. 14, No. Supplement_4b ( 2017-05-01), p. e227-e227
    Type of Medium: Online Resource
    ISSN: 1743-6109 , 1743-6095
    URL: Article
    DOI: 10.1016/j.jsxm.2017.04.194
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
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  • 6
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    The Impact of COVID-19 on Sexual Health: A Preliminary Framework Based on a Qualitative Study With Clinical Sexologists
    Oxford University Press (OUP) ; 2021
    In:  Sexual Medicine Vol. 9, No. 1 ( 2021-02-01), p. 100299-100299
    Details
    In: Sexual Medicine, Oxford University Press (OUP), Vol. 9, No. 1 ( 2021-02-01), p. 100299-100299
    Abstract: In recent months, some attempts were made to understand the impact of COVID-19 on sexual health. Despite recent research that suggests COVID-19 and lockdown measures may eventually impact sexual response and sexually related behaviors, we are missing clinical sexologists’ perspectives on the impact of COVID-19 in sexual health. Such perspectives could inform a preliminary framework aimed at guiding future research and clinical approaches in the context of COVID-19. Aim To explore the perspectives of clinical sexologists about the impact of COVID-19 on their patients’ sexual health, as well as the professional challenges they have faced during the current pandemic. Findings are expected to inform a preliminary framework aimed at understanding the impact of COVID-19 on sexual health. Methods We conducted an online qualitative exploratory survey with 4 open-ended questions with 39 clinical sexologists aged between 32 and 73 years old. The survey was advertised among professional associations’ newsletters. We performed a Thematic Analysis using an inductive, semantic, and (critical) realist approach, leading to a final thematic map. Main Outcome Measures The outcome is the thematic map and the corresponding table that aggregates the main themes, subthemes, and codes derived from participants’ answers and that can serve as a preliminary framework to understand the impact of COVID-19 on sexual health. Results The final thematic map, expected to serve as a preliminary framework on the impact of COVID-19 in sexual health, revealed 3 main themes: Clinical Focus, Remapping Relationships, and Reframing Technology Use. These themes aggregate important interrelated issues, such as worsening of sexual problems and dysfunctions, mental health, relationship management, the rise of conservatism, and the use of new technology that influences sexuality and sexual health-related services. Conclusion The current study allowed us to develop a preliminary framework to understand the impact of COVID-19 on sexual health. This framework highlights the role of mental health, as well as the contextual nature of sexual problems, and subsequently, their relational nature. Also, it demonstrates that the current pandemic has brought into light the debate of e-Health delivery within clinical sexology.
    Type of Medium: Online Resource
    ISSN: 2050-1161
    URL: Article
    DOI: 10.1016/j.esxm.2020.100299
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2734882-9
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  • 7
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    Kinetics of sugars consumption and ethanol inhibition in carob pulp fermentation by Saccharomyces cerevisiae in batch and fed-batch cultures
    Oxford University Press (OUP) ; 2012
    In:  Journal of Industrial Microbiology and Biotechnology Vol. 39, No. 5 ( 2012-05-01), p. 789-797
    Details
    In: Journal of Industrial Microbiology and Biotechnology, Oxford University Press (OUP), Vol. 39, No. 5 ( 2012-05-01), p. 789-797
    Abstract: The waste materials from the carob processing industry are a potential resource for second-generation bioethanol production. These by-products are small carob kibbles with a high content of soluble sugars (45–50%). Batch and fed-batch Saccharomyces cerevisiae fermentations of high density sugar from carob pods were analyzed in terms of the kinetics of sugars consumption and ethanol inhibition. In all the batch runs, 90–95% of the total sugar was consumed and transformed into ethanol with a yield close to the theoretical maximum (0.47–0.50 g/g), and a final ethanol concentration of 100–110 g/l. In fed-batch runs, fresh carob extract was added when glucose had been consumed. This addition and the subsequent decrease of ethanol concentrations by dilution increased the final ethanol production up to 130 g/l. It seems that invertase activity and yeast tolerance to ethanol are the main factors to be controlled in carob fermentations. The efficiency of highly concentrated carob fermentation makes it a very promising process for use in a second-generation ethanol biorefinery.
    Type of Medium: Online Resource
    ISSN: 1476-5535 , 1367-5435
    URL: Article
    DOI: 10.1007/s10295-011-1079-4
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
    detail.hit.zdb_id: 1482484-X
    SSG: 12
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  • 8
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    DDDR-15. SPIDER VENOM MOLECULES IMPAIR HUMAN GLIOMA CELLS MIGRATION: POTENTIAL APPLICATION IN CANCER THERAPY
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii101-vii102
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_7 ( 2022-11-14), p. vii101-vii102
    Abstract: Gliomas correspond to approximately 80% of malignant neoplasms of the central nervous system. Due to its aggressiveness, there is a growing need to seek new strategies to control the disease. The components of spider venoms are stable peptides with high specificity against biological molecular targets of therapeutic relevance. It has already been demonstrated by our group that two subfractions (SFs) isolated from the Phoneutria nigriventer spider venom (PnV) (called SF1 and SF11) can delay the migration of glioblastoma (GB) well-established cell lineage in invasions assays. Therefore, the present study aimed to evaluate the responsiveness of samples collected from Brazilian patients with a presumptive diagnosis of glioma (high and low grades), to PnV SFs, in order to contribute to the development of new drugs. After patient consent, 13 samples were collected for cultivation and attempt to reach the tenth passage, to ensure the establishment of the lineage. Four lineages were established: J01 and N07 – glioblastoma (high grade); C03 and L09 – astrocytoma and oligodendroglioma (low grade) respectively. Cells were incubated for 48 hours with SF1 and SF11, during the scratch wound-healing assay. The results demonstrated that the SFs, mainly SF11 (which proved to be a pure peptide with 1603,88 Da, sequenced as PyrKKDKKDKFY–GLM–NH2), harmed the migration of all these samples when compared to the control group. In addition, initial data with J01 lineage demonstrated that migration was also affected during the transwell invasion assay; as well as ROCK protein, involved in control of cell migration, was decreased (demonstrated by western blot) by both SFs, suggesting that ROCK is involved in the mechanism of the components. Ongoing tests continue to establish other samples collected so that the tests described above will also be carried out. These results will contribute to the development of new therapies against these tumors. Support: FAPESP #2019/10003-3.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac209.380
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 9
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    The Sexual Pleasure Scale
    Oxford University Press (OUP) ; 2017
    In:  The Journal of Sexual Medicine Vol. 14, No. Supplement_4b ( 2017-05-01), p. e308-e308
    Details
    In: The Journal of Sexual Medicine, Oxford University Press (OUP), Vol. 14, No. Supplement_4b ( 2017-05-01), p. e308-e308
    Type of Medium: Online Resource
    ISSN: 1743-6109 , 1743-6095
    URL: Article
    DOI: 10.1016/j.jsxm.2017.04.480
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
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  • 10
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    Initial Validation of the Sexual Pleasure Scale in Clinical and Non-Clinical Samples of Partnered Heterosexual People
    Oxford University Press (OUP) ; 2016
    In:  The Journal of Sexual Medicine Vol. 13, No. 9 ( 2016-09), p. 1408-1413
    Details
    In: The Journal of Sexual Medicine, Oxford University Press (OUP), Vol. 13, No. 9 ( 2016-09), p. 1408-1413
    Type of Medium: Online Resource
    ISSN: 1743-6095
    URL: Article
    DOI: 10.1016/j.jsxm.2016.06.010
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
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