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Article ; Online: P-glycoprotein and cancer

Carlos Pilotto Heming / Wanjiru Muriithi / Lucy Wanjiku Macharia / Paulo Niemeyer Filho / Vivaldo Moura-Neto / Veronica Aran

Heliyon, Vol 8, Iss 10, Pp e11171- (2022)

what do we currently know?

2022

Abstract: Acquired resistance during cancer treatment is unfortunately a frequent event. There are several reasons for this, including the ability of the ATP-binding cassette transporters (ABC transporters), which are integral membrane proteins, to export ... ...

Abstract	Acquired resistance during cancer treatment is unfortunately a frequent event. There are several reasons for this, including the ability of the ATP-binding cassette transporters (ABC transporters), which are integral membrane proteins, to export chemotherapeutic molecules from the interior of the tumor cells. One important member of this family is the protein known as Permeability Glycoprotein (P-Glycoprotein, P-gp or ABCB1). Its clinical relevance relies mainly on the fact that the inhibition of P-gp and other ABC transporters could result in the reversal of the multidrug resistance (MDR) phenotype in some patients. Recently, other roles apart from being a key player in MDR, have emerged for P-gp. Therefore, this review discusses the relationship between P-gp and MDR, in addition to the possible role of this protein as a biomarker in cancer.
Keywords	MDR phenotype ; P-glycoprotein ; ABCB1 ; Cancer biomarkers ; ABC transporters ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	610
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Use of Liquid Biopsy in the Molecular Analysis of Plasma Compared to the Tumour Tissue from a Patient with Brain Metastasis

Veronica Aran / Vinicius Mansur Zogbi / Renan Lyra Miranda / Felipe Andreiuolo / Nathalie Henriques Silva Canedo / Carolina Victor Nazaré / Paulo Niemeyer Filho / Vivaldo Moura Neto

Medicina, Vol 59, Iss 459, p

A Case Report

2023 Volume 459

Abstract: Different cancers have multiple genetic mutations, which vary depending on the affected tumour tissue. Small biopsies may not always represent all the genetic landscape of the tumour. To improve the chances of identifying mutations at different disease ... ...

Abstract	Different cancers have multiple genetic mutations, which vary depending on the affected tumour tissue. Small biopsies may not always represent all the genetic landscape of the tumour. To improve the chances of identifying mutations at different disease stages (early, during the disease course, and refractory stage), liquid biopsies offer an advantage to traditional tissue biopsy. In addition, it is possible to detect mutations related to metastatic events depending on the cancer types analysed as will be discussed in this case report, which describes a patient with brain metastasis and lung cancer that harboured K-RAS mutations both in the brain tumour and in the ctDNA present in the bloodstream.
Keywords	brain metastases ; lung hepatoid adenocarcinoma ; K-RAS ; liquid biopsy ; ddPCR ; Medicine (General) ; R5-920
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Short-Term Functional and Morphological Changes in the Primary Cultures of Trigeminal Ganglion Cells

Carla Pires Veríssimo / Lionete Gall Acosta Filha / Fábio Jorge Moreira da Silva / Harrison Westgarth / Juliana De Mattos Coelho Aguiar / Bruno Pontes / Vivaldo Moura-Neto / Parisa Gazerani / Marcos F. DosSantos

Current Issues in Molecular Biology, Vol 44, Iss 84, Pp 1257-

2022 Volume 1272

Abstract: Several studies have proved that glial cells, as well as neurons, play a role in pain pathophysiology. Most of these studies have focused on the contribution of central glial cells (e.g., microglia and astrocytes) to neuropathic pain. Likewise, some ... ...

Abstract	Several studies have proved that glial cells, as well as neurons, play a role in pain pathophysiology. Most of these studies have focused on the contribution of central glial cells (e.g., microglia and astrocytes) to neuropathic pain. Likewise, some works have suggested that peripheral glial cells, particularly satellite glial cells (SGCs), and the crosstalk between these cells and the sensory neurons located in the peripheral ganglia, play a role in the phenomenon that leads to pain. Nonetheless, the study of SGCs may be challenging, as the validity of studying those cells in vitro is still controversial. In this study, a research protocol was developed to examine the potential use of primary mixed neuronal–glia cell cultures obtained from the trigeminal ganglion cells (TGCs) of neonate mice (P10–P12). Primary cultures were established and analyzed at 4 h, 24 h, and 48 h. To this purpose, phase contrast microscopy, immunocytochemistry with antibodies against anti-βIII-tubulin and Sk3, scanning electron microscopy, and time-lapse photography were used. The results indicated the presence of morphological changes in the cultured SGCs obtained from the TGCs. The SGCs exhibited a close relationship with neurons. They presented a round shape in the first 4 h, and a more fusiform shape at 24 h and 48 h of culture. On the other hand, neurons changed from a round shape to a more ramified shape from 4 h to 48 h. Intriguingly, the expression of SK3, a marker of the SGCs, was high in all samples at 4 h, with some cells double-staining for SK3 and βIII-tubulin. The expression of SK3 decreased at 24 h and increased again at 48 h in vitro. These results confirm the high plasticity that the SGCs may acquire in vitro. In this scenario, the authors hypothesize that, at 4 h, a group of the analyzed cells remained undifferentiated and, therefore, were double-stained for SK3 and βIII-tubulin. After 24 h, these cells started to differentiate into SCGs, which was clearer at 48 h in the culture. Mixed neuronal–glial TGC cultures might ...
Keywords	primary cell cultures ; trigeminal ganglia ; neurons ; satellite glial cells ; orofacial pain ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Case report

Patricia P. Garcez / André Guasti / Nina Ventura / Luiza Mendonça Higa / Felipe Andreiuolo / Gabriella Pinheiro A. de Freitas / Liane de Jesus Ribeiro / Richard Araújo Maia / Sheila Maria Barbosa de Lima / Adriana de Souza Azevedo / Waleska Dias Schwarcz / Elena Cristina Caride / Leila Chimelli / Luiz Gustavo Dubois / Orlando da Costa Ferreira Júnior / Amilcar Tanuri / Vivaldo Moura-Neto / Paulo Niemeyer

Frontiers in Medicine, Vol

Regression of Glioblastoma after flavivirus infection

2023 Volume 10

Abstract: Glioblastoma is the most frequent and aggressive primary brain cancer. In preclinical studies, Zika virus, a flavivirus that triggers the death of glioblastoma stem-like cells. However, the flavivirus oncolytic activity has not been demonstrated in human ...

Abstract	Glioblastoma is the most frequent and aggressive primary brain cancer. In preclinical studies, Zika virus, a flavivirus that triggers the death of glioblastoma stem-like cells. However, the flavivirus oncolytic activity has not been demonstrated in human patients. Here we report a glioblastoma patient who received the standard of care therapy, including surgical resection, radiotherapy and temozolomide. However, shortly after the tumor mass resection, the patient was clinically diagnosed with a typical arbovirus-like infection, during a Zika virus outbreak in Brazil. Following the infection resolution, the glioblastoma regressed, and no recurrence was observed. This clinical response continues 6 years after the glioblastoma initial diagnosis.
Keywords	glioblastoma ; flavivirus ; oncolytic virus ; ZIKV ; DENV ; immunovirotherapy ; Medicine (General) ; R5-920
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Osteoarthritic Synovial Fluid Modulates Cell Phenotype and Metabolic Behavior In Vitro

Eduardo Branco de Sousa / Gilson Costa dos Santos Junior / Ramon Pinheiro Aguiar / Rafaela da Costa Sartore / Ana Carolina Leal de Oliveira / Fabio Ceneviva Lacerda Almeida / Vivaldo Moura Neto / Diego Pinheiro Aguiar

Stem Cells International, Vol

2019 Volume 2019

Abstract: Synovial fluid holds a population of mesenchymal stem cells (MSC) that could be used for clinical treatment. Our goal was to characterize the inflammatory and metabolomic profile of the synovial fluid from osteoarthritic patients and to identify its ... ...

Abstract	Synovial fluid holds a population of mesenchymal stem cells (MSC) that could be used for clinical treatment. Our goal was to characterize the inflammatory and metabolomic profile of the synovial fluid from osteoarthritic patients and to identify its modulatory effect on synovial fluid cells. Synovial fluid was collected from non-OA and OA patients, which was centrifuged to isolate cells. Cells were cultured for 21 days, characterized with specific markers for MSC, and exposed to a specific cocktail to induce chondrogenic, osteogenic, and adipogenic differentiation. Then, we performed a MTT assay exposing SF cells from non-OA and OA patients to a medium containing non-OA and OA synovial fluid. Synovial fluid from non-OA and OA patients was submitted to ELISA to evaluate BMP-2, BMP-4, IL-6, IL-10, TNF-α, and TGF-β1 concentrations and to a metabolomic evaluation using 1H-NMR. Synovial fluid cells presented spindle-shaped morphology in vitro. Samples from OA patients formed a higher number of colonies than the ones from non-OA patients. After 21 days, the colony-forming cells from OA patients differentiated into the three mesenchymal cell lineages, under the appropriated induction protocols. Synovial fluid cells increased its metabolic activity after being exposed to the OA synovial fluid. ELISA assay showed that OA synovial fluid samples presented higher concentration of IL-10 and TGF-β1 than the non-OA, while the NMR showed that OA synovial fluid presents higher concentrations of glucose and glycerol. In conclusion, SFC activity is modulated by OA synovial fluid, which presents higher concentration of IL-10, TGF-β, glycerol, and glucose.
Keywords	Internal medicine ; RC31-1245
Subject code	616 ; 532
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Neuromechanisms of SARS-CoV-2

Marcos F. DosSantos / Sylvie Devalle / Veronica Aran / Daniela Capra / Natália Roberta Roque / Juliana de Mattos Coelho-Aguiar / Tânia Cristina Leite de Sampaio e Spohr / Janice Gonçalves Subilhaga / Cláudia Maria Pereira / Isabella D'Andrea Meira / Paulo Niemeyer Soares Filho / Vivaldo Moura-Neto

Frontiers in Neuroanatomy, Vol

A Review

2020 Volume 14

Abstract: Recent studies have suggested the neuroinvasive potential of severe acute respiratory coronavirus 2 (SARS-CoV-2). Notably, neuroinvasiveness might be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). Some studies have demonstrated ... ...

Abstract	Recent studies have suggested the neuroinvasive potential of severe acute respiratory coronavirus 2 (SARS-CoV-2). Notably, neuroinvasiveness might be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). Some studies have demonstrated that synapse-connected routes may enable coronaviruses to access the central nervous system (CNS). However, evidence related to the presence of SARS-CoV-2 in the CNS, its direct impact on the CNS, and the contribution to symptoms suffered, remain sparse. Here, we review the current literature that indicates that SARS-CoV-2 can invade the nervous system. We also describe the neural circuits that are potentially affected by the virus and their possible role in the progress of COVID-19. In addition, we propose several strategies to understand, diagnose, and treat the neurological symptoms of COVID-19.
Keywords	SARS-CoV-2 ; COVID-19 ; central nervous system ; peripheral nervous system ; anosmia ; dysgeusia ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Human anatomy ; QM1-695 ; covid19
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: miRNAs

Cláudia Maria Pereira / Dayany Sehnem / Estevão Oliveira da Fonseca / Heráclito Fernando Gurgel Barboza / Antônio Carlos Pires de Carvalho / Alexandre F. M. DaSilva / Vivaldo Moura-Neto / Marcos F. DosSantos

BioMed Research International, Vol

Important Targets for Oral Cancer Pain Research

2017 Volume 2017

Abstract: Pain is a symptom shared by an incredible number of diseases. It is also one of the primary conditions that prompt individuals to seek medical treatment. Head and neck squamous cell carcinoma (HNSCC) corresponds to a heterogeneous disease that may arise ... ...

Abstract	Pain is a symptom shared by an incredible number of diseases. It is also one of the primary conditions that prompt individuals to seek medical treatment. Head and neck squamous cell carcinoma (HNSCC) corresponds to a heterogeneous disease that may arise from many distinct structures of a large, highly complex, and intricate region. HNSCC affects a great number of patients worldwide and is directly associated with chronic pain, which is especially prominent during the advanced stages of oral squamous cell carcinoma (OSCC), an anatomical and clinical subtype that corresponds to the great majority oral cancers. Although the cellular and molecular bases of oral cancer pain have not been fully established yet, the results of recent studies suggest that different epigenetic mechanisms may contribute to this process. For instance, there is strong scientific evidence that microRNAs (miRNAs), small RNA molecules that do not encode proteins, might act by regulating the mechanisms underlying cancer-related pain. Among the miRNAs that could possibly interfere in pain-signaling pathways, miR-125b, miR-181, and miR-339 emerge as some of the most promising candidates. In fact, such molecules apparently contribute to inflammatory pain. Moreover, these molecules possibly influence the activity of endogenous pain control systems (e.g., opioidergic and serotonergic systems), which could ultimately result in peripheral and central sensitization, central nervous system (CNS) phenomena innately associated with chronic pain. This review paper focuses on the current scientific knowledge regarding the involvement of miRNAs in cancer pain, with special attention dedicated to OSCC-related pain.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: 5-Fluorouracil Induces Enteric Neuron Death and Glial Activation During Intestinal Mucositis via a S100B-RAGE-NFκB-Dependent Pathway

Deiziane V. S. Costa / Ana C. Bon-Frauches / Angeline M. H. P. Silva / Roberto C. P. Lima-Júnior / Conceição S. Martins / Renata F. C. Leitão / Gutierrez B. Freitas / Patricia Castelucci / David T. Bolick / Richard L. Guerrant / Cirle A. Warren / Vivaldo Moura-Neto / Gerly A. C. Brito

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 14

Abstract: Abstract 5-Fluorouracil (5-FU) is an anticancer agent whose main side effects include intestinal mucositis associated with intestinal motility alterations maybe due to an effect on the enteric nervous system (ENS), but the underlying mechanism remains ... ...

Abstract	Abstract 5-Fluorouracil (5-FU) is an anticancer agent whose main side effects include intestinal mucositis associated with intestinal motility alterations maybe due to an effect on the enteric nervous system (ENS), but the underlying mechanism remains unclear. In this report, we used an animal model to investigate the participation of the S100B/RAGE/NFκB pathway in intestinal mucositis and enteric neurotoxicity caused by 5-FU (450 mg/kg, IP, single dose). 5-FU induced intestinal damage observed by shortened villi, loss of crypt architecture and intense inflammatory cell infiltrate as well as increased GFAP and S100B co-expression and decreased HuC/D protein expression in the small intestine. Furthermore, 5-FU increased RAGE and NFκB NLS immunostaining in enteric neurons, associated with a significant increase in the nitrite/nitrate, IL-6 and TNF-α levels, iNOS expression and MDA accumulation in the small intestine. We provide evidence that 5-FU induces reactive gliosis and reduction of enteric neurons in a S100B/RAGE/NFκB-dependent manner, since pentamidine, a S100B inhibitor, prevented 5-FU-induced neuronal loss, enteric glia activation, intestinal inflammation, oxidative stress and histological injury.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Connective-Tissue Growth Factor (CTGF/CCN2) Induces Astrogenesis and Fibronectin Expression of Embryonic Neural Cells In Vitro.

Fabio A Mendes / Juliana M Coelho Aguiar / Suzana A Kahn / Alice H Reis / Luiz Gustavo Dubois / Luciana Ferreira Romão / Lais S S Ferreira / Hervé Chneiweiss / Vivaldo Moura Neto / José G Abreu

PLoS ONE, Vol 10, Iss 8, p e

2015 Volume 0133689

Abstract: Connective-tissue growth factor (CTGF) is a modular secreted protein implicated in multiple cellular events such as chondrogenesis, skeletogenesis, angiogenesis and wound healing. CTGF contains four different structural modules. This modular organization ...

Abstract	Connective-tissue growth factor (CTGF) is a modular secreted protein implicated in multiple cellular events such as chondrogenesis, skeletogenesis, angiogenesis and wound healing. CTGF contains four different structural modules. This modular organization is characteristic of members of the CCN family. The acronym was derived from the first three members discovered, cysteine-rich 61 (CYR61), CTGF and nephroblastoma overexpressed (NOV). CTGF is implicated as a mediator of important cell processes such as adhesion, migration, proliferation and differentiation. Extensive data have shown that CTGF interacts particularly with the TGFβ, WNT and MAPK signaling pathways. The capacity of CTGF to interact with different growth factors lends it an important role during early and late development, especially in the anterior region of the embryo. ctgf knockout mice have several cranio-facial defects, and the skeletal system is also greatly affected due to an impairment of the vascular-system development during chondrogenesis. This study, for the first time, indicated that CTGF is a potent inductor of gliogenesis during development. Our results showed that in vitro addition of recombinant CTGF protein to an embryonic mouse neural precursor cell culture increased the number of GFAP- and GFAP/Nestin-positive cells. Surprisingly, CTGF also increased the number of Sox2-positive cells. Moreover, this induction seemed not to involve cell proliferation. In addition, exogenous CTGF activated p44/42 but not p38 or JNK MAPK signaling, and increased the expression and deposition of the fibronectin extracellular matrix protein. Finally, CTGF was also able to induce GFAP as well as Nestin expression in a human malignant glioma stem cell line, suggesting a possible role in the differentiation process of gliomas. These results implicate ctgf as a key gene for astrogenesis during development, and suggest that its mechanism may involve activation of p44/42 MAPK signaling. Additionally, CTGF-induced differentiation of glioblastoma stem cells into a less-tumorigenic state could increase the chances of successful intervention, since differentiated cells are more vulnerable to cancer treatments.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Tamoxifen in combination with temozolomide induce a synergistic inhibition of PKC-pan in GBM cell lines

BalÃ§a-Silva, Joana / Ana Bela Sarmento-Ribeiro / AnÃ¡lia do Carmo / Diana Matias / Henrique GirÃ£o / Maria Celeste Lopes / Vivaldo Moura-Neto

BBA - General Subjects. 2015 Apr., v. 1850

2015

Abstract: Glioblastoma (GBM) is a highly proliferative, angiogenic grade IV astrocytoma that develops resistance to the alkylating agents used in chemotherapy, such as temozolomide (TMZ), which is considered the gold standard. The mean survival time for GBM ... ...

Abstract	Glioblastoma (GBM) is a highly proliferative, angiogenic grade IV astrocytoma that develops resistance to the alkylating agents used in chemotherapy, such as temozolomide (TMZ), which is considered the gold standard. The mean survival time for GBM patients is approximately 12months, increasing to 14.6months after TMZ treatment. The resistance of GBM to chemotherapy seems to be associated to genetic alterations and to the constitutive activation of several signaling pathways. Therefore, the combination of different drugs with different mechanisms of action may contribute to circumvent the chemoresistance of glioma cells. Here we describe the potential synergistic behavior of the therapeutic combination of tamoxifen (TMX), a known inhibitor of PKC, and TMZ in GBM.We used two GBM cell lines incubated in absence and presence of TMX and/or TMZ and measured cell viability, proliferation, apoptosis, cell cycle, migration ability, cytoskeletal organization and the phosphorylated amount of the p-PKC-pan.The combination of low doses of TMX with increasing doses of TMZ shows an increased antiproliferative and apoptotic effect compared to the effect with TMX alone.The combination of TMX and TMZ seems to potentiate the effect of each other. These alterations seem to be associated to a decrease in the phosphorylation status of PKC.We emphasize that TMX is an inhibitor of the p-PKC-pan and that these combination is more effective in the reduction of proliferation and in the increase of apoptosis than each drug alone, which presents a new therapeutic strategy in GBM treatment.
Keywords	apoptosis ; cell cycle ; cell viability ; cytoskeleton ; drug therapy ; mechanism of action ; patients ; phosphorylation ; protein kinase C ; signal transduction ; tamoxifen
Language	English
Dates of publication	2015-04
Size	p. 722-732.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	840755-1
ISSN	0304-4165
ISSN	0304-4165
DOI	10.1016/j.bbagen.2014.12.022
Database	NAL-Catalogue (AGRICOLA)

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