The Barretos Cancer Hospital Animal Facility: Implementation and Results of a Dedicated Platform for Preclinical Oncology Models

Teixeira, Silvia A.; Luzzi, Mayara de Cássia; Martín, Ángel G.; Duarte, Terence; Leal, Mônica de Oliveira; Teixeira, Gustavo Ramos; Reis, Monise Tadin; Almeida, Carlos; Santos, K. M. O. dos; Melendez, Matias Eliseo; Silva, Diego da Cunha Silveira Alves da; Bernécule, Priscila Neves; Firmino, Higor Vinicius Lourenço; Alves, Ana Laura V.; Guimarães, Denise Peixoto; Borduqui, João Vitor; Laus, Ana Carolina; Mançano, Bruna Minniti; Reis, Rui Manuel

doi:10.3390/vetsci9110636

Cited by 4 publications

(4 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The combination of TMZ with carbonic anhydrase inhibitors [52], including Indisulam [20], results in increased TMZ efficacy and indicates a promising strategy toward more effective treatments. In addition, Indisulam has already been tested in combination with another chemo-and radiotherapeutic agents in vitro, in vivo, and clinical studies, showing promising results as an adjuvant strategy [20,21,[83][84][85]. Despite the limitation of working with established cell lines and in vitro models, several studies and different research groups with the purpose of better understanding the tumor biology of pediatric glioblastoma have already used the SF188 and KNS-42 cell lines, being two reliable models of investigation of this tumor subtype.…”

Section: Discussionmentioning

confidence: 99%

Indisulam Reduces Viability and Regulates Apoptotic Gene Expression in Pediatric High-Grade Glioma Cells

et al. 2022

Self Cite

View full text Add to dashboard Cite

Pediatric high-grade glioma (pHGG) is one of the most aggressive brain tumors. Treatment includes surgery, radiotherapy, chemotherapy, or combination therapy in children older than 3–5 years of age. These devastating tumors are influenced by the hypoxic microenvironment that coordinatively increases the expression of carbonic anhydrases (CA9 and CA12) that are involved in pH regulation, metabolism, cell invasion, and resistance to therapy. The synthetic sulphonamide Indisulam is a potent inhibitor of CAs. The aim of this study was to evaluate the effects of Indisulam on CA9 and CA12 enzymes in pHGG cell lines. Our results indicated that, under hypoxia, the gene and protein expression of CA9 and CA12 are increased in pHGG cells. The functional effects of Indisulam on cell proliferation, clonogenic capacity, and apoptosis were measured in vitro. CA9 and CA12 gene and protein expression were analyzed by RT-PCR and western blot. The treatment with Indisulam significantly reduced cell proliferation (dose-time-dependent) and clonogenic capacity (p < 0.05) and potentiated the effect of apoptosis (p < 0.01). Indisulam promoted an imbalance in the anti-apoptotic BCL2 and pro-apoptotic BAX protein expression. Our results demonstrate that Indisulam contributes to apoptosis via imbalance of apoptotic proteins (BAX/BCL2) and suggests a potential to overcome chemotherapy resistance caused by the regulation these proteins.

show abstract

Section: Discussionmentioning

confidence: 99%

Indisulam Reduces Viability and Regulates Apoptotic Gene Expression in Pediatric High-Grade Glioma Cells

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…To assess the tumorigenicity of HCB-541, subcutaneous injections of either 1 × 10 6 or 3 × 10 6 cells mixed with Matrigel® at a 1:1 (v/v) ratio were administered into the right flank of 8-week-old female NSG mice (NOD.Cg-Prkd cscid Il2rg tm1Wjl /SzJ, The Jackson Laboratory, USA), as previously described [ 14 ]. Tumor size was measured weekly with calypter, and volume was calculated using the formula: volume = length × width2/2.…”

Section: Methodsmentioning

confidence: 99%

Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line

Laus,

Gomes,

da Silva

et al. 2024

Human Cell

Self Cite

View full text Add to dashboard Cite

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

show abstract

“…Comercial human glioblastoma cells (U251 and U87), and primary glioblastoma cell line (HCB 151) derived from surgical biopsies obtained in the Neurosurgery Department of Barretos Cancer Hospital ( Martinho et al, 2013 ; Teixeira et al, 2022 ) (Sao Paulo, Brazil), acquired by the local ethics committee approval and the patient’s consent agreement, were kindly donated from Dr. Rui Reis, Barretos Cancer Hospital. Cell authentication was performed through short tandem repeat (STR) DNA typing, according to the International Reference Standard for Authentication of Human Cell Lines.…”

Section: Methodsmentioning

confidence: 99%

Using design of experiments (DoE) to optimize performance and stability of biomimetic cell membrane-coated nanostructures for cancer therapy

Ferreira

Miranda

Moreno

et al. 2023

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

Introduction: Cell membrane-covered biomimetic nanosystems have allowed the development of homologous nanostructures to bestow nanoparticles with enhanced biointerfacing capabilities. The stability of these structures, however, still represents a challenge for the scientific community. This study is aimed at developing and optimizing cell derived membrane-coated nanostructures upon applying design of experiments (DoE) to improve the therapeutic index by homotypic targeting in cancer cells.Methods: Important physicochemical features of the extracted cell membrane from tumoral cells were assessed by mass spectrometry-based proteomics. PLGA-based nanoparticles encapsulating temozolomide (TMZ NPs) were successfully developed. The coating technology applying the isolated U251 cell membrane (MB) was optimized using a fractional two-level three-factor factorial design. All the formulation runs were systematically characterized regarding their diameter, polydispersity index (PDI), and zeta potential (ZP). Experimental conditions generated by DoE were also subjected to morphological studies using negative-staining transmission electron microscopy (TEM). Its short-time stability was also assessed. MicroRaman and Fourier-Transform Infrared (FTIR) spectroscopies and Confocal microscopy were used as characterization techniques for evaluating the NP-MB nanostructures. Internalization studies were carried out to evaluate the homotypic targeting ability.Results and Discussion: The results have shown that nearly 80% of plasma membrane proteins were retained in the cell membrane vesicles after the isolation process, including key proteins to the homotypic binding. DoE analysis considering acquired TEM images reveals that condition run five should be the best-optimized procedure to produce the biomimetic cell-derived membrane-coated nanostructure (NP-MB). Storage stability for at least two weeks of the biomimetic system is expected once the original characteristics of diameter, PDI, and ZP, were maintained. Raman, FTIR, and confocal characterization results have shown the successful encapsulation of TMZ drug and provided evidence of the effective coating applying the MB. Cell internalization studies corroborate the proteomic data indicating that the optimized NP-MB achieved specific targeting of homotypic tumor cells. The structure should retain the complex biological functions of U251 natural cell membranes while exhibiting physicochemical properties suitable for effective homotypic recognition.Conclusion: Together, these findings provide coverage and a deeper understanding regarding the dynamics around extracted cell membrane and polymeric nanostructures interactions and an in-depth insight into the cell membrane coating technology and the development of optimized biomimetic and bioinspired nanostructured systems.

show abstract

The Barretos Cancer Hospital Animal Facility: Implementation and Results of a Dedicated Platform for Preclinical Oncology Models

Cited by 4 publications

References 58 publications

Indisulam Reduces Viability and Regulates Apoptotic Gene Expression in Pediatric High-Grade Glioma Cells

Indisulam Reduces Viability and Regulates Apoptotic Gene Expression in Pediatric High-Grade Glioma Cells

Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line

Using design of experiments (DoE) to optimize performance and stability of biomimetic cell membrane-coated nanostructures for cancer therapy

Contact Info

Product

Resources

About