1.Assessing 18F‑FDG PET/CT Uptake and its Correlation with Molecular Biomarkers in Penile Cancer
André SALAZAR ; Eduardo Paulino JÚNIOR ; Diego F. SÁNCHEZ ; Aízis Tatiane Santos GONÇALVES ; Renata Toscano SIMÕES ; Raul SILVA‑FILHO ; João V. S. RAIMUNDO ; Yuri V. C. SOARES ; Matheus L. MARINHO ; Antonio L. CUBILLA ; Marcelo MAMEDE
Nuclear Medicine and Molecular Imaging 2025;59(2):135-146
Background:
Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes.
Objective:
This study investigates the effectiveness of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG.
Methods:
Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value (SUVmax ) and volumetric SUV (SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA.
Results:
Warty SCC showed the highest SUV value and significant differences in SUVmax (p=0.015). Higher SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant.
Conclusions
The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.
2.Assessing 18F‑FDG PET/CT Uptake and its Correlation with Molecular Biomarkers in Penile Cancer
André SALAZAR ; Eduardo Paulino JÚNIOR ; Diego F. SÁNCHEZ ; Aízis Tatiane Santos GONÇALVES ; Renata Toscano SIMÕES ; Raul SILVA‑FILHO ; João V. S. RAIMUNDO ; Yuri V. C. SOARES ; Matheus L. MARINHO ; Antonio L. CUBILLA ; Marcelo MAMEDE
Nuclear Medicine and Molecular Imaging 2025;59(2):135-146
Background:
Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes.
Objective:
This study investigates the effectiveness of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG.
Methods:
Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value (SUVmax ) and volumetric SUV (SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA.
Results:
Warty SCC showed the highest SUV value and significant differences in SUVmax (p=0.015). Higher SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant.
Conclusions
The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.
3.Biofabricated 3D Intestinal Models as an Alternative to AnimalBased Approaches for Drug Toxicity Assays
Larissa Bueno TOFANI ; Thayná Mendonc ¸a AVELINO ; Rafael Júnior de AZEVEDO ; Giovanna Blazutti ELIAS ; Melissa Dibbernn GANZERLA ; Maiara Ferreira TERRA ; Vanessa Kiraly Thomaz RODRIGUES ; Renata Santos RABELO ; Samarah Vargas HARB ; Ana Carolina Migliorini FIGUEIRA
Tissue Engineering and Regenerative Medicine 2025;22(2):181-194
BACKGROUND:
The main challenge in new drug development is accurately predicting the human response in preclinical models.
METHODS:
In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane.
RESULTS:
All models successfully replicated the structural and functional aspects of the intestinal barrier. The 3D bioprinted intestinal model, however, demonstrated superior epithelial barrier integrity enhanced tight junction formation, microvilli development, and increased mucus production. When subjected to Ibuprofen, the 3D bioprinted model provided a more predictive response, underscoring its potential as a reliable in vitro tool for drug toxicity testing.
CONCLUSION
Our 3D bioprinted intestinal model presents a robust and predictive platform for drug toxicity assessments, significantly reducing the need for animal testing. This model not only aligns with ethical testing protocols but also offers enhanced accuracy in predicting human responses, thereby advancing the field of drug development.
4.Biofabricated 3D Intestinal Models as an Alternative to AnimalBased Approaches for Drug Toxicity Assays
Larissa Bueno TOFANI ; Thayná Mendonc ¸a AVELINO ; Rafael Júnior de AZEVEDO ; Giovanna Blazutti ELIAS ; Melissa Dibbernn GANZERLA ; Maiara Ferreira TERRA ; Vanessa Kiraly Thomaz RODRIGUES ; Renata Santos RABELO ; Samarah Vargas HARB ; Ana Carolina Migliorini FIGUEIRA
Tissue Engineering and Regenerative Medicine 2025;22(2):181-194
BACKGROUND:
The main challenge in new drug development is accurately predicting the human response in preclinical models.
METHODS:
In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane.
RESULTS:
All models successfully replicated the structural and functional aspects of the intestinal barrier. The 3D bioprinted intestinal model, however, demonstrated superior epithelial barrier integrity enhanced tight junction formation, microvilli development, and increased mucus production. When subjected to Ibuprofen, the 3D bioprinted model provided a more predictive response, underscoring its potential as a reliable in vitro tool for drug toxicity testing.
CONCLUSION
Our 3D bioprinted intestinal model presents a robust and predictive platform for drug toxicity assessments, significantly reducing the need for animal testing. This model not only aligns with ethical testing protocols but also offers enhanced accuracy in predicting human responses, thereby advancing the field of drug development.
5.Assessing 18F‑FDG PET/CT Uptake and its Correlation with Molecular Biomarkers in Penile Cancer
André SALAZAR ; Eduardo Paulino JÚNIOR ; Diego F. SÁNCHEZ ; Aízis Tatiane Santos GONÇALVES ; Renata Toscano SIMÕES ; Raul SILVA‑FILHO ; João V. S. RAIMUNDO ; Yuri V. C. SOARES ; Matheus L. MARINHO ; Antonio L. CUBILLA ; Marcelo MAMEDE
Nuclear Medicine and Molecular Imaging 2025;59(2):135-146
Background:
Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes.
Objective:
This study investigates the effectiveness of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG.
Methods:
Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value (SUVmax ) and volumetric SUV (SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA.
Results:
Warty SCC showed the highest SUV value and significant differences in SUVmax (p=0.015). Higher SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant.
Conclusions
The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.
6.Biofabricated 3D Intestinal Models as an Alternative to AnimalBased Approaches for Drug Toxicity Assays
Larissa Bueno TOFANI ; Thayná Mendonc ¸a AVELINO ; Rafael Júnior de AZEVEDO ; Giovanna Blazutti ELIAS ; Melissa Dibbernn GANZERLA ; Maiara Ferreira TERRA ; Vanessa Kiraly Thomaz RODRIGUES ; Renata Santos RABELO ; Samarah Vargas HARB ; Ana Carolina Migliorini FIGUEIRA
Tissue Engineering and Regenerative Medicine 2025;22(2):181-194
BACKGROUND:
The main challenge in new drug development is accurately predicting the human response in preclinical models.
METHODS:
In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane.
RESULTS:
All models successfully replicated the structural and functional aspects of the intestinal barrier. The 3D bioprinted intestinal model, however, demonstrated superior epithelial barrier integrity enhanced tight junction formation, microvilli development, and increased mucus production. When subjected to Ibuprofen, the 3D bioprinted model provided a more predictive response, underscoring its potential as a reliable in vitro tool for drug toxicity testing.
CONCLUSION
Our 3D bioprinted intestinal model presents a robust and predictive platform for drug toxicity assessments, significantly reducing the need for animal testing. This model not only aligns with ethical testing protocols but also offers enhanced accuracy in predicting human responses, thereby advancing the field of drug development.
7.Assessing 18F‑FDG PET/CT Uptake and its Correlation with Molecular Biomarkers in Penile Cancer
André SALAZAR ; Eduardo Paulino JÚNIOR ; Diego F. SÁNCHEZ ; Aízis Tatiane Santos GONÇALVES ; Renata Toscano SIMÕES ; Raul SILVA‑FILHO ; João V. S. RAIMUNDO ; Yuri V. C. SOARES ; Matheus L. MARINHO ; Antonio L. CUBILLA ; Marcelo MAMEDE
Nuclear Medicine and Molecular Imaging 2025;59(2):135-146
Background:
Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes.
Objective:
This study investigates the effectiveness of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG.
Methods:
Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value (SUVmax ) and volumetric SUV (SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA.
Results:
Warty SCC showed the highest SUV value and significant differences in SUVmax (p=0.015). Higher SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant.
Conclusions
The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.
8.Biofabricated 3D Intestinal Models as an Alternative to AnimalBased Approaches for Drug Toxicity Assays
Larissa Bueno TOFANI ; Thayná Mendonc ¸a AVELINO ; Rafael Júnior de AZEVEDO ; Giovanna Blazutti ELIAS ; Melissa Dibbernn GANZERLA ; Maiara Ferreira TERRA ; Vanessa Kiraly Thomaz RODRIGUES ; Renata Santos RABELO ; Samarah Vargas HARB ; Ana Carolina Migliorini FIGUEIRA
Tissue Engineering and Regenerative Medicine 2025;22(2):181-194
BACKGROUND:
The main challenge in new drug development is accurately predicting the human response in preclinical models.
METHODS:
In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane.
RESULTS:
All models successfully replicated the structural and functional aspects of the intestinal barrier. The 3D bioprinted intestinal model, however, demonstrated superior epithelial barrier integrity enhanced tight junction formation, microvilli development, and increased mucus production. When subjected to Ibuprofen, the 3D bioprinted model provided a more predictive response, underscoring its potential as a reliable in vitro tool for drug toxicity testing.
CONCLUSION
Our 3D bioprinted intestinal model presents a robust and predictive platform for drug toxicity assessments, significantly reducing the need for animal testing. This model not only aligns with ethical testing protocols but also offers enhanced accuracy in predicting human responses, thereby advancing the field of drug development.
9.Assessing 18F‑FDG PET/CT Uptake and its Correlation with Molecular Biomarkers in Penile Cancer
André SALAZAR ; Eduardo Paulino JÚNIOR ; Diego F. SÁNCHEZ ; Aízis Tatiane Santos GONÇALVES ; Renata Toscano SIMÕES ; Raul SILVA‑FILHO ; João V. S. RAIMUNDO ; Yuri V. C. SOARES ; Matheus L. MARINHO ; Antonio L. CUBILLA ; Marcelo MAMEDE
Nuclear Medicine and Molecular Imaging 2025;59(2):135-146
Background:
Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes.
Objective:
This study investigates the effectiveness of 18F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of 18F-FDG.
Methods:
Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis wasperformed using the maximum standardized uptake value (SUVmax ) and volumetric SUV (SUV2SD ). Tissue expressionanalysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA.
Results:
Warty SCC showed the highest SUV value and significant differences in SUVmax (p=0.015). Higher SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative,GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value significantly differed for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant.
Conclusions
The study highlights correlations between the uptake of 18F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.
10.Biofabricated 3D Intestinal Models as an Alternative to AnimalBased Approaches for Drug Toxicity Assays
Larissa Bueno TOFANI ; Thayná Mendonc ¸a AVELINO ; Rafael Júnior de AZEVEDO ; Giovanna Blazutti ELIAS ; Melissa Dibbernn GANZERLA ; Maiara Ferreira TERRA ; Vanessa Kiraly Thomaz RODRIGUES ; Renata Santos RABELO ; Samarah Vargas HARB ; Ana Carolina Migliorini FIGUEIRA
Tissue Engineering and Regenerative Medicine 2025;22(2):181-194
BACKGROUND:
The main challenge in new drug development is accurately predicting the human response in preclinical models.
METHODS:
In this study, we developed three different intestinal barrier models using advanced biofabrication techniques: (i) a manual model containing Caco-2 and HT-29 cells on a collagen bed, (ii) a manual model with a Caco-2/HT-29 layer on a HDFn-laden collagen layer, and (iii) a 3D bioprinted model incorporating both cellular layers. Each model was rigorously tested for its ability to simulate a functional intestinal membrane.
RESULTS:
All models successfully replicated the structural and functional aspects of the intestinal barrier. The 3D bioprinted intestinal model, however, demonstrated superior epithelial barrier integrity enhanced tight junction formation, microvilli development, and increased mucus production. When subjected to Ibuprofen, the 3D bioprinted model provided a more predictive response, underscoring its potential as a reliable in vitro tool for drug toxicity testing.
CONCLUSION
Our 3D bioprinted intestinal model presents a robust and predictive platform for drug toxicity assessments, significantly reducing the need for animal testing. This model not only aligns with ethical testing protocols but also offers enhanced accuracy in predicting human responses, thereby advancing the field of drug development.

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