Adriana Roehe - Academia.edu (original) (raw)
Papers by Adriana Roehe
CONTEXTO: O carcinoma de células escamosas da mama é um câncer extremamente raro, representando c... more CONTEXTO: O carcinoma de células escamosas da mama é um câncer extremamente raro, representando cerca de 0,04% dos tumores malignos da mama. Até o momento, apenas um número limitado de casos da doença foi relatado, a maioria se apresentando clinicamente como um carcinoma de mama usual. RELATO DE CASO: Paciente feminina de 39 anos de idade se apresentando com grande abscesso de mama e sinais de sepse. Após debridamento cirúrgico da lesão, o exame histopatológico da cápsula do abscesso revelou a presença de carcinoma de células escamosas da mama. O tratamento definitivo do tumor foi uma mastectomia radical modificada com ressecção da lesão residual na mama direita. CONCLUSÃO: O presente caso, de apresentação incomum, demonstra como uma lesão aparentemente benigna, como um abscesso mamário, pode estar relacionada a uma neoplasia maligna oculta. Uma revisão da literatura a respeito do carcinoma de células escamosas de mama é apresentada.CONTEXT: Squamous cell carcinoma (SCC) of the brea...
Anais Brasileiros de Dermatologia
Cancer Detection and Prevention, 2006
Background: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a... more Background: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a risk factor for cancer in different populations. So far, the results have been controversial. Our purpose was to investigate the association of this polymorphism with breast carcinoma in women from Southern Brazil, a high-risk area for breast cancer. Methods: Blood samples collected from 118 women with primary breast carcinoma and from 202 female blood donors were analyzed through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. Results: The relative frequency of each allele was 0.75 for Arg and 0.25 for Pro in patients with cancer, and 0.62 for Arg and 0.38 for Pro in normal controls (P < 0.001). The Arg/Arg genotype was significantly associated with an increased risk for breast cancer (OR 2.9; 95% CI 1.43-3.6; P < 0.002). No correlation between the genotype distribution and specific prognostic predictors for the disease outcome was observed. Discussion: TP53 codon 72 polymorphism might be implicated in breast carcinogenesis, with the Arg/Arg genotype being associated with an increased susceptibility for this malignancy.
Cellular and Molecular Life Sciences
In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular res... more In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular responses to growth stimuli, damage, or inflammation. Due to only limited studies, the significance of ATF2 in colorectal cancer (CRC) is not well understood. We report that low ATF2 levels correlated with worse prognosis and tumor aggressiveness in CRC patients. NanoString gene expression and ChIP analysis confirmed trophoblast cell surface antigen 2 (TROP2) as a novel inhibitory ATF2 target gene. This inverse correlation was further observed in primary human tumor tissues. Immunostainings revealed that high intratumoral heterogeneity for ATF2 and TROP2 expression was sustained also in liver metastasis. Mechanistically, our in vitro data of CRISPR/Cas9-generated ATF2 knockout (KO) clones revealed that high TROP2 levels were critical for cell de-adhesion and increased cell migration without triggering EMT. TROP2 was enriched in filopodia and displaced Paxillin from adherens junctions. In vi...
Cancers
Cancer cells facilitate tumor growth by creating favorable tumor micro-environments (TME), alteri... more Cancer cells facilitate tumor growth by creating favorable tumor micro-environments (TME), altering homeostasis and immune response in the extracellular matrix (ECM) of surrounding tissue. A potential factor that contributes to TME generation and ECM remodeling is the cytoskeleton-associated human death-associated protein kinase 1 (DAPK1). Increased tumor cell motility and de-adhesion (thus, promoting metastasis), as well as upregulated plasminogen-signaling, are shown when functionally analyzing the DAPK1 ko-related proteome. However, the systematic investigation of how tumor cells actively modulate the ECM at the tissue level is experimentally challenging since animal models do not allow direct experimental access while artificial in vitro scaffolds cannot simulate the entire complexity of tissue systems. Here, we used the chorioallantoic membrane (CAM) assay as a natural, collagen-rich tissue model in combination with all-optical experimental access by multiphoton microscopy (MPM...
Revista Paulista de Pediatria, 2015
Jornal Brasileiro de Patologia e Medicina Laboratorial
1. Research Laboratory in Pathology, Graduate Program in Pathology, Federal University of Health ... more 1. Research Laboratory in Pathology, Graduate Program in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Brazil 2. Department of Gynecology and Obstetrics of Federal University, Rio Grande do Sul (UFRGS), Porto Alegre, Brazil 3. Research Laboratory in Molecular Biology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Rio Grande do Sul, Brazil 4. Department of Respiratory Medicine and Thoracic Surgery, Irmandade da Santa Casa de Misericordia de Porto Alegre, Rio Grande do Sul, Brazil 5. Department of Pathology, Graduate Programa in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
Expert Systems with Applications
Revista Brasileira de Farmacognosia
Journal of Digital Imaging
Revista da Associação Médica Brasileira
SUMMARY BACKGROUND: Asymmetric or heteropagus conjoined twins is a rare occurrence, with an incid... more SUMMARY BACKGROUND: Asymmetric or heteropagus conjoined twins is a rare occurrence, with an incidence of one case in 1-2 million. Conjoined twins are classified according to their symmetry, place of fusion, and grade of duplication. METHODS: We report here an extremely rare presentation of parasitic twins not described before. We describe macro and micro anatomic alterations and discuss the aspects of this peculiar presentation and the importance of prenatal diagnosis. RESULTS: The case of a twenty-three-year-old patient, with monochorionic, monoamniotic asymmetrically-conjoined twin pregnancy, discovered at 29 weeks of gestational age. We believe that this report calls attention to this presentation and the importance of prenatal care and management. The twins were delivered vaginally without life. The twins’ combined weight was 1.300 gr. They were bonded in the left cervical region. CONCLUSION: This report may help to find strategies for clinical decisions in future cases. Antepar...
Anais Principais do Simpósio Brasileiro de Computação Aplicada à Saúde (SBCAS 2020)
O diagnóstico em estágios iniciais normalmente resulta em um prognóstico melhor nos casos de cânc... more O diagnóstico em estágios iniciais normalmente resulta em um prognóstico melhor nos casos de câncer. Atualmente, a análise histopatológica e o padrão ouro para o diagnóstico, estadiamento e definição do tratamento de neoplasias de mama. Contudo, a técnica possui algumas restrições que dificultam o processo de análise pelo patologista, como diferentes protocolos de coloração, variações de coloração nas lâminas, e sobreposição de tecidos. Assim, a representação computacional das cores pode exercer uma influência significativa no comportamento dos modelos convolucionais. Desta forma, este estudo propõe uma análise comparativa da influência de quatro espaços de cores (RGB, HSV, YCrCb e LAB) para a segmentação multi-classe de Whole Slide Imaging (WSI) do câncer de mama. A metodologia proposta e composta por uma etapa de pré-processamento das WSI, data augmentation e multi- segmentação utilizando a arquitetura convolucional U-Net com uma ResNet-50 pré-treinada como codificador. Os resulta...
Systematic Reviews
Background Breast cancer is one of the most common malignancies in women worldwide, and one of th... more Background Breast cancer is one of the most common malignancies in women worldwide, and one of the leading causes of cancer-related death. Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic suppressors of the cytotoxic immune reaction. Some authors advocate that PD-L1 expression may help in breast cancer prognosis. Methods We will conduct a systematic review of observational or interventional studies evaluating the prognostic ability of PD-L1 expression levels in predicting positive clinical outcomes in Human Breast Cancer. A sensitive search strategy will be employed in MEDLINE, EMBASE, LILACS, The Grey Literature Report, OpenGrey, OAIster, and Cochrane CENTRAL. Two reviewers will independently screen all identified references for eligibility and extract data. The outcomes evaluated will be Overall Survival, Breast Cancer-specific Survival, Disease-free Survival, Recurrence-free Survival, Positive Lymph Node, and Distant Metastasis. The outcomes will be extra...
Journal of Cancer Research and Clinical Oncology
Purpose Enhancer of zeste homolog 2 (EZH2) is associated with epigenetic gene silencing and aggre... more Purpose Enhancer of zeste homolog 2 (EZH2) is associated with epigenetic gene silencing and aggressiveness in many tumor types. However, the prognostic impact of high EZH2 expression is controversially discussed for colorectal cancer. For this reason, we immunohistochemically analyzed EZH2 expression in 105 specimens from colon cancer patients separately for tumor center and invasion front. Methods All sections from tissue microarrays were evaluated manually and digitally using Definiens Tissue Studio software (TSS). To mirror-image the EZH2 status at the tumor invasion front, we treated HCT116 colon cancer cells with the EZH2 inhibitor 3-Deazaneplanocin A (DZNep) and studied the growth of in ovo xenografts in the chorioallantoic membrane (CAM) assay. Results We showed a significant decrease in EZH2 expression and the repressive H3K27me3 code at the tumor invasion front as supported by the TSS-constructed heatmaps. Loss of EZH2 at tumor invasion front, but not in tumor center was correlated with unfavorable prognosis and more advanced tumor stages. The observed cell cycle arrest in vitro and in vivo was associated with higher tumor aggressiveness. Xenografts formed by DZNep-treated HCT116 cells showed loosely packed tumor masses, infiltrative growth into the CAM, and high vessel density. Conclusion The differences in EZH2 expression between tumor center and invasion front as well as different scoring and cutoff values can most likely explain controversial literature data concerning the prognostic value of EZH2. Epigenetic therapies using EZH2 inhibitors have to be carefully evaluated for each specific tumor type, since alterations in cell differentiation might lead to unfavorable results.
Cell Death & Disease
Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and cont... more Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and contribute to chemotherapeutic resistance and disease relapse. It is well known that the survival of colorectal CSCs after 5fluorouracil (5-FU)-based therapy leads to cancer recurrence. Thus CSCs represent a promising drug target. Here, we designed and synthesized novel hybrid molecules linking 5-FU with the plant-derived compound thymoquinone (TQ) and tested the potential of individual compounds and their combination to eliminate colorectal CSCs. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. NanoString analysis revealed a unique signature of deregulated gene expression in response to the combination of TQ and 5-FU (Combi) and SARB treatment. Importantly, two principle stem cell regulatory pathways WNT/ß-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133+ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. In vivo xenografts on chicken eggs of SARB-treated HCT116 cells showed a prominent nuclear ß-Catenin and E-cadherin staining. This was in line with the reduced transcriptional activity of ß-Catenin and diminished cell adhesion under SARB exposure. In contrast to 5-FU, both, Combi and SARB treatment effectively reduced the angiogenic capacity of the remaining resistant tumor cells. Taken together, combination or hybridization of single compounds target simultaneously a broader spectrum of oncogenic pathways leading to an effective eradication of colorectal cancer cells.
Molecular and Cellular Biology / Genetics
CONTEXTO: O carcinoma de células escamosas da mama é um câncer extremamente raro, representando c... more CONTEXTO: O carcinoma de células escamosas da mama é um câncer extremamente raro, representando cerca de 0,04% dos tumores malignos da mama. Até o momento, apenas um número limitado de casos da doença foi relatado, a maioria se apresentando clinicamente como um carcinoma de mama usual. RELATO DE CASO: Paciente feminina de 39 anos de idade se apresentando com grande abscesso de mama e sinais de sepse. Após debridamento cirúrgico da lesão, o exame histopatológico da cápsula do abscesso revelou a presença de carcinoma de células escamosas da mama. O tratamento definitivo do tumor foi uma mastectomia radical modificada com ressecção da lesão residual na mama direita. CONCLUSÃO: O presente caso, de apresentação incomum, demonstra como uma lesão aparentemente benigna, como um abscesso mamário, pode estar relacionada a uma neoplasia maligna oculta. Uma revisão da literatura a respeito do carcinoma de células escamosas de mama é apresentada.CONTEXT: Squamous cell carcinoma (SCC) of the brea...
Anais Brasileiros de Dermatologia
Cancer Detection and Prevention, 2006
Background: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a... more Background: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a risk factor for cancer in different populations. So far, the results have been controversial. Our purpose was to investigate the association of this polymorphism with breast carcinoma in women from Southern Brazil, a high-risk area for breast cancer. Methods: Blood samples collected from 118 women with primary breast carcinoma and from 202 female blood donors were analyzed through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. Results: The relative frequency of each allele was 0.75 for Arg and 0.25 for Pro in patients with cancer, and 0.62 for Arg and 0.38 for Pro in normal controls (P < 0.001). The Arg/Arg genotype was significantly associated with an increased risk for breast cancer (OR 2.9; 95% CI 1.43-3.6; P < 0.002). No correlation between the genotype distribution and specific prognostic predictors for the disease outcome was observed. Discussion: TP53 codon 72 polymorphism might be implicated in breast carcinogenesis, with the Arg/Arg genotype being associated with an increased susceptibility for this malignancy.
Cellular and Molecular Life Sciences
In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular res... more In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular responses to growth stimuli, damage, or inflammation. Due to only limited studies, the significance of ATF2 in colorectal cancer (CRC) is not well understood. We report that low ATF2 levels correlated with worse prognosis and tumor aggressiveness in CRC patients. NanoString gene expression and ChIP analysis confirmed trophoblast cell surface antigen 2 (TROP2) as a novel inhibitory ATF2 target gene. This inverse correlation was further observed in primary human tumor tissues. Immunostainings revealed that high intratumoral heterogeneity for ATF2 and TROP2 expression was sustained also in liver metastasis. Mechanistically, our in vitro data of CRISPR/Cas9-generated ATF2 knockout (KO) clones revealed that high TROP2 levels were critical for cell de-adhesion and increased cell migration without triggering EMT. TROP2 was enriched in filopodia and displaced Paxillin from adherens junctions. In vi...
Cancers
Cancer cells facilitate tumor growth by creating favorable tumor micro-environments (TME), alteri... more Cancer cells facilitate tumor growth by creating favorable tumor micro-environments (TME), altering homeostasis and immune response in the extracellular matrix (ECM) of surrounding tissue. A potential factor that contributes to TME generation and ECM remodeling is the cytoskeleton-associated human death-associated protein kinase 1 (DAPK1). Increased tumor cell motility and de-adhesion (thus, promoting metastasis), as well as upregulated plasminogen-signaling, are shown when functionally analyzing the DAPK1 ko-related proteome. However, the systematic investigation of how tumor cells actively modulate the ECM at the tissue level is experimentally challenging since animal models do not allow direct experimental access while artificial in vitro scaffolds cannot simulate the entire complexity of tissue systems. Here, we used the chorioallantoic membrane (CAM) assay as a natural, collagen-rich tissue model in combination with all-optical experimental access by multiphoton microscopy (MPM...
Revista Paulista de Pediatria, 2015
Jornal Brasileiro de Patologia e Medicina Laboratorial
1. Research Laboratory in Pathology, Graduate Program in Pathology, Federal University of Health ... more 1. Research Laboratory in Pathology, Graduate Program in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Brazil 2. Department of Gynecology and Obstetrics of Federal University, Rio Grande do Sul (UFRGS), Porto Alegre, Brazil 3. Research Laboratory in Molecular Biology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Rio Grande do Sul, Brazil 4. Department of Respiratory Medicine and Thoracic Surgery, Irmandade da Santa Casa de Misericordia de Porto Alegre, Rio Grande do Sul, Brazil 5. Department of Pathology, Graduate Programa in Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
Expert Systems with Applications
Revista Brasileira de Farmacognosia
Journal of Digital Imaging
Revista da Associação Médica Brasileira
SUMMARY BACKGROUND: Asymmetric or heteropagus conjoined twins is a rare occurrence, with an incid... more SUMMARY BACKGROUND: Asymmetric or heteropagus conjoined twins is a rare occurrence, with an incidence of one case in 1-2 million. Conjoined twins are classified according to their symmetry, place of fusion, and grade of duplication. METHODS: We report here an extremely rare presentation of parasitic twins not described before. We describe macro and micro anatomic alterations and discuss the aspects of this peculiar presentation and the importance of prenatal diagnosis. RESULTS: The case of a twenty-three-year-old patient, with monochorionic, monoamniotic asymmetrically-conjoined twin pregnancy, discovered at 29 weeks of gestational age. We believe that this report calls attention to this presentation and the importance of prenatal care and management. The twins were delivered vaginally without life. The twins’ combined weight was 1.300 gr. They were bonded in the left cervical region. CONCLUSION: This report may help to find strategies for clinical decisions in future cases. Antepar...
Anais Principais do Simpósio Brasileiro de Computação Aplicada à Saúde (SBCAS 2020)
O diagnóstico em estágios iniciais normalmente resulta em um prognóstico melhor nos casos de cânc... more O diagnóstico em estágios iniciais normalmente resulta em um prognóstico melhor nos casos de câncer. Atualmente, a análise histopatológica e o padrão ouro para o diagnóstico, estadiamento e definição do tratamento de neoplasias de mama. Contudo, a técnica possui algumas restrições que dificultam o processo de análise pelo patologista, como diferentes protocolos de coloração, variações de coloração nas lâminas, e sobreposição de tecidos. Assim, a representação computacional das cores pode exercer uma influência significativa no comportamento dos modelos convolucionais. Desta forma, este estudo propõe uma análise comparativa da influência de quatro espaços de cores (RGB, HSV, YCrCb e LAB) para a segmentação multi-classe de Whole Slide Imaging (WSI) do câncer de mama. A metodologia proposta e composta por uma etapa de pré-processamento das WSI, data augmentation e multi- segmentação utilizando a arquitetura convolucional U-Net com uma ResNet-50 pré-treinada como codificador. Os resulta...
Systematic Reviews
Background Breast cancer is one of the most common malignancies in women worldwide, and one of th... more Background Breast cancer is one of the most common malignancies in women worldwide, and one of the leading causes of cancer-related death. Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic suppressors of the cytotoxic immune reaction. Some authors advocate that PD-L1 expression may help in breast cancer prognosis. Methods We will conduct a systematic review of observational or interventional studies evaluating the prognostic ability of PD-L1 expression levels in predicting positive clinical outcomes in Human Breast Cancer. A sensitive search strategy will be employed in MEDLINE, EMBASE, LILACS, The Grey Literature Report, OpenGrey, OAIster, and Cochrane CENTRAL. Two reviewers will independently screen all identified references for eligibility and extract data. The outcomes evaluated will be Overall Survival, Breast Cancer-specific Survival, Disease-free Survival, Recurrence-free Survival, Positive Lymph Node, and Distant Metastasis. The outcomes will be extra...
Journal of Cancer Research and Clinical Oncology
Purpose Enhancer of zeste homolog 2 (EZH2) is associated with epigenetic gene silencing and aggre... more Purpose Enhancer of zeste homolog 2 (EZH2) is associated with epigenetic gene silencing and aggressiveness in many tumor types. However, the prognostic impact of high EZH2 expression is controversially discussed for colorectal cancer. For this reason, we immunohistochemically analyzed EZH2 expression in 105 specimens from colon cancer patients separately for tumor center and invasion front. Methods All sections from tissue microarrays were evaluated manually and digitally using Definiens Tissue Studio software (TSS). To mirror-image the EZH2 status at the tumor invasion front, we treated HCT116 colon cancer cells with the EZH2 inhibitor 3-Deazaneplanocin A (DZNep) and studied the growth of in ovo xenografts in the chorioallantoic membrane (CAM) assay. Results We showed a significant decrease in EZH2 expression and the repressive H3K27me3 code at the tumor invasion front as supported by the TSS-constructed heatmaps. Loss of EZH2 at tumor invasion front, but not in tumor center was correlated with unfavorable prognosis and more advanced tumor stages. The observed cell cycle arrest in vitro and in vivo was associated with higher tumor aggressiveness. Xenografts formed by DZNep-treated HCT116 cells showed loosely packed tumor masses, infiltrative growth into the CAM, and high vessel density. Conclusion The differences in EZH2 expression between tumor center and invasion front as well as different scoring and cutoff values can most likely explain controversial literature data concerning the prognostic value of EZH2. Epigenetic therapies using EZH2 inhibitors have to be carefully evaluated for each specific tumor type, since alterations in cell differentiation might lead to unfavorable results.
Cell Death & Disease
Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and cont... more Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and contribute to chemotherapeutic resistance and disease relapse. It is well known that the survival of colorectal CSCs after 5fluorouracil (5-FU)-based therapy leads to cancer recurrence. Thus CSCs represent a promising drug target. Here, we designed and synthesized novel hybrid molecules linking 5-FU with the plant-derived compound thymoquinone (TQ) and tested the potential of individual compounds and their combination to eliminate colorectal CSCs. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. NanoString analysis revealed a unique signature of deregulated gene expression in response to the combination of TQ and 5-FU (Combi) and SARB treatment. Importantly, two principle stem cell regulatory pathways WNT/ß-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133+ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. In vivo xenografts on chicken eggs of SARB-treated HCT116 cells showed a prominent nuclear ß-Catenin and E-cadherin staining. This was in line with the reduced transcriptional activity of ß-Catenin and diminished cell adhesion under SARB exposure. In contrast to 5-FU, both, Combi and SARB treatment effectively reduced the angiogenic capacity of the remaining resistant tumor cells. Taken together, combination or hybridization of single compounds target simultaneously a broader spectrum of oncogenic pathways leading to an effective eradication of colorectal cancer cells.
Molecular and Cellular Biology / Genetics