RESUMO
PURPOSE: Evaluate the immunohistochemical expression of the ING3 in actinic cheilitis and squamous cell carcinoma of the lower lip. METHODS: Forty-five specimens of actinic cheilitis and 48 specimens of squamous cell carcinoma of the lower lip were submitted to immunohistochemical detection of ING3. The protein expression in different cellular sublocations was compared between the two groups, and associations with the clinicopathological variables were analyzed. A significance level of 5% was adopted for all tests. RESULTS: Deaths were significantly more frequent in tumors with a high histopathological risk score (p < 0.05). In actinic cheilitis, significant differences were found in the nucleus-cytoplasmic expression of ING3 and expression restricted to the cytoplasm with binary histopathological grading (p < 0.05). In squamous cell carcinoma of the lower lip, there was no statistically significant difference when comparing ING3 expressions with clinical and morphological parameters (p > 0.05). Nucleo-cytoplasmic ING3 expression was significantly lower in squamous cell carcinoma of the lower lip when compared to actinic cheilitis (p < 0.05) and the expression restricted to the cytoplasm was significantly higher in squamous cell carcinoma of the lower lip (p < 0.05). CONCLUSION: The results of this study suggest that there is a marked decrease in the nuclear expression of ING3 as malignant progression occurs, indicating an impaired tumor suppressor function of this protein in actinic cheilitis and squamous cell carcinoma of the lower lip.
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Núcleo Celular , Queilite , Proteínas de Homeodomínio , Neoplasias Labiais , Proteínas Supressoras de Tumor , Humanos , Neoplasias Labiais/patologia , Neoplasias Labiais/metabolismo , Queilite/patologia , Queilite/metabolismo , Proteínas Supressoras de Tumor/biossíntese , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/metabolismo , Adulto , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Carcinogênese , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Imuno-Histoquímica , Idoso de 80 Anos ou maisRESUMO
This systematic review aims to determine whether the presence of human papillomavirus (HPV) influences the immunohistochemical expression of programmed cell death-1 ligand (PD-L1) in oropharyngeal squamous cell carcinoma (OPSCC). PD-L1 immunohistochemical expression varies in OPSCC, and the presence of HPV is a plausible explanation for this variability. Comprehending these findings is crucial, as high PD-L1 expression in the tumor microenvironment of OPSCC can help identify patient subgroups that could be suitable for immunotherapy. Therefore, a systematic review was conducted following PRISMA guidelines (CRD42023437800). An electronic literature search was performed without time or language restrictions. The search included PubMed/MEDLINE, Embase, Scopus, Web of Science, https://clinictrials.gov, and relevant journals. A meta-analysis was performed using RStudio. Fourteen studies involving 1,629 participants were included. The sample consisted predominantly of males (81.26%) with a mean age of 58.3 years. Concerning clinical and pathological characteristics, the most frequently described anatomical location was the tonsils (68.54%), and most participants were either current or former smokers (78%) and alcohol users (79%). Advanced TNM IV was the most common stage. Regarding histopathological characteristics, HPV 16 was the only type mentioned, and half of the cases were detected through immunohistochemistry. The SP142 clone (35.7%) and the pattern of membrane immunostaining in tumor cells (71%) were the most commonly employed methods. The most prevalent findings were positive expression of PD-L1 (64.28%) and negative HPV status (57.14%). The association between PD-L1 positivity and HPV positivity (78.57%) was confirmed by meta-analysis. The conclusion was that HPV-positive status has an impact on immunohistochemical expression of PD-L1 in OPSCC.
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Antígeno B7-H1 , Carcinoma de Células Escamosas , Imuno-Histoquímica , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Antígeno B7-H1/análise , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Masculino , Feminino , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/patologia , Pessoa de Meia-Idade , Biomarcadores Tumorais/análise , PapillomaviridaeRESUMO
INTRODUCTION: The role of IMP3, CDK4, MDM2 and ß-catenin proteins in Enchondroma and Central Chondrosarcoma is not totally understood. The aim of this study is to evaluate the immunoexpression of these proteins, associating histological grade, clinical data and prognosis to these tumors. METHODS: This is a retrospective-analytical study of 32 Enchondroma and 70 Central Chondrosarcoma. RESULTS: IMP3, CDK4, MDM2 and ß-catenin expression was observed in 22.82 %, 13.82 %, 17.17 % and in 8.8 % of cases, respectively. All Enchondromas positive for these immunomarkers were located in short tubular bones. The positivity for these antibodies is directly proportional to Chondrosarcoma's histological grade increase. No difference was found between Enchondroma and Chondrosarcoma, Grade 1 for IMP3, CDK4 and ß-catenin positivity. Significant metastasis outcome was observed for IMP3, CDK4, MDM2 and death for MDM2 expression. CONCLUSION: IMP3, CDK4, MDM2 and ß-catenin expression in Enchondromas of short bones phenotypically characterizes these tumors. Their expression has not proven to be useful either as diagnostic markers of these neoplasms or in distinguishing between Enchondroma and Chondrosarcoma, Grade 1. The significant immunoexpression of IMP3, CDK4 and MDM2 in metastatic Chondrosarcoma and the lower survival in those with positivity for MDM2 suggest a possible association of these proteins with tumor aggressiveness.
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Biomarcadores Tumorais , Neoplasias Ósseas , Condroma , Condrossarcoma , Quinase 4 Dependente de Ciclina , Imuno-Histoquímica , Proteínas Proto-Oncogênicas c-mdm2 , beta Catenina , Humanos , Condrossarcoma/patologia , Condrossarcoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/análise , Masculino , Feminino , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Pessoa de Meia-Idade , beta Catenina/análise , beta Catenina/metabolismo , Adulto , Estudos Retrospectivos , Biomarcadores Tumorais/análise , Prognóstico , Condroma/patologia , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/análise , Idoso , Adulto Jovem , Adolescente , Gradação de Tumores , Criança , Proteínas de Ligação a RNARESUMO
Nephrotoxicity is a common complication that limits the clinical utility of cisplatin. Ferroptosis is an iron-dependent necrotic cell death program that is mediated by phospholipid peroxidation. The molecular mechanisms that disrupt iron homeostasis and lead to ferroptosis are yet to be elucidated. In this study, we aimed to investigate the involvement of nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor that mediates ferroptosis and autophagic degradation of ferritin in nephrotoxicity. Adult male Sprague-Dawley rats were randomly-assigned to four groups: control group, cisplatin (Cis)-treated group, deferiprone (DEF)-treated group, and Cis+DEF co-treated group. Serum, urine, and kidneys were isolated to perform biochemical, morphometric, and immunohistochemical analysis. Iron accumulation was found to predispose to ferroptotic damage of the renal tubular cells. Treatment with deferiprone highlights the role of ferroptosis in nephrotoxicity. Upregulation of NCOA4 in parallel with low ferritin level in renal tissue seems to participate in iron-induced ferroptosis. This study indicated that ferroptosis may participate in cisplatin-induced tubular cell death and nephrotoxicity through iron-mediated lipid peroxidation. Iron dyshomeostasis could be attributed to NCOA4-mediated ferritin degradation.
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Cisplatino , Ferroptose , Coativadores de Receptor Nuclear , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Ferroptose/efeitos dos fármacos , Masculino , Cisplatino/toxicidade , Coativadores de Receptor Nuclear/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Deferiprona/farmacologia , Sistema y+ de Transporte de Aminoácidos/metabolismo , Antineoplásicos , Peroxidação de Lipídeos/efeitos dos fármacos , Ferro/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Ferritinas/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Imuno-HistoquímicaRESUMO
PURPOSE: To histologically quantify the different tissues that make up the porcine ureter, (epithelial, connective, and muscular tissue) in the three segments labelled: cranial, middle and caudal, in order to identify the segment most compatible for use as a vascular graft. METHODS: Fifteen porcine ureters were collected, divided into the three segments, and the samples were stained with hematoxylin and eosin, picrosirius red and Weigert's resorcin-fuchsin. The immunohistochemistry technique was applied for alpha-smooth muscle actin. Collagen fibers, muscle, epithelium, and elastic fibers tissue were quantified, in the entire ureter, and divided into hemispheres, comparing the different segments. RESULTS: When comparing hemisphere segments, significant differences were observed (p < 0.01) for collagen and muscle tissue, with the cranial segment presenting the greatest amount of these components when compared to the middle and caudal. No significant difference was observed between the segments when comparing the entire ureters. CONCLUSIONS: After comparing the segments by hemisphere, the cranial segment presented a slight advantage for use as a vascular graft due to presenting greater collagen fiber content.
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Colágeno , Ureter , Animais , Ureter/anatomia & histologia , Ureter/cirurgia , Suínos , Colágeno/análise , Imuno-Histoquímica , Prótese Vascular , Xenoenxertos , Tecido Elástico/anatomia & histologiaRESUMO
This study presents an observational, cross-sectional analysis of 64 patients diagnosed with small cell lung cancer (SCLC) at a reference laboratory for thoracic pathology between 2022 and 2024. The primary objective was to evaluate the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers such as Chromogranin, and Synaptophysin, utilizing both traditional immunohistochemistry and digital pathology tools. Patients were primarily older adults, with a median age of over 71, and most biopsies were obtained from lung parenchyma. Immunohistochemistry (IHC) was performed using specific monoclonal antibodies, with DLL3 showing variable expression across the samples. Notably, DLL3 was expressed in 72.3% of the cases, with varied intensities and a semi-quantitative H-score applied for more nuanced analysis. ASCL1 was expressed in 97% of cases, with the majority considered low-expressors. Only 11% had high expression. TTF-1, traditionally not a conventional marker for the diagnosis of SCLC, was positive in half of the cases, suggesting its potential as a biomarker. The study underscores the significant variability in the expression of neuroendocrine markers in SCLC, with implications for both diagnosis and potential therapeutic targeting. DLL3, particularly, shows promise as a therapeutic target due to its high expression rate in the cohort. The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches. The findings emphasize the need for further research into the role of these markers in the management and treatment of SCLC, considering the poor prognosis and high mortality rate observed in the cohort.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos , Biomarcadores Tumorais , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Pulmonares , Proteínas de Membrana , Medicina de Precisão , Carcinoma de Pequenas Células do Pulmão , Fatores de Transcrição , Humanos , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Medicina de Precisão/métodos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Idoso de 80 Anos ou mais , Fatores de Transcrição/metabolismo , Estudos Transversais , Imuno-Histoquímica , Proteínas de Ligação a DNA/metabolismo , AdultoRESUMO
INTRODUCTION: Odontogenic keratocyst (OKC) and unicystic ameloblastoma (UA) are lesions of odontogenic origin. Both lesions are morphologically cysts. However, they are classified as developmental cysts and epithelial odontogenic tumours, respectively. Cyclin D1 (CCD1) dysregulation is associated with oncogenic activity and malignancies, while tumour protein p63 (p63) alterations are associated with tumourigenesis. AIM: To evaluate and compare the protein expression of CCD1 and p63 in sporadic OKC (OKC-sp), syndromic OKC (OKC-sy), and UA. MATERIAL AND METHODS: 45 cases from the Anatomical Pathology Department, Faculty of Dentistry, University of Chile were analysed and divided into groups: OKC-sp (n=15), OKC-sy (n=15) and UA (n=15), the latter categorised into intraluminal and/or luminal (n=7) and mural (n=8). Immunohistochemical staining for CCD1 and p63 proteins was performed from paraffin-embedded sections. Statistical analysis included the Shapiro-Wilk test, one-way ANOVA with Tukey's multiple comparisons, and Spearman's correlation coefficient (p<0.05). RESULTS: There was an involvement mainly in women in the mandibular area, and a high frequency of jaw expansion, especially in the mural UA. P63 protein expression was higher than CCD1 in all cystic lesions, particularly in mural UA (p<0.001). No correlation was found between CCD1 and p63 expression. CONCLUSION: P63 may serve as a valuable marker for evaluating cell proliferative activity in odontogenic cystic lesions, providing insights into the aggressive behaviour of mural UA.
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Ameloblastoma , Ciclina D1 , Imuno-Histoquímica , Cistos Odontogênicos , Cistos Odontogênicos/patologia , Humanos , Ameloblastoma/patologia , Ameloblastoma/química , Ameloblastoma/metabolismo , Ciclina D1/análise , Proteínas Supressoras de Tumor/análise , Neoplasias Maxilomandibulares/patologia , Neoplasias Maxilomandibulares/química , Neoplasias Maxilomandibulares/metabolismo , Feminino , Fatores de Transcrição/análise , Masculino , Adulto , Proteínas de Membrana/análise , Adolescente , Biomarcadores Tumorais/análiseRESUMO
BACKGROUND: Queiroz et al. showed that the application of cluster methodology for classifying gastric cancer is suitable and efficient within a Brazilian cohort, which is known for its population heterogeneity. The study highlighted the potential utilization of this method within public health services due to its low-cost, presenting a viable means to improve the diagnosis and prognosis of gastric cancer. BACKGROUND: Our Brazilian cohort with gastric cancer has a distinct distribution between mutated and normal p53. BACKGROUND: New genetic marker-based classifications improve gastric cancer diagnosis accuracy. BACKGROUND: Machine learning integration enhances predictive value in gastric cancer diagnosis. BACKGROUND: Molecular biomarkers complement clinical decisions, advancing personalized medicine. OBJECTIVE: Gastric adenocarcinoma remains an aggressive disease with a poor prognosis, as evidenced by a 5-year survival rate of approximately 31%. The histological classifications already proposed do not accurately reflect the high biological heterogeneity of this neoplasm, particularly in diverse populations, and new classification systems using genetic markers have recently been proposed. Following these newly proposed models, we aimed to assess the cluster distribution in a Brazilian cohort. Furthermore, we evaluated whether the inclusion of other clinical and histological parameters could enhance the predictive value. METHODS: We used a previously described four-immunohistochemistry/EBER-ISH marker to classify a cohort of 30 Brazilian patients with gastric adenocarcinoma into five different clusters and compared the distribution with other genetically diverse populations. Furthermore, we used artificial intelligence methods to evaluate whether other clinical and pathological parameters could improve the results of the methodology. RESULTS: Disclosing the genetic variability between populations, we observed a more balanced distribution of the aberrant/normal p53 ratio (0.6) between patients negative for the other markers tested, unlike previous studies with Asian and North American populations. In addition, decision tree analysis reinforced the efficiency of these new classifications, as the stratification accuracy was not altered with or without additional data. CONCLUSION: Our study underscores the importance of local research in characterizing diverse populations and highlights the complementary role of molecular biomarkers in personalized medicine for gastric adenocarcinoma, enhancing diagnostic accuracy and potentially improving survival rates.
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Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Gástricas , Proteína Supressora de Tumor p53 , Neoplasias Gástricas/genética , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Humanos , Brasil , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/análise , Masculino , Feminino , Adenocarcinoma/genética , Adenocarcinoma/classificação , Adenocarcinoma/patologia , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Estudos de Coortes , Idoso , Análise por Conglomerados , Mutação , Imuno-Histoquímica , Adulto , Prognóstico , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: In the context of postoperative anal pain, understanding the intricate mechanisms and effective interventions is paramount. This study investigates the role of Muscarinic Acetylcholine Receptors (mAChRs) and the IP3-Ca2+-CaM signaling pathway in a rat model of postoperative anal pain, exploring the potential analgesic effects of electroacupuncture. METHODS: Comprehensive approaches involving mechanical sensitivity assays, Western blotting, immunohistochemistry, and intracellular calcium concentration measurement were used. RESULTS: The authors found elevated mAChRs expression in the postoperative pain model. Antagonizing mAChRs reduced pain sensitivity and attenuated the IP3-Ca2+-CaM pathway. Remarkably, electroacupuncture treatment further mitigated pain, potentially by suppressing this signaling cascade. INTERPRETATION: These findings reveal a novel connection between mAChRs and the IP3-Ca2+-CaM pathway in postoperative anal pain and suggest electroacupuncture as a promising avenue for pain relief through these mechanisms, offering insights into innovative strategies for postoperative pain management.
Assuntos
Eletroacupuntura , Hemorroidectomia , Dor Pós-Operatória , Ratos Sprague-Dawley , Receptores Muscarínicos , Transdução de Sinais , Animais , Eletroacupuntura/métodos , Dor Pós-Operatória/terapia , Masculino , Hemorroidectomia/métodos , Receptores Muscarínicos/metabolismo , Pontos de Acupuntura , Canal Anal/cirurgia , Modelos Animais de Doenças , Western Blotting , Ratos , Imuno-Histoquímica , Cálcio/metabolismo , Resultado do TratamentoRESUMO
PURPOSE: Lipopolysaccharides is well-known in the acute renal injury process. It causes widespread activation of inflammatory cascades. Tumor necrosis factor (TNF)-α and interleukin (Il)-6 are essential proinflammatory cytokines that can induce the production of other cytokines in host response. Adalimumab suppresses TNF-α, IL-1ß, and IL-6. We aimed to evaluate whether adalimumab would prevent the toxicity of lipopolysaccharide on the rat renal tissue. METHODS: Adult female Wistar rats were divided into four groups. To the control group, only intraperitoneal saline injection procedure was carried out. For adalimumab group, adalimumab was injected at a dose for two days. For lipopolysaccharide group, animals were injected with lipopolysaccharide (a dose). For lipopolysaccharide-adalimumab group, animals were given adalimumab treatment before the injection of lipopolysaccharide. Histopathological changes and immunohistochemical analysis for TNF-α and IL-6 were determined. RESULTS: The pathological changes and immunohistochemical staining for TNF-α or IL-6 were similar for control and adalimumab groups (p > 0.05). The lipopolysaccharide group had significantly higher distorted features in the renal tissues (p < 0.001), and also significantly prominent immunohistochemical staining for TNF-α or IL-6 (0.003), compared to the control group. No severe pathological feature was detected in the lipopolysaccharide-adalimumab group, but moderate necrosis was found in all cases (p = 0.003). TNF-α staining and IL-6 staining in the lipopolysaccharide group was found to significantly prominent compared to lipopolysaccharide-adalimumab group (p = 0.013). CONCLUSIONS: Because of its anti-inflammatory property, adalimumab pretreatment may have protective effects on experimental kidney injury. Adalimumab could be considered as a protective agent to acute effects of lipopolysaccharide induced renal injury.
Assuntos
Injúria Renal Aguda , Adalimumab , Interleucina-6 , Lipopolissacarídeos , Ratos Wistar , Fator de Necrose Tumoral alfa , Animais , Adalimumab/farmacologia , Adalimumab/uso terapêutico , Feminino , Fator de Necrose Tumoral alfa/análise , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/induzido quimicamente , Interleucina-6/análise , Rim/efeitos dos fármacos , Rim/patologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Imuno-Histoquímica , Ratos , Modelos Animais de Doenças , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: Endometriosis is a disease in which stromal cells and endometrial glands extend outside of the uterine cavity. Nevertheless, treatment failure and recurrence cause difficulties in management. This study aimed to evaluate the receptor-level components of bilateral endometriomas in the recurrence state. METHODS: Our retrospective cohort study was conducted with patients who underwent surgery for bilateral endometriomas between 2015 and 2021. In total, 113 patients were allocated. A total of 76 patients did not meet the eligibility criteria, and the data of 37 patients were evaluated. Medical treatments, recurrences, and postoperative follow-up data were collected. In archived tissue samples, measurements of progesterone receptor A and progesterone receptor B, histoscores and immunoreactivity scores, and their ratios were calculated in the group that received no postoperative medical treatment. Criteria for recurrence were a repeat operation and/or the detection of a new endometrioma>2 cm at the follow-up examination. RESULTS: No recurrence was observed in 73.0% (n=27) of the cases, whereas recurrence was observed in 27.0% (n=10) of the participants. Patients without recurrence had significantly higher progesterone receptor B histoscore/progesterone receptor A histoscore and progesterone receptor B immunoreactivity score/progesterone receptor A immunoreactivity score results (p=0.01). Nevertheless, when the histoscores and immunoreactivity scores for both receptors were contrasted separately, there was no appreciable difference between them. CONCLUSION: The dominance of progesterone receptor B over progesterone receptor A was inversely proportional to the recurrence status in bilateral endometriomas. Furthermore, our study revealed that assessing receptor levels alone did not result in a significant difference in recurrence.
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Endometriose , Receptores de Progesterona , Humanos , Feminino , Endometriose/cirurgia , Endometriose/metabolismo , Endometriose/patologia , Receptores de Progesterona/metabolismo , Receptores de Progesterona/análise , Adulto , Estudos Retrospectivos , Recidiva , Pessoa de Meia-Idade , Imuno-HistoquímicaRESUMO
OBJECTIVES: To assess the effectiveness of ozone therapy in guided bone regeneration (GBR) for critical size calvarial defects in rats. MATERIALS AND METHODS: 96 male Wistar rats were divided into four groups (n = 6 each). An 8 mm critical defect was created in the calvaria of each rat. The groups were: BIO (porcine collagen membrane, BioGide®), BIO + OZ (membrane with systemic ozone therapy every 2 days), COA + OZ (blood clot with ozone therapy), and COA (blood clot only). Evaluations at 7, 15, 30, and 60 days included histological, histomorphometric, inflammatory profile, Micro-CT, and immunohistochemical analyses. Statistical analysis involved two-factor ANOVA with Tukey's post-hoc test for general data, and one-factor ANOVA with Holm-Sidak post-hoc test for Micro-CT data. RESULTS: The BIO + OZ group demonstrated superior bone regeneration with well-organized, mature bone tissue and significant bone formation at 30 and 60 days. The COA + OZ group showed early angiogenesis and reduced inflammation, resulting in complete defect closure by 30 days. The BIO group had good regeneration, but less mature tissue compared to BIO + OZ. The COA group exhibited limited bone formation and higher porosity. CONCLUSION: Ozone therapy positively influences bone regeneration by enhancing cell proliferation and the healing response. CLINICAL RELEVANCE: Improving regenerative processes with auxiliary therapies like ozone therapy can be significant for advancing dental reconstructions.
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Regeneração Óssea , Regeneração Tecidual Guiada , Imuno-Histoquímica , Ozônio , Ratos Wistar , Crânio , Microtomografia por Raio-X , Animais , Ozônio/uso terapêutico , Ratos , Masculino , Regeneração Óssea/efeitos dos fármacos , Regeneração Tecidual Guiada/métodos , Colágeno , Membranas ArtificiaisRESUMO
A mass was removed surgically from the right orbit of a 1-d-old Holstein calf. Grossly, the mass filled the rostral part of an enlarged orbit and compressed the globe toward the caudal pole of the orbit. The brown, 6-cm tumor had central yellow and brown areas, and a smooth, glistening cut surface. Microscopically, the neoplasm was highly cellular and composed of spindle cells arranged in irregular, broad, interlacing streams and bundles, forming a herringbone pattern and supported by a sparse collagenous matrix. Neoplastic cells infiltrated surrounding soft tissues and compressed the globe. The neoplastic cells had positive immunolabeling for α-smooth muscle actin, desmin, and vimentin, and negative immunolabeling for factor VIII, myoglobin, cytokeratin, and skeletal muscle actin. Histopathology and immunohistochemistry results confirmed a diagnosis of leiomyosarcoma. To our knowledge, congenital periocular leiomyosarcoma has not been reported in cattle previously. This rare tumor could be included as a differential diagnosis in newborn calves with periocular masses.
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Doenças dos Bovinos , Leiomiossarcoma , Animais , Bovinos , Leiomiossarcoma/veterinária , Leiomiossarcoma/patologia , Leiomiossarcoma/diagnóstico , Doenças dos Bovinos/patologia , Doenças dos Bovinos/congênito , Doenças dos Bovinos/diagnóstico , Animais Recém-Nascidos , Feminino , Neoplasias Orbitárias/veterinária , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/diagnóstico , Neoplasias Orbitárias/cirurgia , Imuno-Histoquímica/veterináriaRESUMO
The objective of this study was to categorise diseases associated with FeLV infection in cats. A total of 154 cats were submitted to necropsy, histopathology exam and anti-FeLV immunohistochemistry (IHC), and 83 (50.9â¯%) were IHC FeLV-positive. The cats age means of 4.1 years, including 3.6â¯% kittens, 34.9â¯% junior, 37.4â¯% prime, 18.1â¯% mature, 2.4â¯% senior, 3.6â¯% unknown age. Neoplastic diseases were most prevalent with leukaemia and lymphoma being most predominant, followed by viral diseases, bacterial, trauma, degenerative, intoxications, parasitic, malformation and others. FeLV+ cats were 5.73 times more likely to be diagnosed with neoplasms than other diseases. The odds ratio (OR) of FeLV+ cats developing leukaemia (OR = 7.75) and lymphoma (OR = 6.75) was higher than other neoplasms. FeLV infection was more prevalent in the mixed breed, junior to prime, male, with neoplastic diseases, including leukaemia and lymphoma. Therefore, understanding the diseases associated with FeLV is of paramount importance in Brazil due to its high prevalence, and it may encourage the implementation of prophylactic measures to reduce its dissemination.
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Doenças do Gato , Vírus da Leucemia Felina , Leucemia Felina , Gatos , Animais , Vírus da Leucemia Felina/isolamento & purificação , Brasil/epidemiologia , Masculino , Doenças do Gato/virologia , Doenças do Gato/epidemiologia , Feminino , Prevalência , Leucemia Felina/epidemiologia , Leucemia Felina/virologia , Linfoma/epidemiologia , Linfoma/veterinária , Linfoma/virologia , Infecções por Retroviridae/epidemiologia , Infecções por Retroviridae/veterinária , Infecções por Retroviridae/virologia , Imuno-Histoquímica , Neoplasias/epidemiologia , Neoplasias/veterinária , Neoplasias/virologia , Infecções Tumorais por Vírus/veterinária , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologiaRESUMO
Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.
Assuntos
Citocinas , Modelos Animais de Doenças , Ratos Wistar , Receptores de Interleucina-6 , Crânio , Animais , Masculino , Citocinas/metabolismo , Receptores de Interleucina-6/antagonistas & inibidores , Crânio/efeitos dos fármacos , Ratos , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Microtomografia por Raio-X , Peptídeo Hidrolases/metabolismo , Imuno-Histoquímica , Distribuição AleatóriaRESUMO
OBJECTIVE: Tumor budding is a phenomenon in which the tumor cells detach from the main mass and are present at the invasive front. The present study was conducted to study tumor budding in invasive breast carcinoma and to correlate it with clinicopathological parameters and molecular subtypes. METHODS: The study was conducted over a period of 1 year, and tumor budding was studied as a single or group of cells at the invasive front of breast carcinoma counted in a high-power field (40×). The grading was statistically correlated with tumor size, grade, lymph node status, lymphovascular invasion, pathological TNM staging, molecular subtype, and survival of patients. RESULTS: A total of 50 cases of invasive breast carcinoma were included, out of which 66% (n=33) showed high-grade tumor budding, which was statistically significantly higher in grade 2 invasive ductal carcinoma (p<0.05). High tumor budding was associated with lymphovascular invasion, lymph node metastasis, and a high Ki-67 proliferative index. All cases showing low-grade budding were alive until 6 months of diagnosis, but there was no statistically significant association between stage and budding. CONCLUSION: Tumor buds are significantly higher in grade 2 invasive ductal carcinoma with lymphovascular invasion, lymph node metastasis, and a high Ki-67 proliferative index. Immunohistochemistry may prove helpful in distinguishing tumor buds from their mimickers. Further studies with extended follow-up are recommended to predict tumor budding as a prognostic marker in breast carcinoma, which may play an important role in cancer therapy.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Antígeno Ki-67 , Metástase Linfática , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Humanos , Feminino , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Carcinoma Ductal de Mama/patologia , Metástase Linfática/patologia , Adulto , Antígeno Ki-67/análise , Idoso , Imuno-Histoquímica , PrognósticoRESUMO
OBJECTIVE: Placenta accreta spectrum (PAS) is defined as the attachment of the placenta to the uterine wall in varying degrees. However, the studies have explored that the underlying molecular mechanisms of the PAS are very limited. Sirtuins 1 (SIRT1) is associated with placental development by controlling trophoblast cell invasion and remodeling of spiral arteries. We aimed to determine the expression level of SIRT1 in placentas, and maternal and umbilical cord serum of patients with PAS. METHODS: In total, 30 individuals in control, 20 patients in the placenta previa group, and 30 patients in the PAS group were included in this study. The expression levels of SIRT1 in the placentas were determined by Western blot and immunohistochemistry. Serum levels of SIRT1 in maternal and umbilical cord blood were determined by ELISA. RESULTS: SIRT1 was significantly lower in placentas of the PAS. However, maternal and umbilical cord serum samples were not significantly different between groups. CONCLUSION: SIRT1 may play an important role in the pathogenesis of the PAS.
Assuntos
Sangue Fetal , Placenta Acreta , Placenta , Sirtuína 1 , Humanos , Feminino , Gravidez , Sirtuína 1/sangue , Sirtuína 1/análise , Adulto , Placenta/metabolismo , Placenta Acreta/sangue , Placenta Acreta/patologia , Sangue Fetal/metabolismo , Estudos de Casos e Controles , Imuno-Histoquímica , Western Blotting , Ensaio de Imunoadsorção Enzimática , Cordão Umbilical/metabolismo , Cordão Umbilical/patologia , Placenta Prévia/sangueRESUMO
INTRODUCTION: Although nerves and vessels of the penis play important role in erection, there are few studies on their development in human fetus. Therefore, the objective of the present study is to analyze, quantitatively, in the corpora cavernosa and corpus spongiosum, the development of the nerves and vessels in the fetal penis at different gestational ages. MATERIAL AND METHODS: Fifty-six fresh, macroscopically normal human fetuses aged from 13 to 36 weeks post-conception (WPC) were used. Gestational age was determined by the foot length criterion. Penises were immediately fixed in 10% formalin, and routinely processed for paraffin embedding, after which tissue sections from the mid-shaft were obtained. We used immunohistochemical staining to analyze the nerves and vessels in the corpus cavernous and in the corpus spongiosum. These elements were identified and quantified as percentage by using the Image-J software. RESULTS: The quantitative analysis showed that the percentage of nerves varied from 3.03% to 20.35% in the corpora cavernosa and from 1.89% to 23.88% in the corpus spongiosum. The linear regression analysis indicated that nerves growth (incidence) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.9421, p<0.0001) and (r2=0.9312, p<0.0001), respectively, during the whole fetal period studied. Also, the quantitative analysis showed that the percentage of vessels varies from 2.96% to 12.86% in the corpora cavernosa and from 3.62% to 14.85% in the corpus spongiosum. The linear regression analysis indicated that vessels growth (appearance) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.8722, p<0.0001) and (r2=0.8218, p<0.0001), respectively, during the whole fetal period studied. In addition, the linear regression analysis demonstrated a more intense growth rate of nerves in the corpus spongiosum during the 2nd trimester of gestation, when compared with nerves in the corpora cavernosa. In addition, the linear regression analysis demonstrated a more intense growth rate of vessels in the corpus spongiosum when compared with the corpora cavernosa, during the whole fetal period studied. CONCLUSIONS: In the fetal period, the human penis undergoes major developmental changes, notably in the content and distribution of nerves and vessels. We found strong correlation between nerves and vessels growth (amount) with fetal age, both in the corpora cavernosa and corpus spongiosum. There is significant greater proportional number of nerves than vessels during the whole fetal period studied. Also, nerves and vessels grow in a more intense rate than that of the corpora cavernosa and corpus spongiosum areas.
Assuntos
Idade Gestacional , Pênis , Humanos , Masculino , Pênis/irrigação sanguínea , Pênis/embriologia , Pênis/inervação , Feto/irrigação sanguínea , Feto/embriologia , Imuno-Histoquímica , Desenvolvimento Fetal/fisiologiaRESUMO
Background: Primary breast tumors with neuroendocrine (NE) differentiation are a heterogeneous tumor group with diversity of biological behavior, with poorly defined prevalence and prognosis. Objective: To evaluate the chromogranin, synaptophysin, CD56, INSM1 markers expression prevalence and the association between NE differentiation and tumor molecular type. Material and methods: Observational, cross-sectional study which included 110 breast tissue samples with primary invasive carcinoma. Immunohistochemistry was performed for chromogranin, synaptophysin, CD56 and INMS1 markers. NE differentiation was considered with 10-90% positive cells, and NE tumor with > 90% positive cells. Results: 26.3% showed neuroendocrine differentiation. Out of these, 48.2% were luminal-A type, 24.1% luminal-B, 11.5% HER2neu, 17.2% triple-negative; 1.8% were NE tumors. Tumors were marker positive, and out of these to chromogranin in 24.5%, synaptophysin in 28.2%, CD56 in 2.7%, INSM1 in 16.4%. Synaptophysin was expressed in 17.3% luminal-A type, 6.4% luminal-B, 0.9% HER2neu, 3.6% triple-negative. NE differentiation showed association with synaptophysin expression (r = 0.586, p = 0.0001). Conclusion: The NE differentiation prevalence was 26.3% in primary invasive breast cancers, with luminal-A molecular type predominance.
Introducción: los tumores primarios de mama con diferenciación neuroendócrina (NEBC por sus siglas en inglés) son un grupo heterogéneo de tumores con diversidad de comportamiento biológico, con prevalencia y pronóstico poco definido. Objetivo: evaluar la prevalencia de la expresión los marcadores cromogranina, sinaptofisina, CD56, INSM1 y la asociación entre la diferenciación neuroendócrina y el tipo molecular del tumor. Material y métodos: estudio observacional, transversal que incluyó 110 muestras de tejido mamario con carcinoma invasor primario. Se realizó inmunohistoquímica para los marcadores cromogranina, sinaptofisina, CD56 y INMS1. La presencia 10-90% de células positivas se consideró diferenciación neuroendócrina y tumor neuroendócrino con > 90% de células positivas. Resultados: el 26.3% mostró diferenciación neuroendócrina. De estos, 48.2% fueron tipo luminal-A, 24.1% luminal-B, 11.5% HER2neu y 17.2% triple-negativo; 1.8% resultaron tumores neuroendócrinos. Los tumores presentaron marcadores positivos y de estos, 24.5% fueron a cromogranina, 28.2% a sinaptofisina, 2.7% a CD56 y 16.4% a INSM1. La sinaptofisina se expresó en 17.3% del tipo luminal-A, 6.4% luminal-B, 0.9% HER2neu, 3.6% triple-negativo. La diferenciación neuroendócrina mostró asociación con la expresión de sinaptofisina (r = 0.586, p = 0.0001). Conclusión: la prevalencia de la diferenciación neuroendócrina fue del 26.3% en los cánceres invasores primarios de mama, con predominio en el tipo molecular luminal-A.
Assuntos
Biomarcadores Tumorais , Sinaptofisina , Humanos , Feminino , Estudos Transversais , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Adulto , Sinaptofisina/metabolismo , Idoso , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Antígeno CD56/metabolismo , Imuno-Histoquímica , Proteínas Repressoras/metabolismo , Cromograninas/metabolismo , Receptor ErbB-2/metabolismo , Idoso de 80 Anos ou maisRESUMO
The use of tyrosine kinase inhibitors (TKI) has been growing in veterinary oncology and in the past few years several TKI have been tested in dogs. However, different from human medicine, we lack strategies to select patients to be treated with each TKI. Therefore, this study aimed to screen different tumor subtypes regarding TKI target immunoexpression as a predictor strategy to personalize the canine cancer treatment. It included 18 prostatic carcinomas, 36 soft tissue sarcomas, 20 mammary gland tumors, 6 urothelial bladder carcinomas, and 7 tumors from the endocrine system. A total of 87 patients with paraffin blocks were used to perform immunohistochemistry (IHC) of human epidermal growth factor receptor 2 (HER-2), epidermal growth factor receptors 1 (EGFR1), vascular endothelial growth factor receptor 2 (VEGFR-2), platelet derived growth factor receptor beta (PDGFR-ß), c-KIT, and extracellular signal-regulated kinase 1/2 (ERK1/ERK2). The immunohistochemical screening revealed a heterogeneous protein expression among histological types with mesenchymal tumors showing the lowest expression level and carcinomas the highest expression. We have demonstrated by IHC screening that HER2, EGFR1, VEGFR-2, PDGFR-ß and ERK1/ERK2 are commonly overexpressed in dogs with different carcinomas, and KIT expression is considered relatively low in the analyzed samples.