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1.
BMC Womens Health ; 24(1): 265, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678281

RESUMO

BACKGROUND: Enterobius vermicularis (E. vermicularis), also referred to as pinworm, is a widespread human intestinal parasite which predominantly occurs in young children, making their caretakers a population at risk for the transmission of this helminth. It can occasionally affect extraintestinal organs and tissues, including the female genital tract. Infestation can be asymptomatic or manifest as different kinds of gynaecological disorders, such as pelvic inflammation mimicking tumours, abnormal uterine bleeding, or vaginitis. Diagnosis is made by identifying ova in the sample collected from the perineal skin using a transparent adhesive tape or microscopic examination of resected tissue. Mebendazole is the first-line medication and should also be administered to all household members. CASE PRESENTATION: We present a case of a patient who had undergone surgery for invasive cervical cancer with an accidental finding of E. vermicularis eggs in the cervix. CONCLUSIONS: Although not very common, infestation with E. vermicularis should be considered in differential diagnoses of various gynaecological disorders accompanied by histological findings of granulomatous inflammation.


Assuntos
Enterobíase , Enterobius , Neoplasias do Colo do Útero , Humanos , Feminino , Enterobíase/diagnóstico , Enterobíase/complicações , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Enterobius/isolamento & purificação , Animais , Mebendazol/uso terapêutico , Colo do Útero/parasitologia , Colo do Útero/patologia , Diagnóstico Diferencial , Pessoa de Meia-Idade , Adulto
2.
J Pathol ; 258(3): 278-288, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36062412

RESUMO

Morphological features including infiltrative growth, tumour budding (TB), and poorly differentiated clusters (PDCs) have a firmly established negative predictive value in colorectal cancer (CRC). Despite extensive research, the mechanisms underlying different tumour growth patterns remain poorly understood. The aim of this study was to investigate the involvement of epithelial-mesenchymal transition (EMT) in TB and PDCs in CRC. Using laser-capture microdissection, we obtained distinct parts of the primary CRC including TB, PDCs, expansive tumour front, and the central part of the tumour, and analysed the expression of EMT-related markers, i.e. the miR-200 family, ZEB1/2, RND3, and CDH1. In TB, the miR-200 family and CDH1 were significantly downregulated, while ZEB2 was significantly upregulated. In PDCs, miR-141, miR-200c, and CDH1 were significantly downregulated. No significant differences were observed in the expression of any EMT-related markers between the expansive tumour front and the central part of the tumour. Our results suggest that both TB and PDCs are related to partial EMT. Discrete differences in morphology and expression of EMT-related markers between TB and PDCs indicate that they represent different manifestations of partial EMT. TB seems to be closer to complete EMT than PDCs. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , MicroRNAs , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Reino Unido
3.
J Cell Mol Med ; 25(8): 3680-3698, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33650759

RESUMO

Cell lines are widely used for various research purposes including cancer and drug research. Recently, there have been studies that pointed to discrepancies in the literature and usage of cell lines. That is why we have prepared a comprehensive overview of the most common gynaecological cancer cell lines, their literature, a list of currently available cell lines, and new findings compared with the original studies. A literature review was conducted via MEDLINE, PubMed and ScienceDirect for reviews in the last 5 years to identify research and other studies related to gynaecological cancer cell lines. We present an overview of the current literature with reference to the original studies and pointed to certain inconsistencies in the literature. The adherence to culturing rulesets and the international guidelines helps in minimizing replication failure between institutions. Evidence from the latest research suggests that despite certain drawbacks, variations of cancer cell lines can also be useful in regard to a more diverse genomic landscape.


Assuntos
Técnicas de Cultura de Células/métodos , Neoplasias dos Genitais Femininos/patologia , Linhagem Celular Tumoral , Feminino , Humanos
4.
J Surg Res ; 223: 46-57, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29433885

RESUMO

BACKGROUND: The focused sentinel lymph node (SLN) concept we proposed previously relied on real time-quantitative polymerase chain reaction (RT-qPCR) to detect tumor cells, which is too elaborate for intraoperative use. Therefore, we evaluated flow cytometry for intraoperative detection of tumor cells in SLNs. METHODS: Sixty-five consecutive gastric cancer patients were included. SLN analysis was carried out for a single SLN from each patient, using the molecular methods of RT-qPCR (first 30 patients) and flow cytometry (final 35 patients). All LNs underwent hematoxylin and eosin staining and immunohistochemical examination. RESULTS: Extraction of the SLN from a high-risk station was an important determinant for accurate prediction of LN metastases. For RT-qPCR, the sensitivity and specificity of detection were 72.7% and 81.8%, respectively, and for flow cytometry, 36.8% and 100%, respectively. When only high-risk SLNs were analyzed and specimens with <10% viability of leukocytes were excluded, the sensitivity and specificity of flow cytometry were 60% and 100%, respectively. Multivariate analysis identified significant predictors for LN metastases as the molecular method of SLN analysis (P = 0.021; 95% confidence interval [CI]: 1.304-24.284) and lymphovascular invasion (P = 0.002; 95% CI: 2.142-28.555). In subgroup analysis of high-risk SLNs, only RT-qPCR was a significant predictor for LN metastases (P = 0.016; 95% CI: 1.581-91.084). CONCLUSIONS: Flow cytometry of high-risk SLNs, excluding specimens with low cell viability is a rapid, cost-effective, widely obtainable, and highly specific method for SLN metastases detection although it lacks the necessary sensitivity. Therefore, it cannot be recommended as a stand-alone method for the detection of LN metastases during operations.


Assuntos
Citometria de Fluxo/métodos , Linfonodo Sentinela/patologia , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/análise , Antígeno Carcinoembrionário/genética , Molécula de Adesão da Célula Epitelial/análise , Feminino , Humanos , Queratina-20/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade
5.
Radiol Oncol ; 51(2): 151-159, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28740450

RESUMO

BACKGROUND: Colorectal cancer (CRC) represents one of the most common malignancies worldwide. Research has indicated that functional gene changes such as single nucleotide polymorphism (SNP) influence carcinogenesis and metastasis and might have an influence on disease relapse. The aim of our study was to evaluate the role of SNPs in selected genes as prognostic markers in resectable CRC. PATIENTS AND METHODS: In total, 163 consecutive patients treated surgically for CRC of stages I, II and III at the University Medical Centre in Maribor in 2007 and 2008 were investigated. DNA was isolated from formalin-fixed paraffin-embedded CRC tissue from the Department of Pathology and SNPs in genes SDF-1a, MMP7, RAD18 and MACC1 were genotyped using polymerase chain reaction followed by high resolution melting curve analysis or restriction fragment length polymorphism. RESULTS: We found worse disease-free survival (DFS) for patients with TT genotype of SNP rs1990172 in gene MACC1 (p = 0.029). Next, we found worse DFS for patients with GG genotype for SNP rs373572 in gene RAD18 (p = 0.020). Higher frequency of genotype GG of MMP7 SNP rs11568818 was found in patients with T3/T4 stage (p = 0.014), N1/N2 stage (p = 0.041) and with lymphovascular invasion (p = 0.018). For MACC1 rs1990172 SNP we found higher frequency of genotype TT in patients with T3/T4 staging (p = 0.024). Higher frequency of genotype GG of RAD18 rs373572 was also found in patients with T1/T2 stage with disease relapse (p = 0.041). CONCLUSIONS: Our results indicate the role of SNPs as prognostic factors in resectable CRC.

6.
Am J Dermatopathol ; 38(11): 824-831, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27043339

RESUMO

We report 2 cases of primary dermal osteosarcoma. The patients were an 88-year-old man and a 72-year-old man complaining of masses occurring in the ear pavilion and the palm, deemed suspicious for basal cell carcinoma and metastatic colonic carcinoma, and were treated by resection. Microscopically, both featured a dermal lesion mostly composed of atypical spindle cells within a fibrous to hyaline matrix often showing mineralization. Osteoid material was rimmed by atypical tumor cells and was also associated with osteoclast-like giant cells. Tumor cells were positive for SATB2 and negative for markers of epithelial (low-molecular and high-molecular weight cytokeratins, epithelial membrane antigen, p63), melanocytic (S100 protein, HMB45, Melan A), and skeletal/smooth muscle differentiation (desmin, myogenin). No further therapy has been administered. Follow-up at 6 (case 1) and 8 months (case 2) was uneventful. A brief differential diagnosis discussing cutaneous tumors capable of showing osseous differentiation is summarized, along with a review of the pertinent literature. The specificity and sensitivity of SATB2 is also shortly addressed.


Assuntos
Biomarcadores Tumorais/análise , Imuno-Histoquímica , Proteínas de Ligação à Região de Interação com a Matriz/análise , Osteoblastos/química , Osteossarcoma/química , Neoplasias Cutâneas/química , Fatores de Transcrição/análise , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Masculino , Osteoblastos/patologia , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Valor Preditivo dos Testes , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento
8.
Radiol Oncol ; 49(4): 395-401, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26834527

RESUMO

BACKGROUND: Solitary fibrous tumours of the pleura (SFTP) are rare tumours. They are mostly benign. Only around 12% of them are malign ant. In the initial stage they are mostly asymptomatic and by growing they cause chest pain, irritating cough and dyspnoea on account of the pressure created on the surrounding structures. Rare giant tumours have compression symptoms on the mediastinal structures. The condition requires tiered diagnostic radiology. Preoperative biopsy is not successful in most cases. The therapy of choice is radical surgical tumour removal. Malignant or non-radically removed benign solitary fibrous tumours of the pleura additionally require neoadjuvant therapy. CASE REPORT: A 68-year old patient was hospitalized for giant solitary fibrous tumour of the pleura in the right pleural cavity. With its expansive growth the tumour caused the shift of the mediastinum by compressing the lower vena cava, right cardiac auricle as well as the intermediate and lower lobe bronchus. Due to cardiac inflow obstruction and right lung collapse, the patient's life was endangered with signs of cardio-respiratory failure. After preoperative diagnostic radiology, the tumour was surgically removed. Postoperatively, the patient's condition improved. No disease recurrence was diagnosed after a year. CONCLUSIONS: Giant solitary fibrous tumour of the pleura may cause serious and life-threatening conditions by causing compression of the pleural cavity with its expansive growth. Early diagnosis of the condition enables less aggressive as well as video-assisted thoracic surgery in patients with significantly better state of health. Large tumour surgeries in cardio-respiratory affected patients are highly risk-associated procedures.

9.
Radiol Oncol ; 49(3): 256-64, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26401131

RESUMO

BACKGROUND: Helicobacter pylori infection is the main cause of gastric cancer. The disease progression is influenced by the host inflammatory responses, and cytokine single nucleotide polymorphisms (SNPs) may have a role in the course of the disease. The aim of our study was to investigate proinflammatory cytokine polymorphisms, previously associated with the development of gastric cancer, in a Slovenian population. PATIENTS AND METHODS: In total 318 patients and controls were selected for the study and divided into three groups: (i) patients with gastric cancer (n = 58), (ii) patients with chronic gastritis (n = 60) and (iii) healthy control group (n = 200). H. pylori infection in patient groups was determined by serology, histology and culture. Four proinflammatory gene polymorphisms were determined (IL-1ß, IL-1ra, TNF-α, TLR-4) in all subjects. RESULTS: We found a statistically significant difference between males and females for the groups (p = 0.025). Odds ratio (OR) for gastric cancer risk for females was 0.557 (95% confidence interval [CI]: 0.233-1.329) and for chronic gastritis 2.073 (95% CI: 1.005-4.277). IL-1B-511*T/T homozygous allele for cancer group had OR = 2.349 (95% CI: 0.583-9.462), heterozygous IL-1B-511*T had OR = 1.470 (95% CI: 0.583-3.709) and heterozygotes in TNF-A-308 genotype for chronic gastritis had OR = 1.402 (95% CI: 0.626-3.139). Other alleles had OR less than 1. CONCLUSIONS: We could not prove association between gastric cancer and chronic gastritis due to H. pylori in any cytokine SNPs studied in Slovenian population. Other SNPs might be responsible besides infection with H. pylori for the progression from atrophy to neoplastic transformation.

10.
Radiol Oncol ; 49(4): 357-64, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26834522

RESUMO

BACKGROUND: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. PATIENTS AND METHODS: 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman's rank correlation, Mann Whitney U test and χ(2) test for statistical analysis. RESULTS: Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). CONCLUSIONS: Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated.

11.
HPB (Oxford) ; 16(3): 235-42, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23509992

RESUMO

OBJECTIVES: The aim of this study was to assess whether biological markers can provide prognostic information additional to that supplied by the clinical risk score (CRS) in patients with colorectal liver metastases. METHODS: A retrospective review of a prospectively maintained database was conducted. Patients selected for this study were treated between 1996 and 2011 with potentially curative liver surgery. Expressions of p53, Ki-67 and thymidylate synthase were assayed using immunohistochemical techniques on tissue microarrays. RESULTS: A total of 98 (24%) of 406 patients met the inclusion criteria. The median follow-up was 103 months. Analysis revealed a correlation between p53 protein overexpression and high CRS (P = 0.058). Following multivariate analysis, only high CRS remained as an independent negative prognostic predictor of survival (P = 0.018), as well as an indicator of early recurrence of disease (P = 0.010). Of the biological markers investigated, only Ki-67 overexpression was identified as a positive predictor of survival on multivariate analysis (P = 0.038). CONCLUSIONS: Ki-67 overexpression was a positive predictor of survival. Only high CRS remained an independent negative prognostic predictor.


Assuntos
Neoplasias Colorretais/patologia , Técnicas de Apoio para a Decisão , Hepatectomia , Antígeno Ki-67/análise , Neoplasias Hepáticas , Timidilato Sintase/análise , Proteína Supressora de Tumor p53/análise , Adulto , Idoso , Distribuição de Qui-Quadrado , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Análise Serial de Tecidos , Resultado do Tratamento
12.
Cancers (Basel) ; 16(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38610950

RESUMO

(1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p = 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p = 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.

13.
J Ovarian Res ; 15(1): 73, 2022 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35718769

RESUMO

High grade epithelial ovarian cancer (EOC) represents a diagnostic and therapeutic challenge due to its aggressive features and short recurrence free survival (RFS) after primary treatment. Novel targets to inform our understanding of the EOC carcinogenesis in the translational machinery can provide us with independent prognostic markers and provide drugable targets. We have identified candidate eukaryotic initiation factors (eIF) and eukaryotic elongation factors (eEF) in the translational machinery for differential expression in EOC through in-silico analysis. We present the analysis of 150 ovarian tissue microarray (TMA) samples on the expression of the translational markers eIF2α, eIF2G, eIF5 (eIF5A and eIF5B), eIF6 and eEF1A1. All translational markers were differentially expressed among non-neoplastic ovarian samples and tumour samples (borderline tumours and EOC). In EOC, expression of eIF5A was found to be significantly correlated with recurrence free survival (RFS) and expression of eIF2G and eEF1A1 with overall survival (OS). Expression correlation among factor subunits showed that the correlation of eEF1A1, eIF2G, EIF2α and eIF5A were significantly interconnected. eIF5A was also correlated with eIF5B and eIF6. Our study demonstrates that EOCs have different translational profile compared to benign ovarian tissue and that eIF5A is a central dysregulated factor of the translation machinery.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/patologia , Fatores de Alongamento de Peptídeos/metabolismo , Prognóstico
14.
Clin Case Rep ; 9(6): e04355, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34429970

RESUMO

Despite mostly indolent course and favorable postoperative outcome long-term follow-up studies are needed to identify the most appropriate therapeutic strategies to minimize surgical morbidity and neurologic injury in patients with RGNT.

15.
Folia Neuropathol ; 59(2): 205-211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34284548

RESUMO

Light-chain deposition disease (LCDD), a rare type of monoclonal immunoglobulin deposition disease, can be presented as systemic or localized, very rarely affecting central nervous system (CNS). Only 10 cases of CNS-LCDD have been described so far. We present an eleventh case of cerebral tumour-like LCDD, called aggregoma, and compare it with previously reported cases. A 49-year-old patient was admitted to the hospital due to a first generalized epileptic seizure. Magnetic resonance imaging (MRI) showed focal lesion in the right occipital lobe. Abundant parenchymal aggregates of pale eosinophilic material were observed, Congo red negative, Thioflavin T moderately positive, and l-light chain positive, but k negative in immunofluorescence with mild perivascular lymphoplasmacytic infiltrates in the intervening brain tissue. Clonality testing by next-generation sequencing showed the monoclonal nature of B-lymphocytes. Electron microscopy showed a finely granular ultrastructure of the aggregates without deposition in the vessel walls. A whole-body workup did not show any extra-cerebral immune dyscrasias.


Assuntos
Encéfalo , Cadeias Leves de Imunoglobulina , Encéfalo/metabolismo , Proliferação de Células , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cadeias Leves de Imunoglobulina/metabolismo , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade
16.
Cells ; 11(1)2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-35011679

RESUMO

Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for approximately 15-20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and performed a detailed morphological and molecular characterisation and a comprehensive comparison with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence microscopy were used for morphological studies; immunocytochemical staining for hormone receptor, p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUM-BrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile; quantifiable morphological properties; and genetic stability up to (at least) the 6th passage.


Assuntos
Neoplasias de Mama Triplo Negativas/genética , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Transdução de Sinais
17.
Materials (Basel) ; 14(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205030

RESUMO

The metallic-associated adverse local tissue reactions (ALTR) and events accompanying worn-broken implant materials are still poorly understood on the subcellular and molecular level. Current immunohistochemical techniques lack spatial resolution and chemical sensitivity to investigate causal relations between material and biological response on submicron and even nanoscale. In our study, new insights of titanium alloy debris-tissue interaction were revealed by the implementation of label-free high-resolution correlative microscopy approaches. We have successfully characterized its chemical and biological impact on the periprosthetic tissue obtained at revision surgery of a fractured titanium-alloy modular neck of a patient with hip osteoarthritis. We applied a combination of photon, electron and ion beam micro-spectroscopy techniques, including hybrid optical fluorescence and reflectance micro-spectroscopy, scanning electron microscopy (SEM), Energy-dispersive X-ray Spectroscopy (EDS), helium ion microscopy (HIM) and micro-particle-induced X-ray emission (micro-PIXE). Micron-sized wear debris were found as the main cause of the tissue oxidative stress exhibited through lipopigments accumulation in the nearby lysosome. This may explain the indications of chronic inflammation from prior histologic examination. Furthermore, insights on extensive fretting and corrosion of the debris on nm scale and a quantitative measure of significant Al and V release into the tissue together with hydroxyapatite-like layer formation particularly bound to the regions with the highest Al content were revealed. The functional and structural information obtained at molecular and subcellular level contributes to a better understanding of the macroscopic inflammatory processes observed in the tissue level. The established label-free correlative microscopy approach can efficiently be adopted to study any other clinical cases related to ALTR.

18.
Radiol Oncol ; 56(1): 76-82, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34529911

RESUMO

BACKGROUND: The aim of this study was to evaluate changes in prognostic risk profiles of women with endometrial cancer by comparing the clinical risk assessment with the integrated molecular risk assessment profiling. PATIENTS AND METHODS: This prospective study recruited patients with biopsy proven endometrial cancer treated at the University Medical Centre Maribor between January 2020 to February 2021. Patient clinical data was assessed and categorized according to the currently valid European Society of Gynaecological Oncology, European SocieTy for Radiotherapy and Oncology, and European Society of Pathology (ESGO/ESTRO/ESP) guidelines on endometrial cancer. Molecular tumour characterization included determination of exonuclease domain of DNA polymerase-epsilon (POLE) mutational status by Sanger sequencing and imunohistochemical specimen evaluation on the presence of mismatch repair deficiencies (MMRd) and p53 abnormalities (p53abn). RESULTS: Fourty-five women were included in the study. Twenty-two tumours were of non-specific mutational profile (NSMP) (56.4%), 13 were classified as MMRd (33.3%), 3 were classified as p53abn (7.7%) and 1 was classified as POLE mutated (2.6%). Six tumours (15.4%) had multiple molecular classifiers, these were studied separately and were not included in the risk assessment. The clinical risk-assessment classified 21 women (53.8%) as low-risk, 5 women (12.8%) as intermediate risk, 2 women as high-intermediate risk (5.1%), 10 women (25.6%) as high risk and 1 patient as advanced metastatic (2.6%). The integrated molecular classification changed risk for 4 women (10.3%). CONCLUSIONS: Integrated molecular risk improves personalized risk assessment in endometrial cancer and could potentially improve therapeutic precision. Further molecular stratification with biomarkers is especially needed in the NSMP group to improve personalized risk-assessment.


Assuntos
Neoplasias do Endométrio , DNA Polimerase II/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Prognóstico , Estudos Prospectivos , Medição de Risco
19.
J Clin Med ; 10(24)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34945073

RESUMO

(1) Background: There are limited data on the success of conservative treatment of high-grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of treatment with LLETZ. (2) Methods: Patients aged 18-40 with histological HSIL (with high-grade cervical intraepithelial neoplasia, CIN2p16+ and CIN3), were randomly assigned to treatment with imiquimod or LLETZ. The primary outcome was defined as the absence of HSIL after either treatment modality. The secondary outcomes were the occurrence of side effects. (3) Results: 52 patients were allocated in each group and were similar regarding baseline characteristics. In the imiquimod group, 82.7% of patients completed treatment, which was successful in 51.9%. All patients in the LLETZ group completed treatment, which was successful in 92.3% (p < 0.001). In the subgroup of CIN2p16+ patients, treatment with imiquimod was not inferior to LLETZ (73.9% vs. 84.2%, p = 0.477). During and after treatment, no cases of progression to cancer were observed. Side effects and severe side effects (local and systemic) were more prevalent in the imiquimod than in the LLETZ group (88.5% vs. 44.2% (p-value < 0.001) and 51.9% vs. 13.5% (p-value < 0.001), respectively). (4) Conclusion: Generally, in patients with HSIL, LLETZ remains the gold standard of treatment. However, in a subgroup analysis of patients with CIN2p16+, the success rate was comparable between the two treatment modalities. Due to the prevalence of side effects, the treatment compliance with imiquimod use may, however, present a clinically important issue.

20.
Acta Dermatovenerol Alp Pannonica Adriat ; 29(4): 215-218, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33348942

RESUMO

We present a case report of a 64-year-old female patient with a 5-year history of a digital papule that clinically mimicked a common wart but was histologically diagnosed as digital squamous cell carcinoma (DSCC), a rare malignant cutaneous entity etiologically associated with high-risk human papillomaviruses (HR HPVs). This DSCC was positive for HPV73, which is currently classified under possible human carcinogens and has already been identified in DSCCs. Treatment with electrocoagulation and subsequent total excision with safety margins was successful, and no recurrence was detected during 6 years of follow-up. Analogously to cervical and other anogenital carcinomas, we assume that the incidence of DSCC will significantly decrease in the near future due to the widespread use of effective prophylactic HPV vaccines, which cover the majority of HR HPV types also associated with DSCC. However, HPV73 and other possibly carcinogenic and HR HPV types (as classified per the International Agency for Research on Cancer), which are not included in current prophylactic measures, will cause some portion of HPV-associated neoplasms, but this portion will be very minor.


Assuntos
Alphapapillomavirus/isolamento & purificação , Carcinoma de Células Escamosas/virologia , Neoplasias Cutâneas/terapia , Verrugas/virologia , Carcinoma de Células Escamosas/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Pele/virologia , Neoplasias Cutâneas/virologia , Verrugas/terapia
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