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2.
Cancer Cytopathol ; 132(5): 285-296, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38329321

RESUMEN

BACKGROUND: Neck dissection is a standardized surgical procedure for patients with head and neck squamous cell carcinoma (HNSCC) and plays a critical role in the choice of adjuvant treatment based on histopathological findings. Saline irrigation is routinely performed at the end of surgery. However, this irrigant is not used for diagnostic purposes. METHODS: Intraoperative irrigation of the neck dissection wound was performed in 56 patients with HNSCC (N = 93 neck dissections), and the cytological suspension obtained was processed via the liquid-based cytology (LBC) technique, Papanicolaou staining, and immunocytochemical staining. Microscopic preparations were screened for the presence of tumor cells and classified as positive, borderline, or negative. These results were correlated with the histopathological and clinical data. RESULTS: Neck lavage LBC demonstrated high diagnostic value in detecting lymph node metastases (N+) with extracapsular spread (ECS), with a specificity, sensitivity, negative predictive value, and positive predictive value of 93.1%, 100%, 100%, and 80%, respectively. Tumor cells were detected in 4.8% of N- cases, 20% of N+ cases without ECS, and 100% of N+ cases with ECS. Receiver operating characteristic curve analysis showed an area under the curve of 0.8429 for the prediction of N+ (p < .0001) and 0.9658 for the prediction of N+ with ECS (p < .0001). CONCLUSIONS: Differential lavage cytology can provide valid and rapid information on the lymph node status in patients with HNSCC and showed an excellent correlation with histopathology. Thus, neck lavage LBC may facilitate faster and more reasonable planning of adjuvant treatment and help improve the therapeutic management of patients with HNSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Metástasis Linfática , Disección del Cuello , Irrigación Terapéutica , Humanos , Masculino , Femenino , Proyectos Piloto , Persona de Mediana Edad , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias de Cabeza y Cuello/diagnóstico , Anciano , Metástasis Linfática/patología , Irrigación Terapéutica/métodos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Adulto , Citodiagnóstico/métodos , Anciano de 80 o más Años , Curva ROC , Pronóstico , Valor Predictivo de las Pruebas , Citología
3.
Emerg Infect Dis ; 30(1)2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38146955

RESUMEN

We describe detection of the previously rarely reported gram-positive bacterium Auritidibacter ignavus in 3 cases of chronic ear infections in Germany. In all 3 cases, the patients had refractory otorrhea. Although their additional symptoms varied, all patients had an ear canal stenosis and A. ignavus detected in microbiologic swab specimens. A correct identification of A. ignavus in the clinical microbiology laboratory is hampered by the inability to identify it by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Also, the bacterium might easily be overlooked because of its morphologic similarity to bacterial species of the resident skin flora. We conclude that a high index of suspicion is warranted to identify A. ignavus and that it should be particularly considered in patients with chronic external otitis who do not respond clinically to quinolone ear drop therapy.


Asunto(s)
Micrococcaceae , Otitis Externa , Humanos , Bacterias , Otitis Externa/diagnóstico , Otitis Externa/tratamiento farmacológico , Otitis Externa/microbiología , Conducto Auditivo Externo
4.
Cytopathology ; 35(1): 113-121, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37787092

RESUMEN

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are frequently diagnosed in advanced stages, which limits therapeutic options and results in persistently poor patient outcomes. The aim of this study was to use liquid-based swab cytology (LBC) in combination with dual immunocytochemical detection of migration and proliferation markers Sec62 and Ki67 in order to allow non-invasive early detection of HNSCC as well as to analyse the diagnostic validity of this method for predicting the malignancy of suspicious oral lesions. METHODS: 104 HNSCC patients and 28 control patients, including healthy patients (n = 17), papilloma (n = 1) and leukoplakia patients (n = 10), were included in this study. For all patients, an LBC swab followed by simultaneous immunocytochemical detection of Sec62 and Ki67 was performed. Immunocytochemical as well as cytopathological results were correlated with histological diagnoses and clinical findings. RESULTS: All HNSCC patients (100%) showed dual Sec62/Ki67 positivity, and all control patients except for the papilloma patient were negative for Sec62/Ki67 (96.4%), resulting in a 100% sensitivity and 96.4% specificity of Sec62/Ki67 dual stain for non-invasive detection of HNSCC. The positive predictive value was 99% and the negative predictive value was 100%. Sec62 expression levels showed a positive correlation with tumour de-differentiation (p = 0.0489). CONCLUSION: Simultaneous immunocytochemical detection of Sec62/Ki67 using LBC represents a promising non-invasive and easy-to-apply tool for the early detection of HNSCC in routine clinical practice. This novel technique can help to avoid incisional biopsies and reduce the frequency with which general anaesthesia is used in diagnostic procedures in patients with suspicious oral lesions.


Asunto(s)
Neoplasias de Cabeza y Cuello , Papiloma , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Antígeno Ki-67/metabolismo , Inmunohistoquímica , Neoplasias de Cabeza y Cuello/diagnóstico
5.
Cancer Cell ; 41(8): 1389-1391, 2023 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-37419120

RESUMEN

By comparing indolent/slowly progressing with aggressive/rapidly progressing tumor types, Pandey et al. identify human evidence of immune equilibrium in indolent tumors and immune escape in progressing tumors, suggesting a link between these mechanisms and the epidemiologic phenomenon of overdiagnosis.


Asunto(s)
Neoplasias , Escape del Tumor , Humanos , Neoplasias/inmunología
6.
Int J Mol Sci ; 24(11)2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37298528

RESUMEN

In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter predictive of oncological outcomes (progression-free and overall survival). An approach to the evaluation of predictive markers enabling therapy individualization is the identification of tumor driver genetic mutations. This study was conducted to investigate the role of SEC62, harbored at 3q26 and identified as a driver of breast cancer pathogenesis, in TNBC. We analyzed SEC62 expression in The Cancer Genome Atlas database, and immunohistologically investigated SEC62 expression in pre- and post-NACT tissue samples from 64 patients with TNBC treated at the Department of Gynecology and Obstetrics/Saarland University Hospital/Homburg between January 2010 and December 2018 and compared the effect of SEC62 on tumor cell migration and proliferation in functional assays. SEC62 expression dynamics correlated positively with the response to NACT (p ≤ 0.01) and oncological outcomes (p ≤ 0.01). SEC62 expression stimulated tumor cell migration (p ≤ 0.01). The study findings indicate that SEC62 is overexpressed in TNBC and serves as a predictive marker for the response to NACT, a prognostic marker for oncological outcomes, and a migration-stimulating oncogene in TNBC.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Terapia Neoadyuvante , Oncogenes , Movimiento Celular/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proteínas de Transporte de Membrana/metabolismo
7.
HNO ; 71(7): 446-452, 2023 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-37296331

RESUMEN

At the 2022 annual meetings of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), several studies on radiation therapy for head and neck squamous cell carcinoma (HNSCC) were presented. Among the main topics were new concepts for treatment de-escalation with the goal of reducing side effects. Radiotherapy alone for nasopharyngeal carcinoma with an intermediate-risk profile was found to be noninferior to chemoradiotherapy with cisplatin while improving tolerability. In the phase II DIREKHT trial for adjuvant radiotherapy, individualized deintensification concepts of radiation dose or volume were implemented. Overall, this treatment resulted in excellent levels of locoregional control with a minimal side effects profile. In subgroup analysis, however, an increased locoregional recurrence rate was observed for tumors of the oral cavity. In 2022, as in the previous year, there was a continued focus on the role of immune checkpoint inhibitors in combination with platinum-based chemoradiotherapy in the first-line treatment of locally advanced HNSCC. In the HNSCC-15-132 trial, sequential application of the PD­1 inhibitor pembrolizumab to chemoradiotherapy was not significantly, but numerically superior to concomitant application. The phase III KEYNOTE-412 trial evaluated the efficacy of concomitant and sequential additive pembrolizumab therapy compared to additive placebo in 804 patients with locally advanced HNSCC. The observed benefit in terms of event-free survival in the pembrolizumab group marginally missed statistical significance, probably due to the particular study design. In addition, new 5­year overall survival data from the phase II trial of chemoradiotherapy in combination with the inhibitor of apoptosis proteins (IAP) antagonist xevinapant versus placebo were presented. The xevinapant group continued to demonstrate a significant survival advantage and a sustained response to treatment.


Asunto(s)
Antineoplásicos , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Cisplatino , Oncología Médica
8.
Front Immunol ; 14: 1172768, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37383237

RESUMEN

Background: Due to the expanding role of immune checkpoint inhibition in the treatment of head and neck squamous cell carcinoma, understanding immunological processes in the tumor microevironment (TME) has strong translational importance. Though analytical methods for a comprehensive analysis of the immunological TME have constantly improved and expanded over the past years the prognostic relevance of immune cell composition in head and neck cancer TME largely remains ambiguous with most studies focusing on one or a small subset of immune cells. Methods: The overall survival (OS) of the TCGA-HNSC patient cohort comprising 513 head and neck cancer patients was correlated with a total of 29 different immune metrics including a wide spectrum of immune cell subpopulations as well as immune checkpoint receptors and cytokines using RNAseq based immune deconvolution analyses. The most significant predictors of survival among these 29 immune metrics were validated on a separate HNSCC patient cohort (n=101) using immunohistochemistry: CD3, CD20+CXCR5, CD4+CXCR5, Foxp3 and CD68. Results: Overall immune infiltration irrespective of immune cell composition showed no significant correlation with the patients' overall survival in the TCGA-HNSC cohort. However, when focusing on different immune cell subpopulations, naïve B cells (p=0.0006), follicular T-helper cells (p<0.0001), macrophages (p=0.0042), regulatory T cells (p=0.0306), lymphocytes (p=0.0001), and cytotoxic T cells (p=0.0242) were identified as highly significant predictors of improved patient survival. Using immunohistochemical detection of these immune cells in a second independent validation cohort of 101 HNSCC patients, we confirmed the prognostic relevance of follicular T helper cells, cytotoxic T cells and lymphocytes. In multivariable analysis, HPV negativity and advanced UICC stages were identified as additional prognostic biomarkers associated with poor outcome. Conclusion: Our study highlights the prognostic relevance of the immunological tumor environment in head and neck cancer and demonstrates that a more detailed analysis of immune cell composition and immune cell subtypes is necessary to accurately prognosticate. We observed the highest prognostic relevance for lymphocytes, cytotoxic T cells, and follicular T helper cells, suggesting further investigations focusing on these specific immune cell subpopulations not only as predictors of patient prognosis but also as promising targets of new immunotherapeutic strategies.


Asunto(s)
Neoplasias de Cabeza y Cuello , Linfocitos T Colaboradores-Inductores , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Pronóstico , Linfocitos B
9.
Front Immunol ; 14: 1127576, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37180133

RESUMEN

Introduction: Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common chronic disease with a high impact on patients' quality of life. If conservative and surgical guideline treatment cannot sufficiently control disease burden, biologicals can be considered as a comparably new treatment option that has revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019. With the aim to select patients who benefit from this new treatment and to find a marker for therapy monitoring, we investigated the cellular composition of nasal mucous membranes and inflammatory cells of patients suffering from CRSwNP and undergoing Dupilumab therapy using non-invasive nasal swab cytology. Methods: Twenty CRSwNP patients with the indication for Dupilumab therapy have been included in this prospective clinical study. In total, five study visits were conducted with ambulatory nasal differential cytology using nasal swabs starting with the beginning of therapy and followed by visits every 3 months for 12 months. First, these cytology samples were stained with the May-Grunwald-Giemsa method (MGG) and the percentage of ciliated cells, mucinous cells, eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an immunocytochemical (ICC) ECP-staining was performed to detect eosinophil granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20 questionnaire, olfactometry, the total IgE concentration in peripheral blood as well as the eosinophil cell count in peripheral blood were recorded. The change of parameters was evaluated over one year and the correlation between clinical effectiveness and nasal differential cytology was analyzed. Results: In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant decrease of eosinophils was seen under Dupilumab treatment. When patients were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the percentage eosinophils in nasal swab catology in the first study visit, the Eo-high-group showed a greater change of eosinophils over time (Δ17.82) compared to the Eo-low-group (Δ10.67) but, however, no better response to therapy. The polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral blood showed a significant decrease during the observation period (p<0.0001). Discussion: Nasal swab cytology as an easy-to-apply diagnostic method allows detection and quantification of the different cell populations within the nasal mucosa at a given time. The nasal differential cytology showed a significant decrease of eosinophils during Dupilumab therapy and can therefore be used as non-invasvive method for monitoring therapy success of this cost intensive therapy and potentially can allow an optimized individual therapy planning and management for CRSwNP patients. Since the validity of initial nasal swab eosinophil cell count as a predictive biomarker for therapy response was limited in our study, additional studies including larger number of participants will be necessary to further evaluate the potential benefits for clinical practice of this new diagnostic method.


Asunto(s)
Pólipos Nasales , Rinitis , Sinusitis , Humanos , Pólipos Nasales/diagnóstico , Pólipos Nasales/tratamiento farmacológico , Rinitis/diagnóstico , Rinitis/tratamiento farmacológico , Calidad de Vida , Estudios Prospectivos , Sinusitis/diagnóstico , Sinusitis/tratamiento farmacológico , Mucosa Nasal , Inmunoglobulina E , Enfermedad Crónica
10.
Interv Neuroradiol ; 29(6): 715-724, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35758285

RESUMEN

PURPOSE: Cavernous sinus dural arterio-venous malformations (dAVF) represent a pathologic connection between branches of the internal and/or external carotid artery and the cavernous sinus. Standard endovascular approaches for dAVF treatment are transvenous embolization through the inferior petrosal sinus or the facial vein and transarterial embolization. These approaches are not always successful or feasible, and alternative techniques are required. Here, we present a case series of a minimally invasive transorbital approach with surgical exposure and catheterization of the superior ophthalmic vein for transvenous fistula coiling. METHODS: 14 patients with dAVFs (Barrow Type B to D) that were treated at a tertiary care medical center over a period of 13 years were included in the study. Patients with persisting dAVF associated symptoms were selected for this approach when conventional endovascular interventions were not successful or not feasible. The surgical procedure was performed under general anaesthesia. RESULTS: A successful transorbital approach was performed in all 14 cases. In 12 of 14 patients a catheter assisted successful embolization of the fistula was performed using platinum coils with no relevant residual fistula flow. In two cases, a spontaneous thrombosis of the fistula during the surgical procedure required no further embolization. No postoperative therapy-associated complications were observed. CONCLUSION: The described approach is an effective method to embolize dAVFs in selected cases when catheter assisted transvenous and/or transarterial embolization is not successful or not feasible. In this case series we demonstrate an excellent success rate with no therapy-associated major complications.


Asunto(s)
Anomalías Cardiovasculares , Fístula del Seno Cavernoso de la Carótida , Seno Cavernoso , Malformaciones Vasculares del Sistema Nervioso Central , Embolización Terapéutica , Humanos , Seno Cavernoso/anomalías , Fístula del Seno Cavernoso de la Carótida/terapia , Cateterismo/métodos , Embolización Terapéutica/métodos , Venas , Malformaciones Vasculares del Sistema Nervioso Central/terapia
11.
Cancers (Basel) ; 16(1)2023 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-38201525

RESUMEN

Primary chemoradiotherapy (CRT) is an established treatment option for locally advanced head and neck squamous cell carcinomas (HNSCC) usually combining intensity modified radiotherapy with concurrent platinum-based chemotherapy. Though the majority of patients can be cured with this regimen, treatment response is highly heterogeneous and can hardly be predicted. SEC62 represents a metastasis stimulating oncogene that is frequently overexpressed in various cancer entities and is associated with poor outcome. Its role in HNSCC patients undergoing CRT has not been investigated so far. A total of 127 HNSCC patients treated with primary CRT were included in this study. The median follow-up was 5.4 years. Pretherapeutic tissue samples of the primary tumors were used for immunohistochemistry targeting SEC62. SEC62 expression, clinical and histopathological parameters, as well as patient outcome, were correlated in univariate and multivariate survival analyses. High SEC62 expression correlated with a significantly shorter overall survival (p = 0.015) and advanced lymph node metastases (p = 0.024). Further significant predictors of poor overall and progression-free survival included response to therapy (RECIST1.1), nodal status, distant metastases, tobacco consumption, recurrence of disease, and UICC stage. In a multivariate Cox hazard proportional regression analysis, only SEC62 expression (p = 0.046) and response to therapy (p < 0.0001) maintained statistical significance as independent predictors of the patients' overall survival. This study identified SEC62 as an independent prognostic biomarker in HNSCC patients treated with primary CRT. The role of SEC62 as a potential therapeutic target and its interaction with radiation-induced molecular alterations in head and neck cancer cells should further be investigated.

12.
J Clin Med ; 11(23)2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36498697

RESUMEN

BACKGROUND: Bone-conducted (BC) VEMPs provide important tools for measuring otolith function. However, two major drawbacks of this method are encountered in clinical practice-small n10 amplitude and averaging technique. In this study, we present the results of a new VEMP setup measuring technique combined with a novel single-sweep analysis. METHODS: The study included BC oVEMP data from 92 participants for the evaluation of normative data using a novel analysis technique. For evaluating test-retest reliability, the intraclass correlation coefficient (ICC) was used. RESULTS: We found significant n10 amplitude differences in single-sweep analyses after the first and second measurements. Thereby, mathematical analyses of the head movement did not show any differences in the first or second measurements. The normative n10 amplitude was 20.66 µV with an asymmetric ratio (AR) of 7%. The new value of late shift difference (LSD) was 0.01 ms. The test retest-reliability showed good to excellent ICC results in 9 out of 10 measurements. CONCLUSIONS: Our results support a phenomenon in single-sweep analysis of the first stimuli independent of head movement and signal morphology. Furthermore, the values obtained with the new measurement method appear to be more sensitive and may allow an extended diagnostic range due to the new parameter LSD.

13.
Diagnostics (Basel) ; 12(11)2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36359540

RESUMEN

When we talk about visualization methods in surgery, it is important to mention that the diagnosis of tumors and how we define tumor borders intraoperatively in a correct way are two main things that would not be possible to achieve without this grand variety of visualization methods we have at our disposal nowadays. In addition, histopathology also plays a very important role, and its importance cannot be neglected either. Some biopsy specimens, e.g., frozen sections, are examined by a histopathologist and lead to tumor diagnosis and the definition of its borders. Furthermore, surgical resection is a very important point when it comes to prognosis and life survival. Confocal laser endomicroscopy (CLE) is an imaging technique that provides microscopic information on the tissue in real time. CLE of disorders, such as head, neck and brain tumors, has only recently been suggested to contribute to both immediate tumor characterization and detection. It can be used as an additional tool for surgical biopsies during biopsy or surgical procedures and for inspection of resection margins during surgery. In this review, we analyze the development, implementation, advantages and disadvantages as well as the future directions of this technique in neurosurgical and otorhinolaryngological disciplines.

14.
Front Physiol ; 13: 1014271, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36262254

RESUMEN

The human SEC62 gene is located on chromosome 3q, was characterized as a tumor driver gene and is found to be overexpressed in an ever-growing number of tumors, particularly those with 3q26 amplification. Where analyzed, SEC62 overexpression was associated with poor prognosis. Sec62 protein is a membrane protein of the endoplasmic reticulum (ER) and has functions in endoplasmic reticulum protein import, endoplasmic reticulum-phagy and -in cooperation with the cytosolic protein calmodulin- the maintenance of cellular calcium homeostasis. Various human tumors show SEC62 overexpression in immunohistochemistry and corresponding cell lines confirm this phenomenon in western blots and immunofluorescence. Furthermore, these tumor cells are characterized by increased stress tolerance and migratory as well as invasive potential, three hallmarks of cancer cells. Strikingly, plasmid-driven overexpression of SEC62 in non-SEC62 overexpressing cells introduces the same three hallmarks of cancer into the transfected cells. Depletion of Sec62 from either type of SEC62 overexpressing tumor cells by treatment with SEC62-targeting siRNAs leads to reduced stress tolerance and reduced migratory as well as invasive potential. Where tested, treatment of SEC62 overexpressing tumor cells with the small molecule/calmodulin antagonist trifluoperazine (TFP) phenocopied the effect of SEC62-targeting siRNAs. Recently, first phase II clinical trials with the prodrug mipsagargin/G202, which targets cellular calcium homeostasis in prostate cells as well as neovascular tissue in various tumors were started. According to experiments with tumor cell lines, however, SEC62 overexpressing tumor cells may be less responsive or resistant against such treatment. Therefore, murine tumor models for tumor growth or metastasis were evaluated with respect to their responsiveness to treatment with a mipsagargin analog (thapsigargin), or trifluoperazine, which had previously been in clinical use for the treatment of schizophrenia, or with the combination of both drugs. So far, no additive effect of the two drugs was observed but trifluoperazine had an inhibitory effect on tumor growth and metastatic potential in the models. Here, we review the state of affairs.

15.
Front Physiol ; 13: 880004, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36045752

RESUMEN

Various cancer types including head and neck squamous cell carcinomas (HNSCC) show a frequent amplification of chromosomal region 3q26 that encodes, among others, for the SEC62 gene. Located in the ER membrane, this translocation protein is known to play a critical role as a potential driver oncogene in cancer development. High SEC62 expression levels were observed in various cancer entities and were associated with a poor outcome and increased metastatic burden. Because of its intracellular localization the SEC62 protein is poorly accessible for therapeutic antibodies, therefore a functional SEC62 knockdown represents the most promising mechanism of a potential antineoplastic targeted therapy. By stimulating the Ca2+ efflux from the ER lumen and thereby increasing cellular stress levels, a functional inhibition of SEC62 bears the potential to limit tumor growth and metastasis formation. In this study, two potential anti-metastatic and -proliferative agents that counteract SEC62 function were investigated in functional in vitro assays by utilizing an immortalized human hypopharyngeal cancer cell line as well as a newly established orthotopic murine in vivo model. Additionally, a CRISPR/Cas9 based SEC62 knockout HNSCC cell line was generated and functionally characterized for its relevance in HNSCC cell proliferation and migration as well as sensitivity to SEC62 targeted therapy in vitro.

16.
J Dtsch Dermatol Ges ; 20(9): 1187-1199, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36067526

RESUMEN

The SEC62 gene encodes for a transmembrane protein of the endoplasmic reticulum (ER). Sec62 protein is involved in the post-translational transport of secretory and membrane-bound proteins in eukaryotic cells, regulates intracellular calcium homeostasis through direct interaction with the Sec61 channel and makes a decisive contribution to the cellular compensation of ER stress in the context of recovER-phagy. A significantly increased expression of the SEC62 gene has already been demonstrated in various tumor entities. First approaches of a targeted therapy have been tested for various tumor entities in vitro and in vivo with promising results that motivate further preclinical and clinical studies. Nevertheless, many questions remain unanswered, in particular with regard to the molecular mechanisms underlying the observed clinical effects, and require further investigation in future studies. The protein also plays a relevant role in dermato-oncology. The overexpression of SEC62 in atypical fibroxanthomas and malignant melanomas has already been demonstrated and a correlation of SEC62 expression with various clinical and pathological features has been observed. Future studies, especially in vivo and clinical, will show whether Sec62 can be established as a prognostic marker in dermato-oncology and whether it can serve as a starting point for targeted therapy.


Asunto(s)
Calcio , Retículo Endoplásmico , Calcio/metabolismo , Retículo Endoplásmico/metabolismo , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Procesamiento Proteico-Postraduccional , Transporte de Proteínas/fisiología
17.
Diagnostics (Basel) ; 12(9)2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-36140467

RESUMEN

(1) Background: Computed tomography (CT) is considered mandatory for assessing the extent of pathologies in the paranasal sinuses (PNS) in chronic rhinosinusitis (CRS). However, there are few evidence-based data on the value of ultrasound (US) in CRS. This multicenter approach aimed to compare diagnostic imaging modalities in relation to findings during surgery. (2) Methods: 127 patients with CRS were included in this prospective multicenter study. Patients received preoperative US and CT scans. The sensitivity and specificity of CT and US were extrapolated from intraoperative data. (3) Results: CT scans showed the highest sensitivity (97%) and specificity (67%) in assessing CRS. Sensitivities of B-scan US were significantly lower regarding the maxillary sinus (88%), the ethmoid sinus (53%), and the frontal sinus (45%). The highest overall sensitivity was observed for assessing the pathology of the maxillary sinus. (4) Conclusions: We observed high accuracy with CT, confirming its importance in preoperative imaging in CRS. Despite the high US expertise of all investigators and a standardized examination protocol, the validity of CT was significantly higher than US. Ultrasound of the PNS sinuses is applicable in everyday clinical practice but lacks diagnostic accuracy. Nevertheless, it might serve as a complementary hands-on screening tool to directly correlate the clinical findings in patients with PNS disease.

18.
Diagnostics (Basel) ; 12(9)2022 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-36140522

RESUMEN

Carotid body paragangliomas (CBPs) clinically present as highly vascularized cervical masses with a pathognomonic localization at the carotid artery bifurcation. Following ultrasonography and MRI/CT imaging, surgical resection with optional preoperative embolization is considered as the treatment of choice in most cases. We herein present the case of a 60-year-old female with characteristic clinical signs and imaging findings of a right-sided CBP who finally went to surgical treatment. Intraoperatively, the tumor showed an adherent growth to the hypoglossal nerve that had to be partially resected, resulting in a postoperative nerve palsy. Histological examination of the resected tumor revealed the unexpected diagnosis of a hypoglossal nerve schwannoma. To the best of our knowledge, we herein present the third case reported in the literature of a unilateral hypoglossal schwannoma located at the carotid bifurcation mimicking clinical symptoms, imaging and intraoperative findings of a CBP.

20.
Diagnostics (Basel) ; 12(8)2022 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-36010284

RESUMEN

We present an interesting image of a strikingly intense radioiodine accumulation of a histologically proven pancreatic adenocarcinoma mimicking metastasis of differentiated thyroid cancer in a 63-year-old woman with recurrence of papillary thyroid carcinoma undergoing radioiodine therapy. This interesting image should draw attention to considering pancreatic adenocarcinoma in radioiodine-positive pancreatic lesions.

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