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AIMS AND OBJECTIVES: Because of its rarity, limited data concerning brain metastasis (BM) from bladder cancer (BCa) are available, so this phenomenon remains unclear. We aimed to contribute to understanding this unique patient population's clinical behavior and outcomes. METHODS/MATERIALS: This retrospective cohort study included 27 BCa patients with BM treated at our Cancer Institute between April 2009 and December 2022. The time from initial diagnosis to BM and overall survival from BM diagnosis were calculated (Kaplan-Meier method). Cox regression was used to test key clinicopathologic associations. RESULTS: A total of 27 patients were included in the study (male/female = 23/4). The median patient age at BM diagnosis was 62.0 (47-79) years. The median interval from initial diagnosis to BM was 11.0 ± 2.59 (95 % CI, 5.91-16.08) months. Twenty (74.0 %) patients were diagnosed with BM by postsymptomatic imaging. The most common symptoms were headache-dizziness (n = 9, 33.3 %), seizure (n = 3, 11.1 %), hemiparesis (n = 2, 7.4 %), and vision defects (n = 2, 7.4 %). The most common sites of extracranial metastasis were the lung (n = 10, 52.6 %), bone (n = 7, 36.8 %), and lymph nodes (n = 6, 31.5 %). More than half of the patients (55.5 %) had multiple BMs. Eight (29.6 %) patients underwent surgery for BM. All of the patients received radiotherapy (RT) for BM (whole-brain radiotherapy (WBRT)/stereotactic radiotherapy (SRT) = 24/3), and eight patients received RT for the second time. Six patients were treated with systemic chemotherapy (CT) after BM. The median survival from BM was 3.0 ± 1.2 (95 % Cl, 0.4-5.5) months in the entire cohort. A low number of BMs (HR 0.270, 95 % CI 0.083-0.885; p = 0.031), surgery for BM (HR 0.174, 95 % CI 0.043-0.712; p = 0.015), CT after BM (HR 0.207, 95 % CI 0.057-0.755; p = 0.017), and better ECOG performance score (HR 0.248, 95 % CI 0.074-0.836; p = 0.025) were associated with better OS. CONCLUSIONS: Factors associated with improved survival in BCa patients with BM include a few brain lesions, intracranial resection, CT after BM, and better ECOG performance scores. Larger-scale prospective studies are needed to define the optimal management strategy further.
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Neoplasias Encefálicas , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/terapia , Femenino , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/terapia , Anciano , Estudios Retrospectivos , PronósticoRESUMEN
AIMS AND OBJECTIVES: Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is a new entity considered a biologically distinct subtype from HER2-zero BC. However, the importance of HER2 low expression on the activity of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) remains unclear. METHODS/MATERIALS: We conducted a single-center retrospective study including hormone receptor-positive (HR +) /HER2- metastatic BC (mBC) patients treated with CDK4/6i plus endocrine treatment (ET) as first-line therapy. Clinical outcomes were analyzed according to HER2 expression. RESULTS: 258 women were analyzed with a median follow-up of 25.4 months; 39.9% had HER2 low, and 60.1% had HER2 zero BC. Median progression-free survival (mPFS) in the HER2-low group was 27.6 months compared with 44.3 months in the HER2-zero group (p = 0.341). In patients receiving ribociclib, the mPFS in the HER2-low group was 24.2 months compared with 53.1 months in the HER2-zero group (multivariate-adjusted HR: 1.981, 95 Cl 1.094-3.586; p = 0.024). The survival probabilities at 24, 36 and 48 months for the HER2 low and HER2 zero groups were 82%, 69%, 69% and 83%, 75% and 69%, respectively (p = 0.336). Objective response rate (p = 0.179) and disease control rate (p = 0.338) did not significantly differ between HER-2-low and HER-2-zero groups. CONCLUSIONS: The mPFS in the Her2-zero group was almost twice that of the Her2-low group, but the difference was not statistically significant. mPFS was significantly longer in the HER2-zero group compared to the HER2-low group in patients receiving ribociclib. More prospective studies are needed to understand the actual consequences of this biomarker.
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Aminopiridinas , Neoplasias de la Mama , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Inhibidores de Proteínas Quinasas , Purinas , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Estudios Retrospectivos , Anciano , Adulto , Inhibidores de Proteínas Quinasas/uso terapéutico , Purinas/uso terapéutico , Aminopiridinas/uso terapéutico , Supervivencia sin Progresión , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic ß cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients' own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward âthe implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance.
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Anal fissure is common and painful disease of anorectum. In this study, microparticles containing nifedipine and lidocaine HCl were prepared by spray drying and applied to bio-degradable and bio-stable tampons. Characterization of microparticles was determined by visual analyses, mass yield, particle size measurement, encapsulation efficiency, drug loading and in vitro drug release. Mass yield was between 5.5 and 45.9%. The particle size was between 15.1 and 26.8 µm. Encapsulation efficiency were 96.142 ± 5.931 and 85.571 ± 3.301; drug loading were 65.261 ± 3.914% and 37.844 ± 4.339% of L2 and N1, respectively. Well-separated, mainly spherical microparticles with suitable properties were obtained. Optimum microparticles were applied to tampons. Physical properties and visual characteristics of tampons were investigated before and after binder application. In vitro drug release from tampons were also examined. According to the results, textile-based carrier systems loaded microparticles containing nifedipine and lidocaine HCl will be an effective and promising alternative for current anal fissure treatment.
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Anestésicos Locales/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Fisura Anal/tratamiento farmacológico , Lidocaína/administración & dosificación , Nifedipino/administración & dosificación , Tampones Quirúrgicos , Vasodilatadores/administración & dosificación , Alginatos/química , Anestésicos Locales/farmacocinética , Portadores de Fármacos/química , Liberación de Fármacos , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Humanos , Lidocaína/farmacocinética , Nifedipino/farmacocinética , Textiles/análisis , Vasodilatadores/farmacocinéticaRESUMEN
The relationship between cell viability and adhesion behavior, and micro-deformation mechanisms was investigated on austenitic 316L stainless steel samples, which were subjected to different amounts of plastic strains (5%, 15%, 25%, 35% and 60%) to promote a variety in the slip and twin activities in the microstructure. Confocal laser scanning microscopy (CLSM) and field emission scanning electron microscopy (FESEM) revealed that cells most favored the samples with the largest plastic deformation, such that they spread more and formed significant filopodial extensions. Specifically, brain tumor cells seeded on the 35% deformed samples exhibited the best adhesion performance, where a significant slip activity was prevalent, accompanied by considerable slip-twin interactions. Furthermore, maximum viability was exhibited by the cells seeded on the 60% deformed samples, which were particularly designed in a specific geometry that could endure greater strain values. Overall, the current findings open a new venue for the production of metallic implants with enhanced biocompatibility, such that the adhesion and viability of the cells surrounding an implant can be optimized by tailoring the surface relief of the material, which is dictated by the micro-deformation mechanism activities facilitated by plastic deformation imposed by machining.
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Adhesión Celular , Supervivencia Celular , Prótesis e Implantes , Acero Inoxidable , Línea Celular , Humanos , Microscopía Electrónica de Rastreo , SeudópodosRESUMEN
Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically in tumor cells and its efficacy has been tested in pre-clinical models by delivering it systemically as a purified ligand or via engineered stem cells (SC). However, about 50% of tumor lines are resistant to TRAIL and overcoming TRAIL resistance in aggressive tumors, such as glioblastoma-multiforme (GBM), and understanding the molecular dynamics of TRAIL-based combination therapies are critical to broadly use TRAIL as a therapeutic agent. In this study, we developed death receptor (DR)4/5-reporters that offer an imaging-based platform to identify agents that act in concert with a potent, secretable variant of TRAIL (S-TRAIL) by monitoring changes in DR4/5 expression. Utilizing these reporters, we show a differential regulation of DR4/5 when exposed to a panel of clinically relevant agents. A histone deacetylase inhibitor, MS-275, resulted in upregulation of DR4/5 in all GBM cell lines, and these changes could be followed in real time both in vitro and in vivo in mice bearing tumors and they correlated with increased TRAIL sensitivity. To further assess the dynamics of combinatorial strategies that overcome resistance of tumors to SC released S-TRAIL, we also engineered tumor cells to express live-cell caspase-reporters and SCs to express S-TRAIL. Utilizing DR4/5 and caspase reporters in parallel, we show that MS-275 sensitizes TRAIL-resistant GBM cells to stem cell (SC) delivered S-TRAIL by changing the time-to-death in vitro and in vivo. This study demonstrates the effectiveness of a combination of real-time reporters of TRAIL-induced apoptosis pathway in evaluating the efficacy of SC-TRAIL-based therapeutics and may have implications in targeting a broad range of cancers.
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Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Animales , Antineoplásicos/metabolismo , Apoptosis , Benzamidas/farmacología , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Femenino , Glioblastoma , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Ratones , Ratones Desnudos , Microscopía Fluorescente , Células-Madre Neurales/metabolismo , Células-Madre Neurales/trasplante , Piridinas/farmacología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Imagen de Lapso de Tiempo , Células Tumorales Cultivadas , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Approximately 20% of tumors contain activating mutations in the RAS family of oncogenes. As tumors progress to higher grades of malignancy, the expression of oncogenic RAS has been reported to increase, leading to an oncogene-induced senescence (OIS) response. Evasion of this senescence barrier is a hallmark of advanced tumors indicating that OIS serves a critical tumor-suppressive function. Induction of OIS has been attributed to either RAS-mediated production of reactive oxygen species (ROS) or to induction of a DNA damage response (DDR). However, functional links between these two processes in triggering the senescent phenotype have not been explicitly described. Our previous work has shown that, in cultured untransformed cells, preventing elimination of oxidized guanine deoxyribonucleotides, which was achieved by suppressing expression of the cellular 8-oxo-dGTPase, human MutT homolog 1 (MTH1), sufficed to induce a DDR as well as premature senescence. Here, we demonstrate that overexpression of MTH1 can prevent the oncogenic H-RAS-induced DDR and attendant premature senescence, although it does not affect the observed elevation in ROS levels produced by RAS oncoprotein expression. Conversely, we find that loss of MTH1 preferentially induces an in vitro proliferation defect in tumorigenic cells overexpressing oncogenic RAS. These results indicate that the guanine nucleotide pool is a critical target for intracellular ROS produced by oncogenic RAS and that RAS-transformed cells require robust MTH1 expression to proliferate.
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Daño del ADN/genética , Enzimas Reparadoras del ADN/biosíntesis , Genes ras , Nucleótidos de Guanina/metabolismo , Monoéster Fosfórico Hidrolasas/biosíntesis , Línea Celular , Proliferación Celular , Senescencia Celular/genética , Humanos , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismoAsunto(s)
Suero Antilinfocítico/efectos adversos , Pérdida Auditiva Súbita/inducido químicamente , Linfocitos T/inmunología , Adulto , Suero Antilinfocítico/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Humanos , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , MasculinoRESUMEN
In this study of 22 patients with laryngeal cancer, computed tomographic (CT) scans in the axial plane were compared with histopathological sections prepared in the same plane. The value of the preoperative CT for evaluating tumor invasion, location and size was then investigated. Findings demonstrated that CT was most sensitive in determining tumor invasion to the paralaryngeal and preepiglottic spaces, anterior and posterior commissures and subglottis. In contrast, CT was less sensitive in determining actual tumor invasion to the laryngeal cartilages, extralaryngeal tissues and metastases to cervical lymph nodes.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/patología , Tomografía Computarizada por Rayos X , Carcinoma de Células Escamosas/cirugía , Técnica de Descalcificación , Epiglotis/diagnóstico por imagen , Epiglotis/patología , Reacciones Falso Positivas , Femenino , Glotis/diagnóstico por imagen , Glotis/patología , Humanos , Cartílagos Laríngeos/diagnóstico por imagen , Cartílagos Laríngeos/patología , Neoplasias Laríngeas/cirugía , Laringectomía , Laringoscopía , Laringe/diagnóstico por imagen , Laringe/patología , Metástasis Linfática , Masculino , Micromanipulación , Persona de Mediana Edad , Cuello , Invasividad Neoplásica , Estadificación de Neoplasias , Cuidados Preoperatorios , Sensibilidad y EspecificidadRESUMEN
A solitary fibrous tumour is a pleural tumour which may rarely be detected at non-pleural sites. In this report, the case of a solitary fibrous tumour arising from the sublingual salivary gland is described.
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Mesotelioma/patología , Neoplasias de la Glándula Sublingual/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Fine needle aspiration cytologic findings in two cases of malignant lymphoepithelial lesion (MLEL) of the parotid glands are presented. Aspirates of both cases showed individual or cohesive clusters of tumor cells intermingling with mature lymphocytes. Cervical lymph node aspirates in both cases were similar to those seen in the parotids. Our findings suggest that neither cytology nor histology of the cervical lymph nodes is conclusive in establishing the primary site of a metastatic lymphoepitheliomalike carcinoma. MLEL of the salivary glands must be included in the differential diagnosis.
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Carcinoma de Células Escamosas/patología , Neoplasias de las Glándulas Salivales/patología , Adulto , Biopsia con Aguja , Carcinoma de Células Escamosas/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Ganglios Linfáticos/patología , Persona de Mediana Edad , Neoplasias de las Glándulas Salivales/diagnósticoAsunto(s)
Antibacterianos/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Erupciones por Medicamentos/etiología , Otitis Externa/tratamiento farmacológico , Adulto , Anciano , Dermatitis Alérgica por Contacto/diagnóstico , Erupciones por Medicamentos/diagnóstico , Dermatosis Facial/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A rare undifferentiated carcinoma with lymphoid stroma (UCLS) of the parotid gland is described in a white Turkish patient. The raised serum IgG to Epstein-Barr virus capsid antigen suggests a causal relationship between Epstein-Barr virus and this type of salivary gland carcinoma. Some clinical features are briefly reviewed.
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Carcinoma/patología , Neoplasias de la Parótida/patología , Carcinoma/microbiología , Femenino , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4 , Humanos , Persona de Mediana Edad , Neoplasias de la Parótida/microbiología , Infecciones Tumorales por Virus/complicacionesRESUMEN
Fine needle aspiration cytology of oral cavity and jaw bone lesions was performed on 102 patients. The cytologic diagnoses were compared with the results of histologic examination. Thirteen of the 15 histologically malignant lesions and 71 of the 87 histologically benign lesions were cytologically diagnosed accurately. In 12 (92%) of the malignant and 69 (97%) of the benign lesions, specific cytologic diagnoses were given that proved the same or very similar to the final histologic diagnoses. This study showed that the overall accuracy of fine needle aspiration cytology in the oral cavity and jaw bones is high and is not significantly different from that obtained in other body regions.
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Carcinoma de Células Escamosas/patología , Neoplasias Maxilomandibulares/patología , Maxilares/patología , Neoplasias de la Boca/patología , Boca/patología , Quistes Odontogénicos/patología , Biopsia con Aguja , Errores Diagnósticos , Técnicas Histológicas , Humanos , Inflamación/patologíaRESUMEN
Aspiration cytologic findings in a case of benign lymphoepithelial lesion (BLL) of the parotid gland are presented. The aspirate contained a polymorphous lymphoid population, histiocytes, myoepithelial and ductal epithelial cells and numerous bluish, calcified bodies. A cytologic diagnosis of benign nonneoplastic lesion, consistent with chronic sialadenitis and microlithiasis, was made. The clinical impression of neoplasia was inconsistent with the cytologic findings. Subsequent histologic examination showed classic BLL with microcalcifications as an unexpected feature. The value and limitations of fine needle aspiration cytology in the diagnosis of nonneoplastic salivary gland lesions and the differential diagnosis of BLL are discussed.
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Enfermedad de Mikulicz/patología , Neoplasias de las Glándulas Salivales/patología , Adulto , Biopsia con Aguja , Calcinosis/patología , Diagnóstico Diferencial , Humanos , MasculinoRESUMEN
Malignant transformation of an adenolymphoma (Warthin's tumour) is a rare event. This paper presents a case of carcinoma arising in an adenolymphoma of the parotid gland.