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Introduction and importance: Paecilomyces species are rare fungi that are resistant to standard treatment and have increasing clinical relevance. The Purpureocillium lilacinum, formerly known as Paecilomyces lilacinus, has a unique sensitivity for the corneal surface. However, only a few cases have been documented globally. This case report presents the successful management of a patient with Paecilomyces lilacinus keratitis with topical voriconazole and oral itraconazole. Case presentation: A 40-year-old woman came to our ophthalmology clinic complaining of right eye pain due to a severe corneal infection in her right eye. Corneal scraping and identification of the cultured pathogen were performed, which revealed Paecilomyces lilacinus. The corneal infection improved after being treated with hourly topical voriconazole (10 mg/ml) and oral traconozole. Clinical discussion: Paecilomyces/Purpureocillium keratitis, which accounts for 5% of keratomycosis cases in tropical and subtropical areas, is extremely rare. It does not respond well to conventional antifungal treatment and frequently requires therapeutic surgery. Risk factors include wearing contact lenses, ocular trauma, ocular surgery, corticosteroids, and intraocular lens implantation. Conclusion: For the treatment of Paecilomyces lilacinus keratitis that is unresponsive to conventional antifungal medications, voriconazole may be helpful. Early organism detection and the appropriate therapy are necessary for the management of keratitis.
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BACKGROUND: Toll-like receptors (TLRs) are pattern-recognizing proteins involved in innate immunity and they seem to regulate both cancer progression and inhibition. In oral cancer, TLR activation has been linked to invasion. To define the role of TLR-2, TLR-4, and TLR-9 in oral tongue squamous cell carcinoma (OTSCC), we studied their expression in vivo in OTSCC tumor samples, as well as in vitro in cell invasion model. METHODS: We used immunohistochemistry to compare the expression of TLR-2, TLR-4, and TLR-9 in 21 primary Stage I-II OTSCCs, neck metastases, and recurrent tumors. In addition, we used myoma organotypic invasion assay to evaluate the effect of GIT27 (4,5-dihydro-3-phenyl-5-isoxasoleaceticacid) on the invasion of the HSC-3 OTSCC cell line. RESULTS: TLR-2, TLR-4, and TLR-9 were expressed in most tumors. Nuclear TLR-2 expression occurred more often in primary tumors than in neck metastases or recurrent tumors of the neck, whereas nuclear TLR-4 expression and cytoplasmic TLR-9 expression were higher in primary tumors than in local recurrent tumors. GIT27 did not affect the invasion of HSC-3 OTSCC cells, but a myoma organotypic invasion assay revealed that the expression of TLR-2 and TLR-4 was stronger in deeper-invading cells. CONCLUSIONS: TLR-2, TLR-4, and TLR-9 were expressed in primary tumors, neck metastases as well as in recurrent tumors of OTSCC. Thus, these receptors seem to play a role in both the development and progression of tongue carcinoma. These TLRs may also contribute to the invasive potential of OTSCC.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Receptores Toll-Like/biosíntesis , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/patología , Acetatos/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Oxazoles/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello , Receptor Toll-Like 2/biosíntesis , Receptor Toll-Like 4/biosíntesis , Receptor Toll-Like 9/biosíntesisRESUMEN
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past decades in many western countries. This trend is mainly attributed to the human papillomavirus (HPV). Cancer-related actions of immunological defense systems are being intensively researched. Human toll-like receptors (TLRs) are a family of pattern recognition receptors that participate in the immunological defense against pathogens, but their actions are also linked to cancer. The expression of TLRs in cervical epithelium alters both during the clearance of HPV infection and the HPV-induced neoplasia, but the expression of TLRs has not been studied in OPSCC. Thirty-five paraffin-embedded, formalin-fixed, squamous cell carcinoma tissue specimens were analyzed for TLRs 2, 3, 4, 5, 7, and 9 and HPV and p16 statuses. The TLR 9 expression was lower in HPV-positive tumors compared with HPV-negative tumors. TLR 7 was expressed in all cancer specimens, but elevated expression was evident in HPV and/or p16-positive tumors. The majority of p16-positive tumors did not express TLR 5, whereas its expression was stronger in p16-negative tumors. The results of in vitro analysis of five human OPSCC cell lines and one human oral tongue squamous cell carcinoma cell line agree with the in vivo trends: low levels of TLR 5 and high levels of TLR 7 in p16-positive OPSCC. Overall, TLR 7 and 9 expression patterns are demonstrated here to relate to the HPV status in vivo and TLR 5 and 7 expression patterns to the p16 status in vivo and in vitro.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Orofaríngeas/metabolismo , Tonsila Palatina/metabolismo , Papillomaviridae/genética , Infecciones por Papillomavirus/metabolismo , Receptores Toll-Like/metabolismo , Biomarcadores de Tumor/genética , Western Blotting , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Estudios de Casos y Controles , Proliferación Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , ADN Viral/genética , Humanos , Técnicas para Inmunoenzimas , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Pronóstico , Células Tumorales CultivadasRESUMEN
OBJECTIVES: The clinical behavior of oral tongue squamous cell carcinoma (OTSCC) can be unpredictable, and even small tumors may behave aggressively. Toll-like receptors (TLRs) are pattern-recognition molecules involved in innate immunity, and they are also expressed in many types of cancer. TLRs play an apparently pivotal role in some cancers related to tumor progression and, conversely, cancer inhibition, however their role in oral cancer is unclear. We therefore studied the expression of TLR-2, -4, -5, -7, and -9 in early-stage OTSCC. MATERIALS AND METHODS: Tissue microarray technique and immunohistochemistry was employed to define the expression of TLRs from the tumors of 73 consecutive patients with Stage I-II OTSCC. Immunoexpression scores were compared with patient and tumor related characteristics and survival. RESULTS: All TLRs were expressed in OTSCC tissue. High/strong TLR-2, -4, and -9 expression correlated with deeper tumor invasion. Cytoplasmic TLR-2 and -4 also correlated significantly with higher tumor grade, whereas high TLR-5 expression associated with lower tumor grade. High expression of TLR-9 correlated with advanced tumor size. Negative or mild TLR-5 expression predicted poor disease-specific survival. CONCLUSION: All the studied TLRs showed high expression in early-stage OTSCC. More importantly, TLR-2, -4, and -9 seemed to predict invasive tumor growth.