Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind integrins and are essential for integrin activation. We previously showed that β1 integrins are activated in metastatic prostate cancer (PCa) cells, increasing PCa metastasis to lymph nodes and bone. However, how β1 integrins are activated in PCa cells is unknown. In this study, we identified a novel mechanism of β1 integrin activation. Using knockdown experiments, we first demonstrated talin1, but not talin2, is important in β1 integrin activation. We next showed that talin1 S425 phosphorylation, but not total talin1 expression, correlates with metastatic potential of PCa cells. Expressing a non-phosphorylatable mutant, talin1S425A, in talin1-silenced PC3-MM2 and C4-2B4 PCa cells, decreased activation of β1 integrins, integrin-mediated adhesion, motility, and increased the sensitivity of the cells to anoikis. In contrast, re-expression of the phosphorylation-mimicking mutant talin1S425D led to increased β1 integrin activation and generated biologic effects opposite to talin1S425A expression. In the highly metastatic PC3-MM2 cells, expression of a non-phosphorylatable mutant, talin1S425A, in talin1-silenced PC3-MM2 cells, abolished their ability to colonize in the bone following intracardiac injection, while re-expression of phosphorylation-mimicking mutant talin1S425D restored their ability to metastasize to bone. Immunohistochemical staining demonstrated that talin S425 phosphorylation is significantly increased in human bone metastases when compared to normal tissues, primary tumors, or lymph node metastases. We further showed that p35 expression, an activator of Cdk5, and Cdk5 activity were increased in metastatic tumor cells, and that Cdk5 kinase activity is responsible for talin1 phosphorylation and subsequent β1 integrin activation. Together, our study reveals Cdk5-mediated phosphorylation of talin1 leading to β1 integrin activation is a novel mechanism that increases metastatic potential of PCa cells.
Non-Hodgkin's lymphoma (NHL) is rarely encountered in the larynx. We report another case of malignant lymphoma of larynx arising from mucosa-associated lymphoid tissue (MALT). CASE REPORTA 58-year-old Taiwanese woman was admitted to our hospital in August 1996 because of persistent hoarseness and a sensation of a lump in the throat for 2 months. Under indirect laryngoscopy, a right supraglottic, nonulcerative mass that was fish-flesh colored and about 1.5 cm in diameter was noted arising from the right aryepiglottic fold. Biopsy specimens revealed a nonulcerative mucosa infiltrated by a few atypical lymphocytes. The tumor persisted after supportive treatment, so direct laryngoscopy was performed again. Deep incision was done, and 6 pieces of tissue were taken, which revealed a submucosal tumor composed of small cleaved cells and large lymphoid cells with plasmacytoid differentiation. A thin grenz zone separated the main tumor from the overlying epithelium, but some atypical lymphoid cells infiltrated the overlying epithelium (Fig 1).Immunohistochemistry study demonstrated B-cell lineage. CT scan showed a laryngeal mass at right aryepiglottic fold, and 1 enlarged regional lymph node was noted. No other foci of lymphoma were found. A primary, diffuse, small cleaved and large cell laryngeal lymphoma was diagnosed. The patient was treated with a total dose of 3000 cGy of radiation. After 2000 cGy was given, the symptoms disappeared. Follow-up laryngoscopy was performed 6 months later; no recurrent tumor was seen. The patient was alive and well without symptoms of recurrence 1 year after treatment.
In this study, we incorporated silver nanowires (AgNWs) into poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) as a hole transport layer (HTL) for inverted perovskite solar cells (PVSCs). The effect of AgNW incorporation on the perovskite crystallization, charge transfer, and power conversion efficiency (PCE) of PVSCs were analyzed and discussed. Compared with neat PEDOT:PSS HTL, incorporation of few AgNWs into PEDOT:PSS can significantly enhance the PCE by 25%. However, the AgNW incorporation may result in performance overestimation due to the lateral charge transfer. The corrosion of AgNWs with a perovskite layer was discussed. Too much AgNW incorporation may lead to defects on the interface between the HTL and the perovskite layer. An extra PEDOT:PSS layer over the pristine PEDOT:PSS-AgNW layer can prevent AgNWs from corrosion by iodide ions.
Plasma-cell cheilitis is a rare inflammatory disorder of the lip characterized histologically by a band-like infiltrate of plasma cells in the upper dermis. It is considered an oral counterpart of plasma-cell balanitis. Clinically, it presents as a circumscribed, flat to slightly raised, eroded area of the lip. The cause of plasma-cell cheilitis is unknown, and the treatment is often disappointing. We describe a 55-year-old woman who had a long-lasting painful, swollen, and eroded area on her lips, which responded poorly to various topical treatments. Biopsy showed a band-like infiltrate composed mainly of mature plasma cells in the dermis. A diagnosis of plasma-cell cheilitis was made after excluding contact dermatitis, lichen planus, bacterial, fungal and spirochaete infections, and an extramedullary plasmacytoma. Dramatic improvements were observed after intralesional injections of corticosteroids. The lesion cleared up after two treatments, and there has been no recurrence in 1 year of follow-up.
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