In order to better understand the role of HIF-1α in the proliferation of the retinoblastoma cells, a siRNA knockdown of HIF-1α followed by a proliferation assay was performed. Further sequencing was ...then carried out in order to assess knockdown efficiency and expression of HIF-1α. Upregulation of HIF-1α gene expression in CoCl
2
-treated retinoblastoma cells was demonstrated via melting curve analysis from PCR tests and was further analyzed using western blot and densitometry analysis. Reduction of HIF-1α expression in retinoblastoma, post HIF-1α knockdown, was observed after siRNA transfection into Y-79 cells. Knockdown of HIF-1α resulted in a significant decrease in proliferation thereby demonstrating that HIF-1α is involved in promoting survival and proliferation in retinoblastoma cells. Stabilization of HIF-1α in retinoblastoma cells using CoCl
2
was unsuccessful.
BACKGROUND:The class III histone deacetylase SIRT1 is overexpressed in many malignancies and has been implicated in inactivating proteins that are involved in tumor suppression and DNA damage repair. ...In the current study, we examined the expression of SIRT1 in normal epithelium (NE) compared with ocular surface squamous neoplasia (OSSN) to elucidate a possible role for SIRT1 in the development or progression of this malignancy.
METHODS:We examined SIRT1 expression by immunohistochemistry in 47 cases of OSSN and 10 specimens of NE. Our sample included 11 benign lesions (papillomas), 25 cases of conjunctival intraepithelial neoplasia, and 11 malignant lesions of squamous cell carcinoma. The extent of staining and intensity was scored and the combined raw data were then converted to the German Immunoreactive Score.
RESULTS:Nuclear and cytoplasmic expression of SIRT1 was observed in all cases of OSSN. For the NE specimens, 50% showed negative expression and 30% weak expression, and 20% were considered significantly immunoreactive. The differential expression of SIRT1 between NE and OSSN was statistically significant (P < 0.0001). Additionally, when the staining pattern in cases of conjunctival intraepithelial neoplasia was evaluated, the staining of the more differentiated surface cells was remarkably weaker compared with the cells located closer to the basal membrane.
CONCLUSIONS:SIRT1 may play an important role in the development and progression of epithelial tumors of the conjunctiva. Further research into the potential of SIRT1 as a novel therapeutic target is warranted.
Purpose: To examine the immunohistochemical profile of heat shock protein 90 (Hsp90) in uveal melanoma and the cytotoxicity of an
Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in ...uveal melanoma cell lines.
Experimental Design: Hsp90 expression was determined by immunohistochemistry in 44 paraffin-embedded sections of primary human uveal melanoma
and in five uveal melanoma cell lines (92.1, OCM-1, MKT-BR, SP6.5, and UW-1). Sulforhodamine B–based proliferation assay was
used to compare uveal melanoma cell growth with a range of concentrations of 17-AAG. Changes in cell migration, invasion,
cell cycle fractions, and apoptotic activity were also evaluated. Expression of intracellular proteins was determined by Western
blot analysis after 17-AAG exposure.
Results: Immunohistochemical expression of Hsp90 was identified in 68% of the paraffin-embedded sections and significantly associated
with largest tumor dimension ( P = 0.03). 17-AAG significantly reduced the proliferation rates of uveal melanoma cell lines, with concentrations of 100 to
0.1 μmol/L. 17-AAG also significantly reduced the migratory and invasive capabilities of uveal melanoma cell lines. Cell cycle
analysis showed that 17-AAG induced accumulations of cells in G 1 . Caspase-3 protease activity analysis, a marker for apoptosis, showed a significant increase after drug exposure. The cytotoxic
effect of 17-AAG was associated with decreased levels of phosphorylated Akt and cyclin-dependent kinase 4.
Conclusions: The immunohistochemical expression of Hsp90 in uveal melanoma indicates worse prognosis. To the best of our knowledge, this
is the first report showing the inhibitory effect on uveal melanoma cells using 17-AAG to target Hsp90. Therefore, Hsp90 may
be used as a potential target for treatment of patients with uveal melanoma.
Infiltrating Syringomatous Adenoma of the Nipple Odashiro, Maçanori; Lima, Marilana G.; Miiji, Luciana N. ...
The breast journal,
July/August 2009, 2009 Jul-Aug, 2009-07-00, 20090701, Letnik:
15, Številka:
4
Journal Article
Recenzirano
Odprti dostop
: Infiltrating syringomatous adenoma of the nipple is a rare, benign, locally invasive tumor with recurrence potential, showing sweat duct differentiation. It can clinically, radiologically and ...pathologically mimic cancer. Histopathologically, it must be distinguished from florid papillomatosis, adenosquamous carcinoma, adenoid cystic carcinoma and sclerosing syringomatous carcinoma. A 44‐year‐old woman presented with pain on the right nipple for 7 days. On physical exam there was an irregular nodule on nipple area with edema. The skin was intact. The ultrasound showed a hypoechoic irregular nodule measuring 7.5 mm in the nipple area. The mammography was unspecific. The lesion was surgically removed and histopathologically, the tumor was composed of ducts and tubules lined with a double‐layered epithelial cells. The lining cells were small, cuboidal with a central nuclei and eosinophilic nuclei. The stroma was dense with lymphocytes and plasma cells, and compressed many of the ducts that contained a comma or tadpole‐shape, giving an impression of a syringoma. Some ducts were slightly dilated with squamous metaplasia. Some of these cysts were connected with the overlying epidermis. Mitotic figures were rare and no pleomorfism or hyperchromasia was observed. At the periphery, the ducts invaded muscular fibers of the nipple. The surgical margins were free of neoplastic involvement. Patient has no signs of progression of disease in 1 year of follow‐up.
Uveal melanoma (UM) cell lines, when exposed to blue light in vitro, show a significant increase in proliferation. In order to determine if similar effects could be seen in vivo, we investigated the ...effect of blue light exposure in a xenograft animal model of UM.
Twenty New Zealand albino rabbits were injected with 1.0 x 10(6) human UM cells (92.1) in the suprachoroidal space of the right eye. Animals were equally divided into two groups; the experimental group was exposed to blue light, while the control group was protected from blue light exposure. The eyes were enucleated after sacrifice and the proliferation rates of the re-cultured tumor cells were assessed using a Sulforhodamine-B assay. Cells were re-cultured for 1 passage only in order to maintain any in vivo cellular changes. Furthermore, Proliferating Cell Nuclear Antigen (PCNA) protein expression was used to ascertain differences in cellular proliferation between both groups in formalin-fixed, paraffin-embedded eyes (FFPE).
Blue light exposure led to a statistically significant increase in proliferation for cell lines derived from intraocular tumors (p < 0.01). PCNA expression was significantly higher in the FFPE blue light treated group when compared to controls (p = 0.0096).
There is an increasing amount of data suggesting that blue light exposure may influence the progression of UM. Our results support this notion and warrant further studies to evaluate the ability of blue light filtering lenses to slow disease progression in UM patients.
Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in immunocompetent individuals in Brazil. Ocular infection by PCM is rare; however, when infection does occur, the most common ...ocular sites involved are eyelid and conjunctiva. A 68-year-old white male presented with a 2-month history of a painless, ulcerated, infiltrative and diffuse whitish lesion located on the right inferior eyelid. A clinical diagnosis of malignant tumor, possibly squamous cell carcinoma, was made. The histopathologic examination showed a hyperplastic epithelium with inflammatory infiltrate of lymphocytes, plasma cells, neutrophils and histiocytes. Large numbers of giant cells were also present. Periodic acid Schiff and Grocott (silver methenamine) stains showed several large round structures with peripheral lateral small budding cells that resembled a “ship’s wheel”. No multinucleated fungi were seen. The fungi varied in size and small forms were round and single fungal structures. A diagnosis of paracoccidioidomycosis was made PCM eyelid infection is rare and can simulate carcinoma both clinically and histopathologically.
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