Purpose A key issue in cancer is apoptosis resistance. However, little is known about the transcription factors which contribute to cellular survival of head and neck squamous cell carcinoma (HNSCC). Experimental design Three batches (54, 64, and 38) of HNSCC specimens were used for cellular and molecular analyses in order to determine the major molecular signaling pathways for cellular survival in HNSCC. Animal models (cell culture and xenografts) were employed to verify the importance of apoptosis resistance in HNSCC. Results Inhibitor of differentiation (Id) family member, Id1, was significantly up-regulated in clinical HNSCC specimens and acted to protect keratinocytes from apoptosis. Transfection of HNSCC cells with Id1 in vitro induced the phosphorylation of Akt (p-Akt) via phosphoinositide kinase-3 (PI3K) and increased the expression of survivin via nuclear factor kappa B (NF-κB). Blockage of the both pathways by specific inhibitors (LY294002 and IκBαM, respectively) abrogated Id1-induced cell survival of keratinocytes. In vivo studies demonstrated that increased expression of Id1 allowed non-tumorigenic keratinocytes (Rhek-1A) to become tumorigenic in nude mice by increased expression of survival genes such as p-Akt and survivin. More importantly, short interfering RNA (siRNA) for Id1 significantly reduced HNSCC tumorvolume of HNSCC in xenograft studies. Analysis of clinical data verified the importance of the Id1 downstream molecule, survivin, in the prognosis of HNSCC patients. Conclusions The above data, taken together, suggest that Id1 and its downstream effectors are potential targets for treatment of HNSCC because of their contribution to apoptosis resistance.
BackgroundCervical lymph node metastasis of papillary thyroid carcinoma (PTC) is common. However, whether undergoing prophylactic central lymph node (CLN) dissection or lateral lymph node (LLN) dissections to prevent metastasis is still controversial. This study aimed to retrospectively investigate the risk factors of LLN metastasis in clinical lymph node-negative (cN0) PTC patients.MethodsWe retrospectively studied 783 lymph node-negative (cN0) PTC patients who underwent total thyroidectomy plus CLN dissection and LLN dissection.ResultsThe rates of CLN and LLN metastases were 68.2 and 47.4%, respectively. Large tumor size (> 20 mm) had a fourfold higher risk of LLN metastasis compared with small tumor size (≤ 20 mm; OR = 4.082, 95% CI 2.646–6.289; P = 0.001). Patients with tumor in the upper lobe had ~ 3-fold higher risk of LLN metastasis compared with patients with tumor in other locations (OR = 2.874, 95% CI 1.916–4.310; P = 0.001). Multifocality and extrathyroidal extension indicated a twofold higher risk of LLN metastasis. Having ≥ 2 CLN metastases dramatically increased the risk of LLN metastasis, compared with those with < 2 CLN metastases (OR = 6.536, 95% CI 4.630–9.259; P = 0.001).ConclusionsLarge tumor size (> 20 mm), tumor located in the upper lobe, multifocality, extrathyroidal extension, and ≥ 2 CLN metastases may increase the risk of LLN metastasis in cN0 PTC patients.
Background Sialadenoma papilliferum (SP) is an extremely rare benign neoplasm of salivary glands. To explore and define the clinicopathological features of SP, we retrospectively analyzed 89 cases previously reported and five new cases. Methods The clinical features, histopathology, immunohistochemistry and molecular analysis of our cases were further performed and the related literatures were reviewed and analyzed. Results Combining 89 cases from the literature with our cases, the hard palate was the most common locations for SP. However, two of our cases were rarely located in the esophageal mucosa. Among all cases, the male gender was more affected, with the average age and median age of 61.8 and 62 years, respectively. Conventional histomorphologically, SP was characterized by complex papillary structures with a biphasic growth pattern of exophytic squamous component and endophytic glandular component. The glandular structures were lined by a double layer of epithelium composed of flattened or cuboidal basal cells and a cuboidal or columnar luminal cells formed papillary infoldings into the ductal lumina. Immunohistochemically, the luminal epithelial configurations showed strong expression of CK7 along the luminal cell membrane, while the basal myoepithelia displayed strong nuclear p63 expression. In both the glandular and squamous tumour components showed BRAF V600E-positive immunostaining and BRAF V600E mutation. Conclusion For the first time, we have comprehensively aggregated and analyzed 90 cases sialadenoma papilliferum from almost all previous publications, and further explored the clinicopathological features of SP; concordantly, this study demonstrated that SP shows a papillomatous growth pattern with exophytic and endophytic proliferation of ductal epithelium composed of double-layered cells harboring BRAF V600E mutation. Additionly, adequate treatment for SP is surgical excision, with a favorable prognosis in patients.
SWItch/Sucrose NonFermentable (SWI/SNF) is a set of multi-subunits chromatin remodeling complexes, playing important roles in a variety of biological processes. Loss-of-function mutations in the genes encoding SWI/SNF subunits have been reported in more than 20% of human cancers. Thus, it was widely considered as a tumor suppressor in the past decade. However, recent studies reported that some genes encoding subunits of SWI/SNF complexes were amplified and play oncogenic roles in human cancers. In present study, we summarized the genetic alteration spectrum of SWI/SNF complexes, and firstly systematically estimated both the copy number variations and point mutations of all 30 genes encoding the subunits in this complex. Additionally, the bioinformatics analyses were performed for two significantly amplified genes, ACTL6A and BRD9, to investigate their oncogenic roles in human cancers. Our findings may lay a foundation for the discovery of potential treatment targets in SWI/SNF complexes of cancers.
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