Patterns of dopamine transporter imaging in subtypes of multiple system atrophy.

OBJECTIVES: To investigate the differences in the pattern of striatal (caudate and putamen) dopamine transporter (DAT) loss in a multiple system atrophy (MSA) cohort, based on the clinical variants parkinsonian subtype (MSA-P) and cerebellar subtype (MSA-C) via (11)C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11 C-CFT) positron emission tomography (PET) imaging. MATERIALS AND METHODS: One hundred and six subjects (forty-one patients with probable MSA-P; forty patients with probable MSA-C; twenty-five healthy controls) underwent 11 C-CFT PET. Subregional 11 C-CFT uptake of bilateral caudate, anterior putamen, and posterior putamen was calculated respectively to measure the striatal dopaminergic function. RESULTS: Significant decrease in DAT binding in striatum was revealed in patients with MSA-C and MSA-P compared to normal controls (all regions, MSA-C vs controls, P < .0001; MSA-P vs controls, P < .0001). DAT reduction was more pronounced in MSA-P patients than that in MSA-C patients (all regions, P < .0001). Eleven of forty MSA-C patients displayed no DAT loss, whereas striatal DAT loss was evident in all MSA-P patients. MSA-P subtype showed a more obvious anteroposterior gradient of DAT loss and more asymmetric dopaminergic dysfunction compared to MSA-C patients. CONCLUSION: The subtypes of MSA studied here show significantly different spatial/anatomic patterns of striatonigral degeneration which may provide insights into their disease pathophysiology. Specifically, MSA-P patients exhibit an uneven and much greater pronounced loss of dopamine innervation, while a relatively uniform pattern is revealed in patients with the MSA-C. Furthermore, the typical reduction in DAT 11 C-CFT binding in striatum is not present in all MSA-C patients, with a minority of cases showing normal DAT binding.

SATB1 promotes tumor metastasis and invasiveness in oral squamous cell carcinoma.

OBJECTIVE: Our aim is to evaluate the expression of SATB1 in human oral squamous cell carcinomas (OSCC) and its role in the invasiveness and metastasis of OSCC. SUBJECTS AND METHODS: A human OSCC tissue microarray was used to evaluate the expression pattern of SATB1. SATB1 mRNA knockdown was performed in human OSCC cell lines SCC25 and Cal27 to assess the function of SATB1 in the invasiveness and metastasis of OSCC. RESULTS: SATB1 is highly expressed in human OSCC determined by immunohistochemistry, and its nuclear/cytoplasmic ratio of histoscore is significantly correlated with patients' prognosis. Reduced cell motility, invasiveness, expression of epithelial to mesenchymal transition (EMT) markers (N-cadherin and ß-catenin), and elevated expression of epithelial markers were observed in SATB1-knockdown cells in in vitro studies. Depletion of SATB1 also restored a cobblestone-like morphology in TGF-ß1-treated cells. CONCLUSIONS: These findings suggest SATB1 may play an important role in OSCC invasiveness and metastasis.

Preliminary Extracellular Vesicle Profiling in Drainage Fluid After Neck Dissection in OSCC.

Lymph node metastasis is related to poor prognosis in oral squamous cell carcinoma (OSCC), and few studies have explored the relevance of postoperative drainage fluid (PDF) in metastasis. Extracellular vesicles (EVs) are nanosized vesicles that can transfer oncogenic molecules to regulate tumorigenesis. However, the proteomic profile of postoperative drainage fluid-derived EVs (PDF-EVs) in OSCC has not been elucidated. Herein, we collected drainage fluid from OSCC patients after neck dissection to investigate the difference in PDF-EVs between patients with metastatic lymph nodes (the LN+ group) and nonmetastatic lymph nodes (the LN- group). The proteomic profile of PDF-EVs from the LN+ and LN- groups was compared using label-free liquid chromatography tandem-mass spectrometry-based protein quantification. The results revealed that PDF-EVs were mainly derived from epithelial cells and immune cells. A total of 2,134 proteins in the PDF-EVs were identified, and 313 were differentially expressed between the LN+ and LN- groups. Metabolic proteins, such as EHD2 and CAVIN1, were expressed at higher levels in the LN+ group than in the LN- group, and the levels of EHD2 and CAVIN1 in the postoperative drainage fluid were positively correlated with lymph node metastasis. Our study revealed previously undocumented postoperative drainage fluid-associated proteins in patients with metastatic OSCC, providing a starting point for understanding their role in metastatic and nonmetastatic OSCC.

STAT3 Induces Immunosuppression by Upregulating PD-1/PD-L1 in HNSCC.

Head and neck cancer is one of the most prevalent cancers around the world. Head and neck squamous cell carcinoma (HNSCC) accounts for nearly 90% of head and neck cancer. In recent years, significant advances have been made in immunotherapy for HNSCC. Although some clinical trials targeting immune checkpoints have shown success, the molecular mechanism for regulation of programmed death 1 (PD-1) and its ligand (PD-L1) is partially understood. In an effort to explore the effect of activation of signal transducers and activators of transcriptions (STAT3) on PD-1/PD-L1, the expression and correlation between phosphorylation of STAT3 and PD-1/PD-L1 were determined with immunostaining of human and mouse HNSCC tissue sections. PD-1/PD-L1 overexpression was found to be significantly associated with p-STAT3 in human and mouse HNSCC. Targeting STAT3 by a small molecule effectively inhibited the expression of PD-L1 in the CAL27 cell line. Furthermore, we found that blockade of STAT3 signaling downregulated PD-1/PD-L1 in a Tgfbr1/Pten 2cKO HNSCC mouse model. These findings suggest that STAT3 signaling plays an important role in PD-1/PD-L1 regulation and the antitumor immune response of HNSCC.