Phosphoproteome profiling revealed abnormally phosphorylated AMPK and ATF2 involved in glucose metabolism and tumorigenesis of GH-PAs

Abstract

Purpose

Protein phosphorylation plays a key role in tumorigenesis and progression. However, little is known about the phosphoproteome profiles of growth hormone-secreting pituitary adenomas (GH-PAs). The aim of this study was to identify critical biomarkers and signaling pathways that might play important roles in GH-PAs and may, therefore, represent potential therapeutic targets.

Methods

The differential phosphoprotein expression patterns involved in GH-PAs were investigated by nano-LC–MS/MS in a group of samples. The phosphoprotein expression data were analyzed by bioinformatics. The expression levels of the candidate phosphorylated AMPK (ser496) and ATF2 (ser112) were validated by Western blot analysis in another group of samples.

Results

A total of 1213 phosphorylated protein sites corresponding to 667 proteins were significantly different between GH-PAs and healthy pituitary glands. Among these phosphorylated sites, 871 exhibited lower levels of phosphorylation in GH-PAs. Moreover, 140 novel phosphosites corresponding to 93 proteins were differentially phosphorylated between GH-PAs and healthy pituitary glands, 101 of which showed decreased phosphorylation in GH-PAs. The majority of differentially expressed phosphorylated proteins were significantly enriched in glycolysis and the AMPK signaling pathway in GH-PAs. The AMPK signaling pathway was demonstrated to be inhibited in GH-PAs by pathway activity analysis (z score = − 2.324). Notably, the phosphorylated levels of AMPK (ser496) and ATF2 (ser112) were significantly lower in GH-PAs than in healthy pituitary glands.

Conclusion

These findings suggest that decreased phosphorylation of the AMPK/ATF2 pathway may be critical for glucose metabolism and tumorigenesis in GH-PAs.

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PaRTNer: Patient Reported Outcomes and Financial Toxicity in Head and Neck Cancer A Pilot, Survey Based Study

Condition:   Head and Neck Cancer
Intervention:   Other: Demographics questionnaires and the FACT HN questionnaire
Sponsor:   Duke University
Not yet recruiting

https://ift.tt/2HYxmuY

PaRTNer: Patient Reported Outcomes and Financial Toxicity in Head and Neck Cancer A Pilot, Survey Based Study

Condition:   Head and Neck Cancer
Intervention:   Other: Demographics questionnaires and the FACT HN questionnaire
Sponsor:   Duke University
Not yet recruiting

https://ift.tt/2HYxmuY

Diagnostic Accuracy of Screening and Treatment of Post–Acute Coronary Syndrome Depression: A Systematic Review [Internet].

To evaluate (1) the diagnostic accuracy of selected depression screening instruments and strategies versus a validated criterion standard in adult patients within 3 months of an acute coronary syndrome (ACS) event and (2) the comparative safety and effectiveness of a broad range of pharmacologic and nonpharmacologic treatments for depression in adult patients who have received a criterion-based diagnosis of depression or had clinically important depressive symptoms using a validated depression scale and who are within 3 months of an ACS event.

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Effect of Hot Rolled Substrate of Hydrogen Reduction on Interfacial Reaction Layer of Hot-dip Galvanizing

Publication date: September 2018
Source:Journal of Materials Processing Technology, Volume 259
Author(s): Guangxin Wu, Chuang Guan, Ning Tan, Jieyu Zhang
The effect of morphology of substrate on intermetallic layer is studied in this work by combining the hydrogen reduction descaling of hot rolled steel and galvanizing process. The results show that the morphology of iron reduced at different temperatures can be divided into porous and dense iron surface. The interfacial reaction layer on steel strip with porous iron is composed of ξ phase and δ phase, and the phase in coating is invariable with the increasing of soaking time. However, the interfacial reaction layer on steel strip with dense iron is considered to be Fe2Al5Znx intermetallic layer. As the time goes up, a columnar ξ phase forms on the intermetallic layer of steel strip reduced at 700 ºC and the Fe-Al intermetallic layer disappears gradually. In addition, the bursting phenomenon of intermetallic layer occurs after dipping for 10s on steel strip reduced at 800 ºC, and the δ phase forms on the interface between the "outburst" Fe-Al phase and substrate. The possible mechanisms involved in the formation of Fe-Al and Fe-Zn alloys were also discussed.



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Report of a unique case of myoepithelial carcinoma of left parotid gland with metachronous bilateral cavernous sinus metastasis

Publication date: Available online 23 April 2018
Source:Journal of the Egyptian National Cancer Institute
Author(s): Rambha Pandey, Rituparna Biswas, Mukurdipi Ray, Prashant P. Ramteke, Ekta Dhamija, Anirban Halder
Myoepithelial carcinoma (MC) is a rare, locally aggressive malignant neoplasm of the salivary glands. Only few evidences on its metastatic behavior are available in the literature. We herein present a unique case of MC of left parotid gland which metastasized to bilateral cavernous sinuses. The patient was successfully treated with palliative radiotherapy and chemotherapy.



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Selective internal radiation therapy (SIRT) as treatment for hepatic metastases of uveal melanoma: a Finnish nation-wide retrospective experience.

Related Articles

Selective internal radiation therapy (SIRT) as treatment for hepatic metastases of uveal melanoma: a Finnish nation-wide retrospective experience.

Acta Oncol. 2018 Apr 23;:1-8

Authors: Tulokas S, Mäenpää H, Peltola E, Kivelä T, Vihinen P, Virta A, Mäkelä S, Kallio R, Hernberg M

Abstract
BACKGROUND: In Finland, selective internal radiation therapy (SIRT) is at present the preferred first-line loco-regional therapy for uveal melanoma patients with hepatic metastases not suitable for surgery. We retrospectively evaluate the outcome and safety of SIRT in this group of patients.
MATERIAL AND METHODS: Yttrium-90 microspheres were delivered via the hepatic artery into the circulation of metastases from uveal melanoma in 18 patients with a predicted life expectancy of more than three months in three Finnish tertiary referral centers between November 2010 and December 2015. Progression-free survival (PFS), toxicity and overall survival (OS) were evaluated. Patients with historical uveal melanoma without extrahepatic metastases, who had received systemic chemotherapy as first-line treatment for their hepatic metastases at the Helsinki University Hospital between January 2006 and May 2010, were used as a historical control group.
RESULTS: Partial response and stable disease were observed in three (17%) and eight (44%) patients, respectively; one patient was not evaluable for response. Median PFS after SIRT was 5.6 (range, 1.3-40.8) months. Median OS after SIRT was 13.5 (range, 3.6-44.8) months compared with 10.5 (range, 3.0-16.5; p = .047) months for the historical chemotherapy group. Among patients who received SIRT as first-line treatment, the median OS was 18.7 (range, 8.2-44.8) months, significantly longer than that of the chemotherapy group (10.5 months, p = .017). There were no treatment-related deaths. Toxicity was mainly WHO grade 1-2 and self-limited.
CONCLUSION: SIRT is a feasible and safe treatment for liver metastases in patients with uveal melanoma.

PMID: 29683787 [PubMed - as supplied by publisher]

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