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Objective: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K-AKT-mTOR) signaling pathway is an important regulator of cell proliferation, survival, and motility. The gain or loss of function of proteins related to this pathway results in the neoplastic transformation in several types of cancers. This study aimed to evaluate the expression profile of the PI3K-AKT-mTOR pathway in patients with head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines., Study Design: The study involved 26 formalin-fixed paraffin-embedded tissue samples from patients with HNSCC. The analysis of immunohistochemical expression of PI3K, AKT, p-mTOR, and phosphatase and tensin homolog (PTEN) proteins was performed by a quantitative assessment. The in vitro gene and protein expression evaluation was performed by real-time polymerase chain reaction and Western blot assay, respectively, in the human cell lines SCC-9 and FaDu., Results: High levels of PI3K, AKT, and p-mTOR were found in most HNSCC tumors. Following this result, we observed low amounts or absence of PTEN in most samples. Additionally, the FaDu cells (pharynx) showed higher AKT expression but lower expression of p-mTOR compared with SCC-9 cells (oral cavity), which hints at a loco-anatomical relevance., Conclusion: Overall, this study found increased expression of the PI3K-AKT-mTOR pathway along with evident PTEN reduction in head and neck cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Examine the association between polymorphisms in the AKT1 and AKTIP genes and late-onset depression (LOD). Major depressive disorder is one of the most prevalent neuropsychiatric diseases. LOD is a disorder that starts after 65 years old. AKT1 is a downstream enzyme that has been implicated in the pathogenesis of neurotransmitter-related disorders, such as depression. The identification of a novel AKT1-binding protein (AKTIP) was pointed as an important new target. AKTIP binds directly to AKT1, enhancing the phosphorylation of regulatory sites, and this modulation are affected by AKT1 activation. The association of AKT1 and AKTIP polymorphisms with depressive symptoms was not investigated in LOD., Design: Genotype tagSNPs in the AKT1 and AKTIP in LOD patients and controls., Settings: An academic medical center., Participants: Sample composed by 190 outpatients with LOD and 77 healthy individuals., Measures: The participants were evaluated using Diagnostic and Statistical Manual IV criteria, MINI-PLUS and the Geriatric Depression Scale., Results: Our findings suggested an association between the tagSNP rs3730358 homozygous A/A (p = 0.006) and LOD. A strong association of allele A and increased association for LOD was demonstrated with tagSNP rs3730358 (p-value = 0.003)., Limitations: Limitation include composition of our control group, where the exclusion criteria generated a kind of super-healthy older group what might have produced a hidden stratification when compared with the LOD., Conclusion: This study is the first one to establish the association of the AKT1/AKTIP genes and LOD, and further studies are necessary to clarify the functional role of these proteins., (Copyright © 2013 John Wiley & Sons, Ltd.)

Chordomas are rare neoplasms arising from notochord remnants. Tyrosine kinase receptors (RTK) are altered in these lesions. We used a tissue microarray containing 58 chordomas to examine the expression of platelet-derived growth factor receptor (PDGFR)-α and PDGFR-β, epidermal growth factor receptor (EGFR), c-Met, c-Kit, pAKT, mammalian target of rapamycin, and HER2 by immunohistochemistry and fluorescence in situ hybridization. Most tumors were positive for PDGFR-α (92%), PDGFR-β (85%), c-Kit (77.4%), c-Met (96%), pAKT (82%), mammalian target of rapamycin (56%), HER2 (24%), and EGFR (26%) by immunohistochemistry. Amplifications or deletions could not be identified for HER2 or EGFR in the 13 cases available for fluorescence in situ hybridization analysis; however, chromosome 7 polysomy was detected in 29% of the cases. The only factor directly associated with a poorer survival rate was pAKT positivity (P = .042). The 5-year survival rate for patients with pAKT-negative chordomas was 100%, whereas it was 45% for patients with pAKT-positive chordomas. Our results confirm that RTKs are frequently altered in chordomas. Given the implications of pAKT positivity, RTK inhibitors might be efficacious, and drugs that inhibit AKT, alone or in combination with radiotherapy, could be an effective treatment for patients with refractory chordomas., (Copyright © 2013 Elsevier Inc. All rights reserved.)