Glutaminolysis and carcinogenesis of oral squamous cell carcinoma

Glutaminolysis is a crucial factor for tumor metabolism in the carcinogenesis of several tumors but has not been clarified for oral squamous cell carcinoma (OSCC) yet. Expression of glutaminolysis-related solute carrier family 1, member 5 (SLC1A5)/neutral amino acid transporter (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLDH) was analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I–III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry. SLC1A5/ASCT2 and GLS were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue, while GLDH was weakly detected. Compared with SIN I–III SLC1A5/ASCT2 and GLS expression were significantly increased in OSCC. GLDH expression did not significantly differ from SIN I–III compared with OSCC. This study shows the first evidence of glutaminolysis-related SLC1A5/ASCT2, GLS, and GLDH expression in OSCC. The very weak GLDH expression indicates that glutamine metabolism is rather related to nucleotide or protein/hexosamine biosynthesis or to the function as an antioxidant (glutathione) than to energy production or generation of lactate through entering the tricarboxylic acid cycle. Overcoming glutaminolysis by targeting c-Myc oncogene (e.g. by natural compounds) and thereby cross-activation of mammalian target of rapamycin complex 1 or SLC1A5/ASCT2, GLS inhibitors may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.     

A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas

Journal of Neuro-Oncology - Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in...     

Effects of Germline Pathogenic Variants,Cancer Subtypes,Tumor-related Characteristics,and Pregnancy-associated Diagnosis on Outcomes

BackgroundAlthough breast cancer (BC) is uncommon in women age ≤ 35 years, women in this age group may have more aggressive cancer subtypes and high-risk pathogenic variants (HRPVs). Higher recurrence and mortality rates in young patients may be related to differences in tumor biology, pathologic mutation status, or treatment. The purpose of this study was to evaluate germline mutation status and other factors that affect recurrence-free survival (RFS) and overall survival (OS) in young women with BC.Materials and MethodsThis was a retrospective study of women diagnosed with BC at age ≤ 35 years at Allina Health System from 2000 through 2017 (n = 306). Information was collected on germline mutation status, tumor characteristics (grade, hormone receptor, and human epidermal growth factor receptor 2), molecular subtype, pregnancy-associated cancers, and treatment. Survival analyses using Kaplan-Meier curves were conducted for RFS and OS.ResultsWith mean follow-up of 6.5 years, OS was 87.0% for invasive cancers, RFS was 84.7%; 69% obtained genetic testing, and 26.9% had HRPVs. There were no differences in RFS or OS between patients with HRPV versus unknown/low/moderate risk variants. Recurrence analysis showed increased recurrence rates in luminal B-like cancers followed by triple negative and human epidermal growth factor receptor 2-positive cancers (P = .041). Pregnancy-associated BC diagnoses, angiolymphatic invasion, and tumor stage were associated with reduced OS. In spite of young age at diagnosis, nearly one-third of patients did not receive germline genetic testing.ConclusionsSimilar survival patterns were found between women with HRPV versus no known mutations. Luminal B-like subtype, pregnancy-associated BC, angiolymphatic invasion, and cancer stage were associated with reduced OS.     

Sieben Tage alte,offene Fraktur des Daumengrundglieds mit Phlegmone

Die Unfallchirurgie -     

Injection of nonvariceal bleeding lesions of the upper gastrointestinal tract

In a prospective series 102 non-variceal upper GI bleeders were studied. An indication for endoscopic injection therapy was seen in 63 patients. In accordance with bleeding intensity, 27 patients were grouped as Forrest Ia, 37 as Forrest Ib, 8 as Forrest II with a "visible vessel" and 13 as Forrest II without one. Definitive hemostasis was achieved in almost 100% of the cases. Within the Forrest Ia group mortality was lowered to 11% as compared with 20% within the emergency surgery group. More than 80% of patients had at least one severe coexistent illness. The aim of endoscopic injection is to avoid surgery in high-risk patients.     

Uni- and bilateral lung transplantation: patient evaluation and selection. Vienna Lung Transplant Group]

Lung transplantation has been available as a therapeutic option for patients with end-stage lung disease for only a short period of time. Since this procedure is now being successfully performed with increasing frequency in various transplantation centers, we must now begin to consider transplantation as a therapeutic options in patients with lung diseases unresponsive to medical therapy. Physicians are required to know principles involved for determination of suitable candidates and operative procedures of choice. We report here our experiences of preoperative assessment of patients undergoing lung transplantation. Patient selection, indications, contraindications, choice of operation, appropriate timing for transplantation and preoperative rehabilitation methods are discussed. It is concluded that appropriate recipient selection remains an important determinant for the success of this treatment modality.