Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment

Cancer cells show a broad spectrum of bioenergetic states, with some cells using aerobic glycolysis while others rely on oxidative phosphorylation as their main source of energy. In addition, there is mounting evidence that metabolic coupling occurs in aggressive tumors, between epithelial cancer cells and the stromal compartment, and between well-oxygenated and hypoxic compartments. We recently showed that oxidative stress in the tumor stroma, due to aerobic glycolysis and mitochondrial dysfunction, is important for cancer cell mutagenesis and tumor progression. More specifically , increased autophagy/mitophagy in the tumor stroma drives a form of parasitic epithelial-stromal metabolic coupling. These findings explain why it is effective to treat tumors with either inducers or inhibitors of autophagy, as both would disrupt this energetic coupling. We also discuss evidence that glutamine addiction in cancer cells produces ammonia via oxidative mitochondrial metabolism. Ammonia production in cancer cells, in turn, could then help maintain autophagy in the tumor stromal compartment. In this vicious cycle, the initial glutamine provided to cancer cells would be produced by autophagy in the tumor stroma. Thus, we believe that parasitic epithelial-stromal metabolic coupling has important implications for cancer diagnosis and therapy, for example, in designing novel metabolic imaging techniques and establishing new targeted therapies. In direct support of this notion, we identified a loss of stromal caveolin-1 as a marker of oxidative stress, hypoxia, and autophagy in the tumor microenvironment, explaining its powerful predictive value. Loss of stromal caveolin-1 in breast cancers is associated with early tumor recurrence, metastasis, and drug resistance, leading to poor clinical outcome

FDG PET/CT in the imaging of mediastinal masses

WorkshopConference Theme: Diseases of the Chest and Hear

PET Scans for Staging and Restaging in Diffuse Large B-Cell and Follicular Lymphomas

Positron emission tomography (PET)-CT was recommended in updated international guidelines for staging/restaging of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). In FL, PET was previously regarded as a research application only. This review concentrates on new publications related to PET in these diseases. In DLBCL, PET appears appropriate for staging using prognostic indices established with CT and baseline PET parameters, e.g. metabolic tumour volume, are prognostic of outcome. Early complete metabolic response (CMR) predicts end-of-treatment CMR with excellent prognosis. Patients without CMR at interim should not have treatment altered, but have a worse prognosis, and patients with other high risk features may need closer monitoring. The end-of-treatment scan is confirmed as the standard for remission assessment using Deauville criteria, which are also predictive for patients undergoing ASCT. In FL, PET is more sensitive for staging than CT but misses bone marrow involvement. PET-CT identifies patients at risk of progression after induction chemotherapy better than CT

Non-Hodgkin’s lymphoma—PET for diagnosis and treatment evaluation

Background. F-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is an internationally recognized standard for the diagnosis and treatment guidance in non-Hodgkin's lymphoma (NHL). The use of PET in NHL is also becoming increasingly established in Germany. Objective. Presentation of clinically relevant indications for FDG-PET/CT in the treatment of patients with indolent and aggressive NHL. Material and methods. Evaluation of relevant guidelines, examples of typical findings, discussion of clinically relevant expert recommendations and the reimbursement situation in Germany. Results. The FDGPET/CT procedure is the most accurate non-invasive method for staging and restaging in NHL. International guidelines provide well-founded recommendations for the targeted use of FDG PET/CT in NHL patients. The indications for and extent of radiotherapy for follicular lymphoma are largely dependent on the PET/CT findings. In aggressive NHL the interim results of the OPTIMAL>60 study raise the expectation of a survival benefit after radiotherapy of PET-positive bulk residues. The measurement of total metabolic tumor volume by PET provides outstanding prognostic information. The availability of PET in Germany is still limited by regional differences in reimbursement policies of statutory health insurance providers. Conclusion. The selective use of FDG PET/CT in patients with NHL is an international standard of care that facilitates staging, risk stratification, assessment of treatment response and treatment guidance. In the light of international recommendations and national S3 guidelines, earlier negative decisions by the Federal Joint Committee (G-BA) on PET in lymphomas need to be reconsidered