Mutations in TP53, the gene that encodes the tumour suppressor p53, are found in 50% of human cancers, and increased levels of its negative regulators MDM2 and MDM4 (also known as MDMX) downregulate p53 function in many of the rest. Understanding p53 regulation remains a crucial goal to design broadly applicable anticancer strategies based on this pathway. This Review of in vitro studies, human tumour data and recent mouse models shows that p53 post-translational modifications have modulatory roles, and MDM2 and MDM4 have more profound roles for regulating p53. Importantly, MDM4 emerges as an independent target for drug development, as its inactivation is crucial for full p53 activation.

Regulating the p53 pathway: in vitro hypotheses, in vivo veritas

Alterations in gene sequences, expression levels and protein structure or function have been associated with every type of cancer. These 'molecular markers' can be useful in detecting cancer, determining prognosis and monitoring disease progression or therapeutic response. But what is the best way to identify molecular markers and can they be easily incorporated into the clinical setting?

Emerging molecular markers of cancer

Prognostic Factors in Non-small Cell Lung Cancer: A Decade of Progress

https://www.jto.org/article/S1556-0864(15)31543-4/pdf

The IASLC Lung Cancer Staging Project: proposals regarding the relevance of TNM in the pathologic staging of small cell lung cancer in the forthcoming (seventh) edition of the TNM classification for lung cancer.

Parapneumonic effusions occur in 20 to 40% of patients who are hospitalized with pneumonia. The mortality rate in patients with a parapneumonic effusion is higher than that in patients with pneumonia without a parapneumonic effusion. Some of the excess mortality is due to mismanagement of the parapneumonic effusion. Characteristics of patients that indicate that an invasive procedure will be necessary for its resolution include the following: an effusion occupying more than 50% of the hemithorax or one that is loculated; a positive Gram stain or culture of the pleural fluid; and a purulent pleural fluid that has a pH below 7.20 or a glucose below 60, or has a lactic acid dehydrogenase level of more than three times the upper normal limit for serum. Patients with pneumonia and an effusion of more than minimal size should have a therapeutic thoracentesis. If the fluid cannot be removed with a therapeutic thoracentesis, a chest tube should be inserted and consideration be given to the intrapleural instillation of fibrinolytics. If the loculated effusion persists, the patient should be subjected to video-assisted thoracoscopic surgery, and if the lung cannot be expanded with this procedure, a full thoracotomy with decortication should be performed. The definitive procedure should be performed within 14 d.

Parapneumonic effusions and empyema.

Results of surgical treatment of non-small cell lung cancer: validation of the new postoperative pathologic TNM classification.

MDM2 gene amplification: a new independent factor of adverse prognosis in non-small cell lung cancer (NSCLC).

Objective: The aim of the present study is to evaluate the lung function before and after the lung decortication in patients with chronic pleural empyema (CPE). Methods: Twenty-six patients with diagnosis of CPE were evaluated in a prospective manner by lung perfusion scintigraphy, blood gas analysis and spirometry before and 35 weeks (^17) after the lung decortication. Results: Preoperative scintigraphy showed reduction of lung perfusion on the affected side to 24.5% (^12.6%) in 11 right side empyemas (predicted value 55%) and to 18% (^8%) in 15 left side empyemas (predicted value 45%). The postoperative measurements showed improvement in perfusion to 45.2% (^7.7%) in patients with right side empyema and 34.1% (^8.5%) with the left side affection. The preoperative vital capacity (VC) was reduced to 62.3% (^13.8%) of the predicted value and forced expiratory volume in 1 s (FEV1) to 50% (^15.5%) of the predicted value. Postoperatively, slight improvement was achieved to 79.8 % (^12.9%) for VC and 69.2% (^12.7%) for FEV1 . Blood gas analysis showed decreased values in majority of the patients before operation and significant improvement in postoperative evaluation. Conclusions: Perfusion and spirometry improves significantly in patients with CPE after the lung decortication but function of the affected lung remains impaired. There was no influence of the age, gender, side of the disease, bacteriology or duration of the empyema before operation on lung function. q 2002 Elsevier Science B.V. All rights reserved.

/pdf/decortication-in-chronic-pleural-empyema-effect-on-lung-o4627vgsdo.pdf

Jan Skokowski

Papers

Results of surgical treatment of non-small cell lung cancer: validation of the new postoperative pathologic TNM classification.

MDM2 gene amplification: a new independent factor of adverse prognosis in non-small cell lung cancer (NSCLC).

Decortication in chronic pleural empyema — effect on lung function

Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer.

The influence of blood transfusion on survival in operated non-small cell lung cancer patients.