Cancer cells undergo unlimited progression and survival owing to activation of oncogenes. However, support of the tumor microenvironment is essential to the formation of clinically relevant tumors. Recent evidence indicates that the tumor microenvironment is a critical regulator of immune escape, progression, and distant metastasis of cancer. Moreover, the tumor microenvironment is known to be involved in acquired resistance of tumors to various therapies. Despite significant advances in chemotherapy and radiotherapy, occurrence of therapeutic resistance leads to reduced efficacy. This review highlights myeloid cells, cancer-associated fibroblasts, and mesenchymal stem cells consisting of the tumor microenvironment, as well as the relevant signaling pathways that eventually render cancer cells to be therapeutically resistant.

The p21-activated Ser/Thr kinase 1 (PAK1) kinase has an essential role in tumorigenesis and cell survival in many cancers, but its regulation is not fully understood. In this study, we showed that in response to irradiation of lung cancer cells, PAK1 was upregulated, tyrosine phosphorylated, and translocated to the nucleus. Tyrosine phosphorylation relied upon JAK2 kinase activity and was essential for PAK1 protein stability and binding to Snail. This radiation-induced JAK2-PAK1-Snail signaling pathway increased epithelial-mesenchymal transition (EMT) by regulating epithelial and mesenchymal cell markers. Notably, JAK2 inhibitors mediated radiosensitization and EMT blockade in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that JAK2 phosphorylates and stabilizes functions of PAK1 that promote EMT and radioresistance in lung cancer cells, with additional implications for the use of JAK2 inhibitors as radiosensitizers in lung cancer treatment.

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There are concerns about secondary extracorporeal membrane oxygenation (ECMO) catheter infections in bacteremic patients. We investigated the association between blood stream infection (BSI) and ECMO catheter colonization. From January 2012 to August 2014, 47 adults who received ECMO support were enrolled. The ECMO catheter tip was cultured at the end of the ECMO procedure. The enrolled patients were classified into two groups according to the presence of BSI during ECMO support and analyzed with respect to ECMO catheter colonization. Of 47 cases, BSI during ECMO was identified in 13 patients (27.7 %). ECMO catheter colonization was identified in 6 (46.2 %) patients in the BSI group and 3 (8.8 %) in the non-BSI group. BSI during ECMO support was independently associated with ECMO catheter colonization [odds ratio (OR) 5.55; 95 % confidence interval (CI) 1.00-30.73; p = 0.049]. The organisms colonizing ECMO catheters in the setting of primary BSI were predominantly Gram-positive cocci and Candida species. Acinetobacter baumannii was the most common colonizing pathogen in the setting of secondary BSI. All the organisms colonizing ECMO catheters were multi-drug resistant organisms, including methicillin-resistant S. aureus, Candida glabrata, and carbapenem-resistant A. baumannii. ECMO catheters may become contaminated with multi-drug resistant pathogens in the presence of BSI. Therefore, ECMO should be applied cautiously in septic patients with bacteremia caused by multi-drug resistant pathogens.

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Hyperthermia is a cancer treatment where tumor tissue is heated to around 40 °C. Hyperthermia shows both cancer cell cytotoxicity and immune response stimulation via immune cell activation. Immunogenic responses encompass the innate and adaptive immune systems, involving the activation of macrophages, natural killer cells, dendritic cells, and T cells. Moreover, hyperthermia is commonly used in combination with different treatment modalities, such as radiotherapy and chemotherapy, for better clinical outcomes. In this review, we will focus on hyperthermia-induced immunogenic effects and molecular events to improve radiotherapy efficacy. The beneficial potential of integrating radiotherapy with hyperthermia is also discussed.

Frequent relapse and spreading of tumors during radiotherapy are principal obstacles to treatment of non-small cell lung cancer (NSCLC). In this study, we aimed to investigate how macrophage migration inhibitory factor (MIF) which is expressed at high levels in metastatic and primary lung cancer cells could regulate NSCLC metastasis in response to ionizing radiation (IR). The results indicated that MIF and ribosomal protein S3 (rpS3) were shown to be connected to inflammation, proliferation, and metastasis of NSCLC via IR-induced activation of the NF-κB pathway. Under unirradiated conditions, MIF physically established a complex with rpS3. MIF-rpS3 dissociation induced by IR activated NF-κB and made the expression of target genes of this factor transactivated in two NSCLC cell lines, A549, and NCI-H358. We also found that IR-induced dissociation of this complex led to increased secretion of pro-inflammatory cytokines and modulated the expression of epithelial-mesenchymal transition marker proteins. Finally, the effects of IR-induced dissociation of the MIF-rpS3 complex on tumor metastasis were confirmed by in vivo xenograft studies. Taken together, the present study revealed that dissociation of the MIF-rpS3 complex and subsequent activation of NF-κB is a critical post-IR exposure event that accounts for IR-induced metastatic conversion of NSCLC.

The restrictive spirometric pattern is associated with metabolic syndrome, and sarcopenia may contribute to the risk of metabolic syndrome in male patients with COPD.