No abstract

The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma.

Plasma miRNAs provide reliable and noninvasive markers for CRC. Plasma miR-21 warrants study in larger cohorts. It seems uniquely promising as a plasma biomarker for CRC.

Plasma miRNAs are reliable, noninvasive, and inexpensive markers for CR adenomas. This miRNA panel warrants study in larger cohorts. Plasma-based assays could provide better screening compliance compared to fecal occult blood or endoscopic screening.

BACKGROUND:The number of long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasing; however, few studies have addressed their long-term pulmonary function. METHODS: The authors examined 660 baseline and follow-up pulmonary function tests in 89 long-term survivors of pediatric hematologic malignancies and allo-HSCT. RESULTS: At least 1 abnormal lung parameter was seen in 40.4% of baseline tests and developed in 64% of post-allo-HSCT tests (median follow-up: 8.9 years). Abnormal baseline values in ratio of forced expiratory volume in 1 second and forced vital capacity (FEV 1 /FVC), FEV 1 , residual volume (RV), functional residual capacity (FRC), and FVC were associated with abnormal post-allo-HSCT values. The following pulmonary function values declined significantly with time: FEV 1 /FVC, forced mid-expiratory flow (FEF 25%-75% ), total lung capacity (TLC), diffusion capacity corrected for hemoglobin (DLCO corr ), RV, FRC, and RV/TLC. Older age at the time of allo-HSCT was associated with lower FEV 1 /FVC, FEF 25%-75% , and DLCO corr and higher RV/TLC. Patients who experienced respiratory events within 1 year post-allo-HSCT had lower FEV 1 and FVC values and higher RV/TLC from their baseline pulmonary function tests. Female patients had reduced FVC, TLC, and RV values but higher FEV 1 /FVC. Pulmonary dysfunction was also associated with high-risk hematological malignancies and peripheral blood HSC product. CONCLUSIONS: Abnormal pulmonary functions in allo-HSCT survivors are prevalent, which underscore the need for risk-adapted continual monitoring and improved preventive and management strategies.