Tumor cells able to recapitulate tumor heterogeneity have been tracked, isolated and characterized in different tumor types, and are commonly named Cancer Stem Cells or Cancer Initiating Cells (CSC/CIC). CSC/CIC are disseminated in the tumor mass and are resistant to anti-cancer therapies and adverse conditions. They are able to divide into another stem cell and a “proliferating” cancer cell. They appear to be responsible for disease recurrence and metastatic dissemination even after apparent eradication of the primary tumor. The modulation of CSC/CIC activities by the tumor microenvironment (TUMIC) is still poorly known. CSC/CIC may mutually interact with the TUMIC in a special and unique manner depending on the TUMIC cells or proteins encountered. The TUMIC consists of extracellular matrix components as well as cellular players among which endothelial, stromal and immune cells, providing and responding to signals to/from the CSC/CIC. This interplay can contribute to the mechanisms through which CSC/CIC may reside in a dormant state in a tissue for years, later giving rise to tumor recurrence or metastasis in patients. Different TUMIC components, including the connective tissue, can differentially activate CIC/CSC in different areas of a tumor and contribute to the generation of cancer heterogeneity. Here, we review possible networking activities between the different components of the tumor microenvironment and CSC/CIC, with a focus on its role in tumor heterogeneity and progression. We also summarize novel therapeutic options that could target both CSC/CIC and the microenvironment to elude resistance mechanisms activated by CSC/CIC, responsible for disease recurrence and metastases.

No abstract

In this population with symptomatic persistent AF and LA enlargement, septal E/e' ratio ≥11 and AF duration >90 days predicted AF recurrence at 3 months.

Nodular hepatocellular carcinoma (HCC) is characterized by the presence of a pseudocapsule (constructed usually from connective fibrous tissue) that appears hypointense on T1- and T2-weighted spin-echo (SE) and gradient-echo (GE) MR imaging sequences without a contrast medium. The presence of vascular structures inside the tumor, which are verified by histological exam, affects enhancement of the PC after administrating the contrast medium: The impregnation is more evident in the dynamic study but also persists on the delayed T1-weighted SE images. The accuracy of MR in detecting the pseudocapsule of HCC and contrast enhancement of the pseudocapsule during dynamic studies were evaluated and related to pathological findings. Thirty-seven HCC were examined in 33 patients and afterwards resected. In capsulated nodules, besides usual hematoxylin, eosin, and trichrome stainings, histochemical and immunohistochemical methods were performed. On a 1.5-T MR unit, T1- and T2-weighted SE and GE FLASH 2D sequences after intravenous injection of Gd-DTPA (dynamic study) were used. In a later phase, T1-weighted SE sequences were repeated. Histologically, the pseudocapsule (thickness 0.2-6 mm) was present in 26 of 37 nodules (70%). The dynamic study was the most suitable technique to show the pseudocapsule, which was recognized in 80.7% (21 of 26 nodules). In 5 of 26 cases, the pseudocapsule, not demonstrated by MR, was thinner than 0.4 mm. In 16 of 21 cases, in the early portal phase (30-60 s), the pseudocapsule had an early enhancement, which was more evident later; in 5 of 21 cases the enhancement was observed only in the late portal phase (1-2 min). At histological examination, 14 of 16 pseudocapsules with early enhancement showed a more prominent vasculature than those with enhancement in the equilibrium phase. Magnetic resonance was a reliable tool in demonstrating the pseudocapsule of HCC. The histological examination demonstrated a good correlation between the enhancement behavior and the vessel number of the pseudocapsule.