This paper presents an international, multiple-code, simulation study of coupled thermal, hydrological, and mechanical (THM) processes and their effect on permeability and fluid flow in fractured rock around heated underground nuclear waste emplacement drifts. Simulations were conducted considering two types of repository settings: (a) open emplacement drifts in relatively shallow unsaturated volcanic rock, and (b) backfilled emplacement drifts in deeper saturated crystalline rock. The results showed that for the two assumed repository settings, the dominant mechanism of changes in rock permeability was thermalmechanically-induced closure (reduced aperture) of vertical fractures, caused by thermal stress resulting from repository-wide heating of the rock mass. The magnitude of thermal-mechanically-induced changes in permeability was more substantial in the case of an emplacement drift located in a relatively shallow, low-stress environment where the rock is more compliant, allowing more substantial fracture closure during thermal stressing. However, in both of the assumed repository settings in this study, the thermalmechanically induced changes in permeability caused relatively small changes in the flow field, with most changes occurring in the vicinity of the emplacement drifts.

Chemokines and their receptors regulate the trafficking of immune cells during their development, inflammation, and tissue repair. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/ stromal cell-derived factor-1 (SDF1)-3'A) in CXCL12/SDF1 gene was assessed in breast cancer, Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL), since the chemokine CXCL12, previously known as SDF1, and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis, and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using a restriction enzyme HpaII cleavage. No significant difference was observed in genotype distribution between breast cancer patients (GG: 57.3%; GA: 39.8%; AA: 2.9%) and healthy female controls (GG: 62.9%; GA: 33%; AA: 4.1%) nor between HL patients (GG: 61.1%; GA:27.8%; AA: 11.1%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%), whereas a significant difference was observed in genotype distribution between NHL patients (GG: 51.4%; GA: 47.1%; AA: 1.5%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%). Further studies will be necessary to elucidate the cancer chemokine network. However, this study suggests that CXCL12 rs1801157 polymorphism may have important implications in the pathogenesis of NHL.

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Chemokines and its receptors have significant impact on physiological and pathological processes and studies concerning their association with tumor biology are subject of great interest in scientific community. CXCL12/CXCR4 axis has been widely studied due to its significant role in tumor microenvironment, but it is also important to development and maintenance of tissues and organs, for example, in the brain and cerebellum. Studies have demonstrated that CXCL12 and CXCR4 are required for normal cerebellar development and that dysfunction in this pathway may be involved with medulloblastoma pathogenesis. In this context, a new molecular subgroup has been suggested based on the importance of the association between CXCR4 overexpression and sonic hedgehog subgroup. Treatment using CXCR4 antagonists showed significant results, evidencing the important role and possible therapeutic capacity of CXCR4 in MB. This review summarizes studies on MB cell biology, focusing on a chemokine-receptor axis, CXCL12/CXCR4, that may have implications for treatment strategies once it can improve life expectancy and reduce neurocognitive sequelae of patients with this neoplasia.Tumors originate from cells with dysregulation on normal growth mechanism control, caused by genetic mutations. 1 Studies have demonstrated that the tumor microenvironment is constituted not only by tumor cells, but also of extracellular matrix, fibroblasts, endothelial cells and immune cells that could influence tumor progression. 2,3 One chemokine that has been acquiring relevance in cancer is CXCL12, whose receptor CXCR4 is overexpressed in at least 20 different human cancers, including breast cancer, ovarian cancer, melanoma and prostate cancer. 4 Besides their critical role in tumor cell growth, 5 survival and angiogenesis in multiple cancers, 6 this chemokine receptor has been described as an important homing and metastatic mediator of secondary growth in organs that produce CXCL12, such as liver, 7 lung and bone marrow. 8 However, the contribution of CXCR4/CXCL12 axis in organ-specific dissemination and tumor growth has been strongly debated. [9][10][11] Studies have shown that CXCR4, a molecule strongly expressed in proliferating granule neuron precursors (GNP) that are cell types associated with medulloblastoma (MB), 12 is also involved with sonic hedgehog (SHH) pathway, 13 as well as its ligand, that significantly enhances SHH-induced cell proliferation. 14,15 CXCR4 is predominantly expressed in tumor areas, while CXCL12 is expressed mainly in the endothelium of tumor associated blood vessels. 16,17 It has also been described another receptor for the chemokine CXCL12, the CXCR7, however, it seems to play no role in this tumor. 15 CXCL12 and CXCR4 are expressed in several brain tumors, including MB and the expression level of this receptor appears to have prognostic significance. 16,18,19 Positive CXCR4 expression was identified in nine of ten samples of MB tumors, in contrast to little or no staining in normal cerebellum counterparts. 16 Studies als...

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