Spatio-Temporal Evolution of Sediments Pollution with Mobile Heavy Metals in an Abandoned Mining Area from Romania

The present chapter focuses on spatio-temporal evolution of sediments pollution with mobile heavy metals in five sampling campaigns, in an abandoned gold-bearing mining area from Certeju de Jos, Hunedoara County. The investigated zone is situated in a region where for a long period intense activities of mining exploitation was conducted. For determination of total metals content, sediment samples were dissolved with ultrapure nitric acid to microwave digestion. For the determination of mobile metals concentrations, it used the first step of BCR 701 sequential extraction scheme in a modified form, by reducing the extraction time from 16 hours to 20 minutes by sonication. The total and mobile concentrations of metals were determined by using ICP-MS. The concentrations of the mobile fractions of Cd, As and Cu are between 60 and 98% for Cd, 10 and 38% for As and up to 44% for Cu, indicating their presence in a bioavailable form. Due to the high mobility, these metals can pass from sediment to surface water and, implicitly, to the aquatic ecosystems. The pollution indices, calculated for the total content of As, Cd, Cu, Ni and Pb, indicate the presence of a strong environmental risk of sediment degradation in most investigated site

Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O-DLBCL), including PB-DLBCL. A total of 103 patients with O-DLBCL were included and compared with 63 (extra)nodal non-osseous (NO)-DLBCLs with germinal center B-cell phenotype (NO-DLBCL-GCB). Cell-of-origin was determined by immunohistochemistry and gene-expression profiling (GEP) using (extended)-NanoString/Lymph2Cx analysis. Mutational profiles were identified with targeted next-generation deep sequencing, including 52 B-cell lymphoma-relevant genes. O-DLBCLs, including 34 PB-DLBCLs, were predominantly classified as GCB phenotype based on immunohistochemistry (74%) and NanoString analysis (88%). Unsupervised hierarchical clustering of an extended-NanoString/Lymph2Cx revealed significantly different GEP clusters for PB-DLBCL as opposed to NO-DLBCL-GCB (P < .001). Expression levels of 23 genes of 2 different targeted GEP panels indicated a centrocyte-like phenotype for PB-DLBCL, whereas NO-DLBCL-GCB exhibited a centroblast-like constitution. PB-DLBCL had significantly more frequent mutations in four GCB-associated genes (ie, B2M, EZH2, IRF8, TNFRSF14) compared with NO-DLBCL-GCB (P = .031, P = .010, P = .047, and P = .003, respectively). PB-DLBCL, with its corresponding specific mutational profile, was significantly associated with a superior survival compared with equivalent Ann Arbor limited-stage I/II NO-DLBCL-GCB (P = .016). This study is the first to show that PB-DLBCL is characterized by a GCB phenotype, with a centrocyte-like GEP pattern and a GCB-associated mutational profile (both involved in immune surveillance) and a favorable prognosis. These novel biology-associated features provide evidence that PB-DLBCL represents a distinct extranodal DLBCL entity, and its specific mutational landscape offers potential for targeted therapies (eg, EZH2 inhibitors)

Exploring Morphologic and Molecular Aspects of Endometrial Cancer under Progesterone Treatment in the Context of Fertility Preservation

Objective The standard treatment of early-stage (FIGO [International Federation of Gynecology and Obstetrics] I) endometrioid endometrial cancer (EEC) is hysterectomy with bilateral salpingo-oophorectomy. An alternative approach for younger women with low-grade EEC who wish to preserve fertility may be hormonal treatment. Previous studies have suggested that progesterone may elicit its antitumor effect in EEC by interacting with the Wingless (Wnt) and/or phosphatidylinositol 3-kinase (PI3K)/Akt pathways. Therefore, we explored whether common activating genetic alterations in Wnt and PI3K/Akt signaling correlated with nonresponsiveness to progesterone therapy for low-grade EEC. In addition, we investigated whether benign morphology under progesterone treatment is accompanied by the absence of genetic changes. Methods We analyzed molecular alterations in the Wnt and PI3K/Akt signaling in 84 serial endometrial samples from 11 premenopausal patients with progesterone receptor-positive low-grade EEC conservatively treated with progesterone and correlated these with histological and clinical follow-up. Results There were 6 responders and 5 nonresponders to progesterone treatment. The response rate to progesterone treatment was 55%, and the relapse rate was 83%. All responders had alterations in both the Wnt and PI3K/Akt pathway before treatment. In the nonresponder group, tumors inconsistently showed alterations in none, 1, or both pathways. Normalization of the endometrium morphology under progesterone treatment is accompanied by the absence of the genetic changes found in the specimen before treatment. Conclusions We found that activating molecular alterations in either Wnt or PI3K/Akt signaling pathways did not predict resistance to progesterone treatment. It seems that morphological response goes along with disappearance of the established mutations. This exploratory study suggests that Wnt or PI3K/Akt status is unable to predict response to progesterone treatment in patients with EEC

Assessment of Integrative Therapeutic Methods for Improving the Quality of Life and Functioning in Cancer Patients—A Systematic Review

Background: Cancer rehabilitation represents a series of measures adopted for the recovery of psychological, emotional, social, and financial functioning in the case of cancer patients. The purpose of this study is to identify the main elements of therapeutic management in the field of medical rehabilitation, as well as integrative, complementary medicine and holistic approaches that can be performed on the oncological patient. Methods: This systematic literature review follows the methodology outlined in the “Preferred Reporting Items for Systematic Reviews and Meta-Analysis” (“PRISMA”) statement, which is an internationally recognized and widely accepted standard. Results: Active rehabilitative therapies offer therapeutic options for improving the functioning and quality of life of oncological patients; these therapies comprehensively address both the physical and psychological aspects of the disease. This review also includes the latest novelties and nanotechnologies applied in oncological rehabilitation, for example, drugs (or supplements) inspired by nature. Conclusions: Physical and rehabilitation medicine, mostly using stimulating therapeutic methods, was recently added to the list of contraindications in the management of oncological patients, both as an approach to the pathological concept itself and as an approach to the main clinical consequences and functional aspects of oncological therapies. Integrative, complementary medicine presents an important therapeutic resource in the case of oncological patients. Advanced studies are needed in the future to further ascertain the role of these therapies