Hybrid tumours of the salivary glands. A report of two cases involving the palate and a review of the literature

Hybrid tumours are very rare salivary gland lesions composed of two or more different tumoural entities in a single neoplasm that arise within a definite topographical region. In most cases adenoid cystic carcinoma has been the predominant component in these lesions. In this study we describe two patients with hybrid tumours located in the palate, one in a 49-year-old woman and one in a 71-year-old man. The first case involved adenoid cystic carcinoma and mucoepidermoid carcinoma, and the patient in the second case exhibited adenoid cystic carcinoma and epithelial-myoepithelial carcinoma. Both patients were treated with surgery and radiotherapy, and there has been no evidence of recurrence after 13 and 36 months of follow-up, respectively. The recognition of the histologic component with the higher grade of malignancy in every case of hybrid tumour of the salivary glands is a necessary step to determine the biological behaviour and, consequently, to determine the proper therapeutic approach.     

A natural musaceas plant extract inhibits proteasome activity and induces apoptosis selectively in human tumor and transformed, but not normal and non-transformed, cells

Animal studies have demonstrated that a dietary polyphenol known as tannic acid (TA) exhibits anticarcinogenic activity in chemically induced cancers. Most recently, we have reported that TA and ester-bond containing green tea polyphenols are potent proteasome inhibitors in vitro and in vivo. We hypothesize that CellQuest, a patented formula which contains high level of TA obtained from a musaceas (plantain) plant extract, will inhibit the tumor cell proteasome activity. Here, we report that a partially purified CellQuest fraction, S3, potently inhibits the proteasomal chymotrypsin-like activity of Jurkat T cell extracts in a concentration-dependent manner. Inhibition of the proteasome by S3 in leukemia Jurkat T, simian virus 40-transformed and prostate cancer LNCaP cells results in accumulation of ubiquitinated proteins and the natural proteasome substrate p27Kip1, followed by induction of apoptosis. In contrast, non-transformed, immortalized human natural killer cells and normal human fibroblasts are resistant to S3-mediated proteasome inhibition and apoptosis induction. Our present study suggests that CellQuest targets and inhibits the proteasome selectively in tumor cells, which may contribute to the claimed anticancer activity.     

Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis-induced fibrosis

Peritoneal fibrosis is one of the most common morphological changes observed in continuous ambulatory peritoneal dialysis (CAPD) patients. Both resident fibroblasts and new fibroblast-like cells derived from the mesothelium by epithelial-to-mesenchymal transition are the main cells involved fibrogenesis. In order to establish markers of peritoneal impairment and pathogenic clues to explain the fibrogenic process, we conducted an immunohistochemical study focused on peritoneal fibroblasts. Parietal peritoneal biopsies were collected from four patient groups: normal controls (n=15), non-CAPD uremic patients (n=17), uremic patients on CAPD (n=27) and non-renal patients with inguinal hernia (n=12). To study myofibroblastic conversion of mesothelial cells, -smooth muscle actin (SMA), desmin, cytokeratins and E-cadherin were analyzed. The expression of CD34 by fibroblasts was also analyzed. Fibroblasts from controls and non-CAPD uremic patients showed expression of CD34, but no myofibroblastic or mesothelial markers. The opposite pattern was present during CAPD-related fibrosis. Expression of cytokeratins and E-cadherin by fibroblast-like cells and -SMA by mesothelial and stromal cells supports that mesothelial-to-myofibroblast transition occurs during CAPD. Loss of CD34 expression correlated with the degree of peritoneal fibrosis. The immunophenotype of fibroblasts varies during the progression of fibrosis. Myofibroblasts seem to derive from both activation of resident fibroblasts and local conversion of mesothelial cells.Manuel López-Cabrera and Rafael Selgas contributed equally to the article.     

Long-term PM2.5 exposure before diagnosis is associated with worse outcome in breast cancer

Breast Cancer Research and Treatment - Many patients seek breast reconstruction following mastectomy. Debate exists regarding the best reconstructive option. The authors evaluate outcomes comparing...     

Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease

Background and Objective High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease. Patients and Measurements We studied 82 dialysis patients treated by PD (n = 44, 23 males and 21 females, mean age 54·4 ± 1·8 years) or HD (n = 38, 22 males and 16 females, age 60·8 ± 1·6 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of leptin, adiponectin and resistin were measured in all subjects. Information on vascular disease (cerebral vascular, peripheral vascular and heart disease) was obtained from a detailed medical history. Results PD patients showed significantly higher serum leptin concentrations [median (interquartile range), 28·7 (13·0–71·9) µg/l] than those found in patients on HD [9·7 (4·7–31·9) µg/l, P < 0·01] or in conservative management [5·9 (4·3–38·6) µg/l, P < 0·05]. Adiponectin concentrations were similar in the three groups of patients (mean ± SEM, 48·0 ± 4·5 mg/l in PD, 57·7 ± 4·4 mg/l in HD, and 44·4 ± 7·0 mg/l in controls, NS). Patients treated by both PD and HD exhibited resistin concentrations significantly higher than those found in controls (26·3 ± 0·99 and 27·5 ± 1·4 µg/l, respectively, vs. 17·3 ± 1·0 µg/l, P < 0·001). Leptin concentrations were positively correlated with body mass index (BMI) (r = 0·287, P < 0·01) and adiponectin levels were negatively related to BMI (r = ?0·416, P < 0·001) and the homeostatic model assessment (HOMA‐R) index (r =?0·216, P < 0·05). Leptin, adiponectin and resistin levels in patients with previous vascular events were similar to those found in patients without these complications. Logistic regression analysis did not demonstrate any relationship between serum adipocytokine concentrations and the presence of vascular disease of any type. A significant relationship between resistin and heart disease [odds ratio (OR) 1·80 (1·03–3·15), P = 0·039] was found when analysing subgroups of patients. Conclusions These data suggest that leptin levels are higher in PD patients, and resistin levels are higher in PD and HD patients in relation to patients on conservative management, whereas adiponectin concentrations are similar in the three groups. These results do not support the presence of a clinically relevant relationship between adipocytokines and previous episodes of vascular disease in the whole population or in patients classified in subgroups, with the only exception of a relationship between resistin levels and heart disease.     

Trypanosoma cruzi nucleoside triphosphate diphosphohydrolase 1 (TcNTPDase-1) biochemical characterization,immunolocalization and possible role in host cell adhesion

Previous work has suggested that Trypanosoma cruzi diphosphohydrolase 1 (TcNTPDase-1) may be involved in the infection of mammalian cells and serve as a potential target for rational drug design. In this work, we produced recombinant TcNTPDase-1 and evaluated its nucleotidase activity, cellular localization and role in parasite adhesion to mammalian host cells. TcNTPDase-1 was able to utilize a broad range of triphosphate and diphosphate nucleosides. The enzyme's K_m for ATP (0.096 mM) suggested a capability to influence the host's ATP-dependent purinergic signaling. The use of specific polyclonal antibodies allowed us to confirm the presence of TcNTPDase-1 at the surface of parasites by confocal and electron microscopy. In addition, electron microscopy revealed that TcNTPDase-1 was also found in the flagellum, flagellum insertion region, kinetoplast, nucleus and intracellular vesicles. The presence of this enzyme in the flagellum insertion region and vesicles suggests that it may have a role in nutrient acquisition, and the widespread distribution of TcNTPDase-1 within the parasite suggests that it may be involved in other biological process. Adhesion assays using anti-TcNTPDase-1 polyclonal antibodies as a blocker or purified recombinant TcNTPDase-1 as a competitor revealed that the enzyme has a role in parasite–host cell adhesion. These data open new frontiers to future studies on this specific parasite–host interaction and other unknown functions of TcNTPDase-1 related to its ubiquitous localization.     

Geomechanical behavior of the reservoir and caprock system at the In Salah CO2 storage project

Almost 4 million metric tons of CO₂ were injected at the In Salah CO₂ storage site between 2004 and 2011. Storage integrity at the site is provided by a 950-m-thick caprock that sits above the injection interval. This caprock consists of a number of low-permeability units that work together to limit vertical fluid migration. These are grouped into main caprock units, providing the primary seal, and lower caprock units, providing an additional buffer and some secondary storage capacity. Monitoring observations at the site indirectly suggest that pressure, and probably CO₂, have migrated upward into the lower portion of the caprock. Although there are no indications that the overall storage integrity has been compromised, these observations raise interesting questions about the geomechanical behavior of the system. Several hypotheses have been put forward to explain the measured pressure, seismic, and surface deformation behavior. These include fault leakage, flow through preexisting fractures, and the possibility that injection pressures induced hydraulic fractures. This work evaluates these hypotheses in light of the available data. We suggest that the simplest and most likely explanation for the observations is that a portion of the lower caprock was hydrofractured, although interaction with preexisting fractures may have played a significant role. There are no indications, however, that the overall storage complex has been compromised, and several independent data sets demonstrate that CO₂ is contained in the confinement zone.In Salah is an industrial-scale carbon capture and storage project located in central Algeria. Between 2004 and 2011, 3.8 million metric tons of CO₂ were injected into an anticlinal structure at ∼1,800 m depth. Storage integrity at the site is provided by a massive, 950-m-thick caprock that sits above the injection interval (Fig. 1). It consists of a number of low-permeability units that work together to limit vertical fluid migration. These are grouped into main caprock units, providing the primary seal, and lower caprock units, providing an additional buffer and some secondary storage capacity.Open in a separate windowFig. 1.Stratigraphic column with interval depths at well KB-502. Depth is given as meters of true vertical depth below the rotary table (m TVD brt) of the drilling rig, a common elevation datum in the oil and gas industry.In June 2011, injection operations halted at the site to allow reevaluation of the injection strategy (1). At the time, several monitoring observations suggested that pressure, and probably CO₂, had migrated vertically into the lower portion of the caprock. Although there are no indications that overall storage integrity has been compromised, these observations raise interesting questions about the geomechanical behavior of the reservoir and lower caprock system.Several hypotheses have been put forward by various groups to explain these observations. These include fault leakage, flow through preexisting fractures, or the possibility that injection pressures hydraulically fractured a portion of the lower seal (2–13). In this work, we evaluate these hypotheses in light of the available data. We suggest that the most likely explanation for the observed behavior is that the lower caprock was hydrofractured, although interaction with preexisting fractures may have played a significant role. Previous studies by Bissell and colleagues (4) and Oye and colleagues (8) have shown that injectivity and microseismic data show indications of fracturing behavior, at least in the reservoir and possibly in the overburden. Here, we use well data to constrain the state of stress in the reservoir and lower caprock, providing strong support for the hydrofracture hypothesis.This work also highlights those monitoring and analysis methods that have been most useful for understanding the field behavior, as well as lessons learned and potential improvements. This perspective can guide future carbon storage projects.     

Transdifferentiation of peripheral blood mononuclear cells into epithelial-like cells

Bone marrow-derived stem cells have the potential to transdifferentiate into unexpected peripheral cells. We hypothesize that circulating bone marrow-derived stem cells might have the capacity to transdifferentiate into epithelial-like cells and release matrix metalloproteinase-1-modulating factors such as 14-3-3varsigma for dermal fibroblasts. We have characterized a subset of peripheral blood mononuclear cells (PBMCs) that develops an epithelial-like profile. Our findings show that these cells develop epithelial-like morphology and express 14-3-3varsigma and keratin-5, -8 as early as day 7 and day 21, respectively. When compared with control, conditioned media collected from PBMCs in advanced epithelial-like differentiation (cultures on days 28, 35, and 42) increased the matrix metalloproteinase-1 expression in dermal fibroblasts (P 相似文献