Influence of Organic Impurities on Fractional Crystallization of NaCl and Na2SO4 from High-Salinity Coal Chemical Wastewater: Thermodynamics and Nucleation Kinetics Analysis.

It is a valid path to realize the zero discharge of coal chemical wastewater by using the fractional crystallization method to recycle the miscellaneous salt in high-salinity wastewater. In this study, the thermodynamics and nucleation kinetics of sodium chloride (NaCl) and sodium sulfate (Na2SO4) crystallization in coal chemical wastewater were systematically studied. Through analyses of solubility, metastable zone width, and induction period, it was found that the impurity dimethoxymethane would increase the solid-liquid interface energy and critical crystal size during the nucleation of Na2SO4. Ternary phase diagrams of the pseudo-ternary Na2SO4-NaCl-H2O systems in simulated wastewater were plotted in the temperature range of 303.15 to 333.15 K, indicating that a co-ionization effect existed between NaCl and Na2SO4, and NaCl had a strong salting out effect on Na2SO4. Finally, the nucleation rate and growth rate of Na2SO4 crystals under simulated wastewater conditions were determined by the intermittent dynamic method, and the crystallization kinetic models of Na2SO4 were established. The crystallization nucleation of Na2SO4 crystals was found to be secondary nucleation controlled by surface reactions. The basic theoretical research of crystallization in this study is expected to fundamentally promote the application of fractional crystallization to realize the resource utilization of high-salinity wastewater in the coal chemical industry.

Efficient electrochemical degradation of ceftazidime by Ti3+ self-doping TiO2 nanotube-based Sb-SnO2 nanoflowers as an intermediate layer on a modified PbO2 electrode.

Ceftazidime (CAZ) is an emerging organic pollutant with a long-lasting presence in the environment. Although some PbO2 materials exhibit degradation capabilities, inefficient electron transport in the substrate layer and the problem of electrode stability still limit their use. Here, an interfacial design in which TiO2 nanotube arrays generate Ti3+ self-doping oxide substrate layers and highly active 3D Sb-SnO2 nanoflowers-like interlayers was used to prepare PbO2 anodes for efficient degradation of CAZ. Interestingly, after implementing Ti3+ self-doping in the PbO2 anode base layer and introducing 3D nanoflowers-like structures, the capacity for •OH generation increased significantly. The modified electrode exhibited 5-fold greater •OH generation capacity compared to the unmodified electrode, and a 2.7-fold longer accelerated electrode lifetime. The results indicate that interfacial engineering of the base and intermediate layers of the electrodes can improve the electron transfer efficiency, promote the formation of •OH, and extend the anode lifetime of the activated CAZ system.

Reticulated Polyamide Thin-Film Nanocomposite Membranes Incorporated with 2D Boron Nitride Nanosheets for High-Performance Nanofiltration.

Nanofiltration (NF) technology has been widely used in saline wastewater treatment due to its unique separation mechanism. However, the NF membrane, as the core of the nanofiltration technology, is restricted by the trade-off between permeability and selectivity, which greatly restricts the development of NF membranes. The interlamellar arrangement of 2D boron nitride nanosheets (BNNSs) can provide additional transport channels and selectivity, as well as strong adsorption capacity due to its high specific surface area, exhibiting significant potential for advanced membranes. In this work, BNNSs prepared by tannic acid (TA)-assisted exfoliation (TA@BNNSs) were successfully adopted to fabricate thin-film nanocomposite (TFN) membranes via interfacial polymerization (IP). The resultant TFN membranes' structure and properties were systematically characterized via various methods. The results demonstrated that the surface morphology of polyamide membranes evolved gradually from a nodular structure to a reticular topography, accompanied by the decrease of the thickness of the polyamide selective layer when incorporating TA@BNNSs into the membranes. This phenomenon can be mainly ascribed to that the uptake density and diffusion of piperazine (PIP) monomer were effectively regulated by BNNSs. This is validated by molecular dynamics and revealed by the adsorption of PIP in BN models, the diffusion coefficients, and interaction energies, respectively. In addition, the TFN membranes demonstrated improved permeance and stable solute rejection for the inorganic salts. Specifically, the water flux of PA-TA@BNNSs-10%/PMIA membrane could reach up to 109.1 ± 2.49 L·m-2·h-1 while keeping a high rejection of 97.5 ± 0.38% to Na2SO4, which was superior to most of the reported membranes in the literature. Besides, the PA-TA@BNNSs-10%/PMIA membrane exhibited an excellent stability in the long-term filtration process. The finding in this work provides a potential strategy for developing the next-generation 2D material-based membranes with high-performance for separation applications.

Simultaneous recycling of Si and Ti from diamond wire saw silicon powder and Ti-bearing blast furnace slag via reduction smelting: An investigation of the effects of refractories on recycling.

The industrial wastes diamond wire saw silicon powder (DWSSP) and Ti-bearing blast furnace slag (TBFS) are important Si and Ti secondary resources, respectively. During the industrial application of recycling DWSSP and TBFS via reduction smelting, the refractories can dissolve into the molten slag, which can change the composition of the slag and influence the extraction of Si and Ti. Unfortunately, few studies on the reduction smelting of DWSSP and TBFS related to refractories have been reported, making such studies urgently needed. Therefore, the main purpose of this work was to reveal the dissolution mechanism of refractories (alumina and magnesia bricks) and the effect of refractory dissolution on Si-Ti alloy preparation. The results show that during the reduction smelting, the dissolution of alumina and magnesia bricks changed from direct dissolution into the molten slag to indirect dissolution, and the amount of magnesia bricks dissolved was less than that of aluminum bricks. Al3+ (aluminum brick) entering the slag could replace Si4+ in [SinO2n] to form [AlxSin-xO2n]x-, increasing the viscosity of the slag. The O2- (magnesia brick) entering the slag could dissociate [AlxSin-xO2n]x-, decreasing the viscosity of the slag. Therefore, compared with alumina bricks, magnesia bricks can promote slag-alloy separation and improve the extraction ratios of Ti and Si. In the case of magnesia bricks, the maximum reduction ratio of TiO2 was 98.4 %, and the maximum extraction ratio of Si was 95.8 %. This work provides essential experimental data for the Si-Ti alloys prepared via recycling DWSSP and TBFS.

A novel approach for simultaneous recycling of Ti-bearing blast furnace slag, diamond wire saw Si powder, and Al alloy scrap for preparing TiSi2 and Al-Si alloys.

Large amounts of Ti-bearing blast furnace slag (TBFS), diamond wire saw Si powder (DWSSP), and Al alloy scrap (AAS) are generated annually. Although these are industrial waste, they contain valuable Ti, Si, and Al resources. In this work, a novel process is developed for the simultaneous recycling of Ti, Si, and Al from these three wastes to prepare TiSi2 and Al-Si alloys. TBFS, DWSSP, and CaO (flux) were mixed to form a mixed Ti-Si-slag, which was combined with AAS and underwent reduction smelting at 1823 K to prepare Si-Ti-Al alloys. Subsequently, TiSi2 (98.7%) and low-Fe Al-Si (0.64 wt% Fe) alloys were prepared sequentially by separating the molten Si-Ti-Al melt via electromagnetic directional crystallization with a pull-down rate of 3 µm/s. The impurities in the Si-Ti-Al alloy were removed during the separation process by segregation at the boundary of the solid-liquid phase and volatilization. Furthermore, the entire process produces no waste acid or waste gas. Therefore, this work has introduced an efficient and environmentally friendly method for the value-added recycling of Ti, Si, and Al resources from accumulated TBFS, DWSSP, and AAS.

Minimization and stabilization of smelting arsenic-containing hazardous wastewater and solid waste using strategy for stepwise phase-controlled and thermal-doped copper slags.

Minimization and stabilization of arsenic-containing smelting wastewater and residue is of crucial issue to resolve the arsenic contamination. Calcium arsenate is a typical precipitate produced from disposal of smelting acid wastewater. However, it suffers from poor stability and large quantity in the aqueous environment. Copper slags, as for rich-iron species materials, are disposed of in landfills or open-air tailing ponds, which are another waste material that have not been effectively utilized for reuse application. In this study, strategy for sequence of phase-controlled and thermal-doped copper slag technique was used as the efficient means of minimization and stabilization of arsenic-bearing resides. Detailed results were showed that stepwise phase precipitation significantly reduced the formation of hazardous solid waste; the total solid waste was reduced 47.0 wt% because the gypsum was separated from arsenic calcium residues through two-step methods. Subsequently, solid waste stabilization was achieved by using thermal-doped slag, and the high yield of magnetite (75.6 wt%) and fayalite (22.7 wt%) was produced from copper slags. It was proved that these iron-rich species displayed the remarkable performance to stabilize arsenic due to the formation of Fe-As-Ca-O complex; compared with the raw solid waste, the arsenic leachability was decreased from 280.75 to 1.05 mg/L via copper slag stabilization process. The immobilized arsenic content was 25.0 wt%. Overall, the proposed strategy for stepwise phase-controlled and thermal-doped copper slags was a potentially effective strategy for reducing emissions and pollution of arsenic-containing wastewater and residue.

Copper-catalyzed cross-coupling and sequential allene-mediated cyclization for the synthesis of 1,2,3-triazolo[1,5-a]quinolines.

In this paper, a tandem reaction involving copper-catalyzed cross-coupling and allene-mediated cyclization of 1-(2-ethynylaryl)-1,4-disubstituted-1,2,3-triazole with N-tosylhydrazone has been developed. This method features operational simplicity, excellent functional group compatibility, broad substrate scope, and easily available feedstock, providing an efficient and practical strategy for the synthesis of highly functionalized 1,2,3-triazolo[1,5-a]quinolines.

Cytoplasmic expression of nucleophosmin 1 as a marker for diagnosing residual disease of acute myeloid leukemia.

Nucleophosmin 1 (NPM1) is a nuclear protein and in approximately 50% to 60% of cytogenetically normal acute myeloid leukemia (AML), NPM1 is mutated and localized in the cytoplasm. Both wild type and mutant NPM1 can be detected by immunohistochemistry (IHC). We set out to evaluate whether subcellular localization of NPM1, as detected by IHC, is stable during disease course in AML, and whether cytoplasmic expression of NPM1 (NPMc+) can be used to differentiate recovery versus residual disease in formalin-fixed and hydrochloric acid/EDTA decalcified specimens. IHC against NPM1 was performed on bone marrow biopsies of 31 patients with AML at initial diagnosis and on 40 follow-up biopsies. Immunostaining patterns of NPM1, defined as NPMc+, NPMc-, and indeterminate, were correlated with morphology, ancillary tests, and clinical follow-up information. Of the 20 (64.5%) cases with NPMc- at initial diagnosis, none of the 27 follow-up biopsies showed NPMc+, regardless of disease status. Of the 11 cases (35.5%) with NPMc+ at initial diagnosis, all of the 3 biopsies with persistent/relapsed disease, and none of the 7 benign biopsies had NPMc+ at follow-up. For the 3 biopsies with indeterminate follow-up pathologic diagnoses of recovery versus residual disease, all were NPMc- at follow-up, which was consistent with remission and was supported by clinical follow-up. Therefore, subcellular localization of NPM1 as detected by IHC is stable during the course of the disease, and NPMc+ at follow-up supports residual disease in cases with NPMc+ at initial diagnosis.

Increased circulating myostatin in patients with type 2 diabetes mellitus.

The changes of plasma myostatin levels in patients with type 2 diabetes mellitus (T2D) and their clinical correlation were investigated. We recruited 43 T2D patients and 20 age-matched healthy subjects. Plasma myostatin, lipid and glucose, and serum insulin were determined. T2D patients showed significantly higher fasting plasma glucose (FPG), serum insulin and triglyceride levels, and lower high-density lipoprotein levels than normal control subjects (P<0.01). Mean plasma myostatin level in T2D patients and health controls was (66.5±17.8) and (46.2±13.8) ng/mL, respectively. An unpaired t test showed that the increase of myostatin in the T2D patients was significant (P<0.001). In both healthy control and T2D groups, the female subjects showed higher myostatin levels than the male subjects. In the T2D patients, plasma level of myostatin was negatively correlated with body mass index (BMI, r=-0.42, P<0.01) and FPG (r=-0.51, P[Symbol: see text]0.01), but positively correlated with insulin resistance index (HOMA-IR, r=0.48, P<0.01). Up-regulation of plasma myostatin in the T2D patients and its correlation with BMI, FPG and blood insulin sensitivity suggests that plasma myostatin may be implicated in the pathogenesis of T2D and thus presented as a therapeutic target for treating the disease. Furthermore, circulating myostatin levels may be used as a biomarker for the disease.

Extracavitary KSHV-associated large B-Cell lymphoma: a distinct entity or a subtype of primary effusion lymphoma? Study of 9 cases and review of an additional 43 cases.

Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma in HIV patients, which typically presents with lymphomatous effusions in the body cavities without forming mass lesions. PEL is associated with Kaposi sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus-8) with distinct clinical and pathologic features. Rare cases of KSHV-associated large B-cell lymphoma (KSHV-LBL) have been observed in the lymph nodes or extranodal sites without lymphomatous effusions during the course of disease. KSHV-LBL is generally similar to classic PEL on the basis of the clinical presentation (HIV(+) male), morphology (immunoblastic, plasmablastic, or anaplastic), immunophenotype (CD45(+), CD20(-), CD79a(-), CD30(+), CD138(+), and EMA(+)), presence of Epstein-Barr virus infection, and clonal immunoglobulin gene rearrangements. However, it is not clear whether KSHV-LBL is a distinct entity or represents part of the spectrum of classic PEL; in particular, there is no consensus diagnostic term for KSHV-LBL. In this study, we investigated the clinicopathologic features of 9 cases of KSHV-LBL from our files. An additional 43 such cases and 84 cases of classic PEL from the English literature were reviewed and compared with each other. In contrast to the classic PEL, KSHV-LBL had a very significant lower expression of CD45 (74% vs. 94%, P=0.004) but significant higher expression of CD20 (17% vs. 5%, P=0.04) and CD138 (70% vs. 38%, P=0.05). KSHV-LBL also had slightly higher positivity of CD79a (23% vs. 5%, P=0.13) and immunoglobulin light chain expression, although the difference was not statistically significant [κ chain (12% vs. 0%) and λ chain (31% vs. 21%)]. The expressions of EMA and CD30 were slightly lower in KSHV-LBL compared with those observed in PEL (57% vs. 75% and 63% vs. 76%, respectively). Interestingly, 29% (10/34) of cases of KSHV-LBL revealed aberrant CD3 expression, which may mislead to a diagnosis of T-cell lymphoma, particularly anaplastic large cell lymphoma in combination with the anaplastic morphology and expression of CD30 and EMA. Although KSHV-LBL shows different clinical presentations and some variations in immunophenotype from classic PEL, it is still uncertain, on the basis of our findings, whether it is justifiable to separate them as 2 distinct entities. Nevertheless, we feel it is necessary to have a consensus diagnostic term, and we recommend a tentative one as "KSHV-associated large B-cell lymphoma (KSHV-LBL)" to replace many different names previously used.

Expression of AIF and HtrA2/Omi in small lymphocytic lymphoma and diffuse large B-cell lymphoma.

CONTEXT: The pathogenesis of non-Hodgkin lymphoma may involve deregulation of apoptosis. In response to apoptotic stimuli, several proapoptotic proteins are released into the cytoplasm from the mitochondria, including second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein binding protein with low p I (Smac/DIABLO), apoptosis-inducing factor (AIF), and high temperature requirement protein A2 (HtrA2/Omi). Apoptosis-inducing factor promotes apoptosis through a caspase-independent pathway, while Smac/DIABLO and HtrA2/Omi do so through both caspase-dependent and caspase-independent pathways. Smac/DIABLO was reported to be strongly positive in diffuse large B-cell lymphoma (DLBCL) and virtually absent in small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). Little is known about the expression of AIF and HtrA2/Omi in lymphomas. OBJECTIVE: To evaluate the expression of AIF and HtrA2/Omi in SLL and DLBCL. DESIGN: Twenty-three DLBCLs, 20 SLLs/CLLs, and 10 benign lymph nodes were evaluated for AIF and HtrA2/Omi expression by immunohistochemical staining. RESULTS: Apoptosis-inducing factor was strongly and diffusely expressed in 19 of 23 (83%) cases of DLBCL with comparable expression pattern between germinal center-like and non-germinal center-like subgroups. Apoptosis-inducing factor was weakly positive in 15 of 20 (75%) cases of SLL/CLL with increased intensity in pseudofollicles. In contrast, HtrA2/Omi was weakly expressed in SLL/CLL (17 of 20; 85%) and DLBCL (18 of 23; 78%). CONCLUSIONS: The different expression level and pattern of AIF and HtrA2/Omi in SLL/CLL and DLBCL may suggest different apoptotic mechanisms involved in the pathogenesis and prognosis of these diseases. HtrA2/Omi does not appear to be a major player in the regulation of apoptosis of DLBCL and SLL/CLL.

SST0001, a chemically modified heparin, inhibits myeloma growth and angiogenesis via disruption of the heparanase/syndecan-1 axis.

PURPOSE: Heparanase promotes myeloma growth, dissemination, and angiogenesis through modulation of the tumor microenvironment, thus highlighting the potential of therapeutically targeting this enzyme. SST0001, a nonanticoagulant heparin with antiheparanase activity, was examined for its inhibition of myeloma tumor growth in vivo and for its mechanism of action. EXPERIMENTAL DESIGN: The ability of SST0001 to inhibit growth of myeloma tumors was assessed using multiple animal models and a diverse panel of human and murine myeloma cell lines. To investigate the mechanism of action of SST0001, pharmacodynamic markers of angiogenesis, heparanase activity, and pathways downstream of heparanase were monitored. The potential use of SST0001 as part of a combination therapy was also evaluated in vivo. RESULTS: SST0001 effectively inhibited myeloma growth in vivo, even when confronted with an aggressively growing tumor within human bone. In addition, SST0001 treatment causes changes within tumors consistent with the compound's ability to inhibit heparanase, including downregulation of HGF, VEGF, and MMP-9 expression and suppressed angiogenesis. SST0001 also diminishes heparanase-induced shedding of syndecan-1, a heparan sulfate proteoglycan known to be a potent promoter of myeloma growth. SST0001 inhibited the heparanase-mediated degradation of syndecan-1 heparan sulfate chains, thus confirming the antiheparanase activity of this compound. In combination with dexamethasone, SST0001 blocked tumor growth in vivo presumably through dual targeting of the tumor and its microenvironment. CONCLUSIONS: These results provide mechanistic insight into the antitumor action of SST0001 and validate its use as a novel therapeutic tool for treating multiple myeloma.

Heparanase plays a dual role in driving hepatocyte growth factor (HGF) signaling by enhancing HGF expression and activity.

Hepatocyte growth factor (HGF) is a heparin-binding cytokine that enhances growth, motility, and angiogenesis of many tumor types, including multiple myeloma where it is often highly expressed. However, little is known regarding what controls HGF level and activity in these tumors. Evaluation of bone marrow biopsies from myeloma patients revealed a strong positive correlation between the levels of HGF and heparanase, an endoglucuronidase known to promote aggressive tumor behavior. In vitro, addition of recombinant heparanase to myeloma cells or transfection of myeloma cell lines with the cDNA for heparanase significantly increased tumor cell expression and secretion of biologically active HGF. Shed syndecan-1, whose levels in myeloma are also enhanced by heparanase expression, binds to secreted HGF. This syndecan-1-HGF complex is active as shown by its ability to stimulate paracrine signaling via c-Met, the cell surface receptor for HGF. Surprisingly, heparanase enzyme activity was not required for up-regulation of HGF expression by the tumor cells. This is in contrast to the heparanase-mediated enhanced syndecan-1 shedding, which does require activity of the enzyme. This suggests that two different functional domains within the heparanase enzyme (the enzyme active site and a separate site) contribute to events leading to enhanced HGF signaling. These findings demonstrate a novel mechanism driving the HGF pathway whereby heparanase stimulates an increase in both HGF expression and syndecan-1 shedding to enhance HGF signaling. This work also provides further mechanistic insight into the dynamic role of heparanase in driving aggressive tumor progression.

Multiple hemodynamic effects of endogenous hydrogen sulfide on central nervous system in rats.

BACKGROUND: Endogenous hydrogen sulfide is a new neuromodulator which takes part in the regulation of central nervous system physiology and diseases. Whether endogenous hydrogen sulfide in the central nervous system regulates cardiovascular activity is not known. In the present study, we observed the hemodynamic changes of hydrogen sulfide or its precursor by intracerebroventricular injection, and investigate the possible roles of endogenous digitalis like factors and sympathetic activity in the regulation. METHODS: Ninety-four Sprague-Dawley rats underwent a right cerebroventricular puncture, then the hydrogen sulfide saturation buffer or its precursor injected by intrcerebroventricular catheter. A heperin-filled catheter was inserted into the right femoral artery or into the left ventricle, and changes of blood pressure or cardiac function recorded by a Powerlab/4S instrument. Phentolamine or metoprolol were pre-injected to observe the possible role in autonomic nerve activity. After rats were sacrificed, plasma was collected and endogenous digitalis-like factors were measured with a commercial radioimmunoassay kit. The aortic, cardiac sarcolemmal vesicles were isolated and the activity of Na(+)-K(+)-ATPase was measured as ouabain-sensitive ATP hydrolysis under maximal velocity conditions by measuring the release of inorganic phosphate from ATP. Unpaired Student's t test for two groups or analysis of variances (ANOVA) for multiple groups were used to compare the differences of the changes. RESULTS: Intracerebroventricular injection of hydrogen sulfide induced a transient hypotension, then dramatic hypertenive effects in a dose-dependent manner. Bolus injection of L-cysteine or beta- mercaptopyruvate also increased mean arterial pressure (P < 0.01), whereas hydroxylamine-a cystathionine beta synthase inhibitor decreased the arterial pressure (P < 0.01). Hydrogen sulfide and L-cysteine increased mean arterial pressure, left ventricular develop pressure and left-ventricle maximal rate of systolic and diastolic pressure; these functions were decreased by hydroxylamine (P < 0.01). Glibenclamide (a K(ATP) channel blocker) blocked the transient hypotensive effect, phentolamine (an alpha-adrenergic receptor blocker) blocked the hypertensive effect, and metoprolol (a selective beta 1 receptor blocker) blocked the positive inoptropic effect of central nervous system hydrogen sulfide. The endogenous digitalis-like factors in plasma were elevated (P < 0.01) after treatment with L-cysteine, association with decreasing Na(+)-K(+)-ATPase activity in cardiac or aortic sarcolemmal vesicles (P < 0.01). Hydroxylamine injection reduced the endogenous digitalis-like factors level in plasma association with increasing Na(+)-K(+)-ATPase activity in cardiac and aortic sarcolemmal vesicles. CONCLUSION: Central nervous system endogenous hydrogen sulfide upregulated mean arterial pressure and cardiac systolic function by activation of sympathetic nerves or release of endogenous digitalis-like factors.

Heparanase enhances local and systemic osteolysis in multiple myeloma by upregulating the expression and secretion of RANKL.

Excessive bone destruction is a major cause of morbidity in myeloma patients. However, the biological mechanisms involved in the pathogenesis of myeloma-induced bone disease are not fully understood. Heparanase, an enzyme that cleaves the heparan sulfate chains of proteoglycans, is upregulated in a variety of human tumors, including multiple myeloma. We previously showed that heparanase promotes robust myeloma tumor growth and supports spontaneous metastasis of tumor cells to bone. In the present study, we show, for the first time, that the expression of heparanase by myeloma tumor cells remarkably enhances bone destruction locally within the tumor microenvironment. In addition, enhanced heparanase expression in the primary tumor also stimulated systemic osteoclastogenesis and osteolysis, thus mimicking the systemic osteoporosis often seen in myeloma patients. These effects occur, at least in part, as the result of a significant elevation in the expression and secretion of receptor activator of NF-κB ligand (RANKL) by heparanase-expressing myeloma cells. Moreover, analysis of bone marrow biopsies from myeloma patients reveals a positive correlation between the level of expression of heparanase and RANKL. Together, these discoveries reveal a novel and key role for heparanase in promoting tumor osteolysis and show that RANKL is central to the mechanism of heparanase-mediated osteolysis in myeloma.

Dual effects of TGF-beta on ERalpha-mediated estrogenic transcriptional activity in breast cancer.

BACKGROUND: TGF-beta resistance often develops in breast cancer cells that in turn overproduce this cytokine to create a local immunosuppressive environment that fosters tumor growth and exacerbates the invasive and metastatic behavior of the tumor cells themselves. Smads-mediated cross-talk with the estrogen receptor has been implied to play an important role in development and/or progression of breast cancer. We investigated how TGF-beta regulates ERalpha-induced gene transcription and potential mechanisms of frequent TGF-beta resistance in breast cancer. METHODS: Effect of TGF-beta on ERalpha-mediated gene transcription was investigated in breast cancer cell lines using transient transfection, real-time PCR, sequential DNA precipitation, and small interfering RNA assays. The expression of Smads on both human breast cancer cell lines and ERalpha-positive human breast cancer tissue was evaluated by immunofluorescence and immunohistochemical assays. RESULTS: A complex of Smad3/4 mediates TGF-beta inhibition of ERalpha-mediated estrogenic activity of gene transcription in breast cancer cells, and Smad4 is essential and sufficient for such repression. Either overexpression of Smad3 or inhibition of Smad4 leads to the "switch" of TGF-beta from a repressor to an activator. Down-regulation and abnormal cellular distribution of Smad4 were associated with some ERalpha-positive infiltrating human breast carcinoma. There appears a dynamic change of Smad4 expression from benign breast ductal tissue to infiltrating ductal carcinoma. CONCLUSION: These results suggest that aberrant expression of Smad4 or disruption of Smad4 activity lead to the loss of TGF-beta suppression of ERalpha transactivity in breast cancer cells.

Unusual expression of CD94 on CD8+ TCR-alpha beta T cells in infectious mononucleosis.

Infectious mononucleosis, caused by primary Epstein-Barr virus (EBV) infection, is usually a benign, self-limited lymphoproliferative disorder. We report a case of a 21-year-old woman who presented with fever, sore throat, severe neutropenia, and absolute lymphocytosis with atypical lymphocytes. In situ hybridization for EBV-encoded small RNA performed on the marrow aspirate clot specimen demonstrated scattered positive cells. EBV serology was compatible with primary infection. Flow cytometry immunophenotypic studies performed on aspirate material revealed a profoundly expanded population of CD8+ T-cell receptor (TCR)-alphabeta T cells with uniform expression of CD94. No evidence of a monoclonal T-cell population was found as assessed by V(beta) use with flow cytometry and by TCR gamma-chain gene rearrangement using a polymerase chain reaction method. Uniform expression of CD94 in an exuberant reactive proliferation of CD8+ TCR-alphabeta T cells in infectious mononucleosis has not been reported previously, and combined with atypical morphology might be misinterpreted as a malignant neoplasm.

Expression of inhibitor of apoptosis proteins in B-cell non-Hodgkin and Hodgkin lymphomas.

BACKGROUND: Inhibitor of apoptosis proteins (IAPs) inhibit apoptosis by binding specific caspases, and possibly by other mechanisms. Eight IAPs have been identified in humans, of which cIAP1, cIAP2, and XIAP are well known. IAPs are being investigated as potential treatment targets in cancer patients. METHODS: cIAP1, cIAP2, and XIAP were assessed in lymphoma cell lines, 240 B-cell non-Hodgkin lymphoma (NHL) tumors, and 40 Hodgkin lymphoma (HL) tumors. RESULTS: All IAPs were expressed in most NHL and all HL cell lines. In NHL tumors, cIAP1 was expressed in 174 (73%), cIAP2 in 115 (48%), and XIAP in 37 (15%). cIAP1 was positive in all precursor B-cell lymphoblastic lymphoma/leukemia (LBL) and nodal marginal zone B-cell lymphoma (MZL), over 90% of follicular lymphoma and diffuse large B-cell lymphoma (DLBCL), and approximately 50% to 60% of myeloma, Burkitt lymphoma (BL), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM), small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL), extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT-lymphoma), splenic MZL, and mantle cell lymphoma. cIAP2 was positive in all MALT-lymphoma, over 90% of precursor B-cell LBL (94%), most BL (75%), LPL/WM (71%), and SLL/CLL (67%), and approximately 40% to 60% of follicular lymphoma, myeloma, and DLBCL. XIAP was positive most cases of precursor B-cell LBL (57%) and approximately 30% to 40% of nodal MZL, BL, and DLBCL. In HL tumors, cIAP1 was positive in 30 (75%), cIAP2 in 27 (68%), and XIAP in 23 (58%), and did not correlate with histologic type. CONCLUSIONS: Differential expression of IAPs in B-cell lymphomas suggests differences in pathogenesis that may have implications for novel treatment strategies targeting IAPs.

Expression of Smac/DIABLO in B-cell non-Hodgkin and Hodgkin lymphomas.

Inhibitor of apoptosis proteins (IAPs) are upregulated in cancers and suppress cell death, in part, through their ability to directly inhibit caspases. Inhibitor of apoptosis proteins are differentially expressed in B-cell lymphomas. The functions of some IAPs are counteracted by the cell death inducer, second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO). In this study, we investigated the expression levels of Smac/DIABLO in 14 lymphoma cell lines by Western blot analysis. We also assessed 247 B-cell non-Hodgkin's lymphoma (NHL) and 40 Hodgkin's lymphoma (HL) tumors using immunohistochemical methods. Smac/DIABLO was expressed in most NHL and all HL cell lines. In NHL, Smac/DIABLO was expressed in 117 (47%) tumors and was differentially expressed in various NHL types. In most NHLs, from 29% to 68% of tumors were positive; however, Smac/DIABLO was not detected in small lymphocytic lymphoma/chronic lymphocytic leukemia and Burkitt lymphoma, and was rare in extranodal marginal zone B-cell lymphoma. In HL, Smac/DIABLO was positive in 25 (63%) tumors. Unlike NHL, all types of HL were positive for Smac/DIABLO, although nodular sclerosis was least often positive. The differential expression of Smac/DIABLO in NHLs suggests that apoptotic mechanisms are differentially involved in their pathogenesis. These results may also have implications for using Smac/DIABLO or its agonists as therapeutic agents.