Primary Effusion Lymphoma Cell Death Induced by Bortezomib and AG 490 Activates Dendritic Cells through CD91

To understand how cytotoxic agent-induced cancer cell death affects the immune system is of fundamental importance to stimulate immune response to counteract the high mortality due to cancer. Here we compared the immunogenicity of Primary Effusion Lymphoma (PEL) cell death induced by anticancer drug Bortezomib (Velcade) and Tyrphostin AG 490, a Janus Activated Kinase 2/signal trasducer and activator of transcription-3 (JAK2/STAT3) inhibitor. We show that both treatments were able to induce PEL apoptosis with similar kinetics and promote dendritic cells (DC) maturation. The surface expression of molecules involved in immune activation, namely calreticulin (CRT), heat shock proteins (HSP) 90 and 70 increased in dying cells. This was correlated with DC activation. We found that PEL cell death induced by Bortezomib was more effective in inducing uptake by DC compared to AG 490 or combination of both drugs. However the DC activation induced by all treatments was completely inhibited when these cells were pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT common receptor, CD91. The activation of DC by Bortezomib and AG 490 treated PEL cells, as seen in the present study, might have important implications for a combined chemo and immunotherapy in such patients

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Synthesis, Characterization, and Magnetic Studies of Coordination Polymers with Co(II) and Mn(II) Ions

An ether bridged tricarboxylic acid ligand, 5-(4-carboxybenzyloxy)­isophthalic acid (<i>p-</i>cbiaH₃) has been used to construct three coordination polymers with Co­(II) salts in presence of different nitrogen donor ligands such as 1,4-bis­(4-pyridinylmethyl)­piperazine (bpmp), dipyridine-4-yl-diazene (dpd), and 4,4′-bipyridine (bpy). The products formed under hydrothermal conditions are formulated as {[Co₃(<i>p</i>-cbia)₂(bpmp)₂(H₂O)₆]·10H₂O}_<i>n</i> (<b>1</b>), {[Co₂(<i>p</i>-cbiaH)₂(dpd)­(H₂O)₂]}_<i>n</i> (<b>2</b>) and {[Co₃(<i>p</i>-cbia)₂(bpy)­(H₂O)₈]·6H₂O}_<i>n</i> (<b>3</b>). Reacting with MnCl₂·4H₂O under solvothermal condition, it affords {[Mn₃(<i>p</i>-cbia)₂(DMF)₂]·DMF}_<i>n</i> (<b>4</b>). All the complexes have been characterized by single-crystal X-ray diffraction, IR spectroscopy, thermogravimetry, elemental analysis, and powder X-ray diffraction (PXRD) measurements. Topological analysis reveals that <b>1</b> is a (3,4)-connected jeb net, <b>2</b> is a (3,8)-connected tfz-d net, while <b>3</b> forms a 3-connected hcb type net. However, with the Mn­(II) salt, it forms a 3D coordination polymer with a novel (5,6,6)-connected, three nodal net with novel pkb-4 topology. Magnetic susceptibility measurements of complexes <b>1</b>, <b>2</b>, and <b>4</b> were carried out in the temperature range 2–300 K. Complex <b>1</b> exhibits weak ferromagnetic ordering at low temperature owing to the frustration of one of the Co­(II) ions in the unit cell. Complex <b>2</b> shows a peak at ∼6.1 K in ZFC susceptibility, which might result from weak ferromagnetic interactions between carboxylate-bridged Co­(II) ions. Complex <b>4</b> shows a signature of antiferromagnetic behavior followed by weak ferromagnetic interactions at low temperature

Syntheses, Crystal Structures, and Magnetic Properties of Metal–Organic Hybrid Materials of Co(II) Using Flexible and Rigid Nitrogen-Based Ditopic Ligands as Spacers

A carboxylate-based flexible ligand, 5-(4-carboxybenzyloxy)­isophthalic acid (<i>p</i>-cbiaH₃), readily reacts with Co­(II) salts in the presence of different pyridine-based coligands such as 4-bis­(4-pyridinylmethyl)­piperazine (bpmp) or 1,2-di­(4-pyridyl)­ethylene (dpe) under hydrothermal conditions to afford two different three-dimensional (3D) coordination polymers, {[Co₄(OH)₂(<i>p</i>-cbia)₂(bpmp)-(H_<b>2</b>O)₃]·2H₂O}_<i>n</i> (<b>1</b>) and {[Co₄(OH)₂(<i>p</i>-cbia)₂(dpe)­(H₂O)₄]·2H₂O}_<i>n</i> (<b>2</b>). Both compounds have been characterized by X-ray crystallography, IR spectroscopy, thermogravimetry, and elemental analysis. Single-crystal X-ray diffraction studies reveal that both compounds consist of a tetranuclear core [Co₄(μ₃-OH)₂]⁶⁺. Compound <b>1</b> is a unprecedented 3D non-interpenetrated (3,4,9)-connected <b>pkb3</b> net. On the other hand, compound <b>2</b> is a 2-fold interpenetrated (3,8)-connected <b>tfz-d</b> net. Variable temperature static and dynamic magnetic measurements show that both compounds exhibit ferromagnetic behavior associated with mixed hydroxyl/carboxylate-bridged tetranuclear Co­(II) clusters as subunits

Kras Gene Mutation and RASSF1A, FHIT and MGMT Gene Promoter Hypermethylation: Indicators of Tumor Staging and Metastasis in Adenocarcinomatous Sporadic Colorectal Cancer in Indian Population

<div><p>Objective</p><p>Colorectal cancer (CRC) development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease.</p> <p>Methods</p><p>One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls) of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed.</p> <p>Results</p><p>Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12) and MGMT methylation (p-value <0.049). Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044) and methylated RASSF1A (p-values 0.034, 0.044), FHIT (p-values 0.001, 0.047) and MGMT (p-values 0.018, 0.044) genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025). Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes.</p> <p>Conclusion</p><p>Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.</p> </div

Demographic profile and follow up of 62 patients with sporadic CRC.

*<p>Co morbidities include hypertension, diabetes, heart diseases and tuberculosis.</p

Tumor profile of 62 patients with sporadic CRC.

*<p>UM, unmethylated; M, methylated;</p>#<p>WD, well differentiated; MD, moderately differentiated; PD, poorly differentiated; U, undifferentiated.</p><p>p value <0.05 was taken as significant.</p