Prominent Reaction Research Articles

Histiocytic Infiltrate in Angioimmunoblastic T-Cell Lymphoma with Cutaneous Nodules and Progressive Ulceration: A Rare Manifestation

Dear Editor: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive non-Hodgkin's nodal peripheral T-cell lymphoma that accounts for 18% of peripheral T-cell lymphoma, and cutaneous AITL has not been well characterized in terms of clinical and histopathologic features1. Because AITL is usually diagnosed based on lymph node biopsy, it is difficult for physicians to diagnose cutaneous AITL without lymphadenopathy. Eighty-four years old female visited our hospital with nodules on both calves. The patient claimed that she had first noticed tender nodules several months prior to the visit and that they have gradually increased in size (Fig. 1A). Examination results indicated skin-colored palpable hard nodules with tenderness, about 3.0×3.0 cm in size. The nodule histologically revealed prominent vascular proliferation surrounded by abundant epitheloid histiocytes and lymphocytes without prominent nuclear atypia in the dermis (Fig. 2A, B). There were many positive cells in CD3 and CD68 (Fig. 2C, D), foci of small aggregates of positive cells in CD31, and negative cells in S100 protein, CD1a and Epstein-Barr virus (EBV). T-cell receptor-γ gene rearrangement was found to be monoclonal. In suspicion of cutaneous T-cell lymphoma, she underwent further evaluation, such as laboratory test, whole-body computed tomography (CT), and positron emission tomography-CT in hemato-oncology. On a follow-up visit, the nodule on her left calf became a progressive ulcer with a granulation-like base (Fig. 1B). However, we could not find any evidence of infection. Inguinal lymphadenopathy was identified from imaging study, and lymph node biopsy was performed (Fig. 2F, G). Many cells in the lymph node showed positive reactions for CD3, CD4, CD5, CD21 and programmed death-1 (PD-1) (Fig. 2H~L), but negative reactions for CD8, CD20 and EBV. An additional stain for PD-1 of the skin was also positive (Fig. 2E). Based on these immunohistological findings, we were able to diagnose the skin lesion as AITL. After 6 months, she developed aggressive malignant lymphadenopathy in multiple regions of the body. Fig. 1 (A) Localized hard subcutaneous nodules about 3.0×3.0 cm in size with no epidermal changes were palpable on both calves. (B) After several weeks, the nodule on the left calf developed into a progressive ulcer covered with granulation-like tissues, ... Fig. 2 (A~E) Histopathological findings of skin biopsy. (A) Dense inflammatory cell infiltration into the deep dermis (H&E, ×40). (B) Numerous small to medium-sized vascular channels surrounded by densely mixed inflammatory cells, especially ... Skin involvement occurs in up to 50% of AITL patients and presents with nonspecific maculopapular eruption in most cases, but less commonly in patients with nodules1. Our patient first presented with cutaneous nodules, and histologically showed vascular proliferation with abundant histiocytic infiltration. Progressive ulceration made AITL diagnose more difficult until the lymph node biopsy result was obtained. However, PD-1 staining for the lymph node and the skin was useful in making the diagnosis2. Until now, predominant histiocytic infiltrate in cutaneous AITL such as our case has not been described. Only a few AITL cases have been reported with nodular lesion histologically showing presence of histiocytes. Although histiocytes' role in cutaneous lymphoma has been described in prominent granulomatous reaction, most cases were of mycosis fungoides3 and rare cases of AITL. CD68 has been known as negative prognostic marker for lymphoma-associated macrophage in follicular lymphoma4 and classic Hodgkin's lymphoma5. In our opinion, abundant histiocytic infiltration in cutaneous AITL may be associated with the cutaneous nodules and also with the progressive ulcer, and histiocytes might play a more aggressive role in the clinical features of AITL, which will be evaluated in the future.

Transition-Metal-Catalyzed Bioorthogonal Cycloaddition Reactions.

In recent years, bioorthogonal reactions have emerged as a powerful toolbox for specific labeling and visualization of biomolecules, even within the highly complex and fragile living systems. Among them, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is one of the most widely studied and used biocompatible reactions. The cytotoxicity of Cu(I) ions has been greatly reduced due to the use of Cu(I) ligands, which enabled the CuAAC reaction to proceed on the cell surface, as well as within an intracellular environment. Meanwhile, other transition metals such as ruthenium, rhodium and silver are now under development as alternative sources for catalyzing bioorthogonal cycloadditions. In this review, we summarize the development of CuAAC reaction as a prominent bioorthogonal reaction, discuss various ligands used in reducing Cu(I) toxicity while promoting the reaction rate, and illustrate some of its important biological applications. The development of additional transition metals in catalyzing cycloaddition reactions will also be briefly introduced.

Morphological aspects of the hepatic response to neoadjuvant therapy

IntroductionTherapy of metastatic colorectal carcinoma has greatly evolved in recent years. Surgery is still the best curative option and can improve survival in stage IV disease. Neoadjuvant chemotherapy (NAC) has emerged as a widely used therapeutic option before surgery. Pathologists have developed several systems to grade response, mainly adapting the grading systems used for the response in primary esophageal or rectal tumors. There are many reports confirming the prognostic utility of these grading systems. However, there have been fewer references to the potential significance of the pattern of histological response. The objective of the present study is to describe the histopathological lesions found in the tumor bed after NAC and their potential significance in terms of prognosis. Material and methodsWe reviewed the files of patients with colorectal carcinoma that developed hepatic metastasis during follow-up and received NAC before surgical resection of metastasis. We gathered demographic, analytical and morphological data of the cases, and also reviewed the hepatic resection samples to measure the pathological response to chemotherapy according to Blazer's criteria, and to define the predominant patterns of response (mucin pools, fibrosis or necrosis). We also determined the presence of satellitosis, measured the thickness of the tumor-normal interface (TNI) as proposed by Maru et al., and searched for vascular and bile duct invasion. All these pieces of information were collected in an Excel database and analyzed with SPSS 20.0 for Windows statistical package. The outcome measures were disease-free survival and overall survival in months since the first surgery to resect metastatic disease. ResultsFifty patients fulfilled the inclusion criteria for the present study. All of them had received a chemotherapeutic regimen mainly based on platinum, associated or not with targeted drugs (18% received anti-EGFR drugs and 24% anti-VEGFR drugs). Of the primaries, 66% were of sigmoid-rectal origin, and 32% of the cases showed a major histopathological response to therapy (including 3 cases with a complete response). In 76% of the tumors, the predominant histological pattern was necrosis, followed by fibrosis (57.4%). Mucin pools were the predominant feature in 23.4% of the tumors. We found satellitosis (microscopic tumor nodules separated by more than 1mm from the principal tumor) in 53.2% of the cases. A prominent inflammatory reaction was found in 19% of the cases, and it was mainly composed of lymphocytes and hystiocytes (70% of the cases). Vessel invasion was seen in 30% of the cases, and perineural invasion was only found in 4%. We found no case of bile duct invasion by the tumor. The thickness of the TNI measured less than 2.5mm in 60% of the present series. Statistical analysis of the series revealed that thickness of the tumor-liver interface was significantly associated with recurrence and overall survival. We found a significant association between response and thickness of the tumor-normal liver interface. In our series, the presence of satellitosis tended to predict a shorter DFS. The comparison of Kaplan–Meier curves with the log-rank test showed a significant association between overall survival and the presence of mucin pools and fibrosis in the tumor bed. The other histopathological factors did not predict differences in prognosis. These differences were independent of the use of targeted drugs. DiscussionThe pathological reports of hepatic metastasis from colorectal carcinoma resected after NAC usually indicate only the number, the size and the response of the tumor cells to therapy, apart from the distance to the resection margin of the specimen. Few reports have analyzed the possible prognostic significance of the different kinds of histopathological responses. The results of the present study indicate that those tumors with extensive pools of mucin show a significantly worse prognosis as compared to tumors with less mucin secretion. Fibrosis indicates a better prognosis, except when desmoplasia is present. Our study further supports the prognostic significance of the thickness of the tumor-hepatic interface. We conclude that pathology reports should specify the kind of histopathological response to therapy, besides grading it, because this might add significant prognostic information.

Ductular Reaction and the K7-19 Progenitor Cell Sequence in Vascular Liver Disease: A New Perspective to Pathogenetic Mechanisms of Injury and Repair

Background:Ductular reaction (DR), a process intricately connected with hepatocyte progenitor cells (HPCs) at the canal of Hering evokes considerable scientific interest. The present study was undertaken to (a) identify DR patterns in different subsets of hepatic vascular disease, (b) localize intermediate hepatobiliary progenitors activated in response to stresses to vascular flow while studying their K7/19 immunoexpression profiles, and (c) possibly provide new insights to pathogenesis. Methods: Forty-six cases of hepatic vasculopathy including Budd-Chiari syndrome [BCS] (11), acute hemorrhagic necrosis [AHN] (6), veno-occlusive disease [VOD] (7), non-cirrhotic portal fibrosis [NCPF] (10), extrahepatic portal vein obstruction [EHPVO] (10) and chronic venous congestion [CVC] (2) were randomly selected. Mean DR was scored as 1: 2–5, 2: 6–8, 3 > 8 after counting ductules per portal tract (D/ PT) separately on K7 and 19 immunostains. Extraportal ‘‘progenitors’’ were semiquantitatively graded as 0: None, 1: Occasional, 2: Significant number. This was done separately for hepatocytic and ductular cells on K7 & 19. Zonation effect, if any was noted. Results: DR, intermediate hepatocytic progenitors and extraportal ductules were seen in 69.5/45.6%, 84.7/30.4% and 65.2/50% cases respectively on K7/ 19 stain. DR was seenmost frequently in the subset of AHN (100%) and least in EHPVO (40%). All cases of BCS, AHN and CVC showed intermediate K7+ hepatocytic cells. Extraportal ductular cells (K7+/K19 ) were most common in AHN (100%) and showed a distinct centrilobular pattern. Conclusions: Derangements in vascular flow trigger prominent ductular reaction in all subsets of hepatic vasculopathy barring EHPVO. Severe parenchymal loss as seen in AHN activates both biliary and hepatocytic intermediate cells possibly as a response to extensive parenchymal cell loss. Vascular liver diseases show heterogeneity in K7/19 expression profiles of extraportal progenitors across all subsets, emphasizing that as a group vasculopathies may be trickier to reverse. Timely diagnosis hence is paramount tominimize damage. Corresponding author Tel: +91 9718599073: Puja Sakhuja. E-mail: pujasak@gmail.com

Role of pancreatic stellate cells and periostin in pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and one of the five most lethal malignancies characterized by prominent desmoplastic reaction. Accumulating evidences indicate that tumor desmoplasia plays a pivotal role in PDAC progression, and it has been largely ignored until recent times. It has now been unequivocally shown that pancreatic stellate cells (PSCs) are the principal effector cells responsible for stroma production. Periostin, also known as osteoblast-specific factor 2, is a secretory protein and originally identified as an osteoblast-specific factor that expressed in periosteum. Periostin is exclusively produced by activated PSCs, and periostin overexpression presents in various malignant tumors and closely relates with disease progression. In addition, periostin has been suggested to stimulate pancreatic cancer cells proliferation and enhance their resistance to serum starvation and hypoxia. Therefore, the interplay between cancer cells and stromal cells plays a vital role in PDAC development. However, the function of periostin in pancreatic cancer development is controversial. This review summarizes existing knowledge about the role of PSCs in cancer stroma production, the interaction between PSCs and pancreatic cancer cells, tumor angiogenesis, and hypoxic microenvironment, with particular focus on the expression and function as well as signaling pathways of periostin in PDAC cells and PSCs.

Reaction fronts formation during oxygen chemical diffusion in oxides

We present a theoretical study of the impact of oxygen diffusion in oxide crystals on the dynamic changes of metal dopants in the ionic state, and on the crystal conduction type. The analysis invokes ambipolar diffusion for all participating species: oxygen vacancies, metal dopant, holes and electrons. The species dynamics are demonstrated for an oxide of 8eV energy gap, electron and hole diffusivities being 105 times larger than the oxygen vacancy one, and the dopant energy level being 1.0eV above or 1.0eV below the mid-gap. We obtain linkage between the oxygen chemical diffusivity and the occurrence of a reaction front. The necessary condition is the existence of a sufficiently long interval, where a power dependence of the oxygen chemical diffusivity on the ambient oxygen pressure exists. In our demonstrated system, prominent reaction fronts occur at very low and at very high ambient oxygen pressures. The fronts relate to the reversible MMe×+e′→←MMe′ reaction at the low pressures, and to the reversible MMe′+h•→←MMe× reaction at high pressures, where M marks the dopant metal, and Me marks an oxide lattice constituent metal. In the mid-pressure interval, the oxygen chemical diffusivity is approximately constant, being several orders of magnitude smaller than the oxygen vacancy diffusivity.

Thermal degradation of phosphorus esters derived from isosorbide and 10-undecenoic acid

Phosphorus compounds derived from renewable biomaterials are of increasing interest as polymer additives. These compounds may have both a plasticizing and flame-retarding effect on a polymer matrix into which they are incorporated. The thermal degradation of a series of phosphorus esters derived from a diol generated by the esterification of isosorbide (from starch) with 10-undecenoic acid (from castor oil) followed by thiol-ene reaction with 2-hydroxyethanethiol has been examined using thermogravimetry and infrared spectroscopy. All the esters undergo degradation over the temperature range of 250–310 °C to generate a substantial residual char. Infrared analysis of samples undergoing degradation suggests that a prominent reaction is elimination of a phosphorus acid.

Decreased expression of human heat shock protein 70 in the endometria and pathological lesions of women with adenomyosis and uterine myoma after GnRH agonist therapy

ObjectiveA prominent stress reaction in the pelvis of women with endometriosis and the role of human heat shock protein 70 (HSP70) in inflammation and the growth of endometriosis has been recently demonstrated. We report here expression of HSP70 in tissues derived from GnRH agonist (GnRHa)-untreated and -treated women with adenomyosis and uterine myoma. Study designThis is a case-controlled biological study. Biopsy specimens were collected from pathological lesions and eutopic endometria/autologous myometria of 30 women with adenomyosis, 35 women with uterine myoma and 15 control women during laparoscopy, laparotomy and hysteroscopy. Fourteen women with adenomyosis and 20 women with uterine myoma were treated with GnRHa for a variable period of 3–6 months before surgery. The immunoexpressions of HSP70 and CD68-positive Mϕ in endometria, lesions/myometria were examined by immunohistochemistry. The immunoreactivity of HSP70 in tissues was analyzed by quantitative-histogram (Q-H) scores. ResultsComparing to control women, HSP70 immunoexpression was significantly higher in endometria/myometria and pathological lesions of women with adenomyosis and myoma. A significant positive correlation between Q-H scores of HSP70 and CD68-positive Mϕ numbers was found in the endometria derived from women with adenomyosis (r=0.388). Treatment with GnRHa significantly decreased Q-H scores of HSP70 in pathological lesions and endometria/myometria of women with adenomyosis and uterine myoma comparing to similar tissues derived from GnRHa-untreated women. ConclusionA variable amount of tissue stress reaction occurred in endometria and pathological lesions of women adenomyosis and uterine myoma that can be effectively suppressed after GnRHa treatment.

Reaction of Aluminum Cluster Cations with a Mixture of O2 and H2O Gases: Formation of Hydrated-Alumina Clusters

We present reactions of size-selected free aluminum cluster cations, AlN+ (N = 1–14), exposed to a mixture of water and oxygen gases. It is featured that chemical species assignable to Al2O6H7+ and Al2O7H9+ were commonly produced as prominent reaction products from all of the sizes, except N = 1. These product ions were found to be produced via the formation of Al2O3+ in the initial stage of reactions with O2 and H2O, which was followed by successive hydrogenation and hydration. This reaction pathway was identified by examining reactivity of each intermediate product step by step. Structures of the product ions were analyzed by collision-induced dissociation experiments and DFT calculations; for example, coexistence of isomers, Al2O5H5(H2O)+ and Al2O4H3(H2O)2+, with one and two intact H2O molecules, respectively, was suggested for Al2O6H7+. The chemical compositions of the ions produced in the present reactions are expressed nominally as Al2O3(H2O)nH+, which is similar, except for the proton, to that of h...

Oxidative IR spectroelectrochemistry of copper in methanol containing carbon monoxide.

IR spectroelectrochemistry was used to examine the electro-oxidation behavior of carbon monoxide in methanol at a polycrystalline copper electrode. Under such neutral conditions copper electrodes are coated with ill-defined copper oxides and hydroxides and at the oxidative potentials can be expected to generate soluble copper species. The electrochemistry displayed complex behavior suggesting that methanol oxidation was one prominent reaction. However, the spectroscopy revealed that very little methanol oxidation had occurred and that carbon monoxide was not adsorbed to the copper electrode. Instead, the electro-oxidation generated an intense IR band at 2107 cm(-1) that was attributed to a soluble [Cu(I)CO](+) species.

Assessment of electrochemical properties of a biogalvanic system for tissue characterisation

Biogalvanic characterisation is a promising method for obtaining health-specific tissue information. However, there is a dearth of understanding in the literature regarding the underlying galvanic cell, electrode reactions and their controlling factors which limits the application of the technique.This work presents a parametric electrochemical investigation into a zinc–copper galvanic system using salt (NaCl) solution analogues at physiologically-relevant concentrations (1.71, 17.1 & 154mM). The potential difference at open cell, closed cell maximum current and the internal resistance (based on published characterisation methods) were measured. Additionally, independent and relative polarisation scans of the electrodes were performed to improve understanding of the system.Our findings suggest that the prominent reaction at the cathode is that of oxygen-reduction, not hydrogen-evolution. Results indicate that cell potentials are influenced by the concentration of dissolved oxygen at low currents and maximum closed cell currents are limited by the rate of oxygen diffusion to the cathode. Characterised internal resistance values for the salt solutions did not correspond to theoretical values at the extremes of concentration (1.71 and 154mM) due to electrode resistance and current limitation. Existing biogalvanic models do not consider these phenomena and should be improved to advance the technique and its practical application.

Abstract 3824: c-MET as a prognostic biomarker and therapeutic target in patients with poor prognostic pancreatic adenocarcinoma following surgical resection

Abstract Context: Pancreatic ductal adenocarcinoma (PDAC) displays a prominent desmoplastic stromal reaction, leading to tumor hypoxia and driving a selective pressure towards cancer cells with aggressive phenotype. Activation of the HGF/c-MET pathway is involved in tumor-stroma interactions and promotes PDAC cells proliferation, invasion, EMT, and stem cellness. As a background for identifying tumors that could benefit from MET inhibitors, we set a study looking at c-MET expression in PDAC and its association with clinical/pathological features, hypoxia, and survival. Patients and methods: Patients who underwent curative surgical resection for PDAC and received no adjuvant chemotherapy (“pure” prognostic value) were selected for this study. c-MET expression was assessed using immunochemistry and graded on a scale (combining the intensity of staining and the % of stained cells) from 0 to 4, along with the microenvironment characteristics as defined by HIF-1α and CA9 immunostaining (hypoxia), CD31 expression (microvascular density [MVD]), and stroma abundance. Clinical, pathological, and molecular biomarkers have been correlated with disease-free (DFS) and overall (OS) survivals. Results: thirty-seven patients have been analyzed in this study. Twenty-seven percent of tumors (10/37) were c-MET high (score ≥ 3). High c-MET expression was associated with moderate/poor differentiation (p = 0.017), presence of isolated tumor cells in the stroma (p = 0.023), and low stroma abundance (r = -0.445, p = 0.0074), but not with hypoxia-related markers (HIF-1α, CA9, or MVD). High c-MET expression was associated with shorter DFS (median: 7.7 vs 33.0 months, HR = 2.207, p=0.025) and OS (median: 12.1 vs 38.9 months, HR = 2.207, p=0.0099) than low c-MET expression in PDAC. High c-MET expression combined with tumor size > 20 mm and lymph node ratio (defined as the ratio of lymph nodes with tumor metastasis to the total lymph nodes dissected) > 0.20 predicted risk of early local or distant recurrence (RFS < 12 months) with an AUC = 0.833. Results of computer-assisted evaluation of c-MET expression, and correlation between c-MET expression assessed on entire tumor section and tissue microarray will be presented. Conclusion: c-MET appears to be a strong prognostic marker in resected PDAC that may help to identify patients at high risk of early recurrence. c-MET was not correlated with hypoxia in this study, but was associated with aggressive tumor features (poor differentiation, isolated tumor cells in the stroma, low stroma abundance). PDAC overexpressing c-MET may represent a subgroup candidate for intensified adjuvant treatment or clinical trials with MET inhibitors. Citation Format: Cindy NEUZILLET, Jérôme CROS, Annemilaï TIJERAS-RABALLAND, Julien MOROCH, Louis DE MESTIER, Pierre BEDOSSA, Valérie PARADIS, Alain SAUVANET, Jean-Baptiste BACHET, Armand DE GRAMONT, Esteban CVITKOVIC, Eric RAYMOND, Pascal HAMMEL, Anne COUVELARD. c-MET as a prognostic biomarker and therapeutic target in patients with poor prognostic pancreatic adenocarcinoma following surgical resection. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3824. doi:10.1158/1538-7445.AM2014-3824

Porous polymers based on aryleneethynylene building blocks.

Porous conjugated polymers are synthesized by metal-catalyzed coupling reactions. The progress for porous polymers when planar or tetrahedral building blocks are connected by alkyne units into novel materials is highlighted. The most prominent reaction for the buildup of the microporous alkyne-bridged polymers is the Sonogashira reaction, connecting alkynes to aromatic iodides or bromides. The availability of the building blocks and the potency of the Sonogashira reaction allow preparing a large variety of intrinsically porous polymeric materials, in which rigid struts connect multipronged centers. The microporous polymers are used as catalysts and as storage materials for gases and sensors. Postfunctionalization schemes, understanding of structure-property relationships, and the quest for high porosity are pertinent.

Effect of various additives on morphological and structural characteristics of pulse electrodeposited tin coatings from stannous sulfate electrolyte

Abstract The pulse electrodeposited tin coatings are synthesized from an acidic electrolyte (stannous sulfate, SnSO 4 30 g/L and sulfuric acid, H 2 SO 4 —200 g/L) containing various additives (polyethylene glycol (PEG), thiourea and Triton X-100). The effect of the additives on surface morphology, preferred orientation of grains, grain size, and surface roughness has been studied. The final coatings are characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and surface profilometry. In the absence of additives, tin deposition is associated with prominent hydrogen evolution reaction giving rise to rough deposits. Both PEG and thiourea act as grain refiner while Triton X-100 acts as a brightener in the electrolyte. The cathodic polarization on the reduction of the tin (II) ions is more pronounced when a combination of additives is used and further, fine-grained, smooth and shiny electrodeposits of tin are obtained due to a synergistic effect of the adsorbed species.

Surrounding pancreatic adenocarcinoma by killer mesenchymal stromal/stem cells.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic malignancy still associated with an unacceptably poor prognosis. In addition to neoplastic tissue, PDAC is characterized by a prominent desmoplastic reaction infiltrating and surrounding cancer cells (Chu et al., 2007). This fibrotic microenvironment is generated predominantly by stromal cells known as tumor-associated fibroblasts, the origin of which has been also attributed to mesenchymal stromal/stem cells (MSCs) deriving from either bone marrow (BM) or adipose tissue (AD) (Grisendi et al., 2011). Because MSCs can be induced to produce anticancer molecules, such as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) (Grisendi et al., 2010), we here show the impact of gene-modified human MSCs producing TRAIL against PDAC. The BxPC3 cell line (Fig. 1, left) was selected on the basis of its high expression of functional TRAIL receptors associated with recombinant human TRAIL sensitivity confirmed in a dose–response assay (data not shown). FIG. 1. Pancreatic adenocarcinoma cell line BxPC3 interplays with adipose-derived mesenchymal stem cells expressing green fluorescent protein (GFP AD-MSCs) only or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/GFP AD-MSCs). Scale bar, 50 μm. ... Microscopic examination of cocultures (Fig. 1, middle) of BxPC3 cells with adipose-derived MSCs expressing green fluorescent protein (GFP AD-MSCs), as control, revealed a peculiar interaction between MSCs and tumor cells, with BxPC3 cells arranged as islets surrounded by green AD-MSC bundles, in parallel to what is described for the PDAC-associated desmoplastic reaction in vivo (Chu et al., 2007). Having proved the interaction between GFP AD-MSCs and BxPC3 cells, coculture experiments were then performed for both 24 and 48 hr, testing various target-to-effector (T:E) ratios (1:1, 1:2, and 1:5), using TRAIL/GFP AD-MSCs. Tumor cell death was detected in all tested conditions. The interplay between TRAIL/GFP AD-MSCs and BxPC3 cells was followed by a breakdown of tumor islets together with the disruption of adherent BxPC3 cells, resulting in clusters of dead floating elements in culture medium above an established layer of TRAIL/GFP AD-MSCs (Fig. 1, right; T:E ratio, 1:2 at 48 hr; scale bar, 50 μm). These morphological findings were quantified by flow cytometric detection (data not shown) of apoptotic propidium iodide-positive cells, reaching 69±3% (average±SD) for TRAIL/GFP AD-MSCs versus 14±1% for GFP AD-MSCs (p=0.001 by two-tailed t test). Similar features were observed in cocultures of TRAIL/GFP AD-MSCs and an additional PDAC cell line (MIA PaCa-2 cells; data not shown). Depicting the strong interaction with genetically modified AD-MSCs and PDAC lines, we here suggest MSCs as suitable vectors for anticancer agent delivery, opening novel therapeutic opportunities for this still incurable cancer.

Formation of Allenes by 1,4-Addition of Intermolecular Phosphane/Borane Frustrated Lewis Pairs to a Conjugated Enyne

The t-Bu3P/B(C6F5)3 frustrated Lewis pair (6a) undergoes competing acetylene deprotonation (to give the phosphonium–alkenylborate salt 8) and 1,4-P/B FLP addition to the conjugated enyne 2-methylbutenyne to yield the zwitterionic allene derivative 9a. The less basic (o-tolyl)3P/B(C6F5)3 system (6b) avoids the acetylene deprotonation pathway. The zwitterionic allene derivative 9b formed by 1,4-P/B FLP addition to the enyne is again a prominent reaction product; here competing 1,2-addition is observed to give the olefinic product 10. The allene derivatives 9a and 9b and their competing products 8 and 10 were characterized by X-ray diffraction.

Ab Initio Investigation of the Thermal Decomposition of n-Butylcyclohexane

Environmental and energy security concerns have motivated an increased focus on developing clean, efficient combustors, which increasingly relies on insight into the combustion chemistry of fuels. In particular, naphthenes (cycloalkanes and alkylcycloalkanes) are important chemical components of distillate fuels, such as diesel and jet fuels. As such, there is a growing interest in describing napthene reactivity with kinetic mechanisms. Use of these mechanisms in predictive combustion models aids in the development of combustors. This study focuses on the pyrolysis of n-butylcyclohexane (n-BCH), an important representative of naphthenes in jet fuels. Seven different unimolecular decomposition pathways of C-C bond fission were explored utilizing ab initio/DFT methods. Accurate reaction energies were computed using the high-level quantum composite G3B3 method. Variational transition state theory, Rice-Ramsperger-Kassel-Marcus/master equation simulations provided temperature- and pressure-dependent rate constants. Implementation of these pathways into an existing chemical kinetic mechanism improved the prediction of experimental OH radical and H2O speciation in shock tube oxidation. Simulations of this combustion showed a change in the expected decomposition chemistry of n-BCH, predicting increased production of cyclic alkyl radicals instead of straight-chain alkenes. The most prominent reaction pathway for the decomposition of n-BCH is n-BCH = C3H7 + C7H13. The results of this study provide insight into the combustion of n-BCH and will aid in the future development of naphthene kinetic mechanisms.

Granulomatous syringotropic mycosis fungoides with two lesions having reactive B-cell proliferation

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. The diagnosis of MF may occasionally be challenging, particularly for variants of MF such as folliculotropic MF, syringotropic MF and granulomatous MF. Herein, we describe a case of MF in which syringotropism and a prominent granulomatous reaction were noted around the affected eccrine gland. This case represents a rare example of MF with multiple unusual histopathological features, including syringotropism, a granulomatous reaction and a reactive B-cell proliferation.

Mechanical Properties of Membranes of Poly(L-co-DL-lactic acid) with Poly(caprolactone triol) and StudyIn Vivo

There is increasing interest in aliphatic polyesters from lactones and lactides because of their biodegradability and biocompatibility. Among these compounds, poly(lactide), and poly(glycolide), poly(ε-caprolactone) and their copolymers are especially interesting because of their potential applications as biomedical materials. The aim of this study was to examine the properties of membranes of poly(L-co-D,L lactic acid) (PLDLA) with poly(caprolactone triol) (PCL-T) obtained by solvent evaporation. The blends were characterized by differential scanning calorimetry, dynamic mechanical analysis, Fourier transform infrared spectroscopy, and tensile strength tests. Based on the results ofin vitrostudies, PLDLA/PCL-T blends of 100/0 and 90/10 were implanted in subcutaneous tissue of Wistar rats for 1, 3, 7, 15, and 60 days to evaluate their biocompatibility. Histological analysis indicated that, although PCL-T-containing membranes caused a more prominent inflammatory reaction in the initial time intervals, by 60 days after implantation, the material was surrounded by dense, organized collagen with almost no inflammatory infiltrate.

Idiopathic scrotal calcinosis: A case series

Idiopathic calcinosis of the scrotum is a rare benign local condition, characterized by multiple, painless, hard scrotal nodules, in the absence of any systemic metabolic disorder. We report nine cases of this rare entity diagnosed over a five-year period (2009-2013). The patients' age ranged from 26 to 65 years (Mean 42 years). The majority presented with scrotal swellings (8/9) and were clinically diagnosed as sebaceous cysts (7/9). Two cases also gave history of white chalky discharge from the swelling. Associated features of right inguinal hernia and left hematocele were seen in two cases. Five cases presented with a solitary nodule, with the size ranging from 0.5 to 3 cm (Mean 1.89 cm). The histopathological examination revealed dermal calcified masses with prominent foreign body reaction. All cases underwent surgical excision and showed no recurrence in follow up. This case series attempts to create an awareness of this rare pathology, which has an obscure pathogenesis and is often misdiagnosed.