tbuckley/cabot-search huggingface dataset:
Transformed Follicular Lymphoma Mimicking Acute Lymphoblastic Leukemia
Authors: A. Ohmoto, Y. Kobayashi, S.-W. Kim, K. Miyamoto, S. Fukuhara, D. Maruyama, T. Watanabe, H. Taniguchi, A. Maeshima, K. Tobinai
Journal: Annals of Oncology (2013)
Human Breast Carcinoma: Fibrin Deposits ans Desmoplasia. Inflammatory Cell Type and Distribution. Microvasculature and Infarction&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Harold F. Dvorak, G. Richard Dickersin, Ann M. Dvorak, Eleanor J. Manseau, Kathryn Pyne
Journal: JNCI Journal of the National Cancer Institute (1981)

Study of 14 human infiltrating breast carcinomas revealed new features that shed light on the pathogenesis of tumor stroma formation and on host immunologic defense mechanisms. Fibrin deposits were observed in the stroma of all tumors, particularly at their growing edge. Fibrin may have contributed both to tumor angiogenesis and, with organization, to the formation of the fibrous stroma characteristic of these and other scirrhous carcinomas. We previously proposed similar mechanisms for several animal tumors. All breast carcinomas studied elicited some degree of lymphocytic response at the tumor periphery; lymphocytes penetrated the fibrous tumor stroma poorly, did not exit in significant numbers from central tumor vessels, and, even when greatly outnumbering tumor cells locally, appeared relatively ineffective at tumor cell killing. Microvascular endothelial cell damage was frequently observed and may have been responsible for zones of tumor infarction. Similar observations have been made in skin allografts and animal tumors where rejection was effected principally by microvascular damage and subsequent tissue infarction, not by lymphocyte contact with individual epithelial target cells.
Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer.
Authors: J M Nabholtz, K Gelmon, M Bontenbal, M Spielmann, G Catimel, P Conte, U Klaassen, M Namer, J Bonneterre, P Fumoleau, B Winograd
Journal: Journal of Clinical Oncology (1996)

The objective of this multicenter study was to compare the therapeutic index of two different doses of paclitaxel given as a 3-hour infusion in patients with metastatic breast cancer (MBC), who had failed to respond to previous chemotherapy. A total of 471 patients with MBC were randomized to receive intravenous paclitaxel at a dose of 175 or 135 mg/m2 every 3 weeks.Better treatment results were achieved with high-dose (HD) versus low-dose (LD) paclitaxel: overall response rate, 29% versus 22% (P = .108); complete response (CR) rate, 5% versus 2% (P = .088); median time to disease progression, 4.2 versus 3.0 months (P = .027); and median survival time, 11.7 versus 10.5 months (P = .321). Patients previously exposed or resistant to anthracyclines were as likely to respond as those without such prior exposure. Treatment was well tolerated, as documented by the number of administered treatment courses (median, six v five; range, one 17 v one to 18), the low frequency of dose reductions (14% v 7%, P = .024), and the small number of patients (n = 9 or 4% vn = 5 or 2%) who required treatment discontinuation for adverse reactions. The incidence and severity of neutropenia and peripheral neuropathy were dose-related. After quality-of-life-adjusted time-to-progression analysis, the HD arm (175 mg/m2) retained its advantage over the LD arm (135 mg/m2).The results of this trial substantiate the activity of paclitaxel in the treatment of MBC. The observed superior efficacy with a dose of 175 mg/m2 over 135 mg/m2 suggests a dose-effect relationship. The clinical activity in anthracycline-resistant patients is particularly noteworthy. Paclitaxel in breast cancer needs further evaluation in large trials that use combination chemotherapy and involve earlier disease stages.
Familial juvenile polyposis coli; increased risk of colorectal cancer.
Authors: H Jarvinen, K O Franssila
Journal: Gut (1984)

Six patients from one family and one solitary patient with juvenile polyposis coli are described. The histological changes in colonic polyps formed a spectrum from juvenile polyps, through focal to extensive adenomatous change, to adenocarcinomas. One patient aged 49 years had an adenocarcinoma of the colon and in another, aged 33, with rectal polyps and metastatic cancer this was suspected although the primary tumour was not located. Two additional patients, aged 19 and 41 years, had severe adenomatous dysplasia in a juvenile polyp. Four patients also had gastroduodenal polyps. The present findings clearly contradict the previous view that juvenile polyposis coli is not premalignant and only rarely needs surgical treatment. As other recent reports also describe frequent occurrence of neoplastic changes in juvenile polyps, colectomy, and ileorectostomy at the age of about 20 years is recommended as the treatment of choice for juvenile polyposis coli, as in patients with familial adenomatosis coli. Follow up should ideally include gastroduodenoscopy and inspection of the rectal remnant at regular intervals.
The Nuclear Receptor Coactivator Amplified in Breast Cancer-1 Is Required for <i>Neu</i> (ErbB2/HER2) Activation, Signaling, and Mammary Tumorigenesis in Mice
Authors: Mark P. Fereshteh, Maddalena T. Tilli, Sung Eun Kim, Jianming Xu, Bert W. O'Malley, Anton Wellstein, Priscilla A. Furth, Anna T. Riegel
Journal: Cancer Research (2008)

Abstract Overexpression of the oncogene amplified in breast cancer 1 (AIB1)/steroid receptor coactivator-3 (SRC-3) induces mammary tumorigenesis in mice. In breast cancer, high levels of AIB1/SRC-3 and the growth factor receptor HER2/neu predict resistance to endocrine therapy and poor outcome. However, a mechanistic relationship between AIB1/SRC-3 and HER2/neu in the development of breast cancer has not been shown. Here, we show that deletion of one allele of SRC-3 significantly delays Neu-induced mammary tumor development in mice. Homozygous deletion of SRC-3 in mice completely prevents Neu-induced tumor formation. By ages 3 to 4 months, Neu/SRC-3+/− mice exhibit a noticeable reduction in lateral side-bud formation, accompanied by reduced cellular levels of phosphorylated Neu compared with Neu/SRC-3wt mice. In Neu-induced tumors, high levels of SRC-3, phosphorylated Neu, cyclin D1, cyclin E, and proliferating cell nuclear antigen expression are observed, accompanied by activation of the AKT and c-Jun NH2 kinase (JNK) signaling pathways. In comparison, phosphorylated Neu, cyclin D1, and cyclin E are significantly decreased in Neu/SRC-3+/− tumors, proliferation is reduced, and AKT and JNK activation is barely detectable. Our data indicate that AIB1/SRC-3 is required for HER2/neu oncogenic activity and for the phosphorylation and activation of the HER2/neu receptor. We predict that reducing AIB1/SRC-3 levels or activity in the mammary epithelium could potentiate therapies aimed at inhibiting HER2/neu signaling in breast cancer. [Cancer Res 2008;68(10):3697–706]
MUC1 and Nuclear β-Catenin Are Coexpressed at the Invasion Front of Colorectal Carcinomas and Are Both Correlated with Tumor Prognosis
Authors: Stephan E. Baldus, Stefan P. Mönig, Sandra Huxel, Stephanie Landsberg, Franz-Georg Hanisch, Katja Engelmann, Paul M. Schneider, Jürgen Thiele, Arnulf H. Hölscher, Hans P. Dienes
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Overexpression of MUC1 and cytosolic interaction of the mucin with β-catenin are claimed to be involved in colorectal carcinogenesis. In vitro data published recently suggest that MUC1 overexpression results in an increase of steady state levels of nuclear β-catenin. We tried to elucidate the coexpression of both molecules in colorectal cancer to demonstrate possible correlations with clinical, pathological, and prognostic data. Experimental Design: An immunohistochemical double staining study was performed to characterize the expression and subcellular distribution of MUC1 and β-catenin in a series of 205 patients with colorectal carcinoma. The results were correlated with clinicopathological variables as well as overall survival. Results: MUC1 was strongly expressed in the tumor center and at the invasion front in ∼50% of the cases. Similar results were obtained with regard to nuclear accumulation of β-catenin at the invasive tumor parts. MUC1 protein expression in the tumor center correlated significantly with a low grade of differentiation, and nuclear β-catenin in the tumor periphery was more frequent in carcinomas of the left colon and rectum. Overexpression of MUC1 and β-catenin, as well as their nuclear coexpression at the invasion front correlated with a worse overall survival in an univariate analysis. However, only pathological tumor-node-metastasis staging and MUC1 at the invasion front revealed as independent prognostic factors. Conclusions: These results suggest that MUC1 and β-catenin are coexpressed at the invasion front of colorectal carcinomas and that this feature is associated with an accelerated course of disease and worse prognosis.
Phorbol myristate acetate: a mitogen selective for a T-lymphocyte subpopulation.
Authors: J L Touraine, J W Hadden, F Touraine, E M Hadden, R Estensen, R A Good
Journal: The Journal of Experimental Medicine (1977)

Phorbol myristate acetate (pma) is a potent mitogen for human peripheral blood lymphocytes (PBL) comparable to phytohemagglutinin (PHA) in potency. Inactivation of PHA-responsive lymphocytes by 5'-bromodeoxyuridine and light treatment left the PMA response intact and nice versa. Experiments separating lymphocytes by rosetting with sheep erythrocytes (SRBC) demonstrated that the PMA-responsive lymphocytes segregate with those that have a high affinity for SRBC to a greater than PHA- or concanavalin A (Con A)-responsive cells. These results indicate that a PMA-responsive population in human peripheral blood resides within the T-lymphocyte population and appears to have a high affinity for SRBC and to be distinct from that responding to PHA and Con A. PMA may be useful clinically to assay the size and function of the high affinity or "active" rosette population.
Wnt/β-catenin signaling promotes expansion of Isl-1–positive cardiac progenitor cells through regulation of FGF signaling
Authors: Ethan David Cohen, Zhishan Wang, John J. Lepore, Min Min Lu, Makoto M. Taketo, Douglas J. Epstein, Edward E. Morrisey
Journal: Journal of Clinical Investigation (2007)

The anterior heart field (AHF), which contributes to the outflow tract and right ventricle of the heart, is defined in part by expression of the LIM homeobox transcription factor Isl-1. The importance of Isl-1-positive cells in cardiac development and homeostasis is underscored by the finding that these cells are required for cardiac development and act as cardiac stem/progenitor cells within the postnatal heart. However, the molecular pathways regulating these cells' expansion and differentiation are poorly understood. We show that Isl-1-positive AHF progenitor cells in mice were responsive to Wnt/beta-catenin signaling, and these responsive cells contributed to the outflow tract and right ventricle of the heart. Loss of Wnt/beta-catenin signaling in the AHF caused defective outflow tract and right ventricular development with a decrease in Isl-1-positive progenitors and loss of FGF signaling. Conversely, Wnt gain of function in these cells led to expansion of Isl-1-positive progenitors with a concomitant increase in FGF signaling through activation of a specific set of FGF ligands including FGF3, FGF10, FGF16, and FGF20. These data reveal what we believe to be a novel Wnt-FGF signaling axis required for expansion of Isl-1-positive AHF progenitors and suggest future therapies to increase the number and function of these cells for cardiac regeneration.
Evolution of CRISPs Associated with Toxicoferan-Reptilian Venom and Mammalian Reproduction
Authors: K. Sunagar, W. E. Johnson, S. J. O'Brien, V. Vasconcelos, A. Antunes
Journal: Molecular Biology and Evolution (2012)

Cysteine-rich secretory proteins (CRISPs) are glycoproteins found exclusively in vertebrates and have broad diversified functions. They are hypothesized to play important roles in mammalian reproduction and in reptilian venom, where they disrupt homeostasis of the prey through several mechanisms, including among others, blockage of cyclic nucleotide-gated and voltage-gated ion channels and inhibition of smooth muscle contraction. We evaluated the molecular evolution of CRISPs in toxicoferan reptiles at both nucleotide and protein levels relative to their nonvenomous mammalian homologs. We show that the evolution of CRISP gene in these reptiles is significantly influenced by positive selection and in snakes (ω = 3.84) more than in lizards (ω = 2.33), whereas mammalian CRISPs were under strong negative selection (CRISP1 = 0.55, CRISP2 = 0.40, and CRISP3 = 0.68). The use of ancestral sequence reconstruction, mapping of mutations on the three-dimensional structure, and detailed evaluation of selection pressures suggests that the toxicoferan CRISPs underwent accelerated evolution aided by strong positive selection and directional mutagenesis, whereas their mammalian homologs are constrained by negative selection. Gene and protein-level selection analyses identified 41 positively selected sites in snakes and 14 sites in lizards. Most of these sites are located on the molecular surface (nearly 76% in snakes and 79% in lizards), whereas the backbone of the protein retains a highly conserved structural scaffold. Nearly 46% of the positively selected sites occur in the cysteine-rich domain of the protein. This directional mutagenesis, where the hotspots of mutations are found on the molecular surface and functional domains of the protein, acts as a diversifying mechanism for the exquisite biological targeting of CRISPs in toxicoferan reptiles. Finally, our analyses suggest that the evolution of toxicoferan-CRISP venoms might have been influenced by the specific predatory mechanism employed by the organism. CRISPs in Elapidae, which mostly employ neurotoxins, have experienced less positive selection pressure (ω = 2.86) compared with the "nonvenomous" colubrids (ω = 4.10) that rely on grip and constriction to capture the prey, and the Viperidae, a lineage that mostly employs haemotoxins (ω = 4.19). Relatively lower omega estimates in Anguimorph lizards (ω = 2.33) than snakes (ω = 3.84) suggests that lizards probably depend more on pace and powerful jaws for predation than venom.
Respiratory muscle strength in asthmatic children
Authors: Katerina Neumannova, Jakub Zatloukal, Zuzana Kovacikova, Jana Rydlova, Zuzana Jarosova
Journal: European Respiratory Journal (2014)

Introduction

Respiratory muscle weakness can lead to increased work of breathing, which can cause dyspnoea, however, it can also result in ineffective expectoration. Respiratory muscle strength (RMS) test is not commonly included in initial assessment of asthmatic children in the Czech Republic.

Aim

To assess RMS in children with mild intermittent asthma and to evaluate the effect of pulmonary rehabilitation programme (PRP) on RMS.

Methods

167 asthmatic children (11.8±3.0 years, FEV1 97.3±16.8 %) attended 4-week PRP (education, exercise programme, nutrition support) during spa treatment and underwent lung function tests and assessment of maximal inspiratory (PImax) and expiratory (PEmax) mouth pressures pre and post PRP.

Results

Not all asthmatics initially reached PImax and PEmax values above 80 % of predicted, PEmax was lower in 47 % of girls and in 35.7 % of boys, PImax in 41 % of girls and 33.3 % of boys. After PRP there was a significant improvement of RMS in almost all children, although better improvement was achieved in children with initially decreased RMS (table 1).

View this table:

Table 1. RMS in asthmatics (83 girls; 84 boys)





Conclusion

According to our results it is important to assess RMS in mild asthmatic children and in case that RMS is decreased the targeted therapy is necessary for its improvement.

The study was supported by a project No. CZ.1.07/2.3.00/30.0004.
Dangers Within
Authors: Diane L. Rosin, Mark D. Okusa
Journal: Journal of the American Society of Nephrology (2011)

The response to exogenous pathogens leads to activation of innate immunity through the release of pathogen-associated molecular patterns (PAMPs) and their binding to pattern recognition receptors. A classic example is septic shock where Toll receptor 4 recognizes PAMPs. Although well accepted, this concept does not explain the activation of innate immunity and inflammation occurs with transplantation, autoimmunity, or trauma. Increasingly recognized is that endogenous molecules released by dying cells (damage-associated molecular patterns; DAMPs) activate cellular receptors leading to downstream inflammation. Thus endogenous danger signals and exogenous PAMPs elicit similar responses through seemingly similar mechanisms. Also emerging is our understanding that normal repair processes benefit from dampening the immune response to these endogenous danger molecules. Here we focus on the role of DAMPs and their putative receptors in the pathogenesis of acute and chronic kidney diseases.
CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice
Authors: Christian Weber, Svenja Meiler, Yvonne Döring, Miriam Koch, Maik Drechsler, Remco T.A. Megens, Zuzanna Rowinska, Kiril Bidzhekov, Caroline Fecher, Eliana Ribechini, Marc A.M.J. van Zandvoort, Christoph J. Binder, Ivett Jelinek, Mihail Hristov, Louis Boon, Steffen Jung, Thomas Korn, Manfred B. Lutz, Irmgard Förster, Martin Zenke, Thomas Hieronymus, Tobias Junt, Alma Zernecke
Journal: Journal of Clinical Investigation (2011)

Immune mechanisms are known to control the pathogenesis of atherosclerosis. However, the exact role of DCs, which are essential for priming of immune responses, remains elusive. We have shown here that the DC-derived chemokine CCL17 is present in advanced human and mouse atherosclerosis and that CCL17+ DCs accumulate in atherosclerotic lesions. In atherosclerosis-prone mice, Ccl17 deficiency entailed a reduction of atherosclerosis, which was dependent on Tregs. Expression of CCL17 by DCs limited the expansion of Tregs by restricting their maintenance and precipitated atherosclerosis in a mechanism conferred by T cells. Conversely, a blocking antibody specific for CCL17 expanded Tregs and reduced atheroprogression. Our data identify DC-derived CCL17 as a central regulator of Treg homeostasis, implicate DCs and their effector functions in atherogenesis, and suggest that CCL17 might be a target for vascular therapy.
Tamoxifen, Raloxifene, and the Prevention of Breast Cancer*
Authors: V. Craig Jordan, Monica Morrow
Journal: Endocrine Reviews (1999)

I. Introduction II. Lacassagne’s Prevention Principle: A Target and an Estrogen Antagonist III. Tamoxifen as an Antitumor Agent A. ER status and the duration of tamoxifen B. Contralateral breast cancer C. Endometrial cancer D. Conclusions IV. Selective Estrogen Receptor Modulation A. Antiestrogen activity at the ER B. Coactivators for ER C. Alternate response elements on DNA D. An alternate ER-ERβ V. Biological Basis for Tamoxifen as a Breast Cancer Preventive A. Animal models B. Bones C. Lipids D. Uterus VI. Risk Factors for Breast Cancer A. Interactions among risk factors B. Identification of candidates for chemoprevention VII. Prevention of Breast Cancer with Tamoxifen A. Royal Marsden Pilot Study B. NSABP/NCI Study C. Italian study D. Conclusions VIII. Biological Basis for Raloxifene as a Breast Cancer Preventive A. Antitumor actions B. Bones C. Lipids D. Uterus IX. Study of Tamoxifen And Raloxifene (STAR) X. The Future of Prevention
Nucleus-Encoded Periplastid-Targeted EFL in Chlorarachniophytes
Authors: G. H. Gile, P. J. Keeling
Journal: Molecular Biology and Evolution (2008)

Chlorarachniophytes are cercozoan amoeboflagellates that acquired photosynthesis by enslaving a green alga, which has retained a highly reduced nucleus called a nucleomorph. The nucleomorph lacks many genes necessary for its own maintenance and expression, suggesting that some genes have been moved to the host nucleus and their products are now targeted back to the periplastid compartment (PPC), the reduced eukaryotic cytoplasm of the endosymbiont. Protein trafficking in chlorarachniophytes is therefore complex, including nucleus-encoded plastid-targeted proteins, nucleomorph-encoded plastid-targeted proteins, and nucleus-encoded periplastid-targeted proteins. A major gap in our understanding of this system is the PPC-targeted proteins because none have been described in any chlorarachniophytes. Here we describe the first such protein, the GTPase EFL. EFL was characterized from 7 chlorarachniophytes, and 2 distinct types were found. One is related to foraminiferan EFL and lacks an amino-terminal extension. The second, distantly related, type encodes an amino-terminal extension consisting of a signal peptide followed by sequence sharing many characteristics with transit peptides from nucleus-encoded plastid-targeted proteins and which we conclude is most likely PPC targeted. Western blotting with antibodies specific to putative host and PPC-targeted EFL from the chlorarachniophytes Bigelowiella natans and Gymnochlora stellata is consistent with posttranslational cleavage of the leaders from PPC-targeted proteins. Immunolocalization of both proteins in B. natans confirmed the cytosolic location of the leaderless EFL and a distinct localization pattern for the PPC-targeted protein but could not rule out a plastid location (albeit very unlikely). We sought other proteins with a similar leader and identified a eukaryotic translation initiation factor 1 encoding a bipartite extension with the same properties. Transit peptide sequences were characterized from all 3 classes of targeted protein by comparing all examples of each class from expressed sequence tag surveys of B. natans and G. stellata. No recognizable difference between plastid- and PPC-targeted proteins was observed, but nucleomorph-encoded transit peptides differ, likely reflecting high AT content of nucleomorph genomes. Taken together, the data suggest that the system that directs proteins to the PPC in chlorarachniophytes uses a bipartite targeting sequence, as does the PPC-targeting system that evolved independently in cryptomonads.
Is the trimodality of Hb leslie (α<sub>2</sub>β<sub>2</sub><sup>131</sup>Gln → 0) in heterozygotes the result of a variable number of active α‐chain genes? Evidence for posttranslational control of hemoglobin synthesis
Authors: A. Felice, E. C. Abraham, A. Miller, M. Stallings, T. H. J. Huisman
Journal: American Journal of Hematology (1978)

Abstract Whether the trimodality in the relative concentration of the hemoglobin variant Hb Leslie in heterozygotes (Huisman, Hemoglobin 1: 349–382, 1977) is due to a polymorphism of the α‐chain structural genes was investigated by conventional incubation of reticulocytes with 14 C‐leucine. In addition, an aliquot from each of the incubations was incubated under the same conditions but without isotope. Three Hb Leslie heterozygotes with presumably four, three (heterozygous α‐thalassemia‐2), and two (homozygous α‐thalassemia‐2) active α‐chain genes and with 33%, 22%, and 11% Hb Leslie respectively, and one patient with the Hb Leslie β 0 ‐thalassemia condition with more than 85% Hb Leslie were studied. The data indicate that β Leslie chains have a lower affinity for α chains than β A chains. A concomitant α‐chain deficiency results in a reduced incorporation of β Leslie chains into the tetrameric Hb Leslie molecules, while the quantity of Hb Leslie produced correlates with the degree of α‐chain deficiency. Excess of β Leslie chains is preferentially degraded.