bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Rembrandt: Helping Personalized Medicine Become a Reality through Integrative Translational Research
Authors: Madhavan Subha , Zenklusen Jean-Claude , Kotliarov Yuri , Sahni Himanso , Fine Howard A. , Buetow Kenneth
Published: April 2023

Abstract
Finding better therapies for the treatment of brain tumors is hampered by the lack of consistently obtained molecular data in a large sample set and the ability to integrate biomedical data from disparate sources enabling translation of therapies from bench to bedside. Hence, a critical factor in the advancement of biomedical research and clinical translation is the ease with which data can be integrated, redistributed, and analyzed both within and across functional domains. Novel biomedical informatics infrastructure and tools are essential for developing individualized patient treatment based on the specific genomic signatures in each patient's tumor. Here, we present Repository of Molecular Brain Neoplasia Data (Rembrandt), a cancer clinical genomics database and a Web-based data mining and analysis platform aimed at facilitating discovery by connecting the dots between clinical information and genomic characterization data. To date, Rembrandt contains data generated through the Glioma Molecular Diagnostic Initiative from 874 glioma specimens comprising ∼566 gene expression arrays, 834 copy number arrays, and 13,472 clinical phenotype data points. Data can be queried and visualized for a selected gene across all data platforms or for multiple genes in a selected platform. Additionally, gene sets can be limited to clinically important annotations including secreted, kinase, membrane, and known gene-anomaly pairs to facilitate the discovery of novel biomarkers and therapeutic targets. We believe that Rembrandt represents a prototype of how high-throughput genomic and clinical data can be integrated in a way that will allow expeditious and efficient translation of laboratory discoveries to the clinic. (Mol Cancer Res 2009;7(2):157–67)
Data from Osteoclast-Derived Matrix Metalloproteinase-9 Directly Affects Angiogenesis in the Prostate Tumor–Bone Microenvironment
Authors: Bruni-Cardoso Alexandre , Johnson Lindsay C. , Vessella Robert L. , Peterson Todd E. , Lynch Conor C.
Published: April 2023

Abstract
In human prostate to bone metastases and in a novel rodent model that recapitulates prostate tumor–induced osteolytic and osteogenic responses, we found that osteoclasts are a major source of the proteinase, matrix metalloproteinase (MMP)-9. Because MMPs are important mediators of tumor-host communication, we tested the effect of host-derived MMP-9 on prostate tumor progression in the bone. To this end, immunocompromised mice that were wild-type or null for MMP-9 received transplants of osteolytic/osteogenic-inducing prostate adenocarcinoma tumor tissue to the calvaria. Surprisingly, we found that that host MMP-9 significantly contributed to prostate tumor growth without affecting prostate tumor–induced osteolytic or osteogenic change as determined by microcomputed tomography, microsingle-photon emission computed tomography, and histomorphometry. Subsequent studies aimed at delineating the mechanism of MMP-9 action on tumor growth focused on angiogenesis because MMP-9 and osteoclasts have been implicated in this process. We observed (a) significantly fewer and smaller blood vessels in the MMP-9 null group by CD-31 immunohistochemistry; (b) MMP-9 null osteoclasts had significantly lower levels of bioavailable vascular endothelial growth factor-A164; and (c) using an aorta sprouting assay, conditioned media derived from wild-type osteoclasts was significantly more angiogenic than conditioned media derived from MMP-9 null osteoclasts. In conclusion, these studies show that osteoclast-derived MMP-9 affects prostate tumor growth in the bone microenvironment by contributing to angiogenesis without altering prostate tumor–induced osteolytic or osteogenic changes. Mol Cancer Res; 8(4); 459–70. ©2010 AACR.
Data from Proteolytic Activation of Pro-Macrophage-Stimulating Protein by Hepsin
Authors: Ganesan Rajkumar , Kolumam Ganesh A. , Lin S. Jack , Xie Ming-Hong , Santell Lydia , Wu Thomas D. , Lazarus Robert A. , Chaudhuri Amitabha , Kirchhofer Daniel
Published: April 2023

Abstract
Macrophage-stimulating protein (MSP) is a plasminogen-related growth factor and ligand for the receptor tyrosine kinase RON. The MSP/RON system promotes wound healing and invasive tumor growth and suppresses proinflammatory immune response. MSP binding to RON requires proteolytic conversion of the inactive single-chain form (pro-MSP) into the disulfide-linked α/β heterodimer. The pro-MSP cleavage sequence (Ser-Lys-Leu-Arg483↓Val484) closely matches the substrate recognition sequences of hepsin, a type II transmembrane serine protease, that is overexpressed in several cancers. Here, we show that recombinant hepsin cleaves pro-MSP at the consensus site Arg483-Val484 with superior efficiency compared with the known activators MT-SP1 and hepatocyte growth factor activator (HGFA). At least 50% of pro-MSP was processed within 1 hour at a hepsin concentration of 2.4 nmol/L and at a molar enzyme to substrate ratio of 1:500. An uncleavable single-chain variant of MSP weakly bound to a RON–Fc fusion protein, whereas hepsin-cleaved MSP bound with a KD of 10.3 nmol/L, suggesting that the high-affinity binding site in MSP β-chain was properly formed. LNCaP prostate cancer cells overexpressing hepsin on the cell surface efficiently activated pro-MSP, which was blocked by a specific anti-hepsin antibody. Incubation of pro-MSP with hepsin led to robust RON-mediated phosphorylation of mitogen-activated protein kinase, ribosomal S6 protein, and Akt in human A2780 ovarian carcinoma cells stably expressing RON protein. In macrophages, pro-MSP with hepsin induced chemotaxis and attenuated lipopolysaccharide-dependent production of nitric oxide. These findings suggest that the MSP/RON signaling pathway may be regulated by hepsin in tissue homeostasis and in disease pathologies, such as in cancer and immune disorders. Mol Cancer Res; 9(9); 1175–86. ©2011 AACR.
Data from Mutational and Functional Analysis Reveals ADAMTS18 Metalloproteinase as a Novel Driver in Melanoma
Authors: Wei Xiaomu , Prickett Todd D. , Viloria Cristina G. , Molinolo Alfredo , Lin Jimmy C. , Cardenas-Navia Isabel , Cruz Pedro , Rosenberg Steven A. , Davies Michael A. , Gershenwald Jeffrey E. , López-Otín Carlos , Samuels Yardena
Published: April 2023

Abstract
The disintegrin-metalloproteinases with thrombospondin domains (ADAMTS) genes have been suggested to function as tumor suppressors as several have been found to be epigenetically silenced in various cancers. We performed a mutational analysis of the ADAMTS gene family in human melanoma and identified a large fraction of melanomas to harbor somatic mutations. To evaluate the functional consequences of the most commonly mutated gene, ADAMTS18, six of its mutations were biologically examined. ADAMTS18 mutations had little effect on melanoma cell growth under standard conditions, but reduced cell dependence on growth factors. ADAMTS18 mutations also reduced adhesion to laminin and increased migration in vitro and metastasis in vivo. Melanoma cells expressing mutant ADAMTS18 had reduced cell migration after short hairpin RNA–mediated knockdown of ADAMTS18, suggesting that ADAMTS18 mutations promote growth, migration, and metastasis in melanoma. Mol Cancer Res; 8(11); 1513–25. ©2010 AACR.
Data from IFN-Induced Protein with Tetratricopeptide Repeats 2 Inhibits Migration Activity and Increases Survival of Oral Squamous Cell Carcinoma
Authors: Lai Kuo-Chu , Chang Kuo-Wei , Liu Chung-Ji , Kao Shou-Yen , Lee Te-Chang
Published: April 2023

Abstract
The function of the IFN-stimulated gene family protein, IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), is poorly understood. Here, we report that IFIT2 colocalizes with cytokeratin 18 in oral squamous cell carcinoma (OSCC) cells. Treatment of OSCC cells with IFN-β significantly increased the expression of IFIT2 and remarkably inhibited cell migration. To further explore the effect of IFIT2 on cell migration, IFIT2 expression was either silenced with a small interfering RNA or increased by ectopic expression. IFIT2 knockdown in OSCC cells led to a significantly higher level of migration in vitro (P < 0.05) compared with control cells; by contrast, IFIT2 overexpression led to a significantly lower level of migration in vitro (P < 0.05). Immunohistochemically, 71.4% of OSCC tissues had elevated IFIT2 protein levels compared with noncancerous matched tissues. Elevated IFIT2 protein expression was positively associated with tumor differentiation status and inversely associated with nodal stage in OSCC specimens (P < 0.05). Higher IFIT2 protein levels in tumor tissues were also associated with better patient survival (P < 0.01). Our present study shows an inverse correlation between IFIT2 expression and cell migration, suggesting that IFIT2 plays an important role in inhibiting this process and that its expression may be associated with better prognosis in patients with OSCC. (Mol Cancer Res 2008;6(9):1431–9)
Data from FOXO Transcription Factors Enforce Cell Cycle Checkpoints and Promote Survival of Hematopoietic Cells after DNA Damage
Authors: Lei Hong , Quelle Frederick W.
Published: April 2023

Abstract
The PI3K/AKT signaling pathway contributes to cell cycle progression of cytokine-dependent hematopoietic cells under normal conditions, and it is absolutely required to override DNA damage–induced cell cycle arrest checkpoints in these cells. Phosphatidylinositol-3-kinase (PI3K)/AKT activity also correlates with Cdk2 activity in hematopoietic cells, suggesting that Cdk2 activation may be a relevant end point for this signaling pathway. However, mediators downstream of AKT in this pathway have not been defined. The forkhead transcription factor O (FOXO) family are negatively regulated by AKT-dependent phosphorylation and are known regulators of genes affecting cell cycle progression. We show that enhanced FOXO activity replicates the effect of PI3K inhibitors in enforcing G1 and G2 phase arrest after DNA damage. Conversely, knockdown of endogenous FOXO proteins increased Cdk2 activity and overrode DNA damage checkpoints in cells lacking PI3K activity. Moreover, loss of FOXO activity caused an increase in sensitivity to cisplatin-induced cell death, which was associated with failure to arrest cell cycle progression in the face of DNA damage caused by this chemotherapeutic agent. These cell cycle arrests were dependent on p27 expression when mediated by FOXO3a alone, but also involve p27-independent mechanisms when promoted by endogenous FOXO proteins. Together, these observations show that FOXO proteins enforce DNA damage–induced cell cycle arrest in hematopoietic cells. Inhibition of FOXO activity by cytokine-induced PI3K/AKT signaling is sufficient to override these DNA damage–induced cell cycle checkpoints, but may negatively impact hematopoietic cell viability. (Mol Cancer Res 2009;7(8):1294–303)
Data from Constitutive Suppressor of Cytokine Signaling 3 Expression Confers a Growth Advantage to a Human Melanoma Cell Line
Authors: Komyod Waraporn , Böhm Markus , Metze Dieter , Heinrich Peter C. , Behrmann Iris
Published: April 2023

Abstract
The growth of melanocytes and many early stage melanoma cells can be inhibited by cytokines, whereas late stage melanoma cells have often been reported to be “multi-cytokine–resistant.” Here, we analyzed the melanoma cell line 1286, resistant towards the growth-inhibitory effects of interleukin 6 (IL-6), and oncostatin M (OSM), to better understand the mechanisms underlying cytokine resistance. Although the relevant receptors gp130 and OSMR are expressed at the cell surface of these cells, cytokine stimulation hardly led to the activation of Janus kinase 1 and signal transducer and activator of transcription (STAT)3 and STAT1. We found a high-level constitutive expression of suppressors of cytokine signaling 3 (SOCS3) that did not further increase after cytokine treatment. Importantly, upon suppression of SOCS3 by short interfering RNA, cells became susceptible towards OSM and IL-6: they showed an enhanced STAT3 phosphorylation and a dramatically increased STAT1 phosphorylation. Moreover, suppression of SOCS3 rendered 1286 cells sensitive to the antiproliferative action of IL-6 and OSM, but not of IFN-α. Interestingly, SOCS3–short interfering RNA treatment also increased the growth-inhibitory effect in cytokine-sensitive WM239 cells expressing SOCS3 in an inducible way. Thus, SOCS3 expression confers a growth advantage to these cell lines. Constitutive SOCS3 mRNA expression, although at lower levels than in 1286 cells, was found in nine additional human melanoma cell lines and in normal human melanocytes, although at the protein level, SOCS3 expression was marginal at best. However, in situ analysis of human melanoma specimens revealed SOCS3 immunoreactivity in 3 out of 10 samples, suggesting that in vivo SOCS3 may possibly play a role in IL-6 resistance in at least a fraction of tumors. (Mol Cancer Res 2007;5(2):271–81)
Data from Breast Cancer Molecular Signatures as Determined by SAGE: Correlation with Lymph Node Status
Authors: Abba Martín C. , Sun Hongxia , Hawkins Kathleen A. , Drake Jeffrey A. , Hu Yuhui , Nunez Maria I. , Gaddis Sally , Shi Tao , Horvath Steve , Sahin Aysegul , Aldaz C. Marcelo
Published: April 2023

Abstract
Global gene expression measured by DNA microarray platforms have been extensively used to classify breast carcinomas correlating with clinical characteristics, including outcome. We generated a breast cancer Serial Analysis of Gene Expression (SAGE) high-resolution database of ∼2.7 million tags to perform unsupervised statistical analyses to obtain the molecular classification of breast-invasive ductal carcinomas in correlation with clinicopathologic features. Unsupervised statistical analysis by means of a random forest approach identified two main clusters of breast carcinomas, which differed in their lymph node status (P = 0.01); this suggested that lymph node status leads to globally distinct expression profiles. A total of 245 (55 up-modulated and 190 down-modulated) transcripts were differentially expressed between lymph node (+) and lymph node (−) primary breast tumors (fold change, ≥2; P < 0.05). Various lymph node (+) up-modulated transcripts were validated in independent sets of human breast tumors by means of real-time reverse transcription-PCR (RT-PCR). We validated significant overexpression of transcripts for HOXC10 (P = 0.001), TPD52L1 (P = 0.007), ZFP36L1 (P = 0.011), PLINP1 (P = 0.013), DCTN3 (P = 0.025), DEK (P = 0.031), and CSNK1D (P = 0.04) in lymph node (+) breast carcinomas. Moreover, the DCTN3 (P = 0.022) and RHBDD2 (P = 0.002) transcripts were confirmed to be overexpressed in tumors that recurred within 6 years of follow-up by real-time RT-PCR. In addition, meta-analysis was used to compare SAGE data associated with lymph node (+) status with publicly available breast cancer DNA microarray data sets. We have generated evidence indicating that the pattern of gene expression in primary breast cancers at the time of surgical removal could discriminate those tumors with lymph node metastatic involvement using SAGE to identify specific transcripts that behave as predictors of recurrence as well. (Mol Cancer Res 2007;5(9):881–90)
Data from Phosphatidylethanol Accumulation Promotes Intestinal Hyperplasia by Inducing ZONAB-Mediated Cell Density Increase in Response to Chronic Ethanol Exposure
Authors: Pannequin Julie , Delaunay Nathalie , Darido Charbel , Maurice Tangui , Crespy Philippe , Frohman Michael A. , Balda Maria S. , Matter Karl , Joubert Dominique , Bourgaux Jean-François , Bali Jean-Pierre , Hollande Frédéric
Published: April 2023

Abstract
Chronic alcohol consumption is associated with increased risk of gastrointestinal cancer. High concentrations of ethanol trigger mucosal hyperregeneration, disrupt cell adhesion, and increase the sensitivity to carcinogens. Most of these effects are thought to be mediated by acetaldehyde, a genotoxic metabolite produced from ethanol by alcohol dehydrogenases. Here, we studied the role of low ethanol concentrations, more likely to mimic those found in the intestine in vivo, and used intestinal cells lacking alcohol dehydrogenase to identify the acetaldehyde-independent biological effects of ethanol. Under these conditions, ethanol did not stimulate the proliferation of nonconfluent cells, but significantly increased maximal cell density. Incorporation of phosphatidylethanol, produced from ethanol by phospholipase D, was instrumental to this effect. Phosphatidylethanol accumulation induced claudin-1 endocytosis and disrupted the claudin-1/ZO-1 association. The resulting nuclear translocation of ZONAB was shown to mediate the cell density increase in ethanol-treated cells. In vivo, incorporation of phosphatidylethanol and nuclear translocation of ZONAB correlated with increased proliferation in the colonic epithelium of ethanol-fed mice and in adenomas of chronic alcoholics. Our results show that phosphatidylethanol accumulation after chronic ethanol exposure disrupts signals that normally restrict proliferation in highly confluent intestinal cells, thus facilitating abnormal intestinal cell proliferation. (Mol Cancer Res 2007;5(11):1147–57)
Data from NR0B1 Is Required for the Oncogenic Phenotype Mediated by EWS/FLI in Ewing's Sarcoma
Authors: Kinsey Michelle , Smith Richard , Lessnick Stephen L.
Published: April 2023

Abstract
A number of solid tumors, such as alveolar rhabdomyosarcoma, synovial sarcoma, and myxoid liposarcoma, are associated with recurrent translocation events that encode fusion proteins. Ewing's sarcoma is a pediatric tumor that serves as a prototype for this tumor class. Ewing's sarcomas usually harbor the (11;22)(q24;q12) translocation. The t(11;22) encodes the EWS/FLI fusion oncoprotein. EWS/FLI functions as an aberrant transcription factor, but the key target genes that are involved in oncogenesis are largely unknown. Although some target genes have been defined, many of these have been identified in heterologous model systems with uncertain relevance to the human disease. To understand the function of EWS/FLI and its targets in a more clinically relevant system, we used retroviral-mediated RNAi to “knock-down” the fusion protein in patient-derived Ewing's sarcoma cell lines. By combining transcriptional profiling data from three of these lines, we identified a conserved transcriptional response to EWS/FLI. The gene that was most reproducibly up-regulated by EWS/FLI was NR0B1. NR0B1 is a developmentally important orphan nuclear receptor with no previously defined role in oncogenesis. We validated NR0B1 as an EWS/FLI-dysregulated gene and confirmed its expression in primary human tumor samples. Functional studies revealed that ongoing NR0B1 expression is required for the transformed phenotype of Ewing's sarcoma. These studies define a new role for NR0B1 in oncogenic transformation and emphasize the utility of analyzing the function of EWS/FLI in Ewing's sarcoma cells. (Mol Cancer Res 2006;4(11):851–7)
Data from Molecular Characterization of the Transition to Malignancy in a Genetically Engineered Mouse-Based Model of Ductal Carcinoma In situ1
Authors: Namba Ruria , Maglione Jeannie E. , Young Lawrence J.T. , Borowsky Alexander D. , Cardiff Robert D. , MacLeod Carol L. , Gregg Jeffrey P.
Published: April 2023

Abstract
A transplantable model of human ductal carcinoma in situ that progresses to invasive carcinoma was developed from a genetically engineered mouse (GEM). Additional lines were established using early mammary premalignant lesions from transgenic MMTV-PyV-mT mice. These lines were verified to be premalignant and transplanted repeatedly to establish stable and predictable properties. Here, we report the first in-depth molecular analysis of neoplastic progression occurring in one premalignant transplantable GEM-derived line. Oligonucleotide microarrays showed that many genes are differentially expressed between the quiescent and prelactating mammary gland and the premalignant GEM outgrowth. In contrast, a small but consistent group of genes was associated with the transformation from premalignancy to tumor. This suggests that the majority of gene expression changes occur during the premalignant transition from normal to premalignancy, whereas many fewer changes occur during the malignant transition from premalignancy to invasive carcinoma. The premalignant transition is associated with several cell cycle–related genes and the up-regulation of oncogenes is associated with various cancers (Ccnd11, Cdk4, Myb, and Ect2). The changes identified in the malignant transition included genes previously associated with human breast cancer progression. Misregulation of the insulin-like growth factor and transforming growth factor-β signaling pathways and the stromal-epithelial interaction were implicated. Our results suggest that this transplantable GEM-based model recapitulates human ductal carcinoma in situ at both histologic and molecular levels. With consistent tumor latency and molecular profiles, this model provides an experimental platform that can be used to assess functional genomics and molecular pharmacology and to test promising chemoprevention strategies.
Perspective on this Article from Epidermal Growth Factor Receptor Abnormalities in the Pathogenesis and Progression of Lung Adenocarcinomas
Authors: Tang Ximing , Varella-Garcia Marileila , Xavier Ana C. , Massarelli Erminia , Ozburn Natalie , Moran Cesar , Wistuba Ignacio I.
Published: April 2023

Perspective on this Article from Epidermal Growth Factor Receptor Abnormalities in the Pathogenesis and Progression of Lung Adenocarcinomas
Supplementary Table 1 from Identification of Genes Correlated with Early-Stage Bladder Cancer Progression
Authors: Stone Randolph , Sabichi Anita L. , Gill Jennifer , Lee I-ling , Adegboyega Patrick , Dai Michael S. , Loganantharaj Raja , Trutschl Marjan , Cvek Urska , Clifford John L.
Published: April 2023

Supplementary Table 1 from Identification of Genes Correlated with Early-Stage Bladder Cancer Progression
Supplementary Figure 3 from Inhibition of 15-Hydroxyprostaglandin Dehydrogenase by Helicobacter pylori in Human Gastric Carcinogenesis
Authors: Ryu Yeon-Mi , Myung Seung-Jae , Park Young Soo , Yang Dong-Hoon , Song Ho June , Jeong Jin-Yong , Lee Sun Mi , Song Miyeoun , Kim Do Hoon , Lee Hyo-Jeong , Park Soo-Kyung , Fink Stephen P. , Markowitz Sandy D. , Jung Kee Wook , Kim Kyung-Jo , Ye Byong Duk , Byeon Jeong-Sik , Jung Hwoon-Yong , Yang Suk-Kyun , Kim Jin-Ho
Published: April 2023

PDF file - 1329K, MAPK signaling pathway activated by H pylori
Data from Epidermal Growth Factor Receptor Abnormalities in the Pathogenesis and Progression of Lung Adenocarcinomas
Authors: Tang Ximing , Varella-Garcia Marileila , Xavier Ana C. , Massarelli Erminia , Ozburn Natalie , Moran Cesar , Wistuba Ignacio I.
Published: April 2023

Abstract
To identify the characteristics and sequence of epidermal growth factor receptor (EGFR) abnormalities relevant to the pathogenesis and progression of lung adenocarcinoma, we performed a precise mapping analysis of EGFR mutation, gene copy number, and total and phosphorylated EGFR protein expression for the same tissue sites. We examined normal bronchial and bronchiolar epithelium (NBE) and tumor tissues obtained from 50 formalin-fixed lung adenocarcinomas, including 24 EGFR-mutant primary tumors with nine corresponding lymph node metastases and 26 wild-type primary tumors. NBE in 12 of 24 (50%) mutant and 3 of 26 (12%) wild-type tumors harbored EGFR mutations; these NBE also showed a lack of EGFR copy number increase and frequent EGFR (69%) and phosphorylated EGFR (33%) overexpression. EGFR mutation and protein overexpression were more frequent in NBE sites within tumors than in NBE sites adjacent to and distant from tumors, suggesting a localized field effect. Sites with high and low EGFR copy numbers were heterogeneously distributed in six of nine primary tumors and in one of eight metastases. EGFR protein overexpression was significantly higher in metastasis sites than in primary tumors. We conclude from our findings that EGFR mutations and protein overexpression are early phenomena in the pathogenesis of lung adenocarcinoma and that EGFR mutation precedes an increase in gene copy number. In EGFR-mutant adenocarcinoma metastases, the higher levels of EGFR overexpression and more homogeneously distributed high gene copy numbers suggest tumor progression. Our findings have important implications for the development of new strategies for targeted chemoprevention and therapy in lung adenocarcinoma using EGFR inhibitors.
Data from Linking Epidemiology to Epigenomics—Where Are We Today?
Authors: Ulrich Cornelia M. , Grady William M.
Published: April 2023

Abstract
Cancer is the consequence of genetic and epigenetic alterations. Genetic mutations likely result in part from exposure to environmental carcinogens, giving rise to a large field of cancer-prevention study of these carcinogens and ways to develop strategies to avoid them. Our understanding of regulatory epigenetic mechanisms associated with DNA methylation, histone modifications, and microRNA production is increasing rapidly. The involvement of these processes in carcinogenesis raises the possibility that environmental exposures may promote or prevent cancer through affecting the epigenome. Modifying the epigenome to prevent cancer is particularly intriguing because epigenetic alterations are potentially reversible, unlike gene mutations, and because certain dietary factors, such as the B-vitamin folate, may affect genes' DNA methylation status (as reported by Wallace et al., beginning on page 1552 in this issue of the journal). Rapidly improving techniques for assessing epigenetic alterations promise to yield important insights for cancer prevention. Cancer Prev Res; 3(12); 1505–8. ©2010 AACR.
Data from Inhibition of 15-Hydroxyprostaglandin Dehydrogenase by Helicobacter pylori in Human Gastric Carcinogenesis
Authors: Ryu Yeon-Mi , Myung Seung-Jae , Park Young Soo , Yang Dong-Hoon , Song Ho June , Jeong Jin-Yong , Lee Sun Mi , Song Miyeoun , Kim Do Hoon , Lee Hyo-Jeong , Park Soo-Kyung , Fink Stephen P. , Markowitz Sandy D. , Jung Kee Wook , Kim Kyung-Jo , Ye Byong Duk , Byeon Jeong-Sik , Jung Hwoon-Yong , Yang Suk-Kyun , Kim Jin-Ho
Published: April 2023

Abstract
Helicobacter pylori (H. pylori) infection induces a chronic inflammatory response, which promotes gastric carcinogenesis. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) plays a key role as a tumor suppressor in gastrointestinal cancers. The aim of this study was to elucidate the role of 15-PGDH in gastric carcinogenesis associated with H. pylori. 15-PGDH expression in gastric biopsies from H. pylori–infected (n = 25) and noninfected (n = 15) subjects was analyzed by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. 15-PGDH DNA methylation was evaluated by methylation-specific PCR and pyrosequencing. The expression of 15-PGDH, Snail, extracellular signal–regulated kinase (ERK)1/2, TLR4, and MyD88 in response to H. pylori infection was assessed by immunoblot analysis. Compared with negative specimens, H. pylori–positive specimens had 2-fold lower 15-PGDH mRNA levels and significantly less 15-PGDH protein. In four H. pylori–infected subjects with longitudinal follow-up, the suppression of 15-PGDH expression was reversed by H. pylori eradication therapy. In parallel with suppressing 15-PGDH expression, H. pylori infection activated expression of TLR4 and MyD88 expression, increased levels of phospho-ERK1/2, and increased expression of EGF receptor (EGFR)-Snail. Inhibition of Snail and MyD88 reversed suppression of 15-PGDH expression, and siMyD88 reduced phosphorylated ERK1/2. Similarly, treatment with an ERK1/2 and EGFR inhibitor also restored 15-PGDH expression. H. pylori appeared to promote gastric carcinogenesis by suppressing15-PGDH. This process is mediated by the TLR4/MyD88 pathway via ERK1/2 or EGFR-Snail transcriptional regulation. 15-PGDH may be a useful marker and a potential therapeutic target in H. pylori–induced gastric carcinogenesis. Cancer Prev Res; 6(4); 349–59. ©2013 AACR.
Childhood Cancer Treatment and Clonal Hematopoiesis
Authors: Collord Grace , Behjati Sam
Published: April 2023

Hagiwara and colleagues investigated the effects of childhood cancer treatment on the clonal composition of blood. Their findings provide strong evidence that treatment promotes clonal outgrowths (clonal hematopoiesis) in childhood cancer survivors.

See related article by Hagiwara et al., p. 844 (4).
How Can I Trust You? The Role of Facial Trustworthiness in the Development of Epistemic and Interpersonal Trust
Authors: Milesi Alberto , De Carli Pietro , Locati Francesca , Benzi Ilaria M.A. , Campbell Chloe , Fonagy Peter , Parolin Laura
Published: April 2023

Recently, researchers from developmental and clinical psychology highlighted epistemic trust (ET) as a key factor for personality disorders. ET is intended as the mental openness to information coming from others during social exchanges. ET develops from signals called ostensive cues, delivered through facial expressions during interactions in a secure attachment context. Similarly, interpersonal trust (IT) refers to the perception of others as not harmful, which is also developed through secure attachment relationships. Our purpose was to suggest a conceptualization of ET as a specific facet of IT. We hypothesize that positive experiences of caregiving promote IT development that includes a specific sense of trust toward others’ knowledge. Moreover, we suggest that the early ability to infer a judgment of trustworthiness from facial cues is the starting point for developing both IT and ET. This conceptualization supports the role of considering both IT and ET in the development of borderline pathology.
Hanseníase na Amazônia central: um olhar epidemiológico
Authors: Ferreira Luan Moraes , Souza Yasmin Azevedo de , Batista Gisela Gomes , Vieira Camila Paranhos , Nunes Cleizimara Cavalcante , Magalhães Letícia Santana , Silva Ícaro Breno Rodrigues da , Lima Vanessa Kemilly Gomes , Martins Nádia Vicência Nascimento
Published: April 2023

OBJETIVO: Descrever a epidemiologia e o perfil clínico da hanseníase na região oeste do estado do Pará, Brasil, no período de 2014 a 2020. MÉTODO: Trata-se de um estudo de corte transversal, descritivo. A coleta de dados foi realizada a partir do Sistema de Informação de Agravos de Notificação (SINAN) da Secretaria de Vigilância em Saúde (SVS) do Ministério da Saúde do Brasil no período de junho de 2021 a agosto de 2021, e uma revisão da literatura na base dados PUBMED. RESULTADOS: Foram registrados 1764 casos, com uma prevalência de 17,5 por 10.000 habitantes, sendo 942 (53,5%) na região do Tapajós e 822 (47,9%) na região do Baixo Amazonas. Houve predomínio na faixa etária de 40 a 49 anos (20,6%); cor “parda” (73,6%); escolaridade com Ensino Fundamental Incompleto (55,7%); sexo masculino (66,3%); forma clínica Dimorfa (54,5%); classificação operacional Multibacilar (82,3%); grau zero de incapacidade funcional (41,6%); episódios reacionais tipo I (11,6%). Na revisão de literatura, foram incluídos 9 artigos após aplicação dos critérios de inclusão e exclusão e leitura dos artigos na íntegra. CONCLUSÃO: Houve redução no número de casos de hanseníase na Mesorregião no período estudado. Todavia, ainda existem déficits nas estratégias de rastreio, tratamento e acompanhamento dos casos de hanseníase, com prevalência de casos altamente transmissíveis e clinicamente graves, especialmente entre homens em idade economicamente ativa. Dessa forma, faz-se essencial a adoção de políticas públicas regionais para combate, controle e prevenção da hanseníase na região Oeste do estado do Pará.
Prevalência de trombose coronariana após angioplastia primária em pacientes com infarto agudo de miocárdio e COVID-19: uma revisão bibliográfica
Authors: Agostinete Sandy Parreira , El Sabbagh Clara Pechmann Mendonça , Carmo Adriana Boiteux do , Sobral Marcelo Luiz Peixoto
Published: April 2023

Introdução: A COVID-19 é causada pelo coronavírus da síndrome respiratória aguda grave (SARS-CoV-2) e os indivíduos com maior probabilidade de apresentarem sintomas mais graves são idosos com comorbidades como: diabetes, doenças cardiovasculares, câncer e histórico de tabagismo. Esta doença cursa com liberação de mediadores inflamatórios e ateroscleróticos, gerando a instalação do estado hipercoagulável, o que levanta a possibilidade de risco aumentado para síndromes coronárias agudas e trombose coronariana pós angioplastia primária. Objetivo: Avaliar a prevalência de trombose coronariana após angioplastia primária em pacientes com infarto agudo de miocárdio infectados pela COVID-19. Material e métodos: Trata-se de uma pesquisa bibliográfica do tipo revisão de literatura tendo como base produções científi-cas publicadas nas seguintes bases de dados: PubMed, Medline, SciELO, NCBI e Lilacs. Resultados: Quanto a técnica de revascularização a ser escolhida temos que, a angioplastia primária é utilizada como principal estratégia para redução de danos, melhor desfecho e preservação da função ventricular, na doença cardíaca isquêmica aguda. Entretanto, a incidência de eventos tromboembólicos é extremamente alta em pacientes com infarto agudo do miocárdio com supra de ST infectados com o SARS-Cov-2 submetidos à angioplastia primária, de acordo com alguns estudos. Conclusão: Há maior prevalência de trombose coronariana em pacientes com infarto agudo do miocárdio com supra de ST infectados com o SARS-Cov-2 após serem submetidos à angioplastia primária.
Lesões iatrogênicas das vias biliares: diagnóstico e manejo
Authors: Fonseca Neto Olival Cirilo Lucena da , Perez Mateus Interaminense , Lopes Vladmir Goldstein de Paula
Published: April 2023

A lesão iatrogênica das vias biliares (LIVB) se configura em uma grave complicação relacionada a abordagens cirúrgicas do trato gastrointestinal e mesmo em centros de referência taxas de 0,2% a 1,5% ainda são registradas. A taxa de LIVB varia se a cirurgia inicial foi realizada por meio de técnica aberta ou videolaparoscópica, e a sua gravidade se dá pelo grande espectro de complicações que podem ser causadas e que apresentam forte impacto negativo na qualidade de vida do paciente. A primeira classificação de LIVB se deu em 1982 com Bismuth e, com o advento da videolaparoscopia, várias outras foram feitas, sendo a de Strasberg uma das mais utilizadas até hoje. A suspeição diagnóstica pode ser feita com auxílio de exames laboratoriais e principalmente com exames de imagem, como a colangiorressonância. O tratamento se constitui em um verdadeiro desafio para a equipe cirúrgica e pode ser realizado por meio de técnicas percutâneas endoscópicas e também cirúrgicas, sendo mais comumente realizada por meio de hepaticojejunostomia em Y de Roux. No paciente com doença hepática em estágio terminal por cirrose biliar secundária, pode ser realizado o transplante hepático. O paciente sempre que possível deve ser acompanhado por uma equipe multidisciplinar e é de suma importância que seja rapidamente encaminhado para um centro especializado.
Hiperparatireoidismo associado a hipercalciúria primária em paciente apresentando litíase renal recorrente
Authors: Pigosssi Beatriz D'Andrea , Pedroso Igor Queiroz , Mattos Lígia Oliveira , Dias João Carlos Ramos , D’Avila Ronaldo
Published: April 2023

A litíase urinária acomete 5 a 10% da população brasileira e têm uma taxa de recidiva após a primeira crise de até 50% em cinco a dez anos. A hipercalciúria é a mais frequente alteração metabólica encontrada nesses pacientes com cálculos renais e pode ser caracterizada de três formas: (1) absortiva (intestinal), (2) renal e (3) reabsortiva (óssea). OBJETIVO: Descrever o caso de uma paciente com nefrolitíase de repetição associada a hipercalciúria e discutir sobre a associação com hiperparatireoidismo secundário. MATERIAIS E MÉTODOS: As informações foram obtidas por meio de revisão do prontuário, entrevista com o paciente, registro fotográfico dos métodos diagnósticos aos quais a paciente foi submetida e revisão da literatura. CONCLUSÃO: Calculoses causadas por hipercalciúria primária sustentada podem causar hiperparatireoidismo secundário à hipocalcemia, de forma a ser necessário diagnóstico diferencial com hiperparatireoidismo primário e outras causas de hiperparatireoidismo secundário.
Hanseníase em uma região semiárida da Bahia: uma análise de 2001 a 2017
Authors: Lima Iara Ferreira de , Braga Isaque Oliveira , Melo Isnaia Firminia de Sousa Almeida Agostinho de , Nery Joilda Silva , Takenami Iukary Oliveira , Tenório Pedro Pereira
Published: April 2023

Objetivo: Avaliar o perfil clínico-epidemiológico dos casos de hanseníase em uma região semiárida da Bahia. Método: Trata-se de um estudo corte transversal, realizado a partir de dados de 167 prontuários de pacientes diagnosticados com hanseníase e atendidos em uma Unidade de Saúde da Família em Paulo Afonso, Bahia, no período de 2001 a 2017. Resultados: A taxa anual de detecção de casos novos foi 9 por 100 mil habitantes. Dos 167 pacientes, 111 (66,5%) eram do sexo feminino; 49 (29,3%) tinham entre de 31 e 45 anos. A proporção de casos com menos de 15 anos foi de 10,8%. A hanseníase tuberculóide foi a forma mais comum (55,1%) e a proporção de hanseníase paucibacilar foi de 64,1%. Comparada à classificação operacional, a forma clínica demonstrou 94,9% de acerto e uma concordância quase perfeita (κ = 0,888). Efeitos adversos foram relatados em 25 (15%) pacientes com hanseníase. Conclusão: Casos de hanseníase têm sido notificados em Paulo Afonso, tornando o município uma área de média endemicidade. O fortalecimento das medidas de controle da hanseníase deve ser priorizado para eliminar a doença nesta região.
Application of the methodology “Diagnostics of the mental development of children from birth to three years” in clinical psychology and psychiatry
Authors: Trushkina Svetlana V. , Skoblo Galina V.
Published: April 2023

Background. Ye methodology “Diagnostics of the mental development of children from birth to 3 years” was developed by the team of authors under the guidance of E.O. Smirnova. Ye methodology is aimed at determining the levels of development of communication, objective activity and play in infants and young children. Ye experimental nature of the examination procedure and the innovative system of diagnostic parameters, which is interdisciplinary in its nature, determines the interest in it among clinical psychologists and psychiatrists. Objective. Ye study is meant to assess the possibilities of using the methodology “Diagnosis …” in clinical psychology and psychiatry, as well as to outline the ways to adapt it to the peculiarities of clinical-psychological and psychiatric examination for children at early and preschool age. Method. Ye study involved children of early and preschool age with veriZed psychiatric diagnoses. Ye data were obtained through observation of communication, objective activity and play of children during examination with the “Diagnostics …” method and during psychiatric and clinical-psychological examination. Ye article presents the qualitative results of the study and their analysis. Results. It was shown that the technique is e[ective in psychiatric and clinical-psychological examination of children and allows to obtain data that are highly informative and novel. Yis applies to the parameters of child’s development: initiative and sensitivity in communication, purposefulness of activities, the desire to act according to the model, orientation to the assessment by an adult, speech accompaniment of activities, duration of game, variety of playing actions, imagination, etc. Ye study also showed that the technique proves to be e[ective beyond an early age for children, su[ering from mental disorders. Conclusion. Ye results obtained allow us to consider the technique as an adequate tool not only for psychological and pedagogical, but also for clinical-psychological and medical research. At the same time, it is necessary to conduct additional interdisciplinary research in order to adapt this technique for the purposes of scientiZc and practical application in clinical psychology and psychiatry.
Німецькі форми назви слюсаря у польській та східнослов’янських мовах
Authors: Пиц [Pyts] Тарас [Taras]
Published: April 2023

The Names for a Locksmith in German, Polish and East Slavic Languages This article analyses the names for a locksmith in German, Polish, Ukrainian and Belarusian. The paper outlines previous explorations in this respect and identifies their shortcomings. The author presents the distribution of the forms under study in different groups of German dialects between the thirteenth and sixteenth centuries and traces their origins. He also discusses their orthographic, phonetic and morphological assimilation in the Slavic languages. The analysis of historical and linguistic sources has made it possible to identify selected phonetic and morphological processes which occurred in German and are visible in Polish, Ukrainian and Belarusian.Nazwy ślusarza w języku niemieckim, polskim i językach wschodniosłowiańskichNiniejszy artykuł jest poświęcony analizie nazwy ślusarz w językach: niemieckim, polskim, ukraińskim i białoruskim. Opracowanie przedstawia dotychczasowe badania w tym zakresie i wskazuje ich niedociągnięcia. Autor opisuje dystrybucję badanych form w różnych grupach dialektów języka niemieckiego od XIII do XVI wieku oraz ustala ich pochodzenie. Następnie omawia ich ortograficzną, fonetyczną i morfologiczną asymilację w językach słowiańskich. Analiza źródeł historycznojęzykowych pozwoliła zidentyfikować wybrane procesy fonetyczne i morfologiczne, które zaszły w języku niemieckim i są widoczne w językach: polskim, ukraińskim i białoruskim.
A Novel Exon 2 Deletion Mutation in the GRXCR1 Gene Associated With Non-Syndromic Hearing Loss: A Case Report and Review of Literatures
Authors: Rastad Hadith , Samimisedeh Parham , Savad Shahram , Seifi Alan Mahnaz
Published: April 2023

Background:

About 80% of congenital hearing loss cases have genetic causes, often autosomal recessive and non-syndromic. Autosomal Recessive Non-syndromic hearing loss is characterized by extreme genetic heterogeneity.

Objectives:

To report a case of congenital hearing loss with novel homozygous deletion in GRXCR1 gene.

Methods:

Case reports and review of literatures.

Results:

In this study, the proband was a 32-year-old woman seeking pre-marriage genetic counseling with non-syndromic congenital hearing loss. An owing negative test for GJB2 mutations, she underwent exome sequencing, unveiling a novel homozygous exon 2 deletion of the GRXCR1 gene. This mutation was confirmed in her affected mother and sibling by PCR and Quantitative Real-Time PCR.

Conclusion:

We identified a novel GRXCR1 gene mutation related to congenital hearing loss in a family. Our study highlights the efficiency of exome sequencing in discovering gene mutations in cases of diseases with genetic heterogeneity.
Beating the Gun—One Conversation at a Time? Evaluating the Impact of DC’s “Cure the Streets” Public Health Intervention Against Gun Violence
Authors: Chwalisz Natalie
Published: April 2023

Violence interrupters (VI) operate as mediators after gang-involved shootings to stop retributory shootings. While some cities, like Chicago, have seen initial success, other cities, such as Boston, Newark, and Phoenix have seen little or mixed effects. This is the first evaluation of the Washington DC intervention. I use an interrupted time series model to measure the impact the intervention had on the rates of assaults with a gun using DC Crime Incident data. Recognizing that the Covid-19 pandemic is an important confounding event, I also run two time-series control models, a location control, and an outcome control. My findings indicate that the program was not effective in reducing gun violence.
Beyond Ransom and Political Concessions? Explaining Changes in Insurgents’ Kidnapping Involvement Versus Event-frequency
Authors: Liu Lu , Eisner Manuel
Published: April 2023

Kidnapping is a common tactic used by insurgent groups. However, why insurgents commit kidnappings remains insufficiently understood. Based on 1,386 group-year observations of 140 insurgents between 1998 and 2012, we analyze conditions driving the within-group temporal changes in their involvement (1 vs 0) versus event-frequency in kidnappings. We find that changes in specific quasi-state activities (i.e., extraction and provision of public services), which may rely on kidnappings for coercive enforcement and social control, predict kidnapping “involvement” only. Meanwhile, general resource and capacity conditions (i.e., territory-control, criminal networks and combat-lethality) influence changes in both kidnapping involvement and event-frequency.
Transforming schools and improving outcomes for boys of color
Authors: Villavicencio Adriana
Published: April 2023

Since the early 1980s, young women have outpaced men in educational outcomes. The gender gap is even more pronounced among Black and Latinx students. Moreover, these academic gaps have widened since the pandemic. Based on a five-year study of a district-wide initiative designed to improve academic outcomes for Black and Latino males, Adriana Villavicencio lays out a three-pronged approach to supporting the socioemotional well-being and academic success of young men of color through 1) culturally relevant classrooms, 2) improved school relationships, and 3) robust academic and college preparation.
Boys and the humanities: Making the twain meet
Authors: Spitsberg Tim , Plucker Jonathan A.
Published: April 2023

Misalignment between the mandates and structures of formal schooling and the developmental needs of boys, particularly in the humanities, is receiving increased levels of public and scholarly attention. The problems may be especially acute for low-income and minoritized children. But little guidance for identifying and implementing best and promising practices is available for educators. Tim Spitsberg and Jonathan A. Plucker outline recent work on this problem and identify some promising state- and local-level strategies for beginning the hard work of improving humanities learning for boys. They advocate pairing common-sense policy and curricular changes (improved data-sharing, curricular reviews for gender bias) with research-supported interventions (personalization, pathways programs into humanities-based learning and professions). When implemented with care, these strategies could improve the education of all students.
The need for Black male mentors
Authors: Rodgers Bobby J. , Rodgers Devery J.
Published: April 2023

The academic achievement of Black boys in the U.S. has been declining, and Black male mentorship can positively change these outcomes. Schools have tried many interventions to help Black boys receive the academic, social, and emotional support they need to close the performance gap. Some case studies have proven that Black male mentorship works. Bobby J. Rodgers Jr. and Devery J. Rodgers examine Black male student academic performance and propose Black male mentoring as a solution that offers promise in closing the performance gap.
Rethinking school time
Authors: Hess Frederick M.
Published: April 2023

Efforts to improve education outcomes often involve lengthening the school day or the school year in hopes that spending more time in school will boost student learning. Yet, as Frederick Hess explains, U.S. students spend as much or more total time in school as their peers in other industrialized nations. What matters more than the amount of time is how that time is used. Although research into time usage at school is limited, existing studies have shown that much time spent in school time does not involve actual learning time, either because of interruptions or other non-learning activities or because students are not engaged. Hess suggests that, before adding time to the school day or year, it’s important to understand what schools are doing with their time, rethink their routines, and seek to ensure that they are using time wisely and well.