tbuckley/cabot-search huggingface dataset:
Heregulin induces Iressa-resistance of breast cancer cells through receptor heterodimerization.
Authors: J Li, H Liu, I Espinoza, R Lupu
Journal: Cancer Research (2009)

Abstract Abstract #2016 Background: Heregulins (HRGs) are known as soluble secreted growth factors that are involved via binding and activating HER3 and HER4 cell surface receptors in cell proliferation, metastasis, survival, and differentiation in normal and malignant tissues. We have previously shown that up-regulation of HRG is sufficient for development of mammary tumors independently of estrogen stimulation and HER2 overexpression. Moreover, inhibition of HRG expression suppresses the aggressive phenotype by decreasing HER activation and reducing matrix metalloproteinase-9 activity. Therefore, HRG appears to be a key modulator of tumorigenicity and metastasis in triple negative breast carcinomas. Resistance to anti-epidermal growth factor receptor (anti-EGFR) therapies such as gefitinib is an emerging clinical problem. In this regard we have used MDA231, HS578T and BT549 cells to study potential mechanisms of gefitinib resistance. These cell lines are EGF independent and express high levels of HRG and resistant to gefitinib. Our hypothesis is that HRG signaling through HER3 induces resistance to EGFR blockade. To demonstrate this, we knocked down HRG expression by RNA interference (RNAi) in MDA231, HS578T, and BT549 cells.&amp;#x2028; Material and Methods: Down-regulation of HRG is observed in MDA231, HS578T, and BT549 cells transduced with HRG siRNA lentiviral vector pRNAt-U6.2. Sensitivity to gefitinib was determined by MTT assays and soft agar assays. Each experiment was repeated at least 3 times, all data were analyzed by ANOVA. The level of significance was set at p &amp;lt; 0.05.&amp;#x2028; Results: Our results show that when comparing to their parental cells, all MDA231/HRGsiRNA, HS578T/HRGsiRNA and BT549/HRGsiRNA cells grew at a lower rate and become sensitive to gefitinib. Our results indicate that HRG can overcome the inhibitory effects of gefitinib on cell growth and HRG signaling allows at least in part, the acquisition of gefitinib-resistant phenotype.&amp;#x2028; Discussion: Although the mechanism for the resistance is still under further investigation, our observation has implications for the effectiveness of anti-EGFR therapies in breast cancer where HRG induced receptor heterodimerization in EGFR-positive breast tumors. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2016.
Abstract 4251: Genomewide methylation and expression profiles in cervical cancer.
Authors: Kwon Yongil, Nakwoo Lee, Sungjong Lee
Journal: Cancer Research (2013)

Abstract Cervical carcinoma is one of the most common cancers in females. This cancer begins with precancerous stages and can evolves to carcinoma over 10 years or more. Cervical cancer is a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes. We aimed to identify genetic alterations associated with pre-cancerous stage and also with cervical cancer. For this purpose, microarray comparative genomic hybridization(Illumina 450K and Illumina Expression HT12 Human CGH Whole-Genome Arrays) was performed with 16 cases of cervical intraepithelial neoplasia(CIN) of different stages and 3 cases of carcinoma. We identified epigenetic inactivation of TSGs by hyper- or hypo-methylation which has been recognized as an important and alternative mechanism in tumorigenesis. Here we discuss these epigenetic alterations in cervical intrapeithelial neoplasia and cervical cancer focusing on DNA methylation. Citation Format: Kwon Yongil, Nakwoo Lee, Sungjong Lee. Genomewide methylation and expression profiles in cervical cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4251. doi:10.1158/1538-7445.AM2013-4251
Nodular Goiter and Thyroid Cancer
Authors: Thomas J. Anglem, Martin L. Bradford
Journal: New England Journal of Medicine (1948)

IN THE therapeutic attack on malignant tumors in general, the accumulated experience of generations has established as virtually axiomatic certain well defined principles.The first is the folly of attempting to arrive at a diagnosis by observation of the continued growth of a tumor or area of nodularity until its malignant nature is clear and unmistakable. As stated by Taylor,1 one must answer the question, "What is the disease?" It must be answered early, by biopsy or by removal of the lesion in question.A second is the great utility of the principle of prophylactic removal of lesions that, though . . .
THU0367 Joint echinococcosis: A report of three new cases
Authors: W. Hamdi, M.M. Ghannouchi, M. Bouaziz, F.M. Ladeb, M.M. Kchir
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Joint hydatidosis is defined as the development within the joint of multiple cysts that are the larval form of the tapeworm echinococcus granulosus. Bone and joint cysts account for less than 0.5% of all hydatid cysts in human. We report three cases of joint hydatidosis. <h3>Results</h3> Case 1: A 63-year-old woman, who was operated 4 times for lung and liver cyst hydatidosis, was complaining of right inflammatory lumbosciatica S1. Examination revealed pain when pressing the sacral region. X-rays revealed a heterogeneous lesion of the right sacrum. Computed tomography showed an eleven-mm diameter cyst in the right buttock joint with an anterior development into the pelvic cavity. Muscles were not involved. Surgical enucleation of the cysts was performed. Histopathologic examination showed germinative membranes of the hydatid cyst confirming the diagnosis. Case 2: A 35 year old man with history of right hip pain for the past 5 years and a progressive loss of motion range. Examination found a painful and restricted right hip movement in all directions. X-rays and computed tomography scan showed bone destruction of the hip, multiple cysts and ectopic calcifications around the joint. Serological test for hydatid disease was positive (1/280), confirming the diagnosis of hip hydatidosis. Case 3: A 39 year old women with history of liver hydatid cyst treated with surgery 14 years ago, was complaining of right shoulder pain for the past year. Examination revealed diffuse swelling of right shoulder with painful and restricted movement in all directions. X-rays showed multiple cysts of the shoulder with pathological fracture of the humerus diaphysis. MRI and hydatid serological test confirmed the diagnosis. <h3>Conclusions</h3> Hydatid cysts still occur in Tunisia despite prevention programs. The liver and the lung are the most frequent targets. The joint involvement is uncommon but severe. Joint contamination is usually local from bone lesion and rarely by blood or lymph vessels. Surgical excision of cysts is the main treatment but recurrence is possible particularly at proximal joint that are difficult to access. <h3>Disclosure of Interest</h3> None Declared
THE EFFECTS OF AN ELECTRONIC MEDICAL RECORD ON DUPLICATE TESTING: A STUDY OF 18,000 TRANSTHORACIC ECHOCARDIOGRAMS
Authors: Azriel Avezbadalov, Charles A. Cevallos, Joshua R. Gildin, Simcha Pollack, Arnoux Blanchard, Michael A. Chizner
Journal: Journal of the American College of Cardiology (2016)
Immunosuppressive DX5+ T cells are potent inhibitors of Th-1 responses via modulation of DCs
Authors: Hanane el Bannoudi, Wanda G H Han, Jeroen Stoop, Pascale Louis-Plence, Tom W J Huizinga, René E M Toes
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> DX5+CD4+ T cells have been shown to have both a protective- and therapeutic effect on collagen-induced arthritis. This protective effect was associated with an increase in IL-10 production. To understand the mechanisms used by DX5+ T cells to dampen Th1-associated inflammation in CIA, the authors recently studied their immunomodulatory action on CD4+ T cells. These studies revealed that these cells are very effective in modulating Th1-cell responses through direct effects on CD4+ T cells by production of IL-4. In the presence of DX5+ T cells, IFNγ production was inhibited whereas IL-10 secretion was induced in responding CD4+ T cells. To further define additional mechanisms applied by DX5+ T cells to inhibit Th1-immunity, the authors studied the effects of DX5+ T cells on DC function. <h3>Materials and methods</h3> D011.10 (OVA specific TCR Tg) mice were used for the generation of bone marrow DCs (BMDCs) and for the isolation of CD4+ T cells. BMDCs were cultured with DX5+ or DX5- supernatants for 3 days. LPS was added after 1 day of incubation. The DCs obtained were cultured at 0.4×106/ml with OVA323–339 peptide and OVA specific CD4+ T at 1×106/ml in total volume of 150 µl for 3 days. At day 3, the secretion of cytokines was determined by flow cytometry. 12p70 levels in BMDCs cell culture supernatants were measured by ELISA. <h3>Results</h3> The authors demonstrate that DX5+ T cells can also indirectly inhibit Th1 responses through modulation of DC. DX5+ T cells robustly inhibit IL-12-production by DC. This effect was dependent on IL-10 produced by DX5+ T cells and does not require cell-cell contact. In addition, DX5+ T cells modulate the surface phenotype of LPS-matured DC as high levels of the "co-inhibitory" molecules PD-L1 and PD-L2 were induced. Importantly, OVA-specific CD4+ T cells primed by DC exposed to DX5+ T cell supernatant produced less IFNγ as compared to their counterparts primed by conventional DC. Addition of IL-12 restored IFNγ production. When IL-10 derived form DX5+ T cells was neutralised, DC re-established their ability to produce IL12 and to efficiently prime Th1 responses. <h3>Conclusion</h3> These data show that DX5+ T cells cannot only directly inhibit Th1-cell immunity, but also indirectly through the modulation of DC.
Methemoglobinemia and Heinz Body Hemolytic Anemia Due to Phenazopyridine Hydrochloride
Authors: Mortimer S. Greenberg, Helena Wong
Journal: New England Journal of Medicine (1964)

THE ability of redox drugs and chemicals to induce hemolytic anemia associated with methemoglobin and the formation of Heinz bodies in red blood cells has long been known,1 and the mechanism of the reaction of such agents on red cells and hemoglobin has recently been described.2 The purposes of this report are to record the occurrence of methemoglobinemia and Heinz-body anemia in patients taking phenazopyridine hydrochloride (phenyl-azo-diaminopyridine hydrochloride), a urinary-tract analgesic, and to describe the effects of this drug on human red cells in vitro.MethodsHematocrits, hemoglobin concentrations and reticulocyte counts were done by standard methods.3 The survival of . . .
Abstract 4634: Decreased infiltration of macrophage scavenger receptor in non-malignant biopsy specimens is associated with detection of prostate cancer
Authors: Hitoshi Takayama, Koji Hatano, Atsunari Kawashima, Masatoshi Mukai, Akira Nagahara, Yasutomo Nakai, Masashi Nakayama, Kazuo Nishimura, Akihiko Okuyama, Norio Nonomura
Journal: Cancer Research (2010)

Abstract INTRODUCTION AND OBJECTIVE: Screening for prostate cancer (PCA) has become widespread practice. Many men with negative biopsy findings undergo repeat biopsies to rule out PCA. It should be long enough to avoid unnecessary biopsies and costs. The discovery of new predictors is essential to establish appropriate repeat biopsies. Several predictors of subsequent PCA detection have been described. Especially, chronic inflammation is considered to be a risk factor for PCA. The macrophage scavenger receptor (MSR) has been reported to play a role in recognizing foreign pathogenic substances. MSR-positive inflammatory cells are often seen in solid tumors. Tumor-associated macrophages (TAM) have been shown to positively or negatively regulate the growth of various malignant cells. However, the role of MSR and TAM in PCA carcinogenesis is unclear. In the present study, infiltration of MSR and TAM in non-malignant biopsy specimens was evaluated as a possible predictive value for PCA. METHODS: These reviews were evaluated for 92 patients ranging from 51 to 82 years (median, 69 years), who received repeat needle biopsies of the prostate and were diagnosed as non-malignant during first biopsy. Of these, 30 (32.6%) were positive for cancer during second or third biopsy. TAM and MSR were immunohistochemically labeled using a monoclonal (CD68 and CD204) antibody. For systematic counting, 6 ocular measuring fields were randomly chosen under a microscope at a power of × 400 within first negative biopsy specimens. RESULTS: There were no significant differences in PSA, Age and Interval of previous and subsequent biopsies, between negative and positive cases for cancer. Median count of MSR and TAM in each case was 32 and 16. MSR count in patients with cancer was lower than in patients without cancer (P &amp;lt; 0.001). However, in TAM count there were no significant differences between patients with or without cancer. CONCLUSION: Decreased infiltration of MSR in non-malignant biopsy is associated with detection of PCA. MSR is predictor for appropriate repeat biopsies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4634.
Abstract 5062: Rac1 signaling is up-regulated in normal tissue adjacent to recurrent respiratory papillomas
Authors: Alexandra V. Lucs, Rong Wu, Marc H. Symons, Allan L. Abramson, Bettie M. Steinberg
Journal: Cancer Research (2010)

Abstract Recurrent respiratory papillomas, caused by human papillomavirus infection, are benign tumors that block the airway and have significant potential for malignant conversion. Previously we have shown that the epidermal growth factor receptor (EGFR) is overexpressed in papillomas. This overexpression leads to the activation of a novel signaling pathway involving increased expression of the Rho-family member GTPase Rac1, activation of the p38 mitogen activated kinase and increased expression of cyclooxygenase 2 (COX-2). This pathway is not activated in normal laryngeal epithelial tissue samples from individuals without the disease, but is constitutively active in papilloma tissue. Here we have investigated the extent to which the EGFR → Rac1 → p38 → COX-2 pathway is activated in clinically normal airway tissue from patients with respiratory papillomas. Surprisingly, we found that the Rac1 and COX-2 levels are comparable in “normal” and papilloma tissues, suggesting widespread activation of this pathway in the laryngeal mucosa, without marked elevation of the EGFR in the “normal” adjacent tissue. Moreover, preliminary data suggests that overexpression of Rac1 in these patients may be systemic, as it is also found at higher levels in peripheral blood mononuclear cells. We hypothesize that Rac1 overexpression may be a rare genetic trait that predisposes these patients to develop recurrent respiratory papillomatosis. Furthermore, investigation into Rac1 levels revealed the presence of a splice variant known as Rac1b. This constitutively active form of Rac1 is found at higher levels in papilloma tissue when compared to “normal” adjacent tissue from the same patient, possibly contributing to the growth of the tumors. Our current research is focused on determining the mechanism of Rac1 overexpression and elucidating the role of the Rac1 isoforms in papilloma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5062.
Abstract 3300: MYC regulation of a “poor prognosis” metastatic cancer cell state
Authors: Anita Wolfer, Ben S. Wittner, Daniel Irimia, Richard J. Flavin, Mathieu Lupien, Ruwanthi N. Gunawardane, Clifford A. Meyer, Eric S. Lightcap, Pablo Tamayo, Jill P. Mesirov, Xiaole S. Liu, Toshihiro Shioda, Mehmet Toner, Massimo Loda, Myles Brown, Joan S. Brugge, Sridhar Ramaswamy
Journal: Cancer Research (2010)

Abstract Gene expression signatures are used clinically as prognostic tools to determine the risk of individual patients with localized breast tumors developing distant metastasis. However, we lack a clear understanding of whether these correlative biomarkers link to a common biological network that regulates metastasis. METHODS: In order to address this question, we analyzed thirteen different well-described (including two in clinical use) “poor outcome” cancer signatures in a cell line model of estrogen receptor positive breast cancer (MCF7) manipulated by diverse oncogenic stimuli. RESULTS: We find that the c-MYC oncoprotein coordinately regulates the expression of these thirteen different “poor outcome” cancer signatures. In addition, functional inactivation of MYC in human breast cancer cells specifically inhibits their distant metastasis in vivo and invasive behavior in vitro. CONCLUSION: These results suggest that MYC oncogene activity, as reflected by “poor prognosis” signature expression, may be necessary for the translocation of “poor outcome” human breast tumors to distant sites. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3300.
OP0261 Genetic and functional evidence for a role of the bone morphogenetic protein type 1B receptor in ankylosis in mice
Authors: S. Carter, I. Derese, K. Braem, F. Luyten, R. Lories
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Progression of ankylosis in patients with <i>ankylosing spondylitis</i> is highly variable, suggesting that ankylosis is at least partially due to genetic factors. We used a murine ankylosing enthesitis mouse model (DBA/1) to search for disease-associated genes and limb bud pellet culture to examine differences in cartilage and bone formation between DBA/1 and BALB/c mice. <h3>Objectives</h3> To study genetic factors that play a role in murine ankylosis and to assess the functional effect of identified genes. <h3>Methods</h3> Male DBA/1 were crossed with female BALB/c mice. At 26 weeks, histomorphology was examined in male F2 mice from different litters. 159 markers with sequence-length polymorphisms on the autosomes were selected, with a median marker spacing of 6.9 cM. 162 F2 male mice were studied. Genes in regions of interests were linked to skeletal development pathways with the Gene Ontology database. Association was evaluated by Chi-square tests with a False Discovery Rate (FDR) algorithm. Limb bud pellet cultures were prepared from mesenchymal cells isolated from the forelimbs of 11.5 dpc BALB/c and DBA/1 embryos. High-density pellets were cultured in DMEM-F12 or GDF5 for 7 days. RNA was extracted and chondrogenic and osteogenic markers were assessed by qPCR. <h3>Results</h3> Incidence of ankylosing enthesitis was lower in the F2 generation as compared to wild-type DBA/1 males (42% vs. 72%; p&lt;0.0001). When applying the FDR algorithm for 159 markers, associations with <i>D3MIT199</i> and <i>D3MIT160</i> were significant (p&lt;0.016). Adjacent markers were additionally genotyped. In the associated region between markers <i>D3MIT42</i> and <i>D3MIT129</i>, 162 genes were found among which <i>Bmpr1b, Cxxc4, Lef1, Papss1, Pitx2</i>, and <i>Ube2d3</i>. Only BMP receptor type 1b (<i>Bmpr1b</i>) was specifically upregulated in mice with spontaneous arthritis as demonstrated by qPCR. Additionally, Bmpr1b ligand, GDF5, induces differential expression of osteogenic genes in cultures from BALB/c mice as compared to DBA/1 mice. Osterix (OSX), osteocalcin (OC) and bone siaoloprotein (BSP) are all significantly upregulated in BALB/c cultures after 5 days in the presence of GDF5. <h3>Conclusions</h3> Using F2 mouse genetics in the analysis of joint ankylosis, we identified a locus on chromosome 3 that shows association to disease. Within this locus several genes may play a role in ankylosis, however, our functional data suggests that <i>Bmpr1b</i> is involved, most likely as a modifier gene. The response to GDF5 in limb bud cultures highlights that differences exist in the GDF5-Bmpr1b pathway in BALB/c and DBA/1 mice, further corroborating an essential role for BMPs in human and murine ankylosis. <h3>Disclosure of Interest</h3> None Declared
Cerebriform Nevus Sebaceous
Authors: Jeong Deuk Lee, Hei Sung Kim
Journal: New England Journal of Medicine (2015)

A 12-year-old girl presented with a tan plaque on her scalp that had gradually increased in size since birth, with a cerebriform appearance. Histologic findings showed papillomatous epidermal hyperplasia and large numbers of mature sebaceous glands with no evidence of cancer.
Abstract P6-15-04: Targeting the PI3K Pathway Enhances the Effect of PARP-1 Inhibition in BRCA1 Deficient Breast Cancer Cells
Authors: S Kimbung, K Aaltonen, S Gruvberger-Saal, P Berglund, I. Hedenfalk
Journal: Cancer Research (2010)

Abstract Background: Available targeted therapies have improved the prognosis for many women diagnosed with breast cancer. However, more than 15% of cases do not benefit from these targeted agents. Amongst these are tumours with Breast cancer 1 (BRCA1) dysfunction, triple-negative and basal-like breast cancers, which remain a treatment challenge and are associated with a poor outcome. New approaches to specifically target these groups of breast tumors are needed. The DNA damage repair defects associated with lack of BRCA1 confers sensitivity to poly-(ADP-ribose) polymerase 1 (PARP-1) inhibitors. Furthermore, most BRCA1 mutated tumours do not express the phosphatase and tensin homolog (PTEN) implying activation of the phosphatidylinositol-3 kinase (PI3K) pathway which promotes cell survival and resistance to apoptosis. The aim of this study was to investigate if co-targeting the PI3K pathway can improve the response of BRCA1 mutated cells to PARP-1 inhibition. Material and methods:, Two BRCA1 and PTEN deficient breast cancer cell lines; MDA-MB-436 and SUM149, were treated with the PARP-1 inhibitor AG14361 (1-(4-dimethylaminomethyl-phenyl)-8-9-dihydro-7H-2,7,9a-benzo[cd]azulen-6-one) and the PI3K inhibitor LY294002 (2-(4-morpholinyl)-8-phenyl-chromone), as single agents and in combination. Cytotoxicity was estimated using the sulpho-rhodamine B assay while cell cycle phase distribution and DNA integrity were analyzed by flow cytometry. Results: AG14361 induced DNA damage leading to G2/M arrest and decreased viability. LY294002, on the other hand, affected the cell cycle by arresting cells in G1. Importantly, combining AG14361 with LY294002 further decreased survival (P&amp;lt;0.001) with a concomitant decrease in G2/M (P&amp;lt;0.05). Discussion: This observation may indicate a combination specific up-regulation of apoptosis and suggests that LY294002 potentiates the effects of AG14361. Our results may represent an improved selective targeted treatment strategy for BRCA1 deficient breast cancers and other cancers with DNA damage repair defects and activated PI3K signalling. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-15-04.