tbuckley/cabot-search huggingface dataset:
Peripheral Blood Lymphocyte/Monocyte Ratio At Diagnosis Is Independent of the Cell of Origin in Predicting Survival in Diffuse Large B-Cell Lymphoma,
Authors: Luis F. Porrata, Kay M. Ristow, Joseph P. Colgan, Thomas M. Habermann, Thomas E. Witzig, David James Inwards, Stephen M. Ansell, Ivana N. Micallef, Patrick B. Johnston, Grzegorz S. Nowakowski, Carrie A. Thompson, Svetomir N. Markovic
Journal: Blood (2011)
Exploratory study of histopathological characteristics of Hepatocellular carcinoma (HCC) in African (Tanzania) and Caucasian (Italian) population
Authors: M. Nestory, A. Casadei Gardini, S. Bravaccini, P. Serra, K. Jackson, P. Akwilina, S.H. Austin, G.L. Frassineti, D. Amadori
Journal: Annals of Oncology (2015)
Abstract 1462: Non-inflammatory role of ASC-dependent inflammasomes in promoting gastric tumourigenesis via IL-18
Authors: Brendan Jenkins, Virginie Deswaerte, Alison West, Paul Nguyen, Tracy Putoczki
Journal: Cancer Research (2016)

Abstract Introduction Gastric cancer is the third most lethal cancer worldwide and represents a growing number of cancers linked with inflammation. However, the identity of innate immune regulators with oncogenic potential in the host gastric mucosal epithelium remains obscure. We aim to identify the molecular basis by which specific pattern recognition receptors belonging to the inflammasome family promotes gastric tumorigenesis. Experimental procedures We have employed the gp130F/F gastric cancer mouse model coupled with mice lacking specific inflammasome-related genes. In addition, human gastric cancer tumor (and matched non-tumor) biopsies and cell lines were used. Immunohistochemistry on gastric tissue sections was used to assess the extent of cellular proliferation, apoptosis, inflammation and angiogenesis, and quantitative real-time PCR was used to measure the expression of genes of interest. Immunoblotting and ELISA were used to measure the activation and expression levels of inflammasome-related proteins. Results A causal role for ASC-dependent inflammasomes in gastric tumorigenesis was confirmed upon the genetic ablation of ASC in gp130F/F:Asc-/- mice, which resulted in a ∼50% reduction in tumor burden compared to parental gp130F/F mice. The suppressed gastric tumorigenesis in gp130F/F:Asc-/- mice was associated with increased gastric epithelial (tumor) cell apoptosis, as determined by elevated numbers of TUNEL and caspase-8 positive cells. Surprisingly however, no changes in the number and activation status of inflammatory cells were observed. The suppressed gastric tumorigenesis in gp130F/F:Asc-/- mice was also characterized by a gene signature comprising apoptotic-related genes. In gastric tumor tissue, IL-18, but not IL-1β, protein levels were augmented compared to matched non-tumour tissue, and genetic ablation of IL-18 in gp130F/F:IL-18-/- mice suppressed gastric tumorigenesis comparable to that observed upon ASC deficiency. The treatment of human gastric cancer cells with IL-18 also potentiated their growth compared to IL-1β. Conclusions Collectively, these data reveal that ASC-dependent inflammasomes and their downstream mediator IL-18 represent a novel oncogenic mechanism in gastric cancer. Citation Format: Brendan Jenkins, Virginie Deswaerte, Alison West, Paul Nguyen, Tracy Putoczki. Non-inflammatory role of ASC-dependent inflammasomes in promoting gastric tumourigenesis via IL-18. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1462.
Differential gene expression in liposarcoma: Insight into pathways for dedifferentiation?
Authors: Dale Han, Gregory C Bloom, Marilyn M Bui, Steven Enkemann, Hideko Yamauchi, Gang Han, Anthony Paul Conley, Jonathan S. Zager, David Cheong, Damon R. Reed, Robert S Lavey, Vernon K. Sondak, Douglas D Letson, Ricardo Jorge Gonzalez
Journal: Journal of Clinical Oncology (2012)

10048 Background: Liposarcoma (LPS) dedifferentiation signifies conversion to a clinically aggressive phenotype, but the biologic processes required for this change have not been determined. We describe differential gene expression patterns between well-differentiated (WD) and dedifferentiated (DD) tumors to determine pathways involved in LPS dedifferentiation. Methods: From 1999 to 2006, 121 fatty tumors were resected at a single institution. Twenty tumors, consisting of atypical lipomatous tumors (ALT), WD LPS or DD LPS, were randomly selected and clinicopathologic characteristics were retrospectively reviewed. Gene expression profiling was performed on extracted RNA using the Affymetrix GeneChip platform. Differentially expressed genes were obtained and gene network analysis was done using GeneGO by MetaCore. Results: Median age was 59 years and 70% of cases were male. WD tumors, consisting of 3 ALT and 6 WD LPS, were compared with 11 DD LPS. After a median follow-up of 64 months, 7 patients had died of whom 6 had DD LPS. DD histology was associated with lower overall survival (p&lt;0.05). Significance Analysis of Microarrays for WD tumors vs. DD LPS using a 0% false discovery rate showed differential expression of 188 genes. Network analysis of genes from WD tumors vs. DD LPS showed significant (p&lt;0.001) differential regulation of glucose-activated transcription factor ChREBP (carbohydrate response element binding protein), a key element involved in lipogenesis, gluconeogenesis and glycolysis. There was also significant differential regulation of insulin signaling, PI3K-dependent and PKA signal transduction pathways and of amino acid, fatty acid and glucose metabolism pathways (p&lt;0.05). These pathways, based on Gene Ontology cellular processes, mapped to gene networks primarily involved in lipid metabolism (p&lt;0.05). Conclusions: Differential expression of genes involved in lipid metabolism networks is seen in DD LPS and changes in lipid metabolism may be associated with dedifferentiation. These differential gene expression patterns may help identify fatty tumors potentially at risk for progressing to a malignant or DD state and provide prognostic factors and therapeutic targets for patients with LPS.
Abstract 3551: Discovery of orally bioavailable novel Mcl-1 inhibitors that exhibit selective anti-proliferative activity in Mcl-1 sensitive cancer cell lines
Authors: Taekyu Lee, Zhiguo Bian, Johannes Belmar, Subrata Shaw, James C. Tarr, Bin Zhao, Nick Pelz, DeMarco Camper, Craig M. Goodwin, Allison L. Arnold, John L. Sensintaffar, Carrie F. Browning, Olivia W. Rossanese, Edward T. Olejniczak, Stephen W. Fesik
Journal: Cancer Research (2016)

Abstract Myeloid cell leukemia-1 (Mcl-1) is a member of the Bcl-2 family of proteins that regulate apoptosis. Amplification of Mcl-1 is found in various cancers, which causes the evasion of apoptosis and is one of the major resistance mechanisms for many chemotherapies. Mcl-1 mediates its effects primarily through high affinity interactions with pro-apoptotic BH3 containing proteins, Bak and Bax. Thus targeting Mcl-1 with small molecule inhibitors is a promising strategy but a very challenging task. Using fragment-based methods and structure-based design, we discovered a novel class of potent Mcl-1 inhibitors that exhibit selective anti-proliferative activity. New leads containing a tricyclic indole lactam scaffold exhibited dissociation constants of &amp;lt;0.5 nM with &amp;gt;1000-fold selectivity for Mcl-1 over Bcl-xL and Bcl-2. They also promoted apoptosis only in Mcl-1 sensitive cancer cell lines by activating caspases in a dose-dependent manner. These results provide a strong proof of concept for a selective inhibition of Mcl-1 function as an effective anti-cancer therapy. Finally, our leads also possess desirable pharmaceutical properties including in vivo oral bioavailability and represent an ideal starting point for developing clinically useful Mcl-1 inhibitors for the treatment of a wide variety of cancers. Citation Format: Taekyu Lee, Zhiguo Bian, Johannes Belmar, Subrata Shaw, James C. Tarr, Bin Zhao, Nick Pelz, DeMarco Camper, Craig M. Goodwin, Allison L. Arnold, John L. Sensintaffar, Carrie F. Browning, Olivia W. Rossanese, Edward T. Olejniczak, Stephen W. Fesik. Discovery of orally bioavailable novel Mcl-1 inhibitors that exhibit selective anti-proliferative activity in Mcl-1 sensitive cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3551.
CD4+ T-Cell STAT3 Activity Is Increased before Acute Graft-Versus-Host Disease Onset and Its Pharmacologic Inhibition Selectively Controls Alloresponses
Authors: Brian C Betts, Anandharaman Veerapathran, Francisca Beato, Harshani R Lawrence, Said M Sebti, Joseph A Pidala, Claudio Anasetti
Journal: Blood (2014)
Abstract 4379: Exosomes isolated from ovarian cancer cells transfer oncogenic features to the target cells promoting epithelial to mesenchymal transition
Authors: Miharu Kobayashi, Laura Cohelo, Dominic Guanzon, Katherin Scholz-Romero, Melissa Brown, Richard Kline, Li Li, Gregory Rice, Carlos Salomon
Journal: Cancer Research (2016)

Abstract Introduction: Recent studies establish the role of exosomes in cell-cell communication in cancer. As adaptation to hypoxia is a critical step in tumor progression, the aim of this study was to test the hypotheses that hypoxia promotes epithelial to mesenchymal transition (EMT) and that exosomes isolated from hypoxic cancer cells transfer oncogenic properties to target cells. Methods: CaOV-3 cell line was used as model of ovarian cancer. Cells were cultured under 8% O2 (normoxia) and 1% O2 (hypoxia) for 48 hours. Exosomes were isolated from cell-conditioned media by differential and buoyant density centrifugation. Exosomes were characterised by the presence of TSG101 using Western Blot, size distribution (Nanosight™) and morphology by electron microscopy. Exosomal protein and miRNA content were determined using liquid chromatography mass spectrometry (5600 Triple TOF, AB Sciex,) and an Illumina NextSeq 500 Platform, respectively. The effects of exosomes released from CaOV-3 incubated under 1% O2 on EMT induction in CaOV-3 cells cultured under 8% O2 were assessed by the measuring the ratio of E-cadherin (epithelial marker) to N-cadherin (mesenchymal marker) by Wester Blot and the expression of 84 key genes involve in the EMT (RT2 Profiler™ PCR Array, QIAGEN). Results: Exosomes were identified as spherical vesicles with a typical cup-shape, diameters ranging from 50 to 100 nm with the expression of TSG101. Exosome release from ovarian cancer cells was ∼4-fold higher under hypoxic than normoxic conditions (p &amp;lt;0.001). Hypoxia-specific exosomal proteins and miRNAs were identified. Hypoxia induced EMT (increased N-cadherin/E-cadherin ratio) on CaOV-3 cells compared to cells cultured under 8% O2. Interestingly, exosomes isolated from hypoxic conditions mimic the effect of hypoxia on cells cultured under 8% O2, involving the unregulated of a set of transcription factors associated with EMT such as SNAIL1/SNAIL2, bHLH (E47, E2-2, and TWIST1/TWIST2), and ZEB1/ZEB2. Conclusion: The data obtained is consistent with the hypothesis that exosomes released from cancer cells modify the phenotype of target cells by transferring pro-oncogenic molecules inducing cancerous phenotype of receipt cells, contributing to tumour growth and metastasis. Citation Format: Miharu Kobayashi, Laura Cohelo, Dominic Guanzon, Katherin Scholz-Romero, Melissa Brown, Richard Kline, Li Li, Gregory Rice, Carlos Salomon. Exosomes isolated from ovarian cancer cells transfer oncogenic features to the target cells promoting epithelial to mesenchymal transition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4379.
EGFR regulates macrophage activation and function in bacterial infection
Authors: Dana M. Hardbower, Kshipra Singh, Mohammad Asim, Thomas G. Verriere, Danyvid Olivares-Villagómez, Daniel P. Barry, Margaret M. Allaman, M. Kay Washington, Richard M. Peek, M. Blanca Piazuelo, Keith T. Wilson
Journal: Journal of Clinical Investigation (2016)

EGFR signaling regulates macrophage function, but its role in bacterial infection has not been investigated. Here, we assessed the role of macrophage EGFR signaling during infection with Helicobacter pylori, a bacterial pathogen that causes persistent inflammation and gastric cancer. EGFR was phosphorylated in murine and human macrophages during H. pylori infection. In human gastric tissues, elevated levels of phosphorylated EGFR were observed throughout the histologic cascade from gastritis to carcinoma. Deleting Egfr in myeloid cells attenuated gastritis and increased H. pylori burden in infected mice. EGFR deficiency also led to a global defect in macrophage activation that was associated with decreased cytokine, chemokine, and NO production. We observed similar alterations in macrophage activation and disease phenotype in the Citrobacter rodentium model of murine infectious colitis. Mechanistically, EGFR signaling activated NF-κB and MAPK1/3 pathways to induce cytokine production and macrophage activation. Although deletion of Egfr had no effect on DC function, EGFR-deficient macrophages displayed impaired Th1 and Th17 adaptive immune responses to H. pylori, which contributed to decreased chronic inflammation in infected mice. Together, these results indicate that EGFR signaling is central to macrophage function in response to enteric bacterial pathogens and is a potential therapeutic target for infection-induced inflammation and associated carcinogenesis.
Cell-Derived Microparticles (C-MP) Are Elevated in Splenectomized Patients and Depressed in Those with Hypersplenism, Suggesting Spleen as Scavenger of C-MP.
Authors: Vincenzo Fontana, Wenche Jy, Pamela Dudkiewicz, Lawrence L. Horstman, Carlos Bidot, Yeon-Soong Ahn
Journal: Blood (2006)
Pulmonary neuroendocrine carcinomas: A population-based survey
Authors: D. Morgensztern, J. Subramanian, R. Govindan
Journal: Journal of Clinical Oncology (2008)

17522 Background: Pulmonary neuroendocrine tumors are currently subdivided into four major subgroups named typical carcinoid (TC), atypical carcinoid (AC), small cell lung cancer (SCLC), and large cell neuroendocrine carcinoma (LNEC). Despite similarities in pathological features and a possible common cell of origin, the clinical outcomes are markedly different with a spectrum of aggressiveness from low-grade TC to high grade SCLC. Available studies however, are limited by the small number of patients. We conducted a population survey to further define the demographics and outcomes for these patients. Methods: The Surveillance Epidemiology End Results (SEER) database was searched for patients with TC, AC, SCLC, and LNEC diagnosed between 2000 and 2003. Only patients with known stage and survival data were included in the analysis. To allow a better definition of tumor behavior in each subset of patients, the cancer-specific survival was calculated for all stages, stage I treated by surgery, and stage IV. Results: There were 19,531 patients eligible including 1,230 TC, 75 AC, 17,821 SCLC, and 405 LNEC. Median age was 58, 61, 67, and 66 years respectively. The highest proportion of patients aged ≤ 40 was seen in TC and AC (17% and 12% respectively), and the lowest in LNEC and SCLC (2.2 and 0.7%). TC and AC were more common in women (62% and 61%) whereas LNEC and SCLC were more common in men (55% and 52%). Stage I was seen most commonly in TC and AC (77% and 52% respectively), whereas stage IV was more common in SCLC (58%). Three-year cancer-specific survival for all stages, stage I treated by surgery, and stage IV are described in the table below. Conclusions: TC and AC are more common in women, had the highest proportion of younger patients, usually presented with earlier stages, and had better outcomes. LNEC is associated with better cancer-specific survival compared with SCLC. Table TC AC SCLC LNEC Overall survival 94% 76% 8.5% 27% 3-year survival for resected stage I 98% 95% 55% 65% 3-year survival for stage IV 62% 23% 2.5% 6.4% No significant financial relationships to disclose.
Abstract 1909: miR-30c blocks tumor cell homotypic aggregation and promotes anoikis to prevent breast cancer metastasis
Authors: Xia Liu, Beijie Yu, Wenjing Chen, Huiping Liu
Journal: Cancer Research (2016)

Abstract Circulating tumor cells (CTCs) are considered the seeds of distant metastasis, and may be a predictor of poor prognosis in patients with metastatic breast cancers. Compared to single CTCs, clusters of multiple CTCs possess higher metastatic capacity in mouse breast cancer models, indicating that aggregation increases the survival of CTCs in the circulation. However, the molecular mechanisms by which clustered CTCs mediate tumor cell survival are unclear. In this study, we found that miR-30c, which has been identified as an anti-metastatic microRNAs, inhibited primary breast cancer cell homotypic aggregation in vitro by real-time monitoring. Interestingly, only aggregated but not single tumor cells can survive during culture. The death of dissociated primary tumor cells in vitro is caused by anoikis, a form of programmed cell death which is induced by detachment of anchorage-dependent cells from the surrounding extracellular matrix. Therefore, the role of miR-30c in anoikis was determined by culturing breast cancer cells in poly-hema coated plates. We found that miR-30c promoted anoikis, evaluated by Annexin-V staining and caspase3/7 activity. Mechanistic studies indicated that inhibition of Vimentin (Vim), a positive regulator of epithelial-to-mesenchymal transition (EMT), was required for miR-30c induced anoikis. In vivo, lung metastasis was inhibited by miR-30c after tail vein injection of miR-30c over-expressed cells. In summary, our findings provide the new insights into the mechanisms of miR-30c-mediated metastasis inhibition and suggest that targeting CTC clusters could be a novel strategy to prevent metastasis. Citation Format: Xia Liu, Beijie Yu, Wenjing Chen, Huiping Liu. miR-30c blocks tumor cell homotypic aggregation and promotes anoikis to prevent breast cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1909.
Abstract 3671: Polarity and tumor development: Regulation by adenomatous polyposis coli
Authors: Alyssa C. Lesko, Madeline Chandra, Jenifer R. Prosperi
Journal: Cancer Research (2016)

Abstract The process of epithelial polarity is tightly regulated by multiple complexes including aPKC, PAR, and Crumbs proteins. Our laboratory has recently investigated loss of Adenomatous Polyposis Coli (APC) in the MDCK 3D culture system. We have observed a lack of hollow lumens and mislocalization of podocalyxin (gp135) to the basal surface, both of which are independent of the canonical Wnt/β-catenin signaling pathway. We further showed that the c-terminus of APC, which contains binding domains for polarity proteins (Dlg and Scrib) and cytoskeletal proteins (microtubules and actin), is responsible for the observed phenotypes. In the current study, we have investigated the molecular mechanisms required for the inversion of polarity and the potential impact on tumorigenesis. We have made the novel observation that different mechanisms are responsible for the increased size versus altered polarity observed in cysts derived from APC-KD cells. Alterations in size, although independent of changes in proliferation and/or apoptosis, are regulated by the c-terminal domain, focal adhesion kinase (FAK), Src, and β1-integrin. Despite this, the mis-localization of gp135 is only rescued by the c-terminal domain of APC, suggesting a unique molecular mechanism. As loss of epithelial polarity is an early marker for tumor development, we investigated tumor-associated phenotypes. APC-KD cells were found to grow larger colonies in soft agar, and have increased migration in wound-filling assays, which appeared to be regulated through similar molecular mechanisms. These data suggest that APC regulates polarity and associated disease phenotypes (including kidney development, cardiovascular disease, and cancer) through pathways independent of Wnt signaling. Citation Format: Alyssa C. Lesko, Madeline Chandra, Jenifer R. Prosperi. Polarity and tumor development: Regulation by adenomatous polyposis coli. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3671.
Excessively closed science hurts
Authors: Fred H. Geisler
Journal: BMJ (2008)

I would like to add to Lenzer and Brownlee’s reporting of my comments on how excessively closed science can hurt physicians and patients.1

Statistician Michael Bracken led the NASCIS 2 and 3 studies of high dose steroids in acute spinal cord injury.2 The National Institute of Neurological Disorders and Stroke conducted a public campaign in advance of the scientific publication of NASCIS …
Now you see it, now you don’t
Authors: Lauren Berg, Anietie Ekong, Susan Rowe, Dimitris A Tsitsikas
Journal: BMJ (2016)

A 40 year old black British man with known sickle cell anaemia presented to the emergency department with a nine hour history of left-sided pleuritic chest pain. The patient also had pain in both arms and legs. Three weeks earlier, he had had a productive cough treated with oral antibiotics in the community. A chest radiograph at that time showed no consolidation, and his symptoms had since resolved.

On admission, he reported excruciating pain, his oxygen saturations were 81% on air, and his respiratory rate was 30 breaths/min. Clinical examination was unremarkable except for reduced air entry throughout the lung fields, and he was apyrexial. His haemoglobin level was 60 g/L (baseline 69 g/L) and white cell count was 23 × 109/L with neutrophilia. His ECG showed no ischaemic changes. His admission chest radiograph can be seen in figure 1⇓ (left).



Fig 1  Patient’s chest radiographs: at presentation (left), and 36 hours later (right)



He was treated with high flow oxygen, intravenous fluids and both simple and opioid analgesia. Four hours later he was more settled, his respiratory rate had decreased, and widespread crepitations—worse on the right—had developed. The patient was admitted to the haematology ward and received automated red cell exchange transfusion, oxygen therapy, intravenous fluids, analgesia, incentive spirometry, and antibiotics.

Figure 1⇑ (right) shows his second chest radiograph, performed 36 hours later.

1.  What are the diagnosis and differential diagnoses?

2.  What improvements does the second radiograph show, and why have they occurred?

3.  What is the long term management of a patient such as this in the community and in the specialist haematology setting?

### 1. What are the diagnosis and differential diagnoses?

#### Short answer

The diagnosis is acute chest syndrome. Differential diagnoses include pulmonary embolism and vaso-occlusive crisis of the ribs.

#### Discussion

Acute chest syndrome (ACS) is an acute illness characterised by fever or respiratory symptoms, or both, accompanied by a …