tbuckley/cabot-search huggingface dataset:
Abstract P6-05-11: Leptin and Leptin receptor expression in human breast cancer
Authors: U Wazir, Sarakbi W Al, WG Jiang, K Mokbel
Journal: Cancer Research (2012)

Abstract INTRODUCTION: Leptin is a protein that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones and has been suggested to act as a growth factor in neoplasms. Obesity has been linked to increased risk of breast cancer in postmenopausal women. Increased peripheral production of oestrogen has been regarded as the main cause for this association, but other factors affecting fat metabolism may be implicated. There is recent evidence that Leptin stimulates cancer cell proliferation in MCF-7 cancer cells. Both Cox2 and hTERT have been proposed as mediators of Leptin's carcinogenic role. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of Leptin and Leptin receptor were consistent with a tumour proliferative function and whether levels from these genes were positively correlated with clinical outcome in breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of Leptin and its receptor were determined using quantitative PCR and normalised against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analysed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of Leptin and Leptin receptor mRNA were significantly higher in malignant samples (p = 0.0011 and 0.0014 respectively). This difference remained statistically significant when comparing levels between normal samples and all malignant subgroups according to their NPI, grade, stage, local recurrence, and distant metastasis in both ER receptor positive and negative samples. It was also present across all histological types for both Leptin and its receptor. There was no significant change in mRNA transcription levels correlating with tumour grade, stage, disease free survival, or development of loco regional recurrence. There was also no statistically significant difference in levels of expression of both Leptin and its receptor when comparing ER positive to negative patients (p = 0.74 and 0.27 respectively). Leptin levels showed a significantly positive correlation with Leptin receptors (r = 0.504, 0.0000000222). We have observed no significant correlations between Leptin and hTERT or Cox2. CONCLUSION: This study demonstrates compelling evidence that both Leptin and Leptin receptor mRNA transcription levels are more readily expressed in cancerous tissues providing further evidence that it plays a significant role in the process of breast carcinogenesis. However, Leptin levels did nor correlate with tumor's stage, clinical outcome, hTERT or Cox-2 levels. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-11.
A Double Blind Randomised Clinical Trial to Prevent Serious Side Effects of Dexamethasone during Pediatric Acute Lymphoblastic Leukemia Treatment
Authors: Lidewij T Warris, Marry M van den Heuvel-Eibrink, Femke K Aarsen, Saskia MF Pluijm, Marc B Bierings, Cor van den Bos, Christian M. Zwaan, Wim JE Tissing, Margreet A Veening, Rob Pieters, Erica LT van den Akker
Journal: Blood (2015)
Antipsychotic Treatment of Young Chinese Individuals From 2004 to 2015: A Population-Based Study in Hong Kong
Authors: Edwin Ho Ming Lee, Christy Lai Ming Hui, Jingxia Lin, Wing Chung Chang, Sherry Kit Wa Chan, Eric Yu Hai Chen
Journal: American Journal of Psychiatry (2016)

EDITOR: The increasing use of antipsychotic medications in young people has raised concerns in the United States regarding safety and indication (1).Such data on antipsychotic medication use in young people are lacking in Asian countries, as are data on the proportions prescribed by psychiatrists, considering prescription practices also differ from Western countries (2).We studied population-based antipsychotic prescribing trends in young people in Hong Kong.Antipsychotic medication data (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015) were retrieved from the database of the Hong Kong Hospital Authority of all public hospitals and institutions, covering more than seven million people (3).One or more filled antipsychotic prescriptions in a year qualified as antipsychotic use.A retrospective descriptive analysis of antipsychotics prescribed by psychiatrists to young patients (0-24 years) was performed (Table 1).Proportions of young people who were prescribed antipsychotics during each study year were calculated by age group (5-9, 10-14, 15-19, and 20-24 years), except the 0-4 age group, which had only a few prescriptions each year (range51-6).Population denominators were estimated using 2004-2015 data from the Hong Kong Census and Statistics Department (4).Our results showed that antipsychotic use in children increased from 2004 (ages 0-4, 0%; ages 5-9, 0.03%; ages 10-14, 0.09%) to 2015 (ages 0-4, 0%; ages 5-9, 0.11%; ages 10-14, 0.31%), and in adolescents and young adults from 2004 (ages 15-19, 0.25%; ages 20-24, 0.65%) to 2015 (ages 15-19, 0.47%; ages 20-24, 0.85%) (Figure 1).The percentage of antipsychotics prescribed by psychiatrists to young patients increased from 2004 (ages 5-9, 71.7%; ages 10-14, 77.7%; ages 15-19, 84.6%) to 2015 (ages 5-9, 92.5%; ages 10-14, 92.3%; ages 15-19, 88.1%).However, the percentage of prescribed antipsychotics declined in the 20-24 age group from 2004 (89.1%) to 2015 (86.9%).In summary, we found that the percentage of young people in Hong Kong treated with antipsychotics increased from 2004 to 2015; in the United States, the figure dropped for younger children from 2006 (0.14%) to 2010 (0.11%), and for older children from
New sociology for better understanding severe eosinophilic asthma: introducing the SOCS family
Authors: Delphine Gras, Pascal Chanez
Journal: European Respiratory Journal (2016)

Severe asthma is a heterogeneous condition characterised by a persistent uncontrolled situation with an inadequate response to current therapy [1]. This definition points the serious unmet needs of the patients and an urgent research effort to understand better the mechanisms sustaining this clinical condition for our community. However, severe asthma is still not identified as a distinct entity and is very heterogeneous. At present, several endotypes have been described based on the presence of upregulated cytokines leading to the recruitment, activation and increased survival of inflammatory cells such as eosinophils. One major endotype is related to T2 lymphocyte (T-helper cell type 2 and innate lymphoid cell type 2) activation, which is observed in most severe asthma patients. Fortunately, several new drugs are or have been developed to interfere with this endotype, but there are still important gaps of knowledge to be filled and clearly, other targets should be identified to develop innovative treatments [2]. SOCS proteins' involvement in severe eosinophilic asthma <http://ow.ly/lG943023yxZ>
Efficacy of Standard Dose R-CHOP Alternating with R-HiDAC Followed By ASCT As Initial Therapy of Mantle Cell Lymphoma: Cleveland Clinic Experience
Authors: Danyu Sun, Brian T. Hill, Lisa Rybicki, Basel Rouphail, Robert M Dean, Deepa Jagadeesh, Aaron T. Gerds, Betty K. Hamilton, Ronald M. Sobecks, Hien K. Duong, Steven Andresen, Navneet S. Majhail, Brad Pohlman, Matt E. Kalaycio, Brian J. Bolwell, Mitchell R. Smith
Journal: Blood (2014)
Rare mutations of the PIK3CA gene in a number of cancer types and discovery of a PIK3CA pseudogene
Authors: Claudia I. Muller, Carl W. Miller, Wolf K. Hofmann, Mitchell E. Gross, Christine S. Walsh, Norihiko Kawamata, H. Phillip Koeffler
Journal: Cancer Research (2005)

1016  Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that is a known regulator of cellular growth and proliferation. The PI3K pathway plays a critical role in the development of cancer. Somatic mutations in the p110-alpha catalytic subunit, PIK3CA, have been reported for colon (19-32%), gastric (25%), breast (8%-40%), lung (4%) and ovarian (6%) cancers as well as glioblastomas (5-27%), oligodendrogliomas (14%), medulloblastomas (5%) and astrocytomas (3%). Mutations cluster in two “hot spots” located in the helical (exon 9) and kinase (exon 20) domains. We performed mutational screening analysis of PIK3CA in several so far uninvestigated cancers: hematologic malignancies, lymphomas as well as endometrial, prostate and ovarian cancers. Cell lines and patient samples were examined by polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) and nucleotide sequencing of the two “hot spots”. Two colon adenocarcinoma cell lines (SKCol1, SW403) were used as positive controls and revealed the known missense mutation (Q546K) in exon 9. Twenty-eight endometrial cancer samples and 6 endometrial cancer cell lines (HEC59, HEC1B, RL95-2, KLE, AN3 and Ishikawa) were screened for mutations. One patient sample showed a mutation at codon 1025 in the kinase domain (exon 20) causing an amino acid change from Threonine to Alanine (T1025A). Ishikawa revealed a previously undocumented polymorphism for Threonine residue 1025 (T1025T). The same change was found in one of 43 primary lymphoma samples and in two MDS patients out of 46 AML and MDS samples. Twelve prostate cancer samples and two prostate cancer cell lines (LNCaP, DU145) together with 18 ovarian cancer samples and one ovarian cancer cell line (SKOV3) showed no shifted bands by SSCP-analysis. Sequencing a shift for the erythroid chronic myeloid leukemia cell line K562, revealed an amino acid change from Glutamic acid to Alanine at amino acid position 545 of exon 9 (E545A). Further analysis lead to the discovery of a previously unidentified PIK3CS pseudogene spanning exons 9 through 13 on chromosome 22. In summary, PIK3CA mutations occur infrequently in hematologic malignancies as well as prostate, ovary and endometrial tumors. Being aware of the PIK3CA pseudogene could prevent misleading mutational analysis of the PIK3CA gene.
The anti-inflammatory role of propranolol in cirrhosis: Preventing the inflammatory exhaustion?
Authors: Anderson Brito-Azevedo, Renata de Mello Perez, Henrique Sérgio Moraes Coelho, Eduardo de Souza Martins Fernandes, Raquel Carvalho Castiglione, Cristiane Alves Villela-Nogueira, Eliete Bouskela
Journal: Journal of Hepatology (2016)
Randomized phase II study of everolimus (E) versus everolimus plus bevacizumab (E+B) in patients (Pts) with locally advanced or metastatic pancreatic neuroendocrine tumors (pNET), CALGB 80701 (Alliance).
Authors: Matthew H. Kulke, Donna Niedzwiecki, Nathan R. Foster, Briant Fruth, Pamela L. Kunz, Hagen F. Kennecke, Edward M. Wolin, Alan P. Venook
Journal: Journal of Clinical Oncology (2015)

4005 Background: Both VEGF pathway and mTOR inhibitors are active in pNET. Treatment with the mTOR inhibitor E improves progression free survival (PFS), but it is not known if the addition of a VEGF pathway inhibitor to an mTOR inhibitor enhances antitumor activity in pNET. This randomized phase II study evaluated E or E+B in pts with advanced pNET. Methods: Pts were randomized 1:1 to receive either E (10 mg po qd) or E (10 mg po qd) co-administered with B (10 mg/kg IV q 2 wks). Pts in both arms received concurrent standard dose octreotide. The primary endpoint was PFS. The potential superiority of E+B vs. E was assessed using a stratified log-rank test with 90% power (1-sided α = 0.15) to detect a HR of 0.64. Secondary endpoints included overall survival (OS), response rate (RR), and safety. Results: 150 pts were randomized; 75 per arm. Pt characteristics were similar between treatment arms and included: median age 59 years (range 21-86), 56% male, ECOG PS 0 (57%) and 1 (43%), prior cytotoxic chemotherapy 24%. The median number of 28-day treatment cycles was 13 (E+B) and 12 (E), with a range of 1-44 cycles. Median follow up was 25.9 months. Pts on E+B experienced a higher frequency of grade 3 AEs, including diarrhea (14% vs. 3%; p = 0.01), hyponatremia (12% vs. 3%; p = 0.02), hypophosphatemia (11% vs. 3%; p = 0.04), proteinuria (16% vs. 1%; p = 0.001), and hypertension (41% vs. 12%; p < 0.0001). The frequency of grade 4 AEs was 11% in both arms; a single grade 5 event occurred on E. The median PFS was 16.7 mos (E+B) vs. 14 mos (E); HR = 0.80 (95% CI: 0.55, 1.17; 116 PFS events), 1-sided p = 0.12. The median OS was 36.7 mos (E+B) vs. 35.0 mos (E), HR = 0.75 (95% CI: 0.42-1.33; 49 OS events), 1-sided p = 0.16. Treatment with E+B was associated with a significantly higher RR (31%) compared to E alone (12%), p = 0.005) Conclusions: Treatment with E+B led to superior PFS compared to E but with more adverse events in this randomized phase II study. The RR was significantly higher in pts treated with E+B. The combination of E+B warrants further investigation in pts with advanced pNET. Clinical trial information: NCT01229943.
Complete remission of skin lesions in a patient with subcorneal pustular dermatosis (Sneddon-Wilkinson disease) treated with antimyeloma therapy: association with disappearance of M-protein
Authors: P.A. von dem Borne, M.F. Jonkman, R. van Doorn
Journal: British Journal of Dermatology (2016)

Subcorneal pustular dermatosis (SPD), or Sneddon–Wilkinson disease, is a rare pustular skin disease that follows a chronic relapsing course. A well‐known association exists between SPD and IgA monoclonal gammopathy of undetermined significance (MGUS), which exists in up to 40% of cases. SPD has also been observed in patients with IgA myeloma. In SPD, direct and indirect immunofluorescence studies do not reveal in vivo bound IgA to the epithelial cell surface, in contrast to IgA pemphigus, which has similar clinicopathological features. Here we describe the case of a male patient with SPD and a concurrent IgA MGUS who had been treated with dapsone for 20 years with frequent relapses. Following development of multiple myeloma, the patient was treated with intensive antimyeloma treatment consisting of high‐dose melphalan with autologous stem cell transplantation. This resulted in a complete remission of the myeloma with disappearance of the M‐protein. In addition, a sustained remission of SPD was achieved without further treatment. Twenty‐eight months after melphalan therapy the M‐protein reappeared in the serum, and 2 months later SPD reappeared with histopathologically proven skin lesions at predilection sites. Presence and absence of skin lesions was found to correlate with the presence and absence of the M‐protein in the serum. This is the first report of antimyeloma therapy inducing a long‐lasting remission in SPD. The findings in this patient strongly suggest a causal role for circulating IgA antibodies in the pathogenesis of SPD. Antimyeloma treatment should be considered in patients with IgA MGUS‐associated SPD refractory to other therapies.
The ADAM Trial
Authors: Surein Arulananda, Thomas John
Journal: JAMA Oncology (2016)

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International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency
Authors: H. Farkas, I. Martinez-Saguer, K. Bork, T. Bowen, T. Craig, M. Frank, A. E. Germenis, A. S. Grumach, A. Luczay, L. Varga, A. Zanichelli
Journal: Allergy (2016)

Background The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE. Methods During an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), pediatric data were presented and discussed and a consensus was developed by voting. Results The symptoms of C1-INH-HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1-INH-HAE, but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1-INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1-INH-HAE family member should be screened for C1-INH deficiency. Pediatric patients should always carry a C1-INH-HAE information card and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma-derived C1-INH, recombinant C1-INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow up patients in an HAE comprehensive care center. Conclusions The pediatric-focused international consensus for the diagnosis and management of C1-INH-HAE patients was created.
Novel algorithms for the pragmatic use of ultrasound in the management of patients with rheumatoid arthritis: from diagnosis to remission
Authors: Maria Antonietta D'Agostino, Lene Terslev, Richard Wakefield, Mikkel Østergaard, Peter Balint, Esperanza Naredo, Annamaria Iagnocco, Marina Backhaus, Walter Grassi, Paul Emery
Journal: Annals of the Rheumatic Diseases (2016)

The absence of specific guidance on how to use ultrasound (US) to diagnose and manage patients with inflammatory arthritis, especially with rheumatoid arthritis (RA) has hindered the optimal utilisation of US in clinical practice, potentially limiting its benefits for patient outcomes. In view of this, a group of musculoskeletal US experts formed a working group to consider how this unmet need could be satisfied and to produce guidance (additional to European League against Rheumatism (EULAR) imaging recommendations) to support clinicians in their daily clinical work. This paper describes this process and its outcome, namely five novel algorithms, which identify when US could be used. They are designed to aid diagnosis, to inform assessment of treatment response/disease monitoring and to evaluate stable disease state or remission in patients with suspected or established RA, by providing a pragmatic template for using US at certain time points of the RA management. A research agenda has also been defined for answering unmet clinical needs.
Platelets Impair NK Cell Immunosurveillance Of Metastasizing Tumor Cells By Altering Surface Expression and Shedding Of Ligands For The Activating Immunoreceptor NKG2D
Authors: Stefanie Raab, Korbinian Nepomuk Kropp, Alexander Steinle, Lothar Kanz, Hans-Georg Kopp, Helmut R. Salih
Journal: Blood (2013)
Molecular Differences between Screen-Detected and Interval Breast Cancers Are Largely Explained by PAM50 Subtypes
Authors: Jingmei Li, Emma Ivansson, Daniel Klevebring, Nicholas P. Tobin, Linda Sofie Lindström, Johanna Holm, Gabriela Prochazka, Camilla Cristando, Juni Palmgren, Sven Törnberg, Keith Humphreys, Johan Hartman, Jan Frisell, Mattias Rantalainen, Johan Lindberg, Per Hall, Jonas Bergh, Henrik Grönberg, Kamila Czene
Journal: Clinical Cancer Research (2016)

Purpose: Interval breast cancer is of clinical interest, as it exhibits an aggressive phenotype and evades detection by screening mammography. A comprehensive picture of somatic changes that drive tumors to become symptomatic in the screening interval can improve understanding of the biology underlying these aggressive tumors.Experimental Design: Initiated in April 2013, Clinical Sequencing of Cancer in Sweden (Clinseq) is a scientific and clinical platform for the genomic profiling of cancer. The breast cancer pilot study consisted of women diagnosed with breast cancer between 2001 and 2012 in the Stockholm/Gotland regions. A subset of 307 breast tumors was successfully sequenced, of which 113 were screen-detected and 60 were interval cancers. We applied targeted deep sequencing of cancer-related genes; low-pass, whole-genome sequencing; and RNA sequencing technology to characterize somatic differences in the genomic and transcriptomic architecture by interval cancer status. Mammographic density and PAM50 molecular subtypes were considered.Results: In the univariate analyses, TP53, PPP1R3A, and KMT2B were significantly more frequently mutated in interval cancers than in screen-detected cancers. Acquired somatic copy number aberrations with a frequency difference of at least 15% between the two groups included gains in 17q23-q25.3 and losses in 16q24.2. Gene expression analysis identified 447 significantly differentially expressed genes, of which 120 were replicated in an independent microarray dataset. After adjusting for PAM50, most differences were no longer significant.Conclusions: Molecular differences by interval cancer status were observed, but they were largely explained by PAM50 subtypes. This work offers new insights into the biological differences between the two tumor groups. Clin Cancer Res; 23(10); 2584-92. ©2016 AACR.