tbuckley/cabot-search huggingface dataset:
A4.18 The effects of SRC-family kinase inhibitors on osteoclast development<i>in vitro</i>
Authors: D Csete, D Győri, T Vántus, G Kéri, C Szántai-Kis, A Mócsai
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Osteoclasts are the unique bone-resorbing cells of hematopoietic origin; their development is regulated primarily by M-CSF, RANKL and integrin-mediated interactions. Our workgroup has previously tested thousands of Src-family kinase inhibitors produced by the Vichem Ltd on neutrophil granulocytes, which cells show many similarities with osteoclasts regarding signalling pathways. One of the most effective inhibitors was the PD166326, an anti-leukaemia drug candidate. Here we tested the effect of PD166326 on osteoclasts. <h3>Materials and methods</h3> Bone marrow cells were isolated from the long bones of C57Bl/6 mice on the 0. day and differentiated into osteoclasts <i>in vitro</i> in the presence of recombinant M-CSF and RANKL. Cultures were treated with PD166326 during different stages of osteoclastogenesis. Vehicle control samples received dimethyl sulfoxide (DMSO). Osteoclast differentiation was examined after 4 or 6 days by osteoclast-specific tartrate-resistant acid phosphatase (TRAP)-staining. Survival assay was performed at the 4th day using AnnexinV-PE and 7-AAD apoptosis and necrosis kit. Actin ring formation was observed with Lifeact EGFP transgenic mice. <h3>Results</h3> The number and the size of developing osteoclasts strongly decreased in case of the early administration of the inhibitor. The treatment of the cultures by 10 nM PD166326 practically blocked osteoclast development. When we administered the inhibitor later, from the 4th day – when the last main point of osteoclast development happens – only minor reduction was observed. The tendency to apoptosis did not increase in the PD166326 treated cultures. The administration of PD166326 did not influence the degradation of actin rings. <h3>Conclusions</h3> The anti-cancer drug PD166326 inhibited osteoclastogenesis in a very small concentration. We suppose that it has an effect on the early stage of osteoclast development. These data may be considered in the therapy of different cancers especially in metastatic bone diseases.
Can EUS Help Differentiate Macrocystic Serous Cystadenomas from Mucinous Cystadenomas of the Pancreas by Its Morphologic Characteristics?
Authors: SW Jung, SS Lee, SJ Bang, DH Kim, ID Jeong, DW Seo, SK Lee, MH Kim, JW Shin, NH Park
Journal: Endoscopy (2006)

Background/Aims: Benign pancreatic serous cystadenoma is usually distinguishable from mucinous cystadenoma (MCA), which requires resection because of its malignant potential. Macrocystic serous cystadenoma (M-SCA), a macrocystic variant of serous cystadenoma which is hard to distinguish from MCA, has recently been described. The aim of this study was to describe the morphologic characteristics of M-SCA with EUS, in order to differentiate M-SCA from MCA. Subjects and Methods: Clinical and morphologic characteristics on EUS were reviewed from 31 consecutive patients with M-SCA or MCA who had undergone surgery. Results: Resected specimens were available for 11 M-SCAs and 20 MCAs. Significant differences in characteristics were observed with age (44 years old, 26–58 for M-SCA vs. 57 years old, 31–68 for MCA, p=0.011) and location within the pancreas (64% in head for M-SCA vs. 85% in body or tail for MCA, p=0.013). No significant differences on EUS were observed between both groups regarding the type of loculation, cyst wall, and echo-pattern of cyst contents. But, many cases of M-SCA had microcysts (82%) when compared with 15% of MCA (p<0.001), and lobulated configuration of cyst was more frequently seen in M-SCA than MCA (91% vs. 25%, p=0.001). The combination of microcysts and lobulated configuration of cyst had sensitivity of 90%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 95% for the diagnosis of M-SCA when compared with MCA. Conclusions: M-SCA tends to occur at a relatively younger age than MCA and locate mainly in the head of the pancreas. While conventional imaging modalities display considerable morphologic overlap between M-SCA and MCA, EUS reveals characteristic findings including microcysts and lobulated configuration of cyst, which may help differentiate M-SCA from MCA.
Abstract 913: 5,10-Methylenetetrahydrofolate reductase C677T allele frequency and childhood leukemia incidence in predominantly European ancestry countries
Authors: Kimberly J. Johnson, Logan G. Spector
Journal: Cancer Research (2010)

Abstract 5,10-Methylentetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) have been intensely studied as cancer susceptibility alleles. For childhood leukemia, data have indicated that the most commonly studied MTHFR SNP, C677T, is associated with a slightly reduced risk of acute lymphoblastic leukemia (ALL). Both childhood leukemia incidence and MTHFR allele frequencies show variation worldwide. Our objective was to conduct an ecologic study to determine whether the MTHFR C677T allele frequency and childhood leukemia incidence are associated. We used cancer incidence data collected by the International Agency for Cancer Research from 22 registries that captured 19,025 leukemia cases diagnosed between the ages of 0 and 14 years from the United States, Canada, Australia, and 18 European countries; data were restricted to registries with majority European ancestry populations in order to minimize confounding by ancestry. MTHFR allele frequencies were gathered from the literature to match as closely as possible the registry populations. We modeled the association between childhood leukemia incidence and MTHFR C677T allele frequency using Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs). Estimates of the minor C677T allele frequency ranged from 24% in Finland to 44% in Italy. There was a weak inverse correlation between leukemia incidence and MTHFR C677T allele frequency (r=0.19), that was stronger for ALL (r=0.30). Acute nonlymphoblastic leukemia (ANLL) incidence was positively correlated with MTHFR C677T allele frequency (r=0.36). Poisson regression results from linear models showed that the incidence of childhood leukemia decreased by 5% (95% CI 3%-6%) for every 5% increase in the C677T allele frequency. A similar pattern was observed for ALL with a RR of 0.93 (95% CI=0.92-0.95) but not acute non-lymphoblastic leukemia (ANLL) (RR=1.04, 95% CI=1.00-1.07). The significant inverse associations between the C677T allele frequency and leukemia and ALL incidence were specific to incidence rates for children diagnosed &amp;lt;10 years. These results are consistent with the results of case-control studies of the association between childhood leukemia and MTHFR allele frequency suggesting a modest risk reduction in association with the C677T allele. The strengths and limitations of ecological vs. case control study designs will be discussed in the context of these results to provide insight into the causal relationship between the MTHFR minor allele frequency and childhood leukemia risk. This research was supported by NIH grant T32 CA099936. 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 913.
Abstract 496: Inflammatory responses with infiltrating DC and functional cytotoxic T lymphocytes in the dermal vaccination sites of GVAX/ipilimumab treated prostate cancer patients.
Authors: Saskia J. Santegoets, Leonieke JJ van Mens, Jeroen AM Beliën, Anita GM Stam, Sinead M. Lougheed, Rik J. Scheper, Shabnam Samiei, Helen Gall, Karin Jooss, Jean-Marie Cuillerot, Natalie Sacks, Kirsten Hege, Winald R. Gerritsen, Alfons JM van den Eertwegh, Tanja D. de Gruijl
Journal: Cancer Research (2013)

Abstract We have been studying the safety and clinical efficacy of the Prostate GVAX vaccine (consisting of two allogeneic GM-CSF secreting tumor cell lines: LNCaP and PC3) and the CTLA-4 blocking antibody ipilimumab in prostate cancer patients in a phase I/II dose escalation/expansion trial. To assess immune reactivity against the GVAX vaccine, immune infiltrate analysis of the vaccination sites was performed. Punch biopsies of the vaccination site were taken 48 hours after the 1st, 5th, and 11th injections and analyzed by immunohistochemical staining. Injection of the GVAX vaccine evoked striking local reactions that were characterized by local erythema, induration and swelling in all patients. Analysis of the vaccination site biopsies revealed that the GVAX/ipilimumab combination resulted in an inflammatory response in the skin with intradermal infiltrates of CD1a+ dendritic cells (DC), DC-SIGN+/CD68+ immature DC/macrophages, CD14+ monocyte-like cells, eosinophils, and of CD4+, CD8+, and Granzyme-B+ T lymphocytes. Strikingly, CD56+ NK cells were completely absent. The inflammatory response significantly increased over the course of treatment and resulted in accelerated clearance of the vaccine in vivo. Moreover, analysis revealed that the PC3 vaccine was more immunogenic, and induced a more potent anti-vaccine T cell response. The latter was confirmed in an in vitro cytotoxicity assay. Upon multiple vaccinations T cell reactivity to PC3 was significantly enhanced in the PC3 but not in the LNCaP vaccination sites, whereas reactivity to LNCaP was not enhanced in either vaccination site. We conclude that the GVAX/ipilimumab combination elicits a local immune infiltrate that increases over time, consistent with an induced CD8+ effector T cell mediated cytolytic response, only in vaccination sites of the PC3 component of the vaccine. Citation Format: Saskia J. Santegoets, Leonieke JJ van Mens, Jeroen AM Beliën, Anita GM Stam, Sinead M. Lougheed, Rik J. Scheper, Shabnam Samiei, Helen Gall, Karin Jooss, Jean-Marie Cuillerot, Natalie Sacks, Kirsten Hege, Winald R. Gerritsen, Alfons JM van den Eertwegh, Tanja D. de Gruijl. Inflammatory responses with infiltrating DC and functional cytotoxic T lymphocytes in the dermal vaccination sites of GVAX/ipilimumab treated prostate cancer patients. [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 496. doi:10.1158/1538-7445.AM2013-496
AB1105 Erythema nodosum: A retrospective study of 81 cases
Authors: R. Amel, B.F. Fatma, A. Jihed, K. Monia, L. Chadia
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Erythema nodosum (EN) is an inflammation of the fat cells under the skin (panniculitis) characterized by tender red nodules. EN is an immunologic response to a variety of different causes. <h3>Objectives</h3> The aim of this study is to evaluate the epidemiology, etiology, clinical manifestations, course, and prognosis of EN obseved in internal medecine <h3>Methods</h3> Over 13 years, patients with EN were included in a retrospective study. After a history and a physical examination, a clinical diagnosis was made according to well-established criteria. Statistical analysis was performed by SPSS 14 <h3>Results</h3> We have collected 81 cases. They were 11 males and 70 females. The mean age at presentation was 37.6 years (range: 14-77). 22% of patients had presented an anterior episode of EN. The nodules were situated at the legs (97.5%), the thighs (16%) and the upper limbs (24.5%). The EN was bilateral in 92.6% of cases. The EN was frequently associated with fever (62%), joint pain and inflammation (27%). In about 33% of cases, the cause of EN was unknown. Unless, it was a streptococcal infection (41%), tuberculosis (4%), medications (11%), Behçet's disease (6%), sarcoidosis (5%). Evolution under treatment was favorable and nodules of EN regressed within four weeks averagely. A recurrence of EN had occurred in 18.5% of cases. <h3>Conclusions</h3> EN is the most frequent clinico-pathological variant of the panniculitides, it may be associated with a wide variety of diseases requiring a minute etiological research. <h3>References</h3> Sang Won Yi and Al. Erythema Nodosum: Clinicopathologic Correlations and Their Use in Differential Diagnosis. Yonsei Med J. 2007 August 31; 48(4): 601–608. Requena L, Sánchez Yus E. Erythema nodosum. Semin Cutan Med Surg. 2007 Jun;26(2):114-25. Requena L, Yus ES. Erythema nodosum. Dermatol Clin. 2008 Oct;26(4):425-38, v. <h3>Disclosure of Interest</h3> None Declared
Abstract P2-13-03: Osteonecrosis of the Jaw: Dental Outcomes in Metastatic Breast Cancer Patients Treated with Bisphosphonates with/without Bevacizumab at Roswell Park Cancer Institute
Authors: N Ngamphaiboon, JL Frustino, EB Kossoff, MA Sullivan, TL. O'Connor
Journal: Cancer Research (2010)

Abstract Background: The etiology, optimal management, and long term outcome of osteonecrosis of the jaw (ONJ) is not well understood. Large trials have suggested that the combination of bevacizumab and bisphosphonates (BPs) does not significantly increase the incidence of ONJ. Because healing after mucosal trauma or dental surgery requires revascularization, it is possible that bevacizumab use could influence dental outcomes. Theoretically, the combination of bevacizumab and BPs may affect the time to development of ONJ and/or the response to dental therapy. Dental management of ONJ has not changed over time in our center, but increased recognition and screening may impact the dental outcome. Methods: We reviewed all cases of ONJ in metastatic breast cancer patients treated with BPs and with or without bevacizumab at Roswell Park Cancer Institute between October 2002 and April 2010. All patients diagnosed with ONJ discontinued BP therapy, while 3/7 (42%) continued bevacizumab until breast cancer progression. Type of BP, duration of treatment, total dose of BPs and bevacizumab dosing were recorded. All patients were treated in the department of dentistry with a combination of antibiotics, debridement, and chlorhexidine scrub. We evaluated the time to diagnosis of ONJ after the initiation of BP therapy, total dose of BP and dental treatment outcomes. Statistical analysis was performed using t-test and log-rank analysis. Results: See tables. 27 ONJ patients with a median age of 57 years (range 40-68) were analyzed. Patients were treated with zoledronic acid (95%), pamidronate (20%), or both (15%). 2 patients were excluded from dental response analysis due to lost follow up. Overall median time to ONJ treatment response was 5.0 months (range 1.3-67.5). Conclusions: The addition of bevacizumab to BP treatment did not significantly alter the time to the development of ONJ, the number of BP doses administered prior to diagnosis, or the response to dental treatment. However, ONJ response rates (complete and partial) to dental therapy have improved from 38% prior to 2007 to 58% after 2007, likely reflecting improved recognition and earlier treatment. Table.1 Time to ONJ and number of BP doses Table 2 ONJ response to dental treatments Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-13-03.
A case of rectal bleeding caused by digestive endometriosis resembling colon cancer
Authors: Bulent Yilmaz, Selma Cukur, Rula Sahin
Journal: Endoscopy (2014)

A 42-year-old unmarried, nulliparous woman presented at our hospital with rectal bleeding. The patient had had iron deficiency anemia in the past. She had normal, regular menses with mild dysmenorrhea and had not taken hormonal drugs. Her physical examination was unremarkable. Colonoscopy revealed widespread polypoid mucosal thickening and luminal narrowing, along with erythema and edema, in the sigmoid colon. It was not possible to pass the endoscope beyond the lesion ([Fig. 1]). Multiple endoscopic biopsies were taken, but histopathologic examination was nondiagnostic. An abdominal computed tomography (CT) scan revealed eccentric thickening of the wall of the sigmoid colon ([Fig. 2]).
Effect of Hospital Pay for Performance on Mortality in England
Authors: James G Wright
Journal: New England Journal of Medicine (2014)

cases and . . .timing of the lumbar puncture."We stated that "in six of seven patients with sporadic Creutzfeldt-Jakob disease in whom the RT-QuIC test of cerebrospinal fluid was negative but the RT-QuIC test of olfactory mucosa was positive, the lumbar puncture and olfactory mucosa brushing were performed at almost the same interval after disease onset, suggesting that the observed differences in prion seeding activity between these specimens were not due to differences in sampling time."We stand by this conclusion, although we now realize that the stated numbers pertain to total, rather than sporadic, Creutzfeldt-Jakob disease cases.Other, larger RT-QuIC analyses of cerebrospinal fluid specimens yielded sensitivities of 83 to 89%, 1,2 as compared with our provisional sensitivity of at least 97% from olfactory mucosa.Much further study is required, but since our initial report, we have collected these two specimen types simulta-neously from 12 additional patients, with a sensitivity of 100% from olfactory mucosa (12 of 12 samples) and 83% from cerebrospinal fluid (10 of 12 samples).
Website of the week: Breast problems
Authors: D Carnall
Journal: BMJ (1999)

The idea that life stress gives you cancer appeals to the intuition, but a paper in this issue shows that it has no scientific basis. As you might expect, web resources on breast problems abound.

It’s hard to tell who owns and writes the Breast Care Campaign’s site at www.breastcare.co.uk/index4.htm (and for this reason I would normally not bring it to your attention), but what is rather pretentiously known as the information architecture—the way the material is organised to enable the user to use it—is nicely done. The introductory information is easy to navigate; if you want the information on paper you can download a professionally designed patient leaflet in PDF format for easy printing.

The beauty of the web is that authors of localised information such as the Epping Breast Unit’s site at www.eppingbreast.ndirect.co.uk/ can choose to link from any one of a number of such sites, offering a personal gateway into the world of information that is out there. The 800 lb gorilla of cancer sites is the US National Cancer Institute’s Cancernet site at cancernet.nci.nih.gov/.

As well as obtaining information for patients and accessing a comprehensive resource on cancer trials in progress, you can send for a piece of software that enables you to calculate your risk of breast cancer (cancertrials.nci.nih.gov/NCI_CANCER_TRIALS/zones/Forms/NciSignUp_3.html). Hooking such tools to the web is a relatively simple job—although this has yet to happen to this particular piece of software—allowing a glimpse of an enticing future in which both doctors and patients harvest the information tools that they need from the web. In fact, it is happening already: you need to register to access some of the content on Breast Cancer On-line (usually another of my criteria for passing quickly by a site), but its well maintained page of high quality links (www.bco.org/p_links.htm) is obviously composed by someone who expects to check them all regularly.
The Bronchoconstrictor Effect of Inhaled Prostaglandin D2 in Normal and Asthmatic Men
Authors: Christopher Charles Hardy, Clive Robinson, Anne Elizabeth Tattersfield, Stephen Townley Holgate
Journal: New England Journal of Medicine (1984)

Although prostaglandin D2 is the most abundant prostanoid generated by human lung mast cells and causes bronchoconstriction in animals, its effects have not been studied in human beings. We have compared the effects of inhaled prostaglandin D2 and prostaglandin F2α on specific airway conductance in seven normal subjects and seven patients with mild allergic asthma. In dose–response studies in normal subjects, prostaglandin D2 caused a significant (20±6 per cent) fall in specific airway conductance after the two highest concentrations (250 and 500 μg per milliliter), whereas prostaglandin F2α had no effect. In the asthmatic subjects, both prostaglandin D2 and prostaglandin F2α caused a dose-related fall in specific airway conductance, starting at the lowest concentration of 4 μg per milliliter. Prostaglandin D2 was 3.5 times more potent than prostaglandin F2α. In a single-dose study of both drugs (250 μg per milliliter), a minor fall in specific airway conductance occurred with prostaglandin D2 in the normal subjects, and a larger fall occurred with both drugs in the asthmatic subjects. Maximum effects were seen at three minutes: there was a 75±5 per cent fall with prostaglandin D2 and a 33±8 per cent fall with prostaglandin F2α. These results suggest that prostaglandin D2 may be involved in the pathogenesis of bronchoconstriction in allergic asthma. (N Engl J Med 1984; 311:209–13.)
AB0274 The Influence of Continuous Remission Rate on Functional Disability and Radiographic Progression for Rheumatoid Arthritis in A Japanese Observational Cohort
Authors: M. Furu, M. Hashimoto, H. Ito, T. Fujii, M. Ishikawa, N. Yamakawa, C. Terao, H. Yoshitomi, H. Ogino, S. Matsuda, T. Mimori
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> One goal of clinical remission in rheumatoid arthritis (RA) is to halt joint damage. The continuous clinical remission in established RA may result in improved function and reduced radiographic progression. <h3>Objectives</h3> The authors assessed disease activity, functional disability and the progression of radiographic joint damage among RA patients in our Japanese observational cohort, and evaluated the relationship between continuous clinical remission and both functional disability and radiographic progression. <h3>Methods</h3> We chose the 200 of consecutive RA patients, both with more than 6 months and with more than three visits during follow-up, and assessed clinical variables. The continuous remission rate over the entire period was defined, and assessed in comparison with the rate of functional remission and rapid radiographic progression (RRP). <h3>Results</h3> The continuous remission rate was 38.9%, 23.7% and 25.7% for DAS28, CDAI and SDAI, respectively (table). The functional remission was achieved in 66.2%, 80.9% and 77.1% patients who fulfilled over 50% as continuous remission rate for DAS28, CDAI and SDAI, respectively (figure). RRP was observed in 27.6%, 25.0% and 30.0% patients who fulfilled less than 50%, and in 7.7%, 2.6% and 0% patients more than 50% as continuous remission rate for DAS28, CDAI and SDAI, respectively. <h3>Conclusions</h3> SDAI and CDAI remission were more stringent for functional and radiographic assessment than DAS28 remission. The continuous clinical remission was associated with improved function and reduced radiographic progression in RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2782