tbuckley/cabot-search huggingface dataset:
Milk-Precipitating Substance in the Stool in Gastrointestinal Milk Sensitivity
Authors: Julian Katz, Howard M. Spiro, Teodoro Herskovic
Journal: New England Journal of Medicine (1968)

An association between the presence in the stool of precipitating substances to cow's milk and the occurrence of milk-induced gastrointestinal bleeding, protein loss and diarrhea was demonstrated in four children. This precipitating substance was not found in the stools of patients with a variety of diarrheal and other disorders. It is suggested that an antigen-antibody reaction is involved in the precipitation of milk protein by the fecal substance and that this substance is a coproantibody. No precipitins to milk proteins were detected in their serums, but titers to alpha lactalbumin were high in three of the four children. Immunologic mechanisms may be involved in gastrointestinal milk sensitivity, although the role of antibodies in the pathogenesis of the disorder might only be a secondary one.
Abstract SY41-01: Tumor-endothelial transdifferentiation
Authors: Inder M. Verma, Yasushi Soda, Dinorah Friedmann-Morvinski, Sandra Pastorino, Santosh Kesari
Journal: Cancer Research (2012)

Abstract Glioblastoma (GBM) is the most malignant brain tumor and highly resistant to intensive combination therapies and anti-VEGF therapies. To assess the resistance mechanism to anti-VEGF therapy, we examined the vessels of GBMs in tumors that were induced by the transduction of p53+/− heterozygous mice with lentiviral vectors containing oncogenes and the marker GFP in the hippocampus of GFAP-Cre recombinase (Cre) mice. We were surprised to observe GFP+ vascular endothelial cells (ECs). Transplantation of mouse GBM cells revealed that the tumor-derived endothelial cells (TDECs) originated from tumor-initiating cells and did not result from cell fusion of ECs and tumor cells. An in vitro differentiation assay suggested that hypoxia is an important factor in the differentiation of tumor cells to ECs and is independent of VEGF. TDEC formation was not only resistant to an anti-VEGF receptor inhibitor in mouse GBMs but it led to an increase in their frequency. A xenograft model of human GBM spheres from clinical specimens and direct clinical samples from patients with GBM also showed the presence of TDECs. We suggest that the TDEC is an important player in the resistance to anti-VEGF therapy, and hence a potential target for GBM therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY41-01. doi:1538-7445.AM2012-SY41-01
RT-01 * FRACTIONATED STEREOTACTIC RADIOTHERAPY FOR PITUITARY ADENOMA WITH NOVALIS
Authors: Y. Arakawa, T. Mizowaki, K. Ogura, K. Sakanaka, M. Hojo, M. Hiraoka, S. Miyamoto, D. Murata
Journal: Neuro-Oncology (2014)

BACKGROUND: Radiation therapy is an available treatment modality for pituitary adenoma. In particular, it is effective for the case unable to be removed with surgery or repeating recurrence. However, hypopituitarism and optic nerve injury associated with radiation therapy become a problem. Novalis® (Brain Lab) is an equipment of radiation to establish the detailed irradiation area, fractionated stereotactic radiotherapy (fSRT) and intensity-modulated radiation therapy (IMRT). Retrospectively, we review local control and morbidity following fSRT with Novalis in pituitary adenoma. PATIENTS AND METHODS: Between 2007 and 2012, 29 patients with pituitary adenoma (9 functioning, 20 non-functioning) received fSRT with Novalis in our institute. Total radiation dose was 50.4-54Gy (1.8 Gy per fraction) and prescribed to the gross target volume + 2 mm. The effectiveness of fSRT was evaluated by tumor volume and clinical symptoms on pre- fSRT, and every 1-year. RESULTS: The median follow-up time was 59.1 months (20 to 83 months). Tumor regrowth was observed in 2 cases. Progression free survival rate was 93%. New visual field deficit was observed in 1 case, and new pituitary dysfunction were not observed in all patients. CONCLUSION: fSRT with Novalis is safe and effective in the treatment for pituitary adenoma. Although follow-up time is short, any problematic complications were not observed. In the future, fSRT is expected to make for safe and effective treatment in pituitary adenoma impossible to cure surgically.
Abstract 382: Platelets are implicated in the rapid host responses induced by cytotoxic chemotherapy which limit its anti-tumor efficacy
Authors: Chlöe C. Milsom, Yuval Shaked, Christina R. Lee, Shan Man, Robert S. Kerbel
Journal: Cancer Research (2010)

Abstract Previous studies from our lab have shown that the overall anti-tumor impact of certain cytotoxic drugs such as paclitaxel (PTX) given at maximum tolerated doses (MTDs) or OXi-4503, a microtubule inhibiting vascular disrupting agent (VDA), can be reduced by a rapid systemic counter-acting host response (Y Shaked et al., Science 2006 and Cancer Cell 2008). The aforementioned host response includes rapid induction of elevated plasma levels of multiple cytokines or chemokines such as G-CSF and SDF-1, which can promote mobilization and tumor-homing/colonization of proangiogenic and tumor-growth promoting bone marrow-derived cells (BMDCs), including circulating endothelial progenitor cells. This reactive host response promotes recovery/repopulation of the drug treated tumor. Here we asked what might be the source(s) of the elevated levels of plasma chemokines and cytokines induced by MTD PTX. We found platelets - known major sources of SDF-1 and VEGF - become activated and release the contents of their alpha granules into the circulation (plasma), such that decreases in platelet associated SDF-1 (and VEGF) are observed accompanied by increases in their plasma levels. SDF-1 is known to mobilize a variety of BMDCs including CEPs. Because platelets are not known to be a source of G-CSF - which is also elevated in the plasma by MTD PTX - other cellular and/or non-cellular sources are likely affected as well by the drug treatment. We also found that pharmacologic-mediated reductions in platelet numbers or activation results in reduced expression of the counter-acting host cytokine/chemokine response induced by MTD PTX treatment, thus providing further support for a contribution of platelets. Finally we have found low-dose metronomic chemotherapy does not induce the counter acting host response which is likely due in part to a lack of effect on platelets. In summary, our results implicate a new way in which platelets can impact tumor biology and response to therapy. 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 382.
PWE-115 Patients Continue To Travel Abroad Despite Recently Active Disease And Travel Concerns: Results Of A Single Centre Study In Inflammatory Bowel Disease And Travel
Authors: TC Shepherd, K Greveson, JP Mulligan, MI Hamilton, CD Murray
Journal: Gut (2014)

<h3>Introduction</h3> Travellers with Inflammatory bowel disease (IBD) are at greater risk of travel-related morbidity.<sup>1</sup> Relapse and acquired infection are the main risks to IBD patients while abroad, and ECCO recommend expert consultation prior to travel, particularly for those on immunosuppression.<sup>2</sup> IBD limits a majority of patients choice of travel destination.<sup>1</sup> Despite this, there is limited data regarding IBD patients pre-travel preparation and travel experiences. <h3>Methods</h3> Patients attending our IBD clinic during November 2013 were asked to complete an anonymous questionnaire. We asked for demographic and disease specific information, in addition to detailed travel questions; including perceptions, pre-travel planning and recent travel experiences. Data was entered and analysed on an anonymised database. We hypothesised that patients with travel concerns and those who had flared within the last 6 months would be less likely to go abroad in that same period. <h3>Results</h3> A representative 136 IBD patients (67/136[49%] Crohn’s disease, 60/136[44%] male, age 18–85 years [median age 38 years]) responded. 51%[69/136] were immunosuppressed and 43%[49/136] had IBD related surgery. 62%[84/136] experienced an IBD flare in the last 6 months. 60%[82/136] reported IBD affected travel. 58%[79/136] travelled in the last 6 months, despite a majority of those (65%[51/79]) reporting IBD affected travel. 59%[47/79] of travellers had experienced a flare in the last 6 months, although again, most of those (77%[36/47]) reported IBD affected travel. Only 18%[14/79] travellers (71%[10/14] had a recent flare) sought pre-travel medical advice of any kind and only 41%[32/79] (69%[22/32] had a recent flare) had travel insurance, the majority (88%[28/32]) paid a premium. 20%[16/79] travellers reported a change in bowel habit while abroad, but of those only 27%[3/11] sought medical advice. We also report that 52%[36/69] of immunosuppressed patients are unaware of the need to avoid live vaccines. <h3>Conclusion</h3> A majority of IBD patients feel their disease affects travel. However, despite concerns, patients still travel abroad, even if they have suffered a recent flare. Our results suggest patients are not receiving the recommended travel medical advice, including the need to avoid live vaccinations if immunosuppressed, and are possibly under or not insured. The small numbers of travellers suffering a change in bowel habit abroad tend not to seek medical advice while away. Further detailed investigation in travel behaviour in IBD patients is required, but we suggest there is a need for greater IBD travel education. <h3>References</h3> Soonawala D, <i>et al</i>. <i>Inflamm Bowel Dis</i> November 2012;18(11):2079–85 Rahier JF, <i>et al</i>. <i>J Crohn Col</i> February 2009 <h3>Disclosure of Interest</h3> None Declared.
FRI0593-HPR Translation, cultural adaptation and reproducibility of the michigan hand outcomes questionnaire (MHQ) for brazil
Authors: S. M. M. Adolph, J. Natour, D. A. Batista, M. Lopes, T. L. Skare
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects all synovial joints causing progressive and irreversible joint destruction. Hand dysfunction and deformities are some of the most common manifestations of this disease and they are an important cause of morbidity as they interfere with the capacity to perform self care, work productivity and social interactions. MHQ (Michigan Questionnaire of Hand Evaluation) is a hand evaluation instrument that has been conceived at University of Michigan in 1998 using psychometric principles <h3>Objectives</h3> To translate to Portuguese, to perform cultural adaptation and to test the reliability of the questionnaire Function Hand Outcomes Questionnaire hand Michigan (MHQ) for use in the Brazilian population. <h3>Methods</h3> In the first stage of the study, the MHQ was translated into Portuguese and back translated into English. The Portuguese version was tested in 30 patients with rheumatoid arthritis with some involvement in hand or wrist and the questionnaire proved to be understandable and culturally adapted. In a second stage of the study, 30 patients with rheumatoid arthritis with hand or wrist affected were evaluated 3 times. In the first two evaluators applied the MHQ to check intra rater reliability. After 15 days, one of the evaluators reinterviewed the patients to verify inter-rater reproducibility. To check the construct validity at the the first assessment, one of the evaluators also applied other instruments such as DASH (Disability of the Arm, Shoulder and Hand questionnaire), HAQ (Health Assesment Questionnaire), VAS (Visual Analogic Scale) of pain and COCHIN Hand Function Scale. <h3>Results</h3> We observed strong inter and intra rater correlations in all areas of the MHQ. Intra rater concordance ranged from 0.84 to 0.96 and inter rater correlations ranging from 0.61 to 0.92. The Cronbach's alpha was higher than 0.90 for all domains of the MHQ indicating that the questionnaire had good internal validity. Almost all domains of the MHQ evaluation applied to the dominant hand presented moderate and strong correlation (r ranging from -0.50 to -0.89) with other instruments showing a good construct validity. <h3>Conclusions</h3> The Brazilian Portuguese version of the MHQ was translated, culturally adapted successfully and showed very good internal consistency, reliability and construct validity. <h3>Disclosure of Interest</h3> None Declared
Abstract 1632: Anti-β1 integrin antibody inhibits osteosarcoma lung seeding and metastasis
Authors: Hiroaki Kimura, Yasunori Tome, John Grzesiak, Masashi Momiyama, Katsuhiro Hayashi, Michael Bouvet, Hiroyuki Tsuchiya, Robert M. Hoffman
Journal: Cancer Research (2011)

Abstract The efficacy of anti β1 integrin monoclonal antibody (clone AIIB2) to inhibit lung seeding and colony formation of human osteosarcoma cells was imaged in real time. To visualize cancer cell seeding and metastasis in the lung, human osteosarcoma cells were used in which green fluorescent protein (GFP) is expressed in the nucleus and RFP is expressed in the cytoplasm. 143B cells were preincubated with AIIB2 or control antibody, and then injected into the nude mice via tail vein. Twenty four hours later, the lungs were fluorescently-imaged in live mice with the lung exposed. 143B cells which arrested in the lung were counted. Two weeks after the first observation, the animals were sacrificed and the lungs were resected and fluorescently imaged to quantitate resulting lung metastatic colonies. AIIB2 significantly inhibited osteosarcoma cells seeding and colony formation in the lung. This result indicates that β1 integrin plays an important role for osteosarcoma cell adhesion to lung. To evaluate efficacy of the AIIB2 antibody on primary tumor growth and spontaneous metastases, 143B osteosarcoma cells were orthotopically transplanted in the tibia. Two weeks later, mice were treated with either 40 µg or 200 µg AIIB2, or control antibody biweekly. After three weeks treatment, primary tumors and lung metastases were evaluated. Neither 40 µg nor 200 µg of AIIB2 significantly inhibited primary tumor growth. In contrast, both doses of AIIB2 significantly inhibited spontaneous lung metastasis. AIIB2 appears to be a specific anti-metastatic agent since it inhibited lung metastasis while not inhibiting primary tumor growth. This is consistent with AIIB2 inhibition of adhesion of 143B cells to the lung. These results suggest that anti-β1 integrin antibody treatment has clinical potential as an anti-metastatic agent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1632. doi:10.1158/1538-7445.AM2011-1632
Fixed Drug Eruption
Authors: Isabel Cristina Valente Duarte de Sousa
Journal: New England Journal of Medicine (2011)

A 35-year-old man presented with a 10-day history of a cutaneous lesion on the left anterior chest. Examination revealed an annular, scaly, blistering, violaceous plaque, 5 cm in diameter, with an erythematous periphery. The lesion had appeared 24 hours after the patient began a self-prescribed course of oral trimethoprim–sulfamethoxazole for a respiratory tract infection. Six months earlier, an identical lesion had appeared in the same location after the patient had taken the same drug for 3 days. This first lesion healed after 3 weeks, but residual hyperpigmentation remained. On the basis of this characteristic presentation, a diagnosis of fixed drug . . .
STAT5 Loss Awakens the Dark Force in Natural Killer Cells
Authors: Jing Ni, Adelheid Cerwenka
Journal: Cancer Discovery (2016)

Abstract Summary: Natural killer cells (NK) are commonly considered to be potent antitumor effector cells. The study by Gotthardt and colleagues challenges this concept and reveals that STAT5-deficient/inhibited NK cells induce angiogenesis and promote tumor progression. These unexpected findings shed new light on potential adverse effects of JAK–STAT inhibitors in the clinics. Cancer Discov; 6(4); 347–9. ©2016 AACR. See related article by Gotthardt et al., p. 414.
Bone morphogenetic protein 2 (BMP-2) and induction of tumor angiogenesis
Authors: M. Raida, J. H. Clement, R. D. Leek, K. Ameri, R. Bicknell, A. L. Harris
Journal: Journal of Clinical Oncology (2004)

9531 Background: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta family and act as multifunctional proteins that regulate cell proliferation and differentiation. They play an important role in the regulation of embryonic vasculogenesis but their role in postnatal angiogenesis remains to be clarified. Recently, we have shown that BMP-2 protein expression is reactivated in breast cancer. In this study we investigated a possible role of BMP-2 in the promotion of tumor angiogenesis. Methods: We studied the effect of BMP-2 on human dermal microvascular endothelial cells (HDMECs) and examined a possible angiogenic activity of BMP-2 with the mouse sponge assay. The effect of BMP-2 overexpression on tumor vascularization was also analysed in xenografts of human BMP-2 transfected MCF-7 breast cancer cells (MCF7/BMP2) in mice. Results: BMP receptor activation induced selectively the phosphorylation of p38 mitogen activated protein kinase (MAPK) in contrast to the ERK1/2 MAP kinases. In keeping with this finding BMP-2 had no significant effect on endothelial cell proliferation but promoted HDMEC tube formation in the matrigel assay. The basic-helix-loop-helix transcription factor inhibitor of differentiation 1 (Id1) which is known to play an important role in neovascularization of tumors was identified as a BMP target in HDMECs. Immunohistochemical analysis of sponge sections revealed that BMP induced vascularization. Treatment with VEGF in addition to BMP-2 showed a synergistic enhancement of angiogenesis. In the murine breast cancer xenograph model human MCF7 cells with stable overexpression of BMP-2 formed tumors that were characterised by an enhanced vasculature. Conclusions: We conclude that activation of the BMP pathway by BMP-2 can promote vascularization and might be involved in tumor angiogenesis possibly by activating the Id1 pathway. No significant financial relationships to disclose.
PM-10 * CDCA7L FUNCTIONS AS A MALE-SPECIFIC ONCOGENE IN ASTROCYTOMA
Authors: M.-H. Lee, K. Reilly
Journal: Neuro-Oncology (2014)

The most common types of primary brain tumors, astrocytoma and glioblastoma multiforme (GBM), are currently incurable. Both astrocytoma and GBM show male predominance, with a male to female ratio of 1.42:1 and 1.58:1, respectively. We performed linkage analysis in the Nf1-/ + ;Trp53-/ + cis (NPcis) mouse model of astrocytoma/GBM to identify a male-specific gliomagenesis modifier and further used combinatorial bioinformatics approaches as well as cross-species comparisons to prioritize male-specific candidate gene(s). Here, we showed that Cell division cycle-associated 7-like (CDCA7L), a myc cotranscription factor, is a male-specific oncogene in astrocytoma/GBM. CDCA7L expression is up-regulated in astrocytoma cells compared to normal brain, with males showing higher levels than females in both human and mouse. shRNA-mediated CDCA7L knockdown led to the decreased cell growth and viability of male-derived astrocytoma cells, but not female tumor cells in both human and mouse. Further mechanistic studies showed that CDCA7L depletion in male-derived astrocytoma cells led to the induction of cleaved Caspase-3 and p27 expression and reduction of Cyclin D1 expression. Furthermore, Cdca7l overexpression promotes the growth of WT mouse primary astrocytes only in males by inducing Cyclin D1 expression, but not in female astrocytes, suggesting a male-specific oncogenic role for CDCA7L in astrocytoma/GBM. Strikingly, CDCA7L depletion in human female U87MG GBM cells caused the increase of both growth and viability opposite to what is seen in male cells. Because male-female differences in CDCA7L action are hormone-independent, we examined whether the male-specific histone demethylase KDM5D regulates the effects of CDCA7L. We found that knockdown of KDM5D inhibits male-specific effects of CDCA7L on p27 and Cyclin D1 expression. Our data highlight the sex-specificity of CDCA7L in astrocytoma/GBM tumorigenesis and show that CDCA7L signaling pathways can be oncogenic in males, while being neutral or tumor suppressive in females. This has important implications for the application of therapies to human GBM patients.
The Incidence of Hypertension in Mitral Stenosis
Authors: Melvin D. Roseman, Edward Wasserman
Journal: New England Journal of Medicine (1951)

FORTY-TWO years ago Gibson,1 in writing about the arterial pressure in mitral stenosis, stated: "It is often below the normal but even more frequently above it." In 1912 Cowan and Fleming2 discussed the association between mitral stenosis and renal fibrosis and concurred with Gibson's Statement. Several years later, Coombs3 also stated that in mitral stenosis a "raised pressure is not uncommon." He reported that 3 of 16 patients with mitral stenosis had hypertension. Since then, several conflicting reports concerning the incidence of hypertension in mitral stenosis have appeared in the literature.The purpose of the present study is to reinvestigate . . .
Cutaneous Xanthomas in Homozygous Familial Hypercholesterolemia
Authors: J L Teruel, M A Lasunción
Journal: New England Journal of Medicine (1995)

Figure 1. A baby boy was found to have familial hypercholesterolemia at the age of six months. His parents also had hypercholesterolemia. Seven and a half years later, studies of the activity of low-density lipoprotein (LDL) receptors in proliferating lymphocytes indicated that the parents were heterozygous and the child was homozygous for LDL-receptor deficiency. The child's serum cholesterol concentration ranged from 850 to 1000 mg per deciliter (22 to 26 mmol per liter), and he had cutaneous xanthomas on his knees (as shown), elbows, and interdigital folds. Because the hypercholesterolemia was refractory to treatment with lovastatin and cholestyramine, the patient . . .
F-18 FDG PET/CT Imaging and Bronchoscopic Image of Tracheal Recurrence in Patient With Non–Small-Cell Lung Cancer
Authors: Bala Basak Oven Ustaalioglu, Umut Kefeli, Ahmet Bilici, Recep Ustaalioglu, Mesut Seker, Ferahnaz Cinaral, Ilgaz Dogusoy
Journal: Clinical Nuclear Medicine (2011)

We report tracheal recurrence in patient with non–small-cell lung cancer (NSCLC) who was diagnosed with F-18 fluorodeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT) during follow-up period. A 56-year-old man presented with mediastinum involvement of NSCLC (clinical stage IIIA). After 3 cycles of neoadjuvant platinum-based chemotherapy, he underwent right pneumonectomy. Because tumor in the right main bronchus was located <2 cm distal to the carina, pathologic stage IIB (T3N0M0) disease was diagnosed according to seventh addition of American Joint Committee on Cancer (AJCC) TNM classification. Thereafter, adjuvant 3 cycles of chemotherapy was administered. At the 21st month of follow-up period, he presented with dyspnea and inspiratory stridor. FDG PET/CT was performed and it revealed multiple intense uptake foci in the trachea (SUVmax = 10.1) compatible with malignant tracheal nodules. After rigid bronchoscopy and biopsy were carried out, tracheal recurrence was confirmed. We conclude that it would be interesting to investigate the use of FDG PET/CT in the work-up of tracheal recurrence of NSCLC. Tracheal recurrence was confirmed with rigid bronchoscopy and biopsy.