tbuckley/cabot-search huggingface dataset:
Potentiation of Antitumor Activity of Vincristine by the Biscoclaurine Alkaloid Cepharanthine
Authors: T Kato, Y Suzumura
Journal: JNCI Journal of the National Cancer Institute (1987)

A membrane stabilizer, the biscoclaurine alkaloid cepharanthine markedly enhanced the cytotoxicity of vincristine (VCR) and adriamycin in cultured L1210 cells at a noncytotoxic dose. When 0.1-0.5 micrograms cepharanthine/ml was added along with VCR to L1210 cells in vitro, the cytotoxicity of VCR was potentiated 1.5-fold to 7-fold, whereas such potentiation was not found in mitomycin C, bleomycin, and 5-fluorouracil. The potentiating action of cepharanthine was stronger when the cells were preincubated with cepharanthine prior to the treatment of cells with VCR and cepharanthine, suggesting that a long-term contact with cells is required for the enhancement. Cepharanthine was found to induce the increase of the cellular level of VCR in L1210 cultured cells. It was suggested that the accumulation of VCR is due to the inhibition of a VCR efflux function of the cells. The administration of cepharanthine at the dose of 5 mg/kg/day for 10 days with VCR significantly enhanced the antitumor activity of VCR in L1210 leukemia and P388 leukemia (P less than .025). However, the combined effect of cepharanthine and VCR in this regimen was marginal synergism. When the same dose of cepharanthine was administered in split administration, three times daily for 10 days, the therapeutic effect of VCR was further enhanced compared to its effect under the former regimen. Furthermore, cepharanthine was found to partially overcome the resistance of VCR in P388/VCR.
Hypertensive Crisis since FDR — A Partial Victory
Authors: David A. Calhoun, Suzanne Oparil
Journal: New England Journal of Medicine (1995)

Accelerated, or malignant, hypertension is a disorder whose natural history has been so greatly changed by the availability of effective diagnosis and therapy that many physicians no longer encounter it. In this issue of the Journal, Messerli recalls the progressive deterioration and death from untreated hypertension of President Franklin D. Roosevelt.1 Over a period of 10 years, Roosevelt progressed from having what is now termed “high-normal blood pressure” to having very severe (stage 4) hypertension complicated by left ventricular enlargement and proteinuria. He had untreated heart failure during the most critical period of World War II and died of an . . .
SP0076 Proteasome as A Therapeutic Target in Osteoarthritis?
Authors: A. Ahmed
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Osteoarthritis (OA) is a common chronic joint disorder affecting approximately 10% of the population today. Pain is the predominant symptom in patients with OA followed by changes in articular cartilage, subchondral bone, synovial membrane and adjacent supporting connective tissues. The mechanisms of pain in OA remain obscure and the current treatments are mainly symptomatic to reduce the pain and joint replacement surgery at the end stage of disease. Thus, the mediators and mechanisms that monitor pain and inflammation in OA are of great interest in search for new treatment modalities in OA. The ubiquitin proteasome system (UPS) is one of the recently highlighted systems participating in the mechanisms of pain and inflammation through its effects on pro-nociceptive and pro-inflammatory mediators. UPS is a non-lysosomal proteolytic system of selective degradation of intracellular proteins. It plays an essential role in the activation of transcription factor-κB (NF-κB) through proteolytic degradation of inhibitory protein IκB. NF-κB in turn activates pro-nociceptive and pro-inflammatory mediators such as cytokines and neuropeptides involved in pain and inflammation. Furthermore, UPS-mediated protein degradation promotes osteoclast maturation, which induces cartilage and bone destruction in inflammatory joint disorders such as rheumatoid arthritis and OA. Recently, we have demonstrated that the inhibition of the UPS by synthetic small molecule, MG132, reduced severity of arthritis and reversed joint pain behavior in animal model of OA. In addition, MG132 therapy reversed the up-regulated expression of pro-nociceptive sensory neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in knee joint as well as in the dorsal root ganglion, a site of neuropeptide synthesis. Increased levels of SP are reported in the capsule of hip joints and soft tissues in patients with painful OA. MG132 therapy attenuated cartilage and bone destruction and resulted in decreased matrix metalloproteinase -3 (MMP-3) expression in OA knee joint. MMPs, especially MMP-3, exacerbate pathogenesis of OA through proteoglycans degradation. MMP-3 synthesis is regulated by the NF-κB, the activation of which is under the control of UPS. A robust effect with reversal of pain behavior, attenuated cartilage destruction and decreased SP, CGRP and MMP-3 expression suggest that UPS is one of the intracellular pathways critical for the development of both pain and joint destruction in animal model of OA. Proteasome system may represent a promising system/mechanism for treatment modality in OA. Thus, novel safe proteasome inhibitors with limited adverse effects would be beneficial to attenuate the development of arthritis and hence reduce the pain. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6331
P3-03-08: microRNAs in Mammary Stem-Like Cells and Triple-Negative Breast Cancer; Conserved Functions and Treatment Potential.
Authors: C Williams, E Aydogdu, A Katchy, C-Y Lin, L-A Baldosen, L Helguero
Journal: Cancer Research (2011)

Abstract Background: Mammary stem and progenitor cells are thought to be precursors of different subclasses of breast cancer. Triple-negative breast cancer exhibit similarities to stem or progenitor-like cells. microRNAs (miRNAs) play pivotal roles in both stem cell biology and oncogenesis. Given their potential as therapeutic targets, little is known, however, regarding miRNAs expression and functions in normal and breast cancer cells. Our objective was to identify which miRNAs are involved in mammary stem cell maintenance and differentiation and study their potential roles in triple-negative breast cancer. We investigated their expression during induced differentiation of mammary stem-like cells, correlated their expression to that of triple-negative breast cancer cells and studied the functions of the most regulated and conserved candidates. Material and Methods: Using large-scale profiling and extensive qPCR confirmation we defined miRNAs regulated during stem-like cell differentiation. We investigated their expression in different breast cancer cell lines, and performed functional studies using miRNA mimics and inhibitors in normal stem-like cells and triple-negative breast cancer cells. Results: Twenty-one miRNAs were strongly regulated in repeated rounds of mammary cell differentiation. The majority, including the miR-200 family and known tumor suppressor miRNAs, was upregulated during differentiation. Only 4 miRNAs, including the oncomiR, miR-17, were upregulated in the stem cell-like stage. Pathway analysis indicated complex interactions between regulated miRNA clusters and major pathways regulated during this transition, including stem cell maintenance, proliferation and differentiation. The cell model used exhibited gene expression profiles resembling basal-like poor prognosis breast cancer. Morover, we present data of miRNAs that target the genes and networks responsible for this correlation. miRNAs detected in this study can also differentiate between human non-cancer and breast cancer cell lines, and a subclass of miRNAs, was specifically downregulated in a basal-like breast cancer cell line. The functions of five miRNAs (miR-200a, -200b, -146b, -148a and -206) were further investigated. Discussion: Our findings suggest that the identified miRNAs have significant roles in biological pathways and networks associated with mammary stem/progenitor cell maintenance and triple-negative breast cancer and support their further evaluation as potential prognostic markers and therapeutic targets in the treatment of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-03-08.
Unusual Bilateral Symmetrical Osteolytic Metastases Visualized by Bone Scintigraphy
Authors: MADHUSUDHAN P. REDDY, JOSEPH FLORESCA, MALIK JUWEID, MICHAEL M. GRAHAM
Journal: Clinical Nuclear Medicine (2002)

REDDY, MADHUSUDHAN P. M.D.; FLORESCA, JOSEPH M.D.; JUWEID, MALIK M.D.; GRAHAM, MICHAEL M. Ph.D. M.D. Author Information
Abstract 2028: miR-433 attenuates the spindle assembly checkpoint (SAC) response to paclitaxel
Authors: Fiona M. Furlong, Maria Prencipe, Alo McGoldrick, Paul McGettigan, Desmond Carney, Emma Doyle, Elaine Kay, Amanda McCann
Journal: Cancer Research (2010)

Abstract Paclitaxel is a microtubule inhibitory chemotherapeutic drug which is increasingly used for the treatment of solid tumours. In vitro studies have demonstrated that attenuating the spindle assemble checkpoint (SAC) alters the post-mitotic responses to paclitaxel. Furthermore, the aberrant expression of a number of the SAC proteins, MAD2, BUBR1, and Aurora A kinase, are associated with poor patient prognosis. We have identified a microRNA, miR-433, that regulates the expression of MAD2. Over-expression of miR-433 in HeLa cells induced downregulation of MAD2 mRNA and protein expression. We have also shown that HeLa cells over-expressing miR-433 and treated with paclitaxel are no longer capable of cyclin B stabilisation and thus have lost the ability to activate the SAC in response to paclitaxel. In addition, cell viability assays showed that HeLa cells over-expressing miR-433 and treated with paclitaxel have an attenuated response to pacilitaxel compared to microRNA scrambled controls. We have characterised the levels of miR-433, MAD2 gene expression and MAD2 protein levels in a cohort of ovarian cancer cell lines. Cell viability assays on this cohort revealed that responsiveness to paclitaxel is associated with high MAD2 protein expression and low miR-433 expression. We hypothesise that the expression of miR-433 when deregulated in cancer leads to altered MAD2 expression and a compromised SAC, a key feature underlying drug resistance to paclitaxel. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 2028.
An Outbreak in 1996 of Cyclosporiasis Associated with Imported Raspberries
Authors: Barbara L. Herwaldt, Marta-Louise Ackers
Journal: New England Journal of Medicine (1997)

Cyclospora cayetanensis is a parasite that causes gastroenteritis. Until last year most of the documented cases of cyclosporiasis in North America were in overseas travelers. In 1996, a large outbreak of cyclosporiasis occurred in North America. We investigated this outbreak.
P14.06 * MOBI-KIDS STUDY: EXPOSURE TO COMMUNICATION TECHNOLOGIES AND BRAIN TUMOUR RISK IN CHILDREN AND ADOLESCENTS
Authors: M. M. Maule, E. Cardis, C. Eastman Langer, S. Sadetzki, G. Filippini, M. Farinotti, L. Miligi, S. Mattioli, F. Merletti
Journal: Neuro-Oncology (2014)

The rapid worldwide increase in mobile phone use and the often controversial results of the studies on their possible health effects has generated considerable concern in the public, especially when considering the increasing exposure of children and adolescents. MOBI-Kids, a prospective case-control study conducted in 15 countries and spanning a target population of almost 40 million individuals, was initiated to assess the potential effects of exposure to radiofrequency fields (RF) and extremely low frequency fields (ELF) from mobile phones on the development of central nervous system tumours among people aged 10 to 24 years old. This study faces a high level of complexity and methodological challenges, including the need to reduce potential bias, heterogeneity of the malignancies affecting people in this age range, strict ethic legislations, and assessment of exposure to RF and ELF. The study builds upon the experience of INTERPHONE, the 13-country study investigating mobile phone use and risk of brain cancer in adults in 2000-2004. It aims to include approximately 1,000 brain tumour cases and 2,000 matched controls. Such numbers will ensure 80% power to detect an increased risk of 40% assuming 10% have used a mobile phone for 10 years or longer. An interview is administered to all participants and their parents to assess lifestyle, residential, occupational and school history, use of communication technologies, exposure to environmental risk factors, medical history and family history of cancer. Reported mobile phone use is validated with phone records provided by operators. Biological samples for DNA isolation are collected in several countries. Clinical data and images needed for diagnosis verification and tumour classification are collected from all available medical files. Tumour images will be mapped on 3D head models by neuroradiologists. MOBI-Kids started on the Feb 1st, 2009, and cases' recruitment is scheduled to finish at the end of 2014. To date, 790 cases and 1958 controls have been identified. Of these, 587 cases and 1059 controls answered the full questionnaire, 101 answered a short non response questionnaire on mobile phone use and socioeconomic status, which will be used to assess potential selection bias. MOBI-Kids results, by contributing to the understanding of potential brain tumour risks associated with the use of mobile phones and other communication technologies among young people, will have a strong impact in terms of public health and protection of the population.
Abstract 484: Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells.
Authors: Hidekazu Shirota, Yuko Shirota, Dennis M. Klinman
Journal: Cancer Research (2013)

Abstract Immunostimulatory CpG oligonucleotides (ODN) activate cells that express TLR9 and have been shown to improve the host's response to tumor Ags. Unfortunately, the immunosuppressive microenvironment that surrounds many cancers inhibits Agspecific cellular responses and thus interferes with CpG-mediated immunotherapy. Myeloid-derived suppressor cells (MDSC) represent an important constituent of this immunosuppressive milieu. Large numbers of MDSC are present in and near tumor sites where they inhibit the activity of Ag-specific T and NK cells. Current studies indicate that the delivery of CpG ODN directly into the tumor bed reduces the immunosuppressive activity of monocytic (CD11b+, Ly6G-, Ly6Chigh) MDSC. Monocytic MDSC express TLR9 and respond to CpG stimulation by 1) losing their ability to suppress T cell function, 2) producing Th1 cytokines, and 3) differentiating into macrophages with tumoricidal capability. These findings provide insight into a novel mechanism by which CpG ODN contribute to tumor regression, and they support intratumoral injection as the optimal route for their delivery. Citation Format: Hidekazu Shirota, Yuko Shirota, Dennis M. Klinman. Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells. [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 484. doi:10.1158/1538-7445.AM2013-484 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
PTH-136 A Myriad Of Causes For Diarrhoea In Patients Presenting At A Giant (gi And Nutrition Team) Clinic In A Cancer Centre
Authors: A Muls, J Andreyev
Journal: Gut (2014)

<h3>Introduction</h3> Better cancer treatments have led to enormous improvements in the outcomes for these patients with the result that the overall number of survivors of cancer therapy continues to grow. However, after cancer treatment, up to 50% patients are left with diarrhoea - the most prevalent symptom. Causes are likely to encompass several contributing GI diagnoses. <h3>Methods</h3> A service evaluation was conducted of new patients attending our clinic, reporting diarrhoea after treatment for cancer. All patients attending the clinic completed a patient recorded outcome measure describing their symptoms and a Bristol Stool Chart describing stool type. They were investigated using a peer reviewed investigational and management algorithm. Patient characteristics, symptom incidence and severity were recorded prospectively. <h3>Results</h3> Over a 6 month period (July - Dec 2012), 207 patients were newly referred to the GIANTs. Of those, 104 (50%) reported diarrhoea (type 6 or 7 Bristol Stool Chart). In this group there were slightly more men (52%) than women (48%). Their median age was 62 years (range: 22–89). Primary tumour sites included urological cancer (34% - 82% of these prostate), gynaecological (22%), colorectal (20%), upper GI (10%), haematological (8%), and other (6%). 69% had undergone pelvic radiotherapy, 48% had been treated with surgery or received chemotherapy. 12% received pelvic radiotherapy alone, 6% surgery and 3% chemotherapy alone. Over a quarter (29%) received all 3 treatment modalities. Small intestinal bacterial overgrowth was found in 49%. Bile acid malabsorption was newly diagnosed in 33% of patients. Weak pelvic floor musculature was a contributing factor in 20%. 13% were diagnosed with new pancreatic insufficiency. Excess fibre intake (&gt;20g/day) was a contributory factor in 11% and Lansoprazole in up to 9% of patients. Other factors included: thyroid problems (9%), anal fissure (5%), rectal ulceration (5%), faecal loading (5%) and new onset Inflammatory Bowel Disease (3%). A colorectal polyp was found in 16% of patients, 1 patient had a new colorectal cancer and 2 had a GI stricture. 80% of patients had multiple causes for their diarrhoea. Most patients were discharged with a significant improvement in their symptoms with a median of 4 consultations (range 1–7) after systematic assessment and targeted management of the causes for their symptoms. <h3>Conclusion</h3> Diarrhoea after cancer treatment is frequent in the patient cohort seen in our clinic. Several GI causes contribute to diarrhoea simultaneously in most patients but the majority can be discharged after a small number of consultations with a significant improvement or full resolution of their symptom if a systematic investigational and treatment approach is adopted. <h3>Disclosure of Interest</h3> None Declared.
AB0772 Ocular manifestations of behcet’s disease
Authors: R.G. Goloeva, Z. Alekberova, V. Tankovskyi, I. Guseva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To study of ocular pathology in BD and association with clinical features, gender and the antigen HLA-B51. <h3>Methods</h3> 250 BD pts were evaluated in the Research Institute of Rheumatology RAMS from 1990 to 2010 years. BD was diagnosed according to criteria of International Study Group for Behcet's Disease (ISGBD). The test for HLA B51 was performed using microlymphocytotoxity method. <h3>Results</h3> Ocular involvement were revealed in 135 of patients: lesion anterior and posterior segments of the eye (punuveitis) had 53% of pts, of occlusive retinopathy - 29%, isolated retinal vasculitis - 30%, hypopyon - 12%. Manifestation of ocular pathology with of venous thrombosis of the retina was found in 3% of pts. In 8% of the pts eye involvement was the first symptom. The mean age at onset of uveitis was 25 years [21, 30], the eyes were involved in the process of the 3-d year disease [1, 6]. In 15 patients with decreased visual acuity in both eyes is less than 0.1 for the third year course of uveitis, 10 patients lost vision in one eye and a significant decrease in visual acuity second eye (less than 0.1) for 5 years course of uveitis [2,5, 6]. Three men were blind to the 3-d year of illness. The vast majority of patients with significant loss of visual function has been a late diagnosis and delayed treatment. Uveitis is diagnosed more often in male patients, the male-to-female ratio was 4,6:1. We found correlation of uveitis with male sex (r=0,27, p=0,00001), the antigen HLA-B51 (r=0,25, p=0, 0003) and a negative correlation with gastrointestinal lesions (r= -0,16, p=0,008). <h3>Conclusions</h3> Eye involvement in BD associated with male gender and HLA-B51 antigens. <h3>Disclosure of Interest</h3> None Declared
Case 15-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, William E. Harmon, Shane Meehan
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 14-year-old girl was admitted to the hospital because of biochemical features of advanced renal failure.The patient had been apparently well and active until two months earlier, when she began to experience fatigue after exercise, increasing lethargy, and occasional epistaxis. Four weeks before admission muscle cramps developed in the legs and often awakened her. Two weeks before entry a pediatrician found no abnormality except for slight proteinuria and a mixed bacterial flora in the urine. During the several days before admission her breathing became “labored.” On the day of admission laboratory studies were performed at another . . .
AN EFFECTIVE MHEALTH SERVICE TO REDUCE BLOOD PRESSURE WITHOUT ADDING MEDICATIONS THROUGH PERSONALIZED AUTOMATED LIFESTYLE INTERVENTIONS
Authors: Domenico Cianflone, Gaia Del Mauro, Tommaso Bordignon, Colombo Eros, Martina Fabi, Sara Costeri, Nicole A. Cristell, Ilaria Viscone
Journal: Journal of the American College of Cardiology (2016)
Medical profession at last speaks out over abortion
Authors: J. Roberts
Journal: BMJ (1995)

The US medical establishment remained silent throughout the decades of debate over abortion, but the anti-abortion uproar which accompanied the nomination of Dr. Henry Foster to succeed Dr. Jocelyn Elders as surgeon general of the US finally goaded major medical groups to take a stand. Dr. Foster reported that he had performed 39 abortions during his 38-year career as a gynecologist. Critics claim that he is lying and, despite the fact that he extols the virtues of abstinence in order to prevent adolescent pregnancy, abortion foes oppose his nomination. In response, the American Medical Association, the American College of Obstetricians and Gynecologists, and five other major medical groups stated that abortion is a legal medical procedure and should not be used as a reason to discredit a candidate for surgeon general. Nevertheless, it seems unlikely that Foster, an eminently qualified candidate, will see his nomination upheld by Congress.
461 INTEGRATING QUANTITIATIVE SERUM HBSAG LEVELS INTO RISK SCORES FOR PREDICTING HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B PATIENTS
Authors: C.-J. Chen, M.-H. Lee, H.-I. Yang, J. Liu, R. Batrla-Utermann, C.-L. Jen, U.H. Iloeje, J. Su, S.-N. Lu, S.-L. You, L.-Y. Wang
Journal: Journal of Hepatology (2012)
LEFT ATRIAL CONDUIT AND ACTIVE FUNCTION RELATES TO LEFT VENTRICULAR REMODELING AND REGIONAL FUNCTION: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Ravi K. Sharma, Mohammadali Habibi, Bharath Ambale Venkatesh, Luisa Ciuffo, Seo Young Hong, Masamichi Imai, Boaz D. Rosen, Antoinette Gomes, Susan Heckbert, Steven Shea, Robyn McClelland, Colin Wu, W. Hundley, David Bluemke, Joao Lima
Journal: Journal of the American College of Cardiology (2015)