tbuckley/cabot-search huggingface dataset:
Abstract #4352: The role of HOP tumor suppressor gene in head and neck cancer
Authors: Lee Fah Yap, Muhammad Mamduh Ahmad Zabidi, Soo Hwang Teo, Ian Paterson
Journal: Cancer Research (2009)

Oral squamous cell carcinoma (OSCC) and nasopharyngeal carcinoma (NPC) are two distinct types of head and neck cancer (HNC) with very different etiologies; OSCC is caused primarily by tobacco and alcohol and NPC is strongly associated with Epstein Bar virus infection. HNC is a major world health problem and both OSCC and NPC are particularly prevalent in Asian countries. The identification of genes whose expression are de-regulated in both OSCC and NPC would be a significant advance because these genes are likely to be of fundamental importance to the development and progression of HNC in general. Using Affymetrix microarrays, we have compared gene expression in OSCC and NPC with that of the corresponding normal controls. The homeodomain-only protein, HOP, was found to be down-regulated in both tumor types and the results were validated in OSCC/NPC cell lines and tissue samples by RT-PCR and quantitative real-time PCR, respectively. The HOP gene contains two promoters that encode the identical protein via the expression of two transcripts, termed HOP\#945; and HOP\#946;. Treatment of OSCC cells with the DNA demethylating agent, Zebularine, together with the histone deacetylase inhibitor, TSA, restored HOP expression and pyrosequencing analysis of bisulphite treated DNA showed evidence of methylation within the CpG island of the HOP\#946; promoter, suggesting that HOP expression is down-regulated in part by epigenetic mechanisms. In cells where HOP was more readily detected, DNA sequence analysis showed that the coding sequence of HOP was wild type, indicating that HOP is unlikely to be inactivated by mutation. Transfection of HOP into an OSCC cell line resulted in a reduction in colony forming ability and those cells that stably expressed HOP grew significantly slower than vector-transfected controls and were more susceptible to UV-induced apoptosis. In summary, our data demonstrate that HOP functions as a tumor suppressor in OSCC and NPC and indicate that loss of HOP expression may be central to the pathogenesis of HNC by promoting cell proliferation and inhibiting mitochondrial-mediated apoptosis.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4352.
Outcomes of Adult Philadelphia Positive Acute Lymphoblastic Leukemia Patients Treated with Pediatric Multi-Agent Chemotherapy and Imatinib and the Impact of Residual Disease Monitoring on Survival
Authors: Solaf Sami Kanfar, Steven M. Chan, Vikas Gupta, Aaron D. Schimmer, Andre C. Schuh, Hassan Sibai, Karen W.L. Yee, Mark D. Minden
Journal: Blood (2016)
Image Gallery: Cutaneous lesions in the external auditory canal causing hearing loss
Authors: K. Kieselova, F. Santiago, M. Henrique, F. Cunha
Journal: British Journal of Dermatology (2017)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 51‐year‐old previously healthy man was observed for a 3‐month history of rapidly growing firm nodules in both external auditory canals (EACs) causing hypoacusis (a). Skin biopsy with Congo red stain identified amyloid deposition (b). Subsequent study revealed anaemia, renal insufficiency, monoclonal band of kappa light chains in serum and urine and multiple osteolytic lesions of the ribs. Bone marrow biopsy showed plasmacytic infiltration. In this case, the amyloid light‐chain amyloidosis was the first manifestation of multiple myeloma. Its presentation as multiple exophytic nodules occluding the EAC is unique, rather than the diffuse skin thickening of the EAC reported in previous cases.1,2
Autologous dendritic cell vaccination (DCVAC/OvCa) added to standard of care therapy in three open-label randomized phase 2 studies in women with advanced stage ovarian cancer (OC).
Authors: Lukas Rob, Jirina Bartunkova, David Cibula, Pawel Knapp, Zuzana Namestkova, Radek Spisek, Jan Waclav, Peter Mallmann
Journal: Journal of Clinical Oncology (2014)

TPS3134 Background: OC is the 5th most common type of cancer in women and the 4thmost common cause of cancer death in women. Immunotherapy, for induction of tumor cell specific immune responses destroying tumor cells, has emerged as a promising treatment modality in solid malignant tumors. Studies have shown that chemotherapy can be combined with vaccine without blunting the response to the vaccine. Methods: The approach tested in the reported trials is a patient specific active cellular immunotherapy using autologous dendritic cells differentiated from peripheral blood monocytes and presenting tumor antigens derived from killed OC cell lines (SK-OV-3, OV-90). A phase 1 trial of DCVAC/OvCa (EudraCT 2010-021462-30) was the basis for the phase 2 program. This includes 3 protocols designed for patients with 1stline treatment, relapsed Pt-sensitive and relapsed Pt-resistant advanced stage OC. Immunotherapy is added to standard chemotherapy. SOV01 (90 pts; EudraCT 2013-001322-26): A randomized, open-label, three-arm, multi-center Phase II clinical trial evaluating effect of addition of DCVAC/OvCa to first line standard chemotherapy (carboplatin and paclitaxel) in women with newly diagnosed epithelial ovarian carcinoma. SOV02 (60 pts; EudraCT 2013-001323-38): A randomized, open-label, parallel group, multi-center Phase II clinical trial evaluating effect of addition of DCVAC/OvCa to standard chemotherapy (carboplatin and gemcitabine) in women with relapsed platinum sensitive epithelial ovarian carcinoma. SOV03 (60 pts; EudraCT 2013-001325-24): A randomized, open-label, parallel group, multi-center Phase II clinical trial evaluating effect of addition of DCVAC/OvCa to standard chemotherapy in women with relapsed platinum resistant epithelial ovarian carcinoma. The first patient in the phase 2 program was enrolled November 5, 2013, and all 3 trials are now recruiting patients. As of February 3, 10 patients had been screened and 7 had been randomized. Clinical trial information: EudraCT 2013-001322-26.
Cutting-edge Efforts in Surgical Patient Safety
Authors: Thomas K. Varghese, Amir A. Ghaferi
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension
Authors: Cheol Hwangbo, Heon-Woo Lee, Hyeseon Kang, Hyekyung Ju, David S. Wiley, Irinna Papangeli, Jinah Han, Jun-Dae Kim, William P. Dunworth, Xiaoyue Hu, Seyoung Lee, Omar El-Hely, Avraham Sofer, Boryeong Pak, Laura Peterson, Suzy Comhair, Eun Mi Hwang, Jae-Yong Park, Jean-Leon Thomas, Victoria L. Bautch, Serpil C. Erzurum, Hyung J. Chun, Suk-Won Jin
Journal: Circulation (2017)

Bone morphogenetic protein (BMP) signaling has multiple roles in the development and function of the blood vessels. In humans, mutations in BMP receptor type 2 (BMPR2), a key component of BMP signaling, have been identified in the majority of patients with familial pulmonary arterial hypertension (PAH). However, only a small subset of individuals with BMPR2 mutation develops PAH, suggesting that additional modifiers of BMPR2 function play an important role in the onset and progression of PAH.We used a combination of studies in zebrafish embryos and genetically engineered mice lacking endothelial expression of Vegfr3 to determine the interaction between vascular endothelial growth factor receptor 3 (VEGFR3) and BMPR2. Additional in vitro studies were performed by using human endothelial cells, including primary lung endothelial cells from subjects with PAH.Attenuation of Vegfr3 in zebrafish embryos abrogated Bmp2b-induced ectopic angiogenesis. Endothelial cells with disrupted VEGFR3 expression failed to respond to exogenous BMP stimulation. Mechanistically, VEGFR3 is physically associated with BMPR2 and facilitates ligand-induced endocytosis of BMPR2 to promote phosphorylation of SMADs and transcription of ID genes. Conditional, endothelial-specific deletion of Vegfr3 in mice resulted in impaired BMP signaling responses, and significantly worsened hypoxia-induced pulmonary hypertension. Consistent with these data, we found significant decrease in VEGFR3 expression in pulmonary arterial endothelial cells from human PAH subjects, and reconstitution of VEGFR3 expression in PAH pulmonary arterial endothelial cells restored BMP signaling responses.Our findings identify VEGFR3 as a key regulator of endothelial BMPR2 signaling and a potential determinant of PAH penetrance in humans.
Infections from seven clinical trials of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriasis
Authors: K.A. Papp, H. Bachelez, A. Blauvelt, K.L. Winthrop, R. Romiti, M. Ohtsuki, N. Acharya, D.K. Braun, L. Mallbris, F. Zhao, W. Xu, C.D. Walls, B. Strober
Journal: British Journal of Dermatology (2017)

Infections are associated with biological therapies in psoriasis.To summarize the incidence of infections in patients with moderate-to-severe psoriasis treated with ixekizumab, an anti-interleukin-17A monoclonal antibody.Infections are summarized from an integrated database of seven controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0-12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12-60; UNCOVER-1 and UNCOVER-2), and all patients exposed to ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported.Overall, 4209 patients were treated with ixekizumab (6480 PY). During induction (weeks 0-12), overall infection rates were higher in patients treated with ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer-term exposure. For all patients treated with ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation.Overall, infections occurred in a higher percentage of patients treated with ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups.
EPIDEMIOLOGY OF SPORTS INJURIES DURING DUTCH PHYSICAL EDUCATION TEACHER EDUCATION OVER THE PERIOD 2000–2014
Authors: Maarten Barendrecht, Carl Barten, Evert Verhagen, Bouwien Smits-Engelsman
Journal: British Journal of Sports Medicine (2017)

Background Injury risk is high during PE teacher education (PETE) and varies between curriculum years, settings and sex. Prospective studies covering the full 4-year period of PETE training are needed to identify risk factors. Objective To identify the contribution of specific sports, settings (intra- versus extracurricular), curriculum years and sex to the nature and distribution of sports injuries in PE students. Design Prospective cohort study. Setting A Dutch polytechnic for PETE. Patients (or Participants) All 2,903 PE students (male n=1,951, female n=954), who were enrolled between 2000 and 2014. Assessment of Risk Factors Nature and distribution of sports injuries were summarized for the following categories: sex, sports, setting, and curriculum year. Main Outcome Measurements All new musculoskeletal complaints related to sports participation, for which medical advice was sought by any of the PETE students. Results A total of 2,326 new injuries were reported by 1,332 students. For both sexes injuries to the ankle (n=494, 21.2%), knee (n=474, 20.4%), lower leg (n=249, 10.7%), shoulder (n=209, 9.0%) and back (n=183, 7.9%) were most frequently reported. The percentage of knee and back injuries increased after the first year, whereas the percentage of lower leg injuries decreased by 57%. Most intracurricular injuries were sustained during gymnastics (20.7%), team sports (20.4%) and track and field athletics (12.0%). Soccer (40.0%; female 19.8%, male, 51.0%) and other team sports (22.2%; female 35.4%, male 15.1%) accounted for most extracurricular injuries. Most ankle injuries (89.7% acute) were sustained during team sports (51.9%) and gymnastics (16.4%). Lower leg injuries (84.3% overuse), and knee, shoulder and back, injuries were sustained during more diverse sports activities. Conclusions Differential injury distributions for specific injuries between curriculum years, setting and sports need to be taken into consideration in further research on injury risk and preventive measures in PETE.
Erratum: The classification of glomerulonephritis in systemic lupus ereythematosus revisited (Kidney International (2004) 65 (521-530))
Authors: J. J. Weening, V. D. D'Agati, M. M. Schwartz, S. V. Seshan, C. E. Alpers, G. B. Appel, J. E. Balow, J. A. Bruijn, T. Cook, F. Ferrario, A. B. Fogo, E. M. Ginzler, L. Hebert, G. Hill, P. Hill, J. C. Jennette, N. C. Kong, P. Lesavre, M. Lockshin, L. M. Looi, H. Makino, L. A. Moura, M. Nagata
Journal: Kidney International (2004)
Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation
Authors: Fayhan J. Alroqi, Louis-Marie Charbonnier, Safa Baris, Ayca Kiykim, Janet Chou, Craig D. Platt, Abdulrahman Algassim, Sevgi Keles, Bandar K. Al Saud, Fowzan S. Alkuraya, Michael Jordan, Raif S. Geha, Talal A. Chatila
Journal: Journal of Allergy and Clinical Immunology (2017)
Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms
Authors: Ajay Malhotra, Xiao Wu, Howard P. Forman, Holly K. Grossetta Nardini, Charles C. Matouk, Dheeraj Gandhi, Christopher Moore, Pina Sanelli
Journal: Annals of Internal Medicine (2017)

Background: Small unruptured intracranial aneurysms (UIAs) are increasingly diagnosed. Management depends on growth and rupture risks, which may vary by aneurysm size. Purpose: To summarize evidence about the growth and rupture risk of UIAs 7 mm and smaller and to explore differences in growth and rupture risks of very small (≤3 mm) and small (≤5 mm) aneurysms. Data Sources: MEDLINE, EMBASE, Scopus, and the Cochrane Library from inception to 2017 (with no language restrictions). Study Selection: Published case series and observational studies that reported natural history data on UIAs 7 mm and smaller. Data Extraction: 2 reviewers abstracted study information, evaluated study quality, and graded strength of evidence. Data Synthesis: Of 26 studies, 5, 10, and 8 described the growth rate of aneurysms 3 mm and smaller, 5 mm and smaller, and 7 mm and smaller, respectively, whereas rupture rates were reported in 7, 11, and 13 studies for aneurysms 3 mm and smaller, 5 mm and smaller, and 7 mm and smaller, respectively. The annualized growth rate was less than 3% in all but 1 study for all 3 size categories. The annualized rupture rate was 0%, less than 0.5%, and less than 1% for the 3 size categories, respectively. Strength of evidence was very low quality for growth rates and low quality for rupture rates. Limitation: Heterogeneous definitions of growth; heterogeneous and selective treatment and follow-up methods, particularly in high-risk patients. Conclusion: Poor-quality evidence suggests that small UIAs have low growth and rupture rates and very small UIAs have little or no risk for rupture. Primary Funding Source: None.
Early-stage breast cancer patients reporting difficulty sleeping, mood issues, or pain are more likely to refuse adjuvant hormone therapy.
Authors: Christian A. Thomas
Journal: Journal of Clinical Oncology (2017)

e12065 Background: Adjuvant hormone therapy is a crucial part of the treatment for patients with early stage breast cancer and an important quality measure for programs such as QOPI and the oncology care model (OCM). However, it is not known which factors influence some patients with early stage breast cancer to decline adjuvant hormone therapy. We hypothesized that specific self-reported symptoms might impact a patient’s decision to accept or decline adjuvant hormone therapy. Methods: Patients with stage 0 or I breast cancer were identified by chart review from 2011-2016 and de-identified. On the day patients received a recommendation for adjuvant treatment the following patient reported outcome measures (PROs) were analyzed: difficulty sleeping (DS), fatigue (F), mood (M such as anxiety and depression), and pain (P) on a 0-4 symptom scale based on CTCAE v. 4. PROs were then linked with a patient’s decision to accept or decline adjuvant therapy. Results: A total of 287 patients with stage 0 (n = 80) or stage I (n = 207) breast cancer were identified. 38 stage O and 103 stage I patients had evaluable PROs on the same day a recommendation for adjuvant hormone therapy was made. Overall 18/38 (47.4%) of stage 0 patients and 90 of 103 (87.4%) of stage I patients accepted adjuvant treatment. Stage 0 patients declining adjuvant therapy reported any grade of PROs: DS (40%, n = 8), F (35%, n = 7), M (35%, n = 7), P (20%, n = 4). Stage 0 patients accepting treatment reported: DS (22%, n = 4), F (44%, n = 8), M (6%, n = 1), P (20%, n = 4). Stage I patients who declined treatment reported: DS (54%, n = 7), F (46%, n = 6), M (38%, n = 5), P (62%, n = 8). Stage I patients accepting treatment reported: DS (41%, n = 37), F (49%, n = 44), M (31%, n = 28), P (36%, n = 32). Conclusions: Early stage breast cancer patients declining adjuvant hormone therapy are more likely to self report symptoms such as difficulty sleeping, mood disturbances (anxiety, depression), and pain than those accepting treatment.
What's in a name?
Authors: H H Langston
Journal: BMJ (1988)

Aortic mural thrombus (AMT) is an uncommon cause of arterial thromboembolism. It is very rare in patients without significant cardiovascular risk factors. Many aetiologies can cause AMT, but there are no clear guidelines for the evaluation and treatment. We present the case of a 43-year-old woman without arteriosclerotic disease who was admitted to the hospital with peripheral embolisation from the mural thrombus in the distal arch of the aorta. Therapy with systemic anticoagulation resulted in complete resolution without necessitating any surgical or endovascular interventions. There were no reported recurrence or complications of the intra-aortic thrombus within 1-year surveillance imaging study.
Complete p53 multi-exon sequencing by gene chip complements use of p53 immunohistochemistry for prediction of clinical outcome in invasive bladder cancer
Authors: Ben George, Ram H. Datar, Lin Wu, Stephen J. Beil, Nancy Patten, Jie Cai, Susan Groshen, Richard J. Cote
Journal: Cancer Research (2004)

1791  Semaphorin 3B (SEMA3B) is a secreted member of the semaphorin family that is characterized by the presence of a highly conserved semaphorin domain. These proteins have been implicated in axon guidance by sending repulsive cues to growing axons in species from flies to vertebrate. Recently, ourselves and others have described tumor suppressor activity of SEMA3B in non-small cell lung cancer (NSCLC) and ovarian cancer cells (Tomizawa et al, PNAS 98: 13954, 2001; Tse et al, Cancer Res. 62: 542, 2002). We have also shown the antagonistic relationship between VEGF165 and SEMA3B, which coincided with other semaphorin family members. We now investigate the signaling pathway(s) used by SEMA3B to inhibit cell growth or induce apoptosis in lung and breast cancer cells. Protein kinase B (PKB)/AKT promotes cell survival signals through the phosphoinositide 3-kinase (PI3K) pathway, leading to inactivation of a series of pro-apoptotic proteins. We found that transfection of various lung cancer cell lines with the plasmid encoding SEMA3B severely restricts proliferation and clonogenic potential of these cells. The conditioned medium derived from COS7 cells transiently expressing SEMA3B (exogenous SEMA3B) also inhibited lung cancer growth in vitro. Furthermore, we observed that exogenous treatment with SEMA3B inhibited or decreased AKT phosphorylation in serine 473 leading to decreased AKT activity. We also observed SEMA3B induced changes in phosphorylation of other proteins important in apoptotic pathways including BAD, GSK-3beta, FKHR, and PTEN. These results lead to the hypothesis that apoptotic effects of SEMA3B on tumor cells might be mediated in part via blockade of the AKT pathway.