tbuckley/cabot-search huggingface dataset:
Abstract P6-10-02: Not presented
Authors: SL McDonnell, CA Baggerly, CB French, LL Baggerly, CF Garland, ED Gorham, JM Lappe
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: McDonnell SL, Baggerly CA, French CB, Baggerly LL, Garland CF, Gorham ED, Lappe JM. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-10-02.
Investigating vitamin B12 deficiency
Authors: Nithya Sukumar, Ponnusamy Saravanan
Journal: BMJ (2019)

### What you need to know

A 44 year old woman attends her general practitioner with a two year history of lethargy, which has resulted in her being unable to continue her job as a primary school teacher. She had a history of anaemia a few years ago and was not taking any regular medication, except for the combined contraceptive pill. Her mother has hypothyroidism for which she takes levothyroxine; there is no other family history of note. Physical examination was unremarkable. Recent blood tests showed haemoglobin 110 g/L (reference range 115-160) and mean corpuscular volume 102 fL (range 80-100). To further investigate the cause of her macrocytic anaemia, blood tests for vitamin B12 and folate were requested, which showed vitamin B12 138 pmol/L (reference range 148-600 (to convert from pmol/L to ng/L, multiply by 1.355)) and folate 40.5 nmol/L (4.5-45 (to convert to μg/L, divide by 2.27)).

The prevalence of vitamin B12 (B12) deficiency is approximately 6-12% in adults under 60 years old and around 17% in all adults with macrocytic anaemia.123 However, elderly people, pregnant women, and vegans are more susceptible to B12 deficiency, so have a higher index of suspicion in these populations in the presence of suggestive symptoms and signs (box 1). Some …
Assessment of small bowel mucosal healing by video capsule endoscopy for the prediction of short-term and long-term risk of Crohn's disease flare: a prospective cohort study
Authors: Shomron Ben-Horin, Adi Lahat, Marianne M Amitai, Eyal Klang, Doron Yablecovitch, Sandra Neuman, Nina Levhar, Limor Selinger, Noa Rozendorn, Dan Turner, Yehuda Chowers, Shmuel Odes, Doron Schwartz, Henit Yanai, Iris Dotan, Tzipi Braun, Yael Haberman, Uri Kopylov, Rami Eliakim
Journal: The Lancet. Gastroenterology & hepatology (2019)
Abstract P6-18-13: Identification of optimal combination therapy partners for PI3K/Akt/mTOR pathway inhibitor in triple negative breast cancer
Authors: M Shariati, N Paez-Arango, CA Bristow, KW Evans, MD Peoples, A Carugo, TP Heffernan, F Meric-Bernstam
Journal: Cancer Research (2019)

Abstract Triple-negative breast cancer (TNBC) is among the most aggressive subtypes, accounts for 10-15% of all breast cancer cases and is characterized by a lack of hormone receptors with a low overall survival rate. Due to the heterogeneity nature of this disease, the absence of validated molecular targets makes it unresponsive to conventional therapies. PI3K/Akt/mTOR pathway is aberrantly activated in TNBC, but single agent therapy is commonly subject to resistance. The goal of this study is to identify the genes that can be targeted to enhance the efficacy of mTOR inhibitor TAK228, an agent that is being investigated as a treatment for advanced solid tumors, in TNBC with PI3K pathway activation. We utilized an in vivo pooled barcoded shRNA library screening to determine the genes that have the potential to be used as TAK228 synthetic lethal partners. Using deep sequencing analysis of the shRNA profiles, we identified several genes whose loss of function conferred synthetic lethality in the presence of TAK228. We found that targeting the candidate genes (WEE1, BMX and MAPK15) with their inhibitors (AZD1775, Ibrutinib and Sunitinib) did not significantly affect the viability, however combination treatment of these agents with TAK228 induced a robust growth inhibition and demonstrated a significant synergy in MDA-MB-468 cell lines. Investigating the activation of relevant survival signaling pathways will further elucidate the mechanism of synthetic lethal interaction. These observations provide a promising rational strategy for the treatment of TNBC with PI3K pathway aberration. Citation Format: Shariati M, Paez-Arango N, Bristow CA, Evans KW, Peoples MD, Carugo A, Heffernan TP, Meric-Bernstam F. Identification of optimal combination therapy partners for PI3K/Akt/mTOR pathway inhibitor in triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-13.
Guidelines for Secondary Solid Cancers Among HSCT Recipients—In Reply
Authors: André Tichelli, Gérard Socié, Nina Salooja
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
Challenges and benefits of being an ethnic minority student
Authors: Heval Mohamed Kelli
Journal: BMJ (2012)

My first day of medical school reminded me of the day I arrived as an immigrant to the US. Being one of the first people of my community to enter medical school carried tremendous pressure. Ethnic minority students face several challenges that hinder them from pursuing higher education, such as lack of mentorships and organised educational support, cultural differences, and financial burden. Despite the obstacles, foreign born students provided with the necessary resources can outperform native born students in the academic arena.1

Medical school demands a strong mental …
Plasma Cell Leukemia (PCL): Clinical Characteristics, Outcomes, and the Impact of Circulating Plasma Cells (CPC) Percentage — A Single Center Experience
Authors: Noa G. Holtzman, Olga Goloubeva, Zeba Singh, Sameer Sawhney, Ying Zou, Jean Yared, Nancy M. Hardy, Aaron P. Rapoport, Mehmet H. Kocoglu, Ashraf Z. Badros
Journal: Blood (2017)
Photosensitive Hydrogel Creates Favorable Biologic Niches to Promote Spinal Cord Injury Repair
Authors: Zhengwei Cai, Yibo Gan, Chunyan Bao, Wanjiang Wu, Xuebin Wang, Zetong Zhang, Qiang Zhou, Qiuning Lin, Yi Yang, Linyong Zhu
Journal: Advanced Healthcare Materials (2019)

Photochemistry is considered to be a promising strategy for hydrogels to mimic the complex and dynamic properties of natural extracellular matrix. However, it is seldom applied in 3D tissue engineering and regenerative medicine due to the attenuation of light. In this study, phenyl azide photchemistry and optical fiber technology are first used to localize adhesive protein on the inner surface of the nerve guidance conduit in a 3D hydrogel scaffold. In vitro coculture assay of neural stem cells (NSCs) shows that photoimmobilization of collagen significantly improves the adhesion and survival of NSCs in the conduit, and exhibits synergistic effect with the sustainable release of growth factor. After implantation in transected spinal cord, the optimized hydrogel scaffold is found to improve the locomotion recovery of rats 12 weeks after spinal cord injury (SCI). Histological analysis suggests that the designed hydrogel scaffold provides a favorable biological niche for neuronal regeneration, thus producing directional neuron tissue and promoting the repair of SCI. This study demonstrates a promising hydrogel scaffold for SCI repair and provides the first understanding of the photoimmobilization of adhesive protein in a 3D hydrogel conduit concerning its functions on spinal cord tissue restoration.
Proteomic analysis of meningiomas reveals clinically distinct molecular patterns
Authors: Michail-Dimitrios Papaioannou, Ugljesa Djuric, Jennifer Kao, Shirin Karimi, Gelareh Zadeh, Kenneth Aldape, Phedias Diamandis
Journal: Neuro-Oncology (2019)

Abstract Background Meningiomas represent one of the most common brain tumors and exhibit a clinically heterogeneous behavior, sometimes difficult to predict with classic histopathologic features. While emerging molecular profiling efforts have linked specific genomic drivers to distinct clinical patterns, the proteomic landscape of meningiomas remains largely unexplored. Methods We utilize liquid chromatography tandem mass spectrometry with an Orbitrap mass analyzer to quantify global protein abundances of a clinically well-annotated formalin-fixed paraffin embedded (FFPE) cohort (n = 61) of meningiomas spanning all World Health Organization (WHO) grades and various degrees of clinical aggressiveness. Results In total, we quantify 3042 unique proteins comparing patterns across different clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic (n = 106 proteins, Welch’s t-test, P &lt; 0.01) and pathway-level (eg, Notch and PI3K/AKT/mTOR) differences between convexity and skull base meningiomas. Supervised comparative analyses of different pathological grades revealed distinct patterns between benign (grade I) and atypical/malignant (grades II‒III) meningiomas with specific oncogenes enriched in higher grade lesions. Independent of WHO grade, clinically aggressive meningiomas that rapidly recurred (&lt;3 y) had distinctive protein patterns converging on mRNA processing and impaired activation of the matrisome complex. Larger sized meningiomas (&gt;3 cm maximum tumor diameter) and those with previous radiation exposure revealed perturbed pro-proliferative (eg, epidermal growth factor receptor) and metabolic as well as inflammatory response pathways (mitochondrial activity, interferon), respectively. Conclusions Our proteomic study demonstrates that meningiomas of different grades and clinical parameters present distinct proteomic profiles. These proteomic variations offer potential future utility in helping better predict patient outcome and in nominating novel therapeutic targets for personalized care.
Let-7 miRNA and CDK4 siRNA co-encapsulated in Herceptin-conjugated liposome for breast cancer stem cells
Authors: Jeong Hyun Shin, Dae Hwan Shin, Jin Seok Kim
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Recently, breast cancer stem cells (BCSCs) have rapidly emerged as a novel target for the therapy of breast cancer as they play critical roles in tumor growth, maintenance, metastasis, and recurrence. Let-7 miRNA is known to be downregulated in a variety of cancers, especially BCSCs, whereas CDK4 being overexpressed in human epidermal growth factor receptor 2 (HER-2) overexpressing tumor cells. In this study, let-7 miRNA and CDK4-specific siRNA were chosen as therapeutic agents and co-encapsulated in Herceptin-conjugated cationic liposomes for breast cancer therapy. Particle size, zeta potential, and encapsulation efficacy of mi/siRNA-loaded PEGylated liposome conjugated with Herceptin (Her-PEG-Lipo-mi/siRNA) were 176 nm, 28.1 mV, and 99.7% ± 0.1%, respectively. Enhanced cellular uptake (86%) was observed by fluorescence microscopy when SK-BR-3 cells were treated with Her-PEG-Lipo-mi/siRNA. Also, the increased amount of let-7a mRNA and decreased amount of cellular CDK4 mRNA were observed by qRT-PCR when SK-BR-3 cells were treated with Her-PEG-Lipo-mi/siRNA, which was even more so when SK-BR-3 stem cells were used (197 vs 768 times increase for let-7a, 62% vs 68% decrease for CDK4). Growth inhibition (65%) and migration arrest (0.5%) of the cells were achieved by the treatment of the cells with Her-PEG-Lipo-mi/siRNA, but not with mi/siRNA complex or other formulations. In conclusion, an efficient liposomal delivery system for the combination of miRNA and siRNA to target the BCSCs was developed and could be used as an efficacious therapeutic modality for breast cancer.
Abstract P224: Higher Fruit and Vegetable Intake Was Associated With Lower Total and Cause-Specific Mortality in a Nonlinear Dose-Response Manner
Authors: Dong D Wang, Shilpa N Bhupathiraju, Yanping Li, Bernard A Rosner, Qi Sun, Eric B Rimm, JoAnn E Manson, Walter C Willett, Frank B Hu
Journal: Circulation (2018)

Introduction: The strength and dose-response relationship between fruit and vegetable intake and mortality are still subjects of debate. Hypothesis: We hypothesized that higher fruit and vegetable intake was associated with lower total and cause-specific mortality in a nonlinear dose-response manner. Methods: We followed 66,719 women from the Nurses’ Health Study (1984-2012) and 42,016 men from the Health Professionals Follow-up Study (1986-2012) who were free from cardiovascular disease (CVD), cancer and diabetes at baseline. Diet was assessed using food frequency questionnaires at baseline and updated every 2 to 4 years. Results: Our study documented 28,333 deaths during follow-up. The 3rd quintile of fruit and vegetable intake was associated with the lowest hazard ratio (HR) of total mortality (HR, 0.87, 95% CI, 0.83-0.90, P nonlinear &lt;0.001) compared to the 1st quintile. The nonlinear dose-response relationship plateaued at about 5 servings/day (svg/d), but above that level, higher intake was not associated with additional risk reduction. We found similar nonlinear associations for CVD, cancer and respiratory disease mortality. Compared to fruit and vegetable intake &lt;1.5 svg/d, the intake level ≥5 svg/d was associated with HRs (95% CI) of 0.84 (0.75-0.93), 0.82 (0.72-0.93) and 0.55 (0.44-0.67) for cancer, CVD and respiratory disease mortality, respectively. Among individual fruits and vegetables, the associations of intakes with mortality were heterogeneous. Higher intakes of most fruit and vegetable subgroups were associated with lower total mortality, whereas higher intake of starchy vegetable such as peas and corn was not associated with total mortality. Conclusions: Higher fruit and vegetable intake was associated with lower mortality; the lowest mortality was observed among those who consumed 5 servings of fruit and vegetables per day (2 servings of fruit and 3 servings of vegetables daily). Our findings also suggest the presence of heterogeneity in the health benefits of individual fruits and vegetables.
Abstract SY15-01: Using comparative oncogenomics to guide personalized cancer medicine
Authors: Ronald A. DePinho
Journal: Cancer Research (2010)

Abstract We exploited mouse models of cancer to identify prognosis determinants for guiding the management of early stage cancer such as prostate cancer. In the case of prostate cancer, effective management has beenchallenged by an elemental understanding of the genetic elements governingdisease progression. We hypothesized that pathways constraining invasive andmetastatic progression would be activated in indolent Pten null mouse prostatecancers and that deactivation of such progression checkpoints would occur upon disease progression in human prostate cancer. Using comparative transcriptomicand pathway analysis, we identifed and biochemically/genetically validated a TGFβ progression block which upon neutralization generates a lethal metastaticphentoype. This use of this metastatic mouse prostate cancer model, then enabled identification of a signature which, upon intersection with human data, can dichotomize men into high and low risk groups for progression. Citation Format: Ronald A. DePinho. Using comparative oncogenomics to guide personalized cancer medicine [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY15-01
Royal College of Surgeons warns against “mavericks” in new innovation guideline
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Surgeons should refrain from using new procedures and techniques if they lack the training and supervision to ensure patients’ safety, the Royal College of Surgeons has warned in new guidance on the best practice for using new techniques.1

The guidance, which comes after the death of a patient who had multiple organ failure after robot-assisted heart valve surgery,2 outlines the principles all surgeons …
Prognostic Value of Residual Disease after Neoadjuvant Therapy in HER2-Positive Breast Cancer Evaluated by Residual Cancer Burden, Neoadjuvant Response Index, and Neo-Bioscore
Authors: Tessa G. Steenbruggen, Maartje van Seijen, Liselore M. Janssen, Mette S. van Ramshorst, Erik van Werkhoven, Marie-Jeanne T.D.F. Vrancken Peeters, Jelle Wesseling, Esther H. Lips, Gabe S. Sonke
Journal: Clinical Cancer Research (2019)

In breast cancer, pathologic complete response (pCR) to neoadjuvant systemic therapy (NST) is associated with favorable long-term outcome. Trastuzumab emtansine as additional adjuvant therapy improves recurrence-free survival of patients with HER2-positive breast cancer without pCR, but it is uncertain whether all patients without pCR need additional therapy. We evaluated the prognostic value of residual disease after trastuzumab-based NST in patients with HER2-positive breast cancer using Residual Cancer Burden (RCB), Neoadjuvant Response Index (NRI), and Neo-Bioscore.We included patients with stage II or III HER2-positive breast cancer treated with trastuzumab-based NST and surgery at The Netherlands Cancer Institute between 2004 and 2016. RCB, NRI, and Neo-Bioscore were determined. Primary endpoint was 5-year recurrence-free interval (RFI). A 3% difference compared with the pCR group was considered acceptable as noninferiority margin on the 5-year RFI estimate, based on a proportional hazards model, and its lower 95% confidence boundary.A total of 283 women were included. Median follow-up was 67 months (interquartile range 44-100). A total of 157 patients (56%) with pCR (breast and axilla) had a 5-year RFI of 92% (95% CI, 88-97); patients without pCR had a 5-year RFI of 80% (95% CI, 72-88). Patients with an RCB = 1 (N = 40, 15%), an NRI score between 0.75 and 0.99 (N = 30, 11%), or a Neo-Bioscore of 0 to 1 (without pCR; N = 28, 11%) have a 5-year RFI that falls within a predefined noninferiority margin of 3% compared with patients with pCR.The RCB, NRI, and Neo-Bioscore can identify patients with HER2-positive breast cancer with minimal residual disease (i.e., RCB = 1, NRI ≥ 0.75, or Neo-Bioscore = 0-1) after NST who have similar 5-year RFI compared with patients with pCR.
Abstract LB-247: A multidisciplinary phase II study of AZD2171 (cediranib), an oral pan-VEGF receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma
Authors: Tracy T Batchelor, Gregory Sorensen, Emmanuelle di Tomaso, Dan G Duda, Wei-Ting Zhang, Marek Ancukiewicz, Johanna Lahdenranta, David Louis, Scott Plotkin, Percy Ivy, Jay S Loeffler, Patrick Wen, Rakesh K Jain
Journal: Cancer Research (2008)

Abstract Targeted agents are promising new therapeutics that have entered clinical trials for glioblastoma. AZD2171 (cediranib) is a potent, oral pan-VEGF receptor tyrosine kinase inhibitor with a half-life of 20 hours compatible with once-daily dosing. A primary target of AZD2171, VEGFR2, is expressed on glioblastoma endothelium. We have demonstrated normalization of tumor vessels in recurrent glioblastoma patients administered AZD2171 on a daily basis. Normalization has rapid onset, is reversible, and is associated with alleviation of brain edema (Batchelor TT, et al. Cancer Cell 2007;11:83-95). In this Phase II study of 31 recurrent glioblastoma subjects we now report clinical outcomes, including the proportion of patients alive and progression-free at 6 months (APF6) as the primary endpoint. Secondary endpoints include radiographic response proportion; progression-free survival; and overall survival and toxicity. At this time we are presenting radiographic response data, APF6, PFS, and OS on 31 patients. Thirty patients have experienced disease progression and one patient remains in follow-up without progression. The primary and secondary endpoints are tabulated below: Radiographic Responses Partial Response (more than 50% decrease in volume) in 16/30 (56%) APF6 [95% CI] 25.8% [14.7%, 46.9%] PFS [95% CI] 117 days [88, 145] OS [95% CI] 221 days [172, 285] Only one of the first 16 patients was removed from the study due to toxicity (fatigue). Dose limiting toxicities were observed in 9/16 patients with hypertension; fatigue and diarrhea were encountered most often. There have been no intracerebral hemorrhages. AZD2171 alleviated brain edema, a major cause of morbidity in glioblastoma patients, and had a steroid-sparing effect in many of the patients enrolled. Blood biomarkers were serially assessed and it was observed that plasma VEGF, PlGF, and SDF1α were increased after treatment. Plasma PlGF and VEGF decreased upon cediranib discontinuation. Plasma bFGF and SDF1α and viable circulating endothelial cells increased when tumors escaped treatment with AZD2171. AZD2171 is a promising therapy for glioblastoma and an attractive therapeutic partner for chemotherapy or radiation.
Top US universities fail to make the global health grade, says report
Authors: Chris Thomas
Journal: BMJ (2013)

Many top US and Canadian universities have received poor marks in the first University Global Health Impact Report Card ,1 which was designed to help measure the influence that universities are having on global health.

The report was compiled by Universities Allied for Essential Medicines (UAEM)—a student led group that aims to ensure universities contribute to global health research and access to treatment worldwide. Universities are major drivers of innovation, with up to one in three new medicines originating in …
Use of a colonic stent to recover a biliary stent retained by malignant colonic obstruction
Authors: Toshio Kuwai, Yuki Sumida, Ryoichi Miura, Yuki Miyasako, Kazutaka Kuroki, Yuzuru Tamaru, Hiroshi Kohno
Journal: Endoscopy (2019)

A 95-year-old woman had a 10 mm × 6 cm fully covered biliary stent implanted at another hospital to treat lower common bile duct stenosis caused by biliary neoplasm. Six months later, the stent became dislodged and migrated into the small intestine. Another uncovered biliary stent was inserted to replace it. She was kept under observation because of performance status 4; however, nausea and vomiting continued, and small intestinal obstruction caused by the migrated stent was suspected. She was later referred to our department for recovery.