tbuckley/cabot-search huggingface dataset:
Abstract A66: Anticancer activity of selective TrkB inhibition in medulloblastoma cells
Authors: Amanda Thomaz, Kelly V. Pinheiro, Camila A. da Silva, Caroline B. de Farias, Rafael Roesler
Journal: Clinical Cancer Research (2018)

Abstract Medulloblastomas (MB) occur in the central nervous system and are the most common pediatric intracranial tumors. Despite the knowledge regarding the molecular biology of these tumors, patients still suffer long-term side effects in consequence of the current treatments. Several advances have collaborated to the identification of new therapeutic targets for cancer treatment, including the characterization of BDNF/TrkB signalling in cell fate. This pathway has been associated with increased proliferative capabilities, invasiveness, and chemotherapy resistance in many types of cancer. We have previously shown that the selective TrkB inhibitor, ANA-12, markedly reduced the viability and survival of MB cell lines. These findings provided a rationale to further investigations relating TrkB inhibition as a potential novel strategy for MB treatment. We investigated the effects of ANA-12 in apoptosis and the effects of combined treatment with cisplatin in MB cell viability. Human MB cell lines D283 and UW-228 were treated with increasing concentrations of ANA-12 (5, 20, or 30 μM) or BDNF (50 ng/ml) for 24 or 48 hours. Cells were also treated with different combinations of ANA-12 and cisplatin for 48 hours. Cell viability was assessed by trypan blue cell counting. Cell apoptosis was analyzed by flow cytometry to annexin-V and propidium iodide staining. Data represent at least three independent experiments performed in triplicates. Statistical analyses: two-way ANOVA followed by followed by Tukey for multiple comparisons. We found that ANA-12 leads to a dose- and time-dependent reduction of D283 and UW-228 MB cell viability. ANA-12 at 30 μM increased the population of apoptotic cells in both MB cell lines. In D283 29.9% and 61.9% of the cells were apoptotic after 24 and 48 hours of treatment, respectively. In UW-228 apoptosis rates were 49.1% after 24 hours and 80.7% after 48 hours. When used in combination, ANA-12 enhanced cisplatin cytotoxic effects in UW-228 cells. Cell viability in the presence of 5 μM of cisplatin alone was 37.48% (UW-228) and 49.8% (D283), but decreased with the combination of 20 μM of ANA-12, 18.4% (UW-228) and 23.4% (D283). Here we present the evidence that in human MB, ANA-12 decreases viability, induces apoptosis, and acts synergistically with cisplatin in suppressing MB cell viability. Citation Format: Amanda Thomaz, Kelly V. Pinheiro, Camila A. da Silva, Caroline B. de Farias, Rafael Roesler. Anticancer activity of selective TrkB inhibition in medulloblastoma cells [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A66.
Emergence of ceftazidime-avibactam-resistant Klebsiella pneumoniae during treatment, Finland, December 2018
Authors: Kati Räisänen, Irma Koivula, Heikki Ilmavirta, Santeri Puranen, Teemu Kallonen, Outi Lyytikäinen, Jari Jalava
Journal: Eurosurveillance (2019)

In December 2018, a ceftazidime-avibactam (CAZ-AVI)-resistant KPC-2-producing Klebsiella pneumoniae strain was isolated in Finland. CAZ-AVI resistance was observed 34 days after CAZ-AVI treatment in a trauma patient transferred from a hospital in Greece who had been colonised with blaKPC-2-producing K. pneumoniae ST39, and later developed a bloodstream infection. The CAZ-AVI-resistant strain contained a novel 15 amino acid insertion in the KPC-2 protein causing structural changes proximal to the KPC-2 active site.
Abstract P5-02-04: Not presented
Authors: D Sheth, F Pineda, G Karczmar, H Abe
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Sheth D, Pineda F, Karczmar G, Abe H. 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 P5-02-04.
Abstract P3-03-02: Redo sentinel lymph node biopsy for ipsilateral breast tumor recurrence after breast conserving surgery with negative sentinel nodes: A pooled analysis from a systematic review and two institutes
Authors: C-i Yoon, SJ Bae, JE Choi, CH Cha, SE Park, SG Ahn, J Jeong
Journal: Cancer Research (2019)

Abstract Background:Cases of redo sentinel lymph node biopsy (SLNB) are growing according to the increase of ipsilateral breast tumor recurrence (IBTR) after breast-conservative surgery (BCS). To evaluate a feasibility of redo SLNB in patients with IBTR after negative SLN, we conveyed a pooled analysis using data from a systematic review and two institutes. Materials and methods:A systematic search of PubMed was conducted to identify data of patient level from publications evaluating redo SLNB for cases with IBTR. Eligible patients who underwent BCS and were confirmed as negative axilla after SLNB were identified. An identification rate (IR) and a false-negative rate (FNR) were calculated. To identify FNR, we only included cases with back-up axillary node dissection (ALND) from retrieved data. Results:In a systematic review, a total of 197 peer-reviewed publications were retrieved, of which 19 papers included patients who met eligibility criteria. Data from 464 patients were collected. In two-institutes, 38 cases with same criteria were identified. A total of 502 patient's data were pooled. The IR of redo-SLNB was 71.7% (360/502) in pooled data. For the FNR, data from 147 patients with back-up ALND after SLNB was analyzed. The FNR and accuracy of redo-SLNB were 9.8% (5/51) and 97% (142/147). Conclusions:We found that the IR and the FNR of redo SLNB were 71.7% and 9.8%, respectively. Redo SLNB is reliable procedure for axillary staging in patients with IBTR after negative SLNB. Citation Format: Yoon C-i, Bae SJ, Choi JE, Cha CH, Park SE, Ahn SG, Jeong J. Redo sentinel lymph node biopsy for ipsilateral breast tumor recurrence after breast conserving surgery with negative sentinel nodes: A pooled analysis from a systematic review and two institutes [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 P3-03-02.
Abstract P2-06-17: A novel interaction of AURKA with MAPK pathway in breast cancer cells as a potential therapeutic target
Authors: S Gandhi, M Gil, T Khoury, K Takabe, I Puzanov, I Gelman, A D'Assoro, M Opyrchal
Journal: Cancer Research (2019)

Abstract Background: Aurora A (AURKA) is a mitotic kinase responsible for centrosome segregation and mitotic spindle formation. In normal cells, expression of AURKA is highly regulated and is predominantly restricted to G2/M phases of the cell cycle. Unlike healthy cells, cancer cells overexpress AURKA through all phases of the cell cycle resulting in the acquisition of alternate non-mitotic functions. Little is known about cellular functions regulated by AURKA and its interaction with other signaling molecules. Here, we report a novel interaction between AURKA and the mitogen-activated protein kinase (MAPK) pathway at the level of MEK1 in breast cancer cells. This interaction may serve as a novel target as well as demonstrate by an additive cytotoxic effect of AURKA- and MEK1/2-specific inhibitors against estrogen positive (ER+) and triple negative breast cancer (TNBC) cells. Results: We show that treatment of ER+ HER2- MCF-7, ER- HER2+ SKBR3 and ER- HER2- BT549 cells with AURKA specific inhibitors alisertib, MK8745 and Aurora A Inhibitor I resulted in over 2-fold increase in relative levels of poMEK1/2 and poERK1/2 compared to untreated controls. The activation of the MAPK pathway was rapid with changes seen within 5 min after treatment with AURKA inhibitors and was sustained for at least 48 hours. Treatment with the pan RAF inhibitor TAK-632 did not diminish alisertib-induced poERK and poMEK1/2. Alternatively, treatment with the MEK1/2 specific inhibitor PD0325901 completely abrogated alisertib-induced phosphorylation of MEK1/2 and ERK1/2. In situ proximity ligation and pull down assays demonstrated AURKA and MEK1/2 direct interaction. In vitro kinase assay showed direct phosphorylation of MEK1 by AURKA. Combined treatment of alisertib and PD0325901 in vitro revealed significant additive cytotoxic effect in MCF-7 and BT549 cells when compared to either agent used alone (p&amp;lt; 0.008 and p&amp;lt;0.011; p &amp;lt;0.04 and p&amp;lt;0.028) with early trend toward significance in survival in a BT549 xenograft breast cancer in vivo model. Conclusions: Our data shows a novel AURKA-MEK1 interaction in breast cancer cells. In depth in vivo analysis is ongoing. The results reveal a promising new strategy for the treatment TNBC patients using a combination of AURKA and MEK1/2 inhibitors. Citation Format: Gandhi S, Gil M, Khoury T, Takabe K, Puzanov I, Gelman I, D'Assoro A, Opyrchal M. A novel interaction of AURKA with MAPK pathway in breast cancer cells as a potential therapeutic target [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 P2-06-17.
Abstract P1-19-07: Real-world characteristics, treatment patterns, and overall survival in patients with metastatic breast cancer (mBC) and CNS metastases
Authors: A Alvarado-Miranda, P Cabrera-Galeana, WR Muñoz-Montaño, F Lara-Medina, E Bargallo-Rocha, O Arrieta-Rodriguez, M Perez, F Porras-Reyes, A Mohar-Betancourt, C Gamboa
Journal: Cancer Research (2019)

Abstract Background: CNS metastases are reported in about 10 to 15%. Knowledge about the management of these patients are limited because they are excluded from clinical trials due to its poor prognosis and morbidity. In these study, we aim to describe characteristics, treatment patterns, and overall survival (OS) of patients of mBC with CNS metastases at Instituto Nacional de Cancerología de Mexico (INCan) from january 2007 to december 2015. Methods: We include patients with histological diagnosis of mBC and tumoral activity in the CNS (at diagnosis or during de follow-up). mBC subtype was defined using HER2 and hormone receptor (HR) status by immunohistochemistry; systemic treatment, and mortality data were used to characterize mBC with CNS involment. Results: During the study period, we found 1272 patients diagnosed with metastatic disease, of whom 408 had CNS disease (novo/recurrence) the median follow up was 52 months. Table 1 describes the percentage of CNS metastases by subtype, clinical characteristics at diagnosis and median OS. Almost all patients (85.6%) were candidate to holocranial radiotherapy; after that, systemic treatment varied according to the subtype of mBC; 69.1% of TN received CT (26% based on platinum); 75.3% of HER2+ received systemic treatment, all included antiher2 therapy; luminal subtype, no one were treated with endocrine therapy. Table 1.- characteristics and Overall suvival by subtype of mBC all mBC 1272 n(%)her2 positive 339 (26.6) n (%)triple negative 298 (23.4) n(%)luminal 636 (50) n(%)CNS metastasis at dianosis44 (3.5)12 (3.5)13 (4.4)19 (2.9)CNS mets after prog to systemic tx205(16.1)63(18.6)50(16.7)92(14.5)CNS as first place of recurrence159(12.5)75(22.2)34(11.4)50(7.8)prevalence on CNS mets408(10.7)150(14.7)97(10.8)161(8.4)median age at diagnosis of CNS mets50(28-84)50(29-84)48(28-80)51(28-80)median OS after CNS mets (months)14.927.29.3316.3 Conclusions: HER2 positive breast cancer patients have the highest prevalence of CNS metastases, whereas luminal has the lowest. Patients with HER2+ and CNS metastases commonly receive treatment based on anti-HER2 therapy, maybe this target treatment contribute to the better survival achieved than patients with luminal or TN subtype. mBC with CNS metastases continues in the real world to be an unmet medical need. Citation Format: Alvarado-Miranda A, Cabrera-Galeana P, Muñoz-Montaño WR, Lara-Medina F, Bargallo-Rocha E, Arrieta-Rodriguez O, Perez M, Porras-Reyes F, Mohar-Betancourt A, Gamboa C. Real-world characteristics, treatment patterns, and overall survival in patients with metastatic breast cancer (mBC) and CNS metastases [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 P1-19-07.
Increased Gastric MIBG Activity as a Normal Variant
Authors: Xia Bai, Xuemei Wang, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2019)

Abstract Although increased MIBG activity in the colon is a well-described and well-known normal variant, elevated MIBG activity in the stomach is rarely seen. We describe increased 123 I-MIBG accumulation in the stomach in a 13-year-old girl who had recurrent metastatic neuroblastoma. The activity appeared to be a new MIBG-avid lesion on the planar images. However, the SPECT/CT images revealed that the activity was inside the gastric lumen without anatomical abnormality. On a follow-up 123 I-MIBG scan acquired 3 months later, the stomach no longer had elevated MIBG activity, while the other abnormal activity on prior study remained the same.
Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non–Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study
Authors: Daniel R. Gomez, Chad Tang, Jianjun Zhang, George R. Blumenschein, Mike Hernandez, J. Jack Lee, Rong Ye, David A. Palma, Alexander V. Louie, D. Ross Camidge, Robert C. Doebele, Ferdinandos Skoulidis, Laurie E. Gaspar, James W. Welsh, Don L. Gibbons, Jose A. Karam, Brian D. Kavanagh, Anne S. Tsao, Boris Sepesi, Stephen G. Swisher, John V. Heymach
Journal: Journal of Clinical Oncology (2019)

Our previously published findings reported that local consolidative therapy (LCT) with radiotherapy or surgery improved progression-free survival (PFS) and delayed new disease in patients with oligometastatic non-small-cell lung cancer (NSCLC) that did not progress after front-line systemic therapy. Herein, we present the longer-term overall survival (OS) results accompanied by additional secondary end points.
The GAMSAT explained
Authors: Phillipa Louise Brothwood
Journal: BMJ (2015)

What it is, who uses it, and how to tackle it The Graduate Medical School Admissions Test (GAMSAT) is used by some universities to assess the suitability of candidates who already have a previous degree (such as bachelors or masters) to study medicine. Seven UK universities require candidates for medicine to take it (box 1). The aim of the GAMSAT is to test your ability to solve problems in different areas, from the humanities to the sciences. The official GAMSAT website states: “GAMSAT evaluates the nature and extent of abilities and skills gained through prior experience and learning, including the mastery and use of concepts in basic science as well as the acquisition of more general skills in problem solving, critical thinking and writing.”1 It is important to remember that you can sit the GAMSAT only once a year. The 2016 test date will be in September and has not been released yet. However, if you subscribe to Student BMJ ’s email alerts we will be sending regular reminders in the lead up to the GAMSAT. #### Box 1: UK medical schools and courses that require candidates to take the GAMSAT
How much study time will I get as a junior doctor?
Authors: Caroline Elton
Journal: BMJ (2015)

Dear Caroline

How much study time will I get when I start foundation training—and how should I go about preparing for it?

Zak Tait, second year medical student, University of Oxford, UK

Caroline replies . . .

When the foundation programme was first devised, the initial intention was that trainees wouldn’t start immediately, sitting postgraduate specialty exams during their foundation years. Although this remains the case with certain specialties—for example, general practice—many trainees who have set their sights on one of the medical or surgical specialties, …
Abstract P3-13-10: Factors impacting surgical option in patients who achieved complete response in the breast after neoadjuvant systemic therapy
Authors: H-W Kou, S-C Shen, S-C Chen
Journal: Cancer Research (2019)

Abstract Background: Neoadjuvant systemic therapy (NST) is the standard treatment for locally advanced breast cancer. Early studies have demonstrated that the rate of breast conservation was significantly increased and NST is now widely applied to operable breast cancer to increase breast conservation rate and to achieve better cosmetic outcome after breast conservative surgery (BCS). For patients who achieved pathologic complete response (pCR), they were perfect candidate for BCS. However, data from prospectively randomized trials have shown that, with the significantly increase of pCR by adding new drugs in the neoadjuvant regimen, BCS rate does not significantly increased. The purpose of current study is to identify factors that have influence on surgical option in patients that have achieved complete response in the breast after NST. Methods: From January 2009 to July 2016, 1150 patients with breast cancer received NST in our institute. There were 103 patients achieved complete response (CR) in the breast and were included in current analysis. Medical records were reviewed regarding to individual surgeon, pre-NST clinicopathologic characteristics, and post-NST image findings. Risk factors for mastectomy were assessed by univariate and multivariate analyses. Results: Of the 103 patients who achieved CR in the breast, 40 of them (38.8%) received mastectomy. In univariate analysis, physician factor, larger initial tumor size, advanced clinical stages, as well as post-NST image findings including skin change, residual tumor ≥3 cm, short nipple-tumor distance, and residual axillary lymph node(LN) on ultrasound and segmental/diffuse distribution of malignant calcification on mammography were associated with more mastectomy. In multivariate analysis, physician factor (OR=5.192, CI [1.562 – 17.257], p=0.021), residual axillary LN on echography (OR=4.000, CI [1.552 – 10.319], p=0.004), and segmental/diffuse distribution of malignant calcification on mammography (OR=7.500, CI [1.819 – 30.916], p=0.018) were independently related to mastectomy in patients who achieved CR in the breast after NST. Conclusion: Physician factor, residual axillary LN and segmental/diffuse malignant calcifications were risk factors for mastectomy in patients who achieved CR in the breast after NST. In addition to embrace current treatment guidelines of surgical management after NST, our data provide valuable additional information to avoid unnecessary mastectomy. Citation Format: Kou H-W, Shen S-C, Chen S-C. Factors impacting surgical option in patients who achieved complete response in the breast after neoadjuvant systemic therapy [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 P3-13-10.
Is medical Erasmus misguided?
Authors: Sarah Rollason
Journal: BMJ (2013)

It has always been harder to justify an Erasmus placement (a European student exchange) for medical students compared with other degree courses. These exchanges make sense in courses that intuitively lend themselves to time abroad, in which arts and foreign language courses feature heavily. But, with no obvious benefits to be gleaned from studying in a hospital that happens to be in an iconic European city, medicine lacks a clear objective in its Erasmus mission statement.

When I left for my placement in Rome, everyone I spoke to was keen to expand on the social and cultural rather than academic benefits. As someone for whom international medicine holds …
Abstract P2-02-16: Not presented
Authors: Y Li, J Chu, J Li, J Tang, Y Yin
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Li Y, Chu J, Li J, Tang J, Yin Y. 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 P2-02-16.
FDG PET/MRI Findings Pointing Toward a Gayet-Wernicke Encephalopathy
Authors: Laura Rozenblum, Marie-Odile Habert, Nadya Pyatigorskaya, Carole Roue-Jagot, Aurélie Kas
Journal: Clinical Nuclear Medicine (2019)

Abstract We report a case of Gayet-Wernicke encephalopathy, revealed by an 18 F-FDG PET/MRI performed in a patient with memory impairment. Metabolism showed no pattern of neurodegenerative disease, but a severe decrease in hippocampus and mammillary bodies (MBs). MRI images analyzed in light of PET findings revealed MB atrophy coupled with signal-intensity alterations, suggestive of a Gayet-Wernicke encephalopathy. Patient was known for alcohol use disorders, and all previous MRI scans were considered as inconclusive. Symptoms improved with correction of thiamine (vitamin B 1 ) deficiency. This report highlights ability of hybrid PET/MRI to investigate small neuronal structures, such as the MBs involved in Gayet-Wernicke disease.