tbuckley/cabot-search huggingface dataset:
Abstract P3-10-25: Clinicopathologic factors associated with pCR to neoadjuvant anti-HER2-directed chemotherapy
Authors: JL Meisel, A Suo, CE Taylor, C Zhang, X Li
Journal: Cancer Research (2019)

Abstract Background: While the use of neoadjuvant therapy has become the standard of care in certain locally advanced breast cancers, questions remain regarding the optimal chemotherapeutic regimen as well as biologic and patient-specific predictors of pathologic complete response. In this study, we examined patient and tumor-specific characteristics associated with increased prediction of pathologic complete response (pCR) to neoadjuvant anti-HER2-directed chemotherapy. Methods: 204 patients who received neoadjuvant anti-HER2-directed chemotherapy at our institution from 2006-2016 were included in this retrospective study. Univariate analyses were performed to analyze the relationships of multiple clinical and pathologic features to pCR rate. Multivariate analysis was also performed to evaluate the relative impact of specific pathologic characteristics on pCR rate. Results: Among 204 patients with HER2 overexpressing breast cancers treated with neoadjuvant chemotherapy, 52.7% achieved pCR. Pathologic complete response was positively associated with high tumor grade (61.0% grade 3 in pCR group vs 39.0% in non-pCR group, P=0.23) and high Ki67 index (mean Ki67 59.1 in pCR group vs 47.4 in non-pCR; P= 0.015). It was also associated with HER2 IHC 3+ (57.1% in pCR group vs 42.9% in non-pCR, p=0.029), HER2 copy number (mean copy number 16.8 in pCR group vs 12.4 in non-PCR, p-0.004), and HER2/CEP 17 ratio (mean ratio 6.42 in pCR group vs 5.17 in non-pCR; P= 0.046). Rates of HER2 FISH positivity were equal in the pCR and non-pCR groups (50.8% vs 49.2%, p=0.062). Multivariate analysis demonstrated that higher Ki67 index and higher HER2/CEP17 ratio are significant predictors of pCR after adjusting for other covariates (odds ratio for Ki67 1.03 (1.06-1.49), p=0.002; for HER2/CEP17 ratio OR 1.26 (1.06-1.49), p=0.009). Conclusions: In HER2 positive breast cancers, a higher Ki67 index as well as higher HER2/CEP17 ratios are associated with an increased pCR rate and may be useful as predictors of response prior to neoadjuvant therapy. Our results also demonstrate HER2 IHC to be a stronger predictor than HER2 FISH of response to upfront therapy. Larger studies would be useful as this association, if confirmed, may have relevance to clinical practice. Citation Format: Meisel JL, Suo A, Taylor CE, Zhang C, Li X. Clinicopathologic factors associated with pCR to neoadjuvant anti-HER2-directed chemotherapy [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 P3-10-25.
Abstract P2-02-09: Not presented
Authors: J An, J Yang, W-H Lee, JB Kim, J-k Kim, H Kim, SH Paek, JW Lee, J Woo, H Kwon, W Lim, NS Paik, Y-K Kim, B-I Moon
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: An J, Yang J, Lee W-H, Kim JB, Kim J-k, Kim H, Paek SH, Lee JW, Woo J, Kwon H, Lim W, Paik NS, Kim Y-K, Moon B-I. 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 P2-02-09.
Corrigendum to “Nanoencapsulation introduces long-acting phenomenon to tenofovir alafenamide and emtricitabine drug combination: A comparative pre-exposure prophylaxis efficacy study against HIV-1 vaginal transmission” [Journal of Controlled Release 294 (2019) 216–225]
Authors: Subhra Mandal, Guobin Kang, Pavan Kumar Prathipati, You Zhou, Wenjin Fan, Qingsheng Li, Christopher J. Destache
Journal: Journal of Controlled Release (2019)
The Apprentices: we’re hired
Authors: Richard Thorley
Journal: BMJ (2013)

Leah Totton’s scheme to establish a chain of high street cosmetic treatment clinics after her victory in the television show The Apprentice has posed several ethical dilemmas. The trivialisation of this enterprise has been condemned by plastic surgeons, although Totton seems to think that her status as a registered medical practitioner will add some repute to the world of facial fillings and skin peelings. It seems unlikely that a 25 year old foundation year doctor will revolutionise an industry that is famously unregulated, and there are other aspects of her plan that are concerning too. Having completed her postgraduate certificate in aesthetic medicine …
Abstract P6-21-04: Targeting PI3Kβ alone and in combination with chemotherapy or immunotherapy in tumors with PTEN loss
Authors: N Owusu-Brackett, M Zhao, A Akcakanat, KW Evans, E Yuca, C Tapia, E Ileana-Dumbrava, F Janku, F Meric-Bernstam
Journal: Cancer Research (2019)

Abstract Background: PTEN functions as a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway to promote balanced cell proliferation, survival and differentiation. PTEN loss occurs across a variety of cancer subtypes; PTEN-deficient tumors are dependent on PI3Kβ activity, making PI3Kβ a compelling target. We evaluated the efficacy of PI3Kβ inhibitor AZD8186 as a single agent and in combination with standard chemotherapy and immune checkpoint inhibitors focused on tumors with loss of PTEN function. Methods: In vitro, cell proliferation assays were performed to determine the half maximal inhibitory concentration (IC50) after 3 days of treatment and to test the effects in combination with standard chemotherapy. Colony formation assays were performed to confirm efficacy of AZD8186 in PTEN-deficient cell lines. Western blot analysis was performed to assess PTEN protein expression and to evaluate effects of AZD8186 on PI3K signaling. In vivo, antitumor efficacy of AZD8186 as a single agent as well as in combination with paclitaxel and anti-PD1 was evaluated. Results: AZD8186 inhibited the cell proliferation of three of ten TNBC cell lines in vitro; PTEN loss was significantly correlated with AZD8186 sensitivity (p= 0.008). Colony formation assay confirmed sensitivity of PTEN-deficient cell lines to AZD8186. AZD8186 inhibited PI3K signaling with decreased expression of pAKT, pGSK3β, pPRAS40 and pS6. AZD8186 treatment of PTEN-deficient cell lines, MDA-MB-436 and MDA-MB-468, resulted in increased apoptosis. Cell proliferation assays demonstrated additive effect of the combination of paclitaxel with AZD8186. AZD8186 significantly enhanced antitumor activity of paclitaxel in MDA-MB-436 and MDA-MB-468 cell-line-derived xenografts, with disease stabilization in the latter. In syngeneic models, AZD8186 enhanced antitumor efficacy of anti-PD1 antibodies in PTEN-deficient BP murine melanoma xenograft (p=0.0073), but not in PTEN-wildtype colon carcinoma, CT26. Conclusion: AZD8186 has single agent efficacy in PTEN-deficient triple negative breast cancer cell lines in vitro, with modest single agent efficacy in vivo. AZD8186 enhanced the antitumor efficacy of paclitaxel and of Anti-PD1 antibodies in vivo. Further study is needed to determine optimal combination therapies for PTEN-deficient solid tumors. Citation Format: Owusu-Brackett N, Zhao M, Akcakanat A, Evans KW, Yuca E, Tapia C, Ileana-Dumbrava E, Janku F, Meric-Bernstam F. Targeting PI3Kβ alone and in combination with chemotherapy or immunotherapy in tumors with PTEN loss [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 P6-21-04.
Abstract P1-15-22: Clinicopathological significance of diversity index for c-MYC copy number variation after primary systemic therapy in breast cancer
Authors: G Kim, YR Chung, HJ Kim, M Kim, S Ahn, SY Park
Journal: Cancer Research (2019)

Abstract Background: Chemotherapy can alter tumor cell populations by exerting selection pressure. This study was performed to evaluate the change in Shannon diversity index for c-MYC copy number variation after primary systemic therapy (PST) and its clinical implications in breast cancer patients treated with PST. Materials and Methods: One hundred and forty-four breast cancer patients who had residual disease after anthracycline- or anthracycline and taxane-based PST were included in the study. Associations between Shannon index for c-MYC copy number variation in pre- and post-PST breast cancer samples and clinicopathologic features of tumors as well as patient survival were analyzed. Results: Among the 119 patients with both pre- and post-PST samples available for comparison, 17 (14.3%) underwent change in c-MYC amplification status and 40 (33.6%) in c-MYC copy number gain status with most cases showing positive to negative conversion. In the whole group, Shannon index for c-MYC copy number variation was decreased in post-PST specimens compared to pre-PST specimens. Especially, the chemo-responsive group showed a more significant decrease in Shannon index after PST. However, there was no difference in diversity indices between pre- and post-PST specimens in the chemo-resistant group. c-MYC copy number gain and high Shannon indices for c-MYC copy number variation in both pre- and post-PST specimens were associated with adverse clinicopathologic features of breast cancer. In survival analyses, high Shannon indices for c-MYC copy number variation in post-PST samples as well as pre-PST samples were revealed as an independent prognostic factor for decreased disease-free survival. Upon subgroup analysis according to hormone receptor status, high Shannon indices before and after PST were associated with adverse clinical outcome in hormone receptor-positive group but not in hormone receptor-negative subgroup. Conclusions: These results suggest that a change in Shannon index for c-MYC copy number variation after PST reflects chemo-responsiveness and that Shannon index after PST can be used as a prognostic factor in breast cancer patients who receive PST. Citation Format: Kim G, Chung YR, Kim HJ, Kim M, Ahn S, Park SY. Clinicopathological significance of diversity index for c-MYC copy number variation after primary systemic therapy in 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 P1-15-22.
Treating victims of a modern war
Authors: Arez Mohamed
Journal: BMJ (2015)

When I planned a work experience placement in my motherland of Iraqi Kurdistan it seemed like an ideal place to get exposure to a medical environment that was different from the NHS. What I did not anticipate was being thrust into a healthcare setting that was coping with fallout of the war between the Islamic State and the Kurds in Iraq.

For my placement I was stationed at Sulaymaniyah Emergency Hospital in the east of Kurdistan, which had not yet been affected to any great extent by conflict. I arrived for my first shift at 7 pm in the emergency department to shadow the director of the emergency hospital and to observe common presentations, similar to those you would see in the United Kingdom. Everything happened at a frantic pace. There was a continuous rush of patients all individually triaged by the …
PLASMA ELECTROLYTE CONCENTRATIONS AFTER THE USE OF 1L POLYETHYLENE GLYCOL BOWEL PREPARATION NER1006: POST HOC ANALYSIS OF RANDOMISED CLINICAL TRIALS
Authors: MA Alvarez-Gonzalez, A Repici, H Thompson, S Mokashi, C Hassan
Journal: Endoscopy (2019)

Bowel preparations contain electrolytes to maintain electrolyte homeostasis after diarrhoea. This post-hoc analysis of randomised, Phase 3 clinical trials assessed plasma sodium concentrations following treatment with the 1L NER1006.
Abstract LB-200: Evidence of efficacy of antibody directed enzyme prodrug therapy (ADEPT) in a Phase I trial in patients with advanced carcinoma.
Authors: Duncan K Wilkins, Astrid Mayer, Surinder K Sharma, Berend Tolner, Roslyn J Francis, Caroline J Springer, Janet A Hartley, Geoff M Boxer, James Bell, Alan J Green, Sweta Parker, Natalie Griffin, Hassan Shahbakhti, Edward Grudus, Kerry A Chester, Richard H Begent
Journal: Cancer Research (2008)

Abstract Background: Antibody Directed Enzyme Prodrug Therapy (ADEPT) uses an antibody linked to an enzyme to deliver enzyme selectively to tumor deposits. When enzyme has localized to the tumor and cleared from the circulation, a low-toxicity prodrug is given. The prodrug is converted into an active cytotoxic drug by the enzyme in tumor deposits. Each targeted enzyme can convert many molecules of the prodrug and a bystander effect is generated. We have previously reported on dose-finding, immunogenicity, and toxicity in a Phase I clinical trial and that the components of ADEPT function as designed in patients (Mayer A, et al. Clin Cancer Res 2006;12:6509-16). Evidence of efficacy is now reported in relation to total prodrug dose (TPD), toxicity, and repeated treatment. Methods: A fixed dose of recombinant fusion protein (MFECP1) was administered intravenously (iv). It consisted of single chain Fv targeting carcinoembryonic antigen (CEA) and carboxypeptidase G2 (Tolner B, et al. Nature Protocols 2006;1:1006-21; Tolner B, et al. Nature Protocols 2006;1:1213-22). Bis-iodo phenol mustard prodrug was given iv when carboxypeptidase activity had cleared from the blood. Patients had measurable, previously treated, advanced malignancy. Either 1, 2, or 3 ADEPT treatments were given over 2 to 10 days. Results: 43 patients with CEA expressing tumors were treated (colorectal, gastro-esophageal, breast, unknown primary, gallbladder, peritoneal, appendix, pancreas). TPD per patient was escalated from 37 mg/m2 to 3226 mg/m2. Thrombocytopenia and neutropenia were the principal side effects, resulting in a maximum tolerated TPD dose of 1200 mg/m2 divided into 2 complete ADEPT treatments. Human anti-enzyme antibody developed in 40% of patients having a single treatment, in 75% of patients after 2 treatments, and in 100% of patients after 3 treatments; it is not yet known whether this will compromise repeated therapy. Efficacy was assessed by 18F FDG-PET using the criteria for partial response defined by Green et al. and shown to predict significant survival prolongation (Eur J Nucl Med Mol Imaging 2008;35:393-406). Four of 9 patients had partial response at TPD ≥ 900 mg/m2. There was a significant correlation between TPD and reduction of tumor FDG uptake (P=0.031). Response was corroborated by falls in serum CA19-9 ≥ 25% in the 3 patients with partial response who had raised levels before treatment. Stable disease by RECIST criteria was seen in 69% of patients having TPD ≥ 900 mg/m2. Conclusions: Evidence of efficacy was shown at a TPD ≥ 900 mg/m2 with clinically significant responses in 44% of patients. These results support the case for conducting a randomized Phase II clinical trial.
Imaging of Activated T Cells as an Early Predictor of Immune Response to Anti-PD-1 Therapy
Authors: Jelena Levi, Tina Lam, Samuel R. Goth, Shahriar Yaghoubi, Jennifer Bates, Gang Ren, Salma Jivan, Tony L. Huynh, Joseph E. Blecha, Roli Khattri, Karl F. Schmidt, Dominique Jennings, Henry VanBrocklin
Journal: Cancer Research (2019)

Abstract Compelling evidence points to immune cell infiltration as a critical component of successful immunotherapy. However, there are currently no clinically available, noninvasive methods capable of evaluating immune contexture prior to or during immunotherapy. In this study, we evaluate a T-cell–specific PET agent, [18F]F-AraG, as an imaging biomarker predictive of response to checkpoint inhibitor therapy. We determined the specificity of the tracer for activated T cells in vitro and in a virally induced model of rhabdomyosarcoma. Of all immune cells tested, activated human CD8+ effector cells showed the highest accumulation of [18F]F-AraG. Isolation of lymphocytes from the rhabdomyosarcoma tumors showed that more than 80% of the intratumoral signal came from accumulation of [18F]F-AraG in immune cells, primarily CD8+ and CD4+. Longitudinal monitoring of MC38 tumor-bearing mice undergoing anti-PD-1 treatment revealed differences in signal between PD-1 and isotype antibody–treated mice early into treatment. The differences in [18F]F-AraG signal were also apparent between responders and nonresponders to anti-PD-1 therapy. Importantly, we found that the signal in the tumor-draining lymph nodes provides key information about response to anti-PD-1 therapy. Overall, [18F]F-AraG has potential to serve as a much needed immunomonitoring clinical tool for timely evaluation of immunotherapy. Significance: These findings reveal differences in T-cell activation between responders and nonresponders early into anti-PD-1 treatment, which may impact many facets of immuno-oncology, including patient selection, management, and development of novel combinatorial approaches.
Abstract P2-08-60: Withdrawn
Authors: S Lee, SH Ahn, BH Son, JW Lee, IY Chung, BS Ko, HJ Kim, J Kim, G Shon
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Lee S, Ahn SH, Son BH, Lee JW, Chung IY, Ko BS, Kim HJ, Kim J, Shon G. Withdrawn [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 P2-08-60.
So this is Christmas
Authors: Isobel Weinberg
Journal: BMJ (2012)

iweinberg@bmj

Welcome to our Christmas issue. As a medical student, you’re probably looking longingly at your winter vacation as it inches slowly towards you. At long last, a chance to take a break from the books, ditch lectures, and escape the 8 am surgical ward round. Once you’ve qualified, though, you won’t be so lucky. Hospitals don’t close for Christmas. In his Careers article (p 24), Guy Rughani interviews the doctors, nurses, and porters who keep a hospital running on 25 December. They aren’t thrilled about having to work while others celebrate, but they cope with doggedness and a large dose of humour. One …
Abstract P5-09-18: Multiple cancer susceptible genes sequencing in BRCA-negative breast cancers with high hereditary risk
Authors: G-T Lang, X Hu, J-X Shi, W Huang, Z-M Shao
Journal: Cancer Research (2019)

Abstract Background Breast cancer susceptibility is strongly associated with a patient's hereditary background. Comprehensive BRCA mutation screening in our cancer center shows a lower BRCA mutation prevalence (9.1%) in Chinese breast cancer patients with hereditary risk. Multiple cancer susceptible genes sequencing can assist in discovering detrimental germline mutation in BRCA-negative breast cancers. Methods From 2005-2014, BRCA-negative breast cancer patients with any two of the following risk factors were recruited: (1) pathological diagnosis of triple-negative breast cancer, (2) male breast cancer, (3) primary bilateral breast cancers in one individual, regardless of synchrony or asynchrony, (4) early-age onset breast cancer (less than or equal to 40 years of age at diagnosis), or (5) patients with a family history of breast and/or ovarian cancer (at least one first- and/or second-degree relative with breast cancer or ovarian cancer). A total of 384 Chinese subjects were screened by next-generation sequencing for 32 breast cancer associated susceptibility genes (APC, ATM, BARD1, BMPR1A, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MEN1, MET, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PALLD, PMS2, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RET, SMAD4, STK11, TP53, VHL). Mutations were classified as pathogenic/likely-pathogenic if they had a truncating, initiation codon or splice donor/acceptor effect, or if pathogenicity was demonstrated in published literature. Results In total, we acquired 39 patients (10.2%) with pathogenic/likely-pathogenic germline mutations, including one carrying two distinct mutations. Major mutant non-BRCA genes were MUTYH (n=11), PTCH1 (n=7), RET (n=6) and PALB2 (n=5). Other mutant genes included TP53 (n=3), RAD51D (n=2), CHEK2 (n=1), BRIP1 (n=1), CDH1 (n=1), MRE11 (n=1), RAD50 (n=1) and PALLD (n=1). In addition, PTCH1 mutation carriers were found to be associated with the clinical features of triple-negative and early-age onset breast cancer. Conclusions Among BRCA-negative breast cancer patients with high hereditary risk in China, 10.2% carried mutations in breast cancer associated susceptibility genes. MUTYH and PTCH1 had relatively high mutation rates (2.9% and 1.8%). Some clinical features might be associated with germline mutations of particular genes in breast cancer. Key words germline mutation, BRCA-negative, hereditary breast cancer, multiple-gene sequencing Citation Format: Lang G-T, Hu X, Shi J-X, Huang W, Shao Z-M. Multiple cancer susceptible genes sequencing in BRCA-negative breast cancers with high hereditary risk [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 P5-09-18.
The Link between Hematopoiesis and Atherosclerosis
Authors: Menno P J de Winther, Esther Lutgens
Journal: New England Journal of Medicine (2019)

Clinical evidence supporting a link between inflammation and atherosclerosis includes the results of the Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS), which showed that targeting inflammation improved cardiovascular outcomes. A recent study involving animal models provides a molecular explanation.
How to interpret skeletal radiographs in adult trauma
Authors: Madhurima Chetan, Tom Turmezei
Journal: BMJ (2015)

Musculoskeletal injuries, including fractures and dislocations, account for more than 60% of diagnoses in the emergency department in England.1 Interpreting a radiograph is a crucial part of diagnosis and management and a vital skill for junior doctors. It relies on good anatomical knowledge, an understanding of radiographic views, and a systematic approach. In this article we aim to enable you to develop these skills and boost your confidence.

For the patient with a fracture or dislocation, a good outcome depends on sound radiographic interpretation. A missed or delayed diagnosis increases long term morbidity and is the commonest reason for litigation.2 The importance of accurate and early radiographic interpretation is well illustrated by the relatively common neck of femur fracture (fig 1).⇓ Non-displaced fractures are stable and usually fixed by cannulated screw pinning, whereas displaced fractures are unstable and require pinning in younger patients and hemiarthroplasty in older patients. A missed non-displaced fracture can progress to a displaced fracture that requires more complex surgical management and has much greater morbidity.



Fig 1 The importance of correctly identifying fractures, exemplified by a case involving the femoral neck. An ambulatory 74 year old woman presented to the emergency department with left hip pain after a fall. Review the anteroposterior views of the left hip. The first radiograph (a) shows normal appearances of the left hip in a younger woman for comparison. Radiograph (b) shows a subcapital neck of femur fracture. Note the cortical discontinuity superolaterally. An irregular sclerotic band running diagonally across the neck represents impaction. This fracture is suitable for pinning, but was missed at initial presentation. The patient re-presented with the inability to bear weight and a shortened, externally rotated left leg. In (c) the follow-up radiograph shows how the fracture in (b) has progressed in displacement; it …