tbuckley/cabot-search huggingface dataset:
Becoming mothers after cancer: Resilience as a protective factor for prenatal attachment and for negative moods during pregnancy.
Authors: Lucia Bonassi, Fedro Peccatori, Chiara Ionio, Giuseppe Nastasi, Eleonora Mascheroni, Alessandra Liuzzo, Flavia Faccio, Camilla Pisoni, Gabriella Pravettoni
Journal: Journal of Clinical Oncology (2018)

e22156 Background: Resilience can be defined as the ability to positively deal with adverse conditions, to overcome difficulties while maintaining relatively good psychological and physical health. Although few studies have explored the psychological aspects of cancer during pregnancy it is plausible that a diagnosis of cancer might interfere with factors that are necessary to deal positively with an ongoing or future gestation. We aim to investigate the possible protective role of resilience in the construction of prenatal attachment and in the intensity of negative moods in pregnant women with a previous or concomitant cancer diagnosis. Methods: 26 pregnant women (25 with breast cancer, 1 with hepatic PEComa) have been enrolled during the last trimester of pregnancy. 20 had a pregnancy after cancer diagnosis, while 6 had cancer occurring during pregnancy. After informed consent, women filled out: the Resilience Scale for Adults, the Prenatal Attachment Inventory, and the Profile of Mood States. Results: Analyses showed positive correlations between resilience factors and prenatal attachment and negative correlations between resilience factors and negative mood states. In particular there was a significant correlation between Social resources and (a) quality of prenatal attachment (r= .44,p= .046), (b) intensity of attachment (r= .45,p= .036); a correlation between Planned future and (a) anxiety (r= -.52,p= .016), (b) fatigue (r= -.43,p= .046); a correlation between Family cohesion and (a) anxiety (r= -.71,p< .001), (b) depression (r= -.56,p= .006), (c) anger (r= -.67,p= .001); a correlation between Social resources and (a) anxiety (r= .45,p= .001). Conclusions: These preliminary data indicate that, it is important to assess resilience and family support in pregnant women with current or past experience of oncological diagnosis. Detailed analysis of which strategies and resources are activated will provide vital information for targeted interventions.
Correlation of survival of NSCLC patients given nivolumab with treatment related-eosinophilia, autoimmunity and previous bevacizumab containing regimens.
Authors: Rocco Giannicola, Graziella D'arrigo, Pierpaolo Pastina, Michele Caraglia, Valerio Nardone, Cirino Botta, Vito Barbieri, Pierfrancesco Tassone, Gabriella Misso, Silvia Zappavigna, Marika Monoriti, Gaetana Porto, Giovanni Tripepi, Pierosandro Tagliaferri, Luigi Pirtoli, Antonia Consuelo Falzea, Pierpaolo Correale
Journal: Journal of Clinical Oncology (2018)

e21008 Background: Programmed-cell-death-receptor-1 (PD-1) blockade by Nivolumab is a promising immunological treatment for metastatic NSCLC patients. It may be associated to adverse events and high costs, thus the identification reliable biomarkers of response is presently a critical point. We carried-out an analysis to investigate the ability of several clinical and immune-biological parameters to predict the outcome of Nivolumab-treated NSCLC patients. Methods: This is a multi-institutional retrospective study including eighty-two NSCLC patients receiving salvage Nivolumab therapy (3mg/kg every 15 days) between September 2015 and December 2017. Kaplan-Meier and Cox-regression analyses were carried-out to correlate PFS and OS with different parameters, including inflammatory markers, auto-antibodies; hormone-profiling; Th1, Th2, Th17-cytokines and lymphocyte subsets. Results: We recorded a PFS and OS of 12.5 [95%CI:9.9-15.0] and 15.3 [95%CI:12.8-17.9] months, respectively, not correlated to histology, number of previous chemotherapy lines, radiotherapy, or TKI use. A better outcome was found in males (OS, HR = 2.3, 95%CI: 1.1-4.8, P = 0.028), in patients who had received chemotherapy + bevacizumab (PFS: 15.5 vs.9.1 months; HR = 0.47, 95% CI: 0.23-0.99,p = 0.047; OS 19.5 vs.11.3 months; HR = 0.34, 95%CI: 0.15-0.80,p = 0.01) and those who showed autoimmunity signs (PFS: 17.2 vs. 6.7 months; HR = 0.30, 95% CI: 0.15-0.57,p < 0.001; OS:20.8 vs. 9.7 days; HR = 0.24, 95% CI: 0.11-0.50, p < 0.001). Finally, Cox analysis revealed that a prolonged OS is associated to a treatment-related increase in eosinophil counts over one month (OS, HR: 0.68, 95% CI: 0.57-0.81, P = 0.031). Conclusions: The antitumor efficacy of Nivolumab in NSCLC patients seems to be empowered by previous exposures to bevacizumab, a mAb able to elicit a VEGF depletion-dependent immune-modulation. This effect could interfere with tumor antigen-cross-priming/presentation, CTL expansion and inflammation, thus promoting antitumor immunization and autoimmunity. Our results offer a strong rationale to design future perspective trials in NSCLC patients.
Analysis of osteosarcoma subtypes by clinical genomic testing to identify clinically actionable alterations.
Authors: John Andrew Livingston, Kristi Posey, Vivek Subbiah, Najat C. Daw, Neeta Somaiah, Vinod Ravi, Shreyaskumar Patel, Robert S. Benjamin, Wei-Lien Wang, Alexander Lazar, Russell Broaddus, Funda Meric-Bernstam, Kenna Rael Shaw, Jason Roszik, Anthony Paul Conley
Journal: Journal of Clinical Oncology (2017)

11019 Background: Genomic testing is being utilized with increasing frequency to identify matched therapies for patients (pts) with advanced disease; however, the utility of such testing has not been defined in osteosarcoma (OS). We report our experience with 36 pts with recurrent/metastatic OS who underwent testing on a genomic testing protocol, including actionable alterations across multiple histologic subtypes of OS. Methods: Standardized hotspot mutation analysis was performed in 36 pts with recurrent/metastatic OS, using either a 46-, 50-gene, or 128-gene CLIA certified multiplex platform. 12 pts had a 200-gene analysis on a companion research protocol. We used the Catalogue Of Somatic Mutations In Cancer (COSMIC) database to identify alterations that are in mutation hotspots in OS or in other cancers. Clinical outcomes were retrospectively collected. Histologic subtype classifications were made by an experienced sarcoma pathologist based upon the pre-treatment and resection specimens. Cases with only metastatic samples available were classified as “other high-grade osteosarcoma.” Additional clinical correlations are ongoing. Results: A total of 36 pediatric and adult pts were analyzed. All osteosarcomas were high grade; the most common osteosarcoma histologic subtypes were chondroblastic, osteoblastic, and other. Samples analyzed were from primary tumor in 15/36 (42%), with the remaining from metastatic specimens (58%). Mutations were identified in 26 pts (72%). The most common mutations were in TP53. An activating PIK3CA E545K mutation was found in chondroblastic OS. Other notable hotspot mutations include a GNAS R201 mutation in osteoblastic osteosarcoma and a KRASG12V mutation in a fibroblastic osteosarcoma. Conclusions: Clinical gene panel sequencing can identify a limited number of potentially actionable mutations in patients with osteosarcoma. Given the heterogeneity of osteosarcoma at the molecular level, clinical genomic testing may be warranted to identify patients for participation on matched clinical trials.
Abstract 17327: Ischemic Skeletal Muscle From Patients With Peripheral Arterial Disease Displays Marked Desialylation of Cell Surface Glycans: Implications for Ischemia-Targeted Gene Therapy
Authors: Arabindra B Katwal, Eric T Mulkey, R John Lye, Brent A French, Brian H Annex
Journal: Circulation (2015)

Introduction: Ischemic skeletal muscle is preferentially targeted after IV injection of AAV9 in mouse models of hind-limb ischemia (HLI). Ischemia is known to induce desialylation of cell surface glycans, unmasking the cellular receptor for AAV9 and resulting in significantly higher levels of selective gene expression in ischemic vs non-ischemic muscle. To assess clinical relevance, we compared the differential distribution of sialylated and desialylated cell surface glycans in skeletal muscle biopsies from peripheral arterial disease (PAD) patients and normal controls. Methods: Gastrocnemius (GA) muscle samples from PAD patients and normals (n=29 each) were biopsied under IRB-approved protocols. Muscle sections were stained using the lectins MAL-I and ECL. MAL-I binds to α2,3-sialylated glycans whereas ECL binds to desialylated galactose residues on cell surface glycans. Lectins were labeled with Streptavidin-Alexa-488 (red) for MAL-I and SA-555 (green) for ECL, and visualized using fluorescence microscopy. Quantification of mean fluorescence signal intensity of lectin staining was performed on each section. Results: Visually, MAL-I staining was markedly higher and ECL staining lower in non-ischemic GA from normals when compared to ischemic GA from PAD patients (Figure). The ratio of MAL-I to ECL integrated fluorescence intensity in the ischemic muscles from PAD patients (1.13 ± 0.13) was significantly lower than the same ratio in non-ischemic muscles from normals (1.58 ± 0.14, p&lt;0.02). Conclusions: Desialylation of cell surface glycans is significantly higher in ischemic skeletal muscle from PAD patients, consistent with previous work in a mouse model of HLI. This desialylation can potentially be exploited to treat human PAD with gene therapy, since these desialylated cell surface glycans serve as cell surface receptors for AAV9 and provide for efficient and selective gene transfer to ischemic skeletal muscle following systemic or local delivery.
Crosstalk between hesperetin and miR-486-5p in triple-negative breast cancer (TNBC): An approach towards precision medicine
Authors: R.M. Abdallah, R.A. Youness, N. El Meckawy, A. El Sebaaei, A.A. Abdelmotaal, R.A. Assal
Journal: Annals of Oncology (2018)

Background: Hesperetin an aglycone extracted from citrus fruits, acts as a novel therapeutic agent in breast cancer (BC). TNBC patients showed the most heterogeneous molecular profiles portrayed with inferior overall survival. This highlights the emerging need of precision medicine to unravel the inter-wined molecular circuits in TNBC patients. Our group has uncovered the tumor suppressor activity of miR-486-5p in liver cancer and BC. However, its role in tuning the metastatic behaviour of TNBC cells remains to be unveiled. This study aims at investigating the interplay of hesperitin and miR-486-5p as a novel therapeutic approach towards achieving a personalized treatment code for TNBC patients. Methods: Breast tissues were collected from 26 BC patients. ER, PR and HER-2 expression was quantified using immunohistochemistry. MDA-MB-231 TNBC cells were treated with serial dilutions of hesperitin. miR-486-5p loss and gain of function experiments was performed using lipofection technique. Functional analysis experiments were carried out such as MTT, colony forming and wound closure assays 48 hrs post-treatment. 5-Fluro uracil was used as a positive control. Total RNA extraction was performed followed by reverse transcription into cDNA which was quantified using qRT-PCR. Unpaired student's t-test was performed using GraphPad 5.0. Results: miR-486-5p was down-regulated in 100% of BC patients. TNBC patients showed a selective diminished miR-486-5p levels compared to non-TNBC patients. Hesperetin markedly decreased MDA-MB-231 cellular viability and clonogenicity compared to vehicle control. miR-486-5p mimics repressed cellular viability, clonogenicity and metastatic potential of TNBC cells thus supporting its reported tumor suppressor activity. While anti-miR-486-5p resulted in an increase in TNBC hallmarks. Interestingly, a potential crosstalk between hesperitin and miR-486-5p was witnessed in MDA-MB-231 where hesperitin markedly increased miR-486-5p expression. Conclusions: Hesperitin is a novel anti-neoplastic agent which mediates its anti-proliferative activity through inducing miR-486-5p levels thus efficiently harnessing TNBC progression and hijacking its metastatic potential. Legal entity responsible for the study: German University in Cairo, GUC. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
5-fluourouracil-leucovorin chemoradiotherapy to the adjuvant treatment of operable gastric cancer: A retrospective data from a Brazilian reference cancer institution.
Authors: Ramon Andrade De Mello, Mario Vilany Gomes Bonfim Oliveira, Jailson de Souza Oliveira, Filipe Marques de Oliveira, Jose Fernando Bastos
Journal: Journal of Clinical Oncology (2016)

e15540 Background: Adjuvant chemoradiotherapy (CRT) previously showed clinical benefits for patients whom were submitted to gastrectomy due to operable gastric cancer. Our aim was to assess the 10 years clinical practice experience regarding this multi-modality approach. Methods: The institutional ethical committee approved the study. It was registered in the Brazilian National Ethical Committee Platform. In the dataset, 1853 gastric cancer patients were treated in the period between January 2002 and December 2012. Sixty-six out of ninety-six eligible patients were treated after the surgery with 5-flourouracil (5FU) at a dose of 425 mg per square meter of body-surface area on day 1 to 5 and leucovorin (LV) at a dose of 20 mg per square meter of body-surface area on day 1 to 5 followed by 4500 cGy of radiation given in twenty five fractions at 180 cGy per day. Results: D1 gastrectomy was performed in 96.9% of the patients. Pathological node positive disease was reported in 76.9% and was not associated to an overall survival (OS) benefit: harzard ratio 1.576 (95%, confidential interval, CI, 0.209 - 4.915). All patients commenced the chemotherapy with full dose of 5FU/LV and 66.7% tolerated six cycles. Most of patients tolerated the full dose of radiotherapy (89.1%). 51.5% of the enrolled patients presented grade 3/4 adverse events, such diarrhea (27.3%), neutropenia (10.6%), emesis (7.6%), thromboembolic effects (4.5%) and anemia (3%). The median progression-free-survival (PFS) was 14 months (95% CI, 11.311 - 16.689) and the median OS was 31 months (95% CI, 18.077 - 43-923). Furthermore, 47% presented disease progression and the cancer-related mortality was 52%. Conclusions: Our retrospective cohort showed slightly inferior clinical outcomes when compared to the classical INT-0116 trial results: PFS 14 versus 19 months; and OS 31 versus 36 months, respectively. Despite the extrapolative comparative data, our cohort suggests that adjuvant CRT outside the clinical trial may not give a provision of similar outcomes and therefore it is important to consider alternative feasible treatments, perhaps peri-operative chemotherapy or adjuvant chemotherapy.
The utility of optical coherence tomography for diagnosis of basal cell carcinoma: a quantitative review
Authors: N. Reddy, B.T. Nguyen
Journal: British Journal of Dermatology (2018)

Optical coherence tomography (OCT) is a noninvasive near‐infrared light imaging technology that can be utilized to diagnose basal cell carcinomas (BCCs) based on specific morphological features. To conduct a quantitative review using tumour‐level data from published studies to assess: (i) the in vivo diagnostic accuracy of different OCT systems; (ii) correlation between OCT features and histopathological diagnosis; and (iii) factors that impact the accuracy of tumour depth estimation. Primary tumour‐level data were extracted from published studies on the use of time‐domain (TD‐OCT), frequency‐domain (FD‐OCT) and high‐definition (HD‐OCT) systems for diagnosis of BCCs. Quality assessment was performed using the Newcastle–Ottawa Scale and the Cochrane Risk of Bias Tool. Sensitivity and specificity for diagnosis of BCC, prevalence of morphological features and correlation of tumour depth between OCT and histopathology were analysed. In total, 901 BCCs from 31 studies were included. The sensitivity and specificity were 89·3% and 60·3% overall, and were highest for FD‐OCT (93·7% and 61·4%, respectively). The most prevalent morphological features were lobular pattern (80·2%, 315 of 393 tumours) and hyper‐reflective peritumoral stroma (51·7%, 203 of 393). Concordance between OCT and histopathological tumour depth categories was moderate (Pearson coefficient 0·48); it was highest for tumours < 1 mm and those on the extremities. The overall bias was 0·075 mm with an agreement range from −0·88 to 1·03 mm. HD‐OCT and FD‐OCT were superior to TD‐OCT at identifying morphological features, but not at tumour depth estimation. OCT is a viable tool for in vivo diagnosis of BCCs. FD‐OCT and HD‐OCT outperformed TD‐OCT in diagnostic accuracy and detection of morphological features, but not tumour depth estimation.
TCT-247 Reducing Radiation Exposure to Operators During Invasive Cardiac Procedures with a Novel Lead-Based Arm-Board (RADAR)
Authors: Tawfiq Choudhury, Samual Hayman, Andrew McLellan, Rodrigo Bagur, Shahar Lavi, Amir Solomonica, None Zeev Israeli, Andrew Yadegari, Terrence McPherson, Patrick Teefy, Pallav Garg
Journal: Journal of the American College of Cardiology (2018)
P04.63 ENO1 ist downregulated in meningiomas and upregulated in low grade gliomas
Authors: D T D Dinh, S Kuhl, G Röhn, R Goldbrunner, M Timmer
Journal: Neuro-Oncology (2018)

Cancer cells reorganize their metabolic pathways to gain nutrients such as glucose and glutamine because of their anabolic needs. Anaerobic glycolysis increases the total glycolysis in hypoxic conditions and normal oxygen conditions, which is known as the “Warburg effect”. The α-Enolase (ENO1), a glycolytic enzyme, produces ATP, through converting 2-phosphoglycerat to phosphoenolpyruvate and contributes to the “Warburg effect”. In various tumors as breast cancer, pancreatic cancer and gastric cancer the expression of ENO1 is augmented. The aim of the study is to examine whether ENO1 is also higher expressed in gliomas and meningiomas. It was also of interest whether the therapy with temozolomide in gliomas changes the concentration of ENO1. To determine the expression of ENO1 in meningiomas, qPCR and Western Blots were performed. All experiments were done in triplicates.ß-Actin and MRLP19 were used as reference genes. The meningioma samples were sorted in grad I, grade II, grade III. Non-tumorous brain tissue was used as control group. The protein level of ENO1 in glioma were measured through Western Blot. The glioma samples used were sorted in non-tumorous brain tissue, grade II, grade III, secondary and primary glioblastoma with and without temozolomide. All samples used for Western Blots were incubated with mouse monoclonal anti-ENO1 antibody. A secondary HPR-linked anti-mouse antibody was used to make the lanes visible. ß-Actin was used as a loading control antibody. The qPCR data showed a higher ENO1 expression in control samples than grade I meningioma (5.6 ± 2.403 vs. 2.907 ± 1.931, p= 0.002). In grade II and III the concentration was higher compared to grade I (4.994 ± 2.064 vs. 2.907 ± 1.931, p= 0.002; 4.98 ± 2.385 vs 2.907 ± 1.931vs, p= 0.01). The Western Blot data showed a higher ENO1 concentration in control samples than in meningioma tissues (control: 1.262 ± 0.256 vs. grade I: 1.037 ± 0.16, p=0.047; control vs. grade II: 0.961 ± 0.119, p= 0.012; control vs. grade III: 0.966 ± 0.1311, p= 0.015). Western Blots showed an upregulation of ENO1 in grade II gliomas compared to all groups (2.00 ± 0.66 vs. control: 1.00 ± 0.247, p=0.0031; vs. grade III: 1.173 ± 0.369, p= 0.010; vs. secondary GBM: 0.902 ± 0.199, p= 0.0006). Secondary GBM had lower ENO1 concentration than treated secondary GBM (0.902 ± 0.199 vs. 1.231 ± 0.199, p=0.021). An enhanced expression could be seen in treated secondary GBM compared to treated primary GBM (1.231 ± 0.199 vs. 0.902 ± 0.1336, p= 0.029). In meningiomas no difference was found between the different grades on the posttranslational level. However, ENO1 level was lowered in meningiomas compared to healthy tissue. Grade II gliomas showed higher ENO1 expression than high grade gliomas. This data suggests that ENO1 could play a role in brain tumors.
Outcomes of older acute myeloid leukemia (AML) patients receiving hypomethylating therapy versus standard induction chemotherapy (IC) prior to allogeneic hematopoietic cell transplantation (HCT).
Authors: Tao Zou, Ashley M. Perry, Peter G Kim, Maura A. Blaney, Jennifer Lombardi Story, Andrew Mark Brunner, Yi-Bin Albert Chen, Amir Tahmasb Fathi
Journal: Journal of Clinical Oncology (2016)

e18526 Background: Patients with AML are typically treated initially with IC, often followed by consolidation with HCT. Hypomethylating agents (HMA) are an alternative initial therapy for patients who are less fit at diagnosis. Whether the choice of therapy prior to HCT affects outcomes after HCT is unknown. We performed a retrospective study to compare outcomes after HCT for older AML patients treated with IC vs. HMA prior to HCT. Methods: We identified patients over age 60 with AML who underwent HCT from 2008-2014 while in first remission (CR1). Patients treated with HMA were in the HMA group and patients given IC were in the IC group. We compared the age at diagnosis and baseline AML characteristics between the groups with the t test or Chi-squared test. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS) from time of HCT, both calculated with the log-rank test. Results: We identified 7 HMA and 63 IC patients. No significant differences existed in median age at diagnosis (age 66 for both, t test) or baseline AML characteristics (Table I, Chi-squared test). All HMA patients achieved CR1 prior to HCT with a median of 3 cycles of therapy (range of 2-9). 4 of the 7 patients (57%) in the HMA group are still alive and without relapse at 71, 38, 29, and 17 months after HCT. The remaining 3 HMA patients died during follow up: one with relapse at +310 days, one from GVHD 25 months after HCT, and one from sepsis during conditioning at day +32. Among IC patients, estimated 2-year OS was 49% and 2-year PFS was 43% (log-rank test). Conclusions: Select patients who achieve CR from initial HMA therapy can successfully undergo HCT. Although this series is small, our findings suggest that outcomes after HCT for patients treated initially with HMA are similar to those treated with IC. Thus, older AML patients who are otherwise fit may benefit from consideration for HCT. Baseline characteristics. Characteristics (%) IC HMA p value Cytogenetic risk p=0.68 Favorable 3 (5%) 0 Intermediate 48 (76%) 5 (71%) Adverse 11 (18%) 2 (29%) FLT3 status p=0.49 ITD 11 (18%) 0 TKD 5 (8%) 0 NPM1 status p=0.54 Mutant 15 (24%) 3 (42%)
Digital image analysis as an aid in the assessment of the combined positive score in ovarian carcinoma.
Authors: Karina Kulangara, David Calcagno, Scott Boyer, Debra Ann Hanks, Holly Yamada
Journal: Journal of Clinical Oncology (2017)

e14584 Background: Developing scoring methods for PD-L1 to identify patients who will respond effectively to anti-PD1 therapy is key in the development of companion and complementary diagnostic assays. The Combined Positive Score (CPS) is an elegant method for the evaluation of PD-L1 expression in solid tumors. CPS includes the number of PD-L1 positive cells (tumor, lymphocytes and macrophages) in relation to total tumor cells. The accurate manual capturing of total number of tumor cells can be a challenge to pathologists. Methods: Image analysis was used to evaluate possibledifferences in tumor density for well, moderately, and poorly differentiated ovarian epithelial serious carcinomas. Multiple regions of interest of 158 hematoxylin-stained specimens were analyzed. Algorithm parameters were systematically adjusted to minimize mean differences in tumor count relative to manually counted scores in small, user-selected regions of 33 representative specimens. Results: The average nuclei count ranged between 2000 and 7000 with ~50% falling between 4.0-5.5 x 10 3 . Conclusions: Digital image analysis of nuclear quantification has been shown to be a useful tool to aid the pathologist with the correct assessment of the CPS score.