tbuckley/cabot-search huggingface dataset:
A miRNA-based signature predicts development of disease recurrence in HER2 positive early breast cancer after adjuvant trastuzumab-based treatment.
Authors: Feng Du, Peng Yuan, Jiayu Wang, Fei Ma, Yang Luo, Binghe Xu
Journal: Journal of Clinical Oncology (2016)

e12070 Background: Adjuvant trastuzumab is the standard treatment for early HER2 positive breast cancer. However, 15%-22% of patients still suffered disease recurrence after adjuvant anti-HER2 treatment. A molecular prognostic model that can reliably stratify patients by risk of developing disease recurrence is urgently needed. Methods: All the patients included were diagnosed as HER2-postive breast cancer and received radical surgery followed by adjuvant trastuzuamb treatment. Using miRNA microarrays, we analyzed the FFPE tumor tissue from14 patients (7 recurrence vs.7 non-recurrence) and identified nine miRNAs that were differentially expressed. Then, we validated the expression of these miRNAs using qRT-PCR in training set (n = 101), and built the miRNA-based classifier using the Cox regression model. We further confirmed the prognostic accuracy of this signature in an internal testing set (n = 57), and an external independent testing set (n = 53) Results: We identified a two-microRNA signature that classify patients into those at high risk of disease progression (high-risk group), and those at low risk (low-risk group).DFS was significantly different between the two groups in each set of patients. In the training set, 5-year DFS was 89.2% for the low-risk group, and 59.0% for the high-risk group (hazard ratio [HR] 5.35, 95% CI 2.13-13.44; p < 0.001).In the internal testing set, 5-year DFS was 87.5% for the low-risk group, and 45.8% for the high-risk group (HR 3·71, 95% CI 1.08–12.74; p = 0.025), and in the external independent testing set, that was 80.1% for the low-risk group and 38.9% for the high-risk group (HR 3·43, 95% CI 1.35–8.69; p = 0.006). In the combined analysis of all patients (n = 211), the two-miRNA signature was an independent prognostic factor for prognosis, and had better predictive value than other clinicopathological factors. In combination with TNM stage, the model demonstrated the highest prognostic accuracy (AUC = 0.711, 95%CI 0.634-0.787). Conclusions: Our two-miRNA signature is a reliable prognostic and predictive tool for disease recurrence in patients with HER2 positive breast cancer who received adjuvant trastuzumab-based treatment.
Breast tumor location in <i>BRCA</i> mutation carriers and implications for prevention.
Authors: Ava Hosseini, Laura Esserman, Anne M. Wallace, Amal Khoury, Alfred Au, Rita Mukhtar
Journal: Journal of Clinical Oncology (2017)

e13048 Background: Although pathogenic mutations in the BRCA gene are known to confer a high risk of breast cancer, close to 65% of mutation carriers do not opt for prophylactic mastectomy. These women are managed with intense screening, which does not aid in prevention. Breast reduction mammoplasty is a surgical technique shown to reduce breast cancer risk (0.39-0.61 relative risk reduction), and can be modified to target specific areas of the breast. Given that most sporadic breast cancers involve the upper outer quadrant, we wondered if a majority of tumors in BRCA mutation carriers would also be confined to one quadrant, or if they would be equally distributed throughout the breast given the high baseline risk present. Identifying a particularly high risk area of the breast could potentially allow for the use of targeted cosmetic mammoplasty as a novel method of risk reduction. Methods: We reviewed imaging reports on 103 consecutive patients with BRCA mutations and invasive breast cancer, and categorized tumor location by quadrant. Tumors spanning &gt; 1 quadrant were classified as being in both. Bilateral cancers were counted separately. Categorical variables were compared with the chi-squared test. Results: Mean age at breast cancer diagnosis was 44 years. Mean tumor size was 2.2 cm (0.1-7cm) with mean distance from the nipple of 4.8 cm (1-12 cm). 92% of tumors were invasive ductal carcinoma, 46% were hormone receptor positive, 10% Her2 positive, and 44% triple negative. 70% of the tumors were unicentric. Tumors were significantly more likely to be in the upper outer quadrant (54%, with the other quadrants having 11-17% of tumors respectively) whether or not multicentric tumors were included in the analysis (p &lt; 0.00001). Her2 positive tumors were more likely to be multicentric than other subtypes (p = 0.021). Conclusions: More than half of breast cancers in BRCA mutation carriers form in the upper outer quadrant, suggesting that breast reduction mammoplasty targeting removal of the upper outer quadrant could significantly reduce breast cancer risk. For those women who choose not to have prophylactic mastectomies or are not yet ready, these data support an intermediate step to help decrease breast cancer risk, which warrants further study.
Phase I dose-escalation trial of Sym004, a mixture of two anti-EGFR antibodies, in Japanese patients with advanced solid tumors.
Authors: Ken Kato, Takashi Kojima, Kentaro Yamazaki, Kei Muro, Hiroki Hara, Keisho Chin, Thomas Goddemeier, Morihiro Watanabe, Toshihiko Doi
Journal: Journal of Clinical Oncology (2016)

2522 Background: Sym004 is a 1:1 mixture of two chimeric IgG1 antibodies targeting non-overlapping epitopes of the epidermal growth factor receptor (EGFR). Binding of both antibodies to EGFR leads to its internalization and degradation. The resulting down-regulation of EGFR results in antitumor activity that is superior to that of cetuximab and panitumumab in preclinical models; Sym004 can also overcome acquired resistance to cetuximab in vivo. We have evaluated the safety of Sym004 in Japanese patients (pts) with advanced solid tumors. Methods: Japanese adults aged ≥ 20 years with refractory or recurrent late-stage solid tumors, ECOG status of 0 or 1, and life expectancy of at least 3 months were eligible for the dose-escalation part of the trial (Part A). Sym004 doses tested were 6 mg/kg weekly (n = ’3+3’), 9 mg/kg loading dose followed by 6 mg/kg weekly (n = 6), 12 mg/kg weekly (n = 6), and 18 mg/kg q2w (n = 6). An expansion cohort of pts with esophageal squamous cell carcinoma (ESCC) (Part B) was enrolled at the Sym004 dose recommended based on part A. The primary objective was the safety and tolerability of Sym004 in Japanese pts. Secondary objectives included antitumor activity and pharmacokinetics. Results: 51 pts were treated (male/female: 39/12; median age 62 [40-73] years; ECOG performance status 0/1: 32/19). No dose-limiting toxicities were observed in Part A. A Sym004 dose of 12 mg/kg weekly was selected for use in Part B (n = 30). Pts in Part B received a median of 7 weeks of Sym004 therapy. All Part B pts had treatment-related adverse events (AEs); 18 had grade ≥ 3 AEs and 5 had serious AEs (cardiac arrest, lung infection, interstitial lung disease, toxic skin eruption, blood creatinine increase). Two pts had treatment-related AEs resulting in death (cardiac arrest and blood creatinine increase). 5 pts had a best overall response of partial response, 12 stable disease, 12 disease progression (1 pt not evaluable). The objective response rate was 16.7% (95% CI: 5.6–34.7%). Conclusions: Sym004 therapy was well tolerated with no DLTs at any dose studied. Evidence of antitumor activity, with objective responses, was observed in the expansion cohort of pts with advanced ESCC. Clinical trial information: NCT01955473.
Parallel mutation screening and methylation quantification improves the molecular diagnostic yield for colorectal cancer.
Authors: Jun Min, Xiaoliang Lan, Zi Qin, Xiaojie Liu, Sufen Zhang, John Nguyen, Athurva Gore, Rui Liu, Li Liang
Journal: Journal of Clinical Oncology (2017)

e13003 Background: Recurrent somatic mutations and methylation patterns have previously been identified as biomarkers for non-invasive screening of colorectal cancer (CRC). However, most clinical screening assays have focused on a limited number of genomic loci, potentially reducing sensitivity and specificity. Here, we examined the potential utility of using an expanded set of mutation and methylation markers to improve screening accuracy of CRC. Methods: Pairs of colorectal tumor and tumor-adjacent tissues were resected from 41 CRC patients in Nanfang Hospital (NFH), China. The DNA was extracted, processed, and sequenced with Singlera Genomics’ OncoAim assay, which detects mutations across 59 genes implicated in cancer and quantifies the methylation level for key CRC genes. Matched pre- or post-surgery plasma samples were also collected and processed in parallel. Results: Thirty-eight tumor samples (93%) contained somatic mutations with greater than 5% allele frequency, while twenty-nine tumor samples (71%) contained aberrant methylation patterns. Among the tumor-adjacent samples, six contained somatic mutations and eight contained epigenetic abnormalities. Out of three tumor samples without any detectable somatic mutations, one showed an aberrant methylation pattern. Importantly, aberrant methylation patterns in tumor samples were also detected in matched plasma samples. Conclusions: Parallel mutation screening and methylation analysis not only improves the diagnostic yield, but also paves the way for non-invasive monitoring on patients with no common mutations.
Abstract P5-14-09: Luminal A breast cancer: Is it really a “good prognosis” disease? Prelimary results of the GIM-13 - AMBRA study
Authors: ME Cazzaniga, G Mustacchi, M De Laurentiis, O Garrone, M Donadio, L Del Mastro, L Latini, L Livi, A Michelotti, F Montemurro, C Natoli, N Riccardi, A Turletti, M Giordano, S De Placido, L Biganzoli, P Pronzato, P Marchetti
Journal: Cancer Research (2017)

Abstract This abstract was not presented at the symposium.
Clinical assessment versus research methods in the assessment of suicidal behavior
Authors: K M Malone, K Szanto, E M Corbitt, J J Mann
Journal: American Journal of Psychiatry (1995)

This study examined how accurately routine inpatient clinical assessments documented a history of overt suicidal behavior in inpatients with a diagnosis of major depressive episode. Secondary questions involved the exploration of possible factors influencing the quality of routine clinical documentation of suicidal behavior, such as lethality of attempts, axis II comorbidity, and presence of recent suicidal behavior.Hospital records for 50 patients, known to have a history of suicidal behavior on the basis of research ratings, were reviewed to assess reporting of the number of lifetime suicide attempts, suicidal ideation and planning behavior, most medically lethal suicide attempt, and family history of suicidal behavior. These measures of suicidal behavior were compared with a comprehensive research assessment, completed concurrently and independently.At admission clinicians failed to document a history of suicidal behavior in 12 of 50 patients identified by research assessment as depressed and as having attempted suicide. Fewer total suicide attempts were clinically reported than in research data. Documentation of suicidal behavior was least accurate in the physician discharge summary and was most accurate on hospital intake assessment, which employed a semistructured format for recording clinical information including suicidal behavior.A significant degree of past suicidal behavior is not recorded during routine clinical assessment, and the use of semistructured screening instruments may improve documentation and detection of lifetime suicidal behavior. The physician discharge summary must accurately document suicidal behavior, since it best identified a high-risk population for out-patient clinicians responsible for follow-up.
Anterior pallidal deep brain stimulation for Tourette's syndrome: a randomised, double-blind, controlled trial
Authors: Marie-Laure Welter, Jean-Luc Houeto, Stéphane Thobois, Benoit Bataille, Marc Guenot, Yulia Worbe, Andreas Hartmann, Virginie Czernecki, Eric Bardinet, Jerome Yelnik, Sophie Tezenas du Montcel, Yves Agid, Marie Vidailhet, Philippe Cornu, Audrey Tanguy, Solène Ansquer, Nematollah Jaafari, Emmanuel Poulet, Giulia Serra, Pierre Burbaud, Emmanuel Cuny, Bruno Aouizerate, Pierre Pollak, Stephan Chabardes, Mircea Polosan, Michel Borg, Denys Fontaine, Bruno Giordana, Sylvie Raoul, Tiphaine Rouaud, Anne Sauvaget, Isabelle Jalenques, Carine Karachi, Luc Mallet, M.L. Welter, E. Cuny, P. Derkinderen, D. Fontaine, J.L. Houeto, I. Jalenques, L. Mallet, P. Pollak, S. Thobois, M.L. Welter, A. Bissery, H. Oya, E. Bardinet, J. Yelnik, M.L. Welter, A. Buot, J.L. Houeto, V. Czernecki, I. Jalenques, S. Tezenas du Montcel, A. Tanguy, M. Hajji, J.L. Houeto, L. Mallet, A. Tanguy, S. Tezenas du Montcel, M.L. Welter, C. Karachi, L. Mallet, M.L. Welter, A. Hartmann, V. Czernecki, J. Yelnik, E. Bardinet, Y. Agid, Y. Worbe, D. Dormont, A. Buot, M. Vidailhet, P. Cornu, B. Aouizerate, P. Burbaud, E. Cuny, I. Jalenques, F. Durif, C. Fauchon, F. Rondepierre, P. Derost, M. Aya Kombo, M. Polosan, S. Chabardès, A. Krainik, P. Krack, B. Piallat, P. Pollak, S. Thobois, M. Guenot, E. Poulet, H. Klinger, G. Serra, E. Broussolle, T. Rouaud, A. Sauvaget, P. Derkinderen, P. Damier, S Raoul, D. Fontaine, M. Borg, B. Giordana, M.-N. Magnie-Mauro, J.L. Houeto, N. Jaafari, B. Bataille, S. Ansquer, I. Benatru, A. Fradet, E. Dugast, A. Ouerdani, E. Rabois, M. Quintin, S. Palfi
Journal: The Lancet Neurology (2017)
The rational use of detection of CTC and serum HER2 ECD for HER2-positive advanced breast cancer patients.
Authors: Jinmei Zhou, Tao Wang, Yi Liu, Huiqiang Zhang, Shaohua Zhang, Li Bian, Santai Song, Zefei Jiang
Journal: Journal of Clinical Oncology (2016)

e12084 Background: Circulating tumor cell (CTC) and serum HER2 ECD can reflect tumorous biological information in different aspects, however their clinical significance for HER2-positive advanced breast cancer receiving anti-HER2 therapy remain unclear. We performed this prospective, monocenter, double-blinded study to investigate the potential clinical significance of detection of CTC and serum HER2 ECD for advanced breast cancer patients with histological HER2-positivity. Methods: A total of 155 eligible patients were enrolled in the present study from April 2012 to October 2015. We used Cell search system and ADVIA Centaur System to detect CTC and serum HER2 ECD respectively. Patients received systemic treatment according to national and international guidelines. Results: Forty nine (31.6%) patients had ≥ 5 CTC, One hundred and twenty three (79.4%) patients had serum HER2 ECD values of at least 15ng/ml, forty seven (30.3%) patients had both elevated CTC and ECD values, thirty (19.4%) patients had both normal CTC and ECD values. All patients received anti-HER2 therapy, patients with both normal CTC and serum HER2 ECD values exhibited a significantly longer median PFS than patients with both elevated values (9.0 months versus 4.1 months, p = 0.043) and exhibited a trend toward longer PFS compared with patients with elevated CTC or ECD values (9.0 months versus 5.0 months, p = 0.075), patients with both or one elevated values showed similar median PFS (4.1 months versus 5.0 months, p = 0.366). For patients with elevated ECD values , those with ECD decreasing ≥ 20% after therapy had significantly longer PFS than others (9.4 months versus 2.4 months, p < 0.0001) Conclusions: Patients with both normal CTC and serum HER2 ECD values exhibited longer median PFS than others, the dynamic monitor of ECD values had prognostic significance for patients with initial elevated values.
Якість життя хворих на неспецифічний виразковий коліт із супутнім субклінічним атеросклерозом
Authors: I.V. Chopei, T.M. Ternushchak, S.S. Filip
Journal: GASTROENTEROLOGY (2020)

Метою дослідження була оцінка якості життя хворих на неспецифічний виразковий коліт (НВК) середнього ступеня тяжкості із супутнім субклінічним атеросклерозом до та після лікування статином у комбінації з омега-3 поліненасиченими жирними кислотами (омега-3 ПНЖК).У хворих на НВК із супутнім атеросклерозом встановлене погіршення якості життя переважно за компонентами фізичного здоров’я (питальник SF-36), яке прямо пропорційне ступеню вираженості атеросклерозу (р &lt; 0,05). У процесі комбінованого лікування статинами та омега-3 ПНЖК вірогідно покращувалися показники не тільки фізичного, але й незначно — психічного здоров’я (р &lt; 0,05). Аналізуючи дані за спеціалізованим питальником GSRS, ми визначили, що зростання якості життя покращилось за трьома із п’яти шкал — абдомінального болю, диспептичного та діарейного синдромів (р &lt; 0,05).
Telomerase Inhibition with Imetelstat Eradicates β-Catenin Activated Blast Crisis Chronic Myeloid Leukemia Stem Cells
Authors: Wenxue Ma, Cayla N Mason, Ping Chen, Nathaniel Delos Santos, Jiang Qingfei, Elisa Lazzari, Fei Huang, Larisa Balaian, Catriona H.M. Jamieson
Journal: Blood (2016)
Engrailed-2 (EN2) protein expression and prognosis in bladder cancer following radical cystectomy (RC).
Authors: Simon J. Crabb, James Douglas, Nicola E. Annels, Richard Morgan, Graham Packham, Hardev S. Pandha
Journal: Journal of Clinical Oncology (2014)

4545 Background: Dysregulation of various developmental genes is associated with urological malignancies. In particular, HOXB13 overexpression is associated with aggressive invasive bladder cancer. Engrailed-2 (EN2), a member of the HOX gene family, was recently shown to be expressed and secreted by non-muscle invasive bladder cancer (NMIBC) leading to its development as a potential urinary diagnostic marker. However, the role of EN2 as a prognostic marker in muscle invasive advanced bladder cancer is unknown. Methods: We assessed EN2 protein expression in a tissue microarray of consecutive bladder cancer RC samples from a UK center. EN2 expression was prospectively dichotomised as positive (3+ nuclear and cytoplasmic staining) or negative. Univariate analyses of known prognostic factors and EN2 for survival outcomes from date of RC were by the Kaplan Meier method and log rank test. Statistically significant variables were then assessed by multivariate Cox regression. p values < 0.05 were considered statistically significant. Results: 226 samples were eligible for inclusion (median age 72, range 33-87; 76.1% male, 90.3% pure/predominant transitional cell carcinoma). EN2 expression status was positive in 39 (17%) cases and negative in 160 (71%). No scoring was possible (mostly for missing cores) in 27 (12%) cases. Overall survival was reduced in patients with positive vs. negative EN2 staining (median survival 2.23 vs. 5.23 years, p=0.007) which was maintained in multivariate analysis (hazard ratio 1.61, 95% CI 1.05-2.48, p=0.03). Bladder cancer specific and relapse free survival were also reduced in EN2 positive cases in both univariate and multivariate analyses (multivariate analysis hazard ratios 2.00, 95% CI 1.21-3.30, p=0.007 and 2.17, 95% CI 1.35-3.49, p=0.001 respectively). Pathological complete response (pCR) rate following RC was inversely related to EN2 status (1 of 39 if EN2 positive vs. 23 of 160 if negative, χ2=4.12, df=1, p=0.04). Conclusions: EN2 protein expression is an independent poor prognostic factor following RC for bladder cancer and correlates with a reduced pCR rate. External validation is ongoing. If validated then EN2 expression might assist patient stratification strategies.
Predictive value of topoisomerase 1 by immunohistochemistry (TOP1 IHC) in patients with metastatic breast cancer receiving irinotecan-based therapy.
Authors: Nicholas J. Robert, Stephen Patrick Anthony, David Arguello, Gayle S. Jameson, Donald W. Northfelt, Mohammad Jahanzeb, Emanuel Petricoin, Mariaelena Pierobon, Bryant Dunetz, Lance A. Liotta, David M. Loesch
Journal: Journal of Clinical Oncology (2016)

1037 Background: There is an unmet need for rapid assays predictive of efficacy for specific chemotherapy agents. In particular, for those patients with metastatic disease that have progressed on prior therapies. Newer multi-omic analysis can be performed on a single biopsy specimen and with rapid turn-around-time allowing greater clinical utility. Methods: 49 patients with measurable metastatic breast cancer (MBC) and with a history of prior treatments were enrolled in a prospective phase II study. Real-time biopsies were evaluated with a multi-omic platform which included TOP1 (1D6 antibody, positive if intensity > = 2+ in at least 30% tumor) measured by IHC. 23 of 49 tumors were TOP1 positive. Each of the 23 patients received an irinotecan based regimen as follows: 11 irinotecan alone, 9 (irinotecan+capecitabine) or (irinotecan+fluorouracil/leucovorin), 2 (irinotecan+trastuzumab) and 1 (irinotecan+exemestane). To determine therapeutics benefit, a predetermined endpoint (developed by Von Hoff, et al. JCO 2010 was used: The ratio of the progression free survival (PFS) of the new regimen divided by the PFS of the prior therapy (GMI) with a ratio of 1.3 or greater indicating improved therapeutic benefit from the new regimen. Results: Among the 23 TOP1 positive patients,13/18 evaluable patients were GMI positive (72%), 5 GMI negative, while 4 were not evaluable and 1 was too early for evaluation. In the subset of patients receiving irinotecan alone, 6/11 patients had a positive GMI (55%). Conclusions: In this prospective phase II study in patients with advanced MBC, measurement of TOP1 predicted clinical benefit as measured by GMI, in 72% of all patients receiving irinotecan based therapy and in 6/11 (55%) patients receiving irinotecan alone. These findings warrant further evaluation of TOP1 IHC in predicting the utility of irinotecan in the treatment of breast cancer. Clinical trial information: NCT01919749.
Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy
Authors: Peidi Liu, Emelie Lassén, Viji Nair, Celine C. Berthier, Miyuki Suguro, Carina Sihlbom, Matthias Kretzler, Christer Betsholtz, Börje Haraldsson, Wenjun Ju, Kerstin Ebefors, Jenny Nyström
Journal: Journal of the American Society of Nephrology (2017)

IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type-specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell-positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell-positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with Z scores derived from the expression profile of mesangial cell-positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell-positive standard gene Z score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.