tbuckley/cabot-search huggingface dataset:
PPARγ agonist to inhibit tumor progression by modulating tumor microenvironment.
Authors: Guodong Huang, Xiaowen Sun, Mengqian Li, Limei Yin, You Lu
Journal: Journal of Clinical Oncology (2018)

e24012 Background: Angiogenesis and inflammation are crucial processes, through which the tumor microenvironment (TME) influences tumor growth, invasion and metastasis. PPARγ agonist rosiglitazone has been intensively evaluated as a promising new therapeutic strategy in the treatment of cancer. However, their effect on the TME is unclear. Methods: CCK-8, transwell migration, tube formation assays and western blot were performed to investigate the effects of rosiglitazone on proliferation, migration and angiogenesis in HUVECs. ELISA was performed to examine the effect of rosiglitazone on tumor-derived chemokines CCL2. Each female BALB/c mouse was subcutaneously inoculated with 5×105 murine colon carcinoma cell line CT26 or breast cancer 4T1. When CT26 or 4T1 tumor size approximately reached 50-100 mm3, administration of 100mg/kg rosiglitazone or vehicle was started daily for 2 weeks. Tumors, tumor-draining lymph nodes (TDLNs) and lungs were harvested according to the schedule. Immunofluorescence staining and flow cytometry were performed to investigate the effects of rosiglitazone on normalizing tumor vasculature and TAMs infiltration. H&E staining was used to quantify TDLN and lung metastasis. Results: We found that PPARγ is not only expressed in tumor cells but also in cells of the TME, including tumor endothelial cells and TAMs. Moreover, we presented that rosiglitazone exerts antiangiogenic effects by inhibiting VEGF-VEGFR2 signaling pathways. We also found that rosiglitazone can remodel tumor vasculature contributing to decrease of microvessel density, promotion of pericyte coverage, reduction of CCL2-mediated TAMs infiltration, and even further accompanied improvement of intratumoral hypoxia and vessel perfusion. In addition, 4T1 or CT26 tumor-bearing mice treated with rosiglitazone showed a significant reduction in lesion size, TDLN and lung metastases compared with the control. Conclusions: We provide an evidence that PPARγ agonist rosiglitazone displays effective antineoplastic and anti-metastatic potential. Moreover, rosiglitazone may promote the normalization of the tumor vasculature and limit TAM infiltration, thereby providing a fresh perspective on delaying tumor progression.
Tumor responses and preliminary survival data in a phase II trial of ofranergene obadenovec (VB-111) combined with paclitaxel in patients with recurrent platinum resistant ovarian cancer.
Authors: Richard T. Penson, Suzanne T. Berlin, Ashley M Hanbury, Amalia N Gonzalez, Siobhan A Collins, Michael Birrer, Susana Campos, Ariana Peralta, Andrea R Leubitz, Yael Chava Cohen
Journal: Journal of Clinical Oncology (2016)

5551 Background: Ofranergene obadenovec (VB-111) is a gene therapeutic consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a Fas-chimera transgene in angiogenic endothelial cells. Over 170 patients have been treated with VB-111 across different cancer indications with evidence of anti-tumor activity with no significant safety issues. We report results of the phase II study of VB-111 in combination with paclitaxel in patients with recurrent müllerian cancers. Methods: VB-111 was administered as intravenous infusion at escalating doses from 3x1012 (DL1&2) to 1x1013 viral particles (VPs) (DL3, therapeutic dose) every 2 months. Paclitaxel was given at 40 mg/m2 (DL1), and 80mg/m2 weekly (DL2-3). A phase 2 expansion cohort commenced at DL3 (therapeutic dose). Assessments included safety, tumor response (CA-125 and RECIST), histopathology, progression free survival (PFS) and overall survival (OS). Results: Nineteen patients at 2 US centers received up to 7 repeat doses of VB-111, 15/19 received the therapeutic dose. Median age was 65 (41-79) with a median of 3 prior lines of therapy. No DLTs were observed. VB-111 was associated with flu-like symptoms and mild infusion reactions; the drug was safe and well tolerated. In the therapeutic dose cohort, a 60% response rate (RR) was seen by the GCIG criteria (more than 50% reduction in CA-125), 93% had clinical benefit. The median OS was not reached, mean OS was 19.9 months. A dose-response was seen. Within the therapeutic dose cohort (n = 15), responses seen in 3 of the 5 patients who had received prior bevacizumab (RR 60%) and in 5 of the 9 pts with platinum refractory disease or progressive disease within 3 months of platinum (RR 55%). On study biopsies suggest that further to the anti-angiogenic mechanism of action VB-111 induced antitumor immune reaction. Conclusions: VB-111 in combination with weekly paclitaxel was safe and well tolerated in ovarian cancer patients. Anticipated toxicities were observed. Tumor responses were seen and survival data is encouraging. Clinical trial information: NCT01711970.
Prognostic significance of performance status in patients with head and neck squamous cell carcinomas (HNSCC) receiving immune checkpoint monoclonal antibodies (ICmAB) in a single institution.
Authors: Victoria Hwang, Renato G. Martins, Keith D. Eaton, Laura Quan Man Chow, Christina S. Baik, Bernardo H. L. Goulart, Sylvia Mina Lee, Rafael Santana-Davila, Cristina P. Rodriguez
Journal: Journal of Clinical Oncology (2017)

e17506 Background: The anti-PD1/-PDL1 ICmABs can result in objective responses in some (13-20%) patients (pts) with HNSCC. We evaluated clinical factors that may predict oncologic outcomes. Methods: We identified pts who received an ICmAB at our institution and retrospectively collected demographic, tumor, treatment, progression, and survival data. The Kaplan Meier method was used to estimate survival. Log-rank and Wilcoxon tests were used to explore associations between clinical features and outcomes. Results: 55 pts received ICmAB in a clinical trial at our center from 8/2012 to 12/2016. The median age was 64 years, 13 (24%) were female, and 45 (82%) were white. ECOG Performance Status (PS) was 0 and 1 in 23 (42%) and 32 (58%) pts, respectively. 29 (53%) were current/former smokers who smoked a median of 20 (range 0-70) pack years. Primary sites included: oropharynx (OP) 31 (56%), oral cavity 9 (16%), nasopharynx 6 (11%), nasal cavity 3 (5%), hypopharynx (HP) 2 (4%), unknown (UK) 2 (4%), and skin 2 (4%). 28 (51%) were p16+, with the following primary sites: OP in 26, UK in 1, and HP in 1. 53 (96%) received prior curative intent therapy. A median of 2 (range 0-5) lines of systemic therapy (including curative intent) were given prior to ICmAB initiation, and 31 received an ICmAB as a single agent. There were 19 (35%) objective responses with 1 complete response, and 14 (25%) had stable disease. With a median follow-up of 12 months (m), the median overall survival (OS) was 15m (95% CI 11,47), and median time to progression was 4m (95% CI 2.2, 6.8). An ECOG PS of 0 vs 1 was associated with superior OS (36m vs 11m p = 0.001). Tobacco use, p16+ disease, single agent ICmAB vs. combination, number of lines of prior systemic therapy, or radiation therapy within 3m prior to ICmAB initiation did not appear to have a relationship with survival. Conclusions: A PS of 0 predicted for more favorable OS among HNSCC pts receiving ICmAB in this single center retrospective cohort. In contrast to data with chemotherapy, established prognostic markers (including p16+ and limited/no tobacco use) did not appear to impact survival.
Abstract 14267: Comparative Study of Cardiac Magnetic Resonance and Endomyocardial Biopsy to Predict Left Ventricular Reverse Remodeling and Prognosis in Dilated Cardiomyopathy
Authors: Takeru Nabeta, Takayuki Inomata, Yuki Ikeda, Syunsuke Ishii, Takanori Sato, Takashi Naruke, Toshimi Koitabashi, Tohru Izumi, Yusuke Inoue, Junya Ako
Journal: Circulation (2013)

Purpose: Both endomyocardial biopsy (EMB) and late gadolinium enhancement-cardiovascular magnetic resonance (LGE-CMR) imaging are used to evaluate myocardial fibrosis, however, few reports have dir...
TCT-251 Use, safety and effectiveness of Subintimal Angioplasty and Re-entry Devices for the Treatment of Femoropopliteal Chronic Total Occlusions; a Systematic Review of 87 Studies and 4,671 Patients.
Authors: Damianos Kokkinidis, Ioannis Katsaros, Anil Jonnalagadda, Seth Avner, Ehrin Armstrong
Journal: Journal of the American College of Cardiology (2018)
Characterizing the amyloidogenic protein in patients with light chain amyloidosis using mass spectrometry.
Authors: Taxiarchis Kourelis, Mindy C. Kohlhagen, John Mills, David R. Barnidge, Surendra Dasari, Angela Dispenzieri, David L Murray
Journal: Journal of Clinical Oncology (2017)

e19534 Background: Our group has developed a mass spectrometry (MS) method that can identify circulating monoclonal proteins, based on their unique molecular mass signatures. Given the propensity for patients with AL amyloidosis to have MS patterns consistent with post-translational modifications (PTMs), we posed the question whether these changes might be present long before the diagnosis of AL and potentially serve as a predictor for AL in patients with an asymptomatic plasma cell dyscrasia (aPCD). Methods: We included 64 patients with AL who had a preceding aPCD and who had stored serum samples at both time-points. The mass/charge (m/z) of monoclonal LC peaks (P) was noted for each sample. Presence of a PTM was defined as the presence of ≥1 “heavy” Ps at a particular charge state. A P was considered heavy if its m/z exceeded the right sided 95% C.I. of the m/z distribution of the respective normal LC. We used 9 patients with relapsed multiple myeloma (MM) without AL as controls. Results: Prior aPCDs were MGUS (N = 33), smoldering myeloma (n = 9) and MM (N = 1). In 21 patients aPCD was not further classified with a bone marrow biopsy. The median interval between aPCD and AL diagnosis was 77 months. At aPCD diagnosis, 42 patients had a single, typical P and 21 patients (33%) had PTMS: 13 patients had a single heavy P; 5 patients had 2 P (only one of which was heavy); and 3 patients had 2 heavy peaks. No PTMs were noted in our MM controls. The m/z of all typical and heavy P observed at aPCD remained unchanged for 63 patients as they transitioned to AL, which suggests no new PTMs occurred with the exception of one patient, who had a single PTM at aPCD diagnosis, but developed 2 additional heavy P appearing at +1232 and +1392 Dalton at AL diagnosis, suggestive of new PTMs. In all but 3 aPCD, the typical P was more abundant relative to heavy P. Heavy P abundance increased in 6 patients as they transitioned from the aPCD to the AL state and exceeded that of the typical P in 3 patients, suggestive of increasing abundance of existing PTMs in these cases. Conclusions: Pre-existing PTMs are present in 1/3 of AL patients and not in MM and can be used to identify patients at risk for AL. New PTMs are uncommon, but the relative abundance can change over time.
Self-reported financial stress among patients evaluated at a community cancer program.
Authors: Christopher S. Lathan, Ruth N. Akindele, Ludmila Svoboda, Daniel A. Gundersen
Journal: Journal of Clinical Oncology (2017)

6553 Background: Cancer related financial stress has been linked to a multitude of factors including socio-economic status, but its impact on the quality of life (QOL) for underserved populations is less well characterized. We evaluated patient reported financial stress, QOL, and quality of health (QOH) at an outreach cancer program located in a federally qualified health center. Methods: Study participants were interviewed at initial clinic visit for financial stress, QOH and QOL between January 2012 and December 2016. Demographic information, insurance coverage, clinical parameters, and comorbidities were abstracted from participants’ medical records. Responses to the financial stress index question “how difficult is it for you or your family to meet monthly payment of your/your family bills?” and overall QOL and QOH of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 were analyzed. Proportional odds logistic regression models were constructed for 5-point quality of life measures and three levels of financial toxicity. Results: Of the 288 participants analyzed, 52% and 12% reported somewhat and extreme financial stress. In an adjusted analysis, patients who reported financial stress were more likely to be younger in age (OR = 4.03, p &lt; 0.001) unemployed (OR = 3.24, p = 0.002), have less than bachelor’s degree (OR = 0.035, p = 0.018), insured by Medicaid (OR = 3.22, p &lt; 0.011), and were more likely to rate their QOL (OR = 3.76, p = 0.031) as poor, compared to those without financial stress. Race, gender, presence of cancer diagnosis and comorbidities were not associated with financial distress. Independent predictors of poor QOL were disability (OR = 3.12, p = 0.005), depression (OR = 2.12, p = 0.007) and extreme financial difficulty (OR = 2.57, p = 0.011). There was a nearly perfect positive correlation between overall QOL and QOH (r = 0.984, p &lt; 0.001). Conclusions: There is a high prevalence of financial burden among underserved minority patients seeking cancer related care, and this is closely associated with poor quality of life. Interventions targeting cancer disparities need to assess financial stress in order to address this issue.
TCT-71 Predictors, incidence and outcomes of patients undergoing transcatheter aortic valve implantation complicated by stroke – From the CENTER-Collaboration
Authors: Wieneke Vlastra, Pilar Jimenez-Quevedo, Didier Tchetche, Jaya Chandrasekhar, Fabio Brito, Marco Barbanti, Ran Kornowski, Azeem Latib, Augusto D'Onofrio, Flavio Ribichini, Jan Baan, Jan Tijssen, Jose de la Torre Hernandez, Nicolas Dumonteil, Rogério Leite, Samantha Sartori, Paola D'Errigo, Chiara Fraccaro, Mattia Lunardi, Katia Orvin, Matteo Pagnesi, Rosana Hernandez, Thomas Modine, Roxana Mehran, Jan Piek, Ronak Delewi
Journal: Journal of the American College of Cardiology (2018)
mRNA expression of PSCA and ERBB2 in pancreatic ductal adenocarcinoma.
Authors: Hong Ma, Shuguang Huang, Carlos Becerra, Annemarie Moseley
Journal: Journal of Clinical Oncology (2016)

e15709 Background: Prostate stem cell antigen (PSCA) and receptor tyrosine-protein kinase erbB-2 (ERBB2) are tumor associated antigens related to pancreatic ductal adenocarcinoma (PDAC). The objective of this research was to investigate the mRNA expression of PSCA and ERBB2 in PDAC using public datasets. Methods: NBCI GEO microarray datasets that met the following criteria (1) keywords “Pancreatic” and “U133”, (2) has both tumor and normal pancreatic tissues,(3) sample size > 20, were identified. Within each identified dataset, PSCA and ERBB2 mRNA over-expression was defined as the 95th percentile of the mRNA expression in the normal pancreatic tissues. The differential expression between PDAC and normal pancreatic tissues were compared using T test. A Meta-analysis was further conducted to combine the results from the multiple datasets. As a step of further validation, the mRNA expression level found from GEO data was compared to the corresponding findings based on TCGA NGS data. In addition to PSCA and ERBB2, PubMed was searched to identify the list of putative biomarkers for PDAC to support the findings. These genes were evaluated by the same approach. Results: Three GEO datasets with a total of 89 arrays of PDACs and 63 normal pancreatic tissues were identified: GSE15471 (PDAC = 39, normal = 39), GSE16515 (PDAC = 36, normal = 16), GSE17989 (PDAC = 14, normal = 8). We identified a list of additional 25 genes. The results for other markers were not shown except CA19-9 since it is the most common clinical biomarker for PDAC. Meta-analysis showed PSCA, ERBB2 and CA19-9 had significant over-expression in tumors consistently across the three GEO datasets. PSCA was over-expressed in 35%, 50% and 60% of the PDACs while ERBB2 was over-expressed in 25%, 40% and 65% of the PDACs in GSE15471, GSE16515 and GSE17989, respectively. These results were similar to the findings in TCGA data. Among the 145 samples, TCGA showed that PSCA and ERBB2 were over-expressed in 21% and 30% of the PDACs, respectively. Conclusions: The analysis of public microarray data indicated that PSCA and ERRB2 were over-expressed in PDAC. This finding is consistent with published literatures and provides additional evidence that PSCA and ERRB2 are attractive drug targets for PDAC.
Association of Prenatal Exposure to Ambient and Traffic-Related Air Pollution With Newborn Thyroid Function
Authors: Caitlin G. Howe, Sandrah P. Eckel, Rima Habre, Mariam S. Girguis, Lu Gao, Frederick W. Lurmann, Frank D. Gilliland, Carrie V. Breton
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Thyroid hormones are critical for fetal growth and development. Prenatal particulate matter (PM) air pollution exposure has been associated with altered newborn thyroid function, but other air pollutants have not been evaluated, and critical windows of exposure are unknown. <h3>Objectives</h3> To investigate the association of prenatal exposure to ambient and traffic-related air pollutants with newborn thyroid function and identify critical windows of exposure. <h3>Design, Setting, and Participants</h3> This cohort study used data from 2050 participants in the Children's Health Study. Statistical analyses were conducted from 2017 to 2018 using pregnancy and birth data from 1994 to 1997 for a subset of participants recruited from schools in 13 southern California communities in 2002 to 2003 when participants were 5 to 7 years of age. Participants were included in statistical analyses if they could be linked to their newborn blood spot and had complete monthly exposure measures for at least 1 air pollutant across pregnancy. <h3>Exposures</h3> Prenatal monthly averages of ambient (PM diameter &lt;2.5 μm [PM<sub>2.5</sub>] or &lt;10 μm [PM<sub>10</sub>], nitrogen dioxide, and ozone) and traffic-related (freeway, nonfreeway, and total nitrogen oxides) air pollutant exposures were determined using inverse distance-squared weighting of central monitoring data and the California Line Source Dispersion model, respectively. <h3>Main Outcomes and Measures</h3> Newborn heel-stick blood spot total thyroxine (TT4) measures were acquired retrospectively from the California Department of Public Health. <h3>Results</h3> Participants included 2050 newborns (50.5% male), with a median (interquartile range) age of 20 (15-29) hours. The majority of newborns were Hispanic white (1202 [58.6%]) or non-Hispanic white (638 [31.1%]). Sixty-six (3.2%) were black and 144 (7.0%) were from other racial/ethnic groups. The mean (SD) newborn TT4 measure was 16.2 (4.3) μg/dL. A 2-SD increase in prenatal PM<sub>2.5</sub>(16.3 μg/m<sup>3</sup>) and PM<sub>10</sub>(22.2 μg/m<sup>3</sup>) was associated with a 1.2-μg/dL (95% CI, 0.5-1.8 μg/dL) and 1.5-μg/dL (95% CI, 0.9-2.1 μg/dL) higher TT4 measure, respectively, in covariate-adjusted linear regression models. Other pollutants were not consistently associated with newborn TT4. Distributed lag models revealed that PM<sub>2.5</sub>exposure during months 3 to 7 of pregnancy and PM<sub>10</sub>exposure during months 1 to 8 of pregnancy were associated with significantly higher newborn TT4 concentrations (<i>P</i> &lt; .05). <h3>Conclusions and Relevance</h3> Prenatal PM exposure, particularly in early pregnancy and midpregnancy, is associated with higher newborn TT4 concentrations. Future studies should assess the health implications of PM-associated differences in newborn TT4 concentrations.
Missed opportunities: Oncologists and palliative care specialists may be the last chance to explore hereditary cancer among cancer in-patients before information and DNA is lost.
Authors: Mohammed Abusamaan, John Quillin, Oluwafemi Owodunni, In Guk Kang, Brandon Yu, Brittany Ma, Lauren Bailey, A. Rab Razzak, Thomas J. Smith, Joann Bodurtha
Journal: Journal of Clinical Oncology (2018)

e13505 Background: Hereditary cancer assessment and communication about family history risks can be critical for surviving relatives. Oncology and palliative care (PC) are often the last set of providers before death giving a unique window for intervention. Methods: We replicated a prior study (Quillin JM, 2010) of the prevalence of hereditary cancer risk among a semi-consecutive group of cancer patients receiving palliative care (PC) consultations, assessed the recorded history in EPIC, and explored cancer patients’ attitudes toward PC discussions about family history. This prospective study was conducted at an academic urban hospital and cancer center between June 2016 and March 2017, collecting data through structured interviews and chart review. Results: Seventy-five adult cancer patients enrolled, average age 60, 49 (55%) male and 49 (65%) white. Nineteen patients (25%) had no clear documentation of family history in EPIC; sometimes because no family history was included in in the admission template (e.g. surgery), or a history had been automatically imported but lacked content. Twenty-four patients (32%) were considered to have high risk pedigrees that merited referral to genetic services. Forty-eight patients (64%) thought that palliative care was an appropriate venue to discuss the implications of family history. The mean comfort level in addressing these questions was high at 8.7 on a 10-point scale. Conclusions: At a large academic center, 25% of patients had no family history documented in the EMR. 32% of pedigrees warranted referral to genetic services, which was rarely documented. There is substantial room for quality improvement for oncologists and palliative care specialists – often the last set of providers – to address family cancer risk before death, and to increase use and ease of documenting family history in the EMR. Addressing cancer family history could enhance prevention, especially among high-risk families.