tbuckley/cabot-search huggingface dataset:
Cancer testicular antigens as a prognostic markers of chronic lymphocytic leukemia.
Authors: Julio C. Chavez, Gelenis Domingo, Samir Dalia, Jason A. Dubovsky, Emmanuel Berchmans, John Joseph Powers, Kendra Lynn Sweet, Robert M. Crescentini, Eduardo M. Sotomayor, Rami S. Komrokji, Javier Pinilla-Ibarz
Journal: Journal of Clinical Oncology (2012)

6575 Background: CLL is the most common leukemia in adults and has a variable course and prognosis. Clinical staging systems and the use of biomarkers such as cytogenetics and the IGVH mutational status remain the gold standard for stratification. Cancer testis antigens (CTAs) expression analyses have shown prognostic impact in other hematological malignancies such as acute leukemias and multiple myeloma. With the analysis of CTAs we aim to discover additional molecular markers that can help us predict the clinical course and outcome in CLL patients. Methods: We analyzed the expression by RT-PCR of 39 known CTAs including members of the MAGE, GAGE, MAD-CT and SSX CTAs families in a group of 59 CLL patients seen at our institution. The Moffitt Cancer Center Total Cancer Care (TCC) database was used to correlated these findings with relevant clinical and molecular markers such as Rai stage, demographic data, initial WBC count, IGVH mutational status, CD38 expression, cytogenetics by FISH analysis and treatment outcomes. Overall survival (OS) and progression free survival (PFS) were calculated using Kaplan Meier curves with a SPSS statistical software Results: Deletion 13q was the most common gene abnormality in 35/59 (59.3%). 29/59 (49.1%) required at least one line of treatment. MAGE family CTAs were present in 53/59 (83.9%), MAD-CT in 24/59 (40.7%), SSX in 14/59 (23.7%) and GAGE in 12/59(20.3%). 35/59 (59.3%) CLL patients expressed 2 or more MAGE family CTAs. No differences were noted in the Rai staging, initial white blood cell count, B symptoms, extranodal disease, presence of CD38, or unmutated IVGH. The OS was not significantly different among all CTAs families with a tendency towards a better OS those expressing the SSX family (p=0.63). Additionally, CLL patients with single expression of MAD-CT1 (p=0.05) and MAGE-B2 (p=0.038) antigens correlated with improved survival. Conclusions: Patients with SSX family have a trend towards improved survival. When analyzed by individual antigen, MAD-CT1 and MAGE-B2 expression was associated with improved survival. Further studies with a larger number of patients are needed to assess the real value of the expression of CTAs in CLL.
P14.104 The outcomes of conservatively observed asymptomatic nonfunctioning pituitary adenomas with optic nerve compression
Authors: K Hwang, Y Kim, C Kim, J Han
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND We investigated the natural history of asymptomatic nonfunctioning pituitary adenomas (NFPAs) abutting on optic nerve. MATERIAL AND METHODS Eighty-three patients with asymptomatic NFPAs with documented optic nerve compression on magnetic resonance imaging (MRI) at the time of detection between 2000 and 2016 were included in this study. Patients were evaluated with a hormone test, visual acuity test, visual field test and MRI at the time of diagnosis, and then, yearly, without any treatment (including surgery and radiation). RESULTS The mean age was 57.7±13.6 (range, 15 - 81) years. The mean follow-up duration was 66.6±39.0 (range, 12 - 184) months. Tumor volume growth ≥ 20% was observed in 64 (77.1%) patients. Ten (12.2%) patients experienced any kind of hormonal dysfunction, and gonadotropin deficiency was the most common type of hormonal deficiency [n=9 (10.8%)]. Visual deterioration quantified by Visual Impairment Scale was seen 27 (32.5%) patients. There was no statistically significant factor for tumor growth or visual aggravation. Fourteen (16.9%) patients eventually underwent tumor resection. From multivariate analysis, the significant predictors for eventual surgical intervention were cavernous sinus invasion (OR=20.95; 95% CI, 2.754–159.3; p=0.003) and last follow-up visual field defect score (OR=1.170; 95% CI, 1.049–1.305; p=0.005). All patients who underwent surgery did not experience any neurologic or endocrinological deficits postoperatively. CONCLUSION The clinical outcomes of conservatively observed NFPAs with optic nerve compression can be acceptable. The decision for surgical intervention should be made by balancing the risk and benefits.
P14.97 High risk of venous thromboembolism in patients with brain metastases from non-small cell lung cancer
Authors: P Mir Seyed Nazari, C Ay, A Steindl, B Gatterbauer, J M Frischer, K Dieckmann, G Widhalm, J A Hainfellner, I Pabinger, M Preusser, A Berghoff
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Venous thromboembolism (VTE) is a common complication in patients with cancer. In general, patients with metastatic disease are at highest risk. Lung cancer belong to those tumor entities with a particularly high risk of VTE, ranging between 3–13.8%. However, little is known about the VTE rate in lung cancer patients with brain metastases. MATERIAL AND METHODS Our study was conducted in the framework of the Vienna Brain Metastasis Registry. Clinical data and VTE events during the course of the disease were recorded via retrospective chart review. In this analysis, non-small cell lung cancer (NSCLC) patients with a resection of brain metastases at the Medical University of Vienna between 2006 and 2010 were included. RESULTS In total, 69 NSCLC patients with brain metastases were analyzed. Overall, 69.6% (48/69) patients had an adenocarcinoma, 13% (9/69) a squamous cell carcinoma, 8.7% (6/69) a large cell carcinoma and 8.7% (6/69) other primary tumor histologies. After cancer diagnosis, 20.3% (14/69) patients developed VTE during the course of the disease. Of those, 85.7% (12/14) thromboembolic events occurred after the diagnosis of brain metastases. CONCLUSION Based on our data, patients with brain metastases from NSCLC have a very high VTE risk. Further investigations are needed in order to identify patients with distinct VTE risk profiles. Patients at high risk might potentially benefit from primary thromboprophylaxis over the high risk of intracerebral bleeding.
From a refugee health centre to Brussels: Pietro Bartolo now has two constituencies
Authors: Marta Paterlini
Journal: BMJ (2019)

For 30 years the Italian doctor Pietro Bartolo has been caring for migrants arriving on Lampedusa, where he grew up in a fishing family. The 22 km<sup>2 </sup>island, an exclusive Italian tourist destination, is closer to the Libyan and Tunisian coasts than to Sicily and has been at the centre of the migrant tragedy in the Mediterranean. In May this year, Bartolo was elected to the European parliament. <b>Marta Paterlini</b> asks him about his life
P01.01 The role of exosome miRNA between tumor cells and microglias during the progression of medulloblastoma
Authors: Q Chang, L Zhu, N Li
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Medulloblastoma (MB) is the most common malignant paediatric brain tumor. Recent studies show that M2 cells were relative more abundant in Shh subtype of MBs compared with other three subtypes. It’s known that M2 cells have close relationship with many tumors’ progression. But if they play any role in the progression of Shh subtype of MB is not yet clear. Many studies demonstrate that exosomes carring miRNAs have close relationship with tumor invasion. The aim of present study is to clarify the role of exosome miRNA between tumor cells and microglias during the progression of Shh subtype of medulloblastoma. MATERIAL AND METHODS Immunofluerescence staining using iNOS and Arg1, which is M1 and M2 specific marker, respectively, was performed in four subtypes of MBs. After coculture of exosomes extracted from Shh subtype of MB cell (DAOY) with microglia cell (BV2), Q-PCR and ELISA assay were done to evaluate the polarization status of the microglia. Transwell and scratch assay were then performed to detect the migration ability of DAOY cell after treatment of exosomes from polirized M2 cells. MiRNA sequencing by Ion Proton technology was then done to analyze the miRNAs expression level between Shh subtype and other subtype of MBs. Transformation assay was used to overexpress and inhibit the expression of these miRNAs respectively to further clarify the role of exosome miRNA in the polarization of BV2 cells. RESULTS M2 cells were observed more abundant than other three subtypes of tumors, supporting that M2 cells play some role in this subtype of MBs. Exosomes of DAOY cells can induce the polarization of M2 cells. The polarized M2 cells can improved the migration and invasion ability of DAOY cell. Dozens of miRNAs were identified with different expression level between Shh subtype of MBs and other subtype of MB cells. Among them, 4 miRNAs were reported to be related with polariztion of M2 in many other lesions. Three of the 4 miRNAs can induce the polarization of M2 in present study. CONCLUSION Our study demonstrated exosome miRNA play a critical role between tumor cells and microglias during the progression of Shh subtype of medulloblastoma.
A multi-center study of the effects of toremifene (TOR) and anastrozole (ANA) on serum lipids and bone metabolism in postmenopausal patients with estrogen receptor (ER) positive breast cancer: Interim report
Authors: S. Mitsuyama, Y. Yanagida, H. Doihara, K. Komaki, M. Kusama, T. Ikeda, M. Kimura, M. Sano, K. Miyauchi
Journal: Journal of Clinical Oncology (2006)

645 Background: We have already reported the data that the antiestrogen TOR has better effects than tamoxifen on serum lipid metabolism (ASCO 2003, Breast Cancer Res. Treat 2004). In this study, we evaluated the time course effects of TOR and ANA on serum lipids profile and bone metabolism in ER positive, postmenopausal breast cancer patients with adjuvant hormone therapy. This is the first study to compare TOR and ANA. Methods: Patients were randomly allocated to a TOR40mg/day group (36 cases) or an ANA1mg/day group (33 cases). Serum lipids were measured at before, and 6 and 12 months after the initiation of administration. Changes in the serum lipids and bone markers were compared. Results: Results of lipids: In the TOR group, total cholesterol (TC), LDL, ApoB and Triglyceride (TG) significantly decreased at 6 and/or 12 months compared with the values before the start of administration (p&lt;0.05). HDL and ApoA1 significantly increased at 6 and 12 months in the TOR group (p&lt;0.0002), but ApoA1 at 12 months also significantly increased in the ANA group (p=0.02). Between the TOR and ANA groups, the changes in the percentage of the values of TC, HDL, LDL, ApoA1 and ApoB were significantly different at 6 and/or 12 months (p&lt;0.05). Results of bone markers: BAP significantly increased in the ANA group (p&lt;0.0001); in contrast, NTx significantly decreased in the TOR group (p&lt;0.0001). Between the TOR and ANA groups, the changes in the percentage of the values of BAP and NTx were significantly different at 6 and 12 months (p&lt;0.005). Conclusions: TOR and ANA have different profiles. These findings indicate that TOR has beneficial effects on both lipids and bone metabolism in postmenopausal patients with breast cancer. No significant financial relationships to disclose.
Effect of race/ethnicity on long-term cytopenias and major infections in adolescent young adult breast cancer survivors.
Authors: Candice Sauder, Melanie Goldfarb, Alicia Gingrich, Qian Li, Theodore Wun, Theresa Keegan
Journal: Journal of Clinical Oncology (2019)

11568 Background: Many Adolescent and Young Adult (AYA) Breast Cancer (BC) patients receive chemotherapy as part of their initial treatment. Long-term bone marrow suppression is a potential complication, but no studies have evaluated the impact of race/ethnicity on the development in AYA BC survivors. Methods: Female patients ages 15-39 diagnosed with BC during 1996-2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to statewide hospitalization data. We estimated the cumulative incidence of developing anemia, leukopenia, or major infection/sepsis (≥ 2 years after diagnosis), accounting for death as a competing risk, and examined the impact of race/ethnicity using multivariable Cox proportional hazards regression. Results: Of 14,729 patients, 48.8% were non-Hispanic white, 8.3% non-Hispanic black, 25.5% Hispanic, and 16.5% Asian/Pacific Islander. At diagnosis, 95.5% had local or regional disease (27.7% stage I, 49.4% stage II), and were mostly treated with surgery (96.2%) and chemotherapy (74.3%). The 10-year cumulative incidence of anemia (16.8% vs 11.7%), leukopenia (4.6% vs 2.1%), and major infection/sepsis (13.2% vs 7.9%) was greater following initial treatment with chemotherapy (p &lt; 0.0001 for all vs no chemotherapy). In multivariable analyses controlling for sociodemographic factors, baseline comorbidities, treatment and stage, Blacks had the highest risk (vs. non-Hispanic whites) of medical late effects, including anemia [HR: 1.62, CI 1.41-1.86], leukopenia (HR: 1.53, CI 1.17-2.00), and major infection/sepsis (HR: 1.36, CI 1.16-1.60). Similarly, Hispanic and Asian/Pacific Islanders had a higher risk of developing anemia (HR: 1.16, CI 1.04-1.29; HR: 1.17, CI 1.03-1.33) and trended toward developing more leukopenia (HR: 1.24, CI 1.00-1.54; HR: 1.25, CI 0.98-1.61). Conclusions: AYAs of Black, Hispanic, and Asian/Pacific Islander race/ethnicity are at an increased risk of anemia and leukopenia after chemotherapy compared with non-Hispanic Whites. With improvements in prognostic testing resulting in potential decreased chemotherapy usage, there may be a decrease in long-term late effects for these young cancer survivors.
Association of plasma EGFR mutations with response to first-line chemotherapy and prognosis in Chinese patients with advanced non-small cell lung cancer
Authors: M. N. Wu, J. Zhao, H. Bai, M. L. Zhuo, S. H. Wang, L. Yang, T. T. An, X. Wang, J. C. Duan, Y. Y. Wang, J. Wang
Journal: Journal of Clinical Oncology (2009)

e19017 Background: To investigate associations of plasma EGFR mutations of advanced non-small cell lung cancer (NSCLC) patients with response to the first-line chemotherapy and prognosis. Methods: Plasma EGFR mutations from 145 chemotherapy-naive patients with advanced or metastatic NSCLC were examined by using denaturing high- performance liquid chromatography (DHPLC), and associations of EGFR mutations with tumor response to chemotherapy and clinical outcomes were evaluated. Results: 37.2% (54/145) of the patients was detected to have EGFR mutations in their plasma DNA. The response rate of mutated EGFR carriers to the chemotherapy was 37% (20/54), similar to that of 31.9% (29/91) of wild-type EGFR carriers to the chemotherapy (P= 0.323). Stage IV NSCLC patients with mutated EGFR had a longer PFS than those with wild-type EGFR (4 vs 3 months, P=0.043) after the first-line chemotherapy. The median survival time and 1-, 2- year survival rate for the patients with EGFR mutations (24 months and 85.7%,43.7%) were increased than those with wild-type EGFR (18 months and 65.7%,25.9%) (p=0.0468). Cox multivariate regression analysis showed that clinical stage (IV vs IIIb), response to the first-line chemotherapy (PR vs PD), and EGFR mutations were independent prognostic factors (P=0.008, 0.000 and 0.000 respectively). Conclusions: We conclude that plasma EGFR mutations in the Chinese patients with advanced NSCLC were not associated with response to the first-line chemotherapy, but Stage IV NSCLC patients with mutated EGFR had a longer PFS after the chemotherapy. No significant financial relationships to disclose.
Till death do us part: Existential loneliness (EL), psychosocial distress, and survival of advanced cancer patients (ACPs), and their spousal caregivers (SCs).
Authors: Fay J. Hlubocky, Tamara Sher, David Cella, Mark J. Ratain, Christopher Daugherty
Journal: Journal of Clinical Oncology (2019)

11628 Background: Terminally-ill ACP often experience existential suffering as they near the end-of-life. However, the specific impact of EL on ACP and SC psychosocial wellness and survival has yet to be identified. Methods: A prospective ACP cohort enrolled in phase I trials was assessed at baseline (T1) and at one month (T2) utilizing psychosocial measures: state/trait anxiety (STAI-S/T), depression (CES-D), quality of life/QOL (FACIT-Pal), and global health (SF-36). Semi-structured interviews evaluated the ACP-SC EL experience: cognitive awareness (e.g. death, terminal prognosis); and, emotions (physical isolation; emptiness; abandonment). Results: To date, 160 participants (80 Phase I ACP and 80 SC) have been separately interviewed at T1 and T2. Total population demographics include: median age 62 (28-78y); 50% male; 100% married; 89% Ca; 68% &gt; HS educ; 58% GI dx; ACP median survival 8.3 months (.51-18.9) 55% income &lt; $65,000 yr. At T1, 77% of ACP acknowledged a cognitive awareness of death, 72% reported physical isolation; 54% felt emotional emptiness. For SC at T1, 65% recognized a cognitive awareness of death; 89% felt isolated; and 82% sensed emotional abandonment. Over time, rates of EL remained consistent for ACP-SC with the exception of increased self-reported isolation at 79% and 92% respectively at T2. At T2, ACP with death cognitions had higher STAI-S (32±10 v. 30±11, p = 0.03) and CES-D scores (13±12 v. 11±10, p = 0.02). SC with self-reported abandonment had higher STAI-S anxiety (39±17 v. 35±13, p = 0.03) at T2. Regression analyses revealed ACP with EL death cognitions had poorer FACIT-Pal QOL over time. Moreover, SC with self-reported physical isolation at T2 was negatively associated with SF-36 scores. ACP with EL had shorter overall survival compared to ACP without EL (4.1 v. 6.9 months, p = 0.02). ACP and SC qualitative inquiry re EL exposed unique themes: difficulty articulating EL experience; acceptance of death; finding meaning within crisis. Conclusions: EL is negatively associated with QOL for ACP participating in Phase I trials. Supportive couples-based, dyadic psychological interventions at the end-of-life to assist with coping are warranted.
Challenges in assessing the clinical utility and economic value of immune checkpoint inhibitor therapies of Cancer
Authors: Peter Paul Yu, Omar Eton, Louis P. Garrison
Journal: Journal for ImmunoTherapy of Cancer (2019)

Advances in the immunotherapy of cancer have prolonged survival for cancer patients, but the clinical and financial impact of treatments must be considered in determining the overall clinical utility and economic value of therapeutic agents. Quality-adjusted life years and incremental cost-effectiveness ratios are clinical and economic metrics that can be used to evaluate the value of immune checkpoint inhibitors. This Commentary provides perspective on the limitations, benefits, and potential enhancement of this approach to support value-based medicine.
The SINE Compound KPT-350 Blocks Dystrophic Pathologies in DMD Zebrafish and Mice
Authors: Rylie M. Hightower, Andrea L. Reid, Devin E. Gibbs, Yimin Wang, Jeffrey J. Widrick, Louis M. Kunkel, Jenna M. Kastenschmidt, S. Armando Villalta, Thomas van Groen, Hua Chang, Savanna Gornisiewicz, Yosef Landesman, Sharon Tamir, Matthew S. Alexander
Journal: Molecular Therapy (2019)

Duchenne muscular dystrophy (DMD) is an X-linked muscle wasting disease that is caused by the loss of functional dystrophin protein in cardiac and skeletal muscles. DMD patient muscles become weakened, leading to eventual myofiber breakdown and replacement with fibrotic and adipose tissues. Inflammation drives the pathogenic processes through releasing inflammatory cytokines and other factors that promote skeletal muscle degeneration and contributing to the loss of motor function. Selective inhibitors of nuclear export (SINEs) are a class of compounds that function by inhibiting the nuclear export protein exportin 1 (XPO1). The XPO1 protein is an important regulator of key inflammatory and neurological factors that drive inflammation and neurotoxicity in various neurological and neuromuscular diseases. Here, we demonstrate that SINE compound KPT-350 can ameliorate dystrophic-associated pathologies in the muscles of DMD models of zebrafish and mice. Thus, SINE compounds are a promising novel strategy for blocking dystrophic symptoms and could be used in combinatorial treatments for DMD.
P14.127 From next generation sequencing and comparative genomic hybridization to personalised medicine for adult primary brain tumors: the profiler trial
Authors: A Bonneville-levard, D Frappaz, D Pissaloux, Q Wang, D Perol, J Blay, D Meyronet
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Personalized anti-tumoral therapies may currently be proposed on the basis of immuno-histochemistry, but also next-generation sequencing and comparative genomic hybridization. ProfiLER trial explored the feasibility, efficacy and the impact of molecular profiling for patients with solid or hematological advanced cancers including brain tumors. MATERIAL AND METHODS Patients with primary brain tumors, pre-treated with at least one line of anti-cancer treatment, could be included in this multicentric prospective trial. A molecular profile (next-generation sequencing and comparative genomic hydridization) was established on fresh or archived sample. Weekly molecular tumor board analysed results to propose as far as possible a molecular targeted therapy. RESULTS between February 2013 and December 2015, 141 patients with primary brain tumor were enrolled. One hundred five samples were further analyzed as 30 samples were excluded, and 6 are on-going. The rate of screen failure was 16/33 for stereotactic biopsy (49%) versus 11/104 (11%) for removal. The main representative histologic type of tumors were glioblastoma (n=46, 43,8%), low grade glioma (n=26, 24,8%), high grade glioma (n=12, 11,4%) and atypical and anaplastic meningioma (n=8, 7,6%). Median delay between the diagnostic of the primitive tumor and the inclusion in ProfiLER study was 2.7 years (0.2 - 29 years). Median delay between the consent and the results of the multidisciplinary meeting was 2.8 months (1–7.1 months). Forty-three patients (41%) presented at least one “druggable molecular alteration”. The most frequently altered genes were CDKN2A (n=18, 29%), EGFR (n=12, 20%), PDGFRa (n=8, 13%), PTEN (n=8, 13%), CDK4 (n=7, 11%), KIT (n=6, 10%), PIK3CA (n=5, 8%), MDM2 (n=3, 5%). Sixteen patients could not have a proposition of specific treatment due to death before MBT (n=5, 31.3%), lack of available clinical trials (n=9, 56%), or ambiguous results (n=2, 12.5%). Among the 27 patients (26%) for whom a specific therapy has been proposed, only six patients ultimately received a medical targeted therapy (everolimus n=3, erlotinib n=1, ruloxitinib n=1, sorafenib n=1). Four patients discontinued the treatment for toxicity, the 2 others for clinical progression. CONCLUSION routine high-throughput sequencing is feasible for brain tumors but delays should be reduced to be able to propose targeted therapies to patients fit enough to benefit from experimental treatment. Macroscopic surgery is the best way to obtain workable samples. Specific panel genes for neurologic tumors should be developed, as well as change of practices concerning exclusion criteria in clinical trials.
A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation
Authors: Tuan M. Tran, Rajan Guha, Silvia Portugal, Jeff Skinner, Aissata Ongoiba, Jyoti Bhardwaj, Marcus Jones, Jacqueline Moebius, Pratap Venepally, Safiatou Doumbo, Elizabeth A. DeRiso, Shanping Li, Kamalakannan Vijayan, Sarah L. Anzick, Geoffrey T. Hart, Elise M. O’Connell, Ogobara K. Doumbo, Alexis Kaushansky, Galit Alter, Phillip L. Felgner, Hernan Lorenzi, Kassoum Kayentao, Boubacar Traore, Ewen F. Kirkness, Peter D. Crompton
Journal: Immunity (2019)