tbuckley/cabot-search huggingface dataset:
Impact of environmental tobacco smoke (ETS) on ALK rearrangements in never smokers (NS) with non-small cell lung cancer (NSCLC): Analyses on a prospective multinational ETS registry.
Authors: Akihito Kubo, Masahiko Ando, Ross A. Soo, Tomoya Kawaguchi, Sai-Hong Ignatius Ou, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2013)

7565 Background: EGFR and ALK are important driver mutations in NS. While we reported the significant association of increased ETS with EGFR mutations in Japanese cohort (Kawaguchi, Clin Cancer Res, 2011), ETS association with ALK has not been reported. Methods: ETS exposure on NS with NSCLC was evaluated using the standardized questionnaire including exposure period, place, and duration. Cumulative dose of ETS (CETS) was defined as a sum of the number of the exposure years in childhood and in adulthood, and was treated as a continuous variable or quintile. EGFR mutations and ALK rearrangements were tested by PCR-based detection and fluorescence in situ hybridization, respectively. Multivariate analyses were done using the generalized linear mixed model (GLIMMIX procedure, SAS v9.3). Results: From March 2008 to December 2012, 498 NS with NSCLC were registered with the following patient characteristics: ethnicity (nationality) of Asian/ Caucasian/ others, 425 (Japanese 250, Korean 102, Chinese 46, others 2)/ 48/ 25; male/female, 114/384; age &lt;65/&gt;=65, 286/212. EGFR status was wild type 43.6%, exon 19 deletion 25.3%, L858R 21.5% and other mutations 9.6%. ALK status was wild type 52.0%, rearranged 10.6% and unknown 37.3%. Average CETS (years) of NS with EGFR (+), ALK (+) and wild type tumors were 45.4, 26.9 and 37.7, respectively. In multivariate generalized linear mixed model, incidence of activating EGFR mutations, not ALK rearrangements, was significantly associated with the increment of CETS in female, not in male gender. Odds ratios (OR) for EGFR mutations in female (n=384) were 1.084 (95% CI, 1.003-1.171; p=0.0422) for each increment of 10 years in CETS while OR in male (n=114) were not significant (OR 0.890; 95% CI, 0.725-1.093; p=0.2627). OR for ALK rearrangements in female (n=238) and those in male gender (n=74) were 0.930 (0.791-1.094; p=0.3814) and 0.854 (0.620-1.178; p=0.3319). Conclusions: Increased ETS exposure was closely associated with EGFR mutations in NS with female gender and NSCLC in the expanded multinational cohort. However, the association of ETS and ALK rearrangements in NS with NSCLC was not significant.
A systematic assessment of current genome-scale metabolic reconstruction tools
Authors: Sebastián N. Mendoza, Brett G. Olivier, Douwe Molenaar, Bas Teusink
Journal: Genome biology (2019)

Several genome-scale metabolic reconstruction software platforms have been developed and are being continuously updated. These tools have been widely applied to reconstruct metabolic models for hundreds of microorganisms ranging from important human pathogens to species of industrial relevance. However, these platforms, as yet, have not been systematically evaluated with respect to software quality, best potential uses and intrinsic capacity to generate high-quality, genome-scale metabolic models. It is therefore unclear for potential users which tool best fits the purpose of their research.
Effective Use of Ambulatory Blood Pressure Monitoring
Authors: Philip Greenland
Journal: JAMA (2019)

Wen-Yi Yang, MD, PhD; Jesus D. Melgarejo, MD; Lutgarde Thijs, MSc; Zhen-Yu Zhang, MD, PhD; José Boggia, MD, PhD; Fang-Fei Wei, MD, PhD; Tine W. Hansen, MD, PhD; Kei Asayama, MD, PhD; Takayoshi Ohkubo, MD, PhD; Jørgen Jeppesen, MD, PhD; Eamon Dolan, MD, PhD; Katarzyna Stolarz-Skrzypek, MD, PhD; Sofia Malyutina, MD, PhD; Edoardo Casiglia, MD, PhD; Lars Lind, MD, PhD; Jan Filipovský, MD, PhD; Gladys E. Maestre, MD, PhD; Yan Li, MD, PhD; Ji-Guang Wang, MD, PhD; Yutaka Imai, MD, PhD; Kalina Kawecka-Jaszcz, MD, PhD; Edgardo Sandoya, MD, PhD; Krzysztof Narkiewicz, MD, PhD; Eoin O'Brien, MD, PhD; Peter Verhamme, MD, PhD; Jan A. Staessen, MD, PhD; for The International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (IDACO) Investigators
Survival associated with bone metastases and skeletal-related events in breast cancer patients: A population-based cohort study in Denmark (1999 - 2007)
Authors: M. Yong, A. Ø. Jensen, J. B. Jacobsen, M. Nørgaard, J. P. Fryzek, H. T. Sørensen
Journal: Journal of Clinical Oncology (2009)

e22210 Background: Breast cancer (BrCa) is the most commonly diagnosed cancer for women in the industrialized world. Among women who present with metastatic BrCa, more than half will develop bone metastases. Bone metastases increase the risk for skeletal-related events (SREs) defined as radiation to bone, pathologic fractures, spinal cord compression, surgery to bone, or change in antineoplastic therapy to treat bone pain. These complications are associated with an unfavorable prognosis and have a major impact on patients' quality of life. However, data on survival of BrCa patients who experience SREs are lacking. We evaluated survival among BrCa patients without bone metastases, with bone metastases, and with both bone metastases and SREs. Methods: Using Denmark's National Registry of Patients (NRP) database, we conducted a retrospective cohort study in the North and Mid- Jutland Region. Patients with a diagnosis of BrCa from January 1, 1999 through December 31, 2007 were identified using the International Classification of Diseases, 10 th Revision (ICD-10) codes C50.x. SREs after BrCa diagnosis were identified using the ICD-10 code C79.5. Cox proportional-hazards regression was used to estimate the mortality rate ratio (MRR), adjusting for age and comorbidity, to compare survival among three subgroups of BrCa patients: no bone metastases, bone metastases, and bone metastases with SREs. Results: We identified 9,474 BrCa patients from the NRP. Of these, 621 (7%) developed bone metastases and 267 (3%) developed both bone metastases and SREs during the study period. The 5-year mortality rates among BrCa patients without bone metastases, with bone metastases, and with bone metastases and SREs were 50.7 per 1,000 person-years (PYs), 469 per 1,000 PYs, and 712 per 1,000 PYs, respectively. Compared to BrCa patients without bone metastases, the adjusted MRRs among BrCa patients with bone metastases and patients with bone metastases and SREs were 11.6 [95% confidence interval (CI): 10.9 - 13.6] and 18.1 (95% CI: 15.5 - 21.0), respectively. Conclusions: Our results suggest that bone metastases and SREs have a major impact on the overall mortality of BrCa patients in Denmark. [Table: see text]
<sup>13</sup>C-uracil breath test to predict 5-fluorouracil toxicity in gastrointestinal cancer patients.
Authors: Geraldo Felicio Cunha, Luiz de Marco, Luciana Bastos-Rodrigues, Marina Borges Bolina, Flavia Linhares Martins, Gerson Antonio Pianetti, Isabela Costa Cesar, Luiz Gonzaga Coelho
Journal: Journal of Clinical Oncology (2012)

e13008 Background: Up to 30% of patients on 5-fluorouracil (5FU) experience severe toxicity. Dihydropyrimidine-dehydrogenase (DPD) deficiency explains 36-61% of cases. Predicting toxicity is an unmet challenge. Uracil breath test (UraBT) consists of measuring 13 CO 2 in exhaled breath after ingestion of 2- 13 C-uracil to evaluate pyrimidine (and 5FU) catabolism. Methods: We studied 33 gastrointestinal cancer patients previously exposed to 5FU: thirteen had grade 3-4 and 20, grade 0-1 toxicity. Groups were well-balanced regarding: age (median, 57 years); gender (males, 35%); primary (colorectal, 90%); ethnicity (Caucasians, 55%); chemotherapy (Mayo clinic regimen, 75%). Main toxicities were febrile neutropenia, diarrhea and stomatitis. Tests used to evaluate pyrimidine catabolism: (1) sequencing of three exons of DPYD; (2) plasma dihydrouracil/uracil ratio (UH 2 /U); (3) UraBT. We tested the performance of UraBT to discriminate patients who had grade 0-1 toxicity versus grade 3-4 toxicity and patients with and without proven DPD-deficiency. DPD-deficients were defined as having had grade 3-4 toxicity plus either UH 2 /U &lt; 1.8 or deleterious mutation. Results: 4/13 grade 3-4 toxicity patients proved to be DPD-deficient: three had deleterious mutations (IVS14+1G&gt;A in one; SNP 2846A&gt;T in two), and one had low UH 2 /U ratio. Mean delta over baseline in 50 minutes (DOB 50 ) significantly differed between groups. DOB 50 ≤ 161.4 discriminated individuals with grade 3-4 versus grade 0-1 toxicity (sensitivity= 61.5%; specificity= 85%) and DPD-deficient versus non DPD-deficient (sensitivity= 75%; specificity= 85%). Conclusions: UraBT is a non-invasive and easy to perform method with promising accuracy in discriminating individuals with severe toxicity to 5FU, comparing favorably to most tests available to predict 5FU toxicity. [Table: see text]
Phase II trial of neoadjuvant chemotherapy for HPV-associated squamous cell carcinoma of the oropharynx followed by reduced-dose radiotherapy/chemoradiotherapy for responders or standard dose chemoradiotherapy for nonresponders.
Authors: Bhoomi Mehrotra, David L. Schwartz, Douglas Frank, Benjamin Saltman, Rajasree Roy, Yehuda Z. Lebowicz, Steven R. Savona
Journal: Journal of Clinical Oncology (2012)

TPS5601 Background: Recent studies have established an improved outcome for HPV associated oropharyngeal squamous cell cancers with 3 year OS rates approaching 90%. Given that current aggressive treatment modalities for HNC include IMRT and chemotherapy (CT), they adversely affect the long term QOL of these patients who are considered highly curable. The primary objective of our study is to confirm the activity (CR + PR at 3 months post completion RT/CRT) of induction TPF followed by dose reduced IMRT +/- concurrent CT, in nonsmokers with HPV associated, locally advanced SCC of H&amp;N. Secondary objectives include: to define objective tumor RR to induction chemotherapy and to subsequent RT based treatment, per RECIST version 1.1 criteria, assess PFS and OS at 2 years,assess locoregional disease and distant disease control at 2 years, and monitoring of QOL instruments for HNC. Methods: Institutional IRB approval has been obtained for this study. Eligibility criteria include p16 expressing or ISH + SCC of the oropharynx, T1-3, N1-2, age &gt; 17 years, adequate marrow and organ function and adequate PS. Exclusion criteria include T4 or N3 disease, significant smoking history &gt; 10 pack year lifetime exposure. Patients would be treated with standard TPF induction for 3 cycles followed by risk assessment. Pts. achieving locoregional CR or CR/PR at primary site would receive dose reduced RT (66 Gy) +/- CT, while those with SD/PD would receive standard CRT with full dose XRT. Post therapy assessments include serial evaluation of functional quality-of-life, including M. D. Anderson Dysphagia Inventory (MDADI) and Oropharyngeal swallowing efficiency (OPSE) measures of swallowing function, treatment related symptoms, dietary status assessments and formal sialometric measurement of parotid function. Interim analysis would include RR assessment at 3 months post treatment in the first 12 patients who received dose reduced RT and compared with historical controls. Early stopping rules are built into the protocol. This study is currently open and patient accrual is ongoing.
Abstract 17559: Endothelial Shear Stress Magnitude and Circumferential Heterogeneity Predict the Localization of Eccentric Coronary Atherosclerotic Plaques in Humans
Authors: Michail I Papafaklis, Saeko Takahashi, Antonios P Antoniadis, Ahmet U Coskun, Masaya Tsuda, Yoshiya Orita, Yusuke Fujino, Yasuhiro Makita, Shigeru Nakamura, Shigeru Saito, Charles L Feldman, Peter H Stone
Journal: Circulation (2012)

Introduction: Lesion eccentricity is associated with plaque vulnerability leading to acute coronary events. Endothelial shear stress (ESS) exhibits remarkable heterogeneity over short distances and...
U.S. Preventive Services Task Force (USPSTF) recommendations on PSA screening (PSAS) for prostate cancer (PC): Are they justified?
Authors: Gary M. Strauss
Journal: Journal of Clinical Oncology (2013)

e12535 Background: PSAS has been debated since the Amer Can Soc recommended it in 1992 without data from randomized trials (RTs). Recent RT reports indicate that PSAS does not clearly reduce PC mortality (PCM). In Oct 2011, the USPSTF recommended against PSAS. Does the evidence support this position? Methods: Quebec Trial (QT) randomized 46,193 men 45-80 yrs 2:1 in 1988. Experimental group (EG) was invited for annual PSAS while control group (CG) was not invited. PLCO (Prostate-Lung-Colon-Ovary) randomized 76,693 men 55-74 yrs to annual PSAS or usual care starting in 1993. ERSPC (European study) randomized 162,243 men 55-69 yrs to EG invited to PSAS q4 yrs or CG not invited starting in 1994. Results: QT investigators reported in 1998 that PSAS reduced PCM. The problem was poor compliance with PSAS invitation in QT. Of 30,956 EG, 7,155 (23%) accepted. Of 15,237 CG, 982 (6%) underwent PSAS. Of 8,137 screened (SC), there were 5 PC deaths compared to 137 among 38,056 unSC (RR=0.17; 95% CI: 0.07-0.42). However, this analysis ignores the randomization. Intent to treat (ITT) analysis reveals no PCM reduction (RR=1.11; CI: 0.78-1.59). Selection bias did not account for lower PCM in SC vs unSC. In PLCO, there was no PCM advantage (RR=1.09; CI: 0.87-1.36). However, contamination was high; 72% of CG had PSAS. In ERSPC, there was a reduction in PCM (RR=0.79; CI: 0.69-0.92). Staging of SC detected PC was favorable. In PLCO &amp; ERSPC, increased low/intermediate risk PCs in EGs reflect some overdiagnosis. However, there were significant reductions in high risk or metastatic PC, a hallmark of effective screening. In QT, no pt had distant metastases on repeat PSAS. In PLCO, 10-yr PC survival was ≈94% in both EG &amp; CG. Conclusions: USPSTF recommendations against PSAS are not justified. While PCM comparisons by ITT do not show that PSAS clearly saves lives, ITT analyses are biased due to compliance or contamination. Conversely, RTs demonstrate that PSAS reduces high-risk and metastatic PC. From a population perspective, there has been a dramatic 42% reduction in PCM in US between 1991-2005, largely the result of our "national experiment" in which PSAS was widely introduced. If USPSTF guidelines are implemented, PCM will likely rise in US.
A comprehensive comparison of circulating tumor cell capturing technologies by apheresis of cancer patients.
Authors: Antje Stratmann, Johannes C. Fischer, Dieter Niederacher, Katharina Raba, Arndt Schmitz, Phillip Sangwook Kim, Sharat Singh, Nikolas H. Stoecklein, Thomas Krahn
Journal: Journal of Clinical Oncology (2012)

e21017 Background: Obtaining tumor tissue from cancer patients for diagnosis and biomarker assessment for patient selection is challenging. Circulating tumor cells (CTCs) may represent an attractive alternative as a “liquid biopsy”. However, capturing these rare cells from whole blood is a major challenge that still needs significant improvement. Here we present preliminary data of an ongoing study comparing different CTC capturing technologies. Methods: A collaboration network between Bayer Pharma AG, the University of Düsseldorf as clinical partner and providers of CTC capture methods was established. In addition logistics were organised to guarantee a fast and reliable sample transfer. For optimal comparison, CTC preparations from the same patient were used. The required high amounts of sample aliquots and CTCs was obtained by apheresis. Breast and pancreatic cancer patients (non- and metastatic) were enrolled. Blood samples were obtained, as well as buffy coat by apheresis. Samples were shipped within 48 h to partner companies for CTC analysis. At two sites the CellSearch system by Veridex was performed. Today’s standard was compared with another antigen-based method, a filter method and an approach depending on electrophysiological properties. Downstream analysis of the isolated CTCs was performed at Prometheus using their sensitive immunoassay. Results: Significantly higher CTC amounts were detected in buffy coats obtained by apheresis in comparison with CTC counts obtained from a blood draw. In contrast to the blood samples, all methods were able to detect CTCs in buffy coats from both non-metastatic and metastatic cancer patients. The included novel approaches showed in general a better yield of CTCs in comparison to CellSearch. Downstream analysis revealed individual signalling pathway activity profiles. Conclusions: Apheresis is a suitable procedure to capture high amounts of CTCs and therefore to enable an optimal technology comparison. The isolated CTCs are viable and stimulatable. The preliminary results of our study show that an improvement in CTC capturing is taken place, indicating an important step forward regarding the use of CTCs as “liquid biopsy” in a clinical setting.
Pulmonary blastoma: A clinicopathologic study of three cases.
Authors: Jose D Sandoval-Sus, Damien Mikael Hansra, Maureen Cioffi Lavina, Ravi Patel, Mario Ponce, Edgardo S Santos, Offiong F Ikpatt
Journal: Journal of Clinical Oncology (2013)

e19140 Background: Pulmonary blastoma (PB) is a rare biphasic neoplasm representing 0.2-0.5% of pulmonary malignancies. Presentation ranges from asymptomatic to symptoms of advanced pulmonary tumors. Surgery is the preferred treatment with no consensus on the role of other adjuvant therapies. Methods: We report the clinicopathologic features of PB in 3 patients (pts). Retrospective review of medical records of pts diagnosed with PB at Jackson Memorial Hospital, Miami, FL since 2009. Staging performed using the 2009 AJCC system for NSCLC. Cases required pathological diagnosis before inclusion. Variables analyzed were demographics, clinicopathologic presentation, treatments and outcomes. Results: Mean age at diagnosis was 53 years old; 2 were male; Hispanic and Caucasian and 1 African American female. Both males were heavy smokers. At diagnosis, all cases were symptomatic; 1 had hypercalcemia of 12.9 mg/dL and 2 were stage IV with metastatic disease (bone and thyroid). 2/3 where treated with surgical resection and both achieved complete remission (CR); Pt with stage IV and resection relapsed in 28 months, received chemotherapy (3 cycles cisplatin/docetaxel) with progressive disease then radiation (37 Gy) without response and died. The other surgical patient remains in CR. The patient with unresectable disease received chemotherapy (6 cycles carboplatin/docetaxel) attaining partial remission. 2/3 patients remain alive at end of this study. Pathologically, all cases showed biphasic morphology composed of multiple glandular structures with atypical pseudostratified columnar epithelium and cellular stromal component. Immunohistochemical analysis revealed positivity in all cases for thyroid transcription factor (TTF-1), keratin, and epithelial membrane antigen (EMA) in the glandular component. Conclusions: All pts were symptomatic at diagnosis and 2 presented with metastatic disease. All pts had similar morphologically and immunophenotypically. Surgery was the most beneficial intervention in regard to CR and PFS. Chemotherapy has shown mixed responses, thus, larger studies are needed to define the role of chemotherapy in the adjuvant and palliative settings.
Highly Stable and Long‐Circulating Metal‐Organic Frameworks Nanoprobes for Sensitive Tumor Detection In Vivo
Authors: Ruili Zhang, Chaoqiang Qiao, Qian Jia, Yongdong Wang, Huimin Huang, Wanwan Chang, He Wang, Hao Zhang, Zhongliang Wang
Journal: Advanced Healthcare Materials (2019)

Abstract High stability and extended circulation time in vivo are quite favorable for practical biomedical applications of nanomaterials, because they greatly facilitate the preferential tumor accumulation of nanomaterials, resulting in enhanced signal fidelity for imaging and improved therapeutic effect for treatment. Although many surface modification approaches have been employed to improve the stability and circulating behavior of nanomaterials, it still remains challenging in acquiring stable and long‐lasting nanomaterials for in vivo bioimaging and therapy, especially for nanoscale metal‐organic frameworks (NMOFs) due to their intrinsic instability in physiological conditions. Herein, a facile, one‐step strategy is reported to encapsulate the zirconium (Zr)‐based NMOF UiO‐66 within 1,2‐dioleoyl‐sn‐glycero‐3‐phosphate (DOPA) lipid bilayer (DOPA‐LB). Contrary to UiO‐66 NMOFs functionalized with polyethylene glycol, the obtained UiO‐66@DOPA‐LB presents significantly enhanced stability and impressive blood circulation time, allowing a higher accumulation of UiO‐66@DOPA‐LB in the tumor tissue. Benefited from these meritorious features, UiO‐66@DOPA‐LB labeled with near‐infrared dye, IRDye 800CW, can not only achieve highly sensitive imaging of breast cancer tumor (5 mm), but also exhibits superior capability for early tumor (1–2 mm) detection. This study enriches the surface modification approach of NMOFs, and is of great importance for practical application of NMOFs in biomedical areas.
Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma: CALGB 500104
Authors: T. F. Gajewski, D. Niedzwiecki, J. Johnson, G. Linette, C. Bucher, M. Blaskovich, S. Sebti, F. Haluska
Journal: Journal of Clinical Oncology (2006)

8014 Background: Ras-based signaling is thought to be critical in the genesis of melanoma. Farneslytransferase (FT) inhibitors (FTIs) have been developed as a pharmacologic strategy to inhibit Ras function. Additional farnesylated proteins are also important for the malignant process, and FTIs inhibit melanoma cell line proliferation in vitro. These considerations motivated the development of a phase II trial of the FTI R115777 in patients with melanoma. Farnesylated proteins are also important for T cell activation. The interest in future combinations of targeted agents and immunotherapeutics in this disease prompted analysis of T cell function ex vivo. Methods: A 3-stage design was pursued with a maximum of 40 patients planned and early stopping if there were no responders in the first 14, or fewer than 2 responders in the first 28 patients. Eligibility included intact organ function, PS≤1, no prior chemotherapy, at most 1 prior immunotherapy, no brain metastases, and presence of at least 2 cutaneous lesions amenable to excisional biopsy. R115777 (300 mg orally) was administered twice per day for 21 days of a 28-day cycle. Patients were evaluated every 2 cycles by RECIST criteria. Blood was obtained pre-treatment and during week 7 for analysis of HDJ-2 farnesylation and for T cell IFN-γ production in response to SEA. In addition, tumor biopsies were performed pre- and post-treatment when feasible to directly measure FT activity. Results: 14 patients were enrolled. 2 patients had grade 3 toxicities, which included myelosuppression, nausea/vomiting, elevated BUN, and anorexia. There were no clinical responses, and only 4 patients went on to a second course of treatment. All analyzed patients showed HDJ-2 gel shift in peripheral blood cells, as well as marked inhibition of FT activity (by 85–98%) in tumor tissue. T cell production of IFN-γ was also suppressed. Conclusions: Despite potent target inhibition, the FTI R115777 showed no evidence for clinical activity as a single agent in this cohort of 14 metastatic melanoma patients. Inhibition of T cell function has implications for future combination therapies and suggests the possibility for FTIs as candidate immunosuppressive agents. New therapeutic approaches for melanoma, or logically selected combination therapies, are needed. [Table: see text]