tbuckley/cabot-search huggingface dataset:
Preliminary safety and outcome report of the metronomic therapy from the Latin American osteosarcoma treatment protocol 2006.
Authors: A. S. Petrilli, C. R. Macedo, S. R. C. Toledo, P. C. Pavoni-Ferreira, M. Grings, M. Scopinaro, S. Ferman, E. Boldrini, M. T. A. Almeida, C. T. de Oliveira, G. L. Rey, L. A. Castillo, M. L. Borsato, J. H. Barreto, V. L. L. Morais, A. L. Brunetto, D. Lustosa
Journal: Journal of Clinical Oncology (2011)

10032 Background: Based on results from leukemia maintenance therapy, anti-angiogenic approaches have been indicated as alternatives for solid tumors. In this rationale, metronomic therapy (MT) emerged as a low toxicity, low cost, oral treatment aiming to increase survival. Methods: 429 high-grade extremity osteosarcoma patients were enrolled in this study. Standard therapy consists of cysplatin, doxorubicin and HDMTX. Non-metastatic patients (NMP) are randomized at the end of MTD treatment (week 31) for no treatment (arm A) or MT until week 104 (arm B). All metastatic patients (MP) are assigned to MT concomitant with MTD treatment until week 104. 92 patients (26 MP and 66 NMP) were excluded as they did not receive MT or were not randomized. There is data from 242 patients in the group database. 91 MP and 72 arm B NMP received MT: CTX 25mg/m2/day everyday and MTX 3mg/m2/day twice a week. Dosage modifications were allowed to keep WBC count <3500/mm3 or due to grade 3/4 toxicities. Adherence to treatment was self-reported and recorded on patient charts. In this study, one cycle of MT was 28 days. Circulating and tumoral THBS1, VEGFA, PDGFC, FLT1, KBR, CXCL12 and CXCR4 protein and gene expression are being investigated to evaluate angiogenic activity and identify possible angiogenic markers. Results: The main toxicity found during MT alone was anemia grade I in 27% of the cycles. Neutropenia grades 3/4 was found on 3.5% of the cycles. In around 72% of the cycles, a dosage increase was needed due to high WBC counts. 88% of arm B NMP remain alive with median follow-up time of 23 months (versus 89% of patients not randomized to MT). Relapse was seen on 16% of the cases (versus 18%). 79% of MP remain alive with median follow-up time of 23 months (versus 57% of patients that did not receive MT). Conclusions: MT is well tolerated with no grade 3/4 non-hematological toxicities when used alone and did not increase toxicities if used concomitantly with MTD chemotherapy. The number of patients and short follow-up period restricts the outcome analysis but it seems that metronomic therapy may play an important role on avoiding disease progression for metastatic patients while its role on avoiding relapse needs further evaluation.
Who provides ongoing care to breast cancer survivors and does it make a difference?
Authors: M. Sowden, T. B. Sanft, A. B. Chagpar
Journal: Journal of Clinical Oncology (2011)

199 Background: There is a paucity of data regarding who provides ongoing care for breast cancer survivors, and the impact of this on adherence to screening guidelines. The purpose of this study was to define, in a population based cohort, with whom breast cancer survivors receive their ongoing care and the impact of provider choice on quality of care. Methods: Data from the 2005 National Health Interview Survey were queried for provider types and screening adherence in breast cancer survivors. Statistical analyses were performed using SAS and SUDAAN software. Results: 435 breast cancer survivors were surveyed in 2005. Their mean age was 66, and the median age at diagnosis was 57. 284 (60.9%) were more than 5 yrs out from diagnosis. Of respondents, 84.3% reported having a clinical breast exam (CBE) within the past year and 79.8% reported having had a mammogram (MMG) within the past 2 years. 429 (99%) reported whether they had seen a family physician (GP) and/or OBGYN in the preceding 12 months; specific reference to care by oncologist was unavailable. 91.8% of survivors had seen either their GP and/or OBGYN in the last year. No significant differences were seen in provider choice nor adherence to surveillance recommendations based on survivorship period (≥ or &lt; 5 yrs). There was no significant difference in CBE and MMG between survivors who had seen their GP within the preceding 12 months and those who did not, but those who had seen their OBGYN had a significantly higher rate of having had a CBE (92.0% vs. 81.1%, p=0.01) and MMG (90.1% vs. 75.3%, p&lt;0.01) than those who did not. Adherence to screening recommendations was superior for patients who had been seen by multiple providers than those who had not been seen by any. Conclusions: Breast cancer survivors get their follow-up care through a variety of providers, often relying on primary care. A collaborative survivorship plan involving multiple specialties may improve adherence to screening guidelines. [Table: see text]
Candidate biomarkers in renal cell carcinoma.
Authors: B. Seliger, R. Lichtenfels, C. Recktenwald, S. Dressler, D. Atkins, S. Stevanovic
Journal: Journal of Clinical Oncology (2011)

405 Background: Renal cell carcinoma (RCC) represents a heterogeneous disease with widely varying prognosis. Therefore, the screening for biomarkers, which allow the diagnosis as well as the assessment of the individual risk of disease progression and mortality are a prerequisite for the selection of patients for different modes of therapies and the implementation of individually tailored surveillance protocols. Methods: Various proteome-based technologies such as 2DE-based proteomics, PROTEOMEX or ligandomics in combination with mass spectrometry have been applied. Bioinformatic data mining led to the categorization and priorization of the respective target lists. Selected candidate targets were further independently verified by qRT-PCR, Western blot and/or immunohistochemistry. Results: A large series of differentially expressed/immunoreactive proteins have been identified in clear cell RCC when compared to normal kidney epithelium. With the different approaches distinct sets of potential candidate targets were defined and categorized into different protein families and functions and according to their cellular localization. Moreover, the limited sharing rates between the respective target lists demonstrate their complementarity. Some selected markers were further validated by qRT-PCR, Western blot analysis and/or immunohistochemical stainings of tissue micro arrays comprised of RCC lesions of different TNM classification and histology revealing distinct expression pattern in regard to the RCC subtype, tumor grading,staging or additional molecular features. Using the ligandomics approach proteins have been identified, which were able to mount an immune response in vitro. Conclusions: Some candidate markers might have the potential to be used as diagnostic and prognostic factors if not as novel targets for therapy and thus could be employed for the expression profiling of a larger series of RCC patients. No significant financial relationships to disclose.
A clinical and serological study of linear IgA bullous dermatosis without linear immunoglobulin deposition other than IgA at the basement membrane zone using direct immunofluorescence
Authors: C. Ohata, N. Ishii, H. Koga, T. Nakama
Journal: British Journal of Dermatology (2016)

Linear IgA bullous dermatosis (LABD) is a heterogeneous disease. Different diagnostic criteria have been used in different reports.To reappraise the characteristic features of LABD with only IgA deposition at the basement membrane zone (BMZ) with direct immunofluorescence (DIF).We retrospectively collected data from 101 patients from our archival records from 1 January 1996 to 31 December 2014 who had: (i) blisters on the skin and/or mucous membranes; (ii) subepidermal blisters in a biopsy specimen; and (iii) linear IgA deposition along the BMZ with/without linear C3 deposition at the BMZ with DIF. Most patients were referred for serological evaluation. Patients who showed concurrent linear IgG and/or IgM deposition at the BMZ under DIF were excluded. Clinical manifestations and serological findings were analysed.Heterogeneity of autoantigens in LABD was confirmed. Fifty-four of 101 patients (53%) had IgG antibodies detected either by indirect immunofluorescence, immunoblotting or enzyme-linked immunosorbent assays (ELISA). No statistical difference in clinical manifestations was found between patients in the IgG antibody-possessing group and patients in the other group.An association of IgG anti-BMZ antibodies with LABD may increase if new IgG immunoblotting or ELISA techniques become available. Consensus for diagnostic criteria for LABD is desired for prospective data storage, although it may be arbitrary.
Efficacy of weekly paclitaxel in patients with advanced gastric cancer with prior docetaxel-containing chemotherapy.
Authors: Takayuki Ando, Ayumu Hosokawa, Kohei Ogawa, Shinya Kajiura, Yuko Itaya, Akira Ueda, Yuji Tsukioka, Takashi Kobayashi, Naoki Horikawa, Toshiro Sugiyama
Journal: Journal of Clinical Oncology (2012)

127 Background: Efficacy of paclitaxel for docetaxel-refractory gastric cancer is not known, although partial cross-resistance between docetaxel and paclitaxel has been demonstrated in breast and ovary cancers. Therefore, we retrospectively evaluated the efficacy of paclitaxel in gastric cancer patients who had been refractory to docetaxel-containing chemotherapy. Methods: The patients who had received docetaxel-containing regimen were categorized as prior-docetaxel group, and the patients who had never received docetaxel were categorized as non-docetaxel group. Paclitaxel at 80 mg/m 2 was administered by intravenous infusion in all patients, and this was repeated weekly for 3 weeks out of 4. The response rate (RR), median progression-free survival (PFS) and overall survival (OS) were evaluated in two groups. Results: 65 patients were included between April 2006 and June 2011. Among them, 26 patients were prior-docetaxel group, and 39 patients were non-docetaxel group. The median age, gender, performance status, histology, history of gastrectomy, metastatic site, and the number of metastatic sites were not statistically different between two groups. In prior-docetaxel group, the RR was 14.2% (3/21) among the patients with measurable lesions, the median PFS was 79 days (95%CI, 47-135 days), and the OS was 123 days (95% CI, 90-215 days) from the initiation of paclitaxel administration. In non-docetaxel group, the RR was 11.5% (3/26) among the patients with measurable lesions, the PFS was 82 days (95% CI, 52-106 days), and the OS was 143 days (95% CI, 121-178 days). There were no significant differences in the RR (P = 0.78), PFS (P = 0.98), and OS (P = 0.51) between two groups. Conclusions: Weekly paclitaxel was modestly active in gastric cancer patients who had been refractory to docetaxel containing chemotherapy. This represents that there was incomplete cross-resistance between docetaxel and paclitaxel in gastric cancer chemotherapy, as previously reported in other cancers.
Nitric Oxide As a Mediator of Bone Marrow Fibrosis in Patients with Myelofibrosis
Authors: Ali Tabarroki, Daniel Lindner, Valeria Visconte, Nikolaos Papandantonakis, Jing Ai, Mikkael A. Sekeres, Anjali S. Advani, Matt E. Kalaycio, Tracy Cinalli, Kristin Colaluca, Gina Rupp, John Desamito, Heesun J. Rogers, Ramon V. Tiu
Journal: Blood (2014)
HER2 evaluation in a specific gastric cancer population with the highest rate of mortality in Spain.
Authors: Esther Una Cidon
Journal: Journal of Clinical Oncology (2012)

60 Background: Gastric Cancer (GC) still represents the second cause of cancer-related death worldwide. Radical resection is the mainstay of early stages treatment with few impact in overall survival (OS) in the advanced ones. HER-2 is the most relevant biological factor involved. Purpose: This study aims to show the relationship between HER-2 positivity and survival in patients with completely resected GC. Methods: Retrospective study of GC patients diagnosed in 2003-2005 at our institution. Surgical specimens underwent immunohistochemistry (IHC) and in cases +/++/+++ samples underwent also fluorescence in situ hibridysation (FISH) analyses of HER-2 and graduated according experts consensus. Results: 120 cases included. Overall expression detected in 7.5%. Correlation between HER-2 positive and female sex, advanced stages or histological grades or intestinal type was detected. Early recurrences higher in HER-2 positive (66.6% vs 35.4%, p 0.048). The median DFS for c-erbB-2 positive was 15 months (range 2-67 months) and OS was 25 months (range 10-67 months). In the case of patients with c-erbB-2 negative median DFS was 27 months (range 5-67 months) and OS for this sample is 47 months (range 29-67 months). Conclusions: These results emphasize the relevance of HER-2 positivity in GC as independent prognostic factor and supports its current analyses in daily practice.
Immunologically Targeting the Leukaemia Phosphoproteome
Authors: Hugo De La Peña, Thomas Butler, Hsing-Wen Huang, Toral Jakhira, Chung-Yang Joseph, Sarah Penny, David Millar, Charles Craddock, Guy Pratt, Michael E. Williams, Donald F Hunt, Victor H Engelhard, Mark Cobbold
Journal: Blood (2010)
Use of germ-line single nucleotide polymorphisms (SNPs) in drug transporters (ABCG2/ABCB1) and tubulin (TUBB4) to predict survival in patients with metastatic castrate-resistant prostate cancer (CRPC) receiving docetaxel.
Authors: N. M. Hahn, J. Jung, S. Philips, Y. R. Patel, K. A. Carr, Y. Mohammadi, D. Magjuka, L. Li, C. Sweeney, T. C. Skaar
Journal: Journal of Clinical Oncology (2011)

58 Background: Multiple treatment options now exist for metastatic CRPC patients (pts). Germ-line SNPs in docetaxel (D) transport, metabolism, binding site, and degradation genes may contribute to variability in outcomes observed in D treated CRPC pts. Methods: Between 1/07 and 10/08, all PCa pts seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a blood sample. Only CRPC pts treated with D were included in this analysis. Germ-line DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit (Applied Biosystems). The chip included genes critical to D signaling, transport, and elimination with minor allele frequencies &gt; 5%. Pts were followed for progression-free (PFS) and overall survival (OS). Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes. Results: 60 pts with metastatic CRPC initiated on D enrolled. Demographics included: age (median) – 69 yrs, ECOG PS 0– 40%, prostate specific antigen (PSA) (median) – 129.9 ng/ml, PSA doubling time (median) – 1.8 months, visceral mets –25%. No clinical parameters were associated with PFS and OS. Significant SNP associations are summarized below. Conclusions: Differences in germ-line ABCG2, ABCB1, and TUBB4 SNPs may contribute to variation in clinical outcomes in CRPC pts treated with D. [Table: see text] [Table: see text]
Regular Article LYMPHOID NEOPLASIA Microenvironment-dependent proliferation and mitochondrial priming loss in mantle cell lymphoma is overcome by anti-CD20
Authors: David Chiron, Céline Bellanger, Antonin Papin, Benoit Tessoulin, Christelle Dousset, Sophie Maiga, Anne Moreau, Julie Esbelin, Valérie Trichet, Selina Chen-Kiang, Philippe Moreau, Cyrille Touzeau, Steven Le Gouill, Martine Amiot, Catherine Pellat-Deceunynck
Journal: Blood (2016)
Combination of antiangiogenic therapy using the mTOR inhibitor RAD001 (everolimus) and low-dose chemotherapy for locally advanced and/or metastatic pancreatic cancer: Dose-finding study.
Authors: Mareile Joka, Stefan Hubert Boeck, Christian Hosius, Laetitia Decroix, Christoph May, Barbara Alberter, Anette Pustowka, Volker Heinemann, Christiane Bruns
Journal: Journal of Clinical Oncology (2012)

360 Background: This was an open-label, multicenter two-arm combined phase I (dose finding, cohort 1-5)/II (dose expansion) study of continuous doses of RAD001 every 2 nd day or every day in combination with escalating low dose gemcitabine in patients (pts) with locally advanced and/or metastatic pancreatic cancer. The primary objective was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT). The secondary objectives were to characterize safety and tolerability and to evaluate preliminary efficacy (ORR). Methods: A total of 27 pts were enrolled in phase I. All of these were analyzed in the safety population and 23 pts in the MTD-determining population. In total, 21 pts completed the study. Results: The MTD was determined to be 500mg/m 2 /week gemcitabine and 5mg/d RAD001 (cohort 4, 7 pts treated). In total, 3 DLTs occured: hepatic toxicity and unknown DLT as worsed case assumption in cohort 5 and hepatic toxicity in cohort 4. Overall, 25 of 27 pts (92.59%) reported at least one AE. Thrombocytopenia was most frequent AE, followed by leukopenia and nausea. In the individual dose groups, thrombocytopenia was most common in cohorts 1, 2 and 5, leukopenia in cohort 3 and nausea in cohort 4. The majority of pts experienced AEs with suspected relation to study drug (81.48%), AEs leading to dose adjustments or temporary interruption (77.78%) or required concomitant medication (66.67%). A total of 11 pts (40.74%) experienced SAEs. Two pts died during the study (not related to study drug). 4 pts were dicontinued permanently due to 2 AEs and 2 SAEs. ORR was 13%. None of the pts reported complete response (CR), the progressive disease rate was 13%. The clinical benefit rate was 78.3%. Conclusions: The present study was prematurely terminated due to slow recruitment and the dose expansion phase (phase II) was not started. In phase I, the MTD was determined to be 500mg/m 2 /week Gemcitabine and 5mg/d RAD001. No new safety concerns were identified for combination of antiangiogenic therapy using the mTOR- inhibitor RAD001 (Everolimus) and low dose chemotherapy for locally advanced and/or metastatic pancreatic cancer.
Semi-Automatic Enrichment with High Resolution/Selected Reaction Monitoring (HR/SRM) Scan for the Detection of Urinary Hepcidin in Patients with Sickle Cell Disease
Authors: Xionghao Lin, Elena Afia Adjei, Namita Kumari, Sharmin Diaz, Marina Jerebtsova, Patricia A. Oneal, Sergei Nekhai
Journal: Blood (2015)
Use of sector analysis of I-125 permanent prostate brachytherapy to evaluate and compare pre- and postimplant dosimetry.
Authors: Ahamed Badusha Mohamed Yoosuf, Geraldine Workman, Monica M O'Toole, Margaret Straney, Rejina Verghis, Eoin Napier, Darren M. Mitchell
Journal: Journal of Clinical Oncology (2012)

242 Background: To evaluate 12 sector analysis in the assessment and comparison of pre- and post- implant dosimetric parameters during the development of an I-125 prostate brachytherapy (PPB) service. Methods: 50 consecutive men being treated with PPB had dose volume analysis in 12 sectors of their pre implant ultrasound (PI US ) and post implant CT (PI CT ) data using a Variseed 8.0 treatment planning system. PI US dosimetry was performed 2 weeks prior to implantation and PI CT dosimetry 4 weeks post implant. Individual sectors were created by dividing the cranio-caudal prostate length into 3 equal lengths creating prostate base (PB), midgland (PM) and apex (PA). Each of these volumes was then divided into four axial sectors (right and left anterior, right and left posterior). The planning target volume (PTV), dose to 90% of prostate (D 90 ), prostate volume enclosed by 100% (V 100 ), 150% (V 150 ) and 200% (V 200 ) dose were recorded in each sector on PI US and PI CT . Adjacent sectors on PI US were assessed for dose-volume homogeneity as were adjacent sectors on PI CT . Differences in individual sectors on PI US and PI CT were evaluated. Results: Adjacent sector analysis demonstrated dose homogeneity in all sectors of PI US and the majority of sectors on PI CT . Statistically significant differences between PI US and PI CT were noted in target volume, particularly in PB with PI CT &gt;PI US . When individual sectors on PI US and PI CT were compared, statistically significant differences were noted in the majority of dosimetric parameters. The anterior PB and PM were significantly lower on PI CT (p value &lt; 0.001) and significantly higher at the posterior PM and PA (p value &lt; 0.05). These changes were consistent across all analysed parameters. In particular, significant absolute differences in D90 in equivalent sectors on PI US and PI CT were seen. Conclusions: 12 sector analysis allows rapid assessment of PI US and PI CT dose and volume homogeneity. It offers a scientific method of identifying areas of relative over and under dosing on PI CT when compared with PI US providing both clinicians and physicists with a learning tool to refine dosimetric analysis and highlight sectors where implant quality could be improved.
Phase 2 Study of Allogeneic Stem Cell Transplantation (ASCT) From Matched Related Donor (MRD) In Patients Older Than 55 Years After Reduced Intensity Conditioning (RIC) Associating Fludarabine, Intravenous Busulfan and Rabbit Thymoglobulin
Authors: Didier Blaise, Mohamad Mohty, Jean Marie Boher, Noel Milpied, Nathalie Fegueux, Anne Sirvent, Sabine Furst, Mauricette Michallet, Jean El Cheikh, Luca Castagna, Patrice Chevallier, Jacques-Olivier Bay, Jean-Yves Cahn, Thierry Guillaume, Reda Bouabdallah, Norbert Vey, Reza Tabrizi, Christian Chabannon, Catherine Faucher
Journal: Blood (2010)
Targeting granulocyte‐macrophage colony‐stimulating factor in epithelial and vascular remodeling in experimental eosinophilic esophagitis
Authors: E. N. McNamee, K. A. Biette, J. Hammer, R. Harris, H. Miyazawa, J. J. Lee, G. T. Furuta, J. C. Masterson
Journal: Allergy (2016)

Eosinophilic esophagitis (EoE) is a chronic antigen-mediated clinicopathologic disease of the esophagus characterized by an eosinophil-predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis, and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting granulocyte-macrophage colony-stimulating factor (GM-CSF; an agonist cytokine linked with eosinophil survival and activation) would be protective in a preclinical model of EoE.Eosinophilic esophagitis-like esophageal inflammation was induced in the L2-IL5OXA EoE mouse model, and GM-CSF production was assessed by mRNA and protein analyses. Granulocyte-macrophage colony-stimulating factor-receptor-alpha expression patterns were examined by flow cytometric and immunofluorescence analysis. L2-IL5OXA EoE mice were treated with anti-GM-CSF neutralizing antibody or isotype control and assessed for histopathological indices of eosinophilia, epithelial hyperplasia, and angiogenesis by immunohistochemistry and RT-PCR.Significantly increased levels of esophageal GM-CSF expression was detected in the L2-IL5OXA mouse EoE model during active inflammation. Granulocyte-macrophage colony-stimulating factor-receptor-alpha was predominantly expressed on esophageal eosinophils during EoE, in addition to select cells within the lamina propria. Anti-GM-CSF neutralization in L2-IL5OXA EoE mice resulted in a significant diminution of epithelial eosinophilia in addition to basal cell hyperplasia and vascular remodeling. This treatment response was independent of effects on esophageal eosinophil maturation or activation.Granulocyte-macrophage colony-stimulating factor is a potential therapeutic target to reduce esophageal eosinophilia and remodeling.