tbuckley/cabot-search huggingface dataset:
Final results of a University of Chicago phase II consortium trial of sorafenib (SOR) in patients (pts) with imatinib (IM)- and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST).
Authors: N. P. Campbell, K. Wroblewski, R. G. Maki, D. R. D'Adamo, W. A. Chow, D. R. Gandara, C. Antonescu, W. M. Stadler, E. E. Vokes, H. L. Kindler
Journal: Journal of Clinical Oncology (2011)

4 Background: GIST pts who develop resistance to IM and SU have few therapeutic options. SOR inhibits KIT, VEGFR, PDGFR-β, and BRAF kinases. In preclinical models, SOR has activity against several IM-RES mutations that are resistant to SU (Heinrich. ASCO 2009). Methods: We performed a multi-center, phase II trial of SOR in unresectable, KIT-expressing GIST pts who had disease progression on IM by RECIST. After FDA approval of SU for IM-RES GIST, the study was amended in 2/07 to require progression after both IM and SU. Pts received SOR 400 mg orally twice daily. CT scans were obtained Q2 28-day cycles. The primary endpoint was objective response rate. A Simon minimax 2-stage design required 1 response in 18 pts to proceed to a second stage, and 4 responses in 32 IM/SU RES pts for further investigation. Results: 38 pts (6 IM-RES, 32 IM/SU-RES) enrolled 1/06-9/09 at 6 centers. Median follow-up for survivors: 31 months (mo). Pt characteristics: male 55%; median age 57 (range 42-85); PS 0/1/2: 47%/47%/6%. Median cycles: 4 (range 1-37). 63% pts had at least 1 dose reduction. Partial response (PR): 13% (1 IM-RES, 4 IM/SU-RES); stable disease (SD): 55% (3 IM-RES, 18 IM/SU-RES). Disease control rate (PR + SD): 68%. Median progression-free survival: 5.2 mo (95% CI: 3.4, 7.4). Median overall survival 11.6 mo (95% CI: 8.8, 18.0); 1-year survival 50%; 2-year survival 29%. Three pts remain on trial receiving study drug (1 PR at 34 mo; 2 SD at 18 and 37 mo). Grade 3/4 toxicities (% pts): hand-foot syndrome 45%, hypertension 21%, diarrhea 8%, hypophosphatemia 8%, GI bleed 5%, rash 5%, thrombosis 3%, GI perforation 3%, fatigue 3%, anemia 3%. Conclusions: SOR is active in IM-and SU-resistant GIST. Some pts treated with SOR experience prolonged disease control. SOR is well-tolerated in GIST pts, but dose reductions are often required. SOR warrants further investigation in GIST. Supported by NCI grant N01-CM-62201. [Table: see text]
Phase II , biomarker and genomic correlative study of GFL: Interferon gamma (IFN-γ), bolus/infusion 5-FU and leucovorin (LV) for metastatic colorectal cancer (mCRC)
Authors: Lee Schwartzberg, Janet Houghton, Darren Phillips, Clinton Stewart, Mihaela Onciu, James Geller, Mark Walker
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

4456 

Introduction: In vitro and in vivo xenograft studies demonstrate synergistic interaction between 5-FU and IFN-γ, dependent on upregulation of the Fas receptor and other IFN-γ regulated components of the extrinsic apoptosis pathway. IFN-γ has been combined safely with 5-FU/LV +/- bevacizumab in a Phase I trial and upregulates Fas expression in mCRC patients (Schwartzberg, ASCO GI 2006). We performed a phase II clinical trial with a molecular correlate companion study to assess markers of apoptosis, proliferation, and genomic expression of IFN-γ and 5-FU related genes in primary tumor, pre and post treatment biopsies. Methods: Chemotherapy naive (cohort 1) or prior chemotherapy resistant (cohort 2) mCRC patients were enrolled in a Phase II trial adding IFN-γ 150 mcg SQ immediately before and after a bolus/infusional 5-FU/LV regimen over 48 hr in a 14 day cycle. The primary endpoint was objective response by RECIST criteria assessed after 8 weeks. Patients in cohort 1 with stable disease at 8 weeks were eligible for the addition of bevacizumab to GFL. Blood samples for 5-FU and IFN-γ PK were obtained using a limited sampling model. Peripheral blood was obtained at 0, 6.5, 24, 48 and 96 hours to assess Fas expression in various cell compartments. Primary formalin fixed paraffin embedded tumor samples were available for most patients as were fresh frozen biopsies taken prior to initiation of GFL in 17 patients and immediately after cycle 1 in 15 patients. Results: Thirty six patients were enrolled, mean age 63.8 (range 42-89), 92% ECOG 0-1, 18 in cohort 1 and 18 in cohort 2. GFL was well tolerated with 17% experiencing highest grade adverse event (AE) grade 4, and 25% highest AE grade 3. Patient disposition as of 11/1/07 revealed 30 patients off study: 22 with disease progression, 4 investigator decision, 2 for adverse events, 2 withdrew consent; and 6 remaining on study. Intent to treat response analysis demonstrated 6/18 (33.3%) of cohort 1 had partial response (PR), 5 at week 8 and 1 after addition of bevacizumab. In cohort 2, 1/18 (5.6%) had PR and 10 had stable disease. Both cohorts met prespecified response boundaries to continue enrollment. Median time to progression in cohort 1 was 5.8 months and in cohort 2 was 4.1 months. Fas expression in neutrophils increased from mean (range) 1621 (12-4090) units at time zero to 2790 (772-5710) at 96 hours after IFN-γ, p<0.001. Conclusion: GFL is an active regimen in mCRC with response rates exceeding historical results with 5-FU/LV alone. DNA microarray analysis from primary tumor and biopsy samples are currently being analyzed and preliminary data will be compared to that obtained from xenograft models treated with the GFL combination. These results will be available at the time of the meeting.
A single-arm, open-label, phase 2 study of nab-paclitaxel and carboplatin chemotherapy plus necitumumab in the first-line treatment of patients with stage IV squamous non-small cell lung cancer (NSCLC)
Authors: M. Socinski, M. Gil, J. Shahidi, G.Y. Chao, L. Villaruz
Journal: Annals of Oncology (2016)
O-(2-18F-fluoroethyl)-L-tyrosine PET for evaluation of brain metastasis recurrence after radiotherapy: an effectiveness and cost-effectiveness analysis
Authors: Alexander Heinzel, Dirk Müller, Sareh Said Yekta-Michael, Garry Ceccon, Karl-Josef Langen, Felix M Mottaghy, Martin Wiesmann, Martin Kocher, Elke Hattingen, Norbert Galldiks
Journal: Neuro-Oncology (2017)

Conventional MRI is the standard method to diagnose recurrence of brain metastases after radiation. However, following radiation therapy, reactive transient blood-brain barrier alterations with consecutive contrast enhancement can mimic brain metastasis recurrence. Recent studies have suggested that O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET improves the correct differentiation of brain metastasis recurrence from radiation injury. Based on published evidence and clinical expert opinion, we analyzed effectiveness and cost-effectiveness of the use of FET PET in addition to MRI compared with MRI alone for the diagnosis of recurrent brain metastases.A decision-tree model was designed to compare the 2 diagnostic strategies from the perspective of the German Statutory Health Insurance (SHI) system. Effectiveness was defined as correct diagnosis of recurrent brain metastasis and was compared between FET PET with MRI and MRI alone. Costs were calculated for a baseline scenario and for a more expensive scenario. Robustness of the results was tested using sensitivity analyses.Compared with MRI alone, FET PET in combination with MRI increases the rate of correct diagnoses by 42% (number needed to diagnose of 3) with an incremental cost-effectiveness ratio of €2821 (baseline scenario) and €4014 (more expensive scenario) per correct diagnosis. The sensitivity analyses confirmed the robustness of the results.The model suggests that the additional use of FET PET with conventional MRI for the diagnosis of recurrent brain metastases may be cost-effective. Integration of FET PET has the potential to avoid overtreatment with corresponding costs as well as unnecessary side effects.
Alternative schedules of adjuvant temozolomide in glioblastoma multiforme: A 6-year experience
Authors: L. Buttolo, F. Giunta, V. D. Ferrari, S. Grisanti, G. Marini, P. Mortini
Journal: Journal of Clinical Oncology (2006)

1511 Background: Temozolomide (TMZ) is an oral alkylating agent with proven efficacy in the therapy of glioblastoma multiforme (GBM). The activity of TMZ is drug-exposure dependent, however dosages are primarily limited by myelotoxicity. In the attempt to increase survival while limiting toxicity, we treated GBM patients (pts) with one of 3 alternative adjuvant TMZ schedules, including a low-dose daily regimen. Methods: We assessedthe overall survival and the development of grade 3–4 myelotoxicity in pts with GBM who were treated in our centre (November 1998-October 2005), following surgery, with one of the following TMZ schedules: standard schedule (SS: 200–300 mg/m 2 × 5 days, every 28 days); extended schedule (ES: 150 mg/m 2 × 7 days every 15 days); daily schedule (DS: 75 mg/m 2 daily). Pts were treated until death or tumour progression. The analysis of survival was based on the Kaplan-Meier (KM) and the Cox models. Adverse events were graded according to NCICTC 3.0. Results: We evaluated 117 pts (73 m, 44 f, avg. age 57 yrs, 53% received radiotherapy, RT) with histologically diagnosed gliomas (GBM=92.3%) treated with TMZ SS (tot pts=48, RT pts=22, no. cycles: 1÷33, avg 6) or ES (tot pts=35; RT pts=19, no. cycles: 1÷43, avg 16) or DS (tot pts=34; RT pts=21, days of treatment: 25÷671, avg 212). The overall survival significantly differed among the 3 schedules (KM), with DS providing the best outcome (p=0.0357, log-rank). Median survival time was markedly increased in DS pts (DS=29.47 months; ES=15.73 months; SS=11.90 months) as well as the survival rate at 2 yrs after diagnosis (DS=51%; ES=30%; SS=21%). DS, but not ES, significantly reduced the mortality hazard ratio (HR) compared to SS (Cox: HR=0.494; IC95% 0.253–0.966, p=0.039). Grade 3–4 myelotoxicity (leukopenia, LP; neutropenia, NP; thrombocytopenia,TP) occurred less frequently with DS (NP=2.9%; TP=2.9%; any=5.9%) than with ES (LP=11.4%; NP=14.3%; TP=17.1%; any=28.6%) and SS (LP=14.6%; NP=8.3%; TP=20.8%; any=22.9%). Conclusions: In our experience with adjuvant TMZ in GBM, a continuous daily dose of 75 mg/m 2 was on the whole more advantageous than a standard monthly or a biweekly regimen, as it resulted in the highest overall survival with the lowest hematologic toxicity. No significant financial relationships to disclose.
Quantitative evaluation of HER2-mediated cellular uptake of the HER2-targeted antibody-liposomal doxorubicin conjugate MM-302 suggests potential for treating HER2-intermediate tumors
Authors: E. Geretti, C. Espelin, B. Adiwijaya, N. Dumont, S. Coma, Z. Koncki, G. Garcia, T. Bloom, V. Rimkunas, J. Reynolds, K. Campbell, V. Moyo, I. Molnar, P. Lorusso, K. Miller, C. Ma, I.E. Krop, P. Munster, T. Wickham
Journal: Annals of Oncology (2016)

MM-302 is a HER2-targeted antibody–liposomal doxorubicin conjugate designed to target doxorubicin to HER2-expressing tumor cells. MM-302 showed an acceptable safety profile and promising activity in a Phase I study in HER2-positive metastatic breast cancer (NCT01304797), and it is now being evaluated in a Phase II trial in the same setting (NCT02213744). The goal of this work is to determine the correlation between single-cell HER2 expression and liposome uptake on MM-302 patient biopsies as well as on preclinical tumor models. Frozen biopsies were collected 3 days post infusion of MM-302 (8-50 mg/m2; alone or in combination with trastuzumab, with or without cyclophosphamide), and stained for PEG (surrogate for MM-302), HER2 and cytokeratin, side-by-side with two cell standard arrays: A PEG array, obtained by cell incubation with increasing amounts of MM-302, and a HER2 array, containing a panel of cell lines at various HER2 levels. The HER2 expression and liposome uptake in individual tumor cells of the human samples was quantified based on the PEG and HER2 fluorescent intensities of the standards. MM-302 cellular delivery was investigated in vivo in IHC 0, 1 + , 2+ and 3+ tumor models. Uptake of MM-302 into HER2-expressing cells was detected in ∼80% of patient biopsies. Interestingly, HER2 expression within individual samples was found to be heterogeneous, ranging from ∼1 X 105 to over 1 X 106 HER2 receptors per cell. Evaluation of cellular HER2 expression and MM-302 uptake within the same sample revealed that the magnitude of MM-302 tumor cell uptake was comparable across the range of HER2 expression from ∼1 X 105 to over 1 X 106 HER2 receptors per cell. These findings were in line with preclinical in vivo studies showing HER2-mediated delivery of MM-302 to IHC 1 + , 2 + , and 3+ tumors but not to IHC 0 tumors. Our data suggest that MM-302 effectively targets tumor cells expressing various levels of HER2 in patients' tumors. Hence, in addition to treating HER2-positive patients, MM-302 may be a promising agent for treating patients with intermediate HER2 expression (HER2 IHC 1 + /2 + , FISH-negative).
Unusual Displacement of Urinary Bladder by a Dilated Rectosigmoid Colon on Bone Scintigraphy
Authors: Mehrosadat Alavi, Leila Kalhor, Tahereh Ghaedian
Journal: Clinical Nuclear Medicine (2017)

A 7-year-old boy with chief complaint of chronic pelvic pain was referred to our nuclear medicine department for bone scintigraphy. The images showed a focus of radiotracer activity in the right side of pelvic cavity, which is further confirmed as urinary bladder by single-photon emission computed tomography (SPECT) and delayed images. Because of high possibility of mass effect in pelvic cavity, pelvic magnetic resonance imaging (MRI) was performed, and it revealed an unusual dilatation of rectosigmoid colon with no evidence of pelvic mass.
The prognostic value of the cocaine and amphetamine-regulated transcript (CART) in breast cancer (BC).
Authors: D. P. O'Connor, D. J. Brennan, H. Laursen, S. F. McGee, S. McCarthy, R. Zagozdzon, E. Rexhepaj, A. Culhane, F. M. Martin, M. J. Duffy, G. Landberg, L. Ryden, S. M. Hewitt, M. J. Kuhar, R. Bernards, R. C. Millikan, J. Crown, K. Jirstrom, W. M. Gallagher
Journal: Journal of Clinical Oncology (2011)

601 Background: Previously, we reported a bioinformatic re-analysis of the Van’t Veer et al. BC dataset that identified CART as a putative indicator of poor prognosis. CART is a neuropeptide hormone implicated in multiple patho-physiological processes. Here, we examine the prognostic value of CART in BC and its molecular mechanism of action in vitro. Methods: CART protein expression was assessed by immunohistochemistry and automated image analysis on tissue microarrays from two independent BC cohorts (n = 690). CART mRNA expression was assessed in a third cohort (n = 155). Kaplan-Meier analysis and the log rank test were used to illustrate differences between overall survival (OS) and recurrence free survival (RFS) according to CART protein and mRNA expression. Cox regression proportional hazards models were used to estimate the relationship between outcome and CART expression, grade, age, nodal status, ER status, PR status, Her2, Ki-67 and tumor size. Amplification of the CART signal and CART-mediated transcriptional activation of ERa were examined by Western blotting and luciferase reporter assay, while flow cytometry was used to examine the effect of CART expression on the response of BC cells to tamoxifen (TAM). Results: We show that CART is expressed in primary and metastatic BC and, using a consistently applied threshold for definition of CART levels in two separate cohorts (median intensity +/− 1 standard deviation), that high CART expression is an independent poor prognostic marker in lymph node− negative (LN−) (p=0.0025) and ER+ (p=0.0003) BC. We also show that CART mediates an autocrine/paracrine effect leading to amplification of the CART signal in BC cells. Furthermore, CART increases transcriptional activity of ERa in a ligand-independent manner via the mitogen-activated protein kinase (MAPK) pathway. Finally, we show that ectopic expression of CART in two independent ER+ BC cell lines protects against TAM-mediated cell death and that high CART expression predicts outcome in 3 independent TAM-treated BC cohorts. Conclusions: CART is an independent prognostic factor in LN− BC and predicts outcome of patients treated with TAM, which we believe occurs through the ligand-independent activation of ERa.
Hyperplasia of the Prostate: Reply
Authors: Peter Greenwald
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Hyperplasia of the Prostate: Reply Get access Peter Greenwald, M.D. Peter Greenwald, M.D. State of New York Department of HealthAlbany, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 2, February 1975, Page 524, https://doi.org/10.1093/jnci/54.2.524-a Published: 01 February 1975
Customer Satisfaction of CAS (Centro Accoglienza e Servizi) Dr. ssa Roberta Fornara2, Dr. Elena Castiglioni1, Dr. Alice Gatti1, CPSI Monica Bacchetta1, Dr. Incoronata Romaniello1 1 SSVD di Oncologia -Ospedale SS Trinità di Borgomanero- ASL NO 2 Servizio di Psicologia ASL NO
Authors: R. Fornara, I. Romaniello, M. Bacchetta, E. Castiglioni, A. Gatti
Journal: Annals of Oncology (2016)
Quality of resection and outcome in stage III thymic epithelial tumors (TET): A retrospective analysis of 150 cases from the national network RYTHMIC experience
Authors: M.V. Bluthgen, E. Dansin, D. Ou, H. Lena, J. Mazieres, E. Pichon, F. Thillays, G. Massard, X. Quantin, Y. Oulkhouir, T. Nguyen Tan Hon, L. Thiberville, C. Clement-Duchene, C. Lindsay, P. Missy, T. Molina, N. Girard, B. Besse, P. Thomas
Journal: Annals of Oncology (2016)
EXTH-12. β-ELEMENE SELECTIVELY INHIBITS THE PROLIFERATION OF GLIOMA STEM-LIKE CELLS THROUGH NOTCH1 DOWNREGULATION
Authors: Zhong-ping Chen, Hai-bing Feng, Jian Wang
Journal: Neuro-Oncology (2016)

Beta-elemene (β-ELE) is a compound from a Chinese herb whose anti-cancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem-like cells (GSLCs) has not yet been reported. The inhibitory effect of β-ELE (with or without temozolomide) to GSLCs and parental cells were checked in vitro and in vivo. The molecular mechanisms were also investigated. We have found that β-ELE selectively inhibited the proliferation and sphere formation of GSLCs other than parental glioma cells, while TMZ exerted its effects on parental cells instead of GSLCs. The in vivo data confirmed that the combination of β-ELE and TMZ worked better in the xenografts of GSLCs. Notch1 was downregulated upon β-ELE treatment. Our data also demonstrated that the continuous administration of β-ELE produces an ideal effect to control tumor progression in vivo. Our finding demonstrated that β-ELE could compensate for TMZ to kill both GSLCs and non-stem like cancer cells. Notch1 might be a downstream target of β-ELE. Therefore, our data shed light on improving the outcome of glioma patients by combining β-ELE and TMZ.
The patients' understanding of clinical research
Authors: B. Rudnas, E. Montanari, M. Dall'Agata, E. Petracci, P. Serra, A. Piancastelli, B. Vertogen, F. Zumaglini, B. Venturini, S. Testoni, V. Gallà, M. Monti, D. Andreis, F. Pagan, A. Ragazzini, F. Fabbri, G. Gentili, A. Affatato, O. Nanni
Journal: Annals of Oncology (2016)
Mutations in Histone Modulators and HOXA5 Methylation Levels Affects Survival in Azacitidine Treated MDS Patients
Authors: Magnus Tobiasson, Mohsen Karimi, Marios Dimitriou, Ying Qu, Andreas Lennartsson, Hani Abdulkadir Ali, Ashwin Unnikrishnan, Martin Jadersten, Monika Jansson, Asmaa Ben Azenkoud, John E Pimanda, Karl Ekwall, Johanna Ungerstedt, Soren Lehmann, Eva Hellstrom-Lindberg
Journal: Blood (2014)
CBIO-04. EXOSOMES FROM CELLS HARBORING PTPRZ1-MET FUSION CONTRIBUTE TO A MALIGNANT PHENOTYPE AND TEMOZOLOMIDE CHEMORESISTANCE IN GLIOBLASTOMA
Authors: Ailiang Zeng, Chunsheng Kang, Yongping You
Journal: Neuro-Oncology (2016)

It is validated that exosomes are carriers of pro-tumorigenic factors that participate in glioblastoma progression. Many gene fusions are strong driver mutations in neoplasia and are involved in tumorigenesis. However, whether gene fusions are transduced by exosomes is unknown. We characterized exosomes from the medium of glioblastoma cells harboring and not harboring PTPRZ1-MET fusion (ZM fusion). We also determined the effect of the ZM exosomes on pro-oncogenic secretions from the cells with ZM fusion and showed how exosomes are internalized into the recipient cells, and studied the effect of exosome-mediated intercellular communication in the glioblastoma microenvironment. MET proto-oncogene expression was higher in exosomes from the cells with ZM fusion (ZM exosomes). Phosphorylated MET (p-MET) was detected only in ZM exosomes, and not in non- ZM exosomes. ZM exosomes transferred to non–ZM fusion glioblastoma cells and normal human astrocytes altered gene expression and induced mesenchymal–epithelial transition.The uptake of ZM exosomes induced an exosome-dependent phenotype defined by glioblastoma cell migration and invasion, neurosphere growth and angiogenesis. Additionally, ZM exosomes conferred temozolomide resistance to the glioblastoma cells. Exosomes-derived ZM fusion network proteins targeted multiple pro-oncogenic effectors in recipient cells within the glioblastoma microenvironment. Our findings show how exosomes mediate the aggressive character of glioblastoma and how ZM fusion can aggravate it, with possible implications for the foundation of gene fusion–based therapy for managing glioblastoma.
Stoicism and its relation with clincal-pathological variables in patients with resected cancer undergoing adjuvant chemotherapy treatment
Authors: A. Ramchandani Vaswani, C. Calderon Garrido, P. Jimenez Fonseca, A. Carmona-Bayonas, E. Llabrés Valentí, C. Beato Zambrano, T. García, M.D.M. Muñoz, B. Castelo, E. Martinez de Castro, J. Rogado Revuelta, M.D. Fenor, M. Mangas Izquierdo, M.Á Vicente, O. Higuera, P.L.a. De Morena, M.D.L.N. Gomez Camacho, S. Fernández Arrojo, M.D.M. Soriano, C. Jara
Journal: Annals of Oncology (2016)
A Bayesian Observer Model of Drug Craving
Authors: Xiaosi Gu, Francesca Filbey
Journal: JAMA Psychiatry (2017)

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