tbuckley/cabot-search huggingface dataset:
Depletion of γ-catenin by Histone Deacetylase Inhibition Confers Elimination of CML Stem Cells in Combination with Imatinib
Authors: Yanli Jin, Yiwu Yao, Li Chen, Xiaohui Zhu, Bei Jin, Yingying Shen, Juan Li, Xin Du, Yuhong Lu, Sheng Jiang, Jingxuan Pan
Journal: Theranostics (2016)

Quiescent leukemia stem cells (LSCs) that are insensitive to BCR-ABL tyrosine kinase inhibitors confer resistance to imatinib in chronic myelogenous leukemia (CML).Identifying proteins to regulate survival and stemness of LSCs is urgently needed.Although histone deacetylase inhibitors (HDACis) can eliminate quiescent LSCs in CML, little is known about the underlying mechanism that HDACis kill LSCs.By fishing with a biotin-labeled probe, we identified that HDACi JSL-1 bound to the protein γ-catenin.γ-Catenin expression was higher in LSCs from CML patients than normal hematopoietic stem cells.Silencing γ-catenin in human CML CD34 + bone-marrow (BM) cells sufficiently eliminated LSCs, which suggests that γ-catenin is required for survival of CML LSCs.Pharmacological inhibition of γ-catenin thwarted survival and self-renewal of human CML CD34 + cells in vitro, and of murine LSCs in BCR-ABL-driven CML mice.γ-Catenin inhibition reduced long-term engraftment of human CML CD34 + cells in NOD.Cg-Prkdc scid II2rg tm1Sug /JicCrl (NOG) mice.Silencing γ-catenin by shRNA in human primary CD34 + cells did not alter β-catenin, implying a β-catenin-independent role of γ-catenin in survival and self-renewal of CML LSCs.Taken together, our findings validate that γ-catenin may be a novel therapeutic target of LSCs, and suppression of γ-catenin by HDACi may explain elimination of CML LSCs.
Metabolic Dysfunction, Obesity, and Survival Among Patients With Early-Stage Colorectal Cancer
Authors: Elizabeth M. Cespedes Feliciano, Candyce H. Kroenke, Jeffrey A. Meyerhardt, Carla M. Prado, Patrick T. Bradshaw, Andrew J. Dannenberg, Marilyn L. Kwan, Jingjie Xiao, Charles Quesenberry, Erin K. Weltzien, Adrienne L. Castillo, Bette J. Caan
Journal: Journal of Clinical Oncology (2016)

Purpose The effects of obesity and metabolic dysregulation on cancer survival are inconsistent. To identify high-risk subgroups of obese patients and to examine the joint association of metabolic syndrome (MetSyn) in combination with obesity, we categorized patients with early-stage (I to III) colorectal cancer (CRC) into four metabolic categories defined by the presence of MetSyn and/or obesity and examined associations with survival. Methods We studied 2,446 patients diagnosed from 2006 to 2011 at Kaiser Permanente. We assumed MetSyn if patients had three or more of five components present at diagnosis: fasting glucose &gt; 100 mg/dL or diabetes; elevated blood pressure (systolic ≥ 130 mm Hg, diastolic ≥ 85 mm Hg, or antihypertensives); HDL cholesterol &lt; 40 mg/dL (men) or &lt; 50 mg/dL (women); triglycerides ≥ 150 mg/dL or antilipids; and/or highest sex-specific quartile of visceral fat by computed tomography scan (in lieu of waist circumference). We then classified participants according to the presence (or absence) of MetSyn and obesity (BMI &lt; 30 or ≥ 30 kg/m 2 ) and assessed associations with overall and CRC-related survival using Cox proportional hazards models adjusted for demographic, tumor, and treatment factors and muscle mass at diagnosis. Results Over a median follow-up of 6 years, 601 patients died, 325 as a result of CRC. Mean (SD) age was 64 (11) years. Compared with the reference of nonobese patients without MetSyn (n = 1,225), for overall survival the hazard ratios (HR) and 95% CIs were 1.45 (1.12 to 1.82) for obese patients with MetSyn (n = 480); 1.09 (0.83 to 1.44) for the nonobese with MetSyn (n = 417), and 1.00 (0.80 to 1.26) for obese patients without MetSyn (n = 324). Obesity with MetSyn also predicted CRC-related survival: 1.49 (1.09 to 2.02). The hazard of death increased with the number of MetSyn components present, independent of obesity. Conclusion Patients with early-stage CRC with obesity and MetSyn have worse survival, overall and CRC related.
Phase I study of PM00104 in combination with carboplatin (C) in patients (pts) with advanced solid tumors.
Authors: E. Calvo, M. Gil, C. Coronado, A. Valer, I. Duran, M. Hidalgo, B. Pardo, A. Calles, M. García, P. Morelli, C. M. Kahatt, R. Prados, C. Fernandez, R. Salazar
Journal: Journal of Clinical Oncology (2011)

e13085 Background: PM00104 (Zalypsis, Z) is a synthetic alkaloid related to Jorumycin with a strong antitumor activity against a wide variety of tumor lines. In vivo data of synergism between Z and a platinum compound against human gastric and bladder xenografts prompted this study. The objetive is to identify the maximum tolerated dose (MTD) and the recommended dose (RD) of C given on day (d) 1 followed by Z as a 1-hour i.v. infusion on d1, every three weeks, as well as safety and feasibility, pharmacokinetic (PK) analysis and antitumor activity Methods: 19 pts with metastatic or advanced solid tumors were enrolled and a 3+3 dose escalation design was followed. If a dose-limiting toxicity (DLT) was deemed associated with prior treatment, separate cohort expansion into heavily or mildly pretreated (HP or MP) groups were to be conducted at each dose level (DL) Results: Median age was 60 (34-73) years; male/female, 10:9; ECOG 0/1, 9:10. Most frequent cancers were colon (n=4) and breast (n=3). After recruitment of 3 evaluable pts at DL1 (3 AUC C and 2 mg/m2 Z), 1 DLT was found in 1 HP pt, leading to cohort stratification. Three MP pts were included and 1 DLT was also seen. Hence, both cohorts had to be expanded to include 6 pt in each group. As no more DLTs arose, a new cohort of MP pts was treated at DL2 (4 AUC C and 2 mg/m2 Z), while recruitment of HP pts was put on hold. Because 2/6 MP pts had DLTs, DL2 was declared the MTD. DL1 was considered the RD. All 4 DLTs (HP, 1; MP, 3) were grade (G) 4 thrombocytopenia regardless of the group. G 3-4 toxicities including DLTs were neutropenia, thrombocytopenia, nausea, vomiting, and diarrhea. Preliminary PK parameters showed similar characteristics to single-agent Z: mean AUC, 81.55 h·ng/ml; Cmax, 29.53 ng/ml; CL, 48.59 L/h. Target AUC 3 and 4 for C were 2.6 and 3.9 mg/ml·min, respectively. No PK interactions were detected for Z or for C. Three pts had disease stabilizations > 3 months, of whom 1 pt had tumor shrinkage of 28 % (breast cancer) Conclusions: In this study heavy or mild pretreatment did not have a major impact in drug escalation. RD for this schedule was 3 AUC C and 2 mg/m2 Z, however the combination suggests an overlapping toxicity that hampers dose escalation of either of the compounds. Updated results will be presented.
Validating RNAseq-signatures of vorinostat (VOR) sensitivity and resistance in patients with newly diagnosed glioblastoma (GBM) treated with VOR, temozolomide and radiation therapy in Alliance N0874/ABTC-0902.
Authors: S. Keith Anderson, C. Ryan Miller, Jann Nagina Sarkaria, Kurt A. Jaeckle, Jan C. Buckner, Keith L. Ligon, Karla V. Ballman, Dennis Frederic Moore, David Schiff, Manmeet Singh Ahluwalia, Eudocia Quant Lee, Laura E. Horvath, Elizabeth Robins Gerstner, Glenn Jay Lesser, Michael Prados, Stuart A. Grossman, Caterina Giannini, Patrick Y. Wen, Evanthia Galanis
Journal: Journal of Clinical Oncology (2016)

2029 Background: Five RNAseq-based gene set enrichment analysis (GSEA) signatures (sig) were previously developed in pre-clinical models to predict sensitivity or resistance to treatment with the HDAC inhibitor VOR. This study investigates if these signatures can identify groups of newly diagnosed GBM patients (pts) deriving benefit from being treated with VOR in addition to standard chemoradiation. Methods: Baseline tumor samples were obtained from 76 pts enrolled on the Phase II single arm trial N0874 (Galanis, et al., ASCO 2014). RNAseq-based GSEA sig scores were calculated for four VOR-sensitivity sig (9, 77, 80, and 139) and one VOR-resistance sig (79). Overall survival (OS) and progression free survival (PFS) were used to evaluate univariate cut-points for each signature. Recursive partitioning (rpart) was used to simultaneously evaluate age, MGMT status, and the five sig scores to identify patient groups with differences in OS and PFS. Kaplan-Meier analysis was used to evaluate OS and PFS using the best cut-points and partitions. Results: Higher scores for sig 77, 80, and 139 all had at least one univariate cut-point associated with a statistically significant improvement for PFS (HR 0.55, 0.54, and 0.5 respectively, all p < 0.05). Higher scores for sig 79 had a univariate cut-point related to lower PFS (HR = 1.7, p = 0.028). Only sig 139 had a univariate cut-point related to OS (HR = 0.45, p = 0.039). Rpart for OS and PFS resulted in 5 groups of pts for each. Pts with high 79-scores had shorter OS and PFS. Pts with low 139-scores had shorter PFS, even if sig79 scores were low. MGMT methylation status did not affect the negative association of sig79 with PFS and OS and positive association of sig139 with PFS. Conclusions: Pts with high scores for the VOR-resistant signature 79 have shorter PFS and OS and patients with high scores on the VOR-sensitive signature 139 have a longer PFS and OS. These results suggest that these signatures could be useful in identifying subgroups of GBM patients that might derive benefit from VOR treatment. Clinical trial information: NCT00731731.
Sepsis in Patients with Febrile Neutropenia: A Clinical and Autopsy-Based Study
Authors: Thamires Branco Da Silva, Guilherme Rossi Assis de Mendonça, Maiara Marx Luz Fiusa, Brunna Eulalio Alves, Rodolfo Monteiro Enz Hubert, Melina Veiga Rodrigues, Vanessa Miho Tani, Jose Vassallo, Fabio Rogério, Erich Vinicius De Paula
Journal: Blood (2015)
Predictive value of circulating tumor cells for response to therapy in women with recurrent epithelial ovarian cancer.
Authors: D. Kindelberger, K. Daniels, E. Kantoff, T. Atkinson, J. Liu, S. M. Campos, S. T. Berlin, E. Cibas, U. Matulonis
Journal: Journal of Clinical Oncology (2010)

5111 Background: Circulating tumor cells (CTC's) can be used for detection of cancer recurrence and response to therapy. Epithelial ovarian cancer is diagnosed in an advanced stage in > 75% of patients, and despite high RR's of platinum- and taxane- based chemotherapy following diagnosis, most women will recur. The purpose of this study was to examine the utility of immunomagnetically-isolated CTC's, captured using the CellSearch System (Veridex) in predicting response to therapy in patients with known recurrent ovarian cancer. Methods: 50 consecutive patients with recurrent ovarian cancer (both platinum resistant and plat sensitive) were selected as part of an IRB-approved study at the Dana-Farber Cancer Institute. CTC's were isolated according to standard protocols for the Veridex CellSearch System. 7.5 mL of blood was collected in Cell Save Vacutainer tubes, samples were processed within 36 hrs of collection, and samples were immediately processed with the CellTracks Autoprep instrument using the Epithelial Cell Kit. Following processing, tumor cells were enumerated using the CellTracks Analyzer. Results: The mean age of the 50 patients was 56 years (range 37-81 yrs). CTC counts ranged from 0 to 8, with an average value of 7. No consistent trend was noted, as some patients' CTC counts increased through the study as others decreased, and these trends did not correlate with CA-125 levels or clinical/radiographic evidence of disease status. 24 pts patients underwent single agent chemotherapy (i.e., doxil, carboplatin, and topotecan), while 20 were placed on multiagent chemotherapy regimens; the remainder received biologic therapies. There was no correlation between CTC levels and the type of therapy, either single agent versus platinum doublet. Conclusions: The numbers of CTC's enumerated were quite low in all patients and failed to correlate with type or duration of chemotherapy. Additionally, the numbers of CTC's did not appear to correlate with CA-125 levels or with other modalities to measure treatment response in this patient population. Additional studies are needed to optimize the role for the enumeration of CTC's in monitoring patents with recurrent ovarian cancer. No significant financial relationships to disclose.
Pre-treatment circulating tumor DNA as a biomarker for disease burden in diffuse large B cell lymphoma (DLBCL).
Authors: Florian Scherer, David Matthew Kurtz, Michael Richard Green, Aaron M. Newman, Daniel M. Klass, Li Zhou, Rashi Krishnan, Chih Long Liu, Cynthia Glover, Robert S. Ohgami, Rodney J Hicks, Colm Keane, Katherine A Kong, Malek Faham, Mark S. Hertzberg, Maher K Gandhi, Ranjana H. Advani, Ronald Levy, Maximilian Diehn, Ash A. Alizadeh
Journal: Journal of Clinical Oncology (2015)

8539 Background: Patients with DLBCL reveal striking heterogeneity in clinical outcomes. Plasma cell-free DNA (cfDNA) levels have been shown to be adversely prognostic. Both circulating tumor DNA (ctDNA) as a minor fraction of cfDNA and circulating tumor cells (CTCs) can be used for DLBCL monitoring with ctDNA reported to be superior (Kurtz et al 2014 ASCO). However, the relationship between ctDNA and CTC levels with DLBCL clinical indices remains poorly defined. Methods: We profiled 43 DLBCL patients treated with R-CHOP based therapy and quantified their pre-treatment cfDNA, ctDNA and CTC levels. Pre-treatment ctDNA levels were determined by high-throughput sequencing of tumor specific immunoglobulin genes (Ig-HTS) of plasma cfDNA, and CTCs were enumerated by Ig-HTS of blood leukocytes. Metabolic tumor volume (MTV) was measured from pre-treatment 18FDG PET/CT scans using MetaVol. Parametric vs. non-parametric tests supported identical conclusions. Results: Blood cfDNA levels varied widely (2.8-1,713.5 ng/mL, median: 12.6), as did ctDNA levels (0-129,928 molecules/mL, median 87.5) and CTCs (0-454,400 CTCs/million cells, median 6.6). Total cfDNA levels and the amount of ctDNA were strongly associated (r = 0.73, P < 0.0001). Both cfDNA and ctDNA levels were significantly correlated with LDH (r = 0.79 and 0.74, P < 0.0001) and MTV (r = 0.62 and 0.53, P < 0.0001 and P = 0.002). CtDNA was detectable in 14 of 19 patients (74%) with normal LDH levels. Higher cfDNA and ctDNA levels were associated with adverse prognostic parameters including advanced stage (P < 0.0001 and P = 0.04), IPI 3-5 (P < 0.0001 and P = 0.04), marrow involvement (P = 0.04 and P = 0.009) and presence of B-symptoms (P = 0.0003 and P = 0.0001). CTCs levels were not associated with any of these prognostic parameters, despite showing a correlation with LDH (r = 0.43, P = 0.02). Conclusions: Our study demonstrates that, in contrast to CTCs, ctDNA levels better capture disease burden in DLBCL, including tumor volume and metabolic properties. The prognostic value of cfDNA levels appears directly related to ctDNA levels, and not to CTCs. Therefore, ctDNA is a specific biomarker of tumor burden in DLBCL and, compared to cfDNA, less prone to physiological perturbations.
Mutation Profiling of Therapy-Related Myeloid Neoplasms Using Next-Generation Sequencing Demonstrates Distinct Profiles from De Novo Disease
Authors: Alan H. Shih, Franck Rapaport, Stephen S. Chung, Emily K Dolezal, Sean Hobson, Mary K Amato, Christopher Y. Park, Mikkael A. Sekeres, Marcel R.M. van den Brink, Stephen Nimer, Ross L. Levine, Jaroslaw P. Maciejewski, Virginia M. Klimek
Journal: Blood (2014)
Surveillance for Recurrence of Colorectal Cancer
Authors: Marsela Sinjari, Giada Zoccoli, Giovanni Codacci-Pisanelli
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Self-Study Program IV: Nuclear Medicine: Oncology: Topics 5 and 6, Bone Cancer Therapy and Radioimmunotherapy
Authors: Andrew M. Keenan
Journal: Clinical Nuclear Medicine (2001)

Prince George\'s Hospital Center Cheverly, Maryland CLINICAL NUCLEAR MEDICINE publishes in each issue a section of references to articles of interest to its readers taken from the world medical literature. Articles below were selected from listings received through February 1, 2001. Slavic and Oriental language articles have English summaries unless marked with an asterisk after language abbreviation.
The windmills of your mind
Authors: Jeffrey C McIlwain
Journal: BMJ (2008)

The notion that healthcare professionals do not care about quality is risible. Ham’s illustration of the illusion of finance, finance, finance as the modus operandi of health care shows how badly the politicians who run and manage the NHS appreciate the issues.1 Successive “solutions” have been dominated by political meddling—for example, the National Patient Safety Agency. The educational role …
“It’s just a bit of colic,” they said
Authors: Salma Patel
Journal: BMJ (2016)

It's just a bit of colic," they saidSalma Patel shares the feeling of trying to be heard rather than reassured when accessing care for her child Salma PatelThe first four months of our daughter's life were very difficult.She cried constantly during the day, napped for only five to 10 minute durations, breastfed for two to five minutes at a time, hiccupped at least 50 times in one go three to four times a day, and made strange grunting noises in her sleep.When I sought help from healthcare professionals, they always began by asking if I was a first time mother.I was.They would then sigh and tell me that my baby's behaviour was completely normal: "It's just a bit of colic, it'll pass."I began to feel as if they'd labelled me as a hypochondriac because my daughter was my first child.I wanted them to investigate, to ask for details about when she cried, how much she cried, whether there was anything else we were worried about; we wanted them to explain colic.On the suggestion of other mothers, we got our daughter's posterior tongue tie and lip tie lasered, and took her for cranial osteopathy, but they didn't help.
Impact of early detection strategies on cancer mortality in germline<i>TP53</i> mutation carriers in Li-Fraumeni syndrome.
Authors: A. Villani, U. Tabori, J. D. Schiffman, A. Shlien, H. Druker, A. Novokmet, J. L. Finlay, D. Malkin
Journal: Journal of Clinical Oncology (2010)

1509 Background: Li-Fraumeni syndrome (LFS) carries a staggering lifetime risk of developing cancer. However, to date, routine biochemical and radiographic surveillance has been discouraged due to the lack of evidence supporting its effectiveness. Methods: A clinical surveillance protocol for LFS has been implemented at The Hospital for Sick Children in Toronto and has been adopted by several institutions in the United States. TP53 mutation analysis and complete family histories, including site and age at diagnosis of neoplasms, were prospectively collected for 8 LFS families who have members participating in this protocol. Results: Among the eight families, 49 TP53 mutation carriers were identified. The surveillance protocol detected 9 tumors in 6 of 16 TP53 mutation carriers who were screened. All 16 are alive after a mean follow-up time of 38 months compared with 11/33 (33.3%) TP53 mutation carriers who did not undergo surveillance (p = 5.29 × 10-6). All 6 TP53 mutation carriers (100%) who developed cancers identified by the surveillance protocol are alive with no evidence of disease, compared with only 5/27 (18.5%) TP53 mutation carriers who developed cancers and who did not undergo surveillance (p = 4.17 × 10-4). Conclusions: We demonstrate that a clinical surveillance protocol can detect asymptomatic neoplasms in carriers of a germline TP53 mutation, and can significantly reduce cancer mortality among these patients. This report therefore lends support for genetic screening and surveillance of patients suspected of having LFS. No significant financial relationships to disclose.
Results from a pilot study of nimotuzumab with concurrent chemoradiation in patients with locally advanced squamous cell carcinoma of head and neck.
Authors: M. Gupta, V. Madholia, N. Gupta, K. T. Bhowmik
Journal: Journal of Clinical Oncology (2010)

5565 Background: We sought to improve outcomes for patients with locally advanced carcinoma of head and neck (SCCHN) by testing the efficacy and safety of nimotuzumab with concurrent chemoradiotherapy. Methods: Eligible patients had stage III to IVa SCCHN. Treatment included cisplatin in dose of (40 mg/m2) once weekly for six weeks; radiotherapy up to a total dose of 66 Gy in 33 fractions/2Gy per fraction over 6.5 weeks with reduced field planning at 44 Gy/22 fractions and nimotuzumab 200 mg intravenous infusion for 60 minutes, once in a week for 6 weeks. The primary end points were response rate and safety. Results: Seventeen patients were enrolled from October 2007 to September 2009- 12 male and 5 female, (mean age, 54 years; range, 30 to 70 years; median Karnofsky status 80%; range 70% to 90%; oropharynx - 7, hypopharynx - 5, larynx - 5; stage IV disease - 41%). All patients completed 6 cycles of treatment with nimotuzumab. Patients were evaluated for primary end point at 24 weeks post treatment. The objective response rate was -76% with 10 patients in CR, 3 patients in PR and 2 patients were in stable disease while 2 patients showed progressive disease during 5th and 6th month. There was no grade III or IV adverse event. Overall nimotuzumab with concurrent chemoradiotherapy was safe and well tolerated. Conclusions: This study demonstrates the safety and efficacy of treatment of locally advanced SCCHN with nimotuzumab plus concurrent chemoradiation. This regimen has led to improved outcomes in terms of locoregional response and warrants for a large study to establish the clinical and survival benefits. No significant financial relationships to disclose.