tbuckley/cabot-search huggingface dataset:
Role of CXCL12-Expressing Mesenchymal Stromal Cell Niches in Maintaining Treatment-Resistant Leukemia Stem Cells
Authors: Puneet Agarwal, Stephan Isringhausen, Hui Li, Andrew J Paterson, Jianbo He, Takashi Nagasawa, Cesar Nombela-Arrieta, Puneet Agarwal
Journal: Blood (2018)
Inappropriate Celebration in the Presence of Patients With Poor Prognosis—The Cancer Center Victory Bell
Authors: Kevin J. Gale
Journal: JAMA Oncology (2018)

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Effect of Bibb-515 on resistance to chlorambucil and lomustine in dog lymphoma (OSW) cells.
Authors: Monika Arya, Ravi Kiran Bobba, Indira Benakanakere, Tyler Johnson, Carl Freter
Journal: Journal of Clinical Oncology (2014)

e19522 Background: BIBB-515 is a cholesterol synthesis inhibitor that has shown promise in increasing sensitivity to and reducing dose requirement of chemotherapeutic agents in Lymphoma cells in laboratory setting. Methods: To explore if this approach could be used in a canine clinical trial we used BIBB-515 in combination with Chlorambucil and Lomustine in a dog Lymphoma model using OSW cells. OSW represents one of the few reported canine Lymphoma cell lines and is the most thoroughly characterized. Results: PBMCs (peripheral blood mononuclear cells) isolated from patient’s whole blood and treated with cholesterol synthesis inhibitors in combination with Rituximab in laboratory setting showed reduced cell viability from 92% to 79% (P<.001). The combination of cholesterol inhibitors and Rituximab and Fludarabine was able to reduce cell viability from 67% in Fludarabine alone arm to 55% with combination treatment (P<.001). Similarly, in canine OSW cells, BIBB-515, used in combination with Chlorambucil (as low as 100nM), was able to reduce the cell proliferation from 100% in control and 98% in Chlorambucil alone to 49% in BIBB-515 and Chlorambucil (P<.001). BIBB-515 was also able to reduce cell proliferation in the Lomustine group from 100% in control and 103% in Lomustine alone to 43% in BIBB-515 and Lomustine group (P<0.001). The results were highly significant statistically in the study of both drugs. Conclusions: BIBB-515 is a promising new agent that increases sensitivity of Lymphoma cells to conventional chemotherapeutic agents, thereby reducing tumor cell proliferation. Clinically, this could translate into BIBB-515 having potential to allow reduction in therapeutic dose of chemotherapeutic agents, in effect decreasing chemotherapeutic drug resistance.
Dynamic analysis of CA-125 decline during neoadjuvant chemotherapy in patients with epithelial ovarian cancer as a predictor for sensitivity to platinum.
Authors: Roman Rouzier, Aurelie Pelissier, Claire Bonneau, Elisabeth Chereau, Virginie Fourchotte, Emile Darai, Thibault De La Motte Rouge
Journal: Journal of Clinical Oncology (2014)

e16536 Background: Platinum-based chemotherapy agents are major drugs in ovarian cancer. The platinum-sensitivity of disease is defined by treatment-free interval (recurrence-free interval>12 months). Our objective was to evaluate the pharmacokinetic parameters of serum CA 125 during neoadjuvant platinum-based chemotherapy (NAC), in patients with epithelial ovarian cancer, to identify a surrogate marker of sensitivity to platinum. Methods: Patients were selected from a population of epithelial ovarian cancer diagnosed between 2002 and 2009. Patients treated with NAC and interval debulking surgery were included. Demographic data, CA 125 concentrations, radiographic, surgical and pathologic data were obtained. Univariate and multivariate analyses were conducted to test the association between CA 125 kinetics and the platinum-sensitivity. ROC analysis was used to determine the optimal threshold of CA 125 for prediction of platinum-sensitivity. Results: One hundred and forty-two patients met study criteria. Fifty-four patients (38%) were platinum-sensitive. Comparing patients with relapse < 12 months and those with relapse > 12 months, a CA 125 level after 3rd NAC cycle < 35 UI/ml was significantly associated with improved overall survival (OS) and relapse-free survival (RFS). In the multivariate model including cytoreduction, cycle to nadir and CA 125 level after 3rd NAC cycle, patients with a CA 125 level after 3rd NAC cycle > 35 UI/ml had 3.8 times more at risk for relapse < 12 months (95% CI [1.7-8.5], p<0.001). Conclusions: The present study suggests that epithelial ovarian cancer patients who normalized their CA 125 level after 3rd NAC cycle, have a significantly longer RFS and OS. The CA 125 level after 3rd NAC < 35 UI/ml was an independent predictor for tumor platinum-sensitivity.
Prediction of reclassification at repeat biopsy with PSA and [-2]proPSA doubling time during active surveillance for low-risk prostate cancer: Prospective longitudinal analysis of a Japanese multicenter study cohort.
Authors: Hiromi Hirama, Mikio Sugimoto, Kazuto Ito, Taizo Shiraishi, Yoshiyuki Kakehi
Journal: Journal of Clinical Oncology (2014)

e16069 Background: Prostate-specific antigen (PSA) kinetics, such as PSA doubling time (PSADT), are used for prediction of tumor progression during active surveillance (AS) for favorable prostate cancer (PCa). The aim of this study is to evaluate whether PSADT, fPSA doubling time (fPSADT), p2PSA doubling time (p2PSADT) and phi (Prostate Health Index: (p2PSA/fPSA)×√tPSA) doubling time (phiDT) are associated with pathological findings in a Japanese prospective AS cohort. Methods: 134 men with T1cN0M0 PCa enrolled in the Japanese multicenter AS study between 2002 and 2003. 118 of 134 men opted AS as the initial strategy and they were checked PSA every 2 months for initial 6 months and every 3 months thereafter. The patients who remained on AS for 1-year were recommended to undergo repeat biopsy. In 67 patients who underwent repeat biopsy at 1-year after AS, we analyzed the relationship of biopsy reclassification in repeat biopsy with PSADT, fPSADT, p2PSADT and phiDT before repeat biopsy. Results: Reclassification rate was 37.3% (25/67). In the reclassification group, median PSADT, fPSADT, p2PSADT and phiDT were 3.58, 2.04, 1.32 and 1.39 years, respectively. In the non-reclassification group, median PSADT, fPSADT, p2PSADT and phiDT were 2.38, 1.59, 1.56 and 1.33 years, respectively. There were no statistical differences in PSADT, fPSADT, p2PSADT and phiDT between the two groups (Table). Conclusions: Our findings confirm that PSADT and p2PSADT could not be prediction markers of biopsy reclassification in patients with low-risk PCa managed by AS. Reclassification group (n=25) Non-reclassification group (n=42) p-value Collecting time of blood samples Median (range) 6 (5-8) 6 (5-7) ns tPSADT (year) Median (range) 3.58 (-118.45~13.27) 2.38 (-128.43~87.28) ns fPSADT (year) Median (range) 2.04 (-55.60~76.65) 1.59 (-41.45~58.75) ns p2PSADT (year) Median (range) 1.32 (-13.13~68.33) 1.56 (-18.76~48.79) ns phiDT (year) Median (range) 1.39 (-13.48~11.36) 1.33 (-266.12~24.78) ns
IgA vasculitis in adults: few certainties and many uncertainties
Authors: Alojzija Hočevar, Matija Tomšič, Žiga Rotar
Journal: Annals of the Rheumatic Diseases (2019)

We read with great interest the article on cardiovascular, thromboembolic and renal outcomes in patients with immunoglobulin A vasculitis (IgAV), published recently online in A nnals of the R heumatic D iseases .1 

Tracy et al , estimated both a childhood and an adult onset of IgAV incidence rates and reported an increased risk of hypertension and chronic kidney disease in patients with IgAV, compared with age-matched and sex-matched controls based on retrospective data over a 12-year period extracted from a primary care database in the UK. They estimated the incidence rate of adult IgAV at 2.2 per 100 000 person-years ,1 which is close to the historic belief that IgAV rarely affects adults but was …
Large cell neuroendocrine carcinoma of the urinary bladder: A pooled analysis.
Authors: Jue Wang
Journal: Journal of Clinical Oncology (2014)

e15521 Background: Neuroendocrine tumors (NETs) of the urinary bladder are rare, representing about 1% of all bladder cancers, and consist of typical and atypical carcinoid tumors, small cell carcinomas (SCCs), and large cell neuroendocrine carcinomas (LCNEC). This study evaluates the clinical characteristics, treatment, and survival of patients with LCNEC of the urinary bladder. Methods: A retrospective review of LCNEC of the urinary bladder patients at University of Nebraksa Medical Center between 1997 and 2010 was performed in conjunction with a systematic literature search for published articles on this disease. Descriptive statistics, such as frequency counts, medians, and ranges, were used to characterize the pooled sample. The survival rate was calculated using log-rank and Kaplan-Meyer analyses. Results: The final cohort for the study included 30 patients: five from UNMC and 25 patients from published cases. The median patient age was 68 years (20-85), with a male predominance. Of all 30 patients, 56% had pure LCNEC histology, while the remaining patients had mixed histology. All patients (100%) had muscle-invasive disease, and 40% of the patients initially had metastatic disease. Of the patients initially presented with having localized disease, the disease recurred in over half (55%) in one to 18 months. The most-common location of metastatic disease was in the lung (81.8%). In 80% of the cases, a radical or partial cystectomy was performed; 50% patients received chemotherapy. There was significant difference in the overall survival and recurrent-free survival rates between different tumor stages. Conclusions: LCNEC of the urinary bladder has an aggressive clinical course and is associated with poor prognosis. There is urgent need for early detection and the development of novel treatment options.
FOLFIRI3-aflibercept as second- or later-line therapy in patients with metastatic colorectal cancer.
Authors: Candice Carola, Francois Ghiringhelli, Stefano Kim, Thierry Andre, Juliette Barlet, Leila Bengrine, Helene Marijon, Marie Line Garcia, Christophe Borg, Linda Dainese, Nils Steuer, Annette K Larsen, Aimery De Gramont, Benoist Chibaudel
Journal: Journal of Clinical Oncology (2018)

817 Background: The efficacy of the standard FOLFIRI-aflibercept second-line therapy may be improved by the chemotherapy regimen in metastatic colorectal cancer (MCRC). FOLFIRI was optimized by splitting the dose of irinotecan on day 1 and day 3 and by removing the bolus of 5-FU in the FOLFIRI3 regimen. Methods: This is a retrospective multicentric cohort, evaluating efficacy and safety of the association of aflibercept with FOLFIRI3, in patients (pts) with previously treated MCRC. The primary endpoint was overall response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: From September 2014 to December 2016, 74 pts were treated in four French centers. Nine pts were excluded due to prior use of aflibercept (n = 3), more than one prior line of treatment in irinotecan-naïve pts (n = 3) and inadequate liver function (n = 3). In the cohort of irinotecan-naïve pts (n = 30), ORR and DCR were 43.3% and 76.7%. Median PFS and OS were 11.3 months (95% CI 6.1-29.0) and 17.0 months (95% CI 13.0-17.3). The most common ( &gt; 5%) grade 3-4 adverse events were diarrhea (37.9%), neutropenia (14.3%), stomatitis and anemia (10.4%), hypertension (6.7%). In the cohort of pts previously treated with irinotecan (n = 35), 20 (57.1%) pts received ≥2 prior lines of treatment with various prior irinotecan regimen (FOLFIRINOX, n = 21; FOLFIRI, n = 10; FOLFIRI3, n = 4). ORR and DCR were 34.3% and 60.0%. Median PFS and OS were 5.7 months (95% CI 3.9-10.4) and 14.3 months (95% CI 12.8-19.5). In 4 patients refractory to irinotecan, FOLFIRI3-aflibercept led to one partial response, 2 stabilizations, and one patient not evaluable. Conclusions: A minimal modification of the FOLFIRI regimen led to a dramatically improvement of efficacy with FOLFIRI3-aflibercept, whatever prior use of irinotecan. Further randomized trial is planned.
Knowledge, Cultural, and Structural Barriers to Thalassemia Screening in Migrant Populations in Thailand
Authors: Julia Z. Xu, Wilaslak Tanongsaksakul, Thidarat Suksangpleng, Supachai Ekwattanakit, Suchada Riolueang, Bonnie N. Kaiser, Nathan M. Thielman, Marilyn J. Telen, Vip Viprakasit
Journal: Blood (2018)
Cardiotoxicity and second malignant neoplasms associated with dexrazoxane in children and adolescents: A systematic review of randomized trials and nonrandomized studies.
Authors: Furqan Shaikh, Sarah Alexander, Lee Dupuis, Abha A. Gupta, Paul C. Nathan
Journal: Journal of Clinical Oncology (2014)

10093 Background: Several randomized controlled trials (RCTs) in breast cancer have demonstrated the efficacy of dexrazoxane (DRZ) in reducing anthracycline cardiotoxicity. However, research on DRZ in pediatric patients has been stalled by a recent report of increased second malignant neoplasms (SMN). The objective of this study was to systematically review the evidence for and against the use of DRZ in children. Methods: We searched Medline, Embase, Cochrane, and abstracts for all RCTs and non-randomized studies (NRSs) that compared DRZ to no cardioprotection among cancer patients <18 years of age receiving anthracyclines. Results: 23 articles reporting 5 RCTs (1,254 patients) and 11 NRSs (3,329 patients) were identified. Among 5 RCTs, there were 16/625 (2.5%) SMN with DRZ vs 6/619 (1.0%) SMN without DRZ (risk ratio (RR) 2.52, p=0.06, number needed to harm = 63). The types of SMN varied: two RCTs that used concurrent etoposide reported an increased risk of AML, while one RCT that used cranial radiation reported an increased risk of brain tumors. There was no significant difference in EFS (5 RCTs, p=0.93). Among 2 RCTs, DRZ was associated with an improved shortening fraction Z-score (mean difference (MD) 0.61, p=0.002) and thickness:dimension Z-score (MD 0.66, p<0.001). A significant effect on clinical cardiotoxicity could not be shown due to a very low cardiotoxic event rate (3 events among all RCT patients). Among NRSs, there were 6/860 (0.7%) SMN with DRZ vs 18/1,825 (1.0%) SMN without DRZ (p=0.58). DRZ was associated with a reduction in clinical cardiotoxicity (RR 0.29, p=0.001, NNT=14) and clinical+subclinical cardiotoxicity (RR 0.43, P<0.001, NNT=4). However, NRSs were subject to time-related bias, with control arms generally having longer follow-up. Conclusions: DRZ is associated with a significant reduction in cardiotoxicity in pediatric NRSs. Evidence of benefit from pediatric RCTs currently relates only to surrogate outcomes and is limited by a low clinical event rate. DRZ is associated with a statistically borderline increase in SMN, although an interaction with other carcinogenic treatments (radiation, etoposide) may be responsible.
Impact of excision repair cross-complementation group 1 (ERCC1) protein on survival of patients with osteosarcoma treated with cisplatin-based chemotherapy.
Authors: Kentaro Igarashi, Norio Yamamoto, Toshiharu Shirai, Katsuhiro Hayashi, Hideji Nishida, Hiroaki Kimura, Akihiko Takeuchi, Shinji Miwa, Hiroyuki Inatani, Shingo Shimozaki, Takashi Kato, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2014)

10535 Background: Excision repair cross-complementation (ERCC) genes encode proteins that participate in nucleotide excision repair, and these proteins are crucial for preventing DNA damage caused by cisplatin and its low expression correlates with better survival after cisplatin-based chemotherapy in several cancers. We retrospectively evaluated the relationship between expression of the excision repair cross-complementation 1 (ERCC1) protein and outcome in patients with osteosarcoma treated with cisplatin-based chemotherapy. Methods: Medical records and tissue samples from 105 patients with a histologically confirmed diagnosis of high-grade osteosarcoma previously treated with cisplatin-based chemotherapy (K2 protocol) were retrospectively analyzed. They were 61 males and 44 females with the mean age of 23.3 years (range 5–76). A Immunohistochemical staining of biopsy specimen was used to assess the expression of ERCC1. Results: Thirty-two (30%) samples were ERCC1-positive. Metastasis at diagnosis, chondroblastic subtype, poor response to chemotherapy, and positive ERCC1 expression were associated with poor event free survival (P = 0.044, P = 0.039, P = 0.003, and P = 0.001 respectively). Trunk location, metastasis at diagnosis, chondroblastic subtype, poor response to chemotherapy, and positive ERCC1 expression were associated with poor overall survival (P = 0.006, P < 0.001, P = 0.012, P = 0.018 and P < 0.001 respectively). Patients with an ERCC1-negative tumor had a significantly longer event-free survival (113.7 versus 55.5 months; P = 0.001) and overall survival (198.9 versus 99.6 months; P < 0.001) compared with the group positive for ERCC1. Multivariate analysis for event-free survival and overall survival confirmed that the absence of ERCC1 expression correlated with longer event-free survival (HR 2.297, 95% CI 1.284–4.106, P = 0.005) and longer overall survival (HR 3.220, 95% CI 1.329–7.800, P = 0.010). Conclusions: We confirmed that ERCC1 expression is predictive of outcome in osteosarcoma patients treated with cisplatin-based chemotherapy. Patients with ERCC1-negative tumors showed an increased survival rate.
Genomic, mRNA and miRNA profiling of malignant peripheral nerve sheath tumors
Authors: Leonardo Meza-Zepeda, Stine Kresse, Hege Ohnstad, Magne Skarn, Bodil Bjerkehagen, Ola Myklebost
Journal: Cancer Research (2007)

2971  Human sarcomas, malignant tumors of mesenchymal origin, show recurrent copy number alterations of specific chromosomal segments. In order to identify novel alterations and target genes for the copy number changes, we have constructed a genomic microarray with bacterial- and P1 artificial chromosome (BAC and PAC) clones covering the human genome at 1 Mb resolution, as well as the 1q12-q25 region at high resolution (tiling-path). We have used this genomic microarray for array comparative genomic hybridization (array CGH) of a panel of 170 human sarcomas.  Malignant peripheral nerve sheath tumors (MPNSTs) arise sporadically or as part of the neurofibromatosis type 1 (NF1) or -2 (NF2) autosomal inherited disorders. We have analyzed seven MPNSTs, and correlated DNA copy number changes to patient outcome. A segment of 17q was gained in all patients who died of cancer.  In order to identify candidate genes with increased expression in 17q, we have expression profiled six of the seven samples analysed by array CGH. Results show a number of known and novel genes with increased expression and functions relevant to cancer biology. In addition, seven known miRNAs are located in the differentially amplified area. Using Exiqon miRNA microarrays and Taqman assays we are investigating their expression.  In addition, the impact of DNA copy number alterations will be correlated to mRNA and miRNA expression genome-wide.  This and previous work shows the potential use of array CGH to distinguish patients with different clinical outcome, although further validation is required on larger tumor panels.
Impact of perioperative chemotherapy on Nigerian patients with locally advanced and metastatic gastric cancer.
Authors: Olusegun Isaac Alatise, Adewale O Adisa, Olukayode Adeolu Arowolo, Akinbolaji Andrew Akinkuolie, Olusegun Adekanle, Olukayode O Lawal, Augustine Agbakwuru, Abdulrusheed Kayode Adesunkanmi
Journal: Journal of Clinical Oncology (2014)

e15180 Background: The overall 5-year survival of patients with gastric cancer is only 14% in Nigeria as compared to 23% in the United States of America and 60% in Japan [1-3]. The possible reasons include late presentation and unavailability of adjunctive therapy such as chemotherapy. Systemic therapy had been shown to improve survival in advanced or metastatic disease. The current study aimed at assessing the impact of perioperative adjuvant chemotherapy on the overall survival of patient with advanced gastric cancer. Methods: Patients with advanced gastric cancer from January 2008 to December 2013 at Obafemi Awolowo University Teaching Hospitals complex were recruited to the study prospectively. The patients with resectable disease had surgery and adjuvant chemotherapy. While patients with irresectable disease had neo-adjuvant chemotherapy. The NCCN guideline combination therapy prescribe doses of Epirubicin, Cisplastin and 5-Fluorouracil (ECF) was used. Combination of Docetaxel, Cisplastin and 5-Fluorouracil (DCF) was used in case of resistance. Results: During the study period, 72 patients had gastric cancer, of which 66 (91.7%) had distal (DGC) and 8 (8.3%) had proximal gastric cancer (PGC). Only 33 (45.8%) patients had resectable disease at presentation (32 DGC and 1PGC). Out of the 34 patients with unresectable DGC, 15 could not afford chemotherapy. The mean survival in those that had chemotherapy was 9.2 months while those that could not afford it was 5.6 months. Curative surgery was offered to all patients that had resectable diseases. One patient died at perioperative period. After 2 year follow up, the overall survival was 25/32 (78.1%). 5/32 had features of recurrence at 2 year follow up. Those that had recurrence were placed on second line, but only 2 can afford the drug. Tolerability of the DCF was however poor. Conclusions: Perioperative chemotherapy in patients with metastatic and locally advanced gastric cancer significantly increase the survival in Nigerian patients. We hereby suggest regular use of this in the management of gastric cancer.