tbuckley/cabot-search huggingface dataset:
Neuroendocrine tumors of the gastroenteropancreatic system (NET-GEP). Correlation between Ki-67 immunostaining, histological features and clinical behaviour
Authors: S. A. Szyldergemajn, J. O’Connor, G. Mendez, M. Chacón, M. Barugel, F. Marmissolle, M. Amat, E. Domenichini, E. Roca
Journal: Journal of Clinical Oncology (2005)

4192 Background: There is a marked increase in the diagnosis of NET-GEP. This group of tumors are of a remarkable heterogeneity and consensus and recommendations for the management of these patients(pts)still lacks. It was proposed that Ki-67 immunostaining, could be an important aid to further define aggressiveness of the disease, the need for early therapies and treatment modalities (Öberg, ASCO 2002). Methods: We studied, retrospectively, biopsies obtained between 1995–2003 from pts with NET-GEP followed in our centers,included in a clinical database. We analyzed classical morphologic features of these biopsies. With standard immunohistochemistry (IHC) test (Mib-1) we stablished the cellular proliferation index (S phase). Based in clinical data we defined indolent vs aggressive clinical behaviour. Results: From our database we selected 31 pts with available biopsies, 15 were men, median age: 48 years (r 14–76), median number of treatments:2 (r 1–4), primary localization: pancreatic 3 pts, gastric 3, small bowel 10, appendix 2, colorectal 5 and unknown 8. In 9 pts (29%) the initial diagnoses was erroneously different from NET-GEP. Twenty-one pts has metastastic disease at diagnoses, most of them with liver involvement. In 23/31 pts (74%) have had positive staining with TTF-1. Conclusions: We found correlation between aggressive clinical behaviour, poor differentiated histology and high cellular proliferation index. The level of Ki-67 was accurely correlated with aggressive or indolent behaviours in the pts with poor differentiate histology. The high proportion of TTF-1 + IHC is a remarkable observation. Although this is a small retrospective study, the results allowed us to think that knowing 3 factors: clinical behaviour, histology and Ki-67 staining could be helpful in decision making process. This hypothesis should be tested in prospective trials. No significant financial relationships to disclose.
Classification of low quality cells from single-cell RNA-seq data
Authors: Tomislav Ilicic, Jong Kyoung Kim, Aleksandra A. Kolodziejczyk, Frederik Otzen Bagger, Davis James McCarthy, John C. Marioni, Sarah A. Teichmann
Journal: Genome biology (2016)

Single-cell RNA sequencing (scRNA-seq) has broad applications across biomedical research. One of the key challenges is to ensure that only single, live cells are included in downstream analysis, as the inclusion of compromised cells inevitably affects data interpretation. Here, we present a generic approach for processing scRNA-seq data and detecting low quality cells, using a curated set of over 20 biological and technical features. Our approach improves classification accuracy by over 30 % compared to traditional methods when tested on over 5,000 cells, including CD4+ T cells, bone marrow dendritic cells, and mouse embryonic stem cells.
Efficacy of Enzalutamide (Enza) Following Abiraterone Acetate (Abi) in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer (Mcrpc) Patients (Pts)
Authors: A.A. Azad, B.J. Eigl, N. Murray, C.K. Kollmannsberger, K.N. Chi
Journal: Annals of Oncology (2014)
Magnitude of benefit of the addition of bevacizumab (BEVA) to first-line chemotherapy (CT) for advanced/metastatic colorectal cancer (MCRC): Meta-analysis of randomized clinical trials
Authors: V. Vaccaro, F. Cuppone, F. Loupakis, M. Milella, P. Carlini, C. Nisticò, A. Falcone, E. Terzoli, F. Cognetti, E. Bria
Journal: Journal of Clinical Oncology (2009)

e15021 Background: The monoclonal antibody against vascular endothelial growth factor BEVA has recently demonstrated to improve survival for MRC patients (pts). Nevertheless, the magnitude of the provided benefit in the daily practice is still controversial. In order to quantify the benefit of adding BEVA to CT for MCRC, a literature-based meta-analysis was conducted. Methods: Survival Hazard Ratios (HR) were extracted from prospective, randomized clinical trials (RCTs, either phase II/III) reports. HR and event-based relative risks (RR) with 95% confidence intervals (CI) were derived through a random-effect model. Differences in primary (progression-free- and overall-survival, PFS/OS) and secondary outcomes (overall, partial and complete response rates, ORR/PR/CR) were explored. Absolute differences (AD) and the number of patients needed to treat (NNT) were calculated. Heterogeneity test and a meta-regression analysis with clinical predictors for outcomes were conducted as well. A sensitivity analysis according to the trial phase-design was accomplished. Results: Five trials (2,728 pts), 2 phase II (313 pts) and 3 phase III (2,415 pts), were gathered. No significant interaction was found in the sensitivity analysis between phase II and III, although a trend showed a better PFS results for BEVA in phase II trials (p=0.057). At the meta-regression analysis female gender and rectal primary site were significant predictors for PFS (p=0.003, p=0.005). Toxicity analysis is ongoing. Conclusions: Although concerns regarding costs and toxicities still exist, BEVA significantly improves the outcome of untreated MCRC pts. The absolute benefit provided into an unselected population for molecular features should be considered of paramount importance for advanced disease. [Table: see text] No significant financial relationships to disclose.
A pilot multicenter phase II study of adjuvant docetaxel (D) for high risk prostate cancer (PC) patients (pts) after radical prostatectomy (RP): Preliminary data
Authors: E. Rosenbaum, A. Kibel, B. Roth, G. Wilding, R. Dreicer, G. Chatta, D. Petrylak, R. S. Dipaula, T. M. Beer, M. Eisenberger
Journal: Journal of Clinical Oncology (2005)

4565 Background: We conducted a pilot adjuvant D study in pts at high risk for recurrence after RP. Study objectives were to evaluate: 1. toxicity 2. feasibility of 6 months of adjuvant D treatment and 3. Incidence of PSA relapses (>0.2ng/ml) in 2 and 3 years (vs. matched controls). Methods: Eligible pts had confirmed PC, within 3 months of RP, without distant metastases, organ dysfunction or prior RT or systemic treatment. Pathology was centrally reviewed (JHU). Risk was assessed based on a multivariate Cox proportional hazards model (Rw' = lymph node (0/1)*1.43 + seminal vesicle (0/1)*0.51 + surgical margin (0/1)*1.15 + modified Gleason score (MGS) (0–4) * 0.71) [MGS: Gleason 5=0; 3+3=1; 3+4=2; 4+3=3; 8–10=4]. The minimum value for study entry was based on a projected 50% rate of recurrence by 3 years = Rw' > 2.84. (Roberts et al Urology 2001). Treatment included 6 cycles of IV D 35mg/m2 on days 1, 8, 15 of a 28 day cycle starting 4–12 weeks after surgery. We have 90% power to detect a 3-year progression free survival rate of 69% versus the control rate of 50%, α=0.05. Results: 77 pts with a median age of 60(43–76) and median Rw' of 4.07 (2.85–5.93) were enrolled (4/02–1/04). Treatment was well tolerated and all pts completed treatment. Hyperglycemia was the only grade IV toxicity (2.6%). Grade III: hyperglycemia 7.7%, dyspnea 5.2%, leukopenia 3.9%. 5 pts required dose reduction (LFT's), and 6 Rx delay. One death probably unrelated to D. Grade I/II (>30%) included the common D toxicities being mostly mild and reversible. With a median f/u of 17m (10–31), the median time to PSA relapse was not reached. 3 pts developed distant metastases and 2 pts died from progressive disease. Comparison of outcome with pathologically and clinically matched historical controls (JHU) is needed and is currently in progress and ongoing. Conclusions: These data suggest that post operative adjuvant weekly D is feasible, well tolerated and has only moderate reversible toxicity. Based on recent reports of improved survival with D in HRPC, further evaluation of D (and hormonal therapy) in a phase III in the adjuvant setting is warranted. (Supported by Aventis). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Final analysis of COMET-2: Cabozantinib (Cabo) versus mitoxantrone/prednisone (MP) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) with moderate to severe pain who were previously treated with docetaxel (D) and abiraterone (A) and/or enzalutamide (E).
Authors: Ethan M. Basch, Mark C. Scholz, Johann Sebastian De Bono, Nicholas J. Vogelzang, Paul L. De Souza, Gavin M. Marx, Ulka N. Vaishampayan, Saby George, James K. Schwarz, Emmanuel S. Antonarakis, Joe M. O'Sullivan, Arash Rezazadeh Kalebasty, Kim N. Chi, Robert Dreicer, Thomas E. Hutson, Milan Mangeshkar, Jaymes S. Holland, Aaron Weitzman, Howard I. Scher
Journal: Journal of Clinical Oncology (2015)

141 Background: Cabo inhibits tyrosine kinases including MET and VEGFRs. In a phase 2 study in mCRPC pts, Cabo was associated with improvements in pain, bone scans, measurable disease, and circulating tumor cells. COMET-2 compared the effects of Cabo versus MP on pain palliation in men with progressive mCRPC. Methods: In this double-blind, controlled phase 3 study (NCT01522443), pts with moderate to severe pain and disease progression following D, and A and/or E were randomized 1:1 to receive Cabo (60 mg qd) or MP (12 mg/m 2 q3wk and 5 mg bid, resp). All pts were required to have a 7-day average of 4+ pain per Brief Pain Inventory (BPI) item 3 while on an optimized narcotics regimen at baseline. Randomization was stratified by prior cabazitaxel and ECOG performance status. The primary endpoint was pain response (≥30% reduction in BPI item 3) at week 6, confirmed at week 12, without increase in narcotics. The original sample size (N = 246) was selected to achieve at least 90% power to detect an increase in pain response with Cabo (25%) vs. MP (8%) using a two-sided α = 0.05 chi-squared test. The secondary efficacy endpoints were bone scan response (BSR) and overall survival (OS). Results: 119 pts were randomized between March 2012 and July 2014. Randomization was concluded prior to reaching the planned sample size because the companion study COMET-1 did not show a significant OS benefit compared to P in a similar population. Pain response rates were 15% for Cabo vs 17% for MP (P = 0.773). BSR rates were 31% for Cabo vs 5.2% for MP. Median OS was 9 months for Cabo vs 7.9 months for MP. Most frequent G3/4 AEs in the Cabo arm were anemia (22% vs 26% MP), hypertension (22% vs 0% MP), fatigue (18% vs 8.8% MP), and AST increased (10% vs 1.8% MP), with fewer pts discontinuing study treatment for AEs in the Cabo arm (16% vs 26% MP). Conclusions: The primary endpoint of improving pain response was not achieved in this heavily pretreated population. The key secondary endpoints of BSR and OS showed trends favoring the Cabo arm, and no new safety signals were observed at the dose of 60 mg. Clinical trial information: NCT01522443.
Expression of Fcγ Receptors on a Subpopulation of Nonlymphoid Tumor Cells and Its Enrichment2
Authors: Maya Ran, Zahava Dux, Romema Anavi, Isaac P. Witz
Journal: JNCI Journal of the National Cancer Institute (1984)

Nonadherent Fcγ receptors (FcγR) expressing cells from SEYF-a tumors that form rosettes with sheep erythrocytes coated with IgG antibodies (EA) were isolated by Percoll density gradients. The EA-IgG rosette-forming cells were characterized by the parameters of 1) binding of IgG immune complexes; 2) binding of purified monoclonal antibodies against mouse FcR; 3) sensitivity to complement-dependent lysis mediated by syngeneic anti-SEYF-a antibodies; 4) expression of parental H-2 antigen when grown in F1 hybrids; 5) incorporation of [125I]5-iodo-2'-deoxyuridine; and 6) growth in syngeneic mice. The nonadherent EA-IgG rosette-forming cell population was found to be composed of both host lymhpocytes as well as of tumor cells. Tumor-seeking lymphocytes then were removed from SEYF-a tumors by velocity sedimentation on Percoll. The remaining cell population was tumorigenic and expressed FcR, as well as tumor antigens. These tumor EA-IgG rosette-forming cells exhibited a very low rate of DNA synthesis compared with that of nonrosetting tumor cells.
Symptom interference with quality of life (QoL) in advanced solid tumors and hematological malignancies
Authors: A. A. Novik, T. Ionova, A. Kishtovich, S. Kaliadina, D. Fedorenko, I. Rikov
Journal: Journal of Clinical Oncology (2005)

8202 Introduction: Patients with advanced cancer experience impaired QoL due to symptoms related to the disease itself and to treatment toxicity. We have developed the following grades of QoL impairment as compared to a population norm (PN): mild (25% decrease from a PN), moderate (25–50% decrease), severe (50–75% decrease) and critical (>75% decrease). Understanding of symptom interference with a patient’s QoL provides the basis for better cancer outcome measurement. The goal of research was to study the most prevalent symptoms in patients with advanced solid tumors (ST) and hematological malignancies (HM) with different grades of QoL impairment. Patients and Methods: 201 advanced cancer patients: 119 ST and 82 HM (male/female 80/121; mean age 61.5) were enrolled in the study. To compare with controls a gender- and age-adjusted sample from the St.Petersburg population norm was used. SF-36 and M.D. Anderson Symptom Inventory were used for patient-reported outcomes assessment. To obtain QoL Index the Integral profile method was used. Results: The majority of patients with ST and HM experienced critical (40 and 44%, respectively) and severe (21 and 20%, respectively) QoL impairment. Moderate and mild QoL impairment was observed in about 10 and 12% of patients in both groups. About 16% of patients had no QoL impairment. The QoL indices differed significantly depending on the grade of QoL impairment (p=0.00002). The most severe symptom was fatigue (prevalence of 95%) in both groups. Sleep disturbance was present in two thirds of patients. 60 and 75% of patients with HM and ST, respectively, experienced pain. Moderate -to- severe levels of symptoms led to critical and severe QoL impairment. Severe symptoms resulted in a critical decrease in QoL. Conclusion: The majority of patients with advanced ST and HM exhibit critical and severe QoL impairment as compared to a population norm. They experience moderate-to-severe fatigue, pain, or sleep disturbance. Grading of QoL impairment and analysis of symptom burden is worthwhile to provide adequate management of advanced cancer. No significant financial relationships to disclose.
Nucleotide sequence analysis of the human salivary protein genes HIS1 and HIS2, and evolution of the STATH/HIS gene family.
Authors: L M Sabatini, T Ota, E A Azen
Journal: Molecular Biology and Evolution (1993)

Human histatins are a family of low-M(r), neutral to very basic, histidine-rich salivary polypeptides. They probably function as part of the nonimmune host defense system in the oral cavity. A 39-kb region of DNA containing the HIS1 and HIS2 genes was isolated from two human genomic phage libraries as a series of overlapping clones. The nucleotide sequences of the HIS1 gene and part of the HIS2(1) gene were determined. The transcribed region of HIS1 spans 8.5 kb and contains six exons and five introns. The HIS1 and HIS2(1) genes exhibit 89% overall sequence identity, with exon sequences exhibiting 95% identity. The two loci probably arose by a gene duplication event approximately 15-30 Mya. The HIS1 sequence data were also compared with that of STATH. Human statherin is a low-M(r) acidic phosphoprotein that acts as an inhibitor of precipitation of calcium phosphate salts in the oral cavity. The HIS1 and STATH genes show nearly identical overall gene structures. The HIS1 and STATH loci exhibit 77%-81% sequence identity in intron DNA and 80%-88% sequence identity in noncoding exons but only 38%-43% sequence identity in the protein-coding regions of exons 4 and 5. These unusual data suggest that HIS1, HIS2, and STATH belong to a single gene family exhibiting accelerated evolution between the HIS and STATH coding sequences.
Immunophenotypic diversity and prognosis of adult T-cell leukemia/lymphoma
Authors: A. Carrasco, B. Beltran, J. Malaga, G. Ferrel, H. Rios, J. Castillo, J. Huamani, M. Rodriguez, D. Flores, S. Falcon
Journal: Journal of Clinical Oncology (2006)

17565 Background: Adult T-cell leukaemia/lymphoma (ATLL) is an aggressive disease associated with human T-cell lymphotropic virus type-I (HTLV-I) with heterogeneous clinical presentation and outcomes, described in Southern Japan, Europe, Caribbean and previously on Pacific coast of South America including Peru (EHA 2001, abst. 304). Shimoyama’s ATLL classification (BHJ 1991:79), includes four types: acute, lymphomatous, chronic and smouldering; recently a new clinical cutaneous type had been described (BJD 2005:152). Methods: We described our experienced previously (ASH 2005, abst. 4797). Herein we analyzed immunophenotypically our ATLL patient population by flow cytometry looking for aberrant phenotypes and their correlation with overall survival. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: From July 1997 to March 2005 our registry had 69 cases, 37 had flow pre-treatment: acute type (n = 31) and lymphomatous (n = 6). Over our 37 flow done we were able to analysis only 33. The incidence of the typical (CD4+/CD8-) phenotype, the double-negative (CD4-/CD8-), the double-positive (CD4+/CD8+), and the CD8 positive (CD4-/CD8+) phenotypes was 58%, 12%, 15%, and 12% respectively. The median overall survival (OS) for the 33 patients was 4.1 months (range: 0.5–46.1). The patients with typical phenotypes had a median OS of 4.1 months better than the patients with the double-negative phenotype whom median OS was 2.0 (range: 1.5–9.7) but not significant. Median OS in the double positive and the CD4-/CD8+ phenotype population were 15.2 and 4.8 months respectively with no significance Conclusions: ATLL has a diversity of immunophenotype, our data suggest that there is not any correlation with survival, major accrual will gave us a final conclusion. No significant financial relationships to disclose.
Phase I/II results of a second-generation humanized anti-CD20 antibody, IMMU-106 (hA20), in NHL
Authors: F. Morshhauser, J. P. Leonard, B. Coiffier, M. Petillon, M. Coleman, A. Bahkti, N. Teoh, W. A. Wegener, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2006)

7530 Background: The humanized anti-CD20 antibody, IMMU-106 (hA20), has similar murine CDRs to rituximab, but the remaining framework is identical to humanized anti-CD22 IgG1 antibody, epratuzumab, whose safety and short infusion times have been reported. Methods: An open-label, multicenter, phase I/II, dose escalation study was conducted in adult patients with recurrent NHL to establish the safety, tolerance, PK, and immunogenicity (HAHA) of hA20 administered weekly x 4. Thirty-four patients have now received hA20 at 120 (n = 7), 200 (n = 6), 375 (n = 18) or 750 mg/m 2 (n = 3). These were predominantly stage III/IV patients (n = 27) with follicular lymphoma (N = 23) who received 1–7 prior treatments (median, 2), including 1 (N = 22) or more (N = 9) rituximab regimens (without progression within 6 months). Results: Thirty-three patients completed all 4 hA20 infusions. Median infusion times at 375 mg/m 2 were 3.1 h for 1st infusion, 2.0–2.3 h for subsequent infusions, and were generally shorter at lower doses. Fourteen patients (14%) had transient events, predominantly grade 1–2 events at 1st infusion. Antibody levels increased with hA20 dose; at 375 mg/m 2 , mean serum half-lives after 1st and 4th infusions were 3.4 ± 1.7 and 12.3 ± 3.9 days, respectively. With median follow-up now 3–6 months, peripheral blood B-cell depletion persists, HAHA evaluations are negative, and 14/23 patients (61%) with response assessments have objective responses by Cheson criteria. All 6 CR/CRu’s (23%) were in follicular lymphoma, occurred at all dose levels even at 120 mg/m 2 (including patients with 2–4 prior rituximab-containing regimens ), and with 5/6 continuing. Conclusions: The tolerability, relatively short infusion times, and CR/CRu’s in patients with follicular lymphoma who relapsed after rituximab-containing regimens is encouraging. This study is continuing to assess response durability and to determine the optimal hA20 dose for subsequent studies. [Table: see text]
Hypersensitivity reactions to teniposide (VM-26): an analysis.
Authors: P J O'Dwyer, S A King, C L Fortner, B Leyland-Jones
Journal: Journal of Clinical Oncology (1986)

An analysis of hypersensitivity reactions to teniposide was approached using three methods: investigator survey, adverse drug reaction analysis, and literature search. By the survey method, hypersensitivity incidence was 6.5% with the majority of the reactions (82%) occurring in brain tumor or neuroblastoma patients. By the second method, 43 cases of hypersensitivity that were reported to the National Cancer Institute (NCI) between January 1983 and October 1985 were analyzed in detail. Reaction onset was unpredictable according to the number of drug doses. The majority of the patients (65%) experiencing the reaction had neuroblastoma or brain tumors, and these patients also tended to react earlier in the course of drug administration than those with hematologic malignancies. Clinical presentation was not correlated with the patient's diagnosis. All patients recovered. However, only six of 13 were successfully rechallenged with the drug. The third approach, the literature search, provided information on 82 hypersensitivity reactions among 2,250 patients (3.6% incidence). Forty-five percent of these reactions were linked to neuroblastoma or brain tumor patients. The analysis of hypersensitivity to teniposide by these three methods provides insight into the true incidence of hypersensitivity reactions in the general patient population. The frequency of the reactions is substantially higher in patients with neuroblastoma and brain tumors. This population should be considered for future trials of aggressive prophylactic therapy.
Effect of Injected Frog-Kidney Tumor Extracts on Development of Tumors Under Promoting Conditions&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Keen A. Rafferty, Jr.
Journal: JNCI Journal of the National Cancer Institute (1963)

Previous reports indicated that Lucke kidney tumors occurred spontaneously with an incidence of 35 to 50 percent when Vermont Rana pipiens were maintained for 35 weeks under the tumor-promoting conditions of large body size and high environmental temperature. However, workers reporting group differences in tumor incidence related to injection of tumor extracts had in all instances used conditions in some way favoring low incidences of spontaneous tumor formation. In this report, results of injected tumor extracts in frogs kept under promoting conditions are given. The rate of tumor formation in frogs given injections was somewhat accelerated for several months, but both experimental and control groups eventually reached the same incidence. These findings are discussed in the light of the presumed viral nature of the Lucké tumor.