tbuckley/cabot-search huggingface dataset:
Radiation Recall Dermatitis With Concomitant Dabrafenib and Pazopanib Therapy
Authors: Sigurdis Haraldsdottir, Erin Bertino, Karl Haglund, Benjamin Kaffenberger, Manisha H. Shah
Journal: JAMA Dermatology (2016)

with 6 cycles of rituximab and ibrutinib.On this regimen, the patient's penile ulcer improved substantially.A repeated PET-CT scan 4 months later demonstrated resolution of FDG activity.Discussion | Lymphoma of the penis is extremely rare, with only 33 cases reported in the literature. 4 The most common subtype is DLBCL. 4 The differential diagnosis includes sexually transmitted infections, invasive fungal disease, vasculitis, trauma, and squamous cell carcinoma.A full medical history, physical examination, biopsy, and comprehensive histologic evaluation coordinated by experienced dermatopathologists and hematopathologists are required to reach the correct diagnosis.With regard to RT, therapeutic options are constantly evolving.However, treatment remains challenging, and prognosis remains poor.Current guidelines recommend treatment with (1) rituximab and hyper-cyclophosphamide-vincristinedoxorubicin-dexamethasone (hyper-CVAD) or (2) ibrutinib paired with a cell-cycle pathway inhibitor or intensive chemotherapy-immunotherapy. 1 Median survival is estimated at 5 to 8 months.
Gaq signaling is required for the maintenance of MLL-AF9-induced acute myeloid leukemia
Authors: J R Lynch, H Yi, D A Casolari, F Voli, E Gonzales-Aloy, T K Fung, B Liu, A Brown, T Liu, M Haber, M D Norris, I D Lewis, C W E So, R J D’Andrea, J Y Wang
Journal: Leukemia (2016)
The Helicobacter pylori
Authors: G D Bell
Journal: Gut (2001)

The Helicobacter pylori Handbook, 2nd edn. RV Heatley (Pp 64; illustrated; £12.95). UK: Blackwell Science Ltd, 1998. ISBN 0-632-05176-0.

In his preface, Dr Heatley states “Having been involved in the production of one of the established texts on this subject, and also having contributed to others, I have written this book with the generalist in mind. It is intended mainly for those in primary care but, hopefully will also be of value to many in other disciplines including hospital specialities not principally involved with H pylori management, including those in care of the elderly patients, paediatrics, general bacteriology, …
Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome
Authors: Daniela A Braun, Carolin E Sadowski, Stefan Kohl, Svjetlana Lovric, Susanne A Astrinidis, Werner L Pabst, Heon Yung Gee, Shazia Ashraf, Jennifer A Lawson, Shirlee Shril, Merlin Airik, Weizhen Tan, David Schapiro, Jia Rao, Won-Il Choi, Tobias Hermle, Markus J Kemper, Martin Pohl, Fatih Ozaltin, Martin Konrad, Radovan Bogdanovic, Rainer Büscher, Udo Helmchen, Erkin Serdaroglu, Richard P Lifton, Wolfram Antonin, Friedhelm Hildebrandt
Journal: Nature Genetics (2016)
Stability <italic>In Vitro</italic> of Diverse Capacities for Tumor Production and Glucose Metabolism in Three Murine Clones Derived From the Same Cell
Authors: Katherine K. Sanford, Mark W. Woods, Dwight B. McNair Scott, Harold A. Kerr
Journal: JNCI Journal of the National Cancer Institute (1969)

In a previous study on clones of mouse tissue-culture cells that had undergone neoplastic conversion in vitro, a positive correlation was noted between the capacity of the cells to grow as malignant neoplasms in vivo and their glycolytic activities as measured manometrically in vitro. Subsequent to that study, three of these clones, derived in vitro from the same cell, were adapted to protein-free chemically defined medium. The three clones after 5–8 years of culture in serum-containing medium and the derived strains in chemically defined medium were reexamined to see if their diverse capacities for tumor production and glucose metabolism were stable and correlated properties. In five of the six clones or strains a remarkable stability was noted. The one exception in chemically defined medium had retained a low glycolytic activity but showed an increased tumor-producing capacity that may have been associated with changes in antigenicity. Certain of the glucose oxidation enzymes of the three strains in chemically defined medium had also remained fairly stable in activity as compared with the earlier assays on the clones in serum-containing medium.
Mutations of HER2 gene in HER2-positive metastatic breast cancer
Authors: T. Prempree, C. Wongpaksa
Journal: Journal of Clinical Oncology (2006)

13118 Background: HER2 status of Breast Cancer has been assessed by IHC and FISH and used for therapeutic decision with a high degree of success. However, there were numbers of HER2-positive MBC who finally failed the Trastuzumab treatment after initial good response. Mechanisms of intrinsic and acquired Trastuzumab resistance are not yet known. Our Objective is to identify factor or factors responsible for Trastuzumab resistance. Methods: DNA extraction and Sequencing of HER2 gene were performed on primary tumors of HER2-positive 14 MBC patients undergoing Trastuzumab therapy. Re-biopsy were done on new metstatic sites of those cases discovered to have Trastuzumab resistance. Results: Of 14 MBC cases whose tumors showing positive IHC and FISH, there were no mutation found in their HER2 gene, exons 18,19, 20 and 21. However, 3 of 14 cases of MBC undergoing continuous Trastuzumab therapy with excellent response for more than one year, developed the resistance. All three cases had new metstatic sites biopsied, and showed D880N and E837Y mutations in the exon 21 of their HER2 genes. All three cases showed no response to trastuzumab therapy. Conclusions: 1) HER2-positive MBC tumors did not have any HER2 gene mutations in them. 2) Mutations arised in their HER2 gene, exon 21 may be responsible for the intrinsic and acquired Trastuzumab resistance. Additional work in this area is needed to further substantiate our findings. No significant financial relationships to disclose.
Comparison of the Sensitivity of Normal Hematopoietic and Transplanted Lymphoma Colony-Forming Cells to Chemotherapeutic Agents Administered &lt;italic&gt;In Vivo&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W R Bruce, B E Meeker, F A Valeriote
Journal: JNCI Journal of the National Cancer Institute (1966)
Final results of a phase 3, randomized, open-label study of darbepoetin alfa 200 mcg every 2 weeks (Q2W) versus epoetin alfa 40,000 U weekly (QW) in patients with chemotherapy-induced anemia (CIA)
Authors: J. Glaspy, R. Berg, D. Tomita, G. Rossi, S. Vadhan-Raj
Journal: Journal of Clinical Oncology (2005)

8125 Background: CIA is widely treated in the US with darbepoetin alfa (DA; Aranesp) or epoetin alfa (EA). This phase 3, noninferiority trial compared efficacy and safety of EA and DA using common doses and schedules used in US clinical practice. Methods: Eligibility criteria include non-myeloid malignancy with >8 weeks of planned chemotherapy (ctx), anemia (Hb ≤11g/dL), ≥18 years of age, ECOG performance status 0–2, and adequate renal/liver function. Pts were randomized 1:1 to DA 200 mcg Q2W or EA 40,000U QW stratified by screening Hb category (<10.0g/dL and ≥10.0g/dL) and planned ctx type (platinum vs non-platinum). Pts were treated up to 16 weeks with identical dose adjustment rules. The primary endpoint was the incidence of transfusion (tfn; Kaplan-Meier estimate) from day 29 to the end of treatment (EOT); a noninferiority margin of 11.5% was prespecified and based on published data for EA compared to placebo. Results: Of 1220 pts randomized, 1209 received ≥1 dose of study drug. Most pts were women (68%)and white (83%); 49% were ≥65 yrs old. The most common tumors were lung (26%), breast (21%), and GI (18%), and most pts had stage 3 or 4 disease (76%). At baseline, 36% of pts had Hb <10g/dL and 42% were to receive platinum ctx. Between day 29 and EOT, 21% of DA pts received a RBC tfn compared with 16% of EA pts, with the upper limit of the 95% CI <11.5%; similar results were observed for the per protocol analysis, with a difference of 3.8% (95% CL: -2.0, 9.7) between groups. Other prespecified analyses are below. The adverse event profile was similar for both groups. Conclusions: Non-inferiority with respect to tfn was demonstrated between DA 200 Q2W compared with EA 40,000 QW in a large, randomized phase 3 study. Similar efficacy was seen for Hb, PRO and safety endpoints. Less frequent dosing of darbepoetin alfa offers potential benefits for pts, caregivers, and healthcare providers. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen
Correction: Drugs, Diagnostic Tests Approved Quickly
Journal: Cancer Discovery (2011)

doi: 10.1158/2159-8290.CD-11-0299 ©2011 American Association for Cancer Research. Published OnlineFirst November 22, 2011. In this article (Cancer Discovery 2011;1:371), which was published in the October 2011 issue of Cancer Discovery (1), the agent later named crizotinib was incorrectly referred to as PLX4032 rather than PF-02341066. The online version of the article has been corrected and therefore no longer matches the print version. The author regrets the error.
First-in-human, phase I, dose-escalation study of selective PI3Kα isoform inhibitor MLN1117 in patients (pts) with advanced solid malignancies.
Authors: Dejan Juric, Johann Sebastian De Bono, Patricia LoRusso, John J. Nemunaitis, Elisabeth I. Heath, Eunice Lee Kwak, Teresa Macarulla, Elena Geuna, Maria Jose de Miguel Luken, Chirag Patel, Keisuke Kuida, Serap Sankoh, Fabian Zohren, Yaping Shou, Josep Tabernero
Journal: Journal of Clinical Oncology (2015)

2501 Background: PI3K signaling is aberrantly activated in many solid tumors; isoform-selective targeting may enable robust inhibition of this pathway in PIK3CA mutant tumors while sparing signaling in normal tissues. This study (NCT01449370) evaluated the safety, MTD, preliminary antitumor activity and pharmacokinetics/pharmacodynamics (PK/PD) of an investigational PI3Kα isoform-selective inhibitor, MLN1117. Methods: Pts age ≥ 18 with advanced solid tumors (except primary brain tumors) and known PIK3CA mutation status received oral MLN1117 once daily (QD, 100–300 mg) or 3 days per wk (MWF, 200–1200 mg, or MTuW, 200–900 mg) in 21-d cycles. Dose escalation proceeded via a 3+3 design based on cycle 1 (C1) DLTs. Plasma concentrations of MLN1117 for PK analyses were evaluated in C1. PI3K pathway biomarkers were assessed in skin biopsies via immunohistochemistry. Results: At data cut-off, 76 pts had enrolled; 24/29/23 pts to QD/MWF/MTuW schedules; median of 3 cycles per group. C1 DLTs occurred in: 2 QD pts (ALT/AST elevation), 4 MWF pts (ALT/AST elevation, hyperosmolar state, nausea, vomiting, diarrhea, dehydration, hyperglycemia and anorexia), and 1 MTuW pt (nausea). MLN1117 MTDs were 150 mg QD and 900 mg for MWF/MTuW. Grade ≥ 3 AEs occurred in 54/41/57% of QD/MWF/MTuW pts; 17/14/13% discontinued due to AEs and 13/10/0% died on study. MLN1117 (100–900 mg) exhibited a median Tmax of ~4 h and a dose-dependent increase in exposure with moderate-high PK variability (mean %CV on AUC0-24h ~50–70%); wkly exposures in MWF/MTuW pts were ~4 times higher than QD dosing. Mean plasma t1/2 was ~11 h with no appreciable accumulation in plasma. MLN1117 200–900 mg suppressed p4EBP1 and pS6 in skin by up to ~100% and 70–90%, respectively, at ~3 h post-single dose. Per RECIST, there were 3/1/0 PRs (QD/MWF/MTuW) in breast and gastric cancers; 4/7/5 pts had stable disease lasting 105–466 d. Conclusions: In this first-in-human study (n = 76), the safety profile of MLN1117 was acceptable for MWF/MTuW dosing ≤ 900 mg. MWF/MTuW schedules enabled higher doses and weekly exposures vs QD dosing. PD data indicate PI3K pathway inhibition. Objective responses show antitumor activity in advanced solid tumors (n = 4). Clinical trial information: NCT01449370.
Antitumor effect of SCV-07 in murine lung and renal cancer models
Authors: L. Zou, A. Kung, Y. Liu, X. Cui, C. Tuthill
Journal: Journal of Clinical Oncology (2008)

14012 Background: SCV-07 (γ-Glu-Trp) is an immunomodulatory peptide with demonstrated antitumor effects in the murine B16 melanoma model. Herein, the antitumor effects of SCV-07 were evaluated in mice bearing Lewis lung carcinoma (LLC) or renal carcinoma (RenCa) cells. The effect on growth of cultured LLC and RenCa cells was also evaluated to address whether the antitumor effect of SCV-07 is mediated by cytotoxicity. Methods: LLC and RenCa cells were implanted subcutaneously (sc) into the right axillary area of C57BL/6 and Balb/C mice, respectively. SCV-07 was sc administered (at a site different from tumor implantation) once daily at doses of 10 or 20 mg/kg (for LLC) and 5 or 10 mg/kg (for RenCa) for 14 consecutive days. Cisplatin (CDDP, given at 6 mg/kg on days 1, 6, and 12) and cyclophosphamide (CTX, given at 40 mg/kg every other day) were positive controls for LLC and RenCa tumors, respectively. The animals were euthanized on the termination day (day 16 in LLC model, day 17 in RenCa model) and tumors excised and weighed. For the evaluation of cytotoxic effect, LLC or RenCa cells were cultured in 96-well plates with SCV-07 at various concentrations, ranging up to 100 μg/mL, representing the plasma concentrations after effective doses in the mouse models. After 48- (LLC) or 72- (RenCa) hour incubation, inhibitory effects on cell proliferation were determined by the MTT method. Results: In both LLC and RenCa cancer models, SCV-07 treatment led to significant inhibition of tumor growth compared to vehicle control. On the day of study termination, decreases of 16.84% (p<0.05) and 37.45% (p<0.01) in LLC tumor weight were seen after SCV-07 treatment at 10 and 20 mg/kg, respectively, and decreases of 30.02% (p<0.01) and 28.33% (p<0.01) in RenCa tumor weight seen at 5 and 10 mg/kg, respectively. Growth inhibition in the controls were 77.35% (p<0.01) for LLC and 90.12% (p<0.01) for RenCa. In the cultured LLC or RenCa cells, SCV-07 did not inhibit cell proliferation at any tested concentration. Conclusions: Administration of SCV-07 once daily for 14 consecutive days via the sc route is effective against growth of LLC and RenCa tumors. SCV-07 does not induce in vitro cytotoxic effects in cultured LLC and RenCa tumor cells, indicating the antitumor effect of SCV-07 is related to its immunomodulatory actions, rather than cytotoxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration SciClone Pharmaceuticals, Inc. SciClone Pharmaceuticals, Inc SciClone Pharmaceuticals, Inc.
Abstract 14803: KChIP2 Leads to Changes in Cardiac Gene Expression Through Transcriptional Control of miR-34s
Authors: Drew Nassal, Haiyan Liu, Eckhard Ficker, Isabelle Deschenes
Journal: Circulation (2013)

Introduction: Cardiac ion channels and their accessory subunits are critical in maintaining proper cardiac electrical activity. Importantly, the K+ channel interacting protein 2 (KChIP2) is emergin...
In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection
Authors: Xiaonan Zhang, Wei Lu, Ye Zheng, Weixia Wang, Lu Bai, Liang Chen, Yanling Feng, Zhanqing Zhang, Zhenghong Yuan
Journal: Journal of Clinical Investigation (2016)

Persistent hepatitis B virus (HBV) infection is established by the formation of an intranuclear pool of covalently closed circular DNA (cccDNA) in the liver. Very little is known about the intrahepatic distribution of HBV cccDNA in infected patients, particularly at the single-cell level. Here, we established a highly sensitive and specific ISH assay for the detection of HBV RNA, DNA, and cccDNA. The specificity of our cccDNA probe set was confirmed by its strict intranuclear signal and by a series of Southern blot analyses. Use of our in situ assay in conjunction with IHC or immunofluorescence uncovered a surprisingly mosaic distribution of viral antigens and nucleic acids. Most strikingly, a mutually exclusive pattern was found between HBV surface antigen-positive (HBsA-positive) and HBV DNA- and cccDNA-positive cells. A longitudinal observation of patients over a 1-year period of adeforvir therapy confirmed the persistence of a nuclear reservoir of viral DNA, although cytoplasmic DNA was effectively depleted in these individuals. In conclusion, our method for detecting viral nucleic acids, including cccDNA, with single-cell resolution provides a means for monitoring intrahepatic virological events in chronic HBV infection. More important, our observations unravel the complexity of the HBV life cycle in vivo.
A phase IIb actively controlled study with the TGF-beta-2 inhibitor AP 12009 for recurrent or refractory anaplastic astrocytoma
Authors: U. Bogdahn, A. Mahapatra, V. E. Olyushin, C. Mouli, V. E. Parfenov, G. Stockhammer, S. Ludwig, G. Wuerth, H. Heinrichs, K. Schlingensiepen
Journal: Journal of Clinical Oncology (2007)

2025 Background: The TGF-β2 antisense phosphorothioate oligonucleotide inhibitor AP 12009 is a targeted anti-tumor therapy for TGF-β2 overexpressing tumors. In three Phase I/II dose escalation studies complete and long-lasting responses were observed in patients with recurrent or refractory anaplastic astrocytoma. Methods: The Phase IIb actively controlled dose finding study G004 is an open-label, randomized trial in adult patients with recurrent or refractory high-grade glioma (HGG) confirmed by central histopathology. 145 patients were randomized into three groups: Low dose AP 12009 (10 μM), high dose AP 12009 (80 μM), or standard chemotherapy, i.e. TMZ (or PCV if TMZ had already failed). Study objective was to compare the efficacy and safety of the three treatment groups. AP 12009 was applied locoregionally by convection- enhanced delivery (CED) with up to 11 treatment cycles (7-day-on, 7-day-off / per cycle). Results: Here we report on patients with recurrent anaplastic astrocytoma (AA, Grade III; GBM patients see separate abstract). 39 AA patients were treated, 12 pts received AP 12009 10 μM (AP-10), 15 pts 80 μM (AP-80), and 12 pts standard chemotherapy (10 pts TMZ, 2 pts PCV). Preliminary safety data reveal no SAEs related to the study drug in the AP-10 and AP-80 groups vs. one in the control group. Survival rates were higher in both AP 12009 groups compared to the chemotherapy group (see table ). In both AP 12009 groups mOS has not yet been reached. Overall survival at present is 28.6 months for the AP-10 group, 24.2 months for the AP-80 group, and 20.2 months for the control group. Dose finding was achieved, as efficacy and safety results for the AP-10 group were superior to those of the AP-80 group (see table ). Conclusion: AP 12009 revealed a positive benefit-risk profile and demonstrated excellent potential as monotherapy for the treatment of recurrent or refractory AA patients, especially for the AP 12009 10 μM group. [Table: see text] [Table: see text]
Tumors in Amphibians. I. Histology of a Neuroepithelioma in &lt;italic&gt;Siredon mexicanum&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Victor V. Brunst, Augustine L. Roque
Journal: JNCI Journal of the National Cancer Institute (1967)

A spontaneous tumor, transplantable only in some instances, developed in the roof of the mouth in two adult Mexican axolotls (Siredon mexicanum). Histological study showed that the tumor consisted of many lobes or tubes, and the central cavities or lumens often contained coagulated material. The surface of the tumor was covered with typical skin epithelium, containing Leydig cells, but there was no connection between the tumor and the skin. The interstitial connective tissue separating the lobes of the tumor was the usual loose connective tissue, typical of the adult axolotl. Mitosis was very rare in the skin epithelium covering the surface of the tumor and in the connective tissue separating the lobes. Mitotic activity was very great in some portions of the lobes of the tumor, but was limited in other portions of the tumor. Most of the cells of the tumor were bipolar. They were often fusiform, with a large, ovoid nucleus and prominent nucleoli. Intracellular fibrils were typically stained red with chromotrope aniline blue and black with the silver stain, and hence can be considered neurofibrils. The structure of the tumor, with a central lumen and a layer of bipolar cells, was highly reminiscent of the embryonic neuroepithelium. Accordingly, this tumor can be regarded as a neuroepithelioma.
Risk of second lung cancer in patients with previously treated lung cancer: Analysis of the Surveillance, Epidemiology and End Results (SEER) registry
Authors: P. Sivakumaran, S. M. Gadgeel, A. Schwartz, F. Vigneau, K. Islam, A. Wozniak
Journal: Journal of Clinical Oncology (2008)

8048 Background: Second lung cancer (ca) in patients (pts) with prior lung cancer is a recognized, but ill-defined clinical event. To further delineate this phenomenon, we conducted an analysis of SEER data to characterize the risks of developing a 2nd lung ca in these pts. Patients and Methods: Lung ca pts diagnosed in the SEER data from 1973–2001 were included. Standardized incidence ratios (SIRs) were calculated to assess the risks of developing subsequent lung ca in these pts in relation to the general population. Results: 186,610 lung ca pts in the SEER data met eligibility for the study. 61% were males, 24% had localized stage and 88% had initial non-small cell ca (NSCLC). 3479 (2%) of these pts went on to develop a 2nd lung ca. 60% of these pts were males, 41% of the 2nd lung ca were localized stage, and 96% of the 2nd lung ca were NSCLC. The median time to development of a 2nd lung ca was 60 months in males and 67 months in females. Male and female lung ca pts had approximately two-fold and four- fold increased risks of developing a 2nd lung cancer, respectively (SIR: Males - 2.10, Females - 3.80). The risks of 2nd lung ca in male and female pts < 50 years were 4-fold and 9-fold higher, respectively, while for pts ≥ 70 years, these corresponding values were 1.6 and 3.0-fold higher. Among pts who developed 2nd lung ca, histology was the same in the 1st and 2nd cancers in 45% of adenocarcinomas and 48% of squamous cell ca. The risk of 2nd lung ca increased slightly from1973–1982 (SIR- 2.52) to1993–2002 (SIR- 3.03). Localized stage presentation among 2nd lung ca was 38% in 1973–82 and 46% in 1993–2001. Conclusions: Lung ca pts have a significantly higher risk of developing another lung ca when compared to the general population, particularly for pts < 50 years. The median time to development of 2nd lung cancer was approximately 5 years. Only 41% of 2nd lung cancers presented with localized stage. These data have important implications regarding screening principles for 2nd lung ca. These data suggest that follow-up and screening for 2nd lung ca should be maintained over time, in an effort to detect 2nd lung ca at an earlier stage particularly in the younger population. No significant financial relationships to disclose.
Abstract 15607: Prevalence of Atrial Fibrillation (AF) Risk Factors and Lone AF in a General Healthcare Population
Authors: Jeffrey L Anderson, Stacey Knight, Heidi T May, T J Bunch, Donald L Lappe, Joseph B Muhlestein
Journal: Circulation (2012)

Background: Evidence is increasing that genetic factors play a major role in AF predisposition, yet known variants explain only a small percentage of its polygenetic basis. Large AF populations enr...
Effects of Chronic Transfusion Therapy on transcranial Doppler Ultrasonography Velocities in Children with Sickle Cell Anemia at Risk for Primary Stroke: Baseline Findings from the Twitch Trial
Authors: Hamayun Imran, Banu Aygun, Barry R. Davis, Sara L. Pressel, William Herbert Schultz, Sherron M. Jackson, Sharon A. Singh, Sharada A. Sarnaik, Cynthia A. Gauger, Beng Fuh, Kathleen J. Helton, Donna Roberts, Robert J. Adams, Russell E. Ware
Journal: Blood (2014)