tbuckley/cabot-search huggingface dataset:
Abstract 2016: Evaluation of prostate cancer biomarkers and therapeutic targets in FFPE specimens using the NanoString platform
Authors: Jocelyn Lee, Wusheng Yan, Denise Young, Yingjie Song, Yongmei Chen, Shilpa Katta, Ahmed Mohamed, Lakshmi Ravindranath, Alagarsamy Srinivasan, Jennifer Cullen, Jacob Kagan, Sudhir Srivastava, Albert Dobi, Inger Rosner, David G. McLeod, Isabell A. Sesterhenn, Shiv Srivastava, Gyorgy Petrovics
Journal: Cancer Research (2015)

Abstract Introduction: Identification of prognostic indicators of disease progression is one of the highest priorities in prostate cancer (CaP) research. The majority of CaP tissue specimens available for biomarker discovery and validation are formalin fixed paraffin embedded (FFPE) specimens. The RNA quality of these tissues for traditional gene expression analysis approaches is not adequate, especially of cases with long term- follow up necessary for prognostic marker studies. We systematically evaluated and optimized the NanoString platform for CaP gene expression analysis in FFPE whole mounted prostate specimens with up to 15 years follow up. Methods: NanoString readouts were compared between a series of input total RNA prepared through different tissue dissection methods. We then performed NanoString analysis of 151-CaP probe set on 63 archived CaP samples to evaluate this modified protocol. ERG gene expression was validated by immunohistochemistry (IHC) assay using CPDR ERG-MAb (9FY). Results: We have performed NanoString analysis of CPDR designed 151- CaP gene panel on whole-mounted prostate tissue specimens using our optimized protocol. The prostate epithelial cell markers KLK3, MSMB and PAP had the highest signals in all samples reflecting the prostate epithelial origin of the specimens. Established CaP specific genes, such as AMACR, PCA3 and PSGR were most highly over-expressed in tumors compared to matched benign prostate epithelium. ERG positive tumors had strong expression of both TMPRSS2-ERG fusion probes and probes for several ERG splice forms (ERG 1,2,3 and 8), with no signals in the matched benign samples. The ERG gene expression status was consistent with blinded ERG IHC results. Conclusions: The feasibility of NanoString profiling in archived whole mounted FFPE prostate specimens was demonstrated. This approach is well suited for a medium throughput evaluation and validation of prognostic biomarker and therapeutic target candidates in CaP. Citation Format: Jocelyn Lee, Wusheng Yan, Denise Young, Yingjie Song, Yongmei Chen, Shilpa Katta, Ahmed Mohamed, Lakshmi Ravindranath, Alagarsamy Srinivasan, Jennifer Cullen, Jacob Kagan, Sudhir Srivastava, Albert Dobi, Inger Rosner, David G. McLeod, Isabell A. Sesterhenn, Shiv Srivastava, Gyorgy Petrovics. Evaluation of prostate cancer biomarkers and therapeutic targets in FFPE specimens using the NanoString platform. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2016. doi:10.1158/1538-7445.AM2015-2016
Serum levels and pharmacokinetic of rituximab in Bi-weekly R-CHOP in elderly patients with DLBCL treated in the RICOVER-60 trial:
Authors: M. Reiser, M. Wenger, C. Nickenig, N. Peter, B. Metzner, M. Pfreundschuh
Journal: Journal of Clinical Oncology (2006)

7537 Background: The combination of Rituximab (R) and CHOP is considered the standard of treatment for DLBCL in elderly patients (pts) but there is hardly any data on the pharmacokinetic of Rituximab in aggressive lymphoma pts. The RICOVER-60 trial using Rituximab + bi-weekly CHOP-14 resulted in improved TTF in 828 elderly DLBCL pts (Blood 106:9a, 2005). Objective: To study serum levels and pharmacokinetic properties of Rituximab when combined with CHOP-14 in elderly DLBCL pts. Methods: Blood samples of 20 pts were taken before and after Rituximab infusion at each chemotherapy cycle. Additional samples were taken after the end of treatment and at the following time points: after 1 week, 1 month, 2 months, 3 months, 6 months and 9 months, respectively. Peak serum samples were taken within a maximum of 30 min, all samples were centrifuged at 1000 g for 10 min (room temperature) and stored at −20 degrees C. Batch samples were shipped to Xendo Laboratories, Groningen, The Netherlands, and analysed. Results: Samples from 20 pts were evaluable for this analysis with 16/20 pts having completed all 8 cycles of treatment, yet. The median (range) of serum Rituximab levels (μg/ml) before each cycle were: #1 0 (0–0); #2 39 (13–62); #3 74 (47–109); #4 95 (40–136); #5 111 (55–157); #6 114 (12–518); #7 125 (72–207);#8 116 (75–304). After therapy median (range) of serum Rituximab levels were: 163 (67–248) at 1 week; 101 (44–163) at 1 month; 55 (1–123) at 2 months; 34 (1–577) at 3 months; 5 (0–103) at 6 months; 1 (0–128) at 9 months. At 9 months samples from 7 pts were evaluable with detectable serum Rituximab levels in 4/7 pts. Conclusion: In the dose dense regimen R+CHOP-14 Rituximab levels increased after each subsequent cycle for the first 4 cycles. During cycle 5- 8 the serum Rituximab levels reached a plateau and decreased constantly after the end of treatment with detectable levels even after 9 months. Based on this data the German High Grade NHL Study Group (DSHNHL) further investigates a densification of Rituximab in the first cycles in order to improve treatment outcome. A final analysis of all 20 pts and a pharmacokinetic model of Rituximab distribution and elimination phase will be presented at the meeting. [Table: see text]
알코올간질환 : 알코올간염의 임상상과 치료
Authors: 이병석
Journal: Clinical and Molecular Hepatology (2008)

Alcoholic liver disease includes fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Alcoholic hepatitis is an acute and severe form of alcoholic liver disease. Its mortality has been reported high rate. Abstinence and life style modification is very impotant for patients with alcoholic liver disease. There are many drugs for treatment of alcoholic liver disease, especially alcoholic hepatitis. Among those, corticosteroid therapy appears to be beneficial to severe alcoholic hepatitis (DF>32). The benefits of other therapeutic drugs remain controversial. We review the clinical features and treatment modalities of alcoholic liver disease.
Microsatellite evolution in congeneric mammals: domestic and bighorn sheep.
Authors: S H Forbes, J T Hogg, F C Buchanan, A M Crawford, F W Allendorf
Journal: Molecular Biology and Evolution (1995)

We compared genotypes at eight (AC)n microsatellite loci in domestic sheep (Ovis aries) and wild Rocky Mountain bighorn sheep (O. canadensis). The domestic sheep had greater genetic variation, higher allele-size variances, and larger allele sizes than the wild sheep. Accumulating evidence from higher taxonomic comparisons shows that these parameters are biased if microsatellite loci are selected in one taxon and used in another. Our results demonstrate similar biases between congeneric species. We compared standard measures of genetic variation, differentiation, and distance within and between species (H, D, FST) to newer measures based on allele-size variance (SW, SB, RST). The size-based distances better detected species-level divergence, but standard measures better distinguished allopatric populations. Empirical calibration of these measures at the subspecies level is needed to establish their useful ranges.
Joint space narrowing is poorly correlated with symptoms worsening in knee-osteoarthritis: results from the prospective follow-up of 106, placebo-treated patients for three years
Authors: Jean-Yves Reginster, Yves Henrotin, Olivier Bruyère, C. Gonzalez, Giampaolo Giacovelli, Lucio C Rovati
Journal: Annals of the Rheumatic Diseases (2002)
Recurrent Mutations of Chromatin-Remodeling Genes and Kinase Receptors in Pheochromocytomas and Paragangliomas
Authors: Rodrigo A. Toledo, Yuejuan Qin, Zi-Ming Cheng, Qing Gao, Shintaro Iwata, Gustavo M. Silva, Manju L. Prasad, I. Tolgay Ocal, Sarika Rao, Neil Aronin, Marta Barontini, Jan Bruder, Robert L. Reddick, Yidong Chen, Ricardo C.T. Aguiar, Patricia L.M. Dahia
Journal: Clinical Cancer Research (2015)

Pheochromocytomas and paragangliomas (PPGL) are genetically heterogeneous tumors of neural crest origin, but the molecular basis of most PPGLs is unknown.We performed exome or transcriptome sequencing of 43 samples from 41 patients. A validation set of 136 PPGLs was used for amplicon-specific resequencing. In addition, a subset of these tumors was subjected to microarray-based transcription, protein expression, and histone methylation analysis by Western blotting or immunohistochemistry. In vitro analysis of mutants was performed in cell lines.We detected mutations in chromatin-remodeling genes, including histone-methyltransferases, histone-demethylases, and histones in 11 samples from 8 patients (20%). In particular, we characterized a new cancer syndrome involving PPGLs and giant cell tumors of bone (GCT) caused by a postzygotic G34W mutation of the histone 3.3 gene, H3F3A Furthermore, mutations in kinase genes were detected in samples from 15 patients (37%). Among those, a novel germline kinase domain mutation of MERTK detected in a patient with PPGL and medullary thyroid carcinoma was found to activate signaling downstream of this receptor. Recurrent germline and somatic mutations were also detected in MET, including a familial case and sporadic PPGLs. Importantly, in each of these three genes, mutations were also detected in the validation group. In addition, a somatic oncogenic hotspot FGFR1 mutation was found in a sporadic tumor.This study implicates chromatin-remodeling and kinase variants as frequent genetic events in PPGLs, many of which have no other known germline driver mutation. MERTK, MET, and H3F3A emerge as novel PPGL susceptibility genes. Clin Cancer Res; 22(9); 2301-10. ©2015 AACR.
Pharmacokinetics of Irinotecan and SN38 after intra-arterial liver perfusion according to infusion time and circadian patient pattern in metastatic colorectal cancer
Authors: M. Pirovano, A. Nasisi, L. Paraboni, S. Sestini, S. Masseroni, F. Gherardi, G. Martignoni, M. Meregalli, D. Fornasari, F. Scaglione, D. Tabiadon
Journal: Journal of Clinical Oncology (2006)

13557 Chronotherapy studies in pretreated CRC cancer pts showed that 6 hrs chronomodulated CPT11 infusion from 2 to 8 a.m., alone or combined with 5FU+AF±OHP, is less toxic than the standard 90 min. infusion, and CPT11-SN38 convertion efficency is improved with an higer objective response rate. Objective of this study was evaluation of CPT11 pharmacokinetics after hepatic i.a. perfusion according to infusion time and circadian patient pattern. To evaluate patient circadian pattern, serum levels of prolactin and cortisol were detected at 2–6, 4 pm and 2–6, 4 -8 pm respectively. CPT11 and SN38 serum levels were detected, according to two different time schedules, following the HPLC method. Every pt received 240 mg/mq i.a. CPT11 perfusion alternating daily with nightly schedule: from NOV04 to FEB05 5 metastatic CRC patients were treated. All pts concluded all programmed cycles. No cycle was delayed due to toxicity. Haematological, hepatic and g.i. G 3–4 (NCI) toxicity were not observed (only neutropenia G1 in the female subject). Circadian organization seems to be progressively lost according to cycle number. At 3rd cycle, cyrcadian levels of cortisol and prolactin are lost in all pts. Kinetic data suggests for a progressive reduction of liver enzymatic capability; this is probably due to cumulative liver drug toxicity: this phenomenon is clearly evidenced in female subject but is also signicative in the male subjects (see Table). These preliminary data show enormous PK/PD interpatient variability and a significative AUC reduction 2nd cycle vs 1st and 3rd vs 2nd; due to this unespected observation we are not able to evaluate cyrcadian oscillation of enzymatic systems: in order to fully understand these data we decided to perform polimorphism assesment for UGT1A1,Carboxil Esterase isoform2 and ABC transporters genes.This analysis will be performed on paraffin included samples for the first 5 pts and on fresh tissue for the next pt set. [Table: see text] No significant financial relationships to disclose.
Abstract MP047: Early-Onset Coronary Heart Disease Mortality Remains High Among Rural Blacks
Authors: Ambar Kulshreshtha, Abhinav Goyal, William McClellan, Emir Veledar, Viola Vaccarino
Journal: Circulation (2012)

Background: Deaths from early-onset coronary heart disease (CHD) translate into a large number of potential life-years lost with substantial impact on families and society. Although overall CHD mortality has declined in the past few decades, the extent to which such decline applies to early CHD mortality and to specific racial groups and urbanization levels has not been examined. We sought to describe the pattern and magnitude of racial and urban-rural variations in early-onset CHD mortality in the United States. Methods: We used data from the National Center for Health Statistics to examine trends in CHD death rates (ICD-10 codes I20-I25) between 1999 and 2007. Early-onset CHD mortality was defined as death due to CHD in men less than 55 yrs or women less than 65 yrs. Rate changes were calculated in the overall population and by race (blacks vs whites) and urbanization (rural vs. urban). Poisson regression was used to model the data. Results: Between 1999 and 2007, there were approximately 400,000 deaths due to early-onset CHD. There was an overall 25% decline in age-adjusted early-onset CHD mortality rates from 79 per 100,000 to 59 per 100,000 but this decline varied by gender, race, and urbanization. Women had a greater decline (27%) compared with men (19%) and blacks had slightly more decline (27%) compared to whites (25%). Urban areas (30%) had twice the decline compared to rural areas (16%). In this period early CHD deaths was higher in blacks than whites and higher in rural than urban areas (Figure). Blacks in rural areas had the highest early-onset CHD mortality, followed by blacks in large metros, while urban whites had the lowest rate. Black-white differences remained similar in urban and rural areas over this time period. Conclusion: The overall decline in early-onset CHD mortality is encouraging, but there are important differences by race and urbanization. Blacks in rural areas have the highest early-onset CHD mortality rates. Early-onset CHD can be used to identify and target groups with high risk in order to reduce disparities.
Phase I, safety, pharmacokinetic and biomarker study of BAY 57–9352, an oral VEGFR-2 inhibitor, in a continuous schedule in patients with advanced solid tumors
Authors: H. Gelderblom, J. Verweij, N. Steeghs, A. Van Erkel, L. Van Doorn, J. Ouwerkerk, P. Rajagopalan, A. Matthys, D. Voliotis, F. Eskens
Journal: Journal of Clinical Oncology (2006)

3040 Background: BAY 57–9352 is a potent competitive inhibitor of the VEGFR-2 (IC 50 : 6 nM), VEGFR-3 (IC 50 : 4 nM), PDGFR-β and c-KIT tyrosine kinases. BAY 57–9352 showed tumor efficacy in colon, breast, pancreatic and NSCLC models. Methods: Patients with advanced solid tumors received oral BAY 57–9352 on a continuous basis, in escalating doses. One cycle was defined as 21 days of treatment. Extensive PK and PD (dynamic contrast-enhanced MRI [DCE-MRI]) evaluations were performed. Plasma biomarkers (e.g. VEGF)were also evaluated. Results: Forty patients (median 54 yrs) were enrolled at seven dose levels from 20 mg solution once daily to1500 mg twice daily (bid; 150 mg tablets) for a total of 169 cycles (range 1–17). The most frequent drug-related adverse events were nausea, hypertension, headache, vomiting, hoarseness, rash, dry skin and anorexia. One patient treated at 600 mg bid had a dose-limiting toxicity defined by an increase from grade 2 to 3 hypertension, despite the addition of an ACE-inhibitor and Ca-antagonist on day 8 of cycle 2. Another patient at that same dose level and also on day 8 cycle 2, had grade 3 AST/ALT increase, however this was not assessed as dose-limiting. Both patients continued treatment after dose reductions. Treatment was well tolerated, even at the highest dose levels. One patient with a hemangio-endothelioma (600 mg bid) had a clinical response and one desmoid tumor patient (900 mg bid) had a 53% reduction in tumor volume. BAY 57–9352 AUC increased dose proportionally up to 900 mg bid. The target AUC, based on animal models (5 mg × h/L) was reached in all patients at 900 mg bid. Dose levels exceeding 900 mg bid had similar plasma VEGF biomarker levels. Conclusions: BAY 57–9352 was well tolerated in doses up to 1500 mg bid. Based on safety, PK, PD and biomarker assessments, the recommended dose level is 900 mg bid. A 300 mg tablet is being tested for patient convenience. Combination chemotherapy studies have been started. [Table: see text]
Phase I and pharmacologic study of hexamethylene bisacetamide in patients with advanced cancer.
Authors: E K Rowinsky, D S Ettinger, L B Grochow, R B Brundrett, A E Cates, R C Donehower
Journal: Journal of Clinical Oncology (1986)

Hexamethylene bisacetamide (HMBA, NSC 95580) has been demonstrated to be the most effective of the known and studied polar-planar compounds at inducing differentiation in a wide variety of leukemic and nonleukemic cell lines. Although HMBA demonstrated no antineoplastic activity in preclinical testing, it was selected for clinical development on the basis of its potent differentiating capabilities in vitro. In this phase I study, HMBA was administered as a continuous five-day infusion every 3 weeks to patients with advanced cancer. Twenty-three patients received 35 evaluable courses at doses that ranged from 4.8 to 33.6 g/m2/d. Dose-limiting toxicities included renal insufficiency, a hyperchloremic metabolic acidemia/acidosis, and CNS toxicities manifested by agitation and delirium, which progressed to coma in one patient who developed concomitant renal insufficiency. Moderate myelosuppression, mucositis, nausea, and vomiting were also observed. The pharmacokinetics of HMBA best fit a single compartmental model and disposition is primarily by renal elimination. Renal excretion of HMBA and of the primary metabolite, 6-acetoamidohexanoic acid, together account for the disposition of 66% to 93% (mean, 74%) of the infused drug. Based on this trial, the maximum tolerated and recommended phase II doses for HMBA administered on this schedule are 33.6 and 24 g/m2/d, respectively. However, since steady-state HMBA levels at these doses were in the range of 1 to 2 mmol/L, only approaching the lower limit demonstrated for in vitro differentiating effectiveness, and because of evidence suggesting that the exposure period is an important variable in the induction of differentiation, additional studies examining longer periods of infusion are warranted.
Virus-Specific Nucleic Acids in Simian Virus 40-Transformed Hamster Cell Clones Varying in Oncogenic Potential
Authors: S. E. Siegel, A. S. Levine
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Virus-Specific Nucleic Acids in Simian Virus 40-Transformed Hamster Cell Clones Varying in Oncogenic Potential Get access S. E. Siegel, S. E. Siegel Search for other works by this author on: Oxford Academic PubMed Google Scholar A. S. Levine A. S. Levine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 49, Issue 6, December 1972, Pages 1667–1673, https://doi.org/10.1093/jnci/49.6.1667 Published: 01 December 1972 Article history Received: 12 June 1972 Accepted: 22 August 1972 Published: 01 December 1972
Ultrastructure of Wilms' Tumor. I. Epithelial Cell&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ito, Jishu, Johnson, Warren W.
Journal: JNCI Journal of the National Cancer Institute (1969)

Journal Article Ultrastructure of Wilms' Tumor. I. Epithelial Cell Get access Jishu Ito, Jishu Ito St. Jude Children's Research Hospital and University of Tennessee Medical Units, Memphis, Tennessee 38101 Search for other works by this author on: Oxford Academic PubMed Google Scholar Warren W. Johnson Warren W. Johnson St. Jude Children's Research Hospital and University of Tennessee Medical Units, Memphis, Tennessee 38101 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 42, Issue 1, January 1969, Pages 77–99, https://doi.org/10.1093/jnci/42.1.77 Published: 01 January 1969 Article history Received: 19 July 1968 Accepted: 24 September 1968 Published: 01 January 1969
Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis
Authors: Jaishri O. Blakeley, Scott R. Plotkin
Journal: Neuro-Oncology (2016)

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded by NF1) and merlin (encoded by NF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1 and LZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations in NF1 (ie, glioblastoma, breast cancer, melanoma), NF2 (ie, meningioma, mesothelioma) and SMARCB1 (ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations.
Combined evaluation of Rad51 and ERCC1 expressions for sensitivity to platinum agents in non-small cell lung cancer (NSCLC)
Authors: I. Yoshino, T. Takenaka, H. Koso, T. Ohba, T. Yohena, A. Osoegawa, F. Shoji, Y. Maehara
Journal: Journal of Clinical Oncology (2007)

18085 Background: DNA repair enzyme expression in tumor cells possibly affects sensitivity to anti-cancer agents. The aim of this study was to determine the relationship between expression status of DNA repair proteins and chemosensitivity in patients with NSCLC. Rad51 and ERCC1 play important roles in repair of double and single strand breaks of DNA, respectively, and may protect cells from cytotoxic effect of platinum agents. Methods: NSCLC tissues prepared from the surgical specimens of 41 patients were subjected to an immunohistochemical analysis for Rad51 and ERCC1 proteins and to a chemosensitivity test using the MTT assay. The relationships between the expression status of the DNA repair enzymes and ex vivo chemosensitivity to various agents were evaluated. Results: A positive expression for Rad51 and ERCC1 was observed in 17 cases (41%) and 20 cases (49%), respectively. The positivity of Rad51 was closely related to a certain histologic type of squamous cell carcinoma and poor differentiation, and the positivity of ERCC1 tended to be related to squamous cell carcinoma. In chemosensitivity tests, sensitivities to CDDP and CBDCA were significantly lower when both two enzymes were positive (p = 0.012 and 0.04 in CDDP, 0.014 and 0.03 in CBDCA), but not when either or neither of them was positive. Both Rad51 and ERCC1 expressions showed no significant relationship with sensitivities to paclitaxel, etoposide, vinorelbine, gemcitabine, 5-FU, or irinotecan. Conclusions: Combined expression of Rad51 and ERCC1 is associated with resistance to platinum agents in the ex vivo study of clinical NSCLC, and evaluation of expression status of both DNA repair enzymes would be a predictor for clinical response to platinum-based chemotherapies. No significant financial relationships to disclose.