tbuckley/cabot-search huggingface dataset:
CD44+ Cells in Head and Neck Squamous Cell Carcinoma Suppress T-Cell–Mediated Immunity by Selective Constitutive and Inducible Expression of PD-L1
Authors: Yunqin Lee, June Ho Shin, Michelle Longmire, Hua Wang, Holbrook E. Kohrt, Howard Y. Chang, John B. Sunwoo
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Human tumors consist of heterogeneous populations of cells with distinct marker expression and functional properties. In squamous cell carcinoma of the head and neck (SCCHN), CD44 is a well-characterized marker of a resilient subpopulation of cells associated with increased tumorigenesis, radioresistance, and chemoresistance. Evidence indicates that these cells have an immunosuppressive phenotype; however, mechanisms have been elusive. Experimental Design: Using primary human SCCHN tumor samples and patient-derived xenografts, we examined the phenotypes of subsets of tumor cells and investigated mechanisms regulating their immunogenicity. Results: CD44+ cells in primary human SCCHN were found to have an epithelial-to-mesenchymal (EMT) phenotype and were less immunogenic than CD44− cells when cultured with autologous CD8+ tumor-infiltrating T cells. Selective expression of the programmed death-ligand 1 (PD-L1) was observed on CD44+ cells compared with CD44− cells and was associated with constitutive phosphorylation of STAT3 on CD44+ cells. Importantly, inhibition of STAT3 decreased expression of PD-L1 on CD44+ cells. IFNγ treatment preferentially induced even further PD-L1 expression on CD44+ cells and was associated with enhanced IFNγ receptor expression and phosphorylation of STAT1. Finally, the decreased immunogenicity of CD44+ cells was partially reversed by antibody blockade of the programmed death 1 (PD-1) receptor, indicating that the differences in PD-L1 expression between CD44+ and CD44− cells are biologically and clinically relevant. Conclusions: Our findings provide a mechanism by which long-lived CD44+ tumor-initiating cells can selectively evade host immune responses and provide rationale for targeting the PD-1 pathway in the adjuvant therapy setting of SCCHN. Clin Cancer Res; 22(14); 3571–81. ©2016 AACR.
Phase 2 Study of Second-Line Dovitinib (Tki258) in Patients with Fibroblast Growth Factor Receptor 2 (Fgfr2)-Mutated or -Nonmutated Advanced and/or Metastatic Endometrial Cancer
Authors: G.E. Konecny, N. Finkler, A.A. Garcia, D. Lorusso, P. Lee, R. Rocconi, P.C. Fong, M. Squires, K. Mishra, A. Upalawanna, Y. Wang, R. Kristeleit
Journal: Annals of Oncology (2014)
Abstract 13630: Regional Ros Production Causes Ca2+ Waves in the Myocardium with Nonuniform Contraction
Authors: Yuhto Taguchi, Masahito Miura, Yuka Kato, Tetsuya Hando, Mai Sasaki, Chiyohiko Shindoh
Journal: Circulation (2014)

Introduction: In diseased hearts, Ca2+ is dissociated from the myofilaments during the relaxation phase due to the paradoxical shortening of the impaired muscle by relaxation of the more viable neighboring muscle. This dissociated Ca2+ initiates Ca2+ waves from the border zone (BZ) between the impaired muscle and the viable muscle. It is still unclear, however, why Ca2+ waves can be initiated from the BZ but not from the impaired muscle. We examined whether reactive oxygen species (ROS) production plays a role in their initiation using the myocardium with nonuniform contraction. Methods: Trabeculae were dissected from rat hearts. Force was measured with a strain gauge, and intracellular Ca2+ (Cai) with fura-2 and a CCD camera. To assess ROS production, the fluorescence of 2’,7’-dichlorofluorescein (DCF) was measured with a CCD camera. Nonuniform contraction was produced by a jet of 2,3-butanedione monoxime (20 mM) solution. Ca2+ waves were induced by stimulation at 400 ms intervals for 7.5 s (24oC, Cao 2....
Age-related effects on the pharmacodynamic (PD) relationship between STEALTH liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors
Authors: L. J. Maruca, R. K. Ramanathan, S. Strychor, B. A. Zamboni, S. Ramalingam, R. P. Edwards, J. K. Kim, Y. J. Bang, H. P. Lee, W. C. Zamboni
Journal: Journal of Clinical Oncology (2007)

2576 Background: STEALTH liposomal CKD-602 (S-CKD602), a camptothecin analogue, is eliminated by the reticuloendothelial system (RES), which consists of cells including monocytes. CKD-602 released from S-CKD602 is eliminated by the kidney. Therefore, we evaluated the PD relationship between monocyte and absolute neutrophil counts (ANC; as a control) in blood and S-CKD602 and non-liposomal CKD-602 (NL-CKD602) in patients (pts) with refractory solid tumors. We also evaluated the effect of age on these relationships. Methods: In a phase I study, S-CKD602 was administered IV x 1 q 3 wk at 0.1 to 2.5 mg/m 2 . In phase I and II studies, NL-CKD602 was administered IV qdx5d q 3 wk at 0.5 to 0.9 mg/m 2 /d and 0.5 mg/m 2 /d, respectively. The % decreases in ANC and monocytes at nadir were calculated. For S-CKD602, pharmacokinetic studies of encapsulated (E), released (R), and sum total (ST=E+R) CKD-602 in plasma and ST in urine were performed and measured by LC-MS/MS. Area under the plasma concentration versus time curve (AUC) was calculated. Results: For S-CKD602 in all pts (n = 27), the % decrease in ANC and monocytes were 42 ± 30 % and 58 ± 34 %, respectively (P = 0.003). For S-CKD602 in pts &lt; 60 years old (yo) (n = 12), the % decrease in ANC and monocytes were 43 ± 31% and 58 ± 26 %, respectively (P = 0.001). For S-CKD602 in pts = 60 yo (n = 15), the % decrease in ANC and monocytes were 41 ± 31% and 45 ± 36 %, respectively (P = 0.50). For NL-CKD602 (n = 42), % decrease in ANC and monocytes were similar (P &gt; 0.05). For S-CKD602, the relationship between % decrease in monocytes and released CKD-602 AUC in plasma in pts &lt; 60 yo (R 2 = 0.54) and = 60 yo (R 2 = 0.49) was similar. For S-CKD602, the relationship between the % decrease in monocytes and the amount of CKD-602 recovered in the urine was stronger in pts &lt; 60 yo (R 2 = 0.82) compared with = 60 yo (R 2 = 0.30). Conclusions: Monocytes are more sensitive to S-CKD602 compared with neutrophils and the increased sensitivity is related to the liposomal formulation and not CKD-602. These results suggest that monocytes engulf S-CKD602 which causes the release of CKD-602 from the liposome and toxicity to the monocytes, and that the effects are more prominent in pts &lt; 60 yo. [Table: see text]
Phase I clinical and pharmacokinetic study of thiotepa administered intraperitoneally in patients with advanced malignancies.
Authors: S Wadler, M J Egorin, E G Zuhowski, L Tortorello, K Salva, C D Runowicz, P H Wiernik
Journal: Journal of Clinical Oncology (1989)

An important subset of malignancies arising in the ovary or digestive organs remains confined to the peritoneal cavity throughout its natural course. These tumors constitute appropriate targets for loco-regional therapy. With this rationale a clinical phase I and pharmacokinetic study of intraperitoneally administered N, N', N'' triethylenethiophosphoramide (thiotepa), an alkylating agent with activity against ovarian carcinoma, was initiated with the objectives of determining the systemic and local toxicities, maximum-tolerated dose, and pharmacokinetic advantage associated with using the drug in this manner. A total of 13 patients received 15 courses of intraperitoneal thiotepa at doses ranging from 30 mg/m2 to 60 mg/m2. The only important systemic toxicity observed was myelosuppression. At 50 mg/m2 two patients developed Eastern Cooperative Oncology Group (ECOG) grade III myelosuppression. At 60 mg/m2, the maximum-tolerated dose, the mean nadir WBC and platelet counts were 2.7 X 10(3)/microliter and 110 X 10(3)/microliter, respectively. There were no instances of vomiting, stomatitis, or alopecia. Pharmacokinetic studies performed in nine patients revealed that thiotepa was rapidly lost from the peritoneal cavity in a biexponential fashion with a mean t1/2 alpha of 0.26 +/- 0.08 hour and a mean t1/2 beta of 2.13 +/- 0.52 hour. Concomitant with the rapid loss of drug from the peritoneal cavity was the rapid rise in drug levels in the plasma, with peak plasma values approaching those associated with intravenous administration. Peritoneal exposure to thiotepa expressed as the area under the curve (AUC)peritoneal fluid was 7 to 34 micrograms/mL X hour. Systemic exposure expressed as the AUCplasma ranged between 0.95 and 7.71 micrograms/mL X hour. The observed pharmacokinetic advantage of intraperitoneal administration calculated as AUCperitoneal fluid/AUCplasma was 4.3 +/- 0.6. This relatively small advantage, combined with our observation of rapid appearance of the active metabolite, tepa, into the plasma argue against an important role for intraperitoneal administration of thiotepa.
Lamella-Particle Complexes in Nuclei of Owl Monkey Kidney Cells Infected With Herpesvirus saimiri
Authors: William G. Banfield, Cecil W. Lee, Tommie Sue Tralka, Alan S. Rabson
Journal: JNCI Journal of the National Cancer Institute (1977)

A complex consisting of ribosome-like particles and a striated lamella occurring in stacked, tubular, and twisted ribbon-like configurations was observed in the nuclei of confluent monolayer cultures of primary owl monkey kidney cells infected with Herpesvirus saimiri. They were similar to the cytoplasmic cylindroid structures seen in some human leukemias and in the lymphoma of the northern pike.
Response to Letter Regarding Article, “Effect of Tumor Necrosis Factor Inhibitor Treatment on Proximal Right Coronary Chronic Total Occlusion in a Patient With Rheumatoid Arthritis”
Authors: Michael Behnes, Ibrahim Akin, Martin Borggrefe, Dominik Traunwieser, Hans Neuser, Kambis Mashayekhi
Journal: Circulation (2015)
Do women younger than 40 treated in the hormone-therapy era benefit from a radiotherapy boost as a part of adjuvant breast radiotherapy?
Authors: Scott Tyldesley, Elisa K. Chan, Caroline Speers, Alan Nichol
Journal: Journal of Clinical Oncology (2014)

72 Background: The EORTC 22881 trial showed a 10% reduction in local relapse with a radiotherapy boost (RTB) after breast conserving therapy (BCT) among women ≤40 years old. However no premenopausal patients received hormone therapy (HT) in this study. A policy change in December 1998 recommended the use of HT after chemotherapy for premenopausal ER positive women. A second policy change in December 2001 recommended an RTB after BCT for women ≤40 years old. The purpose of our study was to describe: 1)how the use of HT and RTB after BCT changed after practice guidelines were implemented in a population-based cancer care program; and 2) how local relapse rates (LRR) changed after these policy changes. Methods: A provincial database was used to analyse all women ≤ 40 years old referred for consideration of radiotherapy with margin negative stage 1 and 2 (≤3 nodes positive) breast cancer, treated with lumpectomy and whole breast radiotherapy. Cases were grouped into three eras according to policy transition with 3 month gaps: 1) Jan 1996-Sep 1998, 2) Jan 1999-Sep 2001, 3) Jan 2002 to Sep 2004. Changes in the use of HT and RTB over these eras were assessed. Eight year LR-free survival was calculated using the Kaplan-Meier method and the three eras compared using log rank tests. Multivariable analysis (MVA) was performed including era, size of tumour, nodal status (0 vs 1-3), grade, lymphovascular space invasion (LVI), and use of chemotherapy. Results: There were 130 eligible patients from Era 1, 145 patients from Era 2, and 140 patients from Era 3. ER status did not differ across eras. HT was used for ER positive patients in 13% of Era 1, 68% of Era 2, and 83% of Era 3 cases (p&lt;0.001). RTB was used in 40% of Era 1, 28% of Era 2, and 77% of Era 3 patients (p&lt;0.001). LRR at 8 years were 87.3% Era 1, 94.8 % Era 2, and 94.5% Era 3 (p=0.03). Era (used as surrogate for transitions in the use of HT and RTB) remained significant on MVA (0=0.008). Conclusions: Patterns of use of HT and RTB changed after policy changes. The benefit of adding a boost in women ≤40 years old shown by the EORTC was not observed after the introduction of routine HT at a population level.
Serum prostate-specific antigen: expanding its role as a measure of treatment response in patients with prostate cancer.
Authors: G L Andriole
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.4.596 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7683042 Serum prostate-specific antigen: expanding its role as a measure of treatment response in patients with prostate cancer. G L AndriolexG L AndrioleSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.4.596 PDF "Serum prostate-specific antigen: expanding its role as a measure of treatment response in patients with prostate cancer.." Journal of Clinical Oncology, 11(4), pp. 596–597© 1993 by American Society of Clinical Oncology
Isolation of Plasma Membrane Antigens from Epstein-Barr Virus-Infected Lymphoid Cells
Authors: Charles W. Boone, Paul Gerber, Phyllis B. Brandchaft
Journal: JNCI Journal of the National Cancer Institute (1973)

The plasma membrane fraction of Epstein-Barr virus (EBV)-infected lymphoid cells was isolated on sucrose density gradients in an attempt to also isolate EBV-coded membrane antigen (MA). The surface HL-A and xenoantigens of these cells were readily isolated in this way. The location of antigens on the gradients was monitored by bound radioiodine-labeled proteins from MA-reactive sera and normal sera introduced by incubation of intact cells with labeled proteins before fractionation (paired-label technique). Though the cells used were 40% positive for MA by membrane immunofluorescence before fractionation, No detectable MA remained associated with the plasma membrane after fractionation. However, a peak of antibody-bound material appeared in the denser region of the gradients which contained EBV by electron microscopy. No detectable soluble MA-antibody complexes were released during the isolation procedure. In contrast to the stronger bonds which hold HL-A and xenoantigens to the plasma membrane, the MA-membrane bond appears to be weak enough to be broken during hypotonic treatment and mechanical rupture of the cells. We conclude that the majority of cells in an EBV carrier culture that are positive for MA by immunofluorescence may be carrying EBV and MA-positive membranous debris adsorbed to their surfaces derived from the perinuclear and endoplasmic membranes of degenerating infected cells.
Group I introns within the nuclear-encoded small-subunit rRNA gene of three green algae.
Authors: L W Wilcox, L A Lewis, P A Fuerst, G L Floyd
Journal: Molecular Biology and Evolution (1992)

Four group I introns from the nuclear-encoded (18S) rRNA genes of three chlorophycean green algae are described; two are in Dunaliella parva, and one each is in D. salina and Characium saccatum. The introns within the gene in the latter two organisms are located at the sites equivalent to the 5' and 3' introns of D. parva, respectively. All four introns lack open reading frames and are relatively small, 381-447 bp. Both primary- and secondary-structural features place these introns within subgroup IC1 described by Michel and Westhof. Phylogenetic relationships of the three intron-containing taxa and their relatives, as inferred from comparisons of 18S rDNA sequences, suggest that inheritance of the introns along with the gene can account for their present distribution. The discovery of these four introns, in addition to two others known to exist in other chlorophycean green algae, suggests that group I introns within the 18S rRNA gene may be relatively common in the green algae.
A Case of Relapsed Lymphoplasmacytic Lymphoma with Marked Response of Bendamustine Hydrochloride
Authors: Takenori Takahata, Satoshi Tanaka, Naoyuki Hanada, Kensuke Saitoh, Hiroto Hiraga, Hirotake Sakuraba, Shinsaku Fukuda, Atsushi Sato
Journal: Annals of Oncology (2014)
Augmentation of Antitumor Antisera Activity by Lyophilization
Authors: Peter C. Ungaro, Walter P. Drake, Michael R. Mardiney
Journal: JNCI Journal of the National Cancer Institute (1973)

Antisera were concentrated by fractionation and lyophilization. The resultant antisera had from 5–7 times the cytotoxic activity that they had beFore the procedure. The sera obtained by this method were more effective in tumorserotherapy than were unconcentrated sera.
Epidemiology of Minimal Breast Cancer Among Women Screened in New York City&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Neil Dubin, Robert V. P. Hutter, Philip Strax, Eugene P. Fazzini, Roger A. Schinella, Eduardo S. Batang, Bernard S. Pasternack
 7
Journal: JNCI Journal of the National Cancer Institute (1984)

A case-control study based on a screened population in New York City examined epidemiologic risk factor differences between minimal breast cancer (in situ and small invasive carcinomas) and all other breast carcinomas, referred to as clinical breast cancer. Histopathologic re-review of the original slides identified 113 minimal and 792 clinical breast cancers among 1,290 eligible cases; 2,173 randomly selected screenees served as controls. Among those who developed cancer, black women were twice as likely to develop minimal, as compared to clinical, breast cancer. Women who were less than 20 years of age at first live birth had more than double the probability of being diagnosed with minimal breast cancer, whereas women with first live birth at age 30 years or greater and nulliparous women were at 1.5 times the risk of clinical breast cancer. The relative proportion of minimal breast cancer increased with increasing number of children breast fed, being twofold among women who nursed 2 children or more. Unlike clinical breast cancer, minimal breast cancer was not associated with either family history of breast cancer or obesity. Meaningful histologic differences were not apparent between the case subgroups. Except possibly for obesity, these results could not be explained by any plausible diagnostic bias.
Leptomeningeal Enhancement in a Patient With Progressive Cranial Neuropathies and Lumbosacral Radiculopathies
Authors: Treasach C. Vargas, Richard L. Thomas, Jay C. Erickson
Journal: JAMA Neurology (2016)

A 69-year-old white man presented to the emergency department reporting 2 months of progressive bilateral lower extremity weakness, left facial weakness, and diplopia in the setting of a 20.4-kg weight loss over the previous 6 months and new onset urinary incontinence. What is your diagnosis?
JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma
Authors: M-L Nairismägi, J Tan, J Q Lim, S Nagarajan, C C Y Ng, V Rajasegaran, D Huang, W K Lim, Y Laurensia, G C Wijaya, Z M Li, I Cutcutache, W L Pang, S Thangaraju, J Ha, L P Khoo, S T Chin, S Dey, G Poore, L H C Tan, H K M Koh, K Sabai, H-L Rao, K L Chuah, Y-H Ho, S-B Ng, S-S Chuang, F Zhang, Y-H Liu, T Pongpruttipan, Y H Ko, P-L Cheah, N Karim, W-J Chng, T Tang, M Tao, K Tay, M Farid, R Quek, S G Rozen, P Tan, B T Teh, S T Lim, S-Y Tan, C K Ong
Journal: Leukemia (2016)

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
Lenalidomide and rituximab for the initial treatment of chronic lymphocytic leukemia: Report of an ongoing study.
Authors: D. F. James, J. R. Brown, L. Werner, W. G. Wierda, K. R. Rai, J. Gould, J. E. Castro, L. Rassenti, D. S. Neuberg, T. J. Kipps
Journal: Journal of Clinical Oncology (2010)

6583 Background: Lenalidomide (L) is an immunomodulatory agent and rituximab (R) a mAb with therapeutic activity in CLL. A phase II study was designed to evaluate this immunotherapy combination in treatment-naïve CLL pts with an indication for therapy. Methods: Pts were eligible if they had normal kidney function and no recent thromboembolic events. Pts started L at 2.5 mg/day (D) and could escalate to 5 mg/D on D8 to a maximum of 10 mg/D if tolerated. Pts received L 21/35 D for cycle (C) 1, then for 21/28 D for C2-7. R 50 mg/m2 D29, 325 mg/m2 D31, 375 mg/m2 D33, C1, then 375 mg/m2 weekly × 4 for C2 and on D1 for C3-7. Pts received allopurinol for tumor lysis prophylaxis. Results: 37 pts have been enrolled, 34 have demographic data and 30 evaluable for toxicity. Median age was 62 yrs (56 arm A, 73 arm B). 17/34 pts were Rai stage III-IV (40% arm A, 63% arm B). 16/31 pts had unmutated IgVH. FISH analysis revealed deletion of 17p (3 pts) and 11q (3 pts). The most common grade III/IV adverse events (AE) were neutropenia (18 pts), anemia (5 pts), and thrombocytopenia (4 pts). There were no cases of neutropenic fever, sepsis, or bleeding. Nonhematologic grade III/IV AEs included infection (3 pts arm B), rash (2 pts), and pulmonary embolus (PE) (1 pt per arm). The protocol was amended to include aspirin prophylaxis. Most frequent AEs (all grades) were the tumor flare reaction (TFR) (21/30), fatigue (19/30), and transient elevation of liver transaminases (25/30). TFR occurred in 15/17 pts (arm A) and 6/12 (arm B). Only a fraction of pts experienced TFR following the institution of R. Biochemical tumor lysis was observed in 2 pts without clinical tumor lysis. There have been no deaths. Median dose was 10 mg (arm A) and 5 mg (arm B) for pts that received > 3 cycles. 7 pts have been removed from study, 1 ineligible, 1 intolerance to R, 1 due to PCP, 1 with PE, 1 rash, and 1 thrombocytopenia. No pts have been removed for progressive disease. At interim analysis the criteria for continuing accrual to a total of 40 pts in each stratum were met with at least 2 clinical complete responses in each arm. Conclusions: Early results of the ongoing study suggest that immunotherapy with L and R is tolerable. TFR, a frequent AE did not usually occur following C1 possibly related to the use of R. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene Celgene
원저 : 연속적으로 시행한 공장 근로자 건강검진에서 무증상 간기능검사 이상자의 임상적 특성
Authors: 김강모 ( Kang Mo Kim ), 김윤준 ( Yoon Jun Kim ), 이광혁 ( Kwang Hyuck Lee ), 백도명 ( Do Myung Paek )
Journal: Clinical and Molecular Hepatology (2005)

목적: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltranspeptidase (γ-GT)와 같은 간기능검사는 간질환에 대한 선별 검사로 자주 사용되고 있으나 낮은 양성 예측도로 인해 위양성자가 많은 단점이 있다. 이번 연구에서는 건강검진을 위해 연속적으로 간기능검사를 시행한 코호트를 대상으로 간기능검사 이상자를 분류하고 연속적으로 간기능 이상으로 나오는 군의 위