tbuckley/cabot-search huggingface dataset:
Systemic PEGylated TRAIL treatment ameliorates liver cirrhosis in rats by eliminating activated hepatic stellate cells
Authors: Yumin Oh, Ogyi Park, Magdalena Swierczewska, James P. Hamilton, Jong‐Sung Park, Tae Hyung Kim, Sung‐Mook Lim, Hana Eom, Dong Gyu Jo, Choong‐Eun Lee, Raouf Kechrid, Panagiotis Mastorakos, Clark Zhang, Sei Kwang Hahn, Ok‐Cheol Jeon, Youngro Byun, Kwangmeyung Kim, Justin Hanes, Kang Choon Lee, Martin G. Pomper, Bin Gao, Seulki Lee
Journal: Hepatology (2015)

Liver fibrosis is a common outcome of chronic liver disease that leads to liver cirrhosis and hepatocellular carcinoma. No US Food and Drug Administration-approved targeted antifibrotic therapy exists. Activated hepatic stellate cells (aHSCs) are the major cell types responsible for liver fibrosis; therefore, eradication of aHSCs, while preserving quiescent HSCs and other normal cells, is a logical strategy to stop and/or reverse liver fibrogenesis/fibrosis. However, there are no effective approaches to specifically deplete aHSCs during fibrosis without systemic toxicity. aHSCs are associated with elevated expression of death receptors and become sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. Treatment with recombinant TRAIL could be a potential strategy to ameliorate liver fibrosis; however, the therapeutic application of recombinant TRAIL is halted due to its very short half-life. To overcome this problem, we previously generated PEGylated TRAIL (TRAILPEG ) that has a much longer half-life in rodents than native-type TRAIL. In this study, we demonstrate that intravenous TRAILPEG has a markedly extended half-life over native-type TRAIL in nonhuman primates and has no toxicity in primary human hepatocytes. Intravenous injection of TRAILPEG directly induces apoptosis of aHSCs in vivo and ameliorates carbon tetrachloride-induced fibrosis/cirrhosis in rats by simultaneously down-regulating multiple key fibrotic markers that are associated with aHSCs.TRAIL-based therapies could serve as new therapeutics for liver fibrosis/cirrhosis and possibly other fibrotic diseases. (Hepatology 2016;64:209-223).
Vaccination of patients with advanced non-small cell lung cancer with an optimized cryptic hTERT peptide (Vx-001)
Authors: K. Kosmatopoulos, E. Bolonaki, A. Kotsakis, E. Papadimitraki, D. Agouraki, G. Kosnoslakis, A. Vagia, C. Christophylakis, V. Georgoulias, D. Mavroudis
Journal: Journal of Clinical Oncology (2007)

7642 Background: To evaluate the immunological and clinical efficacy of the optimized peptide TERT 572Y (Vx-001) presented by HLA-A*0201 in patients with advanced non-small cell lung cancer (NSCLC). Methods: Twenty-two patients with residual (n=8) or progressive (n=14) advanced NSCLC following chemotherapy and/or radiotherapy received two subcutaneous injections of the optimized TERT 572Y peptide followed by four injections of the native TERT 572 peptide given every 3 weeks. Peptide-specific immune responses were monitored by Elispot assay and/or TERT 572Y pentamer staining. Clinical outcome was compared with that of 22 case-matched historical control patients. Results: Thirteen (59%) out of 22 patients completed the vaccination program. Toxicity consisted primarily of local skin reactions. TERT 572 -specific CD8 + cells were detected in 16 (76.2%) out of 21 patients after the 2nd vaccination and 10 (90.9%) out of 11 patients after the 6 th vaccination. Stable disease occurred in 8 (36.4%) patients with a median duration of 11.2 months. Patients with an early immunological response (n=16) had a significantly longer time to disease progression and overall survival than non-responders (n=5) (log-rank tests p=0.046 and p=0.012, respectively). The estimated median overall survival was 30.0 (range, 2.8–40.0) and 4.1 (range, 2.4–10.9) months for immunological responders and non-responders, respectively. Moreover, median overall survival was 30.6 months (95% CI:10.9–48.9) and 6.1 months (95% CI:4.4–7.8) for the vaccinated and case-matched historical control patients, respectively (p=0.074). Conclusions: TERT 572Y peptide vaccine is well tolerated and effective in eliciting a specific T-cell immunity which seems to be associated with prolonged patients’ survival. No significant financial relationships to disclose.
Adoptive TIL in HPV-negative oral scca
Authors: Rom Leidner, Brendan D Curti, Roxanne M Payne, Walter Urba, Keith S Bahjat, Yoshinobu Koguchi, Krista Nelson, Jennifer A Moore, Marka Crittenden, Yedeh Ying, Ashish Patel, Allen Cheng, Tuan G Bui, Traci Hilton, Christopher Paustian, Sachin Puri, Hong Ming Hu, Carlo Bifulco, Zipei Feng, R Bryan Bell, Bernard Fox
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts A 22 year old male was diagnosed with clinical T2 squamous cell carcinoma of the lateral oral tongue. He underwent partial glossectomy with elective neck dissection of ipsilateral cervical nodes levels I-IV. Pathology showed a 2.1cm primary tumor with clear margins to 5mm, 1.6cm
Renal epithelioid angiomyolipoma
Authors: S. Varma, K. Lacossiere, J. Talwar, F. Forte, M. Dhar
Journal: Journal of Clinical Oncology (2008)

16134 Background: Renal angiomyolipomas are now recognized as neoplasms of clonal origin, showing clonal chromosomal aberrations and originating from a common progenitor cell, the perivascular epithelial cell (PEC). The epithelioid variant of renal angiomyolipoma is a recently identified entity, characterized by predominance of PEC and a unique morphologic and immunohistochemical profile. There is accumulating evidence suggesting that renal epithelioid angiomyolipoma is a malignant disease. Methods: We searched the literature for cases describing the clinical behavior of renal epithelioid angiomyolipoma. A pubmed search was performed using the following keywords: angiomyolipoma, epithelioid, perivascular epithelial cell or/and renal tumors. We recently reviewed a case of fatal renal epithelioid angiomyolipoma at our institution. An experienced pathologist reviewed the histology slides to confirm the diagnosis. Results: Upon review of 133 articles, 38 articles were found eligible for review. We identified ten studies describing twenty cases of renal epithelioid angiomyolipoma. Almost all the cases of renal epithelioid angiomyolipoma identified in the literature, that had follow-up available, died of neoplastic progression of the disease, with liver, lung and bone metastases. Four cases were reclassified as epithelioid angiomyolipomas after retrospective pathology review, and all four were fatal. Three of these had been misdiagnosed as renal cell carcinoma, while one was misdiagnosed as classic renal angiomyolipoma. Conclusions: Unlike classic renal angiomyolipoma, which is commonly benign, renal epithelioid angiomyolipoma behaves in an aggressive manner. It is crucial for the clinician to be aware of and identify the epithelioid variant of renal angiomyolipoma as a malignant disease. It should also be carefully differentiated from renal cell carcinoma. Unlike typical angiomyolipoma, resection alone may not be curative, and perhaps adjuvant therapy should be considered. A possible response to doxorubicin and the potential use of mTOR inhibitors has been recognized in the literature. A multi-modality treatment approach needs to be explored for this newly recognized malignant variant of renal angiomyolipoma. No significant financial relationships to disclose.
Cancer Mortality Among the Polish-Born in the United States
Authors: Jerzy Staszewski, William Haenszel
Journal: JNCI Journal of the National Cancer Institute (1965)

Age-specific cancer death rates for Polish migrants to the United States have been compared with the experience reported for Poland and U.S. native whites. The site-specific displacements in mortality for migrants from those recorded in home and host countries were in general accord with results previously published for 6 other ethnic groups in the United States. Polish migrants continued to display the high stomach cancer risks characteristic of Poland. The low mortality from cancer of the breast, colon, and rectum in Poland directed attention to the upward displacement of risks for these sites among migrants to the level prevailing among U.S. native whites, a sharp contrast to the picture presented for stomach. The death rates for cancer of the esophagus and larynx among male migrants exceeded those prevailing in both countries. The Poles deviated from the pattern for lung cancer set by other ethnic groups, the risks for male migrants following esophagus and larynx in displaying rates higher than those for both native Poles and U.S. native whites, rather than assuming a position intermediate to home and host country.
First case of corporate manslaughter against NHS trust collapses
Authors: Clare Dyer
Journal: BMJ (2016)

A landmark manslaughter prosecution against an NHS trust and a consultant anaesthetist has collapsed, after the judge directed the jury on 28 January to return not guilty verdicts part way through the trial.

Mr Justice Coulson agreed with defence barristers that there was no case to answer against Maidstone and Tunbridge Wells NHS Trust in Kent and a locum consultant anaesthetist, Errol Cornish, in the first corporate manslaughter case to be brought against an NHS trust.

Cornish, 68, was accused of gross …
Mitophagic regulation of myofibroblast differentiation in lung fibroblasts
Authors: Kenji Kobayashi, Jun Araya, Hiromichi Hara, Yusuke Kurita, Saburo Ito, Naoki Takasaka, Satoko Fujii, Shunsuke Minagawa, Jun Kojima, Takanori Numata, Kenichiro Shimizu, Makoto Kawaishi, Yumi Kaneko, Toshiaki Morikawa, Katsutoshi Nakayama, Kazuyoshi Kuwano
Journal: European Respiratory Journal (2014)

Introduction: Contractile myofibroblast accumulation has been implicated in pathological lung remodeling. We have reported the involvement of insufficient autophagy, a process of lysosomal self-degradation, in myofibroblast differentiation. Insufficient mitophagy, the selective autophagic degradation of mitochondria, results in increased reactive oxygen species (ROS) production. ROS is involved in the process of myofibroblast differentiation through the modulation of cell signaling pathways.  Methods: To explore the regulatory role of mitophagy in ROS production and its involvement in myofibroblast differentiation, human lung fibroblasts were used in vitro. Transfection of PINK1 and Parkin siRNA were performed to inhibit mitophagy. DCFH-DA and MitoSOX Red were used to evaluate ROS production, and NAC and MitoTEMPO were employed for inhibition of ROS. Wortmannin and AG1296 were used to inhibit PI3K-Akt pathway and PDGF receptor (PDGFR) tyrosine kinase, respectively.  Results: Inhibition of mitophagy via PINK1 and Parkin knockdown increased mitochondrial ROS production and induced myofibroblast differentiation, which was inhibited by treatment with anti-oxidants. Mitophagy inhibition activated PI3K-Akt pathway, and both wortmannin and Akt1/2 kinase inhibitor abrogated myofibroblast differentiation. PDGFR-mediated signaling was partly responsible for myofibrobalst differentiation in the setting of insufficient mitophagy, as elucidated by anti-oxidants and AG1296 treatments.  Conclusion: These findings suggest insufficient mitophagy-induced ROS production with subsequent PDGFR-PI3K-Akt activation is a potent underlying mechanism for myofibroblast differentiation in the pathogenic sequence of fibrotic lung disorders.
Genetics, Regulation, and Specificity of Murine Natural Antitumor Antibodies and Natural Killer Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Donna A. Chow, Liliana B. Wolosin, Arnold H. Greenberg
 5
Journal: JNCI Journal of the National Cancer Institute (1981)

A concurrent study of specificity, regulation, ontogeny, and genetics of murine natural killer (NK) cell and natural antibody (NAb) activities [in DBA/2, CBA/J, A/Sn, and A/J inbred mice, Bg/Bg and Bg/+ mice of the inbred C57BLl6J background, (C57BL/6 × DBA/2}F1 mice, and (CBA × DBA/2)F1, (A/Sn × DBA/2)F1, and (A/J × DBA/2)F1 mice] revealed that: a) The expressions of NAb and NK cell specificities associated with the YAC-1 tumor were directly related and could not be distinguished on the basis of inhibition and absorption studies, whereas the expressions of the specificities associated with a second NK cell-sensitive tumor, the SL2 lymphoma, were not directly related. b) Treatment of mice with the adjuvants proteose peptone and lipopolysaccharide or the interferon inducers polyinosinic-polycytidylic acid and 2-amino-5-bromo-6-methyl-4-pyrimidinol resulted in increases in NAb levels and NK cells, which suggested that certain aspects of the regulation of these activities may be similar or the same. c) High NK cell activity was codominantly inherited and high serum NAb levels were recessive, which argues against the theory that the NK cell receptor is a passively acquired NAb. d) NK cell activity declined with increasing age in contrast with NAb levels that remained constant throughout adult life. e) Bg/Bg mutants that exhibit an NK cell defect expressed normal levels of NAb. Despite the differences in their genetics, murine antitumor NAb and NK cells bear certain common features-in particular, their response to microbial products and interferon inducers and at least a portion of the antigen repertoire against which they are directed.
Final results of a phase II study of erlotinib, docetaxel and cisplatin in patients with recurrent/metastatic head and neck cancer
Authors: E. S. Kim, M. S. Kies, B. S. Glisson, A. Tsao, L. E. Ginsberg, F. C. Holsinger, B. J. Burke, M. Truong, V. A. Papadimitrakopoulou, S. M. Lippman
Journal: Journal of Clinical Oncology (2007)

6013 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for recurrent/metastatic HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate as single agent in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 intravenously every 3 weeks and erlotinib 150 mg by mouth daily. All agents were started on day 1. Pts were treated with growth factor support. Results: The trial has completed accrual to 50 pts. 47 pts are available for analysis at this time. Median age is 56 years (range 39–72). ECOG PS is 0, 1, 2 (6, 29, 2 pts). 43 pts are evaluable for efficacy. All responses were confirmed via RECIST. Complete responses have been in observed in 4 pts, partial responses in 25 pts and 12 pts have stable disease for an overall response rate of 67% and disease control rate of 95%. After a follow-up of 19 months, median overall survival was 11 months (8.61, 22.5, 95% CI) and progression free survival was 6.01 months (4.37, 8.25). 6 pts had grade 3/4 febrile neutropenia, 4 pts had grade 3/4 dehydration, 3 pts had grade 3 diarrhea, and 2 pts had grade 3/4 GI bleeding. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusions: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in recurrent/metastatic HNSCC. Tissues are being collected and analyzed for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). Final efficacy and biomarker results will be presented at the annual meeting. No significant financial relationships to disclose.
Infant spirometry at three months after birth in term and preterm infants
Authors: Karin Lidberg, Paraskevi Kosma, Gunilla Hedlin, Charlotte Palme-Kilander
Journal: European Respiratory Journal (2011)

Background:  Ex-preterm infants have more airway symptoms in childhood, and forced expiratory flows have been shown to remain low or even diminishing during the first two years after birth in moderately preterm compared to term infants. Questions:Is airway function impaired both in very and moderately ex-preterm babies? Do viral infections affect preterms more severely during the first year?   Methods:  110 term and 150 preterms, born at 27+0 – 33+6 weeks gestation, were examined with infant spirometry during tidal breathing at term and with raised volume forced expiration in Jaegher Baby box at three months after birth. Nasopharyngeal viral swabs were taken during all URI and LRI during the first year. New spirometry will be performed at 18 months after birth, corrected for prematurity.   Results:  Babies born at 27-31 weeks gestation had lower FVC, FEV 0,4 and FEV 0,5 compared to term infants of the same gender (p   Conclusions:  Very preterm (GA
Survival of women with metastatic breast cancer at Yale from 1920 to 1980.
Authors: M Todd, M Shoag, E Cadman
Journal: Journal of Clinical Oncology (1983)

The tumor registry at Yale--New Haven Hospital, which began recording data in 1920, was utilized to examine the ultimate outcome of all breast cancer patients who were initially diagnosed at Yale with metastatic breast cancer. Of the 5,898 patients with breast cancer seen from 1920 to 1980, 574 initially had metastatic cancer. The median survival of these patients increased steadily from 21 months in 1920 to 41 months in the decade from 1970 to 1980. The percentage of women actually surviving 5 years increased from 5% in the 1920s to approximately 25% in the 1960s. Despite the use of combination drug programs in the 1970s, the percentage of these patients remaining alive at 5 years remained near 25%. Firm conclusions cannot be made from a retrospective study spanning 60 years, although the trends depicted and lack of continued improvement indicate that our current therapeutic approach to metastatic breast cancer may not result in dramatic improvement in overall survival.
Cancer in human immunodeficiency virus-infected children: a case series from the Children's Cancer Group and the National Cancer Institute.
Authors: M O Granovsky, B U Mueller, H S Nicholson, P S Rosenberg, C S Rabkin
Journal: Journal of Clinical Oncology (1998)

PURPOSE To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors. METHODS We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer Institute (NCI) for cases of cancer that occurred between July 1982 and February 1997 in children who were HIV seropositive before or at the time of cancer diagnosis. We used Kaplan-Meier survivorship curves, hazard function estimates, and Cox proportional hazards models to evaluate survival. RESULTS Sixty-four children (39 boys, 25 girls) with 65 tumors were reported. Thirty-seven children (58%) acquired HIV infection vertically (median age at cancer diagnosis, 4.3 years); 22 children (34%) acquired HIV through transfusion of blood or blood products (median age at cancer diagnosis, 13.4 years). Forty-two children (65%) had non-Hodgkin's lymphoma (NHL). Eleven children (17%) had leiomyosarcomas (or leiomyomas), which are otherwise exceptionally rare in children. Other malignancies included acute leukemia (five children), Kaposi's sarcoma (KS; three children), Hodgkin's disease (two children), vaginal carcinoma in situ (one child), and tracheal neuroendocrine carcinoma (one child). Median survival after NHL diagnosis was 6 months (range, 1 day to 89 months) and after leiomyosarcoma was 12 months (range, 10 days to 19 months). The average monthly death rate after NHL diagnosis was 12% in the first 6 months, which decreased to about 2% thereafter. In contrast, the monthly death rate after leiomyosarcoma diagnosis increased from 5% in the first 6 months to about 20% thereafter. CONCLUSION After NHL, leiomyosarcoma is the second leading cancer in children with HIV infection. Both cancers have high mortality rates; improved outcome for NHL, in particular, may depend on earlier diagnosis and therapy.
Serum and salivary IgG and IgA antibodies to desmoglein 3 in mucosal pemphigus vulgaris
Authors: S. Ali, C. Kelly, S.J. Challacombe, A.N.A. Donaldson, B.S. Bhogal, J.F. Setterfield
Journal: British Journal of Dermatology (2016)

The use of saliva for the diagnosis of pemphigus vulgaris (PV) by enzyme-linked immunosorbent assay (ELISA) using desmoglein (Dsg)3 antigen has not been extensively documented, nor has the detection of serum IgA antibodies to Dsg3.(i) To establish whether whole saliva might provide a suitable alternative to serum for diagnosing and monitoring PV; (ii) to investigate whether anti-Dsg3 IgA antibodies can be detected in serum and saliva and (iii) to establish whether there is an association between serum or saliva anti-Dsg3 antibodies and disease severity.Precoated Dsg3 ELISA plates were used to test serum and/or saliva for IgG and IgA antibodies. Matched serum and whole saliva samples were collected from 23 patients with PV, 17 healthy subjects and 19 disease controls. All patients with PV, disease controls and six healthy controls provided matched parotid saliva.Whole saliva IgG antibodies to Dsg3 were detected in 14 of 23 patients (61%) and serum IgG antibodies were detected in 17 of 23 (74%) with a strong positive correlation. Serum IgA antibodies were detected in 14 of 23 patients with PV (61%) with a combined positivity (IgG and/or IgA antibodies to Dsg3) of 78% (18 of 23). We were unable to show IgA anti-Dsg3 antibodies in either whole or parotid saliva of patients with PV. Sequential samples showed that changes in IgG antibody titres in whole saliva were associated with a change in disease severity scores.Assay of salivary IgG antibodies to Dsg3 offers a diagnostic alternative to serum in the diagnosis and monitoring of PV. The role of anti-Dsg3 IgA antibodies requires further elucidation in the pathogenesis of PV.
Does protein supplementation enhance the effects of resistance training in patients with COPD
Authors: Linzy Houchen, Manoj Menon, Samantha Harrison, Carolyn Sandland, Michael Morgan, Sally Singh, Michael Steiner
Journal: European Respiratory Journal (2011)

Introduction: Protein supplementation (PS) & resistance training (RT) enhances muscle growth in healthy elderly subjects. Its role in patients with COPD is unknown.

Hypothesis: Adding PS to RT will yield greater increases in function than RT alone.

Method: We conducted a randomised, double-blind, placebo controlled trial. 59 patients [mean (SD) age 67.9 (9.1)yr, BMI 26.7 (2.7), FEV146.8 (17.6)% pred, 36men] completed 8weeks of quadriceps RT. Training was 5x30 bilateral knee extensions; 3 times/week on an isokinetic dynamometer (Cybex: speed=180°/sec). Subjects received PS or placebo after each RT session. Isometric & isokinetic quadriceps strength at 60°/sec [Cybex: Newton-meters (Nm)], thigh lean mass [DEXA: grams (g)] & incremental cycle performance [peak work (W) & peak oxygen uptake (VO2: mls/kg/min)] were assessed at baseline & 8 weeks.

Results: Table1 shows mean change from baseline and between group differences for all outcomes. There were significant within group changes in all outcomes in both groups (except peak VO2 in the PS group). There were no significant differences between groups.

View this table:

Table1





Conclusion: There were significant improvements in quadriceps strength, thigh mass & whole-body cycle work following RT. The addition of PS did not augment the functional benefits of RT.