tbuckley/cabot-search huggingface dataset:
A large cohort study of clinical outcomes and prognostic predictors in patients with acute exacerbation of idiopathic pulmonary fibrosis
Authors: Seishu Hashimoto, Yoshio Taguchi, Takashi Hajiro, Ikkoh Yasuda, Yoshiki Ishii, Masahito Ebina, Kazuma Kishi, Hiroyuki Taniguchi, Takafumi Suda, Sakae Homma, Yukihiko Sugiyama
Journal: European Respiratory Journal (2014)

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has been well documented. However, there are a few reports about its clinical outcomes and prognostic predictors.  Objectives: To assess clinical outcomes and prognostic predictors in patients with AE-IPF in a multi-institutional cohort.  Methods: We retrospectively analyzed 215 consecutive patients who had a diagnosis of AE-IPF between January 2011 and December 2012 at 68 hospitals in Japan. AE-IPF was defined using the revised Japanese criteria. The clinical features, and clinical outcomes and prognostic predictors of AE-IPF were investigated.  Results: The overall, 30-day and 90-day mortality rate were 67.0%, 27.4% and 44.7%, respectively. The median survival of patients with AE-IPF was 102 days (95% CI, 74 to 154 days). C reactive protein, lactate dehydrogenase (LDH) and D-dimer in non-survivors at the time of AE were significantly higher than in survivors. In non-survivors at stable status of IPF just before AE, the modified Medical Research Council (mMRC) dyspnea scale was higher, and forced vital capacity (FVC) was lower than in survivors. The initial management was effective in survivors compared with non-survivors. The multivariate Cox analysis revealed that high LDH at the time of AE, and high mMRC dyspnea scale and low FVC at stable status of IPF just before AE were three meaningful predictors of poor survival. The effectiveness of the initial management of AE was related survival.  Conclusions: The outcome of AE-IPF was still poor, but better than predicted. Understanding possible prognostic factors could contribute to the better management of AE-IPF.
Noninvasive detection of EGFR T790M mutation in gefitinib resistant non-small cell lung cancer using mutant-enriched PCR
Authors: Chen He, Lixia Zheng, Yuzhong Xu, Ming Liu, Yuanguang Li, Jun Xu
Journal: European Respiratory Journal (2013)

Epidermal growth factor receptor ( EGFR ) T790M mutation has been reported in non-small cell lung cancer (NSCLC) patients with acquired resistance to the tyrosine kinase inhibitors (TKIs). However, the tissue availability and technical feasibility limits the pre-therapeutic genotyping of  EGFR  T790M mutation in a clinical setting. The current study is, therefore, designed to develop a blood-based approach to detect the  EGFR  T790M mutation in advanced NSCLC patients. Plasma samples from 33 NSCLC patients treated with gefitinib were subjected to mutant-enriched PCR and direct sequencing. The results showed the mutant-enriched PCR could successfully detect the T790M mutation in patient samples with drug resistance. The mutant-enriched PCR were able to detect one mutant in the presence of 1×10 3  wild-type genes. Furthermore, the detection rate was higher using mutant-enriched PCR (36.4%) than that using direct sequencing (6.1%). Mutations were more frequent in post-treatment samples (36.4%) than that in pre-treatment samples (6.1%). Those with  EGFR  T790M mutation have a better prior gefitinib response compared to those without  EGFR  T790M mutation. These results suggest that the blood-based mutant-enriched PCR is an ideal noninvasive monitoring system for detecting  EGFR  T790M mutation for clinical application.
<i>The Doctor</i>: For Life and at the End of Life
Authors: Joseph Kash
Journal: Annals of Internal Medicine (2015)

Letters2 June 2015The Doctor: For Life and at the End of LifeJoseph Kash, MDJoseph Kash, MDFrom Edward Hospital, Naperville, Illinois.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5080 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I share Pizzo's concerns (1) about handing off patients and, in a sense, wiping our hands free as these patients enter a different phase of their life with their illness. I am a medical oncologist and have noticed a change in the past few years where the hospice programs seem to pressure me to hand the care off to the hospice palliative care physician.I have always told patients that hospice will be my eyes and ears, but I will still be the captain of the ship. I now feel like this is a lie. Hospice services ...Reference1. Pizzoy PA. The Doctor: for life and at the end of life. Ann Intern Med. 2015;162:228-9. [PMID: 25486216] doi:10.7326/M14-2399 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Edward Hospital, Naperville, Illinois.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L15-0136. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Doctor: For Life and at the End of Life Philip A. Pizzo The Doctor: For Life and at the End of Life Philip A. Pizzo The Doctor: For Life and at the End of Life Joanne Lynn The Doctor: For Life and at the End of Life Joanne Lynn Metrics 2 June 2015Volume 162, Issue 11Page: 804KeywordsConflicts of interestDisclosureHospitalistsPalliative care ePublished: 2 June 2015 Issue Published: 2 June 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
High grade cervical lesions decline in young US women
Authors: J. Wise
Journal: BMJ (2015)

The incidence of high grade cervical lesions in young women in the United States has fallen, a new analysis has found. The researchers reported in the journal Cancer that this may be caused by the introduction of the human papillomavirus (HPV) vaccine but may also be due to changes in screening guidelines.1

From 2008 to 2012, 9119 cases of high grade cervical lesions (CIN2+) were reported among 18 to 39 year olds as part of a sentinel system for the US Centers for Disease Control and Prevention.

In all four catchment areas the researchers found a dramatic and consistent decrease in the incidence of high grade lesions among women aged 18 …
What is the correlation between Nottingham score and receptor status in malignant breast cancer
Authors: Mehrdad Mokri, Masoumeh Guity, Siamak Shariat Torbaghan, Mostafa Bagerzade, Morteza Atri
Journal: Clinical Cancer Research (2006)

A32   Objective: The Nottingham score(NS), a histological grading system for invasive breast carcinoma include by; Tubule formation, Nuclear pleomorphism and Mitotic rate as criteria and each are assigned 1,2 or 3 points and the scores are added for a combined histological score. Tumors are graded based on the combined score into grade I(3-5;well differentiated), grade II(6-7,moderately differentiated) and grade III(8-9 poorly differentiated). Hormones receptors (ER and PR) and Her-2/neu gene or its protein are now routinely evaluated in all breast cancer cases. Her-2/neu over expression is associated with features of a poor prognosis like high tumor grade and S- phase fraction, nodal metastasis and estrogen(ER) and progesterone receptor (PR) negativity. Its over expression produces ligand independent down regulation of ER. The reduced hormone receptor expression might be one of the mechanism by which Her-2/neu positive tumors show a decreased response to hormonal agents and decreased DFS.Methods: The data on all women reviewed pathology reports Invasive ducat carcinoma of breast in our community hospital were retrospectively analyzed. The final analysis had 420 patients. The receptor status and NS were tabulated. We divided all the patients into Her-2/neu positive 185 and negative 235 and later subdivided into hormone receptor (both ER and PR) negative or positive (ER or PR).Results: Her2/neu neg, ER or PR (+ ) in NS 3-5, NS 6-7 and NS 8-9 arrengment by: 3(5.5%), 11(40.3%) and 10(34.4%).Her2/neu neg, ER and PR(-) in NS 3-5, NS 6-7 and NS 8-9 arrengment by: 7(4.9%), 17(11.9%) and 30(21%).Her2/neu pos, ER or PR (+) in NS 3-5, NS 6-7 and NS 8-9 arrengment by: 4(8.2%), 6(26.9%) and 9(47.6%).Her2/neu pos, ER and PR (-) in NS 3-5, NS 6-7 and NS 8-9 arrengment by: 5(3.1%), 15(9.4%) and 37(23.1%).Conclusion: In this study it is observed that ER or PR positivity shows a trend towards lower NS. The patents with triple receptor negative status had higher NS. This suggests a correlation between NS, receptor status and DFS.
Long‐Term Safety and Efficacy of Budesonide Nasal Aerosol in Perennial Rhinitis
Authors: N. Lindqvist, V. H. Balle, P. Karma, J. Kärjä, D. Lindström, J. Mäkinen, J. Pukander, P. Ruoppi, J. Suonpää, W. ÖStlund, U. Pipkorn
Journal: Allergy (1986)

A long‐term safety study of intranasally administered budesonide, a topical glucocorticoid, has been performed. 104 patients with perennial rhinitis, allergic or non‐allergic, participated in a multicentre study in seven ENT‐clinics utilising an identical protocol. A budesonide dosage of 400 μg/day was used as starting dose, but the patients were at liberty to reduce the daily dose to 200 μg. The patients were observed at intervals up to 12 months. At the entry and follow‐up visits the following parameters were recorded: rhinoscopic findings, nasal symptom scores, blood chemistry, hematology, urinalysis and determination of plasma cortisol levels before and after stimulation with ACTH (Synacthen®). Nasal biopsies taken from 50 of the patients at the beginning and completion of the study were examined in a blinded way by an indepndent pathologist. The analysis revealed no histopathological changes of the nasal mucosa. At rhinoscopy no signs of atrophy or Candida were reported. Lividity of the nasal mucosa was significantly reduced during the trial, which was also the case for nasal congestion and secretion. All nasal symptom parameters assessed by the patients were significantly reduced from baseline during the follow‐up period. No clinically significant changes in the hematological and blood chemistry parameters were observed. Plasma cortisol analysis before and after challenge with ACTH revealed no influence on the hypothalamic pituitary adrenal axis. No tachyphylaxis was observed; on the contrary, there was a clear tendency for reduction of the daily dose of budesonide necessary to keep the patients symptom‐free. The present study suggests that intransal budesonide in the dose of 400 μg/day is a safe and valuable addition to our therapeutic armory for perennial rhinitis.
The Cellular and Molecular Basis of Translational Immunometabolism
Authors: Giuseppe Danilo Norata, Giuseppina Caligiuri, Triantafyllos Chavakis, Giuseppe Matarese, Mihai Gheorge Netea, Antonino Nicoletti, Luke A.J. O’Neill, Federica M. Marelli-Berg
Journal: Immunity (2015)
Frequencies of ALK and ROS in NSCLC FFPE tumor samples utilizing a highly specific immunohistochemistry-based assay and FISH analysis.
Authors: V. Rimkunas, K. Crosby, M. Kelly, M. Silver, K. Hincman, R. Polakiewicz, D. Li, X. Zhou, H. Haack
Journal: Journal of Clinical Oncology (2010)

10536 Background: Receptor tyrosine kinases ALK and ROS are expressed as oncogenic fusion proteins in approximately 2%-5% of all non-small cell lung cancer (NSCLC) patients. Most recently, ALK targeted therapies have been shown to be effective in ALK positive patients. This may also be true for ROS but is less validated. The ability to identify patients that harbor these fusion proteins is desirable. Currently, molecular assays such as fluorescence in situ hybridization (FISH) and RT-PCR are used to identify these patients. We reasoned that an immunohistochemistry (IHC)-based assay could provide a fast, inexpensive alternative for diagnosing patients with ALK and ROS abnormalities. We have developed an IHC-based assay for the detection of low level ALK and ROS in NSCLC patients with high specificity and sensitivity. Methods: We generated highly specific rabbit monoclonal antibodies against ALK and ROS. ALK and ROS antibodies were evaluated in a panel of 656 NSCLC FFPE tumor tissues. The majority of tissues (n = 409) were analyzed in tissue microarray format while the remaining (n = 247) were whole tissue sections. IHC positive tissues were also analyzed by FISH to compare protein expression to the presence of ALK and ROS rearrangements. Results: Western blot, IHC and FISH experiments confirm that our monoclonal antibodies can specifically detect low levels of both ROS and ALK in NSCLC tumor samples. Approximately, 4.1% (27 cases) of NSCLC cases analyzed were ALK positive by IHC. We were able to confirm these results by FISH in 25/27 cases. The remaining 2 cases we were unable to score due to poor tissue quality. We identified 2.6% (17/656) of the NSCLC tissues to be ROS positive by IHC. We confirmed these results in 16/17 tissues by FISH analysis. Due to technical issues, we were unable to score the remaining tissue. Both the ALK and ROS antibodies are highly specific. We are currently performing additional studies to determine sensitivity. ALK and ROS were never observed in the same tumor sample. Conclusions: We conclude that IHC staining with ALK and ROS monoclonal antibodies is a highly specific assay that reliably identifies aberrant ALK and ROS protein expression in NSCLC patients. No significant financial relationships to disclose.
Sex Differences in Platelet Reactivity and Cardiovascular and Psychological Response to Mental Stress in Patients With Stable Ischemic Heart Disease
Authors: Zainab Samad, Stephen Boyle, Mads Ersboll, Amit N. Vora, Ye Zhang, Richard C. Becker, Redford Williams, Cynthia Kuhn, Thomas L. Ortel, Joseph G. Rogers, Christopher M. O’Connor, Eric J. Velazquez, Wei Jiang
Journal: Journal of the American College of Cardiology (2014)
Randomized Phase III Study Comparing Conventional-Dose Doxorubicin Plus Ifosfamide Versus High-Dose Doxorubicin Plus Ifosfamide Plus Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Advanced Soft Tissue Sarcomas: A Trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group
Authors: A. Le Cesne, I. Judson, D. Crowther, S. Rodenhuis, H.J. Keizer, Q. Van Hoesel, J.Y. Blay, J. Frisch, M. Van Glabbeke, C. Hermans, A. Van Oosterom, T. Tursz, J. Verweij
Journal: Journal of Clinical Oncology (2000)

PURPOSE: This randomized multicenter study was designed to compare the activity of a high-dose doxorubicin-containing chemotherapy regimen with a conventional standard-dose regimen in adult patients with advanced soft tissue sarcomas (ASTS). PATIENTS AND METHODS: Between 1992 and 1995, 314 patients were randomized to receive a standard-dose regimen (arm A), containing doxorubicin (50 mg/m 2 on day 1) and ifosfamide (5 g/m 2 on day 1), or an intensified regimen (arm B), combining doxorubicin (75 mg/m 2 on day 1), the same ifosfamide dose, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim, 250 μg/m 2 on days 3 to 16); all courses were repeated every 3 weeks. RESULTS: The median age of the 294 eligible patients was 50 years. They received a median of five chemotherapy cycles. The median dose and relative doxorubicin dose-intensity achieved were 245 mg and 97% in arm A and 360 mg and 99% in arm B, respectively. Thirty-eight percent and 23% of patients presented with leiomyosarcomas and liver metastases, respectively. Objective responses were observed in 31 (21%) of 147 assessable patients in arm A and in 31 (23.3%) of 133 in arm B (P = .65). No change was observed in 41.6% and 46.2% of patients in arm A and B, respectively. Progression-free survival (PFS) was significantly longer in the intensive arm (P = .03). The median duration of the time to progression was 19 weeks in the conventional arm and 29 weeks in the intensified arm. There was no difference in overall survival (P = .98) between the two therapeutic arms. Toxicities were manageable in both arms. A grade 3/4 neutropenia and infection occurred in 92% and 4.6% of patients in arm A, respectively, and in 90% and 16.6% in arm B, respectively. Grade 3/4 thrombocytopenia was more frequent in arm B. CONCLUSION: The use of rhGM-CSF allowed safe escalation of chemotherapy doses. Despite a 50% increase of the doxorubicin dose-intensity, the high-dose regimen failed to demonstrate any impact on survival in patients with ASTS. The low complete response rate, the high incidence of leiomyosarcomas, and liver metastases may in part explain these results. However, the lengthening of the PFS in the intensive arm, because of the quality of stable disease and inappropriate tumor evaluation policies that potentially lead to an underestimation of antitumor activity, does not definitively refute the use of a high-dose chemotherapy regimen in selected patients with ASTS.
Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma
Authors: Christine E. Brown, Behnam Badie, Michael E. Barish, Lihong Weng, Julie R. Ostberg, Wen-Chung Chang, Araceli Naranjo, Renate Starr, Jamie Wagner, Christine Wright, Yubo Zhai, James R. Bading, Julie A. Ressler, Jana Portnow, Massimo D'Apuzzo, Stephen J. Forman, Michael C. Jensen
Journal: Clinical Cancer Research (2015)

Abstract Purpose: A first-in-human pilot safety and feasibility trial evaluating chimeric antigen receptor (CAR)–engineered, autologous primary human CD8+ cytotoxic T lymphocytes (CTL) targeting IL13Rα2 for the treatment of recurrent glioblastoma (GBM). Experimental Design: Three patients with recurrent GBM were treated with IL13(E13Y)-zetakine CD8+ CTL targeting IL13Rα2. Patients received up to 12 local infusions at a maximum dose of 108 CAR-engineered T cells via a catheter/reservoir system. Results: We demonstrate the feasibility of manufacturing sufficient numbers of autologous CTL clones expressing an IL13(E13Y)-zetakine CAR for redirected HLA-independent IL13Rα2-specific effector function for a cohort of patients diagnosed with GBM. Intracranial delivery of the IL13-zetakine+ CTL clones into the resection cavity of 3 patients with recurrent disease was well-tolerated, with manageable temporary brain inflammation. Following infusion of IL13-zetakine+ CTLs, evidence for transient anti-glioma responses was observed in 2 of the patients. Analysis of tumor tissue from 1 patient before and after T-cell therapy suggested reduced overall IL13Rα2 expression within the tumor following treatment. MRI analysis of another patient indicated an increase in tumor necrotic volume at the site of IL13-zetakine+ T-cell administration. Conclusions: These findings provide promising first-in-human clinical experience for intracranial administration of IL13Rα2-specific CAR T cells for the treatment of GBM, establishing a foundation on which future refinements of adoptive CAR T-cell therapies can be applied. Clin Cancer Res; 21(18); 4062–72. ©2015 AACR.
A randomized trial of two etoposide schedules in small-cell lung cancer: the influence of pharmacokinetics on efficacy and toxicity.
Authors: P I Clark, M L Slevin, S P Joel, R J Osborne, D I Talbot, P W Johnson, R Reznek, T Masud, W Gregory, P F Wrigley
Journal: Journal of Clinical Oncology (1994)

PURPOSE Etoposide is a schedule-dependent drug, as demonstrated by the superiority of 5 consecutive daily infusions over a continuous 24-hour infusion in patients with small-cell lung cancer. A randomized trial has therefore been conducted to compare an extended 8-day regimen with the 5-day schedule. PATIENTS AND METHODS Ninety-four patients with small-cell lung cancer (35 limited disease, 59 extensive disease) were randomized to receive single-agent etoposide 500 mg/m2, either as 5 daily 2-hour infusions of 100 mg/m2 or as 8 daily 75-minute infusions of 62.5 mg/m2, both repeated every 3 weeks for six cycles. Single-agent carboplatin was administered at relapse in both arms of the study. Patients were stratified at randomization according to extent of disease and Karnofsky performance status (KPS). RESULTS The overall response rate was 81% in the 5-day arm and 87% in the 8-day arm, with median survival durations of 7.1 and 9.4 months, respectively (no significant differences). The time over which plasma etoposide exceeded low plasma concentrations was significantly longer in patients who responded compared with patients who did not respond. This was most significant for time at concentrations greater than 1, 1.5, and 2 micrograms/mL. Hematologic toxicity was significantly worse in the 5-day arm of the study (cycle no. 1 nadir neutrophil count, 0.8 x 10(9)/L v 1.7 x 10(9)/L). Stepwise regression analysis found duration of exposure to plasma etoposide greater than 3 micrograms/mL to be predictive of nadir neutrophil count and duration of exposure to plasma etoposide greater than 2 micrograms/mL to be predictive of nadir WBC count. CONCLUSION The 5-day and 8-day regimens had equivalent activity in small-cell lung cancer. A pharmacokinetic association between concentrations of etoposide and response and toxicity was found. Antitumor activity was associated with the maintenance of lower levels of etoposide than found to be associated with hematologic toxicity. This supports the hypothesis that the schedule of etoposide administration may affect efficacy and toxicity, and that prolonged exposure to low concentrations of etoposide may improve the therapeutic ratio for this drug.
Comprehensive analysis of the PTEN domains on TGFβ-induced aberrant cell motility in lung alveolar/epithelial cells by using PTEN constructs with deletion mutants
Authors: Naozumi Hashimoto, Masaaki Kusunose, Daisuke Aoyama, Motohiro Kimura, Yoshinori Hasegawa
Journal: European Respiratory Journal (2014)

We recently showed that TGFβ-induced phosphorylation of the PTEN C-terminus might induce EMT and aberrant cell motility and that modulation of the PTEN C-terminus blocked these pathological phenotypes (Plos One 8(11):e81133.2013). But, we have not yet determined the exact mechanism, by which modulation of the PTEN C-terminus could show the inhibitory effect on aberrant cell motility. Therefore, this study is aimed to evaluate it, by using several PTEN constructs with deletion mutants. Four kinds of deletion mutants in the phosphatase domain, the C2 domain, and/or the PTEN C-terminus were prepared. And then, we established lung alveolar/epithelial cells with a Dox-dependent gene expression system, in which each these mutant is induced only when Dox is added. The effect of these PTEN constructs on TGFβ-induced cell aberrant motility was evaluated, by using migration assay. Migration assay suggested that both of the phosphatase and C2 domains might be essential to inhibit TGFβ-induced cell aberrant motility via the protein and lipid phosphatase activities. Furthermore, deletion of the PTEN C-terminus showed partial inhibition of the cell motility although the PTEN mutant retains the phosphatase activities. PTEN is newly classified as an intrinsically disordered protein (IDP) and the PTEN C-terminus is identified as the functional intrinsically disordered region that confers PTEN primary and secondary interactomes and dictates the majority of PTEN functions. Comprehensive analysis of PTEN as IDP gives us the new clue to control TGFβ-induced pathological phenotypes in lung alveolar/epithelial cells.