tbuckley/cabot-search huggingface dataset:
An evaluation of clinical pharmacy services in hematology/oncology out-patient setting
Authors: S. R. Shah, J. Dowell, P. Wilson, R. Hughes
Journal: Journal of Clinical Oncology (2004)

6109 Background: VA North Texas Health Care System, Dallas, TX provides a unique opportunity for a clinical pharmacist to work as a provider. Clinical pharmacists provide services under specific Scope of Practice document. Even though clinical pharmacists are actively involved in patient care, many clinical pharmacy efforts remains undocumented, resulting in underestimation of the importance of clinical pharmacy services and missed opportunity for improvement and new direction. The purpose of this project was to document and evaluate the services of hematology/oncology clinical pharmacy in the out-patient setting. Methods: Pendragon Forms 3.2 software was utilized to design documentation template. The template was designed to collect diagnoses, supportive care issues, drug specific interventions and prescriptions written. This template was uploaded to the Personal Digital Assistant (PDA) for documentation. Patient specific information was documented in password protected PDA by the hematology/oncology pharmacist or pharmacy residents. Data collected from November 1st, 2002 to October 31st, 2003 were retrospectively analyzed. Results: Clinical pharmacists had 423 patient visits for chemotherapy follow-up or disease management. Clinical pharmacists saw on average 35.25 patients per month. Patient diagnoses included colon-rectal cancer (23%), multiple-myeloma (14%), non-small cell lung cancer (13%), chronic lymphocytic leukemia (10%), myelodysplastic syndromes (5%), chronic myelogenous leukemia (4%) and non-Hodgkin's lymphoma (4%). During 423 patient visits, 342 supportive care issues were addressed such as anemia (34%), pain (22%), constipation/diarrhea (15%) and nausea/vomiting (8%). Major drug specific interventions included drug addition (41%), discontinuation (23%) and adjustment (21%). Clinical pharmacists were actively involved in prescribing medications. 445 prescriptions were filled, of which 181 were new, 150 were renewed and 114 were refilled. Conclusions: This is the first study to document the considerable contribution that clinical pharmacist can make to the care of oncology patients. No significant financial relationships to disclose.
Manifestation and prognostic value of EBV serology in nasal/nasopharyngeal T and NK-cell lymphomas
Authors: Y. Zhang, Y. Huang, J. Xiao, Y. Xia, T. Lu, T. Lin
Journal: Journal of Clinical Oncology (2006)

7596 Background: Extranodal nasal type T and NK-cell lymphoma is highly associated with the Epstein-Barr virus (EBV) infection which is usually found in tumor cells, but the serum manifestation of EBV and its prognostic value remains unclear. Methods: 151 patients with nasal/nasopharyngeal T and NK-cell lymphomas were reviewed, the diagnoses of which were confirmed by histology and immunohistochemistry from Jan, 1992 to Nov, 2004. In 40 patients, which included 30 males and 10 females and aged 24 to 73(median 46) years old, analyses were performed of serum titers of antibodies against virus-capsid antigen (VCA-IgA) and early antigen (EA-IgA) with immunoenzyme assay, and antibody against EBV DNAase (EDAb), with immunoradiological method. Positive criteria were identified as VCA-IgA ≥ 1: 10, EA-IgA≥ 1: 10, and EDAb ≥ 30%. Clinically, 87.5% of the 40 patients were staged as Ann Arbor I and II diseases. Most patients underwent combined chemo and radiotherapy. Results: Median follow-up time for survived patients was 17(6–136) months. Median survival time for the overall patients were 12 months. Highest serum VCA-IgA, EA-IgA, and EDAb levels were 1: 1280, 1: 40, and 86% respectively. Positive rates of the three parameters were 60%, 15%, and 50% respectively. 30 patients(75%) had at least one positive parameter. Positve EA-IgA was negatively correlated with survival (p=0.0245) in Kaplan-Meier analysis, neither positive VCA-IgA or elevated EDAb level showed significant correlation with survival (p=0.134 and 0.405 ). Conclusions: Most patients with nasal/nasopharyngeal T and NK-cell lymphomas showed serum evidences of EBV infection, higher EA-IgA level can be a poor prognostic factor for survival. The importance of EBV serology in patients with nasal/nasopharyngeal T and NK-cell Lymphoma deserves further investigation. No significant financial relationships to disclose.
The E3 Ubiquitin Ligases Siah2 Contributes To Imatinib Resistance In Chronic Myeloid Leukemia In Hypoxia Condition
Authors: Na Xu, Xiaozhen Xiao, Yajuan Xiao, Xuan Zhou, Guanlun Gao, Fen Huang, Dan Xu, Hongsheng Zhou, Bing Xu, Liu Xiaoli
Journal: Blood (2013)
Abstract 13974: The Use of Allogeneic Mesenchymal Stromal Cells to Refine the Emerging "Cell-Sheet" Technique for the Treatment of Heart Failure
Authors: Nobuko Tano, Masahiro Kaneko, Chiho Ikebe, Steven R Coppen, Manabu Shiraishi, Yasunori Shintani, Ken Suzuki
Journal: Circulation (2013)

We have reported that epicardial placement of cell-sheets composed of bone marrow mesenchymal stromal cells (MSCs) markedly increases donor MSC survival and amplifies paracrine effects, thereby augmenting therapeutic benefits, compared to the current cell-delivery method. It is also suggested that allogeneic MSCs may be useful for cell therapy without immunosuppression. We thus examined immune rejection and therapeutic effects of allogeneic MSC-sheets for heart failure. Methods & Results: Flow cytometory and qRT-PCR showed that expression of MHC class I and II in rat MSCs was lesser than that of unfractionated bone marrow cells. Four weeks after coronary artery ligation, female Lewis rats underwent placement of sheets composed of 4 million MSCs from male Lewis rats (Auto group) or Fisher rats (Allo group) generated using temperature responsive dishes, or sham treatment (Cont group). Up to day 3 post treatment, Allo MSCs survived similarly to the Auto MSCs (Table), leading to analogous myocardial upregulat...
SOX4 Is Essential for Prostate Tumorigenesis Initiated by PTEN Ablation
Authors: Birdal Bilir, Adeboye O. Osunkoya, W. Guy Wiles, Soma Sannigrahi, Veronique Lefebvre, Daniel Metzger, Demetri D. Spyropoulos, W. David Martin, Carlos S. Moreno
Journal: Cancer Research (2016)

Abstract Understanding remains incomplete of the mechanisms underlying initiation and progression of prostate cancer, the most commonly diagnosed cancer in American men. The transcription factor SOX4 is overexpressed in many human cancers, including prostate cancer, suggesting it may participate in prostate tumorigenesis. In this study, we investigated this possibility by genetically deleting Sox4 in a mouse model of prostate cancer initiated by loss of the tumor suppressor Pten. We found that specific homozygous deletion of Sox4 in the adult prostate epithelium strongly inhibited tumor progression initiated by homozygous loss of Pten. Mechanistically, Sox4 ablation reduced activation of AKT and β-catenin, leading to an attenuated invasive phenotype. Furthermore, SOX4 expression was induced by Pten loss as a result of the activation of PI3K–AKT–mTOR signaling, suggesting a positive feedback loop between SOX4 and PI3K–AKT–mTOR activity. Collectively, our findings establish that SOX4 is a critical component of the PTEN/PI3K/AKT pathway in prostate cancer, with potential implications for combination-targeted therapies against both primary and advanced prostate cancers. Cancer Res; 76(5); 1112–21. ©2015 AACR.
Rare ovarian cancers (ROC) in France: Analysis of the first 100 patients (pts) prospectively included through an on-line observatory
Authors: I. L. Ray-Coquard, J. P. Guastalla, J. P. Lotz, B. Weber, D. Mayeur, H. Orfeuvre, J. Provencal, E. Guardiola, D. Paraiso, E. Pujade-Lauraine
Journal: Journal of Clinical Oncology (2008)

16506 Background: A website (www.ovaire-rare.org) dedicated to germ cell and sex cord-stromal malignant tumors was developed in France to collect clinical cases and tumor samples of these uncommon ovarian cancers. The ultimate goal of this website is to better assess clinical and biological prognosis factors of ROC and to evaluate medical practice in the country. Methods: Adult pts with histological diagnosis of ROC in first-line or in first relapse were eligible. Results: From 03/2002 to 12/2007, 157 pts have been included and the first 100 were evaluated. Pts characteristics were: inclusion at diagnosis (78 pts) or in first relapse (22), histology: sex cord-stromal (61%), germ cell (30%), others (5%), median age 44 y. (range 18–79), median tumor size 12 cm (range 1–30), FIGO stage I 73%, II 10%, III 14%, IV 3%, ECOG PS 0 (88%). Review of histology by a panel was performed for 66 pts with discrepancy from initial diagnosis in 36%. Pts had initial conservative surgery in 56% and only 10% had lymph node dissection. 56 pts received BEP regimen (35 in first line, 13 in relapse). Grade 3–4 toxicity was observed in 26% of pts with 1 toxic death. Relapse occurred in 11/78 pts in first line and 5 died. OS at 5y was 94% and median PFS were 64 months (0–332). Independent prognostic factors for PFS were histology (other vs. germ cell or stromal; p=0.04), age (<60y vs. ≥60, p=0.03), stage (I/II vs. III/IV, p0.008), previous pregnancy (yes vs. no, p=0.04) and tumor size (<10 or >10cm, p=0.04). No patient in first line relapsed in optimal surgery subgroup compared to 16% for “other” surgery, p=NS. Conclusions: This on-line observatory on ROC offers an unique opportunity to better assess medical practice for these tumors in France. The histological discrepancies between initial diagnosis and second opinion confirm the importance to add a systematic slide review before treating ROC. The place of node dissection in these tumors with mostly a localized stage has to be better defined. Extension of the observatory to other rare gynecologic malignant tumor is planned. No significant financial relationships to disclose.
Treatment of Giant Cell Tumour of the Femoral Head and Neck
Authors: Sheo B Tibrewal
Journal: Journal of the Royal Society of Medicine (1986)

Giant cell tumours of the femoral head and neck treated at the Nuffield Orthopaedic Centre between 1970 and 1982 were reviewed to evaluate the effectiveness of primary treatment by curettage and bone grafting. All 4 cases recurred within two years, necessitating the likelihood of recurrence following curettage and bone grafting, particularly at this anatomical site, is stressed, and the possibility that hip replacement arthroplasty be considered the primary treatment of choice is discussed.
Detection of phosphoinositide-3-kinase, catalytic, and alpha polypeptide (PIK3CA) mutations in matched tissue and plasma samples from patients with metastatic breast cancer.
Authors: P. Angenendt, K. David, H. Juhl, F. Diehl
Journal: Journal of Clinical Oncology (2010)

10502 Background: The PIK3CA gene is mutated in ∼25% of breast cancer cases and has been proposed as a potential biomarker for targeted therapies. The analysis of PIK3CA mutations in tumor tissue could therefore be an important step in the treatment decisions process. In cases where tumor tissue is not available, the detection of PIK3CA mutations in circulating plasma DNA might provide a noninvasive alternative. In order to determine the feasibility of plasma-based mutation testing, we analyzed the PIK3CA mutation status in matched tissue and plasma samples from patients with metastatic breast cancer. Methods: We used a highly sensitive and quantitative digital PCR-based approach, named BEAMing, to detect and quantify the four most common PIK3CA mutations (E542K, E545K, H1047R, H1047L) in exon 9 and 20, representing ∼87% of all reported PIK3CA mutations. We included 50 cases with metastatic breast cancer (stage IV) and assessed the mutational status of DNA extracted from FFPE tissue of the primary tumor and matched plasma. Results: PIK3CA mutations were detected in 15 out of 50 tissue sections (30%). The fraction of mutant to wild-type DNA molecules (mutational load) in the tissue samples ranged from 3.9% to 44%, with a median fraction of 15%. Identical mutations could be detected in all matched plasma samples. Mutational load in the plasma samples ranged from 0.061% to 22% in the 15 PIK3CA mutant plasma samples (median: 6.6%), representing 2 to 9,906 mutant molecules per ml plasma (median: 370 molecules). None of the patients with a PIK3CA negative tumor tissue section revealed PIK3CA mutations in the plasma DNA resulting in a 100% concordance between tissue and plasma samples. Conclusions: The detection of PIK3CA mutations in plasma DNA by BEAMing can be used as an alternative approach to tissue analysis in metastatic breast cancer patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Indivumed, Inostics Indivumed, Inostics
Effect of the Chinese herbal extract on androgen-insensitive prostate cancer cell lines in vitro and in mice
Authors: J. M. Guo, G. Du, Y. J. Liu, W. Jiang, Z. W. Zhang, G. M. Wang, Y. K. Zhang, H. L. Chen
Journal: Journal of Clinical Oncology (2005)

4741 Background: An herbal combination PC-SPES was available in US for prostate cancer treatment and withdrawn in 2002 due to contamination. In China, the number of Prostate cancer recurrence after surgical castration has increased recently. There is an urgent need to find an effective therapy for these patients. We therefore investigated the effect of the seven Chinese herbal extract in PC- SPES on androgen insensitive prostate cancer (AIPC) cell lines and in nude mice inoculated with the cancer cells. Methods: LC-MS was used to detect any synthetic drug contamination. Flow cytometry was used to measure cell cycle and apoptosis. Western blot was used to measure p16, p-RB, p21, Bax, Bad, bcl-2 and Bcl-X, Caspase and PARP protein expressions. IL-6 was detected by the method of ELISA. Each group of 40 nude mice was inoculated with PC-3 and DU-145 separately. Oral administration of the herbal extract continued for 8 weeks. After sacrifice, various tissues were examined for pathological toxicity and the tumors were studied for molecular targets. Results: The extract, found free of drug contamination, prolonged G1 and G2/M phase in PC-3 and DU-145 respectively, and induced apoptosis in both cell lines. At concentrations of 125, 250, 500 mg/kg/d, the extract inhibited the tumor growth by 27.6%, 44.15%, 53.2% in PC-3 (p<0.05) and 29.8%, 44.2%, 66.2% in DU-145 (p<0.05) when compared to the control group (N=10 each). No toxicity was found in all tissues including liver, heart and kidney. Furthermore, p16 was elevated and the phosphorylated RB protein was decreased in both cell lines and animal tumors. The proapoptic proteins Bad and Bax were increased while the antipropotic proteins Bcl-XL and Bcl-2 were decreased. These alterations resulted in the activation of caspase-3 (in cell lines) and PARP (in mice) and finally led to apoptosis. Lastly, IL-6 was found depleted in both animal tumors. Conclusions: Our results demonstrate the activity and mechanism of the herbal extract in suppressing AIPC both in vitro and in mice. We will further investigate its therapeutic benefit in human. No significant financial relationships to disclose.
When is it too EARLY to start bosentan in pulmonary arterial hypertension
Authors: F Magdy
Journal: Thorax (2008)

Pulmonary arterial hypertension is a debilitating progressive disease which eventually leads to right heart failure and death. Although observational studies indicate that early treatment initiation might be advantageous, previous clinical trials only looked at the use of bosentan (dual endothelin receptor antagonist) in patients with advanced symptomatic states (WHO functional class III and IV).

The EARLY trial …
Renal cystic disease and ammoniagenesis in Han
Authors: V E Torres, D K Mujwid, D M Wilson, K H Holley
Journal: Journal of the American Society of Nephrology (1994)

Cyst formation in conditions associated with increased renal ammoniagenesis (hypokalemia, distal renal tubular acidosis, renal mass reduction) and experimental links between increased ammoniagenesis and interstitial inflammation have suggested a role for ammonia in the pathogenesis of polycystic kidney disease (PKD). To explore this hypothesis, Han:SPRD rats, a PKD model that affects male more severely than female animals, have been used. Heterozygous cystic (Cy/+) and homozygous normal (+/+) male and female offspring of Cy/+ rats were divided at 3 wk of age into control groups drinking water and experimental groups drinking 300 mM NH4Cl, 300 mM KHCO3, 200 mM KHCO3, 200 mM KCl, 200 mM NaHCO3, or 200 mM NaCl. At 2 months of age, the rats were kept fasting from 8:00 p.m. to 8:00 a.m. in metabolic cages and urine samples were collected under mineral oil. The rats were then weighed and anesthetized for the collection of blood and kidneys. The administration of 300 mM NH4Cl, and to a lesser extent that of 200 mM NaCl, was accompanied by an increase in the urinary excretion of ammonia and aggravation of the renal cystic disease. On the other hand, the administration of 300 mM KHCO3, 200 mM KHCO3, or 200 mM NaHCO3 lowered the urinary excretion of ammonia and markedly reduced the severity of the cystic disease and interstitial inflammation. The administration of 300 mM KHCO3, and to a lesser extent that of 200 mM KHCO3, resulted in the precipitation of calcium phosphate in the medullary collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)
Psychiatric classifications: validity and utility
Authors: Assen Jablensky
Journal: World Psychiatry (2016)

Despite historical assumptions to the contrary, there is little evidence that the majority of recognized mental disorders are separated by natural boundaries. Diagnostic categories defined by their clinical syndromes should be regarded as 'valid' only if they have been shown to be truly discrete entities. Most diagnostic concepts in psychiatry have not been demonstrated to be valid in this sense, though many possess 'utility' by virtue of the information they convey about presenting symptoms, outcome, treatment response and, in some instances, aetiology. While researchers in genetics, neurobiology and population epidemiology are increasingly more likely to adopt a continuum/dimensional view of the variation in symptomatology, clinicians prefer to hold on to the categorical approach embodied in current classifications such as ICD-10 and DSM-5. Both points of view have plausible justification in their respective contexts, but the way forward may be in their conceptual reconciliation.
A phase I trial of 17-allylamino-geldanamycin (17AAG) in patients with advanced cancer
Authors: C. Erlichman, D. Toft, J. Reid, M. Goetz, M. Ames, S. Mandrekar, A. Ajei, A. McCollum, P. Ivy
Journal: Journal of Clinical Oncology (2004)

3030 Background: Therapy directed at the molecular chaperone HSP90 causes degradation of multiple client proteins critical in cancer cell proliferation and survival. 17AAG, a HSP90 directed agent, has demonstrated in vitro and in vivo antitumor effects in a variety of cancers. Methods: We performed a phase I trial to determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of 17AAG infused on days 1, 4, 8 and 11 of a 21 day cycle, to characterize the pharmacokinetics of 17AAG and its effect on chaperone and client proteins in peripheral blood mononuclear cells (PBMCs). An accelerated titration design was utilized. Surrogate markers were measured in PBMCs at baseline, day 1 and 4. Pharmacokinetic analysis was performed on day 1 only. Results: Twelve patients received 35 courses (median, 2) at 6 dose levels. Both patients treated at 308 mg/m2 experienced one or more of the non-hematologic DLTs: hyperglycemia, dehydration, diarrhea (with maximal supportive treatment), ALT, AST, and alkaline phosphatase. The MTD is 220 mg/m2. No tumor responses were seen, but one patient with metastatic melanoma was stable for ∼ 6 months on this treatment. 17AAG consistently increased HSP70 and HSF-1 in PBMCs 6 and 25 hours after treatment over pretreatment levels (p < 0.01). A newly identified client protein, Integrin-linked Kinase (ILK) was decreased significantly (p < 0.01) at 6 hours but not 25 hours after start of treatment on day 1 when compared to pretreatment levels. At the MTD the t1/2 and CLp were 2.9 ± 0.8 h and 18.5 ± 5.6 L/h/m2, respectively. The t1/2was 4.9 ± 1.1 hour for the active metabolite 17AG. Conclusions: The MTD of twice weekly 17AAG is 220 mg/m2. 17AAG induced HSP70 and HSF-1 while decreasing the client protein ILK in PBMCs. These results indicate that 17AAG is tolerable on a twice-weekly schedule and that at the MTD the drug affects the target in normal tissue. Patients are being accrued to assess the effects on tumor tissue. (Supported in part by CA15083, CA69912, CA90390, and M01-RR00585) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Kosan
SWOG S0202: A phase II trial of gemcitabine and capecitabine in patients (pts) with unresectable or metastatic gallbladder cancer or cholangiocarcinoma
Authors: S. Iqbal, S. McCoy, H. J. Lenz, S. E. Rivkin, J. N. Atkins, C. D. Blanke
Journal: Journal of Clinical Oncology (2006)

4134 Background: Pts with gallbladder cancer or cholangiocarcinoma usually present with advanced disease and limited treatment options. Based on data demonstrating effectiveness of gemcitabine in pancreatic carcinoma and the common embryologic origin of the exocrine pancreas and gallbladder, this trial was pursued. The primary objective of this study was to assess the response rate (confirmed complete and partial responses). Secondary objectives included overall survival and toxicities for gemcitabine and capecitabine. Methods: A two-stage design was used to detect a difference in the null hypothesis of 5% response probability and the alternative 20% response probability. If at least one response occurred after the first 20 pts, another 20 were to be accrued. The combination of gemcitabine 1,000 mg/m 2 IV over 100 minutes days 1, 8 and capecitabine 650 mg/m 2 BID PO days 1–14, was administered every 21 days. Results: The study accrued 57 pts from September 2003 until April 2005. Three patients were ineligible, and two others received no treatment. Characteristics of analyzable pts: 35 (73%) cholangiocarcinoma, 17 (32%) gallbladder cancer; PS 0 (18 pts), 1 (26 pts), 2 (8 pts); 26 (50%) male; median age 58.8 years (29.5–85.6). Among 51 pts evaluated for toxicity, 6 experienced grade 4 toxicities: 1 thrombosis/embolism and muscle pain, 1 fatigue and 4 neutropenia, one of whom also had grade 4 leukopenia and grade 4 anemia. Among 52 pts, there were 5 confirmed partial responses for a confirmed response probability of 10% (95% CI 3% to 21%). Four pts had an unconfirmed partial response for an overall response probability of 18% (95% CI 8% to 30%). Fourteen patients (27%) stable disease. The 6 month overall survival was 56% (95% CI 42%–70%) and median survival was 7.0 months. Conclusions: Gemcitabine and capecitabine is a well tolerated regimen with activity in pts with advanced gallbladder cancer and cholangiocarcinoma. Correlative analyses are ongoing. [Table: see text]
Maximum tolerated doses of preparations from different manufacturers.
Authors: S A Sherwin
Journal: Journal of Clinical Oncology (1987)

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.1987.5.11.1852 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3119788 Maximum tolerated doses of preparations from different manufacturers. S A SherwinxS A SherwinSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.11.1852 PDF "Maximum tolerated doses of preparations from different manufacturers.." Journal of Clinical Oncology, 5(11), pp. 1852–1853© 1987 by American Society of Clinical Oncology