tbuckley/cabot-search huggingface dataset:
The role of serum HER2 as an alternative to fluorescence in situ hybridization for HER2 in metastatic breast cancer
Authors: S.-Y. Kong, Y. Kwon, D. H. Lee, J. S. Lee, E. S. Lee, J. Ro
Journal: Journal of Clinical Oncology (2005)

681 Background: Measuring HER2 is required for the selection of metastatic breast cancer (MBC) patients for trastuzumab therapy. Since the guideline was widely accepted that recommended initial testing of tissue samples by immunohistochemistry (IHC), acceptance of 0/1+ as negative, 3+ as positive and further testing by fluorescent in situ hybridization (FISH) just in 2+ IHC, FISH study is particulary important in IHC 2+ cases to predict therapeutic response of trastuzumab therapy. Recently serum HER2 has been studied to be a complement to IHC or FISH, however, the association between serum HER2 level and HER2 gene amplification was not fully known. This study aimed to evaluate the relationship between serum HER2 level and FISH for HER2 to know whether serum HER2 can be used as an alternative to FISH for HER2 in HER2 overexpressing MBC. Methods: The HER2 overexpression was determined by IHC using polyclonal rabbit anti-human c-erbB-2 oncoprotein (Code A0485; DAKO Corp, CA, USA), and FISH analysis was performed using the PathVysion HER-2 DNA Probe Kit (Vysis, Downers Grove, IL, USA) on tissue from 126 MBC patients between Feb 2002 and Nov 2004. Serum HER2 was measured by immunoassay using Bayer ADVIA Centaur. Statistical analysis was performed using Mann-Whitney test and optimal serum HER2 values for differentiation between FISH+ (amplification) and FISH- (non-amplification) determined by receiver operating characteristics curve (ROC) analysis. Results: A total of 126 patients with HER2 overexpressing MBC with median age of 51 years included. IHC was 2+ and 3+ in 65 (52%) and 61 (48%) tumors, respectively and HER2 amplification by FISH was observed in 28% of IHC 2+ (16/58) and 100% of IHC3+ tumors (2/2). Serum HER2 levels showed significant difference at 30.6 ± 76.90 and 639.6 ± 1797.5 μg/L (mean ± SD, P = 0.01) in FISH- vs. FISH+ groups, but it was not significantly different in IHC 2+ vs. IHC 3+ groups (P = 0.54). ROC analysis showed 95% specificity at 100 μg/L with 78% positive predictive value. Conclusions: Serum HER2 may be a useful marker to predict HER2 gene amplification specifically in HER2 2+ by IHC with optimal value at 100 μg/L with 95% specificity and 78% positive predictive value. No significant financial relationships to disclose.
Histoproliferative Effect of Rauscher Leukemia Virus on Lymphatic Tissue. IV. Lactic Dehydrogenase Virus and Erythropoletin Potentiation of the Eythroid Response2
Authors: M. J. Snodgrass, J. M. Yuhas, M. G. Hanna
Journal: JNCI Journal of the National Cancer Institute (1973)

Lactic dehydrogenase virus (LDV) and erythropoietin potentiate erythroid hyperplasia stimulated by Rauscher leukemia virus (RLV) in the red pulp of the spleens of BALB/c mice. Studies of the incorporation of 59Fe into the peripheral blood erythrocytes indicated that this stimulation was probably chronic with LDV and an early acute response with erythropoietin. Both stimulants in combination with RLV induced about a 60% greater splenomegaly at 25 days than RLV alone when they were injected 1 hour before the leukemia virus. Histologically, the splenomegaly appeared to be a consequence of enhanced erythroid hyperplasia associated with the RLV infection. C-type virus particles were found, ultrastructurally, budding from erythroblasts at various stages of their development in the splenic red pulp and from reticulocytes in the peripheral blood. Erythroblasts were infected by the leukemia virus at both early and late stages of development, but apparently some cells continued to differentiate at least to the enucleated cell stage. Thus the stimulation of erythropoiesis in the splenic red pulp by LDV provides another basis for the synergistic interaction of LDV and RLV, and continued differentiation of the RNA tumor virus-infected cells of the erythrocytic series supports the contention that all cells of this compartment do not undergo a true malignant transformation during the RLV-induced splenomegaly.
There's Something Wrong with my MAM; the ER–Mitochondria Axis and Neurodegenerative Diseases
Authors: Sebastien Paillusson, Radu Stoica, Patricia Gomez-Suaga, Dawn H.W. Lau, Sarah Mueller, Tanya Miller, Christopher C.J. Miller
Journal: Trends in Neurosciences (2016)

TrendsMitochondria and the ER form close physical contacts.ER–mitochondria contacts regulate functions damaged in neurodegenerative diseases.ER–mitochondria contacts are damaged in neurodegenerative diseases.AbstractAlzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) are major neurodegenerative diseases for which there are no cures. All are characterised by damage to several seemingly disparate cellular processes. The broad nature of this damage makes understanding pathogenic mechanisms and devising new treatments difficult. Can the different damaged functions be linked together in a common disease pathway and which damaged function should be targeted for therapy? Many functions damaged in neurodegenerative diseases are regulated by communications that mitochondria make with a specialised region of the endoplasmic reticulum (ER; mitochondria-associated ER membranes or 'MAM'). Moreover, several recent studies have shown that disturbances to ER–mitochondria contacts occur in neurodegenerative diseases. Here, we review these findings.
A novel denaturing high-performance liquid chromatography (D-HPLC) based method for kit mutation screening of patients (pts) with systemic mastocytosis (SM)
Authors: S. Colarossi, S. Soverini, A. Gnani, M. Rondoni, S. Gatto, S. Merante, R. Zanotti, G. Martinelli, M. Baccarani, M. Tiribelli
Journal: Journal of Clinical Oncology (2007)

7085 Background: SM is characterized by activating mutations of Kit tyrosine kinase. While the enzimatic site (ES) type mutation D816V renders Kit resistant to imatinib, regulatory type mutations are sensitive to inhibition. Kit mutations screening with sensitive methods is important for an appropriate therapeutic management of SM. Methods: Our aims were: to set up and optimize a D-HPLC-based screening method for mutations in critical regions of Kit; to assess the sensitivity and reliability of our D-HPLC assay as compared to RFLP analysis; to characterize additional mutations. The analysis was performed on 51 SM pts. Results: For each sample, a RT-PCR product spanning the catalytic and activation loops (ES) was screened in parallel by D-HPLC, followed by sequencing of D-HPLC-positive cases, and by RFLP according to an reported method for the D816V detection. By RFLP analysis, 34/51 pts were positive for the D816V. By D- HPLC analysis, an abnormal eluition profile was seen in 36/51 pts - all the 34 RFLP-positive cases as well as two additional pts. Direct sequencing confirmed the presence of the D816V in all the 34 RFLP-positive cases and showed that in two of these cases a I798I polymorphism was also present. The two pts scored positive by D-HPLC but negative by RFLP were found to have the I798I polymorphism. The 15 pts who did not harbour ES type mutations were further investigated by D-HPLC analysis of a RT-PCR product spanning the transmembrane (TM) and juxtamembrane (JM) domains. D-HPLC showed an abnormal elution profile in 5 pts. By direct sequencing one patient showed the K546K mutation and 4 pts showed the M541L polymorphism. Conclusions: Our D-HPLC-based assay proved a straightforward, reliable and sensitive method for Kit mutation analysis and highlighted the importance of screening for mutations other than the D816V. No significant financial relationships to disclose.
Induction chemotherapy followed by surgical resection for young patients with squamous sell carcinoma of the oral tongue (SCC/T)
Authors: M. S. Kies, E. Sturgis, A. Sabichi, G. Blumenschein, B. Glisson, A. S. Garden, B. Burke, J. S. Lewin, D. Barringer, A. K. El-Naggar
Journal: Journal of Clinical Oncology (2005)

5515 Background: We have conducted a phase II trial of induction chemotherapy (CT) consisting of 3 treatment cycles with paclitaxel 175 mg/m2 day 1; ifosfamide 1000 mg/m2 IV daily x 3; and carboplatin auc 6 day 1 (TIC) followed by partial glossectomy and neck dissection in young patients (pts) with SCC/T. Objectives were: 1) to determine the activity level of TIC and the efficacy of CT followed by surgery; 2) to obtain quality of life (QoL) and swallowing functional data; and 3) to assess the association of biomarkers and tumor response. Methods: Following CT, pts underwent surgery. Postoperative radiotherapy (RT) was administered for positive surgical margins or pN2b disease. Eligible patients had age ≤ 49 yrs, performance status 0/1, no previous treatment, and staging T2/3 N0 or T1–3 N1–3, M0. Baseline oral swabs and tumor biopsies were obtained for correlative scientific studies. Surrogate markers for apoptotic (Bc1–2) and proliferation (Ki-67, p53, cylin D1) pathways were performed. Results: With median follow-up 12 months, 21 patients (12f, 9m) have been registered. Age range is 22–44 years, and median 39. Eleven (52%) were non-smokers. The staging distribution is as follows: T2N0–4; T3N0–6; TXN1–1; T2N1–1; T3N1–1; T2N2b-5; T3N2b/c-3. By RECIST, 12 of 18 (67%) evaluable pts achieved a clinical/radiographic response (10PR, 2CR). Drug tolerance was acceptable, with 11 (52%) patients having grade 3 marrow toxicity, and no patients with neutropenic fever or lethal adverse effects. There has been progressive disease in 8 pts (4 local, 5 distant), and 4 deaths. All disease-free pts surviving > 1 yr (7) returned to complete oral nutrition and demonstrated > 90% speech intelligibility. Conclusions: TIC has only moderate activity in SCC/T. Sequential treatment with CT followed by surgical resection +/- RT is feasible. For patients with tumor control, functional status is preserved. An analysis of surrogate biomarkers and correlation with prior tobacco use, tumor response to CT and disease free survival will be presented. No significant financial relationships to disclose.
A phase II, single-arm, open-label study of pralatrexate in patients with aggressive relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL): Study PDX-015.
Authors: J. E. Chang, P. J. Rosen, C. S. Magid Diefenbach, H. Kacprowicz, O. O'Connor
Journal: Journal of Clinical Oncology (2010)

e18568 Background: Pralatrexate, a targeted antifolate approved for the treatment of recurrent/refractory peripheral T-cell lymphoma, has demonstrated activity in B-cell lymphomas in preclinical models and early clinical trials. Complete tumor regression was observed in pralatrexate-treated mice bearing diffuse large B-cell lymphoma and follicular B-cell xenografts. Partial responses have been observed in patients with B-cell lymphoma in a completed phase I-II study of single-agent pralatrexate and in an ongoing phase I-II study of pralatrexate + gemcitabine. Based on this encouraging research, a phase II trial of PDX-015 has been designed to evaluate pralatrexate in relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) with a primary objective of efficacy. Methods: Patient eligibility includes: (a) histologically/cytologically confirmed, measurable, aggressive B-cell NHL, using the Revised European American Lymphoma World Health Organization disease classification; (b) progressive or persistent disease after at least 1 prior treatment; (c) Eastern Cooperative Oncology Group Performance Status ≤ 2; (d) adequate hematological, hepatic, and renal function; and (e) ≥18 years of age. Pralatrexate is administered with vitamin supplementation at an initial dose of 30 mg/m2/week for 3 weeks in a 4- week cycle. Vitamin supplementation consists of folic acid 1 mg orally daily and vitamin B12 1 mg intramuscularly every 8 to 10 weeks. This study is a 2-stage design, in which ≥1 of the first 13 evaluable patients must respond for a total of 27 evaluable patients to be enrolled. The primary end point is objective response rate per International Workshop Criteria. Secondary objectives include safety, tolerability, and pharmacokinetic profile of pralatrexate in this patient population. Enrollment is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Allos Therapeutics Allos Therapeutics Allos Therapeutics
Combination of 5-azacytidine (5-AZA) and valproic acid (VPA) in advanced solid cancers: A phase I study
Authors: A. O. Soriano, F. Braiteh, G. Garcia-Manero, L. H. Camacho, D. Hong, S. Moulder, C. Ng, R. Kurzrock
Journal: Journal of Clinical Oncology (2007)

3547 Background: 5-AZA is a DNA hypomethylating agent. VPA is a histone deacetylase inhibitor (HDACI). The combination of hypomethylating agents and HDACI has synergistic anticancer activity in vitro and in vivo. Based on this, we conducted a phase I study of the combination of 5-AZA and VPA in patients with advanced solid cancers. Methods: 5-AZA was administered SQ daily for 10 days. VPA was given orally daily titrated to 75–100 mcg/ml. Cycles were 28 days long. 5-AZA was started at 20 mg/m 2 and escalated using an adaptive algorithm based on toxicity in the prior cohort. Each cohort included 6 patients (pts). Global DNA methylation was estimated with the LINE pyrosequencing assay in peripheral blood mononuclear cells on days 1 and 10 of each cycle. Histone H3 and H4 acetylation was assessed with western blots. Results: Forty seven patients were evaluable. Median age was 60 years (15–77). 5- AZA dose levels included 20, 25, 37.5, 47, 59, 75 and 94 mg/m 2 . One DLT occurred at 37.5 (Neutropenic fever (NF)). At 75 mg/m 2 , 1 grade 3 NF and at 94 mg/m 2 , 3 DLTs (2 NF and 1 thrombocytopenia) were observed. The MTD was 75 mg/m 2 SQ daily for 10 days. Other toxicities included drowsiness (N=6), tremor (N=6), hypomagnesemia (N=1), anemia (N=2) and vomiting (N=1). Stable disease (SD) was observed in 16 pts (34%). One pt with rapidly progressive renal cell carcinoma had SD for 6 months (mos). Two pts with leiomyosarcoma of the uterus had SD for 8 and 6 mos. One pt with melanoma and two pts with uveal melanoma had SD for 4 mos. One pt with sinus adenoid cystic carcinoma and 1 with thymic carcinoma had SD for 4 mos. SD was also observed in pts with colon (N=3), sarcoma (N=2), papillary thyroid (N=2) and breast cancer (N=1). Global DNA hypomethylation was demonstrated in all of the doses of 5- AZA. Median LINE methylation pretreatment was 65% (59–70%), it declined to 61% (53–63%) by day 10 (p=0.001) and returned to baseline by day 0 of the next cycle. Histone acetylation was observed in 53% of the pts. Conclusions: The combination of 5-AZA and VPA in patients with advanced solid tumors is safe. The MTD of 5-AZA in combination with VPA was 75 mg/m 2 SQ daily for 10 days. DLTs were neutropenic fever and thrombocytopenia. Clinical benefit (SD) was observed in 16 pts (34%). Transient global hypomethylation and histone acetylation were demonstrated. No significant financial relationships to disclose.
Abstract 15268: Role of Transient Receptor Potential Vanilloid 4 Channels in the Periventricular Nucleus (PVN) Neurons on the Regulation of Blood Pressure in Dahl R versus Dahl S Rats
Authors: Lirong Guo, Tiecheng Zhong, Stephen T O'Rourke, Chengwen Sun
Journal: Circulation (2013)

Transient receptor potential vanilloid 4 (TRPV4) channels are expressed in brain neurons involved in systemic osmoregulation; and intravenous administration of TRPV4 channel antagonists elevates ar...
A Population-Based Analysis of Application of WHO Nomenclature in Pathology Reports of Pulmonary Neuroendocrine Tumors
Authors: Jules L. Derks, Robert Jan van Suylen, Erik Thunnissen, Michael A. den Bakker, Egbert F. Smit, Harry J.M. Groen, Ernst J.M. Speel, Anne-Marie C. Dingemans
Journal: Journal of Thoracic Oncology (2016)
Horizontal Gene Transfer from Bacteria Has Enabled the Plant-Parasitic Nematode<i>Globodera pallida</i>to Feed on Host-Derived Sucrose
Authors: Etienne G.J. Danchin, Elena A. Guzeeva, Sophie Mantelin, Adokiye Berepiki, John T. Jones
Journal: Molecular Biology and Evolution (2016)

The evolution of plant-parasitic nematodes (PPN) is unusual in that these organisms have acquired a range of genes from bacteria via horizontal gene transfer (HGT). The proteins encoded by most of these genes are involved in metabolism of various components of the plant cell wall during invasion of the host. Recent genome sequencing projects for PPN have shown that Glycosyl Hydrolase Family 32 (GH32) sequences are present in several PPN species. These sequences are absent from almost all other animals. Here, we show that the GH32 sequences from an economically important cyst nematode species, Globodera pallida are functional invertases, are expressed during feeding and are restricted in expression to the nematode digestive system. These data are consistent with a role in metabolizing host-derived sucrose. In addition, a detailed phylogenetic analysis shows that the GH32 sequences from PPN and those present in some insect species have distinct bacterial origins and do not therefore derive from a gene present in the last common ancestor of ecdysozoan species. HGT has therefore played at least two critical roles in the evolution of PPN, enabling both invasion of the host and feeding on the main translocation carbohydrate of the plant.
The role of surgery in the management of selected patients with small-cell carcinoma of the lung.
Authors: R R Baker, D S Ettinger, J D Ruckdeschel, J C Eggleston, M F McKneally, M D Abeloff, J Woll, D J Adelstein
Journal: Journal of Clinical Oncology (1987)

This study was designed to evaluate the efficacy of surgical resection of the primary tumor and lymph nodes in patients with localized small-cell carcinoma who had responded to induction chemotherapy. The study was performed in 37 patients who received two cycles of chemotherapy consisting of cyclophosphamide, doxorubicin, and etoposide. Those patients who achieved a complete or partial (greater than 50%) response were evaluated for thoracotomy and the primary tumor and regional lymph nodes excised when feasible. Postoperatively, the patients received prophylactic cranial irradiation and were maintained on the same chemotherapy for an average of 11 months. Twelve patients were resected and found to have residual small-cell carcinoma in the operative specimen (ten) or no residual disease (two). Seven of these patients (58%) are alive without evidence of disease (median follow-up, 24 months). Seven other patients who were resected proved to have either residual foci or small-cell carcinoma mixed with adenocarcinoma or large-cell carcinoma (four) or only focal areas of adenocarcinoma, large-cell carcinoma, or squamous-cell carcinoma with no evidence of residual small-cell carcinoma. Five of these patients (71%) are alive without evidence of disease (median follow-up, 36 months). Two of the 16 patients who were not resected but treated with chemotherapy and radiation are alive at 15 and 31 months without evidence of disease, the other 14 are dead of disease.
Lipoplatin monotherapy: A phase II trial in second line treatment of metastatic non-small cell lung cancer
Authors: A. Ravaioli, M. Papi, E. Pasquini, M. Marangolo, B. Rudnas, M. Fantini, S. V. Nicoletti, F. Drudi, C. Possenti, E. Tamburini, L. Gianni
Journal: Journal of Clinical Oncology (2007)

18160 Background: Lipoplatin is a liposome encapsulated form of cisplatin. Phase I studies on lipoplatin showed an excellent toxicity profile of the compound. Therefore we performed a phase II trial in pre-treated patients with advanced non-small cell lung cancer (NSCLC). Methods: Nineteen patients with stage IV NSCLC pre-treated with first line chemotherapy were enrolled in our study. Patient selection criteria included: histologically confirmed malignancy type or cytological confirmation of advanced NSCLC, at least one measurable bi-dimensional lesion outside an irradiation field, stage IV disease, a life expectancy of more than 3 months, previous chemotherapy regimens, PS 0–2, age between 18 and 75, good bone marrow function (peripheral absolute granulocyte count of &gt; 2,000/mm3 and platelet count of 100,000/mm3) and liver function (bilirubine less or equal to 1,5 mg/dl). Patients with symptomatic brain metastases or other severe illnesses were excluded from the study. Written informed consent was required from each patient prior to inclusion. The protocol was approved by the Local Ethical Commitee. We administered lipoplatin at the dose of 100 mg/m 2 every fourteen days as second line chemotherapy. Primary endpoint was response rate. Results: We enrolled 19 patients, median age 64, with stage IV NSCLC. This was an open label single-arm trial. Statistical analysis was performed with the SPSS statistical program (version 11.0). Survival curves were estimated by the Kaplan-Meier method. All of the patients completed at least 6 cycles and were evaluated for response and toxicity. After 19 patients were treated we obtained only one partial response (5.2%) and three stable diseases (15.9%) and the study was stopped. Median time to progression was four months and median survival time was 7 months. Conclusions: In this study lipoplatin as second line drug demonstrated a lower activity in comparison to other drugs used in second line treatment. Nevertheless at the light of the excellent safety profile shown we think that the possibility to increase the dose in a new phase I-II study with escalation of the dosage should be considered. No significant financial relationships to disclose.