tbuckley/cabot-search huggingface dataset:
Humanized anti-CEACAM6 PEGylated scFv: A promising novel therapy for pancreatic cancer
Authors: D. Mahadevan, H. Garewal, C. Riley, Y. Zhu, K. Engelhardt, L. Cooke, R. Nagle, J. Saldanha, D. Von Hoff
Journal: Journal of Clinical Oncology (2007)

3042 Background: Novel Therapies for pancreatic cancer (PC) based on biological insight are urgently needed. CEACAM6, a member of the carcinoembryonic antigen (CEA) family, is a cell surface oncogene on PC cells. It is a glycoprotein composed of 3 Ig-like domains (Mr ∼35.2kD) and is linked to the plasma membrane via a glycophospholipid linked anchor. It is over-expressed on ≥95% PC patients’ found irrespective of stage of disease and represents a target for antibody therapy. Methods: Murine anti-CEACAM6 monoclonal antibody (Mab) 13–1 was humanized by a structure-based approach and single chain variable fragments (scFv) designed consisting of a Gly/Ser-linker which includes a cysteine residue for PEGylation. Murine scFv and 4 humanized scFv fragments (Version.1, 2, 7, 8) were bacterially expressed, purified, PEGylated and evaluated for activity alone or in combination with gemcitabine in human PC cell lines and mouse xenograft tumors. Cell viability, apoptosis and in-cell Westerns were done for efficacy and binding. Mouse xenograft tumors were treated with scFv or PEGylated scFv or combination with gemcitabine. Tumors (treated Vs untreated) were analyzed by immunohistochemistry for Ki-67, CD31, CEACAM6 and Caspase 3 Results: Mab 13–1, murine and 4 humanized scFvs’ were cytotoxic to CEACAM6 expressing PC cells (BxPC-3, HPAF-2) and not to PC cells that lack CEACAM6 (CaPan-2) with increased PARP-cleavage that was dose dependent (IC 50 =10μg/mL). Western blotting of culture media and serum from xenograft mice showed that CEACAM6 is not shed. In-cell Western confirmed humanized V.7 to be the best binder (K D =1–10μg/mL) confirming protein-protein interaction studies performed in silico with homology models of murine and humanized scFvs’ and CEACAM6. The murine scFv alone or the humanized scFV (V.8) in combination with gemcitabine delayed tumor growth by &gt;50%. This tumor reduction correlated well with the immunohistochemical markers of response. Conclusions: We have demonstrated that CEACAM6 is a clinically relevant target in PC and that a PEGylated humanized scFv is a novel effective therapy alone and/or in combination with gemcitabine. Humanized scFv V.7 is undergoing mouse xenograft evaluation and expect will be the most effective agent to take forward into clinical development. No significant financial relationships to disclose.
Preliminary safety and effectiveness of bevacizumab (BV) based treatment in subpopulations of patients (pts) with non-small cell lung cancer (NSCLC) from the ARIES study: A bevacizumab (BV) treatment observational cohort study (OCS)
Authors: N. A. Fischbach, D. Spigel, J. Brahmer, J. Garst, R. Robles, C. Chung, L. Wang, A. Sing, T. Lynch
Journal: Journal of Clinical Oncology (2009)

8040 Background: Phase III trials have shown that bevacizumab (Avastin, BV), an anti-VEGF monoclonal antibody, prolongs progression-free and overall survival in advanced NSCLC pts. To further define clinical outcomes associated with BV treatment among a broader population of NSCLC pts in a real-world setting, the ARIES OCS was initiated. Pt populations in OCSs are often more reflective of pts encountered in practice, permitting examination of treatment benefit and toxicity in subgroups that might be too small for study in traditional randomized controlled trials (RCTs). The NSCLC cohort in ARIES will assess clinical outcomes in the overall cohort as well as subpopulations such as the elderly, pts with poor PS or pts on concurrent anticoagulants (AC). Methods: Pts with advanced NSCLC whose 1 st -line therapy includes BV may enroll. 257 sites are enrolling pts; total accrual of 2000 pts is expected. There are no protocol-specified treatments or assessments. Data is collected at baseline (BL) then quarterly, including targeted adverse events (AEs) and BV-related serious AEs. Clinical outcomes will be descriptively summarized by baseline characteristics. Multivariate analyses will be conducted if cohort size is sufficient. Results: As of 9/15/08, 1518 NSCLC pts have enrolled. Median F/U is 7.5 mos. Key BL characteristics: 20% ≥75 yrs; 67% adenocarcinoma; 10% ECOG ≥2; 8% brain metastasis; 5% therapeutic AC. The most common 1 st -line chemotherapy regimen was carboplatin/paclitaxel (64%). Key safety outcomes and cohort size of subpopulations are in the Table . Conclusions: The safety of BV in subpopulations of pts in ARIES (elderly pts, pts with ECOG PS ≥2, with brain mets at BL, or on therapeutic AC) is generally consistent with safety results from RCTs. Updated outcomes analyses will be presented at the meeting for &gt;1600 pts and subpopulations. [Table: see text] [Table: see text]
Evidence for independent acquisition of group I introns in green algae.
Authors: M J Van Oppen, J L Olsen, W T Stam
Journal: Molecular Biology and Evolution (1993)

We report the occurrence of a group I intron, 452 nucleotides in length, in the nuclear small-subunit ribosomal gene of the benthic seaweed Urospora penicilliformis, a member of the green algal class Ulvophyceae. Group I introns have been reported in fungi, myxomycetes, the ciliate genus Tetrahymena, and recently in five unicellular chlorophycean algae. The sequence of the conserved core of the U. penicilliformis group I intron was aligned with that of 15 other introns of this type, and the evolutionary relationships among these introns were examined. Comparison of the "intron" tree with phylogenetic hypotheses of the intron-harboring organisms shows that nuclear group I introns in green algae have arisen several times and are not lineage specific.
Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy.
Authors: I Tepler, S A Cannistra, E Frei, R Gonin, K C Anderson, G Demetri, J Niloff, H Goodman, H Muntz, M Muto
Journal: Journal of Clinical Oncology (1993)

Attempts to increase dose-intensity in clinical practice have been limited by cumulative hematologic toxicity despite the use of hematopoietic growth factors. To address this problem, we designed a study to determine whether four cycles of dose-intensive chemotherapy with carboplatin could be administered in the outpatient setting using granulocyte-macrophage colony-stimulating factor (GM-CSF) and peripheral-blood progenitor cells (PBPCs) that had been harvested before initiation of treatment.An initial cycle (cycle no. 0) of cyclophosphamide 4 g/m2 followed by GM-CSF was used to mobilize PBPCs harvested by leukapheresis for 6 consecutive days. Cycles no. 1 through 4 consisted of outpatient carboplatin 600 mg/m2 and cyclophosphamide 600 mg/m2 followed by GM-CSF 5 micrograms/kg subcutaneously (SC) twice per day every 28 days. In cycle no. 1, PBPC were not reinfused to assess the effects of GM-CSF alone. In cycles no. 2 through 4, PBPCs were reinfused on day 3 in an outpatient setting.In eight assessable patients, the addition of PBPCs in cycle no. 2 resulted in a significant reduction in the median duration of thrombocytopenia less than 20,000/microL (6.5 v 1 day; P = .016), days to platelets more than 50,000/microL (20.5 v 15 days; P = .020), number of platelet transfusions (five v 1.5; P = .016), and duration of neutropenia (absolute neutrophil count [ANC] < 1,000/microL (7 v 2.5 days; P = .008) when compared with cycle no. 1. Dose-limiting hematologic toxicity, defined as more than 7 days of platelets less than 20,000/microL or ANC less than 500/microL, was observed in four of eight patients during cycle no. 1, but not during cycles no. 2, 3, and 4 of chemotherapy supported by PBPCs (a total of 19 cycles in eight patients). Five of eight patients completed all four cycles of high-dose therapy. Three patients did not complete four cycles due to late thrombocytopenia (n = 2) or tumor progression (n = 1).These results indicate a benefit of PBPCs in addition to GM-CSF in alleviating myelosuppression of dose-intensive chemotherapy. Initial collection of PBPCs may allow administration of repetitive cycles of high-dose chemotherapy with acceptable toxicity to outpatients at disease onset.
Assessment of operability by means of CTPA and perfusion SPECT in patients with chronic thromboembolic pulmonary hypertension
Authors: Aleksandar Grgic, Florian Miodek, Christian Frantz, Arno Buecker, Fadi Khreish, Michael Boehm, Hans-Joachim Schaefers, Robert Bals, Carl-Martin Kirsch, Heinrike Wilkens
Journal: European Respiratory Journal (2011)

Objective:  Chronic thromboembolic pulmonary hypertension (CTEPH) is curable with pulmonary endarterectomy (PEA). The criteria for identification of PEA-amenable patients need to be standardized.The aim of this study was to evaluate the value of rigidly registered CT pulmonary angiography (CTPA) and perfusion SPECT in differentiating between operable and non-operable patients.   Methods:  49 patients with CTEPH (21 men, 58±13 years) were evaluated for PEA by interdisciplinary board using available diagnostic information and served as the gold standard.SPECT was evaluated by a lobe based visually assessed perfusion score ranging from 0 [no perfusion] to 1 [normal perfusion]),after which the percentage of vascular obstruction (PVO) was calculated: PVO = [1 – Perfusion score] × 100. By CTPA, the vascular obstruction index (OI) of central, peripheral, and global PA bed and diameters of large vessels(pulmonary artery (PA), aorta (Ao) and PA/Ao) was determined. In angiography PA pressure (PAP), PA resistance (PVR) and wedge pressure (PCm) were determined. Receiver operating characteristics (ROC) analysis was performed.   Results:  Mean PAP, PVR and PCm was 48±11 mmHg, 878±461dynes sec cm -5 , and 11±5 mmHg. 30 patients were chosen as candidates for PEA. Hemodynamic values were not able to differentiate between operable and non-operable patients. PVO and central OI separated PEA-amenable patients (both p   Conclusion:  An accurate interpretation of rigidly registered CTPA and perfusion SPECT may contribute to stratification of operability in patients with CTEPH.
Functional integrity of proximal tubule cells
Authors: Y You, D J Hirsch, N S Morgunov
Journal: Journal of the American Society of Nephrology (1993)

Electrophysiologic and morphologic changes during cooling and perfusion with preservation solutions in isolated perfused proximal straight tubules from Swiss white mice were investigated. In standard Ringer-substrate solution, cooling from 37 degrees C to 22 and 4 degrees C depolarized both transepithelial potential and basolateral cell membrane potential. Basolateral k+ transference number and cell membrane conductances were also significantly reduced. An increase in intracellular Na+ activity was observed only during cooling from 37 to 4 degrees C. No cell swelling was detected when tubules were perfused with Ringer-substrate solution at all three temperatures up to 1 h. Perfusion with Euro-Collins' (EC) solution at 37 degrees C resulted in rapid cell swelling, associated with rapid deterioration of transepithelial potential. Substitution of glucose with mannitol abolished the damaging effect of EC solution at 37 degrees C. EC perfusion at 22 degrees C also led to cell swelling and deterioration of transepithelial potential, but after a 10-min delay. In comparison, perfusion with University of Wisconsin (UW) solution at 22 or 37 degrees C had no effect on cell volume. Less damage to transepithelial potential was observed after the UW perfusion. It was concluded that EC solution is more damaging than UW solution to kidney tubules at 22 and 37 degrees C. The presence of EC solution in the renal interstitium during the rewarming phase may contribute significantly to reperfusion injuries in kidney transplantation.
Abstract 10387: Performance of 18F-Fluorodeoxyglucose Positron Emission Tomography Within 14 days From Onset of Suspected Acute Myocarditis Achieved Excellent Agreement With Endomyocardial Biopsy for Detecting Active Inflammatory Left Ventricular Posterior Wall
Authors: Koya Ozawa, Nobusada Funabashi, Michiko Daimon, Hiroyuki Takaoka, Hiroyuki Takano, Masae Uehara, Yoshio Kobayashi
Journal: Circulation (2013)

Purpose:  To determine optimum periods for 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) examination in subjects with suspected acute myocarditis, we compared 18F-FDG PET with endomyocardial biopsy (EMB) using the latest definitions of 18F-FDG PET for active inflammatory left ventricular (LV) posterior wall (LVPW).   Methods:  Retrospective analysis of 29 subjects (18 male, 48 ± 18 yrs) who have symptoms or LV dysfunction underwent both 18F-FDG PET (Advance NXi) and EMB from LVPW within 3 months.   Results:  When we defined 18F-FDG PET positive inflammatory findings of LVPW as ‘diffuse’, or ‘focal on diffuse’ patterns (definition 1), sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of 18F-FDG PET for detecting active inflammatory LV posterior wall compared with EMB was 85, 50, 58, and 80%, respectively. Sensitivity, specificity, PPV and NPV of 18F-FDG PET for detecting inflammatory LVPW on EMB were all 100% when 18F-FDG PET was performed at 1-14 days after onset of suspected acute myocarditis. When we defined 18F-FDG PET positive inflammatory findings of LVPW as ‘focal on diffuse’ patterns only (definition 2), sensitivity, specificity, PPV, and NPV of 18F-FDG PET for detecting inflammatory LVPW compared with EMB were 54, 81, 70, and 68%, respectively. Sensitivity, specificity, PPV and NPV of 18F-FDG PET for detecting inflammatory LVPW on EMB were all 100% when 18F-FDG PET was performed at 1-14 days after onset of suspected acute myocarditis. Sensitivity was significantly greater in definition 1 than definition 2, but there were no significant differences in specificity, PPV and NPV between the two definitions.   Conclusions:  On both definitions, 18F-FDG PET showed excellent agreement with EMB for detecting active inflammatory LVPW in subjects with clinically suspected active acute myocarditis. If possible, 18F-FDG PET should be performed within 14 days after the onset to maintain high diagnostic accuracy compared with EMB.
Correlation between clinical response according to WHO criteria and pathological response according to Chevallier and Sataloff in inflammatory breast cancer (IBC)
Authors: J. Bonneterre, A. Mailliez, S. Giard, C. Chaveron, Y. Belkacemi, L. Vanlemmens, M. Baranzelli
Journal: Journal of Clinical Oncology (2007)

11033 Introduction: IBC has a very poor prognosis ; the first treatment is first primary chemotherapy, followed by surgery and radiotherapy. It has been shown that patients experiencing a complete pathological response haved a longer survival . The pathological response has thus to be carefully assessed. Material and Methods: The aim of this retrospective study was to determine whether there islook for a correlation between clinical response with (WHO criteria) and pathological response using Chevallier’s and Sataloff’s classifications. 56 successive patients received an anthracycline- based chemotherapy regimen for IBC before surgery; for all of these patients a pathological analysis had beenwas performed before chemotherapytreatment and after surgery. Alll the specimens werehave been reviewed by the same pathologist. Results: There is a very good correlation between the 2 pathological classifications fAmong the 56 patients, there were 3 complete clinical responses, which were also pathological complete responses according to both classifications.or the complete responders only. In all the other cases, no correlation wascould be found between the 3 classifications . It was particularly striking for all the 41 patients tumours classified grade 3 according to Chevallier who could be classified clinically (with WHO) or pathologically (with Sataloff) in either of the 4 groups from complete responseders to progressive disease . Overall , in this our series , 3 patients according to Chevallier and 11 according to Sataloff were complete pathological responders. Discussion: The lack of correlation between clinical and pathological classifications could be explained , at least in part, by the fibrosis often observed after primary chemotherapy. The differences observed between the 2 pathological classifications highlight the fact that there is no standard and that further research is neede in that perspective. [Table: see text] No significant financial relationships to disclose.
Coexpression of matrix metalloproteinase-7 (MMP7) and phosphorylated insulin growth factor receptor I (pIGF-IR) as predictors of resistance to anti-EGFR therapy in advanced colorectal cancer (ACRC): A GEMCAD study
Authors: C. Horndler, R. Gallego, V. Alonso, V. Alonso, P. Escudero, M. Jimeno, X. Garcia-Albeniz, C. Fernandez-Martos, S. Castellví-Bel, J. Maurel
Journal: Journal of Clinical Oncology (2009)

4063 Background: IGF-IR is supposed to have anti-apoptotic and mitogenic properties in colorectal cancer and by transactivation can promote EGFR phosphorylation. MMP-7 is produced by colorectal cancer cells and by degrading IGFBP-3 can activate IGF-IR. Methods: We retrospectively investigated the role of pIGF-IR immunoreactivity (IHC) (Rubini) and MMP-7 IHC in primary CRC or metastases, to predict response rate (RR), progression free survival (PFS) and overall survival (OS) in ACRC patients (pts) treated with either cetuximab or panitumumab as second or third line therapy. RAS mutational status of codons 12/13 was determined using quantitative PCR-based assay. CT scans were done every 1.5–2 months (m) until progressive disease. Results: A total of 99 pts with available tissue from 168 pts with ACRC treated with anti-EGFR therapy in 4 Spanish Institutions, were analysed for RAS mutational status, pIGF-1R and MMP-7. There were no major differences in RR (18.8 vs 16%), PFS [3.3 vs. 3.1 months (m)] and OS (7.7 vs. 7m) between the whole and selected cohort. Fifty-seven (57.6%) pts were male, the median age was 62 (range 34–79) years, the median number of previous chemotherapy lines was 2 (range 1–3) and PS was distributed as follow: PS0, 17 (17.2 %) pts; PS1, 66 (66.7%) pts and PS2, 16 (16.2%) pts. Expression of MMP-7 and pIGF-1R were observed in 48 (48.5%) and 52 (52.5%) pts respectively. Co-expression of MMP-7 and pIGF-1R [Double Positive (DP)] was observed in 26 (26.3 %) pts and in 16 (24%) out of 66 RAS wild-type (WTRAS) pts. There was no association between RAS mutational status and DP (p=0.52). DP progressed more than non-DP pts both in the overall sample (73 vs. 43%, p=0.028) and in WTRAS pts (75 vs. 32%, p=0.011). In the subset of WTRAS pts, DP pts also have a poorer OS: 6.4 (95% CI 5.8–7.1) m vs. 8.6 (95%CI 6.0–11.3) m (p=0.005), and a trend for worse PFS 2.7 vs 4.0 m (p=0.11). Conclusions: Co-expression of pIGF-1R and MMP7 is associated with resistance to anti- EGFR therapy in WTRAS pts. Our study suggests that pts with WTRAS and DP could be a target population to assay new anti-IGF-1R compounds. No significant financial relationships to disclose.
Reducing decisional conflict in men making treatment decisions on newly diagnosed localized prostate cancer.
Authors: David C. Johnson, Eric Wallen, Angela Smith, Michael Woods, Raj Pruthi, Dana Mueller, Matthew Edward Nielsen
Journal: Journal of Clinical Oncology (2015)

106 Background: Men with newly diagnosed localized prostate cancer (LPC) face a complex, preference-sensitive treatment decision. Low “decisional conflict” (DC), defined as uncertainty over treatment choice, is a key component of decision quality. Lower scores on the Decisional Conflict Scale (DCS) are associated with lower likelihood of delaying a decision and assessing blame to a physician for bad outcomes. We hypothesized that using a novel software application to measure and report patients’ preferences for LPC treatment outcomes as part of a pre-consultation intervention would improve decisional quality in men with LPC by reducing DC. Methods: Men with newly diagnosed LPC completed the online WiserCare (WiserCare, Inc) prostate cancer module prior to their initial consultation at the University of North Carolina, Chapel Hill Multi-disciplinary Urologic Oncology Clinic. WiserCare is a software application that provides education, preference assessment, and personalized decision analysis for patients. Preferences are measured using conjoint analysis. WiserCare then generates an individualized report ranking treatment options based on their “fit”(expected value) based on clinical prognostic factors and personal preferences. This report is used with their physician during counseling. We measured DCS scores before and after completion of the WiserCare module. Paired 2-tailed T-tests were to evaluate the changes in DCS scores. Results: 48 men completed the WiserCare module and DCS prior to their initial consultation for newly diagnosed LPC. Overall DCS score decreased by 38% (p&lt;0.00001) after completion of the WiserCare module. Analysis of DCS subscales revealed improvements in all five, including feeling informed by 56% (p&lt;0.00001), value clarity by 49% (p=0.001), feeling effective in decision making by 36% (p=0.0001), feeling supported by 31% (p=0.0037), and reduced uncertainty by 24% (p=0.0023). Conclusions: A pre-consultation web-based module integrating evidence-based information, individualized clinical data and personal preference data is a feasible and effective strategy to reduce decisional conflict in men making treatment choices for localized prostate cancer.
Transplantation of Homologous Erythropoietic Elements in Rats after Sublethal Doses of X Radiation
Authors: T T ODELL, B C CALDWELL
Journal: JNCI Journal of the National Cancer Institute (1958)

Transplantation of Homologous Erythropoietic Elements in Rats after Sublethal Doses of X Radiation Get access T. T. Odell, Jr., T. T. Odell, Jr. Biology Division, Oak Ridge National Laboratory,2Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar B. C. Caldwell B. C. Caldwell Biology Division, Oak Ridge National Laboratory,2Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 20, Issue 4, April 1958, Pages 851–858, https://doi.org/10.1093/jnci/20.4.851 Published: 01 April 1958 Article history Received: 02 December 1957 Published: 01 April 1958
Helicobacter pylori antibody positivity in idiopathic pulmonary fibrosis
Authors: David Bennett, Elena Bargagli, Maria Stella Campagna, Maria Pieroni, Natale Figura, Paola Rottoli
Journal: European Respiratory Journal (2013)

Helicobacter pylori (HP) is a Gram-negative, spiral-shaped bacterium linked to gastrointestinal and extra-gastrointestinal disorders including respiratory diseases. Some recent reports proposed a protective role in bronchial asthma and rhinitis.  Serological HP Antibody positivity was studied in 45 IPF (33 male, age 66.2 ±10.2 years) and 160 healthy controls (85 male, age 64.5 ±12 years). All patients were routinely followed at the Regional Center for Sarcoidosis and other Interstitial Lung Diseases of the University of Siena. Diagnosis of IPF was made according to the last ATS/ERS/JRS/ALAT guidelines. Statistically lower prevalence of HP Ab positivity was found in patients than controls (40.0% vs. 66.8%, p 0.05). The present study revealed that the positivity to HP Ab in serum of patients with IPF is lower than general population but it was associated with a more severe disease. Further investigations in a larger population are needed to confirm our results on Helicobacter pylori influence on IPF.