Development of a System to Validate Group 3 Facsimile Equipment. Phase I.

1981 ◽  
Author(s):  
Richard A. Schaphorst
Keyword(s):  
Phase I ◽  
Group 3

First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2612-2612
Author(s):  
Karen A. Autio ◽  
Celestia S. Higano ◽  
Luke T. Nordquist ◽  
Leonard Joseph Appleman ◽  
Tian Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Phase I ◽  
Dose Escalation ◽  
Checkpoint Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Therapeutic Vaccines ◽  
Castration Resistant ◽  
Viral Particles ◽  
Group 3

2612 Background: Therapeutic vaccines targeting PC-associated antigens represent attractive approaches in combination with immune checkpoint inhibitors (ICI). Safety/antitumor activity of PF-06753512 (PrCa VBIR) was evaluated in a phase I, dose-escalation and expansion study in patients (pts) with BCR prior to ADT and in pts with mCRPC either prior to or after failure of novel hormone therapy. PrCa VBIR consists of: 1) priming immunization with a replication-deficient adenoviral vector (AdC68) expressing PSA, prostate-specific membrane antigen and prostate stem cell antigen; 2) boosts with plasmid DNA (pDNA) encoding the same antigens by IM electroporation; 3) ICI given subcutaneously, including anti CTLA-4 antibody tremelimumab (TRM) and anti PD-1 antibody sasanlimab (SSL). Methods: AdC68 ± ICI(s) were given on months (mos) 1 and 5 and pDNA ± ICI(s) on mos 2–4 and 6–8. After 8 mos, maintenance pDNA + ICI(s) were given every 1 or 2 mos. In Part A (6 escalation cohorts), pts with mCRPC received AdC68 (4 or 6x10e11 viral particles) + pDNA 5 mg ± ICIs (TRM alone 80 mg; TRM 40 or 80 mg + SSL 130 or 300 mg). In Part B (3 expansion cohorts), pts with mCRPC received AdC68 6x10e11 + pDNA 5 mg + TRM 80 mg + SSL 300 mg; pts with BCR received similar vector and pDNA + TRM 80 mg ± SSL 130 mg. Primary objectives: Assess overall safety (CTCAE v4.03), determine expansion dose. Secondary objectives: Anti-tumor activity (RECIST v1.1, Prostate Cancer Working Group 3, PSA 50 response) and immune response. (Note: Database remains open, some queries pending). Results: As of Sept 15, 2020, 91 pts were treated in dose-escalation (n=38) and expansion (n=53; BCR=35, mCRPC=18). Immune responses (ELISpot) were positive in some pts. Grade (G) 3 or 4 treatment-related adverse events (TRAEs) developed in 38.5% (35/91) of pts. G5 TRAEs occurred in 2 pts (n=1 G4 myasthenia gravis + G5 pulmonary embolism; n=1 G5 myocarditis). irAEs were more frequent in BCR compared to mCRPC. See the table for efficacy data. Conclusions: Vaccination with PrCa VBIR had a manageable safety profile. TRAEs increased when 2 ICIs were given. Some pts with BCR experienced durable PSA-50 responses without ADT; patients with mCRPC had few objective tumor responses, but had prolonged median rPFS. PrCa VBIR appears to stimulate antigen-specific immunity and results in noticeable antitumor activity, particularly in androgen sensitive disease. Clinical trial information: NCT02616185. [Table: see text]

scholarly journals Phase Variation Analysis of Coxiella burnetii during Serial Passage in Cell Culture by Use of Monoclonal Antibodies

2002 ◽  
Vol 70 (8) ◽  
pp. 4747-4749 ◽  
Author(s):  
Akitoyo Hotta ◽  
Midori Kawamura ◽  
Ho To ◽  
Masako Andoh ◽  
Tsuyoshi Yamaguchi ◽  
...  
Keyword(s):  
Cell Culture ◽  
Monoclonal Antibodies ◽  
Phase I ◽  
Coxiella Burnetii ◽  
Phase Variation ◽  
Serial Passage ◽  
Variation Analysis ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

ABSTRACT Antigenic changes in Coxiella burnetii Nine Mile strain phase I during serial passages in cell culture were analyzed with three groups of monoclonal antibodies (MAbs) against lipopolysaccharide. The MAbs of group 1 did not react with organisms that were passaged over five times, and the MAbs of group 2 did not react with organisms that were passaged over eight times. The MAbs of group 3 reacted with organisms passaged up to 15 times but did not react with phase II cells. These results suggest that C. burnetii could be differentiated into four phase states during phase variation.

scholarly journals Phenotypes of Obstructive Lung Diseases in Elderly: A Real-Life Study in a Non-Clinical Setting

2020 ◽  
Author(s):  
João Gaspar-Marques ◽  
Iolanda Caires ◽  
Teresa Palmeiro ◽  
Paula Leiria Pinto ◽  
Maria-Jesus Chasqueira ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Lung Diseases ◽  
Phase Iii ◽  
Airflow Limitation ◽  
Lung Volumes ◽  
Obstructive Lung Diseases ◽  
Medical Visits ◽  
Tnf Α ◽  
Group 3

Abstract Background: This study aimed to characterize the clinical, functional, inflammatory and immunological features of the main obstructive lung diseases (OLD) in elderly. Methods: We included subjects aged ≥ 65 years. In Phase I, participants answered standardized questionnaires, performed spirometry, fractional exhaled nitric oxide, an atopy assessment and blood analysis. In Phase II, patients with COPD or asthma criteria and a control group were invited to undergo a more detailed evaluation that included the determination of IL-1-β, IL-5, IL-6, IL-13, TNF-α and periostin. In Phase III was assessed the frequency of non-scheduled medical visits due to respiratory exacerbations, hospitalization and mortality. Results: Phase I included 286 participants. The median age was 85.8 (P27-P75: 81.0 - 90.2) years and 69% were females: 27.3% had chronic obstructive pulmonary disease (COPD) without asthma (Group 1), 2.8% asthma without COPD (Group 2) and 5.2% presented asthma and COPD traits (Group 3). The remaining participants (64.7%), without asthma or COPD, were classified as Group 4. At this stage, Group 3 was more atopic and presented a lower post-bronchodilator FEV 1 and FEV 1 /FVC. In Phase II, that included 82 participants, Group 3 presented the higher median values of TNF-α (p-value: 0.072) and higher lung volumes (p=0.001). No statistically differences were found for other cytokines among groups. In Phase III, Group 3 patients needed more non-scheduled visits. Conclusions: In our study patients with asthma and COPD traits presented more severe airflow limitation, higher values of TNF-α, higher lung volumes and more non-scheduled medical visits.

scholarly journals MVA-5T4 immunotherapy and low-dose cyclophosphamide for advanced colorectal cancer (TaCTiCC): An open-label, randomized phase I/II trial.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 154-154
Author(s):  
Martin Scurr ◽  
Tom Pembroke ◽  
Richard Adams ◽  
Daniel Blount ◽  
Alison Brewster ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Immune Responses ◽  
Phase I ◽  
Low Dose ◽  
Advanced Colorectal Cancer ◽  
Induced Responses ◽  
Open Label ◽  
Group 3 ◽  
Group 1

154 Background: Current immunotherapies including checkpoint inhibitors and vaccines for advanced colorectal cancer (CRC) have been largely ineffective. We hypothesized that combining an MVA-based vaccine targeting the tumor-associated antigen 5T4 (TroVax) with low-dose cyclophosphamide to deplete Foxp3+regulatory T-cells (Tregs), could improve immunological responses and patient outcomes. Methods: In this open-label phase I/II clinical trial, TaCTiCC (TroVax and Cyclophosphamide Treatment in Colorectal Cancer) 53 patients with inoperable metastatic CRC were randomized to receive either no treatment (group 1, n=8), metronomic low-dose CPM (50mg B.D. during treatment weeks 1&3; group 2, n=9), TroVax only (6 i.m. injections weeks 4 to 16, group 3, n=18), or low-dose CPM followed by TroVax (group 4, n=18). The primary endpoint was boosted anti-5T4 responses at week 7, as measured by increased T-cell and antibody responses; secondary endpoints included progression-free (PFS)/overall survival (OS), and anti-5T4 responses over the trial period. Results: CPM depleted Tregs in 21/27 patients during treatment week 3 (p=0.0045), resulting in significantly prolonged PFS amongst groups 2&4 over group 1 (5.0 vs. 2.5 months, HR=0.17 95% CI 0.048-0.62, p=0.0072). TroVax induced a >2-fold increase in anti-5T4 immune responses in 15/36 group 3&4 patients; these patients experienced significantly prolonged median PFS (6.5 vs. 2.4 months, HR 0.31 95% CI 0.14-0.65, p=0.0022) and OS (20 vs. 12 months, HR=0.37 95% CI 0.17-0.82, p=0.014). Combination of CPM & TroVax was not significantly superior. The primary endpoint at a single timepoint was not met since CPM-induced responses declined by week 7, and TroVax-induced responses were greatest at weeks 10-16. No serious adverse events were reported. Conclusions: Both CPM and TroVax induced highly beneficial anti-tumor immune responses resulting in significantly prolonged survival of end-stage CRC patients without toxicity. This is the first study to show a clear benefit of immunotherapy in advanced CRC, and suggests this approach may be superior (and less toxic) to continuous palliative chemotherapy in these patients. Clinical trial information: 54669986.

Models of Thermodynamic Properties of Prominences

1979 ◽  
Vol 44 ◽  
pp. 349-355
Author(s):  
R.W. Milkey
Keyword(s):  
Thermodynamic Properties ◽  
Mass Transport ◽  
Emission Spectrum ◽  
Thermodynamic Parameters ◽  
Working Group ◽  
Physical Processes ◽  
Theoretical Concepts ◽  
Group 3 ◽  
Observational Techniques

The focus of discussion in Working Group 3 was on the Thermodynamic Properties as determined spectroscopically, including the observational techniques and the theoretical modeling of physical processes responsible for the emission spectrum. Recent advances in observational techniques and theoretical concepts make this discussion particularly timely. It is wise to remember that the determination of thermodynamic parameters is not an end in itself and that these are interesting chiefly for what they can tell us about the energetics and mass transport in prominences.

Morphological Changes in the Rat Granulosa Cell Surface During Differentiation Induced by Estradiol and Gonadotropins

1977 ◽  
Vol 35 ◽  
pp. 484-485
Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley
Keyword(s):  
Cell Surface ◽  
Granulosa Cell ◽  
Morphological Changes ◽  
Follicular Development ◽  
Female Rats ◽  
Functional Changes ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.

Correlation of γ-radioactivity and Scanning Electron Microscopy in measurement of retention of 111Indium-labeled canine endothelial cells on synthetic vascular grafts

1989 ◽  
Vol 47 ◽  
pp. 886-887
Author(s):  
E.J. Prendiville ◽  
S. Laliberté Verdon ◽  
K. E. Gould ◽  
K. Ramberg ◽  
R. J. Connolly ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ex Vivo ◽  
Vascular Grafts ◽  
Retention Data ◽  
Vascular Prostheses ◽  
Group 4 ◽  
Human Fibronectin ◽  
Insufficient Time ◽  
Group 3 ◽  
Group 2

Endothelial cell (EC) seeding is postulated as a mechanism of improving patency in small caliber vascular grafts. However the majority of seeded EC are lost within 24 hours of restoration of blood flow in previous canine studies . We postulate that the cells have insufficient time to fully develop their attachment to the graft surface prior to exposure to hemodynamic stress. We allowed EC to incubate on fibronectin-coated ePTFE grafts for four different time periods after seeding and measured EC retention after perfusion in a canine ex vivo shunt circuit.Autologous canine EC, were enzymatically harvested, grown to confluence, and labeled with 30 μCi 111 Indium-oxine/80 cm 2 flask. Four groups of 5 cm x 4 mm ID ePTFE vascular prostheses were coated with 1.5 μg/cm.2 human fibronectin, and seeded with 1.5 x 105 EC/ cm.2. After seeding grafts in Group 1 were incubated in complete growth medium for 90 minutes, Group 2 were incubated for 24 hours, Group 3 for 72 hours and Group 4 for 6 days. Grafts were then placed in the canine ex vivo circuit, constructed between femoral artery and vein, and subjected to blood flow of 75 ml per minute for 6 hours. Continuous counting of γ-activity was made possible by placing the seeded graft inside the γ-counter detection crystal for the duration of perfusion. EC retention data after 30 minutes, 2 hours and 6 hours of flow are shown in the table.

A Phonomotor Approach to Apraxia of Speech Treatment

2020 ◽  
Vol 29 (4) ◽  
pp. 2109-2130
Author(s):  
Lauren Bislick
Keyword(s):  
Phase I ◽  
Treatment Effects ◽  
Single Case ◽  
Motor Planning ◽  
The Other ◽  
Multimodal Approach ◽  
Apraxia Of Speech ◽  
Duration Of Treatment ◽  
Treatment Gains ◽  
Future Work

Purpose This study continued Phase I investigation of a modified Phonomotor Treatment (PMT) Program on motor planning in two individuals with apraxia of speech (AOS) and aphasia and, with support from prior work, refined Phase I methodology for treatment intensity and duration, a measure of communicative participation, and the use of effect size benchmarks specific to AOS. Method A single-case experimental design with multiple baselines across behaviors and participants was used to examine acquisition, generalization, and maintenance of treatment effects 8–10 weeks posttreatment. Treatment was distributed 3 days a week, and duration of treatment was specific to each participant (criterion based). Experimental stimuli consisted of target sounds or clusters embedded nonwords and real words, specific to each participants' deficit. Results Findings show improved repetition accuracy for targets in trained nonwords, generalization to targets in untrained nonwords and real words, and maintenance of treatment effects at 10 weeks posttreatment for one participant and more variable outcomes for the other participant. Conclusions Results indicate that a modified version of PMT can promote generalization and maintenance of treatment gains for trained speech targets via a multimodal approach emphasizing repeated exposure and practice. While these results are promising, the frequent co-occurrence of AOS and aphasia warrants a treatment that addresses both motor planning and linguistic deficits. Thus, the application of traditional PMT with participant-specific modifications for AOS embedded into the treatment program may be a more effective approach. Future work will continue to examine and maximize improvements in motor planning, while also treating anomia in aphasia.

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