scholarly journals P33: EARLY RESULTS OF AN IN VIVO AND IN VITRO ALLERGY TESTING PROTOCOL FOR COVID‐19 VACCINATIONS

2021 ◽  
Vol 51 (S4) ◽  
pp. 14-14
Keyword(s):  
Allergy Testing ◽  
Testing Protocol ◽  
Early Results

Antitumor activity of esorubicin in human tumor clonogenic assay with comparisons to doxorubicin.

1984 ◽  
Vol 2 (4) ◽  
pp. 282-286 ◽  
Author(s):  
S E Salmon ◽  
L Young ◽  
B Soehnlen ◽  
R Liu
Keyword(s):  
Antitumor Activity ◽  
Clonogenic Assay ◽  
Human Tumor ◽  
Therapeutic Index ◽  
In Vivo Studies ◽  
Early Results ◽  
Colony Forming Units ◽  
Human Solid Tumors

The new anthracycline analog, esorubicin (4'deoxy-doxorubicin, ESO), was tested against fresh biopsies of human solid tumors in vitro in clonogenic assay and the results were contrasted to those obtained with doxorubicin (DOX). ESO appeared to be significantly more potent on a weight basis than DOX in these studies, and exhibited a spectrum of antitumor activity in vitro that was in general qualitatively similar to that observed with DOX. In vitro antitumor activity was observed in a wide variety of human cancers including anthracycline-sensitive tumor types. ESO has previously been reported to have decreased cardiac toxicity in preclinical models as compared to DOX. Comparative testing of these anthracyclines on granulocyte-macrophage colony-forming units (GM-CFUs) and tumor colony forming units (TCFUs) indicated that the in vitro GM-CFU assay is more sensitive to these myelosuppressive drugs than are TCFUs, and underscores the need for in vivo studies to determine normal tissue toxicity and the therapeutic index of a drug. Early results of phase I studies suggest that with respect to myelosuppression, the maximally tolerated dose of ESO will be about half that of DOX. The increased in vitro antitumor potency observed for ESO and a spectrum of activity (even at one half the dose of DOX) supports the broad testing of ESO in the clinic to determine whether it will prove to be a more effective and less toxic anthracycline.

Arsenic Trioxide Shows Synergistic Anti-Myeloma Effects When Combined with Bortezomib and Melphalan In Vitro and Helps Overcome Resistance of Multiple Myeloma Cells to These Treatments in Vivo.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2467-2467
Author(s):  
Richard A. Campbell ◽  
Haiming Chen ◽  
Daocheng Zhu ◽  
Janice C. Santos ◽  
Benjamin Bonavida ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Cell Lines ◽  
Combined Therapy ◽  
In Vivo Studies ◽  
Low Doses ◽  
Drug Resistant ◽  
Early Results ◽  
Post Implantation

Abstract Arsenic trioxide (ATO) induces apoptosis of plasma cells through a number of mechanisms including inhibiting DNA binding by NF-κB. These results suggest that this agent may be synergistic when combined with other active anti-myeloma drugs. To evaluate this we examined the effect of ATO alone and in combination with anti-myeloma treatments evaluated in vitro with MTT assays and using our severe combined immunodeficient (SCID)-hu murine myeloma models. First, we determined the effects of combining ATO with bortezomib or melphalan on the myeloma cell lines RPMI8226 and U266. Cell proliferation assays demonstrated marked synergistic anti-proliferative effects of ATO at concentrations ranging from 5x10−5M – 5x10−9M and melphalan concentrations ranging from 3x10−5M – 3x10−9M. Similar effects were observed when these cell lines were treated with bortezomib and varying concentrations of ATO (5x10−5 M – 5x10−10 M). We also investigated the potential of ATO to increase the efficacy of anti-myeloma therapies in our SCID-hu murine model LAGλ–1 (Yang H et al. Blood 2002). Each SCID mouse was implanted with a 0.5 cm3 LAGλ–1 tumor fragment into the left hind limb muscle. Mice were treated with ATO alone at 6.0 mg/kg, 1.25 mg/kg, 0.25 mg/kg, and 0.05 mg/kg intraperitoneally (IP) daily x5/week starting 19 days post-implantation. Mice receiving the highest dose of ATO (6.0 mg/kg) showed marked inhibition of tumor growth and reduction of paraprotein levels while there was no effect observed in all other treatment groups. Next, 27 days following implantation of our LAGλ–1 intramuscular (IM) tumor, LAGλ–1 mice were treated with ATO (1.25 mg/kg) IP, bortezomib (0.25 mg/kg), or the combination of both drugs at these doses in the schedules outlined above. ATO or bortezomib treatment alone had no anti-myeloma effects at these low doses consistent with our previous results whereas there was a marked decrease in both tumor volume (57%) and paraprotein levels (53%) in mice receiving the combined therapy. The combination of melphalan and ATO was also evaluated in this model. LAGλ–1 bearing mice received therapy with melphalan IP x1/weekly at 12.0 mg/kg, 6.0 mg/kg, 0.6 mg/kg, and 0.06 mg/kg starting 22 days post-implantation and showed no anti-myeloma effects. Twenty-eight days following implantation of LAGλ–1 tumor, mice received ATO (1.25 mg/kg) or melphalan (0.6 mg/kg) alone at doses without anti-myeloma effects, or the combination of these agents at these doses. The animals treated with these drugs alone showed a similar growth and increase in paraprotein levels to control mice whereas the combination of ATO and melphalan at these low doses markedly suppressed the growth of the tumor by >50% and significantly reduced serum paraprotein levels. These in vitro and in vivo studies suggest that the addition of ATO to other anti-myeloma agents is likely to result in improved outcomes for patients with drug resistant myeloma. Based on these results, these combinations are now in clinical trials with promising early results for patients with drug resistant myeloma.

A Protocol to Evaluate Semi-Rigid Pedicle Screw Systems

1997 ◽  
Vol 119 (3) ◽  
pp. 364-366 ◽  
Author(s):  
J. D. Clausen ◽  
V. K. Goel ◽  
K. Sairyo ◽  
M. Pfeiffer
Keyword(s):  
Pedicle Screw ◽  
In Vitro Testing ◽  
Cable System ◽  
Spinal Implants ◽  
Testing Protocol

The objective of the current study was to develop an in vitro testing protocol to evaluate semi-rigid pedicle screw devices. A corpectomy model protocol exists to evaluate rigid spinal implants; however, semi-rigid devices are contraindicated for this condition. This paper describes a technique that simulates more closely the conditions a semi-rigid device would see in vivo. Finally, the new testing protocol is used to evaluate the DDS® pedicle screw-cable system. Benefits and shortcomings of the new protocol are discussed.

Role for IL2 adjunctive cotherapy for suppression of a solid tumor with designer T cells: Phase I trial data in prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 216-216
Author(s):  
Richard Paul Junghans
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Phase I ◽  
Phase I Trial ◽  
Immune Therapy ◽  
Antigen Receptors ◽  
Activated T Cells ◽  
Early Results

216 Background: We created chimeric antigen receptors (CAR) against prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” (dTc) kill prostate cancer cells in vitro and in vivo in animal models (Ma et al. Prostate2004:61:12-25). A Phase I trial was performed. Methods: Patient T cells are retrovirally transduced and expanded ex vivoto span doses of 10^9 to 10^10 T cells. Patients undergo prior non-myeloablative (NMA) conditioning to create a “hematologic space” into which dTc are infused for stable engraftment and prolonged in vivo efficacy. Continuous infusion low dose IL2 (LDI: 75 kiu/kg/d) is administered. Results: Infused T cells were documented. Safety was shown and partial responses (PR) obtained in 2/5 subjects (40%), with PSA suppressions of 50-70% over 1-2+ mo and PSA progression delay up to 150d. Against expectation, response correlated inversely with engraftment (p=0.06) but directly with plasma IL2 (p=0.03) that was as much as 20-fold lower in non-responders than responders. Low plasma IL2 correlated with high engraftments (p<0.01), prompting an hypothesis that high engrafted numbers of activated T cells absorb out IL2 to a level too low to sustain dTc activation for tumor killing. Conclusions: Encouraging early results were obtained with anti-PSMA dTc in adoptive immune therapy of advanced prostate cancer. It is proposed that adequate higher plasma IL2 will reveal the expected greater potency of higher dTc doses, thereby potentially inducing PSA reductions of 100%, with durable remissions. A study redesign tests moderate dose IL2 (MDI) (300 kiu/kg/8h bolus) versus LDI in a randomized Pilot at the 10^10 cell dose, which is now open to enrolment. To refer patients, please contact the study referral manager by telephone: 401-456-2507 or email: [email protected]. This trial received partial funding from US Army/DOD. Preclinical work was supported by Prostate Cancer Foundation. Clinical trial information: NCT00664196.

Ascorbic Acid Overcomes Drug Resistance in Myeloma and Significantly Increases the Anti-Myeloma Effects of both Arsenic Trioxide and Melphalan in Vitro and in Vivo.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2470-2470 ◽  
Author(s):  
Richard A. Campbell ◽  
Haiming Chen ◽  
Daocheng Zhu ◽  
Janice C. Santos ◽  
Benjamin Bonavida ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Arsenic Trioxide ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Myeloma Cell ◽  
Tumor Burden ◽  
Early Results ◽  
Mtt Assays

Abstract Glutathione levels have previously been shown to be associated with the development of resistance to a variety of anti-myeloma therapies. Ascorbic acid (AA) depletes intracellular glutathione levels which, in turn, should increase the sensitivity of tumor cells to anti-myeloma agents such as arsenic trioxide (ATO) and melphalan. To determine the synergistic effects of combining AA, with ATO and/or melphalan, we evaluated the effects of these combinations with MTT assays on myeloma cell lines in vitro and using our severe combined immunodeficient (SCID)-hu murine myeloma models. We determined the synergistic effects of combining AA with ATO and/or melphalan on the myeloma cell lines RPMI8226, 8226/dox, U266, and U266/dox in vitro. MTT assays demonstrated marked synergistic anti-proliferative effects of AA at 10 mM when added to these cell lines in the presence of ATO concentrations ranging from 5x10−5 M – 5x10−9 M, and melphalan concentrations ranging from 3x10−5 M – 3x10−9 M. In order to provide further evidence for the clinical relevance of these synergistic effects of AA, we investigated the potential of AA to increase the efficacy of current anti-myeloma therapies in our SCID-hu murine model of human myeloma LAGλ–1 (Yang H et al. Blood 2002). Each SCID mouse was implanted with a 0.5 cm3 LAGλ–1 tumor fragment into the left hind limb muscle. Twenty-eight days following implantation, mice then received treatment intraperitoneally (IP) with either AA (300 mg/kg) daily x5/week, ATO (1.25 mg/kg) daily x5/week, or melphalan (3.0 mg/kg) x1/week, or the combination of these agents. AA, ATO, and melphalan alone have no anti-myeloma effects at these doses, whereas AA+melphalan results in significantly decreased tumor burden and paraprotein levels. The most profound anti-myeloma effects were observed in animals treated with all three drugs together. These data show not only the additional synergistic anti-myeloma effects of AA on both ATO and melphalan in vitro but for the first time suggest that these effects are also present in vivo. This provides the rationale for combining AA with these agents in myeloma patients with resistant disease. In support of this, early results of clinical trials using the combination of AA, ATO and low doses of oral melphalan are promising.

scholarly journals Prick, patch or blood test? A simple guide to allergy testing

2021 ◽  
Vol 16 (2) ◽  
pp. 19-26
Author(s):  
Leelavathi Muthupalaniappen ◽  
Adawiyah Jamil
Keyword(s):  
Test Method ◽  
Type I ◽  
In Vitro Test ◽  
Delayed Reaction ◽  
Allergy Testing ◽  
Prick Test ◽  
Type Iv ◽  
Allergy Test

This article provides information on allergy testing and serves as a simple guide for physicians who are considering using allergy testing as a step in patient management. Basic principles of allergy testing, indications for testing, and how and when to choose a suitable allergy test are discussed. Allergy testing in general refers to evaluation of either type I or type IV hypersensitivity reactions. The type I (immediate) reaction is evaluated using the skin prick test (in vivo) or serum IgE (in vitro) test methods, while the type IV (delayed) reaction is determined via the skin patch test method. The allergens responsible for a specific reaction can be identified from allergy testing, and this information is useful in administering avoidance measures. Appropriate treatment of allergic reactions along with allergen avoidance ensure a successful treatment outcome and prevent future reactions.

Anti-AIDS agents show varying early results in vitro and in vivo

JAMA ◽  
1985 ◽  
Vol 254 (18) ◽  
pp. 2521-2521 ◽  
Author(s):  
D. E. Riesenberg
Keyword(s):  
Early Results

Allergy Testing: In Vivo Versus In Vitro

1988 ◽  
Vol 35 (5) ◽  
pp. 995-1009 ◽  
Author(s):  
Dennis R. Ownby
Keyword(s):  
Allergy Testing

scholarly journals Cannabinoids in the Pathophysiology of Skin Inflammation

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 652 ◽  
Author(s):  
Cristian Scheau ◽  
Ioana Anca Badarau ◽  
Livia-Gratiela Mihai ◽  
Andreea-Elena Scheau ◽  
Daniel Octavian Costache ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Synthetic Cannabinoids ◽  
Skin Inflammation ◽  
Cellular Mechanisms ◽  
Inflammatory Conditions ◽  
Early Results ◽  
Inflammatory Component

Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component. However, various studies cite conflicting results concerning the cellular mechanisms involved, while others suggest that cannabinoids may even exert pro-inflammatory behaviors. This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer. In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances. Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.

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