Publisher Correction: Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis

Abstract Purpose Guidelines recommend evaluating the risk of opioid-related adverse events prior to initiating opioid therapy. The orthopedic service at San Francisco Veterans Affairs Health Care System (SFVHCS) has not routinely used risk assessment tools such as the Stratification Tool for Opioid Risk Mitigation, prescription drug monitoring program data, and urine drug screening prior to opioid prescribing. A quality improvement project was conducted to evaluate the number of pharmacist-provided opioid risk mitigation recommendations implemented by orthopedic providers for patients who underwent total hip or knee arthroplasty at SFVHCS. Summary A pharmacist-led workflow for completing risk mitigation reviews was developed in collaboration with orthopedic providers, and urine drug screening was added to the preoperative laboratory testing protocol. The following recommendations were communicated via electronic medical record: limit postoperative opioids to a 7- or 14-day supply based on risk of suicide and/or overdose, offer naloxone and a medication disposal bag, and order a urine drug screen if not already completed. Risk reviews were completed for 75 patients. Among 64 patients with 2-month postdischarge data available, 88% (7 of 8) of 7-day and 79% (44 of 56) of 14-day opioid supply recommendations were implemented; 41% (26 of 59) of recommendations to issue a medication disposal bag, 17% (2 of 12) recommendations to order a missing urine drug screen, and 9% (5 of 55) of recommendations to offer naloxone were implemented. Conclusion Pharmacist-performed risk mitigation reviews paired with individualized recommendations led to high rates of orthopedic provider acceptance of limiting postdischarge opioid day supplies for patients who had total hip or knee arthroplasty. Alternative strategies may increase access to naloxone. Future research should examine the impact of risk mitigation tools in reducing prescribing of long-term opioid therapy and adverse events among orthopedic surgical patients.

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Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma

EBioMedicine ◽

10.1016/j.ebiom.2021.103510 ◽

2021 ◽

Vol 70 ◽

pp. 103510

Author(s):

Yin Li ◽

Fengkai Xu ◽

Fanghua Chen ◽

Yiwei Chen ◽

Di Ge ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Drug Screen

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Gatifloxacin Interference with Opiate Urine Drug Screen

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy ◽

10.1592/phco.26.3.435 ◽

2006 ◽

Vol 26 (3) ◽

pp. 435-439 ◽

Cited By ~ 16

Author(s):

Craig M Straley ◽

Eric J Cecil ◽

Mark P Herriman

Keyword(s):

Drug Screen ◽

Urine Drug Screen ◽

Urine Drug

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Interleukin-6 Inhibits Fas-Induced Apoptosis and Stress-Activated Protein Kinase Activation in Multiple Myeloma Cells

Blood ◽

10.1182/blood.v89.1.227 ◽

1997 ◽

Vol 89 (1) ◽

pp. 227-234 ◽

Cited By ~ 185

Author(s):

Dharminder Chauhan ◽

Surender Kharbanda ◽

Atsushi Ogata ◽

Mitsuyoshi Urashima ◽

Gerrard Teoh ◽

...

Keyword(s):

Multiple Myeloma ◽

Protein Kinase ◽

Dna Fragmentation ◽

P38 Mapk ◽

Interleukin 6 ◽

Early Response ◽

Mitogen Activated Protein Kinase ◽

Serum Starvation ◽

Mapk Activity ◽

Induced Apoptosis

Abstract Fas belongs to the family of type-1 membrane proteins that transduce apoptotic signals. In the present studies, we characterized signaling during Fas-induced apoptosis in RPMI-8226 and IM-9 multiple myeloma (MM) derived cell lines as well as patient plasma cell leukemia cells. Treatment with anti-Fas (7C11) monoclonal antibody (MoAb) induced apoptosis, evidenced by internucleosomal DNA fragmentation and propidium iodide staining, and was associated with increased expression of c-jun early response gene. We also show that anti-Fas MoAb treatment is associated with activation of stress-activated protein kinase (SAPK) and p38 mitogen-activated protein kinase (MAPK); however, no detectable increase in extracellular signal-regulated kinases (ERK1 and ERK2) activity was observed. Because interleukin-6 (IL-6) is a growth factor for MM cells and inhibits apoptosis induced by dexamethasone and serum starvation, we examined whether IL-6 affects anti-Fas MoAb-induced apoptosis and activation of SAPK or p38 MAPK in MM cells. Culture of MM cells with IL-6 before treatment with anti-Fas MoAb significantly reduced both DNA fragmentation and activation of SAPK, without altering induction of p38 MAPK activity. These results therefore suggest that anti-Fas MoAb-induced apoptosis in MM cells is associated with activation of SAPK, and that IL-6 may both inhibit apoptosis and modulate SAPK activity.

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Interleukin-13 affects the epithelial sodium channel in the intestine by coordinated modulation of STAT6 and p38 MAPK activity

The Journal of Physiology ◽

10.1113/jp271156 ◽

2015 ◽

Vol 593 (24) ◽

pp. 5269-5282 ◽

Cited By ~ 22

Author(s):

Petra Dames ◽

Theresa Bergann ◽

Anja Fromm ◽

Roland Bücker ◽

Christian Barmeyer ◽

...

Keyword(s):

Sodium Channel ◽

P38 Mapk ◽

Epithelial Sodium Channel ◽

Interleukin 13 ◽

Mapk Activity

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Spheroid-based drug screen: considerations and practical approach

Nature Protocols ◽

10.1038/nprot.2008.226 ◽

2009 ◽

Vol 4 (3) ◽

pp. 309-324 ◽

Cited By ~ 879

Author(s):

Juergen Friedrich ◽

Claudia Seidel ◽

Reinhard Ebner ◽

Leoni A Kunz-Schughart

Keyword(s):

Practical Approach ◽

Drug Screen

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Gab1 and SHP-2 promote Ras/MAPK regulation of epidermal growth and differentiation

The Journal of Cell Biology ◽

10.1083/jcb.200205017 ◽

2002 ◽

Vol 159 (1) ◽

pp. 103-112 ◽

Cited By ~ 57

Author(s):

Ti Cai ◽

Keigo Nishida ◽

Toshio Hirano ◽

Paul A. Khavari

Keyword(s):

Epidermal Cell ◽

Mapk Signaling ◽

Dominant Negative ◽

Mapk Activity ◽

Ras Activation ◽

Proliferation And Differentiation ◽

Epidermal Proliferation ◽

Epidermal Growth ◽

Docking Protein

În epidermis, Ras can influence proliferation and differentiation; however, regulators of epidermal Ras function are not fully characterized, and Ras effects on growth and differentiation are controversial. EGF induced Ras activation in epidermal cells along with phosphorylation of the multisubstrate docking protein Gab1 and its binding to SHP-2. Expression of mutant Gab1Y627F deficient in SHP-2 binding or dominant-negative SHP-2C459S reduced basal levels of active Ras and downstream MAPK proteins and initiated differentiation. Differentiation triggered by both Gab1Y627F and SHP-2C459S could be blocked by coexpression of active Ras, consistent with Gab1 and SHP-2 action upstream of Ras in this process. To study the role of Gab1 and SHP-2 in tissue, we generated human epidermis overexpressing active Gab1 and SHP-2. Both proteins stimulated proliferation. In contrast, Gab1Y627F and SHP-2C459S inhibited epidermal proliferation and enhanced differentiation. Consistent with a role for Gab1 and SHP-2 in sustaining epidermal Ras/MAPK activity, Gab1−/− murine epidermis displayed lower levels of active Ras and MAPK with postnatal Gab1−/− epidermis, demonstrating the hypoplasia and enhanced differentiation seen previously with transgenic epidermal Ras blockade. These data provide support for a Ras role in promoting epidermal proliferation and opposing differentiation and indicate that Gab1 and SHP-2 promote the undifferentiated epidermal cell state by facilitating Ras/MAPK signaling.

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