Publications by authors named "Junan Li"

73 Publications

Adjuvant radiation and cetuximab improves local control in head and neck cutaneous squamous cell carcinoma: A phase II study.

Head Neck 2021 Aug 7. Epub 2021 Aug 7.

Department of Radiation Oncology, University of Cincinnati, Cincinnati, Ohio, USA.

Background: Cutaneous squamous cell carcinoma of the head/neck (CSCCHN) is common due to chronic sun exposure. As CSCCHN highly expresses EGFR, we prospectively studied postoperative concurrent cetuximab with radiotherapy for locally advanced CSCCHN (LA-CSCCHN).

Materials And Methods: Single-institutional phase II trial of LA-CSCCHN (NCT XXXX). Adjuvant radiation was given with concurrent cetuximab. Primary endpoint of 2-year LRC and secondary objectives of 2-year disease-free survival (DFS) and 2-year OS were assessed by Kaplan-Meier analysis.

Results: Twenty-four patients ages 47-88 (median 71 years) were treated from 2014 to 2017. Fourteen patients had T3/4 disease, 5 had N1 disease, and 7 were N2/3. At median follow-up of 42 months, median OS and DFS was not reached and 64 months. Two-year OS was 75%, 2-year DFS was 70.8%. LRC was 91.1% at 2 years. All grade 3 adverse events were related to skin toxicity (12.5% radiation-related dermatitis, 16.7% cetuximab-related rash).

Conclusions: LRC compares favorably to historical data examining postoperative radiation alone but requires further investigation.
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http://dx.doi.org/10.1002/hed.26835DOI Listing
August 2021

Educating Pharmacy Students About Underserved Populations Using Patient Speakers and Simulation Activities.

Am J Pharm Educ 2021 Aug 22;85(7):8461. Epub 2021 Jul 22.

The Ohio State University, College of Pharmacy, Columbus, Ohio.

To assess the impact of the Patient Voices series on Doctor of Pharmacy (PharmD) students. A series of patient speakers and integrated simulation activities focused on underserved populations, otherwise known as the Patient Voices series, was embedded into a pharmacy skills laboratory curriculum. First-year PharmD students' self-ratings of confidence were compared on pre- and post-course surveys. Using evaluations from first-year introductory pharmacy practice experiences (IPPEs), student self-evaluation data were compared to preceptor evaluations of student performance. Open-ended responses to course evaluations from first- and second-year PharmD students and student reflections from third-year PharmD students were assessed using conventional content analysis to identify and characterize student perceptions. Significant increases were observed in first-year students' confidence to show empathy (mean, 4.2 to 4.7) and to interact with patients from underserved communities (mean, 2.2 to 4.2). Preceptor ratings of students' empathy were consistent with the students' self-rated abilities, while students' self-ratings on cultural sensitivity were higher than the preceptors' ratings. Qualitative analysis of course evaluation surveys and reflections revealed common themes identified by students, such as understanding different perspectives, increased empathy for patients, and the value of including this content in the curriculum. Student confidence to interact with patients from a variety of underserved populations increased following introduction of the Patient Voices series into the PharmD curriculum. Students perceived the series to be a valuable learning experience.
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http://dx.doi.org/10.5688/ajpe8461DOI Listing
August 2021

Synthesis and Antileishmanial Evaluation of Arylimidamide-Azole Hybrids Containing a Phenoxyalkyl Linker.

ACS Infect Dis 2021 07 4;7(7):1901-1922. Epub 2021 Feb 4.

Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.

Due to the limitations of existing medications, there is a critical need for new drugs to treat visceral leishmaniasis. Since arylimidamides and antifungal azoles both show oral activity in murine visceral leishmaniasis models, a molecular hybridization approach was employed where arylimidamide and azole groups were separated by phenoxyalkyl linkers in an attempt to capitalize on the favorable antileishmanial properties of both series. Among the target compounds synthesized, a greater antileishmanial potency against intracellular was observed as the linker length increased from two to eight carbons and when an imidazole ring was employed as the terminal group compared to a 1,2,4-triazole group. Compound (-(4-((8-(1-imidazol-1-yl)octyl)oxy)-2-isopropoxyphenyl) picolinimidamide) displayed activity against intracellular amastigotes with an IC value of 0.53 μM. When tested in a murine visceral leishmaniasis model, compound at a dose of 75 mg/kg/day p.o. for five consecutive days resulted in a modest 33% decrease in liver parasitemia compared to the control group, indicating that further optimization of these molecules is needed. While potent hybrid compounds bearing an imidazole terminal group were also strong inhibitors of recombinant CYP51 from , as assessed by a fluorescence-based assay, additional targets are likely to play an important role in the antileishmanial action of these compounds.
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http://dx.doi.org/10.1021/acsinfecdis.0c00855DOI Listing
July 2021

Comparison of subsequent infusion hypersensitivity reactions to paclitaxel using two different infusion strategies.

Support Care Cancer 2021 Aug 14;29(8):4423-4429. Epub 2021 Jan 14.

Department of Pharmacy, The Arthur G. James Cancer Hospital and Richard J. Solove Institute at The Ohio State University, 460 W 10th Avenue, C150, Columbus, OH, 43210, USA.

Purpose: The purpose of this study was to compare the incidence of rescue medication utilization with up to 3 subsequent doses of paclitaxel in patients who underwent an infusion rate escalation versus those who continued on the standard infusion rate after experiencing an initial paclitaxel infusion hypersensitivity reaction (HSR) requiring rescue medications.

Methods: A retrospective, single-center review was conducted on patients who experienced a paclitaxel infusion HSR requiring rescue medications to their first or second lifetime dose of paclitaxel.

Results: A total of 99 patients were included for analysis, and from this group, 22 patients were continued on the standard infusion rate, while 77 patients were changed to an infusion rate escalation. The rate of subsequent rescue medication utilization was 5% in patients who were continued at the standard infusion rate versus 23% in patients who were changed to an infusion rate escalation (p = 0.064). The incidence of subsequent rescue medication utilization was unrelated to disease stage (p = 0.39), the paclitaxel dosing regimen (p = 0.99), or a diagnosis of asthma (p = 0.99).

Conclusion: This single-center, retrospective study suggests that while not statistically significant, there was a potentially clinically meaningful increase in the rate of subsequent rescue medication utilization in patients who were changed to an infusion rate escalation compared to those who continued on the same standard infusion rate after experiencing an initial HSR to paclitaxel.
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http://dx.doi.org/10.1007/s00520-021-05991-7DOI Listing
August 2021

CRISPR/Cas9 Genome Editing of the Human Topoisomerase II Intron 19 5' Splice Site Circumvents Etoposide Resistance in Human Leukemia K562 Cells.

Mol Pharmacol 2021 03 14;99(3):226-241. Epub 2021 Jan 14.

Division of Pharmaceutics and Pharmacology, College of Pharmacy (V.A.H., J.C.-M., J.L.P., J.L., J.C.Y., T.S.E., N.S.) and Department of Biomedical Informatics, College of Medicine (H.G.O), The Ohio State University, Columbus, Ohio

An essential function of DNA topoisomerase II (TOP2; 170 kDa, TOP2/170) is to resolve DNA topologic entanglements during chromosome disjunction by introducing transient DNA double-stranded breaks. TOP2/170 is an important target for DNA damage-stabilizing anticancer drugs, whose clinical efficacy is compromised by drug resistance often associated with decreased TOP2/170 expression. We recently demonstrated that an etoposide-resistant K562 clonal subline, K/VP.5, with reduced levels of TOP2/170, expresses high levels of a novel C-terminal truncated TOP2 isoform (90 kDa, TOP2/90). TOP2/90, the translation product of a TOP2 mRNA that retains a processed intron 19 (I19), heterodimerizes with TOP2/170 and is a resistance determinant through a dominant-negative effect on drug activity. We hypothesized that genome editing to enhance I19 removal would provide a tractable strategy to circumvent acquired TOP2-mediated drug resistance. To enhance I19 removal in K/VP.5 cells, CRISPR/Cas9 was used to make changes (GAG//GTAA →GAG//GTAA ) in the TOP2 gene's suboptimal exon 19/intron 19 5' splice site (E19/I19 5' SS). Gene-edited clones were identified by quantitative polymerase chain reaction and verified by sequencing. Characterization of a clone with all TOP2 alleles edited revealed improved I19 removal, decreased TOP2/90 mRNA/protein, and increased TOP2/170 mRNA/protein. Sensitivity to etoposide-induced DNA damage (H2AX, Comet assays) and growth inhibition was restored to levels comparable to those in parental K562 cells. Together, the results indicate that our gene-editing strategy for optimizing the TOP2 E19/I19 5' SS in K/VP.5 cells circumvents resistance to etoposide and other TOP2-targeted drugs. SIGNIFICANCE STATEMENT: Results presented here indicate that CRISPR/Cas9 gene editing of a suboptimal exon 19/intron 19 5' splice site in the DNA topoisomerase II (TOP2) gene results in circumvention of acquired drug resistance to etoposide and other TOP2-targeted drugs in a clonal K562 cell line by enhancing removal of intron 19 and thereby decreasing formation of a truncated TOP2 90 kDa isoform and increasing expression of full-length TOP2 170 kDa in these resistant cells. Results demonstrate the importance of RNA processing in acquired drug resistance to TOP2-targeted drugs.
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http://dx.doi.org/10.1124/molpharm.120.000173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919865PMC
March 2021

EMT-Induced Gemcitabine Resistance in Pancreatic Cancer Involves the Functional Loss of Equilibrative Nucleoside Transporter 1.

Mol Cancer Ther 2021 02 9;20(2):410-422. Epub 2020 Dec 9.

Division of Pharmaceutics and Pharmacology, The Ohio State University College of Pharmacy, Columbus, Ohio.

Epithelial-mesenchymal transition (EMT) in cancer cells drives cancer chemoresistance, yet the molecular events of EMT that underpin the acquisition of chemoresistance are poorly understood. Here, we demonstrate a loss of gemcitabine chemosensitivity facilitated by human equilibrative nucleoside transporter 1 (ENT1) during EMT in pancreatic cancer and identify that cadherin switching from the epithelial (E) to neuronal (N) type, a hallmark of EMT, contributes to this loss. Our findings demonstrate that N-cadherin decreases ENT1 expression, membrane localization, and gemcitabine transport, while E-cadherin augments each of these. Besides E- and N-cadherin, another epithelial cell adhesion molecule, EpCAM, played a more prominent role in determining ENT1 membrane localization. Forced expression of EpCAM opposed cadherin switching with restored ENT1 expression, membrane localization, and gemcitabine transport in EMT-committed pancreatic cancer cells. In gemcitabine-treated mice, EpCAM-positive tumors had high ENT1 expression and reduced metastasis, whereas tumors with N-cadherin expression resisted gemcitabine treatment and formed extensive secondary metastatic nodules. Tissue microarray profiling and multiplexed IHC analysis of pancreatic cancer patient-derived primary tumors revealed EpCAM and ENT1 cell surface coexpression is favored, and ENT1 plasma membrane expression positively predicted median overall survival times in patients treated with adjuvant gemcitabine. Together, our findings identify ENT1 as an inadvertent target of EMT signaling mediated by cadherin switching and provide a mechanism by which mesenchymal pancreatic cancer cells evade gemcitabine therapy during EMT.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0316DOI Listing
February 2021

Antiemetic medication efficacy during EPOCH and R-EPOCH treatment.

J Oncol Pharm Pract 2020 Oct 22:1078155220967722. Epub 2020 Oct 22.

The James Cancer Hospital, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.

Introduction: This study aims to determine the adequacy of current institutional standard practice for CINV prophylaxis for EPOCH and R-EPOCH at The Ohio State University James Cancer Hospital.

Methods: Single-center, retrospective analysis was performed including all patients receiving EPOCH or R-EPOCH chemotherapy for Non-Hodgkin's lymphomas from 1/1/2012 to 6/30/2017. The primary endpoint was rate of CINV events, which included usage of more than 50 percent of available doses of breakthrough antiemetics while inpatient, hospitalization due to CINV or related complications, or adjustments made to the CINV prophylactic or breakthrough regimen during current or subsequent cycles. Secondary endpoints included determining prescriber adherence to institutional standard CINV prophylaxis, characterization of adjustments to the antiemetic regimen following the incidence of CINV, and identification of high-risk patients that may benefit from additional CINV prophylaxis.

Results: Of 111 patients, 54 (48.6%) experienced CINV events with any cycle of EPOCH or R-EPOCH chemotherapy. Of those patients, 17 (31.5%) received institutional standard CINV prophylaxis at baseline, 8 (14.8%) received additional scheduled antiemetics, and 26 (48.1%) were prescribed additional breakthrough antiemetics with their first cycle of EPOCH or R-EPOCH. Younger age, diagnosis of anxiety, and previous susceptibility to nausea were significantly associated with CINV events.

Conclusion: This study illustrates the inadequacy of current institutional standard for CINV prophylaxis for patients receiving EPOCH and R-EPOCH, highly emetogenic chemotherapy regimens. With nearly half of included patients experiencing CINV events, and most initially receiving more than our standard prophylaxis, changes to our standard antiemetics used with this chemotherapy regimen are needed.
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http://dx.doi.org/10.1177/1078155220967722DOI Listing
October 2020

Assessment of pharmacy technician learning preferences and implications for training.

Am J Health Syst Pharm 2021 Feb;78(Suppl 1):S16-S25

Division of Pharmacy Practice and Science, Ohio State University College of Pharmacy, Columbus, OH.

Purpose: To assess pharmacy technician learning preferences using the VARK tool and through self-identification.

Methods: The VARK (visual, aural, read/write, kinesthetic) questionnaire was incorporated into a larger survey, which was distributed during live staff meetings and a continuing education session held by the Ohio Pharmacists Association attended by 204 pharmacy technicians across various practice settings.

Results: A 90% response rate was achieved. Most respondents (78.8%) self-identified a single predominant learning preference, with 60.3% indicating a preference for kinesthetic learning methods. In contrast, after assessment with the VARK questionnaire 37.9% of survey participants were categorized as having a quadmodal learning style incorporating all VARK modalities. With regard to the Pharmacy Technician Certification Exam, a large majority of participants (96.2% of those providing a response) indicated that they had taken the exam in the past, with 17 participants (9.3% of those providing a response) indicating more than 1 attempt to pass the exam. Furthermore, experiential (on-the-job) training was identified by a large majority of survey respondents (79.3%) as the preferred way to learn new information.

Conclusion: Learning preferences of pharmacy technicians vary amongst individuals, with many found to have multiple learning preferences through VARK questionnaire assessment. Incorporating experiential training and establishing learning preferences of pharmacy technicians may aid in development of accredited training programs that cater to the needs of pharmacy technicians.
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http://dx.doi.org/10.1093/ajhp/zxaa362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797731PMC
February 2021

Trends in anticoagulation management services following incorporation of direct oral anticoagulants at a large academic medical center.

J Thromb Thrombolysis 2021 May 9;51(4):1050-1058. Epub 2020 Oct 9.

The Ohio State University Wexner Medical Center, Columbus, OH, 43228, USA.

The introduction of direct oral anticoagulants (DOACs) to the market has expanded anticoagulation options for outpatient use. Routine evaluation by health care professionals is recommended as it is with warfarin, therefore requiring adjustments in practices of anticoagulation management services (AMS). This study aims to describe trends that occurred following the incorporation of DOACs into AMS at a large academic medical center. A retrospective chart review of pharmacist-run AMS was used to compare patients on DOAC therapy versus other types of anticoagulation, including warfarin and parenteral agents. Primary outcomes included trends in the number of unique patients, management encounters, and telephone encounters throughout the study period. Secondary outcomes included trends in new encounters, and changes in patient characteristics, resources utilized, and patient satisfaction scores. A total of 2976 unique patients, 74,582 management encounters, and 13,282 telephone encounters were identified. From study beginning to end, results showed stable numbers of unique patients, an increase in management encounters for the DOAC group and decrease in the other anticoagulants group, and stable numbers of telephone encounters. Additionally, the number of new encounters for both groups increased. Throughout the study, pharmacy resources were reallocated within anticoagulation to adapt to the changing trends and patient satisfaction reached targets. Patients' characteristics remained stable, with the DOAC group having fewer comorbid conditions and concomitant medications that could increase bleed risk. This study showed that by reallocating resources within anticoagulation, AMS can maintain stable patient populations while continuing to expand access and satisfy patients following DOAC inclusion.
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http://dx.doi.org/10.1007/s11239-020-02286-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546384PMC
May 2021

Association of Polymorphism With Overall Survival in Adult Patients With Hematologic Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation.

Anticancer Res 2020 Oct;40(10):5707-5713

Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.

Background/aim: Genetic variations of the non-coding RNA gene, ANRIL, have been associated with human diseases including cancer, type-2 diabetes, and atherosclerosis. In the present study, we investigated the potential associations of select ANRIL single nucleotide polymorphisms (SNPs) with overall survival and other clinical outcomes in adult patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Patients And Methods: Genomic DNA was extracted from whole blood samples from 103 adult patients with hematologic malignancies who had received allo-HSCT followed by oral tacrolimus therapy. The genotypes of four select ANRIL SNPs, rs564398, rs1063192, rs2151280, and rs2157719 were determined using qRT-PCR-based genotyping assays.

Results: rs2151280 (C->T) in ANRIL was associated with worse overall survival in these patients (CT/CC vs. TT). Contrarily, rs2151280 and the other select ANRIL SNPs were not associated with death at Day-100 after transplantation, the incidence of graft-versus-host disease (GVHD), acute kidney injury (AKI), and neurotoxicity in the study cohort.

Conclusion: rs2151280 represents a potential prognostic biomarker for overall survival in adult patients with hematologic malignancies after allo-HSCT.
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http://dx.doi.org/10.21873/anticanres.14585DOI Listing
October 2020

Evaluation of medication safety resources in pediatric hospitals.

Am J Health Syst Pharm 2020 08;77(Suppl 3):S78-S86

Department of Pharmacy, Nationwide Children's Hospital, Columbus, OH.

Purpose: As health systems continue to expand pharmacy and clinical services, the ability to evaluate potential medication safety risks and mitigate errors remains a high priority. Workload and productivity monitoring tools for the assessment of operational and clinical pharmacy services exist. However, such tools are not currently available to justify medication safety pharmacy services. The purpose of this study is to determine methods used to assess, allocate, and justify medication safety resources in pediatric hospitals.

Methods: A 32-question survey was designed and distributed utilizing the Research Electronic Data Capture (REDCap) tool. The survey was disseminated to 46 pediatric hospitals affiliated with the Children's Hospital Association (CHA). The survey was distributed in October 2018, and the respondents were given 3 weeks to submit responses. Data analysis includes the use of descriptive statistics. Categorical variables were summarized by frequencies and percentages to distinguish the differences between pediatric health systems.

Results: Of 26 respondents, 15.4% utilized metrics to justify medication safety resources. Metrics utilized were based on medication dispenses, projects, and error coding. Twenty-three percent of respondents were dissatisfied with current pharmacy-based medication safety resources within the organization. There was variability of medication safety resources within pediatric hospitals, including the number of dedicated full-time equivalents, time spent on tasks, and task prioritization.

Conclusion: Assessing medication safety resources at various pediatric hospitals highlights several potential barriers and opportunities. This information will serve as the foundation for the creation of a standardized workload assessment tool to assist pharmacy leaders with additional resource justification.
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http://dx.doi.org/10.1093/ajhp/zxaa177DOI Listing
August 2020

Endoscopic incision and selective cutting for primary treatment of benign esophageal anastomotic stricture: outcomes of 5 cases with a minimum follow-up of 12 months.

Ann Palliat Med 2020 May;9(3):1206-1210

Gastroenterology and Center of Digestive Endoscopy, the Second Hospital of Jilin University, Changchun 130041, China.

Background: Benign anastomotic esophageal stricture after surgical resection frequently occurs and requires endoscopic balloon dilation (EBD) or incision to maintain patency because of the significant recurrence rate. Our study was designed to evaluate the effectiveness and safety of endoscopic incision and selective cutting (EISC) as primary treatment on 5 patients for benign anastomotic esophageal stricture.

Methods: Five patients with benign stricture of the esophageal anastomosis after radical resection for esophageal cancer underwent EISC in our center between April, 2018 and January, 2019. The effectiveness and safety of the procedure were observed during at least 12 months follow-up.

Results: The EISC was successfully performed in all 5 patients. The diameters of the anastomoses were increased from 1-3 preoperatively to 14-18 mm (mean: 15.6 mm) intraoperatively (P<0.05). The duration of the operation ranged from 30-55 min (mean: 42.8 min). During at least 12 months follow-up observations, all patients resumed eating solid meals and had no recurrence of dysphagia.

Conclusions: EISC as primary treatment is a safe and effective treatment for benign anastomotic esophageal stricture.
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http://dx.doi.org/10.21037/apm-20-1090DOI Listing
May 2020

Risk Versus Benefit of Combined Aspirin and Warfarin Therapy in Patients With Atrial Fibrillation.

J Pharm Pract 2020 Apr 15:897190020916638. Epub 2020 Apr 15.

Ohio State University Wexner Medical Center, Columbus, OH, USA.

Purpose: Guidelines have differing recommendations for aspirin use in patients with an indication for anticoagulation. The purpose of this study was to evaluate the incidence of major bleeding and thromboembolic events (TEs) in patients with atrial fibrillation (AF) receiving warfarin alone (monotherapy group) versus warfarin plus aspirin (combination therapy group).

Methods: This was a retrospective, cohort study including patients from a pharmacist-run anticoagulation clinic. Inclusion criteria were patients with AF receiving anticoagulation between January 2013 and January 2014 observed over 5 years.

Results: One hundred forty-two patients were included in the combination group versus 89 in monotherapy group. In the combination group, 60 (42.3%) patients were on aspirin for no apparent indication, 19 (13.4%) had stable coronary artery disease and diabetes, and 26 (18.3%) had diabetes alone. Major bleeding occurred in 21 (14.9%) patients in the combination group versus 7 (7.9%) patients in the monotherapy group (odds ratio [OR] = 2.02, 95% confidence interval [CI]: 0.78-5.91; = .17). TE occurred in 10 (7%) patients in the combination group versus 4 (4.5%) in the monotherapy group (OR = 1.61, 95% CI: 0.44-7.24; = .57). There was no significant difference in bleeding ( = .85) or TE ( = .37) rates between aspirin indications in the combination group.

Conclusion: Combination therapy versus monotherapy may increase bleeding risk with little benefit in decreasing AF-related stroke or cardiovascular events.
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http://dx.doi.org/10.1177/0897190020916638DOI Listing
April 2020

MicroRNA-205 targets HER3 and suppresses the growth, chemosensitivity and metastasis of human nasopharyngeal carcinoma cells.

J BUON 2020 Jan-Feb;25(1):350-356

Department of Otolaryngology Head and Neck Surgery, the Second Hospital of Jilin University, Changchun, Ji Lin, China, 130000.

Purpose: Nasopharyngeal carcinoma is one of the lethal cancers prevalent in Southeast Asia and Southern China. The frequent relapses, development of drug resistance, the adverse effects of chemotherapy and lack of therapeutic targets form the major hurdles in nasopharyngeal carcinoma treatment. This study was undertaken to investigate the role and therapeutic potential of miR-205 in human nasopharyngeal carcinoma cells.

Methods: Expression analysis was performed by qRT-PCR. The WST-1 and colony formation assays were used for the assessment of the cell viability. Autophagy was detected by electron microscopy and apoptosis was detected by DAPI staining. Protein expression was determined by western blot analysis.

Results: The expression of miR-205 was significantly downregulated in human nasopharyngeal carcinoma cells. Overexpression of miR-205 caused significant inhibition in the proliferation of CNE1 nasopharyngeal carcinoma cells. The miR-205-triggered growth inhibition was found to be mainly due to the induction of autophagy which was associated with increase in LC3B II and decrease in p62 expression. The miR-205 overexpression also caused apoptotic cell death of CNE1 cells which was concomitant with increase in the Bax/Bcl-2 ratio. Additionally, miR-205 enhanced the chemosensitivity of the nasopharyngeal carcinoma cells to cisplatin and suppressed their migration and invasiveness. In silico analysis showed that miR-205 exerts its effects by inhibiting human epidermal growth factor receptor 3 (HER3). The expression of HER3 was found to be significantly upregulated in nasopharyngeal carcinoma cells and overexpression of HER3 could nullify the effects of miR-205 on the proliferation of nasopharyngeal carcinoma cells.

Conclusion: miR-205 may exhibit therapeutic implications in the treatment of nasopharyngeal carcinoma.
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December 2020

PTC209, a Specific Inhibitor of BMI1, Promotes Cell Cycle Arrest and Apoptosis in Cervical Cancer Cell Lines.

Anticancer Res 2020 Jan;40(1):133-141

Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.

Background/aim: Aberrant expression of the BMI1 oncogene has been prevalently found in a variety of human cancers, including cervical cancer. Recent studies have shown that PTC209, a specific BMI1 inhibitor, exhibits high potency in inhibiting the growth of colon, breast, oral cancer cells and cancer-initiating cells, indicative of its chemotherapeutic potential. In the current study, we evaluated the inhibitory abilities of PTC209 in cervical cancer cells.

Materials And Methods: Three cervical cell lines, C33A, HeLa, and SiHa were treated with PTC209. The impacts of PTC209 on BMI1 were investigated using quantitative reverse-transcription PCR assay (qRT-PCR) and western blotting; changes in cell viability, cell cycle distribution, and apoptosis were assessed using cell viability testing, colony formation assay and flow cytometry analyses, respectively.

Results: PTC209 exhibited considerably high short-term and long-term cytotoxicities in all tested cervical cancer cell lines regardless of their HPV infection status, TP53 and pRb statuses. PTC209 significantly downregulated the expression of BMI1 in cervical cancer cell lines, and such downregulation led to G0/G1 arrest (p<0.05). Moreover, PTC209 drove more cells into apoptosis (p<0.05).

Conclusion: PTC209 (BMI1-targeting agents, in general) represents a novel chemotherapeutic agent with potential in cervical cancer therapy.
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http://dx.doi.org/10.21873/anticanres.13934DOI Listing
January 2020

Cisplatin Induced the Expression of () Oncogene in Human Oral Squamous Cancer Cell Lines.

Anticancer Res 2020 Jan;40(1):67-73

Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.

Background/aim: Aberrant expression of the SEI1 oncogene has been prevalently found in a variety of human cancers, including oral squamous cell carcinoma (OSCC). Recent studies have shown that cisplatin up-regulates the expression of SEI1 in breast and bladder cancer cells, thus inhibiting apoptosis and cell death in these cells. In the present study, we investigated the impact of cisplatin on the expression of SEI1 in OSCC cells.

Materials And Methods: Four OSCC cell lines, CAL27, SCC4, SCC15, and SCC22A were treated with cisplatin and 5-fluorouracil, and changes in SEI1 expression in these cells were evaluated using quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analyses.

Results: Cisplatin significantly induced SEI1 expression in the tested OSCC cells. Contrarily, cisplatin treatment did not affect the expression of gankyrin and BMI1, two oncogenes frequently overexpressed in a coordinate manner with SEI1 in OSCC. Additionally, 5-fluorouracil did not bring about any detectable changes in SEI1 expression in these cells.

Conclusion: Cisplatin-induced up-regulation of SEI1 expression in OSCC is specific, and such induction could underlie the development of resistance to cisplatin in OSCC.
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http://dx.doi.org/10.21873/anticanres.13926DOI Listing
January 2020

A team-based learning approach to interprofessional education of medical and pharmacy students.

Curr Pharm Teach Learn 2019 Nov 9;11(11):1190-1195. Epub 2019 Aug 9.

The Ohio State University College of Pharmacy, 500 W 12th Ave, Columbus, OH 43210, United States. Electronic address:

Background: As collaborative team-based healthcare expands, there is a need for effective interprofessional education (IPE). Although the desired outcomes of IPE are defined by the Interprofessional Education Collaborative (IPEC), resources often limit IPE implementation. The purpose of this study is to assess the effectiveness of a novel interprofessional activity in improving health professions students' interprofessional competencies using team-based learning (TBL).

Interprofessional Education Activity: Teams of second year pharmacy and medical students participated in a novel IPE session targeting roles and responsibilities. This activity was designed and implemented by a small number of faculty and used TBL to educate a large number of students using limited resources. Class averages for individual and team readiness assurance test (iRAT/tRAT) scores were collected, and students were invited to complete the Interprofessional Collaborative Competencies Attainment Survey (ICCAS) to evaluate the effectiveness of the activity.

Discussion: On average, tRAT scores were 20% higher than iRAT scores. While there was significant improvement for all items on the ICCAS, questions within the roles and responsibilities domain of the ICCAS were most affected.

Implications: This novel IPE activity was successful in teaching a large group of professional students in the targeted domain of roles and responsibilities in a single session. This activity was a rich experience in which students learned together using limited resources which can be easily replicated at other institutions to help professional students gain proficiency in interprofessional competencies.
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http://dx.doi.org/10.1016/j.cptl.2019.07.010DOI Listing
November 2019

Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer.

Nano Res 2019 Apr 1;12(4):855-861. Epub 2019 Feb 1.

Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.

Triple-negative breast cancer (TNBC) is one type of the most aggressive breast cancers with poor prognosis. It is of great urgency to develop new therapeutics for treating TNBC. Based on current treatment guideline and genetic information of TNBC, a combinational therapy platform integrating chemotherapy drugs and mRNA encoding tumor suppressor proteins may become an efficacious strategy. In this study, we developed paclitaxel amino lipid (PAL) derived nanoparticles (NPs) to incorporate both chemotherapy drugs and P53 mRNA. The PAL P53 mRNA NPs showed superior properties compared to Abraxane and Lipusu used in the clinic including high paclitaxel loading capacity (24 wt.%, calculated by paclitaxel in PAL), PAL encapsulation efficiency (94.7% ± 6.8%) and mRNA encapsulation efficiency (88.7% ± 0.7%). Meanwhile, these NPs displayed synergetic cytotoxicity of paclitaxel and P53 mRNA in cultured TNBC cells. More importantly, we demonstrated anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. Overall, these chemotherapy drugs derived mRNA NPs provide a new platform to integrate chemotherapy and personalized medicine using tumor genetic information, and therefore represent a promising approach for TNBC treatment.
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http://dx.doi.org/10.1007/s12274-019-2308-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858063PMC
April 2019

Synthesis and antileishmanial evaluation of thiazole orange analogs.

Bioorg Med Chem Lett 2020 01 4;30(1):126725. Epub 2019 Oct 4.

Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, USA. Electronic address:

Cyanine compounds have previously shown excellent in vitro and promising in vivo antileishmanial efficacy, but the potential toxicity of these agents is a concern. A series of 22 analogs of thiazole orange ((Z)-1-methyl-4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium salt), a commercial cyanine dye with antileishmanial activity, were synthesized in an effort to increase the selectivity of such compounds while maintaining efficacy. Cyanines possessing substitutions on the quinolinium ring system displayed potency against Leishmania donovani axenic amastigotes that differed little from the parent compound (IC 12-42 nM), while ring disjunction analogs were both less potent and less toxic. Changes in DNA melting temperature were modest when synthetic oligonucleotides were incubated with selected analogs (ΔTm ≤ 5 °C), with ring disjunction analogs showing the least effect on this parameter. Despite the high antileishmanial potency of the target compounds, their toxicity and relatively flat SAR suggests that further information regarding the target(s) of these molecules is needed to aid their development as antileishmanials.
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http://dx.doi.org/10.1016/j.bmcl.2019.126725DOI Listing
January 2020

XRCC1-mediated DNA repair is associated with progression-free survival of multiple myeloma patients after autologous stem cell transplant.

Mol Carcinog 2019 12 22;58(12):2327-2339. Epub 2019 Sep 22.

Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio.

Autologous stem cell transplant (ASCT) with high-dose melphalan (HDM) is the standard treatment for fit multiple myeloma (MM) patients. It is generally believed that some DNA repair proteins impact the activity to repair melphalan-induced DNA damage, thus potentially contributing to the patient's clinical response. However, knowledge of these proteins is limited. In the current study, we investigated the roles of XRCC1, a protein involved in base excision repair and single-strand break repair, in melphalan response in MM cells. Small interfering RNA knockdown of XRCC1 significantly increased the accumulation of melphalan-induced DNA damage in MM cells and sensitized them to melphalan treatment, indicating that genetic variation in XRCC1 may impact response to melphalan treatment. We then evaluated the association between an XRCC1 variant with reduced activity, rs25487 (R399Q), and clinical outcomes of 108 MM patients with melphalan therapy. Our results showed that XRCC1 rs25487 was associated with prolonged progression-free survival (PFS) in MM patients. The adjusted hazard ratio for PFS between patients carrying rs25487 AA/AG and GG was 0.42 (95% confidence interval: 0.25, 0.84, P = .014). Taken together, these results indicate that XRCC1 is involved in the repair of melphalan-induced DNA damage and XRCC1 rs25487 variant with impaired DNA repair function influences the clinical responses of HDM in MM patients.
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http://dx.doi.org/10.1002/mc.23121DOI Listing
December 2019

Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer.

Clin Breast Cancer 2020 02 17;20(1):33-40. Epub 2019 Jul 17.

Department of Pharmacy, The Stefanie Spielman Comprehensive Breast Center, The James Cancer Hospital and Solove Research Institute at The Ohio State University Wexner Medical Center, Columbus, OH.

Background: Additional use of cyclin-dependent kinase 4/6 inhibitors with endocrine therapy improves progression-free survival (PFS) in advanced hormone receptor (HR)-positive HER2-negative breast cancer. However, neutropenia is a common reason for dose reductions, leading to concerns about palbociclib efficacy at lower doses. A safety analysis confirmed no PFS differences between palbociclib doses in the second-line setting, but to our knowledge, this has not been evaluated for first-line treatment.

Patients And Methods: In this retrospective, single-center cohort study we evaluated real-world use of first-line palbociclib with aromatase inhibitor (AI) treatment in HR-positive, HER2-negative metastatic breast cancer patients who received treatment between February 2015 and July 2017. The primary objective was to determine PFS of treatment with palbociclib and an AI in a real-world first-line setting. Secondary objectives included determining the PFS for patients treated with palbociclib on the basis of final doses, time to first dose reduction, time to treatment failure (TTF), and safety.

Results: Seventy patients were included in the final analysis. Median PFS was 26.4 months. No significant differences in PFS were observed on the basis of final doses of palbociclib (P = .77). Time to first dose reduction was 2.3 months. Median TTF was 26.1 months. Dose delays, reductions, and Grade 3/4 neutropenia were common (63%, n = 44; 57%, n = 40; and 62%, n = 43, respectively).

Conclusion: Real-world first-line palbociclib treatment produced outcomes similar to those in PALOMA-2 (Palbociclib and Letrozole in Advanced Breast Cancer) (median PFS 26.4 months vs. 24.8 months) despite more dose reductions (57%, n = 40 vs. 36%, n = 160) and shorter time to first dose reduction (2.3 vs. 3.0 months). No significant differences in PFS were observed for the varying palbociclib doses. Palbociclib dose reductions might not significantly affect PFS in the first-line setting.
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http://dx.doi.org/10.1016/j.clbc.2019.06.010DOI Listing
February 2020

Piperacillin/Tazobactam versus Tobramycin-Based Antibiotic Prophylaxis for Type III Open Fractures.

Surg Infect (Larchmt) 2020 Feb 5;21(1):23-28. Epub 2019 Aug 5.

Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Type III open fractures are associated with an infection rate as high as 50%. The optimal antibiotic for open fracture prophylaxis remains unclear, and the literature comparing the safety and efficacy of different antibiotic regimens is limited. The aim of this study was to compare the composite adverse events (AEs) in patients before and after a change in prophylactic antibiotic management for these injuries from a tobramycin- to a piperacillin/tazobactam-based regimen. This was a retrospective single-center cohort study of patients with Type III open fractures admitted from January 2010 to December 2016. Patients were included if they received either tobramycin plus cefazolin or clindamycin or piperacillin/tazobactam for fracture prophylaxis. The primary outcome was the rate of composite AEs, which included nephrotoxicity, surgical site infection (SSI), and hospital re-admission with surgical intervention. Secondary outcomes included the rate of SSI within 30 and 60 days after injury. Data were analyzed using the Student , Mann-Whitney U, and Fisher exact tests. Eighty-five patients were included. There were 29 events in the tobramycin group compared with three in the piperacillin/tazobactam group. At 30 days, SSI had occurred in 17 patients (27.5%) in the tobramycin group and 1 patient (4.3%) in the piperacillin/tazobactam group (p = 0.033). At 60 days, SSI had occurred in three additional patients in the tobramycin group (p = 0.009). There was no difference in the composite AEs in the piperacillin/tazobactam compared with the tobramycin group. However, SSI within 30 and 60 days was significantly more common with tobramycin.
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http://dx.doi.org/10.1089/sur.2019.064DOI Listing
February 2020

Pathological complete response rates with pertuzumab-based neoadjuvant chemotherapy in breast cancer: A single-center experience.

J Oncol Pharm Pract 2020 Apr 29;26(3):572-579. Epub 2019 Jun 29.

The Ohio State University Wexner Medical Center, Division of Medical Oncology, The Stefanie Spielman Comprehensive Breast Center, Columbus, OH, USA.

Background: Pertuzumab-based neoadjuvant chemotherapy (NAC) has demonstrated successful pathologic complete response (pCR) rates when administered to patients with human epidermal growth factor receptor 2 (HER2)-positive, locally advanced breast cancer and has become standard of care. This study aimed to identify pCR rates in patients receiving a variety of pertuzumab-based NAC regimens. The effect of the addition of an anthracycline and impact of anthracycline and taxane sequencing on pCR was also assessed.

Methods: A retrospective, single-center review was conducted on patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer that received one of five pertuzumab-containing NAC regimens followed by definitive surgery.

Results: Ninety-six patients were included in the analysis; overall, pCR was attained in 49 patients (51%). Of the 61 patients who received an anthracycline-containing NAC regimen, 30 (49%) attained a pCR. Of the 35 patients who received the non-anthracycline NAC regimen, 19 (54%) attained a pCR; difference in pCR was not statistically significant ( = 0.63). Anthracycline/taxane sequence analysis showed that of the patients attaining pCR with an anthracycline-containing NAC, 77% of patients received the taxane portion upfront ( = 0.17). Relative dose intensity of the anthracycline portion was similar irrespective of treatment sequence. However, relative dose intensity of the taxane portion was decreased with upfront anthracycline administration.

Conclusion: These findings support current recommendations of adding pertuzumab to established regimens for treatment of locally advanced, HER2-positive, early stage breast cancer. The benefit of adding an anthracycline in the neoadjuvant setting remains unclear. Patients treated with the taxane portion of NAC upfront appeared to have a higher rate of pCR and better relative dose intensity than patients who received the anthracycline portion upfront, but differences were not statistically significant. These findings should be verified in a prospective clinical trial.
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http://dx.doi.org/10.1177/1078155219857800DOI Listing
April 2020

Health care insecurity in the underserved: Effect of a charitable pharmacy model.

J Am Pharm Assoc (2003) 2019 Jul - Aug;59(4S):S19-S24. Epub 2019 May 9.

Objectives: The objectives of this study were to assess how a charitable pharmacy model affects patient perception of health care insecurity, physical and emotional functioning, and medication access in an underserved population.

Methods: New patients presenting for medication at their initial pharmacy visit at Charitable Pharmacy of Central Ohio were screened for eligibility during a 12-week enrollment period. Participants completed a baseline survey containing the Health Care Insecurity Measure (HCIM), Veterans RAND 12-Item Health Survey (VR-12), and medication access questions. The follow-up survey, which contained the HCIM and VR-12 only, was administered during a pharmacy visit at least 14 days after the patient's initial visit. Survey data were analyzed with the use of descriptive statistics.

Results: A total of 105 patients met eligibility criteria, and 17 patients declined to participate. Of the 88 remaining participants, 33 (38%) completed the study (both baseline and follow-up survey). Of the 33 participants who completed the study, there was a statistically significant decrease from the baseline health care insecurity score (23.2 ± 11.1) to the follow-up score (17.9 ± 8.5; P = 0.0031).

Conclusion: This study demonstrated that pharmacists working in a charitable pharmacy can have a positive impact on the sense of security patients feel about their health care and can better understand their medication-related needs.
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http://dx.doi.org/10.1016/j.japh.2019.03.011DOI Listing
August 2020

Tocilizumab as first-line therapy for steroid-refractory acute graft-versus-host-disease: analysis of a single-center experience.

Leuk Lymphoma 2019 09 15;60(9):2223-2229. Epub 2019 Feb 15.

Department of Pharmacy, The James Cancer Hospital, The Ohio State University Comprehensive Cancer Center , Columbus , Ohio , 43210 , USA.

Acute graft-versus-host-disease (aGVHD) is a complication after allogeneic stem cell transplant. After the failure of treatment with high dose corticosteroids, steroid-refractory aGVHD (SR aGVHD) is associated with high rates of mortality. Tocilizumab has evidence of activity in SR aGVHD. For patients ineligible for trials, the OSU James Comprehensive Cancer Center has been utilizing tocilizumab as first-line therapy for SR aGVHD. We retrospectively report on 15 patients who received tocilizumab. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 49 years. Median time to tocilizumab administration was 9 days (range, 3-16). Six patients had complete responses (40%) with a resolution of aGVHD. From the last contact, median overall survival for responders was not yet reached vs. 31 days for non-responders ( = .0002). Patients with skin and/or GI aGVHD demonstrated the greatest benefit. Patients with liver aGVHD did not respond. Future studies are needed to evaluate tocilizumab prior to steroid failure.
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http://dx.doi.org/10.1080/10428194.2019.1573996DOI Listing
September 2019

Impact of Paralytic Agent on Postintubation Sedation.

Air Med J 2019 Jan - Feb;38(1):39-44. Epub 2018 Oct 25.

Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH; Division of Pharmacy Practice and Science, The Ohio State University College of Pharmacy, Columbus, OH. Electronic address:

Objective: The aim of this study was to evaluate the difference in the time to postintubation sedation between patients receiving etomidate and either succinylcholine or rocuronium in the prehospital setting.

Setting: Patients who received rapid sequence intubation medications from transport service personnel and were subsequently intubated were included. The critical care transport agency operates 8 helicopter- and 3 ground-based emergency medical service units.

Methods: This retrospective cohort study compared the time to the first sedative in patients intubated with etomidate and succinylcholine versus etomidate and rocuronium. Enrollment of 64 patients per arm was needed to achieve 80% power with a 2-tailed alpha of 0.05.

Results: Sixty-four and 38 patients received succinylcholine or rocuronium, respectively. The median time to postetomidate sedation was 10 (range, 5.0-16.0) and 13.5 (range, 7.0-20.8) minutes for succinylcholine and rocuronium patients, respectively (P = .13). Given the average duration of effect of etomidate, succinylcholine, and rocuronium, 0 (0%) succinylcholine versus 33 (86.8%) rocuronium patients were found to be at risk of wakeful paralysis.

Conclusions: This study suggests rocuronium's long duration of effect puts patients at risk for wakeful paralysis once the short effects of etomidate have subsided.
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http://dx.doi.org/10.1016/j.amj.2018.09.006DOI Listing
April 2020

Microneedle-Based Delivery of Amphotericin B for Treatment of Cutaneous Leishmaniasis.

Biomed Microdevices 2019 01 7;21(1). Epub 2019 Jan 7.

Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Box 7115, Raleigh, NC, 27695-7115, USA.

Current therapeutic options against cutaneous leishmaniasis are plagued by several weaknesses. The effective topical delivery of an antileishmanial drug would be useful in treating some forms of cutaneous leishmaniasis. Toward this end, a microneedle based delivery approach for the antileishmanial drug amphotericin B was investigated in murine models of both New World (Leishmania mexicana) and Old World (Leishmania major) infection. In the L. mexicana model, ten days of treatment began on day 35 post infection, when the area of nodules averaged 9-15 mm. By the end of the experiment, a significant difference in nodule area was observed for all groups receiving topical amphotericin B at 25 mg/kg/day after application of microneedle arrays of 500, 750, and 1000 μM in nominal length compared to the group that received this dose of topical amphotericin B alone. In the L. major model, ten days of treatment began on day 21 post infection when nodule area averaged 51-65 mm in the groups. By the end of the experiment, there was no difference in nodule area between the group receiving 25 mg/kg of topical amphotericin B after microneedle application and any of the non-AmBisome groups. These results show the promise of topical delivery of amphotericin B via microneedles in treating relatively small nodules caused by L. mexicana. These data also show the limitations of the approach against a disseminated L. major infection. Further optimization of microneedle delivery is needed to fully exploit this strategy for cutaneous leishmaniasis treatment.
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http://dx.doi.org/10.1007/s10544-018-0355-8DOI Listing
January 2019

A Single Nucleotide Polymorphism in Was Associated With Clinical Response in Multiple Myeloma Patients.

Anticancer Res 2019 Jan;39(1):67-72

Deparment of Hematology & Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, U.S.A.

Background/aim: SLC7A5 is recognized as the major mediator of melphalan uptake into multiple myeloma (MM) cells; however, its contribution to the inter-patient variability of melphalan efficacy and toxicity is yet to be well elucidated. This study aimed to investigate the impact of a single nucleotide polymorphism (SNP) rs4240803 in SLC7A5 on the gene expression, ex vivo sensitivity to melphalan, and clinical outcomes in MM patients who were undergoing autologous stem cell transplantation with high-dose melphalan.

Materials And Methods: Peripheral blood mononuclear cells (PBMC) were collected from 108 MM patients prior to melphalan therapy. Clinical data were also collected from these patients following melphalan therapy.

Results: rs4240803 was associated with elevated expression of SLC7A5 mRNA, higher ex vivo sensitivity to melphalan in PBMCs, and positive 90-day response in these patients (p=0.047, 0.10, 0.049, respectively).

Conclusion: rs4240803 impacted the expression of SLC7A5, thus contributing to the clinical response of MM patients to melphalan therapy.
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http://dx.doi.org/10.21873/anticanres.13080DOI Listing
January 2019

Pharmacokinetic-Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High-Dose Melphalan for Autologous Stem Cell Transplant.

CPT Pharmacometrics Syst Pharmacol 2018 11 20;7(11):748-758. Epub 2018 Oct 20.

Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.

High-dose melphalan (HDM) is part of the conditioning regimen in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT). However, individual sensitivity to melphalan varies, and many patients experience severe toxicities. Prolonged severe neutropenia is one of the most severe toxicities and contributes to potentially life-threatening infections and failure of ASCT. Granulocyte-colony stimulating factor (G-CSF) is given to stimulate neutrophil proliferation after melphalan administration. The aim of this study was to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model capable of predicting neutrophil kinetics in individual patients with MM undergoing ASCT with high-dose melphalan and G-CSF administration. The extended PK/PD model incorporated several covariates, including G-CSF regimen, stem cell dose, hematocrit, sex, creatinine clearance, p53 fold change, and race. The resulting model explained portions of interindividual variability in melphalan exposure, therapeutic effect, and feedback regulation of G-CSF on neutrophils, thus enabling simulation of various doses and prediction of neutropenia duration.
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http://dx.doi.org/10.1002/psp4.12345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263666PMC
November 2018

Tolerance of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) Inhibitors in Patients With Self-Reported Statin Intolerance.

J Pharm Pract 2020 Jun 16;33(3):276-282. Epub 2018 Sep 16.

The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to lower atherogenic lipid markers in patients with statin intolerance; however, external validity of these findings is unclear in patients with self-reported statin intolerance.

Objective: The objective of this study was to describe the tolerability of evolocumab and alirocumab in patients with self-reported statin intolerance. Secondary objectives were to describe their efficacy and obtainability.

Methods: A retrospective chart review was completed and included adult patients with self-reported statin intolerance who were prescribed a PCSK9 inhibitor. Patient-reported side effects, laboratory values, and insurance information were collected for assessment of study objectives.

Results: During the study period, 55 patients were prescribed PCSK9 inhibitor, 42 started therapy, and 34 had at least 1 follow-up visit. While myalgias occurred in 14.7% (n = 5) of patients, flu-like symptoms in 11.8% (n = 4), and fatigue in 2.9% (n = 1), only 5.9% (n = 2) of prescriptions for PCSK9 inhibitors were discontinued. Low-density lipoprotein cholesterol (LDL-C) was reduced 48.7% (95% confidence interval [CI]: -1.7%-99.1%), and 20 (58.8%) patients achieved a ≥50% reduction in LDL-C. Regarding obtainability, of the 57 prescriptions written, 77.2% (n = 44) required prior authorization and 5.3% (n = 3) were denied by insurance.

Conclusion: PCSK9 inhibitors were well tolerated in patients with self-reported statin intolerance.
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http://dx.doi.org/10.1177/0897190018799218DOI Listing
June 2020
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