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result(s) for
"Larcher, Leon M."
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Systematic Screening of Commonly Used Commercial Transfection Reagents towards Efficient Transfection of Single-Stranded Oligonucleotides
by
Larcher, Leon M.
,
Veedu, Rakesh N.
,
Wang, Tao
in
cationic lipid
,
Cell Line
,
Cell Survival - drug effects
2018
Non-viral vector-mediated transfection is a core technique for in vitro screening of oligonucleotides. Despite the growing interests in the development of oliogonucleotide-based drug molecules in recent years, a comprehensive comparison of the transfection efficacy of commonly used commercial transfection reagents has not been reported. In this study, five commonly used transfection reagents, including Lipofectamine 3000, Lipofectamine 2000, Fugene, RNAiMAX and Lipofectin, were comprehensively analyzed in ten cell lines using a fluorescence imaging-based transfection assay. Although the transfection efficacy and toxicity of transfection reagents varied depending on cell types, the toxicity of transfection reagents generally displayed a positive correlation with their transfection efficacy. According to our results, Lipofectamine 3000, Fugene and RNAiMAX showed high transfection efficacy, however, RNAiMAX may be a better option for majority of cells when lower toxicity is desired. The transfection efficacy of Lipofectamine 2000 was compromised by its high toxicity, which may adversely affect its application in most cells. We firmly believe that our findings may contribute to the future In vitro delivery and screening of single-stranded therapeutic oligonucleotides such as antisense oligonucleotides, antimiRs, and DNAzymes.
Journal Article
Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics
2020
Exosomes are small extracellular vesicles with diameters of 30-150 nm. In both physiological and pathological conditions, nearly all types of cells can release exosomes, which play important roles in cell communication and epigenetic regulation by transporting crucial protein and genetic materials such as miRNA, mRNA, and DNA. Consequently, exosome-based disease diagnosis and therapeutic methods have been intensively investigated. However, as in any natural science field, the in-depth investigation of exosomes relies heavily on technological advances. Historically, the two main technical hindrances that have restricted the basic and applied researches of exosomes include, first, how to simplify the extraction and improve the yield of exosomes and, second, how to effectively distinguish exosomes from other extracellular vesicles, especially functional microvesicles. Over the past few decades, although a standardized exosome isolation method has still not become available, a number of techniques have been established through exploration of the biochemical and physicochemical features of exosomes. In this work, by comprehensively analyzing the progresses in exosome separation strategies, we provide a panoramic view of current exosome isolation techniques, providing perspectives toward the development of novel approaches for high-efficient exosome isolation from various types of biological matrices. In addition, from the perspective of exosome-based diagnosis and therapeutics, we emphasize the issue of quantitative exosome and microvesicle separation.
Journal Article
Adverse reactions of targeted therapy in cancer patients: a retrospective study of hospital medical data in China
by
Zhou, Huiyue
,
Larcher, Leon M.
,
Du, Ruofei
in
Adult
,
Adverse and side effects
,
Adverse reactions
2021
Background
The adverse reactions (ADRs) of targeted therapy were closely associated with treatment response, clinical outcome, quality of life (QoL) of patients with cancer. However, few studies presented the correlation between ADRs of targeted therapy and treatment effects among cancer patients. This study was to explore the characteristics of ADRs with targeted therapy and the prognosis of cancer patients based on the clinical data.
Methods
A retrospective secondary data analysis was conducted within an ADR data set including 2703 patients with targeted therapy from three Henan medical centers of China between January 2018 and December 2019. The significance was evaluated with chi-square test between groups with or without ADRs. Univariate and multivariate logistic regression with backward stepwise method were applied to assess the difference of pathological characteristics in patients with cancer. Using the univariate Cox regression method, the actuarial probability of overall survival was performed to compare the clinical outcomes between these two groups.
Results
A total of 485 patients were enrolled in this study. Of all patients, 61.0% (
n
= 296) occurred ADRs including skin damage, fatigue, mucosal damage, hypertension and gastrointestinal discomfort as the top 5 complications during the target therapy. And 62.1% of ADRs were mild to moderate, more than half of the ADRs occurred within one month, 68.6% ADRs lasted more than one month. Older patients (
P
= 0.022) and patients with lower education level (
P
= 0.036), more than 2 comorbidities (
P
= 0.021), longer medication time (
P
= 0.022), drug combination (
P
= 0.033) and intravenous administration (
P
= 0.019) were more likely to have ADRs. Those with ADRs were more likely to stop taking (
P
= 0.000), change (
P
= 0.000), adjust (
P
= 0.000), or not take the medicine on time (
P
= 0.000). The number of patients with recurrence (
P
= 0.000) and metastasis (
P
= 0.006) were statistically significant difference between ADRs and non-ADRs group. And the patients were significantly poor prognosis in ADRs groups compared with non-ADRs group.
Conclusion
The high incidence of ADRs would affect the treatment and prognosis of patients with cancer. We should pay more attention to these ADRs and develop effective management strategies.
Journal Article
Health-related quality of life and associated factors in patients with myocardial infarction after returning to work: a cross-sectional study
by
Wang, Panpan
,
Larcher, Leon M.
,
Wang, Tao
in
Analysis
,
Cardiac patients
,
Cardiovascular disease
2020
Background
Return to work following myocardial infarction (MI) represents an important indicator of recovery. However, MI can cause patients to feel pressure, loneliness and inferiority during work and even detachment from employment after returning to work, which may affect their quality of life. The aims of this study were to identify the influencing factors of Health-related quality of life (HRQoL) in patients with MI after returning to work and explore the correlations between these factors and HRQoL.
Method
This was a cross-sectional study. All participants were recruited from tertiary hospitals in China from October 2017 to March 2018. The general data questionnaire, Short-Form Health Survey-8 (SF-8), Health Promoting Lifestyle ProfileII (HPLPII), Medical Coping Modes Questionnaire (MCMQ) and Social Supporting Rating Scale (SSRS) were used to assess 326 patients with myocardial infarction returned to work after discharge. Multiple linear regression analysis was performed to explore factors related to HRQoL in patients with MI after returning to work.
Results
The sample consisted of 326 patients. The mean total score of quality of life was 28.03 ± 2.554. According to the multiple linear regression analysis, next factors were associated with better HRQoL: younger age (B = − 0.354,
P
= 0.039), higher income (B = 0.513,
P
= 0.000), less co-morbidity (B = − 0.440,
P
= 0.000), the longer time taken to return to work (B = 0.235,
P
= 0.003), fewer stents installed (B = − 0.359,
P
= 0.003), participation in cardiac rehabilitation (CR) (B = − 1.777,
P
= 0.000), complete CR (B = − 1.409,
P
= 0.000), better health behaviors such as more health responsibility (B = 0.172,
P
= 0.000) and exercise (B = 0.165,
P
= 0.000), better nutrition (B = 0.178,
P
= 0.000) and self-realization (B = 0.165,
P
= 0.000), stress response (B = 0.172,
P
= 0.000), more social support such as more objective support (B = 0.175,
P
= 0.000), subjective support (B = 0.167,
P
= 0.000) and better utilization of social support (B = 0.189,
P
= 0.028), positive copping strategies such as more coping (B = 0.133,
P
= 0.000) and less yield (B = − 0.165,
P
= 0.000).
Conclusions
HRQoL of MI patients after returning to work is not satisfactory. Health behavior, coping strategies, social support are factors which can affect HRQoL. A comprehensive and targeted guide may be a way to improve HRQoL and to assist patients’ successful return to society.
Journal Article
Development of Novel antimiRzymes for Targeted Inhibition of miR-21 Expression in Solid Cancer Cells
by
Larcher, Leon M.
,
Veedu, Rakesh N.
,
Wang, Tao
in
Antagomirs - chemistry
,
Antagomirs - genetics
,
antimiRzyme
2019
MicroRNAs (miRNAs) are short non-coding RNAs that are involved in the regulation of gene expression. Previous reports showed an over-expression of miRNA-21 (miR-21) in various cancer cells, and its up-regulation is closely related to cancer initiation, proliferation and metastasis. In this work, we envisioned the development of novel antimiRzymes (anti-miRNA-DNAzyme) that are capable of selectively targeting and cleaving miR-21 and inhibit its expression in cancer cells using the DNAzyme technique. For this purpose, we have designed different antimiRzyme candidates by systematically targeting different regions of miR-21. Our results demonstrated that RNV541, a potential arm-loop-arm type antimiRzyme, was very efficient (90%) to suppress miR-21 expression in U87MG malignant glioblastoma cell line at 200 nM concentration. In addition, RNV541 also inhibited miR-21 expression (50%) in MDA-MB-231 breast cancer cell line. For targeted delivery, we conjugated RNV541 with a transferrin receptor (TfR) targeting aptamer for TfR-mediated cancer cell delivery. As expected, the developed chimeric structure efficiently delivered the antimiRzyme RNV541 into TfR positive glioblastoma cells. TfR aptamer-RNV541 chimeric construct showed 52% inhibition of miR-21 expression in U87MG glioblastoma cells at 2000 nM concentration, without using any transfection reagents, making it a highly desirable strategy to tackle miR-21 over-expressed malignant cancers. Although these are in vitro based observations, based on our results, we firmly believe that our findings could be beneficial towards the development of targeted cancer therapeutics where conventional therapies face several challenges.
Journal Article
The health-related quality of life of lung cancer patients with EGFR-TKI-related skin adverse drug reactions and its relationship with coping style and self-management
2022
Purpose
The status and associated factors of the health-related quality of life of non-small-cell lung cancer (NSCLC) patients under targeted anti-cancer therapy have not been investigated. Self-management and coping style have been proven to be closely related to patients’ health-related quality of life. Based on these observations, this study was designed to firstly assess the status of health-related quality of life, and then explore the relationships among coping styles, self-management, and health-related quality of life of NSCLC patients with skin adverse drug reactions under targeted therapy.
Methods
We performed a cross-sectional study including 536 NSCLC patients with skin adverse drug reactions under targeted therapy in cancer clinics of three hospitals in China between May 2020 and May 2021. Structured questionnaires, including the Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitor 18, Cancer Patient Self-management Evaluation Scale, and Medical Coping Modes Questionnaire, were used to collect data. Relationships among coping style, self-management, and health-related quality of life were identified by Pearson correlation analysis and a multiple linear regression algorithm.
Results
The total score of health-related quality of life was 46 ± 12.84 in 536 NSCLC patients with skin adverse drug reactions undergoing targeted therapy. Health-related quality of life was positively correlated with self-management (
r
= 0.785,
P
< 0.01) and facing (
r
= 0.807,
P
< 0.01) and negatively correlated with yield (
r
= − 0.718,
P
< 0.01), avoidance (
r
= − 0.711,
P
< 0.01), and the severity of skin adverse reactions (
r
= − 0.722,
P
= 0.000). Via multiple linear regression analysis, we identified some significant factors associated with health-related quality of life, including age, education level, combination of medicine, Charlson Comorbidity Index, stages of disease, facing, yield, symptom management, daily activity management, psychological and emotional management, self-efficacy, and self-management (
P
< 0.05).
Conclusions
NSCLC patients with skin adverse drug reactions undergoing targeted therapy generally had a compromised health-related quality of life. The critical factors that were associated with the status of health-related quality of life were age, education level, comorbidity, the combinatorial application of drugs, stage of disease, self-management, and coping styles.
Journal Article
Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies
by
Larcher, Leon M.
,
Veedu, Rakesh N.
,
Balachandran, Akilandeswari A.
in
Biosynthesis
,
Brain cancer
,
Brain tumors
2020
Brain cancer is one among the rare cancers with high mortality rate that affects both children and adults. The most aggressive form of primary brain tumor is glioblastoma. Secondary brain tumors most commonly metastasize from primary cancers of lung, breast, or melanoma. The five-year survival of primary and secondary brain tumors is 34% and 2.4%, respectively. Owing to poor prognosis, tumor heterogeneity, increased tumor relapse, and resistance to therapies, brain cancers have high mortality and poor survival rates compared to other cancers. Early diagnosis, effective targeted treatments, and improved prognosis have the potential to increase the survival rate of patients with primary and secondary brain malignancies. MicroRNAs (miRNAs) are short noncoding RNAs of approximately 18–22 nucleotides that play a significant role in the regulation of multiple genes. With growing interest in the development of miRNA-based therapeutics, it is crucial to understand the differential role of these miRNAs in the given cancer scenario. This review focuses on the differential expression of ten miRNAs (miR-145, miR-31, miR-451, miR-19a, miR-143, miR-125b, miR-328, miR-210, miR-146a, and miR-126) in glioblastoma and brain metastasis. These miRNAs are highly dysregulated in both primary and metastatic brain tumors, which necessitates a better understanding of their role in these cancers. In the context of the tumor microenvironment and the expression of different genes, these miRNAs possess both oncogenic and/or tumor-suppressive roles within the same cancer.
Journal Article
Health-related quality of life and associated factors in patients with myocardial infarction after returning to work: a cross-sectional study
2020
Return to work following myocardial infarction (MI) represents an important indicator of recovery. However, MI can cause patients to feel pressure, loneliness and inferiority during work and even detachment from employment after returning to work, which may affect their quality of life. The aims of this study were to identify the influencing factors of Health-related quality of life (HRQoL) in patients with MI after returning to work and explore the correlations between these factors and HRQoL. This was a cross-sectional study. All participants were recruited from tertiary hospitals in China from October 2017 to March 2018. The general data questionnaire, Short-Form Health Survey-8 (SF-8), Health Promoting Lifestyle ProfileII (HPLPII), Medical Coping Modes Questionnaire (MCMQ) and Social Supporting Rating Scale (SSRS) were used to assess 326 patients with myocardial infarction returned to work after discharge. Multiple linear regression analysis was performed to explore factors related to HRQoL in patients with MI after returning to work. The sample consisted of 326 patients. The mean total score of quality of life was 28.03 [+ or -] 2.554. According to the multiple linear regression analysis, next factors were associated with better HRQoL: younger age (B = - 0.354, P = 0.039), higher income (B = 0.513, P = 0.000), less co-morbidity (B = - 0.440, P = 0.000), the longer time taken to return to work (B = 0.235, P = 0.003), fewer stents installed (B = - 0.359, P = 0.003), participation in cardiac rehabilitation (CR) (B = - 1.777, P = 0.000), complete CR (B = - 1.409, P = 0.000), better health behaviors such as more health responsibility (B = 0.172, P = 0.000) and exercise (B = 0.165, P = 0.000), better nutrition (B = 0.178, P = 0.000) and self-realization (B = 0.165, P = 0.000), stress response (B = 0.172, P = 0.000), more social support such as more objective support (B = 0.175, P = 0.000), subjective support (B = 0.167, P = 0.000) and better utilization of social support (B = 0.189, P = 0.028), positive copping strategies such as more coping (B = 0.133, P = 0.000) and less yield (B = - 0.165, P = 0.000). HRQoL of MI patients after returning to work is not satisfactory. Health behavior, coping strategies, social support are factors which can affect HRQoL. A comprehensive and targeted guide may be a way to improve HRQoL and to assist patients' successful return to society.
Journal Article
Adverse Reactions of Targeted Therapy in Cancer Patients: A Retrospective Study of Hospital Medical Data in China
2020
Background: The adverse reactions (ADR) of targeted therapy were closely related to the treatment efficacy, quality of life (QoL) and prognosis of cancer patients. However, few studies analyzed the ADR of targeted therapy and their effects on cancer patients. This study was conducted to describe the incidence and characteristics of ADR in cancer patients with targeted therapy and outcomes associated with ADR based on hospital medical data. Methods: A retrospective secondary data analysis was conducted using ADR data in hospital medical record collected from a cohort (n=2,703 with targeted therapy) in three hospitals of Henan, China from January 2018 to December 2019. The type, classification, occurrence time and duration of ADR, medication compliance and drug application, QoL, disease progress and survival of patients were analyzed. Results: A total of 485 patients met the inclusion criteria. 296 (61.0%) patients had ADR during target therapy. The top five ADR in this study were damage to skin, fatigue, mucosal damage, hypertension and gastrointestinal discomfort. 62.1% of the ADR were mild to moderate, more than half of the ADR occurred within one month, 68.6% ADR lasted more than one month. Older patients (P=0.022) and patients with lower education level (P=0.036), more than 2 comorbidities (P=0.021), longer medication time (P=0.022), drug combination (P=0.033) and intravenous administration (P=0.019) were more likely to have ADR. Those who had ADR were more likely to stop taking (P=0.025), change (P=0.010), adjust (P=0.019), or not take the medicine on time (P=0.022), or undergo cancer recurrence (P=0.027) and show higher rates of metastasis (P=0.009) . Conclusion: The incidence of ADR in cancer patients during targeted therapy was high. Age, education level, comorbidity and medication strategy can affect ADR. Furthermore, ADR would affect the treatment and prognosis of patients. We should pay more attention to these ADRs and develop effective management strategies.
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