25 research outputs found

    Screening of GPCR drugs for repurposing in breast cancer

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    Drug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to identify drugs with repurposing potential. In this study, we evaluated GPCR-targeting drugs by high throughput screening (HTS) for their repurposing potential in triple-negative breast cancer (TNBC) and drug-resistant human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC), due to the dire need to discover novel targets and drugs in these subtypes. We assessed the efficacy and potency of drugs/compounds targeting different GPCRs for the growth rate inhibition in the following models: two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and two HER2+ BC cell lines (BT474 and SKBR3), sensitive or resistant to lapatinib + trastuzumab, an effective combination of HER2-targeting therapies. We identified six drugs/compounds as potential hits, of which 4 were FDA-approved drugs. We focused on β-adrenergic receptor-targeting nebivolol as a candidate, primarily because of the potential role of these receptors in BC and its excellent long-term safety profile. The effects of nebivolol were validated in an independent assay in all the cell line models. The effects of nebivolol were independent of its activation of β3 receptors and nitric oxide production. Nebivolol reduced invasion and migration potentials which also suggests its inhibitory role in metastasis. Analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset found numerically but not statistically significant reduced risk of all-cause mortality in the nebivolol group. In-depth future analyses, including detailed in vivo studies and real-world data analysis with more patients, are needed to further investigate the potential of nebivolol as a repurposed therapy for BC

    Vertigo in a district NHS hospital

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    A naturalistic observation study of medication counseling practices at retail chain pharmacies

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    Objective: This study evaluated medication counseling procedures and trends at retail pharmacies in the Houston metropolitan area through a naturalistic observational study. Methods: A blinded cross-sectional observational study was conducted at retail pharmacies in the Houston metropolitan area. Data were collected by trained observers utilizing an observational log, to record various parameters that could have an impact on the duration of patient-pharmacist interaction in a naturalistic pharmacy practice setting. Additionally, indicators of counseling such as utilization of the counseling window and performance of show-and-tell were recorded. Statistical analyses included descriptive statistics, t-tests, Pearson correlations, ANOVAs, and multiple linear regressions. Results: One hundred and sixty-five interactions between patients and pharmacy staff were recorded at 45 retail pharmacies from 7 retail pharmacy chains. The counseling window was utilized in only 3 (1.81%) out of 165 observations and the show-and-tell process was observed in just 1(0.61%) interaction during this study. Mean (SD) interaction time between patient and pharmacists [159.50 (84.50)] was not statistically different (p>0.05) from the mean interaction time between patients and pharmacy technicians [139.30 (74.19)], irrespective of type of the retail chain observed. However, it was influenced by the number of patients waiting in queue. Patient wait time significantly differed by the time of the day the interaction was observed, weekends and weekdays had significantly different wait times and patient interaction times Multiple linear regression analyses indicated that, patient interaction time, pharmacy chain type, initial contact (pharmacist/technician), and time of the day, were significantly associated with patient wait time whereas patient wait time, pharmacy chain type, number of patients in queue, and number of pharmacy technician were significantly associated with interaction time. Conclusions: Our study found that the key indicators of counseling including the use of the counseling window and the show-and-tell process were absent, suggesting lack of adequate pharmacists counseling. Further studies are needed to evaluate the validity of this conclusion and the role of pharmacy services and its value towards medication use and safety

    Fertility and sexuality in the spinal cord injury patient

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    BACKGROUND: After a spinal cord injury, patients have different perceptions of sexuality, sexual function, and potential for fertility. These changes can greatly impact quality of life over a lifetime. PURPOSE: The purpose of this workgroup was to identify common evidence based or expert opinion themes and recommendations regarding treatment of sexuality, sexual function and fertility in the spinal cord injury population. METHODS: As part of the SIU-ICUD joint consultation of Urologic Management of the Spinal Cord Injury (SCI), a workgroup and comprehensive literature search of English language manuscripts regarding fertility and sexuality in the spinal cord injury patient were formed. Articles were compiled, and recommendations in the chapter are based on group discussion and follow the Oxford Centre for Evidence-based Medicine system for levels of evidence (LOEs) and grades of recommendation (GORs). RESULTS: Genital arousal, ejaculation, and orgasm are significantly impacted after spinal cord injury in both male and female SCI patients. This may have a more significant impact on potential for fertility in male spinal cord injury patients, particularly regarding ability of generate erection, semen quantity and quality. Female patients should be consulted that pregnancy is still possible after injury and a woman should expect resumption of normal reproductive function. As a result, sexual health teaching should be continued in women despite injury. Pregnancy in a SCI may cause complications such as autonomic dysreflexia, so this group should be carefully followed during pregnancy. CONCLUSIONS: By understanding physiologic changes after injury, patients and care teams can work together to achieve goals and maximize sexual quality of life after the injury.status: publishe

    Neurogenic bowel management for the adult spinal cord injury patient

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    BACKGROUND: Bowel function can be markedly changed after a spinal cord injury (SCI). These changes, and the care associated with managing the changes, can greatly impact a person's quality of life over a lifetime. PURPOSE: The purpose of the SIU-ICUD workgroup was to identify, assess, and summarize evidence and expert opinion-based themes and recommendations regarding bowel function and management in SCI populations. METHODS: As part of the SIU-ICUD joint consultation of Urologic Management of the Spinal Cord Injury, a workgroup was formed and comprehensive literature search of English language manuscripts regarding bowel physiology and management plans for the SCI patient. Articles were compiled, and recommendations in the chapter are based on group discussion and follow the Oxford Centre for Evidence-based Medicine system for levels of evidence (LOEs) and grades of recommendation (GORs). RESULTS: Neurogenic bowel symptoms are highly prevalent in the SCI population. Patients with injuries above the conus medullaris have increased bowel motility and poor anorectal sphincter relaxation. Patients with injuries below the conus are more likely to have an areflexic colon and low sphincter tone. Conservative management strategies include diet modification and anorectal stimulation. There are few evidence-based pharmacologic interventions, which improve fecal transit time. Intestinal ostomy can be an effective treatment for reducing hours spent per week on bowel management and colostomy may be easier to manage than ileostomy due to solid vs liquid stool. CONCLUSIONS: By understanding physiology and treatment options, patients and care teams can work together to achieve goals and maximize quality of life after injury.status: publishe

    Table3_Screening of GPCR drugs for repurposing in breast cancer.XLSX

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    Drug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to identify drugs with repurposing potential. In this study, we evaluated GPCR-targeting drugs by high throughput screening (HTS) for their repurposing potential in triple-negative breast cancer (TNBC) and drug-resistant human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC), due to the dire need to discover novel targets and drugs in these subtypes. We assessed the efficacy and potency of drugs/compounds targeting different GPCRs for the growth rate inhibition in the following models: two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and two HER2+ BC cell lines (BT474 and SKBR3), sensitive or resistant to lapatinib + trastuzumab, an effective combination of HER2-targeting therapies. We identified six drugs/compounds as potential hits, of which 4 were FDA-approved drugs. We focused on β-adrenergic receptor-targeting nebivolol as a candidate, primarily because of the potential role of these receptors in BC and its excellent long-term safety profile. The effects of nebivolol were validated in an independent assay in all the cell line models. The effects of nebivolol were independent of its activation of β3 receptors and nitric oxide production. Nebivolol reduced invasion and migration potentials which also suggests its inhibitory role in metastasis. Analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset found numerically but not statistically significant reduced risk of all-cause mortality in the nebivolol group. In-depth future analyses, including detailed in vivo studies and real-world data analysis with more patients, are needed to further investigate the potential of nebivolol as a repurposed therapy for BC.</p

    DataSheet2_Screening of GPCR drugs for repurposing in breast cancer.PDF

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    Drug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to identify drugs with repurposing potential. In this study, we evaluated GPCR-targeting drugs by high throughput screening (HTS) for their repurposing potential in triple-negative breast cancer (TNBC) and drug-resistant human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC), due to the dire need to discover novel targets and drugs in these subtypes. We assessed the efficacy and potency of drugs/compounds targeting different GPCRs for the growth rate inhibition in the following models: two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and two HER2+ BC cell lines (BT474 and SKBR3), sensitive or resistant to lapatinib + trastuzumab, an effective combination of HER2-targeting therapies. We identified six drugs/compounds as potential hits, of which 4 were FDA-approved drugs. We focused on β-adrenergic receptor-targeting nebivolol as a candidate, primarily because of the potential role of these receptors in BC and its excellent long-term safety profile. The effects of nebivolol were validated in an independent assay in all the cell line models. The effects of nebivolol were independent of its activation of β3 receptors and nitric oxide production. Nebivolol reduced invasion and migration potentials which also suggests its inhibitory role in metastasis. Analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset found numerically but not statistically significant reduced risk of all-cause mortality in the nebivolol group. In-depth future analyses, including detailed in vivo studies and real-world data analysis with more patients, are needed to further investigate the potential of nebivolol as a repurposed therapy for BC.</p
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