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Article ; Online: An Unusual Case of Hepatocellular Carcinoma in a Healthy Teenager.

Ugonabo, Onyinye / Pulipati, Yochita / Elghezewi, Adnan / Miller, Virginia / Logan, Lawrence / Pramod, Pantangi

Journal of investigative medicine high impact case reports

2023 Volume 11, Page(s) 23247096231165744

Abstract: Hepatocellular carcinoma (HCC) is a primary liver malignancy known to occur majorly in patients with liver cirrhosis or those with a harbinger of risk factors like viral hepatitis, autoimmune liver disease, alpha-1 antitrypsin deficiency, alcoholic liver ...

Abstract	Hepatocellular carcinoma (HCC) is a primary liver malignancy known to occur majorly in patients with liver cirrhosis or those with a harbinger of risk factors like viral hepatitis, autoimmune liver disease, alpha-1 antitrypsin deficiency, alcoholic liver disease, and nonalcoholic fatty liver disease. The incidence of HCC has risen in the past 2 decades and currently ranks as the sixth most common cause of cancer-related death worldwide. Most cases are seen in adulthood, and only a very small percentage have been reported in adolescents with risk factors. The 2 pathologic subtypes of pediatric HCC are classic and fibrolamellar. Here, we discussed a very interesting rare case of a healthy male teenager with no apparent liver disease or risk factor who presented with right-upper-quadrant pain, normal alpha-fetoprotein level, and abdominal ultrasound showing a large hepatic mass. A liver biopsy was positive for HCC with fluorescent in situ hybridization showing a PRKACA complex gene pattern, favoring the fibrolamellar type.
MeSH term(s)	Child ; Humans ; Male ; Adolescent ; Carcinoma, Hepatocellular/etiology ; Carcinoma, Hepatocellular/genetics ; Liver Neoplasms/pathology ; In Situ Hybridization, Fluorescence ; Liver Cirrhosis/complications
Language	English
Publishing date	2023-05-21
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2710326-2
ISSN	2324-7096 ; 2324-7096
ISSN (online)	2324-7096
ISSN	2324-7096
DOI	10.1177/23247096231165744
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cardiac Glycosides Increase Temozolomide Anticancer Activity in Therapy Resistant Glioblastoma Cells

Anisha Valluri / Logan Lawrence / Krista L. Denning / Jonathan Cuda / Guo-Zhang Zhu

International Journal of Translational Medicine, Vol 2, Iss 12, Pp 148-

2022 Volume 155

Abstract: Glioblastomas (GBMs) are a form of malignant gliomas characterized by a dismal prognosis. Standard treatment for glioblastoma patients is combined maximal surgical removal of the tumor with postoperative radiotherapy and concomitant chemotherapy with ... ...

Abstract	Glioblastomas (GBMs) are a form of malignant gliomas characterized by a dismal prognosis. Standard treatment for glioblastoma patients is combined maximal surgical removal of the tumor with postoperative radiotherapy and concomitant chemotherapy with Temozolomide (TMZ). Among the histological characteristics that contribute to GBM progression are the rapid proliferation and neo-angiogenetic processes. The Na + /K + -ATPase is a transporter that promotes the migration of cancer cells, and its aberrant expression and activity have been associated with several cancers, including GBM. Using cardiac glycosides, we examined the effects of direct inhibition of the Na + /K + -ATPase in glioblastoma cells in vitro. We found that cardiac glycoside Digoxin is an effective anticancer agent on several glioma cell lines via Na + /K + -ATPase inhibition. Drug cytotoxicity assays showed that Digoxin as monotherapy significantly increased cell death and increased the efficacy of Temozolomide (TMZ) in the glioma cell lines T98G, U-97 MG, and primary GBM cells BNC-6. Additionally, Digoxin exhibited important anti-migratory effects on the highly aggressive and chemotherapy-resistant T98G glioma cell-line, demonstrating a potential therapeutic role for cardiac glycosides.
Keywords	glioblastoma ; anticancer activity ; cardiac glycosides ; combination therapy ; digoxin ; sodium/potassium pump ; Computer applications to medicine. Medical informatics ; R858-859.7
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Non-selective Primary Human Tumor Cell Line Generation from Surgical Resections to be Paired With Flash Frozen and Paraffin Embedded Tissue

Jennifer Hawkins / Rebecca Russell / Logan Lawrence / Amrita Valluri / Jessica Wellman / Krista Denning

Marshall Journal of Medicine, Vol 7, Iss 2, p

Advancements in Democratizing Translational Research Materials to Rural Institutions

2021 Volume 27

Abstract: Translational cancer research relies on the availability of human patient tissue demonstrating the specific disease process under investigation. Biobanks of human tissue have historically been and remain to date the primary access point for cancer ... ...

Abstract	Translational cancer research relies on the availability of human patient tissue demonstrating the specific disease process under investigation. Biobanks of human tissue have historically been and remain to date the primary access point for cancer research samples. Biorepositories routinely supply researchers with varying sample types for use in biomedical studies; most commonly formalin-fixed and paraffin-embedded (FFPE) tissue, or fresh snap-frozen tissue. In conjunction with preserved tissue samples, viable tumor cell lines derived from patient tissue have emerged to be a new gold standard in cancer research particularly in drug discovery and functional prognostic assays. Tissue banks providing these samples are being termed “next-generation” and are adapting to directly assist researchers by performing high throughput technical studies such as routine histology and immunostaining of donor tissue. These high quality, next-generation biorepositories are a relatively scarce resource in the broader research community in the United States and have traditionally been associated with large centralized and very well established university medical centers. This article describes the next-generation resources now available at the Edwards Comprehensive Cancer Center with its association with the Marshall University Joan C. Edwards School of Medicine in Huntington, West Virginia. This manuscript details the procedures, protocols, and success rates of the Tissue Procurement Program (TPP) to generate a growing cohort of viable primary human tumor cell lines representing varying malignancies to be used in conjunction with matched formalin-fixed and paraffin-embedded (FFPE) and snap-frozen tissue samples for comprehensive translational research.
Keywords	translational research ; biobanking ; cancer research ; human tissue ; biorepository ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Marshall University
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Children, young people and parent engagement in health intervention design and implementation

Daniel Crowther / Holly McCulloch / Helen Wong / Rebecca Mackay / Catie Johnson / Jill Chorney / Krista Ritchie / Logan Lawrence / Andrea Bishop / Melissa Helwig / Janet Curran

Health Expectations, Vol 26, Iss 1, Pp 1-

A scoping review

2023 Volume 15

Abstract: Abstract Introduction Engaging children and young people (CYP) with and without their parents in health research has the potential to improve the development and implementation of health interventions. However, to our knowledge, the scope of engagement ... ...

Abstract	Abstract Introduction Engaging children and young people (CYP) with and without their parents in health research has the potential to improve the development and implementation of health interventions. However, to our knowledge, the scope of engagement activities used with this population and barriers to their engagement is unknown. The objective of this review was to identify and describe CYP engagement with and without their parents in the development and/or implementation of health interventions. Methods This scoping review included any primary research studies reporting on engaging CYP, with or without parents, in the design and/or implementation of health interventions. Healthcare professionals had to be involved over the course of the study and the study had to take place in either community, primary or tertiary care settings. The following databases were searched in May 2017, May 2020 and June 2021: Medline (OVID), CINAHL (EBSCO) and Embase (Elsevier). Two independent reviewers screened titles, abstracts and full‐text articles and used a previously piloted extraction form to extract and summarize information from the included articles. Results Twenty‐eight articles discussing twenty‐four studies were included. CYP engagement throughout the research cycle was limited. There were no observed differences in the reported presence of engagement, types of interventions or outcomes of engagement between studies engaging CYP or CYP and parents. Studies engaging CYP and parents contained limited information on how these relationships affected outcomes of engagement. Engagement was enabled primarily by the maintenance of resources and relationships among stakeholders. Conclusions Although CYP engagement often influenced health intervention and implementation design, they are inconsistently engaged across the research cycle. It is unclear whether parental involvement enhances CYP engagement. Future research should consider reporting guidelines to clarify the level of CYP and/or parent engagement, and enhance CYP ...
Keywords	children ; engagement ; health interventions ; parent ; young people ; Medicine (General) ; R5-920 ; Public aspects of medicine ; RA1-1270
Subject code	360
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: mTOR Regulation of N-Myc Downstream Regulated 1 (NDRG1) Phosphorylation in Clear Cell Renal Cell Carcinoma

Anisha Valluri / Jessica Wellman / Chelsea L. McCallister / Kathleen C. Brown / Logan Lawrence / Rebecca Russell / James Jensen / James Denvir / Monica A. Valentovic / Krista L. Denning / Travis B. Salisbury

International Journal of Molecular Sciences, Vol 24, Iss 9364, p

2023 Volume 9364

Abstract: The mechanistic target of rapamycin (mTOR) kinase is a component of two signaling complexes that are known as mTOR complex 1 (mTORC1) and mTORC2. We sought to identify mTOR-phosphorylated proteins that are differently expressed in clinically resected ... ...

Abstract	The mechanistic target of rapamycin (mTOR) kinase is a component of two signaling complexes that are known as mTOR complex 1 (mTORC1) and mTORC2. We sought to identify mTOR-phosphorylated proteins that are differently expressed in clinically resected clear cell renal cell carcinoma (ccRCC) relative to pair-matched normal renal tissue. Using a proteomic array, we found N-Myc Downstream Regulated 1 (NDRG1) showed the greatest increase (3.3-fold) in phosphorylation (on Thr346) in ccRCC. This was associated with an increase in total NDRG1. RICTOR is a required subunit in mTORC2, and its knockdown decreased total and phospho-NDRG1 (Thr346) but not NDRG1 mRNA. The dual mTORC1/2 inhibitor, Torin 2, significantly reduced (by ~100%) phospho-NDRG1 (Thr346). Rapamycin is a selective mTORC1 inhibitor that had no effect on the levels of total NDRG1 or phospho-NDRG1 (Thr346). The reduction in phospho-NDRG1 (Thr346) due to the inhibition of mTORC2 corresponded with a decrease in the percentage of live cells, which was correlated with an increase in apoptosis. Rapamycin had no effect on ccRCC cell viability. Collectively, these data show that mTORC2 mediates the phosphorylation of NDRG1 (Thr346) in ccRCC. We hypothesize that RICTOR and mTORC2-mediated phosphorylation of NDRG1 (Thr346) promotes the viability of ccRCC cells.
Keywords	N-Myc Downstream Regulated 1 ; NDRG1 ; clear cell renal cell carcinoma ; mTOR ; mTORC1 ; mTORC2 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The application of implementation science theories for population health

Jessie-Lee McIsaac / Grace Warner / Logan Lawrence / Robin Urquhart / Sheri Price / Jacqueline Gahagan / Mary McNally / Lois A Jackson

AIMS Public Health, Vol 5, Iss 1, Pp 13-

A critical interpretive synthesis

2018 Volume 30

Abstract: Background and Purpose: Over the last decade, the field of implementation science (IS) has yielded an array of theoretical approaches to clarify and understand how factors influence the application and scaling-up of evidence-based practice in health care. ...

Abstract	Background and Purpose: Over the last decade, the field of implementation science (IS) has yielded an array of theoretical approaches to clarify and understand how factors influence the application and scaling-up of evidence-based practice in health care. These developments have led to questions about whether IS theories and frameworks might be of value to population health researchers and decision makers. The purpose of this research was to conduct a critical interpretive synthesis to explore, if, and how, key IS theories and frameworks might inform population health interventions aimed at reducing the burden of illness across populations. Methods: An initial list of theories and frameworks was developed based on previous published research and narrowed to focus on theories considered as formative for the field of IS. A standardized data extraction form was used to gather key features of the theories and critically appraise their relevance to population health interventions. Results: Ten theories were included in the review and six deemed most applicable to population health based on their consideration of broader contextual and system-level factors. The remaining four were determined to have less relevant components for population health due to their limited consideration of macro-level factors, often focusing on micro (individual) and meso (organizational) level factors. Conclusions: Theories and frameworks are important to guide the implementation and sustainability of population health interventions. The articulation of meso level factors common in IS theories may be of value to interventions targeted at the population level. However, some of the reviewed theories were limited in their consideration of broader contextual factors at the macro level (community, policy or societal). This critical interpretive synthesis also found that some theories lacked provision of practical guidance to address interventions targeting structural factors such as key social determinants of health (e.g., housing, income).
Keywords	implementation science ; population health ; theory ; framework ; critical review ; Public aspects of medicine ; RA1-1270
Subject code	360
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	AIMS Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Physical activity in persons with Parkinson disease

C. Allyson Jones / Marguerite Wieler / Jennifer Carvajal / Logan Lawrence / Robert Haennel

Health, Vol 04, Iss 11, Pp 1145-

A feasibility study

2012 Volume 1152

Abstract: Background: Physical activity for persons with Parkinson Disease (PD) is recommended yet little is known about the physical activity levels in this patient population. The primary aim was to assess the feasibility of using a direct measurement and self- ... ...

Abstract	Background: Physical activity for persons with Parkinson Disease (PD) is recommended yet little is known about the physical activity levels in this patient population. The primary aim was to assess the feasibility of using a direct measurement and self-report measure of physical activity in patients with PD. Methods: Physical activity was recorded in 11 out-patients with mild to moderate PD. An accelerometer based sensor system (SenseWear Pro Armband?) which was worn continuously over 2 days was used to measure physical activity. Minute by minute energy expenditure and steps per day were recorded. Self-report physical activity was measured using the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH) which assessed average weekly activity. Results: Using the accelerometer based sensor system, 83% of the day was spent in sedentary activity with the majority active time spent at a light intensity (2.7 [SD 2.0] hrs/day). Self-reported mean number of hours for activities greater than 2.0 METs was 3.4 (SD 1.5) hrs/day. Although the overall time spent in activity did not differ between the accelerometer and SQUASH, partici- pants reported a higher proportion of activities at the moderate and vigorous intensities than the accelerometer recorded. Conclusions: Measurement of physical activity is a challenge in persons with PD given the disease-related symptoms. We found that, by all accounts, a self-report measure of physical activity should be complemented with a direct measure of physical activity.
Keywords	Parkinson Disease ; Physical Activity ; Quality of Life ; Exercise Test ; Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	796
Language	English
Publishing date	2012-11-01T00:00:00Z
Publisher	Scientific Research Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Chemo-predictive assay for targeting cancer stem-like cells in patients affected by brain tumors.

Sarah E Mathis / Anthony Alberico / Rounak Nande / Walter Neto / Logan Lawrence / Danielle R McCallister / James Denvir / Gerrit A Kimmey / Mark Mogul / Gerard Oakley / Krista L Denning / Thomas Dougherty / Jagan V Valluri / Pier Paolo Claudio

PLoS ONE, Vol 9, Iss 8, p e

2014 Volume 105710

Abstract: Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs) resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that ... ...

Abstract	Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs) resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID), which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents. Two patients, a 21-year old male (patient 1) and a 5-month female (patient 2), affected by anaplastic WHO grade-III ependymoma were screened using the ChemoID assay. Patient 1 was found sensitive to the combination of irinotecan and bevacizumab, which resulted in a prolonged disease progression free period of 18 months. Following recurrence, the combination of various chemotherapy drugs was tested again with the ChemoID assay. We found that benzyl isothiocyanate (BITC) greatly increased the chemosensitivity of the ependymoma cells to the combination of irinotecan and bevacizumab. After patient 1 was treated for two months with irinotecan, bevacizumab and supplements of cruciferous vegetable extracts containing BITC, we observed over 50% tumoral regression in comparison with pre-ChemoID scan as evidenced by MRI. Patient 2 was found resistant to all treatments tested and following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, the tumor of this patient rapidly progressed and proton beam therapy was recommended. As expected animal studies conducted with patient derived xenografts treated with ChemoID screened drugs recapitulated the clinical observation. This assay demonstrates that patients with the same histological stage and grade of cancer may vary considerably in their clinical response, suggesting that ChemoID testing which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents could lead to more effective and personalized anticancer treatments in the future.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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