Δευτέρα 4 Ιανουαρίου 2021

Pancreatic adenocarcinoma: molecular drivers and the role of targeted therapy

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Abstract

Prognosis from pancreatic ductal adenocarcinoma (PDAC) continues to be poor despite the many efforts channeled to improve its management. Although the mainstay treatment is still traditional chemotherapy, recent advances highlighted a promising potential for targeted therapy in the management of this disease. Those advances emphasize the significance of timely genomic profiling of tumor tissue as well as germline testing of patients to identify potential markers of targeted therapy. While targeted therapy is reserved for a relatively small subset of patients with PDAC, ongoing research is uncovering additional markers, and targeted agents, that will hopefully translate to better outcomes for patients.

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Characterization of primary glioma cell lines derived from the patients according to 2016 CNS tumour WHO classification and comparison with their parental tumours

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Abstract

Background

Gliomas represent about 80% of primary brain tumours and about 30% of malignant ones, which today don't have a resolution therapy because of their variability. A valid model for the study of new personalized therapies can be represented by primary cultures from patient's tumour biopsies.

Methods

In this study we consider 12 novel cell lines established from patients' gliomas and immunohistochemically and molecularly characterized according to the newly updated 2016 CNS Tumour WHO classification.

Results

Eight of these lines were glioblastoma cells, two grade III glioma cells (anaplastic astrocytoma and oligo astrocytoma) and two low grade glioma cells (grade II astrocytoma and oligodendroglioma). All cell lines were analysed by immunohistochemistry for specific glioma markers, respectively VIMENTIN, GFAP, IDH1R132, and ATRX. The methylation status of the MGMT gene promoter was also determined in all lines. The comparison of the immunohistochemical characteristics and of the MGMT methylation status of the lines with the tissues of origin shows that the cells in culture maintain the same characteristics.

Conclusions

Human cancer cell lines represent a support in the knowledge of tumour biology and in drug discovery through its facile experimental manipulation.

Trial registration

NCT 04180046.

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Cohesive cancer invasion of the biophysical barrier of smooth muscle

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Abstract

Smooth muscle is found around organs in the digestive, respiratory, and reproductive tracts. Cancers arising in the bladder, prostate, stomach, colon, and other sites progress from low-risk disease to high-risk, lethal metastatic disease characterized by tumor invasion into, within, and through the biophysical barrier of smooth muscle. We consider here the unique biophysical properties of smooth muscle and how cohesive clusters of tumor use mechanosensing cell–cell and cell–ECM (extracellular matrix) adhesion receptors to move through a structured muscle and withstand the biophysical forces to reach distant sites. Understanding integrated mechanosensing features within tumor cluster and smooth muscle and potential triggers within adjacent adipose tissue, such as the unique damage-associated molecular pattern protein (DAMP), eNAMPT (extracellular nicotinamide phosphoribosyltransferase), or visfatin, offers an opportunity to prevent the first steps of invasion and metastasis through the structured muscle.

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Dose adjustment of venetoclax when co-administered with posaconazole: clinical drug–drug interaction predictions using a PBPK approach

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Abstract

Purpose

Venetoclax, a targeted anticancer agent approved for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia, is a substrate of cytochrome P450 (CYP) 3A enzyme (CYP3A4). Posaconazole, commonly used to prevent invasive fungal infections in neutropenic patients with hematological malignancies, potently inhibits CYP3A4. The purpose of this evaluation was to predict venetoclax exposures following co-administration of posaconazole at doses not previously studied clinically.

Methods

Two physiologically based pharmacokinetic (PBPK) models were developed for posaconazole based on published parameters, one for an oral suspension and another for delayed released tablets. Parameter optimization, guided by sensitivity analyses, was conducted such that the models could replicate clinical exposures of posaconazole and drug–drug interactions with sensitive CYP3A substrates including venetoclax. The clinically verified posaconazole PBPK models were then utilized to predict DDI with a previously published venetoclax PBPK model at clinically relevant dosing scenarios.

Results

The posaconazole PBPK models predicted posaconazole exposure and DDI related fold changes with acceptable prediction errors for both posaconazole formulations. The model predicted exposures of venetoclax, when co-administered with a 300 mg QD dose of delayed release tablets of posaconazole, were in concordance with observed data. Increasing the posaconazole dose to 500 mg QD increased venetoclax exposures by about 12% relative to 300 mg QD, which were still within the venetoclax safe exposure range.

Conclusions

The posaconazole PBPK models were developed and clinically verified. Predictions using the robust PBPK model confirmed the venetoclax label recommendation of 70 mg in the presence of posaconazole at doses up to 500 mg QD.

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PDLIM2 prevents the malignant phenotype of hepatocellular carcinoma cells by negatively regulating β-catenin

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Implantation of rectosigmoid cancer in a preexisting anal fissure

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Abstract

Colorectal cancer (CRC) rarely spreads by implantation. We report a case of implantation of rectosigmoid cancer in an anal fissure. A 70-year-old woman with a 15-year medical history of anal fissure was referred to our hospital with anal pain of 3-month duration. Colonoscopy revealed a rectosigmoid tumor and a 10-mm submucosal tumor at the anal verge. Biopsy of the rectosigmoid and anal tumors revealed that both were moderately differentiated adenocarcinomas, and abdominoperineal resection (APR) was performed. The anal adenocarcinoma was surrounded by squamous cell epithelium and mainly proliferated in the submucosal and muscular layers. The patient was diagnosed as having rectosigmoid cancer with implantation of cancer in a preexisting anal fissure. The patient remains well 43 months post-surgery with no sign of recurrence. Implantation of CRC in anal fissure is a rare occurrence. Nevertheless, performing adequate anal examination of patients with CRC befor e surgery and during follow-up is necessary. Further, it is important to perform preoperative large bowel examination of patients with benign anal diseases to prevent implantation of CRC.

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Κυριακή 3 Ιανουαρίου 2021

Nursing Science

Secondary Traumatic Stress in Nursing: A Walker and Avant Concept Analysis
Nurses on the front lines of health care are impacted psychologically by their work and may experience secondary traumatic stress. The literature contains several different terms to explore concepts that describe the impact of traumatic patient experiences on the nurse, making it difficult to differentiate the concepts. Using the Walker and Avant method of analysis, the author reviewed nursing-specific publications within the last 10 years and seminal works to develop a purer meaning of secondary traumatic stress and distinguish it from other related terms. A more precise definition of secondary traumatic stress will allow for the advancement of research related to awareness and prevention in nursing. Correspondence: Marni B. Kellogg, PhD, RN, CPN, CNE, University of Massachusetts Dartmouth, 285 Old Westport Rd, Dartmouth, MA, 02747 (mkellogg@umassd.edu). The author has no acknowledgments or disclosures. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Symptom Management Theory: Analysis, Evaluation, and Implications for Caring for Adults With Cancer
A detailed analysis of Symptom Management Theory (SMT) along with its extent of use and implications for adults with cancer as demonstrated in 20 oncology research studies is reported. SMT provides useful guidance for adult oncology research and nursing practice. Theory dimension most researched in cancer was symptom experience. Although theory assertions were demonstrated in 80% of the studies, it was used to an adequate extent only in 35% of them. Comparisons between cancer-related clinical outcomes with and without use of SMT, certain theory modifications, and future SMT-based studies involving longitudinal designs in this population are warranted. Correspondence: Asha Mathew, MBA, MSN, RN, RM, Department of Biobehavioral Nursing Science, College of Nursing, University of Illinois at Chicago, 845 S. Damen Ave, Room 1024, Chicago, IL 60612 (asolom8@uic.edu). This article was supported by the National Institute of Nursing Research of the National Institutes of Health under award no. K24NR015340. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare that they have no conflicts of interest. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Exploring Nurses' Perceptions of Safety: A Phenomenological Study
The purpose of the study is to explore the lived experiences of nurses with regard to their personal safety and to identify the fundamental structures underlying nurse safety. A qualitative descriptive phenomenological design, using the data analysis method proposed by Colaizzi, was used. Eleven nurses participated in the study between March and July 2019. The research findings indicated the fundamental structure of nurse safety encompasses 3 categories: "nurses' personal protection systems," "safety support systems," and "risk factors." The fundamental structure identified in this study can contribute to better understanding and insight regarding the safety of nurses. Correspondence: Seung Wan Kang, PhD, MD, Associate Professor, College of Nursing, Research Institute of Nursing Science, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, South Korea (drdemian@snu.ac.kr). Immeasurable appreciation for their support is extended to the nurses who participated and shared their stories and Dr Hack Sun Kim, who reviewed the results of the study. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.advancesinnursingscience.com). Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

A Critical Analysis of the American Nurses Association Position Statement on Workplace Violence: Ethical Implications
In 2015, the American Nurses Association issued a position statement on workplace violence. An authoritative, disciplinary position is critically important to inform policies and recommendations addressing this significant issue in nursing. Position statements and policies should reflect disciplinary values. A discourse analysis of this position statement was performed through the lens of nursing ethics. The position statement endorses a zero-tolerance response, which is moralist, punitive, and questionably effective. It problematically presents patient and coworker violence as equivalent. Promotion of this position has the potential to erode public trust and lead us down a path of criminalizing illness behaviors. Correspondence: Darcy Copeland, PhD, RN, University of Northern Colorado, Campus Box 125, Gunter Hall, Greeley, CO 80639 (Darcy.copeland@unco.edu). The author would like to thank Dr Lorna Hutchison for reviewing this article. The author has disclosed that she has no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Integrity of Databases for Literature Searches in Nursing: Avoiding Predatory Journals
The quality of literature used as the foundation to any research or scholarly project is critical. The purpose of this study was to analyze the extent to which predatory nursing journals were included in credible databases, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus, commonly used by nurse scholars when searching for information. Findings indicated that no predatory nursing journals were currently indexed in MEDLINE or CINAHL, and only one journal was in Scopus. Citations to articles published in predatory nursing journals are not likely found in a search using these curated databases but rather through Google or Google Scholar search engines. Correspondence: Marilyn H. Oermann, PhD, RN, ANEF, FAAN, Duke University School of Nursing, DUMC 3322, 307 Trent Dr, Durham, NC 27710 (marilyn.oermann@duke.edu). Peggy L. Chinn, PhD, RN, FAAN, Editor, Advances in Nursing Science, is a member of our research team and contributed to the study and preparation of the manuscript. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

End-of-Life Care Terminology: A Scoping Review
The purpose of this scoping review is to present an overview of terms found in publications associated with end-of-life care management that can impact decision making by patients, health care providers, and researchers. Connotative terminology and syntax can influence the decision-making approach and process. We examined 49 publications for positive, negative, and neutral connotations. We consistently found negative terminology in the publications. To advance the development of nursing knowledge regarding end-of-life care, researchers should be aware of their biases of terminology and syntax use. We propose modifications to language used in end-of-life care planning models and literature can improve care congruency. Correspondence: Zahra Rahemi, PhD, RN, College of Behavioral, Social and Health Sciences, School of Nursing, Clemson University, 116 Edwards Hall, Clemson, SC 29634 (zrahemi@clemson.edu). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Black Female Sexuality: Intersectional Identities and Historical Contexts
Black females experience significant sexual health disparities. Intersectionality theory offers nurses a framework to address health disparities. Intersectionality theory examines how categorical identities of difference confer power or oppression, affect social interactions, and influence individuals' engagement with institutional structures. This secondary analysis of qualitative data details the damaging effects that power, oppression, and disadvantaged identities have on the sexual health of Black women. Twenty participants explained how the intersection of race, gender, age, education, and sexuality influences sexual health risk. Our expanded model of intersectionality theory emphasizes historical context with implications for research, practice, and education to promote health equity. Correspondence: Natasha Crooks, PhD, RN, Department of Human Development Nursing Science, University of Illinois Chicago College of Nursing, 845 S. Damen Ave, Room 816, Chicago, IL 60612 (ncrooks@uic.edu). This study was funded by the National Institute of Nursing Research, Pre-doctoral Fellowship Ruth L. Kirschstein National Research Service Award (F31NR016624), principal investigator Natasha Crooks. We would like to acknowledge and thank the participants who shared their personal stories. We would also like to acknowledge the support from the University of Wisconsin-Madison, Public Health and Dane County, and the Allied Wellness Center. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

A Conceptual Framework of Self-advocacy in Women With Cancer
Researchers define self-advocacy as the ability of an individual with cancer to overcome challenges in getting their preferences, needs, and values met. While imperative in all health care settings, self-advocacy is especially important in cancer care. The goal of this article is to present a conceptual framework for self-advocacy in cancer. We review foundational studies in self-advocacy, define the elements of the conceptual framework, discuss underlying assumptions of the framework, and suggest future directions in this research area. This framework provides an empirical and conceptual basis for studies designed to understand and improve self-advocacy among women with cancer. Correspondence: Teresa H. Thomas, PhD, RN, University of Pittsburgh School of Nursing, 3500 Victoria St, Ste 440, Pittsburgh, PA 15261 (t.thomas@pitt.edu). The authors want to dedicate this article to the late Susan M. Cohen, PhD, APRN, FAAN. She was a dedicated member of our research team and brought clarity of thought, enthusiasm, and reassurance to each of our studies described in this article. As a mentor, she endlessly supported this work and the development of all of her mentees. Without her guidance, along with that of our entire team of mentors and collaborators, this work would never have reached fruition. The following funding supported this article: American Cancer Society Mentored Research Scholar Grant MSRG-18-051-51 (Thomas), National Palliative Care Research Center Career Development Award (Thomas), American Cancer Society, Doctoral Degree Scholarship in Cancer Nursing DSCN-14-077-01-SCN (Thomas), National Institute of Nursing Research/National Institute of Health F31NR014066 (Thomas), National Institute of Nursing Research/National Institute of Health T32NR0111972 (Bender), National Institute of Nursing Research/National Institute of Health R01NR010735 (Donovan), Judith A. Erlen Nursing PhD Student Research Award (Thomas), Nightingale Awards of Pennsylvania, Doctoral Student Research Award (Thomas), Oncology Nursing Foundation, Doctoral Student Award (Thomas), Sigma Theta Tau International, Rosemary Berkel Crisp Research Award (Thomas), The Rockefeller University's Heilbrunn Family Center for Research Nursing, Heilbrunn Nurse Scholar (Thomas) Award, and Palliative Research Center (PaRC) at the University of Pittsburgh (Schenker). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Advancing Nursing Policy Advocacy Knowledge: A Theoretical Exploration
Nursing policy advocacy continues to be recognized as a key part of a nurse's role by educators, professional associations, and regulators. Despite normative calls on nurses to engage in political action and advocacy, limited theories, models, and frameworks exist to support this practice within nursing. Using Walt and Gilson's Health Policy Triangle Framework, this article explores the theoretical underpinnings of policy advocacy to enhance nursing's contemporary role in advancing social justice. Specific consideration is placed on the type of nursing and policy knowledge and perspectives required to understand policy content, contexts, processes, and actors. Correspondence: Patrick Chiu, RN, MPH, Faculty of Nursing, 4-171 Edmonton Clinic Health Academy, University of Alberta, Edmonton, AB T6G 1C9, Canada (pakcheon@ualberta.ca). The author acknowledges the valuable feedback provided by Professor Jill White, PhD, MEd, MHPol, RN, RM, FAAN, Professor Emerita, University of Sydney, Australia, and the University of Technology Sydney; and Joanne Olson, PhD, RN, FAAN, Professor, Faculty of Nursing, University of Alberta. The author has disclosed that he has no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Properties of Situation-Specific Theories and Neo-pragmatism
The purpose of this article is to discuss whether the properties of existing situation-specific theories are congruent with the philosophical stance of neo-pragmatism. A literature review was conducted using PubMed, CINAHL, and PsycInfo with keywords of "situation-specific theory" and "nursing." Fifteen situation-specific theories were included in the analysis. The properties of existing situation-specific theories included "high specificity and low level of abstraction," "context understanding," "direct linkages to research and practice," and "reflecting diversities and complexities with limited generalizability." Finally, the findings are discussed in terms of their linkages to the major tenets of neo-pragmatism. Correspondence: Eun-Ok Im, PhD, MPH, RN, CNS, FAAN, Nell Hodgson Woodruff School of Nursing, Emory University, 1520 Clifton Rd, Atlanta GA 30322 (eun.ok.im@emory.edu). The author has disclosed that she has no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.


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