scholarly journals Distinct Binding Preferences between Ras and Raf Family Members and the Impact on Oncogenic Ras Signaling

2019 ◽  
Vol 76 (6) ◽  
pp. 872-884.e5 ◽  
Author(s):  
Elizabeth M. Terrell ◽  
David E. Durrant ◽  
Daniel A. Ritt ◽  
Nancy E. Sealover ◽  
Erin Sheffels ◽  
...  
Keyword(s):  
Family Members ◽  
Ras Signaling ◽  
Oncogenic Ras ◽  
The Impact

scholarly journals The Role of Wild-Type RAS in Oncogenic RAS Transformation

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 662
Author(s):  
Erin Sheffels ◽  
Robert L. Kortum
Keyword(s):  
Family Members ◽  
Protein Product ◽  
Therapeutic Resistance ◽  
Ras Signaling ◽  
Ras Proteins ◽  
Wild Type ◽  
Oncogenic Ras ◽  
Downstream Effector ◽  
Ras Family

The RAS family of oncogenes (HRAS, NRAS, and KRAS) are among the most frequently mutated protein families in cancers. RAS-mutated tumors were originally thought to proliferate independently of upstream signaling inputs, but we now know that non-mutated wild-type (WT) RAS proteins play an important role in modulating downstream effector signaling and driving therapeutic resistance in RAS-mutated cancers. This modulation is complex as different WT RAS family members have opposing functions. The protein product of the WT RAS allele of the same isoform as mutated RAS is often tumor-suppressive and lost during tumor progression. In contrast, RTK-dependent activation of the WT RAS proteins from the two non-mutated WT RAS family members is tumor-promoting. Further, rebound activation of RTK–WT RAS signaling underlies therapeutic resistance to targeted therapeutics in RAS-mutated cancers. The contributions of WT RAS to proliferation and transformation in RAS-mutated cancer cells places renewed interest in upstream signaling molecules, including the phosphatase/adaptor SHP2 and the RasGEFs SOS1 and SOS2, as potential therapeutic targets in RAS-mutated cancers.

Qualitative Examination of the Impact of Rural Veterans' Functioning on Their Family Members

2013 ◽  
Author(s):  
Michelle M. Kawasaki ◽  
Julia Whealin ◽  
Dawna Nelson ◽  
Jui-Feng Tatekawa-Chen
Keyword(s):  
Family Members ◽  
The Impact

scholarly journals EFFECT OF ADVERSE CHILDHOOD EXPERIENCES ON DAILY SUPPORT TO FAMILY AND EMOTIONAL WELL-BEING IN ADULTHOOD

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S235-S235
Author(s):  
Jooyoung Kong ◽  
Yin Liu ◽  
David Almeida
Keyword(s):  
Negative Affect ◽  
Family Relationships ◽  
Emotional Support ◽  
Adverse Childhood Experiences ◽  
Family Members ◽  
Well Being ◽  
National Study ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
The Impact

Abstract Extensive evidence suggests that adverse childhood experiences (ACEs) can lead to negative health effects across a lifetime. This study examines the impact of ACEs on the frequency of providing daily support (i.e., unpaid assistance, emotional support, and disability-related assistance) to family members and the moderating effects of ACEs in the association between providing daily support to family and daily negative affect. Using the National Study of Daily Experiences II, we analyzed a total of 14,912 daily interviews from 2,022 respondents aged 56 on average. Key results showed that a greater number of ACEs were associated with providing more frequent emotional support to family. We also found the significant interaction effect that adults with more ACEs showed greater negative affect on the days when they provided assistance to family members with disabilities. The findings underscore the long-term negative impact of ACEs on daily well-being in the context of family relationships.

scholarly journals Family reported outcomes, an unmet need in the management of a patient's disease: appraisal of the literature

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
R. Shah ◽  
F. M. Ali ◽  
A. Y. Finlay ◽  
M. S. Salek
Keyword(s):  
Quality Of Life ◽  
Family Members ◽  
Unmet Need ◽  
Reliability And Validity ◽  
Chronic Health Condition ◽  
Family Quality Of Life ◽  
Good Reliability ◽  
Huge Impact ◽  
The Impact

Abstract Background A person’s chronic health condition or disability can have a huge impact on the quality of life (QoL) of the whole family, but this important impact is often ignored. This literature review aims to understand the impact of patients' disease on family members across all medical specialities, and appraise existing generic and disease-specific family quality of life (QoL) measures. Methods The databases Medline, EMBASE, CINHAL, ASSIA, PsycINFO and Scopus were searched for original articles in English measuring the impact of health conditions on patients' family members/partner using a valid instrument. Results Of 114 articles screened, 86 met the inclusion criteria. They explored the impact of a relative's disease on 14,661 family members, mostly 'parents' or 'mothers', using 50 different instruments across 18 specialities including neurology, oncology and dermatology, in 33 countries including the USA, China and Australia. These studies revealed a huge impact of patients' illness on family members. An appraisal of family QoL instruments identified 48 instruments, 42 disease/speciality specific and six generic measures. Five of the six generics are aimed at carers of children, people with disability or restricted to chronic disease. The only generic instrument that measures the impact of any condition on family members across all specialities is the Family Reported Outcome Measure (FROM-16). Although most instruments demonstrated good reliability and validity, only 11 reported responsiveness and only one reported the minimal clinically important difference. Conclusions Family members' QoL is greatly impacted by a relative's condition. To support family members, there is a need for a generic tool that offers flexibility and brevity for use in clinical settings across all areas of medicine. FROM-16 could be the tool of choice, provided its robustness is demonstrated with further validation of its psychometric properties.

scholarly journals Highly metastatic claudin-low mammary cancers can originate from luminal epithelial cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Patrick D. Rädler ◽  
Barbara L. Wehde ◽  
Aleata A. Triplett ◽  
Hridaya Shrestha ◽  
Jonathan H. Shepherd ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Epithelial Cells ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Ras Signaling ◽  
Preneoplastic Lesions ◽  
Independent Manner ◽  
Oncogenic Ras ◽  
Luminal Epithelial Cells

AbstractClaudin-low breast cancer represents an aggressive molecular subtype that is comprised of mostly triple-negative mammary tumor cells that possess stem cell-like and mesenchymal features. Little is known about the cellular origin and oncogenic drivers that promote claudin-low breast cancer. In this study, we show that persistent oncogenic RAS signaling causes highly metastatic triple-negative mammary tumors in mice. More importantly, the activation of endogenous mutant KRAS and expression of exogenous KRAS specifically in luminal epithelial cells in a continuous and differentiation stage-independent manner induces preneoplastic lesions that evolve into basal-like and claudin-low mammary cancers. Further investigations demonstrate that the continuous signaling of oncogenic RAS, as well as regulators of EMT, play a crucial role in the cellular plasticity and maintenance of the mesenchymal and stem cell characteristics of claudin-low mammary cancer cells.

scholarly journals 545. The Impact of COVID-19 on African Americans’ Health Attitudes and Information Seeking Behavior

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S338-S339
Author(s):  
Katherine Kricorian ◽  
Ozlem Equils ◽  
Karin Kricorian ◽  
Brianna Rochebrun
Keyword(s):  
African Americans ◽  
Information Seeking ◽  
Disease Incidence ◽  
Family Members ◽  
National Sample ◽  
Health Attitudes ◽  
Health News ◽  
Before And After ◽  
Science And Government ◽  
The Impact

Abstract Background African-Americans suffer a disproportionate impact from COVID-19, comprising about 24% of deaths while representing 13% of the US population. We conducted a study to understand COVID-19’s impact on African-Americans’ health attitudes. Methods In April 2020, we surveyed online a national sample of US adults on their health attitudes and behaviors before and after the COVID-19 outbreak. Comparisons were analyzed using chi-squared tests. Results A total of 2,544 individuals completed the survey: 473 African-Americans, 282 Hispanics and 1,799 Caucasians responded. The mean ages of each group were 41.4 ± 11 years, 38.0 ± 11 years and 45.7 ± 13 years, respectively. Before COVID-19, African-Americans were least likely to report they had trust in science (53% vs. 68% for Hispanics and 77% for Caucasians; p< .01) and government (16% vs. 27% and 28%; p< .01). After COVID-19, the percentage of African-Americans who had trust in science and government fell further to 44% (p< .01) and 9% (p< .01), respectively, and remained significantly lower than the other two groups. Twice as many African-Americans vs. Caucasians stopped following science and health news after COVID-19 (9% vs. 4%, p< .01). The percentage of African-Americans who reported anxiety about their health rose from 30% pre-COVID to 53% after the outbreak (p< .01), and the percentage who reported anxiety about their family members’ health rose from 35% to 61% (p< .01). Only 25% of African-Americans surveyed agreed that if they contracted COVID-19, they were confident they would get the healthcare needed. Conclusion After COVID-19, African-Americans’ trust in science and government fell and a meaningful percentage stopped following science and health news, possibly reducing access to important health information. The percentage of African-Americans reporting anxiety about the future, about their health and about their family members’ health all increased significantly after COVID-19. Only a minority of African-Americans agreed they would get the needed healthcare if they contracted COVID-19. These findings have implications for the mental health and behavioral impacts of COVID-19 on African-Americans and for the development of health communications to high-disease-incidence populations. Disclosures All Authors: No reported disclosures

scholarly journals Parental perspective: The role of prostheses and prosthetics services in adjusting to a child’s upper limb difference

2020 ◽  
pp. 1-7
Author(s):  
Tara Sims
Keyword(s):  
Coping Strategies ◽  
Peer Support ◽  
Upper Limb ◽  
Family Members ◽  
Parental Adjustment ◽  
Prosthetic Devices ◽  
The Family ◽  
The Impact

BACKGROUND: The impact of paediatric upper limb difference may extend beyond the child themselves to their parents and other family members. Previous research has found that feelings of shock, numbness and loss are common amongst parents and that peer support can be a buffer against stress. OBJECTIVE: The current study aimed to explore the experiences of parents of children with limb difference, and the role of services and prosthetic devices in these experiences. METHODS: Nine parents of children with limb difference participated in either a group (n= 2) or individual (n= 7) interview. RESULTS: Analysis of the interview transcripts revealed four themes – ‘grief and guilt’, ‘prosthesis as a tool for parental adjustment’, ‘support’ and ‘fun and humour’. CONCLUSIONS: Parents may employ coping strategies to help them adjust to their child’s limb difference, including use of a prosthesis, accessing support from statutory services and peers, and use of fun and humour within the family.

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