Stress as a predictor of tumor growth and development of metastases.

e24124 Background: The aims of this study were to examine; the predictors of perceived stress; and the associations between perceived stress and tumor growth and development of metastases as well as the mediational role of inflammatory biomarkers. Methods: This study is prospective in design. A battery of questionnaires, including a sociodemographic characteristic and the Perceived Stress Scale, was collected at baseline from patients diagnosed with solid tumors at various stages of treatment. Disease progression was measured over a 12-month period. Poverty threshold was determined using the U.S. Department of Health & Human Services 2020 poverty guidelines. Computerized tomography and Magnetic Resonance Imaging scans were assessed for disease progression between baseline and 12 months using Response Evaluation Criteria in Solid Tumors. Blood was collected and serum levels of IL-2, IL-1a, IL-1b, TNF-a, IL-6, and IL-8 were assessed. The predictors of stress include sociodemographic and disease specific characteristics. Primary outcomes were tumor growth and development of metastases. Descriptive statistics, correlations, and ordinal and linear regression were performed to assess the aims. Results: Of 159 patients diagnosed with cancer, 47.8% were male, mean age was 62.97 (SD = 10.35), 89.3% were Caucasian, and 13.8% met poverty guidelines. Significant predictors of stress were age (b=-.151, p=0.029, 95% C.I.=-2.86-.016) and income below the poverty threshold (b= 5.615, p=0.007, 95% C.I.=1.596-9.635). Gender was the only sociodemographic and disease specific factor significantly associated with disease progression. After adjusting for gender, greater perceived stress was associated with tumor growth and development of metastases (p =0.029), accounting for 33.3% of the variance. Circulating cytokines were significantly related to disease progression [IL-1a, p=0.020; IL-1b, p=0.011; IL-6, p<0.001; and IL-8, p<0.001] but not stress [IL-1a, p=0.369; IL-1b p=0.292; IL-2, p=0.470; IL6 p=0.406; and IL8, p=0.401]. Conclusions: Future research should evaluate inflammation in the tumor microenvironment as well as neutrophils and tumor suppressor genes as potential mediators between stress and disease progression.

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Physiology of Larval Feeding

10.1093/oso/9780198786962.003.0009 ◽

2018 ◽

Keyword(s):

Growth And Development ◽

Marine Invertebrate ◽

Larval Growth ◽

Circulatory System ◽

Future Research ◽

Larval Feeding ◽

Digestive Physiology ◽

Larval Body ◽

The Individual ◽

Invertebrate Larvae

The functional properties of marine invertebrate larvae represent the sum of the physiological activities of the individual, the interdependence among cells making up the whole, and the correct positioning of cells within the larval body. This chapter examines physiological aspects of nutrient acquisition, digestion, assimilation, and distribution within invertebrate larvae from an organismic and comparative perspective. Growth and development of larvae obviously require the acquisition of “food.” Yet the mechanisms where particulate or dissolved organic materials are converted into biomass and promote development of larvae differ and are variably known among groups. Differences in the physiology of the digestive system (secreted enzymes, gut transit time, and assimilation) within and among feeding larvae suggest the possibility of an underappreciated plasticity of digestive physiology. How the ingestion of seawater by and the existence of a circulatory system within larvae contribute to larval growth and development represent important topics for future research.

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Accuracy of State-Level Surveillance during Emerging Outbreaks of Respiratory Viruses: A Model-Based Assessment

Medical Decision Making ◽

10.1177/0272989x211022276 ◽

2021 ◽

pp. 0272989X2110222

Author(s):

Yuwen Gu ◽

Elise DeDoncker ◽

Richard VanEnk ◽

Rajib Paul ◽

Susan Peters ◽

...

Keyword(s):

Growth Rate ◽

Data Collection ◽

Disease Progression ◽

Health Care Providers ◽

Growth Rates ◽

State Level ◽

Future Research ◽

Care Providers ◽

State Surveillance ◽

First Come First Serve

It is long perceived that the more data collection, the more knowledge emerges about the real disease progression. During emergencies like the H1N1 and the severe acute respiratory syndrome coronavirus 2 pandemics, public health surveillance requested increased testing to address the exacerbated demand. However, it is currently unknown how accurately surveillance portrays disease progression through incidence and confirmed case trends. State surveillance, unlike commercial testing, can process specimens based on the upcoming demand (e.g., with testing restrictions). Hence, proper assessment of accuracy may lead to improvements for a robust infrastructure. Using the H1N1 pandemic experience, we developed a simulation that models the true unobserved influenza incidence trend in the State of Michigan, as well as trends observed at different data collection points of the surveillance system. We calculated the growth rate, or speed at which each trend increases during the pandemic growth phase, and we performed statistical experiments to assess the biases (or differences) between growth rates of unobserved and observed trends. We highlight the following results: 1) emergency-driven high-risk perception increases reporting, which leads to reduction of biases in the growth rates; 2) the best predicted growth rates are those estimated from the trend of specimens submitted to the surveillance point that receives reports from a variety of health care providers; and 3) under several criteria to queue specimens for viral subtyping with limited capacity, the best-performing criterion was to queue first-come, first-serve restricted to specimens with higher hospitalization risk. Under this criterion, the lab released capacity to subtype specimens for each day in the trend, which reduced the growth rate bias the most compared to other queuing criteria. Future research should investigate additional restrictions to the queue.

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810 Preliminary safety, tolerability and efficacy results of KN026 in combination with KN046 in patients with HER2 aberrated solid tumors

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0810 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A861-A861

Author(s):

Jifang Gong ◽

Lin Shen ◽

Zhi Dong ◽

Dan Liu ◽

June Xu ◽

...

Keyword(s):

Disease Progression ◽

Solid Tumors ◽

Dose Escalation ◽

Bispecific Antibody ◽

Her2 Overexpression ◽

Her2 Positive ◽

Her2 Mutation ◽

Grade 3 ◽

Experienced Grade ◽

Low Expression

BackgroundHER2 potently inhibits innate immunity through cGAS–STING signaling [Ref],meanwhile HER2 antibody induced ADCP will also lead to macrophage mediated immune suppression. Both preclinical and clinical studies have suggested a coordination of engagement of innate and adaptive immunity with the combination of an anti-HER2 antibody and an immune checkpoint blockade. KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1/CD80 and CTLA-4 interaction with CD80/CD86. Here we reported the interim results from an ongoing phase Ib dose escalation and expansion study assessing the safety, tolerability and preliminary efficacy for KN026 in combination with KN046 in Patients with HER2 aberrated solid tumors.MethodsThis study enrolled pts with solid tumors who failed available standard of care, HER2 aberration status confirmed locally (HER2 mutation, HER2 amplification and/or HER2 overexpression). Eligible pts received combination of KN026 and KN046 at three dose levels until disease progression, unacceptable toxicity or withdrawal of informed consent (DL1: KN026 20 mg/kg Q2W + KN046 3 mg/kg Q2W; DL2: KN026 20 mg/kg Q2W with loading on Days 1, 8 of Cycle 1 + KN046 5 mg/kg Q3W; DL3: KN026 30 mg/kg Q3W with loading on Days 1, 8 of Cycle 1 + KN046 5 mg/kg Q3W). Tumor response was evaluated Q8W per RECIST 1.1. Primary endpoint was DLT and key secondary endpoints were efficacy parameters (ORR, DOR, PFS).ResultsAs of the Sep. 08, 2020, 25 pts were enrolled into DL1 (n = 20, 3 for dose escalation), DL2 (n = 3) and DL3 (n = 2) (mGC/GEJ 15 pts; mCRC 8 pts; other solid tumors 2 pts). 15 pts remained on the study treatment and 10 pts discontinued treatment due to disease progression (n=5), death (n=2) and other reasons (n=3). 18 pts had HER2-positive status (12 of 18 failed previous trastuzumab therapy), 2 pts had HER2 mutation and 5 pts had HER2 low expression (without FISH amplification). No DLTs were observed. No pts experienced LVEF decreased or other clinically meaningful cardiac AEs. Treatment-related TEAEs occurred in 23 (92%) pts, of which 6 (24%) pts experienced grade 3 or above treatment-related TEAEs. 11 (44%) pts experienced irAEs, majority were of grade 1 or 2 except that 1 patient experienced grade 3 immune-mediated endocrinopathy. The most common (frequency ≥ 15%) KN026 or KN046 related TEAEs were infusion related reaction (n=11, 44.0%), anaemia (n=9, 36.0%), white blood cell count decreased (n=6, 24.0%), diarrhea (n=5, 20.0%), AST increased (n=5, 20.0%), platelet count decreased (n=5, 20.0%), rash (n=5, 20.0%) and ALT increased (n=4, 16.0%). The objective response rate in pts with HER2-positive tumors (n = 14 efficacy evaluable pts) was 9/14 (64.3%, 95% CI 35.1~87.2%) and disease control rate 13/14 (92.9%, 95% CI 66.1~99.8%). 4 out of 5 pts with HER2 mutation or low expression achieved SD including one patient with SD for more than 24 weeks. 2 death cases due to disease progression were reported, both only received one cycle of KN026 plus KN046 due to COVID-19 restriction.ConclusionsKN026 combined with KN046 is well tolerated and has demonstrated preliminary albeit profound anti-tumor activity in HER2-positive solid tumors.Trial RegistrationClinical trial information: NCT04040699ReferenceShiying Wu, Qian Zhang, Fei Zhang, et al. HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity. Nature Cell Biology 2019;21:1027–1040.

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Self-Care for Nurse Leaders in Acute Care Environment Reduces Perceived Stress: A Mixed-Methods Pilot Study Merits Further Investigation

Journal of Holistic Nursing ◽

10.1177/0898010116685655 ◽

2017 ◽

Vol 36 (1) ◽

pp. 79-90 ◽

Cited By ~ 4

Author(s):

Susan Mac Leod Dyess ◽

Angela S. Prestia ◽

Doren-Elyse Marquit ◽

David Newman

Keyword(s):

Mixed Methods ◽

Acute Care ◽

Perceived Stress ◽

Repeated Measures ◽

Self Care ◽

Nurse Leaders ◽

Future Research ◽

Care Practice ◽

Meditation Practice ◽

Significant Drop

Acute care practice settings are stressful. Nurse leaders face stressful demands of numerous competing priorities. Some nurse leaders experience unmanageable stress, but success requires self-care. This article presents a repeated measures intervention design study using mixed methods to investigate a self-care simple meditation practice for nurse leaders. Themes and subthemes emerged in association with the three data collection points: at baseline (pretest), after 6 weeks, and after 12 weeks (posttest) from introduction of the self-care simple meditation practice. An analysis of variance yielded a statistically significant drop in perceived stress at 6 weeks and again at 12 weeks. Conducting future research is merited.

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Anti-Cancer Effects of Zotarolimus Combined with 5-Fluorouracil Treatment in HCT-116 Colorectal Cancer-Bearing BALB/c Nude Mice

Molecules ◽

10.3390/molecules26154683 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4683

Author(s):

Geng-Ruei Chang ◽

Chan-Yen Kuo ◽

Ming-Yang Tsai ◽

Wei-Li Lin ◽

Tzu-Chun Lin ◽

...

Keyword(s):

Growth Factor ◽

Tumor Growth ◽

Nude Mice ◽

Colorectal Adenocarcinoma ◽

Transforming Growth Factor ◽

Colon Adenocarcinoma ◽

Future Research ◽

Related Factors ◽

Hct 116

Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1β, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.

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Trial in progress: Phase 1a/b study of PF-07284890 (brain-penetrant BRAF inhibitor) with/without binimetinib in patients with BRAF V600-mutant solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps3152 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS3152-TPS3152

Author(s):

Vivek Subbiah ◽

Martin Gutierrez ◽

Carey K. Anders ◽

George Ansstas ◽

Taofeek K. Owonikoko ◽

...

Keyword(s):

Disease Progression ◽

Solid Tumors ◽

Dose Level ◽

Solid Tumor ◽

Human Study ◽

Tumor Type ◽

Overall Response ◽

Secondary Endpoints ◽

Phase 1B ◽

Brain Involvement

TPS3152 Background: BRAF inhibitors have transformed treatment (Tx) for patients (pts) with BRAF V600-mutant cancers, but long-term efficacy is limited by disease progression in the brain, due to poor brain penetration. PF-07284890 is a potent, selective, highly brain-penetrant, small-molecule inhibitor of BRAF V600 mutations. This first in human study will assess the PK, safety, and preliminary clinical activity of PF-07284890, as monotherapy and in combination with binimetinib (MEK inhibitor), in pts with BRAF V600-mutated advanced solid tumors with/without brain metastases. Methods: Phase 1a/1b open-label, multicenter, dose-finding study (NCT04543188). Pts will be ≥18 y with a histologically confirmed advanced/metastatic solid tumor including primary brain tumor (PBT), confirmed BRAF V600 mutation, and presence/absence of brain involvement. Pts will have disease progression despite prior Tx without alternative Tx options. Pts with brain metastasis/PBT > 4 cm and/or symptomatic brain disease will be excluded initially, but allowed based on emerging PK. Phase 1a is a dose escalation study of PF-07284890 (monotherapy and combination). ̃35 pts will be enrolled to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of PF-07284890 (monotherapy and combination). Cohorts of 2-4 pts will be treated at each dose level of PF-07284890 until MTD/RDE determination (PF-07284890 starting dose: 50 mg QD; binimetinib 45 mg BID). Bayesian Logistic Regression Model will be used to inform dose level decisions. At least 6 pts each for monotherapy and combination will be treated at MTD/RDE. Phase 1a primary endpoints: Cycle 1 dose-limiting toxicities; MTD/RDE; AEs; lab abnormalities; and dose interruptions, modifications and discontinuations due to AEs. Secondary endpoints include PK parameters and overall response (RECIST; overall and intracranial; RANO for PBT). Phase 1b is a dose expansion and drug-drug interaction study to further evaluate PF-07284890 + binimetinib. Cohorts 1-4 (̃40 pts each) will enroll pts based on tumor type, brain involvement (asymptomatic/symptomatic), and prior Tx. Cohort 5 (̃20 pts) will include pts with any solid tumor including leptomeningeal metastases. Cohort 6 (̃10 pts) will assess the effect of PF-07284890 + binimetinib on CYP3A activity using midazolam as a substrate. Phase 1b primary endpoint: overall response (RECIST; overall and intracranial; RANO for PBT). Secondary endpoints: duration of response; progression-free survival; disease control rate; time to response; overall survival; AEs; lab abnormalities; and dose interruptions, modifications and discontinuations due to AEs; and PK parameters. For both Phase 1a and 1b, Tx will continue until disease progression, unacceptable toxicity or patient refusal. Study began enrolling pts in January 2021 and is ongoing. Clinical trial information: NCT04543188.

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IL6 receptor358Ala variant and trans-signaling are disease modifiers in amyotrophic lateral sclerosis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000631 ◽

2019 ◽

Vol 6 (6) ◽

pp. e631 ◽

Cited By ~ 8

Author(s):

Marlena Wosiski-Kuhn ◽

Mac Robinson ◽

Jane Strupe ◽

Phonepasong Arounleut ◽

Matthew Martin ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Disease Progression ◽

Interleukin 6 ◽

Serum Levels ◽

Interleukin 6 Receptor ◽

The Common ◽

Paired Serum ◽

Control Study ◽

Lateral Sclerosis

ObjectiveTo test the hypothesis that patients with amyotrophic lateral sclerosis (ALS) inheriting the common interleukin 6 receptor (IL6R) coding variant (Asp358Ala, rs2228145, C allele) have associated increases in interleukin 6 (IL6) and IL6R levels in serum and CSF and faster disease progression than noncarriers.MethodsAn observational, case-control study of paired serum and CSF of 47 patients with ALS, 46 healthy, and 23 neurologic disease controls from the Northeastern ALS Consortium Biofluid Repository (cohort 1) was performed to determine serum levels of IL6, sIL6R, and soluble glycoprotein 130 and compared across groups and IL6R genotype. Clinical data regarding disease progression from a separate cohort of 35 patients with ALS from the Wake Forest ALS Center (cohort 2) were used to determine change in ALSFRS-R scores by genotype.ResultsPatients with ALS had increased CSF IL6 levels compared with healthy (p < 0.001) and neurologic (p = 0.021) controls. Patients with ALS also had increased serum IL6 compared with healthy (p = 0.040) but not neurologic controls. Additive allelic increases in serum IL6R were observed in all groups (average increase of 52% with the presence of the IL6R C allele; p < 0.001). However, only subjects with ALS had significantly increased CSF sIL6R levels compared with controls (p < 0.001). When compared across genotypes, only patients with ALS inheriting the IL6R C allele exhibit increased CSF IL6. ALSFRS-R scores decreased more in patients with ALS with the IL6R C allele than in those without (p = 0.019).ConclusionsTheses results suggest that for individuals inheriting the IL6R C allele, the cytokine exerts a disease- and location-specific role in ALS. Follow-up, prospective studies are necessary, as this subgroup of patients may be identified as ideally responsive to IL6 receptor–blocking therapies.

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Predeath Grief, Resourcefulness, and Perceived Stress Among Caregivers of Partners With Young-Onset Dementia

Western Journal of Nursing Research ◽

10.1177/0193945918806689 ◽

2018 ◽

Vol 41 (7) ◽

pp. 973-989 ◽

Cited By ~ 2

Author(s):

Karie Ruekert Kobiske ◽

Abir K. Bekhet ◽

Mauricio Garnier-Villarreal ◽

Marilyn Frenn

Keyword(s):

Perceived Stress ◽

Online Survey ◽

Theoretical Framework ◽

Future Research ◽

Resilience Theory ◽

Moderating Effects ◽

Cross Sectional ◽

Young Onset ◽

Young Onset Dementia ◽

The Relationship

More than 200,000 Americans are currently diagnosed with young-onset dementia (YOD). YOD is dementia diagnosed prior to the age of 65. Most persons of YOD are cared for by their partners. Using the theoretical framework of Resilience Theory, this cross-sectional, correlational study examined the moderating effects of personal and social resourcefulness on the relationship between predeath grief and perceived stress among 104 YOD caregiving partners (life partners/spouses) using an online survey platform. Results indicated a large positive correlation between predeath grief and caregiver perceived stress ( r = .65; p < .001). Together predeath grief, personal resourcefulness and social resourcefulness explained 51.5% of the variance in perceived stress. Personal resourcefulness did not moderate the relationship. Social resourcefulness did positively moderate this relationship between predeath grief and perceived stress. These findings allow for a better understanding of the caregiving experience for a partner with YOD and creates opportunities for future research studies.

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Psychological Factors Influencing Life Satisfaction of Undergraduates

10.31234/osf.io/xdpfz ◽

2017 ◽

Author(s):

Bukunmi O Adewumi ◽

Olubukola Ajayi

Keyword(s):

Life Satisfaction ◽

Emotional Intelligence ◽

Perceived Stress ◽

Significant Influence ◽

Psychological Factors ◽

Satisfaction With Life ◽

Self Esteem ◽

Satisfaction With Life Scale ◽

Future Research ◽

Factors Influencing

This study was designed to assess the psychological factors influencing life satisfaction of undergraduates. The instruments used were Perceived Stress Scale (PSS), Wong and Law Emotional Intelligence Scale (WLEIS), Rosenberge Self-esteem Scale (RSS), and Satisfaction with Life Scale (SWLS). A total number of 190 participants were purposively selected across various faculties in Ekiti State University. Four hypotheses were tested using Independent t-test to find the effects of perceived stress, emotional intelligence, and self-esteem on life satisfaction. Multiple regression was used to find the joint and individual influences of these variables. The results showed that there is no significant influence of perceived stress on life satisfaction (t (75) = 1.23, p = .22, 95% CI [-1.14, 4.83). There is no significant influence of self-esteem on life satisfaction (t (51) = -1.31, p = .20, 95% CI [-5.28, 1.11), and there is no significant joint influence of perceived stress, emotional intelligence and self-esteem on life satisfaction (F (3,187) = 1.79, p = .15, R2 =.03). Additionally, perceived stress (β = .07, p = .33), emotional intelligence (β = .14, p = 054) and self-esteem (β = .02, p = .83) did not have independent influences on life satisfaction. Implications of the present findings for future research are discussed, as well as potential interventions for improving life satisfaction.

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IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment

Frontiers in Immunology ◽

10.3389/fimmu.2021.683332 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kewei Liu ◽

Ai Huang ◽

Jun Nie ◽

Jun Tan ◽

Shijie Xing ◽

...

Keyword(s):

Tumor Microenvironment ◽

Tumor Growth ◽

Immune Cells ◽

Immune Checkpoint Blockade ◽

Future Research ◽

Barr Virus ◽

Promote Tumor Growth ◽

Epstein Barr ◽

Mechanistic Basis ◽

Tumor Growth And Metastasis

Interleukin-35 (IL-35) is a heterodimeric cytokine composed of Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35 that has recently been shown to play diverse and important roles in the tumor microenvironment (TME). Owing to its immunosuppressive activity and ability to promote tumor growth and progression, IL-35 is widely recognized as a key mediator of TME status. Immune cells are key mediators of diverse tumor-related phenotypes, and immunosuppressive cytokines such as IL-35 can promote tumor growth and metastasis in TME. These influences should be considered together. Since tumor immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance, a new target or efficacy enhancing factor is urgently needed. Suppressing IL-35 production and activity has been demonstrated as an effective factor that inhibits tumor cells viability, and further investigation of this cytokine is warranted. However, the mechanistic basis for IL-35-mediated regulation of immune cells in the TME remains to be fully clarified. In the present review, we explore the roles of IL-35 in regulating immune cells within the TME. In addition, we highlight IL-35 as a specific immunological target and discuss its possible relevance in the context of immunotherapy. Lastly, we sought to summarize potential future research directions that may guide the advancement of current understanding regarding the role of this important cytokine as a regulator of oncogenesis.

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