RESUMO
BACKGROUND: The COVID-19 pandemic has required healthcare systems to transform the delivery of care. Although the core principles of care for patients with cancer have not changed, this pandemic has led to heightened awareness concerning the fragility of patients with cancer and how healthcare systems can protect them. OBJECTIVES: The aims were to identify and implement inpatient and ambulatory care clinical practice changes during the COVID-19 pandemic, based on defining moments and coping strategies from clinical oncology nurses, advanced practice RNs, nurse leaders, and researchers. METHODS: This article presents a Lean Six Sigma framework, accompanied by numerous rapid cycle tests of change. FINDINGS: The COVID-19 pandemic required clinical healthcare providers at the authors' institution to focus on seven priority areas. Nurses tested and implemented practice changes.
Assuntos
Adaptação Psicológica , Assistência Ambulatorial/normas , COVID-19/enfermagem , Pessoal de Saúde/psicologia , Neoplasias/enfermagem , Enfermagem Oncológica/normas , Medicina Preventiva/normas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Guias de Prática Clínica como Assunto , SARS-CoV-2 , Estresse PsicológicoRESUMO
Black raspberries (BRB) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce proinflammatory and antiapoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCC) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and noninvolved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of prosurvival genes (AURKA, BIRC5, EGFR) and proinflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated grade 3-4 toxicities or adverse events, and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark antiapoptotic and proinflammatory molecular biomarkers were overexpressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. As these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Neoplasias Bucais/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Fitoterapia , Extratos Vegetais/farmacologia , Rubus/química , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Frutas/química , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/efeitos dos fármacos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Compostos Fitoquímicos/farmacologia , PrognósticoRESUMO
The presence of RD(INK4/ARF) (RD) enhancer in the INK4-ARF locus provides a novel mechanism to simultaneously increase the transcription of p15(INK4b) (p15), p14ARF (p14), and p16(INK4a) (p16). While such upregulation can be repressed through interactions between RD and oncoproteins CDC6 and BMI1, little is known about the involvement of RD in cancer. In this study we investigated RD deletions in 30 squamous cell carcinoma of the head and neck (SCCHN) and the patient-matched High At-Risk Mucosa specimens (HARM, "phenotypically normal" tissues neighboring SCCHN foci but beyond the surgical resection margin). RD was deleted (homozygously/heterozygously) in SCCHN and HARM at the incidence of 36.7% (11/30) and 13.3% (4/30), respectively. In comparison, no RD deletion was detected in 26 oral buccal brush biopsy specimens from healthy donors. Both p16 and p14 were lowly expressed in SCCHN and HARM, and their mRNA expression levels were positively associated with each other (P < 0.01). Moreover, BMI1 was highly expressed in both SCCHN and HARM, and BMI1 overexpression was associated with p16 downregulation in SCCHN (P < 0.05). These results indicate that RD deletion and BMI1 overexpression frequently occur in the early stage of oral carcinogenesis and BMI1 overexpression may downregulate the transcription of p16 and p14 through interfering with RD.
Assuntos
Carcinoma de Células Escamosas/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Regulação Neoplásica da Expressão Gênica , Loci Gênicos , Neoplasias de Cabeça e Pescoço/genética , Proteína Supressora de Tumor p14ARF/genética , Feminino , Deleção de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Repressor Polycomb 1/genética , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND/AIM: While aberrant expression of cyclin-dependent kinase-4 (CDK4) has been found in squamous cell carcinoma of the head and neck (SCCHN), the associations between CDK4 and its regulators, namely, cyclin D1, cyclin E, gankyrin, SEI1, and BMI1 in gene expression remain to be explored. Herein we investigated the mRNA profiles of these oncogenes and their interrelations in different oral lesion tissues. MATERIALS AND METHODS: Thirty SCCHN specimens and patient-matched high at-risk mucosa (HARM) and 16 healthy control specimens were subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. RESULTS: The mRNA levels of CDK4, cyclin D1, gankyrin, SEI1, BMI1 were significantly elevated in both HARM and SCCHN (in comparison with control specimens), and statistically significant correlations were found among these markers in gene expression. CONCLUSION: Up-regulation of CDK4 and its regulators takes place in oral cancer progression in a coordinate manner, and HARM and SCCHN share a similar molecular signature within the CDK4-pRB pathway.