3 research outputs found
Multi-Domain Screening:Identification of Patientās Risk Profile Prior to Head-and-Neck Cancer Treatment
Background: Head-and-neck cancer (HNC) can give rise to oropharyngeal dysphagia (OD), malnutrition, sarcopenia, and frailty. Early identification of these phenomena in newly diagnosed HNC patients is important to reduce the risk of complications and to improve treatment outcomes. The aim of this study was (1) to determine the prevalence of the risk of OD, malnutrition, sarcopenia, and frailty; and (2) to investigate the relation between these phenomena and patientsā age, performance status, and cancer group staging. Methods: Patients (N = 128) underwent multi-domain screening consisting of the Eating Assessment Tool-10 for OD, Short Nutritional Assessment Questionnaire and BMI for malnutrition, Short Physical Performance Battery and Hand Grip Strength for sarcopenia, and Distress Thermometer and Maastricht Frailty Screening Tool for frailty. Results: 26.2%, 31.0%, 73.0%, and 46.4% of the patients were at risk for OD, malnutrition, sarcopenia, or frailty, respectively. Patients with an advanced cancer stage had a significantly higher risk of OD and high levels of distress prior to cancer treatment. Conclusions: This study identified the risk profile of newly diagnosed HNC patients using a standardized āquick and easyā multi-domain screening prior to cancer treatment.</p
Adenosine monophosphateāactivated protein kinase is elevated in human cachectic muscle and prevents cancerāinduced metabolic dysfunction in mice
Abstract Background Metabolic dysfunction and cachexia are associated with poor cancer prognosis. With no pharmacological treatments, it is crucial to define the molecular mechanisms causing cancerāinduced metabolic dysfunction and cachexia. Adenosine monophosphateāactivated protein kinase (AMPK) connects metabolic and muscle mass regulation. As AMPK could be a potential treatment target, it is important to determine the function for AMPK in cancerāassociated metabolic dysfunction and cachexia. We therefore established AMPK's roles in cancerāassociated metabolic dysfunction, insulin resistance and cachexia. Methods In vastus lateralis muscle biopsies from nĀ =Ā 26 patients with nonāsmall cell lung cancer (NSCLC), AMPK signalling and protein content were examined by immunoblotting. To determine the role of muscle AMPK, male mice overexpressing a dominantānegative AMPKĪ±2 (kinaseādead [KiDe]) specifically in striated muscle were inoculated with Lewis lung carcinoma (LLC) cells (wild type [WT]: nĀ =Ā 27, WTĀ +Ā LLC: nĀ =Ā 34, mAMPKāKiDe: nĀ =Ā 23, mAMPKāKiDeĀ +Ā LLC: nĀ =Ā 38). Moreover, male LLCātumourābearing mice were treated with (nĀ =Ā 10)/without (nĀ =Ā 9) 5āaminoimidazoleā4ācarboxamide ribonucleotide (AICAR) to activate AMPK for 13Ā days. Littermate mice were used as controls. Metabolic phenotyping of mice was performed via indirect calorimetry, body composition analyses, glucose and insulin tolerance tests, tissueāspecific 2ā[3H]deoxyādāglucose (2āDG) uptake and immunoblotting. Results Patients with NSCLC presented increased muscle protein content of AMPK subunits Ī±1, Ī±2, Ī²2, Ī³1 and Ī³3 ranging from +27% to +79% compared with control subjects. In patients with NSCLC, AMPK subunit protein content correlated with weight loss (Ī±1, Ī±2, Ī²2 and Ī³1), fatāfree mass (Ī±1, Ī²2 and Ī³1) and fat mass (Ī±1 and Ī³1). Tumourābearing mAMPKāKiDe mice presented increased fat loss and glucose and insulin intolerance. LLC in mAMPKāKiDe mice displayed lower insulināstimulated 2āDG uptake in skeletal muscle (quadriceps: ā35%, soleus: ā49%, extensor digitorum longus: ā48%) and the heart (ā29%) than that in nonātumourābearing mice. In skeletal muscle, mAMPKāKiDe abrogated the tumourāinduced increase in insulināstimulated TBC1D4thr642 phosphorylation. The protein content of TBC1D4 (+26%), pyruvate dehydrogenase (PDH; +94%), PDH kinases (+45% to +100%) and glycogen synthase (+48%) was increased in skeletal muscle of tumourābearing mice in an AMPKādependent manner. Lastly, chronic AICAR treatment elevated hexokinase II protein content and normalized phosphorylation of p70S6Kthr389 (mTORC1 substrate) and ACCser212 (AMPK substrate) and rescued cancerāinduced insulin intolerance. Conclusions Protein contents of AMPK subunits were upregulated in skeletal muscle of patients with NSCLC. AMPK activation seemed protectively inferred by AMPKādeficient mice developing metabolic dysfunction in response to cancer, including AMPKādependent regulation of multiple proteins crucial for glucose metabolism. These observations highlight the potential for targeting AMPK to counter cancerāassociated metabolic dysfunction and possibly cachexia