Cancer cachexia

Dhanapal, Raghu; Saraswathi, TR; Rajkumar, GovindN

doi:10.4103/0973-029x.86670

Cited by 72 publications

(58 citation statements)

References 22 publications

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“…Morbidity and mortality from CRC invariably occurs with advanced cancers due to the progressive deterioration of normal organ function due to invasion by multiple or massive metastases (Fig. 2), as well as the development of acute complications or extensive and com plete wasting/ degradation of the patient in a process called cachexia [23]. Essentially, cancer lethality arises from the spread of primary tumours to secondary sites where these induce critical organ failure resulting in patient death.…”

Section: Introductionmentioning

confidence: 99%

Integrin αvβ6 sets the stage for colorectal cancer metastasis

Cantor

Cheruku

Nice

et al. 2015

Cancer Metastasis Rev

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The β6 subunit of the αvβ6 integrin heterodimer has long been an enigma in cancer biology though recent research has provided many new insights into its biology. Collectively, these findings include discovery of the transcriptional, translational and cell biological mechanisms by which β6 acts, the identification of the cellular influences β6 exerts upon the cell proteome, the characterisation of multiple β6-centric pro-metastatic signalling systems and the search for pharmacological therapies (industry and academia) targeted against β6. Once expressional restriction is overcome in early colorectal cancer (CRC), epithelial cell surface restricted αvβ6 can physically interact with, and activate, known oncoproteins, and has the potential to enable the cross-talk through non-canonical signal transduction pathways, resulting in the adoption of an invasive/metastatic phenotype. This recent research has identified numerous interconnections and potential feedback loops, highlighting the fact that the expression of the β6 subunit may initiate a cascade of downstream effects on the CRC cell rather than acting through a single mechanism. We here review these recent studies and postulate that the existence of a cell surface uPAR/αvβ6/TGFβ "metastasome" interactome in/on a proportion of colorectal cancer cells, where β6 expression sequesters and activates multiple systems at the invasive front of tumour lesions, promoting cancer metastasis and hence explaining why β6 has been correlated with reduced patient survival in CRC.

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Section: Introductionmentioning

confidence: 99%

Integrin αvβ6 sets the stage for colorectal cancer metastasis

Cantor

Cheruku

Nice

et al. 2015

Cancer Metastasis Rev

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“…Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass that affects up to 80% of cancer patients, depending on the cancer type [1], and it represents the direct cause of at least 20% of cancer deaths [2]. The muscle wasting in cancer patients leads to a significant weight loss that affects the quality of life, response to radio-and chemotherapy, tolerance to treatment, and survival [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-mRNA Co-sequencing Identifies Transcriptional and Post-transcriptional Regulatory Networks Underlying Muscle Wasting in Cancer Cachexia

Fernández¹,

Ferreira²,

Vechetti³

et al. 2019

Preprint

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Cachexia is a complex metabolic syndrome characterized by loss of skeletal muscle, leading to a significant weight loss that impacts patient morbidity and mortality. Given the complexity of gene regulatory networks that control gene expression, our objective was to perform an integrative mRNA and miRNA profiling to identify genetic programs that capture essential mechanistic details that promote muscle atrophy in cancer cachexia. Here, we used RNA sequencing to analyze miRNAs and mRNAs expression profiles in tibialis anterior (TA) muscles of the Lewis lung carcinoma model of cancer cachexia. In addition, we compared these findings with RNA-Seq data from C2C12 myotubes treated in vitro with the cachectic factors tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Extracellular matrix (ECM) alterations were validated by picrosirius staining, western blot, and fractal dimension analyses. We found 1,008 mRNAs and 18 miRNAs differentially expressed in cachectic mice. This set of genes was associated with the ECM, proteolysis, and inflammatory response. Enrichment analysis of transcriptional factor binding sites revealed activation of the atrophy-related transcriptional factors: NF-κB, Stat3, AP-1, and FoxO. Furthermore, the integration of mRNA and miRNA expression profiles identified posttranscriptional regulation by miRNAs of genes involved in ECM organization, cell migration, transcription factors binding, ion transport, and FoxO signaling pathway. C2C12 myotubes treated with TNF-α and IFN-γ similarly down-regulate subsets of ECM genes, including collagens. Our integrative analysis of miRNA-mRNA co-profiles comprehensive characterized regulatory relationships of molecular pathways and revealed miRNAs targeting ECM-associated genes in cancer cachexia. We also confirmed in C2C12 myotubes that changes in ECM-associated genes are dependent on inflammatory signaling of the cytokines TNF-α and IFN-γ.

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“…When dehydration occurs, renal failure and other adverse effects such as constipation are common, which can associate with impaired mental status and delirium . Mechanical obstructive tumors can lead to weight loss and shorter survival times …”

Section: Introductionmentioning

confidence: 99%

“…22,[26][27][28][29] Mechanical obstructive tumors can lead to weight loss and shorter survival times. [30][31][32] Within certain cancer populations, dysphagia is highly prevalent:…”

Section: Introductionmentioning

confidence: 99%

Development and evaluation of screening dysphagia tools for observational studies and routine care in cancer patients

Borean

Shani

Brown

et al. 2018

Health Science Reports

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Background and aimsDysphagia can be associated with significant morbidity in cancer patients. We aimed to develop and evaluate dysphagia screener tools for use in observational studies (phase 1) and for routine symptom monitoring in clinical care (phase 2).MethodsVarious dysphagia or odynophagia screening questions, selected after an expert panel reviewed the content, criterion, and construct validity, were compared with either functional assessment of cancer therapy ‐ esophageal cancer (FACT‐E) Swallowing Index Cut‐Off Values or to questions adapted from the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events. Sensitivity, specificity, and patient acceptability were assessed.ResultsIn Phase 1 (n = 178 esophageal cancer patients), the screening question “How are you currently eating?” had the highest sensitivities and specificities against various Swallowing Index Cut‐Off Value cut‐offs, with the best optimal cutoff associated with weight loss (80% sensitivity and 75% specificity). In phase 2 (255 head and neck, gastro‐esophageal, and thoracic cancer patients), a single question screener (“Do you experience any difficulty or pain upon swallowing?”) versus a Patient Reported Outcomes for Common Terminology Criteria for Adverse Events–like gold standard generated sensitivities between 86% and 94% and specificities between 93% and 100%. This screening question (+/− follow‐up questions) had a median completion time of under 2 minutes, and >90% of patients were willing to complete the survey electronically, did not feel that survey made clinic visit more difficult, and did not find the questions upsetting or distressful.ConclusionOur results demonstrate that these screener tools (“How are you currently eating?”, “Do you experience any difficulty or pain upon swallowing?”) can effectively screen dysphagia symptoms without increasing cancer outpatient clinic burden, both in observational studies and for routine clinical monitoring.

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Cancer cachexia

Cited by 72 publications

References 22 publications

Integrin αvβ6 sets the stage for colorectal cancer metastasis

Integrin αvβ6 sets the stage for colorectal cancer metastasis

MicroRNA-mRNA Co-sequencing Identifies Transcriptional and Post-transcriptional Regulatory Networks Underlying Muscle Wasting in Cancer Cachexia

Development and evaluation of screening dysphagia tools for observational studies and routine care in cancer patients

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