Prevalence and Survival Impact of Pretreatment Cancer-Associated Weight Loss: A Tool for Guiding Early Palliative Care

Gannavarapu, Bhavani S.; Lau, Steven; Carter, Kristen; Cannon, Nathan A.; Gao, Ang; Ahn, Chul; Meyer, Jeffrey; Sher, David J.; Jatoi, Aminah; Infante, Rodney E.; Iyengar, Puneeth

doi:10.1200/jop.2017.025221

Cited by 58 publications

(54 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is observed in up to 50% of patients with solid tumors. 1 Cancer patients with cachexia have a >50% reduction in overall survival when compared with stage-matched patients without cachexia. 1 Even when cachexia is identified in early stage cancer patients, survival is not improved because of a potential lack of effective therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

Janus kinase inhibitors suppress cancer cachexia‐associated anorexia and adipose wasting in mice

Arora

Gupta

Guo

et al. 2020

JCSM Rapid Communications

Self Cite

View full text Add to dashboard Cite

Background Cachexia, a syndrome of muscle atrophy, adipose loss, and anorexia, is associated with reduced survival in cancer patients. The colon adenocarcinoma C26c20 cell line secretes the cytokine leukaemia inhibitory factor (LIF), which induces cachexia. We characterized how LIF promotes cachexia-associated weight loss and anorexia in mice through Janus kinase (JAK)dependent changes in adipose and hypothalamic tissues. Methods Cachexia was induced in vivo with the heterotopic allotransplanted administration of C26c20 colon adenocarcinoma cells or the intraperitoneal administration of recombinant LIF in the absence or presence of JAK inhibitors. Blood, adipose, and hypothalamic tissues were collected and processed for cytokine/adipokine enzyme-linked immunosorbent assays, immunoblot analysis, and quantitative reverse transcription polymerase chain reaction (RT-PCR). Cachexia-associated lipolysis was induced in vitro by stimulating differentiated adipocytes with recombinant LIF or interleukin (IL)-6 in the absence or presence of lipase or JAK inhibitors. These adipocytes were processed for glycerol release into the media, immunoblot analysis, and RT-PCR. Results Tumour-secreted LIF induced changes in adipose tissue expression and serum levels of IL-6 and leptin in a JAK-dependent manner influencing cachexia-associated adipose wasting and anorexia. We identified two JAK inhibitors that block IL-6 family-mediated adipocyte lipolysis and IL-6 induction using an in vitro cachexia lipolysis assay. JAK inhibitors administered to the in vivo C26c20 cancer cachexia mouse models led to (i) a decrease in signal transducer and activator of transcription 3 phosphorylation in hypothalamic and adipose tissues, (ii) a reverse in the cachexia serum cytokine/adipokine signature, (iii) a delay in cancer cachexia-associated anorexia and adipose loss, and (iv) an improvement in overall survival. Conclusions JAK inhibitors suppress LIF-associated adipose loss and anorexia in both in vitro and in vivo models of cancer cachexia.

show abstract

Section: Introductionmentioning

confidence: 99%

Janus kinase inhibitors suppress cancer cachexia‐associated anorexia and adipose wasting in mice

Arora

Gupta

Guo

et al. 2020

JCSM Rapid Communications

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is observed in up to 50% of patients with solid tumors. 1 Cancer patients with CX have greater than a 50% reduction in overall survival when compared to stage matched patients without cachexia. 1 Even when CX is identified in early stage cancer patients, survival is not improved because of a potential lack of effective therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

“…1 Cancer patients with CX have greater than a 50% reduction in overall survival when compared to stage matched patients without cachexia. 1 Even when CX is identified in early stage cancer patients, survival is not improved because of a potential lack of effective therapeutic interventions. 2 Although CX has been recognized for more than half a century, most preclinical studies and clinical trials targeting the immune system (TNF-α, IL-6), appetite stimulation, and muscle regeneration have failed to durably improve the syndrome.…”

Section: Introductionmentioning

confidence: 99%

JAK Inhibitors Suppress Colon Cancer Cachexia-Associated Anorexia and Adipose Wasting in Mice

Arora

Gupta

Guo

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Abbreviations: CX, cachexia; IL-6, interleukin 6; JAK, janus kinase; LIF, leukemia inhibitory factor; rLIF, recombinant leukemia inhibitory factor; STAT3, signal transducer and activator of transcription 3. ABSTRACTBackground: Cachexia (CX), a syndrome of muscle atrophy, adipose loss, and anorexia, is associated with reduced survival in cancer patients. The colon adenocarcinoma C26c20 cell line secretes the cytokine leukemia inhibitor factor (LIF) which induces CX. We characterized how LIF promotes CX-associated weight loss and anorexia in mice through JAK-dependent changes in adipose and hypothalamic tissues.Methods: CX was induced in vivo with C26c20 colon adenocarcinoma cells or recombinant LIF administration in the absence or presence of JAK inhibitors. Blood, adipose, and hypothalamic tissues were collected and processed for cyto/adipokine ELISAs, immunoblot analysis, and quantitative RT-PCR. CX was induced in vitro by stimulating differentiated adipocytes with recombinant LIF or IL-6 in the absence or presence of lipase or JAK inhibitors. These activated adipocytes were processed for lipolysis, immunoblot analysis, and RT-PCR.Results: Tumor-secreted LIF induced changes in adipose tissue expression and serum levels of IL-6 and leptin in a JAK-dependent manner influencing CX-associated adipose wasting and anorexia. We identified two JAK inhibitors that block cytokine-mediated adipocyte lipolysis and IL-6 induction using an in vitro CX lipolysis assay. JAK inhibitors administered to in vivo colon cancer CX mouse models led to 1) a decrease in STAT3 phosphorylation in hypothalamic and adipose tissues, 2) a reverse in the CX serum cyto/adipokine signature, 3) a delay in colon cancer CX-associated anorexia and adipose loss, and 4) an improvement in overall survival. Conclusions: JAK inhibitors suppress cytokine-associated adipose loss and anorexia in multiple in vitroand in vivo models of cancer CX.

show abstract

“…Involuntary weight loss is a common occurrence among patients with cancer and is often a precursor to cancer diagnosis. In a study by Gannavarapu et al, cancer‐associated weight loss was observed in 34.1% of patients at the time of cancer diagnosis . Because of this early and often prolonged weight loss, it is important to obtain a detailed weight history and evaluate whether the weight loss was indeed intentional as a result of diet or lifestyle interventions, as may be initially reported by the patient, or in fact unintentional and due to other factors.…”

Section: Oncology Patient Populationmentioning

confidence: 99%

Using Global Criteria to Detect Malnutrition: Application in Disease States

2019

View full text Add to dashboard Cite

The accurate diagnosis and subsequent treatment of malnutrition is an essential component of nutrition care because of the known negative impacts of malnutrition on patient outcomes. The detection of malnutrition is influenced by disease-specific characteristics, practice settings, and the availability of resources. This article explores how malnutrition diagnosis through the application of the Global Leadership Initiative on Malnutrition global consensus on malnutrition diagnostic criteria is impacted by the unique characteristics of the heart failure, oncology, and trauma populations. (Nutr Clin Pract. 2020;35:85-97)

show abstract

Prevalence and Survival Impact of Pretreatment Cancer-Associated Weight Loss: A Tool for Guiding Early Palliative Care

Cited by 58 publications

References 20 publications

Janus kinase inhibitors suppress cancer cachexia‐associated anorexia and adipose wasting in mice

Janus kinase inhibitors suppress cancer cachexia‐associated anorexia and adipose wasting in mice

JAK Inhibitors Suppress Colon Cancer Cachexia-Associated Anorexia and Adipose Wasting in Mice

Using Global Criteria to Detect Malnutrition: Application in Disease States

Contact Info

Product

Resources

About