Activity level, apoptosis, and development of cachexia in ApcMin/+ mice

Baltgalvis, Kristen A.; Berger, Franklin G.; Peña, Maria Marjorette O.; Davis, John M.; White, James P.; Carson, James A.

doi:10.1152/japplphysiol.00442.2010

Cited by 65 publications

(101 citation statements)

References 32 publications

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“…The role of Fis1 during wasting diseases is currently unknown, but Fis1 overexpression is proapoptotic (29,31,43). Apoptosis in skeletal muscle is commonly observed during cancer cachexia (10,22), and we have also seen apoptosis induced in cachectic Apc Min/ϩ mouse hindlimb muscle (7). In the Apc Min/ϩ mouse, muscle Fis1 expression may be inducing apoptosis providing an additional mechanism for linking muscle mass loss to mitochondrial content.…”

Section: Discussionmentioning

confidence: 57%

“…The inherent variability in cachexia development between mice is a strength of the Apc Min/ϩ mouse model, and Apc Min/ϩ mice cachexia symptom severity was assigned at the study's end as in previously published studies (6,7). Mice were classified as having mild, moderate, or severe cachexia based on their body mass, gastrocnemius muscle mass, and epididymal fat pad mass.…”

Section: Animals All Wt and Apcmentioning

confidence: 99%

See 1 more Smart Citation

Muscle oxidative capacity during IL-6-dependent cancer cachexia

White

Baltgalvis

Puppa

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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134

204

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Many diseases are associated with catabolic conditions that induce skeletal muscle wasting. These various catabolic states may have similar and distinct mechanisms for inducing muscle protein loss. Mechanisms related to muscle wasting may also be related to muscle metabolism since glycolytic muscle fibers have greater wasting susceptibility with several diseases. The purpose of this study was to determine the relationship between muscle oxidative capacity and muscle mass loss in red and white hindlimb muscles during cancer cachexia development in the Apc Min/+ mouse. Gastrocnemius and soleus muscles were excised from Apc Min/+ mice at 20 wk of age. The gastrocnemius muscle was partitioned into red and white portions. Body mass (−20%), gastrocnemius muscle mass (−41%), soleus muscle mass (−34%), and epididymal fat pad (−100%) were significantly reduced in severely cachectic mice ( n = 8) compared with mildly cachectic mice ( n = 6). Circulating IL-6 was fivefold higher in severely cachectic mice. Cachexia significantly reduced the mitochondrial DNA-to-nuclear DNA ratio in both red and white portions of the gastrocnemius. Cytochrome c and cytochrome- c oxidase complex subunit IV (Cox IV) protein were reduced in all three muscles with severe cachexia. Changes in muscle oxidative capacity were not associated with altered myosin heavy chain expression. PGC-1α expression was suppressed by cachexia in the red and white gastrocnemius and soleus muscles. Cachexia reduced Mfn1 and Mfn2 mRNA expression and markers of oxidative stress, while Fis1 mRNA was increased by cachexia in all muscle types. Muscle oxidative capacity, mitochondria dynamics, and markers of oxidative stress are reduced in both oxidative and glycolytic muscle with severe wasting that is associated with increased circulating IL-6 levels.

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Section: Discussionmentioning

confidence: 57%

Section: Animals All Wt and Apcmentioning

confidence: 99%

Muscle oxidative capacity during IL-6-dependent cancer cachexia

White

Baltgalvis

Puppa

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

134

204

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“…Changes in both WBC and RBC counts are characteristic in colon cancer and have been show to occur in the Apc Min/ϩ mouse (8). We therefore also performed a complete blood count to determine the role of MCP-1 on these parameters in the Apc Min/ϩ mouse.…”

Section: Discussionmentioning

confidence: 99%

“…A complete blood count was performed as both white blood cell (WBC) and red blood cell (RBC) counts have been shown to be altered during progression of intestinal tumorigenesis in this mouse model (Table 1) (8). We found that overall WBC counts were increased in Apc Min/ϩ mice (13.6 m/mm 3 Ϯ 1.8) compared with wild-type (5.7 m/mm 3 Ϯ 0.6) (P Ͻ 0.05) and MCP-1 deficiency blunted this response (7.1 m/mm 3 Ϯ 0.9) (P Ͻ 0.05).…”

Section: Complete Blood Count and Plasma Il-6mentioning

confidence: 99%

Linking tumor-associated macrophages, inflammation, and intestinal tumorigenesis: role of MCP-1

McClellan

Davis

Steiner

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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105

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Tumor-associated macrophages are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. However, its role on tumorigenesis in a genetic mouse model of colon cancer has not been explored. We examined the role of MCP-1 on tumor-associated macrophages, inflammation, and intestinal tumorigenesis. Male Apc Min/+, Apc Min/+/MCP-1−/− or wild-type mice were euthanized at 18 wk of age and intestines were analyzed for polyp burden, apoptosis, proliferation, β-catenin, macrophage number and phenotype, markers for cytotoxic T lymphocytes and regulatory T cells, and inflammatory mediators. MCP-1 deficiency decreased overall polyp number by 20% and specifically large polyp number by 45% ( P < 0.05). This was consistent with an increase in apoptotic cells ( P < 0.05), but there was no change detected in proliferation or β-catenin. MCP-1 deficiency decreased F4/80-positive cells in both the polyp tissue and surrounding intestinal tissue ( P < 0.05) as well as expression of markers associated with M1 (IL-12 and IL-23) and M2 macrophages (IL-13, CD206, TGF-β, and CCL17) ( P < 0.05). MCP-1 knockout was also associated with increased cytotoxic T lymphocytes and decreased regulatory T cells ( P < 0.05). In addition, MCP-1−/− offset the increased mRNA expression of IL-1β and IL-6 in intestinal tissue and IL-1β and TNF-α in polyp tissue ( P < 0.05), and prevented the decrease in SOCS1 expression ( P < 0.05). We demonstrate that MCP-1 is an important mediator of tumor growth and immune regulation that may serve as an important biomarker and/or therapeutic target in colon cancer.

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“…The weight loss observed in some models is coincident with electrophysiological muscle fatigue (Aulino et al, 2010; Baltgalvis et al, 2010; Murphy et al, 2012; Norden et al, 2014), reduced locomotor activity (Lamkin et al, 2011; Murphy et al, 2012; Xiu et al, 2010), and reduced voluntary wheel running (Baltgalvis et al, 2010; Wood et al, 2006). Reduced locomotor activity may reflect fatigue or physical limitations due to the tumor location and/or changes in areas of the CNS that regulate movement (Dantzer et al, 2012).…”

Section: Rodent Models Of Cancermentioning

confidence: 99%

Pre-treatment effects of peripheral tumors on brain and behavior: Neuroinflammatory mechanisms in humans and rodents

Schrepf¹,

Lutgendorf²,

Pyter³

2015

Brain, Behavior, and Immunity

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Cancer patients suffer high levels of affective and cognitive disturbances, which have been attributed to diagnosis-related distress, impairment of quality of life, and side effects of primary treatment. An inflammatory microenvironment is also a feature of the vast majority of solid tumors. However, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and cognitive disturbances. In this review, we summarize the burgeoning evidence from rodent cancer models that solid tumors alter neurobiological pathways and subsequent behavioral processes with relevance to affective and cognitive disturbances reported in human cancer populations. We consider, in parallel, the evidence from human clinical cancer research demonstrating that affective and cognitive disturbances are common in some malignancies prior to diagnosis and treatment. We further consider the underlying neurobiological pathways, including altered neuroinflammation, tryptophan metabolism, prostaglandin synthesis and associated neuroanatomical changes, that are most strongly implicated in the rodent literature and supported by analogous evidence from human cancer populations. We focus on the implications of these findings for behavioral researchers and clinicians, with particular emphasis on methodological issues and areas of future research.

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Activity level, apoptosis, and development of cachexia in Apc^Min/+ mice

Cited by 65 publications

References 32 publications

Muscle oxidative capacity during IL-6-dependent cancer cachexia

Muscle oxidative capacity during IL-6-dependent cancer cachexia

Linking tumor-associated macrophages, inflammation, and intestinal tumorigenesis: role of MCP-1

Pre-treatment effects of peripheral tumors on brain and behavior: Neuroinflammatory mechanisms in humans and rodents

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