Skeletal muscle apoptosis is not increased in gastric cancer patients with mild-moderate weight loss.
Numerous experimental and clinical studies have shown that skeletal muscle apoptotis may increase in wasting conditions and suggest that apoptosis might contribute to the loss of lean body mass. Data in cancer patients are still lacking. The present study aimed at verifying whether apoptosis was enhanced in the skeletal muscle of 16 patients with gastric cancer with respect to controls. A biopsy specimen was obtained from the rectus abdominis muscle. The occurrence of apoptosis in muscle biopsies was determined morphologically by the fluorescent transferase-mediated dUTP nick end labeling assay and by immunohistochemistry for caspase-3 and caspase-1. Mean weight loss was 6+/-2% in cancer patients and 0.5+/-0.1% in controls (p<0.0001). Serum albumin levels (g/dL) were 3.7+/-0.3 in cancer patients and 4.1+/-0.2 in controls (p<0.05). The percentage of apoptotic myonuclei was similar in cancer patients and in controls (1.5+/-0.3 versus 1.4+/-0.2, respectively; p=ns), in gastric cancer patients with mild (1.6+/-0.4) or moderate-severe weight loss (1.4+/-0.5) (p=ns), and in the different stages of disease (stages I-II: 1.5+/-0.7; stage III: 1.3+/-0.4; stage IV: 1.6+/-0.3; p=ns). By immunohistochemistry, caspase-1 and caspase-3 positive fibers were absent in controls and in neoplastic patients. Poly-ADP-ribosyl polymerase, a typical caspase-3 substrate whose processing is indicative of caspase-3 activation, was not cleaved in muscle biopsies of cancer patients. These data suggest that skeletal muscle apoptosis is not increased in neoplastic patients with mild-moderate weight loss and argue against the hypotheses that caspase-3 activation might be an essential step of myofibrillar proteolysis in cancer-related muscle wasting.
Bossola
Maurizio
M
Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore Largo A.Gemelli, 8, 00168 Rome, Italy. maubosso@tin.it
Mirabella
Massimiliano
M
Ricci
Enzo
E
Costelli
Paola
P
Pacelli
Fabio
F
Tortorelli
Antonio Pio
AP
Muscaritoli
Maurizio
M
Rossi Fanelli
Filippo
F
Baccino
Francesco Maria
FM
Tonali
Pietro Attilio
PA
Doglietto
Giovan Battista
GB
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001706:Biopsy; D020170:Caspase 1 / Q000032:analysis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology*; D017568:Rectus Abdominis / Q000473:pathology; D013274:Stomach Neoplasms / Q000503:physiopathology*; D019282:Wasting Syndrome / Q000503:physiopathology; D015431:Weight Loss / Q000502:physiology
C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1