title: Skeletal muscle apoptosis is not increased in gastric cancer patients with mild-moderate weight loss.
abstract: 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.
authors.affiliation: Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore Largo A.Gemelli, 8, 00168 Rome, Italy. maubosso@tin.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bossola
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mirabella
authors.forename: Enzo
authors.initials: E
authors.lastname: Ricci
authors.forename: Paola
authors.initials: P
authors.lastname: Costelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Pacelli
authors.forename: Antonio Pio
authors.initials: AP
authors.lastname: Tortorelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Muscaritoli
authors.forename: Filippo
authors.initials: F
authors.lastname: Rossi Fanelli
authors.forename: Francesco Maria
authors.initials: FM
authors.lastname: Baccino
authors.forename: Pietro Attilio
authors.initials: PA
authors.lastname: Tonali
authors.forename: Giovan Battista
authors.initials: GB
authors.lastname: Doglietto
mesh_terms: 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
chemical_list: C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1