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Biomedical subjects

M D Barber

Publications and source records attributed to M D Barber.

At least 37 records · Page 2Linked to original sources
PubMed2000

Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor.

BACKGROUND: Recently a novel tumour-derived cachectic factor was identified in the murine MAC16 colonic adenocarcinoma model of cachexia. This factor, provisionally named proteolysis-inducing factor (PIF), was subsequently identified in the urine of weight-losing patients with cancer but not in the urine of weight-stable patients with cancer or weight-losing controls with benign disease. This study determined the nutritional characteristics of patients with pancreatic cancer who excrete PIF in the urine and investigated the relationship between PIF and the acute-phase protein response. METHODS: PIF was isolated from urine by precipitation and ultrafiltration and was then identified by Western blotting of nitrocellulose membranes using a previously developed monoclonal antibody. Full nutritional assessment of patients was undertaken at the same time as urine collection. RESULTS: PIF was detected in the urine of 80 per cent of patients (n = 55). These patients had a significantly greater total weight loss and rate of weight loss than patients whose urine did not contain PIF (median 12.5 (range 4-43) kg versus 4.5 (0-14) kg; P < 0.0002). No association was evident between the presence of PIF in patients' urine and serum C-reactive protein (CRP) concentration. Furthermore, the accelerated weight loss associated with PIF expression also appeared to be independent of the acute-phase response. Overall the presence of PIF was not associated with reduced survival, although the previously reported association between raised CRP concentration and poor prognosis was confirmed. CONCLUSION: PIF is associated with an accelerated rate of weight loss in patients with a tumour of the pancreatic head. This observation appears to be independent of the effect of an increased hepatic acute-phase protein response.

Aged↗
PubMed2000

A polymorphism of the interleukin-1 beta gene influences survival in pancreatic cancer.

Pro-inflammatory cytokines contribute to the cachexia associated with pancreatic cancer and stimulate the acute phase response which has been associated with shortened survival in such patients. Polymorphisms of cytokine genes may influence their production. The present study examined the effect of a polymorphism of the interleukin (IL)-1b gene upon the inflammatory state and survival in pancreatic cancer. Genomic DNA was obtained from 64 patients with pancreatic cancer and 101 healthy controls. Using the polymerase chain reaction and subsequent TaqI restriction enzyme digestion the subject's genotype for a diallelic polymorphism of the interleukin-1b gene was established. IL-1b production by peripheral blood mononuclear cells and serum C-reactive protein (CRP) levels from patients were also examined and survival noted. Patients homozygous for allele 2 of the IL-1b gene had significantly shorter survival than other groups (P = 0.0001). These patients also exhibited higher IL-1b production (P = 0.022). Possession of allele 2 was also associated with significantly shorter survival (median 144 vs 256 days, P = 0.034) and significantly higher CRP level (P = 0.0003). The possession of a genotype resulting in increased IL-1b production was associated with shortened survival and increased serum CRP level. This may reflect the role of IL-1b in inducing an acute phase protein response and cachexia in cancer or may be related to changes in tumour phenotype.

Adult↗
PubMed2000

Pelvic muscle electromyography of levator ani and external anal sphincter in nulliparous women and women with pelvic floor dysfunction.

OBJECTIVE: The purpose of this study was to compare results of electromyographic assessment of muscular recruitment between nulliparous control subjects without pelvic floor dysfunction and parous subjects with genuine stress urinary incontinence and with pelvic organ prolapse. Interference pattern analysis is an electromyographic technique that reproducibly measures muscular recruitment by detecting both "turns" in the electromyographic signal produced by positive and negative peaks of the motor unit potentials and motor unit potential amplitude. Fewer turns can indicate loss of motor units or failure of central activation of contraction, whereas greater amplitude can indicate reinnervation after nerve damage. STUDY DESIGN: We performed concentric needle electrode electromyographic examinations of the levator ani and external anal sphincter in 15 nulliparous control subjects and 20 parous subjects with abnormalities (n = 9 with genuine stress urinary incontinence, n = 11 with stage III or IV pelvic organ prolapse). We made digital recordings at multiple sites at rest and with moderate and maximal contraction. Interference pattern analysis yielded the number of turns per second and the mean signal amplitude (in microvolts) for each site at each contraction level. We compared individual patient data with data from the healthy population by means of cloud analysis. Mean values of number of turns per second and mean amplitude in each group were then compared with nonparametric methods and regression models. RESULTS: Mean ages were 28.7 years (range, 20-49 years) for the control group, 54.3 years (range, 35-75 years) for subjects with genuine stress urinary incontinence, and 65 years (range, 41-77 years) for subjects with pelvic organ prolapse. Median clinical levator ani strengths were 9 (range, 5-9) in the control group, 5 (range, 2-7) in the genuine stress urinary incontinence group, and 5 (range, 2-8) in the pelvic organ prolapse group. Median external anal sphincter strengths were 9 (range, 7-9) in the control group, 5 (range, 3-9) in the genuine stress urinary incontinence group, and 8 (range, 4-9) in the pelvic organ prolapse group. The external anal sphincters of subjects with pelvic organ prolapse had the highest percentage of abnormal study results according to cloud analysis. Mean number of turns per second in levators was greater in control subjects than in subjects with abnormalities (P =.034). We found similar differences in number of turns per second for the external anal sphincter (P =.004). In contrast, we did not find differences between groups in mean amplitude in either the levator ani or the external anal sphincter. Comparison of patients with genuine stress urinary incontinence versus subjects with pelvic organ prolapse showed no significant difference in the number of turns per second in either muscle. Mean amplitude was greater in the pelvic organ prolapse group than in the genuine stress urinary incontinence group for both muscles (levator ani, P =.028; external anal sphincter, P =.048). Neither mean amplitude nor the number of turns per second could be predicted by clinically estimated levator ani strength, age, or fecal incontinence. CONCLUSION: Compared with nulliparous control subjects, patients with genuine stress urinary incontinence and pelvic organ prolapse had changes in the levator ani and external anal sphincter consistent with either motor unit loss or failure of central activation, or both. Subjects with pelvic organ prolapse had findings consistent with greater recovery than was found in those with genuine stress urinary incontinence. Measures of recruitment by interference pattern analysis correlated better with clinical external anal sphincter strength than with levator ani strength and were independent of age.

Adult↗
PubMed2000

Bilateral uterosacral ligament vaginal vault suspension with site-specific endopelvic fascia defect repair for treatment of pelvic organ prolapse.

OBJECTIVE: The anatomic and functional success of suspension of the vaginal cuff to the proximal uterosacral ligaments is described. STUDY DESIGN: Forty-six women underwent vaginal site-specific repair of endopelvic fascia defects with suspension of the vaginal cuff to the proximal uterosacral ligaments for pelvic organ prolapse. Outcome measures included operative complications, pelvic organ prolapse quantitation, and assessment of pelvic floor symptoms. RESULTS: After a median follow-up of 15.5 months (range, 3.5 months-3.4 years), 90% of patients had both resolution of vaginal bulging or prolapse symptoms and improvement of the stage of prolapse. There were improvements in all pelvic organ prolapse quantitation measurements except for total vaginal length, for which the median decrease was 0.75 cm. Intraoperatively, ureteral occlusion was noted in 11% (5/46) of patients with universal cystoscopy. In 3 patients the uterosacral suspension sutures were removed and replaced with resolution of the occlusion and in 2 patients ureteral reimplantation was required. Symptomatic prolapse (2 apical segment, 1 anterior, and 1 posterior) developed in 4 patients (10%), and 3 of them underwent reoperation. There were significant improvements in symptoms of bulging and pressure, voiding dysfunction, and vaginal and perineal splinting. CONCLUSION: Suspension of the vaginal vault to the proximal uterosacral ligaments combined with site-specific repair of endopelvic fascia defects provides excellent anatomic and functional correction of pelvic organ prolapse in most women. The risk of ureteral injury with this technique makes intraoperative cystoscopy essential.

Adult↗
PubMed2000

Liver export protein synthetic rates are increased by oral meal feeding in weight-losing cancer patients.

We have demonstrated previously that, in the fasting state, whereas albumin synthesis is similar in cachectic cancer patients compared with controls, fibrinogen synthesis is increased. Whether synthesis of these proteins is altered after an oral meal was examined in eight weight-losing pancreatic cancer patients and six healthy controls by use of an intravenous flooding dose of [(2)H(5)]- or [(2)H(8)]phenylalanine. Cancer patients had a median weight loss of 19%, a significantly lower serum albumin concentration, and a significantly higher plasma fibrinogen concentration than controls (P < 0.005). Fasting albumin synthesis rates were similar between cancer patients and controls (median total synthesis rate 11.3 vs. 13.9 g/day, respectively) and rose on feeding by a similar degree (median 29 and 24%). The fasting fibrinogen total synthetic rate was significantly higher in cancer patients than in controls (median 3.3 vs. 1.0 g/day, P = 0.0019). In cancer patients in the fed state, fibrinogen synthetic rate rose by a median of 38% (P = 0.012), whereas in controls there was no significant change. These findings demonstrate significant upregulation by feeding of acute-phase protein synthesis in cachectic cancer patients.

Adult↗
PubMed2000

Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer.

Eicosapentaenoic acid (EPA) has been shown to modulate aspects of the inflammatory response that may contribute to weight loss in cancer. This study aimed to evaluate the acceptability and effects of oral supplementation with high-purity EPA in weight-losing patients with advanced pancreatic cancer. Twenty-six patients were entered into the study. EPA (95% pure) was administered as free acid starting at 1 g/day; the dose was increased to 6 g/day over four weeks, and then a maintenance dose of 6 g/day was administered. Patients were assessed before EPA and at 4, 8, and 12 weeks while receiving EPA, for weight, body composition, hematologic and clinical chemistry variables, acute-phase protein response, and performance status. Overall survival was noted. Supplementation was well tolerated, with only five patients experiencing side effects possibly attributable to the EPA. Before starting EPA, all patients had been losing weight at a median rate of 2 kg/mo. In general, after EPA supplementation, weight was stable. After four weeks of EPA supplementation, patients had a median weight gain of 0.5 kg (p = 0.0009 vs. rate of weight loss at baseline), and this stabilization of weight persisted over the 12-week study period. Total body water as a percentage of body weight remained stable, as did the proportion of patients with an acute-phase protein response, patients' nutritional intake, and performance status. Overall median survival from diagnosis in this study was 203 days. This study suggests that EPA is well tolerated, may stabilize weight in cachectic pancreatic cancer patients, and should be tested as an anticachectic agent in controlled trials.

Adenocarcinoma↗
PubMed2000

Metabolic response to feeding in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement.

Weight-losing patients with advanced cancer often fail to gain weight with conventional nutritional support. This suboptimal response might be explained, in part, by an increased metabolic response to feeding. It has been suggested that eicosapentaenoic acid (EPA) can modify beneficially the metabolic response to cancer. The aim of the present study was to examine the metabolic response to feeding in cancer and the effects of an EPA-enriched oral food supplement on this response. A total of 16 weight-losing, non-diabetic patients with unresectable pancreatic adenocarcinoma and six healthy, weight-stable controls were studied by indirect calorimetry in the fasting and fed states. Body composition was estimated by bioimpedence analysis. Cancer patients were then given a fish-oil-enriched nutritional supplement providing 2 g of EPA and 2550 kJ daily, and underwent repeat metabolic study after 3 weeks of such supplementation. At baseline, resting energy expenditure whether expressed per kg body weight, lean body mass or body cell mass was significantly greater in the cancer patients compared with controls. Fat oxidation was significantly higher in the fasting state in cancer patients [median 1.26 g.kg(-1).min(-1) (interquartile range 0.95-1.38)] than in controls [0.76 g.kg(-1). min(-1) (0.62-0.92); P<0.05]. Over the 4 h feeding period, changes in insulin and glucose concentrations in cancer patients suggested relative glucose intolerance. In response to oral meal feeding, the percentage change in the area under the curve of energy expenditure was significantly lower in the cancer patients [median 7.9% (interquartile range 3.4-9.0)] than in controls [12.6% (9.9-15.1); P<0.01]. After 3 weeks of the EPA-enriched supplement, the body weight of the cancer patients had increased and the energy expenditure in response to feeding had risen significantly [9.6% (6. 3-12.4)], such that it was no different from baseline healthy control values. Similarly, fasting fat oxidation fell to 1.02 g. kg(-1).min(-1) (0.8-1.18), again no longer significantly different from baseline healthy control values. While weight-losing patients with advanced pancreatic cancer have an increased resting energy expenditure and increased fat oxidation, the energy cost of feeding is, in fact, reduced. Provision of a fish-oil-enriched nutritional supplement results in some normalization of the metabolic response in both the fasted and fed states, in association with an improvement in nutritional status.

Aged↗
PubMed1999

Pancreatic cancer as a model: inflammatory mediators, acute-phase response, and cancer cachexia.

Patients with pancreatic cancer frequently develop the syndrome of cancer cachexia. Pro-inflammatory cytokines have been strongly implicated in the pathogenesis of this syndrome. In patients with pancreatic cancer an acute-phase response (an index of pro-inflammatory cytokine activity) is associated with accelerated weight loss, hypermetabolism, anorexia, and a shortened duration of survival. However, little is known about the primary significance of the acute-phase response in terms of altered hepatic export protein synthesis rates and its potential impact on the body's nitrogen economy. In a recent series of studies on weight-losing pancreatic cancer patients with hypoalbuminemia we have demonstrated albumin synthesis to be unaltered whereas fibrinogen synthesis is increased two- to threefold compared with healthy controls. Because of the mismatch in amino acid composition between the body's main labile amino acid reserve (skeletal muscle) and that of acute-phase proteins, these results lend support to the concept that in pancreatic cancer the reprioritization of body protein metabolism during an acute-phase response may well be a significant factor in the loss of lean tissue in these patients.

Acute-Phase Proteins↗
PubMed1999

Accuracy of clinical assessment of paravaginal defects in women with anterior vaginal wall prolapse.

OBJECTIVE: The objective of this study was to determine the accuracy of clinical assessment of paravaginal defects in women with anterior vaginal wall prolapse. STUDY DESIGN: A retrospective chart review of all women undergoing surgery for anterior vaginal wall prolapse during the years of 1994 to 1996 identified operative notes that described the surgical assessment of paravaginal support. These surgical findings were compared with the preoperative clinical assessment. Clinical parameters that predicted poor correlation were identified. Statistical analysis used the chi(2) test. RESULTS: One hundred seventeen patients had surgery for anterior vaginal prolapse. Seventy had documentation of an intraoperative paravaginal support evaluation. Of these, 44 patients had vaginal procedures, and 26 had abdominal procedures. All patients had at least stage 2 prolapse before surgery, and all were noted to have excellent pelvic support 4 to 6 weeks after surgery. The prevalence of paravaginal defects at surgery was 47% on the right and 41% on the left. The sensitivity and negative predictive value for the clinical assessment for paravaginal defects were good on both the right and left sides, whereas the specificity and positive predictive values were poor. Stage of prolapse, previous hysterectomy, or previous anterior colporrhaphy did not significantly affect the accuracy of the clinical examination in predicting fascial defects. However, previous retropubic urethropexy did significantly decrease the accuracy of the clinical examination in predicting right paravaginal defects (P <.01) but not left. CONCLUSION: Although preoperative clinical assessment for paravaginal defects is useful, it does not substitute for careful intraoperative evaluation for endopelvic fascial defects.

Adult↗
PubMed1999

Cancer cachexia.

Cachexia is a common cause of morbidity and mortality in patients with advanced cancer. It is characterised by numerous metabolic abnormalities including inefficient substrate utilisation, alterations in the balance of energy intake and expenditure and the acute-phase protein response. These changes seem to be driven by pro-inflammatory cytokines, alterations of the neuro-endocrine axis and tumour-derived catabolic factors. This results in the loss of both fat and lean tissue. Trials of conventional nutritional supplements in patients with cancer cachexia have failed to show any benefit in terms of weight gain or quality of life and this may be because the ongoing metabolic abnormalities prevent the efficient use of additional calories supplied. A variety of pharmacological agents have been studied in an attempt to normalise these metabolic changes with only limited success. However, it is possible that the combination of an agent to normalise the metabolic milieu along with the provision of additional nutritional support may have the potential to reverse cachexia in advanced cancer.

Anti-Inflammatory Agents↗
PubMed1999

The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer.

Previous studies have suggested that administration of oral eicosapentaenoic acid (EPA) will stabilize weight in patients with advanced pancreatic cancer. The aim of the present study was to determine if a combination of EPA with a conventional oral nutritional supplement could produce weight gain in these patients. Twenty patients with unresectable pancreatic adenocarcinoma were asked to consume two cans of a fish oil-enriched nutritional supplement per day in addition to their normal food intake. Each can contained 310 kcal, 16.1 g protein and 1.09 g EPA. Patients were assessed for weight, body composition, dietary intake, resting energy expenditure (REE) and performance status. Patients consumed a median of 1.9 cans day(-1). All patients were losing weight at baseline at a median rate of 2.9 kg month(-1). After administration of the fish oil-enriched supplement, patients had significant weight-gain at both 3 (median 1 kg, P= 0.024) and 7 weeks (median 2 kg, P = 0.033). Dietary intake increased significantly by almost 400 kcal day(-1) (P = 0.002). REE per kg body weight and per kg lean body mass fell significantly. Performance status and appetite were significantly improved at 3 weeks. In contrast to previous studies of oral conventional nutritional supplements in weight-losing cancer patients, this study suggests that an EPA-enriched supplement may reverse cachexia in advanced pancreatic cancer.

Adenocarcinoma↗
PubMed1999

Two polymorphisms of the tumour necrosis factor gene do not influence survival in pancreatic cancer.

Polymorphisms of the tumour necrosis factor (TNF) gene have been related to TNF production and outcome in a variety of inflammatory and malignant diseases. Proinflammatory cytokines and the inflammatory state appear to affect outcome in pancreatic cancer. Thus, the present study examined the TNFB and TNF-308 polymorphisms for their relationship to the inflammatory state and survival in pancreatic cancer. Sixty-four patients with advanced pancreatic cancer and 101 healthy subjects were genotyped for each polymorphism. Serum concentrations of the two TNF receptors and C-reactive protein (CRP) were measured in 45 of the cancer patients with no evidence of infection or jaundice, 1 month after surgical intervention. There was no difference in distribution of genotypes between the patient and control groups. There was no association between any genotype and concentrations of any of the measured inflammatory mediators. While those with an elevated CRP concentration had significantly poorer survival, there was no association between either TNF genotype and survival. This study found no association between TNF genotype and the inflammatory state or survival in advanced pancreatic cancer. Other cytokines may be more important than TNF in determining the inflammatory state and disease progress in pancreatic cancer.

Adult↗
PubMed1999

Fish oil-enriched nutritional supplement attenuates progression of the acute-phase response in weight-losing patients with advanced pancreatic cancer.

The presence of an acute-phase protein response (APPR) has been suggested to shorten survival and contribute to weight loss in patients with pancreatic cancer. Fatty acids derived from fish oil have been shown to alter proinflammatory cytokine production and acute-phase protein synthesis in vitro. The present study was designed to determine the effects of a fish oil-enriched nutritional supplement on the concentrations of a range of individual acute-phase proteins (APP) in patients with advanced pancreatic cancer. In a sequential series, 18 patients with pancreatic cancer received the supplement (providing 2 g eicosapentaenoic acid and 1 g docosahexaenoic acid/d) for 3 wk while another 18 received full supportive care alone. Six healthy subjects served as additional controls. Acute-phase proteins were measured before and after the 3-wk intervention period in cancer patients. At baseline, albumin, transferrin and pre-albumin were significantly reduced and fibrinogen, haptoglobin, alpha-1-acid glycoprotein, alpha-1-antitrypsin, ceruloplasmin and C-reactive protein (CRP) were significantly elevated in the cancer patients compared with healthy controls, reflecting their roles as negative and positive acute phase proteins, respectively. In the supplemented cancer group, the only significant change in APP concentrations over the 4-wk study period was an increase in transferrin. In the control cancer group there were further significant reductions in albumin, transferrin and pre-albumin, and a significant increase in CRP concentration. These results suggest that many positive and negative APP are altered in advanced pancreatic cancer. The APPR tends to progress in untreated patients but may be stabilized by the administration of a fish oil-enriched nutritional supplement. This may have implications for reducing wasting in such patients.

Acute-Phase Proteins↗
PubMed1999

Changes in nutritional, functional, and inflammatory markers in advanced pancreatic cancer.

Weight loss and the acute-phase response have been associated with poor quality of life and survival in advanced pancreatic cancer; however, little information is available on changes in these factors over time and their interrelationships. This study examined changes in weight, Karnofsky performance status, C-reactive protein (CRP), and serum albumin in 25 patients with advanced pancreatic cancer given supportive symptomatic treatment only. Patients were assessed at approximately monthly intervals on a total of 70 occasions, allowing assessment of changes over 37 intervals. Overall, patients had a median weight loss of 2.3 kg/28 days. Median CRP levels rose by 15 mg/l, and serum albumin fell by 1 g/l on average over 28 days. Karnofsky performance status fell by 4 points every 28 days. The nine patients assessed close to death were compared with the 13 assessed close to diagnosis. The increase in CRP level and fall in weight and performance status were significantly greater within eight weeks of death than within eight weeks of diagnosis. Among patients close to diagnosis, 13% had an elevated CRP compared with 100% of those close to death. In multivariate analysis, Karnofsky performance status was significantly associated with percent weight loss and CRP levels. These data further implicate the acute-phase protein response as being associated with the progressive weight loss seen in patients with advanced pancreatic cancer. Changes appear to accelerate close to death. Moreover, the development of cachexia is associated with a reduction in patients' functional capacity.

Adult↗
PubMed1999

Relationship of serum levels of interleukin-6, soluble interleukin-6 receptor and tumour necrosis factor receptors to the acute-phase protein response in advanced pancreatic cancer.

The level of the acute-phase response is a major predictor of survival in patients with advanced pancreatic cancer. This study examines the association between the acute-phase protein response, as determined by serum C-reactive protein, and serum levels of interleukin-6, soluble interleukin-6 receptor and the soluble tumour necrosis factor receptors in patients with pancreatic cancer. Thirty-four blood samples were collected from 13 patients with advanced pancreatic cancer. Samples were also collected from six healthy subjects. Levels of C-reactive protein, interleukin-6, soluble interleukin-6 receptor and soluble tumour necrosis factor receptors 55 and 75 were measured by indirect ELISA. Serum levels of C-reactive protein, interleukin-6 and soluble tumour necrosis factor receptors 55 and 75 were significantly higher in cancer patients than in controls. Levels of serum soluble interleukin-6 receptor were not significantly different between the two groups. In cancer patients, a significant positive association was found between the level of the acute-phase protein response and serum levels of interleukin-6, soluble tumour necrosis factor receptor 55 and soluble tumour necrosis factor receptor 75. No association was found between levels of soluble interleukin-6 receptor and any other factor. There is no significant relationship between the level of soluble interleukin-6 receptor and the acute-phase protein response in vivo and the biological role of soluble interleukin-6 receptor in the chronic inflammatory component of cachexia remains unclear.

Acute-Phase Reaction↗
PubMed1998

Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients.

We have previously shown human lipid-mobilizing factor (LMF) to be homologous with the plasma protein Zn-alpha2-glycoprotein in amino acid sequence, electrophoretic mobility, and immunoreactivity. In this study, both LMF and Zn-alpha2-glycoprotein have been shown to stimulate glycerol release from isolated murine epididymal adipocytes with a comparable dose-response profile. Both LMF and Zn-alpha2-glycoprotein caused a stimulation of adenylate cyclase in murine adipocyte plasma membranes in a GTP-dependent process, with maximum stimulation at 0.1 microM GTP and with saturation at protein concentrations of >5 microg/assay. Administration of LMF to exbreeder male mice over a 89-h period produced a decrease in body weight without a change in food and water intake. Body composition analysis showed a 42% reduction in carcass lipid when compared with controls. Treatment of ob/ob mice with human LMF over a 160-h period also produced a decrease in body weight, with a 19% reduction in carcass fat, without a change in body water or nonfat mass. Serum levels of glycerol and 3-hydroxybutyrate were significantly increased, as was oxygen uptake by interscapular brown adipose tissue, providing evidence of increased lipid mobilization and utilization. Human white adipocytes responded to both LMF and isoprenaline to the same extent, although the maximal response was lower than that for murine white adipocytes. These results suggest that LMF not only has the capacity to induce lipid mobilization and catabolism in mice, but it also has the potential to exert similar effects in cachectic cancer patients.

Adenylyl Cyclases↗