Mechanisms and Treatment of Weight Loss in Cancer

Weight loss and the development of cancer cachexia are well known to contribute to the morbidity and mortality of cancer patients. Loss of body mass is most commonly due to an imbalance between energy intake and energy expenditure. The aim of this study was to examine the nature of the negative energy balance in cancer patients and evaluate several new approaches to redress the host-tumour imbalance in cancer cachexia

Evaluating potential biomarkers of cachexia and survival in skeletal muscle of upper gastrointestinal cancer patients

Background  In order to grow the potential therapeutic armamentarium in the cachexia domain of supportive oncology, there is a pressing need to develop suitable biomarkers and potential drug targets. This pilot study evaluated several potential candidate biomarkers in skeletal muscle biopsies from a cohort of upper gastrointestinal cancer (UGIC) patients.  Methods  One hundred seven patients (15 weight-stable healthy controls (HC) and 92 UGIC patients) were recruited. Mean (standard deviation) weight-loss of UGIC patients was 8.1 (9.3\%). Cachexia was defined as weight-loss ≥5\%. Rectus abdominis muscle was obtained at surgery and was analysed by western blotting or quantitative real-time–polymerase chain reaction. Candidate markers were selected according to previous literature and included Akt and phosphorylated Akt (pAkt, n = 52), forkhead box O transcription factors (n = 59), ubiquitin E3 ligases (n = 59, control of muscle anabolism/catabolism), BNIP3 and GABARAPL1 (n = 59, as markers of autophagy), myosin heavy-chain (MyHC, n = 54), dystrophin (n = 39), β-dystroglycan (n = 52), and β-sarcoglycan (n = 52, as markers of structural alteration in a muscle). Patients were followed up for an average of 1255 days (range 581–1955 days) or until death. Patients were grouped accordingly and analysed by (i) all cancer patients vs. HC; (ii) cachectic vs. non-cachectic cancer patients; and (iii) cancer patients surviving ≤1 vs. {\textgreater}1 year post operatively.  Results  Cancer compared with HC patients had reduced mean (standard deviation) total Akt protein [0.49 (0.31) vs. 0.89 (0.17), P = 0.001], increased ratio of phosphorylated to total Akt [1.33 (1.04) vs. 0.32 (0.21), P = 0.002] and increased expression of GABARAPL1 [1.60 (0.76) vs. 1.10 (0.57), P = 0.024]. β-Dystroglycan levels were higher in cachectic compared with non-cachectic cancer patients [1.01 (0.16) vs. 0.87 (0.20), P = 0.007]. Survival was shortened in patients with low compared with high MyHC levels (median 316 vs. 1326 days, P = 0.023) and dystrophin levels (median 341 vs. 660 days, P = 0.008).  Conclusions  The present study has identified intramuscular protein level of β-dystroglycan as a potential biomarker of cancer cachexia. Changes in the structural elements of muscle (MyHC or dystrophin) appear to be survival biomarkers

Dystrophin glycoprotein complex dysfunction:a regulatory link between muscular dystrophy and cancer cachexia

SummaryCachexia contributes to nearly a third of all cancer deaths, yet the mechanisms underlying skeletal muscle wasting in this syndrome remain poorly defined. We report that tumor-induced alterations in the muscular dystrophy-associated dystrophin glycoprotein complex (DGC) represent a key early event in cachexia. Muscles from tumor-bearing mice exhibited membrane abnormalities accompanied by reduced levels of dystrophin and increased glycosylation on DGC proteins. Wasting was accentuated in tumor mdx mice lacking a DGC but spared in dystrophin transgenic mice that blocked induction of muscle E3 ubiquitin ligases. Furthermore, DGC deregulation correlated positively with cachexia in patients with gastrointestinal cancers. Based on these results, we propose that, similar to muscular dystrophy, DGC dysfunction plays a critical role in cancer-induced wasting

The impact of helmets on motorcycle head trauma at a tertiary hospital in Jamaica

<p>Abstract</p> <p>Background</p> <p>Although the Jamaica road traffic act mandates motorcycle riders to wear approved helmets, opponents suggest that the local road conditions obviate any benefits from helmet use that have been proven in Developed countries. They suggest that the narrow, winding, poorly surfaced, congested local highways do not allow motorcyclists to sustain high velocity travel. The accidents then tend to occur at lower speeds and are accompanied by less severe injuries. This study was carried out to determine the impact of helmet use on traumatic brain injuries from motorcycle collisions in patients admitted to a tertiary referral hospital in Jamaica.</p> <p>Methods</p> <p>A prospectively collected trauma registry maintained by the Department of Surgery at the University Hospital of the West Indies in Jamaica was accessed to identify all motorcycle collision victims from January 2000 to January 2007. The therapeutic outcomes of traumatic brain injuries were compared between helmeted and un-helmeted riders. The data was analyzed using SPSS Version 12.</p> <p>Results</p> <p>Of 293 motorcycle collision victims, 143 sustained brain injuries. There were 9 females (6.3%) with an average age of 23 +/- 7.3 years and 134 males (93.7%) at an average age of 33.4 +/- 11.2 years (mean +/- SD). Only 49 (34.3%) patients wore a helmet at the time of a collision. Helmet use at the time of a collision significantly reduced the severity of head injuries (28.6% vs 46.8%, P = 0.028) and the likelihood of sustaining intra-cranial lesions (26.5% vs 44.7%, P = 0.03) from head injuries.</p> <p>Conclusion</p> <p>Wearing a helmet at the time of a motorcycle collision reduces the severity of head injuries. However, the prevalence of helmet use at the time of a collision is unacceptably low.</p

“How Long Have I Got?”—A Prospective Cohort Study Comparing Validated Prognostic Factors for Use in Patients with Advanced Cancer

© AlphaMed Press 2019 Background: The optimal prognostic factors in patients with advanced cancer are not known, as a comparison of these is lacking. The aim of the present study was to determine the optimal prognostic factors by comparing validated factors. Materials and Methods: A multicenter, prospective observational cohort study recruited patients over 18 years with advanced cancer. The following were assessed: clinician-predicted survival (CPS), Eastern Cooperative Oncology Group performance status (ECOG-PS), patient reported outcome measures (anorexia, cognitive impairment, dyspnea, global health), metastatic disease, weight loss, modified Glasgow Prognostic Score (mGPS) based on C-reactive protein and albumin, lactate dehydrogenase (LDH), and white (WCC), neutrophil (NC), and lymphocyte cell counts. Survival at 1 and 3 months was assessed using area under the receiver operating curve and logistic regression analysis. Results: Data were available on 478 patients, and the median survival was 4.27 (1.86–7.03) months. On univariate analysis, the following factors predicted death at 1 and 3 months: CPS, ECOG-PS, mGPS, WCC, NC (all

The Human Urinary Proteome Fingerprint Database UPdb

Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177The use of human urine as a diagnostic tool has many advantages, such as ease of sample acquisition and noninvasiveness. However, the discovery of novel biomarkers, as well as biomarker patterns, in urine is hindered mainly by a lack of comparable datasets. To fill this gap, we assembled a new urinary fingerprint database. Here, we report the establishment of a human urinary proteomic fingerprint database using urine from 200 individuals analysed by SELDI-TOF (surface enhanced laser desorption ionisation-time of flight) mass spectrometry (MS) on several chip surfaces (SEND, HP50, NP20, Q10, CM10, and IMAC30). The database currently lists 2490 unique peaks/ion species from 1172 nonredundant SELDI analyses in the mass range of 1500 to 150000. All unprocessed mass spectrometric scans are available as “.xml” data files. Additionally, 1384 peaks were included from external studies using CE (capillary electrophoresis)-MS, MALDI (matrix assisted laser desorption/ionisation), and CE-MALDI hybrids. We propose to use this platform as a global resource to share and exchange primary data derived from MS analyses in urinary research.https://doi.org/10.1155/2013/7602082013pubpub76020