Home-Based Exercise Prehabilitation During Preoperative Treatment for Pancreatic Cancer Is Associated With Improvement in Physical Function and Quality of Life.

Purpose: To investigate relationships among physical activity, changes in physical function, and health-related quality of life (HRQOL) among patients with pancreatic adenocarcinoma enrolled in a home-based exercise prehabilitation program. Methods: Patients with resectable pancreatic adenocarcinoma receiving preoperative chemotherapy and/or chemoradiation were enrolled on this prospective, single-arm trial and were advised to perform ≥60 minutes each of moderate-intensity aerobic exercise and strengthening exercise weekly. Activity was measured via self-report and accelerometers, including moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and sedentary activity (SA). Physical function measures at baseline and restaging follow-up included 6-minute walk test (6MWT), 5 times sit-to-stand (5×STS), handgrip strength (HGS), 3-m walk for gait speed (GS), and the PROMIS Physical Function Short Form. HRQOL was measured via the FACT-Hep questionnaire. Results: Fifty participants with mean age 66 years (standard deviation = 8 years) were enrolled. The 6MWT, 5×STS, and GS significantly improved from baseline to restaging follow-up (P=.001, P=.049, and P=.009, respectively). Increases in self-reported aerobic exercise, weekly MVPA, and LPA were associated with improvement in 6MWT (ß=.19, P=.048; ß=.18, P=.03; and ß=.08, P=.03, respectively) and self-reported physical functioning (ß=.02, P=.03; ß=.03, P=.005; and ß=.01, P=.02, respectively). Increased weekly LPA was associated with increased HRQOL (ß=.03, P=.02). Increased SA was associated with decreased HRQOL (ß=-.02,P=.01). Conclusions: Patients with potentially resectable pancreatic cancer exhibit meaningful improvement in physical function with prehabilitation; physical activity was associated with improved physical function and HRQOL. These data highlight the importance of physical activity during treatment for pancreatic cancer.

YY1 inhibits the migration and invasion of pancreatic ductal adenocarcinoma by downregulating the FER/STAT3/MMP2 signaling pathway.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and a high mortality rate. The transcription factor YY1 acts as an inhibitor of many types of tumors. We found that YY1 knockdown promoted the invasion and migration of PANC-1 and BxPC-3 cells; FER knockdown partially restored the promotion of pancreatic cancer caused by YY1 knockdown. In vivo experiments yielded the same results. According to luciferase reporter gene, electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays, YY1 directly binds to the FER promoter region. Moreover, higher level FER expression results in a worse TNM stage and prognosis for patients with PDAC. Furthermore, by downregulating FER, YY1 inhibits the formation of the STAT3-MMP2 complex, thereby suppressing expression of MMP2 and ultimately inhibiting the migration and invasion of pancreatic cancer. Our study demonstrates that the YY1/FER/STAT3/MMP2 axis is associated with the progression of pancreatic cancer and may provide a new therapeutic target for the treatment of pancreatic cancer.

Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells.

BACKGROUND: Costunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers. However, the effect of costunolide on gastric cancer (GC) have remained to be ambiguous. In this study, we investigated the underlying mechanisms of apoptosis induced by costunolide in human gastric adenocarcinoma BGC-823 cells in vitro and in vivo. METHODS: The viability of BGC-823 cells was detected by MTT assay. The apoptosis and mitochondrial membrane potential (ΔΨm) of BGC-823 cells induced by costunolide were analyzed by flow cytometry. The inhibiton of costunolide on human gastric adenocarcinoma was estimated in xenografts in nude mice. Apoptosis related proteins and genes were detected by Western blot and Q-PCR. RESULTS: Costunolide inhibited the viability of BGC-823 cells in a time and concentration dependent manner. Costunolide induced the apoptosis and lowered the ΔΨm of BGC-823 cells significantly. Costunolide increased the expression of Bax, cleaved caspase 9, cleaved caspase 7, cleaved caspase 3 and cleaved poly ADP ribose polymerase (PARP) proteins and decreased the expression of Bcl-2, pro-caspase 9, pro-caspase 7, pro-caspase 3 and PARP proteins. Costunolide upregulated the expression of puma, Bak1 and Bax mRNA and downregulated the expression of Bcl-2 mRNA. In addition, we demonstrated that costunolide inhibited the growth and induced apoptosis of BGC-823 cells xenografted in athymic nude mice. Costunolide increased the expression of cleaved caspase 9, cleaved caspase 3 and Bax proteins and decreased the expression of Bcl-2 protein in xenografted tumor. Costunolide upregulated the expression of puma and Bax mRNA and decreased the expression of Bcl-2 mRNA in xenografted tumor. CONCLUSIONS: Collectively, our results suggested that costunolide induced mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells and could be the candidate drug against GC in clinical practice.

Robot-guided neuromapping during nerve-sparing taTME for low rectal cancer.

PURPOSE: Intraoperative pelvic neuromapping with electrophysiological evaluation of autonomic nerve preservation during robotic total mesorectal excision (TME) for rectal cancer is conventionally performed by the bedside assistant with a hand-guided probe. Our goal was to return autonomy over the neuromonitoring process to the colorectal surgeon operating the robotic console. METHODS: A recently described prototype microfork electrostimulation probe was evaluated intraoperatively during abdominal robotic-assisted transanal TME (taTME) surgery for low rectal cancer in three consecutive male patients. RESULTS: An intraoperative video demonstrates the good control and maneuverability of the prototype probe with electrophysiological confirmation of bilateral pelvic autonomic nerve preservation. CONCLUSIONS: This study presents the first in situ application of a new microfork probe for fully robot-guided neuromapping in three patients undergoing TME surgery for low rectal cancer.

Effects of Omegaven®, EPA, DHA and oxaliplatin on oesophageal adenocarcinoma cell lines growth, cytokine and cell signal biomarkers expression.

BACKGROUND: There is limited evidence assessing the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oesophageal adenocarcinoma, both in vitro and in vivo. We evaluated the effects of the omega-3 PUFA and oxaliplatin on OE33 and OE19 cells. METHOD: The two oesophageal cells were treated with Omegaven® (fish oil emulsion), EPA, DHA and oxaliplatin and incubated for up to 144 h. RESULTS: The following inhibitory effects were observed on OE33 cells: EPA reduced cell growth by 39% (p = 0.001), DHA by 59% (p < 0.000) and Oxaliplatin by 77% (p < 0.000). For OE19 cells, the EPA reduced growth by 1% (p = 0.992), DHA by 26% (p = 0.019) and oxaliplatin by 76% (p < 0.000). For both cells, Omegaven® resulted in reduced cell growth at intermediate concentrations (20-40 µM) and increased cell growth at low (10 µM) and high (50 µM) concentrations. DHA, Omegaven® and oxaliplatin were associated with significant downregulation of VEGF and p53 protein, and upregulation of p21 protein. DHA, Omegaven® and Oxaliplatin also led to significant downregulation of the total ERK1/2 and Akt proteins. CONCLUSION: DHA, Omegaven® and oxaliplatin were associated with downregulation of p53 and VEGF in both cells. Of the PUFAs studied, DHA alone or in combination (Omegaven®) had greater in vitro anti-cancer effects than EPA alone.

Hijiki and sodium arsenite stimulate growth of human colorectal adenocarcinoma cells through ERK1/2 activation.

Hijiki seaweed (Hijikia fusiformes) contains high levels of inorganic arsenic, a known carcinogen. However, scientific reports on carcinogenic risks associated with the consumption of this seaweed are limited. This study investigated the effects of seaweed extracts contaminated with arsenic on two colorectal cancer cell lines. Two seaweed extracts, including Hijiki and red seaweed, induced H508 but not HT29 cell proliferation. Growth induction of H508 cells after treatments with Hijiki and sodium arsenite at concentrations equivalent to arsenic found in Hijiki was observed by both MTT and BrdU assays. Hijiki and sodium arsenite induced epidermal growth factor receptor (EGFR) and ERK1/2 activations. AG1478, an EGFR inhibitor, decreased the activation of EGFR and ERK1/2 induced by Hijiki and sodium arsenite. U0126, an ERK1/2 upstream inhibitor, and atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, but not AG1478 completely inhibited the proliferative effect of Hijiki. Altogether, the results suggest that the presence of arsenic in seaweed may partly contribute to the proliferation of colorectal cancer cells. EGFR-dependent, and -independent ERK1/2 signaling pathways, and mAChR may be involved in the growth stimulation by Hijiki. These results raise concern regarding the potential colorectal cancer risks from regular consumption of Hijiki containing high contents of inorganic arsenic.

The Nutritive Value of Organic and Conventional White Cabbage (Brassica Oleracea L. Var. Capitata) and Anti-Apoptotic Activity in Gastric Adenocarcinoma Cells of Sauerkraut Juice Produced Therof.

White cabbage is one of the most important vegetables grown both in Poland and worldwide. Cabbage contains considerable amounts of bioactive compounds such as glucosinolates, vitamin C, carotenoids, and polyphenols. Some experiments indicate that vegetables from organic production contain more bioactive compounds than those from conventional production, however, only a few studies have been conducted on cruciferous plants. The presented study has proved that organic fresh cabbage, compared to the conventional one, contained significantly less total flavonoids in both years of experiments (3.95 ± 0.21 mg/100 g FW and 3.71 ± 0.33 mg/100 g FW), several flavonoid compounds, total chlorophylls (1.51 ± 0.17 mg/100 g FW and 1.30 ± 0.22 mg/100 g FW) carotenoids, nitrites (0.55 ± 0.04 mg/kg FW and 0.45 ± 0.02 mg/kg FW), and nitrates (0.50 ± 0.13 g/kg FW and 0.47 ± 0.11 g/kg FW). The organic sauerkraut juice, compared to the conventional one, contained significantly more total polyphenols (5.39 ± 0.22 mg/100 g FW and 9.05 ± 1.10 mg/100 g FW) as well as several flavonoids. Only CONV sauerkraut juice produced with the highest N level of fertilization induced a statistical significant increase of the level of necrosis of human stomach gastric adenocarcinoma cell line AGS.

Synergistic inhibition of glioma cell proliferation by Withaferin A and tumor treating fields.

Glioblastoma (GBM) is the most aggressive and lethal form of brain cancer. Standard therapies are non-specific and often of limited effectiveness; thus, efforts are underway to uncover novel, unorthodox therapies against GBM. In previous studies, we investigated Withaferin A, a steroidal lactone from Ayurvedic medicine that inhibits proliferation in cancers including GBM. Another novel approach, tumor treating fields (TTFields), is thought to disrupt mitotic spindle formation and stymie proliferation of actively dividing cells. We hypothesized that combining TTFields with Withaferin A would synergistically inhibit proliferation in glioblastoma. Human glioblastoma cells (GBM2, GBM39, U87-MG) and human breast adenocarcinoma cells (MDA-MB-231) were isolated from primary tumors. The glioma cell lines were genetically engineered to express firefly luciferase. Proliferative potential was assessed either by bioluminescence imaging or cell counting via hemocytometer. TTFields (4 V/cm) significantly inhibited growth of the four cancer cell lines tested (n = 3 experiments per time point, four measurements per sample, p < 0.02 at least; 2-way ANOVA, control vs. treatment). The combination of Withaferin A (10-100 nM) with TTFields significantly inhibited the growth of the glioma cells to a degree beyond that of Withaferin A or TTFields alone. The interaction of the Withaferin A and TTFields on glioma cells was found to be synergistic in nature (p < 0.01, n = 3 experiments). These findings were validated by both bioluminescence and hemocytometric measurements. The combination of Withaferin A with TTFields represents a novel approach to treat GBM in a manner that is likely better than either treatment alone and that is synergistic.

Two-stage Turnbull-Cutait pull-through coloanal anastomosis versus coloanal anastomosis with protective loop ileostomy for low rectal cancer. Protocol for a randomized controlled trial (Turnbull-BCN).

PURPOSE: The aim of this study was to determine whether patients that underwent ultra-low rectal resection for cancer can benefit from the recently reintroduced two-stage Turnbull-Cutait abdominoperineal pull-through procedure. METHODS: Patients with low rectal tumors undergoing radical sphincter-sparing resection are eligible for inclusion in a randomized multicenter study. Whether two-stage Turnbull-Cutait coloanal anastomosis provides significant benefits over hand-sewn coloanal anastomosis and associated lateral ileostomy in terms of postoperative morbidity is the primary endpoint. In addition, the study aims to assess secondary endpoints such as quality of life, fecal incontinence, and locoregional recurrence of the neoplasm. Patients with adenocarcinoma of the lower rectum diagnosed by rigid proctoscopy, with histological confirmation of malignancy, and who are candidates of rectal removal and coloanal anastomosis will be included in a randomized controlled and multicenter trial. Postoperative morbidity is defined as complications that occur within 30 days of the data of the second surgical procedure of the last patient included in the trial. Patients will be followed for a minimum period of 3 years. CONCLUSIONS: The two-stage Turnbull-Cutait coloanal anastomosis may constitute an effective surgical alternative in the current approach to the treatment of low rectal cancer without the need of a temporary loop colostomy, preventing the wide range of complications related to stoma surgery. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov (trial number: NCT01766661). This trial is registered in January 10, 2013.

Effects of zinc supplementation on fatigue and quality of life in patients with colorectal cancer.

OBJECTIVE: To investigate the effects of oral zinc supplementation on fatigue intensity and quality of life of patients during chemotherapy for colorectal cancer. METHODS: A prospective, randomized, double-blinded, placebo-controlled study was conducted with 24 patients on chemotherapy for colorectal adenocarcinoma in a tertiary care public hospital. The study patients received zinc capsules 35mg (Zinc Group, n=10) or placebo (Placebo Group, n=14) orally, twice daily (70mg/day), for 16 weeks, from the immediate postoperative period to the fourth chemotherapy cycle. Approximately 45 days after surgical resection of the tumor, all patients received a chemotherapeutic regimen. Before each of the four cycles of chemotherapy, the Functional Assessment of Chronic Illness Therapy-Fatigue scale was completed. We used a linear mixed model for longitudinal data for statistical analysis. RESULTS: The scores of quality of life and fatigue questionnaires were similar between the groups during the chemotherapy cycles. The Placebo Group presented worsening of quality of life and increased fatigue between the first and fourth cycles of chemotherapy, but there were no changes in the scores of quality of life or fatigue in the Zinc Group. CONCLUSION: Zinc supplementation prevented fatigue and maintained quality of life of patients with colorectal cancer on chemotherapy. OBJETIVO: Investigar os efeitos da suplementação oral de zinco sobre a intensidade da fadiga e a qualidade de vida de pacientes durante a quimioterapia para neoplasia colorretal. MÉTODOS: Estudo prospectivo, randomizado, controlado e duplo-cego conduzido em um hospital universitário público terciário, com 24 pacientes em regime quimioterápico para adenocarcinoma colorretal. Os pacientes receberam cápsulas de zinco 35mg (Grupo Zinco, n=10) ou placebo (Grupo Placebo, n=14) por via oral, duas vezes ao dia (70mg/dia), durante 16 semanas, desde o período pós-operatório imediato até o quarto ciclo de quimioterapia. Todos os pacientes receberam quimioterapia por aproximadamente 45 dias após a ressecção cirúrgica do tumor. A escala Functional Assessment of Chronic Illness Therapy-Fatigue foi preenchida antes de cada um dos quatro ciclos de quimioterapia. Utilizou-se o modelo de regressão linear misto para dados longitudinais para análise estatística. RESULTADOS: Os escores de qualidade de vida e de fadiga foram semelhantes entre os grupos de estudo durante os ciclos de quimioterapia. O Grupo Placebo apresentou piora da qualidade de vida e da fadiga entre o primeiro e o quarto ciclos de quimioterapia, mas não houve mudança nos escores de qualidade de vida e fadiga no Grupo Zinco. CONCLUSÃO: A suplementação com zinco previne a fadiga e preserva a qualidade de vida de pacientes em quimioterapia para neoplasia colorretal.

Assessment of anti-cancerous potential of 6-gingerol (Tongling White Ginger) and its synergy with drugs on human cervical adenocarcinoma cells.

The anti-cancerous activity of 6-gingerol extracted from Tongling White Ginger was investigated. 6-Gingerol inhibited the growth of HeLa cells with IC50 (96.32 µM) and IC80 (133.01 µM) and led to morphological changes, induced the cell cycle arrest in G0/G1-phase and ultimately resulted into apoptosis. Among cell cycle-related genes and proteins, the expression of cyclin (A, D1, E1) reduced, while of CDK-1, p21 and p27 showed slight decrease, except cyclin B1 and E1 (protein). Western blotting reported the induction of apoptosis with an increased Bax/Bcl-2 ratio, release of cytochrome c, cleavage of caspase-3, -8, -9 and PRPP in treated cells. 6-Gingerol activated AMPK, but inhibited PI3K/AKT phosphorylation with reduced P70S6K expression and also suppressed the mTOR phosphorylation. 6-Gingerol with 5-FU and Ptx resulted in 83.2% and 52% inhibition respectively, this synergy have stimulated apoptosis proteins more efficiently as compared to 6-Gingerol alone (10.75%) under in vitro conditions.

Effects of zinc supplementation on fatigue and quality of life in patients with colorectal cancer / Efeitos da suplementação de zinco na fadiga e na qualidade de vida de pacientes com câncer colorretal

ABSTRACT Objective To investigate the effects of oral zinc supplementation on fatigue intensity and quality of life of patients during chemotherapy for colorectal cancer. Methods A prospective, randomized, double-blinded, placebo-controlled study was conducted with 24 patients on chemotherapy for colorectal adenocarcinoma in a tertiary care public hospital. The study patients received zinc capsules 35mg (Zinc Group, n=10) or placebo (Placebo Group, n=14) orally, twice daily (70mg/day), for 16 weeks, from the immediate postoperative period to the fourth chemotherapy cycle. Approximately 45 days after surgical resection of the tumor, all patients received a chemotherapeutic regimen. Before each of the four cycles of chemotherapy, the Functional Assessment of Chronic Illness Therapy-Fatigue scale was completed. We used a linear mixed model for longitudinal data for statistical analysis. Results The scores of quality of life and fatigue questionnaires were similar between the groups during the chemotherapy cycles. The Placebo Group presented worsening of quality of life and increased fatigue between the first and fourth cycles of chemotherapy, but there were no changes in the scores of quality of life or fatigue in the Zinc Group. Conclusion Zinc supplementation prevented fatigue and maintained quality of life of patients with colorectal cancer on chemotherapy.

RESUMO Objetivo Investigar os efeitos da suplementação oral de zinco sobre a intensidade da fadiga e a qualidade de vida de pacientes durante a quimioterapia para neoplasia colorretal. Métodos Estudo prospectivo, randomizado, controlado e duplo-cego conduzido em um hospital universitário público terciário, com 24 pacientes em regime quimioterápico para adenocarcinoma colorretal. Os pacientes receberam cápsulas de zinco 35mg (Grupo Zinco, n=10) ou placebo (Grupo Placebo, n=14) por via oral, duas vezes ao dia (70mg/dia), durante 16 semanas, desde o período pós-operatório imediato até o quarto ciclo de quimioterapia. Todos os pacientes receberam quimioterapia por aproximadamente 45 dias após a ressecção cirúrgica do tumor. A escala Functional Assessment of Chronic Illness Therapy-Fatigue foi preenchida antes de cada um dos quatro ciclos de quimioterapia. Utilizou-se o modelo de regressão linear misto para dados longitudinais para análise estatística. Resultados Os escores de qualidade de vida e de fadiga foram semelhantes entre os grupos de estudo durante os ciclos de quimioterapia. O Grupo Placebo apresentou piora da qualidade de vida e da fadiga entre o primeiro e o quarto ciclos de quimioterapia, mas não houve mudança nos escores de qualidade de vida e fadiga no Grupo Zinco. Conclusão A suplementação com zinco previne a fadiga e preserva a qualidade de vida de pacientes em quimioterapia para neoplasia colorretal.

Effect of prehabilitation in gastro-oesophageal adenocarcinoma: study protocol of a multicentric, randomised, control trial-the PREHAB study.

INTRODUCTION: Perioperative chemotherapy is the gold standard treatment of the resectable gastro-oesophageal adenocarcinoma. However, 70% of patients cannot receive the complete sequence because of a postoperative complication or a decrease in functional and nutritional reserves. Recently, a new concept appeared in digestive surgery: prehabilitation. This interventional process consists of patient preparation, between surgical consultation and surgery, and is based on 3 components: (1) physical management, (2) nutritional care and (3) psychological care. Prehabilitation should decrease postoperative complications and improve nutritional and physical status during the preoperative and postoperative periods. Therefore, it is becoming essential to evaluate the effect of prehabilitation, compared to conventional care, on the percentage of patients reaching the complete oncological treatment. METHODS AND ANALYSIS: The PREHAB trial aimed to evaluate the efficacy of prehabilitation compared to conventional care, in patients with gastro-oesophageal cancer with perioperative chemotherapy. This trial is a prospective, randomised, controlled, open-blind and interventional study in 4 centres. Patients (n=60 per group) will be randomly assigned for management with either prehabilitation or conventional care. The primary outcome is the percentage of patients reaching the complete oncological treatment decided in a multidisciplinary tumour board. The secondary outcomes are the postoperative morbidity, disease-free survival, overall survival, feasibility of the protocol, length of stay, variation of the functional reserve after the preoperative chemotherapy (defined by the VO2peak, ventilatory threshold and 6-min walk test), preoperative and postoperative nutritional status, preoperative anxiety, quality of life, 30-day and 90-day mortality and cumulative dose of cytotoxic treatment received. ETHICS AND DISSEMINATION: The study was approved by an independent medical ethics committee (IRB00008526, CPP Sud-Est VI, Clermont-Ferrand, France) and by the competent French authority (ANSM, Saint Denis, France) and registered on Clinicaltrial.gov. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02780921.

[Synergistic Antitumor Effect of Amorphigenin Combined with Cisplatin in Human Lung Adenocarcinoma A549/DDP Cells].

BACKGROUND: Amorphigenin, a rotenoid compouns, from seeds of Amorpha fruticosa, has been shown to possess anti-proliferation activities in several cancer cells. To explore the antitumor effects of amorphigenin on cisplatin-resistant human lung adenocarcinoma A549/DDP cells and explore the underlying mechanisms. METHODS: CCK-8 assay was used to measure the proliferation of A549/DDP cells; Colony formation assay was used to measure the colony formation of A549/DDP cells; Flow cytometry assay was used to detect the apoptosis rates; Western blot analysis was used to explore the expression of apoptosis-related proteins (caspase-3 protein, PARP protein) and lung resistance protein (LRP). RESULTS: Our results demonstrated that amorphigenin could inhibit the proliferation of A549/DDP cells with a inhibition concentration of 50% cell growth (IC50) at 48 h of (2.19±0.92) µmol/L. Amorphigenin could inhibit the colony formation ability and induce apoptosis of A549/DDP cells; Furthermore, amorphigenin combined with cisplatin showed synergistic proliferation-inhibitory effect and apoptosis-promoting effect in A549/DDP cells; reduced the expression of LRP of A549/DDP cells. CONCLUSIONS: Amorphigenin remarkably inhibits the proliferation and induces apoptosis in A549/DDP cells. Combination of amorphigenin with cisplatin had the synergistic inhibitory effect on A549/DDP cells by downregulating the expression of LRP.
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Sosiho­tang ameliorates cachexia­related symptoms in mice bearing colon 26 adenocarcinoma by reducing systemic inflammation and muscle loss.

Cachexia accompanied by muscle wasting is a key determinant of poor prognosis in cancer patients and cancer­related death. Previous studies have demonstrated that inflammatory cytokines such as interleukin­6 (IL­6), tumor necrosis factor­α (TNF­α), IL­1 and interferon­Î³ (IFN­Î³) secreted from host cells and tumor cells participate in skeletal muscle wasting followed by severe loss of body weight. Therefore, blockade of the inflammatory response is thought to be a logical target for pharmacological and nutritional interventions to preserve skeletal muscle mass under cachectic conditions. Sosiho­tang (SO; Xiaocharihu­tang in Chinese and Sho­saiko­to in Japanese) is an Oriental herbal medicine that has been used to treat chronic hepatic diseases and to control fever. In recent studies, SO inhibited the production of inflammatory cytokines in lipopolysaccharide (LPS)­stimulated macrophages, prevented thrombus formation and suppressed cancer progression. However, the anti­cachectic activity of SO in tumor­bearing mice has not yet been examined. In the present study, we characterized the effect of SO administration on cancer­induced cachexia in CT­26­bearing mice, and elucidated the anti­cachectic mechanisms. Daily oral administration of SO at doses of 50 and 100 mg/kg to CT­26­bearing mice significantly retarded tumor growth and prevented the loss of final body weight, carcass weight, heart weight, gastrocnemius muscle, and epididymal fat, compared with saline­treated control mice. In addition, serum IL­6 levels elevated by cancer were decreased by SO administration. In the J774A.1 macrophage cell line, SO efficiently suppressed LPS­mediated increases in inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO), and procachectic inflammatory cytokine production through inhibition of nuclear factor­κB (NF­κB) and p38 activation. In addition, SO attenuated muscle atrophy caused by cancer cells by affecting myoblast proliferation and differentiation, and C2C12 myotube wasting. Taken together, these results suggest that SO is a safe and useful anti­cachectic therapy for cancer patients with severe weight loss.

Persistent Diarrhea after Celiac Plexus Block in a Pancreatic Cancer Patient: Case Report and Literature Review.

BACKGROUND: Neurolytic celiac plexus block is increasingly used to treat refractory pain associated with abdominal malignancies, especially pancreatic cancer. While self-limiting diarrhea can occur commonly in patients post procedure, a very rare risk of persistent diarrhea exists. OBJECTIVE: We present a case of a 70 year old female with locally advanced pancreatic adenocarcinoma who was hospitalized for persistent severe diarrhea post celiac plexus block and discuss management options for this adverse effect. DESIGN: A review of the current literature within the past 20 years (PubMed and Ovid databases) was conducted to discuss alternatives of management. MEASUREMENTS/RESULTS: Ninety-three entries were found in total including duplicates and only two were included for relevance. Management options that were discussed included anti-motility agents, alpha-adrenergic agonists, and somastatin analog (octreotide). Our patient was initially treated with loperamide, hyoscine, psyllium, and cholestyramine before responding to octreotide. The patient was discharged on long-acting octreotide after her bowel routine stabilized. CONCLUSIONS: Persistent diarrhea is a very rare complication of celiac plexus block and current literature regarding proper management is based largely on anecdotal evidence. For this patient octreotide was an effective agent for the management of this complication.

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma-Past, Present, and Future.

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long-standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5-year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett's esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett's esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett's esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett's carcinogenesis.

Outcomes of systematic nutritional assessment and medical nutrition therapy in pancreatic cancer.

OBJECTIVES: We investigated the nutritional and survival outcomes of medical nutrition therapy by a registered dietitian, along with support from a dedicated nutrition and metabolic support team in pancreatic cancer patients requiring enteral or parenteral nutrition. METHODS: Subjective global assessment (SGA) was used to assess nutritional status in 304 pancreatic cancer patients. Using baseline and last SGA, patients were categorized into 3 groups: improved SGA, deteriorated SGA, and unchanged SGA. Kaplan-Meier and Cox regression were used to calculate survival after controlling for relevant confounders. RESULTS: One-hundred twenty-five (41.1%) patients had their SGA unchanged, 87 (28.6%) patients had "improved SGA," whereas 92 (30.3%) patients had "deteriorated SGA." On univariate survival analysis, the median survival was 7.8, 11.2, and 12.6 months for deteriorated, unchanged, and improved SGA groups, respectively. On multivariate analysis, change in SGA was independently predictive of survival. Patients with deteriorated SGA had 1.5 times (95% confidence interval, 1.1-2.1) greater risk of mortality compared to those with improved SGA. CONCLUSIONS: The majority of pancreatic cancer patients (70%) in our study either maintained or improved their nutritional status during cancer treatment. Improvement in SGA correlated with a significantly decreased risk of mortality independent of sex, previous treatment history, and evidence of biological anticancer activity.

Research on the efficacy of Celastrus Orbiculatus in suppressing TGF-ß1-induced epithelial-mesenchymal transition by inhibiting HSP27 and TNF-α-induced NF-κ B/Snail signaling pathway in human gastric adenocarcinoma.

BACKGROUND: Celastrus orbiculatus has been used as a folk medicine in China for the treatment of many diseases. In the laboratory, the ethyl acetate extract of Celastrus orbiculatus (COE) displays a wide range of anticancer functions. However, the inhibition of the metastasis mechanism of COE in gastric cancer cells has not been investigated so far. METHODS: The present study was undertaken to determine if the anti-metastasis effect of COE was involved in inhibiting of epithelial-mesenchymal transition (EMT) of human gastric adenocarcinoma SGC-7901 cells. In vitro, a well-established experimental EMT model involving transforming growth factor ß1 (TGF-ß1) was applied. Viability, invasion and migration, protein and mRNA expression of tumor cells were analyzed by MTT assay, transwell assay, western blot and real-time PCR, respectively. The molecular targets of COE in SGC-7901 cells were investigated by two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-TOF mass spectrometer. Overexpression of heat shock protein 27 (HSP27) was performed by transfected with the recombinant retroviral expression plasmid. In vivo, the anti-metastasis mechanisms of COE in the peritoneal gastric cancer xenograft model was explored and the effect was tested. RESULTS: The non-cytostatic concentrations of COE effectively inhibited TGF-ß1 induced EMT process in SGC-7901 cells, which is characterized by prevented morphological changes, increased E-cadherin expression and decreased Vimentin, N-cadherin expression. Moreover, COE inhibited invasion and migration induced by TGF-ß1. Using a comparative proteomics approach, four proteins were identified as differently expressed, with HSP27 protein being one of the most significantly down-regulated proteins induced by COE. Moreover, the activation of nuclear factor κB (NF-κB)/Snail signaling pathway induced by tumor necrosis factor-α (TNF-α) was also attenuated under the pretreatment of COE. Interestingly, overexpression of HSP27 significantly decreases the inhibitory effect of COE on EMT and the NF-κB/Snail pathway. Furthermore, COE significantly reduced the number of peritoneal metastatic nodules in the peritoneal gastric cancer xenograft model. CONCLUSIONS: Taken together, these results suggest that COE inhibits the EMT by suppressing the expression of HSP27, correlating with inhibition of NF-κB/Snail signal pathways in SGC-7901 cells. Based on these results, COE may be considered a novel anti-cancer agent for the treatment of metastasis in gastric cancer.

Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma.

BACKGROUND: Yin Yang 1 (YY1) is a transcription factor that regulates diverse biological processes and increasing recognized to have important roles in carcinogenesis. The function and clinical significance of YY1 in gastric adenocarcinoma (GAC) have not been elucidated. METHODS: In this study, the functional role of YY1 in gastric cancer was investigated by MTT proliferation assays, monolayer colony formation, cell cycle analysis, signaling pathway analysis, Western blot analysis and in vivo study through YY1 knockdown or overexpression. Immunohistochemical study with YY1 antibody was performed on tissue microarray consisting of 247 clinical GAC samples. The clinical correlation and prognosis significance were evaluated. RESULTS: YY1 expression was up-regulated in gastric cancer cell lines and primary gastric cancers. Knocking down YY1 by siYY1 inhibited cell growth, inducing G1 phase accumulation and apoptosis. Ectopic YY1 expression enhanced cell proliferation in vitro and in vivo. Knocking down YY1 in gastric cancer cells suppressed proliferation by inhibiting Wnt/ß-catenin pathway, whereas its overexpression exerted oncogenic property by activating Wnt/ß-catenin pathway. In primary GAC samples, YY1 nuclear expression correlated with shorter survival and predicted poor prognosis in early stage GACs. CONCLUSION: Our data demonstrated that YY1 contributes to gastric carcinogenesis in gastric cancer. In early stage GACs YY1 might serve as a poor prognostic marker and possibly as a potential therapeutic target.