Orlistat and Hydroxycitrate Ameliorate Colon Cancer in Rats: The Impact of Inflammatory Mediators

Abstract Background The impact of the position of the middle colic artery (MCA) bifurcation and the trajectory of the accessory MCA (aMCA) on adequate lymphadenectomy when operating colon cancer have as of yet not been described and/or analysed in the literature. The aim of this study was to determine the MCA bifurcation position to anatomical landmarks and to assess the trajectory of aMCA. Methods The colonic vascular anatomy was manually reconstructed in 3D from high-resolution CT datasets using Osirix MD and 3-matic Medical and analysed. CT datasets were exported as STL files and supplemented with 3D printed models when required. Results Thirty-two datasets were analysed. The MCA bifurcation was left to the superior mesenteric vein (SMV) in 4 (12.1%), in front of SMV in 17 (53.1%) and right to SMV in 11 (34.4%) models. Median distances from the MCA origin to bifurcation were 3.21 (1.18–15.60) cm. A longer MCA bifurcated over or right to SMV, while a shorter bifurcated left to SMV (r = 0.457, p = 0.009). The main MCA direction was towards right in 19 (59.4%) models. When initial directions included left, the bifurcation occurred left to or anterior to SMV in all models. When the initial directions included right, the bifurcation occurred anterior or right to SMV in all models. The aMCA was found in 10 (31.3%) models, following the inferior mesenteric vein (IMV) in 5 near the lower pancreatic border. The IMV confluence was into SMV in 18 (56.3%), splenic vein in 11 (34.4%) and jejunal vein in 3 (9.4%) models. Conclusion Awareness of the wide range of MCA bifurcation positions reported is crucial for the quality of lymphadenectomy performed. The aMCA occurs in 31.3% models and its trajectory is in proximity to the lower pancreatic border in one half of models, indicating that it needs to be considered when operating splenic flexure cancer.

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Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00581-9 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Jiao Wu ◽

Sai-Ching Jim Yeung ◽

Sicheng Liu ◽

Aiham Qdaisat ◽

Dewei Jiang ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Weight Loss ◽

Cancer Patients ◽

Cancer Cell ◽

Cancer Progression ◽

Colorectal Cancer Patient ◽

Nutrition Support ◽

Immunodeficient Mice ◽

The Impact

AbstractWeight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

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The impact of spontaneous tumour perforation on outcome following colon cancer surgery

Colorectal Disease ◽

10.1111/j.1463-1318.2007.01412.x ◽

2008 ◽

Vol 10 (8) ◽

pp. 775-780 ◽

Cited By ~ 46

Author(s):

A. S. Abdelrazeq ◽

N. Scott ◽

C. Thorn ◽

C. S. Verbeke ◽

N. S. Ambrose ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Surgery ◽

Colon Cancer Surgery ◽

The Impact

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The impact of KRAS mutation, microsatellite instability, and tumor laterality on the prognosis of nonmetastatic colon cancer

Surgery ◽

10.1016/j.surg.2021.10.043 ◽

2021 ◽

Author(s):

Catherine G. Tran ◽

Paolo Goffredo ◽

Sarah L. Mott ◽

Alexander Hart ◽

Y. Nancy You ◽

...

Keyword(s):

Colon Cancer ◽

Microsatellite Instability ◽

Kras Mutation ◽

The Impact ◽

Tumor Laterality

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Lymphadenectomy in the Treatment of Colon Cancer: A Survival Nalysis

International Journal of Innovative Research in Medical Science ◽

10.23958/ijirms/vol04-i12/813 ◽

2019 ◽

Vol 4 (12) ◽

Author(s):

Romualdo Silva Corrêa ◽

Luciana Ayres de Oliveira Lima ◽

Isa Maryana Araújo Bezerra de Macedo ◽

Amália Cinhtia Meneses Rêgo ◽

Irami Araújo-Filho

Keyword(s):

Colon Cancer ◽

Lymph Nodes ◽

Medical Records ◽

Survival Rates ◽

Primary Treatment ◽

Term Survival ◽

Kaplan Meier ◽

The Impact ◽

Radiotherapy Treatment

Colon cancer is a curable disease when restricted to the bowel and colectomy, the primary treatment. However, the presence and number of resected lymph nodes influence the therapeutic approach and prognosis of the patient. To evaluate the impact of the number of resected lymph nodes on the overall survival of patients treated for colon cancer at the League of Cancer Hospital - Natal - State of Rio Grande do Norte (RN) - Northeast Brazil. A retrospective observational study of 80 patients with colon cancer from Dr. Luiz Antônio Hospital (Natal-RN / Brazil), considering the period 2007-2014. Data were collected through medical records review. Survival rates were calculated and compared using the non-parametric Kaplan-Meier and Wilcoxon tests, respectively. All patients underwent radical surgical treatment associated or not with chemotherapy and/or radiotherapy treatment. The median survival time for the group of patients who had 12 or more resected lymph nodes was 9.4 years, in contrast to the 3.3 years of those who had less than 12 lymph nodes. Conclusion: It was concluded that a total of 12 or more resected lymph nodes confirmed by histopathology is associated with increased long-term survival in patients with colon cancer undergoing radical colectomy with or without chemotherapy and radiotherapy.

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Oxidative stress-induced inflammation in susceptible airways by anthropogenic aerosol

PLoS ONE ◽

10.1371/journal.pone.0233425 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0233425 ◽

Cited By ~ 1

Author(s):

Zaira Leni ◽

Laure Estelle Cassagnes ◽

Kaspar R. Daellenbach ◽

Imad El Haddad ◽

Athanasia Vlachou ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Mediators ◽

Apical Cell ◽

Ambient Air ◽

Water Soluble ◽

Ambient Air Pollution ◽

Anthropogenic Aerosol ◽

Bronchial Epithelia ◽

Clear Dose Response ◽

The Impact

Ambient air pollution is one of the leading five health risks worldwide. One of the most harmful air pollutants is particulate matter (PM), which has different physical characteristics (particle size and number, surface area and morphology) and a highly complex and variable chemical composition. Our goal was first to comparatively assess the effects of exposure to PM regarding cytotoxicity, release of pro-inflammatory mediators and gene expression in human bronchial epithelia (HBE) reflecting normal and compromised health status. Second, we aimed at evaluating the impact of various PM components from anthropogenic and biogenic sources on the cellular responses. Air-liquid interface (ALI) cultures of fully differentiated HBE derived from normal and cystic fibrosis (CF) donor lungs were exposed at the apical cell surface to water-soluble PM filter extracts for 4 h. The particle dose deposited on cells was 0.9–2.5 and 8.8–25.4 μg per cm2 of cell culture area for low and high PM doses, respectively. Both normal and CF HBE show a clear dose-response relationship with increasing cytotoxicity at higher PM concentrations. The concurrently enhanced release of pro-inflammatory mediators at higher PM exposure levels links cytotoxicity to inflammatory processes. Further, the PM exposure deregulates genes involved in oxidative stress and inflammatory pathways leading to an imbalance of the antioxidant system. Moreover, we identify compromised defense against PM in CF epithelia promoting exacerbation and aggravation of disease. We also demonstrate that the adverse health outcome induced by PM exposure in normal and particularly in susceptible bronchial epithelia is magnified by anthropogenic PM components. Thus, including health-relevant PM components in regulatory guidelines will result in substantial human health benefits and improve protection of the vulnerable population.

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Inflammatory Mediators and Gut Microbial Toxins Drive Colon Tumorigenesis by IL-23 Dependent Mechanism

Cancers ◽

10.3390/cancers13205159 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5159

Author(s):

Janani Panneerselvam ◽

Venkateshwar Madka ◽

Rajani Rai ◽

Katherine T. Morris ◽

Courtney W. Houchen ◽

...

Keyword(s):

Colon Cancer ◽

Dendritic Cells ◽

Tumor Progression ◽

Inflammatory Mediators ◽

Ex Vivo ◽

Colon Tumor ◽

Colonic Tumor ◽

Colon Tumorigenesis ◽

Microbial Toxins

Obesity-associated chronic inflammation predisposes colon cancer risk development. Interleukin-23 (IL-23) is a potential inflammatory mediator linking obesity to chronic colonic inflammation, altered gut microbiome, and colon carcinogenesis. We aimed to elucidate the role of pro-inflammatory eicosanoids and gut bacterial toxins in priming dendritic cells and macrophages for IL-23 secretion to promote colon tumor progression. To investigate the association of IL-23 with obesity and colon tumorigenesis, we utilized TCGA data set and colonic tumors from humans and preclinical models. To understand IL-23 production by inflammatory mediators and gut microbial toxins, we performed several in vitro mechanistic studies to mimic the tumor microenvironment. Colonic tumors were utilized to perform the ex vivo experiments. Our findings showed that IL-23 is elevated in obese individuals, colonic tumors and correlated with reduced disease-free survival. In vitro studies showed that IL-23 treatment increased the colon tumor cell self-renewal, migration, and invasion while disrupting epithelial barrier permeability. Co-culture experiments of educated dendritic cells/macrophages with colon cancer cells significantly increased the tumor aggression by increasing the secretory levels of IL-23, and these observations are further supported by ex vivo rat colonic tumor organotypic experiments. Our results demonstrate gut microbe toxins and eicosanoids facilitate IL-23 production, which plays an important role in obesity-associated colonic tumor progression. This newly identified nexus represents a potential target for the prevention and treatment of obesity-associated colon cancer.

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