Serum antibody response to Moraxella catarrhalis proteins OMP CD, OppA, Msp22, Hag, and PilA2 after nasopharyngeal colonization and acute otitis media in children

PubMed Central

Ren, Dabin; Almudevar, Anthony L.; Murphy, Timothy F.; Lafontaine, Eric R.; Campagnari, Anthony A.; Luke-Marshall, Nicole; Casey, Janet R.; Pichichero, Michael E.

2015-01-01

Background There is no licensed vaccine for Moraxella catarrhalis (Mcat), which is a prominent bacterium causing acute otitis media (AOM) in children and lower respiratory tract infections in adults. Nasopharyngeal (NP) colonization caused by respiratory bacteria results in natural immunization of the host. To identify Mcat antigens as vaccine candidates, we evaluated the development of naturally induced antibodies to 5 Mcat surface proteins in children 6–30 months of age during Mcat NP colonization and AOM. Methods Human serum IgG against the recombinant Mcat proteins, outer membrane protein (OMP) CD, oligopeptide permease (Opp)A, hemagglutinin (Hag), Moraxella surface protein (Msp)22, and PilA clade 2 (PilA2) was quantitated by using an ELISA assay. Results There were 223 Mcat NP colonization episodes documented in 111 (60%) of 184 children in the study. Thirty five Mcat AOM episodes occurred in 30 (16%) of 184 children. All 5 Mcat candidate vaccine antigens evaluated stimulated a significant rise in serum IgG levles over time from 6 to 36 months of age (P < 0.001), with a rank order as follows: Msp22 = OppA > OMP CD = Hag = PilA2. Children with no detectable Mcat NP colonization showed a higher serum IgG level against OppA, Hag, and Msp22 compared to those with Mcat NP colonization (P < 0.05). Individual data showed that some children responded to AOM with an antibody increase to one or more of the studied Mcat proteins but some children failed to respond. Conclusions Serum antibody to Mcat candidate vaccine proteins OMP CD, OppA, Msp22, Hag, and PilA2 increased with age in naturally immunized children age 6–30 months following Mcat NP colonization and AOM. High antibody levels against OppA, Msp22, and Hag correlated with reduced carriage. The results support further investigation of these vaccine candidates in protecting against Mcat colonization and infection. PMID:26392013

Human Antibodies to PhtD, PcpA, and Ply Reduce Adherence to Human Lung Epithelial Cells and Murine Nasopharyngeal Colonization by Streptococcus pneumoniae

PubMed Central

Kaur, Ravinder; Surendran, Naveen; Ochs, Martina

2014-01-01

Streptococcus pneumoniae adherence to human epithelial cells (HECs) is the first step in pathogenesis leading to infections. We sought to determine the role of human antibodies against S. pneumoniae protein vaccine candidates PhtD, PcpA, and Ply in preventing adherence to lung HECs in vitro and mouse nasopharyngeal (NP) colonization in vivo. Human anti-PhtD, -PcpA, and -Ply antibodies were purified and Fab fragments generated. Fabs were used to test inhibition of adherence of TIGR4 and nonencapsulated strain RX1 to A549 lung HECs. The roles of individual proteins in adherence were tested using isogenic mutants of strain TIGR4. Anti-PhtD, -PcpA, and -Ply human antibodies were assessed for their ability to inhibit NP colonization in vivo by passive transfer of human antibody in a murine model. Human antibodies generated against PhtD and PcpA caused a decrease in adherence to A549 cells (P < 0.05). Anti-PhtD but not anti-PcpA antibodies showed a protective role against mouse NP colonization. To our surprise, anti-Ply antibodies also caused a significant (P < 0.05) reduction in S. pneumoniae colonization. Our results support the potential of PhtD, PcpA, and Ply protein vaccine candidates as alternatives to conjugate vaccines to prevent non-serotype-specific S. pneumoniae colonization and invasive infection. PMID:25245804

Human antibodies to PhtD, PcpA, and Ply reduce adherence to human lung epithelial cells and murine nasopharyngeal colonization by Streptococcus pneumoniae.

PubMed

Kaur, Ravinder; Surendran, Naveen; Ochs, Martina; Pichichero, Michael E

2014-12-01

Streptococcus pneumoniae adherence to human epithelial cells (HECs) is the first step in pathogenesis leading to infections. We sought to determine the role of human antibodies against S. pneumoniae protein vaccine candidates PhtD, PcpA, and Ply in preventing adherence to lung HECs in vitro and mouse nasopharyngeal (NP) colonization in vivo. Human anti-PhtD, -PcpA, and -Ply antibodies were purified and Fab fragments generated. Fabs were used to test inhibition of adherence of TIGR4 and nonencapsulated strain RX1 to A549 lung HECs. The roles of individual proteins in adherence were tested using isogenic mutants of strain TIGR4. Anti-PhtD, -PcpA, and -Ply human antibodies were assessed for their ability to inhibit NP colonization in vivo by passive transfer of human antibody in a murine model. Human antibodies generated against PhtD and PcpA caused a decrease in adherence to A549 cells (P < 0.05). Anti-PhtD but not anti-PcpA antibodies showed a protective role against mouse NP colonization. To our surprise, anti-Ply antibodies also caused a significant (P < 0.05) reduction in S. pneumoniae colonization. Our results support the potential of PhtD, PcpA, and Ply protein vaccine candidates as alternatives to conjugate vaccines to prevent non-serotype-specific S. pneumoniae colonization and invasive infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Deoxyelephantopin from Elephantopus scaber L. induces cell-cycle arrest and apoptosis in the human nasopharyngeal cancer CNE cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Miaoxian; Chung, Hau Yin, E-mail: anthonychung@cuhk.edu.hk; Food and Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR

2011-07-29

Highlights: {yields} Deoxyelephantopin (ESD) inhibited cell proliferation in the human nasopharyngeal cancer CNE cells. {yields} ESD induced cell cycle arrest in S and G2/M phases via modulation of cell cycle regulatory proteins. {yields} ESD triggered apoptosis by dysfunction of mitochondria and induction of both intrinsic and extrinsic apoptotic signaling pathways. {yields} ESD also triggered Akt, ERK, and JNK signaling pathways. -- Abstract: Deoxyelephantopin (ESD), a naturally occurring sesquiterpene lactone present in the Chinese medicinal herb, Elephantopus scaber L. exerted anticancer effects on various cultured cancer cells. However, the cellular mechanisms by which it controls the development of the cancer cellsmore » are unavailable, particularly the human nasopharyngeal cancer CNE cells. In this study, we found that ESD inhibited the CNE cell proliferation. Cell cycle arrest in S and G2/M phases was also found. Western blotting analysis showed that modulation of cell cycle regulatory proteins was responsible for the ESD-induced cell cycle arrest. Besides, ESD also triggered apoptosis in CNE cells. Dysfunction in mitochondria was found to be associated with the ESD-induced apoptosis as evidenced by the loss of mitochondrial membrane potential ({Delta}{Psi}m), the translocation of cytochrome c, and the regulation of Bcl-2 family proteins. Despite the Western blotting analysis showed that both intrinsic and extrinsic apoptotic pathways (cleavage of caspases-3, -7, -8, -9, and -10) were triggered in the ESD-induced apoptosis, additional analysis also showed that the induction of apoptosis could be achieved by the caspase-independent manner. Besides, Akt, ERK and JNK pathways were found to involve in ESD-induced cell death. Overall, our findings provided the first evidence that ESD induced cell cycle arrest, and apoptosis in CNE cells. ESD could be a potential chemotherapeutic agent in the treatment of nasopharyngeal cancer (NPC).« less

Diabetes-induced mechanophysiological changes in the small intestine and colon

PubMed Central

Zhao, Mirabella; Liao, Donghua; Zhao, Jingbo

2017-01-01

The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients. PMID:28694926

Risk Factors for Pneumococcal Colonization of the Nasopharynx in Alaska Native Adults and Children.

PubMed

Reisman, Jonathan; Rudolph, Karen; Bruden, Dana; Hurlburt, Debby; Bruce, Michael G; Hennessy, Thomas

2014-06-01

Alaska Native children have high invasive pneumococcal disease (IPD) rates, and lack of in-home running water has been shown to have a significant association with infection. Pneumococcal conjugate vaccines reduced IPD; however, this population saw substantial replacement disease and colonization with nonvaccine serotypes. We evaluated risk factors for nasopharyngeal pneumococcal colonization in Alaska Native adults and children. We conducted annual surveys from 2008 through 2011 of residents of all ages in 8 rural Alaskan villages. Interviews were conducted, medical charts were reviewed, and nasopharyngeal swabs were cultured for Streptococcus pneumoniae. Multivariate logistic regression models were developed for 3 age groups (under 10 years, 10-17 years, and 18 years and older) to determine risk factors for colonization. We obtained 12 535 nasopharyngeal swabs from 4980 participants. Our population lived in severely crowded conditions, and 48% of households lacked in-home running water. In children <10 years, colonization was associated with lack of in-home running water, household crowding, and more children in the home. Pneumococcal vaccination status was not associated with colonization. In older children and adults, increased number of persons in the household was associated with pneumococcal colonization. Higher colonization prevalence may partially explain increased IPD rates seen in those lacking in-home water services. Improving availability of sanitation services and reducing household crowding may reduce the burden of IPD in this population. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Epidemiological study of nasopharyngeal carriers of Streptococcus pneumoniae in children in Murcia region].

PubMed

Alfayate-Miguélez, Santiago; Ruiz-Gómez, Joaquín; Fenoll-Comes, Asunción; Sanchez-Solis-de Querol, Manuel; Iofrío-de Arce, Antonio; Casquet-Barceló, Angela; Sanz-Mateo, Gonzalo; Espejo-García, Pilar; Lorente-García, Sebastián; Sánchez-Andrada, Rosa M; Vigueras-Abellán, Juan José

2014-01-01

Streptococcus pneumoniae is a human pathogen that requires prior nasopharyngeal colonization to cause disease. An epidemiological study was conducted on nasopharyngeal carriers of pneumococci in healthy children in Murcia after the introduction of the VCN7, and immediately before the marketing of new vaccines, with the aim of determining the influence of vaccination in our geographic area, and other factors in relation to the state of being a carrier, and the different circulating serotypes. A multicentre study was conducted in in 60 primary care health centres in summer 2009 and winter of 2010. A nasopharyngeal swab was collected, and an epidemiological study was carried out on 1562 children aged 1 and 4 years. Of the 1562 nasopharyngeal samples, pneumococci were found in 489 of them, with 343 of them able to be serotyped (70.2%). The prevalence of carriers was 31.3%. Of the patients included, 61.7% (964/1562) had received at least one dose of VCN7. Only 12.8% of the identified serotypes were vaccine serotypes. The independent protective factors against colonization were; Summer time in all age groups, previous vaccination in all the children (OR: 0.75; 95%CI: 0.56-0.93]; P=.01, and in 1-year-olds (OR: 0.6; 95%CI: 0.42-0.84; P=.002), and had taken antibiotics in the last month in the total cohort [OR: 0.69; 95%CI: 0.50-0.96). On the other hand, attendance at school or day-care centre (OR: 1.85; 95%CI: 1.27-2.18; P=.001), number of siblings (OR: 1.3; 95%CI: 1.01-1.91), and passive tobacco smoke exposure (OR: 1.33; 95%CI: 1.02-1.73), were colonization risk factors. The serotypes 6A, 19A, 23B, 15A/B, 11A, 14, 23A/F, 3 y 19F were the most prevalent. A low proportion of SV was found, with 14, 23F and 19F are persisting. A high prevalence of serotypes 6A and 19A was found. Summer time, vaccination, and the prior administration of antibiotics proved to be protective against colonization, whereas schooling, smoking, and siblings contributed to it. Copyright © 2012

Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research.

PubMed

Tetteh, Paul W; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; Morsink, Folkert; Farin, Henner; van Es, Johan H; Offerhaus, G Johan A; Clevers, Hans

2016-10-18

Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic anhydrase I (Car1) is a gene expressed uniquely in colonic epithelial cells. We generated a colon-specific inducible Car1 CreER knock-in (KI) mouse with broad Cre activity in epithelial cells of the proximal colon and cecum. Deletion of the tumor suppressor gene Apc using the Car1 CreER KI caused tumor formation in the cecum but did not yield adenomas in the proximal colon. Mutation of both Apc and Kras yielded microadenomas in both the cecum and the proximal colon, which progressed to macroadenomas with significant morbidity. Aggressive carcinomas with some invasion into lymph nodes developed upon combined induction of oncogenic mutations of Apc, Kras, p53, and Smad4 Importantly, no adenomas were observed in the small intestine. Additionally, we observed tumors from differentiated Car1-expressing cells with Apc/Kras mutations, suggesting that a top-down model of intestinal tumorigenesis can occur with multiple mutations. Our results establish the Car1 CreER KI as a valuable mouse model to study colon-specific tumorigenesis and metastasis as well as cancer-cell-of-origin questions.

Salmonella induces prominent gene expression in the rat colon

PubMed Central

Rodenburg, Wendy; Keijer, Jaap; Kramer, Evelien; Roosing, Susanne; Vink, Carolien; Katan, Martijn B; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg MJ

2007-01-01

Background Salmonella enteritidis is suggested to translocate in the small intestine. In vivo it induces gene expression changes in the ileal mucosa and Peyer's patches. Stimulation of Salmonella translocation by dietary prebiotics fermented in colon suggests involvement of the colon as well. However, effects of Salmonella on colonic gene expression in vivo are largely unknown. We aimed to characterize time dependent Salmonella-induced changes of colonic mucosal gene expression in rats using whole genome microarrays. For this, rats were orally infected with Salmonella enteritidis to mimic a foodborne infection and colonic gene expression was determined at days 1, 3 and 6 post-infection (n = 8 rats per time-point). As fructo-oligosaccharides (FOS) affect colonic physiology, we analyzed colonic mucosal gene expression of FOS-fed versus cellulose-fed rats infected with Salmonella in a separate experiment. Colonic mucosal samples were isolated at day 2 post-infection. Results Salmonella affected transport (e.g. Chloride channel calcium activated 6, H+/K+ transporting Atp-ase), antimicrobial defense (e.g. Lipopolysaccharide binding protein, Defensin 5 and phospholipase A2), inflammation (e.g. calprotectin), oxidative stress related genes (e.g. Dual oxidase 2 and Glutathione peroxidase 2) and Proteolysis (e.g. Ubiquitin D and Proteosome subunit beta type 9). Furthermore, Salmonella translocation increased serum IFNγ and many interferon-related genes in colonic mucosa. The gene most strongly induced by Salmonella infection was Pancreatitis Associated Protein (Pap), showing >100-fold induction at day 6 after oral infection. Results were confirmed by Q-PCR in individual rats. Stimulation of Salmonella translocation by dietary FOS was accompanied by enhancement of the Salmonella-induced mucosal processes, not by induction of other processes. Conclusion We conclude that the colon is a target tissue for Salmonella, considering the abundant changes in mucosal gene expression

Salmonella induces prominent gene expression in the rat colon.

PubMed

Rodenburg, Wendy; Keijer, Jaap; Kramer, Evelien; Roosing, Susanne; Vink, Carolien; Katan, Martijn B; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M J

2007-09-12

Salmonella enteritidis is suggested to translocate in the small intestine. In vivo it induces gene expression changes in the ileal mucosa and Peyer's patches. Stimulation of Salmonella translocation by dietary prebiotics fermented in colon suggests involvement of the colon as well. However, effects of Salmonella on colonic gene expression in vivo are largely unknown. We aimed to characterize time dependent Salmonella-induced changes of colonic mucosal gene expression in rats using whole genome microarrays. For this, rats were orally infected with Salmonella enteritidis to mimic a foodborne infection and colonic gene expression was determined at days 1, 3 and 6 post-infection (n = 8 rats per time-point). As fructo-oligosaccharides (FOS) affect colonic physiology, we analyzed colonic mucosal gene expression of FOS-fed versus cellulose-fed rats infected with Salmonella in a separate experiment. Colonic mucosal samples were isolated at day 2 post-infection. Salmonella affected transport (e.g. Chloride channel calcium activated 6, H+/K+ transporting Atp-ase), antimicrobial defense (e.g. Lipopolysaccharide binding protein, Defensin 5 and phospholipase A2), inflammation (e.g. calprotectin), oxidative stress related genes (e.g. Dual oxidase 2 and Glutathione peroxidase 2) and Proteolysis (e.g. Ubiquitin D and Proteosome subunit beta type 9). Furthermore, Salmonella translocation increased serum IFN gamma and many interferon-related genes in colonic mucosa. The gene most strongly induced by Salmonella infection was Pancreatitis Associated Protein (Pap), showing >100-fold induction at day 6 after oral infection. Results were confirmed by Q-PCR in individual rats. Stimulation of Salmonella translocation by dietary FOS was accompanied by enhancement of the Salmonella-induced mucosal processes, not by induction of other processes. We conclude that the colon is a target tissue for Salmonella, considering the abundant changes in mucosal gene expression.

Berberine Induces Caspase-Independent Cell Death in Colon Tumor Cells through Activation of Apoptosis-Inducing Factor

PubMed Central

Wang, Lihong; Liu, Liping; Shi, Yan; Cao, Hanwei; Chaturvedi, Rupesh; Calcutt, M. Wade; Hu, Tianhui; Ren, Xiubao; Wilson, Keith T.; Polk, D. Brent; Yan, Fang

2012-01-01

Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the mouse immorto-Min colonic epithelial (IMCE) cells carrying the Apc min mutation, and of normal colon epithelial cells, namely young adult mouse colonic epithelium (YAMC) cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells. In contrast, YAMC cells were not sensitive to berberine-induced cell death. Berberine did not stimulate caspase activation, and PARP cleavage and berberine-induced cell death were not affected by a caspase inhibitor in IMCE cells. Rather, berberine stimulated a caspase-independent cell death mediator, apoptosis-inducing factor (AIF) release from mitochondria and nuclear translocation in a ROS production-dependent manner. Amelioration of berberine-stimulated ROS production or suppression of AIF expression blocked berberine-induced cell death and LDH release in IMCE cells. Furthermore, two targets of ROS production in cells, cathepsin B release from lysosomes and PARP activation were induced by berberine. Blockage of either of these pathways decreased berberine-induced AIF activation and cell death in IMCE cells. Thus, berberine-stimulated ROS production leads to cathepsin B release and PARP activation-dependent AIF activation, resulting in caspase-independent cell death in colon tumor cells. Notably, normal colon epithelial cells are less susceptible to berberine-induced cell death, which suggests the specific inhibitory effects of berberine on colon tumor cell growth. PMID:22574158

Identifying novel genes and chemicals related to nasopharyngeal cancer in a heterogeneous network.

PubMed

Li, Zhandong; An, Lifeng; Li, Hao; Wang, ShaoPeng; Zhou, You; Yuan, Fei; Li, Lin

2016-05-05

Nasopharyngeal cancer or nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The factors that induce nasopharyngeal cancer are still not clear. Additional information about the chemicals or genes related to nasopharyngeal cancer will promote a better understanding of the pathogenesis of this cancer and the factors that induce it. Thus, a computational method NPC-RGCP was proposed in this study to identify the possible relevant chemicals and genes based on the presently known chemicals and genes related to nasopharyngeal cancer. To extensively utilize the functional associations between proteins and chemicals, a heterogeneous network was constructed based on interactions of proteins and chemicals. The NPC-RGCP included two stages: the searching stage and the screening stage. The former stage is for finding new possible genes and chemicals in the heterogeneous network, while the latter stage is for screening and removing false discoveries and selecting the core genes and chemicals. As a result, five putative genes, CXCR3, IRF1, CDK1, GSTP1, and CDH2, and seven putative chemicals, iron, propionic acid, dimethyl sulfoxide, isopropanol, erythrose 4-phosphate, β-D-Fructose 6-phosphate, and flavin adenine dinucleotide, were identified by NPC-RGCP. Extensive analyses provided confirmation that the putative genes and chemicals have significant associations with nasopharyngeal cancer.

Identifying novel genes and chemicals related to nasopharyngeal cancer in a heterogeneous network

PubMed Central

Li, Zhandong; An, Lifeng; Li, Hao; Wang, ShaoPeng; Zhou, You; Yuan, Fei; Li, Lin

2016-01-01

Nasopharyngeal cancer or nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The factors that induce nasopharyngeal cancer are still not clear. Additional information about the chemicals or genes related to nasopharyngeal cancer will promote a better understanding of the pathogenesis of this cancer and the factors that induce it. Thus, a computational method NPC-RGCP was proposed in this study to identify the possible relevant chemicals and genes based on the presently known chemicals and genes related to nasopharyngeal cancer. To extensively utilize the functional associations between proteins and chemicals, a heterogeneous network was constructed based on interactions of proteins and chemicals. The NPC-RGCP included two stages: the searching stage and the screening stage. The former stage is for finding new possible genes and chemicals in the heterogeneous network, while the latter stage is for screening and removing false discoveries and selecting the core genes and chemicals. As a result, five putative genes, CXCR3, IRF1, CDK1, GSTP1, and CDH2, and seven putative chemicals, iron, propionic acid, dimethyl sulfoxide, isopropanol, erythrose 4-phosphate, β-D-Fructose 6-phosphate, and flavin adenine dinucleotide, were identified by NPC-RGCP. Extensive analyses provided confirmation that the putative genes and chemicals have significant associations with nasopharyngeal cancer. PMID:27149165

In vivo adaptation and persistence of Neisseria meningitidis within the nasopharyngeal mucosa.

PubMed

Johswich, Kay O; McCaw, Shannon E; Islam, Epshita; Sintsova, Anna; Gu, Angel; Shively, John E; Gray-Owen, Scott D

2013-01-01

Neisseria meningitidis (Nme) asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa.

In Vivo Adaptation and Persistence of Neisseria meningitidis within the Nasopharyngeal Mucosa

PubMed Central

Johswich, Kay O.; McCaw, Shannon E.; Islam, Epshita; Sintsova, Anna; Gu, Angel; Shively, John E.; Gray-Owen, Scott D.

2013-01-01

Neisseria meningitidis (Nme) asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa. PMID:23935487

Antibody response to Streptococcus pneumoniae proteins PhtD, LytB, PcpA, PhtE and Ply after nasopharyngeal colonization and acute otitis media in children.

PubMed

Pichichero, Michael E; Kaur, Ravinder; Casey, Janet R; Xu, Qingfu; Almudevar, Anthony; Ochs, Martina

2012-06-01

We prospectively compared serum antibody levels of 5 Streptococcus pneumoniae (Spn) proteins: PcpA PhtD, PhtE Ply and LytB associated with nasopharyngeal (NP) colonization and acute otitis media (AOM) infection in a cohort of 6-30 mo old children. Antigen-specific antibody titers were determined by ELISA. A total of 731 visits among 168 children were studied. There were 301 Spn NP colonization episodes documented in 109 (65%) children and 42 Spn AOM episodes in 34 (20%) children. IgG antibody titers to the 5 proteins were significantly different among children over time (p < 0.001), with a rank order as follows: PcpA > PhtE = PhtD > Ply > LytB Characterization of IgG and IgM acute and convalescent serum antibody levels of Spn AOM infection showed the kinetics of the response differed among children, with the same rank order of antibody levels over time. Individual data showed that some children responded to AOM with an antibody increase to one or more of these Spn proteins but some children failed to respond. We conclude that antibody levels to Spn proteins PcpA PhtD, PhtE, Ply and LytB, all rise over time in children age 6 to 30 mo following natural exposure to Spn after NP colonization and AOM; however, there were significant differences in quantity of antibody elicited among these potential vaccine antigens.

Hydroxy-α sanshool induces colonic motor activity in rat proximal colon: a possible involvement of KCNK9

PubMed Central

Kubota, Kunitsugu; Ohtake, Nobuhiro; Ohbuchi, Katsuya; Mase, Akihito; Imamura, Sachiko; Sudo, Yuka; Miyano, Kanako; Yamamoto, Masahiro; Kono, Toru

2015-01-01

Various colonic motor activities are thought to mediate propulsion and mixing/absorption of colonic content. The Japanese traditional medicine daikenchuto (TU-100), which is widely used for postoperative ileus in Japan, accelerates colonic emptying in healthy humans. Hydroxy-α sanshool (HAS), a readily absorbable active ingredient of TU-100 and a KCNK3/KCNK9/KCNK18 blocker as well as TRPV1/TRPA1 agonist, has been investigated for its effects on colonic motility. Motility was evaluated by intraluminal pressure and video imaging of rat proximal colons in an organ bath. Distribution of KCNKs was investigated by RT-PCR, in situ hybridization, and immunohistochemistry. Current and membrane potential were evaluated with use of recombinant KCNK3- or KCNK9-expressing Xenopus oocytes and Chinese hamster ovary cells. Defecation frequency in rats was measured. HAS dose dependently induced strong propulsive “squeezing” motility, presumably as long-distance contraction (LDC). TRPV1/TRPA1 agonists induced different motility patterns. The effect of HAS was unaltered by TRPV1/TRPA1 antagonists and desensitization. Lidocaine (a nonselective KCNK blocker) and hydroxy-β sanshool (a geometrical isomer of HAS and KCNK3 blocker) also induced colonic motility as a rhythmic propagating ripple (RPR) and a LDC-like motion, respectively. HAS-induced “LDC,” but not lidocaine-induced “RPR,” was abrogated by a neuroleptic agent tetrodotoxin. KCNK3 and KCNK9 were located mainly in longitudinal smooth muscle cells and in neural cells in the myenteric plexus, respectively. Administration of HAS or TU-100 increased defecation frequency in normal and laparotomy rats. HAS may evoke strong LDC possibly via blockage of the neural KCNK9 channel in the colonic myenteric plexus. PMID:25634809

Adipokine regulation of colon cancer: adiponectin attenuates interleukin-6-induced colon carcinoma cell proliferation via STAT-3

PubMed Central

Fenton, Jenifer I; Birmingham, Janette M

2010-01-01

Obesity results in increased circulating levels of specific adipokines which are associated with colon cancer risk. The disease state is associated with increased leptin, insulin, IGF-1, and IL-6. Conversely, adiponectin levels are decreased in obese individuals. Previously, we demonstrated adipokine-enhanced cell proliferation in preneoplastic, but not normal, colon epithelial cells, demonstrating a differential effect of adipokines on colon cancer progression in vitro. Using a model of late stage carcinoma cancer cell, namely murine MC-38 colon carcinoma cells, we compared the effect of obesity-associated adipokines (leptin, insulin and IGF-1 and IL-6) on MC-38 cell proliferation and determined whether adiponectin (full length or globular) could modulate adipokine-induced cell proliferation. We show that insulin and IL-6, but not leptin and IGF-1, induce proliferation in MC-38 cells. Adiponectin treatment of MC-38 cells did not inhibit insulin-induced cell proliferation but did inhibit IL-6-induced cell proliferation by decreasing STAT-3 phosphorylation and activation. Nitric oxide (NO) production was increased in MC-38 cells treated with IL-6; co-treatment with adiponectin blocked IL-6 induced iNOS and subsequent NO production. These data are compared to previously reported findings from our laboratory using the YAMC (model normal colon epithelial cells) and IMCE (model preneoplastic) cells. The cell lines are utilized to construct a model summarizing the hormonal consequences of obesity and the impact on the differential regulation of colon epithelial cells along the continuum to carcinoma. These data, taken together, highlight mechanisms involved in obesity-associated cancers and may lead to potential targeted therapies. PMID:20564347

XRCC3 polymorphisms are associated with the risk of developing radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with intensity modulation radiated therapy.

PubMed

Zou, Yan; Song, Tao; Yu, Wei; Zhao, Ruping; Wang, Yong; Xie, Ruifei; Chen, Tian; Wu, Bo; Wu, Shixiu

2014-03-01

The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.

Phenotypic alterations induced by the Hong Kong-prevalent Epstein-Barr virus-encoded LMP1 variant (2117-LMP1) in nasopharyngeal epithelial cells.

PubMed

Lo, Angela Kwok Fung; Huang, Dolly P; Lo, Kwok Wai; Chui, Yiu Loon; Li, Hoi Ming; Pang, Jesse Chung Sean; Tsao, Sai-Wah

2004-05-10

Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), a common cancer in Hong Kong. The EBV-encoded LMP1 protein is believed to play an important role in cell transformation. We have previously identified a prevalent LMP1 variant (2117-LMP1) that is expressed in 86% of primary NPC in Hong Kong. In this study, the biologic phenotypes induced by 2117-LMP1 were compared with those of the prototypic B95.8-LMP1 in an immortalized nasopharyngeal epithelial cell line, NP69. The 2117-LMP1 could induce cell proliferation and resistance to apoptosis induced by growth factor deprivation. Expression of 2117-LMP1 also suppressed expression of p16, p21 and Bax but induced expression of CDK2 and A20. Compared with B95.8-LMP1, 2117-LMP1 could induce a higher migration ability in NP69 cells but was less efficient in inducing morphologic changes, anchorage-independent growth and cell invasion. Relatively weaker ability of 2117-LMP1 than B95.8-LMP1 in upregulation of vimentin, VEGF and MMP9 as well as in downregulation of E-cadherin was observed. 2117-LMP1 could activate higher level of NF-kappaB activity in HEK 293 cells than B95.8-LMP1. The present study supports a role of 2117-LMP1 in NPC development by enhancing cell proliferation, cell death inhibition and migration in premalignant nasopharyngeal epithelial cells. Furthermore, our study reveals significant functional differences between 2117-LMP1 and the prototypic B95.8-LMP1. Our results provide insights into the pathologic significance of this prevalent LMP1 variant, 2117-LMP1, in the development of NPC in the Hong Kong population. Copyright 2004 Wiley-Liss, Inc.

Nasopharyngeal and Adenoid Colonization by Haemophilus influenzae and Haemophilus parainfluenzae in Children Undergoing Adenoidectomy and the Ability of Bacterial Isolates to Biofilm Production

PubMed Central

Kosikowska, Urszula; Korona-Głowniak, Izabela; Niedzielski, Artur; Malm, Anna

2015-01-01

Abstract Haemophili are pathogenic or opportunistic bacteria often colonizing the upper respiratory tract mucosa. The prevalence of Haemophilus influenzae (with serotypes distribution), and H. parainfluenzae in the nasopharynx and/or the adenoid core in children with recurrent pharyngotonsillitis undergoing adenoidectomy was assessed. Haemophili isolates were investigated for their ability to biofilm production. Nasopharyngeal swabs and the adenoid core were collected from 164 children who underwent adenoidectomy (2–5 years old). Bacteria were identified by the standard methods. Serotyping of H. influenzae was performed using polyclonal and monoclonal antisera. Biofilm formation was detected spectrophotometrically using 96-well microplates and 0.1% crystal violet. Ninety seven percent (159/164) children who underwent adenoidectomy were colonized by Haemophilus spp. The adenoid core was colonized in 99.4% (158/159) children, whereas the nasopharynx in 47.2% (75/159) children (P < 0.0001). In 32% (51/159) children only encapsulated (typeable) isolates of H. influenzae were identified, in 22.6% (36/159) children only (nonencapsulated) H. influenzae NTHi (nonencapsulated) isolates were present, whereas 7.5% (12/159) children were colonized by both types. 14.5% (23/159) children were colonized by untypeable (rough) H. influenzae. In 22% (35/159) children H. influenzae serotype d was isolated. Totally, 192 isolates of H. influenzae, 96 isolates of H. parainfluenzae and 14 isolates of other Haemophilus spp. were selected. In 20.1% (32/159) children 2 or 3 phenotypically different isolates of the same species (H. influenzae or H. parainfluenzae) or serotypes (H. influenzae) were identified in 1 child. 67.2% (129/192) isolates of H. influenzae, 56.3% (54/96) isolates of H. parainfluenzae and 85.7% (12/14) isolates of other Haemophilus spp. were positive for biofilm production. Statistically significant differences (P = 0.0029) among H. parainfluenzae

Colonic inflammation increases the contribution of muscarinic M2 receptors to carbachol-induced contraction of the rat colon.

PubMed

Jragh, Dina M; Khan, Islam; Oriowo, Mabayoje A

2011-01-01

Carbachol-induced contraction of the rat colon is impaired in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. The main objective of this study was to examine the effect of colitis on the expression and function of muscarinic (M) receptor subtypes in the rat colon. Rats (n = 80) were treated with TNBS and used 5 days later for measurement of contractility, myeloperoxidase activity, histology and expression of muscarinic receptor isoforms using Western blot analysis. Carbachol produced concentration-dependent contractions of colonic segments from control (n = 40) and TNBS-treated (n = 40) rats with no significant difference in potency. However, the maximum response to carbachol was significantly reduced in colon segments of TNBS-treated rats. The selective muscarinic receptor antagonists 4-diphenylacetoxy-N-methyl piperidine (4-DAMP, M(3)), pirenzepine (M(1)) and methoctramine (M(2)) antagonized carbachol-induced contraction in control (9.1 ± 0.1, 6.7 ± 0.3 and 6.0 ± 0.1, respectively) and TNBS-treated rats (9.2 ± 0.2, 6.9 ± 0.2, 6.7 ± 0.2). The -logK(B) values in control rats are consistent with an action of carbachol on muscarinic M(3) receptors. There was no significant difference in -logK(B) values for 4-DAMP and pirenzepine in control and TNBS-treated rats, but methoctramine was fivefold more potent in TNBS-treated rats, possibly indicating an increased contribution of muscarinic M(2) receptors to carbachol-induced contraction in the inflamed colon. The expression of M(2) receptors was also significantly increased in colon segments from TNBS-treated rats, confirming the increased role of muscarinic M(2) receptors in the inflamed colon. The data show that while only M(3) receptors appeared to mediate carbachol-induced contraction in control segments, expression of both M(2) and M(3) receptors was increased in the inflamed rat colon. Copyright © 2011 S. Karger AG, Basel.

Preliminary study of diagnostic spectroscopic imaging for nasopharyngeal carcinoma

NASA Astrophysics Data System (ADS)

Li, Buhong; Xie, Shusen; Zhang, Xiaodong; Li, Depin

2003-12-01

The optical biopsy system for nasopharyngeal carcinoma based on the technique of laser-induced exogenous fluorescence has been successful developed. Ar+ laser was selected as the excitation light source based on the measurement of the Emission-Excitation Matrix of Hematoporphyrin Monomethyl Ether. Tissue-simulating optical phantoms diluted with different concentration of HMME were used to simulated nasopharyngeal carcinoma lesions in the performance test for the drug-fluorescence optical biopsy system, especially for the comparison of fluorescence image contrast between the excitation wavelength of 488nm and 514.5nm, respectively. Experimental results show that the fluorescence image contrast of simulated nasopharyngeal carcinoma lesions excited by the light at the wavelength of 488nm is about three fold higher than that at 514.5nm, and the sensitivity and resolution of the fluorescence and reflection twilight image can satisfy the needs for clinical diagnosis and localization.

Bile acids at neutral and acidic pH induce apoptosis and gene cleavages in nasopharyngeal epithelial cells: implications in chromosome rearrangement.

PubMed

Tan, Sang-Nee; Sim, Sai-Peng

2018-04-12

Chronic rhinosinusitis (CRS) increases the risk of developing nasopharyngeal carcinoma (NPC) while nasopharyngeal reflux is known to be one of the major aetiological factors of CRS. Bile acid (BA), the component of gastric duodenal contents, has been recognised as a carcinogen. BA-induced apoptosis was suggested to be involved in human malignancies. Cells have the potential and tendency to survive apoptosis. However, cells that evade apoptosis upon erroneous DNA repair may carry chromosome rearrangements. Apoptotic nuclease, caspase-activated deoxyribonuclease (CAD) has been implicated in mediating translocation in leukaemia. We hypothesised that BA-induced apoptosis may cause chromosome breaks mediated by CAD leading to chromosome rearrangement in NPC. This study targeted the AF9 gene located at 9p22 because 9p22 is one of the most common deletion sites in NPC. We tested the ability of BA at neutral and acidic pH in inducing phosphatidylserine (PS) externalisation, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) disruption, and caspase 3/7 activity in normal nasopharyngeal epithelial (NP69) and NPC (TWO4) cells. Inverse-PCR (IPCR) was employed to detect AF9 gene cleavages. To investigate the role of CAD in mediating these cleavages, caspase inhibition was performed. IPCR bands representing AF9 cleaved fragments were sequenced. BA-treated cells showed higher levels of PS externalisation, ROS production, MMP loss and caspase 3/7 activity than untreated control cells. The effect of BA in the induction of these intracellular events was enhanced by acid. BA at neutral and acidic pH also induced significant cleavage of the AF9 gene. These BA-induced gene cleavages were inhibited by Z-DEVD-FMK, a caspase-3 inhibitor. Intriguingly, a few chromosome breaks were identified within the AF9 region that was previously reported to participate in reciprocal translocation between the mixed lineage leukaemia (MLL) and AF9 genes in an acute

The Role of Influenza and Parainfluenza Infections in Nasopharyngeal Pneumococcal Acquisition Among Young Children

PubMed Central

Grijalva, Carlos G.; Griffin, Marie R.; Edwards, Kathryn M.; Williams, John V.; Gil, Ana I.; Verastegui, Hector; Hartinger, Stella M.; Vidal, Jorge E.; Klugman, Keith P.; Lanata, Claudio F.

2014-01-01

Background. Animal models suggest that influenza infection favors nasopharyngeal acquisition of pneumococci. We assessed this relationship with influenza and other respiratory viruses in young children. Methods. A case-control study was nested within a prospective cohort study of acute respiratory illness (ARI) in Andean children <3 years of age (RESPIRA-PERU study). Weekly household visits were made to identify ARI and obtain nasal swabs for viral detection using real-time reverse-transcription polymerase chain reaction. Monthly nasopharyngeal (NP) samples were obtained to assess pneumococcal colonization. We determined whether specific respiratory viral ARI episodes occurring within the interval between NP samples increased the risk of NP acquisition of new pneumococcal serotypes. Results. A total of 729 children contributed 2128 episodes of observation, including 681 pneumococcal acquisition episodes (new serotype, not detected in prior sample), 1029 nonacquisition episodes (no colonization or persistent colonization with the same serotype as the prior sample), and 418 indeterminate episodes. The risk of pneumococcal acquisition increased following influenza-ARI (adjusted odds ratio [AOR], 2.19; 95% confidence interval [CI], 1.02–4.69) and parainfluenza-ARI (AOR, 1.86; 95% CI, 1.15–3.01), when compared with episodes without ARI. Other viral infections (respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus) were not associated with acquisition. Conclusions. Influenza and parainfluenza ARIs appeared to facilitate pneumococcal acquisition among young children. As acquisition increases the risk of pneumococcal diseases, these observations are pivotal in our attempts to prevent pneumococcal disease. PMID:24621951

Tetrandrine Induces Apoptosis in Human Nasopharyngeal Carcinoma NPC-TW 039 Cells by Endoplasmic Reticulum Stress and Ca2+/Calpain Pathways.

PubMed

Liu, Kuo-Ching; Lin, Ya-Jing; Hsiao, Yung-Ting; Lin, Meng-Liang; Yang, Jiun-Long; Huang, Yi-Ping; Chu, Yung-Lin; Chung, Jing-Gung

2017-11-01

Tetrandrine is an alkaloid extracted from a traditional China medicine plant, and is considered part of food therapy as well. In addition, it has been widely reported to induce apoptotic cell death in many human cancer cells. However, the mechanism of Tetrandrine on human nasopharyngeal carcinoma cells (NPC) is still questioned. In our study, we examined whether Tetrandrine can induce apoptosis of NPC-TW 039 cells. We found that cell morphology was changed after treatment with different concentrations of Tetrandrine. Further, we indicated that the NPC-TW 039 cells viability decreased in a Tetrandrine dose-dependent manner. We also found that tetrandrine induced cell cycle arrest in G 0 /G 1 phase. Tetrandrine induced DNA condensation by DAPI staining as well. In addition, we found that Tetrandrine induced Ca 2+ release in the cytosol. At the same time, endoplasmic reticulum (ER) stress occurred. Then we used western blotting to examine the protein expression which is associated with mitochondria-mediated apoptotic pathways and caspase-dependent pathways. To further examine whether Ca 2+ was released or not with Tetrandrine induced-apoptosis, we used the chelator of Ca 2+ and showed that cell viability increased. At the same time, caspase-3 expression was decreased. Furthermore, confocal microscopy examination revealed that Tetrandrine induced expression of ER stress-related proteins GADD153 and GRP78. Our results indicate that Tetrandrine induces apoptosis through calcium-mediated ER stress and caspase pathway in NPC-TW 039 cells. In conclusion, Tetrandrine may could be used for treatment of human nasopharyngeal carcinoma in future. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Localized nasopharyngeal amyloidosis mimicking malignancy: A case report.

PubMed

Kim, Jong Seung; Kwon, Sam Hyun

2017-07-01

Nasopharyngeal amyloidosis is a benign, slowly progressive disease that is characterized by extracellular eosinophilic deposition. We report a rare case of localized nasopharyngeal amyloidosis. The initial chief complaint of this patient was frequent epistaxis and right aural fullness. The initial diagnosis was nasopharyngeal tumor. There is no universally effective medical treatment for nasopharyngeal amyloidosis but surgery can be an option. We performed careful observation with regular follow-up by nasopharyngoscopy and radiologic study. The patient reported no further complaints at 1-year follow-up and the lesion from nasopharyngeal amyloidosis was still present. Although it is rare, nasopharyngeal amyloidosis should be considered in the differential diagnosis of epistaxis, nasal obstruction, and otitis media with effusion, which are the main symptoms of nasopharyngeal carcinoma. In the absence of systemic disease, localized nasopharyngeal amyloidosis may be treated conservatively.

Hydrostatic pressure-induced colon trauma from a pool whip.

PubMed

Tong, T K; McGill, L; Tilden, S J

1989-03-01

Hydrostatic pressure-induced colon injury is a rare occurrence in the pediatric population. We present a case of massive hydroperitoneum following a pool whip-induced injury. Although tension pneumoperitoneum or hydroperitoneum is rare, prompt recognition and surgical intervention are essential.

Increased choline kinase activity in 1,2-dimethylhydrazine-induced rat colon cancer.

PubMed

Nakagami, K; Uchida, T; Ohwada, S; Koibuchi, Y; Morishita, Y

1999-11-01

Cancer cells acquire particular characteristics that benefit their proliferation. We previously reported that human colon cancers examined had increased choline kinase activity and phosphocholine levels. The elevated phosphocholine levels were in part due to both activation of choline kinase and increased choline kinase alpha protein levels. In this report, we analyzed choline kinase, which catalyzes the phosphorylation of choline to produce phosphocholine, in rat 1,2-dimethylhydrazine (DMH)-induced colon cancer. This study is the first to demonstrate increased choline kinase alpha enzymatic activity, protein levels, and mRNA levels in DMH-induced colon cancer as well as human colon cancer, although phosphocholine was not increased in DMH-induced rat cancer. The increase in the mRNA level was partly due to an increase in the transcription of the choline kinase alpha gene. The increased choline kinase activity may be a specific characteristic acquired by cancer cells that benefits their proliferation.

Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice

PubMed Central

Dinh, Chi H. L.; Yu, Yinghua; Szabo, Alexander; Zhang, Qingsheng; Zhang, Peng; Huang, Xu-Feng

2016-01-01

Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora. PMID:26920068

Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice.

PubMed

Dinh, Chi H L; Yu, Yinghua; Szabo, Alexander; Zhang, Qingsheng; Zhang, Peng; Huang, Xu-Feng

2016-04-01

Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora. © 2016 The Histochemical Society.

General Information about Nasopharyngeal Cancer

MedlinePlus

... Nasopharyngeal Cancer Treatment (Adult) (PDQ®)–Patient Version General Information About Nasopharyngeal Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Development of the Nasopharyngeal Microbiota in Infants with Cystic Fibrosis.

PubMed

Prevaes, Sabine M P J; de Winter-de Groot, Karin M; Janssens, Hettie M; de Steenhuijsen Piters, Wouter A A; Tramper-Stranders, Gerdien A; Wyllie, Anne L; Hasrat, Raiza; Tiddens, Harm A; van Westreenen, Mireille; van der Ent, Cornelis K; Sanders, Elisabeth A M; Bogaert, Debby

2016-03-01

Cystic fibrosis (CF) is characterized by early structural lung disease caused by pulmonary infections. The nasopharynx of infants is a major ecological reservoir of potential respiratory pathogens. To investigate the development of nasopharyngeal microbiota profiles in infants with CF compared with those of healthy control subjects during the first 6 months of life. We conducted a prospective cohort study, from the time of diagnosis onward, in which we collected questionnaires and 324 nasopharynx samples from 20 infants with CF and 45 age-matched healthy control subjects. Microbiota profiles were characterized by 16S ribosomal RNA-based sequencing. We observed significant differences in microbial community composition (P < 0.0002 by permutational multivariate analysis of variance) and development between groups. In infants with CF, early Staphylococcus aureus and, to a lesser extent, Corynebacterium spp. and Moraxella spp. dominance were followed by a switch to Streptococcus mitis predominance after 3 months of age. In control subjects, Moraxella spp. enrichment occurred throughout the first 6 months of life. In a multivariate analysis, S. aureus, S. mitis, Corynebacterium accolens, and bacilli were significantly more abundant in infants with CF, whereas Moraxella spp., Corynebacterium pseudodiphtericum and Corynebacterium propinquum and Haemophilus influenzae were significantly more abundant in control subjects, after correction for age, antibiotic use, and respiratory symptoms. Antibiotic use was independently associated with increased colonization of gram-negative bacteria such as Burkholderia spp. and members of the Enterobacteriaceae bacteria family and reduced colonization of potential beneficial commensals. From diagnosis onward, we observed distinct patterns of nasopharyngeal microbiota development in infants with CF under 6 months of age compared with control subjects and a marked effect of antibiotic therapy leading toward a gram-negative microbial

Diffusion tensor imaging and 1H-MRS study on radiation-induced brain injury after nasopharyngeal carcinoma radiotherapy.

PubMed

Wang, H-Z; Qiu, S-J; Lv, X-F; Wang, Y-Y; Liang, Y; Xiong, W-F; Ouyang, Z-B

2012-04-01

To investigate the metabolic characteristics of the temporal lobes following radiation therapy for nasopharyngeal carcinoma using diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H-MRS). DTI and (1)H-MRS were performed in 48 patients after radiotherapy for nasopharyngeal carcinoma and in 24 healthy, age-matched controls. All patients and controls had normal findings on conventional MRI. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), three eigenvalues λ1, λ2, λ3, N-acetylaspartic acid (NAA)/choline (Cho), NAA/creatinine (Cr), and Cho/Cr were measured in both temporal lobes. Patients were divided into three groups according to time after completion of radiotherapy: group 1, less than 6 months; group 2, 6-12 months; group 3, more than 12 months. Mean values for each parameter were compared using one-way analysis of variance (ANOVA). Mean FA in group 1 was significantly lower compared to group 3 and the control group (p < 0.05). Group-wise comparisons of apparent diffusion coefficient (ADC) values among all the groups were not significantly different. Eigenvalue λ1 was significantly lower in groups 1 and 3 compared to the control group (p < 0.05). NAA/Cho and NAA/Cr were significantly lower in each group compared to the control group (p < 0.01 for both). The decrease in NAA/Cho was greatest in group 1. There were no significant between-group differences regarding Cho/Cr. A combination of DTI and (1)H-MRS can be used to detect radiation-induced brain injury, in patients treated for nasopharyngeal carcinoma. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Maternal Antibiotic-Induced Early Changes in Microbial Colonization Selectively Modulate Colonic Permeability and Inducible Heat Shock Proteins, and Digesta Concentrations of Alkaline Phosphatase and TLR-Stimulants in Swine Offspring

PubMed Central

Arnal, Marie-Edith; Zhang, Jing; Erridge, Clett; Smidt, Hauke; Lallès, Jean-Paul

2015-01-01

Elevated intake of high energy diets is a risk factor for the development of metabolic diseases and obesity. High fat diets cause alterations in colonic microbiota composition and increase gut permeability to bacterial lipopolysaccharide, and subsequent low-grade chronic inflammation in mice. Chronic inflammatory bowel diseases are increasing worldwide and may involve alterations in microbiota-host dialog. Metabolic disorders appearing in later life are also suspected to reflect changes in early programming. However, how the latter affects the colon remains poorly studied. Here, we hypothesized that various components of colonic physiology, including permeability, ion exchange and protective inducible heat shock proteins (HSP) are influenced in the short- and long-terms by early disturbances in microbial colonization. The hypothesis was tested in a swine model. Offspring were born to control mothers (n = 12) or mothers treated with the antibiotic (ATB) amoxicillin around parturition (n = 11). Offspring were slaughtered between 14 and 42 days of age to study short-term effects. For long-term effects, young adult offspring from the same litters consumed a normal or a palm oil-enriched diet for 4 weeks between 140 and 169 days of age. ATB treatment transiently modified maternal fecal microbiota although the minor differences observed for offspring colonic microbiota were nonsignificant. In the short-term, consistently higher HSP27 and HSP70 levels and transiently increased horseradish peroxidase permeability in ATB offspring colon were observed. Importantly, long-term consequences included reduced colonic horseradish peroxidase permeability, and increased colonic digesta alkaline phosphatase (AP) and TLR2- and TLR4-stimulant concentrations in rectal digesta in adult ATB offspring. Inducible HSP27 and HSP70 did not change. Interactions between early ATB treatment and later diet were noted for paracellular permeability and concentrations of colonic digesta AP. In

Maternal antibiotic-induced early changes in microbial colonization selectively modulate colonic permeability and inducible heat shock proteins, and digesta concentrations of alkaline phosphatase and TLR-stimulants in swine offspring.

PubMed

Arnal, Marie-Edith; Zhang, Jing; Erridge, Clett; Smidt, Hauke; Lallès, Jean-Paul

2015-01-01

Elevated intake of high energy diets is a risk factor for the development of metabolic diseases and obesity. High fat diets cause alterations in colonic microbiota composition and increase gut permeability to bacterial lipopolysaccharide, and subsequent low-grade chronic inflammation in mice. Chronic inflammatory bowel diseases are increasing worldwide and may involve alterations in microbiota-host dialog. Metabolic disorders appearing in later life are also suspected to reflect changes in early programming. However, how the latter affects the colon remains poorly studied. Here, we hypothesized that various components of colonic physiology, including permeability, ion exchange and protective inducible heat shock proteins (HSP) are influenced in the short- and long-terms by early disturbances in microbial colonization. The hypothesis was tested in a swine model. Offspring were born to control mothers (n = 12) or mothers treated with the antibiotic (ATB) amoxicillin around parturition (n = 11). Offspring were slaughtered between 14 and 42 days of age to study short-term effects. For long-term effects, young adult offspring from the same litters consumed a normal or a palm oil-enriched diet for 4 weeks between 140 and 169 days of age. ATB treatment transiently modified maternal fecal microbiota although the minor differences observed for offspring colonic microbiota were nonsignificant. In the short-term, consistently higher HSP27 and HSP70 levels and transiently increased horseradish peroxidase permeability in ATB offspring colon were observed. Importantly, long-term consequences included reduced colonic horseradish peroxidase permeability, and increased colonic digesta alkaline phosphatase (AP) and TLR2- and TLR4-stimulant concentrations in rectal digesta in adult ATB offspring. Inducible HSP27 and HSP70 did not change. Interactions between early ATB treatment and later diet were noted for paracellular permeability and concentrations of colonic digesta AP. In

Colonic responses to Lactobacillus farciminis treatment in trinitrobenzene sulphonic acid-induced colitis in rats.

PubMed

Lamine, F; Eutamène, H; Fioramonti, J; Buéno, L; Théodorou, V

2004-12-01

It has recently been shown that Lactobacillus farciminis treatment exerts an anti-inflammatory effect in trinitrobenzene sulphonic acid (TNBS)-induced colitis partly through a nitric oxide release by this strain. The aim of this study was to evaluate whether L. farciminis treatment shares also the general mechanisms of action involved in the beneficial effect of probiotics in the colonic inflammatory process. Rats received L. farciminis for 15 days before and 4 days after intracolonic administration of TNBS or vehicle. The following parameters were evaluated: macroscopic damage of colonic mucosa, myeloperoxidase activity, cytokine mucosal levels, bacterial profile in colonic content and mucosa, bacterial translocation and colonic paracellular permeability. In the absence of TNBS, L. farciminis treatment reduced colonic paracellular permeability and increased the IL-10 level in the colonic wall. TNBS administration induced colonic macroscopic damage, associated with an increase of myeloperoxidase activity, bacterial translocation, colonic paracellular permeability and IL-1beta mucosal level, and a decrease in IL-10 mucosal level. Moreover, the bacterial profile of colonic content and mucosa was modified. All these alterations were abolished or significantly reduced by L. farciminis treatment. As previously shown, L. farciminis treatment improves TNBS-induced colitis. This study indicates that, in addition to the nitric oxide released by this bacterial strain, the anti-inflammatory action of L. farciminis involves also normalization of colonic microflora, prevention of bacterial translocation, enhancement of barrier integrity and a decrease in the IL-1beta mucosal level.

Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer

ClinicalTrials.gov

2018-05-23

Nasopharyngeal Nonkeratinizing Carcinoma; Recurrent Nasopharynx Carcinoma; Stage III Nasopharyngeal Carcinoma AJCC v7; Stage IV Nasopharyngeal Carcinoma AJCC v7; Stage IVA Nasopharyngeal Carcinoma AJCC v7; Stage IVB Nasopharyngeal Carcinoma AJCC v7; Stage IVC Nasopharyngeal Carcinoma AJCC v7

What's New in Nasopharyngeal Cancer Research and Treatment?

MedlinePlus

... and Treatment? Nasopharyngeal Cancer About Nasopharyngeal Cancer What's New in Nasopharyngeal Cancer Research and Treatment? Research into ... the world where this cancer is common. Treatment New surgical techniques Advances in the field of skull ...

Radiation-induced functional connectivity alterations in nasopharyngeal carcinoma patients with radiotherapy

PubMed Central

Ma, Qiongmin; Wu, Donglin; Zeng, Ling-Li; Shen, Hui; Hu, Dewen; Qiu, Shijun

2016-01-01

Abstract The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale. The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores. Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA. The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment. PMID:27442663

Radiation-induced functional connectivity alterations in nasopharyngeal carcinoma patients with radiotherapy.

PubMed

Ma, Qiongmin; Wu, Donglin; Zeng, Ling-Li; Shen, Hui; Hu, Dewen; Qiu, Shijun

2016-07-01

The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale.The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores.Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA.The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment.

Fermented dairy products modulate Citrobacter rodentium-induced colonic hyperplasia.

PubMed

Collins, James W; Chervaux, Christian; Raymond, Benoit; Derrien, Muriel; Brazeilles, Rémi; Kosta, Artemis; Chambaud, Isabelle; Crepin, Valerie F; Frankel, Gad

2014-10-01

We evaluated the protective effects of fermented dairy products (FDPs) in an infection model, using the mouse pathogen Citrobacter rodentium (CR). Treatment of mice with FDP formulas A, B, and C or a control product did not affect CR colonization, organ specificity, or attaching and effacing lesion formation. Fermented dairy product A (FDP-A), but neither the supernatant from FDP-A nor β-irradiated (IR) FDP-A, caused a significant reduction in colonic crypt hyperplasia and CR-associated pathology. Profiling the gut microbiota revealed that IR-FDP-A promoted higher levels of phylotypes belonging to Alcaligenaceae and a decrease in Lachnospiraceae (Ruminococcus) during CR infection. Conversely, FDP-A prevented a decrease in Ruminococcus and increased Turicibacteraceae (Turicibacter). Importantly, loss of Ruminococcus and Turicibacter has been associated with susceptibility to dextran sodium sulfate-induced colitis. Our results demonstrate that viable bacteria in FDP-A reduced CR-induced colonic crypt hyperplasia and prevented the loss of key bacterial genera that may contribute to disease pathology. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

FAMM Flap in Reconstructing Postsurgical Nasopharyngeal Airway Stenosis

PubMed Central

Nangole, Ferdinand Wanjala; Khainga, Stanley Ominde

2014-01-01

Introduction. Postsurgical nasopharyngeal airway stenosis can be a challenge to manage. The stenosis could be as a result of any surgical procedure in the nasopharyngeal region that heals extensive scarring and fibrosis. Objective. To evaluate patients with nasopharyngeal stenosis managed with FAMM flap. Study Design. Prospective study of patients with nasopharyngeal stenosis at the Kenyatta National Hospital between 2010 and 2013 managed with FAMM flap. Materials and Methods. Patients with severe nasopharyngeal airway stenosis were reviewed and managed with FAMM flaps at the Kenyatta National Hospital. Postoperatively they were assessed for symptomatic improvement in respiratory distress, patency of the nasopharyngeal airway, and donor site morbidity. Results. A total of 8 patients were managed by the authors in a duration of 4 years with nasopharyngeal stenosis. Five patients were managed with unilateral FAMM flaps in a two-staged surgical procedure. Four patients had complete relieve of the airway obstruction with a patent airway created. One patient had a patent airway created though with only mild improvement in airway obstruction. Conclusion. FAMM flap provides an alternative in the management of postsurgical severe nasopharyngeal stenosis. It is a reliable flap that is easy to raise and could provide adequate epithelium for the stenosed pharynx. PMID:25328699

Nasopharyngeal culture

MedlinePlus

Culture - nasopharyngeal; Swab for respiratory viruses; Swab for staph carriage ... test identifies viruses and bacteria that cause upper respiratory tract symptoms. These include: Bordetella pertussis Neisseria meningitidis ...

Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.

PubMed

He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

2014-02-01

Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.

Changes in colonic motility induced by sennosides in dogs: evidence of a prostaglandin mediation.

PubMed Central

Staumont, G; Fioramonti, J; Frexinos, J; Bueno, L

1988-01-01

The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter and a polyethylene catheter implanted in a branch of the right colonic artery. Oral sennosides (30 mg/kg) inhibited colonic motility for 12 to 18 h after a three to six hours delay, and associated with giant contractions and diarrhoea. The minimal oral dose of sennosides to produce such changes varied from 5 to 15 mg/kg. Intracolonic sennosides at the minimal effective dose and at 30 mg/kg reproduced the effects of oral sennosides, but with a shorter latency (0.5-1.5 h). Intracolonic PGE2 (100 micrograms/kg) in viscous gel medium or intra-arterial PGE2 (10 micrograms/h) inhibited colonic motility and induced giant contractions often associated with defecation. The colonic motor changes induced by intracolonic sennosides at the minimal effective dose, but not those induced by intracolonic PGE2, were blocked by intra-arterial indomethacin (10 micrograms/h) or piroxicam (5 micrograms/h). These results suggest that colonic motor actions of sennosides are mediated through a local prostaglandins synthesis, as they were blocked by cyclooxygenase inhibitor and reproduced by PGE2. PMID:3197991

The novel HDAC inhibitor AR-42-induced anti-colon cancer cell activity is associated with ceramide production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Weihong; Xu, Bin; Yao, Yiting

In the current study, we investigated the potential activity of AR-42, a novel histone deacetylase (HDAC) inhibitor, against colon cancer cells. Our in vitro results showed that AR-42 induced ceramide production, exerted potent anti-proliferative and pro-apoptotic activities in established (SW-620 and HCT-116 lines) and primary human colon cancer cells. Exogenously-added sphingosine 1-phosphate (S1P) suppressed AR-42-induced activity, yet a cell-permeable ceramide (C4) facilitated AR-42-induced cytotoxicity against colon cancer cells. In addition, AR-42-induced ceramide production and anti-colon cancer cell activity were inhibited by the ceramide synthase inhibitor fumonisin B1, but were exacerbated by PDMP, which is a ceramide glucosylation inhibitor. In vivo, oral administrationmore » of a single dose of AR-42 dramatically inhibited SW-620 xenograft growth in severe combined immunodeficient (SCID) mice, without inducing overt toxicities. Together, these results show that AR-42 dramatically inhibits colon cancer cell proliferation in vitro and in vivo, and ceramide production might be the key mechanism responsible for its actions. - Highlights: • AR-42 is anti-proliferative against primary/established colon cancer cells. • AR-42 induces significant apoptotic death in primary/established colon cancer cells. • Ceramide production mediates AR-42-induced cytotoxicity in colon cancer cells. • AR-42 oral administration potently inhibits SW-620 xenograft growth in SCID mice.« less

Nasopharyngeal carcinoma.

PubMed

Kamran, Sophia C; Riaz, Nadeem; Lee, Nancy

2015-07-01

Nasopharyngeal carcinoma is uncommon in the United States, with only 0.2 to 0.5 cases per 100,00 people; this is in contrast to southern China and Hong Kong, where the incidence is 25 to 50 per 100,000 people. There is a potential link between Epstein-Barr virus and the development of nasopharyngeal carcinoma. Radiotherapy alone as a single modality leads to similar 10-year survival rates in United States, Denmark, and Hong Kong (34%, 37%, and 43%, respectively). Multiple studies have shown an advantage to concurrent chemoradiation in the treatment of advanced disease. Radiation therapy remains the mainstay of salvage therapy, and modern techniques have allowed clinicians to achieve adequate local control without excessive toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis.

PubMed

Gavert, Nancy; Sheffer, Michal; Raveh, Shani; Spaderna, Simone; Shtutman, Michael; Brabletz, Thomas; Barany, Francis; Paty, Phillip; Notterman, Daniel; Domany, Eytan; Ben-Ze'ev, Avri

2007-08-15

L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of beta-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases. We identified ADAM10, a metalloproteinase that cleaves the L1-CAM extracellular domain, as a novel target gene of beta-catenin-TCF signaling. ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples. Expression of these genes in normal colon epithelium was low. These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy.

MET inhibitor PHA-665752 suppresses the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Tongxin; Li, Qi; Sun, Quanquan

2014-06-20

Highlights: • We demonstrated that irradiation induced MET overexpression and activation. • The aberrant MET signal mediated by HGF induced proliferation and radioresistance of NPC cells. • MET inhibitor PHA-665752 effectively suppressed HGF induced cell proliferation and radioresistance in NPC cells. • PHA-665752 suppressed the three downstream pathway of HGF/MET signal in a dose-dependent manner. - Abstract: Although ionizing radiation (IR) has provided considerable improvements in nasopharyngeal carcinoma (NPC), in subsets of patients, radioresistance is still a major problem in the treatment. In this study, we demonstrated that irradiation induced MET overexpression and activation, and the aberrant MET signal mediatedmore » by hepatocyte growth factor (HGF) induced radioresistance. We also found that MET inhibitor PHA-665752 effectively suppressed HGF induced cell proliferation and radioresistance in NPC cells. Further investigation indicated that PHA-665752 suppressed the phosphorylation of the Akt, ERK1/2, and STAT3 proteins in a dose-dependent manner. Our data indicated that the combination of IR with a MET inhibitor, such as PHA-665752, might be a promising therapeutic strategy for NPC.« less

α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon

PubMed Central

Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

2011-01-01

AIM: To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. METHODS: Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. RESULTS: Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. CONCLUSION: GCs promote the development of rat colon

HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Haidari, Amr A.; Syk, Ingvar; Thorlacius, Henrik, E-mail: henrik.thorlacius@med.lu.se

2014-03-28

Highlights: • Simvastatin blocked CCL17-induced and CCR4-dependent RhoA activation in HT29 cells. • CCL17/CCR4-mediated migration of colon cancer cells was antagonised by simvastatin. • Cell migration recovered by adding Mevalonate and geranylgeranyl pyrophosphate. • Targeting HMG-CoA reductase might be useful to inhibit colon cancer metastasis. - Abstract: Background: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects. Aim: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration. Methods: Migration assays were performed to evaluatemore » CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay. Results: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Conclusions: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell

Efficient Immortalization of Primary Nasopharyngeal Epithelial Cells for EBV Infection Study

PubMed Central

Yip, Yim Ling; Pang, Pei Shin; Deng, Wen; Tsang, Chi Man; Zeng, Musheng; Hau, Pok Man; Man, Cornelia; Jin, Yuesheng; Yuen, Anthony Po Wing; Tsao, Sai Wah

2013-01-01

Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic

21 CFR 882.1340 - Nasopharyngeal electrode.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasopharyngeal electrode. 882.1340 Section 882.1340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1340 Nasopharyngeal electrode...

21 CFR 882.1340 - Nasopharyngeal electrode.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasopharyngeal electrode. 882.1340 Section 882.1340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1340 Nasopharyngeal electrode...

21 CFR 868.5100 - Nasopharyngeal airway.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway. (a...

21 CFR 868.5100 - Nasopharyngeal airway.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway. (a...

21 CFR 868.5100 - Nasopharyngeal airway.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway. (a...

21 CFR 868.5100 - Nasopharyngeal airway.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway. (a...

Pathogenic bacteria induce colonic PepT1 expression: an implication in host defense response

PubMed Central

Nguyen, Hang Thi Thu; Dalmasso, Guillaume; Powell, Kimberly R.; Yan, Yutao; Bhatt, Shantanu; Kalman, Daniel; Sitaraman, Shanthi; Merlin, Didier

2009-01-01

Background & Aims Expression of the di/tripeptide transporter PepT1 has been observed in the colon under inflammatory conditions, however, the inducing factors and underlying mechanisms remain unknown. Here, we address the effects of pathogenic bacteria on colonic PepT1 expression together with its functional consequences. Methods Human colonic HT29-Cl.19A cells were infected with the attaching and effacing (A/E) enteropathogenic E. coli (EPEC). Wild-type and PepT1 transgenic mice or cultured colonic tissues derived from these mice were infected with Citrobacter rodentium, a murine A/E pathogen related to EPEC. Results EPEC induced PepT1 expression and activity in HT29-Cl.19A cells by intimately attaching to host cells through lipid rafts. Induction of PepT1 expression by EPEC required the transcription factor Cdx2. PepT1 expression reduced binding of EPEC to lipid rafts, as well as activation of NF-κB and MAP kinase and production of IL-8. Accordingly, ex vivo and in vivo experiments revealed that C. rodentium induced colonic PepT1 expression and that, compared to their wild-type counterparts, PepT1 transgenic mice infected with C. rodentium exhibited decreased bacterial colonization, production of pro-inflammatory cytokines, and neutrophil infiltration into the colon. Conclusions Our findings demonstrate a molecular mechanism underlying the regulation of colonic PepT1 expression under pathological conditions and reveal a novel role for PepT1 in host defense via its capacity to modulate bacterial-epithelial interactions and intestinal inflammation. PMID:19549526

Surgical techniques in radiation induced temporal lobe necrosis in nasopharyngeal carcinoma patients.

PubMed

Alfotih, Gobran Taha Ahmed; Zheng, Mei Guang; Cai, Wang Qing; Xu, Xin Ke; Hu, Zhen; Li, Fang Cheng

2016-01-01

Radiation induced brain injury ranges from acute reversible edema to late, irreversible radiation necrosis. Radiation induced temporal lobe necrosis is associated with permanent neurological deficits and occasionally progresses to death. We present our experience with surgery on radiation induced temporal lobe necrosis (RTLN) in nasopharyngeal carcinoma (NPC) patients with special consideration of clinical presentation, surgical technique, and outcomes. This retrospective study includes 12 patients with RTLN treated by the senior author between January 2010 and December 2014. Patients initially sought medical treatment due to headache; other symptoms were hearing loss, visual deterioration, seizure, hemiparesis, vertigo, memory loss and agnosia. A temporal approach through a linear incision was performed for all cases. RTLN was found in one side in 7 patients, and bilaterally in 5. 4 patients underwent resection of necrotic tissue bilaterally and 8 patients on one side. No death occurred in this series of cases. There were no post-operative complications, except 1 patient who developed aseptic meningitis. All 12 patients were free from headache. No seizure occurred in patients with preoperative epilepsy. Other symptoms such as hemiparesis and vertigo improved in all patients. Memory loss, agnosia and hearing loss did not change post-operatively in all cases. The follow-up MR images demonstrated no recurrence of necrotic lesions in all 12 patients. Neurosurgical intervention through a temporal approach with linear incision is warranted in patients with radiation induced temporal lobe necrosis with significant symptoms and signs of increased intracranial pressure, minimum space occupying effect on imaging, or neurological deterioration despite conservative management. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis.

PubMed

Lai, Ching-Shu; Wu, Jia-Ching; Yu, Shih-Feng; Badmaev, Vladimir; Nagabhushanam, Kalyanam; Ho, Chi-Tang; Pan, Min-Hsiung

2011-12-01

Tetrahydrocurcumin (THC), a major metabolite of curcumin (CUR), has been demonstrated to be anti-cancerogenic and anti-angiogenic and prevents type II diabetes. In this present study, we investigated the chemopreventive effects and underlying molecular mechanisms of dietary administration of CUR and THC in azoxymethane (AOM)-induced colon carcinogenesis in mice. All mice were sacrificed at 6 and 23 wk, and colonic tissue was collected and examined. We found that dietary administration of both CUR and THC could reduce aberrant crypt foci and polyps formation, while THC showed a better inhibitory effect than CUR. At the molecular level, results from Western blot analysis and immunohistochemistry staining showed that dietary CUR and THC exhibited anti-inflammatory activity by decreasing the levels of inducible NOS and COX-2 through downregulation of ERK1/2 activation. In addition, both dietary CUR and THC significantly decreased AOM-induced Wnt-1 and β-catenin protein expression, as well as the phosphorylation of GSK-3β in colonic tissue. Moreover, dietary feeding with CUR and THC markedly reduced the protein level of connexin-43, an important molecule of gap junctions, indicating that both CUR and THC might interfer with the intercellular communication of crypt cells. Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary THC against AOM-induced colonic tumorigenesis. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts

PubMed Central

2014-01-01

Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Results Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. Conclusions The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities. PMID:24533833

Curcumin reverses attenuated carbachol-induced contraction of the colon in a rat model of colitis.

PubMed

Lubbad, Asmaa S; Oriowo, Mabayoje A; Khan, Islam

2009-01-01

Curcumin ameliorates colitis whether it reverses colitis-induced reduction in colonic contractility remains to be investigated. To investigate the effect of curcumin on colitis-induced reduction of carbachol-induced contraction in colon segments from rats treated with trinitrobenzenesulphonic acid. Colitis was induced in rats by intra rectal administration of trinitrobenzenesulphonic acid and followed for 5 days. A group of animals which received trinitobenzene sulphonic acids was treated with curcumin (100 mg/Kg and 200 mg/kg body weight) 2 hrs prior to induction of colitis. The controls received phosphate buffered saline in a similar fashion. Markers of inflammation and contractility of colon were assayed using standard procedures. Induction of colitis was associated with increased myeloperoxidase activity and malondialdehyde levels, gross histological changes characterized by infiltration of inflammatory cells. All these changes were prevented by treatment with curcumin (100 mg/kg). Treatment with curcumin also reduced the histological scores from 3.34+/-0.40 to 1.75+/-0.30 confirming an anti-inflammatory effect of curcumin in this experimental model of colitis. Colonic reactivity to carbachol was decreased in colitis affecting the maximum response but not sensitivity. Treatment with curcumin had no effect on sensitivity of the colon to carbachol in any of the preparations. Curcumin however reversed the decrease in carbachol-induced contraction associated with trinitrobenzenesulphonic acid treatment. The same dose of curcumin had no effect on either the potency of or the maximum response to carbachol in control rats. Tissue expression of NF-kB was increased in colon segments from trinitrobenzenesulphonic acid -treated rats and this was inhibited in rats treated with curcumin. Based on these findings it is concluded that curcumin prevented the reduction in carbachol-induced contraction in trinitrobenzenesulphonic acid -treated rats by modulating NF-kB signaling

Inhibition of autophagy by 3-MA enhances endoplasmic reticulum stress-induced apoptosis in human nasopharyngeal carcinoma cells.

PubMed

Song, Lele; Liu, Hao; Ma, Linyan; Zhang, Xudng; Jiang, Zhiwen; Jiang, Chenchen

2013-10-01

Radiotherapy and adjuvant cisplatin chemotherapy are the mainstream treatments for nasopharyngeal carcinoma (NPC), which effectively improve the outcome and reduce tumor recurrence. However, the resistance mechanism(s) involved in radiotherapy and chemotherapy, which is the main barrier in NPC treatment, remains undefined. Therefore, there is an urgent requirement for the identification of new therapeutic strategies or adjuvant drugs. In the present study, the effects of autophagy inhibitors on endoplasmic reticulum (ER) stress-induced autophagy was investigated. Combining 3-methyladenine (3-MA) with cisplatin (DDP), ionizing radiation (IR), 2-deoxy-D-glucose (2-DG) or tunicamycin (TM) resulted in enhanced cell death, as revealed by MTT and colony formation assays. Flow cytometry results demonstrated that the sensitivity of NPC cells to DDP- and IR-induced apoptosis was not significant. DDP, IR, 2-DG and TM induced ER stress and autophagy. Using fluorescence microscopy, 3-MA was identified to increase the apoptotic cell death induced by DDP, IR, 2-DG or TM. In addition, 3-MA inhibited the increased autophagy induced by DDP, IR, 2-DG or TM, as demonstrated by western blot analysis and immunocytochemistry results. Results of the present study indicate that autophagy acts as a protective mechanism response to the apoptosis induced by DDP, IR, 2-DG or TM.

Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia.

PubMed

Deschner, E E; Ruperto, J; Wong, G; Newmark, H L

1991-07-01

Dietary quercetin (QU) and rutin (RU), phenolic flavonoids commonly found in many fruits and vegetables, were provided to CF1 female mice for 50 weeks to assess the ability of these compounds to inhibit azoxymethanol (AOM)-induced colonic neoplasia. In addition to a control group fed an AIN 76A diet, five other groups received that diet to which was added either 0.1, 0.5 or 2.0% QU and 1.0 or 4.0% RU. Acute studies revealed that, among saline controls, no alteration of any proliferative parameters of colonic epithelial cells was observed among those groups receiving any dose of QU or RU. However, among the AOM-treated mice, both 2% QU and 4% RU significantly reduced hyperproliferation and inhibited the shift of S-phase cells to the middle and upper portion of crypts. Moreover, mice fed these concentrations of QU and RU had significantly fewer AOM-induced focal areas of dysplasia (FADs) than those fed the control diet (0.2 +/- 0.4 and 0.4 +/- 0.5 versus 3.6 +/- 2.3 respectively). Tumors occurred more frequently in the distal half of the colon, regardless of treatment. Compared with controls, mice fed 2% QU had a significantly reduced tumor incidence (25.0% versus 5.9%, P = 0.03). Those fed 4% RU showed only a trend toward inhibition (25% versus 9.7%, P = 0.11). Nevertheless, both 2% QU and 4% RU suppressed tumor multiplicity, i.e. fewer tumors/animal arose in these groups than in the AOM-treated control mice (1.2 versus 2.3, P = 0.005; 1.1 versus 2.3, P = 0.003 respectively). Clearly, QU and RU exhibit significant activity in reducing AOM-induced hyperproliferation of colonic epithelial cells and FAD incidence. This behavior successfully forecast the ability of both flavonoids to suppress tumor multiplicity and ultimately tumor development.

Nasopharyngeal bacterial load as a marker for rapid and easy diagnosis of invasive pneumococcal disease in children from Mozambique

PubMed Central

Lanaspa, Miguel; Henares, Desiree; Perez-Arguello, Amaresh; Madrid, Lola; Balcells, Reyes; Acacio, Sozinho; Andres-Franch, Maria; Marcos, Maria Angeles; Valero-Rello, Ana

2017-01-01

Background Current diagnostic methods for detection of Streptococcus pneumoniae in children with suspected invasive pneumococcal disease have limitations of accuracy, timeliness, and patient convenience. This study aimed to determine the performance of pneumococcal load quantified with a real-time polymerase-chain reaction in nasopharyngeal samples to diagnose invasive pneumococcal disease in children. Methods Matched case-control study of patients <5 years of age with invasive pneumococcal disease admitted to the Manhiça District Hospital (Mozambique) and asymptomatic controls recruited in different periods between 2006 and 2014. Cases were confirmed by a positive bacterial culture for S. pneumoniae in blood or cerebrospinal fluid. Nasopharyngeal aspirates were collected from cases and controls and pneumococcal density was quantified by lytA real-time polymerase-chain reaction. Results Thirty cases (median age 12.8 months) and sixty controls (median age 11.7 months) were enrolled and 70% of them were male. Nasopharyngeal pneumococcal carriage was high in both groups: 28/30 (93.3%) for cases vs. 53/60 (88.3%) for controls (p = 0.71). Mean nasopharyngeal pneumococcal load was identified as a marker for invasive pneumococcal disease (7.0 log10 copies/mL in cases vs. 5.8 log10 copies/mL in controls, p<0.001) and showed good discriminatory power (AUC-ROC: 82.1%, 95% CI 72.5%-91.8%). A colonization density of 6.5 log10 copies/mL was determined as the optimal cut-off value to distinguish cases from controls (sensitivity 75.0%, specificity 73.6%). Conclusion Use of non-invasive nasopharyngeal aspirates coupled with rapid and accurate quantification of pneumococcal load by real-time polymerase chain reaction has the potential to become a useful surrogate marker for early diagnosis of invasive pneumococcal disease in children. PMID:28910402

Prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae in China: a meta-analysis.

PubMed

Wang, Lin; Fu, Jinjian; Liang, Zhuoxin; Chen, Jichang

2017-12-13

of nasopharyngeal carriage among children was high in China. PCV7 immunization was found to be associated with reduction of nasopharyngeal colonization of S. pneumoniae. Conjugate vaccination coverage was slightly affected by the introduction of PCV7 into China because of low vaccination rate. The government should implement timely adjusted conjugate vaccination strategies based on our findings.

Activation of Intestinal Human Pregnane X Receptor Protects against Azoxymethane/Dextran Sulfate Sodium–Induced Colon Cancer

PubMed Central

Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro; Okamoto, Minoru; Qu, Aijuan; Tanaka, Naoki; Kimura, Shioko

2014-01-01

The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)–induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival rate of PXR-humanized mice, but not wild-type or Pxr-null mice. These data indicated a human PXR–dependent therapeutic chemoprevention of rifaximin toward AOM/DSS-induced colon cancer. Nuclear factor κ-light-chain-enhancer of activated B cells–mediated inflammatory signaling was upregulated in AOM/DSS-treated mice, and inhibited by rifaximin in PXR-humanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. In vitro cell-based assays further revealed that rifaximin regulated cell apoptosis and cell cycle in a human PXR-dependent manner. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events. PMID:25277138

A Giant Juvenile Nasopharyngeal Angiofibroma

PubMed Central

Yüce, Salim; Uysal, İsmail Önder; Doğan, Mansur; Polat, Kerem; Şalk, İsmail; Müderris, Suphi

2012-01-01

Juvenile nasopharyngeal angiofibroma (JNA) are locally growing highly vascular tumours. They are treated primarily by surgical excision ranging from open approach to endoscopic approach. We presented a 20-year-old male with a giant nasopharyngeal juvenile angiofibroma obliterating the pterygopalatine fossa bilaterally, invasing the sphenoid bone and extending to the left nasal passage. His complaints were epistaxis and nasal obstruction. After embolization, the patient was treated surgically with endoscopic approach and discharged as cured without any complication. PMID:23714961

SND1, a component of RNA-induced silencing complex, is up-regulated in human colon cancers and implicated in early stage colon carcinogenesis.

PubMed

Tsuchiya, Naoto; Ochiai, Masako; Nakashima, Katsuhiko; Ubagai, Tsuneyuki; Sugimura, Takashi; Nakagama, Hitoshi

2007-10-01

Colon cancers have been shown to develop after accumulation of multiple genetic and epigenetic alterations with changes in global gene expression profiles, contributing to the establishment of widely diverse phenotypes. Transcriptional and posttranscriptional regulation of gene expression by small RNA species, such as the small interfering RNA and microRNA and the RNA-induced silencing complex (RISC), is currently drawing major interest with regard to cancer development. SND1, also called Tudor-SN and p100 and recently reported to be a component of RISC, is among the list of highly expressed genes in human colon cancers. In the present study, we showed remarkable up-regulation of SND1 mRNA in human colon cancer tissues, even in early-stage lesions, and also in colon cancer cell lines. When mouse Snd1 was stably overexpressed in IEC6 rat intestinal epithelial cells, contact inhibition was lost and cell growth was promoted, even after the cells became confluent. Intriguingly, IEC6 cells with high levels of Snd1 also showed an altered distribution of E-cadherin from the cell membrane to the cytoplasm, suggesting loss of cellular polarity. Furthermore, the adenomatous polyposis coli (Apc) protein was coincidentally down-regulated, with no significant changes in the Apc mRNA level. Immunohistochemical analysis using chemically induced colonic lesions developed in rats revealed overexpression of Snd1 not only in colon cancers but also in aberrant crypt foci, putative precancerous lesions of the colon. Up-regulation of SND1 may thus occur at a very early stage in colon carcinogenesis and contribute to the posttranscriptional regulation of key players in colon cancer development, including APC and beta-catenin.

Oxymatrine induces nasopharyngeal cancer cell death through inhibition of PI3K/AKT and NF‑κB pathways.

PubMed

Ni, Zhili; Yi, Jingmei

2017-12-01

Oxymatrine may inhibit tumor cell proliferation, induce cell cycle arrest, promote apoptosis, induce tumor cell differentiation and fight against tumor angiogenesis, as well as inhibit tumor invasion and metastasis. The present study aimed to investigate the anticancer effects of oxymatrine on nasopharyngeal cancer (NPC) cell death, and the underlying molecular mechanisms of these effects. NPC HK‑1 cells were incubated overnight and treated with oxymatrine (0, 2, 4, 6 and 8 mg/ml) for 1, 2 or 3 days. The results demonstrated that oxymatrine significantly inhibited NPC cell proliferation in a time‑ and dose‑dependent manner. Oxymatrine treatment also induced apoptosis, induced the activities of caspase‑3 and caspase‑9, promoted p53 and Bax protein expression, and suppressed cyclin D protein expression in these cells. The protein expression levels of phosphoinositide 3 kinase (PI3K), phosphorylated (p)‑AKT, p‑mammalian target of rapamycin, p‑p70 ribosomal protein S6 kinase and nuclear factor (NF)‑κB were significantly downregulated by oxymatrine treatment. In conclusion, results from the present study suggested that oxymatrine may induce NPC cell death through the inhibition of PI3K/AKT and NF‑κB signaling pathways.

Oleuropein Prevents Azoxymethane-Induced Colon Crypt Dysplasia and Leukocytes DNA Damage in A/J Mice.

PubMed

Sepporta, Maria Vittoria; Fuccelli, Raffaela; Rosignoli, Patrizia; Ricci, Giovanni; Servili, Maurizio; Fabiani, Roberto

2016-08-19

Previous studies have shown that the precursor of olive oil secoiridoids, Oleuropein (OL) has several in vitro chemopreventive properties. OL inhibits proliferation and induces apoptosis in breast, thyroid, prostate, and colorectal cancer (CRC) cells. Much less is known about the effects of OL on animal models of carcinogenesis. In this study, we investigated the ability of OL to prevent the azoxymethane (AOM)-induced colon cancer upset and DNA damage in mice. Animals, fed with a basal diet either enriched or not with OL (125 mg/kg), were injected with AOM (10 mg/kg, once a week for 6 weeks) and sacrificed after either 7 weeks for histological analysis of colon crypt dysplasia and evaluation of DNA damage in leukocytes or 17 weeks for counting the macroscopically observable colon tumors. An OL-enriched diet prevented the AOM-induced preneoplastic lesions in different colon segments, reducing the severity of crypt dysplasia and DNA damage in peripheral leukocytes. In addition, OL significantly reduced the AOM-induced tumor incidence from 57% to 14% (P < .05, chi-square test) in the medial colon segment. This study shows that OL is able to prevent CRC and DNA damage in mice treated with the carcinogen AOM. These results stimulate further human cancer prevention studies with OL-enriched food supplements that are actually available on the market.

Dietary selenium protects adiponectin knockout mice against chronic inflammation induced colon cancer.

PubMed

Saxena, Arpit; Fayad, Raja; Kaur, Kamaljeet; Truman, Samantha; Greer, Julian; Carson, James A; Chanda, Anindya

2017-04-03

Selenium (Se) is an essential dietary micronutrient that has been examined for protection against different types of cancers including colon cancer. Despite an established inverse association between Se and chronic inflammation induced colon cancer (CICC), the mechanistic understanding of Se's protective effects requires additional in-vivo studies using preclinical animal models of CICC. Adiponectin (APN) is an adipocytokine that is protective against CICC as well. However, its role in the anti-mutagenic effects of the Se-diet remains unknown. To address this knowledge gap, here we examine the ability of dietary Se in reducing CICC in APN knockout mice (KO) and its wild-type C57BL/6. CICC was induced with the colon cancer agent 1,2 dimethyl hydrazine (DMH) along with dextran sodium sulfate (DSS). Se-enhanced diet increased selenoproteins, Gpx-1 and Gpx-2, in the colon tissues, thereby reducing oxidative stress. Se-mediated reduction of CICC was evident from the histopathological studies in both mouse models. In both mice, reduction in inflammation and tumorigenesis associated well with reduced p65 phosphorylation and elevated 53 phosphorylation. Finally, we show that in both models Se-administration promotes goblet cell differentiation with a concomitant increase in the levels of associated proteins, Muc-2 and Math-1. Our findings suggest that Se's protection against CICC involves both colonic epithelial protection and anti-tumor effects that are independent of APN.

The effect of rosmarinic acid on 1,2-dimethylhydrazine induced colon carcinogenesis.

PubMed

Venkatachalam, Karthikkumar; Gunasekaran, Sivagami; Jesudoss, Victor Antony Santiago; Namasivayam, Nalini

2013-05-01

This study was carried out to investigate the chemopreventive potential of rosmarinic acid (RA) against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the effect of RA on tumour formation, antioxidant enzymes, cytochrome P450 content, p-nitrophenol hydroxylase and GST activities. Rats were divided into six groups and fed modified pellet diet for the entire experimental period. Group 1 served as control, group 2 received RA (10 mg/kgb.w.). Groups 3-6 were induced colon cancer by injecting DMH (20 mg/kgb.w.) subcutaneously once a week for the first four weeks (groups 3-6). In addition, RA was administered at the doses of 2.5, 5 and 10 mg/kgb.w. to groups 4-6 respectively. DMH treated rats showed large number of colonic tumours; decreased lipid peroxidation; decreased antioxidant status; elevated CYP450 content and PNPH activities; and decreased GST activity in the liver and colon. Supplementation with RA (5 mgkg/b.w.) to DMH treated rats significantly decreased the number of polyps (50%); reversed the markers of oxidative stress (21.0%); antioxidant status (38.55%); CYP450 content (29.41%); and PNPH activities (21.9%). RA at the dose of 5 mg/kgb.w. showed a most pronounced effect and could be used as a possible chemopreventive agent against colon cancer. Copyright © 2011 Elsevier GmbH. All rights reserved.

Curcumin and docosahexaenoic acid block insulin-induced colon carcinoma cell proliferation.

PubMed

Fenton, Jenifer I; McCaskey, Sarah J

2013-03-01

Diets high in fish and curcumin are associated with a decreased risk of CRC. Insulin resistance and obesity are associated with increased CRC risk and higher reoccurrence rates. We utilized cell culture to determine if dietary compounds could reduce insulin-induced cell proliferation comparing the response in normal and metastatic colon epithelial cells. We treated model normal murine colon epithelial cells (YAMC) and adenocarcinoma cells (MC38) with docosahexaenoic acid (DHA) or curcumin alone and then co-treatments of the diet-derived compound and insulin were combined. Cell proliferation was stimulated with insulin (1 ug/mL) to model insulin resistance in obesity. Despite the presence of insulin, proliferation was reduced in the MC38 cells treated with 10 μM curcumin (p<0.001) and 50 μM DHA (p<0.001). Insulin stimulated MAPK and MEK phosphorylation was inhibited by DHA and curcumin in MC38 cancer cells. Here we show that curcumin and DHA can block insulin-induced colon cancer cell proliferation in vitro via a MEK mediated mechanism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Nasopharyngeal Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Nasopharyngeal cancer treatment options include radiation therapy, chemoradiation followed by adjuvant chemotherapy, surgery, and chemotherapy. Get detailed information about the treatment of newly diagnosed and recurrent nasopharyngeal cancer in this summary for clinicians.

A biomaterial-assisted mesenchymal stromal cell therapy alleviates colonic radiation-induced damage.

PubMed

Moussa, Lara; Pattappa, Girish; Doix, Bastien; Benselama, Sarra-Louiza; Demarquay, Christelle; Benderitter, Marc; Sémont, Alexandra; Tamarat, Radia; Guicheux, Jérôme; Weiss, Pierre; Réthoré, Gildas; Mathieu, Noëlle

2017-01-01

Healthy tissues surrounding abdomino-pelvic tumours can be impaired by radiotherapy, leading to chronic gastrointestinal complications with substantial mortality. Adipose-derived Mesenchymal Stromal Cells (Ad-MSCs) represent a promising strategy to reduce intestinal lesions. However, systemic administration of Ad-MSCs results in low cell engraftment within the injured tissue. Biomaterials, able to encapsulate and withstand Ad-MSCs, can overcome these limitations. A silanized hydroxypropylmethyl cellulose (Si-HPMC) hydrogel has been designed and characterized for injectable cell delivery using the operative catheter of a colonoscope. We demonstrated that hydrogel loaded-Ad-MSCs were viable, able to secrete trophic factors and responsive to the inflammatory environment. In a rat model of radiation-induced severe colonic damage, Ad-MSC + Si-HPMC improve colonic epithelial structure and hyperpermeability compared with Ad-MSCs injected intravenously or locally. This therapeutic benefit is associated with greater engraftment of Si-HPMC-embedded Ad-MSCs in the irradiated colonic mucosa. Moreover, macrophage infiltration near the injection site was less pronounced when Ad-MSCs were embedded in the hydrogel. Si-HPMC induces modulation of chemoattractant secretion by Ad-MSCs that could contribute to the decrease in macrophage infiltrate. Si-HPMC is suitable for cell delivery by colonoscopy and induces protection of Ad-MSCs in the tissue potentiating their therapeutic effect and could be proposed to patients suffering from colon diseases. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

CPT-11-Induced Delayed Diarrhea Develops via Reduced Aquaporin-3 Expression in the Colon

PubMed Central

Kon, Risako; Tsubota, Yuika; Minami, Moe; Kato, Saki; Matsunaga, Yukari; Kimura, Hiroshi; Murakami, Yuta; Fujikawa, Tetsuya; Sakurai, Ryoya; Tomimoto, Rei; Machida, Yoshiaki; Ikarashi, Nobutomo; Sugiyama, Kiyoshi

2018-01-01

While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed. The inflammation in the rat colon during diarrhea was caused via activated macrophage by CPT-11. These results showed that when CPT-11 is administered, the expression level of AQP3 in the colon is reduced, resulting in delayed diarrhea by preventing water transport from the intestinal tract. It was also suggested that the reduced expression of AQP3 might be due to the inflammation that occurs following the loss of colonic crypt cells and to the damage caused by the direct activation of macrophages by CPT-11. Therefore, it was considered that anti-inflammatory drugs that suppress the reduction of AQP3 expression could prevent CPT-11-induced delayed diarrhea. PMID:29316651

CPT-11-Induced Delayed Diarrhea Develops via Reduced Aquaporin-3 Expression in the Colon.

PubMed

Kon, Risako; Tsubota, Yuika; Minami, Moe; Kato, Saki; Matsunaga, Yukari; Kimura, Hiroshi; Murakami, Yuta; Fujikawa, Tetsuya; Sakurai, Ryoya; Tomimoto, Rei; Machida, Yoshiaki; Ikarashi, Nobutomo; Sugiyama, Kiyoshi

2018-01-06

While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed. The inflammation in the rat colon during diarrhea was caused via activated macrophage by CPT-11. These results showed that when CPT-11 is administered, the expression level of AQP3 in the colon is reduced, resulting in delayed diarrhea by preventing water transport from the intestinal tract. It was also suggested that the reduced expression of AQP3 might be due to the inflammation that occurs following the loss of colonic crypt cells and to the damage caused by the direct activation of macrophages by CPT-11. Therefore, it was considered that anti-inflammatory drugs that suppress the reduction of AQP3 expression could prevent CPT-11-induced delayed diarrhea.

Cytotoxicity of p-chloroamphetamine in dimethylhydrazine-induced carcinomata of rat colon.

PubMed

Tutton, P J; Barkla, D H

1979-01-01

Previous studies have shown that several serotonin-related compounds are cytotoxic to dimethylhydrazine-induced carcinomata of the colon of rat. This paper reports the cytotoxicity of another serotonin-related compound, p-chloroamphetamine.

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma.

PubMed

Ahmad, Munirah; Suhaimi, Shazlan-Noor; Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D S; Lo, Kwok-Wai; Ng, Chew-Hee; Khoo, Alan Soo-Beng

2018-01-01

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.

Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Wei-Xin, E-mail: weixinliu@yahoo.com; Wang, Ting; Zhou, Feng

Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentarymore » group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity. - Highlights: • Obesity down-regulates PPAR-γ in the colon. • Down-regulated colonic PPAR-γ may facilitate inflammatory

Childhood Nasopharyngeal Cancer Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood nasopharyngeal cancer treatment options include chemotherapy, external and internal radiation therapy, surgery, and immunotherapy (interferon). Learn more about the risk factors, symptoms, tests to diagnose, and treatment of childhood nasopharyngeal cancer in this expert-reviewed summary.

Coblation-assisted endonasal endoscopic resection of juvenile nasopharyngeal angiofibroma.

PubMed

Ye, L; Zhou, X; Li, J; Jin, J

2011-09-01

Juvenile nasopharyngeal angiofibroma may be successfully resected using endoscopic techniques. However, the use of coblation technology for such resection has not been described. This study aimed to document cases of Fisch class I juvenile nasopharyngeal angiofibroma with limited nasopharyngeal and nasal cavity extension, which were completely resected using an endoscopic coblation technique. We retrospectively studied 23 patients with juvenile nasopharyngeal angiofibroma who underwent resection with either traditional endoscopic instruments (n = 12) or coblation (n = 11). Intra-operative blood loss and overall operative time were recorded. The mean tumour resection time for coblation and traditional endoscopic instruments was 87 and 136 minutes, respectively (t = 9.962, p < 0.001). Mean intra-operative blood loss was 121 and 420 ml, respectively (t = 28.944, p < 0.001), a significant difference. Both techniques achieved complete tumour resection with minimal damage to adjacent tissues, and no recurrence in any patient. Coblation successfully achieves transnasal endoscopic resection of juvenile nasopharyngeal angiofibroma (Fisch class I), with good surgical margins and minimal blood loss.

[Effect of ginseng polysaccharide-induced wnt/beta-catenin signal transduction pathway on apoptosis of human nasopharyngeal cancer cells CNE-2].

PubMed

Fan, Jia-Ming; Liu, Ze-Hong; Li, Jing; Wang, Ya-Ping; Yang, Lv-Yuan; Huang, Jiang-Ju

2013-10-01

To observe the effect of ginseng polysaccharide (GPS) on the proliferation and apoptosis of human nasopharyngeal cancer cells CNE-2, and discuss the possible mechanism. The effect of GPS on the growth of CNE-2 cells was observed by CCK8 assay. CNE-2 cells in the logarithmic phase were collected and processed respectively with different concentrations (0, 0. 1, 0. 2, 0. 3. 0. 4 g L-1) of GPS for 48 h. The flow cytometry was used to detect its induction effect on CNE-2 cell apoptosis. Hoechst-33258 cell staining and electron microscope were used to observe the morphological changes of cells. The beta-catenin mRNA expression was detected by Real-time PCR. The protein localizations and expressions of beta-catenin and TCF4 were tested by the immunofluorescence staining. The expressions of beta-catenin, Bcl-2 and Bax proteins were detected by Western blot. CCK8 assay results showed that GPS could remarkably inhibit the proliferation of CNE-2 cells, with dose-time dependence. IC50 of cells induced with GPS for 48 h was 0. 39 g L-1. After being processed with GPS with concentrations of 0.1, 0. 2, 0. 3, 0. 4 g L-1 for 48 h, the cell apoptosis rates of human nasopharyngeal cancer cells CNE-2 were (5. 69 +/- 0. 29)% , (10. 3 +/- 0. 63)% , (15. 4 +/- 0. 74 ) % and (35. 7 +/- 1. 86)% , respectively. Significant difference was observed compared with the control group (2. 08 +/- 0. 11) % (P <0. 05). The results of Hoechst-33258 staining showed the characteristics of cell apoptosis. Under the electron microscope, apoptosis bodies could be observed among CNE-2 cells induced with GPS with the concentration of 0. 4 g L -1 for 48 h. The results of Real-time PCR showed a significant reduction in beta-catenin mRNA expression. The results of laser confocal microscopy revealed notable decrease of beta-catenin and TCF4 expression in nucleus and transfer from nucleus to cell membranes in beta-catenin expression areas after being processed with GPS for 48 h. Western blot showed significant

Mechanisms underlying 3-bromopyruvate-induced cell death in colon cancer.

PubMed

Sun, Yiming; Liu, Zhe; Zou, Xue; Lan, Yadong; Sun, Xiaojin; Wang, Xiu; Zhao, Surong; Jiang, Chenchen; Liu, Hao

2015-08-01

3-Bromopyruvate (3BP) is an energy-depleting drug that inhibits Hexokinase II activity by alkylation during glycolysis, thereby suppressing the production of ATP and inducing cell death. As such, 3BP can potentially serve as an anti-tumorigenic agent. Our previous research showed that 3BP can induce apoptosis via AKT /protein Kinase B signaling in breast cancer cells. Here we found that 3BP can also induce colon cancer cell death by necroptosis and apoptosis at the same time and concentration in the SW480 and HT29 cell lines; in the latter, autophagy was also found to be a mechanism of cell death. In HT29 cells, combined treatment with 3BP and the autophagy inhibitor 3-methyladenine (3-MA) exacerbated cell death, while viability in 3BP-treated cells was enhanced by concomitant treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk) and the necroptosis inhibitor necrostatin (Nec)-1. Moreover, 3BP inhibited tumor growth in a SW480 xenograft mouse model. These results indicate that 3BP can suppress tumor growth and induce cell death by multiple mechanisms at the same time and concentration in different types of colon cancer cell by depleting cellular energy stores.

Bilateral, independent juvenile nasopharyngeal angiofibroma: case report.

PubMed

Mørkenborg, M-L; Frendø, M; Stavngaard, T; Von Buchwald, C

2015-10-01

Juvenile nasopharyngeal angiofibroma is a benign, vascular tumour that primarily occurs in adolescent males. Despite its benign nature, aggressive growth patterns can cause potential life-threatening complications. Juvenile nasopharyngeal angiofibroma is normally unilateral, originating from the sphenopalatine artery, but bilateral symptoms can occur if a large tumour extends to the contralateral side of the nasopharynx. This paper presents the first reported case of true bilateral extensive juvenile nasopharyngeal angiofibroma involving clinically challenging pre-surgical planning and surgical strategy. A 21-year-old male presented with increasing bilateral nasal obstruction and discharge. Examination revealed tumours bilaterally and imaging demonstrated non-contiguous tumours. Pre-operative angiography showed strictly ipsilateral vascular supplies requiring bilateral embolisation. Radical removal performed as one-step, computer-assisted functional endoscopic sinus surgery was performed. The follow-up period was uncomplicated. This case illustrates the importance of suspecting bilateral juvenile nasopharyngeal angiofibroma in patients presenting with bilateral symptoms. Our management, including successful pre-operative planning, enabled one-step total removal of both tumours and rapid patient recovery.

Carbachol-induced colonic mucus formation requires transport via NKCC1, K+ channels and CFTR

PubMed Central

Lindén, Sara K.; Alwan, Ala H.; Scholte, Bob J.; Hansson, Gunnar C.; Sjövall, Henrik

2016-01-01

The colonic mucosa protects itself from the luminal content by secreting mucus that keeps the bacteria at a distance from the epithelium. For this barrier to be effective, the mucus has to be constantly replenished which involves exocytosis and expansion of the secreted mucins. Mechanisms involved in regulation of mucus exocytosis and expansion are poorly understood, and the aim of this study was to investigate whether epithelial anion secretion regulates mucus formation in the colon. The muscarinic agonist carbachol was used to induce parallel secretion of anions and mucus, and by using established inhibitors of ion transport, we studied how inhibition of epithelial transport affected mucus formation in mouse colon. Anion secretion and mucin exocytosis were measured by changes in membrane current and epithelial capacitance, respectively. Mucus thickness measurements were used to determine the carbachol effect on mucus growth. The results showed that the carbachol-induced increase in membrane current was dependent on NKCC1 co-transport, basolateral K+ channels and Cftr activity. In contrast, the carbachol-induced increase in capacitance was partially dependent on NKCC1 and K+ channel activity, but did not require Cftr activity. Carbachol also induced an increase in mucus thickness that was inhibited by the NKCC1 blocker bumetanide. However, mice that lacked a functional Cftr channel did not respond to carbachol with an increase in mucus thickness, suggesting that carbachol-induced mucin expansion requires Cftr channel activity. In conclusion, these findings suggest that colonic epithelial transport regulates mucus formation by affecting both exocytosis and expansion of the mucin molecules. PMID:25139191

Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

PubMed

Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

2016-09-01

Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage.

Grave's disease induced by radiotherapy for nasopharyngeal carcinoma: A case report and review of the literature.

PubMed

Ma, Jin-An; Li, Xuezhen; Zou, Wen; Zhou, Yan

2013-07-01

Radiotherapy is an effective treatment for nasopharyngeal carcinoma (NPC). A number of thyroid dysfunctions are induced by damage resulting from the relatively high doses of radiation administered to the thyroid and pituitary gland during radiotherapy. Hypothyroidism constitutes the most frequent type of thyroid dysfunction induced by NPC radiotherapy, while hyperthyroidism, particularly Grave's disease, is extremely rare. The present study describes the case of a 40-year-old male who presented with Grave's disease 2 years after receiving radiotherapy for the treatment of NPC. The patient exhibited swelling of the eyes, an increased appetite, decreased levels of thyroid-stimulating hormone, increased levels of triiodothyronine (T3) and thyroxine (T4) demonstrated by the examination of thyroid function and enlargement of the bilateral intraocular rectus revealed by CT scan. The patient's symptoms were ameliorated following treatment with propylthiouracil and propranolol for 1 month, and the levels of T3 and T4 were restored to normal. The pathophysiological mechanism of radiotherapy-induced hyperthyroidism has yet to be elucidated. Hyperthyroidism is often neglected as several of its clinical manifestations are similar to other complications observed during and following cancer treatment. Therefore, it is necessary to monitor thyroid function following head and neck radiotherapy.

Peptostreptococcus anaerobius Induces Intracellular Cholesterol Biosynthesis in Colon Cells to Induce Proliferation and Causes Dysplasia in Mice.

PubMed

Tsoi, Ho; Chu, Eagle S H; Zhang, Xiang; Sheng, Jianqiu; Nakatsu, Geicho; Ng, Siew C; Chan, Anthony W H; Chan, Francis K L; Sung, Joseph J Y; Yu, Jun

2017-05-01

Stool samples from patients with colorectal cancer (CRC) have a higher abundance of Peptostreptococcus anaerobius than stool from individuals without CRC, based on metagenome sequencing. We investigated whether P anaerobius contributes to colon tumor formation in mice and its possible mechanisms of carcinogenesis. We performed quantitative polymerase chain reaction analyses to measure P anaerobius in 112 stool samples and 255 colon biopsies from patients with CRC or advanced adenoma and from healthy individuals (controls) undergoing colonoscopy examination at hospitals in Hong Kong and Beijing. C57BL/6 mice were given broad-spectrum antibiotics, followed by a single dose of azoxymethane, to induce colon tumor formation. Three days later, mice were given P anaerobius or Esherichia coli MG1655 (control bacteria), via gavage, for 6 weeks. Some mice were also given the nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin. Intestine tissues were collected and analyzed histologically. The colon epithelial cell line NCM460 and colon cancer cell lines HT-29 and Caco-2 were exposed to P anaerobius or control bacteria; cells were analyzed by immunoblot, proliferation, and bacterial attachment analyses and compared in gene expression profiling studies. Gene expression was knocked down in these cell lines with small interfering RNAs. P anaerobius was significantly enriched in stool samples from patients with CRC and in biopsies from patients with colorectal adenoma or CRC compared with controls. Mice depleted of bacteria and exposed to azoxymethane and P anaerobius had a higher incidence of intestinal dysplasia (63%) compared with mice not given the bacteria (8.3%; P < .01). P anaerobius mainly colonized the colon compared with the rest of the intestine. Colon cells exposed to P anaerobius had significantly higher levels of proliferation than control cells. We found genes that regulate cholesterol biosynthesis, Toll-like receptor (TLR) signaling, and AMP

Gallic acid induced apoptotic events in HCT-15 colon cancer cells.

PubMed

Subramanian, Aruna Priyadharshni; Jaganathan, Saravana Kumar; Mandal, Mahitosh; Supriyanto, Eko; Muhamad, Ida Idayu

2016-04-21

To investigate the inhibitory action of diet-derived phenolic compound gallic acid (GA) against HCT-15 colon cancer cells. The antiproliferative effect of GA against colon cancer cells was determined by performing thiazolyl blue tetrazolium bromide (MTT) assay. The colony forming ability of GA treated colon cancer cells was evaluated using the colony forming assay. The cell cycle changes induced by GA in HCT-15 cells were analyzed by propidium iodide staining. Levels of reactive oxygen species (ROS) and mitochondrial membrane potential of HCT-15 exposed to GA was assessed using 2',7'-dichlorfluorescein-diacetate and rhodamine-123 respectively, with the help of flow cytometry. Morphological changes caused by GA treatment in the colon cancer cells were identified by scanning electron microscope and photomicrograph examination. Apoptosis was confirmed using flow cytometric analysis of GA treated HCT-15 cells after staining with Yo-Pro-1. MTT assay results illustrated that GA has an inhibitory effect on HCT-15 cells with IC50 value of 740 μmol/L. A time-dependent inhibition of colony formation was evident with GA treatment. Cell cycle arrest was evident from the accumulation of GA treated HCT-15 cells at sub-G1 phase (0.98 ± 1.03 vs 58.01 ± 2.05) with increasing exposure time. Flow cytometric analysis of GA treated HCT-15 cells depicted early events associated with apoptosis like lipid layer breakage and fall in mitochondrial membrane potential apart from an increase in the generation of ROS which were in a time dependent manner. SEM and photomicrograph images of the GA-treated cells displayed membrane blebbing and cell shrinking characteristics of apoptosis. Further apoptosis confirmation by Yo-Pro-1 staining also showed the time-dependent increase of apoptotic cells after treatment. These results show that GA induced ROS dependent apoptosis and inhibited the growth of colon cancer cells.

Cytomegalovirus-induced colonic stricture presenting as acute intestinal obstruction in an immunocompetent adult.

PubMed

Dinesh, B V; Selvaraju, Karthikeyan; Kumar, Sampath; Thota, Sumath

2013-09-10

Cytomegalovirus (CMV) infection causes significant morbidty and mortality in immunopromised patients. Though it is usually silent in immunocompetent adults, rarely it can cause serious life-threatening complications. Gastrointestinal tract is one of the commonly involved organs, where it produces a spectrum of clinical manifestation ranging from mild non-specific abdominal pain and diarrhoea to severe infection with toxic megacolon and death. We present a 65-year-old immunocompetent male patient admitted with acute colonic obstruction secondary to CMV-induced colonic stricture, highlighting the importance of considering it as a differential diagnosis for colonic obstruction and reviewing its management.

Chemopreventive effect of Cynodon dactylon (L.) Pers. extract against DMH-induced colon carcinogenesis in experimental animals.

PubMed

Albert-Baskar, Arul; Ignacimuthu, Savarimuthu

2010-07-01

The present study was aimed at evaluating the chemopreventive property of Cynodon dactylon. The antioxidant, antiproliferative and apoptotic potentials of the plant were investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, nitric oxide radical scavenging activity (NO(-)) and MTT assay on four cancer cell lines (COLO 320 DM, MCH-7, AGS, A549) and a normal cell line (VERO). In vivo chemopreventive property of the plant extract was studied in DMH-induced colon carcinogenesis. The methanolic extract of C. dactylon was found to be antiproliferative and antioxidative at lower concentrations and induced apoptotic cell death in COLO 320 DM cells. Treatment with methanolic extract of C. dactylon increased the levels of antioxidant enzymes and reduced the number of dysplastic crypts in DMH-induced colon of albino rats. The present investigation revealed the anticancer potential of methanolic extract of C. dactylon in COLO 320 DM cells and experimentally induced colon carcinogenesis in rats.

[6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling

PubMed Central

Narayanan, Sai Shyam; Nath, Lekshmi R.; Thulasidasan, Arun Kumar T.; Soniya, Eppurathu Vasudevan; Anto, Ruby John

2014-01-01

We report mechanism-based evidence for the anticancer and chemopreventive efficacy of [6]-gingerol, the major active principle of the medicinal plant, Ginger (Zingiber officinale), in colon cancer cells. The compound was evaluated in two human colon cancer cell lines for its cytotoxic effect and the most sensitive cell line, SW-480, was selected for the mechanistic evaluation of its anticancer and chemopreventive efficacy. The non-toxic nature of [6]-gingerol was confirmed by viability assays on rapidly dividing normal mouse colon cells. [6]-gingerol inhibited cell proliferation and induced apoptosis as evidenced by externalization of phosphatidyl serine in SW-480, while the normal colon cells were unaffected. Sensitivity to [6]-gingerol in SW-480 cells was associated with activation of caspases 8, 9, 3 &7 and cleavage of PARP, which attests induction of apoptotic cell death. Mechanistically, [6]-gingerol down-regulated Phorbol Myristate Acetate (PMA) induced phosphorylation of ERK1/2 and JNK MAP kinases and activation of AP-1 transcription factor, but had only little effects on phosphorylation of p38 MAP kinase and activation of NF-kappa B. Additionally, it complemented the inhibitors of either ERK1/2 or JNK MAP kinase in bringing down the PMA-induced cell proliferation in SW-480 cells. We report the inhibition of ERK1/2/JNK/AP-1 pathway as a possible mechanism behind the anticancer as well as chemopreventive efficacy of [6]-gingerol against colon cancer. PMID:25157570

[6]-Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling.

PubMed

Radhakrishnan, E K; Bava, Smitha V; Narayanan, Sai Shyam; Nath, Lekshmi R; Thulasidasan, Arun Kumar T; Soniya, Eppurathu Vasudevan; Anto, Ruby John

2014-01-01

We report mechanism-based evidence for the anticancer and chemopreventive efficacy of [6]-gingerol, the major active principle of the medicinal plant, Ginger (Zingiber officinale), in colon cancer cells. The compound was evaluated in two human colon cancer cell lines for its cytotoxic effect and the most sensitive cell line, SW-480, was selected for the mechanistic evaluation of its anticancer and chemopreventive efficacy. The non-toxic nature of [6]-gingerol was confirmed by viability assays on rapidly dividing normal mouse colon cells. [6]-gingerol inhibited cell proliferation and induced apoptosis as evidenced by externalization of phosphatidyl serine in SW-480, while the normal colon cells were unaffected. Sensitivity to [6]-gingerol in SW-480 cells was associated with activation of caspases 8, 9, 3 &7 and cleavage of PARP, which attests induction of apoptotic cell death. Mechanistically, [6]-gingerol down-regulated Phorbol Myristate Acetate (PMA) induced phosphorylation of ERK1/2 and JNK MAP kinases and activation of AP-1 transcription factor, but had only little effects on phosphorylation of p38 MAP kinase and activation of NF-kappa B. Additionally, it complemented the inhibitors of either ERK1/2 or JNK MAP kinase in bringing down the PMA-induced cell proliferation in SW-480 cells. We report the inhibition of ERK1/2/JNK/AP-1 pathway as a possible mechanism behind the anticancer as well as chemopreventive efficacy of [6]-gingerol against colon cancer.

Nasopharyngeal Case-Control Study

Cancer.gov

A case-control study conducted in Taiwan between 1991-1994 among approximately 1,000 individuals to examine the role of viral, environmental, and genetic factors associated with the development of nasopharyngeal carcinoma

Nasopharyngeal teratoma as a cause of neonatal stridor.

PubMed

Tiwari, Lokesh; Baijal, Noopur; Puliyel, Jacob M

2009-12-01

We report nasopharyngeal teratoma in a term female neonate, that presented within first week of life with episodic stridor, apnea and cyanosis. Laryngoscopy revealed a mass which was confirmed by MRI. The mass was surgically excised and diagnosed as nasopharyngeal teratoma on histopathology. The child is doing well on follow-up.

Reassessing the Anatomic Origin of the Juvenile Nasopharyngeal Angiofibroma.

PubMed

McKnight, Colin D; Parmar, Hemant A; Watcharotone, Kuanwong; Mukherji, Suresh K

A modern imaging review is necessary to further define the anatomic origin of the juvenile nasopharyngeal angiofibroma. After institutional review board approval, a search from January 1998 to January 2013 yielded 33 male patients (aged 10-23 years) with pathologically proven juvenile nasopharyngeal angiofibroma lesions, as well as pretreatment computed tomography/magnetic resonance imaging. Juvenile nasopharyngeal angiofibroma involvement was assessed in the following regions: sphenopalatine foramen, pterygopalatine fossa, vidian canal, nasopharynx, nasal cavity, sphenoid sinus, choana, pterygomaxillary fissure/masticator space, orbit, and sphenoid bone. The choana and nasopharynx were involved in all 33 patients. In contrast, only 22 lesions involved the pterygopalatine fossa, 24 lesions involved the sphenopalatine foramen, and 28 lesions involved the vidian canal. Our results suggest that the juvenile nasopharyngeal angiofibroma origin is in the region of the choana and nasopharynx rather than the sphenopalatine foramen or pterygopalatine fossa.

Ischemic or toxic injury: A challenging diagnosis and treatment of drug-induced stenosis of the sigmoid colon.

PubMed

Zhang, Zong-Ming; Lin, Xiang-Chun; Ma, Li; Jin, An-Qin; Lin, Fang-Cai; Liu, Zhuo; Liu, Li-Min; Zhang, Chong; Zhang, Na; Huo, Li-Juan; Jiang, Xue-Liang; Kang, Feng; Qin, Hong-Jun; Li, Qiu-Yang; Yu, Hong-Wei; Deng, Hai; Zhu, Ming-Wen; Liu, Zi-Xu; Wan, Bai-Jiang; Yang, Hai-Yan; Liao, Jia-Hong; Luo, Xu; Li, You-Wei; Wei, Wen-Ping; Song, Meng-Meng; Zhao, Yue; Shi, Xue-Ying; Lu, Zhao-Hui

2017-06-07

A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.

Carbachol-induced colonic mucus formation requires transport via NKCC1, K⁺ channels and CFTR.

PubMed

Gustafsson, Jenny K; Lindén, Sara K; Alwan, Ala H; Scholte, Bob J; Hansson, Gunnar C; Sjövall, Henrik

2015-07-01

The colonic mucosa protects itself from the luminal content by secreting mucus that keeps the bacteria at a distance from the epithelium. For this barrier to be effective, the mucus has to be constantly replenished which involves exocytosis and expansion of the secreted mucins. Mechanisms involved in regulation of mucus exocytosis and expansion are poorly understood, and the aim of this study was to investigate whether epithelial anion secretion regulates mucus formation in the colon. The muscarinic agonist carbachol was used to induce parallel secretion of anions and mucus, and by using established inhibitors of ion transport, we studied how inhibition of epithelial transport affected mucus formation in mouse colon. Anion secretion and mucin exocytosis were measured by changes in membrane current and epithelial capacitance, respectively. Mucus thickness measurements were used to determine the carbachol effect on mucus growth. The results showed that the carbachol-induced increase in membrane current was dependent on NKCC1 co-transport, basolateral K(+) channels and Cftr activity. In contrast, the carbachol-induced increase in capacitance was partially dependent on NKCC1 and K(+) channel activity, but did not require Cftr activity. Carbachol also induced an increase in mucus thickness that was inhibited by the NKCC1 blocker bumetanide. However, mice that lacked a functional Cftr channel did not respond to carbachol with an increase in mucus thickness, suggesting that carbachol-induced mucin expansion requires Cftr channel activity. In conclusion, these findings suggest that colonic epithelial transport regulates mucus formation by affecting both exocytosis and expansion of the mucin molecules.

Synchronous parotid and nasopharyngeal Warthin tumor.

PubMed

Ory, Madgar; Eran, Alon

2016-03-01

Warthin tumor is the second most common benign salivary gland neoplasm after pleomorphic adenoma. Warthin tumors occur almost exclusively in the parotid gland and periparotid lymph nodes, extraparotid localization is rare. We describe a case of a patient presenting with a synchronous unilateral parotid gland and nasopharyngeal Warthin tumor. We propose that, although this occurrence of a synchronous parotid gland and nasopharyngeal Warthin tumor may be coincidental, it is more likely to be an effect of a systemic factor. © 2015 Wiley Periodicals, Inc.

The role of substance P in the maintenance of colonic hypermotility induced by repeated stress in rats.

PubMed

Lu, Ping; Luo, Hesheng; Quan, Xiaojing; Fan, Han; Tang, Qincai; Yu, Guang; Chen, Wei; Xia, Hong

2016-04-01

The mechanism underlying chronic stress-induced gastrointestinal (GI) dysmotility has not been fully elucidated and GI hormones have been indicated playing a role in mediating stress-induced changes in GI motor function. Our objective was to study the possible role of substance P (SP) in the colonic hypermotility induced by repeated water avoidance stress (WAS) which mimics irritable bowel syndrome. Male Wistar rats were submitted to WAS or sham WAS (SWAS) (1h/day) for up to 10 consecutive days. Enzyme Immunoassay Kit was used to detect the serum level of SP. The expression of neurokinin-1 receptor (NK1R) was investigated by Immunohistochemistry and Western blotting. The spontaneous contraction of muscle strip was studied in an organ bath system. L-type calcium channel currents (ICa,L) of smooth muscle cells (SMCs) were recorded by whole-cell patch-clamp technique. Fecal pellet expulsion and spontaneous contraction of proximal colon in rats were increased after repeated WAS. The serum level of SP was elevated following WAS. Immunohistochemistry proved the expression of NK1R in mucosa, muscularis and myenteric plexus. Western blotting demonstrated stress-induced up-regulation of NK1R in colon devoid of mucosa and submucosa. Repeated WAS increased the contractile activities of longitudinal muscle and circular muscle strips induced by SP and this effect was reversed by a selective NK1R antagonist. The ICa,L of SMCs in the WAS rats were drastically increased compared to controls after addition of SP. Increased serum SP level and up-regulated NK1R in colon may contribute to stress-induced colonic hypermotility. And L-type calcium channels play a potentially important role in the process of WAS-induced dysmotility. Copyright © 2016 Elsevier Ltd. All rights reserved.

Primary and secondary hypothyroidism in nasopharyngeal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, M.B.; Goldfine, I.D.

1976-10-04

We investigated the thyroid and pituitary functions of six of the seven patients with nasopharyngeal carcinoma who had been previously treated with external radiation, and who were seen at the San Francisco Veterans Administration Hospital within a recent 18-month period. Two patients had primary hypothyroidism, and four had secondary hypothyroidism. These findings suggest that thyroid and pituitary abnormalities are frequent complications of both nasopharyngeal carcinoma and its treatment.

Grave’s disease induced by radiotherapy for nasopharyngeal carcinoma: A case report and review of the literature

PubMed Central

MA, JIN-AN; LI, XUEZHEN; ZOU, WEN; ZHOU, YAN

2013-01-01

Radiotherapy is an effective treatment for nasopharyngeal carcinoma (NPC). A number of thyroid dysfunctions are induced by damage resulting from the relatively high doses of radiation administered to the thyroid and pituitary gland during radiotherapy. Hypothyroidism constitutes the most frequent type of thyroid dysfunction induced by NPC radiotherapy, while hyperthyroidism, particularly Grave’s disease, is extremely rare. The present study describes the case of a 40-year-old male who presented with Grave’s disease 2 years after receiving radiotherapy for the treatment of NPC. The patient exhibited swelling of the eyes, an increased appetite, decreased levels of thyroid-stimulating hormone, increased levels of triiodothyronine (T3) and thyroxine (T4) demonstrated by the examination of thyroid function and enlargement of the bilateral intraocular rectus revealed by CT scan. The patient’s symptoms were ameliorated following treatment with propylthiouracil and propranolol for 1 month, and the levels of T3 and T4 were restored to normal. The pathophysiological mechanism of radiotherapy-induced hyperthyroidism has yet to be elucidated. Hyperthyroidism is often neglected as several of its clinical manifestations are similar to other complications observed during and following cancer treatment. Therefore, it is necessary to monitor thyroid function following head and neck radiotherapy. PMID:23946792

Olfactory Training in Improving Sense of Smell After Radiation Therapy in Patients With Paranasal Sinus or Nasopharyngeal Cancer

ClinicalTrials.gov

2017-07-11

Stage 0 Nasopharyngeal Carcinoma; Stage 0 Paranasal Sinus Cancer; Stage I Nasopharyngeal Carcinoma; Stage I Paranasal Sinus Cancer; Stage II Nasopharyngeal Carcinoma; Stage II Paranasal Sinus Cancer; Stage IIA Nasopharyngeal Carcinoma; Stage IIB Nasopharyngeal Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage III Paranasal Sinus Cancer; Stage IV Nasopharyngeal Carcinoma; Stage IV Paranasal Sinus Cancer; Stage IVA Nasopharyngeal Carcinoma; Stage IVA Paranasal Sinus Cancer; Stage IVB Nasopharyngeal Carcinoma; Stage IVB Paranasal Sinus Cancer; Stage IVC Nasopharyngeal Carcinoma; Stage IVC Paranasal Sinus Cancer

Juvenile nasopharyngeal angiofibroma: Timisoara ENT Department's experience.

PubMed

Iovanescu, Gheorghe; Ruja, Steluta; Cotulbea, Stan

2013-07-01

Juvenile nasopharyngeal angiofibroma is a histologically benign, but very aggressive and destructive tumor found exclusively in young males. The management of juvenile nasopharyngeal angiofibroma has changed in recent years, but it still continues to be a challenge for the multidisciplinary head and neck surgical team. The purpose of this study was to review a series of 30 patients describing the treatment approach used and studying the outcome of juvenile nasopharyngeal angiofibroma in the ENT Department Timisoara, Romania for a period of 30 years. The patients were diagnosed and treated during the years 1981-2011. All patients were male. Tumors were classified using Radkowski's staging system. Computed tomography and magnetic resonance imaging allowed for accurate diagnosis and staging of the tumors. Biopsies were not performed. Surgery represented the gold standard for treatment of juvenine nasopharyngeal angiofibroma. All patients had the tumor removed by an external approach, endoscopic surgical approach not being employed in this series of patients. All patients were treated surgically. Surgical techniques performed were: Denker-Rouge technique in 13 cases (43.33%), paralateronasal technique in 7 cases (23.33%), retropalatine technique in 5 cases (16.66%) and transpalatine technique in 5 cases (16.66%). No preoperative tumor embolization was performed. The recurrence rate was 16.66%. The follow-up period ranged from 1 year to 12 years. Management of juvenile nasopharyngeal angiofibroma remains a surgical challenge. Clinical evaluation and surgical experience are very important in selecting the proper approach. A multidisciplinary team, with an experienced surgeon and good collaboration with the anesthesiologist are needed for successful surgical treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Study on nasopharyngeal cancer tissue using surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ge, Xiaosong; Lin, Xueliang; Xu, Zhihong; Wei, Guoqiang; Huang, Wei; Lin, Duo

2016-10-01

Surface-enhanced Raman spectroscopy (SERS) can provide detailed molecular structure and composition information, and has demonstrated great potential in biomedical filed. This spectroscopy technology has become one of the most important optical techniques in the early diagnosis of cancer. Nasopharyngeal cancer (NPC) is a malignant neoplasm arising in the nasopharyngeal epithelial lining, which has relatively high incidence and death rate in Southeast Asia and southern China. This paper reviews the current progress of SERS in the field of cancer diagnostics, including gastric cancer, colorectal cancer, cervical cancer and nasopharyngeal cancer. In addition to above researches, we recently develop a novel NPC detection method based on tissue section using SERS, and obtain primary results. The proposed method has promising potential for the detection of nasopharyngeal carcinoma.

Paraneoplastic Neurological Disorder in Nasopharyngeal Carcinoma.

PubMed

Ng, Sze Yin; Kongg, Min Han; Yunus, Mohd Razif Mohamad

2017-03-01

Paraneoplastic neurological disorder (PND) is a condition due to immune cross-reactivity between the tumour cells and the normal tissue, whereby the "onconeural" antibodies attack the normal host nervous system. It can present within weeks to months before or after the diagnosis of malignancies. Nasopharyngeal carcinoma is associated with paraneoplastic syndrome, for example, dermatomyositis, and rarely with a neurological disorder. We report on a case of nasopharyngeal carcinoma with probable PND. Otolaryngologists, oncologists and neurologists need to be aware of this condition in order to make an accurate diagnosis and to provide prompt treatment.

Curcumin derivative WZ35 efficiently suppresses colon cancer progression through inducing ROS production and ER stress-dependent apoptosis.

PubMed

Zhang, Junru; Feng, Zhiguo; Wang, Chunhua; Zhou, Huiping; Liu, Weidong; Kanchana, Karvannan; Dai, Xuanxuan; Zou, Peng; Gu, Junlian; Cai, Lu; Liang, Guang

2017-01-01

Colon cancer is characterized by its fast progression and poor prognosis, and novel agents of treating colon cancer are urgently needed. WZ35, a synthetic curcumin derivative, has been reported to exhibit promising antitumor activity. Here, we investigated the in vitro and in vivo activities of WZ35 and explored the underlying mechanisms in colon cancer cell lines. WZ35 treatment significantly decreased the cell viability associated with G2/M cell cycle arrest and apoptosis induction in colon cancer cell lines. We also show that WZ35 is highly effective in inhibiting tumor growth in a CT26 xenograft mouse model. Mechanistically, WZ35 treatment significantly induced reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress in CT26 cells. Abrogation of ROS production by N-acetylcysteine (NAC) co-treatment almost totally reversed the WZ35-induced cell apoptosis and ER stress activation. Inhibition of p-PERK by GSK2606414 can significantly reverse WZ35-induced cell apoptosis in CT26 cells. Taken together, the curcumin derivative WZ35 exhibited anti-tumor effects in colon cancer cells both in vitro and in vivo, via a ROS-ER stress-mediated mechanism. These findings indicate that activating ROS generation could be an important strategy for the treatment of colon cancers.

Hypothalamic beta-endorphin neurons suppress preneoplastic and neoplastic lesions development in 1,2-dimethylhydrazine induced rat colon cancer model.

PubMed

Murugan, Sengottuvelan; Dave, Yatee; Rakhit, Ankush; Sarkar, Dipak K

2017-01-01

In recent years, experimental studies demonstrated negative impacts of impaired body stress response on colonic pathologies. In this study, we tested if reducing body stress response by the use of β-endorphin (BEP) neuronal transplants in the hypothalamus suppresses pre-neoplastic and neoplastic lesions. Colon cancer was induced by injecting 1,2-dimethylhydrazine (DMH) for sixteen weeks in Sprague Dawley rats with BEP neuron transplants or control neuron transplants, and their colonic histopathologies, colon tissue levels of pro-inflammatory cytokines and epithelial-mesenchymal transition (EMT) proteins and splenic levels of cytotoxic proteins were measured. Our results revealed that DMH induced tumors in colon at 100% incidence in control rats but failed to induce colonic tumors in 70% of animal with BEP neuronal transplants. The mean volume of tumor at the colon was smaller in BEP neurons transplanted rats than those in controls. Histopathologies of colon tissues revealed that BEP neurons transplanted animals had lesser tissue lesions such as aberrant crypt foci (ACF) and adenocarcinoma development in the colon than those in control groups. Immunohistochemical and western blot analyses identified reduced expression of Ki-67, TNF-α and NF-κB nuclear translocation in colonic tissues of BEP neurons transplanted rats than those in controls. BEP neurons transplanted rats also showed reduced expressions of transcription factors linked to EMT like Snail, Twist, and N-cadherin, but increased the levels of an epithelial cell marker E-cadherin in colon tissue. Furthermore, splenic NK cells cytolytic proteins such as perforin, granzyme B and IFN-γ levels in BEP neurons transplanted rats were higher than those in control rats. These data suggest that BEP neuron transplants suppress the growth and progression of colonic tumors possibly by decreasing inflammatory mileu and EMT via activation of innate immune responses.

Emodin induces chloride secretion in rat distal colon through activation of mast cells and enteric neurons

PubMed Central

Xu, J-D; Liu, S; Wang, W; Li, L-S; Li, X-F; Li, Y; Guo, H; Ji, T; Feng, X-Y; Hou, X-L; Zhang, Y; Zhu, J-X

2012-01-01

BACKGROUND AND PURPOSE Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active component of many herb-based laxatives. However, its mechanism of action is unclear. The aim of the present study was to investigate the role of mast cells and enteric neurons in emodin-induced ion secretion in the rat colon. EXPERIMENTAL APPROACH Short-circuit current (ISC) recording was used to measure epithelial ion transport. A scanning ion-selective electrode technique was used to directly measure Cl- flux (JCl−) across the epithelium. RIA was used to measure emodin-induced histamine release. KEY RESULTS Basolateral addition of emodin induced a concentration-dependent increase in ISC in colonic mucosa/submucosa preparations, EC50 75 µM. The effect of emodin was blocked by apically applied glibenclamide, a Cl- channel blocker, and by basolateral application of bumetanide, an inhibitor of the Na+-K+-2Cl- cotransporter. Emodin-evoked JCl− in mucosa/submucosa preparations was measured by scanning ion-selective electrode technique, which correlated to the increase in ISC and was significantly suppressed by glibenclamide and bumetanide. Pretreatment with tetrodotoxin and the muscarinic receptor antagonist atropine had no effect on emodin-induced ΔISC in mucosa-only preparations, but significantly reduced emodin-induced ΔISC and JCl− in mucosa/submucosa preparations. The COX inhibitor indomethacin, the mast cell stabilizer ketotifen and H1 receptor antagonist pyrilamine significantly reduced emodin-induced ΔISC in mucosa and mucosa/submucosa preparations. The H2 receptor antagonist cimetidine inhibited emodin-induced ΔISC and JCl− only in the mucosa/submucosa preparations. Furthermore, emodin increased histamine release from the colonic mucosa/submucosa tissues. CONCLUSIONS AND IMPLICATIONS The results suggest that emodin-induced colonic Cl- secretion involves mast cell degranulation and activation of cholinergic and non-cholinergic submucosal neurons. PMID:21718311

Western diet induces colonic nitrergic myenteric neuropathy and dysmotility in mice via saturated fatty acid- and lipopolysaccharide-induced TLR4 signalling.

PubMed

Reichardt, François; Chassaing, Benoit; Nezami, Behtash Ghazi; Li, Ge; Tabatabavakili, Sahar; Mwangi, Simon; Uppal, Karan; Liang, Bill; Vijay-Kumar, Matam; Jones, Dean; Gewirtz, Andrew T; Srinivasan, Shanthi

2017-03-01

A high-fat diet (60% kcal from fat) is associated with motility disorders inducing constipation and loss of nitrergic myenteric neurons in the proximal colon. Gut microbiota dysbiosis, which occurs in response to HFD, contributes to endotoxaemia. High levels of lipopolysaccharide lead to apoptosis in cultured myenteric neurons that express Toll-like receptor 4 (TLR4). Consumption of a Western diet (WD) (35% kcal from fat) for 6 weeks leads to gut microbiota dysbiosis associated with altered bacterial metabolites and increased levels of plasma free fatty acids. These disorders precede the nitrergic myenteric cell loss observed in the proximal colon. Mice lacking TLR4 did not exhibit WD-induced myenteric cell loss and dysmotility. Lipopolysaccharide-induced in vitro enteric neurodegeneration requires the presence of palmitate and may be a result of enhanced NO production. The present study highlights the critical role of plasma saturated free fatty acids that are abundant in the WD with respect to driving enteric neuropathy and colonic dysmotility. The consumption of a high-fat diet (HFD) is associated with myenteric neurodegeneration, which in turn is associated with delayed colonic transit and constipation. We examined the hypothesis that an inherent increase in plasma free fatty acids (FFA) in the HFD together with an HFD-induced alteration in gut microbiota contributes to the pathophysiology of these disorders. C57BL/6 mice were fed a Western diet (WD) (35% kcal from fat enriched in palmitate) or a purified regular diet (16.9% kcal from fat) for 3, 6, 9 and 12 weeks. Gut microbiota dysbiosis was investigated by fecal lipopolysaccharide (LPS) measurement and metabolomics (linear trap quadrupole-Fourier transform mass spectrometer) analysis. Plasma FFA and LPS levels were assessed, in addition to colonic and ileal nitrergic myenteric neuron quantifications and motility. Compared to regular diet-fed control mice, WD-fed mice gained significantly more weight

The influence of androgens, anti-androgens, and castration on cell proliferation in the jejunal and colonic crypt epithelia, and in dimethylhydrazine-induced adenocarcinoma of rat colon.

PubMed

Tutton, P J; Barkla, D H

1982-01-01

Androgenic hormones have previously been shown to promote cell proliferation in the small intestine of rat and androgen receptors have been demonstrated in carcinomata of the large intestine of rat. In this study the influence of testosterone and of castration on epithelial cell proliferation in the small intestine, the large intestine and in dimethylhydrazine-induced colonic tumours is compared. Cell proliferation in the small intestine and in colonic tumours was accelerated by testosterone treatment, and cell proliferation in colonic tumours, but not in the small intestine, was retarded following castration. Cell proliferation in colonic tumours was also inhibited by the anti-androgenic drug, Flutamide. Testosterone and castration each failed to influence cell proliferation in the colonic crypt epithelium of both normal and carcinogen-treated animals.

Gallic acid induced apoptotic events in HCT-15 colon cancer cells

PubMed Central

Subramanian, Aruna Priyadharshni; Jaganathan, Saravana Kumar; Mandal, Mahitosh; Supriyanto, Eko; Muhamad, Ida Idayu

2016-01-01

AIM: To investigate the inhibitory action of diet-derived phenolic compound gallic acid (GA) against HCT-15 colon cancer cells. METHODS: The antiproliferative effect of GA against colon cancer cells was determined by performing thiazolyl blue tetrazolium bromide (MTT) assay. The colony forming ability of GA treated colon cancer cells was evaluated using the colony forming assay. The cell cycle changes induced by GA in HCT-15 cells were analyzed by propidium iodide staining. Levels of reactive oxygen species (ROS) and mitochondrial membrane potential of HCT-15 exposed to GA was assessed using 2’,7’-dichlorfluorescein-diacetate and rhodamine-123 respectively, with the help of flow cytometry. Morphological changes caused by GA treatment in the colon cancer cells were identified by scanning electron microscope and photomicrograph examination. Apoptosis was confirmed using flow cytometric analysis of GA treated HCT-15 cells after staining with Yo-Pro-1. RESULTS: MTT assay results illustrated that GA has an inhibitory effect on HCT-15 cells with IC50 value of 740 μmol/L. A time-dependent inhibition of colony formation was evident with GA treatment. Cell cycle arrest was evident from the accumulation of GA treated HCT-15 cells at sub-G1 phase (0.98 ± 1.03 vs 58.01 ± 2.05) with increasing exposure time. Flow cytometric analysis of GA treated HCT-15 cells depicted early events associated with apoptosis like lipid layer breakage and fall in mitochondrial membrane potential apart from an increase in the generation of ROS which were in a time dependent manner. SEM and photomicrograph images of the GA-treated cells displayed membrane blebbing and cell shrinking characteristics of apoptosis. Further apoptosis confirmation by Yo-Pro-1 staining also showed the time-dependent increase of apoptotic cells after treatment. CONCLUSION: These results show that GA induced ROS dependent apoptosis and inhibited the growth of colon cancer cells. PMID:27099438

Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan

2012-05-11

Highlights: Black-Right-Pointing-Pointer Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. Black-Right-Pointing-Pointer G{sub 2}/M phase arrest and chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Noscapine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colonmore » cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC{sub 50} = 75 {mu}M). This cytotoxicity was reflected by cell cycle arrest at G{sub 2}/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.« less

Ischemic or toxic injury: A challenging diagnosis and treatment of drug-induced stenosis of the sigmoid colon

PubMed Central

Zhang, Zong-Ming; Lin, Xiang-Chun; Ma, Li; Jin, An-Qin; Lin, Fang-Cai; Liu, Zhuo; Liu, Li-Min; Zhang, Chong; Zhang, Na; Huo, Li-Juan; Jiang, Xue-Liang; Kang, Feng; Qin, Hong-Jun; Li, Qiu-Yang; Yu, Hong-Wei; Deng, Hai; Zhu, Ming-Wen; Liu, Zi-Xu; Wan, Bai-Jiang; Yang, Hai-Yan; Liao, Jia-Hong; Luo, Xu; Li, You-Wei; Wei, Wen-Ping; Song, Meng-Meng; Zhao, Yue; Shi, Xue-Ying; Lu, Zhao-Hui

2017-01-01

A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids. PMID:28638234

An Ahemolytic Pneumolysin of Streptococcus Pneumoniae Manipulates Human Innate and CD4+ T-Cell Responses and Reduces Resistance to Colonization in Mice in a Serotype-Independent Manner

PubMed Central

Khan, M. Nadeem; Coleman, John Robert; Vernatter, Joshua; Varshney, Avanish Kumar; Dufaud, Chad; Pirofski, Liise-anne

2014-01-01

Background. Some Streptococcus pneumoniae serotypes express an ahemolytic pneumolysin (PLYa). Serotypes that commonly express PLYa, including serotype 8 (ST8) and ST1, are often associated with a low prevalence during colonization but a higher propensity to cause invasive disease. We sought to study the host response to ST8 PLYa in a homologous and heterologous capsular background. Methods. We genetically exchanged the PLYa of ST8 strain 6308 with the hemolytic PLY (PLYh) of ST3 A66.1 and vice versa and determined the impact of the exchange on nasopharyngeal colonization in mice. Then, to compare the response of human cells to PLYa-expressing and PLYh-expressing strains, we infected human peripheral blood mononuclear cells (PBMCs) with PLY-switched strains and assessed dendritic cell and CD4+ T-cell responses by intracellular cytokine staining. Result. Mice colonized with PLYa-expressing strains had significantly higher colonization densities than those colonized with PLYh-expressing strains, irrespective of capsular background. Compared with infection of PBMCs with PLYh-expressing strains, infection with PLYa-expressing strains induced diminished innate (dendritic cell cytokines, costimulatory receptor, and apoptotic) and adaptive (CD4+ T-cell proliferative and memory interleukin 17A) responses. Conclusion. Our findings demonstrate that PLYa has the potential to manipulate host immunity irrespective of capsule type. PLY exchange between STs expressing PLYa and PLYh could lead to unexpected colonization or invasion phenotypes. PMID:25001458

Cryptococcal nasopharyngeal polypoid mass in a cat

PubMed Central

Javard, Romain; Alexander, Kate; Girard, Christiane; Dunn, Marilyn

2015-01-01

Case summary An indoor 9-year-old castrated male domestic cat was referred with a 4 month history of increased upper airway noise. Computed tomography revealed a nasopharyngeal polypoid mass, which was removed endoscopically with basket forceps. Histopathology was compatible with a polypoid granulomatous pharyngitis with Cryptococcus-like organisms. This was supported by a positive serum latex cryptococcal antigen agglutination test (LCAT). Minimal inflammation of the nasal tissue was noted on histopathology, with no evidence of fungus. Following endoscopic removal of the mass, the patient was treated with systemic antifungal medication (itraconazole). One year after diagnosis, the LCAT titer was negative and the cat remained free of clinical signs. Relevance and novel information This case report emphasizes the importance of considering Cryptococcus species as a potential etiology in cats presented with signs of nasopharyngeal obstruction with an isolated nasopharyngeal polypoid mass, even if kept indoors. PMID:28491377

Nasopharyngeal bacterial burden and antibiotics: Influence on inflammatory markers and disease severity in infants with respiratory syncytial virus bronchiolitis.

PubMed

Suárez-Arrabal, M Carmen; Mella, Cesar; Lopez, Santiago M; Brown, Nicole V; Hall, Mark W; Hammond, Sue; Shiels, William; Groner, Judith; Marcon, Mario; Ramilo, Octavio; Mejias, Asuncion

2015-10-01

Animal studies suggest that RSV increases nasopharyngeal (NP) bacterial colonization facilitating bacterial infections. We investigated the influence of antibiotic treatment and colonization with potentially pathogenic bacteria on inflammatory markers and disease severity in RSV-infected in infants. Healthy young infants hospitalized with RSV bronchiolitis (n = 136) and age-matched healthy controls (n = 23) were enrolled and NP samples cultured for potentially pathogenic bacteria including: Gram-positive bacteria (GPB): Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic Streptococcus; and Gram-negative bacteria (GNB): Moraxella catarrhalis and Haemophilus influenzae. Clinical parameters and plasma IL-8, IL-6 and TNF-α concentrations were compared according to the bacterial class and antibiotic treatment. Antibiotic treatment decreased by 10-fold NP bacterial recovery. Eighty-one percent of RSV infants who did not receive antibiotics before sample collection were colonized with pathogenic bacteria. Overall, GNB were identified in 21% of patients versus 4% of controls who were mostly colonized with GPB. Additionally, in RSV patients NP white blood cell counts (p = 0.026), and blood neutrophils (p = 0.02) were higher in those colonized with potentially pathogenic bacteria versus respiratory flora. RSV patients colonized with GNB had higher plasma IL-8 (p = 0.01) and IL-6 (p < 0.01) concentrations than controls, and required longer duration of oxygen (p = 0.049). Infants with RSV bronchiolitis colonized with potentially pathogenic bacteria had increased numbers of mucosal and systemic inflammatory cells. Specifically, colonization with GNB was associated with higher concentrations of proinflammatory cytokines and a trend towards increased disease severity. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Fungal colonization of an Ordovician impact-induced hydrothermal system

PubMed Central

Ivarsson, Magnus; Broman, Curt; Sturkell, Erik; Ormö, Jens; Siljeström, Sandra; van Zuilen, Mark; Bengtson, Stefan

2013-01-01

Impacts are common geologic features on the terrestrial planets throughout the solar system, and on at least Earth and Mars impacts have induced hydrothermal convection. Impact-generated hydrothermal systems have been suggested to possess the same life supporting capability as hydrothermal systems associated with volcanic activity. However, evidence of fossil microbial colonization in impact-generated hydrothermal systems is scarce in the literature. Here we report of fossilized microorganisms in association with cavity-grown hydrothermal minerals from the 458 Ma Lockne impact structure, Sweden. Based on morphological characteristics the fossilized microorganisms are interpreted as fungi. We further infer the kerogenization of the microfossils, and thus the life span of the fungi, to be contemporaneous with the hydrothermal activity and migration of hydrocarbons in the system. Our results from the Lockne impact structure show that hydrothermal systems associated with impact structures can support colonization by microbial life. PMID:24336641

Fungal colonization of an Ordovician impact-induced hydrothermal system

NASA Astrophysics Data System (ADS)

Ivarsson, Magnus; Broman, Curt; Sturkell, Erik; Ormö, Jens; Siljeström, Sandra; van Zuilen, Mark; Bengtson, Stefan

2013-12-01

Impacts are common geologic features on the terrestrial planets throughout the solar system, and on at least Earth and Mars impacts have induced hydrothermal convection. Impact-generated hydrothermal systems have been suggested to possess the same life supporting capability as hydrothermal systems associated with volcanic activity. However, evidence of fossil microbial colonization in impact-generated hydrothermal systems is scarce in the literature. Here we report of fossilized microorganisms in association with cavity-grown hydrothermal minerals from the 458 Ma Lockne impact structure, Sweden. Based on morphological characteristics the fossilized microorganisms are interpreted as fungi. We further infer the kerogenization of the microfossils, and thus the life span of the fungi, to be contemporaneous with the hydrothermal activity and migration of hydrocarbons in the system. Our results from the Lockne impact structure show that hydrothermal systems associated with impact structures can support colonization by microbial life.

Fungal colonization of an Ordovician impact-induced hydrothermal system.

PubMed

Ivarsson, Magnus; Broman, Curt; Sturkell, Erik; Ormö, Jens; Siljeström, Sandra; van Zuilen, Mark; Bengtson, Stefan

2013-12-16

Impacts are common geologic features on the terrestrial planets throughout the solar system, and on at least Earth and Mars impacts have induced hydrothermal convection. Impact-generated hydrothermal systems have been suggested to possess the same life supporting capability as hydrothermal systems associated with volcanic activity. However, evidence of fossil microbial colonization in impact-generated hydrothermal systems is scarce in the literature. Here we report of fossilized microorganisms in association with cavity-grown hydrothermal minerals from the 458 Ma Lockne impact structure, Sweden. Based on morphological characteristics the fossilized microorganisms are interpreted as fungi. We further infer the kerogenization of the microfossils, and thus the life span of the fungi, to be contemporaneous with the hydrothermal activity and migration of hydrocarbons in the system. Our results from the Lockne impact structure show that hydrothermal systems associated with impact structures can support colonization by microbial life.

Characterization of nasopharyngeal isolates of type b Haemophilus influenzae from Delhi

PubMed Central

Saikia, Kandarpa K.; Das, Bimal K.; Bewal, Ramesh K.; Kapil, Arti; Arora, N.K.; Sood, Seema

2012-01-01

Background & objectives: Haemophilus influenzae is an important cause of mortality and morbidity among young children in developing countries. Increasing incidence of antibiotic resistance especially production of extended spectrum beta lactamase (ESBL) has made treatment and management of H. influenzae infection more difficult. Nasopharyngeal H. influenzae isolates are excellent surrogate for determination of antibiotic resistance prevalent among invasive H. influenzae isolates. In this study, we characterized nasopharyngeal H. influenzae isolates obtained from healthy school going children in Delhi. Methods: Nasopharyngeal H. influenzae isolates were collected from healthy school going children and subjected to serotyping, fimbrial typing and antibiogram profiling. ESBL production was recorded using phenotypic as well as molecular methods. Multi locus sequence typing (MLST) of 13 representative nasopharyngeal H. influenzae isolates was performed as per guidelines. Results: A significant proportion (26 of 80, 32.5%) of nasopharyngeal isolates of H. influenzae were identified as serotype b. Fimbrial gene (hifA) was detected in 23 (28.75%) isolates. Resistance against commonly prescribed antibiotics (Amp, Tet, Chloro, Septran, Cephalexin) were observed to be high among the nasopharyngeal commensal H. influenzae. Extended spectrum beta lactamase (ESBL) production was observed in a five (6.25%) isolates by both double disk diffusion and molecular typing. MLST identified several novel alleles as well as novel sequence types. Interpretation & conclusions: Our findings showed high resistance against common antibiotics and detection of ESBL in nasopharyngeal H. influenzae isolates collected from normal healthy school going children in Delhi. Detection of H. influenzae type b capsular gene and the presence of fimbrial gene (hif A) suggest virulence potential of these isolates. Discovery of novel alleles and presence of new sequence types (STs) among nasopharyngeal H

Down-regulation of liver-intestine cadherin enhances noscapine-induced apoptosis in human colon cancer cells.

PubMed

Tian, Xia; Liu, Meng; Zhu, Qingxi; Tan, Jie; Liu, Weijie; Wang, Yanfen; Chen, Wei; Zou, Yanli; Cai, Yishan; Han, Zheng; Huang, Xiaodong

2017-09-01

The aim of the present study was to explore the signaling pathway of noscapine which induces apoptosis by blocking liver-intestine cadherin (CDH17) gene in colon cancer SW480 cells. Human colon cancer SW480 cells were transfected with CDH17 interference vector and treatment with 10 µmol/L noscapine. The proliferation and apoptosis of SW480 cells were detected by MTT assay and AnnexinV-FITC/PI flow cytometry kit (BD), respectively. Cell invasion were assessed by transwell assays. Apoptosis related proteins (Cyt-c, Bax, Bcl-2 and Bcl-xL) levels were evaluated by western blot. Compared to the noscapine group, the proliferation was decreased significantly and the apoptosis was increased significantly in SW480 cells of the siCDH17+noscapine group. Cyt-c and Bax protein levels in siCDH17+noscapine group was higher than that of the noscapine group, but Bcl-2 and Bcl-xL protein levels in siCDH17+noscapine group were lower than that of the noscapine group. Moreover, up-expression of CDH17 inhibited the efficacy of noscapine-induced apoptosis in SW480 cells. We inferred that down-expression of extrinsic CDH17 gene can conspicuously promote apoptosis-inducing effects of noscapine on human colon cancer SW480 cells, which is a novel strategy to improve chemotherapeutic effects on colon cancer.

Inhibition of autophagy enhances DENSpm-induced apoptosis in human colon cancer cells in a p53 independent manner.

PubMed

Gurkan, Ajda Coker; Arisan, Elif Damla; Yerlikaya, Pinar Obakan; Ilhan, Halime; Unsal, Narcin Palavan

2018-06-01

One of the recently developed polyamine (PA) analogues, N 1 ,N 11 -diethylnorspermine (DENSpm), has been found to act as an apoptotic inducer in melanoma, breast, prostate and colon cancer cells. Also, its potential to induce autophagy has been established. Unfolded protein responses and starvation of amino acids are known to trigger autophagy. As yet, however, the molecular mechanism underlying PA deficiency-induced autophagy is not fully clarified. Here, we aimed to determine the apoptotic effect of DENSpm after autophagy inhibition by 3-methyladenine (3-MA) or siRNA-mediated Beclin-1 silencing in colon cancer cells. The apoptotic effects of DENSpm after 3-MA treatment or Beclin-1 silencing were determined by PI and AnnexinV/PI staining in conjunction with flow cytometry. Intracellular PA levels were measured by HPLC, whereas autophagy and the expression profiles of PA key players were determined in HCT116, SW480 and HT29 colon cancer cells by Western blotting. We found that DENSpm-induced autophagy was inhibited by 3-MA treatment and Beclin-1 silencing, and that apoptotic cell death was increased by PA depletion and spermidine/spermine N 1 -acetyltransferase (SSAT) upregulation. We also found that autophagy inhibition led to DENSpm-induced apoptosis through Atg5 down-regulation, p62 degradation and LC3 lipidation in both HCT116 and SW480 cells. p53 deficiency did not alter the response of the colon cancer cells to DENSpm-induced apoptotic cell death under autophagy suppression conditions. From our results we conclude that DENSpm-induced apoptotic cell death is increased when autophagy is inhibited by 3-MA or Beclin-1 siRNA through PA depletion and PA catabolic activation in colon cancer cells, regardless p53 mutation status.

Effect of neomycin on azoxymethane-induced colon carcinogenesis in F344 rats.

PubMed

Reddy, B S; Furuya, K; Lowenfels, A

1984-07-01

The effect of oral administration of neomycin (100 and 200 micrograms/ml in drinking water) on colon tumors induced by azoxymethane [(AOM); CAS: 25843-45-2] was studied in female F344 rats. Five-week-old rats were fed NIH-07 diet and given daily in drinking water 0, 100, and 200 micrograms neomycin/ml (0, 100, and 200 ppm). At 7 weeks of age, all animals except vehicle-treated groups received weekly sc injections of 8 mg AOM/kg body weight for 8 weeks. The AOM- or vehicle-treated groups were necropsied 30 weeks after the last injection of AOM. The combined incidence of adenomas and adenocarcinomas of the colon did not differ significantly among the 3 groups. The animals in the groups given 100 and 200 micrograms neomycin had a higher incidence of colon adenocarcinomas than did those in the control group. Colonic and cecal bacterial beta-glucuronidase activity was significantly lower in the group given 200 micrograms neomycin than it was in the control group. The excretion of fecal cholesterol, total bile acids, and deoxycholic acid was increased significantly in animals given 100 and 200 micrograms neomycin as compared to animals given no neomycin. These results suggest that long-term oral administration of neomycin increases the incidence of colon adenocarcinomas.

Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.

PubMed

de Steenhuijsen Piters, Wouter A A; Heinonen, Santtu; Hasrat, Raiza; Bunsow, Eleonora; Smith, Bennett; Suarez-Arrabal, Maria-Carmen; Chaussabel, Damien; Cohen, Daniel M; Sanders, Elisabeth A M; Ramilo, Octavio; Bogaert, Debby; Mejias, Asuncion

2016-11-01

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection. We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity. We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

Peroxisome proliferator-activated receptor gamma agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc1638 N/+ Mlh1+/- double mutant mice.

PubMed

Yang, Kan; Fan, Kun-Hua; Lamprecht, Sergio A; Edelmann, Winfried; Kopelovich, Levy; Kucherlapati, Raju; Lipkin, Martin

2005-09-10

The role of the nuclear peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in colon tumorigenesis remains controversial. Notwithstanding evidence that PPAR-gamma ligands impede murine colorectal carcinogenesis, PPAR-gamma agonists have been shown to enhance in vivo tumor formation in mouse models of human colon cancer. Our study was designed to determine whether troglitazone (TGZ) induces colonic tumor formation in normal C57BL/6J mice and enhances colorectal carcinogenesis in double mutant Apc1638N/+ Mlh1+/- mice fed a standard AIN-76A diet. We report herein that not only does TGZ enhance carcinogenesis in the large intestine of mutant mice predisposed to intestinal carcinogenesis but TGZ also induces colonic tumors in normal mice without gene targeting or carcinogen administration. This observation indicates that preexisting mutational events are not necessary for induction of colonic tumors by activated PPAR-gamma in vivo. (c) 2005 Wiley-Liss, Inc.

[Chemoprotective effect of the alkaloid extract of Melocactus bellavistensis against colon cancer induced in rats using 1,2-dimethylhydrazine].

PubMed

Ríos-León, Karla; Fuertes-Ruiton, Cesar; Arroyo, Jorge; Ruiz, Julio

2017-01-01

To determine the toxicity and chemoprotective effect of the alkaloid extract of Melocactus bellavistensis against colon cancer induced in rats using 1,2-dimethylhydrazine (DMH). The alkaloid extract was obtained from the fleshy part of M. bellavistensis, and an acute toxicity test was then carried out on 30 mice of the Balb C57 strain. To assess its chemoprotective effect, colon cancer was induced in 45 Holtzman rats using DMH according to the following experimental design: one control group received 2 mL/kg sodium polysorbate, and four groups received 20 mg/kg DMH plus 0, 1, 5, or 10 mg/kg M. bellavistensis alkaloid extract. With a sample of 5 g of alkaloid extract, an LD50 greater than 1000 mg/mL was determined in the acute toxicity test. Histological indicators revealed that the 5 and 10 mg/kg doses had significant anti-tumor activity with 100% neoplasia inhibition against DMH- induced colon cancer in rats. Under experimental conditions, the alkaloid extract of M. bellavistensis has a chemoprotective effect against DMH-induced colon cancer in rats.

Osthole induces human nasopharyngeal cancer cells apoptosis through Fas-Fas ligand and mitochondrial pathway.

PubMed

Liu, Pei-Ying; Chang, Dun-Cheng; Lo, Yu-Sheng; Hsi, Yi-Ting; Lin, Chia-Chieh; Chuang, Yi-Ching; Lin, Shu-Hui; Hsieh, Ming-Ju; Chen, Mu-Kuan

2018-04-01

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The present study investigated the activity of osthole in suppressing NPC along with the underlying mechanism. Cell growth inhibition was measured using the MTT assay. Apoptosis was detected through 4',6-diamidino-2-phenylindole staining and flow cytometry. Western blotting was used to identify the signaling pathway. Osthole markedly inhibited cell proliferation and induced apoptosis in the NPC cell line. Western blotting results revealed the increased activation of caspases 3, 8, and 9 and poly (ADP-ribose) polymerase. Osthole treatment significantly reduced the expression of the antiapoptotic protein Bcl-2 and increased the expression of the proapoptotic proteins Bax, Bak, BimL, BimS, and t-Bid. Osthole treatment also increased the expression of Fas, FADD, TNF-R1, TNF-R2, DcR2, RIP, and DR5. In addition, osthole treatment significantly increased the expression levels of phosphorylated ERK1/2 and JNK1/2. These results suggested that osthole exerts cytotoxic effects on NPC cell lines mainly through apoptosis mediated by the Fas-Fas ligand and mitochondrial pathway. Osthole could be a potential anticancer agent for NPC. © 2018 Wiley Periodicals, Inc.

Histological characteristics of collagen denaturation and injuries in bipolar radiofrequency-induced colonic anastomoses.

PubMed

Zhao, Lingxi; Zhuo, Changhua; Song, Chengli; Li, Xinxiang; Zhou, Yu; Shi, Debing

2015-03-01

Bipolar radiofrequency-induced thermo-fusion has been explored as an advanced surgical method for intestinal anastomoses; however, the histological characteristics of collagen denaturation and injuries arising from this process remain unclear. The aim of this study was to investigate the microcosmic changes and tissue damage of fusion regions with various parameters of injury. Ex vivo colons of pigs were fused serosa-serosa on two carrier rings, which were installed on a homemade anastomotic device. Five levels of compressive pressure from 171 to 313 kPa were applied for 5s to fuse the colons under radiofrequency power of 160 W, and then the collagen denaturation of the fused region was examined by transmission electron microscopy. Light microscopy was utilized to observe histological slices that were stained with picrosirius red in order to visualize the tissue injuries under two levels of radiofrequency power (120 vs. 140 W) and operation time (5 vs. 10s). Transmission electron micrographs showed that increased compressive pressure led to thicker denatured collagen fibrils and wider gaps between each collagen fibril. Serosa adhesion regions appeared abundant in collagen. No histological differences were observed when 120 W of power was applied for 5 and 10s. Significant muscle cracking occurred when colons were fused using 140 W for 5s. When the operation time was extended to 10s, 140 W led to tight fusion and less splitting on muscles. These results suggest that higher compressive pressure results in more severe collagen unfolding and also reduces collagen crosslinking in fused colons. Improved radiofrequency power along with operation time could avoid tissue injury upon radiofrequency-induced colonic anastomoses. Copyright © 2014 Elsevier GmbH. All rights reserved.

Can Platelet and Leukocyte Indicators Give Us an Idea about Distant Metastasis in Nasopharyngeal Cancer?

PubMed

Arıcıgil, Mitat; Dündar, Mehmet Akif; Yücel, Abitter; Arbağ, Hamdi; Aziz, Suhayb Kuria

This study aimes to evaluate platelet and leucocyte indicators, such as the mean platelet volume, platelet distribution width, plateletcrit, white blood cell count, neutrophil to lymphocyte ratio in nasopharyngeal cancer patients and also to evaluate the relationship between these indicators and nasopharyngeal cancer with distant metastasis. The medical records of 118 patients diagnosed with nasopharyngeal cancer in our hospital between January 2006 and August 2015 were reviewed. The nasopharyngeal cancer group was further sub grouped according to the presence or absence of distant metastasis and TNM (tumour - T, node - N, metastasis - M) classification. A control group consisted of 120 healthy patients. The platelet and leucocyte values at the time of the initial diagnosis were recorded. Neutrophil to lymphocyte ratio and platelet distribution width values were significantly higher in the nasopharyngeal cancer group. But only platelet distribution width values were significantly higher in the nasopharyngeal cancer group with distant metastasis compared to the nasopharyngeal cancer group without distant metastasis. Neutrophil to lymphocyte ratio and platelet distribution width values may increase in nasopharyngeal cancer. But only the platelet distribution width values may give us an idea about the distant metastasis in nasopharyngeal cancer.

Nasopharyngeal colonization by potentially pathogenic bacteria found in healthy semi-captive wild-born chimpanzees in Uganda.

PubMed

Mugisha, Lawrence; Köndgen, Sophie; Kaddu-Mulindwa, Deogratias; Gaffikin, Lynne; Leendertz, Fabian H

2014-02-01

Information on the chimpanzee nasopharygeal colonization in captive sanctuaries and in the wild is rare. This study was undertaken to establish the nasopharygeal colonization and potential bacterial pathogens in sanctuary chimpanzees as a basis for improving chimpanzee and employee health. Nasopharygeal colonization of 39 healthy chimpanzees were analyzed by microbiological cultivation method and polymerase chain reaction (PCR) targeting the bacterial 16S rRNA gene. We report four major phyla dominated by Proteobacteria (50%), Fermicutes (35.7%), Bacteriodes (7.1%), and Cynobacteria (7.1%) in healthy semi-captive chimpanzees. Further classification based on 7-base oligomers revealed the following genera: Streptococcus, Veillonella, Neisseria, Prevotella, Kingella and unclassified Cynobacteria, Actinobacillus, Bacteriodes and Pasteurellaceae. On microbiological cultivation we were able to identify and characterize some of the bacteria to species level as Klebsiella pneumonie and Pseudomonas aeruginosa being dominant bacteria with 54.7% and 50% colonization, respectively. Of these, Streptococcus, Neisseria, Klebsiella, and Haemophillus have representatives known to potentially cause severe respiratory disease. Our data present important information on chimpanzee nasopharygeal colonization as a guide to understanding disease processes and pharmaceutical therapies required for improving the health of chimpanzees. The results from this study will guide the processes to improve procedures for routine management of sanctuary chimpanzees and use it as a basis for evaluation of future reintroduction possibilities. © 2013 Wiley Periodicals, Inc.

Acetylcholine-induced activation of M3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells.

PubMed

Xie, Guofeng; Cheng, Kunrong; Shant, Jasleen; Raufman, Jean-Pierre

2009-04-01

Previously, we showed that ACh-induced proliferation of human colon cancer cells is mediated by transactivation of epidermal growth factor (EGF) receptors (EGFRs). In the present study, we elucidate the molecular mechanism underlying this action. ACh-induced proliferation of H508 colon cancer cells, which express exclusively M3 muscarinic receptors (M3Rs), was attenuated by anti-EGFR ligand binding domain antibody, a broad-spectrum matrix metalloproteinase (MMP) inhibitor, anti-MMP7 antibody, a diphtheria toxin analog that blocks release of an EGFR ligand [heparin-binding EGF-like growth factor (HBEGF)], and anti-HBEGF antibody. Conditioned media from ACh-treated H508 cells induced proliferation of SNU-C4 colon cancer cells that express EGFR but not M3R. These actions were attenuated by an EGFR inhibitor and by anti-EGFR and anti-HBEGF antibodies. In H508, but not SNU-C4, colon cancer cells, ACh caused a striking dose- and time-dependent increase in levels of MMP7 mRNA and MMP7 protein. Similarly, ACh induced robust MMP1 and MMP10 gene transcription. ACh-induced MMP1, MMP7, and MMP10 gene transcription was attenuated by atropine, anti-EGFR antibody, and chemical inhibitors of EGFR and ERK activation. In contrast, inhibitors of phosphatidylinositol 3-kinase and NF-kappaB activation did not alter MMP gene transcription. Collectively, these findings indicate that MMP7-catalyzed release of HBEGF mediates ACh-induced transactivation of EGFR and consequent proliferation of colon cancer cells. ACh-induced activation of EGFR and downstream ERK signaling also regulates transcriptional activation of MMP7, thereby identifying a novel feed-forward mechanism for neoplastic cell proliferation.

Acetylcholine-induced activation of M3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells

PubMed Central

Xie, Guofeng; Cheng, Kunrong; Shant, Jasleen; Raufman, Jean-Pierre

2009-01-01

Previously, we showed that ACh-induced proliferation of human colon cancer cells is mediated by transactivation of epidermal growth factor (EGF) receptors (EGFRs). In the present study, we elucidate the molecular mechanism underlying this action. ACh-induced proliferation of H508 colon cancer cells, which express exclusively M3 muscarinic receptors (M3Rs), was attenuated by anti-EGFR ligand binding domain antibody, a broad-spectrum matrix metalloproteinase (MMP) inhibitor, anti-MMP7 antibody, a diphtheria toxin analog that blocks release of an EGFR ligand [heparin-binding EGF-like growth factor (HBEGF)], and anti-HBEGF antibody. Conditioned media from ACh-treated H508 cells induced proliferation of SNU-C4 colon cancer cells that express EGFR but not M3R. These actions were attenuated by an EGFR inhibitor and by anti-EGFR and anti-HBEGF antibodies. In H508, but not SNU-C4, colon cancer cells, ACh caused a striking dose- and time-dependent increase in levels of MMP7 mRNA and MMP7 protein. Similarly, ACh induced robust MMP1 and MMP10 gene transcription. ACh-induced MMP1, MMP7, and MMP10 gene transcription was attenuated by atropine, anti-EGFR antibody, and chemical inhibitors of EGFR and ERK activation. In contrast, inhibitors of phosphatidylinositol 3-kinase and NF-κB activation did not alter MMP gene transcription. Collectively, these findings indicate that MMP7-catalyzed release of HBEGF mediates ACh-induced transactivation of EGFR and consequent proliferation of colon cancer cells. ACh-induced activation of EGFR and downstream ERK signaling also regulates transcriptional activation of MMP7, thereby identifying a novel feed-forward mechanism for neoplastic cell proliferation. PMID:19221016

Flagellin Induces β-Defensin 2 in Human Colonic Ex vivo Infection with Enterohemorrhagic Escherichia coli

PubMed Central

Lewis, Steven B.; Prior, Alison; Ellis, Samuel J.; Cook, Vivienne; Chan, Simon S. M.; Gelson, William; Schüller, Stephanie

2016-01-01

Enterohemorrhagic E.coli (EHEC) is an important foodborne pathogen in the developed world and can cause life-threatening disease particularly in children. EHEC persists in the human gut by adhering intimately to colonic epithelium and forming characteristic attaching/effacing lesions. In this study, we investigated the innate immune response to EHEC infection with particular focus on antimicrobial peptide and protein expression by colonic epithelium. Using a novel human colonic biopsy model and polarized T84 colon carcinoma cells, we found that EHEC infection induced expression of human β-defensin 2 (hBD2), whereas hBD1, hBD3, LL-37, and lysozyme remained unchanged. Infection with specific EHEC deletion mutants demonstrated that this was dependent on flagellin, and apical exposure to purified flagellin was sufficient to stimulate hBD2 and also interleukin (IL)-8 expression ex vivo and in vitro. Flagellin-mediated hBD2 induction was significantly reduced by inhibitors of NF-κB, MAP kinase p38 and JNK but not ERK1/2. Interestingly, IL-8 secretion by polarized T84 cells was vectorial depending on the side of stimulation, and apical exposure to EHEC or flagellin resulted in apical IL-8 release. Our results demonstrate that EHEC only induces a modest immune response in human colonic epithelium characterized by flagellin-dependent induction of hBD2 and low levels of IL-8. PMID:27446815

Leptin induces SIRT1 expression through activation of NF-E2-related factor 2: Implications for obesity-associated colon carcinogenesis.

PubMed

Song, Na-Young; Lee, Yeon-Hwa; Na, Hye-Kyung; Baek, Jeong-Heum; Surh, Young-Joon

2018-07-01

Leptin, a representative adipokine secreted from the white adipose tissue, is considered as a potential linker between obesity and cancer. SIRT1 is an NAD + -dependent histone/protein deacetylase speculated to function as an oncogene. In the present study, we found that leptin signaling-defective ob/ob and db/db mice had lower colonic expression of SIRT1 compared with leptin signaling-intact C57BL/6J mice, implying that leptin signaling is crucial for SIRT1 expression in vivo. Moreover, leptin induced up-regulation of SIRT1 in human colon cancer (HCT-116) cells. Leptin stimulated migration and invasion of cultured HCT-116 cells and tumor growth in the xenograft assay, and these effects were abrogated by a SIRT1 inhibitor sirtinol, suggesting that SIRT1 plays a role in leptin-induced colon carcinogenesis. Leptin-induced SIRT1 expression was regulated by the redox-sensitive transcription factor NF-E2-related factor 2 (Nrf2). Leptin stimulated nuclear accumulation of Nrf2 as well as its binding to the antioxidant response elements located in the SIRT1 promoter. Moreover, siRNA knockdown of Nrf2 abrogated the leptin-induced SIRT1 expression. Notably, SIRT1 was significantly reduced in colon tissues of Nrf2-null mice, lending further support to Nrf2-dependent SIRT1 expression. Expression of leptin, Nrf2 and SIRT1 was coordinately increased in human colon tumor tissues. In conclusion, leptin might play a role in colon carcinogenesis by inducing Nrf2-dependent SIRT1 overexpression. Copyright © 2018 Elsevier Inc. All rights reserved.

Trinitrobenzenesulfonic Acid Colitis Induces Changes in the Contractile Response of Circular Smooth Muscle in the Distal Colon

DTIC Science & Technology

1996-03-27

contractile response of circular smooth muscle in the rat distal colon" Name of Candidate: Jeanette M. Hosseini Doctor of Philosophy Degree 27 March 1996... muscle in the rat distal colon" beyond brief excerpts is with the pennission of the copyright owner, and will save and hold harmless the Unifonned...induces changes in the contractile response of circular smooth muscle 10 the rat colon. Jeanette Marie Hosseini, 1996 Dissertation directed by: Terez

Boletus edulis ribonucleic acid - a potent apoptosis inducer in human colon adenocarcinoma cells.

PubMed

Lemieszek, Marta Kinga; Ribeiro, Miguel; Guichard Alves, Helena; Marques, Guilhermina; Nunes, Fernando Milheiro; Rzeski, Wojciech

2016-07-13

Despite the large popularity of the Boletus edulis mushroom, little is known about its influence on human health and the possibilities of its therapeutic use. Nevertheless, several reports revealed the usefulness of biopolymers isolated from it in cancer treatment. Our previous studies have shown that B. edulis water soluble biopolymers are not toxic against normal colon epithelial cells (CCD841 CoTr) and at the same concentration range elicited a very prominent antiproliferative effect in colon cancer cells (LS180) which was accompanied with cell cycle arrest in the G0/G1 phase. The purpose of the present study was to verify the proapoptotic properties of a selected fraction from B. edulis - BE3, as well as determine its chemical nature. The BE3 fraction was extracted with hot water and purified by anion-exchange chromatography. Further chemical examinations revealed that BE3 consists mainly of ribonucleic acid (59.1%). The ability of BE3 to induce programmed cell death was examined in human colon cancer cell lines LS180 and HT-29 by measuring caspase activation, DNA fragmentation and expression of BAX, BCL2, TP53 and CDKN1A genes. The sensitivity of colon cancer cells with silenced BAX, TP53 and CDKN1A expression to BE3 treatment was also evaluated. We have demonstrated for the first time that the BE3 fraction is a potent apoptosis inducer in human colon cancer cells. The revealed mechanism of apoptosis triggering was dependent on the presence of functional p53 and consequently was a little different in investigated cell lines. Our results indicated that BE3 stimulated proapoptotic genes BAX (LS180, HT-29), TP53 (LS180) and CDKN1A (HT-29) while at the same time silenced the expression of the key prosurvival gene BCL2 (LS180, HT-29). The obtained results indicate the high therapeutic potential of the BE3 fraction against colon cancer, yet it is necessary to further confirm fraction efficacy and safety in animal and clinical studies.

Boswellia serrata resin extract alleviates azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis.

PubMed

Chou, Ya-Chun; Suh, Joon Hyuk; Wang, Yu; Pahwa, Manoj; Badmaev, Vladimir; Ho, Chi-Tang; Pan, Min-Hsiung

2017-09-01

Boswellia serrata (BS) resin is a popular dietary supplement for joint nourishment. In this study, we investigated the chemopreventive effects of dietary BS extract and its impact of gut microbiota on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated colon cancer in mice. Male ICR mice were injected with AOM and 2% DSS via drinking water. The mice were fed with 0.25 or 0.5% BS extract, and colonic tissue were collected at 15 weeks. The main effective components of BS supercritical CO 2 extraction were analyzed by LC-MS/MS are boswellic acids. We found that treatment with BS extract significantly reduce the colonic tumor formation. Western blot and histological analysis revealed that dietary BS extract could markedly reduce the inflammation associated protein levels expression. Furthermore, BS extract reduced cell proliferation via inhibiting phosphorylation level of protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β), and downregulation of cyclin D1. In addition, BS extract also altered the composition of gut microbiota by enhancing the proportion of Clostridiales and reducing the percentage of Bacteroidales. In summary, BS extract decreased the protein levels of inflammative enzymes such as inducible nitric oxide synthase and cyclooxygenase-2 in colonic mucosa. It also mediated Akt/GSK3β/cyclin D1 signaling pathway and altered the composition of gut microbiota to alleviate tumor growth. Taken together, this study suggests that BS extract has great potential to suppress colon tumorigenesis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Resistant starch prevents tumorigenesis of dimethylhydrazine-induced colon tumors via regulation of an ER stress-mediated mitochondrial apoptosis pathway.

PubMed

Wang, Qiuyu; Wang, Peng; Xiao, Zhigang

2018-04-01

Resistant starch is as common soluble fiber that escapes digestion in the small intestine and can regulate intestinal function, metabolism of blood glucose and lipids, and may prevent tumorigenesis of gastrointestinal cancer. Epidemiology and other evidence have suggested that resistant starch may prevent colon cancer development. The aim of the current study was to explore the ameliorative effects and potential mechanisms of resistant starch in the tumorigenesis of colon tumors induced by dimethylhydrazine in C57BL/6 mice. Western blot analysis, ELISA, microscopy, immunofluorescence and immunohistochemistry were used to analyze the efficacy of resistant starch on the metabolic balance in the colon and tumorigenesis of colon tumors. The results demonstrated that a diet containing resistant starch decreased the animal body weight and reduced free ammonia, pH and short chain fatty acids in feces compared with mice that received a standard diet. Resistant starch reduced the incidence of colon tumors and suppressed the expression of carcinogenesis‑associated proteins, including heat shock protein 25, protein kinase C‑d and gastrointestinal glutathione peroxidase in colon epithelial cells compared with standard starch and control groups. Colon tumor cells proliferation and dedifferentiation were significantly decreased by a resistant starch diet. The results also demonstrated that resistant starch increased the apoptosis of colon tumor cells through regulation of apoptosis‑associated gene expression levels in colon tumor cells. Oxidative stress and endoplasmic reticulum stress were upregulated, and elevation eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor‑4 and secretase‑β expression levels were increased in the resistant starch diet group. Additionally, the activity of eIF2α and PERK were increased in colon tumor cells from mice that had received resistant starch. Increasing DNA damage‑inducible transcript 3

Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon.

PubMed

Ijssennagger, Noortje; Belzer, Clara; Hooiveld, Guido J; Dekker, Jan; van Mil, Saskia W C; Müller, Michael; Kleerebezem, Michiel; van der Meer, Roelof

2015-08-11

Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function.

Chemoprevention by Probiotics During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats.

PubMed

Walia, Sohini; Kamal, Rozy; Dhawan, D K; Kanwar, S S

2018-04-01

Probiotics are believed to have properties that lower the risk of colon cancer. However, the mechanisms by which they exert their beneficial effects are relatively unknown. To assess the impact of probiotics in preventing induction of colon carcinogenesis in rats. The rats were divided into six groups viz., normal control, Lactobacillus plantarum (AdF10)-treated, Lactobacillus rhamnosus GG (LGG)-treated, 1,2-dimethylhydrazine (DMH)-treated, L. plantarum (AdF10) + DMH-treated and L. rhamnosus GG (LGG) + DMH-treated. Both the probiotics were supplemented daily at a dose of 2 × 10 10 cells per day. DMH at a dose of 30 mg/kg body weight was administered subcutaneously twice a week for the first 4 weeks and then once every week for a duration of 16 weeks. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase as protein expression of genes involved in apoptosis were assessed during DMH-induced colon carcinogenesis in rats. DMH treatment decreased the activity of GSH, GPx, GST, SOD and catalase. However, AdF10 and LGG supplementation to DMH-treated rats significantly increased the activity of these enzymes. Further, DMH treatment revealed alterations in the protein expressions of various genes involved in the p53-mediated apoptotic pathway such as p53, p21, Bcl-2, Bax, caspase-9 and caspase-3, which, however, were shifted towards normal control levels upon simultaneous supplementation with probiotics. The present study suggests that probiotics can provide protection against oxidative stress and apoptotic-related protein disregulation during experimentally induced colon carcinogenesis.

Relationships between genetic polymorphisms in inflammation-related factor gene and the pathogenesis of nasopharyngeal cancer.

PubMed

Qu, Yan-Li; Yu, Hong; Chen, Yan-Zhi; Zhao, Yu-Xia; Chen, Guang-Jun; Bai, Lu; Liu, Dan; Su, Hong-Xin; Wang, He-Tong

2014-09-01

Our study aims to discuss the association between inflammation-related factors such as single nucleotide polymorphisms (SNPs) with susceptibility and recurrence in nasopharyngeal carcinoma. We used Taqman real-time polymerase chain reaction (PCR) to characterize the genetic variation of five SNPs in 194 nasopharyngeal carcinoma patients and 231 healthy subjects. All statistical analysis is performed with statistical product and service solutions v13.0; odds ratio (OR) value and 95 % confidence interval (CI) were calculated. There is no relationship between TGFβ1 -869 T/C, IL-6 -634C/G, TGFβ1 -509C/T, IL1 -511C/T and nasopharyngeal carcinoma susceptibility. Both single factor and multiple factors analysis showed that IL1a -889 T/T genotype is significantly associated with nasopharyngeal carcinoma in decreasing the risk of nasopharyngeal carcinoma. A highly significant association was found between IL1a -889 T/T genotype and protective genotype as defined by various pathological types. This is more obvious in the protective genotype of the non-keratin-type squamous carcinoma undifferentiated type. We also discovered that genotype G/G and C/G + G/G of IL6 -634 gene are associated with reduced recurrence of nasopharyngeal carcinoma. IL1a -889 gene polymorphism and susceptibility is related to nasopharyngeal carcinoma and can potentially decrease the risk of nasopharyngeal carcinoma in the Han Chinese population in north China. IL1-889 TT genotype is protective genotype for nasopharyngeal carcinoma. We have provided evidence that the GG genotype of the IL6 -634 gene is associated with recurrent risk of nasopharyngeal carcinoma. The G allele is the protective gene of nasopharyngeal carcinoma recurrence.

High-grade malignant transformation of a radiation-naïve nasopharyngeal angiofibroma.

PubMed

Allensworth, Jordan J; Troob, Scott H; Lanciault, Christian; Andersen, Peter E

2016-04-01

Nasopharyngeal angiofibromas are typically considered benign vascular neoplasms, with descriptions of high-grade sarcomatous change found only in lesions with prior radiotherapy. We describe the first reported case of high-grade malignant change in a nasopharyngeal angiofibroma naive to radiation. A 45-year-old man presented with left-sided nasal congestion and fullness and was found to have a left-sided nasopharyngeal mass with intracranial extension on CT scan. A biopsy of the mass revealed nasopharyngeal angiofibroma. The patient opted for MRI surveillance, which revealed interval growth 3 years later. Decompression surgery revealed only angiofibroma, but resection 9 months later demonstrated high-grade sarcoma and concomitant angiofibroma. The patient had residual disease which progressed through chemoradiation, and is now pursuing clinical trial enrollment. Malignant transformation of nasopharyngeal angiofibroma is extremely rare. As highlighted by this report, high-grade undifferentiated lesions may arise in tumors without previous radiation. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2425-E2427, 2016. © 2016 Wiley Periodicals, Inc.

Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway.

PubMed

Lin, Yu-Tsai; Wang, Hung-Chen; Hsu, Yi-Chiang; Cho, Chung-Lung; Yang, Ming-Yu; Chien, Chih-Yen

2017-06-23

Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells. Exposure to capsaicin inhibited cancer cell growth and increased G1 phase cell cycle arrest. Western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) were used to measure capsaicin-induced autophagy via involvement of the class III PI3K/Beclin-1/Bcl-2 signaling pathway. Capsaicin induced autophagy by increasing levels of the autophagy markers LC3-II and Atg5, enhancing p62 and Fap-1 degradation and increasing caspase-3 activity to induce apoptosis, suggesting a correlation of blocking the PI3K/Akt/mTOR pathway with the above-mentioned anticancer activities. Taken together, these data confirm that capsaicin inhibited the growth of human NPC cells and induced autophagy, supporting its potential as a therapeutic agent for cancer.

Age-related differential responses to curcumin-induced apoptosis during the initiation of colon cancer in rats.

PubMed

Kwon, Youngjoo; Magnuson, Bernadene A

2009-02-01

Curcumin is a widely-used dietary supplement and a chemopreventive agent for various cancers. Pre-clinical chemopreventive studies rarely consider the effect of aging. We previously reported that unlike young animals, curcumin is ineffective in middle-aged rats for colon chemoprevention. This study investigated whether resistance to apoptosis during cancer initiation contributes to this age-dependent effect. Young, middle-aged, and old F344 rats were fed either curcumin (0.6%) or control diet. Colonic apoptosis was evaluated 0, 8, and 16 h after azoxymethane (AOM) injection. Colonic Hsp70 mRNA levels, caspase-9 activity, cell proliferation, and crypt morphology were measured. In AOM-treated rats, only middle-aged rats were resistant to curcumin-induced apoptosis whereas cell proliferation was reduced by curcumin in all ages. Curcumin-induced apoptosis was mediated by caspase-9 in young but not older rats. Transcriptional Hsp70 expression was induced in only young rats and was suppressed by curcumin. Therefore, the age-related difference in curcumin chemoprevention is due to a differential response in induction of apoptosis. The mitochondria-dependent pathway seems to mediate curcumin-induced apoptosis in young but not older animals. Hsp70 expression was not related with resistance to curcumin-induced apoptosis. Understanding age-related differences in the apoptotic response may lead to improved translation from pre-clinical animal studies to humans.

Effect of early measles vaccine on pneumococcal colonization: A randomized trial from Guinea-Bissau

PubMed Central

Byberg, Stine; Hervig Jacobsen, Lars; Bjerregaard-Andersen, Morten; Jensen, Aksel Karl Georg; Martins, Cesario; Aaby, Peter; Skov Jensen, Jørgen; Stabell Benn, Christine; Whittle, Hilton

2017-01-01

Background Measles vaccine (MV) may have non-specific beneficial effects for child health and particularly seems to prevent respiratory infections. Streptococcus pneumoniae is the leading cause of bacterial pneumonia among children worldwide, and nasopharyngeal colonization precedes infection. Objective We investigated whether providing early MV at 18 weeks of age reduced pneumococcal colonization and/or density up to 9 months of age. Method The study was conducted in 2013–2014 in Guinea-Bissau. Pneumococcal vaccine was not part of the vaccination program. Infants aged 18 weeks were block-randomized 2:1 to early or no early MV; at age 9 months, all children were offered MV as per current policy. Nasopharyngeal swabs were taken at baseline, age 6.5 months, and age 9 months. Pneumococcal density was determined by q-PCR. Prevalence ratios of pneumococcal colonization and recent antibiotic treatment (yes/no) by age 6.5 months (PR6.5) and age 9 months (PR9) were estimated using Poisson regression with robust variance estimates while the pneumococcal geometric mean ratio (GMR6.5 and GMR9) was obtained using OLS regression. Results Analyses included 512 children; 346 early MV-children and 166 controls. At enrolment, the pneumococcal colonization prevalence was 80% (411/512). Comparing early MV-children with controls, the PR6.5 was 1.02 (95%CI = 0.94–1.10), and the PR9 was 1.04 (0.96–1.12). The GMR6.5 was 1.02 (0.55–1.89), and the GMR9 was 0.69 (0.39–1.21). Early MV-children tended to be less frequently treated with antibiotics prior to follow up (PR6.5 0.60 (0.34–1.05) and PR9 0.87 (0.50–1.53)). Antibiotic treatment was associated with considerably lower colonization rates, PR6.5 0.85 (0.71–1.01) and PR9 0.66 (0.52–0.84), as well as lower pneumococcal density, GMR6.5 0.32 (0.12–0.86) and GMR9 0.52 (0.18–1.52). Conclusion Early MV at age 18 weeks had no measurable effect on pneumococcal colonization prevalence or density. Higher consumption of

Colon carcinogenesis: influence of Western diet-induced obesity and targeting stem cells using dietary bioactive compounds.

PubMed

Kasdagly, Maria; Radhakrishnan, Sridhar; Reddivari, Lavanya; Veeramachaneni, D N Rao; Vanamala, Jairam

2014-01-01

Colon cancer strikes more than 1 million people annually and is responsible for more than 500,000 cancer deaths worldwide. Recent evidence suggests that the majority of malignancies, including colon cancer are driven by cancer stem cells (CSCs) that are resistant to current chemotherapeutic approaches leading to cancer relapse. Wnt signaling plays a critical role in colon stem cell renewal and carcinogenesis. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a Wnt target gene, and aldehyde dehydrogenase 1 B1 (ALDH1B1) are good markers for normal and malignant human colon stem cells. Diet contributes to 20% to 42% of all human cancers and 50% to 90% of colon cancer. Recent evidence shows that the Western diet has a causative link to colon cancer; however, mechanisms of action are not fully elucidated. Western diet-induced obesity elevates systemic insulin-like growth factor-1 and insulin levels, which could lead to elevated proliferation and suppressed apoptosis of CSCs through PI3K/AKT/Wnt pathway. Although conventional chemotherapy targets the PI3K/AKT pathways and can significantly reduce tumor size, it fails to eliminate CSCs and has serious side effects. Dietary bioactive compounds such as grape seed extract, curcumin, lycopene, and resveratrol have promising chemopreventive effects, without serious side effects on various types of cancers due to their direct and indirect actions on CSC self-renewal pathways such as the Wnt pathway. Understanding the role of CSCs in diet-induced colon cancer will aid in development of evidence-based dietary chemopreventive strategies and/or therapeutic agents targeting CSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Recurrence of a nasopharyngeal carcinoma manifesting as a cerebellopontine angle mass.

PubMed

Kong, Min Han; Jeevanan, Jahendran; Jegan, Thanabalan

2013-12-01

As many as 31% of patients with nasopharyngeal carcinoma present with intracranial extension. Despite this high percentage, extension to the cerebellopontine angle is rare. The mechanism of tumor spread to the cerebellopontine angle is not completely understood. The most likely mechanism is direct extension to the skull base with involvement of the petrous apex and further extension posteriorly via the medial tentorial edge. We report the case of a 46-year-old woman with nasopharyngeal carcinoma who had been treated initially with chemoradiation and subsequently with stereotactic radiosurgery for residual tumor. One year later, she presented with an intracranial recurrence of the nasopharyngeal carcinoma in the cerebellopontine angle; the recurrence mimicked a benign tumor on magnetic resonance imaging. The tumor was ultimately diagnosed as an undifferentiated carcinoma of nasopharyngeal origin. She was treated with palliative chemotherapy.

Emodin suppresses the nasopharyngeal carcinoma cells by targeting the chloride channels.

PubMed

Ma, Lianshun; Yang, Yaping; Yin, Zizhang; Liu, Mei; Wang, Liwei; Chen, Lixin; Zhu, Linyan; Yang, Haifeng

2017-06-01

Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum. Recent studies demonstrated that emodin has anti-cancer activity in different kinds of human cancer cell lines. However, the underlying mechanism has not been very well studied. Our previous studies showed chloride channels is an important target of anti-cancer drugs. Therefore, the purpose of this research was aimed to explore the role of chloride channels involving in the anti-cancer activity of emodin. The proliferation, cell cycle arrest and apoptosis of poorly differentiated human nasopharyngeal carcinoma cells (CNE-2Z) and normal nasopharyngeal epithelial cells (NP69-SV40T) were detected by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT)and flow cytometry. The results indicated that emodin inhibited the CNE-2Z cell growth more significantly than NP69-SV40T cells and induced cell cycle arrest and apoptosis in CNE-2Z cells but not in NP69-SV40T cells. Chloride channel blocker 5-nitro-2-(3-phenylprop ylamino)-benzoate (NPPB) or tamoxifen both can prevent the apoptosis of CNE-2Z cells induced by emodin. Optical microscope and atomic force microscope (AFM) demonstrated that emodin can induce apoptotic volume decrease (AVD) and ultrastructure changes in CNE-2Z cell and inhibited by chloride channel blocker. These data could be a further evidence of chloride channel for preventing CNE-2Z cells from apoptosis induced by emodin. Whole cell patch clamp study also demonstrated that emodin can activate chloride channel in CNE-2Z cells but not in NP69-SV40T cells. Furthermore, the activated chloride currents can also be inhibited by chloride channel blockers indicating that chloride channel may be the potential target molecular of emodin exerting its anti-tumor efficiency in CNE-2Z cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells

PubMed Central

Lugini, Luana; Valtieri, Mauro; Federici, Cristina; Cecchetti, Serena; Meschini, Stefania; Condello, Maria; Signore, Michele; Fais, Stefano

2016-01-01

Background Cancer cells, including colorectal cancer ones (CRC), release high amounts of nanovesicles (exosomes), delivering biochemical messages for paracrine or systemic crosstalk. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression. Results CRC exosomes induce in cMSCs: i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of CEA. Colon cancer derived MSCs, which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes. Materials and Methods Tissue specific colonic (c)MSCs were exposed to primary or metastatic CRC exosomes and analysed by light and electron microscopy, proliferation in 2D and 3D cultures, migration and invasion assays, Western blot and confocal microscopy for vacuolar H+-ATPase expression. Conclusions CRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. Our results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer. PMID:27418137

Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells.

PubMed

Lugini, Luana; Valtieri, Mauro; Federici, Cristina; Cecchetti, Serena; Meschini, Stefania; Condello, Maria; Signore, Michele; Fais, Stefano

2016-08-02

Cancer cells, including colorectal cancer ones (CRC), release high amounts of nanovesicles (exosomes), delivering biochemical messages for paracrine or systemic crosstalk. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression. CRC exosomes induce in cMSCs: i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of CEA. Colon cancer derived MSCs, which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes. Tissue specific colonic (c)MSCs were exposed to primary or metastatic CRC exosomes and analysed by light and electron microscopy, proliferation in 2D and 3D cultures, migration and invasion assays, Western blot and confocal microscopy for vacuolar H+-ATPase expression. CRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. Our results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer.

Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation

PubMed Central

Gareau, Mélanie G; Jury, Jennifer; MacQueen, Glenda; Sherman, Philip M; Perdue, Mary H

2007-01-01

Background We previously showed that neonatal maternal separation (MS) of rat pups causes immediate and long‐term changes in intestinal physiology. Aim To examine if administration of probiotics affects MS‐induced gut dysfunction. Methods MS pups were separated from the dam for 3 h/day from days 4 to 19; non‐separated (NS) pups served as controls. Twice per day during the separation period, 108 probiotic organisms (two strains of Lactobacillus species) were administered to MS and NS pups; vehicle‐treated pups received saline. Studies were conducted on day 20, when blood was collected for corticosterone measurement as an indication of hypothalamus–pituitary–adrenal (HPA) axis activity, and colonic function was studied in tissues mounted in Ussing chambers. Ion transport was indicated by baseline and stimulated short‐circuit current (Isc); macromolecular permeability was measured by flux of horseradish peroxidase (HRP) across colonic tissues; and bacterial adherence/penetration into the mucosa was quantified by culturing tissues in selective media. Colonic function and host defence were also evaluated at day 60. Results Isc and HRP flux were significantly higher in the colon of MS versus NS pups. There was increased adhesion/penetration of total bacteria in MS pups, but a significant reduction in Lactobacillus species. Probiotic administration ameliorated the MS‐induced gut functional abnormalities and bacterial adhesion/penetration at both day 20 and 60, and reduced the elevated corticosterone levels at day 20. Conclusions The results indicate that altered enteric flora are responsible for colonic pathophysiology. Probiotics improve gut dysfunction induced by MS, at least in part by normalisation of HPA axis activity. PMID:17339238

Nasopharyngeal and hypopharyngeal carcinoma risk among immigrants in Sweden.

PubMed

Mousavi, Seyed Mohsen; Sundquist, Jan; Hemminki, Kari

2010-12-15

Environmental exposures, particularly infection with Epstein-Barr virus (EBV) and tobacco, are known risk factors for oral cancer. Studies in migrants may provide valuable insight into the environmental and genetic etiology of cancer. We wanted to define nasopharyngeal and hypopharyngeal carcinoma among immigrants in Sweden. The nationwide Swedish Family-Cancer Database (FCD) was used to calculate standardized incidence ratios (SIRs) for nasopharyngeal and hypopharyngeal carcinomas among the first-generation immigrants compared to the native Swedes. The FCD included 1969 and 691 cases of nasopharyngeal and hypopharyngeal carcinoma in the male and female Swedes and 178 and 65 cases in immigrants, respectively. The median age at diagnosis (years) was 63 among Swedes and 55 among immigrants. The risk of nasopharyngeal carcinoma was significantly higher in male (SIR = 35.6) and female (24.6) Southeast Asians, male (12.4) and female (34.7) North Africans, male (4.9) and female (10.9) Asian Arabs and some other male Asians immigrants (6.2 to 6.7). Among immigrants from European countries, only the men from former Yugoslavian showed an elevated risk (2.7). Hypopharyngeal carcinoma risk was only increased among the male immigrants from the Indian Subcontinent (5.4). Early life infection with EBV in countries of origin and probably a minor contribution by tobacco smoking may be the main environmental exposures influencing nasopharyngeal carcinoma risks among immigrants to Sweden. The high rates of hypopharyngeal carcinoma among Indian immigrants may point to a continued using of smokeless tobacco. Copyright © 2010 UICC.

α-melanocyte stimulating hormone modulates the central acyl ghrelin-induced stimulation of feeding, gastrointestinal motility, and colonic secretion.

PubMed

Huang, Hsien-Hao; Chen, Liang-Yu; Doong, Ming-Luen; Chang, Shi-Chuan; Chen, Chih-Yen

2017-01-01

Acyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of α-melanocyte stimulating hormone (α-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect. This study aimed to investigate the modulating effect of α-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats. We examined the effects of α-MSH and acyl ghrelin on food intake, gastric emptying, small intestinal transit, colonic motility, and secretion in conscious rats with a chronic implant of ICV catheters. ICV injection of O - n -octanoylated ghrelin (0.1 nmol/rat) significantly increased the cumulative food intake up to 8 h ( P <0.01), enhanced non-nutrient semi-liquid gastric emptying ( P <0.001), increased the geometric center and running percentage of small intestinal transit ( P <0.001), accelerated colonic transit time ( P <0.05), and increased fecal pellet output ( P <0.01) and total fecal weight ( P <0.01). Pretreatment with ICV injection of α-MSH (1.0 and 2.0 nmol/rat) attenuated the acyl ghrelin-induced hyperphagic effect, fecal pellet output, and total fecal weight, while higher dose of α-MSH (2.0 nmol/rat) attenuated the increase in the geometric center of small intestinal transit ( P <0.01). However, neither dose of α-MSH altered acyl ghrelin-stimulated gastroprokinetic effect, increase in the running percentage of small intestinal transit, nor accelerated colonic transit time. α-MSH is involved in central acyl ghrelin-elicited feeding, small intestinal transit, fecal pellet output, and fecal weight. α-MSH does not affect central acyl ghrelin-induced acceleration of gastric emptying and colonic transit time in rats.

Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells.

PubMed

Kim, Dong Hwan; Sung, Bokyung; Kang, Yong Jung; Hwang, Seong Yeon; Kim, Min Jeong; Yoon, Jeong-Hyun; Im, Eunok; Kim, Nam Deuk

2015-12-01

The effects of sulforaphane (a natural product commonly found in broccoli) was investigated on hypoxia inducible factor-1α (HIF-1α) expression in HCT116 human colon cancer cells and AGS human gastric cancer cells. We found that hypoxia-induced HIF-1α protein expression in HCT116 and AGS cells, while treatment with sulforaphane markedly and concentration-dependently inhibited HIF-1α expression in both cell lines. Treatment with sulforaphane inhibited hypoxia-induced vascular endothelial growth factor (VEGF) expression in HCT116 cells. Treatment with sulforaphane modulated the effect of hypoxia on HIF-1α stability. However, degradation of HIF-1α by sulforaphane was not mediated through the 26S proteasome pathway. We also found that the inhibition of HIF-1α by sulforaphane was not mediated through AKT and extracellular signal-regulated kinase phosphorylation under hypoxic conditions. Finally, hypoxia-induced HCT116 cell migration was inhibited by sulforaphane. These data suggest that sulforaphane may inhibit human colon cancer progression and cancer cell angiogenesis by inhibiting HIF-1α and VEGF expression. Taken together, these results indicate that sulforaphane is a new and potent chemopreventive drug candidate for treating patients with human colon cancer.

Variable expression of molecular markers in juvenile nasopharyngeal angiofibroma.

PubMed

Mishra, A; Pandey, A; Mishra, S C

2017-09-01

Molecular categorisation may explain the wide variation in the clinical characteristics of juvenile nasopharyngeal angiofibroma. Variations in molecular markers in juvenile nasopharyngeal angiofibroma in an Indian population were investigated and compared with global reports. Variable molecular marker expression was demonstrated at the regional and global levels. A wide variation in molecular characteristics is evident. Molecular data have been reported for only 11 countries, indicating a clear geographical bias. Only 58 markers have been studied, and most are yet to be validated. Research into the molecular epidemiology of juvenile nasopharyngeal angiofibroma is still in its infancy. Although the molecular variation is not well understood, data obtained so far have prompted important research questions. Hence, multicentre collaborative molecular studies are needed to establish the aetiopathogenesis and establish molecular surrogates for clinical characteristics.

Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective.

PubMed

Lee, Anne W M; Ma, Brigette B Y; Ng, Wai Tong; Chan, Anthony T C

2015-10-10

Nasopharyngeal carcinoma of the undifferentiated subtype is endemic to southern China, and patient prognosis has improved significantly over the past three decades because of advances in disease management, diagnostic imaging, radiotherapy technology, and broader application of systemic therapy. Despite the excellent local control with modern radiotherapy, distant failure remains a key challenge. Advances in molecular technology have helped to decipher the molecular pathogenesis of nasopharyngeal carcinoma as well as its etiologic association with the Epstein-Barr virus. This in turn has led to the discovery of novel biomarkers and drug targets, rendering this cancer site a current focus for new drug development. This article reviews and appraises the key literature on the current management of nasopharyngeal carcinoma and future directions in clinical research. © 2015 by American Society of Clinical Oncology.

Houttuynia cordata Thunb extract induces cytotoxicity in human nasopharyngeal carcinoma cells: Raman spectroscopic studies

NASA Astrophysics Data System (ADS)

Chen, Weiwei; Li, Zuanfang; Yu, Yun; Lin, Duo; Huang, Hao; Shi, Hong

2016-01-01

The molecular mechanisms of cytotoxicity induced by Houttuynia cordata Thunb (HCT) in nasopharyngeal carcinoma (NPC) cells was investigated by Raman spectroscopy (RS). The average Raman spectra of cell groups treated with HCT (0, 62.5, 125, 250, and 500 μg ml-1) for 24 h were measured separately. Compared to the control group, the intensities of the selected bands (1002, 1338, and 1448 cm-1) related to protein, DNA, and lipid in the treatment groups decreased obviously as the concentration of HCT increased. Both cell groups treated with 250 and 500 μg ml-1 of HCT could be differentiated from the control group by principal component analysis (PCA) combined with linear discriminate analysis (LDA) with a diagnostic accuracy of 100%, suggesting that cytotoxicity occurred and that 250 μg ml-1 was the proper dose for treatment. Simultaneously, the Raman spectra of cells treated with different treatment times with 250 μg ml-1 of HCT were obtained. We can get that treatment with HCT decreased cell viability in a dose and time-dependent fashion. The results indicated that the RS combined with PCA-LDA can be used for pharmacokinetics studies of HCT in NPC cells, which could also provide useful data for clinical dosage optimization for HCT.

Probiotics reduce repeated water avoidance stress-induced colonic microinflammation in Wistar rats in a sex-specific manner

PubMed Central

Lee, Ju Yup; Nam, Ryoung Hee; Sohn, Sung Hwa; Lee, Sun Min; Choi, Daeun; Yoon, Hyuk; Kim, Yong Sung; Lee, Hye Seung; Lee, Dong Ho

2017-01-01

The colonic response to stress is greater in female rats than in male rats. The aim of this study was to evaluate the effect of probiotics in the repeated water avoidance stress (rWAS)-induced colonic microinflammation model of Wistar rats in a sex-specific manner. The three groups (no-stress, WAS, and WAS with probiotics) were exposed to r-WAS for 1 h daily for 10 days, and Lactobacillus farciminis was administered by oral gavage for 10 days to animals in the probiotics group. The visceromotor response (VMR) to colorectal distension (CRD) was assessed using a barostat and noninvasive manometry before and after WAS exposure. Immunohistochemistry for mast cells and real-time polymerase chain reaction (RT-PCR) for detection of mucosal cytokines were performed using distal colon tissue after the animals were sacrificed. Significant reduction of VMR to CRD (visceral analgesia) was observed at 60 mmHg in the female WAS group (P = 0.045), but not in males. In addition, the female WAS with probiotics group showed a significantly lower colonic mucosal mast cell count in comparison to the female WAS group (P = 0.013), but this phenomenon was not observed in the male group. The colonic mucosal mRNA levels of interferon-γ (IFNR), tumor necrosis factor-α (TNFA), interleukin (IL) 6, and IL17 were higher in the female WAS group than in the male WAS group. The mRNA levels of IFNR, TNFA, and IL6 were significantly decreased in WAS females who received probiotics (all P < 0.050). In conclusion, rWAS is induced in a sex-specific manner. A 10-day-long treatment with L. farciminis is an effective therapy for rWAS-induced colonic microinflammation in female rates, but not in male rats. PMID:29244820

Probiotics reduce repeated water avoidance stress-induced colonic microinflammation in Wistar rats in a sex-specific manner.

PubMed

Lee, Ju Yup; Kim, Nayoung; Nam, Ryoung Hee; Sohn, Sung Hwa; Lee, Sun Min; Choi, Daeun; Yoon, Hyuk; Kim, Yong Sung; Lee, Hye Seung; Lee, Dong Ho

2017-01-01

The colonic response to stress is greater in female rats than in male rats. The aim of this study was to evaluate the effect of probiotics in the repeated water avoidance stress (rWAS)-induced colonic microinflammation model of Wistar rats in a sex-specific manner. The three groups (no-stress, WAS, and WAS with probiotics) were exposed to r-WAS for 1 h daily for 10 days, and Lactobacillus farciminis was administered by oral gavage for 10 days to animals in the probiotics group. The visceromotor response (VMR) to colorectal distension (CRD) was assessed using a barostat and noninvasive manometry before and after WAS exposure. Immunohistochemistry for mast cells and real-time polymerase chain reaction (RT-PCR) for detection of mucosal cytokines were performed using distal colon tissue after the animals were sacrificed. Significant reduction of VMR to CRD (visceral analgesia) was observed at 60 mmHg in the female WAS group (P = 0.045), but not in males. In addition, the female WAS with probiotics group showed a significantly lower colonic mucosal mast cell count in comparison to the female WAS group (P = 0.013), but this phenomenon was not observed in the male group. The colonic mucosal mRNA levels of interferon-γ (IFNR), tumor necrosis factor-α (TNFA), interleukin (IL) 6, and IL17 were higher in the female WAS group than in the male WAS group. The mRNA levels of IFNR, TNFA, and IL6 were significantly decreased in WAS females who received probiotics (all P < 0.050). In conclusion, rWAS is induced in a sex-specific manner. A 10-day-long treatment with L. farciminis is an effective therapy for rWAS-induced colonic microinflammation in female rates, but not in male rats.

Differential diagnosis of primary nasopharyngeal lymphoma and nasopharyngeal carcinoma focusing on CT, MRI, and PET/CT.

PubMed

Cho, Kyu-Sup; Kang, Dae-Woon; Kim, Hak-Jin; Lee, Jong-Kil; Roh, Hwan-Jung

2012-04-01

No study has done a comparative analysis of radiologic imaging findings between primary nasopharyngeal lymphoma (PNL) and nasopharyngeal carcinoma (NPC). The purpose of this study was to analyze computed tomography (CT) and magnetic resonance (MR) images and to evaluate the maximum standardized uptake value (SUV max) of positron emission tomography (PET)/CT between PNL and NPC, knowing the imaging features that distinguish PNL from NPC. Cross-sectional study. University tertiary care facility. The authors analyzed the features on CT, MR imaging, and PET/CT of 16 patients diagnosed with PNL and 32 patients diagnosed with NPC histopathologically. Patients with PNL had a larger tumor volume and showed symmetry of tumor shape than did patients with NPC. Patients with PNL also had higher tumor homogeneity than NPC patients on CT, T2-weighted, and postcontrast MR images. All PNL patients showed a high degree of enhancement without invasion to the adjacent deep structure. The involvement of the Waldeyer ring was significantly higher in PNL patients. Cervical and retropharyngeal lymphadenopathy and PET/CT SUV max showed no significant difference between PNL and NPC. If the images present a bulky, symmetric nasopharyngeal mass with marked homogeneity, a high degree of enhancement, and a higher Waldeyer ring involvement combined with no invasion into the deep structure, PNL should be considered over NPC.

Detection of nasopharyngeal cancer using confocal Raman spectroscopy and genetic algorithm technique

NASA Astrophysics Data System (ADS)

Li, Shao-Xin; Chen, Qiu-Yan; Zhang, Yan-Jiao; Liu, Zhi-Ming; Xiong, Hong-Lian; Guo, Zhou-Yi; Mai, Hai-Qiang; Liu, Song-Hao

2012-12-01

Raman spectroscopy (RS) and a genetic algorithm (GA) were applied to distinguish nasopharyngeal cancer (NPC) from normal nasopharyngeal tissue. A total of 225 Raman spectra are acquired from 120 tissue sites of 63 nasopharyngeal patients, 56 Raman spectra from normal tissue and 169 Raman spectra from NPC tissue. The GA integrated with linear discriminant analysis (LDA) is developed to differentiate NPC and normal tissue according to spectral variables in the selected regions of 792-805, 867-880, 996-1009, 1086-1099, 1288-1304, 1663-1670, and 1742-1752 cm-1 related to proteins, nucleic acids and lipids of tissue. The GA-LDA algorithms with the leave-one-out cross-validation method provide a sensitivity of 69.2% and specificity of 100%. The results are better than that of principal component analysis which is applied to the same Raman dataset of nasopharyngeal tissue with a sensitivity of 63.3% and specificity of 94.6%. This demonstrates that Raman spectroscopy associated with GA-LDA diagnostic algorithm has enormous potential to detect and diagnose nasopharyngeal cancer.

Properties of acetylcholine-induced relaxation of smooth muscle isolated from the proximal colon of the guinea-pig.

PubMed

Kodama, Youhei; Iino, Satoshi; Shigemasa, Yuhsuke; Suzuki, Hikaru

2010-01-01

The properties of mechanical responses elicited by stimulation with acetylcholine (ACh) were investigated in circular smooth muscle preparations isolated from the proximal colon of guinea-pig. Application of ACh (10(-8)-10(-6) M) for 3-5 min produced a biphasic response, with an initial contraction followed by a relaxation. Atropine inhibited the initial contraction, while N(ω)-nitro-L-arginine (L-NA) inhibited the relaxation, suggesting that the former was produced by activation of muscarinic receptors while the latter was produced by an elevated production of nitric oxide (NO). In the presence of atropine, the ACh-relaxation was attenuated by removal of the mucosa and abolished by removal of both submucosal and mucosal layers. The ACh-induced relaxation was also attenuated by either tetrodotoxin (TTX, 3 × 10(-7) M) or hexamethonium (10(-6) M). In the presence of atropine, transmural nerve stimulation (TNS) elicited a biphasic response, with an initial phasic contraction followed by a relaxation. The amplitude of TNS-induced relaxation was significantly reduced by hexamethonium or L-NA and was abolished by TTX. Both ACh and TNS produced relaxation in preparations isolated from the proximal colon, but not in those from the middle part of colon. Immunohistochemistry for neuronal nitric oxide synthase revealed no difference in the distribution of nitrergic nerves between the proximal and middle part of the colon, with nitrergic nerves in both the mucosal and submucosal layers as well as in the smooth muscle and myenteric layers. These results suggest that ACh induces NO production by excitation of postganglionic nerves distributed mainly in the mucosal and submucosal layers. In circular smooth muscle preparations isolated from the middle part of colon, ACh or TNS produced contractile responses alone, with no associated relaxation, suggesting that the ACh-activated postganglionic nitrergic nerves are distributed in the mucosal and submucosal layers of the proximal

Effect of royal jelly on experimental colitis induced by acetic acid and alteration of mast cell distribution in the colon of rats

PubMed Central

Karaca, T.; Bayiroglu, F.; Yoruk, M.; Kaya, M.S.; Uslu, S.; Comba, B.; Mis, L.

2010-01-01

This study investigated the effects of royal jelly (RJ) on acetic acid-induced colitis in rats. Twenty adult female Wistar albino rats were divided into four treatment groups of 5 animals each, including a control group (Group I); Group II was treated orally with RJ (150 mg kg−1 body weight); Group III had acetic acid-induced colitis; and Group IV had acetic acid-induced colitis treated orally with RJ (150 mg kg−1 body weight) for 4 weeks. Colitis was induced by intracolonic instillation of 4% acetic acid; the control group received physiological saline (10 mL kg−1). Colon samples were obtained under deep anaesthesia from animals in all groups. Tissues were fixed in 10% formalin neutral buffer solution for 24 h and embedded in paraffin. Six-micrometre-thick sections were stained with Mallory’s triple stain and toluidine blue in 1% aqueous solution at pH 1.0 for 5 min (for Mast Cells). RJ was shown to protect the colonic mucosa against the injurious effect of acetic acid. Colitis (colonic damage) was confirmed histomorphometrically as significant increases in the number of mast cells (MC) and colonic erosions in rats with acetic acid-induced colitis. The RJ treatment significantly decreased the number of MC and reduced the area of colonic erosion in the colon of RJ-treated rats compared with rats with untreated colitis. The results suggest that oral treatment with RJ could be used to treat colitis. PMID:21263740

Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport

PubMed Central

Sayer, Brooke; Lu, Jun; Green, Christina; Söderholm, Johan D; Akhtar, Mahmood; McKay, Derek M

2002-01-01

Neuronal cholinergic input is an important regulator of epithelial electrolyte transport and hence water movement in the gut. In this study, colitis was induced by treating mice with 4% (w v−1) dextran sodium-sulphate (DSS)-water for 5 days followed by 3 days of normal water. Mid-colonic segments were mounted in Ussing chambers and short-circuit current (Isc, indicates net ion movement) responses to the cholinergic agonist, carbachol (CCh; 10−4 M)±tetrodotoxin, atropine (ATR), hexamethonium (HEX), naloxone or phenoxybenzamine were assessed. Tissues from mice with DSS-induced colitis displayed a drop in Isc in response to CCh (−11.3±3.3 μA/cm2), while those from control mice showed a transient increase in Isc (76.3±13.0 μA/cm2). The ΔIsc in colon from DSS-treated mice was tetrodotoxin-sensitive, atropine-insensitive and was reversed by hexamethonium (HEX+CCh=16.7±7.8 μA/cm2), indicating involvement of a nicotinic receptor. CCh induced a drop in Isc in tissues from controls only when they were pretreated with the cholinergic muscarinic receptor blocker, atropine: ATR+CCh=−21.3±7.0 μA/cm2. Nicotine elicited a drop in Isc in Ussing-chambered colon from both control and DSS-treated mice that was TTX-sensitive. The drop in Isc evoked by CCh challenge of colonic tissue from DSS-treated mice or ATR+CCh challenge of control tissue was not significantly affected by blockade of opiate or α-adrenergic receptors by naloxone or phenoxybenzamine, respectively. The data indicate that DSS-colitis reveals a nicotinic receptor that becomes important in cholinergic regulation of ion transport. PMID:11934821

Sambar, an Indian Dish Prevents the Development of Dimethyl Hydrazine–Induced Colon Cancer: A Preclinical Study

PubMed Central

Prasad, Vutturu Ganga; Reddy, Neetinkumar; Francis, Albi; Nayak, Pawan G.; Kishore, Anoop; Nandakumar, Krishnadas; Rao, Mallikarjuna C.; Shenoy, Rekha

2016-01-01

Background: Colon cancer (CC) is the third commonly diagnosed cancer and the second leading cause of mortality in the US when compared to India where prevalence is less. Possible reason could be the vegetarian diet comprising spices used in curry powders. Researchers believe that 70% of the cases are associated with diet. Spices have inherited a rich tradition for their flavor and medicinal properties. Researchers have been oriented towards spices present in food items for their antitumorigenic properties. Objective: We investigated the effects of sambar as a preventive measure for 1,2-dimethyl hydrazine (DMH)-induced CC in Wistar albino rats. Materials and Methods: The animals were divided into three groups (n = 6) namely control, DMH, and sambar. At the end of the experimental period, the animals were killed using anesthesia and the colons and livers were examined. Results: All the treatment groups exhibited a significant change in the number of aberrant crypt foci (ACF). Sambar group showed a significant change in the colonic GSH when compared to both normal and DMH groups. A significant reduction in the liver GSH was noted in the sambar group. Only sambar group showed a significant change in the liver catalase levels when compared to DMH. There was a significant reduction in the colonic nitrite in the sambar-treated group; 2.94 ± 0.29 when compared to DMH control at 8.09 ± 1.32. On the contrary, a significant rise in the liver nitrite levels was observed in the sambar-treated rats. Conclusion: Sambar may prevent the risk of CC when consumed in dietary proportions. SUMMARY Consumption of sambar significantly reduced aberrant crypt foci in DMH-induced colon cancer modelSambar treatment prevented DMH-induced oxidative changes in the colonic tissue, indicating its antioxidant roleSambar comprises a variety of spices that exhibited both pro- and antioxidant properties in different tissues, leading to its overall beneficial effect in this model. Abbreviations used

[6]-gingerol induces electrogenic sodium absorption in the rat colon via the capsaicin receptor TRPV1.

PubMed

Tsuchiya, Yo; Fujita, Rina; Saitou, Akae; Wajima, Nanako; Aizawa, Fuyuka; Iinuma, Akane

2014-01-01

[6]-Gingerol possesses a variety of beneficial pharmacological and therapeutic properties, including anti-carcinogenic, anti-inflammatory, and anti-emetic activities. Although [6]-gingerol is known to regulate the contraction of the intestine, its effect on intestinal ion transport is unclear. The aim of this study was to examine the role of [6]-gingerol in the regulation of electrogenic ion transport in the rat intestine by measuring the transmural potential difference (ΔPD). [6]-Gingerol induced significant positive ΔPD when administered to the serosal but not mucosal side of the colon, ileum, and jejunum; the highest effect was detected in the colon at a concentration of 10 μM. [6]-Gingerol-induced increase in ΔPD was suppressed by ouabain, an inhibitor of Na(+)/K(+)-ATPase, whereas no effect was observed in response to bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) co-transporter. In addition, ΔPD induction by [6]-gingerol was greatly diminished by capsazepine, an inhibitor of the capsaicin receptor TRPV1. These results suggest that [6]-gingerol induced the electrogenic absorption of sodium in the rat colon via TRPV1.

Salvia miltiorrhiza (dan shen) significantly ameliorates colon inflammation in dextran sulfate sodium induced colitis.

PubMed

Wen, Xiao-Dong; Wang, Chong-Zhi; Yu, Chunhao; Zhang, Zhiyu; Calway, Tyler; Wang, Yunwei; Li, Ping; Yuan, Chun-Su

2013-01-01

Inflammatory bowel disease increases the risks of human colorectal cancer. In this study, the effects of Salvia miltiorrhiza extract (SME) on chemically-induced colitis in a mouse model were evaluated. Chemical composition of SME was determined by HPLC analysis. A/J mice received a single injection of AOM 7.5 mg/kg. After one week, these mice received 2.5% DSS for eight days, or DSS plus SME (25 or 50 mg/kg). DSS-induced colitis was scored with the disease activity index (DAI). Body weight and colon length were also measured. The severity of inflammatory lesions was further evaluated by colon tissue histological assessment. HPLC assay showed that the major constituents in the tested SME were danshensu, protocatechuic aldehyde, salvianolic acid D, and salvianolic acid B. In the model group, the DAI score reached its highest level on Day 8, while the SME group on both doses showed a significantly reduced DAI score (both p < 0.01). As an objective index of the severity of inflammation, colon length was significantly shorter in the model group than the vehicle group. Treatment with 25 and 50 mg/kg of SME inhibited the shortening of colon in a dose-related manner (p < 0.05 and p < 0.01, respectively). SME groups also significantly reduced weight reduction (p < 0.05). Colitis histological data supported the pharmacological observations. Thus, Salvia miltiorrhiza could be a promising candidate in preventing and treating colitis and in reducing the risks of inflammation-associated colorectal cancer.

[Inhibitive effect of matrine modification X on the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice].

PubMed

Shi, Shujing; Tang, Anzhou; Yin, Shaolin; Wang, Lisheng; Xie, Mao; Yi, Xiang

2014-11-01

To evaluate the inhibitive effect of matrine modification X on the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice. Tumor model was established by subcutaneous inoculation of nasopharyngeal carcinoma cell CNE2 into nude mice, which was used to evaluate the antitumor effect of matrine modification X in vivo. The expression levels of Bax, Bcl-2, Caspase3 were detected by real-time PCR and western blot. The growth of xenografts in nude mice was significantly suppressed after application of matrine modification X in a dose-dependent manner. The inhibition rates were 32.55% and 44.89% when treated at medium and high dose respectively. Real-time fluorescence quantitative-PCR and Western Blot results showed that the expression of Bax and Caspase3 increased, while the expression of Bcl-2 decreased in a dose-dependent manner. The change of high dose group was obvious, and the difference was statistically significant (P < 0.05). Matrine modification X could significantly inhibit the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice, probably by inducing the apoptosis of nasopharyngeal carcinoma cells, and the possible mechanism is related to regulating the expression level of Bax/Bcl-2 and Casepase3.

Radiation-Induced Cranial Nerve Palsy: A Cross-Sectional Study of Nasopharyngeal Cancer Patients After Definitive Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Lin, E-mail: konglinj@gmail.co; Lu, Jiade J.; Department of Radiation Oncology, National University Cancer Institute of Singapore

2011-04-01

Purpose: To address the characteristics and the causative factors of radiation-induced cranial nerve palsy (CNP) in nasopharyngeal carcinoma (NPC) patients with an extensive period of followed-up. Patients and Methods: A total of 317 consecutive and nonselected patients treated with definitive external-beam radiotherapy between November 1962 and February 1995 participated in this study. The median doses to the nasopharynx and upper neck were 71 Gy (range, 55-86 Gy) and 61 Gy (range, 34-72 Gy), respectively. Conventional fractionation was used in 287 patients (90.5%). Forty-five patients (14.2%) received chemotherapy. Results: The median follow-up was 11.4 years (range, 5.1-38.0 years). Ninety-eight patients (30.9%)more » developed CNP, with a median latent period of 7.6 years (range, 0.3-34 years). Patients had a higher rate of CNP (81 cases, 25.5%) in lower-group cranial nerves compared with upper group (44 cases, 13.9%) ({chi}{sup 2} = 34.444, p < 0.001). Fifty-nine cases experienced CNP in more than one cranial nerve. Twenty-two of 27 cases (68.8%) of intragroup CNP and 11 of 32 cases (40.7%) of intergroup CNP occurred synchronously ({chi}{sup 2} = 4.661, p = 0.031). The cumulative incidences of CNP were 10.4%, 22.4%, 35.5%, and 44.5% at 5, 10, 15, and 20 years, respectively. Multivariate analyses revealed that CNP at diagnosis, chemotherapy, total radiation dose to the nasopharynx, and upper neck fibrosis were independent risk factors for developing radiation-induced CNP. Conclusion: Radiation-induced fibrosis may play an important role in radiation-induced CNP. The incidence of CNP after definitive radiotherapy for NPC remains high after long-term follow-up and is dose and fractionation dependent.« less

Wogonin induces cross-regulation between autophagy and apoptosis via a variety of Akt pathway in human nasopharyngeal carcinoma cells.

PubMed

Chow, Shu-Er; Chen, Yu-Wen; Liang, Chi-Ang; Huang, Yao-Kuan; Wang, Jong-Shyan

2012-11-01

Autophagy as well as apoptosis is an emerging target for cancer therapy. Wogonin, a flavonoid compound derived from the traditional Chinese medicine of Huang-Qin, has anticancer activity in many cancer cells including human nasopharyngeal carcinoma (NPC). However, the involvement of autophagy in the wogonin-induced apoptosis of NPC cells was still uninvestigated. In this study, we found wogonin-induced autophagy had interference on the process of apoptosis. Wogonin-induced autophagy formation evidenced by LC3 I/II cleavage, acridine orange (AO)-stained vacuoles and the autophagosome/autolysosome images of TEM analysis. Activation of autophagy with rapamycin resulted in increased wogonin-mediated autophagy via inhibition of mTOR/P70S6K pathway. The functional relevance of autophagy in the antitumor activity was investigated by annexin V-positive stained cells and PARP cleavage. Induction of autophagy by rapamycin ameliorated the wogonin-mediated apoptosis, whereas inhibition of autophagy by 3-methyladenine (3-MA) or bafilomycin A1 increased the apoptotic effect. Interestingly, this study also found, in addition the mTOR/P70S6K pathway, wogonin also inhibited Raf/ERK pathway, a variety of Akt pathways. Inactivation of PI(3) K/Akt by their inhibitors significantly induced apoptosis and markedly sensitized the NPC cells to wogonin-induced apoptosis. This anticancer effect of Akt was further confirmed by SH6, a specific inhibitor of Akt. Importantly, inactivation of its downstream molecule ERK by PD98059, a MEK inhibitor, also induced apoptosis. This study indicated wogonin-induced both autophagy and apoptosis through a variety of Akt pathways and suggested modulation of autophagy might provide profoundly the potential therapeutic effect. Copyright © 2012 Wiley Periodicals, Inc.

Using Bayesian modelling to investigate factors governing antibiotic-induced Candida albicans colonization of the GI tract

PubMed Central

Shankar, Jyoti; Solis, Norma V.; Mounaud, Stephanie; Szpakowski, Sebastian; Liu, Hong; Losada, Liliana; Nierman, William C.; Filler, Scott G.

2015-01-01

Receipt of broad-spectrum antibiotics enhances Candida albicans colonization of the GI tract, a risk factor for haematogenously-disseminated candidiasis. To understand how antibiotics influence C. albicans colonization, we treated mice orally with vancomycin or a combination of penicillin, streptomycin, and gentamicin (PSG) and then inoculated them with C. albicans by gavage. Only PSG treatment resulted in sustained, high-level GI colonization with C. albicans. Furthermore, PSG reduced bacterial diversity in the colon much more than vancomycin. Both antibiotic regimens significantly reduced IL-17A, IL-21, IL-22 and IFN-γ mRNA levels in the terminal ileum but had limited effect on the GI fungal microbiome. Through a series of models that employed Bayesian model averaging, we investigated the associations between antibiotic treatment, GI microbiota, and host immune response and their collective impact on C. albicans colonization. Our analysis revealed that bacterial genera were typically associated with either C. albicans colonization or altered cytokine expression but not with both. The only exception was Veillonella, which was associated with both increased C. albicans colonization and reduced IL-21 expression. Overall, antibiotic-induced changes in the bacterial microbiome were much more consistent determinants of C. albicans colonization than either the GI fungal microbiota or the GI immune response. PMID:25644850

Membrane-type matrix metalloproteinases mediate curcumin-induced cell migration in non-tumorigenic colon epithelial cells differing in Apc genotype.

PubMed

Fenton, Jenifer I; Wolff, Margaret S; Orth, Michael W; Hord, Norman G

2002-06-01

Colonic epithelial cell migration is required for normal differentiated cell function. This migratory phenotype is dependent upon wild-type adenomatous polyposis coli (Apc) expression. Non-tumorigenic murine colon epithelial cell lines with distinct Apc genotypes, i.e. young adult mouse colon (YAMC; Apc(+/+)) and immortomouse/Min colon epithelial (IMCE; Apc(Min/+) cells) were used to assess the association between the Apc genotype, cell motility and matrix metalloproteinase (MMP) activity. Cells were treated with epidermal growth factor (EGF; 1, 10 and 25 ng/ml), hepatocyte growth factor (HGF; 1, 10 and 25 ng/ml) and/or curcumin (0.1-100 microM). EGF (25 ng/ml) and HGF (25 ng/ml) induced a greater migratory response in YAMC compared with IMCE cells after 24 h (P < 0.05). Treatment with curcumin induced a greater or equivalent migratory response in IMCE than YAMC cells. When migrating cells were treated with Ilomastat (MMP inhibitor), migration was inhibited in both cell types. High concentrations of Ilomastat (25 and 50 microM) inhibited migration in both cell types, while low concentrations (10 microM) inhibited HGF-induced IMCE migration. Curcumin-induced migration was inhibited in both cell types at the highest concentration of Ilomastat (50 microM). Immuno-localization analysis of membrane type-1 (MT1)-MMP indicated that migration is associated with the redistribution of this protein from the endoplasmic reticulum to the plasma membrane. Addition of neutralizing polyclonal antibodies against MT1-MMP or a mixture of MT1, 2- and 3-MMPs demonstrated partial or complete inhibition of cell migration in both cell types, respectively. The data provide the first evidence that migration in non-tumorigenic murine colon epithelial cells is: (i) inducible by EGF and HGF in an Apc genotype-dependent manner, (ii) dependent on MT-MMP activity and (iii) inducible by curcumin in an Apc genotype-independent manner. The data suggest a potential mechanism by which curcumin may

Impact of amoxicillin on pneumococcal colonization compared with other therapies for acute otitis media.

PubMed

Toltzis, Philip; Dul, Michael; O'Riordan, Mary Ann; Toltzis, Hasida; Blumer, Jeffrey L

2005-01-01

This study compared the effects of 4 outpatient antibiotic regimens on colonization by penicillin-susceptible and -nonsusceptible pneumococci to assess their relative potential to promote colonization with Streptococcus pneumoniae with reduced susceptibility to penicillin. Children presenting with acute otitis media were randomized to receive amoxicillin, cefprozil, ceftriaxone or azithromycin. Nasopharyngeal specimens were collected on days 0, 3-5, 10-14 and 28-30 and assessed for the presence of S. pneumoniae. At each visit, the proportions of penicillin-susceptible and -nonsusceptible pneumococci were compared among treatment groups. Among 1009 enrollees, the prevalence of colonization by S. pneumoniae at baseline was 23.5%, of which 41.1% were penicillin-nonsusceptible. Colonization by nonsusceptible pneumococci was unaltered during the observation period in all treatment groups, with no detectable differences among groups at each visit. By contrast, there was a substantial reduction in the prevalence of colonization by penicillin-susceptible organisms, most notably in subjects treated with amoxicillin. This resulted in a proportional shift toward resistant organism colonization in all groups, with this shift being significantly more pronounced among amoxicillin recipients than in the other groups at 10-12 days (P < 0.02 for each comparison with amoxicillin). Treatment with amoxicillin for acute otitis media resulted in a larger shift toward nonsusceptible organism colonization among those children still colonized postexposure than did treatment with 3 comparison agents. This phenomenon raises theoretical concerns that at the population level, amoxicillin produces conditions that promote the dissemination of the nonsusceptible phenotype more readily than other outpatient antibiotics. Confirmation of these results requires further study.

[ABOUT JUVENILE NASOPHARYNGEAL ANGIOFIBROMA].

PubMed

Urbain, V; Meunier, P; Otto, B

2015-09-01

We report the case of a young man with a juvenile nasopharyngeal angiofibroma. In this paper, we will first remind the clinical signs of this pathology and its radiological appearance (localisation and extensions). Then we will explain how radioembolisation techniques were used to facilitate the surgical intervention. Finally we will discuss the histology of this tumor.

Involvement of AMPK signaling cascade in capsaicin-induced apoptosis of HT-29 colon cancer cells.

PubMed

Kim, Young Min; Hwang, Jin-Taek; Kwak, Dong Wook; Lee, Yun Kyung; Park, Ock Jin

2007-01-01

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is activated during ATP-depleting metabolic states, such as hypoxia, heat shock, oxidative stress, and exercise. As a highly conserved heterotrimeric kinase that functions as a major metabolic switch to maintain energy homeostasis, AMPK has been shown to exert as an intrinsic regulator of mammalian cell cycle. Moreover, AMPK cascade has emerged as an important pathway implicated in cancer control. In this article, we have investigated the effects of capsaicin on apoptosis in relation to AMPK activation in colon cancer cell. Capsaicin-induced apoptosis was revealed by the presence of nucleobodies in the capsaicin-treated HT-29 colon cancer cells. Concomitantly, the activation of AMPK and the increased expression of the inactive form of acetyl-CoA carboxylase (ACC) were detected in capsaicin-treated colon cancer cells. We showed that both capsaicin and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR), an AMPK activator possess the AMPK-activating capacity as well as apoptosis-inducing properties. Evidence of the association between AMPK activation and the increased apoptosis in HT-29 colon cancer cells by capsaicin treatment, and further findings of the correlation of the activated AMPK and the elevated apoptosis by cotreatment of AICAR and capsaicin support AMPK as an important component of apoptosis, as well as a possible target of cancer control.

Nasopharyngeal tuberculosis presenting as massive cervical lymphadenopathy and hearing loss.

PubMed

Özcan, Cengiz; Vaysoğlu, Yusuf; Güçlütürk, Taylan; Apa, Duygu Düşmez; Görür, Kemal

2012-07-01

Lymphadenitis is the most common form of tuberculosis in the head and neck region, but it can be seen in the other areas of the head and neck. Nasopharyngeal tuberculosis is a rare condition without pulmonary and systemic involvement. The majority of patients present with neck mass. A 17-year-old female patient admitted to our outpatient clinic with the complaints of swelling on both sides of the neck and hearing loss. The endoscopic examination revealed a nasopharyngeal mass, and biopsies were taken from the mass. The result of pathologic examination was reported as caseating granulomatous inflammation compatible with tuberculosis. In this report, a nasopharyngeal tuberculosis case associated with massive cervical lymphadenopathy was reported, and etiopathogenesis and treatment were also discussed.

Autophagy inhibition sensitizes WYE-354-induced anti-colon cancer activity in vitro and in vivo.

PubMed

Wang, Lijun; Zhu, Yun-Rong; Wang, Shaowei; Zhao, Song

2016-09-01

Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 are frequently dysregulated in human colon cancers. In the present study, we evaluated the potential anti-colon cancer cell activity by a novel mTORC1/2 dual inhibitor WYE-354. We showed that WYE-354 was anti-survival and anti-proliferative when adding to primary (patient-derived) and established (HCT-116, HT-29, Caco-2, LoVo, and DLD-1 lines) colon cancer cells. In addition, WYE-354 treatment activated caspase-dependent apoptosis in the colon cancer cells. Mechanistically, WYE-354 blocked mTORC1 and mTORC2 activation. Meanwhile, it also induced autophagy activation in the colon cancer cells. Autophagy inhibitors (bafilomycin A1 and 3-methyladenine), or shRNA-mediated knockdown of autophagy elements (Beclin-1 and ATG-5), remarkably sensitized WYE-354-mediated anti-colon cancer cell activity in vitro. Further studies showed that WYE-354 administration inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Importantly, its activity in vivo was further potentiated with co-administration of the autophagy inhibitor 3-MA. Phosphorylations of Akt (Ser-473) and S6 were also decreased in WYE-354-treated HT-29 xenografts. Together, these pre-clinical results demonstrate the potent anti-colon cancer cell activity by WYE-354, and its activity may be further augmented with autophagy inhibition.

The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity.

PubMed

Gentile, Daniela; Fornai, Matteo; Colucci, Rocchina; Pellegrini, Carolina; Tirotta, Erika; Benvenuti, Laura; Segnani, Cristina; Ippolito, Chiara; Duranti, Emiliano; Virdis, Agostino; Carpi, Sara; Nieri, Paola; Németh, Zoltán H; Pistelli, Laura; Bernardini, Nunzia; Blandizzi, Corrado; Antonioli, Luca

2018-01-01

Apigenin can exert beneficial actions in the prevention of obesity. However, its putative action on obesity-associated bowel motor dysfunctions is unknown. This study examined the effects of apigenin on colonic inflammatory and motor abnormalities in a mouse model of diet-induced obesity. Male C57BL/6J mice were fed with standard diet (SD) or high-fat diet (HFD). SD or HFD mice were treated with apigenin (10 mg/Kg/day). After 8 weeks, body and epididymal fat weight, as well as cholesterol, triglycerides and glucose levels were evaluated. Malondialdehyde (MDA), IL-1β and IL-6 levels, and let-7f expression were also examined. Colonic infiltration by eosinophils, as well as substance P (SP) and inducible nitric oxide synthase (iNOS) expressions were evaluated. Motor responses elicited under blockade of NOS and tachykininergic contractions were recorded in vitro from colonic longitudinal muscle preparations. When compared to SD mice, HFD animals displayed increased body weight, epididymal fat weight and metabolic indexes. HFD mice showed increments in colonic MDA, IL-1β and IL-6 levels, as well as a decrease in let-7f expression in both colonic and epididymal tissues. HFD mice displayed an increase in colonic eosinophil infiltration. Immunohistochemistry revealed an increase in SP and iNOS expression in myenteric ganglia of HFD mice. In preparations from HFD mice, electrically evoked contractions upon NOS blockade or mediated by tachykininergic stimulation were enhanced. In HFD mice, Apigenin counteracted the increase in body and epididymal fat weight, as well as the alterations of metabolic indexes. Apigenin reduced also MDA, IL-1β and IL-6 colonic levels as well as eosinophil infiltration, SP and iNOS expression, along with a normalization of electrically evoked tachykininergic and nitrergic contractions. In addition, apigenin normalized let-7f expression in epididymal fat tissues, but not in colonic specimens. Apigenin prevents systemic metabolic alterations

Primary Nasopharyngeal Tuberculosis Combined with Tuberculous Otomastoiditis and Facial Nerve Palsy

PubMed Central

Choi, Hee Young; Jang, Ji Hye; Lee, Kyung Mi; Choi, Woo Suk; Kim, Sang Hoon; Yeo, Seung Geun; Kim, Eui Jong

2016-01-01

Primary nasopharyngeal tuberculosis (TB) without pulmonary involvement is rare, even in endemic areas. Herein, we present a rare complication of primary nasopharyngeal TB accompanied with tuberculous otomastoiditis (TOM) and ipsilateral facial nerve palsy, in a 24-year-old female patient, with computed tomography and magnetic resonance imagery findings. PMID:27127580

Salvia miltiorrhiza (Dan Shen) Significantly Ameliorates Colon Inflammation in Dextran Sulfate Sodium Induced Colitis

PubMed Central

Wen, Xiao-Dong; Wang, Chong-Zhi; Yu, Chunhao; Zhang, Zhiyu; Calway, Tyler; Wang, Yunwei; Li, Ping; Yuan, Chun-Su

2014-01-01

Inflammatory bowel disease increases the risks of human colorectal cancer. In this study, the effects of Salvia miltiorrhiza extract (SME) on chemically-induced colitis in a mouse model were evaluated. Chemical composition of SME was determined by HPLC analysis. A/J mice received a single injection of AOM 7.5 mg/kg. After one week, these mice received 2.5% DSS for 8 days, or DSS plus SME (25 or 50 mg/kg). DSS-induced colitis was scored with the disease activity index (DAI). Body weight and colon length were also measured. The severity of inflammatory lesions was further evaluated by colon tissue histological assessment. HPLC assay showed that the major constituents in the tested SME were danshensu, protocatechuic aldehyde, salvianolic acid D and salvianolic acid B. In the model group, the DAI score reached its highest level on Day 8, while the SME group on both doses showed a significantly reduced DAI score (both P < 0.01). As an objective index of the severity of inflammation, colon length was reduced significantly from the vehicle group to model group. Treatment with 25 and 50 mg/kg of SME inhibited the reduction of colon in a dose-related manner (P < 0.05 and P < 0.01, respectively). SME groups also significantly reduced weight reduction (P < 0.05). Colitis histological data supported the pharmacological observations. Thus, Salvia miltiorrhiza could be a promising candidate in preventing and treating colitis and in reducing the risks of inflammation-associated colorectal cancer. PMID:24117071

A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis.

PubMed

Li, Ning; Feng, Lin; Han, Hui-Qiong; Yuan, Jing; Qi, Xue-Kang; Lian, Yi-Fan; Kuang, Bo-Hua; Zhang, Yu-Chen; Deng, Cheng-Cheng; Zhang, Hao-Jiong; Yao, You-Yuan; Xu, Miao; He, Gui-Ping; Zhao, Bing-Chun; Gao, Ling; Feng, Qi-Sheng; Chen, Li-Zhen; Yang, Lu; Yang, Dajun; Zeng, Yi-Xin

2016-10-10

Despite advances in the development of radiation against nasopharyngeal carcinoma (NPC), the management of advanced NPC remains a challenge. Smac mimetics are designed to neutralize inhibitor of apoptosis (IAP) proteins, thus reactivating the apoptotic program in cancer cells. In this study, we investigated the effect of a novel bivalent Smac mimetic APG-1387 in NPC. In vitro, APG-1387 in combination with TNF-α potently decreased NPC cell viability by inducing apoptosis in majority of NPC cell lines. The in vitro antitumor effect was RIPK1-dependent, whereas it was independent on IAPs, USP11, or EBV. Of note, the inhibition of NF-κB or AKT pathway rendered resistant NPC cells responsive to the treatment of APG-1387/TNF-α. In vivo, APG-1387 displayed antitumor activity as a single agent at well-tolerated doses, even in an in vitro resistant cell line. In summary, our results demonstrate that APG-1387 exerts a potent antitumor effect on NPC. These findings support clinical evaluation of APG-1387 as a potential treatment for advanced NPC. Copyright © 2016. Published by Elsevier Ireland Ltd.

Pre-treatment with Bifidobacterium breve UCC2003 modulates Citrobacter rodentium-induced colonic inflammation and organ specificity.

PubMed

Collins, James W; Akin, Ali R; Kosta, Artemis; Zhang, Ning; Tangney, Mark; Francis, Kevin P; Frankel, Gad

2012-11-01

Citrobacter rodentium, which colonizes the gut mucosa via formation of attaching and effacing (A/E) lesions, causes transmissible colonic hyperplasia. The aim of this study was to evaluate whether prophylactic treatment with Bifidobacterium breve UCC2003 can improve the outcome of C. rodentium infection. Six-week-old albino C57BL/6 mice were pre-treated for 3 days with B. breve, challenged with bioluminescent C. rodentium and administered B. breve or PBS-C for 8 days post-infection; control mice were either administered B. breve and mock-infected with PBS, or mock-treated with PBS-C and mock-infected with PBS. C. rodentium colonization was monitored by bacterial enumeration from faeces and by a combination of both 2D bioluminescence imaging (BLI) and composite 3D diffuse light imaging tomography with µCT imaging (DLIT-µCT). At day 8 post-infection, colons were removed and assessed for crypt hyperplasia, histology by light microscopy, bacterial colonization by immunofluorescence, and A/E lesion formation by electron microscopy. Prophylactic administration of B. breve did not prevent C. rodentium colonization or A/E lesion formation. However, this treatment did alter C. rodentium distribution within the large intestine and significantly reduced colonic crypt hyperplasia at the peak of bacterial infection. These results show that B. breve could not competitively exclude C. rodentium, but reduced pathogen-induced colonic inflammation.

Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vendramini-Costa, Débora Barbosa, E-mail: vendrami

Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and preventive agents and the racemic form of the styryl-lactone goniothalamin (GTN) has been shown to be a promising antiproliferative agent, with gastroprotective, antinociceptive and anti-inflammatory effects. As inflammation is a well-known tumor promoter, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTNmore » on chemically induced and spontaneous colitis, as well as the cytotoxic effects of GTN on a human colon tumor cell line (HT-29). GTN treatments inhibited TNBS-induced acute and chronic colitis development in Wistar rats, reducing myeloperoxidase levels and inflammatory cells infiltration in the mucosa. In spontaneous-colitis using IL-10 deficient mice (C57BL/6 background), GTN prevented colitis development through downregulation of TNF-α, upregulation of SIRT-1 and inhibition of proliferation (PCNA index), without signs of toxicity after three months of treatment. In HT-29 cells, treatment with 10 μM of GTN induced apoptosis by increasing BAX/BCL2, p-JNK1/JNK1, p-P38/P38 ratios as well as through ROS generation. Caspase 8, 9 and 3 activation also occurred, suggesting caspase-dependent apoptotic pathway, culminating in PARP-1 cleavage. Together with previous data, these results show the importance of GTN as a pro-apoptotic, preventive and therapeutic agent for IBD and highlight its potential as a chemopreventive agent for colon cancer. - Highlights: • Goniothalamin (GTN) inhibits the development of TNBS-induced colitis in rats. • Moreover, GTN prevents the development of spontaneous colitis in IL-10 deficient mice. • This activity relies on downregulation of TNF-α and upregulation of SIRT-1

Inactivation of parkin by promoter methylation correlated with lymph node metastasis and genomic instability in nasopharyngeal carcinoma.

PubMed

Ni, Haifeng; Zhou, Zhen; Jiang, Bo; Yuan, Xiaoyang; Cao, Xiaolin; Huang, Guangwu; Li, Yong

2017-03-01

This study aimed to investigate the inactivation of the parkin gene by promoter methylation and its relationship with genome instability in nasopharyngeal carcinoma. Parkin was considered as a tumor suppressor gene in various types of cancers. However, its role in nasopharyngeal carcinoma is unexplored. Genomic instabilities were detected in nasopharyngeal carcinoma tissues by the random amplified polymorphic DNA. The methylation-specific polymerase chain reaction, semi-quantitative reverse transcription polymerase chain reaction, and immunohistochemical analysis were used to detect methylation and mRNA and protein expression of parkin in 54 cases of nasopharyngeal carcinoma tissues and 16 cases of normal nasopharyngeal epithelia tissues, and in 5 nasopharyngeal carcinoma cell lines (CNE1, CNE2, TWO3, C666, and HONE1) and 1 normal nasopharyngeal epithelia cell line (NP69). mRNA expression of parkin in CNE1 and CNE2 was analyzed before and after methyltransferase inhibitor 5-aza-2-deoxycytidine treatment. The relationship between promoter methylation and mRNA expression, demethylation and mRNA expression, and mRNA and protein expression of the gene and clinical factors and genomic instabilities were analyzed. The mRNA and protein expression levels were significantly reduced in 54 cases of human nasopharyngeal carcinoma compared with 16 cases of normal nasopharyngeal epithelia. Parkin-methylated cases showed significantly lower mRNA and protein expression levels compared with unmethylated cases. After 5-aza-2-deoxycytidine treatment, parkin mRNA expression was restored in CNE1 and CNE2; 92.59% (50/54) of nasopharyngeal carcinoma demonstrated genomic instability. Parkin is frequently inactivated by promoter methylation, and its mRNA and protein expression correlate with lymph node metastasis and genomic instability. Parkin deficiency probably promotes tumorigenesis in nasopharyngeal carcinoma.

Celecoxib induces proliferation and Amphiregulin production in colon subepithelial myofibroblasts, activating erk1-2 signaling in synergy with EGFR.

PubMed

Benelli, Roberto; Venè, Roberta; Minghelli, Simona; Carlone, Sebastiano; Gatteschi, Beatrice; Ferrari, Nicoletta

2013-01-01

The COX-2 inhibitor Celecoxib, tested in phase III trials for the prevention of sporadic colon adenomas, reduced the appearance of new adenomas, but was unable to affect the incidence of colon cancer. Moreover the 5years follow-up showed that patients discontinuing Celecoxib treatment had an increased incidence of adenomas as compared to the placebo arm. In the APC(min/+) mouse model short term treatment with Celecoxib reduced gut adenomas, but a prolonged administration of the drug induced fibroblast activation and intestinal fibrosis with a final tumor burden. The way Celecoxib could directly activate human colon myofibroblasts (MF) has not yet been investigated. We found that MF are activated by non toxic doses of Celecoxib. Celecoxib induces erk1-2 and Akt phosphorylation within 5'. This short term activation is apparently insufficient to cause phenotypic changes, but the contemporary triggering of EGFR causes an impressive synergic effect inducing MF proliferation and the neo-expression and release of Amphiregulin (AREG), a well known EGFR agonist involved in colon cancer progression. As a confirm to these observations, the erk inhibitor U0126 and the EGFR inhibitors Tyrphostin and Cetuximab were able to contrast AREG induction. Our data provide evidence that Celecoxib directly activates MF empowering EGFR signaling. According to these results the association with EGFR (or erk1-2) inhibitors could abolish the off-target activity of Celecoxib, possibly extending the potential of this drug for colon cancer prevention. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Nasopharyngeal angiofibroma: Our experience and literature review

PubMed Central

Martins, Mariane Barreto Brandão; de Lima, Francis Vinicius Fontes; Mendonça, Carlos Alberto; de Jesus, Eduardo Passos Fiel; Santos, Arlete Cristina Granizo; Barreto, Valéria Maria Prado; Santos, Ronaldo Carvalho

2013-01-01

Summary Introduction: Juvenile nasopharyngeal angiofibroma is a rare, highly vascular, and histologically benign tumor, generally observed in male adolescents. It shows very aggressive behavior due to local invasiveness and is associated with various symptoms. Juvenile nasopharyngeal angiofibroma originates in the sphenopalatine forame, causing epistaxes and nasal obstruction. Objective: To retrospectively describe our experience in the diagnosis and treatment of patients with juvenile nasopharyngeal angiofibroma. Scientific drawing: Retrospective, descriptive study conducted after approval from the Ethics Committee of the Federal University of Sergipe (protocol 0114.0.107.000 -11). Methods: We analyzed findings in 20 patients who underwent surgery between 2004 and 2011. Factors analyzed include patient age and gender, symptoms, stages, treatment, length of surgery, intraoperatory bleeding, postoperative need for nasal tampons, hospitalization time, complications, and tumor recurrence. Results: Patients were aged 10–29 years. All patients were treated surgically, including 17 who underwent endoscopic surgery. The mean operation time was 120 min, and the mean bleeding volume was 300 mL. Seventeen patients required clamping of the external carotids and tumor embolization. Conclusion: Endoscopic surgery alone or with other conventional techniques was safe for the treatment of angiofibromas of different stages. PMID:25991988

Sulfhydryl blocker-induced colitis in the rat: immunological changes in thymus gland and colonic mucosa.

PubMed

Suzuki, H; Hibi, T; Oda, M; Hosoda, Y; Mori, M; Miura, S; Tanaka, S; Watanabe, M; Tsuchiya, M

1994-01-01

The study was designed to examine the changes of thymus in sulfhydryl blocker-induced colitis. We used N-ethylmaleimide (NEM) as sulfhydryl blockers. Fasted male Sprague-Dawley rats were given 3% NEM in 1% methyl cellulose into the colon. N-ethylmaleimide treatment caused severe diarrhoea with bleeding for the first 7 days. At autopsy, adhesions, colon dilatation, and single or multiple erosions and ulcers were observed. Time-course studies revealed that the lesions were most extensive and severe 3 or 7 days after the administration of NEM. Histological examination of colon on the 3rd day after NEM treatment demonstrated mucosal erosion, oedema and extensive infiltration of neutrophils. The mucosal lesions extended into the submucosa and muscle on the 7th day after NEM treatment. Immunohistochemical studies showed that T cells and macrophages were markedly increased in the lamina propria of colonic mucosa. After 3 weeks, the infiltration of chronic inflammatory cells was observed and regeneration of the mucosa was noticed. The thymus gland was significantly decreased in weight and size on the 3rd day after NEM treatment, but the weight loss of thymus gland was regained in 3 weeks. Transient atrophy of thymus gland was noticed in this colitis model. The phenotypes of thymocytes were not influenced by NEM treatment. It is concluded that the thymus abnormalities in human ulcerative colitis are not induced in this animal model and that other chronic models are necessary for the elucidation of the immunological abnormalities, including thymus abnormalities.

Radiation-induced temporo-mandibular joint disorder in post-radiotherapy nasopharyngeal carcinoma patients: assessment and treatment.

PubMed

Wu, Vincent W C; Lam, Ying-Na

2016-06-01

Nasopharyngeal carcinoma (NPC) is endemic in southern China, and its incidence in Hong Kong is relatively high. Radiotherapy is the mainstay treatment for NPC due to its relatively high radiosensitivity and deep-seated anatomical position, which is not readily accessible by surgery. Although the technique of radiotherapy in NPC has been advancing and offers promising treatment outcome, complications around the irradiation areas are inevitable and the quality of life of the post-radiotherapy patients is often compromised. Trismus, which is defined as the restricted mouth opening or jaw movement due to the disorder of temporo-mandibular joint (TMJ), is one of the possible late complications for radiotherapy of NPC and is found in 5-17% of the post-radiotherapy (post-RT) patients. Trismus at early stage may only affect the speech, but in severe cases nutritional intake and oral hygiene condition may deteriorate seriously. This article reviewed the possible causes of radiation-induced TMJ damage, the various assessments including imaging modalities and possible treatments. The conclusion is that the availability of simple, yet effective examinations for trismus is essential for delaying the progression and restoring TMJ functions. Although there is no absolutely effective treatment for trismus, many supportive, restorative and palliative management are possible under different clinical situations.

Norovirus in feces and nasopharyngeal swab of children with and without acute gastroenteritis symptoms: First report of GI.5 in Brazil and GI.3 in nasopharyngeal swab.

PubMed

Dábilla, Nathânia; Nunes Vieira Almeida, Tâmera; Carvalho Rebouças Oliveira, Anniely; Kipnis, André; Neres Silva, Thairiny; Souza Fiaccadori, Fabíola; Teixeira de Sousa, Teresinha; de Paula Cardoso, Divina das Dôres; Souza, Menira

2017-02-01

Noroviruses (NoVs) are an important cause of acute gastroenteritis (AGE), worldwide. To evaluate the frequency, viral load and molecular profile of NoV in fecal and nasopharyngeal swab samples from hospitalized children, and to determine children's secretor status. From May 2014 to May 2015, 219 children were included in the study, 96 with gastroenteric symptoms and 123 without gastroenteric symptoms. All fecal and nasopharyngeal swab samples were screened by TaqMan RT-qPCR duplex (GI/GII NoV) and quality samples were characterized by genomic sequencing. Norovirus positivity rate in feces was 15.4% in asymptomatic and 18.8% in the symptomatic group. The median viral loads in feces were 2.69×10 8 GC/g and 4.32×10 7 GC/g from children with or without AGE symptoms, respectively. In nasopharyngeal swab samples, the NoV positivity was 11.4% in symptomatic children, with a median viral load of 2.20×10 7 GC/mL and 6.5% in asymptomatic children, with an average viral load of 1.73×10 6 GC/mL. In only two cases NoV was detected in both samples. A considerable genomic variability was observed in feces, with six genotypes being detected, as follows: GII.4, GII.6, GI.3 and GII.3, GI.2 and GI.5. Two GI.3 was detected in nasopharyngeal swab. Our data reveal considerable NoV frequencies in both nasopharyngeal and fecal samples from symptomatic and asymptomatic children. Higher viral loads were detected in samples from AGE symptomatic children, when compared to asymptomatic children. High genomic variability was observed, with this being the first report of GI.5 NoV in Brazil and of GI.3 in nasopharyngeal swab samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Beneficial influence of ellagic acid on biochemical indexes associated with experimentally induced colon carcinogenesis.

PubMed

Syed, Umesalma; Ganapasam, Sudhandiran

2017-01-01

To elucidate the key biochemical indexes associated with 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis and the modulatory efficacy of a dietary polyphenol, ellagic acid (EA). Wistar rats were chosen to study objective, and were divided into 4 groups; Group 1-control rats; Group 2-rats received EA (60 mg/kg body weight/day, orally); rats in Group 3-induced with DMH (20 mg/kg body weight) subcutaneously for 15 weeks; DMH-induced Group 4 rats were initiated with EA treatment. We examined key citric acid cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and the activities of respiratory chain enzymes NADH dehydrogenase and Cytochrome-C-oxidase and membrane-bound enzyme profiles (Na +/K + ATPase, Ca 2+ ATPase and Mg 2+ ATPase), activities of lysosomal proteases such as β-D-glucuronidase, β-galactosidase and N-acety-β-D-glucosaminidase and cellular thiols (oxidized glutathione, protein thiols, and total thiols). It was found that administration of DMH to rats decreased both mitochondrial and membrane-bound enzymes activities, increased activities of lysosomal enzymes and further modulates cellular thiols levels. Treatment with EA significantly restored the mitochondrial and ATPases levels and further reduced lysosomal enzymes to near normalcy thereby restoring harmful effects induced by DMH. EA treatment was able to effectively restore the detrimental effects induced by DMH, which proves the chemoprotective function of EA against DMH-induced experimental colon carcinogenesis.

β-Glucans in food modify colonic microflora by inducing antimicrobial protein, calprotectin, in a Dectin-1-induced-IL-17F-dependent manner.

PubMed

Kamiya, T; Tang, C; Kadoki, M; Oshima, K; Hattori, M; Saijo, S; Adachi, Y; Ohno, N; Iwakura, Y

2018-05-01

Dectin-1 (gene symbol: Clec7a) is a receptor for β-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a -/- mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell expansion is caused by expansion of commensal Lactobacillus murinus whose growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this report, we showed that S100A8 was mainly produced by mouse colonic epithelial cells. S100A8 was not induced directly by Dectin-1 but by Dectin-1-induced cytokines, especially interleukin-17F (IL-17F), that were produced by several types of innate immune cells including CD11c + /CD11b + myeloid cells in colonic lamina propria. S100A8/A9 heterodimer preferentially suppressed the growth of L. murinus that was increased in both Clec7a -/- and Il17f -/- mice. Furthermore, similar expansion of L. murinus and DSS-colitis resistance were observed in mice fed with β-glucan-free food. These observations suggest that food-derived β-glucans control the specific commensal microbiota via the Dectin-1-IL-17F-calprotectin axis to maintain the intestinal homeostasis.

Triptolide abrogates growth of colon cancer and induces cell cycle arrest by inhibiting transcriptional activation of E2F.

PubMed

Oliveira, Amanda; Beyer, Georg; Chugh, Rohit; Skube, Steven J; Majumder, Kaustav; Banerjee, Sulagna; Sangwan, Veena; Li, Lihua; Dawra, Rajinder; Subramanian, Subbaya; Saluja, Ashok; Dudeja, Vikas

2015-06-01

Despite significant progress in diagnostics and therapeutics, over 50 thousand patients die from colorectal cancer annually. Hence, there is urgent need for new lines of treatment. Triptolide, a natural compound isolated from the Chinese herb Tripterygium wilfordii, is effective against multiple cancers. We have synthesized a water soluble analog of triptolide, named Minnelide, which is currently in phase I trial against pancreatic cancer. The aims of the current study were to evaluate whether triptolide/Minnelide is effective against colorectal cancer and to elucidate the mechanism by which triptolide induces cell death in colorectal cancer. Efficacy of Minnelide was evaluated in subcutaneous xenograft and liver metastasis model of colorectal cancer. For mechanistic studies, colon cancer cell lines HCT116 and HT29 were treated with triptolide and the effect on viability, caspase activation, annexin positivity, lactate dehydrogenase release, and cell cycle progression was evaluated. Effect of triptolide on E2F transcriptional activity, mRNA levels of E2F-dependent genes, E2F1- retinoblastoma protein (Rb) binding, and proteins levels of regulator of G1-S transition was also measured. DNA binding of E2F1 was evaluated by chromatin immunoprecipitation assay. Triptolide decreased colon cancer cell viability in a dose- and time-dependent fashion. Minnelide markedly inhibited the growth of colon cancer in the xenograft and liver metastasis model of colon cancer and more than doubles the median survival of animals with liver metastases from colon cancer. Mechanistically, we demonstrate that at low concentrations triptolide induces apoptotic cell death but at higher concentrations it induces cell cycle arrest. Our data suggest that triptolide is able to induce G1 cell cycle arrest by inhibiting transcriptional activation of E2F1. Our data also show that triptolide downregulates E2F activity by potentially modulating events downstream of DNA binding. Therefore, we conclude

Glutamine Supplementation Attenuates Ethanol-Induced Disruption of Apical Junctional Complexes in Colonic Epithelium and Ameliorates Gut Barrier Dysfunction and Fatty Liver in Mice

PubMed Central

Chaudhry, Kamaljit K.; Shukla, Pradeep K.; Mir, Hina; Manda, Bhargavi; Gangwar, Ruchika; Yadav, Nikki; McMullen, Megan; Nagy, Laura E.; Rao, RadhaKrishna

2015-01-01

Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of glutamine in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed Gln-free diet and absent in mice fed Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury. PMID:26365579

Nasopharyngeal carriage of pneumococci in Gambian children and in their families.

PubMed

Lloyd-Evans, N; O'Dempsey, T J; Baldeh, I; Secka, O; Demba, E; Todd, J E; Mcardle, T F; Banya, W S; Greenwood, B M

1996-10-01

Nasopharyngeal carriage of pneumococci is prevalent among children in developing countries but little is known about the relationship of nasopharyngeal carriage to invasive disease or about the way in which pneumococci spread within households. To determine the prevalence of nasopharyngeal carriage in healthy and sick Gambian children and to investigate transmission within households. Nasopharyngeal swabs were obtained by the per nasal route and cultured for pneumococci on selective media. Pneumococci were serotyped with the use of latex particles coated with type-specific antisera. Pneumococci were isolated from the nasopharynx of 73 (90.1%) of 81 children with invasive pneumococcal disease, 86 (76.1%) of 113 healthy, age-matched control children and 911 (85.1%) of 1071 sick children. Pneumococci belonging to serotypes 1, 14 and 12 were isolated significantly more frequently from cases than from matched controls. In 43 (76.8%) of 56 children with invasive disease, pneumococci isolated from the nasopharynx and from the blood or other sterile site belonged to the same serotype. Pneumococci of the same serotype as the bacterium responsible for invasive disease in a child were obtained from 72 (8.5%) of 843 family members, most frequently from young siblings of the case patients. Nasopharyngeal carriage of pneumococci is more prevalent among young Gambian children than among adults and invasive infections are probably acquired more frequently from siblings than from parents. However, further studies are needed to confirm this hypothesis with more discriminating markers than polysaccharide serotyping.

Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway.

PubMed

Li, Qing-chun; Liang, Yun; Tian, Yuan; Hu, Guang-rui

2016-01-01

In the current study the antiproliferative effect of arctigenin, plant lignin, was evaluated on human colon cancer cell line HT-29. Furthermore, attempts were made to explore the signaling mechanism which may be responsible for its effect. Cell growth inhibition was assessed by MTT and LDH assays. Flow cytometric analysis was performed to determine cell arrest in the cell cycle phase and apoptosis. Furthermore, to confirm the apoptotic activity of arctigenin, caspase-9 and -3 activities analysis was performed. The levels of reactive oxygen species (ROS) and p38 mitogen activated protein kinase (MAPK) were investigated to determine their role in inducing apoptosis in arctigenin-treated HT-29 colon cancer cell line. MTT and LDH results demonstrated significant cell growth inhibitory effect of arctigenin on HT-29 cells in a dose-dependent manner. Furthermore, increase in cell number arrested at G2/M phase was observed in flow cytometric analysis upon arctigenin treatment. In addition, arctigenin increased the apoptotic ratio in a dose-dependent manner. The involvement of intrinsic apoptotic pathway was indicated by the activation of caspase-9 and -3. Moreover, increased ROS production, activation of p38 MAPK and changes in mitochondrial membrane potential (ΔΨm) also revealed the role of intrinsic apoptotic signaling pathway in cell growth inhibition after arctigenin exposure. Arctigenin induces apoptosis in HT-29 colon cancer cells by regulating ROS and p38 MAPK pathways.

Influence of simethicone and alverine on stress-induced alterations of colonic permeability and sensitivity in rats: beneficial effect of their association.

PubMed

Bueno, Lionel; Beaufrand, Catherine; Theodorou, Vassilia; Andro-Delestrain, Marie-Christine

2013-04-01

Alverine, an antispasmodic agent for the treatment of irritable bowel syndrome (IBS), may be combined with simethicone, a protective agent of the mucosa. Stress is a major factor triggering abdominal pain in IBS and causing hypersensitivity to colonic distension in animals through an increased colonic permeability. The antinociceptive effects of alverine and simethicone, separately or in association, were evaluated on stress-induced colonic hypersensitivity to distension in rats. The influence of simethicone on altered permeability was also tested. Groups of 8-10 female adult Wistar rats (200-250 g) housed individually were used. Gut paracellular permeability was evaluated after 2 h of partial restraint stress using oral gavage with ⁵¹Cr-EDTA and 24 h of urine collection. The number of abdominal cramps during colonic distension was evaluated in animals equipped with electrodes on their abdominal striated muscles. At 200 mg/kg p.o. twice a day, but not at lower doses, simethicone reduced stress-induced increase of colonic permeability and hypersensitivity to distension. Administered alone at 10 mg/kg p.o., alverine also reduced stress-induced hypersensitivity to distension; lower doses were inactive. However, alverine administered at an inactive dose with simethicone suppressed stress-induced hypersensitivity to distension. We conclude that both simethicone and alverine have visceral antinociceptive effects by two different mechanisms and that simethicone exerts a potentiating effect on the antinociceptive action of alverine. © 2013 The Authors. JPP © 2013. Royal Pharmaceutical Society.

Protective Immunity and Reduced Renal Colonization Induced by Vaccines Containing Recombinant Leptospira interrogans Outer Membrane Proteins and Flagellin Adjuvant

PubMed Central

Monaris, D.; Sbrogio-Almeida, M. E.; Dib, C. C.; Canhamero, T. A.; Souza, G. O.; Vasconcellos, S. A.; Ferreira, L. C. S.

2015-01-01

Leptospirosis is a global zoonotic disease caused by different Leptospira species, such as Leptospira interrogans, that colonize the renal tubules of wild and domestic animals. Thus far, attempts to develop effective leptospirosis vaccines, both for humans and animals, have failed to induce immune responses capable of conferring protection and simultaneously preventing renal colonization. In this study, we evaluated the protective immunity induced by subunit vaccines containing seven different recombinant Leptospira interrogans outer membrane proteins, including the carboxy-terminal portion of the immunoglobulinlike protein A (LigAC) and six novel antigens, combined with aluminum hydroxide (alum) or Salmonella flagellin (FliC) as adjuvants. Hamsters vaccinated with the different formulations elicited high antigen-specific antibody titers. Immunization with LigAC, either with alum or flagellin, conferred protective immunity but did not prevent renal colonization. Similarly, animals immunized with LigAC or LigAC coadministered with six leptospiral proteins with alum adjuvant conferred protection but did not reduce renal colonization. In contrast, immunizing animals with the pool of seven antigens in combination with flagellin conferred protection and significantly reduced renal colonization by the pathogen. The present study emphasizes the relevance of antigen composition and added adjuvant in the efficacy of antileptospirosis subunit vaccines and shows the complex relationship between immune responses and renal colonization by the pathogen. PMID:26108285

Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

ClinicalTrials.gov

2018-01-04

Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7

Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma

ClinicalTrials.gov

2018-04-20

Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Nasopharyngeal Undifferentiated Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7

PROMOTION OF TRIHALOMETHANE-INDUCED COLON, ABERRANT CRYPT FOCI (ACF) BY A HIGH FAT DIET

EPA Science Inventory

Abstract:

Bromodichloromethane (BOCM) and tribromomethane (TBM) enhanced neoplasia in the large intestine of rats when given by corn oil gavage; BOCM in the drinking water to male rats did not induce colon tumors, but did increase liver tumors. However, TBM and a mixture o...

Matrix Stiffness Corresponding to Strictured Bowel Induces a Fibrogenic Response in Human Colonic Fibroblasts

PubMed Central

Johnson, Laura A.; Rodansky, Eva S.; Sauder, Kay L.; Horowitz, Jeffrey C.; Mih, Justin D.; Tschumperlin, Daniel J.; Higgins, Peter D.

2013-01-01

Background Crohn’s disease is characterized by repeated cycles of inflammation and mucosal healing which ultimately progress to intestinal fibrosis. This inexorable progression towards fibrosis suggests that fibrosis becomes inflammation-independent and auto-propagative. We hypothesized that matrix stiffness regulates this auto-propagation of intestinal fibrosis. Methods The stiffness of fresh ex vivo samples from normal human small intestine, Crohn’s disease strictures, and the unaffected margin were measured with a microelastometer. Normal human colonic fibroblasts were cultured on physiologically normal or pathologically stiff matrices corresponding to the physiological stiffness of normal or fibrotic bowel. Cellular response was assayed for changes in cell morphology, α-smooth muscle actin (αSMA) staining, and gene expression. Results Microelastometer measurements revealed a significant increase in colonic tissue stiffness between normal human colon and Crohn’s strictures as well as between the stricture and adjacent tissue margin. In Ccd-18co cells grown on stiff matrices corresponding to Crohn’s strictures, cellular proliferation increased. Pathologic stiffness induced a marked change in cell morphology and increased αSMA protein expression. Growth on a stiff matrix induced fibrogenic gene expression, decreased matrix metalloproteinase and pro-inflammatory gene expression, and was associated with nuclear localization of the transcriptional cofactor MRTF-A. Conclusions Matrix stiffness, representative of the pathological stiffness of Crohn’s strictures, activates human colonic fibroblasts to a fibrogenic phenotype. Matrix stiffness affects multiple pathways suggesting the mechanical properties of the cellular environment are critical to fibroblast function and may contribute to autopropagation of intestinal fibrosis in the absence of inflammation, thereby contributing to the intractable intestinal fibrosis characteristic of Crohn’s disease. PMID

miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4

PubMed Central

Zhang, Chen-Peng; Xiao, Qian; Lin, Xiao-Lin

2017-01-01

Aim Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this study were to identify key miRNAs in colon cancer lymphangiogenesis and to investigate its target and mechanism. Methods miRNA microarray analysis was conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that were regulated by co-cultured human colon cancer cells. Gain- and loss-of-function studies were performed to determine the function of miR-27a, a top hint, on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics prediction and experimental validation were performed to identify miR-27a target genes in lymphangiogenesis. Results We found that expression of miR-27a in HLECs was induced by co-culturing with colon cancer cells. Over-expression of miR-27a in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of miR-27a reduced lymphatic tube formation and migration. Luciferase reporter assays showed that miR-27a directly targeted SMAD4, a pivotal component of the TGF-β pathway. In addition, gain-of-function and loss-of-function experiments showed that SMAD4 negatively regulated the length of lymphatic vessels formed by HLECs and migration. Conclusions Our data indicated that colon cancer cell induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by targeting SMAD4. Our finding implicated miR-27a as a potential target for new anticancer therapies in colon cancer. PMID:29065177

Density and Duration of Pneumococcal Carriage Is Maintained by Transforming Growth Factor β1 and T Regulatory Cells

PubMed Central

Coward, William R.; Gritzfeld, Jenna F.; Richards, Luke; Garcia-Garcia, Francesc J.; Dotor, Javier; Gordon, Stephen B.

2014-01-01

Rationale: Nasopharyngeal carriage of Streptococcus pneumoniae is a prerequisite for invasive disease, but the majority of carriage episodes are asymptomatic and self-resolving. Interactions determining the development of carriage versus invasive disease are poorly understood but will influence the effectiveness of vaccines or therapeutics that disrupt nasal colonization. Objectives: We sought to elucidate immunological mechanisms underlying noninvasive pneumococcal nasopharyngeal carriage. Methods: Pneumococcal interactions with human nasopharyngeal and bronchial fibroblasts and epithelial cells were investigated in vitro. A murine model of nasopharyngeal carriage and an experimental human pneumococcal challenge model were used to characterize immune responses in the airways during carriage. Measurements and Main Results: We describe the previously unknown immunological basis of noninvasive carriage and highlight mechanisms whose perturbation may lead to invasive disease. We identify the induction of active transforming growth factor (TGF)-β1 by S. pneumoniae in human host cells and highlight the key role for TGF-β1 and T regulatory cells in the establishment and maintenance of nasopharyngeal carriage in mice and humans. We identify the ability of pneumococci to drive TGF-β1 production from nasopharyngeal cells in vivo and show that an immune tolerance profile, characterized by elevated TGF-β1 and high nasopharyngeal T regulatory cell numbers, is crucial for prolonged carriage of pneumococci. Blockade of TGF-β1 signaling prevents prolonged carriage and leads to clearance of pneumococci from the nasopharynx. Conclusions: These data explain the mechanisms by which S. pneumoniae colonize the human nasopharynx without inducing damaging host inflammation and provide insight into the role of bacterial and host constituents that allow and maintain carriage. PMID:24749506

Screening and identification of proteins mediating senna induced gastrointestinal motility enhancement in mouse colon

PubMed Central

Wang, Xin; Zhong, Yue-Xia; Lan, Mei; Zhang, Zong-You; Shi, Yong-Quan; Lu, Ju; Ding, Jie; Wu, Kai-Cun; Jin, Jian-Ping; Pan, Bo-Rong; Fan, Dai Min

2002-01-01

AIM: To isolate the proteins involved in pharmacologic action of senna extract (SE) from mouse gastrointestinal tract and to explore the molecular mechanism of gastrointestinal motility change induced by SE. METHODS: SE was administrated to mice by different routes. Gastrointestinal motility of mice was observed using cathartic, gastrointestinal propellant movement experiments and X-ray analysis. Mouse model for gastrointestinal motility enhancement was established through continuous gastric administration of SE at progressively increased dose. At 3 h and week 3, 4, 6 and 10, morphological changes of gastrointestinal tissues were found under light microscope. Ultrastructural changes of intestinal and colonic tissues at week 6 were observed under transmission electron microscope. The colonic proteomic changes in model mice were examined by two-dimension polyacrylamide gel electrophoresis with immobilized pH gradient isoelectric focusing to screen the differentially expressed proteins, and their molecular masses and isoelectric points were determined. Two N-terminal sequences of the samples were also determined by mass spectrometry. RESULTS: SE (0.3 g) caused diarrhea after gastric administration in 1-6 h and enhanced gastrointestinal propellant (65.1% ± 7.5%; 45.8% ± 14.6%,P < 0.01) in mice, but intramuscular and hypodermic injection had no cathartic effect. X-ray analysis of gastrointestinal motility demonstrated that gastric administration of SE enhanced gastric evacuation and gastrointestinal transferring function. At 3 h and week 3 and 4 after gastric administration of SE, light microscopic examination revealed no apparent change in gastrointestinal mucosal tissues, but transmission electron microscopic examination revealed inflammatory changes in whole layer of intestinal and colonic wall. Twenty differential proteins were detected in the colonic tissues of the model mice by two-dimensional electrophoresis, and the N-terminal amino acid sequences of two

Nasopharyngeal carcinoma presented as cavernous sinus tumour.

PubMed

Moona, Mohammad Shafi; Mehdi, Itrat

2011-12-01

A 32 year Libyan male presented with the complaints of headache and diplopia. He was diagnosed with a cavernous sinus meningioma on the basis of MRI findings but no initial biopsy was taken. Depending on the radiologic diagnosis the patient was treated with gamma knife surgery twice, abroad. During follow up he developed left ear deafness and left cervical lymph adenopathy. An ENT evaluation with biopsy from the nasopharynx and cervical lymph node was taken. The histopathologic diagnosis of the resected tumour showed a nasopharyngeal carcinoma with cervical lymph node metastasis (poorly differentiated lympho-epithelial carcinoma). The cavernous sinus tumour which was initially treated as a meningioma was in fact metastasis from the nasopharyngeal carcinoma, making this an interesting and rare occurrence.

Isothiocyanates from Broccolini seeds induce apoptosis in human colon cancer cells: proteomic and bioinformatic analyses.

PubMed

Yang, Yanjing; Yan, Huidan; Li, Yuqin; Yang, Shang-Tian; Zhang, Xuewu

2011-05-01

Isothiocyanates (ITCs) have been shown to possess antitumor activity in colon cancer, however, the detailed mechanism is still unclear. The objective of this study was to investigate apoptosis-inducing activity of ITCs from Broccolini seeds and proteomic changes in SW480 cells, and to identify the molecular pathways responsible for the anticancer action of ITCs. We found that ITCs induces SW480 cells apoptosis in a dose-dependent manner by using MTT assay, phase contrast microscope and flow cytometry, and the IC50 was calculated to be 77.72 microg/ml, superior to the chemotherapeutical drug 5-flurouracil. Subsequently, 15 altered proteins in ITCs treated SW480 cells were identified. Further bioinformatics analysis predicted the potential pathways for ITCs to induce apoptosis of SW480 cells. In conclusion, this is the first report to investigate anticancer activity of ITCs from Broccolini seeds and its mechanism of action by proteomics analysis. Our observations provide potential therapeutic targets for colon cancer inhibitor intervention and implicate the development of novel anti-cancer therapeutic strategies.

δ- and γ-Tocopherols Inhibit PhIP/DSS-induced Colon Carcinogenesis by Protection against Early Cellular and DNA Damages

PubMed Central

Chen, Jayson X.; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S.

2017-01-01

Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T) and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 weeks. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. PMID:27175800

Corticotropin-releasing factor stimulates colonic motility via muscarinic receptors in the rat

PubMed Central

Kim, Kyung-Jo; Kim, Ki Bae; Yoon, Soon Man; Han, Joung-Ho; Chae, Hee Bok; Park, Seon Mee; Youn, Sei Jin

2017-01-01

AIM To measure exogenous corticotropin-releasing factor (CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility. METHODS The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous CRF was administered in a stepwise manner and the concentration of CRF yielding maximal colonic motility was selected. After recording basal colonic motility, hexamethonium, phentolamine, propranolol, atropine and tetrodotoxin were infused into the isolated colon. Initially, only the test drug was infused; then, CRF was added. The motility index was expressed as percentage change over basal level. RESULTS Administration of 1.4, 14.4, 144 and 288 pmol/L CRF progressively increased colonic motility in the proximal and distal colon. Infusion of atropine or tetrodotoxin reduced CRF-induced motility of both the proximal and distal colon, whereas hexamethonium, phentolamine and propranolol had no effect. CONCLUSION CRF-induced colonic motility appears to be mediated by local cholinergic signaling via muscarinic receptors. Muscarinic receptors are potential targets for counteracting CRF-induced colonic hypermotility. PMID:28638222

Stridor: an unusual presentation of juvenile nasopharyngeal angiofibroma

PubMed Central

Singh, Hitendra Prakash; Kumar, Sunil; Vashishtha, Madhukar; Agarwal, Satya Prakash

2014-01-01

Nasopharyngeal angiofibroma is a rare and benign disease, which is mainly found in adolescent male subjects. It is usually diagnosed on clinical grounds on the basis of its presenting symptoms of nasal obstruction, nasal mass and most importantly unprovoked recurrent moderate to severe epistaxis. Imaging studies are only needed to confirm the diagnosis and formulate the management plan. A case of juvenile nasopharyngeal angiofibroma is presented here, which presented to us with severe respiratory distress and stridor. Urgent tracheostomy had to be performed before definitive management could be started. Definitive treatment was excision through modified transpalatal with sublabial route, which resulted in successful outcome. PMID:24711471

Stridor: an unusual presentation of juvenile nasopharyngeal angiofibroma.

PubMed

Singh, Hitendra Prakash; Kumar, Sunil; Vashishtha, Madhukar; Agarwal, Satya Prakash

2014-04-07

Nasopharyngeal angiofibroma is a rare and benign disease, which is mainly found in adolescent male subjects. It is usually diagnosed on clinical grounds on the basis of its presenting symptoms of nasal obstruction, nasal mass and most importantly unprovoked recurrent moderate to severe epistaxis. Imaging studies are only needed to confirm the diagnosis and formulate the management plan. A case of juvenile nasopharyngeal angiofibroma is presented here, which presented to us with severe respiratory distress and stridor. Urgent tracheostomy had to be performed before definitive management could be started. Definitive treatment was excision through modified transpalatal with sublabial route, which resulted in successful outcome.

Real time near-infrared Raman spectroscopy for the diagnosis of nasopharyngeal cancer.

PubMed

Ming, Lim Chwee; Gangodu, Nagaraja Rao; Loh, Thomas; Zheng, Wei; Wang, Jianfeng; Lin, Kan; Zhiwei, Huang

2017-07-25

Near-infrared (NIR) Raman spectroscopy has been investigated as a tool to differentiate nasopharyngeal cancer (NPC) from normal nasopharyngeal tissue in an ex-vivo setting. Recently, we have miniaturized the fiber-optic Raman probe to investigate its utility in real time in-vivo surveillance of NPC patients. A posterior probability model using partial linear square (PLS) mathematical technique was constructed to verify the sensitivity and specificity of Raman spectroscopy in diagnosing NPC from post-irradiated and normal tissue using a diagnostic algorithm from three significant latent variables. NIR-Raman signals of 135 sites were measured from 79 patients with either newly diagnosed NPC (N = 12), post irradiated nasopharynx (N = 37) and normal nasopharynx (N = 30). The mean Raman spectra peaks identified differences at several Raman peaks at 853 cm-1, 940 cm-1, 1078 cm-1, 1335 cm-1, 1554 cm-1, 2885 cm-1 and 2940 cm-1 in the three different nasopharyngeal conditions. The sensitivity and specificity of distinguishing Raman signatures among normal nasopharynx versus NPC and post-irradiated nasopharynx versus NPC were 91% and 95%; and 77% and 96% respectively. Real time near-infrared Raman spectroscopy has a high specificity in distinguishing malignant from normal nasopharyngeal tissue in vivo, and may be investigated as a novel non-invasive surveillance tool in patients with nasopharyngeal cancer.

A Glucosamine-Specific Lectin from Green Dragon No. 8 Beans (Phaseolus vulgaris) Induced Apoptosis on Nasopharyngeal Carcinoma Cells

PubMed Central

Chan, Yau Sang; Xia, Lixin; Ng, Tzi Bun

2015-01-01

A lectin exhibiting antiproliferative activity on tumor cell lines but devoid of antifungal activity has been purified from Phaseolus vulgaris cv. Green Dragon no. 8 seeds. The lectin was a 60 kDa dimeric protein with two 30 kDa subunits. It was a glucosamine-specific lectin as implied from the inhibitory effect of glucosamine on hemagglutinating activity of the lectin. The steps for isolation of the lectin involved Affi-gel blue gel (affinity gel), Mono Q (anion exchanger), and Superdex 75 column (size exclusion). The lectin was purified 20.8-fold from the crude extract of the beans. The purified lectin showed antiproliferative activity on breast cancer MCF7 cell line and nasopharyngeal cancer HONE1 and CNE2 cell lines, but a low activity on normal skin fibroblast HSF98 cell line. The lectin was shown to induce apoptosis on HONE1 cells, as indicated by increased phosphatidylserine externalization and mitochondrial depolarization. It also blocked HONE1 cell division and kept the cells at the G2/M phase of the cell cycle. PMID:26290674

Epstein-Barr virus infection and nasopharyngeal carcinoma.

PubMed

Tsao, Sai Wah; Tsang, Chi Man; Lo, Kwok Wai

2017-10-19

Epstein-Barr virus (EBV) is associated with multiple types of human cancer, including lymphoid and epithelial cancers. The closest association with EBV infection is seen in undifferentiated nasopharyngeal carcinoma (NPC), which is endemic in the southern Chinese population. A strong association between NPC risk and the HLA locus at chromosome 6p has been identified, indicating a link between the presentation of EBV antigens to host immune cells and NPC risk. EBV infection in NPC is clonal in origin, strongly suggesting that NPC develops from the clonal expansion of a single EBV-infected cell. In epithelial cells, the default program of EBV infection is lytic replication. However, latent infection is the predominant mode of EBV infection in NPC. The establishment of latent EBV infection in pre-invasive nasopharyngeal epithelium is believed to be an early stage of NPC pathogenesis. Recent genomic study of NPC has identified multiple somatic mutations in the upstream negative regulators of NF-κB signalling. Dysregulated NF-κB signalling may contribute to the establishment of latent EBV infection in NPC. Stable EBV infection and the expression of latent EBV genes are postulated to drive the transformation of pre-invasive nasopharyngeal epithelial cells to cancer cells through multiple pathways.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

Curcumin ameliorates the tumor-enhancing effects of a high-protein diet in an azoxymethane-induced mouse model of colon carcinogenesis.

PubMed

Byun, So-Young; Kim, Dan-Bi; Kim, Eunjung

2015-08-01

An increasing number of reports suggest that a high-protein diet (HPD) is associated with an increased risk for colorectal cancer (CRC). One of the proposed mechanisms is that an HPD increases the delivery of protein to the colon and generates various toxic metabolites that contribute to colon carcinogenesis. Curcumin was shown to exert significant preventive properties against CRC. We therefore hypothesized that curcumin can reverse the tumor-enhancing effects of an HPD. This study examined the effects of curcumin on the development of azoxymethane (AOM)-induced colorectal tumors in HPD-fed mice. A total of 30 female Balb/c mice were randomly divided into 3 groups: those fed a normal diet (20% casein), those fed an HPD (HPD; 50% casein), and those fed an HPD supplemented with curcumin (HPDC; 0.02% curcumin). The mice were subjected to an AOM-dextran sodium sulfate colon carcinogenesis protocol. Mice in the HPDC group exhibited a significant (40%) reduction in colorectal tumor multiplicity when compared with those in the HPD group. The expression of colonic inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), the levels of plasma inflammatory markers (nitric oxide and tumor necrosis factor-α), fecal ammonia, short- and branched-chain fatty acid levels, and the rate of colonocyte proliferation were significantly lower in the HPDC than the HPD group. In conclusion, curcumin inhibited the development of colorectal tumors in an AOM-induced mouse model of colon carcinogenesis by attenuating colonic inflammation, proliferation, and toxic metabolite production. Curcumin might be useful in the chemoprevention of CRC in individuals consuming an HPD. Copyright © 2015 Elsevier Inc. All rights reserved.

Lesioning of TRPV1 Expressing Primary Afferent Neurons Prevents PAR-2 Induced Motility, but Not Mechanical Hypersensitivity in the Rat Colon

PubMed Central

Suckow, Shelby K.; Anderson, Ethan M.; Caudle, Robert M.

2011-01-01

Background Proteinase activated receptor 2 (PAR-2) is expressed by many neurons in the colon, including primary afferent neurons that co-express transient receptor potential vanilloid 1 (TRPV1). Activation of PAR-2 receptors was previously found to enhance colonic motility, increase secretion and produce hypersensitivity to mechanical stimuli. This study examined the functional role of TRPV1/PAR-2 expressing neurons that innervate the colon by lesioning TRPV1 bearing neurons with the highly selective and potent TRPV1 agonist resiniferatoxin. Methods Colonic motility in response to PAR-2 activation was evaluated in vitro using isolated segments of descending colon and in vivo using manometry. Colonic mechanical nociceptive thresholds were measured using colorectal distension. TRPV1 expressing neurons were selectively lesioned with resiniferatoxin. Key Results In vitro the PAR-2 agonists trypsin and SLIGRL did not alter contractions of colon segments when applied alone, however, the agents enhanced acetylcholine stimulated contraction. In vivo, PAR-2 agonists administered intraluminally induced contractions of the colon and produced hypersensitivity to colorectal distention. The PAR-2 agonist enhancement of colonic contraction was eliminated when TRPV1 expressing neurons were lesioned with resiniferatoxin, but the PAR-2 agonist induced hypersensitivity remained in the lesioned animals. Conclusions and Inferences Our findings indicate that TRPV1/PAR-2 expressing primary afferent neurons mediate an extrinsic motor reflex pathway in the colon. These data, coupled with our previous studies, also indicate that the recently described colospinal afferent neurons are nociceptive, suggesting that these neurons may be useful targets for the pharmacological control of pain in diseases such as irritable bowel syndrome. PMID:22168801

Lesioning of TRPV1 expressing primary afferent neurons prevents PAR-2 induced motility, but not mechanical hypersensitivity in the rat colon.

PubMed

Suckow, S K; Anderson, E M; Caudle, R M

2012-03-01

Proteinase activated receptor 2 (PAR-2) is expressed by many neurons in the colon, including primary afferent neurons that co-express transient receptor potential vanilloid 1 (TRPV1). Activation of PAR-2 receptors was previously found to enhance colonic motility, increase secretion and produce hypersensitivity to mechanical stimuli. This study examined the functional role of TRPV1/PAR-2 expressing neurons that innervate the colon by lesioning TRPV1 bearing neurons with the highly selective and potent TRPV1 agonist resiniferatoxin. Colonic motility in response to PAR-2 activation was evaluated in vitro using isolated segments of descending colon and in vivo using manometry. Colonic mechanical nociceptive thresholds were measured using colorectal distension. Transient receptor potential vanilloid 1 expressing neurons were selectively lesioned with resiniferatoxin. In vitro, the PAR-2 agonists, trypsin and SLIGRL did not alter contractions of colon segments when applied alone, however, the agents enhanced acetylcholine stimulated contraction. In vivo, PAR-2 agonists administered intraluminally induced contractions of the colon and produced hypersensitivity to colorectal distention. The PAR-2 agonist enhancement of colonic contraction was eliminated when TRPV1 expressing neurons were lesioned with resiniferatoxin, but the PAR-2 agonist induced hypersensitivity remained in the lesioned animals. Our findings indicate that TRPV1/PAR-2 expressing primary afferent neurons mediate an extrinsic motor reflex pathway in the colon. These data, coupled with our previous studies, also indicate that the recently described colospinal afferent neurons are nociceptive, suggesting that these neurons may be useful targets for the pharmacological control of pain in diseases such as irritable bowel syndrome. © 2011 Blackwell Publishing Ltd.

Nasopharyngeal stenosis with concurrent hiatal hernia and megaesophagus in an 8-year-old cat.

PubMed

DeSandre-Robinson, Dana M; Madden, Stacey N; Walker, Jackson T

2011-06-01

A case of nasopharyngeal stenosis with secondary hiatal hernia is described. An 8-year-old castrated male domestic shorthair cat was referred for a chronic upper respiratory problem and presumptive vomiting. Despite conservative management by the primary care veterinarian, the cat's condition progressed. The cat was presented to an emergency facility prior to referral to a specialty hospital. On presentation, inspiratory stridor was evident. Thoracic radiography revealed a hiatal hernia. Computed tomography indicated pharyngeal edema and probable nasopharyngeal stenosis. Endoscopy confirmed the presence of nasopharyngeal stenosis consistent with either stricture or choanal atresia. Balloon dilation of the choana was performed. The hiatal hernia regressed spontaneously post-resolution of the nasopharyngeal stenosis. The cat remained asymptomatic at recheck 3 months later. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Endoscopic nasopharyngeal exploration at the end of conventional curettage adenoidectomy.

PubMed

Abdel-Aziz, Mosaad

2012-03-01

Adenoid hypertrophy (AH) is a common cause of airway obstruction in children and its recurrence after conventional curettage adenoidectomy is not rare. The purpose of this study is to assess the efficacy of endoscopic nasopharyngeal exploration at the end of curettage adenoidectomy on decreasing the incidence of adenoid re-hypertrophy. Three hundred and fifty children diagnosed as having AH, underwent conventional curettage adenoidectomy by a single surgeon. The cases were randomly divided into two equal groups A and B, group B were further subjected to nasopharyngeal exploration by the nasal endoscope after removal of their adenoids with cauterization of any visible residuals, while group A were not subjected to this endoscopic maneuver. Follow-up was carried out for at least 2 years; flexible nasopharyngoscopy was used for detection of recurrent AH. Cases that were not subjected to endoscopic nasopharyngeal exploration (group A) showed a high recurrence rate (6.6%), while explored cases (group B) showed a low incidence of recurrence (1.18%). Most recurrence of group A (6%) was detected within the first year of the follow-up period which may indicate re-growth of residual adenoidal tissues that were missed during conventional curettage adenoidectomy. Endoscopic nasopharyngeal exploration at the end of conventional curettage adenoidectomy is a useful method in decreasing the incidence of recurrent AH.

Alterations in the porcine colon microbiota induced by the gastrointestinal nematode Trichuris suis.

PubMed

Li, Robert W; Wu, Sitao; Li, Weizhong; Navarro, Karl; Couch, Robin D; Hill, Dolores; Urban, Joseph F

2012-06-01

Helminth parasites ensure their survival by regulating host immunity through mechanisms that dampen inflammation. These properties have recently been exploited therapeutically to treat human diseases. The biocomplexity of the intestinal lumen suggests that interactions between the parasite and the intestinal microbiota would also influence inflammation. In this study, we characterized the microbiota in the porcine proximal colon in response to Trichuris suis (whipworm) infection using 16S rRNA gene-based and whole-genome shotgun (WGS) sequencing. A 21-day T. suis infection in four pigs induced a significant change in the composition of the proximal colon microbiota compared to that of three parasite-naive pigs. Among the 15 phyla identified, the abundances of Proteobacteria and Deferribacteres were changed in infected pigs. The abundances of approximately 13% of genera were significantly altered by infection. Changes in relative abundances of Succinivibrio and Mucispirillum, for example, may relate to alterations in carbohydrate metabolism and niche disruptions in mucosal interfaces induced by parasitic infection, respectively. Of note, infection by T. suis led to a significant shift in the metabolic potential of the proximal colon microbiota, where 26% of all metabolic pathways identified were affected. Besides carbohydrate metabolism, lysine biosynthesis was repressed as well. A metabolomic analysis of volatile organic compounds (VOCs) in the luminal contents showed a relative absence in infected pigs of cofactors for carbohydrate and lysine biosynthesis, as well as an accumulation of oleic acid, suggesting altered fatty acid absorption contributing to local inflammation. Our findings should facilitate development of strategies for parasitic control in pigs and humans.

Alterations in the Porcine Colon Microbiota Induced by the Gastrointestinal Nematode Trichuris suis

PubMed Central

Wu, Sitao; Li, Weizhong; Navarro, Karl; Couch, Robin D.; Hill, Dolores; Urban, Joseph F.

2012-01-01

Helminth parasites ensure their survival by regulating host immunity through mechanisms that dampen inflammation. These properties have recently been exploited therapeutically to treat human diseases. The biocomplexity of the intestinal lumen suggests that interactions between the parasite and the intestinal microbiota would also influence inflammation. In this study, we characterized the microbiota in the porcine proximal colon in response to Trichuris suis (whipworm) infection using 16S rRNA gene-based and whole-genome shotgun (WGS) sequencing. A 21-day T. suis infection in four pigs induced a significant change in the composition of the proximal colon microbiota compared to that of three parasite-naive pigs. Among the 15 phyla identified, the abundances of Proteobacteria and Deferribacteres were changed in infected pigs. The abundances of approximately 13% of genera were significantly altered by infection. Changes in relative abundances of Succinivibrio and Mucispirillum, for example, may relate to alterations in carbohydrate metabolism and niche disruptions in mucosal interfaces induced by parasitic infection, respectively. Of note, infection by T. suis led to a significant shift in the metabolic potential of the proximal colon microbiota, where 26% of all metabolic pathways identified were affected. Besides carbohydrate metabolism, lysine biosynthesis was repressed as well. A metabolomic analysis of volatile organic compounds (VOCs) in the luminal contents showed a relative absence in infected pigs of cofactors for carbohydrate and lysine biosynthesis, as well as an accumulation of oleic acid, suggesting altered fatty acid absorption contributing to local inflammation. Our findings should facilitate development of strategies for parasitic control in pigs and humans. PMID:22493085

Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin.

PubMed

Hiramoto, Keiichi; Yokoyama, Satoshi; Yamate, Yurika

2017-03-01

We previously reported that ultraviolet (UV) A eye irradiation reduces the ulcerative colitis induced by dextran sodium sulfate (DSS). This study examined the effects of UVA on colon carcinoma induced by azoxymethane (AOM) and DSS. We irradiated the eyes of ICR mice with UVA at a dose of 110 kJ/m 2 using an FL20SBLB-A lamp for the experimental period. In mice treated with these drugs, the symptom of colon carcinoma was reduced by UVA eye irradiation. The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the blood were increased in AOM + DSS-treated mice; however, those levels were reduced by UVA eye irradiation. The expression of β-endorphin, methionine-enkephalin (OGF), μ-opioid receptor, and opioid growth factor receptor (OGFR) of the colon was increased in the AOM + DSS-treated mice, and these levels were increased further following UVA eye irradiation. When β-endorphin inhibitor was administered, the ameliorative effect of UVA eye irradiation was reduced, and the effect of eye irradiation disappeared entirely following the administration of naltrexone (inhibitor of both opioid receptor and OGFR). These results suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Intestinal Microbiota Plays a Role in Salmonella-Induced Colitis Independent of Pathogen Colonization

PubMed Central

Ferreira, Rosana B. R.; Gill, Navkiran; Willing, Benjamin P.; Antunes, L. Caetano M.; Russell, Shannon L.; Croxen, Matthew A.; Finlay, B. Brett

2011-01-01

The intestinal microbiota is composed of hundreds of species of bacteria, fungi and protozoa and is critical for numerous biological processes, such as nutrient acquisition, vitamin production, and colonization resistance against bacterial pathogens. We studied the role of the intestinal microbiota on host resistance to Salmonella enterica serovar Typhimurium-induced colitis. Using multiple antibiotic treatments in 129S1/SvImJ mice, we showed that disruption of the intestinal microbiota alters host susceptibility to infection. Although all antibiotic treatments caused similar increases in pathogen colonization, the development of enterocolitis was seen only when streptomycin or vancomycin was used; no significant pathology was observed with the use of metronidazole. Interestingly, metronidazole-treated and infected C57BL/6 mice developed severe pathology. We hypothesized that the intestinal microbiota confers resistance to infectious colitis without affecting the ability of S. Typhimurium to colonize the intestine. Indeed, different antibiotic treatments caused distinct shifts in the intestinal microbiota prior to infection. Through fluorescence in situ hybridization, terminal restriction fragment length polymorphism, and real-time PCR, we showed that there is a strong correlation between the intestinal microbiota composition before infection and susceptibility to Salmonella-induced colitis. Members of the Bacteroidetes phylum were present at significantly higher levels in mice resistant to colitis. Further analysis revealed that Porphyromonadaceae levels were also increased in these mice. Conversely, there was a positive correlation between the abundance of Lactobacillus sp. and predisposition to colitis. Our data suggests that different members of the microbiota might be associated with S. Typhimurium colonization and colitis. Dissecting the mechanisms involved in resistance to infection and inflammation will be critical for the development of therapeutic and

Multiparametric Detection of Antibodies against Different EBV Antigens to Predict Risk for Nasopharyngeal Carcinoma in a High-Risk Population of China.

PubMed

Chen, Hao; Chen, Shulin; Lu, Jie; Wang, Xueping; Li, Jianpei; Li, Linfang; Fu, Jihuan; Scheper, Thomas; Meyer, Wolfgang; Peng, Yu-Hui; Liu, Wanli

2017-09-01

In this study, we aimed to use the combined detection of multiple antibodies against Epstein-Barr virus (EBV) antigens to develop a model for screening and diagnosis of nasopharyngeal carcinoma (NPC). Samples of 300 nasopharyngeal carcinoma patients and 494 controls, including 294 healthy subjects (HC), 99 non-nasopharyngeal carcinoma cancer patients (NNPC), and 101 patients with benign nasopharyngeal lesions (BNL), were incubated with the EUROLINE Anti-EBV Profile 2, and band intensities were used to establish a risk prediction model. The nasopharyngeal carcinoma risk probability analysis based on the panel of VCAgp125 IgA, EBNA-1 IgA, EA-D IgA, EBNA-1 IgG, EAD IgG, and VCAp19 IgG displayed the best performance. When using 26.1% as the cutoff point in ROC analysis, the AUC value and sensitivity/specificity were 0.951 and 90.7%/86.2%, respectively, in nasopharyngeal carcinoma and all controls. In nasopharyngeal carcinoma and controls without the non-nasopharyngeal carcinoma and BNL groups, the AUC value and sensitivity/specificity were 0.957 and 90.7%/88.1%, respectively. The diagnostic specificity and sensitivity of the EUROLINE Anti-EBV Profile 2 assay for both nasopharyngeal carcinoma and early-stage nasopharyngeal carcinoma were higher than that of mono-antibody detection by immune-enzymatic assay and real-time PCR (EBV DNA). In the VCA-IgA-negative group, 82.6% of nasopharyngeal carcinoma patients showed high probability for nasopharyngeal carcinoma, and the negative predictive value was 97.1%. In the VCA-IgA-positive group, 73.3% of healthy subjects showed low probability. The positive predictive value reached 98.2% in this group. The nasopharyngeal carcinoma risk probability value determined by the EUROLINE Anti-EBV Profile 2 might be a suitable tool for nasopharyngeal carcinoma screening. Cancer Prev Res; 10(9); 542-50. ©2017 AACR . ©2017 American Association for Cancer Research.

A rare case of extra-nasopharyngeal angiofibroma of the septum in a female child.

PubMed

Singh, G B; Shukla, S; Kumari, P; Shukla, I

2018-02-01

Extra-nasopharyngeal angiofibroma is a rare but distinct clinical entity, different from juvenile angiofibroma. This clinical record elucidates the only case of extra-nasopharyngeal angiofibroma arising from the septum in a female child, who presented with epistaxis. The histopathological diagnosis was confirmed by immunohistochemistry, and the case was managed surgically with no recurrence. In a female paediatric patient presenting with epistaxis, extra-nasopharyngeal angiofibroma (of the inferior turbinate) is a rare albeit important differential diagnosis, as it challenges the hormonal theory of angiofibroma aetiopathogenesis.

Mucosal innate response stimulation induced by lipopolysaccharide protects against Bordetella pertussis colonization.

PubMed

Errea, A; Moreno, G; Sisti, F; Fernández, J; Rumbo, M; Hozbor, Daniela Flavia

2010-05-01

Non-specific enhancement of the airways innate response has been shown to impair lung infections in several models of infection such diverse as influenza A, Streptococcus pneumoniae, and Aspergillus niger. Our aim was to evaluate whether a similar event could operate in the context of Bordetella pertussis respiratory infection, not only to enrich the knowledge of host-bacteria interaction but also to establish immunological basis for the development of new control strategies against the pathogen. Using a B. pertussis intranasal infection model and coadministration of different TLR agonists at the moment of the infection, we observed that the enhancement of innate response activation, in a TLR4-dependent way, could efficiently impair B. pertussis colonization (P < 0.001). While LPS from different microbial sources were equally effective in promoting this effect, flagellin and poly I:C coadministration, in spite of inducing expression of innate response markers TNFalpha, CXCL2, CXCL10 and IL6, was not effective to prevent B. pertussis colonization. Our results indicate that during the early stage of infection, specific anti-microbial mechanisms triggered by TLR4 stimulation are able to impair B. pertussis colonization. These findings could complement our current view of the role of TLR4-dependent processes that contribute to anti-pertussis immunity.

Evaluation of matrix metalloproteinase-9 expressions in nasopharyngeal carcinoma patients

NASA Astrophysics Data System (ADS)

Farhat; Asnir, R. A.; Yudhistira, A.; Daulay, E. R.; Puspitasari, D.; Yulius, S.

2018-03-01

Nasopharyngeal carcinoma (NPC) is one of head and neck cancer with a poor prognosis because of the position of the tumor adjacent to the skull base and vital structures. Degradation of extracellular matrix that will cause tumor cells to invade surrounding tissues, vascular or lymphatic vessels. One that plays a role in the extracellular matrix degradation process is matrix metalloproteinase-9 (MMP-9). MMP-9 plays a role in tumor invasion process, metastasis and induction of tumor tissue vascularization. To determine the expression of MMP-9 in patients with nasopharyngeal carcinoma, a descriptive study was conducted by examining immunohistochemistry MMP-9 in 30 NPC tissues that had never received radiotherapy, chemotherapy or combination. Frequency distribution of NPC patient mostly in the age group 41-50 years old and 51-60 years were nine people (30.0%); men (73.3%) and non-keratinizing squamous cell carcinoma (53.3%) histopathology type. The overexpression of MMP-9 in patients with nasopharyngeal carcinoma were mostly found in advance stage.

Oral imazalil exposure induces gut microbiota dysbiosis and colonic inflammation in mice.

PubMed

Jin, Cuiyuan; Zeng, Zhaoyang; Fu, Zhengwei; Jin, Yuanxiang

2016-10-01

The fungicide imazalil (IMZ) is used extensively in vegetable and fruit plantations and as a post-harvest treatment to avoid rot. Here, we revealed that ingestion of 25, 50 and 100 mg IMZ kg(-1) body weight for 28 d induced gut microbiota dysbiosis and colonic inflammation in mice. The relative abundance of Bacteroidetes, Firmicutes and Actinobacteria in the cecal contents decreased significantly after exposure to 100 mg kg(-1) IMZ for 28 d. In feces, the relative abundance in Bacteroidetes, Firmicutes and Actinobacteria decreased significantly after being exposed to 100 mg kg(-1) IMZ for 1, 14 and 7 d, respectively. High throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene revealed a significant reduction in the richness and diversity of microbiota in cecal contents and feces of IMZ-treated mice. Operational taxonomic units (OTUs) analysis identified 49.3% of OTUs changed in cecal contents, while 55.6% of OTUs changed in the feces after IMZ exposure. Overall, at the phylum level, the relative abundance of Firmicutes, Proteobacteria and Actinobacteria increased and that of Bacteroidetes decreased in IMZ-treated groups. At the genus level, the abundance of Lactobacillus and Bifidobacterium decreased while those of Deltaproteobacteria and Desulfovibrio increased in response to IMZ exposure. In addition, it was observed that IMZ exposure could induce colonic inflammation characterized by infiltration of inflammatory cells, elevated levels of lipocalin-2 (lcn-2) in the feces, and increased mRNA levels of Tnf-α, IL-1β, IL-22 and IFN-γ in the colon. Our findings strongly suggest that ingestion of IMZ has some risks to human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts.

PubMed

Tsang, Chi Man; Cheung, Yuk Chun; Lui, Vivian Wai-Yan; Yip, Yim Ling; Zhang, Guitao; Lin, Victor Weitao; Cheung, Kenneth Chat-Pan; Feng, Yibin; Tsao, Sai Wah

2013-12-31

Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC.

Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts

PubMed Central

2013-01-01

Background Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. Methods In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Results Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Conclusions Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC. PMID:24380387

Analysis of factors in successful nasal endoscopic resection of nasopharyngeal angiofibroma.

PubMed

Ye, Dong; Shen, Zhisen; Wang, Guoli; Deng, Hongxia; Qiu, Shijie; Zhang, Yuna

2016-01-01

Endoscopic resection of nasopharyngeal angiofibroma is less traumatic, causes less bleeding, and provides a good curative effect. Using pre-operative embolization and controlled hypotension, reasonable surgical strategies and techniques lead to successful resection tumors of a maximum Andrews-Fisch classification stage of III. To investigate surgical indications, methods, surgical technique, and curative effects of transnasal endoscopic resection of nasopharyngeal angiofibroma, this study evaluated factors that improve diagnosis and treatment, prevent large intra-operative blood loss and residual tumor, and increase the cure rate. A retrospective analysis was performed of the clinical data and treatment programs of 23 patients with nasopharyngeal angiofibroma who underwent endoscopic resection with pre-operative embolization and controlled hypotension. The surgical method applied was based on the size of tumor and extent of invasion. Curative effects were observed. No intra-operative or perioperative complications were observed in 22 patients. Upon removal of nasal packing material 3-7 days post-operatively, one patient experienced heavy bleeding of the nasopharyngeal wound, which was treated compression hemostasis using post-nasal packing. Twenty-three patients were followed up for 6-60 months. Twenty-two patients experienced cure; one patient experienced recurrence 10 months post-operatively, and repeat nasal endoscopic surgery was performed and resulted in cure.

Enhanced sympathetic nerve activity induced by neonatal colon inflammation induces gastric hypersensitivity and anxiety-like behavior in adult rats.

PubMed

Winston, John H; Sarna, Sushil K

2016-07-01

Gastric hypersensitivity (GHS) and anxiety are prevalent in functional dyspepsia patients; their underlying mechanisms remain unknown largely because of lack of availability of live visceral tissues from human subjects. Recently, we demonstrated in a preclinical model that rats subjected to neonatal colon inflammation show increased basal plasma norepinephrine (NE), which contributes to GHS through the upregulation of nerve growth factor (NGF) expression in the gastric fundus. We tested the hypothesis that neonatal colon inflammation increases anxiety-like behavior and sympathetic nervous system activity, which upregulates the expression of NGF to induce GHS in adult life. Chemical sympathectomy, but not adrenalectomy, suppressed the elevated NGF expression in the fundus muscularis externa and GHS. The measurement of heart rate variability showed a significant increase in the low frequency-to-high frequency ratio in GHS vs. the control rats. Stimulus-evoked release of NE from the fundus muscularis externa strips was significantly greater in GHS than in the control rats. Tyrosine hydroxylase expression was increased in the celiac ganglia of the GHS vs. the control rats. We found an increase in trait but not stress-induced anxiety-like behavior in GHS rats in an elevated plus maze. We concluded that neonatal programming triggered by colon inflammation upregulates tyrosine hydroxylase in the celiac ganglia, which upregulates the release of NE in the gastric fundus muscularis externa. The increase of NE release from the sympathetic nerve terminals concentration dependently upregulates NGF, which proportionately increases the visceromotor response to gastric distention. Neonatal programming concurrently increases anxiety-like behavior in GHS rats. Copyright © 2016 the American Physiological Society.

Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs Required for Host Cell Colonization

PubMed Central

Capel, Elena; Zomer, Aldert L.; Nussbaumer, Thomas; Bole, Christine; Izac, Brigitte; Frapy, Eric; Meyer, Julie; Bouzinba-Ségard, Haniaa; Bille, Emmanuelle; Jamet, Anne; Cavau, Anne; Letourneur, Franck; Bourdoulous, Sandrine; Rattei, Thomas; Coureuil, Mathieu

2016-01-01

ABSTRACT Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia, affecting infants and adults worldwide. N. meningitidis is also a common inhabitant of the human nasopharynx and, as such, is highly adapted to its niche. During bacteremia, N. meningitidis gains access to the blood compartment, where it adheres to endothelial cells of blood vessels and causes dramatic vascular damage. Colonization of the nasopharyngeal niche and communication with the different human cell types is a major issue of the N. meningitidis life cycle that is poorly understood. Here, highly saturated random transposon insertion libraries of N. meningitidis were engineered, and the fitness of mutations during routine growth and that of colonization of endothelial and epithelial cells in a flow device were assessed in a transposon insertion site sequencing (Tn-seq) analysis. This allowed the identification of genes essential for bacterial growth and genes specifically required for host cell colonization. In addition, after having identified the small noncoding RNAs (sRNAs) located in intergenic regions, the phenotypes associated with mutations in those sRNAs were defined. A total of 383 genes and 8 intergenic regions containing sRNA candidates were identified to be essential for growth, while 288 genes and 33 intergenic regions containing sRNA candidates were found to be specifically required for host cell colonization. PMID:27486197

Korean Solar Salt Ameliorates Colon Carcinogenesis in an AOM/DSS-Induced C57BL/6 Mouse Model.

PubMed

Ju, Jaehyun; Kim, Yeung-Ju; Park, Eui Seong; Park, Kun-Young

2017-06-01

The effects of Korean solar salt on an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer C57BL/6 mouse model were studied. Korean solar salt samples (SS-S, solar salt from S salt field; SS-Yb, solar salt from Yb salt field), nine-time-baked bamboo salt (BS-9x, made from SS-Yb), purified salt (PS), and SS-G (solar salt from Guérande, France) were orally administered at a concentration of 1% during AOM/DSS colon cancer induction, and compared for their protective effects during colon carcinogenesis in C57BL/6 mice. SS-S and SS-Yb suppressed colon length shortening and tumor counts in mouse colons. Histological evaluation by hematoxylin and eosin staining also revealed suppression of tumorigenesis by SS-S. Conversely, PS and SS-G did not show a similar suppressive efficacy as Korean solar salt. SS-S and SS-Yb promoted colon mRNA expression of an apoptosis-related factor and cell-cycle-related gene and suppressed pro-inflammatory factor. SS-Yb baked into BS-9x further promoted these anti-carcinogenic efficacies. Taken together, the results indicate that Korean solar salt, especially SS-S and SS-Yb, exhibited anti-cancer activity by modulating apoptosis- and inflammation-related gene expression during colon carcinogenesis in mice, and bamboo salt baked from SS-Yb showed enhanced anti-cancer functionality.

δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.

PubMed

Chen, Jayson X; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S

2017-01-01

Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T, and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Inactivation of PMS2 gene by promoter methylation in nasopharyngeal carcinoma].

PubMed

Ni, H F; Jiang, B; Zhou, Z; Li, Y; Yuan, X Y; Cao, X L; Huang, G W

2016-11-23

Objective: To investigate the inactivation of PMS2 gene mediated by promoter methylation and its regulatory mechanism in nasopharyngeal carcinoma (NPC). Methods: Fifty-four NPC tissues, 16 normal nasopharyngeal epithelia (NNE), 5 NPC cell lines (CNE1, CNE2, TWO3, HNE1 and HONE1) and 1 normal nasopharyngeal epithelial cell line (NP69) were collected.Methylation-specific PCR (MSP) was used to detect the PMS2 promoter methylation, semi-quantitative reverse transcription PCR (qRT-PCR) was applied to determine its mRNA expression, and immunohistochemistry (IHC) was used to detect the protein expression of PMS2. The expressions of PMS2 mRNA in CNE1 and CNE2 cells before and after treated with methyltransferase inhibitor 5-aza-2-deoxycytidine were analyzed by qRT-PCR. The impact of methylation and demethylation on the mRNA expression of PMS2, and the association of mRNA and protein expression of PMS2 with clinicopathological features of nasopharyngeal cancer were analyzed. Results: Methylation of PMS2 gene was detected in all of the five NPC cell lines, but not in normal nasopharyngeal epithelial NP69 cells. The methylation rate of PMS2 gene in NPC tissues was 63% (34/54), significantly higher than that of the normal nasopharyngeal epithelia (0/16, P <0.001). The expression levels of PMS2 mRNA and protein were significantly down-regulated in the 54 NPC tissues when compared with those in the 16 NNE tissues ( P <0.001), and were also significantly lower in the 34 methylated NPC tissues than those in the 20 unmethylated NPC tissues ( P <0.001). After treatment with 5-aza-2-deoxycytidine, the expression of PMS2 mRNA was restored in the CNE1 and CNE2 cells.However, the expressions of PMS2 mRNA and protein were not significantly correlated with patients' age, gender, TNM stage, histopathologic type or lymph node metastasis ( P >0.05 for all). Conclusions: Promoter methylation-mediated inactivation of PMS2 gene participates in carcinogenesis and development of NPC. PMS2 may be

P38 mitogen-activated protein kinase (p38 MAPK) overexpression in clinical staging of nasopharyngeal carcinoma

NASA Astrophysics Data System (ADS)

Farhat; Asnir, R. A.; Yudhistira, A.; Daulay, E. R.; Muzakkir, M. M.; Yulius, S.

2018-03-01

Molecular biological research on nasopharyngeal carcinoma has been widely practiced, such as VEGF, EGFR, COX-2 expression and so on. MAPK plays a role in cell growth such as proliferation, differentiation, and apoptosis, primarily contributing to gene expression, where p38 MAPK pathway mostly associate with anti-apoptosis and cause cell transformation. The aim of this study is to determine the expression of p38 MAPK in clinical stage of nasopharyngeal carcinoma so that the result can be helpful in prognosis and adjunctive therapy in nasopharyngeal carcinoma. The research design is descriptive. It was done in THT- KL Department of FK USU/RSUP Haji Adam Malik, Medan and Pathology Anatomical Department of FK USU. The study was conducted from December 2011 to May 2012. The Samples are all patients who diagnosed with nasopharyngeal carcinoma in oncology division of Otorhinolaryngology Department. p38 MAPK overexpression was found in 21 samples (70%) from 30 nasopharyngeal carcinoma samples. The elevated of p38 MAPK expression most found on T4 by eight samples (38.1%), N3 lymph node group by nine samples (42.9%), stage IV of clinical staging is as many as 15 samples (71.4%). p38 MAPK most expressed in stage IV clinical staging of patients with nasopharyngeal carcinoma.

Nasopharyngeal Microbiome Diversity Changes over Time in Children with Asthma.

PubMed

Pérez-Losada, Marcos; Alamri, Lamia; Crandall, Keith A; Freishtat, Robert J

2017-01-01

The nasopharynx is a reservoir for pathogens associated with respiratory illnesses such as asthma. Next-generation sequencing (NGS) has been used to characterize the nasopharyngeal microbiome of infants and adults during health and disease; less is known, however, about the composition and temporal dynamics (i.e., longitudinal variation) of microbiotas from children and adolescents. Here we use NGS technology to characterize the nasopharyngeal microbiomes of asthmatic children and adolescents (6 to 18 years) and determine their stability over time. Two nasopharyngeal washes collected 5.5 to 6.5 months apart were taken from 40 children and adolescents with asthma living in the Washington D.C. area. Sequence data from the 16S-V4 rRNA gene region (~250 bp) were collected from the samples using the MiSeq platform. Raw data were processed in mothur (SILVA123 reference database) and Operational Taxonomic Units (OTU)-based alpha- and beta-diversity metrics were estimated. Relatedness among samples was assessed using PCoA ordination and Procrustes analyses. Differences in microbial diversity and taxon mean relative proportions were assessed using linear mixed effects models. Core microbiome analyses were also performed to identify stable and consistent microbes of the nasopharynx. A total of 2,096,584 clean 16S sequences corresponding to an average of 167 OTUs per sample were generated. Representatives of Moraxella*, Staphylococcus*, Dolosigranulum, Corynebacterium, Prevotella, Streptococcus*, Haemophilus*, Fusobacterium* and a Neisseriaceae genus accounted for 86% of the total reads. These nine genera have been previously found in the nasopharynxes of both infants and adults, but in different proportions. OTUs from the five genera highlighted (*) above defined the nasopharyngeal core microbiome at the 95% level. No significant differences in alpha- and beta-diversity were observed between seasons, but bacterial mean relative proportions of Haemophilus, Moraxella

The inflammatory mediator leukotriene D{sub 4} induces subcellular β-catenin translocation and migration of colon cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salim, Tavga; Sand-Dejmek, Janna; Section of Surgery, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö

2014-02-15

The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D{sub 4} (LTD{sub 4}) exerts its effects through the CysLT{sub 1} receptor. We previously reported an upregulation of CysLT{sub 1}R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD{sub 4} on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD{sub 4} stimulation led to anmore » increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD{sub 4} significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD{sub 4} can be blocked by the inhibition of CysLT{sub 1}R. Furthermore, LTD{sub 4} induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT{sub 1} and the Wnt/β-catenin pathway. In conclusion, LTD{sub 4}, which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. - Highlights: • Leukotriene D{sub 4} (LTD{sub 4}) lowers membrane β-catenin but increases nuclear β-catenin levels in colon cancer cells. • In agreement, LTD{sub 4} triggers inactivation of GSK-3β, activation of TCF/LEF and increased expression of Cyclin D1 and c-Myc. • LTD{sub 4} also caused a significant reduction in the expression of E-cadherin and an increased migration of colon cancer cells.« less

The protective role of Lychnophora ericoides Mart. (Brazilian arnica) in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis.

PubMed

Fernandes, Cleverson Rodrigues; Turatti, Aline; Gouvea, Dayana Rubio; Gobbo-Neto, Leonardo; Diniz, Andrea; Ribeiro-Silva, Alfredo; Lopes, Norberto Peporine; Garcia, Sérgio Britto

2011-01-01

Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.

Incidence of nasopharyngeal carcinoma in Chinese immigrants, compared with Chinese in China and South East Asia: review.

PubMed

Yu, W M; Hussain, S S M

2009-10-01

To evaluate the literature and to compare published data on age-standardised incidence rates of nasopharyngeal carcinoma in Chinese people living in and outside China. Systematic review of incidence rate studies and statistical incidence data concerning nasopharyngeal carcinoma in Chinese populations from 1960 to 2008. Sixteen papers were identified from the PubMed, Embase and Scopus electronic databases and from a hand search of the reference lists of the retrieved papers. Further searches for raw data on age-specific and age-standardised incidence rates of nasopharyngeal carcinoma were conducted. Textbooks on relevant subjects were referred to for background information. A total of 19 papers met the inclusion criteria. Seven studies included raw data on age-specific and age-standardised incidence rates of nasopharyngeal carcinoma in Chinese people. Twelve other studies reported on changes in the incidence of nasopharyngeal carcinoma in Chinese populations in selected countries or regions. Studies on age-specific and age-standardised rates obtained data from individual registries. Studies on incidence rates obtained data from hospital records, cancer notifications (from all sections of the medical profession), pathology records and death certificates. The results showed a decline in age-standardised incidence rates of nasopharyngeal carcinoma in Chinese immigrant populations, compared with Chinese people in China. There was also a trend towards decreasing incidence the further the population had immigrated. Thus, the incidence of nasopharyngeal carcinoma in Singaporean Chinese was higher than that in Hawaiian Chinese, and that in Hawaiian Chinese was higher than that in Californian Chinese. This review found a decreasing trend in the incidence of nasopharyngeal carcinoma in Chinese migrants living in countries with a low risk of the disease.

Neurological and cellular regulation of visceral hypersensitivity induced by chronic stress and colonic inflammation in rats.

PubMed

Chen, J; Winston, J H; Sarna, S K

2013-09-17

The role of inflammation in inducing visceral hypersensitivity (VHS) in ulcerative colitis patients remains unknown. We tested the hypothesis that acute ulcerative colitis-like inflammation does not induce VHS. However, it sets up molecular conditions such that chronic stress following inflammation exaggerates single-unit afferent discharges to colorectal distension. We used dextran sodium sulfate (DSS) to induce ulcerative colitis-like inflammation and a 9-day heterotypic chronic stress protocol in rats. DSS upregulated Nav1.8 mRNA in colon-responsive dorsal root ganglion (DRG) neurons, TRPV1 in colonic muscularis externae (ME) and BDNF in spinal cord without affecting the spike frequency in spinal afferents or VMR to CRD. By contrast, chronic stress did not induce inflammation but it downregulated Kv1.1 and Kv1.4 mRNA in DRG neurons, and upregulated TRPA1 and nerve growth factor in ME, which mediated the increase of spike frequency and VMR to CRD. Chronic stress following inflammation exacerbated spike frequency in spinal afferent neurons. TRPA1 antagonist suppressed the sensitization of afferent neurons. DSS-inflammation did not affect the composition or excitation thresholds of low-threshold and high-threshold fibers. Chronic stress following inflammation increased the percent composition of high-threshold fibers and lowered the excitation threshold of both types of fibers. We conclude that not all types of inflammation induce VHS, whereas chronic stress induces VHS in the absence of inflammation. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway.

PubMed

Zeriouh, Wafa; Nani, Abdelhafid; Belarbi, Meriem; Dumont, Adélie; de Rosny, Charlotte; Aboura, Ikram; Ghanemi, Fatima Zahra; Murtaza, Babar; Patoli, Danish; Thomas, Charles; Apetoh, Lionel; Rébé, Cédric; Delmas, Dominique; Khan, Naim Akhtar; Ghiringhelli, François; Rialland, Mickael; Hichami, Aziz

2017-01-01

Dietary polyphenols, derived from natural products, have received a great interest for their chemopreventive properties against cancer. In this study, we investigated the effects of phenolic extract of the oleaster leaves (PEOL) on tumor growth in mouse model and on cell death in colon cancer cell lines. We assessed the effect of oleaster leaf infusion on HCT116 (human colon cancer cell line) xenograft growth in athymic nude mice. We observed that oleaster leaf polyphenol-rich infusion limited HCT116 tumor growth in vivo. Investigations of PEOL on two human CRC cell lines showed that PEOL induced apoptosis in HCT116 and HCT8 cells. We demonstrated an activation of caspase-3, -7 and -9 by PEOL and that pre-treatment with the pan-caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), prevented PEOL-induced cell death. We observed an involvement of the mitochondrial pathway in PEOL-induced apoptosis evidenced by reactive oxygen species (ROS) production, a decrease of mitochondrial membrane potential, and cytochrome c release. Increase in intracellular Ca2+ concentration induced by PEOL represents the early event involved in mitochondrial dysfunction, ROS-induced endoplasmic reticulum (ER) stress and apoptosis induced by PEOL, as ruthenium red, an inhibitor of mitochondrial calcium uptake inhibited apoptotic effect of PEOL, BAPTA/AM inhibited PEOL-induced ROS generation and finally, N-acetyl-L-cysteine reversed ER stress and apoptotic effect of PEOL. These results demonstrate that polyphenols from oleaster leaves might have a strong potential as chemopreventive agent in colorectal cancer.

Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation

PubMed Central

Raisch, Jennifer; Buc, Emmanuel; Bonnet, Mathilde; Sauvanet, Pierre; Vazeille, Emilie; de Vallée, Amélie; Déchelotte, Pierre; Darcha, Claude; Pezet, Denis; Bonnet, Richard; Bringer, Marie-Agnès; Darfeuille-Michaud, Arlette

2014-01-01

AIM: To provide further insight into the characterization of mucosa-associated Escherichia coli (E. coli) isolated from the colonic mucosa of cancer patients. METHODS: Phylogroups and the presence of cyclomodulin-encoding genes of mucosa-associated E. coli from colon cancer and diverticulosis specimens were determined by PCR. Adhesion and invasion experiments were performed with I-407 intestinal epithelial cells using gentamicin protection assay. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression in T84 intestinal epithelial cells was measured by enzyme-linked immunosorbent assay and by Western Blot. Gut colonization, inflammation and pro-carcinogenic potential were assessed in a chronic infection model using CEABAC10 transgenic mice. Cell proliferation was analyzed by real-time mRNA quantification of PCNA and immunohistochemistry staining of Ki67. RESULTS: Analysis of mucosa-associated E. coli from colon cancer and diverticulosis specimens showed that whatever the origin of the E. coli strains, 86% of cyclomodulin-positive E. coli belonged to B2 phylogroup and most harbored polyketide synthase (pks) island, which encodes colibactin, and/or cytotoxic necrotizing factor (cnf) genes. In vitro assays using I-407 intestinal epithelial cells revealed that mucosa-associated B2 E. coli strains were poorly adherent and invasive. However, mucosa-associated B2 E. coli similarly to Crohn’s disease-associated E. coli are able to induce CEACAM6 expression in T84 intestinal epithelial cells. In addition, in vivo experiments using a chronic infection model of CEACAM6 expressing mice showed that B2 E. coli strain 11G5 isolated from colon cancer is able to highly persist in the gut, and to induce colon inflammation, epithelial damages and cell proliferation. CONCLUSION: In conclusion, these data bring new insights into the ability of E. coli isolated from patients with colon cancer to establish persistent colonization, exacerbate inflammation and

The pertussis hypothesis: Bordetella pertussis colonization in the pathogenesis of Alzheimer's disease.

PubMed

Rubin, Keith; Glazer, Steven

2017-02-01

While a number of endogenous risk factors including age and genetics are established for Alzheimer's disease (AD), identification of acquired, potentially preventable or treatable causes, remains limited. In this paper, we review three epidemiologic case studies and present extensive biologic, immunologic and anatomic evidence to support a novel hypothesis that Bordetella pertussis (BP), the bacterium better known to cause whooping cough, is an important potential cause of AD. Cross-cultural documentation of nasopharyngeal subclinical BP colonization reflecting BP-specific mucosal immunodeficiency, proximate anatomy of intranasal mucosal surfaces to central nervous system (CNS) olfactory pathways, and mechanisms by which BP and BP toxin account for all hallmark pathology of AD are reviewed, substantiating biologic plausibility. Notably, respiratory BP infection and BP toxin secreted from subclinical BP colonization can account for the initiation and accumulation of amyloid β plaques and tau tangles. Additional mechanisms consistent with the immunobiologic effects of subclinical BP colonization include microglial activation and inflammation, atrophy and neurodegeneration, excitotoxicity, distinctive anatomic distribution and sequential spread of disease, impaired glucose utilization, and other characteristic CNS pathology of AD. We conclude by assessing the evidence for causation against the Bradford Hill criteria, and advocate for further investigation into the potential role of BP in the etiology of AD. Copyright © 2016 The Author(s). Published by Elsevier GmbH.. All rights reserved.

Pharmacological identification of β-adrenoceptor subtypes mediating isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle.

PubMed

Chino, Daisuke; Sone, Tomoyo; Yamazaki, Kumi; Tsuruoka, Yuri; Yamagishi, Risa; Shiina, Shunsuke; Obara, Keisuke; Yamaki, Fumiko; Higai, Koji; Tanaka, Yoshio

2018-01-01

Object We aimed to identify the β-adrenoceptor (β-AR) subtypes involved in isoprenaline-induced relaxation of guinea pig colonic longitudinal smooth muscle using pharmacological and biochemical approaches. Methods Longitudinal smooth muscle was prepared from the male guinea pig ascending colon and contracted with histamine prior to comparing the relaxant responses to three catecholamines (isoprenaline, adrenaline, and noradrenaline). The inhibitory effects of subtype-selective β-AR antagonists on isoprenaline-induced relaxation were then investigated. Results The relaxant potencies of the catecholamines were ranked as: isoprenaline > noradrenaline ≈ adrenaline, whereas the rank order was isoprenaline > noradrenaline > adrenaline in the presence of propranolol (a non-selective β-AR antagonist; 3 × 10 -7 M). Atenolol (a selective β 1 -AR antagonist; 3 × 10 -7 -10 -6  M) acted as a competitive antagonist of isoprenaline-induced relaxation, and the pA 2 value was calculated to be 6.49 (95% confidence interval: 6.34-6.83). The relaxation to isoprenaline was not affected by ICI-118,551 (a selective β 2 -AR antagonist) at 10 -9 -10 -8  M, but was competitively antagonized by 10 -7 -3 × 10 -7  M, with a pA 2 value of 7.41 (95% confidence interval: 7.18-8.02). In the presence of propranolol (3 × 10 -7 M), the relaxant effect of isoprenaline was competitively antagonized by bupranolol (a non-selective β-AR antagonist), with a pA 2 value of 5.90 (95% confidence interval: 5.73-6.35). Conclusion These findings indicated that the β-AR subtypes involved in isoprenaline-induced relaxation of colonic longitudinal guinea pig muscles are β 1 -AR and β 3 -AR.

The steroidal Na+/K+ ATPase inhibitor 3-[(R)-3-pyrrolidinyl]oxime derivative (3-R-POD) induces potent pro-apoptotic responses in colonic tumor cells.

PubMed

Alkahtani, Saad Hussin

2014-06-01

Recently, potent anticancer actions of the steroidal Na(+)/K(+) ATPase inhibitor 3-[(R)-3-pyrrolidinyl]oxime derivative 3 (3-R-POD) have been reported for multiple cell lines, including prostate and lung cancer cells. In the present study, the anticancer action of 3-R-POD was addressed in colonic tumor cells. Treatment of Caco2 colonic tumor cells with increasing concentrations of 3-R-POD induced potent, dose-dependent inhibition of cell growth as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the APOpercentage apoptosis assay revealed significant pro-apoptotic responses, suggesting that the anticancer activity of this steroidal Na(+)/K(+) ATPase inhibitor in colonic tumors takes places mainly through the induction of strong pro-apoptotic effects. Focussing on the molecular mechanism that may regulate these interactions, 3-R-POD was shown to induce significant early actin re-organization and late Protein Kinase B (AKT) de-phosphorylation. Finally, the 3-R-POD-induced inhibition of cell growth and early actin reorganization in colonic cancer cells remained unchanged when cells were pre-treated with pertussis toxin, thus excluding possible interactions of this inhibitor with G-coupled receptors. These results indicate that 3-R-POD induces potent pro-apoptotic responses in colonic tumor cells governed by actin re-organization and inhibition of AKT pro-survival signaling. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Rosmarinic acid suppresses colonic inflammation in dextran sulphate sodium (DSS)-induced mice via dual inhibition of NF-κB and STAT3 activation.

PubMed

Jin, Bo-Ram; Chung, Kyung-Sook; Cheon, Se-Yun; Lee, Minho; Hwang, Soonjae; Noh Hwang, Sam; Rhee, Ki-Jong; An, Hyo-Jin

2017-04-06

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disorder of the colon. Although UC is generally treated with anti-inflammatory drugs or immunosuppressants, most of these treatments often prove to be inadequate. Rosmarinic acid (RA) is a phenolic ester included in various medicinal herbs such as Salvia miltiorrhiz and Perilla frutescens. Although RA has many biological and pharmacological activities, the anti-inflammatory effect of RA in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and underlying molecular mechanism of RA in mice with dextran sulphate sodium (DSS)-induced colitis. In the DSS-induced colitis model, RA significantly reduced the severity of colitis, as assessed by disease activity index (DAI) scores, colonic damage, and colon length. In addition, RA resulted in the reduction of the inflammatory-related cytokines, such as IL-6, IL-1β, and IL-22, and protein levels of COX-2 and iNOS in mice with DSS-induced colitis. Furthermore, RA effectively and pleiotropically inhibited nuclear factor-kappa B and signal transducer and activator of transcription 3 activation, and subsequently reduced the activity of pro-survival genes that depend on these transcription factors. These results demonstrate that RA has an ameliorative effect on colonic inflammation and thus a potential therapeutic role in colitis.

Massive juvenile nasopharyngeal angiofibroma: ode to the open surgical approach.

PubMed

Meher, Ravi; Arora, Nikhil; Bhargava, Eishaan Kamta; Juneja, Ruchika

2017-08-01

The management of juvenile nasopharyngeal angiofibroma has undergone a significant evolution, with more surgeons moving towards the minimal invasive endoscopic approaches. Although considered the standard of care by most, an endoscopic approach may not be sufficient for extensive tumours, as exemplified by the current case of a young man presenting with the largest juvenile nasopharyngeal angiofibroma described in English literature until the present that was eventually excised via an anterior external approach. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Juvenile nasopharyngeal angiofibroma--a rare case of primary orbital development.

PubMed

Moschos, M; Demetra, A; Kontogeorgos, G

1998-08-01

To present a rare case of juvenile nasopharyngeal angiofibroma invading the ophthalmic orbit. The CT scan examination and the ultrasound tomography revealed the existence of a homogeneous solid mass causing distention and erosion of the nasal wall as well as dislocation of the ocular bulbus. The patient was operated, the mass was carefully liberated from its synechiae and it was totally excised with its capsule. A rare case of juvenile nasopharyngeal angiofibroma invading the orbit is presented. The tumor was totally excized and the patient is five years after the operation in good general health without recurrence of the tumor.

The protective effect of supplemental calcium on colonic permeability depends on a calcium phosphate-induced increase in luminal buffering capacity.

PubMed

Schepens, Marloes A A; ten Bruggencate, Sandra J M; Schonewille, Arjan J; Brummer, Robert-Jan M; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M J

2012-04-01

An increased intestinal permeability is associated with several diseases. Previously, we have shown that dietary Ca decreases colonic permeability in rats. This might be explained by a calcium-phosphate-induced increase in luminal buffering capacity, which protects against an acidic pH due to microbial fermentation. Therefore, we investigated whether dietary phosphate is a co-player in the effect of Ca on permeability. Rats were fed a humanised low-Ca diet, or a similar diet supplemented with Ca and containing either high, medium or low phosphate concentrations. Chromium-EDTA was added as an inert dietary intestinal permeability marker. After dietary adaptation, short-chain fructo-oligosaccharides (scFOS) were added to all diets to stimulate fermentation, acidify the colonic contents and induce an increase in permeability. Dietary Ca prevented the scFOS-induced increase in intestinal permeability in rats fed medium- and high-phosphate diets but not in those fed the low-phosphate diet. This was associated with higher faecal water cytotoxicity and higher caecal lactate levels in the latter group. Moreover, food intake and body weight during scFOS supplementation were adversely affected by the low-phosphate diet. Importantly, luminal buffering capacity was higher in rats fed the medium- and high-phosphate diets compared with those fed the low-phosphate diet. The protective effect of dietary Ca on intestinal permeability is impaired if dietary phosphate is low. This is associated with a calcium phosphate-induced increase in luminal buffering capacity. Dragging phosphate into the colon and thereby increasing the colonic phosphate concentration is at least part of the mechanism behind the protective effect of Ca on intestinal permeability.

Juvenile Nasopharyngeal Angiofibroma.

PubMed

Bakshi, Satvinder S; Bhattacharjee, Sumita

2016-08-01

A 9 year old male presented with nasal obstruction and recurrent, unprovoked epistaxis for 1 week. Imaging revealed a highly vascular mass in the nasopharynx. The feeding vessels were subsequently embolized and the mass was removed completely. Juvenile nasopharyngeal angiofibroma is a benign but locally invasive tumor accounting for about 0.05% of all head and neck tumors. Patients usually present with nasal obstruction and epistaxis. The tumor can however be extensive on presentation with intra orbital and intra cranial extension. The treatment is surgical removal of the tumor and the approach depends on the size of the tumor by either endoscopic or open approach.

Microarray Analyses of Genes Differentially Expressed by Diet (Black Beans and Soy Flour) during Azoxymethane-Induced Colon Carcinogenesis in Rats.

PubMed

Rondini, Elizabeth A; Bennink, Maurice R

2012-01-01

We previously demonstrated that black bean (BB) and soy flour (SF)-based diets inhibit azoxymethane (AOM)-induced colon cancer. The objective of this study was to identify genes altered by carcinogen treatment in normal-appearing colonic mucosa and those attenuated by bean feeding. Ninety-five male F344 rats were fed control (AIN) diets upon arrival. At 4 and 5 weeks, rats were injected with AOM (15 mg/kg) or saline and one week later administered an AIN, BB-, or SF-based diet. Rats were sacrificed after 31 weeks, and microarrays were conducted on RNA isolated from the distal colonic mucosa. AOM treatment induced a number of genes involved in immunity, including several MHC II-associated antigens and innate defense genes (RatNP-3, Lyz2, Pla2g2a). BB- and SF-fed rats exhibited a higher expression of genes involved in energy metabolism and water and sodium absorption and lower expression of innate (RatNP-3, Pla2g2a, Tlr4, Dmbt1) and cell cycle-associated (Cdc2, Ccnb1, Top2a) genes. Genes involved in the extracellular matrix (Col1a1, Fn1) and innate immunity (RatNP-3, Pla2g2a) were induced by AOM in all diets, but to a lower extent in bean-fed animals. This profile suggests beans inhibit colon carcinogenesis by modulating cellular kinetics and reducing inflammation, potentially by preserving mucosal barrier function.

Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

PubMed Central

Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

2016-01-01

Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

Active Ingredients of Hange-shashin-to, Baicalelin and 6-Gingerol, Inhibit 5-Fluorouracil-Induced Upregulation of CXCL1 in the Colon to Attenuate Diarrhea Development.

PubMed

Sakai, Hiroyasu; Tabata, Shoko; Kimura, Minami; Yabe, Saori; Isa, Yosuke; Kai, Yuki; Sato, Fumiaki; Yumoto, Tetsuro; Miyano, Kanako; Narita, Minoru; Uezono, Yasuhito

2017-01-01

5-Fluorouracil (5-FU) is widely used as an anti cancer drug and is known to cause severe diarrhea. Recently we suggested that levels of chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophil recruitment in the colonic mucosa were drastically increased by the 5-FU administration in mice. Hange-shashin-to (HST) is prescribed in Japan for treat gastritis, stomatitis, and inflammatory diarrhea. We therefore examined the effects of HST and its active ingredients on 5-FU-induced CXCL1 upregulation in cultured colon tissue, and also examined the effects of HST on 5-FU-induced diarrhea development in the mouse. The distal colon isolated from the mouse was incubated with 5-FU and HST. Mice were given 5-FU (50 mg/kg, intraperitoneally (i.p.)) daily for four days. HST (300 mg/kg, per os (p.o.)) was administered 30 min before mice received 5-FU. mRNA levels of CXCL1 in the colon were examined using quantitative RT-PCR. 5-FU enhanced CXCL1 mRNA in the colon but the effect by 5-FU was markedly suppressed by application of HST and its active ingredients, baicalein and 6-gingerol. Nuclear factor kappa B (NF-κB) was activated by 5-FU treatment in cultured colon tissue, which was also suppressed by HST and the combination of baicalein and 6-gingerol. Furthermore, HST reduced 5-FU-induced diarrhea development. Under such experimental condition, CXCL1 gene, protein levels of neutrophil elastase and myeloperoxidase upregulation induced by 5-FU in the colon was attenuated by HST. These findings suggest that HST, especially baicalein and 6-gingerol, prevent the development of neutrophil recruitment and diarrhea by the inhibition of NF-κB activity.

Cell proliferation in dimethylhydrazine-induced colonic adenocarcinomata following cytotoxic drug treatment.

PubMed

Tutton, P J; Barkla, D H

1978-08-25

A stathmokinetic technique was used to study cell proliferation in dimethylhydrazine-induced adenocarcinomata of rat colon following treatment with cytotoxic drugs. The rate of cell division was significantly increased three days after treatment with 5,7-dihydroxytryptamine and seven days after treatment with 5-fluorouracil. Acceleration of tumour cell proliferation following 5,7-dihydroxytryptamine treatment was inhibited by treating animals with the antiseritoninergic drug Xylamidine Tosylate. Acceleration of tumour cell proliferation following 5-fluorouracil treatment was inhibited by treating animals either with the antiseritoninergic drug BW501 or with the histamine H2-receptor blocking drug Cimetidine.

Butyrate-Induced Transcriptional Changes in Human Colonic Mucosa

PubMed Central

Vanhoutvin, Steven A. L. W.; Troost, Freddy J.; Hamer, Henrike M.; Lindsey, Patrick J.; Koek, Ger H.; Jonkers, Daisy M. A. E.; Kodde, Andrea; Venema, Koen; Brummer, Robert J. M.

2009-01-01

Background Fermentation of dietary fiber in the colon results in the production of short chain fatty acids (mainly propionate, butyrate and acetate). Butyrate modulates a wide range of processes, but its mechanism of action is mostly unknown. This study aimed to determine the effects of butyrate on the transcriptional regulation of human colonic mucosa in vivo. Methodology/Principal Findings Five hundred genes were found to be differentially expressed after a two week daily butyrate administration with enemas. Pathway analysis showed that the butyrate intervention mainly resulted in an increased transcriptional regulation of the pathways representing fatty acid oxidation, electron transport chain and oxidative stress. In addition, several genes associated with epithelial integrity and apoptosis, were found to be differentially expressed after the butyrate intervention. Conclusions/Significance Colonic administration of butyrate in concentrations that can be achieved by consumption of a high-fiber diet enhances the maintenance of colonic homeostasis in healthy subjects, by regulating fatty acid metabolism, electron transport and oxidative stress pathways on the transcriptional level and provide for the first time, detailed molecular insight in the transcriptional response of gut mucosa to butyrate. PMID:19707587

Colonization-Induced Host-Gut Microbial Metabolic Interaction

PubMed Central

Claus, Sandrine P.; Ellero, Sandrine L.; Berger, Bernard; Krause, Lutz; Bruttin, Anne; Molina, Jérôme; Paris, Alain; Want, Elizabeth J.; de Waziers, Isabelle; Cloarec, Olivier; Richards, Selena E.; Wang, Yulan; Dumas, Marc-Emmanuel; Ross, Alastair; Rezzi, Serge; Kochhar, Sunil; Van Bladeren, Peter; Lindon, John C.; Holmes, Elaine; Nicholson, Jeremy K.

2011-01-01

The gut microbiota enhances the host’s metabolic capacity for processing nutrients and drugs and modulate the activities of multiple pathways in a variety of organ systems. We have probed the systemic metabolic adaptation to gut colonization for 20 days following exposure of axenic mice (n = 35) to a typical environmental microbial background using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy to analyze urine, plasma, liver, kidney, and colon (5 time points) metabolic profiles. Acquisition of the gut microbiota was associated with rapid increase in body weight (4%) over the first 5 days of colonization with parallel changes in multiple pathways in all compartments analyzed. The colonization process stimulated glycogenesis in the liver prior to triggering increases in hepatic triglyceride synthesis. These changes were associated with modifications of hepatic Cyp8b1 expression and the subsequent alteration of bile acid metabolites, including taurocholate and tauromuricholate, which are essential regulators of lipid absorption. Expression and activity of major drug-metabolizing enzymes (Cyp3a11 and Cyp2c29) were also significantly stimulated. Remarkably, statistical modeling of the interactions between hepatic metabolic profiles and microbial composition analyzed by 16S rRNA gene pyrosequencing revealed strong associations of the Coriobacteriaceae family with both the hepatic triglyceride, glucose, and glycogen levels and the metabolism of xenobiotics. These data demonstrate the importance of microbial activity in metabolic phenotype development, indicating that microbiota manipulation is a useful tool for beneficially modulating xenobiotic metabolism and pharmacokinetics in personalized health care. PMID:21363910

[Clinical efficacy of alternating chemo-radiotherapy for locally advanced nasopharyngeal carcinoma].

PubMed

You, Xi; Yang, Yucheng

2014-03-01

The purpose of this study is to investigate the effective of alternating Chemo-radiotherapy for locally Advanced Nasopharyngeal Carcinoma. Retrospective analysis 106 cases of patients with locally advanced nasopharyngeal carcinoma between November 2005 and March 2007. All patients received cisplatin-based chemotherapy but 15 patients received radiotherapy(RT) alone. Inducing chemotherapy (IC) + RT + adju-vant chemotherapy (AC) regimen in 36 patients, IC+RT regimen was delivered in 25 patients and AC + RT regimen in 30 patients. 61 patients received 1 to 2 cycles of inducing chemotherapy and 66 patients received 3 to 6 cycles of adjuvant chemotherapy after radiotherapy. Chemotherapy started on the first day after the end of the induction chemotherapy, adjuvant chemotherapy begun after radiotherapy for a week. All patients were treated by radiotherapy using 60 Co r-ray, the nasophyarynx primary site was given a total does of 68 -74 Gy. The lymph nodes of the neck was given 60 to 70 Gy. The prophylactic irradiation does of the neck was 48-50 Gy. RESCULT: The median follow up time was 51 months. A total of 58 patients died, the overall survival rate was 45% in whole groups. The 5-year overall survival rates were 33%, 63%, 60% and 50% in RT, IC + RT + AC, IC + RT and RT+AC group, respectively. The 5-year disease-free survival rates were 13%, 56%, 48% and 40% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year relapse-free survival rates were 13%, 53%, 48% and 50% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year metastasis-free survival rates were 6%, 50%, 44% and 47% in RT, IC + RT + AC, IC+ RT and RT + AC group, respectively. There was significant difference in all groups (P < 0.05). The median time to relapses were 22 months, 29 months, 28 months and 25 months in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The median time to first distant metastasis were 10 months, 19 months, 15 months and 12 months in RT, IC

Butyrate-induced apoptotic cascade in colonic carcinoma cells: modulation of the beta-catenin-Tcf pathway and concordance with effects of sulindac and trichostatin A but not curcumin.

PubMed

Bordonaro, M; Mariadason, J M; Aslam, F; Heerdt, B G; Augenlicht, L H

1999-10-01

Short-chain fatty acids play a critical role in colonic homeostasis because they stimulate pathways of growth arrest, differentiation, and apoptosis. These effects have been well characterized in colonic cell lines in vitro. We investigated the role of beta-catenin-Tcf signaling in these responses to butyrate and other well-characterized inducers of apoptosis of colonic epithelial cells. Unlike wild-type APC, which down-regulates Tcf activity, butyrate, as well as sulindac and trichostatin A, all inducers of G0-G1 cell cycle arrest and apoptosis in the SW620 colonic carcinoma cell line, up-regulate Tcf activity. In contrast, structural analogues of butyrate that do not induce cell cycle arrest or apoptosis and curcumin, which stimulates G2-M arrest without inducing apoptosis, do not alter Tcf activity. Similar to the cell cycle arrest and apoptotic cascade induced by butyrate, the up-regulation of Tcf activity is dependent upon the presence of a mitochondrial membrane potential, unlike the APC-induced down-regulation, which is insensitive to collapse of the mitochondrial membrane potential. Moreover, the butyrate-induced increase in Tcf activity, which is reflected in an increase in beta-catenin-Tcf complex formation, is independent of the down-regulation caused by expression of wild-type APC. Thus, butyrate and wild-type APC have different and independent effects on beta-catenin-Tcf signaling. These data are consistent with other reports that suggest that the absence of wild-type APC, associated with the up-regulation of this signaling pathway, is linked to the probability of a colonic epithelial cell entering an apoptotic cascade.

Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells

PubMed Central

Iessi, Elisabetta; Zischler, Luciana; Etringer, Aurélie; Bergeret, Marion; Morlé, Aymeric; Jacquemin, Guillaume; Morizot, Alexandre; Shirley, Sarah; Lalaoui, Najoua; Elifio-Esposito, Selene L.; Fais, Stefano; Garrido, Carmen; Solary, Eric; Micheau, Olivier

2015-01-01

Ezrin belongs to the ERM (ezrin-radixin-moesin) protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type dependant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton- and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines as well as WWOX silencing or modulation of PKA activation by pharmacological regulators, in the colon cancer cell line SW480, abrogated regulation of TRAIL signalling by ezrin. Altogether our results show that death receptor pro-apoptotic signalling regulation by ezrin can occur downstream of the DISC in colon cancer cells. PMID:26010871

3-Bromopyruvate enhances TRAIL-induced apoptosis in human nasopharyngeal carcinoma cells through CHOP-dependent upregulation of TRAIL-R2.

PubMed

Can, Zhou; Lele, Song; Zhirui, Zhang; Qiong, Pan; Yuzhong, Chen; Lingling, Liu; Surong, Zhao; Yiming, Sun; Pei, Zhang; Chenchen, Jiang; Liu, Hao

2017-08-01

Past reports have shown that the sensitivity of cancer cells to TRAIL-induced apoptosis is related to their expression of TRAIL-death receptors on the cell surface. However, the level of TRAIL-death receptors expression on cancer cells is always low. Our previous research showed that nasopharyngeal carcinoma (NPC) cells have a poor sensitivity to low doses of TRAIL. Here, we evaluated combined treatment with the energy inhibitor 3-bromopyruvate (3BP) and TRAIL as a method to produce an increased apoptotic response in NPC cells. The results showed that 3BP and TRAIL together produced higher cytotoxicity and increased TRAIL-R2 expression in NPC cells compared with the effects of either 3BP or TRAIL alone. These findings led us to hypothesize that 3BP may sensitize NPC cells to TRAIL. 3BP is a metabolic blocker that inhibits hexokinase II activity, suppresses ATP production, and induces endoplasmic reticulum (ER) stress. Our results showed that 3BP also activated AMP-activated protein kinase, which we found to play an important role in the induction of ER stress by 3BP. Furthermore, the induction of TRAIL-R2 expression and the sensitization of the NPC cells to TRAIL by 3BP were reduced when we inhibited the expression of CHOP. Taken together, our results showed that a low dose of 3BP sensitized NPC cells to TRAIL-induced apoptosis by the upregulation of CHOP, which was mediated by the activation of AMP-activated protein kinase and ER stress. The results showed that 3BP is a promising candidate agent for enhancing the therapeutic response to TRAIL in NPC.

Salivary gland and nasopharyngeal cancers in individuals with acquired immunodeficiency syndrome in United States.

PubMed

Shebl, Fatma M; Bhatia, Kishor; Engels, Eric A

2010-05-15

Individuals with acquired immunodeficiency syndrome (AIDS) manifest an increased risk of cancer, particularly cancers caused by oncogenic viruses. Because some salivary gland and nasopharyngeal cancers are associated with Epstein Barr virus, the impact of AIDS on these cancers needs further evaluation. We used linked U.S. AIDS and cancer registry data (N = 519,934 people with AIDS) to derive standardized incidence ratios (SIRs) comparing risk of salivary gland and nasopharyngeal cancers to the general population. For salivary gland cancers (N = 43 cases), individuals with AIDS had strongly elevated risks for lymphoepithelial carcinoma (SIR 39, 95% CI 16-81) and squamous cell carcinoma (SIR 4.9, 95% CI 2.5-8.6). Among nasopharyngeal cancers (N = 39 cases), risks were elevated for both keratinizing and nonkeratinizing carcinomas (SIR 2.4, 95% CI 1.5-3.7 and SIR 2.4, 95% CI 1.2-4.4, respectively). The elevated risks of salivary gland and nasopharyngeal cancers among people with AIDS suggest that immunosuppression and oncogenic viral infections are etiologically important.

Salivary Gland and Nasopharyngeal Cancers in Individuals with Acquired Immunodeficiency Syndrome in United States

PubMed Central

Shebl, Fatma M.; Bhatia, Kishor; Engels, Eric A.

2009-01-01

Individuals with acquired immunodeficiency syndrome (AIDS) manifest an increased risk of cancer, particularly cancers caused by oncogenic viruses. Because some salivary gland and nasopharyngeal cancers are associated with Epstein Barr virus, the impact of AIDS on these cancers needs further evaluation. We used linked U.S. AIDS and cancer registry data (N=519,934 people with AIDS) to derive standardized incidence ratios (SIRs) comparing risk of salivary gland and nasopharyngeal cancers to the general population. For salivary gland cancers (N=43 cases), individuals with AIDS had strongly elevated risks for lymphoepithelial carcinoma (SIR 39, 95% CI 16-81) and squamous cell carcinoma (SIR 4.9, 95% CI 2.5-8.6). Among nasopharyngeal cancers (N=39 cases), risks were elevated for both keratinizing and non-keratinizing carcinomas (SIR 2.4, 95% CI 1.5-3.7, and SIR 2.4, 95% CI 1.2-4.4, respectively). The elevated risks of salivary gland and nasopharyngeal cancers among people with AIDS suggest that immunosuppression and oncogenic viral infections are etiologically important. PMID:19810095

Postirradiation malignant fibrous histiocytoma arising in juvenile nasopharyngeal angiofibroma and producing alpha-1-antitrypsin.

PubMed

Spagnolo, D V; Papadimitriou, J M; Archer, M

1984-03-01

A fatal nasopharyngeal malignant fibrous histiocytoma developed in a young male after irradiation of juvenile nasopharyngeal angiofibroma diagnosed 5 years earlier. The sarcoma extended from the nasopharynx into the floor of the pituitary fossa and into both parasellar regions. There was no clinical evidence of any distant spread. Many of the malignant cells contained cytoplasmic granular and globular PAS-positive inclusions shown to be alpha-1-antitrypsin immunohistochemically. Ultrastructurally, this probably corresponded to electron-dense material with distinctive patterns and which had accumulated within distended ergastoplasmic cisternae of the neoplastic cells. Three previously reported case of postirradiation sarcomas arising in nasopharyngeal angiofibroma were said to be fibrosarcomas and none produced alpha-1-antitrypsin.

SpxB is a suicide gene of Streptococcus pneumoniae and confers a selective advantage in an in vivo competitive colonization model.

PubMed

Regev-Yochay, Gili; Trzcinski, Krzysztof; Thompson, Claudette M; Lipsitch, Marc; Malley, Richard

2007-09-01

The human bacterial pathogen Streptococcus pneumoniae dies spontaneously upon reaching stationary phase. The extent of S. pneumoniae death at stationary phase is unusual in bacteria and has been conventionally attributed to autolysis by the LytA amidase. In this study, we show that spontaneous pneumococcal death is due to hydrogen peroxide (H(2)O(2)), not LytA, and that the gene responsible for H(2)O(2) production (spxB) also confers a survival advantage in colonization. Survival of S. pneumoniae in stationary phase was significantly prolonged by eliminating H(2)O(2) in any of three ways: chemically by supplementing the media with catalase, metabolically by growing the bacteria under anaerobic conditions, or genetically by constructing DeltaspxB mutants that do not produce H(2)O(2). Likewise, addition of H(2)O(2) to exponentially growing S. pneumoniae resulted in a death rate similar to that of cells in stationary phase. While DeltalytA mutants did not lyse at stationary phase, they died at a rate similar to that of the wild-type strain. Furthermore, we show that the death process induced by H(2)O(2) has features of apoptosis, as evidenced by increased annexin V staining, decreased DNA content, and appearance as assessed by transmission electron microscopy. Finally, in an in vivo rat model of competitive colonization, the presence of spxB conferred a selective advantage over the DeltaspxB mutant, suggesting an explanation for the persistence of this gene. We conclude that a suicide gene of pneumococcus is spxB, which induces an apoptosis-like death in pneumococci and confers a selective advantage in nasopharyngeal cocolonization.

SpxB Is a Suicide Gene of Streptococcus pneumoniae and Confers a Selective Advantage in an In Vivo Competitive Colonization Model▿

PubMed Central

Regev-Yochay, Gili; Trzcinski, Krzysztof; Thompson, Claudette M.; Lipsitch, Marc; Malley, Richard

2007-01-01

The human bacterial pathogen Streptococcus pneumoniae dies spontaneously upon reaching stationary phase. The extent of S. pneumoniae death at stationary phase is unusual in bacteria and has been conventionally attributed to autolysis by the LytA amidase. In this study, we show that spontaneous pneumococcal death is due to hydrogen peroxide (H2O2), not LytA, and that the gene responsible for H2O2 production (spxB) also confers a survival advantage in colonization. Survival of S. pneumoniae in stationary phase was significantly prolonged by eliminating H2O2 in any of three ways: chemically by supplementing the media with catalase, metabolically by growing the bacteria under anaerobic conditions, or genetically by constructing ΔspxB mutants that do not produce H2O2. Likewise, addition of H2O2 to exponentially growing S. pneumoniae resulted in a death rate similar to that of cells in stationary phase. While ΔlytA mutants did not lyse at stationary phase, they died at a rate similar to that of the wild-type strain. Furthermore, we show that the death process induced by H2O2 has features of apoptosis, as evidenced by increased annexin V staining, decreased DNA content, and appearance as assessed by transmission electron microscopy. Finally, in an in vivo rat model of competitive colonization, the presence of spxB conferred a selective advantage over the ΔspxB mutant, suggesting an explanation for the persistence of this gene. We conclude that a suicide gene of pneumococcus is spxB, which induces an apoptosis-like death in pneumococci and confers a selective advantage in nasopharyngeal cocolonization. PMID:17631628

Rare metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes: A case report and literature review.

PubMed

Cai, Changjing; Shen, Hong; Liu, Wenqiang; Ma, Junli; Zhang, Yan; Yin, Ling; Li, Jindong; Shen, Liangfang; Zeng, Shan

2017-11-01

Thyroid metastasis from nasopharyngeal carcinoma is rare. Metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes hasn't been reported before. We want to share our experience about the treatment choice. A 27-year-old man was diagnosed with nasopharyngeal nonkeratinizing carcinoma in August 2004. In March 2013 he underwent a thyroid carcinoma radical operation, and histological examination revealed metastasis to the thyroid gland from nasopharyngeal carcinoma. An 18F-FDG-PET/CT scan and biopsy showed metastatic abdominal lymph nodes of nasopharyngeal carcinoma in April 2015. A 27-year-old man was diagnosed with metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes. The patient was treated with concurrent chemotherapy and radiotherapy for nasopharyngeal carcinoma and metastasis to the thyroid gland. The metastases to the abdominal lymph nodes received chemotherapy. After 6 cycles of chemotherapy with gemcitabine, cisplatin, and 5-fluorouracil for metastasis to the abdominal lymph nodes, the patient is currently asymptomatic with stable disease and improved quality of life. The treatment choice for metastasis of nasopharyngeal carcinoma depends on the clinical disease extent, and surgery and/or chemo-radiation therapy must be drafted to the individual patient in order to improve the prognosis and quality of life.

Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis.

PubMed

Nam, Joon; Kim, Wooseong; Lee, Sunyoung; Jeong, Seongkeun; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

2016-01-01

Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine.

Regulatory effect of the AMPK-COX-2 signaling pathway in curcumin-induced apoptosis in HT-29 colon cancer cells.

PubMed

Lee, Yun-Kyoung; Park, Song Yi; Kim, Young-Min; Park, Ock Jin

2009-08-01

AMP-activated protein kinase (AMPK), a highly conserved protein in eukaryotes, functions as a major metabolic switch to maintain energy homeostasis. It also intrinsically regulates the mammalian cell cycle. Moreover, the AMPK cascade has emerged as an important pathway implicated in cancer control. In this study we investigated the effects of curcumin on apoptosis and the regulatory effect of the AMPK-cyclooxygenase-2 (COX-2) pathway in curcumin-induced apoptosis. Curcumin has shown promise as a chemopreventive agent because of its in vivo regression of various animal-model colon cancers. This study focused on exploiting curcumin to apply antitumorigenic effects through modulation of the AMPK-COX-2 cascade. Curcumin exhibited a potent apoptotic effect on HT-29 colon cancer cells at concentrations of 50 micromol/L and above. These apoptotic effects were correlated with the decrease in pAkt and COX-2, as well as the increase in p-AMPK. Cell cycle analysis showed that curcumin induced G(1)-phase arrest. Further study with AMPK synthetic inhibitor Compound C has shown that increased concentrations of Compound C would abolish AMPK expression, accompanied by a marked increase in COX-2 as well as pAkt expression in curcumin-treated HT-29 cells. By inhibiting AMPK with Compound C, we found that curcumin-treated colon cancer cells were no longer undergoing apoptosis; rather, they were proliferative. These results indicate that AMPK is crucial in apoptosis induced by curcumin and further that the pAkt-AMPK-COX-2 cascade or AMPK-pAkt-COX-2 pathway is important in cell proliferation and apoptosis in colon cancer cells.

The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway.

PubMed

Larrosa, Mar; Tomás-Barberán, Francisco A; Espín, Juan Carlos

2006-09-01

Polyphenol-rich dietary foodstuffs have attracted attention due to their cancer chemopreventive and chemotherapeutic properties. Ellagitannins (ETs) belong to the so-called hydrolysable tannins found in strawberries, raspberries, walnuts, pomegranate, oak-aged red wine, etc. Both ETs and their hydrolysis product, ellagic acid (EA), have been reported to induce apoptosis in tumour cells. Ellagitannins are not absorbed in vivo but reach the colon and release EA that is metabolised by the human microflora. Our aim was to investigate the effect of a dietary ET [pomegranate punicalagin (PUNI)] and EA on human colon cancer Caco-2 and colon normal CCD-112CoN cells. Both PUNI and EA provoked the same effects on Caco-2 cells: down-regulation of cyclins A and B1 and upregulation of cyclin E, cell-cycle arrest in S phase, induction of apoptosis via intrinsic pathway (FAS-independent, caspase 8-independent) through bcl-XL down-regulation with mitochondrial release of cytochrome c into the cytosol, activation of initiator caspase 9 and effector caspase 3. Neither EA nor PUNI induced apoptosis in normal colon CCD-112CoN cells (no chromatin condensation and no activation of caspases 3 and 9 were detected). In the case of Caco-2 cells, no specific effect can be attributed to PUNI since it was hydrolysed in the medium to yield EA, which entered into the cells and was metabolised to produce dimethyl-EA derivatives. Our study suggests that the anticarcinogenic effect of dietary ETs could be mainly due to their hydrolysis product, EA, which induced apoptosis via mitochondrial pathway in colon cancer Caco-2 cells but not in normal colon cells.

Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression.

PubMed

Zakraoui, Ons; Marcinkiewicz, Cezary; Aloui, Zohra; Othman, Houcemeddine; Grépin, Renaud; Haoues, Meriam; Essafi, Makram; Srairi-Abid, Najet; Gasmi, Ammar; Karoui, Habib; Pagès, Gilles; Essafi-Benkhadir, Khadija

2017-01-01

Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53-dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of α5β1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma.

PubMed

Hu, Qian; Lin, Xiao; Ding, Linxiaoxiao; Zeng, Yinduo; Pang, Danmei; Ouyang, Nengtai; Xiang, Yanqun; Yao, Herui

2018-06-24

Rho GTPase-activating protein 42 was identified as an inhibitor of RhoA to maintain normal blood pressure homeostasis. However, the effect of ARHGAP42 in promoting cell malignancy in nasopharyngeal carcinoma is demonstrated in this study. Microarray and real-time quantitative PCR were used for a mRNA profiling of ARHGAP42 in nasopharyngeal primary and metastatic carcinoma tissues. Western blot and immunohistochemical staining were used for detecting the expression of ARHGAP42 protein in nasopharyngeal carcinoma tissues and cell lines. The overexpression and silence experiments of ARHGAP42 were performed in NPC cell lines using siRNA and expressive plasmid for evaluating cancer cell migration and invasion in vitro. Real-time quantitative PCR, western blot, and transwell test were employed for with the function of ARHGAP42 and its antisense lncRNA uc010rul. We confirmed the elevated expression of ARHGAP42 in metastatic NPC tissues of mRNA and protein for the first time. Immunohistochemical analysis indicated that NPC patients with highly ARHGAP42 expression were significantly associated with shorter metastasis-free survival. Knockdown of ARHGAP42 resulted in significant inhibition of nasopharyngeal cancer cell migration and invasion in vitro, and the overexpression of ARHGAP42 showed the opposite effects. In addition, the silence of uc010rul resulted in ARHGAP42 expression decrease and significant inhibition of nasopharyngeal cancer cell migration and invasion. High expression of ARHGAP42 is associated with poor metastasis-free survival of nasopharyngeal carcinoma patients. ARHGAP42 promotes migration and invasion of nasopharyngeal carcinoma cells in vitro; the antisense lncRNA may be involved in this effect. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Intracolonic capsaicin stimulates colonic motility and defecation in conscious dogs.

PubMed

Hayashi, Keiichi; Shibata, Chikashi; Nagao, Munenori; Sato, Manabu; Kakyo, Masayuki; Kinouchi, Makoto; Saijo, Fumito; Miura, Koh; Ogawa, Hitoshi; Sasaki, Iwao

2010-06-01

The aim of this study was to investigate the effects of intracolonic capsaicin on colonic motility and defecation. The effects of capsaicin (1, 2, 5, and 10 mg) administrated into the proximal colon on ileocolonic motility and defecation were studied in neurally intact dogs with or without various antagonists (atropine, hexamethonium, ondansetron, propranolol, and FK224), dogs with extrinsic denervation of an ileocolonic segment, and dogs with enterically isolated ileocolonic loops equipped with strain gauge force transducers. Capsaicin at 5 and 10 mg evoked giant migrating contractions in a dose-independent manner, and it induced defecations with more than 90% probability in neurally intact dogs. These effects of capsaicin were abolished by atropine and hexamethonium. Ondansetron inhibited the capsaicin-induced increase in colonic motility but did not affect the induction of defecation. The other antagonists had no effect. In dogs with extrinsic denervation, capsaicin did not evoke giant migrating contractions in the colon but still induced defecation in 30-40% of experiments. In dogs with ileocolonic loops, capsaicin did not stimulate colonic motility nor induce defecation. These results indicate that intracolonic capsaicin causes giant migrating contractions and defecation. Intact extrinsic innervation, continuity of the colon, and intraluminal contents were considered necessary for this effect. Copyright 2010 Mosby, Inc. All rights reserved.

Selenium Nanoparticles Induce the Chemo-Sensitivity of Fluorouracil Nanoparticles in Breast and Colon Cancer Cells.

PubMed

Abd-Rabou, Ahmed A; Shalby, Aziza B; Ahmed, Hanaa H

2018-05-11

Drug resistance is a major challenge of breast and colon cancer therapies leading to treatment failure. The main objective of the current study is to investigate whether selenium nanoparticles (nano-Se) can induce the chemo-sensitivity of 5-fluorouracil (FU)-encapsulated poly (D, L-lactide-co-glycolide) nanoparticles (nano-FU) in breast and colon cancer cell lines. Nano-Se and nano-FU were synthesized and characterized, then applied individually or in combination upon MCF7, MDA-MB-231, HCT 116, and Caco-2 cancerous cell lines. Cytotoxicity, cellular glucose uptake, and apoptosis, as well as malondialdehyde (MDA), nitric oxide (NO), and zinc (Zn) levels, were investigated upon the different treatments. We have resulted that nano-FU induced cell death in MCF7 and Caco-2 more effectively than MDA-MB-231 and HCT 116 cell lines. Moreover, nano-FU plus nano-Se potentiate MCF7 and Caco-2 chemo-sensitivity were higher than MDA-MB-231 and HCT 116 cancerous cell lines. It is relevant to note that Se and FU nano-formulations inhibited cancer cell bioenergetics via glucose uptake slight blockage. Furthermore, nano-FU increased the levels of NO and MDA in media over cancer cells, while their combinations with nano-Se rebalance the redox status with Zn increment. We noticed that MCF7 cell line is sensitive, while MDA-MB-231 cell line is resistant to Se and nano-Se. This novel approach could be of great potential to enhance the chemo-sensitivity in breast and colon cancer cells.

Does rapid maxillary expansion increase nasopharyngeal space and improve nasal airway resistance?

PubMed

Langer, Marjorie Regina Eguren; Itikawa, Carla Enoki; Valera, Fabiana Cardoso Pereira; Matsumoto, Mírian Aiko Nakane; Anselmo-Lima, Wilma Terezinha

2011-01-01

To evaluate the effect of rapid maxillary expansion (RME) on the dimension of the nasopharyngeal space and its relation to nasal airway resistance. Twenty-five school-age children (from 7 to 10 year-old) with mouth and/or mixed breathing, with mixed dentition and uni- or bilateral posterior crossbite involving the deciduous canines and the first permanent molars, were evaluated. RME was placed and remained during 90 days. Rhinomanometry and orthodontic documentation were performed at four different times, i.e., before (T(1)), immediately after (T(2)), 90 days (T(3)) and 30 months (T(4)) after RME. Differences in nasopharyngeal area and in nasal airway resistance were observed only 30 months after RME, and could be explained by facial growth, and not because of the orthodontic procedure. RME does not influence on nasopharyngeal area or nasal airway resistance in long-term evaluation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of dietary fiber on the activity of intestinal and fecal beta-glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis.

PubMed

Manoj, G; Thampi, B S; Leelamma, S; Menon, P V

2001-01-01

The effects of fiber isolated from black gram (Phaseolus mungo) and coconut (Cocos nucifera) kernel on the metabolic activity of intestinal and fecal beta glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis were studied. The results indicated that the inclusion of fiber from black gram and coconut kernel generally supported lower specific activities and less fecal output of beta-glucuronidase than did the fiber free diet. This study suggests that the fibers isolated from coconut or black gram may potentially play a role in preventing the formation of colon tumors induced by the carcinogen 1,2-dimethylhydrazine by reducing the activity of the intestinal as well as fecal beta-glucuronidase.

High sensitivity of gold nanoparticles co-doped with Gd2O3 mesoporous silica nanocomposite to nasopharyngeal carcinoma cells

NASA Astrophysics Data System (ADS)

Wang, Hui; Zhang, Songjin; Tian, Xiumei; Liu, Chufeng; Zhang, Lei; Hu, Wenyong; Shao, Yuanzhi; Li, Li

2016-10-01

Nanoprobes for combined optical and magnetic resonance imaging have tremendous potential in early cancer diagnosis. Gold nanoparticles (AuNPs) co-doped with Gd2O3 mesoporous silica nanocomposite (Au/Gd@MCM-41) can produce pronounced contrast enhancement for T1 weighted image in magnetic resonance imaging (MRI). Here, we show the remarkably high sensitivity of Au/Gd@MCM-41 to the human poorly differentiated nasopharyngeal carcinoma (NPC) cell line (CNE-2) using fluorescence lifetime imaging (FLIM). The upconversion luminescences from CNE-2 and the normal nasopharyngeal (NP) cells (NP69) after uptake of Au/Gd@MCM-41 show the characteristic of two-photon-induced-radiative recombination of the AuNPs. The presence of the Gd3+ ion induces a much shorter luminescence lifetime in CNE-2 cells. The interaction between AuNPs and Gd3+ ion clearly enhances the optical sensitivity of Au/Gd@MCM-41 to CNE-2. Furthermore, the difference in the autofluorescence between CNE-2 and NP69 cells can be efficiently demonstrated by the emission lifetimes of Au/Gd@MCM-41 through the Forster energy transfers from the endogenous fluorophores to AuNPs. The results suggest that Au/Gd@MCM-41 may impart high optical resolution for the FLIM imaging that differentiates normal and high-grade precancers.

A longitudinal study on the radiation-induced thyroid gland changes after external beam radiotherapy of nasopharyngeal carcinoma.

PubMed

Lin, Zhixiong; Wu, Vincent Wing-Cheung; Lin, Jing; Feng, Huiting; Chen, Longhua

2011-01-01

Radiation-induced thyroid disorders have been reported in radiotherapy of head and neck cancers. This study evaluated the radiation-induced damages to thyroid gland in patients with nasopharyngeal carcinoma (NPC). Forty-five patients with NPC treated by radiotherapy underwent baseline thyroid hormones (free triiodothyronine, free thyroxine [fT4], and thyrotropin [TSH]) examination and CT scan before radiotherapy. The volume of the thyroid gland was calculated by delineating the structure in the corresponding CT slices using the radiotherapy treatment planning system. The thyroid doses were estimated using the treatment planning system. Subsequent CT scans were conducted at 6, 12, and 18 months after radiotherapy, whereas the hormone levels were assessed at 3, 6, 12, and 18 months after radiotherapy. Trend lines of the volume and hormone level changes against time were plotted. The relationship between the dose and the change of thyroid volume and hormone levels were evaluated using the Pearson correlation test. An average of 20% thyroid volume reduction in the first 6 months and a further 8% shrinkage at 12 months after radiotherapy were observed. The volume reduction was dependent on the mean thyroid doses at 6, 12, and 18 months after radiotherapy (r = -0.399, -0.472, and -0.417, respectively). Serum free triiodothyronine and fT4 levels showed mild changes of <2.5% at 6 months, started to drop by 8.8% and 11.3%, respectively, at 12 months, and became stable at 18 months. The mean serum TSH level increased mildly at 6 months after radiotherapy and more steeply after 18 months. At 18 months after radiotherapy, 12 patients had primary hypothyroidism with an elevated serum TSH, in which 4 of them also presented with low serum fT4. There was a significant difference (p = 0.014) in the mean thyroid doses between patients with hypothyroidism and normal thyroid function. Radiotherapy for patients with NPC caused radiation-induced changes of the thyroid gland. The

[Long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma].

PubMed

Zhang, Xiangmin; Yu, Lijiang; Wu, Wei; Wu, Xiuhong; Xiao, Fufu; Zeng, Guoxing; Lan, Xiaolin

2013-02-01

To evaluate the long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma. Sixty-five cases of nasopharyngeal carcinoma patients were randomly divided into study group of 32 patients and control group of 33 patents. The submandibular gland was transferred to submental region on 32 cases with nasopharyngeal carcinoma before receiving conventional radiotherapy and a block was used to cover the submental region. Before radiotherapy, two groups of submandibular gland function was detected by imaging of the submandibular gland. At 60 months after radiotherapy, submandibular gland function was detected by 99mTc radionuclide scanning, the questionnaire about the degree of xerostomia was investigated respectively. Five-year survival rate was counted. After following up for 60 months, submandibular gland uptake and secretion function in the study group was significantly higher than that in the control group, there was significant difference between the two groups (P < 0.01) respectively. The incidence of moderate or severe xerostomia in the study group was significantly lower than that in the control group (15.4% vs 76.9%, P < 0.01). Five-year survival rate of the study group and control group was 81.3% and 78.8% respectively, there was no significant difference between the two groups (P > 0.05). The long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma was well. It could improve the quality of life in nasopharyngeal carcinoma patients after radiotherapy, and did not affect the long-term efficacy of nasopharyngeal carcinoma.

Choline acetyltransferase and organic cation transporters are responsible for synthesis and propionate-induced release of acetylcholine in colon epithelium.

PubMed

Bader, Sandra; Klein, Jochen; Diener, Martin

2014-06-15

Acetylcholine is not only a neurotransmitter, but is found in a variety of non-neuronal cells. For example, the enzyme choline acetyltransferase (ChAT), catalyzing acetylcholine synthesis, is expressed by the colonic epithelium of different species. These cells release acetylcholine across the basolateral membrane after luminal exposure to propionate, a short-chain fatty acid. The functional consequence is the induction of chloride secretion, measurable as increase in short-circuit current (Isc) in Ussing chamber experiments. It is unclear how acetylcholine is produced and released by colonic epithelium. Therefore, the aim of the present study was the identification (on mRNA and protein level) and functional characterization (in Ussing chamber experiments combined with HPLC detection of acetylcholine) of transporters/enzymes in the cholinergic system of rat colonic epithelium. Immunohistochemical staining as well as RT-PCR revealed the expression of high-affinity choline transporter, ChAT, carnitine acetyltransferase (CarAT), vesicular acetylcholine transporter (VAChT), and organic cation transporters (OCT 1, 2, 3) in colonic epithelium. In contrast to blockade of ChAT with bromoacetylcholine, inhibition of CarAT with mildronate did not inhibit the propionate-induced increase in Isc, suggesting a predominant synthesis of epithelial acetylcholine by ChAT. Although being expressed, blockade of VAChT with vesamicol was ineffective, whereas inhibition of OCTs with omeprazole and corticosterone inhibited propionate-induced Isc and the release of acetylcholine into the basolateral compartment. In summary, OCTs seem to be involved in regulated acetylcholine release by colonic epithelium, which is assumed to be involved in chemosensing of luminal short-chain fatty acids by the intestinal epithelium. Copyright © 2014 Elsevier B.V. All rights reserved.

Acetaminophen and Metamizole Induce Apoptosis in HT 29 and SW 480 Colon Carcinoma Cell Lines In Vitro.

PubMed

Bundscherer, Anika C; Malsy, Manuela; Gruber, Michael A; Graf, Bernhard M; Sinner, Barbara

2018-02-01

The perioperative phase is supposed to be a period with high vulnerability for cancer dissemination. Acetaminophen and metamizole are common analgesics administered during this phase. We investigated the effect of acetaminophen, metamizole and 4-methylaminoantipyrine (MAA) on proliferation and apoptosis of colon carcinoma cell lines (SW 480 and HT 29). Proliferation was detected by cell proliferation ELISA BrdU, and apoptosis by Annexin V staining. Cytochrome c and caspase 3, 8 and 9 expression levels were detected by western blot. Acetaminophen, metamizole or MAA caused slight changes in proliferation. Acetaminophen, metamizole or the combination increased apoptosis in both cell lines. All agents decreased caspase 3 and 8 expression in SW480. Acetaminophen decreased caspase 9 expression in both cell lines. In clinically relevant doses, acetaminophen and/or metamizole induce apoptosis in both colon cancer cell lines. Both mitochondrial and death receptor pathways might be involved in acetaminophen-induced apoptosis. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Astaxanthin inhibits tumor invasion by decreasing extracellular matrix production and induces apoptosis in experimental rat colon carcinogenesis by modulating the expressions of ERK-2, NFkB and COX-2.

PubMed

Nagendraprabhu, Ponnuraj; Sudhandiran, Ganapasam

2011-04-01

Colon cancer is the third most malignant neoplasm in the world and it remains an important cause of mortality in Asian and Western countries. Astaxanthin (AST), a major component of carotenoids possesses attractive remedial features. The purpose of this study is to investigate the possible mechanism of action of astaxanthin against 1, 2 dimethyl hydrazine (DMH)-induced rat colon carcinogenesis. Wistar male rats were randomized into five groups, group 1 were control rats, group 2 were rats that received AST (15 mg/kg body wt p.o. everyday), rats in group 3 were induced with DMH (40 mg/kg body wt, s.c.), DMH-induced rats in groups 4 and 5 were either pre or post initiated with AST, respectively as in group 2. DMH-induced rats exhibited elevated expressions of Nuclear factor kappa B-p65 (NF-κB-p65), Cyclooxygenase-2 (COX-2), Matrixmetallo proteinases (MMP) 2/9, Proliferating cell nuclear antigen (PCNA), and Extracellular signal-regulated kinase-2 (ERK-2) as confirmed by immunofluorescence. Further, Westernblot analysis of MMPs-2/9, ERK-2 and Protein kinase B (Akt) revealed increased expressions of these proteins in DMH-induced groups of rats. AST-treatment decreased the expressions of all these vital proteins, involved in colon carcinogenesis. The ability of AST to induce apoptosis in the colon of DMH-induced rats was confirmed by Annexin-V/PI staining in a confocal microscopy, DNA fragmentation analysis and expression of caspase-3 by Western blotting. In conclusion, astaxanthin exhibits anti-inflammatory and anti-cancer effects by inducing apoptosis in DMH-induced rat colon carcinogenesis by modulating the expressions of NFkB, COX-2, MMPs-2/9, Akt and ERK-2.

8-C-(E-phenylethenyl)quercetin from onion/beef soup induces autophagic cell death in colon cancer cells through ERK activation.

PubMed

Zhao, Yueliang; Fan, Daming; Zheng, Zong-Ping; Li, Edmund T S; Chen, Feng; Cheng, Ka-Wing; Wang, Mingfu

2017-02-01

Quercetin, a flavonoid, widely distributed in edible fruits and vegetables, was reported to effectively inhibit 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) formation in a food model (roast beef patties) with itself being converted into a novel compound 8-C-(E-phenylethenyl)quercetin (8-CEPQ). Here we investigated whether 8-CEPQ could be formed in a real food system, and tested its anticancer activity in human colon cancer cell lines. LC-MS was applied for the determination of 8-CEPQ formation in onion/beef soup. Anticancer activity of 8-CEPQ was evaluated by using cell viability assay and flow cytometry. Results showed that 8-CEPQ suppressed proliferation and caused G 2 phase arrest in colon cancer cells. Based on immunofluorescent staining assay, western blot assay, and RNA knockdown data, we found that 8-CEPQ did not cause apoptotic cell death. Instead, it induced autophagic cell death. Moreover, treatment with 8-CEPQ induced phosphorylation of extracellular signal-regulated kinase (ERK). Inhibition of ERK phosphorylation by the mitogen-activated protein kinase kinase (MEK)/ERK inhibitor U0126 attenuated 8-CEPQ-induced autophagy and reversed 8-CEPQ-mediated cell growth inhibition. Our results demonstrate that 8-CEPQ, a novel quercetin derivative, could be formed in onion/beef soup. 8-CEPQ inhibited colon cancer cell growth by inducing autophagic cell death through ERK activation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibitory effect of peptide Epitalon on colon carcinogenesis induced by 1,2-dimethylhydrazine in rats.

PubMed

Anisimov, Vladimir N; Khavinson, Vladimir Kh; Popovich, I G; Zabezhinski, Mark A

2002-09-08

The effect of synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on colon carcinogenesis was firstly studied in rats. Eighty 2-month-old outbred male LIO rats were subdivided into four groups and were weekly exposed to five subcutaneous injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg body weight. Additionally, 5 days a week, some of the rats were given subcutaneous injections of saline at a dose of 0.1 ml during the whole experiment (group 1, control) or Epitalon at a single dose of 1 microg during the whole experiment (group 2), Epitalon after termination of carcinogen injections (group 3) or during the period of DMH exposure (group 4). Colon carcinomas developed in 90-100% of DMH-treated rats. The number of total colon tumors per rat was 4.1; 2.7; 3.7; 2.9 in groups 1, 2, 3, 4, respectively (the difference in groups 2 and 4 compared with group 1 is significant). In rats from group 2, colon tumors were smaller than in control animals. In group 2, the incidence, as well the multiplicity of tumors in ascending and descending colon, were significantly decreased in comparison with group 1. In group 4, the mean number of tumors per rat was significantly decreased, too. A trend to decrease the number of tumors in the rectum in rats from groups 2, 3 and 4, treated with Epitalon was found. Epitalon inhibited also the development of tumors in jejunum and ileum. Thus, our results demonstrated an inhibitory effect of Epitalon on chemically induced bowel carcinogenesis in rats.

More Protection of Lactobacillus acidophilus Than Bifidobacterium bifidum Probiotics on Azoxymethane-Induced Mouse Colon Cancer.

PubMed

Agah, Shahram; Alizadeh, Ali Mohammad; Mosavi, Maryam; Ranji, Peyman; Khavari-Daneshvar, Hossein; Ghasemian, Farnaz; Bahmani, Sahar; Tavassoli, Abbas

2018-04-22

Based on the ability of the probiotics in the gut microflora modification, they can have the beneficial effects on diseases in the short and/or the long term. In previous study, we revealed that unlike Bifidobacterium bifidum, the amount of Lactobacillus acidophilus remained almost unchanged in mice gut microflora in the long term, indicating more stability of L. acidophilus than B. bifidum which can be used to prevent some incurable diseases such as cancer. Thirty-eight male BALB/c mice were divided into four groups, control, azoxymethane (AOM), L. acidophilus, and B. bifidum probiotics, to evaluate the protective effects of the probiotics on AOM-induced mouse colon cancer. Except for the control group, the rest of the animals were weekly given AOM (15 mg/kg, s.c) in three consecutive weeks. Colon lesion incidence was 74% in the AOM group in comparison with the control (0%) (P < 0.05). The lesions were varied from mild to severe dysplasia and colonic adenocarcinoma. Administration of the probiotics inhibited the incidence of colonic lesions by about 57% in L. acidophilus (P < 0.05) and 27% in B. bifidum (P > 0.05) compared to the AOM group. The serum levels of CEA and CA19-9 tumor markers were significantly decreased in L. acidophilus in comparison with the AOM group (P < 0.05). Moreover, the serum levels of IFN-γ and IL-10 and the number of CD4 + and CD8 + cells were significantly increased in L. acidophilus compared to AOM (P < 0.05). Our study highlighted the more potential effects of L. acidophilus probiotic than B. bifidum on mouse colon cancer.

Development of a normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism in nasopharyngeal carcinoma patients.

PubMed

Luo, Ren; Wu, Vincent W C; He, Binghui; Gao, Xiaoying; Xu, Zhenxi; Wang, Dandan; Yang, Zhining; Li, Mei; Lin, Zhixiong

2018-05-18

The objectives of this study were to build a normal tissue complication probability (NTCP) model of radiation-induced hypothyroidism (RHT) for nasopharyngeal carcinoma (NPC) patients and to compare it with other four published NTCP models to evaluate its efficacy. Medical notes of 174 NPC patients after radiotherapy were reviewed. Biochemical hypothyroidism was defined as an elevated level of serum thyroid-stimulating hormone (TSH) value with a normal or decreased level of serum free thyroxine (fT4) after radiotherapy. Logistic regression with leave-one-out cross-validation was performed to establish the NTCP model. Model performance was evaluated and compared by the area under the receiver operating characteristic curve (AUC) in our NPC cohort. With a median follow-up of 24 months, 39 (22.4%) patients developed biochemical hypothyroidism. Gender, chemotherapy, the percentage thyroid volume receiving more than 50 Gy (V 50 ), and the maximum dose of the pituitary (P max ) were identified as the most predictive factors for RHT. A NTCP model based on these four parameters were developed. The model comparison was made in our NPC cohort and our NTCP model performed better in RHT prediction than the other four models. This study developed a four-variable NTCP model for biochemical hypothyroidism in NPC patients post-radiotherapy. Our NTCP model for RHT presents a high prediction capability. This is a retrospective study without registration.

Purple rice extract supplemented diet reduces DMH- induced aberrant crypt foci in the rat colon by inhibition of bacterial β-glucuronidase.

PubMed

Summart, Ratasark; Chewonarin, Teera

2014-01-01

Purple rice has become a natural product of interest which is widely used for health promotion. This study investigated the preventive effect of purple rice extract (PRE) mixed diet on DMH initiation of colon carcinogenesis. Rats were fed with PRE mixed diet one week before injection of DMH (40 mg/kg of body weight once a week for 2 weeks). They were killed 12 hrs after a second DMH injection to measure the level of O6-methylguanine and xenobiotic metabolizing enzyme activities. In rats that received PRE, guanine methylation was reduced in the colonic mucosa, but not in the liver, whereas PRE did not affect xenobiotic conjugation, with reference to glutathione-S-transferase or UDP-glucuronyl transferase. After 5 weeks, rats that received PRE with DMH injection had fewer ACF in the colon than those treated with DMH alone. Interestingly, a PRE mixed diet inhibited the activity of bacterial β-glucuronidase in rat feces, a critical enzyme for free methylazoxymethanol (MAM) release in the rat colon. These results indicated that purple rice extract inhibited β-glucuronidase activity in the colonic lumen, causing a reduction of MAM-induced colonic mucosa DNA methylation, leaded to decelerated formation of aberrant crypt foci in the rat colon. The supplemented purple rice extract might thus prevent colon carcinogenesis by the alteration of the colonic environment, and thus could be further developed for neutraceutical products for colon cancer prevention.

α-Hederin inhibits interleukin 6-induced epithelial-to-mesenchymal transition associated with disruption of JAK2/STAT3 signaling in colon cancer cells.

PubMed

Sun, Dongdong; Shen, Weixing; Zhang, Feng; Fan, Huisen; Xu, Changliang; Li, Liu; Tan, Jiani; Miao, Yunjie; Zhang, Haibin; Yang, Ye; Cheng, Haibo

2018-05-01

Colon cancer is the third most frequently diagnosed malignancy and has high morbidity worldwide. Epithelial-mesenchymal transition (EMT) has been increasingly implicated in colon cancer progression and metastasis. The present study was aimed to evaluate the potential antitumor activity of α-hederin, a monodesmosidic triterpenoid saponin isolated from Hedera helix, in human SW620 colon cancer cells stimulated with interleukin 6 (IL-6) for mimicking the tumor inflammatory microenvironment in vivo. Cell viability assay showed that IL-6 at 6.25 ng/ml significantly enhanced viability of SW620 cells, and thus this concentration was used to stimulate SW620 cells throughout this study. We observed that α-hederin concentration-dependently inhibited cell viability, migration and invasion in IL-6-treated SW620 cells. Moreover, α-hederin significantly restored IL-6-induced decrease in E-cadherin expression and abolished IL-6-induced increase in N-cadherin, vimentin, fibronectin, twist and snail at both mRNA and protein levels in SW620 cells. These data suggested that α-hederin suppressed IL-6-indcued EMT in colon cancer cells. Further molecular examinations showed that α-hederin inhibited phosphorylation of Janus Kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3(STAT3), and halted the nuclear translocation of phosphorylated STAT3 in IL-6-treated SW620 cells. In addition, JAK2/STAT3 signaling inhibitor AG490 not only produced similar inhibitory effects on EMT markers as α-hederin, but also synergistically enhanced α-hederin's inhibitory effects on EMT markers in IL-6-treated SW620 cells. Altogether, we demonstrated that α-hederin suppressed IL-6-induced EMT associated with disruption of JAK2/STAT3 signaling in colon cancer cells. Our data strongly suggested α-hederin as a promising candidate for intervention of colon cancer and metastasis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Vanadium inhibits DNA-protein cross-links and ameliorates surface level changes of aberrant crypt foci during 1,2-dimethylhydrazine induced rat colon carcinogenesis.

PubMed

Kanna, P Suresh; Saralaya, M G; Samanta, K; Chatterjee, M

2005-01-01

The trace mineral vanadium inhibits cancer development in a variety of experimental animal models. The present study was to gain insight into a putative anticancer effect of vanadium in a rat model of colon carcinogenesis. The in vivo study was intended to clarify the effect of vanadium on DNA-protein cross-links (DPC), surface level changes of aberrant crypt foci (ACF) and biotransformation status during 1,2-dimethylhydrazine (1,2-DMH) induced preneoplastic rat colon carcinogenesis. The comet assay showed statistically higher mean base values of DNA-protein mass (p<0.01) and mean frequencies of tailed cells (p<0.001) in the carcinogen-induced group after treatment with proteinase K. Treatment with vanadium in the form of ammonium monovanadate supplemented ad libitum in drinking water for the entire experimental period caused a significant (p<0.02) reduction (40%) in DNA-protein cross-links in colon cells. Further, the biotransformation status of vanadium was ascertained measuring the drug metabolising enzymes, glutathione S-transferase (GST) and cytochrome P-450 (Cyt P-450). Significantly, there was an increase in glutathione S-transferase and cytochrome P-450 levels (p<0.01 and p<0.02, respectively) in rats supplemented with vanadium as compared to their carcinogen controls. As an endpoint marker, we also evaluated the effect of vanadium on surface level changes of aberrant crypt foci induced by 1,2-DMH by scanning electron microscopy. Animals induced with 1,2-DMH and supplemented with vanadium showed a marked improvement in colonic architecture with less number of aberrant crypt foci in contrast to the animals induced with 1,2-DMH alone, thereby exhibiting its anti-carcinogenicity by modulating the markers studied herein.

The adult nasopharyngeal microbiome as a determinant of pneumococcal acquisition.

PubMed

Cremers, Amelieke Jh; Zomer, Aldert L; Gritzfeld, Jenna F; Ferwerda, Gerben; van Hijum, Sacha Aft; Ferreira, Daniela M; Shak, Joshua R; Klugman, Keith P; Boekhorst, Jos; Timmerman, Harro M; de Jonge, Marien I; Gordon, Stephen B; Hermans, Peter Wm

2014-01-01

Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volunteers were assessed for pneumococcal carriage by culture of nasal wash samples (NWS). Those without natural pneumococcal carriage received an intranasal pneumococcal inoculation with serotype 6B or 23F. The composition of the nasopharyngeal microbiome was longitudinally studied by 16S rDNA pyrosequencing on NWS collected before and after challenge. Among 40 selected volunteers, 10 were natural carriers and 30 were experimentally challenged. At baseline, five distinct nasopharyngeal microbiome profiles were identified. The phylogenetic distance between microbiomes of natural pneumococcal carriers was particularly large compared to non-carriers. A more diverse microbiome prior to inoculation was associated with the establishment of pneumococcal carriage. Perturbation of microbiome diversity upon pneumococcal challenge was strain specific. Shifts in microbiome profile occurred after pneumococcal exposure, and those volunteers who acquired carriage more often diverted from their original profile. S. pneumoniae was little prominent in the microbiome of pneumococcal carriers. Pneumococcal acquisition in healthy adults is more likely to occur in a diverse microbiome and appears to promote microbial heterogeneity.

Use Dose Bricks Concept to Implement Nasopharyngeal Carcinoma Treatment Planning

PubMed Central

Wu, Jia-Ming; Yu, Tsan-Jung; Yeh, Shyh-An; Chao, Pei-Ju; Huang, Chih-Jou

2014-01-01

Purpose. A “dose bricks” concept has been used to implement nasopharyngeal carcinoma treatment plan; this method specializes particularly in the case with bell shape nasopharyngeal carcinoma case. Materials and Methods. Five noncoplanar fields were used to accomplish the dose bricks technique treatment plan. These five fields include (a) right superior anterior oblique (RSAO), (b) left superior anterior oblique (LSAO), (c) right anterior oblique (RAO), (d) left anterior oblique (LAO), and (e) superior inferior vertex (SIV). Nondivergence collimator central axis planes were used to create different abutting field edge while normal organs were blocked by multileaf collimators in this technique. Results. The resulting 92% isodose curves encompassed the CTV, while maximum dose was about 115%. Approximately 50% volume of parotid glands obtained 10–15% of total dose and 50% volume of brain obtained less than 20% of total dose. Spinal cord receives only 5% from the scatter dose. Conclusions. Compared with IMRT, the expenditure of planning time and costing, “dose bricks” may after all be accepted as an optional implementation in nasopharyngeal carcinoma conformal treatment plan; furthermore, this method also fits the need of other nonhead and neck lesions if organ sparing and noncoplanar technique can be executed. PMID:24967395

Effect of edaravone on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma after radiotherapy: a randomized controlled trial.

PubMed

Tang, Yamei; Rong, Xiaoming; Hu, Weihan; Li, Guoqian; Yang, Xiaoxia; Yang, Jianhua; Xu, Pengfei; Luo, Jinjun

2014-11-01

Excessive generation of free radicals plays a critical role in the pathogenesis of radiation-induced brain injury. This study was designed to evaluate the protective effect of edaravone, a free radical scavenger, on radiation-induced brain necrosis in patients with nasopharyngeal carcinoma. Eligible patients were randomized 1:1 to the control group and the edaravone group (intravenous 30 mg twice per day for 2 weeks). Both groups received intravenous conventional steroid therapy and were monitored by brain MRI and LENT/SOMA scales prior to the entry of the trial and at 3-months after completing the trial. The primary end point was a 3-month response rate of the proportional changes determined by MRI. The trial is registered at Clinicaltrials.gov Identifier: NCT01865201. Between 2009 and 2012, we enrolled 154 patients. Of whom 137 were eligible for analysis. The volumes of necrosis estimated on T(2)-weighted image showed that 55.6 % edaravone-treated patients (40 out of 72) showed edema decreases ≥25 %, which was significantly higher than that in the control group (35.4 %, 23 out of 65, p = 0.025). Forty-four patients treated with edaravone (61.1 %) reported improvement in neurologic symptoms and signs evaluated by LENT/SOMA scales, while the rate was 38.5 % in the control group (p = 0.006). MRI of the edaravone group showed a significant decrease in area of T(1)-weighted contrast enhancement (1.67 ± 4.69 cm(2), p = 0.004) and the T(2)-weighted edema (5.08 ± 10.32 cm(2), p = 0.000). Moreover, compared with those in control group, patients with edaravone exhibited significantly better radiological improvement measured by T(2)-weighted image (p = 0.042). Administration of edaravone, in adjunct to steroid regimen, might provide a better outcome in patients with radiation-induced brain necrosis.

Identification of patients with nasopharyngeal carcinoma by serum protein profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

PubMed

Zhu, Xiao-Dong; Su, Fang; Liang, Zhong-Guo; Li, Ling; Qu, Song; Liang, Xia; Wang, Qi; Liang, Shi-Xiong; Chen, Long

2014-08-01

As diagnosis of nasopharyngeal carcinoma at an early disease stage is important, we attempted to distinguish between patients with nasopharyngeal carcinoma and noncancer controls by using serum protein profiles. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and CM10 protein chip were used to detect the serum proteomic patterns of 65 patients with nasopharyngeal carcinoma before radiotherapy and 93 noncancer controls. Proteomic spectra of serum samples from 50 nasopharyngeal carcinoma patients and 60 noncancer controls were used as a training set. The validity of the classification tree was then challenged with a blind test set which included another 15 patients with nasopharyngeal carcinoma and 33 noncancer controls. Biomarker Wizard 3.01 and Biomarker Pattern 5.01 were used in combination to analyze the data and to develop diagnostic models. 21 protein peaks were significantly different between nasopharyngeal carcinoma and controls. 4 mass peaks (M4182, M5343, M5913 and M8702 mass/charge ratio) were chosen automatically to construct a classification tree. The classification tree correctly determined 93.8 % (45/48) of the test samples with 93.3 % (14/15) of the nasopharyngeal carcinoma samples and 93.9 % (31/33) of the noncancer samples. Using a combination of serum protein profiles and Epstein-Barr viral capsid antigen immunoglobulin A antibody tests, the diagnostic sensitivity and specificity were increased to 100 and 97 %, respectively. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry could correctly distinguish nasopharyngeal carcinoma from noncancer individuals and showed great potential for the development of a screening test for the detection of nasopharyngeal carcinoma.

Antibiotic-induced dysbiosis alters host-bacterial interactions and leads to colonic sensory and motor changes in mice

PubMed Central

Aguilera, M; Cerdà-Cuéllar, M; Martínez, V

2015-01-01

Alterations in the composition of the commensal microbiota (dysbiosis) seem to be a pathogenic component of functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS), and might participate in the secretomotor and sensory alterations observed in these patients.We determined if a state antibiotics-induced intestinal dysbiosis is able to modify colonic pain-related and motor responses and characterized the neuro-immune mechanisms implicated in mice. A 2-week antibiotics treatment induced a colonic dysbiosis (increments in Bacteroides spp, Clostridium coccoides and Lactobacillus spp and reduction in Bifidobacterium spp). Bacterial adherence was not affected. Dysbiosis was associated with increased levels of secretory-IgA, up-regulation of the antimicrobial lectin RegIIIγ, and toll-like receptors (TLR) 4 and 7 and down-regulation of the antimicrobial-peptide Resistin-Like Molecule-β and TLR5. Dysbiotic mice showed less goblet cells, without changes in the thickness of the mucus layer. Neither macroscopical nor microscopical signs of inflammation were observed. In dysbiotic mice, expression of the cannabinoid receptor 2 was up-regulated, while the cannabinoid 1 and the mu-opioid receptors were down-regulated. In antibiotic-treated mice, visceral pain-related responses elicited by intraperitoneal acetic acid or intracolonic capsaicin were significantly attenuated. Colonic contractility was enhanced during dysbiosis. Intestinal dysbiosis induce changes in the innate intestinal immune system and modulate the expression of pain-related sensory systems, an effect associated with a reduction in visceral pain-related responses. Commensal microbiota modulates gut neuro-immune sensory systems, leading to functional changes, at least as it relates to viscerosensitivity. Similar mechanisms might explain the beneficial effects of antibiotics or certain probiotics in the treatment of IBS. PMID:25531553

Cone-Beam Computed Tomography Analysis of the Nasopharyngeal Airway in Nonsyndromic Cleft Lip and Palate Subjects.

PubMed

Al-Fahdawi, Mahmood Abd; Farid, Mary Medhat; El-Fotouh, Mona Abou; El-Kassaby, Marwa Abdelwahab

2017-03-01

  To assess the nasopharyngeal airway volume, cross-sectional area, and depth in previously repaired nonsyndromic unilateral cleft lip and palate versus bilateral cleft lip and palate patients compared with noncleft controls using cone-beam computed tomography with the ultimate goal of finding whether cleft lip and palate patients are more liable to nasopharyngeal airway obstruction.   A retrospective analysis comparing bilateral cleft lip and palate, unilateral cleft lip and palate, and control subjects. Significance at P ≤ .05.   Cleft Care Center and the outpatient clinic that are both affiliated with our faculty.   Cone-beam computed tomography data were selected of 58 individuals aged 9 to 12 years: 14 with bilateral cleft lip and palate and 20 with unilateral cleft lip and palate as well as 24 age- and gender-matched noncleft controls.   Volume, depth, and cross-sectional area of nasopharyngeal airway were measured.   Patients with bilateral cleft lip and palate showed significantly larger nasopharyngeal airway volume than controls and patients with unilateral cleft lip and palate (P < .001). Patients with bilateral cleft lip and palate showed significantly larger cross-sectional area than those with unilateral cleft lip and palate (P < .001) and insignificant cross-sectional area compared with controls (P > .05). Patients with bilateral cleft lip and palate showed significantly larger depth than controls and those with unilateral cleft lip and palate (P < .001). Patients with unilateral cleft lip and palate showed insignificant nasopharyngeal airway volume, cross-sectional area, and depth compared with controls (P > .05).   Unilateral and bilateral cleft lip and palate patients did not show significantly less volume, cross-sectional area, or depth of nasopharyngeal airway than controls. From the results of this study we conclude that unilateral and bilateral cleft lip and palate patients at the studied age and stage of repaired clefts are not

Sensitivity and specificity of narrow-band imaging nasoendoscopy compared to histopathology results in patients with suspected nasopharyngeal carcinoma

NASA Astrophysics Data System (ADS)

Adham, M.; Musa, Z.; Lisnawati; Suryati, I.

2017-08-01

Nasopharyngeal carcinoma (NPC) is a disease which is prevalent in developing countries like Indonesia. There were 164 new cases of nasopharyngeal carcinoma in the ear, nose, and throat (ENT) oncology outpatient clinic of the Cipto Mangunkusumo hospital in 2014, and 142 cases in 2015. Unfortunately, almost all of these cases presented at an advanced stage. The success of nasopharyngeal carcinoma treatment is largely determined by the stage when patients are diagnosed; it is critical to diagnose NPC as early as possible. Narrow-band imaging (NBI) is an endoscopic instrument with a light system that can improve the visualization of blood vessels of mucosal epithelial malignant tumors. NBI is expected to help clinicians to assess whether a lesion is malignant or not; to do so, it is important to know the value of sensitivity and specificity. This study is a cross-sectional form of a diagnostic test which was performed in the outpatient clinic of the ENT Head and Neck Surgery Department for the Cipto Mangunkusumo Hospital, from January to June 2016, and involved 56 subjects. Patients with a nasopharyngeal mass discovered by physical examination or imaging, and a suspected nasopharyngeal carcinoma were included as a subject. An NBI examination and biopsy was performed locally. Based on this research, NBI could be used as a screening tool for nasopharyngeal carcinoma with high sensitivity (100%), but with a low specificity result (6.7%).

Interactions between the colonic transcriptome, metabolome, and microbiome in mouse models of obesity-induced intestinal cancer.

PubMed

Pfalzer, Anna C; Kamanu, Frederick K; Parnell, Laurence D; Tai, Albert K; Liu, Zhenhua; Mason, Joel B; Crott, Jimmy W

2016-08-01

Obesity is a significant risk factor for colorectal cancer (CRC); however, the relative contribution of high-fat (HF) consumption and excess adiposity remains unclear. It is becoming apparent that obesity perturbs both the intestinal microbiome and metabolome, and each has the potential to induce protumorigenic changes in the epithelial transcriptome. The physiological consequences and the degree to which these different biologic systems interact remain poorly defined. To understand the mechanisms by which obesity drives colonic tumorigenesis, we profiled the colonic epithelial transcriptome of HF-fed and genetically obese (DbDb) mice with a genetic predisposition to intestinal tumorigenesis (Apc(1638N)); 266 and 584 genes were differentially expressed in the colonic mucosa of HF and DbDb mice, respectively. These genes mapped to pathways involved in immune function, and cellular proliferation and cancer. Furthermore, Akt was central within the networks of interacting genes identified in both gene sets. Regression analyses of coexpressed genes with the abundance of bacterial taxa identified three taxa, previously correlated with tumor burden, to be significantly correlated with a gene module enriched for Akt-related genes. Similarly, regression of coexpressed genes with metabolites found that adenosine, which was negatively associated with inflammatory markers and tumor burden, was also correlated with a gene module enriched with Akt regulators. Our findings provide evidence that HF consumption and excess adiposity result in changes in the colonic transcriptome that, although distinct, both appear to converge on Akt signaling. Such changes could be mediated by alterations in the colonic microbiome and metabolome.

NASOPHARYNGEAL CONCENTRATIONS IN THE HUMAN VOLUNTEER BREATHING ACETONE

EPA Science Inventory

In an effort to examine the absorption of a common chemical into the nasopharyngeal region in humans, a 57 year old male volunteer inhaled uniformly labeled 13C-acetone at 1.4 ppm for 30 min while performing different breathing maneuvers; nose inhale, nose exhale (NINE); mouth ...

Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH.

PubMed

Urosevic, Jelena; Garcia-Albéniz, Xabier; Planet, Evarist; Real, Sebastián; Céspedes, María Virtudes; Guiu, Marc; Fernandez, Esther; Bellmunt, Anna; Gawrzak, Sylwia; Pavlovic, Milica; Mangues, Ramon; Dolado, Ignacio; Barriga, Francisco M; Nadal, Cristina; Kemeny, Nancy; Batlle, Eduard; Nebreda, Angel R; Gomis, Roger R

2014-07-01

The mechanisms that allow colon cancer cells to form liver and lung metastases, and whether KRAS mutation influences where and when metastasis occurs, are unknown. We provide clinical and molecular evidence showing that different MAPK signalling pathways are implicated in this process. Whereas ERK2 activation provides colon cancer cells with the ability to seed and colonize the liver, reduced p38 MAPK signalling endows cancer cells with the ability to form lung metastasis from previously established liver lesions. Downregulation of p38 MAPK signalling results in increased expression of the cytokine PTHLH, which contributes to colon cancer cell extravasation to the lung by inducing caspase-independent death in endothelial cells of the lung microvasculature. The concerted acquisition of metastatic traits in the colon cancer cells together with the sequential colonization of liver and lung highlights the importance of metastatic lesions as a platform for further dissemination.

Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

PubMed Central

2011-01-01

Background Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. Methods The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. Results BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. Conclusions These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent. PMID:21864401

15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis.

PubMed

Myung, Seung-Jae; Rerko, Ronald M; Yan, Min; Platzer, Petra; Guda, Kishore; Dotson, Angela; Lawrence, Earl; Dannenberg, Andrew J; Lovgren, Alysia Kern; Luo, Guangbin; Pretlow, Theresa P; Newman, Robert A; Willis, Joseph; Dawson, Dawn; Markowitz, Sanford D

2006-08-08

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a prostaglandin-degrading enzyme that is highly expressed in normal colon mucosa but is ubiquitously lost in human colon cancers. Herein, we demonstrate that 15-PGDH is active in vivo as a highly potent suppressor of colon neoplasia development and acts in the colon as a required physiologic antagonist of the prostaglandin-synthesizing activity of the cyclooxygenase 2 (COX-2) oncogene. We first show that 15-PGDH gene knockout induces a marked 7.6-fold increase in colon tumors arising in the Min (multiple intestinal neoplasia) mouse model. Furthermore, 15-PGDH gene knockout abrogates the normal resistance of C57BL/6J mice to colon tumor induction by the carcinogen azoxymethane (AOM), conferring susceptibility to AOM-induced adenomas and carcinomas in situ. Susceptibility to AOM-induced tumorigenesis is mediated by a marked induction of dysplasia, proliferation, and cyclin D1 expression throughout microscopic aberrant crypt foci arising in 15-PGDH null colons and is concomitant with a doubling of prostaglandin E(2) in 15-PGDH null colonic mucosa. A parallel role for 15-PGDH loss in promoting the earliest steps of colon neoplasia in humans is supported by our finding of a universal loss of 15-PGDH expression in microscopic colon adenomas recovered from patients with familial adenomatous polyposis, including adenomas as small as a single crypt. These models thus delineate the in vivo significance of 15-PGDH-mediated negative regulation of the COX-2 pathway and moreover reveal the particular importance of 15-PGDH in opposing the neoplastic progression of colonic aberrant crypt foci.

Interleukin-6 (IL-6) mediated the increased contraction of distal colon in streptozotocin-induced diabetes in rats via IL-6 receptor pathway

PubMed Central

Chang, Xin-Wen; Qin, Ying; Jin, Zhi; Xi, Tao-Fang; Yang, Xiao; Lu, Ze-Hao; Tang, Yu-Ping; Cai, Wen-Ting; Chen, Shao-Jun; Xie, Dong-Ping

2015-01-01

Colonic dysmotility occurs in diabetes and blood plasma interleukin (IL)-6 levels are significantly elevated in type 1 diabetes mellitus. The aim of this study was to investigate whether IL-6 and the IL-6 receptor pathway mediates colonic dysfunction in type 1 diabetes mellitus. Male SD rats were treated with a single intraperitoneally injected dose of streptozotocin (STZ), and those displaying sustained high blood glucose were selected as diabetes mellitus models. Longitudinal muscle strips of colon were prepared to monitor colonic contraction in vitro. Contractile responses of strips of colon were recorded following treatment with IL-6 in control animals, and following anti IL-6 antibody treatment in STZ-induced diabetes in rats. Concentration of IL-6 in plasma and colon were determined by ELISA. Expressions of IL-6 α-receptor and IL-6 β-receptor in colon tissues were determined by immunohistochemistry or Western blot analysis. The non-diabetes rats treated with IL-6 and the untreated diabetes rats showed increased contraction of distal colon, whereas the diabetes rats treated with anti-IL-6 antibody showed decreased contraction of distal colon compared with the untreated diabetes rats. The IL-6 levels of plasma but not colon increased in diabetes rats. The expression of IL-6 α-receptor increased in diabetes rats. These results indicate that diabetes rats show an increase in the contractions of distal colon partly via the IL-6-IL-6 receptor pathway. PMID:26191141

Combination of curcumin and green tea catechins prevents dimethylhydrazine-induced colon carcinogenesis.

PubMed

Xu, Gang; Ren, Guijie; Xu, Xia; Yuan, Huiqing; Wang, Zhenzheng; Kang, Ludong; Yu, Wenguang; Tian, Keli

2010-01-01

The chemopreventive effects of curcumin and green tea catechins individually and in combination on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis were studied in male Wister rats following 32 weeks of dietary treatment. The incidence, number and size of colorectal cancer were measured. Colorectal aberrant crypt foci (ACF) were analyzed by methylene blue staining. Proliferation indices and apoptotic indices were determined by PCNA immunostaining and TUNEL assay, respectively. The results showed that dietary curcumin, catechins and combination administration significantly inhibited the total number of ACF per rat. The combination treatment displayed the most potent inhibitory effect, while there was no difference of inhibition between curcumin and catechins-treated groups. The incidence of colorectal cancer in the treated groups was significantly lower than that of positive control group. Compared with the positive control group, the proliferation index was significantly decreased and the apoptotic index was significantly increased in all treatment groups, while the effect of the combination was the greatest among the treated groups. Our findings suggest that the combination of curcumin and catechins may produce a synergistic colon cancer-preventative effect that would be more potent than each of the compounds alone. Copyright 2009 Elsevier Ltd. All rights reserved.

Apoptosis and expression of cytokines triggered by pyropheophorbide-a methyl ester-mediated photodynamic therapy in nasopharyngeal carcinoma cells.

PubMed

Li, K M; Sun, X; Koon, H K; Leung, W N; Fung, M C; Wong, R N S; Lung, Maria L; Chang, C K; Mak, N K

2006-12-01

The photodynamic properties of pyropheophorbide-a methyl ester (MPPa), a semi-synthetic photosensitizer derived from chlorophyll a, were evaluated in a human nasopharyngeal carcinoma HONE-1 cell line. MPPa was non-toxic to the HONE-1. At the concentrations of 0.5-2μM, MPPa-mediated a drug dose-dependent photocytotoxicity in the HONE-1 cells. Confocal microscopy revealed a subcellular localization of MPPa in mitochondria and the Golgi apparatus. MPPa PDT-induced apoptosis was associated with the collapse of mitochondrial membrane potential, release of cytochrome c, the up-regulation of endoplasmic reticulum (ER) stress proteins (calnexin, Grp 94 and Grp78), and the activation of caspases-3 and -9. The photocytotoxicity was reduced by the corresponding specific caspase inhibitors. MPPa PDT-treated HONE-1 cells also up-regulated the gene expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and beta-chemokines (MIP-1β, MPIF-1, and MPIF-2). These results suggest that the MPPa may be developed as a chlorophyll-based photosensitizer for the treatment of nasopharyngeal carcinoma.

Elevated expression of CD93 promotes angiogenesis and tumor growth in nasopharyngeal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bao, Lili; Tang, Mingming; Zhang, Qicheng

2016-08-05

CD93, also known as the complement component C1q receptor (C1qRp), has been reported to promote the progression of some cancer types. However, the expression and physiological significance of CD93 in nasopharyngeal carcinoma (NPC) remain largely elusive. In this study, we first examined the expression of CD93 in NPC and experimentally manipulated its expression. We observed that vascular CD93 expression is elevated in NPC and is correlated with T classification, N classification, distant metastasis, clinical stage and poor prognosis (all P < 0.05). In addition, overexpression of CD93 promoted angiogenesis in vitro. What’s more, we found that CD93 was highly expressed in NPC tissuesmore » and cells, and the regulation of CD93 on cell proliferation was determined by cell counting kit (CCK)-8 assay and cell cycle analyses. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as CD93 to improve NPC treatment. -- Highlights: •This is the first research about the relationship between CD93 and nasopharyngeal carcinoma. •We explored the prognostic significance of vascular CD93 expression in nasopharyngeal carcinoma. •We researched on angiogenesis and cell proliferation of nasopharyngeal carcinoma and how CD93 affected them.« less

[Endoscopic transnasal approach for nasopharyngeal angiofibroma without arterial embolism].

PubMed

Yang, Donghui; Qiu, Qianhui; Liang, Minzhi; Tan, Xianggao; Xia, Guangsheng

2014-01-01

To explore the feasibility of endoscopic resection without arterial embolism for nasopharyngeal angiofibroma and the strategy of decreasing the bleeding during the operation. The clinical data of twenty-five cases of nasopharyngeal angiofibroma were retrospective analyzed, including 3 cases of Radowski stageIIa, 5 cases of stageIIb, 4 cases of stageIIc and with 13 cases of stage IIIa. All cases did not receive the arterial embolism, and controlled hypotension were adopted under endoscopic transnasal approach during the tumor resection. Two cases were added the labiogingival incision. During the operation, under the opening vision, cutting out the outside of the infratemporal fossa, and the pterygoid process to adequate exposure the pterygopalatine fossa and infratemporal fossa.Early recognition of anatomical landmarks and establish the safety plane, along the periphery of the tumor to proceed with micro-separation, early blocking tumor nutrient vessels, en bloc resection of the tumor and some other ways to reduce bleeding and tumor resection. Amount of bleeding during operation was 600-1500 ml, none of them had internal carotid artery injury and intracranial injury or some other complication.Follow-up 2-3 years was available in all patients, except 1 case with residual of tumor surrounding the optic nerve, the other 24 cases had no residual tumor and relapses. The preoperative occlusion and artery ligation may not be needed.Surgical technique is the key to reduce blood loss, and it is feasible to have endoscopic resection of nasopharyngeal angiofibroma with proper operating technique.

The pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea-pig.

PubMed Central

Marcus, S. N.; Marcus, A. J.; Marcus, R.; Ewen, S. W.; Watt, J.

1992-01-01

The pre-ulcerative phase of carrageenan-induced colonic ulceration was investigated in guinea-pigs supplied 3% degraded carrageenan as an aqueous solution as drinking fluid for 2 or 3 days during which no ulceration of the bowel was observed with the naked eye or dissecting microscope. Mucosal microscopic changes, from caecum to rectum, were multifocal and included cellular infiltrates, dilatation of glands, crypt abscesses, micro-ulcers and sulphated polysaccharide in the lamina propria. Sulphated polysaccharide was also demonstrated histologically for the first time within the surface epithelium and showed ultrastructural features similar to carrageenan. The results indicate that colonic epithelium in the guinea-pig is capable of macromolecular absorption. Carrageenan, a highly active polyanionic electrolyte, within the surface epithelial cells is most likely a primary factor in the breakdown of mucosal integrity. Macromolecular absorption causing enteropathy of the large bowel is a new pathophysiological concept which may have implications in man, particularly in the pathology of large bowel disease. Images Fig. 7 Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1356411

Increased production of BDNF in colonic epithelial cells induced by fecal supernatants from diarrheic IBS patients.

PubMed

Wang, Peng; Chen, Fei-Xue; Du, Chao; Li, Chang-Qing; Yu, Yan-Bo; Zuo, Xiu-Li; Li, Yan-Qing

2015-05-22

Colonic brain-derived neurotrophic factor (BDNF) plays an essential role in pathogenesis of abdominal pain in diarrhea-predominant irritable bowel syndrome (IBS-D), but regulation on its expression remains unclear. We investigated the role of fecal supernatants (FSN) from IBS-D patients on regulating BDNF expression in colonic epithelial cells of human and mice. Using human Caco-2 cells, we found that IBS-D FSN significantly increased BDNF mRNA and protein levels compared to control FSN, which were remarkably suppressed by the serine protease inhibitor. To further explore the potential mechanisms, we investigated the impact of protease-activated receptor-2 (PAR-2) on BDNF expression. We found a significant increase in PAR-2 expression in Caco-2 after IBS-D FSN stimulation. Knockdown of PAR-2 significantly inhibited IBS-D FSN-induced upregulation of BDNF. Moreover, we found that phosphorylation of p38 MAPK, not NF-κB p65, contributed to PAR-2-mediated BDNF overexpression. To confirm these results, we intracolonically infused IBS-D or control FSN in mice and found that IBS-D FSN significantly elevated colonic BDNF and visceral hypersensitivity in mice, which were both suppressed by the inhibitor of serine protease or antagonist of PAR-2. Together, our data indicate that activation of PAR-2 signaling by IBS-D FSN promotes expression of colonic BDNF, thereby contributing to IBS-like visceral hypersensitivity.

Fermentation supernatants of Lactobacillus delbrueckii inhibit growth of human colon cancer cells and induce apoptosis through a caspase 3-dependent pathway.

PubMed

Wan, Ying; Xin, Yi; Zhang, Cuili; Wu, Dachang; Ding, Dapeng; Tang, Li; Owusu, Lawrence; Bai, Jing; Li, Weiling

2014-05-01

Probiotic bacteria are known to exert a wide range of beneficial effects on their animal hosts. Therefore, the present study explored the effect of the supernatants obtained from Lactobacillus delbrueckii fermentation (LBF) on colon cancer. The results indicated that the proliferation of LBF solution-treated colon cancer SW620 cells was arrested and accumulated in the G1 phase in a concentration-dependent manner. The LBF solution efficiently induced apoptosis through the intrinsic caspase 3-depedent pathway, with a corresponding decreased expression of Bcl-2. The activity of matrix metalloproteinase 9, which is associated with the invasion of colon cancer cells, was also decreased in the LBF-treated cells. In conclusion, the results demonstrate the antitumor effect of LBF in vitro and may contribute to the development of novel therapies for the treatment of colon cancer.

One patient - three head and neck primaries: nasopharyngeal, tongue and thyroid cancers

PubMed Central

2013-01-01

Background We report a rare case of three head and neck malignancies in one patient. Squamous cell carcinoma of tongue and papillary thyroid carcinoma occurred as metachronous cancers in a patient with primary nasopharyngeal carcinoma. These three pathologically distinct malignancies of head and neck region in one patient is a rare phenomenon and is not reported so far. Case presentation A 60 year old Saudi female patient presented in March 2011 with locally advanced nasopharyngeal carcinoma. After completion of concurrent chemoradiation in June 2011, she developed two new primaries i-e thyroid cancer and tongue cancer in May 2012 along with recurrent nasopharyngeal carcinoma. We discuss histopathologic features, diagnostic tools and treatment modalities for this rarely existing case. Conclusion High index of suspicion and thorough work up is essential in follow up of patients with head and neck primary cancers. The effect of field cancerization and environmental factors need to be explored in greater depths in such selected cases. However, which patients are at increased risk of triplet primaries, is still unknown. PMID:24164964

Strawberry-Tree Honey Induces Growth Inhibition of Human Colon Cancer Cells and Increases ROS Generation: A Comparison with Manuka Honey

PubMed Central

Afrin, Sadia; Forbes-Hernandez, Tamara Y.; Gasparrini, Massimiliano; Bompadre, Stefano; Quiles, José L.; Sanna, Gavino; Spano, Nadia; Giampieri, Francesca; Battino, Maurizio

2017-01-01

Honey is a natural product known to modulate several biological activities including cancer. The aim of the present study was to examine the phytochemical content and the antioxidant activity of Strawberry tree (Arbutus unedo) honey (STH) and its cytotoxic properties against human colon adenocarcinoma (HCT-116) and metastatic (LoVo) cell lines in comparison with Manuka (Leptospermum scoparium) honey (MH). Several unifloral STH and MH were analyzed for their phenolic, flavonoid, amino acid and protein contents, as well as their radical scavenging activities. STH from the Berchidda area showed the highest amount of phenolic, flavonoid, amino acid and protein content, and antioxidant capacity compared to MH. Both STH and MH induced cytotoxicity and cell death in a dose- and time-dependent manner in HCT-116 and LoVo cells, with less toxicity on non-cancer cells. Compared to MH, STH showed more effect at lower concentrations on HCT-116 and LoVo cells. In addition, both honeys increased intracellular reactive oxygen species (ROS) generation. In HCT-116 cells, STH and MH induced similar ROS production but in LoVo cells STH induced a higher percentage of ROS compared to MH. Our results indicate that STH and MH can induce cell growth inhibition and ROS generation in colon adenocarcinoma and metastatic cells, which could be due to the presence of phytochemicals with antioxidant properties. These preliminary results are interesting and suggest a potential chemopreventive action which could be useful for further studies in order to develop chemopreventive agents for colon cancer. PMID:28287469

Prevalence of Methicillin-Resistant Staphylococcus aureus from Equine Nasopharyngeal and Guttural Pouch Wash Samples.

PubMed

Boyle, A G; Rankin, S C; Duffee, L A; Morris, D

2017-09-01

Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as a cause of nosocomial infections in both human and veterinary medicine. Studies that examine the nasopharynx and guttural pouches of the horse as carriage sites for MRSA have not been reported. MRSA colonizes the nasopharynx and guttural pouch of horses. To determine the prevalence of MRSA in equine nasopharyngeal wash (NPW) and guttural pouch lavage (GPL) samples in a field population of horses. One hundred seventy-eight samples (123 NPW and 55 GPL) from 108 horses. Prospective study. Samples were collected from a convenience population of clinically ill horses with suspected Streptococcus equi subsp. equi (S. equi) infection, horses convalescing from a known S. equi infection, and asymptomatic horses undergoing S. equi screening. Samples were submitted for S. aureus aerobic bacterial culture with mannitol salt broth and two selective agars (cefoxitin CHROMagar as the PBP2a inducer and mannitol salt agar with oxacillin). Biochemical identification of Staphylococcus species and pulsed-field gel electrophoresis (PFGE), to determine clonal relationships between isolates, were performed. Methicillin-resistant Staphylococcus (MRS) was isolated from the nasopharynx of 7/108 (4%) horses. Three horses had MRSA (2.7%), and 4 had MR-Staphylococcus pseudintermedius (MRSP). MRSA was isolated from horses on the same farm. PFGE revealed the 3 MRSA as USA 500 strains. Sampling the nasopharynx and guttural pouch of community-based horses revealed a similarly low prevalence rate of MRSA as other studies sampling the nares of community-based horses. More study is required to determine the need for sampling multiple anatomic sites when screening horses for MRSA. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Diet-induced obesity elevates colonic TNF-α in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer✩

PubMed Central

Liu, Zhenhua; Brooks, Ryan S.; Ciappio, Eric D.; Kim, Susan J.; Crott, Jimmy W.; Bennett, Grace; Greenberg, Andrew S.; Mason, Joel B.

2014-01-01

Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induced elevation of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Animal studies were conducted on C57BL/6 mice, and obesity was induced by utilizing a high-fat diet (60% kcal). An inflammation-specific microarray was performed, and results were confirmed with real-time polymerase chain reaction. The array revealed that diet-induced obesity increased the expression of TNF-α in the colon by 72% (P=.004) and that of interleukin-18 by 41% (P=.023). The concentration of colonic TNF-α protein, determined by ex vivo culture assay, was nearly doubled in the obese animals (P=.002). The phosphorylation of glycogen synthase kinase 3 beta (GSK3β), an important intermediary inhibitor of Wnt signaling and a potential target of TNF-α, was quantitated by immunohistochemistry. The inactivated (phosphorylated) form of GSK3β was elevated in the colonic mucosa of obese mice (P<.02). Moreover, β-catenin, the key effector of canonical Wnt signaling, was elevated in the colons of obese mice (P<.05), as was the expression of a downstream target gene, c-myc (P<.05). These data demonstrate that diet-induced obesity produces an elevation in colonic TNF-α and instigates a number of alterations of key components within the Wnt signaling pathway that are protransformational in nature. Thus, these observations offer evidence for a biologically plausible avenue, the Wnt pathway, by which obesity increases the risk of colorectal cancer. PMID:22209007

Childhood Nasopharyngeal Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Treatment options for children with nasopharyngeal cancer include combined-modality therapy with chemotherapy and radiation. Surgery has a limited role because the disease is usually considered unresectable due to extensive local spread. Get detailed treatment information in this clinician summary.

Colonic motor dysfunctions in a mouse model of high-fat diet-induced obesity: an involvement of A2B adenosine receptors.

PubMed

Antonioli, Luca; Pellegrini, Carolina; Fornai, Matteo; Tirotta, Erika; Gentile, Daniela; Benvenuti, Laura; Giron, Maria Cecilia; Caputi, Valentina; Marsilio, Ilaria; Orso, Genny; Bernardini, Nunzia; Segnani, Cristina; Ippolito, Chiara; Csóka, Balázs; Németh, Zoltán H; Haskó, György; Scarpignato, Carmelo; Blandizzi, Corrado; Colucci, Rocchina

2017-12-01

Adenosine A 2B receptors (A 2B R) regulate several enteric functions. However, their implication in the pathophysiology of intestinal dysmotility associated with high-fat diet (HFD)-induced obesity has not been elucidated. We investigated the expression of A 2B R in mouse colon and their role in the mechanisms underlying the development of enteric dysmotility associated with obesity. Wild-type C57BL/6J mice were fed with HFD (60% kcal from fat) or normocaloric diet (NCD; 18% kcal from fat) for 8 weeks. Colonic A 2B R localization was examined by immunofluorescence. The role of A 2B R in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs). In NCD mice, A 2B R were predominantly located in myenteric neurons; in HFD animals, their expression increased throughout the neuromuscular layer. Functionally, the A 2B R antagonist MRS1754 enhanced electrically induced NK 1 -mediated tachykininergic contractions in LMPs from HFD mice, while it was less effective in tissues from NCD mice. The A 2B receptor agonist BAY 60-6583 decreased colonic tachykininergic contractions in LMPs, with higher efficacy in preparations from obese mice. Both A 2B R ligands did not affect contractions elicited by exogenous substance P. Obesity is related with a condition of colonic inflammation, leading to an increase of A 2B R expression. A 2B R, modulating the activity of excitatory tachykininergic nerves, participate to the enteric dysmotility associated with obesity.

Clinical Outcomes of 174 Nasopharyngeal Carcinoma Patients With Radiation-Induced Temporal Lobe Necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, Tai-Chung, E-mail: lamtaichung@gmail.com; Wong, Frank C.S.; Leung, To-Wai

Purpose: To retrospectively study the clinical outcomes of nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis (TLN) treated with steroids, surgery, or observation only. Methods and Patients: We performed a retrospective analysis of 174 consecutive patients diagnosed with TLN between 1990 and 2008. Before 1998, symptomatic patients were treated with oral steroids, while asymptomatic patients were treated conservatively. After 1998, most symptomatic and asymptomatic patients with a large volume of necrosis were treated by intravenously pulsed-steroid therapy with a standardized protocol. We examined factors affecting grade 4 complication-free survival and overall survival. Outcomes of the three treatment groups, those receivingmore » conservative treatment, those receiving oral steroid, and those receiving intravenous pulse steroid, were compared. Results: The mean follow-up time was 115 months. Rates of grade 4 complication-free survival at 2 years and at 5 years after diagnosis of TLN were 72.2% and 54.1%, respectively. The 2-year and 5-year overall survival rates were 57.5% and 35.4%, respectively. Multivariate analysis revealed that being symptomatic at diagnosis (relative risk [RR], 4.5; p = 0.0001), re-irradiation of the nasopharynx (NP) (RR, 1.56; p = 0.008), salvage brachytherapy to the NP (RR, 1.75; p = 0.012), and a short latency period before the diagnosis of TLN (RR, 0.96, p < 0.0001) were independent prognosticators of poor grade 4 complication-free survival. Patients with all four factors had a 100% risk of developing grade 4 complications within 5 years; whereas if no factor was present, the risk was 12.5%. Intravenous pulse steroid therapy was associated with a higher clinical response rate compared with conventional steroid therapy (p < 0.0001); however, it did not affect complication-free survival in multivariate analysis. Conclusions: TLN patients with good prognosticators could be observed without active treatment

ROLE OF SURGICAL APPROACHES INFLUENCING TUMOUR RECURRENCE IN NASOPHARYNGEAL ANGIOFIBROMA.

PubMed

Muhammad, Raza; Hussain, Altaf; Rehman, Fazal; Iqbal, Johar; Khan, Munib; Ullah, Gohar; Khan, Zakir

2015-01-01

Juvenile nasopharyngeal angiofibroma (JNA) is an uncommon tumour constituting less than 1% of all head & neck tumours. This tumour has an aggressive local behaviour if left untreated. Surgery is the mainstay of treatment with no common consensus on a single approach. Tumour stage and surgical approaches are the major determinants of outcome. The objective of this study was to evaluate the influence of surgical approaches on tumour recurrence in patients with nasopharyngeal angiofibroma. This descriptive study was conducted in the Department of ENT and Head and Neck Surgery, PIMS, Islamabad and Ayub Medical Institution, Abbottabad from Jan 2010 to Jan 2014 consisting of 34 diagnosed cases of nasopharyngeal angiofibroma. All patients were treated surgically while radiotherapy was given in a few. All patients were followed up for one year. Among 34 patients, 25 were treated by lateral rhinotomy approach with medial maxillectomy, 5 by mid-facial degloving approach and 3 by transpalatine approach. One patient with cavernous sinus involvement was treated by radiotherapy. Patients were followed up for one year both by clinical examination and imaging if needed. Recurrence was found in 15% (5/33) patients and postop radiotherapy was given to them. Lateral rhinotomy approach with medial maxillectomy is highly effective even in advanced stage JNA for complete removal of the disease. Postoperative radiotherapy is an effective adjuvant.

Early discrimination of nasopharyngeal carcinoma based on tissue deoxyribose nucleic acid surface-enhanced Raman spectroscopy analysis

NASA Astrophysics Data System (ADS)

Qiu, Sufang; Li, Chao; Lin, Jinyong; Xu, Yuanji; Lu, Jun; Huang, Qingting; Zou, Changyan; Chen, Chao; Xiao, Nanyang; Lin, Duo; Chen, Rong; Pan, Jianji; Feng, Shangyuan

2016-12-01

Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573 cm-1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.8%, 92.3%, and 87.9% for early NPC, advanced NPC, and normal nasopharyngeal tissue DNA, respectively. In this exploratory study, we demonstrated the potential of SERS for early detection of NPC based on the DNA molecular study of biopsy tissues.

Weight loss following diet-induced obesity does not alter colon tumorigenesis in the AOM mouse model.

PubMed

Velázquez, Kandy T; Enos, Reilly T; Carson, Meredith S; Cranford, Taryn L; Bader, Jackie E; Chatzistamou, Ioulia; Singh, Udai P; Nagarkatti, Prakash S; Nagarkatti, Mitzi; Davis, J Mark; Carson, James A; Murphy, E Angela

2016-10-01

Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity. Subsequently, azoxymethane (AOM) was used to promote colon and liver carcinogenesis. A subset of obese mice was then switched to a low-fat diet (LFD) containing 67.5% carbohydrate, 12.2% fat, and 20% protein to promote intentional weight loss. Body weight loss and excess fat reduction did not protect mice from colon cancer progression and liver dysplastic lesion in the AOM-chemical-cancer model even though these mice had improved blood glucose and leptin levels. Intentional weight loss in AOM-treated mice actually produced histological changes that resemble dysplastic alterations in the liver and presented a higher percentage of F4/80 + CD206 + macrophages and activated T cells (CD4 + CD69 + ) in the spleen and lymph nodes, respectively. In addition, the liver of AOM-treated mice exposed to a HFD during the entire period of the experiment exhibited a marked increase in proliferation and pNF-κB activation. Altogether, these data suggest that intentional weight loss following chemical-induced carcinogenesis does not affect colon tumorigenesis but may in fact negatively impact liver repair mechanisms. Copyright © 2016 the American Physiological Society.

Monte Carlo evaluation of Acuros XB dose calculation Algorithm for intensity modulated radiation therapy of nasopharyngeal carcinoma

NASA Astrophysics Data System (ADS)

Yeh, Peter C. Y.; Lee, C. C.; Chao, T. C.; Tung, C. J.

2017-11-01

Intensity-modulated radiation therapy is an effective treatment modality for the nasopharyngeal carcinoma. One important aspect of this cancer treatment is the need to have an accurate dose algorithm dealing with the complex air/bone/tissue interface in the head-neck region to achieve the cure without radiation-induced toxicities. The Acuros XB algorithm explicitly solves the linear Boltzmann transport equation in voxelized volumes to account for the tissue heterogeneities such as lungs, bone, air, and soft tissues in the treatment field receiving radiotherapy. With the single beam setup in phantoms, this algorithm has already been demonstrated to achieve the comparable accuracy with Monte Carlo simulations. In the present study, five nasopharyngeal carcinoma patients treated with the intensity-modulated radiation therapy were examined for their dose distributions calculated using the Acuros XB in the planning target volume and the organ-at-risk. Corresponding results of Monte Carlo simulations were computed from the electronic portal image data and the BEAMnrc/DOSXYZnrc code. Analysis of dose distributions in terms of the clinical indices indicated that the Acuros XB was in comparable accuracy with Monte Carlo simulations and better than the anisotropic analytical algorithm for dose calculations in real patients.

Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κB and COX-2 signaling.

PubMed

Zhuang, Mingzhu; Zhao, Mouming; Qiu, Huijuan; Shi, Dingbo; Wang, Jingshu; Tian, Yun; Lin, Lianzhu; Deng, Wuguo

2014-01-01

Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC) cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate) had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-κB/COX-2 (lipopolysaccharides) abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-κB and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma.

Glucosinolates from pak choi and broccoli induce enzymes and inhibit inflammation and colon cancer differently.

PubMed

Lippmann, Doris; Lehmann, Carsten; Florian, Simone; Barknowitz, Gitte; Haack, Michael; Mewis, Inga; Wiesner, Melanie; Schreiner, Monika; Glatt, Hansruedi; Brigelius-Flohé, Regina; Kipp, Anna P

2014-06-01

High consumption of Brassica vegetables is considered to prevent especially colon carcinogenesis. The content and pattern of glucosinolates (GSLs) can highly vary among different Brassica vegetables and may, thus, affect the outcome of Brassica intervention studies. Therefore, we aimed to feed mice with diets containing plant materials of the Brassica vegetables broccoli and pak choi. Further enrichment of the diets by adding GSL extracts allowed us to analyze the impact of different amounts (GSL-poor versus GSL-rich) and different patterns (broccoli versus pak choi) of GSLs on inflammation and tumor development in a model of inflammation-triggered colon carcinogenesis (AOM/DSS model). Serum albumin adducts were analyzed to confirm the up-take and bioactivation of GSLs after feeding the Brassica diets for four weeks. In agreement with their high glucoraphanin content, broccoli diets induced the formation of sulforaphane-lysine adducts. Levels of 1-methoxyindolyl-3-methyl-histidine adducts derived from neoglucobrassicin were the highest in the GSL-rich pak choi group. In the colon, the GSL-rich broccoli and the GSL-rich pak choi diet up-regulated the expression of different sets of typical Nrf2 target genes like Nqo1, Gstm1, Srxn1, and GPx2. GSL-rich pak choi induced the AhR target gene Cyp1a1 but did not affect Ugt1a1 expression. Both colitis and tumor number were drastically reduced after feeding the GSL-rich pak choi diet while the other three diets had no effect. GSLs can act anti-inflammatory and anti-carcinogenic but both effects depend on the specific amount and pattern of GSLs within a vegetable. Thus, a high Brassica consumption cannot be generally considered to be cancer-preventive.

Enhanced endocytosis of nano-curcumin in nasopharyngeal cancer cells: An atomic force microscopy study

NASA Astrophysics Data System (ADS)

Prasanth, R.; Nair, Greshma; Girish, C. M.

2011-10-01

Recent studies in drug development have shown that curcumin can be a good competent due to its improved anticancer, antioxidant, anti-proliferative, and anti-inflammatory activities. A detailed real time characterization of drug (curcumin)-cell interaction is carried out in human nasopharyngeal cancer cells using atomic force microscopy. Nanocurcumin shows an enhanced uptake over micron sized drugs attributed to the receptor mediated route. Cell membrane stiffness plays a critical role in the drug endocytosis in nasopharyngeal cancer cells.

Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dheer, Rishu; Patterson, Jena; Dudash, Mark

Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low)more » or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals

Association between functional antibody against Group B Streptococcus and maternal and infant colonization in a Gambian cohort.

PubMed

Le Doare, Kirsty; Faal, Amadou; Jaiteh, Mustapha; Sarfo, Francess; Taylor, Stephen; Warburton, Fiona; Humphries, Holly; Birt, Jessica; Jarju, Sheikh; Darboe, Saffiatou; Clarke, Edward; Antonio, Martin; Foster-Nyarko, Ebenezer; Heath, Paul T; Gorringe, Andrew; Kampmann, Beate

2017-05-19

Vertical transmission of Group B Streptococcus (GBS) is a prerequisite for early-onset disease and a consequence of maternal GBS colonization. Disease protection is associated with maternally-derived anti-GBS antibody. Using a novel antibody-mediated C3b/iC3b deposition flow cytometry assay which correlates with opsonic killing we developed a model to assess the impact of maternally-derived functional anti-GBS antibody on infant GBS colonization from birth to day 60-89 of life. Rectovaginal swabs and cord blood (birth) and infant nasopharyngeal/rectal swabs (birth, day 6 and day 60-89) were obtained from 750 mother/infant pairs. Antibody-mediated C3b/iC3b deposition with cord and infant sera was measured by flow cytometry. We established that as maternally-derived anti-GBS functional antibody increases, infant colonization decreases at birth and up to three months of life, the critical time window for the development of GBS disease. Further, we observed a serotype (ST)-dependent threshold above which no infant was colonized at birth. Functional antibody above the upper 95th confidence interval for the geometric mean concentration was associated with absence of infant GBS colonization at birth for STII (p<0.001), STIII (p=0.01) and STV (p<0.001). Increased functional antibody was also associated with clearance of GBS between birth and day 60-89. Higher concentrations of maternally-derived antibody-mediated complement deposition are associated with a decreased risk of GBS colonization in infants up to day 60-89 of life. Our findings are of relevance to establish thresholds for protection following vaccination of pregnant women with future GBS vaccines. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Diet-induced obesity elevates colonic TNF-α in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer.

PubMed

Liu, Zhenhua; Brooks, Ryan S; Ciappio, Eric D; Kim, Susan J; Crott, Jimmy W; Bennett, Grace; Greenberg, Andrew S; Mason, Joel B

2012-10-01

Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induced elevation of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Animal studies were conducted on C57BL/6 mice, and obesity was induced by utilizing a high-fat diet (60% kcal). An inflammation-specific microarray was performed, and results were confirmed with real-time polymerase chain reaction. The array revealed that diet-induced obesity increased the expression of TNF-α in the colon by 72% (P=.004) and that of interleukin-18 by 41% (P=.023). The concentration of colonic TNF-α protein, determined by ex vivo culture assay, was nearly doubled in the obese animals (P=.002). The phosphorylation of glycogen synthase kinase 3 beta (GSK3β), an important intermediary inhibitor of Wnt signaling and a potential target of TNF-α, was quantitated by immunohistochemistry. The inactivated (phosphorylated) form of GSK3β was elevated in the colonic mucosa of obese mice (P<.02). Moreover, β-catenin, the key effector of canonical Wnt signaling, was elevated in the colons of obese mice (P<.05), as was the expression of a downstream target gene, c-myc (P<.05). These data demonstrate that diet-induced obesity produces an elevation in colonic TNF-α and instigates a number of alterations of key components within the Wnt signaling pathway that are protransformational in nature. Thus, these observations offer evidence for a biologically plausible avenue, the Wnt pathway, by which obesity increases the risk of colorectal cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Therapeutic implications of Epstein–Barr virus infection for the treatment of nasopharyngeal carcinoma

PubMed Central

Hutajulu, Susanna Hilda; Kurnianda, Johan; Tan, I Bing; Middeldorp, Jaap M

2014-01-01

Nasopharyngeal carcinoma (NPC) is highly endemic in certain regions including the People’s Republic of China and Southeast Asia. Its etiology is unique and multifactorial, involving genetic background, epigenetic, and environment factors, including Epstein–Barr virus (EBV) infection. The presence of EBV in all tumor cells, aberrant pattern of antibodies against EBV antigens in patient sera, and elevated viral DNA in patient circulation as well as nasopharyngeal site underline the role of EBV during NPC development. In NPC tumors, EBV expresses latency type II, where three EBV-encoded proteins, Epstein–Barr nuclear antigen 1, latent membrane protein 1 and 2 (LMP1, 2), are expressed along with BamH1-A rightward reading frame 1, Epstein–Barr virus-encoded small nuclear RNAs, and BamH1-A rightward transcripts. Among all encoded proteins, LMP1 plays a central role in the propagation of NPC. Standard treatment of NPC consists of radiotherapy with or without chemotherapy for early stage, concurrent chemoradiotherapy in locally advanced tumors, and palliative systemic chemotherapy in metastatic disease. However, this standard care has limitations, allowing recurrences and disease progression in a certain proportion of cases. Although the pathophysiological link and molecular process of EBV-induced oncogenesis are not fully understood, therapeutic approaches targeting the virus may increase the cure rate and add clinical benefit. The promising results of early phase clinical trials on EBV-specific immunotherapy, epigenetic therapy, and treatment with viral lytic induction offer new options for treating NPC. PMID:25228810

Optogenetic Activation of Colon Epithelium of the Mouse Produces High-Frequency Bursting in Extrinsic Colon Afferents and Engages Visceromotor Responses.

PubMed

Makadia, Payal A; Najjar, Sarah A; Saloman, Jami L; Adelman, Peter; Feng, Bin; Margiotta, Joseph F; Albers, Kathryn M; Davis, Brian M

2018-06-20

Epithelial cells of the colon provide a vital interface between the internal environment (lumen of the colon) and colon parenchyma. To examine epithelial-neuronal signaling at this interface, we analyzed mice in which channelrhodopsin (ChR2) was targeted to either TRPV1-positive afferents or to villin-expressing colon epithelial cells. Expression of a ChR2-EYFP fusion protein was directed to either primary sensory neurons or to colon epithelial cells by crossing Ai32 mice with TRPV1-Cre or villin-Cre mice, respectively. An ex vivo preparation of the colon was used for single-fiber analysis of colon sensory afferents of the pelvic nerve. Afferents were characterized using previously described criteria as mucosal, muscular, muscular-mucosal, or serosal and then tested for blue light-induced activation. Light activation of colon epithelial cells produced robust firing of action potentials, similar to that elicited by physiologic stimulation (e.g., circumferential stretch), in 50.5% of colon afferents of mice homozygous for ChR2 expression. Light-induced activity could be reduced or abolished in most fibers using a cocktail of purinergic receptor blockers suggesting ATP release by the epithelium contributed to generation of sensory neuron action potentials. Using electromyographic recording of visceromotor responses we found that light stimulation of the colon epithelium evoked behavioral responses in Vil-ChR2 mice that was similar to that seen with balloon distension of the colon. These ex vivo and in vivo data indicate that light stimulation of colon epithelial cells alone, without added mechanical or chemical stimuli, can directly activate colon afferents and elicit behavioral responses. SIGNIFICANCE STATEMENT Abdominal pain that accompanies inflammatory diseases of the bowel is particularly vexing because it can occur without obvious changes in the structure or inflammatory condition of the colon. Pain reflects abnormal sensory neuron activity that may be

Anticarcinogenic efficacy of phytic acid extracted from rice bran on azoxymethane-induced colon carcinogenesis in rats.

PubMed

Norazalina, S; Norhaizan, M E; Hairuszah, I; Norashareena, M S

2010-05-01

This study is carried out to determine the potential of phytic acid extracted from rice bran in the suppression of colon carcinogenesis induced by azoxymethane (AOM) in rats. Seventy-two male Sprague-Dawley rats were divided into 6 groups with 12 rats in each group. The intended rats for cancer treatment received two intraperitoneal injections of AOM in saline (15mg/kg bodyweight) over a 2-week period. The treatments of phytic acid were given in two concentrations: 0.2% (w/v) and 0.5% (w/v) during the post-initiation phase of carcinogenesis phase via drinking water. The colons of the animals were analyzed for detection and quantification of aberrant crypt foci (ACF) after 8 weeks of treatment. The finding showed treatment with 0.2% (w/v) extract phytic acid (EPA) gave the greatest reduction in the formation of ACF. In addition, phytic acid significantly suppressed the number of ACF in the distal, middle and proximal colon as compared to AOM alone (p<0.05). For the histological classification of ACF, treatment with 0.5% (w/v) commercial phytic acid (CPA) had the highest percentage (71%) of non-dysplastic ACF followed by treatment with 0.2% (w/v) EPA (61%). Administration of phytic acid also reduced the incidence and multiplicity of total tumors even though there were no significant differences between groups. In conclusion, this study found the potential value of phytic acid extracted from rice bran in reducing colon cancer risk in rats.

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma

PubMed Central

Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-01-01

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased (P < 0.001, = 0.001, and < 0.001, respectively), but all other ADC histogram parameters increased (all P < 0.001, except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid volume continued to decrease (P = 0.022), and SD, 75th and 90th percentiles continued to increase (P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADCmean, ADCmin, kurtosis, and 25th, 50th, 75th, 90th percentiles (from time point 1 to 2) correlated with late parotid atrophy rate (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis revealed correlations among parotid volume, time point, and ADC histogram parameters. Early mean change rates for bilateral parotid SD and ADCmax could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 (P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy. PMID:29050274

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma.

PubMed

Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-19

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased ( P < 0.001, = 0.001, and < 0.001, respectively), but all other ADC histogram parameters increased (all P < 0.001, except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid volume continued to decrease ( P = 0.022), and SD, 75 th and 90 th percentiles continued to increase ( P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADC mean , ADC min , kurtosis, and 25 th , 50 th , 75 th , 90 th percentiles (from time point 1 to 2) correlated with late parotid atrophy rate (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis revealed correlations among parotid volume, time point, and ADC histogram parameters. Early mean change rates for bilateral parotid SD and ADC max could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 ( P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy.

Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

PubMed

Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran

2017-02-01

Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Local oral immunization with synthetic peptides induces a dual mucosal IgG and salivary IgA antibody response and prevents colonization of Streptococcus mutans.

PubMed Central

Lehner, T; Haron, J; Bergmeier, L A; Mehlert, A; Beard, R; Dodd, M; Mielnik, B; Moore, S

1989-01-01

A small cell surface antigen of Streptococcus mutans was partially sequenced and the amino terminal peptides of 11, 15 and 20 amino acid residues and a dimer of the 15 and 20 residues peptides were synthesized. The synthetic peptides (SP) were used in topical oral immunization of the gingivomucosal epithelium of macaque monkeys. Sequential examination for antibodies over a period of up to 30 weeks revealed that six applications of the linear or cyclized SP11 and a random SP11 induced negligible or very low antibody levels. In contrast, the SP17 (SP15 with added cysteine at each terminus), SP21 (SP20 with one cysteine) and the dimer (SP35) induced significant anti-SP as well as anti-native streptococcal antibodies in the gingival fluid and in saliva. The functional significance of this immune response was examined by studying its effect on oral colonization of S. mutans following feeding of a carbohydrate-rich diet. Whereas control animals, sham-immunized with a random SP of 11 residues, showed increased colonization of the teeth by S. mutans, there was no colonization or a significant reduction in colonization of animals immunized with the cyclized SP17, linear SP21 or dimerized SP35. These experiments suggest that local immunization with SP derived from the sequences of a streptococcal cell surface antigen induce a dual local immune response of gingival IgG and salivary IgA antibodies against the SP and native SA. These antibodies may be involved in preventing colonization of S. mutans, which is the principal agent in the development of dental caries. PMID:2759661

Inhibitory effect of natural coumarin compounds, esculetin and esculin, on oxidative DNA damage and formation of aberrant crypt foci and tumors induced by 1,2-dimethylhydrazine in rat colons.

PubMed

Kaneko, Takao; Tahara, Shoichi; Takabayashi, Fumiyo

2007-11-01

The effects of esculetin (6,7-dihydroxycoumarin) and its 6-glycoside, esculin, on 8-oxo-2'-deoxyguanosine (8-oxodG) formation and carcinogenesis induced by a chemical carcinogen, 1,2-dimethylhydrazine (DMH), were examined in the colons of male Fischer 344 rats. Animals were given water containing esculetin or esculin for 7 d before subcutaneous injection of DMH (20 mg/kg body wt), killed 24 h after DMH treatment, and the levels of thiobarbituric acid reactive substances (TBARS) and 8-oxodG in the colons were determined. Both esculetin and esculin suppressed significantly the DMH-induced increases in 8-oxodG and TBARS in rat colon mucosa. We further investigated the modifying effect of esculin intake on the development of DMH-induced colonic aberrant crypt foci (ACF). Animals were given DMH once a week for 4 weeks to induce ACF. They then received water containing esculin ad libitum for 5 weeks (initiation phase) or 11 weeks after DMH treatment (post-initiation phase). Animals in the positive control group received tap water throughout the experiment. At the end of the experiment (16 weeks), the ingestion of esculin during the initiation phase significantly reduced the incidence of gross tumors, the number of ACF per rat and the mean number of AC per focus, while the esculin treatment during the post-initiation phase significantly decreased only the number of ACF per rat. These results suggest that esculin intake has an inhibitory effect on DMH-induced oxidative DNA damage and carcinogenesis in rat colons.

5-Methoxyflavanone induces cell cycle arrest at the G2/M phase, apoptosis and autophagy in HCT116 human colon cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shin, Soon Young; Department of Biomedical Science and Technology, Research Center for Transcription Control, Konkuk University, Seoul 143-701; Hyun, Jiye

2011-08-01

Natural flavonoids have diverse pharmacological activities, including anti-oxidative, anti-inflammatory, and anti-cancer activities. In this study, we investigated the molecular mechanism underlying the action of 5-methoxyflavanone (5-MF) which has a strong bioavailability and metabolic stability. Our results show that 5-MF inhibited the growth and clonogenicity of HCT116 human colon cancer cells, and that it activated DNA damage responses, as revealed by the accumulation of p53 and the phosphorylation of DNA damage-sensitive proteins, including ataxia-telangiectasia mutated (ATM) at Ser1981, checkpoint kinase 2 (Chk2) at Thr68, and histone H2AX at Ser139. 5-MF-induced DNA damage was confirmed in a comet tail assay. We alsomore » found that 5-MF increased the cleavage of caspase-2 and -7, leading to the induction of apoptosis. Pretreatment with the ATM inhibitor KU55933 enhanced 5-MF-induced {gamma}-H2AX formation and caspase-7 cleavage. HCT116 cells lacking p53 (p53{sup -/-}) or p21 (p21{sup -/-}) exhibited increased sensitivity to 5-MF compared to wild-type cells. 5-MF further induced autophagy via an ERK signaling pathway. Blockage of autophagy with the MEK inhibitor U0126 potentiated 5-MF-induced {gamma}-H2AX formation and caspase-2 activation. These results suggest that a caspase-2 cascade mediates 5-MF-induced anti-tumor activity, while an ATM/Chk2/p53/p21 checkpoint pathway and ERK-mediated autophagy act as a survival program to block caspase-2-mediated apoptosis induced by 5-MF. - Graphical abstract: Display Omitted Highlights: > 5-MF inhibits the proliferation of HCT116 colon cancer cells. > 5-MF inhibits cell cycle progression and induces apoptosis. > Inhibition of autophagy triggers 5-MF-induced apoptosis. > Inhibition of ERK signaling blocks 5-MF-induced autophagy but activates apoptosis. > Treatment with 5-MF in combination with an ERK inhibitor may be a potential therapeutic strategy in human colon cancer.« less

HIV Exposure to the Epithelia in Ectocervical and Colon Tissues Induces Inflammatory Cytokines Without Tight Junction Disruption

PubMed Central

Sankapal, Soni; Gupta, Phalguni; Ratner, Deena; Ding, Ming; Shen, Chengli; Sanyal, Anwesha; Stolz, Donna; Cu-Uvin, Susan; Ramratnam, Bharat

2016-01-01

Abstract Epithelial cells in human cervical and colonic mucosa do not express HIV receptor. However, HIV transmission occurs across the unbreached epithelia by an unknown mechanism. In this study, the effect of HIV exposure on tight junction (TJ) and cytokine production in ectocervical and colon mucosal epithelia in tissue biopsies was investigated in an organ culture model. After HIV exposure, the distribution patterns and quantities of epithelial TJ and adherens proteins were evaluated by immunofluorescence staining followed by confocal microscopy. Cytokine mRNA in the mucosal epithelia was also evaluated by real-time reverse transcription–polymerase chain reaction (RT-PCR). HIV transmission was evaluated by measuring p24 production in culture supernatant. Our results showed there were no significant changes in the distribution and quantities of epithelial TJ/adherens junction (AJ) proteins after exposure to HIV. However, higher levels of CXCL10 and CXCL11 mRNA expression were detected in HIV-exposed ectocervical epithelia. In case of colon mucosa, higher levels of CXCL10 and IL-6 mRNA expression were detected in HIV-exposed colon mucosa. Our study suggests that HIV induces cytokine production in epithelial cells, which may facilitate HIV transmission by recruiting HIV target cells in the submucosal region. Furthermore, HIV transmission may not occur through epithelial TJ/AJ disruption. PMID:27153934

High-fat Western diet-induced obesity contributes to increased tumor growth in mouse models of human colon cancer.

PubMed

O'Neill, Ann Marie; Burrington, Christine M; Gillaspie, Erin A; Lynch, Darin T; Horsman, Melissa J; Greene, Michael W

2016-12-01

Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth. Homozygous Rag1 tm1Mom mice were fed either a low-fat Western diet or a high-fat Western diet (HFWD), then human colon cancer xenografts were implanted subcutaneously or orthotopically. Tumors were analyzed to detect changes in receptor tyrosine kinase-mediated signaling and expression of inflammatory-associated genes in epididymal white adipose tissue. In both models, mice fed an HFWD weighed more and had increased intra-abdominal fat, and tumor weight was greater compared with in the low-fat Western diet-fed mice. They also displayed significantly higher levels of leptin; however, there was a negative correlation between leptin levels and tumor size. In the orthotopic model, tumors and adipose tissue from the HFWD group displayed significant increases in both c-Jun N-terminal kinase activation and monocyte chemoattractant protein 1 expression, respectively. In conclusion, this study suggests that human colon cancer growth is accelerated in animals that are obese and insulin resistant due to the consumption of an HFWD. Copyright © 2016 Elsevier Inc. All rights reserved.

Automated Ki-67 Quantification of Immunohistochemical Staining Image of Human Nasopharyngeal Carcinoma Xenografts.

PubMed

Shi, Peng; Zhong, Jing; Hong, Jinsheng; Huang, Rongfang; Wang, Kaijun; Chen, Yunbin

2016-08-26

Nasopharyngeal carcinoma is one of the malignant neoplasm with high incidence in China and south-east Asia. Ki-67 protein is strictly associated with cell proliferation and malignant degree. Cells with higher Ki-67 expression are always sensitive to chemotherapy and radiotherapy, the assessment of which is beneficial to NPC treatment. It is still challenging to automatically analyze immunohistochemical Ki-67 staining nasopharyngeal carcinoma images due to the uneven color distributions in different cell types. In order to solve the problem, an automated image processing pipeline based on clustering of local correlation features is proposed in this paper. Unlike traditional morphology-based methods, our algorithm segments cells by classifying image pixels on the basis of local pixel correlations from particularly selected color spaces, then characterizes cells with a set of grading criteria for the reference of pathological analysis. Experimental results showed high accuracy and robustness in nucleus segmentation despite image data variance. Quantitative indicators obtained in this essay provide a reliable evidence for the analysis of Ki-67 staining nasopharyngeal carcinoma microscopic images, which would be helpful in relevant histopathological researches.

Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis.

PubMed

Touil, Yasmine; Igoudjil, Wassila; Corvaisier, Matthieu; Dessein, Anne-Frédérique; Vandomme, Jérôme; Monté, Didier; Stechly, Laurence; Skrypek, Nicolas; Langlois, Carole; Grard, Georges; Millet, Guillaume; Leteurtre, Emmanuelle; Dumont, Patrick; Truant, Stéphanie; Pruvot, François-René; Hebbar, Mohamed; Fan, Fan; Ellis, Lee M; Formstecher, Pierre; Van Seuningen, Isabelle; Gespach, Christian; Polakowska, Renata; Huet, Guillemette

2014-02-15

Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery. We show that a clonal 5F31 cell population, resistant to 1 μmol/L 5FU, express a typical cancer stem cell-like phenotype and enter into a reversible quiescent G0 state upon reexposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, YES1 silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP transcript levels positively correlated with colon cancer relapse and shorter patient survival (P < 0.05 and P < 0.025, respectively). We identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer. ©2013 AACR

Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis

PubMed Central

Touil, Yasmine; Igoudjil, Wassila; Corvaisier, Matthieu; Dessein, Anne-Frédérique; Vandomme, Jérôme; Monté, Didier; Stechly, Laurence; Skrypek, Nicolas; Langlois, Carole; Grard, Georges; Millet, Guillaume; Leteurtre, Emmanuelle; Dumont, Patrick; Truant, Stéphanie; Pruvot, François-René; Hebbar, Mohamed; Fan, Fan; Ellis, Lee M.; Formstecher, Pierre; Van Seuningen, Isabelle; Gespach, Christian; Polakowska, Renata; Huet, Guillemette

2015-01-01

Purpose Metastasis and drug resistance are the major limitations in the survival and management of cancer patients. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of colon cancer patients with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery. Results We show that a clonal 5F31 cell population, resistant to 1μM 5FU, express a typical cancer stem cell-like phenotype and enter into a reversible quiescent G0-state upon re-exposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, c-Yes silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, c-Yes and YAP transcript levels were higher in liver metastases of colon cancer patients after 5FU-based neoadjuvant chemotherapy. Moreover, the c-Yes and YAP levels positively correlated with colon cancer relapse and shorter patient survival (p<0.05 and p<0.025, respectively). Conclusions We identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer. PMID:24323901

Characterization of the EP receptor types that mediate longitudinal smooth muscle contraction of human colon, mouse colon and mouse ileum.

PubMed

Fairbrother, S E; Smith, J E; Borman, R A; Cox, H M

2011-08-01

Prostaglandin E(2) (PGE(2) ) is an inflammatory mediator implicated in several gastrointestinal pathologies that affect normal intestinal transit. The aim was to establish the contribution of the four EP receptor types (EP(1-4) ), in human colon, that mediate PGE(2) -induced longitudinal smooth muscle contraction. Changes in isometric muscle tension of human colon, mouse colon and mouse ileum were measured in organ baths in response to receptor-specific agonists and antagonists. In addition, lidocaine was used to block neurogenic activity to investigate whether EP receptors were pre- or post-junctional. PGE(2) contracted longitudinal muscle from human and mouse colon and mouse ileum. These contractions were inhibited by the EP(1) receptor antagonist, EP(1) A in human colon, whereas a combination of EP(1) A and the EP(3) antagonist, L798106 inhibited agonist responses in both mouse preparations. The EP(3) agonist, sulprostone also increased muscle tension in both mouse tissues, and these responses were inhibited by lidocaine in the colon but not in the ileum. Although PGE(2) consistently contracted all three muscle preparations, butaprost decreased tension by activating smooth muscle EP(2) receptors in both colonic tissues. Alternatively, in mouse ileum, butaprost responses were lidocaine-sensitive, suggesting that it was activating prejunctional EP(2) receptors on inhibitory motor neurons. Conversely, EP(4) receptors were not functional in all the intestinal muscle preparations tested. PGE(2) -induced contraction of longitudinal smooth muscle is mediated by EP(1) receptors in human colon and by a combination of EP(1) and EP(3) receptors in mouse intestine, whereas EP(2) receptors modulate relaxation in all three preparations. © 2011 Blackwell Publishing Ltd.

Habitual Consumption of Soy Products and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study

PubMed Central

Liu, Yuan-ting; Fan, Yu-ying; Xu, Chun-hua; Lin, Xiao-ling; Lu, Yun-kai; Zhang, Xing-lan; Zhang, Cai-xia; Chen, Yu-ming

2013-01-01

Background and Objectives Many studies have shown a negative association between the consumption of soy products and the risk of some cancers, but little is known about the effect of soy consumption on nasopharyngeal carcinoma. We assessed the association between the consumption of soy products on nasopharyngeal carcinoma risk in Chinese individuals. Methods This case-control study included 600 (448 males and 152 females) incident cases of nasopharyngeal carcinoma, and an equal number of controls, matched according to gender, age (± 3 y) and household type to the nasopharyngeal carcinoma cases. All subjects were recruited from hospitals in Guangzhou, China. A face-to-face interview was conducted with each study individual to collect general information and habitual dietary intake using a 78-item quantitative food-frequency questionnaire. Odds ratios and their 95% confidence intervals were estimated using conditional logistic regression analyses. Results The median intakes of soy foods (in protein) were 0.5/0.5, 1.4/1.7, 2.7/3.3 and 6.1/7.7 (male/female) g/d in the quartiles 1 to 4. Both univariate and multivariate analyses showed no significant association between the consumption of soy proteins or soy isoflavones and the risk of nasopharyngeal carcinoma. The adjusted odds ratios (95% confidence intervals) between extreme quartiles were 0.97 (0.66-1.45) for soy proteins and 0.97 (0.66-1.42) for total isoflavones. Null associations were also observed between intake of the individual isoflavones daidzein, genistein and glycitein and NPC risk, with adjusted odds ratios for the extreme quartiles ranging between 0.73 and 1.23. Conclusion Habitual consumption of soy products had no significant effect on the risk of nasopharyngeal carcinoma in Chinese adults with a relatively low intake. PMID:24155974

Intermittent intussusception caused by colonic lipoma.

PubMed

Chan, K C; Lin, N H; Lien, H C; Chan, S L; Yu, S C

1998-01-01

Colonic lipomas are rare, usually small, and occur most often in the right colon, particularly in the cecum. They are most common in elderly women. Intermittent episodes of intussusception are not uncommon in patients with colonic lipoma, but they are usually caused by larger pedunculated lipomas. We report a 43-year-old woman with a large colonic submucosal lipoma that induced intermittent colocolic intussusception. The patient presented with symptoms of peptic ulcer, including intractable upper abdominal pain, which did not resolve with treatment. Abdominal sonography showed typical findings of intussusception caused by a lipoma, but the manifestations on barium enema and computed tomography mimicked a malignant colonic tumor. The patient's abdominal pain disappeared after right hemicolectomy and the tumor was demonstrated to be a lipoma. The postoperative course was uneventful; there was no evidence of recurrence at follow-up 6 months later. Physicians should be aware that surrounding organs should also be evaluated in cases of chronic peptic ulcer with intractable upper abdominal pain.

Trigeminocardiac reflex during endoscopic juvenile nasopharyngeal angiofibroma surgery: an appraisal.

PubMed

Sharma, Shilpee Bhatia; Janakiram, Trichy Narayanan; Baxi, Hina; Chinnasamy, Balamurugan

2017-07-01

Juvenile nasopharyngeal angiofibroma is a locally aggressive benign tumour which has propensity to erode the skull base. The tumour spreads along the pathways of least resistance and is in close proximity to the extracranial part of trigeminal nerve. Advancements in expanded approaches for endoscopic excision of tumours in infratemporal fossa and pterygopalatine fossa increase the vulnerability for the trigeminocardiac reflex. The manipulation of nerve and its branches during tumour dissection can lead to sensory stimulation and thus inciting the reflex. The aim of our study is to report the occurrence of trigeminocardiac reflex in endoscopic excision of juvenile nasopharyngeal angiofibroma. To describe the occurence of trigeminocardiac reflex during endoscopic endonasal excision of juvenile nasopharyngeal angiofibroma. We studied the occurrence of TCR in 15 patients (out of 242 primary cases and 52 revision cases) operated for endoscopic endonasal excision of JNA. The drop in mean arterial blood pressure and heart rate were observed and measured. To the best of our knowledge of English literature, this is the first case series reporting TCR as complication in endoscopic excision of JNA. occurence of this reflex has been mentioned in various occular, maxillofacial surgeries but its occurence during endoscopic excision of JNA has never been reported before. Manifestation of trigeminocardiac reflex during surgery can alter the course of the surgery and is a potential threat to life. It is essential for the anesthetist and surgeons to be familiar with the presentations, preventive measures and management protocols.

Dextran Sulfate Sodium-Induced Colonic Histopathology, but not Altered Epithelial Ion Transport, Is Reduced by Inhibition of Phosphodiesterase Activity

PubMed Central

Diaz-Granados, Natalia; Howe, Kathryn; Lu, Jun; McKay, Derek M.

2000-01-01

Inhibition of phosphodiesterase (PDE) activity is beneficial in models of arthritis and airway inflammation. Here we assessed the ability of PDE inhibitors to modulate colitis by exposing mice to 4% (w/v) dextran sulfate sodium (DSS) drinking water for 5 days with or without rolipram, an inhibitor of PDE type 4, or the nonselective PDE inhibitor, pentoxifylline (both at 5 mg/kg, i.p., twice daily). Controls received saline, vehicle, or drug only. Colonic histology, myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels, and epithelial ion transport (baseline and stimulated by electrical nerve stimulation, carbachol, and forskolin) were examined. DSS-treated mice displayed a variable diarrhea, significant histopathology in the mid-distal colon, elevated MPO activity, and reduced (>50%) responses to all three pro-secretory stimuli. Treatment with rolipram, and to a lesser extent pentoxifylline, significantly reduced the severity of the colonic histopathology and MPO levels. Neither PDE inhibitor had any affect on the diminished ion transport events caused by DSS-induced colitis. However, although stimulated ion transport events were still reduced 3 days after DSS treatment, colonic segments from DSS + rolipram-treated mice displayed enhanced recovery in their secretory responsiveness, particularly to carbachol. These findings indicate that specific PDE4 inhibition can significantly reduce the tissue damage that accompanies colitis and enhance recovery of normal colonic function. PMID:10854237

Heme-Induced Biomarkers Associated with Red Meat Promotion of colon Cancer Are Not Modulated by the Intake of Nitrite

PubMed Central

Chenni, Fatima Z; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Hobbs, Ditte A; Kunhle, Gunter G C; Pierre, Fabrice H; Corpet, Denis E

2013-01-01

Red and processed meat consumption is associated with the risk of colorectal cancer. Three hypotheses are proposed to explain this association, via heme/alcenal, heterocyclic amines or N-nitroso compounds. Rats have often been used to study these hypotheses, but the lack of enterosalivary cycle of nitrate in rats casts doubt on the relevance of this animal model to predict nitroso- and heme-associated human colon carcinogenesis. The present study was thus designed to clarify whether a nitrite intake that mimics the enterosalivary cycle can modulate heme-induced nitrosation and fat peroxidation. This study shows that, in contrast with the starting hypothesis, salivary nitrite did not change the effect of hemoglobin on biochemical markers linked to colon carcinogenesis, notably lipid peroxidation and cytotoxic activity in the colon of rat. However, ingested sodium nitrite increased fecal nitroso-compounds level, but their fecal concentration and their nature (iron-nitrosyl) would not be associated with an increased risk of cancer. The rat model could thus be relevant to study the effect of red meat on colon carcinogenesis in spite of the lack of nitrite recycling in rat’s saliva. PMID:23441609

Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation.

PubMed

Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B

2010-02-01

Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood. Published by Elsevier Ltd.

Investigation of mitigating effect of colon-specific prodrugs of boswellic acid on 2,4,6-trinitrobenzene sulfonic acid-induced colitis in Wistar rats: Design, kinetics and biological evaluation

PubMed Central

Sarkate, Ajinkya; Dhaneshwar, Suneela S

2017-01-01

AIM To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. METHODS Synthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces. The prodrugs were screened in TNBS-induced colitis modeled Wistar rats. Statistical significance was assumed at P < 0.05, P < 0.01, P < 0.001 when compared with disease controls using one-way and two-way ANOVAs. RESULTS Prodrugs were stable in 0.05 mol/L HCl buffer (pH 1.2) and stomach homogenates. Negligible hydrolysis was observed in phosphate buffer and intestinal homogenates. Substantial release (55%-72% and 68%-86%) of BBA was achieved in rat fecal matter and homogenates of colon. In vivo studies of BBA with L-tryptophan (BT) authenticated colon-specific release of BBA. But, surprisingly substantial concentration of BBA was seen to reach the systemic circulation due to probable absorption through colonic mucosa. Site-specifically enhanced bioavailability of BBA could be achieved in colon, which resulted in demonstration of significant mitigating effect on TNBS-induced colitis in rats without inducing any adverse effects on stomach, liver and pancreas. Prodrug of BT was found to be 1.7% (P < 0.001) superior than sulfasalazine in reducing the inflammation to colon among all prodrugs tested. CONCLUSION The outcome of this study strongly suggests that these prodrugs might have dual applicability to inflammatory bowel disease and chronotherapy of rheumatoid arthritis. PMID:28275295

Effects of nasal instillation of a nitric oxide-releasing solution or parenteral administration of tilmicosin on the nasopharyngeal microbiota of beef feedlot cattle at high-risk of developing respiratory tract disease.

PubMed

Timsit, E; Workentine, M; Crepieux, T; Miller, C; Regev-Shoshani, G; Schaefer, A; Alexander, T

2017-12-01

Nitric oxide has bactericidal and virucidal properties. Nasal instillation of a nitric oxide releasing solution (NORS) on arrival at the feedlot was recently reported as inferior to a parenteral injection of tilmicosin (macrolide antibiotic) for control of bovine respiratory disease (BRD) in cattle at high-risk of developing BRD. We hypothesized that this inferiority was due to differences between treatments with regards to their effects on the nasopharyngeal microbiota. The objective was to compare nasal instillation of NORS versus parenteral administration of tilmicosin regarding their effects on the nasopharyngeal microbiota of feedlot cattle at high-risk of developing BRD. Culture-independent community profiling (16S rRNA sequencing) and culture-based methods were used to evaluate treatment effects. High-risk Angus-cross heifers (n=20) were randomly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for prevention of BRD. Heifers were sampled using guarded deep nasal swabs immediately prior to treatment (day 0) and on days 1, 5 and 10 after treatment. Based on culture-independent community profiling, there was a distinct shift in composition of the nasopharyngeal microbiota during the first 10 d after arrival, with 116 OTUs changing over time, but no difference between treatment groups. However, culture-based methods detected a difference between treatment groups, with more cattle culture-positive for Pasteurellaceae in the NORS group at day 5 post-treatment. This difference in ability to inhibit colonization of the nasopharynx by Pasteurellaceae may be the basis for NORS being inferior to tilmicosin for control of BRD in high-risk cattle. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inducible Intestine-specific Deletion Of Krüppel-Like Factor 5 Is Characterized By A Regenerative Response In Adult Mouse Colon

PubMed Central

Nandan, Mandayam O.; Ghaleb, Amr M.; Liu, Yang; Bialkowska, Agnieszka B.; McConnell, Beth B.; Shroyer, Kenneth R.; Robine, Sylvie

2014-01-01

Krüppel-like factor 5 (KLF5) is a pro-proliferative transcriptional regulator primarily expressed in the intestinal crypt epithelial cells. Constitutive intestine-specific deletion of Klf5 is neonatal lethal suggesting a crucial role for KLF5 in intestinal development and homeostasis. We have previously shown Klf5 to play an active role regulating intestinal tumorigenesis. Here we examine the effect of inducible intestine-specific deletion of Klf5 in adult mice. Klf5 is lost from the intestine beginning at day 3 after the start of a 5-day treatment with the inducer tamoxifen. Although the mice have no significant weight loss or lethality, the colonic tissue shows signs of epithelial distress starting at day 3 following induction. Accompanying the morphological changes is a significant loss of proliferative crypt epithelial cells as revealed by BrdU or Ki67 staining at days 3 & 5 after start of tamoxifen. We also observed a loss of goblet cells from the colon and Paneth cells from the small intestine upon induced deletion of Klf5. In addition, loss of Klf5 from the colonic epithelium is accompanied by a regenerative response that coincides with an expansion in the zone of Sox9 expression along the crypt axis. At day 11, both proliferation and Sox9 expression return to baseline levels. Microarray and quantitative PCR analyses reveal an upregulation of several regeneration-associated genes (Reg1A, Reg3G and Reg3B) and down-regulation of many Klf5 targets (Ki-67, cyclin B, Cdc2 and cyclin D1). Sox9 and Reg1A protein levels are also increased upon Klf5 loss. Lentiviral-mediated knockdown of KLF5 and exogenous expression of KLF5 in colorectal cancer cell lines confirm that Sox9 expression is negatively regulated by KLF5. Furthermore, ChIP assays reveal a direct association of KLF5 with both the Sox9 and Reg1A promoters. We have shown that disruption of epithelial homeostasis due to Klf5 loss from the adult colon is followed by a regenerative response led by Sox9 and the

Industrial Pollutants and Nasopharyngeal Cancer: An Open Question.

PubMed

Menicagli, Roberto; Bolla, Gianni; Menicagli, Laura; Esseiridou, Anastassia

2017-05-01

Nasopharyngeal Carcinoma represents 0.7% of the total cancer cases in the world with an ASR index of 1.7 and is widely associated with Epstein-Barr virus. It is not common in Italy (ASR index of 0.5) while in China (ASR 1.9), one third of the clinical cases are observed in Guangdong (ASR index 11.3). It is also quite common in Malaysia and Indonesia. The activation of the cancerogenesis process happens after the exposure to some environmental parameters that epidemiological studies have indicated with various dietary habits, mainly for salted fish consumption. The purpose of this work is to highlight such as exposure to compounds, such as formaldehyde, which is present in the different working conditions of these countries and may lead to the real cause to establish the carcinogenic process. The most recent publications regarding the impact of various external factors on Pub Med, Google, TOXLINE, Chem Abstract, were analyzed with the radiological data that were found in Milan hospitals database. The relationship between food consumption and nasopharyngeal cancer are not clear and statistically insignificant in Indonesia. In Malaysia, the preparation of natural rubber for the use of formaldehyde is a dangerous environmental factor. The same exposure is a risk factor in Guangdong, where many workers are employed in the wood panel industry. Incidence of cancer in these Chinese ethnic groups decreases when they migrate to other countries. In the last 5 years, few cases were recorded in Italy, without any apparent change in ethnic environmental factors or HBV infection Discussion: In the production of natural rubber, a lot of people are exposed to formaldehyde during the various steps of preparation and production such as stripping, drying and coagulation without observing proper environmental hygiene precautions. The same working conditions are present in industrial production of wood panels in Guangdong, China. The relationship between exposure to formaldehyde and

NSC 95397 Suppresses Proliferation and Induces Apoptosis in Colon Cancer Cells through MKP-1 and the ERK1/2 Pathway.

PubMed

Dubey, Navneet Kumar; Peng, Bou-Yue; Lin, Chien-Min; Wang, Peter D; Wang, Joseph R; Chan, Chun-Hao; Wei, Hong-Jian; Deng, Win-Ping

2018-05-31

NSC 95397, a quinone-based small molecule compound, has been identified as an inhibitor for dual-specificity phosphatases, including mitogen-activated protein kinase phosphatase-1 (MKP-1). MKP-1 is known to inactivate mitogen-activated protein kinases by dephosphorylating both of their threonine and tyrosine residues. Moreover, owing to their participation in tumorigenesis and drug resistance in colon cancer cells, MKP-1 is an attractive therapeutic target for colon cancer treatment. We therefore investigated the inhibitory activity of NSC 95397 against three colon cancer cell lines including SW480, SW620, and DLD-1, and their underlying mechanisms. The results demonstrated that NSC 95397 reduced cell viability and anchorage-independent growth of all the three colon cancer cell lines through inhibited proliferation and induced apoptosis via regulating cell-cycle-related proteins, including p21, cyclin-dependent kinases, and caspases. Besides, by using mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126, we provided mechanistic evidence that the antineoplastic effects of NSC 95397 were achieved via inhibiting MKP-1 activity followed by ERK1/2 phosphorylation. Conclusively, our results indicated that NSC 95397 might serve as an effective therapeutic intervention for colon cancer through regulating MKP-1 and ERK1/2 pathway.

Curcumin Regulates Colon Cancer by Inhibiting P-Glycoprotein in In-situ Cancerous Colon Perfusion Rat Model.

PubMed

Neerati, Prasad; Sudhakar, Yakkanti A; Kanwar, Jagat R

2013-07-08

Studies on p-glycoprotein was carried out world vide with cell lines like Caco2, MDR1-LLC-PK1 and MDR1-MDCK in-vitro , but most of the results were failed to produce similar results in-vivo. In the present study curcumin inhibitory action on p-glycoprotein increased permeability of irinotecan, so in the colon cancer it would be beneficial if curcumin used as add on therapy. Intra-rectal administered of N-Nitroso N-methyl urea (2 mg/Kg) induced colon cancer. Single pass whole length of colon in-situ perfusion was carried out in rats with irinotecan to study the influence of p-glycoprotein modulators like verapamil and curcumin. The rats were divided in to 5 groups (n=6), Group I served as control perfused with 30 μg/ml of irinotecan, propronolol and phenol red. Group II was cancerous group, induced by N-methyl N-nitroso urea. Group III was perfused with irinotican in cancerous rats. Group IV, perfused with irinotican in presence of verapamil and group V was pre-treated with curcumin and then perfused with irinotican and was estimated by HPLC-UV to effective permeability coefficient. Our qRT-PCR and Western blot results confirmed that about 15-fold decreases in the expression of p-glycoprotein (P-gp) in curcumin treated colon cancer cells. Irinotecan was increased to 0.00066 cm/s and about 11-fold increase in verapamil-coperfused group, where curcumin pre-treated group irinotecan was increases 0.00006 cm/s to 0.00042 cm/s that is about 7-fold increase p-glycoprotein inhibitory activity by verapamil and curcumin found to be significantly enhanced the cancerous colon permeability of irinotecan. Any safe suitable p-glycoprotein inhibitors along with irinotecan will enhance the therapeutic benefit in the treatment of the colon cancer.

The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation

PubMed Central

2011-01-01

Background This study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines. Methods Mice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 \\ groups (control, colitis, HFD and colitis + HFD). Results Obesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group. Conclusion Our results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream. PMID:22073943

Effect of Serotype on Pneumococcal Competition in a Mouse Colonization Model.

PubMed

Trzciński, Krzysztof; Li, Yuan; Weinberger, Daniel M; Thompson, Claudette M; Cordy, Derrick; Bessolo, Andrew; Malley, Richard; Lipsitch, Marc

2015-09-15

Competitive interactions between Streptococcus pneumoniae strains during host colonization could influence the serotype distribution in nasopharyngeal carriage and pneumococcal disease. We evaluated the competitive fitness of strains of serotypes 6B, 14, 19A, 19F, 23F, and 35B in a mouse model of multiserotype carriage. Isogenic variants were constructed using clinical strains as the capsule gene donors. Animals were intranasally inoculated with a mixture of up to six pneumococcal strains of different serotypes, with separate experiments involving either clinical isolates or isogenic capsule-switch variants of clinical strain TIGR4. Upper-respiratory-tract samples were repeatedly collected from animals in order to monitor changes in the serotype ratios using quantitative PCR. A reproducible hierarchy of capsular types developed in the airways of mice inoculated with multiple strains. Serotype ranks in this hierarchy were similar among pneumococcal strains of different genetic backgrounds in different strains of mice and were not altered when tested under a range of host conditions. This rank correlated with the measure of the metabolic cost of capsule synthesis and in vitro measure of pneumococcal cell surface charge, both parameters considered to be predictors of serotype-specific fitness in carriage. This study demonstrates the presence of a robust competitive hierarchy of pneumococcal serotypes in vivo that is driven mainly, but not exclusively, by the capsule itself. Streptococcus pneumoniae (pneumococcus) is the leading cause of death due to respiratory bacterial infections but also a commensal frequently carried in upper airways. Available vaccines induce immune responses against polysaccharides coating pneumococcal cells, but with over 90 different capsular types (serotypes) identified, they can only target strains of the selected few serotypes most prevalent in disease. Vaccines not only protect vaccinated individuals against disease but also protect by

Ursolic acid and oleanolic acid suppress preneoplastic lesions induced by 1,2-dimethylhydrazine in rat colon.

PubMed

Furtado, Ricardo A; Rodrigues, Erlon P; Araújo, Felipe R R; Oliveira, Wendel L; Furtado, Michelle A; Castro, Márcio B; Cunha, Wilson R; Tavares, Denise C

2008-06-01

Ursolic acid (UA) and oleanolic acid (OA) are pentacyclic triterpenoid compounds found in plants used in the human diet and in medicinal herbs, in the form of aglycones or as the free acid. These compounds are known for their hepatoprotective, anti-inflammatory, antimicrobial, hypoglycemic, antimutagenic, antioxidant, and antifertility activities. In the present study, we evaluated the effects of UA and OA on the formation of 1,2-dimethyl-hydrazine (DMH)-induced aberrant crypt foci (ACF) in the colon of the male Wistar rat. The animals received subcutaneous (sc) injections of DMH (40 mg/kg body weight) twice a week for two weeks to induce ACF. UA, OA and a mixture of UA and OA were administered to the rats five times a week for four weeks by gavage at doses of 25 mg/kg body weight/day each, during and after DMH treatment. All animals were sacrificed in week 5 for the evaluation of ACF. The results showed a significant reduction in the frequency of ACF in the group treated with the triterpenoid compounds plus DMH when compared to those treated with DMH alone, suggesting that UA and OA suppress the formation of ACF and have a protective effect against colon carcinogenesis.

Quantitative measurement of feline colonic transit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krevsky, B.; Somers, M.B.; Maurer, A.H.

1988-10-01

Colonic transit scintigraphy, a method for quantitatively evaluating the movement of the fecal stream in vivo, was employed to evaluate colonic transit in the cat. Scintigraphy was performed in duplicate in five cats and repeated four times in one cat. After instillation of an 111In marker into the cecum through a surgically implanted silicone cecostomy tube, colonic movement of the instillate was quantitated for 24 h using gamma scintigraphy. Antegrade and retrograde motion of radionuclide was observed. The cecum and ascending colon emptied rapidly, with a half-emptying time of 1.68 +/- 0.56 h (mean +/- SE). After 24 h, 25.1more » +/- 5.2% of the activity remained in the transverse colon. The progression of the geometric center was initially rapid, followed later by a delayed phase. Geometric center reproducibility was found to be high when analyzed using simple linear regression (slope = 0.92; r = 0.73; P less than 0.01). Atropine (0.1 mg/kg im) was found to delay cecum and ascending colon emptying and delay progression of the geometric center. These results demonstrate both 1) the ability of colonic transit scintigraphy to detect changes in transit induced by pharmacological manipulation and 2) the fact that muscarinic blockade inhibits antegrade transit of the fecal stream. We conclude that feline colonic transit may be studied in a quantitative and reproducible manner with colonic transit scintigraphy.« less

Photodynamic effects of pyropheophorbide-a methyl ester in nasopharyngeal carcinoma cells.

PubMed

Xu, Chuan Shan; Leung, Albert Wing Nang

2006-08-01

Nasopharyngeal carcinoma (NPC) is one of the most common cancers, and exploring novel therapeutic modalities will improve the clinical outcomes. It has been confirmed that photodynamic therapy can efficiently deactivate malignant cells. The aim of the present study was to explore the photodynamic effects of pyropheophorbide-a methyl ester (MPPa) in CNE2 nasopharyngeal carcinoma cells. CNE2 cells were subjected to photodynamic therapy with MPPa, in which the drug concentration was 0.25 to 4 microM and light energy 1 to 8 J/cm(2). Photodynamic toxicity was investigated 24 h after treatment. Apoptosis was determined using flow cytometry with annexin V-FITC and propidum iodine staining and with nuclear staining with Hoechst 33258. The mitochondrial membrane potential (DeltaPsim) was evaluated by Rhodamine 123 assay. There was no dark cytotoxicity of MPPa in the CNE2 cells at doses of 0.25-4 microM, and MPPa resulted in dose- and light-dependent phototoxicity. The apoptotic rate 8 h after PDT with MPPa (2 microM) increased to 16.43% under a light energy of 2 J/cm(2). Mitochondrial membrane potential (DeltaPsim) collapsed when the CNE2 cells were exposed to 2 microM MPPa for 20 h and then 2 J/cm(2) irradiation. Photodynamic therapy with MPPa significantly enhanced apoptosis and the collapse of DeltaPsim. This can be developed for treating nasopharyngeal carcinoma.

Ghrelin-induced stimulation of colonic propulsion is dependent on hypothalamic neuropeptide Y1- and corticotrophin-releasing factor 1 receptor activation.

PubMed

Tebbe, J J; Mronga, S; Tebbe, C G; Ortmann, E; Arnold, R; Schäfer, M K-H

2005-09-01

Peptides participating in the hypothalamic control of feeding behaviour are also involved in the central autonomic control of gastrointestinal functions, such as secretion and motility. An anatomical interaction and functional relationship in the central nervous system between the feeding-related peptides neuropeptide Y and ghrelin is well documented. Furthermore, it has been shown that feeding-related peptides can influence digestive function via central corticotrophin-releasing factor (CRF) pathways. In the present study, we investigated the role of ghrelin in the central autonomic control of colonic motility. Furthermore, we addressed the hypothesis that ghrelin is involved in the hypothalamic control of colonic motor function, utilizing central neuropeptide Y receptors and hypothalamic CRF pathways. Ghrelin (0.03, 0.06 and 0.12 nmol) bilaterally microinjected into the paraventricular nucleus (PVN) induced a significant stimulation of colonic propulsion. In particular, the colonic transit time decreased from 312+/-7 min to 198+/-12 min. Microinjection of the neuropeptide Y1 receptor antagonist, BIBP-3226 (200 pmol), or the nonselective CRF receptor antagonist, astressin (30 pmol), into the PVN abolished the stimulatory effect of ghrelin injected into the PVN on colonic transit time, whereas pretreatment with the selective CRF2 receptor, antisauvagine-30 (28 pmol), failed to affect the effect of PVN-ghrelin injection on colonic propulsion. These results suggest that ghrelin can act as central modulator of gastrointestinal motor functions at the level of the PVN via neuropeptide Y1- and CRF1 receptor-dependent mechanisms.

Sulforaphane Induces Cell Death Through G2/M Phase Arrest and Triggers Apoptosis in HCT 116 Human Colon Cancer Cells.

PubMed

Liu, Kuo-Ching; Shih, Ting-Ying; Kuo, Chao-Lin; Ma, Yi-Shih; Yang, Jiun-Long; Wu, Ping-Ping; Huang, Yi-Ping; Lai, Kuang-Chi; Chung, Jing-Gung

2016-01-01

Sulforaphane (SFN), an isothiocyanate, exists exclusively in cruciferous vegetables, and has been shown to possess potent antitumor and chemopreventive activity. However, there is no available information that shows SFN affecting human colon cancer HCT 116 cells. In the present study, we found that SFN induced cell morphological changes, which were photographed by contrast-phase microscopy, and decreased viability. SFN also induced G2/M phase arrest and cell apoptosis in HCT 116 cells, which were measured with flow cytometric assays. Western blotting indicated that SFN increased Cyclin A, cdk 2, Cyclin B and WEE1, but decreased Cdc 25C, cdk1 protein expressions that led to G2/M phase arrest. Apoptotic cell death was also confirmed by Annexin V/PI and DAPI staining and DNA gel electrophoresis in HCT 116 cells after exposure to SFN. The flow cytometric assay also showed that SFN induced the generation of reactive oxygen species (ROS) and Ca[Formula: see text] and decreased mitochondria membrane potential and increased caspase-8, -9 and -3 activities in HCT 116 cell. Western blotting also showed that SFN induced the release of cytochrome c, and AIF, which was confirmed by confocal microscopy examination. SFN induced ER stress-associated protein expression. Based on those observations, we suggest that SFN may be used as a novel anticancer agent for the treatment of human colon cancer in the future.

Carprofen-induced oxidative stress in mitochondria of the colonic mucosa of the dog.

PubMed

Snow, Lynne A; McConnico, Rebecca S; Morgan, Timothy W; Hartmann, Erica; Davidson, Jacqueline R; Hosgood, Giselle

2014-07-01

The purpose of the study was to compare the conductance and mannitol permeability of canine colonic mucosa in response to carprofen or 2,4-dinitrophenol (DNP) with or without tempol pretreatment. Ten colonic mucosa sections per dog were mounted in Ussing chambers. Treatments were done in duplicate. Mucosa was exposed to carprofen (200 μg/mL) or DNP (0.25 mM), both with and without tempol (1 mM) pretreatment. Conductance was calculated every 15 min for 240 min. Mannitol flux was calculated over 3 consecutive 60-minute periods. Histology or electron microscopy was done after exposure. Conductance over time, mannitol flux, frequency of histologic categories, and electron microscopic changes were analyzed for treatment effects. The mean ± standard deviation (SD) conductance over time for carprofen or DNP-treated colons was not significantly different from control regardless of tempol pretreatment. Period 3 mannitol fluxes for carprofen and DNP-treated colon were not significantly different, but were greater than control. Period 3 mannitol flux for tempol + carprofen was significantly less than tempol + DNP-treated colon. Sloughing of cells and erosions were seen in the mucosa of carprofen-treated colon. Mitochondrial damage was seen more often in carprofen-treated than DNP-treated or control colon. Tempol pretreatment resulted in more ruptured mitochondria in the carprofen-treated colon; however, other mitochondrial changes were not significantly affected by tempol pretreatment in either carprofen or DNP treated colon. Treatment with carprofen or DNP increased the mannitol flux, but pretreatment with tempol mitigated the carprofen effect. It is apparent that structural mitochondrial damage occurs in the canine colonic mucosa after carprofen and DNP exposure.

Carprofen-induced oxidative stress in mitochondria of the colonic mucosa of the dog

PubMed Central

Snow, Lynne A.; McConnico, Rebecca S.; Morgan, Timothy W.; Hartmann, Erica; Davidson, Jacqueline R.; Hosgood, Giselle

2014-01-01

The purpose of the study was to compare the conductance and mannitol permeability of canine colonic mucosa in response to carprofen or 2,4-dinitrophenol (DNP) with or without tempol pretreatment. Ten colonic mucosa sections per dog were mounted in Ussing chambers. Treatments were done in duplicate. Mucosa was exposed to carprofen (200 μg/mL) or DNP (0.25 mM), both with and without tempol (1 mM) pretreatment. Conductance was calculated every 15 min for 240 min. Mannitol flux was calculated over 3 consecutive 60-minute periods. Histology or electron microscopy was done after exposure. Conductance over time, mannitol flux, frequency of histologic categories, and electron microscopic changes were analyzed for treatment effects. The mean ± standard deviation (SD) conductance over time for carprofen or DNP-treated colons was not significantly different from control regardless of tempol pretreatment. Period 3 mannitol fluxes for carprofen and DNP-treated colon were not significantly different, but were greater than control. Period 3 mannitol flux for tempol + carprofen was significantly less than tempol + DNP-treated colon. Sloughing of cells and erosions were seen in the mucosa of carprofen-treated colon. Mitochondrial damage was seen more often in carprofen-treated than DNP-treated or control colon. Tempol pretreatment resulted in more ruptured mitochondria in the carprofen-treated colon; however, other mitochondrial changes were not significantly affected by tempol pretreatment in either carprofen or DNP treated colon. Treatment with carprofen or DNP increased the mannitol flux, but pretreatment with tempol mitigated the carprofen effect. It is apparent that structural mitochondrial damage occurs in the canine colonic mucosa after carprofen and DNP exposure. PMID:24982549

Effect of vanadium on colonic aberrant crypt foci induced in rats by 1,2 Dimethyl hydrazine

PubMed Central

Kanna, P Suresh; Mahendrakumar, CB; Chakraborty, T; Hemalatha, P; Banerjee, Pratik; Chatterjee, M

2003-01-01

AIM: To investigate the chemo preventive effects of vanadium on rat colorectal carcinogenesis induced by 1,2-dimethylhydrazine (DMH). METHODS: Male Sprague-Dawley Rats were randomly divided into four groups. Rats in Group A received saline vehicle alone for 16 weeks. Rats in Group B were given DMH injection once a week intraperitoneally for 16 weeks; rats in Group C, with the same DMH treatment as in the Group B, but received 0.5-ppm vanadium in the form ammonium monovanadate ad libitum in drinking water. Rats in the Group D received vanadium alone as in the Group C without DMH injection. RESULTS: Aberrant crypt foci (ACF) were formed in animals in DMH-treated groups at the end of week 16. Compared to DMH group, vanadium treated group had less ACF (P < 0.001). At the end of week 32, all rats in DMH group developed large intestinal tumors. Rats treated with vanadium contained significantly few colonic adenomas and carcinomas (P < 0.05) compared to rats administered DMH only. In addition, a significant reduction (P < 0.05) in colon tumor burden (sum of tumor sizes per animal) was also evident in animals of Group C when compared to those in rats of carcinogen control Group B. The results also showed that vanadium significantly lowered PCNA index in ACF (P < 0.005). Furthermore, vanadium supplementation also elevated liver GST and Cyt P-450 activities (P < 0.001 and P < 0.02, respectively). CONCLUSION: Vanadium in the form of ammonium monovanadate supplemented in drinking water ad libitum has been found to be highly effective in reducing tumor incidence and preneoplastic foci on DMH-induced colorectal carcinogenesis. These findings suggest that vanadium administration can suppress colon carcinogenesis in rats. PMID:12717849

Carbachol induces p70S6K1 activation through an ERK-dependent but Akt-independent pathway in human colonic epithelial cells.

PubMed

Jiang, Xiaohua; Sinnett-Smith, James; Rozengurt, Enrique

2009-09-25

Stimulation of human colonic epithelial T84 cells with the muscarinic receptor agonist carbachol, a stable analog of acetylcholine, induced Akt, p70S6K1 and ERK activation. Treatment of T84 cells with the selective inhibitor of EGF receptor (EGFR) tyrosine kinase AG1478 abrogated Akt phosphorylation on Ser(473) induced by either carbachol or EGF, indicating that carbachol-induced Akt activation is mediated through EGFR transactivation. Surprisingly, AG1478 did not suppress p70S6K1 phosphorylation on Thr(389) in response to carbachol, indicating the G protein-coupled receptor (GPCR) stimulation induces p70S6K1 activation, at least in part, via an Akt-independent pathway. In contrast, treatment with the selective MEK inhibitor U0126 (but not with the inactive analog U0124) inhibited carbachol-induced p70S6K1 activation, indicating that the MEK/ERK/RSK pathway plays a critical role in p70S6K1 activation in GPCR-stimulated T84 cells. These findings imply that GPCR activation induces p70S6K1 via ERK rather than through the canonical PI 3-kinase/Akt/TSC/mTORC1 pathway in T84 colon carcinoma cells.

Carbachol induces p70S6K1 activation through an ERK-dependent but Akt-independent pathway in human colonic epithelial cells

PubMed Central

Jiang, Xiaohua; Sinnett-Smith, James; Rozengurt, Enrique

2009-01-01

Stimulation of human colonic epithelial T84 cells with the muscarinic receptor agonist carbachol, a stable analog of acetylcholine, induced Akt, p70S6K1 and ERK activation. Treatment of T84 cells with the selective inhibitor of EGF receptor (EGFR) tyrosine kinase AG1478 abrogated Akt phosphorylation on Ser473 induced by either carbachol or EGF, indicating that carbachol-induced Akt activation is mediated through EGFR transactivation. Surprisingly, AG1478 did not suppress p70S6K1 phosphorylation on Thr389 in response to carbachol, indicating the G protein-coupled receptor (GPCR) stimulation induces p70S6K1 activation, at least in part, via an Akt-independent pathway. In contrast, treatment with the selective MEK inhibitor U0126 (but not with the inactive analog U0124) inhibited carbachol-induced p70S6K1 activation, indicating that the MEK/ERK/RSK pathway plays a critical role in p70S6K1 activation in GPCR-stimulated T84 cells. These findings imply that GPCR activation induces p70S6K1 via ERK rather than through the canonical PI 3-kinase/Akt/TSC/mTORC1 pathway in T84 colon carcinoma cells. PMID:19615971

The apoptotic effect of Zoledronic acid on the nasopharyngeal carcinoma cells via ROS mediated chloride channel activation.

PubMed

Wang, Liang; Gao, Hong; Yang, Xiaoya; Liang, Xiechou; Tan, Qiuchan; Chen, Zhanru; Zhao, Chan; Gu, Zhuoyu; Yu, Meisheng; Zheng, Yanfang; Huang, Yanqing; Zhu, Linyan; Jacob, Tim J C; Wang, Liwei; Chen, Lixin

2018-06-08

Zoledronic acid (ZA), a third-generation bisphosphonate, has been applied for treatment of bone metastases caused by malignant tumors. Recent studies have found its anti-cancer effects on various tumor cells. One of the mechanisms of anti-cancer effects of ZA is induction of apoptosis. However, the mechanisms of ZA-induced apoptosis in tumor cells have not been clarified clearly. In this study, we investigated the roles of chloride channels in ZA-induced apoptosis in nasopharyngeal carcinoma CNE-2Z cells. Apoptosis and chloride current were induced by ZA and suppressed by chloride channel blockers. After the knockdown of ClC-3 expression by ClC-3 siRNA, ZA-induced chloride current and apoptosis were significantly suppressed, indicating that the chloride channel participated in ZA-induced apoptosis may be ClC-3. When reactive oxygen species (ROS) generation was inhibited by the antioxidant N-acetyl-L-cysteine (L-NAC), ZA-induced apoptosis and chloride current were blocked accordingly, suggesting that ZA induces apoptosis through promoting ROS production and subsequently activating chloride channel. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Changing trends in the incidence of juvenile nasopharyngeal angiofibroma: seven decades of experience at King George's Medical University, Lucknow, India.

PubMed

Mishra, A; Mishra, S C

2016-04-01

The occurrence of juvenile nasopharyngeal angiofibroma is reportedly higher in India than in some other parts of the world, and our centre has seen a four-fold increase in its occurrence across seven decades. This paper reports a retrospective archival analysis of 701 juvenile nasopharyngeal angiofibroma cases from 1958 to 2013, and considers probable environmental factors in an Indian context that may affect its biology and the global distribution, as reported in the literature. A continuously progressive increase in occurrence was evident, but the rapid rise observed in the current decade was alarming. The world map of juvenile nasopharyngeal angiofibroma incidence does not reflect true global distribution given the paucity of reporting. Our centre has dealt with approximately 400 cases in the last 24 years. With the alarming increase in juvenile nasopharyngeal angiofibroma incidence, there is a need for a registry to define its epidemiology. The world literature needs to reflect the status of juvenile nasopharyngeal angiofibroma incidence in the third world as well. Environmental factors known for hormone disruptive actions may influence its occurrence. Such aspects need to be considered to plan specific prevention policies.

Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon.

PubMed

Jeon, Seong Gyu; Kayama, Hisako; Ueda, Yoshiyasu; Takahashi, Takuya; Asahara, Takashi; Tsuji, Hirokazu; Tsuji, Noriko M; Kiyono, Hiroshi; Ma, Ji Su; Kusu, Takashi; Okumura, Ryu; Hara, Hiromitsu; Yoshida, Hiroki; Yamamoto, Masahiro; Nomoto, Koji; Takeda, Kiyoshi

2012-01-01

Specific intestinal microbiota has been shown to induce Foxp3(+) regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103(+) dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103(+) DCs from Il10(-/-), Tlr2(-/-), and Myd88(-/-) mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103(+) DCs failed to induce IL-10 production from co-cultured Il27ra(-/-) T cells. B. breve treatment of Tlr2(-/-) mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103(+) DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4(+) T cells from wild-type mice, but not Il10(-/-) mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.

Apatinib has anti-tumor effects and induces autophagy in colon cancer cells.

PubMed

Lu, Wu; Ke, He; Qianshan, Ding; Zhen, Wang; Guoan, Xiang; Honggang, Yu

2017-09-01

Apatinib recently has been used to treat patients with gastric cancer, but the function of apatinib in colon cancer remains unclear. This study was conducted to investigate the impacts of apatinib on the biological function and its potential mechanism of colon cancer cells in vitro . The effect of apatinib in colon cancer cells were detected by assessing cell viability, migration and invasion capabilities. Apoptosis cells and the cell cycle distribution of colon cancer cells were analyzed by flow cytometry. The potential mechanism was investigated via autophagy related proteins and pathways in vitro . The proliferation, migration and invasion of colon cancer cells were inhibited when they were treated with different concentration of apatinib (20, 40 μM). When HCT116 and SW480 cells were treated with apatinib at the concentration of 20 μM, the apoptosis percentage were 3.7% and 5.8% respectively. As the drug concentration increased to 40μΜ, the the apoptosis percentage increased to 11.9% and 13.5%. Meanwhile, cell cycle was also altered. Furthermore, apatinib inhibited the expression of AKT-mTOR signaling pathway and increased the expression of LC3-II. Apatinib can significantly inhibit the malignant phenotype of colon cancer cells, and it was involved in regulation of autophagy.

Identification of nasopharyngeal carcinoma from photoluminescence spectra of 3C-SiC nanocrystals

NASA Astrophysics Data System (ADS)

Wang, Li-Fen; Guo, Jun-Hong; Huang, Zhi-Chun; Gu, Jian-Sen; Feng, Li-Ren; Liu, Li-Zhe

2017-09-01

The identification of intracellular pH (pHi) during carcinogenesis progression plays a crucial role in the studies of biochemistry, cytology, and clinical medicine. In this work, 3C-SiC nanocrystals (NCs), which can effectively monitor the pH environment by using the linear relation between photoluminescence intensity and surface OH- and H+ concentration, are adapted as fluorescent probes for monitoring carcinogenesis progression of nasopharyngeal carcinoma. Our results demonstrated that 3C-SiC NCs are compatible with living cells and have low cytotoxicity. The pHi measurements in different carcinogenesis environments indicate the validity and sensitivity of this technology in identifying nasopharyngeal carcinoma in application.

NoxO1 Controls Proliferation of Colon Epithelial Cells.

PubMed

Moll, Franziska; Walter, Maria; Rezende, Flávia; Helfinger, Valeska; Vasconez, Estefania; De Oliveira, Tiago; Greten, Florian R; Olesch, Catherine; Weigert, Andreas; Radeke, Heinfried H; Schröder, Katrin

2018-01-01

Reactive oxygen species (ROS) produced by enzymes of the NADPH oxidase family serve as second messengers for cellular signaling. Processes such as differentiation and proliferation are regulated by NADPH oxidases. In the intestine, due to the exceedingly fast and constant renewal of the epithelium both processes have to be highly controlled and balanced. Nox1 is the major NADPH oxidase expressed in the gut, and its function is regulated by cytosolic subunits such as NoxO1. We hypothesize that the NoxO1-controlled activity of Nox1 contributes to a proper epithelial homeostasis and renewal in the gut. NoxO1 is highly expressed in the colon. Knockout of NoxO1 reduces the production of superoxide in colon crypts and is not subsidized by an elevated expression of its homolog p47phox. Knockout of NoxO1 increases the proliferative capacity and prevents apoptosis of colon epithelial cells. In mouse models of dextran sulfate sodium (DSS)-induced colitis and azoxymethane/DSS induced colon cancer, NoxO1 has a protective role and may influence the population of natural killer cells. NoxO1 affects colon epithelium homeostasis and prevents inflammation.

XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells

PubMed Central

Ji, Jiao; Yu, Yan; Li, Zhi-Ling; Chen, Ming-Yuan; Deng, Rong; Huang, Xiang; Wang, Guang-Feng; Zhang, Meng-Xia; Yang, Qi; Ravichandran, Senthilkumar; Feng, Gong-Kan; Xu, Xue-Lian; Yang, Chen-Lu; Qiu, Miao-Zhen; Jiao, Lin; Yang, Dajun; Zhu, Xiao-Feng

2018-01-01

Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties. Here, we develop a novel CSC-targeting strategy to treat NPC through inhibiting IAPs. Methods: Human NPC S-18 and S-26 cell lines were used as the model system in vitro and in vivo. Fluorescence activated cell sorting (FACS) assay was used to detect nasopharyngeal SP cells and CD44+ cells. The characteristics of CSCs were defined by sphere suspension culture, colony formation assay and cell migration. The role of XIAP on the regulation of Sox2 protein stability and ERK1-mediated phosphorylation of Sox2 signaling pathway were analyzed using immunoblotting, immunoprecipitation, immunofluorescence, phosphorylation mass spectrometry, siRNA silencing and plasmid overexpression. The correlation between XIAP and Sox2 in NPC biopsies and their role in prognosis was performed by immunohistochemistry. APG-1387 or chemotherapies-induced cell death and apoptosis in S-18 and S-26 were determined by WST, immunoblotting and flow cytometry assay. Results: IAPs, especially X chromosome-linked IAP (XIAP), were elevated in CSCs of NPC, and these proteins were critically involved in the maintenance of CSCs properties by enhancing the stability of Sox2. Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non-CSCs. However, XIAP blocked autophagic degradation of Sox2 by inhibiting ERK1 activation in CSCs. Additionally, XIAP was positively correlated with Sox2

Novel aspects of cholinergic regulation of colonic ion transport

PubMed Central

Bader, Sandra; Diener, Martin

2015-01-01

Nicotinic receptors are not only expressed by excitable tissues, but have been identified in various epithelia. One aim of this study was to investigate the expression of nicotinic receptors and their involvement in the regulation of ion transport across colonic epithelium. Ussing chamber experiments with putative nicotinic agonists and antagonists were performed at rat colon combined with reverse transcription polymerase chain reaction (RT-PCR) detection of nicotinic receptor subunits within the epithelium. Dimethylphenylpiperazinium (DMPP) and nicotine induced a tetrodotoxin-resistant anion secretion leading to an increase in short-circuit current (Isc) across colonic mucosa. The response was suppressed by the nicotinic receptor antagonist hexamethonium. RT-PCR experiments revealed the expression of α2, α4, α5, α6, α7, α10, and β4 nicotinic receptor subunits in colonic epithelium. Choline, the product of acetylcholine hydrolysis, is known for its affinity to several nicotinic receptor subtypes. As a strong acetylcholinesterase activity was found in colonic epithelium, the effect of choline on Isc was examined. Choline induced a concentration-dependent, tetrodotoxin-resistant chloride secretion which was, however, resistant against hexamethonium, but was inhibited by atropine. Experiments with inhibitors of muscarinic M1 and M3 receptors revealed that choline-evoked secretion was mainly due to a stimulation of epithelial M3 receptors. Although choline proved to be only a partial agonist, it concentration-dependently desensitized the response to acetylcholine, suggesting that it might act as a modulator of cholinergically induced anion secretion. Thus the cholinergic regulation of colonic ion transport – up to now solely explained by cholinergic submucosal neurons stimulating epithelial muscarinic receptors – is more complex than previously assumed. PMID:26236483

Neural control of colonic cell proliferation.

PubMed

Tutton, P J; Barkla, D H

1980-03-15

The mitotic rate in rat colonic crypts and in dimethylhydrazine-induced colonic carcinomas was measured using a stathmokinetic technique. In sympathectomized animals cell proliferation was retarded in the crypts but not in the tumors, whereas in animals treated with Metaraminol, a drug which releases norepinephrine from nerve terminals, crypt cell but not tumor cell proliferation was accelerated. Blockade of alpha-adrenoceptors also inhibited crypt cell proliferation. However, stimulation of beta-adrenoceptors inhibited and blockade of beta-adrenoceptors accelerated tumor cell proliferation without influencing crypt cell proliferation. Injection of either serotonin or histamine stimulated tumor but not crypt cell proliferation and blockade or serotonin receptors or histamine H2-receptors inhibited tumor cell proliferation. It is postulated that cell proliferation in the colonic crypts, like that in the jejunal crypts, is under both endocrine and autonomic neural control whereas colonic tumor cell division is subject to endocrine regulation alone.

Inactivation of the CovR/S Virulence Regulator Impairs Infection in an Improved Murine Model of Streptococcus pyogenes Naso-Pharyngeal Infection

PubMed Central

Alam, Faraz M.; Turner, Claire E.; Smith, Ken; Wiles, Siouxsie; Sriskandan, Shiranee

2013-01-01

Streptococcus pyogenes is a leading cause of pharyngeal infection, with an estimated 616 million cases per year. The human nasopharynx represents the major reservoir for all S. pyogenes infection, including severe invasive disease. To investigate bacterial and host factors that influence S. pyogenes infection, we have devised an improved murine model of nasopharyngeal colonization, with an optimized dosing volume to avoid fulminant infections and a sensitive host strain. In addition we have utilized a refined technique for longitudinal monitoring of bacterial burden that is non-invasive thereby reducing the numbers of animals required. The model was used to demonstrate that the two component regulatory system, CovR/S, is required for optimum infection and transmission from the nasopharynx. There is a fitness cost conferred by covR/S mutation that is specific to the nasopharynx. This may explain why S. pyogenes with altered covR/S have not become prevalent in community infections despite possessing a selective advantage in invasive infection. PMID:23637876

The descriptive epidemiology of Streptococcus pneumoniae and Haemophilus influenzae nasopharyngeal carriage in children and adults in Kilifi District, Kenya

PubMed Central

Abdullahi, Osman; Nyiro, Joyce; Lewa, Pole; Slack, Mary; Scott, J. Anthony G.

2008-01-01

Background Transmission and nasopharyngeal colonization are necessary steps en route to invasive pneumococcal or Haemophilus influenzae disease but their patterns vary geographically. In East Africa we do not know how these pathogens are transmitted between population sub-groups nor which serotypes circulate commonly. Methods We did two cross-sectional nasopharyngeal swab surveys selecting subjects randomly from a population register to estimate prevalence and risk-factors for carriage in 2004. H. influenzae type b vaccine was introduced in 2001. Results Of 450 individuals sampled in the dry season, 414 were resampled during the rainy season. Among subjects 0-4, 5-9 and 10-85 years old pneumococcal carriage prevalence was 57%, 41% and 6.4%, respectively. H. influenzae prevalence was 26%, 24% and 3.0%, respectively. Prevalence of H. influenzae type b in children <5 years was 1.7%. Significant risk factors for pneumococcal carriage were rainy season (OR 1.65), coryza (OR 2.29) and co-culture of non-capsulate H. influenzae (OR 7.46). Coryza was also a risk factor for H. influenzae carriage (OR 1.90). Of 128 H. influenzae isolates 113 were non-capsulate. Among 279 isolates of Streptococcus pneumoniae 40 serotypes were represented and the distribution of serotypes varied significantly with age; 7-valent vaccine-types, vaccine-related types and non-vaccine types comprised 47%, 19% and 34% of strains from children aged <5 years. Among older persons they comprised 25%, 28% and 47%, respectively (p=0.005). Conclusions The study shows that pneumococcal carriage is common up to 9 years of age and that the majority of serotypes carried at all ages, are not covered specifically by the 7-valent pneumococcal conjugate vaccine. PMID:18162940

Nasopharyngeal Carriage of Streptococcus pneumoniae among Children in an Urban Setting in Brazil prior to PCV10 Introduction

PubMed Central

Menezes, Ana Paula de O.; Azevedo, Jailton; Leite, Mariela C.; Campos, Leila C.; Cunha, Marcelo; Carvalho, Maria da Gloria S.; Reis, Mitermayer G.; Ko, Albert I.; Weinberger, Daniel M.; Ribeiro, Guilherme; Reis, Joice N.

2015-01-01

Information on pneumococcal carriage in the pre-vaccine period is essential to predict and assess the impact of PCV in settings where disease surveillance is particularly difficult. Therefore, we present data on pneumococcal carriage before the introduction of the 10-valent-pneumococcal conjugate vaccine (PCV10) in Brazil. We conducted a prospective study on a cohort of 203 children aged < 5 years-old, randomly selected in an urban community located in the periphery of the city of Salvador, Brazil and followed them from January/2008 to January/2009. Nasopharyngeal swabs were collected from each child at four times. In total, 721 swabs were collected, yielding a pneumococcal carriage prevalence of 55% (n=398). In multivariate analyses, the variables associated with carriage were having contact with three or more children <2 years old (OR, 2.00; 95% CI 1.33–2.89) and living in a house with an average of 3 residents per room (OR, 1.77; 95% CI 1.05–3.10). Also, white participants were more likely to be protected from colonization (OR, 0.52; 95% CI 0.29–0.93), and prevalence of carriage varied over time, with lower prevalence occurring from February to June (OR, 0.53; 95% CI 0.37–0.78) compared to July to January. Contact with children under two years of age and living in crowded housing also were associated with colonization by highly invasive serotypes, although this relationship was not significant. The most prevalent vaccine serotypes were 6A/B (25.4%), 19F (10.1%) and 14 (9.0%), while the most prevalent non-vaccine serotypes were 16F (4.8%), 15B/C (4.5%) and 6C/D (3.5%). Overall, 38.4% (153/398) of the isolates were non-susceptible to penicillin, and of those, 73.8% (113/153) were non-susceptible to trimethoprim/sulfamethoxazole. Colonization rate by PCV10 serotypes was 52.2%. Routine PCV10 vaccination can lead to significant changes in pneumococcal serotypes found in NP colonization, indicating a need for continued monitoring, especially in crowded

Foci of aberrant crypts in the colons of mice and rats exposed to carcinogens associated with foods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tudek, B.; Bird, R.P.; Bruce, W.R.

1989-03-01

Aberrant crypt foci can be identified in the colons of rodents treated 3 wk earlier with azoxymethane, a known colon carcinogen. These crypts can easily be visualized in the unsectioned methylene blue-stained colons under light microscopy, where they are distinguished by their increased size, more prominent epithelial cells, and pericryptal space. They occur as single aberrant crypts or as two, three, or four aberrant crypts in a cluster. We compared the reported ability of carcinogens associated with the human diet to induce colon cancer with the measured rate of induction of aberrant crypts in female CF1 mice and Sprague-Dawley rats.more » The carcinogens used were 1,2-dimethylhydrazine, methyl nitrosourea, N-nitrosodimethylamine, benzo(a)pyrene, aflatoxin B1, 2-amino-6-methyldipyrido(1,2-alpha:3',2'-d)imidazole, 2-amino-3-methylimidazo(4,5-P)quinoline, 2-amino-3,4-dimethylimidazo(4,5-P)quinoline, and 3-amino-1-methyl-5H-pyrido(4,3-b)indole. Graded doses of these compounds were given to the animals by gavage twice with a 4-day interval, and the animals were terminated 3 wk later. All colon carcinogens induced aberrant crypts in a dose-related fashion. N-Nitrosodimethylamine and 3-amino-1-methyl-5H-pyrido(4,3-b)indole, carcinogenic compounds that do not induce colon cancer, did not induce them. The ability of the studied compounds to induce aberrant crypts was species specific; e.g., aflatoxin B1 and 2-amino-3,4-dimethylimidazo(4,5-P)quinoline induce about 20 times more in rats than mice. This relationship was consistent with their reported ability to induce colon cancer in these species. Results of the present study support the use of the aberrant crypt assays to screen colon-specific carcinogens and to study the process of colon carcinogenesis.« less

Chemopreventive efficacy of Andrographis paniculata on azoxymethane-induced aberrant colon crypt foci in vivo.

PubMed

Al-Henhena, Nawal; Ying, Rozaida Poh Yuen; Ismail, Salmah; Najm, Walaa; Najm, Wala; Khalifa, Shaden A M; El-Seedi, Hesham; Ameen Abdulla, Mahmood; Abdulla, Mahmood Ameen

2014-01-01

Andrographis paniculata is a grass-shaped medicinal herb, traditionally used in Southeast Asia. The aim of this study was to evaluate the chemoprotective effects of A. paniculata on colorectal cancer. A. paniculata ethanol extract was tested on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in vivo and in vitro. A. paniculata treated groups showed a significant reduction in the number of ACF of the treated rats. Microscopically, ACF showed remarkably elongated and stratified cells, and depletion of the submucosal glands of AOM group compared to the treated groups. Histologically, staining showed slightly elevated masses above the surrounding mucosa with oval or slit-like orifices. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) and β-catenin protein were down-regulated in the A. paniculata treated groups compared to the AOM group. When colon tissue was homogenized, malondialdehyde (MDA) and nitric oxide (NO) levels were significantly decreased, whereas superoxide dismutase (SOD) activity was increased in the treated groups compared to the AOM group. A. paniculata ethanol extract showed antioxidant and free radical scavenging activity, as elucidated by the measure of oxidative stress markers. Further, the active fractions were assessed against cell lines of CCD841 and HT29 colon cancer cells.

Ursodeoxycholic acid attenuates colonic epithelial secretory function

PubMed Central

Kelly, Orlaith B; Mroz, Magdalena S; Ward, Joseph B J; Colliva, Carolina; Scharl, Michael; Pellicciari, Roberto; Gilmer, John F; Fallon, Padraic G; Hofmann, Alan F; Roda, Aldo; Murray, Frank E; Keely, Stephen J

2013-01-01

Dihydroxy bile acids, such as chenodeoxycholic acid (CDCA), are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhoea associated with bile acid malabsorption. However, CDCA is rapidly metabolised by colonic bacteria to ursodeoxycholic acid (UDCA), the effects of which on epithelial transport are poorly characterised. Here, we investigated the role of UDCA in the regulation of colonic epithelial secretion. Cl− secretion was measured across voltage-clamped monolayers of T84 cells and muscle-stripped sections of mouse or human colon. Cell surface biotinylation was used to assess abundance/surface expression of transport proteins. Acute (15 min) treatment of T84 cells with bilateral UDCA attenuated Cl− secretory responses to the Ca2+ and cAMP-dependent secretagogues carbachol (CCh) and forskolin (FSK) to 14.0 ± 3.8 and 40.2 ± 7.4% of controls, respectively (n= 18, P < 0.001). Investigation of the molecular targets involved revealed that UDCA acts by inhibiting Na+/K+-ATPase activity and basolateral K+ channel currents, without altering their cell surface expression. In contrast, intraperitoneal administration of UDCA (25 mg kg−1) to mice enhanced agonist-induced colonic secretory responses, an effect we hypothesised to be due to bacterial metabolism of UDCA to lithocholic acid (LCA). Accordingly, LCA (50–200 μm) enhanced agonist-induced secretory responses in vitro and a metabolically stable UDCA analogue, 6α-methyl-UDCA, exerted anti-secretory actions in vitro and in vivo. In conclusion, UDCA exerts direct anti-secretory actions on colonic epithelial cells and metabolically stable derivatives of the bile acid may offer a new approach for treating intestinal diseases associated with diarrhoea. PMID:23507881

Magnolol inhibits colonic motility through down-regulation of voltage-sensitive L-type Ca2+ channels of colonic smooth muscle cells in rats.

PubMed

Zhang, Man; Zang, Kai-Hong; Luo, Jia-Lie; Leung, Fung-Ping; Huang, Yu; Lin, Cheng-Yuan; Yang, Zhi-Jun; Lu, Ai-Ping; Tang, Xu-Dong; Xu, Hong-Xi; Sung, Joseph Jao-yiu; Bian, Zhao-Xiang

2013-11-15

This study aimed to investigate the effect of magnolol (5,5'-diallyl-2,2'-biphenyldiol) on contraction in distal colonic segments of rats and the underlying mechanisms. Colonic segments were mounted in organ baths for isometric force measurement. Whole-cell voltage-sensitive L-type Ca(2+) currents were recorded on isolated single colonic smooth muscle cells using patch-clamp technique. The spontaneous contractions and acetylcholine (ACh)- and Bay K 8644-induced contractions were inhibited by magnolol (3-100 μM). In the presence of Bay K8644 (100 nM), magnolol (10-100 μM) inhibited the contraction induced by 10 μM ACh. By contrast, tetrodotoxin (100 nM) and Nώ-nitro-L-arginine methyl ester (L-NAME 100 μM) did not change the inhibitory effect of magnolol (10 μM). In addition, magnolol (3-100 μM) inhibited the L-type Ca(2+) currents. The present results suggest that magnolol inhibits colonic smooth muscle contraction through downregulating L-type Ca(2+) channel activity. Copyright © 2013 Elsevier GmbH. All rights reserved.

LZ-207, a Newly Synthesized Flavonoid, Induces Apoptosis and Suppresses Inflammation-Related Colon Cancer by Inhibiting the NF-κB Signaling Pathway.

PubMed

Sun, Jie; Li, Fanni; Zhao, Yue; Zhao, Li; Qiao, Chen; Li, Zhiyu; Guo, Qinglong; Lu, Na

2015-01-01

Flavonoids and flavonoid derivatives, which have significant biological and pharmacological activities, including antitumor and anti-inflammatory activities, have been widely used in human healthcare. To design a more effective flavonoid antitumor agent, we altered the flavonoid backbone with substitutions of piperazine and methoxy groups to synthesize a novel flavonoid derivative, LZ-207. The anticancer effect of LZ-207 against HCT116 colon cancer cells and the underlying mechanism of this effect were explored in this study. Specifically, LZ-207 exhibited inhibitory effects on growth and viability in several human colon cancer cell lines and induced apoptosis in HCT116 cells both in vitro and in vivo. LZ-207 treatment also suppressed the nuclear translocation of NF-κB and the phosphorylation of IκB and IKKα/β in a dose-dependent manner in both HCT116 cells and human acute monocytic leukemia THP-1 cells. Moreover, LZ-207 also reduced the secretion of the pro-inflammatory cytokine interleukin-6 (IL-6) in LPS-induced THP-1 cells, and this effect was confirmed at the transcriptional level. Furthermore, LZ-207 significantly inhibited HCT116 cell proliferation that was elicited by LPS-induced THP-1 cells in a co-culture system. These findings elucidated some potential molecular mechanisms for preventing inflammation-driven colon cancer using the newly synthesized flavonoid LZ-207 and suggested the possibility of further developing novel therapeutic agents derived from flavonoids.

Dimethoxy Curcumin Induces Apoptosis by Suppressing Survivin and Inhibits Invasion by Enhancing E-Cadherin in Colon Cancer Cells.

PubMed

Chen, Dong; Dai, Fang; Chen, Zhehang; Wang, Saisai; Cheng, Xiaobin; Sheng, Qinsong; Lin, Jianjiang; Chen, Wenbin

2016-09-11

BACKGROUND Dimethoxy curcumin (DMC) is a kind of lipophilic analog of curcumin with great improvement in chemical and metabolic stability. DMC has been studied in breast and renal cancer, but no research in colon cancer has been found yet. MATERIAL AND METHODS Two colon cancer cells (HT-29 and SW480) and one normal human colon mucosal epithelial cell (NCM460) were used in this study. We studied the effect of DMC on the proliferation in vitro and in vivo. Transwell migration assay was used to estimate the inhibition of DMC on invasion. Moreover, the expressions of PARP, caspase-3, survivin and E-cadherin were detected to uncover the related signaling pathways by western blotting assay both in vitro and in vivo. RESULTS DMC significantly inhibited the growth of colon cancer cells in dose-dependent manner; IC50 for DMC was calculated to be 43.4, 28.2 and 454.8µM on HT-29, SW480 and NCM460. DMC significantly increased the apoptosis in both HT-29 (p=0.0051) and SW480 (p=0.0013) cells in vitro, and significantly suppressed the growth of both cell lines in vivo. Moreover, DMC reduced the number of migrated cells in both HT-29 (p=0.007) and SW480 (p=0.004) cells. By western blotting analysis, the cleavage of pro-caspases-3 and PARP were clearly induced by DMC to their active form, while the expression of survivin was reduced and E-cadherin was enhanced in both cells in vitro and in vivo. CONCLUSIONS DMC may exert an effective anti-tumor effect in colon cancer cells by down-regulating survivin and upregulating E-cadherin.

Probiotic Bifidobacterium breve Induces IL-10-Producing Tr1 Cells in the Colon

PubMed Central

Ueda, Yoshiyasu; Takahashi, Takuya; Asahara, Takashi; Tsuji, Hirokazu; Tsuji, Noriko M.; Kiyono, Hiroshi; Ma, Ji Su; Kusu, Takashi; Okumura, Ryu; Hara, Hiromitsu; Yoshida, Hiroki; Yamamoto, Masahiro; Nomoto, Koji; Takeda, Kiyoshi

2012-01-01

Specific intestinal microbiota has been shown to induce Foxp3+ regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103+ dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103+ DCs from Il10 −/−, Tlr2 −/−, and Myd88 −/− mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103+ DCs failed to induce IL-10 production from co-cultured Il27ra −/− T cells. B. breve treatment of Tlr2 −/− mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103+ DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4+ T cells from wild-type mice, but not Il10 −/− mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells. PMID:22693446

The Effect of Ozone on Colonic Epithelial Cells.

PubMed

Himuro, Hidetomo

2018-05-21

Due to its strong oxidation activity, ozone has been well known to kill bacteria and exert toxic effects on human tissues. At the same time, ozone is being used for the treatment of diseases such as inflammatory bowel disease in some European countries. However, the use of ozone for therapeutic purposes, despite its strong toxic effects, remains largely unexplored. Interestingly, we found that intrarectal administration of ozone gas induced transient colonic epithelial cell damage characterized by the impairment of cell survival pathways involved in DNA replication, cell cycle, and mismatch repair. However, the damaged cells were rapidly extruded from the epithelial layer, and appeared to immediately stimulate turnover of the epithelial layer in the colon. Therefore, it is possible that ozone gas is able to trigger damage-induced rapid regeneration of intestinal epithelial cells, and that this explains why ozone does not cause harmful or persistent damage in the colon.

Colonic intussusception in descending colon: An unusual presentation of colon lipoma

PubMed Central

Bagherzadeh Saba, Reza; Sadeghi, Amir; Rad, Neda; Safari, Mohammad Taghi; Barzegar, Farnoush

2016-01-01

Lipomas of the colon are relatively rare benign soft tissue tumors derived from mature adipocytes of mesenchymatic origin. During colonoscopy, surgery or autopsy they are generally discovered incidentally. Most cases are asymptomatic, with a small tumor size, and do not need any special treatment. However, in the cases with larger in size of tumor some symptoms such as anemia, abdominal pain, constipation, diarrhea, bleeding, or intussusception may be presented. We reported a 47-year-old woman with colonic intussusception in the descending colon caused by colonic lipoma and diagnosed after surgical exploration for obstructive colonic mass. PMID:28224035

True bilateral nasopharyngeal angiofibroma: report and review.

PubMed

Mishra, Anupam; Mishra, Subhash Chandra

2016-10-01

This report describes the third case of a true bilateral Juvenile nasopharyngeal angiofibroma (JNA), i.e. two separate JNA arising from both sides simultaneously. The associated multiple recurrences in such a case have not yet been reported. A 21-year-man underwent transpalatal excision and recurred twice. The last 'neo-occurrence' encountered after 2 years was at a different site and was subsequently managed by post-embolization endoscopic resection. A complete report of its clinico-radiological features and management outcome is discussed.

Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion.

PubMed

Belo, Angelica; Cheng, Kunrong; Chahdi, Ahmed; Shant, Jasleen; Xie, Guofeng; Khurana, Sandeep; Raufman, Jean-Pierre

2011-05-01

Muscarinic receptors (CHRM) are overexpressed in colon cancer. To explore a role for muscarinic receptor signaling in colon cancer metastasis, we used human H508 and HT29 colon cancer cells that coexpress epidermal growth factor (ERBB) and CHRM3 receptors. In a wound closure model, following 8-h incubation of H508 cells with 100 μM ACh we observed a threefold increase in cell migration indistinguishable from the actions of epidermal growth factor (EGF). Atropine blocked the actions of ACh but not of EGF. In SNU-C4 colon cancer cells that express ERBB but not CHRM, EGF caused a threefold increase in migration; ACh had no effect. ACh-induced cell migration was attenuated by chemical inhibitors of ERBB1 activation, by anti-ERBB1 antibody, and by inhibitors of ERK and phosphatidylinositol 3-kinase (PI3K) signaling. Consistent with matrix metalloproteinase-7 (MMP7)-mediated release of an ERBB1 ligand, heparin binding epidermal growth factor-like growth factor (HBEGF), ACh-induced migration was inhibited by an MMP inhibitor and by anti-MMP7 and -HBEGF antibodies. ACh-induced cell migration was blocked by inhibiting RhoA and ROCK, key proteins that interact with the actin cytoskeleton. ACh-induced RhoA activation was attenuated by agents that inhibit ERBB1, ERK, and PI3K activation. Collectively, these findings indicate that ACh-induced cell migration is mediated by MMP7-mediated release of HBEGF, an ERBB ligand that activates ERBB1 and downstream ERK and PI3K signaling. In a cell invasion model, ACh-induced HT29 cell invasion was blocked by atropine. In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion.

Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion

PubMed Central

Belo, Angelica; Cheng, Kunrong; Chahdi, Ahmed; Shant, Jasleen; Xie, Guofeng; Khurana, Sandeep

2011-01-01

Muscarinic receptors (CHRM) are overexpressed in colon cancer. To explore a role for muscarinic receptor signaling in colon cancer metastasis, we used human H508 and HT29 colon cancer cells that coexpress epidermal growth factor (ERBB) and CHRM3 receptors. In a wound closure model, following 8-h incubation of H508 cells with 100 μM ACh we observed a threefold increase in cell migration indistinguishable from the actions of epidermal growth factor (EGF). Atropine blocked the actions of ACh but not of EGF. In SNU-C4 colon cancer cells that express ERBB but not CHRM, EGF caused a threefold increase in migration; ACh had no effect. ACh-induced cell migration was attenuated by chemical inhibitors of ERBB1 activation, by anti-ERBB1 antibody, and by inhibitors of ERK and phosphatidylinositol 3-kinase (PI3K) signaling. Consistent with matrix metalloproteinase-7 (MMP7)-mediated release of an ERBB1 ligand, heparin binding epidermal growth factor-like growth factor (HBEGF), ACh-induced migration was inhibited by an MMP inhibitor and by anti-MMP7 and -HBEGF antibodies. ACh-induced cell migration was blocked by inhibiting RhoA and ROCK, key proteins that interact with the actin cytoskeleton. ACh-induced RhoA activation was attenuated by agents that inhibit ERBB1, ERK, and PI3K activation. Collectively, these findings indicate that ACh-induced cell migration is mediated by MMP7-mediated release of HBEGF, an ERBB ligand that activates ERBB1 and downstream ERK and PI3K signaling. In a cell invasion model, ACh-induced HT29 cell invasion was blocked by atropine. In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion. PMID:21273532

Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells.

PubMed

Zou, Xue; Zhang, Mengxiao; Sun, Yiming; Zhao, Surong; Wei, Yingmei; Zhang, Xudong; Jiang, Chenchen; Liu, Hao

2015-10-01

Tumor cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, which is therefore targeted by therapeutic agents. The compound 3-bromopyruvate (3-BrPA), a strong alkylating agent and hexokinase inhibitor, inhibits tumor cell glycolysis and the production of ATP, causing apoptosis. 3-BrPA induces apoptosis of nasopharyngeal carcinoma (NPC) cell lines HNE1 and CNE-2Z, which may be related to its molecular mechanisms. In the present study, we investigated the effects of 3-BrPA on the viability, reactive oxygen species (ROS), apoptosis and other types of programmed cell death in NPC cells in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers.