Stable gastric pentadecapeptide BPC 157 heals rat colovesical fistula.

PubMed

Grgic, Tihomir; Grgic, Dora; Drmic, Domagoj; Sever, Anita Zenko; Petrovic, Igor; Sucic, Mario; Kokot, Antonio; Klicek, Robert; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

2016-06-05

To establish the effects of BPC 157 on the healing of rat colovesical fistulas, Wistar Albino male rats were randomly assigned to different groups. BPC 157, a stable gastric pentadecapeptide, has been used in clinical applications-specifically, in ulcerative colitis-and was successful in treating both external and internal fistulas. BPC 157 was provided daily, perorally, in drinking water (10µg/kg, 12ml/rat/day) until sacrifice or, alternatively, 10µg/kg or 10ng/kg intraperitoneally, with the first application at 30min after surgery and the last at 24h before sacrifice. Controls simultaneously received an equivolume of saline (5.0ml/kg ip) or water only (12ml/rat/day). Assessment (i.e., colon and vesical defects, fistula leaking, fecaluria and defecation through the fistula, adhesions and intestinal obstruction as healing processes) took place on days 7, 14 and 28. Control colovesical fistulas regularly exhibited poor healing, with both of the defects persisting; continuous fistula leakage; fecaluria and defecation through the fistula; advanced adhesion formation; and intestinal obstruction. By contrast, BPC 157 given perorally or intraperitoneally and in µg- and ng-regimens rapidly improved the whole presentation, with both colon and vesical defects simultaneously ameliorated and eventually healed. The maximal instilled volume was continuously raised until it reached the values of healthy rats, there were no signs of fecaluria and no defecation through the fistula, there was counteraction of advanced adhesion formation or there was an intestinal obstruction. In conclusion, BPC 157 effects appear to be suited to inducing full healing of colocutaneous fistulas in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Gastric pentadecapeptide BPC 157 as an effective therapy for muscle crush injury in the rat.

PubMed

Novinscak, Tomislav; Brcic, Luka; Staresinic, Mario; Jukic, Ivana; Radic, Bozo; Pevec, Danira; Mise, Sandro; Tomasovic, Sanja; Brcic, Iva; Banic, Tihomir; Jakir, Ana; Buljat, Gojko; Anic, Tomislav; Zoricic, Ivan; Romic, Zeljko; Seiwerth, Sven; Sikiric, Predrag

2008-01-01

Stable gastric pentadecapeptide BPC 157 accelerates the healing of a transected Achilles tendon and a transected quadriceps muscle. It may also be of clinical relevance as a systemic and local peptide treatment for crush injury of a major muscle, such as gastrocnemius muscle complex. BPC 157 is effective without a carrier, and it is presently undergoing trials for inflammatory bowel disease, and no toxicity has so far been reported. In crushed rats (force delivered 0.727 Ns/cm2), BPC 157 was applied either intraperitoneally or locally, as a thin cream layer, immediately after injury (sacrifice at 2 h), and once a day for 14 days. BPC 157 improved muscle healing, macroscopically (less hematoma and edema, no post-injury leg contracture), microscopically, functionally, and also based on enzyme activity (creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase). BPC 157, at all investigated intervals, given locally or intraperitoneally, accelerated post-injury muscle healing and also helped to restore the full function.

Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol drinking rats.

PubMed

Prkacin, I; Aralica, G; Perovic, D; Separovic, J; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Ziger, T; Anic, T; Sikiric, P; Seiwerth, S; Staresinic, M; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sjekavica, I; Sebecic, B; Boban-Blagaic, A; Ivasovic, Z

2001-01-01

Unlike severe gastric damage acutely induced by ethanol administration in rat, the ulcerogenic effect of chronic alcohol administration (3.03 g/kg b.w. or 7.28 g/kg b.w.) given in drinking water, producing liver lesions and portal hypertension, is far less investigated. Therefore, focus was on the antiulcer effect of the gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in variety of gastrointestinal lesions models (10 microg or 10 ng/kg b.w. i.p. or i.g.), ranitidine (10 mg/kg b.w. i.g.) and propranol (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). They were given once daily (1) throughout 10 days preceding alcohol consumption, (2) since beginning of alcohol drinking till the end of the study, (3) throughout the last month of alcohol consumption, 2 months after alcohol drinking had been initiated. Gastric lesions were assessed, at the end of 3 months drinking [(1), (2)] or with respect to therapeutic effect of medication before medication or at the end of therapy. Pentadecapeptide BPC 157, ranitidine and propranolol may prevent gastric lesion development if given prophylactically, before alcohol drinking. Likewise, they attenuate the lesion appearance given once daily throughout the drinking period. Importantly, when given therapeutically, they may antagonize otherwise pertinent lesion presence in stomach mucosa of the drinking rats. Thus, these results demonstrate that pentadecapeptide BPC 157, ranitidine and propranol may prevent, attenuate or reverse the gastric lesions appearance in chronically alcohol drinking rats, and may be used for further therapy, while the other studies showed that their effect (except to ranitidine) is parallel with their beneficial effect on liver lesion and portal hypertension.

Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats.

PubMed

Jandric, Ivan; Vrcic, Hrvoje; Jandric Balen, Marica; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Drmic, Domagoj; Seiwerth, Sven; Sikiric, Predrag

2013-03-12

Since an originally anti-ulcer stable gastric pentadecapeptide BPC 157 (PL 14736) was shown to promote healing of injured striated muscle and smooth muscle in the gastrointestinal tract, we explored its therapeutic potentials for leak point pressure (LPP) recovery in rat stress urinary incontinence (SUI) after transabdominal urethrolysis (TU) and prolonged vaginal dilatation (VD). During a 7-day period, TU-rats and VD-rats (or healthy rats) received BPC 157, either (i) intraperitoneally, 10 µg/kg or 10 ng/kg, once daily (first administration 30 min after surgery, last 24 h before LPP-testing and sacrifice), or (ii) per-orally, 10 µg/kg in drinking water (0.16 µg/mL, 12 mL/rat/day). Vesicourethral segments were harvested for immunohistochemical evaluation. All BPC 157 regimens counteracted decrease of LPP values in TU-rats and VD-rats. Additionally, BPC 157-TU rats (µg-intraperitoneally or per-orally) and BPC 157-VD rats (µg intraperitoneally) reached LPP values originally noted in healthy rats. Conversely, in healthy rats, BPC 157 did not alter LPP. Immunohistochemical studies revealed higher desmin (delineates striated organization of skeletal muscle), smooth muscle actin, and CD34 (angiogenic marker) positivity within the urethral wall in BPC 157-treated rats vs. controls, as well as overall preserved muscle/connective tissue ratio assessed with Mallory's trichrome staining. Pentadecapeptide BPC 157, applied parenterally or per-orally, appears to ameliorate the SUI in rat models, improving the otherwise detrimental course of healing after VD and TU, which may be analogous to human injury. These beneficial effects may possibly be selectively used in future strategies for treatment of SUI.

Over-dose insulin and stable gastric pentadecapeptide BPC 157. Attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, fatty liver, breakdown of liver glycogen, profound hypoglycemia and calcification in rats.

PubMed

Ilic, S; Brcic, I; Mester, M; Filipovic, M; Sever, M; Klicek, R; Barisic, I; Radic, B; Zoricic, Z; Bilic, V; Berkopic, L; Brcic, L; Kolenc, D; Romic, Z; Pazanin, L; Seiwerth, S; Sikiric, P

2009-12-01

We focused on over-dose insulin (250 IU/kg i.p.) induced gastric ulcers and then on other disturbances that were concomitantly induced in rats, seizures (eventually fatal), severely damaged neurons in cerebral cortex and hippocampus, hepatomegaly, fatty liver, increased AST, ALT and amylase serum values, breakdown of liver glycogen with profound hypoglycemia and calcification development. Calcium deposits were present in the blood vessel walls, hepatocytes surrounding blood vessels and sometimes even in parenchyma of the liver mainly as linear and only occasionally as granular accumulation. As an antidote after insulin, we applied the stable gastric pentadecapeptide BPC 157 (10 microg/kg) given (i) intraperitoneally or (ii) intragastrically immediately after insulin. Controls received simultaneously an equivolume of saline (5 ml/kg). Those rats that survived till the 180 minutes after over-dose application were further assessed. Interestingly, pentadecapeptide BPC 157, as an antiulcer peptide, may besides stomach ulcer consistently counteract all insulin disturbances and fatal outcome. BPC 157 rats showed no fatal outcome, they were mostly without hypoglycemic seizures with apparently higher blood glucose levels (glycogen was still present in hepatocytes), less liver pathology (i.e., normal liver weight, less fatty liver), decreased ALT, AST and amylase serum values, markedly less damaged neurons in brain and they only occasionally had small gastric lesions. BPC 157 rats exhibited mostly only dot-like calcium presentation. In conclusion, the success of BPC 157 therapy may indicate a likely role of BPC 157 in insulin controlling and BPC 157 may influence one or more causative process(es) after excessive insulin application.

Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats

PubMed Central

Jandric, Ivan; Vrcic, Hrvoje; Balen, Marica Jandric; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Drmic, Domagoj; Seiwerth, Sven; Sikiric, Predrag

2013-01-01

Background Since an originally anti-ulcer stable gastric pentadecapeptide BPC 157 (PL 14736) was shown to promote healing of injured striated muscle and smooth muscle in the gastrointestinal tract, we explored its therapeutic potentials for leak point pressure (LPP) recovery in rat stress urinary incontinence (SUI) after transabdominal urethrolysis (TU) and prolonged vaginal dilatation (VD). Material/Methods During a 7-day period, TU-rats and VD-rats (or healthy rats) received BPC 157, either (i) intraperitoneally, 10 μg/kg or 10 ng/kg, once daily (first administration 30 min after surgery, last 24 h before LPP-testing and sacrifice), or (ii) per-orally, 10 μg/kg in drinking water (0.16 μg/mL, 12 mL/rat/day). Vesicourethral segments were harvested for immunohistochemical evaluation. Results All BPC 157 regimens counteracted decrease of LPP values in TU-rats and VD-rats. Additionally, BPC 157-TU rats (μg-intraperitoneally or per-orally) and BPC 157-VD rats (μg intraperitoneally) reached LPP values originally noted in healthy rats. Conversely, in healthy rats, BPC 157 did not alter LPP. Immunohistochemical studies revealed higher desmin (delineates striated organization of skeletal muscle), smooth muscle actin, and CD34 (angiogenic marker) positivity within the urethral wall in BPC 157-treated rats vs. controls, as well as overall preserved muscle/connective tissue ratio assessed with Mallory’s trichrome staining. Conclusions Pentadecapeptide BPC 157, applied parenterally or per-orally, appears to ameliorate the SUI in rat models, improving the otherwise detrimental course of healing after VD and TU, which may be analogous to human injury. These beneficial effects may possibly be selectively used in future strategies for treatment of SUI. PMID:23478678

Stable gastric pentadecapeptide BPC 157 heals rectovaginal fistula in rats.

PubMed

Baric, Marko; Sever, Anita Zenko; Vuletic, Lovorka Batelja; Rasic, Zarko; Sever, Marko; Drmic, Domagoj; Pavelic-Turudic, Tatjana; Sucic, Mario; Vrcic, Hrvoje; Seiwerth, Sven; Sikiric, Predrag

2016-03-01

Rectovaginal fistula is a devastating condition providing more than 99% of patients for surgical treatment. We hypothesized that rectovaginal fistula may be healed by therapy with stable gastric pentadecapeptide BPC 157, in consistence with its initial clinical application and effect on external fistulas. BPC 157 (10μg/kg or 10ng/kg) was given perorally, in drinking water (0.16μg/ml or 0.16ng/ml, 12ml/rat/day) till sacrifice, or alternatively, intraperitoneally, first application at 30min after surgery, last at 24h before sacrifice. Controls simultaneously received an equivolume of saline (5.0ml/kg ip) or water only (12ml/rat/day). The assessment (i.e., rectal and vaginal defect, fistula leakage, defecation through the fistula, adhesions and intestinal obstruction as healing processes) was at day 1, 3, 5, 7, 10, 14 and 21. Regularly, rectovaginal fistulas exhibited poor healing, with both of the defects persisting, continuous fistula leakage, defecation through the fistula, advanced adhesion formation and intestinal obstruction. By contrast, BPC 157 given perorally or intraperitoneally, in μg- and ng-regimens rapidly improved the whole presentation, with both rectal and vaginal defects simultaneously ameliorated and eventually healed. The maximal instilled volume was continuously raised till the values of healthy rats were achieved, there were no signs of defecation through the fistula. A counteraction of advanced adhesion formation and intestinal obstruction was achieved. Microscopic improvement was along with macroscopic findings. BPC 157 effects appear to be suited to induce a full healing of rectovaginal fistulas in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Pentadecapeptide BPC 157 cream improves burn-wound healing and attenuates burn-gastric lesions in mice.

PubMed

Mikus, D; Sikiric, P; Seiwerth, S; Petricevic, A; Aralica, G; Druzijancic, N; Rucman, R; Petek, M; Pigac, B; Perovic, D; Kolombo, M; Kokic, N; Mikus, S; Duplancic, B; Fattorini, I; Turkovic, B; Rotkvic, I; Mise, S; Prkacin, I; Konjevoda, P; Stambuk, N; Anic, T

2001-12-01

The effects of the gastric pentadecapeptide BPC 157 were investigated when administered topically or systemically in burned mice. This agent is known to have a beneficial effect in a variety of models of gastrointestinal lesions, as well as on wound or fracture healing. Deep partial skin thickness burns (1.5x1.5 cm) covering 20% of total body area, were induced under anesthesia on the back of mice by controlled burning and gastric lesions were assessed 1, 2, 3, 7, 14 and 21 days following injury. The first application of BPC 157 was immediately following burning, and thereafter, once daily, until 24 h before sacrifice. In the initial experiments, exposure to direct flame for 5 s, the BPC 157 was applied at 10 microg or 10 ng/kg b.w. intraperitoneally (i.p.) by injection or alternatively, topically, at the burn, as a thin layer of cream (50 microg of BPC 157 dissolved in 2 ml of distilled water was mixed with 50 g of commercial neutral cream (also used as local vehicle-control)), while silver sulfadiazine 1% cream was a standard agent acting locally. Others received no local medication: they were treated i.p. by injection of distilled water (distilled water-control) or left without any medication (control). In subsequent experiments involving deeper burns (direct flame for 7 s), BPC 157 creams (50 microg, 5 microg, 500 ng, 50 ng or 5 ng of BPC 157 dissolved in 2 ml of distilled water was mixed with 50 g of commercial neutral cream), or vehicle as a thin layer of cream, were applied topically, at the burn. Compared with untreated controls, in both experiments, in the BPC 157 cream-treated mice all parameters of burn healing were improved throughout the experiment: less edema was observed and inflammatory cell numbers decreased. Less necrosis was seen with an increased number of capillaries along with an advanced formation of dermal reticulin and collagen fibers. An increased number of preserved follicles were observed. Two weeks after injury, BPC 157 cream

The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice.

PubMed

Blagaic, Alenka Boban; Blagaic, Vladimir; Romic, Zeljko; Sikiric, Predrag

2004-09-24

The stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W.1419), which was promising in inflammatory bowel disease (PL-10, PLD-116, PL-14736, Pliva) trials, protects against both acute and chronic alcohol-induced lesions in stomach and liver, but also, given peripherally, affects various centrally mediated disturbances. Now, in male NMRI mice BPC 157 (10 pg intraperitoneally, 10 ng and 10 microg, intraperitoneally or intragastrically) (i) strongly opposed acute alcohol (4 g/kg intraperitoneally) intoxication (i.e., quickly produced and sustained anesthesia, hypothermia, increased ethanol blood values, 25% fatality, 90-min assessment period) given before or after ethanol, and (ii) when given after abrupt cessation of ethanol (at 0 or 3 or 7 h withdrawal time), attenuated withdrawal (assessed through 24 hours) after 20%-alcohol drinking (7.6 g/kg) through 13 days, with provocation on the 14th day.

Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications.

PubMed

Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Kolenc, Danijela; Vuletic, Lovorka Batelja; Drmic, Domagoj; Grgic, Tihomir; Strbe, Sanja; Zukanovic, Goran; Crvenkovic, Dalibor; Madzarac, Goran; Rukavina, Iva; Sucic, Mario; Baric, Marko; Starcevic, Neven; Krstonijevic, Zoran; Bencic, Martina Lovric; Filipcic, Igor; Rokotov, Dinko Stancic; Vlainic, Josipa

2016-01-01

Brain-gut interaction involves, among others, peptidergic growth factors which are native in GI tract and have strong antiulcer potency and thus could from periphery beneficially affect CNS-disorders. We focused on the stable gastric pentadecapeptide BPC 157, an antiulcer peptidergic agent, safe in inflammatory bowel disease trials and now in multiple sclerosis trial, native and stable in human gastric juice. Review of our research on BPC 157 in terms of brain-gut axis. BPC 157 may serve as a novel mediator of Robert's cytoprotection, involved in maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was successful in the therapy of GI tract, periodontitis, liver and pancreas lesions, and in the healing of various tissues and wounds. Stimulated Egr-1 gene, NAB2, FAK-paxillin and JAK-2 pathways are hitherto implicated. Initially corresponding beneficial central influence was seen when BPC 157 was given peripherally and a serotonin release in particular brain areas, mostly nigrostriatal, was changed. BPC 157 modulates serotonergic and dopaminergic systems, beneficially affects various behavioral disturbances that otherwise appeared due to specifically (over)stimulated/damaged neurotransmitters systems. Besides, BPC 157 has neuroprotective effects: protects somatosensory neurons; peripheral nerve regeneration appearent after transection; after traumatic brain injury counteracts the otherwise progressing course, in rat spinal cord compression with tail paralysis, axonal and neuronal necrosis, demyelination, cyst formation and rescues tail function in both short-terms and long-terms; after NSAIDs or insulin overdose or cuprizone encephalopathies were attenuated along with GI, liver and vascular injuries. BPC 157, a gastric peptide, may serve as remedy in various CNS-disorders.

Pentadecapeptide BPC 157, cimetidine, ranitidine, bromocriptine, and atropine effect in cysteamine lesions in totally gastrectromized rats: a model for cytoprotective studies.

PubMed

Sikirić, P; Mikus, D; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Perić, J; Konjevoda, P; Perović, D; Jurina, L; Hanzevacki, M; Separović, J; Gjurasin, M; Jadrijević, S; Jelovac, N; Miklić, P; Buljat, G; Marović, A

1997-05-01

A superior effectiveness in various lesion assays was noted for the novel pentadecapeptide BPC 157, originated from human gastric juice protein (BPC) and claimed to be a cytoprotective agent. From this viewpoint, as a previously untreated experimental improvement to create an acid-free environmental for cytoprotection studies, total gastrectomy was done 24 hr before the ulcerogenic procedure. In the absence of stomach and gastric acid, the damaging effects of cysteamine (400 mg/kg subcutaneously, death 24 hr thereafter), to date thought to be an acid-related duodenal ulcerogen, and the BPC 157 cytoprotective effect (10 microg or 10 ng/kg intraperitoneally) were further challenged. BPC 157 was compared with reference agents [cimetidine (50), ranitidine (10), omeprazole (10), bromocriptine (10) and atropine (10) (mg/kg intraperitoneally, 1 hr before cysteamine] known to be also cytoprotective. In naive rats, with intact stomach, all of them showed a strong beneficial effect. Interestingly, in gastrectomized animals, the application of BPC 157 or the reference agents before cysteamine significantly prevented the otherwise severe duodenal lesion development noted in the control gastrectomized cysteamine rats. In groups without cysteamine, no lesions were noted (laparotomy, gastrectomy only, 24 or 48 hr postsurgical period), nor was lesion potentiation seen in cysteamine-treated laparotomized animals. In summary, these findings--equal damaging effect of cysteamine and equal protection of pentadecapeptide BPC 157 and reference agents in gastrectomized and rats with intact stomach--seem to be particularly relevant for a cytoprotective viewpoint. Without a stomach, the cysteamine damaging effect was convincingly defined as an essential gastric acid-independent injury (analogous to ethanol gastric lesions). Likewise, a high "cytoprotective capacity," apparently acid independent, common for all tested agents (novel pentadecapeptide BPC 157, cimetidine, ranitidine, omeprazole

Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation.

PubMed

Sebecić, B; Nikolić, V; Sikirić, P; Seiwerth, S; Sosa, T; Patrlj, L; Grabarević, Z; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Perović, D; Slaj, M

1999-03-01

Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also

Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications

PubMed Central

Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Kolenc, Danijela; Vuletic, Lovorka Batelja; Drmic, Domagoj; Grgic, Tihomir; Strbe, Sanja; Zukanovic, Goran; Crvenkovic, Dalibor; Madzarac, Goran; Rukavina, Iva; Sucic, Mario; Baric, Marko; Starcevic, Neven; Krstonijevic, Zoran; Bencic, Martina Lovric; Filipcic, Igor; Rokotov, Dinko Stancic; Vlainic, Josipa

2016-01-01

Background Brain-gut interaction involves, among others, peptidergic growth factors which are native in GI tract and have strong antiulcer potency and thus could from periphery beneficially affect CNS-disorders. We focused on the stable gastric pentadecapeptide BPC 157, an antiulcer peptidergic agent, safe in inflammatory bowel disease trials and now in multiple sclerosis trial, native and stable in human gastric juice. Methods Review of our research on BPC 157 in terms of brain-gut axis. Results BPC 157 may serve as a novel mediator of Robert’s cytoprotection, involved in maintaining of GI mucosa integrity, with no toxic effect. BPC 157 was successful in the therapy of GI tract, periodontitis, liver and pancreas lesions, and in the healing of various tissues and wounds. Stimulated Egr-1 gene, NAB2, FAK-paxillin and JAK-2 pathways are hitherto implicated. Initially corresponding beneficial central influence was seen when BPC 157 was given peripherally and a serotonin release in particular brain areas, mostly nigrostriatal, was changed. BPC 157 modulates serotonergic and dopaminergic systems, beneficially affects various behavioral disturbances that otherwise appeared due to specifically (over)stimulated/damaged neurotransmitters systems. Besides, BPC 157 has neuroprotective effects: protects somatosensory neurons; peripheral nerve regeneration appearent after transection; after traumatic brain injury counteracts the otherwise progressing course, in rat spinal cord compression with tail paralysis, axonal and neuronal necrosis, demyelination, cyst formation and rescues tail function in both short-terms and long-terms; after NSAIDs or insulin overdose or cuprizone encephalopathies were attenuated along with GI, liver and vascular injuries. Conclusion BPC 157, a gastric peptide, may serve as remedy in various CNS-disorders. PMID:27138887

A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidol-induced supersensitivity to amphetamine.

PubMed

Jelovac, N; Sikirić, P; Rucman, R; Petek, M; Perović, D; Konjevoda, P; Marović, A; Seiwerth, S; Grabarević, Z; Sumajstorcić, J; Dodig, G; Perić, J

1998-04-01

A novel gastric pentadecapeptide, BPC 157, has been shown to attenuate different lesions (i.e., gastrointestinal tract, liver, pancreas, somatosensory neurons). This suggests an interaction with the dopamine system. When used alone, BPC 157 does not affect gross behavior or induce stereotypy. We first investigated the effect of pentadecapeptide BPC 157 on stereotypy and acoustic startle response in rats, given as either a prophylactic (10 micrograms/kg i.p.) or therapeutic (10 ng/kg i.p.) regimen, with the dopamine indirect agonist amphetamine (10 mg/kg i.p.). There was a marked attenuation of stereotypic behavior and acoustic startle response. When the medication was given at the time of maximum amphetamine-induced excitability, there was a reversal of this behavior. A further focus was on the effect of this pentadecapeptide on increased climbing behavior in mice pretreated with the dopamine antagonist haloperidol (5.0 mg/kg i.p.), and subsequently treated with amphetamine (20 mg/kg i.p. challenge 1, 2, 4, and 10 days after haloperidol pretreatment). This protocol is usually used for the study of behavioral supersensitivity to the amphetamine stimulating effect. An almost complete reversal was noted when pentadecapeptide was coadministered with haloperidol. Together, these data provide compelling evidence for the interaction of pentadecapeptide BPC 157 with the dopamine system.

Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response.

PubMed

Sikiric, P; Seiwerth, S; Brcic, L; Blagaic, A B; Zoricic, I; Sever, M; Klicek, R; Radic, B; Keller, N; Sipos, K; Jakir, A; Udovicic, M; Tonkic, A; Kokic, N; Turkovic, B; Mise, S; Anic, T

2006-12-01

Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, safe in clinical trials for inflammatory bowel disease (PL 10, PLD 116, PLD 14736, Pliva, Croatia)) has a particular cytoprotective/adaptive cytoprotective activity. The cytoprotective/adaptive cytoprotection researches largely neglect that stomach distension could per se jeopardize the mucosal integrity, with constantly stretched mucosa and blood vessels, and sphincters more prone for reflux induction. After absolute alcohol instillation in fully distended rat stomach, gastric, esophageal and duodenal lesions occur. Throughout next 3 min, left gastric artery blood vessels clearly disappear at the serosal site, indicative for loss of vessels both integrity and function. Contrary, constant vessels presentation could predict the beneficial effect of applied agent. After pentadecapeptide BPC 157 instillation into the stomach the vessels presentation remains constant, and lesions of stomach, esophagus, and duodenum are inhibited. Standards (atropine, ranitidine, omeprazole) could only slightly improve the vessels presentation compared to control values, and they have only a partial effect on the lesions. In this review we emphasize BPC 157 unusual stability, and some of its important effects: effectiveness against various lesions in gastrointestinal tract, on nitric oxide (NO)-system, and NO-agents effects, on somatosensory neurons, salivary glands function, recovery of AMP-ADP-ATP system, endothelium protection, effect on endothelin, and on angiogenesis promotion. It also antagonizes other alcohol effects, including acute and chronic intoxication. Given peripherally, it counteracts the consequence of central dopamine system disturbances (receptor blockade), and induces serotonin release in substantia nigra. Therapeutic potential of BPC 157 as a cytoprotective agent is also seen in its capability to heal various wounds. Given directly into the stomach, BPC 157 instantly recovers disturbed lower esophageal

Modulatory effect of gastric pentadecapeptide BPC 157 on angiogenesis in muscle and tendon healing.

PubMed

Brcic, L; Brcic, I; Staresinic, M; Novinscak, T; Sikiric, P; Seiwerth, S

2009-12-01

Angiogenesis is a natural and complex process controlled by angiogenic and angiostatic molecules, with a central role in healing process. One of the most important modulating factors in angiogenesis is the vascular endothelial growth factor (VEGF). Pentadecapeptide BPC 157 promotes healing demonstrating particular angiogenic/angiomodulatory potential. We correlated the angiogenic effect of BPC 157 with VEGF expression using in vitro (cell culture) and in vivo (crushed muscle and transected muscle and tendon) models. Results revealed that there is no direct angiogenic effect of BPC 157 on cell cultures. On the other hand, immunohistochemical analysis of muscle and tendon healing using VEGF, CD34 and FVIII antibodies showed adequately modulated angiogenesis in BPC 157 treated animals, resulting in a more adequate healing. Therefore the angiogenic potential of BPC 157 seems to be closely related to the healing process in vivo with BPC 157 stimulating angiogenesis by up-regulating VEGF expression.

The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. The effect of N(G)-nitro-L-arginine methyl ester and L-arginine.

PubMed

Boban-Blagaic, Alenka; Blagaic, Vladimir; Romic, Zeljko; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Seiwerth, Sven; Sikiric, Predrag

2006-01-01

Alcohol disturbances, NO stimulation (by the NO-precursor L-arginine), and/or NO-synthesis blockade (by N(G)-nitro-L-arginine methyl ester, i.e. L-NAME) were challenged with stable gastric pentadecapeptide BPC 157, which inhibits both acute alcohol intoxication and alcohol withdrawal symptoms. Mice received intraperitoneally (i.p.) BPC 157 (10 microg/kg), L-NAME (10 mg/kg), and L-arginine (400 mg/kg), alone or in combination, 5 minutes before or after acute ethanol (4 g/kg i.p.) intoxication or after 0, 3, or 7 hours of withdrawal after drinking 20% alcohol for 13 days. BPC 157 rapidly opposes the strongest disturbance presentations in acute intoxication (sustained ethanol anesthesia, complete loss of righting reflex, no reaction to external stimuli, hypothermia, 25% mortality) and withdrawal (prominent seizures). NO-agents: Aggravation of acute alcohol intoxication and opposition to withdrawal are common, but the later intervals affected by L-arginine and the action throughout the experiment by L-NAME are distinctive. Given together, L-arginine and L-NAME counteract each other, while either the "L-NAME presentation" (acute intoxication) or the "L-arginine presentation" (withdrawal) predominates. BPC157+NO-agent: In acute intoxication (L-NAME predominating in NO-system functioning to aggravate intoxication), both BPC157+L-NAME and BPC157+L-arginine follow the presentation of L-NAME, but without worsened mortality. In withdrawal (L-arginine predominating in NO-system functioning to oppose disturbance symptoms), BPC157+L-NAME follows the presentation of L-NAME, while BPC 157+L-arginine imitates that of L-arginine. The relationships among pentadecapeptide BPC 157, the NO-system, acute alcohol intoxication, and opposed withdrawal may be important, presenting pentadecapeptide BPC 157 as a suitable alcohol antagonist.

Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157.

PubMed

Staresinic, Mario; Petrovic, Igor; Novinscak, Tomislav; Jukic, Ivana; Pevec, Damira; Suknaic, Slaven; Kokic, Neven; Batelja, Lovorka; Brcic, Luka; Boban-Blagaic, Alenka; Zoric, Zdenka; Ivanovic, Domagoj; Ajduk, Marko; Sebecic, Bozidar; Patrlj, Leonardo; Sosa, Tomislav; Buljat, Gojko; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

2006-05-01

We report complete transection of major muscle and the systemic peptide treatment that induces healing of quadriceps muscle promptly and then maintains the healing with functional restoration. Initially, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736 Pliva, Croatia; in trials for inflammatory bowel disease; wound treatment; no toxicity reported; effective alone without carrier) also superiorly accelerates the healing of transected Achilles tendon. Regularly, quadriceps muscle completely transected transversely 1.0 cm proximal to patella presents a definitive defect that cannot be compensated in rat. BPC 157 (10 microg, 10 ng, 10 pg/kg) is given intraperitoneally, once daily; the first application 30 min posttransection, the final 24 h before sacrifice. It consistently improves muscle healing throughout the whole 72-day period. Improved are: (i) biomechanic (load of failure increased); (ii) function (walking recovery and extensor postural thrust/motor function index returned toward normal healthy values); (iii) microscopy/immunochemistry [i.e., mostly muscle fibers connect muscle segments; absent gap; significant desmin positivity for ongoing regeneration of muscle; larger myofibril diameters on both sides, distal and proximal (normal healthy rat-values reached)]; (iv) macroscopic presentation (stumps connected; subsequently, atrophy markedly attenuated; finally, presentation close to normal noninjured muscle, no postsurgery leg contracture). Thus, posttransection healing-consistently improved-may suggest this peptide therapeutic application in muscle disorders. Copyright 2006 Orthopaedic Research Society.

Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress, ethanol, indomethacin, and capsaicin neurotoxicity.

PubMed

Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Gjurasin, M; Konjevoda, P; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Jurina, L; Buljat, G; Miklić, P; Marović, A

1996-08-01

Very recently, the integrity of capsaicin somatosensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions. Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvement of sensory neurons in the salutary actions of BPC 157 (10 micrograms/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500 micrograms/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157. However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well. Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity.

Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: Promoted tendon-to-bone healing and opposed corticosteroid aggravation.

PubMed

Krivic, Andrija; Anic, Tomislav; Seiwerth, Sven; Huljev, Dubravko; Sikiric, Predrag

2006-05-01

Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no toxicity reported) alone (without carrier) ameliorates healing of tendon and bone, respectively, as well as other tissues. Thereby, we focus on Achilles tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it was recovered by this peptide. After the rat's Achilles tendon was sharply transected from calcaneal bone, agents [BPC 157 (10 microg, 10 ng, 10 pg), 6alpha-methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after Achilles detachment, BPC 157 improves healing functionally [Achilles functional index (AFI) values substantially increased], biomechanically (load to failure, stiffness, and Young elasticity modulus significantly increased), macro/microscopically, immunohistochemistry (better organization of collagen fibers, and advanced vascular appearance, more collagen type I). 6alpha-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6alpha-methylprednisolone healing aggravation. Thus, direct tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier might successfully exchange the present reconstructive surgical methods. Copyright 2006 Orthopaedic Research Society.

Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights.

PubMed

Duzel, Antonija; Vlainic, Josipa; Antunovic, Marko; Malekinusic, Dominik; Vrdoljak, Borna; Samara, Mariam; Gojkovic, Slaven; Krezic, Ivan; Vidovic, Tinka; Bilic, Zdenko; Knezevic, Mario; Sever, Marko; Lojo, Nermin; Kokot, Antonio; Kolovrat, Marijan; Drmic, Domagoj; Vukojevic, Jaksa; Kralj, Tamara; Kasnik, Katarina; Siroglavic, Marko; Seiwerth, Sven; Sikiric, Predrag

2017-12-28

To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. Medication [BPC 157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived colon segment. During reperfusion, medication was BPC 157 or saline. We recorded (USB microscope camera) vessel presentation through next 15 min of ischemic colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC-rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157 bath. Commonly, in colon segment (25 mm, 2 ligations on left colic artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC + OB-rats, BPC 157 (10 μg/kg) bath (1 mL/rat) increased vessel presentation, inside/outside arcade interconnections quickly reappeared, mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg). MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects; the treated colon segment was of normal diameter, and only small adhesions were present. BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system.

Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights

PubMed Central

Duzel, Antonija; Vlainic, Josipa; Antunovic, Marko; Malekinusic, Dominik; Vrdoljak, Borna; Samara, Mariam; Gojkovic, Slaven; Krezic, Ivan; Vidovic, Tinka; Bilic, Zdenko; Knezevic, Mario; Sever, Marko; Lojo, Nermin; Kokot, Antonio; Kolovrat, Marijan; Drmic, Domagoj; Vukojevic, Jaksa; Kralj, Tamara; Kasnik, Katarina; Siroglavic, Marko; Seiwerth, Sven; Sikiric, Predrag

2017-01-01

AIM To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. METHODS Medication [BPC 157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived colon segment. During reperfusion, medication was BPC 157 or saline. We recorded (USB microscope camera) vessel presentation through next 15 min of ischemic colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC-rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157 bath. RESULTS Commonly, in colon segment (25 mm, 2 ligations on left colic artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC + OB-rats, BPC 157 (10 μg/kg) bath (1 mL/rat) increased vessel presentation, inside/outside arcade interconnections quickly reappeared, mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg). MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects; the treated colon segment was of normal diameter, and only small adhesions were present. CONCLUSION BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system. PMID:29358856

Perforating corneal injury in rat and pentadecapeptide BPC 157.

PubMed

Masnec, Sanja; Kokot, Antonio; Zlatar, Mirna; Kalauz, Miro; Kunjko, Kristian; Radic, Bozo; Klicek, Robert; Drmic, Domagoj; Lazic, Ratimir; Brcic, Luka; Radic, Radivoje; Ivekovic, Renata; Seiwerth, Sven; Sikiric, Predrag

2015-07-01

Based on its healing effects in various tissues, we hypothesized that the stable gastric pentadecapeptide BPC 157 heals corneal ulcerations in rats and effects corneal transparency. We made a penetrant linear 2-mm incision in the paralimbal region of the left cornea at the 5 o'clock position with a 20-gauge MVR incision knife at 45° under an operating microscope. Medication was BPC 157 (2 pg/mL, 2 ng/mL, and 2 μg/mL distilled water, two eye drops/left rat eye) immediately after injury induction and then every 8 h up to 120 h; controls received an equal volume of distilled water. In contrast to the poor healing response in controls, BPC 157 significantly accelerated the healing process in 2 μg and 2 ng BPC 157-treated eyes, starting 24 h after the injury, and the fluorescein and Seidel tests became negative. The epithelial defects were completely healed at 72 h (2 μg BPC 157-treated group) and at 96 h (2 ng BPC 157-treated group) after injury. Aqueous cells were absent at 96 h and 120 h after injury in the 2 μg and 2 ng BPC 157-treated groups, respectively. In conclusion, BPC 157 effects the rapid regaining of corneal transparency. Whereas controls developed new vessels that grew from the limbus to the penetrated area, BPC 157-treated rats generally had no new vessels, and those that did form in the limbus did not make contact with the penetrated area. Thus, BPC 157 eye drops successfully close perforating corneal incisions in rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts.

PubMed

Chang, Chung-Hsun; Tsai, Wen-Chung; Hsu, Ya-Hui; Pang, Jong-Hwei Su

2014-11-19

BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed to explore the effect of BPC 157 on tendon fibroblasts isolated from Achilles tendon of male Sprague-Dawley rat. From the result of cDNA microarray analysis, growth hormone receptor was revealed as one of the most abundantly up-regulated genes in tendon fibroblasts by BPC 157. BPC 157 dose- and time-dependently increased the expression of growth hormone receptor in tendon fibroblasts at both the mRNA and protein levels as measured by RT/real-time PCR and Western blot, respectively. The addition of growth hormone to BPC 157-treated tendon fibroblasts dose- and time-dependently increased the cell proliferation as determined by MTT assay and PCNA expression by RT/real-time PCR. Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. In conclusion, the BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormone and contribute to the healing of tendon.

Pentadecapeptide BPC 157 and the esophagocutaneous fistula healing therapy.

PubMed

Cesarec, Vedran; Becejac, Tomislav; Misic, Marija; Djakovic, Zeljko; Olujic, Danijela; Drmic, Domagoj; Brcic, Luka; Rokotov, Dinko Stancic; Seiwerth, Sven; Sikiric, Predrag

2013-02-15

Esophagocutaneous fistulas are a failure of the NO-system, due to NO-synthase blockage by the NOS-blocker L-NAME consequently counteracted by l-arginine and gastric pentadecapeptide BPC 157 (l-arginine <BPC 157), precipitating a therapeutic benefit. Previously, there was an established BPC 157-NO-system interaction. BPC 157 GEPPPGKPADDAGLV, MW 1419 (LD1 not achieved), is a safe and stable anti-ulcer peptide, successful in inflammatory bowel disease trials, counteracting esophagitis, sphincter failure, gastrointestinal and skin ulcers, gastrocutaneous or colocutaneous fistulas. We treated rats with established cervical esophagocutaneous fistulas throughout four days (both open skin and esophageal defects, with significant leakage) with BPC 157 (parenterally and perorally) and L-NAME (blocking NO genesis) and l-arginine (NO-substrate) alone or in combination. RT-PCR investigated eNOS, iNOS, COX-2 mRNA levels in the fistulas. We evidenced a closely inter-related process of unhealed skin, esophageal defects, unhealed fistulas (up regulated eNOS, iNOS and COX2 mRNA levels), usually lethal, particularly NO-system related and therapy dependent. Generally, the course of fistula healing was accelerated either to a greater extent (with BPC 157 (in particular, less eNOS gene expression) completely counteracting L-NAME effects, in L-NAME+BPC 157 and L-NAME+l-arginine+BPC 157 groups), or to a lesser extent (with l-arginine). Conversely, the process was aggravated, rapidly and prominently (with L-NAME). In particular, BPC 157 was effective either given per-orally/intraperitoneally, in μg- and ng-regimens. Shortly, defects started to heal, with less fistula leakage and no mortality at day 4. Failure of pyloric and lower esophageal sphincter pressure was restored, with practically no esophagitis. Copyright © 2012 Elsevier B.V. All rights reserved.

Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat.

PubMed

Cerovecki, Tomislav; Bojanic, Ivan; Brcic, Luka; Radic, Bozo; Vukoja, Ivan; Seiwerth, Sven; Sikiric, Predrag

2010-09-01

We improved medial collateral ligament (MCL) healing throughout 90 days after surgical transection. We introduced intraperitoneal, per-oral (in drinking water) and topical (thin cream layer) peptide therapy always given alone, without a carrier. Previously, as an effective peptide therapy, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide effective in inflammatory bowel disease therapy (PL 14736)) particularly improved healing of transected tendon and muscle and wound healing effect including the expression of the early growth response 1 (egr-1) gene. After MCL transection BPC 157 was effective in rats when given once daily intraperitoneally (10 microg or 10 ng/kg) or locally as a thin layer (1.0 microg dissolved in distilled water/g commercial neutral cream) at the site of injury, first application 30 min after surgery and the final application 24 h before sacrifice. Likewise, BPC 157 was effective given per-orally (0.16 microg/ml in the drinking water (12 ml/day/rat)) until sacrifice. Commonly, BPC 157 microg-ng-rats exhibited consistent functional, biomechanical, macroscopic and histological healing improvements. Thus, we suggest BPC 157 improved healing of acute ligament injuries in further ligament therapy. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury.

PubMed

Gjurasin, Miroslav; Miklic, Pavle; Zupancic, Bozidar; Perovic, Darko; Zarkovic, Kamelija; Brcic, Luka; Kolenc, Danijela; Radic, Bozo; Seiwerth, Sven; Sikiric, Predrag

2010-02-25

We focused on the healing of rat transected sciatic nerve and improvement made by stable gastric pentadecapeptide BPC 157 (10 microg, 10ng/kg) applied shortly after injury (i) intraperitoneally/intragastrically/locally, at the site of anastomosis, or after (ii) non-anastomozed nerve tubing (7 mm nerve segment resected) directly into the tube. Improvement was shown clinically (autotomy), microscopically/morphometrically and functionally (EMG, one or two months post-injury, walking recovery (sciatic functional index (SFI)) at weekly intervals). BPC 157-rats exhibited faster axonal regeneration: histomorphometrically (improved presentation of neural fascicles, homogeneous regeneration pattern, increased density and size of regenerative fibers, existence of epineural and perineural regeneration, uniform target orientation of regenerative fibers, and higher proportion of neural vs. connective tissue, all fascicles in each nerve showed increased diameter of myelinated fibers, thickness of myelin sheet, number of myelinated fibers per area and myelinated fibers as a percentage of the nerve transected area and the increased blood vessels presentation), electrophysiologically (increased motor action potentials), functionally (improved SFI), the autotomy absent. Thus, BPC 157 markedly improved rat sciatic nerve healing. Copyright 2009 Elsevier B.V. All rights reserved.

The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure.

PubMed

Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Konjevoda, P; Perović, D; Jurina, L; Separović, J; Hanzevacki, M; Artuković, B; Bratulić, M; Tisljar, M; Gjurasin, M; Miklić, P; Stancić-Rokotov, D; Slobodnjak, Z; Jelovac, N; Marović, A

1997-07-30

The known effects of a novel stomach pentadecapeptide BPC157 (10 microg or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.)-induced gastric lesions (simultaneously applied i.p.) and in blood pressure maintenance (given i.v.), were investigated in rats challenged with a combination of N(G)-nitro-L-arginine methylester (L-NAME) (5 mg/kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-generation and NO precursor, L-arginine (200 mg/kg i.v.) (D-arginine was ineffective). In the gastric lesions assay, NO agents were given 5 min before ethanol injury and BPC 157 medication. Given alone, BPC157 had an antiulcer effect, as did L-arginine, but L-NAME had no effect. L-NAME completely abolished the effect of L-arginine, whereas it only attenuated the effect of BPC 157. After application of the combination of L-NAME + L-arginine, the BPC157 effect was additionally impaired. In blood pressure studies, compared with L-arginine, pentadecapeptide BPC 157 (without effect on basal normal values) had both a mimicking effect (impaired L-NAME-blood pressure increase, when applied prophylactically and decreased already raised L-NAME values, given at the time of the maximal L-NAME-blood pressure increase (i.e., 10 min after L-NAME)) and preventive activity (L-arginine-induced moderate blood pressure decrease was prevented by BPC 157 pretreatment). When BPC 157 was given 10 min after L-NAME + L-arginine combination, which still led to a blood pressure increase, its previously clear effect (noted in L-NAME treated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 microM) as L-arginine, induced a comparable generation of NO. But, BPC 157 effect could not be inhibited by L-NAME, even when L-NAME was given in a tenfold (100 versus 1000 microM) higher dose than that needed for inhibition of the L-arginine effect. NO synthesis was blunted when the pentadecapeptide BPC 157 and L

Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions.

PubMed

Tlak Gajger, I; Ribarić, J; Smodiš Škerl, M; Vlainić, J; Sikirić, P

2018-04-23

Nosema ceranae can cause major problems, such as immune suppression, gut epithelial cell degeneration, reduced honeybee lifespan, or suddenly colony collapse. As a novel approach in therapy, we hypothesize the stable gastric pentadecapeptide BPC 157 in honeybee therapy, to control N. ceranae invasions in apiary conditions: BPC 157 treated sugar syrup (0.25 L sugar syrup supplemented with 0.1 μg/ml BPC 157), as well as the pure sugar syrup (0.25 L sugar syrup; control), was administered to honeybee colonies in feeders situated under the roof of the hives, during 21 consecutive days, at the end of beekeeping season. The strength of honeybee colonies was increased 20 and 30 days after initial feeding with BPC 157 supplement (Day 1, 36.100 ± 698; Day 20, 64.860 ± 468; Day 30, 53.214 ± 312 estimated number of honeybees), in field conditions. The similar successful outcome occurs with the N. ceranae spore loads counted in the homogenates of sampled adult honeybees (Day 1, 6.286 ± 2.336; Day 20, 3.753 ± 1.835; Day 30, 2.005 ± 1.534 million spores/bee). Accordingly, with the noted increased strength of the colonies fed with sugar syrup supplemented with BPC 157, the number of N. ceranae spores per honeybee gradually decreased as well. Besides, honeybees infected with N. ceranae fed with sugar syrup exhibited severe damage of midgut wall layers and epithelial cells. By contrast, in honeybees infected with N. ceranae fed with sugar syrup supplemented with BPC 157, all damages were markedly attenuated, damages of the outer muscular coat, in particular. In conclusion, the results of the first field trial on diseased honeybee colonies with BPC 157 indicate significant therapeutic effects with the used oral therapy with BPC 157 supplementation. © 2018 John Wiley & Sons Ltd.

Therapy for unhealed gastrocutaneous fistulas in rats as a model for analogous healing of persistent skin wounds and persistent gastric ulcers: stable gastric pentadecapeptide BPC 157, atropine, ranitidine, and omeprazole.

PubMed

Skorjanec, Sandra; Dolovski, Zdravko; Kocman, Ivan; Brcic, Luka; Blagaic Boban, Alenka; Batelja, Lovorka; Coric, Marjana; Sever, Marko; Klicek, Robert; Berkopic, Lidija; Radic, Bozo; Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Cesarec, Vedran; Tonkic, Ante; Zoricic, Ivan; Mise, Stjepan; Staresinic, Mario; Ivica, Mihovil; Lovric Bencic, Martina; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

2009-01-01

This study focused on unhealed gastrocutaneous fistulas to resolve whether standard drugs that promote healing of gastric ulcers may simultaneously have the same effect on cutaneous wounds, and corticosteroid aggravation, and to demonstrate why peptides such as BPC 157 exhibit a greater healing effect. Therefore, with the fistulas therapy, we challenge the wound/growth factors theory of the analogous nonhealing of wounds and persistent gastric ulcers. The healing rate of gastrocutaneous fistula in rat (2-mm-diameter stomach defect, 3-mm-diameter skin defect) validates macro/microscopically and biomechanically a direct skin wound/stomach ulcer relation, and identifies a potential therapy consisting of: (i) stable gastric pentadecapeptide BPC 157 [in drinking water (10 microg/kg) (12 ml/rat/day) or intraperitoneally (10 microg/kg, 10 ng/kg, 10 pg/kg)], (ii) atropine (10 mg/kg), ranitidine (50 mg/kg), and omeprazole (50 mg/kg), (iii) 6-alpha-methylprednisolone (1 mg/kg) [intraperitoneally, once daily, first application at 30 min following surgery; last 24 h before sacrifice (at postoperative days 1, 2, 3, 7, 14, and 21)]. Greater anti-ulcer potential and efficiency in wound healing compared with standard agents favor BPC 157, efficient in inflammatory bowel disease (PL-14736, Pliva), given in drinking water or intraperitoneally. Even after 6-alpha-methylprednisolone aggravation, BPC 157 promptly improves both skin and stomach mucosa healing, and closure of fistulas, with no leakage after up to 20 ml water intragastrically. Standard anti-ulcer agents, after a delay, improve firstly skin healing and then stomach mucosal healing, but not fistula leaking and bursting strength (except for atropine). We conclude that BPC 157 may resolve analogous nonhealing of wounds and persistent gastric ulcers better than standard agents.

Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability.

PubMed

Klicek, R; Kolenc, D; Suran, J; Drmic, D; Brcic, L; Aralica, G; Sever, M; Holjevac, J; Radic, B; Turudic, T; Kokot, A; Patrlj, L; Rucman, R; Seiwerth, S; Sikiric, P

2013-10-01

Stable gastric pentadecapeptide BPC 157 was suggested to link inflammatory bowel disease and multiple sclerosis, and thereby, shown to equally counteract the models of both of those diseases. For colitis, cysteamine (400 mg/kg intrarectally (1 ml/rat)) and colon-colon anastomosis (sacrifice at day 3, 5, 7, and 14) were used. BPC 157 (10 μg/kg, 10 ng/kg) was applied either intraperitoneally once time daily (first application immediately after surgery, last at 24 hours before sacrifice) or per-orally in drinking water (0.16 μg/ml/12 ml/day till the sacrifice) while controls simultaneously received an equivolume of saline (5 ml/kg) intraperitoneally or drinking water only (12 ml/day). A multiple sclerosis suited toxic rat model, cuprizone (compared with standard, a several times higher regimen, 2.5% of diet regimen + 1 g/kg intragastrically/day) was combined with BPC 157 (in drinking water 0.16 μg or 0.16 ng/ml/12 ml/day/rat + 10 μg or 10 ng/kg intragastrically/day) till the sacrifice at day 4. In general, the controls could not heal cysteamine colitis and colon-colon anastomosis. BPC 157 induced an efficient healing of both at the same time. Likewise, cuprizone-controls clearly exhibited an exaggerated and accelerated damaging process; nerve damage appeared in various brain areas, with most prominent damage in corpus callosum, laterodorsal thalamus, nucleus reunions, anterior horn motor neurons. BPC 157-cuprizone rats had consistently less nerve damage in all damaged areas, especially in those areas that otherwise were most affected. Consistently, BPC 157 counteracted cerebellar ataxia and impaired forelimb function. Thereby, this experimental evidence advocates BPC 157 in both inflammatory bowel disease and multiple sclerosis therapy.

High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736).

PubMed

Ilic, S; Drmic, D; Zarkovic, K; Kolenc, D; Coric, M; Brcic, L; Klicek, R; Radic, B; Sever, M; Djuzel, V; Ivica, M; Boban Blagaic, A; Zoricic, Z; Anic, T; Zoricic, I; Djidic, S; Romic, Z; Seiwerth, S; Sikiric, P

2010-04-01

We focused on stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported) because of its hepatoprotective effects. We investigate a particular aspect of the sudden onset of encephalopathy with extreme paracetamol overdose (5 g/kg intraperitoneally) so far not reported: rapidly induced progressive hepatic encephalopathy with generalized convulsions in rats. BPC 157 therapy (10 microg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (microg-ng range) against paracetamol toxicity, given in early (BPC 157 immediately after paracetamol, prophylactically) or advanced stage (BPC 157 at 3 hours after paracetamol, therapeutically). At 25 min post-paracetamol increased ALT, AST and ammonium serum values precede liver lesion while in several brain areas, significant damage became apparent, accompanied by generalized convulsions. Through the next 5 hour seizure period and thereafter, the brain damage, liver damage enzyme values and hyperammonemia increased, particularly throughout the 3-24 h post-paracetamol period. BPC 157 demonstrated clinical (no convulsions (prophylactic application) or convulsions rapidly disappeared (therapeutic effect within 25 min)), microscopical (markedly less liver and brain lesions) and biochemical (enzyme and ammonium serum levels decreased) counteraction. Both, the prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly imply BPC 157 (microg-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose.

Lung lesions and anti-ulcer agents beneficial effect: anti-ulcer agents pentadecapeptide BPC 157, ranitidine, omeprazole and atropine ameliorate lung lesion in rats.

PubMed

Stancic-Rokotov, D; Slobodnjak, Z; Aralica, J; Aralica, G; Perovic, D; Staresinic, M; Gjurasin, M; Anic, T; Zoricic, I; Buljat, G; Prkacin, I; Sikiric, P; Seiwerth, S; Rucman, R; Petek, M; Turkovic, B; Kokic, N; Jagic, V; Boban-Blagaic, A

2001-01-01

Anti-ulcer agents may likely attenuate lesions outside the gastrointestinal tract, since they had protected gastrectomized rats (a "direct cytoprotective effect"). Therefore, their therapeutic potential in lung/stomach lesions were shown. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung lesion), and an intragastric (i.g.) instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), then sacrificed 1 h after ethanol. Basically, in lung-injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for 1 h of observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (i) once, only prophylactically [as a pre-treatment (at -1h)], or as a co-treatment [at 0)], or only therapeutically (at +18h or +24 h); (ii) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h)] or [(0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. For all agents, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) attenuated lung lesions; even if effect had been not seen already with a single application, it became prominent after repeated treatment. In single application studies, relative to controls, a co-treatment (except to omeprazole), a pre-treatment (at -1 h) (pentadecapeptide BPC 157 and atropine, but not ranitidine and omeprazole) regularly attenuated, while therapeutically, atropine (at +18 h), pentadecapeptide BPC 157 highest dose and omeprazole (at +24 h), reversed the otherwise more severe lung lesions.

Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats.

PubMed

Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Ljubanović, D; Separović, J; Gjurasin, M; Bratulić, M; Artuković, B; Jelovac, N; Buljat, G

1996-07-01

The superior effectiveness of a new pentadecapeptide, BPC 157, on gastrointestinal and liver lesions, in conjunction with an antiinflammatory and analgetic activity was recently noted. In the present study, BPC 157 was tested as either a protective or healing agent in bile duct ligation-induced acute pancreatitis in rats. In addition, the positive influence of BPC 157 on concomitantly developed gastric and duodenal lesions was simultaneously investigated. BPC 157 (10 microg, 10 ng/kg body wt, intraperitoneally or intragastrically) was given prophylactically 1 hr before ligation, whereas the therapy was given once daily beginning with the 24 hr following ligation (last application 24 hr before killing). The effect was investigated at daily intervals until the end of the fifth day after ligation. In the pretreatment regimen, a strong pancreas protection was obtained. When applied in the condition of already established severe acute pancreatitis, an obvious salutory effect was consistently noted. Assessing the appearance of the necrosis, edema, neutrophils, and mononuclears, consistently less necrosis, edema, and neutrophils, but more mononuclears, were found in BPC-treated rats. Likewise, in studies of the serum amylase values, relative to control data, a markedly lower rise (BPC pretreatment regimen) as well as a worsening of the already raised values (BPC therapy regimen) was noted. Along with its beneficial effect on pancreatitis, a positive influence of BPC 157 on the gastric and duodenal lesion course in bile duct-ligated rats was noted in both the pre- and posttreatment regimen. Taken together, in further studies of acute pancreatitis therapy, BPC could be an interesting and useful agent with an additional positive impact on concomitant gastroduodenal pathology.

An experimental model of prolonged esophagitis with sphincter failure in the rat and the therapeutic potential of gastric pentadecapeptide BPC 157.

PubMed

Petrovic, Igor; Dobric, Ivan; Drvis, Petar; Shejbal, Drazen; Brcic, Luka; Blagaic, Alenka Boban; Batelja, Lovorka; Kokic, Neven; Tonkic, Ante; Mise, Stjepan; Baotic, Tomislav; Staresinic, Mario; Radic, Bozo; Jakir, Ana; Vuksic, Tihomir; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

2006-11-01

We report a simple novel rat model that combines prolonged esophagitis and parallel sphincters failure. The anti-ulcer gastric pentadecapeptide BPC 157, which was found to be stable in gastric juice, and is being evaluated in inflammatory bowel disease trials, is an anti-esophagitis therapy that recovers failed sphincters. Twelve or twenty months after the initial challenge (tubes sutured into sphincters for one week and then spontaneously removed by peristalsis), rats exhibit prolonged esophagitis (confluent hemorrhagic and yellowish lesions, thinner epithelium and superficial corneal layer, with stratification derangement); constantly lowered pressure of both sphincters (assessed by using a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through esophageal or duodenal incision); and both lower esophageal and pyloric sphincter failure. Throughout the esophagitis experiment, BPC 157 was given at either 10 micro g/kg, i.p., once a day (last application 24 h before assessment) or alternatively, it was given continuously in drinking water at 0.16 micro g/ml (12 ml/rat). This treatment recovers i) esophagitis (macroscopically and microscopically, at either region or investigated time period) and ii) pressure in both sphincters (cmH2O). In addition, BPC 157 (10 micro g/kg) or saline (1 ml/rat, 5 ml/kg) was specifically given directly into the stomach; pressure assessment was performed at 5 min thereafter. The effect of BPC 157 is specific because in normal rats, it increases lower esophageal sphincter-pressure, but decreases pyloric sphincter-pressure. Ranitidine, given as the standard drug using the same protocol (50 mg/kg, i.p., once daily; 0.83 mg/ml in drinking water; or 50 mg/kg directly into the stomach) had no effect.

Traumatic brain injury in mice and pentadecapeptide BPC 157 effect.

PubMed

Tudor, Mario; Jandric, Ivan; Marovic, Anton; Gjurasin, Miroslav; Perovic, Darko; Radic, Bozo; Blagaic, Alenka Boban; Kolenc, Danijela; Brcic, Luka; Zarkovic, Kamelija; Seiwerth, Sven; Sikiric, Predrag

2010-02-25

Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an anti-ulcer peptide, efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported, improved muscle crush injury. After an induced traumatic brain injury (TBI) in mice by a falling weight, BPC 157 regimens (10.0microg, 10.0ng/kgi.p.) demonstrated a marked attenuation of damage with an improved early outcome and a minimal postponed mortality throughout a 24h post-injury period. Ultimately, the traumatic lesions (subarachnoidal and intraventricular haemorrhage, brain laceration, haemorrhagic laceration) were less intense and consecutive brain edema had considerably improved. Given prophylactically (30 min before TBI) the improved conscious/unconscious/death ratio in TBI-mice was after force impulses of 0.068 Ns, 0.093 Ns, 0.113 Ns, 0.130 Ns, 0.145 Ns, and 0.159 Ns. Counteraction (with a reduction of unconsciousness, lower mortality) with both microg- and ng-regimens included the force impulses of 0.068-0.145 Ns. A higher regimen presented effectiveness also against the maximal force impulse (0.159 Ns). Furthermore, BPC 157 application immediately prior to injury was beneficial in mice subjected to force impulses of 0.093 Ns-TBI. For a more severe force impulse (0.130 Ns, 0.145 Ns, or 0159 Ns), the time-relation to improve the conscious/unconscious/death ratio was: 5 min (0.130 Ns-TBI), 20 min (0.145 Ns-TBI) or 30 min (0.159 Ns-TBI). Copyright 2009 Elsevier B.V. All rights reserved.

Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.

PubMed

Sikiric, P; Seiwerth, S; Grabarevic, Z; Balen, I; Aralica, G; Gjurasin, M; Komericki, L; Perovic, D; Ziger, T; Anic, T; Prkacin, I; Separovic, J; Stancic-Rokotov, D; Lovric-Bencic, M; Mikus, D; Staresinic, M; Aralica, J; DiBiaggio, N; Simec, Z; Turkovic, B; Rotkvic, I; Mise, S; Rucman, R; Petek, M; Sebecic, B; Ivasovic, Z; Boban-Blagaic, A; Sjekavica, I

2001-01-01

Recently, we showed cysteamine-duodenal lesions without gastric acid, since they were induced also in gastrectomized rats, as in naive rats, and they were inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine, atropine). Therefore, as an advantage of considering cysteamine as a directly acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the present focus was on the ulcerogenic effect of cysteamine and protective effect of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w) produced severe colon lesions (i.e. transmural inflammation with serosal involvement) in rats (30 min-72 h-experimental period), apparently distinctive from smaller lesions after non-specific irritant enema [diluted HCl solution, pH 3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer agents were applied simultaneously with cysteamine enema (8 cm from the anus, in a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.), given in either regimen, previously shown to have, besides others, a particular beneficial activity just in the intestinal mucosa, inhibited these cysteamine colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g., or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.), assessed 30 min following application of 200 mg of cysteamine. Finally, standard cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of 400 mg/kg of cysteamine) were

Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia) heals ileoileal anastomosis in the rat.

PubMed

Vuksic, Tihomir; Zoricic, Ivan; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Cesarec, Vedran; Berkopic, Lidija; Keller, Neike; Blagaic, Alenka Boban; Kokic, Neven; Jelic, Ivan; Geber, Juraj; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

2007-01-01

Gastric pentadecapeptide BPC 157 (BPC 157), which has been shown to be safe in clinical trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia), may be able to cure intestinal anastomosis dehiscence. This antiulcer peptide shows no toxicity, is limit test negative, and a lethal dose is not achieved. It is stable in human gastric juice. In comparison with other standard treatments it is more effective for ulcers and various wounds, and can be used without a carrier needed for other peptides, both locally and systemically (i.e., perorally, parenterally). We studied the effectiveness of BPC 157 for ileoileal anastomosis healing in rats. We assessed ileoileal anastomosis dehiscence macroscopically, histologically, and biomechanically (volume [ml] infused through a syringe-perfusion pump system (1 ml/10 s), and pressure [mmHg] to leak induction [catheter connected to a chamber and a monitor, at 10 cm proximal to anastomosis]), at 1, 2, 3, 4, 5, 6, 7, and 14 days. BPC 157 (10 microg, 10 ng, 10 pg/kg i.p. (or saline [5 ml/kg]) was first administered after surgery, while it was last given 24 h before either assessment or sacrifice. Throughout the experiment, both higher doses of BPC 157 were shown to improve all parameters of anastomotic wound healing. The formation of adhesions remained slight, the blood vessels were filled with blood, and a mild intestinal passage obstruction was only temporarily observed. Anastomosis without leakage induces markedly higher volume and pressure values, with a continuous increase toward healthy values. From day 1, edema was markedly attenuated and the number of granulocytes decreased, while from days 4 or 5 necrosis decreased and granulation tissue, reticulin, and collagen formation substantially increased, thus resulting in increased epithelization. This study showed BPC 157 to have a beneficial effect on ileoileal anastomosis healing in the rat.

Pentadecapeptide BPC 157 attenuates gastric lesions induced by alloxan in rats and mice.

PubMed

Petek, M; Sikiric, P; Anic, T; Buljat, G; Separovic, J; Stancic-Rokotov, D; Seiwerth, S; Grabarevic, Z; Rucman, R; Mikus, D; Zoricic, I; Prkacin, I; Sebecic, B; Ziger, T; Coric, V; Turkovic, B; Aralica, G; Rotkvic, I; Mise, S; Hahn, V

1999-12-01

A diabetogenic alloxan regimen produced lesions in all stomachs of treated animals, either rats (200 mg x kg(-1) s.c.) or mice (400 mg x kg(-1) i.p.). In control animals, the lesions, when developed (i.e. 24 h following application), appear to be quite sustained, and consistently present also after 1 or 2 weeks. The application of the pentadecapeptide BPC 157 (10 microg or 10 ng x kg(-1) i.p. coadministered together with alloxan) would significantly attenuate these lesions' appearance. This beneficial effect seems to be present in either rats or mice and in either of the tested intervals. Importantly, the beneficial effect seems to be shared by both microgram and nanogram regimens.

Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157.

PubMed

Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Duplancic, B; Marovic, A; Zoricic, I; Prkacin, I; Lovric-Bencic, M; Aralica, G; Ziger, T; Perovic, D; Jelovac, N; Dodig, G; Rotkvic, I; Mise, S; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R

2000-01-01

Up to now, for gastric lesions potentiation or induction, as well as determination of endogenous dopamine significance, dopamine antagonist or dopamine vesicle depletor were given separately. Therefore, without combination studies, the evidence for dopamine significance remains split on either blockade of dopamine post-synaptic receptor or inhibition of dopamine storage, essentially contrasting with endogenous circumstances, where both functions could be simultaneously disturbed. For this purpose, a co-administration of reserpine and haloperidol, a dopamine granule depletor combined with a dopamine antagonist with pronounced ulcerogenic effect, was tested, and the rats were sacrificed 24 h after injurious agent(s) administration. Haloperidol (5 mg x kg(-1) b.w. i.p.), given alone, produced the lesions in all rats. Reserpine (5 mg x kg(-1) b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger than in the groups injured with separate administration of either haloperidol or reserpine alone. Along with our previous results, when beneficial agents were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomophine 1 mg, amphetamine 20 mg x kg(-1) i.p.) apparently attenuated the otherwise consistent haloperidol-gastric lesions. Likewise, an apparent inhibition of the reserpine-lesions was noted as well. However, if they were given in rats injured with combination of haloperidol and reserpine, their otherwise prominent beneficial effects were absent. Ranitidine (10 mg), omeprazole (10 mg), atropine (10 mg), pentadecapeptide BPC 157 (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) (10 microg or 10 ng x kg(-1) i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. Confronted with potentiated lesions following a combination of haloperidol and reserpine, these agents maintained their beneficial effects, noted in the rats treated with either

Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system.

PubMed

Balenovic, Dijana; Bencic, Martina Lovric; Udovicic, Mario; Simonji, Karol; Hanzevacki, Jadranka Separovic; Barisic, Ivan; Kranjcevic, Stjepan; Prkacin, Ingrid; Coric, Vedran; Brcic, Luka; Coric, Marijana; Brcic, Iva; Borovic, Suzana; Radic, Bozo; Drmic, Domagoj; Vrcic, Hrvoje; Seiwerth, Sven; Sikiric, Predrag

2009-08-07

Pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419) reversed congestive heart failure and various arrhythmias, influenced the NO-system and showed no proarrhythmic effect. In therapy analogy, we challenged rats with digitalis, to show attenuation by BPC 157 and the relation between the NO-system and digitalis toxicity. (i). BPC 157 prophylactic effect. Development of cumulative intravenous digitalis toxicity, BPC 157 (50 microg, 10 microg, 10 ng/kg applied intravenously immediately before a methyldigoxin increment regimen (2.0/1.5/1.5/1.0 mg/kg at 15 min-intervals, total dose 6.0 mg/kg/45 min)) reduced the number of ventricular premature beats, prolonged the time before onset of ventricular tachycardia, reduced ventricular tachycardia and AV-block duration (microg-regimes) or reduced mainly the AV-block duration (ng-regimen). (ii). BPC 157 therapy. Advanced methyldigoxin toxicity (6.0 mg/kg i.v. bolus). BPC 157 applied at the 20th second of the grade 3 AV-block shortened AV-blocks, mitigated a further digitalis toxicity course. Ventricular tachycardias were either avoided (50 microg), or markedly reduced (10 microg, 10 ng). Fatal outcome was either avoided (50 microg), reduced (10 microg), or only delayed (10 ng) (iii) BPC 157, L-NAME, l-arginine, L-NAME+l-arginine application. L-NAME-application (5 mg/kg i.p.) aggravated methyldigoxin-arrhythmias. l-arginine (200 mg/kg i.p.) alone had no effect but blunted L-NAME-exaggeration (L-NAME+l-arginine). In this respect, BPC 157 (50 microg/kg i.p.) was prophylactically and therapeutically more effective: the antagonism of L-NAME with BPC 157 produced an effect similar to BPC 157 alone. In conclusion, digitalis-induced arrhythmias in rats could be prevented and counteracted by pentadecapeptide BPC 157, mainly through an interaction with the NO-system.

Pentadecapeptide BPC 157 positively affects both non-steroidal anti-inflammatory agent-induced gastrointestinal lesions and adjuvant arthritis in rats.

PubMed

Sikiric, P; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Rotkvic, I; Mise, S; Zoricic, I; Konjevoda, P; Perovic, D; Simicevic, V; Separovic, J; Hanzevacki, M; Ljubanovic, D; Artukovic, B; Bratulic, M; Tisljar, M; Rekic, B; Gjurasin, M; Miklic, P; Buljat, G

1997-01-01

Besides a superior protection of the pentadecapeptide BPC 157 (an essential fragment of an organoprotective gastric juice peptide BPC) against different gastrointestinal and liver lesions, an acute anti-inflammatory and analgetic activity was also noted. Consequently, its effect on chronic inflammation lesions, such as adjuvant arthritis, and non-steroidal anti-inflammatory agents (NSAIAs)-induced gastrointestinal lesions was simultaneously studied in rats. In gastrointestinal lesions (indomethacin (30 mg/kg s.c.), aspirin (400 mg/kg i.g.) and diclofenac (125 mg/kg i.p.) studies, BPC 157 (10 micrograms or 10 ng/kg i.p.) was regularly given simultaneously and/or 1 h prior to drug application (indomethacin). In the adjuvant arthritis (tail-application of 0.2 mL of Freund's adjuvant) studies (14 days, 30 days, 1 year) BPC 157 (10 micrograms or 10 ng/kg i.p.), it was given as a single application (at 1 h either before or following the application of Freund's adjuvant) or in a once daily regimen (0-14th day, 14-30th day, 14th day-1 year). Given with the investigated NSAIAs, BPC 157 consistently reduced the otherwise prominent lesions in the stomach of the control rats, as well as the lesions in the small intestine in the indomethacin groups. In the adjuvant arthritis studies, the lesion's development seems to be considerably reduced after single pentadecapeptide medication, and even more attenuated in rats daily treated with BPC 157. As a therapy of already established adjuvant arthritis, its salutary effect consistently appeared already after 2 weeks of medication and it could be clearly seen also after 1 year of application. Taking together all these results, the data likely point to a special anti-inflammatory and mucosal integrity protective effect.

Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine.

PubMed

Prkacin, I; Separovic, J; Aralicia, G; Perovic, D; Gjurasin, M; Lovric-Bencic, M; Stancic-Rokotov, D; Staresinic, M; Anic, T; Mikus, D; Sikiric, P; Seiwerth, S; Mise, S; Rotkvic, I; Jagic, V; Rucman, R; Petek, M; Turkovic, B; Marovic, A; Sebecic, B; Boban-Blagaic, A; Kokic, N

2001-01-01

Liver lesions and portal hypertension in rats, following chronic alcohol administration, are a particular target for therapy. Portal hypertension (mm Hg) assessed directly into the portal vein, and liver lesions induced by 7.28 g/kg b.w. of alcohol given in drinking water for 3 months, were counteracted by a stable gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in a variety of models of gastrointestinal or liver lesions (10 microg or 10 ng/kg b.w. i.p. or i.g.) and propranolol (10 mg/kg b.w. i.g.), but not ranitidine (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). The medication (once daily) was throughout either the whole 3 months period (1) or the last month only (2) (last application 24 h before sacrifice). In the background of 7.28 g/kg/daily alcohol regimen similar lesions values were assessed in control rats following alcohol consumption, after 2 or 3 months of drinking. Both prophylactic and therapeutic effects were shown. After a period of 2 or 3 months, in all control saline [intragastrically (i.g.) or intraperitoneally (i.p.)] treated rats, the applied alcohol regimen consistently induced a significant rise of portal blood pressure values over values noted in healthy rats. In rats that received gastric pentadecapeptide BPC 157 or propranolol the otherwise raised portal pressure was reduced to the values noted in healthy rats. Besides, a raised surface area (microm(2)) and increased circumference (microm) of hepatocyte or hepatocyte nucleus [HE staining, measured using PC-compatible program ISSA (VAMS, Zagreb, Croatia)] and an advanced steatosis [scored (0-4), Oil Red staining] (on 100 randomly assigned hepatocytes per each liver), an increased liver weight, all together parallel a raised portal pressure in controls. Some of them were completely eliminated (not different from healthy rats, i.e. portal pressure, the circumference and area of hepatocytes, liver weight), while others were

Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin.

PubMed

Stupnisek, Mirjana; Franjic, Sandra; Drmic, Domagoj; Hrelec, Masa; Kolenc, Danijela; Radic, Bozo; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2012-05-01

Recently, in rat abdominal aorta terminoterminal-anastomosis the stable gastric pentadecapeptide BPC 157 prevents obstructive thrombus formation and rapidly destroys already formed obstructive thrombus. Also, BPC 157 wound healing may signify the clot as conductive matrix or "scaffold" to speed up wound healing process, and decrease bleeding. Here, in rats, BPC 157 (10 μg/kg, 10 ng/kg) improved always reduced bleeding time and amount of bleeding after (tail) amputation only, heparin (250 mg/kg, 25mg/kg, 10mg/kg i.v.), warfarin (1.5mg/kg i.g. once daily for 3 consecutive days), aspirin (0.1g/kg i.g. (once daily/3 consecutive days) or 1.0 g/kg i.p. once), and amputation associated with those agents application. BPC 157 counteracting regimens (i.v., i.p., i.g. (immediately after any challenge)) correspondingly follow the route of bleeding-agents application. All heparin-, warfarin-, and aspirin-rats and normal-rats that received BPC 157 exhibited lesser fall in platelets count. BPC 157 attenuated over-increased APTT-, TT-values in 10mg/kg heparin-rats, but did not influence heparin activity (anti-Xa test). Indicatively, unless counteracted in BPC 157 rats, excessive bleeding-acute thrombocytopenia (<20% of initial values in heparin-rats) approaches substantial fall in platelets count known in type II HIT. Also, BPC 157 markedly prolongs the survival time (heparin-rats, 25mg/kg, right foot amputation). Copyright © 2011 Elsevier Ltd. All rights reserved.

The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.

PubMed

Chang, Chung-Hsun; Tsai, Wen-Chung; Lin, Miao-Sui; Hsu, Ya-Hui; Pang, Jong-Hwei Su

2011-03-01

Pentadecapeptide BPC 157, composed of 15 amino acids, is a partial sequence of body protection compound (BPC) that is discovered in and isolated from human gastric juice. Experimentally it has been demonstrated to accelerate the healing of many different wounds, including transected rat Achilles tendon. This study was designed to investigate the potential mechanism of BPC 157 to enhance healing of injured tendon. The outgrowth of tendon fibroblasts from tendon explants cultured with or without BPC 157 was examined. Results showed that BPC 157 significantly accelerated the outgrowth of tendon explants. Cell proliferation of cultured tendon fibroblasts derived from rat Achilles tendon was not directly affected by BPC 157 as evaluated by MTT assay. However, the survival of BPC 157-treated cells was significantly increased under the H(2)O(2) stress. BPC 157 markedly increased the in vitro migration of tendon fibroblasts in a dose-dependent manner as revealed by transwell filter migration assay. BPC 157 also dose dependently accelerated the spreading of tendon fibroblasts on culture dishes. The F-actin formation as detected by FITC-phalloidin staining was induced in BPC 157-treated fibroblasts. The protein expression and activation of FAK and paxillin were determined by Western blot analysis, and the phosphorylation levels of both FAK and paxillin were dose dependently increased by BPC 157 while the total amounts of protein was unaltered. In conclusion, BPC 157 promotes the ex vivo outgrowth of tendon fibroblasts from tendon explants, cell survival under stress, and the in vitro migration of tendon fibroblasts, which is likely mediated by the activation of the FAK-paxillin pathway.

Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress.

PubMed

Sikirić, P; Mazul, B; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Gjurasin, M; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Miklić, P; Sumajstorcić, J

1997-03-01

Since superior protection against different gastrointestinal and liver lesions and antiinflammatory and analgesic activities were noted for pentadecapeptide BPC (an essential fragment of an organoprotective gastric juice protein named BPC), the beneficial mechanism of BPC 157 and its likely interactions with other systems were studied. Hence its beneficial effects would be abolished by adrenal gland medullectomy, the influence of different agents affecting alpha, beta, and dopamine receptors on BPC 157 gastroprotection in 48 h restraint stress was further investigated. Animals were pretreated (1 hr before stress) with saline (controls) or BPC 157 (dissolved in saline) (10 microg or 10 ng/kg body wt intraperitoneally or intragastrically) applied either alone to establish basal conditions or, when manipulating the adrenergic or dopaminergic system, a simultaneous administration was carried out with various agents with specific effects on adrenergic or dopaminergic receptors [given in milligrams per kilogram intraperitoneally except for atenolol, which was given subcutaneously] phentolamine (10.0), prazosin (0.5), yohimbine (5.0), clonidine (0.1) (alpha-adrenergic domain), propranolol (1.0), atenolol (20.0) (beta-adrenergic domain), domperidone (5.0), and haloperidol (5.0) (peripheral/central dopamine system). Alternatively, agents stimulating adrenergic or dopaminergic systems--adrenaline (5.0) or bromocriptine (10.0)--were applied. A strong protection, noted following intragastric or intraperitoneal administration of BPC 157, was fully abolished by coadministration of phentolamine, clonidine, and haloperidol, and consistently not affected by prazosin, yohimbine, or domperidone. Atenolol abolished only intraperitoneal BPC 157 protection, whereas propranolol affected specifically intragastric BPC 157 protection. Interestingly, the severe course of lesion development obtained in basal conditions, unlike BPC 157 gastroprotection, was not influenced by the application of

Mortal hyperkalemia disturbances in rats are NO-system related. The life saving effect of pentadecapeptide BPC 157.

PubMed

Barisic, Ivan; Balenovic, Diana; Klicek, Robert; Radic, Bozo; Nikitovic, Bojana; Drmic, Domagoj; Udovicic, Mario; Strinic, Dean; Bardak, Darija; Berkopic, Lidija; Djuzel, Viktor; Sever, Marko; Cvjetko, Ivan; Romic, Zeljko; Sindic, Aleksandra; Bencic, Martina Lovric; Seiwerth, Sven; Sikiric, Predrag

2013-02-10

We demonstrate the full counteracting ability of stable gastric pentadecapeptide BPC 157 against KCl-overdose (intraperitoneal (i), intragastric (ii), in vitro (iii)), NO-system related. (i) We demonstrated potential (/kg) of: BPC 157 (10ng, 10μg ip, complete counteraction), l-arginine (100mg ip, attenuation) vs. L-NAME (5mg ip, deadly aggravation), given alone and/or combined, before or after intraperitoneal KCl-solution application (9mEq/kg). Therapy was confronted with promptly unrelenting hyperkalemia (>12mmol/L), arrhythmias (and muscular weakness, hypertension, low pressure in lower esophageal and pyloric sphincter) with an ultimate and a regularly inevitable lethal outcome within 30min. Previously, we established BPC 157-NO-system interaction; now, a huge life-saving potential. Given 30min before KCl, all BPC 157 regimens regained sinus rhythm, had less prolongation of QRS, and had no asystolic pause. BPC 157 therapy, given 10min after KCl-application, starts the rescue within 5-10min, completely restoring normal sinus rhythm at 1h. Likewise, other hyperkalemia-disturbances (muscular weakness, hypertension, low sphincteric pressure) were also counteracted. Accordingly with NO-system relation, deadly aggravation by L-NAME: l-arginine brings the values to the control levels while BPC 157 always completely nullified lesions, markedly below those of controls. Combined with l-arginine, BPC 157 exhibited no additive effect. (ii) Intragastric KCl-solution application (27mEq/kg) - (hyperkalemia 7mmol/L): severe stomach mucosal lesions, sphincter failure and peaked T waves were fully counteracted by intragastric BPC 157 (10ng, 10μg) application, given 30min before or 10min after KCl. (iii). In HEK293 cells, hyperkalemic conditions (18.6mM potassium concentrations), BPC 157 directly affects potassium conductance, counteracting the effect on membrane potential and depolarizations caused by hyperkalemic conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Hypermagnesemia disturbances in rats, NO-related: pentadecapeptide BPC 157 abrogates, L-NAME and L-arginine worsen.

PubMed

Medvidovic-Grubisic, Maria; Stambolija, Vasilije; Kolenc, Danijela; Katancic, Jadranka; Murselovic, Tamara; Plestina-Borjan, Ivna; Strbe, Sanja; Drmic, Domagoj; Barisic, Ivan; Sindic, Aleksandra; Seiwerth, Sven; Sikiric, Predrag

2017-08-01

Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects. Assessment included magnesium sulfate (560 mg/kg intraperitoneally)-induced muscle weakness, muscle and brain lesions, hypermagnesemia, hyperkalaemia, increased serum enzyme values assessed in rats during and at the end of a 30-min period and medication (given intraperitoneally/kg at 15 min before magnesium) [BPC 157 (10 µg, 10 ng), L-NAME (5 mg), L-arginine (100 mg), alone and/or together]. In HEK293 cells, the increasing magnesium concentration from 1 to 5 mM could depolarize the cells at 1.75 ± 0.44 mV. L-NAME + magnesium-rats and L-arginine + magnesium-rats exhibited worsened severe muscle weakness and lesions, brain lesions, hypermagnesemia and serum enzymes values, with emerging hyperkalaemia. However, L-NAME + L-arginine + magnesium-rats exhibited all control values and normokalaemia. BPC 157 abrogated hypermagnesemia and counteracted all of the magnesium-induced disturbances (including those aggravated by L-NAME or L-arginine). Thus, cell depolarization due to increasing magnesium concentration was inhibited in the presence of BPC 157 (1 µM) in vitro. BPC 157 likely counteracts the initial event leading to hypermagnesemia and the life-threatening actions after a magnesium overdose. In contrast, a worsened clinical course, higher hypermagnesemia, and emerging hyperkalaemia might cause both L-NAME and L-arginine to affect the same events adversely. These events were also opposed by BPC 157.

Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions.

PubMed

Ilic, Spomenko; Drmic, Domagoj; Franjic, Sandra; Kolenc, Danijela; Coric, Marijana; Brcic, Luka; Klicek, Robert; Radic, Bozo; Sever, Marko; Djuzel, Viktor; Filipovic, Marinko; Djakovic, Zeljko; Stambolija, Vasilije; Blagaic, Alenka Boban; Zoricic, Ivan; Gjurasin, Miroslav; Stupnisek, Mirjana; Romic, Zeljko; Zarkovic, Kamelija; Dzidic, Senka; Seiwerth, Sven; Sikiric, Predrag

2011-03-14

We attempted to fully antagonize the extensive toxicity caused by NSAIDs (using diclofenac as a prototype). Herein, we used the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), an anti-ulcer peptide shown to be efficient in inflammatory bowel disease clinical trials (PL 14736) and various wound treatments with no toxicity reported. This peptide was given to antagonize combined gastrointestinal, liver, and brain toxicity induced by diclofenac (12.5mg/kg intraperitoneally, once daily for 3 days) in rats. Already considered a drug that can reverse the toxic side effects of NSAIDs, BPC 157 (10 μg/kg, 10 ng/kg) was strongly effective throughout the entire experiment when given (i) intraperitoneally immediately after diclofenac or (ii) per-orally in drinking water (0.16 μg/mL, 0.16 ng/mL). Without BPC 157 treatment, at 3h following the last diclofenac challenge, we encountered a complex deleterious circuit of diclofenac toxicity characterized by severe gastric, intestinal and liver lesions, increased bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) serum values, increased liver weight, prolonged sedation/unconsciousness (after any diclofenac challenge) and finally hepatic encephalopathy (brain edema particularly located in the cerebral cortex and cerebellum, more in white than in gray matter, damaged red neurons, particularly in the cerebral cortex and cerebellar nuclei, Purkinje cells and less commonly in the hippocampal neurons). The very extensive antagonization of diclofenac toxicity achieved with BPC 157 (μg-/ng-regimen, intraperitoneally, per-orally) may encourage its further use as a therapy to counteract diclofenac- and other NSAID-induced toxicity. Copyright © 2011 Elsevier Inc. All rights reserved.

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine.

PubMed

Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2015-01-01

BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)-rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157 μg+L-NAME; BPC 157 μg+L-arginine, BPC 157 μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms.

Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice.

PubMed

Bilic, I; Zoricic, I; Anic, T; Separovic, J; Stancic-Rokotov, D; Mikus, D; Buljat, G; Ivankovic, D; Aralica, G; Prkacin, I; Perovic, D; Mise, S; Rotkvic, I; Petek, M; Rucman, R; Seiwerth, S; Sikiric, P

2001-03-09

The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.

Impact of pentadecapeptide BPC 157 on muscle healing impaired by systemic corticosteroid application.

PubMed

Pevec, Danira; Novinscak, Tomislav; Brcic, Luka; Sipos, Kristijan; Jukic, Ivana; Staresinic, Mario; Mise, Sandro; Brcic, Iva; Kolenc, Danijela; Klicek, Robert; Banic, Tihomir; Sever, Marko; Kocijan, Ana; Berkopic, Lidija; Radic, Bozo; Buljat, Gojko; Anic, Tomislav; Zoricic, Ivan; Bojanic, Ivan; Seiwerth, Sven; Sikiric, Predrag

2010-03-01

The effect of systemic and local peptide treatment effective in muscle contusion and then on counteraction of corticosteroid-induced impairment was tested. The pentadecapeptide BPC 157, given without a carrier, improved the healing of transected quadriceps muscle. It also improved muscle healing in rats with muscle crush injury when applied systemically or locally. Importantly, it counteracted corticosteroid-impairment in tendon to bone healing. Thus BPC 157 is proposed as an effective treatment that can improve muscle healing in spite of corticosteroid treatment. After the gastrocnemius muscle complex had been injured, rats received BPC 157 (intraperitoneally or locally as a cream) and/or 6alpha-methylprednisolone (intraperitoneally) only once (immediately after injury, sacrifice at 2 h) or once daily (final dose 24 hours before sacrifice and/or assessment procedure at days 1, 2, 4, 7, and 14). Muscle healing was evaluated functionally, macroscopically, and histologically. Without therapy, crushed gastrocnemius muscle complex controls showed limited improvement. 6alpha-methylprednisolone markedly aggravated healing. In contrast, BPC 157 induced faster muscle healing and full function restoration and improved muscle healing despite systemic corticosteroid treatment when given intraperitoneally or locally and demonstrated functionally, macroscopically, and histologically at all investigated intervals. BPC 157 completely reversed systemic corticosteroid-impaired muscle healing.

BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats.

PubMed

Strinic, Dean; Belosic Halle, Zeljka; Luetic, Kresimir; Nedic, Ana; Petrovic, Igor; Sucic, Mario; Zivanovic Posilovic, Gordana; Balenovic, Dijana; Strbe, Sanja; Udovicic, Mario; Drmic, Domagoj; Stupnisek, Mirjana; Lovric Bencic, Martina; Seiwerth, Sven; Sikiric, Predrag

2017-10-01

Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10μg, 10ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0mg/kg ip), fluphenazine (0.5, 5.0mg/kg ip), clozapine (1.0, 10.0mg/kg ip), quetiapine (1.0, 10.0mg/kg ip), sulpiride (1.6, 16.0mg/kg ip), metoclopramide (2.5, 25.0mg/kg ip) or (1.0, 10.0mg/kg ip). Controls simultaneously received saline (5ml/kg ip). To assess the ECG presentation before and after neuroleptic/prokinetic medication, the assessment was at 1, 2, 3, 4, 5, 10, 15, 20 and 30min (first administration) as well as at 30min, 60min and 24h (first administration and subsequent administrations) and the ECG recording started prior to drug administration. Since very early, a prolonged QTc interval has been continually noted with haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats as a central common effect not seen with domperidone. Consistent counteraction appears with the stable gastric pentadecapeptide BPC 157. Thus, BPC 157 rapidly and permanently counteracts the QTc prolongation induced by neuroleptics and prokinetics. Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval. Copyright © 2017 Elsevier Inc. All rights reserved.

A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine.

PubMed

Sikiric, P; Marovic, A; Matoz, W; Anic, T; Buljat, G; Mikus, D; Stancic-Rokotov, D; Separovic, J; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Ziger, T; Sebecic, B; Zoricic, I; Turkovic, B; Aralica, G; Perovic, D; Duplancic, B; Lovric-Bencic, M; Rotkvic, I; Mise, S; Jagic, V; Hahn, V

1999-12-01

The effect of a stomach pentadecapeptide, BPC 157, on Parkinson's disease in mice was investigated, along with its salutary activity on stomach lesions induced by parkinsongenic agents. Parkinsongenic agents, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30.0 mg x kg(-1)b.w. i.p. once daily for 6d, and after 4d once 50.0 mg x kg(-1)b.w. i.p.) or reserpine (5.0 mg x kg(-1)b.w. i.p.) were applied i.p. BPC 157 (1.50 microg or 15.0 ng x kg(-1)b.w. i.p.) was applied 15 min before or alternatively 15 min after each MPTP administration. In reserpine studies, BPC 157 (10.0 microg or 10.0 ng x kg(-1)b.w. i.p.) was given either 15 min before reserpine or in the already established complete catalepsy 24 h thereafter. BPC 157 strongly improved the MPTP-impaired somatosensory orientation and reduced the MPTP-induced hyperactivity, and most importantly, MPTP-motor abnormalities (tremor, akinesia, catalepsy -otherwise very prominent in saline control), leading to almost complete abolition of otherwise regularly lethal course of MPTP treatment in controls. Likewise, in reserpine experiments, BPC 157 strongly prevented the development of otherwise very prominent catalepsy and when applied 24 h thereafter reversed the established catalepsy. In addition, a reduction of reserpine-hypothermy (BPC 157 pre-treatment) and reversal of further prominent temperature fall (BPC 157 post-treatment) have been consistently observed. Taking together these data, as the two most suitable animal models were consistently used and since the high effectiveness was demonstrated in pre- and post-treatment, microg and ng regimens, BPC 157 as an organoprotector should be further therapeutically investigated. Additionally, given in either regimen, pentadecapeptide BPC 157 strongly attenuated the stomach lesions in mice that otherwise consistently appeared in mice treated with the parkinsogenic neurotoxin MPTP.

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

PubMed Central

Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2015-01-01

Background BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Methods Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. Results After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. Conclusions L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms. PMID:25897838

The effect of pentadecapeptide BPC 157, H2-blockers, omeprazole and sucralfate on new vessels and new granulation tissue formation.

PubMed

Sikiric, P; Separovic, J; Anic, T; Buljat, G; Mikus, D; Seiwerth, S; Grabarevic, Z; Stancic-Rokotov, D; Pigac, B; Hanzevacki, M; Marovic, A; Rucman, R; Petek, M; Zoricic, I; Ziger, T; Aralica, G; Konjevoda, P; Prkacin, I; Gjurasin, M; Miklic, P; Artukovic, B; Tisljar, M; Bratulic, M; Mise, S; Rotkvic, I

1999-12-01

A clear protection of the gastrointestinal tract and an evident anti-inflammatory effect were shown for a novel stomach pentadecapeptide BPC 157 (i.p./i.g.) in comparison with several reference standards in various ulcer models along with a protection of endothelium and particular interaction with the NO-system. Thus, we evaluated whether this pentadecapeptide along with other gastroprotective agents could affect angiogenesis and the healing process in vivo using a procedure initially described by Szabo and co-workers. In each rat, two sterile sponges (1 x 1 x 0.25 cm; V = 0.25 mL) with the same quantities of BPC 157 (10 ng x mL(-1), 10 microg x mL(-1), 50 microg x kg(-1)) or reference agents (cimetidine: 10, 100, 500 mg x mL(-1); ranitidine: 2.5, 25, 250 mg x mL(-1); famotidine: 10, 50, 100 mg x mL(-1); omeprazole: 10, 50, 100 mg x mL(-1); sucralfate: 1, 5, 10 mg x mL(-1) were implanted subcutaneously in the lumbar region. The sponges were removed after 3 or 7 d, fixed in formalin, and processed for histologic and histochemical evaluation and morphometry assessment. Compared with the control values, the number of newly formed endothelial spaces inside newly formed granulation tissue was markedly increased in all animals treated with BPC 157, cimetidine, ranitidine, famotidine, sucralfate and omeprazole, a consistent finding noted after either 3 or 7 d. Compared with control values, markedly more granulation tissue was noted in the rats in the groups of animals treated with BPC 157 (50 microg) and in the rats treated with sucralfate in all dosages used, euthanized after 3 d. In all groups treated with H2-blockers however, similar values to those of controls were noted. Thus, it could be concluded that an evident angiogenic property was consistently noted for the novel pentadecapeptide BPC 157, H2-blockers (cimetidine, famotidine and ranitidine) and omeprazole, besides the well known angiogenic effect of sucralfate. Furthermore, unlike H2-blockers and omeprazole

Duodenocutaneous fistula in rats as a model for "wound healing-therapy" in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine.

PubMed

Skorjanec, S; Kokot, A; Drmic, D; Radic, B; Sever, M; Klicek, R; Kolenc, D; Zenko, A; Lovric Bencic, M; Belosic Halle, Z; Situm, A; Zivanovic Posilovic, G; Masnec, S; Suran, J; Aralica, G; Seiwerth, S; Sikiric, P

2015-08-01

While very rarely reported, duodenocutanenous fistula research might alter the duodenal ulcer disease background and therapy. Our research focused on rat duodenocutaneous fistulas, therapy, stable gastric pentadecapeptide BPC 157, an anti-ulcer peptide that healed other fistulas, nitric oxide synthase-substrate L-arginine, and nitric oxide synthase-inhibitor L-nitro-arginine methyl ester (L-NAME). The hypothesis was, duodenal ulcer-healing, like the skin ulcer, using the successful BPC 157, with nitric oxide-system involvement, the "wound healing-therapy", to heal the duodenal ulcer, the fistula-model that recently highlighted gastric and skin ulcer healing. Pressure in the lower esophageal and pyloric sphincters was simultaneously assessed. Duodenocutaneous fistula-rats received BPC 157 (10 μg/kg or 10 ng/kg, intraperitoneally or perorally (in drinking water)), L-NAME (5 mg/kg intraperitoneally), L-arginine (100 mg/kg intraperitoneally) alone and/or together, throughout 21 days. Duodenocutaneous fistula-rats maintained persistent defects, continuous fistula leakage, sphincter failure, mortality rate at 40% until the 4(th) day, all fully counteracted in all BPC 157-rats. The BPC 157-rats experienced rapidly improved complete presentation (maximal volume instilled already at 7(th) day). L-NAME further aggravated the duodenocutaneous fistula-course (mortality at 70% until the 4(th) day); L-arginine was beneficial (no mortality; however, maximal volume instilled not before 21(st) day). L-NAME-worsening was counteracted to the control level with the L-arginine effect, and vice versa, while BPC 157 annulled the L-NAME effects (L-NAME + L-arginine; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157 brought below the level of the control). It is likely that duodenocutaneous fistulas, duodenal/skin defect simultaneous healing, reinstated sphincter function, are a new nitric oxide-system related phenomenon. In conclusion, resolving the duodenocutanenous fistulashealing

Prolonged esophagitis after primary dysfunction of the pyloric sphincter in the rat and therapeutic potential of the gastric pentadecapeptide BPC 157.

PubMed

Dobric, Ivan; Drvis, Petar; Petrovic, Igor; Shejbal, Drazen; Brcic, Luka; Blagaic, Alenka Boban; Batelja, Lovorka; Sever, Marko; Kokic, Neven; Tonkic, Ante; Zoricic, Ivan; Mise, Sandro; Staresinic, Mario; Radic, Bozo; Jakir, Ana; Babel, Jaksa; Ilic, Spomenko; Vuksic, Tihomir; Jelic, Ivan; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

2007-05-01

Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 microg/kg, 10 ng/kg, last application 24 h before assessment), or continuously in drinking water at 0.16 microg/ml, 0.16 ng/ml (12 ml/rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH2O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg/kg, intraperitoneally, once daily; 0.83 mg/ml in drinking water; 50 mg/kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats.

Nonsteroidal anti-inflammatory drugs-induced failure of lower esophageal and pyloric sphincter and counteraction of sphincters failure with stable gatric pentadecapeptide BPC 157 in rats.

PubMed

Vitaic, S; Stupnisek, M; Drmic, D; Bauk, L; Kokot, A; Klicek, R; Vcev, A; Luetic, K; Seiwerth, S; Sikiric, P

2017-04-01

The sphincters failure is a part of NSAIDs-toxicity that can be accordingly counteracted. We used a safe stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), LD1 not achieved, since successful in inflammatory bowel disease trials, and counteracts esophagitis, sphincters failure, gastrointestinal ulcer and skin ulcer, external and internal fistulas in rats, and particularly counteracts all NSAIDs-lesions. We assessed lower esophageal sphincter and pyloric sphincter pressure (cmH 2 O) in rats treated with various NSAIDs regimens, at corresponding time points, known to produce stomach, small intestine lesions, hepatotoxicity and encephalopathy. Assessment was after diclofenac (12.5 mg/kg, 40 mg/kg intraperitoneal challenge), ibuprofen (400 mg/day/kg intraperitoneally for 4 weeks), paracetamol (5.0 g/kg intraperitoneal challenge), aspirin (400 mg/kg intraperitoneally or intragastrically), celecoxib (0.5 mg/kg, 1.0 mg/kg intraperitoneally). BPC 157 (10 μg/kg, 10 ng/kg) was given immediately after NSAIDs (intraperitoneally or intragastrically) or given in drinking water. Regularly, in all control NSAIDs fall of pressure occurred in both sphincters rapidly and then persisted. By contrast, in all NSAIDs-rats that received BPC 157, initial fall of pressure was minimized and pressure values restored to normal values. All tested NSAIDs decrease pressure in both sphincters, whilst BPC 157 counteracts their effects and restored both sphincters function.

NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs.

PubMed

Kokot, Antonio; Zlatar, Mirna; Stupnisek, Mirjana; Drmic, Domagoj; Radic, Radivoje; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2016-01-15

We revealed an immediate and hours-lasting particular NO-specific parallel miotic effect of L-NAME and L-arginine in rats and guinea pigs and a stable gastric pentadecapeptide BPC 157 157-particular effect vs. that of atropine-induced mydriasis while examining the NO system role in the normal pupils responses and pupils with atropine-induced mydriasis. We also assessed the responses to BPC 157 and its possible modulation of the changes caused by L-NAME/L-arginine and atropine. We administered locally (two drops/eye) or systemically (intraperitoneally/kg) [BPC 157 (0.4µg/eye; 10µg, 10ng, 10pg/kg), L-NAME (0.1mg/eye; 5mg/kg), and L-arginine (2mg/eye; 100mg/kg) alone and combined] at 3min prior to assessment (normal pupils) or alternatively at maximal 1% atropine-induced mydriasis (30min after two drops were administered to each eye). L-NAME/L-arginine. Normal pupil. L-NAME-miosis and L-arginine-miosis shortened and attenuated each other's responses when combined (L-NAME+L-arginine) (except with guinea pigs treated locally) and were thereby NO-specific. Atropine-pupil. Both L-NAME and L-arginine counteracted atropine-induced mydriasis. With few exceptions, the atropine+L-NAME+L-arginine-animals showed a consistent shift toward the left. BPC 157. Normal pupil. Always, BPC 157 alone (both species; locally; systemically; all regimens) did not affect normal pupils. Despite specific exceptions, BPC 157 distinctively affects L-arginine-miosis (prolongation) and L-NAME-miosis (shortening). When L-arginine and L-NAME were combined (L-NAME+L-arginine+BPC 157), the effect was less pronounced. Atropine-pupil. BPC 157 alone counteracted atropine-induced mydriasis. With few exceptions (when administered with L-NAME or L-arginine or L-NAME+L-arginine), BPC 157 augments their counteracting effects. Thus, along with its l-NAME/L-arginine effects, BPC 157 participates in ocular control, potentially via NO-mediated and cholinergic mechanisms. Copyright © 2015 Elsevier B.V. All

Long-lasting cytoprotection after pentadecapeptide BPC 157, ranitidine, sucralfate or cholestyramine application in reflux oesophagitis in rats.

PubMed

Sikiric, P; Jadrijevic, S; Seiwerth, S; Sosa, T; Deskovic, S; Perovic, D; Aralica, G; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Ziger, T; Rotkvic, I; Mise, S; Zoricic, I; Sebecic, B; Patrlj, L; Kocman, B; Sarlija, M; Mikus, D; Separovic, J; Hanzevacki, M; Gjurasin, M; Miklic, P

1999-12-01

Recently, the effectiveness of pentadecapeptide BPC 157 and other anti-ulcer agents, called 'direct cytoprotection', was evidenced in totally gastrectomized rats duodenum challenged with cysteamine 24 h after surgery, and sacrificed 24 h after ulcerogen application. The further focus was on the possibility that this effect could be seen over a more prolonged period (1, 2, 4 weeks), and in other parts of the gastrointestinal tract (i.e. oesophagus). After the removal of the stomach, the oesophagus and jejunum were joined by a termino-lateral anastomosis. The animals were euthanized 7, 14 or 28 d after surgery, when oesophagitis was blindly assessed both macroscopically (percentage of ulcerations areas) and microscopically (percentage of areas of ulcers, regeneration and hyperplasia; number of inflammatory cells - polymorphonuclear and mononuclear). Starting 24 h after surgery, the medication was continuously given in the drinking water, in a volume of 12.5 mL/rat daily, until euthanasia at the end of the observation period, i.e. 7, 14, 28 d following surgery. Based on previous experiments, the doses of agents were daily calculated per kg b.w. as follows: BPC 157 125 mg or 125 ng, cholestyramine 2.5 mg, ranitidine 125 mg, sucralfate 725 mg, whereas controls received 72.5 mL x kg(-1) water. In support of these initial findings, and considering gastrectomized acid-free rats as an ideal model for long-term cytoprotective studies as well, pentadecapeptide BPC 157 markedly attenuated termino-lateral oesophagojejunal anastomosis-reflux oesophagitis also over a quite prolonged period. This efficacy was only partly shared by other anti-ulcer agents. After 1-week-old oesophagitis (microscopical assessment), but not after 2 or 4 weeks, less damaged mucosa was noted in rats drinking ranitidine or sucralfate compared to controls. Similar effectiveness was noted for cholestyramine. The obtained results were supported also by inflammatory cell assessment. Compared with control

Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system.

PubMed

Klicek, Robert; Sever, Marko; Radic, Bozo; Drmic, Domagoj; Kocman, Ivan; Zoricic, Ivan; Vuksic, Tihomir; Ivica, Mihovil; Barisic, Ivan; Ilic, Spomenko; Berkopic, Lidija; Vrcic, Hrvoje; Brcic, Luka; Blagaic, Alenka Boban; Coric, Marijana; Brcic, Iva; Rokotov, Dinko Stancic; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

2008-09-01

We focused on the therapeutic effect of the stable gastric pentadecapeptide BPC 157 and how its action is related to nitric oxide (NO) in persistent colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin defect of 5 mm); this peptide has been shown to be safe in clinical trials for inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy. BPC 157 (10 microg/kg, 10 ng/kg) was applied i) in drinking water until the animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii) once daily intraperitoneally (first application 30 min following surgery, last 24 h before sacrifice) alone or with N(G)-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg), L-arginine (200 mg/kg), and their combinations. Sulphasalazine (50 mg/kg) and 6-alpha-methylprednisolone (1 mg/kg) were given once daily intraperitoneally. BPC 157 accelerated parenterally or perorally the healing of colonic and skin defect, leading to the suitable closure of the fistula, macro/microscopically, biomechanically, and functionally (larger water volume sustained without fistula leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (L-NAME groups). L-Arginine was effective only with blunted NO generation (L-NAME + L-arginine groups) but not without (L-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as well as L-NAME and L-arginine co-administration (L-NAME + L-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect.

The effect of a novel pentadecapeptide BPC 157 on development of tolerance and physical dependence following repeated administration of diazepam.

PubMed

Jelovac, N; Sikiric, P; Rucman, R; Petek, M; Perovic, D; Marovic, A; Anic, T; Seiwerth, S; Mise, S; Pigac, B; Duplancie, B; Turkovic, B; Dodig, G; Prkacin, I; Stancic-Rokotov, D; Zoricic, I; Aralica, G; Sebecic, B; Ziger, T; Slobodnjak, Z

1999-09-30

A novel gastric pentadecapeptide BPC 157 with different beneficial activities and anticonvulsant effect interacting with GABAergic system could improve diazepam efficacy coadministered (10 microg/kg, 10 ng/kg i.p.) with diazepam (5.0 mg/kg i.p.) twice daily for 10 days, since diazepam chronic medication would otherwise predispose for diazepam- tolerance/withdrawal development (shorter latency to convulsion after convulsant). In diazepam chronically treated mice, it attenuated diazepam tolerance (provoked by later acute administration of diazepam together with convulsant) and postponed physical dependence/withdrawal effects (provoked by later administration of isoniazid). In tolerance assay, at 42 h after the end of conditioning regimen, shorter preconvulsive latencies than in healthy (non-diazepam conditioned) mice following isoniazid (800 mg/kg i.p.) (as hallmark of tolerance) were observed if diazepam (5.0 mg/kg i.p.) was again given acutely to mice previously conditioned with diazepam alone (use of picrotoxin 3.0 mg/kg i.p., as convulsant, with acute application of diazepam in previously diazepam conditioned mice did not lead to tolerance hallmark). This was completely avoided in diazepam+BPC 157 10 microg or diazepam+BPC 157 10 ng chronically treated animals. In physical dependence assay (isoniazid challenge assessed at 6, 14, 42 and 72 h after conditioning medication), when compared to diazepam non-conditioned healthy mice, in diazepam conditioned mice residual anticonvulsive activity was not present already at the earliest post-conditioning interval (i.e., not different latency to isoniazid-convulsions), whereas shorter preconvulsive latencies (as physical dependence/withdrawal hallmark) were noted in diazepam conditioned mice following isoniazid challenge at 42 h and at 72 h after end of conditioning treatment. In diazepam+BPC 157 10 microg- conditioned mice, a residual anticonvulsive activity (i.e., longer latency to isoniazid convulsion) was noted at 6 h

Revised Robert's cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications for novel mediator.

PubMed

Sikiric, Predrag; Seiwerth, Sven; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela

2010-01-01

The significance of cytoprotection and adaptive cytoprotection and the peptides importance remained to be not completely determined. BPC 157 is an anti-ulcer peptidergic agent, proven in clinical trials to be both safe in inflammatory bowel disease (PL-10, PLD-116, PL 14736) and wound healing, and stable in human gastric juice, with no toxicity being reported. It has a prominent effect on alcohol- lesions (i.e., induced acutely and chronically) and non-steroidal anti-inflammatory drugs-lesions (while interestingly BPC 157 may both prevent and reverse adjuvant arthritis). To review the importance of BPC 157, this review focused on Robert's cytoprotection concept described in rat stomach, reviewing our evidence that may resolve whether the cytoprotection and adaptive cytoprotection is an uniform phenomenon or not; whether the phenomenon or phenomena are endogenous or not, depending on nature of the irritants (mild or strong); whether this may contribute to stomach mucosa defense either when threaten by various ulcerogens or afforded by various antiulcer agents; whether these phenomena are uniform in whole gastrointestinal tract or not; whether they are interrelated or not. Finally, the importance of the cytoprotection phenomena and cytoprotection activity for skin wound healing, and wound healing in general was challenged. Thereby, this review focused on BPC 157 role in cytoprotection and adaptative cytoprotection suggesting that it may be the essential endogenous mediator able to mediate both cytoprotective and adaptive cytoprotective response in stomach and the whole gastrointestinal tract with significant importance in wound healing as well.

The pharmacological properties of the novel peptide BPC 157 (PL-10).

PubMed

Sikiric, P

1999-01-01

The reported beneficial effects of the gastric mucosal derived pentadecapeptide BPC 157 (Gly Glu Pro Pro Pro Gly Lys Pro Ala Asp Asp Ala Gly Leu Val, M.W. 1419) on different organ lesions are reviewed. Apart from the effects on various gastrointestinal lesions, the potentially beneficial effect on pancreas, liver injuries, endothelium and heart damage, i.e. dysrhythmias following reoxygenation, and blood pressure, along with effect on experimental acute/chronic inflammation, wound and fracture (pseudoarthrosis) healing are described. It appears that these beneficial effects all together provide a particular network reflecting activity of a special peptidergic defence system. In support of this concept, it appears that there are interactions of this pentadecapeptide with many important systems (namely, dopamine-, NO-, prostaglandin-, somatosensory neurone-systems), that could provide a basis for the observed protective effects. Moreover, since disturbance of these systems' functions (i.e. dopamine-, NO-, somatosensory neuronal-system) which manifest either over-activity or as inhibition, may contribute to the multiple lesions in different organs. The reported evidence that this pentadecapeptide is able to counteract both their over-action, and their inhibition, may suggest this pentadecapeptide as a new, but most probably essential physiological defence system and that should be further investigated.

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

PubMed Central

Djakovic, Zeljko; Djakovic, Ivka; Cesarec, Vedran; Madzarac, Goran; Becejac, Tomislav; Zukanovic, Goran; Drmic, Domagoj; Batelja, Lovorka; Zenko Sever, Anita; Kolenc, Danijela; Pajtak, Alen; Knez, Nikica; Japjec, Mladen; Luetic, Kresimir; Stancic-Rokotov, Dinko; Seiwerth, Sven; Sikiric, Predrag

2016-01-01

AIM To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. METHODS Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 μg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation. RESULTS BPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning (i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME.

PubMed

Djakovic, Zeljko; Djakovic, Ivka; Cesarec, Vedran; Madzarac, Goran; Becejac, Tomislav; Zukanovic, Goran; Drmic, Domagoj; Batelja, Lovorka; Zenko Sever, Anita; Kolenc, Danijela; Pajtak, Alen; Knez, Nikica; Japjec, Mladen; Luetic, Kresimir; Stancic-Rokotov, Dinko; Seiwerth, Sven; Sikiric, Predrag

2016-11-07

To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 μg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H 2 O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H 2 O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation. BPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning ( i.e ., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine); with

Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME

PubMed Central

Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag

2017-01-01

AIM To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODS Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTS This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSION BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement. PMID:28839430

Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME.

PubMed

Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag

2017-08-07

To counteract/reveal celecoxib-induced toxicity and NO system involvement. Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs' post-surgery application and NO system involvement.

The antidepressant effect of an antiulcer pentadecapeptide BPC 157 in Porsolt's test and chronic unpredictable stress in rats. A comparison with antidepressants.

PubMed

Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Marovic, A; Prkacin, I; Duplancic, B; Zoricic, I; Aralica, G; Lovric-Bencic, M; Ziger, T; Perovic, D; Rotkvic, I; Mise, S; Hanzevacki, M; Hahn, V; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R

2000-01-01

Various antidepressants have antiulcer activity. Likewise, the models currently used in ulcers and depression disorders research have a considerable degree of similarity. Therefore, the possibility that depression disorders could be effectively influenced by a primary antiulcer agent with a cyto/organoprotective activity, such as the novel stomach pentadecapeptide BPC 157, was investigated in two rat depression assays. First, a forced swimming test (a Porsolt's procedure) was used. As a more severe procedure, chronic unpredictable stress (after 5 d of unpredictable stress protocol, once daily drug application during stress procedure, open field-immobility test assessment at fourth or sixth day of medication) was used. In a forced swimming test, a reduction of the immobility time in BPC 157 (10 microg, 10 ng x kg(-1) i.p.) treated rats corresponds to the activity of the 15 mg or 40 mg (i.p.) of conventional antidepressants, imipramine or nialamide, respectively, given according to the original Porsolt's protocol. In chronic unpredictable stress procedure, particular aggravation of experimental conditions markedly affected the conventional antidepressant activity, whereas BPC 157 effectiveness was continuously present. The effect of daily imipramine (30 mg) medication could be seen only after a more prolonged period, but not after a shorter period (i.e., 4-d protocol). In these conditions, no delay in the effectiveness was noted in BPC 157 medication and a reduction of the immobility of chronically stressed rats was noted after both 4 and 6 d of BPC 157 (10 microg, 10 ng) medication.

Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.

PubMed

Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

2016-01-01

Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats

PubMed Central

Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

2016-01-01

Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

PubMed

Belosic Halle, Zeljka; Vlainic, Josipa; Drmic, Domagoj; Strinic, Dean; Luetic, Kresimir; Sucic, Mario; Medvidovic-Grubisic, Maria; Pavelic Turudic, Tatjana; Petrovic, Igor; Seiwerth, Sven; Sikiric, Predrag

2017-05-17

The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H 2 O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased

Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157.

PubMed

Vukojević, Jakša; Siroglavić, Marko; Kašnik, Katarina; Kralj, Tamara; Stanćić, Duje; Kokot, Antonio; Kolarić, Darko; Drmić, Domagoj; Sever, Anita Zenko; Barišić, Ivan; Šuran, Jelena; Bojić, Davor; Patrlj, Masa Hrelec; Sjekavica, Ivica; Pavlov, Katarina Horvat; Vidović, Tinka; Vlainić, Josipa; Stupnišek, Mirjana; Seiwerth, Sven; Sikirić, Predrag

2018-03-03

Rat inferior caval vein (ICV) ligation (up to the right ovarian vein (ROV)) commonly represents a recapitulation of Virchow: with ligation leading to vessel injury, stasis, thrombosis and hemodynamic changes. We revealed that BPC 157's therapy collectively attenuated or counteracted all these events and the full syndrome. We applied BPC 157 (10 μg, 10 ng/kg) as an early regimen or as a delayed therapy. Assessment includes gross assessment by microcamera; microscopy, venography, bleeding, blood pressure, ECG, thermography, MDA and NO-level in plasma and ICV, and gene expression. Direct vein injury, thrombosis, thrombocytopenia, prolonged bleeding were all counteracted. Also, rapid presentation of collaterals and redistribution of otherwise trapped blood volume (bypassing through the left ovarian vein (LOV) and other veins), with venous hypertension, arterial hypotension and tachycardia counteraction were shown. BPC 157-rats presented raised plasma NO-values, but normal MDA-values; in ICV tissue reverted low NO-values and counteracted increased MDA-levels. Altered expression of EGR, NOS, SRF, VEGFR and KRAS in ICV, ROV and LOV revealed increased or decreased levels, while some genes continuously remained unchanged. As a new insight, BPC 157 application largely attenuated or even completely eliminated all consequences of ICV ligation in rats. Copyright © 2018 Elsevier Inc. All rights reserved.

BPC 157 antagonized the general anaesthetic potency of thiopental and reduced prolongation of anaesthesia induced by L-NAME/thiopental combination.

PubMed

Zemba, Mladen; Cilic, Andrea Zemba; Balenovic, Igor; Cilic, Matija; Radic, Bozo; Suran, Jelena; Drmic, Domagoj; Kokot, Antonio; Stambolija, Vasilije; Murselovic, Tamara; Holjevac, Jadranka Katancic; Uzun, Sandra; Djuzel, Viktor; Vlainic, Josipa; Seiwerth, Sven; Sikiric, Predrag

2015-12-01

We hypothesized that certain effects of the general anaesthetic thiopental are dependent on NO-related mechanisms, which were consequently counteracted by stable gastric pentadecapeptide BPC 157. (1) All rats intraperitoneally received thiopental (20, 30, 40, and 50 mg/kg) while medication BPC 157 (10 μg/kg, 10 ng/kg, and 10 pg/kg) was given intraperitoneally at 5 min before thiopental. (2) To determine NO-related mechanisms, all rats received intraperitoneally thiopental 40 mg/kg while BPC 157 (10 μg/kg), L-NAME (10 mg/kg) and L-arginine (30 mg/kg) were applied alone and/or combined. BPC 157 was given at 25 min before thiopental while L-NAME, L-arginine, alone and/or combined, were applied at 20 min before thiopental. (1) BPC 157 own effect on thiopental anaesthesia: BPC 157 (10 ng/kg and 10 μg/kg) caused a significant antagonism of general anaesthesia produced by thiopental with a parallel shift of the dose-response curve to the right. (2) L-NAME-L-arginine-BPC 157 interrelations: L-NAME: Thiopental-induced anaesthesia duration was tripled. L-arginine: Usual thiopental anaesthesia time was not influenced. Active only when given with L-NAME or BPC 157: potentiating effects of L-NAME were lessened, not abolished; shortening effect of BPC 157: abolished. BPC 157 and L-NAME: Potentiating effects of L-NAME were abolished. BPC 157 and L-NAME and L-arginine: BPC 157 +L-NAME +L-arginine rats exhibited values close to those in BPC 157 rats. Thiopental general anaesthesia is simultaneously manipulated in both ways with NO system activity modulation, L-NAME (prolongation) and BPC 157 (shortening/counteraction) and L-arginine (interference with L-NAME and BPC 157).

Antiinflammatory effect of BPC 157 on experimental periodontitis in rats.

PubMed

Keremi, B; Lohinai, Z; Komora, P; Duhaj, S; Borsi, K; Jobbagy-Ovari, G; Kallo, K; Szekely, A D; Fazekas, A; Dobo-Nagy, C; Sikiric, P; Varga, G

2009-12-01

The pentadecapeptide BPC 157 has been shown to have anti-inflammatory and wound healing effects on multiple target tissues and organs. The purpose of the present study was to investigate the effect of BPC 157 on inflammation and bone resorption in experimental periodontitis in rats. First the acute effect of BPC was tested on gingival blood flow by laser doppler flowmetry. Then periodontitis was produced by a silk ligature placed around the lower left first molar. Rats were treated with BPC 157 (once daily for 12 days) or vehicle. At day 13, the gingivomucosal tissues encircling the molars were removed on both sides. Inflammation was assessed by Evans blue plasma extravasation technique and by histology. Alveolar bone loss was analyzed by microCT. BPC 157 had no effect on gingivomucosal blood flow. Twelve day ligature caused a significantly increased Evans blue extravasation in the gingivomucosal tissue, histological signs of inflammation, and alveolar bone destruction. BPC 157 treatment significantly reduced both plasma extravasation, histological alterations and alveolar bone resorption. In conclusion, systemic application of BPC 157 does not alter blood circulation in healthy gingiva. Chronic application of the peptide has potent antiinflammatory effects on periodontal tissues in ligature induced periodontitis in rats. Taken together, this proof of concept study suggests that BPC 157 may represent a new peptide candidate in the treatment of periodontal disease.

BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias.

PubMed

Stambolija, Vasilije; Stambolija, Tamara Perleta; Holjevac, Jadranka Katancic; Murselovic, Tamara; Radonic, Jelena; Duzel, Viktor; Duplancic, Bozidar; Uzun, Sandra; Zivanovic-Posilovic, Gordana; Kolenc, Danijela; Drmic, Domagoj; Romic, Zeljko; Seiwerth, Sven; Sikiric, Predrag

2016-06-15

After the demonstration of its life-saving effect in severe hyperkalemia and the recovery of skeletal muscle after injury, pentadecapeptide BPC 157 has been shown to attenuate the local paralytic effect induced by succinylcholine, in addition to systemic muscle disability (and consequent muscle damage). Hyperkalemia, arrhythmias and a rise in serum enzyme values, were counteracted in rats. Assessments were made at 3 and 30min and 1, 3, 5, and 7 days after succinylcholine administration (1.0mg/kg into the right anterior tibial muscle). BPC 157 (10µg/kg, 10ng/kg) (given intraperitoneally 30min before or immediately after succinylcholine or per-orally in drinking water through 24h until succinylcholine administration) mitigated both local and systemic disturbances. BPC 157 completely eliminated hyperkalemia and arrhythmias, markedly attenuated or erradicated behavioral agitation, muscle twitches, motionless resting and completely eliminated post-succinylcholine hyperalgesia. BPC 157 immediately eliminated leg contractures and counteracted both edema and the decrease in muscle fibers in the diaphragm and injected/non-injected anterior tibial muscles. Therefore, the depolarizing neuromuscular blocker effects of succinylcholine were successfully antagonized. Copyright © 2016 Elsevier B.V. All rights reserved.

Therapeutic potential of pro-angiogenic BPC157 is associated with VEGFR2 activation and up-regulation.

PubMed

Hsieh, Ming-Jer; Liu, Hsien-Ta; Wang, Chao-Nin; Huang, Hsiu-Yun; Lin, Yuling; Ko, Yu-Shien; Wang, Jong-Shyan; Chang, Vincent Hung-Shu; Pang, Jong-Hwei S

2017-03-01

BPC 157, a pentadecapeptide with extensive healing effects, has recently been suggested to contribute to angiogenesis. However, the underlying mechanism is not yet clear. The present study aimed to explore the potential therapeutic effect and pro-angiogenic mechanism of BPC 157. As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively. BPC 157 could also accelerate the recovery of blood flow in the ischemic muscle of the rat hind limb as detected by laser Doppler scanning, indicating the promotion of angiogenesis. Histological analysis of the hind limb muscle confirmed the increased number of vessels and the enhanced vascular expression of vascular endothelial growth factor receptor 2 (VEGFR2) in rat with BPC 157 treatment. In vitro study using human vascular endothelial cells further confirmed the increased mRNA and protein expressions of VEGFR2 but not VEGF-A by BPC 157. In addition, BPC 157 could promote VEGFR2 internalization in vascular endothelial cells which was blocked in the presence of dynasore, an inhibitor of endocytosis. BPC 157 time dependently activated the VEGFR2-Akt-eNOS signaling pathway which could also be suppressed by dynasore. The increase of endothelial tube formation induced by BPC 157 was also inhibited by dynasore. This study demonstrates the pro-angiogenic effects of BPC 157 that is associated with the increased expression, internalization of VEGFR2, and the activation of VEGFR2-Akt-eNOS signaling pathway. BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation. BPC 157 promotes angiogenesis in CAM assay and tube

Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157.

PubMed

Luetic, Krešimir; Sucic, Mario; Vlainic, Josipa; Halle, Zeljka Belosic; Strinic, Dean; Vidovic, Tinka; Luetic, Franka; Marusic, Marinko; Gulic, Sasa; Pavelic, Tatjana Turudic; Kokot, Antonio; Seiwerth, Ranka Serventi; Drmic, Domagoj; Batelja, Lovorka; Seiwerth, Sven; Sikiric, Predrag

2017-04-01

We revealed a new point with cyclophosphamide (150 mg/kg/day intraperitoneally for 7 days): we counteracted both rat stomach and duodenal ulcers and increased NO- and MDA-levels in these tissues. As a NO-system effect, BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once a day or in drinking water, till the sacrifice) attenuated the increased NO- and MDA-levels and nullified, in rats, severe cyclophosphamide-ulcers and even stronger stomach and duodenal lesions after cyclophosphamide + L-NAME (5 mg/kg intraperitoneally once a day). L-arginine (100 mg/kg intraperitoneally once a day not effective alone) led L-NAME-values only to the control values (cyclophosphamide + L-NAME + L-arginine-rats). Briefly, rats were sacrificed at 24 h after last administration on days 1, 2, 3, or 7, and assessment included sum of longest lesions diameters (mm) in the stomach and duodenum, oxidative stress by quantifying thiobarbituric acid reactivity as malondialdehyde equivalents (MDA), NO in stomach and duodenal tissue samples using the Griess reaction. All these parameters were highly exaggerated in rats who underwent cyclophosphamide treatment. We identified high MDA-tissue values, high NO-tissue values, ulcerogenic and beneficial potential in cyclophosphamide-L-NAME-L-arginine-BPC 157 relationships. This suggests that in cyclophosphamide damaged rats, NO excessive release generated by the inducible isozyme, damages the vascular wall and other tissue cells, especially in combination with reactive oxygen intermediates, while failing endothelial production and resulting in further aggravation by L-NAME which was inhibited by L-arginine. Finally, BPC 157, due to its special relations with NO-system, may both lessen increased MDA- and NO-tissues values and counteract effects of both cyclophosphamide and L-NAME on stomach and duodenal lesions.

The influence of BPC 157 on nitric oxide agonist and antagonist induced lesions in broiler chicks.

PubMed

Grabarevic, Z; Tisljar, M; Artukovic, B; Bratulic, M; Dzaja, P; Seiwerth, S; Sikiric, P; Peric, J; Geres, D; Kos, J

1997-01-01

We describe the effects of nitric oxide (NO) agonists and antagonists and the influence of a novel organoprotective pentadecapeptide BPC 157, on the development of pulmonary hypertension syndrome and tissue lesions in chicks. Acute toxicity, which includes single dose application of saline (1 mL intraperitoneally (i.p.)), BPC 157 (10 micrograms/kg bw), L-NAME (NO antagonist, doses 50, 100, 150 mg/kg bw) and L-arginine (NO agonist/100 mg/kg bw with their combination L-NAME + BPC 157; L-NAME + L-arginine) was investigated. In this experiment pathohistological examination of the spleen, heart, liver and lungs and hematological analysis was conducted. In the chronic toxicity experiment, the animals were treated daily for 5 weeks with L-NAME (10 mg/kg bw), L-arginine (100 mg/kg bw), BPC 157 (10 micrograms/kg bw) and their combinations (L-NAME + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine) i.p. Seven animals from each group, including controls (saline 1 mL i.p.) were killed every week. Application of L-NAME caused pulmonary hypertension syndrome (PHS) in the treated chicks, which was prevented by the simultaneous application of L-arginine and BPC 157. Pathohistological examination of both acute and chronic toxicity revealed that L-NAME caused severe tissue damage (myocardial and hepatic cell necrosis, necrosis of the lymphoid cells in the spleen) while L-arginine provoked predominantly congestion, edema and hemorrhages in all organs. The effect of L-NAME was successfully inhibited by the application of L-arginine and BPC 157 but the latter substance did not cause any tissue or organ damage. Hematological analysis shows significant hemoglobin and leukocyte number decrease in the L-NAME-treated groups of chicks.

Pentadecapeptide BPC 157 and anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration.

PubMed

Duplancic, Bozidar; Stambolija, Vasilije; Holjevac, Jadranka; Zemba, Mladen; Balenovic, Igor; Drmic, Domagoj; Suran, Jelena; Radic, Bozo; Filipovic, Marinko; Blagaic, Alenka Boban; Brcic, Luka; Kolenc, Danijela; Grabarevic, Zeljko; Seiwerth, Sven; Sikiric, Predrag

2014-03-15

Anesthetized mice or rats received intravenously 6%, 10%, 20%, 40%, 60%, 80%, and 90% dextran and/or white egg (1ml/rat or 0.15ml/mouse) into their tails. Medication (/kg b.w., 5ml/kg) was given intraperitoneally (BPC 157 10µg, 1µg, 10ng, and 10pg/kg, chloropyramine 20mg/kg, and cimetidine 10mg/kg intraperitoneally, alone or in combination while controls received an equivolume of saline), immediately after challenge or, alternatively, at 5min after or 24 or 48h before challenge. The effect was assessed at 5, 10, 20 and 30min after dextran and/or white egg challenge. We commonly noted prominent edema involving the face, upper and lower lip, snout, paws and scrotum (presented with extreme cyanosis), poor respiration and the number of fatalities after dextran and/or white egg application. Contrary, BPC 157 regimens (10µg, 1µg, 10ng, and 10pg/kg) effectively, may both prevent anaphylactoid reactions that may arise from dextran and/or white egg application and furthermore, rescue already advanced reactions when given after the challenge. Chloropyramine and cimetidine given alone were only moderately effective. When given together with BPC 157, the observed effect correlates with the strong effect of BPC 157 given alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Rational Design of Cyclic Antimicrobial Peptides Based on BPC194 and BPC198.

PubMed

Cirac, Anna D; Torné, Maria; Badosa, Esther; Montesinos, Emilio; Salvador, Pedro; Feliu, Lidia; Planas, Marta

2017-06-24

A strategy for the design of antimicrobial cyclic peptides derived from the lead compounds c(KKLKKFKKLQ) ( BPC194 ) and c(KLKKKFKKLQ) ( BPC198 ) is reported. First, the secondary β-structure of BPC194 and BPC198 was analyzed by carrying out molecular dynamics (MD) simulations. Then, based on the sequence pattern and the β-structure of BPC194 or BPC198 , fifteen analogues were designed and synthesized on solid-phase. The best peptides ( BPC490 , BPC918, and BPC924 ) showed minimum inhibitory concentration (MIC) values <6.2 μM against Pseudomonas syringae pv. syringae and Xanthomonas axonopodis pv. vesicatoria , and an MIC value of 12.5 to 25 μM against Erwinia amylovora , being as active as BPC194 and BPC198 . Interestingly, these three analogues followed the structural pattern defined from the MD simulations of the parent peptides. Thus, BPC490 maintained the parallel alignment of the hydrophilic pairs K¹-K⁸, K²-K⁷, and K⁴-K⁵, whereas BPC918 and BPC924 included the two hydrophilic interactions K³-Q 10 and K⁵-K⁸. In short, MD simulations have proved to be very useful for ascertaining the structural features of cyclic peptides that are crucial for their biological activity. Such approaches could be further employed for the development of new antibacterial cyclic peptides.

BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure.

PubMed

Petrovic, I; Dobric, I; Drmic, D; Sever, M; Klicek, R; Radic, B; Brcic, L; Kolenc, D; Zlatar, M; Kunjko, K; Jurcic, D; Martinac, M; Rasic, Z; Boban Blagaic, A; Romic, Z; Seiwerth, S; Sikiric, P

2011-10-01

Possibly, acute esophagitis and pancreatitis cause each other, and we focused on sphincteric failure as the common causative key able to induce either esophagitis and acute pancreatitis or both of them, and thereby investigate the presence of a common therapy nominator. This may be an anti-ulcer pentadecapeptide BPC 157 (tested for inflammatory bowel disease, wound treatment) affecting esophagitis, lower esophageal and pyloric sphincters failure and acute pancreatitis (10 μg/kg, 10 ng/kg intraperitoneally or in drinking water). The esophagitis-sphincter failure procedure (i.e., insertion of the tubes into the sphincters, lower esophageal and pyloric) and acute pancreatitis procedure (i.e., bile duct ligation) were combined in rats. Esophageal manometry was done in acute pancreatitis patients. In rats acute pancreatitis procedure produced also esophagitis and both sphincter failure, decreased pressure 24 h post-surgery. Furthermore, bile duct ligation alone immediately declines the pressure in both sphincters. Vice versa, the esophagitis-sphincter failure procedure alone produced acute pancreatitis. What's more, these lesions (esophagitis, sphincter failure, acute pancreatitis when combined) aggravate each other (tubes into sphincters and ligated bile duct). Counteraction occurred by BPC 157 therapies. In acute pancreatitis patients lower pressure at rest was in both esophageal sphincters in acute pancreatitis patients. We conclude that BPC 157 could cure esophagitis/sphincter/acute pancreatitis healing failure.

BPC 157's effect on healing.

PubMed

Seiwerth, S; Sikiric, P; Grabarevic, Z; Zoricic, I; Hanzevacki, M; Ljubanovic, D; Coric, V; Konjevoda, P; Petek, M; Rucman, R; Turkovic, B; Perovic, D; Mikus, D; Jandrijevic, S; Medvidovic, M; Tadic, T; Romac, B; Kos, J; Peric, J; Kolega, Z

1997-01-01

The 15 amino acid agent BPC 157, showing a wide range of organoprotective action in different experimental models, was used in our experiments in order to establish its influence on different elements connected with the healing process. Elements thought to be of greatest importance in the process of healing are formation of granulation tissue, angiogenesis and production of collagen. In our work we tested the influence of BPC 157 on: granulation tissue and collagen formation, on angiogenesis as well as on tensile strength development, using three experimental rat models: 1) skin incisional wounds; 2) colon-colon anastomoses; and 3) angiogenesis model with synthetic sponge implantation. The specimens were histologically assessed for collagen, reticulin and blood vessels using scoring and morphometry. In all experiments significant differences between BPC 157-treated animals and controls were found, showing a strong, promoting involvement of BPC in the healing process. It is worth noting that these effects were achieved by different routes of application, including intragastric and local, making BPC 157 a potentially useful therapeutic agent.

Detection and in vitro metabolism of the confiscated peptides BPC 157 and MGF R23H.

PubMed

Cox, Holly D; Miller, Geoff D; Eichner, Daniel

2017-10-01

A new peptide, body protecting compound (BPC), BPC 157, and a variant of mechano-growth factor (MGF), MGF R23H, were identified in confiscated vials. BPC 157 has the amino acid sequence, GEPPPGKPADDAGLV, and is currently under investigation for the promotion of healing and recovery in a variety of tissues. In vitro metabolism experiments in plasma demonstrate that MGF R23H has good stability and should be detectable in urine, while BPC 157 forms a stable metabolite that should be detectable in urine. A weak cation exchange solid phase extraction method was validated for detection of BPC 157 in urine. The method has a limit of detection of 0.1 ng/mL, precision of less than 20%, and good linearity, r 2 0.998. BPC 157 was stable in urine for at least 4 days. The specificity of the method is improved by measurement of a potential BPC metabolite along with the parent peptide. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Dose-dependent protective effect of BPC 157 on capsaicin-induced rhinitis in rats.

PubMed

Kalogjera, L; Ries, M; Baudoin, T; Ferencic, Z; Trotic, R; Pegan, B

1997-01-01

Protection of BPC 157 on capsaicin-induced rhinitis was studied in Wistar rats for its effect on mastocyte infiltration, degranulation and inflammatory cell infiltration. Animals were pretreated with 10 microg/kg, 10 ng/kg or 2 ml saline i.p. and capsaicin (0.05 ml/nostril of 1750 nmol/l sol.) was applied intranasally. They were then euthanized at 1, 3 and 12 h after capsaicin provocation. Nasal mucosa was analyzed and scored for mastocyte infiltration, degranulation and inflammatory cell infiltration. BPC 157 pretreatment significantly prevented mastocyte infiltration at 1 h. Polymorphonuclear leukocyte infiltration was significantly reduced in rats pretreated with 10 microg/kg BPC 157. A dose-dependent effect of BPC 157 pretreatment was demonstrated only for polymorphonuclear leukocyte infiltration at 12 h.

Current BPC3 Research Plan

Cancer.gov

This will expand the BPC3 to serve as a rapid verification test set for SNPs identified in the scans other than the CGEMS scan, and to examine gene-environment interactions in the SNPs identified in CGEMS and other studies as being associated with breast and prostate cancer.

BPC 157 and blood vessels.

PubMed

Seiwerth, Sven; Brcic, Luka; Vuletic, Lovorka Batelja; Kolenc, Danijela; Aralica, Gorana; Misic, Marija; Zenko, Anita; Drmic, Domagoj; Rucman, Rudolf; Sikiric, Predrag

2014-01-01

This review focuses on the described effects of BPC 157 on blood vessels after different types of damage, and elucidate by investigating different aspects of vascular response to injury (endothelium damage, clotting, thrombosis, vasoconstriction, vasodilatation, vasculoneogenesis and edema formation) especially in connection to the healing processes. In this respect, BPC 157 was concluded to be the most potent angiomodulatory agent, acting through different vasoactive pathways and systems (e.g. NO, VEGF, FAK) and leading to optimization of the vascular response followed, as it has to be expected, by optimization of the healing process. Formation of new blood vessels involves two main, partly overlapping mechanisms, angiogenesis and vasculogenesis. The additional mechanism of arteriogenesis is involved in the formation of collaterals. In conjunction with blood vessel function, we at least have to consider leakage of fluid/proteins/plasma, resulting in edema/exudate formation as well as thrombogenesis. Blood vessels are also strongly involved in tumor biology. In this aspect, we have neoangiogenesis resulting in pathological vascularization, vascular invasion resulting in release of metastatic cells and the phenomenon of homing resulting in formation of secondary tumors--metastases.

Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone.

PubMed

Krivic, A; Majerovic, M; Jelic, I; Seiwerth, S; Sikiric, P

2008-05-01

In the presented study we compared the effect of stable peptide BPC 157 and methylprednisolone on early functional recovery after Achilles tendon to bone transection in a rat model before collagen healing started. Surgical transection of the right Achilles tendon to bone area was performed in seventy two Wistar Albino male rats. Healing Achilles tendon edges were harvested at days 1-4 following the transection. Using Achilles functional index (AFI), myeloperoxidase activity, histological inflammatory cell influx and vascular index early functional recovery was evaluated. Agents (stable peptide BPC 157 10 microg methylprednisolone 5 mg, normal saline 5 ml) were given alone (/kg b.w., intraperitoneally, once daily, first 30 min after surgery, last 24 h before analysis). Control group received normal saline 5 ml/kg. BPC 157 improved functional recovery (AFI values increased at all time points, p <0.05) by anti-inflammatory (decreased myeloperoxidase (MPO) activity and histological inflammatory cell influx, p <0.05) and increased new blood vessel formation (increased vascular index, p <0.05). Methyprednisolone decreased MPO activity and histological inflammatory cell influx, (p <0.05) but also decreased new blood vessel formation and did not affect early functional recovery. Stable peptide BPC 157 with combined anti-inflammatory action and induction of early new blood vessel formation facilitates early functional recovery in Achilles tendon to bone healing.

TSCA Work Plan Chemical Technical Supplement – Physicochemical Properties and Environmental Fate of the Brominated Phthalates Cluster (BPC) Chemicals

EPA Pesticide Factsheets

TSCA Work Plan Chemical Technical Supplement – Physicochemical Properties and Environmental Fate of the Brominated Phthalates Cluster (BPC) Chemicals -- Brominated Phthalates Cluster Flame Retardants.

Individual and mixture endocrine activity of BPS and BPC using in vitro estrogenic/anti-androgenic transcriptional activation assays and the in vivo uterotrophic assay- RAP 2.2-SSWR

EPA Science Inventory

Bisphenol A (BPA) is gradually being phased out of many consumer products and processes leading to potential increases in human and environmental exposures to relatively understudied replacement compounds, including Bisphenol S (BPS) and Bisphenol C (BPC).Research from our lab ha...

[Comparison of CT findings between gastric cancer and gastric lymphoma].

PubMed

Fan, Wei-Jun; Lu, Yan-Chun; Liu, Li-Zhi; Shen, Jing-Xian; Xie, Chuan-Miao; Li, Xian; Zhang, Liang

2008-05-01

It is difficult to discriminate progressive gastric cancer and gastric lymphoma by CT imaging, because incrassate gastric wall, lump in gastric cavity, confined gastric cavity, intumescent lymph node, and distant metastasis can be displayed in both of them. This study was to compare the CT findings between gastric cancer and gastric lymphoma to improve diagnosis of gastric tumors, especially for gastric lymphoma. CT images of 27 patients with pathologically proved progressive gastric cancer and 25 patients with pathologically proved gastric lymphoma were reviewed. Tumor location, appearance, scope of involvement, gastric wall thickness, mucous membrane, mucosal fold, serosa membrane, necrosis, enhancement degree and uniformity, involvement of other organs, and abdominal lymph nodes were observed. White line sign was observed in 23 cases (85.2%) of gastric cancer, but not in the 25 cases of gastric lymphoma. The extent of white line sign in gastric cancers was larger in portal vein phase than in arterial phase. Enhancement degree outside the white line was higher in portal vein phase than in arterial phase in 13 cases (48.1%) of gastric cancer. The extent of involved gastric wall was smaller than 50% of the whole gastric wall in all the 27 cases of gastric cancer, while it was larger than 75% in 23 cases (85.2%) of gastric lymphoma. Gastric mucous membrane ulcer was found in all of the 27 cases (100%) of gastric cancer, while it was found in only 1 case (4.0%) of gastric lymphoma. Intumescent lymph nodes in two or more areas were found in 11 cases (40.0%) of gastric lymphoma, but not in gastric cancer. Intumescent lymph nodes in the retroperitoneal space below renal hilum were found in 8 cases (32%) of gastric lymphoma, but not in gastric cancer. There are some different CT features between gastric cancer and gastric lymphoma, such as white line sign, gastric mucous membrane ulcer, extent of involved gastric wall, location of intumescent lymph nodes surrounding the

Gastric infarction following gastric bypass surgery

PubMed Central

Do, Patrick H; Kang, Young S; Cahill, Peter

2016-01-01

Gastric infarction is an extremely rare occurrence owing to the stomach’s extensive vascular supply. We report an unusual case of gastric infarction following gastric bypass surgery. We describe the imaging findings and discuss possible causes of this condition. PMID:27200168

Gastric Necrosis due to Acute Massive Gastric Dilatation.

PubMed

Aydin, Ibrahim; Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

2013-01-01

Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature.

Gastric Necrosis due to Acute Massive Gastric Dilatation

PubMed Central

Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

2013-01-01

Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature. PMID:23983714

Gastric distention exacerbates ischemia in a rodent model of partial gastric devascularization.

PubMed

Urschel, J D; Antkowiak, J G; Takita, H

1997-11-01

Occult ischemia of the mobilized gastric fundus is an important etiologic factor for esophagogastric anastomotic leaks after esophagectomy. Postoperative gastric distention is another possible predisposing factor for anastomotic leakage. We hypothesized that gastric distention could worsen gastric ischemia. To test this hypothesis, gastric tissue perfusion was studied in 20 Sprague-Dawley rats. Baseline serosal gastric tissue perfusion was measured by laser-Doppler flowmetry at a point 10 mm distal to the gastroesophageal junction. Perfusion was measured after left gastric artery occlusion, gastric distention to 20 cm water pressure, and combined left gastric artery occlusion and gastric distention. Gastric tissue perfusion (in tissue perfusion units, TPU) was 64.2 +/- 9.1 TPU at baseline measurement, 18.6 +/- 4.3 TPU after left gastric artery occlusion, 22.0 +/- 4.1 TPU after gastric distention, and 7.8 +/- 1.8 TPU after combined left gastric artery occlusion and gastric distention. Distention (P < 0.0001) and arterial occlusion (P < 0.0001) both reduced gastric tissue perfusion; of the two, arterial occlusion produced the greatest reduction in perfusion (P < 0.021). The combination of distention and arterial occlusion caused greater reduction in gastric perfusion than either factor alone (P < 0.0001). In this model, gastric distention exacerbated the ischemia produced by partial gastric devascularization. In clinical esophageal surgery, postoperative gastric distention may similarly potentiate the ischemic effects of gastric transposition for esophageal reconstruction.

Laparoscopic gastric banding

MedlinePlus

... adjustable gastric banding; Bariatric surgery - laparoscopic gastric banding; Obesity - gastric banding; Weight loss - gastric banding ... gastric banding is not a "quick fix" for obesity. It will greatly change your lifestyle. You must ...

Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma.

PubMed Central

Griffiths, A P; Wyatt, J; Jack, A S; Dixon, M F

1994-01-01

A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions. Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%). This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma. PMID:7876391

Gastric volvulus with partial and complete gastric necrosis

PubMed Central

Shukla, Ram Mohan; Mandal, Kartik Chandra; Maitra, Sujay; Ray, Amit; Sarkar, Ruchirendu; Mukhopadhyay, Biswanath; Bhattacharya, Malay

2014-01-01

Here, we report two interesting cases of gastric necrosis in acute gastric volvulus due to eventration of the diaphragm. Both the cases presented with a significant challenge and were managed successfully. The management of the cases is presented and relevant literature is discussed. To the best of our knowledge, this is the first case report of gastric volvulus with gastric necrosis requiring complete and partial gastrectomy in the available English literature. PMID:24604987

Effects of gastric pacing on gastric emptying and plasma motilin

PubMed Central

Yang, Min; Fang, Dian-Chun; Li, Qian-Wei; Sun, Nian-Xu; Long, Qing-Lin; Sui, Jian-Feng; Gan, Lu

2004-01-01

AIM: To investigate the effects of gastric pacing on gastric emptying and plasma motilin level in a canine model of gastric motility disorders and the correlation between gastric emptying and plasma motilin level. METHODS: Ten healthy Mongrel dogs were divided into: experimental group of six dogs and control group of four dogs. A model of gastric motility disorders was established in the experimental group undergone truncal vagotomy combined with injection of glucagon. Gastric half-emptying time (GEt1/2) was monitored with single photon emission computerized tomography (SPECT), and the half-solid test meal was labeled with an isotope 99mTc sulfur colloid. Plasma motilin concentration was measured with radioimmunoassay (RIA) kit. Surface gastric pacing at 1.1-1.2 times the intrinsic slow-wave frequency and a superimposed series of high frequency pulses (10-30 Hz) was performed for 45 min daily for a month in conscious dogs. RESULTS: After surgery, GEt1/2 in dogs undergone truncal vagotomy was increased significantly from 56.35 ± 2.99 min to 79.42 ± 1.91 min (P < 0.001), but surface gastric pacing markedly accelerated gastric emptying and significantly decreased GEt1/2 to 64.94 ± 1.75 min (P < 0.001) in animals undergone vagotomy. There was a significant increase of plasma level of motilin at the phase of IMCIII (interdigestive myoelectrical complex, IMCIII) in the dogs undergone bilateral truncal vagotomy (baseline vs vagotomy, 184.29 ± 9.81 pg/ml vs 242.09 ± 17.22 pg/ml; P < 0.01). But plasma motilin concentration (212.55 ± 11.20 pg/ml; P < 0.02) was decreased significantly after a long-term treatment with gastric pacing. Before gastric pacing, GEt1/2 and plasma motilin concentration of the dogs undergone vagotomy showed a positive correlation (r = 0.867, P < 0.01), but after a long-term gastric pacing, GEt1/2 and motilin level showed a negative correlation (r = -0.733, P < 0.04). CONCLUSION: Surface gastric pacing with optimal pacing parameters can improve

Prolapsing Gastric Polyp Causing Intermittent Gastric Outlet Obstruction.

PubMed

Kosai, Nik Ritza; Gendeh, Hardip Singh; Norfaezan, Abdul Rashid; Razman, Jamin; Sutton, Paul Anthony; Das, Srijit

2015-06-01

Gastric polyps are often an incidental finding on upper gastrointestinal endoscopy, with an incidence up to 5%. The majority of gastric polyps are asymptomatic, occurring secondary to inflammation. Prior reviews discussed Helicobacter pylori (H pylori)-associated singular gastric polyposis; however, we present a rare and unusual case of recurrent multiple benign gastric polyposis post H pylori eradication resulting in intermittent gastric outlet obstruction. A 70-year-old independent male, Chinese in ethnicity, with a background of diabetes mellitus, hypertension, and a simple renal cyst presented with a combination of melena, anemia, and intermittent vomiting of partially digested food after meals. Initial gastroscopy was positive for H pylori; thus he was treated with H pylori eradication and proton pump inhibitors. Serial gastroscopy demonstrated multiple sessile gastric antral polyps, the largest measuring 4 cm. Histopathologic examination confirmed a benign hyperplastic lesion. Computed tomography identified a pyloric mass with absent surrounding infiltration or metastasis. A distal gastrectomy was performed, whereby multiple small pyloric polyps were found, the largest prolapsing into the pyloric opening, thus explaining the intermittent nature of gastric outlet obstruction. Such polyps often develop from gastric ulcers and, if left untreated, may undergo neoplasia to form malignant cells. A distal gastrectomy was an effective choice of treatment, taking into account the polyp size, quantity, and potential for malignancy as opposed to an endoscopic approach, which may not guarantee a complete removal of safer margins and depth. Therefore, surgical excision is favorable for multiple large gastric polyps with risk of malignancy.

Prolapsing Gastric Polyp Causing Intermittent Gastric Outlet Obstruction

PubMed Central

Kosai, Nik Ritza; Gendeh, Hardip Singh; Norfaezan, Abdul Rashid; Razman, Jamin; Sutton, Paul Anthony; Das, Srijit

2015-01-01

Gastric polyps are often an incidental finding on upper gastrointestinal endoscopy, with an incidence up to 5%. The majority of gastric polyps are asymptomatic, occurring secondary to inflammation. Prior reviews discussed Helicobacter pylori (H pylori)–associated singular gastric polyposis; however, we present a rare and unusual case of recurrent multiple benign gastric polyposis post H pylori eradication resulting in intermittent gastric outlet obstruction. A 70-year-old independent male, Chinese in ethnicity, with a background of diabetes mellitus, hypertension, and a simple renal cyst presented with a combination of melena, anemia, and intermittent vomiting of partially digested food after meals. Initial gastroscopy was positive for H pylori; thus he was treated with H pylori eradication and proton pump inhibitors. Serial gastroscopy demonstrated multiple sessile gastric antral polyps, the largest measuring 4 cm. Histopathologic examination confirmed a benign hyperplastic lesion. Computed tomography identified a pyloric mass with absent surrounding infiltration or metastasis. A distal gastrectomy was performed, whereby multiple small pyloric polyps were found, the largest prolapsing into the pyloric opening, thus explaining the intermittent nature of gastric outlet obstruction. Such polyps often develop from gastric ulcers and, if left untreated, may undergo neoplasia to form malignant cells. A distal gastrectomy was an effective choice of treatment, taking into account the polyp size, quantity, and potential for malignancy as opposed to an endoscopic approach, which may not guarantee a complete removal of safer margins and depth. Therefore, surgical excision is favorable for multiple large gastric polyps with risk of malignancy. PMID:25578789

[A Case of Gastro-Gastric Intussusception Secondary to Primary Gastric Lymphoma].

PubMed

Jo, Hyeong Ho; Kang, Sun Mi; Kim, Si Hye; Ra, Moni; Park, Byeong Kyu; Kwon, Joong Goo; Kim, Eun Young; Jung, Jin Tae; Kim, Ho Gak; Ryoo, Hun Mo; Kang, Ung Rae

2016-07-25

In adults, most intussusceptions develop from a lesion, usually a benign or malignant neoplasm, and can occur at any site in the gastrointestinal tract. Intussusception in the proximal gastrointestinal tract is uncommon, and gastro-gastric intussusception is extremely rare. We present a case of gastro-gastric intussusception secondary to a primary gastric lymphoma. An 82-year-old female patient presented with acute onset chest pain and vomiting. Abdominal CT revealed a gastro-gastric intussusception. We performed upper gastrointestinal endoscopy, revealing a large gastric mass invaginated into the gastric lumen and distorting the distal stomach. Uncomplicated gastric reposition was achieved with endoscopy of the distal stomach. Histological evaluation of the gastric mass revealed a diffuse large B cell lymphoma that was treated with chemotherapy.

Use of lectin microarray to differentiate gastric cancer from gastric ulcer

PubMed Central

Huang, Wei-Li; Li, Yang-Guang; Lv, Yong-Chen; Guan, Xiao-Hui; Ji, Hui-Fan; Chi, Bao-Rong

2014-01-01

AIM: To investigate the feasibility of lectin microarray for differentiating gastric cancer from gastric ulcer. METHODS: Twenty cases of human gastric cancer tissue and 20 cases of human gastric ulcer tissue were collected and processed. Protein was extracted from the frozen tissues and stored. The lectins were dissolved in buffer, and the sugar-binding specificities of lectins and the layout of the lectin microarray were summarized. The median of the effective data points for each lectin was globally normalized to the sum of medians of all effective data points for each lectin in one block. Formalin-fixed paraffin-embedded gastric cancer tissues and their corresponding gastric ulcer tissues were subjected to Ag retrieval. Biotinylated lectin was used as the primary antibody and HRP-streptavidin as the secondary antibody. The glycopatterns of glycoprotein in gastric cancer and gastric ulcer specimens were determined by lectin microarray, and then validated by lectin histochemistry. Data are presented as mean ± SD for the indicated number of independent experiments. RESULTS: The glycosylation level of gastric cancer was significantly higher than that in ulcer. In gastric cancer, most of the lectin binders showed positive signals and the intensity of the signals was stronger, whereas the opposite was the case for ulcers. Significant differences in the pathological score of the two lectins were apparent between ulcer and gastric cancer tissues using the same lectin. For MPL and VVA, all types of gastric cancer detected showed stronger staining and a higher positive rate in comparison with ulcer, especially in the case of signet ring cell carcinoma and intra-mucosal carcinoma. GalNAc bound to MPL showed a significant increase. A statistically significant association between MPL and gastric cancer was observed. As with MPL, there were significant differences in VVA staining between gastric cancer and ulcer. CONCLUSION: Lectin microarray can differentiate the different

Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression.

PubMed

Huang, Feng; Wang, Mei; Yang, Tingting; Cai, Jie; Zhang, Qiang; Sun, Zixuan; Wu, Xiaodan; Zhang, Xu; Zhu, Wei; Qian, Hui; Xu, Wenrong

2014-11-01

This study was designed to investigate the role of PDGF-DD secreted by gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric cancer progression. Gastric cancer cells were indirectly co-cultured with GC-MSCs in a transwell system. The growth and migration of gastric cancer cells were evaluated by cell colony formation assay and transwell migration assay, respectively. The production of PDGF-DD in GC-MSCs was determined by using Luminex and ELISA. Neutralization of PDGFR-β by su16f and siRNA interference of PDGF-DD in GC-MSCs was used to demonstrate the role of PDGF-DD produced by GC-MSCs in gastric cancer progression. GC-MSC conditioned medium promoted gastric cancer cell proliferation and migration in vitro and in vivo. Co-culture with GC-MSCs increased the phosphorylation of PDGFR-β in SGC-7901 cells. Neutralization of PDGFR-β by su16f blocked the promoting role of GC-MSC conditioned medium in gastric cancer cell proliferation and migration. Recombinant PDGF-DD duplicated the effects of GC-MSC conditioned medium on gastric cancer cells. Knockdown of PDGF-DD in GC-MSCs abolished its effects on gastric cancer cells in vitro and in vivo. PDGF-DD secreted by GC-MSCs is capable of promoting gastric cancer cell progression in vitro and in vivo. Targeting the PDGF-DD/PDGFR-β interaction between MSCs and gastric cancer cells may represent a novel strategy for gastric cancer therapy.

Diversity of the Gastric Microbiota in Thoroughbred Racehorses Having Gastric Ulcer.

PubMed

Dong, Hee-Jin; Ho, Hungwui; Hwang, Hyeshin; Kim, Yongbaek; Han, Janet; Lee, Inhyung; Cho, Seongbeom

2016-04-28

Equine gastric ulcer syndrome is one of the most frequently reported diseases in thoroughbred racehorses. Although several risk factors for the development of gastric ulcers have been widely studied, investigation of microbiological factors has been limited. In this study, the presence of Helicobacter spp. and the gastric microbial communities of thoroughbred racehorses having mild to severe gastric ulcers were investigated. Although Helicobacter spp. were not detected using culture and PCR techniques from 52 gastric biopsies and 52 fecal samples, the genomic sequences of H. pylori and H. ganmani were detected using nextgeneration sequencing techniques from 2 out of 10 representative gastric samples. The gastric microbiota of horses was mainly composed of Firmicutes (50.0%), Proteobacteria (18.7%), Bacteroidetes (14.4%), and Actinobacteria (9.7%), but the proportion of each phylum varied among samples. There was no major difference in microbial composition among samples having mild to severe gastric ulcers. Using phylogenetic analysis, three distinct clusters were observed, and one cluster differed from the other two clusters in the frequency of feeding, amount of water consumption, and type of bedding. To the best of our knowledge, this is the first study to investigate the gastric microbiota of thoroughbred racehorses having gastric ulcer and to evaluate the microbial diversity in relation to the severity of gastric ulcer and management factors. This study is important for further exploration of the gastric microbiota in racehorses and is ultimately applicable to improving animal and human health.

Correlation Between Gastric Emptying and Gastric Adaptive Relaxation Influenced by Amino Acids

PubMed Central

Uchida, Masayuki; Kobayashi, Orie; Saito, Chizuru

2017-01-01

Background/Aims Amino acids have many physiological activities. We report the correlation between gastric emptying and gastric adaptive relaxation using tryptophan and amino acids with a straight alkyl chain, hydroxylated chain, and branched chain. Here we sought to further clarify the correlation between gastric emptying and gastric adaptive relaxation by using other amino acids. Methods In Sprague-Dawley rats, gastric emptying was evaluated by a breath test using [1-13C] acetic acid. The expired 13CO2 pattern, Tmax, Cmax, and AUC120min values were used as evaluation items. Gastric adaptive relaxation was evaluated in a barostat experiment. Individual amino acids (1 g/kg) were administered orally 30 minutes before each breath test or barostat test. Results L-phenylalanine and L-tyrosine did not influence gastric emptying. All other amino acids, ie, L-proline, L-histidine, L-cysteine, L-methionine, L-aspartic acid, L-glutamic acid, L-asparagine, L-arginine, L-glutamine, and L-lysine significantly delayed and inhibited gastric emptying. L-Cysteine and L-aspartic acid significantly enhanced and L-methionine and L-glutamine significantly inhibited gastric adaptive relaxation. L-Phenylalanine moved the balloon toward the antrum, suggesting strong contraction of the fundus. Tmax showed a significant positive correlation (r = 0.709), and Cmax and AUC120min each showed negative correlations (r = 0.613 and 0.667, respectively) with gastric adaptive relaxation. Conclusion From the above findings, it was found that a close correlation exists between gastric emptying and adaptive relaxation, suggesting that enhanced gastric adaptive relaxation inhibits gastric emptying. PMID:28335103

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography comparison of gastric lymphoma and gastric carcinoma.

PubMed

Li, Xiao-Feng; Fu, Qiang; Dong, You-Wen; Liu, Jian-Jing; Song, Xiu-Yu; Dai, Dong; Zuo, Cong; Xu, Wen-Gui

2016-09-14

To compare (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma. Patients with newly diagnosed gastric lymphoma or gastric carcinoma who underwent (18)F-FDG PET/CT prior to treatment were included in this study. We reviewed and analyzed the PET/CT features of gastric wall lesions, including FDG avidity, pattern (focal/diffuse), and intensity [maximal standard uptake value: (SUVmax)]. The correlation of SUVmax with gastric clinicopathological variables was investigated by χ(2) test, and receiver-operating characteristic (ROC) curve analysis was performed to determine the differential diagnostic value of SUVmax-associated parameters in gastric lymphoma and gastric carcinoma. Fifty-two patients with gastric lymphoma and 73 with gastric carcinoma were included in this study. Abnormal gastric FDG accumulation was found in 49 patients (94.23%) with gastric lymphoma and 65 patients (89.04%) with gastric carcinoma. Gastric lymphoma patients predominantly presented with type I and type II lesions, whereas gastric carcinoma patients mainly had type III lesions. The SUVmax (13.39 ± 9.24 vs 8.35 ± 5.80, P < 0.001) and SUVmax/THKmax (maximal thickness) (7.96 ± 4.02 vs 4.88 ± 3.32, P < 0.001) were both higher in patients with gastric lymphoma compared with gastric carcinoma. ROC curve analysis suggested a better performance of SUVmax/THKmax in the evaluation of gastric lesions between gastric lymphoma and gastric carcinoma in comparison with that of SUVmax alone. PET/CT features differ between gastric lymphoma and carcinoma, which can improve PET/CT evaluation of gastric wall lesions and help differentiate gastric lymphoma from gastric carcinoma.

18F-fluorodeoxyglucose positron emission tomography/computed tomography comparison of gastric lymphoma and gastric carcinoma

PubMed Central

Li, Xiao-Feng; Fu, Qiang; Dong, You-Wen; Liu, Jian-Jing; Song, Xiu-Yu; Dai, Dong; Zuo, Cong; Xu, Wen-Gui

2016-01-01

AIM To compare 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma. METHODS Patients with newly diagnosed gastric lymphoma or gastric carcinoma who underwent 18F-FDG PET/CT prior to treatment were included in this study. We reviewed and analyzed the PET/CT features of gastric wall lesions, including FDG avidity, pattern (focal/diffuse), and intensity [maximal standard uptake value: (SUVmax)]. The correlation of SUVmax with gastric clinicopathological variables was investigated by χ2 test, and receiver-operating characteristic (ROC) curve analysis was performed to determine the differential diagnostic value of SUVmax-associated parameters in gastric lymphoma and gastric carcinoma. RESULTS Fifty-two patients with gastric lymphoma and 73 with gastric carcinoma were included in this study. Abnormal gastric FDG accumulation was found in 49 patients (94.23%) with gastric lymphoma and 65 patients (89.04%) with gastric carcinoma. Gastric lymphoma patients predominantly presented with type I and type II lesions, whereas gastric carcinoma patients mainly had type III lesions. The SUVmax (13.39 ± 9.24 vs 8.35 ± 5.80, P < 0.001) and SUVmax/THKmax (maximal thickness) (7.96 ± 4.02 vs 4.88 ± 3.32, P < 0.001) were both higher in patients with gastric lymphoma compared with gastric carcinoma. ROC curve analysis suggested a better performance of SUVmax/THKmax in the evaluation of gastric lesions between gastric lymphoma and gastric carcinoma in comparison with that of SUVmax alone. CONCLUSION PET/CT features differ between gastric lymphoma and carcinoma, which can improve PET/CT evaluation of gastric wall lesions and help differentiate gastric lymphoma from gastric carcinoma. PMID:27678362

[AFP-producing gastric cancer and hepatoid gastric cancer].

PubMed

Wang, Y K; Zhang, X T

2017-11-23

AFP-producing gastric cancer(AFPGC) and hepatoid adenocarcinoma of the stomach (HAS) are two special subtypes of gastric cancer. There are both correlation and difference between them. AFPGC is usually identified as primary gastric cancer with serum AFP level more than 20 ng/ml or showed AFP positive staining by immunohistochemistry. The diagnosis of HAS is mainly dependent on the pathological character of hepatocellular carcinoma-like differentiation of gastric cancer. The morbidity of AFPGC and HAS are rather low, especially the incidence of HAS is about 1%. The prognoses of these two subtypes are poorer than that of common gastric adenocarcinoma, due to a high incidence rate of liver metastasis and lymph node metastasis. With the development of next-generation sequencing and other genomic technologies, gastric cancers, including these two rare subtypes, are now being investigated in more detail at the molecular level. Treatment remains the biggest challenge, early diagnosis and radical resection can dramatically improve patients'prognosis. Monitoring serum AFP and abdominal imaging examination during follow-up is important for early detection of liver metastasis. In combination with local treatment methods such as transarterial chemoembolization and radiofrequency ablation of liver may further extend patients'survival time. Targeted therapy owes a great potential value in the future.

Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma.

PubMed

Inaba, Koji; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun

2013-10-26

There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

Hereditary Diffuse Gastric Cancer

MedlinePlus

... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

Role of gastric mucosal and gastric juice cytokine concentrations in development of bisphosphonate damage to gastric mucosa.

PubMed

Thomson, A B R; Appleman, S; Keelan, M; Wallace, J L

2003-02-01

Previous studies have shown that the bisphosphonates (BP) vary in their damaging effect on the gastric mucosa, and endoscopy scores (erosions or erosions plus ulcers) after 1 and 2 weeks use of BP were significantly lower in H. pylori-positive versus -negative subjects. The mechanism of this damaging effect of BP and the interaction with H. pylori is unknown. As part of a separately reported study of the incidence of gastric damage after 2 weeks of treatment of healthy female postmenopausal volunteers with risedronate (5 mg/day) or alendronate (10 mg/day), gastric aspirates were taken at the time of the baseline esophagogastroduodenoscopy (EGD), and again at 1 and 2 weeks after daily intake of a BP At the time of the third EGD, when the volunteers had been on risedronate or alendronate for 2 weeks, antral biopsies were taken from normal-appearing mucosa. Gastric juice and antral biopsies were assessed for their concentration of the cytokines interleukin-la (IL-1alpha), IL-8, IL-13, and epidermal growth factor (EGF). H. pylori, the use of BP, and development of gastric mucosal lesions had no effect on gastric mucosal concentrations of IL-1alpha, IL-13, or EGF. In contrast, the concentration of IL-8 in antral mucosal biopsies of volunteers given BP for 2 weeks was higher in the presence than in the absence of an H. pylori infection and was increased further in those who develop lesions associated with the use of BP. There was no correlation between gastric mucosal and gastric juice concentrations of IL-8. Gastric juice concentrations of IL-8 and EGF were not affected by H. pylori status, the use of BP, or the development of lesions. However, gastric juice concentrations of IL-1alpha were numerically lower in those who were negative for H. pylori with no mucosal lesions (Hp-L-), intermediate in those who were H. pylori-negative with lesions (Hp-L+), and highest in those who were positive for H. pylori and had lesions (Hp+L+). The gastric juice concentration of IL-13

Gastric neuromuscular histology in patients with refractory gastroparesis: Relationships to etiology, gastric emptying, and response to gastric electric stimulation.

PubMed

Heckert, J; Thomas, R M; Parkman, H P

2017-08-01

The aims of this study were to describe the histology in gastroparesis, specifically to relate histopathology to etiology of gastroparesis (idiopathic and diabetic gastroparesis), gastric emptying, and clinical response to gastric electric stimulation. Full thickness gastric body sections obtained during insertion of gastric stimulator in gastroparetics were stained with Hematoxylin & Eosin, Masson Trichrome and immunohistochemical stains for Neuron-Specific Enolase and c-Kit. In all, 145 gastroparetics (71 diabetics, 71 idiopathic, 2 post-surgical, and 1 chronic intestinal pseudo-obstruction) had full thickness gastric body biopsies. A lymphocytic infiltrate was seen in the intermyenteric plexus in 22 diabetic and 23 idiopathic gastroparesis patients. Fibrosis was present in the inner circular layer in 13 diabetic and 15 idiopathics and in the outer longitudinal layer in 46 diabetic and 51 idiopathics. Diabetic gastroparesis had less ganglion cells (3.27±1.82 vs 4.81±2.81/hpf; P<.01) and less ganglia (0.90±0.44 vs 1.10±0.50/hpf; P=.01) than idiopathic gastroparesis. Interstitial cells of Cajal (ICC) count was slightly lower in the inner circular layer in diabetic than idiopathics (2.77±1.47 vs 3.18±1.34/hpf; P=.08). Delayed gastric emptying was associated with reduced ICCs in the myenteric plexus. Global therapeutic response to gastric electric stimulation was inversely related to ganglia/hpf (R=-.22; P=.008). In diabetics, improvements in nausea, vomiting, and abdominal pain were inversely related to fibrosis. Histologic assessment of full thickness gastric biopsy specimens allows correlation of histopathology to the gastroparesis disease process, its etiology, gastric emptying, and response to gastric electric stimulation treatment. © 2017 John Wiley & Sons Ltd.

Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia

PubMed Central

Asano, Teita; Aida, Shuji; Suemasu, Shintaro; Tahara, Kayoko; Tanaka, Ken-ichiro; Mizushima, Tohru

2015-01-01

Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here. PMID:26620883

Autoimmunity and Gastric Cancer

PubMed Central

Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

2018-01-01

Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer

PubMed Central

Ding, Lin; El Zaatari, Mohamad

2017-01-01

Overview Gastric cancer has been traditionally defined by the Correa paradigm as a progression of sequential pathological events that begins with chronic inflammation [1]. Infection with Helicobacter pylori (H. pylori) is the typical explanation for why the stomach becomes chronically inflamed. Acute gastric inflammation then leads to chronic gastritis, atrophy particularly of acid-secreting parietal cells, metaplasia due to mucous neck cell expansion from trans-differentiation of zymogenic cells to dysplasia and eventually carcinoma [2]. The chapter contains an overview of gastric anatomy and physiology to set the stage for signaling pathways that play a role in gastric tumorigenesis. Finally, the major known mouse models of gastric transformation are critiqued in terms of the rationale behind their generation and contribution to our understanding of human cancer subtypes. PMID:27573785

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings of gastric lymphoma: Comparisons with gastric cancer.

PubMed

Wu, Jiang; Zhu, Hong; Li, Kai; Wang, Xin-Gang; Gui, Yi; Lu, Guang-Ming

2014-10-01

The role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in numerous malignant tumors, including gastric lymphoma, is well-established. However, there have been few studies with regard to the 18 F-FDG PET/CT features of gastric lymphoma. The aim of the present study was to characterize the 18 F-FDG PET/CT features of gastric lymphoma, which were compared with those of gastric cancer. Prior to treatment, 18 F-FDG PET/CT was performed on 24 patients with gastric lymphoma and 43 patients with gastric cancer. The 18 F-FDG PET/CT pattern of gastric wall lesions was classified as one of three types: Type I, diffuse thickening of the gastric wall with increased FDG uptake infiltrating more than one-third of the total stomach; type II, segmental thickening of the gastric wall with elevated FDG uptake involving less than one-third of the total stomach; and type III, local thickening of the gastric wall with focal FDG uptake. The incidence of the involvement of more than one region of the stomach was higher in the patients with gastric lymphoma than in those with gastric cancer. Gastric FDG uptake was demonstrated in 23 of the 24 patients (95.8%) with gastric lymphoma and in 40 of the 43 patients (93.0%) with gastric cancer. Gastric lymphoma predominantly presented with type I and II lesions, whereas gastric cancer mainly presented with type II and III lesions. The maximal thickness was larger and the maximal standard uptake value (SUV max ) was higher in the patients with gastric lymphoma compared with those with gastric cancer. A positive correlation between the maximal thickness and SUV max was confirmed for the gastric cancer lesions, but not for the gastric lymphoma lesions. There was no difference in the maximal thickness and SUV max of the gastric wall lesions between the patients without and with extragastric involvement, for gastric lymphoma and gastric cancer. Overall, certain differences exist in the findings between

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings of gastric lymphoma: Comparisons with gastric cancer

PubMed Central

WU, JIANG; ZHU, HONG; LI, KAI; WANG, XIN-GANG; GUI, YI; LU, GUANG-MING

2014-01-01

The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in numerous malignant tumors, including gastric lymphoma, is well-established. However, there have been few studies with regard to the 18F-FDG PET/CT features of gastric lymphoma. The aim of the present study was to characterize the 18F-FDG PET/CT features of gastric lymphoma, which were compared with those of gastric cancer. Prior to treatment, 18F-FDG PET/CT was performed on 24 patients with gastric lymphoma and 43 patients with gastric cancer. The 18F-FDG PET/CT pattern of gastric wall lesions was classified as one of three types: Type I, diffuse thickening of the gastric wall with increased FDG uptake infiltrating more than one-third of the total stomach; type II, segmental thickening of the gastric wall with elevated FDG uptake involving less than one-third of the total stomach; and type III, local thickening of the gastric wall with focal FDG uptake. The incidence of the involvement of more than one region of the stomach was higher in the patients with gastric lymphoma than in those with gastric cancer. Gastric FDG uptake was demonstrated in 23 of the 24 patients (95.8%) with gastric lymphoma and in 40 of the 43 patients (93.0%) with gastric cancer. Gastric lymphoma predominantly presented with type I and II lesions, whereas gastric cancer mainly presented with type II and III lesions. The maximal thickness was larger and the maximal standard uptake value (SUVmax) was higher in the patients with gastric lymphoma compared with those with gastric cancer. A positive correlation between the maximal thickness and SUVmax was confirmed for the gastric cancer lesions, but not for the gastric lymphoma lesions. There was no difference in the maximal thickness and SUVmax of the gastric wall lesions between the patients without and with extragastric involvement, for gastric lymphoma and gastric cancer. Overall, certain differences exist in the findings between gastric

Successful Emergency Endoscopic Treatment of Gastric Outlet Obstruction due to Gastric Bezoar with Gastric Pneumatosis

PubMed Central

Honda, Hirokazu; Ikeya, Takashi; Kashiwagi, Erika; Okada, Shuichi; Fukuda, Katsuyuki

2017-01-01

Gastric bezoars are rare and are usually found incidentally. They can sometimes cause severe complications, including gastric outlet obstruction (GOO) or gastric pneumatosis (GP). In cases of bezoars with GP, the optimal treatment strategy has not yet been defined. We report the case of an 89-year-old man with a history of type 2 diabetes mellitus and hypertension who presented to our emergency room with a 2-day history of upper abdominal pain, nausea, and vomiting. Physical examination revealed no rebound tenderness or guarding, and laboratory values revealed no elevation of the serum lactate level. A computed tomography scan of the abdomen showed a dilated stomach with significant fluid collection, GOO, and GP due to a 42 × 40 mm mass composed of fat and air densities. Emergency esophagogastroduodenoscopy revealed two gastric bezoars, one of which was incarcerated in the pyloric region. We used various endoscopic devices to successfully break and remove the bezoars. We used endoscopic forceps and a water jet followed by an endoscopic snare to cut the bezoars into several pieces and remove them with an endoscopic net. Follow-up endoscopy confirmed that the gastric bezoar had been completely removed. As seen in this case, endoscopic treatment may be a safe and viable option for the extraction of gastric bezoars presenting with GOO and GP. PMID:29430223

Successful Emergency Endoscopic Treatment of Gastric Outlet Obstruction due to Gastric Bezoar with Gastric Pneumatosis.

PubMed

Honda, Hirokazu; Ikeya, Takashi; Kashiwagi, Erika; Okada, Shuichi; Fukuda, Katsuyuki

2017-01-01

Gastric bezoars are rare and are usually found incidentally. They can sometimes cause severe complications, including gastric outlet obstruction (GOO) or gastric pneumatosis (GP). In cases of bezoars with GP, the optimal treatment strategy has not yet been defined. We report the case of an 89-year-old man with a history of type 2 diabetes mellitus and hypertension who presented to our emergency room with a 2-day history of upper abdominal pain, nausea, and vomiting. Physical examination revealed no rebound tenderness or guarding, and laboratory values revealed no elevation of the serum lactate level. A computed tomography scan of the abdomen showed a dilated stomach with significant fluid collection, GOO, and GP due to a 42 × 40 mm mass composed of fat and air densities. Emergency esophagogastroduodenoscopy revealed two gastric bezoars, one of which was incarcerated in the pyloric region. We used various endoscopic devices to successfully break and remove the bezoars. We used endoscopic forceps and a water jet followed by an endoscopic snare to cut the bezoars into several pieces and remove them with an endoscopic net. Follow-up endoscopy confirmed that the gastric bezoar had been completely removed. As seen in this case, endoscopic treatment may be a safe and viable option for the extraction of gastric bezoars presenting with GOO and GP.

Cisplatin-induced gastric dysrhythmia and emesis in dogs and possible role of gastric electrical stimulation.

PubMed

Yu, Xiaoyun; Yang, Jie; Hou, Xiaohua; Zhang, Kan; Qian, Wei; Chen, J D Z

2009-05-01

The aim of this study was to investigate the effect of cisplatin on gastric myoelectrical activity and the role of gastric electrical stimulation in the treatment of cisplatin-induced emesis in dogs. Seven dogs implanted with electrodes on the gastric serosa were used in a two-session study. Cisplatin was infused in both the control session and the gastric electrical stimulation session, and gastric electrical stimulation was applied in the gastric electrical stimulation session. Gastric slow waves and emesis, as well as behaviors suggestive of nausea, were recorded during each session. The results were as follows: (1) cisplatin induced vomiting and other symptoms and induced gastric dysrhythmia. The percentage of normal slow waves decreased significantly during the 2.5 h before vomiting (P=0.01) and the period of vomiting (P<0.001). (2) Gastric electrical stimulation reduced emesis and the symptoms score. The total score in the control session was higher than that in the gastric electrical stimulation session (P=0.02). However, gastric electrical stimulation had no effects on gastric dysrhythmia. It is concluded that cisplatin induces emesis and gastric dysrhythmia. Gastric electrical stimulation may play a role in relieving chemotherapy-induced emetic responses and deserves further investigation.

Experimental studies of gastric dysfunction in motion sickness: The effect of gastric and vestibular stimulation on the vagal and splanchnic gastric efferents

NASA Technical Reports Server (NTRS)

Niijima, A.; Jiang, Z. Y.; Daunton, Nancy G.; Fox, Robert A.

1991-01-01

The experiments were conducted in anaesthetized rats. In the first part of the experiments, the effect of CuSO4 on the afferent activity in the gastric branch of the vagus nerve was investigated. Gastric perfusion of CuSO4 solution (0.04 percent and 0.08 percent) provoked an increase in afferent activity. In the second part of the experiments, the reflex effects of gastric perfusion of CuSO4 solution, repetitive stimulation of the gastric vagus nerve, and caloric stimulation of the right vestibular apparatus (5-18 C water) on gastric autonomic outflow were investigated. The results of these experiments showed that these three different types of stimulation caused an inhibition in efferent activity of the gastric vagus nerve and a slight activation of the splanchnic gastric efferents. The summation of the effect of each stimulation was also observed. These results, therefore, provide evidence for a possible integrative inhibitory function of the vagal gastric center as well as an excitatory function of gastric sympathetic motoneurons in relation to motion sickness.

Radiological findings of gastric adenomyoma in a neonate presenting with gastric outlet obstruction.

PubMed

Rhim, Jung Hyo; Kim, Woo Sun; Choi, Young Hun; Cheon, Jung-Eun; Park, Sung Hye

2013-03-01

Gastric adenomyoma is a rare tumour-like lesion composed of glandular components and smooth muscle bundles. We report a case of gastric adenomyoma in a 1-week-old neonate who presented with gastric outlet obstruction. To the best of our knowledge, this is the youngest child reported with gastric adenomyoma and a unique case demonstrating radiological findings of gastric adenomyoma in a young infant. At US, the lesion was seen as an asymmetrical mass-like wall-thickening of the pylorus. Upper gastrointestinal series showed findings similar to those seen in a case of hypertrophic pyloric stenosis. We suggest that gastric adenomyoma should be included in the causes of gastric outlet obstruction in neonates even though it is rare in young children.

Endoscopic Evaluation of Gastric Emptying and Effect of Mosapride Citrate on Gastric Emptying

PubMed Central

Jung, In Su; Kim, Jie-Hyun; Lee, Hwal Youn; Lee, Sang In

2010-01-01

Purpose Gastric emptying has been evaluated by scintigraphy in spite of its limitations of time consumption, cost, and danger of radioisotope. Endoscopy is a simple technique, however, its validation for gastric emptying and quantification of food has not yet been investigated. The aim of our study was to assess endoscopic gastric emptying compared with scintigraphy and radiopaque markers (ROMs) studies. We also investigated the effect of a single dose of mosapride on gastric emptying. Materials and Methods Fifteen healthy volunteers underwent scintigraphy. Next day, subjects received a standard solid meal with ROMs and underwent endoscopy and simple abdomen X-ray after 3 hrs. After one week, the same procedure was repeated after ingestion of mosapride (5 mg for group 1, n = 8; 10 mg for group 2, n = 7) 15 min before the meal. Quantification of gastric residue by endoscopy was scored from 0 to 3, and the scores were added up. Results All subjects completed the study without any complication. The gastric emptying rate [T1/2 (min)] was in normal range (65.6 ± 12.6 min). Endoscopic gastric emptying was correlated significantly with gastric clearance of ROMs (r = 0.627, p = 0.012). Endoscopic gastric emptying and gastric clearance of ROMs after administration of mosapride showed significant differences in the 10 mg group (p < 0.05). Conclusion Endoscopy can evaluate gastric emptying safely and simply on an outpatient basis. A 10 mg dose of mosapride enhanced gastric emptying, assessed by both endoscopy and ROMs. PMID:20046511

Distension-Induced Gastric Contraction is Attenuated in an Experimental Model of Gastric Restraint

PubMed Central

Lu, Xiao; Guo, Xiaomei; Mattar, Samer G.; Navia, Jose A.

2010-01-01

Background Gastric distension has important implications for motility and satiety. The hypothesis of this study was that distension affects the amplitude and duration of gastric contraction and that these parameters are largely mediated by efferent vagus stimulation. Methods A novel isovolumic myograph was introduced to test these hypotheses. The isovolumic myograph isolates the stomach and records the pressure generated by the gastric contraction under isovolumic conditions. Accordingly, the phasic changes of gastric contractility can be documented. A group of 12 rats were used under in vivo conditions and isolated ex vivo conditions and with two different gastric restraints (small and large) to determine the effect of degree of restraint. Results The comparison of the in vivo and ex vivo contractility provided information on the efferent vagus mediation of gastric contraction, i.e., the in vivo amplitude and duration reached maximum of 12.6 ± 2.7 mmHg and 19.8 ± 5.6 s in contrast to maximum of 5.7 ± 0.9 mmHg and 7.3 ± 1.3 s in ex vivo amplitude and duration, respectively. The comparison of gastric restraint and control groups highlights the role of distension on in vivo gastric contractility. The limitation of gastric distension by restraint drastically reduced the maximal amplitude to below 2.9 ± 0.2 mmHg. Conclusions The results show that distension-induced gastric contractility is regulated by both central nervous system and local mechanisms with the former being more substantial. Furthermore, the gastric restraint significantly attenuates gastric contractility (decreased amplitude and shortened duration of contraction) which is mediated by the efferent vagus activation. These findings have important implications for gastric motility and physiology and may improve our understanding of satiety. PMID:20706803

Gastric intestinal metaplasia is associated with gastric dysplasia but is inversely correlated with esophageal dysplasia

PubMed Central

Gomez, Justin M; Patrie, James T; Bleibel, Wissam; Frye, Jeanetta W; Sauer, Bryan G; Shami, Vanessa M; Stelow, Edward B; Moskaluk, Christopher A; Wang, Andrew Y

2017-01-01

AIM To determine which clinical factors might be associated with gastric intestinal metaplasia (IM) in a North American population. METHODS Pathology and endoscopy databases at an academic medical center were reviewed to identify patients with and without gastric IM on biopsies for a retrospective cohort study. Patient demographics, insurance status, and other clinical factors were reviewed. RESULTS Four hundred and sixty-eight patients with gastric IM (mean age: 61.0 years ± 14.4 years, 55.5% female) and 171 without gastric IM (mean age: 48.8 years ± 20.8 years, 55.0% female) were compared. The endoscopic appearance of atrophic gastritis correlated with finding gastric IM on histopathology (OR = 2.05, P = 0.051). Gastric IM was associated with histologic findings of chronic gastritis (OR = 2.56, P < 0.001), gastric ulcer (OR = 6.97, P = 0.015), gastric dysplasia (OR = 6.11, P = 0.038), and gastric cancer (OR = 6.53, P = 0.027). Histologic findings of Barrett’s esophagus (OR = 0.28, P = 0.003) and esophageal dysplasia (OR = 0.11, P = 0.014) were inversely associated with gastric IM. Tobacco use (OR = 1.73, P = 0.005) was associated with gastric IM. CONCLUSION Patients who smoke or have the endoscopic finding of atrophic gastritis are more likely to have gastric IM and should have screening gastric biopsies during esophagogastroduodenoscopy (EGD). Patients with gastric IM are at increased risk for having gastric dysplasia and cancer, and surveillance EGD with gastric biopsies in these patients might be reasonable. PMID:28250898

Sensitive and specific detection of early gastric cancer with DNA methylation analysis of gastric washes.

PubMed

Watanabe, Yoshiyuki; Kim, Hyun Soo; Castoro, Ryan J; Chung, Woonbok; Estecio, Marcos R H; Kondo, Kimie; Guo, Yi; Ahmed, Saira S; Toyota, Minoru; Itoh, Fumio; Suk, Ki Tae; Cho, Mee-Yon; Shen, Lanlan; Jelinek, Jaroslav; Issa, Jean-Pierre J

2009-06-01

Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 nonneoplastic gastric mucosa samples. Six genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test, and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer, whereas PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r = 0.5-0.9, P = .03-.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the receiver operating characteristic curve (0.961) in terms of tumor detection in gastric washes. These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally, we have developed a new method for gastric cancer detection by DNA methylation in gastric washes.

Gastric cancer stem cells in gastric carcinogenesis, progression, prevention and treatment

PubMed Central

Li, Kang; Dan, Zeng; Nie, Yu-Qiang

2014-01-01

In recent decades, the study of the mechanism of tumorigenesis has brought much progress to cancer treatment. However, cancer stem cell (CSC) theory has changed previous views of tumors, and has provided a new method for treatment of cancer. The discovery of CSCs and their characteristics have contributed to understanding the molecular mechanism of tumor genesis and development, resulting in a new effective strategy for cancer treatment. Gastric CSCs (GCSCs) are the basis for the onset of gastric cancer. They may be derived from gastric stem cells in gastric tissues, or bone marrow mesenchymal stem cells. As with other stem cells, GCSCs highly express drug-resistance genes such as aldehyde dehydrogenase and multidrug resistance, which are resistant to chemotherapy and thus form the basis of drug resistance. Many specific molecular markers such as CD44 and CD133 have been used for identification and isolation of GCSCs, diagnosis and grading of gastric cancer, and research on GCSC-targeted therapy for gastric cancer. Therefore, discussion of the recent development and advancements in GCSCs will be helpful for providing novel insight into gastric cancer treatment. PMID:24833872

Essential role of gastric gland mucin in preventing gastric cancer in mice

PubMed Central

Karasawa, Fumitoshi; Shiota, Akira; Goso, Yukinobu; Kobayashi, Motohiro; Sato, Yoshiko; Masumoto, Junya; Fujiwara, Maiko; Yokosawa, Shuichi; Muraki, Takashi; Miyagawa, Shinichi; Ueda, Masatsugu; Fukuda, Michiko N.; Fukuda, Minoru; Ishihara, Kazuhiko; Nakayama, Jun

2012-01-01

Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Previously, we identified human α1,4-N-acetylglucosaminyltransferase (α4GnT), which is responsible for the O-glycan biosynthesis and characterized αGlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt–/– mice to better understand its role in vivo. A4gnt–/– mice showed complete lack of αGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt–/– mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced αGlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of αGlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, αGlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation. PMID:22307328

Clinicopathological characteristics and therapeutic outcomes of synchronous gastric adenocarcinoma and gastric lymphoma.

PubMed

Namikawa, Tsutomu; Munekage, Eri; Fukudome, Ian; Maeda, Hiromichi; Kitagawa, Hiroyuki; Togitani, Kazuto; Takasaki, Motohiro; Yokoyama, Akihito; Kobayashi, Michiya; Hanazaki, Kazuhiro

2014-09-01

Synchronous primary gastric adenocarcinoma and lymphoma is a rare occurrence. The aim of the present retrospective study was to analyze the clinicopathological characteristics and therapeutic outcomes of patients with this rare condition to identify post-therapeutic prognostic factors. A PubMed and MEDLINE search was performed to identify relevant articles, using the keywords 'gastric cancer' and 'gastric malignant lymphoma', while additional articles were obtained from references within these papers. A total of 57 patients who were treated for synchronous primary gastric adenocarcinoma and lymphoma were included in the study. A retrospective review was performed on the clinical characteristics of this disease. The median survival time for patients in this study was 81 months and the overall 1- and 5-year survival rates after therapy were 77.6% and 69.0%, respectively. The median survival period of patients with an advanced gastric cancer was significantly shorter than for early gastric cancer (p<0.001), while the depth of gastric lymphoma invasion did not significantly affect survival time. The median survival period of patients who underwent total gastrectomy was significantly shorter than that of those who underwent distal gastrectomy (p=0.035). Gastric lymphomas were significantly larger than the gastric adenocarcinomas (6.0 vs. 2.7 cm, respectively; p=0.012). The prognosis for synchronous gastric adenocarcinoma and lymphoma might depend more on the behavior of the adenocarcinoma than on the lymphoma, in which case the treatment and therapeutic outcomes could depend on the adenocarcinoma status. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Itopride for gastric volume, gastric emptying and drinking capacity in functional dyspepsia.

PubMed

Abid, Shahab; Jafri, Wasim; Zaman, Maseeh Uz; Bilal, Rakhshanda; Awan, Safia; Abbas, Aamir

2017-02-06

To study the effect of itopride on gastric accommodation, gastric emptying and drinking capacity in functional dyspepsia (FD). Randomized controlled trial was conducted to check the effect of itopride on gastric accommodation, gastric emptying, capacity of tolerating nutrient liquid and symptoms of FD. We recruited a total of 31 patients having FD on the basis of ROME III criteria. After randomization, itopride was received by 15 patients while 16 patients received placebo. Gastric accommodation was determined using Gastric Scintigraphy. 13 C labeled octanoic breadth test was performed to assess gastric emptying. Capacity of tolerating nutrient liquid drink was checked using satiety drinking capacity test. The intervention group comprised of 150 mg itopride. Patients in both arms were followed for 4 wk. Mean age of the recruited participant 33 years (SD = 7.6) and most of the recruited individuals, i.e ., 21 (67.7%) were males. We found that there was no effect of itopride on gastric accommodation as measured at different in volumes in the itopride and control group with the empty stomach ( P = 0.14), at 20 min ( P = 0.38), 30 min ( P = 0.30), 40 min ( P = 0.43), 50 min ( P = 0.50), 60 min ( P = 0.81), 90 min ( P = 0.25) and 120 min ( P = 0.67). Gastric emptying done on a sub sample ( n = 11) showed no significant difference ( P = 0.58) between itopride and placebo group. There was no significant improvement in the capacity to tolerate liquid in the itopride group as compared to placebo ( P = 0.51). Similarly there was no significant improvement of symptoms as assessed through a composite symptom score ( P = 0.74). The change in QT interval in itopride group was not significantly different from placebo (0.10). Our study found no effect of itopride on gastric accommodation, gastric emptying and maximum tolerated volume in patients with FD.

Gastric tumours in FAP.

PubMed

Walton, Sarah-Jane; Frayling, Ian M; Clark, Susan K; Latchford, Andrew

2017-07-01

Gastric cancer is not a recognised extra-colonic manifestation of FAP, except in countries with a high prevalence of gastric cancer. Data regarding gastric adenomas in FAP are sparse. The aim of this study was to review the clinical characteristics of gastric tumours occurring within an FAP population from the largest European polyposis registry. All patients that developed a gastric adenoma or carcinoma were identified from a prospectively maintained registry database. The primary outcome measure was the occurrence of gastric adenoma or adenocarcinoma. Secondary outcomes included APC mutation, tumour stage, management and survival. Eight patients developed gastric cancer and 21 an adenoma (median age 52 and 44 years, respectively). Regular oesophagogastroduodenoscopy surveillance was performed in 6/8 patients who developed cancer. Half were advanced T3/4 tumours and 6/8 had nodal or metastatic spread at diagnosis. All cancer cases died within a median of 13.5 months from diagnosis. Gastric adenomas were evenly distributed: 11/21 (52%) in the distal and 10/21 (48%) proximal stomach, whereas 5/8 (63%) cancers were located proximally. An association between gastric tumour and desmoid development was observed; 7/8 (88%) cancer and 11/21 (52%) adenoma cases had a personal or family history of desmoid. It would appear from this small, retrospective study that gastric cancer is not a prominent extra-colonic feature of FAP in the Western world. It seems to present at an advanced stage with a poor prognosis. There may be an association between gastric tumour and desmoid occurrence but a large multicentre cohort is necessary to investigate this further.

Endoscopic gastric atrophy is strongly associated with gastric cancer development after Helicobacter pylori eradication.

PubMed

Toyoshima, Osamu; Yamaji, Yutaka; Yoshida, Shuntaro; Matsumoto, Shuhei; Yamashita, Hiroharu; Kanazawa, Takamitsu; Hata, Keisuke

2017-05-01

Risk factors for gastric cancer during continuous infection with Helicobacter pylori have been well documented; however, little has been reported on the risk factors for primary gastric cancer after H. pylori eradication. We conducted a retrospective, endoscopy-based, long-term, large-cohort study to clarify the risk factors for gastric cancer following H. pylori eradication. Patients who achieved successful H. pylori eradication and periodically underwent esophagogastroduodenoscopy surveillance thereafter at Toyoshima Endoscopy Clinic were enrolled. The primary endpoint was the development of gastric cancer. Statistical analysis was performed using the Kaplan-Meier method and Cox's proportional hazards models. Gastric cancer developed in 15 of 1232 patients. The cumulative incidence rates were 1.0 % at 2 years, 2.6 % at 5 years, and 6.8 % at 10 years. Histology showed that all gastric cancers (17 lesions) in the 15 patients were of the intestinal type, within the mucosal layer, and <20 mm in diameter. Based on univariate analysis, older age and higher endoscopic grade of gastric atrophy were significantly associated with gastric cancer development after eradication of H. pylori, and gastric ulcers were marginally associated. Multivariate analysis identified higher grade of gastric atrophy (hazard ratio 1.77; 95 % confidence interval 1.12-2.78; P = 0.01) as the only independently associated parameter. Endoscopic gastric atrophy is a major risk factor for gastric cancer development after H. pylori eradication. Further long-term studies are required to determine whether H. pylori eradication leads to regression of H. pylori-related gastritis and reduces the risk of gastric cancer.

Effect of acute gastric dilatation on gastric myoelectic and motor activity in dogs.

PubMed

Hall, J A; Solie, T N; Seim, H B; Twedt, D C

1999-05-01

To investigate the effects of experimentally induced acute gastric dilatation on electrical and mechanical activities of the stomach in dogs. 7 healthy dogs. Electrodes and strain-gauge force transducers were implanted on the serosal surface of the antrum and pylorus. Eight days later, baseline gastric electrical and contractile activities were recorded. The dogs were anesthetized and mechanically ventilated to maintain normocapnia while the stomach was distended (intragastric pressure, 30 mm Hg) for 180 minutes, using a thin compliant bag. Gastric electrical and contractile activities were recorded again on days 1 and 10 after dilatation. Recordings were analyzed to determine gastric slow-wave frequency, slow-wave dysrhythmia, propagation velocity of slow-waves, coupling of contractions to slow waves, motility index on the basis of relative contractile amplitudes, and onset of contractions after a standardized meal. Electrical or contractile activities were not significantly different 18 hours after acute gastric dilatation (day 1). Arrhythmias were evident before and after gastric dilatation in dogs from which food was withheld and in dogs after consumption of a meal. Variables for assessing gastric electrical and contractile activities were unaffected 18 hours after acute gastric dilatation. Analysis of results of this study indicated that altered electrical and contractile activities in dogs with short-term gastric dilatation are not likely to be secondary to the process of acute gastric dilatation.

Sensitive and Specific Detection of Early Gastric Cancer Using DNA Methylation Analysis of Gastric Washes

PubMed Central

Watanabe, Yoshiyuki; Kim, Hyun Soo; Castoro, Ryan J.; Chung, Woonbok; Estecio, Marcos R. H.; Kondo, Kimie; Guo, Yi; Ahmed, Saira S.; Toyota, Minoru; Itoh, Fumio; Suk, Ki Tae; Cho, Mee-Yon; Shen, Lanlan; Jelinek, Jaroslav; Issa, Jean-Pierre J.

2009-01-01

Background & Aims Aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. We hypothesized that methylation analysis of DNA recovered from gastric washes could be used to detect gastric cancer. Methods We studied 51 candidate genes in 7 gastric cancer cell lines and 24 samples (training set) and identified 6 for further studies. We examined the methylation status of these genes in a test set consisting of 131 gastric neoplasias at various stages. Finally, we validated the 6 candidate genes in a different population of 40 primary gastric cancer samples and 113 non-neoplastic gastric mucosa samples. Results 6 genes (MINT25, RORA, GDNF, ADAM23, PRDM5, MLF1) showed frequent differential methylation between gastric cancer and normal mucosa in the training, test and validation sets. GDNF and MINT25 were most sensitive molecular markers of early stage gastric cancer while PRDM5 and MLF1 were markers of a field defect. There was a close correlation (r=0.5 to 0.9, p=0.03 to 0.001) between methylation levels in tumor biopsy and gastric washes. MINT25 methylation had the best sensitivity (90%), specificity (96%), and area under the ROC curve (0.961) in terms of tumor detection in gastric washes. Conclusions These findings suggest MINT25 is a sensitive and specific marker for screening in gastric cancer. Additionally we have developed a new methodology for gastric cancer detection by DNA methylation in gastric washes. PMID:19375421

Downregulation of STARD8 in gastric cancer and its involvement in gastric cancer progression

PubMed Central

Ma, Jinguo; Chen, Jing; Zhi, Yu; Li, Zhenhua; Dai, Dongqiu

2018-01-01

Objective Rho-GTPases play a pivotal role in a wide variety of signal transduction pathways and are associated with a great number of human carcinomas. STARD8, which is a Rho-GTPase-activating protein, has been proposed as a tumor suppressor gene, but its role in gastric cancer remains elusive. In this study, we investigate the expression of STARD8 in gastric cancer and its association with gastric cancer progression. Materials and methods One normal gastric mucosa cell line for example GES1 and six human gastric cancer cell lines such as AGS, MGC803, MKN45, SGC7901, HGC27 and BGC823 were utilized to analyze STARD8 mRNA and protein levels by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. A total of 70 paired gastric tissues including corresponding nonmalignant gastric tissues and cancer tissues were utilized to analyze the protein expression of STARD8 using immunohistochemistry, and the correlation between STARD8 level and clinicopathological features was also evaluated. Results STARD8 was found to be downregulated in primary gastric cancer cells and tissues compared with the normal gastric mucosa cell line, GES1, and corresponding nonmalignant gastric tissues, while its decreased expression was significantly associated with TNM stage, lymph node metastasis and differentiation (p<0.05). Conclusion There is significantly decreased expression of STARD8 in gastric cancer cells and tissues, and its expression may contribute to gastric tumorigenesis. PMID:29849465

Mesentero-axial gastric volvulus after removal of laparoscopic adjustable gastric band.

PubMed

Pirmadjid, N; Pournaras, D J; Huan, S; Sujendran, V

2017-02-01

Despite the decreasing popularity of gastric banding, a large number of patients still have a band in situ. Although immediate postoperative complications are relatively rare, long-term complications of gastric banding are more common but are not reported to occur after band removal. We report a case of gastric volvulus and subsequent ischaemic perforation in a patient shortly after band removal, resulting in emergency laparotomy and total gastrectomy. Severe continuing pain persisting after band deflation and even gastric band removal should be treated as an emergency and urgent investigation should not be delayed.

History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer

PubMed Central

Graham, David Y

2014-01-01

Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for “surgical disease” or for “Sippy” diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori

History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer.

PubMed

Graham, David Y

2014-05-14

Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician's believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for "surgical disease" or for "Sippy" diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori-related diseases.

A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissues.

PubMed

Aziz, Faisal; Yang, Xuesong; Wen, Qingping; Yan, Qiu

2015-08-01

At present, biopsy specimens, cancer cell lines and tissues obtained by gastric surgery are used in the study and analysis of gastric cancer, including the molecular mechanisms and proteomics. However, fibroblasts and other tissue components may interfere with these techniques. Therefore, the present study aimed to develop a procedure for the isolation of viable human gastric epithelial cells from gastric surgical tissues. A method was developed to culture human gastric epithelial cells using fresh, surgically excised tissues and was evaluated using immunocytochemistry, periodic acid-Schiff (PAS) staining and cell viability assays. Low cell growth was observed surrounding the gastric tissue on the seventh day of tissue explant culture. Cell growth subsequently increased, and at 12 days post-explant a high number of pure epithelial cells were detected. The gastric cancer cells exhibited rapid growth with a doubling time of 13-52 h, as compared to normal cells, which had a doubling time of 20-53 h. Immunocytochemical analyses of primary gastric cells revealed positive staining for cytokeratin 18 and 19, which indicated that the culture was comprised of pure epithelial cells and contained no fibroblasts. Furthermore, PAS staining demonstrated that the cultured gastric cells produced neutral mucin. Granulin and carbohydrate antigen 724 staining confirmed the purity of gastric cancer and normal cells in culture. This method of cell culture indicated that the gastric cells in primary culture consisted of mucin-secreting gastric epithelial cells, which may be useful for the study of gastric infection with Helicobacter pylori and gastric cancer.

Familial Gastric Cancers.

PubMed

Setia, Namrata; Clark, Jeffrey W; Duda, Dan G; Hong, Theodore S; Kwak, Eunice L; Mullen, John T; Lauwers, Gregory Y

2015-12-01

Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%-3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. ©AlphaMed Press.

Assessment of two methods of gastric decompression for the initial management of gastric dilatation-volvulus.

PubMed

Goodrich, Z J; Powell, L L; Hulting, K J

2013-02-01

To assess gastric trocarization and orogastric tubing as a means of gastric decompression for the initial management of gastric dilatation-volvulus. Retrospective review of 116 gastric dilatation-volvulus cases from June 2001 to October 2009. Decompression was performed via orogastric tubing in 31 dogs, gastric trocarization in 39 dogs and a combination of both in 46 dogs. Tubing was successful in 59 (75·5%) dogs and unsuccessful in 18 (23·4%) dogs. Trocarization was successful in 73 (86%) dogs and unsuccessful in 12 (14%) dogs. No evidence of gastric perforation was noted at surgery in dogs undergoing either technique. One dog that underwent trocarization had a splenic laceration identified at surgery that did not require treatment. Oesophageal rupture or aspiration pneumonia was not identified in any dog during hospitalization. No statistical difference was found between the method of gastric decompression and gastric compromise requiring surgical intervention or survival to discharge. Orogastric tubing and gastric trocarization are associated with low complication and high success rates. Either technique is an acceptable method for gastric decompression in dogs with gastric dilatation-volvulus. © 2013 British Small Animal Veterinary Association.

Beyond gastric adenocarcinoma: Multimodality assessment of common and uncommon gastric neoplasms

PubMed Central

Richman, Danielle M.; Tirumani, Sree Harsha; Hornick, Jason L.; Fuchs, Charles S.; Howard, Stephanie; Krajewski, Katherine; Ramaiya, Nikhil; Rosenthal, Michael

2016-01-01

Despite advances in molecular biology, imaging, and treatment, gastric neoplasms remain a significant cause of morbidity and mortality; gastric adenocarcinoma is the fifth most common malignancy and third most common cause of death worldwide (Brenner et al., Methods Mol Biol 472:467–477, 2009; Howson et al. Epidemiol Rev 8:1–27, 1986; Roder, Gastric Cancer 5(Suppl 1):5–11, 2002; Ferlay et al., GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. International Agency for Research on Cancer, 2013). Because of both the frequency at which malignant gastric tumors occur as well as the worldwide impact, gastric neoplasms remain important lesions to identify and characterize on all imaging modalities. Despite the varied histologies and behaviors of these neoplasms, many have similar imaging features. Nonetheless, the treatment, management, and prognosis of gastric neoplasms vary by pathology, so it is essential for the radiologist to make every effort to differentiate between these lesions and raise the less common entities as differential diagnostic considerations when appropriate. PMID:27645897

Itopride for gastric volume, gastric emptying and drinking capacity in functional dyspepsia

PubMed Central

Abid, Shahab; Jafri, Wasim; Zaman, Maseeh Uz; Bilal, Rakhshanda; Awan, Safia; Abbas, Aamir

2017-01-01

AIM To study the effect of itopride on gastric accommodation, gastric emptying and drinking capacity in functional dyspepsia (FD). METHODS Randomized controlled trial was conducted to check the effect of itopride on gastric accommodation, gastric emptying, capacity of tolerating nutrient liquid and symptoms of FD. We recruited a total of 31 patients having FD on the basis of ROME III criteria. After randomization, itopride was received by 15 patients while 16 patients received placebo. Gastric accommodation was determined using Gastric Scintigraphy. 13C labeled octanoic breadth test was performed to assess gastric emptying. Capacity of tolerating nutrient liquid drink was checked using satiety drinking capacity test. The intervention group comprised of 150 mg itopride. Patients in both arms were followed for 4 wk. RESULTS Mean age of the recruited participant 33 years (SD = 7.6) and most of the recruited individuals, i.e., 21 (67.7%) were males. We found that there was no effect of itopride on gastric accommodation as measured at different in volumes in the itopride and control group with the empty stomach (P = 0.14), at 20 min (P = 0.38), 30 min (P = 0.30), 40 min (P = 0.43), 50 min (P = 0.50), 60 min (P = 0.81), 90 min (P = 0.25) and 120 min (P = 0.67). Gastric emptying done on a sub sample (n = 11) showed no significant difference (P = 0.58) between itopride and placebo group. There was no significant improvement in the capacity to tolerate liquid in the itopride group as compared to placebo (P = 0.51). Similarly there was no significant improvement of symptoms as assessed through a composite symptom score (P = 0.74). The change in QT interval in itopride group was not significantly different from placebo (0.10). CONCLUSION Our study found no effect of itopride on gastric accommodation, gastric emptying and maximum tolerated volume in patients with FD. PMID:28217377

Gastric bypass surgery - discharge

MedlinePlus

... bypass - discharge; Gastric bypass - Roux-en-Y - discharge; Obesity gastric bypass discharge; Weight loss - gastric bypass discharge ... al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised ...

Familial Gastric Cancers

PubMed Central

Setia, Namrata; Clark, Jeffrey W.; Duda, Dan G.; Hong, Theodore S.; Kwak, Eunice L.; Mullen, John T.

2015-01-01

Although the majority of gastric carcinomas are sporadic, approximately 10% show familial aggregation, and a hereditary cause is determined in 1%–3% cases. Of these, hereditary diffuse gastric cancer is the most recognized predisposition syndrome. Although rare, the less commonly known syndromes also confer a markedly increased risk for development of gastric cancer. Identification and characterization of these syndromes require a multidisciplinary effort involving oncologists, surgeons, genetic counselors, biologists, and pathologists. This article reviews the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Implications for Practice: Although the majority of gastric adenocarcinomas are sporadic with many of those related to chronic Helicobacter pylori infection, approximately 10% of the cases show familial aggregation, and a specific hereditary cause is determined in 1%–3% cases. This review describes the molecular genetics, clinical and pathologic features, surveillance guidelines, and preventive measures of common and less common hereditary gastric cancer predisposition syndromes. Ultimately, a better understanding of the biology of these conditions should allow early identification and intervention as part of a multidisciplinary approach involving oncologists, surgeons, genetic counselors, and pathologists. PMID:26424758

Does remnant gastric cancer really differ from primary gastric cancer? A systematic review of the literature by the Task Force of Japanese Gastric Cancer Association.

PubMed

Shimada, Hideaki; Fukagawa, Takeo; Haga, Yoshio; Oba, Koji

2016-04-01

Remnant gastric cancer, most frequently defined as cancer detected in the remnant stomach after distal gastrectomy for benign disease and those cases after surgery of gastric cancer at least 5 years after the primary surgery, is often reported as a tumor with poor prognosis. The Task Force of Japanese Gastric Cancer Association for Research Promotion evaluated the clinical impact of remnant gastric cancer by systematically reviewing publications focusing on molecular carcinogenesis, lymph node status, patient survival, and surgical complications. A systematic literature search was performed using PubMed/MEDLINE with the keywords "remnant," "stomach," and "cancer," revealing 1154 relevant reports published up to the end of December 2014. The mean interval between the initial surgery and the diagnosis of remnant gastric cancer ranged from 10 to 30 years. The incidence of lymph node metastases at the splenic hilum for remnant gastric cancer is not significantly higher than that for primary proximal gastric cancer. Lymph node involvement in the jejunal mesentery is a phenomenon peculiar to remnant gastric cancer after Billroth II reconstruction. Prognosis and postoperative morbidity and mortality rates seem to be comparable to those for primary proximal gastric cancer. The crude 5-year mortality for remnant gastric cancer was 1.08 times higher than that for primary proximal gastric cancer, but this difference was not statistically significant. In conclusion, although no prospective cohort study has yet evaluated the clinical significance of remnant gastric cancer, our literature review suggests that remnant gastric cancer does not adversely affect patient prognosis and postoperative course.

Gastric cancer and family history.

PubMed

Choi, Yoon Jin; Kim, Nayoung

2016-11-01

Gastric cancer is associated with high morbidity and mortality rates worldwide. Identifying individuals at high risk is important for surveillance and prevention of gastric cancer. Having first-degree relatives diagnosed with gastric cancer is a strong and consistent risk factor for gastric cancer, but the pathogenic mechanisms behind this familial aggregation are unclear. Against this background, we reviewed the risk factors for gastric cancer in those with a first-degree relative with gastric cancer, and the possible causes for familial clustering of gastric cancer including bacterial factors, inherited genetic susceptibility, environmental factors or a combination thereof. Among individuals with a family history, current or past Helicobacter pylori infection, having two or more first-degree affected relatives or female gender was associated with an increased risk of developing gastric cancer. To date, no specific single nucleotide polymorphism has been shown to be associated with familial clustering of gastric cancer. H. pylori eradication is the most important strategy for preventing gastric cancer in first-degree relatives of gastric cancer patients, particularly those in their 20s and 30s. Early H. pylori eradication could prevent the progression to intestinal metaplasia and reduce the synergistic effect on gastric carcinogenesis in individuals with both H. pylori infection and a family history. Endoscopic surveillance is also expected to benefit individuals with a family history. Further large-scale, prospective studies are warranted to evaluate the cost-effectiveness and optimal time point for endoscopy in this population. Moreover, genome-wide association studies that incorporate environmental and dietary factors on a 'big data' basis will increase our understanding of the pathogenesis of gastric cancer.

Denervation suppresses gastric tumorigenesis

PubMed Central

Kodama, Yosuke; Muthupalani, Sureshkumar; Westphalen, Christoph B.; Andersen, Gøran T.; Flatberg, Arnar; Johannessen, Helene; Friedman, Richard A.; Renz, Bernhard W.; Sandvik, Arne K.; Beisvag, Vidar; Tomita, Hiroyuki; Hara, Akira; Quante, Michael; Li, Zhishan; Gershon, Michael D.; Kaneko, Kazuhiro; Fox, James G.; Wang, Timothy C.; Chen, Duan

2015-01-01

The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach (bilateral or unilateral truncal vagotomy, or local injection of botulinum toxin type A) markedly reduced tumor incidence and progression, but only in the denervated portion of the stomach. Vagotomy or botulinum toxin type A treatment also enhanced the therapeutic effects of systemic chemotherapy and prolonged survival. Denervation-induced suppression of tumorigenesis was associated with inhibition of Wnt signaling and suppression of stem cell expansion. In gastric organoid cultures, neurons stimulated growth in a Wnt-mediated fashion through cholinergic signaling. Furthermore, pharmacological inhibition or genetic knockout of the muscarinic acetylcholine M3 receptor suppressed gastric tumorigenesis. In gastric cancer patients, tumor stage correlated with neural density and activated Wnt signaling, whereas vagotomy reduced the risk of gastric cancer. Together, our findings suggest that vagal innervation contributes to gastric tumorigenesis via M3 receptor–mediated Wnt signaling in the stem cells, and that denervation might represent a feasible strategy for the control of gastric cancer. PMID:25143365

Proximal and Overall Gastric Emptying of Solids in Patients with Reduced Gastric Volume Accommodation Compared to Matched Controls

PubMed Central

Camilleri, Michael; Breen, Mary; Ryks, Michael; Burton, Duane

2011-01-01

Background Interventions such as gastric surgery and erythromycin result in displacement of solids to the distal stomach and acceleration of overall and proximal gastric emptying. The effect of non-surgical impairment of gastric accommodation on gastric emptying is unclear. Non-surgical impairment of gastric accommodation is associated with accelerated gastric emptying. Aim To compare measurements of proximal and overall gastric emptying in patients with reduced postprandial gastric volume accommodation with the emptying rates in age- and gender-matched controls with normal postprandial gastric volume accommodation. Methods We evaluated overall and proximal gastric emptying in 9 patients with impaired gastric accommodation and age-equivalent and gender-matched controls. Gastric volumes and emptying were measured using validated SPECT and dual gamma camera scintigraphy respectively. We compared group differences in overall and proximal gastric emptying t1/2 by t test. Results Patients with impaired postprandial gastric volume accommodation had greater fasting gastric volume. The proportion of food emptied from the proximal stomach immediately after meal ingestion was lower and t1/2of proximal gastric emptying correspondingly longer in the group with reduced postprandial gastric accommodation. In contrast, differences were not detected in overall gastric emptying in the two groups, and the ratio of overall to proximal gastric emptying t1/2was greater in the group with impaired volume accommodation. Conclusions Proximal stomach emptying is reduced in patients with impaired postprandial volume accommodation; this difference occurs predominantly during the time of meal ingestion. Compensatory mechanisms that result in normal overall gastric emptying require further elucidation. PMID:21327917

Synchronized gastric electrical stimulation improves vagotomy-induced impairment in gastric accommodation via the nitrergic pathway in dogs

PubMed Central

Chen, Jie; Koothan, Thillai; Chen, Jiande D. Z.

2009-01-01

Impaired gastric accommodation and gastric dysrhythmia are common in gastroparesis and functional dyspepsia. Recent studies have shown that synchronized gastric electrical stimulation (SGES) accelerates gastric emptying and enhances antral contractions in dogs. The aim of this study was to investigate the effects and mechanism of SGES on gastric accommodation and slow waves impaired by vagotomy in dogs. Gastric tone, compliance, and accommodation as well as slow waves with and without SGES were assessed in seven female regular dogs and seven dogs with bilateral truncal vagotomy, chronically implanted with gastric serosal electrodes and a gastric cannula. We found that 1) vagotomy impaired gastric accommodation that was normalized by SGES. The postprandial increase in gastric volume was 283.5 ± 50.6 ml in the controlled dogs, 155.2 ± 49.2 ml in the vagotomized dogs, and 304.0 ± 57.8 ml in the vagotomized dogs with SGES. The ameliorating effect of SGES was no longer observed after application of Nω-nitro-l-arginine (l-NNA); 2) vagotomy did not alter gastric compliance whereas SGES improved gastric compliance in the vagotomized dogs, and the improvement was also blocked by l-NNA; and 3) vagotomy impaired antral slow wave rhythmicity in both fasting and fed states. SGES at the proximal stomach enhanced the postprandial rhythmicity and amplitude (dominant power) of the gastric slow waves in the antrum. In conclusion, SGES with appropriate parameters restores gastric accommodation and improves gastric slow waves impaired by vagotomy. The improvement in gastric accommodation with SGES is mediated via the nitrergic pathway. Combined with previously reported findings (enhanced antral contractions and accelerated gastric emptying) and findings in this study (improved gastric accommodation and slow waves), SGES may be a viable therapy for gastroparesis. PMID:19023028

Mouse Models of Gastric Cancer

PubMed Central

Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.

2013-01-01

Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700

[Gastric perforation caused by primary gastric diffuse large B cell lymphoma].

PubMed

Kim, Ju Seok; Rou, Woo Sun; Ahn, Byung Moo; Moon, Hee Seok; Kang, Sun Hyung; Sung, Jae Kyu; Jeong, Hyun Yong; Song, Kyu-Sang

2015-01-01

Spontaneous gastric perforation is a rare complication of gastric lymphoma that is potentially life threatening since it can progress to sepsis and multi-organ failure. Morbidity also increases due to prolonged hospitalization and delay in initiating chemotherapy. Therefore prompt diagnosis and appropriate treatment is critical to improve prognosis. A 64-year-old man presented to the emergency department with severe abdominal pain. Chest X-ray showed free air below the right diaphragm. Abdominal CT scan also demonstrated free air in the peritoneal cavity with large wall defect in the lesser curvature of gastric lower body. Therefore, the patient underwent emergency operation and primary closure was done. Pathologic specimen obtained during surgery was compatible to diffuse large B cell lymphoma. Fifteen days after primary closure, the patient received subtotal gastrectomy and chemotherapy was initiated after recovery. Patient is currently being followed-up at outpatient department without any particular complications. Herein, we report a rare case of gastric lymphoma that initially presented as peritonitis because of spontaneous gastric perforation.

Gastric ulceration subsequent to partial invagination of the stomach in a dog with gastric dilatation-volvulus.

PubMed

Parton, Amanda T; Volk, Susan W; Weisse, Chick

2006-06-15

CASE DESCRIPTION-An 8-year-old castrated male German Shepherd Dog was evaluated because of abdominal distension, retching, and vomiting. CLINICAL FINDINGS-Gastric dilatation-volvulus was suspected on the basis of the dog's signalment, history, clinical signs, and results of clinicopathologic analyses and abdominal radiography. Celiotomy was performed, and gastric dilatation-volvulus was confirmed along with splenomegaly. Gastric invagination was performed over an area of gastric necrosis. The dog was reevaluated 21 days later after an episode of collapse. Findings of physical examination and clinicopathologic analyses were suggestive of internal hemorrhage. Abdominal ultrasonography and subsequent celiotomy revealed severe gastric ulceration at the gastric invagination site, splenic torsion, and a focal splenic infarct. TREATMENT AND OUTCOME-Splenectomy and gastrectomy of the necrotic tissue were performed. The dog was discharged from the hospital, and the owner was instructed to administer gastroprotectants and feed the dog a bland diet. The dog was reported to be healthy 3.25 years after surgery. CLINICAL RELEVANCE-Findings suggest that complications associated with the gastric invagination procedure include severe gastric ulceration that may require subsequent surgery. Prolonged treatment with gastroprotectants following gastric invagination surgery may be necessary to avoid gastric ulceration in dogs.

Genomic dysregulation in gastric tumors.

PubMed

Janjigian, Yelena Y; Kelsen, David P

2013-03-01

Gastric cancer is among the most common human malignancies and the second leading cause of cancer-related death. The different epidemiologic and histopathology of subtypes of gastric cancer are associated with different genomic patterns. Data suggests that gene expression patterns of proximal, distal gastric cancers-intestinal type, and diffuse/signet cell are well separated. This review summarizes the genetic and epigenetic changes thought to drive gastric cancer and the emerging paradigm of gastric cancer as three unique disease subtypes. Copyright © 2012 Wiley Periodicals, Inc.

Neonatal gastric perforation.

PubMed

Kuremu, R T; Hadley, G P; Wiersma, R

2004-01-01

Gastric perforation in neonates is a catastrophe associated with high morbidity. Most are due to underlying primary pathology. To review the management of gastric perforation in neonates in Kwa Zulu-Natal, South Africa. Retrospective study of consecutive complete data sets of neonates presenting with gastric perforation. Department of Paediatric Surgery, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa. Eight neonates treated for gastric perforation between January 1998 and April 2003. Morbidity and mortality. There was an equal number of males and females. Median birth weight was 2.0 kg with a range of 1.4 to 3.2 kg. Five of the eight neonates were premature. Primary pathologies were associated with perforation in seven of the eight neonates. Prematurity, low birth weight and pneumonia were contributing factors to the poor outcome. Sepsis was a complication in seven of the eight neonates leading to their death (88% mortality). Active perinatal management, early treatment of primary pathologies, and protection of the stomach against distension in neonates at risk are essential in the management of neonatal gastric perforation.

Effect of proton pump inhibitors on gastric juice volume, gastric pH and gastric intramucosal pH in critically ill patients : a randomized, double-blind, placebo-controlled study.

PubMed

Gursoy, Olcay; Memiş, Dilek; Sut, Necdet

2008-01-01

This study aimed to determine the effect of administration of a single-dose proton pump inhibitor (PPI) on gastric intramucosal pH (pHi), gastric juice volume and gastric pH in critically ill patients. This prospective, randomized, double-blind, placebo-controlled study included 75 patients who were divided into five groups that received the following treatment: group C (n = 15), saline 100 mL; group O (n = 15), omeprazole 20 mg; group P (n = 15), pantoprazole 40 mg; group E (n = 15), esomeprazole 20 mg; and group R (n = 15), rabeprazole 20 mg. All treatments were administered nasogastrically in 100 mL of physiological saline. Measurements of gastric pHi, gastric juice volume and gastric pH were obtained immediately before and 2, 4 and 6 hours after administration of treatments. In addition, gastric content was aspirated and its volume was recorded. Initial gastric pHi, gastric juice volume and gastric pH values were not statistically significantly different among the groups (p > 0.05). No statistically significant difference in gastric pHi was seen among the groups before or 2, 4 or 6 hours after saline or PPI administration. At hours 2, 4 and 6, gastric pH in the pantoprazole, esomeprazole and rabeprazole groups increased significantly, whereas gastric juice volume decreased significantly, compared with the omeprazole and placebo groups (p < 0.001). No statistically significant differences were seen between the pantoprazole, esomeprazole and rabeprazole groups. This is the first study to show that single-dose pantoprazole, esomeprazole and rabeprazole are associated with greater gastric pH increase and greater gastric juice volume decrease than omeprazole in critically ill patients. Our study also suggests that PPIs do not affect gastric pHi measurements in critically ill patients and can be administered during pH monitoring.

Pneumatosis in canine gastric dilatation-volvulus syndrome.

PubMed

Fischetti, Anthony J; Saunders, H Mark; Drobatz, Kenneth J

2004-01-01

Retrospectively, 243 dogs with radiographic evidence of gastric dilatation-volvulus (GDV) were studied for radiographic signs of pneumatosis (intramural gas), pneumoperitoneum, splenomegaly, and severity of gastric distention. The sensitivity, specificity, and predictive value of these imaging signs as predictors of gastric wall necrosis, as determined by visual inspection at surgery or necropsy, were determined. The sensitivity and specificity of gastric pneumatosis were 14.1% and 92.7%, respectively. The prevalence of gastric wall necrosis was 26.6%. The positive and negative predictive values of gastric pneumatosis for predicting gastric necrosis were 40.9% and 74.9%, respectively. Gastric pneumatosis and pneumoperitoneum were identified together in four dogs. Pneumoperitoneum, either alone or in conjunction with pneumatosis, yielded similar results as a test for gastric necrosis. Splenomegaly and severity of gastric distention were insensitive and nonspecific for gastric wall necrosis. Splenomegaly did not predict the need for splenectomy at surgery. Although pneumatosis and pneumoperitoneum are relatively specific signs of gastric wall necrosis, the utility of these signs as a test for gastric necrosis is limited in clinical practice. The significance of pneumatosis should be taken into consideration with previous treatments for gastric decompression, as percutaneous gastric trocharization or orogastric intubation may increase the number of false-positive results.

Gastric residual volume (GRV) and gastric contents measurement by refractometry.

PubMed

Chang, Wei-Kuo; McClave, Stephen A; Hsieh, Chung-Bao; Chao, You-Chen

2007-01-01

Traditional use of gastric residual volumes (GRVs), obtained by aspiration from a nasogastric tube, is inaccurate and cannot differentiate components of the gastric contents (gastric secretion vs delivered formula). The use of refractometry and 3 mathematical equations has been proposed as a method to calculate the formula concentration, GRV, and formula volume. In this paper, we have validated these mathematical equations so that they can be implemented in clinical practice. Each of 16 patients receiving a nasogastric tube had 50 mL of water followed by 100 mL of dietary formula (Osmolite HN, Abbott Laboratories, Columbus, OH) infused into the stomach. After mixing, gastric content was aspirated for the first Brix value (BV) measurement by refractometry. Then, 50 mL of water was infused into the stomach and a second BV was measured. The procedure of infusion of dietary formula (100 mL) and then water (50 mL) was repeated and followed by subsequent BV measurement. The same procedure was performed in an in vitro experiment. Formula concentration, GRV, and formula volume were calculated from the derived mathematical equations. The formula concentrations, GRVs, and formula volumes calculated by using refractometry and the mathematical equations were close to the true values obtained from both in vivo and in vitro validation experiments. Using this method, measurement of the BV of gastric contents is simple, reproducible, and inexpensive. Refractometry and the derived mathematical equations may be used to measure formula concentration, GRV, and formula volume, and also to serve as a tool for monitoring the gastric contents of patients receiving nasogastric feeding.

Serum and gastric fluid levels of cytokines and nitrates in gastric diseases infected with Helicobacter pylori.

PubMed

Mehmet, N; Refik, M; Harputluoglu, M; Ersoy, Y; Aydin, N Engin; Yildirim, B

2004-04-01

This case control study presents data on the concentrations of nitrite and nitrate and a variety of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor TNF-alpha in gastric fluid and serum. Patients with gastritis, gastric ulcer and gastric cancer are studied and grouped according to infection by Helicobacter pylori. The 208 patients who underwent upper gastrointestinal endoscopic examination were classified as follows; H. pylori-positive gastritis (n = 32), H. pylori-negative gastritis (n = 32), H. pylori-positive ulcers (n = 34), H. pylori-negative ulcers (n = 34), 43 patients with H. pylori-positive gastric cancer in addition to 33 H. pylori-negative healthy control individuals. Gastric fluids and blood samples were taken concomitantly. Cytokines and nitrite and nitrate determinations were attempted as soon as possible after collection of the samples. Nitrite and nitrate levels of serum and gastric fluids of H. pylori-positive gastritis and ulcers were higher than H. pylori-negative gastritis and ulcers. The concentrations of total nitrite and nitrate and cytokines (TNF-alpha, IL-2R, IL-6, and IL-8) in gastric fluids and sera of H. pylori-positive gastric cancer patients were higher than H. pylori-negative control groups. IL-1 beta level was significantly elevated in gastric fluid of infected cancer patients but not in serum. Taken together, the results suggest that an increase in cytokine-NO combination in gastric mucosa previously reported by many studies is not restricted to local infected gastric tissue but also detected in gastric fluid and sera of H. pylori-positive subjects and may have an important role in the pathogenesis and development of common gastric diseases.

Current molecular markers for gastric progenitor cells and gastric cancer stem cells.

PubMed

Qiao, Xiaotan T; Gumucio, Deborah L

2011-07-01

Gastric stem and progenitor cells (GPC) play key roles in the homeostatic renewal of gastric glands and are instrumental in epithelial repair after injury. Until very recently, the existence of GPC could only be inferred by indirect labeling strategies. The last few years have seen significant progress in the identification of biomarkers that allow prospective identification of GPC. The analysis of these unique cell populations is providing new insights into the molecular underpinnings of gastric epithelial homeostasis and repair. Of closely related interest is the potential to identify so-called cancer stem cells, a rare subpopulation of tumor-initiating cells. Here, we review the current useful biomarkers for GPC, including: (a) those that have been demonstrated by lineage tracing to give rise to all gastric cell lineages (e.g., the villin-transgene marker as well as Lgr5); (b) those that give rise to a subset of gastric lineages (e.g., TFF2); (c) markers that recognize cryptic progenitors for metaplasia (e.g., MIST1), and (d) markers that have not yet been analyzed by lineage tracing (e.g., DCKL1/DCAMKL1, CD133/PROM1, and CD44). The study of these markers has been mostly limited to the mouse model, but the hope is that the rapid pace of recent breakthroughs in this animal model will soon lead to a greater understanding of human gastric stem cell biology and to new insights into gastric cancer, the second leading cause of cancer-related death worldwide.

Pathogenesis of NSAID-induced gastric damage: Importance of cyclooxygenase inhibition and gastric hypermotility

PubMed Central

Takeuchi, Koji

2012-01-01

This article reviews the pathogenic mechanism of non-steroidal anti-inflammatory drug (NSAID)-induced gastric damage, focusing on the relation between cyclooxygenase (COX) inhibition and various functional events. NSAIDs, such as indomethacin, at a dose that inhibits prostaglandin (PG) production, enhance gastric motility, resulting in an increase in mucosal permeability, neutrophil infiltration and oxyradical production, and eventually producing gastric lesions. These lesions are prevented by pretreatment with PGE2 and antisecretory drugs, and also via an atropine-sensitive mechanism, not related to antisecretory action. Although neither rofecoxib (a selective COX-2 inhibitor) nor SC-560 (a selective COX-1 inhibitor) alone damages the stomach, the combined administration of these drugs provokes gastric lesions. SC-560, but not rofecoxib, decreases prostaglandin E2 (PGE2) production and causes gastric hypermotility and an increase in mucosal permeability. COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib. The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility. In addition, selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions, including adrenalectomy, arthritis, and Helicobacter pylori-infection. In summary, gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage, and the response, causally related with PG deficiency due to COX-1 inhibition, occurs prior to other pathogenic events such as increased mucosal permeability; and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2, the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility, and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition. PMID:22611307

A gastric acid secretion model.

PubMed Central

de Beus, A M; Fabry, T L; Lacker, H M

1993-01-01

A theory of gastric acid production and self-protection is formulated mathematically and examined for clinical and experimental correlations, implications, and predictions using analytic and numerical techniques. In our model, gastric acid secretion in the stomach, as represented by an archetypal gastron, consists of two chambers, circulatory and luminal, connected by two different regions of ion exchange. The capillary circulation of the gastric mucosa is arranged in arterial-venous arcades which pass from the gastric glands up to the surface epithelial lining of the lumen; therefore the upstream region of the capillary chamber communicates with oxyntic cells, while the downstream region communicates with epithelial cells. Both cell types abut the gastric lumen. Ion currents across the upstream region are calculated from a steady-state oxyntic cell model with active ion transport, while the downstream ion fluxes are (facilitated) diffusion driven or secondarily active. Water transport is considered iso-osmotic. The steady-state model is solved in closed form for low gastric lumen pH. A wide variety of previously performed static and dynamic experiments on ion and CO2 transport in the gastric lumen and gastric blood supply are for the first time correlated with each other for an (at least) semiquantitative test of current concepts of gastric acid secretion and for the purpose of model verification. Agreement with the data is reported with a few outstanding and instructive exceptions. Model predictions and implications are also discussed. Images FIGURE 1 PMID:8396457

The role of perioperative chewing gum on gastric fluid volume and gastric pH: a meta-analysis.

PubMed

Ouanes, Jean-Pierre P; Bicket, Mark C; Togioka, Brandon; Tomas, Vicente Garcia; Wu, Christopher L; Murphy, Jamie D

2015-03-01

To determine if preoperative gum chewing affects gastric pH and gastric fluid volume. Systematic review and meta-analysis. Data sources included Cochrane, PubMed, and EMBASE databases from inception to June 2012 and reference lists of known relevant articles without language restriction. Randomized controlled trials in which a treatment group that chewed gum was compared to a control group that fasted were included. Relevant data, including main outcomes of gastric fluid volume and gastric pH, were extracted. Four studies involving 287 patients were included. The presence of chewing gum was associated with small but statically significant increases in gastric fluid volume (mean difference = 0.21 mL/kg; 95% confidence interval, 0.02-0.39; P = .03) but not in gastric pH (mean difference = 0.11 mL/kg; 95% confidence interval, -0.14 to 0.36; P = .38). Gastric fluid volume and gastric pH remained unchanged in subgroup analysis by either sugar or sugarless gum type. Chewing gum in the perioperative period causes small but statically significant increases in gastric fluid volume and no change in gastric pH. The increase in gastric fluid most likely is of no clinical significance in terms of aspiration risk for the patient. Elective surgery should not necessarily be canceled or delayed in healthy patients who accidentally chew gum preoperatively. Copyright © 2014 Elsevier Inc. All rights reserved.

Malignant gastric lymphoma with spontaneous perforation.

PubMed

Shimada, Satoko; Gen, Tokichi; Okamoto, Hiroyuki

2013-01-17

Malignant gastric lymphoma, accounting only for 1% of primary gastric carcinoma, is usually a diffuse large B-cell lymphoma. Toyota et al reported that 37% of gastric perforations involved malignancy, generally gastric carcinoma. Fukuda et al found that less than 5% of malignant gastric lymphomas perforate. While it is relatively well known that perforations often take place during chemotherapy, they are rare in patients not receiving chemotherapy. To our knowledge, spontaneous perforation is rare in gastric malignant lymphoma, having been reported in the Japanese literature only 26 times, including this case, in the last 25 years.

Effects of remifentanil on gastric tone.

PubMed

Walldén, Jakob; Thörn, Sven-Egron; Lindberg, Greger; Wattwil, Magnus

2008-08-01

Opioids are well known for impairing gastric motility. The mechanism is far from clear and there is wide interindividual variability. The purpose of this study was to evaluate the effect of remifentanil on proximal gastric tone. Healthy volunteers were studied on two occasions and proximal gastric tone was measured by a gastric barostat. On the first occasion (n=8), glucagon 1 mg IV was given as a reference for a maximal relaxation of the stomach. On the second occasion (n=9), remifentanil was given in incremental doses (0.1, 0.2 and 0.3 microg/kg/min) for 15 min each, followed by a washout period of 30 min. Thereafter, remifentanil was readministered, and 10 min later glucagon 1 mg was given. Mean intragastric bag volumes were calculated for each 5-min interval. Glucagon decreased gastric tone in all subjects. Remifentanil had a marked effect on gastric tone; we found two distinct patterns of reactions with both increases and decreases in gastric tone and, during the remifentanil infusion, glucagon did not affect gastric tone. Remifentanil induced changes in gastric tone with both increases and decreases. The effect of remifentanil on gastric tone is probably dependent on the current state of the systems involved.

[Eleven Patients with Gastric Cancer Who Received Chemotherapy after Stent Placement for Gastric Outlet Obstruction].

PubMed

Endo, Shunji; Nakagawa, Tomo; Konishi, Ken; Ikenaga, Masakazu; Ohta, Katsuya; Nakashima, Shinsuke; Matsumoto, Kenichi; Nishikawa, Kazuhiro; Ohmori, Takeshi; Yamada, Terumasa

2017-01-01

Endoscopic placement of self-expandable metallic stents is reportedly effective for gastric outlet obstructions due to advanced gastric cancer, and is less invasive than gastrojejunostomy. For patients who have good performance status, we administer chemotherapy after stent placement, although the safety and feasibility of this chemotherapy have not yet been discussed in full. Between 2011 and 2015, 15 patients at our institution underwent endoscopic gastroduodenal stent placement for gastric outlet obstruction due to gastric cancer. Eleven of these patients were administered chemotherapy after stent placement. In our case series, we did not observe any specific adverse event caused by stent placement plus chemotherapy. Adverse events after chemotherapy included anemia of CTCAE Grade 3 in 7 patients. Stent-in-stent placement was needed in 2 patients. Neither stent migration nor perforation was observed. Therefore, chemotherapy after stent placement for gastric outlet obstruction due to gastric cancer was considered safe and feasible. Stent placement is useful not only as palliative care for patients with terminal-stage disease, but also as one of the multimodal therapeutic strategies for gastric cancer.

Gastric metastasis from invasive lobular breast cancer, mimicking primary gastric cancer: A case report.

PubMed

Kim, Dae Hoon; Son, Seung-Myoung; Choi, Young Jin

2018-03-01

Gastric metastasis from invasive lobular breast cancer is relatively rare, commonly presented among multiple metastases, several years after primary diagnosis of breast cancer. Importantly, gastric cancer that is synchronously presented with lobular breast cancer can be misdiagnosed as primary gastric cancer; therefore, accurate differential diagnosis is required. A 39-year-old woman was visited to our hospital because of right breast mass and progressive dyspepsia. Invasive lobular carcinoma of breast was diagnosed on core needle biopsy. Gastroscopy revealed a diffuse scirrhous mass at the prepyloric antrum and diagnosed as poorly differentiated adenocarcinoma on biopsy. Synchronous double primary breast and gastric cancers were considered. Detailed pathological analysis focused on immunohistochemical studies of selected antibodies, including those of estrogen receptors, gross cystic disease fluid protein-15, and caudal-type homeobox transcription factor 2, were studied. As a result, gastric lesion was diagnosed as metastatic gastric cancer originating from breast. Right breast conserving surgery was performed, and duodenal stent was inserted under endoscopic guidance to relieve the patient's symptoms. Systemic chemotherapy with combined administration of paclitaxel and trastuzumab was initiated. Forty-one months after the diagnosis, the patient is still undergoing the same therapy. No recurrent lesion has been identified in the breast and evidence of a partial remission of gastric wall thickening has been observed on follow-up studies without new metastatic lesions. Clinical suspicion, repeat endoscopic biopsy, and detailed histological analysis, including immunohistochemistry, are necessary for diagnosis of metastatic gastric cancer from the breast.

Hypermethylation of the TSLC1 Gene Promoter in Primary Gastric Cancers and Gastric Cancer Cell Lines

PubMed Central

Honda, Teiichiro; Waki, Takayoshi; Jin, Zhe; Sato, Kiyoshi; Motoyama, Teiichi; Kawata, Sumio; Kimura, Wataru; Nishizuka, Satoshi; Murakami, Yoshinori

2002-01-01

The TSLC1 (tumor suppressor in lung cancer–1) gene is a novel tumor suppressor gene on chromosomal region 11q23.2, and is frequently inactivated by concordant promoter hypermethylation and loss of heterozygosity (LOH) in non‐small cell lung cancer (NSCLC). Because LOH on 11q has also been observed frequently in other human neoplasms including gastric cancer, we investigated the promoter methylation status of TSLC1 in 10 gastric cancer cell lines and 97 primary gastric cancers, as well as the corresponding non‐cancerous gastric tissues, by bisulfite‐SSCP analysis followed by direct sequencing. Allelic status of the TSLC1 gene was also investigated in these cell lines and primary gastric cancers. The TSLC1 promoter was methylated in two gastric cancer cell lines, KATO‐III and ECC10, and in 15 out of 97 (16%) primary gastric cancers. It was not methylated in non‐cancerous gastric tissues, suggesting that this hypermethylation is a cancer‐specific alteration. KATO‐III and ECC10 cells retained two alleles of TSLC1, both of which showed hypermethylation, associated with complete loss of gene expression. Most of the primary gastric cancers with promoter methylation also retained heterozygosity at the TSLC1 locus on 11q23.2. These data indicate that bi‐allelic hypermethylation of the TSLC1 promoter and resulting gene silencing occur in a subset of primary gastric cancers. PMID:12716461

Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms.

PubMed

Kim, Young Beak; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

2016-03-01

Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.

Clinical epidemiology of gastric cancer in Hehuang valley of China: A 10-year epidemiological study of gastric cancer

PubMed Central

Yan, Su; Li, Bin; Bai, Zhen-Zhong; Wu, Jun-Qi; Xie, Da-Wei; Ma, Ying-Cai; Ma, Xu-Xiang; Zhao, Jun-Hui; Guo, Xin-Jian

2014-01-01

AIM: To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley, China, to provide a reference for treatment and prevention of regional gastric cancer. METHODS: Between February 2003 and February 2013, the records of 2419 patients with gastric cancer were included in this study. The patient’s characteristics, histological and pathological features, as well as the dietary habits of the patients, were investigated. RESULTS: The clinical data showed that adenocarcinoma was the leading histological type of gastric cancer in this area. Characteristics of gastric cancer in different ethnic groups and age showed that the 60.55-65.50 years group showed the high incidence of gastric cancer in all ethnic groups. There were more male gastric cancer patients than female. Intestinal was the most common type of gastric cancer in the Hehuang valley. There was no significant difference in the proportion of sex in terms of Helicobacter pylori infection. The impact of dietary habits on gastric cancer showed that regular consumption of fried or grilled food, consumption of high-salt, high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females. CONCLUSION: Differences existed in race, sex, and age of patients according to the epidemiology of gastric cancer in the Hehuang valley. Moreover, dietary habits was also an important factor contributing to gastric cancer. PMID:25132766

MYC and gastric adenocarcinoma carcinogenesis

PubMed Central

Calcagno, Danielle Queiroz; Leal, Mariana Ferreira; Assumpção, Paulo Pimentel; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodríguez

2008-01-01

MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacter pylori (H pylori) and clinical applications. PMID:18932273

Computed tomography findings of acute gastric volvulus.

PubMed

Millet, Ingrid; Orliac, Celine; Alili, Chakib; Guillon, Françoise; Taourel, Patrice

2014-12-01

To assess the diagnostic performance of CT signs of gastric volvulus in both confirmed cases and control subjects. We retrospectively reviewed CT findings in 10 patients with surgically confirmed acute gastric volvulus and 20 control subjects with gastric distension. Two radiologists independently evaluated CT images for risk factors of gastric volvulus, direct findings of gastric volvulus by assessing gastric dilatation, the presence of an antropyloric transition point, the respective position of the different stomach segments and of the greater and lesser curvatures, stenosis of the gastric segments through the oesophageal hiatus and for findings of gastric ischemia. The sensitivity and specificity of each finding were calculated. The most sensitive direct signs of gastric volvulus were an antropyloric transition point without any abnormality at the transition zone and the antrum at the same level or higher than the fundus. The presence of both these two findings as diagnostic criteria of gastric volvulus had 100% sensitivity and specificity for the diagnosis of gastric volvulus. There was no association between CT signs of ischemia and final bowel ischemia at pathology. CT is both highly sensitive and specific for diagnosing acute gastric volvulus. CT is highly reliable for diagnosing acute gastric volvulus with two findings. The two signs are gastropyloric transition zone and abnormal location of the antrum. This allows fast surgical management of this emergency.

A novel approach for the detection of early gastric cancer: fluorescence spectroscopy of gastric juice.

PubMed

Deng, Kai; Zhou, Li Ya; Lin, San Ren; Li, Yuan; Chen, Mo; Geng, Qiu Ming; Li, Yu Wen

2013-06-01

This study aimed to investigate the efficacy of fluorescence spectroscopy of gastric juice for early gastric cancer (EGC) screening. Gastric juice was collected from 101 participants who underwent endoscopy in the Outpatient Endoscopy Center of Peking University Third Hospital. The participants were divided into three groups: the normal mucosa or chronic non-atrophic gastritis (NM-CNAG) group (n = 35), advanced gastric cancer (AGC) group (n = 33) and EGC group (n = 33). Fluorescence spectroscopic analysis was performed in all the gastric juice samples and the maximum fluorescence intensity of the first peak (P1 FI) was measured. The mean fluorescence intensity of P1 FI of gastric juice in AGC (92.1 ± 10.7) and EGC (90.8 ± 12.0) groups was significantly higher than that in the NM-CNAG group (55.7 ± 7.5) (AGC vs NM-CNAG, P = 0.006 and EGC vs NM-CNAG, P = 0.015, respectively). The areas under the receiver operating characteristic curves for the detection of AGC and EGC were 0.681 (95% confidence interval [CI] 0.553-0.810, P = 0.010) and 0.655 (95% CI 0.522-0.787, P = 0.028). With the P1 FI of ≥47.7, the sensitivity, specificity and accuracy for detecting EGC were 69.7%, 57.1% and 63.2%, respectively. The enhancement of P1 FI of gastric juice occurs at the early stage of gastric cancer. Fluorescence spectroscopy of gastric juice may be used as a novel screening tool for the early detection of gastric cancer. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

Customization of laparoscopic gastric devascularization and splenectomy for gastric varices based on CT vascular anatomy.

PubMed

Kawanaka, Hirofumi; Akahoshi, Tomohiko; Nagao, Yoshihiro; Kinjo, Nao; Yoshida, Daisuke; Matsumoto, Yoshihiro; Harimoto, Norifumi; Itoh, Shinji; Yoshizumi, Tomoharu; Maehara, Yoshihiko

2018-01-01

Laparoscopic gastric devascularization(Lap GDS) and splenectomy (SPL) for gastric varices is technically challenging because of highly developed collateral vessels and bleeding tendency. We investigated the feasibility of customization of Lap GDS and SPL based on CT vascular anatomy. We analyzed 61 cirrhotic patients with gastric varices who underwent Lap GDS and SPL between 2006 and 2014. Lap GDS was customized according to the afferent feeding veins (left gastric vein (LGV) and/or posterior gastric vein (PGV)/short gastric vein (SGV)) and efferent drainage veins (gastrorenal shunt and/or gastrophrenic shunt, or numerous retroperitoneal veins) based on CT imaging. Thirty-four patients with efferent drainage veins suitable for balloon-occluded retrograde transvenous obliteration (B-RTO) underwent B-RTO instead of surgical GDS, with subsequent Lap SPL. Among 27 patients with gastric varices unsuitable for B-RTO, 15 patients with PGV/SGV underwent Lap GDS of the greater curvature and SPL, and 12 patients with LGV or LGV/PGV/SGV underwent Lap GDS of the greater and lesser curvature and SPL. The mean operation time was 294 min and mean blood loss was 198 g. There was no mortality or severe morbidity. Gastric varices were eradicated in all 61 patients, with no bleeding or recurrence during a mean follow-up of 55.9 months. The cumulative 3-, 5-, and 7-year survival rates were 92, 82, and 64%, respectively. Lap GDS and SPL customized based on CT vascular anatomy is a safe and effective procedure for treating gastric varices.

Molecular biology of gastric cancer.

PubMed

Cervantes, A; Rodríguez Braun, E; Pérez Fidalgo, A; Chirivella González, I

2007-04-01

Despite its decreasing incidence overall, gastric cancer is still a challenging disease. Therapy is based mainly upon surgical resection when the tumour remains localised in the stomach. Conventional chemotherapy may play a role in treating micrometastatic disease and is effective as palliative therapy for recurrent or advanced disease. However, the knowledge of molecular pathways implicated in gastric cancer pathogenesis is still in its infancy and the contribution of molecular biology to the development of new targeted therapies in gastric cancer is far behind other more common cancers such as breast, colon or lung. This review will focus first on the difference of two well defined types of gastric cancer: intestinal and diffuse. A discussion of the cell of origin of gastric cancer with some intriguing data implicating bone marrow derived cells will follow, and a comprehensive review of different genetic alterations detected in gastric cancer, underlining those that may have clinical, therapeutic or prognostic implications.

Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms

PubMed Central

Kim, Young Beak; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

2016-01-01

Background/Aims Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. Methods Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. Results In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). Conclusions The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma. PMID:26087787

Nutrients affecting gastric barrier.

PubMed

Gasbarrini, Antonio; D'Aversa, Francesca; Di Rienzo, Teresa; Franceschi, Francesco

2014-01-01

The gastric barrier could be considered an active tissue involved in many synthetic and metabolic functions, as the immunological defense, by activating mucosal immune system. Barrier integrity results from a balance between protective and aggressive endogenous factors and from their interaction with exogenous factors (steroidal or nonsteroidal anti-inflammatory drugs, dietary nitrates, nitrites and/or NaCl, stress, Helicobacter pylori infection, food allergens and contaminants, metals, chemicals, radiation, smoking and alcohol intake). Nutrients represent the most important exogenous factors affecting gastric barrier because of the impact on people's everyday life. We report evidence from the literature about nutrients affecting gastric barrier and we investigate the possible effect that nutrients can play to determining or maintaining a gastric barrier dysfunction. © 2014 S. Karger AG, Basel.

Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer.

PubMed

Yang, Yunben; Shao, Yongfu; Zhu, Mengying; Li, Qier; Yang, Fang; Lu, Xuwen; Xu, Chunjing; Xiao, Bingxiu; Sun, Yanke; Guo, Junming

2016-01-01

Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.

Redefining early gastric cancer.

PubMed

Barreto, Savio G; Windsor, John A

2016-01-01

The problem is that current definitions of early gastric cancer allow the inclusion of regional lymph node metastases. The increasing use of endoscopic submucosal dissection to treat early gastric cancer is a concern because regional lymph nodes are not addressed. The aim of the study was thus to critically evaluate current evidence with regard to tumour-specific factors associated with lymph node metastases in "early gastric cancer" to develop a more precise definition and improve clinical management. A systematic and comprehensive search of major reference databases (MEDLINE, EMBASE, PubMed and the Cochrane Library) was undertaken using a combination of text words "early gastric cancer", "lymph node metastasis", "factors", "endoscopy", "surgery", "lymphadenectomy" "mucosa", "submucosa", "lymphovascular invasion", "differentiated", "undifferentiated" and "ulcer". All available publications that described tumour-related factors associated with lymph node metastases in early gastric cancer were included. The initial search yielded 1494 studies, of which 42 studies were included in the final analysis. Over time, the definition of early gastric cancer has broadened and the indications for endoscopic treatment have widened. The mean frequency of lymph node metastases increased on the basis of depth of infiltration (mucosa 6% vs. submucosa 28%), presence of lymphovascular invasion (absence 9% vs. presence 53%), tumour differentiation (differentiated 13% vs. undifferentiated 34%) and macroscopic type (elevated 13% vs. flat 26%) and tumour diameter (≤2 cm 8% vs. >2 cm 25%). There is a need to re-examine the diagnosis and staging of early gastric cancer to ensure that patients with one or more identifiable risk factor for lymph node metastases are not denied appropriate chemotherapy and surgical resection.

Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer.

PubMed

Jencks, David S; Adam, Jason D; Borum, Marie L; Koh, Joyce M; Stephen, Sindu; Doman, David B

2018-02-01

Gastric intestinal metaplasia is a precancerous change of the mucosa of the stomach with intestinal epithelium, and is associated with an increased risk of dysplasia and cancer. The pathogenesis to gastric cancer is proposed by the Correa hypothesis as the transition from normal gastric epithelium to invasive cancer via inflammation followed by intramucosal cancer and invasion. Multiple risk factors have been associated with the development of gastric intestinal metaplasia interplay, including Helicobacter pylori infection and associated genomics, host genetic factors, environmental milieu, rheumatologic disorders, diet, and intestinal microbiota. Globally, screening guidelines have been established in countries with high incidence. In the United States, no such guidelines have been developed due to lower, albeit increasing, incidence. The American Society for Gastrointestinal Endoscopy recommends a case-by-case patient assessment based upon epidemiology, genetics, and environmental risk factors. Studies have examined the use of a serologic biopsy to stratify risk based upon factors such as H pylori status and virulence factors, along with serologic markers of chronic inflammation including pepsinogen I, pepsinogen II, and gastrin. High-risk patients may then be advised to undergo endoscopic evaluation with mapping biopsies from the antrum (greater curvature, lesser curvature), incisura angularis, and corpus (greater curvature, lesser curvature). Surveillance guidelines have not been firmly established for patients with known gastric intestinal metaplasia, but include repeat endoscopy at intervals according to the histologic risk for malignant transformation.

[Gastric magnetic resonance study (methods, semiotics)].

PubMed

Stashuk, G A

2003-01-01

The paper shows the potentialities of gastric study by magnetic resonance imaging (MRI). The methodic aspects of gastric study have been worked out. The MRI-semiotics of the unchanged and tumor-affected wall of the stomach and techniques in examining patients with gastric cancer of various sites are described. Using the developed procedure, MRI was performed in 199 patients, including 154 patients with gastric pathology and 45 control individuals who had no altered gastric wall. Great emphasis is placed on the role of MRI in the diagnosis of endophytic (diffuse) gastric cancer that is of priority value in its morphological structure. MRI was found to play a role in the diagnosis of the spread of a tumorous process both along the walls of the stomach and to its adjacent anatomic structures.

Stomach (Gastric) Cancer—Health Professional Version

Cancer.gov

Almost all gastric cancers are adenocarcinomas. Other types of gastric cancer are gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, and lymphomas. Find evidence-based information on gastric cancer treatment, causes and prevention, screening, research, and statistics.

Unconvincing diagnosis of a rare subtype of primary gastric lymphoma with incongruent endoscopic presentation: a case of gastric schwannoma.

PubMed

Lee, Seung Soo; Kim, In Ho

2013-12-01

Primary gastric lymphoma is a rare gastric malignancy. Its diagnostic process is complex. Clinician may find initial diagnosis of primary gastric lymphoma unreliable, especially when it indicates the rarest subtype of gastric lymphoma, while its initial endoscopic presentation fails to raise the slightest suspicion of primary gastric lymphoma. A 53-year-old Korean man was diagnosed, by endoscopic examination, with a round submucosal tumor of the stomach. Deep endoscopic biopsy, however, confirmed CD5 positive gastric lymphoma. Surgical treatment was performed for diagnosis and treatment. Postoperative histo-logical examination confirmed gastric schwannoma. Gastric schwannoma is a spindle cell tumor, characterized by a peripheral cuff-like lymphocytic infiltration. Deep endoscopic biopsy may have been misdirected to the peripheral lymphoid cuff, failing to acquire spindle cells. The literature has been reviewed, and options for diagnostic accuracy have been suggested.

Systematic alphanumeric-coded endoscopy versus chromoendoscopy for the detection of precancerous gastric lesions and early gastric cancer in subjects at average risk for gastric cancer.

PubMed

Pérez-Mendoza, A; Zárate-Guzmán, Á M; Galvis García, E S; Sobrino Cossío, S; Djamus Birch, J

Gastric cancer is one of the main causes of cancer worldwide, but there is currently no global screening strategy for the disease. Endoscopy is the screening method of choice in some Asian countries, but no standardized technique has been recognized. Systematic alphanumeric-coded endoscopy can increase gastric lesion detection. The aim of the present article was to compare the usefulness of systematic alphanumeric-coded endoscopy with conventional endoscopy for the detection of premalignant lesions and early gastric cancer in subjects at average risk for gastric cancer. A cross-sectional, comparative, prospective, randomized study was conducted on patients at average risk for gastric cancer (40-50 years of age, no history of H. pylori infection, intestinal metaplasia, gastric atrophy, or gastrointestinal surgery). Before undergoing endoscopy, the patients had gastric preparation (200mg of oral acetylcysteine or 50mg of oral dimethicone). Conventional chromoendoscopy was performed with indigo carmine dye for contrast enhancement. Fifty consecutive cases (mean age 44.4 ± 3.34 years, 60% women, BMI 27.6 ± 5.82 kg/m 2 ) were evaluated. Endoscopic imaging quality was satisfactory in all the cases, with no differences between methods (p = 0.817). The detection rate of premalignant lesions and early gastric cancer was 14% (6 cases of intestinal metaplasia and one case of gastric adenocarcinoma). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 100, 95, 80, 100 and 96%, respectively, for systematic alphanumeric-coded endoscopy, and 100, 45, 20, 100, and 52%, respectively, for conventional endoscopy. Lesion detection through systematic alphanumeric-coded endoscopy was superior to that of conventional endoscopy (p = 0.003; OR = 12). Both techniques were effective, but systematic alphanumeric-coded endoscopy significantly reduced the false positive rate. Copyright © 2018 Asociación Mexicana de

Management of Gastric Obstruction Caused by Adjustable Gastric Band.

PubMed

Czeiger, David; Abu-Swis, Shadi; Shaked, Gad; Ovnat, Amnon; Sebbag, Gilbert

2016-12-01

Optimal adjustment of the filling volume of laparoscopic adjustable gastric banding is challenging and commonly performed empirically. Patients with band over-inflation and gastric obstruction arrive at the emergency department complaining of recurrent vomiting. In cases of gastric obstruction, intra-band pressure measurement may assist in determining the amount of fluid that should be removed from the band; however, our investigations have determined that intra-band pressure assessment need not play a role in the treatment of gastric band obstruction. In patients coming to the emergency department with gastric band obstruction, we measured intra-band pressure at arrival and following stepped removal of fluid, comparing the initial pressure with post-deflation pressure and measuring the volume of fluid removed. Forty-eight patients participated in the study. Forty-five patients had a low-pressure/high-volume band. Their mean baseline pressure was 54.6 ± 22.3 mmHg. The mean volume of fluid removed from the band was 1.3 ± 0.8 ml. The mean post-deflation pressure was 22.5 ± 16.3 mmHg. Nearly 30 % of patients required as little as 0.5 ml of fluid removal, and 60 % of them were free of symptoms with removal of 1 ml. Our results indicate that intra-band pressure measurement is of little value for determining the amount of fluid that should be removed for treatment of band obstruction. We suggest the removal of fluid in volumes of 0.5 ml until symptoms are relieved. Only in complicated cases, such as in patients having recurrent obstructions, should additional modalities be employed for further management guidance.

DBGC: A Database of Human Gastric Cancer

PubMed Central

Wang, Chao; Zhang, Jun; Cai, Mingdeng; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

2015-01-01

The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated into the DBGC. We believe that this database will greatly facilitate research regarding human gastric cancer in many fields. DBGC is freely available at http://bminfor.tongji.edu.cn/dbgc/index.do PMID:26566288

Characterization of Gastric Microbiota in Twins.

PubMed

Dong, Quanjiang; Xin, Yongning; Wang, Lili; Meng, Xinying; Yu, Xinjuan; Lu, Linlin; Xuan, Shiying

2017-02-01

Contribution of host genetic backgrounds in the development of gastric microbiota has not been clearly defined. This study was aimed to characterize the biodiversity, structure and composition of gastric microbiota among twins. A total of four pairs of twins and eight unrelated individuals were enrolled in the study. Antral biopsies were obtained during endoscopy. The bacterial 16S rRNA gene was amplified and pyrosequenced. Sequences were analyzed for the composition, structure, and α and β diversities of gastric microbiota. Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria were the most predominant phyla of gastric microbiota. Each individual, twins as well as unrelated individuals, harbored a microbiota of distinct composition. There was no evidence of additional similarity in the richness and evenness of gastric microbiota among co-twins as compared to unrelated individuals. Calculations of θ YC and PCoA demonstrated that the structure similarity of gastric microbial community between co-twins did not increase compared to unrelated individuals. In contrast, the structure of microbiota was altered enormously by Helicobacter pylori infection. These results suggest that host genetic backgrounds had little effect in shaping the gastric microbiota. This property of gastric microbiota could facilitate the studies discerning the role of microbiota from genetic grounds in the pathogenesis.

Gastric cancer stem cells: A novel therapeutic target

PubMed Central

Singh, Shree Ram

2013-01-01

Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

Gastric carcinoma originating from the heterotopic submucosal gastric gland treated by laparoscopy and endoscopy cooperative surgery

PubMed Central

Imamura, Taisuke; Komatsu, Shuhei; Ichikawa, Daisuke; Kobayashi, Hiroki; Miyamae, Mahito; Hirajima, Shoji; Kawaguchi, Tsutomu; Kubota, Takeshi; Kosuga, Toshiyuki; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Ogiso, Kiyoshi; Yagi, Nobuaki; Yanagisawa, Akio; Ando, Takashi; Otsuji, Eigo

2015-01-01

Gastric carcinoma is derived from epithelial cells in the gastric mucosa. We reported an extremely rare case of submucosal gastric carcinoma originating from the heterotopic submucosal gastric gland (HSG) that was safely diagnosed by laparoscopy and endoscopy cooperative surgery (LECS). A 66-year-old man underwent gastrointestinal endoscopy, which detected a submucosal tumor (SMT) of 1.5 cm in diameter on the lesser-anterior wall of the upper gastric body. The tumor could not be diagnosed histologically, even by endoscopic ultrasound-guided fine-needle aspiration biopsy. Local resection by LECS was performed to confirm a diagnosis. Pathologically, the tumor was an intra-submucosal well differentiated adenocarcinoma invading 5000 μm into the submucosal layer. The resected tumor had negative lateral and vertical margins. Based on the Japanese treatment guidelines, additional laparoscopic proximal gastrectomy was curatively performed. LECS is a less invasive and safer approach for the diagnosis of SMT, even in submucosal gastric carcinoma originating from the HSG. PMID:26306144

Occupation and gastric cancer

PubMed Central

Raj, A; Mayberry, J; Podas, T

2003-01-01

Gastric cancer is a cause of significant morbidity and mortality. There are several risk factors, with occupation emerging as one of these. There is considerable evidence that occupations in coal and tin mining, metal processing, particularly steel and iron, and rubber manufacturing industries lead to an increased risk of gastric cancer. Other "dusty" occupations—for example, wood processing, or work in high temperature environments have also been implicated but the evidence is not strong. The mechanism of pathogenesis of gastric cancer is unclear and the identification of causative agents can be difficult. Dust is thought to be a contributor to the pathological process, but well known carcinogens such as N-nitroso compounds have been detected in some environments. Further research on responsible agents is necessary and screening for detection of precursor gastric cancer lesions at the workplace merits consideration. PMID:12782770

Iris metastasis of gastric adenocarcinoma.

PubMed

Celebi, Ali Riza Cenk; Kilavuzoglu, Ayse Ebru; Altiparmak, U Emrah; Cosar, C Banu; Ozkiris, Abdullah

2016-03-08

Iris metastasis in patients with gastric cancer is extremely rare. Herein, it is aimed to report on a patient with gastric adenocarcinoma and iris metastasis. A 65-year-old patient with the history of gastric cancer was admitted for eye pain and eye redness on his left eye. There was ciliary injection, severe +4 cells with hypopyon in the anterior chamber and a solitary, friable, yellow-white, fleshy-creamy vascularized 2 mm × 4 mm mass on the upper nasal part of the iris within the left eye. The presented patient's mass lesion in the iris fulfilled the criteria of the metastatic iris lesion's appearance. The ocular metastasis occurred during chemotherapy. Iris metastasis can masquerade as iridocyclitis with pseudohypopyon or glaucoma. In patients with a history of gastric cancer that present with an iris mass, uveitis, and high intraocular pressure, ocular metastasis of gastric cancer should be a consideration.

Structural Diversity of Human Gastric Mucin Glycans*

PubMed Central

Jin, Chunsheng; Kenny, Diarmuid T.; Skoog, Emma C.; Padra, Médea; Adamczyk, Barbara; Vitizeva, Varvara; Thorell, Anders; Venkatakrishnan, Vignesh; Lindén, Sara K.; Karlsson, Niclas G.

2017-01-01

The mucin O-glycosylation of 10 individuals with and without gastric disease was examined in depth in order to generate a structural map of human gastric glycosylation. In the stomach, these mucins and their O-glycosylation protect the epithelial surface from the acidic gastric juice and provide the first point of interaction for pathogens such as Helicobacter pylori, reported to cause gastritis, gastric and duodenal ulcers and gastric cancer. The rational of the present study was to map the O-glycosylation that the pathogen may come in contact with. An enormous diversity in glycosylation was found, which varied both between individuals and within mucins from a single individual: mucin glycan chain length ranged from 2–13 residues, each individual carried 34–103 O-glycan structures and in total over 258 structures were identified. The majority of gastric O-glycans were neutral and fucosylated. Blood group I antigens, as well as terminal α1,4-GlcNAc-like and GalNAcβ1–4GlcNAc-like (LacdiNAc-like), were common modifications of human gastric O-glycans. Furthemore, each individual carried 1–14 glycan structures that were unique for that individual. The diversity and alterations in gastric O-glycosylation broaden our understanding of the human gastric O-glycome and its implications for gastric cancer research and emphasize that the high individual variation makes it difficult to identify gastric cancer specific structures. However, despite the low number of individuals, we could verify a higher level of sialylation and sulfation on gastric O-glycans from cancerous tissue than from healthy stomachs. PMID:28461410

Overview of Current Concepts in Gastric Intestinal Metaplasia and Gastric Cancer

PubMed Central

Adam, Jason D.; Borum, Marie L.; Koh, Joyce M.; Stephen, Sindu

2018-01-01

Gastric intestinal metaplasia is a precancerous change of the mucosa of the stomach with intestinal epithelium, and is associated with an increased risk of dysplasia and cancer. The pathogenesis to gastric cancer is proposed by the Correa hypothesis as the transition from normal gastric epithelium to invasive cancer via inflammation followed by intramucosal cancer and invasion. Multiple risk factors have been associated with the development of gastric intestinal metaplasia interplay, including Helicobacter pylori infection and associated genomics, host genetic factors, environmental milieu, rheumatologic disorders, diet, and intestinal microbiota. Globally, screening guidelines have been established in countries with high incidence. In the United States, no such guidelines have been developed due to lower, albeit increasing, incidence. The American Society for Gastrointestinal Endoscopy recommends a case-by-case patient assessment based upon epidemiology, genetics, and environmental risk factors. Studies have examined the use of a serologic biopsy to stratify risk based upon factors such as H pylori status and virulence factors, along with serologic markers of chronic inflammation including pepsinogen I, pepsinogen II, and gastrin. High-risk patients may then be advised to undergo endoscopic evaluation with mapping biopsies from the antrum (greater curvature, lesser curvature), incisura angularis, and corpus (greater curvature, lesser curvature). Surveillance guidelines have not been firmly established for patients with known gastric intestinal metaplasia, but include repeat endoscopy at intervals according to the histologic risk for malignant transformation. PMID:29606921

Subtotal gastrectomy for gastric cancer

PubMed Central

Santoro, Roberto; Ettorre, Giuseppe Maria; Santoro, Eugenio

2014-01-01

Although a steady decline in the incidence and mortality rates of gastric carcinoma has been observed in the last century worldwide, the absolute number of new cases/year is increasing because of the aging of the population. So far, surgical resection with curative intent has been the only treatment providing hope for cure; therefore, gastric cancer surgery has become a specialized field in digestive surgery. Gastrectomy with lymph node (LN) dissection for cancer patients remains a challenging procedure which requires skilled, well-trained surgeons who are very familiar with the fast-evolving oncological principles of gastric cancer surgery. As a matter of fact, the extent of gastric resection and LN dissection depends on the size of the disease and gastric cancer surgery has become a patient and “disease-tailored” surgery, ranging from endoscopic resection to laparoscopic assisted gastrectomy and conventional extended multivisceral resections. LN metastases are the most important prognostic factor in patients that undergo curative resection. LN dissection remains the most challenging part of the operation due to the location of LN stations around major retroperitoneal vessels and adjacent organs, which are not routinely included in the resected specimen and need to be preserved in order to avoid dangerous intra- and postoperative complications. Hence, the surgeon is the most important non-TMN prognostic factor in gastric cancer. Subtotal gastrectomy is the treatment of choice for middle and distal-third gastric cancer as it provides similar survival rates and better functional outcome compared to total gastrectomy, especially in early-stage disease with favorable prognosis. Nonetheless, the resection range for middle-third gastric cancer cases and the extent of LN dissection at early stages remains controversial. Due to the necessity of a more extended procedure at advanced stages and the trend for more conservative treatments in early gastric cancer, the

Gastric metastasis of cervix uteri carcinoma, rare cause of lower gastric stenosis.

PubMed

Moldovan, B; Banu, E; Pocreaţă, D; Buiga, R; Rogoz, S; Pripisi, L; Cimpeanu, L; Moldovan, A; Jeder, O; Badea, A; Biris, P

2012-01-01

the paper presents a rare case of metachronous gastric metastasis of uterine cervix cancer, clinically manifested through severe pyloric stenosis. 49-year-old patient, operated on in January 2009, with uterine cervix cancer (Squamous cell carcinoma T2bN1M0), is hospitalized in August 2011 with pyloric stenosis: epigastric pains, abundant, stasis, late postprandial emesis, significant weight loss, stomach form visible upon abdomen inspection. Endoscopy: antral stenosis with intact gastric mucosa, and CT-scan: circumferential intramural gastric tumor, stomach dilated in the upper part, lack of cleavage between the tumor and the liver bed of the gall bladder. CEA increased to 13,78 (below 5), CA 19-9 slightly increased 29.9 (below 27). The case is considered as a second neoplasia and a D2 subtotal gastrectomy was performed, with 1 positive ganglion out of 27 on block with atypical hepatectomy of segments 4-5 for liver invasion, the final mounting being Y Roux. The histopathological examination shows a gastric metastasis of squamous carcinoma, of uterine cervix origin, the invaded perigastric ganglion having the same aspect of uterine cervix carcinoma. The post-surgery evolution was favorable, under chemo radiotherapy the patient being alive without relapse at 9 months post-surgery. In the literature there are 2 more cases of gastric metastasis of uterine cervix carcinoma, and 4 of uterine carcinoma without topographic indication, but without the histological documentation of the tumor filiation, without data related to resecability or follow-up, the case at hand being, from this perspective, the first documented resectable metachronous gastric metastasis from a cervix uteri carcinoma. Celsius.

Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection

PubMed Central

Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

2015-01-01

AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. METHODS: A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. RESULTS: Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal

Gastric mucosa in Mongolian and Japanese patients with gastric cancer and Helicobacter pylori infection.

PubMed

Matsuhisa, Takeshi; Yamaoka, Yoshio; Uchida, Tomohisa; Duger, Davaadorj; Adiyasuren, Battulga; Khasag, Oyuntsetseg; Tegshee, Tserentogtokh; Tsogt-Ochir, Byambajav

2015-07-21

To investigate the characteristics of gastric cancer and gastric mucosa in a Mongolian population by comparison with a Japanese population. A total of 484 Mongolian patients with gastric cancer were enrolled to study gastric cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and 3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal complaints, no history of gastric operation or Helicobacter pylori eradication treatment, and no use of gastric secretion inhibitors such as histamine H2-receptor antagonists or proton pump inhibitors were enrolled. This study was conducted with the approval of the ethics committees of all hospitals. The triple-site biopsy method was used for the histologic diagnosis of gastritis and H. pylori infection in all Mongolian and Japanese cases. The infection rate of H. pylori and the status of gastric mucosa in H. pylori-infected patients were compared between Mongolian and Japanese subjects. Age (± 5 years), sex, and endoscopic diagnosis were matched between the two countries. Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of age, and approximately half of the cancers were located in the upper part of the stomach. Histologically, 65.7% of early cancers exhibited differentiated adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the prevalence was highest among young patients, and tended to decrease in patients aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia scores were significantly lower in Mongolian compared to Japanese H. pylori-positive patients (P < 0.0001), with the exception of the intestinal metaplasia score of

[Effect of manual acupuncture stimulation of "Zusanli" (ST 36) on gastric motility, and SP and motilin activities in gastric antrum and nucleus raphe magnus in gastric hyperactivity and hypoactivity rats].

PubMed

Yan, Chun-Chuan; Peng, Yan; Lin, Ya-Ping; Yi, Shou-Xiang; Chen, Ping; Hou, Yan-Ling; Shi, Dong-Mei

2013-10-01

To observe the changes of gastric motility and levels of substance P (SP) and motilin (MTL) in the gastric antrum and Nucleus Raphe Magnus (NRM) after manual acupuncture stimulation of "Zusanli" (ST 36) in gastric hyperactivity and hypoactivity rats, so as to analyze the role of NRM in acupuncture mediated adjustment of gastric motility. Fifty SD rats were randomly and equally divided into control, gastric hyperactivity (G-Hypera) model, gastric hypoactivity (G-Hypoa) model, acupuncture + G-Hypera and acupuncture + G-Hypoa groups (10 rats/group). G-Hypera model was established by intravenous (tail vein) injection of Maxolon (0.5 mL/200 g) and G-Hypoa model established by intravenous injection of Atropin (0.5 mL/200 g), respectively. After insertion of acupuncture needles into bilateral "Zusanli" (ST 36), the needles were repeatedly manipulated at a frequency of about 2 Hz for 5 min. The intragastric pressure was recorded and analyzed using a physiological signal analysis system. The SP and MTL contents of gastric antrum were measured by ELISA, and SP and MTL immunoactivity of NRM was determined by immunohistochemistry. In gastric hyperactivity rats, compared with the control group, the intragastric pressure (not systolic frequency), SP and MTL contents in the gastric antrum and MTL immunoactivity of NRM were significantly increased (P < 0.05, P < 0.01), while SP immunoactivity of NRM was apparently decreased in the G-Hypera model group (P < 0.01). After acupuncture stimulation, the intragastric pressure, gastric SP and MTL contents, and MTL immunoactivity of NRM were all significantly down-regulated (P < 0.05, P < 0.01), and SP immunoactivity of NRM was markedly up-regulated (P < 0.01) in comparison with the model group. In gastric hypoactivity rats, compared with the control group, the intragastric pressure and gastric systolic frequency, gastric SP and MTL contents, and MTL immunoactivity of NRM were significantly decreased (P < 0.05, PF < 0.01), while SP

Gastric Aspiration Models

PubMed Central

Davidson, Bruce A.; Alluri, Ravi

2016-01-01

The procedures described below are for producing gastric aspiration pneumonitis in mice with alterations for rats and rabbits described parenthetically. We use 4 different injury vehicles delivered intratracheally to investigate the inflammatory responses to gastric aspiration: Normal saline (NS) as the injury vehicle controlNS + HCl, pH = 1.25 (acid)NS + gastric particles, pH ≈ 5.3 (part.)NS + gastric particles + HCl, pH = 1.25 (acid + part.) The volume, pH, and gastric particle concentration all affect the resulting lung injury. In mice, we generally use an injury volume of 3.6 ml/kg (rat: 1.2 ml/kg, rabbit: 2.4 ml/kg), an injury pH (for the acid-containing vehicles) of 1.25, and a gastric particulate concentration (in the particulate-containing vehicles) of 10 mg/ml (rat: 40 mg/ml). In our hands this results in a maximal, non-lethal lung injury with ≤ 10% mortality for the most injurious vehicle (i.e., acid + part.) The maximum tolerable particulate concentration needs to be determined empirically for any new strains to be used, especially in genetically-altered mice, because an altered inflammatory response may have detrimental affects on mortality. We have extensive experience utilizing these procedures in the outbred strain, CD-1, as well as many genetically-altered inbred stains on the C57BL/6 background. Choice of strain should be carefully considered, especially in terms of strain-specific immune bias, to assure proper data interpretation. The size of the mouse should be ≥ 20 g at the time of injury. Smaller mice can be attempted, if necessary, but the surgical manipulation becomes increasingly more difficult and the surgery survival rate decreases substantially. There are no size or strain constraints for rat and rabbit models, but we generally use Long-Evans rats at 250–300 g and New Zealand White rats at ≈ 2 kg at the time of initial injury. PMID:27540561

Can the Long-Term Complications of Adjustable Gastric Banding Be Overcome? Preliminary Results of Adding Gastric Plication in Patients with Impending Gastric Band Failure.

PubMed

Kim, Su Bin; Kim, Seong Min

2015-09-01

A small percentage of patients fitted with a gastric band still experience "failure." Here, the authors demonstrate the safety and feasibility of band preserving-laparoscopic gastric plication (BP-LGP), which was designed to improve weight loss and decrease gastric band adjustment frequency and thereby improve patient quality of life. All 6 patients involved in this study had a gastric band in place for more than 1 year; the median interval from gastric banding to BP-LGP was 31.7 months (range, 19.7-49.9 months). Five (83.3%) patients were female. Preoperative median body mass index (BMI) at gastric banding was 35.4 kg/m(2) (range, 31.9-43.9 kg/m(2)), median nadir BMI with the gastric band was 25.7 kg/m(2) (range, 20.9-31.0 kg/m(2)), and percentage excess BMI loss (%EBMIL) ranged from 24.3% to 123.6%. Indications for BP-LGP were as follows: chronic gastric prolapse in 2 patients (33.3%), pouch-esophageal dilatation in 3 (50.0%), and insufficient weight loss in 4 (66.6%), which included 2 patients with weight loss failure (%EBMIL of <30%). The 6 patients consecutively underwent surgery from May 2014 to January 2015. No conversion to open surgery was necessary, and no perioperative complication or mortality occurred. Mean operative time was 190 minutes. All patients showed weight loss after revision and showed resolution of troublesome signs and symptoms. Median follow-up after revision was 7.3 months (range, 5.7-10.1 months), median BMI at last follow-up was 27.6 kg/m(2) (range, 22.7-34.0 kg/m(2)), and median %EBMIL was 75.7% (range, 21.0%-103.6%). Median fill volume before revision was 6.1 mL (range, 2.7-11.0 mL), and median fill volume after revision was 0.3 mL (range, 0.0-5.3 mL). Three patients (50%) had an empty band at last follow-up. This novel method of bariatric revision (modified BP-LGP) might have a role as a salvage procedure in patients with impending gastric band failure.

A comparison of Helicobacter pylori and non-Helicobacter pylori Helicobacter spp. Binding to canine gastric mucosa with defined gastric glycophenotype.

PubMed

Amorim, Irina; Freitas, Daniela P; Magalhães, Ana; Faria, Fátima; Lopes, Célia; Faustino, Augusto M; Smet, Annemieke; Haesebrouck, Freddy; Reis, Celso A; Gärtner, Fátima

2014-08-01

The gastric mucosa of dogs is often colonized by non-Helicobacter pylori helicobacters (NHPH), while H. pylori is the predominant gastric Helicobacter species in humans. The colonization of the human gastric mucosa by H. pylori is highly dependent on the recognition of host glycan receptors. Our goal was to define the canine gastric mucosa glycophenotype and to evaluate the capacity of different gastric Helicobacter species to adhere to the canine gastric mucosa. The glycosylation profile in body and antral compartments of the canine gastric mucosa, with focus on the expression of histo-blood group antigens was evaluated. The in vitro binding capacity of FITC-labeled H. pylori and NHPH to the canine gastric mucosa was assessed in cases representative of the canine glycosylation pattern. The canine gastric mucosa lacks expression of type 1 Lewis antigens and presents a broad expression of type 2 structures and A antigen, both in the surface and glandular epithelium. Regarding the canine antral mucosa, H. heilmannii s.s. presented the highest adhesion score whereas in the body region the SabA-positive H. pylori strain was the strain that adhered more. The canine gastric mucosa showed a glycosylation profile different from the human gastric mucosa suggesting that alternative glycan receptors may be involved in Helicobacter spp. binding. Helicobacter pylori and NHPH strains differ in their ability to adhere to canine gastric mucosa. Among the NHPH, H. heilmannii s.s. presented the highest adhesion capacity in agreement with its reported colonization of the canine stomach. © 2014 John Wiley & Sons Ltd.

Noninvasive evaluation of gastric emptying and gastric wall thickness in SLE patients.

PubMed

Shen, Hao-Lin; Yang, Shu-Ping; Wang, Kang-Jian; Huang, Bei-Lei; Huang, Wen-Bao; Wu, Jin-Zhi; Lyu, Guo-Rong

2017-04-01

The objective of this study is to evaluate the gastric emptying in patients with systemic lupus erythematosus (SLE) with gastrointestinal involvement using three-dimensional (3D) ultrasonography. The gastric emptying times at 25% (T1), 50% (T2), and 75% (T3) of SLE patients with gastrointestinal involvement (n = 40) and healthy controls (n = 80) were evaluated and compared. In addition, the correlations among the gastric wall thickness, SLE disease activity index (SLEDAI), and upper gastrointestinal symptoms were calculated. The gastric wall thickness was correlated with the SLEDAI (r = 0.928, p < 0.001) and the upper gastrointestinal symptom index (r = 0.848, p < 0.001). The emptying times T1, T2, and T3 of the SLE patients were 17.08 ± 2.65 min (mean ± standard deviation), 39.85 ± 6.54 min, and 83.58 ± 7.12 min, respectively. For healthy controls, they were 19.65 ± 5.39 min, 41.08 ± 7.51 min, and 70.34 ± 8.03 min. The T1 of the SLE patients was shorter (p < 0.01), while the T3 was longer (p < 0.001). Moreover, T3 in the SLE group had the best correlation with the upper gastrointestinal symptom index (r = 0.553, p < 0.001). T1 in the SLE group was anti-correlated with early satiety (r = -0.366, p < 0.05). Combining the emptying times T1 and T3, as well as the gastric wall thickness, the SLEDAI and the upper gastrointestinal symptoms index can provide accurate clinical diagnosis of SLE with gastric involvement.

A common molecular signature of intestinal-type gastric carcinoma indicates processes related to gastric carcinogenesis.

PubMed

Binato, Renata; Santos, Everton Cruz; Boroni, Mariana; Demachki, Samia; Assumpção, Paulo; Abdelhay, Eliana

2018-01-26

Gastric carcinoma (GC) is one of the most aggressive cancers and the second leading cause of cancer death in the world. According to the Lauren classification, this adenocarcinoma is divided into two subtypes, intestinal and diffuse, which differ in their clinical, epidemiological and molecular features. Several studies have attempted to delineate the molecular signature of gastric cancer to develop new and non-invasive screening tests that improve diagnosis and lead to new treatment strategies. However, a consensus signature has not yet been identified for each condition. Thus, this work aimed to analyze the gene expression profile of Brazilian intestinal-type GC tissues using microarrays and compare the results to those of non-tumor tissue samples. Moreover, we compared our intestinal-type gastric carcinoma profile with those obtained from populations worldwide to assess their similarity. The results identified a molecular signature for intestinal-type GC and revealed that 38 genes differentially expressed in Brazilian intestinal-type gastric carcinoma samples can successfully distinguish gastric tumors from non-tumor tissue in the global population. These differentially expressed genes participate in biological processes important to cell homeostasis. Furthermore, Kaplan-Meier analysis suggested that 7 of these genes could individually be able to predict overall survival in intestinal-type gastric cancer patients.

Vomiting and gastric electrical dysrhythmia in dogs.

PubMed

Ueno, T; Chen, J D Z

2004-04-01

The correlation between gastric myoelectrical activity (GMA) and gastrointestinal symptoms such as nausea and vomiting is poorly understood. The aim of this study was to assess the association of GMA with vomiting induced by retrograde gastric electrical stimulation or duodenal balloon distention. Ten dogs were involved in this study. Vomiting was induced by retrograde gastric electrical stimulation in 6 dogs and by duodenal balloon distention in 4 dogs. Computerized spectral analysis and visual analysis were applied to detect the GMA change during various periods before and after vomiting. Gastric dysrhythmia preceded vomiting but was of brief duration. The major pattern of dysrhythmia immediately before vomiting was tachyarrhythmia and gastric slow wave was completely uncoupled before vomiting. Gastric dysrhythmia and slow wave uncoupling were also noticed immediately after vomiting but the dogs recovered quickly. The major pattern of dysrhythmia after vomiting was arrhythmia. GMA was normal during the periods other than 5 min before and during vomiting and 5 min after vomiting. Gastric dysrhythmia seems to be the cause of vomiting induced by retrograde gastric electrical stimulation or duodenal balloon distention. It is brief and characterized with tachyarrhythmia and uncoupling.

[Differential diagnosis of ulcerated gastric lesions].

PubMed

Llorens, P; Atlschiller, H; Pisano, R; Moya, P

1986-01-01

The semiological characteristics of the ulcerated gastric lesions, benign and malignant, are on study. Its frequency and location is analysed in 32,829 subjects of 40 or more years of age, apparently in good health, finding gastric ulcers in 2.98% been unique in 2.3% and multiple in 0.68%. A symptomatic group of 8,765 people of 40 or more years, showed gastric ulcer in 7.11% been unique in 5.18% and multiple in 1.93%. It is also reported the frequency of gastric cancer in both studied groups, which leads to permanently propose the differential diagnostic with benign lesions, underlying by its frequency those of ulcerated type. The value of the gastric biopsy in differential diagnosis represents finally an aid of major importance because its high yield.

Gastric neuroendocrine tumours.

PubMed

Crosby, David A; Donohoe, Claire L; Fitzgerald, Louise; Muldoon, Cian; Hayes, Brian; O'Toole, Dermot; Reynolds, John V

2012-01-01

Gastric neuroendocrine tumours (NETs) are increasingly recognised, and management decisions may be difficult due to an incomplete understanding of aetiology, natural history and optimum therapy. This article presents a current understanding based on recent advances in epidemiology, classification, molecular profiling, and treatment. Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Gastric NETs may be divided into three clinical prognostic groups: type I is associated with autoimmune atrophic gastritis and hypergastrinaemia, type II is associated with Zollinger-Ellison syndrome, and type III lesions are gastrin-independent, have the greatest metastatic potential and poorest prognosis. There has been an increased frequency of gastric NETs reported. Management approaches have evolved in parallel with advances in endoscopic staging and surgery, as well as improved understanding of the biology and natural history of NETs. Gastric NETs present a spectrum of activity from indolent tumours to metastatic malignancy. Treatment decisions for patients must be individualised and are best managed by a multidisciplinary team approach. The current evidence base is limited to small series and efforts to treat patients within clinical networks of expertise are warranted. Copyright © 2012 S. Karger AG, Basel.

Gastric ulceration in an equine neonate

PubMed Central

Lewis, Susan

2003-01-01

A 24-hour-old colt presented with clinical signs consistent with gastric ulceration. Treatment was initiated with a histamine type-2 receptor antagonist and clinical signs resolved. Gastroscopy at 16 d confirmed the presence of a gastric ulcer. Although gastric ulceration is common in foals, it is rarely reported in foals this young. PMID:12757136

Epstein-Barr Virus in Gastric Carcinoma

PubMed Central

Nishikawa, Jun; Yoshiyama, Hironori; Iizasa, Hisashi; Kanehiro, Yuichi; Nakamura, Munetaka; Nishimura, Junichi; Saito, Mari; Okamoto, Takeshi; Sakai, Kouhei; Suehiro, Yutaka; Yamasaki, Takahiro; Oga, Atsunori; Yanai, Hideo; Sakaida, Isao

2014-01-01

The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor the clonal EBV genome. Gastric carcinoma associated with EBV has distinct clinicopathological features, occurs predominately in men and in younger-aged individuals, and presents a generally diffuse histological type. Most cases of EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte infiltration. The immunological reactiveness in the host may represent a relatively preferable prognosis in EBV-positive cases. This fact highlights the important role of EBV in the development of EBV-associated gastric carcinoma. We have clearly proved direct infection of human gastric epithelialcells by EBV. The infection was achieved by using a recombinant EBV. Promotion of growth by EBV infection was observed in the cells. Considerable data suggest that EBV may directly contribute to the development of EBV-associated GC. This tumor-promoting effect seems to involve multiple mechanisms, because EBV affects several host proteins and pathways that normally promote apoptosis and regulate cell proliferation. PMID:25386788

Gastric epithelioid haemangioendothelioma.

PubMed

Tavares, A B; Almeida, A G; Viveiros, F A; Cidade, C N; Barbosa, J M

2011-05-10

Epithelioid haemangioendothelioma (EHE) is a rare tumour of vascular origin, characterised by celular proliferation, endotelial, epitelioid or hystiocitoid. It may develop in any organ, but it is more common in lung and liver. Surgery is the recommended treatment; however, in case of a potentially benign situation, an expectant attitude should be adopted. The case reports a 71-year-old female who underwent a laparotomy for a colonic adenocarcinoma. During surgery, a polypoid lesion in the dependency of the gastric wall was found incidentally, which was removed. Histopathology and immunohistochemical analysis confirmed the diagnosis of EHE. Gastric vascular neoplasms represent about 0.9-3.3% of all gastric tumours. Usually have a good prognosis, but due to the borderline biological behaviour of these tumours, it is important to have a detailed clinical evaluation at follow-up of these patients.

[Gastric emptying in the aged. Effect of clebopride].

PubMed

Schraier, M; Guinsburg, R; Valguarnera, J; Rosenfeld, L

1984-01-01

Fifteen patients considered as "geronts" (average 70 years) have been performed Radiology, Endoscopy and Gastric Biopsies, with differents degrees of chronic gastritis as only gastric pathology, and 8 "healthy adults" (controls) were assessed on the T1/2 of gastric evacuation, with a solid meal marked with DPTA Tc 99 and measurement of isotopic activity in Gamma Camera before and after administration of a therapeutic dose of Clebopride. In the basal trial it was found that geronts gastric emptying is delayed more than controls (112 and 89 minutes). The activity of Clebopride revealed a significant decrease in both groups, being more important in geronts. This findings suggests the clinic usefulness in different pathological situations, where its useful to accelerate the time of gastric evacuation (gastric esofagic reflux, gastric ulcer) and in the geront with dispeptic symptoms and chronic gastritis related to age, as the only gastric pathology.

Gene methylation in gastric cancer.

PubMed

Qu, Yiping; Dang, Siwen; Hou, Peng

2013-09-23

Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Gastric heterotopia in the rectum. A rare cause of ectopic gastric tissue.

PubMed

Salem, George A; Fazili, Javid; Ali, Tauseef

2017-03-01

Gastric heterotopia refers to the discovery of normal gastric tissue at foreign, unexpected sites. It has been described anywhere in the alimentary tract, even in the mediastinum, scrotum, and spinal cord. It is not uncommonly seen in the oesophagus or small intestine. However, large bowel lesions are rare, with the most common location of colonic lesions is the rectum. Although it is a rare entity, it may be the source for significant problems such as rectal bleeding, abdominal pain, deep rectal pain, and malignancy. Here, we report an additional case of gastric heterotopia in the rectum of a 56year old gentleman, and review the literature. Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Gastric tumor from metastasis of breast cancer.

PubMed

Yamamoto, D; Yoshida, H; Sumida, K; Ueyama, Y; Kanematsu, S; Shoji, T; Sueoka, N; Tanaka, K; Tsubota, Y; Kon, M

2010-09-01

Metastatic tumours of the stomach have been reported to result from various types of cancer. Among them, gastric metastasis from breast cancer has been recognised in 0.3-18% patients (1-4). Here, a rare case of metastatic gastric tumour derived from breast carcinoma is reported. Gastric endoscopy confirmed a large, friable mass (approximately 5 cm in diameter) in the upper part of the gastric body. The mass within the stomach was difficult to distinguish from primary gastric cancer, although biopsies of this lesion revealed the characteristics of adenocarcinoma. In addition, immunohistochemistry showed the positive expression of mammaglobin. Taken together, the evidence pointed to metastasis of breast cancer to the stomach. The patient was treated with hormonal therapy (letrozole), and the size of the metastasis in the stomach was markedly reduced. Therefore, a gastric metastasis from breast cancer was diagnosed successfully using immunohistochemistry and unnecessary surgery was avoided. In conclusion, although gastric metastatic tumours derived from breast carcinoma are rare, their accurate pre-operative diagnosis and appropriate systemic treatment is essential.

General Information about Gastric Cancer

MedlinePlus

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

Gastric emptying abnormal in duodenal ulcer

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

Holt, S.; Heading, R.C.; Taylor, T.V.

1986-07-01

To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison ofmore » emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease.« less

Gastric Lgr5+ stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice

PubMed Central

Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

2016-01-01

The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5+ stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5+ stem cells by the inducible Cre-LoxP system and marked mutant Lgr5+ stem cells and their progeny with Cre-reporter Rosa26tdTomato. Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5+ stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5+ chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5+ cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5+ stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression. PMID:27091432

Gastric Lgr5(+) stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice.

PubMed

Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

2016-07-01

The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5(+) stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5(+) stem cells by the inducible Cre-LoxP system and marked mutant Lgr5(+) stem cells and their progeny with Cre-reporter Rosa26(tdTomato). Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5(+) stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5(+) chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5(+) cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5(+) stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression.

Premalignant gastric lesions in patients with gastric mucosa-associated lymphoid tissue lymphoma and metachronous gastric adenocarcinoma: a case-control study.

PubMed

Capelle, Lisette G; den Hoed, Caroline M; de Vries, Annemarie C; Biermann, Katharina; Casparie, Mariel K; Meijer, Gerrit A; Kuipers, Ernst J

2012-01-01

Patients with gastric mucosa-associated lymphoid tissue lymphoma or diffuse large B-cell lymphoma have an increased risk of developing gastric carcinoma (GC). Identifying patients at high GC risk may lead to improved survival and prognosis. The aim of this case-control study was to evaluate whether premalignant gastric lesions are more prevalent and severe in gastric lymphoma (GL) patients with a subsequent diagnosis of GC than in those without GC. Patients with a first GL diagnosis from 1991-2008 were identified in the Dutch histopathology registry (PALGA). Cases were patients with a diagnosis of GL and a subsequent diagnosis of GC. Controls were patients with a diagnosis of GL without GC development. In total, eight cases (mean follow-up 5.5 years) and 31 controls (mean follow-up 5.3 years) were included (mean age 60 years). At lymphoma diagnosis, six (75%) cases were diagnosed with premalignant lesions, whereas in the control group, 21 (68%) had histological evidence for premalignant lesions (P=0.69). At GC diagnosis, five (63%) cases showed intestinal metaplasia in the surrounding gastric mucosa. In 22 (71%) controls premalignant lesions were present at the end of follow-up (P=0.47). No differences were demonstrated in the prevalence of premalignant lesions of cases and controls at GL diagnosis or the end of follow-up. As the prevalence of premalignant lesions is substantial in both the groups of patients, careful endoscopic surveillance of GL patients is warranted not only for recurrence of lymphoma, but also for progression to adenocarcinoma.

Glucose metabolism in gastric cancer: The cutting-edge

PubMed Central

Yuan, Lian-Wen; Yamashita, Hiroharu; Seto, Yasuyuki

2016-01-01

Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer. PMID:26877609

[Laparoscopic gastric sleeve in gastric volvulus secondary to diaphragmatic eventration in an adult patient].

PubMed

Gálvez-Valdovinos, Ramiro; Marín-Santillán, Ernesto; Funes-Rodríguez, Juan Francisco; López-Ambriz, Gustavo

2016-01-01

Acute gastric volvulus is a rare, but potentially life-threatening, cause of upper gastrointestinal obstruction. Male of 60 years old with severe epigastric pain and abdominal distension with haematemesis on two occasions. The patient was haemodynamically stable, with abdominal distension and palpable epigastric fullness. Hematic cytology showed: haemoglobin 8.2g/dl and haematocrit 27%. Abdominal X-ray showed an elevation of left diaphragm with a hugely dilated stomach. A nasogastric tube was inserted. Endoscopy was performed. There was no active bleeding, but it was impossible to reach the duodenum due to the stomach distortion. The upper gastrointestinal X-ray study showed the appearance of an inverted stomach in the chest and an organoaxial gastric torsion. The CT scans of thorax and abdomen showed a gastric ascent into the thoracic cavity. Laparoscopic surgery was performed, finding the left hemi-diaphragm elevated, and the stomach, splenic angle of the colon, the spleen and tail of the pancreas were also raised. A linear gastrectomy (gastric sleeve) was performed. The postoperative progress was satisfactory. Oral feeding was started 72 hours after surgery, and the patient was discharged, and has remained asymptomatic during the following by 8 years. Emergency physicians must maintain a high level of suspicion in patients that present with signs and symptoms suggesting upper digestive tract occlusion. The gastric sleeve is an excellent alternative to avoid recurrence of gastric volvulus. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Human gastric cancer modelling using organoids.

PubMed

Seidlitz, Therese; Merker, Sebastian R; Rothe, Alexander; Zakrzewski, Falk; von Neubeck, Cläre; Grützmann, Konrad; Sommer, Ulrich; Schweitzer, Christine; Schölch, Sebastian; Uhlemann, Heike; Gaebler, Anne-Marlene; Werner, Kristin; Krause, Mechthild; Baretton, Gustavo B; Welsch, Thilo; Koo, Bon-Kyoung; Aust, Daniela E; Klink, Barbara; Weitz, Jürgen; Stange, Daniel E

2018-04-27

Gastric cancer is the second leading cause of cancer-related deaths and the fifth most common malignancy worldwide. In this study, human and mouse gastric cancer organoids were generated to model the disease and perform drug testing to delineate treatment strategies. Human gastric cancer organoid cultures were established, samples classified according to their molecular profile and their response to conventional chemotherapeutics tested. Targeted treatment was performed according to specific druggable mutations. Mouse gastric cancer organoid cultures were generated carrying molecular subtype-specific alterations. Twenty human gastric cancer organoid cultures were established and four selected for a comprehensive in-depth analysis. Organoids demonstrated divergent growth characteristics and morphologies. Immunohistochemistry showed similar characteristics to the corresponding primary tissue. A divergent response to 5-fluoruracil, oxaliplatin, irinotecan, epirubicin and docetaxel treatment was observed. Whole genome sequencing revealed a mutational spectrum that corresponded to the previously identified microsatellite instable, genomic stable and chromosomal instable subtypes of gastric cancer. The mutational landscape allowed targeted therapy with trastuzumab for ERBB2 alterations and palbociclib for CDKN2A loss. Mouse cancer organoids carrying Kras and Tp53 or Apc and Cdh1 mutations were characterised and serve as model system to study the signalling of induced pathways. We generated human and mouse gastric cancer organoids modelling typical characteristics and altered pathways of human gastric cancer. Successful interference with activated pathways demonstrates their potential usefulness as living biomarkers for therapy response testing. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Anti-gastric ulcer effect of Kaempferia parviflora.

PubMed

Rujjanawate, C; Kanjanapothi, D; Amornlerdpison, D; Pojanagaroon, S

2005-10-31

Kaempferia parviflora is a Zingiberaceous plant, which has been reputed for its beneficial medicinal effects. The present study was undertaken to evaluate the Kaempferia parviflora ethanolic extract (KPE) for its anti-gastric ulcer activity by experimental models. Oral administration of the KPE at 30, 60 and 120 mg/kg significantly inhibited gastric ulcer formation induced by indomethacin, HCl/EtOH and water immersion restraint-stress in rats. In pylorus-ligated rats, pretreatment with the KPE had no effect on gastric volume, pH and acidity output. In ethanol-induced ulcerated rats, gastric wall mucus was significantly preserved by the KPE pretreatment at doses of 60 and 120 but not at 30 mg/kg. The findings indicate that the ethanolic extract of Kaempferia parviflora possesses gastroprotective potential which is related partly to preservation of gastric mucus secretion and unrelated to the inhibition of gastric acid secretion.

Inactivation of Smad4 in gastric carcinomas.

PubMed

Powell, S M; Harper, J C; Hamilton, S R; Robinson, C R; Cummings, O W

1997-10-01

Allelic loss of chromosome 18q has been noted in intestinal type gastric adenocarcinomas. Smad4 is a gene located at 18q that was recently cloned in humans and found to be significantly altered in pancreatic cancers. We sought to determine whether Smad4 genetic alterations played a significant role in gastric tumorigenesis by studying 35 gastric adenocarcinomas of all histopathological types and pathological stages. Microdissected specimens were used for mutational analysis of Smad4 at the nucleotide level, including the entire coding region and intron/exon boundaries. Allelic imbalance was also analyzed at the Smad4 locus using two nearby microsatellite markers. One case of apparent biallelic inactivation of Smad4 was found in our study of 35 gastric carcinomas. A nonsense point mutation at codon 334 was demonstrated, which, similar to other Smad4 mutations, is predicted to truncate the conserved COOH-terminal domain of this protein. This Smad4 C to T transition mutation was proven to be somatically acquired. Allelic loss was also noted on chromosome 18q at a marker near Smad4 in this mutated gastric cancer, apparently producing complete inactivation of Smad4 in this tumor. Significant 18q allelic loss (56% of 34 informative cases) was noted in our gastric carcinomas using microsatellite markers near the Smad4 locus, regardless of histological subtype or pathological stage. Additionally, three cases of microsatellite instability were observed. Thus, Smad4 inactivation was noted in our gastric carcinomas; however, this event was rare. The frequent loss of chromosomal arm 18q observed in gastric cancers suggests the presence of other tumor suppressor genes in this region that are involved in gastric tumorigenesis. Further studies are needed to identify these other targets of inactivation during gastric cancer development.

Gastric biomarkers: a global review.

PubMed

Baniak, Nick; Senger, Jenna-Lynn; Ahmed, Shahid; Kanthan, S C; Kanthan, Rani

2016-08-11

Gastric cancer is an aggressive disease with a poor 5-year survival and large global burden of disease. The disease is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Despite the many prognostic, predictive, and therapeutic biomarkers investigated to date, gastric cancer continues to be detected at an advanced stage with resultant poor clinical outcomes. This is a global review of gastric biomarkers with an emphasis on HER2, E-cadherin, fibroblast growth factor receptor, mammalian target of rapamycin, and hepatocyte growth factor receptor as well as sections on microRNAs, long noncoding RNAs, matrix metalloproteinases, PD-L1, TP53, and microsatellite instability. A deeper understanding of the pathogenesis and biological features of gastric cancer, including the identification and characterization of diagnostic, prognostic, predictive, and therapeutic biomarkers, hopefully will provide improved clinical outcomes.

Blunt gastric injuries.

PubMed

Oncel, Didem; Malinoski, Darren; Brown, Carlos; Demetriades, Demetrios; Salim, Ali

2007-09-01

Gastric rupture after blunt abdominal trauma is a rare injury with few reports in the literature. The purpose of this study was to review our experience with blunt gastric injuries and compare outcomes with small bowel or colon injuries. All patients with hollow viscus perforations after blunt abdominal trauma from 1992 to 2005 at our level I trauma center were reviewed. Of 35,033 blunt trauma admissions, there were 268 (0.7%) patients with a total of 319 perforating hollow viscus injuries, 25 (0.07%) of which were blunt gastric injuries. When compared with the small bowel or colon injuries, the blunt gastric injury group had a higher Injury Severity Score (22 versus 17, P = 0.04), more patients with a chest Abbreviated Injury Score greater than 2 (36% versus 12%, P < 0.01), and a shorter interval from injury to laparotomy (221 versus 366 minutes, P = 0.017). Multivariate analysis identified five independent risk factors for mortality: age older than 55 years, head Abbreviated Injury Score greater than 2, chest Abbreviated Injury Score greater than 2, the presence of hypotension on admission, and Glasgow Coma Scale 8 or less. The results of this study suggest that mortality in patients with blunt hollow viscus injuries can be attributed to concurrent head and chest injuries, but not the specific hollow viscus organ that is injured.

Gastric bypass reduces fat intake and preference

PubMed Central

Bueter, Marco; Theis, Nadine; Werling, Malin; Ashrafian, Hutan; Löwenstein, Christian; Athanasiou, Thanos; Bloom, Stephen R.; Spector, Alan C.; Olbers, Torsten; Lutz, Thomas A.

2011-01-01

Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation. PMID:21734019

Gastric bypass reduces fat intake and preference.

PubMed

le Roux, Carel W; Bueter, Marco; Theis, Nadine; Werling, Malin; Ashrafian, Hutan; Löwenstein, Christian; Athanasiou, Thanos; Bloom, Stephen R; Spector, Alan C; Olbers, Torsten; Lutz, Thomas A

2011-10-01

Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation.

Gastric gallium-67 uptake in gastritis

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

Yeh, E.L.; Tisdale, P.L.; Zielonka, J.S.

1983-12-01

Even though Ga-67 imaging has been used widely in the diagnosis of malignant as well as inflammatory lesions, its uptake in the stomach has been reported in the literature mainly in gastric lymphoma and carcinoma. As shown in this case, intense gastric uptake of the radionuclide may be seen in common gastritis without malignancy. Perhaps the benign gastric uptake of Ga-67 deserves more emphasis.

Pathobiology of Helicobacter pylori-induced Gastric Cancer

PubMed Central

Amieva, Manuel; Peek, Richard M.

2015-01-01

Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth.

PubMed

Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

2016-01-01

Bruton's tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer.

Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

PubMed Central

Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

2016-01-01

Bruton’s tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer. PMID:27508020

The impact of gastric distension on the lower esophageal sphincter and its exposure to acid gastric juice.

PubMed

Ayazi, Shahin; Tamhankar, Anand; DeMeester, Steven R; Zehetner, Joerg; Wu, Calvin; Lipham, John C; Hagen, Jeffrey A; DeMeester, Tom R

2010-07-01

The lower esophageal sphincter (LES) in patients with gastroesophageal reflux disease often has a low resting pressure and a short abdominal length. The mechanism by which this occurs is unknown. We hypothesize that gastric distension causes progressive effacement of the abdominal portion of the LES, exposing it to acid injury resulting in mucosal and sphincter damage. Our aim was to assess in normal subjects the effect of gastric distension on the LES length and pressure and its exposure to acid gastric juice. Eleven asymptomatic volunteers had their LES length and pressure measured before and during gastric distension. The location of the pH step-up point (shift from gastric pH to a pH >4) was also measured before and after distension. Progressive gastric distension with air resulted in progressive shortening of LES (R = 0.89, P < 0.0001). After infusion of 750 cc of air there was a significant reduction in the median LES length from 4 to 2.6 cm (P = 0.001). This change occurred in the abdominal length of the LES (2.6-1.4 cm [P = 0.001]) and not in the thoracic length. At rest the pH step-up point was 0.5 cm above the lower border of the LES and with distension moved a median of 1 cm cephalad within the LES. Simultaneously with the loss of length there was a reduction in LES pressure (27.4-23.4 mm Hg, P = 0.02). Gastric distension causes progressive shortening of the abdominal length of the LES and a reduction in its pressure. The process exposes the effaced mucosa and sphincter to acid gastric juice.

Should peri-gastrectomy gastric acidity be our focus among gastric cancer patients?

PubMed

Huang, Lei; Xu, A-Man; Li, Tuan-Jie; Han, Wen-Xiu; Xu, Jing

2014-06-14

To investigate the necessity and correctness of acid suppression pre- and post-gastrectomy among gastric carcinoma (GC) patients. From June 2011 to April 2013, 99 patients who were diagnosed with GC or adenocarcinoma of the gastroesophageal junction (type II or III) and needed surgical management were enrolled. They all underwent gastrectomy by the same operators [35 undergoing total gastrectomy (TG) plus Roux-en-Y reconstruction, 34 distal gastrectomy (DG) plus Billroth I reconstruction, and 30 proximal gastrectomy (PG) plus gastroesophagostomy]. We collected and analyzed their gastrointestinal juice and tissues from the pre-operational day to the 5(th) day post-operation, and 6 mo post-surgery. Gastric pH was detected with a precise acidity meter. Gastric juice contents including potassium, sodium and bicarbonate ions, urea nitrogen, direct and indirect bilirubin, and bile acid were detected using Automatic Biochemical Analyzer. Data regarding tumor size, histological type, tumor penetration and tumor-node-metastasis (TNM) stage were obtained from the pathological records. Reflux symptoms pre- and 6 mo post-gastrectomy were evaluated by reflux disease questionnaire (RDQ) and gastroesophageal reflux disease questionnaire (GERD-Q). SPSS 16.0 was applied to analyze the data. Before surgery, gastric pH was higher than the threshold of hypoacidity (4.25 ± 1.45 vs 3.5, P = 0.000), and significantly affected by age, tumor size and differentiation grade, and potassium and bicarbonate ions; advanced malignancies were accompanied with higher pH compared with early ones (4.49 ± 1.31 vs 3.66 ± 1.61, P = 0.008). After operation, gastric pH in all groups was of weak-acidity and significantly higher than that pre-gastrectomy; on days 3-5, comparisons of gastric pH were similar between the 3 groups. Six months later, gastric pH was comparable to that on days 3-5; older patients were accompanied with higher total bilirubin level, indicating more serious reflux (r = 0.238, P

Surgical Elimination of the Gastric Digestion by Roux-en-Y Gastric Bypass Impacts on Food Sensitisation-a Pilot Study.

PubMed

Shakeri-Leidenmühler, Soheila; Lukschal, Anna; Schultz, Cornelia; Bohdjalian, Arthur; Langer, Felix; Birsan, Tudor; Diesner, Susanne C; Greisenegger, Elli K; Scheiner, Otto; Kopp, Tamara; Jensen-Jarolim, Erika; Prager, Gerhard; Untersmayr, Eva

2015-12-01

Impairment of gastric digestion due to pH elevation increases the risk for food allergy induction. As patients after Roux-en-Y gastric bypass (RYGB) surgery have lower gastric acidity and less gastric gland secretion, we aimed to analyse in a prospective study the effect of limiting gastric digestion capacity by surgical intervention on the immune response towards allergens. Nine patients undergoing RYGB surgery for morbid obesity and one control patient having undergone surgery for treatment of an incisional hernia were enrolled in the study. Before and 1, 3, 6, 9 and 12 months after surgery, blood was collected for analysis of specific IgE antibodies, and patients were subjected to skin prick testing with 16 food and 18 aeroallergens. Skin prick test results revealed an increase of positive reactions indicating sensitisations towards the tested food and aeroallergens in 77.8 and 88.9 % of the patients, respectively, after surgical elimination of gastric digestion. These results were in line with elevated titers of food- and aeroallergen-specific IgE antibodies in 7 out of 9 (7/9) and 5/9 patients, respectively, after RYGB surgery. Serum cytokine levels revealed a mixed response for IFN-γ and were mostly beneath detection limit for IL-4. A change of IgE reactivity pattern occurred after impairment of gastric digestion due to surgical elimination underlining the important gastric gatekeeping function during oral sensitisation. Even though this study indicates an increased allergy risk for gastric bypass patients, further studies are needed to investigate in-depth the immunological changes associated with RYGB surgery.

[Gastritis associated with duodeno-gastric reflux].

PubMed

Diarra, M; Konate, A; Traore, C B; Drabo, M; Soukho, A espouse Diarra; Kalle, A; Dembele, M; Traore, H A; Maiga, M Y

2007-01-01

Our main objective was to study gastritis associated to duodeno-gastric reflux. It is about a longitudinal study case/witness, paired according to the sex and the age. It was unrolled from February 2005 to January 2006 in the digestive diseases department of the hospital Gabriél Touré, and endoscopic centers of Promenade des Angevins, and clinique Farako. The patients profited from an upper digestive endoscopy to appreciate endoscopic aspect of gastritis associated to bile in the stomach mucus lake. The gastric biopsies were systematic. This study included 50 patients having gastritis associated to bile in gastric mucus lake compared to 50 patients having gastritis associated to clearly gastric mucus lake. The sex-ratio was 1.26 in favour of men. The average age of the patients was of 41.30 +/- 15.43 years. On the symptomatic hand, fetid breath was significantly met in duodeno-gastric reflux (p = 0.013). Potash consumption in the "tô" (millet cake) was significantly reported in gastritis associated to bile in gastric mucus lake (p = 0.042). The endoscopic aspects were comparable. Histological aspects of nonatrophic chronic gastritis were significantly mint in witnesses as well into the antrum as into the fundus (p = 0.0001 and p = 0.00023). The reactional gastritis aspect was the prerogative of duodenogastric reflux (p ranging between 10(-6) and 3.10 (-6). Helicobacter pylori infection was found comparable in the two groups (p = 0.297). Dysplasia although rare was found only in gastritis associated to duodeno-gastric reflux. Gastritis associated to bile in gastric mucus does not se,nm to have specific clinical, endoscopic and histological presentation. However the presence of dysplasia must have an attentive monitoring.

Plasma lactate concentration as a predictor of gastric necrosis and survival among dogs with gastric dilatation-volvulus: 102 cases (1995-1998).

PubMed

de Papp, E; Drobatz, K J; Hughes, D

1999-07-01

To determine relationships between plasma lactate concentration and gastric necrosis and between plasma lactate concentration and outcome for dogs with gastric dilatation-volvulus. Retrospective study. 102 dogs. Information on signalment, history, plasma lactate concentration, medical and surgical treatment, cost of hospitalization, and outcome was retrieved from medical records. 69 of 70 (99%) dogs with plasma lactate concentration < 6.0 mmol/L survived, compared with 18 of 31 (58%) dogs with plasma lactate concentration > 6.0 mmol/L (1 dog euthanatized for economic reasons was not included). Gastric necrosis was identified in 38 (37%) dogs. Median plasma lactate concentration in dogs with gastric necrosis (6.6 mmol/L) was significantly higher than concentration in dogs without gastric necrosis (3.3 mmol/L). Specificity and sensitivity of using plasma lactate concentration (with a cutoff of 6.0 mmol/L) to predict which dogs had gastric necrosis were 88 and 61%, respectively. Sixty-two of 63 (98%) dogs without gastric necrosis survived, compared with 25 of 38 (66%) dogs with gastric necrosis. Preoperative plasma lactate concentration was a good predictor of gastric necrosis and outcome for dogs with GDV. Preoperative measurement of plasma lactate concentration may assist in determining prognosis of dogs with GDV.

Gastroprotective activity of polysaccharide from Hericium erinaceus against ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer, and its antioxidant activities.

PubMed

Wang, Xiao-Yin; Yin, Jun-Yi; Zhao, Ming-Ming; Liu, Shi-Yu; Nie, Shao-Ping; Xie, Ming-Yong

2018-04-15

The gastroprotective activity of Hericium erinaceus polysaccharide was investigated in rats. The antioxidant activities were also evaluated. Pre-treatment of polysaccharide could reduce ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer. The polysaccharide exhibited scavenging activities of 1, 1-diphenyl-2-picryl-hydrozyl and hydroxyl radicals, and ferrous ion-chelating ability. In the pylorus ligation-induced model, gastric secretions (volume of gastric juice, gastric acid, pepsin and mucus) of ulcer rats administrated with polysaccharide were regulated. Levels of tumor necrosis factor-α and interleukins-1β in serum, and myeloperoxidase activity of gastric tissue were reduced, while antioxidant status of gastric tissue was improved. Defensive factors (nitric oxide, prostaglandin E2, epidermal growth factor) in gastric tissue were increased. These results indicate that Hericium erinaceus polysaccharide possess gastroprotective activity, and the possible mechanisms are related to its regulations of gastric secretions, improvements of anti-inflammatory and antioxidant status, as well as increments of defensive factors releases. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inflammation, atrophy, and gastric cancer

PubMed Central

Fox, James G.; Wang, Timothy C.

2006-01-01

The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world’s population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment. PMID:17200707

Risk factors associated with delayed gastric emptying after subtotal gastrectomy with Billroth-I anastomosis using circular stapler for early gastric cancer patients

PubMed Central

Kim, Ki Han; Jung, Ghap Joong

2012-01-01

Purpose Gastric surgery may potentiate delayed gastric emptying. Billroth I gastroduodenostomy using a circular stapler is the most preferable reconstruction method. The purpose of this study is to analyze the risk factors associated with delayed gastric emptying after radical subtotal gastrectomy with Billroth I anastomosis using a stapler for early gastric cancer. Methods Three hundred and seventy-eight patients who underwent circular stapled Billroth I gastroduodenostomy after subtotal gastrectomy due to early gastric cancer were analyzed retrospectively. One hundred and eighty-two patients had Billroth I anastomosis using a 25 mm diameter circular stapler, and 196 patients had anastomosis with a 28 or 29 mm diameter circular stapler. Clinicopathological features and postoperative outcomes were evaluated and compared between the two groups. Delayed gastric emptying was diagnosed by symptoms and simple abdomen X-ray with or without upper gastrointestinal series or endoscopy. Results Postoperative delayed gastric emptying was found in 12 (3.2%) of the 378 patients. Among all the variables, distal margin and circular stapler diameter were significantly different between the cases with delayed gastric emptying and no delayed gastric emptying. There were statistically significant differences in sex, body mass index, comorbidity, complication, and operation type according to circular stapler diameter. In both univariate and multivariate logistic regression analyses, only the stapler diameter was found to be a significant factor affecting delayed gastric emptying (P = 0.040). Conclusion In this study, the circular stapler diameter was one of the most significant predictable factors of delayed gastric emptying for Billroth I gastroduodenostomy. The use of a 28 or 29 mm diameter circular stapler rather than a 25 mm diameter stapler in stapled gastroduodenostomy for early gastric cancer can reduce postoperative delayed gastric emptying associated with anastomosic stenosis

Risk factors associated with delayed gastric emptying after subtotal gastrectomy with Billroth-I anastomosis using circular stapler for early gastric cancer patients.

PubMed

Kim, Ki Han; Kim, Min Chan; Jung, Ghap Joong

2012-11-01

Gastric surgery may potentiate delayed gastric emptying. Billroth I gastroduodenostomy using a circular stapler is the most preferable reconstruction method. The purpose of this study is to analyze the risk factors associated with delayed gastric emptying after radical subtotal gastrectomy with Billroth I anastomosis using a stapler for early gastric cancer. Three hundred and seventy-eight patients who underwent circular stapled Billroth I gastroduodenostomy after subtotal gastrectomy due to early gastric cancer were analyzed retrospectively. One hundred and eighty-two patients had Billroth I anastomosis using a 25 mm diameter circular stapler, and 196 patients had anastomosis with a 28 or 29 mm diameter circular stapler. Clinicopathological features and postoperative outcomes were evaluated and compared between the two groups. Delayed gastric emptying was diagnosed by symptoms and simple abdomen X-ray with or without upper gastrointestinal series or endoscopy. Postoperative delayed gastric emptying was found in 12 (3.2%) of the 378 patients. Among all the variables, distal margin and circular stapler diameter were significantly different between the cases with delayed gastric emptying and no delayed gastric emptying. There were statistically significant differences in sex, body mass index, comorbidity, complication, and operation type according to circular stapler diameter. In both univariate and multivariate logistic regression analyses, only the stapler diameter was found to be a significant factor affecting delayed gastric emptying (P = 0.040). In this study, the circular stapler diameter was one of the most significant predictable factors of delayed gastric emptying for Billroth I gastroduodenostomy. The use of a 28 or 29 mm diameter circular stapler rather than a 25 mm diameter stapler in stapled gastroduodenostomy for early gastric cancer can reduce postoperative delayed gastric emptying associated with anastomosic stenosis or edema with relative safety.

Assessment of Gastric Emptying in Patients with Autoimmune Gastritis.

PubMed

Kalkan, Çağdaş; Soykan, Irfan; Soydal, Çiğdem; Özkan, Elgin; Kalkan, Emra

2016-06-01

Symptoms of patients with autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any delay in gastric emptying of solid food exists in patients with autoimmune gastritis and, if so, to identify the factors that might affect delayed gastric emptying. A total of 165 patients (106 women) diagnosed as having autoimmune gastritis were analyzed by means of a gastric emptying test. All patients underwent a standardized scintigraphic gastric emptying study. Patients with delayed gastric emptying and normal gastric emptying tests were then compared by means of factors that might affect gastric emptying. Also 65 patients with functional dyspepsia who had a gastric emptying study constituted the control group. The median gastric emptying T ½ time was 127.43 min (min-max 50-953) for patients with AIG and 81 min (min-max 21-121.6) for functional dyspepsia patients (p < 0.001), and median percent retention at 2 h was 63.8 versus 20.2 (p < 0.001). In multivariate analysis, parameters that affected gastric emptying T ½ time were found as serum gastrin level (OR 1.002, 95 % CI 1.001-1.004, p < 0.001, chronic inflammation (OR 3.689, 95 % CI 1.44-9.39, p < 0.001), and increase in the degree of the atrophy of the gastric mucosa (OR 8.96, 95 % CI 2.98-26.93, p < 0.001). In patients with autoimmune gastritis, gastric emptying is generally delayed. Autoimmune gastritis is an important etiology to explain the finding of delayed gastric emptying on a radionuclide test. This new finding is likely to be relevant to clinicians when evaluating and initiating appropriate medical treatment for patients with autoimmune gastritis manifesting upper gastrointestinal symptoms.

Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer

PubMed Central

Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Yuan, Yuan

2017-01-01

Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival. PMID:28350854

Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer.

PubMed

Lu, Youzhu; Jing, Jingjing; Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Sun, Mingjun; Yuan, Yuan

2017-01-01

Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival.

Helicobacter pylori Diversity and Gastric Cancer Risk

PubMed Central

2016-01-01

ABSTRACT Gastric cancer is a leading cause of cancer-related death worldwide. Helicobacter pylori infection is the strongest known risk factor for this malignancy. An important goal is to identify H. pylori-infected persons at high risk for gastric cancer, so that these individuals can be targeted for therapeutic intervention. H. pylori exhibits a high level of intraspecies genetic diversity, and over the past two decades, many studies have endeavored to identify strain-specific features of H. pylori that are linked to development of gastric cancer. One of the most prominent differences among H. pylori strains is the presence or absence of a 40-kb chromosomal region known as the cag pathogenicity island (PAI). Current evidence suggests that the risk of gastric cancer is very low among persons harboring H. pylori strains that lack the cag PAI. Among persons harboring strains that contain the cag PAI, the risk of gastric cancer is shaped by a complex interplay among multiple strain-specific bacterial factors as well as host factors. This review discusses the strain-specific properties of H. pylori that correlate with increased gastric cancer risk, focusing in particular on secreted proteins and surface-exposed proteins, and describes evidence from cell culture and animal models linking these factors to gastric cancer pathogenesis. Strain-specific features of H. pylori that may account for geographic variation in gastric cancer incidence are also discussed. PMID:26814181

Stomach (Gastric) Cancer—Patient Version

Cancer.gov

Stomach (gastric) cancer occurs when cancer cells form in the lining of the stomach. Risk factors include smoking, infection with H. pylori bacteria, and certain inherited conditions. Start here to find information on stomach (gastric) cancer treatment, causes and prevention, screening, research, and statistics.

Molecular classification of gastric cancer.

PubMed

Röcken, Christoph

2017-03-01

Gastric cancer is among the most common cancers worldwide. Despite declining incidences, the prognosis remains dismal in Western countries and is better in Asian countries with national cancer screening programs. Complete endoscopic or surgical resection of the primary tumor with or without lymphadenectomy offers the only chance of cure in the early stage of the disease. Survival of more locally advanced gastric cancers was improved by the introduction of perioperative, adjuvant and palliative chemotherapy. However, the identification and usage of novel predictive and diagnostic targets is urgently needed. Areas covered: Recent comprehensive molecular profiling of gastric cancer proposed four molecular subtypes, i.e. Epstein-Barr virus-associated, microsatellite instable, chromosomal instable and genomically stable carcinomas. The new molecular classification will spur clinical trials exploring novel targeted therapeutics. This review summarizes recent advancements of the molecular classification, and based on that, putative pitfalls for the development of tissue-based companion diagnostics, i.e. prevalence of actionable targets and therapeutic efficacy, tumor heterogeneity and tumor evolution, impact of ethnicity on gastric cancer biology, and standards of care in the East and West. Expert commentary: The overall low prevalence of actionable targets and tumor heterogeneity are the two main obstacles of precision medicine for gastric cancer.

Apatinib for the treatment of gastric cancer.

PubMed

Roviello, Giandomenico; Ravelli, Andrea; Fiaschi, Anna Ida; Cappelletti, Maria Rosa; Gobbi, Angela; Senti, Chiara; Zanotti, Laura; Polom, Karol; Reynolds, Andrew R; Fox, Stephen B; Generali, Daniele

2016-08-01

Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2, has demonstrated encouraging anti-cancer activity in gastric cancer within both in vitro and in vivo models. Apatinib's efficacy, tolerability and safety have been evaluated in one Phase II and one Phase III study in metastatic/advanced gastric cancer. In this review, we focus on the mechanism of action of apatinib, its pharmacokinetic profile and its clinical activity in the treatment of advanced/metastatic gastric cancer. Expert commentary: Unfortunately, as yet, there is no definitive biomarker data for apatinib in gastric cancer.

Diagnostic tools for post-gastric bypass hypoglycaemia.

PubMed

Emous, M; Ubels, F L; van Beek, A P

2015-10-01

In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature. © 2015 World Obesity.

Viscous fingering of HCI through gastric mucin

NASA Astrophysics Data System (ADS)

Bhaskar, K. Ramakrishnan; Garik, Peter; Turner, Bradley S.; Bradley, James Douglas; Bansil, Rama; Stanley, H. Eugene; Lamont, J. Thomas

1992-12-01

THE HCI in the mammalian stomach is concentrated enough to digest the stomach itself, yet the gastric epithelium remains undamaged. One protective factor is gastric mucus, which forms a protective layer over the surface epithelium1-4 and acts as a diffusion barrier5,6 Bicarbonate ions secreted by the gastric epithelium7 are trapped in the mucus gel, establishing a gradient from pH 1-2 at the lumen to pH 6-7 at the cell surface8-10. How does HCI, secreted at the base of gastric glands by parietal cells, traverse the mucus layer without acidifying it? Here we demonstrate that injection of HCI through solutions of pig gastric mucin produces viscous fingering patterns11-18 dependent on pH, mucin concentration and acid flow rate. Above pH 4, discrete fingers are observed, whereas below pH 4, HCI neither penetrates the mucin solution nor forms fingers. Our in vitro results suggest that HCI secreted by the gastric gland can penetrate the mucus gel layer (pH 5-7) through narrow fingers, whereas HC1 in the lumen (pH 2) is prevented from diffusing back to the epithelium by the high viscosity of gastric mucus gel on the luminal side.

Systematic review: gastric cancer incidence in pernicious anaemia.

PubMed

Vannella, L; Lahner, E; Osborn, J; Annibale, B

2013-02-01

Pernicious anaemia (PA) has an increased risk for gastric cancer (GC). It is not established whether PA patients need to undergo endoscopic/histological follow-up. To provide a systematic overview of the literature on PA and the development of gastric cancer, to estimate the gastric cancer incidence-rate. According to PRISMA, we identified studies on PA patients reporting the incidence of gastric cancer. Quality of studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Meta-analysis on annual gastric cancer incidence rates was performed. Twenty-seven studies met eligibility criteria. 7 studies were of high, 6 of medium, 10 of low and 4 of very low quality. Gastric cancer incidence-rates ranged from 0% to 0.2% per person-years in 7 American, from 0% to 0.5% in 2 Asiatic, from 0% to 1.2% in 11 Northern European studies and from 0% to 0.9% in 7 studies from other European countries. The incidence-rates of gastric cancer ranged from 0% to 1.2% per person-years in studies which used gastroscopy, from 0.1% to 0.9% in those based on International Classification of Disease. Heterogeneity between studies was not statistically significant at the 5% level (Chi-squared test = 17.9, P = 0.08). The calculated pooled gastric cancer incidence-rate was 0.27% per person-years. Meta-analysis showed overall gastric cancer relative risk in PA as 6.8 (95% CI: 2.6-18.1). This systematic review shows a pooled gastric cancer incidence-rate in pernicious anaemia of 0.27% per person-years and an estimated nearly sevenfold relative risk of gastric cancer in pernicious anaemia patients. Further high quality studies are needed to confirm this higher risk. © 2012 Blackwell Publishing Ltd.

Effects of gastric pH on oral drug absorption: In vitro assessment using a dissolution/permeation system reflecting the gastric dissolution process.

PubMed

Kataoka, Makoto; Fukahori, Miho; Ikemura, Atsumi; Kubota, Ayaka; Higashino, Haruki; Sakuma, Shinji; Yamashita, Shinji

2016-04-01

The aim of the present study was to evaluate the effects of gastric pH on the oral absorption of poorly water-soluble drugs using an in vitro system. A dissolution/permeation system (D/P system) equipped with a Caco-2 cell monolayer was used as the in vitro system to evaluate oral drug absorption, while a small vessel filled with simulated gastric fluid (SGF) was used to reflect the gastric dissolution phase. After applying drugs in their solid forms to SGF, SGF solution containing a 1/100 clinical dose of each drug was mixed with the apical solution of the D/P system, which was changed to fasted state-simulated intestinal fluid. Dissolved and permeated amounts on applied amount of drugs were then monitored for 2h. Similar experiments were performed using the same drugs, but without the gastric phase. Oral absorption with or without the gastric phase was predicted in humans based on the amount of the drug that permeated in the D/P system, assuming that the system without the gastric phase reflected human absorption with an elevated gastric pH. The dissolved amounts of basic drugs with poor water solubility, namely albendazole, dipyridamole, and ketoconazole, in the apical solution and their permeation across a Caco-2 cell monolayer were significantly enhanced when the gastric dissolution process was reflected due to the physicochemical properties of basic drugs. These amounts resulted in the prediction of higher oral absorption with normal gastric pH than with high gastric pH. On the other hand, when diclofenac sodium, the salt form of an acidic drug, was applied to the D/P system with the gastric phase, its dissolved and permeated amounts were significantly lower than those without the gastric phase. However, the oral absorption of diclofenac was predicted to be complete (96-98%) irrespective of gastric pH because the permeated amounts of diclofenac under both conditions were sufficiently high to achieve complete absorption. These estimations of the effects of

Do calories or osmolality determine gastric emptying

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

Shafer, R.B.; Levine, A.S.; Marlette, J.M.

1984-01-01

Recent animal studies suggest that gastric emptying is dependent on the caloric and osmotic content of the ingested food. These studies have involved intubation with infusion of liquid meals into the stomach. Scintigraphic methods, which are non-invasive and do not alter normal physiology, are now available for precise quantitation of gastric emptying. To study the role of calories and osmolality on gastric emptying, the authors employed a standardized /sup 99m/Tc-scrambled egg meal washed with 50 cc tap water in 10 normal human volunteers. A variety of simple and complex sugars, non-absorbable complex carbohydrate (polycose), medium chain fatty acid (MCFA) andmore » gluten were dissolved in water and ingested with the test meal. Each subject acted as his own control. Coefficient of variation in control tests in each subject 12 weeks apart was 9.9%. Results showed that incremental glucose (25-66 gm) produced a linear increase in gastric emptying (T/2 control 50 +- 3, 25 gm 60 +- 3, 50 gm 79 +- 3 and 66 gm 102 +- 3 minutes). 25 gm fructose (T/2 59 +- 3 minutes) and 25 gm polycose (T/2 59 +- 3 minutes) had similar effects to glucose. 25 gm sucrose and 25 gm gluten did not significantly differ from controls. MCFA had an effect similar to 50 gm glucose - suggesting that calories are important in gastric emptying. However, 25 gm xylose markedly prolonged gastric emptying to 80 +- 5 minutes. The rank order for osmolality for substances tested MCFA = gluten < polycose < polycose < fructose < sucrose = glucose < xylose defined no relationship to gastric emptying. The authors' results suggest that neither calories nor osmolality alone determine gastric emptying. A specific food does not necessarily have the same effect on gastric emptying in different individuals.« less

Gastric Transposition for Esophageal Replacement in Children

PubMed Central

Hirschl, Ronald B.; Yardeni, Dani; Oldham, Keith; Sherman, Neil; Siplovich, Leo; Gross, Eitan; Udassin, Raphael; Cohen, Zehavi; Nagar, Hagith; Geiger, James D.; Coran, Arnold G.

2002-01-01

Objective To evaluate the authors’ experience with gastric transposition as a method of esophageal replacement in children with congenital or acquired abnormalities of the esophagus. Summary Background Data Esophageal replacement in children is almost always done for benign disease and thus requires a conduit that will last more than 70 years. The organ most commonly used in the past has been colon; however, most series have been fraught with major complications and conduit loss. For these reasons, in 1985 the authors switched from using colon interpositions to gastric transpositions for esophageal replacement in infants and children. Methods The authors retrospectively reviewed the records of 41 patients with the diagnoses of esophageal atresia (n = 26), corrosive injury (n = 8), leiomyomatosis (n = 5), and refractory gastroesophageal reflux (n = 2) who underwent gastric transposition for esophageal replacement. Results Mean ± SE age at the time of gastric transposition was 3.3 ± 0.6 years. All but two transpositions were performed through the posterior mediastinum without mortality or loss of the gastric conduit despite previous surgery on the gastric fundus in 8 (20%), previous esophageal operations in 15 (37%), and previous esophageal perforations in 6 (15%) patients. Complications included esophagogastric anastomotic leak (n = 15, 36%), which uniformly resolved without intervention; stricture formation (n = 20, 49%), all of which no longer require dilation; and feeding intolerance necessitating jejunal feeding (n = 8, 20%) due to delayed gastric emptying (n = 3), feeding aversion related to the underlying anomaly (n = 1), or severe neurological impairment (n = 4). No redo anastomoses were required. Conclusions Gastric transposition reestablishes effective gastrointestinal continuity with few complications. Oral feeding and appropriate weight gain are achieved in most children. Therefore, gastric transposition is an appropriate alternative for esophageal

64Cu DOTA-Trastuzumab PET/CT in Studying Patients With Gastric Cancer

ClinicalTrials.gov

2017-12-11

Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IA Gastric Cancer; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

Immunomodulatory Effect of H. Pylori CagA Genotype and Gastric Hormones On Gastric Versus Inflammatory Cells Fas Gene Expression in Iraqi Patients with Gastroduodenal Disorders.

PubMed

Al-Ezzy, Ali Ibrahim Ali

2016-09-15

To evaluate the Immunomodulatory effects of CagA expression; pepsinogen I, II & gastrin-17 on PMNs and lymphocytes Fas expression in inflammatory and gastric cells; demographic distribution of Fas molecule in gastric tissue and inflammatory cells. Gastroduodenal biopsies were taken from 80 patients for histopathology and H. pylori diagnosis. Serum samples were used for evaluation of pepsinogen I (PGI); (PGII); gastrin-17 (G-17). Significant difference (p < 0.001) in lymphocytes & PMNs Fas expression; epithelial & lamina propria Fas localization among H. pylori associated gastric disorders. No correlation between grade of lymphocytes & PMNs Fas expression in gastric epithelia; lamina propria and types of gastric disorder. Significant difference (p < 0.001) in total gastric Fas expression, epithelial Fas; lamina propria and gastric gland Fas expression according to CagA , PGI; PGII; PGI/PGII; Gastrin-17. Total gastric Fas expression has significant correlation with CagA , PGII levels. Gastric epithelial and gastric lamina propria Fas expression have significant correlation with CagA , PGI; PGII levels. Significant difference (p < 0.001) was found in lymphocytes & PMNs Fas expression; epithelial & lamina propria localization of lymphocytes & PMNs Fas expression according to CagA , PGI; PGII; PGI/PGII; Gastrin-17. Lymphocytes Fas expression have correlation with PGI, PGII, PGI/PGII. PMNs Fas expression have correlation with PGI, PGII. Fas gene expression and localization on gastric and inflammatory cells affected directly by H. pylori CagA and indirectly by gastric hormones. This contributes to progression of various gastric disorders according to severity of CagA induced gastric pathology and gastric hormones disturbance throughout the course of infection and disease.

Importance of Second-look Endoscopy on an Empty Stomach for Finding Gastric Bezoars in Patients with Gastric Ulcers.

PubMed

Iwamuro, Masaya; Tanaka, Shouichi; Moritou, Yuki; Inaba, Tomoki; Higashi, Reiji; Kusumoto, Chiaki; Yunoki, Naoko; Ishikawa, Shin; Okamoto, Yuko; Kawai, Yoshinari; Kitada, Ken-Ichi; Takenaka, Ryuta; Toyokawa, Tatsuya; Okada, Hiroyuki

2017-06-01

　Most gastric bezoars can be treated with endoscopic fragmentation combined with or without cola dissolution, whereas laparotomy or laparoscopic surgery is generally inevitable for small intestinal bezoars because they cause small bowel obstruction. Therefore, early diagnosis and management of gastric bezoars are necessary to prevent bezoar-induced ileus. To investigate the incidence of overlooked gastric bezoars during the initial esophagogastroduodenoscopy, we retrospectively reviewed the cases of 27 patients diagnosed with gastrointestinal bezoars. The bezoars were diagnosed using esophagogastroduodenoscopy (n=25), abdominal ultrasonography (n=1), and barium follow-through examination (n=1). Bezoars were overlooked in 9/25 patients (36.0%) during the initial endoscopy examination because the bezoars were covered with debris in the stomach. Of the 9 patients, 8 had concomitant gastric ulcers, and the other patient had gastric lymphoma. Although a computed tomography (CT) scan was performed before the second-look endoscopy in 8 of the 9 patients, the bezoars were mistaken as food debris on CT findings and were overlooked in these patients. In conclusion, gastric bezoars may not be discovered during the initial esophagogastroduodenoscopy and CT scan. In cases with debris in the stomach, second-look endoscopy is essential to detect bezoars.

[Simplified laparoscopic gastric bypass. Initial experience].

PubMed

Hernández-Miguelena, Luis; Maldonado-Vázquez, Angélica; Cortes-Romano, Pablo; Ríos-Cruz, Daniel; Marín-Domínguez, Raúl; Castillo-González, Armando

2014-01-01

Obesity surgery includes various gastrointestinal procedures. Roux-en-Y gastric bypass is the prototype of mixed procedures being the most practiced worldwide. A similar and novel technique has been adopted by Dr. Almino Cardoso Ramos and Dr. Manoel Galvao called "simplified bypass," which has been accepted due to the greater ease and very similar results to the conventional technique. The aim of this study is to describe the results of the simplified gastric bypass for treatment of morbid obesity in our institution. We performed a descriptive, retrospective study of all patients undergoing simplified gastric bypass from January 2008 to July 2012 in the obesity clinic of a private hospital in Mexico City. A total of 90 patients diagnosed with morbid obesity underwent simplified gastric bypass. Complications occurred in 10% of patients; these were more frequent bleeding and internal hernia. Mortality in the study period was 0%. The average weight loss at 12 months was 72.7%. Simplified gastric bypass surgery is safe with good mid-term results and a loss of adequate weight in 71% of cases.

Clinical Features and Outcomes of Gastric Ischemia.

PubMed

Sharma, Ayush; Mukewar, Saurabh; Chari, Suresh T; Wong Kee Song, Louis M

2017-12-01

Gastric ischemia is a rare condition associated with poor prognosis. Our study aim was to highlight the clinical features and outcomes of patients with gastric ischemia. A retrospective review of patients diagnosed with isolated gastric ischemia at our institution from January 1, 2000, to May 5, 2016, was performed. Demographic, clinical, endoscopic, radiologic, and outcome variables were abstracted for analysis. Seventeen patients (65% men) with mean age of 69.3 ± 11.3 years and body mass index of 28.8 ± 11.1 were identified. The etiologies for gastric ischemia included local vascular causes (n = 8), systemic hypoperfusion (n = 4), and mechanical obstruction (n = 5). The most common presenting symptoms were abdominal pain (65%), gastrointestinal bleeding (47%), and altered mental status (23%). The typical endoscopic appearance was mucosal congestion and erythema with or without ulceration. Gastric pneumatosis and portal venous air were more commonly seen on CT imaging. Radiologic and/or surgical intervention was needed in 9 patients, while the remaining 8 patients were managed conservatively with acid suppression, antibiotics, and nasogastric tube decompression. The median duration of hospital stay was 15 days (range 1-36 days). There were no cases of rebleeding and the mortality rate as a direct result of gastric ischemia was 24% within 6 months of diagnosis. Although uncommon, gastric ischemia is associated with significant mortality. Endoscopy and CT imaging play an important role in its diagnosis. The management of gastric ischemia is dictated by its severity and associated comorbidities.

Laparoscopic Band-Separated One Anastomosis Gastric Bypass.

PubMed

Ospanov, Oral B

2016-09-01

This video demonstrates laparoscopic band-separated one anastomosis gastric bypass-combining the advantages of banding and gastric bypass without stapler and cutter use. This is basically a gastrojejunal loop bypass above an obstructive band in the upper stomach. An adjustable low pressure "Medsil" gastric band was introduced in the abdomen and retracted through the retrogastric tunnel. The front wall of the stomach below the band was displaced in the upward direction through the ring band, increasing the size of the anterior portion of the stomach pouch so that a gastroenteroanastomosis could be created at this point. Gastro-gastric sutures were placed to create a gastro-gastric plication around the band and hold it in position. The band tubing was exteriorized and connected to a special port, which was secured to the abdominal wall fascia. A jejunal loop was created about 200 cm from the ligament of Treitz and anastomosed to the gastric pouch by hand using Vicryl 2/0 sutures. Between November 2015 and February 2016, the study was performed on 10 patients. The average operating time for all cases was 75 min (range 63-87). There was no morbidity or mortality. No complications were observed, including band erosion and band infection. Operation costs were about $2000 lower with this method than with standard gastric bypass surgery. Postop the patients lost weight by 3-4 kg per month. Preliminary results show that laparoscopic band-separated one anastomosis gastric bypass have feasibility, safety, efficacy, and reduced operating costs.

Clinical outcomes of endoscopic submucosal dissection for early gastric cancer in remnant stomach or gastric tube.

PubMed

Nishide, N; Ono, H; Kakushima, N; Takizawa, K; Tanaka, M; Matsubayashi, H; Yamaguchi, Y

2012-06-01

Little information exists regarding the optimal treatment of early gastric cancer (EGC) in a remnant stomach or gastric tube. The aim of this study was to assess the feasibility and clinical outcomes of endoscopic submucosal dissection (ESD) for EGC in a remnant stomach and gastric tube. Between September 2002 and December 2009, ESD was performed in 62 lesions in 59 patients with EGC in a remnant stomach (48 lesions) or gastric tube (14 lesions). Clinicopathological data were retrieved retrospectively to assess the en bloc resection rate, complications, and outcomes. Treatment results were assessed according to the indications for endoscopic resection, and were compared with those of ESD performed in a whole stomach during the same study period. The en bloc resection rates for lesions within the standard and expanded indication were 100 % and 93 %, respectively. Postoperative bleeding occurred in five patients (8 %). The perforation rate was significantly higher (18 %, 11 /62) than that of ESD in a whole stomach (5 %, 69 /1479). Among the perforation cases, eight lesions involved the anastomotic site or stump line, and ulcerative changes were observed in five lesions. The 3-year overall survival rate was 85 %, with eight deaths due to other causes and no deaths from gastric cancer. A high en bloc resection rate was achieved by ESD for EGC in a remnant stomach or gastric tube; however, this procedure is still technically demanding due to the high complication rate of perforation. © Georg Thieme Verlag KG Stuttgart · New York.

The Incidence of Gastric Metaplasia in Patients with Duodenal Ulcer*

PubMed Central

Min, Young II; Lee, Byoung Wook; Chang, Young Woon; Chi, Hyun Sook; Lee, Jung Kook

1987-01-01

To investigate the incidence of duodenal gastric metaplasia and its underlying gastric or duodenal diseases, the authors obtained endoscopic biopsy specimens from the duodenal bulb at random sites during endoscopy from 19 normal subjects, 11 patients with gastric ulcer, 18 with duodenal and/or prepyloric ulcer (s), 7 with duodenitis and 8 with gastric erosions. The biopsy specimens were assessed with PAS staining to confirm gastric metaplasia. The incidence of duodenal gastric metaplasia was 72.2% in patients with duodenal and/or prepyloric ulcer (s), which contrasted with the patients with gastric ulcers (36.4%), duodenitis (42.9%), gastric erosions (12.5%), and normal subjects (5.3%). In conclusion, the results suggest that gastric metaplasia seen predominantly in patients with duodenal ulcer, seems to be related to hyperacidity and it plays some role in the pathogenesis of peptic ulcer in duodenum. PMID:3154823

Molecular classification of gastric cancer: a new paradigm.

PubMed

Shah, Manish A; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y; Klimstra, David S; Gerdes, Hans; Kelsen, David P

2011-05-01

Gastric cancer may be subdivided into 3 distinct subtypes--proximal, diffuse, and distal gastric cancer--based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 85% of samples were classified correctly. Gene set analysis with the false discovery rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Subtypes of gastric cancer that have epidemiologic and histologic distinctions are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. ©2011 AACR.

Molecular Classification of Gastric Cancer: A new paradigm

PubMed Central

Shah, Manish A.; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y.; Klimstra, David S.; Gerdes, Hans; Kelsen, David P.

2011-01-01

Purpose Gastric cancer may be subdivided into three distinct subtypes –proximal, diffuse, and distal gastric cancer– based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >85% of samples were classified correctly. Gene set analysis with the False Discovery Rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. PMID:21430069

Molecular pathology of gastric cancer: research and practice.

PubMed

Yasui, Wataru; Sentani, Kazuhiro; Sakamoto, Naoya; Anami, Katsuhiro; Naito, Yutaka; Oue, Naohide

2011-10-15

Recent advances in the understanding of molecular stomach carcinogenesis are reviewed. As to molecular events in individual mucin phenotypes of gastric cancer, the CDX2-Reg IV-SOX9 pathway is associated with the intestinal mucin phenotype, while OLFM4 and CLDN18 are novel markers for the gastric phenotype. microRNAs play an important role in epigenetic deregulation in gastric cancer. Many microRNAs are up-regulated and down-regulated, and some of these are associated with histological differentiation and cancer progression. Reduced miR-200 may participate in the genesis of diffuse type gastric cancer by reducing E-cadherin expression. Genetic polymorphism is a crucial endogenous cause and a fundamental factor of cancer risk. PSCA polymorphism alters the susceptibility to diffuse type gastric cancer through modulation of cell proliferation activity. Cancer stem cells possess the capacity for self-renewal and cause the heterogeneous lineages of cancer cells. Cancer stem cells also show resistance to anti-tumor chemotherapy. Only a minor population of gastric cancer cells reveals the properties of cancer stem cells, and CD44 is one of the markers for gastric cancer stem cells. The origin of gastric cancer stem cells remains to be elucidated. Copyright © 2011 Elsevier GmbH. All rights reserved.

Vection-induced gastric dysrhythmias and motion sickness

NASA Technical Reports Server (NTRS)

Koch, K. L.; Stern, R. M.

1986-01-01

Gastric electrical and mechanical activity during vection-induced motion sickness was investigated. The contractile events of the antrum and gastric myoelectric activity in healthy subjects exposed to vection were measured simultaneously. Symptomatic and myoelectric responses of subjects with vagotomy and gastric resections during vection stimuli were determined. And laboratory based computer systems for analysis of the myoelectric signal were developed. Gastric myoelectric activity was recorded from cutaneous electrodes, i.e., electrogastrograms (EGGs), and antral contractions were measured with intraluminal pressure transducers. Vection was induced by a rotating drum. gastric electromechanical activity was recorded during three periods: 15 min baseline, 15 min drum rotation (vection), and 15 to 30 min recovery. Preliminary results showed that catecholamine responses in nauseated versus symptom-free subjects were divergent and pretreatment with metoclopramide HC1 (Reglan) prevented vection-induced nausea and reduced tachygastrias in two previously symptomatic subjects.

Successful treatment with a combination of endoscopic injection and irrigation with coca cola for gastric bezoar-induced gastric outlet obstruction.

PubMed

Lin, Chen-Sheng; Tung, Chun-Fang; Peng, Yen-Chun; Chow, Wei-Keung; Chang, Chi-Sen; Hu, Wei-Hsiung

2008-01-01

We report a case of gastric bezoar-induced gastric outlet obstruction that was successfully treated with a combination of endoscopic injection and irrigation with Coca Cola. A 73-year-old diabetic woman had a history of perforated peptic ulcer and had received pyloroplasty more than 20 years previously. She had been ingesting Pho Pu Zi (Cordia dichotoma Forst. f.) as an appetizer for 1 month. She presented with epigastric pain, nausea, and vomiting. Upper gastrointestinal endoscopy, performed at a local hospital, showed 2 gastric bezoars in the stomach, and 1 of them impacted at the pylorus. She was referred to our emergency department for removal of the gastric bezoars that were suspected to be causing gastric outlet obstruction. All attempts at endoscopic removal using a polypectomy snare, biopsy forceps and Dormia basket failed. We then injected Coca Cola directly into the bezoar mass, followed by irrigation with Coca Cola. Follow-up endoscopy was performed the next day, which revealed that the gastric bezoars had dissolved spontaneously.

Telomerase activity in gastric cancer.

PubMed

Hiyama, E; Yokoyama, T; Tatsumoto, N; Hiyama, K; Imamura, Y; Murakami, Y; Kodama, T; Piatyszek, M A; Shay, J W; Matsuura, Y

1995-08-01

Although many genetic alterations have been reported in gastric cancer, it is not known whether all gastric tumors are capable of indefinite proliferative potential, e.g., immortality. The expression of telomerase and stabilization of telomeres are concomitant with the attainment of immortality in tumor cells; thus, the measurement of telomerase activity in clinically obtained tumor samples may provide important information useful both as a diagnostic marker to detect immortal cancer cells in clinical materials and as a prognostic indicator of patient outcome. Telomerase activity was analyzed in 66 primary gastric cancers with the use of a PCR-based assay. The majority of tumors (85%) displayed telomerase activity, but telomerase was undetectable in 10 tumors (15%), 8 of which were early stage tumors. Most of the tumors with telomerase activity were large and of advanced stages, including metastases. Survival rate of patients of tumors with detectable telomerase activity was significantly shorter than that of those without telomerase activity. Alterations of telomere length (reduced/elongated terminal restriction fragments) were detected in 14 of 66 (21%) gastric cancers, and all 14 had telomerase activity. Cellular DNA contents revealed that all 22 aneuploid tumors had detectable telomerase activity. The present results indicate that telomerase activation may be required as a critical step in the multigenetic process of tumorigenesis, and that telomerase is frequently but not always activated as a late event in gastric cancer progression.

Inhibition of gastric secretion in treatment of pancreatic insufficiency.

PubMed Central

Saunders, J H; Drummond, S; Wormsley, K G

1977-01-01

The content of pancreatic enzymes in the duodenum was studied in two patients with pancreatic achylia after a standard meal supplemented with commercial pancreatic extract. Gastric transit of the enzymes, with appearance of near-normal amounts in the duodenal contents, occurred only after inhibition of gastric secretion and buffering of residual gastric acid with antacids. Gastric inhibition and neutralisation of acid are therefore necessary for the satisfactory treatment of patients with pancreatic exocrine insufficiency but normal gastric function. PMID:13906

Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling

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

Kirman, Christopher R., E-mail: ckirman@summittoxi

To extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs.more » Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (< 0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment. - Highlights: • SIDMS allows for measurement of Cr(VI) reduction rate in gastric fluid ex vivo • Human gastric fluid has three reducing pools • Cr(VI) in drinking water at < 0.7 mg/L is rapidly reduced in human gastric fluid • Reduction rate is concentration- and pH-dependent • A refined

Estrogen receptors in gastric cancer: Advances and perspectives.

PubMed

Ur Rahman, Muhammad Saif; Cao, Jiang

2016-02-28

Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of the development and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future

Gastric cancer research in Mexico: a public health priority.

PubMed

Sampieri, Clara Luz; Mora, Mauricio

2014-04-28

This study aimed review studies conducted on Mexican patients diagnosed with gastric cancer and/or diseases associated with its development, in which at least one Mexican institute has participated, and to assess their contributions to the primary and secondary prevention of this disease. A search of the Medline database was conducted using the following keywords: gastric/stomach cancer, Mexico. Studies of the Mexican population were selected in which at least one Mexican Institute had participated and where the findings could support public policy proposals directed towards the primary or secondary prevention of gastric cancer. Of the 148 studies found in the Medline database, 100 were discarded and 48 were reviewed. According to the analysis presented, these studies were classified as: epidemiology of gastric cancer (5/48); risk factors and protectors relating to gastric cancer (9/48); relationship between Helicobacter pylori and pathologies associated with gastric cancer and the development of the disease (16/48); relationship between the Epstein-Barr virus and pathologies associated with gastric cancer and the development of the disease (3/48); molecular markers for the development of diseases associated with gastric cancer and gastric cancer (15/48). Mexico requires a program for the prevention and control of gastric cancer based on national health indicators. This should be produced by a multidisciplinary committee of experts who can propose actions that are relevant in the current national context. The few studies of gastric cancer conducted on the Mexican population in national institutes highlight the poor connection that currently exists between the scientific community and the health sector in terms of resolving this health issue. Public policies for health research should support projects with findings that can be translated into benefits for the population. This review serves to identify national research groups studying gastric cancer in the Mexican

Gastric cancer research in Mexico: A public health priority

PubMed Central

Sampieri, Clara Luz; Mora, Mauricio

2014-01-01

This study aimed review studies conducted on Mexican patients diagnosed with gastric cancer and/or diseases associated with its development, in which at least one Mexican institute has participated, and to assess their contributions to the primary and secondary prevention of this disease. A search of the Medline database was conducted using the following keywords: gastric/stomach cancer, Mexico. Studies of the Mexican population were selected in which at least one Mexican Institute had participated and where the findings could support public policy proposals directed towards the primary or secondary prevention of gastric cancer. Of the 148 studies found in the Medline database, 100 were discarded and 48 were reviewed. According to the analysis presented, these studies were classified as: epidemiology of gastric cancer (5/48); risk factors and protectors relating to gastric cancer (9/48); relationship between Helicobacter pylori and pathologies associated with gastric cancer and the development of the disease (16/48); relationship between the Epstein-Barr virus and pathologies associated with gastric cancer and the development of the disease (3/48); molecular markers for the development of diseases associated with gastric cancer and gastric cancer (15/48). Mexico requires a program for the prevention and control of gastric cancer based on national health indicators. This should be produced by a multidisciplinary committee of experts who can propose actions that are relevant in the current national context. The few studies of gastric cancer conducted on the Mexican population in national institutes highlight the poor connection that currently exists between the scientific community and the health sector in terms of resolving this health issue. Public policies for health research should support projects with findings that can be translated into benefits for the population. This review serves to identify national research groups studying gastric cancer in the Mexican

Laparoscopic Conversion of One Anastomosis Gastric Bypass to a Standard Roux-en-Y Gastric Bypass.

PubMed

Amor, Imed Ben; Petrucciani, Niccolo; Kassir, Radwan; Al Munifi, Abdullah; Piche, Thierry; Debs, Tarek; Gugenheim, Jean

2017-05-01

One anastomosis gastric bypass (OAGB) demonstrated results similar to traditional Roux-en-Y procedures [1-3], in terms of weight loss and resolution of obesity-related comorbidities. The main controversy regarding OAGB is the concern for an association between biliary alkaline gastritis and esophageal or gastric cancer raised by some studies [4]. We present the case of a 51-year-old woman with a BMI of 41 kg/m2 who underwent a laparoscopic OAGB in 2014. One year later, she consulted for recurrent heartburns. An upper GI endoscopy showed pouchitis and bile reflux in the esophagus. Medical treatment of gastroesophageal reflux disease was ineffective. We decided to convert the OAGB to a Roux-en-Y gastric bypass (RYGB). In this video, we show how to revise an OAGB to treat chronic bile reflux, by converting the procedure to a standard RYGB. The intervention starts by restoring the normal anatomy of the small bowel, with the resection of the gastrojejunal anastomosis, which was located at 250-cm du Treitz's ligament. Then, the gastric pouch is created. A standard Roux-en-Y gastric bypass is performed. The resection of the gastrojejunal anastomosis allows fashioning the Roux-en-Y limb with the classical measures. This technique allows a conversion to a standard RYGB and is effective in treating the biliary reflux.

Surgical Scales: Primary Closure versus Gastric Resection for Perforated Gastric Ulcer - A Surgical Debate.

PubMed

Gachabayov, Mahir; Babyshin, Valentin; Durymanov, Oleg; Neronov, Dmitriy

2017-01-01

Perforated gastric ulcer is one of the most life-threatening complications of peptic ulcer disease with high morbidity and mortality rates. The surgical strategy for gastric perforation in contrast with duodenal perforations often requires consilium and intraoperative debates. The subject of the debate is a 59-year-old male patient who presented with perforated giant gastric ulcer complicated by generalized peritonitis and severe sepsis. The debate is based on a systematized table dividing all factors into three groups and putting them on surgical scales. Pathology-related factors influencing the decision-making are size and site of perforation, local tissue inflammation, signs of malignancy, simultaneous complications of peptic ulcer, peritonitis, and sepsis. Besides these factors, patient- and healthcare-related factors should also be considered.

Surgical Scales: Primary Closure versus Gastric Resection for Perforated Gastric Ulcer - A Surgical Debate

PubMed Central

Gachabayov, Mahir; Babyshin, Valentin; Durymanov, Oleg; Neronov, Dmitriy

2017-01-01

Perforated gastric ulcer is one of the most life-threatening complications of peptic ulcer disease with high morbidity and mortality rates. The surgical strategy for gastric perforation in contrast with duodenal perforations often requires consilium and intraoperative debates. The subject of the debate is a 59-year-old male patient who presented with perforated giant gastric ulcer complicated by generalized peritonitis and severe sepsis. The debate is based on a systematized table dividing all factors into three groups and putting them on surgical scales. Pathology-related factors influencing the decision-making are size and site of perforation, local tissue inflammation, signs of malignancy, simultaneous complications of peptic ulcer, peritonitis, and sepsis. Besides these factors, patient- and healthcare-related factors should also be considered. PMID:28584503

Polyamines are Inhibitors of Gastric Acid Secretion

NASA Astrophysics Data System (ADS)

Ray, Tushar K.; Nandi, Jyotirmoy; Pidhorodeckyj, Nykolai; Meng-Ai, Zhou

1982-03-01

The naturally occurring organic polycations such as spermine and spermidine inhibit histamine-stimulated gastric acid secretion by bullfrog gastric mucosa in vitro; spermine is much more potent than spermidine. Unlike the H2 receptor antagonists, the polyamines are completely ineffective from the nutrient side and are effective only from the secretory side of the chambered mucosa. The polyamine effects could be reversed by increasing K+ concentration in the secretory solution. Studies with isolated gastric microsomal vesicles demonstrate that the polyamines do not inhibit the gastric H+,K+-ATPase but greatly decrease the ATPase-mediated uptake of H+ under appropriate conditions. For the latter effects the presence of polyamine within the vesicle interior was found to be essential. Our data strongly suggest an uncoupling of the gastric H+,K+-ATPase system by the polyamines. The therapeutic potential of these and similar compounds in the treatment of hyperacidity and peptic ulcer is discussed.

Measurement of gastric emptying by intragastric gamma scintigraphy.

PubMed

Malbert, C H; Mathis, C; Bobillier, E; Laplace, J P; Horowitz, M

1997-09-01

Gastric emptying is usually measured in animals and humans by dilution/sampling or external scintigraphy. These methods are either time consuming or require expensive equipment. The capacity of a miniature gamma counter positioned in the stomach to measure emptying of liquid and solid meals was evaluated. In eight conscious pigs fitted with gastric and duodenal cannulae, gastric emptying of saline (500 mL), dextrose (20%, 500 mL), porridge (300 g) and scrambled eggs (300 g), all labelled with 3.5 MBq 99mTC, was evaluated. When positioned in the antrum the probe was unable to quantify gastric emptying. In contrast, measurements of the fractional emptying of saline over 4-min periods by the probe positioned in the corpus and quantification of radioactivity in the duodenal effluent correlated closely (r = 0.88, P < 0.05). Gastric emptying (50% emptying time) of saline and both solid meals measured by the probe was not significantly different from quantification of the duodenal effluent volume. No difference was observed also for the dextrose meal but only while gastric acid secretion was suppressed by omeprazole. We conclude that an intragastric gamma counter permits measurement of gastric emptying of homogeneous meals provided meal stimulation of gastric secretion was not extensive. This was possible probably by monitoring emptying from the proximal stomach.

Multi-disciplinary team for early gastric cancer diagnosis improves the detection rate of early gastric cancer.

PubMed

Di, Lianjun; Wu, Huichao; Zhu, Rong; Li, Youfeng; Wu, Xinglong; Xie, Rui; Li, Hongping; Wang, Haibo; Zhang, Hua; Xiao, Hong; Chen, Hui; Zhen, Hong; Zhao, Kui; Yang, Xuefeng; Xie, Ming; Tuo, Bigung

2017-12-06

Gastric cancer is a frequent malignant tumor worldwide and its early detection is crucial for curing the disease and enhancing patients' survival rate. This study aimed to assess whether the multi-disciplinary team (MDT) can improve the detection rate of early gastric cancer (EGC). The detection rate of EGC at the Digestive Endoscopy Center, Affiliated Hospital, Zunyi Medical College, China between September 2013 and September 2015 was analyzed. MDT for the diagnosis of EGC in the hospital was established in September 2014. The study was divided into 2 time periods: September 1, 2013 to August 31, 2014 (period 1) and September 1, 2014 to September 1, 2015 (period 2). A total of 60,800 patients' gastroscopies were performed during the two years. 61 of these patients (0.1%) were diagnosed as EGC, accounting for 16.44% (61/371) of total patients with gastric cancer. The EGC detection rate before MDT (period 1) was 0.05% (16/29403), accounting for 9.09% (16/176) of total patients with gastric cancer during this period. In comparison, the EGC detection rate during MDT (period 2) was 0.15% (45/31397), accounting for 23% (45/195) of total patients with gastric cancer during this period (P < 0.05). Univariate and multivariate logistic analyses showed that intensive gastroscopy for high risk patients of gastric cancer enhanced the detection rate of EGC in cooperation with Department of Pathology (OR = 10.1, 95% CI 2.39-43.3, P < 0.05). MDT could improve the endoscopic detection rate of EGC.

Gastric washing by distilled water can reduce free gastric cancer cells exfoliated into the stomach lumen.

PubMed

Ohki, Atsuko; Abe, Nobutsugu; Yoshimoto, Eri; Hashimoto, Yoshikazu; Takeuchi, Hirohisa; Nagao, Gen; Masaki, Tadahiko; Mori, Toshiyuki; Ohkura, Yasuo; Sugiyama, Masanori

2018-04-25

Intragastric free cancer cells in patients with gastric cancer have rarely been studied. The purpose of this study was to investigate the detection rate of intragastric free cancer cells in gastric washes using two types of solutions during endoscopic examination. We further clarified risk factors affecting the presence of exfoliated free cancer cells. A total of 175 patients with gastric cancer were enrolled. Lactated Ringer's solution (N = 89) or distilled water (DW; N = 86) via endoscopic working channel was sprayed onto the tumor surface, and the resultant fluid was collected for cytological examination. We compared the cancer-cell positivity rate between the two (Ringer and DW) groups. We also tested the correlation between cancer-cell positivity and clinicopathological factors in the Ringer group to identify risk factors for the presence of exfoliated cancer cells. The cancer-cell positivity rate was significantly higher in the Ringer group than that in the DW group (58 vs 6%). Cytomorphology in the Ringer group was well maintained, but not in the DW group. The larger tumor size (≥ 20 mm) and positive lymphatic involvement were significant risk factors of exfoliated free cancer cells. Cancer cells can be highly exfoliated from the tumor surface into the gastric lumen by endoscopic irrigation in large gastric cancer with lymphatic involvement. Gastric washing by DW can lead to cytoclasis of free cancer cells; therefore, it may minimize the possibility of cancer-cell seeding in procedures carrying potential risks of tumor-cell seeding upon transluminal communication, such as endoscopic full-thickness resection and laparoscopy-endoscopy cooperative surgery.

E-Cadherin and Gastric Cancer: Cause, Consequence, and Applications

PubMed Central

Liu, Xin

2014-01-01

E-cadherin (epithelial-cadherin), encoded by the CDH1 gene, is a transmembrane glycoprotein playing a crucial role in maintaining cell-cell adhesion. E-cadherin has been reported to be a tumor suppressor and to be down regulated in gastric cancer. Besides genetic mutations in CDH1 gene to induce hereditary diffuse gastric cancer (HDGC), epigenetic factors such as DNA hypermethylation also contribute to the reduction of E-cadherin in gastric carcinogenesis. In addition, expression of E-cadherin could be mediated by infectious agents such as H. pylori (Helicobacter pylori). As E-cadherin is vitally involved in signaling pathways modulating cell proliferation, survival, invasion, and migration, dysregulation of E-cadherin leads to dysfunction of gastric epithelial cells and contributes to gastric cancer development. Moreover, changes in its expression could reflect pathological conditions of gastric mucosa, making its role in gastric cancer complicated. In this review, we summarize the functions of E-cadherin and the signaling pathways it regulates. We aim to provide comprehensive perspectives in the molecular mechanism of E-cadherin and its involvement in gastric cancer initiation and progression. We also focus on its applications for early diagnosis, prognosis, and therapy in gastric cancer in order to open new avenues in this field. PMID:25184143

Lauren classification and individualized chemotherapy in gastric cancer.

PubMed

Ma, Junli; Shen, Hong; Kapesa, Linda; Zeng, Shan

2016-05-01

Gastric cancer is one of the most common malignancies worldwide. During the last 50 years, the histological classification of gastric carcinoma has been largely based on Lauren's criteria, in which gastric cancer is classified into two major histological subtypes, namely intestinal type and diffuse type adenocarcinoma. This classification was introduced in 1965, and remains currently widely accepted and employed, since it constitutes a simple and robust classification approach. The two histological subtypes of gastric cancer proposed by the Lauren classification exhibit a number of distinct clinical and molecular characteristics, including histogenesis, cell differentiation, epidemiology, etiology, carcinogenesis, biological behaviors and prognosis. Gastric cancer exhibits varied sensitivity to chemotherapy drugs and significant heterogeneity; therefore, the disease may be a target for individualized therapy. The Lauren classification may provide the basis for individualized treatment for advanced gastric cancer, which is increasingly gaining attention in the scientific field. However, few studies have investigated individualized treatment that is guided by pathological classification. The aim of the current review is to analyze the two major histological subtypes of gastric cancer, as proposed by the Lauren classification, and to discuss the implications of this for personalized chemotherapy.

13C-sodium acetate breath test for evaluation of gastric emptying times in dogs with gastric dilatation-volvulus.

PubMed

Schmitz, S; Jansen, N; Failing, K; Neiger, R

2013-01-01

The aim of the study was to assess solid phase gastric emptying via non-invasive 13C-sodium acetate breath test in large breed dogs with or without gastric dilatation-volvulus (GDV). Dogs were recruited into one of the following groups: group 1 = healthy large breed dogs with no history of GDV, group 2 = dogs that underwent elective abdominal surgery for reasons unrelated to the gastrointestinal tract, and group 3 = dogs that underwent laparotomy and gastropexy to correct GDV. The dogs were fed a test meal containing 100 mg 13C-sodium acetate (for group 2 and 3, this was < 48 hours post-operatively). Breath samples were obtained at baseline and every 30 minutes for 3 hours, then every hour for a total of 7 hours. 12CO2/13CO2 ratio was measured for each breath sample via non-dispersive infrared spectroscopy and 25%, 50% and 75% gastric emptying times were calculated and compared between groups. Gastric emptying times were significantly prolonged in dogs undergoing surgery (group 2) compared to group 1 and 3. Also, gastric emptying times of dogs with GDV were significantly prolonged compared to controls, but not to the same extent as dogs in group 2. There was a significant effect of abdominal surgery on gastric emptying times. Surprisingly, dogs after GDV surgery and gastropexy had shorter gastric emptying times than dogs undergoing laparotomy for reasons other than GDV, but still prolonged compared to healthy controls. The reason for these differences requires further study.

Updates on esophageal and gastric cancers.

PubMed

Gallo, Amy; Cha, Charles

2006-05-28

Esophageal and gastric cancers are both common and deadly. Patients present most often after disease progression and survival is therefore poor. Due to demographic variability and recent changes in disease incidence, much emphasis has been placed on studying risk factors for both esophageal and gastric cancers. However, with increasing understanding of these diseases, low survival rates persist and continued intensive studies are necessary to optimize treatment plans. This review article discusses updates in the evolving epidemiology, clinical presentation, risk factors, and diagnostic and treatment modalities of esophageal and gastric cancers.

Lymphatic mapping for gastric adenocarcinoma.

PubMed

Hundley, Jon C; Shen, Perry; Shiver, Stephen A; Geisinger, Kim R; Levine, Edward A

2002-11-01

The role of lymphadenectomy for gastric carcinoma has been debated for decades. Lymphatic mapping has revolutionized the treatment of melanoma and breast cancer. However, its potential utility in guiding lymphadenectomy for gastric carcinoma is unknown. Therefore we initiated a trial to investigate lymphatic mapping for gastric carcinoma at Wake Forest University Baptist Medical Center. Lymphatic mapping for gastric carcinoma was attempted in 14 cases of gastric carcinoma. Mapping was performed by perilesional injection of isosulfan blue and the first node in the draining basin was harvested and sent fresh to pathology. Sentinel lymph nodes (SLNs) were evaluated by hematoxylin and eosin (H&E) staining. Immunohistochemical analysis was performed on all SLNs that were found to be negative on initial histologic studies. Radical gastrectomy with celiac node dissection was performed in all cases. SLNs were identified in 14 cases. In one case the technique was abandoned because of bulk nodal disease. The average number of SLNs found in each case was 2.8 with a range of one to five. Eight of 14 patients were found to have SLNs positive for metastatic carcinoma. In seven of these patients pathologic analysis of the final resection specimen confirmed the presence of nodal disease. In one case carcinoma was found in a SLN on touch preparation and no nodal disease was noted in the resection specimen. Immunohistochemical studies performed on SLNs found to be negative on initial H&E histologic analysis failed to reveal the presence of carcinoma. The overall sensitivity and specificity were found to be 72.7 and 75 per cent, respectively. Lymphatic mapping is technically possible in the setting of gastric carcinoma and SLNs can be successfully identified in the majority of cases. Upstaging occurred in one case which may have ramifications for adjuvant therapy. SLN positivity accurately predicts the presence of additional nodal disease beyond the SLN in the final resection

[Regulation of moxibustion for expression of gastric mucosa cell-related marker protein in rats with acute gastric ulcer].

PubMed

Yang, Zong-Bao; Wang, Chen-Guang; Gong, An; Xie, Yu-feng; Liu, Qiong; Yang, Qing

2013-11-01

To explore relevant material basis of moxibustion for recovering gastric mucosal lesion. METHODL Forty-five SD rats were randomly divided into a normal goup, a model group, an acupoint group and a control group, 15 rats in the model group and 10 rats in the rest three groups. Except the normal group, binding and cold stress method were used to establish gastric mucosa injury model. The suspended moxibustion was applied in the acupoint group and control group at acupoints of the stomach meridian ("Liangmen" (ST 21) and "Zusanli" (ST36) and control acupoints (Laterally 1cm next to the "Liangmen" (ST 21) and Zusanli" (ST36), once a day, consectutively for 12 days. After 12 days, morphology of gastric mucosal was observed under optical microscope; protein fingerprints of gastric mucosa cell in rats were detected by protein fingerprint technology, weak cation chip and weak anion chip. Also mass to charge ratio of differential proteins in groups were compared and analyzed. Compared with the model group, index of gastric mucosal lesion in the acupoint group was reduced and its morphology was obviously improved (P<0.05). Campared with control group, index and morphology of gastric mucosal lesion were significantly improved in the acupoint group (P<0.05). According to test of weak cation chip, there was four marker proteins that had expression differences, indicating moxibustion at acupoints of stomach meridian could inrease expression of three marker protein whose molecular weight was 1354Da, 5692Da and 8432Da (all P<0.05) while reduce expression of marker protein with molecular weight of 3287Da (_<0.05). According to test of weak anion chip, moxibustion at acupoints of stomach meridian could increase expression of three marker proteins whose molecular weight was 2412 Da, 3026Da and 6475 Da (allP<0.05). Moxibustion at acupoints of the stomach meridian could regulate differential expression of gastric mucosa cell-related marker protein in rats with acute gastric ulcer and

A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions.

PubMed

Xu, Z-q; Broza, Y Y; Ionsecu, R; Tisch, U; Ding, L; Liu, H; Song, Q; Pan, Y-y; Xiong, F-x; Gu, K-s; Sun, G-p; Chen, Z-d; Leja, M; Haick, H

2013-03-05

Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints. Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry. Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared

Gastric dilatation-volvulus in dogs.

PubMed

Broome, C J; Walsh, V P

2003-12-01

Gastric dilatation-volvulus (GDV) is a disease in which there is gross distension of the stomach with fluid or gas and gastric malpositioning. It causes pathology of multiple organ systems and is rapidly fatal. It is common in large- and giant-breed dogs. The disease appears to have a familial predisposition. Thoracic depth/width ratio also appears to predispose dogs to GDV. Implicated dietary factors include dietary particle size, frequency of feeding, speed of eating, aerophagia and an elevated feed bowl. A fearful temperament and stressful events may also predispose dogs to GDV. Abdominal distension, non-productive retching, restlessness, signs of shock, tachypnoea and dyspnoea are possible clinical signs. Initial treatment includes treatment of shock and gastric decompression. Surgical treatment should be performed promptly. There are no studies comparing the use of different anaesthetic agents in the anaesthetic management of GDV. Pre-medication with an opioid/benzodiazepine combination has been recommended. Induction agents that cause minimal cardiovascular changes such as opioids, neuroactive steroidal agents and etomidate are recommended. Anaesthesia should be maintained with an inhalational agent. Surgical therapy involves decompression, correction of gastric malpositioning, debridement of necrotic tissue, and gastropexy. Options for gastropexy include incisional, tube, circumcostal, belt-loop, incorporating, and laparoscopic gastropexy. Expected mortality with surgical therapy is 15-24%. Prognostic factors include mental status on presentation, presence of gastric necrosis, presence of cardiac arrhythmia and plasma lactate levels. Prophylactic gastropexy should be considered in dogs identified as being at high risk.

Advanced endoscopic imaging in gastric neoplasia and preneoplasia

PubMed Central

Lee, Jonathan W J; Lim, Lee Guan; Yeoh, Khay Guan

2017-01-01

Conventional white light endoscopy remains the current standard in routine clinical practice for early detection of gastric cancer. However, it may not accurately diagnose preneoplastic gastric lesions. The technological advancements in the field of endoscopic imaging for gastric lesions are fast growing. This article reviews currently available advanced endoscopic imaging modalities, in particular chromoendoscopy, narrow band imaging and confocal laser endomicroscopy, and their corresponding evidence shown to improve diagnosis of preneoplastic gastric lesions. Raman spectrometry and polarimetry are also introduced as promising emerging technologies. PMID:28176895

Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: A novel gastroprotective mechanism independent of gastric acid suppression.

PubMed

Mazumder, Somnath; De, Rudranil; Sarkar, Souvik; Siddiqui, Asim Azhar; Saha, Shubhra Jyoti; Banerjee, Chinmoy; Iqbal, Mohd Shameel; Nag, Shiladitya; Debsharma, Subhashis; Bandyopadhyay, Uday

2016-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O 2 - ) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H 2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid secretion but offered gastroprotection by preventing DCF-induced generation of O 2 - due to mitochondrial respiratory chain failure and by preventing mitochondrial oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF-stimulated reduced fatty acid oxidation, mitochondrial depolarization and bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling through NF-κB by DCF. Furthermore, mitoTEMPO when administered in rats with preformed gastric lesions expedited the healing of gastric injury and the healed stomach exhibited its normal physiology as evident from gastric acid and pepsin secretions under basal or stimulated conditions. Thus, in contrast to the existing antiulcer drugs, mitochondrially targeted O 2 - scavengers like mitoTEMPO may represent a novel class of gastroprotective molecules that does not affect gastric acid secretion and may be used in combination with DCF, keeping its anti-inflammatory action intact, while reducing its gastrodamaging effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Epstein–Barr Virus Infection and Gastric Cancer

PubMed Central

Chen, Xin-Zu; Chen, Hongda; Castro, Felipe A.; Hu, Jian-Kun; Brenner, Hermann

2015-01-01

Abstract Epstein–Barr virus (EBV) infection is found in a subset of gastric cancers. Previous reviews have exclusively focused on EBV-encoded small RNA (EBER) positivity in gastric cancer tissues, but a comprehensive evaluation of other type of studies is lacking. We searched the PubMed database up to September, 2014, and performed a systematic review. We considered studies comparing EBV nucleic acids positivity in gastric cancer tissue with positivity in either adjacent non-tumor tissue of cancer patients or non-tumor mucosa from healthy individuals, patients with benign gastric diseases, or deceased individuals. We also considered studies comparing EBV antibodies in serum from cancer patients and healthy controls. Selection of potentially eligible studies and data extraction were performed by 2 independent reviewers. Due to the heterogeneity of studies, we did not perform formal meta-analysis. Forty-seven studies (8069 cases and 1840 controls) were identified. EBER positivity determined by in situ hybridization (ISH) was significantly higher in cancer tissues (range 5.0%–17.9%) than in adjacent mucosa from the same patients or biopsies from all control groups (almost 0%). High EBV nuclear antigen-1 (EBNA-1) positivity by PCR was found in gastric cancer tissues, but most were not validated by ISH or adjusted for inflammatory severity and lymphocyte infiltration. Only 4 studies tested for EBV antibodies, with large variation in the seropositivities of different antibodies in both cases and controls, and did not find an association between EBV seropositivity and gastric cancer. In summary, tissue-based ISH methods strongly suggest an association between EBV infection and gastric cancer, but PCR method alone is invalid to confirm such association. Very limited evidence from serological studies and the lack of novel antibodies warrant further investigations to identify potential risk factors of EBV for gastric cancer. PMID:25997049

Current issues and future perspectives of gastric cancer screening

PubMed Central

Hamashima, Chisato

2014-01-01

Gastric cancer remains the second leading cause of cancer death worldwide. About half of the incidence of gastric cancer is observed in East Asian countries, which show a higher mortality than other countries. The effectiveness of 3 new gastric cancer screening techniques, namely, upper gastrointestinal endoscopy, serological testing, and “screen and treat” method were extensively reviewed. Moreover, the phases of development for cancer screening were analyzed on the basis of the biomarker development road map. Several observational studies have reported the effectiveness of endoscopic screening in reducing mortality from gastric cancer. On the other hand, serologic testing has mainly been used for targeting the high-risk group for gastric cancer. To date, the effectiveness of new techniques for gastric cancer screening has remained limited. However, endoscopic screening is presently in the last trial phase of development before their introduction to population-based screening. To effectively introduce new techniques for gastric cancer screening in a community, incidence and mortality reduction from gastric cancer must be initially and thoroughly evaluated by conducting reliable studies. In addition to effectiveness evaluation, the balance of benefits and harms must be carefully assessed before introducing these new techniques for population-based screening. PMID:25320514

Ranitidine: forgotten drug of delayed gastric emptying.

PubMed

Veevers, Abbie E; Oxberry, Stephen G

2017-09-01

Delayed gastric emptying in the presence or absence of mechanical bowel obstruction can cause distressing symptoms in palliative care patients. We present two patients, both with vomiting due to delayed gastric emptying and gastric outlet obstruction secondary to pancreatic cancer, treated with subcutaneous ranitidine resulting in a symptomatic response. We hypothesise that ranitidine is a useful adjunct to standard treatment with prokinetic agents or octreotide in such patients and potentially those with proximal mechanical bowel obstruction from other malignancies with associated delayed gastric emptying. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Abnormalities in gastric mechanic sensitivity, gastric emptying and electrogastrography in non organic dyspepsia (NOD)].

PubMed

López Gastón, A; López DeLuise, G A; Sarmiento, A; Andrusch, A

1997-01-01

The aim was to study the alterations in mechanosensitivity, gastric emptying, and electrogastrography (E.G.G.) in a population of patients suffering from N.O.D. eighteen controls (9 males, 9 females, mean age 49.33 years old < SEM 3.62, range 24-74) and 32 patients with N.O.D. (22 males, 21 females, mean age 55.72 years old, SEM 2.87, range 17-86) were studied. Gastric mechano-sensitivity with a latex balloon of low compliance inflated "in phasic" was investigated, and intra balloon pressure was recorded. Gastric emptying with a mixed meal marked with 99 Tc in the solid phase, containing 250 Cal, was studied. E.G.G. was studied using two skin surface electrodes Ag-2C1Ag placed on epigastric area following a probalistic antral axe. Only dominant frequency in each block was considered, and % of total abnormalities on total recording time lesser than 2 c.p.m or more than 4 c.p.m. was considered. Recordings were taken during fast time during 30 minutes, and 30 minutes after a meal containing 250 Cal. Analysis with F.F.T, and spectral running. In 67.92% a delay in gastric emptying was observed. 56.3% did not complete 700 ml. of balloon inflation because of pain, Vs 16.8% in controls (p < 0.001) The slopes of intra-balloon pressure were not different in both groups. (Variance, F-NS). Mean E.C.A was 2.99 c.p.m in control, Vs 3.46 in fasting and 3.64 in postprandial period in N.O.D. (p = NS) Differences in fasting and postprandial % of arrhythmias total time recording were significant in N.O.D. ("t". 0.02 > p 0.01). Twenty percent of controls showed isolated tachygastria, but dominant frequencies never were higher than 6 c.p.m and never last more than 8% of the total recording time. Sixty eight point seventy five percent of N.O.D. showed arrhythmias. 48% of tachygastrias were in the range 30-60% of total recording time. No differences in gastric emptying between patient presenting pain with = < 700 ml. and < 700 ml. of balloon inflation were seen. Patients with sensorial

Guilty as charged: bugs and drugs in gastric ulcer.

PubMed

Sontag, S J

1997-08-01

Gastric ulcer disease remains a cause of hemorrhage, perforation, outlet obstruction, and death. Recent advances in the understanding of peptic ulcer disease indicate that infection with Helicobacter pylori and ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) are the cause of almost all gastric and duodenal ulcers. Our therapy, therefore, is in a state of transition: the old acid-suppressive temporary therapy that allows frequent ulcer recurrences and complications is being replaced by curative therapies. The old therapy, by reducing gastric acid secretion or enhancing gastric mucosal defenses, inhibited the cofactors needed for ulcer development. Acid suppression relieved symptoms and healed ulcers, while defense enhancers, such as prostaglandin analogs healed and prevented acute NSAID-induced gastric ulcers. These benefits were maintained, however, only as long as acid-reducing agents or mucosal defense enhancers were continued. On the other hand, curative therapies (such as eradicating H. pylori infection and/or stopping the use of NSAIDs) eliminate the causes of ulcer. Curative combination regimens consisting of antibiotics, ranitidine bismuth citrate, bismuth, and proton pump inhibitors have been approved by the Food and Drug Administration. These new regimens can cure benign gastric ulcer. Unfortunately, we cannot always determine which gastric ulcers are benign, and concern about gastric cancer remains. All gastric ulcers therefore still require biopsy and histological examination. With new treatment regimens, the time may be rapidly approaching when ulcer disease will be "history."

Prognostic significance of aberrant gene methylation in gastric cancer.

PubMed

Shi, Jing; Zhang, Guanjun; Yao, Demao; Liu, Wei; Wang, Na; Ji, Meiju; He, Nongyue; Shi, Bingyin; Hou, Peng

2012-01-01

Promoter methylation acts as an important alternative to genetic alterations for gene inactivation in gastric carcinogenesis. Although a number of gastric cancer-associated genes have been found to be methylated in gastric cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. In the present study, we used methylation-specific PCR (MSP) to analyze promoter methylation of 9 gastric cancer-associated genes, including MLF1, MGMT, p16, RASSF2, hMLH1, HAND1, HRASLS, TM, and FLNc, and their association with clinicopathological characteristics and clinical outcome in a large cohort of gastric cancers. Our data showed that all of these genes were aberrantly methylated in gastric cancer, ranging from 8% to 51%. Moreover, gene methylation was strongly associated with certain clinicopathological characteristics, such as tumor differentiation, lymph node metastasis, and cancer-related death. Of interest, methylation of MGMT, p16, RASSF2, hMLH1, HAND1, and FLNc was closely associated with poor survival in gastric cancer, particularly MGMT, p16, RASSF2 and FLNc. Thus, our findings suggested these epigenetic events may contribute to the initiation and progression of gastric cancer. Importantly, methylation of some genes were closely relevant to poor prognosis in gastric cancer, providing the strong evidences that these hypermethylated genes may be served as valuable biomarkers for prognostic evaluation in this cancer.

Prognostic significance of aberrant gene methylation in gastric cancer

PubMed Central

Shi, Jing; Zhang, Guanjun; Yao, Demao; Liu, Wei; Wang, Na; Ji, Meiju; He, Nongyue; Shi, Bingyin; Hou, Peng

2012-01-01

Promoter methylation acts as an important alternative to genetic alterations for gene inactivation in gastric carcinogenesis. Although a number of gastric cancer-associated genes have been found to be methylated in gastric cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. In the present study, we used methylation-specific PCR (MSP) to analyze promoter methylation of 9 gastric cancer-associated genes, including MLF1, MGMT, p16, RASSF2, hMLH1, HAND1, HRASLS, TM, and FLNc, and their association with clinicopathological characteristics and clinical outcome in a large cohort of gastric cancers. Our data showed that all of these genes were aberrantly methylated in gastric cancer, ranging from 8% to 51%. Moreover, gene methylation was strongly associated with certain clinicopathological characteristics, such as tumor differentiation, lymph node metastasis, and cancer-related death. Of interest, methylation of MGMT, p16, RASSF2, hMLH1, HAND1, and FLNc was closely associated with poor survival in gastric cancer, particularly MGMT, p16, RASSF2 and FLNc. Thus, our findings suggested these epigenetic events may contribute to the initiation and progression of gastric cancer. Importantly, methylation of some genes were closely relevant to poor prognosis in gastric cancer, providing the strong evidences that these hypermethylated genes may be served as valuable biomarkers for prognostic evaluation in this cancer. PMID:22206050

21 CFR 862.1320 - Gastric acidity test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... and treatment of patients with peptic ulcer, Zollinger-Ellison syndrome (peptic ulcer due to gastrin... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gastric acidity test system. 862.1320 Section 862....1320 Gastric acidity test system. (a) Identification. A gastric acidity test system is a device...

21 CFR 862.1320 - Gastric acidity test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and treatment of patients with peptic ulcer, Zollinger-Ellison syndrome (peptic ulcer due to gastrin... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gastric acidity test system. 862.1320 Section 862....1320 Gastric acidity test system. (a) Identification. A gastric acidity test system is a device...

Postoperative fever predicts poor prognosis of gastric cancer.

PubMed

Feng, Fan; Tian, Yangzi; Yang, Xuewen; Sun, Li; Hong, Liu; Yang, Jianjun; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

2017-09-22

Data about prognostic value of postoperative fever in gastric cancer was lacking. Thus, the present study aims to investigate the prognostic value of postoperative fever in gastric cancer. From September 2008 to March 2015, 2938 gastric cancer patients were enrolled in the present study. Clinicopathological features were recoded. The association between postoperative fever and prognosis of gastric cancer were analyzed. There were 2294 male (78.1%) and 644 female (21.9%). Seven hundred and fifty-six patients suffered from fever. Among them, the duration of fever less than 48h occurred in 508 cases, and duration of fever over 48h occurred in 248 cases. Univariate and multivariate analysis showed that postoperative fever was an independent risk factor for prognosis of gastric cancer ( P < 0.001). For the entire cohort, duration of fever over 48h was significantly associated with decreased survival ( P < 0.001). In subgroup analysis, duration of fever over 48h was significantly associated with poor prognosis of stage I and II gastric cancer (both P < 0.001). However, postoperative fever was not associated with the prognosis of stage III gastric cancer ( P = 0.334). Considering the type of gastrectomy, postoperative fever was not associated with the prognosis of patients with proximal ( P = 0.318) and distal gastrectomy ( P = 0.806), but duration of fever over 48h was significantly associated with poor prognosis of patients with total gastrectomy ( P = 0.004). In conclusion, postoperative fever was associated with poor prognosis of gastric cancer.

Association of Helicobacter pylori infection with gastric cancer.

PubMed

Alexander, G A; Brawley, O W

2000-01-01

Helicobacter pylori has generated public health interest since its identification in 1983. Past studies have suggested that the bacterium plays a role in the pathogenesis of gastric cancer. More recent studies support the conclusion that the association of H. pylori with gastric cancer is causal. The purpose of this article is to review the available evidence supporting the association of H. pylori with gastric cancer. We performed a critical review of the relevant literature published in the English language on H. pylori and gastric cancer using MEDLINE, Index Medicus for the years 1985 to 1997. The reference lists of selected articles also were reviewed to capture citations for further pertinent studies. H. pylori is thought to be the major cause of chronic atrophic gastritis. H. pylori gastritis is worldwide in distribution. H. pylori is now categorized by the International Agency for Cancer Research as a group 1 carcinogen, i.e., an agent that is carcinogenic to humans. Several reports from the United States have found the highest frequencies of gastric cancer in geographic areas and populations with the highest rates of acquisition of H. pylori infection. The high prevalence of H. pylori infection has been documented most notably in blacks and Hispanics, who also are at high risk for gastric cancer. New studies that focus on the epidemiology and pathology of H. pylori improve our understanding of its relationship with gastric cancer and advance the development of gastric cancer prevention and control strategies that are proposed.

Gastric Helicobacter species as a cause of feline gastric lymphoma: A viable hypothesis

PubMed Central

Bridgeford, Erin C.; Marini, Robert P.; Feng, Yan; Parry, Nicola M.A.; Rickman, Barry; Fox, James G.

2009-01-01

Gastric Helicobacter spp. are associated with chronic inflammation and neoplastic transformation in humans as well as domestic and laboratory species. The present study examined the association of Helicobacter heilmannii (Hhe) infection in pet cats with feline gastric mucosa associated lymphoid tissue (MALT) lymphoma. Tissues were collected via gastric biopsy or at necropsy from 47 pet cats with clinical signs of gastrointestinal disease, including vomiting and inappetance, and classified as gastritis (14/47), lymphoma (31/37), or normal (2/47). Tissues positive for argyrophilic organisms with Warthin–Starry stain (29/47) were assessed by fluorescent in situ hybridization (FISH) for the presence of Hhe strains 1–4 as well as with a fifth probe that detected Helicobacter salomonis, Helicobacter bizzozeronii, or Helicobacter felis. A significant association of positive Warthin–Starry status with Hhe infection was found in cases of sick cats (22/29; p < 0.05 by Chi-square; χ2 = 7.034). Interestingly, a significant association between Hhe status and a diagnosis of lymphoblastic or lymphocytic lymphoma was observed as well in a subset of 24 Warthin–Starry positive lymphoma cases: of lymphoblastic lymphoma cases, 13/17 were positive for Hhe ( p < 0.05; χ2 = 4.854). Hhe strains 2 and 4 were most commonly found (18/29 and 17/29, respectively) among sick cats, although a higher than expected number of cats was also positive for Hhe1, which initial reports have described as rare in cats and common in humans. The association found between a positive Hhe status with the presence of feline gastric lymphoma, especially lymphoblastic lymphoma, argues for the need to conduct prospective studies to better identify the frequency and strain distribution of Hhe infection in both healthy and clinically ill cats, particularly those cats with gastric lymphoma. PMID:18387674

Glycoprofiling of Early Gastric Cancer Using Lectin Microarray Technology.

PubMed

Li, Taijie; Mo, Cuiju; Qin, Xue; Li, Shan; Liu, Yinkun; Liu, Zhiming

2018-01-01

Recently, studies have reported that protein glycosylation plays an important role in the occurrence and development of cancer. Gastric cancer is a common cancer with high morbidity and mortality owing to most gastric cancers are discovered only at an advanced stage. Here, we aim to discover novel specific serum glycanbased biomarkers for gastric cancer. A lectin microarray with 50 kinds of tumor-associated lectin was used to detect the glycan profiles of serum samples between early gastric cancer and healthy controls. Then lectin blot was performed to validate the differences. The result of the lectin microarray showed that the signal intensities of 13 lectins showed significant differences between the healthy controls and early gastric cancer. Compared to the healthy, the normalized fluorescent intensities of the lectins PWA, LEL, and STL were significantly increased, and it implied that their specifically recognized GlcNAc showed an especially elevated expression in early gastric cancer. Moreover, the binding affinity of the lectins EEL, RCA-II, RCA-I, VAL, DSA, PHA-L, UEA, and CAL were higher in the early gastric cancer than in healthy controls. These glycan structures containing GalNAc, terminal Galβ 1-4 GlcNAc, Tri/tetraantennary N-glycan, β-1, 6GlcNAc branching structure, α-linked fucose residues, and Tn antigen were elevated in gastric cancer. While the two lectins CFL GNL reduced their binding ability. In addition, their specifically recognized N-acetyl-D-galactosamine structure and (α-1,3) mannose residues were decreased in early gastric cancer. Furthermore, lectin blot results of LEL, STL, PHA-L, RCA-I were consistent with the results of the lectin microarray. The findings of our study clarify the specific alterations for glycosylation during the pathogenesis of gastric cancer. The specific high expression of GlcNAc structure may act as a potential early diagnostic marker for gastric cancer.

Development of gastric cancer associated with Helicobacter pylori infection.

PubMed

Sugiyama, Toshiro

2004-09-01

Helicobacter pylori infection is associated with histological gastritis, gastric atrophy, gastric cancer and mucosa-associated lymphoid tissue lymphoma in the stomach. However, gastric cancer only develops in a minority of infected individuals. Such clinical diversity is caused by variations in the interactions between H. pylori pathogenicity, host susceptibility, and environmental factors. Based on evidence from three prospective epidemiological studies, the International Agency for Research on Cancer and the World Health Organization (IARC/WHO) concluded in 1994 that H. pylori has a causal linkage to gastric carcinogenesis and is a definite carcinogen in humans. Two large-scale, prospective, epidemiological studies have recently been reported in Japan and have confirmed that H. pylori infection constitutes a high risk factor for the development of gastric cancer, at least in males. In order to obtain evidence that eradication of H. pylori leads to a reduction in the occurrence of gastric cancer, reversibility of precancerous lesions, gastric atrophy or intestinal metaplasia should be proven after eradication treatment. A biopsy specimen from the lesser curvature of the corpus is the most sensitive for evaluating the regression of gastric atrophy on histology, and the evaluation needs be conducted at least 13 months after treatment. In a Mongolian gerbil model with or without low-dose chemical carcinogens, it has been demonstrated that H. pylori can lead to the development of gastric cancer. Experimental studies have elucidated that virulence factors of H. pylori interact with gastric epithelial cell signaling related to carcinogenesis. The cag pathogenicity island (cagPAI) is a major virulence gene cluster; it encodes the type IV secretion machinery system forming a cylinder-like structure. The CagA protein is translocated into target cells via this secretion system and induces a hummingbird phenotype, a growth factor-like effect. The other gene products are

Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit.

PubMed

Geyer, Philipp Emanuel; Maak, Matthias; Nitsche, Ulrich; Perl, Markus; Novotny, Alexander; Slotta-Huspenina, Julia; Dransart, Estelle; Holtorf, Anne; Johannes, Ludger; Janssen, Klaus-Peter

2016-05-01

The B-subunit of the bacterial Shiga toxin (STxB), which is nontoxic and has low immunogenicity, can be used for tumor targeting of breast, colon, and pancreatic cancer. Here, we tested whether human gastric cancers, which are among the most aggressive tumor entities, express the cellular receptor of Shiga toxin, the glycosphingolipid globotriaosylceramide (Gb3/CD77). The majority of cases showed an extensive staining for Gb3 (36/50 cases, 72%), as evidenced on tissue sections of surgically resected specimen. Gb3 expression was detected independent of type (diffuse/intestinal), and was negatively correlated to increasing tumor-node-metastasis stages (P = 0.0385), as well as with markers for senescence. Gb3 expression in nondiseased gastric mucosa was restricted to chief and parietal cells at the bottom of the gastric glands, and was not elevated in endoscopic samples of gastritis (n = 10). Gb3 expression in established cell lines of gastric carcinoma was heterogeneous, with 6 of 10 lines being positive, evidenced by flow cytometry. STxB was taken up rapidly by live Gb3-positive gastric cancer cells, following the intracellular retrograde transport route, avoiding lysosomes and rapidly reaching the Golgi apparatus and the endoplasmic reticulum. Treatment of the Gb3-expressing gastric carcinoma cell line St3051 with STxB coupled to SN38, the active metabolite of the topoisomerase type I inhibitor irinotecan, resulted in >100-fold increased cytotoxicity, as compared with irinotecan alone. No cytotoxicity was observed on gastric cancer cell lines lacking Gb3 expression, demonstrating receptor specificity of the STxB-SN38 compound. Thus, STxB is a highly specific transport vehicle for cytotoxic agents in gastric carcinoma. Mol Cancer Ther; 15(5); 1008-17. ©2016 AACR. ©2016 American Association for Cancer Research.

Analyzing the influence of gastric intestinal metaplasia on gastric ulcer healing in Helicobacter pylori-infected patients without atrophic gastritis.

PubMed

Chen, Li-Wei; Chang, Liang-Che; Hua, Chung-Ching; Hsieh, Bor-Jen; Chen, Shuo-Wei; Chien, Rong-Nan

2017-01-03

Gastric epithelial hyper-proliferation was reported in patients with Helicobacter pylori (H. pylori)-infected gastric mucosa with intestinal metaplasia (IM) changes. In patients with gastric ulcer (GU) and IM, the GU may have a different healing rate in comparison to patients without IM. This study aimed to compare the difference in GU healing between H. pylori-infected patients with IM and those without IM. We retrospectively analyzed patients at the Keelung Chung Gung Memorial Hospital during the period from March 2005 to January 2011. The inclusion criteria were: 1) endoscopic findings of GU and biopsy histological examination plus rapid urease test indicating H. pylori infection; 2) gastric IM adjacent to a GU but with no atrophic gastritis changes; 3) patients receiving H. pylori eradication triple therapy and 8 weeks of maintenance therapy with a proton pump inhibitor; and 4) patients receiving follow-up endoscopy within the 3 rd and the 4 th months after treatment. In total, 327 patients with GU and H. pylori infection (136 with IM and 191 without IM) were included. Patients with IM had a higher GU healing rate than those without IM (91.9% vs. 84.3%, P = 0.040). Multivariate logistical regression analysis revealed that failure of H. pylori eradication (Odds = 4.013, 95% CI: 1.840-8.951, P < 0.001) and gastric IM (Odds = 0.369, 95% CI: 0.168-0.812, P = 0.013) were the predictors of non-healing GU following treatment. Patient with gastric IM change may have a higher GU healing rate than those without gastric IM. However, successful H. pylori eradication is a more important factor for GU healing than gastric IM.

Local steroid injection into the artificial ulcer created by endoscopic submucosal dissection for gastric cancer: prevention of gastric deformity.

PubMed

Mori, H; Rafiq, K; Kobara, H; Fujihara, S; Nishiyama, N; Kobayashi, M; Himoto, T; Haba, R; Hagiike, M; Izuishi, K; Okano, K; Suzuki, Y; Masaki, T

2012-07-01

Endoscopic submucosal dissection (ESD) of large gastric lesions results in an extensive artificial ulcer that can lead to marked gastric deformity. The aim of the current study was to evaluate therapeutic efficacy in the prevention of gastric deformity of local triamcinolone acetonide (TCA) injection into the extensive artificial ulcer following ESD. A total of 45 patients who were diagnosed with early gastric cancer were enrolled. Patients were randomly assigned by the sealed-envelope randomization method to either local TCA injections (n = 21) or sham-control (n = 20) groups. Two clips were placed at the two maximum outer edges of the artificial ulcer after the lesion had been resected (Day 0). Local TCA injections were performed on postoperative Day 5 and Day 12. The distance between the two clips was measured by endoscopic measuring forceps on Days 5, 12, 30, and 60. Granulation formation and gastric deformity were evaluated by visual analog scale (VAS) on Days 30 and 60. Local TCA injection did not alter clip-to-clip distance on postoperative Day 60, and formation of flat granulation tissue over the ulcer was followed by regenerative mucosa without any gastric deformity. The sham-control group showed significant shortening of clip-to-clip distance compared with the local steroid-injected group and protruded forms of granulation tissue with mucosal convergence. Histological evaluation revealed prominent growth of neovessels, swelling, and marked increases in endothelial cells in the local steroid-injected group compared with the sham-control group. Local steroid injection into the floor of a post-ESD artificial ulcer promotes the formation of granulation tissue at an early stage of the healing process leading to regeneration of gastric mucosa without mucosal convergence or gastric deformity. © Georg Thieme Verlag KG Stuttgart · New York.

Gastric intestinal metaplasia as detected by a monoclonal antibody is highly associated with gastric adenocarcinoma

PubMed Central

Mirza, Z K; Das, K K; Slate, J; Mapitigama, R N; Amenta, P S; Griffel, L H; Ramsundar, L; Watari, J; Yokota, K; Tanabe, H; Sato, T; Kohgo, Y; Das, K M

2003-01-01

Background: Some forms of gastric intestinal metaplasia (GIM) may be precancerous but the cellular phenotype that predisposes to gastric carcinogenesis is not well characterised. Mucin staining, as a means of differentiating GIM, is difficult. A monoclonal antibody, mAb Das-1 (initially called 7E12H12), whose staining is phenotypically specific to colon epithelium, was used to investigate this issue. Methods: Using mAb Das-1, by a sensitive immunoperoxidase assay, we examined histologically confirmed GIM specimens from two countries, the USA and Japan. A total of 150 patients comprised three groups: group A, GIM (fields away from the cancer area) from patients with gastric carcinoma (n=60); group B, GIM with chronic gastritis (without gastric carcinoma) (n=72); and group C, chronic gastritis without GIM (n=18). Results: Fifty six of 60 (93%) patients with GIM (both goblet and non-goblet metaplastic cells) from group A reacted intensely with mAb Das-1. Cancer areas from the same 56 patients also reacted. In contrast, 25/72 (35%) samples of GIM from patients in group B reacted with mAb Das-1 (group A v B, p<0.0001). None of the samples from group C reacted with the mAb. Conclusions: Reactivity of mAb Das-1 is clinically useful to simplify and differentiate the phenotypes of GIM. The colonic phenotype of GIM, as identified by mAb Das-1, is strongly associated with gastric carcinoma. PMID:12740335

Gastric intestinal metaplasia as detected by a monoclonal antibody is highly associated with gastric adenocarcinoma.

PubMed

Mirza, Z K; Das, K K; Slate, J; Mapitigama, R N; Amenta, P S; Griffel, L H; Ramsundar, L; Watari, J; Yokota, K; Tanabe, H; Sato, T; Kohgo, Y; Das, K M

2003-06-01

Some forms of gastric intestinal metaplasia (GIM) may be precancerous but the cellular phenotype that predisposes to gastric carcinogenesis is not well characterised. Mucin staining, as a means of differentiating GIM, is difficult. A monoclonal antibody, mAb Das-1 (initially called 7E(12)H(12)), whose staining is phenotypically specific to colon epithelium, was used to investigate this issue. Using mAb Das-1, by a sensitive immunoperoxidase assay, we examined histologically confirmed GIM specimens from two countries, the USA and Japan. A total of 150 patients comprised three groups: group A, GIM (fields away from the cancer area) from patients with gastric carcinoma (n=60); group B, GIM with chronic gastritis (without gastric carcinoma) (n=72); and group C, chronic gastritis without GIM (n=18). Fifty six of 60 (93%) patients with GIM (both goblet and non-goblet metaplastic cells) from group A reacted intensely with mAb Das-1. Cancer areas from the same 56 patients also reacted. In contrast, 25/72 (35%) samples of GIM from patients in group B reacted with mAb Das-1 (group A v B, p<0.0001). None of the samples from group C reacted with the mAb. Reactivity of mAb Das-1 is clinically useful to simplify and differentiate the phenotypes of GIM. The colonic phenotype of GIM, as identified by mAb Das-1, is strongly associated with gastric carcinoma.

[A Case of Collision Tumor of Gastric Malignant Lymphoma and Gastric Cancer].

PubMed

Inoue, Keisuke; Fujiwara, Yoshiyuki; Kogata, Shuhei; Kanaizumi, Hirofumi; Fukuda, Shuichi; Takeyama, Hiroshi; Kitani, Kotaro; Tsujie, Masanori; Yukawa, Masao; Wakasa, Tomoko; Ohta, Yoshio; Inoue, Masatoshi

2016-11-01

A 71-year-old man with anemia, weight loss, and loss of appetite was admitted. Ultrasound examination found thickening of the wall of the stomach. A type 3 gastric tumor was detected in the greater curvature of the gastric corpus via upper gastrointestinal endoscopy. Total gastrectomy, transverse colon resection, and Roux-en-Y anastomosis reconstruction was performed. In the postoperative pathological results, adenocarcinoma, tub2, and diffuse large B cell lymphoma collision was found. The patient underwent chemotherapy for malignant lymphoma and although it was a relatively advanced neoplasia, he is alive without a recurrence.

Studies on gastric bicarbonate secretion in man.

PubMed

Forssell, H

1987-01-01

A method for measurement of human basal and stimulated gastric bicarbonate secretion was developed in the present investigation. The mechanisms involved in the regulation of basal, vagus nerve stimulated as well as fundic distension induced bicarbonate secretion were studied. The investigations were performed in healthy subjects and duodenal ulcer patients, the latter group before and/or after a proximal gastric vagotomy operation. Healthy subjects as well as ulcer patients were premedicated with a histamine H2-receptor antagonist and gastric bicarbonate secretion was determined by use of a gastric perfusion system in combination with computerized continuous recordings of pH and PCO2. The contribution of alkaline saliva to the measured gastric bicarbonate secretion was minimized by continuous salivary suction and correction was made for swallowed saliva by measurement of amylase in the gastric aspirate. A high rate of gastric perfusion facilitated the identification of alkaline duodenogastric reflux and also eliminated its influence on the measurement of gastric bicarbonate secretion. Validation of the measuring system by instillation of small amounts of bicarbonate showed a satisfactory correlation between added and recovered bicarbonate in the range of bicarbonate determinations usually recorded. Decreasing intragastric pH to between 3 and 4 converted all secreted bicarbonate into CO2, but did not affect the measured value of bicarbonate secretion. Vagal stimulation accomplished by sham feeding increased gastric bicarbonate secretion in sixteen healthy subjects from 410 +/- 39 mumol/h to 692 +/- 67 mumol/h (mean +/- SEM, p less than 0.001). This response was independent of intragastric pH in the range of 2 to 7. The muscarinic receptor antagonist, benzilonium bromide, almost abolished the sham feeding response while indomethacin left it nearly unchanged. Nine duodenal ulcer patients had identical basal and vagally stimulated bicarbonate output as healthy subjects

Gastric Volvulus in Guinea Pigs: Comparison with Other Species

PubMed Central

Dudley, Emily S; Boivin, Gregory P

2011-01-01

Gastric volvulus has been documented in several species of animals and is associated with high morbidity and mortality. We report 2 cases of gastric volvulus in guinea pigs that died without detection of prior clinical signs. Both guinea pigs were adult female guinea pigs in a breeding colony and had given birth to multiple litters; one was pregnant at the time of death. Gastric rotations of 540° and 360° were identified at necropsy examination. These cases include the first known report of gastric rotation greater than 360° in any species. Although gastric volvulus has been reported to occur in guinea pigs, little is known about its risk factors, etiology, and pathogenesis. We conducted a literature review to compare gastric volvulus between guinea pigs and other species. PMID:21838984

Epidermal growth factor receptor mutation in gastric cancer.

PubMed

Liu, Zhimin; Liu, Lina; Li, Mei; Wang, Zhaohui; Feng, Lu; Zhang, Qiuping; Cheng, Shihua; Lu, Shen

2011-04-01

Epidermal growth factor receptor (EGFR) and Kirsten-RAS (KRAS) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer. We aimed to screen the mutations of both genes in gastric carcinoma to detect the suitability of EGFR TKIs for patients with gastric carcinoma. We screened EGFR mutation in exons 19-21 and KRAS mutation in exon 2 in 58 gastric adenocarcinomas from China using high resolution melting analysis (HRMA). Positive samples were confirmed by DNA sequencing. Three EGFR missense mutations (5.2%) and 22 single nucleotide polymorphisms (SNP, Q787Q, 37.9%) were identified. To our knowledge, we report for the first time three mutation patterns of EGFR, Y801C, L858R and G863D, in gastric carcinoma. Two samples with EGFR mutation were mucinous adenocarcinoma. These three samples were collected from male patients aged over 75 years old. The frequency of KRAS mutation was 10.3% (6/58). The exclusiveness of EGFR and KRAS mutations was proven for the first time in gastric cancer. Gastric carcinoma of the mucinous adenocarcinoma type collected from older male patients may harbour EGFR mutations. The small subset of gastric adenocarcinoma patients may respond to EGFR TKIs.

Gastric band tubing-related complication during pregnancy.

PubMed

Ongso, Yuni F; Beh, Han N

2017-11-01

In the past few decades, laparoscopic adjustable gastric banding is one of the most common bariatric procedures performed to treat morbid obesity. Device-related complication such as connection-tubing problem is rare. Here we present a case of gastric band tubing complication during pregnancy. This case illustrates the need to maintain high index of suspicion of gastric band device-related complication during pregnancy and early referral for bariatric surgical assessment is recommended.

Gastric band tubing-related complication during pregnancy

PubMed Central

Beh, Han N

2017-01-01

Abstract In the past few decades, laparoscopic adjustable gastric banding is one of the most common bariatric procedures performed to treat morbid obesity. Device-related complication such as connection-tubing problem is rare. Here we present a case of gastric band tubing complication during pregnancy. This case illustrates the need to maintain high index of suspicion of gastric band device-related complication during pregnancy and early referral for bariatric surgical assessment is recommended. PMID:29218217

Importance of vagal input in maintaining gastric tone in the dog.

PubMed Central

Azpiroz, F; Malagelada, J R

1987-01-01

1. Using a gastric barostat to quantify variations in gastric tone, we had previously demonstrated that food ingestion or intestinal nutrient perfusion induces gastric relaxation. These data suggested a basal tonic contraction of the stomach during fasting. 2. To determine the role of vagal input in maintaining fasting gastric tone, we prepared two chronic canine models, either isolating both cervical vagal trunks in a cutaneous tunnel or including the supradiaphragmatic vagi within an implanted cooling jacket. In the fasted conscious dogs, we then studied the effect, on gastric tone, of acute and reversible vagal blockade by cooling. 3. Cervical vagal cooling produced a reversible gastric relaxation and increased the heart rate. Supradiaphragmatic vagal cooling produced a similar gastric relaxation without the cardiac effect. 4. Adrenergic blockade did not change either the base-line gastric tone or the cooling-induced relaxation. Adrenaline decreased gastric tone, but vagal cooling still produced a significant relaxation. 5. Atropine alone or combined with adrenergic antagonists produced a gastric relaxation that was not further increased by vagal cooling. Bethanechol increased gastric tone, an effect unchanged by vagal cooling. 6. We conclude that gastric tone during fasting is maintained by a cholinergic input, which is vagally mediated at both the cervical and the supradiaphragmatic levels. Images Fig. 1 PMID:2888879

Quantitative assessment model for gastric cancer screening

PubMed Central

Chen, Kun; Yu, Wei-Ping; Song, Liang; Zhu, Yi-Min

2005-01-01

AIM: To set up a mathematic model for gastric cancer screening and to evaluate its function in mass screening for gastric cancer. METHODS: A case control study was carried on in 66 patients and 198 normal people, then the risk and protective factors of gastric cancer were determined, including heavy manual work, foods such as small yellow-fin tuna, dried small shrimps, squills, crabs, mothers suffering from gastric diseases, spouse alive, use of refrigerators and hot food, etc. According to some principles and methods of probability and fuzzy mathematics, a quantitative assessment model was established as follows: first, we selected some factors significant in statistics, and calculated weight coefficient for each one by two different methods; second, population space was divided into gastric cancer fuzzy subset and non gastric cancer fuzzy subset, then a mathematic model for each subset was established, we got a mathematic expression of attribute degree (AD). RESULTS: Based on the data of 63 patients and 693 normal people, AD of each subject was calculated. Considering the sensitivity and specificity, the thresholds of AD values calculated were configured with 0.20 and 0.17, respectively. According to these thresholds, the sensitivity and specificity of the quantitative model were about 69% and 63%. Moreover, statistical test showed that the identification outcomes of these two different calculation methods were identical (P>0.05). CONCLUSION: The validity of this method is satisfactory. It is convenient, feasible, economic and can be used to determine individual and population risks of gastric cancer. PMID:15655813

Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.

PubMed

Brzozowski, Tomasz; Magierowska, Katarzyna; Magierowski, Marcin; Ptak-Belowska, Agata; Pajdo, Robert; Kwiecien, Slawomir; Olszanecki, Rafal; Korbut, Ryszard

2017-01-01

Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Current standards in the treatment of gastric cancer].

PubMed

Hacker, Ulrich; Lordick, Florian

2015-08-01

Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti-VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of cholelithiasis and cholecystectomy on gastric emptying.

PubMed

Köksoy, F N; Bulut, T; Köse, H; Soybir, G; Yalçin, O; Aker, Y

1994-06-01

In this prospective, clinical study, four groups, each consisting of 12 patients were established to determine how gastric emptying is influenced in cholelithiasis with accompanied flatulent dyspepsia and the relationship of symptoms and gastric emptying after cholecystectomy: group 1--healthy people; group 2--patients with dyspeptic cholelithiasis; group 3--patients with no dyspepsia after cholecystectomy; group 4--patients with dyspepsia after cholecystectomy. Groups are compared according to solid phase gastric emptying scintigraphies performed with Tc 99m sulphur colloid bound with scrambled eggs. Gastric emptying delayed in groups 2 (P < 0.001) and 4 (P < 0.005) postprandially and did not differ in the group 3 (P > 0.005). These results demonstrate that dyspepsia, in cholelithiasis and persisting after cholecystectomy, has a close relation with delay in gastric emptying.

Gastric cancer following highly selective vagotomy.

PubMed Central

Houghton, P. W.; Leaper, D. J.

1987-01-01

A case of gastric cancer occurring seven years after a highly selective vagotomy is described. This operation may not be the appropriate choice for the surgical treatment of gastric ulcers and H2 blockers should be used with caution in these patients. PMID:3671228

Neonatal Intrathoracic Stomach without Gastric Volvulus.

PubMed

Bokka, Sriharsha; Mohanty, Manoj Kumar

2016-10-01

Intrathoracic stomach is a rare and serious congenital abnormality. The anomaly may be complicated by gastric volvulus and can lead to ischemic gastric infarction in the neonate. If diagnosed antenatally, neonatal management can be planned in advance so as to reduce morbidity. This anomaly must be differentiated from the more common congenital diaphragmatic hernia, as associated pulmonary hypoplasia is common in the latter and rare with gastric herniation. We report a case of intrathoracic stomach in a neonate without volvulus, fortunately a rare entity which was managed operatively, and the child has been under regular follow-up.

Gastric mucosal-associated lymphoid tissue lymphoma.

PubMed

Fischbach, Wolfgang

2013-06-01

Gastric marginal zone B-cell lymphoma of mucosal-associated lymphoid tissue (MALT) is the predominant entity within the primary gastrointestinal lymphomas. Helicobacter pylori represents the decisive pathogenetic factor for gastric MALT lymphoma. The goal of treating gastric MALT lymphoma should be complete cure. The first choice of treatment is H pylori eradication. Patients with histologically persistent residual lymphoma after successful H pylori eradication and normalization of endoscopic findings should be managed by a watch-and-wait strategy. Patients who do not respond to H pylori eradication should be referred for radiation or chemotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

Dietary monosodium glutamate enhances gastric secretion.

PubMed

Khropycheva, Raisa; Uneyama, Hisayuki; Torii, Kunio; Zolotarev, Vasiliy

2009-01-01

Dietary L-glutamate (Glu), an amino acid abundant in many foodstuffs in a free form, is able to modulate physiological functions in the stomach, including secretion and motility. Recently, specific receptors for Glu were identified in the apical membrane of chief cells in the lower region of fundic glands and in the somatostatin-secreting D-cell fraction of the gastric mucosa. This Glu-sensing system in the stomach is linked to activation of the vagal afferents. Among 20 kinds of amino acid, luminal Glu alone activated the vagal afferents in the stomach through a paracrine cascade led by nitric oxide and followed by serotonin (5-HT). In dogs with Pavlov pouches, found that supplementation of an amino acid-rich diet lacking Glu with monosodium Glu (MSG) enhanced the secretion of acid, pepsinogen, and fluid. However, MSG did not affect these secretions induced by a carbohydrate-rich diet and it had no effect on basal secretion when MSG was applied alone without the diet. Enhancement of gastric secretion by MSG was abolished by blockage of the gastric afferents using intra-gastric applied lidocaine. This effect of MSG was due in part to stimulation of 5-HT(3) receptors in the gastric mucosa.

Coexistence of gastrointestinal stromal tumors and gastric adenocarcinomas.

PubMed

Yan, Yan; Li, Ziyu; Liu, Yiqiang; Zhang, Lianhai; Li, Jiyou; Ji, Jiafu

2013-04-01

The purpose of this study is to detect the clinicopathology of gastrointestinal stromal tumors (GISTs) occurring synchronously with gastric adenocarcinomas and to unveil the potential underlying relationship between the synchronous GIST and gastric adenocarcinoma. This study included 15 patients with incidental GISTs found during operations for gastric adenocarcinoma and 30 patients who underwent gastrectomy for gastric cancer without discovering GIST between January 2005 and December 2010 at the Beijing Cancer Institute. We collected the clinicopathological data and analyzed the KIT/PDGFRA mutational status of GISTs, corresponding gastric adenocarcinoma specimens, and the normal tissue around the cancer lesions. Additionally, as a control group, the mutational status of the patients with gastric adenocarcinoma and no other tumors was assayed. Overall, 18 GISTs were found in 15 gastric adenocarcinoma patients. Multiple GIST lesions were found in three cases (20 %). The patients' age ranged from 46 to 85 years, with an average of 67.6 years. The average size of the GISTs was 0.85 cm. All mesenchymal lesions showed low proliferative activity, were of low or very low risk, and were identified as CD117-positive by immunostaining. In GIST lesions, mutations in KIT were detected in 7 out of 13 cases, and of these mutations, 6 were found in exon 11 (46.2 %), and 1 was found in exon 9 (7.7 %). A total of five deletions and one point mutation were in exon 11, and one insertion was in exon 9. Mutations were not detected in exon 17 or 13 of KIT. There was no remarkable mutation analyzed in the gastric adenocarcinoma lesions or normal tissues from either the test or control groups. Clinicopathological profiles and molecular analysis of KIT/PDGFRA showed no obvious relationship between gastric cancer and GISTs in tumor genesis, such as similar oncogene mutations.

IKKε and TBK1 expression in gastric cancer.

PubMed

Lee, Seung Eun; Hong, Mineui; Cho, Junhun; Lee, Jeeyun; Kim, Kyoung-Mee

2017-03-07

Inhibitor of kappa B kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IKKs. IKKε and TBK1 share the kinase domain and are similar in their ability to activate the nuclear factor-kappa B signaling pathway. IKKε and TBK1 are overexpressed through multiple mechanisms in various human cancers. However, the expression of IKKε and TBK1 in gastric cancer and their role in prognosis have not been studied.To investigate overexpression of the IKKε and TBK1 proteins in gastric cancer and their relationship with clinicopathologic factors, we performed immunohistochemical staining using a tissue microarray. Tissue microarray samples were obtained from 1,107 gastric cancer patients who underwent R0 gastrectomy with extensive lymph node dissection and adjuvant chemotherapy.We identified expression of IKKε in 150 (13.6%) and TBK1 in 38 (3.4%) gastric cancers. Furthermore, co-expression of IKKε and TBK1 was identified in 1.5% of cases. Co-expression of IKKε and TBK1 was associated with differentiated intestinal histology and earlier T stage. In a multivariate binary logistic regression model, intestinal histologic type by Lauren classification and early AJCC stage were significant predictors for expression of IKKε and TBK1 proteins in gastric cancer. Changes in IKKε and TBK1 expression may be involved in the development of intestinal-type gastric cancer. The overexpression of IKKε and TBK1 should be considered in selected patients with intestinal-type gastric cancer.In conclusion, this is the first large-scale study investigating the relationships between expression of IKKε and TBK1 and clinicopathologic features of gastric cancer. The role of IKKε and TBK1 in intestinal-type gastric cancer pathogenesis should be elucidated by further investigation.

Prevalence of deleterious ATM germline mutations in gastric cancer patients.

PubMed

Huang, Dong-Sheng; Tao, Hou-Quan; He, Xu-Jun; Long, Ming; Yu, Sheng; Xia, Ying-Jie; Wei, Zhang; Xiong, Zikai; Jones, Sian; He, Yiping; Yan, Hai; Wang, Xiaoyue

2015-12-01

Besides CDH1, few hereditary gastric cancer predisposition genes have been previously reported. In this study, we discovered two germline ATM mutations (p.Y1203fs and p.N1223S) in a Chinese family with a history of gastric cancer by screening 83 cancer susceptibility genes. Using a published exome sequencing dataset, we found deleterious germline mutations of ATM in 2.7% of 335 gastric cancer patients of different ethnic origins. The frequency of deleterious ATM mutations in gastric cancer patients is significantly higher than that in general population (p=0.0000435), suggesting an association of ATM mutations with gastric cancer predisposition. We also observed biallelic inactivation of ATM in tumors of two gastric cancer patients. Further evaluation of ATM mutations in hereditary gastric cancer will facilitate genetic testing and risk assessment.

The management of gastric volvulus in elderly patients.

PubMed

Zuiki, Toru; Hosoya, Yoshinori; Lefor, Alan Kawarai; Tanaka, Hiroyuki; Komatsubara, Toshihide; Miyahara, Yuzo; Sanada, Yukihiro; Ohki, Jun; Sekiguchi, Chuji; Sata, Naohiro

2016-01-01

Gastric volvulus is torsion of the stomach and requires immediate treatment. The optimal treatment strategy for patients with gastric volvulus is not established, because of significant variations in the cause and clinical course of this condition. We describe our experience with six elderly patients with gastric volvulus caused by different conditions using various approaches. This includes two patients managed with endoscopic reduction, followed by endoscopic or laparoscopic gastropexy. Endoscopy is a necessary first step to determine the optimal treatment strategy, and endoscopic reduction is often effective. The indications for surgical repair of gastric volvulus depend on the patient's overall condition, and several options are available. In some elderly patients with severe comorbidities, major surgery may have an unacceptably high risk. We propose a novel treatment strategy for gastric volvulus in the elderly and a review of the literature. Early endoscopy is necessary in patients with gastric volvulus. Endoscopic or laparoscopic gastropexy may be adequate therapy in selected elderly patients. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Changing strategies for target therapy in gastric cancer.

PubMed

Lee, Suk-Young; Oh, Sang Cheul

2016-01-21

In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer.

Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

PubMed

Figueiredo, Ceu; Camargo, M C; Leite, Marina; Fuentes-Pananá, Ezequiel M; Rabkin, Charles S; Machado, José C

Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

Gastric Electrical Stimulation

PubMed Central

2006-01-01

Executive Summary Objective The objective of this analysis was to assess the effectiveness, safety and cost-effectiveness of gastric electrical stimulation (GES) for the treatment of chronic, symptomatic refractory gastroparesis and morbid obesity. Background Gastroparesis - Epidemiology Gastroparesis (GP) broadly refers to impaired gastric emptying in the absence of obstruction. Clinically, this can range from the incidental detection of delayed gastric emptying in an asymptomatic person to patients with severe nausea, vomiting and malnutrition. Symptoms of GP are nonspecific and may mimic structural disorders such as ulcer disease, partial gastric or small bowel obstruction, gastric cancer, and pancreaticobiliary disorders. Gastroparesis may occur in association with diabetes, gastric surgery (consequence of peptic ulcer surgery and vagotomy) or for unknown reasons (idiopathic gastroparesis). Symptoms include early satiety, nausea, vomiting, abdominal pain and weight loss. The majority of patients with GP are women. The relationship between upper gastrointestinal symptoms and the rate of gastric emptying is considered to be weak. Some patients with markedly delayed gastric emptying are asymptomatic and sometimes, severe symptoms may remit spontaneously. Idiopathic GP may represent the most common form of GP. In one tertiary referral retrospective series, the etiologies in 146 GP patients were 36% idiopathic, 29% diabetic, 13% postgastric surgery, 7.5% Parkinson’s disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudoobstruction and 6% miscellaneous causes. The true prevalence of digestive symptoms in patients with diabetes and the relationship of these symptoms to delayed gastric emptying are unknown. Delayed gastric emptying is present in 27% to 58% of patients with type 1 diabetes and 30% with type 2 diabetes. However, highly variable rates of gastric emptying have been reported in type 1 and 2 diabetes, suggesting that development of GP in

Gastric volvulus in guinea pigs: comparison with other species.

PubMed

Dudley, Emily S; Boivin, Gregory P

2011-07-01

Gastric volvulus has been documented in several species of animals and is associated with high morbidity and mortality. We report 2 cases of gastric volvulus in guinea pigs that died without detection of prior clinical signs. Both guinea pigs were adult female guinea pigs in a breeding colony and had given birth to multiple litters; one was pregnant at the time of death. Gastric rotations of 540° and 360° were identified at necropsy examination. These cases include the first known report of gastric rotation greater than 360° in any species. Although gastric volvulus has been reported to occur in guinea pigs, little is known about its risk factors, etiology, and pathogenesis. We conducted a literature review to compare gastric volvulus between guinea pigs and other species. Copyright 2011 by the American Association for Laboratory Animal Science

Helicobacter pylori virulence factors in development of gastric carcinoma.

PubMed

Wang, Ming-Yi; Liu, Xiao-Fei; Gao, Xiao-Zhong

2015-01-01

Helicobacter pylori plays a vital role in the pathogenesis of gastric carcinoma. However, only a relatively small proportion of individuals infected with H. pylori develop gastric carcinoma. Differences in the incidence of gastric carcinoma among infected individuals can be explained, at least partly, by the different genotypes of H. pylori virulence factors. Thus far, many virulence factors of H. pylori, such as Cag PAI, VacA, OMPs and DupA, have been reported to be involved in the development of gastric cancer. The risk of developing gastric cancer during H. pylori infection is affected by specific host-microbe interactions that are independent of H. pylori virulence factors. In this review, we discuss virulence factors of H. pylori and their role in the development of gastric carcinoma that will provide further understanding of the biological interactions of H. pylori with the host.

Effect of colectomy on gastric emptying in idiopathic slow-transit constipation.

PubMed

Hemingway, D M; Finlay, I G

2000-09-01

Gastric emptying is delayed in patients with idiopathic slow-transit constipation (ISTC). Gastric emptying was measured before and after colectomy and ileorectal anastomosis in patients with ISTC to determine whether the abnormality persists after operation. Twelve patients undergoing colectomy for severe ISTC had solid-phase gastric emptying measured after an overnight fast. All 12 had an uncomplicated subtotal colectomy and ileorectal anastomosis; 11 had an excellent functional outcome. In ten of these patients gastric emptying was repeated within 3 months of operation. Seven patients (including the remaining two) had the study performed at 1 year. All 12 patients had severely delayed gastric emptying before operation. Gastric emptying remained delayed in the ten patients who underwent an early postoperative gastric emptying study. Six of seven patients assessed at 1 year had improved gastric emptying, of whom four had returned to normal. Functional outcome did not relate to gastric emptying. Patients with ISTC have delayed gastric emptying. In some patients this returns to normal after colectomy, but is persistent in others. This may have implications for our understanding of ISTC.

Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers

PubMed Central

Garcia-Bloj, Benjamin; Fry, Jacqueline; Wichmann, Ignacio

2015-01-01

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade. PMID:26379360

Epstein-Barr Virus (EBV)-associated Gastric Carcinoma

PubMed Central

Iizasa, Hisashi; Nanbo, Asuka; Nishikawa, Jun; Jinushi, Masahisa; Yoshiyama, Hironori

2012-01-01

The ubiquitous Epstein-Barr virus (EBV) is associated with several human tumors, which include lymphoid and epithelial malignancies. It is known that EBV persistently infects the memory B cell pool of healthy individuals by activating growth and survival signaling pathways that can contribute to B cell lymphomagenesis. Although the monoclonal proliferation of EBV-infected cells can be observed in epithelial tumors, such as nasopharyngeal carcinoma and EBV-associated gastric carcinoma, the precise role of EBV in the carcinogenic progress is not fully understood. This review features characteristics and current understanding of EBV-associated gastric carcinoma. EBV-associated gastric carcinoma comprises almost 10% of all gastric carcinoma cases and expresses restricted EBV latent genes (Latency I). Firstly, definition, epidemiology, and clinical features are discussed. Then, the route of infection and carcinogenic role of viral genes are presented. Of particular interest, the association with frequent genomic CpG methylation and role of miRNA for carcinogenesis are topically discussed. Finally, the possibility of therapies targeting EBV-associated gastric carcinoma is proposed. PMID:23342366

Efficient removal of caesium ions from aqueous solution using a calix crown ether in ionic liquids: mechanism and radiation effect.

PubMed

Xu, Chao; Yuan, Liyong; Shen, Xinghai; Zhai, Maolin

2010-04-28

The removal of radioactive (137)Cs from nuclear waste is of great importance for both the environment and energy saving. Herein, we report a study on the removal of Cs(+) using a calix crown ether bis(2-propyloxy)calix[4]crown-6 (BPC6) in ionic liquids [C(n)mim][NTf(2)], where [C(n)mim](+) is 1-alkyl-3-methylimidazolium and [NTf(2)](-) is bis(trifluoromethylsulfonyl)imide. The BPC6/[C(n)mim][NTf(2)] system is highly efficient in removing Cs(+) from aqueous solution, even at a low concentration of BPC6. HNO(3) and metal ions such as Na(+), Al(3+) in the aqueous phase interfered with the extraction of Cs(+) by competitive interaction with BPC6 and/or salting-out effect. UV analysis confirmed that the extraction of Cs(+) by the BPC6/[C(n)mim][NTf(2)] system involves a dual extraction mechanism, i.e., via exchange of BPC6.Cs(+) complex or Cs(+) by [C(n)mim](+). Irradiation of [C(4)mim][NTf(2)] dramatically decreases Cs(+) partitioning in the ionic liquid phase by the competitive interaction of radiation-generated H(+) with BPC6, while irradiation of BPC6/[C(4)mim][NTf(2)] decreases Cs(+) partitioning more markedly due to the radiolysis of BPC6.

Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota

PubMed Central

Pereira-Marques, Joana; Pinto-Ribeiro, Ines; Costa, Jose L; Carneiro, Fatima; Machado, Jose C

2018-01-01

Objective Gastric carcinoma development is triggered by Helicobacter pylori. Chronic H. pylori infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial community. This change in the microbiome may increase aggression to the gastric mucosa and contribute to malignancy. Our aim was to evaluate the composition of the gastric microbiota in chronic gastritis and in gastric carcinoma. Design The gastric microbiota was retrospectively investigated in 54 patients with gastric carcinoma and 81 patients with chronic gastritis by 16S rRNA gene profiling, using next-generation sequencing. Differences in microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Associations between the most relevant taxa and clinical diagnosis were validated by real-time quantitative PCR. Predictive functional profiling of microbial communities was obtained with PICRUSt. Results The gastric carcinoma microbiota was characterised by reduced microbial diversity, by decreased abundance of Helicobacter and by the enrichment of other bacterial genera, mostly represented by intestinal commensals. The combination of these taxa into a microbial dysbiosis index revealed that dysbiosis has excellent capacity to discriminate between gastritis and gastric carcinoma. Analysis of the functional features of the microbiota was compatible with the presence of a nitrosating microbial community in carcinoma. The major observations were confirmed in validation cohorts from different geographic origins. Conclusions Detailed analysis of the gastric microbiota revealed for the first time that patients with gastric carcinoma exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of patients with chronic gastritis. PMID:29102920

Robot-assisted laparoscopic gastrectomy for gastric cancer

PubMed Central

Caruso, Stefano; Franceschini, Franco; Patriti, Alberto; Roviello, Franco; Annecchiarico, Mario; Ceccarelli, Graziano; Coratti, Andrea

2017-01-01

Phase III evidence in the shape of a series of randomized controlled trials and meta-analyses has shown that laparoscopic gastrectomy is safe and gives better short-term results with respect to the traditional open technique for early-stage gastric cancer. In fact, in the East laparoscopic gastrectomy has become routine for early-stage gastric cancer. In contrast, the treatment of advanced gastric cancer through a minimally invasive way is still a debated issue, mostly due to worries about its oncological efficacy and the difficulty of carrying out an extended lymphadenectomy and intestinal reconstruction after total gastrectomy laparoscopically. Over the last ten years the introduction of robotic surgery has implied overcoming some intrinsic drawbacks found to be present in the conventional laparoscopic procedure. Robot-assisted gastrectomy with D2 lymphadenectomy has been shown to be safe and feasible for the treatment of gastric cancer patients. But unfortunately, most available studies investigating the robotic gastrectomy for gastric cancer compared to laparoscopic and open technique are so far retrospective and there have not been phase III trials. In the present review we looked at scientific evidence available today regarding the new high-tech surgical robotic approach, and we attempted to bring to light the real advantages of robot-assisted gastrectomy compared to the traditional laparoscopic and open technique for the treatment of gastric cancer. PMID:28101302

Cytoplasmic Drosha Is Aberrant in Precancerous Lesions of Gastric Carcinoma and Its Loss Predicts Worse Outcome for Gastric Cancer Patients.

PubMed

Zhang, Hailong; Hou, Yixuan; Xu, Liyun; Zeng, Zongyue; Wen, Siyang; Du, Yan-E; Sun, Kexin; Yin, Jiali; Lang, Lei; Tang, Xiaoli; Liu, Manran

2016-04-01

The nuclear localization of Drosha is critical for its function as a microRNA maturation regulator. Dephosphorylation of Drosha at serine 300 and serine 302 disrupts its nuclear localization, and aberrant distribution of Drosha has been detected in some tumors. The purpose of the present study was to assess cytoplasmic/nuclear Drosha expression in gastric cancer carcinogenesis and progression. Drosha expression and its subcellular location was investigated by immunohistochemical staining of a set of tissue microarrays composed of normal adjacent tissues (374), chronic gastritis (137), precancerous lesions (94), and gastric adenocarcinoma (829) samples, and in gastric cancer cell lines with varying differentiation by immunofluorescence and western blot assay. Gradual loss of cytoplasmic Drosha was accompanied by tumor progression in both gastric cancer tissues and cell lines, and was inversely associated with tumor volume (P = 0.002), tumor grade (P < 0.001), tumor stage (P = 0.018), and distant metastasis (P = 0.026). Aberrant high levels of cytoplasmic Drosha were apparent in intestinal metaplasia and dysplasia tissues. The levels of nuclear Drosha were sharply decreased in chronic gastritis and maintained through precancerous lesions to gastric cancer. High levels of cytoplasmic Drosha predicted longer survival (LR = 7.088, P = 0.008) in gastric cancer patients. Our data provide novel insights into gastric cancer that cytoplasmic Drosha potentially plays a role in preventing carcinogenesis and tumor progression, and may be an independent predictor of patient outcome.

Roux-en-Y gastric bypass operation in rats.

PubMed

Bueter, Marco; Abegg, Kathrin; Seyfried, Florian; Lutz, Thomas A; le Roux, Carel W

2012-06-11

Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality benefit is bariatric surgery. Consequently, there has been a steady rise in the number of bariatric operations done worldwide in recent years with the Roux-en-Y gastric bypass (gastric bypass) being the most commonly performed operation. Against this background, it is important to understand the physiological mechanisms by which gastric bypass induces and maintains body weight loss. These mechanisms are yet not fully understood, but may include reduced hunger and increased satiation, increased energy expenditure, altered preference for food high in fat and sugar, altered salt and water handling of the kidney as well as alterations in gut microbiota. Such changes seen after gastric bypass may at least partly stem from how the surgery alters the hormonal milieu because gastric bypass increases the postprandial release of peptide-YY (PYY) and glucagon-like-peptide-1 (GLP-1), hormones that are released by the gut in the presence of nutrients and that reduce eating. During the last two decades numerous studies using rats have been carried out to further investigate physiological changes after gastric bypass. The gastric bypass rat model has proven to be a valuable experimental tool not least as it closely mimics the time profile and magnitude of human weight loss, but also allows researchers to control and manipulate critical anatomic and physiologic factors including the use of appropriate controls. Consequently, there is a wide array of rat gastric bypass models available in the literature reviewed elsewhere in more detail. The description of the exact surgical technique of these models varies widely and differs e.g. in terms of pouch size, limb lengths, and the preservation of the vagal nerve. If reported, mortality rates seem to range from 0 to 35%. Furthermore, surgery has been carried out almost exclusively in male

Effects of legumain as a potential prognostic factor on gastric cancers.

PubMed

Li, Na; Liu, Qiaoling; Su, Qi; Wei, Chongyang; Lan, Bin; Wang, Jianyong; Bao, Guoqing; Yan, Fei; Yu, Ying; Peng, Baowei; Qiu, Ju; Yan, Xiangming; Zhang, Sheng; Guo, Fang

2013-01-01

Although legumain has been found to be a prognostic factor in both breast cancer and colorectal cancer, its effects on gastric cancer are unknown. In this study, we investigated effects of legumain on gastric cancer and the correlation between legumain expression and prognosis of gastric cancer patients. SGC7901 cells were transduced with legumain cDNA (SGC7901-hLeg) for overexpression of legumain or with legumain shRNA to knock down legumain. In vitro tumor migration was examined by wound healing assay. Furthermore, a tumorigenicity and metastasis mouse model was used to examine legumain function in vivo; asparaginyl endopeptidase inhibitor (AEPI, an inhibitor of legumain) was injected to the mice (i.p.) to evaluate its therapeutic effect. Tissue microarray analysis from 112 gastric cancer patients was performed to evaluate the association between legumain expression and the cumulative survival time. Legumain was highly expressed in gastric cancer patients and some gastric cancer cell lines. Legumain promoted gastric cell migration in vitro and promoted gastric tumor growth and metastasis in vivo, and these effects were reversed by knockdown of legumain with shRNA or treated with AEPI. In gastric cancer clinical samples, legumain expression in tumor was significantly higher than in non-tumor and was negatively associated with the cumulative survival rate. In conclusion, legumain was highly expressed in gastric adenocarcinoma; legumain promoted gastric cancer tumorigenesis and metastasis in vitro and in vivo. Legumain expression in tumor was a poor prognostic factor for gastric cancer patients, and legumain could be a potential target molecule for gastric cancer therapy in clinic.

Impact of endoscopic screening on mortality reduction from gastric cancer

PubMed Central

Hamashima, Chisato; Ogoshi, Kazuei; Narisawa, Rintarou; Kishi, Tomoki; Kato, Toshiyuki; Fujita, Kazutaka; Sano, Masatoshi; Tsukioka, Satoshi

2015-01-01

AIM: To investigate mortality reduction from gastric cancer based on the results of endoscopic screening. METHODS: The study population consisted of participants of gastric cancer screening by endoscopy, regular radiography, and photofluorography at Niigata city in 2005. The observed numbers of cumulative deaths from gastric cancers and other cancers were accumulated by linkage with the Niigata Prefectural Cancer Registry. The standardized mortality ratio (SMR) of gastric cancer and other cancer deaths in each screening group was calculated by applying the mortality rate of the reference population. RESULTS: Based on the results calculated from the mortality rate of the population of Niigata city, the SMRs of gastric cancer death were 0.43 (95%CI: 0.30-0.57) for the endoscopic screening group, 0.68 (95%CI: 0.55-0.79) for the regular radiographic screening group, and 0.85 (95%CI: 0.71-0.94) for the photofluorography screening group. The mortality reduction from gastric cancer was higher in the endoscopic screening group than in the regular radiographic screening group despite the nearly equal mortality rates of all cancers except gastric cancer. CONCLUSION: The 57% mortality reduction from gastric cancer might indicate the effectiveness of endoscopic screening for gastric cancer. Further studies and prudent interpretation of results are needed. PMID:25741155

Diagnosis and Management of High Risk Group for Gastric Cancer

PubMed Central

Yoon, Hyuk; Kim, Nayoung

2015-01-01

Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086

Chronic gastric instability and presumed incomplete volvulus in dogs.

PubMed

Paris, J K; Yool, D A; Reed, N; Ridyard, A E; Chandler, M L; Simpson, J W

2011-12-01

Chronic gastric volvulus in dogs results in long-standing gastrointestinal signs unlike those of acute gastric dilatation and volvulus. This report describes chronic gastric volvulus in seven dogs. The majority of dogs presented with weight loss, chronic vomiting, lethargy and abdominal pain. A combination of radiographic, ultrasonographic and endoscopic imaging indicated altered positioning of gastric landmarks. Dynamic changes were identified in some cases. Exploratory coeliotomy and surgical gastropexy were performed in all dogs. Clinical signs improved or resolved in six of seven dogs postoperatively. Chronic gastric volvulus is an uncommon condition in dogs, but should be considered as a differential in cases presenting with the above clinical signs. © 2011 British Small Animal Veterinary Association.

Identifying module biomarkers from gastric cancer by differential correlation network

PubMed Central

Liu, Xiaoping; Chang, Xiao

2016-01-01

Gastric cancer (stomach cancer) is a severe disease caused by dysregulation of many functionally correlated genes or pathways instead of the mutation of individual genes. Systematic identification of gastric cancer biomarkers can provide insights into the mechanisms underlying this deadly disease and help in the development of new drugs. In this paper, we present a novel network-based approach to predict module biomarkers of gastric cancer that can effectively distinguish the disease from normal samples. Specifically, by assuming that gastric cancer has mainly resulted from dysfunction of biomolecular networks rather than individual genes in an organism, the genes in the module biomarkers are potentially related to gastric cancer. Finally, we identified a module biomarker with 27 genes, and by comparing the module biomarker with known gastric cancer biomarkers, we found that our module biomarker exhibited a greater ability to diagnose the samples with gastric cancer. PMID:27703371

Stomach (Gastric) Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

For stomach (gastric) cancer, there is no standard or routine screening test for the general U.S. population. Review the evidence on the benefits and harms of screening for gastric cancer using barium-meal photofluorography, gastric endoscopy, or serum pepsinogen in this expert-reviewed summary.

Insights into next developments in advanced gastric cancer.

PubMed

Obermannová, Radka; Lordick, Florian

2016-07-01

The purpose of the review is to delineate novel approaches for biology-based treatment in advanced gastric cancer. We reviewed the latest translational and clinical research articles and congress presentations. A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification. Anti-HER2 treatment, which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting. However, resistance mechanisms in advanced disease are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is an emerging concept in the management of advanced gastric cancer, and ramucirumab has prolonged survival in the second line either as a monotherapy or in combination with paclitaxel. Biomarkers for selecting patients who benefit from ramucirumab are still lacking. Immune checkpoint blockade and inhibition of cancer stemness targets are other emerging directions for the medical treatment of gastric cancer. Large-scale international studies are ongoing. Promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment strategies.

Advances of Molecular Targeted Therapy in Gastric Cancer.

PubMed

Cetin, Bulent; Gumusay, Ozge; Cengiz, Mustafa; Ozet, Ahmet

2016-06-01

Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life. In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats-Correlation of HSP72 expression with mucosal protection

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

Wada, Isao; Otaka, Michiro; Jin, Mario

2006-10-20

Background and aim: The real mechanism of adaptive cytoprotection in the gastric mucosa is not well established. In the present study, we investigated the effect of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression, which is known as endogenous cytoprotective factor, in the gastric mucosa. Also, the association of gastric mucosal protective function against HCl-challenge was compared between HSP72-induced and -reduced group. Materials and methods: Expression of HSP72 was measured by Western blotting in the gastric mucosa before and after administration of famotidine or omeprazole. The gastric mucosal protective function against 0.6 N HCl was compared betweenmore » control group and HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by additional administration of zinc sulfate or zinc L-carnosine, which is known as HSP72-inducer, on mucosal protective function was studied. Results: HSP72 expression in the gastric mucosa was reduced by acid suppressing agents. The lowest expression level of HSP72 was observed 12 h (famotidine, H2-receptor antagonist) or 48 h (omeprazole, proton pump inhibitor) after administration. The gastric mucosal protective ability against 0.6 N HCl was also reduced when HSP72 expression was decreased by famotidine or omeprazole. This phenomenon was reversed by HSP72 induction by additional administration of zinc derivatives. Conclusion: Our results might indicate that the expression of HSP72 in the gastric mucosa is physiologically regulated by gastric acid, and that HSP72 induction could be important in view of mucosal protection especially when HSP72 expression is reduced by administration of acid suppressing agents such as proton pump inhibitor or H2 receptor antagonist.« less

Accelerated Gastric Emptying but No Carbohydrate Malabsorption 1 Year After Gastric Bypass Surgery (GBP)

PubMed Central

Wang, Gary; Agenor, Keesandra; Pizot, Justine; Kotler, Donald P.; Harel, Yaniv; Van Der Schueren, Bart J.; Quercia, Iliana; McGinty, James

2013-01-01

Background Following gastric bypass surgery (GBP), there is a post-prandial rise of incretin and satiety gut peptides. The mechanisms of enhanced incretin release in response to nutrients after GBP is not elucidated and may be in relation to altered nutrient transit time and/or malabsorption. Methods Seven morbidly obese subjects (BMI=44.5±2.8 kg/m2) were studied before and 1 year after GBP with a d-xylose test. After ingestion of 25 g of d-xylose in 200 mL of non-carbonated water, blood samples were collected at frequent time intervals to determine gastric emptying (time to appearance of d-xylose) and carbohydrate absorption using standard criteria. Results One year after GBP, subjects lost 45.0±9.7 kg and had a BMI of 27.1±4.7 kg/m2. Gastric emptying was more rapid after GBP. The mean time to appearance of d-xylose in serum decreased from 18.6±6.9 min prior to GBP to 7.9±2.7 min after GBP (p=0.006). There was no significant difference in absorption before (serum d-xylose concentrations=35.6±12.6 mg/dL at 60 min and 33.9±9.1 mg/dL at 180 min) or 1 year after GBP (serum d-xylose=31.5± 18.1 mg/dL at 60 min and 27.2±11.9 mg/dL at 180 min). Conclusions These data confirm the acceleration of gastric emptying for liquid and the absence of carbohydrate malabsorption 1 year after GBP. Rapid gastric emptying may play a role in incretin response after GBP and the resulting improved glucose homeostasis. PMID:22527599

[Effects of preoperative oral carbohydrate administration on gastric contents].

PubMed

Sato, Chiaki; Shibuya, Hiromi; Nishino, Miho; Maeda, Akihiko; Shimakawa, Noriko; Okada, Toshiki

2012-08-01

Preoperative oral carbohydrate administration for adult patients has been recommended by European Society for Parenteral and Enteral Nutrition and Enhanced Recovery After Surgery. Although preoperative oral carbohydrate may improve patient satisfaction and perioperative glucose metabolism, its effects on the gastric contents remain controversial. We included 232 adult patients without gastrointestinal stenosis or occlusion. Seventy-four patients (group A) were not permitted to eat or drink before operation for eight hours, while 158 patients (group B) took oral carbohydrate (225 ml, 22.3% glucose) two hours before anesthesia induction. After induction, gastric contents were aspirated to examine its volume and pH. Although the mean volume of gastric contents of the patients in group B was significantly lower than that in group A, and gastric pH was also significantly smaller in group B, no patients suffered from aspiration during rapid induction. Fasting interval and gastric volume were inversely related, and almost all the patients with fasting interval above 150 minutes showed gastric contents volume smaller than 25 ml and gastric pH more than 2.5. We conclude that preoperative oral carbohydrate can be given safely, although the fasting interval should be 150 minutes in our diet regimen.

Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines

PubMed Central

Calcagno, Danielle Queiroz; Takeno, Sylvia Santomi; Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Wisnieski, Fernanda; Chen, Elizabeth Suchi; Araújo, Taíssa Maíra Thomaz; Lima, Eleonidas Moura; Melaragno, Maria Isabel; Demachki, Samia; Assumpção, Paulo Pimentel; Burbano, Rommel Rodriguez; Smith, Marília Cardoso

2016-01-01

AIM To identify common copy number alterations on gastric cancer cell lines. METHODS Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis. RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha (IL11RA) and maternal embryonic leucine zipper kinase (MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11RA and MELK was observed in 19.1% (13/68) and 55.9% (38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer. PMID:27920471

Influence of experimental hypokinesia on gastric secretory function

NASA Technical Reports Server (NTRS)

Markova, O. O.; Vavryshchuk, V. I.; Rozvodovskyy, V. I.; Proshcheruk, V. A.

1980-01-01

The gastric secretory function of rats was studied in 4, 8, 16 and 30 day hypokinesia. Inhibition of both the gastric juice secretory and acid producing functions was found. The greatest inhibition was observed on day 8 of limited mobility. By days 16 and 30 of the experiment, a tendency of the gastric secretory activity to return to normal was observed, although it remained reduced.

[Interleukin-10-1082 promoter polymorphism and the risk of gastric cancer].

PubMed

Yin, Yi-qiong; Liu, Chun-juan; Zhang, Ming-ming; Zhou, Yong

2012-05-01

To investigate the association between Interleukin-10 (IL-10) promoter polymorphism and the gastric cancer risk in Chinese Han patients. DNA was extracted from blood samples of gastric cancer patients (n = 75) and controls (n = 75). IL-10 -1082 promoter polymorphism in both patient and control group (three genotypes distribution: AA, AG and GG) was identified by PCR-RFLP and its relationship with gastric cancer risk, clinic and pathologic features was also analyzed. Patients with gastric cancer had a significantly lower frequency of AA (OR = 0.43, 95% CI = 0.20, 0.92; P = 0.03) than controls. Patients with proximal gastric cancer had a significantly higher frequency of GG (OR = 3.06, 95% CI = 1.12, 8.36; P = 0.03) than those with distant gastric cancer. Patients with advanced (stage II/IV) gastric cancer had a significantly higher frequency of AA (OR = 5.09, 95% CI = 1.05, 24.70; P = 0.04) than those with early (stage I /IV) gastric cancer. When stratified by the Lauren's classification, histological differentiation of gastric cancer, no statistically significant results was observed. This study suggests that the IL-1 1082 promoter polymorphism may be associated with gastric cancer in Chinese Han patients, and the difference in genotype distribution may be associated with the location and stage of gastric cancer.

Postprandial inhibition of gastric ghrelin secretion by long-chain fatty acid through GPR120 in isolated gastric ghrelin cells and mice

PubMed Central

Lu, Xinping; Zhao, Xilin; Feng, Jianying; Liou, Alice P.; Anthony, Shari; Pechhold, Susanne; Sun, Yuxiang; Lu, Huiyan

2012-01-01

Ghrelin is a gastric peptide hormone that controls appetite and energy homeostasis. Plasma ghrelin levels rise before a meal and fall quickly thereafter. Elucidation of the regulation of ghrelin secretion has been hampered by the difficulty of directly interrogating ghrelin cells diffusely scattered within the complex gastric mucosa. Therefore, we generated transgenic mice with ghrelin cell expression of green fluorescent protein (GFP) to enable characterization of ghrelin secretion in a pure population of isolated gastric ghrelin-expressing GFP (Ghr-GFP) cells. Using quantitative RT-PCR and immunofluorescence staining, we detected a high level of expression of the long-chain fatty acid (LCFA) receptor GPR120, while the other LCFA receptor, GPR40, was undetectable. In short-term-cultured pure Ghr-GFP cells, the LCFAs docosadienoic acid, linolenic acid, and palmitoleic acid significantly suppressed ghrelin secretion. The physiological mechanism of LCFA inhibition on ghrelin secretion was studied in mice. Serum ghrelin levels were transiently suppressed after gastric gavage of LCFA-rich lipid in mice with pylorus ligation, indicating that the ghrelin cell may directly sense increased gastric LCFA derived from ingested intraluminal lipids. Meal-induced increase in gastric mucosal LCFA was assessed by measuring the transcripts of markers for tissue uptake of LCFA, lipoprotein lipase (LPL), fatty acid translocase (CD36), glycosylphosphatidylinositol-anchored HDL-binding protein 1, and nuclear fatty acid receptor peroxisome proliferator-activated receptor-γ. Quantitative RT-PCR studies indicate significantly increased mRNA levels of lipoprotein lipase, glycosylphosphatidylinositol-anchored HDL-binding protein 1, and peroxisome proliferator-activated receptor-γ in postprandial gastric mucosa. These results suggest that meal-related increases in gastric mucosal LCFA interact with GPR120 on ghrelin cells to inhibit ghrelin secretion. PMID:22678998

Laparoscopic gastric plication: technical report.

PubMed

El-Geidie, Ahmed; Gad-el-Hak, Nabil

2014-01-01

Laparoscopic gastric plication is an emerging restrictive bariatric procedure but still lacks standardization of the technique. The aim of this study was to apply a standardized, modified 3-port approach to laparoscopic gastric plication to improve outcomes. The modified laparoscopic gastric plication technique was applied for 63 morbidly obese patients between March 2010 and January 2013. There were 9 men and 54 women, with a mean age of 34.2 years (range 20-48 years) and a mean body mass index of 38.9 kg/m(2) (range 32-65 kg/m(2)). There were no deaths, no conversion to laparotomy, no reoperation, and no readmission. Percent excess weight loss was 41%, 52%, and 60% at 3, 6, and 12 months, respectively. There were no major complications reported in our study, but prolonged early postoperative nausea and vomiting occurred in 3 of 63 (4.8%) patients who had been successfully treated with proton pump inhibitors and antiemetics. Our initial experience showed that the 4-bite technique starting 2 cm below the angle of His with tight calibration of the gastric tube for obese patients is feasible, effective, and well tolerated, with a low frequency of major problems. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Exfoliation of gastric pit-parietal cells into the gastric lumen associated with a stimulation of isolated rat gastric mucosa in vitro: a morphological study by the application of cryotechniques.

PubMed

Aoyama, Fumiyo; Sawaguchi, Akira; Ide, Soyuki; Kitamura, Kazuo; Suganuma, Tatsuo

2008-06-01

It is clinicopathologically important to elucidate the cell kinetics for the maintenance of normal gastric epithelium. In a rat gastric mucosa isolated after stimulation, a number of cells were exfoliated into the gastric lumen of the pit region. The present study was undertaken to clarify the origin of exfoliated cells and their histochemical profiles by taking the advantages of cryotechniques. As results, most of the exfoliated cells were identified as pit-parietal cells labeled with both peanut-lectin and anti-H+/K+-ATPase antibody. Quantitative analysis verified a time-dependent increase in the number of exfoliated cells in the gastric mucosa isolated after stimulation. The exfoliated cells exhibited a diffuse intracellular staining for E-cadherin, suggesting a dissociation of the adhesion molecule prior to the cell exfoliation. It should be noted that most of the exfoliated cells were negative to the apoptotic markers (TUNEL staining and caspase-3). Ultrastructurally, autophagosome-like structures consisting of H+/K+-ATPase positive membranes were frequently seen in the exfoliated pit-parietal cells. In addition, the pit-parietal cell exfoliation was accompanied by sealing of their basal portion with the cytoplasmic processes of adjacent surface mucous cells. The present morphological findings provide a new insight into the cell kinetics in the gastric epithelium in vitro.