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1.
Clin J Gastroenterol ; 16(6): 854-858, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37733231

RESUMO

The metastasis of breast cancer to the gastrointestinal tract is rare. Herein, we presented the case of an 85-year-old woman who had a history of invasive lobular carcinoma and experienced complete colon rupture due to relatively low-energy trauma. The patient underwent bilateral total mastectomy and axillary dissection following preoperative chemotherapy 6 years ago. She had a local recurrence 2 years after the surgery and underwent chemotherapy. Subsequently, the cancer metastasized to the thoracolumbar area and retroperitoneum. In addition, the patient fell from a height of 30 cm while hanging laundry and her abdomen hit a hose reel. Emergency surgery was performed, and the entire circumference of the sigmoid colon was ruptured. The ruptured colon lesion was resected, and the stump was closed. A double-barrel transverse colostomy was created as it was impossible to lift the stump up to the abdominal wall. Histopathological examination revealed the invasive lobular carcinoma metastasis and a linitis plastica-like change of the colon wall, which probably consequently weakened. In addition, minimal trauma can damage the gastrointestinal tract that had invasive lobular carcinoma metastasis.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Segunda Neoplasia Primária , Feminino , Humanos , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Lobular/secundário , Colo Sigmoide/patologia , Mastectomia , Segunda Neoplasia Primária/cirurgia , Melanoma Maligno Cutâneo
2.
Surg Case Rep ; 6(1): 186, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737607

RESUMO

BACKGROUND: Malignant peripheral nerve sheath tumour (MPNST) is a very rare disease, and its pathogenesis is unknown. There are few reports of MPNST of the oesophagus. We report a case of an MPNST that was diagnosed and resected. CASE PRESENTATION: A 30-year-old female presented with dysphagia. She had been aware of the dysphagia approximately 6 months before presentation. The chest X-ray showed shadows in the right mediastinum. Barium fluoroscopy revealed a semicircular raised lesion in the lower oesophagus. Upper gastrointestinal endoscopy revealed a type 1 oesophageal tumour centred on the posterior wall 26-35 cm from the incisors. The surface was ulcerated, and the tumour was exposed. The affected area showed no iodine uptake. The EUS showed an isoechoic mass. The CT scan showed a mass of 71 × 61 × 55 mm in the beginning of the lower oesophagus with low density mass and swelling of the right recurrent nerve lymph node to 12 mm. On FDG-PET, the tumour showed an SUVmax of 11.05, and no abnormal accumulation was found in lymph nodes or other organs. The MRI showed a hyperintense mass on the T2WI, which had prolonged contrast enhancement, and no findings of invasion into surrounding tissue were found. The patient underwent right thoracotomy and open thoracic oesophagectomy. The affected lymph node was tumour negative by rapid pathological diagnosis during the operation. Histologically, spindle cells with different-sized nuclei were mixed throughout the tissue. Some regions showed nuclear polymorphism or a storiform pattern, and locally, there were approximately 7 mitoses/10 HPFs. The margin was relatively clear, but spindle-shaped tumour cells infiltrated the surrounding interstitium and basal myoepithelium, and the patient was diagnosed with MPNST. In this case, the postoperative course was good, and 16 months after the operation, the patient is currently under observation at the outpatient stage without recurrence. CONCLUSIONS: MPNST in the oesophagus is a relatively rare disease. Diagnosis before treatment is sometimes difficult, but the prognosis is good if radical resection is possible.

3.
Surg Oncol ; 29: 97-101, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31196501

RESUMO

PURPOSES: Oral mucositis is one of the most common reasons for discontinuation of S-1 adjuvant chemotherapy after radical gastrectomy. Some studies suggest that nutritional support with amino acids may improve oral mucositis. We conducted a prospective, randomized clinical trial of patients who underwent adjuvant chemotherapy for gastric cancer to examine whether an oral elemental diet prevents chemotherapy associated oral mucositis and body weight loss. METHODS: Patients were randomly assigned to a group consuming Elental® (the treatment group, n = 11) or a control diet group (n = 11). Patients in the treatment group consumed one pack of Elental® per day during adjuvant chemotherapy. The primary endpoint was the presence and grade of oral mucositis. Secondary endpoints included adherence to Elental® based on the doses recorded in a diary, changes in nutrition parameters, and frequency and severity of adverse events. RESULTS: The incidence of oral mucositis was significantly lower in the treatment group (9.1%) than in the control group (27.3%). The median body weight loss in the treatment group was significantly smaller than that in the control group (P = .015). According to Kaplan-Meier estimates the treatment group was significantly associated with high cumulative S-1 continuation rates (log-rank P = .047). CONCLUSION: We conclude that the amino-acid-rich elemental diet Elental® may be useful as a countermeasure for S-1 adjuvant chemotherapy-induced mucositis.


Assuntos
Adenocarcinoma/tratamento farmacológico , Diarreia/prevenção & controle , Alimentos Formulados , Apoio Nutricional , Ácido Oxônico/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Estomatite/prevenção & controle , Tegafur/efeitos adversos , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Estudos de Casos e Controles , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/patologia , Estomatite/induzido quimicamente , Estomatite/epidemiologia , Adulto Jovem
4.
Digestion ; 97(1): 20-25, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29393163

RESUMO

BACKGROUND: Only limited data are available concerning the long-term outcomes of imatinib treatment among Japanese or Asian patients with advanced or recurrent gastrointestinal stromal tumors (GIST). Our multicenter study, which was conducted in northern Kanto, Japan, aimed to assess the efficacy of imatinib mesylate against advanced or recurrent GIST. SUMMARY: The clinicopathological data of 234 GIST patients who were treated at one of the 11 participating hospitals from 2001 to 2011 were retrospectively reviewed (GREAT study). Imatinib was administered as a first-line therapy in cases involving unresectable disease or postoperative recurrence (41 cases). The patients treated with imatinib (n = 41) exhibited 1-, 3-, and 5-year overall survival (OS) rates of 92.3, 74.9, and 53.8% respectively. In univariate and multivariate analyses, imatinib continuation with dose reduction and achieving a complete or partial response were found to be associated with increased OS. The results of 2 large-scale, long-term trials demonstrate that the risk of tumor progression decreases with increased treatment duration. Furthermore, the interruption of imatinib treatment in responsive and controlled patients results in a high risk of disease progression. Key Messages: Long-term imatinib treatment is recommended for patients with nonprogressive disease. If patients experience significant toxicities, temporary dose reduction and treatment continuation might be useful.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/terapia , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/sangue , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Feminino , Seguimentos , Gastrectomia , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/sangue , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/sangue , Japão/epidemiologia , Assistência de Longa Duração/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Inibidores de Proteínas Quinases/sangue , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
5.
World J Gastroenterol ; 23(42): 7541-7550, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29204054

RESUMO

AIM: To investigate the significance of heat shock protein 110 (HSP110) in gastric cancer (GC) patients with peritoneal metastasis undergoing hyperthermo-chemotherapy. METHODS: Primary GC patients (n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermo-chemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS: HSP110 immnohistochemical staining in 14 GC patients showed that five (35.7%) samples belonged to the low expression group, and nine (64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group (P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis (P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 °C in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 °C, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro. CONCLUSION: The expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Proteínas de Choque Térmico HSP110/metabolismo , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/metabolismo , Antineoplásicos/administração & dosagem , Compostos Benzidrílicos , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Feminino , Proteínas de Choque Térmico HSP110/antagonistas & inibidores , Humanos , Hipertermia Induzida , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/tratamento farmacológico , Peritônio/patologia , Pirrolidinonas , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
6.
Oncol Rep ; 38(3): 1500-1506, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28731175

RESUMO

Heat shock proteins (HSPs), particularly HSP70, help restore normal cellular function following damage caused by stressors. HSP expression in tumor tissues indicates cancer progression, and while the development of HSP inhibitors is progressing, these substances are not widely used to treat cancer. HIKESHI (C11orf73) does not control the intracellular movement of HSP70 at normal temperatures; however, it does regulate the function and movements of HSP70 during heat shock. In this study, we examined the intracellular movement of HSP70 during heat shock to investigate the significance of HIKESHI expression in gastric cancer (GC) and determine if HIKESHI inhibition has cytotoxic effects. We examined HIKESHI using GC cell lines and immunostaining in 207 GC tissue samples. HIKESHI expression in GC tissues was associated with the progression of lymphatic invasion. Suppressing HIKESHI using siRNA did not affect cell viability at normal temperatures. However, suppressing HIKESHI during heat shock inhibited HSP70 nuclear transport and suppressed cell viability. Our results suggest that HIKESHI is a marker of cancer progression and that the combination of HIKESHI inhibition and hyperthermia is a therapeutic tool for refractory GC.


Assuntos
Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica/genética , Resposta ao Choque Térmico/genética , Neoplasias Gástricas/genética , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/genética , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Linhagem Celular Tumoral , Núcleo Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Citotoxinas/administração & dosagem , Citotoxinas/efeitos adversos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
7.
Br J Cancer ; 116(9): 1177-1185, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28334732

RESUMO

BACKGROUND: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases. METHODS: Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples. The roles of STMN1 in cancer cell proliferation and sensitivity to a microtubule-targeting drug, paclitaxel, were confirmed by knockdown experiments using GC cell lines. RESULTS: Multivariate and Kaplan-Meier analyses demonstrated that high STMN1 was predictive of poor prognosis in both the groups. In the operable cohort, STMN1 expression correlated with cancer curability, recurrence, and resistance to adjuvant therapy. A correlation with paclitaxel resistance was observed in inoperable cases. Knockdown of STMN1 in GC cell lines inhibited proliferation and sensitised the cells to paclitaxel by enhancing apoptosis. CONCLUSIONS: STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC.


Assuntos
Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Estatmina/genética , Neoplasias Gástricas/tratamento farmacológico , Idoso , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
8.
Anticancer Res ; 37(1): 191-196, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28011490

RESUMO

BACKGROUND: F-Box protein 45 (FBXO45) is reported to be associated with cancer aggressiveness. We investigated the relationship between FBXO45 and clinicopathological factors in gastric cancer (GC). MATERIALS AND METHODS: We used immunohistochemistry to investigate FBXO45 expression in 104 GC samples; the prognostic value of FBXO45 was also calculated. RESULTS: FBXO45 levels in GC were higher than in normal tissues. Patients with relatively low FBXO45 expression (n=58) had increased cancer progression and poorer prognosis than those with high expression (n=46). Low FBXO45 expression was an independent negative prognostic factor in patients with GC. Using the public Kaplan-Meier plotter database, we showed that survival in patients with low expression of FBXO45 in GC was shorter than that in those with high FBXO45 expression, regardless of lymph node metastasis. CONCLUSION: A low FBXO45 expression level in GC tissues may be a powerful predictor of poor prognosis. FBXO45 might, therefore, be a promising candidate for a molecular targeted therapy in GC.


Assuntos
Proteínas F-Box/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Idoso , Progressão da Doença , Proteínas F-Box/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo
9.
Anticancer Res ; 37(1): 343-347, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28011512

RESUMO

Endoscopic submucosal dissection (ESD) has been used to treat patients with early gastric cancer (EGC). Although several endoscopic devices have been developed to ensure easy and safe ESD, this technique still requires an experienced, highly skilled endoscopist, as it is performed through a single gastroscope, thus requiring one-handed surgical techniques. To overcome these limitations, many ESD procedures with counter-traction have been developed, such as the double scope, double channel scope, clip with line, magnetic anchor, percutaneous traction and external grasping forceps methods. We devised a double endoscopic intraluminal operation (DEILO). Two endoscopes were simultaneously inserted into the stomach. One endoscope was used to lift the lesion, and the other was used to excise the lesion. The DEILO procedure was performed on 122 cases of EGC. In this article, we report the efficacy and safety of DEILO in patients with EGC.


Assuntos
Gastroscopia/métodos , Neoplasias Gástricas/cirurgia , Dissecação , Mucosa Gástrica/cirurgia , Humanos , Neoplasias Gástricas/patologia , Resultado do Tratamento
10.
Surg Endosc ; 31(3): 1393-1401, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27444825

RESUMO

BACKGROUND: Esophagogastrostomy after proximal gastrectomy (PG) is a simple and safe reconstruction, but it leads to a high incidence of reflux esophagitis and impairs postoperative quality of life. We have already reported gastric tube (GT) reconstruction after PG and performed it on more than 100 patients. No studies have reported long-term outcomes after PG-GT. The aim of this study was to investigate long-term outcomes, including nutrition indices, such as body weight, serum albumin, total protein, hemoglobin, and ferritin after PG, and observe recovery of upper gastrointestinal tract motility. METHODS: We analyzed body weight loss and laboratory findings at our outpatient clinic at 1, 6, 12, 24, 36, 48, and 60 months postoperatively. Manometric recording was carried out at 1, 2, 3, 4, and 5 years after surgery. RESULTS: The percentage change in body weight in the PG-GT group was significantly larger than that in the PG-JI and TG-RY groups at 2.5, 3, 4, and 5 years after surgery. The levels of hemoglobin and ferritin in the PG-GT and PG-JI groups were significantly higher than those in the TG-RY group at all time points except 6 months after surgery. In the fasted state, the phase III originated at the gastric tube was propagated to the duodenum 3 years after surgery. In the fed state, phasic contractions of the duodenum were in harmony with gastric tube contractions 3 years after surgery. CONCLUSIONS: PG-GT is the least invasive procedure, and restoration of gastrointestinal motilities in the gastric tube and duodenum may ameliorate body weight loss and nutritional status, including anemia, in patients after PG.


Assuntos
Esofagostomia , Gastrectomia/métodos , Motilidade Gastrointestinal , Gastrostomia , Laparoscopia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/cirurgia , Idoso , Anemia/etiologia , Anemia/prevenção & controle , Feminino , Ferritinas/sangue , Gastrectomia/efeitos adversos , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Redução de Peso
11.
Dig Dis Sci ; 60(6): 1595-602, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25563722

RESUMO

BACKGROUND: Nesfatin-1 is a novel 82-amino acid anorectic peptide. Acute injection of nesfatin-1 into the third brain ventricle reduces food consumption during the dark phase in rats. Nesfatin-1 is also expressed in gastric X/A-like cells in the peripheral tissues. Nesfatin-1 has been reported to reduce gastric and duodenal motility and to delay gastric emptying. AIM: In the present study, we investigated the effects of nesfatin-1 on gastrointestinal motility in conscious dogs. METHODS: Force transducers were implanted onto the serosal surfaces of the gastric bodies, gastric antra, duodena, and jejuna of healthy beagle dogs, and gastrointestinal motility was monitored. We evaluated the effects of nesfatin-1 on gastrointestinal motility and on the circulating levels of nesfatin-1 in the fasted and fed states. RESULTS: The intravenous administration of nesfatin-1 reduced gastric contractions and inhibited cyclical interdigestive migrating contractions in the fasted state. In the fasted state, circulating levels of nesfatin-1 tended to increase during late phase I. In addition, the kinetics of the circulating levels of nesfatin-1 were opposite to those of ghrelin during the fasted state. CONCLUSIONS: Nesfatin-1 regulates gastrointestinal motility, and, in particular, it inhibits gastric contractions in the fasted state. Interdigestive migrating contractions may be regulated by interactions between nesfatin-1, ghrelin, and motilin.


Assuntos
Proteínas de Ligação ao Cálcio/farmacologia , Proteínas de Ligação a DNA/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Proteínas do Tecido Nervoso/farmacologia , Animais , Biomarcadores/sangue , Proteínas de Ligação ao Cálcio/sangue , Proteínas de Ligação a DNA/sangue , Cães , Ensaio de Imunoadsorção Enzimática , Jejum , Grelina/sangue , Motilina/sangue , Contração Muscular/efeitos dos fármacos , Proteínas do Tecido Nervoso/sangue , Nucleobindinas , Transdutores
12.
Surg Laparosc Endosc Percutan Tech ; 25(1): e1-e4, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24732743

RESUMO

PURPOSE: To describe our initial experiences with the standardized introducer technique for percutaneous endoscopic gastrostomy and to compare clinical outcomes and complications with the pull technique. METHODS: The introducer technique was used on 91 patients. The clinical outcomes of procedures were retrospectively collected and compared with those of 22 patients who had procedures using the pull technique. RESULTS: Mean operation time was significantly longer in the introducer technique group as compared with the pull technique group. Increased inflammation markers (body temperature, white blood cell count, and C-reactive protein) were observed in the pull technique group as compared with the introducer technique group. Incidences of peristomal infection and pneumonia were lower in the introducer method group than in the pull method group. CONCLUSIONS: The introducer technique is a useful and safe method for percutaneous endoscopic gastrostomy in terms of reduced incidences of peristomal infection, pneumonia, pain, and discomfort.


Assuntos
Endoscopia do Sistema Digestório/efeitos adversos , Endoscopia do Sistema Digestório/métodos , Nutrição Enteral/instrumentação , Gastrostomia/efeitos adversos , Gastrostomia/métodos , Técnicas de Sutura , Idoso , Proteína C-Reativa , Desenho de Equipamento , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos
13.
World J Gastroenterol ; 20(42): 15691-702, 2014 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-25400453

RESUMO

AIM: To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. METHODS: After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs. RESULTS: Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did. CONCLUSION: After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Motilidade Gastrointestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Estômago/efeitos dos fármacos , Vômito/induzido quimicamente , Animais , Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Estado de Consciência , Cães , Mucosa Gástrica/metabolismo , Humanos , Injeções Intravenosas , Secreções Intestinais/metabolismo , Intestino Delgado/inervação , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatologia , Masculino , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/metabolismo , Serotonina/administração & dosagem , Serotonina/sangue , Estômago/inervação , Estômago/fisiopatologia , Fatores de Tempo , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiopatologia , Vômito/sangue , Vômito/fisiopatologia
14.
World J Gastroenterol ; 19(39): 6604-12, 2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-24151388

RESUMO

AIM: To study the effects of 5-hydroxytryptamine (5-HT) receptor antagonists on normal colonic motor activity in conscious dogs. METHODS: Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B, 5-HT3 and 5-HT4 receptor antagonist administration. The force transducers were implanted on the serosal surfaces of the gastric antrum, terminal ileum, ileocecal sphincter and colon. Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state. The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed. RESULTS: 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum. The 5-HT3 and 5-HT4 receptor antagonists inhibited phase III of the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity. In the proximal colon, the inhibitory effect was dose dependent. Dose dependency, however, was not observed in the distal colon. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. CONCLUSION: The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.


Assuntos
Motilidade Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Receptor 5-HT2B de Serotonina/efeitos dos fármacos , Receptores 5-HT3 de Serotonina/efeitos dos fármacos , Receptores 5-HT4 de Serotonina/efeitos dos fármacos , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT4 de Serotonina/farmacologia , Animais , Colo/efeitos dos fármacos , Colo/metabolismo , Cães , Relação Dose-Resposta a Droga , Feminino , Mucosa Gástrica/metabolismo , Trato Gastrointestinal/metabolismo , Íleo/efeitos dos fármacos , Íleo/metabolismo , Masculino , Modelos Animais , Complexo Mioelétrico Migratório/efeitos dos fármacos , Receptor 5-HT2B de Serotonina/metabolismo , Receptores 5-HT3 de Serotonina/metabolismo , Receptores 5-HT4 de Serotonina/metabolismo , Estômago/efeitos dos fármacos , Fatores de Tempo , Transdutores de Pressão
15.
Nihon Geka Gakkai Zasshi ; 114(5): 236-40, 2013 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-24167975

RESUMO

Rikkunshito is a traditional Japanese medicine used to treat a variety of gastrointestinal symptoms. In several previous studies, it was demonstrated that rikkunshito stimulates gastrointestinal movement, accelerates gastric emptying, and promotes gastric adaptive relaxation. Clinically, it is known that rikkunshito attenuates dyspeptic symptoms, appetite loss, and gastroesophageal reflux after gastrointestinal surgery and in chemotherapy-induced nausea and anorexia. A recent study has demonstrated that rikkunshito affects the appetite-enhancing hormone ghrelin. Rikkunshito was also reported to increase plasma ghrelin levels and to enhance the action of ghrelin. Rikkunshito may alleviate dyspeptic symptoms after gastrointestinal surgery through its prokinetic effects and ghrelin.


Assuntos
Anorexia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Cães , Grelina/fisiologia , Humanos , Complicações Pós-Operatórias/tratamento farmacológico
16.
Carcinogenesis ; 34(10): 2314-21, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23749771

RESUMO

Karyopherin-α2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. We investigated the clinical and functional significance of KPNA2 in gastric cancer (GC). Immunohistochemistry was performed to examine KPNA2 expression in primary GC and metastatic lymph nodes. Next, KPNA2 was suppressed by small interfering RNA (siRNA) to examine KPNA2 function in proliferation and cisplatin-induced apoptosis of GC cell lines. Nuclear expression of KPNA2 in marginal regions of primary GC was stronger than in central regions of GC and normal tissues. The high expression of marginal KPNA2 was significantly associated with ß-catenin accumulation in the nucleus and poor prognosis in two independent GC cohorts (discovery cohort, n = 90, P = 0.018; validation cohort, n = 89, P = 0.0125). We detected correlations between nuclear KPNA2 expression in marginal region and progression of macroscopic type (P = 0.036), tumor depth (P = 0.013), lymph node metastasis (P = 0.0064), venous invasion (P = 0.034) and clinical stage (P = 0.0006). Nuclear KPNA2 expression in marginal regions of metastatic lymph nodes was significantly higher than in the central region. It was associated with poor survival of GC patients with lymph node metastasis (n = 96; center, P = 0.4384; marginal, P < 0.0001). KPNA2 suppression enhanced cisplatin-induced apoptosis and reduced proliferation in the KPNA2 siRNA group compared with the control siRNA group. The expression of the DNA repair gene NBS1 (NBN) in the nucleus was suppressed in KPNA2-suppressed cells. KPNA2 might be a useful prognostic marker and an effective therapeutic target for GC.


Assuntos
Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , alfa Carioferinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células , Cisplatino/farmacologia , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Antígeno Ki-67/metabolismo , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/mortalidade , alfa Carioferinas/metabolismo , beta Catenina/metabolismo
17.
J Gastroenterol ; 48(5): 611-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23053427

RESUMO

BACKGROUND: Traditional Japanese medicine, known as Kampo medicine, consists of mixtures of several medicinal herbs widely used to treat upper gastrointestinal disorders in Japan. Rikkunshito, one of these medicines, has not been evaluated with respect to its influence on gastrointestinal motor activity. We investigated the effect of rikkunshito on upper gastrointestinal motility and plasma ghrelin concentrations in conscious dogs. METHODS: Contractile response to intragastric administration of rikkunshito was studied via surgically implanted force transducers. A powdered extract of rikkunshito (1.3, 2.7, and 4.0 g) dissolved in water was administered into the stomachs of normal and vagotomized dogs before feeding and gastric emptying was evaluated. Several inhibitors of gastrointestinal motility (atropine, hexamethonium, and ondansetron) were injected intravenously before intragastric administration of rikkunshito. Plasma acylated ghrelin levels after intragastric administration of rikkunshito were measured. RESULTS: In a fasting state, intragastric administration of rikkunshito induced phasic contractions in the duodenum and jejunum in normal dogs. Rikkunshito-induced contractions were inhibited by atropine, hexamethonium and ondansetron. In vagotomized dogs, rikkunshito induced phasic contractions, similar to normal dogs. Gastric emptying was accelerated by intragastric administration of rikkunshito in a dose-dependent manner. The plasma acylated ghrelin level 150 min after intragastric administration of 4.0 g of rikkunshito was significantly higher than the control value. CONCLUSIONS: Intragastric administration of rikkunshito stimulates gastrointestinal contractions in the interdigestive state through cholinergic neurons and 5-HT type 3 receptors. Moreover, rikkunshito increases plasma acylated ghrelin levels. Rikkunshito may alleviate gastrointestinal disorders through its prokinetic effects.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Grelina/sangue , Animais , Estado de Consciência , Cães , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Masculino , Medicina Kampo , Estômago
18.
Am J Physiol Regul Integr Comp Physiol ; 302(2): R233-41, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22071157

RESUMO

During fasting, gastrointestinal (GI) motility is characterized by cyclical motor contractions. These contractions have been referred to as interdigestive migrating contractions (IMCs). In dogs and humans, IMCs are known to be regulated by motilin. However, in rats and mice, IMCs are regulated by ghrelin. It is not clear how these peptides influence each other in vivo. The aim of the present study was to investigate the relationship between ghrelin and motilin in conscious dogs. Twenty healthy beagles were used in this study. Force transducers were implanted in the stomach, duodenum, and jejunum to monitor GI motility. Subsequent GI motility was recorded and quantified by calculating the motility index. In examination 1, blood samples were collected in the interdigestive state, and levels of plasma ghrelin and motilin were measured. Plasma motilin peaks were observed during every gastric phase III, and plasma ghrelin peaks occurred in nearly every early phase I. Plasma motilin and ghrelin levels increased and decreased cyclically with the interdigestive states. In examination 2, saline or canine ghrelin was administered intravenously during phase II and phase III. After injection of ghrelin, plasma motilin levels were measured. Ghrelin injection during phases II and III inhibited phase III contractions and decreased plasma motilin levels. In examination 3, ghrelin was infused in the presence of the growth hormone secretagogue receptors antagonist [D-Lys3]-GHRP-6. Continuous ghrelin infusion suppressed motilin release, an effect abrogated by the infusion of [D-Lys3]-GHRP-6. Examination 4 was performed to evaluate the plasma ghrelin response to motilin administration. Motilin infusion immediately decreased ghrelin levels. In this study, we demonstrated that motilin and ghrelin cooperatively control the function of gastric IMCs in conscious dogs. Our findings suggest that ghrelin regulates the function and release of motilin and that motilin may also regulate ghrelin.


Assuntos
Duodeno/fisiologia , Grelina/sangue , Jejuno/fisiologia , Motilina/sangue , Complexo Mioelétrico Migratório/fisiologia , Estômago/fisiologia , Animais , Cães , Duodeno/efeitos dos fármacos , Grelina/farmacologia , Jejuno/efeitos dos fármacos , Complexo Mioelétrico Migratório/efeitos dos fármacos , Estômago/efeitos dos fármacos
19.
J Gastrointest Surg ; 15(8): 1361-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21607794

RESUMO

BACKGROUND AND AIMS: Postoperative ileus is a transient bowel dysmotility that occurs following many types of operations and is a common complication of gastrointestinal surgery. Mosapride citrate is an agonist of the 5-hydroxytryptamine 4 receptor and accelerates upper gut motility. No study has evaluated its effect on gastrointestinal motility after surgery. The aim of this study was to investigate whether mosapride citrate reduces the duration of postoperative ileus. METHODS: Thirty patients with colon cancer who underwent colectomy were divided into two groups: the mosapride group and the control group. The mosapride group received mosapride 15 mg by mouth with a minimal amount of water three times a day, starting on postoperative day 1. The control group received only a minimal amount of water on the same schedule. Patients were allowed to resume oral feeding on postoperative day 4. Postoperative time to first flatus and defecation were evaluated, and the amount of food intake was observed. Gastrointestinal motility was recorded on postoperative day 8. RESULTS: The appearance ratio of interdigestive migrating contractions and the motility index at the antrum and duodenum were significantly higher in the mosapride group than in the control group. The time to first flatus and defecation were significantly shorter in the mosapride group than in the control group. The amount of food intake on postoperative days 6 and 7 was significantly larger in the mosapride group than in the control group. CONCLUSION: Mosapride citrate reduces the duration of postoperative ileus and may improve outcomes after gastrointestinal surgery.


Assuntos
Benzamidas/uso terapêutico , Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Fármacos Gastrointestinais/uso terapêutico , Íleus/tratamento farmacológico , Morfolinas/uso terapêutico , Idoso , Benzamidas/farmacologia , Defecação , Feminino , Flatulência , Fármacos Gastrointestinais/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Íleus/etiologia , Masculino , Pessoa de Meia-Idade , Morfolinas/farmacologia , Método Simples-Cego , Fatores de Tempo
20.
World J Surg ; 35(4): 805-10, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21279511

RESUMO

BACKGROUND: Postoperative ileus (POI) is one of the most common complications of gastrointestinal surgery. The present study was performed to evaluate the effects of glutamine administration on POI after gastric surgery in humans. SUBJECTS AND METHODS: The subjects were 31 patients who underwent partial distal gastrectomy for gastric cancer and who were randomly assigned to one of two groups based on postoperative treatment: the glutamine group (3 g/day) and the control group. Manometric recording was done 12 days after surgery, and plasma glutamine concentrations were measured preoperatively and on postoperative day 12. RESULTS: Motor activities of the duodenum in the glutamine group were significantly greater than those of the control group in the interdigestive state. The incidence of phase III motor activity (interdigestive migrating motor contractions) in the glutamine group was significantly higher than that in the control group (60 versus 19%). The glutamine group showed a significantly smaller decrease of plasma glutamine levels compared with the control group. CONCLUSIONS: Glutamine could act as a motility-recovery agent after gastrectomy in humans.


Assuntos
Gastrectomia/métodos , Esvaziamento Gástrico/efeitos dos fármacos , Glutamina/administração & dosagem , Neoplasias Gástricas/cirurgia , Administração Oral , Idoso , Análise de Variância , Feminino , Seguimentos , Gastrectomia/efeitos adversos , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Japão , Masculino , Manometria , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Pós-Operatórios/métodos , Valores de Referência , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do Tratamento
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