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INTRODUCTION: Beckwith-Wiedemann syndrome (BWS) manifests distinctive features, such as macroglossia, overgrowth, and abdominal wall defects. In this report, we describe a case of BWS in an extremely low birth weight infant diagnosed at three months after birth because of the intensive care for low birth weight. PRESENTATION OF CASE: A female infant was delivered at 24 weeks and 6 days of gestation with a weight of 845 g. After birth, significant small intestinal intra-umbilical prolapse was observed, and abdominal wall closure using a sutureless method was performed on day zero. Careful neonatal management was performed; however, an episode of bloody stools led to a diagnosis of intestinal volvulus due to intestinal malrotation. At 119 days of age, the Ladd procedure was performed. Notably, during anaesthesia induction, features suggestive of BWS were observed, leading to its diagnosis. DISCUSSION: Early diagnosis of BWS is vital because of its association with tumors. However, because she was an extremely low birth weight infant who required oral intubation and supine management for respiratory control, nevus flammeus and macroglossia were not observed. Therefore, BWS was not diagnosed for approximately three months after birth. It is important to recognize that omphalocele in extremely low birth weight infants is a risk factor for delayed diagnosis of BWS. CONCLUSION: Timely diagnosis of BWS is critical because of its association with tumors and varied clinical presentations. Early screening, especially for tumors, and awareness among surgical practitioners can aid in timely interventions and improved patient outcomes.
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INTRODUCTION: Oesophageal atresia, duodenal atresia, and anorectal malformations are rare. This report describes a case of an infant with these three conditions treated using a multi-stage surgical procedure. PRESENTATION OF CASE: A male infant was delivered via caesarean section at 34 weeks and 4 days of gestation, weighing 1709 g. Radiography at birth showed a coil-up of the gastrointestinal tube in the oesophagus, a double bubble sign; the patient was subsequently diagnosed with gross type C oesophageal atresia with duodenal atresia. A gastrostomy was performed at day 0. Oesophago-oesophageal anastomosis was performed after tracheoesophageal fistula and blind-end dissection. A duodeno-duodenal diamond-shaped anastomosis was performed, and a tube enterostomy was created from the gastric area near gastrostomy as a trans-anastomotic feeding tube. A colostomy was performed in the descending colon owing to a non-rotation-type anomaly of intestinal malrotation. After other multi-stage surgeries and weight gain, posterior sagittal anorectoplasty was performed at age 1 year 2 months. DISCUSSION: Triple atresia (TA), characterized by triumvirate oesophageal atresia, duodenal atresia, and anorectal malformations, remains a clinical puzzle. Notably, standardized therapeutic guidelines for managing TA are lacking. The complexity of this constellation of anomalies necessitates astute diagnostic acumen and strategic treatment planning. CONCLUSION: Our patient showed a favourable clinical course with an accurate and timely diagnosis, serving as an experience for an innovative multi-stage therapeutic strategy. Our case showed the appropriate challenges of TA while illuminating the potential for successful outcomes through meticulous clinical management.
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INTRODUCTION: Right congenital diaphragmatic defect (CDH) has been reported poor prognosis. However, laterality of the defect as the prognostic factor is recent controversial topic. We experienced two cases of right CDH with relatively stable respiratory condition and good clinical course. PRESENTATION OF CASES: Case 1 was a girl diagnosed with right CDH by fetal ultrasonography and delivered by planned caesarian section at 37 weeks, 3 days. Fetal MRI showed liver herniation into the right thoracic cavity. High frequency oscillatory ventilation with nitric oxide gas was administered until day 5. At surgery on day 8, we found defects in the right posterolateral diaphragm and sac herniation of the right side of the liver into the right thoracic cavity. The postsurgical course was uneventful, and she was discharged on day 41. Case 2 was a girl with suspected congenital jejunal atresia after fetal ultrasonography detected polyhydramnios and dilatation. She was delivered by normal vaginal delivery at 38 weeks, 5 days, and thoraco-abdominal X ray showed right CDH but no small intestinal atresia. Surgery performed on day 3 found liver herniation into the diaphragmatic defect. Subsequently, bacterial infection occurred and was treated with the antibiotics, but her respiratory condition remained stable. She was discharged on day 49. DISCUSSION: The volume of herniated abdominal organs is affected by the presence of a hernia sac or the size of the diaphragmatic defect. CONCLUSION: The size of diaphragmatic defect, but not the laterality of the diaphragmatic defect, may be an important prognostic factor in right CDH.
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A female newborn weighing 542 g and delivered at 27 weeks gestation presented with bilateral inguinal hernias while in the neonatal intensive care unit. Ultrasonography confirmed herniation of the uterus into the right inguinal hernia without signs of incarceration. Due to the absence of complications, she was discharged and scheduled for follow-up at the outpatient clinic. At 11 months of age, a subsequent ultrasonography showed only omental herniation, with no evidence of uterine prolapse. When she reached 1 year of age, a laparoscopic percutaneous extraperitoneal closure procedure was performed. During the surgery, it was observed that the uterus and fallopian tubes were located near the hernia orifice, but no clear prolapse was detected. The procedure concluded safely with successful high ligation. It has noted that in cases of uterine prolapse hernias, the uterus tends to recede as the child grows, which supports the decision to delay surgery for improved safety.
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INTRODUCTION: Tumor-infiltrating cells play an important role in tumor immunology, and tumor-infiltrating lymphocytes (TILs) are critical in antitumor reaction related to immune checkpoint inhibition targeting programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1). METHODS: In nude mice, which are immune deficient because they lack T cells, and inbred A/J mice, which are syngeneic to neuroblastoma cells (Neuro-2a) and have normal T cell function, we investigated the importance of T lymphocytes in immune checkpoint inhibition in mouse neuroblastoma and analyzed the immune cells in the tumor microenvironment. Then, we subcutaneously injected mouse Neuro-2ainto nude mice and A/J mice, administered anti-PD-1 and anti-PD-L1 antibodies by intraperitoneal injection, and evaluated tumor growth. At 16 d after Neuro-2a cells injection, mice were euthanized, tumors and spleens were harvested, and immune cells were analyzed by flow cytometry. RESULTS: The antibodies suppressed tumor growth in A/J but not in nude mice. The co-administration of antibodies did not affect regulatory T cells (culster of differentiation [CD]4+CD25+FoxP3+ cells) or activated CD4+ lymphocytes (expressing CD69). No changes in activated CD8+ lymphocytes (expressing CD69) were observed in spleen tissue. However, increased infiltration of activated CD8+ TILs was seen in tumors weighing less than 300 mg, and the amount of activated CD8+ TILs was negatively correlated with tumor weight. CONCLUSIONS: Our study confirms that lymphocytes are essential for the antitumor immune reaction induced by blocking PD-1/PD-L1 and raises the possibility that promoting the infiltration of activated CD8+ TIL into tumors may be an effective treatment for neuroblastoma.
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Inhibidores de Puntos de Control Inmunológico , Neuroblastoma , Ratones , Animales , Ratones Desnudos , Antígeno B7-H1/metabolismo , Linfocitos T , Neuroblastoma/tratamiento farmacológico , Microambiente TumoralRESUMEN
BACKGROUND: Immunotherapy may improve the poor prognosis of high-risk neuroblastoma. Programmed cell death-1 (PD-1) is expressed in several cancers. The tyrosine hydroxylase MYCN (TH-MYCN) transgenic mouse model is widely used in neuroblastoma research, but detailed information on its immunological background is lacking. Therefore, we studied the immunological tumor microenvironment and tumor cell surface antigen expression in homozygote and hemizygote mice and effects of antibody therapy against PD-1. METHODS: CD4, CD8, CD11b, and CD11c expression in immune cells from retroperitoneal lymph nodes and spleen was analyzed by flow cytometry. Tumor cell surface antigen expression was confirmed, and data from homozygote and hemizygote mice were compared. Effects of anti-PD-1 antibody were evaluated. RESULTS: CD4-, CD8-, CD11b-, and CD11c-positive cells were not significantly different in homozygote and hemizygote mice, and CD11b- and CD11c-positive cells were identified in the tumor microenvironment in both. Tumor cells expressed PD-1, and anti-PD-1 antibody had anti-tumor effects and significantly reduced the percentage of living tumor cells in cultures after 2 h. CONCLUSION: The immunological background is similar in homozygote and hemizygote TH-MYCN transgenic mice, and both have PD-1-positive tumor cells. Anti-PD-1 antibody suppresses tumor growth. This mouse model may be a useful for studying immunotherapy of neuroblastoma.
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Neuroblastoma , Tirosina 3-Monooxigenasa , Animales , Ratones , Antígenos de Superficie , Apoptosis , Modelos Animales de Enfermedad , Ratones Transgénicos , Proteína Proto-Oncogénica N-Myc/genética , Microambiente TumoralRESUMEN
A 19-year-old woman underwent prenatal ultrasonography, which confirmed the presence of an isolated cystic mass in the upper abdominal cavity of a fetus. A female infant weighing 3085 g was delivered at 36 weeks' gestation. Ultrasonography and computed tomography examination revealed a clear unilocular cyst and occupying the right side of the abdomen. The infant's respiratory status was unstable, and she fed poorly, owing to compression by the hepatic cyst. We performed ultrasound-guided aspiration of a hepatic cyst at 15 days old, but it rapidly re-grew. Therefore, we performed laparoscopic findings and fenestration of the hepatic cyst via an umbilical arc incision and the cyst wall was excised at 43 days old. The histopathological diagnosis was mesothelial cell-derived hepatic cyst. Three years after the operation, no recurrence has been observed. Hepatic cyst fenestration by umbilical incision can be performed safely in infants and it is a cosmetically superior method.
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Fetal thoracoamniotic shunting (TAS), which drains pleural effusion, is a treatment for severe primary fetal pleural effusion. While TAS is an effective treatment, its complications include bleeding and the catheter becoming dislodged, and also penetrating the thoracic cavity or chest wall. Catheters dislodged into the thoracic cavity in TAS can be removed by thoracoscopy. However, if there are adhesions in the thoracic cavity, finding the TAS catheter with a thoracoscope can be difficult. We used fluoroscopic radiography in addition to a thoracoscope to remove a TAS catheter in four patients. A 5-mm trocar was inserted into the thoracic cavity, and a 2.7-mm scope and 3-mm forceps were inserted into the trocar. We searched for TAS catheters using a thoracoscope and fluoroscopic radiography. If there are adhesions in the thoracic cavity and removing the TAS catheter is difficult, the combined use of a thoracoscope and fluoroscopic radiography may prove helpful.
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Catéteres , Derrame Pleural , Drenaje , Humanos , Recién Nacido , Derrame Pleural/terapia , Toracoscopía , Resultado del TratamientoRESUMEN
PURPOSE: We aimed to clarify the frequency and the clinical significance of deviation of the uterus in female pediatric inguinal hernia. METHODS: We retrospectively evaluated the data of 94 female pediatric inguinal hernia cases that were treated by laparoscopic percutaneous extraperitoneal closure. We assessed for correlations between uterine deviation and age, body weight, the size of the hernia orifice, and the presence of contralateral processus vaginalis (PV) patency. RESULTS: Eighty-four of 94 cases were diagnosed with unilateral inguinal hernia. A total of 62 (73.8%) of these had uterine deviation to the hernia side (Group D); 22 (26.2%) had no deviation to the hernia side (Group N) (P < 0.001). Group D cases were significantly younger than those in Group N (P = 0.0351). There was no difference in body weight, size of the hernia orifice, or contralateral PV patency between the two groups. CONCLUSION: The incidence of uterine deviation toward the hernia side was statistically significant. It is important to recognize that female pediatric inguinal hernia repair carries an increased risk of ovarian and fallopian tube damage, because these appendages are close to the hernia orifice as a result of the uterine deviation.
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Hernia Inguinal , Laparoscopía , Peso Corporal , Niño , Femenino , Hernia Inguinal/epidemiología , Hernia Inguinal/cirugía , Herniorrafia , Humanos , Lactante , Estudios Retrospectivos , Útero/cirugíaRESUMEN
[This corrects the article DOI: 10.3892/br.2015.546.].
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BACKGROUND: Most tumors responding to immunotherapy with monoclonal antibodies targeting programmed cell death protein1 (PD1) and programmed death ligand-1 (PD-L1) show surface expression of PD-L1. Neuroblastoma has been reported to show low PD-L1 surface expression. METHODS: The effect of immune checkpoint inhibitor on mouse neuroblastoma was investigated, and host immune cells were analyzed in the tumor microenvironment. Expression of co-stimulatory molecules by Neuro-2a mouse neuroblastoma cells was analyzed using flow cytometer. Neuro-2a cells were inoculated subcutaneously into A/J mice, followed by intraperitoneal injection of antibodies targeting PD-1 and PD-L1. Mice were sacrificed for the measurement of tumor weights on day 14 following tumor inoculation, and tumor-infiltrating cells were analyzed using a flow cytometer. RESULTS: Dim expression of PD-L1 was observed on the cell surface of cultured Neuro-2a cells. Growth of subcutaneous tumors was significantly suppressed, and PD-L1-expressing tumor cells were depleted by the antibody treatment. We confirmed that Neuro-2a cells opsonized by the anti-PD-L1 antibody were phagocytosed in the in vitro setting. In the treated tumor microenvironments, CD8α+ lymphocyte and CD11c+ MHC II+ cells were significantly accumulated in comparison with the control group. These CD11c+ MHC II+ cells expressed CD80, CD86, CD14, and CD40, but not CD205, PD-L1, or CTLA4. PD-1 expression was detected dimly. Immune suppressive effects of CD11b+Gr-1+ myeloid-derived suppressor cells by the administration of anti-PD-1 and PD-L1 antibodies were not observed in spleen, regional lymph nodes, or tumor microenvironment. CONCLUSIONS: Our findings raise the possibility that co-administration of anti-PD-1 and anti-PD-L1 antibodies have a synergistic effect on inhibition of tumor growth and could be an effective therapy against neuroblastoma with dim expression of PD-L1.
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Antineoplásicos Inmunológicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Antígeno B7-H1/análisis , Células Dendríticas/inmunología , Neuroblastoma/tratamiento farmacológico , Animales , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Línea Celular Tumoral/trasplante , Células Dendríticas/efectos de los fármacos , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Femenino , Citometría de Flujo , Humanos , Ratones , Neuroblastoma/inmunología , Neuroblastoma/patología , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Receptor de Muerte Celular Programada 1/análisis , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunologíaRESUMEN
PURPOSE: Combining antitumor immunotherapy with conventional intensive multimodal therapy may be considered for advanced neuroblastoma. We investigated combination therapy with ex vivo generated immunostimulatory cells and intraperitoneal doxorubicin. METHODS: Immunogenic death of neuro-2a neuroblastoma cells was induced by doxorubicin or cisplatin (negative control). Mouse bone marrow cells were cultured with granulocyte-macrophage colony-stimulating factor, followed by addition of doxorubicin-killed neuro-2a cells with or without interleukin-4 and/or CpG-oligodeoxynucleotide to induce immunostimulatory cells. CD8α+ lymphocytes were cocultured with killed neuro-2a cells and immunostimulatory cells, and interferon-γ was measured in the supernatant. Furthermore, female A/J mice were injected with viable neuro-2a cells, followed by immunostimulatory cells and doxorubicin. Then intraabdominal tumor nodules were evaluated. RESULTS: Bone marrow-derived immunostimulatory cells only promoted interferon-γ production by CD8α+ lymphocytes after first being stimulated by doxorubicin-killed neuro-2a cells and interleukin-4, followed by CpG-oligodeoxynucleotide. These cells had a surface antigen expression profile compatible with activated dendritic cells and suppressed tumors in mice intravenously injected with neuro-2a cells. Despite a similar surface antigen profile, the in vivo antitumor effect was stronger after injection of immunostimulatory cells induced by doxorubicin-killed neuro-2a cells compared with cells induced by cisplatin-killed neuro-2a cells. Moreover, interferon-γ production was greater when CD8α+ lymphocytes were cocultured with doxorubicin-killed neuro-2a cells and immunostimulatory cells rather than with cisplatin-killed cells. CONCLUSION: Cells with antitumor activity can be induced from bone marrow cells. Combining such cells with doxorubicin may activate antitumor immunity in tumor-bearing mice. Interactions between induced immunostimulatory cells and conventional chemotherapy might be important for antitumor immunity.
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Antineoplásicos/farmacología , Células de la Médula Ósea/fisiología , Inmunoterapia Adoptiva , Neuroblastoma/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Células de la Médula Ósea/efectos de los fármacos , Terapia Combinada , Doxorrubicina/farmacología , Femenino , Ratones , Modelos Animales , Neuroblastoma/patologíaAsunto(s)
Contenido Digestivo , Ileostomía/efectos adversos , Perforación Intestinal/cirugía , Femenino , Humanos , Ileostomía/métodos , Recién Nacido de Bajo Peso , Recién Nacido , Intestino Delgado/fisiopatología , Intestino Delgado/cirugía , Masculino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Reciclaje/métodos , Estomas Quirúrgicos/efectos adversosRESUMEN
The antigen-presenting capacity of specific cells and tumor immunogenicity involved in innate cellular immunity are important for initiating an antitumor response to advanced neuroblastoma. The present study was performed to establish a method of producing antigen-presenting cells that induced an immune response to murine neuroblastoma cells through culture with neuroblastoma cells that had undergone immunogenic cell death. Immunogenic death of neuro-2a murine neuroblastoma cells was induced by exposure to doxorubicin. Mouse bone marrow cells were cultured in medium containing granulocyte-macrophage colony-stimulating factor, followed by the addition of doxorubicin-treated neuro-2a cells to the culture with or without lipopolysaccharide (LPS) and/or interleukin-4. Subsequently, cluster of differentiation (CD) 8α+ lymphocytes were co-cultured with neuro-2a cells and the adherent bone marrow cells obtained by the above procedure to evaluate CD8α+ lymphocyte proliferation and interferon-γ production. Furthermore, the surface antigen profile of adherent bone marrow cells was analyzed by flow cytometry. When adherent bone marrow cells were treated with LPS and/or interleukin-4, followed by co-culture with CD8α+ lymphocytes and neuro-2a cells, interferon-γ production by the CD8α+ cells increased in response to anti-CD3/CD28 antibody stimulation. CD11c major histocompatibility complex II (MHC II) double-positive cells were increased among adherent cells derived from cultured bone marrow cells. These cells were positive for DEC-205, but not CD8α. These findings suggest that co-culture of bone marrow-derived cells with tumor cells (that have undergone immunogenic death by exposure to doxorubicin) plus stimulation by LPS and interleukin-4 induces antigen-presenting cells that can evoke an immune response to neuroblastoma. Bone marrow-derived DEC-205+ CD11c+ MHC II+ dendritic cells are key antigen-presenting cells in the induction of an immune response following phagocytosis of doxorubicin-treated neuroblastoma cells.
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BACKGROUND: We reported two rare cases of congenital diaphragmatic hernia with abdominal wall closure defect, which were not associated with septum transversum diaphragmatic defects or Fryns syndrome. CASE PRESENTATION: Case 1: a Japanese baby boy was delivered at 37 weeks' gestation by urgent cesarean section because of the diagnosis of severe fetal distress. Congenital diaphragmatic hernia with omphalocele was prenatally diagnosed with fetal ultrasound. A ruptured omphalocele was confirmed at delivery. A silo was established on the day of his birth; direct closure of his diaphragmatic defect and abdominal wall closure was performed on the fifth day after his birth. Trisomy 13 was confirmed by genetic examination. His postoperative course was uneventful and he was discharged 5 months postnatally with home oxygen therapy. He was readmitted because of heart failure and died at 6 months. Case 2: a Japanese baby boy, who was prenatally diagnosed with gastroschisis, was delivered at 35 weeks' gestation by urgent cesarean section because of the diagnosis of fetal distress. Silo construction using a wound retractor was performed on the day of his birth and direct abdominal closure was performed on the tenth day after his birth. Trisomy 21 was confirmed by genetic examination. Treatment for his respiratory distress was continued after surgery. A retrosternal hernia was revealed at 6 months and direct closure of retrosternal diaphragm with the resection of hernia sac was performed. His postoperative course was uneventful and he was discharged with home oxygen therapy. CONCLUSIONS: Attention should be paid to chromosomal abnormality in cases in which the coexistence of congenital diaphragmatic hernia and abdominal wall closure defect are observed.
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Pared Abdominal/anomalías , Aberraciones Cromosómicas , Síndrome de Down/diagnóstico , Cardiopatías Congénitas/complicaciones , Hernia Umbilical/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/complicaciones , Resultado Fatal , Cardiopatías Congénitas/patología , Cardiopatías Congénitas/terapia , Insuficiencia Cardíaca/etiología , Hernia Umbilical/complicaciones , Hernias Diafragmáticas Congénitas/patología , Hernias Diafragmáticas Congénitas/terapia , Humanos , Recién Nacido , Cariotipificación , Masculino , Ultrasonografía PrenatalRESUMEN
We report a case of acute acalculous cholecystitis with eosinophilic infiltration. A previously healthy 6-year-old boy was referred with right abdominal pain. Imaging demonstrated marked thickening of the gallbladder wall and peri-cholecystic effusion. Acute acalculous cholecystitis was diagnosed. Symptoms persisted despite conservative treatment, therefore cholecystectomy was performed. Pathology indicated infiltration of eosinophils into all layers of the gallbladder wall. The postoperative course was uneventful and the patient has had no further symptoms. Eosinophilic cholecystitis is acute acalculous cholecystitis with infiltration of eosinophils. The causes include parasites, gallstones, allergies, and medications. In addition, it may be seen in conjunction with eosinophilic gastroenteritis, eosinophilic pancreatitis, or both. An allergic reaction to abnormal bile is thought to be the underlying cause. The present case did not fulfill the diagnostic criteria of eosinophilic cholecystitis, but this may have been in the process of developing.
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Colecistitis Alitiásica/complicaciones , Eosinofilia/complicaciones , Eosinófilos/patología , Vesícula Biliar/patología , Colecistitis Alitiásica/diagnóstico por imagen , Enfermedad Aguda , Niño , Colangiografía , Eosinofilia/diagnóstico por imagen , Vesícula Biliar/citología , Humanos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
This study aimed to determine whether bafilomycin A1 (Baf-A1), a vacuolar H-ATPase inhibitor, could promote an immune response after the induction of apoptosis in mouse neuroblastoma cells. Mouse neuro-2a cells were cultured in a medium containing Baf-A1, and apoptosis was evaluated by flow cytometry. To examine the influence in the phagocytic cell, CD11b spleen cells or bone marrow-derived dendritic cells (BM-DCs) were cocultured with Baf-A1-treated neuro-2a. Interferon-γ (IFN-γ) production was used as an index of the immune response, and CDDP was used as the negative control. When CD8α cells were cocultured with CD11b cells and Baf-A1-treated neuro-2a cells in the presence of CpG-oligodeoxynucleotide (CpG-ODN) (a toll-like receptor 9 [TLR-9] agonist), CD8α lymphocyte proliferation and secretion of IFN-γ were observed. Phagocytosis of apoptotic cells by BM-DCs was maximal after simultaneous stimulation with CpG-ODN and lipopolysaccharide (LPS; a TLR-4 agonist). IFN-γ secretion was maximal when Baf-A1-treated neuro-2a cells and CD8α lymphocytes were cocultured with BM-DCs and stimulated with CpG-ODN. In contrast, IFN-γ production was not increased when the cells were cultured with LPS. When cells were stimulated with both CpG-ODN and LPS, promotion of IFN-γ production by CpG-ODN was suppressed. Induction of apoptosis by Baf-A1 could possibly enhance antitumor immunity in patients receiving chemotherapy for neuroblastoma. Stimulation of BM-DCs with a TLR-9 agonist could promote antitumor activity after Baf-A1 treatment.
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Apoptosis/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Inhibidores Enzimáticos/farmacología , Macrólidos/farmacología , Neuroblastoma/patología , Fagocitosis/fisiología , Animales , Células Presentadoras de Antígenos/inmunología , Células de la Médula Ósea , Linfocitos T CD8-positivos/patología , Proliferación Celular , Técnicas de Cocultivo , Femenino , Citometría de Flujo , Humanos , Inmunidad Celular/inmunología , Interferón gamma/metabolismo , Lipopolisacáridos/farmacología , Activación de Linfocitos , Ratones , Ratones Endogámicos A , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/inmunología , Oligodesoxirribonucleótidos/farmacología , Células Tumorales CultivadasRESUMEN
The aim of this study was to compare the ability of the drugs doxorubicin and Bafilomycin-A1(Baf-A1)to promote an immune reaction following the induction of cell death in a mouse neuroblastoma model. Neuro-2a cells were cultured in medium containing doxorubicin or Baf-A1. Bone marrow-derived dendritic cells(BM-DCs)were co-cultured with neuro-2A cells that were grown in doxorubicin- or Baf-A1-containing media, and phagocytosis of neuro-2a cells by the BN-DCs was evaluated. Additionally, dead neuro-2a cells were co-cultured with CD8a + lymphocytes and BM-DCs, and the proliferation of CD8a + cells was evaluated. Interferon-g(IFN-g)production was used as an indexof the immune response. Dead neuro-2a cells treated with doxorubicin were phagocytosed effectively compared to the cells treated with Baf-A1. However, phagocytosis of cells treated with Baf-A1 was promoted after stimulation with CpG oligodeoxynucleotide (CpG-ODN). When CD8a + cells were co-cultured with BM-DCs and doxorubicin-treated neuro-2a cells, CD8a + lymphocyte proliferation was observed. There was no statistical difference in IFN-g secretion between the doxorubicin-treated and Baf-A1-treated cells. However, after stimulation by CpG-ODN, IFN-g production was more effectively observed in the Baf-A1-treated cells. Induction of cell death by doxorubicin or Baf-A1 could possibly enhance antitumor immunity in patients receiving chemotherapy for neuroblastoma. Selection of anti-tumor agents and stimulation of BM-DCs with a toll-like receptor (TLR) agonist is considered important in promoting antitumor activity after chemotherapy.