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Elevated autophagy activity enhances the malignancy of pancreatic cancer (PaCa), and autophagy is recognized as a novel therapeutic target. Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a transcription factor that suppresses autophagy, but its association with PaCa is unknown. We analyzed the function of ZKSCAN3 in PaCa and investigated whether autophagy regulation through ZKSCAN3 could become a new therapeutic target for PaCa. Using reverse transcription-quantitative polymerase chain reaction and western blotting, we observed that ZKSCAN3 expression was upregulated in several PaCa cell lines compared with normal pancreatic ductal epithelial cells. Additionally, comparing ZKSCAN3 expression with the prognosis of PaCa patients using web databases, we found that higher ZKSCAN3 expression in PaCa was associated with extended overall survival. Knocking down ZKSCAN3 promoted the proliferation of PaCa cells. Moreover, following ZKSCAN3 knockdown, PaCa cells exhibited significantly enhanced migratory and invasive properties. Conversely, overexpression of ZKSCAN3 significantly suppressed the proliferation, migration and invasion of PaCa cells. Additionally, the knockdown of ZKSCAN3 increased the expression of LC3-II, a marker of autophagy, whereas ZKSCAN3 overexpression decreased LC3-II expression. In a xenograft mouse model, tumors formed by MIA PaCa-2 cells in which ZKSCAN3 was knocked down significantly increased in size compared with the control group. In conclusion, ZKSCAN3 expression was upregulated in several pancreatic cancer cells. Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa.
Assuntos
Autofagia , Movimento Celular , Proliferação de Células , Invasividade Neoplásica , Neoplasias Pancreáticas , Fatores de Transcrição , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Autofagia/genética , Animais , Proliferação de Células/genética , Movimento Celular/genética , Linhagem Celular Tumoral , Camundongos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Prognóstico , Feminino , Técnicas de Silenciamento de Genes , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genéticaRESUMO
We previously established pancreatic cancer (PaCa) cell lines resistant to gemcitabine and found that the activity of nuclear factor κB (NF-κB) was enhanced upon the acquisition of gemcitabine resistance. Parthenolide, the main active ingredient in feverfew, has been reported to exhibit antitumor activity by suppressing the NF-κB signaling pathway in several types of cancers. However, the antitumor effect of parthenolide on gemcitabine-resistant PaCa has not been elucidated. Here, we confirmed that parthenolide significantly inhibits the proliferation of both gemcitabine-resistant and normal PaCa cells at concentrations of 10 µM and higher, and that the NF-κB activity is significantly inhibited, even by 1 µM parthenolide. In Matrigel invasion assays and angiogenesis assays, the invasive and angiogenic potentials were higher in gemcitabine-resistant than normal PaCa cells and were inhibited by a low concentration of parthenolide. Furthermore, Western blotting showed suppressed MRP1 expression in gemcitabine-resistant PaCa treated with a low parthenolide concentration. In a colony formation assay, the addition of 1 µM parthenolide improved the sensitivity of gemcitabine-resistant PaCa cell lines to gemcitabine. These results suggest that parthenolide may be used as a novel therapeutic agent for the treatment of gemcitabine-resistant PaCa.
Assuntos
Gencitabina , Neoplasias Pancreáticas , Sesquiterpenos , Humanos , NF-kappa B/metabolismo , Desoxicitidina/farmacologia , Angiogênese , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Neoplasias Pancreáticas/tratamento farmacológicoRESUMO
BACKGROUND: Neurofibromatosis type 1 is an autosomal-dominant disease characterized by café-au-lait spots and neurofibromas, as well as various other symptoms in the bones, eyes, and nervous system. Due to its connection with vascular fragility, neurofibromatosis type 1 has been reported to be associated with vascular lesions, such as aneurysms. However, there have been few reports of abdominal visceral aneurysms associated with neurofibromatosis type 1. Furthermore, there have been no reports of robotic treatment of aneurysms associated with neurofibromatosis type 1. In this report, we describe the case of a patient with neurofibromatosis type 1 with a splenic artery aneurysm who was successfully treated with robotic surgery. CASE PRESENTATION: This report describes a 41-year-old Asian woman with a history of neurofibromatosis type 1 who was referred to our hospital for evaluation of a 28 mm splenic artery aneurysm observed on abdominal ultrasound. The aneurysm was in the splenic hilum, and transcatheter arterial embolization was attempted; however, this was difficult due to the tortuosity of the splenic artery. Thus, we suggested minimally invasive robotic surgery for treatment and resection of the splenic artery aneurysm with preservation of the spleen. The postoperative course was uneventful, and the patient was discharged on the eighth day after surgery. At 1 year of follow-up, the patient was doing well, with no evidence of recurrence. CONCLUSION: We encountered a rare case of splenic artery aneurysm in a patient with neurofibromatosis type 1 who was successfully treated with robotic surgery. There is no consensus on treatment modalities for neurofibromatosis-related aneurysms, and endovascular treatment is considered safe and effective; however, surgery remains an important treatment modality. Especially in patients with stable hemodynamic status, robotic surgery may be considered as definitive treatment. To our knowledge, this is the first successfully treated case of a splenic artery aneurysm in a patient with neurofibromatosis type 1.
Assuntos
Aneurisma , Neurofibromatose 1 , Procedimentos Cirúrgicos Robóticos , Adulto , Feminino , Humanos , Aneurisma/complicações , Aneurisma/diagnóstico por imagem , Aneurisma/cirurgia , Neurofibromatose 1/complicações , Artéria Esplênica/diagnóstico por imagem , Artéria Esplênica/cirurgia , Procedimentos Cirúrgicos VascularesRESUMO
The frequency of metastasis to the pancreas is limited, and the frequency of metastasis of a squamous cell carcinoma of the esophagus is limited even further. The curative resection of this type of metastatic lesion has been reported for some patients; however, the survival benefit that can be attributed to these procedures has not yet been clearly determined. The patient examined in the present study was a 54-year-old man who was diagnosed with a lower thoracic esophageal cancer. Computed tomography revealed a 2-cm tumor at the tail of the pancreas. Since no other obvious distal metastases were observed, the patient underwent simultaneous surgical procedures, excising the esophageal squamous cell carcinoma and the pancreatic metastasis. A histopathological examination confirmed squamous cell carcinoma in both specimens. The patient has been free of disease for 9 months since the resection. A literature review of all relevant cases to date also demonstrated that the primary tumor site in all cases of patients with esophageal cancer presenting with metastasis to the pancreas was the lower thoracic esophagus. Complete simultaneous resections of esophageal squamous cell carcinoma and a solitary metastasis to the pancreas is beneficial and may produce favorable outcomes. However, due to the reduced number of corresponding reports, further studies are required for the confirmation of the benefits of surgery.
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Pancreatic cancer (PaCa) tends to be resistant to chemotherapy and is associated with a very poor prognosis. It has been previously reported by the authors that integrinlinked kinase (ILK) is a prognostic factor in PaCa. ILK expression was examined in a newly established gemcitabine (Gem)resistant (GemR) PaCa cell line and it was demonstrated that ILK expression was upregulated compared with that in Gemsensitive (GemS) cells. In the present study, the effects of increased ILK expression in GemR PaCa cells were evaluated and it was examined whether compound 22 (Cpd22), an ILK inhibitor, exerted antitumor effects not only in GemS cells but also in GemR cells. Reverse transcriptionquantitative polymerase chain reaction and western blotting revealed that ILK expression was higher in GemR PaCa cells than in GemS PaCa cells. Cpd22 inhibited the growth of PaCa cells in a concentrationdependent manner. Cpd22 also inhibited the growth of GemR PaCa cells. The invasive and angiogenic potential of GemR PaCa cells was enhanced compared with that in GemS cells; however, ILK small interfering RNA and Cpd22 treatment suppressed this enhancement of invasive potential compared with that in GemS cells. The addition of Cpd22 to Gem also improved the sensitivity of GemR cell lines to Gem. Furthermore, enhanced Akt signaling was associated with increased malignancy in GemR cell lines. In conclusion, ILK was upregulated with resistance and may be involved in tumor angiogenesis, invasive potential, and chemotherapy resistance, which were all suppressed by Cpd22 treatment. Thus, Cpd22 may be a novel therapeutic agent for the treatment of PaCa.
Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Regulação para Cima , Proliferação de Células , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias PancreáticasRESUMO
Girdin, an actinbinding protein, is reportedly involved in the invasion and angiogenesis of various cancers. It has been suggested that the flavonoid Scutellarin (SCU) inhibits Girdin signaling. In the present study, the function and therapeutic applications of Girdin in pancreatic cancer (PaCa) were investigated. Immunohistochemical staining of Girdin in resected PaCa specimens from the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science showed that high Girdin expression was associated with poor overall survival and relapsefree survival, as well as with T factor, indicating invasion into the surrounding tissues. On the other hand, Girdin was highly expressed in almost all PaCa cell lines, and the migration ability of Girdinknockdown cell lines was decreased even under epidermal growth factor (EGF) stimulation. In addition, SCU suppressed PaCa cell migration by inhibiting the phosphorylation of Girdin. The expression and production of vascular endothelial growth factor A (VEGFA) was significantly decreased in Girdinknockdown cell lines. Furthermore, in Matrigel tube formation assays performed using culture supernatant, the lumenforming ability of vascular endothelial cells was also decreased in Girdinknockdown cell lines. However, SCU treatment did not significantly alter the expression or production of VEGFA. These results suggested that Girdin is involved in EGF signalingmediated migration of PaCa cells, that SCU inhibits PaCa invasion by suppressing Girdin activity, and that Girdin is also involved in angiogenesis via an activation pathway different from the action site of SCU. Girdin may be a prognostic biomarker, and the development of a novel moleculartargeted drugs for Girdin may improve the prognosis of PaCa in the future.
Assuntos
Proteínas dos Microfilamentos , Neoplasias Pancreáticas , Proteínas de Transporte Vesicular , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células Endoteliais/metabolismo , Fator de Crescimento Epidérmico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismoRESUMO
Background: Inflow control is one of the most important procedures during anatomical liver resection (ALR), and Glissonean pedicle isolation (GPI) is one of the most efficacious methods used in laparoscopic anatomical liver resection (LALR). Recognition of the Laennec's capsule covering the liver parenchyma is essential for safe and precise GPI. The purpose of this study was to verify identification of the Laennec's capsule, to confirm the validity of GPI in minimally invasive surgery, and to demonstrate the value of GPI focusing on the Laennec's capsule using a robotic system that has been developed in recent years. Methods: We used a cadaveric model to simulate the Glissonean pedicle and the surrounding liver parenchyma for pathologic verification of the layers. We performed 60 LALRs and 39 robotic anatomical liver resections (RALRs) using an extrahepatic Glissonean approach, from April 2020 to April 2023, and verified the layers of the specimens removed during LALR and RALR based on pathologic examination. In addition, the surgical outcomes of LALR and RALR were compared. Results: Histologic examination facilitated by Elastica van Gieson staining revealed the presence of Laennec's capsule covering the liver parenchyma in a cadaveric model. Similar findings were obtained following LALR and RALR, thus confirming that the gap between the Glissonean pedicle and the Laennec's capsule can be dissected without injury to the parenchyma. The mean GPI time was 32.9 and 27.2 min in LALR and RALR, respectively. The mean blood loss was 289.7 and 131.6 mL in LALR and RALR, respectively. There was no significant difference in the incidence of Clavien-Dindo grade ≥III complications between the two groups. Conclusions: Laennec's capsule is the most important anatomical landmark in performing a safe and successful extrahepatic GPI. Based on this concept, it is possible for LALR and RALR to develop GPI focusing on the Laennec's capsule. Furthermore, a robotic system has the potential to increase the safety and decrease the difficulty of this challenging procedure.
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An-81-year-old man presented to another doctor complaining of epigastric pain. He was referred to us after the laboratory data revealed a high serum CEA and abdominal ultrasonography showed the space occupying lesion in the left liver. Abdominal CT revealed advanced gallbladder cancer infiltrating the liver and colon and found annular pancreas surrounding the descending portion of duodenum. We chose partial hepatectomy(S4a+S5), extrahepatic bile duct resection with hepaticojejunostomy and partial colectomy. Pathological diagnosis of the tumor was pT3N1M0, gallbladder cancer. The patient was discharged on the 21 days after operation. The frequency of malignant tumors in adult annular pancreas are not revealed. But some cases present with adult annular pancreas complicating the biliary tract tumor. We experienced a case of advanced gallbladder cancer with adult annular pancreas and report our case and review the pertinent literature.
Assuntos
Neoplasias da Vesícula Biliar , Pancreatopatias , Masculino , Humanos , Adulto , Neoplasias da Vesícula Biliar/patologia , Pâncreas/patologia , Pancreatopatias/cirurgia , Fígado/patologiaRESUMO
BACKGROUND: Neuroendocrine tumors of the minor papilla are very rare, and only 20 cases have been reported in the literature. Neuroendocrine carcinoma of the minor papilla with pancreas divisum has not been reported previously, making this the first reported case. Neuroendocrine tumors of the minor papilla have been reported in association with pancreas divisum in about 50% of cases reported in the literature. We herein present our case of neuroendocrine carcinoma of the minor papilla with pancreas divisum in a 75-year-old male with a systematic literature review of the previous 20 reports of neuroendocrine tumors of the minor papilla. CASE PRESENTATION: A 75-year-old Asian man was referred to our hospital for evaluation of dilation of the main pancreatic duct noted on abdominal ultrasonography. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed a dilated dorsal pancreatic duct, which was not connected to the ventral pancreatic duct; however, it opened to the minor papilla, indicating pancreas divisum. The common bile duct had no communication with the pancreatic main duct and opened to the ampulla of Vater. A contrast-enhanced computed tomography scan showed a 12-mm hypervascular mass near the ampulla of Vater. Endoscopic ultrasonography showed a defined hypoechoic mass in the minor papilla with no invasion. The biopsies performed at the previous hospital found adenocarcinoma. The patient underwent a subtotal stomach-preserving pancreaticoduodenectomy. The pathological diagnosis was neuroendocrine carcinoma. At the 15-year follow-up visit, the patient was doing well with no evidence of tumor recurrence. CONCLUSION: In our case, because the tumor was discovered during a medical check-up relatively early in the course of disease, the patient was doing well at the 15-year follow-up visit, with no evidence of tumor recurrence. Diagnosing a tumor of the minor papilla is very difficult because of the relatively small size and submucosal location. Carcinoids and endocrine cell micronests in the minor papilla occur more frequently than generally thought. It is very important to include neuroendocrine tumors of the minor papilla in the differential diagnosis of patients with recurrent pancreatitis or pancreatitis of unknown cause, especially for patients with pancreas divisum.
Assuntos
Carcinoma Neuroendócrino , Pâncreas Divisum , Pancreatite , Masculino , Humanos , Idoso , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Recidiva Local de Neoplasia/patologia , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Colangiopancreatografia Retrógrada Endoscópica , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/cirurgiaRESUMO
A 35-year-old man who had fever and stomachache was referred to our hospital. He underwent surgery and chemoradiotherapy for neuroblastoma as a child and subsequently developed leukemia. Frequent blood transfusions and bone marrow transplants were performed due to anemia. Abdominal contrast CT scan and contrast MRI showed tumorous lesions with a diameter of 60×42 mm in liver S6, and a tendency to increase in a short term. There was also hemochromatosis in the liver. We considered it a malignant tumor and performed a right lobectomy. Pathological examination diagnosed the tumor hepatic angiosarcoma. The postoperative course was fine and he was discharged without complications. But multiple liver metastases appeared 6 months after surgery. We performed chemotherapy but he passed away 10 months after surgery. Hepatic angiosarcoma is a rare disease among liver malignancies and has a very poor prognosis. As for the cause of hepatic angiosarcoma, many of them are unknown, but chronic exposures such as vinyl monomers have been reported in some cases. Hemochromatosis has been reported as a background factor for malignant tumors such as hepatocellular carcinoma. In this case it is possible that it contributed to the development of hepatic angiosarcoma.
Assuntos
Carcinoma Hepatocelular , Hemangiossarcoma , Hemocromatose , Neoplasias Hepáticas , Masculino , Criança , Humanos , Adulto , Hemocromatose/complicações , Hemangiossarcoma/cirurgia , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/complicaçõesRESUMO
INTRODUCTION: Ischemic gastropathy is one of the unique postoperative complications associated with distal pancreatectomy with celiac axis resection for locally advanced pancreatic cancer. Therefore, it is essential to evaluate blood flow to the stomach following a resection; however, no intraoperative procedures have been established to assess this issue. Herein we describe two cases in which intraoperative evaluation of real-time blood flow in the residual stomach was performed using indocyanine green fluorescence and da Vinci Firefly technology during a robot-assisted distal pancreatectomy with celiac axis resection. METHODS: Robot-assisted distal pancreatectomy with celiac axis resection was performed using a da Vinci Xi surgical system on two patients with locally advanced pancreatic cancer and suspected invasion of the celiac artery. Indocyanine green (ICG) (0.5 mg/kg) was injected intravenously after resection to evaluate real-time blood flow of the stomach using the da Vinci Firefly system. Blood flow of the stomach was evaluated 60 seconds after the intravenous injection of ICG. RESULTS: All cases were confirmed that there was sufficient blood flow in the residual stomach. Therefore, reconstruction of the left gastric artery was not performed, and the surgery was completed with preservation of the stomach. Good postoperative outcomes were achieved and there was no evidence of ischemic gastropathy or delayed gastric emptying in both cases. CONCLUSION: This method is very useful in determining whether or not to perform reconstruction of the left gastric artery and/or additional resection of the remnant stomach during a robot-assisted distal pancreatectomy with celiac axis resection.
Assuntos
Coto Gástrico , Neoplasias Pancreáticas , Robótica , Humanos , Animais , Coto Gástrico/cirurgia , Artéria Celíaca/diagnóstico por imagem , Artéria Celíaca/cirurgia , Verde de Indocianina , Vaga-Lumes , Pancreatectomia/efeitos adversos , Isquemia/etiologia , Isquemia/cirurgia , Neoplasias Pancreáticas/cirurgia , Imagem ÓpticaRESUMO
OBJECTIVE: The aim of this study is to evaluate the utility of adjuvant radiotherapy (intraoperative radiotherapy, IORT; postoperative radiotherapy, PORT), and definitive radiotherapy for non-metastatic pancreatic cancer. METHODS: Ninety-nine patients were analyzed. Thirty patients underwent IORT with surgery, 31 underwent PORT after surgery, and 38 underwent definitive radiotherapy. Tumor stage [Union for International Cancer Control (UICC) 2009] was as follows: Stage I, 7; IIA, 16; IIB, 31; III, 45. The doses for IORT, PORT, and definitive radio therapy were 20 to 30, 40 to 64.6, and 50.4 to 61.2 Gy, respectively. Associations between clinical parameters including age, gender, tumor site, stage, performance status, surgical margin, and use of chemotherapy and local control (LC) or overall survival (OS) were analyzed. RESULTS: Follow-up periods for all patients were 1.1-145 months (median, 11). OS rate in the IORT, PORT, and definitive radiotherapy groups was 22%, 16%, and 6%, respectively, at 2 years. The 5-year OS rate was 13%, 3.2%, and 0%, respectively. Local control rate at 2 years was 33%, 35%, and 0%, respectively. No Grade ≥ 3 tox icities were observed. Distant metastasis was less common in the IORT group. Stage and surgical margin were sig nificant factors for OS after IORT. Performance status and chemotherapy were significant factors for OS after PORT and definitive radiotherapy. CONCLUSIONS: The present study showed the safety of the three treatment modalities, but the outcomes were not satisfactory. More intensive strategies including radiotherapy should be investigated.
Assuntos
Neoplasias Pancreáticas , Humanos , Terapia Combinada , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/tratamento farmacológico , Margens de Excisão , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
The patient described herein was diagnosed with left breast, endometrial, and early gastric cancers at 49, 53, and 57 years of age, respectively. Magnetic resonance cholangiopancreatography performed when she was undergoing treatment for cholecystitis at 50 years of age showed local pancreatic duct dilatation in the pancreatic head. She was followed in the Department of Gastroenterology at our hospital for an intraductal papillary mucinous neoplasm(IPMN). An abdominal computed tomography scan obtained at 59 years of age revealed dilation of the main pancreatic duct in the pancreas body and tail, therefore an endoscopic ultrasound-guided fine needle aspiration was performed. She was diagnosed with pancreatic cancer and underwent a laparoscopic distal pancreatectomy. The postoperative course was uneventful; however, the pancreatic cancer recurred and she died approximately 14 months postoperatively. Reports of multiple cancers associated with IPMNs are rare, yet we managed a patient with a pancreatic head IPMN complicated by metachronous quadruple carcinomas( breast, endometrial, gastric, and pancreatic cancers).
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Feminino , Humanos , Carcinoma Ductal Pancreático/patologia , Neoplasias Intraductais Pancreáticas/cirurgia , Pancreatectomia , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pancreáticas/patologia , Ductos Pancreáticos/patologiaRESUMO
Pancreatic cancer (PaCa) exhibits one of the poorest prognoses among all gastrointestinal cancers due to the rapid development of treatment resistance, which renders chemotherapy and radiotherapy no longer effective. However, the mechanisms through which PaCa becomes resistant to radiotherapy are unknown. Here, we established radiationresistant PaCa cell lines to investigate the factors involved in radiation resistance. The role of the CXC motif chemokine ligand 12 (CXCL12)/CXC chemokine receptor type 4 (CXCR4) axis in radiation resistance in PaCa and the effects of a CXCR4 antagonist on radiationresistant PaCa cell lines were investigated. As confirmed by immunofluorescence staining, reverse transcription quantitative polymerase chain reaction, and western blotting, the expression of CXCR4 was higher in radiationresistant PaCa cell lines than that noted in normal PaCa cell lines. The invasion ability of radiationresistant PaCa cell lines was greater than that of normal cell lines and was enhanced by CXCL12 treatment and coculture with fibroblasts; this enhanced invasion ability was suppressed by the CXCR4 antagonist AMD070. Irradiation after treatment with the CXCR4 antagonist suppressed the colonization of radiationresistant PaCa cell lines. In conclusion, the CXCL12/CXCR4 axis may be involved in the radiation resistance of PaCa. These findings may facilitate the development of novel treatments for PaCa.
Assuntos
Quimiocina CXCL12 , Neoplasias Pancreáticas , Receptores CXCR4 , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocina CXCL12/genética , Fibroblastos , Humanos , Pâncreas , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/radioterapia , Tolerância a Radiação , Receptores CXCR4/genética , Transdução de SinaisRESUMO
10ZHymenialdisine is a natural product derived from the marine sponge Axinella carteri. 10ZHymenialdisine has antiinflammatory effects exerted through NFκB; however, it is unclear whether 10ZHymenialdisine has antiangiogenic effects in cancer cells. In the present study, both the antiangiogenic and antimetastatic effects of this compound in pancreatic cancer were investigated. It was initially confirmed that 10ZHymenialdisine significantly inhibited the proliferation of pancreatic cancer cells. Next, using both reverse transcriptionquantitative PCR and ELISA, it was demonstrated that 10ZHymenialdisine significantly suppressed the expression of VEGF and IL8 mRNAs and proteins in pancreatic cancer. Immunohistochemical analysis revealed that 10ZHymenialdisine inhibited NFκB activity in pancreatic cancer cell lines. It was also identified that 10ZHymenialdisine inhibited tube formation in EA.hy926 cells. In vivo, 10ZHymenialdisine significantly inhibited the growth of BxPC3 pancreatic cancer cells that were subcutaneously injected into model mice. In conclusion, the present study demonstrated that 10ZHymenialdisine exerted antiangiogenic effects by suppressing NFκB activity and angiogenic factors, such as VEGF and IL8, in pancreatic cancer cell lines. 10ZHymenialdisine has potential applications as a novel therapeutic agent for the treatment of pancreatic cancer.
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Inibidores da Angiogênese/farmacologia , Azepinas/farmacologia , NF-kappa B/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Pirróis/farmacologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Camundongos , Neovascularização PatológicaRESUMO
Pancreatic cancer (PaCa) is one of the most aggressive types of cancer. Thus, the development of new and more effective therapies is urgently required. Escin, a pentacyclic triterpenoid from the horse chestnut, has been reported to exhibit antitumor potential by reducing cell proliferation and blocking the nuclear factorκB (NFκB) signaling pathway in several types of cancer. Our previous study reported that NFκB enhanced the secretion of interleukin (IL)8 and vascular endothelial growth factor (VEGF), thereby inducing angiogenesis in PaCa cell lines. In the present study, it was examined whether escin inhibited angiogenesis by blocking NFκB activation in PaCa. It was initially confirmed that escin, at concentrations >10 µM, significantly inhibited the proliferation of several PaCa cell lines. Next, using immunocytochemical staining, it was found that escin inhibited the nuclear translocation of NFκB. Furthermore, ELISA confirmed that NFκB activity in the escintreated PaCa cells was significantly inhibited and reverse transcriptionquantitative PCR showed that the mRNA expression levels of tumor necrosis factorαinduced IL8 and VEGF were significantly suppressed following escin treatment in the PaCa cell lines. ELISA also showed that escin decreased the secretion of IL8 and VEGF from the PaCa cells. Furthermore, tube formation in immortalized human endothelial cells was inhibited following incubation with the supernatants from escintreated PaCa cells. These results indicated that escin inhibited angiogenesis by reducing the secretion of IL8 and VEGF by blocking NFκB activity in PaCa. In conclusion, escin could be used as a novel molecular therapy for PaCa.
Assuntos
Escina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Fator de Transcrição RelA/antagonistas & inibidores , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Escina/uso terapêutico , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fator de Transcrição RelA/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
We experienced a case of solitary liver tumor that developed after renal cancer surgery. Before the surgery, the tumor was suspected to be hepatocellular carcinoma and was subsequently diagnosed as renal cancer liver metastasis. An 81-year-old man underwent retroperitoneal laparoscopic nephrectomy for left renal cancer in January 2017. After that, the cancer had not recurred, but a follow-up CT examination 1 year after the operation revealed a 42 mm-sized tumor in the liver S6. Liver biopsy was performed for diagnosis, but in histopathological findings, the diagnosis was difficult to make. Eventually, the preoperative final diagnosis was hepatocellular carcinoma. Laparoscopic partial hepatectomy was performed in June 2018, and in the histopathological findings of the resected specimen, the final diagnosis was the liver metastasis from renal cancer. Generally, the prognosis of renal cancer with liver metastasis is poor, but if complete resection is possible, it is recommended in the Clinical Practical Guideline for Renal Cancer. In recent years, the number of minimally invasive laparoscopic surgeries for hepatectomy has increased, and its safety has also improved. Therefore, resection is diagnostic treatment for cases where, like this case, preoperative diagnosis for solitary liver tumor is difficult. Laparoscopic hepatectomy could be one of the effective treatment strategies.
Assuntos
Carcinoma Hepatocelular , Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Neoplasias Hepáticas , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Carcinoma de Células Renais/cirurgia , Hepatectomia , Humanos , Neoplasias Renais/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: An epithelial cyst in an intrapancreatic accessory spleen (ECIPAS) is rare. We report a case of ECIPAS that was treated with robot-assisted distal pancreatectomy with splenectomy. CASE PRESENTATION: The case was a 59-year-old woman who was referred to our hospital after a pancreatic tail tumor was found on computed tomography prior to surgery for small bowel obstruction at another hospital. A cystic lesion in the pancreatic tail was discovered and evaluated by magnetic resonance imaging and endoscopic ultrasonography. Based on clinical and radiological features, mucinous cystic neoplasm was included in the differential diagnosis. The patient underwent robot-assisted distal pancreatectomy with splenectomy. The postoperative course was uneventful. Pathological evaluation revealed a 20-mm ECIPAS in the pancreatic tail. CONCLUSIONS: If a pancreatic tail tumor is present, ECIPAS should be included in the differential diagnosis. However, preoperative diagnosis is difficult, and a definitive diagnosis is often not obtained until after surgery. Surgery should be minimally invasive. Laparoscopic distal pancreatectomy has become a standard surgical procedure because it is minimally invasive. Robot-assisted surgery is not only minimally invasive, but also advantageous, because it has a stereoscopic magnifying effect and allows the forceps to move smoothly. Robot-assisted distal pancreatectomy may be a good option, when performing surgery for a pancreatic tail tumor.
Assuntos
Coristoma , Cisto Epidérmico , Pancreatopatias , Procedimentos Cirúrgicos Robóticos , Baço , Esplenopatias , Idoso , Coristoma/diagnóstico por imagem , Endossonografia , Cisto Epidérmico/diagnóstico por imagem , Cisto Epidérmico/cirurgia , Feminino , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Pancreatectomia , Pancreatopatias/diagnóstico por imagem , Pancreatopatias/cirurgia , Baço/diagnóstico por imagem , Baço/cirurgia , Esplenectomia , Esplenopatias/diagnóstico por imagem , Esplenopatias/cirurgia , Tomografia Computadorizada por Raios XRESUMO
A 60's man came to our hospital for jaundice. Contrast-enhanced CT showed irregular thickening of the hilar bile duct, and the lymph nodes(LN)were swollen from the hilar to the abdominal aorta. These LNs showed similar findings in endoscopic ultrasonography(EUS), and fine needle aspiration cytology(FNA)was performed on the enlarged No.13LN to diagnose LN metastasis of hilar cholangiocarcinoma. Since the peri-aortic LN was also markedly enlarged, it was considered to be metastasis, and was diagnosed as unresectable hilar cholangiocarcinoma with distant LN metastasis. When gemcitabine/cisplatin therapy(GC therapy)was started, tumor markers normalized and LN decreased in 4 months. We performed GC therapy for a total of 12 cycles and did not re-exacerbate. Cholangioscopy revealed that bile duct stenosis at the hilar portion had improved. We have determined that curative resection is possible and performed surgery. We confirmed that No.16b1LN was negative by pathological diagnosis during surgery and performed left hepatic caudate lobectomy, extrahepatic cholangectomy, and biliary reconstruction. Diagnosis was pT2aN1(n8a)M0, fStage â ¢B, and pR0. After surgery, adjuvant chemotherapy with S-1 was continued.
Assuntos
Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Tumor de Klatskin , Terapia Neoadjuvante , Hepatectomia , Humanos , MasculinoRESUMO
The case is a 59-year-old woman. A medical examination revealed a high CA19-9, she visited a nearby hospital. Abdominal echo showed thickening of the gallbladder wall, and she was referred to our hospital for further examination. EUS-FNA was performed and a biopsy of #12 lymph node revealed undifferentiated cancer, which was diagnosed as gallbladder cancer. FDG-PET showed accumulation of FDG in the gallbladder lumen and swollen lymph nodes around the aorta. Therefore, the cancer was considered unresectable and chemotherapy was performed. FDG-PET was re-examined after 4 courses of gemcitabine plus cisplatin combination chemotherapy. As a result, the lymph node swelling contracted, the accumulation of FDG disappeared, and surgery was scheduled. Extended cholecystectomy and extrahepatic bile duct resection were performed. She was discharged 22 days after the surgery without complications. Histopathological examination showed fibrotic tissue at the gallbladder and lymph nodes, but no residual tumor cells. There are no recurrences 11 months after surgery. Although the prognosis of gallbladder cancer with para-aortic lymph node metastasis is generally poor, it is suggested that conversion surgery with multimodality treatment including preoperative chemotherapy may be a useful therapeutic strategy.