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5-Fluorouracil (5-FU) is widely used in gastric cancer treatment, yet 5-FU resistance remains an important clinical challenge. We established a model based on five long noncoding RNAs (lncRNA) to effectively assess the prognosis of gastric cancer patients; among them, lncRNA OVAAL was markedly upregulated in gastric cancer and associated with poor prognosis and 5-FU resistance. In vitro and in vivo assays confirmed that OVAAL promoted proliferation and 5-FU resistance of gastric cancer cells. Mechanistically, OVAAL bound with pyruvate carboxylase (PC) and stabilized PC from HSC70/CHIP-mediated ubiquitination and degradation. OVAAL knockdown reduced intracellular levels of oxaloacetate and aspartate, and the subsequent pyrimidine synthesis, which could be rescued by PC overexpression. Moreover, OVAAL knockdown increased sensitivity to 5-FU treatment, which could be reversed by PC overexpression or repletion of oxaloacetate, aspartate, or uridine. OVAAL overexpression enhanced pyrimidine synthesis to promote proliferation and 5-FU resistance of gastric cancer cells, which could be abolished by PC knockdown. Thus, OVAAL promoted gastric cancer cell proliferation and induced 5-FU resistance by enhancing pyrimidine biosynthesis to antagonize 5-FU induced thymidylate synthase dysfunction. Targeting OVAAL-mediated nucleotide metabolic reprograming would be a promising strategy to overcome chemoresistance in gastric cancer.
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RNA Longo não Codificante , Neoplasias Gástricas , Ácido Aspártico/farmacologia , Ácido Aspártico/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Nucleotídeos/farmacologia , Nucleotídeos/uso terapêutico , Oxaloacetatos/farmacologia , Oxaloacetatos/uso terapêutico , Piruvato Carboxilase/genética , RNA Longo não Codificante/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
Doxorubicin (Dox) is an effective chemotherapy drug against a wide range of cancers, including both hematological and solid tumors. However, the serious cardiotoxic effect restricted its clinical application. We previously have illuminated the protective role of canonical Wnt/ß-catenin signaling in Dox-induced cardiotoxicity. Secreted frizzled-related protein 1 (sFRP1) is one of the endogenous inhibitors of both canonical and noncanonical Wnt signaling. In this study, we investigated the relationship between sFRP1 and noncanonical Wnt/PCP-JNK (Wnt/planar cell polarity-c-Jun N-terminal kinase) pathway in Dox-induced cardiotoxicity in vitro and in vivo. We showed that treatment of H9c2 cardiac myoblasts with Dox (1 µM) time-dependently suppressed cell viability accompanied by significantly decreased sFRP1 protein level and increased Wnt/PCP-JNK signaling. Pretreatment with SP600125, the Wnt/PCP-JNK signaling inhibitor, attenuated Dox-induced apoptosis of H9c2 cells. Overexpression of sFRP1 protected H9c2 cells from Dox-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway. After intraperitoneal injection of a cumulative dose of 15 mg/kg Dox, rats displayed significant cardiac dysfunction; their heart showed inhibited Wnt/ß-catenin signaling and activated Wnt/PCP-JNK signaling. These results suggest that sFRP1 may be a novel target for Dox-induced cardiotoxicity.
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Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Cardiotoxicidade/metabolismo , Doxorrubicina/efeitos adversos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , Via de Sinalização Wnt/fisiologia , Animais , Antracenos/farmacologia , Linhagem Celular , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Ratos Sprague-Dawley , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
The function of metformin in colorectal cancer (CRC) patients with diabetes mellitus (DM) remains a controversial topic because studies are increasingly focusing on epidemiologic features. We examined Notch1/Hes1 signaling in CRC with DM (DM-CRC) and investigated alterations in signaling caused by metformin treatment. For this purpose, information on pathological characteristics was collected from each patient. The proliferation of epithelium labeled with proliferating cell nuclear antigen and the differentiation of goblet cells were investigated using immunohistochemistry and periodic acid-Schiff staining, respectively. The factors involved in Notch1/Hes1 signaling were detected using qRT-PCR and western blot. In our study, we found that lymphatic metastasis, pTNM staging, and the carcinoembryonic antigen level were significantly different between groups. The depth of crypts and the rate of proliferating cell nuclear antigen-positive cells were distinctly higher in DM-CRC and patients who were managed with insulin. Moreover, the goblet cell differentiation rate was decreased in DM-CRC. The expression of Dll1, Notch1, Math1, and RBP-Jκ was increased in DM-CRC, whereas the expression of Dll4 and Hes1 was decreased in this group in normal tissue. In CRC tissue, the expression of Dll1 and Notch1 was clearly higher than that in DM-CRC. Furthermore, the trend in these changes was aggravated with insulin management and alleviated with metformin treatment. In conclusion, the abnormal cell proliferation and differentiation observed in DM-CRC are correlated with overactivated Notch1/Hes1 signaling, which is potentially relieved by metformin treatment.
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Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Receptor Notch1/metabolismo , Fatores de Transcrição HES-1/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Humanos , Insulina/uso terapêutico , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To explore the interfering effects of siRNA on endogenous VEGF-C genes and the protein expression in gastric cancer cells. METHODS: Cultured gastric cancer cell line SGC7901 cells were prepared in vitro. Five siRNA primers of VEGF-C were designed depending on the sequence of Accession No. BC035212. 1 in Genbank. After homology analysis, the primers were synthesized and transfected into SGC7901 cells. The endogenous VEGF-C mRNA level and its protein expression were observed. RESULTS: VEGF-C-siRNA was inserted into the gastric cancer cell successfully. Five siRNA primers of VEGF-C could inhibit VEGF-C genes and protein expression. CONCLUSION: siRNA could block the endogenous VEGF-C genes and the protein expression in gastric cancer cell.
Assuntos
RNA Interferente Pequeno/genética , Neoplasias Gástricas/genética , Fator C de Crescimento do Endotélio Vascular/genética , Linhagem Celular Tumoral , Humanos , Interferência de RNA , Neoplasias Gástricas/patologia , TransfecçãoRESUMO
Background: Colorectal cancer (CRC) is a common malignant tumor that affects the large bowel or the rectum. Cuproptosis, recently discovered programmed cell death process, may play an important role in CRC tumorigenesis. Long non-coding RNAs (lncRNAs) can alter the proliferation of colorectal cancer cells through the control and activation of gene expression. To date, cuproptosis-related lncRNAs, have not been investigated as potential predictive biomarkers in colorectal cancer. Methods: The mRNA and lncRNA expression data of colorectal cancer were gathered from The Tumor Genome Atlas (TCGA) database, and Pearson correlation analysis and univariate Cox regression analysis were used to identify the lncRNAs with differential prognosis. Colorectal cancer was classified using consistent clustering, and the clinical significance of different types, tumor heterogeneity, and immune microenvironment differences was investigated. The differential lncRNAs were further screened using LASSO regression to develop a risk scoring model, which was then paired with clinicopathological variables to create a nomogram. Finally, the copy number changes in the high-risk and low-risk groups were compared. Results: Two clusters were formed based on the 28 prognostic cuproptosis-related lncRNAs, and the prognosis of cluster 2 was found to be significantly lower than that of cluster 1. Cluster 1 showed increased immune cell infiltration and immunological score, as well as strong enrichment of immune checkpoint genes. Next, LASSO regression was used to select 11 distinctive lncRNAs, and a risk score model was constructed using the training set to distinguish between high and low-risk groups. Patients in the high-risk group had a lower survival rate than those in the low-risk group, and both the test set and the total set produced consistent results. The AUC value of the ROC curve revealed the scoring model's efficacy in predicting long-term OS in patients. Moreover, the model could be used as an independent predictor when combined with a multivariate analysis of clinicopathological features, and our nomogram could be used intuitively to predict prognosis. Conclusion: Collectively, we developed a risk model using 11 differential lncRNAs and demonstrated that the model has predictive value as well as clinical and therapeutic implications for predicting prognosis in CRC patients.
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Many studies reported that long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) metastasis and tumorigenesis. However, the underlying mechanisms of lncRNAs in GC remain unexplored to a great extent. LINC01537 expression level was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Its biological roles in GC were then investigated using functional experiments. In order to investigate the underlying mechanism of LINC01537 in GC, RNA pull-down, RNA immunoprecipitation, and ubiquitination assays were performed. LINC01537 was significantly overexpressed in GC tissues and associated with a poor prognosis. Functional experimental results revealed that LINC01537 promoted the proliferation, invasion, and migration of GC cells. The animal experiments revealed that LINC01537 promoted tumorigenesis and metastasis in vivo. Mechanistically, LINC01537 stabilizes RIPK4 by reducing the binding of RIPK4 to TRIM25 and reducing its ubiquitination degradation, thereby promoting the expression of the NF-κB signaling pathway. According to our findings, the LINC01537-RIPK4-NF-κB axis promoted GC metastasis and tumorigenesis.
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Laparoscopic total mesorectal excision (TME) with autonomic nerve preservation (ANP) is a common procedure for rectal cancer (RC), associated with a high prevalence of postoperative urogenital and anorectal dysfunctions. Compared to 2D laparoscopy, 3D laparoscopy provides better depth perception of the surgical field and hand-eye coordination to achieve better outcomes. We compared the performance of 2D and 3D laparoscopy on preserving urogenital and anorectal function in TME+ANP surgery for rectal cancer using propensity-score matching. Data were collected from consecutive male patients who underwent 3D or 2D laparoscopic TME+ANP for primary RC at our institution between March 2012 and December 2020. The primary outcome was sexual and urinary function 1 year after surgery. A total of 450 male patients were eligible. After 1:1 matching, 146 cases were included in each group for analysis. One year after surgery, the prevalence of sexual dysfunction (International Index of Erectile Function score <26) was 8.22% in the 3D laparoscopic group and 44.52% in the 2D laparoscopic group, respectively (P=0.000) and a significant difference in the incidence of urinary retention was observed (n=3 and 24, respectively (P=0.000)). Moreover, blood loss, operative time, duration of hospital stay, and the time to first flatus in the 3D laparoscopic group were significantly less than in the 2D laparoscopic group. In conclusion, 3D laparoscopic TME is associated with lower incidences of postoperative sexual and urinary dysfunction than 2D laparoscopic TME for rectal cancer in male patients.
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OBJECTIVE: To compare the clinical outcomes of laparoscopic-assisted versus hand-assisted laparoscopic radical operations in colorectal cancer and evaluate the safety and indications of hand-assisted laparoscopic operations. METHODS: A total of 64 consecutive colorectal cancer patients enrolled from November 2009 to December 2011 at our hospital were randomly and prospectively divided into 2 groups: hand-assisted laparoscopic operation (HALS) (n = 32) and laparoscopic-assisted operation (n = 32). And such clinicopathologic features as safety, operative curability and postoperative recovery were compared between two groups. RESULTS: Neither death nor conversion-to-open-surgery was reported among all patients. There were no statistical differences in such clinicopathologic features as age, gender, body mass index, mass size and location (all P > 0.05). There were statistically a shorter operation time [(127 ± 31) min vs (184 ± 71) min, P = 0.022] and a smaller number of Trocar (2.4 vs 5.0, P = 0.015) in the HALS group. However, the laparoscopic-assisted group had a lesser volume of blood loss [(82 ± 31) ml vs (150 ± 42) ml, P = 0.008] and a smaller postoperative 48 h drainage flow [(170 ± 52) ml vs (208 ± 58) ml, P = 0.020]. Moreover, no statistical differences existed in the length of bowel resection [(19 ± 5) cm vs (18 ± 4) cm], amount of lymph nodes dissection (16 ± 4 vs 16 ± 3), postoperative complications [12.5% (4/32) vs 25.0% (8/32)], time of intestinal function recovery [(1.7 ± 0.9) d vs (1.8 ± 0.7) d], time of semifluid tolerance [(2.9 ± 1.3) vs (2.8 ± 1.2) d], hospitalization expenses [(4.8 ± 0.6) 10 000 yuan vs (4.9 ± 0.4) 10 000 yuan] and postoperative hospital stay [(6.7 ± 2.3) d vs (6.6 ± 2.3) d] (all P > 0.05). CONCLUSION: HALS is both safe and efficacious for colorectal cancer patients.
Assuntos
Colectomia , Laparoscopia Assistida com a Mão , Neoplasias Colorretais/cirurgia , Humanos , Laparoscopia , Estudos RetrospectivosRESUMO
At present, natural orifice specimen extraction surgery (NOSES) has attracted more and more attention worldwide, because of its great advantages including minimal cutaneous trauma and post-operative pain, fast post-operative recovery, short hospital stay, and positive psychological impact. However, NOSES for the treatment of gastric cancer (GC) is still in its infancy, and there is great potential to improve its theoretical system and clinical practice. Especially, several key points including oncological outcomes, bacteriological concerns, indication selection, and standardized surgical procedures are raised with this innovative technique. Therefore, it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES, which is of great significance for healthy and orderly development of NOSES worldwide.
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OBJECTIVE: To evaluate and compare the results of vagina vasorum lymph node dissection (VLND) and non-vagina vasorum lymph node dissection (NVLND) in patients with gastric cancer after radical operation. METHODS: A total of 759 cases of evaluable patients with gastric cancer, operated from June 1994 to April 2005, were retrospectively analyzed. Of which, 627 cases underwent radical gastrectomy: 215 patients received VLND and 412 cases received NVLND. The operation time, intraoperative blood loss, operative complications and survival rate were recorded and compared between the two groups. RESULTS: The 5- and 10-year overall accumulative survival rates of VLND group and NVLND group were 55.4% and 51.2%, 39.1%and 36.8%, respectively (all P < 0.05). No significant differences in intraoperative blood transfusion (loss), operation time, operative complication rate was found between the two groups. The 5- and 10-year accumulative survival in patients with a tumor of phase N0-N2, T2-T4, Ib-IV in VLND groups were all significant higher than those in NVLND group. CONCLUSIONS: VLND is a safe technique in advanced gastric cancer, it dose not prolong operation time or increase operative complications but improves survival.
Assuntos
Excisão de Linfonodo/métodos , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastrectomia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Comparison of transanal specimen extraction (TSE) and transabdominal specimen extraction (TASE) in laparoscopic rectal surgery is still sparsely reported. Trauma, pain, scarring, and bad psychological suggestion have long been considered an inevitable outcome of surgery. For laparoscopic rectal cancer surgery, whether TSE or TASE is beneficial in terms of technical platforms, indications, contraindications, technical requirements for aseptic operation, tumor-free operation, prevention and treatment of complications still has not reached a unified consensus and standards. Recently, comparison of TSE and TASE in laparoscopic rectal surgery has still been sparsely reported. AIM: In this study, we retrospectively analyzed the short-term outcomes of TSE and TASE in laparoscopic rectal surgery in a single institution in southern China. MATERIAL AND METHODS: Patients who underwent laparoscopic radical rectal cancer surgery using either TSE or TASE were recruited. Data, including patient demographics, perioperative and postoperative variables, were analyzed retrospectively. RESULTS: Sixty-seven patients were included in this study. Thirty patients underwent TSE and 37 patients underwent TASE. The two groups were similar in demographics and tumor characteristics. Postoperative complications were similar in both groups, except that wound infection was lower for the TSE group (p = 0.122). The TSE group had a better cosmetic result with no abdominal incision and no differences in circumferential margins, distal resection margins or completeness of total mesorectal excision. CONCLUSIONS: Laparoscopic TSE is recommended in the treatment of rectal cancer with similar oncologic outcomes compared with conventional TASE. It is mini-invasive surgery and has the advantage of better cosmetic results. There is a need for further randomized studies to refine the applicability of laparoscopic TSE in rectal cancer.
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BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is closely related with the progression of cancer in humans. The functional and regulatory roles of lncRNAs in colorectal cancer (CRC) are still largely unclear. The purpose of this study is to explore the function of lncRNA STARD13-AS in CRC. METHODS: The bioinformatics tool "GEPIA" was used to predict the potential expression of STARD13-AS in CRC. qRT-PCR was used to evaluate the relative expression level of STARD13-AS in CRC cells lines and tissues samples. The functional involvement of STARD13-AS in the CRC cells was assessed using MTT assay, ï¬ow cytometry, and Transwell assay. The expression levels of cyclin D, cyclin E, E-cadherin, N-cadherin, and vimentin were assessed using Western blot. RESULTS: Bioinformatics prediction and qRT-PCR results showed that STARD13-AS expression was decreased in CRC tissues. Patients with low STARD13-AS expression exhibited distant and lymphatic metastasis as well as enhancement in tumor size. STARD13-AS expression was downregulated in CRC cell lines compared to normal human colon mucosal epithelial cell line NCM460 and STARD13-AS expression in SW620 and LoVo cell lines was lowest. Moreover, we observed that while STARD13-AS overexpression suppressed the cell cycle, proliferation, migration, and invasion, while promoted apoptosis both in LoVo and SW620 cells. In addition, STARD13-AS overexpression inhibited Cyclin E, Cyclin D, N-cadherin and vimentin expression, and promoted E-cadherin expression both in LoVo and SW620 cells. CONCLUSION: Expression of STARD13-AS suppresses cell proliferation and metastasis in CRC, suggesting that STARD13-AS might act as a potential target for CRC treatment.
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OBJECTIVE: To assess the value of perforin mRNA and granzyme B mRNA in lymphocytes as an early diagnostic indicator for acute rejection of pancreatic transplantation. METHODS: Twenty-four hybrid landraces were divided into three groups (control group, transplantation group, transplantation plus immunosuppressant group) randomly. The landraces in the transplantation group were treated with pancreatoduodenal allotranplantation. The landraces in the transplantation plus immunosuppressant group underwent the same surgery and were intervened simultaneously with CsA, MMF, and Metrisone. Peripheral venous bloods were sampled via subclavic veins one day before the operations and on the 1st, 3rd, 5th and 7th day after the operations. The RNA was extracted from the blood samples. The mRNA of perforin and granzyme B expressed in the lymphocytes were detected by RT-PCR. The serum glucose, insulin and glucagons were also measured with routine methods. The pancreatic graft tissues were collected for pathologic examinations at the 1st, 3rd, 5th and 7th day after the operations. RESULTS: No differences in serum glucose, insulin and glucagons had been detected among the three groups (P>0.05). The landraces in the transplantation plus immunosuppressant group had significantly lower expression of the mRNA of perforin and granzyme B in the lymphocytes and the local transplanted pancreas than those in the transplantation group (P<0.05). The change of mRNA expression of perforin and granzyme B in the lymphocytes occurred 2-4 days earlier than the pathological changes when the acute rejection started. CONCLUSION: Monitoring the change of mRNA expression of perforin and granzyme B in the lymphocytes from the peripheral blood can help the early diagnosis of acute rejection of pancreatic transplantation.
Assuntos
Rejeição de Enxerto/sangue , Rejeição de Enxerto/diagnóstico , Granzimas/sangue , Transplante de Pâncreas/efeitos adversos , Perforina/sangue , Animais , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Granzimas/genética , Granzimas/metabolismo , Masculino , Perforina/genética , Perforina/metabolismo , RNA Mensageiro/sangue , RNA Mensageiro/genética , SuínosRESUMO
BACKGROUND: The immunological benefits of portal venous drainage (PVD) in pancreas transplantation remain debated clinically. We established simultaneous pancreas-kidney transplantation (SPK) models with portal venous drainage and systemic venous drainage to compare the impact of venous drainage site on acute rejection in pig. METHODS: Forty-eight nonrelated, first hybrid landrace pigs were divided into PE (portal-enteric drainage) and SE (systemic-enteric drainage) groups. Type I diabetes mellitus was induced by whole pancreatectomy, and right-side nephrectomy was also performed in the recipients. The donor portal vein was anastomosed to superior mesenteric vein of the recipients in PE group or to the inferior hepatic cava vena of the recipients in SE group. Graft tissue specimens were obtained with laparotomy on Day 3 and 7 after transplant, and the severity of acute rejection was scored according to Nakhleh and Banff criteria. RESULTS: The cold ischemia time, fasting plasma glucose and urine creatinine of the 2 groups had no statistic difference between 2 groups at Day 1, 3, 5, and 7 after transplant (P>0.05). The occurrence of both pancreas and kidney acute rejections in PE group was significant later and slighter than SE group (P<0.05). CONCLUSION: PVD, compared with SVD, could ameliorate and delay acute rejection in pig SPK. It might become a tolerance inducing method of pancreas transplantation, decrease the cost and improve the quality of SPK, if further confirmed by clinical trials.
Assuntos
Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Transplante de Rim/métodos , Transplante de Pâncreas/imunologia , Transplante de Pâncreas/métodos , Veias/fisiologia , Veias/cirurgia , Doença Aguda , Animais , Rejeição de Enxerto/patologia , SuínosRESUMO
OBJECTIVE: To study the early diagnosis value of acute rejection response to perforin and granzyme B protein expressions around transplantation pancreas tissue after pancreatic transplantation. METHODS: Twenty-four hybrid landraces were randomly divided into three groups [control group ( I group), transplantation group ( II group), transplantation + immunosuppressive group (III group)]. The transplantation group was treated by pancreatoduodenal allotransplantation, and simultaneously the group of transplantation + immunosuppressants was intervened by cyclosporin A (CsA), mycophenolate mofetil (MMF) and metrisone. The peripheral venous blood was sampled via subclavian vein one day before operation and on the 1st, 3rd, 5th or 7th day after operation respectively, and then the glucose, insulin and glucagons in serum were measured. The grafted pancreatic tissues were collected for pathologic and immunohistochemical examinations at 1st, 3rd, 5th and 7th day after operation. RESULTS: (1) The levels of blood sugar, insulin and glucagons had no significant difference among groups of control, transplantation and transplantation + immunosuppressant group (P>0.05). (2) By comparing with two experimented groups, the expressions of perforin and granzyme B protein in transplantation pancreas tissue had a significant difference between transplantation group and transplantation + immunosuppressive group (P < 0.05). (3) The time of perforin and granzyme B protein expressions in transplantation pancreas tissue after transplantation was 2-4 days earlier than that of pathological changes in acute rejection. CONCLUSION: The expression alterations of perforin and granzyme B protein are earlier appearance than the pathological changes of acute rejection response in transplantation pancreas tissue, and by combining with routine pathological examination, the acute rejection response can be diagnosed on early stage.
Assuntos
Regulação da Expressão Gênica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/metabolismo , Granzimas/metabolismo , Transplante de Pâncreas/imunologia , Perforina/metabolismo , Animais , Diagnóstico Precoce , Feminino , Rejeição de Enxerto/patologia , Humanos , Imuno-Histoquímica , Masculino , Pâncreas/imunologia , Pâncreas/metabolismo , Pâncreas/patologia , Coloração e Rotulagem , SuínosRESUMO
OBJECTIVE: To investigate the morphological alterations and significances of jejunal mucosa responsible to post-operative patients with severe acute pancreatitis treated with enteral nutrition (EN) or total parenteral nutrition (TPN). METHODS: 40 patients were divided randomly into EN group and TPN group. The serum levels of prealbumin (PAB) and transferrin (TRF) were detected at a given time. Jejunal mucosa specimens were acquired through a new technique and observed in detail both under general microscope and electronic microscope. RESULTS: On seventh and fourteenth post-operative day, the serum level of PAB in EN group was remarkably higher than it in TPN group (P < 0.05). No difference was seen in TRF levels of 2 groups. On 14th post-operative day, it was found by general microscope that the height of jejunal mucosa villi was significantly higher in EN group than in TPN group (P < 0.05), and meantime it was also found by electronic microscope that the height of microvilli on jejunal mucosa epithelial cells in EN group was remarkably higher than it in TPN group (P < 0.05) and was higher than microvilli itself before EN start (P < 0.05). In TPN group, some pathological alterations could be seen in jejunal mucosa epithelial cells on 14th post-operative day, such as mitochondrial edema, crista swelling, dilation of rough endoplasmic reticulum and nucleolus, and the appearance of abnormal substances in intercellular attachments. However, none of above these pathological changes could be seen in EN group. CONCLUSION: Early enteral nutrition could protect the jejunal mucosa in post-operative patients with severe acute pancreatitis and have its results better than TPN alone.
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Nutrição Enteral/métodos , Mucosa Intestinal/patologia , Jejuno/patologia , Pancreatite/patologia , Pancreatite/terapia , Adulto , Idoso , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/ultraestrutura , Masculino , Microscopia Eletrônica , Microvilosidades/metabolismo , Pessoa de Meia-Idade , Nutrição Parenteral , Período Pós-Operatório , Pré-Albumina/metabolismo , Fatores de Tempo , Transferrina/metabolismoRESUMO
OBJECTIVE: To investigate the early diagnosis value of bile K-ras mutation responsible for hepatic metastasis of pancreatic cancer. METHODS: While building the animal models with pancreatic cancer and hepatic metastasis of pancreatic cancer of rats, we collected bile from the model animals, and used the polymerase chain reaction and restriction fragment-length polymorphism (PCR-RFLP) to evaluate the point mutation at exon codon 12 of K-ras gene in bile. Then, the above result was compared with pathological slice. RESULTS: The positive rates of K-ras point mutation in bile were 84.2% (16/19) for the model with hepatic metastasis of pancreatic cancer, and 0.0% (0/16) for the model with pancreatic cancer without hepatic metastasis. For the model with hepatic metastasis of pancreatic cancer, the sensitivity, specificity, positive prediction or negative prediction value of surveying K-ras mutation in bile was 84.2%, 85.7%, 84.2% or 85.7% respectively. CONCLUSION: Both the mutability and the specificity of K-ras gene mutation at codon 12 in bile are high. Our above work can supply a new elemental filter method for the early diagnosis of hepatic metastasis of pancreatic cancer.
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Bile/metabolismo , Genes ras/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Mutação Puntual , Animais , Linhagem Celular Tumoral , Códon/genética , Éxons/genética , Feminino , Neoplasias Hepáticas/genética , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To study the immune tolerance induced by human Ad-CTLA-41g after pancreaticoduodenal transplantation of rats. METHODS: Wistar rats with diabetes were induced by caudal intravenous administration of streptozotocin (STZ) at a single dose of 60 mg/kg. Pancreaticoduodenal transplantations were performed with the SD rats as donors and the diabete Wistar rats as recipients. The SD pancreaticoduodenal grafts with human Ad-CTLA-41g infection via arterial perfusion in vitro were transplanted into Wistar rats with diabetes. The blood glucose of the rats was measured after transplantation. The graft functional survival time (GFST) was recorded. The concentration of IL-2 was measured by ELISA on day 3 and day 10 after operation. The human CTLA-41g was detected by Western blot after operation. RESULTS: The GFST of control group without gene transfer was (11+/- 1) d, while that of gene transfer group was (33 +/-4) d (P< 0. 01). The expression of serum human CTLA-41g was detected in rats of gene transfer group on the 10th day after transplantation, while no serum human CTLA-4Ig was detected in rats of control group without gene transfer. On the 3rd day after transplantation, the level of serum IL-2 was (33. 710+/-7. 803) pg/mL in rats of transfer group, and was (44. 772+/-9. 102) pg/mL in rats of control group without gene transfer. On the 10th day, the level of serum IL-2 was (47. 846+/-14. 050) pg/mL in rats of transfer group, and was (80. 806+/-18. 629) pg/mL in rats of control group without gene transfer. The levels of serum IL-2 in rats of transfer group was much lower than those of the control group without gene transfer (PAssuntos
Adenoviridae/genética
, Antígenos CD/genética
, Duodeno/imunologia
, Tolerância Imunológica/genética
, Imunoglobulinas/genética
, Transplante de Pâncreas/imunologia
, Pâncreas/imunologia
, Animais
, Glicemia/metabolismo
, Antígeno CTLA-4
, Duodeno/metabolismo
, Duodeno/transplante
, Feminino
, Regulação da Expressão Gênica/imunologia
, Humanos
, Interleucina-2/metabolismo
, Masculino
, Pâncreas/metabolismo
, Ratos
, Taxa de Sobrevida
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We reported the first case of simultaneous pancreas-kidney transplantation (SPK) in our hospital. The recipient is a 65 year old male, who suffered type 2 diabetes for 15 years and renal dysfunction for 5 years and other diabetic complications such as retinopathy, peripheral neuropathy. SPK was performed successfully for him in March, 2007, in which the donor kidney was put in left iliac fossa, while the donor pancreas grafted to set in right iliac fossa of recipient, with pancreas exocrine drainage controlled by anastomosis to the small bowel and endocrine release done to the circulatory system. Serum C-peptide, Creatinine and Blood urea nitrogen became normal levels at day 1, 4 and 11 of post-operation respectively. The concentration of blood glucose was stabilized gradually to normal level and therefore the injected insulin was stopped using to the patient at day 16 of post-operative days. OGTT test showed the function of grafted pancreas was normal 3 weeks after transplant, and no transplantation-related complications occurred. With the recipient followed up for 6 months, both his blood glucose level and renal function maintained normal without using injected insulin, and he was getting to recover from other diabetic complications also.