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Comprehensive Treatment for Carcinoma of Body and Tail of Pancreas

Progress and Puzzle on Therapy of Carcinoma of Body and Tail of Pancreas 

胰腺癌組織中 Beclin-1 mRNA 和 miR-216a 的表達及 VEGF 蛋白表達與 p-MAPK-ERK1/2信號通路的關系

目的 探討腺癌、鱗癌、黏液性囊腺瘤、慢性胰腺炎和正常胰腺組織中胰腺癌相關基因的表達。 方法 回顧性收集 2012 年 1 月至 2017 年 4 月期間于湖北醫藥學院附屬東風醫院肝膽胰外科住院行手術治療的 40 例胰腺疾病患者的術中標本，其中腺癌、鱗癌、黏液性囊腺瘤、慢性胰腺炎和正常胰腺組織各 8 例。采用實時熒光定量 PCR 和基因芯片法檢測 5 組組織中 Beclin-1 mRNA 和 microRNA（miR）-216a 的表達。對以上組織行原代細胞培養，分為空白對照組和 PD98095 組（加入 PD98095 抑制劑），采用 Western blot 法檢測細胞中血管內皮生長因子（VEGR）與磷酸化細胞外調節蛋白激酶 1/2（p-ERK1/2）的表達。 結果 與正常對照組比較，腺癌組和鱗癌組組織中 Beclin-1 mRNA 和 miR-216a 的表達水平較低（P<0.05），腺癌組、鱗癌組、黏液性囊腺瘤組和慢性胰腺炎組組織中 Beclin-1 mRNA 和 miR-216a 的表達水平比較差異無統計學意義（P>0.05）。與同類組織的空白對照組比較，腺癌組和鱗癌組加入 PD98095 后，細胞中 p-ERK1/2 和 VEGF 蛋白的表達水平下調（P<0.05），但黏液性囊腺瘤組、慢性胰腺炎組和正常對照組加入 PD98095 前后細胞中 p-ERK1/2 及 VEGF 蛋白的表達水平變化不大（P>0.05）。 結論 Beclin-1 mRNA、miR-216a 和 VEGF 蛋白的表達與胰腺癌的發生發展可能有關。

Apoptotic Effect on Pancreatic Adenocarcinoma Cell BxPC-3 in Subcutaneous Transplantation Tumor of Nude Mice Induced by Sulfasalazine and 5-Fluouracil

Objective　To explore the effect on apoptotic genes of pancreatic adenocarcinoma cell BxPC-3 from subcutaneous transplantation tumor in nude mice induced by 5-FU and sulfasalazine (SZ).Methods　Changes of apoptosis-related genes 〔bcl-2, cyclinD1, Bax and NF-κB (p65)〕 in subcutaneous transplantation tumor treated by 5-FU, SZ alone or both at the levels of mRNA and protein were measured by RT-PCR and Western blot. Results　NF-κB (p65) at mRNA relative content and protein expression in subcutaneously heterotopic transplantation tumor treated by 5-FU (7.5, 15 mg/kg), SZ (10, 20 mg/kg) alone or both showed significant difference, except for two subsets in SZ group, respectively, in comparison with each control group (P＜0.01). Meanwhile bcl-2 and cyclinD1 at the levels of mRNA and protein, and Bax protein level were significantly different from each control group (P＜0.01). The above-mentioned indexes were show obvious interaction of both by multiple factor analysis of variance. Conclusion　Up-regulated level of Bax, down-regulated levels of bcl-2, cyclinD1 and NF-κB (p65) might be one of apoptotic mechanisms that SZ synergistically enhanced apoptotic effect on pancreatic adenocarcinoma cell BxPC-3 of subcutaneous transplantation tumor in nude mice induced by 5-FU.

Effect of Recombinant Tissue Factor Pathway Inhibitor 2 Gene on The Invasion of Human Pancreatic Cancer in Vitro and in Vivo

Objective 　To investigate the invasion ability of Panc-1 cells in vivo and in vitro af ter being t ransfected with tissue factor pathway inhibitor 2 gene ( TFPI-2) . Methods 　The expression vector pEGFP-C1-TFPI-2 was transfected into human pancreatic cancer line Panc-1 cells by using liposome. TFPI-2 mRNA and protein of transfected and nontransfected cells were detected by reverse t ranscription-polymerase chain reaction (RT-PCR) and Western blot respectively. The tumor cells invasive behavior of t ransfected ( Panc-1-TFPI-2) and nontransfected ( Panc-1-V and Panc-1-P) cells were assessed in vitro through Boyden Chamber method. The transfected and nontransfected cells were implanted into nude mice to observe it s growth and metastasis in vivo. Results 　Expressions of mRNA and protein of TFPI-2 were confirmed in transfected cells. Af ter TFPI-2 t ransfection , the number of Panc-1-TFPI-2 , Panc-1-V and Panc-1-P cells passing through membrane of Boyden Chamber were 24. 4 ±3. 5 ,61. 3 ±4. 1 and 60. 2 ±3. 9 , respectively. The number of TFPI-2-expressing cells to t raverse a Matrigel-coated membrane was obviously decreased compared with that of non-expressing cells , the invasion ability was lower than that before transfection in vitro. The subcutaneous tumor volume of the Panc-1-TFPI-2 group was (438. 0 ±69. 8) mm3 , the Panc-1-V group was (852. 0 ±102. 9) mm3 and the Panc-1-P group was (831. 0 ±78. 1) mm3 , P lt; 0. 05. The metastasis to liver and lung and muscular invasion occurred in the Panc-1-V group and the Panc-1-P group. There were no muscular invasion and metastatic lesions in the Panc-1-TFPI-2 group. Conclusion 　TFPI-2 gene expression may obviously inhibit the invasion ability of pancreatic cancer cells in vitro and in vivo , which provides an experimental basis for the treatment of human pancreatic cancer by gene therapy.

Values of CA199, CA242, CEA, and CA125 in Diagnosis and Prognosis for Pancreatic Cancer

ObjectiveTo explore the values of CA19-9, CA242, CEA, and CA125 single or combined detection on clinical diagnosis and prognosis for patients with pancreatic cancer. MethodsSerum tumor markers CA199, CA242, CEA, and CA125 of 63 patients with pancreatic cancer, 33 patients with cancer of bile duct, and 27 patients with benign pancreatic disease were detected, and those patients were followed up after operation. ResultsThe levels of CA19-9, CA242, CEA, and CA125 in patients with pancreatic cancer were significantly higher than those in patients with benign pancreatic disease and cancer of bile duct (Plt;0.05). The sensitivity of CA19-9 alone was the highest in the four tumor markers for the patients with pancreatic cancer 〔79.4% (50/63)〕, but the specificity (61.9%) was lower than that of CA242 (83.3%) and CEA (80.0%). The specificity of combined detection of CA199+CA242+CEA was the highest 〔93.3% (56/60)〕. The level of CA19-9 in carcinoma of body/tail of pancreas was significantly higher than that of carcinoma of pancreas head or whole pancreas (Plt;0.05). The serum levels of CA19-9 and CA242 in patients with stage Ⅳ were significantly higher than those in stage Ⅰ or Ⅱ/Ⅲ (Plt;0.05). Fifteen patients were lost to follow up, 48 patients were followed up 2－12 months with an average 6 months. The levels of CA242 and CA199 in patients with pancreatic cancer on 0.5 month and 3 months after operation were lower than those before operation (Plt;0.05). ConclusionsSingle detection of CA19-9 can improve the diagnostic sensitivity, and combined detection of tumor markers CA199+CA242+CEA can improve the diagnostic specificity. CA19-9 or CA242 is a valuable marker for evaluating treatment effects and estimating prognosis.

Clinical status of advanced pancreatic cancer treated with high intensity focused ultrasound

ObjectiveTo explore the application value of high intensity focused ultrasound (HIFU) in the treatment of advanced pancreatic cancer.MethodThe domestic and foreign literatures about studies of HIFU treating advanced pancreatic cancer in recent years were retrieved and summarized.ResultsHIFU could prolong the survival time, control pain, and enhance the body’s immune function in patients with advanced pancreatic cancer. There were no obvious serious complications during the treatment process. The combined treatment with radiotherapy, chemotherapy, and traditional Chinese medicine could obviously prolong the survival time and improve the quality of life for the patients with advanced pancreatic cancer.ConclusionsHIFU is an important component in the comprehensive treatment of advanced pancreatic cancer. However, because there is no uniform standard for the dosage of HIFU treatment, the sample size of many related studies is small, so the research results have certain limitations, so more studies are needed to improve their understanding of advanced pancreatic cancer in order to better serve clinical workin future.

Cancer associated fibroblasts promote growth of primarily cultured pancreatic ductal adenocarcinoma cells in vitro and tumor formation in patient-derived tumor xenograft model

ObjectiveTo optimize the culture method of human primary pancreatic ductal adenocarcinoma (PDAC) cells and cancer associated fibroblasts (CAFs) and investigate the effect of CAFs on the growth of primary PDAC cells in vitro and tumor formation in patient-derived xenograft (PDX) model.MethodsThe PDAC specimens were collected and primarily cultured. In order to observe the effect of CAFs on the growth of primary PDAC cells in vitro, the CAFs were co-cultured with primary PDAC cells consistently and the alone cultured primary PDAC cells served as the control. Then, these cells were injected into the shoulder blades of NOG mice in order to develop the PDX model.ResultsWhen the primary PDAC cells separated from the CAFs, the proliferation capacity of the primary PDAC decreased rapidly in the passage culture in vitro, and the most cells were terminated within 5 generations. By contrast, when the CAFs co-cultured with the primary PDAC cells, the proliferation capacity of primary PDAC cells were preserved, which could be stably transferred to at least 10 generations. The tumors of NOG mice were detected during 2–3 weeks after injecting the mixed cells (primary PDAC plus CAFs), while had no tumor formation after injecting CAFs alone. The rate of tumor was 92.9% (13 cases) in the primary PDAC plus CAFs group, which was higher than that of the CAFs alone group (64.3%, 9 cases), but there was no statistical difference because of the small sample size. The volume of tumor in the primary PDAC plus CAFs group at 2, 4, 6, and 8 weeks after the tumor cells injection was significantly larger than that in the CAFs alone group at the corresponding time point, the differences were statistically significant (P<0.01).ConclusionsThe CAFs could promote the growth of primary PDAC cells in vitro. This new method of co-culture CAFs with primary PDAC could improve the success rate of primary PDAC cells culture and improve the success rate of PDX model in NOG mice.

Treatment strategies for different types of pancreatic cancer

ObjectiveTo explore the treatment strategies of different types of pancreatic cancer.MethodsBy reading the relevant literatures on the treatment of pancreatic cancer at home and abroad in recent years, the classification of pancreatic cancer and the progress of treatment measures were summarized.ResultsAccording to preoperative imaging evaluation, pancreatic cancer was divided into resectable pancreatic cancer, borderline resectable pancreatic cancer, locally advanced pancreatic cancer, and pancreatic cancer with distant metastasis. Resection of pancreatic cancer should be radical resection, supplemented with chemotherapy after surgery; patients with resected pancreatic cancer in the junction, if the patient with venous invasion could be resected and reconstructed, it was recommended to undergo surgery and postoperative adjuvant chemotherapy. Patients with unresectable reconstruction and arterial invasion should undergo neoadjuvant therapy, and then re-evaluate the resectability of the tumor to determine whether surgery was feasible. Patients with locally advanced or combined metastatic pancreatic cancer had lost the opportunity for surgery, for this kind of patient, advocated neoadjuvant chemoradiotherapy or second-line combined targeted therapy.ConclusionsMost patients with pancreatic cancer have progressed to the stage of clinical diagnosis. They are familiar with the treatment of different types of pancreatic cancer and take targeted treatment measures to improve the survival time of patients.

Pancreatic Carcinoma: Diagnosis and Preoperative Resectability Assessment by Using Gd-DTPA 3D FSPGR Dynamic MR Imaging

ObjectiveTo study the value of Gd-DTPA three dimension fast spoiled gradientecho (3D FSPGR) dynamic MRI in the diagnosis and preoperative respectability assessment of pancreatic carcinoma.MethodsThirty-two cases of pancreatic carcinoma verified by surgery and pathology were included in this study. All of the cases had MRI examinations two weeks before surgery. MRI protocols involved gradient echo T1 weighted（GRE T1W） with fat suppression, fast spin echo respiratory gating T2 weighted (FSE RG T2W) with fat suppression, MR cholangiopancreatography (MRCP) and gadolinium chelate 3D FSPGR T1W dynamic enhancement. Two radiologists reviewed MRI of the 32 cases retrospectively. Preoperative resectability of pancreatic carcinoma was assessed according to the characteristics of tumor lesions, peripancreatic invasion, vascular invasion, lymph node metastases, and liver metastases. The diagnosis and preoperative resectability assessment of pancreatic carcinoma by MRI was compared with surgical findings. ResultsOf 32 cases, 29 cases diagnosed by MRI were confirmed by surgery and pathology (accuracy of MRI, 90.6%). The sensitivity was 84.4%(27/32) and 93.8%(30/32) respectively for GRE T1W with fat-suppression combining FSE RG T2W and for Gd-DTPA 3D FSPGR dynamic MRI in the detection of pancreatic tumors. The accuracy was 87.5%（21/24）, 87.0%（20/23）, 80.0%（12/15）, 88.9%（8/9） and 83.3%（5/6） respectively for Gd-DTPA 3D FSPGR dynamic MRI in assessing local extension, vascular invasion, lymph node metastases, liver metastases and peritoneal carcinomatosis of pancreatic carcinoma. Eight cases of pancreatic carcinoma were considered to be resectable by enhanced MRI, while the tumors in 7 cases of the 8 cases were resected by surgery. Twentythree cases were confirmed nonresectable by surgery in the 24 cases of pancreatic carcinoma considered to be non-resectable by enhanced MRI. The sensitivity, specificity and accuracy were 87.5%，95.8% and 93.8% resectability for the assessment of respectability of pancreatic carcinoma by using Gd-DTPA 3D FSPGR dynamic MRI. There was no significant difference in the assessment of the resectability of pancreatic carcinoma between enhanced MRI and surgery or pathology （κ=0.83）.ConclusionUsing of Gd-DTPA 3D FSPGR dynamic enhanced MRI improves the detections of pancreatic carcinoma and metastasis. It is also accurate in the assessment of the resectability of pancreatic carcinoma.