RNA interference suppression of mucin 5AC (MUC5AC) reduces the adhesive and invasive capacity of human pancreatic cancer cells

<p>Abstract</p> <p>Background</p> <p>MUC5AC is a secretory mucin normally expressed in the surface muconous cells of stomach and bronchial tract. It has been known that MUC5AC <it>de novo </it>expression occurred in the invasive ductal carcinoma and pancreatic intraepithelial neoplasm with no detectable expression in normal pancreas, however, its function remains uncertain. Here, we report the impact of MUC5AC on the adhesive and invasive ability of pancreatic cancer cells.</p> <p>Methods</p> <p>We used two MUC5AC expressing cell lines derived from human pancreatic cancer, SW1990 and BxPC3. Small-interfering (si) RNA directed against MUC5AC were used to assess the effects of MUC5AC on invasion and adhesion of pancreas cancer cells <it>in vitro </it>and <it>in vivo</it>. We compared parental cells (SW1990 and BxPC3) with MUC5AC suppressed cells by si RNA (si-SW1990 and si-BxPC3).</p> <p>Results</p> <p>MUC5AC was found to express in more than 80% of pancreatic ductal carcinoma specimens. Next we observed that both of si-SW1990 and si-BxPC3 showed significantly lower adhesion and invasion to extracellular matrix components compared with parental cell lines. Expression of genes associated with adhesion and invasion including several integerins, matrix metalloproteinase (MMP) -3 and vascular endothelial growth factor (VEGF) were down-regulated in both MUC5AC suppressed cells. Furthermore, production of VEGF and phosphorylation of VEGFR-1 were significantly reduced by MUC5AC down regulation. Both of si-SW1990 and si-BxPC3 attenuated activation of Erk1/2. <it>In vivo</it>, si-SW1990 did not establish subcutaneous tumor in nude mice.</p> <p>Conclusions</p> <p>Knockdown of MUC5AC reduced the ability of pancreatic cancer cells to adhesion and invasion, suggesting that MUC5AC might contribute to the invasive motility of pancreatic cancer cells by enhancing the expression of integrins, MMP-3, VEGF and activating Erk pathway.</p

Tumor-Infiltrating Lymphocytes and Macrophages as a Significant Prognostic Factor in Biliary Tract Cancer

Background: The impact of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) on the prognosis of biliary tract cancer (BTC) is not completely understood. Therefore, in our study, we investigated the effects of the various immune cells infiltration in tumor microenvironment (TME). Methods: A total of 130 patients with BTC who underwent surgical treatment at our institution were enrolled in this study. We retrospectively evaluated TILs and TAMs with immunohistochemical staining. Results: With CD8-high, CD4-high, FOXP3-high, and CD68-low in TME as one factor, we calculated Immunoscore according to the number of factors. The high Immunoscore group showed significantly superior overall survival (OS) and recurrence-free survival (RFS) than the low Immunoscore group (median OS, 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p \u3c 0.001). Also, high Immunoscore was an independent good prognostic factor for OS and RFS (hazards ratio 2.05 and 2.41 and p = 0.01 and p = 0.001, respectively). Conclusions: High Immunoscore group had significantly superior OS and RFS and was an independent good prognostic factor for OS and RFS

Two Cases of Long-Term Control of Metastatic Colorectal Cancer via FTD/TPI plus Bevacizumab in Elderly Patients

With advances in new cytotoxic drugs and molecular-targeted drugs, the prognosis of patients with metastatic colorectal cancer (mCRC) has improved. However, physicians often hesitate to administer intensive standard regimens to elderly patients with mCRC. Recently, first-line regimens that are effective in and well-tolerated by patients who are not eligible for intensive chemotherapy have been established. However, the therapeutic strategies to adopt after the failure of first-line treatment for patients who are not eligible for intensive chemotherapy remain unclear. We herein report two cases of long-term control of mCRC via FTD/TPI+bevacizumab (Bmab) as second- or third-line treatment in elderly patients without severe adverse events. In case 1, first-line treatment with Tegafur-Uracil, which is a prodrug of 5-FU, caused disease progression in a short period after the initiation of chemotherapy. In case 2, intensive first-line treatment caused severe adverse events, and treatment was discontinued. However, in both cases, disease control was obtained for a long time without severe adverse events by subsequent treatment with FTD/TPI+Bmab. The success in these present cases indicates that FTD/TPI+Bmab as a second- or third-line treatment is a therapeutic option for elderly patients with mCRC who are not eligible for intensive chemotherapy, even after failure of treatment with 5-FU

Complete Response of Pulmonary Metastases from Rectal Cancer to Tegafur-Uracil/Leucovorin plus Bevacizumab in an Elderly Patient: A Case Report

As a result of recent major advances in chemotherapy for metastatic colorectal cancer, the prognosis for patients with metastatic colorectal cancer has improved. However, elderly patients often cannot receive intensive therapy. There are still many problems to solve regarding treatment for elderly patients with metastatic colorectal cancer. We herein report a case of complete response of pulmonary metastases from rectal cancer to tegafur-uracil (UFT)/leucovorin (LV) + bevacizumab (Bmab) in an elderly patient. An 80-year-old woman who had undergone curative surgery for rectal cancer 5 years ago was diagnosed with pulmonary metastases. Taking into account her advanced age and low renal function (creatinine clearance: 41.2 mL/min), UFT/LV + Bmab therapy was selected. The patient received UFT (300 mg/m2/day) and LV (75 mg/day) on days 1–5, 8–12, and 15–19 and Bmab (7.5 mg/kg) on day 1. The treatment cycle was repeated every 21 days. Following 17 courses of treatment without adverse events, a complete response was observed. Furthermore, there was no recurrence within 6 months after the final course of therapy. This case indicates that UFT/LV + Bmab is suitable for the treatment of elderly patients with metastatic colorectal cancer

Impact of laparoscopic surgery on short‐term and long‐term outcomes in elderly obese patients with colon cancer

[Background] Laparoscopic surgery is reported to be useful in obese or elderly patients with colon cancer, who are at increased risk of postoperative complications because of comorbidities and physical decline. However, its usefulness is less clear in patients who are both elderly and obese and may be at high risk of complications. [Methods] Data for obese patients (body mass index ≥25) who underwent laparoscopic or open surgery for stage II or III colon cancer between January 2009 and December 2013 were collected by the Japan Society of Laparoscopic Colorectal Surgery. Surgical outcomes, postoperative complications, and relapse-free survival (RFS) were compared between patients who underwent open surgery and those who underwent laparoscopic surgery according to whether they were elderly (≥70 y) or nonelderly (<70 y). [Results] Data of 1549 patients (elderly, n = 598; nonelderly, n = 951) satisfied the selection criteria for analysis. Length of stay was shorter and surgical wound infection was less common in elderly obese patients who underwent laparoscopic surgery than in those underwent open surgery. There were no significant between-group differences in overall complications, anastomotic leakage, ileus/small bowel obstruction, or RFS. There were also no significant differences in RFS after laparoscopic surgery according to patient age. [Conclusion] Laparoscopic surgery is safe in elderly obese patients with colon cancer and does not worsen their prognosis. There was no significant difference in the effectiveness of laparoscopic surgery between obese patients who were elderly and those who were nonelderly

External Pancreatic Juice Drainage Through a Percutaneous Endoscopic Drainage Tube for the Patient With a Postoperative Pancreatic Juice Leakage

Percutaneous endoscopic gastrostomy (PEG) has been widely accepted for patients who have no swallowing ability but have an intact gut. Its clinical application is mainly for nutritional support and decompression of the intestine in patients with bowel obstruction. In this paper, we report external pancreatic juice drainage through a percutaneous endoscopic drainage tube in a patient with postoperative pancreatic juice leakage. Soon after this procedure, pancreatic juice leakage subsided. This procedure was minimally invasive for the patient and may be a new application of PEG to maintain the good quality of life (QOL) in a patient with pancreatic juice leakage

Phosphorylated Smad2 in Advanced Stage Gastric Carcinoma

<p>Abstract</p> <p>Background</p> <p>Transforming growth factor β (TGFβ) receptor signaling is closely associated with the invasion ability of gastric cancer cells. Although Smad signal is a critical integrator of TGFβ receptor signaling transduction systems, not much is known about the role of Smad2 expression in gastric carcinoma. The aim of the current study is to clarify the role of phosphorylated Smad2 (p-Smad2) in gastric adenocarcinomas at advanced stages.</p> <p>Methods</p> <p>Immunohistochemical staining with anti-p-Smad2 was performed on paraffin-embedded specimens from 135 patients with advanced gastric adenocarcinomas. We also evaluated the relationship between the expression levels of p-Smad2 and clinicopathologic characteristics of patients with gastric adenocarcinomas.</p> <p>Results</p> <p>The p-Smad2 expression level was high in 63 (47%) of 135 gastric carcinomas. The p-Smad2 expression level was significantly higher in diffuse type carcinoma (p = 0.007), tumours with peritoneal metastasis (p = 0.017), and tumours with lymph node metastasis (p = 0.047). The prognosis for p-Smad2-high patients was significantly (p = 0.035, log-rank) poorer than that of p-Smad2-low patients, while a multivariate analysis revealed that p-Smad2 expression was not an independence prognostic factor.</p> <p>Conclusion</p> <p>The expression of p-Smad2 is associated with malignant phenotype and poor prognosis in patients with advanced gastric carcinoma.</p

A case of perforation of a pancreatic duct by a pancreatic stent during chemoradiotherapy for pancreatic head cancer: a case report

Abstract Background Pancreatic injuries are rare, and no treatment plan has yet been established for grade III injuries. In many cases, pancreatic stent placement has resulted in saving patients. However, some cases of perforation of a pancreatic duct during the placement of a stent have been described, and there are also a few cases of delayed perforation by a pancreatic stent. Case presentation A 62-year-old man had obstructive jaundice and pancreatitis due to locally advanced pancreatic head cancer. Both biliary and pancreatic stent were placed by endoscopy, after which chemoradiotherapy was performed. Four months later, he visited our hospital with severe abdominal pain. We performed enhanced CT and diagnosed the patient as having a perforation of a pancreatic duct by a pancreatic stent; therefore, we performed an emergency operation. Since we deemed pancreatectomy risky, we inserted pancreatic tubes into both sides of the perforated site and performed percutaneous transgastric drainage. The postoperative course was uneventful. We thereafter cut the tubes and switched to internal drainage. Conclusion Many cases of pancreatic injuries have reported that pancreatic stent placement results in saving the patient, but there have been few cases in which a pancreatic stent causes perforation of a pancreatic duct. External drainage by pancreatic tubes is very effective in resolving perforation of a pancreatic duct