Survival Benefits of Laparoscopic Gastrectomy in Elderly Patients With Gastric Cancer: Focusing on Preoperative Nutritional and Inflammatory Status.

BACKGROUND/AIM: Laparoscopic gastrectomy (LG) may have greater clinical benefits as a less invasive surgery for elderly patients with gastric cancer (GC). Therefore, we aimed to evaluate the survival benefit of LG in elderly patients with GC, especially focusing on preoperative comorbidities, and nutritional and inflammatory status. PATIENTS AND METHODS: Data collected from 115 patients aged ≥75 years with primary GC who underwent curative gastrectomy, comprising 58 patients who underwent open gastrectomy (OG) and 57 patients who underwent LG, were retrospectively reviewed (total cohort), and 72 propensity-matched patients (matched cohort) were selected for survival analysis. The aim of the study was to determine short- and long-term outcomes, and the clinical markers to identify a population who may benefit from LG in elderly patients. RESULTS: The complication and mortality rates as a short-term outcome in the total cohort and overall survival (OS) as a long-term outcome in the matched cohort did not differ significantly between the groups. In the total cohort, advanced tumor stage and ≥3 comorbidities were independent factors for poor prognosis in terms of OS [hazard ratio (HR)=3.73, 95% confidence interval (CI)=1.78-7.78, p<0.001 and HR=2.50, 95% CI=1.35-4.61, p<0.01, respectively]. The surgical approach was not an independent risk factor for postoperative complications (grade ≥III) and OS. In subgroup analysis of the total cohort, patients with a neutrophil-lymphocyte ratio (NLR) ≥3 in the LG group demonstrated a trend toward greater OS (HR=0.26, 95% CI=0.10-0.64, interaction p<0.05). CONCLUSION: LG might offer greater survival benefits than OG in frail patients such as those with high NLR.

Survival benefits of gastrectomy compared to conservative observation for older patients with resectable gastric cancer: a propensity score matched analysis.

PURPOSE: Radical gastrectomy is considered the first choice of curative treatment for older patients with gastric cancer (GC). However, there is limited data on the survival benefits of gastrectomy for older patients with GC. METHODS: This was a retrospective observational study where medical records of patients aged ≥ 75 years with clinically resectable primary GC, comprising 115 patients who underwent radical surgery (S group) and 33 patients who received conservative therapy (non-S group) (total cohort) and 44 propensity-matched patients (matched cohort), were reviewed. Survival and independent risk factors, including comorbidities and systemic nutritional and inflammatory statuses, were evaluated. RESULTS: In the total cohort, the 5-year overall survival (OS) in the S group was significantly higher than that in the non-S group (53.7% vs 19.7%, P < 0.0001). In the matched cohort, the 3-year OS in the S group was significantly higher than that in the non-S group (59.4% vs 15.9%, P < 0.01). Multivariate analysis of the total cohort showed that no surgery was an independent prognostic factor for poor OS (hazard ratio (HR) 3.70, 95% confidence interval (CI) 1.91-7.20, P = 0.0001). In the S group in the total cohort, the multivariate analysis showed that renal disease (HR 2.51, 95% CI 1.23-5.12, P < 0.05) was an independent prognostic factor for poor OS. CONCLUSIONS: Gastrectomy for older patients improved the prognosis; however, careful patient selection is essential, especially among those with renal disease.

Successful outcome of retrograde pancreatojejunostomy for chronic pancreatitis and infected pancreatic cysts: A case report.

BACKGROUND: Chronic pancreatitis occasionally requires surgical treatment that can be performed with various techniques. Often, this type of surgery presents with postoperative complications. We report a case of a successful retrograde pancreatojejunostomy for chronic pancreatitis and infected pancreatic cysts. CASE SUMMARY: A 62-year-old male with a 10-year history of chronic pancreatitis presented with epigastric pain for one week and a 20 kg weight loss over one year. Computed tomography showed stones in the pancreas (mainly the head), expansion of the main pancreatic duct, and thinning of the pancreatic parenchyma. Magnetic resonance imaging showed infected pancreatic cysts connected to the stomach with a fistula from the splenic hilum to the caudal portion of the liver's lateral segment. An endoscopic retrograde pancreatography was performed; the guide wires could not pass through the stones in the pancreas and therefore, drainage of the main pancreatic duct was not achieved. Next, a distal pancreatomy and splenectomy were performed; however, the pancreatic juice in the remaining parenchyma was blocked by the stones. Hence, we performed a retrograde pancreatojejunostomy and Roux-en-Y anastomosis. The patient had no postoperative complications and was discharged from the hospital on postoperative day 14. CONCLUSION: A distal pancreatomy, retrograde pancreatojejunostomy, and Roux-en-Y anastomosis could be an effective surgical procedure for intractable chronic pancreatitis.

Schwannoma mimicking pancreatic carcinoma: A case report.

BACKGROUND: Schwannoma of the pancreas is extremely rare. We report a case of pancreatic schwannoma that was difficult to distinguish from pancreatic carcinoma before surgery. CASE SUMMARY: A 66-year-old male underwent a right-lobe hepatectomy for hepatocellular carcinoma. Post-surgical computed tomography showed a 10 mm long solid mass with ischemia, with no expansion into the main pancreatic duct. Upon magnetic resonance cholangiopancreatography, the tumor had high signal intensity in diffusion weighted images, consistent with pancreatic carcinoma. Endoscopic ultrasound (EUS) was performed to obtain more information about the tumor, and showed a 14 mm solid and hypoechoic mass in the pancreatic body. Contrast enhanced EUS revealed that the tumor showed a hyperechoic mass in the early phase, and the contrasting effect continuation was very short; findings also consistent with pancreatic carcinoma. Thus, we preoperatively diagnosed his condition as a pancreatic carcinoma and performed distal pancreatectomy with splenectomy. Microscopic examination showed that the tumor was in fact a benign schwannoma. Histology showed a proliferation of spindle-shaped cell in a vague fascicular and haphazard pattern, with palisading arrangement. CONCLUSION: Schwannoma of the pancreas is very rare, however, clinicians should consider schwannoma as the differential diagnosis for pancreatic tumors.

The influence of the interval between percutaneous transhepatic gallbladder drainage and cholecystectomy on perioperative outcomes: a retrospective study.

BACKGROUND: Percutaneous transhepatic gallbladder drainage (PTGBD) is recommended for acute cholecystitis patients at high risk for surgical treatment. However, there is no evidence about the best timing of surgery after PTGBD. Here, we retrospectively investigated the influence of the interval between PTGBD and surgery on perioperative outcomes and examined the optimal timing of surgery after PTGBD. METHODS: We performed a retrospective analysis of 22 patients who underwent cholecystectomy after PTGBD from January 2008 to August 2019. We examined perioperative factors between patients with an interval of ≤ 7 days between PTGBD and cholecystectomy (≤ 7-day group; n = 12) and those with an interval of ≥ 8 days (≥ 8-day group; n = 10). Moreover, we also examined perioperative factors between patients with an interval of ≤ 14 days from PTGBD to cholecystectomy (≤ 14-day group; n = 10) and those with an interval of ≥ 15 days (≥ 15-day group; n = 12). RESULTS: Of the 22 patients, 9 had Grade I cholecystitis, 12 had Grade II cholecystitis, and 2 had Grade III cholecystitis. Nine patients had high-grade cholecystitis before PTGBD and 13 had a poor general condition. We examined perioperative factors between patients with an interval of ≤ 7 days between PTGBD and cholecystectomy (≤ 7-day group; n = 12) and those with an interval of ≥ 8 days (≥ 8-day group; n = 10). The C-reactive protein (CRP) level before surgery was significantly higher (12.70 ± 1.95 mg/dL vs. 1.13 ± 2.13 mg/dL, p = 0.0007) and the total hospitalization was shorter (17.6 ± 8.0 days vs. 54.1 ± 8.8 days, p = 0.0060) in the ≤ 7-day group than in the ≥ 8-day group. We also examined perioperative factors between patients with an interval of ≤ 14 days from PTGBD to cholecystectomy (≤ 14-day group; n = 14) and those with an interval of ≥ 15 days (≥ 15-day group; n = 8). The CRP level before surgery was significantly higher (11.13 ± 2.00 mg/dL vs. 0.99 ± 2.64 mg/dL, p = 0.0062) and the total hospitalization was shorter (19.5 ± 7.2 days vs. 59.9 ± 9.5 days, p = 0.0029) in the ≤ 14-day group than in the ≥ 15-day group. However, there were no significant differences between the ≤ 14-day group and the ≥ 15-day group in the levels of hepatic enzymes before surgery, adhesion grade, amount of bleeding during surgery, operative duration, frequency of surgical complications, or length of hospitalization after surgery. CONCLUSIONS: The interval between PTGBD and surgery has little influence on perioperative outcomes.

Intra-abdominal Desmoid-Type Fibromatosis Mimicking Diverticulitis With Abscess: A Case Report.

BACKGROUND: Intra-abdominal desmoid-type fibromatosis (DF) rarely necessitates emergency surgery. However, the condition is difficult to diagnose preoperatively and can become life-threatening if left untreated. CASE REPORT: A 46-year-old man complained of fever and right lower quadrant pain. In computed tomography, the mesenteric side of the ascending colon demonstrated air and fluid collections, suggesting diverticulitis with abscess. After 2 weeks of conservative treatment with fasting, the patient started to consume food; nonetheless, fever returned. Colonoscopy and contrast enema detected a fistula extending from the ascending colon to the abscess, with no surrounding lesions. Surgery was then performed because the abscess was refractory. During laparotomy, the scar tissue of the abscess was found to be attached to the lateral wall of the ascending colon. Hence, right colectomy combined with abscess resection was performed. Histopathological findings revealed DF in the mesentery. CONCLUSION: Although rare, DF should be included in the preoperative differential diagnosis of intra-abdominal abscesses.

PI3K inhibitor LY294002, as opposed to wortmannin, enhances AKT phosphorylation in gemcitabine-resistant pancreatic cancer cells.

LY294002 and wortmannin are chemical compounds that act as potent inhibitors of phosphoinositide 3-kinases (PI3Ks). Both of them are generally used to inhibit cell proliferation as cancer treatment by inhibiting the PI3K/protein kinase B (AKT) signaling pathway. In this study, LY294002 (but not wortmannin) showed an abnormal ability to enhance AKT phosphorylation (at Ser472) specifically in gemcitabine (GEM)-resistant pancreatic cancer (PC) cell lines PK59 and KLM1-R. LY294002 was shown to activate AKT and accumulate phospho-AKT at the intracellular membrane in PK59, which was abolished by treatment with AKTi-1/2 or wortmannin. Inhibiting AKT phosphorylation by treatment with AKTi-1/2 or wortmannin further enhanced LY294002-induced cell death in PK59 and KLM1-R cells. In addition, treatment with wortmannin alone failed to inhibit cell proliferation in both PK59 and KLM1-R cells. Thus, our results reveal that LY294002 displays the opposite effect on PI3K-dependent AKT phosphorylation, which maintains cell survival from the cytotoxicity introduced by LY294002 itself in GEM-resistant pancreatic cancer cells. We suggest that targeting the PI3K/AKT signaling pathway with inhibitors may be counterproductive for patients with PC who have acquired GEM-resistance.

[Dedifferentiated Chondrosarcoma of the Chest Wall].

A 79-year-old man complaining of an anterior chest mass with pain had an abnormal shadow on chest X-ray. A mass, 7 cm in size, with destruction of the right 4th rib was found on chest computed tomography. A F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) corresponding to the lesion showed an abnormal accumulation of FDG with the standardized uptake value(SUV) max=16.19. A malignant tumor of the chest wall origin was suspected and the tumor was resected with the 3th, 4th, and 5th ribs. Histologically, the tumor was diagnosed as dedifferentiated chondrosarcoma. He died of local recurrence about 5 months after the operation.

Hepatic resection of hepatocellular carcinoma after proton beam therapy: A case report.

Despite the widespread use of proton beam therapy (PBT) as locoregional therapy, there is currently a lack of histological evidence about the therapeutic effect of PBT for hepatocellular carcinoma (HCC). We present a case of hepatectomy and histological examination of HCC initially treated by PBT. A 76-year-old man with chronic hepatitis C underwent routine ultrasound surveillance, which revealed a 22-mm HCC in segment 4 of the liver. His hepatic reserve was adequate for surgical resection of the tumor; however, he chose to undergo PBT because of his cardiac disease. The patient received 66 Gy in 10 fractions with no toxicity exceeding grade 1. Six months after completion of PBT, contrast computed tomography showed that the tumor had increased in size to 27 mm, and the marginal part of the tumor, but not the central region, was enhanced. Additionally, two new hypervascular nodules were present in segments 5 and 6. The patient underwent surgical treatment 7 months after PBT. The operation and postoperative clinical course were uneventful. Nine months later, however, computed tomography demonstrated new, small, enhanced nodules in the remnant liver (segments 3, 5 and 6) and sacrum. In conclusion, PBT is a valuable treatment for HCC; however, it is difficult to evaluate therapeutic effect of HCC during the early post-irradiation period and provide an alternative treatment if PBT is not effective, especially in HCC cases with good liver function.

The short term feasibility of abdominoperineal resection with prostatectomy for locally advanced rectal cancer: open and laparoscopic cases report.

Total pelvic exenteration is often selected for advanced rectal cancer with prostatic invasion. The aim of this study was to evaluate the short term feasibility of the abdominoperineal resection with prostatectomy for locally advanced rectal cancer. We performed abdominoperineal resection with prostatectomy for 3 patients with locally advanced rectal cancer, including 2 patients by totally laparoscopic procedure. Patients' background, intra- and postoperative factors and short-term prognosis were evaluated. All patients underwent complete resection of primary tumor with negative surgical margins. We could perform the surgery by both open and laparoscopic procedure in collaboration with urologist. There was no operation related mortality. One patient who was treated by open procedure had urinary anastomotic leakage. No patient had recurrenced, but one patient died of other disease. Our experience suggests that open or laparoscopic abdominoperineal resection with prostatectomy could be an alternative to total pelvic exenteration for the patients with rectal cancer invading the prostate. The collaboration with the urologist would be important to perform quality-controlled surgery.

Carcinoma of the ampulla of Vater diagnosed after surgical treatment for Lemmel's syndrome.

Lemmel's syndrome encompasses a range of conditions in which a juxtapapillary duodenal diverticulum exerts mechanical and functional effects on the common bile and pancreatic ducts, leading to jaundice and pancreatitis. In this report, we describe a very rare case of carcinoma of the ampulla of Vater that was detected during postoperative follow-up in a patient who had undergone choledochojejunostomy following a diagnosis of Lemmel's syndrome. We present our clinical and pathological experiences with the diagnosis and treatment of this case as well as a review of the present literature concerning Lemmel's syndrome.

Laparoscopic and Open Resection of Gastrointestinal Stromal Tumors of the Stomach.

INTRODUCTION: Laparoscopic resection has been reported as reasonable for patients with gastrointestinal stromal tumors (GISTs). In this study, we report the feasibility of the laparoscopic approach for GIST of the stomach. We also discuss the laparoscopic approach for GIST larger than 5 cm, which is reported to be difficult to treat by laparoscopic surgery. MATERIALS AND METHODS: We retrospectively reviewed 22 patients with GIST of the stomach resected by laparoscopic or open procedures between January 2006 and February 2014. RESULTS: Laparoscopic resections were performed in 9 patients and open resections in 13 patients. Curative resections with negative resection margins were successfully completed for all patients. Although the size of the tumors was greater in open surgery cases than in laparoscopic patients (P = 0.03), the loss of blood was lower and the hospital stay was shorter in laparoscopic cases (P = 0.01 and 0.003, respectively). Laparoscopic resection was performed for 2 patients with GISTs larger than 5 cm. Both were located at greater curvature, and curatively resected without any complications or recurrence. DISCUSSION: Our experience suggests that laparoscopic surgery for GISTs of the stomach, including those larger than 5 cm, may be feasible after careful deliberation of its indications. Laparoscopic resection for GIST was associated with lower loss of blood and shorter hospital stay in comparison with open resection.

Resistance to gemcitabine in the pancreatic cancer cell line KLM1-R reversed by metformin action.

BACKGROUND/AIM: The pancreatic cancer cell line KLM1 can gain chemoresistance following gemcitabine (GEM) treatment. Metformin was found to be a useful sensitising agent towards GEM treatment following gain of chemoresistance. MATERIALS AND METHODS: The proliferation of GEM-sensitive and -resistant cells was investigated over a range of metformin concentrations from 0.005 to 5 mM. The intra- and extra-cellular energetic profiles of these two cell types under metformin exposure were investigated through adenosine triphosphate (ATP) and L-lactate assays. RESULTS: There was an unexpected decrease in intracellular L-lactate following gain of chemoresistance, despite observable medium acidification. At the biochemical level, a marked effect on phosphorylated proteins upstream of Akt, along the mTOR pathway, was observed at 6 h. These changes followed a time-dependent pattern linked closely to the changes in the energetic profile. CONCLUSION: Together, these results indicate that metformin indirectly blocks protein phosphorylation, including that of heat shock protein 27 (HSP27).

Comparative proteomic analysis of two stress-management strategies in pancreatic cancer.

BACKGROUND: It is known that cancers adopt different strategies to cope with stress and overcome adverse micro-environmental conditions. Such strategies are also applicable to chemo-therapeutic treatment, which could subsequently result in chemo-resistance. MATERIALS AND METHODS: In order to investigate known stress-evasion strategies observed in pancreatic cancer, the stress-resistant KLM1-derived cell lines KLM1-R (Gemcitabine (GEM)-induced stress) and KLM1-S (growth factor restriction-induced stress) were employed. Comparative proteomics were employed between for the two cell lines that were also compared against the parent cell line KLM1. RESULTS: Proteomic analysis revealed changes in the expression levels of 6 proteins, namely: transitional endoplasmic reticulum ATPase, lamin A/C, PDZ and LIM protein 1, calmodulin, heat shock protein 60 and alpha enolase. Resistance to GEM of KLM1-R and KLM1-S was found to be comparable, with KLM1-S cells exhibiting close to 1.5-fold higher half-maximal inhibitory concentration (IC50) compared to KLM1-R cells. CONCLUSION: These results suggest that KLM1-R can be used as a model of directly-acquired chemoresistance (responding directly to evade GEM treatment), while KLM1-S is a good model of indirectly-acquired chemoresistance (formed in response to having to survive with less availability of growth factors), additionally gaining a selective advantage upon GEM treatment.

Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration.

Slingshot-1L (SSH1L), a cofilin-phosphatase, plays a role in actin dynamics and cell migration by reactivating cofilin-1. However, the expression of SSH1L in malignant diseases is poorly understood. The overexpression of SSH1L in cancerous tissue compared to the matched surrounding non-cancerous tissues from patients with late stages (III-IV) of PC was detected in 90% (9/10) of cases by western blotting. The expression of SSH1L was shown to be upregulated in tumor cells from 10.7% (11/102) of patients with pancreatic cancer (PC) by immunohistochemistry (IHC). The positive rate of SSH1L in patients with PC at stage VI (TNM) categorized as grade 3 was of 50% (2/4) and 15% (6/40), respectively. Moreover, SSH1L expression was shown to be up-regulated in the PC cell lines (KLM1, PANC-1 and MIAPaCa-2) with high metastatic potential. Loss of SSH1L expression was associated with an increase in the phosphorylation of cofilin-1 at serine-3 and further inhibited cell migration (but not proliferation) in KLM1, PANC-1 and MIAPaCa-2. Actin polymerization inhibitor cytochalasin-D was sufficient to abrogate cell migration of PC without changing SSH1L expression. These results reveal that SSH1L is upregulated in a subset of PCs and that the SSH1L/cofilin-1 signal pathway is associated positively in PC with cell migration. Our study may thus provide potential targets to prevent and/or treat PC invasion and metastasis in patients with SSH1L-positive PC.

Gemcitabine induces poly (ADP-ribose) polymerase-1 (PARP-1) degradation through autophagy in pancreatic cancer.

Poly (ADP-ribose) polymerase-1 (PARP-1) and autophagy play increasingly important roles in DNA damage repair and cell death. Gemcitabine (GEM) remains the first-line chemotherapeutic drug for pancreatic cancer (PC). However, little is known about the relationship between PARP-1 expression and autophagy in response to GEM. Here we demonstrate that GEM induces DNA-damage response and degradation of mono-ADP ribosylated PARP-1 through the autophagy pathway in PC cells, which is rescued by inhibiting autophagy. Hypoxia and serum starvation inhibit autophagic activity due to abrogated GEM-induced mono-ADP-ribosylated PARP-1 degradation. Activation of extracellular regulated protein kinases (ERK) induced by serum starvation shows differences in intracellular localization as well as modulation of autophagy and PARP-1 degradation in GEM-sensitive KLM1 and -resistant KLM1-R cells. Our study has revealed a novel role of autophagy in PARP-1 degradation in response to GEM, and the different impacts of MEK/ERK signaling pathway on autophagy between GEM-sensitive and -resistant PC cells.

Active hexose-correlated compound down-regulates sex-determining region Y-box 2 of pancreatic cancer cells.

BACKGROUND/AIM: Active hexose-correlated compound (AHCC) is an extract of basidiomycete mushroom. It has been used as health food due to its efficacy of enhancing antitumor effects and reducing adverse effects of chemotherapy. Our previous research showed that AHCC down-regulated heat-shock protein (HSP)-27 and exhibited cytotoxic effects against gemcitabine-resistant pancreatic cancer cells. Sex-determining region Y-box 2 (SOX2) is reported to be up-regulated in other kinds of cancer cells and involved in carcinogenesis and malignancy. The aim of this study was to investigate the effects of AHCC on protein expression of SOX2 in the gemcitabine-resistant pancreatic cancer cell line KLM1-R. MATERIALS AND METHODS: AHCC was applied to KLM1-R cells and expression of SOX2 was analyzed by western blotting. RESULTS: AHCC down-regulated SOX2 in KLM1-R cells. Nanog and Oct4, co-workers of SOX2 in maintaining pluripotency, did not exhibit any significant change in protein expression. CONCLUSION: We showed the potential of AHCC to be a candidate for combinatorial therapy in anticancer drug regimens. This result suggests that the target of AHCC in expressing therapeutic efficacy was not the pluripotent cells such as cancer stem cells (CSCs) but SOX2-specific.

Active hexose-correlated compound down-regulates HSP27 of pancreatic cancer cells, and helps the cytotoxic effect of gemcitabine.

BACKGROUND/AIM: Active hexose-correlated compound (AHCC), an extract of basidiomycete mushroom, is used as health food to enhance the therapeutic effects and reduce the adverse effects of chemotherapy. Our previous proteomic analysis revealed that up-regulation of heat-shock protein 27 (HSP27) was responsible for gemcitabine resistance of pancreatic cancer cells. The aim of the present study was to investigate the effect of AHCC on the expression of HSP27 and the effect of combinatorial treatment of AHCC and gemcitabine on the gemcitabine-resistant pancreatic cancer cell line KLM1-R. MATERIALS AND METHODS: KLM1-R cells were treated with AHCC, and the expression of HSP27 as well as the cytotoxic effects of combinatorial treatment of AHCC and gemcitabine were investigated with western blotting and MTS assay, respectively. RESULTS: AHCC down-regulated HSP27 and exhibited a cytotoxic effect on KLM1-R cells. Furthermore, the cytotoxic effect of the combinatorial treatment of AHCC and gemcitabine was synergistic. CONCLUSION: This study supports the potential therapeutic benefits of combinatorial treatment of AHCC and gemcitabine for patients with pancreatic cancer.

Human pancreatic cancer cells with acquired gemcitabine resistance exhibit significant up-regulation of peroxiredoxin-2 compared to sensitive parental cells.

Gemcitabine (2'-deoxy-2'-difluorodeoxycytidine) is the only clinically effective drug for pancreatic cancer. However, high levels of inherent and acquired tumor resistance to gemcitabine lead to difficulty of chemotherapy for pancreatic cancer. We have reported on a proteomic study of gemcitabine-sensitive KLM1 and -resistant KLM1-R pancreatic cancer cells, and identified some proteins which were shown to be up-regulated in KLM1-R compared to KLM1 cells. In those proteomic studies, peroxiredoxin-2 was listed as an up-regulated protein in KLM1-R cells. Peroxiredoxin-2 is a member of a family of peroxiredoxins providing a protective role for redox damage. In this study, the expression of peroxiredoxin-2 in KLM1 and KLM1-R cells was compared. It was found that peroxiredoxin-2 was significantly up-regulated in KLM1-R cells compared to KLM1 cells (p<0.001). However, peroxiredoxin-1 expression was significantly down-regulated in KLM1-R cells (p<0.001). These results suggest that peroxiredoxin-2 is a possible candidate biomarker for predicting the response of patients with pancreatic cancer to treatment with gemcitabine.

Up-regulation of DDX39 in human pancreatic cancer cells with acquired gemcitabine resistance compared to gemcitabine-sensitive parental cells.

Intrinsic or acquired resistance of pancreatic cancer to gemcitabine (2'-deoxy-2'-difluorodeoxycytidine) is an important factor in the failure of gemcitabine treatment. Proteomic analysis of gemcitabine-sensitive KLM1 pancreatic cancer cells and -resistant KLM1-R cells identified heat-shock protein-27(HSP27) as a biomarker protein which is involved in gemcitabine resistance. However, a knock-down experiment showed that HSP27 was not the only protein implicated with gemcitabine-resistance. Finding further candidate proteins is necessary for achieving effective gemcitabine therapy for patients with pancreatic cancer. DDX39 is an Asp-Glu-Ala-Asp (DEAD)-box RNA helicase reported to be overexpressed in tumor cells, such as lung squamous cell cancer, gastrointestinal stromal tumor, urinary bladder cancer and malignant pleural mesothelioma. In urinary bladder cancer cells, overexpression of this protein is intimately bound with tumorigenesis and poor prognosis. In the present study, the expression of DDX39 in gemcitabine-sensitive KLM1 and -resistant KLM1-R cells was compared. It was found that DDX39 was significantly up-regulated in gemcitabine-resistant KLM1-R cells compared to sensitive KLM1 cells. The ratio of expression of DDX39 to that of actin was significantly up-regulated in KLM1-R cells compared to KLM1 cells (p=0.0072 by Student's t-test). These results suggest that DDX39 is a possible candidate biomarker for predicting the response of patients with pancreatic cancer to treatment with gemcitabine.