Extraordinary Response of Metastatic Pancreatic Cancer to Chemotherapy / 대한소화기암학회지

A 58-year-old woman presented with right flank and back pain for one month. After undergoing an abdominal computed tomography (CT), she was referred to our hospital. The abdominal CT showed a hypodense pancreatic tail mass with multiple retroperitoneal lymph node metastases. Positron emission tomography-computed tomography (PET-CT) scan showed high 18F-FDG uptake in pancreatic tumor and enlarged lymph nodes. Endoscopic ultrasound fine needle aspiration (EUS-FNA) revealed adenocarcinoma, which stained strongly in hENT1 (human equilibrative nucleoside transporter 1) on immunohistochemistry. She received gemcitabine 1,000 mg/m² + nanoparticle albumin-bound paclitaxel 125 mg/m² as a palliative chemotherapy. Follow-up abdominal CT and PET-CT after 4 cycles of chemotherapy showed that both pancreatic mass and the metastatic retroperitoneal lymph nodes were nearly disappeared. We report a case of 58-year-old female with metastatic pancreatic cancer who had a dramatic response to palliative chemotherapy (gemcitabine plus nanoparticle albumin-bound paclitaxel).

Functional characterization of human equilibrative nucleoside transporter 1

Equilibrative nucleoside transporters (ENTs), which facilitate cross-membrane transport of nucleosides and nucleoside-derived drugs, play an important role in the salvage pathways of nucleotide synthesis, cancer chemotherapy, and treatment for virus infections. Functional characterization of ENTs at the molecular level remains technically challenging and hence scant. In this study, we report successful purification and biochemical characterization of human equilibrative nucleoside transporter 1 (hENT1) in vitro. The HEK293F-derived, recombinant hENT1 is homogenous and functionally active in proteoliposome-based counter flow assays. hENT1 transports the substrate adenosine with a K of 215 ± 34 µmol/L and a V of 578 ± 23.4 nmol mg min. Adenosine uptake by hENT1 is competitively inhibited by nitrobenzylmercaptopurine ribonucleoside (NBMPR), nucleosides, deoxynucleosides, and nucleoside-derived anti-cancer and anti-viral drugs. Binding of hENT1 to adenosine, deoxyadenosine, and adenine by isothermal titration calorimetry is in general agreement with results of the competitive inhibition assays. These results validate hENT1 as a bona fide target for potential drug target and serve as a useful basis for future biophysical and structural studies.

p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: p21-activated kinases (PAKs) are involved in cytoskeletal reorganization, gene transcription, cell proliferation and survival, and oncogenic transformation. Therefore, we hypothesized that PAK expression levels could predict the sensitivity of pancreatic cancer cells to gemcitabine treatment, and PAKs could be therapeutic targets. MATERIALS AND METHODS: Cell viability inhibition by gemcitabine was evaluated in human pancreatic cancer cell lines (Capan-1, Capan-2, MIA PaCa-2, PANC-1, Aspc-1, SNU-213, and SNU-410). Protein expression and mRNA of molecules was detected by immunoblot analysis and reverse transcription polymerase chain reaction. To define the function of PAK4, PAK4 was controlled using PAK4 siRNA. RESULTS: Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment. Immunoblot analysis of signaling molecules reported to indicate gemcitabine sensitivity showed higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1), a well-known predictive marker for gemcitabine activity, in the resistant cell lines. Knockdown of PAK4 using siRNA induced the upregulation of hENT1. In resistant cell lines (Capan-2, PANC-1, and SNU-410), knockdown of PAK4 by siRNA resulted in restoration of sensitivity to gemcitabine. CONCLUSION: PAK4 could be a predictive marker of gemcitabine sensitivity and a potential therapeutic target to increase gemcitabine sensitivity in pancreatic cancer.

Expression of hENTl and ERCC1 genes in tumor tissues non-small cell lung cancer

OBJECTIVE@#To investigate the expression of hENTl and ERCC1 genes in tumor tissues non-small cell lung cancer (NSCLC).@*METHODS@#Fresh non-small lung cancer specimens were transplanted into nude mice. Twenty mice were randomized into two groups: experimental group receiving gemcitabine plus cisplatin and control group receiving 0.9% physiological saline. The expressions of hENTl and ERCC1 mRNA in tumor tissue were detected by real-time fluorescent quantitative PCR. The volume of tumor, the weight of nude mice and tumor volume were respectively measured and calculated 2-3 times per week. Tissue samples were collected from NSCLC mice treated with gemcitabine plus carboplatin.@*RESULTS@#The histological examination showed that many tumor cells were well preserved in nude mice. The rate of transplanted tumor cells was 86.7%. The concomitant treatment study showed that the rate of TV, RTV, T/C in GEM + DDP group was the lowest. LBP + DOC, DDP + DOC obviously influenced the body weight. Compared with NS group, DDP group, GEM group, the survival period and the level of hENTl of DDP+GEM group increased obviously, the level of ERCC1 decreased significantly (P<0.05).@*CONCLUSIONS@#The expression of hENT1 and ERCC1 genes in tumor tissues were closely correlated with the response to chemotherapy and prognosis of patients with NSCLC treated with gemcitabine plus cisplatin.