Standard pancreatoduodenectomy versus extended pancreatoduodenectomy with modified retroperitoneal nerve resection in patients with pancreatic head cancer: a multicenter randomized controlled trial.

BACKGROUND: The extent of pancreatoduodenectomy for pancreatic head cancer remains controversial, and more high-level clinical evidence is needed. This study aimed to evaluate the outcome of extended pancreatoduodenectomy (EPD) with retroperitoneal nerve resection in pancreatic head cancer. METHODS: This multicenter randomized trial was performed at 6 Chinese high-volume hospitals that enrolled patients between October 3, 2012, and September 21, 2017. Four hundred patients with stage I or II pancreatic head cancer and without specific pancreatic cancer treatments (preoperative chemotherapy or chemoradiation) within three months were randomly assigned to undergo standard pancreatoduodenectomy (SPD) or EPD, with the latter followed by dissection of additional lymph nodes (LNs), nerves and soft tissues 270° on the right side surrounding the superior mesenteric artery and celiac axis. The primary endpoint was overall survival (OS) by intention-to-treat (ITT). The secondary endpoints were disease-free survival (DFS), mortality, morbidity, and postoperative pain intensity. RESULTS: The R1 rate was slightly lower with EPD (8.46%) than with SPD (12.56%). The morbidity and mortality rates were similar between the two groups. The median OS was similar in the EPD and SPD groups by ITT in the whole study cohort (23.0 vs. 20.2 months, P = 0.100), while the median DFS was superior in the EPD group (16.1 vs. 13.2 months, P = 0.031). Patients with preoperative CA19-9 < 200.0 U/mL had significantly improved OS and DFS with EPD (EPD vs. SPD, 30.8 vs. 20.9 months, P = 0.009; 23.4 vs. 13.5 months, P < 0.001). The EPD group exhibited significantly lower locoregional (16.48% vs. 35.20%, P < 0.001) and mesenteric LN recurrence rates (3.98% vs. 10.06%, P = 0.022). The EPD group exhibited less back pain 6 months postoperation than the SPD group. CONCLUSIONS: EPD for pancreatic head cancer did not significantly improve OS, but patients with EPD treatment had significantly improved DFS. In the subgroup analysis, improvements in both OS and DFS in the EPD arm were observed in patients with preoperative CA19-9 < 200.0 U/mL. EPD could be used as an effective surgical procedure for patients with pancreatic head cancer, especially those with preoperative CA19-9 < 200.0 U/mL.

Mycobacterium chelonae Infection After a Cat Bite: A Rare Case Report.

We describe a 62-year-old woman with a 1-month-old unhealed cat bite wound caused by Mycobacterium chelonae presenting with persistent infection despite treatment with cefazolin and amoxicillin. This is the first reported case of M. chelonae infection caused by a cat bite. Cat bites are affected by the cat's food microbiome, so clinicians should consider the cat's diet if wounds are not responding as expected to first-line therapy.

Novel end-to-side one-layer continuous pancreaticojejunostomy vs. end-to-end invaginated pancreaticojejunostomy in pancreatoduodenectomy: A single-center retrospective study.

Background and Objective: Postoperative pancreatic fistula (POPF) is the most common critical complication after pancreatoduodenectomy (PD) and is the primary reason for increased mortality and morbidity after PD. We aim to investigate the clinical significance of a novel approach, i.e., end-to-side one-layer continuous pancreaticojejunostomy, for patients with PD. Methods: The clinical data of 65 patients who underwent pancreatoduodenectomy at the Xiangya Hospital, Central South University, from September 2020 to December 2021 were retrospectively analyzed. Results: Forty patients underwent end-to-end invaginated pancreaticojejunostomy, and 25 underwent the novel end-to-side one-layer continuous pancreaticojejunostomy. No significant differences were observed in pancreatic fistula, intraperitoneal infection, intraperitoneal bleeding, reoperation, postoperative hospital stay, or perioperative death between the two groups. However, the novel end-to-side one-layer continuous pancreaticojejunostomy group had significantly shorter operation duration (32.6 ± 5.1 min vs. 8.3 ± 2.2 min, p < 0.001). The incidence of pancreatic fistula in the novel pancreaticojejunostomy group was 12%, including two cases of grade A POPF and only one case of grade B POPF. No cases of grade C POPF occurred. No deaths were observed during the perioperative period. Conclusions: The novel anastomosis method leads to a shorter operation duration than the traditional anastomosis method and does not increase postoperative complications. In conclusion, it is a simplified and feasible method for pancreatic anastomosis.

Androgen Receptors Act as a Tumor Suppressor Gene to Suppress Hepatocellular Carcinoma Cells Progression via miR-122-5p/RABL6 Signaling.

Hepatocellular carcinoma (HCC) is a malignant tumor with a high degree of malignancy and a poor prognosis. Androgen receptor (AR) has been reported to play important roles in the regulation of the progression of HCC, but the underlying mechanisms of how AR regulates HCC initiation, progression, metastasis, and chemotherapy resistance still need further study. Our study found that AR could act as a tumor suppression gene to suppress HCC cells invasion and migration capacities via miR-122-5p/RABL6 signaling, and the mechanism study further confirmed that miR-122-5p could suppress the expression of RABL6 to influence HCC cells progression by directly targeting the 3'UTR of the mRNA of RABL6. The preclinical study using an in vivo mouse model with orthotopic xenografts of HCC cells confirmed the in vitro data, and the clinical data gotten from online databases based on TCGA samples also confirmed the linkage of AR/miR-122-5p/RABL6 signaling to the HCC progression. Together, these findings suggest that AR could suppress HCC invasion and migration capacities via miR-122-5p/RABL6 signaling, and targeting this newly explored signaling may help us find new therapeutic targets for better treatment of HCC.

Bioinformatics analysis combined with experiments to explore potential prognostic factors for pancreatic cancer.

BACKGROUND: Pancreatic cancer is a common malignant tumor of the digestive tract. It has a high degree of malignancy and poor prognosis. Finding effective molecular markers has great significance for pancreatic cancer diagnosis and treatment. This study aimed to investigate DLGAP5 expression in pancreatic cancer and explore the possible mechanisms and clinical value of DLGAP5 in tumorigenesis and tumor development. METHODS: Differentially expressed genes were screened using the Gene Expression Omnibus (GEO) data set GSE16515. Gene Ontology (GO)-based functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis were performed on the corresponding proteins of the above genes using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The Kaplan-Meier Plotter database was used to analyze the relationship between differentially expressed genes and pancreatic cancer prognosis. The most prognostic gene, DLGAP5, was screened out, and the Oncomine and gene expression profiling interactive analysis (GEPIA) databases were used to analyze its expression in pancreatic cancer and other cancer tissues. The Cancer Genome Atlas (TCGA) database was used to analyze the overall survival of DLGAP5. Gene set enrichment analysis (GSEA) was performed to explore its possible molecular mechanisms in pancreatic cancer. Furthermore, the biological behavior of DLGAP5 in pancreatic cancer was verified by cell function experiments. RESULTS: A total of 201 significant upregulated differentially expressed genes and 79 downregulated genes were selected. The biological processes with significant enrichment of differential genes included cell adhesion, apoptosis, wound healing, leukocyte migration, angiogenesis. Pathways were mainly enriched in tumor-related signaling pathways such as cancer pathways, the extracellular matrix-receptor interaction pathway, and the p53 signaling pathway. DLGAP5 was significantly expressed in pancreatic cancer, and its expression level had a significant effect on patients' survival time and progression-free survival. GSEA results indicated that DLGAP5 had significantly enriched into signaling pathways such as the cell cycle, the p53 signaling pathway, and oocyte meiosis. The experimental results showed that when we knocked down the expression of DLGAP5 in pancreatic cancer cells, their proliferation ability was significantly inhibited, and their invasion and migration ability significantly decreased. CONCLUSIONS: DLGAP5 can be used as a prognostic indicator for pancreatic cancer and affect the occurrence and development of pancreatic cancer.

The miR-92a-2-5p in exosomes from macrophages increases liver cancer cells invasion via altering the AR/PHLPP/p-AKT/ß-catenin signaling.

Early studies indicated that the androgen receptor (AR) might play important roles in the regulating of the initiation and progression of hepatocellular carcinoma (HCC), but its linkage to the surrounding macrophages and their impacts on the HCC progression remain unclear. Here we found that macrophages in liver cancer might function via altering the microRNA, miR-92a-2-5p, in exosomes to decrease liver cancer cells AR expression, which might then lead to increase the liver cancer cells invasion. Mechanism dissection revealed that miR-92a-2-5p from the exosomes could target the 3'UTR of AR mRNA to suppress AR translation, altering the PHLPP/p-AKT/ß-catenin signaling to increase liver cancer cells invasion. Preclinical studies demonstrated that targeting this newly identified signaling with miR-92a-2-5p inhibitors led to suppress liver cancer progression. Together, these findings suggest that macrophages in the liver cancer tumor microenvironment may function via exosomes to regulate liver cancer progression, and targeting this newly identified macrophages/exosomes-miR-92a-2-5p/AR/PHLPP/p-AKT/ß-catenin signaling may help in the development of novel treatment strategies to better suppress liver cancer progression.

M2 Macrophages Promote HCC Cells Invasion and Migration via miR-149-5p/MMP9 Signaling.

The roles of M2 macrophages on promoting tumor progression and chemotherapy resistance have been well studied in many cancers, such as pancreatic cancer, kidney cancer and so on, but its linkage to HCC cells still remains unclear. Here we found that M2 macrophages could alter miR-149-5p to increase MMP9 expression in HCC cells and mechanism dissection revealed that miR-149-5p might directly target the 3'UTR of MMP9-mRNA to suppress its translation. The in vivo orthotopic xenografts mouse model with oemiR-149-5p also validated in vitro data. Together, these findings suggest that M2 macrophages may through altering the miR-149-5p to promote HCC progression and targeting the M2 macrophages/miR149-5P/MMP9 signaling may help in the development of the novel therapies to better suppress the HCC progression.

Explore prognostic marker of colorectal cancer based on ceRNA network.

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. With the deepening of people's understanding of CRC at the molecular level, the survival and prognosis of CRC have been significantly improved with the help of surgery, radiotherapy, and chemotherapy, molecular targeted biological therapy and early detection of diseases. The research of different disciplines and the development of multihistological analysis in recent years have proved that the occurrence and development of CRC is a complex biological process with the common action of multiple factors, which involves the huge changes of various histological levels such as the genome, transcriptome, and epigenome. At present, the abnormal expression of protein products in the transcription process has attracted more and more attention. Based on the sensitivity and timeliness of its changes, it has become a hot topic to study the occurrence and development mechanism of CRC through transcriptome changes, so as to provide markers for early diagnosis and prognosis. In recent years, competitive endogenous RNA (ceRNA) has become one of the hot topics in cancer research. The ceRNA hypothesis holds that transcripts such as long noncoding RNA can competitively bind microRNA (miRNA), thus preventing miRNA from binding to messenger RNA (mRNA) and thereby regulating the expression of mRNA. At present, the interaction mechanism of ceRNA in CRC is still unclear, and exploring its interaction relationship is of great significance to elucidate the occurrence and development mechanism of CRC. In this study, we used The Cancer Genome Atlas (TCGA) RNA - seq data of colorectal Cancer and microRnas - seq data to construct colorectal Cancer ceRNA topology network to mine key RNAs that influence the prognosis of colorectal cancer, providing potential RNA biomarkers.

C-reactive protein (CRP) promotes malignant properties in pancreatic neuroendocrine neoplasms.

OBJECTIVE: Elevated pre-operative C-reactive protein (CRP) serum values have been reported to be associated with poor overall survival for patients with pancreatic neuroendocrine neoplasms (pNEN). The aim of this study was to identify mechanisms linking CRP to poor prognosis in pNEN. METHODS: The malignant properties of pNENs were investigated using the human pNEN cell-lines BON1 and QGP1 exposed to CRP or IL-6. Analyses were performed by ELISA, Western blot, flow cytometry and immunocytochemistry as well as invasion and proliferation assays. To compare cytokine profiles and CRP levels, 76 serum samples of pNEN patients were analyzed using Luminex technology. In parallel, the expression of CRP and growth signaling pathway proteins was assessed on cell lines and paraffin-embedded primary pNEN. RESULTS: In BON1 and QGP1 cells, inflammation (exposure to IL-6) significantly upregulated CRP expression and secretion as well as migratory properties. CRP stimulation of BON1 cells increased IL-6 secretion and invasion. This was accompanied by activation/phosphorylation of the ERK, AKT and/or STAT3 pathways. Although known CRP receptors - CD16, CD32 and CD64 - were not detected on BON1 cells, CRP uptake of pNEN cells was shown after CRP exposure. In patients, increased pre-operative CRP levels (≥5 mg/L) were associated with significantly higher serum levels of IL-6 and G-CSF, as well as with an increased CRP expression and ERK/AKT/STAT3 phosphorylation in pNEN tissue. CONCLUSION: The malignant properties of pNEN cells can be stimulated by CRP and IL-6 promoting ERK/AKT/STAT pathways activation as well as invasion, thus linking systemic inflammation and poor prognosis.

Long noncoding RNA FEZF1-AS1 predicts poor prognosis and modulates pancreatic cancer cell proliferation and invasion through miR-142/HIF-1α and miR-133a/EGFR upon hypoxia/normoxia.

Nowadays, pancreatic cancer (PC) remains the most lethal tumor, partially due to the invasive and treatment-resistant phenotype induced by the extent of hypoxic stress within the tumor tissue. According to previous studies, miR-142/HIF-1α and miR-133a/EGFR could modulate PC cell proliferation under hypoxic and normoxic conditions, respectively. In the present study, FEZF1-AS1, a recently described oncogenic long noncoding RNA, was predicted to target both miR-142 and miR-133a; thus, we hypothesized that FEZF1-AS1 might affect PC cell proliferation through these two axes under hypoxic or normoxic conditions. In PC cell lines, FEZF1-AS1 acted as an oncogene via promoting PC cell proliferation and invasion through miR-142/HIF-1α axis under hypoxic condition; however, FEZF1-AS1 failed to affect the protein levels of HIF-1α and VEGF under the normoxic condition, suggesting the existence of another signaling pathway under normoxic condition. As predicted by an online tool, FEZF1-AS1 could target miR-133a to inhibit its expression; under the normoxic condition, FEZF1-AS1 exerted its effect on PC cell lines through miR-133a/EGFR axis. Taken together, FEZF1-AS1 might be a promising target in controlling the aberrant proliferation and invasion of PC cell lines.

HNF1A/CASC2 regulates pancreatic cancer cell proliferation through PTEN/Akt signaling.

Pancreatic cancer (PC) has a high mortality rate in all cancers worldwide. According to recent studies, long noncoding RNA-CASC2 is involved in the development and progression of many malignant tumors; in the present study, we demonstrated that lncRNA-CASC2 was specifically downregulated in PC tissues and cell lines, and a lower CASC2 expression in PC was related with a poorer prognosis. CASC2 suppressed PC cell proliferation. Hepatocyte nuclear factor 1 alpha (HNF1A) is a transcription factor known to regulate pancreatic differentiation and maintain the homeostasis of the endocrine pancreas. Recently, HNF1A is considered to be a possible tumor suppressor in PC. In the present study, we observed that HNF1A positively regulated CASC2 expression. Through luciferase assays, we demonstrated that CASC2 gene possessed an HNF1A-responsive element (CASC2-HNF1A RE); HNF1A could promote CASC2 expression through direct binding to CASC2-HNF1A RE. Further, PTEN/Akt signaling was involved in HNF1A regulation of CASC2. Finally, we evaluated the expression level of HNF1A in PC tissues; lower HNF1A expression was correlated with shorter overall survival in patients with PC. Taken together, these findings will shed light on the role and mechanism of HNF1A/CASC2 in regulating PC cells proliferation through PTEN/Akt signaling. CASC2 may serve as a potential therapeutic target in PC in the future.

Open surgical treatment of choledochocele: A case report and review of literature.

Choledochocele (also known as type III choledochal cyst according to Todani's classification) is a cystic dilation of the distal segment of the common bile duct protruding into the duodenal lumen. Cases are rare and the etiology remains unclear. It is usually misdiagnosed as peptic ulcer, as in the patient whose case is described here. Multislice spiral computed tomography and magnetic resonance cholangiopancreatography may be comparable to endoscopic retrograde cholangiography for diagnosis of choledochocele. Both endoscopic therapy and open surgical management are safe options, and size of the cyst plays a role in the decision-making for which approach to apply. A 50-year-old woman admitted to our hospital with upper abdominal pain caused by choledochocele with large size was successfully treated by open surgical management. We present the details of her case in this case report and discuss the recent literature on such cases and their therapeutic management.

Neuropilin-1 (NRP-1) upregulated by IL-6/STAT3 signaling contributes to invasion in pancreatic neuroendocrine neoplasms.

Although the upregulation of Neuropilin-1 (NRP-1) is associated with many solid tumors, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The aim of this study was to investigate the role of NRP-1 in improving treatment and determining the prognosis of pNEN. In this study, the expression of NRP-1 in pNEN tissue samples and pNEN cell line BON1 was analyzed by Western blot, polymerase chain reaction (PCR) and immunocytochemistry upon exposure to interleukin-6 (IL-6). Additionally, pNEN cell line BON1 was transfected with small interfering RNAs against NRP-1 or signal transducer and activator of transcription 3 (STAT3) and assessed by in vitro invasion assays. The expression of NRP-1 in pNEN tissues was markedly increased compared with adjacent normal pancreatic tissues. High NRP-1 expression was strongly correlated with tumor grades (P = .026), lymph node metastasis (P = .025), and tumor-node-metastasis stages (P = .012). Furthermore, NRP-1 downregulation notably inhibited the metastatic capacity of pNEN cells, and STAT3 knockdown was found to downregulate the expression of NRP-1. BON1 cells upregulated NRP-1 expression upon stimulation with IL-6. This was accompanied by activation/phosphorylation of the AKT and STAT3 signaling pathways. Western blot of extracts of human pNENs confirmed increased NRP-1 expression, as well as AKT/STAT3 phosphorylation in tissue of pNENs with elevated expression levels of IL-6. In conclusion, our findings suggest that NRP-1 is upregulated in pNEN and is correlated with the metastatic capacity of pNEN cells, potentially via interaction with the IL-6/STAT3 signaling pathway.

miR-125a-3p is responsible for chemosensitivity in PDAC by inhibiting epithelial-mesenchymal transition via Fyn.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and resistance to cytotoxic chemotherapy is the major cause of mortality in PDAC patients. miR-125a-3p was found to be down-regulated in PDAC cells; however, the function of miR-125a-3p in PDAC has been elusive. Here, we explored the role of miR-125a-3p in chemosensitivity in PDAC cells. METHODS: We used qRT-PCR to detect miR-125a-3p expression in two PDAC cell lines. And we measured cell viability and apoptosis by MTT assay and flow cytometry, respectively. Scratch wound healing assay and transwell invasion assay were used to test the effects of miR-125a-3p and Fyn on cell EMT process. In addition, we validated the interaction of miR-125a-3p and Fyn by dual luciferase reporter assay. qRT-PCR and western blot were used to detect the mRNA and protein expressions of E-cadhrein, N-cadhrein, Snail and Fyn. RESULTS: We found that miR-125a-3p was down-regulated in a time-dependent manner following treatment with gemcitabine in PDAC cells. Meanwhile, we found that overexpression of miR-125a-3p significantly increased chemosensitivity to gemcitabine and suppressed epithelial-mesenchymal transition (EMT) of PDAC cells. Mechanistically, miR-125a-3p directly targeted Fyn and decreased the expression of Fyn that functions to promote EMT process in PDAC. Furthermore, overexpression of Fyn could partially reverse the effects of miR-125a-3p on chemosensitivity to gemcitabine. CONCLUSION: Our study is the first to show that miR-125a-3p is responsible for chemosensitivity in PDAC and could inhibit epithelial-mesenchymal transition by directly targeting Fyn. This provides a novel potential therapeutic strategy to overcome chemoresistance in PDAC.

Krüppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2.

Pancreatic cancer (PC) is one of the most aggressive types of cancer with an extremely poor prognosis. Invasive growth and early metastasis is one of the greatest challenges to overcome for the treatment of PC. Numerous previous studies have indicated that the transcription factor Krüppel-like factor 8 (KLF8) and nuclear cofactor four and a half LIM-only protein 2 (FHL2) serve important roles in tumorigenesis and tumor progression; however, their roles in PC remain elusive. The present study revealed that KLF8 and FHL2 expression is aberrantly co-overexpressed in PC tissue samples and associated with tumor metastasis. Furthermore, a positive correlation between the expression levels of KLF8 and FHL2 was observed. Subsequently, the present study identified KLF8 as a critical inducer of epithelial-to-mesenchymal transition (EMT) and invasion. Of note, the present study demonstrated that KLF8 overexpression induced a strong increase in FHL2 expression, and subsequent promoter reporter assays determined that KLF8 directly bound and activated the FHL2 gene promoter. Furthermore, FHL2 knockdown in KLF8-overexpressing cells partially reversed the EMT and invasive phenotypes. The present study identified KLF8-induced FHL2 activation as a novel and critical signaling mechanism underlying human PC invasion.

The lncRNA XIST interacts with miR-140/miR-124/iASPP axis to promote pancreatic carcinoma growth.

Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the development and progression of many tumors. In this study, XIST was specifically upregulated in pancreatic carcinoma tissues and cell lines; a higher XIST expression was correlated to poorer clinicopathologic features. After XIST knockdown, the proliferation of PC cell lines was suppressed and cell cycle stagnated in G1 phase; XIST knockdown also reduced the protein levels of inhibitor of apoptosis-stimulating protein of p53 (iASPP) and Cyclin-dependent kinase 1 (CDK1), increased the protein level of P21, a potent CDK inhibitor. In PC cell lines, XIST and miR-140/miR-124, two tumor-associated miRNAs, could inversely regulate each other, respectively; miR-140/miR-124 could bind to XIST and the 3'UTR of PPP1R13L, respectively. XIST and miR-140/miR-124 exerted opposite effects on iASPP, CDK1, P21 and P27 proteins; whereas the effects of LV-sh-XIST on the indicated protein levels could be partially reversed by miR-140 and/or miR-124 inhibitor. In PC tissues, miR-140 and miR-124 expression was down-regulated, iASPP and CDK1 mRNA expression was up-regulated. XIST positively correlated with iASPP and CDK1, inversely correlated with miR-140 and miR-124, respectively. Taken together, our data indicated that XIST might be an oncogenic lncRNA that promoted proliferation of PC cell line through inhibiting miR-140/miR-124 expression and promoting cell cycle-related factor expression, and could be regarded as a therapeutic target in human pancreatic carcinoma.

Chinese herb derived-Rocaglamide A is a potent inhibitor of pancreatic cancer cells.

Pancreatic cancer ranks No.1 in mortality rate worldwide. This study aims to identify the novel anti-pancreatic cancer drugs. Human pancreatic carcinoma cell lines were purchased from ATCC. CPE-based screening assay was used to examine the cell viability. Patient derived tumor xenografts in SCID mice was established. The Caspase-3 and 7 activities were measured using the Caspase Glo 3/7 Assay kit. Soft agar colony formation assay was used to evaluate the colony formation. Wound healing assay was employed to determine the cell migration. We screened a Chinese herbal product library and found three "hits" that kill cancer cells at nanomolar to micromolar concentrations. One of these compounds, rocaglamide, was found to be potent inhibitors of a wide spectrum of pancreatic cancer cell lines. Furthermore, Rocaglamide reduced the tumor size in a patient-derived pancreatic cancer xenograft mouse model without noticeable toxicity in vivo. Rocaglamide also inhibits pancreatic cancer cell migration and invasion. In conclusion, these data support that Rocaglamide may be a promising anti-pancreatic cancer drug.

KLF8 knockdown triggered growth inhibition and induced cell phase arrest in human pancreatic cancer cells.

BACKGROUND: The transcription factor Krüppel-like factor 8 (KLF8) plays an important role in tumor development and growth, but its role in pancreatic cancer (PC) is not clear. METHODS: KLF8 expression in human PC cell lines and tumor tissues was measured by quantitative real-time polymerase chain reaction and Western blot analyses. The effects of lentivirus mediated knockdown of KLF8 on proliferation and growth in Panc-1 pancreatic cancer cells were examined. RESULTS: KLF8 was overexpressed in 5 pancreatic cancer cell lines and in samples from patients with PC. In Panc-1 cells, KLF8 knockdown inhibited cell proliferation, tumorigenicity, and induced G2/M phase arrest. KLF8 knockdown suppressed PC tumor growth in nude mice model. Western blot analysis showed that KLF8 knockdown in Panc-1 cells down-regulated the expression of CDK1/CDC2, cyclin B1, and cyclin D1 and up-regulated the expression of p21, and p27. CONCLUSIONS: Overexpression of KLF8 may contribute to the progression of pancreatic cancer, and downregulation of KLF8 expression by lentivirus-delivered shRNA is a novel therapeutic approach for PC.

The clinical utility of CA125/MUC16 in pancreatic cancer: A consensus of diagnostic, prognostic and predictive updates by the Chinese Study Group for Pancreatic Cancer (CSPAC).

The prognosis for pancreatic cancer (PC) is poor; however, the timely and accurate treatment of this disease will significantly improve prognosis. Serum biomarkers involve non-invasive tests that facilitate the early detection of tumors, predict outcomes and assess responses to therapy, so that the patient can be continuously monitored and receive the most appropriate therapy. Studies have reported that cancer antigen (CA)125 [also known as mucin 16 (MUC16)] has functional significance in the tumorigenic, metastatic and drug resistant properties of PC. Our aim was to use this biomarker in the diagnosis, detection of metastasis, prognosis and in the monitoring of the treatment effects of PC. Members of the Chinese Study Group for Pancreatic Cancer (CSPAC) reviewed the literature on CA125/MUC16 and developed an objective consensus on the clinical utility of CA125/MUC16 for PC. They confirmed the role of CA125/MUC16 in tumorigenesis and the progression of PC, and recommended monitoring CA125/MUC16 levels in all aspects of the diagnosis and treatment of PC, particularly those that involve the monitoring of treatments. In addition, they suggested that the combination of other biomarkers and imaging techniques, together with CA125/MUC16, would improve the accuracy of the clinical decision-making process, thereby facilitating the optimization of treatment strategies. Periodic clinical updates of the use of CA125/MUC16 have been established, which are important for further analyses and comparisons of clinical results from affiliates and countries, particularly as regards the in-depth biological function and clinical translational research of this biomarker.