STAT1-mediated inhibition of FOXM1 enhances gemcitabine sensitivity in pancreatic cancer

The aim of the present study was to investigate the survival and prognostic factors of patients who were with advanced esophageal squamous cell carcinoma (ESCC) and developed an esophageal fistula. The data from 221 patients with advanced ESCC developed esophageal fistula from January 2008 to December 2017 at the Harbin Medical University Cancer Hospital was retrospectively analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by the Cox proportional hazard models. The median survival time after a diagnosis of the esophageal fistula was calculated using the Kaplan–Meier method. We found that the pathogens infected by patients are common bacteria in nosocomial infection. Besides, the incidence rate of esophagomediastinal fistula was the highest (54.2%) in the lower third of the esophagus. Kaplan–Meier analysis revealed a median survival time of 11.00 months and a median post-fistula survival time of 3.63 months in patients who developed esophageal fistula in advanced esophageal cancer. In the univariate analysis, gender, therapies for ESCC before the development of fistula, type of esophageal fistula, treatment of esophageal fistula and hemoglobin (Hb) level were the factors with significant prognostic value. Gender, type of esophageal fistula and Hb level were identified as independent prognostic factors in further multivariate analysis. In summary, our study demonstrated that several factors are significantly related to patients with esophageal fistula and should be concerned about in clinical practice.

show abstract

“…P<0.05 was considered statistically significant. Statistical analysis was conducted using SPSS 18.0 [18].…”

Section: Discussionmentioning

confidence: 99%

Survival and prognostic factors of patients with esophageal fistula in advanced esophageal squamous cell carcinoma

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The expression of USP5 in pancreatic cancer tissues was detected using IHC. The sections were processed for immunohistochemical staining as previously reported 11 . The 4-μm-thick sections were deparaffinized before heated in citrate buffer (0.01 M).…”

Section: Methodsmentioning

confidence: 99%

“…Total proteins were harvested from cultured cells as described previously 11 . Proteins were separated by 10% SDS-polyacrylamide gel electrophoresis and then transferred to PVDF membranes.…”

Section: Methodsmentioning

confidence: 99%

Ubiquitin specific peptidase 5 enhances STAT3 signaling and promotes migration and invasion in Pancreatic Cancer

Lian¹,

Liu²,

Guan³

et al. 2020

J. Cancer

Self Cite

View full text Add to dashboard Cite

Purpose: Ubiquitin specific peptidase 5 (USP5) has been reported to promote the progression of several malignant tumors. It may affect cancer development via modulating cell cycle and colony formation. In pancreatic cancer, the biological function of USP5, especially in migration and invasion remains unclear. Methods: USP5 protein expression levels in primary pancreatic cancer and lymph node metastasis tissues were detected using immunohistochemistry (IHC). χ 2 test, Kaplan-Meier analysis, univariate and multivariate analyses were used to evaluate the relationship between USP5 expression and clinicopathological feature. RT-qPCR were carried out to quantitate the mRNA expression levels of USP5 in pancreatic cancer cell lines. CCK8 and Colony formation assay were performed to prove how USP5 works in proliferation. Evaluation of tumor metastasis was made by Transwell and wound healing assay. EMT and STAT3 signaling related markers were detected by western blot. Results: (1) USP5 protein expression levels were related to tumor differentiation, CEA and CA19-9 level. (2) Univariate and multivariate analyses showed that high USP5 expression is an unfavorable prognostic factor for pancreatic cancer. Kaplan-Meier analysis directly indicated that patients with high USP5 expression had shorter overall survival. (3) Increased USP5 expression is related to pancreatic cancer in both proliferation and metastasis. (4) USP5 was proved to mediate STAT3 signaling in pancreatic cancer cells. Conclusions: The results suggest that USP5 is highly expressed and might have clinical significance for pancreatic cancer patients. High USP5 expression promotes both progression and metastasis by activating STAT3 signaling. Thus, USP5 might be a potential target in pancreatic cancer treatment.

show abstract

“…The Forkhead box protein M1 (FOXM1) is an oncogenic transcription factor and its elevated expression is associated with gemcitabine resistance in patients with pancreatic cancer 24 . Expression of the FOXM1 gene did not significantly alter in the GemMIA-R3 cell line compared to the parental line, but CM03 treatment results in some downregulation (log 2 FC = − 0.52).…”

Section: Genementioning

confidence: 99%

A G-quadruplex-binding compound shows potent activity in human gemcitabine-resistant pancreatic cancer cells

Ahmed

Marchetti

Ohnmacht

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Gemcitabine is a drug of choice in the treatment of human pancreatic cancer. chemo-resistance to this drug is common and has been attributed to a variety of distinct mechanisms, involving > 100 genes. A recently developed small-molecule G-quadruplex ligand, the trisubstituted naphthalene diimide compound CM03, has previously been shown to have equivalent potency to gemcitabine in the pancreatic cancer cell line MIA PaCa-2. We report here on cell lines of increased resistance to gemcitabine that have been generated from this line, with the most resistant having 1,000fold reduced sensitivity to gemcitabine. These resistant lines retain nM sensitivity to CM03. The molecular basis for the retention of potency by this G-quadruplex ligand has been examined using whole transcriptome data analysis with RnA-seq. this has revealed that the pattern of pathways down regulated by CM03 in the parental MIA PaCa-2 cell line is largely unaffected in the gemcitabineresistant line. the analysis has also shown that the expression patterns of numerous genes involved in gemcitabine sensitivity are down regulated in the resistant line upon CM03 treatment. These results are supportive of the concept that G-quadruplex small molecules such as CM03 have potential for clinical use in the treatment of gemcitabine-resistant human pancreatic cancer. Pancreatic cancer is among the 12 most common cancers in the UK and the USA, with 9,921 new cases in the UK in 2015 1 and 57,600 estimated new cases in the USA in 2020 2. 458,918 new cases were reported worldwide in 2018 3. Pancreatic ductal adenocarcinoma (PDAC: ca 85% of cases), is the most common form, and is also one of the most intractable of cancers to treatment. It has a bleak prognosis that has barely changed in over 20 years, with < 5% of patients surviving for five years 4-7 .The standard chemotherapy for PDAC has been the nucleoside analogue gemcitabine (Fig. 1a), which produces a modest improvement in mean survival of, typically, 2-3 months 8-10. Initial responses are almost invariably followed by the rapid onset of chemo-resistance 11-14. This has been attributed to, for example, changes in nucleoside transporter expression 15 , or in gemcitabine metabolising enzymes such as cytidine deaminase 16,17. The complexity of the underlying mechanisms of gemcitabine resistance in PDAC is increasingly apparent and over 100 genes and multiple pathways may be involved 18-24. We have recently reported that several small-molecule naphthalene diimide derivatives 25,26 , notably the trisubstituted compound CM03 27 , are potent inhibitors of cancer cell growth, with CM03 (Fig. 1b) having a GI 50 value of ca 11 nM in the PDAC cell lines PANC-1 and MIA PaCa-2. RNA-seq methodology has shown that CM03 targets a number of genes involved with PDAC initiation and progression in these cell lines, and also has significant anti-cancer activity in in vivo xenograft and genetic models for the disease. The mode of action of CM03 involves the stabilisation of genomic quadruplex DNA structures 28 and as a consequenc...

show abstract

STAT1-mediated inhibition of FOXM1 enhances gemcitabine sensitivity in pancreatic cancer

Cited by 39 publications

References 56 publications

Survival and prognostic factors of patients with esophageal fistula in advanced esophageal squamous cell carcinoma

Survival and prognostic factors of patients with esophageal fistula in advanced esophageal squamous cell carcinoma

Ubiquitin specific peptidase 5 enhances STAT3 signaling and promotes migration and invasion in Pancreatic Cancer

A G-quadruplex-binding compound shows potent activity in human gemcitabine-resistant pancreatic cancer cells

Contact Info

Product

Resources

About