scholarly journals Erlotinib overcomes paclitaxel-resistant cancer stem cells by blocking the EGFR-CREB/GRβ-IL-6 axis in MUC1-positive cervical cancer

Oncogenesis ◽  
2019 ◽  
Vol 8 (12) ◽  
Author(s):  
Yaping Lv ◽  
Wei Cang ◽  
Quanfu Li ◽  
Xiaodong Liao ◽  
Mengna Zhan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free ◽  
Resistant Cells

AbstractCancer stem cells (CSCs) are often enriched after chemotherapy and contribute to tumor relapse. While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for the treatment of diverse types of cancer, whether EGFR-TKIs are effective against chemoresistant CSCs in cervical cancer is largely unknown. Here, we reveal that EGFR correlates with reduced disease-free survival in cervical cancer patients with chemotherapy. Erlotinib, an EGFR-TKI, effectively impedes CSCs enrichment in paclitaxel-resistant cells through inhibiting IL-6. In this context, MUC1 induces CSCs enrichment in paclitaxel-resistant cells via activation of EGFR, which directly enhances IL-6 transcription through cAMP response element-binding protein (CREB) and glucocorticoid receptor β (GRβ). Treatment with erlotinib sensitizes CSCs to paclitaxel therapy both in vitro and in vivo. More importantly, positive correlations between the expressions of MUC1, EGFR, and IL-6 were found in 20 cervical cancer patients after chemotherapy. Mining TCGA data sets also uncovered the expressions of MUC1-EGFR-IL-6 correlates with poor disease-free survival in chemo-treated cervical cancer patients. Collectively, our work has demonstrated that the MUC1-EGFR-CREB/GRβ axis stimulates IL-6 expression to induce CSCs enrichment and importantly, this effect can be abrogated by erlotinib, uncovering a novel strategy to treat paclitaxel-resistant cervical cancer.

scholarly journals TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Epigenetic Regulator ◽  
Crc Management ◽  
Disease Free ◽  
Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

scholarly journals Circulating Tumor Cells and Cancer Stem Cells: Clinical Implications in Nonmetastatic Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40856 ◽  
Author(s):  
M. Sayed ◽  
A.M. Zahran ◽  
M.S.F. Hassan ◽  
D.O. Mohamed
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Overall Survival ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Disease Free Survival ◽  
Free Survival ◽  
The Third ◽  
Disease Free

Purpose Despite the therapeutic advances, disease recurrence remains an ever-present threat to the health and well-being of breast cancer survivors. Assessment of circulating tumor cells (CTCs) and cancer stem cells (CSCs) during and after treatment may be of value in refining treatment. Methods Three 5 mL blood samples were taken from each patient: the first, at diagnosis; the second, after completion of neoadjuvant anthracyclin-based chemotherapy; and the third, a month after surgery and completion of adjuvant radiotherapy. The absolute numbers of CTCs were identified as CD45-cytokeratin+ cells. CTCs per 5 mL of blood were determined by recording all events in the whole suspension. CSCs were identified as cytokeratin+CD44+CD24-/CD45- cells. The CSCs were expressed as a percentage of CTCs. Results Univariate analysis identified the measurements of baseline CTCs and CSCs, taken after chemotherapy and one month after the cessation of radiotherapy, as prognostic factors for both four-year disease-free survival and four-year overall survival. Multivariable analysis identified the third measurement of CSCs, taken one month after the completion of radiotherapy, as the only independent prognostic factor for the four-year disease-free survival (P < 0.002, hazard ratio [HR] = 1.231, 95% CI 1.077–1.407). The initial CTC measurement was the one factor that reached significance on multivariate analysis (P < 0.03, HR 1.969, 95% CI 1.092–3.551) for the four-year overall survival. Correlation was higher between CTC and CSC counts at diagnosis ( r = 0.654, P < 0.001) than after chemotherapy ( r = 0.317, P < 0.03), because of the more rapid decrease in the mean CTC count with chemotherapy. Conclusion The CTC count could be suitable as one of the measures for monitoring response to chemotherapy, while persistence of CSC after cessation of the treatment of nonmetastatic breast cancer, except hormonal therapy when indicated, may be a reason to consider additional therapy in the future. These findings need confirmation in larger randomized trials.

Outcomes of abandoned radical hysterectomy in patients with stages IB–IIA cervical cancer found to have positive nodes during the operation

2005 ◽  
Vol 15 (3) ◽  
pp. 498-502 ◽  
Author(s):  
P. Suprasert ◽  
J. Srisomboon ◽  
K. Charoenkwan ◽  
S. Siriaungul ◽  
S. Khunamornpong ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
Radical Hysterectomy ◽  
Disease Free Survival ◽  
Pelvic Lymphadenectomy ◽  
Adjuvant Radiation ◽  
Free Survival ◽  
Number Of Patients ◽  
Extended Field ◽  
Disease Free

The objective of this study was to evaluate the outcomes of stages IB–IIA cervical cancer patients whose radical hysterectomy (RH) was abandoned for positive pelvic nodes detected during the operation compared with those found to have positive nodes after the operation. Among 242 patients with planned RH and pelvic lymphadenectomy (RHPL) for stages IB–IIA cervical cancer, 23 (9.5%) had grossly positive nodes. RH was abandoned, and complete pelvic lymphadenectomy was performed. Of these 23 patients, 22 received adjuvant chemoradiation, and the remaining 1 received adjuvant radiation. Four patients with positive para-aortic nodes were additionally treated with extended-field irradiation. When compared with 35 patients whose positive nodes were detected after the operation, there were significant differences regarding number of positive nodes and number of patients receiving extended-field irradiation. Complications in both groups were not significantly different, but the 2-year disease-free survival was significantly lower in the abandoned RH group compared with that of the RHPL group (58.5% versus 93.5%, P = 0.01). In conclusion, the survival of stages IB–IIA cervical cancer patients whose RH was abandoned for grossly positive pelvic nodes was significantly worse than that of patients whose node metastasis was identified after the operation. This is because the abandoned RH group had worse prognostic factors.

scholarly journals STIL-a novel link in Shh and Wnt signaling, endowing oncogenic and stem like attributes to colorectal cancer

2020 ◽  
Author(s):  
Tapas Pradhan ◽  
Vikas Kumar ◽  
H Evangeline Surya ◽  
R Krishna ◽  
Samu John ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Importance ◽  
Disease Free Survival ◽  
Drug Resistant ◽  
Free Survival ◽  
Over Expression ◽  
Disease Free

AbstractDiscovery of potent gene regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene, however its molecular insights and role in colorectal oncogenesis are unknown. In this study we have explored role of STIL in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). STIL silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers CD133 & CD44 and drug resistant markers Thymidylate synthase, ABCB1 & ABCG2 both in in-vitro and in-vivo CRC models. In addition, over expression of STIL mRNA was found to be associated with reduced disease free survival in CRC cases. To our surprise we observed an Shh independent regulation of stemness and drug resistant genes mediated by STIL. Interestingly, we found an Shh independent regulation of β-catenin mediated by STIL via p-AKT, which partially answers Shh independent regulatory mechanism of CSC markers by STIL. Our study suggest an instrumental role of STIL in molecular manifestation of CRC and progression.

scholarly journals Preoperative SCC-Ag as a predictive marker for the use of adjuvant chemotherapy in cervical squamous cell carcinoma with intermediate-risk factors

2020 ◽  
Author(s):  
Hong-tao Guo ◽  
Xue-han Bi ◽  
Ting Lei ◽  
Xiao Lv ◽  
Guang Yao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Distant Metastasis ◽  
Adjuvant Radiotherapy ◽  
Disease Free Survival ◽  
Free Survival ◽  
Radiotherapy Group ◽  
Pre Treatment ◽  
Disease Free

Abstract Background : For cervical cancer patients whose tumors display a combination of intermediate risk factors, postoperative radiation with or without adjuvant chemotherapy is suggested for them. However, who should be administered with adjuvant chemotherapy is unknown. The current study was designed to explore the clinical value of squamous cell carcinoma antigen (SCC-Ag) in guiding the use of adjuvant chemotherapy in cervical cancer patients. Methods : A retrospective study of 301 cervical cancer patients treated by surgery and adjuvant treatment from March 2006 to March 2016 was performed. All patients were divided into two groups according to receiving adjuvant chemotherapy or not. Overall survival (OS), disease-free survival (DFS) were compare between patients who did and did not receive adjuvant radiotherapy. Multivariate analysis was employed to detect clinical factors associated with disease-free survival, local recurrence-free survival and distant metastasis-free survival. Results: For patients with high pre-treatment SCC-Ag level, DFS and OS in adjuvant chemo-radiotherapy group were higher than that in adjuvant radiotherapy group. Besides, the rates of distant metastasis were found lower in patients who did receive adjuvant chemotherapy than those who did not. For patients with low pre-treatment SCC-Ag level, the 5-year OS and DFS were similar between groups of adjuvant chemo-radiotherapy and adjuvant radiotherapy. Multivariable analysis indicated adjuvant chemotherapy was independent predictors of DFS and distant metastasis-free survival (DMFS) in patients with high SCC-Ag level. Conclusion: SCC-Ag can serve as an indication for the administration of adjuvant chemotherapy in cervical cancer patients.

The effects of body mass index on curative radiation therapy in cervical carcinoma: An analysis of complications and survival

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16520-e16520
Author(s):  
P. H. Thaker ◽  
F. Gao ◽  
I. Zighelboim ◽  
M. A. Powell ◽  
J. S. Rader ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Cervical Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Body Mass ◽  
Disease Free Survival ◽  
Free Survival ◽  
Underweight Patients ◽  
Disease Free

e16520 Background: Recently, the rates of obese and overweight patients have increased dramatically. However, the effect of body mass index (BMI) have not been evaluated in treatment outcomes for patients with advanced stage cervical cancer receiving definitive chemotherapy and radiation therapy, and is the purpose of this study. Methods: After obtaining approval from the Washington University Human Studies Protection Office, a retrospective cohort study (n = 321) was performed on all cervical cancer patients with stage IB1 with positive lymph nodes or ≥ stage IB2 from January 1998 to January 2008. The median duration of follow up was 60 months. BMI was calculated using the National Institute of Health online BMI calculator. Main outcomes were overall survival, disease free survival, and radiation complications such as radiation enteritis/cystitis, bowel obstruction, and fistula formation. Univariate and multivariate analyses were performed, and Kaplan-Meier curves were generated. Results: Underweight patients (BMI<18.5 kg/m2) compared to normal weight (BMI = 18.5–25 kg/m2) and overweight/obese (>25 kg/m2) have a higher actuarial complication rate (p = 0.0137). Regardless of weight there is no difference in disease free survival. However, underweight patients have a significantly poorer overall survival than those patients with a higher BMI (>18.5 kg/m2) (p < 0.001). Conclusions: Underweight patients have a diminished overall survival compared to normal or obese cervical cancer patients. This is of clinical relevance when counseling underweight cervical cancer patients who will be cured of the disease with chemotherapy and radiation therapy, but have a significant risk of suffering potentially fatal complications from treatment. Further study needs to be done to elucidate this relationship further. No significant financial relationships to disclose.

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