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Chikazawa K, Imai K, Ko H, Kuwata T, Konno R. Adjuvant chemotherapy after radical hysterectomy yields comparable outcomes to chemoradiation for stage IB2-IIB and IIIC1-2 cervical cancer: a single-center retrospective study. J Gynecol Oncol 2025; 36:36.e82. [PMID: 40114548 DOI: 10.3802/jgo.2025.36.e82] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 01/08/2025] [Accepted: 02/04/2025] [Indexed: 03/22/2025] Open
Abstract
OBJECTIVE This study aimed to evaluate and compare recurrence-free survival (RFS) between radical hysterectomy followed by adjuvant chemotherapy and initial chemoradiotherapy for cervical cancer at our institution. METHODS In this retrospective study, we enrolled patients diagnosed with stage IB2-IIB cervical cancer according to the International Federation of Gynecology and Obstetrics 2018 staging system, who underwent either radical hysterectomy with pelvic lymphadenectomy followed by adjuvant chemotherapy or initial concurrent chemoradiation at our institution between 2009 and 2022. RESULTS Among these patients, 74 and 110 underwent radical hysterectomy and chemoradiation, respectively. The radical hysterectomy group exhibited significantly improved RFS compared with the chemoradiation group; however, no significant difference was observed in overall survival between the groups. Cox hazard analysis for RFS showed that, among the clinical risk factors identified before the initial treatment, only parametrial invasion was statistically significant. No significant difference in RFS was observed between the radical hysterectomy group and chemoradiation group. Regarding recurrence patterns, para-aortic lymph node recurrence occurred significantly more frequently in the chemoradiation group than in the radical hysterectomy group. Postoperative ureteral injury was reported in once case and postoperative ureteral stenosis in 2 cases in the radical hysterectomy group. In contrast, vesicovaginal fistula and rectovaginal fistula were reported in one case each in the chemoradiation group. CONCLUSION Radical hysterectomy followed by adjuvant chemotherapy provided RFS outcomes comparable to those achieved with initial chemoradiotherapy for stage IB2-IIB and IIIC1-2 cervical cancer. These findings suggest that both approaches are viable, although further prospective studies are needed.
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Affiliation(s)
- Kenro Chikazawa
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, Japan.
| | - Ken Imai
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, Japan
| | - Hiroyoshi Ko
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, Japan
| | - Tomoyuki Kuwata
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, Japan
| | - Ryo Konno
- Department of Obstetrics and Gynecology, Jichi Medical University, Saitama Medical Center, Saitama, Japan
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Dong B, Zhou SF. Efficacy and safety of chemotherapy as monotherapy in patients with recurrent intermediate/high-risk factors following radical hysterectomy for stage IB-IIA cervical cancer: a single-center retrospective analysis. BMC Womens Health 2024; 24:297. [PMID: 38762459 PMCID: PMC11102237 DOI: 10.1186/s12905-024-03135-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 05/07/2024] [Indexed: 05/20/2024] Open
Abstract
OBJECTIVE The aim of this study is to explore the efficacy and safety of chemotherapy (CT) as a monotherapy in patients with recurrent intermediate/high-risk factors following radical hysterectomy for stage IB-IIA cervical cancer. METHODS A retrospective analysis was conducted on the medical records of patients diagnosed with stage IB-IIA cervical cancer who underwent radical hysterectomy at the People's Hospital of Suzhou High-tech District between 2010 and 2020. A total of 66 patients with intermediate or high-risk factors for recurrence were treated exclusively with CT. This cohort included 42 patients in the intermediate-risk group and 24 in the high-risk group. Treatment protocols consisted of 4-6 cycles of paclitaxel and cisplatin drugs for the intermediate-risk group, and 6 cycles for the high-risk group. The relapse-free survival (RFS), recurrence rates, and common CT-related adverse reactions, including bone marrow suppression, nausea and vomiting, and diarrhea, were assessed for both groups. RESULTS (1) The cumulative 3-year RFS rates for the intermediate-risk and high-risk groups were 97.3% (36/37) and 82.4% (14/17), respectively, with cumulative 5-year RFS rates of 97.1% (34/35) and 82.4% (14/17), respectively. The Log rank test revealed no significant difference between the two groups (P > 0.05), (χ² = 2.718, P = 0.099). The 5-year recurrence rates in the intermediate-risk and high-risk groups were 2.38% (1/42) and 12.50% (3/24), respectively. (2) The incidence of grade III bone marrow suppression in the intermediate-risk and high-risk groups was 21.19% (11/42) and 25.00% (6/24), respectively, while the incidence of grade IV bone marrow suppression was 11.90% (5/42) and 8.33% (2/24), respectively. There was no statistically significant difference in bone marrow suppression grades between the two groups (P > 0.05). CONCLUSION CT with paclitaxel and cisplatin, administered as monotherapy post-radical hysterectomy for stage IB-IIA cervical cancer, demonstrates satisfactory survival benefits with an acceptable safety profile. Moreover, no significant differences were observed in prognosis or adverse reactions between the different risk groups treated solely with CT.
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Affiliation(s)
- Bei Dong
- Department of Obstetrics and Gynecology, People's Hospital of Suzhou High-tech District, No. 95 of Hua-shan Road, High-tech District, Suzhou, 215000, Jiangsu Province, China
| | - Su-Fang Zhou
- Department of Obstetrics and Gynecology, People's Hospital of Suzhou High-tech District, No. 95 of Hua-shan Road, High-tech District, Suzhou, 215000, Jiangsu Province, China.
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Liu Y, He J, Liu P, Chen C. Postoperative management of FIGO 2018 stage IIA1 cervical squamous cell carcinoma with only one intermediate-risk factor: Is radiotherapy needed? Int J Gynaecol Obstet 2023; 162:1098-1105. [PMID: 37183613 DOI: 10.1002/ijgo.14839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 03/31/2023] [Accepted: 04/16/2023] [Indexed: 05/16/2023]
Abstract
OBJECTIVE To investigate whether postoperative radiotherapy is required for FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate-risk factor. METHODS This was a multicenter retrospective study. The selected patients were classified into no postoperative adjuvant therapy and postoperative radiotherapy groups. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS In total, 159 patients with no postoperative adjuvant therapy and 179 patients with postoperative radiotherapy were included, with the former group showing a lower OS but no difference in DFS. No postoperative adjuvant therapy was an independent risk factor for patient mortality. Patients were also stratified by tumor diameter: 56 patients had a tumor diameter ≤2 cm, comprising 32 patients with postoperative radiotherapy and 24 patients without (no between-group difference was found); 272 patients had a tumor diameter >2 cm, comprising 122 patients with postoperative radiotherapy and 150 patients without, with the former group showing a higher OS, and no postoperative adjuvant therapy was an independent risk factor for patient mortality. CONCLUSION For FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate-risk factor and a tumor diameter >2 cm, postoperative radiotherapy is likely beneficial to improve prognosis.
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Affiliation(s)
- Yunlu Liu
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junshen He
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ping Liu
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Chunlin Chen
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Yang XL, Yang FL, Wang N, Zhang YE, Kou LN, Wu DJ, Luo Y. A Scoring System to Select the Candidates for Adjuvant Chemotherapy Alone in High-Risk Early-Stage Cervical Cancer Patients With Pelvic Lymph Node Metastases After Surgery. Am J Clin Oncol 2023; 46:219-224. [PMID: 36877193 DOI: 10.1097/coc.0000000000000996] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2023]
Abstract
BACKGROUND The aim was to build a risk scoring system to guide the adjuvant treatment for early-stage cervical cancer patients with pelvic lymph node (LN) metastases after surgery. METHODS A cohort of 1213 early-stage cervical cancer patients with pelvic LN metastases (T1-2aN1M0) were selected from the NCI SEER database, of which 1040 patients received adjuvant external beam radiotherapy concurrent with chemotherapy (EBRT+Chemo) and 173 patients received adjuvant chemotherapy alone. The Cox regression analysis was applied to identify the risk factors associated with worse survival. The exp (β) of each independent risk factors from multivariate analysis was assigned to develop the risk scoring system. The total cohort was divided into different risk subgroups accordingly and the efficacy of different adjuvant modalities in each risk subgroups was compared. RESULTS The patients were divided into 3 risk subgroups (Low-risk: total score <7.20, Middle-risk:7.20≤ total score≤ 8.40, High-risk: total score<8.40) based on the scoring system incorporating 5 independent risk factors. The survival analysis suggested that low-risk (hazard ratio [HR]=1.046, 95% CI: 0.586-1.867; P= 0.879) and middle-risk patients (HR=0.709, 95% CI: 0.459-1.096; P =0.122) could not benefit more from EBRT+Chemo than Chemo alone. However, EBRT+Chemo remained the superiority to Chemo alone in the high-risk subgroup (HR=0.482, 95% CI: 0.294-0.791; P =0.003). CONCLUSION A risk scoring system has been built to direct the adjuvant treatment for early-stage cervical cancer patients with pelvic LN metastases after surgery, where Chemo alone was totally enough for low-risk and middle-risk patients stratified by the model while EBRT+Chemo was still recommended for patients in the high-risk subgroup.
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Affiliation(s)
| | | | - Na Wang
- Gynecology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China
| | - Yue-Er Zhang
- Department of Pain, West China Hospital, Sichuan University
| | - Ling-Na Kou
- Department of Medical Oncology, Sichuan Cancer Hospital and Institute, Chengdu
| | | | - Yi Luo
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Kim NR, Lee AJ, Yang EJ, So KA, Lee SJ, Kim TJ, Shim SH. Minimally invasive surgery versus open surgery in high-risk histologic endometrial cancer patients: A meta-analysis. Gynecol Oncol 2022; 166:236-244. [PMID: 35725657 DOI: 10.1016/j.ygyno.2022.06.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/02/2022] [Accepted: 06/08/2022] [Indexed: 01/10/2023]
Abstract
OBJECTIVE To compare the effects of minimally invasive surgery (MIS) and open surgery (OPS) on the risk of recurrence and mortality in patients with endometrial cancer (EC) of high-risk histology (grade 3 endometrioid adenocarcinoma, papillary serous carcinoma [PS], clear cell carcinoma [CC], and carcinosarcoma) using meta-analysis. MATERIAL AND METHODS We systematically reviewed published studies comparing MIS and OPS in EC patients with high-risk histology until January 2022. The endpoints were recurrence and mortality rate. Study design features that may have affected participant selection, recurrence/death detection, and manuscript publication were assessed. For pooled estimates of the effect of MIS on recurrence/mortality, the random- or fixed-effects meta-analytical models were used after assessing the cross-study heterogeneity. RESULT Nine observational studies (eight retrospective and one prospective) fulfilled our search criteria (MIS, 8877 patients; OPS, 5751 patients). The fixed-effects model-based meta-analysis indicated that MIS did not significantly increase the risk of recurrence (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.71-1.05; p = 0.13) and mortality (HR, 0.86; 95% CI, 0.79-0.93; p < 0.001) when compared with OPS. This pattern was also observed in the subgroup analyses based on the stage (early stage vs. all stage), histology (PS and CC), and MIS type (laparoscopy vs. robotic). There was no evidence of publication bias. CONCLUSION This meta-analysis of observational studies revealed that MIS did not compromise the prognosis of EC patients with high-risk histology. Well-designed randomized controlled trials could verify the results of this uncommon but deadly tumor.
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Affiliation(s)
- Nae Ry Kim
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - A Jin Lee
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Eun Jung Yang
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Kyeong A So
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Sun Joo Lee
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Tae Jin Kim
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Seung-Hyuk Shim
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
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Zhang YF, Fan Y, Zhang P, Ruan JY, Mu Y, Li JK. Cervical Cancer Recurrence and Patient Survival After Radical Hysterectomy Followed by Either Adjuvant Chemotherapy or Adjuvant Radiotherapy With Optional Concurrent Chemotherapy: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:823064. [PMID: 35311123 PMCID: PMC8931664 DOI: 10.3389/fonc.2022.823064] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 02/01/2022] [Indexed: 12/31/2022] Open
Abstract
Objective To compare cervical cancer recurrence and patient survival after radical hysterectomy followed by either adjuvant chemotherapy (AC) or adjuvant radiotherapy with or without concurrent chemotherapy (AR/CCRT). Methods We systematically searched PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov to identify studies reporting recurrence or survival of cervical cancer patients who received AC or AR/CCRT after radical hysterectomy. Data were meta-analyzed using a random-effects model, and heterogeneity was evaluated using the I2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. Results The meta-analysis included 14 non-randomized studies and two randomized controlled trials, altogether involving 5,052 cervical cancer patients. AC and AR/CCRT groups did not differ significantly in rates of total or local recurrence or mortality. Nevertheless, AC was associated with significantly lower risk of distant recurrence [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.55-0.81] and higher rates of overall survival [hazard ratio (HR) 0.69, 95%CI 0.54-0.85] and disease-free survival rate (HR 0.77, 95%CI 0.62-0.92). Conclusions AC may be an effective alternative to AR/CCRT for cervical cancer patients after radical hysterectomy, especially younger women who wish to preserve their ovaries and protect them from radiation damage. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021252518).
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Affiliation(s)
- Yu-fei Zhang
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Yu Fan
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Peng Zhang
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Jia-ying Ruan
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Yi Mu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
| | - Jin-ke Li
- Department of Gynaecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China
- *Correspondence: Jin-ke Li,
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Zhang Z, Jiang L, Bi R, Wu X, Zhu J, Ke G. Clinical Implication of Simultaneous Intensity-modulated Radiotherapy Boost to Tumor Bed for Cervical Cancer with Full-thickness Stromal Invasion. Oncologist 2022; 27:e53-e63. [PMID: 35305100 PMCID: PMC8842345 DOI: 10.1093/oncolo/oyab013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 11/18/2021] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVE The objective of this study was to retrospectively explore the clinical implications of simultaneous intensity-modulated radiotherapy (IMRT) boost to the tumor bed in cervical cancer with full-thickness stromal invasion (FTSI). PATIENTS AND METHODS Patients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB and IIA cervical cancer with confirmed FTSI were included. Patients received pelvic IMRT from a dose of 50.4 Gy in 28 fractions with (or without) a simultaneous integrated boost (SIB) to 58.8 Gy in 28 fractions for the tumor bed. The progression-free survival (PFS), overall survival (OS), and pelvic-PFS (p-PFS) were analyzed using the Kaplan-Meier method, and independent prognostic factors were explored by Cox regression analyses. RESULTS Patients without a tumor bed boost had a poor prognosis. The 5-year OS was 81.3% versus 58.3% and the 5-year PFS rates were 75.0% versus 57.6% (boost vs non-boost). The FIGO stage, pathology, adjuvant chemotherapy, and tumor bed boost were independent factors affecting both the 5-year OS and PFS. Subgroup analysis showed that the SIB group had a higher 5-year OS, PFS, and p-PFS for different stages, lymph node status, and risk groups than the non-SIB group. Recurrence occurred in 268 of 910 (29.5%) patients without SIB and 49 of 293 (16.7%) with SIB. Among patients with recurrence, 113 of 282 (40.1%) in the non-boost group compared with 14 of 51 (23.0%) patients in the boost group had a pelvic recurrence. Tumor bed boost resulted in an increase in the mean radiation dose to the intestine, rectum, and bladder, although there were no differences in the rates of acute and late toxicities between the 2 groups. CONCLUSION Tumor bed boost by external beam radiotherapy (EBRT) is an effective and safe method for patients with FTSI and risk factors. Compared with the standard prophylactic radiation, tumor bed boost by EBRT was not associated with increased acute and late toxicities.
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Affiliation(s)
| | | | - Rui Bi
- Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong-An Road, Shanghai 200032, People’s Republic of China
- Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, People’s Republic of China
| | - Xiaohua Wu
- Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong-An Road, Shanghai 200032, People’s Republic of China
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, People’s Republic of China
| | - Jun Zhu
- Corresponding author: Jun Zhu, MD, Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, People’s Republic of China.
| | - Guihao Ke
- Guihao Ke, MD, PhD, Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, People’s Republic of China.
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Qin F, Pang H, Yu T, Luo Y, Dong Y. Treatment Strategies and Prognostic Factors of 2018 FIGO Stage IIIC Cervical Cancer: A Review. Technol Cancer Res Treat 2022; 21:15330338221086403. [PMID: 35341413 PMCID: PMC8966198 DOI: 10.1177/15330338221086403] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Cervical cancer is the fourth most common malignant tumor globally in terms of morbidity and mortality. The presence of lymph node metastasis (LNM) is an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in cervical cancer patients. The International Federation of Gynecology and Obstetrics (FIGO) staging system was revised in 2018. An important revision designates patients with regional LNM as stage IIIC, pelvic LNM only as stage IIIC1, and para-aortic LNM as stage IIIC2. However, the current staging system is only based on the anatomical location of metastatic lymph nodes (LNs). It does not consider other LN status parameters, which may limit its prognostic significance to a certain extent and needs further exploration and confirmation in the future. The purpose of this review is to summarize the choice of treatment for stage IIIC cervical cancer and the effect of different LN status parameters on prognosis.
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Affiliation(s)
- Fengying Qin
- 74665Liaoning Cancer Hospital, Shenyang, Liaoning, China
| | - Huiting Pang
- 74665Liaoning Cancer Hospital, Shenyang, Liaoning, China
| | - Tao Yu
- 74665Liaoning Cancer Hospital, Shenyang, Liaoning, China
| | - Yahong Luo
- 74665Liaoning Cancer Hospital, Shenyang, Liaoning, China
| | - Yue Dong
- 74665Liaoning Cancer Hospital, Shenyang, Liaoning, China
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Wang H, Xiao R, Yang B. MiR-101-3p Suppresses Progression of Cervical Squamous Cell Carcinoma by Targeting and Down-Regulating KPNA2. Technol Cancer Res Treat 2021; 20:15330338211055948. [PMID: 34816790 PMCID: PMC8647218 DOI: 10.1177/15330338211055948] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objective We explored mechanism of microRNA-101-3p/Karyopherin α2 (KPNA2) axis in cervical squamous cell carcinoma. Methods: Bioinformatics methods were applied to identify genes for the study. Cell functional assays were implemented to examine the role of the genes in malignant progression of cervical squamous cell carcinoma. Targeting relationship between genes was verified by dual-luciferase assay. Results: MicroRNA-101-3p was lowly expressed in cervical squamous cell carcinoma, while KPNA2 was highly expressed. Dual-luciferase assay identified direct targeting relationship between microRNA-101-3p and KPNA2. Functional assays manifested that highly expressed microRNA-101-3p suppressed cervical squamous cell carcinoma cell growth by targeting KPNA2. Conclusion: Overall, microRNA-101-3p/KPNA2 axis can play an important part in progression of cervical squamous cell carcinoma.
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Affiliation(s)
- Hong Wang
- Funing People's Hospital, Jiangsu, China
| | | | - Biao Yang
- Funing People's Hospital, Jiangsu, China
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Dose Prediction Models Based on Geometric and Plan Optimization Parameter for Adjuvant Radiotherapy Planning Design in Cervical Cancer Radiotherapy. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:7026098. [PMID: 34804459 PMCID: PMC8604605 DOI: 10.1155/2021/7026098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 10/16/2021] [Indexed: 11/18/2022]
Abstract
The prediction of an additional space for the dose sparing of organs at risk (OAR) in radiotherapy is still difficult. In this pursuit, the present study was envisaged to find out the factors affecting the bladder and rectum dosimetry of cervical cancer. Additionally, the relationship between the dose-volume histogram (DVH) parameters and the geometry and plan dose-volume optimization parameters of the bladder/rectum was established to develop the dose prediction models and guide the planning design for lower OARs dose coverage directly. Thirty volume modulated radiation therapy (VMAT) plans from cervical cancer patients were randomly chosen to build the dose prediction models. The target dose coverage was evaluated. Dose prediction models were established by univariate and multiple linear regression among the dosimetric parameters of the bladder/rectum, the geometry parameters (planning target volume (PTV), volume of bladder/rectum, overlap volume of bladder/rectum (OV), and overlapped volume as a percentage of bladder/rectum volume (OP)), and corresponding plan dose-volume optimization parameters of the nonoverlapping structures (the structure of bladder/rectum outside the PTV (NOS)). Finally, the accuracy of the prediction models was evaluated by tracking d = (predicted dose-actual dose)/actual in additional ten VMAT plans. V 30, V 35, and V 40 of the bladder and rectum were found to be multiple linearly correlated with the relevant OP and corresponding dose-volume optimization parameters of NOS (regression R 2 > 0.99, P < 0.001). The variations of these models were less than 0.5% for bladder and rectum. Percentage of bladder and rectum within the PTV and the dose-volume optimization parameters of NOS could be used to predict the dose quantitatively. The parameters of NOS as a limited condition could be used in the plan optimization instead of limiting the dose and volume of the entire OAR traditionally, which made the plan optimization more unified and convenient and strengthened the plan quality and consistency.
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Ikeda M, Shida M, Shigeta S, Nagase S, Takahashi F, Yamagami W, Katabuchi H, Yaegashi N, Aoki D, Mikami M. The trend and outcome of postsurgical therapy for high-risk early-stage cervical cancer with lymph node metastasis in Japan: a report from the Japan Society of Gynecologic Oncology (JSGO) guidelines evaluation committee. J Gynecol Oncol 2021; 32:e44. [PMID: 33825359 PMCID: PMC8039172 DOI: 10.3802/jgo.2021.32.e44] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 01/19/2021] [Accepted: 01/28/2021] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVE The Japan Society of Gynecologic Oncology published the first guidelines for the treatment of cervical cancer in 2007. The aim of this research was to evaluate the influence of the introduction of the first guideline on clinical trends and outcomes of patients with early-stage cervical cancer who underwent surgery. METHODS This analysis included 9,756 patients who were diagnosed based on the pathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b and pN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Data of these patients were retrospectively reviewed, and clinicopathological trends were assessed. The influence of the introduction of the guideline on survival was determined by using a competing risk model. RESULTS For surgery cases, the estimated subdistribution hazard ratio (HR) by the competing risk model for the influence of the guideline adjusted for age, year of registration, pT classification, pN classification, histological type, and treatment methods was 1.024 (p=0.864). Following the introduction of the first guideline in 2007, for patients with lymph node metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereas that of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). For pN1 cases, the estimated subdistribution HR by the competing risk model for the influence of the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapy between CT and CCRT/RT (p=0.078). CONCLUSIONS Survival of surgical cases was not improved by the introduction of the guidelines. It is necessary to consider more effective postsurgical therapy for high-risk early-stage cervical cancer.
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Affiliation(s)
- Masae Ikeda
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Japan.
| | - Masako Shida
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Japan
| | - Shogo Shigeta
- Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan
| | - Satoru Nagase
- Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Fumiaki Takahashi
- Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai, Japan
| | - Wataru Yamagami
- Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
| | - Hidetaka Katabuchi
- Department of Obstetrics and Gynecology, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan
| | - Nobuo Yaegashi
- Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan
| | - Daisuke Aoki
- Department of Obstetrics and Gynecology, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan
| | - Mikio Mikami
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Japan
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Okugawa K, Yahata H, Sonoda K, Kodama K, Yagi H, Ohgami T, Yasunaga M, Onoyama I, Kaneki E, Asanoma K, Kobayashi H, Kato K. Evaluation of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer: a single-institution experience. Int J Clin Oncol 2021; 26:216-224. [PMID: 32880780 DOI: 10.1007/s10147-020-01778-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 08/23/2020] [Indexed: 02/02/2023]
Abstract
BACKGROUND To avoid the loss of fertility, chemotherapy should be chosen as an adjuvant treatment after trachelectomy. Our study evaluated the effectiveness and safety of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer. METHODS Our institutional review board approved this clinical study, and informed consent was obtained from each patient. We began performing abdominal trachelectomy at our institution in 2005. Deep stromal invasion (more than two-thirds) with lymphovascular space invasion, diffuse cervical invasion, skip lesions in the vagina, and lymphovascular space invasion in the cardinal ligament and vagina were defined as intermediate-risk factors, and parametrial invasion and pelvic lymph node metastasis were defined as high-risk factors. Patients who had intermediate- or high-risk factors received post-trachelectomy adjuvant treatment. The medical records and information of the patients were reviewed retrospectively. RESULTS Through January 2020, we performed 212 trachelectomies. Among the included patients, 16 and 7 patients with intermediate- and high-risk cancer, respectively, received adjuvant chemotherapy after trachelectomy (2 and 21 patients underwent abdominal modified radical trachelectomy and radical trachelectomy, respectively). Among these patients, only one (4.3%) experienced relapse and subsequent death of the disease after a median postoperative follow-up of 80 months (range 12-146 months). The 5-year survival rate was 95.5%. Chemotherapy-related life-threatening acute adverse events were not observed. Persistent ovarian dysfunction and late adverse events did not occur. One woman achieved three pregnancies, and two infants were delivered. CONCLUSION Adjuvant chemotherapy after abdominal trachelectomy could be an alternative treatment option from the aspects of effectiveness, safety, and fertility preservation.
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Affiliation(s)
- Kaoru Okugawa
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Hideaki Yahata
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kenzo Sonoda
- Gynecology Service, NHO National Kyushu Cancer Center, 3-1-1 Notame, Minami-Ku, Fukuoka, 811-1395, Japan
| | - Keisuke Kodama
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Hiroshi Yagi
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Tatsuhiro Ohgami
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Masafumi Yasunaga
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Ichiro Onoyama
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Eisuke Kaneki
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kazuo Asanoma
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Hiroaki Kobayashi
- Department of Obstetrics and Gynecology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Kiyoko Kato
- Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Zhu J, Han S. DARS-AS1 Knockdown Inhibits the Growth of Cervical Cancer Cells via Downregulating HMGB1 via Sponging miR-188-5p. Technol Cancer Res Treat 2020; 19:1533033820971669. [PMID: 33176595 PMCID: PMC7672739 DOI: 10.1177/1533033820971669] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Background: Evidence has been shown that long noncoding RNAs (lncRNAs) play an important role in the development of cervical cancer. Recently, lncRNA DARS-AS1 was shown to be dysregulated in several cancer types, but the role of DARS-AS1 in cervical cancer remains unclear. Methods: Immunofluorescence staining, flow cytometry and transwell invasion assays were used to determine proliferation, apoptosis and invasion in cervical cancer cells, respectively. The dual luciferase reporter system assay was performed to assess the interaction between DARS-AS1, miR-188-5p, and high mobility group box 1 (HMGB1) in cervical cancer cells. Results: Downregulation of DARS-AS1 markedly inhibited the proliferation and invasion of cervical cancer cells. Moreover, DARS-AS1 knockdown obviously induced the apoptosis of SiHa and HeLa cells. Meanwhile, luciferase reporter assay identified that miR-188-5p was the potential miRNA binding of DARS-AS1, and HMGB1 was the potential binding target of miR-188-5p. Mechanistic analysis indicated that downregulation of DARS-AS1 decreased the expression of HMGB1 by acting as a competitive “sponge” of miR-188-5p. Conclusion: In this study, we found that DARS-AS1 knockdown suppressed the growth of cervical cancer cells via downregulating HMGB1 via sponging miR-188-5p. Therefore, DARS-AS1 might serve as a potential target for the treatment of cervical cancer.
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Affiliation(s)
- Jinming Zhu
- Department of Oncology, Affiliated Zhongshan Hospital, Dalian University, Dalian, People's Republic of China
| | - Shichao Han
- Department of Gynecology, The 2nd Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China
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Wang W, Guo X, Dan H. α2A-Adrenergic Receptor Inhibits the Progression of Cervical Cancer Through Blocking PI3K/AKT/mTOR Pathway. Onco Targets Ther 2020; 13:10535-10546. [PMID: 33116632 PMCID: PMC7574911 DOI: 10.2147/ott.s264409] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 08/28/2020] [Indexed: 12/19/2022] Open
Abstract
Objective The study aimed to investigate the effect of α2A-adrenergic receptor (ADRA2A) on cervical cancer and the potential mechanisms of ADRA2A on phosphatidylinositol 3′-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in cervical cancer cells. Methods In our study, ADRA2A expression was evaluated by analyzing cervical cancer RNA sequencing dataset from the GEPIA. The prognostic values of ADRA2A were evaluated by Kaplan–Meier method using the Cancer Genome Atlas (TCGA) database data. In addition, the expression of ADRA2A in cervical cancer cell lines was detected by qRT-PCR and Western blot. Subsequently, the roles of ADRA2A on cell proliferation, apoptosis, migration, invasion and senescence in HeLa and SiHa cells were evaluated. Moreover, tumorigenesis in nude mice was used to investigate the role of ADRA2A in vivo. We also detected the expression changes of key factors in PI3K/Akt/mTOR pathway after overexpression and silencing of ADRA2A in HeLa and SiHa cells. Results ADRA2A expression was significantly downregulated in cervical cancer tissues and cell lines. The high expression of ADRA2A was significantly associated with a better prognosis in cervical cancer patients. ADRA2A overexpression significantly suppressed cell proliferation, migration and invasion, and promoted cell senescence and apoptosis in cervical cancer cells. On the contrary, silencing ADRA2A dramatically facilitated cell proliferation, migration and invasion, and inhibited cell senescence and apoptosis in cervical cancer cells. The expressions of p-PI3K, p-AKT and p-mTOR in cervical cancer cells were notably decreased by ADRA2A overexpression and increased by silencing ADRA2A. In addition, we also confirmed that ADRA2A overexpression could suppress the xenograft tumor growth in vivo. Conclusion Our study demonstrated that ADRA2A could suppress cell proliferation, migration and invasion, as well as promote cell senescence and apoptosis through inhibiting PI3K/Akt/mTOR pathway in cervical cancer.
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Affiliation(s)
- Weina Wang
- Health Management Center, Qingdao Sixth People's Hospital, Qingdao, Shandong 266011, People's Republic of China
| | - Xin Guo
- Department of Gynecology and Obstetrics, The People's Liberation Army Navy, The 971th Hospital, Qingdao, Shandong 266071, People's Republic of China
| | - Huiwen Dan
- Department of Gynecology and Obstetrics, The People's Liberation Army Navy, The 971th Hospital, Qingdao, Shandong 266071, People's Republic of China
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Sun X, Xu Q, Zeng L, Xie L, Zhao Q, Xu H, Wang X, Jiang N, Fu P, Sang M. Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3 Tyr705 phosphorylation. Cancer Med 2020; 9:8685-8700. [PMID: 33040485 PMCID: PMC7666735 DOI: 10.1002/cam4.3510] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 08/17/2020] [Accepted: 09/15/2020] [Indexed: 12/18/2022] Open
Abstract
Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol（RES）in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES‐mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial‐mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway.
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Affiliation(s)
- Xiaodong Sun
- Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China
| | - Qianqian Xu
- Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China
| | - Lian Zeng
- Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China
| | - Lixia Xie
- Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China
| | - Qiang Zhao
- Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China
| | - Hongxia Xu
- Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China
| | - Xuanbin Wang
- Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China
| | - Nan Jiang
- Hubei Province Hospital of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, People's Republic of China
| | - Pan Fu
- Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China
| | - Ming Sang
- Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China
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Urodynamic assessment of bladder storage function after radical hysterectomy for cervical cancer. Chin Med J (Engl) 2020; 133:2274-2280. [PMID: 32925291 PMCID: PMC7546844 DOI: 10.1097/cm9.0000000000001014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function. METHODS A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function. RESULTS Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function. CONCLUSION A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.
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Zhang J, Sun Y, Gao YJ, Zhou S. Leiomyosarcoma After Liver Transplantation Is Unrelated to Epstein-Barr Virus: A Case Report. Transplant Proc 2020; 52:2809-2812. [PMID: 32674859 DOI: 10.1016/j.transproceed.2020.06.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 06/04/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND De novo malignancy is a severe complication after liver transplantation (LT), but de novo leiomyosarcoma is extremely rare. METHODS We reported de novo leiomyosarcoma occurring after LT. The patient's status for Epstein-Barr virus was negative. The donor was a 21-year-old man with a central nervous system malignancy who underwent surgery. Three months later brain death occurred and his organs were donated. RESULTS Leiomyosarcoma in the recipient was detected shortly after LT. It progressed after minimization of immunosuppression and apatinib therapy, and the patient died of cachexia 17 months after LT. CONCLUSIONS De novo leiomyosarcoma is a rare but serious event after LT, needing comprehensive management.
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Affiliation(s)
- J Zhang
- Liver Transplant Center, Beijing Friendly Hospital, Capital Medical University, Beijing, China
| | - Y Sun
- Hepatobiliary Department and Liver Transplant Center, 302 Hospital, Beijing, 100039, China
| | - Y J Gao
- Hepatobiliary Department and Liver Transplant Center, 302 Hospital, Beijing, 100039, China.
| | - S Zhou
- Hepatobiliary Department and Liver Transplant Center, 302 Hospital, Beijing, 100039, China.
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18
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Pedone Anchora L, Carbone V, Gallotta V, Fanfani F, Cosentino F, Turco LC, Fedele C, Bizzarri N, Scambia G, Ferrandina G. Should the Number of Metastatic Pelvic Lymph Nodes be Integrated into the 2018 Figo Staging Classification of Early Stage Cervical Cancer? Cancers (Basel) 2020; 12:cancers12061552. [PMID: 32545508 PMCID: PMC7352475 DOI: 10.3390/cancers12061552] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/05/2020] [Accepted: 06/10/2020] [Indexed: 01/26/2023] Open
Abstract
Introduction: Lymph node status has become part of the new staging system for cervical cancer (CC). It has been shown that patients staged as IIIC1 had heterogeneous prognoses and, in some cases, experienced better outcomes than patients with lower stages. We evaluated the impact of the number of metastatic pelvic lymph nodes (MPLNs) among patients with stage IIIC1 cervical cancer. Methods: Survival analyses were conducted in order to identify the best cut-off prognostic value relative to the number of MPLNs. Disease free survival (DFS) was considered the main outcome. Results: 541 patients were included in the study. Eighty-nine patients were of stage IIIC1. The best prognostic cut-off value of the number of MPLNs was 2. Patients with >2 MPLNs (n > 2 group) had worse DFS compared with those having <2 (N1-2 group) (5 yr DFS: 54.7% vs. 78.1%, p value = 0.006). Multivariate analyses demonstrated that the extent of MPLNs had little impact on DFS and that replacement of IIIC1 staging with N1-2 and n > 2 grouping provided a better, statistically significant model (p value = 0.006). Discussion: Using a cut-off value of 2, the number of MPLNs could better predict prognostic outcomes within stage IIIC1 cervical cancer and have potential implications for therapeutic decision-making in the treatment of patients with stage IIIC1 CC.
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Affiliation(s)
- Luigi Pedone Anchora
- Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, 00167 Roma, Italy; (L.P.A.); (V.G.); (F.F.); (C.F.); (N.B.); (G.S.); (G.F.)
| | - Vittoria Carbone
- Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, 00167 Roma, Italy; (L.P.A.); (V.G.); (F.F.); (C.F.); (N.B.); (G.S.); (G.F.)
- Correspondence: ; Tel.: +39-333-6496669
| | - Valerio Gallotta
- Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, 00167 Roma, Italy; (L.P.A.); (V.G.); (F.F.); (C.F.); (N.B.); (G.S.); (G.F.)
| | - Francesco Fanfani
- Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, 00167 Roma, Italy; (L.P.A.); (V.G.); (F.F.); (C.F.); (N.B.); (G.S.); (G.F.)
- Istituto di Ginecologia e Ostetricia, Università Cattolica del Sacro Cuore, 00167 Roma, Italy
| | - Francesco Cosentino
- Dipartimento di Oncologia, UOC Ginecologia Oncologica, Gemelli Molise, 86100 Campobasso, Italy; (F.C.); (L.C.T.)
| | - Luigi Carlo Turco
- Dipartimento di Oncologia, UOC Ginecologia Oncologica, Gemelli Molise, 86100 Campobasso, Italy; (F.C.); (L.C.T.)
- Brest Care Unit, Mater Olbia Hospital, 07026 Olbia, Italy
| | - Camilla Fedele
- Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, 00167 Roma, Italy; (L.P.A.); (V.G.); (F.F.); (C.F.); (N.B.); (G.S.); (G.F.)
| | - Nicolò Bizzarri
- Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, 00167 Roma, Italy; (L.P.A.); (V.G.); (F.F.); (C.F.); (N.B.); (G.S.); (G.F.)
| | - Giovanni Scambia
- Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, 00167 Roma, Italy; (L.P.A.); (V.G.); (F.F.); (C.F.); (N.B.); (G.S.); (G.F.)
- Istituto di Ginecologia e Ostetricia, Università Cattolica del Sacro Cuore, 00167 Roma, Italy
| | - Gabriella Ferrandina
- Dipartimento per la salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC Ginecologia Oncologica, 00167 Roma, Italy; (L.P.A.); (V.G.); (F.F.); (C.F.); (N.B.); (G.S.); (G.F.)
- Istituto di Ginecologia e Ostetricia, Università Cattolica del Sacro Cuore, 00167 Roma, Italy
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Sakuragi N, Murakami G, Konno Y, Kaneuchi M, Watari H. Nerve-sparing radical hysterectomy in the precision surgery for cervical cancer. J Gynecol Oncol 2020; 31:e49. [PMID: 32266799 PMCID: PMC7189083 DOI: 10.3802/jgo.2020.31.e49] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 12/11/2019] [Accepted: 01/05/2020] [Indexed: 12/24/2022] Open
Abstract
Precision cancer surgery is a system that integrates the accurate evaluation of tumor extension and aggressiveness, precise surgical maneuvers, prognosis evaluation, and prevention of the deterioration of quality of life (QoL). In this regard, nerve-sparing radical hysterectomy has a pivotal role in the personalized treatment of cervical cancer. Various types of radical hysterectomy can be combined with the nerve-sparing procedure. The extent of parametrium and vagina/paracolpium excision and the nerve-sparing procedure are tailored to the tumor status. Advanced magnetic resonance imaging technology will improve the assessment of the local tumor extension. Validated risk factors for perineural invasion might guide selecting treatment for cervical cancer. Type IV Kobayashi (modified Okabayashi) radical hysterectomy combined with the systematic nerve-sparing procedure aims to both maximize the therapeutic effect and minimize the QoL impairment. Regarding the technical aspect, the preservation of vesical nerve fibers is essential. Selective transection of uterine nerve fibers conserves the vesical nerve fibers as an essential piece of the pelvic nervous system comprising the hypogastric nerve, pelvic splanchnic nerves, and inferior hypogastric plexus. This method is anatomically and surgically valid for adequate removal of the parametrial and vagina/paracolpium tissues while preserving the total pelvic nervous system. Local recurrence after nerve-sparing surgery might occur due to perineural invasion or inadequate separation of pelvic nerves cutting through the wrong tissue plane between the pelvic nerves and parametrium/paracolpium. Postoperative management for long-term maintenance of bladder function is as critical as preserving the pelvic nerves.
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Affiliation(s)
- Noriaki Sakuragi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- Department of Gynecology, Otaru General Hospital, Otaru, Japan.
| | - Gen Murakami
- Department of Anatomy II, Sapporo Medical University, Sapporo, Japan
- Division of Internal Medicine, Jikou-kai Clinic of Home Visits, Sapporo, Japan
| | - Yosuke Konno
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | | | - Hidemichi Watari
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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Kanno K, Andou M, Yanai S, Toeda M, Nimura R, Ichikawa F, Teishikata Y, Shirane T, Sakate S, Kihira T, Hamasaki Y, Sawada M, Shirane A, Ota Y. Long-term oncological outcomes of minimally invasive radical hysterectomy for early-stage cervical cancer: A retrospective, single-institutional study in the wake of the LACC trial. J Obstet Gynaecol Res 2019; 45:2425-2434. [PMID: 31502349 DOI: 10.1111/jog.14116] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 08/25/2019] [Indexed: 12/11/2022]
Abstract
AIM The objective of this study was to investigate the long-term oncological outcomes of minimally invasive radical hysterectomy (MIRH) for the treatment of early-stage cervical cancer retrospectively in the wake of the laparoscopic approach to cervical cancer (LACC) trial. METHODS A total of 109 patients with stage IA1 with lymphovascular space involvement, IA2, and IB1 cervical cancers were included in this study. The surgical and oncological outcomes were retrospectively evaluated. All patients underwent type C MIRH with a no-touch isolation technique for cervical tumor. RESULTS The median number of resected pelvic lymph nodes was 36 (range, 14-94), and 10 patients (9.2%) had positive nodes. One patient (0.9%) had positive surgical margins. Forty-six patients (42%) underwent adjuvant therapy. The median follow-up time was 73 months (range, 30-146 months). Five patients (4.6%) developed recurrent disease, and 3 patients (2.8%) died of cervical cancer. The 5-year disease-free survival and overall survival rates were 96.3% and 97.2%, respectively. A comparison between patients with tumor diameter ≤ 2 cm (n = 59) and those with tumor diameter > 2 cm (n = 50) did not identify any significant differences, with 5-year disease-free survival 96.6% versus 94.0% and 5-year overall survival 98.3% versus 96.0%, respectively. CONCLUSION In this retrospective study, MIRH with a no-touch isolation technique for stage IA to IB1 cervical cancer was a safe approach in terms of oncological outcomes. However, every surgeon who treats early-stage cervical cancer should inform each patient of the results of the LACC trial because it has an exceedingly high impact.
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Affiliation(s)
- Kiyoshi Kanno
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Masaaki Andou
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Shiori Yanai
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Mitsuru Toeda
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Ryo Nimura
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Fuyuki Ichikawa
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Yasuhiro Teishikata
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Terumi Shirane
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Shintaro Sakate
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Tomohisa Kihira
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Yoichiro Hamasaki
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Mari Sawada
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Akira Shirane
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
| | - Yoshiaki Ota
- Department of Obstetrics and Gynecology, Kurashiki Medical Center, Okayama, Japan
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Chae SH, Shim SH, Chang M, Choi AY, Kang GG, Lee SJ, Kim SN. Effect of adjuvant therapy on the risk of recurrence in early-stage leiomyosarcoma: A meta-analysis. Gynecol Oncol 2019; 154:638-650. [DOI: 10.1016/j.ygyno.2019.07.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 06/24/2019] [Accepted: 07/01/2019] [Indexed: 01/06/2023]
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Yu H, Zhang L, Li D, Liu N, Yin Y, Zhang L, Yuan L, Liu M, Sheng X. Postoperative adjuvant chemotherapy combined with intracavitary brachytherapy achieved the equivalent survival compared with concurrent chemoradiotherapy in cervical cancer patients with intermediate-risk. Jpn J Clin Oncol 2019; 49:714-718. [PMID: 31329905 DOI: 10.1093/jjco/hyz057] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 03/15/2019] [Accepted: 04/13/2019] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES The current study was aimed to evaluate the efficacy and toxicity of postoperative adjuvant chemotherapy (CT) combined with intracavitary brachytherapy (ICRT) in cervical cancer patients with intermediate-risk. METHODS We analyzed the medical records of 558 patients who were submitted to radical surgery for Stage IB-IIA cervical cancer. A total of 172 of those 558 patients were considered intermediate-risk according to the GOG criteria. Among those 172 patients, 102 were subjected to CT combined with ICRT (CT+ICRT) and the remaining 70 patients were treated with concurrent chemoradiation (CCRT). The 3-year disease free survival (DFS), overall survival (OS), and complications of each group were evaluated and analyzed. RESULTS No significant difference was observed in 3-year DFS or OS of the patients submitted to CT+ICRT and CCRT. Importantly, the frequencies of grade III to IV acute complications were significantly higher in patients submitted to CCRT than in those treated with CT+ICRT (Hematologic, P = 0.016; Gastrointestinal, P = 0.041; Genitourinary, P = 0.019). Moreover, the frequencies of grade III-IV late complications in patients treated with CCRT were significantly higher compared with CT+ICRT-treated patients (Gastrointestinal, P = 0.026; Genitourinary, P = 0.026; Lower extremity edema, P = 0.008). CONCLUSIONS Postoperative adjuvant CT+ICRT treatment achieved equivalent 3-year DFS and OS but low complication rate compared to CCRT treatment in early stage cervical cancer patients with intermediate-risk.
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Affiliation(s)
- Hao Yu
- Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China
| | - Linlin Zhang
- Department of Obstetrics and Gynecology, Shandong Maternity and Child Health Care Hospital, Jinan 250014, China
| | - Dapeng Li
- Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China
| | - Naifu Liu
- Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China
| | - Yueju Yin
- Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China
| | - Lu Zhang
- Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China
| | - Lingqin Yuan
- Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China
| | - Ming Liu
- Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China
| | - Xiugui Sheng
- Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China
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Jin G, Fan XM, Li KX, Niu SH, Zhang QY. The Association between Epidermal Growth Factor Receptor Single Nucleotide Polymorphisms and Radiochemotherapy Response in Cervical Cancer. Pathol Oncol Res 2019; 26:1255-1261. [PMID: 31254173 DOI: 10.1007/s12253-019-00690-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 06/17/2019] [Indexed: 12/11/2022]
Abstract
Emerging data reveal that epidermal growth factor receptor (EGFR) single nucleotide polymorphisms (SNPs) can act as efficacy indicators for tumor treatment. Here, the association between EGFR R497K (rs11543848) and -216G/T (rs712829) SNPs and radiochemotherapy response in cervical cancer was investigated. EGFR R497K and -216G/T genotypes were analyzed by polymerase chain reaction-ligation detection reaction in 196 cervical cancer patients receiving radiotherapy alone, or in combination with chemotherapy. Compared with the 497G/G genotype, the A/A genotype significantly increased sensitivity to radiochemotherapy treatment (adjusted OR = 0.244, 95% CI = 0.087-0.680). Sensitivity to radiochemotherapy was not significantly different in carriers of the 'T' allele than that measured for the -216G/G genotype (adjusted OR = 2.412, 95% CI = 0.856-6.979). Additionally, the 497A/A genotype conferred a reduced risk of recurrence or metastasis than did the G/G genotype (adjusted OR = 0.248, 95% CI = 0.078-0.786, P < 0.05). Moreover, carriers of the 'T' allele did not have significantly modified risk of recurrence or metastasis compared with those with the -216G/G genotype (adjusted OR = 1.027, 95% CI = 0.324-3.253). Multivariate analysis revealed an association between clinical stage and treatment response (adjusted OR = 3.575, 95% CI = 1.662-7.692) and between age and the risk of recurrence or metastasis (adjusted OR = 0.319, 95% CI = 0.148-0.691). Our results show that, in patients with cervical cancer, the R497K polymorphism is correlated with treatment response and the risk of recurrence or metastasis. The R497K SNP might be a genetic marker for prediction of radiochemotherapy response and the risk of recurrence and/or metastasis in patients with cervical cancer.
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Affiliation(s)
- Ge Jin
- Department of Gynecologic Oncology, the Fourth Hospital of Hebei Medical University, #12, Jiankang Road, Shijiazhuang, 050011, Hebei province, China
| | - Xiao-Mei Fan
- Department of Gynecologic Oncology, the Fourth Hospital of Hebei Medical University, #12, Jiankang Road, Shijiazhuang, 050011, Hebei province, China.
| | - Kui-Xiu Li
- Department of Gynecologic Oncology, the Fourth Hospital of Hebei Medical University, #12, Jiankang Road, Shijiazhuang, 050011, Hebei province, China
| | - Shu-Huai Niu
- Department of Gynecologic Oncology, the Fourth Hospital of Hebei Medical University, #12, Jiankang Road, Shijiazhuang, 050011, Hebei province, China
| | - Qian-Ying Zhang
- Department of Gynecologic Oncology, the Fourth Hospital of Hebei Medical University, #12, Jiankang Road, Shijiazhuang, 050011, Hebei province, China
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Lawal IO, Lengana T, Janse van Rensburg C, Reyneke F, Popoola GO, Ankrah AO, Sathekge MM. Fluorodeoxyglucose Positron Emission Tomography integrated with computed tomography in carcinoma of the cervix: Its impact on accurate staging and the predictive role of its metabolic parameters. PLoS One 2019; 14:e0215412. [PMID: 30998728 PMCID: PMC6472757 DOI: 10.1371/journal.pone.0215412] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Accepted: 04/01/2019] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES To determine the impact of FDG-PET/CT in the initial staging of cervical cancer among women with and without HIV and to determine the abilities of FDG-PET/CT metabolic parameters in predicting the presence of distant metastasis. METHODS We reviewed the FDG-PET/CT images of women with FIGO stage IB2 to IVA carcinoma of the cervix. We compared the FIGO stage before and after FDG-PET/CT. Maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion were determined. We compared these parameters between the HIV-infected and uninfected woman and also determined their abilities to predict the presence of distant metastasis. RESULTS 126 women, mean age 48.05 ± 11.80 years were studied. Seventy-three patients were HIV-infected. The disease was upstaged in 65 patients, 32 of which were upstaged to stage IVB. HIV-infected women were younger (43.36 ± 8.03 years versus 54.51 ± 13.12, p<0.001) and had more advanced disease (p = 0.022) compared with HIV-uninfected. In a univariate logistic regression adjusted for the FIGO stage of the disease, there were significant associations between MTV and TLG of the primary tumor and distant metastasis. SUVmax, SUVmean, MTV and TLG performed well in predicting the presence of distant metastasis with areas under the curves (AUCs) of 0.63, 0.66, 0.80 and 0.77 respectively. These performances improved after adjustment for the FIGO stage of the disease with AUCs of 0.80, 0.79, 0.84 and 0.82 for SUVmax, SUVmean, MTV and TLG respectively. CONCLUSION Inclusion of 18F-FDG-PET/CT in the pre-therapy assessment of cervical cancer improves the accuracy of staging in about half of the patients. The metabolic parameters of the primary tumor perform well in predicting the presence of distant metastases.
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Affiliation(s)
- Ismaheel O. Lawal
- Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa
| | - Thabo Lengana
- Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa
| | | | - Florette Reyneke
- Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa
| | - Gbenga O. Popoola
- Department of Epidemiology and Community Health, University of Ilorin, Ilorin, Nigeria
| | - Alfred O. Ankrah
- Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center, Groningen, The Netherlands
| | - Mike M. Sathekge
- Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa
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Zhu L, Tu H, Liang Y, Tang D. MiR-218 produces anti-tumor effects on cervical cancer cells in vitro. World J Surg Oncol 2018; 16:204. [PMID: 30314496 PMCID: PMC6186038 DOI: 10.1186/s12957-018-1506-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Accepted: 09/30/2018] [Indexed: 12/18/2022] Open
Abstract
Background As indoleamine-2,3-dioxygenase 1 (IDO1) is critical in tumor immune escape, we determined to study the regulatory mechanism of miR-218 on IDO1 in cervical cancer. Methods Real-time PCR (RT-qPCR) was carried out to measure the expression of miR-218. RT-qPCR and Western blot were performed to detect the expression of IDO1 in cervical cancer. Dual-luciferase reporter assay was used to determine the binding of miR-218 on the IDO1 3′UTR. Cell viability, apoptosis, and related factors were determined using cell counting kit-8 (CCK-8), Annexin-V/PI (propidium) assay, enzyme-linked immunosorbnent assay (ELISA), RT-qPCR, and Western blot assays after miR-218 mimics has been transfected to HeLa cervical cancer cells. Results MiR-218 was downregulated in cervical cancer. The expression of miR-218 was negatively correlated with IDO1 in cervical cancer tissues and cells. IDO1 is a direct target of miR-218. MiR-218 overexpression was found to inhibit cell viability and promoted apoptosis via activating the expression of Cleaved-Caspase-3 and to inhibit the expression of Survivin, immune factors (TGF-β, VEGF, IL-6, PGE2, COX-2), and JAK2/STAT3 pathway. Conclusion MiR-218 inhibits immune escape of cervical cancer cells by direct downregulating IDO1.
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Affiliation(s)
- Li Zhu
- Department of Gynecologic Oncology, The People's Hospital of Taojiang County, Taojiang, China
| | - Huaidong Tu
- Department of Gynecologic Oncology, The People's Hospital of Taojiang County, Taojiang, China
| | - Yanmei Liang
- Department of Gynecologic Oncology, The People's Hospital of Taojiang County, Taojiang, China
| | - Dihong Tang
- Department of Gynecologic Oncology, Hunan Cancer Hospital, No.283 Tongzipo Road, Yuelu District, Changsha, 410006, Hunan Province, China.
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