Advances in precision therapy of low-grade serous ovarian cancer: A review.

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer that accounts for approximately 6% to 10% of serous ovarian cancers. The clinical treatment of LGSOC is similar to that of high-grade serous ovarian carcinoma, however, its clinical and molecular characteristics are different from those of high-grade serous ovarian carcinoma. This article reviews the research on gene diagnosis, surgical treatment, chemotherapy, and biological therapy of LGSOC, providing reference for clinical diagnosis and treatment of LGSOC. Surgery is the cornerstone of LGSOC treatment and maximum effort must be made to achieve R0 removal. Although LGSOC is not sensitive to chemotherapy, postoperative platinum-based combination chemotherapy remains the first-line treatment option for LGSOC. Additional clinical trials are needed to confirm the clinical benefits of chemotherapy and explore new chemotherapy protocols. Hormone and targeted therapies may also play important roles. Some patients, particularly those with residual lesions after treatment, may benefit from hormone maintenance therapy after chemotherapy. Targeted therapies, such as MEKi, show good application prospects and are expected to change the treatment pattern of LGSOC. Continuing to further study the genomics of LGSOC, identify its specific gene changes, and combine traditional treatment methods with precision targeted therapy based on second-generation sequencing may be the direction for LGSOC to overcome the treatment bottleneck. In future clinical work, comprehensive genetic testing should be carried out for LGSOC patients to accumulate data for future scientific research, in order to find more effective methods and drugs for the treatment of LGSOC.

Retraction Notice to: lncRNA GAS5 Inhibits Cell Migration and Invasion and Promotes Autophagy by Targeting miR-222-3p via the GAS5/PTEN-Signaling Pathway in CRC.

[This retracts the article DOI: 10.1016/j.omtn.2019.06.009.].

lncRNA GAS5 Inhibits Cell Migration and Invasion and Promotes Autophagy by Targeting miR-222-3p via the GAS5/PTEN-Signaling Pathway in CRC.

Colorectal cancer (CRC) is a frequently occurring lethal disorder with heterogeneous outcomes and drug responses. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) play a critical role in carcinogenesis. Hence, the aim of this study was to investigate the role of lncRNA growth arrest-specific 5 (GAS5) in CRC cells via mediation of the microRNA-222-3p (miR-222-3p)/GAS5/phosphatase and tensin homolog (PTEN)-signaling pathway. HCT116 and SW480 cells were collected and treated with small interfering (si)-lncRNA GAS5, overexpressing (oe)-lncRNA GAS5, miR-222-3p mimic, miR-222-3p inhibitor, or si-lncRNA GAS5 + miR-222-3p mimic. The miR-222-3p level and mRNA and protein levels of GAS5, Beclin1, light-chain 3B (LC3B), PTEN, and Akt were detected. Besides, cell migration, invasion, and apoptosis as well as acidic vesicular organelles (AVOs) were examined respectively. Xenografts in nude mice were also performed to detect tumorigenesis in vivo. Results suggested that the downregulation of lncRNA GAS5 decreased the expressions of Beclin1, LC3B, and PTEN. When treated with oe-lncRNA GAS5 or miR-222-3p inhibitor, HCT116 and SW480 cells exhibited suppressed invasion and migration abilities and increased apoptotic cells and autophagosome and AVO activities. Moreover, overexpression of GAS5 inhibited the tumorigenesis of CRC cells in vivo. Taken together, lncRNA GAS5 upregulated the expression of PTEN by functioning as a competing endogenous RNA (ceRNA) of miR-222-3p, thus inhibiting CRC cell migration and invasion and promoting cell autophagy.

Prognostic and predictive value of long non-coding RNA GAS5 and mircoRNA-221 in colorectal cancer and their effects on colorectal cancer cell proliferation, migration and invasion.

BACKGROUND: LncRNA and microRNA play an important role in the development of human cancers; they can act as a tumor suppressor gene or an oncogene. LncRNA GAS5, originating from the separation from tumor suppressor gene cDNA subtractive library, is considered as an oncogene in several kinds of cancers. The expression of miR-221 affects tumorigenesis, invasion and metastasis in multiple types of human cancers. However, there's very little information on the role LncRNA GAS5 and miR-221 play in CRC. Therefore, we conducted this study in order to analyze the association of GAS5 and miR-221 with the prognosis of CRC and preliminary study was done on proliferation, metastasis and invasion of CRC cells. In the present study, we demonstrate the predictive value of long non-coding RNA GAS5 (lncRNA GAS5) and mircoRNA-221 (miR-221) in the prognosis of colorectal cancer (CRC) and their effects on CRC cell proliferation, migration and invasion. METHODS: One hundred and fifty-eight cases with CRC patients and 173 cases of healthy subjects that with no abnormalities, who've been diagnosed through colonoscopy between January 2012 and January 2014 were selected for the study. After the clinicopathological data of the subjects, tissue, plasma and exosomes were collected, lncRNA GAS5 and miR-221 expressions in tissues, plasma and exosomes were measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The diagnostic values of lncRNA GAS5 and miR-221 expression in tissues, plasma and exosomes in patients with CRC were analyzed using receiver operating characteristic curve (ROC). Lentiviral vector was constructed for the overexpression of lncRNA GAS5, and SW480 cell line was used for the transfection of the experiment and assigned into an empty vector and GAS5 groups. The cell proliferation, migration and invasion were tested using a cell counting kit-8 assay and Transwell assay respectively. RESULTS: The results revealed that LncRNA GAS5 was upregulated while the miR-221 was downregulated in the tissues, plasma and exosomes of patients with CRC. The results of ROC showed that the expressions of both lncRNA GAS5 and miR-221 in the tissues, plasma and exosomes had diagnostic value in CRC. While the LncRNA GAS5 expression in tissues, plasma and exosomes were associated with the tumor node metastasis (TNM) stage, Dukes stage, lymph node metastasis (LNM), local recurrence rate and distant metastasis rate, the MiR-221 expression in tissues, plasma and exosomes were associated with tumor size, TNM stage, Dukes stage, LNM, local recurrence rate and distant metastasis rate. LncRNA GAS5 and miR-221 expression in tissues, plasma and exosomes were found to be independent prognostic factors for CRC. Following the overexpression of GAS5, the GAS5 expressions was up-regulated and miR-221 expression was down-regulated; the rate of cell proliferation, migration and invasion were decreased.

Effect of inhibiting Beclin-1 expression on autophagy, proliferation and apoptosis in colorectal cancer.

The present study aimed to investigate the molecular mechanisms and effect of Beclin-1 on autophagy, proliferation and apoptosis in the colorectal cancer (CRC) HCT116 and SW620 cells. Beclin-1 was silenced by RNA interference (RNAi) in HTC116 and SW620 cells. Reverse transcription-polymerase chain reaction and western blot were used to measure the expression of Beclin-1. The percentage of apoptotic cells was analyzed by cell counting kit-8 (CCK-8) and flow cytometry (FCM). Cell cycle and cell proliferation were analyzed by FCM and the MTT assay. The present study created 3 groups in the two cell lines, consisting of the targeting siRNA (TS) group, in which Beclin-1 was partially silenced, non-specific siRNA (NS) group and control group (CG; without transfection). By siRNA transfection, the mRNA and protein level of Beclin-1 in the TS group were significantly inhibited compared with the NS group and CG (P<0.05). After 0, 24, 48 and 72 h, the survival rate of the cells in the TS group was significantly decreased compared with the survival rate of the cells in the NS group and CG, as detected by CCK-8 methods (P<0.05). FCM and MTT results showed the apoptotic rate of the cells in the TS group was significantly decreased compared with the rate in the NS group and CG (P<0.05), and the proliferation of the cells in the NS group was evidently increased compared with the CG. In conclusion, Beclin-1 played an important role in regulating autophagy, proliferation and apoptosis in HCT116 and SW620 cells. The inhibition of Beclin-1 by RNAi suppressed the autophagic activity and proliferation, but promoted apoptosis in CRC cells. Beclin-1 was the new target of gene therapy for CRC.

[Effects of increased body mass index upon laparoscopic radical rectal surgery and its clinical efficacy].

OBJECTIVE: To assess the feasibility, the safety and short-term outcomes of laparoscopic radical rectal surgery for rectal cancer patients with increased body mass index (BMI) . METHODS: Retrospectively data reviews were conducted for 405 consecutive patients undergoing laparoscopic surgery for rectal cancer from June 2008 to June 2012. They were classified as normal-weight (NW, BMI 18.6-22.9 kg/m(2), n = 165), overweight (OW, BMI 23.0-24.9 kg/m(2), n = 125), and obese (OB, BMI ≥ 25.0 kg/m(2), n = 115)groups according to the categories as proposed by 2007 Chinese Obesity Surgery Treatment Guidelines. The differences of oncologic, intraoperative and postoperative status, postoperative complications, number of resected lymph nodes and short-term survival rates were compared among three groups. The data were analyzed by χ(2) or Fisher exact test. The Mann-Whitney U test or analysis of variance (one-way ANOVA) was used for parametric comparisons. The survival curve was drawn by Kaplan Meier method and the survivals of 3 groups were by the Log-rank test. RESULTS: The comorbidity of patients in the NW and OW groups were less than that in the OB group(27.9% (46/165) and 30.4% (38/125) vs 47.0% (54/115), χ(2) = 12.066, P < 0.05). No significant difference existed among the groups in terms of conversion rate (9.1% (15/165), 10.4% (13/125) and 12.2% (14/115)), the rate of postoperative complications (20.6% (34/165), 21.6% (27/125) and 24.3% (28/115) ), intraoperative volume of blood loss ((105 ± 30), (110 ± 25) and (115 ± 45) ml), first flatus( (2.8 ± 1.2), (2.9 ± 1.1) and (3.1 ± 1.4) d), postoperative hospital stays ((13.7 ± 5.5), (14.3 ± 7.5) and (14.1 ± 8.5) d, all P > 0.05), and the mean number of retrieved lymph nodes(P > 0.05). While the operation duration in the OB group were longer than that in the NW and OW groups ((250 ± 35) vs (205 ± 20) and (210 ± 30) min, F = 7.216, P < 0.05) . And 368 patients (90.9%) were followed up for a median of 24 months(2-48 months). As for survival curves, no significant difference existed among three groups (P > 0.05). CONCLUSIONS: It is both safe and feasible for obese patients with increased BMI to undergo laparoscopic radical rectal cancer. And there is no effect upon immediate survival.

[Analysis of factors associated with lateral lymph node metastasis in mid and low rectal cancer].

OBJECTIVE: To investigate the factors associated with lateral lymph node metastasis in middle and low rectal cancer. METHODS: Clinical data of 203 patients with middle and low rectal cancer (within 10 cm from anal verge) undergoing lateral lymph node dissection in the Affiliated Cancer Hospital, Xinjiang Medical University between June 2004 to June 2010, were analyzed retrospectively. Logistic regression analysis was used to screen the associated factors. RESULTS: The total number of harvested lateral lymph node was 3349, and average number was 17 per case. The number of positive lateral lymph node was 221, and the lymph node metastasis ratio was 6.6%(221/3349). Univariate analysis showed that age, family history, tumor length, gross type of tumor, histological type, differentiation, depth of invasion, invasion of circumference, serum CEA, tumor thrombus and upper lymph node metastasis were associated with rectal cancer metastasis(P<0.05). Multivariate analysis showed that age, histological type, infiltration depth, gross type, differentiation degree and upper lymph node metastasis were the independent risk factors of the lateral lymph node metastasis in middle and low rectal cancer(P<0.05). CONCLUSION: For patients who is young, or with poorly differentiated cancers, infiltrative type, T4 cancer, or those with upper lymph node metastasis, lateral lymph resection may be indicated because of high risk of lateral node metastasis.

[Evaluation of short-term efficacy and safety after laparoscopic resection for mid-low rectal cancer].

OBJECTIVE: To investigate the safety, feasibility and short-term efficacy of laparoscopic surgery in patients with middle-low rectal cancer. METHODS: From January 2008 to January 2010, a total of 108 patients with middle-low rectal cancer at Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University were divided into 2 groups by different treatments: laparoscopic resection group (LR, n = 63) and conventional open resection group (OR, n = 45). The choice of two surgical options was based on patient's desire. The outcomes of two patient groups with radical surgery were prospectively evaluated. RESULTS: Seven cases were converted into open surgery from the laparoscopic group. The operative durations in the LR and OR groups were (246 ± 57) min and (229 ± 53) min respectively (P > 0.05). The laparoscopic group had a lesser amount of blood loss during surgery ((51 ± 20) ml vs (110 ± 41) ml, P < 0.05). The time needed for the recovery of gastrointestinal functions in the laparoscopic group was significantly shorter than that in the open surgery group ((3.0 ± 0.8) d vs (3.7 ± 1.3) d, P < 0.05). In terms of the length of specimen, the range of radical surgery and the rate of complication, no significant difference were found between two groups (all P > 0.05). The numbers of dissected lymph nodes were 13 and 12 cases respectively (P > 0.05). No instance of incision implantation, local recurrence or short-term death was found in neither group. There was 2 cases with lung metastasis in the LR group and 2 cases with the metastasis of liver and lung in the OR group. CONCLUSION: As a safe, feasible, effective and mini-invasive with similar radical resection and satisfactory short-term outcomes, laparoscopic surgery for low-middle rectal cancer has better prospects in the future.

[Clinical multivariate regression analysis of local recurrence following curative surgery for rectal cancer].

OBJECTIVE: To investigate the clinicopathologic factors related to local recurrence following curative surgery for rectal cancer and explore the ways to improve the efficacies. METHODS: A total of 257 post-operative cases of rectal cancers from January 1995 to December 2002 were recruited. And the relation of each clinicopathologic characteristic and local post-operative recurrence was retrospectively investigated. The clinicopathologic factors and follow-up data were analyzed by uni and multi-factorial regression model by logistic regression. RESULTS: The total local recurrence rate of rectal cancer after radical operation was 18.7%, 75.0% (36/48) within 2 years and 95.8% (45/48) within 3 years, the median time was 14.6 months (range: 2-63). Univariate analysis showed that age, Dukes' stage, lymph node metastasis and level of CEA were significantly associated with the local post-operative recurrence (P<0.05). Multivariate analysis showed that age and lymph node metastasis were closely related with the local post-operative recurrence (P<0.05). CONCLUSION: Lymph node metastasis and age are very important prognostic factors for the local post-operative recurrence. It is possible to improve the prognosis of rectum cancer by making an early diagnosis and offering a scientific standard therapy.