Oncology Intelligence

Endometrial Cancer
11:00 PM|Elshaikh, Mohamed A.; Vance, Sean; Gaffney, David K.; Biagioli, Matthew; Jhingran, Anuja; Jolly, Shruti; Kidd, Elizabeth; Lee, Larissa J.; Li, Linna; Moore, David H.; Rao, Gautam G.; Wahl, Andrew O.; Williams, Ned L.; Yashar, Catheryn M.; Small, William Jr; Expert Panel on Radiation Oncology–Gynecology:|American Journal of Clinical Oncology - Most Popular Articles|Labels: endometrial cancer
imageObjectives: In women with endometrial carcinoma (EC), tumor recurrences tend to occur in the 2- to 3-year period following surgical staging. Management of disease recurrence in EC poses significant challenges. These patients represent a heterogenous group where histologic subtypes, previous adjuvant management, interval since completion of adjuvant therapy, and size and site(s) of disease recurrence all have important implications on salvage therapies and prognosis. No randomized controlled trials have been published to determine optimal management in this group of patients. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients. Methods: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Results: Five clinical variants were developed to address common scenarios in the management of women with recurrent EC. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches with numerical ratings. Conclusions: In combining available medical literature and expert opinions, this manuscript may serve as an aid for other practitioners in the appropriate management of women with recurrent EC.
Thursday, September 22, 2016 5:13 PM|Onclive Articles|Labels: mTOR, endometrial cancer
Combining the diabetes drug metformin with everolimus and letrozole resulted in a clinical benefit rate of 60% in women with advanced or recurrent endometrioid endometrial cancer. 
Monday, September 19, 2016 6:00 PM|Molly S. Daniel, Karen H. Lu|Seminars in Oncology|Labels: endometrial cancer
This review article discusses the diagnosis and management of hereditary ovarian cancer and hereditary uterine cancer. The key recommendations highlighted are: All women with high grade non-mucinous epithelial ovarian cancer should be offered at least BRCA1 and BRCA2 genetic testing. The care of women with BRCA-associated ovarian cancer should be tailored to their mutation status. Risk reducing bilateral salpingo-oophorectomy is recommended for women with BRCA1/2 mutations. Women with endometrial cancer should be assessed for the possibility of Lynch syndrome.
Friday, September 16, 2016 3:10 AM|Jingfang Zou, Liangli Hong, Chaohuan Luo, Zhi Li, Yuzhang Zhu, Tianliang Huang, Yongneng Zhang, Huier Yuan, Yaqiu Hu, Tengfei Wen, Wanling Zhuang, Bozhi Cai, Xin Zhang, Jiexiong Huang, Jidong Cheng|Cancer Science|Labels: endometrial cancer
Metformin is an oral biguanide commonly used for the treating type II diabetes and has recently been demonstrated to possess anti-proliferative properties that can be exploited for the prevention and treatment of a variety of cancers. The mechanisms underlying this effect have not been fully elucidated. Our study demonstrated a marked loss of AMP-activated protein kinase (AMPK) phosphorylation and nuclear FOXO1 protein in estrogen-dependent endometrial cancer (EC) tumors compared to normal control endometrium. Metformin treatment suppressed EC cell growth in time-dependent manner in vitro; this effect was cancelled by co-administration of an AMPK inhibitor, compound C. Metformin decreased FOXO1 phosphorylation and increased FOXO1 nuclear localization in Ishikawa and HEC-1B cells, with non-significant increase on FOXO1 mRNA expression. Moreover, compound C blocked the metformin-induced changes of FOXO1 and its phosphorylation protein, suggesting that metformin upregulated FOXO1 activity by AMPK activation. Similar results were obtained after treatment with insulin. In addition, transfection with siRNA for FOXO1 cancelled metformin-inhibited cell growth, indicating that FOXO1 mediated metformin to inhibit EC cell proliferation. A xenograft mouse model further revealed that metformin suppressed HEC-1B tumor growth, accompanied by the down-regulated ki-67 and up-regulated AMPK phosphorylation and nuclear FOXO1 protein. Taken together, these data provide a novel mechanism of anti-neoplastic effect for metformin through the regulation of FOXO1, and suggest that AMPK-FOXO1 pathway may be a therapeutic target to the development of new anti-neoplastic drugs. This article is protected by copyright. All rights reserved.
Tuesday, September 13, 2016 11:38 PM|Wan Kyu Eo, Sanghoon Kwon, Suk Bong Koh, Min Jeong Kim, Yong Il Ji, Ji Young Lee, Dong Soo Suh, Ki Hyung Kim, Heung Yeol Kim|Journal of Cancer|Labels: endometrial cancer

Objective: We assessed the prognostic implications of preoperative lymphocyte-monocyte ratio (LMR) in patients with endometrial cancer (EC).

Methods: We retrospectively examined the LMR as a prognostic variable in a cohort of 255 patients with EC who underwent surgical resection. Patients were categorized into two groups according to the LMR (LMR-low and LMR-high) using cutoff points determined by receiving operator characteristic (ROC) curve analysis. The primary objective was to correlate the LMR to clinicopathological factors; the secondary objective was to determine the survival significance of the LMR in patients with EC.

Results: Using data from the entire cohort, the most discriminative LMR cutoff value selected on the ROC curve was 3.28 for both disease-free survival (DFS) and overall survival (OS). The LMR-low and LMR-high groups included 33 (12.9%) and 222 patients (87.1%), respectively. The 5-year DFS rates in the LMR-low and LMR-high groups were 64.5 and 93.9% (P < 0.0001), respectively, and the 5-year OS rates in the two groups were 76.7 and 96.5% (P < 0.0001), respectively. On multivariate analysis, we identified histologic grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and LMR levels as the strongest prognostic factors affecting DFS (P = 0.0037, P < 0.0001, and P < 0.0001, respectively), and FIGO stage and the LMR as the strongest prognostic factors predicting OS (P < 0.0001 and P < 0.0001, respectively).

Conclusion: The LMR is an independent prognostic factor for both DFS and OS after surgical resection, and it provides additional prognostic value beyond standard clinicopathological parameters.

Tuesday, September 6, 2016 3:00 PM|Cancer|Cancer via|Comments|Labels: PI3K, endometrial cancer, clinical trial
CONCLUSIONSThe antitumor activity noted with the use of a dose of 40 mg of apitolisib daily was limited by tolerability, especially in diabetic patients. Patients with PI3K pathway mutations may have derived enhanced benefit from apitolisib. Cancer 2016. © 2016 American Cancer Society. (Source: Cancer)
Wednesday, August 31, 2016 11:00 PM|Li, Li-li; Fan, Jiang-tao; Li, Da-hai; Liu, Yan|International Journal of Gynecological Cancer - Current Issue|Labels: endometrial cancer
imageObjective: The purpose of this study was to explore the effects of a small interfering RNA (siRNA) targeting YKL-40 on the proliferation and invasion of endometrial cancer (EC) HEC-1A cells. Methods: We used an siRNA targeting a sequence in YKL-40 (si-YKL-40) to transfect HEC-1A cells. Quantitative real-time polymerase chain reaction assay was performed to investigate the mRNA levels of YKL-40. MTT, migration, and invasion assays were performed to identify the effects of si-YKL-40 on the proliferation, migration, and invasive abilities of the HEC-1A cells. Results: mRNA expression of YKL-40 was down-regulated in HEC-1A cells after transfection with si-YKL-40 (P < 0.05). The proliferation, migration, and invasive abilities of HEC-1A cells were inhibited by siRNA (P < 0.05). Conclusions: YKL-40 targeting siRNA specifically blocks the activity of YKL-40 in human EC HEC-1A cells, resulting in tumor suppression. This indicates that YKL-40 might serve as a potential small molecule target in the treatment of EC.
Friday, August 26, 2016 1:20 PM|Elsevier|JournalTOCs API - Biochemical and Biophysical Research Communications (50 articles)|Labels: endometrial cancer

LncRNA FER1L4 suppresses cancer cell proliferation and cycle by regulating PTEN expression in endometrial carcinoma

Biochemical and Biophysical Research Communications, Vol. , No. (2016) pp. -
Publication date: 16 September 2016 Source:Biochemical and Biophysical Research Communications, Volume 478, Issue 2 Author(s): Qiao Qiao, Hong Li Background Dysregulated long non-coding RNAs (lncRNAs) might exert key roles in pathways associated with endometrial carcinoma (EC) development. This study aims to investigate the new role of lncRNA FER1L4 in EC pathogenesis due to its correlation with phosphatase and tensin homolog (PTEN), one important indicator of EC progression. Methods Real time PCR was performed to detect the expression of FER1L4 in thirty paired EC samples and two EC cell lines. Plasmid containing FER1L4 was transfected into HEC-50 cells with a relative lower level of FER1L4 expression, followed which PTEN expression and Akt phosphorylation were measured by western blotting. Cell proliferation was analyzed through MTT and colony-formation assays, while cell cycle and apoptosis were determined by flow cytometry. Results FER1L4 showed significantly downregulation in EC tissues compared to control, which was positively correlated with decreased PTEN expression. Moreover, FER1L4 could promote PTEN expression and inhibit Akt phosphorylation. Additionally, a significant decrease of cell proliferation was observed in FER1L4 overexpressing cells, along with cell cycle arrest at G0/G1 phase and increased proportion of apoptotic cells. Conclusion FER1L4 not only showed downregulation in EC tissues and cells, but also regulated PTEN expression and Akt signaling, which might contribute to its inhibition on cell proliferation. This study might provide a new potential therapeutic target for EC treatment.

Wednesday, July 27, 2016 11:11 AM|AUMIPHIN, J., CROCHET, P., KNIGHT, S., CARCOPINO, X., CRAVELLO, L., BOUBLI, L., AGOSTINI, A.|Anticancer Research recent issues|Labels: endometrial cancer

Aim: To study outcomes of patients diagnosed with endometrial carcinoma (EC) after histological analysis of endometrial resections retrieved during operative hysteroscopy performed for a presumed benign lesion. Patients and Methods: A retrospective study was conducted using medical records of patients who underwent operative hysteroscopy for a presumed benign lesion with a final diagnosis of EC between January 1994 and April 2014 in two tertiary academic centers. Results: A total of 29 patients were selected. International federation of gynecology and obstetrics (FIGO) classification was distributed as follows: 16 stages IA, 7 stages IB, 4 stages II and 2 stages III. Peritoneal cytology was positive in one case (stage IIIA). Median follow-up was 4.2 years (range=0.3-20.51). Two deaths were observed and were attributed to endometrial cancer. Conclusion: Operative hysteroscopy does not appear to influence stage of EC nor cause retrograde seeding of EC for 27/29 (93%) patients. For 2 patients, the impact of operative hysteroscopy remains uncertain.

Thursday, June 30, 2016 11:00 PM|Jiang, Yan; Wang, Ning; Yin, Duo; Li, Yong Kang; Guo, Li; Shi, Li Ping; Huang, Xiao|International Journal of Gynecological Cancer - Current Issue|Labels: endometrial cancer
imageObjective: The purpose of the study was to examine whether miR-887-5p could be used as a diagnostic marker for endometrial cancer. Methods: In the first stage, differentially expressed serum micro-RNAs (miRNAs) in the sera of 50 healthy subjects and 50 patients with endometrial cancer were screened by performing Solexa sequencing. In addition, differential expression of these serum miRNAs in endometrial cancer tissues and adjacent normal tissues from 3 patients with endometrial cancer was examined. Comparison of the differentially expressed miRNAs showed that miR-887-5p was significantly expressed in the sera of patients with endometrial cancer as well as in endometrial cancer tissues. In the second stage, quantitative reverse transcription polymerase chain reaction was performed to verify the levels of miR-887-5p in the sera of 20 patients with endometrial cancer and of 20 healthy subjects. Results: Expression of miR-887-5p was significantly increased in the sera of patients with endometrial cancer (P < 0.05) compared with that in the sera of healthy subjects. Receiver operating characteristic curve analysis showed that the area of miR-887-5 under the ROC curve for endometrial cancer diagnosis was 0.728, specificity was 0.60, sensitivity was 0.95, and 95% confidence interval was 0.563-0.892. Besides, with strict screen, we eliminate the other risk factors of endometrial cancer in our healthy donors and cancer patients. Statistical analysis of data obtained for patients in the 2 stages by using SPSS version 17.0 indicated that menarche age (P = 0.47, P = 0.49), body mass index (P = 0.313, P = 0.749), history of hypertension (P = 0.517, P = 0.058), and diabetes (P = 0.205, P = 0.507) had no correlation with endometrial cancer. Conclusion: Serum miR-887-5p levels were significantly increased in patients with endometrial cancer. Therefore, serum miR-887-5p could be used as a potential biomarker for endometrial cancer.
Thursday, June 30, 2016 11:00 PM|Kost, Edward R.; Valente, Philip T.; Lynch, Barnard A.; Krishnegowda, Naveen K.; Hertz, Alexandria M.; Hall, Kevin L.; Riddle, Nicole D.; Tekmal, Rajeshwar R.|International Journal of Gynecological Cancer - Current Issue|Labels: endometrial cancer
imageObjectives: Approximately 3% to 5% of endometrial cancers (EC) are associated with Lynch syndrome (LS). The clinical characteristics and prevalence of LS have not been well studied in the US Hispanic population. Hispanics are the largest and fastest growing ethnic minority group in the United States. We sought to characterize the demographics, tumor characteristics, and prevalence of loss of mismatch repair (MMR) protein expression in a large Hispanic population with EC. Methods: From January 1, 2005, to August 1, 2012, 83 women of Hispanic ethnicity diagnosed with EC 50 years and younger were identified. Clinical and pathologic data were abstracted from the electronic medical record. Tumor studies included immunohistochemistry of MLH1, MSH2, MSH6, and PMS2 and methylation of the MLH1 promoter. Results: Ninety-five percent of patients were overweight or obese. The mean body mass index was 40.1 kg/m2, 75% had irregular menses, 36% had diabetes, 46% were nulliparous, and 95% had endometrioid histology. Thirteen patients (15.7%) had tumor MMR deficiency due to a presumed germline mutation (9 MSH6, 3 MSH2, and 1 MLH1). The pattern of MMR protein loss was consistent with the expected binding properties of the MMR heterodimer complexes. No significant difference was found in clinical or pathological variables between patients with and without MMR deficient tumors. Conclusions: The prevalence of molecular findings consistent with LS was at least as high as other populations of varied geography, race, and ethnicity. We found no reliable factors to include body mass index, family history, synchronous tumors, or pathologic tumor features to serve as triage markers for which ECs should be screened for MMR protein loss. Our findings support a recommendation for universal screening of ECs utilizing 2-antibody testing with MLH1 promoter methylation testing as indicated up to 60 years or older. Our recommendations should be generalizable to other Hispanic populations in the Southern United States.
Thursday, June 30, 2016 11:00 PM|Qin, Yun; Yu, Zhizhi; Yang, Jiaxin; Cao, Dongyan; Yu, Mei; Wang, Yanhong; Shen, Keng|International Journal of Gynecological Cancer - Current Issue|Labels: endometrial cancer
imageObjective: This study aimed to evaluate the efficacy and safety of oral progestin treatment for early-stage endometrial cancer. Methods: We conducted a systematic review and meta-analysis of the proportions from observational studies. Original studies were selected if patients with early-stage endometrial cancer, especially those of reproductive age, were treated with oral progestin. We conducted searches on studies listed in MEDLINE, EMBASE, and Cochrane that were published through June 2014, and relevant articles were also searched. The methodological quality of the included studies was assessed using the Newcastle-Ottawa quality assessment scale. Funnel plots and metaregression analyses were used to assess bias. Results: The final sample included 25 articles involving 445 patients. Based on a random-effects model, patients achieved a disease regression rate of 82.4% (95% confidence interval [CI], 75.3%–88.7%), a relapse rate of 25.0% (95% CI, 15.8%–35.2%), a pregnancy rate of 28.8% (95% CI, 22.5%–35.5%), and a live birth rate of 19.6% (95% CI, 12.8%–27.4%). Body weight gain, liver dysfunction, and abnormal blood coagulation test results were the most common treatment-related adverse effects. Only 2 disease-related deaths were reported during the follow-up duration. Conclusions: Based on the present systematic review and meta-analysis, oral progestin treatment is feasible and safe for patients of reproductive age.
Monday, June 27, 2016 10:52 AM|MIYAHARA, D., KATSUTA, T., MAEHARA, M., TAKAHASHI, Y., FUKAGAWA, S., MIYATA, K., KIYOSHIMA, C., YOTSUMOTO, F., ANAN, H., MIYAMOTO, S.|Anticancer Research recent issues|Labels: endometrial cancer

Background: Endometrial cancer (EC) has a poor prognosis due to drug resistance. Patients and Methods: We evaluated the safety and efficacy of adjuvant combination chemotherapy with docetaxel plus cisplatin ((DP) docetaxel, 70 mg/m2; cisplatin, 60 mg/m2; every 28 days) in EC patients at intermediate-risk (IR) or high-risk (HR) for recurrence. Results: Sixty-four patients diagnosed with EC were enrolled. Stage-I, -II, -III and -IV disease was noted in 23, 7, 28 and 6 patients, respectively. Histopathological analyses revealed that 56, 3, 1 and 4 patients had endometrioid, serous, clear-cell or "other" types of carcinoma. Grade-3/4 hematologic toxicities were found at 80% and 95% in patients in IR and HR groups, respectively. In IR and HR groups, mean progression-free (PFS) survival was 69.5 and 29.5, while overall survival (OS) was 59.6 and 47.5 months, respectively. Conclusion: DP may be clinically safe and useful treatment for EC.

Wednesday, June 15, 2016 3:00 PM|Cancer|Cancer via|Comments|Labels: endometrial cancer
Worldwide, the incidence of endometrial carcinoma (EC) is rapidly increasing, and the highest disease burden is reported in North America and Western Europe. Although the prognosis remains good for patients with are diagnosed with early stage EC, for those with recurrent or metastatic disease, the options are few, and the median overall survival is short. It is imperative to gain a greater understanding of all aspects of EC, limit its effect on scarce health care resources and, more importantly, prevent this cancer from significantly impacting future generations of women. An exciting new era of endometrial cancer research and clinical management has begun that incorporates biologically and clinically relevant genomic and clinicopathologic parameters. Continued collaborative research effort...
Monday, March 28, 2016 5:30 AM|Current Cancer Therapy Reviews|MedWorm: Cancer Therapy|Comments|Labels: endometrial cancer, uterine cancer
Uterine epithelial cancers are the most common type of gynecologic cancer in the United States. The American Cancer Society estimated 53,000 new cases of uterine cancers in 2014 with 8,600 deaths from advanced or recurrent cases, 99% of which are endometrial cancer. The 5-year survival rate of low-stage, low-grade endometrioid adenocarcinoma is greater than 90%. In contrast, advanced stage endometrioid adenocarcinomas and Type II (serous and carcinosarcoma) endometrial cancers have a much poorer prognosis, with the 5-year survival rate of advanced stage uterine carcinosarcoma as low as 9%. Together, these endometrial cancers with poor prognoses comprise almost half of all cases in the US, creating a significant medical obstacle for management. The authors present a review of endometrial ca...
Saturday, February 28, 2015 11:00 PM|Young, Melissa Rasar; Higgins, Susan A.; Ratner, Elena; Yu, James B.; Mani, Sheida; Silasi, Dan-Arin; Azodi, Masoud; Rutherford, Thomas; Schwartz, Peter E.; Damast, Shari|International Journal of Gynecological Cancer - Most Popular Articles|Labels: endometrial cancer
imageObjective: The aim of this study was to evaluate outcomes of patients with stage III endometrial adenocarcinoma treated with surgery followed by adjuvant chemotherapy and vaginal cuff brachytherapy. Methods: We retrospectively identified 83 patients treated for 1988 International Federation of Gynecology and Obstetrics (FIGO) stage III endometrial adenocarcinoma at our institution between 2003 and 2010. All patients underwent comprehensive surgical staging. Adjuvant therapy was carboplatin and paclitaxel for 6 cycles and vaginal cuff brachytherapy. For analysis, patients were grouped into type I (FIGO grade 1–2 endometrioid histology, n = 41) or type II (FIGO grade 3, clear cell or papillary serous histology, n = 42) disease. Forty-three patients (52%) had node-positive disease, with similar node-positive rates for type I (n = 21, 51.2%) and type II (n = 22, 52.4%). Results: The median follow-up was 38.6 months. There were no isolated vaginal failures. The estimated 3-year disease-free survival (DFS) and overall survival (OS) for type I versus type II were 92.4% versus 58.0% (P = 0.001) and 97.2% versus 65.8% (P = 0.002), respectively. The 3-year DFS and OS for node negative versus node positive were 85.0% versus 63.6% (P = 0.02) and 84.2% versus 78.0% (P = 0.02), respectively. Associations between type I histology and node-negative disease with improved DFS and OS persisted on multivariate analysis. Conclusions: Our institutional approach of adjuvant chemotherapy and vaginal cuff brachytherapy for stage III endometrial cancer seemed acceptable for patients with low-risk histology or node-negative disease. In contrast, higher rates of failure among those with high-risk histology and/or node-positive disease support intensification of therapy in these subsets.