Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endometrial carcinoma is the most common gynecological malignancy among women worldwide. Although treatment for EC has improved with the introduction of Paclitaxel (Tax) chemotherapy, the majority of patients will develop resistance to the treatment, leading to poor prognosis. One of the causes of chemoresistance is the increased ability to undergo autophagy. In this study, we identified that miR-218 was significantly down-regulated in Tax-resistant EC cells compared to the non-drug resistant cell lines, and overexpression of miR-218 sensitized paclitaxel resistant EC cells to paclitaxel. Moreover, we demonstrated that miR-218 directly binds to the 3'-UTR of HMGB1 gene. HMGB1 was upregulated in paclitaxel resistant EC cells, it mediated autophagy and contributed to chemotherapy resistance in endometrial carcinoma in vitro. HMGB1-mediated autophagy could be suppressed by miR-218 overexpression in Tax resistant EC cells. In summary, we determined the targeting role of miR-218 to HMGB1 and the regulation of miR-218 on the HMGB1-mediated cell autophagy during chemotherapy resistance in endometrial carcinoma cells. These results reveal novel potential role of miR-218 against chemotherapy resistance during the treatment of endometrial carcinoma.
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PMID:MiR-218 inhibits HMGB1-mediated autophagy in endometrial carcinoma cells during chemotherapy. 2626 43

Carboplatin is an alkylating anti-neoplastic drug used in various cancers especially ovarian cancer, germ cell tumors, endometrial cancer besides others. We present a case of acute autoimmune hemolytic anemia during Carboplatin infusion in a patient previously exposed to the drug, resulting in the death of the patient. Published reports of Carboplatin induced autoimmune hemolytic anemia suggest these are usually nonfatal and improve after discontinuation of the drug. Fatal autoimmune hemolysis from Carboplatin has not been reported to the best of our knowledge. A 77-year-old Caucasian lady with history of endometrial adenocarcinoma was receiving treatment with a combination of Carboplatin and Paclitaxel for recurrent adenocarcinoma presenting as a pelvic mass. She tolerated similar chemotherapy previously, except for mild side effects. During her fifth cycle of chemotherapy with Carboplatin, she suddenly collapsed in the infusion center. Despite aggressive treatment, she expired within seven hours. A direct Coomb's test was found to be positive. Carboplatin dependent antibody was also detected. She was felt to have had a Carboplatin-induced fatal hemolytic anemia. Acute autoimmune hemolytic anemia with Carboplatin is rare but could be a devastating complication. A sudden drop in hemoglobin during Carboplatin infusion should alert clinicians of this extremely fatal possibility.
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PMID:Carboplatin Induced Fatal Autoimmune Hemolytic Anemia: First Reported Case. 2914 1

Paclitaxel is the first microtubule-stabilizing agent identified and considered to be the most significant advance in chemotherapy of the past two decades. It is considered one of the most widely used antineoplastic agents with broad activity in several cancers including breast cancer, endometrial cancer, non-small-cell lung cancer, bladder cancer, and cervical carcinoma. It is also used for treating AIDS-related Kaposi sarcoma as a second line treatment. This comprehensive profile of paclitaxel gives overview of nomenclature, formulae, elemental analysis, appearance, application and uses. In addition, mechanism of action and resistance, different dosage forms and methods of drug preparation are elaborated. Moreover, the physicochemical properties involving X-ray powder diffraction pattern, drug solubility, melting point, differential scanning calorimetry, and stability were summarized. Furthermore, method of drug analysis including compendial, spectrophotometric, and chromatographic was discussed.
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PMID:Paclitaxel. 3102 18

In endometrial cancer (EC), adrenal metastases are rare indicating advanced disease. We report an unusual presentation of EC with solitary adrenal metastases at the time of diagnosis and provide with an updated literature review. A 68-year-old woman was referred with postmenopausal bleeding of several weeks' duration. Imaging revealed a heterogenous uterine mass and bilateral malignant adnexal masses. Hysteroscopy, endometrial biopsies, and radiological guided biopsies of the adrenal masses confirmed poorly differentiated EC. A PET-CT reported both adrenal metastases being hypermetabolic and suspicious for malignancy. The patient received six neoadjuvant chemotherapy cycles with Carboplatin and Paclitaxel. A repeated CT scan confirmed size reduction for both primary tumour and metastases. The adrenal metastases were no longer PET-avid on repeat PET-CT scan. The patient received a course of hormonal treatment and as per adrenal MDT, she underwent total laparoscopic hysterectomy and bilateral salpingo-oophorectomy followed by bilateral retroperitoneal laparoscopic adrenalectomy two months later. The patient remains asymptomatic on maintenance hydrocortisone 18 months post diagnosis. This is the first report of solitary synchronous adrenal metastases in a patient with EC. Central MDT review is key in providing individualised treatment recommendations of such rare entity.
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PMID:An Unusual Presentation of Endometrial Cancer with Bilateral Adrenal Metastases at the Time of Presentation and an Updated Descriptive Literature Review. 3193 74

The incidence of endometrial cancer has rapidly risen over recent years. Paclitaxel, a key drug for endometrial cancer treatment, inhibits microtubule depolymerization and induces apoptosis in cancer cells. Endometrial serous carcinoma (ESC) accounts for < 10% of all endometrial carcinomas, but its aggressive nature makes it responsible for close to 40% of cancer deaths. Thus, novel therapeutic targets are required for ESC. To identify microRNAs that promote paclitaxel resistance, we established two paclitaxel-resistant cell lines from USPC1 human ESC cells by exposing paclitaxel to parental cells for 12 weeks. Paclitaxel concentrations were increased every 2 weeks, and after 12 weeks of paclitaxel exposure, two replicate paclitaxel-resistant cell lines were established (USPC1-PTSR1 and USPC1-PTXR2). The microarray analysis was performed using USPC1 cells and USPC1-PTXR1 cells, and eight candidate microRNAs were thus selected as potential mediators of paclitaxel sensitivity. Among these candidate microRNAs, let-7c precursor treatment of paclitaxel-resistant USPC1-PTXR1 cells caused the greatest increase in paclitaxel-mediated cytotoxicity. Let-7c inhibition conversely decreased paclitaxel-induced apoptosis. It is known that let-7a microRNA, a member of the let-7 family, inhibits growth of endometrial carcinoma cells targeting Aurora-B that controls progression through each phase of mitosis. We thus studied whether let-7c mediates Aurora-B expression in ESC cells. The expression levels of Aurora-B mRNA and protein were higher in USPC-PTXR1 cells compared with USPC1 cells. Let-7c inhibition increased Aurora-B expression in USPC1 cells but decreased Aurora-B expression in USPC1-PTXR1 cells. These results indicate that let-7c mediates paclitaxel resistance via inhibition of Aurora-B expression in ESC cells.
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PMID:MicroRNA Let-7c Contributes to Paclitaxel Resistance via Aurora-B in Endometrial Serous Carcinoma. 3272 72

Paclitaxel is one of the most effective and widely used agents in treating a variety of cancers, including endometrial cancer. Because of its poor solubility in water, the current intravenous pharmaceutical paclitaxel is formulated in Cremophor EL and dehydrated in ethanol in equal volumes. Cremophor EL is capable of causing complement activation, which can trigger an immediate hypersensitivity reaction. SPR064 is a pro-drug of paclitaxel which has a much higher solubility as compared to the parent drug; hence, SPR064 can be conveniently formulated in non-cremapor based medium, reducing the risk of cremaphor-related hypersensitivity reactions. The pharmacokinetics and solubility of SPR064 were evaluated in rats. The anti-tumorigenic potential of SPR064 was compared to paclitaxel in endometrial cancer cell lines and a genetically engineered mouse model (Lkbfl/flp53fl/fl ) of endometrial cancer. Overall, SPR064 exhibited improved solubility and better exposure to drug in rats when compared to paclitaxel. SPR064 and paclitaxel inhibited cell proliferation, induced apoptosis, enhanced cellular stress and caused cell cycle G1 arrest in endometrial cancer cell lines, with similar potency. Both SPR064 and paclitaxel reduced tumor weight in the Lkbfl/flp53fl/fl mouse model under obese and lean conditions compared to their respective controls. Immunohistochemical staining demonstrated that SPR064 and paclitaxel significantly reduced the expression of Ki-67 and BCL-xL in the endometrial tumors of both obese and lean mice. In summary, SPR064 has anti-tumorigenic effects that are equivalent to paclitaxel in endometrial cancer cell lines and a genetically engineered mouse model of endometrial cancer. Thus, SPR064 may be a promising therapy for endometrial cancer without the significant risk of hypersensitivity reactions seen with paclitaxel.
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PMID:SPR064, a pro-drug of paclitaxel, has anti-tumorigenic effects in endometrial cancer cell lines and mouse models. 3291 3


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