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

Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%). Three patients with bone metastases from breast cancer developed hypercalcemia. At doses greater than or equal to 40 mg/day a decline in LH and FSH occurred which was not statistically significant. At all doses tested SHBG rose during therapy. A dose dependent estrogenic blockade was seen on the vaginal epithelium following challenge with transdermal estradiol. Steady-state concentrations of toremifene were reached within 4 weeks, and at doses greater than or equal to 60 mg/day ranged from 879-3445 ng/ml. The half-life was found to be 5 days, and at three weeks following discontinuation of treatment concentrations greater than 24 ng/ml were detected. The N-desmethyl and 4-hydroxy metabolites achieved steady state levels within 4 weeks and had half-lives of 6 and 5 days respectively. Partial responses were seen in 4 patients, 3 with breast cancer treated at 200 mg/day and 1 with endometrial cancer treated at 400 mg/day.
 ...
PMID:Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. 214 80

From 1960 to 1977, eighty-three patients with stage IV endometrial carcinoma were treated in the Norwegian Radium Hospital. The lung was the main site of extrapelvic tumor extension (36%), followed by "multiple sites" (23%), lymph nodes (inguinal, supraclavicular, axillar; 13%), and bladder (13%). The actuarial 5-year-survival rate was 10%. Complete clinical remission was achieved in 5 patients with lung metastases, in 2 with inguinal lymph node metastases, and in 1 patient with ascites with positive cytology. Control of pelvic disease could be achieved in 20 of 72 patients (28%) by radiotherapy alone or combined with surgery and/or progestagens. Progestational agents proved to be of benefit especially for patients with lung metastases. A complete remission of all visible lesions was observed in 8 out of 26 patients (31%). Patients with well- and moderately differentiated primary adenocarcinoma had a response rate of 83% as opposed to 14% for patients with poorly differentiated adenocarcinomas and adenosquamos carcinomas. Extrapelvic tumor localizations, suitable for radiotherapy, were supraclavicular and axillary lymph nodes and bone metastases.
 ...
PMID:Stage IV endometrial carcinoma: a clinical and histopathological study of 83 patients. 669 54

Metastasis to the peripheral skeleton, especially in the face of low stage disease, is rare. This report describes the case of a 77-year-old lady with stage IC disease who underwent curative total abdominal hysterectomy and bilateral salpingo-oopherectomy 2 years prior to presenting with a painless gigantism of her fourth toe. A histologic diagnosis of dedifferentiated endometrial metastasis with sarcomatous differentiation was made following amputation of the toe. Osseous metastasis to bone is discussed in the context of endometrial carcinoma and the literature reviewed. This paper reports the first case of endometrial carcinoma metastasis presenting as gross swelling of a toe.
 ...
PMID:Endometrial cancer metastasis presenting as a grossly swollen toe. 1467 34

Most rhabdomyosarcomas of the vagina (RMSV) occur in infants and children up to six years old. RMSV in elderly patients is extremely rare. We report a case of a 70-year-old woman with RMSV. She had received surgery for uterine endometrial cancer one year before and a vaginal polypoid tumor was noted during routine follow-up vaginal examination. She was referred to our department for radiation therapy following partial tumorectomy of the lesion. She was given three sessions of intra-vaginal radiation therapy, once a week with 6 Gy at 7.5 mm below the vaginal surface and external irradiation of 50 Gy to the pelvis. However, paraaortal lymph node metastasis developed during initial radiation therapy. Furthermore, multiple bone metastases appeared at the completion of the radiation therapy. Six months after initial treatment the patient died from progression of the disease. Autopsy demonstrated small residual tumor at the primary site as well as multiple systemic metastases.
 ...
PMID:A case of rhabdomyosarcoma of the vagina in an elderly woman. 1528 17

The available monolayer culture systems for the study of bone metastases constitute a suboptimal simulation of the in vivo pathophysiology of bone metastases, and therefore, do not provide sufficient information to assess the morphologic evidence of bone reaction to cancer cells, the nature of cell-specific mediators of osteolysis and osteoplasia and the response to treatment. Therefore, we have developed a three-dimensional (3-D) type I collagen gel system that allows co-culture of human osteoblasts (MG-63) with cancer cells, such as MCF-7, MDA-MB-231 or ZR-75 breast cancer cells, PC-3 prostate cancer, KLE endometrial cancer cells and Calu-1 lung cancer cells. We used type I collagen purified from rat tail tendons and the 3-D system was prepared by mixing MG-63 cells with type I collagen in 24-well plates. The 3-D system was inoculated with cancer cells and processed with standard cell culture procedures. After 1 week of culture, the matrix gel was fixed with formalin and embedded in paraffin. Serial sections were stained with trichrome Masson stain and modified Masson-Goldner stain, as well as analyzed by in situ hybridization, immunohistochemistry and the TUNEL technique for semi-quantitative detection of apoptotic cell death, assessing the response to adriamycin therapy. The inoculation of PC-3 cells in this collagen matrix produced a blastic reaction, documented by an increased number of MG-63 cells and increased density of type I collagen. The human KLE cells and inoculation of cell-free media produced no reaction, while ZR-75, MCF-7 and Calu-1 cells produced local degradation of the collagen matrix. In situ hybridization revealed the expression of Insulin-like growth factor 1 (IGF-1) and urokinase-type plasminogen activator (uPA) mRNA, while immunohistochemistry detected differential expression of uPA and cathepsin D. Adriamycin induced apoptotic cell death in prostate cancer cells and estrogen receptor negative (ER-) MDA-MB-231 breast cancer cells, while adriamycin did not induce apoptosis but cytostasis in ER+ MCF-7 cells. The adriamycin-induced apoptosis was inhibited by co-culture with osteoblast-like cells (MG-63). We conclude that this 3-D culture system is a useful in vitro model allowing the analysis of local mediators of osteolytic and osteoblastic reactions to bone metastases and treatment response.
 ...
PMID:Three-dimensional type I collagen co-culture systems for the study of cell-cell interactions and treatment response in bone metastases. 1575 11

Endometrial carcinoma is the most common invasive cancer of the female genital tract and accounts for 7% of all invasive cancer in women. Bony metastasis is uncommon with endometrial carcinoma and distal metastasis is very rare. The purpose of this paper is to present a case of an 86 year-old female with endometrial carcinoma metastasis to the distal phalanx of the hallux. The patient had a known history of endometrial carcinoma with metastases (FIGO IIIC), and had been diagnosed with pulmonary and bony metastases 2 months prior to presentation. Her initial foot complaint was of a painful, infected ingrown toenail. The infection continued to progress following avulsion of the nail, and the patient was then diagnosed with osteomyelitis. Given her past history, the possibility of metastasis to the hallux was also considered. A hallux amputation was performed, and the pathology report revealed the diagnosis of endometrial carcinoma metastasis to the distal phalanx of the hallux. While the amputation site healed uneventfully, the patient refused further treatment measures for her carcinoma and eventually succumbed to the disease.
 ...
PMID:Endometrial carcinoma metastasis to the distal phalanx of the hallux: a case report. 1625 76

The endothelin axis (ET axis), comprising the three peptides endothelin (ET)-1, -2, -3 and their receptors ET(A)R and ET(B)R, is expressed in various cells and tissues. The biologically active ET-1 is formed by endothelin-converting enzyme (ECE) from inactive big-ET-1. ET-1 has emerged as an important peptide in a host of biological functions, including development, cellular proliferation, apoptosis and angiogenesis, thereby playing an important physiological and pathophysiological role. As these effects are mediated by ET(A)R, activation of ET(B)R prevents apoptosis, inhibits ECE expression and mediates the clearance of ET-1. Emerging data indicate that the ET axis is involved in tumourigenesis and tumour progression of various cancers. Expression of the ET axis has been demonstrated in a wide range of human tumours. Since most data have been reported for female malignancies, this review will focus on the role of the ET axis in cancers of the ovary, the cervix and the breast. In ovarian cancer, activation of ET(A)R by ET-1 is a key mechanism in the cellular signalling network promoting cancer growth and progression. Similar effects have been shown for cervical and endometrial cancer. In breast cancer, ET-1 via ET(A)R promotes proliferation and invasion, mediates bone metastases and predicts unfavourable response to chemotherapy. The outstanding role of ET-1 and ET(A)R in carcinogenesis and tumour progression has led to an extensive search for interfering agents, resulting in the development of selective ET(A)R antagonists on the one hand and inhibitors of the endothelin-converting enzyme (ECE) on the other. Targeting the ET axis via ET(A)R or ECE blockade seems to be a promising approach in the treatment of female malignancies.
 ...
PMID:The endothelin axis: a novel target for pharmacotherapy of female malignancies. 1762 67

We report an unusual case of solitary osteolytic tibial metastasis from a primary endometrial cancer in a 62-year-old woman. The primary cancer was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy combined with postoperative external beam radiotherapy, while the tibial metastasis was treated with an above knee amputation. The rarity of the case lies on the fact that metastases distally to the elbow and knee are uncommon and endometrial cancer rarely gives distal bone metastases and particularly solitary to the extremities.
 ...
PMID:Solitary tibial osteolytic lesion. 1971 52

Hematogenous bone metastases from endometrial carcinoma are not frequent and their treatment is a matter of debate. We describe an extremely rare case of calvarial metastasis from endometrial carcinoma in an 80-year-old woman treated by means of one-step surgical radical resection and heterologous cranioplasty, along with a review of the literature regarding epidemiology, clinico-radiological features, prognosis, and management of skull metastases.
...
PMID:Calvarial metastasis from endometrial carcinoma: Case report and review of the literature. 2568 34

Being a tumor suppressor, PTEN functions as a dual-specificity protein and phospholipid phosphatase and regulates a variety of cellular processes and signal transduction pathways. Loss of PTEN function has been detected frequently in different forms of cancers, such as breast, prostate and lung cancer, gastric and colon cancer, skin cancer, as well as endometrial carcinoma. In this review, we provide a summary of PTEN and its role in bone malignancies including bone metastases, multiple myeloma, and osteosarcoma, etc. We highlight the importance of PTEN loss leading to activation of the oncogenic PI3K/Akt/mTOR pathway in tumorigenesis and progression, which can be attributed to both genetic and non-genetic alterations involving gene mutation, loss of heterozygosity, promoter hypermethylation, and microRNA mediated negative regulation. We also discuss the emerging therapeutic applications targeting PTEN loss for the treatment of these bone malignant diseases.
 ...
PMID:Oncogenic and Therapeutic Targeting of PTEN Loss in Bone Malignancies. 2577 92


1 2 Next >>