In vitro growth regulation of endometrial carcinoma cells by tamoxifen and medroxyprogesterone acetate,

The growth inhibitory effects of medroxyprogesterone acetate (MPA) and tamoxifen (TAM) were tested on three long-established endometrial carcinoma cell lines (HEC-1, KLE, and RL95-2) and on UM-EC-1, a new endometrial carcinoma cell line established in our laboratory. MPA and TAM were used in growth experiments either alone, simultaneously, or sequentially. The MCF-7 breast cancer cell line was used as a control. None of the endometrial carcinoma cell lines showed significant sensitivity to 0.1-10 [mu]M MPA. In contrast, 10 days exposure to 5 [mu]M TAM induced 83 and 70% growth inhibition in HEC-1 and KLE cultures, whereas the growth of UM-EC-1 was inhibited by 99.7% and RL95-2 cultures by 100%. TAM-induced growth inhibition was reversible since all cell lines resumed logarithmic growth when TAM was removed from the culture medium. Addition of 17-[beta]-estradiol (E2) to the culture medium did not accelerate recovery, and reversal of TAM-induced growth inhibition was not seen when TAM and E2 were added simultaneously. This is consistent with our finding that, except for MCF-7, these cell lines did not show detectable estrogen receptor (ER) activity in assays performed at the time of these experiments. When treated sequentially with TAM and MPA, all cell lines resumed logarithmic growth when medium containing TAM was replaced with medium containing MPA. Simultaneous exposure to 5 [mu]M MPA and 5 [mu]M TAM resulted in a slight additive growth inhibitory effects only in KLE cultures. Our results show that MPA does not have growth inhibitory effects in these endometrial carcinoma cell cultures, whereas TAM exerts a potent growth inhibitory effect that is not reversed by estrogen and may thus be mediated through a mechanism different from blockade of ER. In vitro results with the UM-EC-1 cell line correlated with the clinical response of the cell line donor. Her disease progressed during postoperative MPA therapy, but subsequently she responded to TAM therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27275/1/0000291.pd

Evaluation Criteria for Digital Rights Management Schemes with Focus on Music E-business

Abstract: The networked environment we live in is changing our consumption habits. Peer-to-peer distribution networks, enabled by high-speed home connections to the Internet, have raised fear in both the music and the movie industry. In the past few years, however, this attitude has changed. Instead of condemning peer-to-peer applications, the industry has made an honest effort to turn them into profit. Securing revenue will, however, require some form of technical protection. This is where Digital Rights Management (DRM) steps into the picture. In this paper we developed a set of common criteria that can be used to evaluate both open and proprietary DRM schemes that are intended for protecting digital music. Our criteria take into account issues that are important for both the content provider as well as the end-user. We evaluated four DRM schemes against the criteria: Apple's Fairplay, RealNetworks ' Helix DRM, Microsoft's Windows Media DRM and OMA DRM 2.0. None of the evaluated schemes fulfil the evaluation criteria completely- yet the criteria do identify the strengths and weaknesses of each scheme well. We conclude that the end-user is likely to benefit from an open and standardised scheme as it will not create vendor or device lock-in. A standardised scheme can also likely be secure because of extensive technical review during the standardisation process. However, the thorough standardisation process might take too long time for the content providers. By making a proprietary scheme, the content provider can cut the time to market in hope of quickly claiming new and emerging market shares. Market shares can also be secured by making rich and attractively priced content available through online shops that are easy to use. Keywords: Digital Rights Management, Music, E-business 1

Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer - Results from two randomised studies

INTRODUCTION: Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled. METHODS: Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy. RESULTS: In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01). CONCLUSION: Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results

P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines Presented at the American Association of Cancer Research 91st Annual Meeting, San Francisco, California, April 1–5, 2000.

Background. A critical factor for successful organ preservation treatment in head and neck cancer may be selecting tumors that respond to chemotherapy and radiation. Previous results in patients indicated that tumors that overexpressed p53 were more sensitive to chemotherapy than those that did not overexpress p53. Methods. To determine the relationship of p53 mutations to sensitivity to cisplatin in vitro, 23 head and neck squamous cell carcinoma (HNSCC) cell lines were analyzed for cisplatin sensitivity, p53 expression, and p53 mutation status. Results. Mutations of the p53 gene were identified in 13 of 23 of the cell lines tested. Mutation of the p53 gene was significantly associated with high levels of expression of the p53 protein. The average ID 50 (drug dose required to inhibit 50% of cell growth) for cell lines with mutant p53 was 6.8 ΜM, whereas the average ID 50 for cell lines with wild-type p53 was 13.7 ΜM. Conclusions. These in vitro data support a role for mutation of the p53 tumor suppressor gene as a marker for response to cisplatin in HNSCC. © 2003 Wiley Periodicals, Inc. Head Neck 25: 654–661, 2003Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35126/1/10274_ftp.pd

Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: A phase III, randomised, multicentre trial (Ovaresist)

Background: Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC. Methods: Patients with PROC were randomised (2 : 1) to chemotherapy (weekly paclitaxel 80 mg m−2 or four weekly pegylated liposomal doxorubicin 40 mg m−2) or tamoxifen 40 mg daily. The primary end point was HRQoL. Secondary end points were PFS by RECIST and overall survival (OS). Results: Between March 2002 and December 2007, 156 and 82 patients were randomised to chemotherapy and tamoxifen, respectively. In the chemotherapy arm, a significantly larger proportion of patients experienced a worsening in their social functioning. There was no difference in the proportion of patients experiencing improvement of gastrointestinal symptoms. Median PFS on tamoxifen was 8.3 weeks (95% CI, 8.0–10.4) compared with 12.7 weeks (95% CI, 9.0–16.3) on chemotherapy (HR, 1.54; 95% CI, 1.16–2.05; log-rank P=0.003). There was no difference in OS between the treatment arms. Conclusions: Patients on chemotherapy had longer PFS but experienced more toxicity and poorer HRQoL compared with tamoxifen. Control over gastrointestinal symptoms was not better on chemotherapy. These data are important for patient counselling and highlight the need to incorporate HRQoL end points in studies of PROC