Mifepristone demonstrates activity in both HEC-1-A and Ishikawa cells at clinically relevant concentrations based on an oral human dose of about 200 mg/day. While its mechanism of action remains unknown, this data supports an increase in apoptosis that may be due to p53 activation rather than hormone receptor mediation. Additional studies are needed to help further identify mifepristone mechanism of action.
These data suggest that EGFRinhibitors, such as gefitinib, have the potential to modulate common mechanisms of drug resistance and may have a role in optimizing antineoplastic regimens for the treatment of recurrent endometrial cancer. This may represent a promising option for this class of agents in the treatment of endometrial cancer.
This data suggests that EGFR-inhibitors, such as gefitinib, have the potential to modulate common mechanisms of drug resistance and may have a role in optimizing chemotherapy regimens for the treatment of ovarian cancer.
Objective. The primary objective of this study was to evaluate the potential to increase the in vivo activity of liposomal doxorubicin when administered in combination with other chemotherapeutic agents such as topotecan, docetaxel, gemcitabine, capecitabine, or celecoxib in an ovarian cancer xenograft mouse model to identify new treatment options for recurrent platinum-sensitive/resistant ovarian cancer. Methods. This was a five-arm study in two xenograft ovarian cancer mouse models, ES-2 (platinum-sensitive), and OVCAR3 (platinumresistant), to evaluate the combination of liposomal doxorubicin with the common chemotherapeutic agents. Each cell line had five mice for each treatment arm, five vehicle control mice, and five liposomal doxorubicin alone control mice. Experiments were done in duplicate. Results. The percentage tumor reduction ranged from 52% to 74.1% for the single-agent treatment arms. Tumor growth inhibition and regression (response) was improved on the combination treatment arms ranging from 76.1% to 100%.We observed increased activity in the liposomal doxorubicin plus topotecan arm, with a 27.3% improvement in response, compared with either agent alone. Conclusions. The addition of liposomal doxorubicin demonstrated increased antitumor activity compared with either agent used alone. The most active combination treatment arm was liposomal doxorubicin with topotecan which is consistent with recent clinical study reports of enhanced activity with the combination of topoisomerase I and topoisomerase II agents. Additional studies are warranted to evaluate the efficacy and safety to optimize the combination of liposomal doxorubicin and topotecan for the treatment of recurrent or refractory ovarian cancer.
At clinically achievable concentrations only B(0)C significantly inhibited COMT activity and increased CE concentrations. Short-term exposure did not alter the rate of cancer cell growth. Confirmation is needed to determine the clinical impact of long-term exposure to and the use of echinocandins with catechol functional groups.
Purpose: Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals extracted from the culture of the basidiomycete mushroom Lentinula edodes (shiitake) that has been proposed to have many health benefits including both immunomodulatory and anti-tumor effects. In clinical studies AHCC has demonstrated numerous immunomodulating and potential restorative effects on natural killer (NK) cells, macrophages and cytokines. The objectives of this study were to evaluate if daily treatment with AHCC would eradicate human papillomavirus (HPV) 16/18 expression and prevent or delay cervical tumor growth using human xenograft mouse model.
Methods: Selected cervical cancer cells, SiHa (HPV 16/18 positive), and C-33A (HPV negative) were treated in vitro with a single dose AHCC 0.42 mg/mL and incubated for 72 hours. In the second study AHCC dose was repeated once every 24 hours for total of seven days. This was followed by a three arm in vivo study in two xenograft cervical cancer mouse models, SiHa (HPV 16/18 positive), and C-33A (HPV negative), in which each cell line had ten mice for the treatment arm, vehicle control arm and no treatment arm. Mice in the treatment arm received 50 mg/kg AHCC in 0.25 mL of sterile water every day for seven days before the injection of the tumor cells and until the completion of the study. Tumors were measured three times per week. After 90 days of treatment, there was a 30 day observation period to evaluate the potential for recurrence of the HPV infection and the impact on tumor growth. At the end of the study, tumors were extracted and RT-PCR was completed on DNA samples from extracted protein to evaluate the HPV expression.
Results: In vitro treatment with a single dose of AHCC for 72 hour incubation suppressed HPV expression in the first 24 hours but then HPV expression recovered by 48 hours. However, with continuous in vitro exposure, sustained HPV suppression was observed. In the in vivo animal studies, expression of HPV was eradicated with once daily AHCC dosing for 90 days and no detection of HPV expression was sustained after 30 days off treatment. In addition, AHCC daily treatment was associated with a 15.9% decrease in SiHa (HPV 16/18 positive) tumor growth compared to the untreated control (P< 0.05). AHCC did impact the growth rate of the C-33A (HPV negative) tumors.
Conclusion: In conclusion, these data suggest daily dosing of AHCC will eradicate HPV 16/18 infections and may have a role in the prevention of HPV-related cervical cancer. Furthermore, there is a potential for the addition of AHCC to primary treatment regimens for cervical cancer, which may potentially improve response rates and prevent recurrence. A confirmatory pilot study in HPV positive women is underway.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B79.
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