Time and dose dependency of the suppression of pulmonary metastases of rat mammary cancer by amiloride.
Female; Animals; Rats; Drug Administration Schedule; Antineoplastic Agents/*administration & dosage; Neoplasm Transplantation; Amiloride/*administration & dosage; Lung Neoplasms/pathology/*prevention & control/*secondary; Plasminogen Activators/antagonists & inhibitors; Urokinase-Type Plasminogen Activator/antagonists & inhibitors; Dose-Response Relationship; Drug; Mammary Neoplasms; Experimental/*pathology; Inbred F344
Amiloride is an inhibitor of urokinase plasminogen activator (uPA), an essential component of the plasminogen/plasmin enzyme system. Inhibition of uPA prevents the conversion of plasminogen to tumor cell surface bound plasmin which is required for initiation of the metastatic process. MATB rat mammary cancer cells were introduced into the jugular venous system of 80 Fisher 344 female rats. Amiloride at high and low dosages was administered in the drinking water at the time of, prior to or several days following the tumor cell inoculation and continued daily for 10 days post inoculation. Control rats were maintained on water alone. The middle lobe of the right lung was examined microscopically for numbers of metastases. Suppression of metastases was significant at high amiloride dosages in all groups, and at low dosage when administered prior to inoculation. We conclude that amiloride suppresses induced metastases of rat mammary cancer, the effect being dose- and time-dependent.
Evans D M; Sloan-Stakleff K; Arvan M; Guyton D P
Clinical & experimental metastasis
1998
1998-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Facilitating breast-conserving surgery and preventing recurrence: aromatase inhibitors in the neoadjuvant and adjuvant settings.
Female; Humans; Neoadjuvant Therapy; Antineoplastic Agents/*administration & dosage; Aromatase Inhibitors/*administration & dosage; Breast Neoplasms/*drug therapy/*surgery; Neoplasm Recurrence; Segmental; *Mastectomy; Adjuvant; Chemotherapy; Local/*prevention & control
Breast-conserving surgery (BCS) is an attractive option for many patients with early-stage breast cancer, because it provides a better cosmetic outcome than modified radical mastectomy, while reducing surgical morbidity. In patients with large, operable breast tumors who are ineligible for BCS, neoadjuvant therapy is a useful option for reducing the tumor size and for increasing the proportion of candidates for BCS. In patients with endocrine-responsive tumors, neoadjuvant endocrine therapy with either tamoxifen or an aromatase inhibitor (AI; anastrozole, letrozole, or exemestane) provides an alternative to neoadjuvant chemotherapy. Clinical trials have demonstrated the superiority of neoadjuvant AIs over tamoxifen in achieving a clinical response and increasing the frequency of BCS. In addition, adjuvant endocrine therapy with AIs, whether used as initial therapy instead of tamoxifen, in a switching strategy after 2-3 years of tamoxifen, or as extended adjuvant therapy after 5 years of adjuvant tamoxifen, has been shown in several randomized clinical trials to improve disease-free survival, reduce distant metastases and, in some cases, improve overall survival. The availability of the AIs for effective and well-tolerated neoadjuvant and/or adjuvant endocrine therapy represents an important advance in breast cancer treatment, and surgeons should be familiar with these new therapeutic options.
Mamounas Eleftherios P
Annals of surgical oncology
2008
2008-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1245/s10434-007-9702-3" target="_blank" rel="noreferrer noopener">10.1245/s10434-007-9702-3</a>