Angiotensin II (Ang II) induces, through AT1, intracellular Ca(2+) increase in both normal and cancerous breast cells in primary culture (Greco et al., 2002 Cell Calcium 2:1-10). We here show that Ang II stimulated, in a dose-dependent manner, the 24 h-proliferation of breast cancer cells in primary culture, induced translocation of protein kinase C (PKC)-alpha, -beta1/2, and delta (but not -epsilon, -eta, -theta, -zeta, and -iota), and phosphorylated extracellular-regulated kinases 1 and 2 (ERK1/2). The proliferative effects of Ang II were blocked by the AT1 antagonist, losartan. Also epidermal growth factor (EGF) had mitogenic effects on serum-starved breast cancer cells since induced cell proliferation after 24 h and phosphorylation of ERK1/2. The Ang II-induced proliferation of breast cancer cells was reduced by (a) Gö6976, an inhibitor of conventional PKC-alpha and -beta1, (b) AG1478, an inhibitor of the tyrosine kinase of the EGF receptor (EGFR), and (c) downregulation of 1,2-diacylglycerol-sensitive PKCs achieved by phorbol 12-myristate 13-acetate (PMA). A complete inhibition of the Ang II-induced cell proliferation was achieved using the inhibitor of the mitogen activated protein kinase kinase (MAPKK or MEK), PD098059, or using Gö6976 together with AG1478. These results indicate that in human primary cultured breast cancer cells AT1 regulates mitogenic signaling pathways by two simultaneous mechanisms, one involving conventional PKCs and the other EGFR transactivation.
Intraoperative application of TachoSil reduced rate of postoperative lymphocysts after PL, and it seems to provide a useful additional treatment option for reducing drainage volume and preventing lymphocele development after PL.
[Pt(O,O′-acac)(γ-acac)(DMS)] (PtAcD) is able to induce apoptosis in various human cancer cells, including the cisplatin-resistant human breast carcinoma MCF-7 cells. Here, to confirm that PtAcD has the potentiality for therapeutic intervention, we studied its effects in primary cultured epithelial breast cells obtained from cancers and also from the corresponding histologically proven non-malignant tissue adjacent to the tumor. We demonstrated that PtAcD (1) is more cytotoxic in cancer than in normal breast cells; (2) activated NAD(P)H oxidase, leading to PKC-ζ and PKC-α tanslocations; (3) activated antiapoptotic pathways based on the PKC-α, ERK1/2 and Akt kinases; (4) activated PKC-ζ and, only in cancer cell PKC-δ, responsible for the sustained phosphorylation of p38 and JNK1/2, kinases both of which are involved in the mitochondrial apoptotic process. Moreover, crosstalk between ERK/Akt and JNK/p38 pathways affected cell death and survival in PtAcD-treated breast cell. In conclusion, this study adds and extends data that highlight the pharmacological potential of PtAcD as an anti breast cancer drug.
Vinorelbine (i.v.) plus capecitabine (oral) combination therapy is active in anthracycline/taxane pretreated patients with metastatic breast cancer. Availability of oral vinorelbine provides this combination in an all-oral formulation. Two consecutive phase II trials differing only in vinorelbine administration routes evaluated their respective activities and tolerabilities in this population. In the i.v. group (n = 38) disease control was 61% (37% PR, 24% SD), median TTP 6.8 months and median survival 11.3 months. In the oral group (n = 38) disease control was 77% (5.4% CR, 34% PR, 38% SD), median TTP 7 months and median survival 10 months. G3-G4 neutropenia was more common in the oral group (p < 0.05); G2-G3 anaemia [5] and G3 thrombocytopenia [1] were observed only in the oral group. Although the comparison between the two regimens was not randomized, the results observed in these two consecutive phase II studies may suggest that oral and iv vinorelbine, in combination with capecitabine, can achieve similar responses in patients with metastatic breast cancer refractory to anthra-taxane combinations.
We evaluated the efficacy and safety of the use of a composite PTFE/polypropylene patch, Ventralex (Davol Inc., C.R. Bard, Inc., RI, USA), to repair, concurrent with laparoscopy, umbilical hernia in 51 postmenopausal women. After laparoscopy, patients were submitted to the hernia repair by a patch intraperitoneally placed behind the hernia. Primary outcomes included complication rates, while hernia recurrence was the secondary outcome. Patient age range was 58 ± 4.3 years, the size of patches was small in 17.6% of women, medium in 68.7% and large in 13.7%. Seventy-six percent of patients had an ASA I-II score, the mean operating time for hernia repair was 7 ± 2 minutes with 15 cc of related blood loss, with 1.8 days of hospital stay. The visual analogue scale was 0-3 for 62.7%, 4-6 for 27.5% and 7-10 for 9.8% of women. All laparoscopic and umbilical hernia repair terminated without any further intra or postoperative complications, with 36 months of follow-up; none of the patients showed recurrences. Combining laparoscopy and intraperitoneal mesh repair appears to be indicated for umbilical hernia treatment in post-menopausal patients undergoing laparoscopy, resulting in a safe and easy procedure, with short hospital stay and fast dismissal, with no major morbidity or recurrence.
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