Prognostic value of HER3, PTEN and p-HER2 expression in patients with HER2positive breast cancer.

BACKGROUND: HER2 overexpression is an unfavorable prognostic factor in patients with breast cancer, but it is also a target for the monoclonal antibody trastuzumab, which is effective in adjuvant and palliative settings. HER2 positivity is an inclusion criterion for immunotherapy, but it is not a positive predictive factor, and only half of patients benefit from the treatment. AIM: The aim of this study was to evaluate the prognostic and predictive value of HER3, PTEN and phosphorylated HER2 (p-HER2) expression in primary breast tumors of patients treated with trastuzumab in an adjuvant or palliative regimen. MATERIAL/METHODS: Immunohistochemical (IHC) analysis with 3 antibodies specific to the proteins was performed in tumor specimens obtained from 81 HER2-positive patients treated with trastuzumab. RESULTS: HER3 overexpression was present in 55.6% of the examined tumors, and PTEN or pHER2 positivity was present in 32.0% and 34.6% of them, respectively. HER3 overexpression and PTEN positivity correlated with larger tumor size (p=0.016 and p=0.008, respectively). p-HER2 positivity correlated with more advanced clinical stage of the disease (p=0.032). There was no correlation between the proteins' expression and survival for 31 patients treated with trastuzumab in the palliative regimen. DISCUSSION: HER3 overexpression, PTEN positivity and p-HER2 positivity in tumor cells of HER2-positive patients correlate with more advanced clinical stage of breast cancer. Expression of these proteins does not predict outcome of trastuzumab treatment.

The changes of blood platelet activation in breast cancer patients before surgery, after surgery, and in various phases of the chemotherapy.

Blood platelets from patients with cancer (before or after the surgery) exhibit a variety of qualitative abnormalities. Different anti-cancer drugs may also induce the oxidative/nitrative stress in blood platelets and change their hemostatic properties. The aim of our study was to explain the effect of superoxide anion radicals ([Formula: see text]) production on hemostatic properties of blood platelets (activated by a strong physiological agonist - thrombin) from breast cancer patients before the surgery, after the surgery, and after various phases (I-IV) of chemotherapy (doxorubicin and cyclophosphamide). Patients were hospitalized in the Department of Oncological Surgery and at the Department of Chemotherapy, Medical University of Lodz, Poland. We measured the platelet aggregation as the marker of hemostatic activity of blood platelets. We observed an increase of [Formula: see text] in thrombin-activated blood platelets from patients with breast cancer (before or after the surgery and after various phases of the chemotherapy) compared to the healthy group. Our other experiments demonstrated that aggregation (induced by thrombin) of blood platelets from patients with breast cancer before the surgery, after the surgery, and after various phases of the chemotherapy differs from aggregation of platelets obtained from healthy volunteers. Moreover, our results showed the correlation between the [Formula: see text] generation and changes of platelet aggregation in breast cancer patients before the surgery, after the surgery, and after the chemotherapy (I and IV phases). Considering the data presented in this study, we suggest that the production of [Formula: see text] in blood platelets (activated by thrombin) obtained from breast cancer patients may induce the changes of platelet aggregation, which may contribute in thrombosis in these patients.

Changes in plasma thiol levels induced by different phases of treatment in breast cancer; the role of commercial extract from black chokeberry.

Different low-molecular-weight thiols, including glutathione, cysteine, and cysteinylglycine are physiological free radical scavengers. On the other hand, homocysteine may play a role as an oxidant. The aim of our present study was to establish in vitro the effects of the commercial extract of Aronia melanocarpa (Aronox(®)) on the amount of selected low-molecular-weight thiols and the activity of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in plasma obtained from patients with invasive breast cancer during different phases of treatment [before or after the surgery and patients after different phases of chemotherapy (doxorubicin and cyclophosphamide)] and from healthy subjects. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy, Medical University of Lodz, Poland. The level of low-molecular-weight thiols was determined by high-performance liquid chromatography. We observed that in the presence of the Aronia extract changes in amount of thiols in plasma from breast cancer patients (at all tested groups) were significantly reduced. Our results showed that tested commercial extract reduced modifications of antioxidative enzymes activity in plasma from patients during different phases of treatment, but this effect was not statistical significant. Our results suggest that the Aronia extract supplementation in breast cancer patients has a beneficial effect on thiols concentration in plasma. Plasma, as reported in this work, could be used as an experimental model to evaluate the beneficial action of plant supplements, including phenolic extracts on thiols or other molecules during different phases of treatment.

Effects of the commercial extract of aronia on oxidative stress in blood platelets isolated from breast cancer patients after the surgery and various phases of the chemotherapy.

Since the extract from berries of Aronia melanocarpa presents antioxidative properties in plasma and in blood platelets, not only from healthy group, but also from patients with benign breast diseases and in patients with invasive breast cancer before surgery, the aim of our present study was to evaluate the oxidative stress by measuring the level of various biomarkers of this process such as the generation of superoxide anion radicals (O(2)(-·)), the amount of carbonyl groups and 3-nitrotyrosine in proteins or the amount of glutathione in blood platelets isolated from breast cancer patients after the surgery and after various phases of the chemotherapy in the presence of A. melanocarpa extract (Aronox) in vitro. We demonstrated in platelet proteins from patients with invasive breast cancer (after the surgery and after various phases of the chemotherapy) higher level of carbonyl groups than in control healthy group. The level of 3-nitrotyrosine in platelet proteins from patients with invasive breast cancer was also significantly higher than in healthy subject group. We observed an increase of other biomarkers of oxidative stress such as O(2)(-·) and a decrease of GSH in platelets from patients with breast cancer (after the surgery and after various phases of the chemotherapy) compared to the healthy group. In model system in vitro our results showed that the commercial extract from berries of A. melanocarpa due to antioxidant action, significantly reduced the oxidative/nitrative stress in platelets from patients with invasive breast cancer caused by the surgery and various phases of the chemotherapy.

[Transmembrane transporters ABCC - structure, function and role in multidrug resistance of cancer cells]. / Transportery blonowe ABCC ­ budowa, funkcja i znaczenie w mechanizmach wytwarzania opornosci wielolekowej w komórkach nowotworów zlosliwych.

Resistance to cytotoxic drugs is a significant problem of systemic treatment of cancers. Apart from drug inactivation, changes in target enzymes and proteins, increased DNA repair and suppression of apoptosis, an important mechanism of resistance is an active drug efflux from cancer cells. Drug efflux across the cell membrane is caused by transport proteins such as ABC proteins (ATP-binding cassette). This review focuses on the ABCC protein subfamily, whose members are responsible for multidrug cross-resistance of cancer cells to cytotoxic agents. The authors discuss the structure of ABCC proteins, their physiological function and diseases provoked by mutations of respective genes, their expression in many different malignancies and its connection with resistance to anticancer drugs, as well as methods of reversion of such resistance.