Urszula Czernek

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.

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.

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 () 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 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 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 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.

Chemotherapy modulates the biological activity of breast cancer patients plasma: The protective properties of black chokeberry extract

In breast cancer patients (before and during anti-cancer therapy) oxidative/nitrative damage to various molecules is observed. Furthermore, anti-cancer treatments may also influence the hemostatic properties of blood platelets and plasma. The aim of our study was to assess the effect of oxidative/nitrative stress (estimated by measurements of the levels of carbonyl groups and 3-nitrotyrosine in proteins--ELISA and C-ELISA methods, respectively; lipid peroxidation and total antioxidant level--TAS) on the selected parameters of hemostatic activity of plasma (the process of fibrin polymerization and lysis) collected from breast cancer patients after surgery and after various phases of chemotherapy (doxorubicin and cyclophosphamide). Subsequently, we also evaluated the level of oxidative/nitrative stress and hemostatic activity in plasma from these patients in the presence of the commercial extract of Aronia melanocarpa (Aronox®) in vitro. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy in Medical University of Lodz, Poland. We observed increased levels of biomarkers of oxidative/nitrative stress in plasma from patients with breast cancer (before or after surgery and after various phases of chemotherapy) in comparison to healthy group. Our further experiments demonstrated the hemostatic activity of plasma from the investigated patients differs from hemostatic properties of plasma obtained from healthy volunteers. We also recognize the existence of a relationship between oxidative stress (measured by the level of carbonyl groups) and changes of hemostasis in breast cancer patients after I and IV phases of chemotherapy. Moreover, the obtained results showed that the commercial extract from A. melanocarpa berries significantly reduced, in in vitro system, the oxidative/nitrative stress and hemostasis changes in plasma from breast cancer patients, after surgery and different phases of chemotherapy. Considering the data presented in this study, we suggest that the oxidative/nitrative stress in plasma obtained from breast cancer patients (not only before or after the surgery, but also after various phases of doxorubicin and cyclophosphamide chemotherapy) may induce changes of hemostatic activity, which may contribute to thrombosis in these patients. Our results also suggest that the commercial extract of A. melanocarpa may be regarded as a promising new source of bioactive antioxidant natural compounds for breast cancer patients.

Synchronous primary ovarian and endometrial cancers: a series of cases and a review of literature.

Synchronous cancers account for 0.7-1.8% of all gynecologic cancers. Among them, synchronous ovarian and endometrial cancers are predominant (40-53%). Patients with synchronous cancers have better prognosis than those with single disseminated cancer. We present 10 patients with synchronous ovarian and endometrial cancers who were treated at the Chemotherapy Department of the Medical University of Lodz in 2009-2013. The most often reported symptom of the disease was abnormal vaginal bleeding (6 patients). The range of the patients’ age was 48-62 and the median age was 56. Five patients had stage I of ovarian cancer, single patients had stage IIA, IIB and IIIB, 2 patients had stage IIIC. Three patients had I, 5 – II, and 2 – III stage of endometrial cancer. All patients had endometrioid type of endometrial cancer, 7 of them had also the same histological type of ovarian cancer. All patients had adjuvant chemotherapy because of ovarian cancer, none of them had adjuvant radiotherapy. One patient was lost to follow up. For other patients a median follow up was 13 months (range: 3-53 months). One patient experienced relapse, all patients are alive. Synchronous ovarian and endometrial cancers are usually diagnosed at an earlier stage, have lower histological grade and better prognosis than single cancers. The most common histological type of both endometrial and ovarian cancers is endometrioid carcinoma. The first symptoms reported by our patients and the course of the disease were concordant with data from the literature.

Secondary cancer in a survivor of Hodgkin's lymphoma: A case report and review of the literature

Hodgkin’s lymphoma (HL) is one of the most curable malignant diseases in adults. However, HL patients have a higher risk of developing second malignancies compared with the general population. The population of adult cancer survivors is growing, thus, the long-term effects of cancer treatment, including secondary cancer development, have become an increasingly important concern in the field of oncology. The current study presents the case of a female HL survivor who developed two secondary malignancies within 29 years of follow-up. Furthermore, a review of the literature was conducted, which focused on secondary breast and gastrointestinal cancers in HL survivors.

The role of preoperative systemic treatment in patients with breast cancer

The goal of preoperative pharmacotherapy in patients with breast cancer is to enable breast conserving surgery in stage T3N0-1M0 or radical mastectomy in patients with primary inoperative tumors (T1-4N0-3M0). The choice of optimal treatment should be based not only on risk factors resulting from the stage but also on predicted cancer responsiveness to the treatment. The breast cancer subtypes defined by immunohistochemical profile (expression of ER, PR, HER2 and Ki67) are characterized by different responsiveness to therapy. Complete response confirmed by histopathological evaluation after neoadjuvant chemotherapy is a positive prognostic factor in some breast cancer subtypes. This marker is not of value in postmenopausal patients with ER/PR+ HER2– tumors, who are candidates for neoadjuvant hormone therapy. These patients have a good prognosis if in a histopathological report after surgery there are features such as pT1, pN0, Ki67 < 3%, and ER Allred score ≥ 3. The goal of the paper is to present current knowledge about preoperative pharmacotherapy of breast cancer.

Paraneoplastic Cushing’s syndrome in a patient with small cell lung cancer: case report

We discuss the case of small-cell lung cancer patient with clinical features of paraneoplastic Cushing’s syndrome. The primary symptoms included electrolyte imbalance, glucose intolerance, and increased oedemas of the lower extremities. In January 2016, the patients performance status was 2 in ECOG scale and antineoplastic treatment with carboplatin and etoposide was initiated. Following the 2nd chemotherapy cycle symptoms of paraneoplastic syndrome significantly were alleviated and performance status improved (grade 1), allowing a change of chemotherapy protocol to a more standard one (cisplatin and etoposide). At the time of the subsequent chemotherapy cycles the patents good general condition was maintained. Use of causative treatment allowed achievement of significant clinical improvement and recovery of laboratory values.

Review of preoperative hormonal therapy in patients with breast cancer

Przedoperacyjne leczenie systemowe u chorych na raka piersi jest stosowane w celu umozliwienia operacji oszczedzającej narząd (T3N0-1M0) lub wykonania radykalnego zabiegu u chorych z pierwotnie nieoperacyjnym guzem (T1-4N0-3M0). Przed rozpoczeciem leczenia nalezy przeprowadzic badania diagnostyczne mające na celu dokladne rozpoznanie histopatologiczne z oceną ekspresji receptorow hormonalnych HER2 i Ki67 oraz ustalenie zaawansowania miejscowego choroby i wykluczenie obecności przerzutow odleglych. Jezeli planowany jest zabieg oszczedzający narząd, miejsce guza nalezy zaznaczyc tatuazem lub metalowym klipsem. Zgodnie z rekomendacjami Europejskiego Towarzystwa Onkologii Klinicznej (European Society of Medical Oncology — ESMO) wybor farmakoterapii przedoperacyjnej powinien byc uzalezniony od przewidywanej wrazliwości na leki oraz — w mniejszym stopniu — od ryzyka związanego z duzym zaawansowaniem choroby. Osiągniecie calkowitej remisji potwierdzonej badaniem mikroskopowym po wstepnej chemioterapii wiąze sie z lepszym rokowaniem. U chorych na raka o podtypie luminalnym A (tzn. z ekspresją receptorow hormonalnych, brakiem cechy HER2 i ekspresją Ki67 mniejszą niz 14%) oraz na raka zrazikowego z obecnością receptorow hormonalnych taka odpowiedź na chemioterapie wystepuje bardzo rzadko. U takich chorych, szczegolnie po menopauzie, nalezy rozwazyc wlączenie hormonoterapii przedoperacyjnej. W tej grupie chorych inhibitory aromatazy wykazują wiekszą niz tamoksyfen aktywnośc w zakresie zwiekszenia odsetka odpowiedzi bezpośrednich i poprawy „operacyjności”. Nie ma natomiast danych co do wiekszej korzyści z ich zastosowania w zakresie calkowitego czasu przezycia. Hormonoterapia przedoperacyjna u chorych przed menopauzą jest przedmiotem kontrowersji. Brakuje takze danych dotyczących bezpośredniego porownania skuteczności chemioterapii i hormonoterapii przedoperacyjnej. Celem pracy jest przegląd biezącego piśmiennictwa dotyczącego hormonoterapii przedoperacyjnej u chorych na raka piersi.

[Transmembrane transporters ABCC - structure, function and role in multidrug resistance of cancer cells].

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.