Can vitamin A modify the activity of docetaxel in MCF-7 breast cancer cells?

Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. On the other hand, the vitamin A family compounds play the essential roles in many biological processes in mammary gland. The aim of our study was to investigate the effect of all-trans retinol, carotenoids (beta-carotene, lycopene) and retinoids (9-cis, 13-cis and all-trans retinoic acid) on the activity of docetaxel and to compare these effects with the estradiol and tamoxifen actions on human ER(+) MCF-7 breast cancer cell line. The evaluation was based on [3H] thymidine incorporation and the proliferative activity of PCNA and Ki 67 positive cells. In our study, the incorporation of [3H] thymidine into cancer cells was inhibited to 50% by 0.2, 0.5 and 1 microM of docetaxel in the 24-hour culture and addition of estradiol (0.001 microM) didn't influence the results. However, addition of tamoxifen caused a statistically significant decrease of the percentage of the proliferating cells in the culture medium with 0.2 and 0.5 microM of docetaxel (38.99 +/- 2.84%,

The influence of chemotherapy on bone marrow in patients with chronic lymphocytic leukaemia

In chronic lymphocytic leukaemia (CLL) bone marrow trephine biopsy (BMT) is not required for diagnosis but can have a significant prognostic value and can be used for the detection of the minimal residual disease (MRD) and for assessment of the effectiveness of the treatment applied. The aim of the study was to evaluate the morphological changes in bone marrow after treatment with purine nucleoside analogues cladribine and fludarabine. Bone marrow trephine biopsy was taken routinely from 15 patients with CLL. Bone marrow trephine biopsy was performed on every patient before as well as after chemotherapy. The number of cell elements of the marrow (the degree of atrophy), the patterns of bone marrow infiltration, the presence of reticulin and collagen fibres and the disturbances in bone marrow stroma were assessed. The infiltration of bone marrow by neoplastic cells was observed in all the patients before administration of chemotherapy. The infiltration was followed by an increase in the number of reticulin fibres. After the treatment a regression of the reticulin fibres was observed with the lessening of the infiltration. After the treatment the levels of marrow infiltrate were decreased. Increased hypoplasia of the bone marrow was observed after the chemotherapy

The influence of the vascularisation of the follicular thyroid nodules on the proliferative activity of the follicular cells

The enlargement of the thyroid is, in general, benign in origin and due to nodular goitre. Follicular cellular proliferation of thyroid nodules has been increasingly observed recently. With fine needle aspiration biopsy (FNAB) this is classified as a follicular tumour. These lesions present various patterns of vascularisation in ultrasound examination. The aim of the study was to establish the relation between follicular nodule vascularisation and the proliferative activity of various types of follicular cell. According to the manner of proliferation, patients were divided into groups as follows: (I) patients with hyperplastic nodules (46 cases), (II) patients with follicular adenoma (42 cases), and (III) patients with follicular cancer (9 cases). In each case B-mode sonography, Power Doppler, sonographically guided FNAB (S-FNAB), morphological examination and morphometry were performed. The proliferative activity was detected with immunohistochemical methods (PCNA, Ki 67 and MPM2) to determine the so-called “proliferative index”. The study revealed increased proliferative activity in tumours of malignant origin and increased vascularisation in coexistence with increased proliferation of the follicular cells. As assessed by Power Doppler, an increased flow pattern in the centre of the nodules correlates with increased proliferative activity. The results suggest that Power Doppler examination could be helpful in selecting nodules for FNAB, especially in multinodular goitre

Histomorphometric study of megakaryocytes in bone marrow in selected myeloproliferative and lymphoproliferative diseases

The aim of the study was an estimation of the histomorphometry of megakaryocytes (MK) in bone marrow in selected myeloproliferative and lymphoproliferative diseases. Bone marrow specimens were obtained by trephine biopsies from 41 patients with polycythaemia rubra vera (PV), idiopathic myelofibrosis (MF), chronic lymphocytic leukaemia (CLL), hairy cell leukaemia (HCL) and diffuse large B-cell lymphoma (L). Morphometric evaluation was performed using a standard program set MicroImage (OLYMPUS). The greatest number of typical nucleated MK, "naked" nuclei, anucleated cytoplasmic fragments and the largest area were found in PV. The circular deviation factor of MK and their nuclei increased in all cases. The greatest number of clusters was observed in PV and HCL. A significant increase in the number of dysplastic and "naked" nuclei of MK was noted in all selected haematological diseases. The presence of neoplastic cells in bone marrow increased the morphological changes in MK. Quantitative and morphometrical significant differentiation of MK in separate microscopic field in the same slides confirms the necessity of performing trephine biopsies in each patient with haematological disorders

Vitamin A family compounds, estradiol, and docetaxel in proliferation, apoptosis and immunocytochemical profile of human ovary endometrioid cancer cell line CRL-11731.

Endometrioid carcinoma represents approximately 10% of cases of the malignant ovarian epithelial tumors. According to literature, the vitamin A (carotenoids and retinoids) plays an essential role in cell proliferation, differentiation and apoptosis in both normal and neoplastic ovarian tissues. Apart from that, the retinoids alter a cytotoxic effect of chemiotherapeutics, i.e. docetaxel, on ovarian cancer cell lines. Retinoids act on cancer cells throughout different mechanism than taxanes, so they may be the potential candidates for the new treatment strategies of ovarian cancer. The aim of the study was to determine the effects of vitamin A family compounds (retinol, beta-carotene, lycopene, all-trans -, 9-cis - and 13-cis retinoic acid) on the growth and proliferation of CRL-11731 endometrioid ovary cancer cell line and on docetaxel and estradiol activity in this culture. The assay was based on [3H] thymidine incorporation and the proliferative activity of PCNA- and Ki 67-positive cells. The apoptotic index and expression of the Bcl-2 and p53 antigens in CRL-11731 cells were also studied. Among vitamin A family compounds retinol and carotenoids, but not retinoids, inhibited the growth of cancer cells in dose dependent manner. Only the concentration of 100 muM of docetaxel inhibited incorporation [3H] thymidine into CRL-11731 cancer cells. Retinol (33.4%+/-8.5), carotenoids (beta-carotene 20 muM 4.7%+/-2.9, 50 muM 2.2%+/-0.9; lycopene 10 muM 7.6%+/-0.8, 20 muM 5.2%+/-2.5, 50 muM 2.9%+/-1.2), and 13-cis retinoic acid (19.7%+/-2.2) combined with docetaxel (100 muM) significantly decreased the percentage of proliferating cells (

Angiogenesis in gliomas.

Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination has a great prognostic value. The aim of the study was to assess the vascularisation of chosen brain gliomas and to estimate how it is correlated with tumour histological type, malignancy grade, location and size, and with age and sex of patients. Tumour vascularisation analysis was based on the determination of microvascular proliferation (MVP) and microvessel density (MVD). Microvascular proliferation was measured with immunohistochemical methods using mouse monoclonal antibodies to detect cell proliferation antigens. The following antibodies were used Ki-67 and PCNA (DAKO). Identification of vessels was performed by CD31 antibody and anti-human von Willebrand factor (DAKO). The highest microvascular proliferation and microvascular density were observed in multiform glioblastomas and the lowest in oligodendrogliomas. Significant correlation was observed between the vascularisation and malignancy grade

Assessment of expression of selected Bcl-2 family proteins in lymphoid infiltration in patients with B-cell chronic lymphocytic leukaemia treated with nucleoside analogues.

B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by clonal growth and accumulation of mature lymphoid cells due to disturbance in genetically regulated form of cell death called apoptosis. The intrinsic mechanism of apoptosis is controlled by Bcl-2 family proteins. Purine nucleoside analogues induce the apoptosis in cells in a state of quiescence. The aim of the study was to assess expression of selected Bcl-2 family proteins in neoplastic infiltration in bone marrow in patients with B-CLL treated with nucleoside analogues. The study comprised examination of bone marrow obtained routinely by trephine biopsy from 18 patients with B-CLL diagnosed before administration of purine nucleoside analogues treatment and after its completion. Expression of Bcl-2, Bcl-x and Bax proteins was examined. Lymphoid cells in bone marrow were present in all patients before administration of treatment. After treatment in two patients bone marrow was infiltrated in diffuse pattern, whereas other patients presented nodular pattern of infiltration. The difference between stage of infiltration before and after treatment was statistically significant (

The effect of levothyroxine on the proliferative activity of the thyroid follicular cells

Wstęp: Farmakologiczne leczenie nietoksycznego wola guzkowego lewotyroksyną wciąż pozostaje sprawą dyskusyjną. Celem pracy było określenie wpływu lewotyroksyny na aktywność proliferacyjną komórek pęcherzykowych tarczycy. Materiał i metody: Materiał cytologiczny uzyskano metodą biopsji aspiracyjnej cienkoigłowej (BAC) wykonanej pod kontrolą USG, przed i 6 miesięcy po leczeniu lewotyroksyną, od 32 kobiet w wieku 34-69 lat będących w stanie eutyreozy. Pacjentki podzielono na dwie grupy wiekowe: przed 45. rokiem życia (14 chorych) i po 45. roku życia (18 chorych). Aktywność proliferacyjną komórek pęcherzykowych oceniono poprzez określenie indeksu proliferacyjnego (PI, proliferative index), stanowiącego odsetek komórek pęcherzykowych z dodatnią reakcją z przeciwciałem Ki-67. Ocenę mikroskopową przeprowadzono, używając komputerowego programu morfometrycznego MicroImage InCD UDF (Olympus). Wyniki: Po 6 miesiącach leczenia wartość indeksu proliferacyjnego była znamiennie statystycznie niższa w obu badanych grupach (8,59 &plusmn; 3,07 vs. 6,51 &plusmn; 1,91; p < 0,001 u kobiet w wieku poniżej 45 lat i 7,72 &plusmn; 1,83 vs. 5,09 &plusmn; 1,51, p < 0,001 w starszej grupie wiekowej). Wnioski: Wyniki przeprowadzonej pracy wskazują, że lewotyroksyna wpływa na aktywność proliferacyjną komórek pęcherzykowych tarczycy, szczególnie u kobiet w wieku okołomenopauzalnym.Introduction: Pharmacological treatment of non-toxic nodular goitre with levothyroxine has caused a discussion about its effectiveness and safety. The aim of the study was to examine the influence of levothyroxine on the proliferative activity of the thyroid follicular cells. Material and methods: Cytological material was obtained from 32 euthyroid females, aged 34-69 years, by USG-guided Fine-Needle Aspiration Biopsy (FNAB), before and after 6 months treatment with levothyroxine. The patients were divided into 2 age groups: up to 45 years (14 patients) and above 45 years (18 females). Proliferative activity of the follicular cells was assessed by the proliferative index (PI), representing the percentage of follicular cells with positive reaction with the antibody Ki-67. Microscopic evaluation was carried out using morphometric computer system MicroImage InCD UDF (Olympus). Results: After 6-months of treatment IP values decreased significantly in both groups studied (8.59 &plusmn; 3.07 vs 6.51 &plusmn; &plusmn; 1.91; p < 0.001 in females aged < 45 years and 7.72 &plusmn; 1.83 vs 5.09 &plusmn; 1.51; p < 0.001 in the older group). Conclusion: Our results indicate that levothyroxine has an influence on the proliferative activity of the thyroid follicular cells, particularly in post-menopausal women

Can vitamin A modify the activity of docetaxel in MCF-7 breast cancer cells?

Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. On the other hand, the vitamin A family compounds play the essential roles in many biological processes in mammary gland. The aim of our study was to investigate the effect of all-trans retinol, carotenoids (beta-carotene, lycopene) and retinoids (9-cis, 13-cis and all-trans retinoic acid) on the activity of docetaxel and to compare these effects with the estradiol and tamoxifen actions on human ER(+) MCF-7 breast cancer cell line. The evaluation was based on [3H] thymidine incorporation and the proliferative activity of PCNA and Ki 67 positive cells. In our study, the incorporation of [3H] thymidine into cancer cells was inhibited to 50% by 0.2, 0.5 and 1 microM of docetaxel in the 24-hour culture and addition of estradiol (0.001 microM) didn't influence the results. However, addition of tamoxifen caused a statistically significant decrease of the percentage of the proliferating cells in the culture medium with 0.2 and 0.5 microM of docetaxel (38.99 +/- 2.84%, p&lt;0.01 and 40.67 +/- 5.62%, p&lt;0.01) in comparison to the docetaxel only group. The above-mentioned observations were also confirmed with the use of the immunohistochemical investigations. Among the examined vitamin A family compounds, the simultaneous application of beta-carotene (0.1 microM) and docetaxel (0.2 microM) resulted in a statistically significant reduction in the percentage of proliferating cells (40.25 +/- 14.62%, p&lt;0.01). Lycopene (0.1 microM), which stimulates the growth of breast cancer cells in a 24-hour culture, had an inhibitory effect (42.97 +/- 9.58%, p&lt;0.01) when combined with docetaxel (0.2 microM). Although, beta-carotene and lycopene belong to the different chemical groups, they surprisingly had a similar inhibitory influence on both growth and proliferation of MCF-7 breast cancer cells when combined with docetaxel. The application of docetaxel either with beta-carotene or lycopene had comparable inhibitory effect on breast cells growth and proliferation as tamoxifen. Therefore, it may suggest a possible important role of these carotenoids in the breast cancer therapy in women especially when docetaxel is applied