Aflatoxin B1-induced changes of glutathione-S-transferase activity in the plasma and liver of the rat

The influence of low doses of aflatoxin B1 (AFB1) and partial hepatectomy (PH) on glutathione-S-transferase (GST) activity was studied in the plasma and liver of the rat. Methods. The animals were divided into four groups. The first (I) and the second (II) group were treated with AFB1 freshly dissolved in dimethyl sulphoxide (DMSO), and administered as a single intraperitoneal dose of 50 mg/rat 24 hrs after the rats had undergone either sham operation or, 40% PH, respectively. The third group (III) of animals was treated with a total dose of 1 mg AFB1 - 5 days per week during a period of 8 weeks. The non-treated animals were used as controls (C). Results. We observed a significant increase of GST activity in the plasma of all experimental groups compared to the controls (C), (p<0.02 to p<0.005). In the liver, the GST activity of all experimental groups was also significantly increased, compared to the controls (from p<0.02 to p<0.005). Conclusion. The administration of both single and multiple doses of AFB1 led to long term increase of GST activity in the rat plasma and liver, and partial hepatectomy had no significant effect on this phenomenon.Ispitivan je uticaj niskih doza aflatoksina B1 (AFB1) i parcijalne hepatektomije (PH) na aktivnost glutation-S-transferaze (GST) u plazmi i jetri pacova. Metode. Životinje su podeljene u četiri grupe. Prva (I) i druga (II) grupa su tretirane AFB1 prethodno sveže rastvaranim u dimetilsulfoksidu (DMSO) i davanim u jednoj intraperitonealnoj dozi od 50 mg po pacovu (24 časa posle izvršene lažne operacije ili 40% PH). Treća grupa (III) bila je tretirana ukupnom dozom od 1 mg AFB1, pet puta nedeljno tokom osam nedelja. Životinje koje nisu tretirane predstavljale su kontrolnu grupu (C). Rezultati. Značajno povećanje GST aktivnosti (p<0,02 - p<0,005) u poređenju sa kontrolnom grupom, utvrđeno je i u plazmi i u jetri svih ispitivanih grupa pacova. Zaključak. Dobijeni rezultati pokazuju da jednokratna, kao i višekratna primena niskih doza AFB1 dovodi do dugotrajne indukcije aktivnosti GST u plazmi i jetri pacova, te da parcijalna hepatektomija nema veći uticaj na ovaj fenomen.nul

Aflatoxin B1-induced changes of glutathione-S-transferase activity in the plasma and liver of the rat

The influence of low doses of aflatoxin B1 (AFB1) and partial hepatectomy (PH) on glutathione-S-transferase (GST) activity was studied in the plasma and liver of the rat. Methods. The animals were divided into four groups. The first (I) and the second (II) group were treated with AFB1 freshly dissolved in dimethyl sulphoxide (DMSO), and administered as a single intraperitoneal dose of 50 mg/rat 24 hrs after the rats had undergone either sham operation or, 40% PH, respectively. The third group (III) of animals was treated with a total dose of 1 mg AFB1 - 5 days per week during a period of 8 weeks. The non-treated animals were used as controls (C). Results. We observed a significant increase of GST activity in the plasma of all experimental groups compared to the controls (C), (p<0.02 to p<0.005). In the liver, the GST activity of all experimental groups was also significantly increased, compared to the controls (from p<0.02 to p<0.005). Conclusion. The administration of both single and multiple doses of AFB1 led to long term increase of GST activity in the rat plasma and liver, and partial hepatectomy had no significant effect on this phenomenon.Ispitivan je uticaj niskih doza aflatoksina B1 (AFB1) i parcijalne hepatektomije (PH) na aktivnost glutation-S-transferaze (GST) u plazmi i jetri pacova. Metode. Životinje su podeljene u četiri grupe. Prva (I) i druga (II) grupa su tretirane AFB1 prethodno sveže rastvaranim u dimetilsulfoksidu (DMSO) i davanim u jednoj intraperitonealnoj dozi od 50 mg po pacovu (24 časa posle izvršene lažne operacije ili 40% PH). Treća grupa (III) bila je tretirana ukupnom dozom od 1 mg AFB1, pet puta nedeljno tokom osam nedelja. Životinje koje nisu tretirane predstavljale su kontrolnu grupu (C). Rezultati. Značajno povećanje GST aktivnosti (p<0,02 - p<0,005) u poređenju sa kontrolnom grupom, utvrđeno je i u plazmi i u jetri svih ispitivanih grupa pacova. Zaključak. Dobijeni rezultati pokazuju da jednokratna, kao i višekratna primena niskih doza AFB1 dovodi do dugotrajne indukcije aktivnosti GST u plazmi i jetri pacova, te da parcijalna hepatektomija nema veći uticaj na ovaj fenomen.nul

Receptor conversion in distant breast cancer metastases

Introduction: When breast cancer patients develop distant metastases, the choice of systemic treatment is usually based on tissue characteristics of the primary tumor as determined by immunohistochemistry (IHC) and/or molecular analysis. Several previous studies have shown that the immunophenotype of distant breast cancer metastases may be different from that of the primary tumor (receptor conversion), leading to inappropriate choice of systemic treatment. The studies published so far are however small and/or methodologically suboptimal. Therefore, definite conclusions that may change clinical practice could not yet be drawn. We therefore aimed to study receptor conversion for estrogen receptor alpha (ER alpha), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in a large group of distant (non-bone) breast cancer metastases by re-staining all primary tumors and metastases with current optimal immunohistochemical and in situ hybridization methods on full sections. Methods: A total of 233 distant breast cancer metastases from different sites (76 skin, 63 liver, 43 lung, 44 brain and 7 gastro-intestinal) were IHC stained for ER alpha, PR and HER2, and expression was compared to that of the primary tumor. HER2 in situ hybridization (ISH) was done in cases of IHC conversion or when primary tumors or metastases showed an IHC 2+ result. Results: Using a 10% threshold, receptor conversion by IHC for ER alpha, PR occurred in 10.3%, 30.0% of patients, respectively. In 10.7% of patients, conversion from ER+ or PR+ to ER-/PR- and in 3.4% from ER-/PR- to ER+ or PR+ was found. Using a 1% threshold, ER alpha and PR conversion rates were 15.1% and 32.6%. In 12.4% of patients conversion from ER+ or PR+ to ER-/PR-, and 8.2% from ER-/PR-to ER+ or PR+ occurred. HER2 conversion occurred in 5.2%. Of the 12 cases that showed HER2 conversion by IHC, 5 showed also conversion by ISH. One further case showed conversion by ISH, but not by IHC. Conversion was mainly from positive in the primary tumor to negative in the metastases for ER alpha and PR, while HER2 conversion occurred equally both ways. PR conversion occurred significantly more often in liver, brain and gastro-intestinal metastases. Conclusions: Receptor conversion by immunohistochemistry in (non-bone) distant breast cancer metastases does occur, is relatively uncommon for ER alpha and HER2, and is more frequent for PR, especially in brain, liver and gastrointestinal metastase

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Differentiated expression of estrogen receptors (ER) and progesterone receptors (PgR) in ductal breast cancers.

Contents of estrogen receptors (ER) and progesterone receptors (PgR) in cells of breast cancers represent strong predictive factors. The higher is the contents of ER and PgR in breast cancer, the higher is a probability of obtaining a response to hormonal therapy and prognosis for the patient is better. In a routine manner, all tumours of mammary gland are subjected to evaluation of ER and PgR expression using immunohistochemistry. Forty ductal breast cancers (pT2N0) were subjected to an immunohistochemical evaluation (IHC) aimed at detection of ER and PgR expression. From every tumour three samples were taken for immunohistochemical studies: the lateral one from the side of axilla (ER-1; PgR-1); the median one (ER-2; PgR-2) and the medial one from the side of sternum (ER-3; PgR-3). The levels of both ER and PgR expression proved to be highly differentiated between the medial zone of the tumour and its periphery. The distinct expression of ER and PgR in ductal breast cancers, dependent on evaluated zone of the tumour, confirms its heterogeneous character and exerts an effect on the type of applied treatment