Can pumpkin save us of doxorubicin induced cardiotoxicity? / ¿Puede la calabaza salvarnos de la cardiotoxicidad inducida por doxorrubicina?

SUMMARY: Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control - S; NADES - N; Doxorubicin - Dox; Carotenoids - Car; CardiofortIN - CF; NADES-Doxorubicin - N-Dox; Carotenoids-Doxorubicin - Car-Dox; CardiofortIN-Doxorubicin - CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.

La doxorrubicina (DOX) es uno de los fármacos necesarios para el tratamiento de los 10 tipos más comunes de cáncer. El principal efecto adverso que limita el uso clínico de DOX es la cardiotoxicidad. Debido a que los datos de la literatura indican un papel protector de los carotenoides en la toxicidad inducida por doxorrubicina, en nuestro estudio comparamos el efecto cardioprotector de una mezcla de carotenoides de calabaza y una preparación antioxidante disponible comercialmente. Los animales se distribuyeron en 8 grupos (Control - S; NADES - N; Doxorrubicina - Dox; Carotenoides - Car; CardiofortIN - CF; NADES-Doxorrubicina - N-Dox; Carotenoides-Doxorrubicina - Car-Dox; CardiofortIN- Doxorrubicina - CF-Dox). Las secciones histológicas se tiñeron con hematoxilina-eosina (HE) y se analizaron para detectar la presencia de daño miocárdico mediante la puntuación de daño por doxorrubicina (DDS). A partir del homogeneizado de tejido cardíaco se determinó la intensidad de la peroxidación lipídica y la actividad enzimática antioxidante específica (superóxido dismutasa, catalasa, glutatión S-transferasa, glutatión peroxidasa). En los grupos Car-DOX y CF-DOX, la peroxidación lipídica se redujo significativamente en comparación con el grupo DOX. El pre tratamiento de los animales con carotenoides y, en menor medida, con CardiofortlN condujo a una mayor actividad de las enzimas antioxidantes, en comparación con el grupo DOX. Al ser pre tratados con carotenoides, solo el 50 % de los animales tenían algún grado de daño miocárdico y ningún animal tenía daño extenso. El pre tratamiento con CardiofortIN mostró un efecto protector menor. El pre tratamiento con extracto de carotenoides redujo significativamente el DDS, por lo que el grupo Car-DOX mostró cambios equivalentes a un daño miocárdico leve. Aunque el pre tratamiento con CardiofortIN redujo los valores de la puntuación DDS, los animales aún tenían un nivel moderado de daño al miocardio. Este estudio in vivo y sus hallazgos indican que los carotenoides extraídos de la calabaza pueden ser un agente cardioprotector prometedor contra la cardiotoxicidad inducida por doxorrubicina, al menos en parte mediada por la inhibición del estrés oxidativo inducido por DOX.

Are statins a risk factor in patients with atherosclerosis? / ¿Son las estatinas un factor de riesgo en pacientes con aterosclerosis?

SUMMARY: Statins inhibit cholesterol synthesis, but also have other pleiotropic effects. There are indications that they affect macrophage survival trough the regulation of apoptosis. We analyzed 50 samples of aortic wall, selected based on statins in patients' therapy (n=25, Th-S group) or statin-free therapy (n=25, Th-nonS group). Each group had 5 samples of healthy aortic tissue, 10 samples of mild and 10 samples of severe atherosclerotic changes in aortic wall. Tissue was stained with hematoxylin-eosin and immunohistochemical methods (anti-Bcl-2 antibody). Presence of Bcl2-positive macrophages (Bcl-2+ MP) was determined semiquantitatively, and data were processed in Microsoft Excell and IMB SPSS 23 Statistics. 60 % of patients in the Th-S group had a mild increase of Bcl-2+ MP The use of statins leads to a significantly more frequent increase in Bcl2+ macrophages in the intima of the healthy aortic tissue. Analysis of all aortic samples with pathohistological diagnosis showed that statin therapy was statistically significantly more often leading to a markedly increased presence of Bcl-2+ MP. In the media, all samples of the Th-S group have a mild increase of Bcl-2+ MP, and in adventitia 40 % of patients. The use of statins more often leads to a markedly increased presence of Bcl-2+ MP in aortic tissue with diagnosed mild and severe atherosclerosis. In samples of severe atherosclerosis, statins lead to a markedly increased presence of Bcl-2+ MP in the parts of the plaque towards the intima and towards the media. Statins lead to an increased presence of Bcl-2+ macrophages, prolong their life, both in healthy and atherosclerotic altered aortic tissue. This indicates potentiation of inflammation and damage to the aortic wall, and calls into question the positive effect of statins on the aortic wall with atherosclerosis.

RESUMEN: Las estatinas inhiben la síntesis de colesterol, pero también tienen otros efectos pleiotrópicos. Hay indicios de que afectan la supervivencia de los macrófagos a través de la regulación de la apoptosis.Se analizaron 50 muestras de pared aórtica, seleccionadas en base a estatinas en tratamiento de pacientes (n=25, grupo Th-S) o en tratamiento libre de estatinas (n=25, grupo Th- nonS). Cada grupo tenía 5 muestras de tejido aórtico sano, 10 muestras de cambios ateroscleróticos leves y 10 muestras de cambios ateroscleróticos severos en la pared aórtica. El tejido se tiñó con hematoxilina-eosina y métodos inmunohistoquímicos (anticuerpo anti-Bcl-2). La presencia de macrófagos positivos para Bcl2 (Bcl- 2+ MP) se determinó semicuantitativamente y los datos se procesaron en Microsoft Excell e IMB SPSS 23 Statistics. El 60 % de los pacientes del grupo Th-S tuvo un aumento leve de Bcl-2+ MP. El uso de estatinas conduce a un aumento significativamente más frecuente de macrófagos Bcl2+ en la íntima del tejido aórtico sano. El análisis de todas las muestras aórticas con diagnóstico anatomopatológico mostró que la terapia con estatinas fue significativamente más frecuente desde el punto de vista estadístico, lo que condujo a una presencia marcadamente mayor de Bcl-2+ MP. En los medios, todas las muestras del grupo Th-S tienen un leve aumento de Bcl-2+ MP, y en adventicia en el 40 % de los pacientes. El uso de estatinas con mayor frecuencia conduce a una presencia marcadamente mayor de MP Bcl-2+ en el tejido aórtico con aterosclerosis leve y grave diagnosticada. En muestras de aterosclerosis severa, las estatinas conducen a una presencia aumentada de Bcl-2+ MP en las partes de la placa hacia la íntima y hacia la media. Las estatinas conducen a una mayor presencia de macrófagos Bcl-2+, prolongan su vida, tanto en tejido aórtico sano como aterosclerótico alterado. Esto indica la potenciación de la inflamación y el daño a la pared aórtica y pone en duda el efecto positivo de las estatinas en la pared aórtica con aterosclerosis.

Tumour-to-tumour Metastasis: Cutaneous Melanoma Metastasizing to Leiomyoma Uteri.

The incidence of melanoma is increasing worldwide. It is known that melanoma frequently progresses to metastatic disease. The aim of this report is to emphasise the metastatic potential of cutaneous melanoma to various body areas, as well as the ability to produce unexpected presentation of the disease. A 48-year female had a myomatous uterus and underwent hysterectomy. At the pathological examination, multiple leiomyomas were diagnosed and in one of them, the metastatic melanoma was found, the later confirmed with immunohistochemical analysis. The medical history revealed that the patient was previously operated two years back due to skin superficial spreading melanoma. The metastasis to uterine leiomyoma was the first site of distant spread. Melanoma is a type of tumour with aggressive and unpredictable behaviour, so metastases to unexpected localisations could occur. A careful examination of patient's body is mandatory, including the remote areas and even benign tumours.

The expression and localization of estrogen receptor beta in hyperplastic and neoplastic prostate lesions.

BACKGROUND/AIM: Benign acini in benign prostatic hyperplasia (BPH) are lined with pseudostratified cylindrical epithelium with a continuous basal cell layer. Adenocarcinoma of the prostate is the most common cancer in men. High gradus-prostatic intraepithelial neoplasia (HGPIN) lesions precede invasive cancer. Prostate adenocarcinoma (PCa) implies a complete absence of basal cells and stromal invasion by malignant acini. Estrogen receptor (ER) is located in nuclei of acinar basal and secretory cells and partially in stromal cells. The aim of this research was to demonstrate and localize ER in BPH and in PCa of different Gleason scores. Considering literature data for ER-beta. expression in different morphologic prostate lesions, it is assumed that there is expression of ER-beta in most moderately differentiated PCa, and that the observed receptor expression is lost with increasing of the Gleason score. METHODS: Four groups of patients were formed: the control with BPH and three experimental groups with PCa of different grades and scores, according to the Gleason grading system. The patients were male of various ages suspected of PCa, based on clinical and laboratory parameters. The study was conducted in a period 2010-2012. None of the patients received prior hormonal therapy. Sextant byopsies with BPH and PCa were treated for ER-beta (Novacastra). Localization and intensity of ER-beta expression is reported through the score: 0 = zero; 1 = < 1%; 2 = 1-10%; 3=11-33%; 4= 34-66%; 5- > 66%. Positive fibroblasts and endothelial cells are used for comparison. RESULTS: ER-beta expression in acinar epithelial cells was the weakest in well-differentiated adenocarcinoma. A decline of ER-beta expression was noticed in malignant lesions of the prostate vs. benign ones. Less differentiated adenocarcinomas showed a decrease of ER-beta expression in basal and in the secretory cells. ER-beta expression in basal cells was stronger than in secretory ones in BPH and well-differentiated adenocarcinoma. CONCLUSION: ER-beta expression was most pronounced in BHP samples and declined in malignant prostate lesions. This finding supports statement on anticiproliferative role of ER-beta in prostatic tissue.

Squamous cell carcinoma in mature cystic teratoma of the ovary.

INTRODUCTION: Malignant transformation is a rare complication of mature cystic teratoma, with squamous cell carcinoma as the most common malignancy (in 75% of cases). In this article we present a case of a well-differentiated squamous cell carcinoma arising in a mature cystic teratoma and discuss the morphological and clinico-pathological features of malignant transformation in teratoma. CASE REPORT: An 80-year-old woman with symptoms of acute abdomen underwent left salpingo-oophorectomy. Gross examination showed a cystic mass measuring 20 cm in diameter, with papillary formation on its internal surface. Histology revealed a well-differentiated squamous cell carcinoma arising in mature cystic teratoma. Squamous epithelium surrounding the tumor was dysplastic. CONCLUSION: Squamous cell carcinoma in mature cystic teratoma is a rare pathologic event and in most cases it is an accidental pathohistological finding.

[Morphology and immunohistochemical studies of ovarian strumal carcinoid].

INTRODUCTION: Teratomas are tumors derived from pluripotent germ cells, and they appear most frequently in ovaries. Strumal carcinoid belongs to the group of monodermal teratomas. Strumal carcinoid is characterized by the presence of carcinoid tumor, intermingled with thyroid tissue. CASE REPORT: A 52-year-old postmenopausal woman was referred to the Department of Gynecology and Obstetrics, Clinical Center of Vojvodina, Novi Sad with complex right adnexal mass for surgery. Laparotomy revealed tumor arising from the right ovary, of firm consistency and intact capsule. On gross examination, yellowish brown tumor was 26 x 17 x 10 cm, with vague nodularity. The cut sections revealed predominantly solid mass with two cystic areas, and one of the cysts showed a tuft of hair. On histopathological examination, the cystic spaces were lined with skin and mucinous epithelium. The solid areas showed a population of monomorphic cells with eosinophilic cytoplasm and nuclei with "salt and pepper" chromatin, arranged in acinar and trabecular patterns, respectively. In addition, focally follicular structures with central eosinophilic colloid-like material were seen. Based on the presence of these two components, a diagnosis of Strumal Carcinoid was made and confirmed on immunohistochemistry. The tumor cells were diffusely immunopositive for synaptophysin, chromogranin, and the follicles including the central coIloid were immunopositive for thyroglobulin and Thyroid transcription factor-1. Neither proliferative or mitotic activity nor capsular or angiolymphatic invasion were noticed. At 3 year follow up the patient was disease free. CONCLUSION: In order to diagnose this rare tumor a team, consisting of a pathologist, surgeon and radiologist, is needed. Diagnosis of strumal carcinoid has to be confirmed on immunohistochemistry.