Carcinosinumproduces phenotypic changes of 4T1 tumor cells in vitro

Considering that there are few published studies that specifically address the exclusive use of Carcinosinumin different potencies and, most of them focused on genotypic and clinical effects, the present study was proposed to identify possible phenotypic changes, including viability, expression of HER-2 and metastatic abilities, using 4T1 cells in vitroas a model. Carcinosinum was tested in different homeopathic potencies (12cH; 30cH; 200cH) mechanically prepared using sterile pure water. The time space between preparing the potencies and using them was 24 hours.The final dilutions were inserted into the culture medium in a volume equal to 10%, at the time of cell seeding. The same succussed vehicle used to prepare the drugs (70% ethanol) diluted 1:100 in sterile pure water was used as control. All treated cells were cultured in 25 mL flasks, with cell density of 5 x 105cells/mL. After 24 hours of treatment, cells were analyzed for apoptosis index using Annexin V kit and the Countess® system. The morphology of 4T1 cells was monitored by staining cell smears with hematoxylin-eosin and Giemsa methods. HER-2 expression was assessed by immunocytochemistry and metalloproteinase activity was assessed by zymography. The determination of the cytokine profile was performed using Cytometric Bead Array (CBA). The samples were evaluated in quadruplicate and the data were analyzed by one-way ANOVA. Carcinosinum30cH presented the highest apoptotic index and reduction of MMP-9-Pro expression; Carcinosinum200cH produced the highest positivity for HER-2 and no specific effect was seen after the treatment with Carcinosinum12cH. No change in cytokine expression was seen among treatments. We conclude that Carcinosinum30cH and 200cH can change phenotypic features important totumor development in vitro. The clinical meaning of these data deserves further investigation.

Synthesis and Anticancer Activity of Novel 2-Phenylindole Linked Imidazolothiazole, Thiazolo-s-triazine and Imidazolyl-Sugar Systems

Novel functionalized 2-phenylindole derivatives, their derived imidazolethione and 1,2,4-triazinethione weresynthesized. The bicyclic compounds thiazoloimidazole and thiazolotriazine compounds in addition to their arylidinederivatives 5-8 were synthesized. Furthermore, a thioglycoside, as well as sugar hydrazone derivatives of theimidazolylindole system, were prepared. Some of the prepared compounds were screened against four cancer celllines and compounds 2, 3a and 10 showed high cytotoxic activities. The imidazolylindol-3-one derivatives 3a showedsignificant cytotoxic effect superior to the reference drug, doxorubicin, against breast adenocarcinoma cell line.

Co-culture of human breast adenocarcinoma cells and human umbilical vein endothelial cells to mimic in vivo tumor microenvironment / 药学学报

The development of tumor tissue is a complicated process, which is closely related to tumor microenvironment. In order to simulate the tumor tissue in vivo, non-contact co-culture of human breast adenocarcinoma cells (MCF-7 cells) and human umbilical vein endothelial cells (HUVECs cells) using transwell cell culture plate was developed in this study. The cell viability, morphology, cell resistance, cell cycle and vascular endothelial growth factor (VEGF) protein content of co-cultured MCF-7 and HUVECs cells were investigated, and compared with those of separately cultivated MCF-7 and HUVECs cells during the same period. Different to the separately cultured MCF-7 and HUVECs cells, co-cultured MCF-7 and HUVECs cells exhibited higher cell viability, deformed cell morphology, lower cell resistance, higher proportion of S and G2/M phases and higher VEGF protein content (about 1.4−2 times). The double cell model via non-contact co-culture of MCF-7 and HUVECs cells constructed in this study could simulate the interaction between tumor cells and tumor vascular endothelial cells in vivo, which may provide a more realistic model for subsequent study of drug release system in the control of breast cancer in vitro.

Células cebadas y sus patrones de expresión del receptor c-kit (CD117) como probables indicadores de metástasis en el adenocarcinoma de mama en humanos / Mast cells and expression patterns of c-kit (CD117) receptor as probable indicators of metastases in human breast adenocarcinoma

El adenocarcinoma de mama es la segunda neoplasia maligna más común en mujeres, solo después del cáncer de pulmón. Este tumor se clasifica histopatológicamente en bien, moderado y poco diferenciado. Además de esta clasificación, los análisis actuales utilizan inmunohistoquímica para identificar receptores hormonales para estrógenos y progesterona (RH) y HER2/neu, esta información permite hacer un pronóstico de respuesta al tratamiento y tiempo de sobrevida. Las células cebadas se han asociado a un mal pronóstico, ya que participan en la angiogénesis y el crecimiento tumoral favoreciendo la metástasis. Esto disminuye la esperanza de vida. También las células cebadas expresan en la membrana plasmática el receptor c-Kit (CD117) que se ha asociado a proliferación celular. En este estudio, se evaluó si existen variaciones en los patrones de expresión de c-Kit en las células cebadas presentes en muestras de adenocarcinoma de mama; y si los distintos patrones del receptor se asocian a la presencia de metástasis linfática. Se utilizaron muestras de adenocarcinoma moderadamente diferenciado, y se analizaron empleando métodos histológicos, histoquímicos e inmunohistoquímicos. Los grupos se clasificaron de acuerdo a su positividad a RH y HER2/neu, y se subclasificaron de acuerdo a la presencia o no de metástasis. Además se realizó un análisis morfométrico de células cebadas y los patrones de expresión de c-Kit. Los grupos con metástasis mostraron mayor cantidad de células cebadas comparados con el grupo control, y su grupo correspondiente sin metástasis. Las células cebadas con patrones de expresión 1 y 3 fueron más abundantes en los grupos con metástasis. En los grupos sin metástasis predominaron las células cebadas con el patrón 2. Los resultados sugieren que el número de células cebadas y los patrones de expresión de c-Kit, podrían ser empleados como indicadores probables, más no definitivos de la presencia de metástasis linfática.

Breast adenocarcinoma is the second most common neoplasm, just after lung cancer in women. According to histopathological features this tumor is classified into well, moderate and poorly differentiated. In addition to this classification, current analysis also use immunohistochemistry to detect estrogen and progesterone receptors (RH), and HER2/neu, this information is useful to make a prognostic in treatment response and survival time. Mast cells have been associated with bad prognosis, because they participate in angiogenesis and tumor growth promoting metastases. This decreases life expectancy. Also mast cells express in the plasmatic membrane the receptor c-Kit (CD117) that is associated to cell proliferation. In this study, we evaluated if there are variations in the expression patterns of c-Kit receptor in mast cells present in breast adenocarcinoma samples; and if expression patterns are associated with the presence of metastases to ganglion. Samples of moderately differentiated adenocarcinoma were evaluated using histological, histochemistry and immunohistochemistry methods. Groups were classified according to their positivity to RH and HER2/neu, and subclassified if presented or not metastases. Also mast cells and expression patterns of c-Kit receptor were analyzed by a morphometric method. Groups with metastases showed higher amount of mast cells, compared with control group and their corresponding group without metastases. Mast cells with expression patterns 1 and 3 were more abundant in all the groups with metastasis. In groups without metastases mast cells with pattern 2 were predominant. Results suggest that the amount of mast cells and the expression patterns of c-Kit could be use as probable indicators, but not definitive of the presence of nodal metastases.

Soybean extracts enriched with free isoflavones promote nitric oxide synthesis and affect the proliferation of breast adenocarcinoma cells

Although soybean isoflavones naturally accumulate in their conjugated forms, the beneficial effects on human health of soybean-containing foods have been credited to their aglycone forms. In the present study we analyzed the effects of a chemical agent, sodium nitroprusside (SNP), in eliciting the exudation of non-conjugated isoflavones from intact soybean seeds, embrionary axes and cotyledons. The isoflavones in the exudates were determined by high performance liquid chromatography and mass spectrometry. The effect of the exudates on the emission of nitric oxide (NO) and on the proliferation of breast carcinoma cells (MCF-7) was also evaluated. SNP elicitation increased the production of the aglycone forms dose- and time-dependently. Exudates of embrionary axes and cotyledons stimulated NO emission and showed biphasic effects on viability of MCF-7 cells. At lower concentrations both extracts presented proliferative effects (10-25%), and at higher concentrations inhibited (15%) cell proliferation. The biphasic effect might be due to the action of isoflavone aglycones in activating estrogen receptors which in turn stimulate the production of NO. Overall, the results suggest that soybean extracts enriched in isoflavone aglycones by elicitation with SNP could be exploited as a functional ingredient in the food industry.

Neurinoma del plexo braquial simulando metastasis de adenocarcinoma de mama / Schwannoma of the brachial plexus resembling a breast adenocarcinoma metastasis

Los neurinomas del plexo braquial son tumores infrecuentes que pueden confundirse con otras lesiones de índole tumoral. Se presenta el caso de una mujer de 40 años, tratada previamente de un adenocarcinoma de mama derecha en el pasado, que en el estudio de extensión realizado 5 años después se detectó una lesión localizada en el plexo braquial derecho. La paciente se encontraba asintomática. El diagnóstico radiológico de presunción fue metástasis de adenocarcinoma mamario. Se realizó un abordaje axilar derecho descubriendo una lesión bien delimitada en el plexo braquial. Con ayuda de la monitorización neurofisiológica intraoperatoria, se observó que la lesión dependía de la rama cubital y se pudo realizar una resección completa preservando la función de dicho nervio. El estudio anatomopatológico confirmó que se trataba de un neurinoma, descartando así la existencia de metástasis. La evolución postoperatoria fue satisfactoria. Seis años después de la intervención no existe recidiva tumoral. En nuestro conocimiento este es el primer caso publicado en la literatura de un neurinoma del plexo braquial dependiente de la rama cubital. La monitorización neurofisiológica intraoperatoria resulta fundamental para abordar este tipo de lesiones con baja morbilidad.

Schwa nomas originating from the brachial plexus, although rare, may be mistaken for another type of tumour. A 40 year-old woman, who had been treated years earlier for a breast adenocarcinoma, showed in the 5-year follow-up magnetic resonance examination a localized lesion in the right brachial plexus. The presumptive radiological diagnosis was a metastasis from the primary adenocarcinoma. Following surgical access via the right axilla, a well-circumscribed mass in the brachial plexus was detected. Under intraoperative electrophysiological guidance, the lesion was observed to depend on the ulnar nerve and its complete resection was possible without compromising nerve function. Histological findings indicated a schwannoma thus ruling out the presence of metastasis. The postoperative development was uneventful and six years after surgery, the patient is to date tumour-free. To the best of our knowledge, this is the first report of a brachial plexus schwannoma arising from the ulnar branch. Intraoperative electrophysiological monitoring is essential for a good surgical outcome.

Metástase de adenocarcinoma de mama no ângulo pontocerebelar / Breast andenocarcinoma metastasis in the cerebello pontire angle

Câncer de mama é a principal neoplasia maligna em mulheres. Apesar de todos os avanços médicos tanto no diagnóstico como na terapêutica, um terço das pacientes com esse tipo de câncer irá morrer em decorrência das metástases. Apesar de tumores no ângulo pontocerebelar (APC) terem uma apresentação clínica com características uniformes, eles representam variedades histopatológicas distintas. Além das metástases, o neurinoma do acústico, meningiomas, cistos epidermoides e neurinomas dos nervos cranianos V, VII, IX, X e XI correspondem, aproximadamente, a 98% dos tumores no APC. Este relato descreve um caso de metástase de adenocarcinoma de mama no APC.

Breast cancer is the main malignant neoplasm in women. Despite all diagnostic and therapeutic advances, one third of the patients with this cancer will die as a result of metastasis. Although tumors in the cerebellopontine angle present with clinical uniform characteristics, they represent distinct histopathological varieties. Besides metastasis, acoustic schwannomas, meningiomas, epidermoidal cysts, and neurinomas of V, VII, IX, X and XI cranialnerves occur in about 98% of the tumors of cerebellopontine angle. This report describes a rare case of breast adenocarcinoma metastasis in the cerebellopontine angle.