Store-independent Orai1-mediated Ca2+ entry and cancer.

Ca2+ channels play an important role in the development of different types of cancer, and considerable progress has been made to understand the pathophysiological mechanisms underlying the role of Ca2+ influx in the development of different cancer hallmarks. Orai1 is among the most ubiquitous and multifunctional Ca2+ channels. Orai1 mediates the highly Ca2+-selective Ca2+ release-activated current (ICRAC) and participates in the less Ca2+-selective store-operated current (ISOC), along with STIM1 or STIM1 and TRPC1, respectively. Furthermore, Orai1 contributes to a variety of store-independent Ca2+ influx mechanisms, including the arachidonate-regulated Ca2+ current, together with Orai3 and the plasma membrane resident pool of STIM1, as well as the constitutive Ca2+ influx processes activated by the secretory pathway Ca2+-ATPase-2 (SPCA2) or supported by physical and functional interaction with the small conductance Ca2+-activated K+ channel 3 (SK3) or the voltage-dependent Kv10.1 channel. This review summarizes the current knowledge concerning the store-independent mechanisms of Ca2+ influx activation through Orai1 channels and their role in the development of different cancer features.

Catalytic functionalization of methane and light alkanes in supercritical carbon dioxide.

The development of catalytic methods for the effective functionalization of methane yet remains a challenge. The best system known to date is the so-called Catalytica Process based on the use of platinum catalysts to convert methane into methyl bisulfate with a TOF rate of 10(-3) s. In this contribution, we report a series of silver complexes containing perfluorinated tris(indazolyl)borate ligands that catalyze the functionalization of methane into ethyl propionate upon reaction with ethyl diazoacetate (EDA) by using supercritical carbon dioxide (scCO2) as the reaction medium. The employment of this reaction medium has also allowed the functionalization of ethane, propane, butane, and isobutane.

[Cutaneous metastases from transitional cell carcinoma of the bladder producing beta-HCG]. / Metástasis cutáneas de un carcinoma transicional vesical productor de beta-HCG.

In spite of the high incidence of transitional cell carcinoma, cutaneous metastases are infrequent, especially when they are the first sign of metastatic spread, with a low survival rate. Thirty five per cent of transitional cell carcinoma of the bladder have ectopic beta- human chorionic gonadotropin (beta-HCG) production. It has been related with high grade tumors, advanced stage, metastatic disease, radioresistent tumors and low survival rate because of its effect as a growth modulator with a probably antagonist action in the apoptotic cascade. We present a thirty six years old woman affected by a transitional cell carcinoma of the bladder producing beta-HCG that showed two cutaneous metastases as first sign of metastatic disease. The exceptional coincidence of these two circumstances announced a very aggressive tumor behaviour and bad prognostic, with a quickly multiple metastatic dissemination including a pericardic metastases.

Kidney androgen-regulated protein transgenic mice show hypertension and renal alterations mediated by oxidative stress.

BACKGROUND: Kidney androgen-regulated protein (KAP), a proximal tubule androgen-regulated gene, codes for a protein of unknown function. METHODS AND RESULTS: To investigate the consequences of KAP overexpression in kidney, we produced KAP transgenic mice and performed microarray expression analyses in kidneys of control and transgenic males. Downregulation of the androgen-sensitive Cyp4A14 monooxygenase gene in KAP transgenic mice prompted us to analyze blood pressure levels, and we observed that transgenic mice were hypertensive. Inhibition of 20-hydroxyeicosatetraenoic acid synthesis by N-hydroxy-N'-(4-n-butyl-2-methylphenyl) formamidine (HET0016) reduced the increased 20-hydroxyeicosatetraenoic acid levels in urine and normalized arterial pressure in transgenic mice, as did the NADPH oxidase inhibitor apocynin. Increased oxidative stress in transgenic mice was demonstrated by (1) enhanced excretion of urinary markers of oxidative stress, 8-iso-prostaglandin F2alpha, 8-hydroxydeoxyguanosine, and thiobarbituric acid-reacting substances; (2) augmented mitochondrial DNA damage and malondialdehyde levels in kidneys; and (3) diminished catalase and glutathione peroxidase activity in transgenic kidneys. Mice exhibited renal defects that included focal segmental glomerulosclerosis, proteinuria, glycosuria, and fibrosis. CONCLUSIONS: Taken together, these results indicate that KAP expression is critical for cardiovascular-renal homeostasis maintenance and that hypertension is associated with increased oxidative stress. This is the first report showing that overexpression of an androgen-regulated, proximal tubule-specific gene induces hypertension. These observations may shed light on the molecular pathophysiology of gender differences in the prevalence and severity of hypertension and chronic renal disease.

Metástasis cutáneas de un carcinoma transicional vesical productor de β-HCG / Cutaneous metastases from transitional cell carcinoma of the bladder producing β-HCG

A pesar de la alta incidencia de carcinoma transicional vesical, la aparición de metástasis cutáneas es infrecuente, más aún como primera manifestación de diseminación metastásica, asociándose a una pobre supervivencia. La producción ectópica de beta-gonadotropina coriónica humana (β-HCG) ocurre en un 35% de los carcinomas transicionales vesicales y se ha correlacionado con tumores de alto grado, estadios avanzados, enfermedad metastásica, falta de respuesta a la radioterapia y pobre supervivencia, en virtud de su efecto regulador del crecimiento tumoral por un probable efecto antagonista sobre receptores de la cascada apoptótica. Presentamos el caso de una paciente de 36 años con carcinoma transicional de vejiga productor de β-HCG que presentó dos metástasis cutáneas como primer signo de enfermedad a distancia. Ambas circunstancias asociadas de forma excepcional identificaron un comportamiento muy agresivo del tumor y su mal pronóstico, desarrollando a corto plazo un estallido metastático a múltiples niveles incluyendo una metástasis pericárdica (AU)

In spite of the high incidence of transitional cell carcinoma, cutaneous metastases are infrequent, especially when they are the first sign of metastatic spread, with a low survival rate. Thirty five per cent of transitional cell carcinoma of the bladder have ectopic beta- human chorionic gonadotropin (β-HCG) production. It has been related with high grade tumors, advanced stage, metastatic disease, radio resistent tumors and low survival rate because of its effect as a growth modulator with a probably antagonist action in the apoptotic cascade.We present a thirty six years old woman affected by a transitional cell carcinoma of the bladder producing β-HCG that showed two cutaneous metastases as first sign of metastatic disease. The exceptional coincidence of these two circumstances announced a very aggressive tumor behaviour and bad prognostic, with a quickly multiple metastatic dissemination including a pericardic metastases (AU)

[Synchronous metastases of the spermatic cord from papillary renal cell carcinoma]. / Carcinoma renal papilar con metástasis sincr6nica en el cordón espermático.

Papillary renal cell carcinoma has been related with higher survival rate and lower metastatic cancer mortality rate than clear renal cell carcinoma. We present an aggressive case related to unusual features for this histological type, like a tumor size higher than ten cm, great perirrenal fat and suprarenal gland infiltration, tumoral thrombosis of the infrahepatic cava vein, retroperitoneal adenopatic tumoral infiltration, high nuclear grade and synchronous solitary distant organ metastases of the right spermatic cord, finding three previous cases in the literature with this last feature. Prognostic implication of the papillary renal cell carcinoma type is unclear in cases like this, so probably we need better molecular and cytogenetic studies to get a correct classification of this histological type.

Carcinoma renal papilar con metástasis sincrónica en el cordón espermático / Synchronous metastases of the spermatic cord from papillary renal cell carcinoma

El carcinoma de células renales papilar (CCRP) se ha relacionado con porcentajes de supervivencia superiores y tasas de mortalidad por cáncer metastático inferiores respecto al carcinoma de células renales convencional. Presentamos un caso de comportamiento agresivo de acuerdo a la suma de características infrecuentes para esta variante histológica, como el tamaño tumoral superior a 10 cm, la infiltración severa de la grasa perirrenal y de la glándula suprarrenal homolateral, la trombosis tumoral de la vena renal y de la vena cava infradiafragmática, la afectación adenopática retroperitoneal, un alto grado nuclear y la asociación en el momento del diagnóstico de una metástasis a distancia única sincrónica en el cordón espermático derecho, habiéndose comunicado esta última circunstancia en tres casos previos. La diferenciación pronóstica de la variante papilar resulta controvertida ante casos de este tipo, planteando la necesidad de obtener mejores perfiles diferenciales citogenéticos y moleculares para la clasificación de esta entidad histológica

Papillary renal cell carcinoma has been related with higher survival rate and lower metastatic cancer mortality rate than clear renal cell carcinoma. We present an aggressive case related to unusual features for this histological type, like a tumor size higher than ten cm, great perirrenal fat and suprarenal gland infiltration, tumoral thrombosis of the infrahepatic cava vein, retroperitoneal adenopatic tumoral infiltration, high nuclear grade and synchronous solitary distant organ metastases of the right spermatic cord, finding three previous cases in the literature with this last feature. Prognostic implication of the papillary renal cell carcinoma type is unclear in cases like this, so probably we need better molecular and cytogenetic studies to get a correct classification of this histological type

[Primary hepatic actinomycosis]. / Actinomicosis hepática primaria.

Primary hepatic actinomycosis is a rare infection that can clinically be confused with hepatic pyogenous abscesses or neoproliferative processes. We present the case of a 71-year-old man who had previously undergone total gastrectomy for gastric adenocarcinoma. After 4 years of favorable clinical course he presented a space-occupying lesion in the right hepatic lobe. Diagnostic tests were nonspecific and the diagnosis was confirmed by histological study of a biopsy of the lesion obtained through laparotomy. Prolonged antibiotic treatment produced a complete response. The etiopathogenesis and diagnostic-therapeutic options of hepatic actinomycosis are reviewed.

Splenic and adrenal lymphangiomatosis.

Lymphangiomatosis is a rare syndrome that can affect different organs, although simultaneous splenic and adrenal involvement is exceptional. We report the case of a young female with a symptomatic massive splenomegaly and no-nhypersecreating bilateral adrenal masses incidentally discovered that represented a diagnostic challenge. The management of adrenal incidentalomas is controversial, as the presence of large sized bilateral masses are highly indicative of malignancy. Despite the different diagnostic techniques available, it is sometimes impossible to reach an accurate preoperative diagnosis. Elective splenectomy and left adrenalectomy were performed, preserving the functioning of the right adrenal gland, radiologically similar to the left one, to prevent the development of definitive adrenal insufficiency. Postoperative evolution has been favourable without initial increase of the size of the right adrenal lesion. However, the persistence of this mass obligated long-term follow-up and shall assist us in better understanding the behavior of this bening lesion.

Miofibroblastoma de mama en un paciente varón / Myofibroblastoma of the breast in a male patient

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Influence of remote substituents on the equatorial/axial selectivity in the monooxygenation of methylene C--H bonds of substituted cyclohexanes.

The reactivity of individual C--H bonds in the methyl(trifluoromethyl)dioxirane TFDO oxygenation of stereogenic methylene groups in conformationally homogeneous monosubstituted cyclohexanes (2) has been determined. The unexpectedly high occurrence of O-atom insertion into C--H(ax) bonds suggests an in plane trajectory attack in the oxygenation while the diastereoselectivity of the reaction is qualitatively interpreted on the basis of the distinct hyperconjugative stabilization by the substituent of diastereomeric transition states due to long-range through bond interactions.

Susceptibility of Spanish populations of the corn borers Sesamia nonagrioides (Lepidoptera: Noctuidae) and Ostrinia nubilalis (Lepidoptera: Crambidae) to a Bacillus thuringiensis endotoxin.

Baseline susceptibility to the Cry1Ab delta-endotoxin from Bacillus thuringiensis (Berliner) was determined for four populations of Sesamia nonagrioides (Lefebvre) and two populations of Ostrinia nubilalis (Hübner) from Spain. This study shows that S. nonagrioides is at least as susceptible as O. nubilalis to B. thuringiensis Cry1Ab protein. We found small differences in susceptibility among the Spanish populations of S. nonagrioides that can be attributed to natural variation, because there are no records of B. thuringiensis products being used on corn crops in Spain. There were no differences in susceptibility to Cry1Ab toxin between the two populations of O. nubilalis.

Massive ovarian oedema.

Eighteen cases of massive ovarian oedema are presented. The age of patients averaged 26 years and 16 presented with an acute abdomen. Hormonal symptoms included virilism in three cases and one with precocious pseudopuberty. Ultrasonographic findings were variable and not diagnostically accurate. When performed, CA 125 levels were not raised. Seventy-two percent of cases occurred in the right ovary and none were bilateral. Torsion occurred in 14 cases. Salpingo-oophorectomy was performed in all cases. To elucidate its pathogenesis, be this either due to intermittent chronic torsion or to a proliferative phenomenon, immunohistochemistry for Ki-67 and PCNA proliferation antigens, alpha-actin and oestrogen and progesterone receptors was performed. The Ki-67 proliferation index ranged between 0% and 3%, demonstrating the low proliferative status of stromal cells. The PCNA indices, however, were unusually high (60% and above). The divergence between these findings is explained by the fact that PCNA positivity may be related to nuclear reparation subsequent to ischaemia. Alpha-actin was consistently positive in stromal cells, reflecting a myofibroblastic transformation of these cells. These findings together with the clinical evidence of torsion in the majority of cases, lead us to consider that ovarian oedema is a reactive, non-proliferative state of specific stromal cells, occurring as a response to torsion and subsequent ischaemia. The stromal cells have positive oestrogen progesterone receptors and may undergo stimulatory changes responsible for the hormonally related symptoms often found associated with massive ovarian oedema.

[Solitary extramedullary plasmocytoma of the nasal fossa and paranasal sinuses]. / Plasmocitomas solitarios extramedulares de fosas nasales y senos paranasales.

The clinical and morphological features of two patients with solitary extramedullary plasmacytomas of paranasal sinus and nasal cavity are presented. Patients only developed local symptomatology without features of multiple myeloma. They were treated with surgical excision and local radiotherapy. This is the treatment of choice recommended for these localized tumors. Microscopically, one tumor contained a well-differentiated plasma cell population, and the other was made up immature cells. Cytoplasmic staining for IgG was showed in both tumors for immunoperoxidase studies. However, no serum monoclone was detected at the time of diagnosis nor later. Currently, they are alive without evidence of disease 20 and 16 months, respectively, after treatment.

[Rhinosporidiosis: presentation of 4 cases]. / Rinosporidiosis: aportación de cuatro casos.

We report 4 cases of rhinosporidiosis in the province of Cáceres. Two had nasal localization and in two ocular conjunctiva was involved. Three patients, two of which came from the same village, had the antecedent of bathing in the same stagnant water. The diagnosis was made by the microscopic observation of characteristic sporangia of Rhinosporidium seeberi in the histopathological study. The lesions did not respond to antibiotic and antiinflammatory treatment. After excision there were no recurrences, and the patients are asymptomatic after 1 1/2 year follow up.