Association of Metastasis with Clinicopathological Data in Mexican Patients with Osteosarcoma, Giant Cell Tumor of Bone and Chondrosarcoma.

BACKGROUND: Bone tumors are neoplasias with a high overall mortality; one of the main factors that reduce survival is their high capacity to develop metastases. It has been reported that finding lung metastases at diagnosis of osteosarcoma (OS), chondrosarcoma (CS) and giant cell tumor of bone (GCTb) is quite common. In this study, we inquire the relationship of metastases caused by these tumors with different clinical and pathological aspects, in order to guide medical personnel in the diagnosis and opportune treatment of metastases or micro metastases. MATERIALS AND METHODS: We collected data of 384 patients with clinical, radiological and histopathological diagnosis of OS, GCTb and CS that attended the National Rehabilitation Institute (INR) during 2006 to 2014. Chi-square and Fisher's exact tests were performed for data analysis. RESULTS: In the three tumor types, the presence of metastases at diagnosis was variable (p=0.0001). Frequency of metastases was 36.7%, 31.7% and 13.2% for OS, CS and GCTb respectively. The average age had no significant difference (p>0.05) in relation to metastases, even so, patients with OS and GCTb and metastases, were older while patients with CS and metastases were younger, in comparison to patients without metastases. Males had a higher frequency of metastases (68.2%, p = 0.09) in contrast to CS and GCTb, in which the metastases was more frequent in women with 51.9% (p = 0.44) and 57.9% (p = 0.56) respectively. Broadly, metastasis was associated with primary tumors located in the femur (44.4%), followed by the tibia (15.6%); metastases was more frequent when primary tumor of GCTb and OS were in the same bones, but were located in the hip (26.3%) for CS. CONCLUSIONS: The frequency of metastases in OS, GCTb and CS is high in our population and is determined by different clinicopathological variables related to the kind of tumor. Further studies are needed in order to evaluate metastases subsequent to diagnosis and associations with survival and clinicopathological factors , as well as to determine the sensitivity and specificity of current methods of detection.

Epidemiological Aspects of Osteosarcoma, Giant Cell Tumor and Chondrosarcoma Musculoskeletal Tumors--Experience of the National Rehabilitation Institute, Mexico City.

BACKGROUND: Primary bone neoplasms are rare, contributing only 0.2% of the global burden of all human malignancies. Osteosarcoma (OS) and chondrosarcoma (CS) are the most common malignancies of bone. The giant cell tumor of bone (GCTb) is a benign tumor with behavior characterized by osteolytic bone destruction. The OS, CS and GCTb affect both sexes, all races and generally have incidence peaks regarding the age of the patient which vary according to the tumor type. We analyzed the incidences of OS, CS and GCTb and their relations with gender and age in patients treated in the National Rehabilitation Institute (INR, for its acronym in Spanish) over a period of nine years. MATERIALS AND METHODS: In the study period, clinic pathological data for 384 patients were obtained with clinical, radiological and histopathological diagnosis for OS, GCTb and CS. Data analysis was performed using the chi-square and Fisher's exact tests. RESULTS: From 2006 to 2014 were recorded 384 cases of bone malignancies in the database of INR. The GCTb had the highest incidence (53.1%), followed by OS (31.3%) and finally the CS (15.6%). The overall average age was 33.6±15.8 years and the overall frequency of gender had a ratio of 1/1.03 male/female. The states with the highest incidence were Distrito Federal and Estado de Mexico with 29.2% and 25.3% respectively. Malignant neoplasms of bone assessed in the course of nine years show three significant increases in 2008, 2011 and 2014 (p=0.14). We found association between sex and tumor type (p=0.03), GCTb and CS predominated in females (54.9% and 56.6% respectively), while for the OS males were most affected (59.1%). Age was different in relation with tumor type (p=0.0001), average age was 24.3±11.2 years for OS, 34.5±13 years for GCTb and 49.2±18.5 years for CS. Furthermore, associations of tumor type with topographic location of the primary tumor (P=0.0001) were found. CONCLUSIONS: In this study we can see that incidence of musculoskeletal tumor in our population is continuously increasing and in nine years an approximately 200% increase of musculoskeletal tumor cases was observed.

The selective inhibition of the D1 dopamine receptor results in an increase of metabolized dopamine in the rat striatum.

Our aim was to study the specific role of the postsynaptic D(1) receptors on dopaminergic response and analyze the metabolized dopamine (DA) in the rat striatum. We used male Wistar rats to evaluate the effects of different doses of a D(1) agonist (SKF-38393) and a D(1) antagonist (SCH-23390), and their co-administration. The levels of DA and L-3, 4-dihydroxyphenylacetic acid (DOPAC) were measured using high performance liquid chromatography. The systemic injection of SKF-38393 alone at 1, 5 and 10 mg/kg did not alter the DA and DOPAC levels or the DOPAC/DA ratio. In contrast, injection of SCH-23390 alone at 0.25, 0.5 and 1 mg/kg significantly increased the DA and DOPAC levels, as well as the DOPAC/DA ratio, compared with the respective control groups. The co-administration of SCH-23390+SKF-38393 did not alter the DA or DOPAC levels, but it did significantly inhibit the SCH-23390-induced increase of the DA and DOPAC levels. The SCH-23390+SKF-38393 and the SCH-23390-only groups showed an increase in the DOPAC/DA ratio. The co-administration of SCH-23390+PARGYLINE significantly decreased the DOPAC levels and the DOPAC/DA ratio compared with the control and SCH-23390 groups. Taken together, our results showed that selective inhibition with SCH-23390 produced an increase in metabolized DA via striatal monoamine oxidase. These findings also contribute to the understanding of the role of postsynaptic D(1) receptors in the long-loop negative feedback system in the rat striatum.

[Paradigm of negative feedback via long-loop in the striatal dopamine release modulation in the rat]. / Paradigma de retroalimentacion negativa via circuito largo en la modulacion de la liberacion de dopamina en el estriado dorsal de la rata.

INTRODUCTION: The basal ganglia include the striatum, globus pallidus, the substantia nigra pars compacta and pars reticulata. The striatum receives afferent input from the substantia nigra pars compacta. The principal neurons of the striatum are medium spiny neurons, that express high levels of D1 and D2 receptors. AIMS: This review deals about the aspects underlying to the negative feedback via long-loop in the striatal dopamine release modulation in the rat. Also, the motor function in dopamine receptor knock-out mice is discussed. DEVELOPMENT AND CONCLUSIONS: The intrastriatal infusion and systemic injection of dopamine receptor agonists and antagonists may regulate the striatal dopamine release and induce changes in motor function. Disruption of the D1 and D2 gene shown that the motor function is controlled by D1 and D2 receptors. The study of the long-loop negative feedback may contribute to our understanding in the physiology and dysfunction of basal ganglia.

Paradigma de retroalimentación negativa vía circuito largo en la modulación de la liberación de dopamina en el estriado dorsal de la rata / Paradigm of negative feedback via long-loop in the striatal dopamine release modulation in the rat

Introducción. El estriado, el globo pálido, la sustancia negra pars compacta y la sustancia negra pars reticulata integran los ganglios basales. El estriado recibe aferencias provenientes de la sustancia negra pars compacta. Las neuronas principales del estriado son las neuronas espinosas de tamaño mediano, que expresan altos niveles de receptores pertenecientes a la familia D1 (RD1) y D2 (RD2). Objetivos. Revisar el paradigma de retroalimentación negativa vía circuito largo en la modulación de la liberación de dopamina en el estriado dorsal de la rata. Además, se discute el efecto de la función motora en ratones deficientes (knockout) de receptores dopaminérgicos. Desarrollo y conclusiones. La infusión local y la inyección sistémica de fármacos agonistas y antagonistas dopaminérgicos modulan la liberación de dopamina estriatal e inducen cambios en la función motora. En ratones deficientes de RD1 o RD2 se ha demostrado que la función motora es dependiente de la integridad del sistema dopaminérgico. El estudio del paradigma de retroalimentación negativa vía circuito largo en la modulación de la liberación de dopamina permitirá comprender el funcionamiento del circuito de los ganglios basales en condiciones fisiológicas y patológicas (AU)

Introduction. The basal ganglia include the striatum, globus pallidus, the substantia nigra pars compacta and pars reticulata. The striatum receives afferent input from the substantia nigra pars compacta. The principal neurons of the striatum are medium spiny neurons, that express high levels of D1 and D2 receptors. Aims. This review deals about the aspects underlying to the negative feedback via long-loop in the striatal dopamine release modulation in the rat. Also, the motor function in dopamine receptor knock-out mice is discussed. Development and conclusions. The intrastriatal infusion and systemic injection of dopamine receptor agonists and antagonists may regulate the striatal dopamine release and induce changes in motor function. Disruption of the D1 and D2 gene shown that the motor function is controled by D1 and D2 receptors. The study of the long-loop negative feedback may contribute to our understanding in the physiology and dysfunction of basal ganglia (AU)