Incidencia, mortalidad y supervivencia al cáncer de próstata en Cali, Colombia, 1962-2011 / Prostate cancer in Cali, Colombia, 1962-2011: incidence, mortality and survival

Objetivo. Analizar la tendencia de las tasas de incidencia, mortalidad y supervivencia al cáncer de próstata (CP) en el periodo 1962-2011. Material y métodos. Con base en el Registro Poblacional de Cáncer en Cali (Colombia) y los registros de mortalidad de la Secretaría de Salud Pública Municipal se analizaron las tendencias de las tasas de incidencia, mortalidad y supervivencia por CP en Cali durante el periodo 1962-2011. Resultados. La incidencia de cáncer de próstata aumentó vertiginosamente entre 1986 y 2002 (Annual Percent Change APC 6.2%) y se estabilizó posteriormente. La mortalidad disminuyó desde 1997 en los mayores de 70 años, mientras que en el grupo de 50-69 años fue a partir de 1981. La supervivencia relativa a cinco años fue 69.8% (IC95% 67.5-72.0) y se asoció de manera significativa con la edad, periodo de diagnóstico y estrato socioeconómico. Conclusión. El incremento en la incidencia del CP coincide temporalmente con la implementación del antígeno específico de próstata (PSA por sus siglas en inglés) en Cali; hay evidencia de mejoría en la supervivencia en el CP y disminución en su mortalidad.

Objective. To analyze the trend in prostate cancer survival, incidence and mortality rates in Cali, Colombia from 1962 to 2011. Materials and methods. Based on the Cancer Registry of Cali, Colombia and the mortality registry of the City's Public Health Secretary, incidence, mortality age-standardized rates and relative survival were calculated during 1962-2011. Results. Prostate cancer incidence rates increased sharply between 1986 and 2002 (APC: 6.21%) and then leveled off. Mortality diminished in 1997 in men older than 70 years-old while in men aged 50-69 years declined since 1981. The 5-year-relative-survival was 69.8% (CI95% 67.5-72.0) and it was significantly associated with age, quinquennial period of diagnosis and socioeconomic strata. Conclusion. The increase in incidence rates of prostate cancer in time coincides with the implementation of the PSA in Cali. There is evidence of improvement in prostate cancer survival, and decreased prostate cancer mortality.

Incidencia, mortalidad y supervivencia por cáncer colorrectal en Cali, Colombia, 1962-2012 / Colorectal cancer incidence, mortality and survival in Cali, Colombia, 1962-2012

Objetivo. Estudiar el comportamiento del cáncer colorrectal (CCR) en Cali, Colombia, durante el periodo 1962-2012, utilizando la información del Registro Poblacional de Cáncer de Cali y de la Secretaría de Salud Municipal de Cali. Material y métodos. Análisis ecológico de series de tiempo para estudiar la tendencia de las tasas de incidencia (1962-2007) y mortalidad por CCR (1984-2012); y un análisis de supervivencia de la serie de casos de CCR registrados en Cali entre 1995-2004. La tendencia temporal de las tasas de incidencia (TIEE) y mortalidad (TMEE) estandarizadas por edad se estudió mediante el cambio medio anual (APC por sus siglas en inglés). Se estimó la supervivencia relativa a cinco años y se hizo un análisis múltiple mediante el modelo de regresión de riesgos proporcionales de Cox. Resultados. Durante el periodo 1962-2007, las TIEE de CCR aumentaron en los hombres y mujeres residentes en Cali; APC= 2.6 (IC95% 2.2-3.0) y APC= 2.2% (IC95% 1.8-2.7), respectivamente. Entre 1984-2012 las TMEE permanecieron estables en las mujeres y en los hombres aumentaron en todos los grupos de edad; APC=1.8 (IC95% 0.8-2.8). La supervivencia relativa a cinco años fue independiente del sexo y aumentó de 29.7% en 1995-1999 a 39.8% durante 2000-2004. El riesgo de morir por CCR fue mayor en las personas de estratos socioeconómicos (ESE) bajos frente a los ESE altos, HR= 2.1 (IC95% 1.7-2.6); en los mayores de 70 años frente a los <50, HR= 2.4 (IC95% 1.9-2.9) y en el periodo 1995-1999 frente al 2000-2004 HR=1.5 (IC95% 1.3-1.7). Conclusión. El cáncer de colon y recto está ocupando un lugar preponderante entre los cánceres de mayor importancia en Cali, Colombia.

Objective. To study the colorectal cancer (CRC) behavior in Cali, Colombia, during the 1963-2012 period using data from the Population-based Cancer Registry of Cali and the Municipal Health Secretariat of Cali. Materials and methods. An ecological time series analysis to study the CRC incidence (1962-2007) and mortality (1984-2012) rate trends; and a survival analysis of CRC cases registered in Cali between 1995 and 2004 were conducted. The age-standardized temporal trend of incidence (I-ASR) and mortality (M-ASR) rates were studied using an annual percent change (APC). The 5-year relative survival was estimated and a multivariate analysis was performed using the Cox proportional hazard regression model. Results. During the 1962-2007 period, CRC TTIR increased in men and women living in Cali [APC= 2.6 (95% CI 2.2-3.0) and APC= 2.2% (95% CI 1.8-2.7), respectively]. In the 1984-2012 period, the TTMR remained stable in women but increased in men in all age groups [APC= 1.8 (95% CI 0.8-2.8)]. The 5-year relative survival was independent of sex and increased from 29.7% in 1995-1999 to 39.8% in 2000-2004. The risk of dying from CRC was higher in people of lower socio-economic status (SES) vs higher SES [HR= 2.1 (95% CI: 1.7-2.6)], among people older than 70 years of age vs younger than 50 years [HR= 2.4 (95% CI: 1.9-2.9)], and for the 1995-1999 period vs 2000-2004 period [HR= 1.5 (95% CI 1.3-1.7)]. Conclusion. CRC is beginning to take a prominent place among the most important cancers in Cali, Colombia.

Expression profile of microrna-145 in urothelial bladder cancer

Purpose Bladder cancer (BC) is the second most common malignancy of the urinary tract, with high mortality. The knowledge of the molecular pathways associated with BC carcinogenesis is crucial to identify new diagnostic and prognostic biomarkers. MicroRNAs (miRNAs) are short non-coding RNA molecules that play important roles in the regulation of gene expression by acting directly on mRNAs. miR-145 has been considered as a tumor suppressor, which targets the c-MYC, MUC-1 and FSCN1 genes. Our aim was to evaluate the expression profile of miR-145 in low-grade non-invasive and high-grade invasive bladder urothelial carcinomas. Materials and Methods We studied 30 specimens of low-grade, non-invasive pTa and 30 of pT2/pT3 high-grade invasive UC obtained by transurethral resection or radical cystectomy, followed over a mean time of 16.1 months. Normal controls were represented by five samples of normal bladder biopsy from patients who underwent retropubic prostatectomy to treat BPH. miRNA extraction and cDNA generation were performed using commercial kits. Analysis was performed by qRT-PCR, and miR-145 expression was calculated using the 2-∆∆ct method; we used RNU-43 and RNU-48 as endogenous controls. Results miR-145 was under-expressed in 73.3% and 86.7% of pTa and pT2/pT3, respectively, with expression means of 1.61 for the former and 0.66 for the last. There were no significant differences in miR-145 expression and histological grade, tumor stage, angiolymphatic neoplastic invasion and tumor recurrence. Conclusion miR-145 is under-expressed in low-grade, non-invasive and high-grade invasive urothelial bladder carcinoma and may play an important role in the carcinogenesis pathway, being an interesting candidate diagnostic marker. .

Tgf-β1 expression as a biomarker of poor prognosis in prostate cancer

OBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of li patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-β1 was underexpressed 67.0 percent of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores >7 when compared to patients with Gleason scores <7(p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3 percent had poor prognostic features. CONCLUSIONS: TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.

Effects of Excretory/Secretory Products from Clonorchis sinensis and the Carcinogen Dimethylnitrosamine on the Proliferation and Cell Cycle Modulation of Human Epithelial HEK293T Cells

Clonorchis sinensis is one of the most prevalent parasitic helminths in Korea. Although cholangiocarcinoma can be induced by C. sinensis infection, the underlying mechanism is not clearly understood. To assess the role of C. sinensis infection in carcinogenesis, an in vitro system was established using the human epithelial cell line HEK293T. In cells exposed to the excretory/secretory products (ESP) of C. sinensis and the carcinogen dimethylnitrosamine (DMN), cellular proliferation and the proportion of cells in the G2/M phase increased. Moreover, the expression of the cell cycle proteins E2F1, p-pRb, and cyclin B was dramatically increased when ESP and DMN were added together. Similarly, the transcription factor E2F1 showed its highest level of activity when ESP and DMN were added simultaneously. These findings indicate that DMN and ESP synergistically affect the regulation of cell cycle-related proteins. Our results suggest that exposure to C. sinensis and a small amount of a carcinogen such as DMN can promote carcinogenesis in the bile duct epithelium via uncontrolled cellular proliferation and the upregulation of cell cycle-related proteins.

An alternatively spliced form of Met receptor is tumorigenic

The Met tyrosine kinase receptor is a widely expressed molecule, which mediates pleiotropic cellular responses following activation by its ligand, hepatocyte growth factor/scatter factor (HGF/SF). Previously, one of the authors identified an alternatively spliced form of Met (Met-SM) that lacked a single exon of a 47-amino-acid segment in the juxtamembrane domain. Here we report that Met-SM is a potent transforming gene in NIH3T3 mouse fibroblast cells. Met-SM-transfected NIH3T3 cells show stronger foci-forming activity than wild type-Met-transfected ones. In addition, Met-SM-transfected NIH3T3 cells form colonies in soft agar and are tumorigenic in athymic nu/nu mice. Furthermore, HGF/SF significantly increases the focus-forming activity of Met-SM comparing to wild type Met. The amount of protein and of tyrosine kinase activity of Met-SM accumulates to a high level following HGF/SF treatment. The accumulation of Met-SM correlated well with its delayed ubiquitination and increased stability. These results are consistent with the important role of the juxtamembrane domain in protein stability of Met receptor and suggest that the alternatively-spliced form may contribute to the development and progression of human cancer.

Modulatory influence of Brassica compestris Linn var sarson on phase-II carcinogen metabolizing enzymes and glutathione levels in mice.

The present study reports the modulatory influence of 95% ethanolic extract from the seeds of B. compestris on the activity of phase-II enzymes such as glutathione S-transferase (GST), DT-diaphorase (DTD) and reduced glutathione (GSH) level in the skin, lung, kidney and forestomach of the mouse. Oral treatment with the seed extract at 800 mg/kg body wt. for 15 days significantly elevated GST in lung and forestomach and DT-diaphorase in forestomach and skin and GSH level in lung, kidney forestomach and skin. The lower dose 400 mg/kg body wt was effective only in inducing GST and DT-diaphorase activity in forestomach and reduced glutathione level in lung. The findings suggest that B. compestris seed extract may block or suppress the events associated with chemical carcinogenesis at least in part, by inducing metabolic detoxification of the carcinogen.

El colesterol es esencial en el desarrollo embrionario y en el crecimiento celular / Cholesterol as an essential factor for embryonic and cellular growth

El colesterol es indispensable para el desarrollo y crecimiento celular. En varios organismos, como en los insectos, el colesterol se considera una vitamina, ya que debe ser ingerido en los alimentos. En Drosophila, el colesterol es esencial para la embriogénesis y en su ausencia estas moscas no desarrollan las alas. Esto se debe a la interacción entre el colesterol y las proteínas hedgehog. También es necesaria la presencia de colesterol en la regulación de varias enzimas, sobre todo en las que están en relación con su síntesis. Finalmente, se ha observado que algunos intermediarios de la síntesis del colesterol modulan la velocidad del ciclo celular al interactuar con el DNA nuclear y, al parecer, esta asociación también está relacionada con los procesos cancerígenos.

Reduced toxicity and enhanced antitumor efficacy of betacyclodextrin plumbagin inclusion complex in mice bearing Ehrlich ascites carcinoma.

Inclusion complex of plumbagin was prepared with betacyclodextrin employing neutralization method. The toxicity of the drug was reduced and the antitumor efficacy was enhanced on complexation with betacyclodextrin.

Tumor promoter-like activity of the molluscicidal latex of 'Crown-of-Thorns' (Euphorbia milii var. hislopii) in the V79 metabolic cooperation assay

The latex of 'Crown-of-Thoms'(Euphorbia miliivar. hislopii, syn. E. splendens) has been shown to be a potent plant molluscicide that could be used against the snails which are intermediate hosts of Schistosoma trematodes. However, a comprehensive toxicological evaluation of the latex is necessary before its large-scale use in schistosomiasis control becomes possible. In fact, one cause for concern is the presence of tumor-promoting phorbol esters in several plants of the Euphorbiaceae family. Phorbol esters as well as a number of other known tumor promoters share the common property of inhibiting metabolic cooperation (i.e., exchange of low molecular weight molecules via gap junctions) between Chinese hamster V79 cells in monolayer cultures. The present study was undertaken to determine if latex of E. milii presents tumor promoter-like activity in this shortterm in vitro assay. Samples of lyophilized E. milii latex were tested at a noncytotoxic concentration range (1, 10, 50 and 100 mug/ml) in three independent experiments. 12-0-Tetradecanoylphorbol-13-acetate (10 ng/ml) was used as positive control. In all three assays, E. milii latex consistently inhibited metabolic cooperation between V79 cells at concentrations (10 mug/ml. These results indicate that E. milii latex contains tumor-promoting substances. These findings suggest that the use of crude latex as a molluscicide may pose a carcinogenic hazard to people who are continuously exposed to the product.

Malignant transformation by hydrazine derivatives: a role for carbon-centered radicals?

There are several hydrazine derivatives with pharmacological activity, all of which have carcinogenic properties in experimental animals. Several mono- and disubstituted derivatives have been shown to produce carbon-centered radicals upon oxidation by enzymatic systems such as HbO2' Cytochrome P-450, monoamine oxidases, horseradish peroxidase and myeloperoxidase. Proposed mechanisms of hydrazine metabolism leading to alkylating species are discussed. The in vitro induction of DNA alterations by carbon-centered radicals generated in hydrazine metabolism ascertains the possibility of its occurrence in vivo. Our results, discussed herein, established the induction of cytotoxicity, proliferation and transformation of cultured mouse fibroblasts by systems in which hydrazine-derived alkyl radicals are formed. These studies represent another step towards distinguishing the possible involvement of metabolism-generated carbon-centered radicals in the onset of carcinogenic processes, which reinforces the importance of additional experimental approaches in order to consolidate this hypothesis.

Câncer do pulmäo: carcinogênese, histogênese e biomarcadores / Lung cancer: carcinogenesis, histogenesis and biological markers

Tecem-se consideraçöes sobre a induçäo de tumores malignos ao nível da mucosa bronquial, provocada especialmente por compostos químicos pro-carcinogênicos e que necessitam de ativaçäo metabólica antes de se unirem a macromoléculas (DNA, RNA, Proteínas). Em seguida comenta a histogênese destas neoplasias a partir de células basais ativadas ou células glandulares mucosas. Os biomarcadores associados aos tumores malignos broncogênicos têm merecido uma especial atençäo dos estudiosos do assunto. A sua utilizaçäo como monitores do curso clínico de tumores pulmonares previamente diagnosticados e como adjuvantes no diagnóstico diferencial merecem especial destaque na medicina contemporânea. Descrevem-se os biomarcadores detectados no soro bem como destaca o valor da imunocitoquímica na avaliaçäo de alguns destes marcadores em espécimens fixados em formol e embebidos na parafina