Survivin drives tumor-associated macrophage reprogramming: a novel mechanism with potential impact for obesity.

PURPOSE: Recent studies point to adipose-derived stem cells (ASCs) as a link between obesity and cancer. We aimed to determine whether survivin, which is highly secreted by ASCs from subjects with obesity, might drive a pro-tumoral phenotype in macrophages. METHODS: The effect of ASC conditioned medium on the macrophage phenotype was assessed by expression studies. Survivin intracellular localization and internalization were examined by subcellular fractionation and immunofluorescence, respectively. Loss- and gain-of-function studies were performed using adenoviral vectors, and gene expression patterns, migration and invasion capacities of cancer cells were examined. Heterotypic cultures of ASCs, macrophages and cancer cells were established to mimic the tumor microenvironment. Survivin-blocking experiments were used to determine the impact of survivin on both macrophages and cancer cells. Immunohistochemical analysis of survivin was performed in macrophages from ascitic fluids of cancer patients and healthy controls. RESULTS: We found that obese-derived ASCs induced a phenotypic switch in macrophages characterized by the expression of both pro- and anti-inflammatory markers. Macrophages were found to internalize extracellular survivin, generating hybrid macrophages with a tumor-associated phenotype that included secretion of survivin. Exogenous expression of survivin in macrophages generated a similar phenotype and enhanced the malignant characteristics of cancer cells by a mechanism dependent on survivin phosphorylation at threonine 34. Survivin secreted by both ASCs from subjects with obesity and tumor-associated macrophages synergistically boosted the malignancy of cancer cells. Importantly, survivin was mainly detected in ascites-associated macrophages from patients with a malignant diagnosis. CONCLUSION: Our data indicate that survivin may serve as a molecular link between obesity and cancer and as a novel marker for tumor-associated macrophages.

[Diagnostic validity of Zung's self-rating depression scale on primary care patients]. / Validez diagnóstica de la Self-Rating Depression Scale de Zung en pacientes de atención primaria.

INTRODUCTION: Although the Spanish version of the Zung's Self-Rating Depression Scale (SDS) is widely used, there are no studies about its validity as a diagnostic test in primary health care patients. METHODS: In a first phase, a sample of 350 consecutive primary care patients was assessed with the SDS. In a second phase, a subsample composed by all the positive test results and 1/3 of the negatives selected at random, was assessed with the modules of current Major Depressive Episode and Dysthymia of the Structured Clinical Interview for DSM-IV. Specific methods to avoid verification bias were used. Prevalence, sensitivity and specificity, predictive values, Receiver Operating Characteristic (ROC) curve, and Stratum Specific Likelihood Ratios (SSLR) were calculated. RESULTS: Prevalence estimations of major depression and dysthymia were 14,7% (IC95%: 10,7-18,7%) and 4,6% (IC95%: 2,4%-6,8%) respectively. Sensitivity and specificity to detect both diagnoses were 0,95 (IC95%: 0.87-1) and 0,74 (IC95%: 0,68-0,79). Area under ROC curve was 0,93. SSLR for scoring < 50 led to a post-test probability of 0.01. In the stratum with scoring > 69 the SSLR generated a post-test probability of 0.96. Less conclusive results were obtained by intermediate strata. CONCLUSIONS: The SDS is effective in primary care patients and shows operating characteristics comparable to other depression assessment scales. SSLR provides practical information to estimate the probability of suffer a depressive disorder in individual patients.

[Prevalence and characteristics of major depression and dysthymia in primary care]. / Prevalencia y características de la depresión mayor y la distimia en atención primaria.

OBJECTIVE: To find the prevalence and characteristics of depressive disorders in patients consulting in primary care.Design. Cross-sectional descriptive study. Two stages: screening, then structured psychiatric interview.Setting. Eight clinics at four primary care centres. PATIENTS AND METHODS: A sample of 350 consecutive patients aged between 18 and 70 filled out Zung's Self-Rating Depression Scale (SDS). The diagnoses of major depressive episode and dysthymia for the 138 with positive result and the 67 with negative result were investigated through the Structured Clinical Interview for DSM-IV Axis I Disorders. Measurements and main results. We found a weighted prevalence of 14.7% (95% CI: 10.7-18.7) for major depression and 4.6% (95% CI: 2.4-6.8) for dysthymia. Mean score on the SDS was 65.6 (SD 11.6) in the group with major depression and 63.3 (SD 8.7) in the group with dysthymia. Mean score in the not-depressed group was 44.2 (SD 8.7), lower than the scores for both groups with depression (p < 0.0001). Being female distinguished the depressed groups from the not-depressed group. Lower educational level and the amount of over-users distinguished the group with major depression from the not-depressed group. The symptom profiles were virtually identical for the two depressed groups, whereas the frequency of occurrence of most of the symptoms explored differed significantly between those with and without depression. CONCLUSIONS: Prevalence of major depression and dysthymia are high in primary care patients in our area. Both disorders have common characteristics of demographic variables and symptom profile.

[Prevalence, expression and impact of depressive disorders in primary care]. / Prevalencia, expresión e impacto de los trastornos depresivos en atención primaria.

OBJECTIVE: To determine the prevalence and forms of clinical expression of depressive disorders in primary care patients. To analyse the under-detection of depression by primary care doctors. DESIGN: Descriptive and transversal study, with two-stage sampling. Setting. Primary care consultations in the Camp de Tarragona area. PARTICIPANTS: 1000 consecutive patients visiting their doctor for any reason will make up the first-stage sample. Of these 350 go on to the second stage (all the positive results in the screening for depression test plus a random one-seventh of the negative results). MAIN MEASUREMENTS: The first stage will consist of the screening of the sample for depressive disorders with Zung's Self-Rating Depression Scale. In the sub-sample that will go on to the second stage, the Structured Clinical Interview for DSM-IV Disorders will be used to establish diagnoses of depressive disorders and other co-morbid psychiatric disorders. There will also be a range of specific questionnaires to find reasons for consultation and the form of presentation of an eventual depressive disorder, medical co-morbidity, medication taken, use of health services, the functional and vital repercussions of depression. A questionnaire for the patient's G.P. will assess and detect depression. DISCUSSION: The study will enable us to check the validity for our patients of pre-suppositions on depression in primary care obtained from studies in other countries with different health structures and social and cultural conditioners, and to find diverse information extrapolated from specialist studies.

[An evaluation of the Reflotron portable analyzer for cholesterol determination in primary care]. / Evaluación de un analizador portátil, reflotron, para la determinación del colesterol en atención primaria.

We have evaluated serum cholesterol in a primary care center with a recently introduced portable analyzer: Reflotron (Boehringer Mannheim). The linearity and exactitude were investigated with Hitachi 704 (Boehringer Mannheim) used in the reference laboratory. Accuracy was also tested. We found a good accuracy after repeated analysis (n = 30) of two control sera with a variation coefficient of 2.77% in the first (mean = 125.14 mg/dl, SD 3.47) and 2.94% (mean = 254.53 mg/dl, SD 7.49) in the second. We found an overall lack of accuracy of Reflotron with a more pronounced negative bias in capillary blood (mean d = 30.93 mg/dl, dSE 3.25) than in serum (mean d = dSE 1.12). We found a positive linear correlation both using serum (r = 0.9845; n = 45) and capillary blood (r = 0.9094; n = 30). We feel that Reflotron is useful for primary care due to its good accuracy and linearity regarding the reference method, but its inexactitud should be taken into account. We emphasize the need for quality control to investigate its limitations when the results are analyzed.