Estudio preliminar sobre la evaluación del dolor mecánico a la presión y los mecanismos de modulación central del dolor mediante algometría en una unidad de anestesia / Preliminary study on the evaluation of mechanical pressure pain and central pain modulation mechanisms by algometry in an anesthesia unit

Introducción: La algometría de presión es un método válido para evaluar el sistema sensorial de transmisión del dolor en seres humanos, mediante pruebas como la sumación temporal y la modulación condicionada del dolor. El objetivo de este trabajo fue la realización de una experiencia preliminar en el Servicio de Anestesio­logía de nuestro Hospital Universitario, utilizando la algometría de presión como test sensorial cuantitativo. Metodología: En una primera etapa, se realizó un estudio transversal de caso y control, sin aleatorización, donde se midió el umbral de dolor a la presión por algometría de presión a 58 pacientes que consultaron en la policlínica preoperatoria. Dieciocho tenían algún tipo de dolor crónico (grupo con dolor) y 40 no tenían dolor (grupo sin dolor). En una segunda etapa, se realizó un estudio observacional a 36 voluntarios sanos, residentes de anestesiología. En 16 se estudió la sumación temporal y en 20 la modulación condicionada del dolor, en ambos casos utilizando la algometría de presión. La aplicación de presión con manguito en el brazo se utilizó como estímulo heterotópico. Ambas pruebas fueron medidas a nivel del músculo trapecio derecho. Resultados: En el grupo con dolor el valor del umbral de dolor a la presión fue menor que en el grupo sin dolor en todos los puntos evaluados. El valor del umbral de dolor a la presión promedio de las cuatro regiones analizadas en el grupo con dolor, resultó ser menor que en el grupo sin dolor, 32,7 ± 10 Newtons versus 42 ± 11,7 Newtons (p = 0,004). El umbral de dolor a la presión promedio resultó más bajo en pacientes de sexo femenino que en los de sexo masculino, 36,6 ± 9 Newtons versus 48 ± 11 Newtons (p = 0,001)...(AU)

Introduction: Pressure algometry is a valid method to evaluate the sensory system of pain transmission in humans, using tests such as temporal summation and conditioned modulation of pain. The objective of this work was to carry out a preliminary experience in the Anesthesiology Service of our University Hospital, using pressure algometry as a quantitative sensory test. Methodology: In a first stage, a cross-sectional case-control study was carried out, without randomization, where the pressure pain threshold was measured by pressure algometry in 58 patients who consulted in the preoperative evaluation visit. Eighteen had some type of chronic pain (pain group) and 40 had no pain (pain-free group). In a second stage, an observational study was carried out on 36 healthy volunteers, anesthesiology residents. Temporal summation was studied in 16 and conditioned modulation of pain in 20, in both cases using pressure algometry. The application of cuff pressure to the arm was used as a heterotopic stimulus. Both tests were measured at the level of the right trapezius muscle. Results: In the group with pain, the pressure pain threshold value was lower than in the group without pain in all the points evaluated. The pain threshold va­lue at the mean pressure of the four regions analyzed in the group with pain, turned out to be lower than in the group without pain, 32.7 ± 10 Newtons versus 42 ± 11.7 Newtons (p = 0.004). The mean pressu­re pain threshold was lower in female patients than in male patients, 36.6 ± 9 Newtons versus 48 ± 11 Newtons (p = 0.001). In the 20 healthy volunteers who underwent the conditioned modulation of pain test at the trapezius level, the pain threshold at the initial pressu­re was 63 ± 27 Newtons and the final pressure was 72 ± 28 Newtons, with an average increase of 9 Newtons (14.2 %)...(AU)

Las inyecciones epidurales lumbares de esteroides reducen el catastrofismo en el síndrome radicular lumbosacro / Lumbar epidural steroids injections reduce catastrophism on the lumbosacral radicular syndrome

Objetivo: Estudiar la influencia del catastrofismo sobre el dolor lumbar crónico radicular y evaluar sus cambios a la inyección epidural de esteroides. Además, estudiar la relación entre catastrofismo y la respuesta al tratamiento. Material y métodos: Se realizó un estudio prospectivo sobre 52 pacientes con lumbociatálgia crónica unilateral, a los que se le realizó una inyección epidural lumbar de esteroides. En 39 de ellos se valoró en condiciones basales y al mes del procedimiento, el dolor y el catastrofismo mediante el Inventario Abreviado de Dolor y la Escala de Catastrofismo. Se definó como "respon­dedores" a los pacientes con disminución de 2 puntos o más en la intensidad del dolor. Para el catastrofismo se consideró un score de 30 como severo. Un valor de p < 0,05 se consideró de significancia estadística. Resultados: El catastrofismo total fue mayor en mujeres que en hombres. Se encontró una correlación lineal positiva moderada entre catastrofismo, intensidad del dolor e índice de interferencia, estadísticamente significativa. En los 39 pacientes tratados, se encontró una disminución estadísticamente significativa de la intensidad, interferencia funcional del dolor y catastrofismo total. Dieciseis pacientes se considera­ron respondedores. En estos, el índice de intensidad disminuyó de 7,8 ± 0,8 a 3,9 ± 3,1 (50 % de porcentaje de cambio, p = 0,0001); la interferencia funcional del dolor evaluada por el índice de interferencia disminuyó de 8,2 ± 1,6 a 5,0 ± 3,8 (40 % de cambio, p = 0,0027) y el catastrofismo total disminuyó de 37 ± 13 a 17,5 ± 16 (57 % de cambio, p < 0,0001). El catastrofismo total previo no mostró diferencias entre los pacientes respondedores y no respondedores a las inyecciones epidurales de esteroides. Conclusiones: La inyección epidural de esteroides en pacientes con dolor lumbar radicular crónico resultó efectiva para disminuir el dolor y sus repercusiones funcionales...(AU)

Objetive: The aim of this study was to investigate the relationship existent between pain catastrophism and pain intensity and pain interference, in patients with lumbosacral radicular pain. The effect on catastrophism of epidural steroid injections was also asessed. Material an methods: A prospective study was conducted on 52 patients with unilateral lumbosacral radi­cular pain. In 39 of them, the Brief Pain Inventory and the Catastrophism Scale was applied before and one month afer a epidural steroid injection. Responderes to treatment ere defined with a decrease of 2 points or more in pain intensity. For catastrophism, a score of 30 was considered severe. A value of p < 0.05 was taken as statistical significance. Results: Catastrophism was significantly higher in women. Moderate and statistically significant positive linear correlations between pain intensity, pain interference and catastrophism were found. In treated patients, a significant decrease in pain intensity, pain interference and catastrophism were observed. Sixteen patients were considered treatment responders. In them, pain intensity and catastrophism had a clinical and statistically significant reduction. Score of Intensity was reduced from 7.8 ± 0.8 to 3.9 ± 3.1 (50 % of change percentage, p = 0.0001), functional interfe­rence of pain evaluated by Score of Interference from 8.2 ± 1.6 to 5.0 ± 3.8 (40 % of change percentage, p = 0.0027) and Total Catastrophism from 37 ± 13 to 17.5 ± 16 (57 % of change percentage, p < 0.0001). No difference were found in Total Catastrophism evaluated before the proceduresl between responders and no responders to epidural steroid injections. Conclusions: Epidural steroid injections was effective in reducing pain in 41 % of controlled patients. The decrease in pain was accompanied by a reduction in Total Catastrophism, which showed to be a dynamic cons­truct, capable of being modified by interventional pain treatments...(AU)

Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Inhibition of the spindle assembly checkpoint kinase Mps-1 as a novel therapeutic strategy in malignant mesothelioma.

Malignant mesothelioma (MM) is an aggressive malignancy, highly resistant to current medical and surgical therapies, whose tumor cells characteristically show a high level of aneuploidy and genomic instability. We tested our hypothesis that targeting chromosomal instability in MM would improve response to therapy. Thr/Tyr kinase (TTK)/monopolar spindle 1 kinase (Mps-1) is a kinase of the spindle assembly checkpoint that controls cell division and cell fate. CFI-402257 is a novel, selective inhibitor of Mps-1 with antineoplastic activity. We found that CFI-402257 suppresses MM growth. We found that Mps-1 is overexpressed in MM and that its expression correlates with poor patients' outcome. In vitro, CFI-402257-mediated inhibition of Mps-1 resulted in abrogation of the mitotic checkpoint, premature progression through mitosis, marked aneuploidy and mitotic catastrophe. In vivo, CFI-402257 reduced MM growth in an orthotopic, syngeneic model, when used as a single agent, and more so when used in combination with cisplatin+pemetrexed, the current standard of care. Our preclinical findings indicate that CFI-402257 is a promising novel therapeutic agent to improve the efficacy of the current chemotherapeutic regimens for MM patients.

Minimal asbestos exposure in germline BAP1 heterozygous mice is associated with deregulated inflammatory response and increased risk of mesothelioma.

Germline BAP1 mutations predispose to several cancers, in particular malignant mesothelioma. Mesothelioma is an aggressive malignancy generally associated with professional exposure to asbestos. However, to date, we found that none of the mesothelioma patients carrying germline BAP1 mutations were professionally exposed to asbestos. We hypothesized that germline BAP1 mutations might influence the asbestos-induced inflammatory response that is linked to asbestos carcinogenesis, thereby increasing the risk of developing mesothelioma after minimal exposure. Using a BAP1(+/-) mouse model, we found that, compared with their wild-type littermates, BAP1(+/-) mice exposed to low-dose asbestos fibers showed significant alterations of the peritoneal inflammatory response, including significantly higher levels of pro-tumorigenic alternatively polarized M2 macrophages, and lower levels of several chemokines and cytokines. Consistent with these data, BAP1(+/-) mice had a significantly higher incidence of mesothelioma after exposure to very low doses of asbestos, doses that rarely induced mesothelioma in wild-type mice. Our findings suggest that minimal exposure to carcinogenic fibers may significantly increase the risk of malignant mesothelioma in genetically predisposed individuals carrying germline BAP1 mutations, possibly via alterations of the inflammatory response.

Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression.

High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information.

In vitro and in vivo anticancer effects of mevalonate pathway modulation on human cancer cells.

BACKGROUND: The increasing usage of statins (the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) has revealed a number of unexpected beneficial effects, including a reduction in cancer risk. METHODS: We investigated the direct anticancer effects of different statins approved for clinical use on human breast and brain cancer cells. We also explored the effects of statins on cancer cells using in silico simulations. RESULTS: In vitro studies showed that cerivastatin, pitavastatin, and fluvastatin were the most potent anti-proliferative, autophagy inducing agents in human cancer cells including stem cell-like primary glioblastoma cell lines. Consistently, pitavastatin was more effective than fluvastatin in inhibiting U87 tumour growth in vivo. Intraperitoneal injection was much better than oral administration in delaying glioblastoma growth. Following statin treatment, tumour cells were rescued by adding mevalonate and geranylgeranyl pyrophosphate. Knockdown of geranylgeranyl pyrophosphate synthetase-1 also induced strong cell autophagy and cell death in vitro and reduced U87 tumour growth in vivo. These data demonstrate that statins main effect is via targeting the mevalonate synthesis pathway in tumour cells. CONCLUSIONS: Our study demonstrates the potent anticancer effects of statins. These safe and well-tolerated drugs need to be further investigated as cancer chemotherapeutics in comprehensive clinical studies.

Picolinic acid- or desferrioxamine-inducible autocrine activation of macrophages engineered to produce IFNgamma: an approach for gene therapy.

Macrophage (Mphi)-based vectors are highly mobile cellular shuttles designed to deliver therapeutic genes within the tissues. We engineered a mouse Mphi cell line to express the murine interferon-gamma (IFNgamma) under the control of an inducible promoter containing the hypoxia-responsive element, which can be triggered by hypoxia and other stimuli. We show that this Mphi vector can be induced to produce IFNgamma under normoxic conditions by stimulation with picolinic acid (PA), a catabolite of tryptophan, or desferrioxamine (DFX), an iron-chelating drug. The Mphi vector responds to IFNgamma with the induction of IRF-1 and of other IFNgamma-inducible genes, the expression of Ia antigens and induction of phagocytic activity. Inducible nitric oxygen synthase gene expression, nitric oxide production, as well as TNFalpha secretion were enhanced by PA or DFX as the sole stimuli. None of the above responses could be triggered individually by PA or DFX in control, normal Mphi, indicating that the Mphi vector overcame the need for costimulatory molecules derived from the immune system for its full activation. Furthermore, we demonstrate that extracellular iron can downregulate such response, thereby identifying an additional tool for the fine tuning of the Mphi vector response to stimulation.

First-line chemotherapy with epidoxorubicin, paclitaxel, and carboplatin for the treatment of advanced epithelial ovarian cancer patients.

OBJECTIVE: A combination of carboplatin (CBDCA) and paclitaxel (TAX) is the standard treatment in advanced ovarian cancer (AOC) patients. Epidoxorubicin (EDX) is an active treatment in AOC and exhibits nonoverlapping toxicities with CBDCA and TAX; moreover, when added to platinum-based chemotherapy, it improves long-term survival. We have therefore conducted a phase II study to evaluate the tolerability and antitumor activity of an EDX/TAX/CBDCA (ETC) triplet in AOC patients. METHODS: Patients with histologically confirmed suboptimal stage III-IV ovarian cancer who had not previously received cytotoxic drugs were treated with TAX (175 mg/m(2) in a 3-h iv infusion), CBDCA (AUC 6, Calvert formula), and EDX (75 mg/m(2) iv bolus) all given on day 1 every 28 days for a maximum of six courses on an outpatient basis. EDX dosage was chosen after a pilot phase I study. RESULTS: Fifty-five patients were registered, of whom 5 were determined ineligible bacause of age. Forty-two of the 50 are evaluable for response; 27 (64%) achieved a clinical complete response (CR) and 9 (21%) a partial response (PR) for a response rate of 86% (95% CI 71-94%). Thirty-three patients underwent a secondary debulking procedure after a median of 6 courses (range 2-6). Pathological CR and PR were observed in 9 (27.3%) and 21 (63.6%), respectively; among patients with persistent disease a successful cytoreduction (<1 cm) was obtained in 53.8% of patients. At a median follow up of 35.6 months (range 0-55.5) median progression-free survival is 19.5 months and median overall survival is 36 months. The most common adverse effects were G3-4 leukopenia and thrombocytopenia which occurred in 59 and 37% of patients, respectively. CONCLUSIONS: The ETC combination given according to the outlined doses and schedule is highly active in AOC patients with poor prognostic factors and deserves further study.

Engineering of macrophages to produce IFN-gamma in response to hypoxia.

Activation of murine macrophages (Mphi) requires the collaboration of signals derived from the immune system and the environment. In this study, we engineered a murine Mphi cell line to become activated in response to an environmental signal, hypoxia, as the sole stimulus. Hypoxia is a condition of low oxygen tension, occurring in several pathological tissues, which acts in synergy with IFN-gamma to induce full Mphi activation. We transfected the ANA-1 murine Mphi cell line with a construct containing the IFN-gamma gene controlled by a synthetic promoter inducible by hypoxia (HRE3x-Tk), and we characterized the cellular and molecular biology of the engineered Mphi under normoxia or hypoxia. Engineered Mphi in normoxia expressed basal levels of IFN-gamma mRNA and protein that were strongly augmented by shifting the cells to hypoxia. Furthermore, they responded to the synthesized IFN-gamma with induction of IFN-responsive factor-1 and 2'-5'-oligoadenylate synthase expression. Under normoxic conditions, the engineered Mphi had a significant constitutive level of Ia Ags and Fc receptors. Hypoxia induced further augmentation of Ia and Fc expression. Finally, hypoxia induced inducible NO synthase expression, and subsequent reoxygenation led to the production of NO. In conclusion, the engineered Mphi, which produce IFN-gamma in an inducible manner, express new biochemical and functional properties in response to low oxygen environment as the sole stimulus, thereby circumventing the need for costimulation by other immune system-derived signals.

Generation of high-titer retroviral vector-producing macrophages as vehicles for in vivo gene transfer.

The goal of this project was to develop a novel gene transfer system based on macrophages (Mphi) as shuttles of recombinant retroviral vectors carrying therapeutic or marker genes. The murine Mphi cell line WGL5 was used as a source of Mphi for this study. We generated retrovirus-producing Mphi by transducing the WGL5 cells with a replication-defective retroviral vector carrying the enhanced green fluorescent protein (EGFP) reporter gene and the Moloney murine leukemia virus (MoMLV) as helper virus. We demonstrated stable integration of the recombinant retrovirus in the Mphi genome, efficient recombinant retrovirus production, and EGFP gene delivery to different cell lines in vitro. To evaluate Mphi-mediated EGFP gene transfer in vivo, allogeneic mice were injected s.c. with the retrovirus-producing WGL5 Mphi, that gave rise to solid tumor masses at the injection site, highly infiltrated with host leukocytes. We observed EGFP fluorescence in tumor-infiltrating CD4(+) and CD8(+) host T lymphocytes, providing direct evidence of the ability of engineered Mphi to mediate EGFP gene delivery to host cells in vivo. Moreover, we showed that retrovirus-producing Mphi could home to different organs in vivo following i.v. injection into mice. These data demonstrate that Mphi can be engineered as cellular vehicles for recombinant retroviruses carrying heterologous genes and suggest potential applications of this novel vector system for gene therapy.

The propensity to apoptosis of centrocytes and centroblasts correlates with elevated levels of intracellular myc protein.

In this study, we investigated the c-myc expression by tonsillar germinal center (GC) B cells using reverse transcriptase-polymerase chain reaction, flow cytometry, Western blot and in situ immunohistochemical methods. The results obtained demonstrate elevated levels of c-myc mRNA and of Myc protein in GC B cells compared to those of the other resting or activated tonsillar B cells. Separation of GC B cells into centroblasts and centrocytes revealed that, while differing in their cell cycle status, surface marker expression and morphology, the two cell types had the same propensity to apoptosis and elevated Myc protein expression, thus reinforcing the notion of a close correlation between these two events. Based upon these observations and other considerations it is proposed that elevation of Myc proteins confers to GC B cells a particular propensity to apoptosis, while the subsequent decision between progression into the cell cycle or programmed cell death is dictated by other signals that are delivered in the GC and perhaps operate at the level of other proto-oncogenes.

Effect of adjuvant chemotherapy with or without anthracyclines on the activity and efficacy of first-line cyclophosphamide, epidoxorubicin, and fluorouracil in patients with metastatic breast cancer.

PURPOSE: To evaluate the effect of previous adjuvant chemotherapy with or without anthracyclines on overall survival (OS), progression-free survival (PFS), and objective response (OR) rates of metastatic breast cancer patients treated with cyclophosphamide, epidoxorubicin, and fluorouracil (CEF) as first-line chemotherapy. PATIENTS AND METHODS: Three-hundred twenty-six assessable metastatic breast cancer patients entered onto four consecutive randomized trials performed in our Institution and North-West Oncology Group (GONO) cooperative centers from 1983 to 1994. Patients received CEF-based chemotherapy as first-line therapy and were then evaluated. One hundred forty-four patients (44%) did not receive previous adjuvant chemotherapy, and 143 (44%) and 39 (12%) patients received cyclophosphamide, methotrexate, and fluorouracil (CMF)-based and anthracycline-based adjuvant chemotherapy, respectively. RESULTS: ORs to CEF chemotherapy were observed in 161 patients (49.4%). On univariate analysis, patients who had received prior adjuvant chemotherapy had a significantly lower probability of response than patients who did not: 43% versus 58% (P=.02). No difference between CMF-based (OR rate, 43%) and anthracycline-based (OR rate, 44%) adjuvant chemotherapy was observed. Stepwise logistic regression analysis indicated that adjuvant chemotherapy (P=.005), bone as dominant metastatic site (P=.02), and previous hormonotherapy for metastatic disease (P=.005) were the most important factors in predicting a poor OR rate. The median PFS and OS times of the whole group were 9.8 and 17.9 months, respectively. Patients who did not receive adjuvant chemotherapy had a longer survival time (21.1 months) compared with patients previously treated with CMF-based (15.3 months) or anthracycline-based (15.8 months) adjuvant chemotherapy. Multivariate analysis confirmed adjuvant chemotherapy to be among the strongest prognostic factors associated with both a poor PFS and OS. CONCLUSION: Previous adjuvant chemotherapy adversely affects OR, PFS, and OS in metastatic breast cancer patients treated with the CEF regimen as first-line chemotherapy. No difference was observed between patients previously treated with CMF-based or anthracycline-based adjuvant chemotherapy.

Lactoferrin down-modulates the activity of the granulocyte macrophage colony-stimulating factor promoter in interleukin-1 beta-stimulated cells.

The human neutrophil lactoferrin (Lf), a cationic iron-binding glycoprotein, has an inhibitor role on granulocyte macrophage colony-stimulating factor (GM-CSF) production via interleukin-1 (IL-1). The nuclear localization of Lf suggests that it may be involved in the transcriptional regulation of GM-CSF gene expression. To explore this possibility, the effect of Lf on GM-CSF gene expression was investigated in various cell lines and in primary cultures of fibroblasts. Down-regulation of GM-CSF mRNA level was observed in Lf-transfected embryonic fibroblasts induced to produce GM-CSF by IL-1 beta. In 5637 cell-line and in embryonic fibroblasts, co-transfection experiments, in which an Lf expression vector was used together with a vector carrying a reporter gene linked to the GM-CSF promoter, revealed that Lf reduces the activity of the GM-CSF promoter. This effect is marked in IL-1 beta-stimulated cells. These findings suggest that Lf plays a negative role in GM-CSF expression at the transcriptional level, perhaps through the mediation of IL-1 beta.

[Intraoperative cyto-histologic analysis in exocrine carcinoma of the pancreas; relation to choice of therapy]. / Indagine cito-istologica intraoperatoria nel carcinoma esocrino del pancreas; rapporto con la scelta terapeutica.

The Authors analyze the various cyto-histology techniques of investigation during surgical operation in the exocrine cancer of the pancreas, both on the results reported in literature and on their experiences based on a sample of 44 patients. They Authors, at the conclusion, single out the preferential technique in the citology by fine needle biopsy, for its reliability, practicality and lack of any complication.