Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy.

Endometrial cancer is one the most prevalent gynecological cancers and, unfortunately, has a poor prognosis due to low response rates to traditional treatments. However, the progress in molecular biology and understanding the genetic mechanisms involved in tumor processes offers valuable information that has led to the current classification that describes four molecular subtypes of endometrial cancer. This review focuses on the molecular mechanisms involved in the pathogenesis of endometrial cancers, such as genetic mutations, defects in the DNA mismatch repair pathway, epigenetic changes, or dysregulation in angiogenic or hormonal signaling pathways. The preclinical genomic and molecular investigations presented allowed for the identification of some molecules that could be used as biomarkers to diagnose, predict, and monitor the progression of endometrial cancer. Besides the therapies known in clinical practice, targeted therapy is described as a new cancer treatment that involves identifying specific molecular targets in tumor cells. By selectively inhibiting these targets, key signaling pathways involved in cancer progression can be disrupted while normal cells are protected. The connection between molecular biomarkers and targeted therapy is vital in the fight against cancer. Ongoing research and clinical trials are exploring the use of standard therapy agents in combination with other treatment strategies like immunotherapy and anti-angiogenesis therapy to improve outcomes and personalize treatment for patients with endometrial cancer. This approach has the potential to transform the management of cancer patients. In conclusion, enhancing molecular tools is essential for stratifying the risk and guiding surgery, adjuvant therapy, and cancer treatment for women with endometrial cancer. In addition, the information from this review may have an essential value in the personalized therapy approach for endometrial cancer to improve the patient's life.

Cell Culture Model Evolution and Its Impact on Improving Therapy Efficiency in Lung Cancer.

Optimizing cell culture conditions is essential to ensure experimental reproducibility. To improve the accuracy of preclinical predictions about the response of tumor cells to different classes of drugs, researchers have used 2D or 3D cell cultures in vitro to mimic the cellular processes occurring in vivo. While 2D cell culture provides valuable information on how therapeutic agents act on tumor cells, it cannot quantify how the tumor microenvironment influences the response to therapy. This review presents the necessary strategies for transitioning from 2D to 3D cell cultures, which have facilitated the rapid evolution of bioengineering techniques, leading to the development of microfluidic technology, including organ-on-chip and tumor-on-chip devices. Additionally, the study aims to highlight the impact of the advent of 3D bioprinting and microfluidic technology and their implications for improving cancer treatment and approaching personalized therapy, especially for lung cancer. Furthermore, implementing microfluidic technology in cancer studies can generate a series of challenges and future perspectives that lead to the discovery of new predictive markers or targets for antitumor treatment.

Studies Regarding the Antimicrobial Behavior of Clotrimazole and Limonene.

The paper presents the results of the studies performed to establish the effect of the mixtures between limonene and clotrimazole against microbial pathogens involved in dermatological diseases, such as Candida albicans, Staphyloccocus aureus, and Escherichia coli. Preliminary data obtained from the studies performed in microplates revealed a possible synergism between the mixture of clotrimazole and limonene for Staphylococcus aureus. Studies performed "in silico" with programs such as CLC Drug Discovery Workbench and MOLEGRO Virtual Docker, gave favorable scores for docking each compound on a specific binding site for each microorganism. The tests performed for validation, with the clotrimazole (0.1%) and different sources of limonene (1.9% citrus essential oils), showed a synergistic effect on Staphylococcus aureus in the case of the mixtures between clotrimazole and the essential oils of Citrus reticulata or Citrus paradisi. The studies performed on Staphylococcus aureus MRSA showed a synergistic effect between clotrimazole and the essential oils obtained from Citrus bergamia, Citrus aurantium, or Citrus paradisi. In the case of Pseudomonas aeruginosa, essential oils and clotrimazole used alone did not exhibit antimicrobial activities, but the mixtures between clotrimazole and the essential oils of Citrus bergamia or Citrus sinensis exhibited a synergistic antimicrobial effect.

Studies Regarding the Pharmaceutical Potential of Derivative Products from Plantain.

In this study, three types of extracts isolated from leaves of Plantain (Plantago lanceolata) were tested for their chemical content and biological activities. The three bioproducts are combinations of polysaccharides and polyphenols (flavonoids and iridoidic compounds), and they were tested for antioxidant, antifungal, antitumor, and prebiotic activity (particularly for polysaccharides fraction). Briefly, the iridoid-enriched fraction has revealed a pro-oxidant activity, while the flavonoid-enriched fraction had a high antioxidant potency; the polysaccharide fraction also indicated a pro-oxidant activity, explained by the co-presence of iridoid glycosides. All three bioproducts demonstrated moderate antifungal effects against Aspergillus sp., Penicillium sp., and dermatophytes, too. Studies in vitro proved inhibitory activity of the three fractions on the leukemic tumor cell line THP-1, the main mechanism being apoptosis stimulation, while the polysaccharide fraction indicated a clear prebiotic activity, in the concentration range between 1 and 1000 µg/mL, evaluated as higher than that of the reference products used, inulin and dextrose, respectively.

High-Resolution Analysis of Growth and Transpiration of Quinoa Under Saline Conditions.

The Plantarray 3.0 phenotyping platform® was used to monitor the growth and water use of the quinoa varieties Pasto and selRiobamba under salinity (0-300 mM NaCl). Salinity reduced the cumulative transpiration of both varieties by 60% at 200 mM NaCl and by 75 and 82% at 300 mM NaCl for selRiobamba and Pasto, respectively. Stomatal conductance was reduced by salinity, but at 200 mM NaCl Pasto showed a lower reduction (15%) than selRiobamba (35%), along with decreased specific leaf area. Diurnal changes in water use parameters indicate that under salt stress, daily transpiration in quinoa is less responsive to changes in light irradiance, and stomatal conductance is modulated to maximize CO2 uptake and minimize water loss following the changes in VPD (vapor pressure deficit). These changes might contribute to the enhanced water use efficiency of both varieties under salt stress. The mechanistic crop model LINTUL was used to integrate physiological responses into the radiation use efficiency of the plants (RUE), which was more reduced in Pasto than selRiobamba under salinity. By the end of the experiment (eleven weeks after sowing, six weeks after stress), the growth of Pasto was significantly lower than selRiobamba, fresh biomass was 50 and 35% reduced at 200 mM and 70 and 50% reduced at 300 mM NaCl for Pasto and selRiobamba, respectively. We argue that contrasting water management strategies can at least partly explain the differences in salt tolerance between Pasto and selRiobamba. Pasto adopted a "conservative-growth" strategy, saving water at the expense of growth, while selRiobamba used an "acquisitive-growth" strategy, maximizing growth in spite of the stress. The implementation of high-resolution phenotyping could help to dissect these complex growth traits that might be novel breeding targets for abiotic stress tolerance.

Resveratrol Modulation of Apoptosis and Cell Cycle Response to Cisplatin in Head and Neck Cancer Cell Lines.

In head and neck cancers, the effectiveness of cisplatin (CisPt) treatment is limited by its toxicity, especially when higher doses are necessary, and the possible occurrence of cisplatin resistance. This study evaluated the effects of resveratrol (RSV) on the expression of different genes involved in the response of human tumor cells (FaDu, PE/CA-PJ49) to cisplatin therapy. Our results revealed that RSV induced apoptosis amplification in both FaDu and PE/CA-PJ49 cells and modulated the expression of specific genes differently than in normal HaCaT cells. In FaDu cells, combined CisPt + RSV treatment induced an increase in apoptosis, which was associated with an increase in c-MYC and TP53 and a decrease in BCL-2 expression. While CisPt + RSV treatment induced apoptosis in PE/CA-PJ49 cells by inhibition of BCL-2 associated with high levels of MDM-2 and subsequently led to inhibition of TP53 gene expression. Decreased c-MYC expression in PE/CA-PJ49 treated with CisPt + RSV was accompanied by cell cycle blockage in G0/G1 phase. In conclusion, RSV influences tumor cell response to CisPt by inducing apoptosis and modulating gene expression. In addition, in normal HaCaT cells, RSV was able to reduce the harmful effects of CisPt.

The Effect of Resveratrol or Curcumin on Head and Neck Cancer Cells Sensitivity to the Cytotoxic Effects of Cisplatin.

Natural compounds can modulate all three major phases of carcinogenesis. The role of the natural compounds such as resveratrol (RSV) and curcumin (CRM) in modulation of anticancer potential of platinum-based drugs (CisPt) is still a topic of considerable debate. In order to enhance head and neck cancer (HNSCC) cells' sensitivity to the cytotoxic effects of CisPt combined treatments with RSV or CRM were used. The study aim was to evaluate how the RSV or CRM associated to CisPt treatment modulated some cellular processes such as proliferation, P21 gene expression, apoptotic process, and cell cycle development in HNSCC tumor cell line (PE/CA-PJ49) compared to a normal cell line (HUVEC). The results showed that RSV or CRM treatment affected the viability of tumor cells more than normal cells. These natural compounds act against proliferation and sustain the effects of cisplatin by cell cycle arrest, induction of apoptosis and amplification of P21 expression in tumor cells. In conclusion, using RSV or CRM as adjuvants in CisPt therapy might have a beneficial effect by supporting the effects induced by CisPt.

Cisplatin effect on head and neck squamous cell carcinoma cells is modulated by ERK1/2 protein kinases.

The extracellular signal-regulated kinases (ERKs) are key transducers of the extracellular signals into intracellular responses and represent major molecular players in tumorigenesis. The aim of this study was to determine how curcumin (CRM) used as an adjuvant supports the apoptotic process induced by a single chemical agent treatment (cisplatin-CisPT) on two head and neck squamous cell carcinoma cell lines (FaDu and PE/CA-PJ49) and the involvement of ERK1/2 and/or p53 activation in this process. Data have shown that the CisPt effect is potentiated by CRM. CRM induced an increase of p53 protein phosphorylation in both cell lines. CisPt decreased p53 protein phosphorylation in FaDu cells, but increased it in PE/CA-PJ49 cells. Data showed that the constitutive expression of activated ERK1/2 protein-kinase was different in the two analyzed tumor cell lines. ERK1/2 activation status was essential for both cell processes, proliferation and apoptosis induced by CisPt and/or CRM treatment on squamous cell carcinoma cells. Our data suggest that p53 phosphorylation in the apoptotic process induced by CRM treatment might require the involvement of ERK1/2. In this regard the CisPt treatment suggested that p53 phosphorylation is ERK1/2 independent in FaDu cells having a p53 gene deletion and ERK1/2 dependent in PE/CA-PJ49 cells having a p53 gene amplification. Moreover, in both tumor cell lines our results support the involvement of p53 phosphorylation-ERK1/2 activation-dependent in the apoptosis induced by combined treatments (CisPt and CRM). The use of CRM as adjuvant could increase the efficiency of chemotherapy by modulating cellular activation processes of ERK1/2 signaling pathways. In conclusion, the particular mode of intervention by which ERK1/2 might influence cell proliferation and/or apoptosis processes depends on the type of therapeutic agent, the cells' particularities, and the activation status of the ERK1/2.

Concepto sociocultural del VIH y su impacto en la recepción de campañas de promoción de la salud en Medellín / Sociocultural Concept of HIV and its Impact on the Receipt of Health Promotion Campaigns in Medellín / Conceito sociocultural do VIH e o seu impacto na receção de campanhas de promoção da saúde em Medellín

Introducción: desde la aparición de los primeros casos del Síndrome de Inmunodeficiencia Adquirida (SIDA) en Estados Unidos en 1981, se construyó un estigma alrededor de la enfermedad que forjó el concepto sociocultural y los imaginarios respecto a esta, asociando la adquisición del Virus de Inmunodeficiencia Humana (VIH) -virus que desencadena el síndrome- con limitados grupos de población, lo cual propicia un impacto limitado de las campañas emprendidas en la promoción de la salud. Objetivo: comprender el impacto sociocultural del concepto del VIH en las campañas de promoción de la salud desde la percepción de algunos adultos que vivían con la enfermedad en Medellín para el año 2012. Materiales y métodos: se realizó una investigación cualitativa, con enfoque histórico hermenéutico, utilizando la Teoría Fundamentada de Barney Glaser y Anselm Strauss. La información se obtuvo a través de entrevistas realizadas a 13 participantes, cuyas transcripciones se analizaron y categorizaron hasta llegar a la saturación teórica. Resultados: de acuerdo a los informantes clave del estudio, los conceptos socioculturales que se han erigido en torno al VIH se han convertido en una barrera de acceso a los servicios de salud, debido al estigma social, el significado religioso y los mal denominados grupos de riesgo asociados al virus. Discusión: diferentes autores coinciden con los resultados de esta investigación al afirmar que los conceptos socioculturales forjados alrededor del VIH otorgan una mayor complejidad en el abordaje de la enfermedad, lo cual afecta la respuesta a la epidemia desde de sistemas de salud

Introduction: Since the moment in which the first cases of Acquired Immuno-Deficiency Syndrome (AIDS) appeared in the United States in 1981, a stigma was built around the disease which created the social and cultural concept and imagery surrounding the condition. This linked the acquisition of the Human Immunodeficiency Virus (IHV)-the virus that triggers the syndrome- to limited population groups, which in turn led to a limited impact of health promotion campaigns addressing it. Objective: To understand the sociocultural impact of the HIV concept in the health promotion campaigns from the perception of some adults living with the disease in Medellin by 2012. Materials and methods: A qualitative research project with a historical and hermeneutic approach using the Grounded Theory method of Barney Glaser and Anselm Strauss. Data was obtained through interviews with 13 participants. The transcriptions were analyzed and categorized until reaching theoretical saturation. Results: According to key informants of the study, socio-cultural concepts that have been erected around HIV have become a barrier to access health services due to social stigma, religious significance and misnamed group risk associated with the virus. Discussion: The results obtained by a number of authors are consistent with those of this study since they state that the social and cultural concepts surrounding HIV make it more difficult to approach the disease, which in turn affects the health systems' response to this epidemic

Introdução: Desde a aparição dos primeiros casos da Síndrome de Imunodeficiência Adquirida (SIDA) nos Estados Unidos em 1981, construiu-se um estigma ao redor da doença que forjou o conceito sociocultural e os imaginários com respeito a esta, associando a aquisição do Vírus de Imunodeficiência Humana (VIH) -vírus que desencadeia a síndrome- com limitados grupos de população, o qual propicia um impacto limitado das campanhas empreendidas na promoção da saúde. Objetivo: Compreender o impacto sociocultural do conceito do VIH nas campanhas de promoção da saúde desde a percepção de alguns adultos que viviam com a doença em Medellín para o ano 2012. Materiais e métodos: realizou-se uma pesquisa qualitativa, com enfoque histórico hermenêutico, utilizando a Teoria Fundamentada de Barney Glaser e Anselm Strauss. A informação obteve-se através de entrevistas realizadas a 13 participantes, cujas transcrições se analisaram e categorizaram até chegar à saturação teórica. Resultados: de acordo aos informantes chave do estudo, os conceitos socioculturais que se têm erigido em torno ao VIH se têm convertido em uma barreira de acesso aos serviços de saúde, devido ao estigma social, o significado religioso e os mau denominados grupos de risco associados ao vírus. Discussão: diferentes autores coincidem com os resultados desta pesquisa ao afirmar que os conceitos socioculturais forjados ao redor do VIH outorgam uma maior complexidade na abordagem da doença, o qual afeta a resposta à epidemia desde os sistemas de saúde

Relación médico-paciente: impacto en las campañas de promoción y prevención para personas con VIH en Medellín / Physician-patient relationship: Impact on promotion and prevention campaigns for patients with HIV in Medellin

Objetivo Comprender el impacto de los profesionales en salud, en la recepción de campañas de promoción de la salud y prevención de la enfermedad, por parte de la población con VIH de Medellín, Colombia 2012. Materiales y Métodos La investigación se realizó desde un enfoque cualitativo, desarrollando como método la Teoría Fundamentada de Strauss y Corbin. Se entrevistaron trece personas, en dos etapas secuenciales. Las entrevistas fueron transcritas y analizadas siguiendo los criterios de la teoría mencionada, realizando una codificación abierta y axial de los datos encontrados. Resultados Se generaron un total de 1 324 códigos en los procesos de codificación abierta (con la generación de seis categorías descriptivas) y codificación axial (con la generación de cuatro categorías analíticas, siendo una de ellas desarrollada como resultado en este manuscrito), teniendo como hallazgos representativos la relevancia que dieron los participantes al rol de los profesionales de la salud, en cuanto a incorporar estilos de vida saludables para llevar apropiadamente su condición como seropositivos; así mismo, quedó manifiesto el papel que pueden jugar las personas que ya adquirieron el virus en la promoción de conductas sexuales que minimicen el riesgo de contraer la infección. Conclusión La relación médico-paciente plantea grandes desafíos en la gestión de servicios de salud para los diversos actores del sistema, que deben contemplarse en la generación de políticas públicas futuras.(AU)

Objective To understand the impact that healthcare professionals have on the perception of health promotion and disease prevention campaigns of individuals with HIV in Medellin, Colombia in 2012. Materials and Methods: The research was conducted using a qualitative approach, based on the Strauss and Corbin´s Grounded Theory; thirteen people were interviewed during two sequential steps. The interviews were transcribed and analyzed in accordance with the theory mentioned above, by performing an open and axial coding on the data found. Results A total of 1 324 codes were generated in the open coding process (creating six descriptive categories) and axial coding process (identifying four analytical categories; one of them is developed as a result in this paper). The most relevant findings included the importance given by the participants to the role of health professionals when supporting HIV-positive patients in the acquisition of healthy lifestyles to properly manage their condition. Also, the role that those people who already contracted the virus have for the promotion of sexual behaviors to minimize the risk of infection is stated. Conclusion The doctor-patient relationship poses great challenges in terms of health services management for the different actors of the system. Likewise, these challenges must be taken into account when creating future public policies.(AU)

[Physician-patient relationship: Impact on promotion and prevention campaigns for patients with HIV in Medellin]. / Relación médico-paciente: impacto en las campañas de promoción y prevención para personas con VIH en Medellín.

Objective To understand the impact that healthcare professionals have on the perception of health promotion and disease prevention campaigns of individuals with HIV in Medellin, Colombia in 2012. MATERIALS AND METHODS: The research was conducted using a qualitative approach, based on the Strauss and Corbin´s Grounded Theory; thirteen people were interviewed during two sequential steps. The interviews were transcribed and analyzed in accordance with the theory mentioned above, by performing an open and axial coding on the data found. Results A total of 1 324 codes were generated in the open coding process (creating six descriptive categories) and axial coding process (identifying four analytical categories; one of them is developed as a result in this paper). The most relevant findings included the importance given by the participants to the role of health professionals when supporting HIV-positive patients in the acquisition of healthy lifestyles to properly manage their condition. Also, the role that those people who already contracted the virus have for the promotion of sexual behaviors to minimize the risk of infection is stated. Conclusion The doctor-patient relationship poses great challenges in terms of health services management for the different actors of the system. Likewise, these challenges must be taken into account when creating future public policies.

[Influence of HIV related stigma on health care access]. / Influencia del estigma en torno al VIH en el acceso a los servicios de salud.

OBJECTIVE: To notice the influence of the stigma surrounding HIV on the access to health services among the seropositive population of Medellín, Colombia, in 2012. MATERIALS AND METHODS: A qualitative approach using Strauss' and Corbin's grounded theory. Data was collected through 13 interviews at two different moments.These interviews were transcribed and analyzed, and the data found in them was processed via axial and open coding. RESULTS: The myths surrounding HIV become a barrier preventing access to healthcare;this hinders timely treatment of the virus. CONCLUSION: Government policies must aim to reduce the effect that the historical discrimination against HIV has generated so that it can guarantee that infected individuals have early access to treatments for this condition as well as health promotion services.

Influencia del estigma en torno al VIH en el acceso a los servicios de salud / Influence of HIV related stigma on health care access

Objetivo. Reconocer la influencia de los estigmas creados alrededor del VIH en el acceso a los servicios de salud en la población seropositiva de Medellín, Colombia en 2012. Material y métodos. Se parte de un enfoque cualitativo, tomando para el análisis elementos de la teoría fundamentada de Strauss y Corbin. Se entrevistó a 13 personas, en dos momentos diferentes. Las entrevistas fueron transcritas y analizadas; se realizó codificación abierta y axial de los datos encontrados. Resultados. Los mitos erigidos alrededor del VIH se constituyen en una barrera de acceso a los servicios de salud, hecho que configura un retraso en el tratamiento oportuno del virus. Conclusión. Las políticas gubernamentales deben propender por mitigar el impacto que ha generado la histórica discriminación hacia las personas con VIH, para garantizar el acceso temprano por parte de la población infectada a los servicios de promoción de la salud y tratamiento de la enfermedad.

Objective. To notice the influence of the stigma surrounding HIV on the access to health services among the seropositive population of Medellín, Colombia, in 2012. Materials and methods. A qualitative approach using Strauss' and Corbin's grounded theory. Data was collected through 13 interviews at two different moments.These interviews were transcribed and analyzed, and the data found in them was processed via axial and open coding. Results. The myths surrounding HIV become a barrier preventing access to healthcare;this hinders timely treatment of the virus. Conclusion. Government policies must aim to reduce the effect that the historical discrimination against HIV has generated so that it can guarantee that infected individuals have early access to treatments for this condition as well as health promotion services.

Re-establishment of a normal apoptotic process as a therapeutic approach in B-CLL.

Even though the capacity of B-CLL leukemic cells to proliferate has been underestimated until recently, the accumulation of tumor cells in patients mostly results from a defect in the apoptotic program. Several mechanisms can account for this deficient cell death pathway. These include overexpression of anti-apoptotic molecules such as members of the Bcl-2 family, which control the opening of the mitochondrial transition permeability pore, and of the IAP (inhibitors of apoptosis) family, which inhibit the activity of caspases. The latter is also suppressed by nitric oxide (NO) released through an inducible NO synthase present in the leukemic cells. The activity of the receptors with a death domain (Fas, TRAIL) is impaired, thus contributing to the resistance to spontaneous and/or drug-induced apoptosis. Interferons as well as several cytokines and angiogenic factors are also involved in the failure of programmed cell death, either by providing efficient signals for survival (BAFF) or by counteracting the apoptotic process. A better knowledge of the mechanisms of survival and escape from apoptosis of B-CLL cells has led to the proposal of new drugs that selectively interfere at the different steps of these cascades. Their study is complicated by the lack of suitable cell lines and pre-clinical models. Nevertheless, some of these chemotherapeutic agents appear to be promising, provided they are correctly targeted to the leukemic cells.

Comparative antiproliferative and apoptotic effects of resveratrol, epsilon-viniferin and vine-shots derived polyphenols (vineatrols) on chronic B lymphocytic leukemia cells and normal human lymphocytes.

Trans-resveratrol, its dimer epsilon-viniferin and two preparations of vineatrol (a grape-derived polyphenol fraction isolated from vine-shots extracts) were compared for their effects on the proliferation and survival of normal and leukemic human lymphocytes. The two different batches of vineatrol (vineatrol 10 and 25%) was obtained by HPLC fractionation and contained 10 and 25% trans-resveratrol, respectively. The different polyphenols were added to cultures of leukemic cells from chronic B cell malignancies (B-cell chronic lymphocytic leukemia, B-CLL or hairy cell leukemia, HCL) or normal peripheral blood-derived mononuclear cells (PBMC) as a control. The different polyphenols displayed anti-proliferative effect on the leukemic cells, as estimated by the observed inhibition of tritiated thymidine uptake and the reduction of cell recovery. Vineatrol 10% was the most potent whereas vineatrol 25% and resveratrol displayed comparable activity, epsilon-viniferin only exhibiting slight effets. The same order of potency was observed for their capacity to induce apoptosis in leukemic B cells. In contrast, the survival of normal peripheral blood mononuclear cells (PBMC) was little affected in the presence of these polyphenolic compounds and higher concentrations were required in order to elicit cell death. Polyphenol-driven apoptosis in chronic leukemic B cells was shown to correlate with an activation of caspase 3, a drop in the mitochondrial transmembrane potential, a reduction in the expression of the anti-apoptotic protein bcl-2, as well as a reduction in the expression of the inducible nitric oxide synthase (iNOS). Our data therefore indicate that vine-shoots may be a convenient and natural source of material for the purification of resveratrol and other polyphenolic compounds of putative therapeutic interest.

Analysis of resveratrol-induced apoptosis in human B-cell chronic leukaemia.

Trans-resveratrol was analysed for its apoptotic and growth inhibitory activity in human B-cell lines derived from chronic B-cell malignancies (WSU-CLL and ESKOL), and in leukaemic lymphocytes from patients with B-cell chronic lymphocytic leukaemia (B-CLL). Resveratrol displayed antiproliferative activity on both B-cell lines, as estimated by the decrease in cell recovery and inhibition of thymidine uptake. Furthermore, resveratrol induced apoptosis in the two cell lines as well as in B-CLL patients' cells, as evidenced by the increase in annexin V binding, caspase activation, DNA fragmentation and decrease of the mitochondrial transmembrane potential DeltaPsim. We previously reported that nitric oxide (NO), endogenously released by an iNO synthase (iNOS) spontaneously expressed in these leukaemic cells, contributed to their resistance towards apoptosis. We show here that resveratrol inhibited both iNOS protein expression and in situ NO release in WSU-CLL, ESKOL and B-CLL patients'cells. In addition, Bcl-2 expression was also inhibited by resveratrol. Thus, downregulation of the two anti-apoptotic proteins iNOS and Bcl-2 can contribute to the apoptotic effects of resveratrol in leukaemic B cells from chronic leukaemia. Our data suggest that this drug is of potential interest for the therapy of B-CLL.