Use of Lymph Node Ultrasound Prior to Sentinel Lymph Node Biopsy in 384 Patients with Melanoma: A Cost-Effectiveness Analysis. / Valor de la ecografía ganglionar previa a la biopsia del ganglio centinela en 384 pacientes con melanoma: análisis de coste-efectividad.

BACKGROUND AND OBJECTIVES: Locoregional lymph node ultrasound is not typically included in guidelines as part of the staging process prior to sentinel lymph node biopsy (SLNB). The objective of the present study was to make a clinical and economic analysis of lymph node ultrasound prior to SLNB. MATERIALS AND METHODS: We performed a retrospective study of 384 patients with clinical stage I-II primary melanoma who underwent locorregional lymph node ultrasound (with or without ultrasound-guided biopsy) prior to SLNB between 2004 and 2015. We evaluated the reliability and cost-effectiveness of the strategy. RESULTS: Use of locorregional lymph node ultrasound avoided SLNB in 23 patients (6%). Ultrasound had a sensitivity of 46% and specificity of 76% for the detection of metastatic lymph nodes that were not clinically palpable. False negatives were significantly more common in patients aged over 60 years and in tumors with a thickness of less than 2mm. The staging process using SLNB and ultrasound with ultrasound-guided biopsy produced an increase of €16.30 in the unit price. Our cost-effectiveness analysis identified the staging protocol with ultrasound and SLNB as the dominant strategy, with a lower cost-effectiveness ratio than the alternative, consisting of SLNB alone (8,095.24 vs. €28,605.00). CONCLUSIONS: Ultrasound with ultrasound-guided biopsy for the diagnostic staging of melanoma prior to SLNB is a useful and cost-effective tool. This procedure does not substitute SLNB, though it does allow to avoid SLNB in a not insignificant proportion of patients.

Prescription refill, patient self-report and physician report in assessing adherence to oral endocrine therapy in early breast cancer patients: a retrospective cohort study in Catalonia, Spain.

AIMS: To compare different methods in order to assess adherence and persistence with oral endocrine therapy in women diagnosed with breast cancer (BC) in Catalonia. MATERIALS AND METHODS: This study covered all women newly diagnosed with stage I, II or IIIa BC and positive hormone receptors at six hospitals in Catalonia (Spain) in 2004. Adherence was assessed on the basis of physician report and patient self-report using a telephone questionnaire. Persistence was measured by refill prescriptions. We used the Kappa index to compare adherence measures and logistic regression to evaluate adherence-related risk factors. RESULTS: The study covered a total of 692 women. Adherence ranged from 92% (self-report) to 94.7% (physician report), depending on the measure used; persistence was 74.7% at 5 years of follow-up. Low concordance between measures was observed (Kappa range: 0.018-0.267). Patients aged 50-74 years showed higher adherence than those aged <50 years. Adherence was also associated with: adjuvant chemotherapy and sequential hormonal therapy. CONCLUSIONS: Concordance between the different measures was remarkably low, indicating the need for further research. Adherence is an issue in the management of BC patients taking oral drugs, and should be assessed in clinical practice.

A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study.

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

Phase II clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neoadjuvant treatment in stages II and IIIA HER2-overexpressing breast cancer patients. GEICAM 2003-03 study.

BACKGROUND: we previously reported a phase I trial of liposome-encapsulated doxorubicin citrate (LD), docetaxel and trastuzumab as neoadjuvant in stages II and IIIA human epidermal growth factor receptor 2-overexpressing breast cancer patients. This study evaluates the efficacy of this regimen in a phase II trial. PATIENTS AND METHODS: patients were treated with LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21days associated with standard trastuzumab dose and pegfilgrastim support. RESULTS: fifty-nine patients were enrolled; median age: 48 years (range 24-71 years); premenopausal patients: 36 (61%); 19 patients (32%) presented stage IIIA disease and 40 patients (67%) stage II; histological grades 2-3 tumors: 50 patients (84%) and estrogen receptor-progesterone receptor negative: 28 patients (47%). In all, 27% achieved a pathological complete response in breast and axilla (grade 5-Miller and Payne classification); 15% of patients achieved grade 4. Clinical and radiological response rates were 86% and 81%, respectively. Forty-two patients (71%) underwent breast-conserving surgery. The main grades 3-4 toxic effects were non-febrile neutropenia (29%) and fatigue (8%). Grade 2 left ventricular ejection fraction decline was observed in nine patients. No congestive heart failure was observed. CONCLUSIONS: LD plus docetaxel combination associated with trastuzumab as neoadjuvant is active in breast cancer and entails a favorable cardiotoxicity profile. This regimen is a new treatment option in these patients.

[Nutritional support and treatment of chylothorax with octreotide]. / Soporte nutricional y tratamiento con octreótido del quilotórax.

Patients with chylothorax present a high risk for malnourishment since continuous loss of chylo leads to a significant impairment of their nutritional status. Chylothorax treatment, which initially is conservative, includes dietary measures and medications such as octreotide that decreases chylothorax flow. In this paper we present the case of a patient with chylothorax treated by means of pleural drainage, parenteral nutrition, and octreotide, and we review the most appropriate nutritional support as well as the efficacy and safety of octreotide in chylothorax therapy. The types of nutritional intervention that may be done are a low-fat diet supplemented with intermediate-chain triglycerides (ICT), fat-free enteral nutrition or EN with a high percentage of ICT, and parenteral nutrition. There is no consensus on which is the most appropriate measure. We found very few comparative studies, and the literature is based on single cases or case series. Some authors consider parenteral nutrition as the first choice, whereas others recommend starting with a specific diet and using parenteral nutrition only in specific cases. Parenteral nutrition must cover the patient's demands together with compensating the protein and energy losses due to chylothorax. The use of lipid emulsions is no contraindicated since they do not reach the lymphatic system. With regards to EN, the formulations may be lipid-free or with low lipid content. There is no agreement on when to start them once the drainage of chylo decreases. There are cases and case series indicating that octreotide use in chylothorax seems to be safe and effective. There is no consensus on when to start the therapy, the most appropriate dose, or the time to withdraw the treatment.

Situation, challenges, and SEOM recommendations for the future of undergraduate education in Oncology in Spain.

PURPOSE: The Spanish Society of Medical Oncology (SEOM, for its Spanish acronym) would like to attest to the relevance of training in Oncology as part of the undergraduate education in Medicine program and issue recommendations to improve said training, with the aim of responding better to the challenges that cancer poses to our society. MATERIALS AND METHODS: The curricula of 42 schools of medicine were reviewed with interviews with at least one teaching medical oncologist from each faculty. The qualitative and opinion analysis was completed by means of an online questionnaire targeting lecturers, resident tutors, and residents in Medical Oncology (MO), enabling the detection of needs and areas for improvement at an organizational level and in terms of skill acquisition. RESULTS: While the number of medical schools with a specific, mandatory program in MO has grown by up to 90%, it has not been accompanied by an increase in independent programs. Instead, they largely consist of programs shared with other specialties (61% of the medical faculties). In most of the undergraduate education programs, Oncology contents are fragmented and approached from the perspective of each organ system. CONCLUSIONS: Despite the positive evolution in recent years, the heterogeneity in Oncology contents during undergraduate education training continues to be remarkable. Cross-sectional programs with an integral vision, taught in the final years of undergraduate medical education would be desirable. Among the recommendations for improvement of training in Medical Oncology, the SEOM proposes that updated, theoretical content be incorporated and clinical practice in Medical Oncology departments be promoted.

Role of boost radiotherapy for local control of pure ductal carcinoma in situ after breast-conserving surgery: a multicenter, retrospective study of 622 patients.

PURPOSE: To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost. METHODS AND MATERIALS: Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011. RESULTS: Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p < 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and > 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose > 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and > 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( > 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup. CONCLUSIONS: Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.

Phase I clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neo-adjuvant treatment in stages II and IIIA, HER2-overexpressing breast cancer patients. GEICAM 2003-03 study.

BACKGROUND: We carried out a phase I clinical trial to establish the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of the combination of liposome-encapsulated doxorubicin citrate (LD) and docetaxel in breast cancer patients. PATIENTS AND METHODS: Patients with HER-2-overexpressing stages II and IIIA breast cancers were treated in different dose cohorts of three patients. The MTD cohort was expanded up to six patients. The patients received LD and docetaxel every 21 days, plus weekly trastuzumab, with pegfilgrastim support. RESULTS: A total of 20 patients were enrolled, 18 of them being assessable for toxicity and response. DLTs observed for this combination were diarrhea, fatigue, febrile neutropenia, stomatitis, myalgia, and nonneutropenic infection (pneumonia). LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21 days have been the MTD, with no episode of DLT observed. Seven patients developed left ventricular ejection fraction decline (six grade 1 and one grade 2). No interruptions of the treatment were needed as a consequence of cardiac toxicity. Pathologic complete response was achieved in eight patients (44%). CONCLUSIONS: The MTD and recommended dose for phase II trials of LD and docetaxel are 50 and 60 mg/m(2), respectively. The achieved results on cardiotoxicity are promising.

Doxorubicin and cyclophosphamide followed by weekly docetaxel as neoadjuvant treatment of early breast cancer: analysis of biological markers in a GEICAM phase II study.

INTRODUCTION: To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. PATIENTS AND METHODS: Patients received 60 mg/m(2) of A and 600 mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. RESULTS: Sixty-three women were included. On an intention-to- treat basis, clinical response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. CONCLUSION: Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer.

Evolution of older patients diagnosed with early breast cancer in Spain between 1998 and 2001 included in El Alamo III project.

INTRODUCTION: An increase in the number of cancer cases is expected in the near future. Breast cancer (BC) mortality rates increase with age even when adjusted for other variables. Here we analyzed BC disease-free survival (BCDFS) and BC specific survival (BCSS) in the El Alamo III BC registry of GEICAM Spanish Breast Cancer Group. MATERIALS AND METHODS: El Alamo III is a retrospective registry of BC patients diagnosed between 1998 and 2001. Patients with stage I-III invasive BC of age groups 55-64 years (y), 70-74 years and ≥ 75 years were included. Patients and tumors characteristics, treatments and recurrences and deaths were analyzed. RESULTS: 4343 patients were included within the following age intervals: 2288 (55-64 years), 960 (70-74 years), and 1095 (≥ 75 years). Older patients (≥ 70 years) were diagnosed with more advanced tumors (stage III) than younger patients (21.5% versus 13.4%, p < 0.0001). Mastectomies were performed more on older patients and they received less chemotherapy than younger patients (66.6% versus 43.1%, p < 0.00001 and 30.8% versus 71.6%, p < 0.0001, respectively). With a median follow-up of 5.9 years, 17.7% patients had BCDFS events in the younger group and 19.8% in the older group (p < 0.0001). A decrease in BCSS was also observed in older patients, either when analyzing patients ≥ 70y (p < 0.0001) and when differentiating by the two older groups (p < 0.0001). CONCLUSIONS: Our study suggests that older BC patients have worse outcomes what can be a consequence of receiving inadequate adjuvant treatments. Specific trials for these patients are warranted to allow us to treat them with the same scientific rigor than younger patients.

SEOM clinical guideline on unknown primary cancer (2017).

Cancer of unknown primary site is a histologically confirmed cancer that manifests in advanced stage, with no identifiable primary site following standard diagnostic procedures. Patients are initially categorized based on the findings of the initial biopsy: adenocarcinoma, squamous-cell carcinoma, neuroendocrine carcinoma, and poorly differentiated carcinoma. Appropriate patient management requires understanding several clinical and pathological features that aid in identifying several subsets of patients with more responsive tumors.

Current controversies in the management of early breast cancer.

Medical professionals in general, and medical oncologists in particular, have highly stressful practices because they are under constant pressure to have the highest-quality, up-to-date evidence available in order to make the right decision for each individual patient. From a practical point of view, being updated on oncological and other medical specialties may seem an insurmountable task because the number of scientific publications has increased dramatically. The use of systematic reviews of randomised controlled trials or the application of results obtained from high-quality randomised controlled trials are some of the most common ways to address this need. Unfortunately, they do not cover all complex clinical situations that the majority of medical oncologists face in their outpatient consultations. In this review, we report the conclusions achieved in a multiexpert meeting where five important controversies in the treatment of breast cancer were analysed. Five highly experienced medical oncologists were required to defend an affirmative answer and another five were required to defend a negative answer for each of the clinical questions. After that, a one-day meeting was organised to debate each clinical question and to reach a consensus. We report here the content of this multi-expert meeting along with the conclusions drawn.

Evaluation and management of chemotherapy-induced cardiotoxicity in breast cancer: a Delphi study.

PURPOSE: While much progress has been made in the treatment of breast cancer, cardiac complications resulting from therapy remain a significant concern. Both anthracyclines and novel targeted agents can inflict cardiac damage. The present study aimed to evaluate the difference between what it is currently done and what standards of care should be used to minimizing and managing cardiac toxicity in breast cancer survivors. METHODS: A two-round multicenter Delphi study was carried out. The panel consisted of 100 oncologists who were asked to define the elected therapies for breast cancer patients, the clinical definition and patterns of cancer drug-derived cardiac toxicity, and those protocols focused on early detection and monitoring of cardiovascular outcomes. RESULTS: Experts agreed a more recent definition of cardiotoxicity. Around 38 % of patients with early-stage disease, and 51.3 % cases with advanced metastatic breast cancer had preexisting risk factors for cardiotoxicity. Among risk factors, cumulative dose of anthracycline ≥450 mg/m2 and its combination with other anticancer drugs, and a preexisting cardiovascular disease were considered the best predictors of cardiotoxicity. Echocardiography and radionuclide ventriculography have been the proposed methods for monitoring changes in cardiac structure and function. Breast cancer is generally treated with anthracyclines (80 %), so that the panel strongly stated about the need to plan a strategy to managing cardiotoxicity. A decline of left ventricular ejection fraction (LVEF) >10 %, to an LVEF value <53 % was suggested as a criterion for changing the dose schedule of anthracyclines, or suspending the treatment of chemotherapy plus trastuzumab until the normalization of the left ventricular function. The use of liposomal anthracyclines was strongly suggested as a treatment option for breast cancer patients. CONCLUSIONS: The present report is the first to produce a set of statements on the prevention, evaluation and monitoring of chemotherapy-induced cardiac toxicity in breast cancer patients.

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

HER-2 gene amplification by chromogenic in situ hybridisation (CISH) compared with fluorescence in situ hybridisation (FISH) in breast cancer-A study of two hundred cases.

The purpose of the study was to compare two methods used to analyse HER-2 gene amplification (fluorescence in situ hybridisation (FISH) and chromogenic in situ hybridisation (CISH)), and determine the accuracy of the antibodies CB11 and HercepTest for immunohistochemical detection of HER-2 overexpression from archival breast cancer tissue. Additionally, interobserver variability in the interpretation of CISH and immunohistochemical tests was measured. Two hundred cases of invasive breast carcinoma diagnosed between 2000 and 2003 were selected. Immunohistochemistry (IHC) was performed with HercepTest and CB11, and gene amplification was determined by FISH (PathVision, Vysis) and CISH (Zymed) using tissue macroarrays. An excellent concordance (94.8%) was found between CISH and FISH. Considering FISH as gold standard, sensitivity of CISH was 97.5% and specificity 94%. Overall interobserver agreement of CISH was 97.5% and of IHC 84%. Both antibodies showed a sensitivity of 95.2% and a specificity of 70.7% (CB11) and 81.2% (HercepTest). Our results show that CISH is a highly accurate, reproducible and practical technique to determine HER-2 gene amplification. CB11 and HercepTest are good screening methods with a high sensitivity. The performance of tissue macroarrays to test HER-2 status by IHC, FISH and CISH has demonstrated to be an available and effective method to study large series of tumours.

SEOM Clinical Guideline for bone metastases from solid tumours (2016).

Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.

SEOM Clinical Guideline of fertility preservation and reproduction in cancer patients (2016).

Chemotherapy and radiotherapy often result in reduced fertility in cancer patients. With increasing survival rates, fertility is an important quality-of-life concern for many young cancer patients. Around 70-75% of young cancer survivors are interested in parenthood but the numbers of patients who access fertility preservation techniques prior to treatment are significantly lower. Moreover, despite existing guidelines, healthcare professionals do not address fertility preservation issues adequately. There is a critical need for improvements in clinical care to ensure patients are well informed about infertility risks and fertility preservation options and to support them in their reproductive decision-making prior to cancer treatment.

Interleukin-13 stimulates interleukin-6 production by human keratinocytes. Similarity with interleukin-4.

Interleukin-13 (IL-13) is a recently described human lymphokine which is produced by activated T-cells. Its effect on the production of IL-6 by normal keratinocytes and keratinocyte cell lines of human origin was studied and compared to that of IL-4. IL-13, similarly to IL-4, stimulated IL-6 expression by these cells in a dose- and time-dependent manner. Contamination with endotoxin was excluded by the use of polymyxin B and heat-inactivated cytokines. Further, we showed that IL-13, like IL-4, not only stimulated IL-6 production but also was able to induce overexpression of this cytokine in response to an inflammatory signal such as lipopolysaccharide (LPS). In a previous study, we demonstrated that IL-13, by inhibiting IL-6 and other cytokines produced by monocytes, exhibited an 'anti-inflammatory profile' comparable to that displayed by IL-4. In contrast, we show here that IL-13, by stimulating IL-6 production by keratinocytes, may favour the installation of an inflammatory process at a local level and, here again, it acted like IL-4. Therefore, according to the type of target cell these two 'TH2 type' cytokines induce similar opposing effects on IL-6 production and are likely to be important cytokines in the regulation of inflammation at both systemic and local levels.

Stimulation of peripheral cannabinoid receptor CB2 induces MCP-1 and IL-8 gene expression in human promyelocytic cell line HL60.

Using the recently developed methodology of nucleic acid microarrays spotted with specific cDNAs probes belonging to different gene families, we showed for the first time that nanomolar concentrations of the cannabinoid ligand CP-55940 upregulated the expression of two different members of the chemokine gene family: the alpha-chemokine interleukin-8 (IL-8) and the beta-chemokine monocyte chemotactic protein-1 (MCP-1), in the promyelocytic cell line HL60 transfected with peripheral cannabinoid receptors (CB2). These genomic modulations observed on large-scale cDNA arrays were first confirmed by Northern blot studies. Furthermore, ELISA evaluations in culture supernatants indicated that the cannabinoid-induced activation of these two chemokine genes was followed by enhanced expression and secretion of the corresponding proteins. These upregulations initially observed in transfected HL60 cells overexpressing CB2 receptors, also occurred in normal non-transfected HL60 cells. The enhancement of IL-8 and MCP-1 gene transcription and protein production was shown to be pertussis toxin sensitive attesting that this phenomenon was a Gi protein-coupled receptor-mediated process as expected for cannabinoid receptors. More specifically, the abolition of the cannabinoid-induced effect by the specific CB2 antagonist SR 144528 indicated a strict peripheral cannabinoid-mediated process. Altogether, our data highlight a possible new function of peripheral cannabinoid receptors in the modulation of immune and inflammatory responses.