ABSTRACT
INTRODUCTION: Pituitary neuroendocrine tumors (PitNETs) represent 15-18.2% of all intracranial tumors. Their clinical presentation can range from chronic headache, visual defects, hypopituitarism to hormone excess syndromes. PitNETS are commonly classified as functioning neuroendocrine tumors (F-PitNETs) and non-functioning neuroendocrine tumors (NF-PitNETs). At the moment, new classification has emerged based on cell lineages. Almost 50% of all patients with PitNETs require surgical intervention, and about 25% of these have residual and persistent disease that may require additional management. SUBJECTS AND METHODS: A retrospective cohort of medical records of patients with PitNETs, aiming to describe the incidence of recurrence of patients who received surgical treatment over a 12 month follow up period at San Jose Hospital (SJH) in Bogotá, Colombia, over an observation period of 10 years. Furthermore, clinical presentation, biochemical characteristics and immunohistochemistry, postoperative complications are detailed. RESULTS: Eight hundred and eighty-seven patients with pituitary tumors were included in the cohort; 83% (737/887) had a diagnosis of PitNET. Of these, 18.9% (140) received surgical management. The majority 58% (98/140) had nonfunctional-PitNETs (NF-PitNETs), followed by growth-hormone-secreting pituitary adenoma (22.1%; 33/140), adrenocorticotropic- hormone-secreting pituitary adenoma (9.3%; 13/140), and prolactinomas (9.3%; 13/140). A recurrence was found in 45.71% (64/140), subclassified as biochemical in 15.71% (22/140), controlled with medications in 20% (28/140), and remission occurred in 18.57% (26/140). CONCLUSION: Clinical presentation and incidence of recurrence in patients with PitNETs in a referral center in Colombia are similar to other surgical cohorts with low cure rates and high recurrence.
Subject(s)
ACTH-Secreting Pituitary Adenoma , Adenoma , Neuroendocrine Tumors , Pituitary Neoplasms , Humans , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/epidemiology , Pituitary Neoplasms/therapy , Colombia/epidemiology , Retrospective Studies , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/epidemiology , Neuroendocrine Tumors/surgery , ACTH-Secreting Pituitary Adenoma/surgery , Adenoma/diagnosis , Adenoma/epidemiology , Adenoma/therapy , HormonesABSTRACT
BACKGROUND: Blueberries are among the fruits with the highest antioxidant activity and have been recognized by their health promoting properties. AIM: In vitro study of the anti-proliferative effects of a blueberry extract on a panel of cancer cells from different origin. MATERIALS AND METHODS: A blueberry extract was produced using ethanol as extracting solvent. The anti-proliferative activity of the extract was evaluated against seven tumor cell lines. The properties of blueberry extract to decrease cell adhesion and migration were also investigated. RESULTS: Blueberry extract showed a dose-dependent inhibitory effect on cell proliferation for all cell lines. Non-cytotoxic concentrations of the extract decreased cell adhesion in five of seven cell lines studied and inhibited the migration of MDA-MB-231 and PC-3 tumor cells. CONCLUSION: This work provides additional evidence regarding the ability of blueberry extract to inhibit the growth and decrease cell adhesion and migration of different cancer cell lines in vitro.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Blueberry Plants/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Anthocyanins/analysis , Antineoplastic Agents, Phytogenic/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Cell Adhesion/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Female , Humans , Male , Polyphenols/analysisABSTRACT
Rac1 GTPase signaling pathway has a critical role in the regulation of a plethora of cellular functions governing cancer cell behavior. Recently, it has been shown a critical role of Rac1 in the emergence of resistance mechanisms to cancer therapy. This review describes the current knowledge regarding Rac1 pathway deregulation and its association with chemoresistance, radioresistance, resistance to targeted therapies and immune evasion. This supports the idea that interfering Rac1 signaling pathway could be an interesting approach to tackle cancer resistance.
Subject(s)
Drug Resistance, Neoplasm/genetics , Neoplasms/drug therapy , Neoplasms/radiotherapy , Radiation Tolerance/genetics , rac1 GTP-Binding Protein/physiology , Animals , Humans , Molecular Targeted Therapy , Neoplasms/genetics , Signal Transduction/genetics , Tumor Escape/geneticsSubject(s)
Humans , Combined Modality Therapy/trends , Neoplasms , Neoplasms/drug therapy , Quality of LifeABSTRACT
Tamoxifen is a standard endocrine therapy for estrogen receptor positive breast cancer patients. Despite its success, development of resistance mechanisms is still a serious clinical problem. Deregulation of survival signaling pathways play a key role in tamoxifen resistance, being upregulation of Rac1-PAK1 signaling pathway one of the most important. Here, we report the development of the breast cancer cell model MCF7::C1199 having Rac1 enhanced activity with the aim of evaluating the role of Rac1 in acquired endocrine resistance. These cells not only showed distinctive features of Rac1-regulated process as increased migration and proliferation rates, but also showed that upregulation of Rac1 activity triggered a hormonal-independent and tamoxifen resistant phenotype. We also demonstrated that PAK1 activity increases in response to Tamoxifen, increasing phosphorylation levels of estrogen receptor at Ser305, a key phosphorylation site involved in tamoxifen resistance. Finally, we evaluated the effect of 1A-116, a specific Rac1 inhibitor developed by our group, in tamoxifen-resistant cells. 1A-116 effectively restored tamoxifen anti-proliferative effects, switched off PAK1 activity and decreased estrogen receptor phospho-Ser305 levels. Since combination schemes of novel targeted agents with endocrine therapy could be potential new strategies to restore tamoxifen sensibility, these results show that inhibition of Rac1-PAK1 signaling pathway may provides benefits to revert resistance mechanisms in endocrine therapies.
Subject(s)
Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Protein Kinase Inhibitors/pharmacology , Signal Transduction/drug effects , Tamoxifen/pharmacology , p21-Activated Kinases/antagonists & inhibitors , rac1 GTP-Binding Protein/antagonists & inhibitors , Drug Resistance, Neoplasm/drug effects , Estrogens/pharmacology , Female , Humans , MCF-7 Cells , Models, Biological , Phenotype , Phosphorylation/drug effects , Phosphoserine/metabolism , Up-Regulation/drug effects , p21-Activated Kinases/metabolism , rac1 GTP-Binding Protein/metabolismABSTRACT
The unicortical bone defects in sheep are established model for evaluation of biological properties of graft, but their limitation is related to the defect size and the risk of fracture. However, the models of cortical defects are not well described, defined or patterned. Unicortical Circular Ostectomies in tibias were held in twelve sheep females. The diameter and length of the tibia were measured and filling the bone defect was accompanied by imaging evaluation (X-ray, ultrasound and thermography) for 60 days. In addition, the bone fragment collected was processed for histological study. The sheep of this study had tibias with diameters between 1.2 and 2.0 cm and length from 15.4 to 23.0 centimeters with a 95% confidence interval. By radiographs, ultrasound and thermography were possible to measure and compare the bone defect for up to 60 days. The proposed method can be considered efficient and reproducible.(AU)
Os defeitos ósseos unicorticais em ovinos são modelos muito utilizados para avaliação de propriedades biológicas de enxerto, porém, sua limitação está relacionada com o tamanho do defeito e o risco de fratura. No entanto, alguns modelos de defeitos corticais não estão bem descritos, definidos ou padronizados. Com o objetivo de propor um modelo experimental passível de ser reproduzido em projetos de pesquisa foram realizadas ostectomias circulares unicorticais de 5mm, em tíbias de doze ovinos fêmeas. O diâmetro e o comprimento das tíbias foram mensurados e a realização do defeito ósseo foi acompanhado por meio de exames de imagem (radiográfico, ultrassonográfico e termográfico), no transoperatório e por 60 dias. Um fragmento ósseo foi coletado e avaliado quanto à viabilidade de realização de estudo histológico por meio de microscopia de luz e eletrônica de transmissão. As ovelhas deste estudo possuíam tíbias com diâmetros entre 1,2 e 2,0 centímetros, com comprimento variando de 15,4 a 23,0 centímetros, com intervalo de confiança de 95%. Por meio de exames radiográficos, ultrassonográficos e termográficos foi possível mensurar e comparar o defeito ósseo por até 60 dias, e o método proposto pode ser considerado eficaz por ser adequadamente reprodutível.(AU)
Subject(s)
Animals , Tibia/abnormalities , Tibia/surgery , Sheep/surgery , Bone Regeneration , Models, Animal , Bone Diseases, Developmental/surgeryABSTRACT
Os defeitos ósseos unicorticais em ovinos são modelos muito utilizados para avaliação de propriedades biológicas de enxerto, porém, sua limitação está relacionada com o tamanho do defeito e o risco de fratura. No entanto, alguns modelos de defeitos corticais não estão bem descritos, definidos ou padronizados. Com o objetivo de propor um modelo experimental passível de ser reproduzido em projetos de pesquisa foram realizadas ostectomias circulares unicorticais de 5mm, em tíbias de doze ovinos fêmeas. O diâmetro e o comprimento das tíbias foram mensurados e a realização do defeito ósseo foi acompanhado por meio de exames de imagem (radiográfico, ultrassonográfico e termográfico), no transoperatório e por 60 dias. Um fragmento ósseo foi coletado e avaliado quanto à viabilidade de realização de estudo histológico por meio de microscopia de luz e eletrônica de transmissão. As ovelhas deste estudo possuíam tíbias com diâmetros entre 1,2 e 2,0 centímetros, com comprimento variando de 15,4 a 23,0 centímetros, com intervalo de confiança de 95%. Por meio de exames radiográficos, ultrassonográficos e termográficos foi possível mensurar e comparar o defeito ósseo por até 60 dias, e o método proposto pode ser considerado eficaz por ser adequadamente reprodutível.
ABSTRACT
The unicortical bone defects in sheep are established model for evaluation of biological properties of graft, but their limitation is related to the defect size and the risk of fracture. However, the models of cortical defects are not well described, defined or patterned. Unicortical Circular Ostectomies in tibias were held in twelve sheep females. The diameter and length of the tibia were measured and filling the bone defect was accompanied by imaging evaluation (X-ray, ultrasound and thermography) for 60 days. In addition, the bone fragment collected was processed for histological study. The sheep of this study had tibias with diameters between 1.2 and 2.0 cm and length from 15.4 to 23.0 centimeters with a 95% confidence interval. By radiographs, ultrasound and thermography were possible to measure and compare the bone defect for up to 60 days. The proposed method can be considered efficient and reproducible.
Os defeitos ósseos unicorticais em ovinos são modelos muito utilizados para avaliação de propriedades biológicas de enxerto, porém, sua limitação está relacionada com o tamanho do defeito e o risco de fratura. No entanto, alguns modelos de defeitos corticais não estão bem descritos, definidos ou padronizados. Com o objetivo de propor um modelo experimental passível de ser reproduzido em projetos de pesquisa foram realizadas ostectomias circulares unicorticais de 5mm, em tíbias de doze ovinos fêmeas. O diâmetro e o comprimento das tíbias foram mensurados e a realização do defeito ósseo foi acompanhado por meio de exames de imagem (radiográfico, ultrassonográfico e termográfico), no transoperatório e por 60 dias. Um fragmento ósseo foi coletado e avaliado quanto à viabilidade de realização de estudo histológico por meio de microscopia de luz e eletrônica de transmissão. As ovelhas deste estudo possuíam tíbias com diâmetros entre 1,2 e 2,0 centímetros, com comprimento variando de 15,4 a 23,0 centímetros, com intervalo de confiança de 95%. Por meio de exames radiográficos, ultrassonográficos e termográficos foi possível mensurar e comparar o defeito ósseo por até 60 dias, e o método proposto pode ser considerado eficaz por ser adequadamente reprodutível.
Subject(s)
Animals , Sheep/surgery , Bone Regeneration , Tibia/abnormalities , Tibia/surgery , Bone Diseases, Developmental/surgery , Models, AnimalABSTRACT
Os defeitos ósseos unicorticais em ovinos são modelos muito utilizados para avaliação de propriedades biológicas de enxerto, porém, sua limitação está relacionada com o tamanho do defeito e o risco de fratura. No entanto, alguns modelos de defeitos corticais não estão bem descritos, definidos ou padronizados. Com o objetivo de propor um modelo experimental passível de ser reproduzido em projetos de pesquisa foram realizadas ostectomias circulares unicorticais de 5mm, em tíbias de doze ovinos fêmeas. O diâmetro e o comprimento das tíbias foram mensurados e a realização do defeito ósseo foi acompanhado por meio de exames de imagem (radiográfico, ultrassonográfico e termográfico), no transoperatório e por 60 dias. Um fragmento ósseo foi coletado e avaliado quanto à viabilidade de realização de estudo histológico por meio de microscopia de luz e eletrônica de transmissão. As ovelhas deste estudo possuíam tíbias com diâmetros entre 1,2 e 2,0 centímetros, com comprimento variando de 15,4 a 23,0 centímetros, com intervalo de confiança de 95%. Por meio de exames radiográficos, ultrassonográficos e termográficos foi possível mensurar e comparar o defeito ósseo por até 60 dias, e o método proposto pode ser considerado eficaz por ser adequadamente reprodutível.
ABSTRACT
Receptor-associated coactivator 3 (RAC3) is a nuclear receptor coactivator usually overexpressed in tumors that exerts oncogenic functions in the cytoplasm and the nucleus. Although as part of its oncogenic actions it was previously identified as an inhibitor of apoptosis and autophagy, its expression is required in order to preserve the pluripotency and embryonic stem cell self-renewal. In this work we investigated its role in cellular senescence. We found that RAC3 overexpression in the nontumoral HEK293 cells inhibits the premature senescence induced by hydrogen peroxide or rapamycin. The mechanism involves not only the inhibition of autophagy early induced by these stimuli in the pathway to senescence, but also the increase in levels and nuclear localization of both the cell cycle suppressors p53/p21 and the longevity promoters FOXO1A, FOXO3A and SIRT1. Furthermore, we found that RAC3 overexpression is required in order to maintain the telomerase activity. In tumoral HeLa cells its activity was inhibited by depletion of RAC3 inducing replicative senescence. Moreover, we demonstrated that in vivo, levels of RAC3 are downregulated in the liver from aged as compared with young rats, whereas the levels of p21 are increased, correlating with the expected senescent cell contents in aged tissues. A similar downregulation of RAC3 was observed in the premature and replicative senescence of human fetal WI-38 cells and premature senescence of hepatocyte HepG2 cell line. Taken together, all these results demonstrate that RAC3 is an inhibitor of senescence whose downregulation in aged individuals could be probably a tumor suppressor mechanism, avoiding the clonal expansion of risky old cells having damaged DNA.
Subject(s)
rac GTP-Binding Proteins/physiology , Aging , Animals , Cell Proliferation , Cellular Senescence , Down-Regulation , Female , Gene Expression , Gene Knockdown Techniques , HEK293 Cells , HeLa Cells , Humans , Hydrogen Peroxide/pharmacology , Rats, Wistar , Sirolimus/pharmacologyABSTRACT
BACKGROUND: We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. METHODS: Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. RESULTS: Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens. CONCLUSION: Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.
Subject(s)
Peptides, Cyclic/administration & dosage , Uterine Cervical Neoplasms/drug therapy , Adult , Area Under Curve , Double-Blind Method , Down-Regulation/drug effects , Female , Half-Life , Humans , Injections, Intralesional/methods , Middle Aged , Nuclear Proteins/metabolism , Nucleophosmin , Uterine Cervical Neoplasms/metabolismABSTRACT
Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. Blood-saving agents are attractive compounds to be administered during tumor surgery. Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.
Subject(s)
Deamino Arginine Vasopressin/therapeutic use , Hemostatics/therapeutic use , Neoplasm Recurrence, Local/prevention & control , Neoplasms , Perioperative Care/methods , Animals , Deamino Arginine Vasopressin/administration & dosage , Deamino Arginine Vasopressin/adverse effects , Hemostatics/administration & dosage , Hemostatics/adverse effects , Humans , Neoplasm Metastasis , Neoplasm Recurrence, Local/pathology , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/surgery , Perioperative PeriodABSTRACT
Tissue factor (TF) is a molecular marker that is up-regulated in cancer cells and aids tumoral dissemination. Our purpose was to develop a nested RT-PCR strategy against TF for detecting blood-borne tumour cells. Our method detected TF expression in a minimum of 1.5 pg total RNA from MCF7 cells. A preliminary study in blood samples from 16 advanced breast carcinoma patients showed that 80% of patients with high TF load progressed and died, while only 18% with low TF load showed the same behaviour. Kaplan-Meier analysis confirmed worse overall survival in patients with high TF load.
Subject(s)
Neoplastic Cells, Circulating/metabolism , Neoplastic Cells, Circulating/pathology , Thromboplastin/analysis , Biomarkers/blood , Breast Neoplasms/blood , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Cell Line, Tumor , Disease Progression , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Kaplan-Meier Estimate , Prognosis , Recurrence , Reverse Transcriptase Polymerase Chain Reaction/methods , Sensitivity and Specificity , Thromboplastin/genetics , Thromboplastin/metabolismABSTRACT
In this paper, the dynamics near a 2:3 resonant Hopf-Hopf bifurcation is studied. The main result is the identification of a distinctive structure connecting 1:2 and 1:3 strong resonances of limit cycles. This structure is found near the Hopf-Hopf point revealing that it may be associated to the resonant case, and may provide useful information about the dynamics generated by this codimension 3 bifurcation.
ABSTRACT
Anti-idiotypic monoclonal antibodies (mAb) have been evaluated for actively induced immunotherapy with encouraging results. However, rational combination of cancer vaccines with chemotherapy may improve the therapeutic efficacy of these two approaches used separately. The main objective of this study was to evaluate the antitumor effect of the co-administration of 1E10 (Racotumomab), a monoclonal anti-idiotype tumor vaccine against an IgM mAb, named P3 that reacts specifically with NeuGc-containing gangliosides and low-dose Cyclophosphamide in a mammary carcinoma model. F3II tumor-bearing mice were immunized subcutaneously with 100 microg of 1E10 mAb in Alum or with 150 mg/m(2) of Cyclophosphamide intravenously 7 days after the tumor inoculation. While a limited antitumor effect was induced by a single 1E10 mAb immunization; its co-administration with low-dose Cyclophosphamide reduced significantly the F3II mammary carcinoma growth. That response was comparable with the co-administration of the standard high-dose chemotherapy for breast cancer based on 60 mg/m(2) of Doxorubicin and 600 mg/m(2) of Cyclophosphamide, without toxicity signs. Combinatorial chemo-immunotherapy promoted the CD8(+) lymphocytes tumor infiltration and enhanced tumor apoptosis. Furthermore, 1E10 mAb immunization potentiated the antiangiogenic effect of low-dose Cyclophosphamide. Additionally, splenic myeloid cells Gr1(+)/CD11b(+) associated with a suppressor phenotype were significantly reduced in F3II tumor-bearing mice immunized with 1E10 mAb alone or in combination with low-dose Cyclophosphamide. This data may provide a rational for chemo-immunotherapy combinations with potential medical implications in breast cancer.
Subject(s)
Antibodies, Anti-Idiotypic/therapeutic use , Antibodies, Monoclonal/therapeutic use , Cancer Vaccines/therapeutic use , Gangliosides/immunology , Immunotherapy/methods , Mammary Neoplasms, Experimental/therapy , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Cancer Vaccines/immunology , Cyclophosphamide/pharmacology , Female , Immunohistochemistry , Mammary Neoplasms, Experimental/immunology , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Inbred BALB C , Neovascularization, Pathologic/drug therapyABSTRACT
The present paper reports the presence of 3 adult and juvenile anisakid nematode species: Anisakis simplex, A. brevispiculata, and Pseudoterranova ceticola, which were recovered from the digestive tract of stranded pygmy sperm whales (Kogia breviceps) from 3 localities along the coast of the Yucatan Peninsula. The presence of these anisakid adult nematodes suggests that larval stages may occur in cephalopods or fishes used for human consumption, which represents a potential danger to public health. The occurrence of the 3 anisakid species in coastal waters of the Yucatan Peninsula represents new geographical records for Mexico.
Subject(s)
Ascaridida Infections/veterinary , Ascaridoidea/isolation & purification , Whales/parasitology , Animals , Anisakiasis/parasitology , Anisakiasis/veterinary , Anisakis/classification , Anisakis/isolation & purification , Ascaridida Infections/parasitology , Ascaridoidea/classification , Female , Gastrointestinal Tract/parasitology , Male , MexicoABSTRACT
The presence of substantial amounts of GM3 ganglioside on human melanomas and other tumours, together with its peculiar biological properties, makes this glycolipid a unique target for cancer immunotherapy. B16 mouse melanoma expresses GM3 and constitutes an appropriate model for the development of novel GM3-based vaccines. Recently, we hydrophobically incorporated purified GM3 into the outer membrane protein complex from Neisseria meningitidis to form very small size proteoliposomes (GM3/VSSP). We have examined the antitumour properties of GM3/VSSP vaccine and compared it with GM3 incorporated in very low density serum lipoproteins (GM3/VLDL). Immunization with four doses of GM3/VSSP vaccine (120 microg of ganglioside) plus Freund's adjuvant or Montanide ISA 51 significantly increased the overall survival of mice inoculated in the subcutis with 103 B16-F1 cells, whereas the GM3/VLDL immunogen was ineffective. The non-transient character of tumour protection was confirmed in animals surviving the first challenge and re-inoculated with 5 x 103 cells. GM3/VSSP vaccine also reduced the subcutaneous growth of highly aggressive B16-F10 cells. The importance of ganglioside structure in the tumour-protective effect of GM3/VSSP vaccine was confirmed using GM3 containing N-glycolylneuraminic acid, a ganglioside absent in melanoma cells. Immunostaining and enzyme-linked immunosorbent assay (ELISA) experiments showed a high specificity of immune sera against GM3 and the presence of all four IgG subclasses, with a preponderance of IgG2b and IgG3. In addition, a strong anti-B16 complement-mediated cytotoxicity was induced by vaccination with GM3/VSSP. The present data indicate the molecular specificity of GM3/VSSP vaccine as well as the adjuvant-dependent and non-transient character of tumour protection in the B16 mouse model. These findings suggest that an appropriate GM3 vaccine may be capable of inducing prolonged tumour protection in melanoma patients.