Reprogramming the tumor metastasis cascade by targeting galectin-driven networks.

A sequence of interconnected events known as the metastatic cascade promotes tumor progression by regulating cellular and molecular interactions between tumor, stromal, endothelial, and immune cells both locally and systemically. Recently, a new concept has emerged to better describe this process by defining four attributes that metastatic cells should undergo. Every individual hallmark represents a unique trait of a metastatic cell that impacts directly in the outcome of the metastasis process. These critical features, known as the hallmarks of metastasis, include motility and invasion, modulation of the microenvironment, cell plasticity and colonization. They are hierarchically regulated at different levels by several factors, including galectins, a highly conserved family of ß-galactoside-binding proteins abundantly expressed in tumor microenvironments and sites of metastasis. In this review, we discuss the role of galectins in modulating each hallmark of metastasis, highlighting novel therapeutic opportunities for treating the metastatic disease.

Exercise Training Decreases Hepatic Injury and Metastases Through Changes in Immune Response to Liver Ischemia/Reperfusion in Mice.

BACKGROUND AND AIMS: Liver ischemia/reperfusion injury (IRI) induces local and systemic inflammation in which neutrophil extracellular traps (NETs) are major drivers. IRI markedly augments metastatic growth, which is consistent with the notion that the liver IRI can serve as a premetastatic niche. Exercise training (ExT) confers a sustainable protection, reducing IRI in some animal models, and has been associated with improved survival in patients with cancer; however, the impact of ExT on liver IRI or development of hepatic metastases is unknown. APPROACH AND RESULTS: Mice were randomized into exercise (ExT) and sedentary groups before liver IRI and tumor injection. Computerized dynamic network analysis of 20 inflammatory mediators was used to dissect the sequence of mediator interactions after ischemia/reperfusion (I/R) that induce injury. ExT mice showed a significant decrease in hepatic IRI and tissue necrosis. This coincided with disassembly of complex networks among inflammatory mediators seen in sedentary mice. Neutrophil infiltration and NET formation were decreased in the ExT group, which suppressed the expression of liver endothelial cell adhesion molecules. Concurrently, ExT mice revealed a distinct population of infiltrating macrophages expressing M2 phenotypic genes. In a metastatic model, fewer metastases were present 3 weeks after I/R in the ExT mice, a finding that correlated with a marked increase in tumor-suppressing T cells within the tumor microenvironment. CONCLUSIONS: ExT preconditioning mitigates the inflammatory response to liver IRI, protecting the liver from injury and metastases. In light of these findings, potential may exist for the reduction of liver premetastatic niches induced by liver IRI through the use of ExT as a nonpharmacologic therapy before curative surgical approaches.

Systemic dissemination of glioblastoma: literature review.

INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant tumor from the central nervous system in adults. However, the presence of systemic metastasis is an extremely rare event. The objective of this study was to review the literature, evaluating the possible biological mechanisms related to the occurrence of systemic metastasis in patients diagnosed with GBM. RESULTS: The mechanisms that may be related to GBM systemic dissemination are the blood-brain barrier breach, often seen in GBM cases, by the tumor itself or by surgical procedures, gaining access to blood and lymphatic vessels, associated with the acquisition of mesenchymal features of invasiveness, resistance to the immune mechanisms of defense and hostile environment through quiescence. CONCLUSIONS: Tumor cells must overcome many obstacles until the development of systemic metastasis. The physiologic mechanisms are not completely clear. Although not fully understood, the pathophysiological understanding of the mechanisms that may be associated with the systemic spread is salutary for a global understanding of the disease. In addition, this knowledge may be used as a basis for a therapy to be performed in patients diagnosed with GBM distant metastasis.

Systemic dissemination of glioblastoma: literature review

SUMMARY INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant tumor from the central nervous system in adults. However, the presence of systemic metastasis is an extremely rare event. The objective of this study was to review the literature, evaluating the possible biological mechanisms related to the occurrence of systemic metastasis in patients diagnosed with GBM. RESULTS: The mechanisms that may be related to GBM systemic dissemination are the blood-brain barrier breach, often seen in GBM cases, by the tumor itself or by surgical procedures, gaining access to blood and lymphatic vessels, associated with the acquisition of mesenchymal features of invasiveness, resistance to the immune mechanisms of defense and hostile environment through quiescence. CONCLUSIONS: Tumor cells must overcome many obstacles until the development of systemic metastasis. The physiologic mechanisms are not completely clear. Although not fully understood, the pathophysiological understanding of the mechanisms that may be associated with the systemic spread is salutary for a global understanding of the disease. In addition, this knowledge may be used as a basis for a therapy to be performed in patients diagnosed with GBM distant metastasis.

RESUMO INTRODUÇÃO: Glioblastoma (GBM) é o tumor maligno mais comum do sistema nervoso central em adultos. Entretanto, metástase a distância de GBM é um evento extremamente raro. O presente estudo teve o objetivo de realizar uma revisão da literatura para avaliar os possíveis mecanismos biológicos relacionados com a ocorrência de metástase a distância de pacientes com diagnóstico de GBM. RESULTADOS: Os mecanismos que podem estar relacionados com a capacidade de disseminação sistêmica do GBM são a quebra de barreira hematoencefálica (BHE) frequentemente vista em GBM, seja pela doença, seja por procedimentos cirúrgicos, dando acesso aos vasos sanguíneos e linfáticos, associada à aquisição de características mesenquimais de invasividade, resistência aos mecanismos de defesa do sistema imunológico e adaptação a hostilidades dos meios distantes por meio de quiescência. CONCLUSÕES: As células tumorais necessitam vencer diversos obstáculos até a formação de uma metástase distante. Apesar de não totalmente esclarecido, o entendimento fisiopatológico dos mecanismos pelos quais podem estar associados à disseminação sistêmica do GBM é salutar para a compreensão global da doença. Além disso, esse conhecimento pode servir de base para a terapia a ser empregada diante do paciente com diagnóstico de GBM com metástase a distância.

c-Kit immunoexpression patterns differ in melanotic and amelanotic canine oral melanomas / Análise qualitativa quanto à diferença da imunoexpressão do gene c-Kit em melanomas melânicos e amelânicos da cavidade oral em cães

Melanomas are the most common oral malignancy in dogs. Cell proliferation and connexin expression has been shown to differ in canine melanotic and amelanotic oral melanomas. This study aimed to analyze the c-Kit protein expression in melanotic and amelanotic melanomas from canine buccal cavity. A total of 34 canine buccal melanomas (19 melanotic and 15 amelanotic).were collected. The amelanotic melanomas presented faster evolution and higher incidence of metastasis than melanotic tumors. A significantly higher number of c-Kit positive cells were observed in amelanotic neoplasms. In addition, the intensity of c-Kit immunolabeling was predominantly stronger in amelanotic melanomas. These results confirm a potential role for c-Kit in canine oral melanomas with clear differences in expression patterns between the two histological types of tumor, melanotic and amelanotic. This study highlights the importance of a detailed study of c-Kit mutations in canine oral melanomas to better understand the molecular mechanisms implicated in the development of this disease(AU)

Melanomas são as mais frequentes neoplasias malignas da cavidade bucal de cães. Sabe-se que a proliferação de células e expressão de conexina diferem em melanomas melanóticos e amelanóticos da cavidade bucal de cães. Este estudo analisou a expressão da proteína c-Kit em melanomas melanóticos e amelanóticos da cavidade bucal canina. Um total de 34 melanomas bucais caninos (19 melanóticos e 15 amelanóticos) foram coletados. Os melanomas amelanóticos apresentaram evolução mais rápida e maior incidência de metástase. Foi constatado um número significativamente maior de células positivas para c-Kit em neoplasias amelanóticas. Além disso, a intensidade de imunomarcação de c-Kit foi predominantemente mais forte em melanomas amelanóticos. Estes resultados confirmam um papel potencial para c-Kit em melanomas orais caninos, com diferenças claras em padrões de expressão entre os dois tipos histológicos de tumor, melanóticos e amelanóticos. Este trabalho destaca a importância de um estudo detalhado das mutações c-Kit em melanomas orais caninos para ser possível a melhor compreensão dos mecanismos moleculares envolvidos no desenvolvimento da doença(AU)

c-Kit immunoexpression patterns differ in melanotic and amelanotic canine oral melanomas / Análise qualitativa quanto à diferença da imunoexpressão do gene c-Kit em melanomas melânicos e amelânicos da cavidade oral em cães

Melanomas are the most common oral malignancy in dogs. Cell proliferation and connexin expression has been shown to differ in canine melanotic and amelanotic oral melanomas. This study aimed to analyze the c-Kit protein expression in melanotic and amelanotic melanomas from canine buccal cavity. A total of 34 canine buccal melanomas (19 melanotic and 15 amelanotic).were collected. The amelanotic melanomas presented faster evolution and higher incidence of metastasis than melanotic tumors. A significantly higher number of c-Kit positive cells were observed in amelanotic neoplasms. In addition, the intensity of c-Kit immunolabeling was predominantly stronger in amelanotic melanomas. These results confirm a potential role for c-Kit in canine oral melanomas with clear differences in expression patterns between the two histological types of tumor, melanotic and amelanotic. This study highlights the importance of a detailed study of c-Kit mutations in canine oral melanomas to better understand the molecular mechanisms implicated in the development of this disease...

Melanomas são as mais frequentes neoplasias malignas da cavidade bucal de cães. Sabe-se que a proliferação de células e expressão de conexina diferem em melanomas melanóticos e amelanóticos da cavidade bucal de cães. Este estudo analisou a expressão da proteína c-Kit em melanomas melanóticos e amelanóticos da cavidade bucal canina. Um total de 34 melanomas bucais caninos (19 melanóticos e 15 amelanóticos) foram coletados. Os melanomas amelanóticos apresentaram evolução mais rápida e maior incidência de metástase. Foi constatado um número significativamente maior de células positivas para c-Kit em neoplasias amelanóticas. Além disso, a intensidade de imunomarcação de c-Kit foi predominantemente mais forte em melanomas amelanóticos. Estes resultados confirmam um papel potencial para c-Kit em melanomas orais caninos, com diferenças claras em padrões de expressão entre os dois tipos histológicos de tumor, melanóticos e amelanóticos. Este trabalho destaca a importância de um estudo detalhado das mutações c-Kit em melanomas orais caninos para ser possível a melhor compreensão dos mecanismos moleculares envolvidos no desenvolvimento da doença...

Concomitant tumor resistance: the role of tyrosine isomers in the mechanisms of metastases control.

Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although previous studies indicated that T-cell-dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In a recently published study, we identified this factor as meta-tyrosine and ortho-tyrosine, 2 isomers of tyrosine that would not be present in normal proteins. In 3 different murine models of cancer that generate CR, both meta- and ortho-tyrosine inhibited tumor growth. Additionally, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isomers were mediated in part by early inhibition of the MAP/ERK pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy in G(0)-phase. Other mechanisms, putatively involving the activation of an intra-S-phase checkpoint, would also inhibit tumor proliferation by accumulating cells in S-phase. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors or after other stressors that may promote the escape of metastases from dormancy, an issue that is of pivotal importance to oncologists and their patients.

NFAT1 transcription factor is central in the regulation of tissue microenvironment for tumor metastasis.

Members of the nuclear factor of activated T cell (NFAT) family of transcription factors were originally described in T lymphocytes but later shown to be expressed in several immune and non-immune cell types. NFAT proteins can modulate cellular transformation intrinsically, and NFAT-deficient (NFAT1-/-) mice are indeed more susceptible to transformation than wild-type counterparts. However, the contribution of an NFAT1-/- microenvironment to tumor progression has not been studied. We have addressed this question by inoculating NFAT1-/- mice with B16F10 melanoma cells intravenously, an established model of tumor homing and growth. Surprisingly, NFAT1-/- animals sustained less tumor growth in the lungs after melanoma inoculation than wild-type counterparts. Even though melanoma cells equally colonize NFAT1-/- and wild-type lungs, tumors do not progress in the absence of NFAT1 expression. A massive mononuclear perivascular infiltrate and reduced expression of TGF-ß in the absence of NFAT1 suggested a role for tumor-infiltrating immune cells and the cytokine milieu. However, these processes are independent of an IL-4-induced regulatory tumor microenvironment, since lack of this cytokine does not alter the phenotype in NFAT1-/- animals. Bone marrow chimera experiments meant to differentiate the contributions of stromal and infiltrating cells to tumor progression demonstrated that NFAT1-induced susceptibility to pulmonary tumor growth depends on NFAT1-expressing parenchyma rather than on bone marrow-derived cells. These results suggest an important role for NFAT1 in radio-resistant tumor-associated parenchyma, which is independent of the anti-tumor immune response and Th1 versus Th2 cytokine milieu established by the cancer cells, but able to promote site-specific tumor growth.

Effect of pro-inflammatory cytokine stimulation on human breast cancer: implications of chemokine receptor expression in cancer metastasis.

Interactions between tumour cells and microenvironments may affect their growth and metastasis formation. In search for a better understanding of the role of cellular mediators in the progression of cancer, we investigated the effect of pro-inflammatory cytokines IL-1, IL-6, TNF-alpha and IFN-gamma on the regulation of expression of chemokine receptors CXCR4, CXCR2, CX3CR1, CCR9, and CCR5 in the human breast cancer cell line MCF-7. Our results showed that IL-1 increased CXCR4 expression whereas TNF-alpha increased CX3CR1, CCR9 and CCR5. Interestingly, this regulation was not homogeneous, emphasizing the inherent heterogeneity in cancer that may be responsive to specific inflammatory microenvironments.

Metástasis inusual de adenocarcinoma prostático a piel de párpado: a propósito de un caso / Unusual metastasis of prostate adenocarcinoma to skin of the eyelid: report of a case

El cáncer metastásico que aparece en el ojo, proviene de un cáncer primario de la mama en mujeres y de los pulmones en el hombre. Otros sitios de origen, menos comunes incluyen la próstata, riñones, tiroides y tracto gastrointestinal. Las metástasis orbitarias de carcinoma de próstata son raras. Se trata de paciente masculino de 72 años de edad quien acudió por presentar clínica de aumento de volumen del párpado superior izquierdo con edema, equimosis de 3 meses de evolución, no doloroso a la palpación con limitación de los movimientos oculares. Se le realizaron 2 biopsias la primera incisional que reportó patrón inflamatorio, posteriormente escisional que reportó neoplasia epitelial maligna poco diferenciada de origen glandular, compatible con adenocarcinoma poco diferenciado de probable origen ecrino. Se le indicó estudios de extensión: 1. RMN de cara y cuello: Componente de aspecto infiltrativo a nivel de párpado y contenido de la órbita izquierda con proptosis secundaria y compromiso del aparato muscular sin afectación nervio óptico. 2. TAC: Tórax, abdomen, pelvis: Adenopatía axilar izquierda y retroperitoneales, múltiples, imágenes metastásica osteoblásticas en todo el esqueleto evaluado, aumento de densidad prostática medidas 4,5 por 3,2 cm. Se le realiza PSA total, libre, relación PSAL/PSAT obteniendo valores anormales y biopsia prostática positiva para ADC prostático. Se inició tratamiento con antiandrógenos + análogos de LHRH. Las metástasis a párpados del adenocarcinoma prostático es una entidad rara, que es necesario sospecharla para el diagnóstico etiológico primario.

Generally, cancer metastatic that appears in eye comes from a primary cancer of the mamma in women and of lungs in man. Other origin places, less common includes prostate, kidneys, thyroid and gastrointestinal tract. Metastasis would orbit of prostate carcinoma they are strange. With everything, there are more than 55 cases indexed in the current literature. Patient masculine 72 years of age who went to present clinic of increase of volume of the left superior lid with edema, ecchymosed of 3 months of evolution, not painful to palpation with limitation of ocular movements. He is carried out 2 biopsies the first incisional which report inflammatory pattern, later on escisional that report wicked epithelial neoplasia little differentiated of glandular origin, compatible with adenocarcinoma little differentiated of probable origin ecrino. Is indicated extension studies: 1. RMN neck: Report component of aspect infiltrating to lid level and content of it orbits her left with secondary proptosis commitment of the muscular apparatus without affectation optic nerve. 2. TAC: Thorax, abdomen, pelvis: Adenopathy axillaries left and retroperitoneal, multiple, images osteoblastic in whole valued skeleton, increase of density measured prostatic 4.5 for 3.2 cm. Carried out total, free PSA, relationship PSAL/PSAT obtaining abnormal securities and biopsy positive prostatic for ADC prostatic. Reason why began treatment with anti-androgens + similar of LHRH. The metastasis to lids of adenocarcinoma prostatic is strange entity but is necessary to suspect for the diagnosis and etiologic primary.

Correlación anatomoclínica: de los tumores malignos de mama / Anatomocínical correlation: of the malignant tumors of breat

El cáncer de mama es una de las causas más importantes de mortalidad en la mujer, su incidencia ha aumentado a nivel mundial. Se realiza un estudio descriptivo, retrospectivo, analítico; basado en la revisión de las historias clínicas de pacientes vistas en el Hospital General del Sur “Dr. Pedro Iturbe”, entre julio 2000-julio 2005; con el propósito de conocer la correlación anatomoclínica de los tumores malignos de mama. La muestra estuvo constituida por 59 pacientes. El grupo etario mayormente afectado fue el de 46 a 55 años de edad con un 45,76 por ciento. Predominó el sexo femenino 98 por ciento, el 18,64 por ciento presentaron antecedentes familiares de cáncer, sólo el 5,08 por ciento reportaron antecedentes familiares de cáncer de mama. El consumo de tabaco representó el 54,23 por ciento de los casos. El tipo histológico más frecuente fue carcinoma ductal 89,83 por ciento, seguido de carcinoma lobulillar y Phyllodes maligno ambos con 3,38 por ciento destacándose que el 100 por ciento eran infiltrantes, el 33,89 por ciento con metástasis a ganglio linfático en un 45 por ciento, y a pleura en un porcentaje menor de 40 por ciento. El cáncer de mama es un grave problema de salud pública, tomando en consideración que en el 100 por ciento de los casos estudiados se encontraron en estadio avanzado. Todo ello, evidencia la necesidad de una mayor atención por parte de los clínicos y el desarrollo de programas educativos y de control para lograr diagnóstico temprano.

Te breast cancer is one of the most important causes of death among women; its incidence has increased in worldwide. A descriptive, retrospective, analytical study was carried out; based on the review of the clinical sheets corresponding to patients with that diagnosis seen in Hospital General del Sur “Dr. Pedro Iturbe”, in a period of time ranging from July 2000 up to July 2005. The objective was to know the anatomic clinical correlation of malignant breast tumors. The sample was composed by 59 patients. The higher percentage corresponded to 46 to 55 age group with 45.76 %. The female group was affected in a 98 %. 18.64 % of patients had family backgrounds of some type of cancer; just 5.08 % reported family backgrounds of breast cancer. On the other hand, tobacco use was reported in 54.23 % of the cases. The more frequent histological type was the ductal carcinoma 89.83 %, followed by the lobulillar carcinoma and malignant Phyllodes with 3.38 % respectively. 100 % of them were infiltrating and 33.89 % with metastasis the lymphatic ganglia in 45 % of the cases, in a lower percentage 40 % to pleura. As a result, breast cancer is a serious public health problem, considering that 100 % of the cases were in a late stage. It is needed physicians to pay more attention to this, developing educative programs and controlling in order to make early diagnosis.

T cells are crucial for the anti-metastatic effect of anti-epidermal growth factor receptor antibodies.

Experimental evidences supporting the epidermal growth factor receptor (EGFR) as an important molecule for tumor metastasis had been accumulated. Currently, anti-EGFR monoclonal antibodies (mAbs) constitute a promising approach for the treatment of patients with metastatic tumors. However, the mechanisms associated with the potent anti-metastatic effect of these mAbs have not been completely elucidated due to the lack of appropriate syngeneic preclinical models. In this paper, we have investigated the effects of 7A7, an antibody specific to murine EGFR, on the metastatic properties of D122 murine lung carcinoma. 7A7 mAb significantly impaired metastatic spread of D122 cells in C57BL/6 mice by direct anti-proliferative and pro-apoptotic effects on tumor metastasis. 7A7 mAb capacity to inhibit EGFR activation on D122 cells could contribute to its anti-metastatic effect. In addition, 7A7 mAb was able to induce in vitro antibody-dependent cell-mediated cytotoxicity on D122 cells. Interestingly, 7A7 mAb treatment increased the number of natural killer cells, T lymphocytes and dendritic cells infiltrating the metastatic sites. More strikingly, depletion of CD8(+) and CD4(+) T cells in vivo completely abrogated the 7A7 mAb anti-metastatic activity whereas function of natural killer cells was irrelevant. This study supports an in vivo role for T cell response in the mechanism of action of anti-EGFR mAbs, suggesting the induction of an adjuvant effect.

Prevalencia de patología mamaria en pacientes que acudieron al Hospital Central de San Cristóbal Dr. José María Vargas: durante los años 1999 a 2005 / Prevalence of breast pathology in patients attending in the Hospital Central de San Cristóbal

Las lesiones de las mamas predominan en el sexo femenino dado a su estructura más compleja, mayor volumen y sensibilidad a la influencia endocrina, grasa adulta, tejido conjuntivo mesenquimal. La enfermedad de la mama se presenta como masas palpables, lesiones inflamatorias, aunque las lesiones benignas son las más frecuentes, el cáncer de mama es la principal causa de muerte en la mujer. El trabajo a continuación tiene como objetivo conocer la frecuencia de la patología mamaria en aquellos pacientes que acudieron al Hospital Central de San Cristóbal para los años 1999-2005. Además de aspectos demográficos como el sexo y grupo etario predominante, la procedencia, y antecedentes familiares. Se realizó un estudio de tipo estadístico, retrospectivo, comparativo, de cohorte transversal, y de investigación exploratoria, descriptiva de datos obtenidos del registro de epidemiología del Hospital Central de San Cristóbal durante el intervalo enero 1999 a mayo 2005. En donde se evidenciaron un total de 88 historias; 17 casos eran con patología benigna de mama, revisándose 12 y de 71 casos con patología maligna solo 41. Resultado que de 53 historias, la patología maligna predomina en un 77 por ciento de los casos, en cuanto al sexo; el femenino (97.5 por ciento), y el masculino en 1 caso (2.4 por ciento), la procedencia Táchira (81.1 por ciento), grupo etario en la patología benigna de 16 a 24 años (58.3 por ciento) y en la maligna superiores a los 43 años (73.1 por ciento), el tratamiento de elección fue la cirugía, es importante destacar que la patología de mama se puede presentar con mucha frecuencia en aquellos pacientes con factores de riesgo, a cualquier edad, por lo que es importante realizarse un autoexamen para prevenirla así como acudir a un especialista al momento de presentarse alguna alteración.

Uso do cogumelo Agaricus sylvaticus como complemento terapêutico em paciente com câncer de mama e metástase pulmonar / Edible mushroom Agaricus sylvaticus used as therapeutics complement in a patient with breast cancer and lung metastasis

Há mais de dois mil anos fitoterápicos têm sido usados de maneira empírica no tratamento de diversas doenças, inclusive o câncer de mama com metástase pulmonar que foi submetido a tratamento com o cogumelo comestível Agaricus sylvaticus (marca registrada Cogumelo do Sol) é aqui relatado. O tratamento foi feito como complemento da tradicional quimioterapia, radioterapia e cirurgia. O sucesso evolutivo observado foi atrribuído ao aumento das células "Natural Killer" do paciente. As células CD-56 (Natural Killer Cells) tem sido observadas, em muitos experimentos laboratoriais como elemento imunológico responsável por atividade anticancerígena em animais e humanos.(au)

The morphology, immunophenotype and distribution of paracortical dendritic leucocytes in lymph nodes regional to cutaneous melanoma.

Our aim was to identify and delineate alterations in the distribution and immunophenotype of the lymphocytes and paracortical dendritic leucocytes (interdigitating dendritic cells; IDCs) in lymph nodes regional to tumours. Using immunocytochemistry and computer-assisted image analysis we examined 65 lymph nodes excised from 47 patients with malignant melanoma. Twenty-nine patients had American Joint Committee on Cancer (AJCC) stage II melanoma (no tumour spread beyond the primary site) and 18 had AJCC stage III disease (metastases in the regional nodes). There were significant differences in the frequency, morphology, immunophenotype and anatomical distribution of the IDCs and in the complexity of their dendritic processes in different areas within individual lymph nodes. We conclude that morphological and phenotypical variations in IDCs correlate with differing levels of antigen presentation. Downregulation of antigen presentation in lymph nodes regional to tumours is most probably mediated by tumour products. Differences in IDC distribution and characteristics in lymph nodes from different anatomical sites must be considered in interpreting studies of nodal morphology and function.

Functional differences between two morphologically distinct cell subpopulations within a human colorectal carcinoma cell line

The LISP-I human colorectal adenocarcinoma cell line was isolated from a hepatic metastasis at the Ludwig Institute, Säo Paulo, SP, Brazil. The objective of the present study was to isolate morphologically different subpopulations within the LISP-I cell line, and characterize some of their behavioral aspects such as adhesion to and migration towards extracellular matrix components, expression of intercellular adhesion molecules and tumorigenicity in vitro. Once isolated, the subpopulations were submitted to adhesion and migration assays on laminin and fibronectin (crucial proteins to invasion and metastasis), as well as to anchorage-independent growth. Two morphologically different subpopulations were isolated: LISP-A10 and LISP-E11. LISP-A10 presents a differentiated epithelial pattern, and LISP-E11 is fibroblastoid, suggesting a poorly differentiated pattern. LISP-A10 expressed the two intercellular adhesion molecules tested, carcinoembryonic antigen (CEA) and desmoglein, while LISP-E11 expressed only low amounts of CEA. On the other hand, adhesion to laminin and fibronectin as well as migration towards these extracellular matrix proteins were higher in LISP-E11, as expected from its poorly differentiated phenotype. Both subpopulations showed anchorage-independent growth on a semi-solid substrate. These results raise the possibility that the heterogeneity found in the LISP-I cell line, which might have contributed to its ability to metastasize, was due to at least two different subpopulations herein identified

Introducción del estado de tumor dormido por resistencia concomitante / Introduction of the state of sleep tumor by concomitant resistance

La resistencia concomitante antitumoral es el fenómeno por el cual un individuo portador de un tumor inhibe el crecimiento de un implante tumoral secundario realizado en un sitio distante del primero. En este trabajo hemos evaluado este fenómeno en ratones eutímicos y atímicos usando 9 tumores con diferente grado de inmunogenicidad. Durante el desarrollo tumoral, se observaron dos picos, temporalmente separados de RC: el primer pico fue detectado sólo con tumores inmunogénicos pequeños (menos de 500 mm3); fue específico de tumor y mediado por mecanismos inmunológicos clásicos dependientes del timo. El segundo pico fue exhibido por tumores grandes (más de 2000 mm3) independientemente y correlacionó con la presencia de un factor(es) del suero (ni anticuerpos ni complemento) que inhibía in vitro la proliferación de las células tumorales... (TRUNCADO)(AU)