RESUMEN
INTRODUCTION: Cancer stem cells (CSCs) are a subpopulation within a tumor, which possesses the characteristics of self-renewal, differentiation, tumorigenicity, and drug resistance. The aim of this study was to target the colorectal CSC marker CD133 with an(131)I-labeled specific monoclonal antibody (AC133 mAb) in a nude mouse xenograft model. METHODS: Colorectal adenocarcinoma cells (LoVo cell line) were separated into CD133(+) and CD133(-) cells by magnetic activated cell sorting. CD133(+), CD133(-), and unsorted LoVo cells were cultured and then implanted subcutaneously into the lower limbs of nude mice (n = 5). AC133 mAb was labeled with (131)I by the iodogen method. RESULTS: The radiolabeled compound, (131)I-AC133 mAb, showed high stability, specificity, and immunoactivity in vitro. Obvious accumulation of (131)I-AC133 mAb was seen in nude mice bearing xenografts of CD133(+) and unsorted LoVo cells, but no uptake was found in mice bearing CD133(-) xenografts or specifically blocked xenografts. Biodistribution analysis showed that the tumor uptake of (131)I-AC133 mAb was 6.97 ± 1.40, 1.35 ± 0.48, 6.12 ± 1.91, and 1.61 ± 0.44% ID/g (n = 4) at day 7 after injection of (131)I-AC133 mAb in CD133(+), CD133(-), unsorted LoVo cell and specifically blocked xenografts, respectively. The results of immunofluorescence, autoradiography, and western blotting further verified the specific binding of (131)I-AC133 mAb to CD133(+) tumors. CONCLUSIONS: This study demonstrates the possibility of targeting CSCs with a radiolabeled AC133 mAb in colorectal cancer xenografts based on in vitro, ex vivo, and in vivo experiments. Our findings suggest a new method for imaging CSCs non-invasively.
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Anticuerpos Monoclonales/inmunología , Antígenos CD/inmunología , Transformación Celular Neoplásica , Neoplasias Colorrectales/patología , Glicoproteínas/inmunología , Células Madre Neoplásicas/diagnóstico por imagen , Péptidos/inmunología , Antígeno AC133 , Animales , Anticuerpos Monoclonales/farmacocinética , Autorradiografía , Línea Celular Tumoral , Neoplasias Colorrectales/diagnóstico por imagen , Humanos , Ratones , Ratones Desnudos , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos XRESUMEN
There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.
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Neoplasias Hepáticas/patología , Células Madre Neoplásicas/patología , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/patología , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Células Madre Neoplásicas/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To study the cancer stem cell populations in esophageal cancer cell lines KYSE150 and TE1 and identify whether resulting stem-like cell spheres display radiation resistance characteristics. METHODS: Serum-free medium (SFM) suspension was used to culture the esophageal cancer stem cell lines and enrich the esophageal stem-like cell spheres. RT-PCR assay was used to detect the stem cell gene expression in the sphere cells. Radiosensitivity of the sphere cells and parental cells were evaluated by clone formation assay. Different cells after irradiation at different doses were tested to evaluate the changes of sphere formation, and cell cycle and CD44(+)CD271(+) expression of the sphere cells were also analyzed by flow cytometry before and after irradiation. RESULTS: Cancer stem-like cell spheres were generated from KYSE150 and TE1 cells and enriched by culture in serum-free medium, and the number of spheres was increasing alone with the increase of cell passages. The numbers of spheres formed from the 1st, 2nd and 3rd generations of KYSE150 cells were 25 ± 2, 37 ± 2 and 47 ± 3, respectively. The numbers of spheres formed from the 1st, 2nd and 3rd generations of TE1 cells were 15 ± 3, 24 ± 3 and 36 ± 4, respectively. Certain doses of radiation increased the sphere formation rate. The average survival fraction (SF2) of the suspension-cultured KYSE150 stem-like cell spheres after 2 Gy irradiation were 0.81 ± 0.03 and 0.69 ± 0.04, while that of TE1 parental cells were 0.87 ± 0.01 and 0.80 ± 0.03 (P < 0.05 for all). In the esophageal parental KYSE150 and TE1 cells, arrest at G2 phase was induced after irradiation. After the same dose of irradiation, the inhibition of proliferation of the cancer stem cells was lower than that of the parent cells (P < 0.05). After 0, 4 and 8 Gy irradiation, the CD44(+)CD271(+) cell percentage of KYSE150 parental cells were (1.08 ± 0.03)%, (1.29 ± 0.07)% and (1.11 ± 0.09)%; the CD44(+)CD271(+) cell percentage of TE1 parental cells were (1.16 ± 0.11)%, (0.97 ± 0.08)% and (1.45 ± 0.35)% (P > 0.05 for all). After 0, 4 and 8 Gy irradiation, the percentage of CD44(+)CD271(+) cells of KYSE150 stem cell-like spheres were (35.83 ± 1.23)%, (44.90 ± 1.67)% and (57.77 ± 1.88)%, and that of TE1 stem cell-like spheres were (16.07 ± 0.91)%, (22.67 ± 1.12)% and (33.27 ± 1.07)%. Compared the 4 Gy and 8 Gy irradiated KYSE150 and TE1 stem-like cell spheres with the 0 Gy irradiated spheres, the differences were statistically significant (P < 0.05 for all). CONCLUSIONS: The cancer stem cells in KYSE150 and TE1 spheres are more radio-resistant than their parental cells. It may suggest that cancer stem cell populations in the esophageal cancer cells are related to the mechanism of occurrence of radioresistance.
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Línea Celular Tumoral/diagnóstico por imagen , Neoplasias Esofágicas/diagnóstico por imagen , Células Madre Neoplásicas/diagnóstico por imagen , Ciclo Celular , Células Clonales , Citometría de Flujo , Humanos , Tolerancia a Radiación , RadiografíaRESUMEN
AIM: Despite its enormous relevance, homing of hematopoietic stem cells (SCs) remains relatively uncertain due to the limitations of measuring small number of systemically administered cells in the different organs. Despite its high sensitivity, radionuclide detection has been relatively underutilized to this purpose since it cannot differentiate hematopietic SCs recruited by target tissues from those circulating in the blood pool. Our study aims to verify the potential of tracer kinetic approaches in estimating the recruitment of labeled SCs after their systemic administration. METHODS: Twenty-four Lewis rats underwent administration of 2 millions cells labeled with 37 MBq of 99mTc-exametazime. Animals were divided into 2 groups according to administered cells: hematopoietic SCs or cells obtained from a line of rat hepatoma. Cell injection was performed during a planar dynamic acquisition. Regions of interest were positioned to plot time activity curves on heart, lungs, liver and spleen. Blood cell clearance was evaluated according to common stochastic analysis approach. Either fraction of dose in each organ at the end of the experiment or computing the slope of regression line provided by Patlak or Logan graphical approach estimated cell recruitment. At the end of the study, animals were sacrificed and the number of cells retained in the same organs was estimated by in vitro counting. RESULTS: Cell number, documented by the dose fraction retained in each organ at imaging was consistently higher with respect to the "gold standard" in vitro counting in all experiments. An inverse correlation was observed between degree of overestimation and blood clearance of labeled cells (r=-0.56, P<0.05). Logan plot analysis consistently provided identifiable lines, whose slope values closely agreed with the "in vitro" estimation of hepatic and splenic cell recruitment. CONCLUSION: The simple evaluation of organ radioactivity concentration does not provide reliable estimates of local recruitment of systemically administered cells. Yet, the combined analysis of temporal trends of tracer (cell) tissue accumulation and blood clearance can provide quantitative estimations of cell homing in the different organs.
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Butanonas , Rastreo Celular/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/diagnóstico por imagen , Células Madre Neoplásicas/diagnóstico por imagen , Células Madre Neoplásicas/trasplante , Tecnecio , Animales , Masculino , Cintigrafía , Radiofármacos , Ratas , Ratas Endogámicas Lew , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Multiple congenital melanocytic naevi (CMN) in one individual are caused by somatic mosaicism for NRAS mutations; however, the lineage of the mutated cells remains uncertain. OBJECTIVES: To test the hypothesis that CMN may be derived from cutaneous stem cells. METHODS: Sixty-six CMN samples from 44 patients were stained for immunohistochemical (IHC) markers of melanocytic differentiation (TYR, TRP1, TRP2, LEF1, MITF, cKit), pluripotency (nestin, fascin, CD133, CD20, CD34), monocyte/macrophage lineage (CD68, CD163, CD14), proliferation (Ki67) and MTOR/Wnt-signalling pathway activation (pS6, ß-catenin). Semiquantitative scoring compared samples with naevus cell nesting (group 1) with those with only diffuse dermal infiltration (group 2). Transmission electron microscopy (TEM) was performed on 10 samples. RESULTS: A normal melanocyte population was seen overlying many dermal CMN. Group 1 samples were significantly more likely to express melanocytic differentiation markers than group 2, and expression decreased significantly with depth. Expression of these markers was correlated with each other, and with nestin and fascin. CD20 staining was positive in a substantial proportion and was stronger superficially. Expression of ß-catenin and pS6 was almost universal. Some samples expressed monocyte/macrophage markers. TEM revealed variable naevus cell morphology, striking macromelanosomes, double cilia and microvilli. CONCLUSIONS: Congenital melanocytic naevi development frequently coexists with normal overlying melanocyte development, leading us to hypothesize that in these cases CMN are likely to develop from a cell present in the skin independent of, or remaining after, normal melanocytic migration. IHC and TEM findings are compatible with CMN cells being of cutaneous stem-cell origin, capable of some degree of melanocytic differentiation superficially.
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Biomarcadores de Tumor/metabolismo , Células Madre Neoplásicas/diagnóstico por imagen , Nevo Pigmentado/congénito , Neoplasias Cutáneas/congénito , Antígenos de Diferenciación/metabolismo , Antígenos de Neoplasias/metabolismo , Linaje de la Célula , Humanos , Inmunohistoquímica , Microscopía Electrónica de Transmisión , Células Madre Neoplásicas/metabolismo , Nevo Pigmentado/metabolismo , Nevo Pigmentado/ultraestructura , Fenotipo , Piel/citología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/ultraestructura , UltrasonografíaRESUMEN
BACKGROUND: The prostate stem cell antigen (PSCA) is broadly overexpressed on the surface of prostate cancer cells. MATERIALS & METHODS: Anti-human PSCA monoclonal antibody (mAb 7F5) was bound to Fe(3)O(4)/Au (GoldMag) nanoparticles to serve as a PSCA-specific molecular MRI probe (mAb 7F5@GoldMag) for in vivo detection of prostate cancer cells. First, the efficacy of the antibody immobilization for the binding was assessed. Next, PC-3 (human prostate cancer cell line with PSCA overexpression) tumor-bearing mice were injected with mAb 7F5@GoldMag for MRI measurements while using mouse anti-human IgG bound to the particles (IgG@GoldMag) to serve as a nonspecific control. MRI examinations were conducted before and after injection of these probes at 6, 12 and 24 h; T2-weighted signal intensity within the tumors was measured. RESULTS: Targeted binding of the mAb 7F5@GoldMag probe to PC-3 tumors was verified with optical images and MRI; selective binding was not observed for the nonspecific IgG@GoldMag probe. CONCLUSION: MRI measurements suggest the promising efficacy of this new approach for targeted molecular imaging of prostate tumors.
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Antígenos de Neoplasias , Imagen por Resonancia Magnética/métodos , Nanopartículas del Metal , Proteínas de Neoplasias , Neoplasias de la Próstata , Animales , Anticuerpos Antiidiotipos/administración & dosificación , Anticuerpos Antiidiotipos/química , Anticuerpos Inmovilizados/administración & dosificación , Anticuerpos Inmovilizados/química , Antígenos de Neoplasias/química , Antígenos de Neoplasias/inmunología , Proteínas Ligadas a GPI/química , Proteínas Ligadas a GPI/inmunología , Oro/administración & dosificación , Oro/química , Humanos , Masculino , Nanopartículas del Metal/administración & dosificación , Nanopartículas del Metal/química , Ratones , Imagen Molecular , Terapia Molecular Dirigida , Proteínas de Neoplasias/química , Proteínas de Neoplasias/inmunología , Células Madre Neoplásicas/diagnóstico por imagen , Células Madre Neoplásicas/inmunología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/inmunología , RadiografíaRESUMEN
The finding that tumours, like normal tissues, are endowed with varying degrees of cellular heterogeneity has far-reaching consequences for our understanding of cancer. The cancer stem cell and clonal evolution models have both been proposed to explain tumour-associated cellular heterogeneity. Here, we briefly review these two non-exclusive models with special emphasis on how they aid our understanding of cancer and their implications for therapeutic strategies. Finally, we discuss the close association between basic stem cell biology and cancer, focusing on the role of self-renewal.
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Neoplasias/patología , Células Madre Neoplásicas , Antineoplásicos/uso terapéutico , Descubrimiento de Drogas , Humanos , Modelos Biológicos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Células Madre Neoplásicas/diagnóstico por imagen , Células Madre Neoplásicas/patología , UltrasonografíaRESUMEN
OBJECTIVE: To make sure whether Bcrp1 is the marker of cervical cancer stem-like cells or not by studying the characterization of Bcrp1(+) HeLa cells. METHODS: Immunofluorescence stained flow cytometry and electron microscope were used to sort and observe ultrastructures of Bcrp1(+) and Bcrp1(-) HeLa cells. Flow cytometry was used to identify the cycle and the rate of apoptosis with annexin V in two group cells. The expression of proliferating cell nuclear antigen (PCNA) and caspase-3 were tested using western blot method. RESULTS: (1) There were 7.1% Bcrp1(+) cells and 92.9% Bcrp1(-)cells in HeLa cells. Bcrp1(+) HeLa cells were large in size of nuclear and nucleoli are clear, and there were rich of cytomicrosome and rough endoplasmic reticulum. After sorted and cultured for 24, 48, 72 hours, the adhesion in Bcrp1(+) cells were 72.8%, 81.1%, 80.4%, respectively. While, they were 3.3%, 18.7%, 12.6% at each time for Bcrp1(-) cells (all P < 0.05). (2) There are more S phase cells in Bcrp1(+) cells than that in Bcrp1(-) cells (54.1% vs 21.1%, P < 0.05), while the percentage of G(0)/G(1) and G(2)/M in Bcrp1(-) cells were higher than those in Bcrp1(+) cells (53.0% vs 44.4%, 25.9% vs 1.5%; all P < 0.05). The rate of apoptosis in Bcrp1(+) cells was lower than that in Bcrp1(-) cells (0.2% vs 5.3%, P < 0.05). (3) The expression of PCNA in Bcrp1(+) cells was higher than that in Bcrp1(-) cells (3140 vs 2255, P < 0.05), while the expression of caspase-3 of Bcrp1(+) cells was lower than that in Bcrp1(-) cells (1970 vs 3551, P < 0.05). CONCLUSION: There are more vigor and ability of proliferation and lower rate of apoptosis in Bcrp1(+) HeLa cells than those in Bcrp1(-) cells, which may be some characters of cervical cancer stem cells.
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Transportadoras de Casetes de Unión a ATP/metabolismo , Apoptosis , Caspasa 3/metabolismo , Células HeLa , Proteínas de Neoplasias/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Ciclo Celular , Proliferación Celular , Femenino , Citometría de Flujo , Humanos , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/diagnóstico por imagen , Células Madre Neoplásicas/metabolismo , UltrasonografíaRESUMEN
Identification and characterization of cancer-initiating cells (CICs) enriched for stem cell-like functions and the establishment of a link between CICs and tumor recurrence, chemotherapy resistance and radiation resistance, and metastasis have been the focus of cancer research for the last eight years. Although this field has its share of controversies, it is becoming apparent that cells isolated from recurrent or residual tumors or both are enriched for cancer cells that have a specific phenotype compared with heterogeneous cells in the primary tumor. Enrichment of CICs in tumors subjected to radiation therapy could be due in part to the delivery of sublethal doses of treatment and the efficient radical scavenging system within CICs. Sublethal doses of radiation are sufficient to induce senescence of non-CICs while forcing CICs to gain several new properties related to cell cycle progression in addition to maintaining or enhancing stem cell characteristics of pre-treatment CICs. Characterizing pathways responsible for the increase in CICs after therapy and exploiting the unique characteristics of therapy-resistant CICs for developing targeted therapies are becoming a central focus of research in the rapidly evolving field of CICs.
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Neoplasias de la Mama/radioterapia , Ciclo Celular/efectos de la radiación , Proliferación Celular/efectos de la radiación , Células Madre Neoplásicas/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Antígeno CD24/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de la radiación , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , RadiografíaRESUMEN
With evidence emerging in support of a cancer stem-cell model of carcinogenesis, it is of paramount importance to identify and image these elusive cells in their natural environment. The cancer stem-cell hypothesis has the potential to explain unresolved questions of tumorigenesis, tumor heterogeneity, chemotherapeutic and radiation resistance, and even the metastatic phenotype. Intravital imaging of cancer stem cells could be of great value for determining prognosis, as well as monitoring therapeutic efficacy and influencing therapeutic protocols. Cancer stem cells represent a rare population of cells, as low as 0.1% of cells within a human tumor, and the phenotype of isolated cancer stem cells is easily altered when placed under in vitro conditions. This represents a challenge in studying cancer stem cells without manipulation or extraction from their natural environment. Advanced imaging techniques allow for the in vivo observation of physiological events at cellular resolution. Cancer stem-cell studies must take advantage of such technology to promote a better understanding of the cancer stem-cell model in relation to tumor growth and metastasis, as well as to potentially improve on the principles by which cancers are treated. This review examines the opportunities for in vivo imaging of putative cancer stem cells with regard to currently accepted cancer stem-cell characteristics and advanced imaging technologies.
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Imagen por Resonancia Magnética , Microscopía , Neoplasias/patología , Células Madre Neoplásicas/patología , Tomografía de Emisión de Positrones , Animales , Humanos , Microscopía/métodos , Microscopía Fluorescente , Microscopía de Contraste de Fase , Neoplasias/diagnóstico por imagen , Células Madre Neoplásicas/diagnóstico por imagen , Fenotipo , Coloración y Etiquetado/métodosRESUMEN
OBJECTIVE: We evaluated the cytotoxic effect of ultrasonic irradiation at low energy on the viability of normal and leukemic cells and the potential mechanisms of action inducing this cytotoxicity. MATERIALS AND METHODS: Human leukemia cell lines (K562, HL-60, KG1a, and Nalm-6), primary leukemic cells, and normal mononuclear cells are treated by ultrasound at a frequency of 1.8 MHz during various exposure times (acoustical power of 7 mW/mL) and immediately tested for cell viability by the trypan blue exclusion assay. Apoptosis is evaluated by cell morphology, phosphatidylserine exposure, and DNA fragmentation. The mitochondrial potential, glutathione content, caspase-3 activation, PARP cleavage, and bcl-2/bax ratio are tested by flow cytometry. Cloning efficiency is evaluated by assays in methylcellulose. RESULTS: The technique we describe here, using minute amounts of energy and in the absence of any chemical synergy, specifically triggers apoptosis in leukemic cells while necrosis is significantly reduced. Ultrasonic treatment of 20 seconds' duration induces a series of successive phases showing the characteristic features of apoptosis: mitochondrial transmembrane potential disturbances, loss of phosphatidylserine asymmetry, morphological changes, and, finally, DNA fragmentation. In contrast to K562 cells, for which a significant reduction of cloning efficiency is observed, the growth of hematopoietic progenitors is totally unaffected. Ultrasound treatment is also associated with depletion of cellular glutathione content, suggesting a link with the oxidative stress. Moreover, the fact that active oxygen scavengers reduce ultrasonic-induced apoptosis suggests a sonochemical mechanism. CONCLUSION: The cell damage observed after exposure of leukemic cells to ultrasound is associated with the apoptotic process and may be a promising tool for a smooth, specific, and effective ex vivo purging of leukemic cells.
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Apoptosis , Leucemia/patología , Células Madre Neoplásicas/diagnóstico por imagen , Terapia por Ultrasonido , Caspasa 3 , Caspasas/análisis , Supervivencia Celular , Fragmentación del ADN , Depuradores de Radicales Libres/farmacología , Glutatión/análisis , Células HL-60/química , Células HL-60/diagnóstico por imagen , Células HL-60/patología , Histidina/farmacología , Humanos , Radical Hidroxilo , Membranas Intracelulares/diagnóstico por imagen , Células K562/química , Células K562/diagnóstico por imagen , Células K562/patología , Manitol/farmacología , Lípidos de la Membrana/análisis , Mitocondrias/diagnóstico por imagen , Proteínas de Neoplasias/análisis , Células Madre Neoplásicas/química , Células Madre Neoplásicas/patología , Estrés Oxidativo , Fosfatidilserinas/análisis , Poli(ADP-Ribosa) Polimerasas/análisis , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Oxígeno Singlete , Ensayo de Tumor de Célula Madre , Ultrasonografía , Proteína X Asociada a bcl-2RESUMEN
A 99m Tc MIBI prone scintimammography (PSM) was performed in a case of underlying Paget's disease of the breast. 99m Tc MIBI PSM showed a diffuse scintigraphic image like a spread of uptake from the deeply located zones of the breast toward epidermis. In vivo, 99m Tc MIBI PSM represents the spread of neoplastic Paget's cells probably attracted by chemotactic factors released by keratinocytes. This spread in Paget's disease is correlated to neu oncogene overexpression which increases the metastatic activity as a consequence of motility enhancement and growth stimulation effect. These scintigraphic images suggest that 99m Tc MIBI PSM could be relevant in management of Paget's disease of the breast.
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Neoplasias de la Mama/diagnóstico por imagen , Carcinoma in Situ/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Enfermedad de Paget Mamaria/diagnóstico por imagen , Tecnecio Tc 99m Sestamibi , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Factores Quimiotácticos/metabolismo , Epidermis/patología , Femenino , Humanos , Queratinocitos/metabolismo , Mamografía , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/análisis , Células Madre Neoplásicas/química , Células Madre Neoplásicas/diagnóstico por imagen , Células Madre Neoplásicas/patología , Enfermedad de Paget Mamaria/química , Posición Prona , Cintigrafía , Receptor ErbB-2/análisis , UltrasonografíaRESUMEN
We report a case of a sonographically-detected impalpable embryonal cell carcinoma with bulky retroperitoneal metastases. A 34-year-old man, who presented with left flank pain, was presumed to have an extragonadal retroperitoneal germ cell tumor. Scrotal sonography revealed a hypoechoic lesion, 7 mm in diameter, which was histologically diagnosed as a primary embryonal cell carcinoma. Evidence suggested that the primary tumor had grown slowly, as the tumor was well encapsulated. This case suggests that some extragonadal germ cell tumors arise from a primary testicular cancers, and that successful treatment of these tumors should include consideration that they may have arisen as a primary testicular mass.
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Células Madre Neoplásicas/diagnóstico por imagen , Neoplasias Retroperitoneales/secundario , Teratoma/secundario , Neoplasias Testiculares/patología , Adulto , Biopsia , Células Madre de Carcinoma Embrionario , Humanos , Ganglios Linfáticos/cirugía , Masculino , Células Madre Neoplásicas/patología , Neoplasias Testiculares/diagnóstico por imagen , UltrasonografíaRESUMEN
The limitations of the agar suspension culture method for primary culturing of human tumor cells prompted development of a monolayer system optimized for cell adhesion and growth. This method grew 83% of fresh human tumor cell biopsy specimens, cultured and not contaminated, from a heterogeneous group of 396 tumors including lung cancer (93 of 114, 82%); melanoma (54 of 72, 75%); sarcoma (46 of 59, 78%); breast cancer (35 of 39, 90%); ovarian cancer (16 of 21, 76%); and a miscellaneous group consisting of gastrointestinal, genitourinary, mesothelioma, and unknown primaries (78 of 91, 86%). Cell growth was characterized morphologically with Papanicolaoustained coverslip cultures and cytogenetically with Giemsastained metaphase spreads. Morphological features such as nuclear pleomorphism, chromatin condensation, basophilic cytoplasm, and melanin pigmentation were routinely seen. Aneuploid metaphases were seen in 90% of evaluable cultures, with 15 of 28 showing 70% or more aneuploid metaphases. Colony-forming efficiency ranged between 0.01 and 1% of viable tumor cells, with a median efficiency of 0.2%. This culture system uses a low inoculum of 25,000 viable cells per well which permitted chemosensitivity testing of nine drugs at four doses in duplicate from 2.2 X 10(6) viable tumor cells and radiation sensitivity testing at five doses in quadruplicate from 0.6 X 10(6) cells. Cultures were analyzed for survival by computerized image analysis of crystal violet-stained cells. Drug sensitivity studies showed variability in sensitivity and in survival curve shape with exponential cell killing for cisplatin, Adriamycin, and etoposide, and shouldered survival curves for 5-fluorouracil frequently seen. Radiation sensitivity studies also showed variability in both sensitivity and survival curve shape. Many cultures showed exponential cell killing, although others had shouldered survival curves. This method for growing cells from primary human biopsy specimens is more efficient than the agar culture method, enables easier and better biological analysis of the actual cells grown, and permits improved characterization of drug and radiation survival curves.