RESUMEN
Pancreatic cancer is one of the most aggressive forms of cancer, and treatment options are limited. One therapeutic approach is to use nanoparticles to deliver the active agent directly to pancreatic cancer cells. Nanoparticles can be designed to specifically target cancer cells, minimizing damage to healthy tissues. Silver nanoparticles have the unique ability to absorb light, especially in the near-infrared (NIR) region. In this study, silver nanoparticles functionalized with IgG molecules were synthesized and administered to pancreatic cancer cell lines. Subsequently, the cells were photo-excited using a 2 W 808 nm laser and further examined in PANC-1 pancreatic cancer cell lines. Flow cytometry and confocal microscopy combined with immunochemical staining were used to examine the interaction between photo-excited silver nanoparticles and pancreatic cancer cells. The photothermal therapy based on IgG-functionalized silver nanoparticles in pancreatic cancer induces dysfunction in the Golgi apparatus, leading to the activation of the caspase-3 apoptotic pathway and ultimately resulting in cellular apoptosis. These findings suggest that our proposed IgG nanoparticle laser treatment could emerge as a novel approach for the therapy of pancreatic cancer.
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Apoptosis , Inmunoglobulina G , Nanopartículas del Metal , Neoplasias Pancreáticas , Terapia Fototérmica , Plata , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Humanos , Plata/química , Nanopartículas del Metal/química , Línea Celular Tumoral , Terapia Fototérmica/métodos , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Fototerapia/métodosRESUMEN
AIM: Less than 5% of pancreatic masses represent metastases and differentiation from primitive tumors using endo-scopic ultrasound (EUS) is difficult. The aim of our work was to assess the diagnostic value of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) for pancreatic metastases. MATERIAL AND METHODS: We retrospectively analyzed patients with pancreatic metastasis identified during a 8 year period in a tertiary medical center. RESULTS: We included in the study 20 patients evaluated with EUS and CH-EUS. The primary tumor was localized in the kidney (6 cases), lung (5 cases), colon (3 cases), skin (2 patients) and stomach, breast, ovary and liver (1 patient each). Only 11 patients (55%) (kidney, lung, liver, ovary or skin metastases), presented hypervascularity at EUS and arterial hyperenhancement on CH-EUS, with similar diag-nostic value. All renal metastases were hyperenhanced (the negative predictive value 100%) and the stomach, colon and ovary metastases were hypoenhanced. The fast wash-out of contrast substance was encountered in all cases or renal, pulmonary and digestive metastases, but with 53.3-64.3% specificity for the different origin of pancreatic metastases. CONCLUSIONS: The vascularity assessments on conventional EUS or CH-EUS are similar for pancreatic metastases of different origin. EUS tissue acquisition remains mandatory for the diagnosis.
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Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias Pancreáticas , Medios de Contraste , Endosonografía , Femenino , Humanos , Neoplasias Pancreáticas/patología , Estudios RetrospectivosRESUMEN
ESGE recommends considering the following indications for enteral tube insertion: (i) clinical conditions that make oral intake impossible (neurological conditions, obstructive causes); (ii) acute and/or chronic diseases that result in a catabolic state where oral intake becomes insufficient; and (iii) chronic small-bowel obstruction requiring a decompression gastrostomy.Strong recommendation, low quality evidence.ESGE recommends the use of temporary feeding tubes placed through a natural orifice (either nostril) in patients expected to require enteral nutrition (EN) for less than 4 weeks. If it is anticipated that EN will be required for more than 4 weeks, percutaneous access should be considered, depending on the clinical setting.Strong recommendation, low quality evidence.ESGE recommends the gastric route as the primary option in patients in need of EN support. Only in patients with altered/unfavorable gastric anatomy (e.âg. after previous surgery), impaired gastric emptying, intolerance to gastric feeding, or with a high risk of aspiration, should the jejunal route be chosen.Strong recommendation, moderate quality evidence.ESGE suggests that recent gastrointestinal (GI) bleeding due to peptic ulcer disease with risk of rebleeding should be considered to be a relative contraindication to percutaneous enteral access procedures, as should hemodynamic or respiratory instability.Weak recommendation, low quality evidence.ESGE suggests that the presence of ascites and ventriculoperitoneal shunts should be considered to be additional risk factors for infection and, therefore, further preventive precautions must be taken in these cases.Weak recommendation, low quality evidence.ESGE recommends that percutaneous tube placement (percutaneous endoscopic gastrostomy [PEG], percutaneous endoscopic gastrostomy with jejunal extension [PEG-J], or direct percutaneous endoscopic jejunostomy [D-PEJ]) should be considered to be a procedure with high hemorrhagic risk, and that in order to reduce this risk, specific guidelines for antiplatelet or anticoagulant use should be followed strictly.Strong recommendation, low quality evidence.ESGE recommends refraining from PEG placement in patients with advanced dementia.Strong recommendation, low quality evidence.ESGE recommends refraining from PEG placement in patients with a life expectancy shorter than 30 days.Strong recommendation, low quality evidence*.
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Endoscopía Gastrointestinal , Hemorragia Gastrointestinal , Adulto , Gastrostomía/efectos adversos , Humanos , Intestino DelgadoRESUMEN
ESGE recommends the "pull" technique as the standard method for percutaneous endoscopic gastrostomy (PEG) placement.Strong recommendation, low quality evidence.ESGE recommends the direct percutaneous introducer ("push") technique for PEG placement in cases where the "pull" method is contraindicated, for example in severe esophageal stenosis or in patients with head and neck cancer (HNC) or esophageal cancer.Strong recommendation, low quality evidence.ESGE recommends the intravenous administration of a prophylactic single dose of a beta-lactam antibiotic (or appropriate alternative antibiotic, in the case of allergy) to decrease the risk of post-procedural wound infection.Strong recommendation, moderate quality evidence.ESGE recommends that inadvertent insertion of a nasogastric tube (NGT) into the respiratory tract should be considered a serious but avoidable adverse event (AE).Strong recommendation, low quality evidence.ESGE recommends that each institution should have a dedicated protocol to confirm correct positioning of NGTs placed "blindly" at the patient's bedside; this should include: radiography, pH testing of the aspirate, and end-tidal carbon dioxide monitoring, but not auscultation alone.Strong recommendation, low quality evidence.ESGE recommends confirmation of correct NGT placement by radiography in high-risk patients (intensive care unit [ICU] patients or those with altered consciousness or absent gag/cough reflex).Strong recommendation, low quality evidence.ESGE recommends that EN may be started within 3â-â4 hours after uncomplicated placement of a PEG or PEG-J.Strong recommendation, high quality evidence.ESGE recommends that daily tube mobilization (pushing inward) along with a loose position of the external PEG bumper (1â-â2âcm from the abdominal wall) could mitigate the risk of development of buried bumper syndrome.Strong recommendation, low quality evidence.
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Nutrición Enteral , Gastrostomía , Adulto , Endoscopía Gastrointestinal , Gastrostomía/efectos adversos , HumanosRESUMEN
Pancreatic adenocarcinoma (PDAC) is a disease with a high incidence and a dreary prognosis. Its lack of symptomatology and late diagnosis contribute to the dearth and inefficiency of therapeutic schemes. Studies show that overexpressed epidermal growth factor receptor (EGFR) is a common occurrence, linking this to the progression of pancreatic cancer, although the association between its expression and the survival rate is rather controversial. EGFR-targeted therapy has not shown the results expected, leaving at hand more questions than answers; clearly, there is a need for a better understanding of the molecular pathways involved. Nanoparticles have been used in trying to improve the efficacy of antitumor treatment; thus, using EGFR's ligand, EGF, for nanoconjugation, showed promising results in increasing the cellular uptake mechanisms and apoptosis of the targeted cells.
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Adenocarcinoma/tratamiento farmacológico , Terapia Molecular Dirigida/métodos , Nanopartículas/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Apoptosis , Factor de Crecimiento Epidérmico/metabolismo , Receptores ErbB/química , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologíaRESUMEN
The systemic spread of malignant cells from a primary site, a process termed metastasis represents a global challenge in cancer treatment. There is a real need to develop novel therapy strategies and nanomedicine may have remarkable and valuable contribution through specific and selective delivery of chemotherapeutic agents, through its intrinsic cytotoxic activity or through imaging applications, appealing also in the context of cancer personalized therapy. This review is focused on the applications of nanoparticles in the treatment of metastatic cancer, particularly on the possible effect on cell stabilization, growth inhibition, eventual interaction with adhesion molecules and antiangiogenic effect.
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Quantum dots (QDs), also known as nanoscale semiconductor crystals, are nanoparticles with unique optical and electronic properties such as bright and intensive fluorescence. Since most conventional organic label dyes do not offer the near-infrared (>650 nm) emission possibility, QDs, with their tunable optical properties, have gained a lot of interest. They possess characteristics such as good chemical and photo-stability, high quantum yield and size-tunable light emission. Different types of QDs can be excited with the same light wavelength, and their narrow emission bands can be detected simultaneously for multiple assays. There is an increasing interest in the development of nano-theranostics platforms for simultaneous sensing, imaging and therapy. QDs have great potential for such applications, with notable results already published in the fields of sensors, drug delivery and biomedical imaging. This review summarizes the latest developments available in literature regarding the use of QDs for medical applications.
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Técnicas Biosensibles/métodos , Sistemas de Liberación de Medicamentos/métodos , Puntos Cuánticos , Animales , Técnicas Bacteriológicas/instrumentación , Técnicas Bacteriológicas/métodos , Escherichia coli , Humanos , Leishmania/genética , Leishmania/patogenicidad , Imagen Molecular/métodos , Nanopartículas/química , Nanopartículas/uso terapéutico , Puntos Cuánticos/química , Puntos Cuánticos/uso terapéutico , Puntos Cuánticos/toxicidadRESUMEN
Multidrug-resistant bacterial infections that have evolved via natural selection have increased alarmingly at a global level. Thus, there is a strong need for the development of novel antibiotics for the treatment of these infections. Functionalized carbon nanotubes through their unique properties hold great promise in the fight against multidrug-resistant bacterial infections. This new family of nanovectors for therapeutic delivery proved to be innovative and efficient for the transport and cellular translocation of therapeutic molecules. The current review examines the latest progress in the antibacterial activity of carbon nanotubes and their composites.
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Antibacterianos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Nanocompuestos/química , Nanotubos de Carbono/química , Animales , Antibacterianos/uso terapéutico , Humanos , Nanocompuestos/uso terapéuticoRESUMEN
BACKGROUND: Pathogenic bacteria contribute to various globally important diseases, killing millions of people each year. Various fields of medicine currently benefit from or may potentially benefit from the use of nanotechnology applications, in which there is growing interest. Disease-related biomarkers can be rapidly and directly detected by nanostructures, such as nanowires, nanotubes, nanoparticles, cantilevers, microarrays, and nanoarrays, as part of an accurate process characterized by lower sample consumption and considerably higher sensitivity. There is a need for accurate techniques for pathogenic bacteria identification and detection to allow the prevention and management of pathogenic diseases and to assure food safety. CONCLUSION: The focus of this review is on the current nanoparticle-based techniques for pathogenic bacterial identification and detection using these applications.
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Bacterias/aislamiento & purificación , Nanopartículas/química , Nanotecnología/métodos , Antibacterianos/química , Oro/química , Nanotubos de Carbono/química , Puntos Cuánticos/química , Plata/química , VirulenciaRESUMEN
The issue of multidrug resistance (MDR) has become an increasing threat to public health. One alternative strategy against MDR bacteria would be to construct therapeutic vectors capable of physically damaging these microorganisms. Gold nanoparticles hold great promise for the development of such therapeutic agents, since the nanoparticles exhibit impressive properties, of which the most important is the ability to convert light into heat. This property has scientific significance since is exploited to develop nano-photothermal vectors to destroy bacteria at a molecular level. The present paper summarizes the latest advancements in the field of nanotargeted laser hyperthermia of MDR bacteria mediated by gold nanoparticles.
Asunto(s)
Oro/química , Calor , Terapia por Láser , Nanopartículas del Metal/química , Animales , Antibacterianos/farmacología , Humanos , Hipertermia Inducida , FototerapiaRESUMEN
New technologies in endoscopic ultrasound (EUS) evaluation have been developed because of the need to improve the EUS and EUS-fine needle aspiration (EUS-FNA) diagnostic rate. This paper reviews the principle, indications, main literature results, limitations and future expectations for each of the methods presented. Contrast-enhanced harmonic EUS uses a low mechanical index and highlights slow-flow vascularization. This technique is useful for differentiating solid and cystic pancreatic lesions and assessing biliary neoplasms, submucosal neoplasms and lymph nodes. It is also useful for the discrimination of pancreatic masses based on their qualitative patterns; however, the quantitative assessment needs to be improved. The detection of small solid lesions is better, and the EUS-FNA guidance needs further research. The differentiation of cystic lesions of the pancreas and the identification of the associated malignancy features represent the main indications. Elastography is used to assess tissue hardness based on the measurement of elasticity. Despite its low negative predictive value, elastography might rule out the diagnosis of malignancy for pancreatic masses. Needle confocal laser endomicroscopy offers useful information about cystic lesions of the pancreas and is still under evaluation for use with solid pancreatic lesions of lymph nodes.
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Biopsia con Aguja Fina/métodos , Diagnóstico por Imagen de Elasticidad/métodos , Endosonografía/métodos , Microscopía Confocal/métodos , Páncreas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Medios de Contraste/administración & dosificación , Cistoadenoma Mucinoso/diagnóstico por imagen , Diagnóstico Diferencial , Diagnóstico por Imagen de Elasticidad/instrumentación , Endosonografía/instrumentación , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática , Microscopía Confocal/instrumentación , Estadificación de Neoplasias , Neoplasias Ováricas/diagnóstico por imagen , Páncreas/patología , Neoplasias Pancreáticas/patología , Seudoquiste Pancreático/diagnóstico por imagen , Valor Predictivo de las Pruebas , Ultrasonografía DopplerRESUMEN
We have used albumin (BSA) bound to gold nanoparticles (GNPs) as active vectors to target liver cells. Our incentive to develop an original model of living liver cancer sprang from the ethical drawbacks that hindered the assessment of the selective character and the therapeutic capacity of these nano-biosystems in cancer patients. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Albumin bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed. The extent of necrosis was considerable following laser therapy and at the same time surrounding parenchyma was not seriously affected. The selective photothermal ablation of the malignant liver tissue was obtained after the selective accumulation of BSA bound to GNPs into tumor cells following ex-vivo intra-vascular perfusion.
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Oro/uso terapéutico , Hipertermia Inducida/métodos , Neoplasias Hepáticas/terapia , Nanopartículas del Metal/uso terapéutico , Fototerapia/métodos , Albúmina Sérica Bovina/administración & dosificación , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Nanocápsulas/administración & dosificación , Nanocápsulas/química , Nanoconjugados/uso terapéutico , Albúmina Sérica Bovina/química , Resultado del Tratamiento , Células Tumorales CultivadasRESUMEN
There are serious systemic infections associated with methicillin-resistant Staphylococcus aureus (MRSA) and several other types of bacteria leading to the deaths of millions of people globally. This type of mortality is generally caused by the increasing number of antibiotic-resistant organisms, a consequence of evolution via natural selection. After the synthesis of gold nanoparticles (GNPs) by wet chemistry, bio-functionalization with IgG molecules was performed. Following administration of IgG-GNPs to MRSA cultures at various concentrations and various incubation time laser irradiation was performed. To assess the selectivity and specificity of the proposed treatment the following methods were used: flow cytometry, contrast phase microscopy, and by fluorescence microscopy. The results in our study indicate that following administration of IgG-GNPs biomolecule an extended and selective bacterial death occurs following laser irradiation in a dose dependent manner. Therefore, the new findings might impel studies on these antibacterial nanomaterials and their biological and medical applications.
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Oro/química , Inmunoglobulina G/química , Nanopartículas del Metal/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Antibacterianos/química , Separación Celular , Supervivencia Celular , Sistemas de Liberación de Medicamentos , Citometría de Flujo , Luz , Pruebas de Sensibilidad Microbiana , Microscopía de Fuerza Atómica , Microscopía Confocal , Microscopía Fluorescente , Microscopía de Contraste de Fase , Nanocompuestos/química , Espectrofotometría UltravioletaRESUMEN
Severe infections caused by Methicillin-resistant Staphylococcus aureus (MRSA) and other bacteria are responsible for millions of deaths each year. One of the main objectives of future antibiotic strategies is to develop new anti-infective agents, which would be highly effective and drug-resistant (antimicrobial resistance being currently exhibited by MRSA), using specific antibodies conjugated to thermally active nanomaterials such as NIR-responsive photothermal contrast agents. Multi-walled carbon nanotubes (MWCNTs) covalently functionalized with immunoglobulin G (IgG, an antagonist of Staphylococcal protein A-SpA, which is a MRSA membrane associated protein) were selectively delivered (at various concentrations and incubation times) into MRSA bacteria. Following treatment, cultures were irradiated using an 808 nm 2 w laser diode. The post irradiation death rate ranged from 39.6% (for 1 mg/L) to 79.2% (for 50 mg/L) at 60 seconds (p < 0.001), while at 30 minutes, the death rate increased from 45.2% (1 mg/L) to 85.72% (50 mg/L), p < 0.001. Irradiated MRSAs treated with MWCNTs alone (control) for 60 seconds and 30 minutes, at concentrations ranging from 1 mg/L to 50 mg/L, resulted in significantly lower death rates (7.1-34.1% for 60 seconds, 11.7-48.8% for 30 minutes). Using IgG molecules bound to MWCNTs, followed by laser irradiation, we obtained a very efficacious nanoshell-mediated laser therapy of individual MRSA agents providing highly localized killing effects for IgG-MWCNTs targeted bacteria.
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Desinfección/métodos , Inmunoglobulina G/metabolismo , Terapia por Láser/métodos , Staphylococcus aureus Resistente a Meticilina/fisiología , Staphylococcus aureus Resistente a Meticilina/efectos de la radiación , Nanotubos de Carbono/química , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Inmunoglobulina G/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Nanotubos de Carbono/ultraestructura , Dosis de Radiación , Fármacos Sensibilizantes a Radiaciones/uso terapéuticoRESUMEN
Recent research suggests that nanotechnologies may lead to the development of novel cancer treatment. Gold nanoparticles with their unique physical and chemical properties hold great hopes for the development of thermal-based therapies against human malignancies. This review will focus on various strategies that have been developed to use gold nanoparticles as photothermal agents against human cancers.
RESUMEN
We present a method of enhanced laser thermal ablation of HepG2 cells based on a simple gold nanoparticle (GNP) carrier system such as serum albumin (Alb), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. HepG2 or hepatocytes were treated with Alb-GNPs at various concentrations and various incubation times, and further irradiated using a 2 W, 808 nm laser. Darkfield microscopy and immunochemical staining was used to demonstrate the selective internalization of Alb-GNPs inside the HepG2 cells via Gp60 receptors targeting. The postirradiation apoptotic rate of HepG2 cells treated with Alb-GNPs ranged from 25.8% (for 5 µg/mL) to 48.2% (for 50 µg/mL) at 60 seconds, while at 30 minutes the necrotic rate increased from 35.7% (5 µg/mL) to 52.3% (50 µg/mL), P-value <0.001. Significantly lower necrotic rates were obtained when human hepatocytes were treated with Alb-GNPs in a similar manner. We also showed by means of immunocytochemistry that photothermal treatment of Alb-conjugated GNPs in liver cancer initiates Golgi apparatus-endoplasmic reticulum dysfunction with consequent caspase-3 apoptotic pathway activation and cellular apoptosis. The presented results may become a new method of treating cancer cells by selective therapeutic vectors using nanolocalized thermal ablation by laser heating.
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Caspasa 3/metabolismo , Portadores de Fármacos/química , Oro/química , Neoplasias Hepáticas/patología , Nanopartículas del Metal/química , Albúmina Sérica/metabolismo , Sialoglicoproteínas/metabolismo , Apoptosis , Carcinoma Hepatocelular/patología , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Células Hep G2/efectos de los fármacos , Humanos , Hipertermia Inducida , Inmunohistoquímica , Rayos Láser , Necrosis , FotoquímicaRESUMEN
BACKGROUND AND AIMS: The aim of the current study was to evaluate in vitro the anti-tumor efficacy of gold nanoparticles (GNPs) conjugated with conventional chemotherapy drugs for the treatment of liver cancer. This approach based on gold proposes a novel platform therapy with minimal toxicity and increased efficacy profiles for the destruction of hepatic cancer cells. METHODS: GNPs, stabilized with a monolayer of L-aspartate and additional cytostatic drugs, were successfully used as a complex tumor-targeting drug-delivery system. The drugs (doxorubicin, cisplatin, and capecitabine) were non-covalently conjugated onto the hydrophilic assemblies of GNPs-L-Aspartate nanostructure. Transmission electron microscopy was used to characterize the morphological and structural properties of these drug-metallic nanostructures. RESULTS: The cellular proliferation rates in the presence of the anti-cancer drugs delivered by the GNPs were found to be statistically lower than those of cells exposed to the cytostatic drugs alone, indicating that GNPs facilitated an increased susceptibility of cancer cells to cisplatin, doxorubicin, and capecitabine plus ribavirin. CONCLUSION: This approach could offer a new chemotherapy strategy for patients diagnosed with unresectable hepatocellular carcinoma (HCC).
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Oro , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas del Metal , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Capecitabina , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/ultraestructura , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cisplatino/administración & dosificación , Cisplatino/farmacocinética , Cisplatino/farmacología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Desoxicitidina/farmacología , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Fluorouracilo/farmacocinética , Fluorouracilo/farmacología , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/ultraestructura , Microscopía Electrónica de Transmisión , Células Tumorales CultivadasRESUMEN
BACKGROUND AND OBJECTIVES: The failure of existing treatments for liver cancer has recently been attributed to the existence of cancer stem cells, which are difficult to kill using current drugs due to their chemoresistant properties as well as their ability to stimulate neoangiogenesis. The aim of the current study was to evaluate in vitro the antitumor efficacy of arsenic trioxide in combination with conventional chemotherapy, as proposed by the concept of "differentiation therapy" in anticancer research. MATERIALS AND METHODS: Cancer stem cells showed enhanced chemoresistance to cancer drugs (carboplatin and doxorubicin) and had the ability to exclude rhodamine 123 dye, proving the existence of the multidrug resistance efflux pump. Arsenic trioxide was added prior to a tyrosine kinase inhibitor or to a slightly modified PIAF regimen with capecitabine replacing 5-fluorouracil. We also compared both cancer and normal stem cell lines with the hepG2 non-stem liver cancer cell line to investigate the differences between differentiated and more anaplastic cells. Molecular characterization (immunocytochemistry and RT-PCR analysis) of all the cell lines was carried out. RESULTS: Initially, the cells had a high proliferative potential, even when cultured in a medium supplemented with cytostatics, eliminated rhodamine 123 immediately in culture and also formed spheroids in suspension. The molecular characterization showed the expression of albumin, α1-antitrypsin, α-fetoprotein, citokeratin-18, telomerase, CD90 and CD133. Low concentrations of arsenic trioxide lead to morphologic differentiation and differentiation-associated cytochemical features, like increased sensitivity to cytostatic drugs. CONCLUSION: Our study suggests that arsenic trioxide sensitizes liver stem-like cancer cells to conventional chemotherapy. Still, further studies on animal models will be needed before we implement this idea in human clinical trials.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Antígeno AC133 , Antígenos CD/inmunología , Antígenos CD/metabolismo , Trióxido de Arsénico , Arsenicales/farmacología , Capecitabina , Carcinoma Hepatocelular/patología , Línea Celular , Cisplatino/farmacología , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Colorantes Fluorescentes/química , Fluorouracilo/análogos & derivados , Fluorouracilo/farmacología , Glicoproteínas/inmunología , Glicoproteínas/metabolismo , Células Hep G2 , Humanos , Inmunohistoquímica , Interferón-alfa/farmacología , Neoplasias Hepáticas/patología , Óxidos/farmacología , Péptidos/inmunología , Péptidos/metabolismo , Rodamina 123/química , Antígenos Thy-1/inmunología , Antígenos Thy-1/metabolismoRESUMEN
Magnification chromoendoscopy (MCE) and miniprobes are able to select the tumors suitable for curative endoscopic treatment. Endoscopic submucosal dissection (ESD) is a new endoscopic technique that has a higher complete resection rate and a very low recurrence rate. We present three cases of superficial epithelial digestive tumors that were first evaluated with MCE and miniprobes before being treated by ESD. A complete one-fragment resection was performed with no major complications in all cases.