RESUMEN
AIM: The present study reports our experience concerning with the advanced cancer treatment (cytoreductive surgery and hyperthermic intraperitoneal chemotherapy) in patients with advanced ovarian cancer ephitelial (AEOS) or recurrent ovarian cancer ephitelial (REOC). METHODS: In a period from October 2006 to December 2009, we observed 25 patients affected by advanced ephitelial ovarian cancer or recurrent ephitelial ovarian cancer. All patients underwent CRS + HIPEC procedures. Peritoneal involvement was valued according to the Peritoneal Cancer Index (PCI) and the remaining postoperative disease according to the Completeness of Cytoreduction score (CC). HIPEC was always performed with closed technique for 60 min, with an average inflow temperature of 42.5 °C. The drugs were administered in combination according two schemes: 1) cisplatin 60 mg/m2/L and caelyx 20 mg/m2/L; 2) 60 mg/m2/L taxotere and caelyx 20 mg/m2/L. Morbidity and mortality were evaluated in accordance with the NCI CTCAE v. 3.0 (USA). Finally, the Disease Free Survival and Overall Survival by the Kaplan-Meier method was rated. RESULTS: The average age observed was 64 years (range 46-76). Fourteen patients (56%) were affected by AEOC. From this group, 12 (48%) were subjected to neoadjuvant therapy and 2 (8%) to surgery as a first; 11 (44%) patients had REOC and all of them had previously undergone to surgery and adjuvant CHT. The average PCI was 12.63 (range 2-27). In 22 patients (88%), cytoreduction was considered total or almost total (CC-0 in 14 patients, CC-1 in 8); in 3 patients (12%), it had not been optimal (CC-2 or CC-3). In all 18 patients with PCI less than 15, it was possible to achieve an optimal cytoreduction, and this was possible only in 3 of the 7 patients who had a PCI greater than 15. The average operative time, including HIPEC, was of 612 min (range 425 min-840 min). In 9 patients (36%), the postoperative course was uncomplicated, in 10 patients (40%) complications were minor (G1-G2) and in 4 patients (16%) morbidity was important (G4). Mortality rate was 8%. The average OS was 30.8 months and the median OS was 30.8 months (respectively 36.5 months for AEOC and 27 months for REOC). The median DFS total (calculated from the day of surgery or from the day of the beginning of the CHT) was 12months (respectively 12.9 months for AEOC, 11.9 months for REOC). CONCLUSION: Although the CRS and HIPEC procedure in the treatment of advanced or recurrent ovarian cancer represents now a reliable method with good results both in terms of morbidity and of distance results, there are still many controversial aspects that may in the future be better clarified only with a randomized phase III study, which is in progress, involving international working groups and experts on the procedure.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/secundario , Hipertermia Inducida , Laparotomía/métodos , Neoplasias Ováricas/patología , Neoplasias Peritoneales/secundario , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma/tratamiento farmacológico , Carcinoma/cirugía , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Estudios de Cohortes , Terapia Combinada , Supervivencia sin Enfermedad , Docetaxel , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Humanos , Infusiones Parenterales , Estimación de Kaplan-Meier , Tiempo de Internación/estadística & datos numéricos , Persona de Mediana Edad , Terapia Neoadyuvante , Epiplón/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Peritoneo/cirugía , Polietilenglicoles/administración & dosificación , Complicaciones Posoperatorias/epidemiología , Recurrencia , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
Laryngopharyngeal reflux (LPR) indicates the reflux-induced extra-esophageal disorders. LPR and gastroesophageal reflux disease (GERD) occur by the same mechanism: the escape of gastric contents into the esophagus and beyond. However, the classic GERD symptoms are not typical in LPR disease, which can cause a lot of symptoms none of which is specific, making the diagnosis often elusive. The protective mechanisms present in the esophagus are entirely lacking in the larynx, and more generally in upper aerodigestive tract, making them particularly vulnerable to injury from acidic gastric contents. Since gastric acid backflow can affect supraesophageal structures, even in the absence of heartburn or regurgitation symptoms, an early diagnosis is important to prevent the onset of histological modifications in the supraesophageal mucosa. For this scope clinicians need to use different methods to get a diagnosis. We adopted two validated scoring systems: the reflux symptom index (RSI) for symptom assessing and the reflux finding score (RFS) for sign evaluation. In our experience we detect a new objective endoscopic rhinopharyngeal marker, called "white-line" characterized by mucosal metaplasia, that in a significant proportion of patients lines up to these validated indexes as a further element in the LPR diagnosis.
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Biomarcadores , Reflujo Laringofaríngeo/diagnóstico , Membrana Mucosa/patología , Nasofaringe/patología , Adulto , Biopsia/métodos , Femenino , Humanos , Reflujo Laringofaríngeo/patología , Masculino , Metaplasia/patología , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Uterine smooth muscle tumours that cannot be diagnosed unequivocally as benign or malignant should be termed 'smooth muscle tumours of uncertain malignant potential' (STUMP). Since there are no unequivocal morphological and ancillary criteria to differentiate this group of tumours, we present a case of a 49-year-old woman with a combined, benign and borderline lesion, which could have different clinical management strategies, and discuss the diagnostic issues.
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Leiomioma/patología , Tumor de Músculo Liso/patología , Neoplasias Uterinas/patología , Biomarcadores de Tumor/análisis , Femenino , Humanos , Inmunohistoquímica , Leiomioma/metabolismo , Persona de Mediana Edad , Tumor de Músculo Liso/metabolismo , Neoplasias Uterinas/metabolismoRESUMEN
We describe the brain MR imaging findings of a woman who developed neurologic symptoms due to an acute hyperammonemic encephalopathy resulting from late onset ornithine transcarbamylase deficiency (OCTD). MR images revealed injury (hyperintense foci on long TR images) to the subcortical white matter of the left precentral and supramarginal gyrus and in the left frontal lobe. These findings presumably reflect the distribution of brain injury from hypoperfusion secondary to severe hyperammonemia. If MR findings suggesting hypoperfusion are detected in a patient with hyperammonemia, the diagnosis of OCTD should be considered. Knowledge of the physiopathological mechanisms of OTCD and of MR imaging of hyperammonemic injury may help expedite diagnosis and treatment and prevent the exitus of patients with this genetic disorder.
RESUMEN
Over the last two decades, easier and less expensive stimulation treatments have been largely replaced by more complex and more demanding protocols. Since the mid-nineties, long-term gonadotrophin-releasing hormone agonist stimulation protocols have been widely used. Such lengthy expensive regimens are not free from short- and long-term risks and complications. Mild stimulation protocols reduce the mean number of days of stimulation, the total amount of gonadotrophins used and the mean number of oocytes retrieved. The proportion of high quality and euploid embryos seems to be higher compared with conventional stimulation protocols and the pregnancy rate per embryo transfer is comparable. Moreover, the reduced costs, the better tolerability for patients and the less time needed to complete an IVF cycle make mild approaches clinically and cost-effective over a given period of time. However, further prospective randomized studies are needed to compare cumulative pregnancy rates between the two protocols. Natural cycle IVF, with minimal stimulation, has been recently proposed as an alternative to conventional stimulation protocols in normo- and poor responder patients. Although acceptable results have been reported, further large prospective randomized studies are needed to better evaluate the efficacy of these minimal regimens compared with conventional stimulation approaches.
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Inducción de la Ovulación/métodos , Adulto , Transferencia de Embrión , Femenino , Fertilización In Vitro/métodos , Hormona Liberadora de Gonadotropina/agonistas , Humanos , Folículo Ovárico/fisiología , Embarazo , Índice de EmbarazoRESUMEN
PURPOSE: To report pre- and post-operative macular optical coherence tomography (OCT) and immunohistochemical findings in a case of long-lasting silicone oil tamponade followed by silicone oil removal and epimacular membrane peeling. METHODS: A 69-year-old man with long-standing silicone oil tamponade and an epiretinal membrane at the posterior pole in his right eye (RE) underwent silicone oil/BSS exchange with epiretinal membrane peeling. Preoperatively, RE best-corrected visual acuity was 20/200 and macular OCT examination revealed a small increase in foveal thickness (250 microm) with the appearance of a linear hyper-reflective signal at the foveal vitreoretinal interface and a thicker (440 microm) hyperreflective finding causing posterior shadowing at the vitreoretinal interface inferiorly to the fovea. Histopathologic and immunohistochemical study of the specimen including the epiretinal membrane was performed. RESULTS: Light microscopy revealed extensive rounded empty spaces interpreted as silicone oil bubbles in the preretinal membrane. Macrophages marker (CD68) positive staining cells were found surrounding the empty spaces within the preretinal membrane and several empty spaces were observed intracellularly within macrophage cytoplasm. Thirty days after surgery best-corrected visual acuity was 20/60 and OCT examination showed an evident decrease in foveal thickness (220 microm) with the disappearance of any hyper-reflective signal at the vitreoretinal interface referable to an epiretinal membrane. CONCLUSIONS: The immunohistochemical study showed both silicone oil droplets and macrophagic cells embedded in the epiretinal membrane. Postoperative OCT demonstrated retinal recovery after silicone oil removal and epiretinal membrane peeling, thus justifying an unexpected visual acuity recovery despite the very long term tamponade.
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Membrana Epirretinal/patología , Cuerpos Extraños en el Ojo/patología , Aceites de Silicona , Anciano , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Membrana Epirretinal/etiología , Membrana Epirretinal/cirugía , Humanos , Técnicas para Inmunoenzimas , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Desprendimiento de Retina/complicaciones , Desprendimiento de Retina/cirugía , Tomografía de Coherencia Óptica , Agudeza Visual , Vitrectomía , Vitreorretinopatía Proliferativa/complicaciones , Vitreorretinopatía Proliferativa/cirugíaRESUMEN
We have evaluated the effects of dexamethasone (Dex) alone or in combination with interleukin (IL)-10 or transforming growth factor-beta 1 (TGF-beta 1) on human T cell proliferation. Both IL-10 and TGF-beta 1 significantly decreased the Dex concentration needed to inhibit T cell proliferation by 50% (IC50). Dex in combination with IL-10 completely inhibited T cell proliferation, even when IL-10 alone was ineffective, as in the case of phytohemagglutinin-induced T cell proliferation. The evaluation of the results according to the isobole method displayed a potent synergistic activity between Dex and IL-10, whereas the combination of Dex with TGF-beta 1 was additive. IL-10, but not TGF-beta 1, enhanced the inhibitory effect of Dex on IL-2 production. IL-2 and IL-4 only partly antagonized the antiproliferative effect of the combinations. IL-4 was as effective as IL-2 in antagonizing the combination of Dex with TGF-beta 1, but significantly less effective against the combination of Dex with IL-10. IL-10 and TGF-beta 1 are thus able to potentiate the Dex inhibitory effect on T cell proliferation and could be regarded as potential agents for future immunosuppressive protocols.
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Dexametasona/farmacología , Inmunosupresores/farmacología , Interleucina-10/farmacología , Activación de Linfocitos/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Interleucina-2/biosíntesis , Interleucina-2/genética , Interleucina-2/farmacología , Interleucina-4/farmacología , ARN Mensajero/análisis , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
A role in tumor progression has been proposed for transforming growth factor-beta 1 (TGF beta 1) and interleukin (IL)-8 as well as for IL-1, which itself induces the production of TGF beta 1 and IL-8 in many cell types. TGF beta 1 and IL-8 production and their regulation by IL-1 in five non-small-cell (NSC) lung tumor cell lines were evaluated. Moreover, their levels were evaluated in 29 NSC lung tumors. All cell lines constitutively produced TGF beta 1, and three produced IL-8. After IL-1 beta treatment, TGF beta 1 production was upregulated in two cell lines, whereas IL-8 production was markedly upregulated in two, induced in one, and unmodified in two. In tumors, the levels of TGF beta 1, IL-8, and IL-1 beta were higher than in normal counterparts (p < 0.001), and a positive correlation between IL-8 and IL-1 beta levels (p < 0.001) was found. TGF beta 1, IL-8, and IL-1 beta mRNA expression was examined in 12 tumors. TGF beta 1 mRNA was detected in all cases, IL-8 mRNA in 7, and IL-1 beta MRNA was undetectable. TGF beta 1, IL-8, and IL-1 beta immunoreactivity was then studied by immunohistochemistry. TGF beta 1 and IL-8 immunoreactivity was observed in neoplastic cells; IL-1 beta immunoreactivity was observed in mononuclear cells. In conclusion, in tumors IL-1 beta levels positively correlated with those of IL-8, and IL-1 beta as well as TGF beta 1 and IL-8 levels were significantly higher than in normal tissues.
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Adenocarcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Interleucina-1/análisis , Interleucina-8/análisis , Neoplasias Pulmonares/patología , ARN Mensajero/análisis , ARN Neoplásico/análisis , Factor de Crecimiento Transformador beta/análisis , Adenocarcinoma/inmunología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Células Escamosas/inmunología , Humanos , Inmunohistoquímica , Interleucina-1/inmunología , Neoplasias Pulmonares/inmunología , Células Tumorales CultivadasRESUMEN
The antiestrogen tamoxifen is thought to antagonize the effects of estrogens by competing with them for estrogen receptor (ER) binding. However, tarnoxifen can also reverse multidrug resistance, synergize with cisplatin cytotoxicity, and inhibit growth in ER-negative lung cancer cells. In addition to ERs, rat and human target tissues contain a second binding macromolecule termed the type II estrogen binding site (type II EBS). It has been shown that tamoxifen and flavonoids, a widely distributed class of natural substances with a variety of biologic actions, bind to type II EBS and inhibit the growth of several tumor cell types. At present, conflicting data about ERs and an absence of data about type II EBSs exist for lung tumors. We have tested non-small-cell lung carcinoma cell lines and primary tumor cells for the presence of ERs and type II EBSs and have evaluated the effects of tamoxifen and quercetin (pentahydroxyflavone) on the growth of these cells. Using a whole-cell assay and nuclear and cytosolic radiobinding experiments with [3H]estradiol as tracer, we have found that SK-LU1, SW900, ChaGo-K-1, H441, H661, and A549 cells, as well as primary tumors, bind estrogen specifically. This binding results mainly from the presence of a large number of type II EBSs, whereas ERs are absent or present at low concentrations. Type II EBSs bound tamoxifen and quercetin with similar affinity. Cell counts and a thymidine incorporation assay showed that both compounds inhibit cell growth in a concentration-dependent manner at concentrations ranging from 10 nM to 1 microM. Neither ipriflavone, an isoflavone, nor rutin, the 3-rhamnosylglucoside of quercetin, bound type II EBSs or inhibited cell growth. These findings suggest that tamoxifen and quercetin could regulate lung cancer cell growth through a binding interaction with type II EBSs. This mechanism could also be active in vivo, in that we have observed that nuclear and cytosolic type II EBSs were present in all primary lung cancers tested (n = 12), and that tamoxifen and quercetin were effective in inhibiting in vitro bromodeoxyuridine (BrdU) incorporation and proliferation-cell nuclear antigen expression by neoplastic cells in these cancers.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Quercetina/toxicidad , Receptores de Estrógenos/metabolismo , Tamoxifeno/toxicidad , Anciano , Analgésicos/farmacología , Animales , Unión Competitiva , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , División Celular/efectos de los fármacos , Línea Celular , Núcleo Celular/metabolismo , Citosol/metabolismo , ADN de Neoplasias/antagonistas & inhibidores , ADN de Neoplasias/biosíntesis , Estradiol/metabolismo , Femenino , Humanos , Isoflavonas/metabolismo , Isoflavonas/farmacología , Cinética , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Ratas , Rutina/metabolismo , Rutina/farmacología , Células Tumorales CultivadasRESUMEN
This study describes bronchoalveolar lavage (BAL), histological and immunohistochemical features in a series of 10 patients with cryptogenic organizing pneumonia (COP). The histological diagnosis was performed by transbronchial biopsy in seven cases and by open lung biopsy in three cases. All patients showed a marked increase in lymphocytes and a mild increase in neutrophils and eosinophils in BAL fluid. The number of T-lymphocytes expressing human leucocyte antigen-DR (HLA-DR) surface antigen was increased (p < 0.002). The majority of lymphocytes expressed the CD8 phenotype, so that the CD4/CD8 ratio was markedly decreased. Masson bodies were present in the lung specimens of all patients. Most of the epithelial cells surrounding the Masson bodies were immunoreactive with an anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) monoclonal antibody. The great majority of mononuclear cells in the lung specimens showed immunoreactivity with anti-CD3, anti-CD8 and anti-CD45R0 monoclonal antibodies. In the Masson bodies, spindle cells were immunoreactive with anti-alpha smooth muscle (alpha-sm) actin monoclonal antibody. Glucocorticoid treatment (the therapy of choice in COP) downregulated GM-CSF messenger ribonucleic acid (mRNA) expression in lung epithelial cell lines. These findings indicate that the combination of bronchoalveolar lavage cell profile with histological evidence is a valuable means of corroborating a clinical diagnosis of cryptogenic organizing pneumonia, and that granulocyte/macrophage colony-stimulating factor may be one of the cytokines involved in the pathogenesis.
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Líquido del Lavado Bronquioalveolar/citología , Neumonía en Organización Criptogénica/diagnóstico , Biopsia , Líquido del Lavado Bronquioalveolar/inmunología , Neumonía en Organización Criptogénica/etiología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Humanos , Inmunohistoquímica , Pulmón/patología , Masculino , Persona de Mediana EdadRESUMEN
Glucocorticoid (GC)-induced apoptosis is a well-recognized physiologic regulator of murine T-cell number and function. We have analyzed its mechanisms in human mature T cells, which have been thought to be insensitive until recently. Peripheral blood T cells showed sensitivity to GC-induced apoptosis soon after the proliferative response to a mitogenic stimulation, and were also sensitive to spontaneous (ie, growth factor deprivation-dependent) apoptosis. CD8+ T cells were more sensitive to both forms than CD4+ T cells. Acquisition of sensitivity to GC-induced apoptosis was not associated with any change in number or affinity of GC receptors. Both spontaneous and GC-induced apoptosis were increased by the macromolecular synthesis inhibitors, cycloheximide (CHX) and puromycin. A positive correlation between the degree of protein synthesis inhibition and the extent of apoptosis was observed. Interleukin-2 (IL-2) IL-4, and IL-10 protected (IL-2 > IL-10 > IL-4) T cells from both forms of apoptosis in a dose-dependent manner. Our data suggest that spontaneous and GC-induced apoptosis regulate the human mature T-cell repertoire by acting early after the immune response and differentially affecting T-cell subsets.
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Apoptosis/efectos de los fármacos , Dexametasona/farmacología , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/efectos de los fármacos , Diferenciación Celular , Cicloheximida/farmacología , Humanos , Técnicas In Vitro , Activación de Linfocitos , Inhibidores de la Síntesis de la Proteína/farmacología , Puromicina/farmacología , Linfocitos T/inmunologíaRESUMEN
The possibility that production of some cytokines in the carcinoma microenvironment is associated with the presence and differentiation of cells belonging to the dendritic cell (DC)/Langerhans' cell (LC) lineage was investigated. Immunohistochemical examination showed the presence of intraepithelial LCs (CD1a- and S100-positive cells) in 6 of 10 squamous cell carcinomas and in 8 of 10 adenocarcinomas. Langerhans' cells were mainly located close to lymphoid aggregates. In situ hybridization performed in four cases (three LC positive and one LC negative) of squamous cell carcinoma and in five cases (four LC positive and one LC negative) of adenocarcinoma showed that some mononuclear cells in the interstitium displayed hybridization with granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha), and interleukin 1-beta (IL1 beta) cDNA probes. Only in LC-positive carcinomas did epithelial cells close to lymphoid aggregates display small amounts of GM-CSF and TNF alpha mRNA expression. Immunohistochemical analysis performed in the 20 cases of lung carcinoma showed that epithelial cells in tumors with lymphoid aggregates and LCs were immunoreactive with antihuman GM-CSF monoclonal antibody. Specimens negative for GM-CSF contained very few LCs. Northern blot analysis was used to investigate GM-CSF, TNF alpha, IL1 alpha, and IL1 beta mRNA expression in six human lung carcinoma cell lines. A constitutive expression of TNF alpha mRNA was found in all of them, whereas only three showed a low constitutive expression of GM-CSF mRNA. In the latter three cell lines treatment with phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte (PBL) supernatant (PHA-SUP) upregulated GM-CSF mRNA expression and induced that of IL1 alpha mRNA. Carcinomatous epithelial cells producing small amounts of cytokines could promote the recruitment of cells of DC/LC lineage. Subcellular factors produced by reactive lymphocytes and/or macrophages may influence the production of GM-CSF and IL1 alpha by various epithelia. Up-regulation of this production could favor the arrival and differentiation of DCs and activate LC functions.
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Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Citocinas/fisiología , Células de Langerhans/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Diferenciación Celular , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/fisiología , Humanos , Hibridación in Situ , Interleucina-1/genética , Interleucina-1/fisiología , ARN Mensajero/biosíntesis , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/fisiologíaRESUMEN
The present paper deals with more precise characterization of Langerhans cells (LC) and accompanying lymphocytes in lung LC histiocytosis (LCH) and primary lung peripheral adenocarcinomas using immunohistochemical methods with various kinds of monoclonal antibodies against cell adhesion and activation markers and some cytokines. Tissue specimens were obtained from 4 patients with pulmonary LCH and from 29 patients with primary lung peripheral adenocarcinoma. In florid (exudative and granulomatous) nonfibrotic LCH lesions, LC, particularly those in contact with lymphocytes, were S100, CD1a, MHC Class II, CD11a and c, CD16, and CD54 positive. In this context, LC were CD4+ and CD25+. Lymphocytes around LC were CD3+ with a "memory" phenotype (CD45RO+) and, frequently, CD25+ and HLA-DR+. S100+ and CD1a+ LC were commonly observed in adenocarcinomas subclassified as papillary and as nonmucinous bronchioloalveolar, in both cases mainly where Clara cells and Type II pneumocytes were present. In carcinomas the vast majority of LC were HLA-DR+ and, rarely, weakly CD16+, CD25+, and CD54+. The infiltration of reactive cells in cancer tissue was mainly represented by T lymphocytes (CD3+CD45RO+). These T cells were HLA-DR- and CD25-. The presence of LC was associated with a strong reactivity of epithelial cells with antibodies PE-10 and 439-9B, both recognizing molecules mainly expressed by Type II alveolar cells. Several cells in LCH florid lesions showed immunoreactivity for both IL-1 alpha and beta. Immunostaining for IFN-gamma revealed the presence in the same areas of some positive cells showing lymphoid morphology. No IL-1 or IFN-gamma reactivity was found in adenocarcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)
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Adenocarcinoma/patología , Histiocitosis de Células de Langerhans/patología , Células de Langerhans/patología , Neoplasias Pulmonares/patología , Adenocarcinoma/metabolismo , Anticuerpos Monoclonales , Biopsia , Células Dendríticas/metabolismo , Células Dendríticas/patología , Epitelio/metabolismo , Epitelio/patología , Histiocitosis de Células de Langerhans/metabolismo , Humanos , Inmunohistoquímica , Células de Langerhans/metabolismo , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Linfocitos/metabolismo , Linfocitos/patología , Fenotipo , Coloración y Etiquetado/métodosRESUMEN
The oral cavity, and particularly the gingival mucosa, is continuously exposed to numerous food and bacterial plaque antigens, though evident immunologic reactions are uncommon. It is therefore possible that the mucosal associated lymphoid tissue (MALT) of this region is preferentially biased towards unresponsiveness, rather than immune cell activation. The distribution and phenotype of immune cells in normal human gingiva were examined. Their distribution varied, and high and low cellularity areas could be distinguished in the same specimen. The number of CD3 positive (CD3+) T lymphocytes was more than thrice higher in a high cellularity area. In both types of area, intraepithelial T lymphocytes were not activated. Moreover, they showed chromatin condensation and cell shrinkage characteristic of apoptosis. In the stroma of high cellularity areas, foci of cell activation and numerous B cells were present, suggesting a localized active immune response. The vast majority of intraepithelial and stromal T lymphocytes expressed the "memory" CD45RO+ phenotype. The absence of an immune response within the epithelium and the localized response in the stroma (probably due to the binding of memory T cells to antigens in a low affinity, cross-reactive fashion) may be a part of a protective mechanism against indiscriminate stimulation by a multitude of external antigens.
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Antígenos de Superficie/análisis , Linfocitos B/inmunología , Encía/inmunología , Linfocitos T/inmunología , Adulto , Anticuerpos Monoclonales , Antígenos Bacterianos/inmunología , Linfocitos B/citología , Células del Tejido Conectivo , Células Dendríticas/citología , Células Epiteliales , Hipersensibilidad a los Alimentos/inmunología , Encía/citología , Humanos , Inmunohistoquímica , Inmunofenotipificación , Células de Langerhans/citología , Recuento de Leucocitos , Macrófagos/citología , Linfocitos T/citología , Linfocitos T Citotóxicos/citología , Linfocitos T Colaboradores-Inductores/citologíaRESUMEN
Interleukin 1 (IL-1) and tumor necrosis factor (TNF) have recently been shown to be involved in bone resorption, and because macrophages constitute a significant part of human periapical granulomas, it is reasonable to suspect that they may secrete IL-1 and TNF. The purpose of our investigation was to detect and characterize IL-1 beta- and TNF-alpha-producing cells in human periapical granulomas. Fresh tissue samples obtained during surgery from 10 patients with previously untreated teeth and histologically established periapical granulomas were studied with light and electron microscopy and with immunohistochemical analysis with monoclonal antibodies against IL-1 beta and TNF-alpha. There were very few IL-1 beta + and TNF-alpha + cells present in periapical granulomas, and the positive cells had monocyte/macrophage morphology. The IL-1 beta + cells were located mainly in areas of active exudation and were surrounded by and/or were in close contact with lymphoid cells, whereas TNF-alpha + cells were scattered and in contact with or near other inflammatory cells at the periphery of active granulation tissue. This suggests that the IL-1 beta + cells may act in a paracrine manner to activate lymphoid cells. The ultrastructural findings showed that only some macrophages are adapted to extracellular secretion rather than phagocytosis. These modified macrophages could be the major producers of interleukins in tissues. Occasionally, they have plasmacytic or plasmacytoid features resembling the so-called "plasmacytoid monocytes". Only a minor fraction of the monocytes/macrophages (representing about 40% of the inflammatory cells) is in an active cytokine-producing state.(ABSTRACT TRUNCATED AT 250 WORDS)
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Resorción Ósea/inmunología , Interleucina-1/biosíntesis , Granuloma Periapical/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Humanos , Inmunohistoquímica , Macrófagos/metabolismo , Macrófagos/ultraestructura , Monocitos/metabolismo , Monocitos/ultraestructura , Granuloma Periapical/metabolismoRESUMEN
Monoclonal antibodies (MAbs) COL-4 and COL-12, to the carcinoembryonic antigen (CEA), and B72.3, CC-49, CC-83, to the tumor-associated glycoprotein 72 (TAG-72), were used to study the expression of distinct epitopes of the two molecules in 71 cases of lung carcinoma of differing histotype. These MAbs reacted with the majority of adenocarcinomas by immunoperoxidase on tissue sections, but demonstrated a more restricted reactivity with squamous carcinomas. MAb CC-49 detected the highest percentages of adenocarcinoma cells while the B72.3 epitope was expressed more in squamous carcinoma cells. No significant reactivity with any of these MAbs was observed in small cell carcinomas. The expression of the CEA and TAG-72 epitopes in non-small cell lung cancers was highly heterogeneous: a distinct epitopes in non-small cell lung cancers was highly heterogeneous: a distinct epitope could be expressed by the majority of cells, whereas another of the same antigenic molecule was either poorly or not expressed. In adenocarcinomas, mixtures of anti-CEA, anti-TAG-72, and anti-(TAG-72 plus CEA) MAbs resulted in additive reactivity with an increase of the immunopositive tumors and of the percentages of immunostained cells. This was particularly evident for the anti-(TAG-72 plus CEA) mixture. In squamous cell carcinomas the increase was modest and was mainly related to anti-TAG-72 reactivity. These studies suggest variability in the antigenic structure of tumor-associated antigens expressed by carcinomas and indicate that anti-(TAG-72 plus CEA) mixtures may represent an immunological adjunct for clinical application in adenocarcinoma patients. On the other hand, TAG-72 should be considered a better target antigen, as compared to CEA, in the detection of squamous cell carcinomas.
Asunto(s)
Adenocarcinoma/inmunología , Anticuerpos Monoclonales/inmunología , Antígeno Carcinoembrionario/inmunología , Carcinoma de Células Pequeñas/inmunología , Carcinoma de Células Escamosas/inmunología , Glicoproteínas/inmunología , Neoplasias Pulmonares/inmunología , Adenocarcinoma/metabolismo , Antígenos de Neoplasias/inmunología , Carcinoma de Células Pequeñas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Epítopos/inmunología , Fijadores , Formaldehído , Congelación , Glicoproteínas/metabolismo , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/inmunología , Proteínas de Neoplasias/metabolismo , ParafinaRESUMEN
In this study, the expression of the alpha 6/beta 4 integrin complex was analyzed in human lung carcinomas both in vitro and in vivo, using two monoclonal antibodies which recognize the integrin subunits alpha 6 (Mab 135-13C) and beta 4 (Mab 439-9B). Immunoprecipitation patterns obtained from established human lung carcinoma cell lines demonstrated that the alpha 6 and the beta 4 subunits were differentially expressed in carcinomas of different types. The alpha 6 subunit was expressed in all the cell lines tested (squamous cell carcinoma A431, adenocarcinoma A549, large cell carcinoma DG3, and small cell carcinoma AE2). The beta 4 subunit was expressed in non-small cell cancer lines but was not detectable in the small cell cancer line tested. Using a quantitative two-site assay, we measured the concentration of the alpha 6/beta 4 integrin in matched biopsies from primary lung tumors and from normal lung. These studies confirmed that the complex was differentially expressed in non-small versus small cell lung cancers and that it was also detectable in lysates from normal lung at low levels. The highest levels of alpha 6/beta 4 were found in moderately differentiated squamous cell carcinomas. By immunohistochemistry, the beta 4 subunit was detectable in all the squamous cell carcinoma and adenocarcinomas tested (a total of 59), but not in 10 small cell cancers. The patterns of immunoreactivity were consistent with the expected distribution of membrane glycoproteins and, in some squamous cell carcinomas, were suggestive of the localization displayed by molecules involved in carcinoma-stroma interaction. Immunohistochemical staining indicated that beta 4 was also expressed in specific types of nonrespiratory pulmonary epithelial cells.
Asunto(s)
Anticuerpos Monoclonales , Integrinas/análisis , Adenocarcinoma/química , Carcinoma de Células Escamosas/química , Línea Celular , Humanos , Integrinas/inmunología , Neoplasias Pulmonares/química , Pruebas de PrecipitinaRESUMEN
The anesthesist is very often asked to manage severe painful syndromes in patients suffering widespread malignant tumours. So often, the extent of neoplastic diffusion is such that common technics for analgesic block cannot be performed. The chemiolysis of the hypophysis-according to Moricca-performed primarily for therapeutic purposes has also shown a powerful analgesic effect.