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Results for “Local Lymph Node Assay”

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PubMed1997

Expression of p53, glutathione S-transferase-pi, and Bcl-2 proteins and benefit from adjuvant radiotherapy in breast cancer.

BACKGROUND: In clinical breast cancer research, the utility of certain biomarkers as predictors of response to surgery, chemotherapy, or hormonal therapy has been studied intensively. Much less research has been done on the relevance of biologic predictors of response to radiotherapy, which represents an effective local-regional treatment for breast cancer. PURPOSE: The utility of biomarkers involved in DNA damage repair (p53 protein), control of programmed cell death (p53 and Bcl-2 proteins), and cellular detoxification (glutathione S-transferase-pi [GST-pi] enzyme) in predicting local breast cancer recurrence was analyzed retrospectively in two cohorts of breast cancer patients. These patients had had no detectable metastases in the axillary lymph nodes (i.e., node-negative) or in distant sites and had had similar distributions of clinicopathologic and biologic prognostic features. They had been treated by conservative surgery alone (139 case patients) or by conservative surgery followed by adjuvant radiotherapy (496 case patients) during the period from 1984 through 1990. METHODS: The expression of the p53, GST-pi, and Bcl-2 proteins in the specimens of primary breast tumor obtained from these patients was determined by use of immunohistochemistry; cell proliferation activity and levels of steroid receptors were determined by use of a [3H]thymidine-labeling index assay and the dextran-coated charcoal technique, respectively. The median time of follow-up of patients was 6 years. In the analyses of patient outcomes, only local failures that presented as first events were considered. RESULTS: After surgery alone, the risk of local recurrence at 6 years was higher for patients with tumors exhibiting elevated levels of p53 and GST-pi protein expression than for patients with low levels (hazard ratio [HR] = 3.1, 95% confidence interval [CI] = 1.3-7.7, two-sided P = .012; HR = 2.7, 95% CI = 1.1-6.4, two-sided P = .026, respectively). Weak or no observable expression of Bcl-2 protein was only suggestive of a higher frequency of local failures. Adjustment for patient age, tumor size, cell proliferation, and estrogen receptor status did not change these findings. Conversely, in the series of patients given conservative surgery followed by radiotherapy, there was no difference in local tumor recurrence between patients with tumors expressing or not expressing each of the three markers. CONCLUSIONS: Our study provides indirect evidence of a benefit from radiation therapy in preventing local breast cancer relapse, particularly among node-negative patients with tumors that express elevated levels of the p53 or GST-pi proteins or that express little or no Bcl-2 protein.

Biomarkers, Tumor↗

PubMed1999

Progressive increase in telomerase activity from benign melanocytic conditions to malignant melanoma.

The expression of telomerase activity and the in situ localization of the human telomerase RNA component (hTR) in melanocytic skin lesions was evaluated in specimens from sixty-three patients. Specimens of melanocytic nevi, primary melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight patients, whereas metastasized lymph nodes were obtained from five patients. Telomerase activity was determined in these specimens by using a Polymerase Chain Reaction-based assay (TRAP). High relative mean telomerase activity levels were detected in metastatic melanoma (subcutaneous metastases = 54.5, lymph node metastases = 56.5). Much lower levels were detected in primary melanomas, which increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark III = 1.1, and Clark IV = 1.9). Twenty-six formalin-fixed, paraffin-embedded melanocytic lesions were sectioned and analyzed for telomerase RNA with a radioactive in situ hybridization assay. In situ hybridization studies with a probe to the template RNA component of telomerase confirmed that expression was almost exclusively confined to tumor cells and not infiltrating lymphocytes. These results indicate that levels of telomerase activity and telomerase RNA in melanocytic lesions correlate well with clinical stage and could potentially assist in the diagnosis of borderline lesions.

Humans↗

PubMed2000

Values and limitations of 18F-fluorodeoxyglucose-positron-emission tomography with preoperative evaluation of patients with pancreatic masses.

The aim of this study was to determine the value and limitations of 18F-fluorodeoxyglucose (FDG)-position-emission tomography (PET) for differentiating benign and malignant pancreatic disease and for staging malignant disease. One hundred fifty-nine patients with 89 malignant and 70 benign pancreatic lesions all received PET, computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) before pancreatic surgery. The original reports were compared for all patients (group I; N = 159), for a subgroup that neither had fasting plasma glucose levels > or =130 mg/dL or known elevated levels of C-reactive protein ([CRP], group II; n = 123), and for the remaining patients (group III; n = 36). For group I, accuracy values (areas under receiver operating characteristic [ROC] curves) for differentiation of benign/malignant masses were 0.86 (PET), 0.93 (ERCP), 0.82 (CT), and 0.95 for ERCP + PET (N = 159). For group II, ROC areas increased to 0.92 (PET), 0.94 (p < 0.05; n = 123) (ERCP), 0.82 (CT), 0.97 (p < 0.05; n = 123) (ERCP + PET). The results for group III were 0.71 (PET), 0.81 (CT), and 0.93 (ERCP); (n = 36). With 54 patients of group II that either had contradictory or indeterminate/technically unsuccessful CT/ERCP, PET was correct in 43 patients (84%). Sensitivity/specificity for lymph node staging was 49%/63%, respectively. For patients with hepatic metastasis, PET was 70% sensitive and 95% specific, missing some metastasis that were <1 cm. PET detected peritoneal metastasis in 25% of patients, missing poorly localized microscopic spread. For selected patients who have indeterminate pancreatic masses but no hyperglycemia or serologic evidence of active inflammation, FDG-PET is an independent functional assay that significantly adds to the diagnostic accuracy of ERCP and CT in the differentiation of benign and malignant pancreatic disease. PET can reliably detect hepatic, peritoneal, and other distant metastases that are > or =1 cm.

Area Under Curve↗

PubMed1982

[Malignant ovarian tumors in childhood].

Malignant ovarian tumors only account for 3 per cent of all malignancies under 15 years of age, and more than two third of them are of germ cell origin. Abdominal mass and/or pains are the usual revealing symptoms and abnormal sexual prematurity is infrequently encountered. Diagnostic ultrasonography is currently the most useful imaging investigation. Alpha-foeto-protein (alpha-FP) serum determination is mandatory before surgery to indicate the presence of endodermal sinus tumor cells. Surgical procedure is in childhood usually restricted to unilateral salpingo-oophorectomy, if allowed by tumoral spreading which is carefully searched in the abdominal cavity. Thus will be defined, along with the post-operative lymphangiography, the extension of the tumor, according to the staging system of Wollner (Memorial Hospital NY) more than the FIGO. Malignant teratomas are the most frequent malignant germ cell ovarian tumors in young females. They may realize pure or mixed pathological types of immature teratoma, embryonal carcinoma, endodermal sinus tumor and very seldom choriocarcinoma. Serial assays of serum alpha-FP are of utmost value to follow therapeutic progress or detect recurrences. Since new sequential multidrug protocol including, vincristine, actinomycin D, cyclophosphamide, adriamycin, méthotrexate and cis-platinum, protracted survivals are to be expected in a higher number of patients with localized stages and even in some with advanced disease. Value of extended pelvi-abdominal and/or lymph node radiotherapy is still under evaluation. Ovarian dysgerminomas are radiosensitive tumors in which chemotherapy is as a rule not indicated. Relapses may be most often prevented by a prophylactic irradiation of iliac ipsilateral, lumboaortic, mediastinal and supraclavicular nodes. Among functional ovarian tumors, mainly granulosa cell types with isosexual precocity, malignant tumors are so rarely encountered that no complementary treatment has to be performed after a complete resection. Cystadenocarcinoma or borderline ovarian epithelial tumors occur after puberty and require the same treatment as in adult though keeping a conservative view. Ovarian deposits of Burkitt's tumor may account in some exposed african areas for most ovarians malignancies in childhood. Gonadoblastomas with both stromal and germ cell elements are exclusively to be found in dysgenetic gonads.

Adolescent↗

PubMed2004

The level of virus-specific T-cell and macrophage recruitment in porcine reproductive and respiratory syndrome virus infection in pigs is independent of virus load.

Porcine reproductive and respiratory syndrome virus (PRRSV) is the most important infectious disease agent of pigs worldwide, causing reproductive failure in pregnant sows and respiratory problems in nursing and growing pigs. PRRSV infection is characterized by a prolonged viremia of 30 or more days and an extended persistent infection of lymphoid tissues. To better understand the immunological basis for prolonged acute and persistent PRRSV infection, we have examined the cell-mediated immune (CMI) response throughout the course of infection and compared the results to the local distribution and abundance of PRRSV in infected tissues. PRRSV-specific T cells, enumerated by gamma interferon enzyme-linked immunospot assay, did not appear until 2 weeks after PRRSV inoculation, and their abundance exhibited substantial variation over time and among animals. In all cases the T-cell response was transient. High levels of viral RNA were present in lymphoid tissues of all animals in the acute phase of infection. Viral loads were decreased 1,000-fold or more in persistent infections, with the primary sites of persistence being tonsil, sternal lymph node, and inguinal lymph node. The abundance of virus-specific T cells in either acutely or persistently infected animals was highly variable and showed no correlation to the level of virus in lymphoid tissues. No significant difference in antigen-specific T-cell abundance was observed in secondary lymphoid tissues in either acute or persistent infection except for tonsil, in which the number of responding cells was extremely low. CD4(+)- and CD8(+)-T-cell frequencies did not change after PRRSV infection, though a decrease in gammadelta T cells was observed. Macrophages, the permissive cell type for PRRSV, were present in various levels in all tissue preparations and were not in proportion to local virus load. These findings indicate that a weak CMI response contributes to prolonged PRRSV infection and suggests that PRRSV suppresses T-cell recognition of infected macrophages. Thus, the slow but eventual resolution of PRRSV infection may be dependent on limiting permissive macrophages and on innate immune factors.

Animals↗

PubMed2004

Detection of cancer cells in the axillary drainage using RT-PCR after operations for breast cancer.

The object of this study was to examine whether MUC-1 can be detected in the axillary lymphatic drainage of patients who have undergone conservative surgery for breast cancer and to assess the correlations between the presence of MUC-1 and prognostic factors in breast cancer. Sixty-eight women with invasive ductal carcinoma of the breast underwent wide local excision and axillary lymph node dissection. Axillary drains were inserted in all these cases, and the presence of MUC-1 and beta-actin was evaluated by RT-PCR in the lymphatic fluid collected after the operation. Prognostic factors included tumour size and grade, vascular and lymphatic invasion, clearance margins of the resected specimens and status of the axillary lymph nodes. RT-PCR assays for MUC-1 in the axillary fluid were positive in 17 patients (25%). The presence of MUC-1 was associated with increased tumour size and showed a positive correlation with axillary lymph node metastases and incomplete resection of the tumour. RT-PCR can disclose cancer cells in the axillary fluid after conservative surgery for breast cancer. The presence of MUC-1 in the axillary drainage may be associated with poor prognostic features, and its detection may have implications for therapy as it suggests that re-excision should be considered.

Axilla↗

PubMed2000

Interleukin-6 is produced during both murine and avian Eimeria infections.

The production of interleukin-6 (IL-6) during Eimeria infection was investigated in an attempt to gain a better understanding of the role of this multi-functional cytokine in resistance to this parasite. IL-6 production was measured in both chickens, in which the disease is of economic importance, and the better-characterised murine model system. Systemic and local IL-6 production in mice during E. vermiformis infection was investigated, in the relatively resistant BALB/c strain, and the relatively susceptible C57 BL/6 strain, using a murine IL-6 ELISA and the 7TD1 assay. Enhanced systemic production of IL-6 in serum was seen in infected BALB/c mice when compared to C57 BL/6 mice. This difference was also reflected in the draining lymph node of the site of infection, assessed by testing supernatants from stimulated mesenteric lymph node cells taken from infected mice at different times post-infection. Production of chicken IL-6-like factor activity was investigated using a murine IL-6 7TD1 bioassay. The presence of substantial quantities of IL-6-like factor activity was detected in serum taken from some chickens infected with E. tenella during the course of primary infection and, in a separate experiment, during the first few hours post-infection, a time when the pro-inflammatory capacity of IL-6 would influence the developing immune response. These results suggest that IL-6 is also important in the induction of immune effector responses to Eimeria infections in the chicken.

Animals↗

PubMedDate not supplied

Distribution of factor VIII mRNA and antigen in human liver and other tissues.

The cellular site of synthesis of factor VIII (FVIII:C; anti-haemophilic factor) has long been sought. Previous studies suggested the liver as a major site of synthesis, but extrahepatic sources such as spleen and lung have been implicated. Using an immunoradiometric assay (IRMA), we recently localized factor VIII antigen (FVIII:Ag, formerly FVIII:CAg), to whole perfused guinea pig liver and spleen, and to isolated hepatocytes, with lesser or trace amounts in other tissues. Using an immunohistological technique, Stel et al. detected FVIII:Ag in normal human liver sinusoidal endothelial cells, while Exner et al. detected FVIII:Ag by IRMA in extracts of human lymph nodes, lung, liver and spleen. The localization of antigen in tissues does not, however, distinguish sites of factor VIII synthesis from those of storage, and such experiments are subject to misinterpretation due to entrapment of plasma factor VIII in tissues. The recent cloning of the human factor VIII gene provides hybridization probes for the detection of factor VIII messenger RNA in cells, thus directly determining sites of synthesis. During complementary DNA cloning, we detected factor VIII mRNA in liver, and it has been localized by others in liver and placenta and in liver and kidney. In the present study, we detected factor VIII mRNA in isolated human hepatocytes, in spleen and in numerous tissues including lymph nodes and kidney, but not in white blood cells or cultured endothelial cells. We also found that the factor VIII, factor VII, factor IX and protein C antigens in liver are predominantly localized in hepatocytes, while very little von Willebrand factor antigen (vWF:Ag, formerly FVIIIR Ag) is detectable in this organ.

Factor IX↗

PubMed2006

Tumor-specific CD8+ T cell reactivity in the sentinel lymph node of GM-CSF-treated stage I melanoma patients is associated with high myeloid dendritic cell content.

PURPOSE: Impaired immune functions in the sentinel lymph node (SLN) may facilitate early metastatic events during melanoma development. Local potentiation of tumor-specific T cell reactivity may be a valuable adjuvant treatment option. EXPERIMENTAL DESIGN: We examined the effect of locally administered granulocyte/macrophage-colony stimulating factor (GM-CSF) on the frequency of tumor-specific CD8+ T cells in the SLN and blood of patients with stage I melanoma. Twelve patients were randomly assigned to preoperative local administration of either recombinant human GM-CSF or NaCl 0.9%. CD8+ T cells from SLN and peripheral blood were tested for reactivity in an IFNgamma ELISPOT assay against the full-length MART-1 antigen and a number of HLA-A1, HLA-A2, and HLA-A3-restricted epitopes derived from a range of melanoma-associated antigens. RESULTS: Melanoma-specific CD8+ T cell response rates in the SLN were one of six for the control group and four of six for the GM-CSF-administered group. Only one patient had detectable tumor-specific CD8+ T cells in the blood, but at lower frequencies than in the SLN. All patients with detectable tumor-specific CD8+ T cells had a percentage of CD1a+ SLN-dendritic cells (DC) above the median (i.e., 0.33%). This association between above median CD1a+ SLN-DC frequencies and tumor antigen-specific CD8+ T cell reactivity was significant in a two-sided Fisher's exact test (P = 0.015). CONCLUSIONS: Locally primed antitumor T cell responses in the SLN are detectable as early as stage I of melanoma development and may be enhanced by GM-CSF-induced increases in SLN-DC frequencies.

Adult↗

PubMed2000

Analysis of in vivo regulatory properties of T cells activated in vitro by TGFbeta2-treated antigen presenting cells.

PURPOSE: To determine whether naive T cells activated in vitro by antigen-pulsed, transforming growth factor(beta) (TGFbeta)-treated antigen presenting cells (APCs) acquire the capacity to suppress the induction and expression of delayed hypersensitivity in vivo. METHODS: Naive ovalbumin (OVA)specific T cells from DO 11.10 Tcr transgenic mice were stimulated in vitro with OVA-pulsed TGF(beta2)-treated APCs. The cultured cells were harvested and assayed for in vitro production of mature TGFbeta. Similar cells were coinjected with primed OVA-specific BALB/c T cells plus OVA-pulsed APCs into ear pinnae of normal BALB/c mice (assay for delayed hypersensitivity expression) or coinjected with OVA-pulsed APCs into footpads of naive DO11.10 mice whose draining lymph node cells were harvested 4 days later and assayed in vitro for capacity to secrete interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) when stimulated with OVA (assay for induction of delayed hypersensitivity). RESULTS: DO11.10 T cells activated in vitro by OVA-pulsed TGFbeta2-treated APCs secreted large amounts of mature TGFbeta and suppressed the expression of delayed hypersensitivity in a local adoptive transfer assay. Suppression was reversed in the presence of neutralizing anti-TGFbeta antibodies. In addition, in vitro generated regulatory T cells influenced naive T cells in DO11.10 mice that were responding to an initial immunization with OVA to secrete IL-4, rather than IFN-gamma. This influence was independent of TGFbeta. CONCLUSIONS: OVA-pulsed APCs, pretreated in vitro with TGF(beta)2, activate DO11.10 T cells in a manner that endows the responding cells with the capacity to suppress the induction and then the expression of delayed hypersensitivity in vivo. In certain ways, these properties of in vitro-activated DO11.10 T cells resemble the properties of afferent and efferent regulatory T cells typically found in the spleens of animals with anterior chamber-associated immune deviation.

Animals↗

PubMed1998

[Detection of disseminated carcinoma cells in bone marrow and peripheral blood in primary breast cancer with RT/PCR of parathyroid hormone-related protein (PTHrP)].

The analysis of tissue specific gene expression by reverse transcription based RT/PCR methods is currently evaluated as a method for the detection of tumor cell dissemination in patients with cancer. Breast cancer tissues express PTHrP and the level of PTHrP expression in the primary tumor correlates with the incidence of metastases in the bone. We applied a RT/PCR assay of PTHrP to detect tumor cells in the mononuclear cell fraction of peripheral blood (pb) and bone marrow (bm) of patients with newly diagnosed breast cancer. PTHrP positivity was found in 18/67 pb and 20/71 bm samples. In a median follow up of 23 months there were 7 metastatic relapses (4 osseous, 2 hepatic, 1 pulmonary) and 9 local relapses in patients with primary lymph node positive breast cancer. The hepatic and pulmonary relapses had been both PTHrP-PCR negative in pb and in bm. Of the 4 patients with metastatic relapses to the bone the samples of bm had been initially negative in all cases, the pb had been positive in 2 cases. Of the 9 patients with local recurrences the pb alone had been positive in 4 patients, 5 patients had been negative in both the pb and the bm. During the period of observation there was no local and metastatic relapse detectable in the group of patients with primary lymph node negative breast cancer. In summary the increased risk for local or systemic relapse would have been predictable by RT/PCR of PTHrP alone in pb in 4 of the 9 local and in 2 of the 7 early metastatic relapses. Further follow-up of the patient cohort analysed is needed to assess the value of the RT/PCR of PTHrP as a prognostic and predictive marker in patients with breast cancer.

Adult↗

PubMed1998

[Papillary and follicular cancers of the thyroid].

MANAGEMENT STRATEGIES: Management of papillary and follicular cancer of the thyroid varies somewhat between centers because of the generally good prognosis and the absence of well-controlled therapeutic trials. The internationally recognized TNM system is widely used to modulate treatment and follow-up to the individual situation. PRIMARY TREATMENT: Surgery is indicated in well-differentiated thyroid cancer. Total thyroidectomy is required for clinically patent tumors (> or = 1 cm) and small tumors (< 1 cm) recognized prior to surgery. For small tumors found at histology examination, reoperation is discussed in terms of prognosis. Post-operative 131-iodine is indicated when surgical resection is incomplete or in case of unfavorable prognosis. External radiotherapy is currently reserved for exceptional cases with unremoved tumoral tissue unresponsive to 131-iodine. FOLLOW-UP: All operated patients are given L-thyroxine to achieve euthyroidism and low TSH levels (< 0.1 microU/ml). Early detection of relapse is based on combined thyroglobulin assay and whole body 131-iodine scintigraphy. Both are performed during the first year of follow-up after a period of thyroid hormone withdrawal. Human recombinant TSH will soon be available allowing selection of patients with a detectable thyroglobulin level after stimulation; these patients should have a 131-iodine scintigram. If thyroglobulin remains undetectable during L-thyroxine treatment, an annual dosage is indicated and other exams are unwarranted. RELAPSE: Surgery is indicated in case of small areas of active recurrent tumoral tissue in a cervical location. If a high-sensitivity scintigram does not show iodine uptake, the surgical procedure is completed by radiotherapy or possibly chemotherapy with doxorubicin. Small recurrent tumors in other areas respond to 131-iodine (3.7 GBq). Surgery, 131-iodine and radiotherapy are usually indicated for large ectopic recurrences. Chemotherapy is ineffective. CURRENT PROTOCOLS: Standard primary therapy generally provides cure and most patients are followed by annual thyroglobulin and TSH assays. Other explorations beginning with a whole-body 131-scintigram may be indicated in selected patients.

Carcinoma, Papillary, Follicular↗

PubMed1993

Identification and localization of a novel cathepsin S-like proteinase in guinea pig spermatozoa.

Guinea pig spermatozoa were found to contain a novel cysteine proteinase that most closely resembled lysosomal cathepsin S. The responsible enzyme was shown to have an acrosomal localization. Like the cathepsin S of lymphocyte-rich tissues, e.g., lymph nodes and spleen, the spermatozoal enzyme digested protein substrates such as hemoglobin and Azocoll optimally at about pH 3.5 in the presence of pepstatin. No appreciable action was manifested in the range of pH 5-6 on protein substrates nor on the 7-(4-methyl)coumarylamide (NMec) derivatives of peptides commonly employed for the fluorometric assay of cathepsins B (benzyloxycarbonyl (Z)-Arg-Arg-NMec), H (Arg-NMec), and L (Z-Phe-Arg-NMec). Like spleen cathepsin S, the sperm enzyme selectively hydrolyzed Z-Phe-Arg-NMec, but its activity was uncharacteristically limited to a pH range of 3.0-3.5, where it displayed a typical high sensitivity to sulfhydryl reagents (HgCl2, mersalyl acid, iodoacetate), leupeptin, Z-Phe-Phe-CHN2, and L-trans-epoxysuccinylleucylamido(3-methyl)butane. Gossypol (a male antifertility agent) was also inhibitory. Inhibition by the mercurial sulfhydryl reagents was completely reversible with dithiothreitol. Pepstatin, a potent inhibitor of aspartic proteinases, and serine proteinase inhibitors (phenylmethylsulfonyl fluoride, benzamidine) were ineffective. Other properties displayed by the sperm extract that were uniquely characteristic of cathepsin S included stability under alkaline conditions, and a greater rate of hydrolysis when the P2-phenylalanine of the assay substrate was replaced by two aliphatic residues, as in Z-Leu-Leu-Arg-NMec.

Acrosome↗

PubMed1992

Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues.

The concentrations of urinary type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), and PAI-2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues. Levels of u-PA, PAI-1 and PAI-2 were higher in cancer than in control tissues. PAI-1 levels were higher together with the progression of cancer however there were no differences in u-PA or PAI-2 levels. Tumors with higher PAI-1 and lower PAI-2 levels tend to metastasize to remote lymph nodes. When the numbers of involved lymph nodes were analyzed, tumors with the large number of metastatic lymph nodes showed higher PAI-1 and lower PAI-2 level. No difference was shown in u-PA levels among these groups. These tendencies were more significant in patients with progressed gastric cancer. These results suggest that tumor with higher PAI-2 levels tend to localize or have less tendency to metastasize to lymph nodes. On the other hand PAI-1 was generally higher in tumor with invasion into nearby tissue or with nodal metastasis.

Enzyme-Linked Immunosorbent Assay↗

PubMed2003

Increased tumour necrosis factor alpha production in mesenteric lymph nodes of cirrhotic patients with ascites.

BACKGROUND: Cytokines produced in mesenteric lymph nodes of cirrhotic rats with bacterial translocation may participate in circulatory alterations of cirrhosis. AIM: To investigate whether cirrhotic patients present an increased local generation of cytokines in mesenteric lymph nodes. METHODS: Mesenteric lymph nodes from 26 cirrhotic and 10 control patients were assessed for tumour necrosis factor alpha (TNF) and interleukin 6 mRNA and protein expression by competitive reverse transcription-polymerase chain reaction, and by enzyme immunoassay and immunohistochemistry, respectively. RESULTS: Interleukin 6 levels were not different between cirrhotics and controls. Protein and mRNA TNF levels in mesenteric lymph nodes from cirrhotics were higher than in controls (p<0.05). Tissue expression of TNF by immunohistochemistry was more abundant in cirrhotics. Ascitic patients showed higher TNF levels (47 (34-54) pg/mg protein) than patients without ascites (18 (17-25) pg/mg protein) (p<0.001). Elevated TNF levels (>28 pg/mg protein) in cirrhotics were associated with a higher Child-Pugh score, the antecedent of ascites, a lower prothrombin rate, and higher bilirubin and blood TNF levels. The strongest association, confirmed by multivariate analysis, was with the presence of ascites (p<0.001). Bacterial infections after transplantation, mainly by enteric bacteria, were only detected in patients with high TNF levels in mesenteric lymph nodes (33% of patients; p=0.05). CONCLUSION: Patients with advanced liver cirrhosis, and especially with ascites, have increased local production of TNF in mesenteric lymph nodes that, in common with experimental cirrhosis, may also be induced by bacterial translocation.

Ascites↗

PubMed2001

Minimal residual disease in non-small-cell lung cancer.

Early metastatic relapse after complete resection (R0) of apparently localized primary tumors is frequent in patients with non-small-cell lung cancer (NSCLC). This observation indicates an occult tumor cell dissemination already present at the time of primary surgery but undetectable by current tumor staging methods. During the past 10 years ultrasensitive immunohisto-/-cytochemical and molecular assays have been developed that are able to detect single tumor cells and small tumor cell clusters present in lymph nodes classified as tumor-free by conventional histopathologic analysis, bone marrow, or peripheral blood. Here we present an overview of the incidence and prognostic impact of such early disseminated tumor cells in patients with NSCLC.

Carcinoma, Non-Small-Cell Lung↗

PubMed1997

Contrasting immunopathogenic properties of highly homologous peptides from rat and human thyroglobulin.

The current lack of amino acid sequence data for mouse thyroglobulin (Tg) necessitates mapping of pathogenic T-cell epitopes on heterologous Tg in mouse experimental autoimmune thyroiditis (EAT). A prevailing assumption has been that epitopes sharing a high degree of amino acid homology among heterologous Tg are likely to exhibit the same immunopathogenic properties in the same host. In this report, we have examined this concept while working with the 18-mer rat(r)Tg(2695-13) peptide that was previously shown to elicit 'A'-restricted T cells and EAT in SJL mice. A major immunopathogenic T-cell epitope was localized within the 12-mer rTg(2695-06). It was found that the human 12-mer homologue that carries two Ser substitutions at Glu2703 and Thr2704 exhibited contrasting properties: it failed to activate Th1 cells in lymphokine and proliferation assays; it did not cross-react with rTg(2695-06) at the T-cell level; and it induced only focal thyroiditis following adoptive transfer of specific lymph node cells. These data highlight the caveat involved in extrapolating results of pathogenic T-cell epitope mapping across heterologous Tgs, even when such epitopes share a high degree of amino acid homology.

Amino Acid Sequence↗

PubMed2001

Annual changes in the clinical features of prostatic adenocarcinoma in Taiwan.

OBJECTIVE: To determine, using a clinical and pathological database, the annual changes in the characteristics of adenocarcinoma of the prostate diagnosed in consecutive men in Taiwan. PATIENTS AND METHODS: All prostatic adenocarcinomas newly diagnosed between 1991 and 1999 in our institution were analysed. Using logistic regression for dichotomous variables, the annual trends were assessed for changes in the percentage of T1c disease, incidental carcinoma, clinically localized disease and Gleason grade 4/5 cancers. The annual trends for changes in the pathological features of disease in patients treated by radical prostatectomy were also analysed. RESULTS: The study included 694 patients; the median age at diagnosis increased significantly (P = 0.004) and there was a significant increase in clinical T1c disease (relative risk, RR, 1.142, P = 0.022). There were also significant decreases in incidental carcinomas (RR 0.789, P < 0.001), patients with a serum prostate-specific antigen (PSA) level of > 20 ng/mL (RR 0.848, P < 0.001) and with Gleason grade 4/5 tumours (RR 0.919, P = 0.005). There was no significant change in the percentage of clinically localized disease. Radical prostatectomy was undertaken in 179 men; the annual incidence of lymph node metastases decreased significantly (P = 0.035) and there was a significant 19% increase in the RR of having organ-confined disease (pT1-2N0M0) and a 19% decrease in Gleason grade 4/5 tumours. CONCLUSIONS: These results may reflect the annual trends of prostate cancer in Taiwan in the period for which the PSA assay became available. The increasing application of PSA testing was associated with a significant increase in clinical T1c disease and decrease in incidental carcinoma. There was also a significant trend towards less aggressive cancers. Despite the dramatic increase in the annual detection rate, tumours were not detected at an earlier stage. However, for patients treated with radical prostatectomy, there was a significant change to earlier stage disease and fewer de-differentiated cancers.

Adenocarcinoma↗