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Results for “Local Lymph Node Assay”

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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↗

PubMed1995

Antibody-forming cell response to virus challenge in mice immunized with DNA encoding the influenza virus hemagglutinin.

Immunization of mice with DNA encoding the influenza virus hemagglutinin (HA) affords complete protection against lethal influenza virus infection and the means to investigate the mechanisms of B-cell responsiveness to virus challenge. Using a single-cell enzyme-linked immunospot assay, we sought to determine the localization of HA-specific antibody-forming cells (AFCs) during the development of humoral immunity in mice given HA DNA vaccine by gene gun. At 33 days postvaccination, populations of AFCs were maintained in the spleen and bone marrow. In response to lethal challenge with influenza virus, the AFCs became localized at the site of antigenic challenge, i.e., within the draining lymph nodes of the lung compartment. Immunoglobulin G (IgG)- and IgA-producing AFCs were detected in lymph nodes of the upper and lower respiratory tracts, underscoring their importance in clearing virus from the lungs. Response to challenge required competent CD4+ T cells, without which no AFCs were generated, even those producing IgM. By contrast, in mice vaccinated with an HA-containing subunit vaccine, fewer AFCs were generated in response to challenge, and these animals were less capable of resisting infection. Our findings demonstrate the comparable localization of AFCs in response to challenge in mice vaccinated with either HA DNA or live virus. Moreover, the former strategy generates both IgG- and IgA-producing plasma cells.

Animals↗

PubMed2003

Clinical significance of interleukin-1 receptor antagonist in patients with cervical carcinoma.

OBJECTIVE: Our purpose was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1ra), which is an endogenous inhibitor cytokine of IL-1, in patients with cervical carcinoma. METHODS: Tissue IL-1ra expression and serum IL-1ra level were examined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry in normal controls and patients with cervical carcinoma. RESULTS: Tissue IL-1ra protein level by ELISA was significantly higher in squamous cell carcinoma (n = 9) than in the normal cervix (n = 7) and adenocarcinoma (n = 3). Western blotting confirmed the main presence of intracellular IL-1ra type 1 in squamous cell carcinoma. Immunohistochemistry demonstrated significant IL-1ra expression only in tumor cells of squamous cell carcinoma. Elevation of serum IL-1ra level was found in patients with squamous cell carcinoma (n = 38) compared to normal women (n = 13), but not in patients with adenocarcinoma (n = 9). Although serum IL-1ra level did not correlate with clinical stage or any other tumor marker, high serum IL-1ra level was associated with pelvic lymph node metastasis and poor prognosis in patients with squamous cell carcinoma. On the other hand, these results were not obtained in patients with cervical adenocarcinoma. CONCLUSION: IL-1ra may play important roles in local and general malignant behaviors in patients with cervical squamous cell carcinoma, and measurement of serum IL-1ra level may be useful in predicting patient survival.

Adenocarcinoma↗

PubMed2005

An hour after immunization peritoneal B-1 cells are activated to migrate to lymphoid organs where within 1 day they produce IgM antibodies that initiate elicitation of contact sensitivity.

Elicitation of contact sensitivity (CS), a classic example of T cell-mediated immunity, requires Ag-specific IgM Abs to trigger an initiation process. This early process leads to local recruitment of CS-effector T cells after secondary Ag challenge. These Abs are produced by the B-1 subset of B cells within 1 day after primary skin immunization. In this study we report the surprising observation that B-1 cells in the peritoneal cavity are activated as early as 1 h after naive mice are painted with a contact-sensitizing Ag on the skin of the trunk and feet to begin the initiation of CS. B-1 cells in the spleen and draining lymph nodes produce the initiating Abs by 1 day after immunization, when we found increased numbers of Ag-specific IgM Ab-producing cells in these tissues by ELISPOT assay. Importantly, we show that contact-activated peritoneal B-1 cells migrate to these lymphoid tissues and then differentiate into Ag-specific IgM Ab-producing cells, resulting in specific CS-initiating IgM Abs in the serum by 1 day. Furthermore, pertussis toxin, which is known to inhibit signaling via G protein-coupled chemokines, inhibited the migration of contact-activated peritoneal B-1 cells to the lymphoid tissues, probably due to BLR-1 (Burkitt lymphoma receptor-1). These findings indicate that within 1 h after contact skin immunization, B-1 cells in the peritoneal cavity are activated to migrate to the lymphoid tissues by chemokine-dependent mechanisms to produce serum Ag-specific IgM Abs within 1 day after immunization, leading to local recruitment of CS-effector T cells.

Animals↗

PubMed2001

Significance of plasma cytokine levels in melanoma patients with histologically negative sentinel lymph nodes.

INTRODUCTION: Although sentinel lymph node (SLN) status is the most powerful predictor of prognosis in patients with clinically localized melanoma, a proportion of melanoma patients with histologically negative SLNs will still recur. It is hypothesized that tumor response may be altered or mediated by specific cytokines. We therefore investigated whether levels of IL-4, IL-6, IL-10, TNF-alpha, or IFN-gamma would predict disease recurrence in melanoma patients with histologically negative SLNs. METHODS: This prospective cohort study involved 218 patients with clinically localized melanoma who underwent a histologically negative SLN biopsy. Preoperative plasma cytokine levels were determined by enzyme-linked immunosorbent assay on these patients, as well as on 90 healthy controls. Kaplan-Meier life tables were constructed, and Cox proportional hazards analyses were performed to assess predictors of disease-free survival (DFS). RESULTS: At a median follow-up of 43 months, 33 of 218 patients (15%) had suffered disease recurrence. Melanoma patients had significant elevations of IL-4, IL-6, and IL-10 compared to healthy controls; levels of IFN-gamma were less elevated in melanoma patients compared to controls. Despite this, melanoma patients with detectable IFN-gamma levels were at significantly higher risk for recurrence compared to patients with undetectable levels (5-year DFS 70% vs. 86%, P = .03). On multivariate analysis including standard melanoma prognostic factors, only tumor thickness (P = .004) and the presence of detectable IFN-gamma levels (P = .05) were significant independent prognostic factors for disease-free survival. CONCLUSIONS: Among melanoma patients with clinically localized disease who have undergone a histologically negative SLN biopsy, presence of a detectable plasma level of IFN-gamma is an independent predictor of disease recurrence. Elevated levels of IFN-gamma may identify a group of early-stage melanoma patients who are more likely to have recurrence of disease and who may benefit from adjuvant therapies, including immunotherapies.

Adolescent↗

PubMed1995

Quantitative polymerase chain reaction analysis reveals marked overexpression of interleukin-1 beta, interleukin-1 and interferon-gamma mRNA in the lymph nodes of lupus-prone mice.

The nature of the stimuli driving autoantibody production in systemic lupus erythematosus (SLE) is unclear, but cytokines are believed to play an important role. Since cytokines primarily appear to act locally at the tissue level, we analysed mRNA expression of several cytokines (IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IFN gamma, TNF alpha, TNF beta and TGF beta 1) in the lymph nodes of lupus-prone mice, in models of early onset disease. We constructed a multispecific competitor fragment that allowed quantification of these cytokine transcripts by competitive PCR assay. The results reveal considerable overexpression of IL-1 beta, IL-10 and IFN gamma transcripts in SLE-prone MRL-lpr/lpr (MRL/l) and BXSB male (BXSBm) mice, but with some strain differences. IFN gamma was most markedly augmented in MRL/l mice (in some cases over 100-fold greater than control mice), IL-1 beta was most severely overexpressed in BXSBm mice while IL-10 was equally increased in both strains. In addition, TGF beta 1 expression was moderately elevated in the lymph nodes of BXSBm (but not MRL/l) mice. We found no abnormality in the expression of the other cytokines. Cytokine transcript levels were only slightly altered at 4 weeks of age, but were elevated from 10 to 22 weeks of age. The latter phase corresponds to a period where lupus-like disease escalates, resulting in frequent mortality. Interestingly, our results do not reveal a clear Th1 or Th2 cytokine expression pattern in these lupus-prone mice. IL-1 beta, IFN gamma and IL-10 are pleiotropic cytokines with pro-inflammatory and B-cell stimulatory effects. These results point to certain cytokines as potential targets for immunotherapy in lupus.

Age Factors↗

PubMed1973

Immune response to a syngeneic rat tumour: development of regional node lymphocyte anergy.

The development of cellular immunity to a syngeneic squamous cell carcinoma in Wistar rats was studied by in vitro microcytotoxicity assay. Reactivity of lymphocytes from lymph nodes, spleen and blood was tested throughout the period of tumour growth. Maximum lymphocyte cytotoxicity against the tumour was observed at 2 weeks in regional lymph nodes, 4 weeks in intermediate nodes, spleen and blood, and 6 weeks in distant nodes; the intensity of these cytotoxic responses subsequently declined. In the regional nodes, lymphocytes became totally unresponsive despite the maintenance of significant cytotoxicity in intermediate nodes, spleen and blood. Local anergy may account for tumour spread to the regional node in an otherwise immunocompetent host. This anergy may be due to high local concentration of tumour antigen or antigen-antibody complexes, but it was not associated with selective changes in T and B cell proportions.

Animals↗

PubMed1999

The back door: venous-mediated metastasis into cervical lymph nodes as an alternative metastatic pathway for oropharyngeal squamous cell carcinoma.

Circulating lymphocytes may home to lymph nodes (LNs) via paracortical postcapillary venules, high-endothelial venules (HEVs) that recognize circulating lymphocytes, enabling them to migrate into nodal cortical/paracortical regions. Our goal was to find any histologic, immunohistochemical, or in vitro evidence to support the hypothesis that squamous cell carcinoma (SCC) may gain access to LNs via an alternative venolymphatic pathway. Slides from 67 neck dissections with SCC were studied. Standard criteria for lymphatic-mediated metastasis were used; criteria for evidence ofvenolymphatic metastasis were tumor nests localized to the paracortical regions, directly contiguous to HEVs but not marginal sinuses. Cases in which LN architecture was obliterated by metastases were excluded. A modified Stamper-Woodruff assay, which assesses HEV binding, incubated cell lines from oral carcinomas and lung adenocarcinomas with fresh frozen LN sections. Double-blinded cell counts were performed by two observers and analyzed by Student's t test. Immunohistochemical examination was undertaken on 19 paraffin-embedded cases with the monoclonal antibody, MoAb CD44v6, to discover whether expression of this adhesion molecule correlated with metastatic pattern. Twenty-nine cases (66%) revealed evidence only for the LN route of metastasis; 4 cases (9%) were classified as venolymphatic metastasis; 11 cases (25%) showed evidence for both pathways. The Stamper-Woodruff assay confirmed that SCC cells preferentially bound to HEV within cervical LN sections more than did adenocarcinoma cells (P = .02). Strong staining to MoAb CD44v6 was seen in 18 (95%) of 19 SCCs with a membranous pattern. Occasionally, CD44v6 highlighted tumor emboli adjacent to HEVs, but no overall correlation could be made between CD44v6 expression and pattern of spread. Tumor metastasis via lymphatic channels is the predominant mode of metastatic spread, but the venolymphatic route is a plausible alternative pathway. The preferential attachment of SCC cells to HEVs supports this theory.

Cell Adhesion↗

PubMed2002

Antigen dose modulates the immunoglobulin isotype responses of pigs against intramuscularly administered F4-fimbriae.

Parenteral immunisation normally induces a systemic antibody response characterised by high IgG and low IgA responses. In the present study, the effect of different doses of F4-fimbriae on the isotype-specific antibody response after intramuscular immunisation was studied in pigs. Pigs were injected twice with a 9 weeks interval with either 1, 0.1 or 0.01 mg of F4-ETEC fimbriae. The dose of 1mg F4 induced significantly lower primary F4-specific IgG and IgM responses than the doses of 0.1 and 0.01 mg F4, but primed for an enhanced F4-specific IgM serum antibody response after the booster immunisation. Furthermore, the dose of 0.1mg induced the highest F4-specific IgA serum response which was significantly higher than after injection with 0.01 and 1mg F4. Moreover, both lower doses (0.1 and 0.01 mg) showed a higher number of F4-specific IgA and IgG antibody secreting cells (ASC) in the local draining lymph nodes of the pigs. This study demonstrated that low doses of purified F4-ETEC fimbriae, especially the 0.1mg dose, are optimal for inducing F4-specific IgA responses after IM immunisation.

Animals↗

PubMed1991

Molecular mapping of functional domains of the leukocyte receptor for endothelium, LAM-1.

The human lymphocyte homing receptor LAM-1, like its murine counterpart MEL-14, functions as a mammalian lectin, and mediates the binding of leukocytes to specialized high endothelial cells in lymphoid organs (HEV). LAM-1 is a member of a new family of cell adhesion molecules, termed selectins or LEC-CAMs, which also includes ELAM-1 and PAD-GEM (GMP-140/CD62). To localize the regions of LAM-1 that are involved in cell adhesion, we developed chimeric selectins, in which various domains of PAD-GEM were substituted into LAM-1, and used these chimeric proteins to define the domain requirements for carbohydrate binding, and to localize the regions recognized by several mAb which inhibit the adhesion of lymphocytes to lymph node HEV. The binding of PPME or fucoidin, soluble complex carbohydrates that specifically define the lectin activity of LAM-1 and MEL-14, required only the lectin domain of LAM-1. The LAM1-1, LAM1-3, and LAM1-6 mAb each strongly inhibit the binding of lymphocytes to HEV in the in vitro frozen section assay, and defined three independent epitopes on LAM-1. Blocking of PPME or fucoidin binding by LAM1-3 indicated that this site is identical, or in close proximity, to the carbohydrate binding site, and analysis of the binding of LAM1-3 to chimeric selectins showed that the epitope detected by LAM1-3 is located within the lectin domain. Although the LAM1-6 epitope is also located in the lectin domain, LAM1-6 did not affect the binding of PPME or fucoidin. The LAM1-1 epitope was located in, or required, the EGF domain, and, importantly, binding of LAM1-1 significantly enhanced the binding of both PPME and fucoidin. These results suggest that adhesion mediated by LAM-1 may involve cooperativity between functionally and spatially distinct sites, and support previous data suggesting a role for the EGF domain of LAM-1 in lymphocyte adhesion to HEV.

Amino Acid Sequence↗

PubMed2002

Dendritic cells and the regulation of a granulomatous immune response in the lung.

To investigate the contribution of dendritic cells (DC) in a pulmonary granulomatous immune response, C57BL/l6 mice, nonimmunized or immunized with purified protein derivative (PPD) of Mycobacterium bovis, were intravenously injected with PPD-coated Sepharose-4B beads. One and three days later lungs were harvested, granuloma size was measured, and immunolabeled cells in granulomas were counted. On Day 1, granulomas in immunized mice were 3-fold larger and contained more major histocompatibility complex class II+, CD11c+ DCs than nonimmunized mice. By Day 3, these differences had diminished. In all granulomas MHC class II+, CD11c+ DCs were in contact with the beads. By in situ hybridization these DCs expressed interleukin (IL)-12 p40 mRNA. MOMA2+ macrophages were present throughout the granulomas, whereas CD4+ and CD8alpha+ T cells were localized at the granuloma periphery. DCs isolated from granulomatous lungs at Day 1, and from thoracic lymph nodes (LNs) at Days 1 and 3, stimulated PPD-specific T cell proliferation without exogenously added antigen, indicating that they had acquired bead-bound antigen. By Day 3, however, granuloma DCs presented little antigen, suggesting that newly immigrated DC lacked access to antigen or that antigen uptake/processing was inhibited. RNase protection assays of whole-lung mRNA showed increased interferon-gamma, IL-1beta, IL-1 receptor antagonist, IL-6, and macrophage inhibitory factor, but no IL-10 mRNA on Days 1 and 3. These observations support the premise that DCs are key in initiating granulomatous cell-mediated immunity. However, factors generated within the granuloma downregulate the antigen presenting function of DC by Day 3 in this experimental model.

Animals↗

PubMed1978

Tissue localization of T-lymphocytes by the histochemical demonstration of acid alpha-naphthyl acetate esterase.

Nonspecific acid alpha-naphthyl acetate esterase (ANAE) activity has previously been evaluated with the sheep erythrocyte (E) rosette assay and found to be a useful T-cell marker in cell suspension studies. T-lymphocytes display a solitary red brown nodule of reaction product (T-pattern) which can be readily distinguished from the diffuse, cytoplasmic staining of monocytes (M-pattern). Freshly obtained human tissue blocks were fixed with buffered formal sucrose and maintained in Holt's syrup; cryostat sections were cut and incubated under conditions appropriate for the histochemical demonstration of lymphocyte acid alpha-naphthyl acetate esterase activity. The results clearly demonstrate that T-pattern ANAE+ lymphocytes populate the paracortical and interfollicular regions of normal lymph nodes and tonsils and the periarteriolar sheaths of normal spleen, T-cell zones, while nearly every germinal center (B-cell area) lymphocyte is ANAE-. Macrophages and dendritic reticulum cells display diffuse cytoplasmic ANAE activity (M-pattern). Nodular malignant lymphomas (B-cell origin) are ANAE-; an E+ diffuse, cutaneous lymphoma was ANAE+. The histochemical demonstration of ANAE activity may represent the first reproducible, routine technique to localize T-lymphocytes in tissue sections.

Carboxylic Ester Hydrolases↗

PubMed2002

Immunological approach in the evaluation of regional lymph nodes of patients with squamous cell carcinoma of the head and neck.

In cancer, regional lymph node (LN) cells are one of the first components of the immune system to have contact with tumor cells or their products. Therefore, the phenotype and functional properties of hematopoietic cells present within the tumor-draining LN are important to understanding their role in the control of malignant cells. Based on the locoregional metastatic behavior of squamous cell carcinoma of the head and neck (SCCH&N) region, we analyzed tumor-draining lymph nodes from SCCH&N patients to obtain insights into regional tumor immunity. Using a three-color fluorescent labeling technique, surface antigen expression was visualized in mononuclear cells of lymph nodes that were obtained from head and neck cancer patients and compared to mononuclear cells of normal lymph nodes. Cell cycle analyses were performed using propidium iodide. Proliferation after phytohemagglutinin stimulation was measured by a sodium tetrazolium-based assay. LN histology was correlated with flow cytometric findings. Regional lymph nodes of head and neck cancer patients undergo morphologic and functional changes. Flow cytometry revealed a decrease in CD8(+) T cells and in some lymph nodes the presence of second or third populations of larger cells with distinct size and granularity that expressed both T (gammadelta/alphabeta) and different natural killer cell markers. Moreover, cell cycle analyses and proliferation assays showed a diminished response to mitogenic stimuli. These changes were found in both metastatic and hyperplastic lymph nodes from head and neck cancer patients; however, no alterations were found in control lymph nodes or peripheral blood mononuclear cells from noncancer patients. The immune alterations detected in lymphocytes present within the draining lymph nodes of head and neck cancer patients may improve our understanding of how tumor cells escape host immunosurveillance. However, this dysfunction in local draining lymph nodes may not be detected systemically.

Adult↗

PubMed2007

Monitoring the genotoxic effects of radiosynovectomy with Re-186 in paediatric age group undergoing therapy for haemophilic synovitis.

PURPOSE: The aim of this study was to investigate the genotoxic effect on the peripheral blood lymphocytes potentially induced by Re-186 in paediatric age group undergoing radiosynovectomy for haemophilic synovitis, by using chromosomal aberration analysis (CA) and the micronuclei (MN) assay for detecting chromosomal aberrations, as well as the sister chromatid exchanges (SCE) technique for assessing DNA damage. METHODS: Cytogenetic analyses were evaluated in 20 boys (mean age: 13.8 +/- 2.7 years) before, and 2 and 90 days after radiosynovectomy from the peripheral lymphocytes of the patients. Joint retention and extra-articular spread of the radionuclides were evaluated by using quantitative gamma camera imaging. RESULTS: Imaging after radiosynovectomy revealed local lymph node visualization in 8 (40%) patients and hepatosplenic visualization in 3 (15%) patients due to extra-articular leakage of radioactive material. The mean frequency of chromosome aberrations (0.2 +/- 0.4/1000 cells) determined prior to the onset of therapy was not significantly increased in comparison with control values obtained 2 days (0.4 +/- 0.5/1000 cells) and 90 days (0.2 +/- 0.4/1000 cells) after therapy (P = 0.754 and P = 1.0). In the analysis of MN and SCE, when we compare the baseline levels, the mean MN and SCE frequencies were slightly higher in the control analyses performed 2 and 90 days after radiosynovectomy but there were no significant differences between baseline and control levels (chi(2) = 2.621, P = 0.270 and F = 0.573, P = 0.569, respectively). CONCLUSION: The major finding of this study with relatively small sample is that, radiosynovectomy with Re-186 does not seem to induce early genotoxic effects on the peripheral blood lymphocytes in paediatric age group.

Adolescent↗

PubMed1992

T-cell-dependent popliteal lymph node reactions to platinum compounds in mice.

The requirements for sensitization to complex salts of platinum were investigated in a mouse model by means of the popliteal lymph node (PLN) assay. A single subcutaneous injection of dissolved hexachloroplatinates without adjuvant induced a vigorous primary immune reaction in the draining PLN. Dose-dependent lymph node activation was determined by an increase in both PLN weight and cellularity. In C57BL/6 mice, peak reactions were obtained around day 6 after administration of 90-180 nmol Na2[PtCl6] or (NH4)2[PtCl6] per animal. Mice primed to [PtCl6]2- mounted an enhanced response upon local restimulation with suboptimal doses of the same but not unrelated compounds, indicating a specific secondary response. T cells were required to elicit PLN reactions to [PtCl6]2-, because athymic nude mice completely failed to respond, in contrast to their +/nu littermates. Differences between various inbred strains of mice revealed that Pt-induced PLN responses are genetically controlled. Moreover, the immunogenicity of Pt salts in mice is not confined to hexachloroplatinates, but other compounds, such as the antineoplastic agent cis-dichlorodiamine platinum, are able to induce comparable PLN reactions.

Animals↗

PubMed1991

Lymphokine-activated killer traffic assay and our preliminary clinical results of regional arterial infusion of lymphokine-activated killer cells for renal cell carcinoma.

In vivo distribution of radiolabeled lymphokine-activated killer (LAK) cells that were administered either through the caudal vein or the abdominal aorta of Lewis rats was studied. The LAK traffic study showed remarkable increase in radioactivity in several organs peripheral to the arterial injection site. We began treating the patients with metastatic renal cancer by means of regional arterial administration of LAK cells. This treatment was supported by the results of the traffic assay. Our regional LAK therapy, which involves a weekly leukapheresis in combination with daily systemic low dose interleukin-2 administration, has been in practice for over 2.5 years. Seven out of 12 metastatic lesions in the 7 patients treated showed regression. Two responding cases have been alive for over 2 years. Responding lesions were bone, muscle, para-aortic lymph node, and/or retroperitoneum. The regional arterial administration of LAK cells is local therapy. However, this mode of therapy could be useful for those patients with extrapulmonary nonresectable metastasis and at least one injectable feeding artery. This study shows our laboratory data concerning the localization of LAK cells transferred via arterial route and our clinical cases treated with regional arterial administration of LAK cells.

Animals↗

PubMed1989

Molecular mechanisms of lymphocyte extravasation. III. The loss of lymphocyte extravasation potential induced by pertussis toxin is not mediated via the activation of protein kinase C.

The present study evaluated whether protein kinase C (PKC) activation was involved in the lymphocytosis promoting properties of pertussis toxin (Ptx). The exposure of mouse lymphocytes to phorbol esters (as a means to selectively activate PKC) caused a depression in their subsequent capacity to localize into lymph nodes and Peyer's patches in vivo. This pattern of inhibition was quite similar to that observed with lymphocytes treated with Ptx. The mechanisms responsible for the observed decreases in localization to lymphoid organs caused by these two agents, however, appeared to be distinct. Exposure of lymphocytes to PMA was followed by a time and dosage-dependent decrease in the surface density of MEL-14 defined homing receptors. Ptx-treated lymphocytes retained normal density of this homing receptor. Consequently, PMA-treated lymphocytes lost their capacity to bind to high-endothelial venules in in vitro lymph node binding assays while Ptx-treated cells retained normal high-endothelial venule binding potential. We conclude from this study that: 1) the activation of PKC in lymphocytes by PMA can alter their recirculation properties via mechanisms that diminish their expression of surface receptors which support extravasation into lymph node and mucosal lymphoid tissues, and 2) even though Ptx has been reported to elevate the rate of inositol phosphate turnover in lymphocytes, the loss of extravasation potential of Ptx-treated lymphocytes is not mediated via the modification of surface homing receptors as observed in cells exposed to the known PKC activator, PMA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMedDate not supplied

Impact of epidermal growth factor (EGF) radioreceptor analysis on long-term survival of gastric cancer patients.

BACKGROUND: The EGF receptor/ligand system seems to be involved in the regulation of gastric mucosa proliferation and progression of gastric carcinomas. PATIENTS AND METHODS: EGF receptor levels were quantitatively determined in 47 gastric carcinomas by 125J [EGF] radioreceptor assays in membrane preparations of tumor samples or corresponding adjacent mucosa. Specific receptor binding was determined by the analysis of displacement curves by non-linear least-square regression analysis using an estimated model of 'goodness of fit'. RESULTS: Increased EGF receptor binding was observed in gastric carcinomas (mean +/- SEM: 11.87 +/- 1.9 fmol/mg protein) in comparison to adjacent normal gastric mucosa ( 5.28 +/- 1.0 fmol/mg protein, p = 0.003). Elevated EGF receptor levels were especially found in more invasive T3/4 carcinomas, tumors with positive lymph nodes, advanced UICC III carcinomas, undifferentiated tumors, carcinomas of the diffuse-type according to Lauren's classification and gastric carcinomas localized distal from the cardia. In histopathologically normal appearing gastric mucosa, EGF-receptor levels were significantly decreased relative to corresponding tumor samples from advanced UICC stages (UICC I vs UICC I/II: p = 0.008) or tumors with low levels of differentiation (G2 vs G3: p = 0.028). Overall survival was significantly reduced in patients with advanced gastric carcinomas according to UICC classification (UICC III vs UICC I/II: 18.8 vs 45.5 months, p = 0.016). A subgroup analysis of gastric carcinomas localized distal from the cardia indicated, that increased EGF-receptor levels were an independent indicator of poor prognosis as determined by univariate (p = 0.020) and multivariate analysis (p = 0.042). CONCLUSION: Gastric carcinomas with increased EGF receptors might be a possible target for anticancer strategies blocking the EGF receptor/ligand pathway.

Epidermal Growth Factor↗