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PubMed1989

[Expression of the epidermal growth factor receptor in esophageal cancer].

The level of epidermal growth factor receptor (EGF-R) has been measured by a competitive binding assay in 45 human esophageal cancer tissues. The EGF-R level in the esophageal cancer tissue was found to be significantly higher than in specimens of gastric or colonic cancer. No correlation was observed, however between the EGF-R level and the pathological findings, such as the depth of the tumoral invasion, the degree of lymph node metastasis, and the histologic staging. Even so, the prognosis of the patients with a high level of EGF-R of more than 50 fmol/mg of protein was significantly worse than those with a low level of EGF-R and less than 50 fmol/mg of protein (p less than 0.01). Further, according to an immunohistochemical assay using anti EGF-R monoclonal antibody, EGF-R was focally stained in the basal cells and in the parabasal cells of normal esophageal mucossa, but was diffuse in almost all tumor cells of ane esophageal cancer. Thus, a good relationship with the quantitative level of EGF-R and its immunoreactivities was demonstrated, indications that EGF-R plays an important role in tumor progression and appears to be a useful prognostic factor in cases of esophageal cancer.

Binding, Competitive↗
PubMed2001

Serum levels of E-selectin, ICAM-1 and VCAM-1 in colorectal cancer patients: correlations with clinicopathological features, patient survival and tumour surgery.

The serum concentrations of the cell adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 63 patients with colorectal cancer and in 51 controls by an enzyme-linked immunosorbent assay (ELISA). Their relationship to clinicopathological variables and patient survival and changes in their levels after surgery were examined. Colorectal cancer patients showed significantly higher serum levels of E-selectin, ICAM-1 and VCAM-1 compared with healthy controls. There was a significant association between the serum levels of these molecules, disease stage and the presence of both lymph node and distant metastases. Both ICAM-1 and VCAM-1 levels correlated with serum E-selectin and carcinoembryonic antigen (CEA) levels. Serum levels of all three molecules decreased significantly after radical resection of the tumour. Elevated pre-operative E-selectin, ICAM-1 and VCAM-1 levels were significant prognostic factors, although not independent of stage, for patient survival. These findings suggest that serum concentrations of E-selectin, ICAM-1 and VCAM-1 may reflect tumour progression and metastasis. Since these markers are linked to CEA levels, it is uncertain whether their measurement will prove cost-effective in colorectal cancer management.

Aged↗
PubMed2002

[The observation of local immune response in the lungs from antigen-sensitized and challenged mice].

OBJECTIVE: To evaluate the local immune response after allergic sensitization and challenge in the lungs of mice. METHODS: C57BL/6 mice were sensitized with keyhole limpet hemocyanin (KLH) by intratracheal instillation and challenged 2 approximately 4 weeks later. Bronchoalveolar lavage fluid (BALF) and plasma were collected and cells from the lung-associated lymph node (LALN), the lungs and the spleen were cultured and collected. Anti-KLH IgA, total IgA and albumin levels were measured by ELISA. RESULTS: Intratracheal instillation of KLH induced local BAL antigen-specific IgA response, and further challenge expanded this response. The ratio of anti-KLH IgA/albumin in BALF was significantly higher than that in serum after both sensitization and challenge by KLH. In vitro, cells from the LALN and the lungs released anti-KLH IgA after sensitization and challenge by KLH, but spleen cells released lower levels of anti-KLH IgA compared to the LALN and the lungs. CONCLUSIONS: Allergic sensitization by intratracheal instillation of KLH into the mouse lungs induced a local pulmonary response of specific IgA, and it was amplified by challenge with KLH. The accumulation of anti-KLH IgA in the respiratory lumen was the result of local production but not the result of simple transudation or leakage from the serum. The LALN and the lung lymphocytes were major sources of anti-specific IgA.

Animals↗
PubMed1980

Tumour-related changes in natural killer cell activity in melanoma patients. Influence of stage of disease, tumour thickness and age of patients.

The influence of tumour growth on the natural killer (NK) activity of melanoma patients was examined by analysis of NK activity in 51Cr release assays before and at intervals after surgical removal of localized melanoma. In patients with Stage I and II melanoma, removal of the tumour was associated with changes in the level of NK activity which were not detected in patients who had surgery for skin graft after previous removal of the primary melanoma. The changes in NK activity after removal of melanoma were however different in patients with Stage I compared to Stage II melanoma. In the former, NK activity which appeared specifically directed toward melanoma cells was maximal 2-4 weeks after removal of the tumour and then decreased to normal levels. The NK activity after surgery was directly related to the thickness of the tumour. In patients with Stage II melanoma, NK activity did not increase but fell to low levels after removal of the tumour. The level of NK activity in these patients was not related to the thickness of their primary melanoma. In patients with Stage I and II melanoma the NK activity against melanoma cells showed a significant increase with age. The reason for the different sequence of changes in NK activity after removal of melanoma in the two patient groups is unknown. It is suggested however that the differences observed in patients with Stage II melanoma may reflect differences in the tumour or host response which contributed to the spread of the tumour to regional lymph nodes in these patients.

Adult↗
PubMed2004

Detection of a sulfotransferase (HEC-GlcNAc6ST) in high endothelial venules of lymph nodes and in high endothelial venule-like vessels within ectopic lymphoid aggregates: relationship to the MECA-79 epitope.

The interaction of L-selectin on lymphocytes with sulfated ligands on high endothelial venules (HEVs) of lymph nodes results in lymphocyte rolling and is essential for lymphocyte homing. The MECA-79 monoclonal antibody reports HEV-expressed ligands for L-selectin by recognizing a critical sulfation-dependent determinant on these ligands. HEC-GlcNAc6ST, a HEV-localized sulfotransferase, is essential for the elaboration of functional ligands within lymph nodes, as well as the generation of the MECA-79 epitope. Here, we use an antibody against murine HEC-GlcNAc6ST to study its expression in relationship to the MECA-79 epitope. In lymph nodes, the enzyme is expressed in the Golgi apparatus of high endothelial cells, in close correspondence with luminal staining by MECA-79. In lymph node HEVs of HEC-GlcNAc6ST-null mice, luminal staining by MECA-79 is almost abolished, whereas abluminal staining persists although reduced in intensity. HEV-like vessels in several examples of inflammation-associated lymphoid neogenesis, including nonobese diabetic mice, also exhibit concomitant expression of the sulfotransferase and luminal MECA-79 reactivity. The correlation extends to ectopic lymphoid aggregates within the pancreas of RIP-BLC mice, in which CXCL13 is expressed in islets. Analysis of the progeny of RIP-BLC by HEC-GlcNAc6ST-null mice establishes that the enzyme is responsible for the MECA-79 defined luminal ligands.

Animals↗
PubMed1994

[Prognostic value of urokinase-type plasminogen activator and 2 inhibitors PAI-1 and PAI-2 in breast cancer].

It is now clearly established that proteolytic enzymes, and in particular plasminogen activator (uPA), play an important role in breaking down the extracellular matrix, which is considered to be a step in metastasis formation. Plasminogen activators are controlled at various levels. Two inhibitors, PAI-1 and PAI-2, have been identified, the latter being more specific for uPA. In attempts to determine their prognostic value, it is essential to investigate the relative importance of these parameters and their interactions. We used an immunoenzymatic method to assay uPA, PAI-1 and PAI-2 antigens in cytosols prepared from 314 primary breast tumors. The patients were followed up for a minimum of six years and all relevant clinical and laboratory findings had been recorded. Univariate analysis confirmed the poor outcome of patients whose tumors contained large amounts of uPA and PAI-1. In addition, low levels of PAI-2 correlated with shorter disease-free survival in the overall population (P = 0.02), post-menopausal women (P = 0.02) and women without lymph node involvement (P = 0.02). Multivariate analysis using the "Main Effects" Cox model identified node involvement, macroscopic tumor size and PAI-2 as significant variables. The "interactive" Cox model, taking into account interactions between uPA and its two inhibitors, identified a first subgroup with a very poor prognosis associating either high levels of PAI-1 with low levels of PAI-2 in the overall population as well as following stratification for axillary node negative disease, or high levels of uPA with low levels of PAI-2 in the group of menopausal women. We conclude that PAI-1 provides the same prognostic informations as uPA, and does not appear to play its role as an inhibitor. In contrast, PAI-2 increased the prognostic value of both uPA, particularly in post-menopausal women, as well as PAI-1 in a subgroup of axillary node negative patients.

Adult↗
PubMed1996

[A case of Lyme borreliosis which was suspected to be caused by Borrelia japonica infection in Shizuoka, Japan].

We report a case of Lyme borreliosis (Lyme disease) found in Shizuoka City, Japan which was suspected to be caused by Borrelia japonica infection. A 8-year-old female was bitten on her head by a tick at a camping ground, near Tamagawa, Shizuoka. The tick was removed by the patient and was discarded before species identification. After one week, lymph node swelling with tenderness developed on her left neck. She consulted a local pediatrician and was suspected to have upper respiratory infection. As oral antibiotic, cefaclor was not effective, the patient was referred to us. The patient's serum showed positive reaction with Lyme Borreliosis ELISA kit (Dakopatts, Denmark) using Borrelia burgdorferi flagellum as antigen. The serum also gave positive results with home-made ELISA to B. japonica strain IKA2, which was isolated from I. ovatus, but not with other borrelial strain isolated in the United States, Europe, and from I. persulcatus and wild rodent in Japan. In western blotting, the serum reacted with flagellin and outer surface protein A (OspA) of B. japonica. We diagnosed her as Lyme disease and got a successful result with oral penicillin, sultamicillin. From a result of our field tick survey, we have not collected I. persulcatus around the area where the patient had a tick bite. These findings indicated that Lyme disease was caused by B. japonica infection with I. ovatus bite.

Antibodies, Bacterial↗
PubMed2006

A mechanism-based combination therapy reduces local tumor growth and metastasis in an orthotopic model of prostate cancer.

Therapy-induced stimulation of angiogenic molecules can promote tumor angiogenesis leading to enhanced tumor growth and cancer metastasis. Several standard and emerging therapies, such as radiation and photodynamic therapy (PDT), can induce angiogenic molecules, thus limiting their effectiveness. PDT is approved for the treatment of several cancers; however, its induction of vascular endothelial growth factor (VEGF) creates conditions favorable to enhanced tumor growth and metastasis, therefore mitigating its cytotoxic and antivascular effects. This is the first report showing that subcurative PDT in an orthotopic model of prostate cancer (LNCaP) increases not only VEGF secretion (2.1-fold) but also the fraction of animals with lymph node metastases. PDT followed by administration of an antiangiogenic agent, TNP-470, abolished this increase and reduced local tumor growth. On the other hand, administration of TNP-470 before PDT was less effective at local tumor control. In addition, animals in all groups, except in the PDT + TNP-470 group, had a weight loss of >3 g at the time of sacrifice; the weight of the animals in the PDT + TNP-470 group did not change. The significant reduction (P < 0.05) in tumor weight and volume observed between the PDT + TNP-470 group and the control group suggests that the combination of PDT and antiangiogenic treatment administered in the appropriate sequence was not only more effective at controlling local tumor growth and metastases but also reduced disease-related toxicities. Such molecular response-based combinations merit further investigations as they enhance both monotherapies and lead to improved treatment outcomes.

Angiogenesis Inhibitors↗
PubMed1999

Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus.

The early events during infection with an immunodeficiency virus were followed by application of pathogenic simian immunodeficiency virus atraumatically to the tonsils of macaques. Analyses by virologic assays and in situ hybridization revealed that the infection started locally in the tonsils, a mucosal-associated lymphoid organ, and quickly spread to other lymphoid tissues. At day 3, there were few infected cells, but then the number increased rapidly, reaching a high plateau between days 4 and 7. The infection was not detected in the dendritic cell-rich squamous epithelium to which the virus was applied; instead, it was primarily in CD4+ tonsillar T cells, close to the specialized antigen-transporting epithelium of the tonsillar crypts. Transport of the virus and immune-activating stimuli across this epithelium would allow mucosal lymphoid tissue to function in the atraumatic transmission of immunodeficiency viruses.

Animals↗
PubMed2005

Prognostic value of telomerase and DNA ploidy in laryngeal carcinoma.

Prognosis of carcinoma of the larynx is currently based on the morphologic analysis of the tumor extent, differentiation grading and type of microscopic invasion. The DNA ploidy status and the cell proliferation activity may give complementary information about the prognosis. Telomerase may be used as a measure of tumor proliferation. The aim of this work was to investigate the probable application of telomerase as a measure of cell immortalization as well as DNA ploidy as a measure of cell proliferation in the prognosis of patients with laryngeal carcinoma. The work was carried out as a prospective observational study that included 35 patients with laryngeal carcinoma who were treated surgically at Ain Shams University Hospitals, Cairo, Egypt. Flowcytometric analysis and biochemical assay of telomerase using human Telomerase Reverse Transcriptase (hTERT) mRNA assay by RT-PCR in resected specimens were done. The proliferative indices in different parts of the tumor were found to be significantly different from each other, with those of tumor edges being the highest. The ploidy status at the edge of the tumor was significantly different between surviving and non-surviving patients, while the tumor core proliferative index was found to be significantly lower in patients without recurrence than those with recurrence. A gradient of telomerase levels was noticed, with levels from tumor cores being the highest followed by tumor edges, resection margins and the lowest levels in lymph nodes. Multivariate analysis showed hTERT levels in tumor edges to significantly affect survival. Both Flowcytometric parameters and telomerase activity may be useful as a prognostic factor for survival in patients with laryngeal carcinoma. Telomerase activity may be used for biologic demarcation for conservational laryngeal surgery, as well as a 'spectral' marker.

Adult↗
PubMed1991

[Evaluation of the "squamous cell carcinoma antigen" as marker of epidermoid cancer of the anal canal].

The authors studied the value of Squamous Cell Carcinoma Antigen (SCC) in squamous carcinoma of the anal canal in 66 patients. Assays were made at the time of diagnosis, before any treatment and during follow-up. A total of 353 assays were made. The positive threshold was selected at 2 ng/ml. At the time of diagnosis, sensitivity of the marker was 44 per cent and its specificity 92 per cent. In our series, pre-treatment SCC levels were not correlated with T by the Papillon classification, but were correlated with lymph node involvement (p less than 0.05). They had no prognostic value at the time of the initial diagnosis. During follow-up, at the time of recurrence, SCC levels were 20.3 +/- 43 ng/ml. This rise was significant (p less than 0.01), the sensitivity of the marker being 77 per cent. In patients who had a recurrence, the outcome was correlated with SCC levels and the latter were of prognostic value (p less than 0.01). In conclusion, SCC levels should form part of the clinical monitoring of patients with a squamous carcinoma of the anal canal.

Adult↗
PubMed2003

Development of surrogate markers for oral immunisation against Candida albicans.

We have developed an oral vaccine using the blastococcoid form of Candida albicans with a murine model of oral candidiasis with infection-resistant (BALB/c) and infection-prone (DBA/2) mice. Previous studies had demonstrated that enhanced clearance was linked to increased production of both Th1 and Th2 cytokines (IFN-gamma and IL-4, respectively) in regional lymph nodes, and increased secretion of IFN-gamma and NO in saliva. Subsequent study using oral Lactobacillus acidophilus (LAVRI-A1) induced a local cytokine pattern and enhanced clearance of intra-oral C. albicans similar to that noted in animals given killed candida vaccine. Thus, the experiment was repeated with a 2 month gap between completion of a vaccine course and challenge with live C. albicans. Compared to control mice, those given the oral vaccine had a 4 log reduction in colonisation on day 2, associated with twice the levels of secretion of IFN-gamma and IL-4 from the regional node cells, five times the level of nitric oxide in saliva, and suppression of NO production with MMLA induced a 2 log increase in oral colonisation. Thus while both IFN-gamma and IL-4 appear to contribute to clearance of oral C. albicans, IL-4 appears to act through a paracrine enhancement of NO production. Studies in man are in progress to define similar surrogate markers of immune protection, prior to oral vaccine trial.

Administration, Oral↗
PubMedDate not supplied

Evaluation of serum carcinoembryonic antigen monitoring in the follow-up of colorectal cancer patients with metastatic lymph nodes and a normal preoperative serum level.

The value of serial serum carcinoembryonic antigen (CEA) assay in the follow-up of colorectal cancer patients with metastatic lymph nodes and normal (< or = 5 ng/ml) preoperative CEA levels, was examined in this study. Thirty-eight patients were studied and compared with 22 patients with elevated CEA levels. The overall sensitivity of CEA for the diagnosis of recurrence was 36%. Postoperative CEA was strongly influenced by the site of recurrence. CEA monitoring showed the best results in patients who developed hepatic metastases (sensitivity 60%, specificity 94%, positive predictive value 60%, and negative predictive value 94%), and was ineffective for the detection of locoregional or pulmonary metastases. The results indicate that elevation of CEA in the postoperative course of these patients is an indicator of the presence of hepatic metastases. Postoperative CEA monitoring should not be omitted in Dukes C patients with normal preoperative levels, and is more reliable for the detection of liver metastases.

Adult↗
PubMedDate not supplied

Impaired induction of delayed hypersensitivity following anterior chamber inoculation of alloantigens.

BALB/c mice that receive allogeneic P815 tumor cells (DBA/2 origin) into the anterior chamber of the eye (intracamerally, i.c.) fail to develop DBA/2-specific delayed hypersensitivity (DH). We have previously shown that this failure results, in part, from the generation of efferent T suppressor cells. To determine whether DH effector cells are even activated in these mice, a local adoptive transfer assay for DH was developed: Mixtures of responder lymphocytes and irradiated stimulator cells were injected into the pinnae of normal mice, syngeneic with the responders. In this assay, spleen cells from i.c. injected donors failed to evoke a local DH. Moreover, when spleen cells from i.c. injected donors were mixed with specifically immune BALB/c anti-DBA/2 lymphoid cells and similarly assayed, DH was effectively suppressed. Spleen cells from i.c. injected mice, depleted of Lyt-2+ suppressor cells, remained unresponsive in this assay, even if before injection they had been exposed to 5 days of in vitro culture with DBA/2 alloantigens. We conclude that anterior chamber inoculation of P815 cells in BALB/c mice fails to activate DH effector cells. Therefore, the inability of i.c. injected mice to mount DH responses results not only from efferent suppression but also from selective impairment of DH induction. The latter effect may be due to the activation of an afferent suppressor mechanism that acts selectively on T cell help for DH but that has no effect on help for B cells or cytotoxic T cell precursors.

Animals↗
PubMed1996

Advances in the assessment of clinically localized prostate cancer.

OBJECTIVE: We review the advances in pathology, biology, and radiology which could improve the detection of extracapsular prostate cancer preoperatively. METHOD: The experiences of others are compared to ours to give a topical overview of advances in the assessment of clinically localized prostate cancer. RESULTS: Despite new technologies, such as colour Doppler and endorectal magnetic resonance imaging, radiology does not enhance the ability to detect small invasion through the prostatic capsule. Biopsy features are one of the new fields of investigation. The number of positive sextant biopsies and the analysis of periprostatic spaces on biopsies appear to be major prognosis factors. In our experience, capsular perforation on biopsy is very powerful with respect to the proportion of positive biopsies ( > 66.7%) and serum PSA ( > 25 ng/ml, polyclonal assay) to predict biological progression after radical prostatectomy. The utility of the proportion of invaded tissue on biopsy is still debated. CONCLUSIONS: Despite technical improvements, the staging of clinically confined prostate cancer is still a major issue. The best hope comes from the study of biopsy features in addition to PSA.

Biopsy↗
PubMed2002

Preoperative plasma levels of interleukin-6 and its soluble receptor predict disease recurrence and survival of patients with bladder cancer.

PURPOSE: Elevated levels of interleukin-6 (IL-6) are associated with metastasis and poor prognosis in various malignancies. Since the IL-6 soluble receptor (IL-6sR) potentiates the systemic effects of IL-6, each may independently impact the disease process. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels would predict cancer stage and prognosis in patients with transitional cell carcinoma of the bladder. MATERIALS AND METHODS: The study group consisted of 51 patients who underwent radical cystectomy for transitional cell carcinoma and 44 men without cancer. Preoperative plasma levels of IL-6 and IL6sR were measured by enzyme-linked immunosorbent assay and correlated with pathological features and clinical outcome. RESULTS: IL-6 levels were higher in patients with bladder cancer than in healthy controls (p <0.001). In bladder cancer cases elevated levels of IL-6 and IL-6sR were associated with adverse pathological features, including muscle invasion, lymphovascular invasion and lymph node metastases (p <0.05). High levels of IL-6sR were also associated with pathological tumor grade (p = 0.036). In separate multivariate models that included clinical stage and grade IL-6 and IL-6sR levels were independent predictors of lymphovascular invasion, metastases to lymph nodes, disease recurrence and disease specific survival (p <0.05). In a preoperative Cox proportional hazards model IL-6 (p = 0.050) and IL-6sR (p = 0.035) predicted disease specific survival. CONCLUSIONS: We found that plasma IL-6 levels were higher in patients with bladder cancer than in healthy controls. Levels of IL-6 and IL-6sR were associated with cancer stage and metastases, and were strong independent predictors of disease recurrence and disease specific survival.

Adult↗
PubMed1999

Immunohistochemical localization of caspase-3 correlates with clinical outcome in B-cell diffuse large-cell lymphoma.

Although B-cell diffuse large-cell lymphoma (DLCL) can respond to chemotherapy and radiotherapy, a large number of patients are still resistant to treatment. Caspase-3 is an enzyme crucial to the apoptotic process and may be important in the clinical outcome of these patients. The pattern of caspase-3 expression was studied in 54 cases of DLCL using immunohistochemistry and quantitative reverse-transcription PCR. Tumor cells displayed both a diffuse cytosolic and a punctate cytosolic staining for caspase-3. Kaplan-Meier survival curves indicated that tumor cells with a diffuse cytosolic expression of caspase-3 correlated with a poor prognosis (P > 0.0004). In addition, a punctate cellular localization was associated with complete response to treatment (P = 0.011). Cases with a small percentage of lymphoma cells expressing caspase-3 also tended to show poor survival (P > 0.09). Levels of caspase-3 mRNA were not significant (P > 0.17), although a weak trend was observed similar to the immunohistochemical analysis. The pattern of expression of caspase-3 was also assessed with respect to terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) positivity in both reactive lymph nodes and B-cell DLCL cases. Our results suggest that TUNEL-positive cells are not caspase-3-positive and that there is no correlation between DLCL cases with a high degree of DNA fragmentation and caspase-3 immunostaining. Furthermore, a survival curve indicated that a high TUNEL positivity was associated with a poor survival probability (P < 0.02) and a poor response to treatment (P = 0.04). These results confirm the dynamic nature of caspase-3 expression in DLCL and suggests that the pattern of expression of the enzyme has prognostic significance.

Adolescent↗
PubMed1997

Significance of proliferating cell nuclear antigen expression in liver metastasis of colorectal cancer.

PURPOSE: The study contained herein was aimed at finding some possible pathologic factors that have significance for the prediction of liver metastasis in colorectal cancer. METHOD: Resected specimens of colorectal cancer from 23 patients with liver metastasis and 30 patients without liver metastasis were subjected to pathologic study, including microscopic characteristics and proliferating cell nuclear antigen immunohistochemistry assay. RESULTS: Strongly positive expression of proliferating cell nuclear antigen was present in 65.21 percent (15/23) of the liver metastasis group, whereas it was found in only 20 percent (6/30) of the group without liver metastasis (P < 0.005). Deeper invasion to the muscularis propria or serosa and less infiltration of lymphocytes surrounding the tumor were more frequently found in the liver metastasis group than in the other group (P < 0.025). CONCLUSION: Extent of proliferating cell nuclear antigen expression, depth of invasion, and reaction of lymphocyte infiltration of the primary tumor could have predictive significance of colorectal cancer in liver metastasis.

Adult↗