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PubMedDate not supplied

Antifertility effects of neem (Azadirachta indica) oil in male rats by single intra-vas administration: an alternate approach to vasectomy.

An alternate approach to vasectomy for long-term male contraception following a single intra-vas application of a traditional plant (Azadirachta indica) product having immunomodulatory properties is described. Male Wistar rats of proven fertility were given a single dose (50 microliters) of neem oil in the lumen of the vas deferens on each side; control animals received the same volume of peanut oil. Animals were put on continuous mating 4 weeks after the treatment, with females of proven fertility. While the control animals impregnated the female partners, all males treated with neem oil remained infertile throughout the 8 months of observation period. Epididymal and vas histology were normal without any inflammatory changes or obstruction. The intra-vas administration of neem oil resulted in a block of spermatogenesis without affecting testosterone production; the seminiferous tubules, although reduced in diameter, appeared normal and contained mostly early spermatogenic cells. No anti-sperm antibody could be detected in the serum. Unilateral administration of neem oil in the vas resulted in a significant reduction of testicular size and spermatogenic block only on the side of application; the draining lymph node cells of the treated side also showed enhanced proliferative response to in vitro mitogen challenge. These results indicate that the testicular effects following intra-vas application of neem oil may possibly be mediated by a local immune mechanism.

Animals↗
PubMed1998

Time course of the porcine cellular and humoral immune responses in vivo against pseudorabies virus after inoculation and challenge: significance of in vitro antigenic restimulation.

We investigated the time course of porcine cellular and humoral immune responses against pseudorabies virus (PRV) after pigs were inoculated with PRV gE(-) mutant strain M141 and challenged with wild-type virus NIA-3. Peripheral blood mononuclear cells (PBMC) were isolated from blood samples; half were used directly and half were restimulated with PRV in vitro before use in a cytolytic assay. We determined time course and extent of PRV-specific lymphoproliferative and cytolytic response. In addition, serum samples were examined for neutralizing antibodies. After inoculation, the frequency of various lymphocyte subsets in peripheral blood was determined by FACScan. One week after inoculation, T-lymphocytes proliferated abundantly and a B-lymphocyte response was observed. When PBMC were used directly without restimulation, only 15% of the PRV-infected target cells were lysed, and about 15-20% of uninfected target cells were lysed. In contrast, when PBMC were restimulated with PRV, up to 50% of the PRV-infected target cells were lysed while only 30% of the uninfected target cells were lysed. The frequency of various T-lymphocyte subsets in the circulation did not change significantly after inoculation, which indicates that the number of PRV-specific lymphocytes in circulation was very small. After challenge, the T-lymphocyte response was enhanced, but the B-lymphocyte response was not. When PBMC were used directly, only 20% of the PRV-infected and uninfected target cells were lysed after challenge. In contrast, when PBMC were restimulated with PRV, they again lysed more PRV-infected target cells than uninfected target cells. Cytolytic cells were detected for a longer period after challenge than after inoculation. Since it was only possible to clearly detect cytolysis after lymphocytes were restimulated with PRV, it may be that they do not preferentially localize in blood or that they are too few in blood to be detected without further antigenic restimulation in vitro. These lymphocytes may instead localize in other tissues, such as mucosal tissues, tonsils and draining lymph nodes. Whether such a reservoir of PRV-specific cytolytic cells is important in clearing the virus is still unknown. In this study we demonstrated PRV-specific lymphocytes in circulation after they were restimulated in vitro with PRV.

Animals↗
PubMed1999

Tumor necrosis factor-alpha and virus expression in the central nervous system of cats infected with feline immunodeficiency virus.

Cytokine disregulation has been implicated in the pathogenesis of lentivirus-induced diseases. In the present study, 18 specific pathogen free (SPF) cats were inoculated with feline immunodeficiency virus (FIV) Petaluma strain and sacrificed at different times post-infection. Five additional SPF cats were used as controls. The cell localization of the cytokine tumor necrosis factor alpha (TNF-alpha) in the central nervous system (CNS) was determined by immunohistochemical and morphometric analyses with a polyclonal rabbit anti-human TNF-alpha antibody. TNF-alpha and FIV RNA were measured using competitive reverse transcriptase polymerase chain reaction (PCR) assays and the number of proviral genomes was estimated by competitive PCR. Portions of frontal cortex were collected from each animal and both formalin-fixed and snap-frozen and stored at -80 degrees C until used. The results showed that TNF-alpha is present mainly in astrocytes and microglial cells. Morphometric analysis showed that areas of TNF-alpha production increased in the early phases of infection. Molecular analyses demonstrated that the kinetics of proviral loads in the CNS were comparable to what observed in lymph nodes and peripheral blood mononuclear cells, with the peaks in the early and late stages of infection. A positive correlation was found between viral parameters and TNF-alpha transcription, the strongest relationship was found between the transcription of the cytokine and viral RNA load. These results confirm that invasion of CNS by FIV occurs soon after virus exposure and that during this phase there is an increase of local viral loads with concomitant up-regulation of TNF-alpha expression. During the asymptomatic phase viral replication remains low in spite of the progression of CNS alterations. The dissociation between the viral load and the lesions observed suggests the importance of an indirect mechanism for the progression of these lesions, even if TNF-alpha seems to play a role particularly in the early phase of infection.

Animals↗
PubMed2000

Stromal cell-derived factor-1 as a chemoattractant for follicular center lymphoma B cells.

BACKGROUND: Follicular center lymphoma displays widespread lymph node involvement at diagnosis. The chemoattractants that control the locomotion of follicular center lymphoma B cells have not been established. Stromal cell-derived factor-1 (SDF-1) is a CXC-class chemokine that enhances the migration of normal human B cells and is expressed in peripheral lymphoid tissues. Here we have investigated 1) whether SDF-1 stimulates the in vitro locomotion of follicular center lymphoma B cells and of their presumed normal counterparts (i. e., germinal center B cells) and 2) whether the same cells express SDF-1 transcripts. METHODS: B cells were purified by immunomagnetic bead manipulation. Messenger RNA was detected by reverse transcription-polymerase chain reaction. Migration was assessed by the filter and collagen invasion assays. All P values were two sided. RESULTS: Follicular center lymphoma B lymphocytes showed a statistically significant migratory response to 300 ng/mL SDF-1, both in the filter and in the collagen assays (P =.002 for each). Such response was mediated by the SDF-1 receptor, CXCR4. CD40 monoclonal antibody (MAb) and tonsillar germinal center B cells treated with CD40 MAb and recombinant interleukin 4, but not freshly isolated, migrated statistically significantly faster in the presence than in the absence of SDF-1 (P =.002 in both filter and collagen assays). Freshly isolated follicular center lymphoma and germinal center B cells expressed SDF-1 transcripts. CONCLUSIONS: This study shows that SDF-1 substantially enhances the migration of follicular center lymphoma B cells but not the migration of freshly purified germinal center B cells. This difference may be related to the extended survival of follicular center lymphoma versus germinal center B cells. SDF-1 produced in follicular center lymphoma lymph nodes may play a role in the local dissemination of tumor cells.

Antibodies, Monoclonal↗
PubMed1994

A possible prognostic role of immunoglobulin-G antibody against recombinant Epstein-Barr virus BZLF-1 transactivator protein ZEBRA in patients with nasopharyngeal carcinoma.

BACKGROUND: Epstein-Barr virus BZLF-1 replication activator (ZEBRA) is involved in the switch from viral latency to a productive cycle. Previous immunofluorescent study has shown that patients with nasopharyngeal carcinoma (NPC) have elevated immunoglobulin-G (IgG) antibody titres against recombinant ZEBRA protein (ZEBRA/IgG). METHODS: The prognostic role of ZEBRA/IgG was further investigated by enzyme-linked immunosorbent assay (ELISA) in 110 NPC patients under long period of clinical follow-up. RESULTS: Ninety-seven percent (85 of 88) of the patients with NPC had significantly higher ZEBRA/IgG titres (geometrical mean titre, i.e., GMT = 8397) than normal Chinese individuals (GMT = 233 and P < 0.0001). Based on Kaplan-Meier analysis, the actuarial survival in patients with high ZEBRA/IgG titres (25%) after radiotherapy was significantly lower than that of those with low (76%; P = 0.0008) or intermediate titres (62%; P = 0.0036), although the titres taken before treatment did not bear such a relationship. Subdividing the patients into either individual UICC or Ho's stages, those with late-stage disease (UICC Stage 4 and Ho's Stages 3 and 4) and with high ZEBRA/IgG titres also had poorer prognosis than those with disease of the same stages but who had low titres. Poor prognosis in those with high titres could be associated with a high risk of distant metastasis because consistent titre increase was found in the majority of patients who later developed distant metastasis either in the lung or liver. Only a minimal increase was found in patients with recurrence in the cervical lymph nodes. No consistent increase was observed, however, in patients whose disease was in remission or the majority of those with bone metastasis or local recurrence in the nasopharynx. CONCLUSION: The postradiotherapy ZEBRA/IgG titre could be a potentially useful marker for differentiating NPC patients with poor prognosis from those at high risk for the development of distant metastasis to the lung or liver.

Biomarkers, Tumor↗
PubMed1979

Clinical value of carcinoembryonic antigen: diagnosis, prognosis, and follow-up of patients with cancer.

Plasma carcinoembryonic antigen (CEA) in nanograms per milliliter was assayed in 149 patients with benign and 567 patients with malignant disease. Elevated CEA level (greater than 5.0) was a good indicator of malignant disease but a poor screening test for cancer because of the high false-negative rate. Degree of elevation of plasma CEA level correlated with incidence of metastatic disease in patients with colorectal, gastric, and breast carcinomas, but no correlation was seen between CEA levels and status of lymph nodes in patients with localized disease. Patients with localized colorectal cancer, but elevated CEA levels before resection, had a 2.1-fold increase in the incidence of recurrence; however, this added to the prognostic value of Dukes' staging only when the CEA level remained elevated postoperatively. In 87% of patients with colorectal cancer, the CEA level was elevated at the time of recurrence, but a therapeutic value of reexploration for unexplained CEA level elevation was not confirmed.

Carcinoembryonic Antigen↗
PubMed2003

Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with Stage IV melanoma.

BACKGROUND: Based on the likelihood of transfecting large numbers of local antigen-presenting cells, a Phase I study in patients with Stage IV melanoma was conducted to determine the practicality, toxicity of, and immune responses to repeated infusions into a groin lymph node of escalating doses of a DNA plasmid encoding tyrosinase epitopes. METHODS: Cohorts of 8 patients each received 200 microg, 400 microg, or 800 microg of DNA intranodally by pump over 96 hours every 14 days for 4 cycles. Blood was collected for immunologic assays and to measure plasmid in serum prior to treatment, 4 weeks later, and 8 weeks later. Scans and X-rays were performed at baseline and after 8 weeks. RESULTS: Treatment was tolerated well, with only five patients demonstrating Grade 1-2 toxicity. Vaccine delivery by 96-hour infusions of plasmid into a groin lymph node resulted in only 1 episode of catheter leakage in 107 cannulations. Detection of plasmid in serum was rare and transient in two patients. Immune responses by peptide-tetramer assay to tyrosinase 207-216 were detected in 11 of 26 patients. No clinical responses were seen. Survival of the heavily pretreated patients on this trial was unexpectedly long, with 16 of 26 patients alive at a median follow-up of 12 months. CONCLUSIONS: Infusion of a DNA plasmid vaccine into a groin lymph node was practical and well tolerated. Immune responses to a novel tyrosinase epitope were noted. Overall survival in this trial of heavily pretreated patients was unexpectedly long, with 16 of 26 patients alive after a follow-up of 12 months, favoring immune responders.

Adult↗
PubMed2006

Inflammatory cytokines predominate in cases of tumor regression after hematopoietic stem cell transplantation for solid cancer.

Allogeneic hematopoietic stem cell transplantation (SCT) has recently been presented as promising immunotherapy against renal cell, colon, ovarian, breast, and primary liver cancer. Because clinical results demonstrate a variable effect on metastases, we studied whether there is an association between the clinical response and free cytokines in serum. Two patients with metastatic colorectal and 4 with renal cell cancer underwent allogeneic SCT. Conditioning included fludarabine (30 mg/m2) for 3 or 5 days, using sibling or matched unrelated donors, respectively, followed by 2 Gy total body irradiation (n=5) or cyclophosphamide (60 mg/kg) for 2 days (n=1). Antithymoglobuline (4 mg/kg) was given to patients with matched unrelated donors (n=3). Immunosuppression was cyclosporin A, combined with mycophenolate mofetil (n=5) or methotrexate (n=1). The tumor load was examined by computer tomography of the thorax and abdomen before and 3, 6, 9, and 12 months after SCT. Free cytokines in serum were analyzed using enzyme-linked immunosorbent assay. In each patient, the ratio between inflammatory (I) and anti-I cytokines was calculated. No statistical significance was found between the cytokine ratio in correlation to the tumor load according to international response evaluation criteria in solid tumors criteria. In contrast, tumor regression was found to correlate with dominating I cytokine levels in 5/7 occasions, compared with 1/12 of cases with anti-I cytokines using our local method focusing on metastases in lungs, lymph nodes, and liver (P=.01). Thus, an increased level of I cytokines possibly mirrors tumor killing induced by type 1 T-cell response. Furthermore, anti-I cytokines might inhibit cytotoxic cells from exerting the antitumor effect of allogeneic SCT.

Aged↗
PubMed2000

In vitro studies on the trafficking of dendritic cells through endothelial cells and extra-cellular matrix.

Dendritic cells (DC) are antigen presenting cells (APC) with the unique ability to initiate an immune response. Immature DC are localized in peripheral tissues where they exert a sentinel function for incoming antigens (Ag). After Ag capture and exposure to inflammatory stimuli DC undergo maturation and migrate to regional lymph nodes where the presentation of antigenic peptides to T lymphocytes takes place. Thus their correct functioning as APC involves localization in tissues and trafficking via the lymph or blood to lymphoid organs. In the present study we have investigated the ability of DC to interact in vitro with human vascular endothelial cells (EC) and extracellular matrix (ECM). DC are differentiated from monocytes by in vitro exposure to GM-CSF and IL-13 for 7 days. In adhesion assays a considerable proportion of DC binds to resting EC monolayers and this adhesion is inhibited by anti-CD11a and CD11b, but not anti-CD11c mAbs. Binding to a natural ECM, derived from cultured EC involves VLA-4 and VLA-5 integrins. In a transmigration assay, 10% of input cells are able to cross the EC monolayer in the absence of exogenous stimuli. The amount of DC transmigrated through a monolayer of EC was increased of 2-3 fold by C-C chemokines RANTES, MIP1alpha, and MIP-1beta. Most importantly, in view of the trafficking pattern of these cells, a significant proportion of DC can migrate in a reverse transmigration assay, i.e. across the endothelial basement membrane and subsequently, across endothelial cells. Upon exposure to immune or inflammatory signals peripheral DC undergo maturation and migration to lymphoid organs. Functional maturation is associated with loss of responsiveness to chemokines present at sites of inflammation (e.g. MIP1alpha, MIP1beta and RANTES) and acquisition of a receptor repertoire which renders these cells responsive to signals which guide their localization in lymphoid organs (e.g. MIP3beta). A better understanding of the molecular basis of DC trafficking may provide molecular and conceptual tools to direct and modulate DC localization as a strategy to upregulate and orient specific immunity.

Cell Adhesion↗
PubMed1999

Vascular endothelial growth factor in acute Kawasaki disease.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is an important regulator of angiogenesis and blood vessel permeability. Kawasaki disease (KD) is characterized by systemic vasculitis with increased vascular permeability, implying a possible role of VEGF in KD. To elucidate the involvement of VEGF in the pathogenesis of KD, we investigated 30 patients with acute KD, comparing the time course of plasma VEGF levels (n = 123) with clinical symptoms and laboratory findings. Compared with control values, the peak levels of plasma VEGF were significantly elevated (38+/-26 vs 244+/-248 pg/ml, p <0.001). The VEGF levels at the appearance of skin rash and/or edema of hands and feet were also elevated to 176+/-163 pg/ml (p <0.001). In 7 patients (23%), the plasma VEGF levels remained increased after the resolution of the skin rash and peripheral edema. The VEGF levels were independent of gamma globulin therapy and levels of serum albumin and C-reactive protein. We also measured the plasma levels of transforming growth factor-beta1 (TGF-beta1) and tumor necrosis factor alpha, both of which can upregulate VEGF in vitro. The plasma levels of VEGF were highly correlated with those of TGF-beta1 (n = 63, r = 0.73, p <0.001) but not with those of tumor necrosis factor alpha. These findings suggest that the production of VEGF is increased and may be upregulated by TGF-beta1 in acute KD. VEGF may be involved in the hyperpermeability of local blood vessels in acute KD.

Biomarkers↗
PubMed2003

Time trends in biochemical recurrence after radical prostatectomy: results of the SEARCH database.

OBJECTIVES: To determine whether in the prostate-specific antigen (PSA) era stage and/or grade migration of patients treated with radical prostatectomy (RP) has occurred. We also examined whether the biochemical recurrence rates after RP have changed with time. METHODS: A total of 1654 patients from the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed for time trends in age, preoperative PSA level, clinical stage, biopsy Gleason score, prostatectomy Gleason grade, pathologic stage, margin status, and recurrence rates after RP. Results were stratified into three 4-year blocks of time between 1988 and 2002 for analysis. RESULTS: The preoperative PSA level, patient age, tumor stage, rate of capsular penetration, and lymph node involvement decreased with time. Both biopsy and pathologic Gleason grade steadily increased with time. The positive margin rate and incidence of seminal vesicle involvement remained stable. On multivariate analysis, only serum PSA level (P <0.001) and biopsy Gleason score (P <0.001) were significant independent predictors of the time to recurrence after RP. The year of surgery was not a significant independent predictor of biochemical recurrence after RP in multivariate analysis. CONCLUSIONS: Despite lower stage and lower PSA levels with time, we found no improvement in PSA recurrence rates over time. This may reflect lead-time bias in detecting PSA recurrence by the use of more sensitive PSA assays in recent years.

Age Factors↗
PubMed1977

Immunocytochemical localization of lysozymes in respiratory and other tissues.

Immunostaining paraffin sections of appropriately fixed tissues with an antiserum to human urinary lysozyme as the primary step in an immunoglobulin-peroxidase bridge method has localized lysozyme in previously recognized sites such as Paneth cells, renal tubules, and lymph node macrophages in several species. In addition, lysozyme was demonstrated in the ciliary layer of the trachea, and type II pneumocytes, as well as cells of presumed mucoid nature in laryngotracheal glands. Large stellate cells in follicle centers in the lymph nodes and spleen and in the medulla of the thymus evidenced strong lysozyme reactivity. Granular pneumocytes disclosed immunoreactivity for lysozyme also at the ultrastructural level. Lysoplate assay demonstrated lysozyme in abundance in both the cellular pellet and acellular supernatant of rat alveolar wash fluid and in rat lung after repeated washing of alveoli. Hamster lung differed from the others in failing to immunostain for lysozyme and affording no evidence for content of lysozyme as determined by lysoplate assay. Sites stained with antiserum to human urinary lysozyme failed to stain with antiserum to egg white lysozyme. However, the pyloric glands, Golgi elements in intestinal epithelium, the surface of the colon, and the proximal straight renal tubule of the mouse stained exclusively with the antiserum to hen egg white lysozyme. Many sites staining with antiserum to urinary lysozyme in respiratory, renal, and lymphoid tissue lacked reactivity in control sections exposed to this antiserum after it was absorbed with purified urinary lysozyme. However, mucous acini in submandibular glands, although failing to stain with other control procedures, retained towared the absorbed antiserum, possibly through reacting with an antibody other than that for human urinary lysozyme. A number of cell types containing proteinaceous cytoplasmic granules stained in control sections exposed to normal serum in place of antilysozyme serum in the immunoglobulin-peroxidase bridge procedure and, thus, possessed selective, but nonimmunospecific affinity for immunoglobulin. Cell types that stained with antiserum to hen egg white lysozyme lost affinity for the antiserum after its absorption with egg white lysozyme but retained the affinity after absorption with urinary lysozyme.

Animals↗
PubMed2003

Effect of tumor stage and nephrectomy on CD62P expression and sP-selectin concentration in renal cancer.

The CD62P receptor and its soluble form sP-selectin is a marker of platelet (PLT) activation, and constitutes a ligand for CD24 antigen of neoplastic cells and tumor stroma components. The aim of the study was to evaluate the relationship dynamics of the percentage of CD62P+ platelets, the level of the receptor expression and the concentration of soluble form of sP-selectin in renal cancer. Examinations were performed before and after nephrectomy in patients with renal cancer (group A - 25, T2N0M0; group B - 27, T2N1-2M0) and in control group (C - 24 subjects). The two groups A and B showed an increased subpopulation of CD62P+ platelets (p<0.01) and elevated sP-selectin concentration (p<0.001) before and after nephrectomy. Although following nephrectomy sP-selectin concentration decreased markedly, it was still higher 3 months after the procedure compared to control group (p<0.05). Following nephrectomy, however, no statistically significant differences were found in the % of CD62P+ platelets and the receptor expression. Greater dynamics of changes before and after nephrectomy in the percentage of CD62P+ platelets (B1:B2 p<0.05) and the receptor expression (B1:B3 p<0.001) was observed in patients with local lymph node involvement (group B) while sP-selectin concentration was similar in both groups. Nephrectomy did not normalize intravascular activation of PLT and TNM had no significant effect on the expression of CD62P and concentration of sP-selectin.

Adult↗
PubMed1992

Murine intestinal humoral responses in chronic Schistosoma mansoni infections.

Specific and non-specific production of immunoglobulins (Ig) by the intestinal mucosa was examined in mice infected with the human blood fluke Schistosoma mansoni. Ileal and colonic mucosal tissue samples were cultured for 2 days, the medium replaced and the culture continued for a further 2 days. Ig concentrations and specific antibodies to soluble schistosome egg antigens in culture supernatants were estimated by isotype-specific ELISA. Cultured mucosae from control mice produced little IgG, but significant amounts of IgA and IgM on prolonged culture. IgG concentrations were increased in infected animals, mainly in the initial culture period, indicative of systemic, rather than local origins. By contrast, significantly increased local production of IgA and IgM occurred after the start of egg deposition in the intestinal mucosae. Although specific anti-egg antibodies of the IgG and IgM class were detected, none of the local IgA response was specific for schistosome eggs. We conclude that specific intestinal immune responses to schistosome eggs reflect systemic responses, whereas locally increased IgA production is largely non-specific. This pattern of response is likely to be related to the prior systemic exposure to schistosome eggs, which results in polyclonal local B-cell activation, but fails to trigger an antigen-specific IgA mucosal response.

Animals↗
PubMed1986

Limiting dilution analyses for the quantification of cellular immune responses in bovine ostertagiasis.

A sensitive limiting dilution analysis (LDA) was used to quantitate the local and systemic cellular immune response of cattle after immunization with keyhole limpet hemocyanin (KLH) and infection with Ostertagia ostertagi. The assay measures the proliferative response of bovine T-cells after in vitro stimulation with antigen. Interleukin 2 activity was supplied by supernates from mitogen-stimulated bovine peripheral blood lymphocytes (PBL) and accessory cell function was in the form of irradiated autologous PBL. The assay measures the response of a single cell and was most easily demonstrated in the lymph nodes draining the site of antigen inoculation. Comparison of cell frequencies and maximal responses generated in conventional proliferative assays showed several differences between the two assays. First, after antigen injection, the highest cell frequencies were seen in the draining lymph nodes within 3 days, and decreased by 10 days post-immunization. In contrast, in mass cultures maximal stimulation was not seen until 7-10 days after injection, but remained high up to 4 weeks after immunization. Second, at 17 days post-infection, a time of eruption of the parasite from the gastric glands, high frequencies of inducible cells were demonstrated by LDA in all lymphoid populations tested. In contrast, low levels of proliferation were seen in mass cultures. The reasons for these differences may include different sensitivities to suppression or more stringent requirements for specificity between the two assays. Finally, it was found that immunologically naive calves have relatively high frequencies of Ostertagia-specific cells in PBL, and that after infection these frequencies decrease. These results indicate either active suppression of the potential anti-Ostertagia response or an extra-vascularization of these cells to the site of infection.

Animals↗
PubMed2001

Serum acid phosphatase level and biochemical recurrence following radical prostatectomy for men with clinically localized prostate cancer.

OBJECTIVES: Serum acid phosphatase (ACP) was once used as the marker for advanced prostate cancer. However, with the development of assays for prostate-specific antigen (PSA), a more sensitive and specific tumor marker, the use of ACP has diminished. We investigated the prognostic value of preoperative serum ACP in predicting prognosis for men with localized prostate cancer following radical retropubic prostatectomy (RRP). METHODS: Of 2293 men treated from 1982 to 1998, 1681 men had a preoperative ACP measurement using an enzymatic assay. We analyzed the actuarial freedom from biochemical (PSA) progression following RRP according to ACP levels. We used multivariate logistic regression and proportional hazards models to determine the independent prognostic value of ACP level with respect of pathologic stage and biochemical recurrence. RESULTS: ACP was not an independent predictor of organ confinement or lymph node involvement in the multivariate logistic regression models using preoperative variables. However, in the proportional hazards model, ACP was an independent predictor of tumor recurrence following RRP, and there was a statistically significant improvement in biochemical recurrence-free survival for men with lower levels of ACP (P <0.001). Furthermore, the normalized hazard ratios of ACP and PSA for predicting biochemical recurrence were similar. CONCLUSIONS: Stratification of men according to their preoperative ACP levels was predictive of patient outcome after RRP. Proportional hazards modeling using preoperative variables demonstrated that the serum ACP level is an independent predictor of tumor recurrence following RRP.

Acid Phosphatase↗
PubMedDate not supplied

Biologically relevant orthotopic neuroblastoma xenograft models: primary adrenal tumor growth and spontaneous distant metastasis.

To provide investigative tools for the study of neuroblastoma (NB) biology and therapy, we have characterized five orthotopic (adrenal) human xenograft models of NB. Initial experiments compared subcutaneous (heterotopic) with adrenal (orthotopic) injections of two NB cell lines (SK-N-AS and SMS-KCNR) in Beige-SCID mice. These studies demonstrated more relevant tumor biology, including angiogenic phenotype, and enhanced spontaneous distant metastasis for orthotopic versus heterotopic tumors. RNase protection assay demonstrated differences in the expression of angiogenesis-associated genes (flt1, TIE1, angiopoietin, and endoglin) between adrenal and subcutaneous xenografts. Orthotopic models were used to define and characterize the three remaining NB cell lines (SH-SY5Y, LA-1-15N, and IMR32). The pattern of angiogenesis was distinctive for each xenograft model and included a variety of vascular structures. The sites for metastases were distinct for each cell line and included lymph nodes, liver, ovaries, lungs, bone marrow and local bone extension. These well characterized, relevant, highly angiogenic, and metastatic orthotopic models of NB will be a valuable resource to improve our understanding of the biology and treatment of NB.

Adrenal Gland Neoplasms↗
PubMed1990

Immunohistochemical expression of c-erbB-2 in human breast cancer by monoclonal antibody: correlation with lymph node and ER status.

c-erbB-2 Protein expression was investigated in a series of fifty primary breast cancers by means of a specific monoclonal antibody and immunocytochemistry. Specific staining was observed at the plasma membrane level of neoplastic cells, according to the reported localization of c-erbB-2 protein. Sixty-four percent of tumors scored positive, with a variable amount of stained cells. The rate of protein expression was found to exceed the reported gene amplification. No relationship was observed between c-erbB-2 protein staining and age, menopausal status or histologic subtypes. An inverse association was found between c'erbB-2 protein staining and estrogen receptor content of tumors, assayed by immunocytochemistry. A positive relationship was observed between c-erbB-2 protein expression and presence of axillary node metastasis. These findings suggest that c-erbB-2 protein expression is a marker of tumor aggressiveness and that its prognostic power deserves further investigation both in node-positive and node-negative patients.

Adult↗