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PubMed2002

p53 and DCC immunohistochemistry in curative rectal cancer surgery.

BACKGROUND AND AIMS: In rectal cancer altered expression of p53 or DCC may be indicative of poor patient prognosis. This study determined by immunohistochemistry the tumour status of p53 protein and DCC protein in patients with rectal cancer who had a curative resection and were followed-up prospectively and examined the correlation to clinical and pathology variables. PATIENTS AND METHODS: The study included 171 who had a curative resection for rectal cancer: 88 at Concord Hospital (CH) followed up for a mean of 11 years and 83 at Royal Prince Alfred Hospital (RPAH) followed up prospectively for a mean of 4.3 years. Specimens were assessed by immunohistochemical assay of p53 expression ( n=170) and of DCC expression ( n=168). RESULTS: p53 over-expression was demonstrated in 58% of CH tumours and 59% of RPAH tumours. Absence of normal DCC expression was demonstrated in 66% of CH tumours and 52% of RPAH tumours. On both separate and combined analysis of these groups there were no significant associations by univariate analysis between p53 expression or DCC expression or combinations of p53 and DCC expression and the pathology variables: extent of penetration through bowel wall, lymph node involvement, presence of venous invasion, and tumour differentiation. CONCLUSION: The immunohistochemical p53 and DCC status of rectal tumours was not associated with other clinical or pathology variables, nor predictive of outcome.

Cell Adhesion Molecules↗
PubMed1999

Nasal-associated lymphoid tissue: phenotypic and functional evidence for the primary role of peripheral node addressin in naive lymphocyte adhesion to high endothelial venules in a mucosal site.

Nasal-associated lymphoid tissue (NALT), a mucosal inductive site for the upper respiratory tract, is important for the development of mucosal immunity locally and distally to intranasally introduced Ag. To more fully understand the induction of nasal mucosal immunity, we investigated the addressins that allow for lymphocyte trafficking to this tissue. To investigate the addressins responsible for naive lymphocyte binding, immunofluorescent and immunoperoxidase staining of frozen NALT sections were performed using anti-mucosal addressin cell adhesion molecule-1 (MAdCAM-1), anti-peripheral node addressin (PNAd), and anti-VCAM-1 mAbs. All NALT high endothelial venules (HEV) expressed PNAd, either associated with MAdCAM-1 or alone, whereas NALT follicular dendritic cells expressed both MAdCAM-1 and VCAM-1. These expression profiles were distinct from those of the gut mucosal inductive site, Peyer's patches (PP). The functionality of NALT HEV was determined using a Stamper-Woodruff ex vivo assay. The anti-L-selectin MEL-14 mAb blocked >90% of naive lymphocyte binding to NALT HEV, whereas the anti-MAdCAM-1 mAb, which blocks almost all naive lymphocyte binding to PP, minimally blocked binding to NALT HEV. NALT lymphocytes exhibited a unique L-selectin expression profile, differing from both PP and peripheral lymph nodes. Finally, NALT HEV were found in increased amounts in the B cell zones, unlike PP HEV. These results suggest that NALT is distinct from the intestinal PP, that initial naive lymphocyte binding to NALT HEV involves predominantly L-selectin and PNAd rather than alpha4beta7-MAdCAM-1 interactions, and that MAdCAM-1 and VCAM-1 expressed by NALT follicular dendritic cells may play an important role in lymphocyte recruitment and retention.

Animals↗
PubMed2001

Locoregional treatment of low-grade B-cell lymphoma with CD3xCD19 bispecific antibodies and CD28 costimulation. I. Clinical phase I evaluation.

We describe the first clinical application of T-cell-recruiting bispecific antibodies directly into the tumor without the need to preactivate the effector cells. In a Phase I clinical trial, 10 patients with low-grade B-cell lymphoma were treated by a single locoregional injection of CD3xCD19 bispecific antibodies. Costimulatory signaling, which is required for the optimal activation of resting T cells, was provided by the simultaneous administration of CD28 antibodies. Equal amounts of both antibodies were injected together at 4 different dose levels (30 microg: 3 patients; 270 microg: 3 patients; 810 microg: 3 patients; 1,600 microg: 1 patient). The injection was well tolerated with mild to moderate adverse effects (2/10 patients) consisting of erythema and fever at the third dose level. The maximum tolerated dose was not reached at 810 microg of injected antibodies. Three patients showed a serum peak of TNFalpha on day 2 or 3 after the antibody application, reflecting rather an activation of CD4-positive T cells than an FcR-mediated effect. Five patients developed anti-mouse antibodies after injection of the murine immunoglobulins. Nine patients were evaluable for restaging examinations 6 weeks after the antibody application, with 2 of them (22%) showing a local clinical response. We found that a single locoregional injection of CD3xCD19+CD28 antibodies is feasible up to a dose of at least 1,600 microg of each antibody. However, the development of human anti-mouse antibodies points toward the requirement for new formats of bispecific proteins with reduced immunogenicity.

Aged↗
PubMed1981

Ceruloplasmin assays in diagnosis and treatment of human lung, breast, and gastrointestinal cancers.

Ceruloplasmin was assayed as enzyme activity, as antigen, and as total copper in serum samples from 150 male lung cancer patients and comparable numbers of male controls. By all three assays, ceruloplasmin was significantly increased above the normal before treatment, and the degree of elevation was related to TNM stage [i.e., the International Union Against Cancer classification system based on extent of primary tumor (T), condition of lymph nodes (N), and absence of presence of metastases (M)]. Surgery had no immediate effects, but in patients who evidence of disease for longer periods, ceruloplasmin returned to nearly normal values. High levels of ceruloplasmin was elevated in 6 of 9 patients before tumor recurrence; 2 of 3 smokers (in the first panel of sera) with elevated ceruloplasmin levels subsequently developed lung cancer. The relative merits of the three assays were compared. Some sex- and age-related differences among normal controls were apparent. The results of pilot studies on men with gastrointestinal cancer and women with breast cancer are presented. It is concluded that only in limited situations will assays of ceruloplasmin aid in diagnosis, prognosis, and long-term monitoring of cancer patients.

Adult↗
PubMed2000

HER-2/neu gene amplification by FISH predicts poor survival in Barrett's esophagus-associated adenocarcinoma.

The HER-2/neu oncogene is localized to chromosome 17q and shares significant homology with the epidermal growth factor receptor. HER-2/neu protein overexpression has been associated with poor prognosis in a variety of tumors, but its significance in Barrett's esophagus-associated adenocarcinoma (BEAd) is unknown. Therefore, the aim of this study was to evaluate the prevalence and prognostic value of HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) in 63 cases of BEAd. Routinely processed tissue sections from resection specimens of 63 patients with BEAd (M/F ratio, 10:1; mean age, 63 years) were assayed for HER-2/neu gene amplification by FISH using the Ventana unique sequence probe (Ventana Medical Systems, Inc, Tuscon, AZ). FISH results were correlated with the pathological features of the tumors and with patient survival. Clinical follow-up data were available for 54 patients (mean follow-up, 31 months [range, 1 to 152 months]). The HER-2/ neu gene was amplified in 12 of 63 (19%) cases. The presence of HER-2/neu gene amplification showed a trend toward a correlation with depth of tumor invasion (P = .07), lymph node metastasis (P = .13), and pathological stage (P = .14), but did not correlate with any of the other pathological features, such as degree of differentiation or tumor size. On both univariate and multivariate analysis, HER-2/neu gene amplification was associated with shortened survival (P = .03). HER-2/neu oncogene amplification, as determined by FISH, correlates with shortened patient survival and independently predicts poor outcome in patients with BEAd.

Adenocarcinoma↗
PubMed1975

Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes.

A systemic graft-vs.-host (GVH) reaction was initiated by the intravenous injection of parental strain thoracic duct lymphocytes (TDL) into irradiated F1 hybrid recipients with in-dwelling thoracic duct cannulae. The migration of the donor lymphocytes was followed by labeling them in vitro with either [3H] or [14C]uridine and measuring radioactivity by scintillation counting of the spleen and lymph nodes of the recipients removed 24 h after injection and in TDL collected throughout this period. The localization of labeled cells was always compared to that of a reference population of nonreactive lymphocytes, e.g. F1 hybrid, labeled with the alternative isotope (Fig. 1). A consistent surplus of the reactive label was found in the spleen which was balanced by a deficit of the reactive label in TDL; lymph nodes gave intermediate values. The same distribution pattern was noted when the reference population was a specifically unresponsive population of the parental strain. This differential distribution depends on recognition of the recipient's Ag-B antigens because when normal lymphocytes were injected together with specifically unresponsive lymphocytes into a "third party" F1 hybrid (against which both populations were reactive) there was no surplus of the normal cells in the spleen and no deficit in the lymph. Moreover in an Ag-B identical strain combination there was no detectable difference in the distribution of reactive and nonreactive populations. The distribution of a labeled reaction population can be accounted for if a substantial minority of cells are immobilized in the spleen and lymph nodes as a consequence of antigen recognition (Fig. 3). When the donor cells in the spleen were assayed 24 h after injection there was paradoxically a slight reduction in their specific GVH activity, which is at least partly because they are under-represented in a single cell suspension. The size of the splenic surplus (23%) and the thoracic duct deficit (12%) suggested that the minority of nonimmune lymphocytes which recognize each Ag-B complex carry 12% of the radioactive label in the original population. It is argued that this provides a near estimate of the frequency of T lymphocytes which can recognize each Ag-B antigenic complex.

Animals↗
PubMed1987

Possibilities of immunohistochemical investigation on human temporal bone.

After preliminary studies on human tonsillar tissue, lymph node tissue, or tissue from the appendix, it could be shown that after a fixation in Bouin solution or in sublimate-formaldehyde solution and subsequent embedding of the tissue in paraffinwax, the structure of the immunoglobulins present in the tissue remains intact. Even after long-term decalcification of the fixed tissue in EDTA, its structure does not alter and the immunoglobulins can be detected in high dilution either by the direct immunofluorescence method or with peroxidase-antiperoxidase. Human temporal bones from healthy individuals were fixed in Bouin solution or in sublimate-formaldehyde solution and incubated for sufficient time in EDTA decalcification solution until they were radiologically free of calcium. After embedding in paraffinwax or Paraplast, the immunoglobulins of the middle ear mucosa could be identified with the immunohistochemical methods described above. For the first time, localized immunoglobulins including the secretory component in the endolymphatic sac could also be demonstrated. The method is so sensitive that the binding of antibodies from the serum of patients with possibly immunopathological inner ear conditions can be detected by means of the indirect immunofluorescence test. Furthermore, other immunohistochemical assay methods can also be carried out with these methods (e.g. neuropeptide detection.

Decalcification Technique↗
PubMed1995

Humoral and cellular responses following local immunization with a surface antigen of the gastrointestinal parasite Haemonchus contortus.

A purified, larval specific antigen of the abomasal parasite Haemonchus contortus was used to immunize sheep. In an attempt to induce a local immune response in the abomasum, the antigen was injected twice into the abomasal wall after one peripheral immunization. Serum antibody responses were boosted by each intra-abomasal immunization but not by the challenge infection given 3.5 weeks after the last immunization. Examination of the specific antibody secreting cells (ASC) recirculating in the peripheral blood indicated that there was an increase in blood ASC 5 days after local stimulation. This increase was maintained only after immunization and not after infection, probably reflecting the different responses induced when antigen is presented by injection in an adjuvant or by the parasite during infection. High proliferative T cell responses in the abomasal lymph nodes were only observed in one of the five sheep immunized with antigen; this was also the only sheep in this group to maintain an adult parasite burden at postmortem corresponding with the lowest antibody response. Peak faecal egg counts after infection were reduced by 54% in the immunized group compared to control sheep. Egg counts in the control sheep were, however, variable and dropped quickly, probably as a consequence of the inflammatory response induced by the injection of aluminium hydroxide into the abomasal wall.

Abomasum↗
PubMed1983

Abrogation of epidermal antigen-presenting cell function by ultraviolet radiation administered in vivo.

The exposure of animals to ultraviolet radiation (UVR) can result in dramatic alterations to their immunologic potential. Loss of ability to be contact-sensitized to skin-reactive chemicals applied to UVR-exposed surfaces, and an enhanced susceptibility to tumors induced by UVR represent two well-documented effects of such exposure. The skin Langerhans' cell (LC) is a cell type, having antigen presentation capabilities, which is functionally inactivated by UVR. The localized loss in the ability to induce a contact hypersensitivity (CS) response and the early events associated with the acquisition of a tumor-susceptible state have been hypothesized to involve LC inactivation by UVR. In this report we have investigated the relationship between the UVR-mediated loss of CS responsiveness and antigen-presenting cell (APC) function by LC following in vivo exposure of animals to UVR. The UVR-mediated loss of CS responsiveness was found to be both time-dependent and dosage-dependent, but the loss of epidermal APC function following the UVR exposure of dissociated epidermal cells or skin was immediate and dosage-dependent. The lack of time dependency associated with the loss of epidermal APC function may be due to the nature of the assay system being employed. Add-back experiments, using the proliferation of purified antigen-primed T-cells as a read-out system to evaluate APC function, require that the accessory cell be totally functional. Initiation of CS responses may still be possible, however, with LC that are partially UVR-inactivated. Lymph-node-associated and circulating accessory cells could be integrated into the response, providing any necessary components that the UV-inactivated LC lacks. We tested this possibility and conclude from these studies that this is indeed a viable possibility. Our results, therefore, provide a possible explanation for apparent differences in LC UVR susceptibility observed when in vitro and in vivo assays are employed.

Animals↗
PubMed2004

Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression.

The prognostication of head and neck squamous cell carcinoma (HNSCC) is largely based upon the tumor size and location and the presence of lymph node metastases. Here we show that gene expression patterns from 60 HNSCC samples assayed on cDNA microarrays allowed categorization of these tumors into four distinct subtypes. These subtypes showed statistically significant differences in recurrence-free survival and included a subtype with a possible EGFR-pathway signature, a mesenchymal-enriched subtype, a normal epithelium-like subtype, and a subtype with high levels of antioxidant enzymes. Supervised analyses to predict lymph node metastasis status were approximately 80% accurate when tumor subsite and pathological node status were considered simultaneously. This work represents an important step toward the identification of clinically significant biomarkers for HNSCC.

Adult↗
PubMed2003

Association of ets-related transcriptional factor E1AF expression with tumour progression and overexpression of MMP-1 and matrilysin in human colorectal cancer.

Expression of E1AF/PEA3 (ETV4), an ets family transcription factor, has been implicated in the invasive potential of several cancer cell lines through induction of matrix metalloproteinase (MMP) expression. The aim of this study was to examine E1AF mRNA expression and to determine whether it is correlated with progression of, and/or MMP expression in, human colorectal cancer. Using the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), 100 colorectal cancer tissues were analysed for E1AF mRNA expression. Expression of ER81 (ETV1) and ERM (ETV5), the other two members of the PEA3 subfamily, and Ets-1 and Ets-2 was also analysed. The results were correlated with clinicopathological characteristics and MMP expression. Immunohistochemical analysis and an in vitro invasion assay were also performed. E1AF mRNA expression was detected in 62% of the 100 colorectal cancer tissues, but was undetectable or only faintly detected in adjacent non-tumour tissues. E1AF mRNA was detected in all of the ten liver metastases from colorectal cancers. E1AF expression correlated significantly with depth of invasion, lymphatic and venous invasion, lymph node and distant metastasis, advance in pathological tumour-node-metastasis stage, and recurrence. Patients with E1AF-positive tumours had significantly shorter overall and disease-free survival periods than did those with E1AF-negative tumours (p < 0.0001 and p < 0.0001, respectively). E1AF expression retained its significant predictive value for overall and disease-free survival in multivariate analysis that included conventional clinicopathological factors (p = 0.0066 and p = 0.0109, respectively). Among the MMPs analysed, expression of MMP-1 and matrilysin correlated significantly with E1AF expression. In contrast, expression of ER81 and ERM did not correlate with clinicopathological characteristics or the expression of these MMPs. Immunohistochemical expression of E1AF was predominantly observed at the invasive front, where the expression of MMP-1 and matrilysin and nuclear beta-catenin expression were often co-localized. Antisense E1AF-transfected HT-29 colon cancer cells expressed reduced levels of MMP-1 and matrilysin and were less invasive in vitro than neo-transfected HT-29 cells. The results of this study suggest that E1AF, the expression of which is closely correlated with the expression of MMP-1 and matrilysin, plays a key role in the progression of colorectal cancer.

Adenocarcinoma↗
PubMed1999

[Cytokine expression of transforming growth factor-beta2 and interleukin-10 in squamous cell carcinomas of the head and neck. Comparison of tissue expression and serum levels].

Transforming growth factor-beta (TGF-beta) and interleukin 10 (Il-10) are cytokines that have a strong immunosuppressive ability. Their secretion by tumor cells is able to suppress an immunological response against tumor. Both factors have been shown to enhance tumor growth in glioblastomas and carcinoma of the breast. We determined the expression pattern of TGF-beta and Il-10 in squamous cell carcinomas of the head and neck (HNSCC) and a possible association with tumor stage and their pre-treatment cytokine serum levels. Cytokine expression in primary tumors and metastases of 21 patients with HNSCC was investigated by immunohistochemistry. To assess the TGF-beta2 and Il-10 levels in tumor patients before therapy 49 serum specimens were analyzed by ELISA. TGF-beta2 was detected in 95% of all tumor tissues analyzed and Il-10 in 79% of all tumors. TGF-beta2 was localized in tumor cells and tumor borders, while Il-10 was preferentially found in peritumoral connective tissue. Metastasizing tumors showed elevated pretreatment serum levels for TGF-beta2 and Il-10. There was no correlation between TGF-beta2 and Il-10 expression in tumor tissue and pretreatment serum levels. Our data show that the majority of HNSCC analyzed express TGF-beta2 and Il-10. A correlation between pretherapy elevated cytokine serum levels and tumor grade was shown.

Biopsy↗
PubMed1988

Induction by cells of immune responses to intestinal epithelial cell-associated components (ECAC): transfer with cultured murine mesenteric and popliteal/axillary lymph node cells.

Although systemic and mucosal immune responses to intestinal epithelial self-antigens occur in several human disorders, there is no model system with which to study the physiology and regulation of the underlying cellular events. Therefore, we undertook to induce an immune response to purified epithelial macromolecules in the Lewis rat; characterize in vitro the reactive cells; and then transfer with immunocytes this antiepithelial reactivity to naive syngeneic rats, identifying the fine specificity and site of humoral and cell-mediated immunity induced in the cell recipient. Donor animals sensitized systemically (via footpad) or locally in gut mucosa (via Peyer's patches) to syngeneic or xenogeneic epithelial antigens generated specific immunoglobulin and were found to have T lymphocytes in the draining nodal areas (including the mesenteric nodes) which were (a) antigen-specific, having a [3H]thymidine uptake in the presence of antigen 30-fold the control; (b) generally of the Thelper/inducer subclass (W3/25+) which, upon further culture, developed phenotype surface markers for activation (IL-2R+); (c) able to induce an antigen-specific humoral and cell-mediated responses upon intravenous injection into naive syngeneic hosts; and (d) demonstrable in gut-associated lymphoid tissue (mesenteric lymph nodes) and, to a lesser extent in spleen, of the cell recipient. Further, lymphocytes cloned from reactive mesenteric lymph node cells demonstrated specificity for a gel-purified subfraction of epithelial antigen, designated P1, containing highly conserved organ-specific macromolecules thought to be autoantigenic for gut.

Animals↗
PubMed2005

Tumour-associated urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in normal and neoplastic tissues of patients with squamous cell cancer of the oral cavity - clinical relevance and prognostic value.

The central role of the serine protease urokinase-type plasminogen activator (uPA) and its inhibitor, the plasminogen activator-inhibitor-1 (PAI-1), in tumour invasion and metastasis becomes more and more evident. In several studies, uPA and PAI-1 proved to be of prognostic relevance as shown for different types of cancer (e.g. breast, stomach, lung). Elevated antigen levels of uPA and/or PAI-1 predict poor outcome (relapse-free survival) for patients afflicted with cancer. For oral squamous cell carcinomas, however, the prognostic relevance of the tumour-associated proteolytic factors uPA and PAI-1 has still to be evaluated. In the present study, using tissue extracts of 79 oral cancer cases, 58 specimens of normal oral cavity mucosa and of 16 tumour positive lymph nodes taken from the same patients, uPA and PAI-1 antigen were determined by highly sensitive enzyme-linked immunosorbent assays (ELISA). A correlation was found between uPA and PAI-1 in tumour tissue, when compared with the normal mucosa of the same oral cavity. Median levels showed significant elevations in cancer tissue and in tumour positive lymph nodes versus normal oral mucosa. In patients with high levels of uPA or PAI-1, there were significantly more tumour relapses. There was no significant correlation between pathological TNM categories, grading, residual tumour category, tumour site and patient age. In summary, tumour uPA/PAI-1 content (as determined by ELISA) appears to be a strong independent prognostic factor for relapse-free survival in squamous cell cancer of the oral cavity. These observations might help to select patients with poor prognosis for additional adjuvant therapy in conjunction with complete surgical resection.

Disease-Free Survival↗
PubMed1990

New concepts in the treatment of stage D1 adenocarcinoma of the prostate.

Stage D1 disease will be encountered in 20 per cent of patients by those who treat prostate cancer. There is marked heterogeneity among cancers discovered at this stage, with 5-year disease-free survival rates ranging from 0 to 95 per cent. Generally, when prostate cancer has escaped the confines of the gland, metastasis occurs, and widespread systemic disease prevails. Any significant chance for long-term cure will then depend on systemic therapy. From maturing data in retrospective reviews, preliminary data from prospective trials, and recent well-conducted animal studies, chemotherapy and hormonal deprivation appear most effective when tumor volumes are the smallest. This evidence supports the removal of all cancer possible and the early institution of systemic treatment. Caution must be exercised in extrapolating the aforementioned evidence to include cases of more extensive prostate cancer (i.e., patients with bulky pelvic or retroperitoneal disease, distant metastasis, or significant elevation of serum markers). It is doubtful that "debulking" with removal of the prostate and lymph nodes will provide any justifiable advantages in these patients. Whether removal of the prostate affords any local palliative benefit is an issue for debate. Certainly, the primary tumor, if left untreated, will progress locally and cause symptoms necessitating further procedures in more than half these patients, whereas the incidence of local recurrence and the adverse effects of these recurrences in patients with D1 disease after radical prostatectomy and adjuvant therapy is less than 10 per cent. Surgical refinements coupled with acceptably low morbidity now associated with radical prostatectomy have led some authors to endorse the palliative benefits of removing the primary tumor in selected patients. The purpose of this article is not to endorse or disparage the aggressive treatment of patients with stage D1 prostate cancer. The evidence suggests that if long-term survival is the endpoint used to compare treatment groups, then to date no treatment option offers significant advantages. On the contrary, if progression rates or disease-free survival are compared, then cytoreductive surgery and early systemic adjuvant treatment (testosterone deprivation or chemotherapy) provides significant advantages for selected patients with stage D1 disease. Although ploidy analysis, receptor mapping, and oncogene assays are promising, today, there is no practical way to identify patients who will benefit most from multimodality treatment approaches.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1982

Effect of time and therapy on the hormone receptor status of breast carcinomas.

To determine whether the hormone receptor status of a breast carcinoma can change during the course of the disease or its treatment, the results of estrogen receptor assays in two or more biopsy specimens from 68 patients were examined; progesterone receptors had been assayed in approximately 40% of the specimens, too few to permit statistical analysis of the results. The patients fell into four groups: A, those with at least two primary breast carcinomas, and B to D, those with at least two breast carcinomas, at least one of which was a secondary tumour (usually of lymph node, skin or soft tissue) excised on the same occasion (B), 1 to 76 months later, after no intervening therapy (C), or 3 to 73 months later, after intervening chemotherapy (usually adjuvant), regional irradiation or hormonal therapy, or a combination of these (D). The small numbers in the subgroups precluded statistical analysis of the results for groups A and D. The degree of concordance of the hormone receptor status of the primary and secondary tumours in groups B and C was significant, at 87% (P less than 0.01) and 80% (P congruent to 0.01) respectively. Chemotherapy and regional irradiation did not appear to reduce the degree of concordance. All primary tumours in the same breast removed on the same occasion had the same hormone receptor status, but bilateral primary tumours appeared to have an independent status, which suggests that local tissue factors, as well as the systemic hormonal environment, play a role in establishing the hormone receptor status of breast carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1980

The relationship between cytotoxicity and prognostically significant histologic changes in lymph nodes from patients with cancer of the breast.

Axillary lymph nodes obtained from 37 patients with cancer of the breast were used in a microcytotoxicity assay against a human mammary cancer cell line, ALAB. Cell suspensions made from 60 individual lymph nodes and 51 lymph node pools were tested. Each lymph node was graded for the extent of the histologic changes of sinus histiocytosis (SH), paracortical hyperplasia (PCH), and germinal center hyperplasia (GCH). High levels of cytotoxicity correlated significantly with the presence of SH and PCH. When multiple lymph nodes of individual patients were pooled and tested, a high intensity of GCH correlated with a low degree of cytototoxicity. The cytotoxic activity of pooled lymph nodes from different axillary regions was studied in 20 patients. In 7 of these patients, low axillary lymph node cells were more cytotoxic than high axillary node cells. The reverse was found for 7 patients, and there was no difference in cytotoxicity between axillary regions in 6. Cytotoxic lymph node pools had high SH and low GCH whether they were obtained from the low or high region. Noncytotoxic lymph node pools from the high axillary region had a low intensity of all three histologic reactions. In contrast, noncytotoxic lymph node pools from the low axillary regions had high intensities of SH, PCH, and GCH. These results suggest that germinal center hyperplasia in the lymph nodes nearest an advancing tumor is associated with a local suppression of cytotoxic cell activity.

Adult↗
PubMed1994

Primary infection of dogs with Echinococcus granulosus: systemic and local (Peyer's patches) immune responses.

Local and systemic lymphocyte proliferation and antibody production were tested in five dogs 35 days after primary experimental infection with Echinococcus granulosus. A significant cell proliferation was demonstrated by [3H] thymidine incorporation in mesenteric, popliteal and/or Peyer's patches (PPs) cells in response to E. granulosus protoscolex or adult worm antigen in three of five infected dogs, but not in five control animals. In contrast, blood mononuclear cells responded very weakly in only two of the infected dogs to parasite antigens. Elevated levels (compared with preinfection status) of protoscolex- and adult worm antigen-specific serum IgG were detected (ELISA) in four of the five dogs 35 days after infection. Furthermore, slightly elevated levels of parasite-specific IgE and IgA were observed in the sera of three and four in four infected dogs, respectively. Specific serum IgM was not significantly higher 35 days after infection than before infection. Local antibody production was studied in vitro using PPs, mesenteric and popliteal cells isolated from three infected and three uninfected dogs by ELISA using adult worm antigen. In two of three cultures of unstimulated PPs cells of infected dogs, parasite-specific IgG was detectable. Parasite-specific IgA and IgM were detected in one of the unstimulated PPs cell culture derived from an infected dog. Following in vitro stimulation with parasite antigen, PPs cells from two infected dogs showed increased parasite-specific IgG and PPs cells of all three infected dogs produced parasite-specific IgA. PPs cells from uninfected dogs did not produce significant quantities of parasite-specific antibodies and cells from mesenteric and popliteal lymph nodes of infected or uninfected dogs neither produced antibodies whilst in in vitro cultures.

Animals↗