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PubMed1989

Recovery of activated cytotoxic T cells from minor H incompatible tumor graft rejection sites.

In this study we determined whether minor H-specific cytotoxic T cells and their precursors (pTc) are present at the site of rejection of minor H disparate tumor allografts. Lymphocytes were retrieved from eyes of BALB/c mice that received subconjunctival injections of minor H-incompatible P815 tumor cells. The lymphocytes were then assayed for direct cytotoxic activity as well as precursor frequency by limiting dilution. Similar assays were conducted on cells obtained from the draining lymph nodes and from the spleen. As expected, tumor rejection was accompanied by significant clonal expansion of minor H-specific pTc within the draining lymph node and the spleen. A correspondingly high frequency of pTc was also detected at the graft site. More importantly, fully functional cytotoxic T cells were recovered from the tumor graft site during rejection, but no similarly active cells were found in either the draining nodes or spleen. We conclude that, after Ag stimulation, pTc are generated in draining central lymphoid compartments. From this generative site, the precursor cells then disseminate systemically, gradually reaching and infiltrating the tumor graft site. A further activation step, dependent upon Ag and T cell help, permits these cells to mature into fully active cytotoxic cells which can then effect tumor rejection. We propose that the terminal stage(s) of pTc activation is promoted by lymphokines released locally from TDH cells that are also generated during the alloimmune response and simultaneously infiltrate the site.

Animals↗
PubMed1978

Cellular changes in lungs of mice infected with influenza virus: characterization of the cytotoxic responses.

Transpleural lavage of lungs from uninfected C3H mice yielded an average of 300,000 leukocytes per mouse. This number increased eightfold within 6 days after intranasal inoculation with virulent influenza A/Hong Kong/68 (H3N2) virus. Macrophages and lymphocytes in approximately equal numbers comprised 90% or more of the leukocytes both before and during infection. B, T, and null lymphocytes comprised, respectively, 9, 21, and 18% of the leukocytes before infection and 7, 26, and 5% by day 6. In absolute numbers, macrophages and T lymphocytes provided the major increments during infection. Cytotoxic activity of mononuclear cells from lung lavages was compared in a chromium release assay using syngeneic L929 target cells with the activity of mediastinal lymph nodes, spleens, and peripheral blood of uninfected and infected C3H mice. Nonspecific cytotoxicity for target cells infected with H3hkNeq1 or B/Lee influenza virus was found with mononuclear cells from uninfected mice. This activity tended to be highest with lavage leukocytes and was associated with adherent cells, presumably macrophages. Increased virus-specific cytotoxicity was detected with lavage cells by day 6 and persisted through day 9, the period of maximal pneumonia. Similar cytotoxic activity also appeared in cells from the nodes and spleen at this same time but was not detected in peripheral blood cells. The virus-specific cytotoxicity of lavage cells was due largely to a nonadherent cell possessing Fc receptors and theta antigen but lacking C3 receptors; these properties are compatible with actively cytotoxic T lymphocytes. The cytological characteristics of the infiltrating leukocytes and the cytotoxicity data suggest that the local T cell response to influenza virus infection in the lung is a major contributor to the pneumonia observed in this mouse model.

Animals↗
PubMed2004

Metachronous breast carcinoma (second malignancy), following "cure" from colorectal carcinoma.

Metachronous or synchronous breast carcinoma following or co-existing with colorectal carcinoma are well recognised clinicopathological entities, and the risk of developing both possibly underlines the similarities in carcinogenesis pathways for these carcinomas. We present a 60-year-old housewife with a history of a treated primary colon carcinoma (Duke's C) 15 years previously. Six months ago, during the follow-up care a small sub-areolar lesion was determined in a mammogram. A lumpectomy was performed under local anaesthesia, which revealed an infiltrating ductal carcinoma (6 mm in greatest diameter). Immuno-histochemical assays for oestrogen and progesterone receptors and c-erb B2 ongoprotein were performed. Axillary lymphadenectomy showed 1/11 positive node. She received adjuvant radiotherapy and hormone manipulation. To date, seven months later she is disease free. The aim of this report is to emphasise the risk of metachronous second malignancy of breast or colorectal carcinoma following colorectal carcinomas. A second primary colonic malignancy following breast primary carcinoma is more frequent than inverse clinical form.

Adenocarcinoma↗
PubMed1988

Multiparametric study (SAMBA 200) of estrogen receptor immunocytochemical assay in 400 human breast carcinomas: analysis of estrogen receptor distribution heterogeneity in tissues and correlations with dextran coated charcoal assays and morphological data.

Estrogen receptor (ER) immunocytochemical assay (ER-ICA) was assessed in 400 human breast carcinomas. In all cases, patient's age, tumor size, histological type and Scarff-Bloom-Richardson grade, and presence or absence of axillary lymph node metastases and of vessel invasion in tumor borders were recorded. In 310 cases estrogen and progesterone receptors were concomitantly evaluated (dextran coated charcoal method). In 60 of these cases the ER immunoenzymatic assay (ER-IEA) was also assessed. Monoclonal H222sp gamma and peroxidase antiperoxidase procedures (Abbott kit) were applied in frozen sections, tumor imprints, and fine-needle aspirates. A computerized system of image analysis referred to as SAMBA (TITN), permitted a multiparametric quantitative analysis of ER-positive surfaces. With this system, in each tumor, the cellularity, percentage of ER surface versus the total cell surface and versus the epithelial (keratin-positive) surface, integrated optical density, mean optical density, index of the concentration of labeled objects, and integrated optical density histograms, were obtained and correlated to histological and biochemical data. It was shown that (a) ER antigenic sites were heterogeneously distributed in ER-positive tumors, with a specific nuclear localization in epithelial cells; (b) SAMBA 200 multiparametric analysis of the ER sites distribution in tissue was appropriate, accurate, reproducible, and therefore more reliable than the semiquantitative analysis; (c) standardization and complete automation of this method of immunoprecipitates evaluation on tissue section permits daily and routine analysis of a large number of preparations; (d) there was a correlation between ER binding sites evaluation (dextran coated charcoal) and ER antigenic sites immunodetection (ER-ICA and ER-IEA); (e) there was a correlation between the SAMBA evaluation of ER-ICA and other histological prognostic factors such as small tumor size, low Scarff-Bloom-Richardson grade; (f) the preliminary SAMBA analysis of ER-ICA in tissue sections, imprints, and fine needle aspirates suggest that fine needle aspirates may not reflect accurately the tumor cell heterogeneity.

Breast Neoplasms↗
PubMed1988

Active specific immunotherapy for melanoma: phase I trial of allogeneic lysates and a novel adjuvant.

A Phase I trial of active specific immunotherapy for melanoma was performed to measure the toxicity and immunological effects of the therapy. A mixture of mechanical lysates (homogenates) of two melanoma cell lines was injected together with a novel adjuvant, DETOX, into 22 patients. Several types of cell-mediated and humoral immunity to melanoma-associated antigens were measured serially. In the 17 patients with measurable disease, the sizes of lesions were also noted serially. At least six patients per group were injected s.c. with either 100, 200, or 400 antigenic units (approximately 10, 20, and 40 million tumor cell-equivalents) of the lysates mixed with 0.25 ml of DETOX s.c. on weeks 1, 2, 3, 4, and 6. Three patients at each dose level also received 300 mg/m2 of cyclophosphamide i.v. 4 days before the start of immunization. Evidence for successful immunization was obtained in 13 of the 22 patients. An increase in the frequency of peripheral blood cytolytic lymphocyte precursors reacting against melanoma cells occurred in 12 patients, as measured by a limiting dilution assay involving in vitro re-exposure to irradiated melanoma cells for 9-10 days. Eight of the 12 patients had received cyclophosphamide. By cold-target competition assays, these cytolytic lymphocytes appeared to be atypical T-cells, which recognized melanoma-associated antigens on several allogeneic lines without apparent major histocompatibility complex restriction. An increase in antibody titers against melanoma-associated antigens, measured by enzyme immunoassay, was found in five of 22 patients, and a change in delayed hypersensitivity against the melanoma lysate, in three patients. Responses were found at all three dosage levels of lysate, without an obvious dose optimum. No toxicity except minor local soreness was noted. Therefore, no maximum tolerable dose was defined. Five of 17 patients with measurable lesions had a remission of their melanoma, two complete and three partial, with three additional minor responses. A patient whose complete remission lasted 5.5 months, has no evidence of disease 22+ months after entry onto the study, with the aid of surgical resection of small s.c. recurrences on two separate occasions. Sites of regression included s.c. nodules, lymph nodes, and pulmonary nodules, with no responses in liver, adrenal gland, or bone. The patients who had an increase in cytolytic lymphocyte precursors comprised all eight with a clinical remission (five major, three minor). In contrast, none of the seven patients lacking an increase in cytotoxic lymphocytes had a clinical response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMedDate not supplied

Peripheral sympathetic denervation alters both the primary and memory cellular immune responses to herpes simplex virus infection.

Numerous studies have sought to delineate the impact of neuroendocrine function on overall immune responsiveness. Using various murine models, we and others have previously shown that both adrenal-dependent and adrenal-independent mechanisms associated with psychological stress modulate components of both the primary and memory cellular immune responses to herpes simplex virus type 1 (HSV-1) infection. We have extended these studies by determining the impact of 6-hydroxydopamine (6-OHDA)-mediated peripheral sympathetic denervation on both responses. C57BL/6 mice treated with 6-OHDA (200 mg/kg) exhibited reduced generation of both primary lymph node- and splenic-derived cytotoxic T lymphocytes (CTL) following a local (footpad) and systemic HSV infection, respectively. 6-OHDA also suppressed activation of HSV-specific memory CTL (CTLm). In both models, alterations in cytokine production and lymphocyte subset distribution were also observed. Administration of 6-OHDA also resulted in substantial but transient activation of the hypothalamic-pituitary-adrenal (HPA) axis as was indicated by a dramatic elevation of serum corticosterone and hypothalamic Fos expression. Moreover, the corticosterone levels were directly correlated with the extent of CTLm activation. Together, these findings suggest that peripheral sympathetic denervation alters immune function through activation of the HPA axis.

Animals↗
PubMed1989

Relative importance of estrogen and progesterone receptor assays as prognostic indicators in primary breast cancer: a short-term study.

This short-term study of the relative importance of estrogen and progesterone receptors shows that progesterone receptor correlates better than estrogen receptor with tumor recurrence regardless of lymph-node status. Life-table analysis has effectively identified only two groups of patients that may be classified by progesterone receptor status alone. Progesterone-receptor negativity correlated well with tumors of histological Grade III; estrogen-receptor positivity correlated with Grade I and II tumors. The earlier recurrence of Grade III breast tumors may explain why progesterone receptor is a better prognostic indicator than estrogen receptor in short-term studies.

Breast Neoplasms↗
PubMed1985

Site-selective homing of antigen-primed lymphocyte populations can play a crucial role in the efferent limb of cell-mediated immune responses in vivo.

Lymphoid cells of the mammalian immune system exhibit special migratory properties within their in vivo environment. This fundamental characteristic is important to the protection of the organism from infection and neoplastic transformation by a process termed immunologic surveillance. The importance of lymphocyte recirculation was addressed by investigating the role of site-selective homing of lymphocytes during the efferent phase of an in vivo adoptively transferred immune response. We approached this problem by using pertussis toxin (PT), a known inhibitor of lymphoid cell migration in vivo. PT is a protein secreted by the bacterium Bordetella pertussis, which induces a selective and long-lasting inhibition of the emigration of lymphocytes from the bloodstream into solid tissue. In this study, we demonstrate that the blockade of lymphocyte extravasation potential mediates inhibition of certain cell-mediated immune responses in vivo. We investigated the effect of PT on the extravasation of antigen-primed lymphocytes into solid tissue. The results show that the loss of lymphocyte homing potential after in vitro treatment of the primed cells with PT is accompanied by an inhibition of antigen-specific contact hypersensitivity after adoptive transfer. This result suggests that the process of lymphocyte extravasation into nonlymphoid tissue sites such as the skin shares fundamental similarities to the selective localization of circulating lymphocytes to lymph nodes. Furthermore, the inhibition of contact hypersensitivity observed after the i.v. adoptive transfer of PT-treated antigen-primed cells could be circumvented by transferring the PT-treated cells directly into a tissue site with the relevant antigen. In contrast, no inhibition in the number of antibody-forming cells present within the spleen was observed after an adoptive transfer of PT-treated sheep red blood cell-primed lymphocytes, a result that is in agreement with radiotracer data. Thus, the inhibitory effect of PT on the adoptive transfer of contact hypersensitivity was established to be a direct result of the PT-mediated alteration of cellular migration, because PT inhibits the entrance of lymphocytes into specific tissue sites without inhibiting other cellular functions. This conclusion is additionally supported by experiments that showed that lymphocytes that have been pretreated with PT exhibit normal in vitro responses, as assayed by mitogenesis in response to concanavalin A and by the differentiation and function of alloantigen stimulated or hapten-specific cytotoxic T lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1981

Human thy-1: unusual localization and possible functional significance in lymphoid tissues.

BALB/c mice were immunized with purified human brain Thy-1 and used in cell fusion experiments to derive an anti-human Thy-1 monoclonal antibody. Specificity was proven by a) showing that the antigen recognized had precisely the tissue distribution expected of human Thy-1 from previous studies, and b) demonstrating that the molecule purified from human brain by monoclonal antibody affinity columns 1) had the same mobility on SDS PAGE as pure rat Thy-1 and 2) could inhibit an assay previously shown to be directed at the human-rat cross-reactive component of Thy-1. Studies with the fluorescence-activated cell sorter confirmed that Thy-1 is absent from human blood lymphocytes and cell suspensions from human lymphoid organs, except that very weak fluorescence could be detected on 7% of thymus cells in suspension. However, fluorescence studies on frozen sections showed bright staining restricted mainly to the periphery of the thymus lobule, the marginal zone and some periarteriolar lymphocytes in the spleen, and the post-capillary venules of lymph node. In some lymph nodes, a halo of Thy-1 positive cells was seen around lymphatic nodules or germinal centers, but this was not a constant finding. This distribution is different from the known distribution of Thy-1 in the lymphoid tissues of the mouse and rat. Our studies suggest that human Thy-1 might be involved in lymphocyte recirculation, and that it is a marker for early T lymphocytes in man. The studies also show that the few Thy-1 positive cells in human lymphoid organs are selectively lost in the preparation of single-cell suspensions.

Animals↗
PubMed1989

Lymphocyte entry into inflammatory tissues in vivo. Qualitative differences of high endothelial venule-like vessels in sponge matrix allografts vs isografts.

Sponge matrix allografts and isografts become extensively encapsulated and neovascularized after s.c. implantation. Sponge allografts acquire alloantigen-reactive T lymphocytes, whereas sponge isografts fail to do so, even though these T cells are continuously circulating in the peripheral blood. We have investigated the possibility that the vascular endothelia regulates lymphocytic accumulation in sponge matrix implants. In normal lymph nodes, specialized high endothelial venules (HEV) regulate lymphocyte extravasation from the blood. We have now identified HEV-like vessels in sponge matrix allografts. These vessels are operationally defined as "HEV-like" in that they react with mAb MECA 325 which identifies murine HEV, and bind lymphocytes in ex vivo adhesion assays. In contrast, sponge isografts contain MECA 325 reactive vessels that are significantly smaller than those found in allografts. Further, vessels of sponge isografts do not readily bind lymphocytes in ex vivo adhesion assays. Immunohistologic analysis also revealed that the small MECA 325+ vessels present in sponge isografts are consistently found in close proximity to nerve bundles. Although this MECA 325 reactive vessel-nerve bundle association is also observed in sponge allografts, large MECA 325 reactive vessels are widely distributed in allografts. Our data suggest that small, poorly adhesive MECA 325 reactive vessels develop in sponge isografts and allografts, possibly under the influence of local nerve tissue. These vessels respond to regional alloimmune responses by developing into the larger HEV-like vessels capable of binding lymphocytes in sponge allografts. The value of this experimental system as an in vivo model to evaluate mechanisms involved in neovascularization and endothelial differentiation is discussed.

Animals↗
PubMed2000

Immunogenicity and protective capacity of Mycobacterium bovis BCG after oral or intragastric administration in mice.

After oral or intragastric administration of BCG to mice, comparable numbers of IFN gamma and TNF gamma producing cells were detected in both local (Peyer's patches) and central (spleen) lymphoid organs. Similar levels of precursors of CD8+ cytotoxic T lymphocytes specific for mycobacterial antigens were also found in the spleen and the mesenteric lymph nodes. These immune responses remained high over the course of 3 months, the duration of observation. Oral administration of BCG led to an enlargement of the cervical lymph nodes, which contained high levels of viable bacteria. In contrast, no adverse effects were observed in mice given the BCG via the intragastric route. These two routes of immunization induced similar levels of protective immunity to those observed in mice immunized via the subcutaneous route against a challenge with a virulent Mycobacterium tuberculosis strain (H37Rv).

Administration, Oral↗
PubMed1988

Systemic uptake and intestinal inflammatory effects of luminal bacterial cell wall polymers in rats with acute colonic injury.

The systemic uptake and local intestinal inflammatory potential of luminal bacterial cell wall polymers in rats with normal and acutely inflamed colons were measured. Rats were injected intracecally with either 125I-labeled group A streptococcal peptidoglycan-polysaccharide complexes or equal amounts of Na125I, after either nonspecific colonic injury with 4% acetic acid or injection with buffer. The colons of rats injected with peptidoglycan-polysaccharide had higher inflammatory scores than Na125I-injected rats, a greater incidence of mucosal ulceration and transmural inflammation after acetic acid injury, and an increased frequency of focal accumulations of inflammatory cells in the lamina propria and submucosa after buffer injection. Radioactivity in the liver, spleen, and mesenteric lymph nodes was higher in the colon-injured rats that received peptidoglycan-polysaccharide 48 h before tissue collection than in the noninjured rats (P less than 0.002). Group A streptococcal polysaccharide antigen concentration within the liver, spleen, and mesenteric lymph nodes, measured by enzyme-linked immunosorbent assay, was significantly higher in the colon-injured rats that received cell wall polymers than in noninjured rats. These results indicate that luminal bacterial cell wall polymers with well-described inflammatory and immunoregulatory potential can cross injured colonic epithelia and are capable of initiating and potentiating intestinal inflammation.

Animals↗
PubMed2005

Primary antitumor immune response mediated by CD4+ T cells.

Gene-targeted mice have recently revealed a role for lymphocytes and interferon-gamma (IFNgamma) in conferring protection against cancer, but the mechanisms remain unclear. Here, we have characterized a successful primary antitumor immune response initiated by naive CD4+ T cells. Major histocompatibility complex class II (MHC-II)-negative myeloma cells injected subcutaneously into syngeneic mice were surrounded within 3 days by macrophages that captured tumor antigens. Within 6 days, naive myeloma-specific CD4+ T cells became activated in draining lymph nodes and subsequently migrated to the incipient tumor site. Upon recognition of tumor-derived antigenic peptides presented on MHC-II by macrophages, the myeloma-specific CD4+ T cells were reactivated and started to secrete cytokines. T cell-derived IFNgamma activated macrophages in close proximity to the tumor cells. Tumor cell growth was completely inhibited by such locally activated macrophages. These data indicate a mechanism for immunosurveillance of MHC-II-negative cancer cells by tumor-specific CD4+ T cells through collaboration with macrophages.

Animals↗
PubMed1978

Cytotoxic activities of gut mucosal lymphoid cells in guinea pigs.

Populations of lymphoid cells were obtained from the gastrointestinal tract of guinea pigs and compared with splenic cells for effector cell activity in assays of spontaneous cell-mediated cytotoxicity (SCMC), mitogen-induced cellular cytotoxicity (MICC), and antibody-dependent cellular cytotoxicity (ADCC). Lymphoid cells were isolated from mesenteric lymph nodes (MLN), Peyer's patches (PP), and the small intestinal mucosa. Mucosal lymphoid cells were separated into a population of cells containing intraepithelial lymphocytes (IEL), and a second population of cells containing intraepithelial lymphocytes (IEL), and a second population of cells containing lamina propria (LP) lymphocytes by a combination of physical and enzymatic methods. All populations of lymphoid cells from the gastrointestinal tract were capable of mediating MICC. Relative to spleen cells, IEL possessed more MICC effector cell activity whereas cells from MLN, PP, and LP possessed less activity. In contrast, SCMC and ADCC effector cell activities were present only in the IEL population and these cytotoxic activities were comparable to that of splenic cells. These results demonstrate that mucosal lymphoid cells possess cytotoxic effector cell activities that may contribute to local mucosal immunologic reactivity.

Animals↗
PubMed1991

Clinical significance of tumor marker NCC-ST 439 in large bowel cancers.

We examined serum NCC-ST 439 for its significance as a tumor marker of large bowel cancer in 121 patients with primary and 36 with recurrent large bowel cancer. Serum NCC-ST 439 was positive in 27.3 percent of the former and 66.7 percent of the latter. It was false-positive in only 5.6 percent of patients with benign diseases. Positive serum NCC-ST 439 correlated with lymph node and liver metastases. The combination assay for NCC-ST 439, CEA, and CA19-9 was positive in 49.6 percent of the patients with primary tumors and 88.9 percent of those with recurrent tumors; in other words, the diagnostic accuracy improved. The results demonstrated that the determination of serum NCC-ST 439 in large bowel cancer might be useful in cancer staging and that NCC-ST 439, if used in combination with CEA, is particularly useful in diagnosing recurrences because of its improved diagnostic accuracy.

Antibodies, Monoclonal↗
PubMed1986

Double immunocytochemical staining for the in situ study of allotype distribution during an anti-trinitrophenyl immune response in chimeric rabbits.

After incubation of tissue sections with anti-allotype-enzyme conjugates, the localization of immunoglobulin-allotype-bearing cells in the lymphoid tissues of conventional and chimeric rabbits could be established. The use of anti-allotype sera bearing distinct enzyme labels allowed simultaneous recognition of B cells producing immunoglobulin of one or the other parental types in heterozygous rabbits, or of B cells from the donor and recipient in chimeras. After immunization of chimeric rabbits with trinitrophenyl-keyhole limpet hemocyanin, anti-trinitrophenyl antibody-forming cells could be demonstrated through the use of a trinitrophenyl-alkaline phosphatase conjugate. Simultaneous incubation of sections with this reagent and with horseradish peroxidase coupled to (donor or recipient) anti-allotype sera made possible the determination of the origin (donor or recipient) of the antibody-forming cells. In agreement with the results of plaque assays and analyses of serum antibodies, all the anti-TNP producing cells were of donor origin when the chimeras had been created through injection of spleen or lymph node cells from trinitrophenyl primed donors. With this study we introduce a simple, direct method for the simultaneous identification of cells that produce antibody of a given allotype and a given specificity, applicable to appropriate studies in heterozygous or chimeric rabbits. The procedure has various advantages over previously reported methods.

Alkaline Phosphatase↗
PubMed1984

Interaction between genes of chromosome 12 and I-region genes in the control of the arsonate-specific T cell repertoire.

The T lymphocyte repertoire consists of clones recognizing foreign antigens together with self histocompatibility molecules. Diversification of the receptor is believed to arise by somatic mechanisms during ontogeny. MHC gene products are essential for this process as well as for antigen recognition and expression of T cell functions. Yet, the antigen-specific T cell receptor is not encoded by MHC genes. Little is still known concerning the nature and the genetic origin of this receptor despite numerous experimental approaches. Although the T cell repertoire is mainly determined, in a single individual, by the alleles expressed at the MHC locus, one can postulate that it could also be influenced by the existence of alleles of the germ line gene(s) encoding the T cell receptor. If so, an analysis of the T cell fine specificity in mice of the same H-2 haplotype with different background genes might permit the mapping of the genes coding for this receptor. Such an experimental approach requires the use of an antigen consisting of only one major determinant. Several recent observations suggested to us that the hapten p-azobenzenearsonate (ABA) was a suitable model for such investigations. Thus, we decided to compare the specific pattern of responses to ABA-tyrosine, ABA-histidine and to free ABA in different inbred mouse strains. We report here that the lymph node T cell proliferative response to these molecules is under the control of an ABA-specific Ir gene. The ABA-Tyr conjugate is the most potent immunogen of the three in vivo as well as in vitro. High responder strains to ABA-His or ABA are included in the group of high responders to ABA-Tyr suggesting that the response to the three molecules is under the control of the same Ir-gene. The pattern of the response is also influenced by background gene(s). One of these can be localized on chromosome 12 using congenic mice. No close linkage to IgCH markers or VH idiotypes can be demonstrated but a linkage of this gene(s) to the Pre-1 locus seems possible. B lymphocytes do not seem to account for the involvement of Chr.12-genes in the response since; in our experimental system, they do not present ABA to T cells nor do they proliferate in the assays. Similarly, ABA-Tyr-antibody complexes do not enhance macrophages presentation of ABA to T cells, which supports the conclusion that IgCH or VH gene products are not involved in the control of the response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2001

Technical aspects of minimal residual disease detection in carcinoma patients.

The burden of occult malignant cells which remains after a course of treatment that has resulted in clinical remission is referred to as minimal residual disease (MRD). MRD is increasingly considered as a determinant of local or systemic recurrence in cancer patients. During the last 20 years, methods for the detection of rare cancer cells have evolved from mere cytomorphological investigations to a variety of immunological and molecular assays. Since surgical therapy remains the best treatment option for cancer patients with resectable tumors, the first question to address is whether the removal of the tumor was complete or some cancer cells remained from the tumor at the primary site. Several tumor-associated DNA alterations have been identified to solve this diagnostic problem. Assays detecting tumor-associated DNA alterations have been applied to resection margins and body fluids such as bronchoalveolar lavage, sputum, urine, pancreatic juice, colonic lavage, and stool. Due to the higher sensitivity of immunocytochemical and reverse-transcriptase polymerase chain reaction (RT-PCR)-based assays, the second question to be addressed is whether systemic hematogenous or lymphatic spread of cancer cells occurred. Disseminated cancer cells have been detected in bone marrow aspirates, peripheral blood, and lymph node biopsies, and cancer cell dissemination is regarded as a relevant and independent prognostic factor. Thus, sensitive techniques for the detection of MRD are likely to guide indications for surgical or adjuvant therapy protocols in clinical oncology. However, since many of the assays for the detection of MRD are complex, and results are influenced by a variety of technical aspects, the majority of diagnostic applications have not yet been sufficiently standardized. Consequently, quality control and reproducibility of minimal disease detection assays remain unsolved problems. Therefore, well controlled collaborative studies are urgently required to evaluate indications and diagnostic standards for these assays. This review summarizes technical aspects and their implications for the clinical application of presently available assays for MRD detection in carcinoma patients.

Carcinoma↗