An overview: Antitumor immunity in breast cancer assayed by tube leukocyte adherence inhibition

Flores, María Elena; Marti, Jacques; Grosser, Nina; MacFarlane, John K.; Thomson, David M.

doi:10.1002/1097-0142(197702)39:2<494::aid-cncr2820390218>3.0.co;2-8

Cited by 50 publications

(23 citation statements)

References 27 publications

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“…Fig. 1 shows that the optimum tumourdirected LAI response (NAI value) is observed at 100 ,ug protein/tube, and as previously observed (Flores et al, 1977;Thomson, 1975, 1976; does not have a quantifiable dose-response.…”

Section: Resultssupporting

confidence: 79%

“…Holan et al (1974) described a modified LAI assay in a rat model that was performed in glass test tubes. In our laboratory, we successfully adapted and modified the glass test-tube assay (tube LAI assay) and it was shown to be a reliable, reproducible qualitative assay for the detection of tumour antigen or of specific antitumour immunity in patients suffering from either breast cancer or malignant melanoma (Flores et al, 1977;Grosser and Thomson, 1975;Grosser and Thomson, 1976;Marti, Grosser and Thomson, 1976;Thomson et al, 1976;Lopez and Thomson, 1977). Comparable results in these and other tumour systems have been found by other investigators (Powell et al, 1975;Rutherford et al, 1977;Leveson et al, 1977;Fujisawa, Waldman, and Yonemato, 1977).…”

mentioning

confidence: 72%

“…In the present study, when the isolated papain-soluble TSA and reactive leucocytes were from patients with cancers of similar origin and histology, the papainsoluble TSA was able to inhibit the glass adherence of the leucocytes to a greater extent than papain-soluble TSA or PBS tumour extracts from an unrelated tumour. However, the standard tube LAI assay performed in serum-free medium is highly dependent on protein concentration (Grosser and Thomson, 1975;Flores et al, 1977;Lopez and Thomson, 1977;Thomson, 1978) and titration of the isolated papain-soluble antigens below 50 ,ug becomes unreliable because the number of nonadherent cells is too few to be counted with any consistency. Hence, a blocking tube LAI assay Lopez and Thomson, 1977;Thomson, 1978) was used to quantitate the TSA activity in the isolates.…”

Section: Discussionmentioning

confidence: 99%

“…Tube leucocyte adherence inhibition assay (tube LAI assay) The tube LAI assay was performed and the results computed as previously described (Flores et al, 1977; Thomson, 1975; . Based upon studies of a large number of patients with breast cancer, malignant melanoma, and control subjects with unrelated neoplastic disease or non-cancerous diseases, a Nonadherence Index (NAI*) of 30 or more has been established as a positive LAI test with either PBS-extracted tumours or papainsolubilized tumour-antigen preparations (Flores et al, 1977; ; .…”

Section: Tumour Tissuesmentioning

confidence: 99%

“…Based upon studies of a large number of patients with breast cancer, malignant melanoma, and control subjects with unrelated neoplastic disease or non-cancerous diseases, a Nonadherence Index (NAI*) of 30 or more has been established as a positive LAI test with either PBS-extracted tumours or papainsolubilized tumour-antigen preparations (Flores et al, 1977; ; . The protein content of samples was measured by the procedure of Lowry et al (1951) with bovine serum albumin as a standard.…”

Section: Tumour Tissuesmentioning

confidence: 99%

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Isolation of human tumour-specific antigens associated with β2 microglobulin

Thomson¹,

Rauch²,

Friedlander³

et al. 1978

Br J Cancer

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Summary.-In the present study the tube LAI assay was used to monitor the isolation of the TSA of 4 different types of human cancers. Each tumour antigen was found to be specific for tumours arising in the organ from which the TSA was initially derived and which were histopathologically similar. Immunochemical studies revealed that these molecules co-isolate with normal human HLA antigens and are associated with fl2m. On Sephadex G-150, the majority of the papain-solubilized tumour antigen eluted in the mol. wt range 70,000-150,000. Analysis of this material by SDS-PAGE and 6M guanidine-HCl column chromatography indicated that the material is composed of smaller subunits with prominent peaks at 40,000, 25,000 and 12,000 mol. wt. Immunoadsorbent affinity chromatography of the solubilized tumour-membrane constituents on AH-Sepharose-linked horse anti-human-fl2m indicated that the tumour antigens, like HLA molecules, contain a /32m subunit. The specificity of binding of TSA to the immunoadsorbent columns and the immunologically specific abrogation of LAI reactivity were clearly shown. The present study, therefore, indicates that by the isolation of fl2m, human tumour antigens can also be Isolated, since human tumour antigens are associated with fl2m. Whether human TSAs may perhaps be modified histocompatibility antigens remains to be answered. Although the change upon malignant transformation in the pattern of the cell-surface proteins expressing the TSA determinant remains obscure, it would appear that for tumours arising within a given organ, a consistent alteration of cell-surface proteins occurs.

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Section: Resultssupporting

confidence: 79%

mentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Tumour Tissuesmentioning

confidence: 99%

Section: Tumour Tissuesmentioning

confidence: 99%

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Isolation of human tumour-specific antigens associated with β2 microglobulin

Thomson¹,

Rauch²,

Friedlander³

et al. 1978

Br J Cancer

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Isolation of HLA and tumor antigens by means of affinity chromatography employing anti-β2,-microglobulin (β2m) antiserum

Rauch¹,

Shuster²,

Thomson³

et al. 1978

Cancer

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A method for the isolation of HLA antigen molecules from normal and cancerous solid human tissue is described. The method employs anti‐β2‐microglobulin (β2m) antiserum coupled to Sepharose beads as an immunosorbent affinity medium. The anti‐β2m affinity chromatography procedure greatly purifies and selectively enriches HLA and any material that copurifies by affinity, with β2m and /or HLA molecules. The HLA isolated by this purification procedure was used to immunize rabbits. The antisera obtained were absorbed on β2m to remove all anti‐β2m antibody activity. The use of such anti‐HLA antisera in radioimmunoassays, immunoprecipitation studies, and F(ab′)2 blocking experiments demonstrated that these antisera are directed against a common HLA determinant present on the heavy (alloantigen‐bearing) chain of all HLA molecules. The use of an identical procedure employing human tumor tissues has resulted in the isolation of HLA‐like or HLA‐associated tumor‐specific antigens as demonstrated by the leukocyte adherence inhibition (LAI) assay.

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Tube leukocyte adherence inhibition (LAI) assay in gastrointestinal (GIT) cancer

Tataryn

MacFarlane

Murray

et al. 1979

Cancer

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Tumor-specific immunity to carcinoma of the colon, pancreas and stomach was assayed by tube LAI. Cancers of the colon, pancreas and stomach, were shown to possess organ-type specific neoantigens. In 115 patients with colon cancer, loo%, 75%, 61% with Dukes' A, B and C cancer were LA1 positive, respectively. Even a microfocus of in situ cancer in a colon adenoma was sufficient to stimulate measurable tumor-specific immunity in the host. In Dukes' D cancer, 25% of patients with widespread metastasis were positive, whereas 100% with solitary lesions were positive. Reactive leukocytes from patients with colon cancer did not react to extracts of normal bowel mucosa or villous adenoma from LAI-negative patients. Leukocytes from 19% (3 of 16) of patients with colon adenomas reacted to the extract of colon cancer but not normal colon mucosa. Moreover, the LAI-positive response of the patients with colon adenomas or colon cancer is directed to a colon cancer TSA which is linked to µglobulin. These studies suggest that some colon adenomas express TSA before morphological evidence of cancer. It is not known if the acquisition of a cell surface TSA is an irreversible step toward unrestrained growth and metastasis. In pancreatic cancer, 100% of patients with cancers less than 5 cm and without metastasis were LA1 positive, whereas 29% were positive when the cancer was >5 cm or had metastasized. In Patients with stomach cancer, 100% with Stage I1 and 46% with Stage I11 and IV cancer were LAI-positive. Leukocytes from patients with other GIT cancers and from patients with inflammatory bowel disease or pancreatitis did not react with extracts of colon, stomach or pancreatic cancer. Leukocytes, from patients with metastatic cancer, usually did not react in the tube LA1 assay because their surfaces were coated in vivo with TSA. LA1 reactivity was present when CEA was not detectable and when CEA levels were elevated LA1 activity was often absent. The present study suggests that the automated tube LA1 shows sufficient promise to warrant studies to determine its efficacy for the diagnosis of GIT cancers.Cancer 43:898-912, 1979.

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An overview: Antitumor immunity in breast cancer assayed by tube leukocyte adherence inhibition

Cited by 50 publications

References 27 publications

Isolation of human tumour-specific antigens associated with β2 microglobulin

Isolation of human tumour-specific antigens associated with β2 microglobulin

Isolation of HLA and tumor antigens by means of affinity chromatography employing anti-β2,-microglobulin (β2m) antiserum

Tube leukocyte adherence inhibition (LAI) assay in gastrointestinal (GIT) cancer

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