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Biomedical subjects

J K MacFarlane

Publications and source records attributed to J K MacFarlane.

At least 55 records · Page 3Linked to original sources
PubMed1981

Multi-drug chemotherapy with and without radiation for carcinoma of the stomach and pancreas: a prospective randomized trial.

A prospectively randomized trial in advanced gastric and pancreatic carcinoma compared multi-drug chemotherapy, with and without radiotherapy to the local lesion, in terms of median survival and toxicity. Of 29 patients with gastric adenocarcinoma, 14 were randomized to receive 5-FU and Methyl-CCNU, and 15 to receive 5-FU and local radiotherapy to a dose of 4600 rad, and then Methyl-CCNU. Thirty patients with advanced adenocarcinoma of the pancreas were similarly randomized. There was no significant difference between the two arms of the gastric or pancreatic adenocarcinoma groups, with a median survival of 13 months and 11.5 months respectively in gastric carcinoma, and 7.8 months and 7.3 months in pancreatic carcinoma. Complications were minimal in both groups. There was more hematopoietic depression in the radiation-treated patients, but none had radiotherapy discontinued because of toxicity.

Adenocarcinoma↗
PubMed1980

Studies on estrogen receptors and regression in human breast cancer.

Estradiol receptors were studied both qualitatively and quantitatively in 650 cases of breast cancer to obtain information on molecular forms and relationship with response to endocrine therapy. Cytosol estradiol receptor (ERC) was assayed by a charcoal method following incubations with 3H-estradiol and also by chromatography on Sephacryl columns. Results were classified as positive (10 fmoles/mg P and up), borderline (3-10 fmoles) and negative (0-3 fmoles). It was found that 44.6% of tumors were positive, 14.15% were borderline, and 41.2% were negative. Qualitatively, two major molecular forms of ERC were identified with molecular weights 31,000 and approximately 250,000. ERC level and response to endocrine therapy were correlated in a group of 52 patients. Response rate to hormonal therapy only was 59% in the ERC-positive, 28% in the borderline, and 9% in the ERC-negative group. Combination therapy, including endocrine manipulation, chemotherapy, and/or radiation improved response rates to 66% in the ERC-positive, 40% in the borderline, and 33% in the ERC-negative group. Defects in the translocation of the cytosol estradiol receptor (ERC)-estradiol complex to the nucleus could partly explain the failure of endocrine therapy in 40% of patients with significant ERC. To examine this possibility, 98 cases of breast cancer were examined for both ERC and nuclear translocation of estradiol (ERN). Nuclei were isolated from the low speed sediment and incubated with the ERC-3H-estradiol complex in the presence and absence of an estrogen competitor. After incubation, ERN was extracted from the nuclei and expressed as specifically bound estradiol, fmoles/mg DNA. Of 44 cases with significant ERC, nine had no ERN (20%). In the borderline group of 23 cases, eight had no ERN (34%), and of the 31 cases with zero or negligible ERC 27 had no ERN (87%). Results indicate that ERC-negative cases should be excluded from hormonal therapy and appear to benefit most from chemo- and/or radiation therapy. The absence of ERN in a significant proportion of ERC-positive cases probably contributes to the failure of hormonal manipulation in such patients. The results indicate that the determination of both ERC and ERN could improve the selection of patients for endocrine therapy.

Breast Neoplasms↗
PubMed1980

A computerized tube leukocyte adherence inhibition assay to detect antitumor immunity in early human cancer: a review of two years' experience.

A 2-year experience with a computerized in vitro assay of leukocyte adherence inhibition (LAI) indicated that patients with cancer of either the colorectum, stomach, pancreas, breast, or lung expressed antitumor immunity to an organ-type specific neoantigen. About 1% of the 1,299 control subjects with benign or malignant disease had a positive LAI assay and 2.5% of patients with inflammatory disease of the colorectum, stomach, pancreas, or lung had a positive LAI assay when tested against tumor extracts of the same organ. Of the 351 patients with cancer of either the colorectum (111), stomach (40), pancreas (28), lung (57), or breast (116) who harbored a microfocus of cancer, 80% or more were LAI positive. As the stage of the cancer advanced, fewer patients were LAI positive. Nine of 45 patients (20%) with colon adenomas had a positive LAI response to colon cancer antigen and 17 of 204 patients (8%) with benign breast disease reacted to the breast cancer antigen. Our results suggested that the leukocytes of some of the LAI-positive patients with either colon adenomas or benign breast disease were responding to an organ-specific neoantigen. Whether the acquisition of a cell surface tumor antigen by the colon adenomas and the dysplastic lesions of the breast implies an irretrievable step to ultimate malignancy is unknown. Most patients exhibit a vigorous antitumor immune response when the cancer exists as a microfocus, and some even before the neoplasm has acquired the capacity to invade.

Antigens, Neoplasm↗
PubMed1979

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

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, 100%, 75%, 61% with Dukes' A, B and C cancer were LAI 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 beta2-microglobulin. 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 LAI positive, whereas 29% were positive when the cancer was greater than 5 cm or had metastasized. In Patients with stomach cancer, 100% with Stage II and 46% with Stage III 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 LAI assay because their surfaces were coated in vivo with TSA. LAI reactivity was present when CEA was not detectable and when CEA levels were elevated LAI activity was often absent. The present study suggests that the automated tube LAI shows sufficient promise to warrant studies to determine its efficacy for the diagnosis of GIT cancers.

Adenoma↗
PubMed1978

Leucocyte adherence inhibition for detecting specific tumour immunity in early pancreatic cancer.

Tumour-specific immunity to pancreatic tumour antigens, assayed by an automated tube leucocyte-adherence inhibition assay (L.A.I.), was detected in 3 of 3 patients with localised pancreatic cancer and 3 of 8 patients with more extensive pancreatic cancer. Leucocytes from pancreatic cancer patients with L.A.I. reactivity did not react to antigens of stomach, colon, or lung tumours; leucocytes from patients with stomach, colon, or lung cancer of inflammatory disease of the pancreas and bowel did not show L.A.I. reactivity to pancreatic tumour antigens.

Adenoma, Islet Cell↗
PubMed1978

The natural history of antitumour immunity in human breast cancer assayed by tube leucocyte adherence inhibition.

The specificity of the tube LAI in breast cancer was examined in a study with coded samples of PBL. In addition, 64 patients with breast cancer had their LAI reactivity monitored and correlated with their clinical status for up to 3 years after mastectomy. When patients were assayed by tube LAI, 83, 72, and 29% with Stage I, and II and III breast cancer respectively were positive. In Stage IV brest cancer, 88% of those with local recurrence and 15% of those with disseminated cancer were positive. By contrast, 3% of control subjects were LAI+. A select group of patients admitted to hospital with suspicious breast lumps that histopathologically proved to be benign breast disease (BBD) had a higher incidence of LAI+ (12%), whereas of outpatients with BBD only 2% were LAI+. Most breast cancer patients LAI reactivity became negative 2--4 months after mastectomy, even when some harboured micrometastases. LAI reactivity remained absent in those patients who remained clinically "cancer-free". In the follow-up patients, LAI activity returned about 4 months before local recurrence. LAI reactivity was observed in 7/8 patients in the coded study and 14/15 patients in the follow-up study preceding and/or at the time of local recurrence. A few patients (15%) progressed to widespread cancer without preceding positive LAI activity. The results suggest that tumour-specific immunity rapidly fades after surgery and may play no role in the rejection of micrometastases by 6 months after surgery. In addition, the present study has shown that the human hose manifests tumour-specific immunity when the cancer is small, and suggests that the early detection of human cancer would depend upon reliable methods to measure the tumour-specific immune response.

Breast Neoplasms↗
PubMed1978

A study of false positive and negative responses in the tube leucocyte adherence inhibition (tube LAI) assay.

A panel of 5 different breast-cancer and 2 other cancer extracts was used to clarify the false-negative responses in patients with Stage I and II breast cancer and the false-positive responses in control subjects. Most patients with Stage I and II breast cancer who had an initially negative LAI response were positive when tested against the panel. The false negatives occurred because of (1) the experimental errors of the assay; (2) changes in the antigenic strength of the extracts; (3) antigenic heterogeneity of a few tumours and (4) lack of tumour-specific reactivity of the host. 3% of control subjects had a false-positive LAI response. The leucocytes from most of these positive patients did not react to the panel of antigens, and hence the false positives appeared to result from experimental error. In-hospital patients with benign breast disease had a 12% positivity rate when initially assayed, and 63% of these patients reacted to the panel of breast-cancer antigens. Those patients with benign breast disease who reacted to the panel of breast-cancer antigens had cytophilic anti-breast-cancer antibody in their serum; their leucocyte LAI reactivity was blocked in an immunologically specific manner by serum from advanced Stage IV breast-cancer patients; their leucocytes reacted to extracts of breast cancer and not fibrocystic breast tissue; their leucocyte reactivity was blocked by isolated breast-cancer TSA that was linked to beta 2 microglobulin, but not by normal breast-tissue proteins; and the kinetics of the LAI response after excision of the breast mass was identical to that observed with breast-cancer patients after mastectomy. In these patients, the breast tissue within the breast lump expressed breast TSA similar to unequivocal breast cancer.

Antigens, Neoplasm↗
PubMed1977

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

The adherence to glass of human peripheral blood leukocytes (PBL) incubated with tumor antigen in vitro, is specifically inhibited if the PBL are sensitized to the antigen. The presence of leukocyte adherence inhibition (LAI) to tumor extracts indicates the presence of systemic antitumor immunity. By the tube leukocyte adherence inhibition assay (tube LAI), it was shown that 85% (191 of 223) Stage I and II, 45% (15 of 34) Stage III and 29% (30 of 103) Stage IV breast cancer patients had LAI reactivity. LAI responsiveness diminished with an increased tumor burden and most patients with advanced cancer exhibited no LAI reactivity. When LAI reactivity was monitored for 1 to 6 months after surgery, 13 of 25 Stage I and II breast cancer patients were negative on the first repeat assay. In general, 7 months after mastectomy most patients clinically free of cancer showed no LAI reactivity. Of thirty-five patients tested between 7 and 18 months after mastectomy, 6 were positive and 4 of the positives had local recurrence. The phenomenon of tube LAI appears to be mediated by monocytes armed with cytophilic antitumor antibody. The serum of patients whose leukocytes responded in the tube LAI assay had free cytophilic antitumor antibody that "armed" or sensitized normal leukocytes to respond in the LAI assay. Serum arming paralleled leukocyte reactivity before and after surgery. Patients with advanced cancer whose leukocytes failed to react in the LAI assay had serum blocking factors (excess tumor antigen) that abrogated the LAI reactivity of leukocytes from reactive patients.

Antibodies, Neoplasm↗
PubMed1977

Cortisol in human breast cancer tissue.

Endogenous cortisol levels were measured by radioimmunoassay in 140 primary and 31 metastatic human breast cancer specimens. The adjacent normal breast was assayed in 15 cases. Mean values for normal breast were 17.3 ng/g tissue. Significantly higher levels were found in cancer tissue. Primary lesions contained 26 ng/g and metastases 32.5 ng/g cortisol. These results lend support to our previous data on increased cortisol binding activity in human breast cancer.

Breast Neoplasms↗
PubMed1977

Macromolecular binding of glucocorticoids in human mammary carcinoma.

The presence of glucocorticoid receptors was examined in 100 primary and 22 metastatic human breast cancer lesions. Aliquots of cytosol were incubated in vitro with tritiated cortisol and dexamethasone with and without competing steroids. Two different types of glucocorticoid receptors were detected. One is similar to transcortin; it sediments at 4 S in the ultracentrifuge, has a dissociation constant in the same range (10(-8) M), and does not bind fluorinated corticosteroids. While every tumor showed cortisol binding, very high activity (greater than 1000 fmoles/g tissue) was detected in 38% of primaries and in 59% of metastases. Plasma transcortin could be excluded as the source of binding activity. The other receptor binds both natural and fluorinated corticosteroids, has a higher affinity (Kd 10(-9) M), and sediments at 8 S. It was present in 23% of tumors and its quantity (26 to 995 fmoles/g) was much less than that of cortisol binder (50 to 6000 fmoles/g). While there was no correlation between the two glucocorticoid receptors, 80% of dexamethasone receptor-positive cases also had estrogen receptor. The results indicate that a significant proportion of these tumors could be subject to glucocorticoid influence.

Adrenal Cortex Hormones↗