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Biomedical subjects

J J Tjandra

Publications and source records attributed to J J Tjandra.

At least 73 records · Page 4Linked to original sources
PubMed1990

Development of human anti-murine antibody (HAMA) response in patients.

Human anti-mouse antibody (HAMA) response was determined in the serum of 67 patients who received subcutaneously administered radiolabelled murine monoclonal antibodies (MoAb) (50 micrograms-3 mg) for immunolymphoscintigraphy and of 10 patients with advanced colorectal cancer who received murine MoAb-N-acetyl melphalan (MoAb-N-AcMEL) conjugates (amount of MoAb ranged from 120 mg/m2 body surface area to 1000 mg/m2 body surface area) as therapy. A pre-existing low level of apparent human anti-mouse antibody reactivity could be detected in the serum of normal subjects and patients prior to administration of murine MoAb. Subcutaneous administration of low doses of murine MoAb, as used in immunolymphoscintigraphy, was associated with a low incidence (4/67 or 6%) of elevated HAMA response; the use of F(ab')2 fragments was associated with the development of elevated HAMA response in one of three patients. By contrast, therapy with hepatic artery infusion of murine MoAb-N-AcMEL conjugates in three repetitive daily doses (each infusion lasting 2 h) elicited elevated HAMA responses in 10/10 (100%) patients, usually 1-3 weeks after the start of therapy. The HAMA response of patients in the therapy group was higher than those in the immunolymphoscintigraphy study and the use of steroids did not prevent the development of the HAMA response. Further administration of MoAb-N-AcMEL conjugates to a patient, who had already developed HAMA, led to 'serum sickness'-type symptoms and a transient reduction in the HAMA titres. The elevated HAMA response was polyclonal, containing increased levels of both immunoglobulin M and G (IgM and IgG) and was directed against mouse-specific determinant, the isotype (presumed to be the Fc portion), the F(ab')2 and the 'idiotype' of mouse immunoglobulins.

Animals↗
PubMed1990

Sessile adenomas of the rectum: a personal series 1974-1984.

Sessile (villous) tumours of the rectum are uncommon and individual surgeons are unlikely to have wide experience in their management. A study was made of a unique personal series (AMC) of 104 cases encountered from 1974 to 1984; minimum duration of follow-up was 5 years. Clinically obvious rectal cancers were excluded from the study. Ages ranged from 42 to 89 years (mean 64.9 years) with a male:female ratio of 1.5:1. The commonest clinical presentations of sessile tumours of the rectum were rectal bleeding (45%) and altered bowel habit (38%). Hypokalaemia was a very uncommon presenting symptom (1%). These tumours ranged in longitudinal diameter from 1 to 9 cm, with 66% of cases greater than 3 cm and 33% of cases greater than 5 cm. The incidence of malignancy in sessile adenomas greater than 3 cm (27%) was more than triple that of adenomas less than 3 cm (8%) and the presence of induration on rectal examination was the most reliable clinical indicator of the presence of malignancy. Local transanal diathermy excision was a satisfactory form of treatment for most sessile tumours of the rectum (benign and malignant); especially if they were less than 3 cm (0% recurrence rate). It had the added advantage of preserving the anal sphincter and was possible in a higher proportion of sessile tumours in the lower half of the rectum (89%) than those in the upper half of the rectum (42%). The overall recurrence rate after local transanal excision was 8% for benign sessile adenomas and 33% for those containing invasive carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1990

Colonic and breast carcinomas--association or metastases? Report of a case.

There is an increased incidence of colonic carcinoma in patients with breast carcinoma but colonic involvement secondary to breast carcinoma can also occur. The differentiation of the organ or origin (breast vs colon) of the abdominal tumour can be difficult and may benefit from the use of immunohistochemical staining with monoclonal antibodies that react preferentially with colon cancer (JGT) and breast cancer (3E1.2, BC2,BC3). Measurement of Mammary Serum Antigen (MSA) level as detected by the anti-breast monoclonal antibody (3E1.2) was also useful in the classification of tumours of uncertain origin.

Breast Neoplasms↗
PubMed1989

Reactivity of anti-human milk fat globule antibodies with synthetic peptides.

The nucleotide sequence of partial cDNA clones coding for the core protein of a human polymorphic epithelial mucin has recently been obtained, this mucin consists of a highly conserved 60 bp tandem repeat and the amino acids commonly found are PDTRPAPGSTAPPAHGVTSA. We synthesized three peptides, 1) P1.24 containing the 20 amino acids and four amino acids (PDTR) of the adjoining repeat; 2) P1.15 consisting of the first fifteen (PDTRPAPGSTAPPAH) and P1.09 the second nine amino acids (GVTSAPDTR) of peptide P1.24. The reactivities of the synthetic peptides with mAb known to react with breast cancer (BC1, BC2, BC3, HMFG-1, 3E1.2, and RCC-1) were studied. The synthetic peptide, P1.24, corresponding to the antigenic sequence predicted from the tandem repeat reacted with antibodies BC1, BC2, and BC3 (known to react with human milk mucin and mucin expressed in breast cancer) and the antibody HMFG-1 which was used to select the cDNA clones. In addition, the epitopes recognized by BC1, BC2, and BC3 appear to be in the same region of the molecule represented by their reactions with the nine amino acids in peptide P1.09 (GVTSAPDTR). By contrast, other antibodies such as 3E1.2 which reacts only weakly with components of human milk, and RCC-1 that detects a low Mr component (95 kDa) in breast cancer, had no specific reaction with the synthetic peptides, indicating that their epitopes are distinct from those of BC1, BC2, BC3, and HMFG-1. Inasmuch as the antibodies HMFG-1, BC1, BC2, and BC3 react with the fully processed milk mucin, it is likely that some of the peptide is exposed, even in the fully glycosylated molecule. Identification of the different epitopes could lead to the development of "second generation" mAb with enhanced specificity for breast carcinoma using the appropriate synthetic peptides as immunogens.

Amino Acid Sequence↗
PubMed1989

Immunolymphoscintigraphy for the detection of lymph node metastases from breast cancer.

The presence of metastases in the regional lymph nodes is the major prognostic factor in breast cancer in the absence of overt distant metastases and is also an important indicator of the need for adjuvant therapy in "early" breast cancer. Currently, the accurate assessment of axillary lymph node status requires axillary dissection which has an associated morbidity. An alternative method of identifying patients who are "node positive" has been developed by means of immunolymphoscintigraphy with s.c. administered radioiodinated monoclonal antibody. The 131I-labeled anti-breast cancer antibody (RCC-1; 400 micrograms) and cold iodine-labeled "blocking" antibody (Ly-2.1; 2 mg which is nonreactive with breast cancer) were injected s.c. into both arms and scintigraphy images were obtained 16-18 h after the injection, using the axilla contralateral to the side of the breast cancer as the control. Studies were reported as positive (and therefore indicative of lymph node metastases) if the amount of background-subtracted radioactive count in the axilla of interest exceeded the normal side by a radio equal to or greater than 1.5:1.0 as assessed by computer analysis. In 38 of 40 patients the findings on scintigraphy were correlated with operative and histopathological findings on the axillary dissection specimen or cytological findings of fine needle aspiration of axillary lymph nodes. In a prospective study of 26 patients, the method is more sensitive (86%) and specific (92%) than preoperative clinical assessment (57% sensitivity, 58% specificity) in the detection of axillary lymph node metastases; and by combining both modalities of assessment, there was an improvement in the sensitivity (100%) but a deterioration in the specificity (50%). There was no significant complication from this essentially outpatient procedure and only 1 of 40 patients developed a human anti-mouse antibody response. This novel and safe method of imaging may become a most useful adjunct in the surgical management of breast cancer.

Animals↗
PubMed1989

Purification and biochemical characterisation of a novel breast carcinoma associated mucin-like glycoprotein defined by antibody 3E1.2.

A member of the high molecular weight glycoproteins of human milk and breast cancer was isolated from the sera, ascites and breast carcinoma tissue of patients with breast cancer using monoclonal antibody 3E1.2. The 3E1.2 defined antigen, termed mammary serum antigen (MSA) was obtained by immunoaffinity chromatography and a solid phase immuno-precipitation technique (SPIT) from serum of patients with metastatic breast cancer. MSA was found to be a high molecular weight glycoprotein with a Mr greater than 300,000 by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and a native Mr approximately 1 x 10(6) by gel filtration chromatography; in accord with the published Mr of other high molecular weight glycoproteins obtained from human milk and breast cancer. A high degree of glycosylation of MSA molecule was shown by its poor staining with Coomassie blue but good staining in a PAS-silver stain. In addition, MSA contained N-acetyl neuraminic acid and N-acetyl glucosamine as indicated by its binding to wheat-germ agglutinin. The epitope defined by antibody 3E1.2 is sensitive to treatment by sodium periodate and neuraminidase, implying that both carbohydrate and sialic acid are required for binding of antibody 3E1.2. Sandwich immunoassays demonstrated that MSA+ molecules are likely to express repeated 3E1.2 defined epitopes. Furthermore, MSA was susceptible to degradation by pronase, subtilisin and proteinase K and gave a different peptide profile from that of the PAS-O glycoprotein of human milk. MSA+ molecules were found to carry epitopes for a number of other monoclonal antibodies which were reactive with the PAS-O glycoprotein. It is suggested that MSA has the same core protein as is recognised by antibody DF3 which has been used to clone the same cDNA as was cloned with antibodies HMFG-1, HMFG-2 and SM-3. However, the epitope detected by the 3E1.2 antibody is either absent or weakly expressed on human milk, human milk-fat globule membrane (HMFGM) or deglycosylated HMFGM--all of which react strongly with various anti-HMFG antibodies. The antibody 3E1.2 thus recognises a unique epitope of the high molecular weight glycoproteins of human milk and breast cancer, being found in cancer tissue, serum and ascitic fluid of patients with breast cancer but weakly expressed or absent in human milk.

Antibodies, Monoclonal↗
PubMed1989

The detection of axillary lymph node metastases from breast cancer by radiolabelled monoclonal antibodies: a prospective study.

In a prospective study to assess the accuracy of monoclonal immunoscintigraphy for the detection of axillary lymph node metastases in breast cancer, two murine monoclonal antibodies that react with human breast cancer (3E1.2 and RCC-1) were labelled with 131iodine, and the radiolabelled antibody was injected subcutaneously into the interdigital spaces of both hands of 40 patients, 36 of whom had breast cancer and the remaining four of whom had fibroadenoma (the normal, contralateral axilla was used as a control). Of the patients with breast cancer, the findings from the scintigraphy images were correlated with histopathology or cytology of the axillary lymph nodes; images were regarded as positive and hence indicative of lymph node metastases if the amount of background-subtracted radioactive count in axilla on the side of breast cancer exceeded the contralateral normal side by a ratio greater than or equal to 1.5:1.0 as assessed by computer analysis. Using this method, immunoscintigraphy had an overall sensitivity of 33% (23% with 131I-3E1.2 and 50% with 131I-RCC-1) for the detection of lymph node metastases and a specificity of 63% (67% with 131I-3E1.2 and 60% with 131I-RCC-1) with problems of non-specific uptake by presumably normal lymph nodes. The results of immunoscintigraphy obtained with 131I-RCC-1 (IgG) were superior to 131I-3E1.2 (IgM) although the accuracy of immunoscintigraphy using 131I-RCC-1 (56%) was not much better than preoperative clinical assessment (50%). However, there were cases when immunoscintigraphy using radiolabelled antibody (IgM or IgG) detected axillary lymph node metastases not suspected by clinical examination. Thus it appears that while immunoscintigraphy may be a useful adjunct to preoperative clinical assessment and is simple and safe, a major improvement in its accuracy is needed before it can replace axillary dissection and histological examination in the accurate staging of axilla in breast cancer.

Antibodies, Monoclonal↗
PubMed1989

Monoclonal antibodies reactive with mucin expressed in breast cancer.

Three murine monoclonal antibodies (BC1, BC2 and BC3) were developed against human milk fat globule membrane (HMFGM). By immunoperoxidase staining, it was found that the antigenic determinants had a predominant distribution in breast cancer tissue. In addition, the antibodies reacted preferentially with mucin derived from human milk rather than that derived from the breast cancer cell line ZR75; they also recognized polymorphic high molecular weight components (MW greater than or equal to 230,000) in serum and in human milk fat globule membrane. Thus the antibodies appear to react with a component of the family of mucins found in breast cancer and human milk and it appears likely that at least part of each epitope is protein in nature. Antibodies BC1, BC2 and BC3 recognized related but not identical epitopes, and they appear to be co-expressed on the same molecules as 3E1.2-defined antigen (mammary serum antigen, MSA) which is also a member of the family of breast cancer-related mucin. However, the 3E1.2 epitope is distinct and non-cross-reactive with those described for BC1, BC2 and BC3. The BC2 and BC3 defined epitopes were examined for their value in serum assays. Immunoassay was developed with a combination of two antibodies, using antibody BC3 for antigen capture and antibody BC2 or 3E1.2 for antigen detection and gave reasonable sensitivity (approximately 85%) and specificity (approximately 95%) in such serum tests for breast cancer. In a limited study, these tests appeared to complement the MSA test in the detection of breast cancer.

Antibodies, Monoclonal↗
PubMed1989

Spinal arachnoiditis following subarachnoid haemorrhage.

Two cases of chronic adhesive spinal arachnoiditis following documented subarachnoid haemorrhage (SAH) are reported. Both cases progressed to severe spinal cord dysfunction with paraplegia. It is hoped that this case report will highlight this uncommon but extremely disabling complication of SAH.

Adult↗
PubMed1989

Phase I clinical trial of drug-monoclonal antibody conjugates in patients with advanced colorectal carcinoma: a preliminary report.

Melphalan (MEL), an alkylating agent, has been modified to a derivative, N-acetylmelphalan (N-AcMEL), which can be conjugated to anticolon cancer monoclonal antibodies (MoAbs 30.6, I-1, and JGT) and used for immunochemotherapy. The final immunoconjugates possess potent cytotoxicity and specificity in preclinical studies. In a phase I clinical study, N-AcMEL-MoAb conjugates were administered via the hepatic artery to 10 patients, nine of whom had disseminated colorectal cancer (including the liver) and one of whom had Dukes' C colon cancer that had been resected. The selection of MoAb was based on the immunoperoxidase staining of the primary colon cancer tissue. Thus far doses of 1000 mg/m2 MoAb conjugated to 20 mg/m2 of N-AcMEL have been administered with no significant side effects, whereas MEL unconjugated to monoclonal antibodies would have caused myelosuppression in a proportion of patients at the same dosage. Serum antimouse antibody responses were noted in all of the patients; febrile reactions were noted with higher doses but were easily controlled with antipyretics, antihistamines and, if necessary, steroids. Serum sickness developed in one patient who was given a second course of treatment in the presence of human antimouse antibody, but the episode was self-limiting. Eight of the 10 patients had evaluable disease. Subjective improvement was noted in almost all of the patients examined, and 33%, or 3 of 9, of the treatments (nine courses of treatment in eight patients with evaluable disease; one of the patients had two courses of treatment) led to antitumor responses (minor response) by objective assessment with computed tomography of the liver. It is important to note that treatment with N-AcMEL-MoAb conjugates was safe at a dose of 20 mg/m2 of N-AcMEL, whereas the efficacy of such a form of treatment remains to be determined.

Adult↗
PubMed1988

Comparison of mammary serum antigen assay with mammography in patients with breast cancer.

Mammary serum antigen levels and two-view xeromammography were evaluated in a study of 97 patients who presented at a specialist breast clinic in a major teaching hospital, in order to determine their single and combined value in the detection of breast cancer. Raised mammary serum antigen levels (greater than 300 inhibition units) were found in 76% of patients with stage-1 (including carcinoma-in-situ) and stage-II breast cancer compared with 54% of patients whose mammograms were suggestive of cancer (probability of carcinoma, greater than 50%). Four patients with carcinoma-in-situ had elevated mammary serum antigen levels, but their mammograms did not suggest the presence of cancer (probability of carcinoma, less than 50%). The over-all sensitivity, specificity and predictive value of a positive test-result in detecting breast cancer were 76%, 82% and 72%, respectively, for the mammary serum antigen test, and 54%, 88% and 74%, respectively, for mammography. When the mammary serum antigen test and mammography were used together, a combined evaluation enhanced the sensitivity in the detection of breast cancer (89%) but with a concomitant reduction in specificity (72%). The mammary serum antigen test was superior to mammography in the detection of breast cancer in this study and may prove to be a useful adjunct to conventional methods of clinical assessment and to mammography for the detection of breast cancer.

Adult↗
PubMed1988

Application of mammary serum antigen assay in the management of breast cancer: a preliminary report.

A monoclonal antibody (3E1.2) based serum test using an enzyme immunoassay has been used to determine circulating levels of the breast cancer associated antigen--mammary serum antigen (MSA). Of 157 patients with early breast cancer (stage I and II) and 199 patients with advanced breast cancer (stage III and IV), 73 per cent and 87 per cent respectively had elevated MSA levels (i.e. greater than 300 inhibition units (IU). Furthermore, 40 of 44 patients (91 per cent) had a significant fall of MSA levels with reduction in tumour load by mastectomy. In addition, there was a correlation of MSA levels with the clinical course: changes in MSA levels correlated with changes in disease status (progressive disease, stable disease, disease regression) in 54 of 61 patients and antedated disease progression or recurrence by up to 8 months in some patients; and in 32 of 36 patients (89 per cent) with no clinical evidence of recurrence MSA levels did not vary by more than 25 per cent of the original MSA value over a period of 2-15 months. MSA is therefore a useful tumour marker in the diagnosis and staging of breast cancer. There is also evidence that serial estimations of MSA levels may be used to detect subclinical recurrence and the fluctuations in MSA levels might be useful in assessing response to therapy. Furthermore, it was also noted that surgical procedures such as fine needle aspiration biopsy or incisional biopsy could lead to a rise in MSA levels.

Adult↗
PubMed1988

Murine monoclonal antibodies in breast cancer: an overview.

Monoclonal antibody technology has been an important development in breast cancer research. Monoclonal antibodies do not detect 'breast cancer specific' antigens but, rather, they react with normal or modified tissue antigens which are either preferentially or inappropriately expressed upon malignant cells. Thus far a number of monoclonal antibodies that have a preferential reaction with breast cancer tissue have been developed. They have a potential value in immunohistopathology as diagnostic tools and in the recognition of small quantities of malignant cells, in the development of serum assay for tumour markers in breast cancer and in the radio-immunodetection of metastases. There has been success in effecting selective targeting of anticancer agents (cytotoxic drugs, toxins, radionuclides) to tumour deposits and encouraging results are obtained in preclinical in vivo studies. Various clinical studies are now in progress to evaluate the role of monoclonal antibodies in the management of breast cancer.

Antibodies, Monoclonal↗
PubMed1988

Comparison of mammary serum antigen (MSA) with beta 2-microglobulin (beta 2M) and carcinoembryonic antigen (CEA) assays in patients with breast cancer.

Serum levels of mammary serum antigen (MSA), beta 2-microglobulin (beta 2M) and carcinoembryonic antigen (CEA) were evaluated in 186 subjects to assess their use in the diagnosis and monitoring of breast cancer, either singly or in combination. Raised MSA levels (greater than 300 I.U.) were detected in 79% of patients with Stage I/II breast cancer, compared with 25% for beta 2M (greater than 2000 micrograms/l) and 12% for CEA (greater than 5 ng/ml) levels respectively. Of 53 patients with Stage III/IV breast cancer, 98% (MSA), 55% (beta 2M) and 64% (CEA) had raised levels. In 25 patients followed over 3-9 months, the changes in MSA levels correlated with the clinical course of the disease in 23/25 (92%), compared with 7/25 (28%) using beta 2M, and 9/25 (36%) using CEA assays. The overall sensitivity, specificity and accuracy in detecting breast cancer were 88%, 95% and 99% for MSA; 39%, 90% and 96% for beta 2M; and 38%, 95% and 98% for CEA, respectively. MSA and beta 2M assays in combination enhanced the sensitivity in the detection of breast cancer (93%) especially early breast cancer, while maintaining specificity (90%). MSA seems to be superior to beta 2M or CEA as a tumour marker in breast cancer and its levels seem to correlate with tumour burden. While it appears that beta 2M or CEA measurements used alone are of little value in the current management of breast cancer, beta 2M may be a helpful adjunct to enhance the sensitivity of MSA assay especially in early breast cancer.

Antigens, Neoplasm↗
PubMed1988

Evaluation of MSA as a serum marker in breast cancer: a comparison with CEA.

In a blind study, 518 serum samples were assayed for serum levels of mammary serum antigen (MSA) by an enzyme immunoassay (EIA) using the 3E1.2 monoclonal antibody. Using 300 IU as the arbitrary cut off to distinguish normal from abnormal individuals, 75% of patients with primary Stage I carcinoma of the breast (n = 12), 89% of those with Stage II (n = 9) and 93% of those with Stage IV (n = 57) had elevated levels of MSA. A relationship was observed between the level of MSA and stage of disease, and therefore with the extent of tumour burden. Levels of MSA were also determined in a series of 19 patients undergoing chemotherapy for breast cancer. Over a 2-24 month period, the change of MSA levels corresponded with the clinical course of the disease in 17 (89%) cases. MSA levels were also raised in some patients with ovarian, colon, lung and kidney cancer, but the average level was lower than in patients with breast cancer. A comparison of CEA and MSA levels in these patients revealed that MSA was a substantially better marker for breast cancer than CEA. The results of this study demonstrate that MSA levels are elevated in patients with breast cancer and may provide a useful means of following the clinical course of patients with this disease.

Antigens, Neoplasm↗
PubMed1988

HLA (class I) antigens on platelets are involved in platelet function.

HLA (Class I) antigens are ubiquitous in their cellular distribution and, while their function in major histocompatibility complex (MHC)-restricted phenomena are clear, their function on other cells, such as platelets, is not so obvious. We now report that several anti-HLA monoclonal antibodies (including an anti-beta 2 microglobulin antibody) selectively affect platelet function in that three different anti-HLA monoclonal antibodies caused not only the aggregation of human platelets, but also caused the release of 14C-serotonin. In addition, the anti-HLA antibodies could selectively block the binding of several platelet agonists such as collagen, adrenalin, ADP, but not the binding of others such as thrombin and arachidonic acid. In blocking studies there also appeared to be an association between platelet glycoprotein IIb-IIIa and HLA Class I antigens. We propose that both heavy and light chains of Class I HLA antigens on platelets may be involved in platelet aggregation and release and suggest an additional role for HLA antigens on platelets.

Antibodies, Monoclonal↗