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Biomedical subjects

G Steele

Publications and source records attributed to G Steele.

At least 145 records · Page 8Linked to original sources

Immunogenicity and cross-protection among B16 melanoma variants with differing proclivities to metastasize.

We report here the lack of any relationship between immunogenicity and the potential to metastasize among four B16 melanoma variants. Groups of C57BL/6J mice were immunized with one of four B16 variant lines (maintained by serial IM passage) that were shown in separate experiments to produce the following incidences of pulmonary metastases four to six weeks after isograft excision: M1, 10%-15%; M2 10%-20%; M3, 75%-80%; and M4, 75%-90%. After immunization, mice were challenged with one of the four variant lines in a crisscross fashion. Two challenge doses for each line were chosen on the basis of earlier experiments showing 100% and 50% challenge tumor take in nonimmunized animals. Despite earlier work published from this laboratory showing that splenocytes harvested from immunized mice could distinguish antigenic differences among the B16 variants, we could find no significant difference in immunogenicity or cross-protection among the lines regardless of their metastatic potential. We conclude that no correlation exists between the antigenic differences shown by in vitro splenocyte-mediated cytotoxicity assays among the B16 variants and in vivo immunogenicity or cross-protection experiments. Futhermore, the relationship (if any) between immunogenicity and the ability to metastasize among these B16 variants is not straightforward.

Animals↗

Correlation of Plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer.

A review of patients operated on for colorectal cancer disclosed poorly differentiated histologies in those whose preoperative and postoperative carcinoembryonic antigen (CEA) levels were no elevated, even in the presence of metastatic disease. CEA was therefore, of little prognostic value or predictive of disease recurrence in these patients. The amount of CEA in tumor tissue of 17 patients with poorly differentiated colorectal cancer was estimated with the immunoperoxidase staining technique and was correlated with histology and plasma CEA levels obtained during various stages of disease. Five tumors did not stain negatively for CEA and all had predominantly poorly differentiated histologies. In all of these patients metastatic disease developed but not elevated plasma CEA levels. In contrast 12 tumors stained positively for CEA and were found to contain either differentiated areas or signet ring cells. Serial plasma CEA levels correctly monitored the postoperative course of all 12 patients. Six of these had a relapse and all were detected by serial increases in plasma CEA. The remaining six were disease free greater than 48 months after resection and had normal plasma CEA levels. Among poorly differentiated tumors, those that contain glandforming areas or signet ring cells can be assumed to produce CEA and plasma CEA levels can be used effectively for monitoring. On the other hand, undifferentiated tumors which do not stain for CEA identify those patients whose plasma CEA levels do not provide a useful monitor.

Adenocarcinoma↗

Application of polyethylene glycol turbidity assay to detection of circulating immune complexes in cancer patients.

A rapid, reproducible immune complex screening assay was used to quantitate levels of circulating immune complexes in the sera of normal subjects, patients with documented increases in immune complexes from rheumatoid arthritis, patients with clinically or microbiologically documented infections, and patients with cancer. Although wide variations in individual values within the groups were noted and the concurrent elevation of polyethylene glycol-circulating immune complex levels by infection was documented as expected, significant differences were found in the values in patients with cancer compared with those in normal subjects. The overall clinical application of polyethylene glycol-circulating immune complex screening is discussed and current application of screening of serial sera samples from individual patients for correlation with measurable tumor volume is proposed.

Antibodies, Neoplasm↗

Morbidity and mortality after surgery in patients with disseminated or locally advanced cancer receiving systemic chemotherapy.

All postoperative complications and mortality were analyzed in a diverse group of patients operated upon by the authors during a ten-year period. These patients shared only two common factors: 1) known locally advanced or disseminated cancer, and 2) systemic chemotherapy within three weeks (either pre- or postoperatively) of major surgery. One hundred eighty-six operations were performed on 175 patients. The overall mortality in this series was 2.2% (four patients), with a complication rate of 5.9% (11 patients). Despite the known detrimental effects of widespread cancer and cytotoxic agents on wound healing, appropriate surgical intervention can be accomplished with an acceptable mortality and morbidity in patients with locally advanced or disseminated cancer who are receiving systemic chemotherapy.

Adolescent↗

The use of preoperative plasma CEA levels for the Stratification of patients after curative resection of colorectal cancers.

One hundred forty-five patients with colorectal cancer were analyzed in order to correlate the preoperative plasma carcinoembryonic antigen (CEA) levels with the sites and times of disease recurrence. The median follow-up periods of these patients was 50 months (range 36-72 months). Twenty-one patients were found to have metastases at the time of their operation. None of the seven patients whose primary tumors were classified as Dukes/Kirklin A have had tumor recurrence. Seventeen per cent of the patients with Dukes/Kirklin B tumors have had tumor recurrences, and 63% of the patients with Dukes/Kirklin C colorectal primary tumors have had tumor recurrence. No correlation was found between preoperative CEA values and subsequent risk of tumor recurrence or times to recurrence among the patients with Dukes/Kirklin B colorectal primary cancers. In Dukes/Kirklin C patients, however, elevated preoperative CEA values predicted a higher risk of tumor recurrence. Ninety per cent of the patients (19/21) with preoperative CEA levels greater than 5.0 ng/ml have had relapses, with a median time of 17 months before disease recurrence. Only 39% (9/23) of the patients with Dukes/Kirklin C lesions and CEA levels less than 5 ng/ml have had relapses and there is insufficient follow-up data as yet to determine the median survival time. If those patients whose Dukes/Kirklin C primary tumors were poorly differentiated on histologic examination are excluded, the contrast between patients having CEA levels greater than 5.0 ng/ml and those having CEA levels less than 5 ng/ml is even more marked. Sixteen of the 18 remaining patients whose CEA levels were greater than 5.0 ng/ml prior to curative resection have had relapses as compared with only three of 15 patients whose preoperative CEA values were less than 5. We conclude, therefore, that CEA is an important factor in stratifying patients after curative resection of their Dukes/Kirklin C colorectal tumors.

Carcinoembryonic Antigen↗

Malignant intestinal obstruction.

The records of 66 consecutive patients who developed intestinal obstructions after treatment for cancer were reviewed. Approximately one third of the patients were found to have a benign cause of obstruction. The chances that an obstruction was due to cancer were increased if the patient had known metastatic cancer, previous colorectal cancer, if the primary was an advanced stage, and if the interval since treatment of the primary was short. Incomplete obstructions were treated with nasogastric suction. Although resolution of the obstruction on nasogastric suction without operation occurred in 24% of the admissions, 41% of those patients had to be readmitted for surgical relief of recurrent intestinal obstruction. Resolution of an obstruction on nasogastric suction occurred early, and there was little point in continuing a trial of suction for longer than 3 days.

Adolescent↗

Relationship of intestinal obstruction to serial plasma carcinoembryonic antigen levels.

Since it has been suggested that colonic obstruction due to carcinoma may play a role in elevations of circulating carcinoembryonic antigen, serial plasma carcinoembryonic antigen levels were studies in 19 patients with intestinal obstruction due to tumor and nontumor causes. Regardless of cause, eight of ten patients with colonic obstruction did not show decreased carcinoembryonic antigen levels after decompression. Two patients with postoperative carcinoembryonic antigen reductions of greater than 40 per cent had ascite removed at operation. Removal of a large volume of carcinoembryonic antigen-rich ascites was thought to contribute to the fall in circulating carcinoembryonic antigen. Six patients with small intestinal obstruction and one patient with large and small intestinal obstruction did not show a reduction in postdecompression carcinoembryonic antigen levels. One patient with Crohn's disease who underwent ileal resection and one with intestinal obstruction due to carcinoma of the ovary who underwent resection at the time of decompression had a greater than 40 per cent reduction in postoperative carcinoembryonic antigen levels. Inflamed intestinal and carcinoma of the ovary are known sources of carcinoembryonic antigen and their removal could explain the decrease in carcinoembryonic antigen. Rehydration, as monitored by plasma osmolality and protein concentration, did not explain changes in plasma carcinoembryonic antigen. Thus, it appears that carcinoembryonic antigen production may play a more significant role in the regulation of circulating carcinoembryonic antigen than the physiopathologic processes associated with obstruction.

Aged↗

Immunotherapy with RNA in cancer.

The effect of I-RNA therapy was studied in a B16 melanoma-C57BL/6J mouse system. After having primary B16 isografts excised, mice receiving syngeneic lymphocytes incubated in vitro with specific guinea pig B16 I-RNA showed significantly improved survival as compared to control mice receiving untreated lymphocytes. This therapeutic effect was tumor specific and RNase sensitive. Significant cytotoxicity against B16 cells in vitro was consistently observed with lymphocytes prepared from B16 I-RNA treated animals, whereas lymphocytes from control animals or those treated with RNase-degraded B16 I-RNA or 3LL I-RNA had no effect. Results suggest that the combination of surgery and immunotherapy with I-RNA may be useful in preventing tumor recurrence in certain patients with cancer.

Animals↗

Length of residence, life change and psychiatric morbidity in an Australian urban population.

A component of a large population study of a random sample of 750 Canberra residents is described, in which length of residence in Canberra is related to the quality and quantity of recent life experiences, and to indices of minor psychiatric morbidity (the General Health Questionnair and the Zung Depression Scale). Life event frequency, but neither measure of morbidity, distinguished between persons with different lengths of residence in Canberra. It can be suggested that a random sample, containing an under-representation of migrants and persons moving from rural to urban environments, in whom the transition in shifting place of residence would be expected to be greatest, is an inappropriate sample to test hypotheses concerning length of residence and psychiatric morbidity, Future studies should give due emphasis to the adequate inclusion of these groups of persons.

Australia↗

Circulating immune complexes in patients following clinically curative resection of colorectal cancer.

Sixty-nine patients have been followed prospectively after curative resection of Dukes-Kirklin B-2 or C colorectal cancer. Serial plasma samples were studied in selected patients to determine changes in circulating immune complex concentrations (CIC) following primary tumor resection, and to compare serial plasma CIC and carcinoembryonic antigen (CEA) levels. CIC was determined in an average of seven serial samples per patient by inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). CEA assays were performed by the Hanson Z-gel method. Two distinct patterns of serial CIC have emerged. In seven patients with no known tumor recurrences, serial CEA levels and CIC oscillated regularly and were inversely related. In seven of eight patients whose tumors recurred, both CEA and CIC rose together. In three patients with elevated plasma CEA levels due to inflammatory bowel disease, serial Ag-Ab complex concentrations did not vary, nor did separated Ag or Ab fractions inhibit ADCC. These data suggest that, in patients following curative resection of colorectal cancer, serial changes in circulating immune complexes may discriminate between transient CEA elevations which occur despite no known tumor recurrence and tumor recurrence which is beyond the capacity of adequate host antitumor defense.

Adenocarcinoma↗

Transient carcinoembryonic antigen (CEA) elevations following resection of colorectal cancer: a limitation in the use of serial CEA levels as an indicator for second-look surgery.

In a previous study, other investigators recommended second-look surgery for colorectal cancer primarily on the basis of plasma carcinoembryonic antigen (CEA) rises and prepared a nomogram for ready recognition of these "significant" increases. We found 25 patients whose CEA levels met the recommended criteria for significance; however, in 9 of these patients the rises were transient. Eight had no clinical evidence of recurrent cancer and they might have had negative second-look surgery had this been done because of CEA rises alone. The use of the CEA nomogram merely eliminated laboratory variation as a cause of the CEA rise. It did not, however, rule out biologic causes of CEA rises, other than that of cancer, especially benign liver disease. We were unable to differentiate benign from malignant rises on the basis of CEA changes alone. Preoperative CEA values helped to separate the two rises. Transient rises usually began earlier. Malignant CEA rises were more likely to be exponential. The rate of rise alone did not discriminate between the two rises. Thus, although serial CEA levels were helpful in making the decision for reexploration, they did not substitute for complete clinical assessment.

Carcinoembryonic Antigen↗

Persistent sciatic artery and sciatic artery aneurysm: a hazard in hip surgery.

During a posterior approach to the hip joint great caution must be exercised in protecting a persistent sciatic artery. Inappropriate trauma could either cause peripheral embolization, propagation of mural clots, or rupture. Prior to ligation, arteriography is critical because, despite the presence of strong femoral or popliteal pulses, the persistent sciatic artery may be the main conduit to the lower extremity.

Aged↗