Wanda B. Mackinnon

Proteolipid identified by magnetic resonance spectroscopy in plasma of a patient with borderline ovarian tumour

Magnetic resonance spectroscopy (MRS) can identify abnormal lipoproteins in the plasma of patients with premalignant and malignant tumours. Proteolipid complexes, 8-11 nm and 25-28 nm in size, were isolated from the plasma of a patient with a borderline ovarian tumour. These complexes, which generated a characteristically long MRS T2 relaxation value (greater than 400 ms), were disrupted by ribonuclease. None of the conventional lipoproteins had a T2 value above 160 ms. Chemical analysis of the proteolipid complexes showed a 20% glycolipid component, and MRS identified a fucosylated molecule as the origin of the long T2 value. 9 months after resection of all tumour, a visible lipoprotein band, possibly lipoprotein (a), persisted in the plasma but neither the long T2 relaxation value nor the 8-11 nm or 25-28 nm particles were present. The long T2 relaxation value in the MRS profile, found in isolated proteolipid and unfractionated plasma and serum of other patients with carcinoma of the ovary and colon, provides a non-invasive method of assaying for cancer.

The Use of Proton MR in Cancer Pathology

Publisher Summary This chapter describes the use of proton MR in cancer pathology. Water-based MRI is, at present, independently unable to identify the pathology of human tumors. The literature and work in this domain indicate that by studying carefully controlled model systems and excised human tissues, 1 H MRS can extract chemical information relating directly to the pathology. In addition, by tailoring data acquisition and processing parameters to report specifically on those molecules of known diagnostic relevance, 1 H MRS can diagnose invasive cancer in many organs ex vivo and some in vivo . 1 H MRS has the potential to provide an independent modality that can (1) report on the presence of invasive or preinvasive neoplastic cells in biopsy specimens, (2) detect the microfoci of metastatic cells missed by routine histopathology, and (3) provide a precise diagnosis to aid in the decision on treatment and subsequent patient management. Cancer can be diagnosed by 1 H MRS if the pathological criteria are linked to specific chemical changes ascertained from intact cells and tissues. This concept was demonstrated by the cervix program where CSI ( ex vivo ) not only defined the pathology of the tissue but also provided a spatial map of the diseased areas.

Two-Dimensional Proton Magnetic Resonance Spectroscopy for Tissue Characterization of Thyroid Neoplasms

Abstract. We have previously demonstrated that one dimensional (1D) proton ( 1 H) magnetic resonance spectroscopy (MRS) can distinguish normal thyroid tissue from thyroid carcinoma using a spectral ratio of peak intensity at 1.7 ppm/0.9 ppm. Two dimensional (2D) 1 H-MRS allows identification of specific molecules that have overlapping peaks in the 1D-MR spectrum. Specimens from 93 consecutive thyroid nodules were examined using 2D 1 H-MRS on a Bruker AM-360 wide-bore spectrometer. There was a progressive increase in lipid cross peaks assigned to di-/triglycerides when comparing colloid/hyperplastic nodules to follicular adenoma, and adenoma to carcinoma. A specific cross peak attributable to cholesterol/cholesteryl esters was commonly seen in carcinomas. In contrast, two unassigned cross peaks unique to the thyroid were more prevalent in benign lesions. There was an overall increase in cross peaks attributable to cell surface fucosylation in carcinoma when compared to benign lesions, although the fucose spectral pattern was not specific for cancer. On this basis, a spectral ratio of peak intensity at 2.05 ppm/0.9 ppm more clearly distinguished benign follicular adenoma from carcinoma. 2D 1 H-MRS thus identifies chemical changes that allow more specific tissue characterization of thyroid neoplasms.

A PROTON MAGNETIC RESONANCE SPECTROSCOPY STUDY OF AGING AND TRANSFORMED HUMAN FIBROBLASTS

Proton magnetic resonance spectroscopy (1H MRS) has been used to monitor changes occurring during aging and transformation in human lung fibroblasts. Aging was studied in MRC-5 cells from nonsenescent (early passage) to presenescent (late passage) and senescence. Nonsenescent cells infected with SV40 virus (pretransformed) were monitored through crisis and subsequent immortalization. Aging changes were observed with one- and two-dimensional MR spectra. Cholesterol and lipid resonances were significantly increased from nonsenescent cultures to senescence. These changes could be caused by chemical or structural changes in the plasma membrane or in intracellular lipid pools. In contrast, choline levels rose from nonsenescent to presenescent cells but at senescence dropped to that of nonsenescent cells. Increased choline levels are often associated with increased cellular proliferation. After SV40 infection of MRC-5 cells there was an increase of cholesterol and lipid levels that peaked at crisis. Newly immortalized cells exhibited a drop in cholesterol and lipid to nonsenescent cell levels, but these rose again in established immortalized cells. In contrast to presensescent cultures, the levels of choline gradually increased from pretransformed to crisis phase but still continued to rise after immortalization. Thus, 1H MRS illustrates similarities in lipid behavior at senescence and crisis, whereas the choline levels are different.

MALIGNANCY-RELATED CHARACTERISTICS OF WILD TYPE AND DRUG-RESISTANT CHINESE HAMSTER OVARY CELLS

&NA; Chinese hamster ovary (CHO) cell lines are a very popular cell model for a wide range of studies but are often misused experimentally as a substitute for normal cells. Although CHO was originally derived from normal tissue, the cell lines studied here, including the parental wild type, have many characteristics which indicate that they have undergone malignant transformation. Biological properties associated with malignancy were investigated in this study on wild type CHO cells and 4 drug resistant sublines, EOT, Col R‐22, Pod R11‐6, and Vin R‐1. We report evidence of tumorigenicity in experimental animals, invasive capacity, in vivo and in vitro, protease release by 2 of the cell lines, features related to drug resistance in the mutant sublines, and numerical and structural chromosomal abnormalities.