Search

Accumulated evidence suggests that increased body iron stores may increase the risk of colorectal cancer, possibly via catalyzing oxidation reactions. We examined the relationship between iron status and colorectal cancer in a case-control study nested within the New York University Women's Health Study cohort. For 105 incident cases of colorectal cancer with an average follow-up of 4.7 years and 523 individually matched controls, baseline levels of serum iron, ferritin, total iron binding capacity (TIBC) and transferrin saturation were determined as indicators of body iron stores, and total iron intake was assessed based on their diet and supplement intake. Overall, there were no associations between the risk of colorectal cancer and any of these indices except for serum ferritin, which showed a significant inverse association. When analyzed by subsite, there was an increasing trend in risk of cancer of the proximal colon with increasing total iron intake (p-value for trend = 0.04). In addition, a significantly increased risk of colorectal cancer associated with higher total iron intake [odds ratio (OR) = 2.50; 95% confidence interval (CI): 1.06-5.87] was observed among subjects with higher intake of total fat. Our results do not support a role of increased body iron stores in the development of colorectal cancer, but suggest that luminal exposure to excessive iron may possibly increase the risk in combination with a high fat diet.

Serum enzymes have not proved useful in evaluation of patients with early colon cancer, but certain enzymes such as transpeptidase, phosphohexone isosomerase, or 5'-nucleotidase have been of assistance in following the course of the disease, particularly in patients with metastatic spread to the liver. Attempts have been made to improve the utility of enzyme analysis in colon cancer by examination of enzyme patterns in colon biopsy specimens, feces, and colon washings. These studies, which will be summarized, are of importance in the possible development of diagnostic tools and as probes in the understanding of the etiology of colon cancer. The technical problems in carrying out these assays in humans, as well as the significance of the activity of aryl sulfatase, beta-glucuronidase, beta-glucosidase, lactic dehydrogenase, glucose-6-p-osphate dehydrogenase, and other enzymes will be considered.

An antigen immunologically related to mouse mammary tumor virus (MuMTV) and the major envelope glycoprotein, gp52 of MuMTV, was identified in tissue sections of human male and female mammary carcinomas using the peroxidase-antiperoxidase technique. The specificity of the reaction was established by absorption studies. Positive reactions with the gp52 antiserum were seen in mouse and human mammary carcinomas, but not in normal mammary tissues, mammary tissues with benign diseases and in other primary malignant neoplasms. Almost all (32/36, 89%) male mammary carcinomas were positive for the gp52 related antigen. A lesser proportion of tumors among female patients (14/50, 28%) were positive. The gp52 positive tumors were significantly larger than the gp52 negative tumors in female patients (P less than 0.05). Gp52 positive tumors were also larger than gp52 negative tumors in male patients, but the difference was not statistically significant. Gp52 reactivity was also detected in metastatic mammary carcinoma in axillary lymph nodes of male and female patients. The presence of gp52 related antigen was not apparently related to tumor grade or lymphocytic infiltrate in the primary tumor. The data do not permit a firm conclusion regarding nodal status in men; no correlation of gp52 activity and nodal status in women was evident. These results indicate that mammary carcinomas in men as well as in women have an antigen related immunologically to MuMTV gp52. Other than tumor size, the antigen seems to be unrelated to major prognostic factors. The significance of the antigen with respect to etiologic features and prognosis in breast cancer remains to be determined.

In colon cancer biologic markers have been successfully utilized to follow the course of disease, to evaluate response to therapy, and to predict recurrence. With the exception of occult blood measurements, there has been little success in adopting markers to early diagnosis. The role of CEA in predicting the course of the disease is considered, as well as the utility of combining serum enzyme measurements and carcinoembryonic antigen (CEA) assays for these purposes. Aryl sulfatase B has been correlated to the stage of the disease, and enzymes involved in the metabolism of glycoproteins (sialyltransferase and glucosyltransferase) may be of importance in monitoring colon cancer. Polyamines have been observed in blood and urine of patients with a variety of cancers and their presence during therapy in increased amounts may reflect cancer cell death as well as tumor growth. Their use in diagnosis and chemo-therapeutic monitoring in colon cancer has not yet been established. Another area of possible use of biologic markers is their measurement in colon washings. This is discussed in regard to the assay of CEA and enzymes in colonic lavage.

Flow cytometry studies of the DNA distribution of tumor cells from 92 human breast cancers showed measurable aneuploidy (hyperploidy) in 83 cases (92%). The DNA ploidy values were unimodal in each case, but there was a bimodal distribution for the entire series. One group of tumors had a diploid or near diploid DNA distribution and a second group had ploidy levels from triploid to tetraploid or higher. The tumors with lower DNA ploidy (at or near diploid) tended to be histologically low grade, cytologically more orderly and estrogen-binding positive; those with higher DNA ploidy were more likely to be higher grade, more anaplastic, and estrogen-binding negative.

Serum zinc, copper, and the Cu/Zn ratio were evaluated in 80 patients with breast lesions prior to surgery. There were 37 patients with benign and 43 with malignant breast lesions. There was no evidence of weight loss, impaired appetite, or change in eating pattern in any of the patients. There was a statistically significant difference for the mean SCL and Cu/Zn ratio between controls, age 66-94, and patients with malignant breast lesions. This difference was also observed between the ages of 20-45 and 66-94 among controls, suggesting that this is age related rather than disease related. The range of distribution for SZL and SCL were similar for all groups studied. Neither SZL, SCL, or the Cu/Zn ratio were of value in discriminating between controls and patients with benign or malignant breast lesions. We were unable to demonstrate the value of these parameters as markers of disease activity in patient with benign or malignant breast lesions.

Lactic dehydrogenase (LDH) isoenzymes were measured in the cerebrospinal fluid (CSF) patients suffering a variety of cancer-related neurologic problems. LDH-5 isoenzyme as a percentage of total LDH activity was abnormally elevated (above 10 to 15%) in leptomeningeal infiltration by carcinoma (breast carcinoma, lung carcinoma, and malignant melanoma) but not in other types of CNS metastases. Abnormal LDH isoenzyme patterns were also seen with CSF infections in which a granulocytic pleocytosis was present. In the absence of infection, an elevated LDH isoenzyme 5:1 ratio suggested leptomeningeal tumor and, when used with other CSF markers (beta-glucuronidase and CEA), LDH, isoenzymes aid in early detection of this metastatic neoplastic process. They may also help to differentiate leptomeningeal tumor from other chronic meningitides. Measurement of CSF markers also aids in assessing the effectiveness of treatment since marker levels often vary with the clinical course.

813 patients were prospectively studied to examine the influence of family history and the prior use of exogenous hormones as covariables in the subsequent expression of estrogen receptor protein (ERP) in the primary tumor of patients with breast cancer. Cases were divided by menstrual status: there were 385 pre- and perimenopausal and 428 postmenopausal patients. The influence of prior exposure to estrogen replacement therapy (ERT) in postmenopausal patients or oral contraceptives (OCs) in pre- and perimenopausal patients on tumor ERP was analyzed by controlling for family history: none 1st degree (mother or sister) 2nd degree (grandmother or aunt) or both 1st and 2nd degree relatives. The results showed no influence of the prior use of ERT in postmenopausal women on subsequent tumor ERP. Among pre- and perimenopausal women those with a family history of breast cancer in only a 1st degree relative showed a borderline significant association between prior OC usage and subsequent tumor ERP. The use of OCs was consistently associated with ERP negative tumors (9/9) whereas of 29 patients who had prior OC exposure 17 had ERP negative tumors (P=0.04 Fishers Exact Test). Analysis of the prior exposure to OCs verified with the primary physician care or pharmacist showed that these patients first used OCs at the mean age of 32.2 years had used OCs for a mean duration of 41.9 months and stopped OC use a mean of 79.5 months before being diagnosed as having breast cancer. These results suggest that in a subset of patients with breast cancer and a 1st degree relative who only had breast cancer prior exposure to OCs may influence the subsequent ERP status of the tumor. This is not due to exogenous estrogen saturation of receptors as there was a long latent period between exposure and diagnosis. Alternative hypotheses as to the mechanism of selection of subsequent tumor ERP may be either inhibition of ERP positive preneoplastic or tumor cell clones early in the evolution of the tumor or early selection of a tumor capable of endogenous estrogen synthesis with receptor saturation. (authors modified)

A summary is presented of those organ specific enzyme assays traditionally used in evaluation of the patient with cancer. In addition, the use of certain serum enzymes such as gamma-glutamyl transpeptidase, phosphohexose isomerase or 5'-nucleotidase as aids in following the course of the disease, particularly in patients with metastatic spread to the liver is outlined. Also considered is the utility of enzyme analysis in biopsy tissue, biologic fluids, and washings of body cavities. Newer enzymes are considered which might, in the future, be developed as diagnostic tools or as probes for the understanding of the etiology of cancer.

The reliability of lipid-bound sialic acid (LSA) as a marker in breast cancer was evaluated in 78 normal subjects, 106 patients with benign breast disease, 64 patients with primary operable breast cancer, and 61 patients with recurrent metastatic breast cancer. LSA levels were determined before and after mastectomy and during chemotherapy in selected patients to determine the value of LSA in monitoring therapy and predicting response. LSA levels greater than 20 mg/dl were not seen in normal subjects but were present in patients with benign breast disease (13%), primary breast cancer (47%) and recurrent metastatic breast cancer (62%). LSA levels decreased after initiation of chemotherapy and remained low in patients clinically disease-free. Recurrences were associated with elevated LSA in patients failing chemotherapy or endocrine ablative surgery. LSA measurements appeared to be of limited value in the detection of breast cancer but serial measurements may be useful in assessing disease progression and identifying patients resistant to therapy. Cancer 50:1815-1819, 1982.

By contract with the National Cancer Institute, the accuracy of diagnostic techniques was assessed in 184 patients suspected of having pancreas cancer. Of 138 patients who were operated upon, 89 were found to have pancreas duct cancer, 30 had cancer of a different site of origin in the head of the pancreas region and in 19 there was no evidence of cancer at operation. All of the 46 patients who were not operated upon, 13 proven to have cancer and 33 patients discharged as free of cancer, were followed in our clinic. The majority of our patients presented with signs and symptoms of biliary obstruction. Computerized transaxial tomography (CTT) gave a "correct" diagnosis in 31 of 33 patients (94%) with proven cancer, there were 2 patients with a false negative report and a false positive diagnosis occurred in 8 of 20 patients (40%) without cancer. Celiac angiography (CA) gave a correct diagnosis in 78 of 94 patients (83%) with cancer, a false negative in 17%, and a false positive in 32%. 76Selenomethionine pancreas scan correctly diagnosed 27 of 36 patients (75%) with cancer, gave a false negative in 25% and a false positive in 31%. Ultrasonography gave a correct diagnosis in 18 of 27 patients with cancer (67%), a false negative in 33% and a false positive in 28%. Endoscopic retrograde cholangiopancreatography diagnosed correctly 8 of 11 cases (73%) of cancer, there were false negative diagnoses in 3 cases (27%) and false positives in 3 of 14 patients (21%). Duodenal aspiration techniques gave a very low percentage of correct diagnoses. Chronic pancreatitis most commonly gave rise to a false positive diagnosis. Serum alkaline phosphatase was elevated in 82% of patients, gave 18% false negatives and 33% false positives. Carcinoembryonic antigen (CEA) was elevated (greater than 2.5 ng/ml) in most of the pancreas cancer patients but also in patients with other cancers and with non-cancerous diseases. In our hands, CTT, CA, alkaline phosphatase, 75Se-methionine and ultrasonography, in descending order, have given the highest percentage of correct diagnoses but false positive and false negative diagnoses prevented any single test from being conclusive.

The administration of CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone) results in profound alterations in hormonal profiles of premenopausal women due to a reduction in ovarian and adrenal secretion of estrogens and androgens. Cytotoxic chemotherapy results in ovarian suppression as documented by decreases in estradiol with concomitant elevations in pituitary gonadotrophins, whereas the addition of prednisone to the cytotoxic regimen results in significant decreases in androgen levels due to adrenal suppression. In postmenopausal women, CMFVP also results in significant decreases in estrogens and estrogen precursors due to suppression of adrenal steroid metabolism. Continuous low-dose prednisone administration during cytotoxic chemotherapy appears to be more effective than an intermittent high-dose schedule in achieving and sustaining adrenal suppression. However, complete elimination of adrenal steroidogenesis does not occur in all cases since measurable amounts of adrenal steroids remain in the serum throughout chemohormonal therapy. The administration of tamoxifen plus CMFVP is associated with hyperestrogenemia in younger premenopausal patients which persists until the onset of ovarian suppression.

Analysis of estrogen receptor protein (ERP) was carried out on 784 patients with primary breast carcinomas. Significant relationships were found with the following epidemiologic features; age at diagnosis, menstrual status, race, and use of exogenous hormones (contraceptive and menopausal estrogens). Patients taking either type of hormone at diagnosis had lower median total ERP binding levels. Although the data do not explain how recent hormone usage affects tumor ERP, it seems advisable to discontinue these hormones as early as possible before a breast biopsy because they may cause spuriously low ERP levels. Correlation with pathology variables confirmed most prior observations relating to tumor type, histologic grade, and lymphocytic infiltrate. However, in this large series, infiltrating lobular carcinomas were not ERP-positive more frequently than duct carcinomas to any significant degree. The pattern of progesterone receptors (PRP) did not vary significantly with menstrual status, but in other respects correlations of epidemiologic and pathologic variables were similar for ERP and PRP.

Flow cytometry analysis of cell cycle distribution was carried out on acridine-orange-stained cell suspensions freshly prepared from carcinoma of the breast of 90 women, and compared with control, benign breast specimens from 10 women. There was a significantly greater proportion of cells in S (9.1% +/- 5.8) and G2 + M (8.0 +/- 6.0) phases of the cycle in breast cancer specimens than in the S (1.5% +/- 0.6) and G2 + M (2.5 +/- 0.9) phases of the cycle in benign, control specimens of breast tissue. Great variation was noted among the breast cancers, with medullary carcinomas having the highest percentage of cells in S + G2 + M, and papillary, tubular, colloid and well-differentiated duct carcinomas having the lowest. Tumors from premenopausal women classified as estrogen receptor negative had significantly more cells in S + G2 + M than did tumors from postmenopausal women that were estrogen-receptor positive.

During therapeutic trials with E. coli L-asparaginase in 131 children and 143 adults with neoplastic disease the following signs of toxicity have been observed: fever, nausea and vomiting, weight loss, somnolence, lethargy, confusion, hypolipidemia, hyperlipidemia, hypoproteinemia, abnormal liver function tests, fatty metamorphosis of the liver, pancreatitis (in rare instances), azotemia, granulocytopenia, lymphopenia, thrombocytopenia, and hypersensitivity reactions. While these effects have been moderately severe and reversible in most instances, some patients have shown dangerous degrees of toxicity. This has been the case most frequently in adult patients receiving a dose of 5000 IU/kg/day.

The distribution of γ-aminobutyric-α-oxoglutarate transaminase (GABA-T) has been studied in mouse brain by histochemical visualization on sections, quantitative determination in grossly dissected brain regions, and in subcellular fractions prepared from whole brain homogenates. The results indicate that GABA-T is predominantly a mitochondrial enzyme and that its concentration is particularly high in brain stem areas. The results are discussed in relation to the overall function of the GABA system in the CNS.

Eleven specimens of breast lesions obtained from 10 male patients were analyzed for estrogen receptor protein (ERP). Three patients (ages 49, 77, 82 years) had infiltrating duct carcinomas with no axillary metastases. ERP in each of these was positive. Eight specimens with gynecomastia, one of which was obtained from the 77-year-old patient with carcinoma in the same breast, were also analyzed. Of these ERP was positive in a 59-year-old man who had cirrhosis of the liver; two patients with borderline ERP had hepatitis and testicular seminoma, respectively. No relationship between histopathologic features of the lesions and ERP results was found and it is too early to relate these ERP studies to prognosis in these patients. Review of available literature, including our cases, reveals that six of eight male breast carcinomas were ERP-positive.