Assessment of urinary beta-core fragment of human chorionic gonadotropin as a new tumor marker of lung cancer

BACKGROUND: Some patients with lung cancer have been found to have elevated levels of serum immunoreactive human chorionic gonadotropin (hCG)/hCG beta (IR-beta), but it is uncertain whether it would be valuable as a tumor marker. Recently, IR-beta has been demonstrated to consist of at least three different molecules, intact hCG, free hCG beta, and hCG beta-core fragment (beta-CF), in body fluids. In this study, the authors qualitatively analyzed IR-beta in the serum and urine of patients with lung cancer and assessed its clinical usefulness as a tumor marker. METHODS: Highly sensitive and specific enzyme immunoassays were established to measure intact hCG, free hCG beta, and beta-CF in the serum and urine of patients with lung cancer. RESULTS: Of 99 patients with lung cancer, almost half of the patients achieved positive values of IR-beta in the urine, although only 12 had elevated values of IR-beta in the serum. The greater part of the elevated urinary IR-beta was identified to be beta-CF by gel chromatography on Sephadex G-100 (Pharmacia LKB Biotechnology, Tokyo, Japan), leading the authors to assess its usefulness as a tumor marker for lung cancer. Based on the cutoff value (0.2 ng/mg of creatinine) from healthy subjects, the overall positive rate of urinary beta-CF for lung cancer was 48.5% (48 of 99 patients). The incidence of the marker increased with stage of disease, from 35.7% (15 of 42) in Stage I and 35.7% (5 of 14) in Stage II to 62.5% (20 of 32) in Stage III and 72.7% (8 of 11) in Stage IV. These positive rates exceeded or equaled those of the serum tumor markers, carcinoembryonic antigen, and squamous cell carcinoma (SCC)-related antigen, measured simultaneously in the same patients. The author were encouraged that there was no significant difference in the positive rates of urinary beta-CF between two major types of lung cancer: adenocarcinoma (49.2%) and SCC (45.2%). Immunohistochemical study revealed positive staining of IR-beta in the cancer tissues from 5 of 12 patients with elevated levels of IR-beta, in which most of the positive cases had the elevated levels of serum free hCG beta (> 0.5 ng/ml) and/or urinary beta-CF (> 1.0 ng/mg of creatinine). CONCLUSIONS: Ectopic production of IR-beta by lung cancer is not rare, and urinary beta-CF might be a potential tumor marker of lung cancer.     

Evaluation of serum neural cell adhesion molecule as a new tumor marker in small cell lung cancer

BACKGROUND: Small cell lung cancer (SCLC) is distinguished from other histologic types of lung cancer by possessing a variety of neuroendocrine properties. Neuron-specific enolase (NSE) is the most frequently elevated tumor marker for patients with SCLC at diagnosis. To assess the value of neural cell adhesion molecules (NCAM), another possible tumor marker for small cell lung cancer, NCAM was evaluated in the sera of patients with histologically confirmed SCLC in two prospective multicenter trials. METHODS: The study includes 221 patients with SCLC, normal human blood donors (n = 34), patients with benign lung disease (n = 53), and patients with non-small cell lung cancer (n = 28). NCAM was determined by means of an enzyme immunoassay, NSE by a radioimmunoassay. RESULTS: The data show the following: (1) 51% (113 of 221) of all patients with SCLC had NCAM levels higher than 20 U/ml, 34% (75 of 221) had NSE levels higher than 25 ng/ml; (2) levels of both markers significantly differ between limited and extensive disease patients; (3) patients with pathologic NCAM and NSE levels have significantly shorter survival times; (4) a positive correlation between pretreatment NSE and NCAM levels was found (n = 221, r = 0.60); and (5) a correlation between serum marker levels and clinical status was found in follow-up studies of 19 patients. CONCLUSIONS: From these data, it is concluded that NCAM is, along with NSE, a potential tumor marker for SCLC.     

Mechanism of increased serum cytokeratin 19 fragment levels in patients with diabetic nephropathy as a model of chronic renal failure

We examined serum and urinary cytokeratin 19 fragment (CYFRA 21-1) levels in patients with diabetic nephropathy as a model of chronic renal failure, to investigate the mechanism of increased serum CYFRA 21-1 levels in chronic renal failure. Serum and urinary CYFRA 21-1 levels in non-insulin-dependent diabetes mellitus (NIDDM) patients with abnormal urinary immunoglobulin G (IgG) levels (>1.1 mg/g x Cr, n=126) were higher than those with normal urinary IgG levels. In NIDDM patients with normal urinary IgG levels (n=81); the urinary albumin or transferrin levels were not related to serum or urinary CYFRA 21-1 levels. We speculate that the increased serum CYFRA 21-1 levels contribute to metabolic abnormality in the kidney itself rather than the decreased urinary excretion per se, and that increased urinary CYFRA 21-1 levels are found in advanced cases of diabetic nephropathy with destruction of the size barrier.     

Clinical usefulness of serum PIVKA-II levels determined by ECLIA system as a tumor maker for hepatocellular carcinoma

PIVKA-II is well known as a tumor maker of hepatocellular carcinoma (HCC). We measured serum PIVKA-II concentrations with a commercially available PIVKA-II immunoassay kit (Picolumi PIVKA-II: Eisai Co., Ltd., Tokyo) using Electrochemiluminescence Immunoassay (ECLIA). ECLIA system is a novel immunoassay system using a Ruthenium (II) Tris (bipyridyl) luminesced by electric energy. Cut off value was 40 mAU/ml by receiver-operating characteristic curves as a tumor maker for HCC. Eighty-nine out of 142 (62.2%) patients with HCC had elevated serum PIVKA-II levels and seventeen out of 36 (47.2%) patients whose tumor size was below 2 cm in diameter showed high PIVKA-II levels. We determined the serial changes in serum PIVKA-II levels of two patients with HCC following initial therapy. In these patients, elevations of serum PIVKA-II levels determined by ECLIA system preceded the HCC relapse detected by imaging diagnostic procedures. In summary, this assay system is suitable for detecting small increases in PIVKA-II concentrations. Determination of PIVKA-II by this assay system is found to be useful for the early detection of HCC.     

Significance of serum beta-hCG as a tumor marker for stomach carcinoma

We performed BAEP study to evaluate acoustic nerve involvement in 102 patients affected by peripheral neuropathies of different etiology, predominantly hereditary and inflammatory acquired neuropathies. Prolonged latency of early waves, indicative of slowing in VIII nerve conduction, was found in a high percentage of cases. Abnormalities were far more frequent (44% vs 14%) and severe in patients with demyelinating rather than axonal neuropathy. Among demyelinating neuropathy, the most severe latency delay was found in Hereditary Motor and Sensory Neuropathy type III. The pattern of acoustic nerve involvement differed slightly between Hereditary Motor and Sensory Neuropathy type I and acquired inflammatory demyelinating polyradiculoneuropathy, perhaps reflecting different pathogenetic mechanisms and different sites of VIII nerve demyelination.     

Anal canal cancer diagnosis: usefulness of serum tumor markers

Many paper based chart recorders still suffer from paper uptake systems for the collection of chart record that operate inefficiently or haphazardly. An efficient low cost paper minder using 1.2 mm diameter stainless steel wire for the Siemens-Elema AB Mingograph 7, has been developed. This wire pivots from the end of the chart viewing table and provides an effective force to redirect paper into the standard collecting basket over the entire range of paper speeds.     

Telomerase activity as a novel marker of lung cancer

Telomerase activity is found in more than 80% of human malignant neoplasms, including lung cancer. Markers with high incidence in malignant samples and very low incidence in benign samples are useful in clinical diagnosis of cancer. Thus, telomerase activity in clinical materials may become a novel tumor marker of existing lung cancer cells. Moreover, since activation of telomerase is associated with cellular immortality and its activity level is quite different between lung cancer tissues, the activity level may become an indicator of some biological features in lung cancer.     

ADP-ribosylation of serum proteins: evaluation as a potential tumor marker

The low-affinity p75 receptor for nerve growth factor (p75NGFR) has been implicated in mediating neuronal cell death in vitro. A recent in vitro study from our laboratory showed that the death of sensory neurons can be prevented by reducing the levels of p75NGFR with antisense oligonucleotides. To determine if p75NGFR also functions as a death signal in vivo, we have attempted to reduce its expression in peripheral sensory neurons by applying antisense oligonucleotides to the proximal end of the transected sciatic or median and ulnar nerves. We report here that antisense oligonucleotides, when applied to the proximal stump of a transected peripheral nerve, are retrogradely transported and effectively reduce p75NGFR protein levels in sensory neurons located in the dorsal root ganglia. Furthermore, treatment of the proximal nerve stump with antisense p75NGFR oligonucleotides significantly reduced the loss of these axotomized sensory neurons. These findings further support the view that p75NGFR is a death signaling molecule and that it signals death in axotomized neurons in the neonatal sensory nervous system.     

Level of sialic acid in blood serum as a tumor marker]

In the recent quick development of cancer diagnostic methods, attention of researchers is focused onto tumor-derived compounds as possible markers of neoplasia. In this article we have reviewed researchers' opinions about sialic acid as a tumor marker. According to majority of researchers, blood sialic acid may be regarded as a useful marker for a variety of cancers although its specificity is not high.     

The usefulness of mediastinoscopy for primary lung cancer

The usefulness of mediastinoscopy for lung cancer was retrospectively evaluated for the aspect of prognosis. The subjects were 421 patients with primary lung cancer except exploratory thoracotomy. In the MD(+) group, there was no difference in prognosis between right and left sided thoracotomies, but in the MD(-) group there was a tendency for poorer prognosis in the left-sided thoracotomy (p < 0.1). In the right-sided thoracotomy, there was no difference of prognosis between the MD(+) group and MD(-) group. On the contrary, in the left-sided thoracotomy there was a statistically better prognosis in the MD(+) group than in the MD(-) group (p < 0.05). In the left-sided thoracotomy group, there was a statistically better prognosis in the MD +) group than in the MD(-) group in the pN 0 or pN 1 group (p < 0.01), but there was no difference of prognosis in the pN 2 group. In lung cancer of the left side, the mediastinal lymph node dissection would be more incomplete because of the presence of the aorta and the mediastinal lymph node metastasis would tend to be missed. Mediastinoscopy gives the right diagnosis of mediastinal lymph node metastasis and an accurate staging of lung cancer. Mediastinoscopy is very useful especially in the left-sided lung cancer.     

CYFRA 21-1 enzyme-linked immunosorbent assay. Evaluation as a tumor marker in non-small cell lung cancer

BACKGROUND: The CYFRA 21-1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21-1 is a sensitive and specific tumor marker for non-small cell lung cancer. METHODS: CYFRA 21-1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer. RESULTS: The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21-1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivity. The median level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p<0.001). The serum level and sensitivity of CYFRA 21-1 were well correlated with staging and tumor size in squamous cell carcinoma. The CYFRA 21-1 values were measured for monitoring progression of disease in 20 patients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients with progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was observed in patients with stabilized disease (p>0.1). CONCLUSION: For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.     

Serum levels of cytokeratin 19 fragments in cervical cancer

The objective of this study was to compare the efficacy and tolerability of two new antiepileptic drugs, lamotrigine (LTG) and vigabatrin (GVG) in everyday clinical practice. A comprehensive retrospective survey of a computerized data base and hospital case notes was carried out at the Mersey Regional Epilepsy Clinic (MREC), Liverpool, which services a population of 3 million in the North West of England. The study comprised 333 out-patients with refractory epilepsy exposed to LTG and GVG forming a subset in a total population of 2250 patients with epilepsy held on a comprehensive database. The main outcome measures were duration of treatment with each drug described by a Kaplan-Meier survival curve, seizure control determined by a 50% decrease in seizure frequency and freedom from seizures, and incidence of adverse drug effects leading to discontinuation. The Kaplan-Meier curve indicated a 57% probability of patients continuing to take LTG and 43% GVG after 40 months. A 50% improvement in seizure control followed the addition of LTG in 45% of patients, with 10% seizure free, compared with 32% and 6%, respectively after the addition of GVG. LTG was discontinued because of adverse events (most frequently skin rash) in 15% of patients compared to GVG in 25% (particularly because of personality disturbance and psychiatric disorder). Both LTG and GVG are effective new AEDs in patients with refractory epilepsy, treated in a tertiary referral out-patient setting. LTG has a broader spectrum of antiepileptic efficacy for patients with both partial and idiopathic generalized seizures, whereas GVG should be reserved for patients with partial seizures at low risk of psychiatric disorder.     

Mutations of the P53 tumor suppressor gene as clonal marker for multiple primary lung cancers

OBJECTIVES: Second primary lung cancers are prevalent after treatment for initial lung cancer, and the lung is also one of the most frequent sites for recurrence after removal of early-stage lung cancer. The objective of the present study is to clarify the clonal origin of the second tumor with the p53 gene mutation used as a clonal marker. METHODS: Of 794 consecutive patients who underwent pulmonary resection for primary lung cancer from 1980 to 1993, 22 required second pulmonary resection during the follow-up period, with a median interval of 38 months. We examined 16 of these patients for mutations of the p53 gene occurring in exons 5 through 8 by the polymerase chain reaction/single strand conformation polymorphism method. Differential diagnosis was also made on a morphologic basis, considering the degree of cellular differentiation and cytologic subtypes. RESULTS: Nine of the 16 patients analyzed had at least one p53 mutation in their tumors. We were thus able to make molecular diagnoses for these patients. The mutational status of the p53 gene was discordant in all nine patients, suggesting a different clonal origin despite the fact that six of them had almost identical histologic features. CONCLUSIONS: Analysis of p53 gene mutations was thus useful in distinguishing second primary lung cancers from recurrent tumors. The observed heterogeneity of p53 status was also in line with the "field cancerization" concept.     

Increase of serum tumor marker concentrations by interferon-alpha

BACKGROUND: The effect of infection by Helicobacter pylori on gastric physiology in duodenal ulcer subjects is controversial. There is evidence that the infection is associated with abnormalities in gastrin homeostasis. Consistent changes in pentagastrin-stimulated acid secretory status have proved difficult to establish. This may be because patients have been studied too soon after Helicobacter pylori eradication. AIMS: To study the immediate and longer term effect of Helicobacter pylori eradication on basal and pentagastrin-stimulated acid secretion in duodenal ulcer subjects. PATIENTS AND METHODS: Patients with active duodenal ulcer disease were studied. Ulcers were healed with sucralfate 2 g bd or ranitidine 300 mg nocte. Helicobacter pylori eradication was attempted with bismuth-based "Triple Therapy", and the nine patients in whom the organism was successfully eradicated were followed and studied over the 12-month period. Acid secretion was studied at entry (prior to the initiation of therapy), following healing, following eradication and 12 months later. Basal, low dose (0.1 microgram/kg) and high dose (6 micrograms/kg) pentagastrin-stimulated acid secretion was determined. RESULTS: Whilst there was a tendency for basal and low dose-stimulated acid secretion to fall following eradication, in this study only the reduction in high dose-stimulated acid secretion achieved significance following eradication (entry mean = 59.6, post eradication mean = 49.6, p < 0.03). This effect of eradication on high dose pentagastrin-stimulated acid secretion was also seen at the 12-month study (mean = 48.9, p < 0.02 versus entry). CONCLUSION: The findings of this study suggests that maximally stimulated acid secretion is modestly, albeit significantly, reduced following Helicobacter pylori eradication and that this effect persists.     

Elevation of serum tumor marker CA 15.3 levels as the first manifestation of metastatic breast cancer to the cavernous sinus

We report rising tumor marker levels of CA 15.3 as the presenting manifestation of metastatic breast cancer to the cavernous sinus and orbit. A 39-year-old woman with a history of breast cancer developed increasing levels of tumor marker CA15.3. Ten months later, she developed vision loss in the right eye, diplopia, and right-sided ptosis. A magnetic resonance scan of the head showed a mass involving the right cavernous sinus and superior orbital fissure. Biopsy of the lesion showed metastatic breast cancer. She was treated with surgery and radiotherapy and did well. Ophthalmologists should be aware of the significance of increasing levels of tumor markers, such as CA 15.3, in patients with a history of breast cancer and new neuroophthalmologic signs or symptoms.     

Investigation of the usefulness of CYFRA 21-1 as a tumor marker in squamous cell carcinomas of the head and neck

Compressive contact stress between the patella and the anterior femur and between the quadriceps tendon and anterior femur was measured before and after total knee arthroplasty in 5 cadaver knee specimens using a digital electronic sensor. Contact stresses were measured in the normal knee and after total knee arthroplasty with an unresurfaced patella, a dome-shaped patella, and a conforming patella. Patellofemoral contact stresses did not change significantly after total knee arthroplasty when the patella was not resurfaced, but they increased significantly after the patella was resurfaced with both the dome-shaped and the conforming components. The conforming patella had the highest contact stresses because it tilted at flexion angles greater than 90 degrees and applied load to a small area on the superior portion of the patellar component. The conforming patella markedly decreased tendofemoral contact force because the thicker superior pole of the patella tented the quadriceps tendon at flexion angles greater than 120 degrees. This further increased patellofemoral contact force in deep knee flexion.     

High bone mass as a marker for breast cancer risk

Postmenopausal women in the highest quartile for metacarpal bone mass were found to have an increased risk of developing breast cancer, after adjusting for age and other variables known to influence breast cancer risk. Although the mechanisms responsible for this relationship have not been identified, postmenopausal bone mass may serve as an indicator of cumulative estrogen exposure.