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Biomedical subjects

K L Becker

Publications and source records attributed to K L Becker.

At least 55 records · Page 3Linked to original sources
PubMed1990

Pulmonary bombesin and calcitonin in hamsters during exposure to hyperoxia and diethylnitrosamine.

Combined exposure of hamsters to 60% hyperoxia and the carcinogen diethylnitrosamine for 6 wk resulted in the development of lung tumors. This was associated with progressive loss of body weight as well as increases in the pulmonary-associated peptides, mammalian bombesin (MB) and immunoreactive calcitonin (iCT). After 3 wk of exposure, multiple bronchial epithelial hyperplastic foci were noted, along with increased lung levels of MB and iCT as well as increased serum levels of MB. At this time, immunocytochemistry revealed the presence of MB and iCT within hyperplastic pulmonary neuroendocrine (PNE) cells. In addition, the localization of MB to alveolar type II cells was noted, along with the presence of lamellar bodies and secretion granules in these cells on electron microscopy. After 6 wk of exposure, distinctive microscopic pulmonary tumorlets were seen. These tumorlets were associated with a marked increase in lung and serum MB, and to a lesser extent lung and serum iCT. At this time, MB and iCT were localized exclusively to these abnormal PNE cell sites. These results, which may have relevance in humans, suggest that endogenous peptides may be important components in the process of development of neuroendocrine cancer.

Animals↗
PubMed1989

Stimulation of hamster pulmonary neuroendocrine cells and associated peptides by repeated exposure to cigarette smoke.

Although the normal function of pulmonary neuroendocrine (PNE) cells containing bioactive peptides is poorly understood, various pulmonary diseases are associated with hyperplasia of these cells, and they also may be progenitors for small cell lung cancer in humans. In this study we have investigated the effects of subchronic cigarette smoke exposure in the hamster on the PNE cells and their peptide content. Daily exposure to standard research cigarette smoke for as long as 90 days led to progressively higher levels of serum calcitonin (iCT) as well as higher lung tissue iCT and the gastrin releasing-like peptides or mammalian bombesin (MB). Subsequent to a 30-day period during which there was no further exposure to smoke, serum levels returned to control levels, but the lung levels of both iCT and MB remained higher than control levels. Also, after the 90 days of exposure, immunocytochemistry revealed an increase in the number of iCT-containing PNE cells. This increase in the number of PNE cells correlated well with the increased iCT content of the lung tissue. We conclude that subchronic cigarette smoke exposure causes an increase in pulmonary levels of iCT and MB, which may be linked to the observed proliferative response of the PNE cells.

Animals↗
PubMed1988

Primary culture of the enteric nervous system from neonatal hamster intestine. Selection of vasoactive intestinal polypeptide-containing neurons.

The enteric nervous system is a major division of the autonomic nervous system and is responsible for the regulation of gastrointestinal function. The objective of the present study was to develop a simple and effective technique for isolating and culturing neurons of the enteric nervous system that would permit characterization of their development and regulatory peptide content. This was accomplished using a dispersed intestinal cell preparation cultured under conditions designed to support the growth and differentiation of neurons and neuroendocrine cells. Newborn hamster intestine was digested in 0.1% collagenase, mechanically dispersed, and cultured in RPMI 1640 supplemented with 2.5% serum and other additives. Phase and bright-field microscopy demonstrated neuronal cells and fibers after the second day in culture. This was confirmed by immunohistochemistry using antibodies directed against neurofilament and vasoactive intestinal polypeptide. Acetic acid extracts of the culture indicated that during the first 4 days of the culture the content of vasoactive intestinal polypeptide increased, whereas the content of substance P, mammalian bombesin, and neurotensin declined. High-performance liquid chromatography and fast protein liquid chromatography confirmed that the immunoreactive vasoactive intestinal polypeptide coeluted with synthetic and iodinated forms of the peptide. This study describes a technique for primary culture of intestinal tissue that supports the survival of enteric neurons and permits analysis of the development and synthetic and secretory characteristics of the enteric nervous system.

Animals↗
PubMed1988

Evidence for cigarette smoke-induced calcitonin secretion from lungs of man and hamster.

In hamsters, acute cigarette smoke inhalation increased serum levels of the hormone calcitonin; and, in humans, smoking of two high-nicotine content cigarettes increased serum and urine levels of this hormone. The source of this immunoreactive calcitonin (iCT) does not appear to be the thyroid gland, since previously thyroidectomized patients demonstrated a similar response. In the hamster, the increased serum iCT levels were accompanied by a decreased lung tissue iCT content and hypocalcemia. It is suggested that the source of the cigarette smoke-induced hypercalcitonemia is the lung, possibly from the iCT-containing pulmonary neuroendocrine (PNE) cells. Moreover, this response appears to be dependent on the nicotine content of the cigarettes.

Animals↗
PubMed1988

An animal model for neuroendocrine lung cancer.

Neuroendocrine lung cancer is among the most common types of lung tumor in man and demonstrates a strong etiological association with cigarette smoking. However, despite numerous efforts, this cancer type has never been induced in animals. This report describes, for the first time, the reproducible induction of pulmonary neuroendocrine cancer in a readily available hamster model. The data provide evidence that deviations from pre-existing normal pulmonary oxygen levels may be an essential factor for the induction of this malignancy. This new model should greatly facilitate studies of the pathophysiology, biochemistry and therapy of neuroendocrine cancer of the lung.

Animals↗
PubMed1986

Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c-myc proto-oncogene.

Small cell lung cancer growing in cell culture possesses biologic properties that allow classification into two categories: classic and variant. Compared with classic small cell lung cancer cell lines, variant lines have altered large cell morphology, shorter doubling times, higher cloning efficiencies in soft agarose, and very low levels of L dopa decarboxylase production and bombesin-like immunoreactivity. C-myc is amplified and expressed in some small cell lung cancer cell lines and all c-myc amplified lines studied to date display the variant phenotype. To investigate if c-myc amplification and expression is responsible for the variant phenotype, a normal human c-myc gene was transfected into a cloned classic small cell lung cancer cell line not amplified for or expressing detectable c-myc messenger RNA (mRNA). Clones were isolated with one to six copies of c-myc stably integrated into DNA that expressed c-myc mRNA. In addition, one clone with an integrated neo gene but a deleted c-myc gene was isolated and in this case c-myc was not expressed. C-myc expression in transfected clones was associated with altered large cell morphology, a shorter doubling time, and increased cloning efficiency, but no difference in L dopa decarboxylase levels and bombesin-like immunoreactivity. We conclude increased c-myc expression observed here in transfected clones correlates with some of the phenotypic properties distinguishing c-myc amplified variants from unamplified classic small cell lung cancer lines.

Animals↗
PubMed1986

Cerebrospinal fluid bombesin and calcitonin in patients with central nervous system metastases from small-cell lung cancer.

To determine whether levels of mammalian bombesin (MB) or calcitonin would be useful in detecting CNS metastases in patients with small-cell lung cancer (SCLC), we measured their concentrations in the CSF of 94 patients who underwent lumbar puncture for suspected CNS involvement. The MB concentration was significantly elevated in the 51 patients with definite CNS metastases as compared with the 30 patients without apparent CNS involvement (P less than .01). This significance was due to increased levels of MB in 18 patients with meningeal carcinomatosis. Whereas CSF MB was detectable (greater than 10 fmol/mL) in only 7% of patients without apparent CNS involvement, CSF MB was detectable in 21% with parenchymal CNS metastases and in 78% of those with meningeal carcinomatosis. Interestingly, 93% of patients having MB concentrations above 20 fmol/mL had meningeal metastases. The calcitonin concentration was significantly elevated in 42 patients with CNS metastases as compared with 27 patients without CNS involvement (P less than .01). Both the 15 patients with meningeal carcinomatosis and the 27 patients with only parenchymal metastases had significantly elevated levels of CSF calcitonin as compared with those without CNS metastases. Fifty-three percent of patients with meningeal carcinomatosis and 48% with parenchymal metastases had a CSF calcitonin level above 18 fmol/mL, whereas only 7% without apparent CNS metastases exceeded this level. Sixty-seven percent of all patients with CNS metastases had increased CSF levels of one of the two hormonal markers. Thus, in SCLC patients, an elevated CSF calcitonin strongly suggested CNS metastases and an elevated MB was very suggestive of the presence of meningeal carcinomatosis. However, only the latter observation seems of clinical importance due to the difficulties in establishing this diagnosis with current diagnostic measures.

Bombesin↗
PubMed1986

Somatostatin analog: effects on hypergastrinemia and hypercalcitoninemia.

A somatostatin analog (SMS 201-995) was used to treat symptomatic patients with a residual tumor burden of gastrinoma or medullary thyroid carcinoma and pathologic elevations of circulating marker peptides associated with these neuroendocrine tumors. Possible inhibitory effects of the analog on marker peptides, patients' symptoms, or tumor progression were studied in a dose-response protocol and during several months of self-injection of SMS 201-995. Both patients reported remarkable relief of secretory diarrhea and other symptoms, and serum gastrin was successfully suppressed by increasing doses of the analog. However, no effect was seen in reduction of hypercalcitoninemia. Morphologic imaging of residual tumor showed no progression of medullary thyroid carcinoma during treatment and, in the case of hepatic gastrinoma metastases, remarkable tumor regression was confirmed. No toxicity or glucose intolerance was experienced. Somatostatin analog shows promise for palliative management of endocrinologic symptoms due to neuroendocrine tumors, and an inhibitory effect can be measured in some but not all peptide markers. Further evidence of its negative trophic effect on tumor blood flow may suggest an antineoplastic potential, as well as palliative use of this new treatment.

Adult↗