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Biomedical subjects

W G Hammond

Publications and source records attributed to W G Hammond.

12 recordsLinked to original sources
PubMed1992

Bronchial and pulmonary carcinogenesis at focal sites in dogs and hamsters.

Models of the sequential process of lung carcinomas have been developed in dogs and hamsters. The bronchial mucosa, or the pulmonary parenchyma, was exposed at selected focal sites to polycyclic aromatic hydrocarbons [most often benzo(a)pyrene or methylcholanthrene]. In hamsters, sustained release implants that contained carcinogen were implanted into the right lower lobe bronchus. In dogs, for orthotopic carcinogenesis the carcinogens were repeatedly injected into the bronchial submucosa or topically applied to the bronchus; sustained release implants were implanted into the pulmonary parenchyma. Heterotopic focal canine bronchial carcinogenesis was accomplished by exposing s.c. bronchial autografts (8-12/dog) to methylcholanthrene. In both species a predictable, reproducible, preneoplastic continuum that leads to bronchial squamous cell carcinoma that metastasizes has been characterized; serial measurements of total cellular DNA showed that ploidy increased in proportion to the stage of preneoplasia. In both species there were adenocarcinomas, including bronchiolar (bronchioloalveolar) carcinomas and other varieties of non-small cell cancers. Different susceptibility to carcinogenesis has been demonstrated among different inbred strains of hamsters; 58% of cancers were adenocarcinomas in one strain. From these models, specimens that are not readily available from humans can be obtained for the study of cellular events during lung carcinogenesis. In parallel with studies in humans, these animal models can be used to evaluate methods of possible chemoprevention and early detection.

Animals↗
PubMed1991

Metastases from fresh human non-small cell lung cancers propagated in nude mice.

Specimens from 69 freshly resected human non-small cell lung cancers (NSCLC) were transplanted into nude mice. Twelve mice died before the transplants were evaluable. There were 4 takes of 12 evaluable transplants into untreated athymic nude mice and 24 takes of 45 evaluable transplants into nude mice with decreased natural killer (NK) cell activity. Fourteen tumor lines were propagated into 2 or more successive transplant generations. Distant metastases occurred from the mid-dorsal transplant site in 8 of 81 (9.88%) recipients of 4 of those tumor lines, after 3-9 consecutive tumor growth cycles. Xenotransplantation of freshly resected human NSCLC provides a model with potential for serial assessment of cellular changes related to metastatic capability.

Adenocarcinoma↗
PubMed1991

Lung cancer model for study of the metastatic process.

In our hamster model of focal, chemically induced nonsmall cell lung cancer (NSCLC), we studied metastases in autochthonous hamster hosts (n = 300) and in syngeneic hamster and nude mice recipients (n = 230) of serial tumor transplants. Metastases in autochthonous hosts and transplant recipients occurred in regional lymph nodes, liver, and adrenals. In autochthonous host hamsters no metastases were noted from microinvasive (n = 112) or visible cancer less than 3.0 mm in diameter (n = 66); the incidence of metastasis was 8.2% (4/49) from 3- to 10-mm cancers and 22% (16/73) from cancers 10 mm in diameter or larger (p less than 0.05). Serial transplants were used to evaluate the metastatic propensity of 20 primary and six metastatic NSCLCs. Six primary NSCLCs that metastasized in the autochthonous host and six metastatic NSCLCs all metastasized promptly in recipients. This expression of metastatic potential was significantly different (p less than 0.05) from 14 primary cancers without autochthonous host metastases. Eight of the 14 caused no metastases in recipients, even after 5 to 11 tumor growth cycles; metastases occurred from the other six primary NSCLC after 3 to 12 tumor growth cycles in transplant recipients. Primary hamster NSCLCs metastasize in the autochthonous host with a frequency and a distribution pattern similar to human NSCLCs. A new model to study serially the cellular changes that govern the process of metastasis in NSCLC has been developed.

Animals↗
PubMed1991

Variable regression of experimental bronchial preneoplasia during carcinogenesis.

It has been thought that squamous severe atypical metaplasia of the bronchus is reliably precancerous. The canine subcutaneous bronchial autograft model for studying the progression of epidermoid carcinogenesis (normal----regular squamous metaplasia----mild, moderate, and severe atypical metaplasia----squamous cell carcinoma) provides evidence that severe atypical metaplasia of the bronchial epithelium is reversible. Among 148 subcutaneous bronchial autografts that had serial sampling of the epithelium and exposure to implants of methylcholanthrene, severe atypical metaplasia was noted in 28 that received only a single implant. During the total carcinogen exposure (median 24.5 months), 9 of 28 (32%) developed squamous cell cancer, and 19 of 28 (68%) regressed toward normal. Severe atypical metaplasia was noted in 34 subcutaneous bronchial autografts that received two or more carcinogen implants: epidermoid cancer developed in 26 of 34 (76.5%), and regression toward or to normal occurred in 8 of 34 (23.5%). Severe atypical metaplasia was not detected in 53 subcutaneous bronchial autografts: 19 that received only a single implant and 34 that received two or more implants. Progression and regression occurred among these subcutaneous bronchial autografts in proportions similar to those found in subcutaneous bronchial autografts wherein severe atypical metaplasia was seen. Among 33 subcutaneous bronchial autografts initially studied after 6 months of exposure to carcinogen, progression to severe atypical metaplasia was seen 3 months later in 19 of 33 that had additional exposure; in the same interval regression of epithelial abnormalities occurred in 14 of 33 subcutaneous bronchial autografts that had no additional exposure (p less than 0.05). We have presented evidence that severe atypical metaplasia includes at least three cell populations: one committed to cancer without further stimulus, one that regresses despite further carcinogen exposure, and one that requires additional carcinogen to progress to cancer. At least in this model, severe atypical metaplasia is not inexorably precancerous. The subcutaneous bronchial autograft model is suitable for seeking biologic indicators of irreversibility.

Animals↗
PubMed1990

Bronchiolo-alveolar regions in adenocarcinoma arising from canine segmental bronchus.

Adenocarcinomas induced in canine bronchial segments placed subcutaneously have bronchiolo-alveolar regions. Immunocytochemistry and routine staining of adjacent sections strongly suggests that the lining of these regions consists of type II cells. These regions may thus represent true prospective alveolar regions, as also seen in embryonic lungs. This first observation of bronchoalveolar cancer arising from a major bronchus indicates that the carcinogen-induced neoplastic progression in bronchial epithelium may lead to type II cell differentiation and type II cell tumor development. The preservation of cell properties in serial nude mouse transplants suggests that it is a stable type II cell population.

Adenocarcinoma↗
PubMed1990

Effects of 5-azacytidine in Syrian golden hamsters: toxicity, tumorigenicity, and differential modulation of bronchial carcinogenesis.

5-Azacytidine (AZC) was studied in a lung cancer model in outbred and syngeneic (F1D) hamsters wherein benzol[a]pyrene (BP) from sustained release implants (SRI) induces preneoplastic mucosal changes which progress to bronchogenic cancer. In pilot studies to evaluate AZC toxicity, a dose schedule of 5 mg/kg biweekly was found suitable and was then used for long-term administration in all subsequent studies. Three groups of outbred hamsters were studied: BP SRi alone (n = 60), BP SRI + AZC (n = 60), and AZC alone (n = 54). AZC treatment was begun 3-5 days after SRI placement. Sixty-one days after the start of the experiment, seven or eight hamsters were sacrificed from each group. Later sacrifices were at 3-week intervals in groups receiving BP SRI and at 6-week intervals in the AZC only group. Four groups of F1D syngeneic hamsters were studied: BP SRI alone (n = 50); BP + AZC starting 3-5 days after SRI placement and continuing until death (n = 52); BP + AZC from 3 to 5 days until 75 days after SRI placement (n = 49); BP + AZC starting 80 days after SRI placement and continuing until death (n = 52). Hamsters (n = 9-14) from each group were sacrificed at 120, 150, 180, and 220 days after SRI implantation. AZC alone was not carcinogenic under these conditions. Both outbred and F1D hamsters treated with early or continuous AZC had slower rates of neoplastic change from BP SRI than did animals receiving BP SRIs alone or BP + late AZC. The incidence of epidermoid cancer were the same for all regimens, but the tumors in those receiving AZC early in carcinogenesis were smaller than in those receiving late or no AZC. The incidences of nonepidermoid cancer were lower in those receiving AZC during early carcinogenesis, and larger tumors were noted in the absence of AZC. Thus, within the study period in this unique hamster lung cancer model, AZC given early in carcinogenesis inhibited only the later (promotional) phase of BP epidermoid carcinogenesis, but inhibited all phases of nonsquamous cancer development induced by BP. This differential modulation of bronchial carcinogenesis, which occurs from AZC given during preneoplastic stages, may prove useful for delineating molecular mechanisms underlying specific phenotypic types of bronchogenic cancers.

Animals↗
PubMed1990

Automated computerized rat eater meter: description and application.

A real-time Automated Computerized Rat Eater Meter was developed by modifying commercially available metabolic cages. Food access via a feeding tunnel was monitored by photocells. Food consumption was measured by an electronic scale. The signals thus generated were processed by a computer. This allowed us to continuously measure the spontaneous feeding behavior of free-feeding nondeprived Fischer rats for a sum total of 35 study days. Based on our data, we defined a meal as an episode of food consumption preceded and followed by at least 5 minutes of no feeding. Fischer rats showed periodic nychthemeral eating behavior. Food consumption, number of meals, meal sniffs, intermeal sniffs, and, consequently, eating activity were greater during the dark cycle than the light cycle. Meal duration, meal size, and thus food consumption rates remained constant throughout both cycles. Our modification of commercially available metabolic cages provides unique data for continuously monitoring rat feeding patterns over prolonged periods of time.

Animals↗
PubMed1990

Nutritional support in surgical practice: Part I.

Critical evaluation of the therapeutic benefit gained from provision of nutritional support requires knowledge regarding the nutritional status of those to whom it was given. The apparent effect of giving parenteral nutrition or enteral nutrition depends not only on how much and how well it is given, but also on how depleted the recipient is. Thus, nutritional assessment requires close examination before proceeding to assess the efficacy and potential benefits of the remedial measures of parenteral nutrition or enteral nutrition. Although preoperative malnutrition is associated with a poor operative outcome, there appears to be no consensus as to whether perioperative nutritional support can reduce postoperative complications to the level occurring in well-nourished patients undergoing similar procedures. This is partly because reports evaluating the effect of perioperative nutritional support on postoperative outcome vary widely as to numbers of patients studied, primary diagnoses, and the duration and quality of perioperative nutritional support. In Part I, these issues are explored in patients who are undergoing operations for cancer, trauma, or burns. Enteral nutrition appears to be as effective as parenteral nutrition in improving operative outcome, as compared with ad libitum oral nutrition. Postoperative enteral nutrition and parenteral nutrition are equally effective in reducing postoperative complications.

Enteral Nutrition↗
PubMed1990

Nutritional support in surgical practice: Part II.

On admission, a group of high-risk patients who are potential candidates for surgery can be identified, in whom prompt initiation of preoperative enteral or parenteral nutrition may reduce postoperative morbidity and mortality irrespective of the nutritional status. Among these are patients with inflammatory bowel disease, gastrointestinal fistulas, and pancreatitis. Substantial nutritional support has little or no direct effect upon the pathogenesis of the disease, but the discontinuance of oral intake may well have a beneficial effect on the basic disease process. Thus, the provision of enteral or parenteral nutrition gives the patient an optimal opportunity to marshal host defenses in support of healing. In organ system failures, e.g., acute renal failure, liver failure, and pulmonary failure, appropriate nutritional support may assist the patient in coping with the abnormal intermediary metabolism resulting from such failure until satisfactory organ system function returns. From this review, it seems reasonably clear that the initially malnourished patient is less able to successfully withstand the adverse effects of vigorous therapy and/or severe illness than is the well-nourished individual. Hence, correction of malnutrition, either before initiating therapy or concomitant with the treatment, is very likely to be beneficial.

Acute Disease↗
PubMed1990

Quantitative DNA alterations during 5-azacytidine-induced differential modulation of benzo(a)pyrene carcinogenesis in hamster bronchi.

Sustained release implants (SRI) containing 10% benzo(a)pyrene (BP) were placed endobronchially into outbred and syngeneic (F1D) hamsters. Randomly selected OB and F1D hamsters also received 5-azacytidine (AZC), 5 mg/kg i.p., twice weekly until death (AZC-CONT); two more groups of F1D hamsters were given the same AZC dose either for the first 75 days of SRI implantation (AZC-EARLY) or from 80 days after SRI placement until death (AZC-LATE). OB Hamsters were sacrificed at regular intervals from 62 to 189 days of SRI exposure. F1D Hamsters were sacrificed in groups after 120, 150, 180, and 220 days of SRI exposure. The bronchial mucosa at the SRI site was examined cytologically and histologically, as were the tumors that developed. Mean quantitative total cellular DNA values (QDNA) were measured by image analysis. For both varieties of hamster given AZC, QDNA values were higher in early carcinogenesis (CG) and lower in the late stage of CG than in hamsters that did not get AZC (P less than 0.001). QDNA values were lower in epidermoid than in non-epidermoid cancers (P less than 0.001); for both types of cancer, QDNA was lower in AZC-treated hamsters (P less than 0.01). Cancers induced under the influence of AZC included more epidermoid cancers (P less than 0.01) and were of a higher degree of differentiation (P less than 0.01) than those induced by BP alone, especially when AZC was given early in CG. There was no consistent relationship between QDNA and degree of differentiation in tumors. These differential effects of AZC given early during CG suggest that 1) for epidermoid bronchial CG, some of the molecular alterations involved in hyperploidy and in differentiation occur early in the sequential progression of carcinogenesis; and 2) for both epidermoid and non-epidermoid bronchial CG, the necessary changes must occur in a fixed sequence instead of as random events, until all needed changes have occurred.

Animals↗
PubMedDate not supplied

Metastatic behaviour of canine lung carcinoma in autochthonous and xenotransplant hosts.

Specimens from 24 chemically induced canine non-small cell lung cancers (NSCLC) were xenotransplanted into nude mice. Twenty-one tumour lines were established in serial transplantation; four were from NSCLC that arose from orthotopically induced NSCLC in four dogs, and 17 were from NSCLC that arose heterotopically in 15 subcutaneous bronchial autografts (SBA) in seven dogs. Distant metastases developed in recipients of two orthotopic NSCLC after three and eight consecutive tumour growth cycles; no metastases have occurred after three and six growth cycles of two other orthotopic tumour lines. Recipients of eight heterotopic tumour lines developed metastases after 3-9 consecutive tumour growth cycles, while no metastases have occurred after 4-11 growth cycles in recipients of nine other heterotopic tumour lines. In three instances, both metastasizing and non-metastasizing tumour lines resulted from NSCLC that arose in different SBAs in the same dog. These findings indicate that, in the canine SBA bronchogenic cancer model as expanded by tumour xenotransplantation, those molecular events involved in both the initiation and the full progression of a single cancer may be investigated serially and concomitantly.

Animals↗