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W G Hammond

Publications and source records attributed to W G Hammond.

At least 19 recordsLinked to original sources
PubMed1999

Lack of influence of hysterectomy on meal size and meal number in Fischer-344 rats.

Based on our previous observation that, when eating the same amount of food per 100 g b.wt., male rats gain five to seven times more weight than females who have an estrous cycle every 4 to 5 days, we questioned whether lower weight gain seen in female rats could be the result of increased energy cost in preparing endometrium for anticipated fertilization. Because the uterus modulates estrogenic effects on other hormone-dependent behaviors, for example, sexual receptivity and lordosis, we performed this study to determine if estrogen-mediated cyclical changes in food intake and feeding pattern occur after hysterectomy. Fifteen female Fischer 344 rats were randomized during the estrous phase to either hysterectomy with ovarian preservation or sham operation. A rat eater meter was used to continuously measure food intake, meal number, and meal size for two estrous cycles before and four cycles after surgery. Both groups showed the estrous phase linked cycling in meal number, meal size, and food intake. No differences existed between the two groups in these indices either before or after surgery. No differences existed between groups in rate of body weight gain after surgery, 0.95 +/- 0.13 g/day in hysterectomized and 0.77 +/- 0.1 g/day in sham-operated rats. We conclude that hysterectomy has no effect on rate of weight gain, food intake, and estrus linked cyclical feeding pattern in Fischer 344 rats.

Animals↗
PubMed1996

Bronchial carcinogenesis in syngeneic hamsters.

Endobronchial sustained release implants of carcinogen were placed in males (m) and females (f) of four varieties of syngeneic hamsters: BIOF1D; BIO87.20; BIO1.5; BIO15.16. The sequential progression of carcinogenesis that occurred was faster for 1.5m than for 1.5f (P = 0.01) and less rapid for 15.16m than for 87.20m and F1Dm (P < 0.05). Fewer invasive cancers occurred in 15.16m than in the other male varieties (P < 0.01), in 1.5m than in 87.20m (P < 0.05), and in 87.20f than in 87.20m (P < 0.05). Adenocarcinoma occurred with greater frequency in the 1.5 variety than in the F1D variety (P < 0.05). Significant variability in susceptibility, incidence, and types of invasive cancers formed exists, providing new opportunities for further study of bronchial carcinogenesis.

Animals↗
PubMed1996

Alveolar stem cells in canine bronchial carcinogenesis.

Alveolar type II cells are not present in normal epithelium of canine segmental bronchi but after carcinogen exposure they do occur in intra-epithelial lesions with all degrees of atypia and in invasive lesions with different glandular growth patterns. Immunohistochemistry for proliferation markers (PCNA; Ki-67) strongly suggest that such novel type II cells are pluripotential stem cells in canine bronchial carcinogenesis. Very likely, bronchial carcinogenesis is subject to an oncofetal mechanism of differentiation: bronchial epithelial retrodifferentiation followed by novel differentiation of alveolar tumor stem cells.

Animals↗
PubMed1996

Studies on the regulation of food intake using rat total parenteral nutrition as a model.

Total parenteral nutrition (TPN) is essential for maintaining the nutritional status of patients who are unable to eat sufficiently to meet their metabolic needs. However, TPN suppresses appetite and ultimately diminishes food intake. Theories concerning the role(s) of peripheral metabolites as signals, acting via the liver and the hypothalamus, for the metabolic control of food intake, have been put forward to explain the anorectic effect of TPN. In addition, it is postulated that changes in peripheral metabolites during TPN may be translated into changes in the levels of brain neurotransmitters known to decrease food intake. This review summarizes studies concerning the effect of TPN on food intake. These studies have involved: (1) characterizing the changes in feeding activity due to TPN; (2) investigating the involvement of the central nervous system; and (3) investigating the role of the periphery and its metabolites in the regulation of food intake during TPN. Some insight into the mechanism of action of TPN on food intake is provided.

Animals↗
PubMed1996

John M. Kinney, MD.

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Awards and Prizes↗
PubMed1995

Loss of nm23 and Alu DNA in human lung cancer propagated in nude mice.

Freshly resected human non-small cell lung cancer (NSCLC) has been successfully transplanted and propagated subcutaneously in nude mice (Cancer Letters 61 (1991) 53-60). We used this model to study the changes of the human metastasis suppressor genes, nm23-H1 and nm23-H2, through the process of propagation and metastasis of human NSCLC. Using a non-radioisotopic Southern analysis, the nm23-H1 and nm23-H2 genes were detected without evidence of deletion in the early generations of the tumor grafts. These genes, however, were absent from the tumor grafts sampled past 4 generations of propagation and from all the propagated metastases originated from the subcutaneous grafts. Further restriction analysis revealed that only mouse DNA, but no human Alu DNA, was present in the tumor specimens which lacked the human nm23 genes. Thus, there is a loss of human DNA but a gain of mouse DNA in the propagated tumors originated from the transplanted human NSCLC. The mechanisms of loss of human DNA in these propagated tumors in nude mice have yet to be delineated.

Animals↗
PubMed1995

Histogenesis of adenosquamous bronchogenic carcinoma.

In our hamster lung cancer model studies, among 463 non-small-cell lung cancers (NSCLC), there were 47 adenosquamous neoplasms. In 24 of 27 lesions with diameters of less than 3.0 mm, the adenocarcinoma and the squamous cell carcinoma components arose as separate, spatially discrete lesions, but these were separate in only 7 of 20 lesions with diameters of 30 mm or greater. Co-infiltration of the components became more frequent as tumor size increased. The usual adenosquamous variety of NSCLC is likely a collision tumor, with each component possessing separate biological characteristics. Thus, future prognostically directed studies of this variety of NSCLC must recognize that these neoplasms have two components, each of which needs to assessed.

Adenocarcinoma↗
PubMed1995

Successful xenotransplantation of human lung cancer correlates with the metastatic phenotype.

BACKGROUND: Occult micrometastases could explain deaths from stage I non-small cell lung cancer (NSCLC) after complete resections. If patients who have occult metastases could be identified, systemic therapy might be beneficial. METHODS: Non-small cell lung cancers from 81 patients in stages I, II, and III were transplanted to nude beige mice. Mean follow-up was 22.5 months (2 to 61 months). RESULTS: Twenty-one xenotransplants successfully took, and seven metastasized in the nude mice. Neither the predominant cell type nor the incidence of lymph node metastases correlated with the results of xenotransplantation. Of the 21 patients whose NSCLCs took in xenotransplantation, 13 (61.9%) have had development of metastases, and 9 (42.9%) have died of the cancer. Among the 57 patients whose NSCLCs did not take, 14 (24.6%) have had development of metastases, and 9 (15.8%) have died of their cancer. The higher incidence of metastases in association with xenotransplant take is significant (p = 0.0032). CONCLUSIONS: Patients whose NSCLCs take in xenotransplantation are at high risk for metastases. The xenotransplantation model is a step toward facilitating precise cellular biologic definition of the metastatic propensity of human NSCLC:

Animals↗
PubMed1994

In favour of an oncofoetal concept of bronchogenic carcinoma development.

Our recent studies in a heterotopic model of non-small cell lung cancer in dogs (subcutaneous bronchial autografts treated with 3-methylcholanthrene) have provided evidence that alveolar type II cells may newly arise during initial phases of bronchial carcino-genesis. In the light of these novel findings, which are in agreement with our observations in human non-small cell lung cancer, and in view of present insights into embryonic lung differentiation, we discuss evidence that favours a new, oncofoetal concept of bronchogenic carcinoma development. According to this concept, the primary cells of origin for these tumors are undifferentiated primordial-like cells that derive from bronchial epithelial cells present in major bronchi or their divisions by retrodifferentiation. Such primordial-like cells of origin undergo novel differentiation into the potential (alveolar, bronchial or primordial) tumor stem cells, which occupy the dividing cellular layers of the (pre)neoplastic lesions and constitute the actively dividing and invading part of the neoplasm. Examples of tumors that may originate from alveolar tumor stem cells are carcinomas of the bronchiolo-alveolar, papillary, acinar, and adenoid-cystic types. Squamous cell carcinomas could possibly belong to this group as well, but much more evidence is required to reach conclusions regarding this type of cancer. We suggest that epithelial retrodifferentiation followed by novel differentiation (oncofoetal mechanism) is fundamental in bronchial carcinogenesis.

Animals↗
PubMed1993

A step section method for full histopathological assessment of carcinogen-affected target tissue during respiratory carcinogenesis.

Studies of carcinogenesis that are not limited to overt neoplasms but also involve evaluations of preneoplastic stages require histopathological assessment of the entire carcinogen-affected tissue so that the true nature and sequence of the progressive process can be determined. The customary serial sectioning approach achieves this goal, but at an inordinate logistic cost. In studies of hamster bronchial carcinogenesis, a step section method was compared to a quasi-random approach and to the customary serial section method. The step section method achieved the same diagnostic completeness as serial sectioning, but at a two orders of magnitude reduction in costs.

Animals↗
PubMed1993

Hamster bronchial carcinogenesis induced by carcinogen-containing sustained release implants placed endobronchially: a clinically relevant model.

For several widely appreciated reasons, the Syrian hamster has been the most frequently used experimental animal in investigations of conducting airway carcinogenesis. To develop a model where bronchogenic cancer arises focally at a predetermined site, we used the Laskin-Kuschner self-retaining intrabronchial pellet principle, employing a carcinogen-containing silastic polymer sustained release implant (SRI). The SRI is placed in the right lower lobe bronchus via tracheostomy; when modified, the SRI can be removed without loss of the animal. Special preparation of the SRI implant site after fixation but prior to paraffin embedding allows for full histopathological examination of the carcinogen-affected target tissue. Logistic regression analysis of histological findings provides valid quantitative inter-regimen comparisons of histomorphic classifications suitable for determining modulation of carcinogenesis by external influences. Using this model, we demonstrated that the sequential progression of carcinogenesis (SPC) in hamster bronchus is similar to that which occurs in humans and in dogs, including both the ploidy increases that are progressive during the SPC, and the histological patterns of the induced cancers. We have shown genetic variation in susceptibility to carcinogenesis among inbred hamster strains, and have assessed effects of Bacillus Calmette-Guerin (BCG) immunostimulation on the SPC. Time/dose response studies were performed, as were comparisons between four polycyclic aromatic hydrocarbon carcinogens. Systemic administration of 5-azacytidine (AZC) soon after SRI placement was found to inhibit the SPC, to alter the ploidy changes during the SPC and in the eventual cancers, and to affect the degree of differentiation of the cancers. Studies using removable SRIs have assessed the duration of carcinogen exposure required to induce a neoplastic transformation that proceeds to cancer without further carcinogen exposure. Serial syngeneic transplantation of cancers arising in inbred animals has shown that the degree of tumor differentiation is affected by the extent of host immunocompetence, and has also led to development of models for study of the processes of metastasis.

Animals↗
PubMed1993

Regression of bronchial epithelial cancer in hamsters.

For bronchogenic carcinoma, if and when the sequential process of carcinogenesis is reversible is fundamental to chemoprevention research. In our hamster model, focally originating non-small cell lung carcinoma (NSCLC) develops via a reproducible sequential process of carcinogenesis by 180 days after endobronchial sustained-release implants (SRIs) of 10% benzo(a)pyrene. In this study, 114 hamsters received removable 10% benzo(a)pyrene SRIs. Short-term controls were sacrificed in 3 groups at 50, 65, and 80 days after SRI placement. Three experimental groups had SRIs removed at 50, 65, and 80 days after placement, and sacrifice was delayed until 100 to 180 days later. Long-term controls retained SRIs until sacrifice at 180 or 240 days after SRI placement. All long-term controls had NSCLC. Preneoplastic change was more common in 50- and 65-day controls, as compared with hamsters with equal duration of SRI exposure whose sacrifice was delayed until 100 to 180 days after SRI removal (p < 0.05). The 56% incidence of early NSCLC in hamsters sacrificed after 80 days of SRI exposure decreased to 5% in hamsters that had delayed sacrifice after SRI removal after 80 days of exposure. At the 10% benzo(a)pyrene dose used, hamster bronchial epithelium requires more than 80 days of continuous exposure to become irreversibly committed to NSCLC uniformly. Microinvasive NSCLC in hamsters often regresses, and it is not necessarily a precursor of overt invasive cancer. The removable SRI model provides new opportunities to evaluate chemoprevention of NSCLC and the related molecular-genetic control mechanisms.

Animals↗
PubMed1993

Expression of alveolar type II cell markers in acinar adenocarcinomas and adenoid cystic carcinomas arising from segmental bronchi. A study in a heterotopic bronchogenic carcinoma model in dogs.

The type II alveolar epithelial cell is one of two pluripotential stem cell phenotypes in normal mammalian lung morphogenesis; cells manifesting this phenotype have been found to constitute bronchioloalveolar regions of canine adenocarcinomas. We now studied type II cell expression in canine acinar adenocarcinomas and adenoid cystic (bronchial gland) carcinomas, using the same bronchogenic carcinoma model (subcutaneous bronchial autografts treated with 3-methylcholanthrene). Distinctive features of type II cells are the approximately cuboid cell shape, large and roundish nucleus, immunofluorescent staining of the cytoplasm for the surfactant protein SP-A, and presence of multilamellar bodies or their precursory forms. Cells with these type II cell characteristics were found in the basal epithelial layer of all tumor lesions and in upper layers as far as the lumen, singly or in clusters; they were also found in early invasive carcinomatous lesions but not in bronchial glands or bronchial epithelium before carcinogen exposure. Immunoblots of tumor homogenates showed reactive proteins within size classes of SP-A (28 to 36 kd) or its dimeric form (56 to 72 kd). These findings and those previously reported are consistent with the concept that chemical carcinogenesis in the adult bronchial epithelium may lead to type II cell carcinomas of varying glandular (acinar, adenoidcystic or bronchioloalveolar) growth patterns.

Animals↗
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↗