Evaluation of the 3dMDface system as a tool for soft tissue analysis.

OBJECTIVES: To evaluate the accuracy of three-dimensional stereophotogrammetry by comparing values obtained from direct anthropometry and the 3dMDface system. To achieve a more comprehensive evaluation of the reliability of 3dMD, both linear and surface measurements were examined. SETTING AND SAMPLE POPULATION: UCLA Section of Orthodontics. Mannequin head as model for anthropometric measurements. MATERIAL AND METHODS: Image acquisition and analysis were carried out on a mannequin head using 16 anthropometric landmarks and 21 measured parameters for linear and surface distances. 3D images using 3dMDface system were made at 0, 1 and 24 hours; 1, 2, 3 and 4 weeks. Error magnitude statistics used include mean absolute difference, standard deviation of error, relative error magnitude and root mean square error. Intra-observer agreement for all measurements was attained. RESULTS: Overall mean errors were lower than 1.00 mm for both linear and surface parameter measurements, except in 5 of the 21 measurements. The three longest parameter distances showed increased variation compared to shorter distances. No systematic errors were observed for all performed paired t tests (P<.05). Agreement values between two observers ranged from 0.91 to 0.99. CONCLUSIONS: Measurements on a mannequin confirmed the accuracy of all landmarks and parameters analysed in this study using the 3dMDface system. Results indicated that 3dMDface system is an accurate tool for linear and surface measurements, with potentially broad-reaching applications in orthodontics, surgical treatment planning and treatment evaluation.

Whole stimulated salivary flow: correlation with the pathology of inflammation and damage in minor salivary gland biopsy specimens from patients with primary Sjögren's syndrome but not patients with sicca.

OBJECTIVE: To determine which measure of the salivary flow rate, stimulated or unstimulated, is most strongly associated with pathologic changes in minor salivary gland (MSG) biopsy specimens, and to explore the correlation of salivary flow with oral surface damage, disease duration, and symptom severity in patients with primary Sjögren's syndrome (SS). METHODS: In all patients (n = 32), a biopsy of the MSG was performed, and stimulated salivary flow was assessed. Beginning in 2002, unstimulated salivary flow was also assessed. Scores for the severity of symptoms, according to the decayed/missing/filled teeth (DMF) index, were recorded. Associations between measures of salivary flow and covariates characterizing pathology were examined. RESULTS: A definite association between stimulated salivary flow and the MSG focus score, the grade of MSG fibrosis, the duration of dry mouth symptoms, and the DMF score was observed. In contrast, unstimulated salivary flow was not associated with fibrosis, atrophy, the DMF score, or the duration of dry mouth symptoms. In patients with primary SS, the DMF score was associated with pathologic changes in the MSG. Among patients with sicca, 57.9% had an abnormal unstimulated salivary flow rate (versus 82.4% of patients with primary SS), and 15.2% had an abnormal stimulated salivary flow rate (versus 61.8% of patients with primary SS). Among patients with sicca, neither stimulated salivary flow nor unstimulated salivary flow was associated with the degree of fibrosis or atrophy or with the DMF score. CONCLUSION: Compared with unstimulated salivary flow, stimulated salivary flow appeared to be a better measure of inflammation (according to the focus score) and fibrosis. In patients with sicca, the unstimulated salivary flow rate appeared to be abnormal more commonly compared with the stimulated salivary flow rate. In the future, stimulated salivary flow may serve as a noninvasive surrogate biomarker of inflammation and fibrosis as well as a measure of response to treatment in patients with primary SS.

Seronegative naturally acquired West Nile virus encephalitis in a renal and pancreas transplant recipient.

West Nile virus (WNV), a single-stranded RNA flavivirus, has spread across the United States since arriving in 1999. While asymptomatic or self-limited in a majority of patients, WNV can cause a severe neuroinvasive disease, which occurs more often in transplant recipients with chronic immunosuppression. Diagnosis of acute WNV infection usually relies on serologic identification of immunoglobulin M (IgM) specific for the virus. We report a fatal case of naturally acquired WNV encephalitis in a renal and pancreas transplant recipient who was seronegative for WNV-specific IgM but had detectable WNV RNA by nucleic acid amplification testing (NAAT) several weeks after the onset of symptoms. This case demonstrates the importance of using both serologic assays and NAAT for WNV in transplant recipients with the clinical suspicion of encephalitis.

Sialoblastoma in adults: distinction from adenoid cystic carcinoma.

Essentially, sialoblastoma is a disease of infancy with the oldest case presenting at 4 years of age. About one third of pediatric sialoblastoma cases will have a cribriform growth pattern. No adult cases have been reported with a specific diagnosis of sialoblastoma. If even focal cribriforming were present, such cases have undoubtedly been diagnosed as adenoid cystic carcinoma. Such was the circumstance in the 3 adult tumors presented in this report. Each case, however, has the primitive histopathology with discrete nests of basaloid tumor cells, associated bilayered ductal structures and the fibromyxoid stroma characteristic for sialoblastoma with its resemblance to fetal salivary gland or salivary gland with arrested development. One key example has 28-year follow-up. Sialoblastoma, whether in a child or adult with or without a cribriform growth pattern, appears to have a more favorable prognosis than adenoid cystic carcinoma. Aspects of the histological differential diagnosis of these 2 tumors are discussed.

The effect of funding cuts on the utilization of an oral pathology diagnostic service.

AIM: To examine what impact the loss of funding had on the utilization of the oral pathology service. METHODOLOGY: Biopsy records were retrieved and examined in the two year period before and after the elimination of the subsidies in 2003. RESULTS: After the loss of funding, there was a 31% decrease in the number of specimens submitted from practitioners in private practice, with the greatest drop noted in submissions from endodontists. CONCLUSION: Despite the immediate decrease in the number of biopsies submitted after the introduction of fee-for-service, the number of specimens being submitted appears to be on the rise again, as practitioners appear to recognize the value of a specialized oral pathology diagnostic service.

Clinical, neuropathological and genotypic variability in SNCA A53T familial Parkinson's disease. Variability in familial Parkinson's disease.

Individuals with familial Parkinson's disease (PD) due to a monogenic defect can show considerable clinical and neuropathological variability. To identify factors underlying this variability, histopathological analysis was performed in two clinically different A53T alpha-synuclein heterozygotes from Family H, a multigenerational alpha-synuclein A53T kindred. To determine whether additional genetic factors could contribute to phenotypic variability, Family H and another multigenerational A53T kindred were analyzed for parkin polymorphisms. We identified a previously described variant in parkin exon 4 associated with increased PD risk (S167N). The two A53T heterozygotes had markedly different neuropathology and different parkin genotypes: A N167 homozygote had early onset rapidly progressive disease, early dementia, myoclonus and sleep disorder, while a S167 homozygote had late onset, slowly progressive disease and late dementia. Both had brainstem, cortical, and intraneuritic Lewy bodies (LB). The N167 individual had widespread cortical neurofibrillary degeneration, while the S167 individual had only medial temporal lobe neurofibrillary degeneration. The N167 individual had severe neuronal loss in CA2 associated with Lewy neurites (LN), while the S167 individual had severe neuronal loss in CA1 associated with TDP-43 immunoreactive neuronal inclusions. These findings implicate TDP-43 in the pathology of familial PD and suggest that parkin may act as a modifier of the A53T alpha-synuclein phenotype of familial PD. Furthermore, they suggest a mechanism by which a rare genetic variant that is associated with a minor increase of PD risk in the heterozygous state may, in the homozygous state, exacerbate a disease phenotype associated with a highly penetrant dominant allele.

Agricultural pesticide use and risk of glioma in Nebraska, United States.

BACKGROUND: To evaluate the risk of the adult glioma associated with farming and agricultural pesticide use, the authors conducted a population based case control study in eastern Nebraska. METHODS: Telephone interviews were conducted with men and women diagnosed with gliomas (n = 251) between 1988 and 1993 and controls (n = 498) randomly selected from the same geographical area. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) for farming and for use of individual and chemical classes of insecticides and herbicides, including pesticides classified as nitrosatable (able to form N-nitroso compounds upon reaction with nitrite). Non-farmers were used as the reference category for all analyses. RESULTS: Among men, ever living or working on a farm and duration of farming were associated with significantly increased risks of glioma (> or =55 years on a farm OR = 3.9, 95% CI 1.8 to 8.6); however, positive findings were limited to proxy respondents. Among women, there were no positive associations with farming activities among self or proxy respondents. Specific pesticide families and individual pesticides were associated with significantly increased risks among male farmers; however, most of the positive associations were limited to proxy respondents. For two herbicides and three insecticides, use was positively associated with risk among both self and proxy respondents. Based on a small number of exposed cases, ORs were significantly increased for the herbicides metribuzin (OR = 3.4, 95% CI 1.2 to 9.7) and paraquat (OR = 11.1, 95% CI 1.2 to 101), and for the insecticides bufencarb (OR = 18.9, 95% CI 1.9 to 187), chlorpyrifos (OR = 22.6, 95% CI 2.7 to 191), and coumaphos (OR = 5.9, 95% CI 1.1 to 32). CONCLUSION: The authors found significant associations between some specific agricultural pesticide exposures and the risk of glioma among male farmers but not among female farmers in Nebraska; however, most of the positive associations were limited to proxy respondents. These findings warrant further evaluation in prospective cohort studies where issues of recall bias are not a concern.

Autosomal dominant parkinsonism associated with variable synuclein and tau pathology.

Since the original 1995 report of a parkinsonian kindred, four individuals have been affected (mean age at onset, 65 years). All four had cardinal signs of Parkinson disease (PD) and good response to levodopa. Four autopsies showed neuronal loss and gliosis in the substantia nigra. Lewy bodies (LB) limited to brainstem nuclei were detected in one case, diffuse LB in the second, neurofibrillary tangles (NFT) without LB in the third, and neither NFT nor LB in the fourth. Genetic studies suggested linkage to the PARK8 locus on chromosome 12.

Neuropathology of two members of a German-American kindred (Family C) with late onset parkinsonism.

We present genealogical and longitudinal clinical observations and autopsy findings of a previously reported kindred, Family C (German-American), with late-onset autosomal dominant parkinsonism with evidence for linkage on chromosome 2p13. The clinical phenotype includes the cardinal features of idiopathic Parkinson's disease. In addition, postural tremor and dementia are detected in some individuals. Two members of the kindred, one affected and one unaffected have recently come to autopsy. The unaffected family member was an 82-year-old woman whose brain showed only mild age-related pathology and no evidence of subclinical Lewy body disease. In contrast, the affected family member was an 83-year-old man whose brain had neuronal loss, gliosis and Lewy bodies in the substantia nigra and other monoaminergic brain stem nuclei, as well as the basal forebrain and amygdala. Lewy bodies and Lewy neurites had a distribution typical of cases of idiopathic Parkinson's disease. Thus, the clinical and pathological findings in this family with autosomal dominant parkinsonism are similar to those of sporadic Parkinson's disease.

Diet-gene interactions in estrogen-induced mammary carcinogenesis in the ACI rat.

It is well accepted that hormonal, dietary and genetic factors each influence breast cancer risk. However, the underlying mechanisms and the extent to which these factors interact are largely unknown. We have demonstrated that the female ACI rat exhibits a unique genetically conferred propensity to develop mammary cancers when treated with physiological levels of 17beta-estradiol (E2). More recently, we have mapped to rat chromosome 5 a strong genetic modifier of susceptibility to E2-induced mammary cancers, termed estrogen-induced mammary cancer 1 (Emca1), and have identified potential Emca1 candidate genes. Because estrogens have been inextricably linked to the genesis of breast cancer in humans, the ACI rat model has the potential to reveal novel physiologically relevant insights into how the contributory actions of E2 are modified by specific dietary factors. In the present study, we have examined the ability of a 40% restriction of dietary energy consumption to inhibit E2-induced mammary carcinogenesis. The hypothesis tested was that energy restriction will inhibit mammary carcinogenesis even when circulating E2 remains elevated through administration of exogenous hormone. The data presented herein strongly suggest that energy restriction inhibits E2-induced mammary carcinogenesis in the ACI rat at least partly by retarding progression of atypical hyperplastic foci to carcinoma.

Susceptibility to estrogen-induced mammary cancer segregates as an incompletely dominant phenotype in reciprocal crosses between the ACI and Copenhagen rat strains.

Estrogens have been inextricably linked to the etiology of breast cancer. We have demonstrated that the female ACI rat exhibits a unique propensity to develop mammary cancers when treated continuously with physiological levels of 17 beta-estradiol (E2). The E2-induced mammary cancers are estrogen dependent and exhibit genomic instability. In contrast, the genetically related Copenhagen (COP) rat strain is relatively resistant to E2-induced mammary cancers. In this study we evaluated susceptibility to E2-induced mammary cancers in first filial (F(1)), second filial (F(2)), and backcross (BC) progeny generated from reciprocal intercrosses between the ACI and COP strains. F(1) progeny resembled the parental ACI strain with respect to incidence of E2-induced mammary cancers. However, latency was significantly prolonged in the F(1) populations. These data indicate that susceptibility behaves as an incompletely dominant phenotype in these crosses. Analysis of phenotypes exhibited by the F(1), F(2), and BC populations suggests that mammary cancer susceptibility is modified by one or two genetic loci in the reciprocal intercrosses between the ACI and COP strains. Susceptibility to E2-induced mammary cancers did not correlate with E2-induced pituitary growth in the genetically diverse F(2) and BC populations, suggesting that the genetic bases for susceptibility to E2-induced mammary cancers differ from those for E2-induced lactotroph hyperplasia.

Familial adenomatous polyposis and extracolonic cancer.

Our purpose is to focus attention on the cancer family history, coupled with an understanding of the natural history and extracolonic tumor spectrum of familial adenomatous polyposis (FAP), through a family study. This family report provides an example of how colorectal cancer (CRC) can be prevented by knowledgeable gastroenterologists and colorectal surgeons who educate and compassionately counsel members of high-risk families so that their compliance with diagnostic screening and, ultimately, with protection through prophylactic colectomy, is achieved. A working pedigree of this extended family was constructed through interviews with the proband, followed by questionnaires sent to all primary and secondary relatives. Appropriately signed permission forms enabled us to secure pertinent medical and pathology records in order to ensure accuracy of historical information. Integral extracolonic tumors included medulloblastoma, papillary thyroid carcinoma, hepatoblastoma, and desmoid tumors. We conclude that, due in part to improved longevity as a result of being spared CRC, several family members have developed certain FAP integral extracolonic cancers.

Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase.

Acetylcholinesterase (AChE; EC 3.1.1.7) is the primary terminator of nerve impulse transmission at cholinergic synapses and is believed to play an important role in neural development. Targeted deletion of four exons of the ACHE gene reduced AChE activity by half in heterozygous mutant mice and totally eliminated AChE activity in nullizygous animals. Butyrylcholinesterase (EC 3.1.1.8) activity was normal in AChE -/- mice. Although nullizygous mice were born alive and lived up to 21 days, physical development was delayed. The neuromuscular junction of 12-day-old nullizygous animals appeared normal in structure. Nullizygous mice were highly sensitive to the toxic effects of the organophosphate diisopropylfluorophosphate and to the butyrylcholinesterase-specific inhibitor bambuterol. These findings indicate that butyrylcholinesterase and possibly other enzymes are capable of compensating for some functions of AChE and that the inhibition of targets other than AChE by organophosphorus agents results in death.

Rat strain-specific actions of 17beta-estradiol in the mammary gland: correlation between estrogen-induced lobuloalveolar hyperplasia and susceptibility to estrogen-induced mammary cancers.

The genetically related ACI and Copenhagen (COP) rat strains display diametrically opposed susceptibilities to mammary cancer development when treated chronically with 17beta-estradiol (E2). Here, we compare the actions of E2 on cell proliferation and lobuloalveolar development in the mammary glands of female ACI and COP rats. After 12 wk of E2 treatment, the mammary glands of ACI rats exhibited a significantly greater proliferative response to E2, compared with COP rats, as evidenced by quantification of S phase fraction and development of lobuloalveolar hyperplasia. Focal regions of atypical epithelial hyperplasia were observed in ACI, but not COP, rats. These strain differences were not because of differences in circulating E2, progesterone or, prolactin. Two-thirds of the induced mammary cancers in ACI rats exhibited aneuploidy. The E2-induced mammary cancers regressed when hormone treatment was discontinued, indicating that they were estrogen-dependent. Progesterone receptor was expressed by the great majority of epithelial cells within the E2-induced atypical hyperplastic foci and the mammary carcinomas, suggesting a link between these lesions. These data demonstrate a correlation between E2 action in the induction of mammary cell proliferation and atypical epithelial hyperplasia and genetically conferred susceptibility to E2-induced mammary cancers.

Predominance of brain tumors in an extended Li-Fraumeni (SBLA) kindred, including a case of Sturge-Weber syndrome.

BACKGROUND: Li-Fraumeni syndrome (LFS) is characterized by a plethora of cancers, most prominent of which is carcinoma of the breast followed by sarcomas, brain tumors, leukemia, lymphoma, lung carcinoma, and adrenocortical carcinoma (therefore, also referred to by the acronym SBLA syndrome). METHODS: The family reported herein was first described 2 decades ago. Now extensive follow-up has shown the predictable occurrence of these tumor types, in addition to an excess of brain tumors and the finding of Sturge-Weber syndrome (SWS) in an LFS-affected family member. RESULTS: A possible new feature of the disorder, suggestive of SWS, was identified in a patient in the direct genetic lineage. This patient had a rhabdomyosarcoma of the eyelid at age 29 months and at age 14 years was diagnosed with lymphoblastic lymphoma/acute lymphoblastic leukemia. A remarkable excess of brain tumors was identified in this family through this current update. The p53 germ-line mutation was not identified in any affected member of this family. CONCLUSIONS: To the authors' knowledge, this is the first example of SWS in the context of LFS. Brain tumors appear to be an important component of the tumor spectrum of LFS, as evidenced in this family.

Estrogen-induced pituitary tumor development in the ACI rat not inhibited by dietary energy restriction.

We have demonstrated that a 40% restriction of dietary energy consumption virtually abolishes the development of prolactin (PRL)-producing pituitary tumors in Fischer 344 (F344) rats treated chronically with estrogen, apparently by inhibiting the ability of estrogen to enhance survival within a rapidly proliferating lactotroph population. The purpose of the study reported here was to determine whether energy restriction exerts a similar antitumorigenic action in another rat strain, August x Copenhagen-Irish (ACI), in which PRL-producing pituitary tumors develop in response to estrogen treatment. Ovariectomized female ACI rats were either allowed to consume a control diet ad libitum or were fed a modified diet that restricted energy consumption by 40% relative to the amount of energy consumed by animals fed the control diet. We also examined the ability of 17beta-estradiol (E2) administered for 20 wk via subcutaneous Silastic implants to induce development of PRL-producing pituitary tumors. Treatment with E2 increased pituitary weight as well as the pituitary weight-to-body weight ratio and induced gross hyperprolactinemia to the same extent in ACI rats fed either the control or the energy-restricted diet. Moreover, dietary energy restriction did not affect the ability of E2 to induce pituitary cell proliferation or inhibit apoptosis, as evidenced by quantification of two surrogate markers. These data provide compelling evidence that a 40% restriction of energy consumption does not inhibit the ability of E2 to induce pituitary tumor development in the ACI rat. In conjunction with our published studies of the F344 rat strain, the data presented herein indicate that the inhibitory effects of dietary energy restriction on estrogen-induced pituitary tumor development are rat-strain specific and suggest that sensitivity to specific antitumorigenic actions of energy restriction is strongly affected by genetic background.

Pediatric astrocytomas with monomorphous pilomyxoid features and a less favorable outcome.

Among tumors classified as pilocytic astrocytoma (PA) in the Johns Hopkins Hospital Department of Pathology files, we identified 18 cases with a distinctive monomorphous pilomyxoid histological pattern and a higher recurrence rate than that of PA with classical histological features (classical PA). The majority of the tumors occurred in infants and young children and involved the hypothalamic/chiasmatic region. The tumors were histologically similar to PA, but they were more monomorphous and more myxoid. Rosenthal fibers were not seen and only 1 of 18 tumors had eosinophilic granular bodies. At the end of the follow-up period, 6 patients were dead and 12 were alive with evidence of disease. Progression free survival (PFS) at 1 year was 38.7%. In comparison, we identified a control group of 13 classical PAs in the same age range and location as the study group. In this group, PFS at 1 year was 69.2%, which was significantly better than that for pilomyxoid tumors (p = 0.04). There was no CSF dissemination or death due to tumor progression among patients with classical PA. Eight of these patients are alive with recurrent disease, and 4 have no evidence of disease. While the monomorphous pilomyxoid tumors have some resemblance to classical PA, our results suggest that the former is a more aggressive variant or a separate entity that needs to be recognized for prognostic purposes.

Genetic bases of estrogen-induced pituitary growth in an intercross between the ACI and Copenhagen rat strains: dominant mendelian inheritance of the ACI phenotype.

Estrogens stimulate cell proliferation in a variety of tissues and are widely believed to be contributing factors in the etiology of certain cancer types in humans. The molecular mechanisms through which estrogens regulate cell proliferation are currently unknown. Estrogens stimulate proliferation of the PRL-producing lactotroph of the rat anterior pituitary gland and induce development of PRL-producing pituitary tumors in several inbred rat strains. Therefore, the lactotroph provides a well defined model for identifying the mechanisms through which estrogens regulate cell proliferation and/or survival. Data from our laboratory and others indicate that the relative sensitivity to the pituitary growth-promoting actions of estrogens is highly strain specific. This allows genetics-based approaches to be used to address the molecular mechanisms through which estrogens stimulate lactotroph proliferation and induce pituitary tumor development. In the present study we have examined the ability of diethylstilbestrol (DES) to induce pituitary growth in the genetically related AxC-Irish (ACI) and Copenhagen (COP) strains and their derived F1, F2, and backcross progeny. The data presented herein indicate that the anterior pituitary gland of the ACI strain displays approximately a 2-fold greater growth response to administered DES than does the pituitary gland of the COP strain. The average pituitary weight in male ACI rats was increased from 9.2 +/- 0.2 mg (mean +/- SD in untreated rats to 63.7 +/- 12.6 mg in rats treated with DES for 12 weeks, whereas in male COP rats, DES increased pituitary weight from 12.7 +/- 0.9 to 38.1 +/- 8.2 mg. The ACI phenotype was inherited in the F1, F2, and backcross progeny of an ACI x COP intercross as a dominant genetic trait, and the approximately 30 mg of additional pituitary growth displayed by the DES-treated ACI rat, relative to that of the treated COP rat, appeared to result from the actions of a single locus. Moreover, in F1 progeny from an ACI x Brown Norway intercross, the ACI phenotype was inherited as a dominant or incompletely dominant genetic trait. These data, when compared with findings of previous studies using the Fischer 344 rat strain, provide the first indication that distinct genetic pathways contribute to regulation of estrogen-induced pituitary growth and induction of PRL-producing pituitary tumors in the ACI and F344 rat strains.

Malignant supratentorial ganglioglioma (ganglion cell-giant cell glioblastoma): a case report and review of the literature.

BACKGROUND: From both epidemiologic and pathologic viewpoints, gangliogliomas exhibiting components of giant cell glioblastomas are extraordinary neoplasms. We report herein the case of a 6-year-old girl who presented initially with a World Health Organization grade IV anaplastic ganglioglioma (a mixed ganglion cell tumor-giant cell glioblastoma). Despite aggressive management, the patient died of disease in a relatively short period. METHODS: Formalin-fixed, paraffin-embedded tissue blocks were sectioned at 5 microm for histochemical and immunohistochemical analyses. Hematoxylin-eosin-stained sections and immunohistochemically stained sections from the primary and secondary resections were reviewed. Reactivity for glial fibrillary acidic protein, neurofilament protein, synaptophysin, and Ki67 nuclear antigen was evaluated. RESULTS: Histologically, 2 distinct cell populations were noted on both the primary and secondary resections. The primary resection revealed a neoplasm having a predominant glial component consistent with a glioblastoma. Interspersed were dysmorphic ganglion cells supporting a diagnosis of ganglioglioma. The second resection (following therapy) demonstrated a much more prominent dysmorphic ganglion cell component and a subdued glial component. CONCLUSION: Although immunohistochemical analysis clearly distinguished the 2 tumor cell populations, the identification of Nissl substance in neurons proved to be equally helpful. Although other cases of grade III gangliogliomas and rare cases of grade IV gangliogliomas have been reported, the present case is exceptional in that, to our knowledge, it is the only report of a patient who presented initially with a composite grade IV ganglioglioma and who was clinically followed up to the time of death. This case allows direct comparison between the histologic findings in a giant cell glioblastoma and a ganglioglioma and documents the aggressive biologic behavior of this complex neoplasm.

Modulation of estrogen action in the rat pituitary and mammary glands by dietary energy consumption.

We are investigating the mechanisms through which estrogens induce development of prolactin (PRL)-producing pituitary tumors and mammary carcinomas in rats and how these mechanisms are affected by dietary energy consumption. The hypothesis under examination is that dietary energy restriction inhibits tumorigenesis in estrogen-responsive tissues by altering cellular responsiveness to estrogenic hormones. In the Fischer 344 (F344) rat strain, a 40% restriction of energy consumption virtually abolishes development of estrogen-induced pituitary tumors. Inhibition of pituitary tumorigenesis in the F344 strain by energy restriction results from modulation of estrogen regulation of cell survival, not cell proliferation. In contrast, energy restriction has no inhibitory effect on estrogen-induced pituitary tumor development in the ACI rat strain. However, energy restriction markedly inhibits induction of mammary carcinomas in female ACI rats treated with 17beta-estradiol. Data presented herein indicate that dietary energy restriction modulates the responsiveness of specific cell populations to estrogenic hormones and thereby inhibits estrogen-induced tumorigenesis in a manner specific to both rat strain and tissue.