[Current status and challenges of accurate preoperative assessment of pancreatic cancer].

Pancreatic cancer is a malignant tumor with very poor prognosis. In the past decade, the surgical technique has made significant progress, but it has not brought desired effect in improving the survival outcome of pancreatic cancer patients. With the development of the concept of cancer treatment and the emergence of precision medicine, the surgical centered multidisciplinary treatment and collaborative diagnosis and treatment mode has gradually become the mainstream. Accurate preoperative assessment of pancreatic cancer has become a breakthrough for further improving the prognosis of patients with pancreatic cancer. From the perspective of precise assessment, this paper mainly summarized the status and progress on the following four aspects: the preoperative diagnosis and staging, the resectability evaluation, the neoadjuvant therapy strategy and efficacy evaluation of neoadjuvant therapy in pancreatic cancer, and also discussed the shortcomings and challenges in the field of precise assessment, finally in order to make the preoperative assessment of pancreatic cancer more precise and standard, and to provide useful reference for future research work.

Midazolam suppresses osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.

OBJECTIVE: Previous study showed that peripheral-type benzodiazepine receptors (PBRs) are expressed in human mesenchymal stem cells (hMSCs) and diazepam was found to inhibit hMCSs viability in high concentration. Midazolam, a benzodiazepine derivative, is widely used as an intravenous sedative in hospital. Peripheral-type benzodiazepine receptors (PBRs) affect a broad spectrum of cellular functions. We tested the cell viability and osteogenic differentiation of hMSCs. PATIENTS AND METHODS: Bone marrow was collected from 12 patients during the operation of spine internal fixation. Cultivated with basal medium, the hBMSCs were incubated with or without midazolam (0.1, 1, 5, 10, 15, 20 µM, respectively). Cell viability were tested with MTS assay after 2, 4, 6 hours respectively. Cell morphology was observed and recorded at 6 hour. After cultivated with osteogentic medium, the hBMSCs were incubated with or without midazolam (5, 10, 15, 20 µM, respectively). Alkaline phosphatase (ALP) activity and alizarin red S staining were measured. Cultivated with osteogentic medium with or without treatment of 15 µM midazolam, the mRNA expression of ALP, type 1 collagen (COL1), Runx2 and PPARγ was analyzed by real-time RT-PCR. RESULTS: The treatments of midazolam inhibited cell viability to 85%-16% respectively (p < 0.05). Rounded up phenomenon with floating cells, Membrane-blebbed cells and cytoplasmic contraction were observed after 10, 15 or 20 µM midazolam treatment. The ALP activity and Calcium deposition of hBMSCs exposed to 15 and 20 µM midazolam was significantly inhibited at 7, 14 and 21 days (p < 0.05). And the mRNA expression of ALP, COL1 and PPARγ was significantly suppressed in the hBMSCs cultured with 15 µM midazolam (p < 0.05). CONCLUSIONS: Midazolam exert negative effect on cell viability and osteogenic differentiation of cultured hBMSCs. During sedation in critical care, the use of midazolam may suppress activity of hBMSCs.

Screening for Oral Cavity Cancer: A 1-year Experience of a Regional Hospital in Taiwan.

INTRODUCTION: The purpose of this study was to analyze the risk factors affecting precancerous lesions, and cancer of oral cavity, and to assess efficacy of visual screening for oral mucosal lesions. METHODS: The medical records of patients older than 30 years of age with history of habitual cigarette smoking or betel quid chewing that received screening for oral mucosal lesions between January 2012 and December 2012 were retrospectively reviewed. The patients' age, gender, risk factors, screening findings, and histopathology results of biopsy were included for further analysis. RESULTS: A total of 1341 patients were enrolled in this study. There were 1080 males and 261 females ranging from 30 to 96 years of age, with a mean age of 53.9±13.6 years. After screening, 226 (16.9%) were found to be positive of oral lesions. Among these 226 patients, 69 (30.5%) underwent biopsy under local anesthesia, and the histopathology showed malignancy in 13 (5.8%). All of the confirmed malignant cases were squamous cell carcinoma. Among them, 12 received further staging examination and one was lost to follow-up resulting in unknown stage. The early stage oral cavity cancer (stage I and II) accounted for 84.6% (11/13). CONCLUSIONS: The detection rate of early stage oral cavity cancer in our study was reasonable. Therefore, visual screening for oral cavity cancer is recommended for patients with habitual cigarette smoking or betel quid chewing.

Intracellular zinc release-activated ERK-dependent GSK-3ß-p53 and Noxa-Mcl-1 signaling are both involved in cardiac ischemic-reperfusion injury.

Oxidative stress and nitrosative stress are both suggested to be involved in cardiac ischemia-reperfusion (I/R) injury. Using time-lapse confocal microscopy of cardiomyocytes and high-affinity O(2)(-•) and Zn(2+) probes, this study is the first to show that I/R, reactive oxygen species (ROS), and reactive nitrogen species (RNS) all cause a marked increase in the [O(2)(-•)](i), resulting in cytosolic and mitochondrial Zn(2+) release. Exposure to a cell-penetrating, high-affinity Zn(2+)(i) chelator, TPEN, largely abolished the Zn(2+)(i) release and markedly protected myocytes from I/R-, ROS-, RNS-, or Zn(2+)/K(+) (Zn(2+)(i) supplementation)-induced myocyte apoptosis for at least 24 h after TPEN removal. Flavonoids and U0126 (a MEK1/2 inhibitor) largely inhibited the myocyte apoptosis and the TPEN-sensitive I/R- or Zn(2+)(i) supplement-induced persistent extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, dephosphorylation of p-Ser9 on glycogen synthase kinase 3ß (GSK-3ß), and the translocation into and accumulation of p-Tyr216 GSK-3ß and p53 in, the nucleus. Silencing of GSK-3ß or p53 expression was cardioprotective, indicating that activation of the ERK-GSK-3ß-p53 signaling pathway is involved in Zn(2+)-sensitive myocyte death. Moreover, the ERK-dependent Noxa-myeloid cell leukemia-1 (Mcl-1) pathway is also involved, as silencing of Noxa expression was cardioprotective and U0126 abolished both the increase in Noxa expression and in Mcl-1 degradation. Thus, acute upstream Zn(2+)(i) chelation at the start of reperfusion and the use of natural products, that is, flavonoids, may be beneficial in the treatment of cardiac I/R injury.

MicroRNA-21 expression in neonatal blood associated with antenatal immunoglobulin E production and development of allergic rhinitis.

BACKGROUND: The prevalence of allergic diseases has increased in the past decades. It is unknown whether expression of certain microRNAs (miRNAs) in neonatal leucocytes is correlated to IgE production and/or allergic diseases. OBJECTIVE: This study investigated the association of miRNA expression in neonatal leucocytes with cord blood IgE (CBIgE) elevation and development of allergic disease. METHODS: We screened for the expression of a panel of 157 miRNAs in mononuclear leucocytes from human umbilical cord blood (CB) samples with elevated CBIgE and tracked the association of down-regulated miRNA expression to the miRNA-targeted gene expression and to children with allergic rhinitis (AR). RESULTS: Among the initial screen of 10 CB samples with elevated CBIgE, expression of eight of the 157 miRNAs was low. Of these eight down-expressed miRNAs, three remained down-regulation in a validation with other 20 CB samples, and two of the three miRNAs, miR-21 and miR-126, were significantly lower in monocytes from AR children. Further analysis of mRNA expression of the miR-21-targeted genes identified that TGFBR2 expression on monocytes was significantly up-regulated in CB with elevated CBIgE, and in AR patients. Transfection of miR-21 precursor into monocytes from patients with AR increased miR-21 expression and decreased TGFBR2 expression. CONCLUSION: This study demonstrated the first in the literature that lower miR-21 expression in CB and increased TGFBR2 expression is associated with antenatal IgE production and development of AR.

Interaction of maternal atopy, CTLA-4 gene polymorphism and gender on antenatal immunoglobulin E production.

BACKGROUND: Genetic heritability and maternal atopy have been correlated to antenatal IgE production, but very few studies have studied gene-maternal atopy interaction on antenatal IgE production. This study investigated the interaction of CTLA-4 polymorphism with prenatal factors on the elevation of cord blood IgE (CBIgE). METHODS: Pregnant women were antenatally recruited for collection of prenatal environmental factors by a questionnaire. Umbilical cord blood samples were collected for CBIgE detection by fluorescence-linked enzyme assay and CTLA-4 polymorphism measurement by restriction fragment length polymorphism. RESULTS: A total of 1104 pregnant women initially participated in this cohort study, and 898 of them completed cord blood collection. 21.4% of the newborns had elevation of CBIgE (>or=0.5 kU/L). The CTLA-4+49A allele (P=0.021), maternal atopy (P<0.001) and gender (P=0.034), but not the CTLA-4+49G allele, -318C allele, -318T allele, parental smoking or paternal atopy, were significantly correlated with the CBIgE elevation in multivariate analysis. A dichotomous analysis of gene-maternal atopy interactions identified maternal atopy and CTLA-4+49A allele had an additive effect on the CBIgE elevation, especially prominent in male newborns; and in the absence of maternal atopy, CTLA-4+49GG genotype had a protective effect on CBIgE elevation in female newborns. CONCLUSIONS: Maternal but not paternal atopy has significant impacts on CBIgE elevation depending on gender and CTLA-4+49A/G polymorphism of newborns. Control of maternal atopy and modulation of CTLA-4 expression in the prenatal stage may be a target for the early prevention of perinatal allergy sensitization.

Extracorporeal shock wave promotes growth and differentiation of bone-marrow stromal cells towards osteoprogenitors associated with induction of TGF-beta1.

Extracorporeal shock-wave (ESW) treatment has been shown to be effective in promoting the healing of fractures. We aimed to determine whether ESW could enhance the growth of bone-marrow osteoprogenitor cells. We applied ESW to the left femur of rats 10 mm above the knee at 0.16 mJ/mm2 in a range of between 250 and 2000 impulses. Bone-marrow cells were harvested after ESW for one day and subjected to assessment of colony-forming unit (CFU) granulocytes, monocytes, erythocytes, megakaryocytes (CFU-Mix), CFU-stromal cells (CFU-S) and CFU-osteoprogenitors (CFU-O). We found that the mean value for the CFU-O colonies after treatment with 500 impulses of ESW was 168.2 CFU-O/well (SEM 11.3) compared with 88.2 CFU-O/well (SEM 7.2) in the control group. By contrast, ESW treatment did not affect haematopoiesis as shown by the CFU-Mix (p = 0.557). Treatment with 250 and 500 impulses promoted CFU-O, but not CFU-Mix formations whereas treatment with more than 750 impulses had an inhibiting effect. Treatment with 500 impulses also enhanced the activity of bone alkaline phosphatase in the subculture of CFU-O (p<0.01), indicating a selective promotion of growth of osteoprogenitor cells. Similarly, formation of bone nodules in the long-term culture of bone-marrow osteoprogenitor cells was also significantly enhanced by ESW treatment with 500 impulses. The mean production of TGF-beta1 was 610 pg/ml (SEM 84.6) in culture supernatants from ESW-treated rats compared with 283 pg/ml (SEM 36.8) in the control group. Our findings suggest that optimal treatment with ESW could enhance rat bone-marrow stromal growth and differentiation towards osteoprogenitors presumably by induction of TGF-beta1.

Physical shock wave mediates membrane hyperpolarization and Ras activation for osteogenesis in human bone marrow stromal cells.

Physical shock wave (SW) has shown effectiveness on promotion of bone growth. We have recently demonstrated that SW could promote bone marrow stromal cell differentiation toward osteoprogenitor associated with induction of TGF-beta1. We have further demonstrated that SW-induced membrane hyperpolarization and Ras activation acted an early signal for the osteogenesis in human bone marrow stromal cells. An optimal dose of SW treatment at 0.16 mJ/mm(2) for 500 impulses induced a rapid membrane hyperpolarization in 5 min, activation of Ras in 30 min, and cell proliferation in 2 days. The SW-promoted cell growth was related to osteogenesis as demonstrated by increase of bone alkaline phosphatase activity in 6 days and osteocalcin mRNA expression in 12 days. In support that SW-induced Ras activation mediated osteogenesis of human bone marrow stromal cells, we further demonstrated that transfection of bone marrow stromal cells with a dominant negative Ras mutant (Asn-17 ras(H)) abrogated the SW enhancement of osteogenic transcription factor (CBFA1) activation, osteocalcin mRNA expression, and bone nodule formations. These results suggest that physical SW promotes bone marrow stromal cell differentiation toward osteogenic lineage via membrane hyperpolarization, followed by Ras activation and specific osteogenic transcription factor CBFA1 expression. A link between physical SW and biomembrane perturbation-mediated Ras activation may highlight how noninvasive physical agents could be used to promote fracture healing and to rescue patients with osteoporosis and osteopenic disorders in the future.

Constrictive pericarditis associated with Marlex mesh. Two case reports.

Two patients were referred to our hospital with constrictive pericarditis approximately 1 year after undergoing mitral valve repair at another institution. Both repairs had included the use of a pericardial substitute, Marlex mesh, to prevent adhesion and to facilitate possible reoperations. Computed tomography and cardiac catheterization were used to establish the diagnosis of constrictive pericarditis. During surgery, dense, thickened fibrous tissue, the result of a Marlex mesh-related reaction, was found tightly adhered to the epicardium in each of the patients. It appeared that the Marlex mesh, which had been inserted to facilitate reoperation, had contributed to the development of constrictive pericarditis.

Altered cellular but not humoral reactions in children with complicated enterovirus 71 infections in Taiwan.

Enterovirus 71 (EV 71) infections have high neurovirulence and fatality. Immune responses were assessed in 78 patients with EV 71 infection. EV 71 meningoencephalitis occurred more frequently in younger children and in boys. C-reactive protein levels were not elevated, although total leukocyte counts were increased in these patients. The CD40-ligand expression on T cells significantly decreased in children with meningoencephalitis (P=.041). Polymorphism of the cytotoxic T lymphocyte antigen-4 (CTLA-4) at position 49 of exon 1 showed a higher frequency of G/G genotype in patients with EV 71 meningoencephalitis than in those without meningoencephalitis (18/31 vs. 14/47; P=.045) and in control subjects (18/31 vs. 25/93l; P=.007). Specific EV 71 neutralizing antibody titers were detectable but did not differ in children with and without meningoencephalitis in the acute and convalescent stages. Results from this study suggest that younger children with a certain CTLA-4 polymorphism and altered cellular but not humoral response may be linked to EV 71 meningoencephalitis.

A model to study antioxidant regulation of endotoxemia-modulated neonatal granulopoiesis and granulocyte apoptosis.

Neonates with septicemia tend to develop granulocytopenia, which may, in part, be due to septic mediators such as oxygen free radicals and tumor necrosis factor alpha (TNF-alpha). Granulocytopenia may be caused by a decrease in granulocyte growth and/or an increase in granulocyte destruction. In the present study, we investigated antioxidant regulation of endotoxin-modulated neonatal granulopoiesis and granulocyte apoptosis. Using human umbilical cord blood (HUCB), we found that simulating endotoxemia in vitro elicited significant superoxide production within a few minutes. Endotoxin exposure suppressed colony-forming unit-granulocyte and monocyte formation in a dose-dependent fashion. Addition of antioxidants such as N-acetyl-cysteine could reverse the endotoxin suppression of colony-forming unit-granulocyte and monocyte formation (13 +/- 5 versus 75 +/- 5 colony-forming units/mL). Spontaneous in vitro granulocyte apoptosis in 6 h, as reflected by phosphatidylserine expression on the cell surface, was higher in granulocytes from HUCB than in those from adult blood (10.8 +/- 1.0% versus 5.6 +/- 1.2%). The addition of endotoxin or IL-8 to the cells in the in vitro model did not promote granulocyte apoptosis, but TNF-alpha, a major mediator of the effects of endotoxin, significantly induced granulocyte apoptosis in HUCB (control versus TNF-alpha: 8.9 +/- 1.2% versus 35.9 +/- 2.9%). Addition of the antioxidant N-acetyl-cysteine effectively blocked TNF-alpha-induced granulocyte apoptosis as demonstrated by DNA fragmentation. Results from these studies indicate that oxygen radicals are directly involved in endotoxin suppression of granulopoiesis, and indirectly promote granulocyte apoptosis, presumably through TNF-alpha-mediated action. Thus, under certain conditions, modulation of oxygen radical production in the blood may benefit neonates with granulocytopenia.

Effects of insulin on protein phosphorylation and protein kinase C activity in human malignant gliomas.

Modulation of protein phosphorylation activities by insulin was investigated in glioma and normal glial cells. Insulin suppressed the in vitro protein phosphorylation of glioma cells in a dose-dependent manner while it stimulated that of meningiomas, neurilemmomas and glial cells. Although gliomas and glial cells contained different species of tyrosyl phosphoproteins before treatment, they expressed similar kinds of tyrosyl phosphoproteins in response to insulin. Insulin increased the activities of casein kinase II and total protein kinase C (PKC) in glioma and normal glial cells. The membrane-bound PKC activity in U373-MG cells was elevated by insulin. The PKC isozymes, including subtypes alpha, beta, delta, epsilon and gamma, were detected in gliomas, but few were found in glial cells. Insulin down regulated the cytosolic PKC-gamma and the membrane-bound PKC-epsilon proteins in gliomas. These results indicate that an altered insulin signaling pathway exists in human gliomas, which might involve differential regulation of PKC isozymes.

Laser-induced fluorescence of pyrene and other polycyclic aromatic hydrocarbons (PAH) in seawater.

Polycyclic aromatic hydrocarbons (PAH) in the marine environment are currently of great concern due to their potential carcinogenicity. The standard methods of detection and quantification of PAH in seawater and sediments are costly, time-consuming and do not account for the heterogeneous nature of their distribution and sources. Laser-induced, time-resolved fluorescence spectroscopy may help to overcome these limitations. Several PAH have relatively long-lived stimulated fluorescence emissions, which allow them to be detected among a background of more intense but shorter-lived chromophores. Using time-delayed techniques we have shown an ability to detect PAH, principally pyrene, at environmental levels (ng l(-1)) both in the laboratory and in situ in Boston Harbor and other study areas. Further development may lead to the rapid determination of several PAH in typical near-shore marine environments.

Transient induction of apoptosis in serum-starved glioma cells by insulin and IGF-1.

Insulin has a wide variety of biological effects. One of them is a mitogen-like activity whereby cell proliferation is stimulated. In this study we found a heretofore unreported insulin-elicited transient apoptosis of glioma cells. When serum-starved glioma cells were fed with a fresh regular medium, in the 6- to 12-h post-starvation period, the growth rate as determined by cell number was significantly suppressed by insulin, although cell cycle progression and DNA synthesis were actually accelerated. Increase in apoptosis in those growth-retarded cultures was demonstrable by Hoechst staining, detection of histone-associated DNA fragment, and in situ cell death detection. Apoptosis occurred among cells in all stages of cell cycle. After 24 h post-starvation, insulin increased the total cell number like a typical growth-promoting mitogen. In this regard, IGF-1, but not EGF nor TGF-beta 1, behaved like insulin.

Weber syndrome caused by intracerebral hemorrhage in a hemophiliac boy.

A rare occurrence of the Weber syndrome in childhood is reported. The patient was a 7-year-old hemophiliac with recurrent intracerebral bleeding into the right cerebral peduncle and pontine base. Left hemiparesis involving the face and tongue developed and was later accompanied by right oculomotor nerve palsy.

[Pituitary apoplexy: a study of eighteen cases].

Pituitary Apoplexy is a rare but sometimes life threatening condition which requires prompt recognition and timely medical intervention to avoid catastrophic consequences. From January 1979 to June 1989 and total of one hundred and ninety eight pituitary tumor patients were operated on our hospital. Eighteen cases (9.1%) were diagnosed "pituitary apoplexy" according to histopathological findings. The group consisted of twelve men and six women ranging in age from twenty two to sixty one years with a mean of forty. There were three cases of prolactin-secreting adenomas (16.7%), four growth-hormone secreting adenomas (22.2%), and eleven nonfunctional adenomas (61.1%) with an incidence of 6.1%, 8.3%, and 11.4% respectively (P > 0.05). Clinical manifestation occurred acutely in 66.7% and nonacutely in 33.3%. The patients presented with headaches (100%), visual impairment (83.3%), visual field defects (66%), disturbed consciousness (22%), fever and meningismus (11%). Radiological examinations able to demonstrate abnormalities included plain skull films (84%), computed tomography (84.6%), and angiography (93.8%). Various investigations of endocrine function pre and post operatively showed a deficient gonad axis (53%, 62.5%), adrenal axis (26.7%, 56.2%), and thyroid axis (20%, 43.8%). Sixteen cases received a transsphenoid operation and three cases underwent a transfrontal craniotomy. No case of mortality was reported. Postoperative radiotherapy was given to nine cases and nine cases were followed up on a regular basis. Therefore, our retrospective study suggests that pituitary apoplexy is not uncommon and has an acute clinical presentation. No particular tumor type was prone to occur. Various radiological examinations could define perisellar abnormalities. With a decreasing order of hormone deficiency, gonad, adrenal and thyroid axis were observed during the course of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolactin effects on the dietary regulation of mouse mammary tumor virus proviral DNA expression.

Chronic energy-intake restriction inhibits mouse mammary tumor virus (MMTV)-induced mammary tumors in C3H/Ou mice by greater than 90%. We have shown that associated with suppression of mammary tumorigenesis there is a reduction or inhibition of circulating prolactin, MMTV particles expressed, and MMTV mRNA transcription in mammary glands (and in most organs tested). To understand the concerted action of prolactin, energy-consumption level, and MMTV on inducing mammary tumors, experiments were designed to control prolactin and energy levels in order to evaluate their effects on MMTV mRNA expression. Mice on restricted diets were grafted with adenohypophyses, and mice fed ad libitum were treated with the dopaminomimetic agent octahydrobenzo [g]quinoline. Adenohypophyseal grafting significantly increased prolactin in dietary (energy)-restricted mice, and this effect was associated with an increase in MMTV mRNA expression within the mammary gland; a linear correlation between prolactin levels and MMTV mRNA expression in the mammary gland was found. Conversely, elimination of the nocturnal peak of circulating prolactin by i.p. injection of dopaminomimetic octahydrobenzo [g]quinoline to mice fed ad libitum delayed (by 8 weeks) and reduced (even as long as 25 weeks) mammary gland MMTV mRNA expression. These findings associate prolactin influences with MMTV mRNA production in mice and help explain the link between chronic energy-intake restriction and reduced MMTV gene expression.

Suppression of mouse mammary tumor proviral DNA and protooncogene expression: association with nutritional regulation of mammary tumor development.

Chronic energy intake restriction (CEIR) reduces mouse mammary tumor virus (MMTV)-induced mammary tumors in C3H/Ou mice. Fewer than 10% of C3H/Ou mice developed mammary tumors during 88 wk of study when subjected to CEIR regardless of calorie source (fat vs. carbohydrate). By contrast, 100% of mice fed ad libitum diets relatively high in fat or carbohydrate or a commercial diet developed tumors by 35-40 wk. MMTV proviral DNA transcription was shown to be activated in spleen, liver, lung, kidney, small intestine, and mammary gland of mice consuming these diets ad libitum. By contrast, these messages were suppressed by CEIR in all tissues analyzed except spleen. MMTV proviral messages in liver and mammary gland increased with age in full-fed mice and were suppressed by CEIR. These findings suggest that the nutritional regulation of MMTV proviral DNA expression is tissue-specific. In CEIR mice the suppressed MMTV proviral DNA transcripts in mammary gland and liver increased with time in association with the delayed onset of mammary tumors. Mammary tumorigenesis in C3H mice is associated with integration of MMTV proviral DNA, which appears to activate a putative mammary tumor protooncogene, int-1. CEIR apparently decreases the frequency of viral reintegration adjacent to the int-1 gene and thus inhibits expression of int-1 and probably an initiation step in mammary tumorigenesis. Expression of other putative protooncogenes, int-2 and ras, in liver tissue was also reduced by CEIR. These findings indicate that both initiation and promotion of mammary tumorigenesis are influenced by CEIR in C3H/Ou mice.

Calorie consumption level influences development of C3H/Ou breast adenocarcinoma with indifference to calorie source.

To analyze simultaneously the influence attributable to calorie consumption level and percentage of dietary fat on the spontaneous development of mammary adenocarcinoma, virgin female C3H/Ou mice were separated into five dietary groups. Four groups of mice were fed purified diets either ad libitum (16-18 kcal/mouse/day) or restricted 40% in calorie consumption (10-11 kcal/mouse/day), and diets contained either 4.5%, 7.5%, 67%, or 68% calories from fat. Mice that consumed isocaloric diets developed breast malignancy at a comparable pace. Consuming a diet in which fats were present only at levels sufficient to satisfy the threshold requirement of essential fatty acids, 4.5-7.5% of the total calories, or alternatively where dietary fat represented greater than 67% of the total calories consumed, did not significantly alter the tendency for breast tumor development. The pace and frequency with which tumors occurred reflected the host's level of calorie consumption. Mice consuming a high caloric diet, low or high in fat, tended to have a shortened latency to breast tumor formation, an increased incidence of breast tumors, elevated serum prolactin levels, elevated levels of antibodies to mouse mammary tumor virus, and elevated circulating immune complex levels.