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Biomedical subjects

J Russo

Publications and source records attributed to J Russo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Selective estrogen receptor modulators. An aid in unraveling the links between estrogen and breast cancer.

Breast cancer is a classic hormone-dependent malignant disease that is influenced by estrogen. However, the molecular links between estrogen and cell proliferation in healthy and malignant breast tissue are complex and as yet not well understood. The selective estrogen receptor modulators (SERMs), which are competitive inhibitors of estrogen binding at estrogen receptors alpha and beta, have become important weapons in the prevention and treatment of breast cancer. These agents also offer opportunities for the elucidation of the multiple molecular mechanisms by which estrogen affects cell proliferation. Each SERM-estrogen receptor complex has a unique structure that influences its activity in different body tissues. Unraveling the links between SERM structure and function not only may shed light on the signaling pathways that connect estrogen to cell proliferation but also may allow the design of new agents specifically targeted to affect certain events along these pathways.

Breast Neoplasms↗
PubMed2001

The Cooperative Breast Cancer Tissue Resource: archival tissue for the investigation of tumor markers.

Investigators continue to search for reliable markers of prognosis of breast cancer. For many analyses, laboratory techniques permit the use of archival paraffin-embedded tissue collected years previously and readily linked to clinical and follow-up information. Laboratory investigators have often expressed the need for such a tissue resource. We have developed a publicly available resource of archival breast cancer specimens. The pathological material has been collected and reviewed by investigators at four institutions and currently includes breast cancer specimens from more than 9300 cases. Institutional pathologists reviewed slides and blocks using a common protocol and coding scheme. Clinical information and details of follow-up came from data routinely collected by the institutions' cancer registries. Coded data are maintained centrally in a single database. A subset of the data may be searched on the World Wide Web to determine the availability of cases with specified characteristics. The material collected by this Cooperative Breast Cancer Tissue Resource is generally representative of breast cancer diagnosed in community hospital settings in the United States. Seventy-two percent of the living cases have been followed for at least 5 years, and follow-up status is updated regularly. Interested laboratory investigators may apply to the Resource for the use of these tissues. This Resource is proving valuable to laboratory investigators who require large numbers of specimens for validation studies of prognostic markers of breast cancer.

Adult↗
PubMed2001

A meta-analysis of repetitive transcranial magnetic stimulation in the treatment of depression.

Repetitive transcranial magnetic stimulation (rTMS) is an emerging potential treatment for depression, but the data supporting its efficacy have not been systematically reviewed. The purpose of this study was to conduct a meta-analysis of rTMS trials in the treatment of depression. A search for all published and unpublished sham-controlled studies of left or right prefrontal cortical rTMS in the treatment of depression evaluated by the Hamilton Depression Rating Scale (HDRS) was conducted using no language restrictions. Fixed- and random-effects meta-analyses were performed on 12 studies comparing the decrease in HDRS scores achieved with rTMS and sham stimulation. Initial results with a fixed-effects analysis failed homogeneity testing; thus, a random-effects analysis was used to calculate all results. In 12 studies (16 individual effect sizes), the weighted mean effect size was 0.81 (95% CI: 0.42-1.20, P < .001). For studies using left dorsolateral pre-frontal cortex (DLPFC) stimulation (11 studies, 14 effect sizes), the weighted mean effect size was 0.89 (95% CI: 0.44-1.35, P < .001). For studies using left DLPFC stimulation in a parallel-groups design (seven studies, nine effect sizes), the weighted mean effect size was 0.88 (95% CI: 0.22-1.54, P < .01). No study showed a mean decrease in HDRS scores of > 50%, and the number of responders to rTMS (defined as a > 50% decrease in HDRS scores) across studies was relatively small (13.7% with rTMS versus 7.9% with sham stimulation). rTMS is statistically superior to sham stimulation in the treatment of depression, showing a moderate to large effect size. However, the clinical significance of these results is modest. The differences in response to rTMS across studies are not clearly explained, and, therefore, more research is needed.

Cerebral Cortex↗
PubMed2000

The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting.

NIH sponsored a meeting of medical and veterinary pathologists with mammary gland expertise in Annapolis in March 1999. Rapid development of mouse mammary models has accentuated the need for definitions of the mammary lesions in genetically engineered mice (GEM) and to assess their usefulness as models of human breast disease. The panel of nine pathologists independently reviewed material representing over 90% of the published systems. The GEM tumors were found to have: (1) phenotypes similar to those of non-GEM; (2) signature phenotypes specific to the transgene; and (3) some morphological similarities to the human disease. The current mouse mammary and human breast tumor classifications describe the majority of GEM lesions but unique morphologic lesions are found in many GEM. Since little information is available on the natural history of GEM lesions, a simple morphologic nomenclature is proposed that allows direct comparisons between models. Future progress requires rigorous application of guidelines covering pathologic examination of the mammary gland and the whole animal. Since the phenotype of the lesions is an essential component of their molecular pathology, funding agencies should adopt policies ensuring careful morphological evaluation of any funded research involving animal models. A pathologist should be part of each research team.

Animals↗
PubMed2000

Lipid and lipoprotein profiles, cardiovascular fitness, body composition, and diet during and after resistance, aerobic and combination training in young women.

The purpose of this study was to evaluate the effects of various modes of training on the time-course of changes in lipoprotein-lipid profiles in the blood, cardiovascular fitness, and body composition after 16 weeks of training and 6 weeks of detraining in young women. A group of 48 sedentary but healthy women [mean age 20.4 (SD 1) years] were matched and randomly placed into a control group (CG, n = 12), an aerobic training group (ATG, n = 12), a resistance training group (RTG, n = 12), or a cross-training group that combined both aerobic and resistance training (XTG, n = 12). The ATG, RTG and XTG trained for 16 weeks and were monitored for changes in blood concentrations of lipoprotein-lipids, cardiovascular fitness, body composition, and dietary composition throughout a 16 week period of training and 6 weeks of detraining. The ATG significantly reduced blood concentrations of triglycerides (TRI) (P < 0.05) and significantly increased blood concentrations of high-density lipoprotein-cholesterol (HDL-C) after 16 weeks of training. The correlation between percentage fat and HDL-C was 0.63 (P < 0.05), which explained 40% of the variation in HDL-C, while the correlation between maximal oxygen uptake (VO2max) and HDL-C was 0.48 (P < 0.05), which explained 23% of the variation in HDL-C. The ATG increased VO2max by 25% (P < 0.001) and decreased percentage body fat by 13% (P < 0.05) after 16 weeks. Each of the alterations in the ATG had disappeared after the 6 week detraining period. The concentration of total cholesterol (TC), TRI, HDL-C and low density lipoprotein-cholesterol in the blood did not change during the study in RTG, XTG and CG. The RTG increased upper and lower body strength by 29% (P < 0.001) and 38%, respectively. The 6 week detraining strength values obtained in RTG were significantly greater than those obtained at baseline. The XTG increased upper and lower body strength by 19% (P < 0.01) and 25% (P < 0.001), respectively. The 6 week detraining strength values obtained in XTG were significantly greater than those obtained at baseline. The RTG, XTG and CG did not demonstrate any significant changes in either VO2max, or body composition during the training and detraining periods. The results of this study suggest that aerobic-type exercise improves lipoprotein-lipid profiles, cardiorespiratory fitness and body composition in healthy, young women, while resistance training significantly improved upper and lower body strength only.

Adult↗
PubMed2000

Effects of parasitism and pesticide exposure on characteristics and functions of hemocyte populations in the freshwater snail Lymnaea palustris (Gastropoda, Pulmonata).

Morphological characteristics and functions of hemocytes were used to compare the immunological effects of biological and chemical stress in the freshwater snail Lymnaea palustris. Animals were either infected by a trematode parasite (Metaleptocephalus sp.), or exposed to environmental contaminants, namely atrazine and hexachlorobenzene (HCB). Three populations of circulating hemocytes, morphologically and cytochemically distinct (round cells, hyalinocytes, granulocytes), were identified in both control and parasitized or pesticide-exposed snails. After 6 h of exposure, HCB and atrazine resulted in 8-fold increases in the mean total number of hemocytes, whereas only a 2.2-fold increase was observed 6 h after cercaria emission in parasitized snails. The impact of HCB was limited to the first 24 h of exposure, whereas long-lasting effects of atrazine were observed. Hyalinocytes and, to a lesser extent, round cells contributed most to the increases in hemocyte density in pesticide-exposed snails. Parasitism and atrazine treatment resulted in significant increases of lectin-stained hemocytes, whereas exposure to HCB did not affect the percentages of stained and unstained cells. Hemocyte phagocytic activity increased in HCB-exposed snails but with no concomitant change of the oxidative burst. Opposite results were obtained in atrazine-treated snail hemocytes, with unchanged phagocytosis and decreased phorbol 12-myristate 13-acetate-stimulated production of reactive oxygen intermediates. No increase in phagocytosis, or in the production of reactive oxygen intermediates, was observed in hemocytes from parasitized snails. Infection with the immunologically compatible trematode parasite Metaleptocephalus sp. and exposure to atrazine generated similar reactions from circulating hemocytes, whereas a different response pattern was observed in HCB-exposed snails.

Animals↗
PubMed2000

Atlas and histologic classification of tumors of the rat mammary gland.

Studies performed in experimental animal models have demonstrated that mammary cancer is a complex multistep process that can be induced either by chemicals, radiation, viruses, or genetic factors. Rodent models have been useful for dissecting the initiation, promotion, and progression steps of mammary carcinogenesis. Chemically induced mammary tumors, such as those induced by 7,12-dimethylbenz(a)anthracene and N-methyl-N-nitrosourea, are, in general, hormone-dependent adenocarcinomas whose incidence, number of tumors per animal, tumor latency, and tumor type are influenced by the age, reproductive history, and endocrinologic milieu of the host at the time of carcinogen exposure as well as by diet and the dose of carcinogen administered. There is a need to classify tumors according to their histopathological type because those characteristics have implications in the interpretation of experimental data. In the classification presented here we attempt to provide a working framework for diagnosis of the type of lesions found in the mammary glands of rats treated with chemical carcinogens or radiation and to clarify criteria for establishing the basic biological characteristics of tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Predictors of outcome in a primary care depression trial.

OBJECTIVE: Previous treatment trials have found that approximately one third of depressed patients have persistent symptoms. We examined whether depression severity, comorbid psychiatric illness, and personality factors might play a role in this lack of response. DESIGN: Randomized trial of a stepped collaborative care intervention versus usual care. SETTING: HMO in Seattle, Wash. PATIENTS: Patients with major depression were stratified into severe (N = 149) and mild to moderate depression (N = 79) groups prior to randomization. INTERVENTIONS: A multifaceted intervention targeting patient, physician, and process of care, using collaborative management by a psychiatrist and primary care physician. MEASUREMENTS AND MAIN RESULTS: Patients with more severe depression had a higher risk for panic disorder (odds ratio [OR], 5.8), loneliness (OR, 2.6), and childhood emotional abuse (OR, 2.1). Among those with less severe depression, intervention patients showed significantly improved depression outcomes over time compared with those in usual care (z = -3.06, P<.002); however, this difference was not present in the more severely depressed groups (z = 0.61, NS). Although the group with severe depression showed differences between the intervention and control groups from baseline to 3 months that were similar to the group with less severe depression (during the acute phase of the intervention), these differences disappeared by 6 months. CONCLUSIONS: Initial depression severity, comorbid panic disorder, and other psychosocial vulnerabilities were associated with a decreased response to the collaborative care intervention. Although the intervention was appropriate for patients with moderate depression, individuals with higher levels of depression may require a longer continuation phase of therapy in order to achieve optimal depression outcomes.

Adult↗
PubMed2000

Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults.

Our objective was to compare the efficacy of the new wake-promoting drug modafinil to that of dextroamphetamine for the treatment of attention deficit hyperactivity disorder (ADHD) in adults. Twenty-two adults who met DSM-IV criteria for ADHD participated in a randomized, double-blind, placebo-controlled, three-phase crossover study comparing placebo, modafinil, and dextroamphetamine for the treatment of ADHD. The twice-daily study medications were titrated to doses of optimum efficacy over 4-7 days and then held constant during the rest of each 2-week treatment phase. Measures of improvement included the DSM-IV ADHD Behavior Checklist for Adults, the Controlled Oral Word Association Test (COWAT, using the letters C, F, and L version), Stroop, and Digit Span (Wechsler Adult Intelligence Scale version). For the 21 (96%) completers, the mean (+/- SD) optimum doses of modafinil and dextroamphetamine were 206.8 mg/day +/- 84.9 and 21.8 mg/day +/- 8.9, respectively. Scores on the DSM-IV ADHD Checklist (p < 0.001) were significantly improved over the placebo condition following treatment with both active medications. Performance on the COWAT (p < 0.05) reached trend levels of significance. Both medications were generally well tolerated. This preliminary study suggests that modafinil may be a viable alternative to conventional stimulants for the treatment of adults with ADHD.

Adolescent↗
PubMed2000

Activation of NF-kappaB/Rel occurs early during neoplastic transformation of mammary cells.

NF-kappaB/Rel is a family of transcription factors which are expressed in all cells; however, in most non-B cells, they are sequestered in the cytoplasm in inactive complexes with specific inhibitory proteins, termed IkappaBs. We have recently shown that NF-kappaB/Rel factors are aberrantly activated in human breast cancer and rodent mammary tumors, and function to promote tumor cell survival and proliferation. Here, we have examined the time-course of induction of NF-kappaB/Rel factors upon carcinogen treatment of female Sprague-Dawley (S-D) rats in vivo and in human mammary epithelial cells (HMECs) in culture. We observed that NF-kappaB/Rel activation is an early event, occurring prior to malignant transformation. In S-D rats, increased NF-kappaB/Rel binding was detected in nuclear extracts of mammary glands from 40% of animals 3 weeks post-treatment with 15 mg/kg 7,12-dimethylbenz[a]anthracene (DMBA); this is prior to formation of tumors which normally begin to be detected after 7-9 weeks. In non-tumorigenic MCF-10F cells, in vitro malignant transformation upon treatment with either DMBA or benzo[a]pyrene (B[a]P) resulted in a 4- to 12-fold increase in activity of classical NF-kappaB (p65/p50). NF-kappaB induction was corrrelated with a decrease in the stability of the NF-kappaB-specific inhibitory protein IkappaB-alpha. Ectopic expression of the transactivating p65 subunit of NF-kappaB in MCF-10F cells induced the c-myc oncogene promoter, which is driven by two NF-kappaB elements, and endogenous c-Myc levels. Furthermore, reduction mammoplasty-derived HMECs, immortalized following B[a]P exposure, showed dysregulated induction of classical NF-kappaB prior to malignant transformation. Together these findings suggest that activation of NF-kappaB plays an early, critical role in the carcinogen-driven transformation of mammary glands.

Animals↗
PubMed2000

Developmental, cellular, and molecular basis of human breast cancer.

Breast cancer, which is the most common neoplastic disease in females and accounts for up to one third of all new cases of women's cancer in North America, continues to rise in incidence. In addition, the mortality caused by this disease has remained almost unchanged for the past 5 decades, becoming only second to lung cancer as a cause of cancer-related death. The failure in eradicating this disease is largely due to the lack of identification of a specific etiologic agent, the precise time of initiation, and the molecular mechanisms responsible for cancer initiation and progression. Despite the numerous uncertainties surrounding the origin of cancer, there is substantial evidence that breast cancer risk relates to endocrinologic and reproductive factors. The development of breast cancer strongly depends on the ovary and on endocrine conditions modulated by ovarian function, such as early menarche, late menopause, and parity. However, the specific hormone or hormone combinations responsible for cancer initiation have not been identified, and their role as protective or risk factors is still incompletely understood. A highly significant female hormone is estrogen, which is involved in the development of a variety of cancers, but it is still unclear whether estrogens are carcinogenic to the human breast. An understanding of whether estrogens cause mutations, and, if so, whether they act through hormonal effects activated by receptor binding, cytochrome P450-mediated metabolic activation, or compromise the DNA repair system, is essential for determining whether this steroid hormone is involved in the initiation or progression of breast cancer. This knowledge has to be based on a multidisciplinary approach encompassing studies of the development of the breast, influence of hormones on the differentiation of individual structures, and their interrelations in the pathogenesis of breast cancer. The analysis of the mechanisms involved would require confirmation in the adequate in vitro models and determination of the role played by genomic alterations in both cancer initiation and progression.

Breast↗
PubMed2000

Shorter hospital stays and more rapid improvement among patients with schizophrenia and substance disorders.

OBJECTIVE: Length of stay and treatment response of inpatients with acute schizophrenia were examined to determine whether differences existed between those with and without comorbid substance-related problems. METHODS: The sample comprised 608 patients with a diagnosis of schizophrenia or schizoaffective disorder treated on hospital units with integrated dual diagnosis treatment. They were rated on admission and discharge by a psychiatrist using a structured clinical instrument. Patients with no substance-related problems were compared with those with moderate to severe problems using t tests, chi square tests, and analysis of variance. RESULTS: When analyses controlled for age, gender, and other clinical variables, dually diagnosed patients were found to have improved markedly faster compared with patients without a dual diagnosis. Their hospital stays were 30 percent shorter on both voluntary and involuntary units. They also showed somewhat greater symptomatic improvement and no increase in 18-month readmission rates. On admission the dual diagnosis group was more likely to be younger, male, and homeless and more likely to be a danger to self and others. Severity of psychosis was the same at admission for the two groups, but the dually diagnosed patients were rated as less psychotic at discharge. CONCLUSIONS: Dually diagnosed patients with schizophrenia appear to stabilize faster during acute hospitalization than those without a dual diagnosis. The authors hypothesize that substance abuse may temporarily amplify symptoms or that these patients may have a higher prevalence of better-prognosis schizophrenia. The availability of integrated dual-focus inpatient treatment and a well-developed outpatient system may also have helped these patients recover more rapidly.

Acute Disease↗
PubMed2000

S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo.

The mechanism of cell immortalization of human breast epithelial cells leading to neoplastic transformation is not clear. The isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10F, have provided a valuable tool to identify genes involved in this process. Using the technique of differential display, we have identified seven cDNA bands differentially displayed in the MCF-10F cells when compared with the mortal S130 cells from which MCF-10F was originated. One of these bands was isolated and cloned. Sequence analysis revealed 99% homology to the EF-hand calcium-binding protein S100P (Placental). The clone was overexpressed in the immortal cell line MCF-10F when compared to the mortal counterpart S130 or other primary cultures of human breast epithelial cells. In addition, it was highly expressed in chemically transformed breast epithelial cell lines (BP1E and D3. 1), breast cancer cell line T47D, as well as in three invasive ductal carcinomas when compared to their normal adjacent tissue. The S100P protein was localized by immunohistochemistry, using a monoclonal antibody against the same amino acid sequence of the gene cloned, in ductal hyperplasias, in situ and invasive ductal carcinoma, but not in the normal tissues. We concluded that S100P overexpression is an early event that might play an important role in the immortalization of human breast epithelial cells in vitro and tumor progression in vivo.

Base Sequence↗
PubMed2000

Hormonal approach to breast cancer prevention.

Breast cancer is more frequent in nulliparous women, while its incidence is significantly reduced by full-term pregnancy. The fact that the protection conferred by pregnancy is observed in women from different countries and ethnic groups, regardless of the endogenous incidence of this malignancy, indicates that this protection does not result from extrinsic factors specific to a particular environmental, genetic, or socioeconomic setting, but rather from an intrinsic effect of parity on the biology of the breast. Using an experimental system we have shown that treatment of young virgin rats with human chorionic gonadotropin (hCG), like full-term pregnancy, efficiently inhibits the initiation and progression of chemically induced mammary carcinomas. Treatment of young virgin rats with hCG induced a profuse lobular development of the mammary gland, reduced the proliferative activity of the mammary epithelium, and induced the synthesis of inhibin, a secreted protein with tumor-suppressor activity. HCG treatment also increased the expression of the programmed cell death (PCD) genes testosterone repressed prostate message 2 (TRPM2), interleukin 1-beta-converting enzyme (ICE), p53, c-myc, and bcl-XS, induced apoptosis, and downregulated cyclins. PCD genes were activated through a p53-dependent process, modulated by c-myc, and with partial dependence on the bcl-2 family-related genes. The possibility that this hormonal treatment activates known or new genes was tested by differential display technique. We have identified a series of new genes, hormone-induced-1 (HI-1) among them. The characterization of their functional role will contribute to clarify the mechanisms through which hCG inhibits the initiation and progression of mammary cancer. Of great significance was the observation that PCD genes remained activated even after lobular formations had regressed due to the cessation of hormone administration. We postulate that this mechanism plays a major role in the long-lasting protection exerted by hCG from chemically induced carcinogenesis, and might be also involved in the lifetime reduction in breast cancer risk induced in women by full-term pregnancy. The implications of these observations are two-fold: on one hand, they indicate that hCG, as pregnancy, may induce early genomic changes that control the progression of the differentiation pathway, and on the other, that these changes are permanently imprinted in the genome, regulating the long-lasting refractoriness to carcinogenesis. The permanence of these changes, in turn, makes them ideal surrogate markers of hCG effect in the evaluation of this hormone as a breast cancer preventive agent.

Animals↗
PubMed2000

Morphological phenotypes in neoplastic progression of human breast epithelial cells.

Neoplastic progression is a prolonged and stepwise process, while tumor growth occurs after a series of molecular alterations that culminate in tumorigenesis. The phenotypic changes of transformation in breast carcinogenesis were studied through the use of scanning and transmission electron microscopy. MCF 10F, a spontaneously immortalized human breast epithelial cell line (Soule et al., 1990), was treated with 7,12 dimethylbenz(a)anthracene (DMBA) (Calaf and Russo, 1993) and then transfected with the c-Ha-ras oncogene (Calaf et al., 1995). Treated cells showed a progression in altered morphology, anchorage independency, invasiveness and tumorigenicity in the SCID. Scanning and transmission electron microscopy illustrated that the transformed cells could be distinguished from control cells by the expression of morphological characteristics such as loss of contact inhibition, irregular size and shape, emission of long filopodia and formation of stratified layers. In contrast, control cells showed uniform, flattened and polyhedrical cells, well closely juxtaposed to each other and joined by cytoplasmic interdigitations. Control cells also did not form colonies in agar-methocel, and were not invasive or tumorigenic in SCID mice. These studies showed the progression of breast carcinogenesis by phenotypical changes induced by the carcinogen and the insertion of the c-Ha-ras oncogene.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Morphological phenotypes in neoplastic progression of benz(alpha)pyrene-treated breast epithelial cells.

The neoplastic conversion of a normal cell to a malignant one is a multistage process that occurs after a series of molecular alterations. Several chemical and physical agents can alter the morphology of different types of cells. Scanning and transmission electron microscopy have been valuable in evaluating changes that occur in the progression of transformation. MCF-10F, a spontaneously immortalized human breast epithelial cell line (Soule et al., 1990), was treated with benz(alpha)pyrene (BP) (Calaf and Russo, 1993) and then transfected with the c-Ha-ras oncogene (Calaf et al., 1995). The phenotypic changes of breast cancer progression were studied through the use of scanning and transmission electron microscopy. Activated oncogenes have been detected in a variety of malignant tumors and the altered expression of certain genes seems to play a role in the cancer process. Carcinogen-treated and transfected cells showed a progression of changes in the morphology, anchorage independent growth, invasiveness and capability of tumor formation in the SCID mice. This in vitro cancer model can parallel the progression of breast cancer seen through molecular changes that occur and have been observed during the natural development of this disease.

Animals↗
PubMed1999

Apoptosis and catastrophic cell death in benzo[a]pyrene-transformed human breast epithelial cells.

Apoptosis and mitotic death, bi- and multinucleation, giant cells and micronucleation were investigated in human breast epithelial cell lines transformed by benzo[a]pyrene (BP) (BP1, BP1-E and BP1-E1 cells) and in BP1 cells transfected with the c-Ha-ras oncogene (BP1-Tras cells). Since BP induces apoptosis and the abnormal expression of ras genes elicits catastrophic mitosis, both cell death phenomena were expected to occur in this system, especially in BP1-Tras cells. Regardless of the cell line considered, single-nucleate cells were found to be eliminated preferentially through apoptosis, while bi- and multinucleate cells were eliminated through catastrophic mitosis. Apoptosis and catastrophic mitosis were observed in all cell lines but were significantly more frequent in BP1-Tras cells. The abnormal expression of Ha-ras in the latter cells may enhance in this system the effects of the BP apoptosis path reported for BP-transformed Hepa 1c1c7 hepatoma cells. Transfection with the ras oncogene also enhanced the mitotic disturbances, which produced multi- and micronucleation and mitotic death, possibly because of the genomic instability promoted by this oncogene in the BP-transformed cell line.

Apoptosis↗