			Home About us Contact

Mitotic Index (mitotic + index)

Distribution by Scientific Domains

Medical Sciences	48%
Life Sciences	37%
Chemistry	10%

Distribution within Medical Sciences

Pathology	27%
Hepatology	20%
Oncology & Radiotherapy	10%

Selected Abstracts

Developmental changes in cell proliferation in the auditory midbrain of the bullfrog, Rana catesbeiana

DEVELOPMENTAL NEUROBIOLOGY, Issue 11 2006
Andrea Megela Simmons
Abstract We examined patterns of cell proliferation in the auditory midbrain (torus semicircularis) of the bullfrog, Rana catesbeiana, over larval and early postmetamorphic development, by visualizing incorporation of 5-bromo-2,-deoxyuridine (BrdU) in cycling cells. At all developmental stages, BrdU-labeled cells were concentrated around the optic ventricle. BrdU-labeled cells also appeared within the torus semicircularis itself, in a stage-specific manner. The mitotic index, quantified as the percent of BrdU-positive cells outside the ventricular zone per total cells available for label, varied over larval development. Mitotic index was low in hatchling, early larval, and late larval stages, and increased significantly in deaf period, metamorphic climax, and froglet stages. Cell proliferation was higher in metamorphic climax than at other stages, suggesting increased cell proliferation in preparation for the transition from an aquatic to an amphibious existence. The change in mitotic index over development did not parallel the change in the total numbers of cells available for label. BrdU incorporation was additionally quantified by dot-blot assay, showing that BrdU is available for label up to 72 h postinjection. The pattern of change in cell proliferation in the torus semicircularis differs from that in the auditory medulla (dorsal medullary nucleus and superior olivary nucleus), suggesting that cell proliferation in these distinct auditory nuclei is mediated by different underlying mechanisms. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 1212,1224, 2006 [source]

Aluminum induces chromosome aberrations, micronuclei, and cell cycle dysfunction in root cells of Vicia faba

ENVIRONMENTAL TOXICOLOGY, Issue 2 2010
Min Yi
Abstract Aluminum (Al) exists naturally in air, water, and soil, and also in our diet. Al can be absorbed into the human body and accumulates in different tissues, which has been linked to the occurrence of Alzheimer's disease and various neurological disorders. By using Vicia cytogenetic tests, which are commonly used to monitor the genotoxicity of environmental pollutants, cytogenetic effects of aluminum (AlCl3) were investigated in this study. Present results showed that Al caused significant increases in the frequencies of micronuclei (MN) and anaphase chromosome aberrations in Vicia faba root tips exposed to Al over a concentration-tested range of 0.01,10 mM for 12 h. The frequency of micronucleated cells was higher in Al-treated groups at pH 4.5 than that at pH 5.8. Similarly, AlCl3 treatment caused a decrease in the number of mitotic cells in a dose- and pH-dependent manner. The number of cells in each mitotic phase changed in Al-treated samples. Mitotic indices (MI) decreased with the increases of pycnotic cells. Our results demonstrate that aluminum chloride is a clear clastogenic/genotoxic and cytotoxic agent in Vicia root cells. The V. faba cytogenetic test could be used for the genotoxicity monitoring of aluminum water contamination. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010. [source]

Sex Hormone Dependency of Diethylnitrosamine-induced Liver Tumors in Mice and Chemoprevention by Leuprorelin

CANCER SCIENCE, Issue 3 2001
Tamaki Nakatani
The prevalence of liver tumors throughout the world makes it imperative to seek chemopreventive agents. This tumor appears to be hormone-responsive and hormonal manipulations may therefore be beneficial. On this basis, both sexes of 12-day-old B6C3FJ mice were injected i.p. with diethylnitrosamine (DEN) at the dose of 2.5 ,g/g body weight and observed for 32 weeks (males) or 36 weeks (females). In 100% of male mice, liver tumors were observed with an average diameter of 2.72 mm and multiplicity of 60.8. Orchidectomy at 6 weeks of age in these mice inhibited the incidence, multiplicity and size to 63%, 5.6 and 1.54 mm, respectively. By further implantation with an E2 pellet at monthly intervals, these parameters were reduced to 26%, 0.6 and 0.61 mm, respectively. Administration of a gonadotropin-blocking chemical, leuprorelin, to DEN-treated male mice significantly reduced the multiplicity and size of tumors to 18.3 and 2.54 mm (P<0.01 compared to those of DEN only). In female mice, the incidence of liver tumor was significantly smaller than that of males. However, ovariectomy and/or testosterone supplement significantly increased the occurrence of liver tumor. An anti-estrogen, toremifene, caused a marked further decrease of liver tumors. Mitotic indices with bromodeoxyuridine in tumor tissues paralleled the occurrence of liver tumors. Serum testosterone levels were significantly reduced by orchidectomy or by leuprorelin administration. These results further confirm that liver tumor is testosterone-responsive and hormonal manipulation by surgical orchidectomy or by chemical orchidectomy i.e. by leuprorelin, could substantially prevent the appearance of liver tumors. [source]

Developmental changes in cell proliferation in the auditory midbrain of the bullfrog, Rana catesbeiana

Assessment of the predictive value of clinical and histopathological factors as well as the immunoexpression of p53 and bcl-2 proteins in response to preoperative chemotherapy for esophageal squamous cell carcinoma

DISEASES OF THE ESOPHAGUS, Issue 3 2000
J. Szumilo
The aim of the study was to determine the predictive value of selected clinical and histopathological factors as well as the immunohistochemical expression of p53 and bcl-2 proteins in the prediction of the pathological response to preoperative chemotherapy in esophageal squamous cell carcinoma. Thirty-four patients with advanced squamous cell carcinoma of the thoracic esophagus (T2,4 N0,1 M0), who underwent one cycle of cisplatin and 5-fluorouracil therapy followed by subtotal esophagectomy, were studied. All clinical factors (tumor longitudinal diameter in a computed tomographic scan, invasion depth, the presence of lymph node metastasis and clinical tumor staging) were evaluated before the onset of the therapy. The histopathological features (grade of differentiation, degree of keratinization, nuclear polymorphism, mitotic index, pattern of cancer invasion and inflammatory response), and the expression of p53 and bcl-2 proteins were also estimated in prechemotherapy endoscopic biopsy specimens. Pathological response to chemotherapy was assessed in surgically resected specimens. Of 34 patients, two (5.9%) showed complete response (CR), six patients (17.6%) exhibited major histological changes (partial response 1; PR1), 24 (70.6%) showed minor histological changes (partial response 2; PR2), and two patients (5.9%) exhibited no response to chemotherapy (stable disease; SD). There were no significant relationships between the response to preoperative chemotherapy (CR + PR1 vs. PR2 + SD) and the majority of the clinical and all the histopathological features. Deeper cancer invasion before chemotherapy was the only factor that tended to worsen the therapy effect (p < 0.01). The pathological response to treatment had no significant associations with the expression of p53 and bcl-2 proteins in esophageal squamous cell carcinoma. It should be noted, however, that both patients in CR were p53 and bcl-2 protein-negative. [source]

Cytogenetic effects of commercial formulations of deltamethrin and/or isoproturon on human peripheral lymphocytes and mouse bone marrow cells

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2007
Lalit K.S. Chauhan
Abstract The cytogenetic effects of deltamethrin (DEL) and/or isoproturon (ISO) were examined in human lymphocytes and mouse bone marrow cells. Peripheral lymphocytes were exposed to DEL (2.5, 5, 10, or 20 ,M), ISO (25, 50, 100, or 200,M), or DEL + ISO (2.5 + 25, 5 + 50, 10 + 100, or 20 + 200 ,M) and cytogenic effects were evaluated via chromosomal aberrations (CA) and the cytokinesis-block micronucleus assay (CBMN). Mice were orally gavaged to single dose of DEL (6.6 mg/kg), ISO (670 mg/kg), or DEL+ISO (6.6 + 670 mg/kg) for 24 hr or to DEL (3.3 mg/kg/day), ISO (330 mg/kg/day), or DEL + ISO (3.3 + 330 mg/kg/day) for 30 days and analyzed for CA. DEL induced a significant frequency of CA at 10 ,M whereas ISO (25,100,M) alone, or in combination with DEL, did not show any significant effect. Micronucleus (MN) induction was observed to be concentration-dependent though significant frequencies were observed at 5 ,M DEL, 100 ,M ISO, or 5 + 50 ,M DEL + ISO. In mice, DEL inhibited the mitotic index (MI) significantly (P < 0.001) at 24 hr while ISO alone, or in combination with DEL, did not cause any statistically significant effect. Following a 24 hr exposure, DEL and ISO alone induced significant (P < 0.01) frequencies of CA, whereas DEL + ISO in combination did not. Furthermore, 30 days exposure of ISO significantly inhibited the MI (P < 0.02 or < 0.01) and induced CA while DEL alone, or in combination with ISO, resulted in no significant effect on CA or the MI. The present findings indicate that the in vitro and in vivo exposure of a commercial formulation of DEL can cause genotoxic effects in mammals. However, the coexposure of DEL and ISO did not show additive effects, but instead demonstrated somewhat reduced genotoxicity. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc. [source]

Acute exposure of human lung cells to 1,3-butadiene diepoxide results in G1 and G2 cell cycle arrest

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2005
Michael Schmiederer
Abstract 1,3-butadiene (BD) causes genetic damage, including adduct formation, sister chomatid exchange, and point mutations. Previous studies have focused on the types of genetic damage and tumors found after long-term exposure of rodents to butadiene. This study examined the effect of the most active BD metabolite, butadiene diepoxide (BDO2), on cell cycle entry and progression in human lung fibroblasts (LU cells) with a normal diploid karyotype. Serum-arrested (G0) LU cells were exposed to BDO2 for 1 hr and stimulated to divide with medium containing 10% fetal bovine serum. The BDO2 -treated LU cells were evaluated for cell cycle progression, nuclear localization of arrest mediators, mitotic index, and cellular proliferation. The BDO2 -treated cells demonstrated a substantial inhibition of cell proliferation when treated with 100 ,M BDO2 for 1 hr. No appreciable levels of apoptosis or mitotic figures were observed in the BDO2 -treated cells through 96 hr posttreatment. Flow cytometric analysis revealed that the lack of proliferation in BDO2 -treated LU cells was related to G1 arrest in about half of the cells and a delayed progression through S and G2 arrest in nearly all of the remaining cells. Both G1 and G2 arrest were prolonged and only a very small percentage of BDO2 -treated cells were eventually able to replicate. Increased nuclear localization of both p53 and p21cip1 was observed in BDO2 -treated cells, suggesting that the cell cycle arrest was p21cip1 -mediated. These results demonstrate that BDO2 induces cell cycle perturbation and arrest even with short-term exposure that does not produce other pathologic cellular effects. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source]

Cell cycle effects resulting from inhibition of hepatocyte growth factor and its receptor c-Met in regenerating rat livers by RNA interference,

HEPATOLOGY, Issue 6 2007
Shirish Paranjpe
Hepatocyte growth factor (HGF) and its receptor c-Met are involved in liver regeneration. The role of HGF and c-Met in liver regeneration in rat following two-thirds partial hepatectomy (PHx) was investigated using RNA interference to silence HGF and c-Met in separate experiments. A mixture of 2 c-Met-specific short hairpin RNA (ShRNA) sequences, ShM1 and ShM2, and 3 HGF-specific ShRNA, ShH1, ShH3, and ShH4, were complexed with linear polyethylenimine. Rats were injected with the ShRNA/PEI complex 24 hours before and at the time of PHx. A mismatch and a scrambled ShRNA served as negative controls. ShRNA treatment resulted in suppression of c-Met and HGF mRNA and protein compared with that in controls. The regenerative response was assessed by PCNA, mitotic index, and BrdU labeling. Treatment with the ShHGF mixture resulted in moderate suppression of hepatocyte proliferation. Immunohistochemical analysis revealed severe suppression of incorporation of BrdU and complete absence of mitosis in rats treated with ShMet 24 hours after PHx compared with that in controls. Gene array analyses indicated abnormal expression patterns in many cell-cycle- and apoptosis-related genes. The active form of caspase 3 was seen to increase in ShMet-treated rats. The TUNEL assay indicated a slight increase in apoptosis in ShMet-treated rats compared with that in controls. Conclusion: The data indicated that in vivo silencing of c-Met and HGF mRNA by RNA interference in normal rats results in suppression of mRNA and protein, which had a measurable effect on proliferation kinetics associated with liver regeneration. (HEPATOLOGY 2007.) [source]

Cellular responses in experimental liver injury: Possible cellular origins of regenerative stem-like progenitor cells,

HEPATOLOGY, Issue 5 2005
William B. Coleman Ph.D.
Background/Aims Mature hepatocytes divide to restore liver mass after injury. However, when hepatocyte division is impaired by retrorsine poisoning, regeneration proceeds from another cell type: the small hepatocyte-like progenitor cells (SHPCs). Our aim was to test whether SHPCs could originate from mature hepatocytes. Methods Mature hepatocytes were genetically labeled using retroviral vectors harboring the ,-galactosidase gene. After labeling, retrorsine was administered to rats followed by partial hepatectomy to trigger regeneration. A liver biopsy was performed one month after surgery and rats were sacrificed one month later. Results We observed the proliferation of small hepatocytes arranged in clusters in liver biopsies. These cells expressed Ki67 antigen and displayed high mitotic index. At sacrifice, regeneration was completed and clusters had merged. A significant proportion of clusters also expressed ,-galactosidase demonstrating their origin from labeled mature hepatocytes. Finally, the overall proportion of ,-galactosidase positive cells was identical at the time of hepatectomy as well as in liver biopsy and at sacrifice. Conclusions The constant proportion of ,-galactosidase positive cells during the regeneration process demonstrates that mature hepatocytes are randomly recruited to proliferate and compensate parenchyma loss in this model. Furthermore, mature hepatocytes are the source of SHPC after retrorsine injury. [source]

Cell proliferation and cell cycle control: a mini review

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2004
C.H. Golias
Summary Tumourigenesis is the result of cell cycle disorganisation, leading to an uncontrolled cellular proliferation. Specific cellular processes-mechanisms that control cell cycle progression and checkpoint traversation through the intermitotic phases are deregulated. Normally, these events are highly conserved due to the existence of conservatory mechanisms and molecules such as cell cycle genes and their products: cyclins, cyclin dependent kinases (Cdks), Cdk inhibitors (CKI) and extra cellular factors (i.e. growth factors). Revolutionary techniques using laser cytometry and commercial software are available to quantify and evaluate cell cycle processes and cellular growth. S-phase fraction measurements, including ploidy values, using histograms and estimation of indices such as the mitotic index and tumour-doubling time indices, provide adequate information to the clinician to evaluate tumour aggressiveness, prognosis and the strategies for radiotherapy and chemotherapy in experimental researches. [source]

Genotoxicity study in lymphocytes of offset printing workers

JOURNAL OF APPLIED TOXICOLOGY, Issue 1 2006
Hüseyin Aksoy
Abstract The potential cytogenetic damage in offset printing workers was evaluated using sister chromatid exchanges (SCEs), chromosome aberrations (CAs) and micronuclei (MN) as biomarkers in peripheral lymphocytes of 26 volunteers (14 workers, 12 controls). The CA, SCE and MN frequency of offset printing workers was significantly higher than in their controls. The replication index (RI) was not affected while the mitotic index (MI) was affected most in the workers. It can be concluded from this study that chronic occupational exposure to printing dyes and thinner may lead to a slightly increased risk of genetic damage among offset printing workers. Copyright © 2005 John Wiley & Sons, Ltd. [source]

In vitro and in vivo tumor growth inhibition by a p16-mimicking peptide in p16INK4A -defective, pRb-positive human melanoma cells

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005
Douglas M. Noonan
The cell cycle regulatory pathway responsible for the control of the late-G1 checkpoint is found recurrently altered in human malignant melanoma, often due to lack of functional p16 or pRb (pRb-1) proteins. Here we examined the ability of p16-derived peptides to mimic p16 function in two exemplary human melanoma cell lines: the p16-defective, pRb-positive A375M cells and p16-positive, pRb-defective A2058 cells. The synthetic p16-mimicking peptides strongly induced apoptosis in p16,, pRb+ A375M cells in vitro, while they had significantly less activity on p16+, pRb, A2058 cells. The most active p16-mimicking peptide, p16-AP9, also potently inhibited in vivo growth of the A375M melanoma. Treated tumors showed a threefold smaller volume (P,<,0.025) and a significant reduction of the mitotic index and of PCNA expression. Growth of A2058 cells in vivo was not affected by treatment with the p16-mimicking peptide. Our results demonstrate that p16-mimicking peptides can induce apoptosis in vitro and that can inhibit tumor growth in vivo in p16-defective, pRb-expressing human melanoma cells, suggesting that p16-mimicking peptides can represent a promising tool for targeted therapy in selected cancer phenotypes. © 2004 Wiley-Liss, Inc. [source]

Significance of cell kinetic parameters in the prognosis of malignant melanoma: a review

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2007
Pierre Vereecken
The maximum tumor thickness as measured by Breslow's method is the cornerstone prognostic criterion, but despite this, evolution of the disease in some patients remains unpredictable, confirming that new reliable prognostic factors are awaited. Cell kinetic evaluation has been shown to be a useful tool for assessing the prognosis of breast and gastrointestinal cancer patients. Indeed, in these fields, the mitotic index and MIB-1 expression index, which are indirect estimates of the growth fraction of tumor cell population, are commonly shown to correlate with tumor grade and patient survival and presented as prognostic factors. In melanoma, results of cell kinetic investigations are conflicting: some studies have established a link between high proliferative activity and a bad prognosis, whereas other reports suggest the opposite. The aim of this review is to discuss these findings. [source]

Evaluation of the Genotoxicity of Chitosan Nanoparticles for Use in Food Packaging Films

JOURNAL OF FOOD SCIENCE, Issue 6 2010
Renata De Lima
Abstract:, The use of nanoparticles in food packaging has been proposed on the basis that it could improve protection of foods by, for example, reducing permeation of gases, minimizing odor loss, and increasing mechanical strength and thermal stability. Consequently, the impacts of such nanoparticles on organisms and on the environment need to be investigated to ensure their safe use. In an earlier study, Moura and others (2008a) described the effect of addition of chitosan (CS) and poly(methacrylic acid) (PMAA) nanoparticles on the mechanical properties, water vapor, and oxygen permeability of hydroxypropyl methylcellulose films used in food packaging. Here, the genotoxicity of different polymeric CS/PMAA nanoparticles (size 60, 82, and 111 nm) was evaluated at different concentration levels, using the,Allium cepa,chromosome damage test as well as cytogenetic tests employing human lymphocyte cultures. Test substrates were exposed to solutions containing nanoparticles at polymer mass concentrations of 1.8, 18, and 180 mg/L. Results showed no evidence of DNA damage caused by the nanoparticles (no significant numerical or structural changes were observed), however the 82 and 111 nm nanoparticles reduced mitotic index values at the highest concentration tested (180 mg/L), indicating that the nanoparticles were toxic to the cells used at this concentration. In the case of the 60 nm CS/PMAA nanoparticles, no significant changes in the mitotic index were observed at the concentration levels tested, indicating that these particles were not toxic. The techniques used show promising potential for application in tests of nanoparticle safety envisaging the future use of these materials in food packaging. [source]

Mutagenicity and Safety Evaluation of Water Extract of,Coriander sativum,Leaves

JOURNAL OF FOOD SCIENCE, Issue 1 2010
Mariana Ramírez Reyes
ABSTRACT:, Coriander has been used as a spice and medicinal plant for centuries. Several studies have described its biological properties and some reports have indicated its pharmacological actions in some human pathology. However, data on its toxicity and metabolism are limited or null, and no research has been conducted with mammalian cells. The purpose of this study was to evaluate the mutagenicity and safety of,Coriandrum sativum,extract. The mutagenic effects of,C. sativum,extract were evaluated by Ames test. Mutagenicity was present when the,C. sativum,extract was used in high concentrations in both tested strains (Salmonella typhimurium,TA97 and TA102). Our research showed that,C. sativum,extract reduced the cell survival of human cell lines (WRL-68 and 293Q cells) by inducing apoptosis and necrosis in the cases where extract concentration was the highest. The,C. sativum,extract altered the cell cycle; it increased the G1 phase of hepatic cells and reduced the G2+M phase in both cell lines in a dose-response manner. These results showed correlation with a reduction in the mitotic index. The extract also induced severe malformations during embryonic development. Exposure of chicken embryos to the,C. sativum,extract resulted in a dose-dependent increase of anomalies. Present results show that,C. sativum,extract reduced the axial skeleton and affected the neural tube, the somites, the cardiovascular structures, and the eye. According to the present results, the,C. sativum,aqueous extract cannot be considered safe. These results indicate that some significant adverse effects of,C. sativum,extract could be observed,in vivo. [source]

The Trophic Effects of Oestrogen on Male Rat Anterior Pituitary Lactotrophs

JOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2009
L. A. Nolan
Rapid but often transient changes in mitotic and apoptotic activity are important components of the pituitary response to changes in the hormonal environment. For example, bilateral adrenalectomy and orchidectomy each result in a wave of increased mitosis lasting approximately 1 week, mediated by the same population of trophically active and, to a large extent, endocrinologically inactive cells. By contrast to these tonic inhibitors of pituitary trophic activity, reports of a progressive increase in lactotroph numbers during pregnancy suggest that oestrogen is a potent and persistent pituitary mitogen. By comparing the amplitude and duration of male rat anterior pituitary mitotic responses to oestrogen treatment, to adrenalectomy, and to a combination of the two, the present study aimed to further clarify the characteristics of the oestrogen-induced trophic response, in particular whether lactotrophs are the predominant cell type involved. Adrenalectomy produced a wave of increased mitotic activity, which resolved within 7 days as expected, whereas oestrogen induced a significant increase in mitotic activity, which was sustained for the 14-day duration of the study. The trophic effects of combining adrenalectomy and oestrogen treatment were not additive in that the statistically insignificant upward trend in mitotic index during the first few days compared to oestrogen treatment alone was entirely abolished by oestrogen pre-treatment. The increase in mitotic activity in lactotrophs induced by oestrogen either with or without adrenalectomy did not result in an increase in the relative size of the prolactin-positive compared to prolactin-negative pituitary parenchymal cell numbers by the end of the study. Despite the marked increase in the lactotroph population that is reported during pregnancy, these data indicate that at least the early (i.e. within 2 weeks) mitotic response to pharmacological doses of oestrogen increases mitotic activity in the lactotroph subpopulation by only 5,8% relative to other cellular subpopulations. Unexpectedly, the mitotic response to oestrogen principally occurs in non-prolactin-containing cells and results in the recruitment, amongst other trophically responsive populations, of the entire subpopulation of prolactin-, adrenocorticotrophic hormone- and luteinising hormone-negative cells that respond mitotically to adrenalectomy. Oestrogen therefore has a previously unrecognised non-cell type-specific trophic effect in the pituitary that obscures the relative expansion of the lactotroph population by inducing concurrent increases in numbers of prolactin-negative cells, the nature of which at least in part remains to be determined. [source]

Prognostic significance of tumor shape and stromal chronic inflammatory infiltration in squamous cell carcinomas of the oral tongue

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2010
Ioulia Chatzistamou
J Oral Pathol Med (2010) 39: 667,671 Background:, Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow-up and status in primary SCCs of the mobile tongue. Methods:, Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow-up and status in patients treated initially by surgery. Results:, Tumor shape was significantly associated with the presence of perineural invasion. Well-defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill-defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well-defined shaped tumors. Conclusion:, Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue. [source]

Liver-targeted doxorubicin: effects on rat regenerating hepatocytes

LIVER INTERNATIONAL, Issue 3 2004
Giuseppina Di Stefano
Abstract: Background/Aims: The conjugate of doxorubicin (DOXO) with lactosaminated human albumin (L-HSA) has the potential of improving DOXO efficacy in the treatment of hepatocellular carcinomas (HCCs) expressing the asialoglycoprotein receptor (ASGP-R). In view of an adjuvant chemotherapy with L-HSA,DOXO after the surgical removal of the tumour, in the present experiments we verified whether DOXO accumulation produced by the conjugate can impair the liver regeneration following hepatic resection in non-cirrhotic liver. Methods: Using saline-injected hepatectomised rats as controls, we studied the effects of the conjugate on the ultrastructure of regenerating hepatocytes and evaluated [3H]thymidine incorporation, mitotic index and rate of DNA recovery in the liver remnant. Results: L-HSA,DOXO caused a selective drug accumulation in liver remnant, with low DOXO levels in extra-hepatic tissues. It did not change the ultrastructure of hepatocytes and did not increase serum alanine aminotransferase. It decreased [3H]thymidine incorporation and mitotic index, causing a moderate delay in hepatic DNA recovery. Conclusions: The experiments indicate a substantial resistance of rat regenerating hepatocytes to high intracellular concentrations of DOXO. They support the possibility of using L-HSA,DOXO in an adjuvant chemotherapy after the surgical removal of HCCs which maintain the ASGP-R. [source]

Cytotoxic and antimitotic effects of N -containing Monascus metabolites studied using immortalized human kidney epithelial cells

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 4-5 2006
Anja Knecht
Abstract Recently the first Monascus metabolites with a pyridine ring were detected, the monascopyridines A and B. They are formally dehydrogenated derivatives of the red rice pigments rubropunctamine and monascorubramine. Because of their structural similarity, the toxicological effects of these secondary metabolites were studied using immortalized human kidney epithelial cells. The cytotoxicity was determined with the following different endpoint detection methods: metabolic activity, trypan blue exclusion, and electronic cell counting. The compounds led to EC50 values between 11 and 31 ,mol/L but the pigments caused a stronger reduction of the cell viability. Also, the apoptotic potential was examined by measuring caspase 3 activity and detecting apoptotic bodies, but none of the tested compounds induced apoptosis. All four substances caused a rise of the mitotic index to about 9% (100 ,mol/L monascopyridine A and B) and 20% (25 ,mol/L rubropunctamine and monascorubramine). The significant decrease of the ratio of cells in the ana- and telophase to cells in the prometa- and metaphase proved a stop of the mitosis at the meta- to anaphase control point. The compounds caused mitotic arrest and the formation of structural damages like c-mitosis through interaction with the mitotic spindle. These effects point to an aneuploidy inducing potential, which is linked to cancer formation. [source]

Platelet-activating factor and human meningiomas

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2006
Y. Denizot
Meningiomas are common primary intracranial tumours. Platelet-activating factor (PAF) is an inflammatory and angiogenic lipid mediator involved in several types of cancer. The presence of PAF receptor (PAF-R) transcripts, the levels of PAF, the phospholipase A2 activity (PLA2, the enzymatic activity implicated in PAF formation) and the PAF acetylhydrolase activity (AHA, the PAF degrading enzyme) were investigated in 49 human meningiomas. PAF-R transcripts, PAF, PLA2 and AHA were detected in meningiomas. However, their levels did not correlate with biological parameters such as the tumour grade, the presence of associated oedema, necrosis, mitotic index as well as intensity of the neovascularization and chronic inflammatory response. In conclusion, PAF is present in meningiomas where it might act on tumour growth by altering the local angiogenic and/or cytokine networks as previously suggested for human breast and colorectal cancer. [source]

Malignant peripheral nerve sheath tumor arising in benign ancient schwannoma: A case report with an immunohistochemical study

PATHOLOGY INTERNATIONAL, Issue 2 2000
Yoshiki Mikami
A rare example of malignant transformation in an ancient schwannoma arisng in the right side of the neck of a 51-year-old man without any clinical manifestations suggesting neurofibromatosis is described. The tumor, approximately 4 cm at its largest dimension, was well circumscribed and had a direct connection with the sympathetic nerve. Microscopically, the central portion of the tumor showed features of ancient schwannoma characterized by extensive hyalinization with cystic degeneration, scattered spindle cells with hyperchromatic and tapered nuclei, and some symplastic changes. However, predominantly in the outer portion, a proliferation of spindle-shaped cells with enlarged nuclei was present. The nuclei of these cells showed irregular contours, coarse granular chromatin texture, and conspicuous nucleoli. Mitotic figures and small necrotic foci with scattered apoptotic bodies were also seen. Immunohistochemically, S-100 protein was almost negative in areas consisting of overtly atypical cells where the mitotic index evaluated with MIB-1 antibody was 30.5%. In contrast, S-100-positive bland spindle cells were scattered in an extensively hyalinized area with a labeling index less than 3%. P53 protein was strongly positive in atypical spindle cells. Although it is a very uncommon event, definite nuclear atypia, frequent mitotic figures, and the existence of small necrotic foci should be recognized as indicating a diagnosis of malignant degeneration of benign schwannoma. Immunohistochemistry would be useful as an ancillary technique in such a setting. [source]

Salt- and glyphosate-induced increase in glyoxalase I activity in cell lines of groundnut (Arachis hypogaea)

PHYSIOLOGIA PLANTARUM, Issue 4 2002
Mukesh Jain
Glyoxalase I (EC 4.4.1.5) activity has long been associated with rapid cell proliferation, but experimental evidence is forthcoming, linking its role to stress tolerance as well. Proliferative callus cultures of groundnut (Arachis hypogaea L. cv. JL24) showed a 3.3-fold increase in glyoxalase I activity during the logarithmic growth phase, correlating well with the data on FW gain and mitotic index. Inhibition of cell division decreased glyoxalase I activity and vice versa, thus further corroborating its role as a cell division marker enzyme. Cell lines of A. hypogaea selected in the presence of high salt (NaCl) and herbicide (glyphosate) concentrations, yielded 4.2- to 4.5-fold and 3.9- to 4.6-fold elevated glyoxalase I activity, respectively, in a dose dependent manner reflective of the level of stress tolerance. The stress-induced increase in enzyme activity was also accompanied by an increase in the glutathione content. Exogenous supplementation of glutathione could partially alleviate the growth inhibition of callus cultures induced by methylglyoxal and d -isoascorbic acid, but failed to recover the loss in glyoxalase I activity due to d -isoascorbic acid. The adaptive significance of elevated glyoxalase I activity in maintaining glutathione homeostasis has been discussed in view of our understanding on the role of glutathione in the integration of cellular processes with plant growth and development under stress conditions. [source]

DNA endoreduplication in maize endosperm cells: the effect of exposure to short-term high temperature

PLANT CELL & ENVIRONMENT, Issue 6 2000
G. Engelen-Eigles
ABSTRACT DNA endoreduplication in Zea mays L. (cv. A619 × W64A) endosperm peaks between 16 and 18 d after pollination (DAP). The physiological function of DNA endoreduplication is not known but it is believed to be important in maize kernel development. In the present study, we investigated how 2, 4 or 6 d of high temperature (35 °C) affected DNA endoreduplication and maize kernel development in comparison with control kernels grown at 25 °C. Data were collected on fresh weight (FW), nuclei number, mitotic index, and DNA endoreduplication. Maize endosperm FW and nuclei number were reduced by exposure to 4 or 6 d of high temperature. At 18 DAP, the 2 d high temperature treatment (HTT) caused a reduction in FW and nuclei number, but had no effect on DNA endoreduplication and average DNA content per endosperm. However, when the exposure to high temperature was increased to 4 or 6 d, FW, nuclei number and the magnitude of DNA endoreduplication were progressively reduced, and the peak mitotic index was delayed compared with the control endosperm. At 18 DAP, the 4 d treatment showed 54·7% of the cells were 3 or 6 C, whereas only 41·2% were 12 C or higher. Six days of high temperature also resulted in a reduction in endosperm FW, nuclei number and a delay in the peak of mitotic index. DNA endoreduplication occurred in the kernels exposed to this treatment, although the magnitude was severely reduced compared with the control kernels. Nuclear DNA content was highly correlated (r= 0·93) with kernel FW, suggesting an important role of DNA endoreduplication in determining endosperm FW. The data suggest that high temperature during endosperm cell division exerted negative effects on DNA endoreduplication by dramatically reducing the nuclei number, leaving fewer nuclei available for DNA endoreduplication. However, the data also suggest that prolonged exposure to high temperature restricts entry of mitotic cells into the endoreduplication phase of the cell cycle. [source]

Origin and evolution of somatic cell testicular tumours in transgenic mice,

THE JOURNAL OF PATHOLOGY, Issue 4 2010
Silvina Quintana
Abstract Transgenic mice bearing a construct in which the expression of the SV40 oncogene is directed by the AMH promoter (AT mice) develop testicular tumours in adult life. We aimed to study early steps of tumour development and characterize tumours at different ages by histological, morphometric, and immunohistochemical techniques. One- to 3-month-old AT mice depicted multifocal Leydig cell hyperplasia. The testicular volume occupied by interstitial tissue was significantly higher in 3-month-old AT mice in comparison with littermate controls. Between 5 1/2 and 7 months, microscopic interstitial tumours developed that progressively evolved to form large confluent areas of high mitotic index in 7- to 14-month-old AT mice. Tumour cells had the characteristics and histoarchitecture of Leydig cells, or formed solid cord-like structures reminiscent of those seen in Sertoli cell tumours. Hyperplastic areas and tumours diffusely expressed 3,-hydroxysteroid dehydrogenase (3,-HSD) in Leydig cell areas. AMH expression was negative in Leydig cell conglomerates and tumours and variable in cord-like tumours. The SV40 T antigen and markers of cell proliferation (PCNA) were intensely positive in hyperplastic cells and tumours. Control mice of similar ages showed neither hyperplasia nor tumours, and SV40 T expression was always negative. In conclusion, transgenic mice develop large testicular tumours that are preceded by interstitial hyperplasia and microtumours. The histological and immunohistochemical phenotype of tumours (Leydig and Sertoli cell differentiation, positive 3,-HSD, and variable AMH) suggests a mixed differentiation of somatic cells of the specialized gonadal stroma. The finding that an oncogene directed by a promoter specifically active in fetal Sertoli cells has given rise to testicular tumours of mixed differentiation is compatible with a common origin of Leydig and Sertoli cells from the specific stroma of the gonadal ridge, as supported by double labelling experiments in fetal mice showing co-localization of the transgene with Sertoli and Leydig cell markers. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Cyclooxygenase-2 expression and connection with tumor recurrence and histopathologic parameters in gastrointestinal stromal tumors

APMIS, Issue 11 2009
HÜSEYIN KEMAL TÜRKÖZ
Tissue cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin synthesis and has been shown to have roles in carcinogenesis and tumor progression. Evaluation of COX-2 overexpression in malignancies has been performed mostly on tumors of epithelial origin, and little is known about its presence in mesenchymal tumors, especially gastrointestinal stromal tumors (GIST). COX-2 has been reported to be widely expressed in GIST and has been suggested as a potential diagnostic marker. We evaluated the overexpression and roles of COX-2 in tumorigenesis in GIST with regard to its relation to prognostic parameters and tumor recurrence. We studied the presence of COX-2 expression immunohistochemically and its relation to clinicopathologic prognostic variables in 41 cases of GIST. COX-2 was overexpressed in 21 (51%) of 41 tumors. The extent of overexpression was greater in tumors that recurred after surgical resection. COX-2 overexpression was also higher in tumors with coagulative necrosis, high mitotic index and an infiltrative pattern of growth. The observation of greater COX-2 expression levels in GIST with unfavorable histopathologic variables is contrary to previous reports and consistent with the reported roles of COX-2 in carcinogenesis of epithelial malignancies. [source]

Cysteine enhances clastogenic activity of dimethylarsinic acid

APPLIED ORGANOMETALLIC CHEMISTRY, Issue 7 2002
Mari Kitamura
Abstract The effects of cysteine on dimethylarsinic acid (DMA)-induced cytotoxicity and chromosomal aberration were studied using Chinese hamster V79 cells. The IC 50 of DMA, i.e. the concentration resulting in a 50% decrease in cell population of viable cells, was 130,µg,ml,1 (0.94 mM), whereas that in the presence of 50,µg,ml,1 (0.28 mM) cysteine was 20,µg,ml,1 (0.14 mM). The mitotic index with co-administration of 50,µg,ml,1 (0.36 mM) DMA and 50,µg,ml,1 cysteine was 1.4 times that with 50,µg,ml,1 DMA alone. Whereas 82% of cells divided twice with 25,µg,ml,1 (0.18 mM) DMA alone, most cells divided only once with co-administration of 25,µg,ml,1 DMA and 50,µg,ml,1 cysteine. These results indicated that the increase in mitotic index by cysteine was due to enhancement of mitotic arrest by DMA. With co-administration of 25,µg,ml,1 DMA and 50,µg,ml,1 cysteine, tetraploidy was 14.3% higher and fivefold by that with 25,µg,ml,1 DMA only. Cysteine at 50,µg,ml,1 enhanced induction of chromosomal aberrant cells by DMA. 100,µg,ml,1 (0.72 mM) DMA induced 91% chromosomal aberrant cells in the presence of cysteine, and 12% in the absence of cysteine. Chromatid breaks and chromatid gaps were the most frequent types of aberration induced by co-administration of DMA and cysteine or DMA alone. Co-administration of DMA and cysteine produced many attenuated chromosomal figures. The attenuated chromosomal figures always had several chromatid gaps and chromatid breaks. Our findings may provide clues to arsenic carcinogenesis in humans. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Evaluation of genotoxic effects in human peripheral blood leukocytes following an acute in vitro exposure to 900 MHz radiofrequency fields

BIOELECTROMAGNETICS, Issue 4 2005
O. Zeni
Abstract Human peripheral blood leukocytes from healthy volunteers have been employed to investigate the induction of genotoxic effects following 2 h exposure to 900 MHz radiofrequency radiation. The GSM signal has been studied at specific absorption rates (SAR) of 0.3 and 1 W/kg. The exposures were carried out in a waveguide system under strictly controlled conditions of both dosimetry and temperature. The same temperature conditions (37.0,±,0.1 °C) were realized in a second waveguide, employed to perform sham exposures. The induction of DNA damage was evaluated in leukocytes by applying the alkaline single cell gel electrophoresis (SCGE)/comet assay, while structural chromosome aberrations and sister chromatid exchanges were evaluated in lymphocytes stimulated with phytohemagglutinin. Alterations in kinetics of cell proliferation were determined by calculating the mitotic index. Positive controls were also provided by using methyl methanesulfonate (MMS) for comet assay and mitomycin-C (MMC), for chromosome aberration, or sister chromatid exchange tests. No statistically significant differences were detected in exposed samples in comparison with sham exposed ones for all the parameters investigated. On the contrary, the positive controls gave a statistically significant increase in DNA damage in all cases, as expected. Thus the results obtained in our experimental conditions do not support the hypothesis that 900 MHz radiofrequency field exposure induces DNA damage in human peripheral blood leukocytes in this range of SAR. Bioelectromagnetics 26:258,265, 2005. © 2005 Wiley-Liss, Inc. [source]

Osteopontin as a molecular prognostic marker for melanoma

CANCER, Issue 1 2008
Javier Rangel MD
Abstract BACKGROUND. Osteopontin has been suggested as a marker of disease progression in patients with melanoma because of its overexpression in recent microarray analyses. However, its prognostic role in melanoma has not been fully defined. METHODS. Osteopontin expression status was examined using immunohistochemical analysis of a tissue microarray that contained primary cutaneous melanomas from 345 patients. The correlation between osteopontin expression and several histologic markers for melanoma was assessed by using the Chi-square test and the Le directional test. The impact of osteopontin expression on recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with melanoma was examined using Cox regression and Kaplan-Meier analyses. The impact of increasing osteopontin expression on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis. RESULTS. High osteopontin expression was associated with increased tumor thickness (P = .037), Clark level (P = .035), and mitotic index (P = .046). Kaplan-Meier analysis demonstrated an association between osteopontin expression and reduced RFS (P < .03) and DSS (P = .05). Multivariate Cox regression analysis demonstrated that high osteopontin immunostaining had an independent impact on the DSS of this melanoma cohort (P = .049). In addition, osteopontin expression was significantly predictive of SLN metastasis (P = .009) and SLN burden, as assessed by the mean number of SLN metastases (P = .0025). Multivariate logistic regression analysis demonstrated an independent role for osteopontin expression in predicting SLN status (P = .0062). CONCLUSIONS. The current results validated the role of osteopontin as an independent prognostic marker for melanoma and provided new evidence for its predictive role in melanoma lymph node metastasis. Cancer 2008. © 2007 American Cancer Society. [source]

G2 -phase radiation response in lymphoblastoid cell lines from Nijmegen breakage syndrome

CELL PROLIFERATION, Issue 2 2002
A. Antoccia
The relationship between G2 -phase checkpoint activation, cytoplasmic cyclin-B1 accumulation and nuclear phosphorylation of p34CDC2 was studied in Nijmegen breakage syndrome cells treated with DNA damaging agents. Experiments were performed on lymphoblastoid cell lines from four Nijmegen breakage syndrome patients with different mutations, as well as on cells from an ataxia telangiectasia patient. Lymphoblastoid cell lines were irradiated with 0.50,2 Gy X-rays and the percentage of G2 -phase accumulated cells was evaluated by means of flow cytometry in samples that were harvested 24 h later. The G2 -checkpoint activation was analysed by scoring the mitotic index at 2 and 4 h after treatment with 0.5 and 1 Gy X-rays and treatment with the DNA double-strand break inducer calicheamicin-,1. Cytoplasmic accumulation of cyclin-B1 was evaluated by means of fluorescence immunostaining or Western blotting, in cells harvested shortly after irradiation with 1 and 2 Gy. The extent of tyrosine 15-phosphorylated p34CDC2 was assessed in the nuclear fractions. Nijmegen breakage syndrome cells showed suboptimal G2 -phase checkpoint activation respect to normal cells and were greatly different from ataxia telangiectasia cells. Increased cytoplasmic cyclin-B1 accumulation was detected by both immunofluorescence and immunoblot in normal as well as in Nijmegen breakage syndrome cells. Furthermore, nuclear p34CDC2. phosphorylation was detected at a higher level in Nijmegen breakage syndrome than in ataxia telangiectasia cells. In conclusion, our data do not suggest that failure to activate checkpoints plays a major role in the radiosensitivity of Nijmegen breakage syndrome cells. [source]

Human red blood cells have an enhancing effect on the relative expansion of CD8+ T lymphocytes in vitro

CELL PROLIFERATION, Issue 6 2001
B. Porto
The present study was designed to analyse the effect of red blood cells on T-cell proliferation and expansion. A comparative study was done in peripheral blood cell cultures stimulated with phytohemagglutinin, with or without red blood cells. The presence of red blood cells had a consistent enhancing effect on T lymphocyte proliferation, as determined by an increase in both the mitotic index and thymidine uptake. Phenotypic characterization of T cell blasts by flow cytometry revealed that, in the presence of red blood cells, expanding cells were preferentially CD8+ cells. Accordingly, proliferation of CD8+ lymphocytes from two patients with CD8+ hyperlymphocytosis was dependent on the presence of red blood cells. In contrast, proliferation of CD4+ lymphocytes from two patients with CD4+ hyperlymphocytosis was strongly inhibited by the presence of red blood cells. This is the first reported evidence that human red blood cells have an enhancing effect on the expansion of CD8+ lymphocytes in vitro. [source]