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Results for “Cell Proliferation”

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PubMed1994

Histopathologic evaluation of proliferating cell nuclear antigen (PC10) in oral epithelial hyperplasias and premalignant lesions.

As the therapeutic options for malignant lesions expand, early accurate diagnosis of premalignancy is becoming increasingly important in the concept of cancer prevention. Because it has been hypothesized that abnormal cell proliferation is related to subsequent malignant transformation, many proliferation markers such as proliferating cell nuclear antigen have been studied in a variety of malignant tumors. In oral surface epithelium, proliferating cell nuclear antigen activity is restricted to basal layers of normal squamous mucosa. In this preliminary study, 169 formalin-fixed, paraffin-embedded oral epithelial lesions, including 28 carcinomas in situ, 82 epithelial dysplasias, 21 epithelial atypia, and 38 typical epithelial hyperplasias, were studied with a monoclonal antibody, PC10, to determine whether proliferating cell nuclear antigen suprabasal expression correlated with premalignancy. The findings revealed that with progression of lesions toward malignancy, there was a significant predilection for basal/suprabasal staining pattern for proliferating cell nuclear antigen as compared with the strictly basal staining pattern seen in normal and benign epithelial conditions. One unexpected staining pattern, suprabasal positive stain only, was also noted mostly in reactive hyperplasia and dysplasia. The data suggested that a positive basal/suprabasal staining pattern for proliferating cell nuclear antigen is indicative of premalignancy in oral epithelial lesions.

Antibodies, Monoclonal↗

PubMed1978

The effect of Rauscher murine leukemia virus infection on the hemopoietic system of BALB/c mice. Cell proliferation and cell loss.

Cell proliferation was investigated in normal and Rauscher Leukemia Virus-infected BALB/c mice. Five days after inoculation, islands of leukemic blasts arose in the red pulp, and proliferated as shown by autoradiographic analysis after a pulse of 3H-Thymidine. These cells subsequently infiltrated the whole spleen and 3 weeks after infection about 60% of the spleen consisted of large immature erythroblast-like cells. Repeated injections of 3H-Thymidine led to uniform labeling of 85% of the spleen cells. Cell cycle analysis showed that for bone marrow as well as for spleen cells the total duration of the cell cycle did not differ from the cell cycle times of normal erythroblasts. From the difference between the actual doubling time and the potential doubling time (estimated on the basis of the cell cycle time) it can be calculated that considerable cell loss must occur. This cell loss is only to a minor extent due to the release of blasts into the peripheral blood. Probably cell death and extrusion of nuclei during erythroid differentiation are the main factors involved.

Animals↗

PubMed2000

Circadian variation of cell proliferation and cell cycle protein expression in man: clinical implications.

Most physiological, biochemical and behavioural processes have been shown to vary in a regular and predictable periodic manner with respect to time. This review focuses on the circadian rhythm in cell proliferation in bone marrow and gut and how this is associated with a circadian expression of cell cycle proteins in human oral mucosa. The control of circadian rhythms by the suprachiasmatic nuclei and the evolving understanding of the genetic and molecular biology of the circadian clock is outlined. Finally, the potential clinical impact of chronobiology in cancer medicine is discussed.

Animals↗

PubMedDate not supplied

Multicompartment analysis of cell proliferation and cell migration in the Sezary syndrome.

Serial radioautographic data obtained in two patients with Sezary syndrome following intravenous tritiated thymidine administration were analysed using multicompartment kinetic models. In both patients, the grain count halving time in the cutaneous Sezary cell compartment was too long to account for the grain count halving rate observed in the peripheral blood. This implies that some proliferating cell compartment other than the skin is primarily responsible for producing the Sezary cells that circulate in the peripheral blood. In both patients, the cell compartment that served as the source of circulating Sezary cells consisted of 5-6 X 10(11) cells (500-600 g of tumor) with an average cell cycle time of 3-4 days. By comparison, the cutaneous Sezary cell compartment was estimated to contain 2.2-4.6 X 10(12) cells (2.2-4.6 kg of tumour) with an average cell cycle time of 7-70 days. While this study does not permit direct anatomic localization of the primary site of Sezary cell production, the properties of this compartment that can be deduced from the available data suggest the lymph nodes as likely candidates. Thus, the Sezary syndrome may well be a true lymph node malignancy with prominent cutaneous manifestations.

Autoradiography↗

PubMed2000

Control of cell proliferation by cell volume alterations in rat C6 glioma cells.

K+ and Cl- channels are involved in regulating the proliferation of a number of cell types. Two main hypotheses have been proposed to explain the mechanism by which these channels influence cell proliferation: regulation of membrane potential and regulation of cell volume. In order to test these hypotheses, we measured, under different experimental conditions, the volume, membrane potential and rate of proliferation of C6 glioma cells. Cells cultured in control medium for 1-4 days were compared with cells cultured for the same period of time in the presence of broad spectrum channel blockers: tetraethylammonium, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and Cs+, in hypertonic media (29% increased osmolarity with NaCl, KCl or sucrose), in hypotonic medium (23% decreased osmolarity with H2O) or in the presence of the specific channel blockers, i.e. mast cell degranulating peptide, charybdotoxin or chlorotoxin. In all of these conditions, we observed a close correspondence between the rate of proliferation and the mean cell volume. The proliferation decreased when volume increased. Moreover, whereas control cells were flattened, spindle-shaped, bipolar or multipolar, cells cultured in media supplemented with NPPB, KCl or CsCl were round with few processes. Of the agents tested, only KCl and Cs+ depolarized the cells. These results show that alterations of the rate of proliferation by K+ and Cl- channel blockers or anisotonia are closely related with changes in cell volume or form but are not correlated with changes in membrane potential.

Animals↗

PubMed1980

Differential changes in cartilage cell proliferation and cell density in the rat craniofacial complex during secondary palate development.

During mammalian secondary palate formation sagittal growth of the lower face has been shown to be more rapid than that of the upper face, and the tongue and mandible extend beneath the primary palate. In order to identify factors contributing to this differential growth pattern, cellular and morphologic growth of the major cartilages of the upper and lower facial regions were studied in radioautographic sections labeled with tritiated thymidine. Evaluation of cell-density recordings, labeling indices, and structural dimensions revealed significant differences between Meckel's cartilage in the lower face, and the nasal cartilage and anterior cranial base cartilage in the upper face. After formation of the precartilaginous blastema, labeling indices were high in Meckel's cartilage (20-30%), but very low in the nasal cartilage and the anterior cranial base (0-2%). During secondary palate formation the volume of Meckel's cartilage increased more rapidly than the other cartilages and its growth was primarily in the sagittal direction. Between days 15 and 17, the increase in the length of Meckel's cartilage (165%) was approximately twice as great as the increase in the combined length of the nasal cartilage and the anterior cranial base (77%). During this period induction of cleft palate with some teratogens has been shown to severely retard growth of Meckel's cartilage and produce mandibular retrognathia that contributes to delayed elevation of the palatal shelves. Therefore, extensive cell proliferation in Meckel's cartilage, during a period of limited proliferation in other craniofacial cartilages, appears to contribute to its rapid growth and its differential sensitivity to growth inhibition.

Animals↗

PubMedDate not supplied

Clinical and prognostic significance of Ki-67 and proliferating cell nuclear antigen expression in childhood primitive neuroectodermal brain tumors.

The cell proliferation activity of sixteen childhood primitive neuroectodermal tumors (PNETs) was observed immunocytochemically, to determine the cell kinetics and cell proliferation activity of these relatively undifferentiated, malignant brain tumors. Two mouse anti-human monoclonal antibodies (MoABs) were employed for the detection of the nuclear antigen (Ki-67) present during proliferation in frozen sections and proliferating cell nuclear antigen (PCNA) expression in formalin fixed, paraffin embedded tissue sections. A sensitive four step, indirect, streptavidin-biotin, alkaline phosphatase (AP) conjugated, immunocytochemical experimental technique, was used. The anti-Ki-67 MoAB which binds to a special nuclear antigen, identified its expression only in proliferating cells. This nuclear antigen was detectable during the whole mitotic cycle of all malignant and fast proliferating cells, only absent between and during phases G0 (resting phase) and the first gap phase (G1). The mean labeling index (MLI) was defined as the percentage of Ki-67 and PCNA antigen positive cells of the total number counted. The MLI for the PNETs ranged between 1.4% and 11.6%, with a mean MLI of 6.2% for Ki-67; and between 3.2% and 16.8%, with a mean of 9.74% for PCNA. All observed PNETs demonstrated heterogeneous nuclear stainings, but the highest MLIs were found among the poorly differentiated classic medulloblastomas (over 30% for the Ki-67 antigen and 46% for PCNA). MLIs were low in 5/13 PNETs (under 4% for antigen Ki-67 and 9.4% for PCNA) and in this group we defined our lowest (1.4%) MLI, suggesting the presence of in vivo neuritogenesis of these undifferentiated, embryonal tumors. MLIs in 6/13 PNETs were intermediate in magnitude. The MLIs were higher in two PNETs with clear cellular differentiation towards an ependymal (10.4%) and melanocytic (8.8%) direction. Formation of astrocytes within the tumor mass did not affect the intermediate character of the MLI (7.8%). The prognosis of every intracranial tumor is obviously correlated with its proliferation activity and cell kinetics. The clinical significance of these parameters is great since they provide direct information concerning the growth characteristics of an intracranial tumor.

Adolescent↗

PubMed2005

Glycosaminoglycans modulate C6 glioma cell adhesion to extracellular matrix components and alter cell proliferation and cell migration.

BACKGROUND: Adhesion to extracellular matrix (ECM) components has been implicated in the proliferative and invasive properties of tumor cells. We investigated the ability of C6 glioma cells to attach to ECM components in vitro and described the regulatory role of glycosaminoglycans (GAGs) on their adhesion to the substrate, proliferation and migration. RESULTS: ECM proteins (type IV collagen, laminin and fibronectin) stimulate rat C6 glioma cell line adhesion in vitro, in a dose-dependent manner. The higher adhesion values were achieved with type IV collagen. Exogenous heparin or chondroitin sulfate impaired, in a dose-dependent manner the attachment of C6 glioma cell line to laminin and fibronectin, but not to type IV collagen. Dextran sulfate did not affect C6 adhesion to any ECM protein analyzed, indicating a specific role of GAGs in mediating glioma adhesion to laminin and fibronectin. GAGs and dextran sulfate did not induce C6 glioma detachment from any tested substrate suggesting specific effect in the initial step of cell adhesion. Furthermore, heparin and chondroitin sulfate impaired C6 cells proliferation on fibronectin, but not on type IV collagen or laminin. In contrast, both GAGs stimulate the glioma migration on laminin without effect on type IV collagen or fibronectin. CONCLUSION: The results suggest that GAGs and proteoglycans regulate glioma cell adhesion to ECM proteins in specific manner leading to cell proliferation or cell migration, according to the ECM composition, thus modulating tumor cell properties.

Animals↗

PubMed2004

The effects of dehydroaltenusin, a novel mammalian DNA polymerase alpha inhibitor, on cell proliferation and cell cycle progression.

As described previously, a natural product isolated from fungus (Acremonium sp.), dehydroaltenusin, is an inhibitor of mammalian DNA polymerase alpha in vitro [Y. Mizushina, S. Kamisuki, T. Mizuno, M. Takemura, H. Asahara, S. Linn, T. Yamaguchi, A. Matsukage, F. Hanaoka, S. Yoshida, M. Saneyoshi, F. Sugawara, K. Sakaguchi, Dehydroaltenusin, a mammalian DNA polymerase alpha inhibitor, J. Biol. Chem. 275 (2000) 33957_33961]. In this study, we investigated the interaction of dehydroaltenusin with lipid bilayers using an in vitro liposome system, which is a model of the cell membrane, and found that approximately 4% of dehydroaltenusin was incorporated into liposomes. We also investigated the influence of dehydroaltenusin on cultured cancer cells. Dehydroaltenusin inhibited the growth of HeLa cells with an LD50 value of 38 microM, and as expected, S phase accumulation in the cell cycle. The total DNA polymerase activity of the extract of incubated cells with dehydroaltenusin was 23% lower than that of nontreated cells. Dehydroaltenusin increased cyclin E and cyclin A levels. In the analysis of the cell cycle using G1/S synchronized cells by employing hydroxyurea, the compound delayed both entry into the S phase and S phase progression. In a similar analysis using G2/M synchronized cells by employing nocodazole, the compound accumulated the cells at G1/S and inhibited entry into the S phase. Thus, the pharmacological abrogation of cell proliferation by dehydroaltenusin may prove to be an effective chemotherapeutic agent against tumors.

Animals↗

PubMed1985

Cell proliferation and cell loss in intramucosal signet ring cell carcinoma of canine stomachs induced by N-ethyl-N'-nitro-N-nitrosoguanidine.

Signet ring cell carcinoma was induced in canine stomachs by N-ethyl-N'-nitro-N-nitrosoguanidine, and modes of cell proliferation and turnover in the carcinoma were studied by 3H-thymidine autoradiography in conjunction with morphometric analysis. From 2 to 15 months after the cessation of 8 months carcinogen treatment, carcinomas in an early stage were obtained. Most of the cancer tissues confined to the lamina propria showed a layered structure. This comprised three layers; the superficial and the deep layer were composed of signet ring cells, and the middle layer was composed of small round cells. The dogs were labeled with 3H-thymidine by s.c. injection and by local infusion of the celiac artery. Flash-labeled autoradiographs revealed that most 3H-thymidine incorporating cancer cells were located around the middle layer, with a small amount of mucin. Using a pulse labeling experiment, those labeled carcinoma cells were shown to migrate from the middle layer towards the surface. Morphometric analysis of the autoradiographs showed that the small cells in the middle layer migrated upwards and produced mucin to become full-blown signet ring cells by 5.5 days. In 15 days, most labeled cancer cells in the superficial layer had disappeared. This mode of cellular turnover appeared to mimic a cell renewal system of the normal gastric mucosa. If the cancer cells turn over in this way, the tumor must grow slowly, remaining as an intramucosal cancer for a relatively long period.

Adenocarcinoma, Mucinous↗

PubMed2004

Chromatin assembly factor-1, a marker of clinical value to distinguish quiescent from proliferating cells.

Histone synthesis and chromatin assembly are mainly associated with DNA replication and are thus intimately involved in cell cycle regulation. The expression of key components involved in these events in human cells was studied in relation to cell-proliferative status. Among several chromatin assembly factors, chromatin assembly factor (CAF)-1 stood out as the most discriminating marker of the proliferative state. We show, using both immunofluorescence and Western blot analysis, that the expression of both CAF-1 large subunits, p150 and p60, is massively down-regulated during quiescence in several cell lines. Upon exit from the quiescent state, the CAF-1 subunits are re-expressed early, before DNA replication. The amounts of either total or chromatin-associated pools of CAF-1 proteins correlate directly with cell proliferation. Regulation of CAF-1 expression is partly controlled at the RNA level, as shown by quantitative reverse transcription-PCR and Northern blot experiments. Biological material from benign and malignant human breast tumors analyzed by immunocytochemistry and immunohistochemistry exhibits a strong positive correlation between CAF-1 p60 expression and the following proliferation markers: S-phase fraction (r = 0.84, P < 0.0001); Ki-67 (r = 0.94, P < 0.0001); and proliferating cell nuclear antigen (r = 0.95, P = 0.0001). We discuss the advantages of using CAF-1 to assess cell proliferation. High CAF-1 p60 levels are also shown to be associated with various prognostic factors. Our data highlight the precise association of CAF-1 expression with the proliferative state and validate the use of this factor as a useful proliferation marker and prognostic indicator in malignant and benign breast lesions.

Biomarkers, Tumor↗

PubMed1996

Association of nm23 protein levels in human prostates with proliferating cell nuclear antigen expression at autopsy.

OBJECTIVE: To investigate nm23-H1 gene expression in the human prostate. METHODS: The nm23-H1 protein levels of normal prostatic tissues, latent cancers of the prostate and primary and metastatic sites of clinical prostate cancers from autopsied men were evaluated using immunohistochemical analysis. Cell proliferation in serial sections using proliferating cell nuclear antigen immunoreactivity was also estimated. RESULTS: Intense nm23-H1 staining was observed in metastatic sites of clinical prostate cancers. The incidence of intense nm23-H1 staining cells in primary sites of clinical prostate cancers was significantly higher than that found in latent cancers and normal prostates (p < 0.01). The staining pattern of nm23-H1 was heterogeneous in latent cancers of the prostate. A significant relationship was observed between nm23-H1 staining and positive proliferating cell nuclear antigen staining (p < 0.01). CONCLUSIONS: These results seem to indicate that the nm23-H1 gene expression is related to cell proliferation and tumor metastatic potential, and appear to show the existence of a biologically different population of cells within the latent cancer.

Aged↗

PubMed2005

Positive correlation of insulin-like growth factor-II with proliferating cell index in patients with colorectal neoplasia.

BACKGROUND: Insulin-like growth factor-II (IGF-II) stimulates cell proliferation and is considered a potential risk factor for colorectal cancer. Tumor levels of IGF-II seem to positively correlate with colorectal cancer cell proliferation. This investigation examined the association of circulating IGF-II to the proliferating cell index (PCI) of tumor and matched normal mucosa in patients with colorectal neoplasia. METHODS: Circulating IGF-II level (ng/mL) was determined in the peripheral blood plasma by ELISA. The proliferating cells in tumor or matched normal mucosa were immunohistochemically stained using the primary antibody against Ki-67. Computer image analysis was used and PCI was expressed as the percentage of Ki-67-positive cells/total counted cells. RESULTS: Sixty-four patients were evaluated; 45 had colorectal neoplasia (27 males/18 females; mean age, 66.8 +/- 11.8 years) and 19 had hyperplastic polyps (6 males and 13 females; mean age, 58.4 +/- 14.4 years). Among patients with colorectal neoplasia, blood IGF-II levels were positively correlated with PCI in the matched normal mucosa (r = 0.46, P < 0.05) but not in the tumor. In patients with hyperplastic polyps, blood IGF-II levels were not correlated with the PCI in the polyps. Blood IGF-II levels were higher in colorectal cancer patients with Dukes' C/D stage (P < 0.01) or with positive lymph nodes (P < 0.01). CONCLUSION: Circulating IGF-II positively correlated with PCI in normal colonic mucosa of patients with colorectal neoplasia, suggesting that IGF-II may have a role in initiating the carcinogenic pathway by stimulating cell proliferation. Blood IGF-II was increased in advanced colorectal cancer, indicating that it might enhance colorectal cancer progression and be a useful marker of poor prognosis.

Aged↗

PubMed1983

Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation.

The production of a mouse monoclonal antibody, Ki-67, is described. The Ki-67 antibody recognized a nuclear antigen present in proliferating cells, but absent in resting cells. Immunostainings with Ki-67 revealed nuclear reactivity in cells of germinal centres of cortical follicles, cortical thymocytes, neck cells of gastrointestinal mucosa, undifferentiated spermatogonia and cells of a number of human cell lines. The Ki-67 antibody did not react with cells known to be in a resting stage, such as lymphocytes, monocytes, parietal cells and Paneth's cells of gastrointestinal mucosa, hepatocytes, renal cells, mature sperm cells, brain cells, etc. Expression of the antigen recognized by Ki-67 could be induced in peripheral blood lymphocytes after stimulation with phytohaemagglutinin, whereas it disappeared from HL-60 cells stimulated with phorbol esters to differentiate into mature macrophages in a resting stage. These findings suggest that Ki-67 is directed against a nuclear antigen associated with cell proliferation. A first series of immunostainings of tumour biopsies indicated that Ki-67 may be a potent tool for easy and quick evaluation of the proportion of proliferating cells in a tumour.

Animals↗

PubMed2000

Predicting Metastatic Risk of Gastrointestinal Stromal Tumors: Role of Cell Proliferation and Cell Cycle Regulatory Proteins.

Gastrointestinal stromal tumors (GIST) are a heterogeneous group of neoplasms whose biologic behavior is difficult to predict. The aim of this study is to evaluate the prognostic value in GIST of some oncoproteins involved in regulation of cell proliferation. Tumor size, mitosis, necrosis, and p53, c-myc, and bcl-2 protein expression of 32 GIST were studied. Proliferative index was assessed with Ki67. The 32 cases were grouped into the following clinical categories: (1) clinically benign (BN) were defined as disease-free survival greater than 3 years (n=10); (2) clinically malignant (MN) in which local recurrence or metastasis occurred regardless of the follow-up time (n=15); and (3) clinically indeterminate (ID) owing to follow-up <3 years without metastasis or local recurrence (n=seven). Discriminant analysis was used to allocate any tumor to one of the two prognostic groups (BN or MN). In univariate analysis all six factors studied above proved to be of significant prognostic value. Using a multivariate stepwise discriminant analysis to take into account the interrelationship between factors, we found that c-myc expression was the most important prognostic factor, followed, in order of statistical weight, by size and Ki67. These were combined to define a discriminant score ([10.75 x c-myc]+[0.39 x size]+[0.078 x Ki67]-15.54=score), which was capable of correctly identifying tumors in our series whose known clinical behavior was BN or MN in 92% of the cases. The classification score was applied subsequently to the seven clinically ID cases: Three (42.9%) were predicted as BN, and four (57.1%) were predicted as MN. Both expression of oncoprotein c-myc and the proliferative index provide prognostic information in GIST, in addition to morphologically established prognostic factors such as size. These factors in a discriminant analysis proved to be useful for the clinical classification of GIST into BN or MN and to predict the clinical outcome of clinically ID tumors. Int J Surg Pathol 8(2):133-144, 2000

Journal Article↗

PubMed2023

Transient Zn2+ deficiency induces replication stress and compromises daughter cell proliferation.

Cells must replicate their genome quickly and accurately, and they require metabolites and cofactors to do so. Ionic zinc (Zn2+) is an essential micronutrient that is required for hundreds of cellular processes, including DNA synthesis and adequate proliferation. Deficiency in this micronutrient impairs DNA synthesis and inhibits proliferation, but the mechanism is unknown. Using fluorescent reporters to track single cells via long-term live-cell imaging, we find that Zn2+ is required at the G1/S transition and during S-phase for timely completion of S-phase. A short pulse of Zn2+ deficiency impairs DNA synthesis and increases markers of replication stress. These markers of replication stress are reversed upon resupply of Zn2+. Finally, we find that if Zn2+ is removed during the mother cell's S-phase, daughter cells enter a transient quiescent state, maintained by sustained expression of p21, which disappears upon reentry into the cell cycle. In summary, short pulses of mild Zn2+ deficiency in S-phase specifically induce replication stress, which causes downstream proliferation impairments in daughter cells.

Biological sciences↗

PubMed2004

The Drosophila wing differentiation factor vestigial-scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc.

Links between genes involved in development, proliferation and apoptosis have been difficult to establish. In the Drosophila wing disc, the vestigial (vg) and the scalloped (sd) gene products dimerize to form a functional transcription factor. Ectopic expression of vg in other imaginal discs induces outgrowth and wing tissue specification. We investigated the role of the VG-SD dimer in proliferation and showed that vg antagonizes the effect of dacapo, the cyclin-cdk inhibitor. Moreover, ectopic vg drives cell cycle progression and in HeLa cultured cells, the VG-SD dimer induces cell proliferation per se. In Drosophila, ectopic vg induces expression of dE2F1 and its targets dRNR2 and string. In addition vg, but not dE2F1, interacts with and induces expression of dihydrofolate reductase (DHFR). Moreover, a decrease in VG or addition of aminopterin, a specific DHFR inhibitor, shift the dorso-ventral boundary cells of the disc to a cell death sensitive state that is correlated with reaper induction and DIAP1 downregulation. This indicates that vg in interaction with dE2F1 and DHFR is a critical player for both cell proliferation and cell survival in the presumptive wing margin area.

Animals↗

PubMed2005

Effects of irradiation and cisplatin on human glioma spheroids: inhibition of cell proliferation and cell migration.

PURPOSE: Investigation of cell migration and proliferation of human glioma cell line spheroids (CLS) and evaluation of morphology, apoptosis, and immunohistochemical expression of MIB-1, p53, and p21 of organotypic muticellular spheroids (OMS) following cisplatin (CDDP) and irradiation (RT). MATERIAL AND METHODS: Spheroids of the GaMg glioma cell line and OMS prepared from biopsy tissue of six glioblastoma patients were used. Radiochemosensitvity (5 microg/ml CDDP followed by RT) was determined using migration and proliferation assays on CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21 expression were examined 24 and 48 h following treatment. RESULTS: Combination treatment led to a migration inhibition of 38% (CDDP 13%; RT 27%) and specific growth delay of 2.6 (CDDP 1.3; RT 2.1) in CLS. Cell cycle analysis after combination treatment showed an accumulation of cells in the G2/M phase. In OMS, apoptosis increased, cell proliferation decreased, and p53/p21 expression increased more pronounced following CDDP+RT. No morphological damage was observed. CONCLUSION: CDDP can lead to enhancement of the RT effect in spheroids of both human glioma cell line spheroids and biopsy spheroids from glioblastoma specimens. The exerted effect is additive rather than synergistic.

Antineoplastic Agents↗