Showing papers on "Mitotic index published in 1994"
TL;DR: From a wide variety of light microscopic features assessed, the important predictors that emerged, using a variety of data exploratory techniques, were MI, the degree of cytologic atypia, and the presence or absence of coagulative tumor cell necrosis.
Abstract: A recent trend in the classification of uterine smooth muscle neoplasms (USMNs) into clinically benign and clinically malignant groups has been to move from exclusive reliance upon mitotic index (MI) to an approach that incorporates additional histopathologic characteristics. In furtherance of this goal, we assessed a variety of histopathologic features of 213 problematic smooth muscle neoplasms for which we had > or = 2 years of clinical follow-up data or for which there was an unfavorable outcome. One hundred and thirteen of these patients have had a minimum follow-up of 5 years, and 48 have been followed for > or = 10 years. Cases eliminated from the study group included USMNs with a significant myxoid or epithelioid component and cases of intravenous leiomyomatosis. USMNs, whether cellular or not, with no cytologic atypia and with a mitotic index (MI = number of mitotic figures [mf]/10 high-power fields [hpf]) of or = 10 mf/10 hpf, four of 10 failed.(ABSTRACT TRUNCATED AT 400 WORDS)
663 citations
Journal Article•
TL;DR: Observations demonstrate that p53 function is essential for a major component of the normal response to gamma-irradiation induced DNA damage in intestinal mucosal cells, and suggest that p 53 deficiency permits a population of cells bearing DNA damage to escape the normal process of deletion.
Abstract: p53 is now well characterized as a tumour suppressor gene, with loss of normal p53 function being recorded as the commonest genetic event associated with human malignancy. In particular, its involvement with tumorigenesis within the intestine is well established. Normal p53 function has been shown to be crucial for the induction of apoptosis in tumour cell lines, murine thymocytes and murine haematopoietic cells following DNA damage. To elucidate further the role of p53 in the cellular response to DNA damage we have investigated the response to gamma-irradiation of crypt cells in vivo from the small and large intestine of mice bearing a constitutive p53 deletion. Four hours after gamma-irradiation, a time point at which wild type crypt cells show abundant apoptosis, crypt cells from p53-deficient mice differed in that they were completely resistant to the induction of apoptosis. The p53 dose dependence of this phenomenon was clearly shown by the intermediate level of apoptosis observed in p53 heterozygotes. Analysis of the mitotic index and the bromodeoxyuridine labelling index showed that two other responses of wild type crypts to gamma-irradiation, namely the G2 block and the reduction in bromodeoxyuridine incorporation, were both largely intact in p53 deficient animals. These observations demonstrate that p53 function is essential for a major component of the normal response to gamma-irradiation induced DNA damage in intestinal mucosal cells, and suggest that p53 deficiency permits a population of cells bearing DNA damage to escape the normal process of deletion.
278 citations
TL;DR: Apoptotic cells were quantitated by light microscopy in a series of 288 breast carcinomas, and their number (cells/mm2 of neoplastic epithelium, i.e., the apoptotic index, AI) was related to various histopathological features and disease outcome.
201 citations
TL;DR: The correlation of Ki-67 antigen expression with mitotic figure content was strong enough to suggest that a very carefully measured MFI provides an estimate of tumor growth fraction equivalent to the K67LI, however, which method is optimal for estimating tumor proliferation rate remains unclear.
183 citations
TL;DR: It is concluded that in clinical cell kinetic studies staining for PCNA may serve as an attractive alternative to the BrdU incorporation assay.
Abstract: Immunohistochemistry of the S phase related proliferating cell nuclear antigen (PCNA) was studied as an alternative to ex-vivo bromodeoxyuridine (BrdU) immunohistochemistry for assessment of human colonic cell proliferation. From 16 subjects without colonic disease biopsy specimens were collected from five different sites along the colorectum and processed for BrdU and PCNA immunohistochemistry. The mean proliferation index of PCNA was significantly higher at 133% of the value obtained with BrdU. There was, however, a good correlation between the results from both techniques (r = 0.6275; p < 0.05). Decrease in proliferation index along the colorectum was seen with both staining methods but was clearer with PCNA immunohistochemistry (caecum/ascending colon v rectum: 12.0 v 7.2; p < 0.004). The total number of crypt cells also decreased from proximal to distal (134 to 128; p < 0.06) but at no site correlated significantly with the proliferation index. It is concluded that in clinical cell kinetic studies staining for PCNA may serve as an attractive alternative to the BrdU incorporation assay.
169 citations
TL;DR: The effects of administration of the microenvironment-derived hematopoietic growth factor interleukin-11 (IL-11) on mice given combination radiation/chemotherapy led to significantly increased survival and evidence of rapid recovery of the small intestinal mucosa, which is severely damaged by these cytoxic agents.
162 citations
TL;DR: The results show that AI is related particularly to mitotic activity in transitional cell bladder tumours, while AI as assessed by light microscopy hardly has any independent prognostic significance.
Abstract: Four hundred cases of transitional cell bladder cancer were reviewed by light microscopy for the presence of apoptotic cells in the primary tumour biopsy specimens. The number of apoptotic cells/mm2 of neoplastic epithelium (apoptotic index, AI) was related to various histological features and prognosis. AI was related significantly to high T-category, high grade, DNA aneuploidy, large nuclear morphometric variable values, and high proliferation rate of cancer cells. Tumours showing overexpression of p53 oncoprotein in over 10 per cent of the nuclei had significantly higher AI values than p53-negative tumours. Multivariate regression analysis showed that AI was independently predicted by mitotic index, mean nuclear area, and papillary status. Progression, recurrence-free survival, and survival of superficial tumours were all related significantly to AI. In multivariate survival analysis, T-category, papillary status, grade, and mitotic index had independent prognostic value, while the recurrence-free survival of Ta-T1 tumours was related independently to AI. The results show that AI is related particularly to mitotic activity in transitional cell bladder tumours, while AI as assessed by light microscopy hardly has any independent prognostic significance.
141 citations
TL;DR: The results indicate that entry into and exit out of mitosis are prerequisites for paclitaxel cytotoxicity and show that high concentrations of Cremophor EL are capable of inducing a cell cycle block distinct from the mitotic block seen with pac litaxel.
Abstract: We have perfomed DNA flow analysis, mitotic index studies, time-lapse photography, and paclitaxel uptake studies of human tumor cell lines exposed to paclitaxel. DNA flow analysis demonstrated that cells began accumulating in G2/M within 6 hrs of exposure to paclitaxel; by 12 hrs over 50% of cells accumulated in G2/M at all concentrations tested. After 24 hrs of exposure to 10 nM paclitaxel, cells underwent non-uniform mitotic division resulting in multinucleated cells. Of cells treated with 30 nM to 1000 nM paclitaxel, 75% to 85% remained blocked in G2/M for up to 72 hrs. Although a large proportion of cells treated with higher concentrations of paclitaxel (10,000 nM) was blocked in G2/M, a significant proportion (10% to 40%) of these cells was also in Gl. Cells exposed to lower concentrations of paclitaxel (10 nM to 1000 nM) in medium containing 0.135% (v/v) Cremophor EL also had a relatively large proportion in Gl. Mitotic index studies demonstrated that the paclitaxel-induced G2/M block was initially a mitotic block and that cells remained in mitosis for up to 24 hrs. With additional time of exposure to paclitaxel, mitotic index and time-lapse studies indicated that cells attempted to complete mitosis; however, cytokinesis was inhibited and cells became multinucleated. Time-lapse photography revealed that paclitaxel markedly prolonged the time in mitosis from 0.5 hr to 15 hr. High levels of Cremophor EL (0.135% v/v) markedly reduced the number of cells in mitosis but did not alter the mitotic delay induced by paclitaxel.3H-paclitaxel uptake studies revealed that high concentrations of Cremophor EL did reduce the rate of uptake of paclitaxel into cells but had little effect on total paclitaxel accumulation. These results confirm that paclitaxel has striking effects on the cell cycle and show that high concentrations of Cremophor EL are capable of inducing a cell cycle block distinct from the mitotic block seen with paclitaxel. These results also demonstrate that cells exposed to paclitaxel for longer than 24 hours attempt to complete mitosis but the process of cytokinesis is inhibited. Together with cytotoxicity data, these results indicate that entry into and exit out of mitosis are prerequisites for paclitaxel cytotoxicity.
105 citations
TL;DR: The clinical prognosis given for splenic sarcomas should be modified according to the mitotic index as a predictive value for patient survival, suggesting either ambiguous morphologic findings or the possibility of a common histogenesis from smooth muscle trabeculae or a distinct population of splenic myofibroblasts.
Abstract: Surgical submissions from canine splenectomy cases spanning a 3-year period (1988-1990) were evaluated. Eighty seven neoplasms of the spleen considered to be of nonangiomatous and nonlymphomatous origin were selected for morphologic classification, mitotic index determination, immunohistochemical analysis, and patient survival determination. In 76/87 cases, patient survival information was available, and the mitotic index was determined in 83/87 cases. Immunohistochemistry for selected antigens (vimentin, desmin, smooth muscle actin, myosin, and factor VIII-related antigen) was performed in 58/87 of the cases. Morphologic classification of these lesions in standard HE preparations yielded the following neoplastic groups: fibrosarcoma (19/87), undifferentiated sarcoma (19/87), leiomyosarcoma (14/87), osteosarcoma (8/87), mesenchymoma (7/87), myxosarcoma (6/87), histiocytic sarcoma (6/87), leiomyoma (3/87), lipoma-myelolipoma (2/87), liposarcoma (2/87), and malignant fibrous histiocytoma (1/87). A lack of distinct morphologic characteristics among many of the neoplasms that were classified as either fibrosarcoma, leiomyosarcoma, or undifferentiated sarcoma contrasted these groups with the relatively unambiguous features that distinguished the other sarcoma groups. Using immunohistochemical staining for muscle-specific antigens (desmin, smooth muscle actin, and myosin), specific staining often overlapped extensively within the neoplastic groups of fibrosarcomas, leiomyosarcomas, and undifferentiated sarcomas, suggesting either ambiguous morphologic findings or the possibility of a common histogenesis from smooth muscle trabeculae or a distinct population of splenic myofibroblasts. The biological behavior of all tumors examined could be placed into three categories of patient survival: (1) benign, noninvasive tumors (leiomyoma, lipoma) with prolonged survival intervals; (2) malignant tumors (fibrosarcoma, undifferentiated sarcoma, leiomyosarcoma, osteosarcoma, myxosarcoma, histiocytic sarcoma, and liposarcoma), showing severely truncated survival (median 4 months with 80-100% mortality after 12 months; and (3) intermediate survival periods (median 12 months with 50% 1 year survival) attributed to a single group of neoplasm, the mesenchymomas. The biological behavior of primary splenic nonangiomatous, nonlymphomatous sarcomas was most closely correlated with observed mitotic index. Splenic neoplasms of this type with a mitotic index 9. With the exception of osteosarcoma, all anatomically defined tumor groups contained one or more specimens with a mitotic index < 9. The clinical prognosis given for splenic sarcomas should be modified according to the mitotic index as a predictive value for patient survival.
101 citations
TL;DR: This is the first report to show that apigenin inhibited the proliferation of malignant tumor cells by G2-M arrest and induced morphological differentiation in B104 cells.
100 citations
Journal Article•
TL;DR: P53-deficient hepatoma cells transfected with mutant p53-249ser (codon 249 Arg-->Ser) acquire a new phenotype with an increased in vitro survival and mitotic activity, however, such a phenotypic change is not sufficient to cause a major shift in the poor tumorigenic potential of these cells.
Abstract: Mutations affecting the p53 gene abrogate its tumor suppressor activity. It is, however, unclear whether such mutations can generate mutant p53 proteins with an intrinsic transforming ability. More importantly, the mechanism(s) by which they exert such activity is unknown. We report here that p53-deficient hepatoma cells (Hep3B) transfected with mutant p53-249ser (codon 249 Arg-->Ser) acquire a new phenotype with an increased in vitro survival and mitotic activity. However, such a phenotypic change is not sufficient to cause a major shift in the poor tumorigenic potential of these cells. This is apparently due to transforming growth factor beta 1-mediated apoptotic death of Hep3B cells which is not affected by the expression of p53-249ser.
TL;DR: The results suggest that host alpha-linolenic acid has a specific role in the metastatic process in vivo, and further understanding of the biology of this essential fatty acid of the n-3 series is needed in breast carcinoma.
Abstract: The association between the levels of various fatty acids in adipose breast tissue and the emergence of visceral metastases was prospectively studied in a cohort of 121 patients with an initially localised breast cancer. Adipose breast tissue was obtained at the time of initial surgery, and its fatty acid content analysed by capillary gas chromatography. A low level of alpha-linolenic acid (18:3n-3) in adipose breast tissue was associated with positive axillary lymph node status and with the presence of vascular invasion, but not with tumour size or mitotic index. After an average 31 months of follow-up, 21 patients developed metastases. Large tumour size, high mitotic index, presence of vascular invasion and low level of 18:3n-3 were single factors significantly associated with an increased risk of metastasis. A Cox proportional hazard regression model was used to identify prognostic factors. Low 18:3n-3 level and large tumour size were the two factors predictive of metastases. These results suggest that host alpha-linolenic acid has a specific role in the metastatic process in vivo. Further understanding of the biology of this essential fatty acid of the n-3 series is needed in breast carcinoma.
TL;DR: This study supports the use of surgical staging of patients with uterine sarcomas in order to optimally determine their chance for survival and suggests that DNA index also had prognostic value.
TL;DR: In both mitotic and interphase cells, colcemid-induced apoptosis occurred after a period of cell cycle stasis during which cells failed to complete an initiated cell cycle.
TL;DR: The rate of root growth and mitotic index decreased progressively with increasing cadmium concentration and treatment duration, which could cause mitotic irregularities comprising c-mitoses, anaphase bridges, breaks, stickiness, lagging and vagrant chromosomes and micronuclei.
Abstract: The effects of cadmium at different concentrations (0.5–20 ppm) on root growth, cell division and chromosomal morphology of Hordeum vulgare were studied. The rate of root growth and mitotic index decreased progressively with increasing cadmium concentration and treatment duration. Different concentrations of cadmium could cause mitotic irregularities comprising c-mitoses, anaphase bridges, breaks, stickiness, lagging and vagrant chromosomes and micronuclei. The intensity of the toxic effects is basically dependent on the cadmium concentration and duration of treatment.
TL;DR: The most prevalent abnormality observed in this study was endomitotic reduplication of chromosomes which, along with mitotic inhibition and micronucleus induction, indicated microtubular/mitotic spindle poisoning by deltamethrin, and the increased frequency of chromosome aberrations andmicronucleated erythrocytes in the bone marrow suggests a clastogenic potential of deltAMethrin.
Abstract: Deltamethrin, a synthetic pyrethroid insecticide, was administered to adult female albino rats as a single i.p., s.c., or oral dose of 5.6, 8.4, or 11.2 mg/kg b.w. or repeated i.p. doses of 2.24 mg/kg b.w. for five consecutive days (cumulative dose 11.2 mg/kg b.w.). This treatment inhibited the mitotic index in a dose-dependent manner and increased the frequency of chromosome aberrations in the bone marrow at 24 h post exposure. The parenterally (i.p. and s.c.) administered deltamethrin appeared more effective than the oral gavage for eliciting its cytotoxicity and genetic toxicity potential. The frequency of micronucleated erythrocytes in the bone marrow was also increased at 30 h following a single i.p. dose of 5.6, 8.4, or 11.2 mg/kg b.w. The most prevalent abnormality observed in this study was endomitotic reduplication of chromosomes which, along with mitotic inhibition and micronucleus induction, indicated microtubular/mitotic spindle poisoning by deltamethrin. The increased frequency of chromosome aberrations and micronucleated erythrocytes also suggests a clastogenic potential of deltamethrin. These observations indicate the in vivo susceptibility of mammals to the genetic toxicity potential of deltamethrin.
TL;DR: It was concluded that chenodeoxycholic acid stimulated the development of ACF and altered cell cycle associated events in colonic crypts undergoing neoplastic changes.
TL;DR: There is a G2 checkpoint defect in addition to the well-known defects in S phase and at the G1-S phase transition and a suggestion of an increase in breaks in heterozygotes, but a much larger study would be required to confirm or refute this.
Abstract: The extent of cell cycle delay of lymphocytes X-irradiated in G2 phase was measured by mitotic inhibition determinations in 66 controls, 14 ataxia-telangiectasia (A-T) homozygotes and 27 obligate heterozygotes. Homozygotes had a significantly reduced mitotic index (MI) in unirradiated samples and showed significantly less radiation-induced mitotic inhibition than controls. This confirms our earlier disputed observations on A-T fibroblasts and demonstrates a G2 check-point defect in addition to the well-known defects in S phase and at the G1-S phase transition. There are two separate and opposite abnormal G2 responses of A-T cells; a primary event in which cells in G2 at the time of irradiation suffer less delay than controls, and a secondary event in which cells irradiated at earlier stages of the cycle are more delayed when they pass into G2. The MI of unirradiated heterozygote cells and the extent of mitotic inhibition were indistinguishable from controls. Spontaneous unstable chromosome aberrations were, as previously reported, significantly higher in homozygotes than in controls. This was true for breaks, but not for gaps. There was a suggestion of an increase in breaks in heterozygotes, but a much larger study would be required to confirm or refute this.
TL;DR: No genotoxic effects and increased MI were found in exposed samples compared to the control ones, in agreement with the previous results.
Abstract: We expose human peripheral blood lymphocytes cultures to 50 Hz pulsed magnetic fields (PMFs) in order to evaluate a possible genotoxic effect of such non-ionizing radiation. The genotoxic effect was evaluated in terms of both micronucleus (MN) induction and classical chromosomal aberration (CA); the mitotic index (MI) was also calculated. Khalil and Qassem (1991)_found chromosomal and chromatid breaks and mitotic delay in human lymphocytes exposed for 24, 48 and 72 h to a field with characteristics similar to those used in our laboratory. These data are in contrast with our results previously reported in terms of MN induction using the cytokinesis block method (Scarfi et al., 1991). In this study lymphocytes from five healthy human donors were examined with the above mentioned tests. No genotoxic effects and increased MI were found in exposed samples compared to the control ones, in agreement with our previous results.
TL;DR: In this article, a single dose (60 mg/kg) of cocaine was administered to male albino Swiss mice for 5 days before liver injury, and the results indicated that a significant percentage of cell death induced by cocaine occurs by means of the apoptosis death program.
TL;DR: It is concluded that BCL-2 might contribute to the malignant phenotype of breast cancer by modulation of biological behaviour of cancer cells.
Journal Article•
TL;DR: It is suggested that one initial event during the androgen-independent prostatic tumor regrowth in the PAP relapse model might be a reduction of the number of tumor cells being depleted by apoptosis, rather than an increase of cell proliferation rate.
Abstract: Castration of rats transplanted with the androgen-sensitive Dunning R3327-PAP prostatic tumor results initially in a reduction of tumor growth, but after some time, some of the tumors start to grow again. The relapsed, androgen-insensitive PAP tumor shows a dedifferentiated morphology. In the present study, we examined whether this androgen-independent tumor regrowth was due to an increased cell proliferation rate or to a reduction of the number of tumor cells dying by apoptosis. Nine rats (with 18 tumors) were castrated and followed for 16 to 20 weeks. Six of the tumors increased their volume markedly (relapsed), while 12 remained relatively stable (nonrelapsed). The mitotic index and apoptotic index for epithelial cells were examined by light microscopy. Tumor growth rate correlated negatively both to the apoptotic index identified by morphological criteria ( RS = -0.82; P < 0.0001) and to the apoptotic index identified by in situ end labeling ( RS = -0.83; P < 0.0001). The tumor growth rate percentage did not correlate to the mitotic index, and it was negatively correlated ( RS = -0.62; P < 0.01) to the number of cells immunostained for proliferating cell nuclear antigen. It is suggested that one initial event during the androgen-independent prostatic tumor regrowth in the PAP relapse model might be a reduction of the number of tumor cells being depleted by apoptosis, rather than an increase of cell proliferation rate.
TL;DR: None of the parameters considered revealed a significant difference in proliferative activity of the three types of tumour, but in both seminomas and Sertoli cell tumours the progression from tubular to diffuse pattern paralleled an increase in growth fraction.
Journal Article•
TL;DR: Data show that after intraportal islet islet transplantation the proliferative activity and at the same time the apoptotic elimination of hepatocytes are significantly increased focally in the long-term hyperinsulinemic liver acini.
TL;DR: The effect of various doses (75-300 mg/kg b.w.) of carboplatin on the induction of micronuclei in Ehrlich ascites tumor (EAT) cells was studied and resulted in a dose-dependent increase in the frequency of micronsucleated EAT cells.
Abstract: The effect of various doses (75–300 mg/kg b.w.) of carboplatin on the induction of micronuclei in Ehrlich ascites tumor (EAT) cells was studied. Carboplatin treatment resulted in a dose-dependent increase in the frequency of micronucleated EAT cells. Carboplatin treatment also decreased the mitotic index. The dose-effect curves were linear-quadratic for all the parameters studied. The maximal effect of the drug was obtained in all the treatments after 48 h.
Journal Article•
TL;DR: It is suggested that EGF treatment significantly increases small and large bowel mitogenicity in acutely radiated animals, and EGF significantly decrease the acute clinical manifestations of radiation enteritis.
TL;DR: It is concluded that the immunohistochem‐ical detection of nuclear p53 protein accumulation is highly associated with p53 gene mutations in archival paraffin‐embedded tissues, and that this method is useful for rapid screening of p53 abnormalities.
Abstract: Fifty invasive ductal carcinomas of the breast were analyzed by immunohistochemistry, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing after microdissection of conventional formalin-fixed, paraffin-embedded tissues. A highly significant association between the presence of p53 gene mutation and nuclear accumulation of p53 protein was found (P < 0.0001). Of 13 tumors that demonstrated p53 gene mutations, 11 (84.6%) showed nuclear accumulation of p53 protein. However, of 37 tumors in which gene mutations were not detected, only 5 (13.5%) showed nuclear accumulation of p53 protein. There was a statistically significant association between the nuclear accumulation of p53 protein and a higher histological grade (P < 0.001) or mitotic index (P < 0.01). In addition, gene mutations had a statistically significant association with a higher histological grade (P < 0.05) or mitotic index (P < 0.0001). Therefore, p53 abnormalities might be associated with an aggressive phenotype in breast cancer. We conclude that the immunohistochemical detection of nuclear p53 protein accumulation is highly associated with p53 gene mutations in archival paraffin-embedded tissues, and that this method is useful for rapid screening of p53 abnormalities.
TL;DR: It was observed that the frequency of micronucleated polychromatic erythrocytes (MPCE) increased with the increase in exposure dose at all the post-irradiation time periods studied and the dose-response relationship was linear-quadratic for both MPCE and MNCE.
Abstract: The incidence of micronucleus formation was studied at 12, 24 and 36 h post-irradiation in the polychromatic (PCE) and normochromatic (NCE) erythrocytes of the bone marrow of mice whole-body exposed to 0, 3, 9, 18, 36, 54 and 72 cGy of 60 Co γ-radiation. It was observed that the frequency of micronucleated polychromatic erythrocytes (MPCE) increased with the increase in exposure dose at all the post-irradiation time periods studied. Similarly, the frequency of micronucleated normochromatic erythrocytes (MNCE) also increased with the increase in exposure dose and the increase for both MPCE and MNCE was dose related. The dose-response relationship was linear-quadratic for both MPCE and MNCE. The study of mitotic index revealed that a dose as low as 9 cGy is capable of reducing the mitotic index significantly at 24 h post-irradiation and the dose response was linear-quadratic. However, no significant decline in the mitotic index was observed at 12 and 36 h post-irradiation.
TL;DR: It is suggested that PCNA immunoreactivity is useful in discriminating between neoplastic and non‐neoplastic mesothelium and that it may have prognostic value in malignant Mesothelioma.
Abstract: In order to assess its discriminating and prognostic value, we studied immunoreactivity for proliferating nuclear cell antigen (PCNA) in human malignant mesothelioma (31 cases) and in human non-neoplastic mesothelium (33 cases with reactive mesothelium and 20 cases of normal mesothelium) using the murine monoclonal antibody PC10. We also compared it with mitosis counts expressed as the mitotic volume index (MV index). There were differences between malignant mesothelioma, reactive mesothelium, and normal mesothelium for percentage of PCNA immunoreactive cells (mean +/- SD; 27 +/- 9, 9.5 +/- 5.1, and 3.6 +/- 1.6, respectively) and for their MV index (20.3 +/- 4.5, 9.4 +/- 2.1, and 3.6 +/- 0.6, respectively). The median actuarial survival was 10.1 months for patients with less than 25 per cent PCNA immunoreactive cells, 9.4 months for patients with less than 20 mitoses per mm2 of tumoural tissue, 5.9 months for patients with more than 25 per cent PCNA immunoreactive cells, and 5.3 months for patients with more than 20 mitoses per mm2 of tumoural tissue. Our results suggest that PCNA immunoreactivity is useful in discriminating between neoplastic and non-neoplastic mesothelium and that it may have prognostic value in malignant mesothelioma.
TL;DR: It is shown that complex changes in the cell cycle traverse accompany, but do not precede, the acquisition of the monocytic phenotype by HL60 cells, and the best cell cycle predictor of differentiation potency was the extent of accumulation of the cells in the G2 compartment.
Abstract: . Differentiation of mammalian cells is accompanied by reduced rates of proliferation and an exit from the cell cycle. Human leukemic cells HL60 present a widely used model of neoplastic cell differentiation, and acquire the monocytic phenotype when exposed to analogs of vitamin D3 (VD3). The maturation process is accompanied by two blocks in the cell cycle: an arrest in the G1/G0 phase, and a recently described G2+ M block. In this study we have analyzed the traverse of the cell cycle phases of the well-differentiating HL60-G cells exposed to one of ten analogs of VD3, and compared the cell cycle effects of each compound with its potency as a differentiation-inducing agent. We found that in general there was a good correlation between the effects of these compounds on the cell cycle and on differentiation, but the best cell cycle predictor of differentiation potency was the extent of accumulation of the cells in the G2 compartment. All analogs induced a marked decrease in the mitotic index, and polynucleation of HL60 cells was produced, especially by compounds which were effective as inducers of differentiation. Time course studies showed that induction of differentiation was accompanied by a transient increase of the proportion of cells in the G2+ M compartment, but preceded the G1 to S, and the G2 compartment blocks. These studies indicate that complex changes in the cell cycle traverse accompany, but do not precede, the acquisition of the monocytic phenotype by HL60 cells.