Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma: possible predictors for response to radiochemotherapy and successful bladder preservation

Rödel, Claus; Grabenbauer, Gerhard G.; Rödel, Franz; Birkenhake, S.; Kühn, Reinhard; Martus, Peter; Zörcher, Thomas; Fürsich, Dominik; Papadopoulos, Thomas; Dunst, Jürgen; Schrott, K. M.; Sauer, Rolf

doi:10.1016/s0360-3016(99)00544-1

Cited by 99 publications

(54 citation statements)

References 33 publications

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“…In this series, there was a weak correlation between the Ki-67 index and local control. Other studies that have used Ki-67 as a marker of proliferation in transitional cell bladder cancer have reported a significantly lower progression-free and disease-specific survival rates in patients with higher Ki-67 indices (Popov et al, 1997;Lara et al, 1998;Moonen et al, 1998a;Rodel et al, 2000). Clinical data relating the effect of treatment duration on bladder outcome are equivocal (Maciejewski and Majewski, 1991;De Neve et al, 1995;Moonen et al, 1998b).…”

Section: P=00021mentioning

confidence: 99%

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

et al. 2003

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Glucose transporter-1 protein (GLUT1) and carbonic anhydrase IX (CAIX) are regulated by hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for hypoxia. This study directly compares CAIX and GLUT1 with pimonidazole binding in a prospective series of bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of bladder cancer patients treated in a phase II trial of radical radiotherapy with carbogen and nicotinamide (ARCON). A total of 21 patients with a diagnosis of transitional cell carcinoma of the bladder received 0.5 g m À2 pimonidazole. Serial tumour sections were stained for pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P ¼ 0.0001) for GLUT1 and 0.74 (Po0.0001) for CAIX. In both series of patients, the intrinsic hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The hypoxia markers did not predict for local control or metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both hypoxia modification and accelerated treatment may be valid treatment options in bladder cancer.

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Section: P=00021mentioning

confidence: 99%

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

et al. 2003

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“…Specifically, we suggest that apoptotic threshold proximity, assessed through a clinically determined BAR, has the potential to be explored as an independent variable determining treatment outcome. Previous reports correlating the apoptotic index in cancer biopsies with subsequent response to radiation/chemoradiotherapy in tumors have been inconsistent (8)(9)(10). However, our clinically determined BAR assay (baseline M30 readout in blood normalized by total tumor volume determined by volumetric computed tomography scanning) seems to show very strong correlation with apoptosis induction following SBRT across a range of different cancers including NSCLC (Table 1; Fig.…”

Section: Discussionmentioning

confidence: 65%

“…Although clinically some correlation has been reported between the histologically derived apoptotic index of cancers and subsequent response to radiation/chemoradiotherapy in tumors accessible for pretreatment and posttreatment biopsies/resections, findings have not been consistent (8)(9)(10)(11). Beyond the problems of intratumoral heterogeneity when biopsying, histopathologic estimates of apoptosis and in vitro methods based on detecting cells in the process of apoptosis at any one time point may also significantly underestimate the true BAR.…”

mentioning

confidence: 99%

Preclinical and Clinical Estimates of the Basal Apoptotic Rate of a Cancer Predict the Amount of Apoptosis Induced by Subsequent Proapoptotic Stimuli

Kavanagh

Thorburn

Camidge

2010

Clinical Cancer Research

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Purpose: We hypothesized that the basal apoptotic rate (BAR) of a cancer would predict sensitivity to subsequent proapoptotic stimuli. To explore this, preclinical and clinical BAR assays were developed measuring cumulative apoptotic events through ELISAs for soluble caspase-cleaved cytokeratin 18 (M30) normalized to either cell number increase or total tumor volume, respectively.Experimental Design: The BARs of A549, HCC44, and SW1573 non-small cell lung carcinoma cell lines were measured following different pro/antiapoptotic manipulations. In isogenic wild-type and stable knockdown (KD) series, pretreatment BARs were correlated with response to proapoptotic stimuli and compared with established apoptosis assays. Pretreatment and posttreatment serum was available from stereotactic body radiation therapy patients.Results: Caspase inhibition and p53 KDs reduced the BAR, whereas serum deprivation, XIAP, or Bcl2 KDs increased the BAR. The nontreated BAR rank ordering of the XIAP series recapitulated that with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and caspase-3/7 activity assays, and predicted each line's sensitivity to TRAIL or irradiation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, however, underestimated basal apoptosis during increased apoptotic stress, and caspase-3/7 activity detected minimal death in the media. P53 KDs with lower nontreated BARs were less sensitive to TRAIL and cisplatinum than wild-type. Stereotactic body radiation therapy increased serum M30 values, and the pretreatment clinical BAR strongly correlated with fold change in M30 on treatment (r = 0.93).Conclusions: M30-based BAR assays reflect apoptosis accurately and are more amenable to clinical application than existing apoptosis assays. The pretreatment BAR correlates with cell and/or tumor sensitivity to extrinsic and intrinsic apoptotic pathway stimulation. Prospective clinical exploration is warranted.

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“…Apopotosisinducing factor (AIF) and EndoG promote chromatin fracture. p53 activates pro-apoptotic genes and inactivates anti-apoptotic genes during this process [73]. …”

Section: The Protein P53 Can Trigger Cell Apoptosismentioning

confidence: 99%

The General Information of the Tumor Suppressor Gene p53 and the Protein p53

Sun¹

2015

JCPCR

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This paper talks about the history of the human gene p53 and some important events since it's discovered in 1979. It also shows the detailed structure of the human gene p53 and the protein p53 which is encoded by the gene TP53. The proteins contain three major domain, N-terminal domain, DNA binding domain and C-terminal domain, each contains unique structure and function. Last, it describes the function of the protein p53 and talks about the future direction of the p53 study

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Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma: possible predictors for response to radiochemotherapy and successful bladder preservation

Cited by 99 publications

References 33 publications

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON

Preclinical and Clinical Estimates of the Basal Apoptotic Rate of a Cancer Predict the Amount of Apoptosis Induced by Subsequent Proapoptotic Stimuli

The General Information of the Tumor Suppressor Gene p53 and the Protein p53

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