Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC.

Sarkis, A.; Bajorin, Dean F.; Reuter, Victor E.; Herr, Harry W.; Netto, George J.; Zhang, Zuo‐Feng; Schultz, Paul; Cordon‐Cardo, Carlos; Scher, Howard I.

doi:10.1200/jco.1995.13.6.1384

Cited by 220 publications

(107 citation statements)

References 24 publications

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“…The p53 tumor suppressor gene is one of the most investigated genes in the chemosensitivity of urothelial cancer, but previous findings have been conflicting on whether it is responsible for the resistance to the effects of CDDP-based systemic chemotherapy (Sarkis et al, 1995;Cote et al, 1997). One of the main reasons can be explained by two distinct functions of p53 in response to DNA damage, one of which is cell-cycle arrest, mainly via p21, and the other is the induction of apoptosis via such genes as PUMA and PIG3.…”

Section: Introductionmentioning

confidence: 99%

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

et al. 2008

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To improve conventional chemotherapeutic efficacy, a combination use of traditional medicines is effective but detailed mechanisms have been rarely elucidated. In the this study, we attempted to clarify how triptolide (PG490), an oxygenated diterpene derived from a Chinese herb, enhances the cisplatin (CDDP)-induced cytotoxicity in urothelial cancer cells. Our results showed that a combined CDDP/triptolide therapy induced apoptosis in urothelial cancer cell lines with wild-type p53, but not in those with mutant-type p53 or normal human urothelium. As the mechanism, triptolide suppressed CDDP-induced p53 transcriptional activity, leading to p21 attenuation, which promoted apoptosis via the activation of c-Jun N-terminal kinase (JNK) and Bax. We further demonstrated that the functional regulation of p53 by triptolide was mediated by an intranuclear association of p53 with glycogen synthase kinase-3b (GSK3b), which was inactivated by protein kinase C (PKC). This modulation of the PKC-GSK3b axis by triptolide was observed in a cancer-specific manner. A mouse xenograft model also showed that a combined CDDP/triptolide therapy completely suppressed tumor growth without any side effects. We expect that cancer-specific enhancement of CDDP-induced cytotoxicity with triptolide may effectively overcome the resistance to a CDDP-based conventional chemotherapy as a treatment for urothelial cancer.

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Section: Introductionmentioning

confidence: 99%

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

et al. 2008

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“…For example, it is uncertain whether p53 status is helpful in predicting responses to chemotherapy or surgery. Sarkis et al 43 showed that altered p53 was an independent prognostic marker for survival and an indicator of treatment failure in patients with invasive BC treated with neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) therapy. Conversely, Cote and coworkers 44 found that the only group of patients with local and regionally extensive TCC who benefited from cisplatin-based adjuvant chemotherapy had abnormal p53 expression.…”

Section: Retinoblastoma Tumor Suppressor Genementioning

confidence: 99%

Molecular Mechanisms and Pathways in Bladder Cancer Development and Progression

Jung

Messing

2000

Cancer Control

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Background: The basis for bladder cancer development and progression is complex and involves genetic abnormalities. These abnormalities yield phenotypic changes that allow normal transitional cells to becomeity of these new cases, approximately 75%, are limited to the mucosa (stage Ta or Tis) and lamina propria (T1) at presentation, and most of these tumors can be removed by transurethral resection. Recurrence rates are high (30% to 85%), and 10% to 30% of "superficial" tumors (T1 or less) will subsequently progress to muscle invasive disease (stages T2-T4), which has a poorer prognosis. 2 For the remaining 25%, the initial presentation involves muscle invasive disease that will usually relapse with metastases (as well as localized disease persistence) within a median of 2 years if managed only by transurethral resection and intravesical therapy. 3 These data support the heterogeneous nature and malignant potential of transitional cell carcinoma

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“…In order to follow and further expand these early experiments, and put them into perspective with recent insights into the regulation of proliferation inhibition and generation of apoptosis on the molecular level, we have investigated the induction of these phenomena by a series of retinoids (9-cis-retinoic acid (9cRA), 13-cis-retinoic acid (13cRA), all-trans retinoic acid (tRA)) and IFN-α in various human STS cell lines including HTB-82 (rhabdomyosarcoma), HTB-91 (fibrosarcoma), HTB-92 (liposarcoma), HTB-93 (synovial sarcoma) and HTB-94 (chondrosarcoma) in vitro and put them into context with p53 genotype as well as p53 protein expression. This was of particular interest, as growth arrest and induction of apoptosis resulting from appropiate chemo-and/or radiotherapeutic measures have been demonstrated to be dependent upon the intact function of the p53 gene in various models (Bergh et al, 1995;Elledge et al, 1995;Sarkis et al, 1995). Thus, patients with testicular tumours with regular p53 function have been shown to respond particularly well to chemotherapy (Lutzker and Levine, 1996), whereas patients with malignancies exhibiting high frequency of p53 mutations are known to present often with resistance to chemotherapeutic agents (Aas et al, 1996).…”

mentioning

confidence: 99%

Inhibition of proliferation and induction of apoptosis in soft tissue sarcoma cells by interferon-α and retinoids

Brodowicz¹,

Wiltschke²,

Kandioler-Eckersberger³

et al. 1999

Br J Cancer

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Summary Uncontrolled proliferation and a defect of apoptosis constitute crucial elements in the development and progression of tumours. Among many other biological response modifiers known to influence these mechanisms, the efficacy of retinoids and interferons in the treatment of various malignant entities is currently matter of discussion. In the present study, we have investigated the effects of 9-cis-retinoic acid (9cRA), 13-cis-retinoic acid (13cRA), all-trans-retinoic acid (tRA) and interferon-α on proliferation and apoptosis of human soft tissue sarcoma (STS) cell lines HTB-82 (rhabdomyosarcoma), HTB-91 (fibrosarcoma), HTB-92 (liposarcoma), HTB-93 (synovial sarcoma) and HTB-94 (chondrosarcoma) in relation to p53 genotype as well as p53 expression. HTB-91, HTB-92 and HTB-94 STS cells exhibited mutant p53, whereas wild-type p53 was found in HTB-93 STS cells, and a normal p53 status in HTB-82 STS cells, carrying a silent point mutation only. Interferon-α, irrespective of p53 status, inhibited the proliferation of all five cell lines dose-and time-dependently. Similarly, 9cRA, 13cRA and tRA decreased the proliferation of HTB-82 and HTB-93 STS cells, whereas the proliferation of p53-mutated HTB-91, HTB-92 and HTB-94 STS cells remained unchanged. Furthermore, only 9cRA and tRA were capable of inducing apoptosis in HTB-82 and HTB-93 STS cells, whereas HTB-91, HTB-92 and HTB-94 STS cells did not undergo apoptosis under the influence of 9cRA or tRA. Retinoic acid receptor (RAR)-α and RAR-β mRNA were not detectable by Northern blot analysis in the five STS cell lines, whereas mRNA for the universal retinoic acid receptor, RAR-γ, was expressed in all STS cell lines indicating that retinoid resistance was not associated with a lack of RAR expression. Apoptosis was not induced by interferon-α or 13cRA in any of the five STS cell lines tested. Our results indicate that within the panel of tested STS cell lines, inhibition of proliferation and induction of apoptosis result from different mechanisms which differ in their dependence upon the presence of intact p53.

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Prognostic value of p53 nuclear overexpression in patients with invasive bladder cancer treated with neoadjuvant MVAC.

Abstract: p53 nuclear overexpression has independent prognostic value for survival in patients with invasive bladder cancer treated with neoadjuvant chemotherapy.

Cited by 220 publications

References 24 publications

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3β with p53

Molecular Mechanisms and Pathways in Bladder Cancer Development and Progression

Inhibition of proliferation and induction of apoptosis in soft tissue sarcoma cells by interferon-α and retinoids

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