Co-expression of p53 and bcl-2 may correlate to the presence of Epstein–Barr virus genome and the expression of proliferating cell nuclear antigen in nasopharyngeal carcinoma

Niemhom, S; Kitazawa, Sohei; Murao, Shinichi; Kunachak, Somyos; Maeda, Sakan

doi:10.1016/s0304-3835(00)00582-6

Cited by 32 publications

(23 citation statements)

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“…The postoperative clinical outcome was favorable and the patient was recurrence-free 15 mo after resection. This case, to the best of our knowl-with p53 over expression in the nuclei of EBV-infected tumor cells [14] and hyperreactivity of tumor cells for bcl-2 and proliferating cell nuclear antigen (PCNA) [15] . Although it has been suggested by many authors that lymphoepithelioma-like carcinomas have a better prognosis than conventional carcinomas with a less marked lymphocytic infiltrate [10] , given the few studies on the clinical course of lymphoepithelioma-like carcinomas in the literature to date, this topic needs further investigation.…”

Section: Introductionmentioning

confidence: 83%

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

Nemolato

Fanni²,

Naccarato³

et al. 2008

WJG

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Section: Introductionmentioning

confidence: 83%

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

Nemolato

Fanni²,

Naccarato³

et al. 2008

WJG

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“…1,3,5,7,8,11,12,16 It appears that abnormalities of p53 regulation are crucial in development of the lymphoepithelioma-like carcinoma of the urinary tract. 8,[17][18][19] Only a few relatively large series of lymphoepithelioma-like carcinoma have been reported in the urinary bladder. 1,3,[7][8][9]11,12 In the current study, we had 17 pure and 13 mixed lymphoepitheliomalike carcinoma cases.…”

Section: Discussionmentioning

confidence: 99%

Lymphoepithelioma-like carcinoma of the urinary tract: a clinicopathological study of 30 pure and mixed cases

et al. 2007

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We studied 28 cases of lymphoepithelioma-like carcinoma of the bladder, one case in the renal pelvis, and one in the urethra. The mean age of the patients was 67.6 years with 21 (70%) males. Seventeen cases (56.7%) were pure with the remaining mixed with other patterns of carcinoma, including invasive urothelial carcinoma (n ¼ 10), invasive adenocarcinoma (n ¼ 3), and squamous cell carcinoma (n ¼ 2). The surface demonstrated carcinoma in situ (CIS) in six cases, noninvasive high-grade papillary urothelial carcinoma in three cases, and in situ adenocarcinoma in one case. In 19/30 (66%) cases, there was a heavy lymphocytic infiltrate and in the remaining 11/30 (34%) cases a mixed inflammatory infiltrate. None of the 26 cases labeled for EBV-encoded RNA by in situ hybridization. Tumor stages at presentation were: seven cases T1 (23%); 14 cases T2 (47%); seven cases T3 (23%); and two cases T4 (7%). Treatment consisted of radical cystectomy in 13/30 cases (43%); partial cystectomy in 4/30 cases (13%); nephrectomy in one case (3%), and transurethral resection often followed by radiation or chemotherapy in 12/30 (40%) cases. The mean follow up for patients without progression was 31 months. Eight of 27 cases with follow-up (30%) cases had tumor recurrence, with seven patients having metastases. In cases treated with cystectomy, the 5-year actuarial recurrence-free risk was 59% (62 and 57%, for pure and mixed cases, respectively). Lymphoepithelioma-like carcinoma, whether in pure or mixed form, has a similar prognosis to ordinary urothelial carcinoma when treated by cystectomy. Of the three pure cases treated by chemotherapy, two were free of disease at 4 and 65 months and the third had recurrent disease at 17 months. Given the association of lymphoepithelioma-like carcinoma with urothelial carcinoma in 47% of our cases and its propensity for multifocality, partial cystectomy would typically be ill advised for lymphoepithelioma-like carcinoma.

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“…However, Bcl-2 is overexpressed in the majority of NPC tumors (61-89%), even in the absence of detectable LMP1 expression, and it is postulated that Bcl-2 may play a critical role in promoting cell survival and mediating resistance to chemotherapeutic agents in NPC. [6][7][8][9][10][11][12] Thus, Bcl-2 represents a rational therapeutic target in NPC.…”

Section: Discussionmentioning

confidence: 99%

“…5 Although a direct link between LMP-1 expression, Bcl-2 upregulation and cell survival in NPC is unclear, the majority of NPC tumors overexpress Bcl-2, even in the absence of LMP-1 expression. [6][7][8][9][10][11][12] Given the antiapoptotic function of Bcl-2 and its role in conferring resistance to chemotherapy, it represents a rational target for modulation using antisense strategies in NPC.…”

Section: Epstein-barr Virus (Ebv) Is Causally Linked To Undifferentiamentioning

confidence: 99%

“…Animals were injected with 5 million C666-1 and randomized to CDDP (diamonds), CDDP 1 2 base mismatch control oligo MM (triangles) or CDDP 1 G3139 (squares) (n 5 5-6 per arm). Treatment with oligo was initiated on day 7 at a dose of 25 mg/kg every 3 days 3 5 doses (days [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. CDDP was administered on day 14 (8 mg/kg 3 1).…”

Section: G3139 Inhibits C666-1 Growth and Enhances Sensitivity To Cddmentioning

confidence: 99%

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Systemic Bcl‐2 antisense oligodeoxynucleotide in combination with cisplatin cures EBV⁺ nasopharyngeal carcinoma xenografts in SCID mice

Lacy

Loomis

Grill

et al. 2006

Intl Journal of Cancer

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Nasopharyngeal carcinoma (NPC) is causally linked to Epstein‐Barr virus (EBV), and the EBV oncoprotein, latent membrane protein 1 (LMP‐1), is expressed in the majority of NPCs. LMP‐1 upregulates antiapoptotic genes, including bcl‐2, and Bcl‐2 protein is overexpressed in NPC. Given the antiapoptotic and chemoprotective effects of Bcl‐2, it represents a rational therapeutic target in NPC. We have investigated the antitumor and chemosensitizing effects of the Bcl‐2 antisense oligodeoxynucleotide G3139 (oblimersen, Genasense) in NPC. For these studies, we used the C666‐1 line, a stably infected NPC‐derived line that co‐expresses LMP‐1 and Bcl‐2. We have shown that G3139 treatment of C666‐1 in vitro caused sequence‐dependent suppression of Bcl‐2 protein, inhibition of cell growth and enhanced sensitivity to cisplatin (CDDP), as measured by increased antiproliferative and apoptotic effects. In vivo, G3139 treatment (25 mg/kg every 3 days × 5 doses) delayed engraftment and significantly inhibited growth of established C666‐1 xenografts in SCID mice compared to control oligo‐treated animals. However, G3139 alone did not prevent engraftment or cure established tumors in any animals. In contrast, G3139 treatment (25 mg/kg every 3 days × 5 starting on day 7) in combination with CDDP (8 mg/kg on day 14) completely abrogated tumor engraftment in 80% of animals compared to CDDP (0%) or CDDP + control oligo (0%). When treatment was delayed until tumor was established, G3139 in combination with CDDP significantly inhibited tumor growth compared to CDDP or CDDP + control oligo, and cured 69% animals with established tumors. No animals treated with G3139, CDDP or CDDP + control oligo were cured. Tumor burden and response to treatment correlated with EBV DNA load in serum, measured by real‐time PCR. Western blots of tumor extracts obtained during oligo treatment showed that Bcl‐2 levels were significantly decreased in G3139‐treated animals. Our studies have demonstrated that the Bcl‐2 antisense oligodeoxynucleotide, G3139, has proapoptotic effects in C666‐1, and in combination with CDDP, is curative in C666‐1 NPC xenograft tumors in vivo. The sequence‐dependency of these effects is consistent with an antisense mechanism. These studies suggest that Bcl‐2 may represent a biologically relevant target for the development of novel combinatorial therapies for NPC. © 2006 Wiley‐Liss, Inc.

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Co-expression of p53 and bcl-2 may correlate to the presence of Epstein–Barr virus genome and the expression of proliferating cell nuclear antigen in nasopharyngeal carcinoma

Cited by 32 publications

References 31 publications

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

Lymphoepithelioma-like carcinoma of the urinary tract: a clinicopathological study of 30 pure and mixed cases

Systemic Bcl‐2 antisense oligodeoxynucleotide in combination with cisplatin cures EBV⁺ nasopharyngeal carcinoma xenografts in SCID mice

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Co-expression of p53 and bcl-2 may correlate to the presence of Epstein–Barr virus genome and the expression of proliferating cell nuclear antigen in nasopharyngeal carcinoma

Cited by 32 publications

References 31 publications

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

Lymphoepithelioma-like carcinoma of the urinary tract: a clinicopathological study of 30 pure and mixed cases

Systemic Bcl‐2 antisense oligodeoxynucleotide in combination with cisplatin cures EBV+ nasopharyngeal carcinoma xenografts in SCID mice

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Systemic Bcl‐2 antisense oligodeoxynucleotide in combination with cisplatin cures EBV⁺ nasopharyngeal carcinoma xenografts in SCID mice