| Note | |
| | |
| Entity | Lung cancer |
| Cytogenetics | CASP-9 promoter polymorphisms influence the promoter activity and are associated with the risk of developing lung cancer. |
| Oncogenesis | It has been examined the association of four CASP-9 promoter polymorphisms with the risk of lung cancer in a Korean population comprising 432 lung cancer patients and 432 healthy controls. The -1263 GG genotype was associated with a significantly decreased risk of lung cancer compared with -1263 AA or combined -1263 AA + AG. Moreover, individuals with at least one -712T allele had a significantly increased risk of lung cancer compared with those carrying the -712 CC genotype. In brief, the polymorphisms that result in an higher promoter activity seem to be associated with a decreased risk to develop lung cancer. Polymorphisms in CASP-9 promoter can then be useful markers for determining genetic susceptibility to this cancer. However, the association between CASP-9 polymorphisms and risk of lung cancer seem to be influenced by tobacco smoking, no association being present in never-smoker patients. Moreover, as polymorphisms can show ethnic variations, the observations should be extended to diverse ethnic groups. |
| | |
| Disease | Colon cancer |
| Oncogenesis | Caspase-9 was shown to be downregulated in colon cancer samples in comparison with normal mucosa tissues. Immunohistochemical analysis reveals that the expression of caspase-9 is variable in the healthy enterocytes. However, in the enterocytic component of 12 among 26 cancer samples analyzed, a decrease in caspase-9 immunostaining intensity has been observed: a profile similar, but to a smaller extent, to that observed for caspase 7. |
| | |
| | |
| Entity | Head and neck squamous cell carcinoma |
| Oncogenesis | In a certain type of head and neck squamous cell carcinoma cells (HNSCCs), the inhibition of caspase-9 activity and Apaf-1 expression may represent a mechanism of acquired cisplatin resistance. It has been reported that cisplatin induced caspase-9 activation and apoptosis in cisplatin-sensitive HNSCCs in vitro. On the contrary, the cisplatin-resistant HNSCCs analyzed were not able to activate caspase-9 following cisplatin treatment, thus not responding to the therapy. |
| | |
| | |
| Entity | Testicular germ cell cancer |
| Oncogenesis | Similarly to head and neck squamous cell carcinama cells, failure of activation of caspase-9 induces cisplatin resistance in testicular cancer cells in vitro. Testicular germ cell cancer is a tumor highly responsive to cisplatin-based chemotherpy, but in a few cases a phenomenon of chemoresistence can occour leading to an unfavourable prognosis. In in vitro experiments, it has been shown that a cisplatin-resistant human testicular germ cell cancer cell line (1411HP) failed to activate caspase-9 and apoptosis after cisplatin treatment in comparison with two cisplatin-sensitive human testicular germ cell cancer cell line (2102EP and H12.1). In the resistant cell line, however, it was possible induce a caspase-9 independent apoptosis using a 3.3-fold higher cisplatin dose. |
| | |
| | |
| Entity | Nodal diffuse large B-cell lymphoma |
| Oncogenesis | By using biopsy specimens of primary diffuse large B-cell lymphoma (DLBCL) it has been demonstrated that a cellular profile consistent with inhibition of the caspase-9 pathway is associated with poor response to chemotherapy and fatal outcome. On the contrary, a cellular profile consistent with caspase-8 pathway inhibition is associated with an excellent response to chemotherapy. Identifying the functional status of caspase-9 and caspase-8 in patients may have implications for the outcome prediction and for development of alternative therapeutics strategies. |
| | |
| | |
| Entity | Gastric cancer |
| Oncogenesis | Seven cell lines derived from human gastric cancers were used to investigate the involvement of caspases in chemoresistance mechanisms. Among those examined, the cell line most resistant to apoptotic stimuli expressed the highest levels of the caspase-9 isoform beta, thus confirming the role of caspase-9 in promoting apoptosis in treated cancer cells. |
| | |
| Genomic organization of the human caspase-9 gene on Chromosome 1p36. 1-p36.3. |
| Hadano S, Nasir J, Nichol K, Rasper DM, Vaillancourt JP, Sherer SW, Beatty BG, Ikeda JE, Nicholson DW, Hayden MR |
| Mammalian genome : official journal of the International Mammalian Genome Society. 1999 ; 10 (7) : 757-760. |
| PMID 10384055 |
| |
| Identification of an alternative form of caspase-9 in human gastric cancer cell lines: a role of a caspase-9 variant in apoptosis resistance. |
| Izawa M, Mori T, Satoh T, Teramachi K, Sairenji T |
| Apoptosis : an international journal on programmed cell death. 1999 ; 4 (5) : 321-325. |
| PMID 14634335 |
| |
| Caspase-9 regulation: an update. |
| Johnson CR, Jarvis WD |
| Apoptosis : an international journal on programmed cell death. 2004 ; 9 (4) : 423-427. |
| PMID 15192324 |
| |
| Caspase-9. |
| Kuida K |
| The international journal of biochemistry & cell biology. 2000 ; 32 (2) : 121-124. |
| PMID 10687948 |
| |
| Inhibition of caspase-9 activity and Apaf-1 expression in cisplatin-resistant head and neck squamous cell carcinoma cells. |
| Kuwahara D, Tsutsumi K, Oyake D, Ohta T, Nishikawa H, Koizuka I |
| Auris, nasus, larynx. 2003 ; 30 Suppl : S85-S88. |
| PMID 12543167 |
| |
| Failure of activation of caspase-9 induces a higher threshold for apoptosis and cisplatin resistance in testicular cancer. |
| Mueller T, Voigt W, Simon H, Fruehauf A, Bulankin A, Grothey A, Schmoll HJ |
| Cancer research. 2003 ; 63 (2) : 513-521. |
| PMID 12543810 |
| |
| Immunohistochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas. |
| Muris JJ, Cillessen SA, Vos W, van Houdt IS, Kummer JA, van Krieken JH, Jiwa NM, Jansen PM, Kluin-Nelemans HC, Ossenkoppele GJ, Gundy C, Meijer CJ, Oudejans JJ |
| Blood. 2005 ; 105 (7) : 2916-2923. |
| PMID 15576477 |
| |
| Inhibition of caspase 9 and not caspase 8 mediated apoptosis may determine clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas. |
| Oudejans JJ, Muris JJ, Meijer CJ |
| Cell cycle (Georgetown, Tex.). 2005 ; 4 (4) : 526-528. |
| PMID 15876872 |
| |
| Caspase 7 downregulation as an immunohistochemical marker of colonic carcinoma. |
| Palmerini F, Devilard E, Jarry A, Birg F, Xerri L |
| Human pathology. 2001 ; 32 (5) : 461-467. |
| PMID 11381362 |
| |
| Caspase 9 promoter polymorphisms and risk of primary lung cancer. |
| Park JY, Park JM, Jang JS, Choi JE, Kim KM, Cha SI, Kim CH, Kang YM, Lee WK, Kam S, Park RW, Kim IS, Lee JT, Jung TH |
| Human molecular genetics. 2006 ; 15 (12) : 1963-1971. |
| PMID 16687442 |
| |
| Caspases and cancer: mechanisms of inactivation and new treatment modalities. |
| Philchenkov A, Zavelevich M, Kroczak TJ, Los M |
| Experimental oncology. 2004 ; 26 (2) : 82-97. |
| PMID 15273659 |
| |
| Nuclear localization of procaspase-9 and processing by a caspase-3-like activity in mammary epithelial cells. |
| Ritter PM, Marti A, Blanc C, Baltzer A, Krajewski S, Reed JC, Jaggi R |
| European journal of cell biology. 2000 ; 79 (5) : 358-364. |
| PMID 10887967 |
| |
| A caspase-9 variant missing the catalytic site is an endogenous inhibitor of apoptosis. |
| Seol DW, Billiar TR |
| The Journal of biological chemistry. 1999 ; 274 (4) : 2072-2076. |
| PMID 9890966 |
| |
| Antiangiogenic gene therapy: disruption of neovascular networks mediated by inducible caspase-9 delivered with a transcriptionally targeted adenoviral vector. |
| Song W, Sun Q, Dong Z, Spencer DM, Nez G, Nör JE |
| Gene therapy. 2005 ; 12 (4) : 320-329. |
| PMID 15616606 |
| |
| Mutational analysis of proapoptotic caspase-9 gene in common human carcinomas. |
| Soung YH, Lee JW, Kim SY, Park WS, Nam SW, Lee JY, Yoo NJ, Lee SH |
| APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 2006 ; 114 (4) : 292-297. |
| PMID 16689829 |
| |
| Identification of an endogenous dominant-negative short isoform of caspase-9 that can regulate apoptosis. |
| Srinivasula SM, Ahmad M, Guo Y, Zhan Y, Lazebnik Y, Fernandes-Alnemri T, Alnemri ES |
| Cancer research. 1999 ; 59 (5) : 999-1002. |
| PMID 10070954 |
| |
| Mitochondrial release of caspase-2 and -9 during the apoptotic process. |
| Susin SA, Lorenzo HK, Zamzami N, Marzo I, Brenner C, Larochette N, Prévost MC, Alzari PM, Kroemer G |
| The Journal of experimental medicine. 1999 ; 189 (2) : 381-394. |
| PMID 9892620 |
| |
| Cloning of a novel human caspase-9 splice variant containing only the CARD domain. |
| Wang P, Shi T, Ma D |
| Life sciences. 2006 ; 79 (10) : 934-940. |
| PMID 16780893 |
| |
