The Clinical Relevance and Assessment of Apoptotic Cell Death

Sarkiss, Mona; Hsu, Brenda; El‐Naggar, Adel K.; McDonnell, Timothy J.

doi:10.1097/00125480-199607000-00001

Cited by 8 publications

(4 citation statements)

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“…Additionally, TUNEL assay, which detects DNA strand breaks which could occur as an event in the apoptosis showed a dramatic increase in the TUNEL ( +) cells after the co-treatment compared with the control and single drug application. Altogether, these results suggested that the inhibition of cell proliferation, Bcl-2 and caspase-3 by the co-treatment of Bay 11-7082 and TMZ may occur through the NF-κB mediated apoptosis and they might be tightly coupled 80,81 .…”

Section: Discussionmentioning

confidence: 81%

NF-κB inhibitor with Temozolomide results in significant apoptosis in glioblastoma via the NF-κB(p65) and actin cytoskeleton regulatory pathways

Avci

Ebrahimzadeh-Pustchi

Akay

et al. 2020

Sci Rep

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Glioblastoma (GBM) is the most malignant brain tumor characterized by intrinsic or acquired resistance to chemotherapy. GBM tumors show nuclear factor-κB (NF-κB) activity that has been associated with tumor formation, growth, and increased resistance to therapy. We investigated the effect of NF-κB inhibitor BAY 11-7082 with Temozolomide (TMZ) on the signaling pathways in GBM pathogenesis. GBM cells and patient-derived GBM cells cultured in 3D microwells were co-treated with BAY 11-7082 and TMZ or BAY 11-7082 and TMZ alone, and combined experiments of cell proliferation, apoptosis, wound healing assay, as well as reverse-phase protein arrays, western blot and immunofluorescence staining were used to evaluate the effects of drugs on GBM cells. The results revealed that the co-treatment significantly altered cell proliferation by decreasing GBM viability, suppressed NF-κB pathway and enhanced apoptosis. Moreover, it was found that the co-treatment of BAY 11-7082 and TMZ significantly contributed to a decrease in the migration pattern of patientderived GBM cells by modulating actin cytoskeleton pathway. These findings suggest that in addition to TMZ treatment, NF-κB can be used as a potential target to increase the treatment's outcomes. The drug combination strategy, which is significantly improved by NF-κB inhibitor could be used to better understand the underlying mechanism of GBM pathways in vivo and as a potential therapeutic tool for GBM treatment. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in the central nervous system. Current standard of care therapy includes surgery followed by radiotherapy and concomitant and adjuvant chemotherapy with the alkylating agent Temozolomide (TMZ), which provides survival benefits for patients with GBM 1. However, even with the advances in surgical resection combined with TMZ therapy and irradiation, the prognosis for newly diagnosed GBM patients remains poor. In fact, due to its rapid proliferation, increased invasion and migration capacity and chemoresistance to the alkylating agents the median survival is only 14.6 months with the 'Stupp' regimen (radiation with daily TMZ × 4-6 weeks followed by cyclic TMZ) 2 and 5-year survival rate is less than 6%, which is the lowest long-term survival rate of malignant brain tumors 3-5. TMZ methylates DNA at the O 6 positions of guanine and DNA repair enzyme O 6-methylguanine methyltransferase (MGMT) removes alkyl groups from O 6 position of guanine in DNA making cells resistant to TMZ 6. Therefore, new therapies are necessary to prevent cell proliferation and induce apoptosis for GBM patients. Nuclear factor-kappa B (NF-κB) is a regulatory transcription factor of the Rel gene family including p50, c-Rel, RelB, or p65 subunits. It is involved in the control of tumor cell proliferation, migration, immune response and apoptosis 7-10. Studies have shown that NF-κB gene was involved in the regulation pathways of different cancer types such as thyroid cancer, head and neck squamous cell carcinoma and colorectal canc...

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Section: Discussionmentioning

confidence: 81%

NF-κB inhibitor with Temozolomide results in significant apoptosis in glioblastoma via the NF-κB(p65) and actin cytoskeleton regulatory pathways

Avci

Ebrahimzadeh-Pustchi

Akay

et al. 2020

Sci Rep

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“…There is a growing body of evidence that the efficacy of antitumour treatment is a reflection of the intrinsic ability of tumour cells to response to apoptosis. 27,28 Therefore, it is conceivable that tumours displaying high apoptotic rates are more likely to be affected by chemotherapy. Our results seem to confirm this assumption pointing out that a high AI diminishes the risk of relapse.…”

Section: Discussionmentioning

confidence: 99%

Prognostic relevance of apoptotic cell death in non‐Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression

Korkolopoulou

Angelopoulou²,

Kontopidou³

et al. 1998

Histopathology

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“…30 In thymic tumors, p53 mutation occurs early and is associated with advanced tumor stage and biological aggressiveness. 18,19,21,23,[31][32][33] In pulmonary neuroendocrine neoplasms, p53 mutations tend to occur in more aggressive histological subtypes: it is seldom seen in low-grade tumors, such as in typical carcinoid tumor, but is more frequently evident in atypical carcinoid tumor, large-cell neuroendocrine and small-cell carcinomas.…”

Section: Discussionmentioning

confidence: 99%

p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors

et al. 2004

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Thymic neuroendocrine tumors are biologically aggressive neoplasms with extensive local invasion and high mortality. Although various markers of cellular proliferation and apoptosis have correlated with degrees of tumor differentiation in pulmonary neuroendocrine neoplasms, they have not been systematically studied in thymic neuroendocrine tumors. We immunostained 21 cases of thymic neuroendocrine tumors for p53, MIB-1, and the apoptosis-related markers Bcl-2, Bcl-x, and Bax. By histological classification the cases were low-grade (nine cases), intermediate-grade (eight cases), and high-grade (four cases) thymic neuroendocrine tumors. p53 was expressed in five cases: 1/9 low grade, 3/8 intermediate grade, and 2/4 high grade. The mean cellular proliferation (MIB-1) was 7.1% (range 2-12%) in low-grade thymic neuroendocrine tumors, 6.1% (range 2-15%) in intermediate-grade thymic neuroendocrine tumors, and 34.2% (range 2-80%) in high-grade thymic neuroendocrine tumors. Bcl-2 was expressed in 16 cases: 7/9 low grade, 5/8 intermediate grade, and 4/4 high grade. Bcl-x was expressed in 16 cases: 7/9 low grade, 6/8 intermediate grade, and 3/4 high grade. Bax was expressed in 13 cases: 5/9 low grade, 4/8 intermediate grade, and 4/4 high grade. The presence of mutant p53 in the tumor was associated with a statistically significant decreased mean survival (Po0.05). In contrast, either by positive or negative staining or by the score technique (staining intensity Â percentage of cells staining), the presence of Bcl-x was associated with an increased mean survival (Po0.05). Finally, a Bcl-x : Bax ratio Z1 was also associated with an increased mean survival, as compared to a Bcl-x : Bax ratio Z1 (Po0.05). Our study shows that p53 expression and certain apoptosis markers correlate with survival. The expression of these markers may account for differences in biological behavior.

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The Clinical Relevance and Assessment of Apoptotic Cell Death

Cited by 8 publications

References 0 publications

NF-κB inhibitor with Temozolomide results in significant apoptosis in glioblastoma via the NF-κB(p65) and actin cytoskeleton regulatory pathways

NF-κB inhibitor with Temozolomide results in significant apoptosis in glioblastoma via the NF-κB(p65) and actin cytoskeleton regulatory pathways

Prognostic relevance of apoptotic cell death in non‐Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression

p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors

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