Apoptosis – associated genes and their role in predicting responses to neoadjuvant breast cancer treatment

Tvrdík, Daniel; Skálová, Helena; Dundr, Pavel; Povýšil, C; Velenská, Z; Berkova, Adela; Staněk, Libor; Petruželka, Luboš

doi:10.12659/msm.882205

Cited by 10 publications

(5 citation statements)

References 32 publications

(36 reference statements)

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“…In this study, two growth promoting genes ( AKT1 and IGF1R ) were down-regulated post-PDT treatment of Caco-2 cells. In breast cancer, the up-regulation of IGF1R and the activation of its downstream signaling molecules have been linked to an inhibition of apoptosis, disease progression, increased resistance to cytotoxic chemo-therapeutic drugs or radiotherapy, and to poor prognosis [58]. Therefore, it is remarkable that IGF1R and AKT1 were down-regulated 24 h post-PDT, as this translates into there being less chance of survival and warrants PDT-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells

Abrahamse

Houreld

2019

IJMS

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Photodynamic therapy (PDT) is a cancer treatment modality that utilizes three components: light (λ 650–750 nm), a photosensitizer (PS) and molecular oxygen, which upon activation renders the modality effective. Colorectal cancer has one of the highest incident rates as well as a high mortality rate worldwide. In this study, a zinc (Zn) metal-based phthalocyanine (ZnPcSmix) PS was used to determine its efficacy for the treatment of colon adenocarcinoma cells (DLD-1 and Caco-2). Photoactivation of the PS was achieved by laser irradiation at a wavelength of 680 nm. Dose responses were performed to establish optimal PS concentration and irradiation fluence. A working combination of 20 µM ZnPcSmix and 5 J/cm2 was used. Biochemical responses were determined after 1 or 24 h incubation post-treatment. Since ZnPcSmix is localized in lysosomes and mitochondria, mitochondrial destabilization analysis was performed monitoring mitochondrial membrane potential (MMP). Cytosolic acidification was determined measuring hydrogen peroxide (H2O2) levels in the cytoplasm. Having established apoptotic cell death induction, an apoptosis PCR array was performed to establish the apoptotic mechanism. In DLD-1 cells, expression of genes included 3 up-regulated and 20 down-regulated genes while in Caco-2 cells, there were 16 up-regulated and 22 down-regulated genes. In both cell lines, in up-regulated genes, there was a combination of pro- and anti-apoptotic genes that were significantly expressed. Gene expression results showed that more tumorigenic cells (DLD-1) went through apoptosis; however, they exhibit increased risk of resistance and recurrence, while less tumorigenic Caco-2 cells responded better to PDT, thus being suggestive of a better prognosis post-PDT treatment. In addition, the possible apoptotic mechanisms of cell death were deduced based on the genetic expression profiling of regulatory apoptotic inducing factors.

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Section: Discussionmentioning

confidence: 99%

Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells

Abrahamse

Houreld

2019

IJMS

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“…However, contradictory clinical associations of FADD expression were also reported. Colorectal cancer cell growth was inhibited by FADD expression [ 29 ] and high FADD expression after neoadjuvant breast cancer treatment was associated with a good prognosis group in breast cancer [ 30 ]. This may be due to the difference in cancer type or primary site from which the tumor has arisen.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive ductal carcinoma of the breast

et al. 2014

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Background11q13 region is a frequently amplified locus in human malignancies. Among the genes located in this region, FADD is one of the alleged driving genes. Because amplification is not generally confined to a single gene and amplified genes may not show increased expression, we need to evaluate clinical significance of changes occurring in 11q13 region to understand their roles in carcinogenesis. Therefore, we screened expressions of FADD and closely located genes (PPFIA1 and TMEM16A) and evaluated the expressions to find clinical significance in invasive ductal carcinoma of the breast.MethodsNinety-eight cases of invasive ductal carcinoma of the breast were collected. Using archival tissues resected from the cases, we built a tissue microarray and used it in immunohistochemistry. We evaluated the association of FADD, PPFIA1, and TMEM16A expression scores with clinicopathological parameters, including disease-free survival.ResultsFADD expression was associated with T stage (P = 0.046). The combined score of FADD, PPFIA1, and TMEM16A gene expressions was associated with perineural invasion (P = 0.022). Although individual gene expressions of TMEM16A, FADD, and PPFIA1 failed to show significant association with disease-free survival, combined gene expression scores did show association with disease-free survival (P = 0.034).ConclusionsFADD, TMEM16A, and PPFIA1 gene expressions as a whole were associated with disease-free survival in breast cancer.

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“…Of interest, Liu et al demonstrated that a high CD70 expression was correlated with worse lung metastasis-free survival, but not with other metastatic sites following relapse of EBC. In addition, gene expression studies showed that CD70 was overexpressed in basal-like compared to Luminal A cancers and that overexpression after NACT was associated with a better outcome [51,181].…”

Section: Markers Predominantly Expressed On T-lymphocytesmentioning

confidence: 99%

Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

Chrétien

Zerdes

Bergh

et al. 2019

Cancers

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Cancer immunotherapy has altered the management of human malignancies, improving outcomes in an expanding list of diseases. Breast cancer - presumably due to its perceived low immunogenicity - is a late addition to this list. Furthermore, most of the focus has been on the triple negative subtype because of its higher tumor mutational load and lymphocyte-enriched stroma, although emerging data show promise on the other breast cancer subtypes as well. To this point the clinical use of immunotherapy is limited to the inhibition of two immune checkpoints, Programmed Cell Death Protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4). Consistent with the complexity of the regulation of the tumor – host interactions and their lack of reliance on a single regulatory pathway, combinatory approaches have shown improved efficacy albeit at the cost of increased toxicity. Beyond those two checkpoints though, a large number of co-stimulatory or co-inhibitory molecules play major roles on tumor evasion from immunosurveillance. These molecules likely represent future targets of immunotherapy provided that the promise shown in early data is translated into improved patient survival in randomized trials. The biological role, prognostic and predictive implications regarding breast cancer and early clinical efforts on exploiting these immune-related therapeutic targets are herein reviewed.

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Apoptosis – associated genes and their role in predicting responses to neoadjuvant breast cancer treatment

Cited by 10 publications

References 32 publications

Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells

Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells

Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive ductal carcinoma of the breast

Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy

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