Serum Caspase-3 and Caspase-7 as  Predictive Factors of Response in Locally Advanced and Metastatic Breast Carcinoma

Hammoud, Hayma; Saleh, Jumana; Bachour, Marroan; Salamoon, Maher

doi:10.4236/jct.2014.56067

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…The finding that serum NT-proBNP decreases in some responders to pembrolizumab requires validation with other data sets. Studies have also shown that the activation of CASP-3 is a requirement for apoptosis induction in response to chemotherapeutic drugs such as taxanes and doxorubicin (31). A study evaluated CASP-3 levels in the serum of 60 patients with locally advanced and metastatic breast cancer and found that the 10 complete responders to chemotherapy showed a 1.7-3-fold increase in serum CASP-3, 24 hours after the completion of the first cycle of treatment.…”

Section: Discussionmentioning

confidence: 99%

Serum PD-1 Is Elevated after Pembrolizumab Treatment but Has No Predictive Value

Music

Iafolla

Ren

et al. 2019

Molecular Cancer Therapeutics

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Immune-checkpoint blockade (ICB) uses antibody targeting of specific inhibitory receptors and ligands. The major limitations of ICB, such as high cost, limited success rate, and immune-related adverse events (irAE), highlight the need for predictive biomarkers. We analyzed preimmunotherapy and post-immunotherapy serum samples of 24 patients treated with pembrolizumab for changes in PD-1 and over 1,000 additional protein markers using a multiplex proximity extension assay (PEA) to identify potential predictive biomarkers of response and/or toxicity. Candidates were selected based on the criteria that at least 2 patients within any of 3 patient groups (responders without irAEs, responders with irAEs, or nonresponders with irAEs) had either a !4-fold increase or 4-fold decrease in expression post-immunotherapy. Female and male control samples were used as technical duplicates. A patient group with no response and no irAEs was used to exclude candidates. Following treatment with pembrolizumab, there was a relative increase of PD-1 in the serum of all patients, compared with controls (average 4.4-fold). We identified 7 additional serum proteins that met our candidate selection criteria. These candidate markers did not have any significant association with response or toxicity to pembrolizumab. Overall, we show that serum PD-1 increases post-therapy with pembrolizumab treatment but has no predictive value for response or toxicity in this small set of patients.

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Section: Discussionmentioning

confidence: 99%

Serum PD-1 Is Elevated after Pembrolizumab Treatment but Has No Predictive Value

Music

Iafolla

Ren

et al. 2019

Molecular Cancer Therapeutics

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“…It maintains the integrity of mitochondria by preventing proapoptotic proteins such as Bax or Bak from initiating this pathway (Ebied et al, 2013). In breast cancer, the expression of Bcl-2 has been associated with the presence of markers of differentiation and with a longer survival in node-negative or nodepositive patients (Hammoud et al, 2014). Caspase-3 plays a key role in both the death receptor pathway, initiated by Caspase-8.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that Caspase-3 activation is required for apoptosis induction in response to chemotherapeutic drugs e.g., Taxanes, 5-fluorouracil, and doxorubicin (Bellarosa et al, 2001). However, little work has been made to evaluate levels of Caspases in serum of patients under treatment (Hammoud et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Hammoud et al, (2014), evaluated caspase-3 level in serum of patients with locally advanced and metastatic breast cancer, treated with the combination of Docetaxel and Doxorubicin, where the caspase-3 level was significantly increased in serum after chemotherapy. Elevation of caspase 3 serum level could be attributed to decrease in tumour volume and consequently apoptotic proteins in responders, however, low level of caspases after the first cycle accompanied with lower levels over time revealed a non-responsive disease (Hammound et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

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BRCA1 Gene Mutations and Influence of Chemotherapy on Autophagy and Apoptotic Mechanisms in Egyptian Breast Cancer Patients

Abdel‐Mohsen

Ahmed²,

Elkerm³

2016

Asian Pacific Journal of Cancer Prevention

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Background: It is well established that mutations in the BRCA1 gene are a major risk factor for breast cancer. Induction of cancer cell death and inhibition of survival are the main principles of cancer therapy. In this context, autophagy may have dual roles in cancer, acting on the one hand as a tumor suppressor and on the other as a mechanism of cell survival that can promote the growth of established tumors. Therefore, understanding the role of autophagy in cancer treatment is critical. Moreover, defects in apoptosis, programmed cell death, may lead to increased resistance to chemotherapy. Purpose: The aim of the present study was to detect BRCA1 gene mutations in order to throw more light on their roles as risk factors for breast cancer in Egypt. Secondly the role of autophagy and apoptosis in determining response to a fluorouracil, doxorubicin, cyclophosphamide (FAC) regimen was investigated. Materials and Methods: Forty-five female breast cancer cases and thirty apparently healthy females were enrolled in the present study. Serum levels of autophagic biomarkers, Beclin 1 and LC3 as well as the serum levels of apoptosis biomarkers Bcl-2 and Caspase-3 were measured before and after chemotherapy. Results: BRCA1 mutations were found in 5 (16.7%) and 44 (99.8%) of the controls and cancer patients, the most frequent being 5382insC followed by C61G and 185 delAG. The results revealed that chemotherapy caused elevation in serum concentration levels of the autophagic biomarkers (Beclin 1 and LC3). This elevation was associated with a significant decrease in serum concentration levels of Bcl-2 and significant increase in caspase-3 concentration levels (apoptotic markers). Several factors may be responsible for the development of breast cancers, where they fall into modifiable and non-modifiable factors. Modifiable factors include; socioeconomic status, radiation exposure, modifiable hormonal factors such as hormone replacement therapy and lifestyle factors such as obesity and cigarette smoking. Non-modifiable risk factors include, age, reproductive factors, family history of breast disease and genetic predisposition (Lakshmi et al., 2013). However, genetic factors are thought to contribute to approximately 5% of all breast cancer cases, but to 25% of cases diagnosed before age 30 years. There are several breast cancer susceptibility genes that have been identified. These genes include in the first degree BRCA1 and BRCA2, and other tumor suppressor genes (TSGs) to a lesser extent, such as p53 (Tam 2010). Mutations of genes BRCA1 and BRCA2 involved in breast cancer susceptibility are Mohamed Ahmed Abdel-Mohsen et al

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“…Breast cancer is the leading cancer and the leading cause of cancer death in women worldwide [1] [2]. This condition was diagnosed in women at a frequency of 24.2% and was responsible for nearly 15% of deaths in 2018 [2]. This cancer is also the first diagnosed and the leading cause of cancer deaths in women in developing countries [1].…”

Section: Introductionmentioning

confidence: 99%

Metastatic Breast Cancer Survival in Pointe Noire: Analysis of 30 Cases

Ngatali¹,

Liboko²,

Eouani³

et al. 2019

OJPathology

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Introduction: Breast cancer is the leading cancer and the leading cause of cancer death in women worldwide. About 5% to 10% of breast cancer patients present with metastases. While the 5-year survival of patients with local breast cancer varies around 98.8%, this survival rate drops to around 26.3% for metastatic patients. The objective of this study was to determine the survival of patients with metastatic breast cancer in resource-limited settings. Patients and Methods: This was a cross-sectional descriptive study that took place in the Cancer Department of the General Hospital of Loandjili in Pointe Noire during the period from January 1, 2013 to December 31, 2018, for duration of 6 years. 30 records of patients over 18 years of age and with histological evidence who received at least 3 courses of chemotherapy were collected. The variables studied were: age, level of education, socioeconomic level, menopausal status, history, WHO status, menopausal status, tumor size, histological type, tumor location, the type of treatment and survival. Survival was calculated by Kaplan Meier method. Fisher's exact test was used to search for correlation between variables. Results: The average age was 52.62 ± 10.96 years old. The extremes were 33 years and 75 years old. The most represented level of education was the primary level in 67% of cases. The majority of patients had low socioeconomic status in 50% of cases. The patients were menopausal in 57% of cases. The antecedents of cancer were present in 13% of cases. 50% of patients had a WHO status performance at 2. The tumor size was greater than 2 cm in 77% of cases. The most represented histological type was invasive ductal carcinoma in 93% of cases. The most represented histological grade was Scharff grade III Richardson bloom in 80% of cases.

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Serum Caspase-3 and Caspase-7 as Predictive Factors of Response in Locally Advanced and Metastatic Breast Carcinoma

Cited by 7 publications

References 22 publications

Serum PD-1 Is Elevated after Pembrolizumab Treatment but Has No Predictive Value

Serum PD-1 Is Elevated after Pembrolizumab Treatment but Has No Predictive Value

BRCA1 Gene Mutations and Influence of Chemotherapy on Autophagy and Apoptotic Mechanisms in Egyptian Breast Cancer Patients

Metastatic Breast Cancer Survival in Pointe Noire: Analysis of 30 Cases

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