Proteomics study on the effect of combined treatment of electrical pulses and tomato lipophilic extract in the downregulation of PCNA in TNBC cell

PARP1 inhibitors (PARPi) are currently approved for BRCAmut metastatic breast cancer, but they have shown limited response in triple negative breast cancer (TNBC) patients. Combination of an Auger emitter with PARPis enables PARP inhibition and DNA strand break induction simultaneously. This will enhance cytotoxicity and additionally allow a theranostic approach. This study presents the radiosynthesis of the Auger emitter [125I] coupled olaparib derivative: [125I]-PARPi-01, and its therapeutic evaluation in a panel of TNBC cell lines. Specificity was tested by a blocking assay. DNA strand break induction was analysed by γH2AX immunofluorescence staining. Cell cycle analysis and apoptosis assays were studied using flow cytometry in TNBC cell lines (BRCAwt/mut). Anchorage independent growth potential was evaluated using soft agar assay. [125I]-PARPi-01 showed PARP1-specificity and higher cytotoxicity than olaparib in TNBC cell lines irrespective of BRCA their status. Cell lines harbouring DNA repair deficiency showed response to [125I]-PARPi-01 monotherapy. Combined treatment with Dox-NP further enhanced therapeutic efficiency in metastatic resistant BRCAwt cell lines. The clonogenic survival was significantly reduced after treatment with [125I]-PARPi-01 in all TNBC lines investigated. Therapeutic efficacy was further enhanced after combined treatment with chemotherapeutics. [125I]-PARPi-01 is a promising radiotherapeutic agent for low radiation dosages, and mono/combined therapies of TNBC.

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Activity of dasatinib with chemotherapy in triple-negative breast cancer cells

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e14605 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e14605-e14605

Author(s):

D. Tryfonopoulos ◽

N. O'Donovan ◽

B. Corkery ◽

M. Clynes ◽

J. Crown

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Kinase Inhibitor ◽

Combined Treatment ◽

Breast Cancer Cell Lines ◽

Breast Cancer Patients ◽

Tnbc Cell ◽

Her 2

e14605 Background: Triple-negative breast cancers (TNBC) lack expression of oestrogen, progesterone, and are HER-2 normal. TNBC cell lines have displayed greater sensitivity to growth inhibition by the multi-target kinase inhibitor, dasatinib, than luminal or HER- 2 positive breast cancer cell lines. The aim of this study was to assess the direct anti-tumor effects of dasatinib in combination with chemotherapy in TNBC. Methods: Four TNBC cell lines (MDA-MB-231, HCC-1143, HCC-1937, MDA-MB-468) were treated with dasatinib in combination with docetaxel, cisplatin or 5'-5' DFUR. IC50 values were calculated for each drug alone by determining response in a 5-day proliferation (acid phosphatase) assay. Combination index (CI) values were determined, using CalcuSyn, to assess the interaction between drugs. Results: Three of the cell lines (MDA-MB-231, HCC- 1143, HCC-1937) were sensitive to dasatinib (IC50 < 1 μM) whereas MDA-MB-468 was resistant (IC50 > 1 μM) (Table). In MDA-MB-231 and HCC-1143 cells, combined treatment with dasatinib and 5'-5'-DFUR displayed synergy (CI<1.0), whereas the combination was additive in HCC-1937 cells (CI=0.98). Combined treatment with dasatinib and cisplatin was synergistic in the three dasatinib sensitive cell lines (CI<1.0). Dasatinib in combination with docetaxel displayed moderate synergy in MDA-MB-231 and HCC-1937 cells (CI<1.0), but was antagonistic in HCC-1143 cells (CI>1.0). Conclusions: Our findings show that the combination of dasatinib with either 5'-5'-DFUR or cisplatin is synergistic in TNBC cell lines, and suggest that combinations of dasatinib with chemotherapy may improve response in triple negative breast cancer patients. [Table: see text] No significant financial relationships to disclose.

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The PAD4 inhibitor GSK484 enhances the radiosensitivity of triple-negative breast cancer

Human & Experimental Toxicology ◽

10.1177/0960327120979028 ◽

2020 ◽

pp. 096032712097902

Author(s):

Lining Wei ◽

Xiangping Wang ◽

Min Luo ◽

Hongzhi Wang ◽

Hao Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Triple Negative Breast Cancer ◽

Protein Level ◽

Triple Negative ◽

Combined Treatment ◽

Arginine Deiminase ◽

Migration And Invasion ◽

Tnbc Cell

Triple-negative breast cancer (TNBC) accounts for approximately 10–20% of all breast cancers and is one of the leading causes of mortality among females. Radiotherapy is essential during the treatment of breast cancer. Growing evidence has indicated that peptidyl arginine deiminase-4 (PAD4) inhibitor can alleviate the development of multiple cancers, including breast cancer, through inhibiting cell proliferation. GSK484 is considered to be a highly potent PAD4-selective inhibitors. However, the potential role and mechanism of GSK484 in TNBC remain unclear. In this study, we intended to explore the effects of GSK484 on the radiosensitivity of TNBC cell lines (MDA-MB-231 and BT-549). We found that the pretreatment of GSK484 enhanced irradiation (IR)-induced inhibitory effects on cell proliferation, migration and invasion. Besides, our findings revealed that GSK484 facilitated TNBC cell apoptosis. IR treatment-induced increase of the protein level of ATG5 and ATG7, and decrease of p62 protein level were countervailed by GSK484. In addition, GSK484 enhanced DNA damage induced by IR. Moreover, in vivo experiments demonstrated that the combined treatment of IR and GSK484 showed an obvious decline of tumor growth in contrast to IR-alone or GSK484-alone treatment. Overall, GSK484 may serve as a radiosensitizer of TNBC through inhibiting IR-induced autophagy.

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Met and HGF inhibition in triple-negative breast cancer cell lines.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1066 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1066-1066 ◽

Cited By ~ 1

Author(s):

Patricia Brid Gaule ◽

Denis Collins ◽

Naomi Walsh ◽

Michael J. Duffy ◽

John Crown ◽

...

Keyword(s):

Breast Cancer ◽

Growth Inhibition ◽

Cell Lines ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Kinase Inhibitor ◽

Day Treatment ◽

Combined Treatment ◽

Breast Cancer Cell Lines ◽

Tnbc Cell

1066 Background: Basal-like breast cancer (BLBC) is associated with high expression of c-Met. c-Met and its ligand HGF may be rational therapeutic targets for BLBC. We evaluated expression of c-Met and response to c-Met/HGF inhibition alone/in combination with other targeted therapies in triple-negative breast cancer (TNBC) cell lines. Methods: Expression and phosphorylation of c-Met was measured by immunoblotting. qRT-PCR was used to measure HGF mRNA. Cell proliferation was measured by acid phosphatase assay after 5 day treatment with a c-Met inhibitor (CpdA), HGF monoclonal antibody, rilotumamab, a panHER inhibitor (neratinib) and a SRC kinase inhibitor, (saracatinib). Invasion through 0.4 μm Matrigel coated membranes was measured for two cell lines. Results: c-Met and p-Met were detected in 7 and 4 of the 7 TNBC cell lines tested, respectively. HGF mRNA was not detectable in any of the TN cell lines. CpdA inhibited growth in 4 TN cell lines with IC50values ranging from 2.1-7.6 μM. Rilotumumab did not inhibit growth, however combined treatment with CpdA and rilotumumab resulted in significantly increased growth inhibition in 3 of 5 cell lines (Table). CpdA in combination with neratinib significantly improved growth inhibition in MDA-MB-468 cells, and in combination with saracatinib significantly improved growth inhibition in 3 of 5 cell lines (Table). CpdA also inhibited invasion of CAL-85-1 cells by 21.4% (± 10.4%) but not HDQ-P1cells. Conclusions: c-Met may represent a viable molecular target in TNBC. Dual targeting of Met and HGF and/or with EGFR or SRC may increase the efficacy of c-Met inhibition in TNBC. [Table: see text]

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Inhibitors of PD-1/PD-L1 and ERK1/2 impede the proliferation of receptor positive and triple-negative breast cancer cell lines

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03694-4 ◽

2021 ◽

Author(s):

Karen Bräutigam ◽

Elodie Kabore-Wolff ◽

Ahmad Fawzi Hussain ◽

Stephan Polack ◽

Achim Rody ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Combined Treatment ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Tnbc Cell

Abstract Purpose Triple-negative breast cancer (TNBC) is characterized by an unfavorable prognosis and missing systemic therapeutic approaches beside chemotherapy. Targeting the immune checkpoint PD-1/PD-L1 showed promising results in breast cancer and especially in TNBC. The extracellular signal-regulated kinase 1/2 (ERK1/2) is an important driver of carcinogenesis. Here, the effect of combined PD-1/PD-L1 and ERK1/2 inhibitor treatment is investigated of cell growth and intracellular impact of breast cancer cell lines. Methods The IC50 values of each inhibitor and the effect of combined treatment were determined in three TNBC cell lines of different subtypes and one non-TNBC cell line. Phospho-specific antibodies were used in western blot analyses to investigate an effect on ERK1/2 activation. Expressions of immune modulatory and cell cycle-associated genes were examined by quantitative reverse transcription PCR. Results Both inhibitors PD-1/PD-L1 and ERK1/2 impeded the proliferation of TNBC to a higher extent than of non-TNBC. By combined treatment, cell lines were inhibited either synergistically or additively. ERK1/2 and S6 phosphorylation were reduced and expressions of c-Fos and FosL were diminished after ERK1/2 inhibitor as single and combined treatment. Between genes involved in immune modulation, IL-8 was upregulated in TNBC cells after combined treatment. Conclusion In conclusion, combination of PD-1/PD-L1 and ERK1/2 inhibitors showed favorable effects for a new therapy strategy, with better results in TNBC cell lines than in non-TNBC cells. The effects have to be validated in models that can reflect the interaction between immune and tumor cells like the situation in the tumor micro-environment.

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Efficacy of botulinum toxin A, serial casting, and combined treatment for spastic equinus: a retrospective analysis

Developmental Medicine & Child Neurology ◽

10.1017/s0012162205211295 ◽

2005 ◽

Vol 47 (09) ◽

pp. 635

Author(s):

Jean-Pierre Lin

Keyword(s):

Botulinum Toxin ◽

Retrospective Analysis ◽

Botulinum Toxin A ◽

Combined Treatment ◽

Toxin A ◽

Serial Casting

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Hybrid treatment of multilevel revascularization in patients with peripheral arterial disease – a multi-centre study in Korea

VASA ◽

10.1024/0301-1526/a000694 ◽

2018 ◽

Vol 47 (3) ◽

pp. 235-241 ◽

Cited By ~ 2

Author(s):

Soon Cheon Lee ◽

Jin Hyun Joh ◽

Jeong-Hwan Chang ◽

Hyung-Kee Kim ◽

Jang Yong Kim ◽

...

Keyword(s):

Endovascular Treatment ◽

Combined Treatment ◽

Ankle Brachial Index ◽

Primary Patency ◽

Limb Ischaemia ◽

University Hospitals ◽

Multi Centre Study ◽

Free Survival ◽

Technical Success Rate ◽

Hybrid Treatment

Abstract. Background: Endovascular treatment is an alternative first-line management for peripheral artery disease (PAD). Hybrid treatment (HT) is defined as a combined treatment for patients with PAD using endovascular and open surgery, simultaneously performed in an operating room. The results of HT are reportedly good for multilevel revascularization (MR) in patients with chronic limb ischaemia, and even in older high-risk patients. The goal of this study was to examine the clinical and haemodynamic outcomes of HT in patients who need MR. Patients and methods: Nine university hospitals in Korea participated in this multicentre study. A total of 134 patients with multilevel PAD underwent HT and MR. Patients were enrolled from July 2014 to June 2015 and were followed for 18 months. Results: The mean age of the patients was 68.8 ± 9.93 years and 88.1 % were men. Patients with Rutherford category 2 to 3 and 4 to 6 comprised 59.0 % and 42.0 % of the group, respectively. The technical success rate was 100 %. The primary patency rates at 12 and 18 months were 77.6 % and 63.9 %, respectively. The primary-assisted patency rates at 12 and 18 months were both 90.0 %. The pre-operative mean ankle brachial index (0.43 ± 0.23) increased to 0.87 ± 0.23 at six months post-operatively (t-test, p < 0.05). The amputation free survival rate was 97.1 %. Conclusions: Although outcomes of multilevel PAD are reportedly poor when endovascular treatment alone is used, we have shown that HT is a feasible alternative modality for patients with multilevel PAD, with satisfactory amputation-free survival and freedom from re-intervention rates.

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A Case of Catatonia in a 14-Year-Old Girl with Schizophrenia Treated with Electroconvulsive Therapy

Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie ◽

10.1024/1422-4917/a000211 ◽

2013 ◽

Vol 41 (1) ◽

pp. 69-74 ◽

Cited By ~ 10

Author(s):

Frank Häßler ◽

Olaf Reis ◽

Steffen Weirich ◽

Jacqueline Höppner ◽

Birgit Pohl ◽

...

Keyword(s):

Case Report ◽

Treatment Response ◽

Electroconvulsive Therapy ◽

Rating Scale ◽

Combined Treatment ◽

Adolescent Patient

This article presents a case of a 14-year-old female twin with schizophrenia who developed severe catatonia following treatment with olanzapine. Under a combined treatment with amantadine, electroconvulsive therapy (ECT), and (currently) ziprasidone alone she improved markedly. Severity and course of catatonia including treatment response were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS). This case report emphasizes the benefit of ECT in the treatment of catatonic symptoms in an adolescent patient with schizophrenic illness.

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