-
1.
Long-term Outcomes of Oral Vinorelbine in Advanced, Progressive Desmoid Fibromatosis and Influence of CTNNB1 Mutational Status.
Mir, O, Honoré, C, Chamseddine, AN, Dômont, J, Dumont, SN, Cavalcanti, A, Faron, M, Rimareix, F, Haddag-Miliani, L, Le Péchoux, C, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020;(23):6277-6283
Abstract
PURPOSE Desmoid-type fibromatosis (DF) are locally aggressive neoplasms, with a need for effective systemic treatment in case of progression to avoid the short- and long-term complications of local treatments. EXPERIMENTAL DESIGN We retrospectively analyzed the outcomes of adult patients with DF treated with oral vinorelbine (90 mg once weekly) at Gustave Roussy Cancer Institute (Villejuif, Paris, France). Only patients with documented progressive disease according to RECIST v1.1 for more than 3 months (±2 weeks) before treatment initiation were included. RESULTS From 2009 to 2019, 90 out of 438 patients with DF were eligible for this analysis. Vinorelbine was given alone in 56 patients (62%), or concomitantly with endocrine therapy in 34 patients, for a median duration of 6.7 months. A partial response was observed in 29% and stable disease in another 57%. With a median follow-up of 52.4 months, the median time to treatment failure (TTF) was not reached. Progression-free rates at 6 and 12 months were 88.7% and 77.5%, respectively. Concomitant endocrine therapy was associated with longer TTF in women [HR, 2.16; 95% confidence interval (CI), 1.06-4.37; P = 0.03). Among 64 patients with documented CTNNB1 mutational status, p.S45F or p.S45P mutations were associated with longer TTF compared with p.T41A or wild-type tumors (HR, 2.78; 95% CI, 1.23-6.27; P = 0.04). Toxicity profile was favorable, without grade 3-4 toxicity, except for one grade 3 neutropenia. CONCLUSIONS Oral vinorelbine is an effective, affordable, and well-tolerated regimen in patients with advanced, progressive DF. Prolonged activity was observed in patients with tumors harboring CTNNB1 p.S45F or p.S45P mutations.
-
2.
Plant natural products with anti-thyroid cancer activity.
Sharifi-Rad, J, Rajabi, S, Martorell, M, López, MD, Toro, MT, Barollo, S, Armanini, D, Fokou, PVT, Zagotto, G, Ribaudo, G, et al
Fitoterapia. 2020;:104640
Abstract
Thyroid cancer is the most frequent endocrine malignancy, with more than 500,000 cases per year worldwide. Differentiated thyroid cancers are the most common forms with best prognosis, while poorly/undifferentiated ones are rare (2% of all thyroid cancer), aggressive, frequently metastasize and have a worse prognosis. For aggressive, metastatic and advanced thyroid cancer novel antitumor molecules are urgently needed and phytochemical products can be a rational and extensive source, since secondary plant metabolites can guarantee the necessary biochemical variability for therapeutic purpose. Among bioactive molecules that present biological activity on thyroid cancer, resveratrol, curcumin, isoflavones, glucosinolates are the most common and used in experimental model. Most of them have been studied both in vitro and in vivo on this cancer, but rarely in clinical trial. This review summarizes phytochemicals, phytotherapeutics and plant derived compounds used in thyroid cancer.
-
3.
New Insights in Gene Expression Alteration as Effect of Paclitaxel Drug Resistance in Triple Negative Breast Cancer Cells.
Jurj, A, Pop, LA, Zanoaga, O, Ciocan-Cârtiţă, CA, Cojocneanu, R, Moldovan, C, Raduly, L, Pop-Bica, C, Trif, M, Irimie, A, et al
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2020;(4):648-664
Abstract
BACKGROUND/AIMS: Triple negative breast cancer (TNBC) is a highly aggressive form of cancer which lacks targeted therapy options. Thus, TNBC patients have poor outcomes and a decreased survival rate than patients with other types of breast cancers. Due to the lack of surface receptors, TNBC needs a comprehensive investigation to provide more information regarding patient's therapy, as well as to understand the way how to counteract drug resistance mechanisms. Nowadays, chemotherapy remains an unsolved issue which rise a lot of questions in oncology field. METHODS In this article, we investigated the implication of paclitaxel in TNBC cell lines after a prolong administration, after 12, respectively 24 passages followed by evaluation of morphological alteration, mutational pattern by next generation sequencing and the altered gene expression pattern by microarray technology and validation by qRT-PCR of the resistance to therapy relevant genes. RESULTS Using functional assays, we showed that paclitaxel exhibits antiproliferative activity on Hs578T/Pax and MDA-MB-231/Pax demonstrating the activation of cell death mechanisms. Confocal microscopy revealed significant modifications which occur in the morphological structure with a disruption of the actin-filaments and also mitotic catastrophe. The presence of these nuclear alterations is due to some modifications at the cellular and molecular levels. Important alterations at the transcriptomic and genomic levels were observed from this a common drug resistance signature (IL-6, CXCL8, VEGFA, EGR1, PTGS2 and TRIB1) for both cell lines at 24 passages was discovered. Also, an important mutation (TP53) linked with drug response was identified. CONCLUSION These results might be used to furnish novel biomarkers in TNBC, as well as to find a strategy to counteract the resistance to therapy in order to increase survival rate and to enhance the prognosis of patients with TNBC.
-
4.
Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression.
Varghese, E, Liskova, A, Kubatka, P, Mathews Samuel, S, Büsselberg, D
Biomolecules. 2020;(2)
Abstract
Several phytochemicals have been identified for their role in modifying miRNA regulating tumor progression. miRNAs modulate the expression of several oncogenes and tumor suppressor genes including the genes that regulate tumor angiogenesis. Hypoxia inducible factor-1 alpha (HIF-1α) signaling is a central axis that activates oncogenic signaling and acts as a metabolic switch in endothelial cell (EC) driven tumor angiogenesis. Tumor angiogenesis driven by metabolic reprogramming of EC is crucial for tumor progression and metastasis in many different cancers, including breast cancers, and has been linked to aberrant miRNA expression profiles. In the current article, we identify different miRNAs that regulate tumor angiogenesis in the context of oncogenic signaling and metabolic reprogramming in ECs and review how selected phytochemicals could modulate miRNA levels to induce an anti-angiogenic action in breast cancer. Studies involving genistein, epigallocatechin gallate (EGCG) and resveratrol demonstrate the regulation of miRNA-21, miRNA-221/222 and miRNA-27, which are prognostic markers in triple negative breast cancers (TNBCs). Modulating the metabolic pathway is a novel strategy for controlling tumor angiogenesis and tumor growth. Cardamonin, curcumin and resveratrol exhibit their anti-angiogenic property by targeting the miRNAs that regulate EC metabolism. Here we suggest that using phytochemicals to target miRNAs, which in turn suppresses tumor angiogenesis, should have the potential to inhibit tumor growth, progression, invasion and metastasis and may be developed into an effective therapeutic strategy for the treatment of many different cancers where tumor angiogenesis plays a significant role in tumor growth and progression.
-
5.
Ampelopsin Induces DR5-Mediated Apoptotic Cell Death in EBV-Infected Cells through the p38 Pathway.
Yun, SM, Kim, YS, Kim, KH, Hur, DY
Nutrition and cancer. 2020;(3):489-494
Abstract
Ampelopsin (AMP) is a well-known flavonoid that exerts a number of biological and pharmacological effects including anticancer effects against several cancer cell lines. In this study, we investigated the anticancer activity of AMP against Epstein-Barr virus (EBV)-positive cells and its mechanism of action. Our results showed that AMP dose-dependently inhibited cell viability and induced apoptotic cell death in EBV-positive cells without cytotoxicity in EBV-negative cells. In particular, AMP induced caspase-8 dependent apoptosis via upregulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor (DR5). Knockdown of DR5 by RNA interference blocked AMP-induced apoptosis. Furthermore, AMP dose-dependently activated p38 mitogen-activated protein kinases (MAPKs) in EBV-positive cells. Additionally, SB203580 (a p38-MAPK inhibitor) effectively inhibited apoptotic cell death. These results demonstrate that treatment with AMP induces the apoptosis of EBV-positive cells through upregulation of TRAIL/DR5 and activation of p38 signaling. Therefore, these results provide experimental information for developing AMP as a new therapeutic drug against EBV-positive cancer.
-
6.
Curcumin and Photobiomodulation in Chronic Viral Hepatitis and Hepatocellular Carcinoma.
Ailioaie, LM, Litscher, G
International journal of molecular sciences. 2020;(19)
Abstract
Immune modulation is a very modern medical field for targeting viral infections. In the race to develop the best immune modulator against viruses, curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. As a bright yellow component of turmeric spice, curcumin has been the subject of thousands of scientific and clinical studies in recent decades to prove its powerful antioxidant properties and anticancer effects. Curcumin has been shown to influence inter- and intracellular signaling pathways, with direct effects on gene expression of the antioxidant proteins and those that regulate the immunity. Experimental studies have shown that curcumin modulates several enzyme systems, reduces nitrosative stress, increases the antioxidant capacity, and decreases the lipid peroxidation, protecting against fatty liver pathogenesis and fibrotic changes. Hepatitis B virus (HBV) affects millions of people worldwide, having sometimes a dramatic evolution to chronic aggressive infection, cirrhosis, and hepatocellular carcinoma. All up-to-date treatments are limited, there is still a gap in the scientific knowledge, and a sterilization cure may not yet be possible with the removal of both covalently closed circular DNA (cccDNA) and the embedded HBV DNA. With a maximum light absorption at 420 nm, the cytotoxicity of curcumin as photosensitizer could be expanded by the intravenous blue laser blood irradiation (IVBLBI) or photobiomodulation in patients with chronic hepatitis B infection, Hepatitis B e-antigen (HBeAg)-positive, noncirrhotic, but nonresponsive to classical therapy. Photobiomodulation increases DNA repair by the biosynthesis of complex molecules with antioxidant properties, the outset of repairing enzyme systems and new phospholipids for regenerating the cell membranes. UltraBioavailable Curcumin and blue laser photobiomodulation could suppress the virus and control better the disease by reducing inflammation/fibrosis and stopping the progression of chronic hepatitis, reversing fibrosis, and diminishing the progression of cirrhosis, and decreasing the incidence of hepatocellular carcinoma. Photodynamic therapy with blue light and curcumin opens new avenues for the effective prevention and cure of chronic liver infections and hepatocellular carcinoma. Blue laser light and UltraBioavailable Curcumin could be a new valuable alternative for medical applications in chronic B viral hepatitis and hepatocarcinoma, saving millions of lives.
-
7.
Use of antioxidant could ameliorate the negative impact of etoposide on human sperm DNA during chemotherapy.
Rabaça, A, Ferreira, C, Bernardino, R, Alves, M, Oliveira, P, Viana, P, Barros, A, Sousa, M, Sá, R
Reproductive biomedicine online. 2020;(6):856-866
Abstract
RESEARCH QUESTION A previous study showed that N-acetylcysteine (NAC), used after in-vitro exposure to the gonadotoxic chemotherapeutic drug etoposide, has the ability to decrease DNA damage in human spermatozoa; however, it showed no benefit when used before exposure. This study aimed to evaluate the impact of the NAC on the preservation of sperm quality during in-vitro exposure to etoposide. DESIGN Twenty semen samples were submitted to four experimental conditions: control, NAC-only incubation, etoposide-only incubation, and concomitant etoposide and NAC incubation. After in-vitro incubation, semen parameters, sperm chromatin condensation, sperm DNA fragmentation, sperm oxidative stress and sperm metabolism were used to evaluate the role of NAC in protecting human spermatozoa from etoposide. RESULTS Etoposide did not affect semen parameters, nor did it cause sperm oxidative damage or alterations in glycolytic profile. However, it induced chromatin decondensation and DNA fragmentation, which were fully prevented by NAC. CONCLUSIONS NAC was able to protect sperm DNA integrity during etoposide treatment in vitro, suggesting that NAC may be useful as an adjuvant agent in preserving male fertility during chemotherapy treatments.
-
8.
Antitumor effect of baicalin from the Scutellaria baicalensis radix extract in B-acute lymphoblastic leukemia with different chromosomal rearrangements.
Orzechowska, BU, Wróbel, G, Turlej, E, Jatczak, B, Sochocka, M, Chaber, R
International immunopharmacology. 2020;:106114
-
-
Free full text
-
Abstract
Acute B-lymphoblastic leukemia (B-ALL) is the most common hematologic malignancy in children. Many cases of B-ALL harbor chromosomal translocations which are often critical determinants of prognosis. Most of them represent altered transcription factors that impact gene transcription or enhance signaling. B-ALLs harboring the mixed-lineage leukemia 1 (MLL1) gene rearrangements represent aggressive, high-risk type of early childhood leukemias that are usually associated with a very poor prognosis. Therefore, there is an urgent need for novel therapeutic agents as well as new treatment strategies. The objective was to examine the vitro inhibitory effects of Scutellaria baicalensis root extract (SBE) in B-ALL cell lines with different chromosomal rearrangements and in leukemic blasts derived from patients' bone marrow (BMCs). In this study we showed that baicalin which is the main component of the SBE possess antitumor activity against all leukemic cell lines especially those with MLL and PBX1 gene rearrangements. Baicalin inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase, and induced cell death through caspase 3/7 activation. Moreover, baicalin treatment inhibited the glycogen synthase kinase-3β (GSK-3β) by suppressing its phosphorylation at Y216, and upregulated the downstream mediator of the cell cycle arrest - cyclin dependent kinase inhibitor p27Kip1. Bone marrow derived blasts from B-ALL patients also exhibited varied sensitivity towards baicalin with 72% patients sensitive to the SBE and baicalin treatment. Taken together, our findings provide new insights into the anti-cancer properties of baicalin by showing its diverse mode of action which might be related to the different genetic background.
-
9.
Natural tyrosine kinase inhibitors acting on the epidermal growth factor receptor: Their relevance for cancer therapy.
Liang, Y, Zhang, T, Zhang, J
Pharmacological research. 2020;:105164
Abstract
Epidermal growth factor receptor (EGFR), also known as ErbB-1/HER-1, plays a key role in the regulation of the cell proliferation, migration, differentiation, and survival. Since the constitutive activation or overexpression of EGFR is nearly found in various cancers, the applications focused on EGFR are the most widely used in the clinical level, including the therapeutic drugs of targeting EGFR, monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs).Over the past decades, the compounds from natural sources have been a productive source of novel drugs, especially in both discovery and development of anti-tumor drugs by targeting the EGFR pathways as the TKIs. This work presents a review of the compounds from natural sources as potential EGFR-TKIs involved in the regulation of cancer. Moreover, high-throughput drug screening of EGFR-TKIs from the natural compounds has also been summarized.
-
10.
A Compressive Review about Taxol®: History and Future Challenges.
Gallego-Jara, J, Lozano-Terol, G, Sola-Martínez, RA, Cánovas-Díaz, M, de Diego Puente, T
Molecules (Basel, Switzerland). 2020;(24)
Abstract
Taxol®, which is also known as paclitaxel, is a chemotherapeutic agent widely used to treat different cancers. Since the discovery of its antitumoral activity, Taxol® has been used to treat over one million patients, making it one of the most widely employed antitumoral drugs. Taxol® was the first microtubule targeting agent described in the literature, with its main mechanism of action consisting of the disruption of microtubule dynamics, thus inducing mitotic arrest and cell death. However, secondary mechanisms for achieving apoptosis have also been demonstrated. Despite its wide use, Taxol® has certain disadvantages. The main challenges facing Taxol® are the need to find an environmentally sustainable production method based on the use of microorganisms, increase its bioavailability without exerting adverse effects on the health of patients and minimize the resistance presented by a high percentage of cells treated with paclitaxel. This review details, in a succinct manner, the main aspects of this important drug, from its discovery to the present day. We highlight the main challenges that must be faced in the coming years, in order to increase the effectiveness of Taxol® as an anticancer agent.