-
1.
Quality of life in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer.
Taira, N, Kashiwabara, K, Tsurutani, J, Kitada, M, Takahashi, M, Kato, H, Kikawa, Y, Sakata, E, Naito, Y, Hasegawa, Y, et al
Breast cancer (Tokyo, Japan). 2022;(1):131-143
-
-
Free full text
-
Abstract
BACKGROUND To report our findings on quality of life (QoL) in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). METHODS Patients with HER2-negative MBC were randomly assigned to three different doses of q3w nab-PTX (SD 260 mg/m2 vs. MD: 220 mg/m2 vs. LD 180 mg/m2). QoL was assessed at baseline and during the second, fourth and sixth courses of treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Cancer Fatigue Scale (CFS) and EuroQol 5-Dimension (EQ-5D). Comparisons were performed with mixed-model repeated measures (MMRM). RESULTS A total of 141 patients were enrolled in the parent study, and 136 (96%) (44, 45 and 47 in the SD, MD, and LD groups) were included in the analysis. MMRM analysis showed that the difference from the baseline FACT-Taxane trial outcome index at MD and LD were significantly higher than that at SD (MD vs. SD P < 0.001, LD vs. SD P < 0.001). Differences from baseline for FACT-Taxane total, physical and emotional well-being, and taxane subscale scores at MD and LD were also higher than at SD. The difference from baseline for the CFS score at LD was lower than at SD (P = 0.013) and those for EQ-5D utility scores at MD and LD were higher than at SD (MD vs. SD P = 0.011, LD vs. SD P < 0.001). CONCLUSION QoL of patients treated with 220 or 180 mg/m2 of q3w nab-PTX was significantly better than that of patients treated with 260 mg/m2. TRIAL REGISTRATION The protocol was registered at the website of the University Hospital Medical Information Network (UMIN), Japan (protocol ID: UMIN000015516), on 01/11/2014. Details are available at the following address: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017916.
-
2.
Research on the mechanisms of taraxerol for the treatment of gastric cancer effect based on network pharmacology.
Huo, B, Song, Y, Tan, B, Li, J, Zhang, J, Zhang, F, Chang, L
International journal of immunopathology and pharmacology. 2022;:20587384211063962
Abstract
BACKGROUND Modern pharmacological studies have shown that traditional Chinese medicine (TCM) Taraxacum mongolicum possesses anti-cancer activity. Taraxerol (TRX) is a pentacyclic triterpene isolated from T. mongolicum, which is widely used in clinical treatment, and its anti-cancer effects have been extensively studied. However, the effects and molecular mechanism of TRX in gastric cancer (GC) have not been fully explicated. METHODS We used public databases to derive information on potential targets of TRX and proteins related to GC. Also, STRING and R3.6.2 software were used to analyze the protein-protein interaction (PPI). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were done to explain the potential mechanism underlying the regulatory role of TRX in GC. The role of TRX in GC was verified by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, apoptosis analysis, Transwell assay, and wound healing assay, and the key signaling pathways were verified. RESULTS We identified 135 potential targets for the treatment of GC via network pharmacological analysis. GO and KEGG enrichment analysis showed that steroid hormone receptor activity and the PI3K/AKT signaling pathway were the biological processes and pathways with the highest degree of enrichment. Additionally, cellular experiments revealed that TRX inhibited the proliferation, migration, and invasion of GC cells as well as induced G1 phase arrest and apoptosis in GC cells. CONCLUSION Here, we used multi-target and multi-pathway network pharmacological analysis to verify the anti-cancer activity of TRX in GC. Also, in vitro experimental data were used to derive the potential molecular mechanism.
-
3.
Pediatric Oncology Patients With Vincristine-Induced Recurrent Laryngeal Nerve Palsy: Two Case Reports and a Brief Review of Literature.
Tay, SY, Foster, J, Heczey, A, Sitton, M
Ear, nose, & throat journal. 2021;(10):NP459-NP463
-
-
Free full text
-
Abstract
INTRODUCTION Vincristine (VCR) is a chemotherapeutic agent used widely in the treatment of hematologic and solid tumors, known to result in neurotoxicity, especially with cumulative administrations. Bilateral vocal fold palsy (VFP) is a rare but life-threatening complication of VCR. We report 2 patients with hepatoblastoma presenting with stridor following VCR treatment and propose a management plan. METHODS Electronic medical records of oncology patients treated at a tertiary hospital with VCR-induced VFP were reviewed. Literature review was performed in PubMed using the terms: hoarseness, VFP, stridor, vincristine. RESULTS A total of 23 children with VCR-induced VFP were identified from the literature review and adding on our 2 cases. Seventeen (77.3%) were male and 5 (22.7%) were female. The median presenting age was 36.0 months (5-204 months). Acute lymphoblastic leukemia, 15 of 23 (65.2%), was the most common malignancy. Eighteen patients (78.3%) had bilateral VFP and 5 (21.7%) had unilateral VFP. The mean time to VF function recovery was 167.3 days (median: 200.5 days, range: 7-270 days) in the intervention group versus 72.1 days (median: 31.5 days, range: 3-240 days) in the conservative group. One patient in the intervention group had persistent VFP. Sixteen patients (69.6%) were observed, 4 (17.4%) underwent tracheostomy, 1 (4.35%) was intubated, 1 (4.35%) underwent cordectomy, and 1 (4.35%) required positive pressure support. Vincristine was restarted in 12 patients (54.5%), of which 4 developed recurrence of airway symptoms and had to stop VCR. CONCLUSION A new-onset hoarseness or stridor in a child on VCR should raise the suspicions of VFP. The assumption of an upper respiratory-induced hoarseness or stridor should be avoided. Decisions regarding readministration of VCR and possible airway interventions should be made via a multidisciplinary team approach.
-
4.
Mechanism of Tetrandrine Against Endometrial Cancer Based on Network Pharmacology.
Shang, W, Zhang, J, Song, H, Zhu, S, Zhang, A, Hua, Y, Han, S, Fu, Y
Drug design, development and therapy. 2021;:2907-2919
Abstract
BACKGROUND Endometrial cancer (EC) is one of the most common gynaecological malignancies, and its incidence has been rising over the past decade. Tetrandrine, a bisbenzylisoquinoline alkaloid, has been isolated from a vine used in traditional Chinese medicine, Stephania tetrandra. However, the key mechanism of tetrandrine in EC is still unclear. PURPOSE This research was designed to predict the molecular mechanisms of tetrandrine against EC based on network pharmacology and to further verify these predictions by in vitro experiments. METHODS The potential therapeutic targets of tetrandrine against EC were predicted by using public databases. Afterwards, the protein-protein interaction (PPI) network of the common targets was constructed, and the key gene targets were obtained. Biological function and pathway enrichment analyses were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Furthermore, molecular docking and in vitro experiments were carried out to verify the predictions. The cell counting kit‑8 (CCK‑8) assay, Hoechst 33258 staining, flow cytometry analysis, qRT-PCR, Western blot analysis and an immunofluorescence assay were performed. RESULTS Our findings identified 111 potential therapeutic targets of tetrandrine against EC. We obtained 7 key gene targets from the PPI network analysis. Furthermore, GO enrichment analysis indicated that these targets were mainly associated with metabolic processes, responses to stimulus, and biological regulation. The KEGG pathway analysis showed that the common targets were mainly distributed in the PI3K/Akt signalling pathway. A potential interaction of tetrandrine with Akt1 was revealed by molecular docking. In addition, in vitro experiments showed that tetrandrine significantly inhibited cell proliferation and induced apoptosis in Ishikawa and HEC-1-B cells in dose- and time-dependent manners. The results also revealed that tetrandrine can downregulate the expression of Bcl-2 and upregulate the expression of Bax at the mRNA level. The mRNA levels of Akt were not significantly different in the various tetrandrine (0, 10 and 20µM) groups. However, Western blot analysis demonstrated that the protein expression ratios of p-Akt/Akt decreased at the protein level. The results were further confirmed by immunofluorescence assays. CONCLUSION Based on bioinformatic analysis and experimental verification, our findings demonstrated that tetrandrine exerted tumour-suppressive effects on EC by regulating the PI3K/Akt signalling pathway.
-
5.
Antiproliferative and palliative activity of flavonoids in colorectal cancer.
Fernández, J, Silván, B, Entrialgo-Cadierno, R, Villar, CJ, Capasso, R, Uranga, JA, Lombó, F, Abalo, R
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;:112241
Abstract
Flavonoids are plant bioactive compounds of great interest in nutrition and pharmacology, due to their remarkable properties as antioxidant, anti-inflammatory, antibacterial, antifungal and antitumor drugs. More than 5000 different flavonoids exist in nature, with a huge structural diversity and a plethora of interesting pharmacological properties. In this work, five flavonoids were tested for their potential use as antitumor drugs against three CRC cell lines (HCT116, HT-29 and T84). These cell lines represent three different stages of this tumor, one of which is metastatic. Xanthohumol showed the best antitumor activity on the three cancer cell lines, even better than that of the clinical drug 5-fluorouracil (5-FU), although no synergistic effect was observed in the combination therapy with this drug. On the other hand, apigenin and luteolin displayed slightly lower antitumor activities on these cancer cell lines but showed a synergistic effect in combination with 5-FU in the case of HTC116, which is of potential clinical interest. Furthermore, a literature review highlighted that these flavonoids show very interesting palliative effects on clinical symptoms such as diarrhea, mucositis, neuropathic pain and others often associated with the chemotherapy treatment of CRC. Flavonoids could provide a double effect for the combination treatment, potentiating the antitumor effect of 5-FU, and simultaneously, preventing important side effects of 5-FU chemotherapy.
-
6.
Bioprospecting of Natural Compounds from Brazilian Cerrado Biome Plants in Human Cervical Cancer Cell Lines.
Rosa, MN, E Silva, LRV, Longato, GB, Evangelista, AF, Gomes, INF, Alves, ALV, de Oliveira, BG, Pinto, FE, Romão, W, de Rezende, AR, et al
International journal of molecular sciences. 2021;(7)
Abstract
Cervical cancer is the third most common in Brazilian women. The chemotherapy used for the treatment of this disease can cause many side effects; then, to overcome this problem, new treatment options are necessary. Natural compounds represent one of the most promising sources for the development of new drugs. In this study, 13 different species of 6 families from the Brazilian Cerrado vegetation biome were screened against human cervical cancer cell lines (CCC). Some of these species were also evaluated in one normal keratinocyte cell line (HaCaT). The effect of crude extracts on cell viability was evaluated by a colorimetric method (MTS assay). Extracts from Annona crassiflora, Miconia albicans, Miconia chamissois, Stryphnodendron adstringens, Tapirira guianensis, Xylopia aromatica, and Achyrocline alata showed half-maximal inhibitory concentration (IC50) values < 30 μg/mL for at least one CCC. A. crassiflora and S. adstringens extracts were selective for CCC. Mass spectrometry (Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (ESI FT-ICR MS)) of A. crassiflora identified fatty acids and flavonols as secondary compounds. One of the A. crassiflora fractions, 7C24 (from chloroform partition), increased H2AX phosphorylation (suggesting DNA damage), PARP cleavage, and cell cycle arrest in CCC. Kaempferol-3-O-rhamnoside and oleic acid were bioactive molecules identified in 7C24 fraction. These findings emphasize the importance of investigating bioactive molecules from natural sources for developing new anti-cancer drugs.
-
7.
Vocal cord paralysis secondary to vincristine treatment in children: A case series of seven children and literature review.
Godbehere, J, Payne, J, Thevasagayam, R
Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2021;(5):1114-1118
-
8.
Bergamottin and 5-Geranyloxy-7-methoxycoumarin Cooperate in the Cytotoxic Effect of Citrus bergamia (Bergamot) Essential Oil in Human Neuroblastoma SH-SY5Y Cell Line.
Maugeri, A, Lombardo, GE, Musumeci, L, Russo, C, Gangemi, S, Calapai, G, Cirmi, S, Navarra, M
Toxins. 2021;(4)
Abstract
The plant kingdom has always been a treasure trove for valuable bioactive compounds, and Citrus fruits stand out among the others. Bergamottin (BRG) and 5-geranyloxy-7-methoxycoumarin (5-G-7-MOC) are two coumarins found in different Citrus species with well-acknowledged pharmacological properties. Previously, they have been claimed to be relevant in the anti-proliferative effects exerted by bergamot essential oil (BEO) in the SH-SY5Y human neuroblastoma cells. This study was designed to verify this assumption and to assess the mechanisms underlying the anti-proliferative effect of both compounds. Our results demonstrate that BRG and 5-G-7-MOC are able to reduce the proliferation of SH-SY5Y cells, inducing apoptosis and increasing cell population in sub-G0/G1 phase. Moreover, we demonstrated the pro-oxidant activity of the two coumarins that increased reactive oxygen species and impaired mitochondrial membrane potential. From a molecular point of view, BRG and 5-G-7-MOC were able to modulate apoptosis related factors at both protein and gene levels. Lastly, we evaluated the synergistic effect of their combination, finding that the highest synergy was observed at a concentration ratio similar to that occurring in the BEO, supporting our initial hypothesis. Taken together, our results deepen the knowledge regarding the effect of BRG and 5-G-7-MOC in SH-SY5Y cells, emphasizing the relevance of their cooperation in achieving this effect.
-
9.
Perspectives and controversies regarding the use of natural products for the treatment of lung cancer.
Wen, T, Song, L, Hua, S
Cancer medicine. 2021;(7):2396-2422
Abstract
Lung cancer is the leading cause of cancer-related mortality both in men and women and accounts for 18.4% of all cancer-related deaths. Although advanced therapy methods have been developed, the prognosis of lung cancer patients remains extremely poor. Over the past few decades, clinicians and researchers have found that chemical compounds extracted from natural products may be useful for treating lung cancer. Drug formulations derived from natural compounds, such as paclitaxel, doxorubicin, and camptothecin, have been successfully used as chemotherapeutics for lung cancer. In recent years, hundreds of new natural compounds that can be used to treat lung cancer have been found through basic and sub-clinical research. However, there has not been a corresponding increase in the number of drugs that have been used in a clinical setting. The probable reasons may include low solubility, limited absorption, unfavorable metabolism, and severe side effects. In this review, we present a summary of the natural compounds that have been proven to be effective for the treatment of lung cancer, as well as an understanding of the mechanisms underlying their pharmacological effects. We have also highlighted current controversies and have attempted to provide solutions for the clinical translation of these compounds.
-
10.
A network pharmacology-based investigation on the bioactive ingredients and molecular mechanisms of Gelsemium elegans Benth against colorectal cancer.
Que, W, Chen, M, Yang, L, Zhang, B, Zhao, Z, Liu, M, Cheng, Y, Qiu, H
BMC complementary medicine and therapies. 2021;(1):99
Abstract
BACKGROUND Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Gelsemium elegans Benth (GEB) is a traditional Chinese medicine commonly used for treatment for gastrointestinal cancer, including CRC. However, the underlying active ingredients and mechanism remain unknown. This study aims to explore the active components and the functional mechanisms of GEB in treating CRC by network pharmacology-based approaches. METHODS Candidate compounds of GEB were collected from the Traditional Chinese Medicine@Taiwan, Traditional Chinese Medicines Integrated Database, Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine, and published literature. Potentially active targets of compounds in GEB were retrieved from SwissTargetPrediction databases. Keywords "colorectal cancer", "rectal cancer" and "colon cancer" were used as keywords to search for related targets of CRC from the GeneCards database, then the overlapped targets of compounds and CRC were further intersected with CRC related genes from the TCGA database. The Cytoscape was applied to construct a graph of visualized compound-target and pathway networks. Protein-protein interaction networks were constructed by using STRING database. The DAVID tool was applied to carry out Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis of final targets. Molecular docking was employed to validate the interaction between compounds and targets. AutoDockTools was used to construct docking grid box for each target. Docking and molecular dynamics simulation were performed by Autodock Vina and Gromacs software, respectively. RESULTS Fifty-three bioactive compounds were successfully identified, corresponding to 136 targets that were screened out for the treatment of CRC. Functional enrichment analysis suggested that GEB exerted its pharmacological effects against CRC via modulating multiple pathways, such as pathways in cancer, cell cycle, and colorectal cancer. Molecular docking analysis showed that the representative compounds had good affinity with the key targets. Molecular dynamics simulation indicated that the best hit molecules formed a stable protein-ligand complex. CONCLUSION This network pharmacology study revealed the multiple ingredients, targets, and pathways synergistically involved in the anti-CRC effect of GEB, which will enhance our understanding of the potential molecular mechanism of GEB in treatment for CRC and lay a foundation for further experimental research.