ABSTRACT
Photobiomodulation therapy (PBMT) is the use of red or near-infrared light to heal, restore, and stimulate physiological processes that repair damage caused by trauma or a disease. PBMT is widely used in sports injuries, arthritis, neuropathic pain, and back and neck pain. In recent years, PBMT is a safe and effective tool for toxic reactions associated with cancer treatment, such as oral mucositis in patients undergoing chemo-radiotherapy for head and neck cancer or stem cell transplantation, radiation-associated dry mouth, taste disorders, radiation dermatitis, post-radiotherapy fibrosis, and lymphedema associated with head and neck cancer and breast cancer. However, the equipment and optimal dosimetric parameters for PBMT have not been fully defined and need to be further explored.
ABSTRACT
Molecular target anticancer drugs are commonly used in various forms of cancers. It is a concern that the risk of serious adverse events (SAEs) and fatal adverse events (FAEs) of molecular target drugs are increasing. An up-to-date meta-analysis of all Phase II/III/IV randomized trials of molecular target anticancer drugs was conducted to calculate the increased risk of SAEs and FAEs. A systematic search of PubMed, Web of Science, and Cochrane Library up to April 6, 2017, was conducted. The study enrolled Phase II/III/IV randomized trials of cancer that compared molecular target drugs alone versus placebo or performed single-arm analysis of molecular target drugs. Data on SAEs and FAEs were extracted from the included studies and pooled to compute risk ratio (RR), the overall incidence, and 95% confidence interval (CI). In this meta-analysis, a total of 19,965 and 26,642 patients in randomized 53 and 65 Phase II/II/IV trials were included in the analysis of SAEs and FAEs associated with molecular target anticancer drug, respectively. There were significant differences in the relationship of molecular target anticancer drugs with SAEs (RR = 1.57, 95% CI = 1.35–1.82, P < 0.01, I2 = 81%) and FAEs (RR = 1.51, 95% CI = 1.19–1.91, P < 0.01, I2 = 0%) compared to placebo. The overall incidence of SAEs and FAEs was 0.269 (95% CI = 0.262–0.276, P < 0.01) and 0.023 (95% CI = 0.020–0.025, P < 0.01), respectively. Molecular target anticancer drugs significantly increased the risk of SAEs and FAEs. For patients taking molecular target drugs, efforts are needed to prevent the occurrence of SAEs and FAEs
ABSTRACT
G protein coupled receptors (GPCRs) have emerged as the most potential target for a number of drug discovery programs ranging from control of blood pressure, diabetes, cure for genetic diseases to treatment of cancer. A panel of different ligands including hormones, peptides, ions and small molecules is responsible for activation of these receptors. Molecular genetics has identified key GPCRs, whose mutations or altered expressions are linked with tumorgenicity. In this review, we discussed recent advances regarding the involvement of GPCRs in the development of cancers and approaches to manipulating the mechanism behind GPCRs involved tumor growth and metastasis to treat different types of human cancer. This review provides an insight into the current scenario of GPCR-targeted therapy, progress to date and the challenges in the development of anticancer drugs.
ABSTRACT
Globally, peptide-based anticancer therapies have drawn much attention. Marine organisms are a reservoir of anticancer peptides that await discovery. In this study, we aimed to identify cytotoxic oligopeptides from Sarcophyton glaucum. Peptides were purified from among the S. glaucum hydrolysates produced by alcalase, chymotrypsin, papain, and trypsin, guided by a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay on the human cervical cancer (HeLa) cell line for cytotoxicity evaluation. Purification techniques adopted were membrane ultrafiltration, gel filtration chromatography, solid phase extraction (SPE), and reversed-phase high-performance liquid chromatography (RP-HPLC). Purified peptides were identified by de novo peptide sequencing. From papain hydrolysate, three peptide sequences were identified: AGAPGG, AERQ, and RDTQ (428.45, 502.53, and 518.53 Da, respectively). Peptides synthesized from these sequences exhibited cytotoxicity on HeLa cells with median effect concentration (EC50) values of 8.6, 4.9, and 5.6 mmol/L, respectively, up to 5.8-fold stronger than the anticancer drug 5-fluorouracil. When tested at their respective EC50, AGAPGG, AERQ, and RDTQ showed only 16%, 25%, and 11% cytotoxicity to non-cancerous Hek293 cells, respectively. In conclusion, AERQ, AGAPGG, and RDTQ are promising candidates for future development as peptide-based anticancer drugs.
Subject(s)
Animals , Humans , Amino Acid Sequence , Anthozoa/chemistry , Antineoplastic Agents/pharmacology , Chromatography, Gel , Chromatography, High Pressure Liquid , Chromatography, Reverse-Phase , Cytotoxins/pharmacology , Drug Discovery , HEK293 Cells , HeLa Cells , Hydrolysis , Marine Toxins/pharmacology , Oligopeptides/pharmacology , Solid Phase Extraction , Tandem Mass SpectrometryABSTRACT
Objective To investigate the effectiveness of excise training on cancer-related fatigue (CRF) and quality of life (QOL) in patients undergoing anticancer treatment. Methods Eight databases (PubMed, Medline, Cochran Library, EMBASE, and four Chinese database)were searched to identify randomized controlled trials (RCTs) that evaluated the effects of excise training on CRF and QOL. The quality of literature was strictly evaluated and data extracted by 2 researchers. Meta-analysis was performed on randomized controlled trials that met the quality criteria. Results Nine RCTs involving 847 patients were included. Pooled results suggested that aerobic exercise can improve the QOL ( SMD=1.17, P=0.002), alleviate the symptoms of CRF ( SMD=-1.14, P=0.000 2), and also have a certain effect within 3-4 weeks after intervention (P < 0.05); resistance training or anti resistance exercise combined with aerobic exercise can not alleviate the patients′ cancer induced fatigue symptoms ( SMD=-0.06, P=0.85), but it can improve the quality of life ( SMD=0.39, P=0.002). Conclusion Patients with anticancer therapy should undergo aerobic exercise under the guidance of professional personnel to alleviate symptoms of cancer-related fatigue and improve their quality of life.
ABSTRACT
Globally, peptide-based anticancer therapies have drawn much attention. Marine organisms are a reservoir of anticancer peptides that await discovery. In this study, we aimed to identify cytotoxic oligopeptides from Sarcophyton glaucum. Peptides were purified from among the S. glaucum hydrolysates produced by alcalase, chymotrypsin, papain, and trypsin, guided by a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay on the human cervical cancer (HeLa) cell line for cytotoxicity evaluation. Purification techniques adopted were membrane ultrafiltration, gel filtration chromatography, solid phase extraction (SPE), and reversed-phase high-performance liquid chromatography (RP-HPLC). Purified peptides were identified by de novo peptide sequencing. From papain hydrolysate, three peptide sequences were identified: AGAPGG, AERQ, and RDTQ (428.45, 502.53, and 518.53 Da, respectively). Peptides synthesized from these sequences exhibited cytotoxicity on HeLa cells with median effect concentration (EC50) values of 8.6, 4.9, and 5.6 mmol/L, respectively, up to 5.8-fold stronger than the anticancer drug 5-fluorouracil. When tested at their respective EC50, AGAPGG, AERQ, and RDTQ showed only 16%, 25%, and 11% cytotoxicity to non-cancerous Hek293 cells, respectively. In conclusion, AERQ, AGAPGG, and RDTQ are promising candidates for future development as peptide-based anticancer drugs.
ABSTRACT
Objective@#To investigate the effectiveness of excise training on cancer-related fatigue (CRF) and quality of life (QOL) in patients undergoing anticancer treatment.@*Methods@#Eight databases (PubMed, Medline, Cochran Library, EMBASE, and four Chinese database) were searched to identify randomized controlled trials (RCTs) that evaluated the effects of excise training on CRF and QOL. The quality of literature was strictly evaluated and data extracted by 2 researchers. Meta-analysis was performed on randomized controlled trials that met the quality criteria.@*Results@#Nine RCTs involving 847 patients were included. Pooled results suggested that aerobic exercise can improve the QOL (SMD=1.17, P=0.002), alleviate the symptoms of CRF (SMD=-1.14, P=0.000 2), and also have a certain effect within 3-4 weeks after intervention (P < 0.05); resistance training or anti resistance exercise combined with aerobic exercise can not alleviate the patients′ cancer induced fatigue symptoms (SMD=-0.06, P=0.85), but it can improve the quality of life (SMD=0.39, P=0.002).@*Conclusion@#Patients with anticancer therapy should undergo aerobic exercise under the guidance of professional personnel to alleviate symptoms of cancer-related fatigue and improve their quality of life.
ABSTRACT
The methylation of histone lysine plays a pivotal role in epigenetic regulation of gene expression. Histone lysine methylation modifications have 5 sites within histone H3(K4, K9, K27, K36, K79)and 1 site within histone H4(K20). Methylation at various sites has been shown to lead to transcriptional activation or silencing. Histone lysine methyltransferases(HKMTs)and histone lysine demethylases(HKDMs)collectively regulate the methylation modification state of histone lysine. It was reported that the mis-regulation of HKDMs is associated with the occurring and resistance of numerous malignant tumors, so more and more attention are received to HKDMs. Therefore, it is great significant in the study and development of HKDMs inhibitors. The inhibitors could be served not only as a tool in the investigation of the biological function, but also could be used as novel anti-cancer agents in the anticancer therapy. In this review, we provide a short summary of the HKDMs inhibitors recently reported and their potential in the treatment of diseases.
ABSTRACT
A correction of a coauthor's name from Chigusa Nakamura to Chigusa Nakagawa on the author list and the abstract.
ABSTRACT
<b>Purpose</b>: From shortly after the fentanyl patch became commercially available, we have been using it as part of our armamentarium for cancer therapy to produce a reliable analgesic effect from the active treatment period to the terminal stage in patients who are expected to develop resistance to oral analgesics. To confirm the usefulness of fentanyl patch, a retrospective study was conducted to determine its efficacy and safety. <b>Method</b>: A survey was conducted of 28 cancer patients who were undergoing pharmacological pain control. The following parameters were recorded: opioids administered prior to fentanyl patch use, reasons for switching to fentanyl patch, duration of administration and dosage of fentanyl patch, pain score before switching to fentanyl patch, adverse effects (nausea, vomiting, constipation and drowsiness), and the results of clinical tests. <b>Results</b>: The major reasons for switching to fentanyl patch were: "pain control with oral agents was expected to become difficult in future" and "adverse effects of chemotherapy were noted or were likely to develop". The mean duration of fentanyl patch use was 133 days, during which time the pain score and the constipation symptom were significantly reduced. No significant difference was found with nausea, vomiting, drowsiness or the results of clinical tests. <b>Conclusion</b>: It is concluded that fentanyl patch is a highly useful opioid for analgesia when administered during chemotherapy for cancer and continued to the terminal stage.
ABSTRACT
Hypoxia-inducible factor (HIF-1) is an oxygen-dependent transcriptional activator, which plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and one of three subunits (HIF-1alpha, HIF-2alpha or HIF-3alpha). The stability and activity of HIF-1alpha are regulated by various post-translational modifications, hydroxylation, acetylation, and phosphorylation. Therefore, HIF-1alpha interacts with several protein factors including PHD, pVHL, ARD-1, and p300/CBP. Under normoxia, the HIF-1alpha subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)- mediated ubiquitin-proteasome pathway. The association of pVHL and HIF-1alpha under normoxic conditions is triggered by the hydroxylation of prolines and the acetylation of lysine within a polypeptide segment known as the oxygen-dependent degradation (ODD) domain. On the contrary, in the hypoxia condition, HIF-1alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 are especially related to angiogenesis, cell proliferation/survival, and glucose/iron metabolism. Moreover, it was reported that the activation of HIF-1alpha is closely associated with a variety of tumors and oncogenic pathways. Hence, the blocking of HIF-1a itself or HIF-1alpha interacting proteins inhibit tumor growth. Based on these findings, HIF-1 can be a prime target for anticancer therapies. This review summarizes the molecular mechanism of HIF-1a stability, the biological functions of HIF-1 and its potential applications of cancer therapies.
Subject(s)
Humans , Alternative Splicing , Gene Expression Regulation , Genetic Therapy , Growth Substances/metabolism , Protein Isoforms/chemistry , Protein Subunits/genetics , Signal Transduction/physiology , Transcription Factors/chemistry , Transcription, GeneticABSTRACT
Hypoxia plays a major role in the induction of angiogenesis during tumor development. One mechanism by which tumor cells respond to a reduced oxygen level is via the activation of hypoxia-inducible factor-1 (HIF-1). HIF-1 is an oxygen-dependent transcriptional activator that plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and the highly regulated HIF-1 alpha subunits. The stability and activity of HIF-1alpha are regulated by various post-translational modifications, hydroxylation, acetylation, phosphorylation and sumoyaltion. Therefore, HIF-1alpha interacts with several protein factors including PHD, pVHL, ARD-1, SUMO and p300/ CBP. Under normoxia, the HIF-1alpha subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)-mediated ubiquitin/proteasome pathway. The association of pVHL and HIF-1alpha under normoxic conditions is triggered by the hydroxylation of prolines and the acetylation of lysine within a polypeptide segment known as the oxygen-dependent degradation (ODD) domain. On the contrary, under the hypoxia condition, the HIF-1alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Under hypoxic conditions, HIF-1 eventually acts as a master regulator of numerous hypoxia-inducible genes. The target genes of HIF-1 are especially related to angiogenesis, cell proliferation and survival, and to glucose and iron metabolism. Moreover, it was reported that the activation of HIF-1alpha is closely associated with a variety of tumors and oncogenic pathways. Hence, the blocking of HIF-1alpha itself or the blocking of HIF-1alpha interacting proteins inhibits tumor growth. Based on these findings, HIF-1 can be a prime target for anticancer therapies. Therefore, this review summarizes the molecular mechanism of HIF-1alpha stability, the biological functions of HIF-1 and its potential applications for cancer therapies.