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ACS Chemical Biology Nov 2021, a genus of blue-green cyanobacteria, is known for its great biological activity due to the presence of a large number of substances that are potentially active against...
, a genus of blue-green cyanobacteria, is known for its great biological activity due to the presence of a large number of substances that are potentially active against tumor cells. This review aimed to evaluate the potential of spp. for the treatment or reduction of several types of cancer, in addition to elucidating the mechanism of action by which their compounds act on tumor cells. A systematic review was carried out in PubMed, Science Direct, LILACS, and SciELO databases, including original studies from 2009 to 2020. A total of 1306 articles were independently assessed according to the eligibility criteria, of which 20 articles were selected and assessed for the risk of bias using seven criteria developed by the authors. spp. of cyanobacteria have been evaluated against eight different types of cancer, mainly colon cancer. Among all the compounds, phycocyanin was the most used, followed by peptides and photosensitizers. In general, compounds from spp. act as anticancer agents by inhibiting the proliferation of tumor cells, triggering cell cycle arrest, and inducing apoptosis via different signaling pathways. In addition, these compounds also exhibited antioxidant, antiangiogenic, and antimetastatic activities. Phycocyanin demonstrated better efficacy against several types of cancer via different activities and therapeutic targets. Furthermore, it was the only molecule that functioned in synergy with other drugs that are already well established for the treatment of cancer.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Humans; Neoplasms; Phycocyanin; Spirulina
PubMed: 34597512
DOI: 10.1021/acschembio.1c00568 -
Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins.Theranostics 2021Classic small molecule inhibitors that directly target pathogenic proteins typically rely on the accessible binding sites to achieve prolonged occupancy and influence... (Review)
Review
Classic small molecule inhibitors that directly target pathogenic proteins typically rely on the accessible binding sites to achieve prolonged occupancy and influence protein functions. The emerging targeted protein degradation (TPD) strategies exemplified by PROteolysis TArgeting Chimeras (PROTACs) are revolutionizing conventional drug discovery modality to target proteins of interest (POIs) that were categorized as "undruggable" before, however, these strategies are limited within intracellular POIs. The novel new degrader technologies such as LYsosome-TArgeting Chimaeras (LYTACs) and Antibody-based PROTACs (AbTACs) have been successfully developed to expand the scope of TPD to extracellular and membrane proteins, fulfilling huge unmet medical needs. Here, we systematically review the currently viable protein degradation strategies, emphasize that LYTACs and AbTACs turn a new avenue for the development of TPD, and highlight the potential challenges and directions in this vibrant field.
Topics: Animals; Cellular Microenvironment; Drug Delivery Systems; Drug Discovery; Humans; Lysosomes; Membrane Proteins; Proteasome Endopeptidase Complex; Proteins; Proteolysis
PubMed: 34373745
DOI: 10.7150/thno.62686 -
Asian Pacific Journal of Cancer... Jun 2021In this study, we aimed to detect Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) frequency in paragangliomas and pheochromocytomas (PPGL) with...
Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) Immunohistochemistry in Pheochromocytoma, Head and Neck Paraganglioma, Thoraco-Abdomino-Pelvic Paragangliomas: Is It a Good Idea to Use in Routine Work?
BACKGROUND
In this study, we aimed to detect Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB) frequency in paragangliomas and pheochromocytomas (PPGL) with immunohistochemistry; compare with Pheochromacytoma of the Adrenal Gland Scaled Score (PASS) classification and analyse the differences between pheochromocytoma (Pheo), head-neck paragangliomas (HNPGL) and thoraco-abdominal-pelvic paraganglioma (TAPPGL) sub-groups.
METHODS
A total 114 PPGL cases (73 HNPGL, 15 TAPPGL and 27 Pheo belonging to 112 cases) are included. Immunohistochemically, SDHB and Ki-67 are investigated and malignancy risks are determined by PASS classification. Results are assessed statistically with chi-square test and p <0,01 is considered significant.
RESULTS
SDHB mutations are observed in 20 of 114 (17.54 %) PPGL cases, 3 (11,12%) of which is Pheo, 12 (16,44) is HNPGL, and 5 (35,71%) is TAPPGL (P <0,02). While 15/82 (18,29%) cases with SDHB mutations do not have a malignancy potential according to PASS classification, 5/32 (15,63%) cases has (p=0,73). TAPPGL, HNPGL and Pheo sub-groups have a significant difference between SDHB expression (p <0,02), malignancy potential according to PASS classification (p <0,0001) and Ki-67 proliferation index (p <0,0001).
CONCLUSION
To identify patients for molecular pathological examination, routine application of SDHB immunohistochemistry to PPGL tumors are suggested especially in HNPGLs.
Topics: Head and Neck Neoplasms; Humans; Immunohistochemistry; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase; Thoracic Neoplasms
PubMed: 34181326
DOI: 10.31557/APJCP.2021.22.6.1721 -
Veterinary Medicine and Science Jul 2021Cyclooxygenase (COX) isoforms-1 and -2 have been extensively investigated in cancer. Although COX-2 is the isoform most studied and has been described in several...
Cyclooxygenase (COX) isoforms-1 and -2 have been extensively investigated in cancer. Although COX-2 is the isoform most studied and has been described in several malignancies associated with histologic criteria of malignancy and worse prognosis, COX-1 has also been linked to some forms of cancer. With the present review our aim was to summarize the current state of knowledge and clarify if and in which type of tumours COX-1 and/or COX-2 expression have real prognostic implications. We searched PubMed database for prognostic studies using predefined inclusion criteria in order to ascertain the prognostic value of COX-1 and COX-2 in malignant neoplasia in dogs and cats. Eighteen studies were analysed. COX-2 was shown to be a negative prognostic factor in canine and feline mammary tumours, canine mast cell tumour, canine melanoma, canine osteosarcoma and canine renal cell carcinoma. COX-1 showed a negative prognostic value in feline oral squamous cell carcinoma (SCC). We found high heterogeneity among studies regarding COX immunohistochemical evaluation methodology even in the same type of neoplasia pointing out the need for its standardization at least by tumour type. The available data support the use of COX-2 as a prognostic factor in canine (mammary carcinoma, mast cell tumour, melanoma, osteosarcoma and renal carcinoma) and feline (mammary carcinoma) cancers. For COX-1, its use is advised in feline oral SCC.
Topics: Animals; Cat Diseases; Cats; Cyclooxygenase 1; Cyclooxygenase 2; Dog Diseases; Dogs; Gene Expression; Prognosis
PubMed: 33751829
DOI: 10.1002/vms3.460 -
Acta Neuropsychiatrica Apr 2021The present study was designed to test the hypothesis that there is a reduction in the activity of the enzyme cytochrome c oxidase (Cox) in Alzheimer's disease (AD). (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The present study was designed to test the hypothesis that there is a reduction in the activity of the enzyme cytochrome c oxidase (Cox) in Alzheimer's disease (AD).
METHODS
Systematic review of literature and meta-analysis were used with data obtained from the PubMed, Scopus, MEDLINE, Lilacs, Eric and Cochrane. The keywords were Alzheimer's AND Cox AND mitochondria; Alzheimer's AND Cox AND mitochondria; Alzheimer's AND complex IV AND mitochondria. A total of 1372 articles were found, 23 of them fitting the inclusion criteria. The data were assembled in an Excel spreadsheet and analysed using the RevMan software. A random effects model was adopted to the estimative of the effect.
RESULTS
The data shows a significant decrease in the activity of the Cox AD patients and animal models.
CONCLUSION
Cox enzyme may be an important molecular component involved in the mechanisms underlying AD. Therefore, this enzyme may represent a possible new biomarker for the disease as a complementary diagnosis and a new treatment target for AD.
Topics: Alzheimer Disease; Animals; Colorimetry; Electron Transport Complex IV; Humans; Mice; Mitochondria; Models, Animal; Polarography; Rats; Software; Spectrophotometry
PubMed: 33256871
DOI: 10.1017/neu.2020.43 -
Cancer Chemotherapy and Pharmacology Jan 2021Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small.
METHODS
To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer).
RESULTS
Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39-2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48-0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor.
CONCLUSION
The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.
Topics: Alleles; Androgen Antagonists; Drug Resistance, Neoplasm; Humans; Male; Multienzyme Complexes; Mutation; Progesterone Reductase; Prostatic Neoplasms; Steroid 17-alpha-Hydroxylase; Steroid Isomerases; Treatment Outcome
PubMed: 33141329
DOI: 10.1007/s00280-020-04192-z -
International Journal of Molecular... Sep 2020Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of...
Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of OA-related cartilage damage. Selective COX-2 inhibitors may, next to their pain killing properties, act chondroprotective in vivo. To determine whether the route of administration is important for the efficacy of the chondroprotective properties of selective COX-2 inhibitors, a systematic review was performed according to the PRISMA guidelines. Studies investigating OA-related cartilage damage of selective COX-2 inhibitors in vivo were included. Nine of the fourteen preclinical studies demonstrated chondroprotective effects of selective COX-2 inhibitors using systemic administration. Five clinical studies were included and, although in general non-randomized, failed to demonstrate chondroprotective actions of oral selective COX-2 inhibitors. All of the four preclinical studies using bolus intra-articular injections demonstrated chondroprotective actions, while one of the three preclinical studies using a slow release system demonstrated chondroprotective actions. Despite the limited evidence in clinical studies that have used the oral administration route, there seems to be a preclinical basis for considering selective COX-2 inhibitors as disease modifying osteoarthritis drugs when used intra-articularly. Intra-articularly injected selective COX-2 inhibitors may hold the potential to provide chondroprotective effects in vivo in clinical studies.
Topics: Animals; Chondrocytes; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cytoprotection; Humans; Osteoarthritis, Knee
PubMed: 32971951
DOI: 10.3390/ijms21186962 -
Applied Immunohistochemistry &... Mar 2021Permanent, elevated expression of cyclooxygenase-2 (COX-2) in keratinocytes of epidermis can stimulate its hyperplasia and constitute a factor promoting cancer...
Permanent, elevated expression of cyclooxygenase-2 (COX-2) in keratinocytes of epidermis can stimulate its hyperplasia and constitute a factor promoting cancer development, as demonstrated in animal models. Intratumoral level and localization of COX-2 in epithelial lesions of human skin was examined immunohistochemically in 26 studies. In squamous cell carcinomas (SCCs), strong staining was observed with great compatibility. High COX-2 detectability throughout the entire tumor mass could be helpful in the finding of SCC cells. However, in basal cell carcinomas, and precancerous lesions, frequency and detection level of this protein, as well as the type and/or localization of stained cells within the tumor, varied among different research groups. The discrepancies may be due to the heterogeneity of each of these 2 groups of lesions. However, differences in COX-2 staining in normal skin indicate also possible methodological reasons. In general, COX-2 levels were significantly decreased in basal cell carcinomas compared with SCCs, which could be used in the differential diagnosis of these cancers. Reduced, although heterogenous, COX-2 expression in precancerous lesions may suggest its association with SCC development. These observations are consistent with data on the efficacy of preventive and therapeutic effects of nonsteroidal anti-inflammatory drugs that are COX-2 inhibitors.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Epithelial Cells; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Skin; Skin Neoplasms
PubMed: 32889812
DOI: 10.1097/PAI.0000000000000871 -
International Journal of Molecular... Aug 2020Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to... (Review)
Review
Despite a number of reports in the literature on the role of epigenetic mechanisms in periodontal disease, a thorough assessment of the published studies is warranted to better comprehend the evidence on the relationship between epigenetic changes and periodontal disease and its treatment. Therefore, the aim of this systematic review is to identify and synthesize the evidence for an association between DNA methylation/histone modification and periodontal disease and its treatment in human adults. A systematic search was independently conducted to identify articles meeting the inclusion criteria. DNA methylation and histone modifications associated with periodontal diseases, gene expression, epigenetic changes after periodontal therapy, and the association between epigenetics and clinical parameters were evaluated. Sixteen studies were identified. All included studies examined DNA modifications in relation to periodontitis, and none of the studies examined histone modifications. Substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology, was found. There was some evidence, albeit inconsistent, for an association between DNA methylation and periodontal disease. , , , , , and were identified as candidate genes that have been assessed for DNA methylation in periodontitis. While several included studies found associations between methylation levels and periodontal disease risk, there is insufficient evidence to support or refute an association between DNA methylation and periodontal disease/therapy in human adults. Further research must be conducted to identify reproducible epigenetic markers and determine the extent to which DNA methylation can be applied as a clinical biomarker.
Topics: Cyclooxygenase 2; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Genetic Markers; Histone Code; Histones; Humans; Interferon-gamma; Interleukin-6; Periodontal Diseases; Receptors, Interleukin-6; Suppressor of Cytokine Signaling 1 Protein; Tumor Necrosis Factor-alpha
PubMed: 32867386
DOI: 10.3390/ijms21176217 -
Molecules (Basel, Switzerland) Jul 2020Microalgae productive chains are gaining importance as sustainable alternatives to obtain natural pigments. This work presents a review on the most promising pigments...
Microalgae productive chains are gaining importance as sustainable alternatives to obtain natural pigments. This work presents a review on the most promising pigments and microalgal sources by gathering trends from a 10-year bibliometric survey, a patents search, and an industrial and market analysis built from available market reports, projects and companies' webpages. The performed analysis pointed out chlorophylls, phycocyanin, astaxanthin, and β-carotene as the most relevant pigments, and , , , and , respectively, as the most studied sources. is referred in the highest number of patents, corroborating a high technological interest in this microalga. The biorefinery concept, investment in projects and companies related to microalgae cultivation and/or pigment extraction is increasingly growing, particularly, for phycocyanin from . These pieces of evidence are a step forward to consolidate the microalgal pigments market, which is expected to grow in the coming years, increasing the prospects of replacing synthetic pigments by natural counterparts.
Topics: Drug Industry; Microalgae; Phycocyanin; Pigments, Biological
PubMed: 32731380
DOI: 10.3390/molecules25153406