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International Journal of Molecular... Jul 2022Ovarian cancer is the most lethal gynecologic malignancy in the United States. Some patients affected by ovarian cancers often present genome instability with one or... (Review)
Review
Ovarian cancer is the most lethal gynecologic malignancy in the United States. Some patients affected by ovarian cancers often present genome instability with one or more of the defects in DNA repair pathways, particularly in homologous recombination (HR), which is strictly linked to mutations in breast cancer susceptibility gene 1 (BRCA 1) or breast cancer susceptibility gene 2 (BRCA 2). The treatment of ovarian cancer remains a challenge, and the majority of patients with advanced-stage ovarian cancers experience relapse and require additional treatment despite initial therapy, including optimal cytoreductive surgery (CRS) and platinum-based chemotherapy. Targeted therapy at DNA repair genes has become a unique strategy to combat homologous recombination-deficient (HRD) cancers in recent years. Poly (ADP-ribose) polymerase (PARP), a family of proteins, plays an important role in DNA damage repair, genome stability, and apoptosis of cancer cells, especially in HRD cancers. PARP inhibitors (PARPi) have been reported to be highly effective and low-toxicity drugs that will tremendously benefit patients with HRD (i.e., BRCA 1/2 mutated) epithelial ovarian cancer (EOC) by blocking the DNA repair pathways and inducing apoptosis of cancer cells. PARP inhibitors compete with NAD at the catalytic domain (CAT) of PARP to block PARP catalytic activity and the formation of PAR polymers. These effects compromise the cellular ability to overcome DNA SSB damage. The process of HR, an essential error-free pathway to repair DNA DSBs during cell replication, will be blocked in the condition of BRCA 1/2 mutations. The PARP-associated HR pathway can also be partially interrupted by using PARP inhibitors. Grossly, PARP inhibitors have demonstrated some therapeutic benefits in many randomized phase II and III trials when combined with the standard CRS for advanced EOCs. However, similar to other chemotherapy agents, PARP inhibitors have different clinical indications and toxicity profiles and also face drug resistance, which has become a major challenge. In high-grade epithelial ovarian cancers, the cancer cells under hypoxia- or drug-induced stress have the capacity to become polyploidy giant cancer cells (PGCCs), which can survive the attack of chemotherapeutic agents and start endoreplication. These stem-like, self-renewing PGCCs generate mutations to alter the expression/function of kinases, p53, and stem cell markers, and diploid daughter cells can exhibit drug resistance and facilitate tumor growth and metastasis. In this review, we discuss the underlying molecular mechanisms of PARP inhibitors and the results from the clinical studies that investigated the effects of the FDA-approved PARP inhibitors olaparib, rucaparib, and niraparib. We also review the current research progress on PARP inhibitors, their safety, and their combined usage with antiangiogenic agents. Nevertheless, many unknown aspects of PARP inhibitors, including detailed mechanisms of actions, along with the effectiveness and safety of the treatment of EOCs, warrant further investigation.
Topics: Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Clinical Trials, Phase II as Topic; Female; Genes, BRCA2; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Randomized Controlled Trials as Topic
PubMed: 35897700
DOI: 10.3390/ijms23158125 -
Exploring and exploiting genetics and genomics for sweetpotato improvement: Status and perspectives.Plant Communications Sep 2022Sweetpotato (Ipomoea batatas (L.) Lam.) is one of the most important root crops cultivated worldwide. Because of its adaptability, high yield potential, and nutritional... (Review)
Review
Sweetpotato (Ipomoea batatas (L.) Lam.) is one of the most important root crops cultivated worldwide. Because of its adaptability, high yield potential, and nutritional value, sweetpotato has become an important food crop, particularly in developing countries. To ensure adequate crop yields to meet increasing demand, it is essential to enhance the tolerance of sweetpotato to environmental stresses and other yield-limiting factors. The highly heterozygous hexaploid genome of I. batatas complicates genetic studies and limits improvement of sweetpotato through traditional breeding. However, application of next-generation sequencing and high-throughput genotyping and phenotyping technologies to sweetpotato genetics and genomics research has provided new tools and resources for crop improvement. In this review, we discuss the genomics resources that are available for sweetpotato, including the current reference genome, databases, and available bioinformatics tools. We systematically review the current state of knowledge on the polyploid genetics of sweetpotato, including studies of its origin and germplasm diversity and the associated mapping of important agricultural traits. We then outline the conventional and molecular breeding approaches that have been applied to sweetpotato. Finally, we discuss future goals for genetic studies of sweetpotato and crop improvement via breeding in combination with state-of-the-art multi-omics approaches such as genomic selection and gene editing. These approaches will advance and accelerate genetic improvement of this important root crop and facilitate its sustainable global production.
Topics: Genomics; High-Throughput Nucleotide Sequencing; Ipomoea batatas; Plant Breeding; Polyploidy
PubMed: 35643086
DOI: 10.1016/j.xplc.2022.100332 -
Prenatal Diagnosis Jun 2023To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations.
METHOD
We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2.
RESULTS
Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61-9.95], I of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07-6.47], I = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34-14.78], I = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83-134.68], I = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76-2.03], I = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78-9.00], I = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed.
CONCLUSION
An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations.
Topics: Pregnancy; Female; Humans; Trisomy 18 Syndrome; Trisomy 13 Syndrome; Turner Syndrome; Triploidy; Cell-Free Nucleic Acids; Prenatal Diagnosis; Down Syndrome
PubMed: 37143173
DOI: 10.1002/pd.6366 -
Science China. Life Sciences Jan 2019Hybridization is widely used. However, for a long time, systematic theories and technologies related to hybridization in fish have been lacking. In this study, through...
Hybridization is widely used. However, for a long time, systematic theories and technologies related to hybridization in fish have been lacking. In this study, through long-term systematic research, we investigated and obtained the main rules regarding inheritance and reproduction related to fish distant hybridization. Furthermore, we established one-step and multistep breeding technologies that were suitable for interspecific hybridization and intraspecific hybridization. Simultaneously, we used these two breeding technologies to produce a batch of diploid fish lineages and tetraploid fish lineages and improved fishes. In addition, we widely discuss the methods, technologies and results of hybridization breeding, referring to the domestic and foreign literature on fish hybridization. We hope that this paper will be beneficial for the research and application of fish hybrid breeding.
Topics: Animals; Breeding; Diploidy; Female; Fishes; Hybridization, Genetic; Male; Ploidies; Reproduction; Tetraploidy
PubMed: 30554295
DOI: 10.1007/s11427-018-9408-x -
Leukemia & Lymphoma Jan 2021The prognostic significance and optimal management of tetraploidy/near-tetraploidy acute myeloid leukemia (T/NT AML) remains unclear given its limited data. This is... (Review)
Review
The prognostic significance and optimal management of tetraploidy/near-tetraploidy acute myeloid leukemia (T/NT AML) remains unclear given its limited data. This is especially true after factoring in additional chromosomal alterations, which carry their own prognostic weight. Here, we analyze 128 cases of T/NT in AML from the literature along with two additional cases, which is the largest review of this subject to date. Based on our retrospective analysis, we found that regardless of the risk status attributed to cytogenetics, the prognosis of tetraploid or near-tetraploid AML is dismal and should be incorporated within the unfavorable risk group. Complete remission is paramount to survival in this population. Specific induction protocols for high-risk AML appear to have higher rates of complete remission in the T/NT AML population. Moreover, longer overall survival can be achieved with chemotherapy followed by allogeneic stem cell transplantation at first complete remission.
Topics: Humans; Leukemia, Myeloid, Acute; Prognosis; Remission Induction; Retrospective Studies; Tetraploidy
PubMed: 32993375
DOI: 10.1080/10428194.2020.1817435 -
Frontiers in Plant Science 2024The Brassicaceae is a worldwide family that produces ornamental flowers, edible vegetables, and oilseed plants, with high economic value in agriculture, horticulture,...
The Brassicaceae is a worldwide family that produces ornamental flowers, edible vegetables, and oilseed plants, with high economic value in agriculture, horticulture, and landscaping. This study used the Web of Science core dataset and the CiteSpace bibliometric tool to quantitatively visualize the number of publications, authors, institutions, and countries of 3139 papers related to Brassicaceae plants from 2002 to 2022. The keywords and references were divided into two phases: Phase 1 (2002-2011) and Phase 2 (2012-2022) for quantitative and qualitative analysis. The results showed: An average annual publication volume of 149 articles, with an overall fluctuating upward trend; the research force was mainly led by Professor Ihsan A. Al-shehbaz from Missouri Botanical Garden; and the United States had the highest number of publications. In the first phase, research focused on the phylogeny of Brassicaceae plants, while the second phase delved into diverse research based on previous studies, research in areas such as polyploidy, molecular technique, physiology, and hyperaccumulator has been extended. Based on this research, we propounded some ideas for future studies on Brassicaceae plants and summarized the research gaps.
PubMed: 38357268
DOI: 10.3389/fpls.2024.1285050 -
Ecology Letters Nov 2014The hypothesis that interspecific hybridisation promotes invasiveness has received much recent attention, but tests of the hypothesis can suffer from important... (Meta-Analysis)
Meta-Analysis Review
The hypothesis that interspecific hybridisation promotes invasiveness has received much recent attention, but tests of the hypothesis can suffer from important limitations. Here, we provide the first systematic review of studies experimentally testing the hybridisation-invasion (H-I) hypothesis in plants, animals and fungi. We identified 72 hybrid systems for which hybridisation has been putatively associated with invasiveness, weediness or range expansion. Within this group, 15 systems (comprising 34 studies) experimentally tested performance of hybrids vs. their parental species and met our other criteria. Both phylogenetic and non-phylogenetic meta-analyses demonstrated that wild hybrids were significantly more fecund and larger than their parental taxa, but did not differ in survival. Resynthesised hybrids (which typically represent earlier generations than do wild hybrids) did not consistently differ from parental species in fecundity, survival or size. Using meta-regression, we found that fecundity increased (but survival decreased) with generation in resynthesised hybrids, suggesting that natural selection can play an important role in shaping hybrid performance - and thus invasiveness - over time. We conclude that the available evidence supports the H-I hypothesis, with the caveat that our results are clearly driven by tests in plants, which are more numerous than tests in animals and fungi.
Topics: Animals; Fertility; Fungi; Hybridization, Genetic; Introduced Species; Phylogeny; Plants; Selection, Genetic
PubMed: 25234578
DOI: 10.1111/ele.12355 -
Annals of Botany Aug 2020Whole-genome duplication is known to influence ecological interactions and plant physiology; however, despite abundant case studies, much is still unknown about the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Whole-genome duplication is known to influence ecological interactions and plant physiology; however, despite abundant case studies, much is still unknown about the typical impact of genome duplication on plant secondary metabolites (PSMs). In this study, we assessed the impact of polyploidy events on PSM characteristics in non-cultivated plants.
METHODS
We conducted a systematic review and meta-analysis to compare composition and concentration of PSMs among closely related plant species or species complexes differing in ploidy level.
KEY RESULTS
We assessed 53 studies that focus on PSMs among multiple cytotypes, of which only 14 studies compared concentration quantitatively among cytotypes. We found that whole-genome duplication can have a significant effect on PSM concentration; however, these effects are highly inconsistent.
CONCLUSION
Overall, there was no consistent effect of whole-genome duplication on PSM concentrations or profiles.
Topics: Gene Duplication; Genome, Plant; Humans; Plants; Ploidies; Polyploidy
PubMed: 32504537
DOI: 10.1093/aob/mcaa107