Colorectal cancer (CRC) results from the progressive accumulation of multiple genetic and epigenetic aberrations within cells. The progression from colorectal adenoma to carcinoma is caused by three ...major pathways: Microsatellite instability, chromosomal instability and CpG island methylator phenotype. A growing body of scientific evidences suggests that CRC is a heterogeneous disease, and genetic characteristics of the tumors determine their prognostic outcome and response to targeted therapies. Early diagnosis and effective targeted therapies based on a current knowledge of the molecular characteristics of CRC are essential to the successful treatment of CRC. Therefore, the present review summarized the current understanding of the molecular characteristics of CRC, and discussed its implications for diagnosis and targeted therapy.
Radiotherapy (RT) followed by radical surgery is an effective standard treatment strategy for various types of cancer, including rectal cancer. The response to RT varies among patients, and the ...radiosensitivity of cancer cells determines the clinical outcome of patients. However, the application of RT to patients with radioresistant tumors may result in radiation-induced toxicity without clinical benefits. Currently, there are no effective methods to predict the response to RT. The limitations of the methods currently used to evaluate tumor radiosensitivity, which are mainly based on clinical and radiological features, are low sensitivity and specificity. Non-coding RNAs (ncRNAs) have emerged as a class of biomarkers for predicting radiosensitivity. In particular, the expression pattern of ncRNAs can predict the response to RT in patients with rectal cancer. Thus, ncRNAs may be used as potential biomarkers and therapeutic targets to improve the diagnosis and treatment outcome of patients with rectal cancer. In the present review, the current knowledge on the limitations of RT for rectal cancer and the association between ncRNA expression and sensitivity of rectal cancer to RT are presented. Additionally, the potential of ncRNAs as predictive biomarkers and therapeutic targets to mitigate resistance of rectal cancer to RT is discussed.
Human papillomavirus (HPV) infection in men is a serious issue because it is associated with genital warts, anogenital cancers, and HPV transmission to their sex partners. This study aimed to ...investigate the prevalence and genotypes of HPVs in Vietnamese male patients hospitalized with sexually transmitted infection (STI) symptoms between 2016 and 2020 by using polymerase chain reaction and reverse dot blot hybridization analysis. HPV DNA was detected in 191/941 (20.3%) penile cell samples. The HPV patient's mean age was 30.3 in the range of 16‐ and 69‐year‐old. The highest HPV prevalence (84.7%) was found in patients between 20‐ and 39‐year‐old. A total of 313 HPV genotypes were identified. The multiple‐infection rate was 42.9%. The most common high‐risk (HR)‐HPV genotypes were HPV‐16 (8.0%), HPV‐51 (7.7%), HPV‐52 (4.8%), HPV‐56 (4.2%), and HPV‐18 (3.8%). Furthermore, HPV‐11 and HPV‐6 genotypes were the two most common low‐risk (LR)‐HPV genotypes with the rate of 36.7% and 21.4%, respectively. Notably, HPV‐52 was found circulating in Vietnam for the first time. In conclusion, this study results showed that HPV prevalence in Vietnamese male patients was common and diverse. In addition, regarding public health and cancer prevention, the inclusion of the HPV vaccination into the national vaccination program for both men and women is recommended.
Highlights
This study reports the infection of HPVs in Vietnamese male patients hospitalized with STI symptoms was common and diverse. Regarding public health and cancer prevention, we recommend the use of HPV vaccination into the national vaccination program for both men and women.
Prolonged cell survival occurs through the expression of specific protein isoforms generated by alternate splicing of mRNA precursors in cancer cells. How alternate splicing regulates tumor ...development and resistance to targeted therapies in cancer remain poorly understood. Here we show that RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. RNF113A is a RNA-binding protein which regulates the splicing of multiple candidates involved in cell survival. RNF113A deficiency triggers cell death upon DNA damage through multiple mechanisms, including apoptosis via the destabilization of the prosurvival protein MCL-1, ferroptosis due to enhanced SAT1 expression, and increased production of ROS due to altered Noxa1 expression. RNF113A deficiency circumvents the resistance to Cisplatin and to BCL-2 inhibitors through the destabilization of MCL-1, which thus defines spliceosome inhibitors as a therapeutic approach to treat tumors showing acquired resistance to specific drugs due to MCL-1 stabilization.
One-step thermal treatment homogeneous blends of PVA, citric acid, and ethylenediamine results in composites that emit intensively under UV bumping. The origin of absorption, excitation and emission ...properties of composites was investigated by combining optical and chemical characterizations. It has been demonstrated that IPCA, being involved in diverse structures accounts for the optical properties of composites.
Display omitted
•The synthesis of highly photoluminescent PVA composites is presented.•One step thermal annealing enables conversion of molecular precursors into fluorophores.•Chemical structure of fluorophores is identified.•IPCA involved in diverse structures dominates the optical properties of composites.
There is a strong demand for developing a simple, scalable, and transferable method to prepare homogeneous and highly photoluminescent composite for diverse applications. Herein, homogeneous composites were successfully synthesized by thermal annealing blends of polyvinyl alcohol, citric acid, and ethylenediamine. The composites exhibited intensive photoluminescence under excitation around 350 nm. Infrared, nuclear resonance, and optical characterizations suggest that diverse structures involving 5-oxo-1,2,3,5-tetrahydroimidazo-1,2-α-pyridine-7-carboxylic acid (IPCA) accounts for the high photoluminescence of the composites.
RNA therapeutics for β-thalassemia Duong, Hong-Quan; Nguyen, Thi-Hue; Hoang, Minh-Cong ...
Progress in molecular biology and translational science,
2024, Letnik:
204
Journal Article
Recenzirano
β-thalassemia is an autosomal recessive disease, caused by one or more mutations in the β-globin gene that reduces or abolishes β-globin chain synthesis causing an imbalance in the ratio of α- and ...β-globin chain. Therefore, the ability to target mutations will provide a good result in the treatment of β-thalassemia. RNA therapeutics represents a promising class of drugs inclusive antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and APTAMER have investigated in clinical trials for treatment of human diseases as β-thalassemia; Especially, ASO therapeutics can completely treat β-thalassemia patients by the way of making ASO infiltrating through erythrocyte progenitor cells, migrating to the nucleus and hybridizing with abnormal splicing sites to suppress an abnormal splicing pattern of β-globin pre-mRNA. As a result, the exactly splicing process is restored to increase the expression of β-globin which increases the amount of mature hemoglobin of red blood cells of β-thalassemia patients. Furthermore, current study demonstrates that RNA-based therapeutics get lots of good results for β-thalassemia patients. Then, this chapter focuses on current advances of RNA-based therapeutics and addresses current challenges with their development and application for treatment of β-thalassemia patients.
Axial bearing capacity of piles is the most important parameter in pile foundation design. In this paper, artificial neural network (ANN) and random forest (RF) algorithms were utilized to predict ...the ultimate axial bearing capacity of driven piles. An unprecedented database containing 2314 driven pile static load test reports were gathered, including the pile diameter, length of pile segments, natural ground elevation, pile top elevation, guide pile segment stop driving elevation, pile tip elevation, average standard penetration test (SPT) value along the embedded length of pile, and average SPT blow counts at the tip of pile as input variables, whereas the ultimate load on pile top was considered as output variable. The dataset was divided into the training (70%) and testing (30%) parts for the construction and validation phases, respectively. Various error criteria, namely mean absolute error (MAE), root mean squared error (RMSE), and the coefficient of determination (R2) were used to evaluate the performance of RF and ANN algorithms. In addition, the predicted results of pile load tests were compared with five empirical equations derived from the literature and with classical multi-variable regression. The results showed that RF outperformed ANN and other methods. Sensitivity analysis was conducted to reveal that the average SPT value and pile tip elevation were the most important factors in predicting the axial bearing capacity of piles.
Non-small cell lung cancer (NSCLC) is the most common cancer worldwide, which is related with poor prognosis and resistance to chemotherapy. Notably, ruthenium-based complexes have emerged as good ...alternative to the currently used platinum-based drugs for cancer therapy. In the present study, we synthesized a novel bis-pyrimidine based ligand 1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene (L) and used it in the synthesis of a dimetallic Ru(II) cymene complex (Ru(η6-p-cymene)Cl)2(1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene) (L-Ru). We checked the stability of this complex in solution state in D2O/DMSO‑d6 mixture and found it to be highly stable under these conditions. We determined the anticancer activity and mechanism of action of L-Ru in human NSCLC A549 and A427 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and related biological analyses. These results revealed that L-Ru exerted a strong inhibitory effect on the cells proliferation,G0/G1-arrest, accompanied with upregulation of p53, p21, p15, cleaved Poly (ADP-ribose) polymerase (PARP) protein and downregulation of cell cycle markers. L-Ru inhibited cell migration and invasion. The mitochondria-mediated apoptosis of NSCLC induced by L-Ru was also observed followed by the increase of apoptosis regulator B-cell lymphoma 2 associated X (BAX), and activation of caspase-3/-9. The effects of L-Ru on the cell viability, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells and Annexin V-positive cells apoptosis induction were remarkably attenuated. This complex induced DNA damage, cell cycle arrest and cell death via caspase-dependent apoptosis involving PARP activation and induction of p53-dependent pathway. These findings suggested that this ruthenium complex might be a potential effective chemotherapeutic agent in NSCLC therapy.
bis-Pyrimidine ligand based dimetallic Ru(II)cymene complex (Ru(η6-p-cymene)Cl)2(1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene) was prepared and characterized. Its stability was determined by 1H NMR spectroscopy. This complex showed potential in vitro anticancer effect, mechanistically it upregulated p53, p21, p15, cleaved Poly (ADP-ribose) polymerase protein, downregulated cell cycle markers and induced other apoptotic pathways. Display omitted
•bis-Pyrimidine based dimetallic Ru(II)(η6-p-cymene) complex•p53-Dependent pathway activation•Inhibition of cell migration and invasion•Apoptosis genes activation•Cell cycle arrest by metal complex
Pancreatic cancer remains an intractable cancer with a poor five-year survival rate, which requires new therapeutic modalities based on the biology of pancreatic oncogenesis. Nuclear factor E2 ...related factor-2 (NRF2), a key cytoprotective nuclear transcription factor, regulates antioxidant production, reduction, detoxification and drug efflux proteins. It also plays an essential role in cell homeostasis, cell proliferation and resistance to chemotherapy. We aimed to evaluate the possibility that modulation of NRF2 expression could be effective in the treatment of pancreatic cancer cells. We investigated whether the depletion of NRF2 by using small interfering RNAs (siRNAs) is effective in the expression of biomarkers of pancreatic cancer stemness such as aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) and aldehyde dehydrogenase 3 family, member A1 (ALDH3A1). NRF2 knockdown markedly reduced the expression of NRF2 and glutamate-cysteine ligase catalytic subunit (GCLC) in cell lines established from pancreatic cancers. NRF2 silencing also decreased the ALDH1A1 and ALDH3A1 expression. Furthermore, this NRF2 depletion enhanced the antiproliferative effects of the chemotherapeutic agent, 5-fluorouracil (5-FU) in pancreatic cancer cells.
A series of bis-salicylaldimine ligands bearing two ON-donor functions were reacted with dichloro(p-cymene)ruthenium(II) dimer in the presence of base (NaOAc) and a series of four dimetallic Ru(II) ...arene complexes (Ru(p-cymene))2(bis-salicylaldimine)Cl2 (C1C4) were prepared. These complexes were obtained in excellent isolated yields and characterized in detail by using different spectroscopic techniques. The structure of C1 was also determined in solid state by single crystal X-ray analysis. These complexes were studied for their cytotoxic effect against three different types of human cancer cells including hepatocellular carcinoma (HepG2), non-small-cell lung cancer (A549) and breast cancer (MCF-7) cells by MTT assay. These complexes showed considerable cytotoxic effect in all the above-mentioned cell lines that was comparable to the effect of cisplatin. C1 and C2 showed moderate anticancer effect while C3 and C4 showed reasonable cytotoxicity. We found the cytotoxicity was increased in series from C1 to C4 representing the effect of ligand modification from small to bulky group at the amine functionality of the salicylaldimine. We selected C3 and C4 for mechanistic anticancer study in MCF-7 cells. The acridine orange/ethidium bromide and DAPI staining assays of MCF-7 cells treated with Ru(II) complexes showed apoptosis in cancer cells. Similarly, these complexes induced p53 protein expression in MCF-7 cells. Further, increased mRNA levels of p63, p73, PUMA, BAX and NOXA genes were observed in response to the treatment with C3 and C4, while cyclinD1, MMP3 and ID1 gene expression was significantly reduced. We found reduced invasion ability in breast cancer cells treated with C3 and C4. Taken together, we demonstrated that bis-salicylaldimine based dimetallic Ru-(p-cymene) complexes exerts anticancer effects by p53 pathway, suggesting the promising chemotherapeutic potentials of these Ru(II) complexes for the treatment of cancer. This study may further pave for their in depth in vitro or in vivo anticancer investigations.
Dimetallic bis-salicylaldimine based Ru(II) arene complexes (Ru (p-cymene))2 (bis-salicylaldime)Cl2 were prepared and investigated as anticancer agents. Their in vitro cytotoxic effect on cancer cells was comparable to cisplatin. They induced p53, p63 and p73 genes expression and regulated PUMA, BAX and NOXA genes in MCF-7 breast cancer cells. Display omitted
•Dimetallic ruthenium complexes.•Single crystal X-ray structure characterization.•Anticancer study of Ru(II) arene complexes.•Genes activation for efficient apoptosis in cancer cell.•p53 activation by Ru(II) complexes.
PDF
