Pharmaceutical Science Advances最新文献

{"title":"Nanodispersion of lutein with use of metastable polymorph for improved dissolution and oral absorption","authors":"Kodai Ueno,&nbsp;Monami Sugihara,&nbsp;Tetsuya Matsushita,&nbsp;Kohei Yamada,&nbsp;Hideyuki Sato,&nbsp;Satomi Onoue","doi":"10.1016/j.pscia.2025.100067","DOIUrl":"10.1016/j.pscia.2025.100067","url":null,"abstract":"<div><div>Lutein (LT) is an attractive nutrient for eye health, although it has low water solubility and poor oral absorption. The present study aimed to develop a novel nanodispersion (ND) of LT using a metastable polymorph, offering improved oral absorption of LT. A metastable crystalline form of LT (LT-II) and hydroxypropyl cellulose were subjected to wet-milling followed by freeze-drying to obtain the ND of LT-II (ND/LT-II), and its physicochemical, photochemical, and pharmacokinetic properties of LT samples were evaluated. The mean particle size of LT-II in ND/LT-II was 354 ​nm, and there was no significant change in the crystalline form of LT-II, even after wet milling and freeze-drying. LT generated significant amounts of superoxide anions upon exposure to pseudo-sunlight (250 ​W/m²), indicating high photoreactivity. After irradiation with pseudo-sunlight (250 ​W/m², 30 ​min), the percentages of LT remaining in the LT solution, amorphous LT, and ND/LT-II were 75, 79, and 92%, respectively. LT-II dissolved slightly faster than the stable crystalline form of LT (LT-I) in the dissolution media. ND/LT-II further improved the dissolution property of LT-II, and the dissolved amount of LT was 137- and 7.2-fold higher than that of LT-I and LT-II, respectively, at 2 ​h after dispersion in water. After administration of LT samples (100 ​mg-LT/kg), systemic exposure to LT in the LT-I and LT-II was negligible, whereas a marked improvement in oral absorption was observed in the ND/LT-II groups. Thus, applying ND technology to LT-II may improve oral absorption, and thus the nutrient function of LT.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and characterization of tadalafil-loaded hydrogel: An in-vivo evaluation of wound healing activity","authors":"Anita Sadat Haji Seyed Javadi Pajouhi ,&nbsp;Amir Larki-Harcheghani ,&nbsp;Mojdeh Mohammadi ,&nbsp;Sajjad Makhdoomi ,&nbsp;Alireza Nourian ,&nbsp;Katayoun Derakhshandeh","doi":"10.1016/j.pscia.2025.100066","DOIUrl":"10.1016/j.pscia.2025.100066","url":null,"abstract":"<div><div>Tadalafil (TD) is a phosphodiesterase type 5 (PDE-5) inhibitor that has gained attention for its wound healing properties. In this study, a TD-loaded hydrogel was prepared and characterized, and its wound-healing efficacy was evaluated. After preparing the TD hydrogel, its physicochemical properties such as viscosity, pH, drug-loading capacity (DL%), <em>in vitro</em> release behavior, and stability were characterized. Moreover, <em>in vivo</em> studies were performed to evaluate hydroxyproline (HP) and the wound healing efficacy of 1, 1.5, 3% (w/w) TD hydrogels in New Zealand rabbits. Histopathological analysis was also performed using hematoxylin and eosin (H&amp;E) staining. We successfully prepared a TD hydrogel with high stability. The results of the <em>in vivo</em> experiments on full-thickness wounds showed that the 1.5% TD hydrogel with a pH of 5.81 ​± ​0.421, viscosity of 12,435 ​± ​63, drug-loading capacity of 91.73 ​± ​1.482%, and drug release rate of 88% was superior to other formulations when HP level was increased, which decreased the time required for wound healing; this was corroborated by the histological analysis. Thus, the TD hydrogel formulation prepared in this study is a promising topical therapeutic agent for wound healing.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Garcioligantone J and K, a pair of epimeric caged-polyprenylated xanthonoids from Garcinia Oligantha, inhibit the growth of lung cancer cells through ER stress-mediated apoptosis","authors":"Lingyu Li ,&nbsp;Hao Zheng ,&nbsp;Qingying Liu ,&nbsp;Dongmei Ren","doi":"10.1016/j.pscia.2025.100065","DOIUrl":"10.1016/j.pscia.2025.100065","url":null,"abstract":"<div><div>Garcioligantone J and K (GLJ and GLK) are a pair of isomers isolated from <em>Garcinia Oligantha</em> Merr. Herein, we described the structure elucidation including the absolute configurations of GLJ and GLK, explored and compared their anti-cancerous effects and underlying mechanism in A549 and NCI-H292 ​cells. The results indicated that GLJ and GLK are two isomers with different configuration at C-12, they inhibited cell proliferation and induced apoptosis in two lung cancer cell lines with almost the same extent. The induction of apoptosis by GLJ and GLK was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed increased Bax/Bcl-2 ratio, cleaved caspase-3, caspase-9 and PARP, loss of mitochondrial membrane potential (MMP) in cells, indicating that GLJ and GLK induced mitochondrial apoptosis. Increased GRP78, p-eIF2α and GADD153 manifested that endoplasmic reticulum (ER) stress was induced by GLJ and GLK. Meanwhile, upregulated reactive oxygen species (ROS) level was found and GLJ and GLK-induced ER stress and apoptosis could be attenuated by ROS scavenger NAC. Apoptosis induced by GLJ and GLK also could be alleviated by ER stress inhibitor 4-PBA. These showed that GLJ and GLK-induced apoptosis was mediated by ER stress relied on ROS generation. The efficacy of GLJ and GLK on lung cancer cell proliferation was further demonstrated in a zebrafish xenograft model. Collectively, the absolute configurations of GLJ and GLK were identified and they exerted lethal effects on lung cancer cells to the same extent via ROS-ER stress-mitochondrial apoptosis signaling, suggesting that GLJ and GLK might be used as potential modulating agents in lung cancer treatments.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-walled carbon nanotubes sensors: Preparation and bio-application advances","authors":"Xiaotong Chen ,&nbsp;Difan Wang ,&nbsp;Wenshuo Ding ,&nbsp;Hengchang Zang,&nbsp;Lian Li","doi":"10.1016/j.pscia.2025.100064","DOIUrl":"10.1016/j.pscia.2025.100064","url":null,"abstract":"<div><div>Molecular recognition and detection are the main concerns in the field of biological analysis because they can be affected by various factors. Single-walled carbon nanotube (SWCNTs)-based optical biosensors have been applied in this field owing to their high sensitivity, good fluorescence stability, and tissue transparency. Purification of single-chiral SWCNTs and surface functionalization of SWCNTs are effective strategies for achieving real-time monitoring and high-throughput screening of biological analytes. Combining these technologies with microfluidic platforms and machine learning algorithms further broadens the application areas of sensors and enhances their analytical performance and usefulness in complex biological systems. Therefore, this review first discusses the preparation methods for single-chiral SWCNTs in recent years and introduces covalent and non-covalent functionalization techniques for SWCNTs, including oligonucleotide chains, peptides, and surfactant modifications. Subsequently, we systematically evaluate the applications of functionalized SWCNT biosensors for recognizing small molecules, including gas phase composition, neurotransmitters, and reactive oxygen species. These biosensors have been shown to have high sensitivity and specificity in the detection of a wide range of small molecules, offering a wide range of possibilities for analyzing volatile organic compounds, signaling molecules, and reactive oxygen species within biological systems, and providing new ways of gaining insights into the complex mechanisms of disease progression. Finally, we have analyzed the ability of SWCNT biosensors to recognize biomolecules in various categories, including proteins, nucleic acids, and lipids. Using these sensors for clinical disease diagnosis improves the accuracy and timeliness of diagnosis and opens up new ways to improve patients' prognosis and quality of life. We believe that SWCNT biosensors have great potential for future development in biomedicine.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects and metabolomics analysis of dihydromyricetin on cyclophosphamide-induced hepatotoxicity in mice","authors":"Fei Teng,&nbsp;Haina Wang","doi":"10.1016/j.pscia.2025.100063","DOIUrl":"10.1016/j.pscia.2025.100063","url":null,"abstract":"<div><div>Cyclophosphamide (CTX) is a chemotherapeutic agent with cytotoxic and immunosuppressive activity. It is used to treat a wide variety of cancers and autoimmune diseases. However, side effects caused by its toxic metabolites, especially hepatotoxicity, limit its clinical application. The natural dihydroflavonol compound dihydromyricetin (DHM) has anticancer, anti-inflammatory, and antioxidant properties. This study aimed to evaluate the protective effects of DHM against CTX-induced hepatotoxicity in mice. Male ICR mice were pretreated with DHM (100, 200, and 400 ​mg/kg b.w.) orally before intraperitoneal injection with CTX (100 ​mg/kg b.w.) for 7 days. The mice were then sacrificed to analyze biochemical and histological parameters as well as metabolomics profiles. DHM ameliorated CTX-induced elevations in the liver index, alanine aminotransferase, aspartate transaminase, and malondialdehyde levels, and pathological changes and increased levels of glutathione and antioxidant enzymes, such as superoxide dismutase and catalase. Based on a KEGG pathway analysis of altered serum and liver metabolites, OXPHOS may play an important role in the observed protective effects. Further analysis revealed that DHM increased the activity of Na⁺-K⁺-ATPase in mice, which affected CTX-induced mitochondrial energy metabolism. To conclude, DHM protected against CTX-induced hepatotoxicity, possibly through reducing oxidative stress and regulating energy metabolism, providing a potential strategy for treatment and prevention.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sample preparation of Hedyotis diffusa Willd. for two-dimensional gas chromatography-time of flight mass spectroscopic analysis enhanced chemical profiling","authors":"Duxin Li ,&nbsp;Xinying Du ,&nbsp;Wanru Bai ,&nbsp;Oliver J. Schmitz","doi":"10.1016/j.pscia.2024.100056","DOIUrl":"10.1016/j.pscia.2024.100056","url":null,"abstract":"<div><div><em>Hedyotis diffusa</em> Willd., a herbal remedy for cancer, has a complex chemical profile that is difficult to analyze in detail. Here, we introduce an optimized sample preparation method coupled with two-dimensional gas chromatography-time-of-flight mass spectrometry (GC ​× ​GC-TOF/MS) to enhance the chemical profiling of <em>H. diffusa</em>. By employing dichloromethane extraction for nonpolar compounds, aqueous extraction, and solid-phase extraction fractionation into moderately polar and polar fractions, we extracted and analyzed a comprehensive range of chemicals from <em>H. diffusa</em>. GC ​× ​GC-TOF/MS analysis revealed a rich chemical landscape, identifying 185, 325, and 483 peaks in the dichloromethane extract, solid-phase extraction elution, and unretained fractions, respectively. Library matching against known compounds confirmed 155, 178, and 184 hits with a similarity of 80% or greater. Notably, this method also involves group-type elution of steroids and anthraquinones, facilitating the identification and screening of similar compounds. This comprehensive approach to herbal chemical analysis offers a high-dimensional perspective and greatly advances our understanding of the chemical constituents of <em>H. diffusa</em>.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin inhibits malignant progression of high metastatic advanced colon cancer in hypoxia via suppressing ROS and PI3K/AKT pathway","authors":"Pengfei Shang ,&nbsp;Jiawei Yang ,&nbsp;Lijun Shao ,&nbsp;Chao Sun ,&nbsp;Jianbo Ji ,&nbsp;Xiaoyan Wang ,&nbsp;Zongxue Zheng ,&nbsp;Xiuli Guo","doi":"10.1016/j.pscia.2024.100057","DOIUrl":"10.1016/j.pscia.2024.100057","url":null,"abstract":"<div><div>Advanced metastatic colon cancer is difficult to treat with existing chemotherapy medicines, and hypoxic microenvironment is closely related to angiogenesis and distant metastasis of colon cancer. Quercetin, a natural flavonoid, has been shown anti-tumor effects. The aim of this study is to investigate the effect of quercetin alone or combined with 5-FU on the invasion and metastasis of advanced metastatic or primary colorectal cancer in hypoxic environment. The cytotoxicity of quercetin or/and 5-FU on colon cancer cells using CCK8 assay, Hoechst 33342, flow cytometry and AO staining. The effects of quercetin or/and 5-FU on the migration and invasion were determined by transwell, cell scratching method and murine xenograft models. The potential mechanism was explored by Western blot and immunofluorescent assay. The results revealed quercetin effectively inhibited the invasion and migration of high metastatic advanced colon cancer LOVO cells under hypoxia through the inhibition of ROS and the expression of HIF-1α and PI3K/AKT pathway. Combination of quercetin and 5-FU could promote the inhibition of 5-FU on the invasion and migration of LOVO cells. Moreover, quercetin also significantly inhibited the proliferation of either LOVO cells or HT-29 ​cells under hypoxia by inducing apoptosis and autophagy, particularly, showing stronger inhibition on HT-29 ​cells than LOVO cells. In conclusion, quercetin inhibited the invasion and migration of advanced metastatic colon cancer LOVO cells under hypoxia through inhibition of ROS and HIF-1α expression and the downregulation of PI3K/AKT pathway. Moreover, quercetin alone or in combination with 5-FU can effectively inhibit the invasion and migration of high metastatic advanced colon cancer. Quercetin has the potential to be used as an effective anti-colon cancer drug alone or in combination for the clinical treatment of advanced colon cancer.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Natural product databases for drug discovery: Features and applications” [Pharmaceut. Sci. Adv. 2 (2024) 100050]","authors":"Tao Zeng,&nbsp;Jiahao Li,&nbsp;Ruibo Wu","doi":"10.1016/j.pscia.2024.100054","DOIUrl":"10.1016/j.pscia.2024.100054","url":null,"abstract":"","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and characterization of micellar nanoparticles using crude saponins from five Congolese plant species","authors":"Pathy B. Lokole ,&nbsp;Nadège K. Ngombe ,&nbsp;Dave I. Motomba ,&nbsp;Justin B. Safari ,&nbsp;Michel K. Mpuza ,&nbsp;Rui W.M. Krause ,&nbsp;Paulin K. Mutwale ,&nbsp;Christian I. Nkanga","doi":"10.1016/j.pscia.2024.100055","DOIUrl":"10.1016/j.pscia.2024.100055","url":null,"abstract":"<div><div>Nanoparticles (NPs) have significantly advanced medical applications, including drug delivery, immunotherapy, vaccines, and diagnostics. This versatility is partly due to the potential of tailoring NPs from multiple sources. Notably, saponins, amphiphilic plant metabolites, have shown great promise in NP formulation. This study explored the development of micellar NPs using saponin crude fractions (SCFs) extracted from five Congolese plant species: <em>Millettia laurentii, Penthaclethra eetveldeana</em>, <em>Schwenckia americana</em>, <em>Musa paradisiaca,</em> and <em>Musa sapientum</em>. Plant materials were subjected to histological examination through optical microscopy, while phytochemical analyses by thin-layer chromatography confirmed the presence and predominance of saponins in the SCFs. We used a phthalocyanine-isoniazid hybrid (<em>Pc</em>-INH) as a hydrophobic probe to determine the critical micellar concentrations of SCFs and explore the feasibility of developing cost-effective saponin-based micelles (SBMs). Phytochemical screenings indicated saponins in the extracted SCF and other metabolites like flavonoids, phenolic acids, and anthocyanins. Dynamic light scattering and transmission electron microscopy analyses revealed the formation of nano-sized particles, particularly noting SBMs from <em>P. eetveldeana</em> with notable dimensions (157 ​nm, PDI of 0.27, and ZP of −4.01 ​mV) and spherical shape. The micelles from <em>M. laurentii</em> exhibited superior encapsulation efficiency for <em>Pc</em>-INH (55%) compared to control micelles formulated from pure saponin (33%). <em>In vitro</em> tests showed that <em>M. paradisiaca</em> SBMs have the best safety profile for red blood cells, with a 10% hemolysis rate compared to a 150% rate for bulk SCFs. However, there is a significant difference between SCFs and SBMs (<em>p</em> ​&lt; ​0.0001). The release profiles of <em>M. paradisiaca</em> SBMs show a pH-dependent relationship, suggesting potential for stimuli-responsive drug delivery. This work lays the foundation for leveraging plant-derived crude saponins in nanotechnology, emphazising their encapsulation efficiency, controlled release potential, and biocompatibility, paving the way for the cost-effective production of high-value biomedical NPs.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sos1 deficiency ameliorates oncogenic KRAS-mediated hematopoietic stem cell exhaustion and myeloid progenitor expansion","authors":"Maoshuo Yang ,&nbsp;Lanlan Liu ,&nbsp;Yaqing Miao ,&nbsp;Yongxin Jia ,&nbsp;Sijia Tian ,&nbsp;Limei Wang ,&nbsp;Fabao Liu ,&nbsp;Xiaona You","doi":"10.1016/j.pscia.2024.100053","DOIUrl":"10.1016/j.pscia.2024.100053","url":null,"abstract":"<div><div>Constitutive <em>KRAS</em> activating mutations are prevalent in hematopoietic malignancies. Our previous study showed that the deficiency of <em>Sos1</em> prolongs the survival of <em>Kras</em>^G12D/+ mice. However, whether <em>Sos1</em> deletion ameliorates oncogenic <em>Kras</em>-mediated hematopoietic defects remains unknown. Here, we found that <em>Sos1</em> deletion restored <em>Kras</em>^G12D-mediated hematopoietic stem cell (HSC) and multipotent progenitor (MPP) exhaustion by maintaining quiescent HSC and MPP pools. <em>Sos1</em> knockout attenuates hyperactivation of ERK signaling in <em>Kras</em>^G12D/+ HSCs and MPPs. Additionally, the loss of <em>Sos1</em> reduced the frequency and colony-forming capability of myeloid progenitors in <em>Kras</em>^G12D/+ mice, resulting in a less severe myeloproliferative neoplasm phenotype. Moreover, <em>Sos1</em> knockout prolonged the survival of <em>Kras</em>^G12D/+ mice in a cell-autonomous manner. In general, cells with <em>Sos1</em> deletion remained sensitive to MEK and JAK inhibition, suggesting that combined Sos1 inhibition and other therapies could be a promising strategy for the treatment of oncogenic <em>KRAS</em>-driven leukemia.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"2 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}