-
Integrative Cancer Therapies 2024(SM) is a commonly used herb in traditional Chinese medicine (TCM) and has been used in the treatment of pancreatic cancer to relieve the symptom of "blood stasis and...
CONTEXT
(SM) is a commonly used herb in traditional Chinese medicine (TCM) and has been used in the treatment of pancreatic cancer to relieve the symptom of "blood stasis and toxin accumulation." Tanshinones (Tan), the main lipophilic constituents extracted from the roots and rhizomes of SM, have been reported to possess anticancer functions in several cancers. But the mechanism of how the active components work in pancreatic cancer still need to be clarified.
OBJECTIVE
In this study, we aimed to investigate the therapeutic potential of Tan in pancreatic cancer and elucidate the underlying mechanisms.
MATERIALS AND METHODS
The viabilities of PANC-1 and Bxpc-3 cells were determined by MTT assay, after treatment with various concentrations of Tan. The apoptotic cells were quantified by annexin V-FITC/PI staining and DAPI staining assays. The expression of relative proteins was used western blotting. Tumor growth was assessed by subcutaneously inoculating cells into C57BL/6 mice.
RESULTS
Our experiments discovered that Tan effectively suppressed pancreatic cancer cell proliferation and promoted apoptosis. Mechanistically, we propose that Tan enhances intracellular ROS levels by activating the AKT/FOXO3/SOD2 signaling pathway, ultimately leading to apoptosis in pancreatic cancer cells. In vivo assay showed the antitumor effect of Tan.
CONCLUSION
Tan, a natural compound from , was found to effectively suppress pancreatic cancer cell proliferation and promote apoptosis both in vitro and in vivo. Mechanistically, we propose a positive feedback loop mechanism. These findings provide valuable insights into the molecular pathways driving pancreatic cancer progression.
Topics: Pancreatic Neoplasms; Salvia miltiorrhiza; Abietanes; Apoptosis; Animals; Humans; Forkhead Box Protein O3; Mice; Proto-Oncogene Proteins c-akt; Signal Transduction; Cell Line, Tumor; Reactive Oxygen Species; Plant Extracts; Mice, Inbred C57BL; Cell Proliferation
PubMed: 38899834
DOI: 10.1177/15347354241258961 -
Cancer Medicine Jun 2024There has been significant progress made in developing novel targeted therapies in the neoadjuvant setting for non-metastatic HER2-positive breast cancer, which may be...
AIM
There has been significant progress made in developing novel targeted therapies in the neoadjuvant setting for non-metastatic HER2-positive breast cancer, which may be used in combination with conventional chemotherapy to optimise pathological responses at surgery. However, these therapies, particularly the chemotherapeutic components, may portend significant and long-lasting toxicity. Hence, de-escalation of treatment intensity has been an area of interest and was evaluated in the phase II NeoSphere study. Herein, we report the real-world pathological and survival outcomes from neoadjuvant taxane and dual HER2 blockade recorded at our centre.
METHODS
This was a retrospective cohort study of patients receiving neoadjuvant pertuzumab, trastuzumab and taxane chemotherapy for non-metastatic HER2-positive breast cancer at a single centre in Sydney, Australia. We collected data pertaining to baseline demographic characteristics, pathological response rates, post-surgical prescribing patterns and also undertook survival analyses for invasive disease-free survival (iDFS) as well as exploratory analyses for correlations between pre-specified clinicopathologic factors and pathological response at surgery.
RESULTS
Our population was largely similar at baseline to the NeoSphere study. 71 patients were included in the final analysis. 61% achieved a pathological complete response (pCR). Three patients received conventional chemotherapy in the adjuvant setting. 92% of included patients were alive and disease-free at 3 years of follow-up. Only 3 events of recurrence or death were recorded at a median follow-up of 32 months. No significant difference in iDFS was noted between patients achieving pCR and those with residual disease at surgery.
CONCLUSION
This study demonstrates that de-escalated adjuvant treatment for HER2-positive early breast cancer achieved favourable pathological and long-term outcomes comparable to large trials, some utilising more intensive chemotherapeutic components.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; Middle Aged; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies; Adult; Aged; Australia; Neoplasm Staging; Treatment Outcome; Trastuzumab; Taxoids; Bridged-Ring Compounds; Antibodies, Monoclonal, Humanized; Chemotherapy, Adjuvant
PubMed: 38899493
DOI: 10.1002/cam4.7325 -
BMC Plant Biology Jun 2024Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and...
Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and underlying mechanisms during the elongation and growth process of asparagus stems, we documented the growth pattern of asparagus and selected stem segments from four consecutive elongation stages using physiological and transcriptome analyses. Notably, the growth rate of asparagus accelerated at a length of 25 cm. A significant decrease in the concentration of sucrose, fructose, glucose, and additional sugars was observed in the elongation region of tender stems. Conversely, the levels of auxin and gibberellins(GAs) were elevated along with increased activity of enzymes involved in sucrose degradation. A significant positive correlation existed between auxin, GAs, and enzymes involved in sucrose degradation. The ABA content gradually increased with stem elongation. The tissue section showed that cell elongation is an inherent manifestation of stem elongation. The differential genes screened by transcriptome analysis were enriched in pathways such as starch and sucrose metabolism, phytohormone synthesis metabolism, and signal transduction. The expression levels of genes such as ARF, GA20ox, NCED, PIF4, and otherswere upregulated during stem elongation, while DAO, GA2ox, and other genes were downregulated. The gene expression level was consistent with changes in hormone content and influenced the cell length elongation. Additionally, the expression results of RT-qPCR were consistent with RNA-seq. The observed variations in gene expression levels, endogenous hormones and sugar changes during the elongation and growth of asparagus tender stems offer valuable insights for future investigations into the molecular mechanisms of asparagus stem growth and development and provide a theoretical foundation for cultivation and production practices.
Topics: Asparagus Plant; Plant Stems; Plant Growth Regulators; Gene Expression Profiling; Gene Expression Regulation, Plant; Transcriptome; Sugars; Gibberellins
PubMed: 38898382
DOI: 10.1186/s12870-024-05277-0 -
BMJ (Clinical Research Ed.) Jun 2024To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.
OBJECTIVE
To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma.
DESIGN
Phase 3, open label, multicentre, randomised trial.
SETTING
Four hospitals located in China between September 2019 and August 2022.
PARTICIPANTS
Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma.
INTERVENTIONS
Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m on day 1), cisplatin (60 mg/m on day 1), and capecitabine (1000 mg/m twice on days 1-14) or gemcitabine (1 g/m on days 1 and 8) and cisplatin (80 mg/m on day 1).
MAIN OUTCOME MEASURES
Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population.
RESULTS
The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) 13/40 (33%); P=0.02), neutropenia (6/41 (15%) 16/40 (40%); P=0.01), and anaemia (1/41 (2%) 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up.
CONCLUSION
The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR1900027112.
Topics: Humans; Cisplatin; Male; Middle Aged; Female; Gemcitabine; Nasopharyngeal Carcinoma; Deoxycytidine; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Adult; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Paclitaxel; Albumins; Aged; Progression-Free Survival; China; Neoplasm Metastasis
PubMed: 38897625
DOI: 10.1136/bmj-2023-077890 -
Journal of Materials Science. Materials... Jun 2024This study leverages nanotechnology by encapsulating indocyanine green (ICG) and paclitaxel (Tax) using zeolitic imidazolate frameworks-8 (ZIF-8) as a scaffold. This...
This study leverages nanotechnology by encapsulating indocyanine green (ICG) and paclitaxel (Tax) using zeolitic imidazolate frameworks-8 (ZIF-8) as a scaffold. This study aims to investigate the chemo-photothermal therapeutic potential of ZIF-8@ICG@Tax nanoparticles (NPs) in the treatment of non-small cell lung cancer (NSCLC). An "all-in-one" theranostic ZIF-8@ICG@Tax NPs was conducted by self-assembly based on electrostatic interaction. First, the photothermal effect, stability, pH responsiveness, drug release, and blood compatibility of ZIF-8@ICG@Tax were evaluated through in vitro testing. Furthermore, the hepatic and renal toxicity of ZIF-8@ICG@Tax were assessed through in vivo testing. Additionally, the anticancer effects of these nanoparticles were investigated both in vitro and in vivo. Uniform and stable chemo-photothermal ZIF-8@ICG@Tax NPs had been successfully synthesized and had outstanding drug releasing capacities. Moreover, ZIF-8@ICG@Tax NPs showed remarkable responsiveness dependent both on pH in the tumor microenvironment and NIR irradiation, allowing for targeted drug delivery and controlled drug release. NIR irradiation can enhance the tumor cell response to ZIF-8@ICG@Tax uptake, thereby promoting the anti-tumor growth in vitro and in vivo. ZIF-8@ICG@Tax and NIR irradiation have demonstrated remarkable synergistic anti-tumor growth properties compared to their individual components. This novel theranostic chemo-photothermal NPs hold great potential as a viable treatment option for NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Indocyanine Green; Humans; Animals; Lung Neoplasms; Hydrogen-Ion Concentration; Nanoparticles; Theranostic Nanomedicine; Paclitaxel; Drug Liberation; Mice; Zeolites; Infrared Rays; Phototherapy; Mice, Inbred BALB C; Cell Line, Tumor; A549 Cells; Metal-Organic Frameworks; Mice, Nude; Drug Delivery Systems; Imidazoles
PubMed: 38896160
DOI: 10.1007/s10856-024-06802-1 -
Molecules (Basel, Switzerland) Jun 2024Oridonin (Ori) is a naturally existing diterpenoid substance that mainly exists in the Chinese medicinal plant Rabdosia rubescens. It was previously found to possess...
Oridonin (Ori) is a naturally existing diterpenoid substance that mainly exists in the Chinese medicinal plant Rabdosia rubescens. It was previously found to possess intriguing biological properties; however, the quick clearance from plasma and limited solubility in water restricts its use as a drug. Several metal-organic frameworks (MOFs), having big surfaces and large pores, have recently been considered promising drug transporters. The zeolitic imidazolate framework-8 (ZIF-8), a form of MOF consisting of 2-methylimidazole with zinc ions, is structurally stable under physiologically neutral conditions, while it can degrade at low pH values such as in tumor cells. Herein, a nanosized drug delivery system, Ori@ZIF-8, was successfully designed for encapsulating and transporting oridonin to the tumor site. The drug loading of the prepared Ori@ZIF-8 was 26.78%, and the particles' mean size was 240.5 nm. In vitro, the release of Ori@ZIF-8 exhibited acid sensitivity, with a slow release under neutral conditions and rapid release of the drug under weakly acidic conditions. According to the in vitro anti-tumor experiments, Ori@ZIF-8 produced higher cytotoxicity than free Ori and induced apoptosis in A549 cancer cells. In conclusion, Ori@ZIF-8 could be a potential pH-responsive carrier to accurately release more oridonins at the tumor site.
Topics: Diterpenes, Kaurane; Metal-Organic Frameworks; Humans; Hydrogen-Ion Concentration; Drug Delivery Systems; Drug Liberation; Drug Carriers; A549 Cells; Cell Line, Tumor; Zeolites; Neoplasms; Antineoplastic Agents; Cell Survival; Imidazoles
PubMed: 38893518
DOI: 10.3390/molecules29112643 -
Molecules (Basel, Switzerland) Jun 2024To better assess the practical value and avoid potential risks of the traditionally medicinal and edible basidiomycete , which may arise from undescribed metabolites, a...
Combining the Elicitor Up-Regulated Production of Unusual Linear Diterpene-Derived Variants for an In-Depth Assessment of the Application Value and Risk of the Medicinal and Edible Basidiomycete .
To better assess the practical value and avoid potential risks of the traditionally medicinal and edible basidiomycete , which may arise from undescribed metabolites, a combination of elicitors was introduced for the first time to discover products from cryptic and low-expressed gene clusters under laboratory cultivation. Treating NJFU21 with the combination of five elicitors led to the upregulated production of a class of unusual linear diterpene-derived variants, including eleven new ones (-), along with three known ones (-). The structures and stereochemistry were determined by 1D and 2D NMR, HRESIMS, ECD, OR and VCD calculations. Notably, the elongation terminus of all the diterpenes was decorated by an unusual butenedioic acid moiety. Compound was a rare monocyclic diterpene, while - possessed a tetrahydrofuran moiety. The truncated metabolites , and belong to the trinorditerpenes. All the diterpenes displayed approximately 70% scavenging of hydroxyl radicals at 50 μM and null cytotoxic activity at 10 μM. In addition, compound exhibited potent antifungal activity against the plant pathogenic fungi , with MIC values of 8 μg/mL. Our findings indicated that this class of diterpenes could provide valuable protectants for cosmetic ingredients and the lead compounds for agricultural fungicide development.
Topics: Diterpenes; Schizophyllum; Molecular Structure; Up-Regulation; Humans
PubMed: 38893484
DOI: 10.3390/molecules29112608 -
Molecules (Basel, Switzerland) May 2024Baccatin III is a crucial precursor in the biosynthesis pathway of paclitaxel. Its main sources are extraction from or chemical synthesis using 10-deacetylbaccatin III...
Baccatin III is a crucial precursor in the biosynthesis pathway of paclitaxel. Its main sources are extraction from or chemical synthesis using 10-deacetylbaccatin III (10-DAB) as substrate. However, these preparation approaches exhibit serious limitations, including the low content of baccatin III in and the complicated steps of chemical synthesis. Heterologous expression of 10-deacetylbaccatin III-10-O-acetyltransferase (TcDBAT) in microbial strains for biotransformation of 10-DAB is a promising alternative strategy for baccatin III production. Here, the promotion effects of glycerol supply and slightly acidic conditions with a low-temperature on the catalysis of recombinant strain were clarified using 10-DAB as substrate. needles is renewable and the content of 10-DAB is relatively high, it can be used as an effective source of the catalytic substrate 10-DAB. Baccatin III was synthesized by integrating the extraction of 10-DAB from renewable needles and in situ whole-cell catalysis in this study. 40 g/L needles were converted into 20.66 mg/L baccatin III by optimizing and establishing a whole-cell catalytic bioprocess. The method used in this study can shorten the production process of extraction for baccatin III synthesis and provide a reliable strategy for the efficient production of baccatin III by recombinant strains and the improvement of resource utilization rate of needles.
Topics: Taxus; Biotransformation; Taxoids; Alkaloids; Plant Leaves; Acetyltransferases
PubMed: 38893462
DOI: 10.3390/molecules29112586 -
Molecules (Basel, Switzerland) May 2024Breast cancer is a major health concern and the leading cause of death among women worldwide. Standard treatment often involves surgery, radiotherapy, and chemotherapy,...
Breast cancer is a major health concern and the leading cause of death among women worldwide. Standard treatment often involves surgery, radiotherapy, and chemotherapy, but these come with side effects and limitations. Researchers are exploring natural compounds like baicalin and baicalein, derived from the plant, as potential complementary therapies. This study investigated the effects of baicalin and baicalein on the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel, commonly used chemotherapeutic drugs for breast cancer. The analysis included breast cancer cells (MCF-7) and human endothelial cells (HUVEC-ST), to assess potential effects on healthy tissues. We have found that baicalin and baicalein demonstrated cytotoxicity towards both cell lines, with more potent effects observed in baicalein. Both flavonoids, baicalin (167 µmol/L) and baicalein (95 µmol/L), synergistically enhanced the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel in breast cancer cells. In comparison, their effects on endothelial cells were mixed and depended on concentration and time. The results suggest that baicalin and baicalein might be promising complementary agents to improve the efficacy of doxorubicin and docetaxel anticancer activity. However, further research is needed to validate their safety and efficacy in clinical trials.
Topics: Humans; Flavonoids; Flavanones; Docetaxel; Doxorubicin; MCF-7 Cells; Apoptosis; Breast Neoplasms; Female; DNA Damage; Drug Synergism; Antineoplastic Agents; Cell Survival; Human Umbilical Vein Endothelial Cells
PubMed: 38893380
DOI: 10.3390/molecules29112503 -
Molecules (Basel, Switzerland) May 2024Kallopterolides A-I (-), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were...
Kallopterolides A-I (-), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were isolated from the Caribbean Sea plume . The structures and relative configurations of - were characterized by analysis of HR-MS, IR, UV, and NMR spectroscopic data in addition to computational methods and side-by-side comparisons with published NMR data of related congeners. An investigation was conducted as to the potential of the kallopterolides as plausible in vitro anti-inflammatory, antiprotozoal, and antituberculosis agents.
Topics: Diterpenes; Animals; Anthozoa; Antiprotozoal Agents; Caribbean Region; Molecular Structure; Anti-Inflammatory Agents; Magnetic Resonance Spectroscopy; Antitubercular Agents
PubMed: 38893370
DOI: 10.3390/molecules29112493