ABSTRACT
In April 2023, we successfully treated a 21-year-old patient afflicted with a rare giant cystadenocarcinoma, an extraordinarily large mucinous ovarian tumor that weighed nearly 25 kg. The preoperative dimensions of the tumor measured 40 × 30 × 34 cm, with the tumor's weight nearing 25 kg. Despite its uncommon nature, we elected to perform a right adnexectomy, greater omentectomy, and peritoneal biopsy during the surgical intervention due to the patient's youth and the family's expressed desire to preserve fertility. In the subsequent August follow-up, CT scans revealed the complete resolution of the tumor, accompanied by the normalization of tumor markers, indicating a favorable outcome.
ABSTRACT
Epithelial ovarian cancer (EOC) is a fatal gynecological malignancy with limited therapeutic options. Previous research has demonstrated that Tripterygium glycosides (GTW) can enhance effectiveness of cisplatin (DDP) chemotherapy against EOC. However, the underlying mechanism of GTW alleviating EOC still remains unclear. In this article, an ID8 cell-derived xenograft mouse model was established to evaluate the anti-tumor efficacy of GTW combined with DDP. Consistent with previous findings, the results suggested that GTW combined with DDP can exhibit a stronger tumor suppressive effect than DDP alone. Additionally, GTW was found can further exert gastrointestinal protection against DDP by reducing pathological damage on colon tissue. Secondly, to verify whether gut microbiota play an instrumental role in GTW's anticancer effect, we treated mice models with antibiotic to eliminate gut microbiota. And our experimental results indicated that all drug groups showed a weaker tumor suppressive effect and more severe gastrointestinal damage post antibiotic supplement. At genus level, the relative abundance of Lactobacillus was dramatically diminished by the antibiotic treatment, while combined treatment of GTW and DDP can significantly restore the level. Moreover, we performed Lactobacillus acidophilus transplantation and healthy mice fecal microbiota transplantation experiments to further investigate the link between the anticancer effect of GTW and gut microbiota. Our results suggested that both cisplatin-sensitizing and intestinal barrier-protecting effects of GTW can be recovered to a different extent. In conclusion, our results indicated that GTW is a promising chemosensitization and intestinal barrier repair drug for EOC, and the potential mechanism may corelate with the restoration of the compromised intestinal microbial balance.
Subject(s)
Gastrointestinal Microbiome , Ovarian Neoplasms , Humans , Mice , Female , Animals , Cisplatin/pharmacology , Cisplatin/therapeutic use , Tripterygium , Glycosides/pharmacology , Glycosides/therapeutic use , Carcinoma, Ovarian Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic useABSTRACT
Based on actual atmospheric observations of internal mixing of light-absorbing brown carbon (BrC)-coated black carbon (BC), the optical properties of mixed black and brown carbon aerosols (BBC) were calculated using four mixing models (external mixing, core-shell, Bruggeman, and Maxwell-Garnett models), and changes in their optical properties with wavelength were compared and analyzed. Under the assumption of different volumetric mixing ratios (VR=VBC/VBBC), there is little difference in volumetric absorptive coefficient (Kab) of BBC in these models in the ultraviolet band where both BC and BrC have strong absorption, particularly in the ultraviolet A band. In visible and near-infrared bands, the three internal mixing models significantly reduce the single scattering albedo compared to the external mixing scenario. In addition, the widely used core-shell model was used to evaluate the effects of BrC shell thickness and environmental relative humidity (RH) on the optical properties of BBC. The impacts of these factors are mainly seen in ultraviolet and visible bands. The volumetric extinction coefficient (Kex) decreases with BrC shell thickness under a fixed BC core radius (0.12 µm) in these bands. This is because the radiation reaching the surface of BC particles is reduced under the absorption of less efficient BrC shells (known as the blocking effect), which is different from the BC and light-scattering aerosols internal mixing scenario. Moreover, the Kex and Kab of BBC decrease with RH, which is mainly due to both the increasing thickness of the BrC shell and the change in the complex refractive index of the BrC shell. Based on the assumptions of unchanged BC core parameters and actual observations, the extinction ability increases when BrC particles are more light-scattering in the ultraviolet and visible bands. The increase in extinction is mainly from scattering, rather than absorption. However, the situation is the opposite in the near-infrared band.
ABSTRACT
Large variations in the growth of atmospheric methane, a prominent greenhouse gas, are driven by a diverse range of anthropogenic and natural emissions and by loss from oxidation by the hydroxyl radical. We used a decade-long dataset (2010-2019) of satellite observations of methane to show that tropical terrestrial emissions explain more than 80% of the observed changes in the global atmospheric methane growth rate over this period. Using correlative meteorological analyses, we show strong seasonal correlations (r = 0.6-0.8) between large-scale changes in sea surface temperature over the tropical oceans and regional variations in methane emissions (via changes in rainfall and temperature) over tropical South America and tropical Africa. Existing predictive skill for sea surface temperature variations could therefore be used to help forecast variations in global atmospheric methane.
Subject(s)
Greenhouse Gases , Methane , Africa , Greenhouse Gases/analysis , Hydroxyl Radical , Methane/analysis , Oceans and SeasABSTRACT
BACKGROUND Ferulic acid is an antioxidant phenolic compound derived from plants, which has effects on cancer cells. This study aimed to investigate the effects of ferulic acid on HeLa and Caski human cervical carcinoma cells and the molecular mechanisms involved. MATERIAL AND METHODS HeLa and Caski human cervical carcinoma cells were grown in culture and treated with increasing doses of ferulic acid. The MTT assay was used to evaluate cell viability. Flow cytometry was performed with 4',6-diamidino-2-phenylindole (DAPI) and Annexin V staining for cell apoptosis. The expression of myeloid leukemia cell differentiation-1 (Mcl-1) protein and MCL-1 mRNA were determined by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS Ferulic acid significantly reduced HeLa and Caski cell viability in the concentration range of 4-20 µM (P<0.05). Ferulic acid treatment promoted DNA condensation and significantly increased apoptosis in Caski cells (P<0.05). Ferulic acid treatment resulted in the activation of pro-caspase-3, pro-caspase-8, pro-caspase-9, and PARP. The MTT assay showed that ferulic acid did not reduce the viability of Caski cells treated with the caspase inhibitor, z-VAD-fmk. Ferulic acid reduced the levels of Bcl-2 and Mcl-1, and increased the levels of Bax and reactive oxygen species (ROS). In Caski cells, Akt and PI3K phosphorylation were reduced by ferulic acid in a concentration-dependent manner. CONCLUSIONS The effects of ferulic acid were dose-dependent and resulted in cell cytotoxicity and apoptosis of HeLa and Caski cells, and the PI3K/Akt signaling pathway was down-regulated in Caski cells.
Subject(s)
Apoptosis/drug effects , Coumaric Acids/pharmacology , Down-Regulation , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Uterine Cervical Neoplasms/pathology , Caspases/metabolism , DNA Damage , Down-Regulation/drug effects , Enzyme Activation/drug effects , Female , HeLa Cells , Humans , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effectsABSTRACT
This study was designed to investigate the antitumor activity of triptolide in ovarian cancer inoculated with SKOV3 and SKOV3/cisplatin (DDP) cells, and to assess the mechanisms. In-vivo and in-vitro experiments were designed to evaluate the effects of triptolide on the tumor growth of SKOV3 and SKOV3/DDP cells. The experiments were divided into four groups: a SKOV3 group, a SKOV3 + TP treatment group, a SKOV3/DDP group and a SKOV3/DDP + TP treatment group. The expression of Sorcin, vascular endothelial growth factor and matrix metalloproteinase-2 were detected by western blotting and immunohistochemistry. Tumor cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. In-vitro experiments showed that compared with SKOV3 control group, the level of colony-stimulating factor 1 and expression of Sorcin in SKOV3/DDP was significantly higher. Interestingly, triptolide treatment could reduce colony-stimulating factor 1 level and expression of Sorcin in both SKOV3 and SKOV3/DDP cell lines. In-vivo experiments showed that tissue necrosis area in SKOV3 + TP and SKOV3/DDP + TP was larger than SKOV3 and SKOV3/DDP group, respectively. Triptolide treatment induced apoptosis in both SKOV3 and SKOV3/DDP cells. Compared with SKOV3 group, the size of tumors was large, and the expression of MMP-2, Sorcin and vascular endothelial growth factor was higher in SKOV3/DDP group. Triptolide treatment reduced the size of tumors, and the expression of MMP-2, Sorcin and vascular endothelial growth factor in SKOV3/DDP as well as in SKOV3 tumors. In conclusion, triptolide has antitumor activity in both SKOV3 and SKOV3/DDP cells likely through inducing apoptosis and regulating MMP-2, Sorcin and vascular endothelial growth factor expression.
Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Biomarkers, Tumor/metabolism , Diterpenes/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Ovarian Neoplasms/pathology , Phenanthrenes/pharmacology , Animals , Apoptosis , Biomarkers, Tumor/genetics , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Cell Proliferation , Epoxy Compounds/pharmacology , Female , Humans , In Vitro Techniques , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Xenograft Model Antitumor AssaysABSTRACT
Recurrent liver cancer after surgery is often treated with radiotherapy, which induces liver damage. It has been documented that activation of the TGF-ß and NF-κB signaling pathways plays important roles in irradiation-induced liver pathologies. However, the significance of mTOR signaling remains undefined after irradiation exposure. In the present study, we investigated the effects of inhibiting mTORC1 signaling on irradiated livers. Male C57BL/6J mice were acutely exposed to 8.0 Gy of X-ray total body irradiation and subsequently treated with rapamycin. The effects of rapamycin treatment on irradiated livers were examined at days 1, 3, and 7 after exposure. The results showed that 8.0 Gy of irradiation resulted in hepatocyte edema, hemorrhage, and sinusoidal congestion along with a decrease of ALB expression. Exposure of mice to irradiation significantly activated the mTORC1 signaling pathway determined by pS6 and p-mTOR expression via western blot and immunostaining. Transient inhibition of mTORC1 signaling by rapamycin treatment consistently accelerated liver recovery from irradiation, which was evidenced by decreasing sinusoidal congestion and increasing ALB expression after irradiation. The protective role of rapamycin on irradiated livers might be mediated by decreasing cellular apoptosis and increasing autophagy. These data suggest that transient inhibition of mTORC1 signaling by rapamycin protects livers against irradiation-induced damage.
ABSTRACT
Introduction: Advanced ovarian cancer is the main cause of ovarian cancer deaths, and it is important to seek safe and effective phytochemicals to suppress cancer or lower the chemotherapy resistance of ovarian cancer. Methods: This study evaluated the effect of Triptolide (TPL) on the proliferation, cycle distribution, apoptosis, and ultra-structure of COC1/DDP cells in vitro, as well as the anti-cancer effect and sensibilisation effect of TPL in vivo. Results: The results indicated that TPL could significantly inhibit the growth of COC1/DDP cells (P<0.05), and 3 ng/ml TPL and 50 ng/ml TPL made COC1/DDP cells present obvious apoptosis characteristics and arrest 35% and 55% of COC/DDP cells in the G0/G1 phase, respectively (P<0.05). The animal experiments also indicated that 0.1mg/kg.d TPL significantly reduced the tumour weight and the spleen cell transformation rate (SI), and it lowered the inflammatory factors IL-2 and TNF-a in rat serum (P<0.05). Moreover, the significant reduction of p-Akt and p-GSK3ß made the TPL+DDP possess the highest apoptosis rate [(51.13±3.325)%] in COC1/DDP cells. Conclusions: TPL used in combination with DDP may produce a synergistic anti-cancer effect that warrants further investigation for its potential clinical applications in the treatment of epithelial ovarian cancer.