Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains unclear. Methods We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAP-periodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM specimens.Glioma stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional culture.For the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were studied. Results VM and high pATM expression occurred in 38.5%and 41.8%of tumors,respectively,and were significantly associated with reduced progression-free and overall survival.Patients with VM-positive GBMs exhibited higher pATM levels(rs=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in vitro.ATM inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin B2. Conclusion VM may predict a poor GBM prognosis and is associated with pATM expression.We propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.

Objective To investigate whether norepinephrine (NE) regulates the oxidative stress in human endom-etrial epithelial cells (hEECs) by activating nuclear factor E2-related factor 2(Nrf2)/ heme oxygenase -1(HO-1) signal pathway.Methods Cultured hEECs were used.The expression of α and β adrenergic receptors was detec-ted by reverse transcription-polymerase chain reaction (RT-PCR).Cell counting kit-8(CCK-8) assay was applied to test the effect of NE on cell viability, then the cells were divided into Control group and NE treatment group, and the appropriate concentrations were chosen.The expression of tight junction proteins Occludin and zona occludens-1(ZO-1), apoptosis-related proteins apoptosis-related protein B-cell lymphoma-2 protein(Bcl-2) and Bcl-2 associ-ated X protein(Bax) , antioxidant proteins Nrf2 and HO-1 were examined by Western blot.The apoptosis was de-tected by flow cytometry.The malonaldehyde (MDA) and superoxide dismutase(SOD) in the cell culture medium were detected by enzyme-linked immunosorbent assays kit (ELISA).Results The mRNA expression of α1 a,α1 b,α2 a,α2 b,α2 c,β1, β3 was detected in the hEECs.After the NE treatment, no significant change in cell viability was observed in low concentration (5 μmol/L and 10 μmol/L) groups, while 15 μmol/L and 20μmol/L NE treatments for 6 h or 24 h promoted the cell viability significantly.The expression of ZO-1 and Occlu-din increased significantly in 15 μmol/L group after 24 h treatment, the expression of ZO-1 decreased in 6 h treat-ment group, significant down regulation was observed after 15 μmol/L NE application, the expression of Occludin increased in 6 h group.The cell apoptosis increased compared with the control group after NE stimulation, espe-cially a significantly increase in 6 h 15 μmol/L group was detected,while the fall in increased apoptosis was ob-served after 24 h treatment.The ration of Bcl-2/Bax>1.The expression of Nrf2 and HO-1 was elevated by NE.There was no obvious change in MDA level while significant elevation in SOD was detected in cell culture medium.Conclusion Nrf2/HO-1 signal is activated after application of NE to the hEECs, which may responsible for the upregulation of SOD, antioxidant and anti-apoptotic effect in the hEECs.

Cervical cancer, the most common gynecological malignancy, significantly and adversely affects women's physical health and well-being. Traditional surgical interventions and chemotherapy, while potentially effective, often entail serious side effects that have led to an urgent need for novel therapeutic methods. Photothermal therapy (PTT) has emerged as a promising approach due to its ability to minimize damage to healthy tissue. Connecting a biothiol detection group to PTT-sensitive molecules can improve tumor targeting and further minimize potential side effects. In this study, we developed a near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-mode probe, S-NBD, which demonstrated robust PTT performance. This innovative probe is capable of activating NIRF/PA signals to enable the detection of biothiols with high emission wavelength (838 nm) and large Stokes shift (178 nm), allowing for in vivo monitoring of cancer cells. Additionally, the probe achieved an outstanding photothermal conversion efficiency of 67.1%. The application of laser irradiation (660 nm, 1.0 W/cm², 5 min) was able to achieve complete tumor ablation without recurrence. In summary, this seminal study presents a pioneering NIRF/PA dual-mode dicyanoisophorone-based probe for biothiol imaging, incorporating features from PTT for the first time. This pioneering approach achieves the dual objectives of improving tumor diagnosis and treatment.

Based on the traditional Chinese medicine （TCM） theories of holism， syndrome differentiation and treatment， and preventive treatment of disease， the concept of whole course management of tumors throughout the treatment process is advocated. The strategy includes preventive treatment before tumor therapy， focusing on protecting the body's vital qi and strengthening the spleen and Qi. TCM formulas such as Sijunzi Decoction （四君子汤）， Shenling Baizhu San （参苓白术散） and Xiangsha Liujunzi Decoction（香砂六君子汤） are used to enhance platelet reserves. The main therapeutic methods during tumor conventional therapy include preventing disease transformation and strengthening vital qi to eliminate pathogenic factor， by invigorating spleen and soothing liver， nourishing liver and kidney， purging fire for removing toxin， and removing blood stasis for promoting tissue regeneration. TCM formulas such as Xiangsha Liujunzi Decoction （香砂六君子汤）， Shenling Baizhu Powder （参苓白术散）， Fuzi Lizhong Decoction （附子理中汤）， Zhibai Dihuang Decoction （知柏地黄汤）， and Qiangen Powder （茜根散）are used to reduce platelet destruction and depletion during tumor therapy and reverse the worsening trend. After tumor conventional therapy， the focus is on preventing relapse， adjusting the balance of Yin and Yang， by nourishing the kidneys， spleen， and lungs. TCM formulas such as Dingkun Pill （定坤丹）and Zuogui Pill （左归丸） are used with modifications to prevent thrombocytopenia. The staged prevention and treatment of tumor treatment-induced thrombocytopenia using TCM can maximize the benefits for patients.

Humans ; Computed Tomography Angiography ; Deep Learning ; Coronary Angiography ; Coronary Artery Disease ; Tomography, X-Ray Computed ; Coronary Stenosis/diagnosis* ; Retrospective Studies ; Fractional Flow Reserve, Myocardial ; Predictive Value of Tests

Objective: To investigate the effects of cathepsin S(Cat S) on proliferation, migration and invasion of osteosarcoma cells and its potential regulatory mechanism. Methods: Normal osteoblasts(hFOB) and osteosarcoma cells(SAOS2 and MG63) were selected as the subjects of this study.Cat S small interfering(si) RNA(si-Cat S) and negative control sequence(si-NC) were transfected into SAOS2 and MG63 cells to modulate the expression of Cat S in osteosarcoma cells.The experimental cells were randomly divided into four groups: hFOB group(hFOB cells),Control group(untransfected SAOS2 or MG63 cells),si-NC group(SAOS2 or MG63 cells transfected with si-NC) and si-Cat S group(SAOS2 or MG63 cells transfected with si-Cat S).The expression of Cat S in SAOS2 and MG63 cells was detected by RT-PCR and Western blot.Effect of Cat S knockdown on the proliferation of SAOS2 and MG63 cells was assessed by CCK-8 and clone formation assays.And effects of Cat S knockdown on the migration and invasion of SAOS2 and MG63 cells were determined by wound-healing and Transwell assays, respectively.Western blot assay was performed to measure the effects of SAOS2 knockdown on the expressions of apoptosis-related proteins(Bcl-2,Bax and Caspase-3) and Wnt/β-catenin pathway related proteins(LRP5,β-catenin, C-myc and Cyclin D1) in SAOS2 cells. Results: Compared with hFOB group, the expression of Cat S in SAOS2 group and MG63 group was upregulated(P<0.001).In addition, compared with si-NC group, the proliferation, migration and invasion of cells in si-Cat S group were reduced(P<0. 001). Results of Western blot showed that compared with si-NC group,the expression of Bcl-2 in si-Cat S group was downregulated,while the expression of Bax and Caspase-3 were upregulated(P<0. 001). Meanwhile,compared with si-NC group,the expression of LRP5,β-catenin,C-myc and Cyclin D1 in si-Cat S group was downregulated(P<0. 001). Conclusion Cat S siRNA knockdown can inhibit the proliferation,migration and invasion of osteosarcoma cells and induce apoptosis by regulating Wnt/β-catenin pathway,indicating that Cat S may be one of the potential targets for the treatment of osteosarcoma.

BACKGROUND: It has been recognized that the traditional herbal treatment and daoyin exercises(physical and breathing exercise) can relieve the symptoms such as tiredness of cancer patients and strengthen the tolerance to chemical drugs. But the criterion of quantitative evaluation for the effect should be scientific.OBJECTIVE: To evaluate the influence of Chinese herb for strengthening the body resistance and daoyin exercises on the survival state of lung cancer patients with the evaluation scale of life quality.DESIGN: Non-randomized and concurrent controlled trial.SETTING: Department of Integrated Traditional Chinese and Western Medicine, Clinical Cancer Research Center, Guangzhou Medical College;Zhaoqing First People's Hospital.PARTICIPANTS: Totally 60 inpatients of the Department of Integrated Traditional Chinese and Western Medicine of Clinical Cancer Research Center of Guangzhou Medical College were enrolled from October 1997 to March 2001 in the study. All of them were volunteers. There were 41 males and 19 females, 30 patients in the treatment group and 30 in the control group.METHODS: The treatment group was given chemical therapy, at the same time, the herbal treatment and daoyin exercises. The control group was given chemical therapy only. The same chemical therapy was applied to both groups. The appointed doctor familiar with the evaluation table of quality of life was responsible for evaluating the quality of life of the patients in the two groups before and after treatment and the observation of their accomplishment of chemical therapy. The evaluation table of quality of life of Chinese lung cancer patients was used in the evaluation. The table included 5 factors: the physiological state caused by lung cancer, social/family state, relation of altitude towards doctor and disease, emotional state, and functional state. The statistical analysis was done to see the accomplishment of chemical therapy of two groups.chemical therapy of the two groups.RESULTS: According to the intention-to-treat analysis, 60 patients all completed the whole process of study. The comparison of the score before physiological state after treatment was obviously lower than that before treatment[ (14. 1 ± 3.2), (31.7 ±2.9) scores, P ＜ 0.01] and of control state was obviously higher than that before treatment[(25.2±3.1),(12.2 ±2.3)scores, P ＜0.01] and of control group[(19.1 ±2.2) scores,after treatment was obviously higher than that before treatment[ (37.4 ± 5.2),(24.2 ±3.5) scores, P ＜0. 01 ]and of control group[ (29. 1 ±3.4)scores, P before treatment[ (43.8 ± 5.6), (28.5 ± 4. 7) scores, P ＜ 0. 01 ] and of tional state after treatment was obviously higher than that of before treatment [(26.3±2.3), (17.3±3.3) scores, P ＜ 0.01] and of control group [ (20. 3 ± 1.1) scores, P ＜ 0. 05] . The accomplishment rate of chemical control group, 26 patients accomplished 1 course(87%, 26/30) and 18rate of 2 courses of chemical therapy of treatment group was obviously higher than that of control group ( P ＜ 0.05 ).CONCLUSION: The herbal treatment combined with daoyin exercises can improve the tolerance of lung cancer patients for chemical therapy and relieve the symptoms, thus improving their quality of life.

OBJECTIVETo study the effect of chemotherapy assisted with shenqi fuzheng injection (SFI) on senile patients with non-small cell lung cancer (NSCLC).

METHODSOne hundred and twenty old patients with NSCLC were treated with NP chemotherapeutic protocol, to the 60 patients in the treated group among them, additional medication of SFI was started one week before the beginning of chemotherapy. The short-term therapeutic efficacy, long-term survival rate, changes on quality of life (QOL) and immune function of patients, and hematological toxicity of therapy were observed.

RESULTSDifference between the two groups on short-term therapeutic effect, 1- and 2-year survival rate showed no significance (P>0.05), but the 3-year survival rate in the treated group was 26.6%, while that in the control group was 11.7%, showed that the former was higher than the latter. After treatment QOL of the treated group was better than that of the control (P<0.05). Besides, the hematological toxicity and affection on immune function of chemotherapy after treatment in the treated group were all lower than those in the control group showing significant difference (P<0.05).

CONCLUSIONSFI has definite toxicity relieving effect on chemotherapy in treating senile NSCLC.

Adenocarcinoma ; drug therapy ; immunology ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; immunology ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Injections ; Lung Neoplasms ; drug therapy ; immunology ; Male ; Middle Aged ; Phytotherapy ; Quality of Life