Synergistic Effect In Treatment Research Articles

Advancements in maize cultivation: synergistic effects of dry atmospheric plasma combined with plasma-activated water

Abstract In this study, we investigate the effects of pre-germinative and post-germinative plasma treatments, applied separately or in combination, to improve maize germination and early seedling development. Pre-germinative treatment consists of priming the seeds with a dry atmospheric plasma (DAP) generated by a dielectric barrier device, characterized by minimal radiative emission, low electrical power (4 W) and high emissions of O, OH and NO radicals. Post-germinative treatment, known as plasma-activated water (PAW), uses a single pin electrode device (SPED) to generate a DC discharge that features a power of 126 W and produces large amounts of OH radicals. The resulting PAW, after 5 min of SPED treatment, induces a slight acidification and increased concentrations of nitrate ions (from 24 to 250 mg l−1), nitrite ions (from less than 0.1 to 56.1 mg l−1) and hydrogen peroxide (from 0.3 to 18.5 mg l−1). Results indicate that DAP applied on maize seeds for 20 min boosts their germination rate by up to 90% (versus only 65% for untreated seeds) while reducing the median germination time by 37.5%. Then, seedling growth monitoring is achieved on control, DAP, PAW and DAP + PAW groups to assess stem length, hypocotyl length, leaf count, collar diameter and fresh/dry mass. The DAP + PAW group shows the most robust growth, demonstrating a synergistic effect of the combined treatments, particularly with significantly longer stem lengths. Additionally, physiological analyses of seedling leaves indicate a decrease in chlorophyll content despite enhanced growth, while fluorescence microscopy reveals a reduction in stomatal density in leaves treated with DAP and PAW, especially in the combined treatment group, potentially impacting photosynthetic efficiency and water regulation.

De novo strategy of organic semiconducting polymer brushes for NIR-II light-triggered carbon monoxide release to boost deep-tissue cancer phototheranostics.

The integration of photoacoustic imaging (PAI) and photothermal therapy (PTT) within the second near-infrared (NIR-II) window, offering a combination of high-resolution imaging and precise non-invasive thermal ablation, presents an attractive opportunity for cancer treatment. Despite the significant promise, the development of this noninvasive phototheranostic nanomedicines encounters challenges that stem from tumor thermotolerance and limited therapeutic efficacy. In this contribution, we designed an amphiphilic semiconducting polymer brush (SPB) featuring a thermosensitive carbon monoxide (CO) donor (TDF-CO) for NIR-II PAI-assisted gas-augmented deep-tissue tumor PTT. TDF-CO nanoparticles (NPs) exhibited a powerful photothermal conversion efficiency (43.1%) and the capacity to trigger CO release after NIR-II photoirradiation. Notably, the liberated CO not only acts on mitochondria, leading to mitochondrial dysfunction and promoting cellular apoptosis but also hinders the overexpression of heat shock proteins (HSPs), enhancing the tumor's thermosensitivity to PTT. This dual action accelerates cellular thermal ablation, achieving a gas-augmented synergistic therapeutic effect in cancer treatment. Intravenous administration of TDF-CO NPs in 4T1 tumor-bearing mice demonstrated bright PAI signals and remarkable tumor ablation under 1064nm laser irradiation, underscoring the potential of CO-mediated photothermal/gas synergistic therapy. We envision this tailor-made multifunctional NIR-II light-triggered SPB provides a feasible approach to amplify the performance of PTT for advancing future cancer phototheranostics.

Iron-based MOF with Catalase-like activity improves the synergistic therapeutic effect of PDT/ferroptosis/starvation therapy by reversing the tumor hypoxic microenvironment.

Reversing the hypoxic microenvironment of tumors is an important method to enhance the synergistic effect of tumor treatment. In this work, we developed the nanoparticles called Ce6@HGMOF, which consists of a photosensitizer (Ce6), glucose oxidase (GOX), chemotherapy drugs (HCPT) and an iron-based metal-organic framework (MOF). Ce6@HGMOF can consume glucose in tumor cells through "starvation therapy", cut off their nutrition source, and produce gluconic acid and hydrogen peroxide (H2O2). Utilizing this feature, Ce6@HGMOF can produce oxygen through catalase-like catalytic activity, thereby reversing the hypoxic microenvironment of tumors. This strategy of changing the hypoxic environment can help to slow down the growth of tumor blood vessels and improve the drug-resistant microenvironment to some extent. Meanwhile, increasing the supply of oxygen can enhance the effect of photodynamic therapy (PDT) and enhance the oxidative stress damage caused by reactive oxygen species (ROS) in tumor cells. On the other hand, cancer cells usually produce higher levels of glutathione (GSH) to adapt to high oxidative stress and protect themselves. The Ce6@HGMOF we designed can also consume GSH and induce ferroptosis of tumor cells through Fenton reaction with H2O2, while enhancing the effect of PDT. This innovative synergistic strategy, the combination of PDT/ferroptosis /starvation therapy, can complement each other and enhance each other. It has great potential as a powerful new anti-tumor paradigm in the future.

CTNI-25. TUMOR TREATING FIELDS (TTFIELDS) THERAPY WITH CHEMORADIATION, FOLLOWED BY MAINTENANCE TTFIELDS THERAPY/TEMOZOLOMIDE (TMZ), IN NEWLY DIAGNOSED GLIOBLASTOMA (NDGBM). RESULTS OF PHASE II CLINICAL STUDY

Abstract INTRODUCTION Tumor-Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cancer cell function and tumor progression via a multimodal mechanism of action. Following the phase 3 pivotal EF-14 study, TTFields therapy concomitant with temozolomide (TMZ) maintenance therapy became approved for newly-diagnosed glioblastoma (ndGBM). Pre-clinical data and pilot clinical studies suggests synergistic effect of concomitant TTFields treatment with radiotherapy (RT). OBJECTIVE To assess the efficacy and safety of first line TTFields therapy concomitant with RT/TMZ vs RT/TMZ alone in adult patients with ndGBM. Design: 69 patients with ndGBM and KPS≥70 stratified by MGMT status, extent of resection, and age, were randomized 1:1. The experimental arm received TTFields therapy from the first day of chemoradiation, the control arm started 4 weeks after completion of chemoradiation. Patients continued TTFields therapy until second disease progression or 24months. The primary endpoint was 1-year PFS rate, and secondary endpoints included PFS, OS, and safety. Kaplan-Meier estimates were used to assess whether PFS and OS were improved with first line TTFields therapy/RT/TMZ vs RT/TMZ with delayed TTFields therapy. RESULTS Overall, 46 patients received maintenance chemotherapy and TTFields therapy. Mean age was 62 years (range:27–77). One-year PFS rate was 36% and 19% in the experimental and control arms, respectively (p-value=0.10). Median PFS was 9.9 and 5.6 months (HR 0.53, p-value 0.049). Median OS was 25.9 and 17 months (HR 0.85, p-value=0.6). Two-year OS rates were 52% and 31% (p-value 0.07). Among patients with high TTFields usage (≥75%) 2-year OS rates were 78% and 34% (p=0.01). CONCLUSIONS The addition of concomitant TTFields to standard treatment with temozolomide and RT for patients with ndGBM appears to be another step in improving the outcome of this patients population. This is further investigated in the large-scale TRIDENT study.

TMET-18. MANNOSE INHIBITS GLIOMA CELL PROLIFERATION AND POTENTIATES TEMOZOLOMIDE EFFICACY

Abstract Gliomas are among the most aggressive types of brain tumors, often displaying resistance to standard therapies such as temozolomide (TMZ). Recent research suggests that metabolic modulation may influence tumor growth and therapeutic response. This study explores the effects of mannose, a monosaccharide, on glioma cell growth and its potential to enhance the efficacy of TMZ. In vitro experiments were conducted to evaluate the impact of mannose and its combination with TMZ on glioma cells. Cell viability assays, ATP measurements, and flow cytometry (FACS) analysis were performed to assess cell cycle and apoptosis post-treatment with various monosaccharides, including mannose. The synergistic effects of the combined treatment with mannose and TMZ on cell viability were evaluated using Bliss score analysis and FACS. The impact on cancer stem cell characteristics was investigated through neurosphere formation assays, while tumor invasiveness was assessed using 3D invasion assays. Expression of stemness and invasion markers was analyzed by western blot. Differentially expressed gene (DEG) analysis was conducted to assess changes in gene expression related to stemness and invasiveness. Mannose treatment significantly reduced glioma cell viability and ATP levels, indicating decreased metabolic activity. Combined treatment with mannose and TMZ demonstrated a synergistic effect, enhancing cell death compared to either treatment alone, as evidenced by Bliss score and FACS analysis. Co-treatment reduced neurosphere formation and 3D invasion capabilities, with western blot results showing downregulation of stemness and invasion markers. DEG analysis revealed significant changes in gene expression related to stemness and invasiveness with the combined treatment. Mannose significantly impairs glioma cell growth and enhances the therapeutic efficacy of TMZ in vitro. Combining mannose with standard chemotherapy offers a promising strategy for improving glioma treatment outcomes. Further investigation in clinical settings is warranted to validate these findings.

SYNERGISTIC EFFECT LUNG CANCER THERAPY: CO-DELIVERY OF QUERCETIN AND CISPLATIN VIA EUDRAGIT L-100 NANOPARTICLES IN VITRO

Objective: This study aims to investigate the potential of Eudragit L-100 nanoparticles for the co-delivery of quercetin and cisplatin to lung cancer cells, seeking to exploit the synergistic effects of the two drugs while overcoming their individual limitations. Methods: We investigate the synergistic effect of co-delivering quercetin and cisplatin using Eudragit L-100 nanoparticles for lung cancer therapy. The nanoparticles were synthesized using the nanoprecipitation method, where Eudragit L-100 was dissolved in an organic solvent, followed by the incorporation of quercetin and cisplatin. The resultant nanoparticles were characterized for size, zeta potential, drug loading efficiency, and morphology using techniques such as Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). Results: The co-loaded Quercetin-Cisplatin Nanoparticles (Qu-Cis)-NPs formulation had a mean particle size of 475±4.77 nm. Polydispersion index of 0.266±0.093 and zeta potential was-24.03±0.89 mV. The in vitro cytotoxicity was assessed using normal cell and lung cancer cell lines in vitro studies showed that the developed nanoparticles significantly increased cancer cell mortality compared to individual drug treatments. The combination (Qu-Cis)-NPs showed more cytotoxicity on the Non-Small Lung Cancer Cell Line (NCI-H460) cancer cell line after 48 h of incubation compared to Qu loaded-NPs and Cis loaded-NPs, particularly at a concentration of 1 mg/ml. The combination showed no cytotoxicity effect on normal Human Lung fibroblast cell Lines (CCD-19 lu) cells at all concentrations after 24 h, but showed cytotoxicity effects at concentrations (0.125, 0.25, 0.5, and 1.0) mg/ml after 48 h. Conclusion: The Eudragit L-100 nanoparticle system for co-delivering quercetin and cisplatin showed a promising synergistic effect in lung cancer treatment. It effectively addresses the solubility and toxicity issues of both drugs, offering a potentially more effective treatment option that merits further clinical investigation.

The waste recycling approach for enhancing wastewater sludge dewaterability by using iron-mud (IM)/sawdust derived carbon composite

The dewaterability of wastewater sludge by the solid waste of iron-mud (IM)/carbon (IMS) composite prepared via the in-situ carbothermal reduction method was systematically studied in this paper. It investigated the effects of different IMS materials, IM dosages and stirring speeds on sludge dewaterability, including water content (WC), capillary suction time (CST), extracellular polymeric substances (EPS) contents and particle size. The results of dewatering tests demonstrated that IMS materials significantly enhanced sludge dewaterability, resulting in a reduction of 39.85% in CST and 13.26% reduction in WC in the dewatered sludge under optimum condition (IMS-3 dosage of 8% dry solids; stirring speed of 250 r/min for 30 minutes). Electron paramagnetic resonancec (EPR) and scavenging experiments were conducted to better understand the dewatering process mechanism. This results indicated that both hydroxyl radicals (•OH) and superoxide radicals (•O2−) collaborate during the dewatering process. Furthermore, analysis were performed on the particle size of sludge flocs and scanning electron microscopy (SEM) imaging of sludge morphology to reveal the synergistic effects of IMS treatment. A two-step mechanism involving oxidation and Fe(III)-based re-flocculation maybe explain the synergistic effect of IMS treatment. This novel recycle-based IMS composite approach offers a new management strategy for industrial solid wastes while enhancing the sludge dewatering efficiency.

Synergistic effects of combined hyperthermia and electric fields treatment in non-small cell lung-cancer (NSCLC) cell lines.

Lung cancer remains a leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) being particularly challenging due to poor survival rates, emphasizing the need for new treatments. This study examined the therapeutic effects of combining hyperthermia (HT) with tumor-treating electric fields (TTF) in NSCLC. Cells were exposed to four different conditions: hyperthermia at 42°C for 30min, electric fields at 150kHz and 0.8V/cm for 24h, a combination of both treatments, or no treatment (control). Cell proliferation was measured using WST and colony-formation assays, while apoptosis, DNA damage, and repair protein levels were analyzed via Western blotting. Metastatic potential was evaluated with a transwell assay, and cell migration was assessed using the wound-healing assay. The combination therapy significantly inhibited colony formation and reduced cell migration and invasion more effectively than individual treatments. The combined treatment also enhanced apoptosis, as indicated by increased cleaved-PARP and Annexin V levels. In addition, the DNA-damage marker γ-H2AX was elevated, while BRCA1, a protein involved in DNA repair, was significantly downregulated compared to the individual treatments. These results suggest that the enhanced anticancer effects of HT and TTF are due to increased DNA damage and suppression of DNA-repair mechanisms, highlighting the potential of this combination therapy for NSCLC treatment.

Synergistic effects of alkaline and heat treatments on structural and functional properties of mung bean protein isolate: improving physicochemical stability of plant‐based emulsions

SummaryPlant‐based meat alternatives often require fat replacers to mimic the texture of traditional products. This study aimed to develop plant‐based emulsion gels using mung bean protein isolate (MBPI) as a potential fat substitute. However, creating these gels via heat setting requires a high protein concentration, which demands modification of the MBPI structure to enhance emulsifying properties. This study investigated synergistic effects of alkaline treatment (0.3 or 3.5% Na2CO3) and heat treatments (40 or 70 °C) on the functional properties of MBPI at high protein levels, for potential application as a plant‐based emulsion. The combined treatments reduced the zeta potential of protein suspensions from −9 to −19 mV and altered the protein conformation to form smaller particles (from 426 to 166 μm) with increased β‐sheet content. These treatments improved dispersibility of 8% MBPI suspension (58 to 86%), emulsifying activity index (6.34–10.89 m2 g−1), and stability coefficient (43 to 96%). Notably, MBPI samples treated with 0.3% Na2CO3 at 40 and 70 °C exhibited excellent emulsifying properties, forming stable monolayers at the oil–water interface, likely due to the increased surface activity of MBPI. Increasing protein concentration to 11% facilitated heat‐set gel formation; however, addition of 3.5%‐Na2CO3 induced premature gelation, limiting its application in emulsions. At 0.3%‐Na2CO3, increasing the protein content from 8% to 11% and the oil content from 10% to 30% further reduced emulsion droplet size, especially for MBPI treated with 0.3% Na2CO3 at 70 °C (MB‐0.3%‐70 °C) from 5.10 to 2.61 μm, likely due to decreased coalescence. This treatment yielded superior MBPI‐stabilised emulsion gels with enhanced penetration, fluid retention, and stability by possibly reducing protein aggregation. These findings demonstrate the potential of MBPI modified by combined addition of 0.3% Na2CO3 and heat treatment, particularly MB‐0.3%‐70 °C, as a promising ingredient for producing plant‐based emulsions.

Synergistic Effect of Chemical and Physical Treatments on Azolla pinnata for Cadmium Ions Removal from Synthetic Wastewater Systems

Synergistic Effect of Chemical and Physical Treatments on Azolla pinnata for Cadmium Ions Removal from Synthetic Wastewater Systems

State-of-the-art application of nanoparticles in radiotherapy: aplatform for synergistic effects in cancer treatment.

Radiotherapy (RT) is agold standard cancer treatment worldwide. However, RT has limitations and many side effects. Nanoparticles (NPs) have exclusive properties that allow them to be used in cancer therapy. Consequently, the combination of NP and RT opens up anew frontier in cancer treatment. Among NPs, gold nanoparticles (GNPs) are the most extensively studied and are considered ideal radiosensitizers for radiotherapy due to their unique physicochemical properties and high X‑ray absorption. This review analyzes the various roles of NPs as radiosensitizers in radiotherapy of glioblastoma (GBS), prostate cancer, and breast cancer and summarizes recent advances. Furthermore, the underlying mechanisms of NP radiosensitization, including physical, chemical, and biological mechanisms, are discussed, which may provide new directions for next-generation GNP optimization and clinical transformation.

Gradual Optimization of Molecular Aggregation and Stacking Enables Over 19% Efficiency in Binary Organic Solar Cells.

Volatile solid additive is an effective and simple strategy for morphology control in organic solar cells (OSCs). The development of environmentally friendly new additives which can also be easily removed without high-temperature thermal annealing treatment is currently a trend, and the working mechanism needs to be further studied. Herein, a highly volatile and non-halogenated solid additive 1-benzothiophene (BBT) is reported to regulate molecular aggregation and stacking of active layer components. According to the film-forming kinetics process, a momentary intermediate phase is formed during spin-coating, which slows down the film-forming process and leads to more ordered molecular stacking in the solid film after introducing solid additive BBT. Subsequently, after solvent vapor annealing (SVA) further treatment, the resultant blend films exhibit a tighter and more ordered molecular stacking. Consequently, the synergistic effect of solid additive BBT and SVA treatment can effectively control morphology of active layer and improve carrier transport characteristics, thereby enhancing the performance of OSCs. Finally, in D18-Cl:N3 system, an impressive power conversion efficiency of 19.53% is achieved. The work demonstrates that the combination of highly volatile solid additives and SVA treatment is an effective morphology control strategy, guiding the development of efficient OSCs.

A stimuli-responsive keratin functionalized PEI coated baicalin nano-hydrogels for modulated gastric ulcer therapy

Nano-hydrogel system conjugated with polymer like polyethylieneimine offers a significant attention in the field of healthcare owing to their significant pH-specific swelling behaviour in acidic medium. The focus of this research work was to fabricate a stable and non-toxic, keratin-PEI coated nano-hydrogel formulation exhibiting synergistic effect for gastric ulcer treatment. K-PEI-BL nano-hydrogel shows particle size ~500nm with polydispersity index 0.473 ± 0.04, zeta potential of 15.4 ± 6.06mV, entrapment efficiency of 91.94 ± 0.04% and in vitro controled release of 72.78 ± 0.52% for 24h in pH 1.2. Scanning electron miscroscopy (SEM), Transmission electron microscopy (TEM) images confirmed the morphological structure of double coated nano-hydrogel particle. Ex-vivo mucoadhesive study of keratin-PEI coated-BA-NH formulation at gastric ulcer site exhibited 21h and 15min as a residence time in comparison to uncoated BA-NH formulation. In-vivo analysis displayed improvenent in ulcer treatment compared to negative control group with 86.46% and 71.86% inhibition of ulcer in standard ranitidine and K-PEI-BL nano-hydrogel treatment groups, respectively. This research study concluded that K-PEI-BL nano-hydrogel formulation with 15mg/kg dose exhibited anti-ulcer actions by reducing the severity of gastric abrasions.

Synergistic Effects of Surface Texture and Cryogenic Treatment on the Tribological Performance of Aluminum Alloy Surfaces

In order to improve the tribological properties of the 7075-T6 aluminum alloy used on the rotor surface, a combined method of cryogenic treatment and laser surface texture treatment was applied. Various tests, including metallographic microscopy, scanning electron microscopy, elemental analysis, microhardness measurements, were conducted to examine the wear morphology and modification mechanism of the treated 7075-T6 aluminum alloy surface. A numerical simulation model of surface texture was established using computational fluid dynamics to analyze the lubrication characteristics of V-shaped texture. The research finding that the 7075-T6 aluminum alloy experienced grain refinement during the cryogenic treatment process, enhancing the wear resistance of the V-shaped textures. This improvement delayed the progression of fatigue wear, abrasive wear, and oxidative wear, thereby reducing friction losses. The designed V-shaped texture contributes to reducing contact area, facilitating the capture and retention of abrasives, and enhancing oil film load-bearing capacity, thereby improving tribological performance. The synergistic effect of cryogenic treatment reduced the friction coefficient by 24.8% and the wear loss by 66.4%. Thus, the combination of surface texture and cryogenic treatment significantly improved the tribological properties of the 7075-T6 aluminum alloy.

Ultrasound-assisted fungal self-growth and heteroatom doping for the preparation of high-performance lignocellulose-based supercapacitor electrodes

Biomass materials are widely used as supercapacitor electrode materials due to their cost-effectiveness and eco-friendliness. In this work, ultrasound-assisted impregnation was employed for the thorough mixing of the liquid medium, and fungal treatment was conducted on the three main components of lignocellulose to prepare a fungi-modified heteroatom-doped lignocellulose-based carbon material (LCF-NP). The effects of heteroatom doping, the content of the three main components, and fungal modification on the electrochemical performance of lignocellulose-based carbon materials was investigated. The results revealed the synergistic effect of heteroatom doping and fungal treatment on the electrochemical performance. Compared with its counterpart free of fungal treatment, LCF-NP has a more reasonable pore structure and exhibits excellent electrochemical performance. LCF-NP porous carbon material has the highest specific surface area (792 m2/g), large pore volume (0.523 cm3/g), and ideal specific capacitance (1940 mF/cm2) under the conditions of 1.0 M Na2SO4 electrolyte and current density of 0.5 mA/cm2. After 10,000 cycles, there is almost no loss of capacitance. These results indicate that the joint utilization of heteroatom doping and fungal treatment has a promising application prospect in pore structure regulation and electrochemical performance improvement. This study provides a new strategy for the preparation of lignocellulose-based carbon electrode materials.

Fibroblast Growth Factor 2 (FGF2) Activates Vascular Endothelial Growth Factor (VEGF) Signaling in Gastrointestinal Stromal Tumors (GIST): An Autocrine Mechanism Contributing to Imatinib Mesylate (IM) Resistance.

We showed previously that the autocrine activation of the FGFR-mediated pathway in GIST lacking secondary KIT mutations was a result of the inhibition of KIT signaling. We show here that the FGF2/FGFR pathway regulates VEGF-A/VEGFR signaling in IM-resistant GIST cells. Indeed, recombinant FGF2 increased the production of VEGF-A by IM-naive and resistant GIST cells. VEGF-A production was also increased in KIT-inhibited GIST, whereas the neutralization of FGF2 by anti-FGF2 mAb attenuated VEGFR signaling. Of note, BGJ 398, pan FGFR inhibitor, effectively and time-dependently inhibited VEGFR signaling in IM-resistant GIST T-1R cells, thereby revealing the regulatory role of the FGFR pathway in VEGFR signaling for this particular GIST cell line. This also resulted in significant synergy between BGJ 398 and VEGFR inhibitors (i.e., sunitinib and regorafenib) by enhancing their pro-apoptotic and anti-proliferative activities. The high potency of the combined use of VEGFR and FGFR inhibitors in IM-resistant GISTs was revealed by the impressive synergy scores observed for regorafenib or sunitinib and BGJ 398. Moreover, FGFR1/2 and VEGFR1/2 were co-localized in IM-resistant GIST T-1R cells, and the direct interaction between the aforementioned RTKs was confirmed by co-immunoprecipitation. In contrast, IM-resistant GIST 430 cells expressed lower basal levels of FGF2 and VEGF-A. Despite the increased expression VEGFR1 and FGFR1/2 in GIST 430 cells, these RTKs were not co-localized and co-immunoprecipitated. Moreover, no synergy between FGFR and VEGFR inhibitors was observed for the IM-resistant GIST 430 cell line. Collectively, the dual targeting of FGFR and VEGFR pathways in IM-resistant GISTs is not limited to the synergistic anti-angiogenic treatment effects. The dual inhibition of FGFR and VEGFR pathways in IM-resistant GISTs potentiates the proapoptotic and anti-proliferative activities of the corresponding RTKi. Mechanistically, the FGF2-induced activation of the FGFR pathway turns on VEGFR signaling via the overproduction of VEGF-A, induces the interaction between FGFR1/2 and VEGFR1, and thereby renders cancer cells highly sensitive to the dual inhibition of the aforementioned RTKs. Thus, our data uncovers the novel mechanism of the cross-talk between the aforementioned RTKs in IM-resistant GISTs lacking secondary KIT mutations and suggests that the dual blockade of FGFR and VEGFR signaling might be an effective treatment strategy for patients with GIST-acquired IM resistance via KIT-independent mechanisms.

Today's cancer research and treatment - highly sophisticated and molecularly targeted, yet firmly bolstered in the classical theories.

Cancer research is linked to modern life-sciences, encompassing achievements in virology, yeast-biology, molecular-biology, genetics, systems-biology, bioinformatics, and so on. With these fascinating developments, it's easy to overlook that the fundamental theories and treatment strategies were established in the early 20th century and have remained valid ever since. Therefore, tribute must be paid to the founders of the field. The main hypotheses on carcinogenesis, the genetic model and the metabolic model, and the concept of cancer-treatment with cytotoxic, targeted or metabolic drugs were proposed more than 100 years ago by great minds such as T. Boveri, O. Warburg, and P. Ehrlich. Hence nothing about these cancer concepts is really new. Through development of powerful new technologies, we have been able to decipher the mechanisms of malignant transformation, thus significantly advancing the field. Our own studies have been focused on the cross-talk between cell-growth-signaling and lipid-metabolism in ovarian cancer to find crossover-points for co-targeting in order to achieve synergistic treatment effects. Notably, a side-effect of the application of current methods of molecular-cell-biology is a deeper knowledge of the laws of normal cell-biology and cell-life. Thus we anticipate the field will advance rapidly in the near future.

Pharmacodynamic interaction between tamsulosin and finasteride treatment in mice induced benign prostate hyperplasia using the Chou-Talalay method

This study was conducted to evaluate the efficacy and interaction of tamsulosin with finasteride treatment on induced benign prostate hyperplasia (BPH) in mice. BPH was induced by subcutaneous injection of testosterone propionate (20 mg/kg) for 30 days. Eighty-five mice were divided into five groups. The first group (G1): twenty-five mice induced BPH treated with tamsulosin orally and divided into five equal subgroups with doses (0.017, 0.052, 0.087, 0. 123, and 0.158) mg/kg, the second group (G2): twenty-five mice induced BPH treated with finasteride orally and divided into five equal subgroups with doses (0.175, 0.527, 0.878, 1.23, and 1.580) mg/kg, the third group (G3): twenty-five mice induced BPH treated with a combination of tamsulosin with finasteride orally, and divided into five equal subgroups with doses (0.0085, 0.0875), (0.026, 0.2635), (0.0435, 0.439) , (0.0615, 0.615) and ( 0.079 , 0.790 ) mg/kg respectively. Fourth group (G4): five mice induced BPH and treated distilled water. Fifth group (G5): five mice were not inducing BPH and without any treatment. The results showed a gradual significant increase in prostate weight % and prostate index % inhibitions until reached saturation in the last two doses of tamsulosin, finasteride, and combination groups, the maximum effective doses of tamsulosin and finasteride were (0.156) and (1.495) mg/kg respectively. Moreover, the effective dose of the combination (tamsulosin and finasteride) was estimated (0.06876, 0.6876) mg/kg respectively as well as the type of interaction was synergism and the value of the combination index was 0.046. The combination of tamsulosin with finasteride showed a synergistic effect in BPH treatment by minimizing the side effect of each drug as a result of decreasing the dose of each one.

Fabrication of acorn-shaped Janus C-SiO2 carrier and their application in DOX release

Asymmetric nanocarriers with different functions can achieve synergistic effect in cancer treatment. In this study, asymmetric carbon-silica (C-SiO2) carriers were prepared for drug delivery and combining therapy. The C-SiO2 carriers presented acorn-like structure with dendritic mesoporous silica hat and carbon body. The carbon body render the carriers photothermal effect. The prepared C-SiO2 carriers with size around 130 nm have improving cell uptake efficiency, and excellent biocompatibility. After loading doxorubicin hydrochloride (DOX), menthol (LM) was used to seal the loaded drug (DOX@C-SiO2-LM). LM coating can melt above the phase transition temperature, leading to the release of loaded cargo. The DOX@C-SiO2-LM displayed temperature/NIR-triggered drug release.

Tubeimoside-I, an inhibitor of HSPD1, enhances cytotoxicity of oxaliplatin by activating ER stress and MAPK signaling pathways in colorectal cancer

Ethnopharmacological relevanceTubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood. Aim of the studyTo elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity. Materials and methods3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin. ResultsThe synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone. ConclusionsCombined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients.