Strategy For Treatment Of Tumors Research Articles

A case of successful conversion surgery for locally advanced pancreatic cancer with synchronous triple cancer of the lung and esophagus: a case report

BackgroundThe number of reports of multiple primary cancer (MPC) is increasing because of the advancement in diagnostic imaging technology. However, the treatment strategy for MPCs involving pancreatic cancer is controversial because of the extremely poor prognosis. We herein report a patient with synchronous triple cancer involving the pancreas, esophagus, and lung who underwent conversion surgery after intensive chemotherapy for unresectable locally advanced pancreatic cancer.Case presentationA 59-year-old man was admitted to our hospital with epigastric pain, anorexia, and weight loss. Computed tomography and upper gastrointestinal endoscopy revealed that the patient had synchronous triple cancer of the pancreas, esophagus, and lung. While the esophageal and lung cancer were relatively non-progressive, the pancreatic tail cancer had invaded the aorta, celiac axis, and left kidney, and the patient was diagnosed with unresectable locally advanced disease. Because the described lesion could have been the prognostic determinant for this patient, we initiated intensive chemotherapy (gemcitabine plus nab-paclitaxel) for pancreatic cancer. After six courses of chemotherapy, the tumor size shrank remarkably and no invasion to the aorta or celiac axis was observed. No significant changes were observed in the esophageal and lung cancers; endoscopic submucosal dissection could be still a curative treatment for the esophageal cancer. Therefore, we performed curative resection for pancreatic cancer (distal pancreatomy, splenectomy, and left nephrectomy; ypT3N0cM0, ypStage IIA, UICC 8th). Pathologically, complete resection was achieved. The patient then underwent endoscopic submucosal dissection for early esophageal cancer (pT1a[M]-LPM) and video-assisted thoracoscopic right upper lobectomy in combination with right lower partial resection for early lung cancer (pT2aN0M0, pStage IB, UICC 8th). Eight months after pancreatic cancer surgery, the patient is alive and has no sign of recurrence; as a result of the successful treatment, the patient has a good quality of life.ConclusionsTreatment of MPC is challenging, especially for cases with unresectable tumors. Although synchronous triple cancer can involve unresectable pancreatic cancer, radical resection may be possible after careful assessment of the appropriate treatment strategy and downstaging of unresectable tumors.

Oleanolic acid-conjugated human serum albumin nanoparticles encapsulating doxorubicin as synergistic combination chemotherapy in oropharyngeal carcinoma and melanoma

Combination chemotherapy produces a superior therapeutic response than monotherapy in cancer. Human serum albumin and a naturally occurring cancer prophylactic/anticancer triterpenoid, oleanolic acid, were conjugated to form self-assembled nanoparticles that entrapped doxorubicin. Dox@HSA-OA NPs were physicochemically characterized for particle size, zeta potential, drug loading, entrapment efficiency, stability, release, and hemocompatibility. The Dox@HSA-OA NPs (particle size. ∼ 140 nm) showed commendable loading (14.6 %), entrapment (59.01%) of Dox. The in vitro cell uptake study using human oral squamous carcinoma (FaDu-HTB-43) and murine melanoma (B16F10) cells indicated a higher cellular association of Dox@HSA-OA NPs than free Dox. The lowest IC50 of Dox@HSA-OA NPs than Dox against both the cell lines at various time points proved the Dox/HSA-OA-mediated combination chemotherapeutic effect. Dox@HSA-OA NPs demonstrated higher apoptosis and cell cycle arrest (G2/M phase). The Dox@HSA-OA NPs-mediated Dox penetration, cell death/shrinkage were significant in FaDu-HTB-43 spheroids. Dox@HSA-OA NPs showed a better pharmacokinetic profile with increased t1/2 and Cmax than Dox. The in vivo experiment using B16F10 tumor-bearing mice showed tumor regression, DNA damage, oxidative stress, and apoptosis-induction via the intrinsic pathway to a greater extent following Dox@HSA-OA NPs treatment than Dox. Therefore, the Dox@HSA-OA NPs-mediated combination therapy could be a powerful treatment strategy for solid tumors.

PUTH Grading System for Urinary Tumor With Supradiaphragmatic Tumor Thrombus: Different Surgical Techniques for Different Tumor Characteristics.

PurposeTo explore the different treatment strategies for urinary tumors with Mayo IV thrombus.Materials and MethodsWe retrospectively analyzed the patients with Mayo IV thrombus in Peking University Third Hospital from January 2014 to April 2021. We used the Peking University Third Hospital (PUTH) grading system to classify urinary tumors with supradiaphragmatic thrombus. PUTH-A referred to the filled thrombus whose tip just reached above the diaphragm, or the thrombus entering the right atrium (< 2cm). PUTH-B referred to the filled thrombus entering the right atrium (> 2cm), or the thrombus invading the wall of the inferior pericardial vena cava. Detailed techniques were described for various scenarios. Clinicopathological data and perioperative outcomes were reported. Group difference statistical analysis was performed.ResultsA total of 26 cases of urinary tumors with supradiaphragmatic IVC thrombus (Mayo grade IV) underwent treatment were enrolled in this study. 19 patients in the PUTH-A group received the open approach without sternotomy and cardiopulmonary bypass. Seven patients in the PUTH-B group received open thoracotomy assisted by cardiopulmonary bypass. No intraoperative death occurred. After 56 months of follow-up, 46.2% (12 of 26) patients died of all causes. Estimated 1-year, 2-year, and 3-year overall survival were 72.0% (95% CI, 54.4%-89.6%), 58.2% (95% CI, 38.0%-78.4%), and 52.4% (95% CI, 31.2%-73.6%), respectively.ConclusionsWe introduced the PUTH grading system for the characteristics of urinary tumors with supradiaphragmatic tumor thrombus, and selected different surgical techniques according to different classifications. This grading system was relatively feasible and effective.

Exosome-based rare earth nanoparticles for targeted in situ and metastatic tumor imaging with chemo-assisted immunotherapy.

In this research, a tumor exosome system DOX/2DG@E-RENPs with good biocompatibility, low immunogenicity, and a high targeting effect was proposed for theranostics with high chemo-/starvation/immunotherapy efficiency. DOX and 2-deoxy-D-glucose (DOX/2DG) together with rare earth nanoparticles (RENPs) can be simultaneously carried on the exosome by endocytosis of tumor cells and then exocytosis in vitro. This platform has a good monodispersity with an average size of 70 nm, and the system can emit upconversion luminescence and NIR II luminescence under a single NIR laser. In particular, this exosome can target homing cancer cells and kill the origin tumor cells. The strong targeting effect was proved by different cell lines with exosomes from different orthogonal cells (normal/cancer cells and human/mouse sources, respectively), and the in vivo NIR II imaging guided targeted cancer imaging and liver metastases can be realized by intravenous injection of E-RENPs. Furthermore, the good targeted therapeutic effect and in vivo NIR II imaging and metastases of this platform can be proved. The chemotherapy, starvation therapy, and immunotherapy (immune checkpoint inhibitors of an anti-PD-L1 antibody) could achieve effective synergistic therapy for lung adenocarcinoma, and the immunotherapy can be further proved by the clinical data. This will provide a new strategy for the precise targeting and treatment of tumors.

Effective Dose Fractionation Schemes of Radiotherapy for Prostate Cancer

Radiation therapy has remained as one of the main cancer treatment modalities and a highly cost-effective single modality treatment of cancer care. Typical regimens for fractionated external beam radiotherapy comprise a constant dose administered on weekdays, and no radiation on weekends. However, every patient has a tumor with distinct properties depending on intra-tumor heterogeneity, aggressiveness, and interactive properties with other cells that may make it more resistant or sensitive to radiation treatment. Accordingly, the concept of personalized cancer treatment is emerging to specialize each patient treatment case to the unique properties of the tumor. In this paper, we examine adaptive radiation treatment strategies for heterogeneous tumors using a dynamical system model that consists of radiation-resistant and parental cell populations with unique interactive properties. We study different adaptive dosage strategies for PC3 and DU145 prostate cancer cell lines. We show that stronger doses of radiation given in longer time intervals, while keeping the overall dosage the same, reduce final tumor volume by more than half in PC3 cell lines, but by only five percent in DU145 cell lines. In addition, we tested an adaptive dosing schedule by administering a stronger dosage on Friday to compensate for the treatment-off period during the weekend, which was effective in decreasing the final tumor volume of both cell lines. This result creates interesting possibilities for new radiotherapy strategies at clinics that cannot provide treatment on weekends. Finally, we propose a dosage plan incorporating our findings.

Usefulness of Oxidized Regenerated Cellulose Powder in stopping bleeding during laparoscopic ovarian cystectomy to protect ovarian reserve

Objective: The treatment strategy for ovarian tumors is often uncertain when a patient wishes to have children. Especially in the case of endometriotic cysts, although pre-assisted reproductive technology ovarian cystectomy does not improve the live birth rate, surgery may be selected considering the symptom and the infertility treatment course. In such cases, it is necessary to pay attention to selecting the hemostatic method for ovarian reserve. It has been reported that hemostasis with suture / hemostatic sealant has a smaller decrease in serum anti-Müllerian hormone (AMH) level than with bipolar coagulation. We focused on this method using a hemostatic sealant.

Treatment strategies for metastatic spinal tumors of the craniovertebral junction

Treatment strategies for metastatic spinal tumors of the craniovertebral junction

HKUST-1 nano metal-organic frameworks combined with ZnGa2O4:Cr3+ near-infrared persistent luminescence nanoparticles for in vivo imaging and tumor chemodynamic and photothermal synergic therapy.

The multifunctional theranostic nanoplatform based on the combination of persistent luminescent nanoparticles (PLNPs) and metal-organic frameworks (MOFs) has both in vivo imaging and tumor therapeutic drug-loading functions, providing a new strategy for accurate and effective tumor diagnosis and treatment. Herein, the near-infrared (NIR) PLNP SiO2@Zn1.05Ga1.9O4:Cr was combined with HKUST-1 MOFs to form a core-shell structure theranostic nanoplatform which possessed the triple function of autofluorescence-free NIR PersL bioimaging, tumor chemodynamic therapy (CDT), and tumor photothermal therapy (PTT). Also, the photothermal conversion efficiency reached 58.7%, which is superior to the reported nano metal-organic framework (NMOF) photothermal reagents. We demonstrated that the nanoplatform could enter the tumors of mice within 0.5 h and could be target-activated by H2O2 and H2S in the tumor cells, resulting in effective PTT and CDT synergistic treatment. Tumor-bearing mice experiments showed that the tumor could be completely cured without harming normal tissue. This theranostic nanoplatform may provide a promising strategy showing imaging, PTT, and CDT synergistic treatment tri-mode for clinical cancer therapy.

Challenges and opportunities to penetrate the blood-brain barrier for brain cancer therapy.

Despite significant advances in research, the prognosis for both primary and secondary brain cancers remains poor. The blood-brain barrier (BBB) is a complex and unique semi-permeable membrane that serves as a protective structure to maintain homeostasis within the brain. However, it presents a significant challenge for the delivery of therapeutics into the brain and tumor. Some brain tumors are known to compromise BBB integrity, producing a highly heterogeneous vasculature known as the blood-tumor-barrier (BTB). Identifying strategies to bypass these obstacles to improve the penetrability of anticancer therapeutics has been the focus of research in this area. In this review, we discuss the strategies that have been investigated to evade or alter the cellular and molecular barriers of both the BBB and the BTB and detail the methods currently under preclinical or clinical investigation, including molecular, biological, and physical processes to overcome the BBB or BTB. Increased understanding of the BBB and BTB and the current methods of overcoming these barriers will enable the development of new and more effective treatment strategies for brain tumors.

Establishment of Patient-Derived Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumor Models for Predicting Therapeutic Response.

Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract, with mutant succinate dehydrogenase (SDH) subunits (A-D) comprising less than 7.5% (i.e., 150-200/year) of new cases annually in the United States. Contrary to GISTs harboring KIT or PDGFRA mutations, SDH-mutant GISTs affect adolescents/young adults, often metastasize, and are frequently resistant to tyrosine kinase inhibitors (TKI). Lack of human models for any SDH-mutant tumors, including GIST, has limited molecular characterization and drug discovery. We describe methods for establishing novel patient-derived SDH-mutant (mSDH) GIST models and interrogated the efficacy of temozolomide on these tumor models in vitro and in clinical trials of patients with mSDH GIST. Molecular and metabolic characterization of our patient-derived mSDH GIST models revealed that these models recapitulate the transcriptional and metabolic hallmarks of parent tumors and SDH deficiency. We further demonstrate that temozolomide elicits DNA damage and apoptosis in our mSDH GIST models. Translating our in vitro discovery to the clinic, a cohort of patients with SDH-mutant GIST treated with temozolomide (n = 5) demonstrated a 40% objective response rate and 100% disease control rate, suggesting that temozolomide represents a promising therapy for this subset of GIST. We report the first methods to establish patient-derived mSDH tumor models, which can be readily employed for understanding patient-specific tumor biology and treatment strategies. We also demonstrate that temozolomide is effective in patients with mSDH GIST who are refractory to existing chemotherapeutic drugs (namely, TKIs) in clinic for GISTs, bringing a promising treatment option for these patients to clinic.See related commentary by Blakely et al., p. 3.

Polymeric indoximod based prodrug nanoparticles with doxorubicin entrapment for inducing immunogenic cell death and improving the immunotherapy of breast cancer.

Immunotherapy based on host immunity has emerged as a powerful therapeutic strategy for tumor treatment. However, utilizing the immune system against tumors often fails to result in a durable immune response due to insufficient immunogenicity and the immunosuppressive conditions in the tumor microenvironment. Herein, we developed prodrug-based nanoparticles (DOX/IND@NPs) for the codelivery of indoximod (IND), an indoleamine 2,3-dioxygenase (IDO) inhibitor that can block the IDO pathway and generate antitumor immunity, and doxorubicin, a DNA-damaging therapeutic agent that can induce tumor immunogenic cell death (ICD). The nanocarrier was designed for tumor chemoimmunotherapy, synergistically promoting immunogenicity and modulating the immunosuppressive tumor microenvironment (ITME). Our data showed that DOX induced tumor immunogenicity and increased the infiltration of CD8 + T cells into the tumor microenvironment; nevertheless, immunosuppressive immune cell components, such like regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor associated macrophages (TAMs), hindered the antitumor efficacy. The introduction of IND reduced the levels of these protumor immune cells within the tumor microenvironment and further enhanced CD8 + T cell infiltration and the CD8 +/Treg cell ratio. Moreover, significant reductions in vascular endothelial growth factor (VEGF), MMP9, and CD31 (a vascular marker) expression levels were observed after DOX-IND nanoparticle treatment. This resulted in obvious tumor regression in a murine breast cancer model compared to reference formulations, indicating that the codelivery of DOX and IND is a potent potential strategy for breast cancer chemoimmunotherapy.

Novel polysaccharide building hybrid nanoparticles: remodelling TAMs to target ERα-positive breast cancer

With the increasing number of oncology patients and the use of chemotherapeutic agents, tumour multidrug resistance is becoming more and more prevalent. The search for new tumour treatment strategies to overcome tumour multidrug resistance is urgent. In this study, we designed GSH and ROS dual-responsive tumour-associated macrophages (TAMs)-targeted nanoparticles (NPs) for the co-delivery of the clinical first-line anti-breast cancer chemotherapy drug paclitaxel (PTX) and baicalin (Bai), which re-educates TAMs to alter their phenotype. We synthesised oligohyaluronic acid-mannose-folic acid (oHA-Man-FA, HMF) and astragalus polysaccharide-dithiodipropionic acid-paeoniflorol (APS-S-Pae, ASP), two hybrid materials that can self-assemble in water to form hybrid nanoparticles (HP-NPs) co-loaded with paclitaxel and baicalin (HP-NPs@PTX/Bai). The experimental results show that our designed hybrid nanoparticles can be specifically released in the tumour microenvironment and deliver the antitumor drug PTX as well as Bai, which reshapes the phenotype of TAMs, to the tumour site. The hybrid nanoparticles not only effectively re-educated TAMs from M2 TAM to M1 TAM, but also ameliorated the cytotoxic side effects caused by free PTX and provided better tumour suppression than free PTX and HP.

Multiple stimuli-responsive nanosystem for potent, ROS-amplifying, chemo-sonodynamic antitumor therapy

Although sonodynamic therapy (SDT) is a promising non-invasive tumor treatment strategy due to its safety, tissue penetration depth and low cost, the hypoxic tumor microenvironment limits its therapeutic effects. Herein, we have designed and developed an oxygen-independent, ROS-amplifying chemo-sonodynamic antitumor therapy based on novel pH/GSH/ROS triple-responsive PEG-PPMDT nanoparticles. The formulated artemether (ART)/Fe3O4-loaded PEG-PPMDT NPs can rapidly release drug under the synergistic effect of acidic endoplasmic pH and high intracellular GSH/ROS levels to inhibit cancer cell growth. Besides, the ROS level in the NPs-treated tumor cells is magnified by ART via interactions with both Fe2+ ions formed in situ at acidic pH and external ultrasound irradiation, which is not affected by hypoxia tumor microenvironment. Consequently, the enriched intracellular ROS level can cause direct necrosis of ROS-stressed tumor cells and further accelerate the drug release from the ROS-responsive PEG-PPMDT NPs, achieving an incredible antitumor potency. Specifically, upon the chemo-sonodynamic therapy by ART/Fe3O4-loaded PEG-PPMDT NPs, all xenotransplants of human hepatocellular carcinoma (HepG2) in nude mice shrank significantly, and 40% of the tumors were completely eliminated. Importantly, the Fe3O4 encapsulated in the NPs is an efficient MRI contrast agent and can be used to guide the therapeutic procedures. Further, biosafety analyses show that the PEG-PPMDT NPs possess minimal toxicity to main organs. Thus, our combined chemo-sonodynamic therapeutic method is promising for potent antitumor treatment by controlled release of drug and facile exogenous generation of abundant ROS at target tumor sites.

Interventional magnetic-resonance-guided cryotherapy combined with microsurgery for recurrent glioblastoma: An innovative treatment?

BackgroundGlioblastoma invariably recurs after primary Stupp tumor therapy and portends a poor prognosis. Cryoablation is a well-established treatment strategy for extra-cranial tumors. The safety and efficacy of interventional MR-guided cryoablation (iMRgC) has not been explored in recurrent glioblastoma. MethodsA retrospective analysis of data collected over a period of 24 months was performed. The inclusion criteria were: (I) recurrent glioblastoma despite Stupp protocol; (II) MRI followed by histological confirmation of recurrent glioblastoma; (III) location allowing iMRgC followed by microsurgical resection; and (IV) patient's consent. The primary objective was to assess feasibility in terms of complications. The secondary objective was to analyze progression-free survival (PFS), post-iMRgC survival and overall survival (OS). ResultsThe study included 6 patients, with a mean age of 67±7.6 years [range, 54–70 years]. No major complications were observed. Median PFS was 7.5 months [IQR 3.75–9.75] and 6-month PFS was 50%. Median post-iMRgC survival was 9 months [IQR 7.5–15.25] and 6-month post-iMRgC survival was 80%. Median OS was 22.5 months [IQR 21.75–30]. ConclusioniMRgC for recurrent glioblastoma demonstrated a good safety profile, with no major complications. Our data suggest improved PFS and OS. Trial registration numberNo. IRB00011687 retrospectively registred on July 7th 2021.

The Role of the Tumor Microenvironment and Treatment Strategies in Colorectal Cancer

Colorectal cancer (CRC) has the second highest mortality rate among all cancers worldwide. Surgery, chemotherapy, radiotherapy, molecular targeting and other treatment methods have significantly prolonged the survival of patients with CRC. Recently, the emergence of tumor immunotherapy represented by immune checkpoint inhibitors (ICIs) has brought new immunotherapy options for the treatment of advanced CRC. As the efficacy of ICIs is closely related to the tumor immune microenvironment (TME), it is necessary to clarify the relationship between the immune microenvironment of CRC and the efficacy of immunotherapy to ensure that the appropriate drugs are selected. We herein review the latest research progress in the immune microenvironment and strategies related to immunotherapy for CRC. We hope that this review helps in the selection of appropriate treatment strategies for CRC patients.

Engineering NK-92 Cell by Upregulating CXCR2 and IL-2 Via CRISPR-Cas9 Improves Its Antitumor Effects as Cellular Immunotherapy for Human Colon Cancer.

Natural killer (NK) cells have shown good application prospects in adoptive cellular immunotherapy against cancer. However, due to its insufficient infiltration and low activity, the therapeutic effect of infused NK cells has been limited in solid tumors, such as colorectal cancer. It has been proved that tumor-produced chemokines regulate the migration of NK cells expressing corresponding chemokine receptors, and cytokines could enhance the antitumor activity of NK cells. In this study, we innovatively upregulated the expression of chemokine receptor CXC chemokine receptor 2 (CXCR2) and cytokine interleukin (IL)-2 on NK-92 cells using CRISPR-Cas9 gene-editing technology. We demonstrated that overexpressing CXCR2 and IL-2 promotes NK-92 cells to increasingly transfer into tumor sites and achieve stronger cell-killing and proliferation activity. Moreover, the inhibitory effects of gene-edited NK-92 cells on the growth of human colon cancer in vivo were also improved. The tumor burden of tumor-bearing mice was reduced, and their survival time was significantly prolonged. Gene-editing modification NK cells are expected to become a novel and promising tumor treatment strategy.

Polyamine-activated carbonyl stress strategy for oxidative damage therapy

Oxidative damage, which mainly includes cell membrane lipid peroxidation (LPO) and DNA damage, plays a vital role in tumor therapy. Unfortunately, the overproduction of polyamines in tumor tissues inhibits cell membrane LPO and promotes DNA repair, leading to the limited oxidative damage efficacy. Herein, we propose an innovative polyamine-activated carbonyl stress strategy based on the MIL-100 @PAO@PVP (MPP) nanoplatform that successfully overcomes the drawbacks of oxidative damage therapy and achieves excellent chemodynamic therapy (CDT)-induced oxidative damage efficacy. Once endocytozed by tumor cells, the loaded plasma amine oxidase (PAO) on MPP can rapidly deplete polyamines at the tumor site to produce a large amount of highly toxic acrolein and H2O2. The produced H2O2 enhances the MIL-100-driven CDT efficiency to promote cell membrane and DNA damage. Furthermore, the depletion of polyamines further reduces the stability of the cell membrane and DNA. More importantly, the reactive product, acrolein, induces carbonyl stress to further increase DNA damage, inhibit the expression of GPx4 and DNA repair proteins, and significantly enhance CDT-induced oxidative damage. Overall, this strategy not only efficiently overcomes the drawbacks of oxidative damage but also provides a new strategy for tumor treatment.

Transcutaneous tumor vaccination combined with anti-programmed death-1 monoclonal antibody treatment produces a synergistic antitumor effect

Transcutaneous immunization (TCI) has the advantages of safety, high efficiency, non-invasiveness and convenient use. The key for a TCI system is transdermal targeted delivery of antigen to dendritic cells (DCs), the most powerful antigen presenting cells. DCs also play an important role in tumor immunotherapy, which provides a huge imagination for the application of TCI to tumor treatment. In this study, a transcutaneous tumor vaccine (TTV) delivery system was developed using the electrospun silk fibroin (SF) and polyvinyl alcohol (PVA) composite nanofibrous patch loaded with mannosylated polyethyleneimine (PEIman)-modified ethosome (Eth) (termed Eth-PEIman). Eth-PEIman showed a good performance in targeting DCs, and the carriers loaded with antigen (encapsulated in Eths) and adjuvant (absorbed in PEIman) were observed effectively induce DCs maturation in vitro. With the tyrosinase-related protein-2 (TRP2) peptide as antigen and oligodeoxynucleotides containing unmethylated CpG motifs as adjuvant, the TTV-loaded patches (TTVP) significantly inhibited the growth of melanoma in a syngeneic mouse model for melanoma by subcutaneous injection of B16F10 cell lines. Moreover, the combined application of the TTVP and anti-programmed death-1 monoclonal antibody (aPD-1) produced a synergistic antitumor effect, which could be related to the infiltration of more CD4+ and CD8+ T cells in the tumor tissues. The application of TTVP also increased the expression of IL-12, which may be part of the mechanism of synergistic antitumor effect between the TTVP and aPD-1. These results suggest that the combination of the TTVP and immune checkpoint blockers could be an effective strategy for tumor treatment. Statement of significanceTranscutaneous immunization has the advantages of safety, high efficiency, non-invasiveness and convenient use. In this study, a novel transcutaneous tumor vaccine patch (TTVP) was developed using tumor antigens-loaded ethosomes that can target dendritic cells percutaneously. Our data demonstrated that the TTVP can significantly inhibit tumor growth. Furthermore, the combination of TTVP and aPD-1 produced a synergistic anti-melanoma effect. Considering its convenience and non-invasiveness, this TTVP system could find good application prospects in immunotherapy. The combination of TTVP and aPD-1 could be a useful strategy for the prevention and treatment of tumors.

An aggregation-induced emission fluorescence probe for evaluating the effect of CYP450 changes under tumor chemotherapy

Cancer is a complex disease with very high incidence and mortality rates every year. However, cancer drug resistance greatly mitigates the cure rates of tumors, and cytochrome P450 (CYP450) plays an important role in the development of cisplatin resistance. We developed the aggregation-induced emission luminogen (AIEgen) TPE-CYP to monitor the changes in CYP450. The TPE-CYP fluorescent probe was successfully used to assess CYP450 levels in tumor cells and tumor tissue sections. This study presented that CYP450 level in HepG2/DDP cells (cisplatin-resistant cells) was higher than that in HepG2 cells, and the inhibition of CYP450 by 1-ABT effectively improved the tumor resistance. Thus, CYP450 plays a key role in the development of tumor resistance. The synergistic effect of 1-ABT and the chemotherapeutic agent cisplatin was superior to that of cisplatin alone in tumor-bearing mice. The TPE-CYP probe will provide an idea for the clinical implementation of individualized tumor treatment strategies, through the accurate monitoring of CYP450.

Mitochondrial complex I inhibitors suppress tumor growth through concomitant acidification of the intra- and extracellular environment

The disruption of the tumor microenvironment (TME) is a promising anti-cancer strategy, but its effective targeting for solid tumors remains unknown. Here, we investigated the anti-cancer activity of the mitochondrial complex I inhibitor intervenolin (ITV), which modulates the TME independent of energy depletion. By modulating lactate metabolism, ITV induced the concomitant acidification of the intra- and extracellular environment, which synergistically suppressed S6K1 activity in cancer cells through protein phosphatase-2A-mediated dephosphorylation via G-protein-coupled receptor(s). Other complex I inhibitors including metformin and rotenone were also found to exert the same effect through an energy depletion-independent manner as ITV. In mouse and patient-derived xenograft models, ITV was found to suppress tumor growth and its mode of action was further confirmed. The TME is usually acidic owing to glycolytic cancer cell metabolism, and this condition is more susceptible to complex I inhibitors. Thus, we have demonstrated a potential treatment strategy for solid tumors.