Antitumor Therapy Research Articles

Tissue-resident memory CD103+CD8+ T cells in colorectal cancer: its implication as a prognostic and predictive liver metastasis biomarker

BackgroundTissue-resident memory CD103+CD8+ T cells (CD103+CD8+ TRMs) are important components of anti-tumor immunity. However, the significance of CD103+CD8+ TRMs in colorectal cancer (CRC) and their advantages remain unclear.MethodsClinical data and specimens were used to evaluate the significance of CD103+CD8+ TRMs in CRC. A mouse subcutaneous tumorigenesis model and colony-formation assay were conducted to evaluate the anti-tumor effects of CD103+CD8+ TRMs. Finally, the infiltration density and function of CD103+CD8+ TRMs in the tumors were evaluated using flow cytometry.ResultsIn this study, we showed that highly infiltrated CD103+CD8+ TRMs were associated with earlier clinical stage and negative VEGF expression in CRC patients and predicted a favorable prognosis for CRC/CRC liver metastases patients. Interestingly, we also found that CD103+CD8+ TRMs may have predictive potential for whether CRC develops liver metastasis in CRC. In addition, we found a positive correlation between the ratio of the number of α-SMA+ vessels to the sum of the number of α-SMA+ and CD31+ vessels in CRC, and the infiltration level of CD103+CD8+ TRMs. In addition, anti-angiogenic therapy promoted infiltration of CD103+CD8+ TRMs and enhanced their ability to secrete interferon (IFN)-γ, thus further improving the anti-tumor effect. Moreover, in vivo experiments showed that compared with peripheral blood CD8+ T cells, CD103+CD8+ TRMs infused back into the body could also further promote CD8+ T cells to infiltrate the tumor, and they had a stronger ability to secrete IFN-γ, which resulted in better anti-tumor effects.ConclusionWe demonstrated that CD103+CD8+ TRMs have the potential for clinical applications and provide new ideas for combined anti-tumor therapeutic strategies, such as anti-tumor angiogenesis therapy and CAR-T combined immunotherapy.

High-Lactate-Metabolizing Photosynthetic Bacteria Reprogram Tumor Immune Microenvironment.

The elevated levels of lactate in tumor tissue play a pivotal role in fostering an immunosuppressive microenvironment. Therefore, efficiently reducing lactate levels to reprogram tumor immune microenvironment (TIM) is considered a crucial step for boosted immunotherapy. Here, a high-lactate-metabolizing photosynthetic bacteria (LAB-1) is selectively screened for TIM reprogramming, which then improves the efficacy of tumor immunotherapy. The culture medium for LAB-1 screening is initially developed through an orthogonal experiment, simulating the tumor microenvironment (TME) and utilizing lactate as the sole organic carbon source. As demonstrated in a murine 4T1 model, LAB-1 colonizes the TME selectively, resulting in a significant reduction in lactate levels and a subsequent increase in pH values within the tumor tissue. Furthermore, single-cell RNA sequencing analysis reveals that LAB-1 effectively reprograms the TIM, thereby enhancing the effectiveness of antitumor immune therapy. This approach of utilizing lactate-consuming bacteria represents a potent tool for augmenting tumor immunotherapy efficiency.

B-cell performance in chemotherapy: Unravelling the mystery of B-cell therapeutic potential.

The anti-tumour and tumour-promoting roles of B cells in the tumour microenvironment (TME) have gained considerable attention in recent years. As essential orchestrators of humoral immunity, B cells potentially play a crucial role in anti-tumour therapies. Chemotherapy, a mainstay in cancer treatment, influences the proliferation and function of diverse B-cell subsets and their crosstalk with the TME. Modulating B-cell function by targeting B cells or their associated cells may enhance chemotherapy efficacy, presenting a promising avenue for future targeted therapy investigations. This review explores the intricate interplay between chemotherapy and B cells, underscoring the pivotal role of B cells in chemotherapy treatment. We summarise promising B-cell-related therapeutic targets, illustrating the immense potential of B cells in anti-tumour therapy. Our work lays a theoretical foundation for harnessing B cells in chemotherapy and combination strategies for cancer treatment. Chemotherapy can inhibit B-cell proliferation and alter subset distributions and functions, including factor secretion, receptor signalling, and costimulation. Chemotherapy can modulate complex B-cell-T-cell interactions with variable effects on anti-tumour immunity. Targeting B-cell surface markers or signalling improves chemotherapy responses, blocks immune evasion and inhibits tumour growth. Critical knowledge gaps remain regarding B-cell interactions in TME, B-cell chemoresistance mechanisms, TLS biology, heterogeneity, spatial distributions, chemotherapy drug selection and B-cell targets that future studies should address.

Clinical impacts of immunomodulator withdrawal from anti-tumor necrosis factor combination therapy in pediatric inflammatory bowel disease.

Combination therapy consists of both anti-tumor necrosis factor (anti-TNF) and an immunomodulator (IMM) and has been shown to improve outcomes in patients with inflammatory bowel disease (IBD). This study assesses the impacts of IMM withdrawal from combination therapy to anti-TNF monotherapy in children with IBD. This single-center retrospective cohort study included children with IBD initiated on combination therapy between 2014 and 2019 who discontinued the IMM. We evaluated whether IMM withdrawal impacts laboratory values and disease activity. Linear mixed effects models with random intercepts were used to compare differences between groups. Chi-square and Kruskal-Wallis tests were used for comparisons between patients who did and did not require subsequent escalation of therapy. One hundred and fifty-two patients discontinued the IMM which did not significantly affect disease activity. However, 18% of patients escalated therapy after IMM withdrawal, primarily due to low anti-TNF levels. Lower anti-TNF and higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels before IMM withdrawal were associated with subsequent escalation of therapy. Overall, there was no statistically significant effect on anti-TNF drug levels. Patients with Crohn's disease (CD) on infliximab (IFX) and methotrexate (MTX) who discontinued the IMM had an increase in mean ESR and CRP (p < 0.05). IMM withdrawal from anti-TNF combination therapy may be considered safe in the setting of higher anti-TNF levels and normal serum inflammatory markers. Clinicians should consider assessing anti-TNF levels and inflammatory markers after IMM withdrawal, especially in patients with CD receiving IFX who discontinued MTX.

Two-tailed modification module tuned steric-hindrance effect enabling high therapeutic efficacy of paclitaxel prodrug nanoassemblies

Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy, mainly comprise drug modules, response modules and modification modules. However, existing studies usually compare the differences between single types of modification modules, neglecting the impact of steric-hindrance effect caused by chemical structure. Herein, single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs (P-LAC18 and P-BAC18), and the in-depth insights of the steric-hindrance effect on prodrug nanoassemblies were explored. Notably, the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance. Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents, showing faster drug release and stronger antitumor efficacy, but with poorer safety. In contrast, two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics, tumor accumulation and safety due to the good size stability, thus ensuring equivalent antitumor efficacy at tolerance dose. These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structure-activity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.

One-step green synthesis of platinum mesoporous nanoparticles by riboflavin for light activated antitumoral therapy

Photodynamic therapy (PDT) has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments. However, its application has been hindered by the limitations that photosensitizers (PS) have. The combination of PS with metallic nanoparticles like platinum nanoparticles (PtNPs), can help to overcome these intrinsic drawbacks. In this work, the combination of PtNPs and the natural photosensitizer riboflavin (RF) is proposed. PtNPs are synthesized using RF (Pt@RF) as reducing and stabilizing agent in a one-step method, obtaining nanoparticles with mesoporous structure for UV triggered PDT. In view of possible future UV irradiation treatments, the degradation products of RF, ribitol (RB) and lumichrome (LC), this last being a photosensitizing byproduct, are also employed for the synthesis of porous PtNPs, obtaining Pt@LC and Pt@RB. When administered in vitro to lung cancer cells, all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels. The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation. This antitumoral activity is caused by the induction of oxidative stress, shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.

Fe3O4 Nanoparticles That Modulate the Polarisation of Tumor-Associated Macrophages Synergize with Photothermal Therapy and Immunotherapy (PD-1/PD-L1 Inhibitors) to Enhance Anti-Tumor Therapy.

Traditional surgical resection, radiotherapy, and chemotherapy have been the treatment options for patients with head and neck squamous cell carcinoma (HNSCC) over the past few decades. Nevertheless, the five-year survival rate for patients has remained essentially unchanged, and research into treatments has been relatively stagnant. The combined application of photothermal therapy (PTT) and immunotherapy for treating HNSCC has considerable potential. Live-dead cell staining and CCK-8 assays proved that Fe3O4 nanoparticles are biocompatible in vitro. In vitro, cellular experiments utilized flow cytometry and immunofluorescence staining to verify the effect of Fe3O4 nanoparticles on the polarisation of tumor-associated macrophages. In vivo, animal experiments were conducted to assess the inhibitory effect of Fe3O4 nanoparticles on tumor proliferation under the photothermal effect in conjunction with BMS-1. Tumour tissue sections were stained to observe the effects of apoptosis and the inhibition of tumor cell proliferation. The histological damage to animal organs was analyzed by hematoxylin and eosin (H&E) staining. The stable photothermal properties of Fe3O4 nanoparticles were validated by in vitro cellular and in vivo animal experiments. Fe3O4 photothermal action not only directly triggered immunogenic cell death (ICD) and enhanced the immunogenicity of the tumor microenvironment but also regulated the expression of tumor-associated macrophages (TAMs), up-regulating CD86 and down-regulating CD206 to inhibit tumor growth. The PD-1/PD-L1 inhibitor promoted tumor suppression, and reduced tumor recurrence and metastasis. In vivo studies demonstrated that the photothermal action exhibited a synergistic effect when combined with immunotherapy, resulting in significant suppression of primary tumors and an extension of survival. In this study, we applied Fe3O4 photothermolysis in a biomedical context, combining photothermolysis with immunotherapy, exploring a novel pathway for treating HNSCC and providing a new strategy for effectively treating HNSCC.

An injectable composite hydrogel containing polydopamine-coated curcumin nanoparticles and indoximod for the enhanced combinational chemo-photothermal-immunotherapy of breast tumors

The complexity and compensatory evolution of tumors weaken the effectiveness of single antitumor therapies. Therefore, multimodal combination therapies hold great promise in defeating tumors. Herein, we constructed a multi-level regulatory co-delivery system based on chemotherapy, phototherapy, and immunotherapy. Briefly, curcumin (Cur) was prepared as nanoparticles and coated with polydopamine (PDA) to form PCur-NPs, which along with an immune checkpoint inhibitor (indoximod, IND) were then loaded into a thermosensitive Pluronic F127 (F127) hydrogel to form a multifunctional nanocomposite hydrogel (PCur/IND@Gel). The in situ-formed hydrogel exhibited excellent photothermal conversion efficiency and sustained drug release behavior both in vitro and in vivo. In addition, PCur-NPs showed enhanced cellular uptake and cytotoxicity under NIR laser irradiation and induced potent immunogenic cell death (ICD). After intratumoral injection of PCur/IND@Gel, significant apoptosis in 4T1 tumors was induced, dendritic cells in lymph nodes were highly activated, potent CD8+ and CD4+ antitumor immune responses were elicited and regulative T cells in tumors were significantly reduced, which notably inhibited the tumor growth and prolonged the survive time of 4T1 tumor-bearing mice. Therefore, this injectable nanocomposite hydrogel is a promising drug co-delivery platform for chemo-photothermal-immunotherapy of breast tumors.

КОРОНАВИРУСНАЯ ИНФЕКЦИЯ COVID-19 У ПАЦИЕНТОВ С ОСТРЫМ МИЕЛОИДНЫМ ЛЕЙКОЗОМ СТАРШЕЙ ВОЗРАСТНОЙ ГРУППЫ: ОБЗОР ЛИТЕРАТУРЫ И СОБСТВЕННЫЙ ОПЫТ

The presented literature review presents studies, including our own, on the characteristics of the course of coronavirus infection in patients with acute myeloid leukemia in the older age group. Patients with acute leukemia, myelodysplastic syndrome are often over 65 years of age and have a burdened comorbid background and have profound immunodeficiency due to the underlying disease and the antitumor treatment received, and delaying treatment is often impossible due to the urgent need to start antitumor therapy. Management of this cohort of patients with concomitant COVID-19 is a challenge for hematologists around the world and requires interdisciplinary collaboration between hematologists and infectious disease specialists, clinical pharmacologists. There is a need to develop criteria to determine clear indications for starting antitumor treatment against the background of COVID-19 and the optimal timing for resuming the next course of chemotherapy after a coronavirus infection. The analysis of the literature and our own experience showed high hospital mortality taking into account the state of deep immunodeficiency of patients, despite the treatment of COVID-19, secondary bacterial and fungal infections and demonstrated the need to develop, first of all, preventive strategies in elderly patients with acute leukemia.

CURRENT DRUG THERAPY OPTIONS FOR DISSEMINATED HER2-POSITIVE BREAST CANCER AT THE KAZAKH SCIENTIFIC RESEARCH INSTITUTE OF ONCOLOGY AND RADIOLOGY: A CLINICAL CASE

Relevance: Distant outcomes of treatment for Her2neu-positive metastatic breast cancer are improving due to access to innovative drug therapies. The study aimed to demonstrate the initial experience of treating a patient with progressive disseminated hormone receptor-positive breast cancer expressing HER2 (3+) and nearly exhausted options for anti-tumor drug therapy using trastuzumab deruxtecan. Methods: The paper describes a clinical case of a female patient born in 1977 who was diagnosed with Stage IV breast cancer (T1N1M1), invasive ductal carcinoma, and treated at the Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan). Immunohistochemical luminal subtype “B” with Her2neu (3+) expression. Metastatic involvement of skeletal bones with pain syndrome, lungs, liver, axillary, parasternal, and para-mediastinal lymph nodes. Since June 2023, monoclonal antibody conjugate trastuzumab deruxtecan therapy was initiated. The efficacy of fifth-line therapy was assessed using RECIST 1.1 before and during treatment. According to RECIST 1.1., target lesions included a conglomerate of hyperplastic axillary lymph nodes on the right, measuring 1.6 cm, parasternal lymph node 1.6 cm, a lesion in the parenchyma of the lower lobe of the left lung 1.3 cm, lesions (n=2) in the parenchyma of segment 2 of the left liver lobe 1.8 cm and 3.6 cm. Non-target lesion: hyperplastic para-mediastinal lymph nodes SLD 9.9 cm. Results: Pain syndrome was completely relieved after treatment. According to RECIST 1.1. in April 2024, after 11 courses of therapy, target lesions showed size reduction: conglomerate of hyperplastic axillary lymph nodes on the right decreased to 1.0 cm, lesion in the parenchyma of the lower lobe of the left lung increased to 2.7 cm, parasternal lymph node was not visualized, lesions (n=2) in the parenchyma of segment 2 of the left liver lobe measured 1.6 cm and 2.7 cm. Non-target lesion: hyperplastic para-mediastinal lymph nodes were not visualized. Conclusion: According to the clinical study data (DESTINY-Breast02), applying antibody-drug conjugate (ADC) demonstrates better objective response and progression-free survival time in patients previously treated with trastuzumab and taxanes.

Modern approaches in suicidal gene therapy of malignant neoplasms

One of the promising directions in antitumor therapy is suicidal gene therapy based on the introduction of cytotoxic genes into tumor cells. Most often, these genes encode for enzymes of bacterial or viral origin, capable of direct or indirect killing of tumor cells. This review provides information about modern strategies for suicidal cancer gene therapy, discusses their advantages and disadvantages, and analyzes the properties of a potential candidate for creating a new highly effective suicidal system, combining the advantages of existing approaches.

Prognostic analysis of systemic antitumor therapy in young patients with advanced liver cancer: A cohort study.

Advanced liver cancer is the most common malignant tumor in the elderly, but it also occurs in young people in areas where hepatitis B virus is prevalent. The aim of the present study was to assess the efficacy of systemic antitumor therapy in young patients with advanced liver cancer and investigate the influencing factors. The baseline demographic and clinical data of 38 young patients (≤35 years old) with liver cancer were collected as group A and that of 79 elderly patients (≥55 years old) with liver cancer were collected as group B. There were no significant between-group differences regarding the proportion of patients with increased serum aspartate aminotransferase, low serum albumin, increased α-fetoprotein (AFP) and high Child-Pugh score. The median (m)PFS time in groups A and B was 3.9 and 8.3 months, respectively [hazard ratio (HR), 1.702; P=0.009]. The mOS in group A (17.6 months) was 12.4 months shorter than that in group B (HR, 1.799; P=0.010). In the subgroup analysis, male sex [HR, 1.73; 95% confidence interval (CI), 1.07-2.79], pathological diagnosis (HR, 1.79; 95% CI, 1.10-2.91), previous surgical treatment (HR, 2.16; 95% CI, 1.18-3.95), no tumor thrombus (HR, 2.45; 95% CI, 1.22-4.93), increased alanine aminotransferase (HR, 2.23; 95% CI, 1.07-4.65), increased aspartate aminotransferase (HR, 3.22; 95% CI, 1.62-6.39), normal total bilirubin (HR, 1.77; 95% CI, 1.09-2.87) and increased AFP (HR, 2.02; 95% CI, 1.19-3.41) were associated with shorter survival time in group A compared with those in group B (P<0.05). Group A also had a higher incidence of hyper-progressive disease (HPD) (31.6 vs. 3.8%; P<0.001). HPD was a risk factor for advanced liver cancer (HR, 4.530; 95% CI, 2.251-9.115; P<0.001]. In conclusion, the efficacy of systemic antitumor therapy in young patients was poorer compared with that in elderly patients. Young patients with liver cancer had a high HBV infection rate and were prone to HPD.

Nordihydroguaiaretic Acid-Cross-Linked Phenylboronic Acid-Functionalized Polyplex Micelles for Anti-angiogenic Gene Therapy of Orthotopic and Metastatic Tumors.

Polyplexes are required to be equipped with multiple functionalities to accomplish adequate structure stability and gene transfection efficacy for gene therapy. Herein, a 4-carboxy-3-fluorophenylboronic acid (FPBA)-functionalized block copolymer of PEG-b-PAsp(DET/FBA) and PAsp(DET/FBA) (abbreviated as PB and HB) was synthesized and applied for engineering functional polyplex micelles (PMs) through ionic complexation with pDNA followed by strategic cross-linking with nordihydroguaiaretic acid (NDGA) in respect to the potential linkage of polyphenol and FPBA moieties. In relation to polyplex micelles void of cross-linking, the engineered multifunctional polyplex micelles (PBHBN-PMs) were determined to possess improved structural tolerability against the exchange reaction with charged species. Besides, the FPBA/NDGA cross-linking appeared to be selectively cleaved in the acidic endosomal compartments but not the neutral milieu. Furthermore, the PBHB-PMs with the optimal FPBA/NDGA cross-linking degree were identified to possess appreciable cellular uptake and endosomal escape activities, eliciting a significantly high level of gene expression relative to P-PMs and PB-PMs. Eventually, in vivo antitumor therapy by our proposed multifunctional PMs appeared to be capable of facilitating expression of the antiangiogenic genomic payloads (sFlt-1 pDNA) via systemic administration. The enriched antiangiogenic sFlt-1 in the tumors could silence the activities of angiogenic cytokines for the inhibited neo-vasculature and the suppressed growth of orthotopic 4T1 tumors. Of note, the persistent expression of the antiangiogenic sFlt-1 is also presumed to migrate into the blood circulation, thereby accounting for an overall antiangiogenic environment in preventing the potential pulmonary metastasis. Hence, our elaborated multifaceted PMs inspired fascinating potential as an intriguing gene delivery system for the treatment of clinical solid tumors and metastasis.

Recent Advances in Nanoimmunotherapy by Modulating Tumor-Associated Macrophages for Cancer Therapy.

Cancer immunotherapy has yielded remarkable results across a variety of tumor types. Nevertheless, the complex and immunosuppressive microenvironment within solid tumors poses significant challenges to established therapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell (CAR-T) therapy. Within the milieu, tumor-associated macrophages (TAMs) play a significant role by directly suppressing T-cell functionality and fostering an immunosuppressive environment. Effective regulation of TAMs is, therefore, crucial to enhancing the efficacy of immunotherapies. Various therapeutic strategies targeting TAM modulation have emerged, including blocking TAM recruitment, direct elimination, promoting repolarization toward the M1 phenotype, and enhancing phagocytic capacity against tumor cells. The recently introduced CAR macrophage (CAR-M) therapy opens new possibilities for macrophage-based immunotherapy. Compared with CAR-T, CAR-M may demonstrate superior targeting and infiltration capabilities toward solid tumors. This review predominantly delves into the origin and development process of TAMs, their role in promoting tumor growth, and provides a comprehensive overview of immunotherapies targeting TAMs. It underscores the significance of regulating TAMs in bolstering antitumor therapies while discussing the potential and challenges of developing TAMs as targets for immunotherapy.

Anti-tumor therapy through high ROS performance induced by Ag nanoenzyme from boron cluster with halloysite clay nanotubes

The conventional silver nanoparticles (Ag NPs) are characterized with high loading rate and stacking phenomenon, leading to shedding caused biotoxicity and low catalytic efficiency. This seriously hinders their application in biomedicine. Here, we modified the highly dispersible Ag NPs and Ag single-atoms (SAs) synthesis by combining the halloysite clay nanotubes (HNTs) and dodecahydro-dodecaborate (closo-[B12H12]2–) to increase the biocompatible properties and decrease the loading rate. This novel Ag single-atom nanoenzyme alongside Ag NPs nanoenzyme avoid the elevated-temperature calcination while maintaining the exceptionally high-level efficiency of Ag utilization via the reducibility and coordination stabilization of closo-[B12H12]2− and HNTs. With theoretical calculation and electron paramagnetic resonance, we confirmed that both Ag SAzymes and Ag NPs in HNT@B12H12@Ag nanoenzyme are capable decompose the H2O2 into hydroxyl radical (·OH). For the application, we investigated the catalytic activity in the tumor cells and antitumor effects of HNT@B12H12@Ag nanoenzyme both in vitro and in vivo, and confirmed that it effectively suppressed melanoma growth through ·OH generation, with limited biotoxicity. This study provides a novel Ag nanoenzyme synthesis approach to increase the possibility of its clinical application.

Environmentally responsive hydrogel promotes vascular normalization to enhance STING anti-tumor immunity

The immunosuppressive microenvironment of malignant tumors severely hampers the effectiveness of anti-tumor therapy. Moreover, abnormal tumor vasculature interacts with immune cells, forming a vicious cycle that further interferes with anti-tumor immunity and promotes tumor progression. Our pre-basic found excellent anti-tumor effects of c-di-AMP and RRx-001, respectively, and we further explored whether they could be combined synergistically for anti-tumor immunotherapy. We chose to load these two drugs on PVA-TSPBA hydrogel scaffolds that expressly release drugs within the tumor microenvironment by in situ injection. Studies have shown that c-di-AMP activates the STING pathway, enhances immune cell infiltration, and reverses tumor immunosuppression. Meanwhile, RRx-001 releases nitric oxide, which increases oxidative stress injury in tumor cells and promotes apoptosis. Moreover, the combination of the two presented more powerful pro-vascular normalization and reversed tumor immunosuppression than the drug alone. This study demonstrates a new design option for anti-tumor combination therapy and the potential of tumor environmentally responsive hydrogel scaffolds in combination with anti-tumor immunotherapy.

The prognostic impact of severe grade immune checkpoint inhibitor related pneumonitis in non-small cell lung cancer patients.

To compare the prognostic differences between non-small cell lung cancer (NSCLC) patients with mild and severe checkpoint inhibitor-associated pneumonitis (CIP), and explore the causes of death and prognostic risk factors in NSCLC patients with severe CIP. A retrospective study of a cohort of 116 patients with unresectable stage III or IV NSCLC with any grade CIP from April 2016 to August 2022 were conducted. To analyze the clinical characteristics of patients with different CIP grades, patients were divided into mild CIP group (grade 1-2, n=49) and severe CIP group (grade 3-5, n=67) according to the grade of CIP. To explore the OS-related risk factors in the severe CIP group, the patients were divided into a good prognosis (GP) group (≥ median OS, n=30) and a poor prognosis (PP) group (< median OS, n=37) based on whether their overall survival (OS) were greater than median OS. Baseline clinical and laboratory data were collected for analysis. The median OS of all NSCLC patients combined with CIP was 11.4 months (95%CI, 8.070-16.100), The median OS for mild CIP and severe CIP was 22.1 months and 4.4 months respectively (HR=3.076, 95%CI, 1.904-4.970, P<0.0001). The results showed that the most common cause of death among severe CIP patients in the PP group was CIP and the most common cause in the GP group was tumor. The univariate regression analysis showed that suspension of antitumor therapy was a risk factor for poor prognosis (OR=3.598, 95%CI, 1.307-9.905, p=0.013). The multivariate logistic regression analysis showed that suspension of anti-tumor therapy (OR=4.24, 95%CI, 1.067-16.915, p=0.040) and elevated KL-6 (OR=1.002, 95%CI, 1.001-1.002, p<0.001) were independent risk factors for poor prognosis. In conclusion, patients with severe CIP had a poor prognosis, especially those with elevated KL-6, and the main cause of death is immune checkpoint inhibitor-associated pneumonitis complicated with infection. In addition, anti-tumor therapy for severe CIP patients should be resumed in time and should not be delayed for too long.

Efficacy of Cisplatin-CXCR4 Antagonist Combination Therapy in Oral Cancer.

Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin-AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC.

Социологическое исследование оценки врачами-онкологами и врачами-радиотерапевтами изменений доступности противоопухолевой терапии при реализации федерального проекта «Борьба с онкологическими заболеваниями».

The federal project «Fight against oncological diseases» is aimed at increasing the availability of cancer care that meets clinical guidelines. The purpose is to study the degree of use of clinical guidelines by oncologists and radiotherapists, the attitude to changes in the payment system for antitumor treatment by diagnosis-related group (DRG) of diseases and the opinion on the availability of antitumor therapy. M a t e r i a l s a n d m e t h o d s . A survey of 436 oncologists and radiotherapists was conducted. Results. Oncologists and radiotherapists actively use clinical guidelines in their practice. The majority of respondents positively assessed the changes in the payment system for antitumor drug therapy for DRG starting in 2018 (the inclusion of specific drug therapy regimens in DRG) and radiation therapy starting in 2019. Oncologists are 2 times more likely to face restrictions on the allocation of volumes of medical care in the «oncology» profile for antitumor drug therapy both in round-the-clock and day hospitals than for surgical treatment and radiation therapy. At the same time, 2/3 of the respondents noted that medical care for patients with solid tumors has become more accessible.

Curcumin Nanoparticles-related Non-invasive Tumor Therapy, and Cardiotoxicity Relieve.

Non-invasive antitumor therapy can treat tumor patients who cannot tolerate surgery or are unsuitable. However, tumor resistance to non-invasive antitumor therapy and cardiotoxicity caused by treatment seriously affect the quality of life and prognosis of patients. As a kind of polyphenol extracted from herbs, curcumin has many pharmacological effects, such as anti-inflammation, antioxidation, antitumor, etc. Curcumin plays the antitumor effect by directly promoting tumor cell death and reducing tumor cells' invasive ability. Curcumin exerts the therapeutic effect mainly by inhibiting the nuclear factor-κB (NF-κB) signal pathway, inhibiting the production of cyclooxygenase-2 (COX-2), promoting the expression of caspase-9, and directly inducing reactive oxygen species (ROS) production in tumor cells. Curcumin nanoparticles can solve curcumin's shortcomings, such as poor water solubility and high metabolic rate, and can be effectively used in antitumor therapy. Curcumin nanoparticles can improve the prognosis and quality of life of tumor patients by using as adjuvants to enhance the sensitivity of tumors to non-invasive therapy and reduce the side effects, especially cardiotoxicity. In this paper, we collect and analyze the literature of relevant databases. It is pointed out that future research on curcumin tends to alleviate the adverse reactions caused by treatment, which is of more significance to tumor patients.