Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.

Endostatin enhances antitumor effect of tumor antigen-pulsed dendritic cell therapy in mouse xenograft model of lung carcinoma

Objective： To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell （DC）-T cell therapy on lung cancer. Methods： Transplanted Lewis lung cancer （LLC） models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC- T＋endostatin group, DC-T group, and phosphate-buffered saline （PBS） control group. Microvessel density （MVD） of tumor tissue in tumor-bearing mice was determined by immunohistochemistry （IHC）. The expressions of vascular endothelial growth factor （VEGF） and hypoxia-inducible factor-1α （HIF-1α） were determined by Western blotting and IHC staining. The proportions of CD8＋ T cells, mature dendritic cells （mDC）, tumor-associated macrophages [TAM （M1/M2）], and myeloid-derived suppressor cells （MDSC） in suspended cells of tumor tissue were determined by flow cytometry. The expressions of inter｜eukin （IL）-6, IL-10, IL-17, transforming growth factor-β（TGF-β） and interferon-γ （IFN-γ） in suspended cells of tumor tissue were detected by enzyme-linked immune sorbent assay （ELISA）. Results： DC-T cells combined with endostatin remarkably suppressed tumor growth. MVD of mice in DC- T＋endostatin group was significantly lower than that of the control group and DC-T monotherapy group. The expressions of VEGF, IL-6 and IL-17 in tumors were markedly decreased, but IFN-γ, and HIF-1α increased after treating with DC-T cells combined with endostatin, compared to control group and DC-T group. In the DC- T＋endostatin group, the proportions of MDSC and TAM （M2 type） were significantly decreased, mDC and TAM （Nil type） were up-regulated, and CD8＋ T cells were recruited to infiltrate tumors, in contrast to PBS control and DC-T monotherapy. DC-T cells combined with endostatin potently reduced the expressions of IL-6, IL-10, TGF-β and IL-17 in tumor tissue, and enhanced the expression of IFN-γ. Conclusions： The study indicated the synergic antitumor effects between endostatin and tumor antigen-pulsed DC-T cells, which may be a prospective therapy strategy to achieve potent antitumor effects on lung cancer.

A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.

miR-30a-5p/PHTF2 axis regulates the tumorigenesis and metastasis of lung adenocarcinoma

Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung adenocarcinoma.Method:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal tissues.Cellular experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma cells.Furthermore,we examined tumorigenesis and metastasis in a nude mouse model.Results:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma samples.Transfection of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant characteristics.Notably,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal model.Moreover,PHTF2 was found to be a molecular target of miR-30a-5p.Upregulating PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p mimic.Conclusion:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung adenocarcinoma.Therefore,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

CA IX-targeted Ag_(2)S quantum dots bioprobe for NIR-II imaging-guided hypoxia tumor chemo-photothermal therapy

Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the tumors.Therefore,the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned.As carbonic anhydrase IX(CA IX)is abundantly distributed on the hypoxia tumor cells,it is considered as a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfonamide(ABS)as a CA IX inhibitor has inherent inhibitory activity and good targeting effect.In this study,Ag_(2)S quantum dots(QDs)were used as the carrier to prepare a novel diagnostic and therapeutic bioprobe(Ag_(2)S@polyethylene glycol(PEG)-ABS)through ligand exchange and amide condensation reaction.Ag_(2)S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor imaging by the near infrared-II(NIR-II)fluorescence characteristics of Ag_(2)S QDs.PEG modification of Ag_(2)S QDs greatly improves its water solubility and stability,and therefore achieves high photothermal stability and high photothermal conversion efficiency(PCE)of 45.17%.Under laser irradiation,Ag_(2)S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in vitro.It also has been proved that Ag_(2)S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility.Therefore,it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

DNA Damage-driven Inflammatory Cytokines:Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy

DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

Progress of Immunotherapy Combined with Anti-Angiogenesis Therapy in Lung Cancer

Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditional chemotherapy modalities, many emerging treatments are increasingly significant, such as immunotherapy, anti-angiogenic therapy, and targeted therapy. An increasing number of studies have now shown that anti-angiogenic therapy improves the immune microenvironment by enhancing tumor immunity through normalization of tumor vessels. Immunization combined with anti-angiogenic therapy can exert synergistic effects and improve the prognosis of patients. This article summarizes the extent of benefit, current clinical study data, and future prospects of immunotherapy combined with anti-angiogenic agents in the treatment of advanced NSCLC.

Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling

It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still unclear.The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)dataset.Frequent HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC.HE4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways.The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects.Moreover,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD.Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.

Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Dosimetric Impact of Tumor Position and Lung Density Variations in Lung Stereotactic Body Radiotherapy

Purpose of this study was to evaluate the variation of the dose to gross tumor volume (GTV) related to tumor position and lung density for lung stereotactic body radiotherapy (SBRT) using a virtual phantom. The density of the equivalent lung surrounding the GTV (10 mm diameter) was defined as 0.10, 0.15, 0.25, 0.35, and 0.45 g/cm3. A planning target volume (PTV) was generated by adding a uniform 8 mm margin to the internal target volume (ITV). We defined that the 99% of the GTV should be covered by 100% of the prescribed dose using Monte Carlo (MC) calculation. The GTV structure was replicated from ITV to the PTV periphery at 1 mm intervals. Planned dose to the GTV was defined as the predicted dose in the replicated GTV structure. Simulated dose to the GTV was defined as the calculated dose in the replicated GTV structure taking into account the tumor position error. D99 of the planned dose to the GTV at the 8 mm shift position was 78.1%, 81.6%, 87.3%, 91.4% and 94.4% at equivalent lung densities of 0.10, 0.15, 0.25, 0.35, and 0.45 g/cm3, respectively. D99 of the simulated dose to the GTV at the 8 mm shift position was 96.9%, 95.3%, 94.2%, 95.1 % and 96.3% at equivalent lung densities of 0.10, 0.15, 0.25, 0.35, and 0.45 g/cm3, respectively. Planned dose to GTV is strongly dependent on lung density and tumor position errors, while simulated dose to GTV does not show any significant dependence.

Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Significance of Multimodality Therapy in Patients with a Superior Sulcus Tumor of the Lung: A Review Article

Despite the aggressive pursuit of diagnostic and treatment modalities for lung cancer, the treatment outcomes are still not satisfactory, and even patients with surgically resectable non-small cell lung cancer (NSCLC) are often at considerable risk of suffering recurrence and/or death from lung cancer. Regarding the treatment of patients with locally advanced, resectable NSCLC, several retrospective and prospective studies have shown the significance of multimodality treatments with preoperative chemoradiotherapy and surgical treatment. However, no definitive treatment strategies for locally advanced NSCLC patients have yet been established. One of the reasons for the lack of established treatment strategies for patients with locally advanced NSCLC is considered to be the heterogeneity of the population, i.e., cT4N0, cT3-4N1 and cT1a-3N2 tumors are included in stage IIIA disease, and superior sulcus tumors (SSTs) are also included in this classification. With regard to SST, two representative prospective phase II trials indicated the efficacy of surgical treatment following concurrent radiation and chemotherapy. In a study conducted by the Southwest Oncology Group, 110 patients with superior sulcus NSCLC were treated with two cycles of cisplatin and etoposide concurrently with 45 gray (Gy) of radiation, followed by surgical treatment and two additional cycles of chemotherapy postoperatively. The response rate (RR) to the preoperative chemoradiotherapy was 86%, and 83 patients (76%) were able to undergo complete resection. A pathological complete response (CR) was observed in 61 patients (56%), and the five-year survival of all patients and those undergoing complete resection was 44% and 54%, respectively. A phase II study conducted by the Japan Clinical Oncology Group examined the safety and efficacy of preoperative concurrent chemoradiotherapy using mitomycin, vinblastin and cisplatin followed by surgical treatment. Seventy-six patients with SST were enrolled in this study, and all received chemotherapy using two cycles of MVP concurrently with 45 Gy of radiation, followed by surgery. Neoadjuvant chemoradiotherapy resulted in a 61% RR, and pathological complete resection was successfully achieved in 51 patients (68%). A pathological CR was observed in 12 patients (16%), and the disease-free and overall survival rates at five years were 45% and 56%, respectively. Both studies showed the efficacy and tolerability of the multimodality treatment for SST, thus suggesting that multimodality treatment with preoperative chemoradiotherapy followed by surgery may therefore be an effective treatment for resectable SST. We herein review the results of retrospective and prospective studies while assessing the treatment outcomes of NSCLC patients with SST.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma

BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.

New method of local adjuvant therapy with bicarbonate Ringer’s solution for tumoral calcinosis: A case report

BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection difficult.An adjuvant method to remove or resolve the residual crystals during the operation is necessary.CASE SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the adjuvant.After resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was observed.Considering the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot lesion.After resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s solution.CONCLUSION The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.

Nanomaterials for refining tumor microenvironment and enhancing therapy in head and neck squamous cell carcinoma: a review

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.

Systemic therapy in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

Effect of Individualized Exercise Therapy on Cancer-related Fatigue and Negative Emotion in Patients with Gastrointestinal Tumor during Perioperative Period

[Objectives]To investigate the effect of exercise therapy in gastric cancer patients during perioperative period.[Methods]100 patients with gastric cancer who underwent elective operation in the Department of Gastrointestinal Surgery of Taihe Hospital Affiliated to Hubei University of Medicine were divided into observation group and control group by convenience sampling.The control group received routine nursing measures,and the experimental group received exercise therapy intervention measures on the basis of the control group.The patients were evaluated by the General Information Questionnaire,Self-Rating Anxiety Scale,Self-Rating Depression Scale and Cancer-related Fatigue Scale at the time of admission,the second week and the sixth week after operation.[Results]The time effect,intervention effect and interaction effect of anxiety score,depression score and cancer-related fatigue score were significant(all P<0.05)and the index of enhanced recovery after surgery was significant(P<0.05)in the two groups at the second and sixth week after operation.[Conclusions]Exercise therapy is beneficial to promoting the enhanced recovery after surgery in advance,reduce cancer-related fatigue,negative emotion and accelerate rehabilitation in patients with gastrointestinal tumors.