Malignant Tumors Research Articles

Current Research Status of Traditional Chinese Medicine in the Treatment of Lung Adenocarcinoma

Pulmonary adenocarcinoma is a common malignant tumor in clinical practice. Traditional Chinese medicine believes that this disease is often caused by deficiency, leading to excess due to deficiency. It belongs to the category of deficiency with excess as the basis, and positive deficiency as the basis. Phlegm turbidity, qi stagnation, blood stasis, and toxin accumulation accumulate in the lungs as the basis. This article provides a review of the research status of traditional Chinese medicine in the treatment of lung adenocarcinoma in recent years, including etiology and pathogenesis, traditional Chinese medicine prescriptions, empirical prescriptions, and new traditional Chinese medicine preparations. The results show that traditional Chinese medicine can enhance the clinical efficacy of radiotherapy, chemotherapy, or targeted drug treatment, reduce various side effects of Western medicine treatment, reduce drug resistance, and significantly improve the quality of life of patients and prolong their survival.

Does amide proton transfer-weighted MRI have diagnostic and differential value in ovarian cystic and predominantly cystic lesion?

This study aims to evaluate the diagnostic value of amide proton transfer-weighted (APTw) imaging in distinguishing cystic or predominantly cystic ovarian lesions. 49 patients underwent APTw imaging at 3T-MR before surgery, with 20 volunteers serving as the control group. Participants were divided into the following groups: solid components of normal ovaries (Group A, n = 29), solid components of malignant lesions (Group B, n = 7), cystic fluid of follicles (Group C, n = 31), cystic fluid of benign lesions (Group D, n = 46), functional cysts (Group d1, n = 8), endometriomas (Group d2, n = 28), cystadenomas (Group d3, n = 10), and cystic fluid of malignant lesions (Group E, n = 12). Independent t-tests or Mann-Whitney U tests and one-way ANOVA were used to compare group differences. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy in distinguishing between different lesions. For solid components, significant differences in MTRasym values were observed between Groups A and B (P < 0.001). For cystic components, significant differences were found between Groups C and D, C and E, d1 and d2, d2 and d3, d1 and d3, C and d2, C and d3, E and d1, and E and d2 (all P < 0.01). ROC analysis of these results showed high AUC values (ranging from 0.813 to 1.0), all P < 0.05. APTw can reveal differences in MTRasym values between normal and diseased ovarian tissues, demonstrating high clinical value in differentiating functional cysts, endometriomas, and cystadenomas, as well as distinguishing benign lesions (functional cysts or endometriomas) from malignant tumors.

Pulsatilla chinensis functions as a novel antihyperlipidemic agent by upregulating LDLR in an ERK-dependent manner

BackgroundPulsatilla chinensis (PC) is a traditional Chinese medicine (TCM) known for its beneficial activities. It has been historically used to treat dysentery, vaginal trichomoniasis, bacterial infections, and malignant tumors. The therapeutic potential of PC in the management of hypercholesterolemia remains largely unexplored.MethodsA high-throughput screening based on high-throughput sequencing was conducted in HepG2 cells to construct gene expression profiles for several hundred TCMs. In vivo evaluation of the efficacy of PC was performed using rats with hypercholesterolemia. Transcriptome analysis was carried out on PC-treated rat livers and HepG2 cells to investigate the mechanism of action of PC in vitro. The findings were further validated using RT-qPCR and western blot techniques.ResultsPC was identified as similar to Rhizoma Coptidis based on signature genes related to metabolism. Administration of PC via gavage in rats with hypercholesterolemia for 11 weeks resulted in substantially reduced serum total cholesterol and low-density lipoprotein (LDL) cholesterol and ameliorated fatty liver. Transcriptome analysis revealed that PC regulated various pathways associated with lipid metabolism. The LDL receptor (LDLR), a key player in cholesterol metabolism, was upregulated by PC both in vivo and in vitro. It was discovered that PC achieved this upregulation by activating extracellular regulated protein kinase (ERK) signaling in HepG2 cells. To uncover the major bioactive components responsible for the anti- hypercholesterolemia effect of PC, two major saponins, named Pulsatilla saponin D (PCD) and PC anemoside B4 (PCB4), were assessed. PCD, but not PCB4, was identified as the active ingredient responsible for the upregulation of LDLR by PC.ConclusionThese findings demonstrated that PC acts as an antihypercholesterolemic agent by upregulating LDLR in an ERK-dependent manner and holds potential in the treatment of hypercholesterolemia.

Difference in fecal and oral microbiota between pancreatic cancer and benign/low-grade malignant tumor patients

BackgroundSignificant gaps exist in understanding the gastrointestinal microbiota in patients with pancreatic cancer (PCA) versus benign or low-grade malignant pancreatic tumors (NPCA). This study aimed to analyze these microbiota characteristics and explore their potential use in distinguishing malignant pancreatic lesions.MethodsBetween September 2020 and May 2024, fecal and oral samples were collected from 121 patients undergoing surgical resection or diagnostic biopsy of pancreatic lesions, including 75 patients with PCA and 46 patients with NPCA, and 16s rRNA sequencing was performed. Random forest models based using fecal and oral microbiota data were developed to diagnose PCA and NPCA, with performance assessed using the leave-one-out cross validation method.ResultsThe Shannon index and PCoA analysis revealed significant differences in oral microbiota composition between PCA and NPCA (p < 0.001 and p = 0.001, respectively). Fecal microbiome richness differed significantly (p = 0.02), though composition similarity was noted (p = 0.238). LEfSe identified 16 and 23 genera with significant differences in fecal and oral microbiomes, respectively. Random forest classifiers based on fecal and oral microbiota achieved areas under the curves (AUCs) of 89.4% and 96.3%, respectively, for distinguishing PCA and NPCA. In the mucinous tumor cohort, oral and fecal microbiome classifiers outperformed CA19-9, yielding AUCs of 83.0% and 85.2%, respectively.ConclusionFecal and oral microbiota compositions were significantly different between PCA and NPCA patients. Random forest classifiers utilizing fecal and oral microbiota data effectively distinguish between benign or low-grade malignant and malignant pancreatic lesions.

Subsequent Thyroid Carcinomas in Children and Adolescents Registered in the German MET Consortium (1997-2023).

Introduction: Among childhood cancer survivors, the cumulative incidence rate of differentiated thyroid carcinomas (DTCs) is estimated to be 8-11%. Although the association of DTC with prior radiotherapy is well-studied, the association with chemotherapy remains less understood. Most studies focused on young adults, leaving a knowledge gap on subsequent DTC occurring in childhood and adolescence. Methods: In this retrospective cohort study, we analyzed DTCs in children and adolescents under 18 years of age who were registered with the national multicenter Malignant Endocrine Tumor studies in Germany (1997-2023). We compared patients with first primary DTC to those with subsequent DTC that developed after a history of childhood cancer or hematopoietic stem cell transplantation (HSCT). In the subsequent DTC subgroup, we compared DTCs following chemotherapy only to those following chemo- and radiotherapy. Results: Of 505 patients with DTCs, 66 (13.1%) (38 male, 28 female) were subsequent DTCs. The median age at subsequent DTC diagnosis was 12.7 years (range, 5.1-17.9), with a median latency of 7.3 years (range, 2.2-15.6) from the first malignancy or HSCT. The 5-year overall survival (OS) and thyroid-related adverse event-free survival (EFS) estimates from the diagnoses of a subsequent DTC were 100.0% and 82.5%, respectively. Prior treatment included chemotherapy in 64 patients, with 18 receiving chemotherapy alone. In all, 46 subsequent DTC patients had a history of external radiotherapy, including 2 treated with radiotherapy only and 14 with total body irradiation. Two patients received 131I-metaiodobenzylguanidine treatment. Subsequent DTCs versus first DTCs were smaller in size but more frequently multifocal. Subsequent DTCs following chemotherapy only, compared with chemo- and radiotherapy, developed after a shorter latency (median 6.2 vs. 7.8 years), and were larger (median 1.86 vs. 1.18 cm). Patients with subsequent DTCs following chemotherapy only were younger at diagnosis (median 11.5 vs. 13.7 years). No differences were observed for OS and EFS. Conclusions: Presenting features of subsequent DTCs differ from primary counterparts, although the prognosis is not significantly different. Subsequent DTCs following chemotherapy only versus chemo- and radiotherapy DTCs were larger and diagnosed in younger patients after a shorter latency. More research is needed to identify risk factors and mechanisms potentially contributing to thyroid tumorigenesis post-chemotherapy.

Current Combinatorial Therapeutic Aspects: The Future Prospect for Glioblastoma Treatment.

There are several types of brain tumors but glioblastoma (GBM) is one of the highly malignant tumors. A primary concern with GBM is that the treatment is inadequate. Even after giving many multi-stacked combinations of therapies to patients, inclusive of chemotherapy, radiation, and surgery, the median survival rate remains poor. Due to its heterogeneous nature, the use of selective therapy for specific targeting of tumor cells is of particular importance. Although many treatment alternatives which include surgery with adjuvant chemotherapy and radiotherapy are available, the prognosis of the disease is very poor. Combination therapy is becoming the foundation of modern antitumor therapy and it is continuously evolving and developing innovative drug regimens as evidenced by ongoing preclinical and clinical trials. In this review, we discuss the current treatment options and emerging therapeutic approaches for the treatment of GBM. The prospects for alternative glioblastoma therapy are also discussed.

MiR-484 as an "OncomiR" in Breast Cancer Promotes Tumorigenesis by Suppressing Apoptosis Genes.

Breast cancer (BC) is one of the most common causes of death among females. Cancer cells escape from apoptosis, causing the cells to proliferate uncontrollably. MicroRNAs (miRNAs) are known to regulate apoptosis in cancer cells. This study aimed to determine the change in miR-484 in different BC cells and its relationship with the apoptosis pathway. In the study, tumor and healthy tissue samples adjacent to the tumor were collected from 42 patients (6 benign, 36 malignant). Tissue samples were classified according to tumor type, tumor histological grade, proliferation index, and molecular subtypes. Gene expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR), and protein levels were determined using the Western Blot method. The results were analyzed using the delta-delta Ct method. Findings showed that miR-484 expression levels were higher in malignant tumors than in benign tumors, and higher in tumor tissues than healthy tissues. Additionally, it was determined that as Ki-67 levels and histological grade and aggressiveness increased, miR-484 expression levels also increased. In tumor tissue compared with healthy adjacent tissue, there was an increase in BCL2 expression and a decrease in Casp3 and Casp9 expression. Therefore, a positive correlation was found between miR-484 expression and BCL2, and a negative correlation was found between CASP3 and CASP9 expression. Our results show that miR-484 may play a roll as an onco-miR in BC. Increased miR-484 and BCL2, and decreased Casp3, in breast tumor tissues suggest that Casp9 expression may increase uncontrolled cell proliferation by suppressing apoptosis in BC cells and may contribute to tumor progression.

A single-center experience of central nervous system tumors in children under three years old

PurposeThis study aims to summarize the characteristics of children under three years old (≤3 years) with central nervous system (CNS) tumors and to investigate the factors that influence their overall survival (OS) time.MethodsWe treated 171 pediatric patients (≤3 years) with CNS tumors at Yuquan Hospital of Tsinghua University from January 2016 to June 2023. Of these, 162 cases were successfully followed up. Kaplan–Meier survival analysis and Cox regression were utilized to evaluate factors potentially influencing OS of malignancies.ResultsThere was a male predominance among the patients. The three most common tumors were embryonal tumors, gliomas, and craniopharyngiomas. Gross total resection (GTR) was achieved in select cases. Patients with high-grade malignancies were advised to undergo chemotherapy and/or radiotherapy after surgery. Optic gliomas and diffuse midline gliomas were partially resected and treated with adjuvant treatments. The median survival time of low-grade malignant tumors was 41.5 months, while that of high-grade malignant tumors was 15 months. Kaplan–Meier survival analysis identified the factors potentially influencing OS of malignancies: extent of resection, CNS WHO grade, grade of malignancies, and Ki-67 labeling index (Ki-67 LI). Subsequent multivariate analysis highlighted the interactive factor (extent of resection × CNS WHO grade) along with Ki-67 LI, as the most significant variables. Factors such as sex, age, tumor location, and onset-to-treatment time appeared not to affect OS.ConclusionsGTR remains the cornerstone of treatment for children (≤3 years) with CNS tumors, except for optic glioma, diffuse midline glioma, and germinoma. The interactive factor (extent of resection × CNS WHO grade) and Ki-67 LI are the most significant factors affecting OS. The implementation of preoperative neoadjuvant chemotherapy and early postoperative chemotherapy may enhance prognosis.

Detection of transmembrane protein 100 in breast cancer: Correlation with malignant progression and chemosensitivity

Objective: With increased incidence, breast cancer has become the most common malignant tumor in women. Transmembrane protein 100 (TMEM100) is a key factor affecting the progression of malignant tumors. The aim of the study is to examine the molecular mechanism of TMEM100 in malignant progression. Material and Methods: TMEM100 expression was analyzed by Western blot, immunohistochemistry, and real-time quantitative polymerase chain reaction. Cell migration and invasiveness after transfection with TMEM100 were investigated by Transwell assay. 5-ethynyl-2-deoxyuridine staining and cell colony-formation assay were utilized to the exploration of cell proliferation. Flow cytometry was adopted to detect whether TMEM100 affected the effect of Docetaxel on cell apoptosis. The effects of TMEM100 on the Ras-extracellular signal-regulated kinase (RAS/ERK) pathway were explored by Western blot assay. Results: Downregulated TMEM100 expression was in breast cancer tissues (P &lt; 0.01). TMEM100 overexpression hindered the invasion (P &lt; 0.01), migration (P &lt; 0.01), and proliferation (P &lt; 0.01) of breast cancer cells. Chemotherapy sensitivity of breast cancer cells to docetaxel was enhanced by TMEM100 (P &lt; 0.01). TMEM100 inhibited Ras expression and ERK1/2 phosphorylation (P &lt; 0.01). Furthermore, ERK agonist TertButylhydroquinone neutralized the effects of TMEM100 (P &lt; 0.01). Conclusion: TMEM100 blocked malignant progression of breast cancer and enhanced docetaxel chemosensitivity by suppressing RAS/ERK pathway. These data manifested that regulation of TMEM100 expression may affect the progression of breast cancer, and its prognostic value and mechanism deserve further investigation.

Development of a thrombin-antithrombin complex detection kit and study in venous thromboembolism complicated by cervical cancer

ObjectiveOur study successfully developed an assay kit for thrombin-antithrombin complex (TAT) and demonstrated the predictive value of plasma TAT concentration in the development of venous thromboembolism (VTE) in patients with cervical cancer.MethodA retrospective analysis was conducted on 177 patients with cervical cancer who received treatment at the Affiliated Hospital of Jiangnan University in Wuxi City from July 1, 2023 to October 1, 2023. This study provides a comprehensive analysis of cervical cancer patients and their VTE risk factors. The patients were divided into two groups: 27 cases with VTE (Thrombosis group) and 150 cases without VTE (Non-thrombotic group). Additionally, the patients were classified into four stages based on tumor stage: 42 cases of stage I, 45 cases of stage II, 62 cases of stage III, and 28 cases of stage IV. The control group consisted of 80 healthy patients undergoing medical check-ups. Thrombin-antithrombin complex (TAT), fibrinolytic enzyme-α2-fibrinolytic inhibitor complex (PIC), thrombomodulin (TM), and tissue-type plasminogen activator inhibitor 1 complex (t-PAIC) were detected using quantitative chemiluminescence immunoassay. The study assessed the variations in thrombotic marker levels among cervical cancer patients of different stages through a receiver operating characteristic (ROC) curve.ResultThe TAT reagent demonstrated a detection limit of 0.048 ng/mL, with a linear R value of 0.9997, indicating high accuracy and precision. The reagent's accelerated stability was also excellent, with deviations of less than 10%. Furthermore, the correlation coefficient of this method with Hyson Mecon was R2 = 0.9683. Notably, in patients with cervical cancer, TAT and PIC levels were found to be elevated compared to those of the healthy population. Cervical cancer patients who developed thrombosis had significantly elevated levels of TAT and fibrinogen degradation products (FDP) compared to those who did not. Furthermore, patients with stage III-IV cervical cancer exhibited higher levels of the six markers than those with stage I-II during staging. Notably, the combination of four or six markers significantly improved the sensitivity and specificity of the diagnosis, as demonstrated by the ROC curves.ConclusionOur developed TAT test kit has excellent performance and low cost, making it a clinically valuable tool for widespread use. Elevated TAT levels have significant predictive value for thrombosis occurrence in cervical cancer patients. The combination of t-PAIC, TM, TAT, PIC, D-dimer(D-D), and FDP markers is superior to using a single marker for diagnosing VTE in patients with malignant tumors. Screening cervical cancer patients for the six markers is essential to aid in active prophylaxis, determine optimal treatment timing, and implement nursing interventions to improve prognosis, reduce venous thrombosis incidence and mortality, and prolong survival time.

Comprehensive analysis of lysine lactylation and its potential biological significance in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is a common histological subtype of malignant renal neoplasm. Protein lysine lactylation (Kla) plays a crucial role in tumor metabolic reprogramming. However, little is known regarding the distribution and potential biological functions of Kla in ccRCC. This study aimed to systematically investigate the role of Kla in ccRCC.MethodsA total of 12 ccRCC samples were collected from 6 patients. Western blotting was performed to determine the trend of Kla-modified proteins in ccRCC. Liquid chromatography–tandem mass spectrometry was used to quantitatively analyze Kla in ccRCC. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) network analyses were conducted to clarify the biological functions and interactional relationships of differentially lactylated proteins (DLPs).ResultsIn total, 239 DLPs, including 441 lactylated sites, were identified by comparing ccRCC tissues with adjacent normal tissues. Kla-related enzymes have a higher affinity for alanine than for other amino acid residues in ccRCC. Subcellular localization analysis revealed that most DLPs were localized in the cytoplasm and mitochondria. GO enrichment analysis showed that most of the DLPs were enriched in metabolism-associated biological processes, including the purine ribonucleotide, monocarboxylic acid, ribonucleoside triphosphate, purine nucleoside triphosphate, and ATP metabolic processes. KEGG analysis indicated that most DLPs were also enriched in metabolism-related pathways, including glycolysis, amino acid (valine, leucine, and isoleucine) degradation, pyruvate metabolism, fatty acid degradation, and the citrate cycle. The top 20 hub proteins were screened from the PPI network based on their degree ranks.ConclusionsThis study revealed the role of Kla in ccRCC, which will extend our understanding of the potential molecular mechanisms underlying ccRCC formation and progression. These key Kla-modified proteins may be promising therapeutic targets for the treatment of ccRCC. However, further molecular experiments are required to validate these findings.

Outcomes of oncologic arthroplasty in children and adolescents with malignant limb tumors: a systematic review

Background. Amputation was historically the primary surgical intervention for children with limb bone sarcomas. However, the development and refinement of chemotherapy and radiotherapy protocols, along with advances in surgical techniques and implants, have significantly altered the treatment landscape for these patients. Currently, limb-sparing oncologic arthroplasty is the preferred surgical approach for treating limb sarcomas in children. The aim of the systematic review is to analyse the outcomes of oncologic arthroplasty in children and adolescents. Methods. A comprehensive literature search was performed in Google Scholar, PubMed, ScienceDirect, and eLIBRARY databases focusing on the keywords “endoprostheses, tumors, children”, from 2000 to 2024. Data collection included patient demographics (number of patients, gender, age), follow-up period, disease diagnosis, tumor location, type of endoprosthesis, complications, functional outcomes based on the Musculoskeletal Tumor Society score (MSTS) in percentage, overall survival rates, and prosthesis survival rates. Results. The review included the data from 30 articles on a total of 792 patients aged 2 to 18 years, with 422 males and 370 females. The average age was 11.4 years, and the average follow-up period was 6.5 years. Osteosarcoma was the most common diagnosis, accounting for 716 (88.8%) cases, followed by Ewing sarcoma with 67 (8.3%) cases. Distal femoral arthroplasties were performed most frequently (573 cases, 71.1%), followed by proximal tibial arthroplasty (148 cases, 18.3%). The most commonly used type of endoprosthesis was the non-invasively extendable type (540 cases, 67%). A total of 756 complications were recorded, resulting in a complication rate of 96%. The complications were predominantly oncologic (188 cases, 25%) and pediatric orthopedic (166 cases, 22%). The 5-year and 10-year overall survival rates were 81.68% and 77.63%, respectively, with an average prosthesis survival rate of 53.93%. Conclusion. The data obtained indicate an extremely high frequency of complications during oncologic arthroplasty in children, mainly of an orthopedic profile, which requires analysis and development of measures to prevent them, as well as organizational solutions for the correction of these disorders.

Protective effects of miR-24-2-5p in early stages of breast cancer bone metastasis

BackgroundBone is the most frequent site of metastasis for breast cancer (BC). Metastatic BC cells interact with bone cells, including osteoclasts and osteoblasts, creating a cancer niche where they seed and proliferate. MicroRNAs (miRNAs) are regulators of breast-to-bone metastasis progression. MiR-24-2-5p has previously been shown to have roles in both breast cancer progression and inhibition of osteogenic differentiation. However, a direct link between miR-24-2-5p activity and the onset of bone metastasis remains ill-defined.MethodsAnalysis of the expression of miR-24 forms (miR-24-2-5p, miR-24-3p, miR-24-1-5p) in the serum from early-stage BC patients at baseline (time of surgery) was conducted. MiR-24-2-5p overexpression in BC cells (NW1, a luc2-positive subpopulation of MDA-MB-231, and MCF7) was obtained by miRNA mimic transfection or lentivirus transduction. MiR-24-2-5p downregulation in BC cells (ZR-75-1, T-47D, SK-BR-3) was obtained by miRNA inhibitor transfection. Cell proliferation, migration and/or invasion assays were performed to assess BC cell functions after modulation of miR-24-2-5p expression. An animal model was used to assess the effect of miR-24-2-5p overexpression on early BC metastasis formation, as judged by bioluminescence imaging, and on bone remodelling, following measurement of circulating bone resorption (CTX-I) and bone formation (P1NP) markers. The effect of conditioned medium from miR-24-2-5p-overexpressing BC cells on human and murine osteoclast differentiation was investigated. Endogenous miR-24-2-5p expression levels were also quantified during murine osteoclast differentiation. RNA-sequencing (RNA-seq) analysis of BC cells was performed to evaluate transcriptomic changes associated with miR-24-2-5p overexpression. Selected modulated transcripts upon miR-24-2-5p overexpression were further validated by real-time qPCR.ResultsLow expression levels of miR-24-2-5p, but not other miR-24 forms (miR-24-3p, miR-24-1-5p), in the serum from early-stage BC patients were associated with a high risk to develop future (bone) metastases. MiR-24-2-5p was also present in small extracellular vesicles secreted from BC cells. Forced expression of miR-24-2-5p in BC cells (NW1, MCF7) reduced their malignant traits (migration, invasion, and proliferation) in vitro. Furthermore, miR-24-2-5p overexpression in NW1 cells reduced metastasis, particularly in bone, and decreased bone turnover in vivo. RNA-seq and real-time qPCR analyses of NW1 and MCF7 cells overexpressing miR-24-2-5p showed the downregulation of common transcripts (CNNM4, DCTD, FMR1, PIGS, HLA-A, ICK, SH3BGRL2, WDFY, TRAF9B, IL6ST, PEX10, TRIM59). The conditioned medium from BC cells overexpressing miR-24-2-5p decreased human and murine osteoclast differentiation in vitro. Additionally, endogenous miR-24-2-5p expression levels in murine bone marrow-derived monocytes decreased during their differentiation into osteoclasts, further suggesting an inhibitory role for miR-24-2-5p during osteoclastogenesis.ConclusionMiR-24-2-5p exerts multiple protective roles in the early steps of BC bone metastasis by reducing malignant BC cell traits and tumour cell dissemination in bone, as well as by reducing the differentiation of precursors into mature osteoclasts.

Exploring glioma heterogeneity through omics networks: from gene network discovery to causal insights and patient stratification

Gliomas are primary malignant brain tumors with a typically poor prognosis, exhibiting significant heterogeneity across different cancer types. Each glioma type possesses distinct molecular characteristics determining patient prognosis and therapeutic options. This study aims to explore the molecular complexity of gliomas at the transcriptome level, employing a comprehensive approach grounded in network discovery. The graphical lasso method was used to estimate a gene co-expression network for each glioma type from a transcriptomics dataset. Causality was subsequently inferred from correlation networks by estimating the Jacobian matrix. The networks were then analyzed for gene importance using centrality measures and modularity detection, leading to the selection of genes that might play an important role in the disease. To explore the pathways and biological functions these genes are involved in, KEGG and Gene Ontology (GO) enrichment analyses on the disclosed gene sets were performed, highlighting the significance of the genes selected across several relevent pathways and GO terms. Spectral clustering based on patient similarity networks was applied to stratify patients into groups with similar molecular characteristics and to assess whether the resulting clusters align with the diagnosed glioma type. The results presented highlight the ability of the proposed methodology to uncover relevant genes associated with glioma intertumoral heterogeneity. Further investigation might encompass biological validation of the putative biomarkers disclosed.

Enhanced Antiglioma Effect by a Vitamin D3-Inserted Lipid Hybrid Neutrophil Membrane Biomimetic Multimodal Nanoplatform.

Glioblastoma, the most prevalent malignant brain tumor, is a lethal threat to human health, with aggressive and infiltrative growth characteristics that compromise the clinical treatment. Herein, we developed a vitamin D3-inserted lipid hybrid neutrophil membrane biomimetic multimodal nanoplatform (designated as NED@MnO2-DOX) through doxorubicin (DOX)-loaded manganese dioxide nanoparticles (MnO2) which were coated with a vitamin D3-inserted lipid hybrid neutrophil membrane. It was demonstrated that in addition to chemotherapy and chemo-dynamic therapy efficacy, NED@MnO2-DOX exhibited great power to activate and amplify immune responses related to the cGAS STING pathway, bolstering the secretion of type I interferon-β and proinflammatory cytokines, promoting the maturation of DC cells and infiltration of CD8+T cells into the glioma tissue, thereby reversing the immunosuppressive microenvironment of glioma from a "cold" tumor to a "hot" tumor. The biomimetic multimodal nanoplatform has potential as a multimodal strategy for glioma-targeted treatment, especially holding considerable promise for the development of innate immune therapy for glioma.

Incidence of and Risk Factors for Cutaneous Malignant Neoplasms After Blood or Marrow Transplant.

Cutaneous malignant neoplasms are the most common subsequent neoplasm after blood or marrow transplant (BMT), but a full assessment among survivors is lacking. To identify risk factors for subsequent cutaneous malignant neoplasms using the BMT Survivor Study (BMTSS). This retrospective cohort study included patients who underwent transplant from 1974 to 2014 at City of Hope, University of Minnesota, or University of Alabama at Birmingham and survived 2 years or longer, as well as a comparison cohort of siblings. Both groups completed the BMTSS survey. Data analysis took place from October 2022 to October 2024. Demographics, pre-BMT and BMT-related therapeutic exposures, chronic graft-vs-host disease (cGVHD), and posttransplant immunosuppression. Incident cutaneous malignant neoplasms (basal cell carcinoma [BCC], squamous cell carcinoma [SCC], and melanoma) after BMT. Exposures were evaluated for association with subsequent neoplasms using proportional subdistribution hazards models (reported as subdistribution hazard ratio [SHR] and 95% CI). Among the 3880 BMT survivors (median [range] age at BMT, 44.0 [0-78.0] years; 2165 [55.8%] male; 190 [4.9%] Black, 468 [12.1%] Hispanic, 2897 [74.7%] non-Hispanic White, and 325 [8.4%] of other race [including Asian and Pacific Islander] and multiracial) who were followed up for a median (range) of 9.5 (2.0-46.0) years, 605 developed 778 distinct cutaneous neoplasms (BCC, 321; SCC, 231; melanoma, 78; and unknown type, 148). The 30-year cumulative incidence of any cutaneous malignant neoplasm was 27.4% (BCC, 18.0%; SCC, 9.8%; and melanoma, 3.7%). Seventy-year cumulative probabilities of BCC, SCC, and melanoma were considerably higher in BMT survivors than siblings (18.1% vs 8.2%, 14.7% vs 4.2%, and 4.2% vs 2.4%, respectively). Among BMT survivors, risk factors for subsequent cutaneous malignant neoplasms included age of 50 years and older at BMT (BCC: SHR, 1.76; 95% CI, 1.36-2.29; SCC: SHR, 3.37; 95% CI, 2.41-4.72), male sex (BCC: SHR, 1.39; 95% CI, 1.10-1.75; SCC: SHR, 1.85; 95% CI, 1.39-2.45), pre-BMT monoclonal antibody exposure (BCC: SHR, 1.71; 95% CI, 1.27-2.31), allogeneic BMT with cGVHD (BCC: SHR, 1.48; 95% CI, 1.06-2.08; SCC: SHR, 2.61; 95% CI, 1.68-4.04 [reference: autologous BMT]), post-BMT immunosuppression (BCC: SHR, 1.63; 95% CI, 1.24-2.14; SCC: SHR, 1.48; 95% CI, 1.09-2.02; melanoma: SHR, 1.90; 95% CI, 1.16-3.12), and transplant at City of Hope (BCC: SHR, 3.55; 95% CI, 2.58-4.89; SCC: SHR, 3.57; 95% CI, 2.34-5.47 [reference: University of Minnesota]) or University of Alabama at Birmingham (BCC: SHR, 2.35; 95% CI, 1.35-4.23; SCC: SHR, 2.63; 95% CI, 1.36-5.08 [reference: University of Minnesota]). Race and ethnicity other than non-Hispanic White were protective for BCC (Black: no cases; Hispanic: SHR, 0.27; 95% CI, 0.16-0.44; other race and multiracial: SHR, 0.26; 95% CI, 0.14-0.50 [reference: non-Hispanic White]) and SCC (Black: SHR, 0.17; 95% CI, 0.04-0.67; Hispanic: SHR, 0.28; 95% CI, 0.16-0.50; other race and multiracial: SHR, 0.13; 95% CI, 0.05-0.37 [reference: non-Hispanic White]). Total body irradiation was associated with BCC risk among those younger than 50 years at BMT (SHR, 1.92; 95% CI, 1.27-2.92). In this cohort study, the high risk of cutaneous malignant neoplasms and malignant-specific risk factors suggest a need for personalized patient counseling and posttransplant dermatologic surveillance.

Genomic characterization and histologic analysis of uterine leiomyosarcoma arising from leiomyoma with bizarre nuclei.

Leiomyoma with bizarre nuclei (LM-BN) is a rare variant of leiomyoma with a benign clinical course. In contrast, leiomyosarcoma (LMS) is a high-grade, malignant neoplasm characterized by high recurrence rates and poor survival. While LM-BN and LMS show distinct morphologies, they share similar immunoprofiles and molecular alterations, with both considered 'genomically unstable'. Rare cases of LM-BN associated with LMS have been reported; however, the histogenesis and molecular relationship between these two tumors remains unclear. In this study, we assessed 11 cases of LMS arising in conjunction with LM-BN confirmed by histology and immunohistochemistry (IHC), further analyzed by clinical, histologic, and molecular characteristics of these distinct components. LM-BN and LMS had similar p16 and p53 IHC patterns, but LMS had a higher Ki-67 index and lower estrogen and progesterone eceptor expression. Digital image analysis based on cytologic features revealed spatial relationships between LMS and LM-BN. Genomic copy number alterations (CNAs) demonstrated the same clonal origin of LMS arising from existing LM-BN through conserved CNAs. LMS harbored highly complex CNAs and more frequent losses of the TP53, RB1, and PTEN genomic regions than LM-BN (p = 0.0031), with CDKN2A/B deletion identified in LMS only. Mutational profiling revealed many shared oncogenic alterations in both LM-BN and LMS; however, additional mutations were present within LMS, indicative of tumor progression through progressive genomic instability. Analysis of spatial transcriptomes defined uniquely expressed gene signatures that matched the geographic distribution of LM-BN, LMS, and other cell types. Our findings indicate for the first time that a subset of LMS arises from an existing LM-BN, and highly complex genomic alterations could be potential high risks associated with disease progression in LM-BN. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Long-term evaluation of Elmelegy’s technique of local muscle transposition for the functional restoration of large upper or lower lip defects

BackgroundAlthough more than 200 techniques have been reported for the reconstruction of the upper and lower lip defects since 1000 BC, none of them is ideal.Local flaps may result in extra skin incisions and in some cases, the surgeon may be confronted with the lack of sufficient tissues for the reconstruction of large defects.Several techniques have been described for near-total lip reconstruction. The two major available techniques are local flap reconstruction (Bernard–von Burrow–Webster technique) and free micro-vascular tissue transfer.In this study, we are going to evaluate the functional results of using local muscles transposition-assisted dermal fat flap and muco-buccal flap in the treatment of large upper or lower lip defects.Materials and methodsThis study was carried out on 128 patients, who presented to us with malignant tumors affecting the lips.ResultsLip defect sizes ranged from 4 to 6 cm in diameter. No flap failure was seen and desirable function and accepted esthetic results were obtained. The flap survival was 100%, and healing was eventful in all cases. No cases of microstomia were reported.ConclusionThe use of local muscle transposition-assisted dermal fat flap and muco-buccal flap technique, showed excellent results in regaining oral competence and lip mobility, and as much as possible, increased the aesthetic outcome.Level of evidenceIV therapeutic study.

LAT4 drives temozolomide induced radiotherapy resistance in glioblastoma by enhancing mTOR pathway activation

BackgroundGlioblastoma multiforme (GBM) represents the most prevalent form of primary malignant tumor within the central nervous system. The emergence of resistance to radiotherapy and chemotherapy represents a significant impediment to advancements in glioma treatment.MethodsWe established temozolomide (TMZ)-resistant GBM cell lines by chronically exposing U87MG cell lines to TMZ, and dimethyl sulfoxide (DMSO) was used as placebo control. In vivo and in vitro experiments verified the resistance of resistant cells to chemotherapy and radiotherapy. LAT4 was identified by transcriptomics to be associated with GBM treatment resistance and relapse. The relationship between LAT4 and mTOR pathway activity was also analyzed. Finally, the effect of BCH (LAT inhibitor) combined with radiotherapy on GBM prognosis was verified in vivo.ResultsWe have first confirmed that TMZ not only induces resistance to chemotherapy in GBM cells but also enhances their resistance to radiotherapy, which is a significant finding in the process of building TMZ-resistant U87MG GBM cell lines. We then performed comprehensive transcriptomic analysis and identified amino acid metabolism as a potential key factor in radiotherapy resistance. Specifically, we confirmed that the upregulation of LAT4 following chemotherapy enhances leucine metabolism within tumors in vitro and in vivo, thereby modulating the mechanistic target of mTOR pathway and leading to radiotherapy resistance. Of note, the application of inhibitors targeting leucine metabolism was shown to restore the sensitivity of these cells to radiotherapy, highlighting a potential therapeutic strategy for overcoming resistance in GBM.ConclusionsOur study links tumor sensitivity to chemotherapy and radiotherapy and highlights the critical role of LAT4 in activating the mTOR pathway and GBM radiotherapy resistance. It suggests ways to improve radiotherapy sensitivity to GBM.

Evaluation of functional magnetic resonance APT and DKI imaging for breast cancer

ObjectiveThis study aimed to compare the performance of amide proton transfer–weighted imaging (APTWI) and diffusion kurtosis imaging (DKI) in differentiating benign from malignant breast lesions, evaluate molecular subtypes of breast cancer, and determine the diagnostic efficacy of the quantitative magnetic resonance imaging (qMRI) parameters in differentiating benign from malignant breast diseases.MethodsThe study included 168 women who underwent breast APTWI and DKI at Yunnan Cancer Hospital between December 2022 and July 2023. The APT signal intensity (SI), apparent kurtosis coefficient (Kapp), non-Gaussian diffusion coefficient (Dapp), and apparent diffusion coefficient (ADC) values were measured before surgery. The differences in the aforementioned qMRI parameters in molecular subtypes of breast cancer were analyzed using one-way analysis of variance. The efficacy of each quantitative parameter in differentiating benign from malignant breast diseases was evaluated using the receiver-operating characteristic curve.ResultsSignificant differences in qMRI parameters were noted between benign and malignant breast lesions. The Kapp (P < .0001) and APT (P < .05) values were higher for malignant tumors than for benign lesions. Conversely, the ADC (P < .0001) and Dapp (P < .0001) values were lower for malignant tumors than for benign lesions. The diagnostic performance was assessed using the area under the curve (AUC) for various parameter combinations. The AUC of Kapp was 0.871, Dapp was 0.872, APT SI was 0.643, DKI + APT was 0.893, DKI + ADC was 0.936, APT + ADC was 0.925, and DKI + APT + ADC was 0.933. Additionally, ADC values (P = .01) demonstrated superior diagnostic performance compared to Kapp (P = .03), Dapp (P = .03), and APT values (P = .06) in distinguishing between different molecular subtypes of breast cancer.ConclusionsAPTWI distinguished benign from malignant breast disease and enhanced the utility of diffusion-weighted MRI. However, it was not superior to DKI and DWI in identifying the molecular subtypes of breast cancer.