Malignant Research Articles

Radiotherapy-Associated Cellular Senescence and EMT Alterations Contribute to Distinct Disease Relapse Patterns in Locally Advanced Cervical Cancer.

A notable number of locally advanced cervical carcinoma (LACC) patients experience local or distant disease relapse following radiotherapy. The contribution of tumor microenvironment (TME) to tumor recurrence at different sites remains unclear. Here, single-nucleus RNA sequencing data from 28 pre- and on-treatment LACC samples from patients with different disease relapse patterns is analyzed. The findings revealed opposing alterations in the expression levels of the cellular senescence pathway after radiotherapy in patients with local and distant relapses. In contrast, an increase in the expression of the epithelial-mesenchymal transition module after radiotherapy in both relapse groups is observed. Cell-cell interactions, drug-target expression analyses in malignant cells after radiation, and multiplex immunofluorescence of tumor tissue identified interleukin-1 receptor type I (IL1R1) as a potential therapeutic target. It is demonstrated that combining the IL1R1 inhibitor anakinra with radiation can mitigate the effects of radiation on tumor cells. This study highlights the distinct roles of cellular senescence and EMT in tumor recurrence.

Au@Fe3O4 Nanoparticle-Based Colorimetric Aptasensor for Noninvasive Screening of Colorectal Cancer via Detection of Parvimonas micra.

Colorectal cancer (CRC) is a common malignancy requiring early screening to improve patient outcomes. Current screening methods such as colonoscopy and fecal occult blood tests have several limitations including high cost, poor specificity, invasiveness, and inconvenience. Recent research has identified specific bacterial communities associated with CRC, notably Parvimonas micra (P. micra), which serves as a biomarker for early screening and diagnosis owing to its accumulation in the malignant tissues and feces of CRC patients. Herein, we employed the whole-bacterium systematic evolution of ligands by the exponential enrichment (SELEX) method to isolate high-affinity aptamers against P. micra using 17 selection cycles. These aptamers were subsequently bound to Au@Fe3O4 nanoparticles, and the interaction of P. micra and aptamers inhibited the peroxidase-like activity of Au@Fe3O4 nanoparticles, thereby blocking the 3,3',5,5'-tetramethylbenzidine (TMB) chromogenic reaction and resulting in a measurable reduction in absorbance. This colorimetric detection strategy demonstrated a linear response across a range of 100-108 CFU/mL for P. micra with a limit of detection of 11 CFU/mL. Using a colorimetric aptasensor, we assessed the abundance of P. micra in clinical fecal samples and found significantly higher levels in the feces of CRC patients as compared to that of healthy individuals, which was consistent with the quantitative polymerase chain reaction results. This study therefore represents the first successful identification of an aptamer with high affinity and specificity for P. micra, leading to the development of a highly specific and sensitive aptasensor for its detection. The presented approach has a significant potential for CRC screening and diagnosis.

Personalized prediction of acute pancreatitis after endoscopic transpapillary interventions

To develop the personalized model for predicting the risk of acute pancreatitis after endoscopic transpapillary interventions. A retrospective analysis of treatment outcomes included 366 patients with benign and malignant pancreaticobiliary diseases who underwent endoscopic transpapillary interventions. Risk factors associated with patients, underlying diseases and interventions were analyzed. Logistic regression analysis was used to present the personalized model for predicting the risk of acute pancreatitis. Female gender (p=0.028), age <40 years (p=0.001-0.018), calculous cholecystitis (p=0.010) and stenosis of the major duodenal papilla (p=0.008) are patient-associated risk factors of acute postoperative pancreatitis. Stenting of the main pancreatic duct and thoracic epidural analgesia reduced this risk by 6.5 and 4.6 times, respectively. We developed significant (p<0.001) regression model to determine the likelihood of acute post-manipulation pancreatitis. Original prediction model is valuable to determine the risk of acute pancreatitis after endoscopic transpapillary interventions. This model justifies various methods to prevent this complication.

BRD9 promotes the malignant phenotype of thyroid cancer by activating the MAPK/ERK pathway

Thyroid cancer is one of the most common endocrine gland malignancies in China. During gene transcription, the bromodomain and extraterminal domain (BET) proteins perform epigenome interpretation tasks. Bromodomain-containing protein 9 (BRD9) is one of the BET family members. Increasing evidence has implicated that BRD9 plays significant roles in multiple malignancies. However, its role in thyroid cancer is still not fully understood. In this research, our results demonstrated that high expression of BRD9 can facilitate the malignant phenotype of thyroid cancer cell lines, while low expression of BRD9 can impede the malignant phenotype of thyroid cancer cell lines. Pharmacologically, I-BRD9 treatment inhibits the proliferation and promotes the rate of apoptosis in thyroid cancer cell lines. Moreover, our results also revealed that BRD9 promoted xenograft tumor growth. In addition, our study showed that the expression of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) pathway-related proteins was decreased in BRD9 knockdown thyroid cancer cells, such as Raf, ERK, p-ERK, c-Fos, and c-Myc, which could be significantly reversed by overexpressing the BRD9 in different thyroid cancer cells. After the specific inhibitor of ERK (SCH772984) was applied to thyroid cancer cells (BCPAP cells) overexpressing the BRD9 gene, the results suggested that SCH772984 reverses the high expression of MAPK/ERK pathway-associated protein in BCPAP cells (over-expression BRD9 cells). In conclusion, this study demonstrated that BRD9 was highly expressed in serum and malignant tumor tissues of thyroid cancer patients and further promoted the development of the malignant phenotype of thyroid cancer by activating the MAPK/ERK signaling pathway.

MONet: cancer driver gene identification algorithm based on integrated analysis of multi-omics data and network models

Cancer progression is orchestrated by the accrual of mutations in driver genes, which endow malignant cells with a selective proliferative advantage. Identifying cancer driver genes is crucial for elucidating the molecular mechanisms of cancer, advancing targeted therapies, and uncovering novel biomarkers. Based on integrated analysis of Multi-Omics data and Network models, we present MONet, a novel cancer driver gene identification algorithm. Our method utilizes two graph neural network algorithms on protein-protein interaction (PPI) networks to extract feature vector representations for each gene. These feature vectors are subsequently concatenated and fed into a multi-layer perceptron model (MLP) to perform semi-supervised identification of cancer driver genes. For each mutated gene, MONet assigns the probability of being potential driver, with genes identified in at least two PPI networks selected as candidate driver genes. When applied to pan-cancer datasets, MONet demonstrated robustness across various PPI networks, outperforming baseline models in terms of both the area under the receiver operating characteristic curve and the area under the precision-recall curve. Notably, MONet identified 37 novel driver genes that were missed by other methods, including 29 genes such as APOBEC2, GDNF, and PRELP, which are corroborated by existing literature, underscoring their critical roles in cancer development and progression. Through the MONet framework, we successfully identified known and novel candidate cancer driver genes, providing biologically meaningful insights into cancer mechanisms.

Sarcoma of the descending aorta: a case report

Introduction: Primary malignant aortic tumors are rare and diagnosis can be difficult due to the variety of clinical manifestations. This malignant disease, which originates in the intima or medial layers of the aorta, presents a complex diagnostic and therapeutic dilemma. Due to their insidious growth and nonspecific symptoms, they are often diagnosed postmortem. Case presentation: We present the case of a sarcoma of the descending part of thoracic aorta in a 69-year-old man. The initial symptoms were hypertension crisis, chest pain, shortness of breath and swollen legs. A computed tomography scan of the chest and abdomen revealed an obstructive mass in the thoracic aorta. Treatment consisted of performing a prosthesis of the thoracic aorta and removal of thrombi/tumor masses from the thoracoabdominal aorta and iliac artery on both sides, as well as chemotherapy. Conclusion: Aortic sarcoma should be recognized as a potential cause of a large thrombus in the aorta. Palliative procedures, including open aortic replacement may also serve as alternative treatment options for aortic sarcoma. Introduction Primary malignant aortic tumors are rare and the diagnosis can be challenging due to the variety of clinical manifestations. We report here a rare case of intimal sarcoma that presented as a coarctation-like syndrome. Moreover, we review the literature and discuss the diagnostic approach, treatment options, and prognosis.

Ribosomal Proteins as Exosomal Cargo: Random Passengers or Crucial Players in Carcinogenesis?

Many ribosomal proteins (RPs) have functions beyond their canonical role as constituents of the ribosome. They often relate to human pathologies, primarily, to carcinogenesis, and the expression of specific RPs is considerably changed in malignant cells. On the other hand, extracellular vesicles (including exosomes), which provide intercellular communication by transporting specific molecular cargo from donor to recipient cells, often contain specific sets of RPs. Thus, one can assume that oncogenic properties of RPs can be transferred from one cell to another by exosomes. Such kind transfer has been already documented with RPS3 and gastric cancer cells. However, it remains largely unclear how widespread is the above effect and to which extent it contributes to the tumor progression and metastasis. To shed light on this issue, a comparative analysis of the sets of RPs found in exosomes and of the available data on oncogenic properties of these proteins is conducted.

Lactoferrin-Derived Peptide Chimera Induces Caspase-Independent Cell Death in Multiple Myeloma

Lactoferrin-derived peptide chimera is a synthetic peptide that mimics the functional unit of lactoferrin with antibacterial activity. Although LF has anticancer effects, to the best of our knowledge, its effects on multiple myeloma have not yet been studied. We explored the potential of a lactoferrin-derived chimera for multiple myeloma treatment, a malignant clonal plasma cell bone marrow disease. The lactoferrin-derived chimera effectively inhibited MM1S, MM1R, and RPMI8226 multiple myeloma cell growth, and induced the early and late phases of apoptosis, but not in normal peripheral blood mononuclear cells. Furthermore, the lactoferrin-derived chimera modulates the relative expression of genes involved in survival, apoptosis, and mitochondrial dysfunction at the transcriptional level. Mitochondrial analysis revealed that lactoferrin-derived chimera triggered oxidative stress in multiple myeloma cells, leading to reactive oxygen species generation and a decline in mitochondrial membrane potential, resulting in mitochondrial dysfunction. Although lactoferrin-derived chimera did not cause caspase-dependent cell death, it induced nuclear translocation of apoptosis-inducing factor and endonuclease G, indicating the initiation of caspase-independent apoptosis. Overall, the lactoferrin-derived chimera induces caspase-independent programmed cell death in multiple myeloma cell lines by increasing the nuclear translocation of apoptosis-inducing factor/endonuclease G. Therefore, it has potential for multiple myeloma cancer therapies.

The HRAS-binding C2 domain of PLCη2 suppresses tumor-like synoviocytes and experimental arthritis in rheumatoid arthritis.

Fibroblast-like synoviocytes (FLSs), which are stromal cells that play key roles in rheumatoid arthritis (RA) pathophysiology, are characterized by a tumor-like phenotype and immunostimulatory actions. C2 domains in various proteins play roles in intracellular signaling and altering cellular characteristics, and some C2 domain-containing proteins exacerbate or alleviate certain malignant or inflammatory diseases. However, the roles of C2 domains in regulating the functions of RA FLSs remain unclear. Here we performed functional C2 domainomics with 144 C2 domain-containing viral vectors and identified the C2 domain of PLCη2 as a key regulator of RA FLSs. In mice, overexpressing PLCη2 or only its C2 domain PLCη2 (PLCη2_C2) diminished the proliferation, migration, invasion and inflammatory responses of RA FLSs, mitigating RA pathology; the absence of PLCη2 amplified these proinflammatory and destructive processes in RA FLSs in vivo. Mechanistically, PLCη2 and PLCη2_C2 participate in the pathological signaling of RA FLSs in a calcium-independent manner through protein-protein interactions. Specifically, PLCη2_C2 disrupted HRAS-RAF1 interactions, suppressing downstream signaling pathways, including the NF-κB, JAK-STAT and MAPK pathways. Collectively, these findings establish PLCη2 and PLCη2_C2 as novel inhibitory regulators in RA, suggesting promising therapeutic avenues for addressing FLS-driven disease mechanisms.

Screening of the Antimelanoma Activity of Monoterpenes—In Vitro Experiments on Four Human Melanoma Lines

(1) Malignant melanoma is the most aggressive type of malignant tumor caused by a dysfunction of melanocytes. Despite progress in the treatment of melanoma, further research and search for new potential drugs are necessary to optimize the therapy. (2) The aim of this study was to evaluate the antiproliferative activity of eight selected monoterpenes by MTT and LDH assays on four malignant melanoma cell lines. (3) Myrcene, rhodinol and nerol did not show any significant anticancer effect on melanoma cell lines, but citral, carvacrol, citronellol, thymol and geraniol showed a significant anti-viability effect. Our studies have shown that the most effective terpene among those tested in inhibiting melanoma cell viability was carvacrol, with the lowest IC50 in the range of 0.05 ± 0.00 to 0.06 ± 0.01 mM. Moreover, it did not negatively affect normal human keratinocyte cells. (4) Metastatic melanoma is very difficult to treat, and some terpenes have the ability to sensitize cells to other chemicals; so, it is worth investigating their antimelanoma potential, as terpenes could become an adjuvant to traditional treatment.

Identification of tumor microenvironment-based gene prognostic signature with promising predictive value for chemo‐immunotherapy outcomes in lung adenocarcinoma patients

Objectives: The tumor microenvironment (TME) plays a critical role in tumor progression and therapeutic response. We aimed to establish a TME-associated gene signature for lung adenocarcinoma (LUAD) patients. Materials and Methods: We comprehensively analyzed the gene expression data of 513 LUAD patients deriving from The Cancer Genome Atlas (TCGA) database. To estimate the composition of TME, The Estimation of Stromal and Immune cells in malignant tumor tissue using the Expression data (ESTIMATE) algorithm was used. We then utilized protein-protein interaction (PPI) analysis, LASSO, and COX regression to explore the related candidate genes with survival. Eventually, a three-gene signature was constructed for risk stratification. Furthermore, we investigated its predictive value in advanced LUAD patients who received chemotherapy alone or combined with anti-PD-1 inhibitors. Results: We identified three genes, namely CCR2, CD40LG, and CCL21, to construct a TME-associated risk stratification gene signature. This gene signature was independently linked to patients' overall survival (OS) among the TCGA dataset (HR, 1.99; 95% CI 1.36-2.93, p &lt; 0.001) and GEO dataset (HR, 1.62; 95%CI 1.19-2.20, p &lt; 0.001). The addition of anti-PD-1 inhibitor Siltuximab to chemotherapy resulted in significantly longer progression-free survival (PFS) in low-risk patients (HR, 0.33; 95% CI: 0.20 - 0.56, p &lt; 0.001) but not in those with high- risk (HR, 0.56; 95% CI:0.24 - 1.31, p = 0.173). Moreover, in patients who received Sintilimab combined with chemotherapy, PFS was significantly different between the high- and low-risk group (HR,1.958; 95%CI:1.079-3.555, p = 0.024), whereas no significant difference was found in chemotherapy alone treated patients (HR, 1.303; 95%CI: 0.610-2.784, p = 0.492). Conclusions: This study generated a three-gene prognostic signature based on TME-associated core genes in patients with LUAD. This gene signature has good value for prognosis prediction. In addition, this signature correlated with treatment outcomes among patients treated with chemotherapy combined with anti-PD1 therapy.

Breaking barriers: Smart vaccine platforms for cancer immunomodulation.

Despite significant advancements in cancer treatment, current therapies often fail to completely eradicate malignant cells. This shortfall underscores the urgent need to explore alternative approaches such as cancer vaccines. Leveraging the immune system's natural ability to target and kill cancer cells holds great therapeutic potential. However, the development of cancer vaccines is hindered by several challenges, including low stability, inadequate immune response activation, and the immunosuppressive tumor microenvironment, which limit their efficacy. Recent progress in various fields, such as click chemistry, nanotechnology, exosome engineering, and neoantigen design, offer innovative solutions to these challenges. These achievements have led to the emergence of smart vaccine platforms (SVPs), which integrate protective carriers for messenger ribonucleic acid (mRNA) with functionalization strategies to optimize targeted delivery. Click chemistry further enhances SVP performance by improving the encapsulation of mRNA antigens and facilitating their precise delivery to target cells. This review highlights the latest developments in SVP technologies for cancer therapy, exploring both their opportunities and challenges in advancing these transformative approaches.

Design and validation of ultra-compact metamaterial-based biosensor for non-invasive cervical cancer diagnosis in terahertz regime.

Cervical cancer belongs to the most dangerous types of cancers posing considerable threat to women's survival. It is most often diagnosed in the advanced stages as precancerous lesions are often symptom-free and difficult to identify. Microwave imaging, especially in terahertz (THz) range, is a convenient and noninvasive cancer detection tool. It enables characterization of biological tissues and discrimination between healthy and malignant ones. This study presents a novel triple-band biosensor based on metamaterials (MTMs). By leveraging unique properties of MTMs, the proposed biosensor operates as a perfect absorber. It exploits resonant modes in the THz spectrum to achieve remarkable sensitivity. Meticulous selection of the sensor geometry and dimensions enables efficient miniaturization. Meanwhile, utilization of frequency-domain data to detect refractive index changes improves resolution of cancerous tissue identification. Extensive numerical investigations corroborate its ability to carry out reliable early-stage cervical cancer diagnosis. This includes identification of the spatial extent of the malignant tissue. Excellent electrical properties of the sensor are accompanied by its compact size, which is highly desirable for non-invasive and portable applications.

Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model

Chronic lymphocytic leukemia (CLL) is a heterogeneous B cell malignancy characterized by the accumulation of functionally incompetent B lymphocytes. Despite the availability of highly effective treatments, CLL remains incurable, and the factors contributing to disease progression are not fully understood. Autoimmune complications frequently arise in CLL patients and are associated with poor clinical prognosis. This study investigates the connection between plasma cell-mediated autoimmunity and CLL progression using a mouse model that expresses an active Receptor Activator of NF-κB (RANK) in B cells (RK mice), where autoimmune manifestations coexist with CLL. Transcriptional profiling of RANK-driven leukemic cells revealed a more indolent form of CLL compared to the classical TCL1 model. The discovery of near-identical CDR3 regions in both plasma and CLL cells of RK mice suggests a shared progenitor and antigen driving both conditions. Deletion of Blimp-1, which prevents plasma cell differentiation, initially enhanced B1/CLL formation in young mice but nearly halted CLL progression, highlighting the significant influence of autoimmune complications on disease outcomes. This research underscores the intertwined nature of autoimmunity and CLL, suggesting that targeting inflammatory pathways could offer therapeutic potential for managing both conditions.

Sonic hedgehog medulloblastoma cells in co-culture with cerebellar organoids converge towards in vivo malignant cell states.

In the malignant brain tumor sonic hedgehog medulloblastoma (SHH-MB) the properties of cancer cells are influenced by their microenvironment, but the nature of those effects and the phenotypic consequences for the tumor are poorly understood. The aim of this study was to identify the phenotypic properties of SHH-MB cells that were driven by the nonmalignant tumor microenvironment. Human induced pluripotent cells (iPSC) were differentiated to cerebellar organoids to simulate the nonmaliganant tumor microenvironment. Tumor spheroids were generated from 2 distinct, long-established SHH-MB cell lines which were co-cultured with cerebellar organoids. We profiled the cellular transcriptomes of malignant and nonmalignant cells by performing droplet-based single-cell RNA sequencing (scRNA-seq). The transcriptional profiles of tumor cells in co-culture were compared with those of malignant cell monocultures and with public SHH-MB datasets of patient tumors and patient-derived orthotopic xenograft (PDX) mouse models. SHH-MB cell lines in organoid co-culture adopted patient tumor-associated phenotypes and showed increased heterogeneity compared to monocultures. Subpopulations of co-cultured SHH-MB cells activated a key marker of differentiating granule cells, NEUROD1 that was not observed in tumor monocultures. Other subpopulations expressed transcriptional determinants consistent with a cancer stem cell-like state that resembled cell states identified in vivo. For SHH-MB cell lines in co-culture, there was a convergence of malignant cell states towards patterns of heterogeneity in patient tumors and PDX models implying these states were non-cell autonomously induced by the microenvironment. Therefore, we have generated an advanced, novel in vitro model of SHH-MB with potential translational applications.

Cryptolepine-transferrin nanosystem preparation and the anticancer effects on human malignant glioblastoma U87MG cells.

In this study, the synthesis and characterization of the human transferrin (hTf)-cryptolepine complex nanostructure were performed. The interaction of hTf in the forms of native and nanostructures with cryptolepine was evaluated through various spectroscopic methods, molecular docking, and molecular dynamic (MD) simulation studies. Finally, the anticancer mechanisms of the prepared complex nanostructure on the Human malignant glioblastoma U87MG cell line and normal astrocytes were assessed using cell viability, RT-PCR, and ELISA assays. The data showed that hTf and hTf-cryptolepine complex nanostructures exhibited particle sizes of 149.37 ± 28.98 and 161.85 ± 33.44 nm, and average zeta potential values of -11.85 ± 1.98 and -23.87 ± 2.202 mV, respectively. It was also found that the drug release behavior from the hTf-cryptolepine complex nanostructures displayed a pH-sensitive pattern, demonstrating a strong correlation with the Higuchi model and a moderate correlation with the Korsmeyer-Peppas model. Spectroscopy and MD simulation studies revealed that the interaction of hTf and cryptolepine did not induce significant changes in the structure of the protein. Moreover, binding parameters were determined to be greater for hTf-cryptolepine complex nanostructures compared to the hTf-cryptolepine complex. Cellular assays showed that the calculated IC50 concentrations of cryptolepine, hTf-cryptolepine complex, and hTf-cryptolepine complex nanostructures in Human malignant glioblastoma U87MG cells were 16.1, 14.31, and 4.60 μM, respectively. Furthermore, it was demonstrated that Human malignant glioblastoma U87MG cells treated with hTf-cryptolepine complex nanostructures had a more significant increase in caspase-3 expression and activity compared to free cryptolepine or the hTf-cryptolepine complex. In conclusion, this paper may hold great promise for the introduction of bionanotherapeutics, which require further evaluation in future studies.

Haploidentical Stem Cell Transplantation With Dual Source of Cells and Post-Transplant Cyclophosphamide.

Dual sources of cells (DSC) with peripheral blood stem cell apheresis (PBSC) and surgical bone marrow (BM) for haploidentical hematopoietic cell transplantation (Hid-HCT) are used in China and some Asian countries. The experience of the Baltimore group for haploidentical transplant with post-transplant cyclophosphamide (PT-Cy) and reduced-intensity-conditioning (RIC) regimen used BM as a source of hematopoietic stem cells. We retrospectively analyzed 64 Hid-HCT with DSC and PT-Cy, RIC (n = 57), or myeloablative-conditioning (MAC) (n = 7), from two public health Brazilian centers, with a median follow-up of 23.3 months (6.7-45.4). The 49 malignant patients were 27/46 (58.7%) beyond the first remission or with no complete response, and three patients did not complete disease status evaluation before transplant. Eight of 62 patients (12.9%) had grade 2 or more Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI), and two patients had no HCT-CI classified. Cytomegalovirus (CMV) viremia occurred in 26 of 57 (45.6%). The cumulative incidence of 100-day grade III-IV acute GVHD was 12.3% (7/57), with a 95% confidence interval (CI) of 3.8% and 20.8%, and 2-year moderate or severe chronic GVHD was 21.1% (11/52; 95% CI, 10.1%-32.3%). The 2-year relapses were 24.5% for malignant disease (12/49; 95% CI, 12.4%-36.5%). The 2-year overall survival (OS) probability was 54.7% (35/64; 95% CI, 42.5%-66.9%). Benign diseases achieve 2-year OS in 73.3% (11/15; 95% CI, 51%-95.7%) of the patients. The HCT-CI were significant in multivariate analyses for DFS (p = 0.002) and OS in uni- and multivariate analyses (both p < 0.001). The number of CD34+ cells by apheresis collection was significant in multivariate analysis for DFS (p = 0.039). Hid-HCT using PT-Cy, DSC, and RIC is a safe option for benign and malignant diseases.

IoT based Predictive Modeling Techniques for Cancer Detection in Healthcare Systems

Background: The main objective of the Internet of Things (IoT) has significantly influenced and altered technology, such as interconnection, interoperability, and sensor devices. To ensure seamless healthcare facilities, it's essential to use the benefits of ubiquitous IoT services to assist patients by monitoring vital signs and automating functions. In healthcare, the current stateof-the-art equipment cannot detect many cancers early, and almost all humans have lost their lives due to this lethal sickness. Hence, early diagnosis of cancer is a significant difficulty for medical experts and researchers. Methods: The method for identifying cancer, together with machine learning and IOT, yield reliable results. In the Proposed model FCM system, the SVM methodology is reviewed to classify either benign or malignant disease. In addition, we applied a recursive feature selection to identify characteristics from the cancer dataset to boost the classifier system's capabilities. Results: This method is being applied in conjunction with fuzzy cluster-based augmentation, and classification can employ continuous monitoring to forecast lung cancer to improve patient care. In the process of effective image segmentation, the fuzzy-clustering methodology is implemented, which is used for the goal of obtaining transition region data. Conclusion: The Otsu thresholding method is applied to help recover the transition region from a lung cancer image. Furthermore, morphological thinning on the right edge and the segmentationimproving pictures are employed to increase segmentation performance. In future work, we intend to design a prototype to ensure real-time analysis to provide enhanced results. Thus, this work may open doors to carry patent-based outcomes.

Allogeneic CD33-directed CAR-NKT cells for the treatment of bone marrow-resident myeloid malignancies

Chimeric antigen receptor (CAR)-engineered T cell therapy holds promise for treating myeloid malignancies, but challenges remain in bone marrow (BM) infiltration and targeting BM-resident malignant cells. Current autologous CAR-T therapies also face manufacturing and patient selection issues, underscoring the need for off-the-shelf products. In this study, we characterize primary patient samples and identify a unique therapeutic opportunity for CAR-engineered invariant natural killer T (CAR-NKT) cells. Using stem cell gene engineering and a clinically guided culture method, we generate allogeneic CD33-directed CAR-NKT cells with high yield, purity, and robustness. In preclinical mouse models, CAR-NKT cells exhibit strong BM homing and effectively target BM-resident malignant blast cells, including CD33-low/negative leukemia stem and progenitor cells. Furthermore, CAR-NKT cells synergize with hypomethylating agents, enhancing tumor-killing efficacy. These cells also show minimal off-tumor toxicity, reduced graft-versus-host disease and cytokine release syndrome risks, and resistance to allorejection, highlighting their substantial therapeutic potential for treating myeloid malignancies.

Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma-A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone.

Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care. Autophagic protein degradation is currently not targeted in myeloma treatment. This Phase I trial showed that the combination of the proteasome inhibitor carfilzomib and the autophagy inhibitor hydroxychloroquine was well tolerated in patients with relapsed/refractory multiple myeloma. Adverse events were mostly Grades 1 and 2. An overall response rate of 44% indicates a meaningful clinical efficacy of this combination. Trial Registration: The study was registered at clinicaltrials.gov # NCT04163107.