Malignant Research Articles

Extramedullary plasmacytoma with the uvula as first affected site: A case report

BACKGROUND Extramedullary plasmacytoma (EMP) represents one of the rarer forms of plasma cell malignancies, capable of impacting a variety of tissues and organs throughout the body. The majority of EMP cases are predominantly found in the head and neck region, especially within the laryngopharynx, as well as in the gastrointestinal tract. While there have been documented instances of oropharyngeal involvement in EMP cases in the academic literature, it is important to note that EMP specifically affecting the uvula is exceedingly uncommon. Furthermore, it is noteworthy that over 60% of epithelial carcinomas in the upper respiratory tract and oropharynx tend to metastasize to the cervical lymph nodes, indicating a propensity for regional spread in these types of cancers. In this context, we present a rare case of extramedullary plasmacytoma where the uvula served as the initially affected site. This case emphasizes the need for heightened awareness among clinicians regarding such unusual comorbidities, as early recognition and diagnosis can significantly influence patient management and treatment outcomes. In addition, a review of the relevant literature is included to further educate and inform healthcare professionals about this rare presentation, ultimately aiming to enhance clinical understanding and improve patient care in similar situations. CASE SUMMARY A 51-year-old man was admitted to our hospital because of a slowly enlarging neck mass. A physical examination revealed a palpable left lymph node, and magnetic resonance imaging (MRI) of the oropharynx and the neck showed a soft tissue mass in the oropharynx and enlargement of multiple lymph nodes in the neck. The soft tissue mass was diagnosed as plasmacytoma by immunohistochemical analysis. Monoclonal immunoglobulins and bone marrow biopsy showed normal results. Therefore, we diagnosed that as EMP of the uvula. After four cycles of adjuvant chemotherapy dominated by bortezomib, MRI reexamination showed a significant reduction of the mass in the oropharynx and the cervical lymph nodes. Afterwards, the λ light chain returned to normal levels. There was no evidence of evolution to multiple myeloma. CONCLUSION We have reported a rare case of extramedullary plasmacytoma with the uvula as the first affected site and the relevant literature is reviewed to improve clinicians' awareness of such rare comorbidities.

Current Situation and Management of Pleural Effusion in PHI Clinical Hospital Tetovo

Introduction: Pleural effusion is a disturbance in the balance between fluid production and elimination in the pleural space, resulting in abnormal fluid accumulation. It can result from various medical conditions related to the lungs and pleura or systemic diseases. Identifying the etiology of pleural effusion is essential for effective treatment. According to Light's criteria, pleural effusions are transudative and exudative. Material and Methods: For this research, we collected data from the existing documentation in the Department of Pulmonology and Respiratory Allergology at PHI Clinical Hospital Tetovo from June 2022 to June 2023. This study included 133 patients with dyspnea, persistent chest pain, fatigue, hemoptysis, cough, a history of past illnesses, and other comorbid conditions. The data collection process was rigorous, and we followed ethical guidelines to ensure the reliability of our findings. Results: The patients included in our study were between 36 to 84 years old. Of them, 72,9% were males, and 27,1% were females. 85,7% were smokers, and 14,3% were non-smokers. 75,0% of patients complained of dyspnea, and 24,8% had hemoptysis. From the ultrasonography findings, 15,0% had an alteration in the left lung, 11,3% in the right lung, 20,3% of patients were punctuated to the left side, and 24,8% were punctuated to the right lung. In comparison, 1,5% were punctuated to both sides. In 2,3% of the subjects, computed tomography described an effusion in the left lung. Conclusion: The results suggest that pleural effusion is associated with various diseases, especially heart failure and malignant diseases. Our study underscores the importance of early detection of the cause of pleural effusion and the underlying disease for successfully managing and treating the disease. The insights from our research can guide healthcare professionals in developing effective treatment strategies and improving patient outcomes.

Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells

The current study established the first in vitro Encorafenib resistance protocol in BRAF-mutated malignant melanoma (MM) cells and investigated the resistance-related mechanisms. After establishing Encorafenib-resistant A375-MM cells, resistant-related mechanisms were investigated using WST-1, Annexin V, cell cycle, morphological analysis, live-cell, Western blot, RNA-Seq, transmission electron microscopy-(TEM), oxidative stress and iron colorimetric assay. The most resistant group, called A375-R, was determined in the cells treated with a constant dose of 10 nM over 3 months. The viability, apoptosis, and G0/G1 arrest reflected the acquired chemoresistance. Autophagic Beclin and LC3 proteins, and AKT signaling increased in the A375-R. RNA-Seq results also exhibited altered epigenetic regulation of resistance; particularly ferritin family members, ion transport pathways. Then, increased NCOA4, FTH1, and iron levels detected in A375-R suggest that the iron metabolism-related mechanism, such as ferritinophagy, might be triggered, which was supported by TEM and oxidative stress analysis. Iron storage, transport, and ferritinophagy have the promising potential to be targeted for combining with BRAF-targeted therapy to reverse Encorafenib resistance in MM. Moreover, this is the first study evaluating in vitro Encorafenib resistance mechanisms, and we suggest that our findings contribute to improving new drug combinations targeting BRAF and iron metabolism in different MM cells.

Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases

Breast cancer is the most common malignant tumor in the world, and its metastasis is the main cause of death in breast cancer patients. However, the differences between primary breast cancer tissue and lymphatic node, bone, and brain metastases at the single-cell level are not fully understood. We analyzed the microenvironment heterogeneity in samples of primary breast cancer (n = 4), breast cancer lymphatic node metastasis (n = 4), breast cancer brain metastasis (n = 3), and breast cancer bone metastasis (n = 2) using single-cell sequencing data from the GEO database. The malignant epithelial cells were characterized by InferCNV algorithm. The cell-cell communication was analyzed using CellChat package. The biological function of cell subpopulations was analyzed using gene set variation analysis. The expression of STMN1 was analyzed using immunohistochemical staining. The proportion of pCAFs in breast cancer was explored using multispectral immunohistochemical staining. We identified seven cell clusters in primary and metastatic breast cancer (Lymphatic node, brain, and bone metastases) by analyzing single-cell transcriptomic profiles. T-NK and B cells dominated breast cancer with lymphatic node metastasis, whereas fibroblasts were prevalent in brain metastases and primary breast cancer. We identified five T cells (T memory, CD8 + T cells, regulatory T cells, natural killer cells, CD4 + T cells), three B cells (naïve B cells, memory B cells, plasma B cells), and five cancer-associated fibroblasts (CAFs) subpopulations (Smooth muscle cells (SMC), pericyte, antigen-presenting CAFs (apCAFs), proliferative CAFs (pCAFs), and matrix CAFs (mCAFs)). Notably. pCAFs dominated breast cancer with lymphatic node, bone, and brain metastasis. Furthermore, we identified four malignant epithelial cell subpopulations: G0, G1, G2, and G3. The G2 cell population exhibited strong invasion ability, it can differentiate into G3 with strong proliferative ability and proliferation-related G1 cell population after metastasis. Cell-cell communication demonstrated an interaction between pCAFs and metastasis-associated malignant epithelial cells. Finally, we discovered that in advanced breast cancer, the proportion of pCAF increased and was associated with a poor prognosis of breast cancer. This study elucidated the potential cellular origins and drivers of breast cancer metastases to lymphatic nodes, brain, and bone, utilizing single-cell transcriptomic profiles. Furthermore, it demonstrated that increased pCAFs were associated with advanced breast cancer and a poor prognosis.

The role of OCT4 and CD44 in lower lip carcinogenesis.

Carcinogenesis is characterized by the transformation of normal cells into malignant cells. Concerning the lower lip, exposure to UV radiation is the main etiological factor associated with the development of epidermoid carcinomas and actinic cheilitis. According to the hierarchical model theory, cancer development is driven by populations of cancer stem cells. In this context, this study aimed to compare the expression of octamer-binding transcription factor 4 (OCT4) and CD44 in 40 lower lip epidermoid carcinoma (LLEC) and 40 actinic cheilitis (AC) cases. OCT4 and CD44 expressions were assessed semi-quantitatively according to the percentage of positive epithelial cells (PP) and intensity of expression (IE), resulting in a total immunolabeling score (PIT). No statistically significant differences were detected between OCT4 and CD44 immunoexpression and clinicopathological parameters, except for lymph node metastasis, in which a decrease in CD44 expression in the core tumor of cases with lymph node metastasis was observed. Furthermore, decreased CD44 expression was observed in LLEC cases when compared to AC cases. The findings reported herein suggest a higher participation of CD44 in early carcinogenesis stages. In addition, the imbalance between OCT4 and CD44 immunoexpressions suggests the presence of different neoplastic cell subpopulations.

Clonal Hematopoiesis in Women With Breast Cancer.

Clonal hematopoiesis (CH) has been associated with a variety of adverse outcomes, most notably hematologic malignancy and ischemic cardiovascular disease. A series of recent studies also suggest that CH may play a role in the outcomes of patients with solid tumors, including breast cancer. Here, we review the clinical and biological data that underlie potential connections between CH, inflammation, and breast cancer, with a focus on the prevalence and impact of clonal hematopoiesis of indeterminate potential in patients with breast cancer. We summarize data from multiple studies, including a series of cohorts of patients with breast cancer, to assess the prevalence of CH, the relationship between CH and exposure to cytotoxic therapy, and the correlation between CH and breast cancer-specific outcomes. Our findings indicate that CH is prevalent among patients with breast cancer, particularly those treated with cytotoxic therapies. However, there are no definitive data to support an association between the presence of CH and breast cancer-specific outcomes. Current data do not support routine CH testing in patients with breast cancer, nor should the presence of CH influence decisions regarding breast cancer therapy in most patients. However, larger, long-term studies are necessary to further define the implications of CH in patients with breast cancer and guide clinical decision making.

Biological Effects of Calceolarioside A as a Natural Compound: Anti-Ovarian Cancer, Anti-Tyrosinase, and Anti-HMG-CoA Reductase Potentials with Molecular Docking and Dynamics Simulation Studies.

One kind of hydroxycinnamic acid is calceolarioside A. Plantago coronopus, Cassinopsis madagascariensis, and other organisms for whom data are available are known to have this naturally occurring compound. IC50 values of Calceolarioside A for ovarian cell lines (NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, UWB1.289) were 24.42, 13.50, 9.31, 14.90, 20.07, and 16.18µM, respectively. IC50 values were 19.83 and 73.48µM for tyrosinase and HMG-CoA reductase enzymes. The chemical activities of Calceolarioside A against HMG-CoA reductase and tyrosinase were assessed by conducting the molecular docking study, MM/GBSA calculation, and molecular dynamics (MD) simulation. The anticancer activities of this compound were evaluated against some ovarian cancer cells, such as NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, and UWB1.289 cell lines. The chemical activities of Calceolarioside A against some of the expressed surface receptor proteins (folate receptor, CD44, EGFR, Formyl Peptide Receptor-Like 1, M2 muscarinic receptor, and estrogen receptors) were investigated using computational methods. The results exhibited the interplay among atoms. The compound formed robust associations with both the enzymes and receptors. Calceolarioside A can hinder the functioning of these enzymes and the proliferation of malignant cells.

Predictive risk model of mild cognitive impairment in patients with malignant haematological diseases after haematopoietic stem cell transplantation

ObjectiveThis study is to develop and validate a robust risk prediction model for mild cognitive impairment (MCI) in patients with malignant haematological diseases after haematopoietic stem cell transplantation (HSCT).MethodsIn this study, we analysed the clinical data of the included patients. Logistic regression analysis was used to identify independent risk factors for cognitive impairment after HSCT in patients with malignant haematological diseases, and a risk prediction model was constructed. Multiple cohorts of patients with haematological malignancies after HSCT (282 cases) from the Affiliated Hospital of Xuzhou Medical University and the First People’s Hospital of Yancheng City between April 2019 and February 2022, and patients from the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University between March 2022 and July 2023 were used for external validation. Logistic regression analysis was performed to develop the predictive model. The predictive value and consistency of the model were evaluated using the area under the curve (AUC) and calibration method, respectively. Decision curve analysis (DCA) was performed to access the utility of the model.ResultsApproximately half (52.26%) of the patients in the study developed mild cognitive impairment (MCI). Older age, allogeneic HSCT, anxiety, graft-versus-host disease, and longer hospital stay were associated with a higher risk of developing MCI. ROC curve analysis confirmed the sound performance of the predictive model and external validation, with AUC of 0.897 and 0.789 respectively. The direction of the calibration curves of the training and validation sets is closer to the diagonal (ideal curve), indicating good model consistency; the DCA curves also show that the model has good predictive ability and stability.ConclusionsWe conclude that it is possible to predict mild cognitive impairment with readily available, mostly pretransplant predictors. The accuracy of the risk prediction models can be improved for use in clinical practice, possibly by adding pretransplant patient-reported functioning and comorbidities.

Identification and characterization of tumor and stromal derived liquid biopsy analytes in pancreatic ductal adenocarcinoma

BackgroundThe lack of predictive biomarkers contributes notably to the poor outcomes of patients with pancreatic ductal adenocarcinoma (PDAC). Cancer-associated fibroblasts (CAFs) are the key components of the prominent PDAC stroma. Data on clinical relevance of CAFs entering the bloodstream, known as circulating CAFs (cCAFs) are scarce. Here, we developed a combined liquid biopsy assay to detect cCAFs and circulating tumor cells (CTCs) in metastatic PDAC (mPDAC) and other metastatic gastrointestinal malignancies (mGI). In addition, we evaluated plasma hyaluronan (HA) levels as a complementary surrogate biomarker of the stromal extent in patients with PDAC.MethodsA sequential liquid biopsy assay based on a two step-enrichment, combining marker dependent and independent cell enrichment, was established for cCAF and CTC detection and validated in mPDAC and mGI patients. The enriched cells were identified by multiplex immunofluorescence. HA measurement was performed by ELISA on blood samples from healthy blood donors (HD), localized and late-stage PDAC patients.ResultscCAFs (≥ 1cCAFs/7.5 mL blood) were detected in 95.4% of mPDAC and in 78.2% of mGI patients, with significantly higher numbers in mPDAC compared to mGI patients (mean number 22.7 vs. 11.0; P = 0.0318). mPDAC patients with ≥ 15 cCAFs/7.5 mL blood had a significant shorter median overall survival (mOS 3.2 months (95% confidence interval (CI) 0.801–5.855) vs. 14.2 months (95% CI 6.055–22.332); P = 0.013), whereby CTC levels were not associated with mOS. In mGI neither cCAFs nor CTCs had a significant impact on OS. HA plasma levels in mPDAC patients were significantly higher compared to HD (mean 123.0 ng/mL vs. 74.45 ng/mL, P = 0.015). High HA in localized and late-stage PDAC were associated with a significantly shorter mOS (mOSlocalized PDAC: 12.6 months vs. 23.5 months (P = 0.008); mOSmPDAC: 1.8 months vs. 5.3 months (P = 0.004)).ConclusionsOur liquid biopsy assay provides robust detection of cCAFs in mPDAC and mGI patients. The measurement of both circulatory stromal parameters, cCAFs and HA, adds valuable clinical information as they are associated with an unfavorable outcome in PDAC. These results highlight that stromal characteristics unique to PDAC could be leveraged to fill the current gap in discovering predictive biomarkers.

Multiple Kinase Small Molecule Inhibitor Tinengotinib (TT-00420) Alone or With Chemotherapy Inhibit the Growth of SCLC.

There is an urgent need to develop new targeted treatment agents for small cell lung cancer (SCLC). Tinengotinib (TT-00420) is a novel, multi-targeted, and spectrally selective small-molecule kinase inhibitor that has shown significant inhibitory effects on certain solid tumors in preclinical studies. However, its role and mechanism of action in SCLC remain unclear. In this study, we demonstrated that tinengotinib effectively inhibited SCLC cell proliferation, especially highly expressing NeuroD1 (SCLC-N), in the SCLC cell line-derived xenograft (CDX) model and the malignant pleural effusion cell model of patients with SCLC. When combined with etoposide/cisplatin, it synergistically inhibited SCLC growth. Tinengotinib regulates proliferation, apoptosis, migration, cell cycle and angiogenesis in SCLC cells. Mechanistic studies revealed that c-Myc expression may be a key factor influencing the effect of tinengotinib in SCLC-N. This study provides reliable preclinical data and a new direction for tinengotinib as a promising therapy for SCLC, either alone or in combination with chemotherapy.

TRPM4 contributes to cell death in prostate cancer tumor spheroids, and to extravasation and metastasis in a zebrafish xenograft model system.

Transient receptor potential melastatin-4 (TRPM4) ion channel expression is upregulated in prostate cancer (PCa), contributing to increased cell proliferation, migration, adhesion, epithelial-to-mesenchymal transition, cell cycle shift, and alterations of intracellular Ca2+ signaling. GEO2R platform analysis of messenger RNA (mRNA) expression of ~ 6350 genes in normal and malignant prostate tissue samples from 15 PCa patients demonstrates that TRPM4 expression is upregulated sixfold and is among the most significantly upregulated genes in PCa. We find that absence of TRPM4 reduced PCa tumor spheroid size and decreased PCa tumor spheroid outgrowth. In addition, lack of TRPM4 increased cell death in PCa tumor spheroids, a phenotype that is absent in two-dimensional (2D) cancer cell systems. Lastly, absence of TRPM4 in PCa cells reduced extravasation and metastatic burden in a preclinical zebrafish cancer model. Taken together, our findings show that TRPM4 is an attractive therapeutic target in PCa and highlights the need for future development of pharmacological tools.

Single-cell and bulk RNA sequencing analysis reveals CENPA as a potential biomarker and therapeutic target in cancers.

Cancer remains one of the most significant public health challenges worldwide. A widely recognized hallmark of cancer is the ability to sustain proliferative signaling, which is closely tied to various cell cycle processes. Centromere Protein A (CENPA), a variant of the standard histone H3, is crucial for selective chromosome segregation during the cell cycle. Despite its importance, a comprehensive pan-cancer bioinformatic analysis of CENPA has not yet been conducted. Data on genomes, transcriptomes, and clinical information were retrieved from publicly accessible databases. We analyzed CENPA's genetic alterations, mRNA expression, functional enrichment, association with stemness, mutations, expression across cell populations and cellular locations, link to the cell cycle, impact on survival, and its relationship with the immune microenvironment. Additionally, a prognostic model for glioma patients was developed to demonstrate CENPA's potential as a biomarker. Furthermore, drugs targeting CENPA in cancer cells were identified and predicted using drug sensitivity correlations and protein-ligand docking. CENPA exhibited low levels of gene mutation across various cancers. It was found to be overexpressed in nearly all cancer types analyzed in TCGA, relative to normal controls, and was predominantly located in the nucleus of malignant cells. CENPA showed a strong association with the cancer cell cycle, particularly as a biomarker for the G2 phase. It also emerged as a valuable diagnostic and prognostic biomarker across multiple cancer types. In glioma, CENPA demonstrated reliable prognostic potential when used alongside other prognostic factors. Additionally, CENPA was linked to the immune microenvironment. Drugs such as CD-437, 3-Cl-AHPC, Trametinib, BI-2536, and GSK461364 were predicted to target CENPA in cancer cells. CENPA serves as a crucial biomarker for the cell cycle in cancers, offering both diagnostic and prognostic value.

Case report: A rare case of chondrosarcoma-like malignant giant cell tumor in adolescent rib: diagnostic challenges and treatment

Chondrosarcoma-like malignant giant cell tumor (GCT) of the rib is an extremely rare and aggressive tumor, particularly in adolescents. This case report describes a 19-year-old female presenting with a GCT of the rib with chondrosarcomatous differentiation, highlighting the challenges posed by its unusual location and pathological complexity. Multidisciplinary diagnostic approaches, including advanced imaging, immunohistochemistry (IHC), and pathology, were essential for confirming the diagnosis. Key IHC markers such as Vimentin, SMA, and CD163, alongside genetic analysis excluding H3F3A mutations, guided the diagnostic process. The patient underwent successful surgical resection, achieving early recovery without adjuvant therapy. This report underscores the importance of early detection, precise pathological evaluation, and individualized surgical treatment for rare and high-risk tumors, emphasizing the need for long-term follow-up to monitor recurrence.

Is There a Role for Daratumumab Retreatment in Patients with Relapsed/Refractory Multiple Myeloma?

Multiple myeloma (MM) is a hematologic disease characterized by the clonal expansion of malignant plasma cells that accumulate in the bone marrow, leading to osteolytic bone disease, hypercalcemia, anemia, and renal dysfunction. Daratumumab was the first monoclonal anti-CD38 antibody approved for the treatment of MM, initially in relapse/refractory settings and, more recently, for newly diagnosed patients. Increased first-line usage of daratumumab will also substantially change treatment approaches for patients with relapsed/refractory disease. Due to the cost and availability of bispecific T cell redirecting antibodies (BsAbs) and chimeric antigen receptor T cell therapy (CAR-T) in real-life settings in many countries, retreatment with daratumumab in subsequent lines of therapy might be a reasonable choice. Data regarding efficacy and optimal combinations of daratumumab retreatment are lacking, and here we provide a short literature review of available data. We identified only a small number of articles based on retrospective analysis of medical records in real-life settings. A strong consistency in results regarding response rates and treatment duration was noticed among mainly heavily pre-treated MM patients, with approximately half of patients achieving at least partial remission (PR) after retreatment with daratumumab-based protocol. The duration of treatment and time to the next treatment for retreatment episodes were considerable and consistent with clinical expectations for later lines of therapy. The analysis of data in this literature review indicates that daratumumab retreatment may provide meaningful clinical benefit to some patients with relapsed/refractory MM despite having prior exposure. However, further research is needed to identify clinical and biological parameters that may predict favorable responses to daratumumab retreatment.

Revolutionizing radiotherapy: gold nanoparticles with polyphenol coating as novel enhancers in breast cancer cells—an in vitro study

Breast cancer is the most common cancer among women, with over 1 million new cases and around 400,000 deaths annually worldwide. This makes it a significant and costly global health challenge. Standard treatments like chemotherapy and radiotherapy, often used after mastectomy, show varying effectiveness based on the cancer subtype. Combining these treatments can improve outcomes, though radiotherapy faces limitations such as radiation resistance and low selectivity for malignant cells. Nanotechnologies, especially metallic nanoparticles (NPs), hold promise for enhancing radiotherapy. Gold nanoparticles (AuNPs) are particularly notable due to their high atomic number, which enhances radiation damage through the photoelectric effect. Studies shown that AuNPs can act as effective radiosensitizers, improving tumor damage during radiotherapy increasing the local radiation dose delivered. Traditional AuNPs synthesis methods involve harmful chemicals and extreme conditions, posing health risks. Green synthesis methods using plant extracts offer a safer and more environmentally friendly alternative. This study investigates the synthesis of AuNPs using Laurus nobilis leaf extract and their potential as radiosensitizers in breast carcinoma cell lines (MCF-7). These cells were exposed to varying doses of X-ray irradiation, and the study assessed cell viability, morphological changes and DNA damage. The results showed that green-synthesized AuNPs significantly enhanced the therapeutic effects of radiotherapy at lower radiation doses, indicating their potential as a valuable addition to breast cancer treatment.

L-Asparaginase Immobilized on Nanographene Oxide as an Efficient Nanobiocatalytic Tool for Asparagine Depletion in Leukemia Cells.

l-Asparaginase (l-ASNase) catalyzes the hydrolysis of l-asparagine, leading to its depletion and subsequent effects on the cellular proliferation and survival. In contrast to normal cells, malignant cells that lack asparagine synthase are extremely susceptible to asparagine deficiency. l-ASNase has been successfully employed in treating pediatric leukemias and non-Hodgkin lymphomas; however, its usage in adult patients and other types of cancer is limited due to significant side effects and drug resistance. Recent research has explored alternative formulations and delivery methods to enhance its efficacy and minimize adverse effects. One promising approach involves the immobilization of l-ASNase onto nanostructured materials, offering improved enzymatic activity and biocompatibility of the support. We harnessed an E. coli l-ASNase type II preparation to develop a novel strategy of enzyme immobilization on graphene oxide (GO)-based support. We compared GO and nanographene oxide (nGO) in terms of their biocompatibility and influence on enzyme parameters. The obtained l-ASNase on the nGO nanobiocatalyst maintains enzymatic activity and increases its stability, selectively acting on K562 leukemia cells without cytotoxic influence on normal endothelial cells. In the case of treated K562 cells, we confirmed enlargement in the cell and nucleus size, disturbance in the cell cycle (interphase and metaphase), and increased apoptosis rate. The potential therapeutic possibilities of immobilized l-ASNase on leukemia cell damage are also discussed, highlighting the importance of further research in this area for advancing cancer therapy.

Diagnostic and Prognostic Value of Serum Vitronectin and Galectin-3 levels in Thyroid Tumors

Objective: Increased expression of Galectin-3(Gal-3) and Vitronectin (VN) molecules has been the subject of research, since it may be a biological marker that can be used for the separation of benign and malignant tissues. We aimed to evaluate serum Gal-3 and VN expression levels in the presence of thyroid tissue, and evaluate the predictive and prognostic value of these molecules in the differential diagnosis of malignant tissues. Materials and Methods: 44 patients with thyroid nodules were included in this prospective study. Benign and malignant lesions were distinguished from thyroidectomy materials. Results: Mean preoperative Gal-3 and VN values measured in malignant lesions were statistically significantly higher than preoperative Gal-3 and VN values in benign lesions (p-values: 0.007 and 0.009, respectively). Also, mean Gal-3 and VN values measured in serum were significantly reduced after operation compared to preoperative values (p-values

18F−Prostate−Specific Membrane Antigen PET/CT imaging for potentially resectable pancreatic cancer (PANSCAN−2): a phase I/II study

BackgroundCurrent diagnostic imaging modalities have limited ability to differentiate between malignant and benign pancreaticobiliary disease, and lack accuracy in detecting lymph node metastases. 18F-Prostate-Specific Membrane Antigen (PSMA) PET/CT is an imaging modality used for staging of prostate cancer, but has incidentally also identified PSMA-avid pancreatic lesions, histologically characterized as pancreatic ductal adenocarcinoma (PDAC). This phase I/II study aimed to assess the feasibility of 18F-PSMA PET/CT to detect PDAC.MethodsSeventeen patients with clinically resectable PDAC underwent 18F-PSMA PET/CT prior to surgical resection. Images were analyzed both visually and (semi)quantitatively by deriving the maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR). TBR was defined as the ratio between SUVmax of the primary tumor divided by SUVmax of the aortic blood pool. Finally, tracer uptake on PET was correlated to tissue expression of PSMA in surgical specimens.ResultsOut of 17 PSMA PET/CT scans, 13 scans demonstrated positive PSMA tracer uptake, with a mean SUVmax of 5.0 ± 1.3. The suspected primary tumor was detectable (TBR ≥ 2) with a mean TBR of 3.3 ± 1.3. For histologically confirmed PDAC, mean SUVmax and mean TBR were 4.9 ± 1.2 and 3.3 ± 1.5, respectively. Although eight patients had histologically confirmed regional lymph node metastases and two patients had distant metastases, none of these metastases demonstrated 18F-PSMA uptake. There was no correlation between 18F-PSMA PET/CT SUVmax and tissue expression of PSMA in surgical specimens.Conclusions18F-PSMA PET/CT was able to detect several pancreaticobiliary cancers, including PDAC. However, uptake was generally low, not specific to PDAC and no tracer uptake was observed in lymph node or distant metastases. The added value of PSMA PET in this setting appears to be limited.Trial registrationThe trial is registered as PANSCAN-2 in the European Clinical Trials Database (EudraCT number: 2020–002185-14).Graphical

Sodium valproate enhances efficacy of NKG2D CAR-T cells against glioblastoma

Chimeric antigen receptor T-cell (CAR-T) therapies have shown promise in glioblastoma clinical studies, but responses remain inconsistent due to heterogeneous tumor antigen expression and immune evasion post-treatment. NKG2D CAR-T cells have demonstrated a favorable safety profile in patients with hematologic tumors, and showed robust antitumor efficacy in various xenograft models, including glioblastoma. However, malignant glioma cells evade immunological surveillance by reducing NKG2D ligands expression or cleavage. To enhance the effectiveness of NKG2D CAR-T therapy, we investigated the potential of combining NKG2D CAR-T with approved drugs that cross the blood-brain barrier and augment NKG2D ligands expression in glioma cells. We found that sodium valproate (VPA), an antiepileptic drug, significantly increased surface NKG2D ligands expression on glioblastoma cells at a sublethal concentration. VPA treatment enhanced the susceptibility of glioblastoma cells to NKG2D CAR-T mediated cytotoxicity in both 2D monolayer and 3D tumor spheroid models in vitro. Moreover, VPA-treated glioblastoma cells stimulated CAR-T cells to produce higher levels of inflammatory cytokines (IL-2, IFN-γ, and IL-6). Mechanistically, VPA upregulated NKG2D ligands expression via the PI3K/Akt signaling pathway. Additionally, VPA treatment augmented the antitumor activity of NKG2D CAR-T cells in a glioblastoma xenograft model in vivo. These preclinical results suggest that combining VPA with NKG2D CAR-T therapy represents a promising strategy for improving glioblastoma treatment, warranting further clinical investigation.

Fluorescence Lifetime Endoscopy with a Nanosecond Time-Gated CAPS Camera with IRF-Free Deep Learning Method

Fluorescence imaging has been widely used in fields like (pre)clinical imaging and other domains. With advancements in imaging technology and new fluorescent labels, fluorescence lifetime imaging is gradually gaining recognition. Our research department is developing the tauCAMTM, based on the Current-Assisted Photonic Sampler, to achieve real-time fluorescence lifetime imaging in the NIR (700–900 nm) region. Incorporating fluorescence lifetime into endoscopy could further improve the differentiation of malignant and benign cells based on their distinct lifetimes. In this work, the capabilities of an endoscopic lifetime imaging system are demonstrated using a rigid endoscope involving various phantoms and an IRF-free deep learning-based method with only 6-time points. The results show that this application’s fluorescence lifetime image has better lifetime uniformity and precision with 6-time points than the conventional methods.