Malignant Research Articles

Fibrin-Associated Large B-Cell Lymphoma in a Young Patient in the Setting of Pleural Effusion

Abstract Introduction/Objective Fibrin-associated large B-cell lymphoma (FA-LBCL) is a proliferation of EBV-positive large B- cells in association with fibrinous debris, typically in the context of prostheses, hematomas, pseudocysts and myxomas. It is a newly described entity and is extremely rare, with no deaths reported as a direct result. It is indolent and not visible on imaging, instead being found incidentally on microscopy. It is mainly a diagnosis of exclusion and is characterized by sheets of neoplastic lymphocytes contained within a fibrin background. The median age of presentation is 55, with 75% of cases being reported among elderly patients. The prognosis is excellent and surgery is considered curative. It needs to be distinguished from malignant lymphomas, mainly diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI), which is also EBV-positive but occurs in elderly patients with a longstanding history of inflammation. The two have identical immunohistochemical profiles but vastly different clinical presentations and outcomes. Methods/Case Report A 35-year-old male with end-stage renal disease and a history of recurrent pleural effusions presented with dyspnea. CT showed a large loculated right-sided pleural effusion with no lymphadenopathy. Pleural fluid cytology was negative for any malignant cells. He underwent decortication to relieve pleural rind constriction. Microscopy revealed small layers of fibrin with an infiltrate of atypical, EBV-positive B-cells with a Ki-67 index of 60%. As the morphological findings and clinical presentation did not fit other known lymphomas, the case was signed out as FA-LBCL. The patient has followed up with oncology and PET scans have been negative for any malignancy. He is currently on the waiting list for a renal transplant. Results (if a Case Study enter NA) NA Conclusion FA-LBCL is a rare benign neoplasm, identified incidentally and cured by surgical resection. It is mainly diagnosed in the elderly, but the number of cases is limited and the age distribution may be skewed. This case involved a much younger patient and is the first known diagnosis in the pleural setting. It is important to differentiate this entity from DLBCL-CI, which is aggressive and requires intense oncological treatment. In addition, patients with FA-LBCL can undergo immediate solid organ transplantation, whereas those with DLBCL-CI need to be in remission for at least three years before receiving a transplant.

Case Report: Aspirated Airway Foreign Body Mimicking Endobronchial Mass: A Diagnostic Challenge

Abstract Introduction/Objective Despite advancements in imaging modalities, identifying retained foreign bodies within the lung remains arduous. Detecting small foreign bodies is crucial as they can serve as a focal point for subsequent infections. Initial assessments may mimic malignancy. Herein, we present a case of a retained foreign body masquerading as an endobronchial mass, accompanied by unilateral pleural effusion and persistent hypoxia. Subsequent bronchoscopy showed a pearly white endobronchial mass partially obstructing the segmental bronchus at the posterior basal segment of the right lower lobe of lung with accompanying right pleural effusion and atelectasis. Methods/Case Report This is a 58-year-old male with history of hypertension, deep vein thrombosis, transient ischemic attack, and a recent motor vehicle accident with blunt chest trauma. He had a thoracic spinal cord transection with grade III blunt thoracic aortic injury, developed anasarca, hypoxia, right pleural fluid requiring multiple thoracentesis, and right sided hemothorax requiring massive transfusion protocol. Subsequent evaluations, including bronchoscopic transbronchial forceps biopsies and bronchial wash and pleural fluid cytologic examinations showed no malignant cells. Repeat bronchoscopy was concerning for enlarging mass and obstruction. Bronchoscopy almost 2 months after MVA revealed an endobronchial foreign body (tooth) lodged in the left lower lobe of lung posterior segment. Results (if a Case Study enter NA) N/A Conclusion While aspiration of foreign bodies into the tracheobronchial tree is not uncommon especially in children, foreign bodies, particularly teeth, are rare in adults. Bronchial foreign body aspiration may occur in trauma, with diagnosis typically relying on history and physical examination. Detection remains challenging despite imaging advancements, with implications including infection nidus formation. In our case, delayed diagnosis highlights the importance of considering unusual etiologies in persistent pulmonary pathology. Retrospective imaging analysis and CT findings suggested a foreign body, emphasizing the utility of imaging in suspected cases. Prompt surgical intervention is crucial to prevent complications such as recurrent infections.

Metastatic Carcinosarcoma with a Sarcomatous Predominance?

Abstract Introduction/Objective Uterine carcinosarcoma (CS), also known as Malignant Mixed Müllerian Tumor, is a malignancy characterized by mixed epithelial and mesenchymal components. It is rare and aggressive, most frequently occurring in elderly, postmenopausal women with a median age of 65 years. CS has a tendency to metastasize with an overall poor prognosis. Fine needle aspiration can be useful in identifying metastatic disease, however, demonstration of both sarcomatous and carcinomatous components can be difficult. Methods/Case Report Our patient is a 68 year old female who was first diagnosed with endometrial carcinosarcoma on an endometrial biopsy in 2022. She subsequently underwent a total abdominal hysterectomy with radical dissection, bilateral salpingo-oophorectomy, upper vaginectomy, sentinel lymph node dissection as well as chemotherapy. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 all showed intact nuclear expression. Remission was achieved for about a year, after which she was found to have a moderate right sided pleural effusion with right lower lung infiltrates. Also, a right upper lobe mass was reported on chest CT scan. Paracentesis was performed and cytology was consistent with predominantly atypical spindle cells accompanied by a mixed inflammatory infiltrate. Immunohistochemical stains were performed on the cell block, tumor cells were positive for smooth muscle actin, vimentin and negative for desmin, S-100, SOX-10, CD34, P63, TTF-1 and pancytokeratin. Cytology diagnosis was rendered as malignant cells present, consistent with metastatic CS. A subsequent lung mass core biopsy also confirmed the diagnosis. Results (if a Case Study enter NA) NA Conclusion The cytomorphological features in effusion samples from metastatic CS have the carcinomatous component readily identifiable, and only a minority of effusion samples show additional sarcomatous component. The exact diagnosis of CS may not be possible due to the absence of sarcomatous components. Alternatively, as we present in this rare case of metastatic CS, the sarcomatous component in the form of abundant atypical oval to spindle cells with hyperchromatic nuclei may be the only form of malignant cells present in the specimen. Careful morphological assessment of architectural patterns, a good past medical history, availability of cell blocks and immunohistochemistry are vital in providing an accurate diagnosis in such rare cases of metastatic CS.

Unraveling the metastasis-preventing effect of miR-200c in vitro and in vivo.

Advanced breast cancer, as well as ineffective treatments leading to surviving cancer cells, can result in the dissemination of these malignant cells from the primary tumor to distant organs. Recent research has shown that microRNA 200c (miR-200c) can hamper certain steps of the invasion-metastasis cascade. However, it is still unclear whether miR-200c expression alone is sufficient to prevent breast cancer cells from metastasis formation. Hence, we performed a xenograft mouse experiment with inducible miR-200c expression in MDA-MB 231 cells. The ex vivo analysis of metastatic sites in a multitude of organs, including lung, liver, brain, and spleen, revealed a dramatically reduced metastatic burden in mice with miR-200c-expressing tumors. A fundamental prerequisite for metastasis formation is the motility of cancer cells and, therefore, their migration. Consequently, we analyzed the effect of miR-200c on collective- and single-cell migration in vitro, utilizing MDA-MB 231 and MCF7 cell systems with genetically modified miR-200c expression. Analysis of collective-cell migration revealed confluence-dependent motility of cells with altered miR-200c expression. Additionally, scratch assays showed an enhanced predisposition of miR-200c-negative cells to leave cell clusters. The in-between stage of collective- and single-cell migration was validated using transwell assays, which showed reduced migration of miR-200c-positive cells. Finally, to measure migration at the single-cell level, a novel assay on dumbbell-shaped micropatterns was performed, which revealed that miR-200c critically determines confined cell motility. All of these results demonstrate that sole expression of miR-200c impedes metastasis formation in vivo and migration in vitro and highlights miR-200c as a metastasis suppressor in breast cancer.

The Importance of Recognizing Vaginal Melanoma, A Unique and Aggressive Subtype of Mucosal Melanoma with Undefined Staging and Treatment Protocols: Case Report and Literature Review

Abstract Introduction/Objective Primary vaginal melanoma is a highly aggressive subtype of mucosal melanoma, with few cases reported in the literature. Mucosal melanomas represent a very small subset of melanoma cases, with even fewer found in the vagina. There is a frequent delay in diagnosis due to absent or nonspecific symptoms. Methods/Case Report We report two cases of primary vaginal melanoma that were found on biopsy due to abnormal postmenopausal bleeding. Case 1 is a 62-year-old woman that was found to have a necrotic mass originating from the vaginal apex, while case 2 is a 66-year-old woman that had a vaginal polyp. Microscopic examination of both cases revealed sheets of malignant cells with prominent nucleoli, brisk mitotic activity, and patchy melanin pigment. Immunohistochemical stains for MART-1 and SOX10 were positive in both cases, supporting the diagnosis. The patient in case 1 had an upper vaginectomy and is currently on immunotherapy as part of a clinical trial. Further treatment and status of the patient in case 2 is unknown. Results (if a Case Study enter NA) N/A Conclusion Due to the rarity of cases, little is known about the etiology and risk factors. A standardized staging system is not yet accepted, with most using a combination of the AJCC and FIGO systems, however, neither are specific for vaginal melanomas. Patients are often metastatic at the time of diagnosis due to delayed diagnosis and aggressive nature of the disease. Specific treatment protocols have not yet been defined, and it is debated whether a more conservative or aggressive approach is favored. The disease control and survival rates are dismal with a poor prognosis. The role of adjuvant and targeted molecular therapies is still being investigated. The addition of our cases to the literature will hopefully bring more awareness to vaginal melanoma as a diagnostic possibility and encourage more research to be done.

Mammary Carcinoma Metastasizing to Renal Cell Carcinoma: A Case Report

Abstract Introduction/Objective The simultaneous occurrence of multiple primary cancers is rare, and even rarer is the phenomenon of one cancer metastasizing to another. Here, we present a case of mammary carcinoma and renal cell carcinoma diagnosed concurrently yet presenting as a cancer-to-cancer metastasis. Methods/Case Report A 79-year-old woman, with a 2-week duration of apnea and cough, was found to have right pleural effusion and underwent thoracocentesis. Cytological examination of the fluid revealed malignant cells suggestive of adenocarcinoma. CT abdomen and chest revealed a 1.6 cm right breast nodule, 4.4 cm right axillary mass and right renal lesions measuring 3.0 and 1.6 cm. Core biopsy of the renal lesion showed two populations of cells. One population exhibited moderate cytoplasm and enlarged nuclei displaying anisonucleosis and hyperchromasia arranged singly as well as in sheets and clusters. These cells stained positive for GATA 3, ER, mammaglobin and CK7. Intermixed, were the second population of cells with clear cytoplasm and low nuclear grade forming sheets and replacing renal tissue. These cells were positive for CA9, CD10 and PAX 8 but negative for P40. Based on these findings a diagnosis of low-grade renal carcinoma of clear cell type with a metastatic carcinoma of mammary origin was established. Results (if a Case Study enter NA) NA Conclusion Renal cell carcinoma and breast carcinoma are known to increase the occurrence of each other. When breast and renal lesions are identified concurrently, the possibility of breast metastasis should be strongly considered. However, the concurrent appearance of renal cell carcinoma harboring metastatic breast cancer is extremely rare.This contributes valuable insights into the complex interplay between different cancer types. Understanding these rare phenomena can aid in refining diagnostic approaches and treatment strategies.

Improving the Utility of a Cancer Gene Mutation Panel for Multiple Myeloma Patients

Abstract Multiple myeloma is a plasma cell malignancy that accounts for 1-2% of all cancer diagnoses and 10-15% of hematopoietic neoplasms. Clonal rearrangement of the IG locus suggests a monoclonal model for pathogenesis. The presence of cytogenetic abnormalities in >90% of cases suggests transformation by chromosomal instability and rearrangement. Classification and consensus guidelines by The International Myeloma Working Group (IMWG) and others reflect this by categorizing myeloma based on ploidy, translocations, and chromosomal abnormalities. Interestingly, a portion of Emory’s test volume for cancer gene mutation profiling by second generation short-read sequencing is for multiple myeloma cases. This suggests our 75-gene myeloid neoplasm panel (MMP75) is being utilized for medical purposes that are not met by cytogenetic and microarray characterizations performed during the diagnostic workup of multiple myeloma. Inspired by this observation, this study investigates providers motivations for ordering MMP75 and assesses the adequacy of our current implementation for their stated purposes. Anecdotes from ordering physicians indicate interest in MMP75 results when informing prognosis, selecting treatments, and evaluating for treatment associated secondary neoplasms. A more formal survey is underway that will statistically capture how the results of MMP75 testing were ultimately used: to inform diagnosis, determine prognosis, guide treatment, explain progression, identify/rule-out secondary neoplasia, or no effect on management. We also explore the variants called by MMP75 when performed using bone marrow from patients who received a cytogenetic workup for multiple myeloma at some point. A retrospective analysis of the 5-year interval between Jan 2019 and Jan 2024 identified 156 cases meeting this criterion. The number of pathogenic variants per case ranged between 1 and 8, with mutations detected across 42 genes. The genes most frequently identified with pathogenic mutations were TP53 (22.4%), DNMT3A (19.2%), TET2 (14.7%), and ASXL1 (12.2%). All four have been associated with adverse outcomes in patients with multiple myeloma. Activating events in therapeutic targets included mutations in the RAS/RAF pathway (16.7%), JAK/STAT signaling (2.6%), and the kinase KIT (0.6%). While these findings support the use of MMP75 for detection of relevant mutations, the genetic variants identified are not unique to multiple myeloma. Mutations detected in DNMT3A, TET2, and ASXL1 are common in clonal hematopoiesis of indeterminant potential (CHIP) and myeloid neoplasms. Hotspot mutations in TP53 and activating events in the RAS/RAF pathway also occur in various hematologic malignancies. This test therefore detects events that occur in both the plasma cell compartment and other cells of origin. This encumbers distinguishing variants that inform on a patient’s multiple myeloma from events that suggest a secondary neoplasm. Future directions include determining whether the effect of plasma cell enrichment on a mutations variant allele frequency (VAF) in repeat testing can help distinguish true multiple myeloma variants from events in other cells.

AKR1B1-dependent fructose metabolism enhances malignancy of cancer cells.

Fructose metabolism has emerged as a significant contributor to cancer cell proliferation, yet the underlying mechanisms and sources of fructose for cancer cells remain incompletely understood. In this study, we demonstrate that cancer cells can convert glucose into fructose through a process called the AKR1B1-mediated polyol pathway. Inhibiting the endogenous production of fructose through AKR1B1 deletion dramatically suppressed glycolysis, resulting in reduced cancer cell migration, inhibited growth, and the induction of apoptosis and cell cycle arrest. Conversely, the acceleration of endogenous fructose through AKR1B1 overexpression has been shown to significantly enhance cancer cell proliferation and migration with increased S cell cycle progression. Our findings highlight the crucial role of endogenous fructose in cancer cell malignancy and support the need for further investigation into AKR1B1 as a potential cancer therapeutic target.

AML-VAC-XS15-01: protocol of a first-in-human clinical trial to evaluate the safety, tolerability and preliminary efficacy of a multi-peptide vaccine based on leukemia stem cell antigens in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) has a dismal prognosis, mostly due to minimal residual disease-driven relapse, making an elimination of persisting therapy-resistant leukemia progenitor/stem cells (LPCs) the main goal for novel therapies. Peptide-based immunotherapy offers a low-side-effect approach aiming to induce T cell responses directed against human leukocyte antigen (HLA) presented tumor antigens on malignant cells by therapeutic vaccination. Mass spectrometry-based analysis of the naturally presented immunopeptidome of primary enriched LPC and AML samples enabled the selection of antigens exclusively expressed on LPC/AML cells, which showed de novo induction and spontaneous memory T cell responses in AML patients, and whose presentation and memory T cell recognition was associated with improved disease outcome. Based on these data the therapeutic vaccine AML-VAC-XS15 was designed, comprising two mutated HLA class I-restricted peptides from the common AML-specific mutation in NPM1 and seven HLA class II-restricted peptides (six non-mutated high-frequent AML/LPC-associated antigens and one mutated peptide from the AML-specific mutation R140Q in IDH2), adjuvanted with the toll like receptor 1/2 ligand XS15 and emulsified in Montanide ISA 51 VG. A phase I open label clinical trial investigating AML-VAC-XS15 was designed, recruiting AML patients in complete cytological remission (CR) or CR with incomplete blood count recovery. Patients are vaccinated twice with a six-week interval, with an optional booster vaccination four months after 2nd vaccination, and are then followed up for two years. The trial's primary objectives are the assessment of the vaccine's immunogenicity, safety and toxicity, secondary objectives include characterization of vaccine-induced T cell responses and assessment of preliminary clinical efficacy. The AML-VAC-XS15-01 study was approved by the Ethics Committee of the Bavarian State medical association and the Paul-Ehrlich Institut (P01392). Clinical trial results will be published in peer-reviewed journals.

Method for co-registration of high-resolution specimen PET-CT with histopathology to improve insight into radiotracer distributions

BackgroundAs the spatial resolution of positron emission tomography (PET) scanners improves, understanding of radiotracer distributions in tissues at high resolutions is important. Hence, we propose a method for co-registration of high-resolution ex vivo specimen PET images, combined with computed tomography (CT) images, and the corresponding specimen histopathology.MethodsWe applied our co-registration method to breast cancer (BCa) specimens of patients who were preoperatively injected with 0.8 MBq/kg [18\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{18}$$\\end{document}F]fluorodeoxyglucose ([18F]FDG). The method has two components. First, we used an image acquisition scheme that minimises and tracks tissue deformation: (1) We acquired sub-millimetre (micro)-PET-CT images of ±2 mm-thick lamellas of the fresh specimens, enclosed in tissue cassettes. (2) We acquired micro-CT images of the same lamellas after formalin fixation to visualise tissue deformation. (3) We obtained 1 hematoxylin and eosin (H&E) stained histopathology section per lamella of which we captured a digital whole slide image (WSI). Second, we developed an automatic co-registration algorithm to improve the alignment between the micro-PET-CT images and WSIs, guided by the micro-CT of the fixated lamellas. To estimate the spatial co-registration error, we calculated the distance between corresponding microcalcifications in the micro-CTs and WSIs. The co-registered images allowed to study standardised uptake values (SUVs) of different breast tissues, as identified on the WSIs by a pathologist.ResultsWe imaged 22 BCa specimens, 13 cases of invasive carcinoma of no special type (NST), 6 of invasive lobular carcinoma (ILC), and 3 of ductal carcinoma in situ (DCIS). While the cassette framework minimised tissue deformation, the best alignment between the micro-PET-CT images and WSIs was achieved after deformable co-registration. We found an overall average co-registration error of 0.74 ± 0.17 mm between the micro-PET images and WSIs. (Pre)malignant tissue (including NST, ILC, and DCIS) generally showed higher SUVs than healthy tissue (including healthy glandular, connective, and adipose tissue). As expected, inflamed tissue and skin also showed high uptake.ConclusionsWe developed a method to co-register micro-PET-CT images of surgical specimens and WSIs with an accuracy comparable to the spatial resolution of the micro-PET images. While currently, we only applied this method to BCa specimens, we believe this method is applicable to a wide range of specimens and radiotracers, providing insight into distributions of (new) radiotracers in human malignancies at a sub-millimetre resolution.

Results of Pap Smear in Females Who are Actively Reproducing in Outlying Medical Centers at Parachinar

Objective: To ascertain the prevalence of different cervical abnormalities in connection t pap smear results with age distribution of patient.  Method The demographic makeup of the study population was deduced by calculating the percentages of patients in each age group. Numerous diseases were also identified using the results of the Pap smear test, and percentages associated with each diagnosis were computed. This methodology made it possible to thoroughly analyze the participants' diagnoses and age distribution, which revealed trends in cervical health. One hundred participants in all had Pap smears performed as part of the study. Four age groups were established based on the age distribution data gathered: 18–25, 25–35, 35–45, and 45–55 years old.  Result The majority of participants (37%) were found to be between the ages of 25 and 35, while there was a wide variation of participant ages overall. Pap smear tests are crucial for identifying potentially malignant or precancerous diseases, as evidenced by the majority of patients (71%) receiving a diagnosis of cancer or intraepithelial lesions. There was also representation from the following age groups: 18–25 (9%), 35–45 (28%), and 45–55 (4%). Four percent of the cases had atypical squamous cell lesions, two percent had low-grade squamous intraepithelial lesions, and one percent had high-grade lesions.  Conclusion These findings advance customized screening programs and therapies aimed at specific age groups and diagnostic categories as well as our knowledge of cervical health patterns. People who are fertile should definitely get screened for cervical cancer because the age group of 25 to 35 accounts for a substantial portion of diagnoses. The importance of Pap smear testing for early identification and preventive medicine is underscored by the prevalence of intraepithelial lesions or cancer.

Functional variant rs9344 at 11q13.3 regulates CCND1 expression in multiple myeloma with t(11;14).

Multiple myeloma (MM) is a plasma cell (PC) malignancy characterized by cytogenetic abnormalities, such as t(11;14)(q13;q32), resulting in CCND1 overexpression. The rs9344 G allele within CCND1 is the most significant susceptibility allele for t(11;14). Sequencing data from 2 independent cohorts, CoMMpass (n = 698) and Mayo Clinic (n = 661), confirm the positive association between the G allele and t(11;14). Among 80% of individuals heterozygous for rs9344 with t(11;14), the t(11;14) event occurs on the G allele, demonstrating a biological preference for the G allele in t(11;14). Within t(11;14), the G allele is associated with higher CCND1 expression and elevated H3K27ac and H3K4me3. CRISPR/Cas9 mediated A to G conversion resulted in increased H3K27ac over CCND1 and elevated CCND1 expression. ENCODE ChIP-seq data supported a PAX5 binding site within the enhancer region covering rs9344, showing preferential binding to the G allele. Overexpression of PAX5 resulted in increased CCND1 expression. These results support the importance of rs9344 G enhancer in increasing CCND1 expression in MM.

Pancancer analysis of NDUFA4L2 with focused role in tumor progression and metastasis of colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignant disease with a high mortality rate, and identification of novel prognostic biomarkers and therapeutic targets is urgently needed. Although NDUFA4L2 has high expressions in various tumors and affects tumor progression, its role in COAD remains unclear. The role of NDUFA4L2 in COAD was analyzed utilizing datasets available from public databases including The Cancer Genome Atlas, The Genotype-Tissue Expression (GTEx), Gene Expression Omnibus, Alabama Cancer Database (UALCAN), and The Human Protein Atlas databases. The prognostic value of NDUFA4L2 was determined using Kaplan-Meier analysis and Cox regression analysis. To investigate the possible mechanism underlying the role of NDUFA4L2 in COAD, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were employed. The correlation between NDUFA4L2 expression and immune cell infiltration levels was examined through single-sample gene set enrichment analysis (ssGSEA). The NDUFA4L2 expression levels in COAD patients and cell lines were validated through immunohistochemistry, immunofluorescence, qRT-PCR, and Western blot. Wound healing assay was also performed to evaluate the effect of NDUFA4L2 on COAD metastasis. Furthermore, the NDUFA4L2 mediated competing endogenous RNA (ceRNA) regulatory network was predicted and constructed through a variety of databases. The comprehensive pan-cancer analysis showed that NDUFA4L2 possesses diagnostic and prognostic value in many cancers, especially in COAD. GO-KEGG and GSEA analyses indicated that NDUFA4L2 was associated with multiple biological functions including epithelial-mesenchymal transition and adaptation to hypoxia. The ssGSEA analysis showed that NDUFA4L2 expression was associated with immune infiltration. In vitro experiments confirmed upregulation of NDUFA4L2 in COAD tissues and cell lines, and NDUFA4L2 overexpression significantly promoted migration of COAD cells. In addition, the C9orf139 /miR-194-3p axis was speculated as the possible upstream regulators of NDUFA4L2 in COAD. This study demonstrated that NDUFA4L2 upregulation was correlated with tumor progression, relapsed prognosis and aggressive migration of COAD, suggesting that NDUFA4L2 can act as an effective prognostic biomarker and a promising therapeutic target for COAD treatment.

Copper Nanoparticles Green-Formulated byCurcuma longa Extract Induce Apoptosis via P53 and STAT3 Signaling Pathways in Bladder Carcinoma Cell.

The study outlines the production of new copper nanoparticles infused with Curcuma longa extract to trigger apoptosis through P53 and signal transducer and activator of transcription 3 (STAT3) signaling pathways in bladder carcinoma cells. The structural characteristics of the nanoparticles that were synthesized were analyzed through various sophisticated methods such as transmission electron microscopy (TEM), field emission-scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), and Fourier transform infrared spectroscopy (FT-IR). During the antioxidant evaluation, the IC50 values for copper nanoparticles and butylated hydroxytoluene (BHT) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals were found to be 116µg/mL and 31µg/mL, respectively. The cells treated with copper nanoparticles underwent evaluation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for 48h to determine their anticancer properties on TCCSUP bladder carcinoma cell. The TCCSUP cell line exhibited an IC50 of 290µg/mL when exposed to copper nanoparticles. The viability of malignant cells decreased upon treatment with copper nanoparticles. Furthermore, the copper nanoparticles presence led to a 65-75% increase in cell apoptosis, along with an increase in Bax and cleaved caspase-8 and a decrease in the Bcl-2. Furthermore, the copper nanoparticles presence resulted in the suppression of colony formation. Notably, the molecular pathway analysis in cells treated with copper NPs demonstrated an increase in p53 expression, along with a decrease in the expression of both total and phosphorylated STAT3. This offers that p53 and STAT3 play a crucial role in the biological efficacies induced by the nanoparticles in human carcinoma cells. The data of our research suggest that copper NPs could have significant potential as an anticancer treatment for human bladder carcinoma cells.

Potential Player of Platelet in the Pathogenesis of Cardiotoxicity: Molecular Insight and Future Perspective.

Cancer patients may encounter the onset of cardiovascular disease due to tumor advancement or chemotherapy, commonly known as "cardiotoxicity." In this respect, the conventional chemotherapy treatment protocol involves a mixture of different medications. These medications can be detrimental to cardiac tissue, consequently exposing the patient to the possibility of irreversible cardiac injury. The enhancement of oxidative stress and inflammation is an important mechanism of chemotherapeutic agents for developing cardiotoxicity. Regarding their dual pro- and anti-inflammatory functions, platelets can significantly influence the progression or suppression of cardiotoxicity. Therefore, the expression of platelet activatory markers can serve as valuable prognostic indicators for cardiotoxicity. The primary objective of this study is to examine the significance of platelets in cardiotoxicity and explore potential strategies that could effectively target malignant cells while minimizing their cytotoxic impact, such as cardiotoxicity and thrombosis.

Identification of Phospholipids Relevant to Cancer Tissue Using Differential Ion Mobility Spectrometry

Phospholipids are the main building components of cell membranes and are also used for cell signaling and as energy storages. Cancer cells alter their lipid metabolism, which ultimately leads to an increase in phospholipids in cancer tissue. Surgical energy instruments use electrical or vibrational energy to heat tissues, which causes intra- and extracellular water to expand rapidly and degrade cell structures, bursting the cells, which causes the formation of a tissue aerosol or smoke depending on the amount of energy used. This gas phase analyte can then be analyzed via gas analysis methods. Differential mobility spectrometry (DMS) is a method that can be used to differentiate malignant tissue from benign tissues in real time via the analysis of surgical smoke produced by energy instruments. Previously, the DMS identification of cancer tissue was based on a ‘black box method’ by differentiating the 2D dispersion plots of samples. This study sets out to find datapoints from the DMS dispersion plots that represent relevant target molecules. We studied the ability of DMS to differentiate three subclasses of phospholipids (phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine) from a control sample using a bovine skeletal muscle matrix with a 5 mg addition of each phospholipid subclass to the sample matrix. We trained binary classifiers using linear discriminant analysis (LDA) and support vector machines (SVM) for sample classification. We were able to identify phosphatidylcholine, -inositol, and -ethanolamine with SVM binary classification accuracies of 91%, 73%, and 66% and with LDA binary classification accuracies of 82%, 74%, and 72%, respectively. Phosphatidylcholine was detected with a reliable classification accuracy, but ion separation setups should be adjusted in future studies to reliably detect other relevant phospholipids such as phosphatidylinositol and phosphatidylethanolamine and improve DMS as a microanalysis method and identify other phospholipids relevant to cancer tissue.

Emerging Role of CAR-T Therapy in Acute Myeloid Leukemia

Acute myeloid leukemia (AML), a malignant clonal disease originating from hematopoietic stem cells. In the past few decades, AML treatment has been dominated by a "3+7" regimen (anthracyclines + cytarabine), and the survival curve has stagnated. However, these procedures are associated with serious adverse effects. The development of chimeric antigen receptor (CAR)-T cell treatment provides a viable alternative, with decreased non-relapse death rates. Despite its potential, CAR-T cell therapy for AML confronts significant obstacles due to the disease's heterogeneity and accompanying toxicity. Genetic alteration strategies are being investigated to improve its safety and efficacy. Engineering CAR-T cells to express inhibitory receptors or suicide genes can help regulate T cell activity and prevent excessive immune activation. In summary, while CAR-T cell treatment has promise for AML, overcoming its hurdles through genetic modification and target refining is crucial. This review focuses on the existing landscape and future directions of CAR-T cell treatment for AML.

Research Progress on Photothermal Therapy of Malignant Tumor Cells

Malignant tumors, also known as cancer, are among the diseases with the highest incidence and mortality rates in the world. Photothermal therapy (PTT) involves injecting materials with high photothermal conversion efficiency (PTA) into the human body and using the principle of photothermal conversion to kill malignant tumor cells at the lesion site with high temperatures. This paper reviews various methods of photothermal therapy for malignant tumors, summarizes the basic therapeutic logic of photothermal therapy, and forecasts the future development prospects of this treatment method.

Predictors of Failed Outcomes in Ureteral Reconstruction: A Real-World Retrospective Study

Background and Objectives: Ureteral reconstruction is aimed at maintaining ureteral patency without the need for long-term catheters like ureteral stents or percutaneous nephrostomies. Different surgical strategies are adopted based on the etiology, the location of the injury, and the severity of the injury. We aimed to analyze the parameters that can predict which patients might not be free from further catheterization after reconstruction. Materials and Methods: This study included patients who underwent ureteral reconstruction from January 2007 to December 2021. The success of ureteral reconstruction was defined as being free from further catheterization after the operation. Results: A total of 184 patients underwent ureteral reconstruction. Malignant disease with ureteral invasion and iatrogenic injuries accounted for 79.9% of the cases. The majority (79.3%) did not have to undergo subsequent interventions. Predictors for a failed result of ureteral reconstruction included a history of radiotherapy (OR = 2.75, p = 0.01), chronic kidney disease (CKD) (OR = 3.42, p < 0.001), and an upper ureteric location of the injury (OR = 5.68, p = 0.042). Conclusions: A history of radiation therapy, an upper third ureteric location of the injury, and CKD were identified as predictors of a failed ureteral reconstruction. Malignant diseases, surgical methods, and repair techniques did not significantly affect the outcome of the operation.

Pharmaceutical Agents for Targeting Autophagy and Their Applications in Clinics

Autophagy is the process by which damaged regions of the cytoplasm and intracellular pathogens are degraded. This mechanism often serves an adaptive role in cells, enhancing their survival. It plays a direct or indirect role in the development of various pathological conditions within the body. This phenomenon is common in various malignant diseases, where autophagy is associated with the resistance of transformed cells to chemotherapy. Conversely, abnormal activation of autophagy can trigger cell death, a process often seen in neurodegenerative conditions. Given that dysregulation of autophagy is associated with the progression of numerous pathological conditions, this is of significant interest to the developers of drugs that can effectively modulate autophagy for both basic research and clinical applications. Here, we provide a brief description of the mechanism of macroautophagy, the most prevalent form of autophagy identified in humans. We also discuss the clinical potential of drugs that can modulate autophagy, highlighting their use in combating diseases associated with direct or indirect dysregulation of this essential process.