Reprogramming of lipid metabolism has emerged as a significant characteristic of malignancy during tumor development. Research indicates a critical link between lipid metabolism and the tumor immune microenvironment. This relationship not only facilitates cancer progression by remodeling the tumor microenvironment but also influences the functionality of immune cells. Alterations in lipid metabolism regulate the function and status of immune cells within the microenvironment, impacting immune evasion and the therapeutic efficacy of tumors. Consequently, targeting lipid metabolism is a viable strategy for intervening in tumorigenesis and tumor development. This review examines the roles of key lipid molecules, such as fatty acids and cholesterol, within the tumor microenvironment, highlighting how aberrant lipid metabolism can alter immune cell function. By investigating the interactions between lipid metabolism and immune cells in this setting, the review offers novel insights into early diagnosis, screening, and immunotherapy of malignant tumors. Furthermore, lipid metabolic reprogramming may act as a biomarker for monitoring early immune escape from tumors and predicting therapeutic outcomes, thereby enhancing early diagnosis and personalized cancer treatment.

Large granular lymphocytic leukemias (LGLLs), including T-cell LGLL and natural kill (NK)-cell LGLL variants, are rare lymphoproliferative disorders characterized by the chronic proliferation of cytotoxic lymphocytes. Despite recent advancements, challenges remain in distinguishing these entities from one another and from related disorders, such as T-cell prolymphocytic leukemia, adult T-cell leukemia/lymphoma, Sézary syndrome, and aggressive NK-cell leukemia, owing to overlapping clinical and morphologic features. This article aims to review the role of molecular and immunophenotypic markers in guiding diagnosis and prognosis of LGLLs, with brief review of their clinical and morphologic features by synthesizing current advances in molecular pathogenesis, immunophenotypic profiling, and updated World Health Organization (WHO) classification criteria in order to enhance diagnostic precision, improve prognostic assessment, and inform personalized treatment strategies for these challenging disorders.

Literature was searched through Pubmed and the recently published 5th WHO classification criteria. Articles were reviewed and analyzed with emphasis on recent molecular and cytogenetic insights.

A total of 106 publications were reviewed, and the recent molecular insights—focusing on those concerning STAT3 mutations in T-cell LGLL and TET2 mutations in NK-cell LGLL which have refined diagnostic frameworks, though gaps persist in understanding their clinical relevance and variability.

By providing a comparative analysis of large granular lymphocytic leukemias and their differential diagnoses in cooperation of the current advances in molecular pathogenesis, immunophenotypic profiling, and updated WHO classification criteria, this work aimed to enhance diagnostic precision, improve prognostic assessment, and inform personalized treatment strategies for these challenging LGLLs.

Precision medicine involves tailoring an individual’s genes or proteins to prevent, diagnose, or treat diseases such as cancer. Given the recent advances in cancer immunotherapy, there is now a focus on developing vaccines as a new treatment modality. Therapeutic vaccines for cancer are a precision medicine approach that has made enormous progress in recent years due to advances in vaccine engineering. This technology uses antigens derived from the patient’s tumor to create vaccines that are unique and specific to that patient. Although challenges remain, significant progress has been made in recent years, largely due to the advent of mRNA vaccines. This mini-review primarily focuses on developments in vaccine engineering, outstanding therapeutic obstacles, and recent human clinical trials.

Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. It is categorized into distinct pathological and clinical subtypes, including localized unicentric CD, idiopathic multicentric CD, and human herpesvirus 8-associated or human herpesvirus 8-negative variants. Diagnosing CD requires adherence to internationally recognized guidelines that integrate clinical, laboratory, and histological findings. However, distinguishing CD from other diseases can be complex, as numerous benign and malignant conditions can mimic its features. Additionally, individuals diagnosed with CD are at an elevated risk of developing various malignancies. In this article, we reviewed benign and malignant conditions that can mimic CD.

Literature search is conducted and reviewed.

Mimickers of CD include follicular hyperplasia, indolent B-cell lymphoproliferative disorders, peripheral T-cell malignancies, classic Hodgkin lymphoma, follicular dendritic cell tumors, plasma cell disorders, immunoglobulin G4 -related lymphadenopathy, autoimmune-associated lymphadenopathy, infectious causes of lymphadenopathy, and systemic syndromes like POEMS and TAFRO. Various malignancies are associated with CD, including plasma cell proliferations, lymphomas, follicular dendritic cell neoplasms, and Kaposi sarcoma.

This review explores the differential diagnoses and neoplasms linked to CD, emphasizing their role in accurate classification, treatment decisions, and patient management. A comprehensive understanding of CD and its mimickers is crucial for ensuring accurate diagnosis and appropriate patient management in clinical practice.

Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Epigenetic mechanisms have revealed that noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in HCC progression. This study aimed to construct a circRNA-miRNA-mRNA network in HCC and validate one axis within the network.

HCC-related transcriptome data were obtained from the Gene Expression Omnibus, and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs. The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted. The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.

We identified six differentially expressed circRNAs in HCC, which were linked to 13 miRNAs and 88 mRNAs. A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed. Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression, possibly through the miR-140-3p/KRAS axis. Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.

The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.

Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected patient with potential tenofovir resistance who required combined lamivudine and tenofovir therapy to achieve adequate viral suppression. The patient’s viral load (plasma) was monitored using the cobas® hepatitis B virus Test on the cobas® 6800 system. Hepatitis B antiviral drug resistance (AVDR) mutations were assessed by amplicon-based sequencing. Plasma was extracted using the MagNa Pure 24 system, and polymerase chain reaction targeting the polymerase gene (860bp) was performed. Sequencing was conducted on GridION R10.4.1 flow cells, and the resulting FASTQ files were analyzed using DeepChek®-HBV Software. We describe a female patient in her 60s with chronic hepatitis B who was e-antigen positive. She met treatment criteria in May 2020, when her alanine transaminase levels were 1.5 times above the upper limit of normal. She was initially started on entecavir but had to switch to tenofovir alafenamide in June 2020 due to a rash. Despite three years of tenofovir therapy, her viral load remained unsuppressed. AVDR testing identified two suspected tenofovir resistance mutations (V191I and A317S). Since no mutations associated with lamivudine resistance were detected, the patient was treated with a combination of lamivudine and tenofovir, achieving viral suppression after four months. Although rare, tenofovir resistance should be considered in patients with persistent viremia despite long-term therapy. AVDR sequencing facilitated the detection of potential tenofovir resistance and guided treatment decisions, leading to successful viral suppression in this case.

The role of radiosurgery in the treatment of grade 2 meningioma remains unclear. This study aimed to evaluate the long-term outcomes of gamma knife radiosurgery (GKRS) in patients with grade 2 meningiomas and to identify factors influencing tumor control and survival.

In this retrospective study, seventy patients underwent GKRS for grade 2 meningioma between 2007 and 2016. Tumor recurrence was categorized as local, marginal, or distant. Survival curves were estimated using the Kaplan-Meier method, while the log-rank test and Cox proportional hazards model were employed to analyze potential risk factors.

The median follow-up period was 48 months (range: 8 to 132 months). The one-year, three-year, and five-year local control rates were 92%, 73%, and 65%, respectively. The one-, three-, and three-year progression-free survival rates were 87%, 51%, and 44%, respectively. Multiple lesions and multiple prior recurrences were identified as negative predictors of marginal control and progression-free survival. Similarly, multiple lesions and marginal doses ≤13 Gy were associated with poor local control. Serious complications related to gamma knife use occurred in 4% of patients.

Our results support that GKRS is a reasonable treatment option in the management of grade 2 meningiomas. However, outfield progression remains a significant challenge, particularly in patients with multiple prior relapses and/or multiple lesions. More aggressive treatment strategies should be explored for these high-risk patients.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation. The presence of microRNAs (miRNAs) in plasma extracellular vesicles (EVs) presents a noninvasive approach to assess the molecular signatures of the disease. In this study, we aimed to identify miRNA biomarkers to distinguish molecular signatures of the liver disease associated with AATD in AATD individuals.

Using small RNA sequencing and qPCR, we examined plasma EV miRNAs in healthy controls (n = 20) and AATD patients (n = 17). We compared the EV miRNAs of AATD individuals with and without liver disease, developing an approach for detecting liver disease. A set of miRNAs identified in the AATD testing cohort was validated in a separate cohort of AATD patients (n = 45).

We identified differential expression of 178 EV miRNAs in the plasma of the AATD testing cohort compared to controls. We categorized AATD individuals into those with and without liver disease, identifying 39 differentially expressed miRNAs. Six miRNAs were selected to test their ability to discriminate liver disease in AATD. These were validated for their specificity and sensitivity in an independent cohort of 45 AATD individuals. Our logistic model established composite scores with three- and four-miRNA combinations, achieving areas under the curve of 0.737 and 0.751, respectively, for predicting AATD liver disease.

We introduce plasma EV-derived miRNAs as potential biomarkers for evaluating AATD liver disease. Plasma EV-associated miRNAs may represent a molecular signature of AATD liver disease and could serve as valuable tools for its detection and monitoring.