Real-world data for lenalidomide maintenance in responding patients of diffuse large B-cell lymphoma.

BACKGROUND: Approximately 40% patients of diffuse large B-cell lymphoma (DLBCL) would develop disease recurrence/progression after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy, with highly poor prognosis. An effective strategy to prolong the survival of this patient population is the additional single-drug maintenance therapy. lenalidomide, an immunomodulatory drug with oral activity, has direct anti-tumor activity and indirect effects mediated by multiple immune cells in the tumor microenvironment, such as B, T, natural killer (NK), and dendritic cells. Combining its controllable toxicity, it is promising in long-term maintenance therapy. This study aims at evaluating the clinical effect of lenalidomide maintenance therapy in responding DLBCL patients with R-CHOP treatment. METHODS: This retrospective study was devised in DLBCL cases who obtained complete response (CR) or partial response (PR) following 6-8 cycles of R-CHOP treatment between January 1, 2015 and July 31, 2019. Patients (n = 141) included were respectively assigned to receive lenalidomide maintenance treatment (lenalidomide, n = 50) and drug-free maintenance treatment (control, n = 91) after CR/PR. lenalidomide was provided orally at 25 mg/day for 10 days, with a cycle of 21 days and a treatment course of 2 years. Progression-free survival (PFS) was taken as the primary outcome. RESULTS: Of the total 141 subjects, the median follow-up time was 30.9 months (range, 5.7-68.9 months). The 2-year PFS was 84% (95% CI: 74%-94%) in the lenalidomide group and 53% (95% CI: 43%-63%) in the control group. The median PFS of the lenalidomide group was not reached, and that of the control group was 42.9 months (HR = 0.32; 95% CI: 0.16-0.63; p = 0.001). No remarkable difference in overall survival (OS) between the two groups was indicated (HR = 0.42; 95% CI: 0.16-1.12; p = 0.08). Central nervous system (CNS) recurrence happened in 5 patients (5.5%) of the control group, while none of the patients with lenalidomide had CNS recurrence. Additionally, neutropenia and cutaneous reactions were the most common Grade 1-2 adverse reactions after lenalidomide treatment, and neutropenia was the most frequent Grade 3-4 adverse reaction. CONCLUSION: Two-year lenalidomide maintenance treatment can significantly prolong the PFS of DLBCL patients who obtained CR/PR to first-line R-CHOP treatment.

Comprehensive Analysis of the Association between Human Diseases and Water Pollutants.

Drinking water is an important natural resource. For many people worldwide, especially in developing countries, access to safe drinking water is still a dream. An increasing number of human activities and industrialization have caused various physical, chemical, and biological pollutants to enter water bodies, affecting human health. Water pollutants contain a vast number of additives, such as perfluorinated chemicals, polybrominated diphenyl ethers, phthalate, nanomaterials, insecticides, microcystins, heavy metals, and pharmacologies. In this work, we aim to explore the potential relationship between water pollutants and human diseases. Here, we explored an integrative approach to identify genes, biological processes, molecular functions, and diseases linked to exposure to these water pollutants. These processes and functions affected by water pollutants are related to many diseases, including colonic neoplasms, breast neoplasms, hepatitis B, bladder cancer, and human cytomegalovirus infection. In addition, further analysis revealed the genes that play a key role in the human diseases induced by water pollutants. Therefore, conducting an integrative toxicogenomic analysis of water pollutants is more appropriate for evaluating the potential effects of water pollutants on human health.

Identifying tumor antigens and immune subtypes of gastrointestinal MALT lymphoma for immunotherapy development.

MALT lymphoma is an extranodal B-cell lymphoma of the marginal zone of mucosa-associated lymphoid tissue (MALT), caused by malignant transformation of B-cells in the marginal zone. In this work, we aim to explore the potential relationship between MALT lymphoma and DLBCL. Vaccines derived from messenger ribonucleic acid (mRNA) may provide satisfactory results. Despite being a promising treatment option, immunotherapy isn't widely used in treating renal cell carcinoma, as only a few patients respond to the treatment. The Cancer Genome Atlas (TCGA) analysis revealed gene expression profiles and clinical information. Antigen-presenting cells infiltrated the immune system using TIMER tool (http://timer.cistrome.org/). GDSC (Genomics of Drug Sensitivity in Cancer) data were used to estimate drug sensitivity. Immune-related genes were associated with a better prognosis in MALT lymphoma patients and higher levels of antigen-presenting cells. There is a significant relationship between these immune subtypes and immunological checkpoints, immunogenic cell death regulators, and prognostic variables for MALT lymphoma patients. In this study, we provide a theoretical foundation for the development of mRNA vaccines and suggest that KLHL14 could potentially be used as antigens to develop mRNA vaccines for MALT lymphoma.

The "m6A writer" METTL3 and the "m6A reader" IGF2BP2 regulate cutaneous T-cell lymphomas progression via CDKN2A.

It has been established that Cutaneous T-Cell lymphomas (CTCL) are caused by the monoclonal proliferation of T lymphocytes in the skin. This heterogeneous group of diseases represents a significant source of distress to patients since the diagnosis and treatment are often challenging. As one of the most abundant internal modifications in mRNA in higher eukaryotes, N6-methyladenosine (m6A) is widely recognized to affect the development and progression of cancers. However, knowledge on the involvement of m6A in CTCL is still limited. In this work, we revealed the role of METTL3-mediated m6A modification in CTCL progression. ELISA, western blot, and qRT-PCR assays demonstrated that METTL3 was significantly downregulated in CTCL cells both in vivo and in vitro. CCK-8, EdU, flow cytometry, and transwell assays showed that the decline in METTL3 levels was responsible for CTCL cell proliferation and migration. Furthermore, using small interfering RNAs against METTL3 and the RIP assay, we showed that CDKN2A was a key regulator during this process in vitro and in vivo, and insufficient methylation modification blocked the interaction between CDKN2A and m6A reader IGF2BP2, resulting in mRNA degradation. To the best of our knowledge, this is the first study to depict the role of m6A in CTCL development and provide potential bio-targets for therapy.

The comprehensive analysis based study of perfluorinated compounds-Environmental explanation of bladder cancer progression.

Perfluorinated compounds are emerging organic pollutants widely used in building materials, textiles, and electric equipment. Herein, silico analysis was conducted using bioinformatics approach to assess the potential relationship between bladder cancer and perfluorinated compounds. Transcriptome profiles and data of perfluorinated compounds were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression and Comparative Toxicogenomics databases. Gene Ontology (GO9 and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that interactive genes were mainly enriched in bladder cancer (BC). Transcriptome profiles were used to verify the expression of m6A-related genes at the mRNA and protein levels. Most m6A-related genes predicted BC prognosis. Survival analysis and ROC curves demonstrated that the expression levels of m6A-related genes were associated with BC prognosis. Perfluorooctanoic acid (PFOA) significantly increased the cell proliferation ability and promoted cell invasion capacity. In addition, PFOA significantly increased the cell viability and cell invasion capacity of T24 and BIU-87 cell lines compared with the control group. Taken together, these results show that perfluorinated compounds could promote BC progression. DATA AVAILABILITY: Data and materials are available within the manuscript.