Antitumor effect of exopolysaccharide from Lactiplantibacillus plantarum WLPL09 on melanoma mice via regulating immunity and gut microbiota.

Exopolysaccharide (EPS-09) from L. plantarum WLPL09 was systemically investigated for the antitumor effect in B16F10 melanoma bearing mice model. The results showed that administraion of EPS-09 (200 mg/kg) could sigificantly inhibit the tumor growth of melanoma bearing mice, with a inhibition rate of 42.53 %. Meanwhile, compared to the Model group, high dose of EPS-09 (200 mg/kg) administraion could increase the spleen index (P = 0.10), promote the splenic lymphocytes proliferation under the stimulation of ConA and LPS with a proliferation rate of 120.58 % and 169.88 %, respectively, enhance the amount of CD4+ and CD8+ T cells (P < 0.0001, P = 0.0149) in tumor tissue, as well as the serum content of cytokines, i.e., TNF-α, IFN-γ, IL-2 (P < 0.05) and IL-6 (P = 0.039) of B16F10 melanoma bearing mice. The transcriptional level analysis revealed that EPS-09 (200 mg/kg) administraion could sigificantly (P < 0.05) upregulate the transcription of apoptosis raleted genes, i.e., P53, Caspase-3 and Caspase-9, and the ratio of Bax/Bcl-2, downregulate the transcription of angiogenesis markers, i.e., Vegf and Fgf2 compared with Model group. Furthermore, administration of EPS-09 could increase the abundance of phylum Firmicutes, family Ruminococcaceae and Lachnospiraceae, and genus Ruminococcus, but reduce the abundance of genus Prevotella, Akkermansia and Oscillospira. Taken together, these results indicate that administration of EPS-09 can induce apoptosis of tumor cell, inhibit tumor angiogenesis, improve the immunity, regulate the intestinal microbiota composition of B16F10 melanoma bearing mice, and play positive roles in the antitumor activity against melanoma.

Update of Diagnosis and Targeted Therapy for ALK+ Inflammation Myofibroblastic Tumor.

OPINION STATEMENT: Inflammatory myofibroblastic tumor (IMT), characterized by intermediate malignancy and a propensity for recurrence, has presented a formidable clinical challenge in diagnosis and treatment. Its pathological characteristics may resemble other neoplasms or reactive lesions, and the treatment was limited, taking chemotherapies as the only option for those inoperable. However, discovering anaplastic lymphoma kinase (ALK) protein expression in approximately 50% of IMT cases has shed light on a new diagnostic approach and application of targeted therapies. With the previous success of combating ALK+ non-small-cell lung cancers with ALK tyrosine kinase inhibitors (TKIs), crizotinib, a first-generation ALK-TKI, was officially approved by the U.S. Food and Drug Administration in 2020, to treat unresectable ALK+ IMT. After the approval of crizotinib, other ALK-TKIs, such as ceritinib, alectinib, brigatinib, and lorlatinib, have proven their efficacy on ALK+ IMT with sporadic case reports. The sequential treatments of targeted therapies in may provide the insight into the choice of ALK-TKIs in different lines of treatment for unresectable ALK+ IMT.