Second primary malignancy post immunotherapy: A case report of 2 cases.

RATIONALE: Immune checkpoint inhibitors have shown high efficacies as the first-line treatment of various advanced malignancies. Yet, the effect and practice patterns of immune checkpoint inhibitors on the second primary tumors are still unclear. Second primary malignancy post immunotherapy, there is paucity in such cases being reported. PATIENT CONCERNS: We report 2 cases of a 57-year-old woman with nonsmall cell lung cancer and a 69-year-old man with metastatic clear cell renal carcinoma treated with immunotherapy who developed second primary malignancies during the therapy. DIAGNOSIS: Second primary malignancy during the therapy. INTERVENTIONS: In addition to the treatments of the second primary malignancies, maintenance immunotherapy was continued for the patients. OUTCOMES: Overall survival in both patients was longer than 12 months, and the treatments were well tolerated. The adverse reactions mainly included depigmentation of hair and facial and limb skin in patient 1 and diarrhea in patient 2. LESSONS: It is necessary to recognize that the second primary malignancy may occur during the immunotherapy, and more clinical studies and practices are still needed for the adjustment of the regimens of immunotherapy. Full diagnosis, timely treatment, and long-term regular follow-up have important significance for patients with malignancies.

(-)-Guaiol triggers immunogenic cell death and inhibits tumor growth in non-small cell lung cancer.

(-)-Guaiol is a sesquiterpenoid found in many traditional Chinese medicines with potent antitumor activity. However, its therapeutic effect and mechanism in non-small cell lung cancer (NSCLC) have not been fully elucidated. In this study, (-)-Guaiol was found to induce immunogenic cell death (ICD) in NSCLC in vitro. Using (-)-Guaiol in vivo, we found that (-)-Guaiol could suppress tumor growth, increase dendritic cell activation, and enhance T-cell infiltration. Vaccination experiments suggest that cellular immunoprophylaxis after (-)-Guaiol intervention can suppress tumor growth. Previous studies have found that (-)-Guaiol induces apoptosis and autophagy in NSCLC. Apoptosis and autophagy are closely related to ICD. To explore whether autophagy and apoptosis are involved in (-)-Guaiol-induced ICD, we used inhibitors of apoptosis and autophagy. The results showed that the release of damage-associated molecular patterns (DAMPs) was partly reversed after inhibition of apoptosis and autophagy. In conclusion, these results suggested that the (-)-Guaiol triggers immunogenic cell death and inhibits tumor growth in NSCLC.

Curcumin suppresses renal carcinoma tumorigenesis by regulating circ-FNDC3B/miR-138-5p/IGF2 axis.

Curcumin has a vital role in the development of renal carcinoma. Nevertheless, the mechanism of curcumin in renal carcinoma tumorigenesis remains largely unknown. Thirty renal carcinoma patients were recruited. Renal carcinoma cell lines CAKI-1 and ACHN were exposed to curcumin. The levels of circular RNA fibronectin type III domain-containing protein 3B (circ-FNDC3B), microRNA (miR)-138-5p and insulin-like growth factor 2 (IGF2) were detected via quantitative reverse transcription PCR or western blot. Cell proliferation and apoptosis were investigated via 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide, colony formation analysis, flow cytometry and western blot. Target association between miR-138-5p and circ-FNDC3B or IGF2 was analyzed via dual-luciferase reporter analysis. The function of curcumin in vivo was assessed via a xenograft model. circ-FNDC3B level was enhanced and miR-138-5p abundance was declined in renal carcinoma tissues and cells. Curcumin restrained renal carcinoma cell proliferation and promoted apoptosis. circ-FNDC3B overexpression or miR-138-5p knockdown weakened the influence of curcumin. circ-FNDC3B knockdown hindered cell proliferation and promoted apoptosis by increasing miR-138-5p. IGF2 was targeted via miR-138-5p and positively regulated via circ-FNDC3B. Curcumin decreased xenograft tumor growth via reducing circ-FNDC3B in vivo. Curcumin suppressed renal carcinoma tumorigenesis in vitro and in vivo via regulating circ-FNDC3B/miR-138-5p/IGF2 axis, proposing new insight into renal carcinoma tumorigenesis.