ACADL suppresses PD-L1 expression to prevent cancer immune evasion by targeting Hippo/YAP signaling in lung adenocarcinoma.

Lung cancer is the leading cause of cancer-related death. Cancer immune evasion is a key barrier in the treatment of lung cancer and the development of effective anticancer therapeutics. Long-chain Acyl-CoA dehydrogenase (ACADL), a key enzyme that regulates ß-oxidation of long-chain fatty acyl-CoAs, has been found to act as a tumor suppressor in cancers. However, the role of ACADL in lung adenocarcinoma (LUAD) has not been explored. In the current study, we find that ACADL functions as a tumor suppressor in LUAD to inhibit proliferation and enhanced chemotherapeutic drug-induced apoptosis. Interestingly, ACADL prevents tumor immune evasion by suppressing PD-L1 expression in LUAD. ACADL is critical for Hippo/YAP pathway-mediated PD-L1 regulation. Moreover, YAP activation is essential for ACADL suppression of PD-L1 transcription. In addition, ACADL increases the protein stability and kinase activity of LATS kinase to inhibit YAP activation and PD-L1 transcription. Furthermore, we show that ACADL expression is positively correlated with a better OS and FP in LUAD. Our data reveals that ACADL could be a promising target for regulating Hippo/YAP pathway to prevent tumor immune evasion in LUAD.

NDR1 activates CD47 transcription by increasing protein stability and nuclear location of ASCL1 to enhance cancer stem cell properties and evasion of phagocytosis in small cell lung cancer.

Small cell lung cancer (SCLC) is one of the most malignant types of lung cancer. Cancer stem cell (CSC) and tumor immune evasion are critical for the development of SCLC. We previously reported that NDR1 enhances breast CSC properties. NDR1 might also have a role in the regulation of immune responses. In the current study, we explore the function of NDR1 in the control of CSC properties and evasion of phagocytosis in SCLC. We find that NDR1 enhances the enrichment of the ALDEFLUORhigh and CD133high population, and promotes sphere formation in SCLC cells. Additionally, NDR1 upregulates CD47 expression to enhance evasion of phagocytosis in SCLC. Furthermore, the effects of NDR1 enhanced CD47 expression and evasion of phagocytosis are more prominent in CSC than in non-CSC. Importantly, NDR1 promotes ASCL1 expression to enhance NDR1-promoted CSC properties and evasion of phagocytosis in SCLC cells. Mechanically, NDR1 enhances protein stability and the nuclear location of ASCL1 to activate the transcription of CD47 in SCLC. Finally, CD47-blocking antibody can be used to target NDR1 enhanced CSC properties and evasion of phagocytosis by suppressing EGFR activation in SCLC. In summary, our data indicate that NDR1 could be a critical factor for modulating CSC properties and phagocytosis in SCLC.

Intestinal intussusception caused by intestinal duplication and ectopic pancreas: A case report and review of literature.

BACKGROUND: Intestinal intussusception caused by intestinal duplication and ectopic pancreas is extremely rare in the clinic and has not been reported previously. CASE SUMMARY: A 29-year-old man was admitted to the hospital for chronic abdominal pain and bloating. The preoperative diagnosis was intestinal obstruction and intussusception. Then, laparotomy, partial small intestinal resection and extraintestinal decompression were performed. Postoperative pathology confirmed intestinal duplication and ectopic pancreas. After surgery, the patient recovered well with no complications. No recurrence was observed after more than 5 mo of follow-up. CONCLUSION: We report a new case of a young male with intussusception caused by intestinal duplication and ectopic pancreas. Surgery is the main treatment for these conditions. This study aimed to raise awareness and provide information to improve the clinical management of this rare yet serious condition.

Perianal superficial CD34-positive fibroblastic tumor: A case report.

BACKGROUND: Superficial CD34-positive fibroblast tumors (SCPFTs) are newly recognized fibroblast and myofibroblast tumors representing intermediate tumors. To the best of our knowledge, fewer than 50 cases have been reported. Perianal SCPFT has not been previously reported. CASE SUMMARY: A 55-year-old man was hospitalized upon discovering a painless perianal lump 10 d prior. Physical examination showed a lump of approximately 3 cm × 4 cm in the 7 to 8 o'clock direction in the perianal area. Perianal abscess was considered the primary diagnosis. Lump removal surgery was performed under epidural anesthesia. Postoperative pathology showed a well-circumscribed, soft tissue-derived, spindle-cell tumor with strong CD34 positivity by immunohistochemistry. The final diagnosis was perianal SCPFT. There were no complications, and the patient was followed for more than 8 mo without recurrence or metastasis. CONCLUSION: We report a case of perianal superficial CD34-positive fibroblast tumor. This rare mesenchymal neoplasm has distinctive histomorphology, which is important for diagnosis. Comprehensive consideration of clinical information, imaging, histology, and immunohistochemistry is important for diagnosis.

ß-Asarone suppresses Wnt/ß-catenin signaling to reduce viability, inhibit migration/invasion/adhesion and induce mitochondria-related apoptosis in lung cancer cells.

Lung cancer is the leading cause of cancer death worldwide. Chemotherapy is one of the most effective strategies for lung cancer treatment. However, the side effects of chemotherapy limit the application of chemotherapeutic agents. The ß-Asarone, a low-toxicity natural compound from a traditional Chinese medicinal herb, has been demonstrated to display anticancer activities in multiple cancer types. However, the anticancer activities of ß-Asarone in lung cancer have not been shown, and the underlying molecular mechanisms are still unclear. In the current study, we show that ß-Asarone displays a dose-dependent inhibitory effect on the viability of lung cancer cells. Additionally, ß-Asarone significantly suppresses the cell migration, invasion, and adhesion of lung cancer cells. Moreover, ß-Asarone induces apoptosis associated with the activation of caspase-9 and caspase-3, the upregulation of XAF1, Puma, Bax (Ser184) and Bad (Ser112), the downregulation of XIAP, Bcl-2 and Survivin, the translocation of Bax, Bad, phospho-Bax (Ser184), phospho-Bad (Ser112) and cytochrome C and the reduction of the mitochondrial membrane potential. Mechanistically, our study shows that ß-Asarone inhibits Wnt/ß-catenin signaling. Rescuing the activation of Wnt/ß-catenin signaling overcomes ß-Asarone-induced anticancer effects. Taken together, our data provide the first evidence of the anticancer effects of ß-Asarone in lung cancer, demonstrates that the inhibition of Wnt/ß-catenin signaling could be critical for ß-Asarone-induced anticancer effects. Our study thus suggests a potential application of ß-Asarone as an anticancer agent in the clinical treatment of lung cancer.

[Short-term efficacy of cetuximab combined with radiotherapy or chemotherapy on head and neck cancer: a report of 11 cases].

BACKGROUND AND OBJECTIVE: Cetuximab combined with radiotherapy or chemotherapy has been used to treat head and neck cancer in recent years, but few reports are available in China now. This study was to summarize our experiences in treating patients with head and neck cancer cetuximab. METHODS: From October 1st, 2005 to September 30th, 2008, six with patients head and neck cancer were treated using cetuximab combined with radiotherapy and five were treated using cetuximab combined with chemotherapy in Sun Yat-sen University Cancer Center. The short-term efficacy and safety were analyzed. RESULTS: A total of 82 cycles of cetuximab treatment, with a median of seven cycles, were administered safely. There was no treatment-associated death and no cetuximab-associated discontinuation. In cetuximab combined with radiotherapy group, four patients achieved complete response (CR) and two achieved partial response (PR); all CR patients had hadacne-like rash (three cases were > or = grade III), only one PR patient had grade I rash; five patients had skin reaction in the irradiation field (four cases of skin reaction were > or = grade III); hematological toxicity was slight excepted one case of grade IV. In cetuximab combined chemotherapy group, two patients achieved PR, two had stable disease (SD) and one had progressed disease (PD); the of acne-like rash was low, and three patients experienced bone marrow depression above grade III. CONCLUSION: Cetuximab combined with either radiotherapy or chemotherapy are good options for suitable patients with head and neck cancer.