TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Case Report: sintilimab-induced Stevens-Johnson Syndrome in a patient with advanced lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) have been widely applicated in clinical therapy in recent years. Skin-related adverse reaction is one of the most common adverse events for ICIs. Stevens-Johnson syndrome (SJS) is one of the serious cutaneous reactions threatening the life. Here, we reported a case of 76-year-old male patient with poorly differentiated metastatic lung adenocarcinoma, after 9 weeks exposure of sintilimab (3 doses) combined with paclitaxel liposome after concurrent chemotherapy/radiotherapy, experienced Stevens-Johnson syndrome involving limbs, trunk, lip and the oral mucosa. Biopsy of the skin tissue showed infiltration of CD4 and CD8 positive T lymphocytes. We also found PD-L1 expression in the glands and the basal layer of the skin. This finding is distinct from the previously reported expression of PD-L1 on the surface of epidermal keratinocytes in patients with SJS due to immunotherapy.

Case report: Two case reports of cryptogenic brain abscess caused by Fusobacterium nucleatum and literature review.

Brain abscess originates from a localized cerebritis area of brain parenchyma, remaining a refractory infectious disease in the central nervous system. Causative pathogens can be wide-ranging, including bacteria, fungi, or parasites; thus, precise pathogen identification and individualized antimicrobial therapy determine patients' outcomes. Here, we report two cases where both patients only presented with limb dysfunction, but without symptoms, signs, or biological evidence of infection. Samples were obtained through brain stereoscopic surgeries and microbial identifications were performed to confirm the infection of Fusobacterium nucleatum. Further appropriate treatments were given, and the patients recovered well. Patient 1 was a 73-year-old male with a 20-day history of left-sided limbs weakness. A brain MRI showed a space-occupying lesion with a heterogeneously ring-enhancement character in the right frontal lobe. This patient underwent puncture biopsy of the lesion with robot-assisted guidance to confirm a brain abscess. Empirical antibiotic therapy was immediately given until the pathogen was identified as Fusobacterium nucleatum; thus, he received specific antibiotic therapy with metronidazole and recovered well after treatment. Patient 2 was a 22-year-old female with heart disease history who complained of right-sided limb weakness for nine days. A brain MRI showed a circular enhanced lesion with a thin capsule wall and surrounding edema in the left frontal lobe. This patient underwent puncture drainage of the lesion with robot-assisted guidance and a brain abscess was confirmed. Empirical antibiotic therapy was given until the pathogen was identified as Fusobacterium nucleatum and then she also received metronidazole treatment. Her symptoms recovered and the lesion disappeared after 1 month. Hence, we reviewed the diagnosis and treatment of cryptogenic brain abscess caused by Fusobacterium nucleatum and highlight that precise neurosurgical interventions and identification of causative pathogens are crucial for the management of brain abscess.

Coexistence of craniopharyngioma and meningioma: Two rare cases and literature review.

Most of the craniopharyngioma is considered to derive from residual epithelial cells during the craniopharyngeal canal degeneration. Meningioma accounting for the primary intracranial neoplasm is considered to be mainly derived from cells of arachnoid granulations. Nevertheless, rare cases show coexistence of craniopharyngioma and meningioma.Case 1: A 43-year-old male patient referred to the hospital due to paroxysmal headache combined with blurred vision for 1 month. On physical examination, the visual acuity of left eye was poorer than that of the right eye. The visual acuity of the right eye near the nasal part showed defect.MRI and pathological examination were performed. The patient received intracranial tumor resection. After surgery, the patient showed hormone disorder, followed by corresponding treatment. However, the patient was lost in the 6-month follow-up.Case 2: The 64-year-old male patient presented to our department due to decline of visual acuity within 1 year combined with polydipsia (5,000 ml per day), polyuria and fatigue for 6 months. On physical examination, the bilateral visual acuity showed decline, especially the temporal part which was nearly hemiscotosis. MRI was performed. The adamantinomatous craniopharyngioma was diagnosed with the HE staining findings. The patient received intracranial resection. After surgery, the patient was in a deep coma condition, and was lost in the follow-up.In this case study, we presented 2 patients with coexistence of craniopharyngioma and meningioma. In addition, a complete literature review was carried out to illustrate the studies on coexistence of craniopharyngioma and meningioma. Meanwhile, we tried to explain the possible mechanisms for such condition.

[Knockdown of CART1 induces S phase arrest and inhibits invasion and migration of MDA-MB-231 breast cancer cells].

OBJECTIVE: To investigate the effect of exogenous small interference RNA(siRNA)-mediated silencing of the cartilage homeoprotein 1 (CART1) gene on cell biological behavior in MDA-MB-231 human breast cancer cells. METHODS: We designed and chemically synthesized siRNA targeting CART1 or control, and then siRNA was transfected into MDA-MB-231 cells using RNAiMAX. The suppression effect of siRNA on CART1 expression was determined by real-time quantitative PCR and Western blotting. The effects of CART1 knockdown on MDA-MB-231 cell invasion, proliferation and cell cycle were detected by TranswellTM invasion assay, CCK-8 assay and flow cytometry, respectively. RESULTS: CART1-siRNA could significantly suppress the expression of CART1 mRNA and protein as compared with the control group. MDA-MB-231 cells transfected with CART1 siRNA had lower capacity of invasion and proliferation compared with the control group. What's more, the cell ratio increased in S phase and decreased in G2/M in the CART1 siRNA-transfected cells. CONCLUSION: Knockdown of the CART1 gene could significantly inhibit cell invasion and proliferation and induce cell cycle arrest in S phase in MDA-MB-231 human breast cancer cells.