Chang Liu

Reshaping Intratumoral Mononuclear Phagocytes with Antibody‐Opsonized Immunometabolic Nanoparticles

AbstractMononuclear phagocytes (MPs) are vital components of host immune defenses against cancer. However, tumor‐infiltrating MPs often present tolerogenic and pro‐tumorigenic phenotypes via metabolic switching triggered by excessive lipid accumulation in solid tumors. Inspired by viral infection‐mediated MP modulation, here enveloped immunometabolic nanoparticles (immeNPs) are designed to co‐deliver a viral RNA analog and a fatty acid oxidation regulator for synergistic reshaping of intratumoral MPs. These immeNPs are camouflaged with cancer cell membranes for tumor homing and opsonized with anti‐CD163 antibodies for specific MP recognition and uptake. It is found that internalized immeNPs coordinate lipid metabolic reprogramming with innate immune stimulation, inducing M2‐to‐M1 macrophage repolarization and tolerogenic‐to‐immunogenic dendritic cell differentiation for cytotoxic T cell infiltration. The authors further demonstrate that the use of immeNPs confers susceptibility to anti‐PD‐1 therapy in immune checkpoint blockade‐resistant breast and ovarian tumors, and thereby provide a promising strategy to expand the potential of conventional immunotherapy.

Data‐independent acquisition for proteomic applications in early‐stage endometrial cancer progression

AbstractAimMost endometrial cancer (EC) patients are diagnosed at an early‐stage (FIGO stage I or II), with a favorable prognosis. However, some high‐grade, early‐stage EC patients have unexpected recurrences and undesirable results, the molecular alterations that underlie these tumors are far from being fully understood. Our goal was to use proteome analysis to examine dysregulated pathways in this specific subgroup of EC.MethodsWe used data‐independent acquisition (DIA) quantitative proteomics to analyze cancer and matched paracancerous tissues from 20 EC patients (10 high‐grade and 10 low‐grade). Immunohistochemistry (IHC) analysis was used to validate protein expression of six hub genes.ResultsIn total, 7107 proteins were quantified, while 225 downregulated and 366 upregulated proteins in high‐grade cancer tissues, 130 downregulated and 413 upregulated proteins in high‐grade paracancerous tissues. The pathway associated with oxidative phosphorylation (OXPHOS) was upregulated and have similar expression patterns in high‐grade EC tissues and matched paracancerous tissues. OXPHOS‐related protein, ATP5F1D showed the best classification and diagnostic ability in distinguishing high‐grade from low‐grade EC. In both cancer and paracancerous tissues, double‐label immunofluorescence demonstrated ITGA4 and COL4A1 co‐localized at the basal membrane.ConclusionsOur present works elucidate that metabolism reprogramming is associated with high‐grade, early‐stage EC, particularly OXPHOS is upregulated. Noticeably, the paracancerous tissues have undergone molecular changes similar to cancer tissues, maybe they have signal exchange via secreted proteins (ITGA4 and COL4A1). The upregulation of OXPHOS‐related proteins may be the potential biomarker for EC diagnosis, and targeting OXPHOS metabolism might be an effective treatment for high‐grade, early‐stage EC.

Inhibition of squalene epoxidase linking with PI3K/AKT signaling pathway suppresses endometrial cancer

AbstractEndometrial cancer (EC) is a common malignant tumor that lacks any therapeutic target and, in many cases, recurrence is the leading ca use of morbidity and mortality in women. Widely known EC has a strongly positive correlation with abnormal lipid metabolism. Squalene epoxidase (SQLE), a crucial enzyme in the cholesterol synthesis pathway regulating lipid metabolic processes has been found to be associated with various cancers in recent years. Here, we focused on studying the role of SQLE in EC. Our study revealed that SQLE expression level was upregulated significantly in EC tissues. In vitro experiments showed that SQLE overexpression significantly promoted the proliferation, and inhibited cell apoptosis of EC cells, whereas SQLE knockdown or use of terbinafine showed the opposite results. Furthermore, we found out that the promotional effect of SQLE on the proliferation of EC cells might be achieved by activating the PI3K/AKT pathway. In vivo, studies confirmed that the knockdown of SQLE or terbinafine can observably inhibit tumor growth in nude mice. These results indicate that SQLE may promote the progression of EC by activating the PI3K/AKT pathway. Moreover, SQLE is a potential target for EC treatment and its inhibitor, terbinafine, has the potential to become a targeted drug for EC treatment.

Malignant transformation of hepatic endometriosis: a case report and literature review

Abstract Background Extrapelvic endometriosis is defined as the presence of ectopic endometrial tissue in structures outside the pelvis. Although extra-pelvic endometriosis is generally considered benign conditions, malignant potential within endometriotic foci occurs even after definitive surgery. Malignant transformation of hepatic endometriosis is extremely rare. Preoperative diagnosis of this cancer is difficult, and no guidelines on the optimal management currently exist. Here, we present a case report of malignant transformation of hepatic endometriosis and a brief literature review to highlight the current knowledge of the prevalence, clinical features, diagnosis, and management of this condition. Case presentation A 50-year-old woman with a 2-year duration of progressive right upper quadrant abdominal pain was admitted to the hospital. She underwent hysterectomy and bilateral salpingo-oophorectomy for benign conditions 4 years prior. Tumor markers demonstrated elevated carbohydrate antigen (CA)-199 112U/mL (normal range: 0–35U/mL) only. Radiological imaging suggested the presence of a 10.7 × 7.7-cm mass in the right lobe of the liver extending to the diaphragm. The intraoperative frozen sections suggested malignant tumor. Right hepatectomy with infiltrating diaphragm resection was performed. The final pathology with immunohistochemistry staining confirmed endometrioid adenocarcinoma in the liver originating from preexisting hepatic endometriosis. After the multidisciplinary team meeting, the consensus was surgery followed by adjuvant chemotherapy. To our knowledge, this is the first case of Chinese woman of a malignant liver tumor originating from endometriosis ever reported by reviewing the current English medical literature. Conclusion Though rare, extrapelvic endometriosis-associated cancers should be considered as differentiated diagnosis even after hysterectomy and bilateral salpingo-oophorectomy. This case highlights the importance of collaborative efforts across multiple disciplines for accurate diagnosis and appropriate treatment of malignant transformation of hepatic endometriosis.