Proteomic profiling and functional characterization of serum-derived extracellular vesicles in the mucinous and non-mucinous colon adenocarcinoma.

PURPOSE: Mucinous adenocarcinoma (MC) is a distinct pathological subtype of colon adenocarcinoma, which is associated with a worse prognosis compared with non-mucinous adenocarcinoma (AC). However, clear distinctions between MC and AC remain unknown. Extracellular vesicles (EVs) are a class of enclosed vesicles containing proteins, lipids, and nucleic acids that are secreted by cells into surrounding tissues or into serum. The EVs could facilitate tumorigenesis by regulating tumor cell proliferation, invasiveness, metastasis, angiogenesis, and evasion of immune surveillance. METHODS: Quantitative proteomics analysis was performed to determine the characterization and biological differences of serum-derived EVs in two subtypes of colon adenocarcinoma (MC and AC). Serum-derived EVs from patients with MC, AC, and healthy volunteers were included in this study. The role of PLA2G2A in cell migration and invasion were evaluate with transwell assay, and its prognostic predictive value was further assessed based on TCGA database. RESULTS: Quantitative proteomics analysis revealed 846 differentially expressed proteins (DEPs) in EVs from MC patients compared with those from AC patients. Bioinformatics analysis revealed that the most prominent protein cluster included those involved in cell migration and the tumor microenvironment. Overexpression of PLA2G2A, one of the key EV proteins upregulated in patients with MC, in colon cancer cell line SW480 promoted the cell invasion and migration ability. In addition, the high level of PLA2G2A is associated with poor prognosis of colon cancer patients harboring BRAF mutations. Further, after EV stimulation, proteomic analysis of recipient SW480 cells showed that MC-derived EVs activated multiple cancer-related pathways, including the Wnt/ß-Catenin signaling pathway, and might promote the malignancy of mucinous adenocarcinoma through these pathways. CONCLUSIONS: The identification of differential protein profiles between MC and AC helps to elucidate the underlying molecular mechanisms of MC pathogenesis. The PLA2G2A in EVs is a potential prognostic predictive marker for those patients harboring with BRAF mutations.

Laparoscopic resection of presacral benign tumors with rectum preservation.

Multiple surgical approaches are available for the treatment of presacral tumors. In patients with presacral tumors, surgical resection is currently the only curative treatment option. However, the anatomical structures of the pelvis are not readily accessible using traditional approaches. Herein, we present a surgical technique for laparoscopic presacral benign tumor resection with rectal preservation. Surgical videos of two patients were used to introduce the laparoscopic procedure. First, the tumor of a 30-year-old woman with presacral cysts was observed during physical examination. As the tumor continued to enlarge, it increased rectal compression and altered bowel habits. The patient's surgical video was used to present complete laparoscopic presacral resection. Several video clips of a second 30-year-old woman with cysts were used to present the details and precautions of the resection. Neither of the patients required conversion to an open surgical approach. Complete surgical excision of the tumors was achieved, without rectal injury. Both patients had no postoperative complications and were discharged on postoperative 5-6 days. The laparoscopic approach for presacral benign tumors is superior in terms of manipulability compared with the conventional approach. Therefore, we recommend that the laparoscopy approach should be considered as the standard surgical approach for presacral benign tumors.

Laparoscopic Resection of Pelvic Schwannomas: A 9-Year Experience at a Single Center.

Background: Pelvic schwannoma (PS), a type of slow-growing and noninvasive neoplasm that occurs in the pelvis, is relatively rare in adults. However, due to the anatomical structures, surgical excision of the tumors is often difficult using the traditional approach. Methods: Data of patients who underwent laparoscopic excision of PS at our hospital between September 2012 and September 2021 were reviewed. All surgeries were performed in the general surgery department. Clinical data were collected from the inpatient and outpatient medical records. Results: In total, 12 patients (median age, 52 years) underwent laparoscopy for PS without conversion to laparotomy. Eight cases of tumors were located in the presacral space, and the others were found in the lateral wall of the pelvis (N = 4). The median operative time was 145 (range, 70-215) minutes, with a median blood loss of 35 (range, 5-200) mL. Among all cases, 3 patients experienced minor postoperative complications. The median postoperative hospital stay was 4 (range, 2-7) days. Moreover, postoperative pathological examinations showed that all PSs were benign. No patient experienced local recurrence during a median follow-up period of 32 (range, 2-106) months. Conclusions: Our findings indicate that laparoscopic resection of PS is feasible, which has a significant advantage in enhancing the accessibility of pelvic structures and preserving nerve and vascular integrities.

The potential role of the three-dimensional-bioprinting model in screening and developing drugs.

Recently, we have read with great interest the original article used different spatial configuration models of colorectal cancer (CRC) for validating the anti-tumor efficacy with Diiminoquinone. We feel obliged to provide new insight into the drug screening models by integrating and analyzing the original method and result. These comments may provide comprehensive insights into three-dimensional drug screening models and the difference between pathologic subtypes in CRC.

Magnetic resonance imaging-based artificial intelligence model in rectal cancer.

Rectal magnetic resonance imaging (MRI) is the preferred method for the diagnosis of rectal cancer as recommended by the guidelines. Rectal MRI can accurately evaluate the tumor location, tumor stage, invasion depth, extramural vascular invasion, and circumferential resection margin. We summarize the progress of research on the use of artificial intelligence (AI) in rectal cancer in recent years. AI, represented by machine learning, is being increasingly used in the medical field. The application of AI models based on high-resolution MRI in rectal cancer has been increasingly reported. In addition to staging the diagnosis and localizing radiotherapy, an increasing number of studies have reported that AI models based on high-resolution MRI can be used to predict the response to chemotherapy and prognosis of patients.

Intra-platelet serotonin and YAP contributed to poor prognosis of hepatocellular carcinoma.

AIMS: Intra-platelet 5-HT (IP 5-HT) and YAP exhibit an important role in hepatocellular carcinoma (HCC). The aim of the study was to investigate whether IP 5-HT and YAP could affect the progression and prognosis of HCC. METHODS: 5-HT level and YAP expression were measured and were compared between HCC patients and control patients. By grouping HCC patients, we analyzed clinical indicators and survival. The predictive nomogram was established by R software according to the risk factors obtained from multivariate analysis. RESULTS: Higher IP 5-HT level and higher YAP expression were associated with poorer prognosis. In addition, they were also associated with BCLC stages. Higher IP 5-HT was found to be related with higher international normalized ratio (INR) (p = 0.040), more death (p = 0.015) and higher YAP expression (p < 0.001). Similarly, higher YAP expression was proved to be associated with lower platelet counts (PLT) (p = 0.032), smaller tumor size (p = 0.017), more death (p < 0.001) and higher IP 5-HT (p < 0.001). In addition, alkaline phosphatase (ALP), YAP and tumor size were proved to be independent risk factors. By using risk factors, we have established a prognostic prediction nomogram for HCC patients. In the prognostic prediction nomogram, patients with higher scores would have poorer prognosis. CONCLUSIONS: IP 5-HT and YAP might affect the progression and prognosis of HCC through synergistic effect. Moreover, IP 5-HT might affect HCC by regulating YAP expression. Thus, both of them might be potential therapeutic targets. By establishing the prognostic prediction nomogram, we could improve the prediction system.

Inhibition of PFKFB3 induces cell death and synergistically enhances chemosensitivity in endometrial cancer.

The advanced or recurrent endometrial cancer (EC) has a poor prognosis because of chemoresistance. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a glycolytic enzyme, is overexpressed in a variety of human cancers and plays important roles in promoting tumor cell growth. Here, we showed that high expression of PFKFB3 in EC cell lines is associated with chemoresistance. Pharmacological inhibition of PFKFB3 with PFK158 and or genetic downregulation of PFKFB3 dramatically suppressed cell proliferation and enhanced the sensitivity of EC cells to carboplatin (CBPt) and cisplatin (Cis). Moreover, PFKFB3 inhibition resulted in reduced glucose uptake, ATP production, and lactate release. Notably, we found that PFK158 with CBPt or Cis exerted strong synergistic antitumor activity in chemoresistant EC cell lines, HEC-1B and ARK-2 cells. We also found that the combination of PFK158 and CBPt/Cis induced apoptosis- and autophagy-mediated cell death through inhibition of the Akt/mTOR signaling pathway. Mechanistically, we found that PFK158 downregulated the CBPt/Cis-induced upregulation of RAD51 expression and enhanced CBPt/Cis-induced DNA damage as demonstrated by an increase in γ-H2AX levels in HEC-1B and ARK-2 cells, potentially revealing a means to enhance PFK158-induced chemosensitivity. More importantly, PFK158 treatment, either as monotherapy or in combination with CBPt, led to a marked reduction in tumor growth in two chemoresistant EC mouse xenograft models. These data suggest that PFKFB3 inhibition alone or in combination with standard chemotherapy may be used as a novel therapeutic strategy for improved therapeutic efficacy and outcomes of advanced and recurrent EC patients.

Axis of serotonin -pERK-YAP in liver regeneration.

BACKGROUND AND AIM: Serotonin and YAP exhibit a vital role in regulating cell proliferation and wound-healing response. The aim of the study was to investigate whether 5-HT could promote liver regeneration by activating YAP. METHODS: PH models were established by WT and TPH1-/- mice. ELISA, RT-PCR, western blot, immunohistochemistry, flow cytometry and MTT assay were used to assess the level of 5-HT and YAP and proliferation after PH. RESULTS: We found that 5-HT level was lower in the serum and liver of TPH1-/- mice. After PH, TPH1-/- mice, lacking in 5-HT, demonstrated worse regenerative ability and suffered more severe liver injury. Additionally, YAP expression was also lower in TPH1-/- mice. Moreover, we found that YAP expression was prominent within the first three days following PH. Similarly, 5-HT could promote cell proliferation by upregulating YAP expression in L-O2 cells. As predicted, using YAP-siRNA sharply reduced the proliferative capacity mediated by 5-HT. Further study also indicated that ERK participated in the regulation of YAP induced by 5-HT. By using an ERK inhibitor, the YAP expression and cell proliferation induced by 5-HT were both suppressed. Although YAP-siRNA was used to block YAP expression, pERK and ERK expression were not affected. Taken together, these data showed that 5-HT contributed to liver regeneration by regulating YAP expression, which at least in part, was by activation of pERK. CONCLUSION: A role of the 5-HT-pERK-YAP axis in liver regeneration emerged from our study and might be a potential target to promote regeneration and injury repair.

Serotonin and YAP/VGLL4 Balance Correlated with Progression and Poor Prognosis of Hepatocellular Carcinoma.

YAP-TEAD complex plays an important role in tumorigenesis. 5-HT is proved to upregulate YAP expression by our previous study and VGLL4 is found to compete with YAP for binding to TEAD in several of cancers. Here, we investigated whether 5-HT could affect progression and prognosis of hepatocellular carcinoma (HCC) patients and regulate YAP/VGLL4 balance. We found that 5-HT and YAP/VGLL4 ratio were higher in HCC patients and closely related with progression and poor prognosis. Furthermore, 5-HT level, YAP/VGLL4 ratio and tumor size were proved as independent risk factors of HCC patients in our study. Based on the independent risk factors, nomogram was established to exactly predict prognosis of HCC patients. Additionally, the study revealed that a higher total point of the nomogram was closely correlated with poorer prognosis. As a result, 5-HT might contribute to the progression and poor prognosis of hepatocellular carcinoma via regulating YAP/VGLL4 balance. Therefore, the established nomogram based on the independent risk factors may become an important part of HCC prediction system and YAP/VGLL4 balance may be a potential therapeutic target in future.