Case report: Envafolimab causes local skin necrosis.

Envafolimab is a Chinese domestic innovative fusion of a humanized single-domain programmed death-ligand 1 (PD-L1) antibody (dAb) and human immunoglobulin IgG1 crystalline fragment (Fc) developed for subcutaneous injections. It was granted conditional market authorization by the China National Medical Product Administration (NMPA) in December 2021. Envafolimab is used to treat adult patients with previously treated microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) advanced solid tumors, including patients with advanced colorectal cancer disease progression who were previously administered fluorouracil, oxaliplatin, and irinotecan, as well as other patients with advanced solid tumors who experienced disease progression after receiving standard treatment and had no other alternative treatment options. However, the lack of post-marketing clinical trial data requires conducting more clinical studies on the safety and efficacy of envafolimab in order to provide scientific basis and a reference for future therapeutic applications. In this paper, we report a case of severe skin necrosis and bleeding in the area of injection after subcutaneous administration of envafolimab in a patient diagnosed with hepatocellular carcinoma. We discuss issues that must be considered before administration of a PD-L1 inhibitor subcutaneously, which could induce immune mechanisms leading to skin necrosis in the area of injection.

Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns.

Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.

Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a shortage of effective biomarkers for its diagnosis. AIM: To explore blood exosomal micro ribonucleic acids (miRNAs) as potential biomarkers for HCC diagnosis. RESULTS: The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p. The miRNA profiles also revealed the tumor stages of HCC patients. High expression of miR-455-5p and miR-30c-5p, which significantly correlated with better overall survival in tumor tissues, could also be detected in blood exosomes. Two pairs of miRNAs (miR-584-5p/miR-106-3p and miR-628-3p/miR-941) showed a 94.1% sensitivity and 68.4% specificity to differentiate HCC patients from non-HCC patients. The specificity of the combination was substantially influenced by alcohol consumption habits. CONCLUSION: This study suggested that blood exosomal miRNAs can be used as new non-invasive diagnostic tools for HCC. However, their accuracy could be affected by tumor stage and alcohol consumption habits.

Exosomal microRNAs as potential biomarkers for cancer cell migration and prognosis in hepatocellular carcinoma patient-derived cell models.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and current treatments exhibit limited efficacy against advanced HCC. The majority of cancer-related deaths are caused by metastasis from the primary tumor, which indicates the importance of identifying clinical biomarkers for predicting metastasis and indicating prognosis. Patient-derived cells (PDCs) may be effective models for biomarker identification. In the present study, a wound healing assay was used to obtain 10 fast-migrated and 10 slow-migrated PDC cultures from 36 HCC samples. MicroRNA (miRNA) signatures in PDCs and PDC-derived exosomes were profiled by microRNA-sequencing. Differentially expressed miRNAs between the low- and fast-migrated groups were identified and further validated in 372 HCC profiles from The Cancer Genome Atlas (TCGA). Six exosomal miRNAs were identified to be differentially expressed between the two groups. In the fast-migrated group, five miRNAs (miR-140-3p, miR-30d-5p, miR-29b-3p, miR-130b-3p and miR-330-5p) were downregulated, and one miRNA (miR-296-3p) was upregulated compared with the slow-migrated group. Pathway analysis demonstrated that the target genes of the differentially expressed miRNAs were significantly enriched in the 'focal adhesion' pathway, which is consistent with the roles of these miRNAs in tumor metastasis. Three miRNAs, miR-30d, miR-140 and miR-29b, were significantly associated with patient survival. These findings indicated that these exosomal miRNAs may be candidate biomarkers for predicting HCC cell migration and prognosis and may guide the treatment of advanced HCC.

Antineoplastic activity of Newcastle disease virus strain D90 in oral squamous cell carcinoma.

Newcastle disease virus (NDV), an avian paramyxovirus, possesses the ability to kill tumor cells. Here, we report the effects of NDV strain D90, which was isolated in China, against oral squamous cell carcinoma (OSCC) cells. In this study, we showed that the cell death induced by D90 was apoptotic. Furthermore, the apoptosis induced by D90 was dependent on the mitochondrial pathway, and the death receptor pathway may be not involved. Bax and Bcl-2 also played a role in the apoptosis induced by D90. Lymph node metastasis is a serious problem for oral cancer; we therefore evaluated the impact of D90 on the migration and invasion of OSCC cells. NDV D90 affected microtubules and microfilaments to inhibit the motility of OSCC prior to apoptosis. The effects of D90 on the migration and invasion rates of OSCC cells were evaluated by migration and invasion assays. Subsequently, the changes in sp1, RECK, MMP-2, and MMP-9 induced by a low concentration of D90 were detected by western blot and gelatin zymography. D90 significantly inhibited the invasion and metastasis of OSCC cells by decreasing the expression of sp1 and increasing the expression of RECK to suppress the expression and activity of MMP-2 and MMP-9.

Incidence of port-site metastasis after undergoing robotic surgery for biliary malignancies.

AIM: To investigate the incidence of clinically detected port-site metastasis (PSM) in patients who underwent robotic surgery for biliary malignancies. METHODS: Using a prospective database, the patients undergoing fully robotic surgery for biliary malignancies between January 2009 and January 2011 were included. Records of patients with confirmed malignancy were reviewed for clinicopathological data and information about PSM. RESULTS: Sixty-four patients with biliary tract cancers underwent robotic surgery, and sixty patients met the inclusion criteria. The median age was 67 year (range: 40-85 year). During a median 15-mo follow-up period, two female patients were detected solitary PSM after robotic surgery. The incidence of PSM was 3.3%. Patient 1 underwent robotic anatomatic left hemihepatectomy and extraction of biliary tumor thrombi for an Klatskin tumor. She had a subcutaneous mass located at the right lateral abdominal wall near a trocar scar. Patient 2 underwent robotic pancreaticoduodenectomy for distal biliary cancer. She had two metachronous subcutaneous mass situated at the right lateral abdominal wall under a same trocar scar at 7 and 26 mo. The pathology of the excised PSM masses confirmed metastatic biliary adenocarcinoma. CONCLUSION: The incidence of PSMs after robotic surgery for biliary malignancies is relatively low, and biliary cancer can be an indication of robotic surgery.