Pancreatic Adenocarcinoma (PDAC) is one of the most deadly malignant tumors worldwide. A variety of mechanisms are involved in PDAC biological behaviors, of which, the mechanisms of immune escape may be a pivotal hallmark. HLA-G is a tolerant molecule implicated in tumor escape and serves as a prognostic biomarker in tumors. Our study evaluated the expression of HLA-G in PDAC and explored its clinical significance. In a cohort of 122 PDAC patients, 78 patents (63.9%) exhibited high level of HLA-G tumor tissues. Multivariate analysis suggested that HLA-G level was an independent predictor for OS (HR = 3.894, 95% CI = 2.380-6.370, p <0.001). High level of HLA-G significantly correlated with PDAC aggressive features, such as more advanced stage (TNM Stage II) (p<0.001), extrapancreatic infiltration (T3 stage) (p<0.001), lymph node involvement (p=0.019) and poor differentiation (p=0.010). In western blot analysis, almost all of the tumor cell lines (5/6) expressed high levels of HLA-G. In ELISA analysis, the level of plasma sHLA-G in PDAC patients were significantly increased than in healthy control (P=0.0037). Further analysis revealed the level of sHLA-G inversely related to numbers of peripheral activated T cells (CD8+CD28+ T cells), which may indicate that sHLA-G inactivates T cell responses resulting in tumor immune escape. In conclusion, tumor-derived HLA-G may indicate the mechanism of immune escape and impaired PDAC clinical outcome, especially in early-stage patients, which may also be a potential therapeutic target.
Pancreatic cancer has an extremely poor prognosis mainly due to lack of effective treatment options. Radiotherapy is mostly applied to locally advanced cases, although tumor radioresistance limits the effectiveness. Profilin1, a novel tumor suppressor gene, was reported to be down-regulated in various cancers and associated with tumor progression. The objective of this study was to demonstrate how profilin1 affected pancreatic cancer radiosensitivity. We showed profilin1 was down-regulated in pancreatic cancer cells after exposure to radiation, and re-expression of profilin1 suppressed tumor cell viability and increased DNA damage following irradiation. Further studies revealed that up-regulation of profilin1 facilitated apoptosis and repressed autophagy induced by irradiation, which might sensitize pancreatic cancer cells to radiation treatment. Our findings may provide a novel therapeutic strategy for sensitizing pancreatic cancer to radiotherapy. Keywords: Apoptosis, autophagy, DNA damage, pancreatic cancer, profilin1, radiation.
Background Poorly differentiated gastric neuroendocrine neoplasms (PDGNENs) include gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma, which are highly malignant and rare tumors, and their incidence has increased over the past few decades. However, the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated. Aim To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs. Methods The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively. Results Among the 232 patients with PDGNENs, 191 (82.3%) were male, with an average age of 62.83 ± 9.11 years. One hundred and thirteen (49.34%) of 229 patients had a stage III disease and 86 (37.55%) had stage IV disease. Three (1.58%) of 190 patients had no clinical symptoms, while 187 (98.42%) patients presented clinical symptoms. The tumors were mainly (89.17%) solitary and located in the upper third of the stomach (cardia and fundus of stomach: 115/215, 53.49%). Most lesions were ulcers (157/232, 67.67%), with an average diameter of 4.66 ± 2.77 cm. In terms of tumor invasion, the majority of tumors invaded the serosa (116/198, 58.58%). The median survival time of the 232 patients was 13.50 mo (7, 31 mo), and the overall 1-year, 3-year, and 5-year survival rates were 49%, 19%, and 5%, respectively. According to univariate analysis, tumor number, tumor diameter, gastric invasion status, American Joint Committee on Cancer (AJCC) stage, and distant metastasis status were prognostic factors for patients with PDGNENs. Multivariate analysis showed that tumor number, tumor diameter, AJCC stage, and distant metastasis status were independent prognostic factors for patients with PDGNENs. Conclusion The overall prognosis of patients with PDGNENs is poor. The outcomes of patients with a tumor diameter > 5 cm, multiple tumors, and stage IV tumors are worse than those of other patients.
Background Insomnia has become increasingly prevalent in modern society and is notoriously difficult to treat. Many patients exhibit a poor response to pharmacological interventions. Stellate ganglion block (SGB) has emerged as an effective method for managing insomnia; however, its efficacy may be compromised in some patients, primarily due to a variant vertebral artery anatomy. Case presentation This case report describes a patient with severe insomnia accompanied by anxiety. Through cervical ultrasound scanning, we identified richly branched cervical arteries at the C6−C7 segment of the vertebral artery, along with anatomical variations, which could pose a heightened risk for the traditional SGB procedure. Therefore, after carefully adjusting the patient’s positioning, we proceeded with ultrasound-guided SGB using a lateral paravein out-of-plane approach. Clinical signs of successful insomnia symptoms alleviation were consistently observed after each block utilizing this alternative technique multiple times in a single patient. Conclusion Our report reveals a new lateral paravein out-of-plane approach for ultrasound-guided SGB to treat insomnia, which might be considered an alternative method. More studies should be carried out to confirm the efficacy of this new approach.
Pancreatic cancer remains a lethal disease and is associated with poor prognosis, particularly for patients with distant metastasis at diagnosis. Recently, Oweira reported a retrospective study that included 13233 metastatic pancreatic cancer patients from the Surveillance, Epidemiology and End Results database. They demonstrated that pancreatic cancer patients with isolated liver metastases had worse outcomes than patients with isolated lung metastases or distant nodal metastases. At present, the standard treatment for metastatic pancreatic cancer is chemotherapy. However, improvement in the safety of pancreatic surgery has led to the consideration of more aggressive surgical approaches. Schneitler reported two cases of hepatic metastatic pancreatic cancer in which negative margin (R0) resection and long survival were achieved after effective preoperative chemotherapy. In general, these two studies indicate that although pancreatic cancer patients with liver metastasis have a poor prognosis, surgical approaches may prolong survival for a few of these patients. A strategy to select hepatic metastatic pancreatic cancer patients who may benefit from surgical intervention is urgently needed.
Tumor-associated tertiary lymphoid structures (TLSs) are functional immune-responsive niches that are not fully understood in pancreatic ductal adenocarcinoma (PDAC).Fluorescent multiplex immunohistochemistry was performed on sequential sections of surgically resected tumor tissues from 380 PDAC patients without preoperative treatment (surgery alone (SA)) and 136 patients pretreated with neoadjuvant treatment (NAT). Multispectral images were processed via machine learning and image processing platforms, inForm V.2.4 and HALO V.3.2; TLS regions were segmented, and the cells were identified and quantified. The cellular composition and immunological properties of TLSs and their adjacent tissues in PDAC were scored and compared, and their association with prognosis was further examined.Intratumoral TLSs were identified in 21.1% (80/380) of patients in the SA group and 15.4% (21/136) of patients in the NAT group. In the SA group, the presence of intratumoral TLSs was significantly associated with improved overall survival (OS) and progression-free survival. The existence of intratumoral TLSs was correlated with elevated levels of infiltrating CD8+T, CD4+T, B cells and activated immune cells in adjacent tissues. A nomogram model was generated with TLS presence as a variable, which successfully predicted PDAC patient OS in an external validation cohort (n=123). In the NAT group, samples exhibited a lower proportion of B cells and a higher proportion of regulatory T cells within intratumoral TLSs. Additionally, these TLSs were smaller in size, with a lower overall maturation level and reduced immune cell activation, and the prognostic value of TLS presence was insignificant in the NAT cohort.Our study systematically revealed the cellular properties and prognostic values of intratumoral TLSs in PDAC and described the potential impact of NAT on TLS development and function.
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