Advances in basic research, clinical diagnosis and treatment of pancreatic cancer in 2023

Pancreatic cancer is a highly malignant digestive tract tumor with hidden symptoms, limited treatment options and rapid progression. With an increasing incidence rate year by year, pancreatic cancer has increasingly become a prominent issue endangering public health, causing a huge social burden. Although there was no significant improvement in survival rates for pancreatic cancer patients in the past two decades, recent progress in epidemiology, basic research and clinical research of pancreatic cancer has accelerated significantly compared to the past. Some findings have already enabled a small proportion of pancreatic cancer patients to achieve better survival. This article provided a review of the significant progress made in research, diagnosis and treatment of pancreatic cancer in 2023

Novel strategy for oncogenic alteration-induced lipid metabolism reprogramming in pancreatic cancer

The pathogenesis of pancreatic cancer involves substantial metabolic reprogramming, resulting in abnormal proliferation of tumor cells. This tumorigenic reprogramming is often driven by genetic mutations, such as activating mutations of the KRAS oncogene and inactivating or deletions of the tumor suppressor genes SMAD4, CDKN2A, and TP53, which play a critical role in the initiation and development of pancreatic cancer. As a normal cell gradually develops into a cancer cell, a series of signature characteristics are acquired: activation of signaling pathways that sustain proliferation; an ability to resist growth inhibitory signals and evade apoptosis; and an ability to generate new blood vessels and invade and metastasize. In addition to these features, recent research has revealed that metabolic reprogramming and immune escape are two other novel characteristics of tumor cells. The effect of the interactions between tumor and immune cells on metabolic reprogramming is a key factor determining the antitumor immunotherapy response. Lipid metabolism reprogramming, a feature of many malignancies, not only plays a role in maintaining tumor cell proliferation but also alters the tumor microenvironment by inducing the release of metabolites that in turn affect the metabolism of normal immune cells, ultimately leading to the attenuation of the antitumor immune response and resistance to immunotherapy. Pancreatic cancer has been found to have substantial lipid metabolism reprogramming, but the mechanisms remain elusive. Therefore, this review focuses on the mechanisms regulating lipid metabolism reprogramming in pancreatic cancer cells to provide new therapeutic targets and aid the development of new therapeutic strategies for pancreatic cancer

Innate Lymphoid Cells: Emerging Players in Pancreatic Disease

Common pancreatic diseases have caused significant economic and social burdens worldwide. The interstitial microenvironment is involved in and plays a crucial part in the occurrence and progression of pancreatic diseases. Innate lymphoid cells (ILCs), an innate population of immune cells which have only gradually entered our visual field in the last 10 years, play an important role in maintaining tissue homeostasis, regulating metabolism, and participating in regeneration and repair. Recent evidence indicates that ILCs in the pancreas, as well as in other tissues, are also key players in pancreatic disease and health. Herein, we examined the possible functions of different ILC subsets in common pancreatic diseases, including diabetes mellitus, pancreatitis and pancreatic cancer, and discussed the potential practical implications of the relevant findings for future further treatment of these pancreatic diseases

Image_1_Neoadjuvant therapy alters the immune microenvironment in pancreatic cancer.jpeg

Pancreatic cancer has an exclusive inhibitory tumor microenvironment characterized by a dense mechanical barrier, profound infiltration of immunosuppressive cells, and a lack of penetration of effector T cells, which constitute an important cause for recurrence and metastasis, resistance to chemotherapy, and insensitivity to immunotherapy. Neoadjuvant therapy has been widely used in clinical practice due to its many benefits, including the ability to improve the R0 resection rate, eliminate tumor cell micrometastases, and identify highly malignant tumors that may not benefit from surgery. In this review, we summarize multiple aspects of the effect of neoadjuvant therapy on the immune microenvironment of pancreatic cancer, discuss possible mechanisms by which these changes occur, and generalize the theoretical basis of neoadjuvant chemoradiotherapy combined with immunotherapy, providing support for the development of more effective combination therapeutic strategies to induce potent immune responses to tumors.</p

Improving Breakdown Voltage for a Novel SOI LDMOS with a Lateral Variable Doping Profile on the Top Interface of the Buried Oxide Layer

In order to achieve a high breakdown voltage (BV) for the SOI (Silicon-On-Insulator) power device in high voltage ICs, a novel high voltage n-channel lateral double-diffused MOS (LDMOS) with a lateral variable interface doping profile (LVID) placed at the interface between the SOI layer and the buried-oxide (BOX) layer (LVID SOI) is researched. Its breakdown mechanism is investigated theoretically, and its structure parameters are optimized and analyzed by 2D simulation software MEDICI. In the high voltage blocking state, the high concentration ionized donors in the depleted LVID make the surface electric field of SOI layer (ES) more uniform and enhance the electric field of BOX layer (EI), which can prevent the lateral premature breakdown and result in a higher BV. Compared with the conventional uniformly doped (UD) SOI LDMOS, EI of the optimized LVID SOI LDMOS is enhanced by 79% from 119 V/μm to 213 V/μm, and BV is increased by 33.4% from 169 V to 227 V. Simulations indicate that the method of LVID profile can significantly improve breakdown voltage for the SOI LDMOS

TGF-β1-induced RAP2 regulates invasion in pancreatic cancer

Pancreatic cancer is highly lethal due to its aggressive invasive properties and capacity for metastatic dissemination. Additional therapeutic targets and effective treatment options for patients with tumours of high invasive capacity are required. Ras-related protein-2a (RAP2) is a member of the GTP-binding proteins. RAP2 has been reported to be widely upregulated in many types of cancers via regulating cytoskeleton reorganization, cell proliferation, migration, and adhesion, as well as inflammation. As a member of the RAS oncogene family, which has been demonstrated to drive pancreatic cancer oncogenesis and many other malignancies, the physiological roles of RAP2 in pancreatic cancer have seldom been discussed. In the present study, we explored the correlation between RAP2 expression and the prediction of overall survival of pancreatic cancer patients. Mechanistic studies were carried out to shed light on the role of RAP2 in pancreatic cancer invasion and how RAP2 is regulated in the invasive process. Our results demonstrated that patients with higher RAP2 expression showed unfavourable prognoses. In vitro studies demonstrated that silencing of RAP2 inhibited the invasion of pancreatic cancer cells. Moreover, our results demonstrated that transforming growth factor-β1 (TGF-β1), an inducer of the metastatic potential of pancreatic cancer cells, regulates the expression of RAP2 via the transcription factor c-Myc. In conclusion, the present study uncovered RAP2 as a novel predictive marker and therapeutic target for pancreatic cancer

miRNA-10a-5p Targeting the BCL6 Gene Regulates Proliferation, Differentiation and Apoptosis of Chicken Myoblasts

Proliferation, differentiation, and apoptosis are three essential stages in cell development, and miRNAs can achieve extensive regulation of cellular developmental processes by repressing the expression of target genes. According to our previous RNA-seq results, miRNA-10a-5p was differentially expressed at different periods in chicken myoblasts, revealing a possible association with muscle development. In this study, we concluded that miRNA-10a-5p inhibited chicken myoblasts’ proliferation and differentiation and promoted chicken myoblasts’ apoptosis by directly targeting BCL6, a critical transcription factor involved in muscle development and regeneration. Overexpression of BCL6 significantly facilitated myoblasts’ proliferation and differentiation and suppressed myoblasts’ apoptosis. On the contrary, knockdown of BCL6 significantly repressed myoblasts’ proliferation and differentiation and induced myoblasts’ apoptosis. The results above suggest that miRNA-10a-5p plays a potential role in skeletal muscle growth, development and autophagy by targeting the BCL6 gene. We first revealed the functions of miRNA-10a-5p and BCL6 in the proliferation, differentiation, and apoptosis of chicken myoblasts

Somatic Genetic Variation in Solid Pseudopapillary Tumor of the Pancreas by Whole Exome Sequencing

Solid pseudopapillary tumor of the pancreas (SPT) is a rare pancreatic disease with a unique clinical manifestation. Although CTNNB1 gene mutations had been universally reported, genetic variation profiles of SPT are largely unidentified. We conducted whole exome sequencing in nine SPT patients to probe the SPT-specific insertions and deletions (indels) and single nucleotide polymorphisms (SNPs). In total, 54 SNPs and 41 indels of prominent variations were demonstrated through parallel exome sequencing. We detected that CTNNB1 mutations presented throughout all patients studied (100%), and a higher count of SNPs was particularly detected in patients with older age, larger tumor, and metastatic disease. By aggregating 95 detected variation events and viewing the interconnections among each of the genes with variations, CTNNB1 was identified as the core portion in the network, which might collaborate with other events such as variations of USP9X, EP400, HTT, MED12, and PKD1 to regulate tumorigenesis. Pathway analysis showed that the events involved in other cancers had the potential to influence the progression of the SNPs count. Our study revealed an insight into the variation of the gene encoding region underlying solid-pseudopapillary neoplasm tumorigenesis. The detection of these variations might partly reflect the potential molecular mechanism