Pancreatic cancer is a highly lethal malignancy and one of the leading causes of cancer-related death. During the development and progression of cancer, tumor angiogenesis plays a crucial role. A great deal of evidence has revealed that human mast cells (MCs) contributed to tumor angiogenesis through releasing several pro-angiogenetic factors, among which tryptase is one of the most active. However, the role of mast cell tryptase (MCT) in human pancreatic cancer angiogenesis is still not well documented. In this study, we examined the MCT levels in serum from pancreatic cancer patients and evaluated the correlationship of the MCT level and tumor angiogenesis. In addition, the effect of MCT on endothelial cell proliferation and tube formation was investigated both in vitro and in nude mice bearing pancreatic tumor. It was found that MCT contributes to endothelial cell growth and tube formation via up-regulation of angiopoietin-1 expression. Moreover, using the MCT inhibitor nafamostat, tryptase-induced angiogenesis was obviously suppressed both in vitro and in vivo. Our findings suggest that MCT plays an important role in pancreatic cancer angiogenesis and tumor growth via activating the angiopoietin-1 pathway, and tryptase inhibitors may be evaluated as an effective anti-angiogenetic approach in pancreatic cancer therapy.
Immunotherapy has become the central pillar of cancer therapy. Immune checkpoint inhibitors (ICIs), a major category of tumor immunotherapy, reactivate preexisting anticancer immunity. Initially, ICIs were approved only for advanced and metastatic cancers in the salvage setting after or concurrent with chemotherapy at a response rate of around 20–30% with a few exceptions. With significant progress over the decade, advances in immunotherapy have led to numerous clinical trials investigating ICIs as neoadjuvant and/or adjuvant therapies for resectable solid tumors. The promising results of these trials have led to the United States Food and Drug Administration (FDA) approvals of ICIs as neoadjuvant or adjuvant therapies for non-small cell lung cancer, melanoma, triple-negative breast cancer, and bladder cancer, and the list continues to grow. This therapy represents a paradigm shift in cancer treatment, as many early-stage cancer patients could be cured with the introduction of immunotherapy in the early stages of cancer. Therefore, this topic became one of the main themes at the 2021 China Cancer Immunotherapy Workshop co-organized by the Chinese American Hematologist and Oncologist Network, the China National Medical Products Administration and the Tsinghua University School of Medicine. This review article summarizes the current landscape of ICI-based immunotherapy, emphasizing the new clinical developments of ICIs as curative neoadjuvant and adjuvant therapies for early-stage disease.
One of the most prominent hematologic effects of infection with coronavirus disease 2019 (COVID-19) is increased thrombotic risk. 1,2 The mechanisms of this hypercoagulable state, which defies even therapeutic anticoagulation, are under intense investigation. Autopsy studies have confirmed thrombotic disease not only at the macrovascular scale (pulmonary emboli, venous thromboses) but also with microthrombi in alveolar capillaries and severe endothe
e16003 Background: Genomic instability from 20q amplification is an oncogenic pathway in colorectal cancer (CRC). Several genes have been implicated, including BCL2L1, AURKA, SRC, ASXL1, GNAS and TOP1. There is a lack of data regarding 20q amplified group and one study implicating these genes suggested these patients have better overall survival. Next Generation Sequencing (NGS) has become widely used in metastatic CRC (mCRC) and easily identifies patients with 20q amplification. Nevertheless, most oncologists do not routinely consider 20q amplification status and this subgroup remains underinvestigated. This study aims to investigate genomic and clinical characteristics of 20q amplified mCRC using a single-center retrospective cohort and a multi-center genomic dataset. Methods: A cohort was identified comprising patients with mCRC who had NGS testing of tumor DNA and were treated between 2014-2019. Cases with and without 20q amplification were identified. Genomic, clinical and survival data were analyzed. Significant genomic findings were compared with all-stage CRC data using the AACR Genomic Evidence Neoplasia Information Exchange (GENIE) and The Cancer Genome Atlas (TCGA) databases. Results: Of the mCRC cohort ( n= 72), 15% ( n= 11) had 20q amplification. Amplified and non-amplified groups had no significant differences in age, sex or follow-up time. Patients with 20q amplification were more likely to have never smoked, and less likely to have treatment with targeted therapy. Survival analysis showed clear separation with longer overall survival for the amplified group. Eight genes at loci 20q11 to 20q13 were amplified - in order of frequency: ASXL1, GNAS, ARFRP1, ZNF217, AURKA, BCL2L1, SRC and TOP1. 20q amplification was significantly associated with wild-type RAS and BRAF, microsatellite stability, mutant TP53 and mutant APC. Using the GENIE and TCGA databases, it was found that metastatic disease had increased prevalence of all 20q amplified genes except TOP1, when compared to all-stage CRC. Conclusions: Clinical use of NGS identifies the 20q amplification subgroup that has increased prevalence in mCRC (compared to all CRC). Compared to non-20q amplified mCRC, this group had better survival, suggesting genomic pattern in mCRC is a novel independent prognostic marker. We believe mCRC patients would benefit from further studies defining a genomic prognostication model and development of therapy targeting the 20q amplification pathway.
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