1.Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor.
Ju-Ying JIAO ; Chien-Shan CHENG ; Zhang-Qi CAO ; Lian-Yu CHEN ; Zhen CHEN
Chinese journal of integrative medicine 2024;30(1):85-95
		                        		
		                        			
		                        			Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			Hot Temperature
		                        			;
		                        		
		                        			Pancreatic Neoplasms/therapy*
		                        			;
		                        		
		                        			Models, Animal
		                        			;
		                        		
		                        			Syndrome
		                        			
		                        		
		                        	
2.Progress and reflection of conversion therapy for locally advanced pancreatic cancer.
Chinese Journal of Surgery 2023;61(7):540-545
		                        		
		                        			
		                        			With the improvement of nonsurgical treatment in pancreatic cancer, the increasing accuracy of subclassification of anatomy, and the continuous refinement of surgical resection techniques, more and more locally advanced pancreatic cancer(LAPC) patients have the opportunity to undergo conversion surgery and achieve survival benefits,which has attracted the attention of scholars in this field. Despite the numerous prospective clinical studies conducted, there is still a lack of high-level evidence-based medical evidence in terms of conversion treatment strategies, efficacy evaluation, surgical timing and survival prognosis, and there are not yet specific quantitative standards and guiding principles for conversion treatment for these patients in clinical practice, and the indications for surgical resection rely more on the experience of each center or surgeon, lacking consistency. Therefore,the indicators for the evaluation of the efficacy of conversion treatment in patients with LAPC were summarized to reflect on the different modes of conversion treatment and clinical outcomes currently being explored, expecting to provide more accurate recommendations and guidance for the clinic.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Pancreatic Neoplasms/drug therapy*
		                        			;
		                        		
		                        			Neoadjuvant Therapy
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			
		                        		
		                        	
3.Current status and prospects of neoadjuvant therapy for resectable pancreatic cancer.
Xu ZHANG ; Yong Su MA ; Xiao Dong TIAN ; Yin Mo YANG
Chinese Journal of Surgery 2023;61(7):546-549
		                        		
		                        			
		                        			Pancreatic cancer is a highly malignant tumor. About 75% of patients with pancreatic cancer who underwent radical surgical resection will still experience postoperative recurrence. Neoadjuvant therapy could improve outcomes in patients with borderline resectable pancreatic cancer,has become a consensus;however it is still controversial in resectable pancreatic cancer. Limited high-quality randomized controlled trial studies support the routine initiation of neoadjuvant therapy in resectable pancreatic cancer. With the development of new technologies, such as next-generation sequencing, liquid biopsy, imaging omics, and organoids, patients are expected to benefit from the precision screening of potential candidates for neoadjuvant therapy and individualized treatment strategy.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Neoadjuvant Therapy/methods*
		                        			;
		                        		
		                        			Pancreatic Neoplasms/pathology*
		                        			
		                        		
		                        	
4.Pay attention to whole cycle management of pancreatic cancer.
Chinese Journal of Surgery 2023;61(7):550-555
		                        		
		                        			
		                        			The prognosis for pancreatic cancer is extremely poor. To improve the prognosis of pancreatic cancer, it is urgently needed to improve early detection to advance treatment. And basically, it is also necessary to emphasise basic research to find novel therapies. By promoting the disease-centered multidisciplinary team model, researchers should achieve high-quality closed-loop process management of the entire life cycle which consists of prevention, screening, diagnosis, treatment, rehabilitation,and follow-up, with the objective of establishing a standard clinical process to improve the outcome in essence. This article summarized the progress of pancreatic cancer at different stages of the whole cycle management recently and shared the experience of pancreatic cancer treatment from the author's team in the past ten years.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Pancreatic Neoplasms/therapy*
		                        			;
		                        		
		                        			Pancreas
		                        			;
		                        		
		                        			Prognosis
		                        			
		                        		
		                        	
5.A case of pancreatic cancer treated with chemotherapy combined with immunotherapy and targeted therapy.
Bo ZHANG ; Kezhong TANG ; Xin DONG
Journal of Zhejiang University. Medical sciences 2023;52(5):578-582
		                        		
		                        			
		                        			A 68-year-old male was admitted due to fatigue and poor appetite and diagnosed pathologically as pancreatic adenocarcinoma with liver metastasis. The tumor marker carbohydrate antigen 199 (CA199) level was 2003.4 U/mL. The patient received two cycles of modified FOLFIRINOX plus immune checkpoint inhibitor (penpulimab). However, the tumor did not shrink and CA199 level was even higher. Anlotinib was added from the 3rd cycle, and the size of primary tumor and metastatic lesions were significantly reduced. Laparoscopic distal pancreatectomy and splenectomy as well as liver metastasis resection was performed. Three cycles of combined therapy were adopted after surgery followed by maintenance therapy with anlotinib plus penpulimab. There was no evidence of tumor recurrence during the follow-up (nearly 19 months since diagnosis).
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Pancreatic Neoplasms/drug therapy*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Adenocarcinoma
		                        			;
		                        		
		                        			Neoplasm Recurrence, Local/surgery*
		                        			;
		                        		
		                        			Immunotherapy
		                        			;
		                        		
		                        			Liver Neoplasms/therapy*
		                        			;
		                        		
		                        			Pancreatectomy
		                        			
		                        		
		                        	
6.Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma.
Bo NI ; Yiqing YIN ; Zekun LI ; Junjin WANG ; Xiuchao WANG ; Kaiyuan WANG
Neuroscience Bulletin 2023;39(11):1717-1731
		                        		
		                        			
		                        			Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy, characterized by late diagnosis, aggressive growth, and therapy resistance, leading to a poor overall prognosis. Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape. The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets. In this review, we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC, summarize the potential signaling pathways modulating the neuronal-cancer interaction, and discuss the current and future therapeutic possibilities for this condition.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Carcinoma, Pancreatic Ductal/pathology*
		                        			;
		                        		
		                        			Pancreatic Neoplasms/therapy*
		                        			;
		                        		
		                        			Signal Transduction
		                        			;
		                        		
		                        			Peripheral Nerves/metabolism*
		                        			;
		                        		
		                        			Tumor Microenvironment
		                        			
		                        		
		                        	
7.Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges.
Zhichen JIANG ; Xiaohao ZHENG ; Min LI ; Mingyang LIU
Frontiers of Medicine 2023;17(6):1135-1169
		                        		
		                        			
		                        			Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Pancreatic Neoplasms/therapy*
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Pancreas/pathology*
		                        			;
		                        		
		                        			Genetic Predisposition to Disease
		                        			;
		                        		
		                        			Genomics
		                        			
		                        		
		                        	
8.Study of perioperative safety of laparoscopic pancreaticoduodenectomy in elderly patients.
Daofu FENG ; Yizeng WANG ; Jizhe LI ; Baozhu LI ; Nan LI
Chinese Critical Care Medicine 2023;35(10):1063-1069
		                        		
		                        			OBJECTIVE:
		                        			To investigate the safety of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients and the related risk factors admitted to the intensive care unit (ICU) after LPD.
		                        		
		                        			METHODS:
		                        			The perioperative data of patients who underwent LPD in Tianjin Medical University General Hospital from February 2017 to June 2023 were retrospectively collected, including basic data, preoperative laboratory indicators, intraoperative and postoperative indicators, pathological results (tumor size, lymph node dissection and pathological type), postoperative complications, ICU postoperative management and prognosis. The patients were divided into the elderly group (≥ 65 years) and the non-elderly group (< 65 years) according to age. Perioperative data between two groups were compared. Kaplan-Meier survival curve was drawn to analyze the survival rate of the elderly group and the non-elderly group, and the pancreatic head carcinoma group and other type of tumors group after LPD. Logistic regression was used to analyze the risk factors of ICU stay (length of ICU stay > 1 day) after LPD in elderly patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of this risk factor for ICU stay after LPD in elderly patients.
		                        		
		                        			RESULTS:
		                        			A total of 160 patients were enrolled, including 57 cases in the elderly group (17 cases of vascular reconstruction) and 103 cases in the non-elderly group (40 cases of vascular reconstruction). All patients underwent R0 resection and were transferred to the comprehensive ICU for treatment. The follow-up time of patients with malignant tumors was 43 (6, 72) months. The elderly group had significantly longer surgery time, postoperative hospital stay and oral feeding time than the non-elderly group, and the incidence of delayed gastric emptying (DGE) was significantly higher than that in the non-elderly group. There were no significant differences in intraoperative blood transfusion rate, intraoperative blood loss, pathological results, short-term and severe postoperative complications, reoperation rate and 90-day mortality between the two groups. In patients with vascular resection reconstruction, the intraoperative blood loss in the elderly group was significantly higher than that in the non-elderly group, and the operation time and postoperative hospital stay were significantly longer. During ICU, the acute physiology and chronic health evaluation II [APACHE II: 12 (9, 14) vs. 8 (7, 10)], sequential organ failure assessment [SOFA: 6 (4, 8) vs. 3 (2, 5)] within 24 hours after admission to ICU were significantly increased in the elderly group (both P < 0.05), the time of mechanical ventilation [hours: 12 (10, 15) vs. 9 (5, 13)] and the length of ICU stay [days: 2 (1, 2) vs. 1 (1, 1)] were significantly increased in the elderly group (both P < 0.05), and the proportion of multi-disciplinary team (MDT) was also significantly increased in the elderly group (33.3% vs. 17.4%, P < 0.05), there were no significant differences in the levels of hemoglobin (Hb), albumin, and blood lactic acid between the two groups. Logistic regression analysis showed that the APACHE II score was an independent risk factor for ICU stay after LPD in elderly patients (β = 1.737, P = 0.028). ROC curve showed that the prediction performance was the best when the APACHE II score was 13, with the sensitivity of 72.41% and the specificity of 96.43%, and the area under the ROC curve (AUC) of 0.884. The Kaplan-Meier survival curve showed that there were no significant difference in median survival time (months: 24.1 vs. 24.7) and 5-year survival rate (19.01% vs. 19.02%) between the elderly group (52 cases) and the non-elderly group (92 cases) among the 144 patients with malignant tumors (both P > 0.05). The median survival time in the pancreatic head carcinoma group was significantly shorter than that in the other tumors group (63 cases; months: 20.2 vs. 40.1, P < 0.05), 5-year survival rate was significantly lower than that in the other tumors group (21.98% vs. 30.91%, P < 0.05).
		                        		
		                        			CONCLUSIONS
		                        			LPD is a safe and feasible treatment for elderly patients. APACHE II score has a certain predictive value for ICU stay after LPD in elderly patients.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Sepsis/therapy*
		                        			;
		                        		
		                        			ROC Curve
		                        			;
		                        		
		                        			Pancreaticoduodenectomy/adverse effects*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Blood Loss, Surgical
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Pancreatic Neoplasms/surgery*
		                        			;
		                        		
		                        			Postoperative Complications
		                        			;
		                        		
		                        			Intensive Care Units
		                        			
		                        		
		                        	
9.Chinese Medical Association consensus for standardized diagnosis and treatment of pancreatic neuroendocrine neoplasms.
Feng JIAO ; Jiujie CUI ; Deliang FU ; Qi LI ; Zheng WU ; Zan TENG ; Hongmei ZHANG ; Jun ZHOU ; Zhihong ZHANG ; Xiaobing CHEN ; Yuhong ZHOU ; Yixiong LI ; Yiping MOU ; Renyi QIN ; Yongwei SUN ; Gang JIN ; Yuejuan CHENG ; Jian WANG ; Gang REN ; Jiang YUE ; Guangxin JIN ; Xiuying XIAO ; Liwei WANG
Chinese Medical Journal 2023;136(20):2397-2411
10.Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway.
Yue-Hong GUAN ; Gui-Mei LIU ; Yu-Si LIU ; Lin-Bo LAN ; Rui ZHENG ; Xiao-Bin LIU
China Journal of Chinese Materia Medica 2023;48(19):5278-5284
		                        		
		                        			
		                        			This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 μmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 μmol·L~(-1)), low-concentration(10 μmol·L~(-1)) saikosaponin D, and high-concentration(16 μmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Proto-Oncogene Proteins c-akt/genetics*
		                        			;
		                        		
		                        			Caspase 3
		                        			;
		                        		
		                        			bcl-2-Associated X Protein
		                        			;
		                        		
		                        			Beclin-1/pharmacology*
		                        			;
		                        		
		                        			Cell Line, Tumor
		                        			;
		                        		
		                        			TOR Serine-Threonine Kinases/genetics*
		                        			;
		                        		
		                        			Apoptosis
		                        			;
		                        		
		                        			Pancreatic Neoplasms/drug therapy*
		                        			;
		                        		
		                        			Caspases
		                        			;
		                        		
		                        			Autophagy
		                        			
		                        		
		                        	
            
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