A meta-analysis on the efficacy of endoscopic ultrasonography for treatment of pancreatic cancer

Abstract Objective: This study aimed to systematically evaluate the efficacy and safety of Endoscopic Ultrasonography (EUS) for the treatment of pancreatic cancer. Methods: The PubMed, Embase, Web of Science, and Google Scholar databases were searched from the inception of the databases to June 2022. RevMan 5.3.0 software was utilized for data analysis. In total, 13 self-descriptive studies, which enrolled 382 patients, were finally included. Results It was revealed that EUS for the treatment of pancreatic cancer exhibited a lower incidence of adverse reactions (Relative Risk Ration [RR = 0.23], 95 % Confidence interval [95 % CI 0.23-0.23]), a higher success rate (RR = 0.90, 95 % CI 0.90-0.90), and a low failure rate (RR = 0.06, 95 % CI 0.06-0.06). Moreover, EUS-guided Celiac Plexus Neurolysis (EUS-CPN) not only significantly relieved pancreatic cancer patients' pain (RR = 0.83, 95 % CI 0.83-0.83), but also significantly eliminated pain in some patients (RR = 0.09, 95 % CI 0.09-0.09). The effects of EUS on pancreatic cancer treatment were satisfactory, and few adverse reactions were found. Conclusion: Owing to the restricted sample size in this meta-analysis, primarily consisting of descriptive studies, it was imperative to conduct more rigorously designed, multi-center, long-term follow-up, larger sample, and Randomized Controlled Trials (RCTs) to validate the findings.

Composition Spectrum of Oral Microbiota Diversity in Patients with Pancreatic Cancer: A Systematic Review / 肿瘤防治研究

Objective To systematically evaluate the diversity of oral flora in patients with pancreatic cancer. Methods A cross-sectional study was conducted, focusing on the oral flora diversity profiles of patients with pancreatic cancer. The studies were retrieved from PubMed, Web of science, EMbase, The Cochrane Library, CBM, CNKI, Wanfang, and VIP databases, and the search period was from the establishment of the database to July 15, 2023. According to the inclusion and exclusion criteria, two researchers screened intensive review literature, extracted data and information, and carried out Meta-analysis using qualitative systematic review and Review Manager 5.4. Results Seven cross-sectional studies were reviewed, including 187 patients with pancreatic cancer and 440 healthy controls. The results of meta-analysis showed that the oral microbiota diversity Simpson index of patients with pancreatic cancer was reduced compared with that of healthy controls. Qualitative analysis showed that the relative abundance of Firmicute, Prevotella, Roseburia, and Streptococcus in patients with pancreatic cancer was higher than that in healthy people. The relative abundance of Proteobacteria, Neisseria, Haemophilus, porphyromonas, and Haemophilus parainfluenza in patients with pancreatic cancer was lower than that in healthy people. Conclusion Patients with pancreatic cancer have distinct oral flora, which has high relative abundance of Firmicutes, Prevotella etc. and low relative abundance of Proteobacteria, Neisseria, etc.

Expression and Clinical Significance of MKI67 in Pancreatic Cancer / 肿瘤防治研究

Objectives To explore the expression, biological function, and mechanism of MKI67 in pancreatic cancer and its clinical significance. Methods The expression level, diagnosis, and prognostic value of MKI67 in pancreatic cancer were analyzed using public databases. We also investigated the association between the MKI67 with immune cell infiltration and immune checkpoint molecules. We analyzed the functional pathway enrichment to uncover the possible molecular mechanisms. qRT-PCR and Western blot assay were used to verify the expression of MKI67 mRNA and protein. Immunohistochemistry staining was used to detect the expression of MKI67 in tissue protein. Results The high expression of MKI67 was significantly associated with high histological grades and poor outcomes in pancreatic cancer. High MKI67 expression was correlated with poor prognosis of pancreatic cancer patients (P=0.009). MKI67 was an independent risk factor for the patient outcome (95%CI: 1.084-1.743, P<0.05). The MKI67 expression was positively correlated with the helper T cell 2 levels but negatively correlated with plasmacytoid DC, NK cells, mast cells, the T follicular helper, immune DC, and CD8 T cells. Conclusion MKI67 may serve as a biomarker for the diagnosis and prognosis of pancreatic cancer and the mechanism might be associated with immune escape or immunosuppression.

Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Factores asociados a mayor sobrevida en pacientes con cáncer de páncreas tratados mediante pancreatoduodenectomía. Estudio de casos y controles

Introducción: El cáncer de páncreas (CP) tiene un pronóstico ominoso a pesar de los avances en técnica quirúrgica y en los cuidados peri/postoperatorios. Nuestro objetivo fue identificar factores asociados a mayor sobrevida en pacientes con CP tratados mediante pancreatoduodenectomía (PD). Material y Método: Estudio de casos y controles de pacientes con CP tratados mediante PD en el Hospital Clínico de la Universidad Católica entre 2002-2015. Se definió como caso al paciente con sobrevida ≥ 3 años y como control a aquel con sobrevida inferior a ese plazo. Se comparó entre casos y controles datos biodemográficos, clínicos, histopatológicos, de morbilidad y mortalidad mediante regresión logística. Resultados: Se analizaron 70 pacientes, con una edad media de 62 ± 11 años; 40 (57%) mujeres. Hubo morbilidad en 26 enfermos (37,1%); Clavien-Dindo ≥ Illa en 8 (11,4%). La mediana (rango) de días de hospitalización fue 12 (7-84). La sobrevida actuarial a 1, 3 y 5 años fue 77%, 32% y 22% respectivamente. Se identificaron 21 casos (30%) y 49 controles (70%). En el análisis univariable, la resección R0, los ganglios regionales negativos, la ausencia de infiltración perineural, los estadios más precoces (IA, IB y IIA) y la ausencia de diabetes mellitus (DM2) al momento del diagnóstico, fueron variables asociadas a sobrevida ≥ 3 años (p 100 U/mL) y los tratamientos complementarios no se asociaron a diferencias significativas en sobrevida. En el análisis multivariable, se identificó la ausencia de DM2 (OR ajustado: 12; IC95% 1,7-84,3), la ausencia de infiltración perineural (OR ajustado: 7; IC95% 1,3-36,3) y los estadios precoces IA, IB y IIA (OR ajustado: 10,3; IC95% 2,1-49,1) como los factores independientes asociados a sobrevida mayor a 3 años. Conclusión: Los pacientes no diabéticos, con etapas precoces del CP sin infiltración perineural, resecados R0 mediante PD pueden obtener una sobrevida mayor a 3 años.

Introduction: Pancreatic cancer (PC) remains one of the most lethal malignancies, despite developments in surgical and non-surgical therapies. Significant improvements in long-term survival have not been achieved. Only radical surgical resection has obtained a moderate extension in survival. We aim to identify factors associated with longer survival in patients with PC treated by pancreatoduodenectomy (PD). Material and Method: We designed a case-control study of patients with PC treated by PD in our center between 2002-2015. We compare patients who survived ≥ 3 years (case) with those not achieving it (control). Bio-demographic, clinical, histopathological, morbidity and mortality data were compared between cases and controls using logistic regression. Results: Seventy patients were analyzed; mean age 62 ± 11 years; 40 (57%) women. Morbidity was found in 26 patients (37.1%); Clavien-Dindo ≥ Illa in 8 (11.4%). The median (range) of hospitalization days was 12 (7-84). The actuarial 1, 3, and 5 years survival was 77%, 32%, and 22%, respectively, for the entire series. Twenty-one cases (30%), and 49 controls (70%) were identified. In the univariate analysis, R0 resection, negative regional lymph nodes, the absence of perineural infiltration, the earliest stages (IA, IB, and IIA) and the absence of diabetes mellitus (DM) at time of diagnosis were variables associated with survival ≥ 3 years (p 100 U / mL), and neo/adjuvant treatments, did not significantly show differences in survival. In the multivariate analysis, no DM at diagnosis (adjusted OR: 12; 95% CI 1.7 - 84.3), no perineural infiltration (adjusted OR: 7; 95% CI 1.3 - 36.3) and early stages IA, IB, and IIA (adjusted OR: 10.3; 95% CI 2.1 - 49.1) were identified as independent factors associated with survival > 3 years. Conclusion: Nondiabetic patients with early stages PC without perineural infiltration, resected R0 by PD can achieve survival over 3 years.

Metástasis pulmonares aisladas de adenocarcinoma ductal de páncreas: una población con supervivencia prolongada / Isolated pulmonary metastases from pancreatic ductal adenocarcinoma: a population with prolonged survival

RESUMEN La incidencia de metástasis pulmonares aisladas en adenocarcinoma ductal de páncreas es aproximadamente del 13%. La resección de estas metástasis es infrecuente; sin embargo, los pacientes que se presentan únicamente con metástasis pulmonares tienen una mejor supervivencia comparadas con otras localizaciones. Presentamos el caso de una paciente a quien se le realizó una lobectomía pulmonar por metástasis de adenocarcinoma ductal de páncreas. Luego de la resección, el período libre de recurrencia y la supervivencia libre de enfermedad específica fueron de 84 y 152 meses, respectivamente. Consideramos que el siguiente paso en el tratamiento de esta subpoblación es poder seleccionar a los pacientes con una biología tumoral favorable y que una estrategia de tratamiento enérgica estaría justificada.

ABSTRACT The incidence of isolated pulmonary metastases in pancreatic ductal adenocarcinoma is about 13%. Resection of these metastases is uncommon; however, patients presenting only with pulmonary metastases have better survival compared to those with metastases on other locations. We report the case of a female patient who underwent lobectomy for metastases from pancreatic ductal adenocarcinoma. After resection, disease-free interval and specific diseases-free survival were 84 and 152 moths, respectively. We consider that the next step in the treatment of this subpopulation of patients is to select those patients with favorable tumor biology who would benefit from a more aggressive approach.

Comportamiento clínico-epidemiológico de los tumores periampulares malignos diagnosticados en Gastroenterología

Introducción: Los tumores malignos ubicados en la región periampular pueden ser: ampular, biliar, pancreático o duodenal, y constituyen un problema de salud por su alta mortalidad. En su etiopatogenia se involucran múltiples factores de riesgo, cuyo comportamiento clínico y epidemiológico se desconoce en la población matancera. Objetivo: Determinar el comportamiento clínico y epidemiológico de los tumores periampulares malignos. Materiales y métodos: Se realizó un estudio descriptivo, prospectivo en 34 pacientes con diagnóstico de tumores periampulares malignos, atendidos en el Servicio de Gastroenterología del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas, de enero a diciembre de 2021. Se estudiaron variables como: grupos de edad, sexo, factores de riesgo y antecedentes patológicos personales, tiempo de evolución de los síntomas y localización del tumor. Los resultados fueron recogidos en una planilla de recolección de datos. Resultados: Predominó el sexo masculino y el grupo de 50 a 69 años. Los factores de riesgo más frecuentes fueron el consumo de café, tabaquismo y diabetes mellitus. El íctero fue el síntoma más frecuente. La mayoría de los pacientes iniciaron los síntomas de 1 a 3 meses antes del diagnóstico. El cáncer de páncreas fue el más frecuente. Conclusiones: Los tumores periampulares predominaron en la población mayor de 50 años. Los hábitos tóxicos fueron los factores de riesgo más frecuentes. El cáncer de páncreas tuvo mayor incidencia. El comportamiento clínico estuvo relacionado con la localización de la lesión, el tiempo de evolución de los síntomas, y los factores de riesgo que predominaron.

Introduction: Malignant tumors located in the periampullary region can be ampullary, biliary, pancreatic or duodenal and are a health problem due to their high mortality. Their etio-pathogenesis involves many risk factors, whose clinic and epidemiological behavior is unknown by the population of Matanzas. Objective: To determine the clinical-epidemiological behavior of malignant periampullary tumors. Materials and methods: A descriptive, prospective study was conducted in 34 patients with diagnosis of malignant periampullary tumors, treated in the Gastroenterology Service of the Clinical-Surgery University Hospital Comandante Faustino Perez Hernandez, of Matanzas, from January to December 2021. Variables such as age group, sex, risk factors and personal pathological history, time of evolution of symptoms and tumor location were studied. The results were collected in a data collection form. Results: Male sex and the 50-69 years age group predominated. The most frequent risk factors were coffee consumption, smoking and diabetes mellitus. Jaundice was the most frequent symptom. Most of the patients started symptoms one to three months before the diagnosis. Pancreatic cancer was the most frequent. Conclusions: Periampullary tumors predominated in the population older than 50 years. Toxic habits were the most common risk factors. Pancreatic cancer had a higher incidence. Clinical behavior was related to the location of the lesion, the time of evolution of the symptoms, and the risk factors that predominated.

Manejo de los tumores periampulares malignos en pacientes evaluados en consulta multidisciplinaria

Introducción: Los tumores malignos ubicados en la región periampular pueden ser: ampular (carcinoma ampular), biliar (colangiocarcinoma), pancreático (tumores de la cabeza del páncreas) o duodenal (cáncer de la segunda porción duodenal), y constituyen un problema de salud por su alta mortalidad, y un motivo frecuente de consulta multidisciplinaria por oncología digestiva. Objetivo: Describir los procederes diagnósticos y resultados histopatológicos asociados al manejo de tumores periampulares en pacientes atendidos en consulta multidisciplinaria. Materiales y métodos: Se realizó un estudio descriptivo y prospectivo en 34 pacientes con diagnóstico de estas neoplasias, en el Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández. La fecha comprende de enero a diciembre del año 2021. Se estudiaron variables como: grupos de edad, sexo, resultados imagenológicos, endoscópicos e histológicos, vía para la realización de la biopsia y tratamiento definitivo. Los resultados fueron recogidos en una planilla de recolección de datos. Resultados: Predominaron el sexo masculino y el grupo de 50 a 69 años. La tomografía axial computarizada abdominal mostró mayor sensibilidad en el diagnóstico respecto al ultrasonido. La colangiopancreatografía endoscópica retrograda fue el método diagnóstico y terapéutico más utilizado, seguido del tratamiento quirúrgico paliativo. Conclusiones: El manejo de los tumores, al igual que su tratamiento definitivo, estuvo relacionado con su localización. Como todos no pudieron ser estadificados, fue necesario el estudio histológico.

Introduction: Malignant tumors located in the periampullary region may be: ampullary (ampullary carcinoma), biliary (chollangiocarcinoma), pancreatic (tumors of the pancreas head) or duodenal (cancer of the second duodenal portion). They constitute a health problem due to their high mortality and a reason of frequent multidisciplinary consultation by digestive oncology. Objective: To describe the diagnostic procedures and the histopathological results associated to the management of periampullary tumors in patients treated in multidisciplinary consultations. Materials and methods: A descriptive and prospective study was conducted in 34 patients diagnosed with these neoplasms at the Clinical-Surgical University Hospital Comandante Faustino Perez. The date ranges from January to December 2021. Variables such as age groups, sex, imaging, endoscopic and histological results, pathway for biopsy and definitive treatment were studied. The results were collected in a data collection form. Results: Male sex and the age group from 50 to 69 years predominated. Abdominal computed axial tomography showed higher sensitivity in the diagnosis than ultrasound. Retrograde endoscopic cholangiopancreatography was the most widely used diagnostic and therapeutic method, followed by palliative surgical treatment Conclusions: The management of the tumors, as well as their definitive treatment, was related to their location. Since all of them could not be staged, histological study was necessary.

Hallazgos clínicos, epidemiológicos, histológicos y anatómicos en pacientes adultos con diagnóstico de cáncer de páncreas / Clinical, Epidemiological, Histological and Anatomical Findings in Adult Patients Diagnosed with Pancreatic Cancer

Introducción: El cáncer de páncreas constituye un problema de salud debido al diagnóstico tardío, su agresividad biológica y la ausencia de un tratamiento sistémico efectivo. Objetivo: Caracterizar clínica, epidemiológica, histológica y anatómicamente a pacientes con cáncer de páncreas. Métodos: Se realizó un estudio descriptivo de casos clínicos, en pacientes con cáncer de páncreas que acudieron al Hospital Oncológico Conrado Benítez; de Santiago de Cuba, en el período comprendido diciembre 2017 hasta diciembre 2018. El universo estuvo conformado por el total de los pacientes de ambos sexos, cuya cifra ascendió a 19 que cumplieron con los criterios de inclusión. Resultados: No existió predominio significativo según el sexo, prevaleció el grupo de edades entre 61-70 años en un 31,6 por ciento, el 84,2 por ciento de los pacientes presentó como factor de riesgo la dieta rica en grasas y pobre en verduras y el tabaquismo, en el 63,2 por ciento coexistió la hipertensión arterial, la pérdida de peso fue el signo que sobresalió en el 79,0 por ciento. El 47,4 por ciento se les diagnosticó adenocarcinoma poco diferenciado, siendo la localización más frecuente de los tumores (31,6 por ciento) la cabeza del páncreas. Conclusiones: El cáncer de páncreas es una enfermedad maligna que se relacionada con la edad y sus síntomas se manifiestan tardíamente, se asocia con la presencia de factores de riesgo por lo que es necesario identificarlos precozmente, modificarlos y/o atenuarlos(AU)

Introduction: Pancreatic cancer constitutes a health problem due to late diagnosis, its biological aggressiveness and the absence of effective systemic treatment. Objective: To clinically, epidemiologically, histologically and anatomically characterize patients with pancreatic cancer. Methods: A descriptive study of clinical cases was carried out in patients with pancreatic cancer who attended the Conrado Benítez; Oncological Hospital of Santiago de Cuba, in the period from December 2017 to December 2018. The universe was made up of the total number of patients of both genders, which amounted to 19 meeting the inclusion criteria. Results: There was no significant predominance according to gender, the age group between 61-70 years prevailed in 31.6 percent, 84.2 percent of patients presented as risk factor the diet rich in fat and poor in vegetables and smoking, in 63.2 percent coexisted arterial hypertension, weight loss was the sign that stood out in 79.0 percent. The 47.4 percent were diagnosed with poorly differentiated adenocarcinoma, being the pancreatic head the most frequent location of the tumors (31.6 percent). Conclusions: Pancreatic cancer is an age-related malignant disease and its symptoms manifest late that is associated with the presence of risk factors, so it is necessary to identify them early, modify and/or attenuate them(AU)

Octreotide and postoperative pancreatic fistula after pancreaticoduodenectomy: What we know so far? A narrative review

Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used by pancreatic surgeons worldwide after pancreatic resections, often as per surgeon抯 discretion, to prevent POPF especially in cases at high risk of developing POPF. We herein analyze the data available till date of the subject. A PubMed search with keywords 搒omatostatin OR octreotide OR somatostatin analogues AND postoperative pancreatic fistula� was made. Further filters were applied in the search 揅linical Trial, Meta?Analysis, Randomized Controlled Trial, Systematic Review, from 1990 � 2021,� and the 68 results thus obtained were analyzed and included in this narrative review. There is considerable heterogeneity among the studies assessing the role of octreotide in the prevention of POPF making data comparison difficult, and hence results remain inconclusive. Most of the earlier studies used different definitions of POPF and other complications; included patients with varied pancreatic pathologies such as cancer, chronic pancreatitis, and benign lesions; surgical techniques such as pancreaticoduodenectomy, distal pancreatectomy, and other procedures; use of somatostatin and its analogs such as octreotide, lanreotide, pasireotide, and vapreotide; varied surgeon and institutional volume; and so on. Besides, pancreatic surgery is per se a complex surgical procedure and has its own inherent biases related to patient and the pancreas itself affecting the overall outcome. Data indicate favorable role of newer somatostatin analogs, and further studies are urgently needed. The question about the efficacy of prophylactic octreotide to reduce POPF after pancreaticoduodenectomy remains open to debate

Modified FOLFIRINOX compared to Gemcitabine & nab-Paclitaxel in advanced pancreatic ductal adenocarcinoma - results of a match-pair analysis

Background & objectives: FOLFIRINOX and gemcitabine plus nab-paclitaxel (GN) are the most commonly used regimens in advanced pancreatic ductal adenocarcinomas (PDACs). As there is limited data on comparison of these two regimens, the present study was aimed to compare survivals and tolerance for both regimens through a match-pair analysis. Methods: The data of 350 patients with metastatic and locally advanced PDAC, treated between January 2013 and December 2019, were retrieved. A 1:1 matching, using age and performance status, without replacement was performed by using nearest neighbour matching method. Results: A total of 260 patients (130 modified FOLFIRINOX and 130 GN) were matched. The median overall survival (OS) was 12.98 months [95% confidence interval (CI) 7.257-8.776 months] in modifications of FOLFIRINOX (mFOLFIRINOX) cohort and 12.06 months (95% CI 6.690-8.88 months) in GN group (P=0.080). The incidence of grade 3 and 4 infections, diarrhoea, oral mucositis, and fatigue was higher with mFOLFIRINOX. Patients who received second line therapy had improved OS as compared to those who did not (14.06 vs. 9.07 months, P<0.001). Interpretation & conclusions: GN and mFOLFIRINOX appear to have similar survival outcomes in an unselected match paired patient population with advanced PDAC. A markedly increased incidence of non-myelosuppressive grade 3 and grade 4 side-effects and lack of survival improvements suggest a need for nuanced use of the mFOLFIRINOX regimen. Administration of second-line chemotherapy improves OS in patients with advanced PDAC.

Current status changing trend and influencing factors of pancreatic cancer disease burden in Chengde of Hebei Province in 2010 - 2020 / 公共卫生与预防医学

Objective To analyze the disease burden status, trends and possible influencing factors of pancreatic cancer in Chengde of Hebei from 2010 to 2020, in order to provide theoretical basis for the preventionof pancreatic cancer. Methods Using the global burden of disease open database, the incidence rate, mortality, years of life lost (YLL), years of life lost with disability (YLD) and disability adjusted life year (DALY) of pancreatic cancer in the region are obtained,average annual percent change (AAPC) was calculated using joinpoint model to test the trend of disease burden change of pancreatic cancer patients from 2010 to 2020. At the same time, the patient characteristics such as hypertension, diabetes and other categorical variables were set as dummy variables, and the risk factors affecting the mortality of patients with pancreatic cancer were analyzed by linear regression. Results In 2010, there were 15 new cases of pancreatic cancer and 13 deaths in Chengde District , Hebei Province. The YLLs caused by pancreatic cancer accounted for 70.67% of DALY. In 2020, there were 160 new cases of pancreatic cancer and 147 deaths in Chengde, Hebei Province. The YLLs caused by pancreatic cancer accounted for 96.02% of DALY. From 2010 to 2020, the incidence of pancreatic cancer increased by 9.79%, and the incidence rate increased by 7.81%, showing an obvious upward trend (APCC =2.20%, P 28.0 and pancreatitis (OR=1.574 , 95% CI: 1.328-3.045) were all risk factors for death of patients with pancreatic cancer (OR>1) . Conclusion From 2010 to 2020, the incidence and mortality of pancreatic cancer among local residents in Chengde of Hebei showed an upward trend, and the disease burden was also increasing year by year. The basic diseases of diabetes and chronic pancreatitis increase the death risk and should be protected.

Study progress on traditional Chinese medicine monomer intervening in pancreatic cancer by regulating PI3K/Akt signaling pathway / 中国药房

Pancreatic cancer is one of the most destructive malignant tumors； the pathogenesis of this disease is complex and is closely related to genetic susceptibility， chronic pancreatitis， and gene mutations in signaling pathways. The phosphoinositide 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway is a classical cancer signaling pathway that is aberrantly activated in pancreatic cancer cells. In recent years， it has been found that traditional Chinese medicine （TCM） monomers show special activity in the treatment of pancreatic cancer and can be potential drug for the treatment of pancreatic cancer. Based on PI3K/Akt signaling pathway， this paper summarizes the mechanism of TCM monomer intervening in pancreatic cancer and finds that TCM monomer of alkaloids （sinomenine， dictamnine， dauricine， etc.）， terpenoids （saikosaponin A， linderalactone， isoalantolactone， etc.）， phenols （6-gingerol， curcumin， pterostilbene， etc.）， flavonoids （fisetin， kaempferol， quercetin， etc.） and quinones （β-hydroxyisovaleryl shikonin， rhein， lucidone， etc.） can inhibit the proliferation， invasion and migration of pancreatic cancer cells， regulate autophagy and apoptosis， and then inhibit the pathological process of pancreatic cancer by inhibiting PI3K/Akt signaling pathway.

Effects of PRPF19 Knockdown on Proliferation, Migration and Invasion of Pancreatic Cancer Cells / 肿瘤防治研究

Objective To investigate the effects of PRPF19 knockdown on the proliferation, migration, and invasion of pancreatic cancer cells. Methods The expression of PRPF19 in pancreatic cancer and normal tissues was analyzed using the GEPIA database. The protein and mRNA expression levels of PRPF19 in pancreatic cancer cells were detected by Western blot and qRT-PCR. Small interfering RNA (siRNA) was used to silence the expression of PRPF19 in pancreatic cancer cells, and the knockdown efficiency was verified by Western blot and qRT-PCR. CCK-8, colony forming, and Transwell assay were used to detect the effects of knockdown of PRPF19 on the proliferation, colony forming, migration, and invasion of pancreatic cancer cells. Results GEPIA analysis showed that PRPF19 was highly expressed in pancreatic cancer tissues compared with normal pancreatic tissues. In comparison with normal pancreatic cells, PRPF19 was highly expressed in various pancreatic cancer cell lines such as MIA PaCa-2 and PANC-1 (P < 0.05). In comparison with the control group, PRPF19 knockdown significantly reduced the proliferation rate, colony forming, cell migration, and invasion of pancreatic cancer cells (P < 0.05). Conclusion PRPF19 knockdown inhibits the proliferation, migration, and invasion of pancreatic cancer cells. PRPF19 may play an important role as an oncogene of pancreatic cancer.

OASL Expression in Pancreatic Cancer and Its Effect on Proliferation and Migration of Pancreatic Cancer Cells / 肿瘤防治研究

Objective To explore the effect of OASL expression on the proliferation and migration of pancreatic cancer cells. Methods The GEPIA database was used to analyze the differences in OASL expression in pancreatic cancer tissues and normal pancreatic tissues. The TIMER database was used to analyze the relationship between OASL expression and patient survival. The TCGA database was used to analyze the correlation of OASL expression with the clinicopathological parameters of pancreatic cancer. shRNA was used to knock down the expression of OASL gene in pancreatic cancer panc-1 cells. Lentiviruses were used to overexpress the OASL gene in pancreatic cancer cells. MTT assay was used to evaluate their proliferation ability, and scratch and Transwell experiments were used to evaluate their migration ability. Western blot experiments were used to detect changes in proteins related to tumor proliferation, migration, and invasion. Results OASL expression in the pancreatic cancer group was significantly higher than that in normal pancreatic tissue (P < 0.05), and patients with high OASL expression in pancreatic cancer patients had worse OS than patients with low expression (P < 0.05). After OASL gene knockdown, the proliferation and migration abilities of panc-1 cells were inhibited, whereas the overexpression of OASL gene promoted the proliferation and migration ability of panc-1 cells. Western blot experiments showed that after OASL knockdown, p-STAT3 protein expression increased, whereas STAT3 and BAK protein expressions decreased. After OASL overexpression, p-STAT3 protein expression decreased, and STAT3 and BAK protein expression increased. Conclusion OASL may affect the proliferation and migration of pancreatic cancer cells through the STAT3 signaling pathway while affecting BAK expression to induce cell death.

Inhibitory effects of gemcitabine hydrochloride combined with ferroptosis inducers on the proliferation of PANC-1 cells / 药学实践杂志

Objective To study the effects of three ferroptosis inducers Erastin (Era), sulfasalazine (SASP) and artesunate (Art) alone or combined with gemcitabine hydrochloride (hcGEM) on the proliferation inhibition of Human pancreatic cell line PANC -1. Methods The CCK-8 method was used to detect the inhibitory effects of different concentrations of Era, SASP and Art alone or combined with hcGEM on the proliferation of PANC-1, and the combination index (CI) was used to judge whether three ferroptosis inducers combined with hcGEM had synergistic inhibitory effect on PANC-1. Results The three ferroptosis inducers and hcGEM alone or in combination could significantly inhibit the activity of PANC-1. The inhibitory effects were enhanced with the concentration increasing. The CI values of hcGEM-Era 4∶1 or 1∶4 combination group and hcGEM-SASP 1∶400 combination group were less than 1.The CI values of hcGEM-Art 1∶4 or 1∶16 combination group were less than 1 only within a certain concentration range. Conclusion The inhibitory effects of the three ferroptosis inducers and hcGEM alone or in combination were dose-dependent. The combination of hcGEM and three ferroptosis inducers could synergistically inhibit the proliferation of PANC-1.

Research on the anti-tumor effect of nordihydroguaiaretic acid targeting MyD88 / 药学学报

This study mainly explores the role of myeloid differentiation primary response protein 88 (MyD88) in tumorigenesis and development, to identify active compounds targeting MyD88. CRISPR/Cas9 system and xenograft tumor model were used to detect the effect of MyD88 deletion on tumor growth, and the experimental animal ethics review number was PZSHUTCM200828006. Microscale thermophoresis technology (MST) was used to identify compounds directly bind to MyD88 and further detect the impact of candidate small molecules on cell proliferation. Results showed that depletion of MyD88 significantly inhibited xenograft tumor growth of colon cancer, pancreatic cancer and skin cancer and the activity of NF-κB signaling pathway. MST showed that nordihydroguaiaretic acid (NDGA) bound to MyD88, with the binding dissociation constant Kd of 14.61 µmol·L-1. NDGA inhibited NF-κB reporting system activation and phosphorylation of p65, the key factor in NF-κB signal pathway. In addition, the results of colony formation assay showed that NDGA suppressed the proliferation of tumor cells. The above results show that, MyD88 is a potential therapeutic target for colon cancer, pancreatic cancer and skin cancer, NDGA directly binds to MyD88 and inhibits the activity of NF-κB signaling pathway, as well as inhibits the proliferation of pancreatic cancer, skin cancer and colon cancer cells.

Progress on targets and therapeutic drugs for pancreatic cancer / 药学学报

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

Research progress on the effect mechanism of polysaccharides against pancreatic cancer / 中国药房

Polysaccharide is a recognized immunomodulator that has been shown to have inhibitory effects on a variety of cancer cells and has the potential to be developed as an anti-cancer drug. Pancreatic cancer， one of the cancers with the highest mortality rate， is treated with long-term chemotherapeutic drugs and is prone to a variety of side effects such as immune deficiency， fatigue， and neurological lesions. The polysaccharide anti-pancreatic cancer research landscape both domestically and internationally is summarized in this publication. By regulating nuclear factor-κB， Hippo-Yes-associated protein， integrin and other signaling pathways， polysaccharide components play an anti-pancreatic cancer role by multi-target ways， such as inducing apoptosis and autophagy， inhibiting proliferation， migration and invasion of cancer cells， and regulating the cancer cell cycle.

A case of pancreatic cancer treated with chemotherapy combined with immunotherapy and targeted therapy / 浙江大学学报·医学版

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).