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.

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.

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.

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.

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.

Recombinant Human Peroxiredoxin-5 Improves Anti-tumor Immunity by Inducing Macrophage Polarization / 中国生物化学与分子生物学报

Tumor cells can use different strategies to suppress the immune system and disable them for killing tumor cells. Previous studies have shown that recombinant human peroxiredoxin-5 (hPRDX5) can activate the normal anti-tumor immune, so as to control and eliminate the tumor cells, but its exact mechanism of action needs to be studied in depth. The study aimed to investigate whether hPRDX5 exerts its anti-tumor activity by activating or reversing the polarization state of mouse macrophages RAW264. 7 cells. The results of CCK8 showed that different doses of hPRDX5 could significantly enhance the viability of macrophage compared with the control group (P < 0. 001); The results of Nitric oxide (NO) test showed that hPRDX5 significantly enhanced NO secretion levels in RAW264. 7 cells (P < 0. 001); ELISA experiments revealed that hPRDX5 promotes TNF-α (P<0. 01) and IL-6 (P<0. 001) secretion in RAW264. 7 cells; Flow cytometry revealed that hPRDX5 increased the expression of antigen differentiation cluster (CD) 80 (P < 0. 01) and inducible nitric oxide oxide synthase (iNOS) (P < 0. 001) in RAW264. 7 cells, and reduced the expression of CD206 (P < 0. 001) in RAW264. 7 cells induced by tumor conditional culture solution (TCS); Lactate dehydrogenase (LDH) experiments revealed that hPRDX5 can increase the killing activity of mouse macrophages on mouse pancreatic cancer Panc02 cells. hPRDX5 is able to activate mouse macrophage RAW264. 7 cells, promotes its M1-type polarization, reverses M2-type polarization, and exerts antitumor activity through the immune-enhancing effect.

The Deubiquitinating Enzyme USP14 Promotes the Proliferation and Migration Ability of Pancreatic Cancer Cells / 中国生物化学与分子生物学报

Pancreatic cancer remains one of the deadliest cancer types with few effective treatment options. While the overexpression of ubiquitin-specific protease 14 (USP14) has been observed in many tumor cells, including pancreatic cancer cells, its precise role in pancreatic cancer is not well defined. Here, we investigated the biological function of USP14 in pancreatic cancer and its molecular mechanisms. Our analysis of the Cancer Genome Atlas database revealed that USP14 was highly expressed in pancreatic cancer tissues,and further investigation revealed that its expression level was negatively correlated with the prognosis of patients. In SW1990 and MIAPaCa2 pancreatic cancer cells,we established stable USP14-knockdown cell lines using the shRNA-USP14 lentivirus and found that USP14 knockdown inhibited the proliferation and migration ability of pancreatic cancer cells by CCK8, colony formation assay, wound-healing and Transwell assays. Western blotting analysis showed that downregulation of USP14 expression resulted in a decrease in CyclinD3 protein levels, while overexpression of USP14 increased the protein levels in SW1990 and MIAPaCa2 pancreatic cancer cells. Furthermore, co-immunoprecipitation demonstrated that USP14 interacts with CyclinD3 and ubiquitination assays show that overexpression of USP14 reduces the ubiquitination level of CyclinD3. Moreover, CRISPR / Cas9-mediated USP14 knockout in SW1990 pancreatic cancer cells resulted in decreased CyclinD3 protein levels. These findings suggest that USP14 promotes the proliferation and migration ability of pancreatic cancer cells by interacting with CyclinD3, highlighting USP14 as a potential therapeutic target for pancreatic cancer.

Miriplatin-loaded liposome, as a novel mitophagy inducer, suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication

Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome-lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1-Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges / 医学前沿

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.

Therapeutic Effect of Reibaisan (WTMCGEP) in Patients with Advanced Cancer / 日本東洋医学雑誌

Here we report 3 cases of advanced cancer using multidisciplinary treatment including reibaisan (WTMCGEP, a dry extract of Wisteria floribunda, Trapa natans, Myristica fragrans, Coix semen, Ganoderma lucidum, Elfvingia applanata, Punica granatum). Case 1 : 87-year-old man, suffering from stage IV esophageal squamous cell carcinoma (ESCC) with aortic and bronchial invasion, was referred to our clinic for palliative care. He had radiotherapy and chemotherapy. Only one course of chemotherapy was performed due to its intolerable side effects. The treatment with reibaisan started 11 months after the diagnosis. ESCC disappeared after 17 months of reibaisan treatment, and no relapse was observed for 66 months after the diagnosis. Case 2 : 79-year-old man, suffering from stage III ESCC, was initially scheduled for surgery after preoperative chemotherapy. Only one course of preoperative chemotherapy was performed because of its intolerable side effects. Therefore, radiotherapy combined with reibaisan followed. ESCC disappeared 6 months later, and no relapse was observed for 33 months after the diagnosis. Case 3 : 73-year-old woman, suffering from stage IV pancreatic cancer with systemic metastasis (brain, lung, and peritoneum). She initially showed Trousseau syndrome and was treated with low-molecular-weight heparin for multiple cerebral infarctions. One-month palliative chemotherapy and reibaisan resulted in a rapid reduction of ascites and improvement of neurological symptoms. Her progression-free survival period was 7 months. She lived 13 months thereafter. This suggests that reibaisan, which contains crude drugs that have been shown to have antitumor effects, may be another promising treatment for advanced cancers.

Bioinformatics analysis of survival-related genes in pancreatic cancer based on GEO and TCGA database / 西安交通大学学报(医学版)

【Objective】 Based on Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database, survival analysis was used to screen the key prognostic genes involved of pancreatic cancer patients. 【Methods】 Two pancreatic cancer gene chips (Microarray) from the GEO database and transcriptome sequencing (RNA-seq) from the TCGA database were used to filter the survival-related genes using Kaplan-Meier (KM) analysis and Cox risk model, and the target genes were intersected. Prognosis-associated genes were screened first and then pathway enrichment analysis or immune-enrichment analysis was performed based on these genes to find out their potential molecular mechanisms in regulating pancreatic cancer. 【Results】 In this study, five survival-related genes (i.e., CDO1, DCBLD2, FAM83A, ITGA3 and SLC16A3) were screened out. Multifactorial Cox regression analysis and clinical correlation analysis showed that high CDO1 expression was a protective factor for pancreatic cancer prognosis, and its antitumor effect was associated with its role in inhibiting the malignant biological behavior of pancreatic cancer cells and promoting the infiltration of immune killer cells in pancreatic cancer. 【Conclusion】 This study suggests that CDO1 is a potential tumor suppress gene of pancreatic cancer, and the tumor inhibition effect of CDO1 may be related to its role in remodeling the immune microenvironment of pancreatic cancer.

Study on the distribution of ABO blood group in patients with pancreatic cancer / 中国输血杂志

【Objective】 To investigate whether there is a correlation between the differences in ABO blood group distribution in patients with pancreatic cancer, and to evaluate the relative risk. 【Methods】 Patients with pathological diagnosis or discharge diagnosis of pancreatic cancer who underwent ABO blood group typing in our hospital from January 2017 to October 2021 were selected, and the blood group distribution of patients and the correlation were analyzed. 【Results】 There was a statistically significant difference between the pancreatic cancer group and the control group (P<0.05). The study showed that type A may be a relative risk factor for pancreatic cancer patients (χ2=42.44, P<0.001), and type B may play a protective role (χ2=16.28, P<0.01). Significant differences were found in distribution between different gender groups (χ2=64.35, P<0.05). The test results showed that type A may be a risk factor for pancreatic cancer in men (χ2=35.2, OR=1.7, 95%CI=0.59-1.02, P<0.001), and type O may play a protective role in pancreatic cancer(χ2=18.22, OR=0.6, 95%CI=0.25-0.32, P<0.01); type A may be a relative risk factor for female pancreatic cancer patients (χ2=7.06, OR=1.4, 95%CI=0.59-1.02, P<0.001), while type B may play a protective role (χ2=20.32, OR=0.5, 95%CI=0.32-0.43, P<0.01). In pancreatic cancer group, the risk factors of blood type A were higher than those of non-A group, and the protective effect of type B was significantly higher than that of non-B group. 【Conclusion】 The distribution of blood group and relative risk factors in pancreatic cancer patients suggest that A type is predominant; in the population with A blood group, more attention should be paid to early prevention and early treatment, so as to reduce the risk of disease.

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.

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.