Pancreatic Cancer Low White Blood Cell Count – Combined effects of curcumin, lycopene, or bixin in yogurt inhibit LDL oxidation and increase HDL and paraoxonase levels in streptozotocin-diabetic rats.

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Pancreatic Cancer Low White Blood Cell Count

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Pancreatic Cancer: A Review Of Epidemiology, Trend, And Risk Factors

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Detection of circulating tumor cells in pancreatic cancer using a negative enrichment immunofluorescence and in situ hybridization system.

Educational Case: Pancreatic Adenocarcinoma: Clinical Presentation, Pathogenesis, Diagnostic, And Therapeutic Modalities

By Yu Xu Yu Xu Scilit Preprints.org Google Scholar View Publications †, Tai Qin Tai Qin Scilit Preprints.org Google Scholar View Publications org Google Scholar View Publications , Chuntao Gao Chuntao Gao Scilit Preprints.org Google Scholar View Publications Preprints.org Google Scholar View Publications, Song Gao Song Gao Scilit Preprints

Pancreatic Cancer Division, Key Laboratory of Cancer Prevention and Therapy, Cancer National Clinical Research Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

Submission received: 16 January 2017 / Revised: 5 March 2017 / Accepted: 7 March 2017 / Published: 23 March 2017

Pancreatic cancer (PC) is the most lethal form of gastrointestinal cancer, and early detection and surveillance are urgent issues. Circulating tumor cells (CTCs) are emerging as a non-invasive biomarker for tumor detection. However, the low sensitivity of the conventional CellSearch system for detecting CTCs is a major problem, especially in patients with PC. In this study, we used negative enrichment (NE), immunofluorescence, and in situ hybridization (FISH) of chromosome 8 (NE-iFISH) to capture and identify CTCs in PC patients. We showed that the NE-iFISH system exhibited a dramatically higher detection rate of CTCs in PC patients (90%). The diagnostic rate of PC was 97.5% when combining CTCs ≥2 and carbohydrate antigen 19-9 (CA19-9) > 37 µmol/L. The 1-year survival in the group of CTCs < 3 was significantly higher than that of CTCs ≥ 3 (p = 0.043). Furthermore, we analyzed the role of chromosomal instability in the detection of CTCs. The group of triploid (three hybridization signals of chromosome 8) CTCs ≥ 3 showed better 1-year survival (p = 0.0279) and overall survival (p = 0.0188) than the group with triploid CTCs < 3. Importantly, triploid CTC number mean overall CTC counts chemo -Not predictive of sensitivity. Moreover, circulating tumor microembolus (CTM) was detected in stage IV patients and was positively correlated with poor response to chemotherapy. In conclusion, the NE-iFISH system significantly improved the positive detection rate of CTCs, and triploid CTC can be used to predict prognosis or response to chemotherapy of PC patients. CTM is a potential indicator of chemotherapeutic effect in advanced PC patients.

New Onset Diabetes: An Early Sign Of Pancreatic Cancer?

Pancreatic cancer (PC) is considered a lethal malignancy with a low 5-year survival rate (<5%) [ 1 , 2 ]. Due to the latent nature of symptoms, early diagnosis is still a challenge in pancreatic cancer treatment, and only 15%–20% of patients with pancreatic cancer are considered to have resectable disease when first diagnosed [ 3 ]. Currently, the gold standard for diagnosis is still pathologic examination, in which ultrasound-guided fine-needle biopsy is commonly used to obtain tissue specimens. However, the invasive procedure may cause unexpected complications including infection, bleeding, pancreatic fistula, bile leakage, etc. Furthermore, the sensitivity of imaging-guided biopsy tests for pancreatic cancer is only 80%. displacement Currently, carbohydrate antigen 19-9 (CA19-9) is the most popular biomarker and is commonly used as a prognostic indicator in pancreatic cancer patients [ 4 , 5 ]. However, the sensitivity and specificity of CA19-9 for the diagnosis of pancreatic cancer are still in doubt. Pancreatic emptying diseases, chronic pancreatitis and cholangitis have also been reported to cause increased CA19-9 levels [6]. In contrast, PC patients with a negative Lewis antigen may have normal CA19-9 levels. Therefore, there is an urgent need to find a sensitive and specific non-invasive diagnostic approach for PC.

Circulating tumor cells (CTCs) are tumor cells that shed from the solid tumor mass and travel into the peripheral circulation, which are popularly detected by the cell search system and used as promising biomarkers for monitoring chemotherapeutic efficacy in prostate cancer and breast cancer. and colon cancer [7, 8, 9]. Detection of CTCs by the CellSearch system depends on the expression of epithelial cell adhesion molecule (EpCAM) and cytokeratins (CK) on the surface of CTCs. However, the expression of EpCAM and some CKs in CTCs is significantly attenuated during the process of epithelial to mesenchymal transition (EMT) in PC [ 10 , 11 ]. Therefore, the cell search system, which has a low detection rate of CTCs, may miss CTCs [ 12 , 13 ]. Currently, negative enrichment combined with immunofluorescence and in situ chromosomal hybridization (NE-iFISH) for detection of CTCs are reported to be effective in advanced gastric cancer [14]. Since this mechanism is independent of the expression of an epithelial marker of CTCs, it is reasonable to introduce it for the detection of CTCs in PC patients. Aneuploidy is the most common hallmark of human solid tumors and is mostly caused by chromosomal instability (CIN). Replication stress induced by chromosomal gain in the nucleus can lead to genomic instability (GIN), which contributes to tumorigenesis [ 15 , 16 , 17 , 18 ]. Aneuploidy is positively associated with intrinsic or acquired chemotherapeutic drug resistance [15, 19, 20, 21]. Aneuploidy was reported as an independent marker for colon cancer recurrence [22]. More importantly, it was also reported that aneuploidy in CTCs is associated with poor overall survival and progression-free survival in lung cancer, breast cancer, ovarian cancer, and oral cancer [ 22 , 23 , 24 ].

In our study, we used the NE-iFISH system to measure aneuploidy in CTCs from PC patients and dynamically monitored CTCs during the chemotherapy process in PC patients. We explored the sensitivity and specificity of the combination of CA19-9 and CTCs determined by the NE-iFISH system in the diagnosis of pancreatic cancer.

Characteristics of the 40 PC patients and 43 control cohorts included in this study are shown in Table 1. PC patients included 25 males and 15 females; The median age at diagnosis was 59 years (62 years for men and 58 years for women). Twenty-four tumor masses were located in the head of the pancreas, and 16 samples were located in the body and tail of the pancreas. Patients were divided into two clinical groups: (1) eleven patients with resectable cases (4 patients as stage І, 7 patients as stage II); (2) Twenty-nine patients with locally advanced disease (5 patients as stage III) or metastatic lesions (24 patients as stage IV). The control group consisted of 43 individuals, including 35 healthy donors and 8 patients with pancreatic benign disease (3 cystadenocarcinoma, 1 autoimmune pancreatitis, 3 pancreatic intraductal papillary mucinous neoplasms, and 1 acute pancreatitis). Due to the benign nature of pancreatic lesions, 8 patients were included in the control cohort.

Liquid Biopsy Approach To Pancreatic Cancer

Five cell lines (Bxpc-3, PANC-1, A549, SW480, and SK-BR3) were used to evaluate the stability of this electron microscope. Outcome assessment was performed by experienced technicians; Three successive parallel judgments of the result were also determined using a microscope (Table 2). Cells were detected by NE-iFISH system and identified by automatic microscope (Figure 1). The result showed that CTC counting by electronic microscope was more stable, objective and repeatable than artificial counting.

2.3 Definition of Circulating Tumor Cells (CTC) by Negative Enrichment Immunofluorescence and In Situ Hybridization (NE-iFISH) System

The

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