scholarly journals Early detection of biomarkers for circulating tumor cells in Bone marrow and Peripheral blood in a fast-progressing gastric cancer model

2020 ◽  
Author(s):  
Prerna Bali ◽  
Ivonne Lozano-Pope ◽  
Collin Pachow ◽  
Marygorret Obonyo

AbstractHelicobacter pylori poses one of the greatest risks for development of gastric cancer. We previously established a crucial role for myeloid differentiation primary response 88 (MyD88) in the regulation of Helicobacter-induced gastric cancer. Mice deficient in Myd88 rapidly progressed to neoplasia when infected with H. felis, a close relative of H. pylori. For this study we examined circulating tumor cells (CTCs) by measuring expression of cytokeratins, epithelial to mesenchymal transition (EMT) and cancer stem cell (CSC) markers in in the bone marrow and peripheral blood of gastric cancer models we termed fast (Myd88-/-)- and slow (WT)-“progressors”. We detected cytokeratins CK8/18 as early as 3 months post infection in the fast “progressors”. In contrast, cytokeratins were not detected in slow “progressor” gastric cancer model even after 7 months post infection. Expression of MUC1 was observed in both bone marrow and peripheral blood at different time points suggesting its role in gastric cancer metastasis. Snail, Twist and ZEB were expressed at different levels in bone marrow and peripheral blood. Expression of these EMT markers suggests manifestation of cancer metastasis in the early stages of disease development. Lgr5, CD44 and CD133 were the most prominent CSC markers detected. Detection of CSC and EMT markers along with cytokeratins does reinforce their use as biomarkers for gastric cancer metastasis. This early detection of markers suggests that CTCs leave primary site even before cancer is well established. Thus, cytokeratins, EMT, and CSCs could be used as biomarkers to detect aggressive forms of gastric cancers. This information will be important in stratifying patients for treatment before the onset of severe disease characteristics.

2021 ◽  
Vol 58 (3) ◽  
pp. 388-396
Author(s):  
Prerna Bali ◽  
Ivonne Lozano‑Pope ◽  
Collin Pachow ◽  
Marygorret Obonyo

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Pengjie Yu ◽  
Shengmao Zhu ◽  
Yushuang Luo ◽  
Ganggang Li ◽  
Yongqiang Pu ◽  
...  

Objective. To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. Results. Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage ( P < 0.05 ), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy ( P < 0.05 ). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy ( P = 0.119 ). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower ( P = 0.045 ). Conclusions. Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.


Blood ◽  
1994 ◽  
Vol 83 (3) ◽  
pp. 636-640 ◽  
Author(s):  
W Brugger ◽  
KJ Bross ◽  
M Glatt ◽  
F Weber ◽  
R Mertelsmann ◽  
...  

Abstract Peripheral blood progenitor cells (PBPCs) are increasingly used for autografting after high-dose chemotherapy. One advantage of PBPCs over the use of autologous bone marrow would be a reduced risk of tumor-cell contamination. However, the actual level of tumor cells contaminating PBPC harvests is poorly investigated. It is currently not known whether mobilization of PBPCs might also result in mobilization of tumor cells. We evaluated 358 peripheral blood samples from 46 patients with stage IV or high-risk stage II/III breast cancer, small cell (SCLC) or non- small cell (NSCLC) lung cancer, as well as other advanced malignancies for the detection of epithelial tumor cells. Monoclonal antibodies against acidic and basic cytokeratin components and epithelial antigens (HEA) were used in an alkaline phosphatase-anti-alkaline phosphatase assay with a sensitivity of 1 tumor cell within 4 x 10(5) total cells. Before initiation of PBPC mobilization, circulating tumor cells were detected in 2/7 (29%) patients with stage IV breast cancer and in 2/10 (20%) patients with extensive-disease SCLC, respectively. In these patients, an even higher number of circulating tumor cells was detected after chemotherapy with VP16, ifosfamide, and cisplatin (VIP) followed by granulocyte colony-stimulating factor (G-CSF). This approach has previously been shown to be highly effective in mobilizing PBPCs. In the 42 patients without circulating tumor cells during steady state, tumor cells were mobilized in 9/42 (21%) patients after VIP+G-CSF induced recruitment of PBPCs. The overall incidence of tumor cells varied between 4 and 5,600 per 1.6 x 10(6) mononuclear cells analyzed. All stage IV breast cancer patients and 50% of SCLC patients were found to concomitantly mobilize tumor cells and PBPCs. Kinetic analyses showed two patterns of tumor cell recruitment depending on the presence or absence of bone marrow disease: (1) early after chemotherapy (between days 1 and 7) in patients without marrow infiltration, and (2) between days 9 and 16 in patients with marrow infiltration, ie, within the optimal time period for the collection of PBPCs. We show that there is a high proportion of patients with circulating tumor cells under steady-state conditions, and in addition a substantial risk of concomitant tumor cell recruitment upon mobilization of PBPCs, particularly in stage IV breast cancer patients with bone marrow infiltration. The biologic and clinical significance of this finding is unknown at present.


Cancer ◽  
2002 ◽  
Vol 94 (3) ◽  
pp. 707-712 ◽  
Author(s):  
Christian Marth ◽  
Jelena Kisic ◽  
Janne Kaern ◽  
Claes Tropé ◽  
Øystein Fodstad

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1818-1824 ◽  
Author(s):  
D Billadeau ◽  
L Quam ◽  
W Thomas ◽  
N Kay ◽  
P Greipp ◽  
...  

Abstract One of the distinguishing features of multiple myeloma (MM) is the proliferation of plasma cells that home to the bone marrow (BM). However, there still remains some uncertainty concerning the presence of related malignant cells in the peripheral blood of myeloma patients. Using consensus oligonucleotide primers, we amplified the third complementary determining region (CDR3) of rearranged immunoglobulin heavy chain alleles from MM marrow samples by polymerase chain reaction (PCR). From the sequences of the products, we derived allele-specific oligonucleotides (ASO), and these were used in subsequent amplification reactions to detect malignant clones in the peripheral blood of myeloma patients. This method is highly specific and sensitive to 1 malignant cell in the background of 10(5) normal cells. Using this method we detected circulating malignant cells in 13 of 14 previously untreated MM patients. Furthermore, by applying ASO-PCR to artificial titrations of initial BM DNA sample into normal peripheral blood lymphocyte (PBL) DNA we were able to generate standard curves and quantitate the amount of tumor in the patient PBL. We observed a wide variation in the amount of circulating tumor between patients. In addition, we found that the incidence of circulating tumor cells was independent of BM tumor burden and stage of disease. The detection and quantitation of circulating tumor cells in the PBL of MM patients may offer an alternative assessment of the disease and may be an important consideration in the use of peripheral stem cells in bone marrow transplantation.


2008 ◽  
Vol 15 (10) ◽  
pp. 2934-2942 ◽  
Author(s):  
Koshi Mimori ◽  
Takeo Fukagawa ◽  
Yoshimasa Kosaka ◽  
Kenji Ishikawa ◽  
Masaaki Iwatsuki ◽  
...  

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