Influence of Serum TGF-β1 and EGFR Levels on the Therapeutic Effect of High-Dose AraC in Patients with Acute Myeloid Leukemia Based on the Decision Curve / 中国实验血液学杂志

OBJECTIVE@#To analyze the influence of serum levels of transforming growth factor-β1 (TGF-β1) and epidermal growth factor receptor (EGFR) on the therapeutic effect of high-dose cytarabine (HD-AraC) in patients with acute myeloid leukemia (AML).@*METHODS@#98 patients with AML treated in our hospital from January 2019 to June 2020 were selected as the research subjects, all patients were treated with HD-AraC for 1 course of treatment every week. The effect of 2 groups were evaluated during after one course of treatment and divided into effective group and ineffective group, statistical table of baseline data was designed, the baseline data of 2 groups were counted in detail, the baseline data and serum levels of TGF-β1 and EGFR of 2 groups were compared, Logistic regression analysis was used to examine the relationship between the levels of serum TGF-β1, EGFR and the therapeutic effect of HD-AraC in patients with AML, the value of serum TGF-β1 and EGFR levels in predicting the therapeutic effect of HD-AraC in AML patients was analyzed based on ROC curve and decision curve.@*RESULTS@#After 1 course of treatment, among the 98 patients, 26 cases had complete remission, 38 cases had partially remission and 34 cases no remission, the total effective rate was 65.31% (64/98); after comparing data of 2 groups, Logistic regression analysis showed that the overexpression of serum EGFR before treatment might be a risk factor for the ineffective treatment of HD-AraC in AML patients (OR>1, P<0.05), overexpression of serum TGF-β1 before treatment might be a protective factor for the ineffective treatment of HD-AraC in AML patients (OR<1, P<0.05); the ROC curve results showed that the AUC of serum EGFR and TGF-β1 before treatment in predicting the risk of ineffective HD-AraC treatment in AML patients were >0.70, which had certain predictive value. The decision curve results showed that in the threshold range of 0.15-044, the prediction model combined with serum EGFR and TGF-β1 levels in predicting the net benefit rate of HD-AraC treatment in AML patients was better than that of serum EGFR or serum TGF-β1 alone.@*CONCLUSION@#The levels of serum TGF-β1 and EGFR affect the therapeutic effect of HD-AraC in patients with AML and increase the risk of ineffective treatment, serum TGF-β1 and EGFR can be used to predict the risk of ineffective HD-AraC treatment in AML patients, and the combined prediction of net benefit rate is higher.

A prospective study assessing feasibility of performing percutaneous nephrolithotomy in chronic kidney disease patients - What factors affect the outcome?

ABSTRACT Objectives To primarily evaluate the functional outcomes of PCNL for bilateral renal calculi/calculi in solitary functioning kidney with Chronic Kidney Disease(CKD). To identify factors affecting the renal replacement therapy following PCNL. Materials and Methods Patients with bilateral renal calculi/calculi in solitary kidney and CKD (eGFR<60/s.creatinine>2) and Good Performance Status [Eastern Cooperative Oncology Group (ECOG): 0-2] were included in the study. Results A total of 60 patients with CKD who had bilateral renal calculi/calculi in solitary functioning kidney underwent PCNL. At 6 months, eGFR improved or stabilized in 45 (75%) patients, while in 15 (25%) patients eGFR deteriorated. A total of 5 (14.28%) and 2 (25%) patients of CKD stage 4 and 5 respectively had improvement in eGFR as well as CKD stage. Fourteen (82.35%), 21 (60%), 3 (37.5%) patients of CKD stage 3, 4, 5 had improvement in eGFR but not significant enough to cause stage migration. Again 3 (17.65%) , 9 ( 40%) and 3 (37.5%) patients of CKD stage 3, 4, 5 had reduction in eGFR but not significant enough to cause stage migration. None of the patients had worsening of CKD stage. Preoperative CKD stage and eGFR were compared with measurements made at the final follow up visit (6 months). Conclusion Our results indicate that most patients of renal calculi with CKD show improvement or stabilization of renal function with aggressive stone removal. Improvement is more in patients who have mild to moderate CKD. Aggressive management of comorbidities, peri-operative UTI and complications may delay or avoid progression of CKD status in such patients.

Detection of circulating tumor cells by nested RT-PCR targeting EGFR/CEA/CK20mRNAs in colorectal carcinoma patients

EGFR is involved in the epidermal growth factors pathway that regulates cellular processes and is associated with the development of many types of cancer including colorectal cancer. Molecular methods with high sensitivity such as nested polymerase chain reaction [PCR] based assays have been used to search for tumor cell specific markers. This study aimed to detect the circulating EGFRmRNA expressing tumor cells and its diagnostic value in colorectal cancer compared with that of known markers of circulating cancer cells CEA and CK20. This study included 36 patients diagnosed as having colon cancer of different stages and 18 matched healthy controls. The staging was carried out according to the TNM classification. We used nested RT-PCR-based reverse transcription PCR assay for the detection of circulating cancer cells in the peripheral blood. The blood samples from the colon cancer patients showed detection of EGFR in 15/36 patients [41.7%]; CEAmRNA in 22/36 patients [61.1%] and CK20mRNA in 24/36 patients [66.7%]. No evidence of EGFR mRNA expression in any of the samples used as controls. 3/18 [16.7%] and 4/18 [22.2%] of healthy controls gave a positive result of CEA/CK20mRNAs. There was a statistically significant difference in the prevalence of EGFR/CEA and CK20mRNAs expression between the early disease group [stage I and II] and the advanced disease group [stage III and IV] [P < 0.01]. Colon cancer patients with a high level of serum CEA exhibited detectable concentrations of EGFR and CEA and CK20mRNAs more often than those with a low serum CEA level, there is significant difference [P < 0.01]. EGFR assay might represent a suitable marker for detection of circulating tumor cells in colon cancer patients. CEA and CK20mRNAs are significantly more frequently detected in colon cancer patients than in healthy controls supports the hypothesis that they are promising complementary markers for CRC diagnosis. The assessment of multiple molecular tumor markers improved the sensitivity in detecting circulating tumor cells but due to limited specificity; identification and validation of genes and proteins implicated in metastatic processes need to be further investigated

Prognostic value of epidermal growth factor receptor and P27 protein expression in colorectal carcinoma

Clinicopathological data and the expression of direct cellular growth, epidermal growth factor receptor [EGFR] and tumor suppressor gene p27 were studied by immunohistochemistry on paraffin-embedded sections of 50 cases of primary colorectal carcinoma [CRC] in Egyptian patients, to evaluate their role in predicting patients prognosis. EGFR was expressed in 26 out of 50 cases [52%]. There is a significant conrrelation between expression of EGFR and tumor differentiation [p < 0.001] and 5-year survival rate [p < 0.001]. EGFR expression had no statistically significant correlation with Clinicopathological parameters including histological type, size, site, and stage. Lack or low p27 expression was noted in 15 out of 50 [30%] cases of CRC [p < 0.05]. This altered expression was significantly higher in proximal cancer [p < 0.05], mucinous tumors [p < 0.001], poorly differentiated histololgy [p < 0.01]. Overall survival was better in the patient group with altered level of p27 expression, although the difference does not reach statistical significance [p > 0.05]. In conclusion, EGFR overexpression has been found to be related to a poor prognosis of CRC, and loss or p27 protein expression was associated with poorly differentiated CRC and may be part of the genetic pathway, which is responsible for the development of some CRC

Non small cell lung cancer molecular biomarkers in blood

Several studies have reported significant correlations between individual telomerase activity and apoptosis in malignant tumours including lung cancer. Such studies were carried out on tissue biopsies from the malignant tissue. The aim of the present study was to determine molecular biological parameters that can he used for early biological predisposition for lung cancer. Telomerase activity and Bcl-2 anti-apoptotic protein in circulating lymphocytes, plasma nitric oxide. epidermal growth factor and epidermal growth 'actor receptor were measured in the blood of 25 non small cell lung cancer [NSCLC] patients amid in 20 normal age and socio-economic matching controls, Results revealed significant increase in telomerase activity [53 +/- 8.2 vs. 19.5 +/- 4.8. p<0.0001] between cancer patients and normal controls, significant lower levels of Bcl-2 [7 2 +/- 1,5 vs. 10.4 +/- 1.4 micro g/ml, t 7.3. p<0.0000001] among cancer patients compared to normal controls, However, there were significantly higher levels of epidermal growth factors [6.2 +/- 2 05 vs 0.2 +/- 0.01 pg/ml], epidermal growth factor receptor EGFR [134 +/- 4.7 vs. 102 +/- 2.2 fmol/ml] and plasma nitrate/nitrite [18.8 +/- 4.7 vs. 12.5 +/- 5 micro g/ml. 1=-5.25. p<0.0001] in lung cancer patients compared to controls. This study reveals that Bcl-2 levels in circulating peripheral blood are weak biomarkers for lung cancer, while increase in plasma telomerase activity, NO and EGF levels can he used as reliable biomarkers for cancer prognosis

Diagnostic value of CD34, epidermal growth factor receptor [EGFR] expression and proliferation in vesicular mole and persistent gestational trophoblastic disease

Identifying patients with increased risk for developing persistent trophoblastic disease [PTD] following evacuation of hydatiform mole, whether partial or complete, is essential to prevent unnecessary prophylactic chemotherapy. It is challenging to find an adequate diagnostic modality that identifies patients at increased risk for developing PTD. This study was investigating villous angiogenesis by identification of CD34 antigen, trophopastic epidermal growth factor receptor [EGFr] as well as trophoblastic cell proliferation to predict the risky patients with molar pregnancy. Thirty aborted patients were conducted for clinical examination, ultrasonography, and estimation of serum human chorionic gonadotropin [HCG] before abortion and frequent measurement after evacuation for six months. Contents of evacuation were fixed in buffered formalin [10%], processed, paraffin embedded and 4 sets of sections were subjected for hematoxylin and eosin stain, immunohistochemistry using monoclonal CD34 and EGFr antibodies and silver stain to asses proliferative potentiality by counting the Argerophilic nucleolar organizer regions [AgNor]. Clinical, ultrasonographic examination revealed molar pregnancy in 25 cases. Histopathologic examination of post evacuation tissue revealed normal pattern of chorionic villi in 5 cases and they were considered as control. Patterns consistent with partial vesicular mole [PVM] were detected in 12 case and features of complete vesicular mole [CVM] were seen in 13 cases. Persistent elevation of HCG-alpha titer after evacuation was detected in 4 molar cases [16%] [one out of 12 partial mole cases [8.33%] and 3 of the 13 complete partial moles [23.08%]. Immunohistochemistry study comprised frequent expression of CD34 with increased microvessel density per villous [MVD/villous] in control cases [mean 7.5 +/- 0.56]. The microvessels located at the periphery beneath vasculosyncytial membrane to perform margination. However, the mean MVD/Villous was significantly reduced in PVM and CVM [3 +/- 0.75 and 1.75 +/- 0.68 respectively]. In 5 out of 12 PVM [41.7%] the micro vessels were located centrally while rest cases perform margination. Contrary, in all CVM specimens the micro vessels if present were located centrally. In control group, EGFr The trophoblasts were negative for EGFr expression, while in PVM group, trophoblasts displayed mild to moderate expression in 5/12 [41.67%] with a mean of 1.8 +/- 0.58. Contrary, all CVM showed moderate to strong expression of EGFr [mean=2.56 +/- 0.75]. High expression of EGFr was in parallel with decreased MVD/villous. There was increased EGFr expression in 3 cases that were associated with persistent elevation of serum HCG following evacuation [1/12 [8.3%] was PVM and 2/13 [15.4%] were CVM]. Proliferative potential was noticed to be increased with increased AgNor count in the trophblasts of CVM versus PVM and control groups [4.29 +/- 1.25, 1.98 +/- 0.32 and 1.1 +/- 0.07 respectively]. Significant reduction of MVD/Villous and increased expression of EGFr confirm diagnosis h of CVM. In addition, absence of CD34 positive micro vessels and high expression of EGFr could be used as markers to predict the possibility for persistent trophoblastic disease, providing better chance for early medical intervention

Expression of epidermal growth factor receptor-1 in chronic schistosomal urinary bladder lesions

Over expression of growth factors including epidermal growth factor receptor [EGFR], have been implicated in bladder cancer biology. This study was conducted in a trial to a better understanding the genetic mechanisms underlying the proliferative, the premalignant and malignant changes frequently displayed in chronic schistosomal cystitis [ChSC] and schitosoma associated carcinoma of the bladder. The study included 58 Egyptian patients [15 ChSC and 43 bladder cancer], and 5 normal urothelial specimens as control. The bladder cancer specimens were selected included adjacent normal mucosa or dysplastic areas [27 squamous cell carcinoma SCC and 16 transitional cell carcinoma TCC]. Level of expression of EGFR was analyzed using an immunohistochemical approach and the results compared with histological pattern, grading and pathological staging. In normal epithelium EGFR expression was only limited to the basal layer, but in dysplastic epithelium adjacent to tumour tissue all cells stained for EGFR. Bilharzial associated TCC exhibit very low expression, EGFR expression was weak cytoplasmic or even absent. The majority of SCC expressed strong membrane staining for EGFR and almost all cells were positive for the receptor. However, the intensity of staining was increasing with a significant statistical correlation with grade [p < 0.01] and with invasiveness of the tumour [p < 0.001]. In conclusion over expression of EGFR [high intensity] in human bladder cancer may be associated with poor differentiation and with invasion that could be implicated in the pathway of oncogenesis for schitosoma associated SCC of the bladder