Clinical application and pharmacokinetic study of nanocarriers in drug delivery system / 药学学报

Nanotechnology has shown obvious advantages in the field of medical treatment and diagnosis. Through the encapsulation of nano carriers, drugs not only enhance the therapeutic effect and reduce toxic and side effects, but also become intelligent responsive targeted drug systems through the modification on the surface of nano carriers. However, due to the obstacles in relevant basic research, production conditions, cost, clinical trials, and the lack of pharmacokinetic research on various drug loading systems, few nano systems have been used in therapy. In order to solve the above problems, this paper reviewed and analyzed the research progress of nano carriers in drug delivery, including their auxiliary role and characteristics, types and functions, pharmacokinetics, application prospects and challenges.

Predictive value of combination of MRI tumor regression grade and apparent diffusion coefficient for pathological complete remission after neoadjuvant treatment of locally advanced rectal cancer / 中华胃肠外科杂志

Objective: Pelvic high-resolution magnetic resonance imaging (MRI) has now become a standard method for evaluating the efficacy of neoadjuvant treatment for locally advanced rectal cancer (LARC). However, this traditional morphological qualitative assessment method based on T2-weighted imaging (T2WI) is not effective in predicting pathological complete remission (pCR). The purpose of this study is to investigate whether combining the magnetic resonance tumor regression grade (mrTRG) with apparent diffusion coefficient (ADC) can improve diagnostic value for pCR after preoperative neoadjuvant chemoradiotherapy (nCRT) of LARC. Methods: This was a diagnostic study. Clinicopathological data of 134 LARC patients who received nCRT and radical surgery in the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2019 were retrospectively analyzed. All the patients underwent MRI which included T2WI and DWI sequences before and 8 weeks after nCRT. Two radiologists independently drew ROIs on T2WI and DWI to estimate mrTRG stage and calculate the mean ADC value. Receiver operating characteristics (ROC) method was applied to evaluate the predict value of mrTRG combined with mean ADC value for pCR. Results: Of 134 LARC patients, 85 were male and 49 were female with median age of 58 (28-82) years. After nCRT, MRI suggested 21 patients (15.7%) had clinical complete remission (cCR), e.g. mrTRG stage 1-2. Postoperative pathology revealed 31 (23.1%) patients had pCR. The evaluations of mrTRG and ADC value by the two readers were highly consistent, and the intra-group correlation coefficients were 0.83 (95% CI: 0.703-0.881) and 0.96 (95% CI: 0.989-0.996), respectively. There was a negative correlation between mrTRG and pCR (r(s)=-0.505, P<0.01), and a positive correlation between mean ADC value and pCR (r(s)=0.693, P<0.01). The ROC curve showed that mrTRG alone had a medium predictive value for pCR, with an area under the curve (AUC) of 0.832 (95% CI: 0.743-0.921); the mean ADC value had a higher predictive value for pCR, with AUC of 0.906 (95% CI: 0.869-0.962). The predictive value of the combined model of mrTRG and ADC value for pCR was significantly better than that of mrTRG alone (P=0.015), and the AUC was 0.908 (95% CI: 0.849-0.968). Conclusion: Both mrTRG and mean ADC value can be non-invasive methods to predict the efficacy of nCRT for LARC. Combining the mean ADC value with mrTRG can result in better pCR prediction.

Construction of sRNA-deficient and-overexpressing strains of Yersinia pestis / 军事医学

Objective To construct small RNA deletion and overexpression strains with a length of less than 100 nt in Yersinia pestis.Methods Deletion mutants of the target sRNAs were constructed by increasing the length of homologous regions.Meanwhile, the high copy plasmid pBAD/HisA was modified into an inducible transcriptional vector as an sRNA-overexpression plasmid by using QuikChange lightning site-directed mutagenesis kit .The presence , size, and transcription-al initiation sites of the indicated sRNA were predicted by transcriptome sequencing , primer extension , and previous stud-ies.The full-length DNA fragments of target sRNAs were transformed into the transcriptional vector .The overexpressing strains of sRNAs were identified by Northern Blot .Results and Conclusion Four sRNAs deletion mutants of sR01, sR02, sR03 and HmsA and three sRNAs overexpression mutants MicF , HmsA and CpxQ were successfully constructed .A method of construction of sRNA deficient and overexpressing strains of Y.pestis has been quickly and efficiently established by λ-Red homologous recombination technology and QuikChange ? lightning site-directed mutagenesis kit.

Inhibitory effect of apatinib on HCT-116 cells and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of apatinib on colorectal carcinoma HCT-116 cells in vitro and the signaling pathways involved.</p><p><b>METHODS</b>The cytotoxicity of different concentrations (0, 0.5, 1, 1.5, and 2 µmol/L) of apatinib in HCT-116 cells was assessed by MTT assay, using capecitabine as the positive control. The apoptosis rate of apatinib-treated HCT-116 cells was detected using flow cytometry, and the expressions of Bcl-2, Bax, and caspase-3 were determined with quantitative real-time PCR and Western blotting. The effect of apatinib on the expressions of Akt, pAkt, Erk1/2 and pErk1/2 in HCT-116 cells was evaluated using Western blotting.</p><p><b>RESULTS</b>Apatinib significantly inhibited the proliferation of HCT-116 cells in a concentration-dependent manner with an ICvalue of 1.335 µmol/L. Flow cytometric analysis showed that apatinib significantly increased the apoptotic rate of HCT-116 cells dose-dependently. Apatinib induced the expression of the pro-apoptotic genes Bax and caspase-3 at both the mRNA and protein levels while inhibited the expression of the anti- apoptotic gene Bcl-2. The expressions of p-Akt and p-Erk1/2 were decreased in HCT-116 cells after apatinib treatment, but the total protein levels did not undergo obvious changes.</p><p><b>CONCLUSION</b>Apatinib inhibits the proliferation and induces apoptosis of HCT-116 cells by suppressing the phosphorylation of Erk1/2 and Akt in the MAPK/Erk and PI3K/Akt signaling pathways.</p>

Robo1 expression in non-small cell lung cancer and its brain metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of Robo1 in lung cancer tissues, adjacent non-cancerous tissues as well as lung cancer brain metastasis, and explore the correlation of Robo1 expression to lung cancer brain metastasis.</p><p><b>METHODS</b>SP (streptavidin-peroxidase) staining method was used to examine the Robo1 expression in specimens from 80 cases of NSCLC, 52 cases of adjacent non-cancerous tissues and 72 cases of lung cancer with single brain metastasis (without metastasis in other organs). The Robo1 expression was further examined in 17 self control cases with lung cancer tissues and their brain metastasis tissues. The results were assessed by Kaplan-Meier analysis and log-rank test.</p><p><b>RESULTS</b>The positive expression rate of Robo1 among adjacent non-cancerous tissues, lung cancers tissues and the lung cancer brain metastasis tissues were 1.9% (1/52), 13.8% (11/80) and 40.3% (29/72), respectively, and significant differences were detected among them (P < 0.05). During the 17 self control cases, the positive expression rate of Robo1 in lung cancer tissue and their brain metastasis tissues were 17.6% and 64.7%, respectively, with a significant difference between them (P < 0.01). Among the 72 cases of lung cancer brain metastasis, the median survival time of cases with positive Robo1 expression was 10 months, significantly shorter than that of cases with negative expression of Robo1 (17 months, P < 0.05).</p><p><b>CONCLUSIONS</b>The positive expression rate of Robo1 was increased in sequence from the lowest in adjacent non-cancerous tissues, intermediate in the lung cancer tissues to highest in the lung cancer brain metastasis tissues. The expression of Robo1 in lung cancer brain metastasis is negatively correlated with the prognosis of patients with lung cancer brain metastasis. Robo1 may promote the genesis and progression of lung cancer and lung cancer brain metastasis as a cancer-promoting oncogene.</p>

Expression of Notch1, MMP-2 and MMP-9 and their significance in glioma patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression of Notch1, MMP-2 and MMP-9 in glioma patients and their relationship with progression and prognosis of gliomas.</p><p><b>METHODS</b>Sixty-four cases of glioma were included in this study. There were four cases of grade 1 tumor, twenty-five cases of grade 2, nine cases of grade 3, and twenty-six cases of grade 4. Immunohistochemistry (SP staining method) was used to detect the expression of Notch1, MMP-2 and MMP-9 in glioma tissues and adjacent non-tumor tissues, and the patients were followed up.</p><p><b>RESULTS</b>Notch1, MMP-2 and MMP-9 were detected in glioma tissues but not in adjacent non-tumor tissues. The expression of Notch1 was increased with the pathological grade of the gliomas (r = 0.262, P < 0.05). The survival time of patients with strong expression of Notch1 was 31.0 months, significantly shorter than that of patients with non-strong positive (negative, weak and moderately) Notch1 expression (53.0 months, P < 0.05). Significant difference in survival time was observed between patients with negative and positive expression of MMP-9 (P < 0.05).</p><p><b>CONCLUSIONS</b>Notch1, MMP-2 and MMP-9 are closely correlated with the progression and prognosis of malignant gliomas. Notch1 may participate in the expression regulation of MMP-2 and MMP-9. Compared with MMP-2, MMP-9 may play a more important role in determining the prognosis of malignant glioma. Notch1 and MMP-9 may become new biological markers for prognosis of patients with malignant glioma.</p>

Effects of CDH1 gene promoter methylation on expression of E-cadherin and beta-catenin and its clinicopathological significance in colon carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship between methylation of the CDH1 gene promoter on the expression of E-cadherin and β-catenin, and to evaluate the correlation with clinicopathological characteristics of the colonic carcinoma.</p><p><b>METHODS</b>Methylation specific PCR (MSP) was used to detect CDH1 gene promoter methylation in the cancer tissue, adjacent tissues and normal tissues in 68 patients. The expression of E-cadherin and β-catenin was determined by immunohistochemistry staining.</p><p><b>RESULTS</b>The positive rate of CDH1 gene promoter methylation was 32.4% in adjacent tissues and 57.4% in cancer tissue, while no detectable methylation was found in all the normal tissues. The difference was statistically significant. The positive rate of E-cadherin was 92.6% in the normal tissues, 66.2% in the adjacent tissues and 44.1% in the cancer tissues. In all normal tissues, β-catenin was expressed only at the cellular membrane but not in the cytosol or nucleus, while the expression of β-catenin was present in the cytosol or nucleus in 29.4% of the adjacent tissues and 50.0% of the cancer tissues. The positive rate of CDH1 gene promoter methylation was negatively correlated with E-cadherin expression(r=-0.312, P=0.01) and positively correlated with β-catenin cytosolic/nucleus expression(r=0.309, P=0.018). The differentiation and metastasis of colonic carcinoma were associated with the aberrant expression of E-cadherin, β-catenin, and methylation of CDH1 promoter (P<0.05).</p><p><b>CONCLUSION</b>CDH1 gene promoter methylation may lead to aberrant expression of E-cadherin and β-catenin in colonic carcinoma, and may play an important role in promoting the invasion of tumor.</p>

Robo1 expression in breast cancer and its relationship to brain metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of Robo1 in different breast tumors and its association with the breast cancer brain metastasis.</p><p><b>METHODS</b>Labelled streptavidin-biotin (LSAB) staining was used to examine the Robo1 expression in specimens from 24 cases of invasive ductal carcinoma (IDC) with brain metastasis, 71 cases of IDC without brain metastasis, 22 cases of ductal carcinoma in situ (DCIS) and 23 cases of fibroadenoma.</p><p><b>RESULTS</b>The expression pattern of Robo1 in DCIS (59.1%) and IDC (45.3%) was significantly lower than that in adenofibroma (87.0%, P < 0.05). The expression of Robo1 in IDC with brain metastasis (12.5%) was significantly lower than that in IDC without brain metastasis (56.3%, P < 0.05). The expression of Robo1 was much higher in more than 50 year-old-group (57.8%) than that in less than 50 year-old-group (34.0%) of IDC patients. The overall survival time in patients with the Robo1 negative expression was significantly shorter than those with positive expression (P < 0.05). No correlation was found between the Robo1 expression and the tumor size, lymph node metastasis, pathologic stage, histological grade and clinical stage (P > 0.05).</p><p><b>CONCLUSIONS</b>The Robo1 expression correlates negatively with IDC brain metastasis, and correlates positively with the age and prognosis of IDC patients. Robo1 may be applied as a marker in evaluation of the IDC prognosis and brain metastasis.</p>

Predictive value of (99)Tc(m)-MIBI scintimammography in evaluation of the efficacy of neoadjuvant chemotherapy in patients with operable breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the value of technetium-99m methoxyisobutylisonitrile ((99)Tc(m)-MIBI) imaging in predicting the efficacy of neoadjuvant chemotherapy (NCT) and prognosis in patients with operable breast cancer.</p><p><b>METHODS</b>Sixty five patients with breast cancer underwent (99)Tc(m)-MIBI scintimammography before NCT, and static planar images were taken at 10 min and 180 min after scintimammography. The clearance rate was calculated in each patient, correlation between the clearance rate and efficacy of NCT, and the disease free survival rate were analyzed.</p><p><b>RESULTS</b>The mean clearance rate of 65 patients was (17.4 ± 6.8)%. The efficacy of NCT was 86.2% (CR 4 cases, PR 52 cases, SD 8 cases, and PD 1 case), and the mean clearance rate of patients with good response or poor response of chemotherapy were (15.5 ± 5.0)% and (29.2 ± 3.2)%, respectively. There was a significant difference between the two groups. The average disease free survival rate in the group with low clearance rate was (75.8%, P = 0.046), significantly higher than that in the group with high clearance rate (53.1%).</p><p><b>CONCLUSION</b>Scintimammography of (99)Tc(m)-MIBI may be used to evaluate the efficacy and prognosis of NCT for patients with operable breast cancer.</p>

The relationship between 99mTc-MIBI scintimammography of breast cancer and multidrug-resistant proteins / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between the clearance rate of technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) in scintimammography and multidrug-resistant proteins expression in breast cancer tissues.</p><p><b>METHODS</b>Seventy-six patients with breast cancer underwent (99m)Tc-MIBI scintimammography before treatment, and static planar images were taken at 10 min and 180 min after scintimammography. The clearance rate of (99m)Tc-MIBI was calculated in each patient. Immunohistochemical analysis was performed on pathological specimens of the 76 breast tumors to determine the expression of P-glycoprotein (P-gp), glutathione S-transferase Pi (GST-pi) and topoisomerase II (Topo II).</p><p><b>RESULTS</b>The clearance rate was significantly higher in 36 patients with positive P-gp expression when compared with that in 40 patients with negative P-gp expression. There was no significant relationship between GST-pi, Topo II and the clearance rate of (99m)Tc-MIBI.</p><p><b>CONCLUSION</b>The clearance rate of (99m)Tc-MIBI in breast imaging may be used to evaluate the P-gp level in breast cancers.</p>

Growth inhibition of human hepatocellular carcinoma xenograft in nude mice by combined treatment with human cytokine-induced killer cells and chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the inhibitory effects of cytokine-induced killer (CIK) cells alone, chemotherapeutic drug alone, and CIK cells combined with chemotherapeutic drug on the growth of hepatocellular carcinoma (HCC) cells transplanted in nude mice.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMC) collected from five healthy donors by blood cell separator were incubated in vitro to induce CIK cells in the presence of interferon-gamma (IFN-gamma), IL-2 and anti-CD3 monoclonal antibody (mAb). The phenotype of CIK cells was characterized by flow cytometric analysis. BEL-7402 HCC cells were inoculated subcutaneously to nude mice. On day 5, at the inoculation site were injected normal saline (group 1), CIK cells (3 x 10(7) and 6 x 10(7), group 2 and 3), mitomycin-C (MMC 80 microg in 0.2 ml, group 4), and CIK cells combined with MMC (group 5), respectively.</p><p><b>RESULTS</b>The percentage of CD3(+), CD3(+)CD8(+), CD3(+)CD56(+), CD25(+) cells increased from 64.0%, 28.0%, 7.8%, and 9.1% to 94.7%, 67.7%, 61.3%, and 84.0% respectively after cytokine induction. The percentage of CD3(+) and CD3(+)CD8(+) cells remained at high levels during incubation period, but that of CD25(+) and CD3(+)CD56(+) cells peaked respectively on day 7 and 13 and then declined. During the 90-day observation, the tumor formation rates were 100%, 70.0%, 80.0%, 70.0% and 66.7%; and the mouse survival rates were 10.0%, 60.0%, 40.0%, 50.0% and 75.0%, respectively from group 1 to group 5. Compared to the other groups, in the combined therapy group of mice, not only the tumor grew slowly and but also showed more marked tissue necrosis.</p><p><b>CONCLUSION</b>The growth inhibitory effect on human HCC transplanted in nude mice of combined CIK cells and MMC treatment is more potent than that of CIK cells or MMC alone.</p>