Clear cell renal cell carcinoma with cystic component similar to multilocular cystic renal neoplasm of low malignant potential: a rare pattern of cyst-dependent progression from multilocular cystic renal neoplasm of low malignant potential.

BACKGROUND: For clear cell renal cell carcinoma (ccRCC) with cystic component similar to multilocular cystic renal neoplasm of low malignant potential (MCRN-LMP) and solid low-grade component simultaneously, we propose the designation "ccRCC with cystic component similar to MCRN-LMP" and to study the relationship between MCRN-LMP and it. METHODS: Twelve cases of MCRN-LMP and 33 cases of ccRCC with cystic component similar to MCRN-LMP were collected from 3,265 consecutive RCCs to compare them in clinicopathological features, immunohistochemical findings (PAX8, CA-IX, CK7, Vimentin, CD10, P504s, TFE3, 34ßE12) and prognosis. RESULTS: There was no significant difference in age, sex ratio, tumor size, treatment, grade and stage between them (P > 0.05). All ccRCCs with cystic component similar to MCRN-LMP coexisted with MCRN-LMP and solid low-grade ccRCCs, and MCRN-LMP component ranged from 20 to 90% (median, 59%). The positive ratio of CK7 and 34ßE12 in MCRN-LMPs and ccRCCs' cystic parts was significantly higher than that in ccRCCs' solid parts, but the positive ratio of CD10 in MCRN-LMPs and ccRCCs' cystic parts was significantly lower than that in ccRCCs' solid parts (P < 0.05). There was no significant difference of all immunohistochemistry profiles between MCRN-LMPs and ccRCCs' cystic parts (P > 0.05). No patient developed recurrence or metastasis. CONCLUSIONS: MCRN-LMP and ccRCC with cystic component similar to MCRN-LMP have similarity and homology in clinicopathological features, immunohistochemical findings and prognosis, and form a low-grade spectrum with indolent or low malignant potential behavior. The ccRCC with cystic component similar to MCRN-LMP may be a rare pattern of cyst-dependent progression from MCRN-LMP.

Expression of nucleophosmin/NPM1 correlates with migration and invasiveness of colon cancer cells.

BACKGROUND: We aimed to examine the expression level of Nucleophosmin (NPM1) protein in colon cancer tissues and to investigate the potential role of NPM1 in the regulation of cell migration and invasiveness. METHODS: Immunohistochemical assay was performed to examine the expression pattern of NPM1 in 31 groups of colonic carcinoma samples, including colon tumors, adjacent normal tissues, and matched metastatic lymph nodes from the same patients. Small interfering RNA technique and exogenous expression of wild type NPM1 methods were used to further verify the function of NPM1. RESULTS: High-expression of NPM1 correlates with lymph node metastasis (P = 0.0003) and poor survival rate of human colon cancer patients (P = 0.017). SiRNA-mediated reduction of NPM1 was also shown to inhibit the migration and invasiveness of metastatic colon cancer HCT116 cell line. In addition, the exogenous expression of NPM1 in HT29 cells, a NPM1 low expression and low invasive colon cancer cell line, enhanced cell migration and invasiveness along with increased cell proliferation. CONCLUSIONS: The current study uncovered the critical role of NPM1 in the regulation of colon cancer cells migration and invasion, and NPM1 may serve as a potential marker for the prognosis of colon cancer patients.

Pathologic responses to neoadjuvant chemoimmunotherapy in primary limited-stage small-cell lung cancer.

BACKGROUND: Immunotherapy has been proved to have a large effect on extensive-stage small cell lung cancer, but the role of immunotherapy in limited-stage small-cell lung cancer (LS-SCLC) is still unknown. METHODS: A retrospective study of six patients with LS-SCLC who were treated with neoadjuvant chemoimmunotherapy (durvalumab plus etoposide combined with cisplatin) was performed. Patients were evaluated by the safety, feasibility and pathologic responses of neoadjuvant chemoimmunotherapy. RESULTS: Neoadjuvant durvalumab combined chemotherapy was associated with few immediate adverse events and did not delay planned surgery. All patients achieved partial pathologic response (pPR) instead of major pathologic response, or pathologic complete response. No association was observed between programmed death-ligand 1 expression in tumor specimens and the pathologic response. However, tumors with high expression of immune cells such as CD4+ T cells, CD8+ T cells and FoxP3+ Tregs tended to have better pathologic responses than tumors with low expression of immune cells. CONCLUSIONS: Neoadjuvant durvalumab combined chemotherapy could induce pPR with few side effects in resectable LS-SCLC. The immune cells in the tumor microenvironment might play an important role in neoadjuvant chemoimmunotherapy in resectable LS-SCLC.

Same knot, longer rope: altering ligand geometry provides control over nuclearity in self-assembled trefoil knots.

Taking advantage of the accumulation of a number of noncovalent intramolecular interactions, octanuclear and hexanuclear trefoil knots are self-assembled based on half-sandwich rhodium fragments. The selective synthesis of either the octanuclear or hexanuclear knot can be controlled by altering different dipyridyl arms.

[Differential proteomics in glioblastoma].

OBJECTIVE: To establish differential proteomics profiles of glioblastoma cell lines from Chinese, and to provide reference for future basic studies. METHODS: Total protein was extracted from 3 glioblastoma cell lines, CHG-5, TJ899 and TJ905. After normalization, the total protein was presented by two-dimensional (2D) electrophoresis, scanned and analyzed. Some of the identified protein spots were verified by immunocytochemistry of cell lines and immunohistochemistry of solid tumors. The glia cells were used as the control throughout the study. RESULTS: A total of 13 differential protein spots were selected, and eventually 10 were identified as unique proteins. These 10 proteins were involved in cytoskeleton forming, cellular metabolism, tumor migration, stress and inflammatory reaction. Immunocytochemistry and immunohistochemistry further confirmed these proteins present in the solid tumors. CONCLUSION: Distinct differential proteomics profiles exist in glioblastoma cell lines and normal glia cells, likely related to the transformation of normal glia to glioma.

[Effects of endostatin and doxycycline on microcirculation patterns in melanoma and their relevant molecular mechanisms].

OBJECTIVE: To investigate the effects of endostatin and doxycycline on microcirculation patterns in melanoma and their molecular mechanisms. METHODS: To establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell suspension. The mice were divided into 3 experimental groups and 1 control group. To treat the mice in the 3 experimental groups with endostatin, doxycycline, endostatin and doxycycline, respectively, and the control group without any treatment. The tumor volume was measured and recorded to make comparison of their growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemical staining. The three microcirculation patterns of endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The activity of MMP-2, MMP-9 between different groups was examined by gelatin zymography. RESULTS: Tumor growth in the three experimental groups was statistically significantly slower than that in the control group. The expression of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with that in the control group. The amount of three microcirculation patterns in three experimental groups was less than that of the control group, and the amount of MV and VM in each experimental group was significantly less than that in the control group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP-2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control group, but the enzyme activity of pro-MMP-2 among the four groups was not significantly different. CONCLUSION: The combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.

[Study on the molecular mechanism of endostatin and doxycycline in suppressing melanoma growth].

OBJECTIVE: To investigate the molecular mechanism of endostatin and doxycycline effect on melanoma growth. METHODS: A B16 melanoma mice model was established by intracutaneous injection of B16 cell suspension. The mice were treated with endostatin, doxycycline, endostatin and doxycycline respectively, the control group received no treatment. A time course study of tumor volume was performed to observe the antitumor effect. The expression of matrix metalloproteinase (MMP-9), MMP-2, TIMP-2 were examined by immunohistochemistry staining. RESULTS: Tumors in endostatin treatment group, doxycycline treatment group, endostatin and doxycycline treatment group grew slower than in the control group. The difference of the average tumor volume in the doxycycline group and control group, in the doxycycline with endostatin treatment group and control group were statistically different. The positive expression ratio of MMP-2, MMP-9, TIMP-2 in each treatment group were statistically different from their control groups (F = 12.79, F = 5.56, F = 4.64; P < 0.05). CONCLUSION: Doxycycline and endostatin are able to inhibit the expression of MMPs and promote expression of TIMP, which ultimately inhibits the growth of B16 melonoma.

Potential mechanisms of benzyl isothiocyanate suppression of invasion and angiogenesis by the U87MG human glioma cell line.

Glioma is one of the most common tumors in China and chemotherapy is critical for its treatment. Recent studies showed that benzyl isothiocyanate (BITC) could inhibit the growth of glioma cells, but the mechanisms are not fully understood. This study explored the inhibitory effect of BITC on invasion and angiogenesis of U87MG human glioma cells in vitro and in vivo, as well as potential mechanisms. It was found that BITC could inhibit invasion and angiogenesis of human glioma U87MG cells by inducing cell cycle arrest at phase G2/M. It also was demonstrated that BITC decreased expression of cyclin B1, p21, MMP-2/9, VE-cadherin, CD44, CXCR4 and MTH1, the activity of the telomerase and PKCζ pathway. Microarray analysis was thus useful to explore the potential target genes related to tumorigenic processes. BITC may play important roles in the inhibition of invasion and angiogenesis of human glioma cells.