• Journal of Pharmaceutical Investigation
• /
• v.36 no.5
• /
• pp.309-314
• /
• 2006

The multicellular layers(MCL) of human cancer cells is a three dimensional(3D) in vitro model for human solid tumors which has been used primarily for the assessment of avascular penetration of anti-cancer drugs. For anti-cancer drugs with penetration problem, MCL represents a good experimental model that can provide clinically relevant data. Calcein-AM is a fluorescent dye that demonstrates the cellular vitality in a graded manner in cancer cell culture system. In the present study, we evaluated the use of calcein-AM for determination of anti-proliferative activity of anti-cancer agents in MCL model of DLD-1 human colorectal cancer cells. Optical sectioning of confocal imaging was compromised with photonic attenuation and penetration barrier in the deep layers of MCL. By contrast, fluorescent measurement on the cryo-sections provided a feasible alternative. Cold pre-incubation did not enhance the calcein-AM distribution to a significant degree in MCL of DLD-1 cells. However, the simultaneous determination of drug penetration and cellular vitality appeared to be possible in drug treated MCL. In conclusion, these data suggest that calcein-AM can be used for the simultaneous determination of drug-induced anti-proliferative effect and drug penetration in MCL model.

• Journal of Microbiology and Biotechnology
• /
• v.34 no.3
• /
• pp.506-515
• /
• 2024

Primary human dermal papilla cells (HDPCs) are often preferred in studies on hair growth and regeneration. However, primary HDPCs are limited by their reduced proliferative capacity, decreased hair induction potential, and extended doubling times at higher passages. To overcome these limitations, pTARGET vectors containing human papillomavirus16 (HPV16) E6/E7 oncogenes were transfected into HDPCs and selected using G-148 to generate immortalized cells here. HPV16 E6/E7 oncogenes were efficiently transfected into primary HDPCs. Immortalized HDPC showed higher proliferative activity than primary HDPC, confirming an increased proliferation rate. Expression of p53 and pRb proteins was downregulated by E6 and E7, respectively. E6/E7 expressing HDPC cells revealed that cyclin-dependent kinase (CDK) inhibitor p21 expression was decreased, while cell cycle-related genes and proteins (CDK2 and cyclin E) and E2F family genes were upregulated. Immortalized HDPCs maintained their responsiveness to Wnt/β-catenin pathway and hair follicle formation capability, as indicated by their aggregative properties and stemness. E6/E7 immortalized HDPCs may facilitate in vitro hair growth and regeneration studies.

• IMMUNE NETWORK
• /
• v.4 no.2
• /
• pp.88-93
• /
• 2004

Background: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigenpresenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. Methods: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. Results: MSC inhibit the CD83 and HLA-class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-$\gamma$ production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. Conclusion: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2001.10a
• /
• pp.148-148
• /
• 2001

Genistein, a phytoestrogen derived from soy isoflavone, has been shown to exert anti-proliferative activities, and have cell arrest and apoptotic effects in cultured tumor cells. However, these properties may not show at the low concentrations of genistein. Present study examined the effect of different concentrations of genistein on cell proliferative proteins, cell cycle regulators or apoptosis related protein in comparison with different concentrations of estrogen or co-treatment with estrogen.(omitted)

• Journal of Acupuncture Research
• /
• v.23 no.2
• /
• pp.21-31
• /
• 2006

In the present study, We have investigated the bee venom (BV) and melittin (a major component of BV)-mediated anti-proliferative effects, and defined its mechanisms of action in cultured rat aortic vascular smooth muscle cells (VSMCs). BV and melittin $(0.4{\sim}0.8\;{\mu}g/ml)$ effectively inhibited 5% FBS-induced VSMCs proliferations. The regulation of apoptosis has attracted much attention as a possible means of eliminating excessively proliferating VSMCs. In the present study, the treatment of BV and melittin strongly induced apoptosis of VSMCs. These results suggest that the anti-proliferative effects of BV and melittin in VSMCs should be related with induction of apoptosis. Further study about Influence of BV and melittin upon apoptosis mechanism is therefor thought to be necessary to confirm the above results.

• BMB Reports
• /
• v.47 no.12
• /
• pp.660-665
• /
• 2014

Stathmin 1 is a microtubule destabilizer that plays an important role in cell cycle progression, segregation of chromosomes, clonogenicity, cell motility and survival. Stathmin 1 overexpression has been reported in malignant hematopoietic cells and Stathmin 1 inhibition reduces the highly proliferative potential of leukemia cell lines. However, during the differentiation of primary hematopoietic cells, Stathmin 1 expression decreases in parallel to decreases in the proliferative potential of early hematopoietic progenitors. The scope of the present review is to survey the current knowledge and highlight future perspectives for Stathmin 1 in normal and malignant hematopoiesis, with regard to the expression, function and clinical implications of this protein.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.256.1-256.1
• /
• 2002

We investigated the anti-proliferative effects of a new compound. ircinin-1. from the sponge Sarcotragus sp. on SK-MEL -2 human skin cancer cells. From the data of MTT assay, cell viability was decreased by ircinin-1 in a dose-dependent manner. We observed that the anti-proliferative effect of ircinin-1 was due to the induction of apoptosis, which was confirmed by observing the morphological changes. the increased ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2, and cleavage of poly(ADP-ribose) polymerase protein, via activation of caspase-3. (omitted)

• The Korean Journal of Cytopathology
• /
• v.4 no.1
• /
• pp.52-56
• /
• 1993

Proliferative fasciitis is a benign pseudosarcomatous mesenchymal lesion occurring in the subcutis. The lesion occurs clinically as a tumorous mass that develops within a rather short time in elderly patients. We recently experiecened a case of fine needle aspiration cytology of proliferative fasciitis in the left anterior chest wall of a 72 year-old male patient. The smear revealed two types of cells. One was the large and mostly oval cell with one or two nuclei lying at the periphery of the cell body and abundant basophilic cytoplasm like the ganglion cell. The nuclei were round to oval, had vesicular chromatin and contained prominent nucleoli. The other was the spindle shaped fibroblast with an oval nucleus. The differential diagnosis includes a true tumor such as ganglioneuroma, rhabdomyosarcoma, and liposarcoma and therefore fine needle aspiration cytology is very much indicated in order to exclude these possibilities.

• Journal of Life Science
• /
• v.26 no.12
• /
• pp.1392-1399
• /
• 2016

Jaspine B is an anhydrophytosphingosine that is isolated from a marine sponge. Because of its structural similarity to sphingosine, it shows anti-cancer effects in human carcinomas. Therefore, this study aims to investigate its anti-proliferative effect on various cancer cells and to correlate its association with the intracellular accumulation of Jaspine B in relevant cancer cells. The anti-proliferative effect of Jaspine B in various cancer cells was determined by a cell viability test, and the intracellular concentration of Jaspine B in relevant cancer cells was determined using mass spectrometry coupled with liquid chromatography. The correlation coefficient and p value between the cytotoxicity and the cell accumulation of Jaspine B were determined using SPSS 16.1. The cytotoxicity of Jaspine B varied depending on the type of cancer cell when compared the $EC_{50}$ values of Jaspine B. Breast and melanoma cancer cells were susceptible to Jaspine B, whereas renal carcinoma cells were resistant. The intracellular concentrations of Jaspine B had a reciprocal correlation with the $EC_{50}$ values in the same cells (r = 0.838). The results suggested that the anti-proliferative effect of Jaspine B was associated with the cellular accumulation of this compound. However, Jaspine B was not a substrate for P-glycoprotein and breast cancer resistance protein, as major efflux pumps caused multidrug resistance. The maintenance of a high intracellular concentration is crucial for the cytotoxic effect of Jaspine B; however, efflux pumps may not be a controlling factor for Jaspine B-related resistance in cancer cells.

• Korean Journal of Veterinary Research
• /
• v.33 no.4
• /
• pp.597-603
• /
• 1993

The purpose of this stady was to investigate division cells by in vivo bromodeoxyuridine(Brdur) immunohistochemistry for labeling the proliferative epithelial cells in the gastrointestinal tracts of rats. Rats were administrated intraperitonially by twice consecutive injections of 24 hr interval with Brdur(0.05mg/g BW/time) and then were sacrificied at 1 hour after last injection. The specimens were taken from the stomach, small intestine(ileum), and large intestine(colon). The well-oriented crypts and villi in the preparations were examined, The crypt columns and villi were devided into 10 segments from crypt base to surface of the lumen or to villis top. Labeling index(LI) was measured by counting the number of Brdur-positive cells against the total number of crypt column cells in the stomach and large intestine and also against the total numbers of crypt column and it's villi epiterial cells in the small intestine. 1. In the stomach, the LI in each part from segment 1 to segment 10 of the crypt column were 4.2%, 5.0%. 6.6%, 9.0%, 11.3%, 15.3%, 9.3%, 15.6%, 11.3%, 0%, respectively and it's mean LI were 8.7%. The Brdur-positive epithelial cells were predominantly located in the middle regions and middle-upper regions of the crypt columns. 2. In the small intestine, the LI in each part from segment 1 to segment 10 of were 62.4%, 50.9%, 27.8%, 22.5%, 18.6%, 12.1%, 7.5%, 4.3%, 2.5%, 1.4%, respectively and it's mean LI were 21.0%. The Brdur-positive epithelial cells were predominantly located in the lower regions of the crypt columns and tended to be less in the higher regions of the villi than that in the crypt column. 3. In the large intestine, the LI in each part from segment 1 to segment 10 of the crypt column were 19.4%, 29.9%, 34.1%, 41.6%, 41.2%, 32.4%, 25.4%, 15.4%, 10.8%, 1.2%, respectively and it's mean LI were 25.1%, The Brdur-positive epithelial cells were predominantly in the middle and middle-lower regions of the crypt columns. 4. The organs with higher LI were ordered as the large intestine(25.1%), small intestine(21.0%) and stomach(8.7%).