Evaluation of Human Platelet Lysate as an Alternative to Fetal Bovine Serum for Potential Clinical Applications of Stem Cells from Human Exfoliated Deciduous Teeth.

In recent years, there has been a surge in demand for and research focus on cell therapy, driven by the tissue-regenerative and disease-treating potentials of stem cells. Among the candidates, dental pulp stem cells (DPSCs) or human exfoliated deciduous teeth (SHED) have garnered significant attention due to their easy accessibility (non-invasive), multi-lineage differentiation capability (especially neurogenesis), and low immunogenicity. Utilizing these stem cells for clinical purposes requires careful culture techniques such as excluding animal-derived supplements. Human platelet lysate (hPL) has emerged as a safer alternative to fetal bovine serum (FBS) for cell culture. In our study, we assessed the impact of hPL as a growth factor supplement for culture medium, also conducting a characterization of SHED cultured in hPL-supplemented medium (hPL-SHED). The results showed that hPL has effects in enhancing cell proliferation and migration and increasing cell survivability in oxidative stress conditions induced by H2O2. The morphology of hPL-SHED exhibited reduced size and elongation, with a differentiation capacity comparable to or even exceeding that of SHED cultured in a medium supplemented with fetal bovine serum (FBS-SHED). Moreover, no evidence of chromosome abnormalities or tumor formation was detected. In conclusion, hPL-SHED emerges as a promising candidate for cell therapy, exhibiting considerable potential for clinical investigation.

Growth inhibition by fusidic acid in cervical, thyroid, and breast carcinoma cell lines.

OBJECTIVE: We investigated the effects of fusidic acid (FA) on human cervical, thyroid, and breast carcinoma cell lines to determine the potential usefulness of FA in cancer treatment. METHODS: Six cancer cell lines (cervical cancer: Caski, HeLa; thyroid cancer: 8505C, TPC1; and breast cancer: MCF-7, MDA-MB-231) were treated with FA. Furthermore the changes in cell growth, cell cycle duration, and extent of apoptosis were analyzed. RESULTS: After FA treatment, the cancer cells showed a decrease in growth rate. In the cell death assay, the cell populations were similar in each cell type after treatment with FA, indicating that growth inhibition by FA was not related to the induction of apoptosis. FA induced cell cycle arrest at a dose that inhibited growth rate, which varied in different cell types. G0/G1 phase arrest occurs in breast cancer, S phase arrest in 8505C thyroid cancer, and G2/M phase arrest in cervical cancer. These results indicate that FA reduces growth rates by inducing cell cycle arrest. CONCLUSION: FA treatment can interfere with cell proliferation by inducing cell cycle arrest in human cervical, thyroid, and breast carcinoma cell lines. Thus, FA can be useful in treating human cervical, thyroid, and breast carcinomas.

The Potential Application of Human Gingival Fibroblast-Conditioned Media in Pulp Regeneration: An In Vitro Study.

Regenerative endodontic treatment based on tissue engineering has recently gained interest in contemporary restorative dentistry. However, low survival rates and poor potential differentiation of stem cells could undermine the success rate of pulp regenerative therapy. Human gingival fibroblast-conditioned medium (hGF-CM) has been considered a potential therapy for tissue regeneration due to its stability in maintaining multiple factors essential for tissue regeneration compared to live cell transplantation. This study aimed to investigate the potency of hGF-CM on stem cells from human dental pulp (DPSC) in pulp regeneration. A series of experiments confirmed that hGF-CM contributes to a significant increase in proliferation, migration capability, and cell viability of DPSC after H2O2 exposure. Moreover, it has been proved to facilitate the odontogenic differentiation of DPSC via qRT-PCR, ALP (alkaline phosphatase), and ARS (Alizarin Red S) staining. It has been discovered that such highly upregulated odontogenesis is related to certain types of ECM proteins (collagen and laminin) from hGF-CM via proteomics. In addition, it is found that the ERK pathway is a key mechanism via inhibition assay based on RNA-seq result. These findings demonstrate that hGF-CM could be beneficial biomolecules for pulp regeneration.

Photonic Microbeads Templated by Oil-in-Oil Emulsion Droplets for High Saturation of Structural Colors.

Photonic microbeads containing crystalline colloidal arrays are promising as a key component of structural-color inks for various applications including printings, paintings, and cosmetics. However, structural colors from microbeads usually have low color saturation and the production of the beads requires delicate and time-consuming protocols. Herein, elastic photonic microbeads are designed with enhanced color saturation through facile photocuring of oil-in-oil emulsion droplets. Dispersions of highly-concentrated silica particles in elastomer precursors are microfluidically emulsified into immiscible oil to produce monodisperse droplets. The silica particles spontaneously form crystalline arrays in the entire volume of the droplets due to interparticle repulsion which is unperturbed by the diffusion of the surrounding oil whereas weakened for oil-in-water droplets. The crystalline arrays are permanently stabilized by photopolymerization of the precursor, forming elastic photonic microbeads. The microbeads are transferred into the refractive-index-matched biocompatible oil. The high crystallinity of colloidal arrays increases the reflectivity at stopband and the index matching reduces incoherent scattering at the surface of the microbeads, enhancing color saturation. The colors can be adjusted by mixing two distinctly colored microbeads. Also, low stiffness and high elasticity reduce foreign-body sensation and enhance fluidity, potentially serving as pragmatic structural colorants for photonic inks.

Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.

The response rate to treatment with trastuzumab (Tz), a recombinant humanized anti-HER2 monoclonal antibody, is only 12-34% despite demonstrated effectiveness on improving the survival of patients with HER2-positive breast cancers. Selenium has an antitumor effect against cancer cells and can play a cytoprotective role on normal cells. This study investigated the effect of selenium on HER2-positive breast cancer cells and the mechanism in relation to the response of the cells to Tz. HER2-positive breast cancer cell lines, SK-BR-3 as trastuzumab-sensitive cells, and JIMT-1 as Tz-resistant cells were treated with Tz and sodium selenite (selenite). Cell survival rates and expression of Her2, Akt, and autophagy-related proteins, including LC3B and beclin 1, in both cell lines 72 h after treatment were evaluated. Significant cell death was induced at different concentrations of selenite in both cell lines. A combined effect of selenite and Tz at 72 h was similar to or significantly greater than each drug alone. The expression of phosphorylated Akt (p-Akt) was decreased in JIMT-1 after combination treatment compared to that after only Tz treatment, while p-Akt expression was increased in SK-BR-3. The expression of beclin1 increased particularly in JIMT-1 after only Tz treatment and was downregulated by combination treatment. These results showed that combination of Tz and selenite had an antitumor effect in Tz-resistant breast cancer cells through downregulation of phosphorylated Akt and beclin1-related autophagy. Selenite might be a potent drug to treat Tz-resistant breast cancer by several mechanisms.

Bacterial extracellular vesicles affect endocrine therapy in MCF7 cells.

BACKGROUND: : The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy. METHODS: : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK. CONCLUSION: : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.

Selective inhibition of V600E-mutant BRAF gene induces apoptosis in thyroid carcinoma cell lines.

PURPOSE: Papillary thyroid cancer (PTC) has a high incidence of BRAFV600E mutation. The purpose of this study was to evaluate the potential relationship between thyroiditis and BRAFV600E mutation status in patients with PTC. We investigated how a selective inhibitor of BRAFV600E PLX4032 affects the proliferation and inflammatory cytokine levels of thyroid cancer. METHODS: Two thyroid cancer cell lines TPC1 and 8505C were treated with PLX4032, an analysis was done on cell growth, cell cycle, the degree of apoptosis, and levels of inflammatory cytokines. To identify the functional links of BRAF, we used the STRING database. RESULTS: Docking results illustrated PLX4032 blocked the kinase activity by exclusively binding on the serine/threonine kinase domain. STRING results indicated BRAF is functionally linked to mitogen-activated protein kinase. Both cell lines showed a dose-dependent reduction in growth rate but had a different half maximal inhibitory concentration value for PLX4032. The reaction to PLX4032 was more sensitive in the 8505C cells than in the TPC1 cells. PLX4032 induced a G2/M phase arrest in the TPC1 cells and G0/G1 in the 8505C cells. PLX4032 induced apoptosis only in the 8505C cells. With PLX4032, the TPC1 cells showed decreased levels of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, chemokine (C-C motif) ligand 2/monocyte chemoattractant protein 1, whereas the 8505C cells showed significantly decreased levels of IL-8, serpin E1/plasminogen activator inhibitor-1, and matrix metalloproteinase (MMP)-3. CONCLUSION: PLX4032 was cytotoxic in both TPC1 and 8505C cells and induced apoptosis. In the 8505C cells, inflammatory cytokines such as IL-8 and MMP-3 were down-regulated. These findings suggest the possibility that the BRAFV600E mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer.

Sodium Selenite Enhanced the Anti-proliferative Effect of MEK-ERK Inhibitor in Thyroid Cancer Cells.

BACKGROUND/AIM: MEK-ERK pathway plays major roles in the progression of thyroid cancer, while the use of MEK-ERK inhibitors has been limited by its toxicity. We investigated the effect of sodium selenite as an adjunct for MEK-ERK inhibitors to avoid the toxicity of ERK inhibitors. MATERIALS AND METHODS: TPC1, 8505C and HTori-3 cells were treated with U0126 (MEK-ERK inhibitor) and cell viability was counted in the Neubauer chamber. The synergistic effects of sodium selenite and U0126 were also measured. The expression of ERK, p-ERK, and p90RSK was determined by western blot. RESULTS: Treatment with U0126 inhibited proliferation of TPC1 and 8505C cells in a dose-dependent manner. When 5 µM sodium selenite was added to 1 µM U0126, relative cell survival further decreased. Decreased expression of p90RSK indicated that sodium selenite down-regulated ERK signaling in thyroid cancer cells. CONCLUSION: The combination of U0126 and sodium selenite inhibited proliferation of thyroid cancer cells through ERK inhibition.

Circulating Plasmacytoid and Myeloid Dendritic Cells in Breast Cancer Patients: A Pilot Study.

PURPOSE: Dendritic cells (DC) are a class of bone marrow-derived cells found in the blood, epithelia, and lymphoid tissues, and are the most efficient antigen presenting cells. The number and function of DC can change dramatically in cancer patients. The aim of this study is to correlate the levels of circulating DC subsets with clinical characteristics in breast cancer patients. METHODS: Peripheral blood samples were collected from 53 untreated breast cancer patients before surgery between January 2013 and November 2013. Forty-one healthy, age-matched volunteers served as the control group. The phenotypes of circulating plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were determined using fluorescence activated cell sorting assays. Correlations between DCs immunophenotypes and clinicopathologic characteristics of these breast cancer patients were then determined. RESULTS: Patients with breast cancer had higher levels of pDCs (p = 0.046). No relationships were observed with tumor stage and intrinsic subtype. Estrogen receptor (ER) positive patients had higher levels of mDCs than ER negative patients (p = 0.025) and human epidermal growth factor receptor 2 (HER-2) positive patients had higher levels of pDCs than HER-2 (p = 0.040). No relationships were observed with T stage, N stage, Ki67 index, histologic grade, nuclear grade, and lymphovascular invasion. In multiple regression analysis, patients with HER-2 positive breast cancer had higher levels of pDCs than HER-2 negative patients (p = 0.026). CONCLUSION: An increase of pDCs in the peripheral blood of breast cancer patients was observed and patients with HER-2 positive breast cancer had higher levels of circulating pDCs than did HER-2 negative patients. Our results suggest that expression of DCs can differ according to breast cancer subtype and indicate that, with further investigation, DC expression has the possibility of being presented as a prognostic factor.

Is augmentation with the long head of the biceps tendon helpful in arthroscopic treatment of irreparable rotator cuff tears?

BACKGROUND: Although various surgical techniques have been used to treat irreparable rotator cuff tears (RCTs), debate remains regarding which treatment is most effective. The purpose of our study was to compare the outcomes of partial rotator cuff repair versus repair with augmentation of the tenotomized long head of the biceps tendon (LHBT). METHODS: This study included 76 patients with large to massive RCTs. Arthroscopic rotator cuff repair with LHBT augmentation was performed in 39 patients (group I), while partial repair was performed in 37 patients (group II). Clinical and functional outcomes were compared with a visual analog scale for pain and the American Shoulder and Elbow Surgeons score, Constant score, and Korean Shoulder Score. Magnetic resonance imaging was performed 12 months after surgery. RESULTS: The mean follow-up period was 29.6 ± 7.8 months (range, 24-51 months). Significant improvements in pain and clinical scores were observed in both groups at the last follow-up. However, there were no significant differences in pain, clinical scores, or range of motion between the 2 groups at any time point. Retears were observed in 16 patients in group I (41.0%) and 14 in group II (37.8%, P = .78). Augmented LHBT pathology was observed in 10 patients (25.6%). CONCLUSIONS: Both partial repair and repair with LHBT augmentation were effective in improving clinical and radiologic outcomes. No significant differences in clinical outcomes or repaired cuff integrity were observed between the groups. The investment of operation time and effort in augmenting the LHBT in the treatment of irreparable RCTs is not recommended.

Transforming growth factor-ß decreases side population cells in hepatocellular carcinoma in vitro.

Hepatocellular carcinoma (HCC) can result from hepatitis B or C infection, fibrosis or cirrhosis. Transforming growth factor-ß (TGF-ß) is one of the main growth factors associated with fibrosis or cirrhosis progression in the liver, but its role is controversial in hepatocarcinogenesis. In the present study, the effect of TGF-ß on the HCC Huh-7 and Huh-Bat cell lines was evaluated. To study the effect of TGF-ß, Huh-7 and Huh-Bat cells were treated with TGF-ß and a TGF-ß receptor inhibitor (SB431542). Cell survival, cell cycle, numbers of side population (SP) cells and expression of the cancer stem cell marker cluster of differentiation (CD)133, epithelial-mesenchymal transition markers (E-cadherin, α-smooth muscle actin and vimentin) and TGF-ß-regulated proteins [phospho-c-Jun N-terminal kinase (p-JNK), p-c-Jun and p-smad2] were investigated. TGF-ß treatment resulted in decreased cell survival with a targeted effect on SP cells. Expression of CD133 and vimentin was upregulated by treatment with the TGF-ß receptor antagonist SB431542, but not with TGF-ß. By contrast, TGF-ß induced accumulation of cells at G0/G1, and upregulated expression of p-JNK, p-c-Jun and p-smad2. However, these effects were blocked when cells were treated with TGF-ß plus SB431542, indicating the specificity of the TGF-ß effect. The present results indicated that TGF-ß has anticancer effects mediated by survival inhibition of cancer stem cells, which may be developed as a novel therapy for HCC.

Minimally Invasive Lateral Lumbar Interbody Fusion for Adult Spinal Deformity: Clinical and Radiological Efficacy With Minimum Two Years Follow-up.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To evaluate the clinical and radiological efficacies of supplementing minimally invasive lateral lumbar interbody fusion (LLIF) with open posterior spinal fusion (PSF) in adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: Minimally invasive techniques have been increasingly applied for surgery of ASD. Few reports have been published that directly compare LLIF combined with PSF to conventional PSF for ASD. METHODS: To evaluate the advantages of minimally invasive LLIF for ASD, patients who underwent minimally invasive LLIF followed by open PSF (combined group) were compared with patients who only underwent PSF (only PSF group). The clinical and radiological outcomes for deformity correction and indirect decompression were assessed. The occurrence of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) were also evaluated. RESULTS: No significant differences were observed in the clinical outcomes of the Oswestry Disability Index (ODI), visual analog scale, and major complications including reoperations between the groups. No additional advantage was found for coronal deformity correction, but the restoration of lumbar lordosis in the combined group was significantly higher postoperatively (15.3° vs. 8.87°, P = 0.003) and last follow-up (6.69° vs. 1.02°, P = 0.029) compared to that of the only PSF group. In the subgroup analysis for indirect decompression for the combined group, a significant increase of canal area (104 vs. 122 mm) and foraminal height (16.2 vs. 18.5 mm) was noted. The occurrence of PJK or PJF was significantly higher in the combined group than in the only PSF group (P = 0.039). CONCLUSION: LLIF has advantages of indirect decompression and greater improvements of sagittal correction compared to only posterior surgery. LLIF should be conducted considering the above-mentioned benefits and complications including PJK or PJF in ASD. LEVEL OF EVIDENCE: 4.

Dexamethasone reduces side population fraction through downregulation of ABCG2 transporter in MCF-7 breast cancer cells.

Side population (SP) cells represent a rare population among breast cancer cells. SP cells have been reported to act as cancer stem­like cells, and to participate in the development of multidrug resistance via modulating the expression of ATP-binding cassette subfamily G member 2 (ABCG2). Dexamethasone is a corticosteroid drug that has been used as an adjuvant treatment to enhance the efficacy of chemotherapeutic agents; however, its effects in breast cancer have yet to be thoroughly investigated. In the present study, the effects of dexamethasone were investigated using the human MCF­7 breast cancer cell line, and SPs were examined in detail. Cellular proliferation, SP fractions and ABCG2 expression were examined following treatment of MCF­7 cells with dexamethasone. Dexamethasone was revealed to cause a dose­ and time­dependent decrease in cancer cell proliferation, and it also decreased the size of the SP fraction of MCF­7 cells and the expression of the ABCG2 transporter. The effects of dexamethasone on cellular proliferation, SP fraction and ABCG2 expression were abolished following the administration of the glucocorticoid antagonist RU486. These results suggested that dexamethasone may target breast cancer cell SPs and thus increase the sensitivity of tumor cells to chemotherapy. Therefore, it may be hypothesized that dexamethasone can be used as a chemosensitizer in the adjuvant treatment of patients with breast cancer.

3-bromopyruvate and buthionine sulfoximine effectively kill anoikis-resistant hepatocellular carcinoma cells.

BACKGROUND & AIMS: Acquisition of anoikis resistance is a prerequisite for metastasis in hepatocellular carcinoma (HCC). However, little is known about how energy metabolism and antioxidant systems are altered in anoikis-resistant (AR) HCC cells. We evaluated anti-tumor effects of a combination treatment of 3-bromopyruvate (3-BP) and buthionine sulfoximine (BSO) in AR HCC cells. METHODS: We compared glycolysis, reactive oxygen species (ROS) production, and chemoresistance among Huh-BAT, HepG2 HCC cells, and the corresponding AR cells. Expression of hexokinase II, gamma-glutamylcysteine synthetase (rGCS), and epithelial-mesenchymal transition (EMT) markers in AR cells was assessed. Anti-tumor effects of a combination treatment of 3-BP and BSO were evaluated in AR cells and an HCC xenograft mouse model. RESULTS: AR HCC cells showed significantly higher chemoresistance, glycolysis and lower ROS production than attached cells. Expression of hexokinase II, rGCS, and EMT markers was higher in AR HCC cells than attached cells. A combination treatment of 3-BP/BSO effectively suppressed proliferation of AR HCC cells through apoptosis by blocking glycolysis and enhancing ROS levels. In xenograft mouse models, tumor growth derived from AR HCC cells was significantly suppressed in the group treated with 3-BP/BSO compared to the group treated with 3-BP or sorafenib. CONCLUSIONS: These results demonstrated that a combination treatment of 3-BP/BSO had a synergistic anti-tumor effect in an AR HCC model. This strategy may be an effective adjuvant therapy for patients with sorafenib-resistant HCC.

Trichuris trichiura Infection in North Korean Defector Resulted in Chronic Abdominal Pain and Growth Retardation.

Trichuris trichiura infection is a common helminth infection, which is transmitted via soil, with worldwide distribution, especially in rural areas of developing countries. Occasionally, sporadic cases occur in non-endemic, developed areas due to the widespread of immigration. We experienced a case of Trichuris dysentery syndrome in a young North Korean defector, who had been suffering from chronic abdominal pain for 10 years. He is relatively short and thin compared with his older brother. Unexpectedly, the diagnosis, made by a colonoscopy, revealed numerous, small, white, and gently moving worms at the cecum and ascending colon. After 3 days of albendazole (400 mg once daily) administration, clinical symptoms subsided dramatically. On the follow-up colonoscopy, which was performed two months after the completion of his treatment, complete eradication was identified. Soil-transmitted helminths, including Trichuris trichiura, are disappearing becoming less prevalent in South Korea as a result of both national driving force and environmental improvement. However, these diseases should be considered when we meet foreign patients from developing countries, like North Korea, presenting chronic abdominal pain. Moreover, proper treatment of North Korean defectors and performing cohort studies of them would help to prepare for the possible unification era in the field of gastroenterology.

Radiation hazards to vascular surgeon and scrub nurse in mobile fluoroscopy equipped hybrid vascular room.

PURPOSE: The aim of the present study was to identify the radiation hazards to vascular surgeons and scrub nurses working in mobile fluoroscopy equipped hybrid vascular operation rooms; additionally, to estimate cumulative cancer risk due to certain exposure dosages. METHODS: The study was conducted prospectively in 71 patients (53 men and 18 women) who had undergone vascular intervention at our hybrid vascular theater for 6 months. OEC 9900 fluoroscopy was used as mobile C-arm. Exposure dose (ED) was measured by attaching optically stimulated luminescence at in and outside of the radiation protectors. To measure X-ray scatter with the anthropomorphic phantom model, the dose was measured at 3 distances (20, 50, 100 cm) and 3 angles (horizontal, upward 45°, downward 45°) using a personal gamma radiation dosimeter, Ecotest CARD DKG-21, for 1, 3, 5, 10 minutes. RESULTS: Lifetime attributable risk of cancer was estimated using the approach of the Biological Effects of Ionizing Radiation report VII. The 6-month ED of vascular surgeons and scrub nurses were 3.85, 1.31 mSv, respectively. The attenuation rate of lead apron, neck protector and goggle were 74.6%, 60.6%, and 70.1%, respectively. All cancer incidences among surgeons and scrub nurses correspond to 2,355 and 795 per 100,000 persons. The 10-minute dose at 100-cm distance was 0.004 mSv at horizontal, 0.009 mSv at downward 45°, 0.003 mSv at upward 45°. CONCLUSION: Although yearly radiation hazards for vascular surgeons and scrub nurses are still within safety guidelines, protection principles can never be too stringent when aiming to minimize the cumulative harmful effects.

17ß-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling.

17ß-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC.

The effect of Lactobacillus casei extract on cervical cancer cell lines.

AIM OF THE STUDY: Lactobacillus casei (L. casei) has been shown to inhibit the proliferation of several types of cancer in vivo, but its effect on cervical cells has not been reported. We incubated cells of the human cervical cell lines Caski and HeLa with extracts of L. casei and investigated its effects on the growth of the cells and possible synergy with anticancer drugs. MATERIAL AND METHODS: Cell-free extracts of L. casei were prepared and purified. Cultures of Caski and HeLa cells adhering to tissue culture plates were treated with L. casei extract. The effects of L. casei extract on the growth of cancer cells and its possible synergy with anti-cancer drugs in cervical cancer cell lines were investigated. The cells were treated with L. casei extract alone, anti-cancer drugs alone [doxorubicin, paclitaxel, 5-fluorouracil (5-FU), and cisplatin], or L. casei extract plus anti-cancer drugs. RESULTS: L. casei extract had no significant effect on the growth rate of the two cell lines. Anti-cancer drugs alone induced growth inhibition, but there was no synergistic effect of L. casei extract on growth inhibition. CONCLUSIONS: L. casei extract does not have a potent effect on the viability of cervical cancer cells in vitro. In addition, L. casei extract has no synergistic effect on the inhibition of growth of cancer cells in the presence of anti-cancer drugs.

Sorafenib inhibits cancer side population cells by targeting c­Jun N­terminal kinase signaling.

Sorafenib is a systemic chemotherapeutic agent for advanced hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the anticancer effect of sorafenib in cancer stem cell­like cells, such as side population (SP) cells, in HCC and to analyze the signaling pathway for drug­resistance. To evaluate the anticancer effects of sorafenib, Huh7 and Huh­BAT cells were treated with sorafenib, fluorouracil (5­FU), and sorafenib plus 5­FU. These cells were examined for growth rates, the SP fraction, sphere­forming efficacy and expression of c­Jun N­terminal kinase (JNK) signaling molecules. Sorafenib and 5­FU treatment decreased growth rates in Huh7 and Huh­BAT cells; however, the treatments exerted different effects in SP cells and on the expression levels of JNK signaling molecules. Treatment with 5­FU increased the SP cell number and upregulated the expression of JNK signaling molecules. By contrast, sorafenib decreased the SP cell number and downregulated the expression of JNK signaling molecules. No significant differences in sphere­forming efficacy were observed subsequent to 5­FU and sorafenib treatment in Huh7 and Huh­BAT cells. These results indicate that sorafenib exerted anticancer effects in HCC and SP cells by targeting JNK signaling.