• Archives of Plastic Surgery
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• v.35 no.6
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• pp.637-644
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• 2008

Purpose: The survival of bone marrow derived stem cell was reported several times. But the survival of adipose tissue derived stem cells(hASCs) was not mentioned on. We studied the adipose tissue derived stem cell's survival and effect on articular cartilage in rabbits. Methods: Osteoarthritis was induced in twenty New Zealand white rabbits by intraarticular injection of monosodium iodoacetate(MIA). After four weeks, hASCs were also injected into the knee joints space without any vehicle, but the control group received phosphate buffered saline only. The histologic grade of articular cartilage was measured in 4 and 8 weeks after the transplantation of hASC and the viability of injected stem cells measured by Fluorescent in situ Hybridization (FISH) examination. Results: After 4 and 8 weeks from hASCs transplantation, histologic grade was not significantly difference between two groups(p>0.05), and the Y chromosome of the transplanted hASCs was not detected in articular cartilage. Conclusion: We found that direct injection of hASC in joint space didn't work on damaged articular cartilage repair.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.43 no.3
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• pp.166-170
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• 2017

Objectives: To define the risk of occult cervical metastasis of maxillary squamous cell carcinoma (SCC) and the therapeutic value of elective neck dissection (END) in survival of clinically negative neck node (cN0) patients. Materials and Methods: Sixty-seven patients with maxillary SCC and cN0 neck were analyzed retrospectively, including 35 patients with maxillary gingiva and 32 patients with maxillary sinus. Results: Of 67 patients, 10 patients (14.9%) had occult cervical metastasis. The incidence of occult cervical metastasis of maxillary gingival SCC was higher than that of maxillary sinus SCC (17.1% and 12.5%, respectively). The 5-year overall survival rate was 51.9% for the END group and 74.0% for the non-END group. The success rate of treatment for regional recurrence was high at 71.4%, whereas that for local or locoregional recurrence was low (33.3% and 0%, respectively). Conclusion: The incidence of occult cervical metastasis of maxillary SCC was not high enough to recommend END. For survival of cN0 patients, local control of the primary tumor is more important than modality of neck management. Observation of cN0 neck is recommended when early detection of regional recurrence is possible irrespective of the site or T stage. The key enabler of early detection is patient education with periodic follow-up.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.315-320
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• 2013

Background: TGF-${\beta}$-activated kinase-1 (TAK1) has been found to be over-expressed in a variety of solid malignancies and related to tumor growth. The aim of this study was to evaluate the expression level of TAK1 in clear cell renal cell carcinoma (ccRCC) and assess its value as a novel prognostic marker. Methods: TAK1 mRNA was assessed in 51 paired ccRCC tissues and adjacent normal tissues (ADTs) by real-time PCR. Tissue TAK1 protein was also assessed in 91 ADTs and 177 samples of ccRCC immunohistochemically for evaluation of relationships with clinical characteristics. Results: RT-PCR showed that TAK1 RNA level was significantly higher in ccRCC tissues than in the paired ADTs and immunohistochemistry confirmed higher expression of TAK1 protein in ccRCC samples compared with ADTs. TAK1 protein expression in 177 ccRCC samples was significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, but not age and gender. Patients with low TAK1 levels had a better survival outcome. TAK1 expression and N stage were independent prognosis factors for the overall survival of ccRCC patients. Conclusions: Overexpression of TAK1 predicts a poor prognosis in patients with ccRCC, so that TAK1 may serve as a novel prognostic marker.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.991-996
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• 2015

Side population (SP) cells have stem cell-like properties with a capacity for self-renewal and are resistant to chemotherapy and radiotherapy. Therefore the presence of SP cells in human breast cancer probably has prognostic value. Objective: To investigate the characteristics of SP cells and identify the relationship between the SP cells levels and clinico-pathological parameters of the breast tumor and disease-free survival (DFS) in breast cancer patients. Materials and Methods: A total of 122 eligible breast cancer patients were consecutively recruited from January 1, 2006 to December 31, 2007 at Yunnan Tumor Hospital. All eligible subjects received conventional treatment and were followed up for seven years. Predictors of recurrence and/or metastasis and DFS were analyzed using Cox regression analysis. Human breast cancer cells were also obtained from fresh human breast cancer tissue and cultured by the nucleic acid dye Hoechst33342 with Verapami. Flow cytometry (FCM) was employed to isolate the cells of SP and non-SP types. Results: In this study, SP cells were identified using flow cytometric analysis with Hoechst 33342 dye efflux. Adjusted for age, tumor size, lymph nodal status, histological grade, the Cox model showed a higher risk of recurrence and/or metastasis positively associated with the SP cell level (1.75, 1.02-2.98), as well as with axillary lymph node metastasis (2.99, 1.76-5.09), pathology invasiveness type (1.7, 1.14-2.55), and tumor volume doubling time (TVDT) (1.54, 1.01-2.36). Conclusions: The SP cell level is independently associated with tumor progression and clinical outcome after controlling for other pathological factors. The axillary lymph node status, TVDT and the status of non-invasive or invasive tumor independently predict the prognosis of breast cancer.

• Radiation Oncology Journal
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• v.37 no.2
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• pp.73-81
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• 2019

Purpose: There is sparse literature on treatment outcomes research on resectable oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to measure the treatment outcomes, explore the failure patterns, and identify the potential clinicopathological prognostic factors affecting treatment outcomes for resectable OTSCC. Materials and Methods: It is a retrospective analysis of 202 patients with resectable OTSCC who underwent upfront primary surgical resection followed by adjuvant radiotherapy with or without concurrent chemotherapy if indicated. Results: The median follow-up was 35.2 months (range, 1.2 to 99.9 months). The median duration of locoregional control (LRC) was 84.9 months (95% confidence interval, 67.3-102.4). The 3- and 5-year LRC rate was 68.5% and 58.3%, respectively. Multivariate analysis showed that increasing pT stage, increasing pN stage, and the presence of extracapsular extension (ECE) were significantly associated with poorer LRC. The median duration of overall survival (OS) was not reached at the time of analysis. The 3- and 5-year OS rate was 70.5% and 66.6%, respectively. Multivariate analysis showed that increasing pT stage and the presence of ECE were significantly associated with a poorer OS. Conclusion: Locoregional failure remains the main cause of treatment failure in resectable OTSCC. There is scope to further improve prognosis considering modest LRC and OS. Pathological T-stage, N-stage, and ECE are strong prognostic factors. Further research is required to confirm whether adjuvant therapy adds to treatment outcomes in cases with lymphovascular invasion, perineural invasion, and depth of invasion, and help clinicians tailoring adjuvant therapy.

• Parasites, Hosts and Diseases
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• v.55 no.5
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• pp.505-512
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• 2017

Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant ${\alpha}-GalCer$. As results, TgCPC1 DNA vaccine with or without adjuvant ${\alpha}-GalCer$ showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and $IFN-{\gamma}$ in the spleen compared to controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). Upon challenge infection with tachyzoites of T. gondii (RH), $pCPC1/{\alpha}-GalCer$ immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.

• Archives of Reconstructive Microsurgery
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• v.18 no.1
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• pp.9-15
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• 2009

Whether a seven days course of anti-${\alpha}{\beta}$-T cell receptor-antibody (${\alpha}{\beta}$-TCRmAb) combined with FK506 therapy promotes survival of limb allografts in fully MHC-mismatched combination (Brown Norway $\rightarrow$ Lewis) was examined. Eight animals received 250 ${\mu}g$/kg/day of ${\alpha}{\beta}$-TCRmAb for 7 days and 2 mg/kg/day of FK506 postoperatively (Combination therapy group). Eight animals had FK506 only (Mono-therapy group) and five animals did not have treatment (Control group). Clinical signs of early rejection with edema or erythema in the skin occurred at an average of 8.6${\pm}$1.5 days postoperatively in Control group and 59.0${\pm}$8.3 days in Mono-therapy group, both of which proceeded to irreversible rejection with necrosis of the epidermis and finally mummification. In Combination therapy group, all animals showed evidence of early rejection at an average of 56.8${\pm}$12.6 days postoperatively, however, in 4 of 8 limbs, early rejection resolved without any treatment and limbs survived >1 year. At 9 months postoperatively, donor skin grafts were accepted and third-party skin grafts were rejected by all four survivors, demonstrating donor-specific tolerance. Little or no detectable chimerism was observed in any of the 4 surviving animals at one-year postoperatively. Combination therapy of ${\alpha}{\beta}$-TCRmAb and FK506 resulted in long-term survival in fully MHC-mismatched limb transplants.

• Parasites, Hosts and Diseases
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• v.56 no.4
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• pp.325-334
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• 2018

Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicate a need for the development of an effective vaccine. T. gondii GRA8 is a member of the dense granules protein family and is used as a marker of acute infection. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent GFP-RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii of this vaccine were analyzed by measuring cytokine and serum antibody titers, splenocyte proliferation assays, and the survival times of mice after challenge. Our results showed that mice immunized with pDsRed2-GRA8 demonstrated specific humoral and cellular responses, induced higher IgG antibody titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70), $IFN-{\gamma}$, $TNF-{\alpha}$, and splenocyte proliferation; and prolonged survival times compared to those of control mice. The present study showed that DNA immunization with pDsRed2-GRA8 induced humoral and cellular immune responses, and all immunized mice showed greater Th1-type immune responses and longer survival times than those of control mice. These results indicated that T. gondii GRA8 DNA immunization induces a partial protective effect against acute toxoplasmosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6581-6589
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• 2015

Background: Previously, stingless bee (Trigona spp.) products from East Kalimantan, Indonesia, were successfully screened for in vitro antiproliferative activity against human cancer derived cell lines. It was established that propolis from T. incisa presented the highest in vitro cytotoxicity against the SW620 colon cancer cell line (6% cell survival in $20{\mu}g/mL$). Materials and Methods: Propolis from T. incisa was extracted with methanol and further partitioned with n-hexane, ethyl acetate and methanol. The in vitro cytotoxicity of the extracts was assessed by the MTT assay against human colon (SW620), liver (Hep-G2), gastric (KATO-III), lung (Chago) and breast (BT474) cancer derived cell lines. The active fractions were further enriched by silica gel quick column, absorption and size exclusion chromatography. The purity of each fraction was checked by thin layer chromatography. Cytotoxicity in BT-474 cells induced by cardanol compared to doxorubicin were evaluated by MTT assay, induction of cell cycle arrest and cell death by flow cytometric analysis of propidium iodide and annexin-V stained cells. Results: A cardol isomer was found to be the major compound in one active fraction (F45) of T. incisa propolis, with a cytotoxicity against the SW620 ($IC_{50}$ of $4.51{\pm}0.76{\mu}g/mL$), KATO-III (IC50 of $6.06{\pm}0.39{\mu}g/mL$), Hep-G2 ($IC_{50}$ of $0.71{\pm}0.22{\mu}g/mL$), Chago I ($IC_{50}$ of $0.81{\pm}0.18{\mu}g/mL$) and BT474 (IC50 of $4.28{\pm}0.14{\mu}g/mL$) cell lines. Early apoptosis (programmed cell death) of SW620 cells was induced by the cardol containing F45 fraction at the $IC_{50}$ and $IC_{80}$ concentrations, respectively, within 2-6 h of incubation. In addition, the F45 fraction induced cell cycle arrest at the G1 subphase. Conclusions: Indonesian stingless bee (T. incisa) propolis had moderately potent in vitro anticancer activity on human cancer derived cell lines. Cardol or 5-pentadecyl resorcinol was identified as a major active compound and induced apoptosis in SW620 cells in an early period (${\leq}6h$) and cell cycle arrest at the G1 subphase. Thus, cardol is a potential candidate for cancer chemotherapy.

• IMMUNE NETWORK
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• v.9 no.4
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• pp.122-126
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• 2009

Transforming growth factor-$\beta$ (TGF-$\beta$) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-$\beta$ facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-$\beta$ antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-$\beta$ antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic $CD8^+$ Tcells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-$\beta$ on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.