Effect of Celecoxib on Apoptosis of Endometrial Carcinoma Cell

Objective:To investigate the effect of Celecoxib on proliferation and apoptosis of the endometrial carcinoma cell HEC-1B and the effect on the expression of Fas and Survivin mRNA.Methods:The inhibition on the growth of human endometrial carcinoma cell HEC-1B was investigated by cell culture and MTT experiment when treated with different concentrations of Celecoxib.The cell apoptosis was detected by flow cytometry and DNA Ladder Electrophoresis.The change of the expression of Fas and Survivin mRNA after the treatment of Celecoxib was detected With RT-PCR.Results:Celecoxib could effectively inhibit the growth of HEC-1B cells and induce apoptosis.Survivin mRNA expression was decreased and Fas mRNA expression was increased after treating with Celecoxib.Conclusion:Celecoxib could inhibit HEC-1B cell proliferation and induce its apoptosis.     

Effect of 5-aza-2’-deoxycytidine on Cell Proliferation of Nonsmall Cell Lung Cancer Cell Line A549 Cells and Expression of the TFPI-2 Gene

Objective: The present study employed 5-aza-2’-deoxycytidine (5-Aza-CdR) to treat non-small cell lung cancer(NSCLC) cell line A549 to investigate the effects on proliferation and expression of the TFPI-2 gene. Methods:Proliferation was assessed by MTT assay after A549 cells were treated with 0, 1, 5, 10 μmol/L 5-Aza-CdR, a specificdemethylating agent, for 24 ,48 and 72h. At the last time point cells were also analyzed by flow cytometry (FCM)to identify any change in their cell cycle profiles. Methylation-specific polymerase chain reaction (MSPCR), realtime polymerase chain reaction(real-time PCR) and western blotting were carried out to determine TFPI-2 genemethylation status, mRNA expression and protein expression. Results: MTT assay showed that the growth ofA549 cells which were treated with 5-Aza-CdR was significantly suppressed as compared with the control group(0 μmol/L 5-Aza-CdR). After treatment with 0, 1, 5, 10 μmol/L 5-Aza-CdR for 72h, FCM showed their proportionin G0/G1 was 69.7±0.99%, 76.1±0.83%, 83.8±0.35%, 95.5±0.55% respectively (P<0.05), and the proportion in Swas 29.8±0.43%, 23.7±0.96%, 15.7±0.75%, 1.73±0.45%, respectively (P<0.05), suggesting 5-Aza-CdR treatmentinduced G0/G1 phase arrest. MSPCR showed that hypermethylation in the promoter region of TFPI-2 genewas detected in control group (0 μmol/L 5-Aza-CdR), and demethylation appeared after treatment with 1, 5,10 μmol/L 5-Aza-CdR for 72h. Real-time PCR showed that the expression levels of TFPI-2 gene mRNA were1±0, 1.49±0.14, 1.86±0.09 and 5.80±0.15 (P<0.05) respectively. Western blotting analysis showed the relativeexpression levels of TFPI-2 protein were 0.12±0.01, 0.23±0.02, 0.31±0.02, 0.62±0.03 (P<0.05). TFPI-2 proteinexpression in A549 cells was gradually increased significantly with increase in the 5-Aza-CdR concentration.Conclusions: TFPI-2 gene promoter methylation results in the loss of TFPI-2 mRNA and protein expressionin the non-small cell lung cancer cell line A549, and 5-Aza-CdR treatment could induce the demethylation ofTFPI-2 gene promoter and restore TFPI-2 gene expression. These findings provide theoretic evidence for clinicaltreatment of advanced non-small cell lung cancer with the demethylation agent 5-Aza-CdR. TFPI-2 may be onemolecular marker for effective treatment of advanced non-small cell lung cancer with 5-Aza-CdR.     

Mechanism of Suppression on Proliferation of QGY Cell by Oxaliplatin

Objective： To observe the effects of oxaliplatin（L-OHP） on proliferation of human hepatoma cell line QGY in vitro and to investigate the mechanism. Methods： The inhibition of proliferation in QGY cell was assayed by MTT-test. Morphologic changes were observed under light microscope and electronic microscope. Distribution of cell cycle and apoptosis were analyzed using flow cytometry. The expressions of cell cycle proteins and apoptosis-associated proteins were detected with immuno-histochemical technique. Results： Oxaliplatin could inhibit the proliferation of QGY cells and the inhibition depended on the exposure time and dose. The cells showed morphologic changes of the early stage of apoptosis under the light microscope： the shrunk round cells, condensed cytoplasma and pycnosis of nucleus. Apoptotic cells and apoptotic body could be found under the transmission electronic microscope. The analysis of cell cycle indicated that oxaliplatin blocked cells at S and G2/M phases and the cells of G0/G1 phase reduced. When treated with oxaliplatin for 72h, the expressions of cyclin A and Bax were up-regulated, mutant type P53, Bcl-2 and Myc were down-regulated, and Fas was not changed. Conclusion： Oxaliplatin could inhibit the proliferation of the hepatoma cell lines. Cells were blocked at S and G2/M phases. The apoptosis was related to the up-regulation of Bax and down-regulation of mutant type P53, Bcl-2 and Myc. Oxaliplatin could not induce apoptosis through the Fas pathway.     

Hyperthermia Enhances Thermal-Neutron–Induced Cell Death of Human Glioblastoma Cell Lines at Low Concentrations of 10B

Purpose: To examine the ability of pre- vs. post-irradiation hyperthermia to enhance the effectiveness of thermal neutrons to kill human glioblastoma cells.Methods and Materials: Human glioblastoma cell lines, T98G, A7, A172, and U 87MG, were exposed to thermal neutrons from the Kyoto University Research (KUR) reactor or to ⁶⁰Co γ-rays. Hyperthermia was tested before and after irradiation of T98G (44°C, 15 min) and A7 cells (44°C, 40 min), and with different concentrations (0–30 ppm) of ¹⁰B-boric acid. The biological end point of all experiments was cell survival measured by a colony formation assay.Results: The relative biological effectiveness (RBE) values of thermal neutrons for these cell lines compared with ⁶⁰Co γ-rays were 1.8–2.0 at their D₀ values. When T98G and A7 cells were heated after thermal neutron irradiation, there was a synergistic effect at low ¹⁰B concentrations (up to 5 ppm for T98G and up to 10 ppm for A7 cells). With high concentrations of boron (10–30 ppm for T98G and 20–30 ppm for A7 cells), hyperthermia and neutron irradiation interact additively rather than synergistically. There was no enhancement when cells were heated before thermal neutron irradiation. These results suggest that the radiosensitizing effect of hyperthermia may be attributed to partial inhibition of the repair of the potentially lethal damage caused by neutron irradiation.     

Progress in Diagnosis and Treatment of Small Cell Carcinoma of the Cervix

Small cell carcinoma of the cervix(SCCC)belongs to the neuroendocrine carcinomas,and it is a rare gynecological tumor of high-potential malignancy.It has a poorer prognosis compared to cervical squamous cancer or adenocarcinoma,and the therapeutic regimen of the disease differs.Diagnosis is based on pathomorphological characteristics,i.e.,the small and round cancer cel s(oat cel)which are uniform in shape and size,with the immunohistochemical marker helpful for diagnosis.Combined therapy is first recommended.Postoperative chemotherapy with platinum/etoposide (PE),vincristine/adriamycin/cyclophosphamide(VAC)and taxel/carboplatin (TP)can markedly improve the prognosis of early SCCC patients.     

Clinicopathologic Observations on Small Cell Carcinoma of the Esophagus

OBJECTIVE To investigate the histogenesis and biological characteristics and factors influencing prognosis of small cell carcinoma of the esophagus(ESCC).METHODS The expression of CK, NSE, Syn, CHr-A and CD56 proteins were detected immunohistochemically in 63 cases of small cell carcinoma of the esophagus.RESULTS The ESCC cases were divided into two groups as follows: a puresmall cell group (28/63) and compound small cell group (35/63). Theimmunohistochemistry results were positive for: CK in 41.3%, NSE in 36.5%,Syn in 90.5%, CHr-A in 60.3% and CD56 in 50.8%. The difference betweenstaining of the pure small cell carcinoma and compound small cellcarcinoma was not statistically significant. The size and depth of tumorinvasion, the positive residual incision edge and lymph node metastasiswere the major factors influencing long-term survival.CONCLUSION Small cell carcinoma of the esophagus is a highly malignanttumor, which expresses neuroendocrine antigens. The histophathologicorigin is still unknown but the non-neuroepithelial origin was accepted in thisstudy.     

Gastrointestinal Mantle Cell Lymphoma—A Tale of Two Endoscopies

INTRODUCTION: Green oncology is a new conceptual and operational paradigm of oncology, which compared to the traditional biomedical model focused on the interest of a single patient and on its exclusive relationship with the doctor, represents a complex evolutionary step towards clinical activities that have to be eco-responsible of the potential current and future impact on the human, professional, structural, technological, and organizational environment, where they arise, as well as on the biosphere. DEFINITION: Green oncology works through ethical and managerial choices that incorporate, besides the traditional criteria of efficiency and effectiveness, the criterion of cultural, economic, environmental, and social sustainability as they are fair, livable, and possible to be realized.     

Expression of SKP2 Protein in Non-small Cell Lung Carcinoma

Objective: To study the expressive characteristics of SKP2 protein in non-small cell lung carcinoma and it is affection to NSCLC patients' prognosis. Methods: The expression of SKP2 protein was detected in 89 NSCLC, 5 benign lung neoplasmas, 5 normal bronchus and lung tissues by Tissue Chip and immunohistochemistry technology. Results: The positive rate of SKP2 protein staining was (23.52±13.57)% in NSCLC tissues, significantly higher than that in benign lung neoplasmas, normal brochus and lung tissues (2.91±1.27)% (P=0.0000<0.001). The expressive level of SKP2 protein in NSCLC tissues was closely related to cell differentiation (P1=0.000<0.001), but not to age, sex, smoking history,pathological type, site, size, lymph node metastasis and TNM stage (each P1>0.05). The survival analysis displayed that the NSCLC patients' 5 years survival rate was lower in positive expression group than that in negative expression group (P1=0.042/0.031<0.05; r=-0.186, P2=0.000<0.001). Conclusion: The positive expression of SKP2 protein may play an enhancement role in the occurrence and development of NSCLC. Moreover, it may be a bad indicator to NSCLC patients' prognosis.     

Inhibitory Effects of α-Pinene on Hepatoma Carcinoma Cell Proliferation

Background: Pine needle oil from crude extract of pine needles has anti-tumor effects, but the effectivecomponent is not known. Methods: In the present study, compounds from a steam distillation extract of pineneedles were isolated and characterized. Alpha-pinene was identified as an active anti-proliferative compound onhepatoma carcinoma BEL-7402 cells using the MTT assay. Results: Further experiments showed that α-pineneinhibited BEL-7402 cells by arresting cell growth in the G2/M phase of the cell cycle, downregulating Cdc25CmRNA and protein expression, and reducing cycle dependence on kinase 1(CDK1) activity. Conclusion: Takentogether, these findings indicate that α-pinene may be useful as a potential anti-tumor drug.     

β-Catenin Alterations in Squamous Cell Carcinoma of the Lip

This study aimed to investigate the correlation between ß-catenin immunoexpression and histopathologicalgrades of lower lip squamous cell carcinoma (LSCC). β-Catenin abnormal expression was found in 29% of thesquamous cells of well differentiated LSCC, 63% of moderately differentiated and 86% of poorly differentiated,and therefor was significantly associated with histological grade (p=0.000). Nuclear β-catenin expression appearedin 5% of the cells and was also correlated with the histological grades (p=0.000). In 14.7% of the cells it waslocalized in the cytoplasm, again correlating with histology (p=0.002). According to this study the expressionof β-catenin is an independent prognostic factor for histological grade and to the tumor differentiation. Thisappears to reflect a structural association and the role of β-catenin in tumor progression.     

Anti-Tumor Effect of CDA-Ⅱ on a Human Glioma Cell

Objective To examine the effect of uroacitide (CDA-II ), an extraction product from normal human urine, on proliferation and differentiation of human glioma SWO-38 cells. Methods The effects of CDA-II on cellular survival and colony formation were determined by MTT and colony-formation assays. The in vivo anti-tumor effect of CDA-II was examined on transplanted SWO-38 cells in nude mice. In addition, the aterations in cell morphology induced by CDA-II were observed by H&E staining. Results Treatment of SWO-38 cells with 1–5 mg/ml of CDA-II for 3 days, resulted in 39.49%± 5.27%~65.05%± 5.89% growth inhibition with an IC₅₀of 2.52 mg/ml. Based on the colony-formation assay, 10 days of CDA-II treatment at a level of 0.3~2.1 mg/ml caused 23.45%± 0.62%~96.22%±1.01% inhibition with an IC₅₀ of 1.03 mg/ml. Furthermore, the inhibitory response was dose-dependent. CDA-II at dosage of 500 mg/kg or 2,000 mg/kg per day for 4 weeks significantly suppressed the growth of human glioma SWO-38 cells in nude mice, with inhibition being 47.77% and 79.94%, respectively (P< 0.05, n=10). H&E staining and light microscopy revealed that CDA-II induced differentiation of the SWO-38 cells. Conclusion CDA-II has a significant anti-tumor effect on the human glioma SWO-38 cells, and is a potential and natural anti-glioma therapeutic reagent. This work was supported by a grant from the National Key Basic Research Program of Science and Technology Ministry of China (973) (No. 2002ccc0400); a grant from Team Collaboration Project of Guangdong Science and Technology Department (No.015012); and the Key Project Foundation in Science and Technology of Guangdong Science and Techology Bureau (No. 2001-E-01-2).     

Non-Clear Cell Renal Cell Carcinoma: Does the Mammalian Target of Rapamycin Represent a Rational Therapeutic Target?

Non-clear cell renal cell carcinomas (nccRCCs) comprise a heterogenous and poorly characterized group of tumor types for which few treatments have been approved. Although targeted therapies have become the cornerstones of systemic treatment for metastatic renal cell carcinoma, patients with nccRCC have been excluded from many pivotal clinical trials. As such, robust clinical evidence supporting the use of these agents in patients with nccRCC is lacking. Here, we review the disparate nccRCC subtypes, the criteria for diagnosis, and the prognoses associated with each subtype, in addition to evaluating the potential use of mammalian target of rapamycin (mTOR) inhibitors in treating patients with nccRCC. Both genetic analyses and preclinical research indicate a central role for mTOR in nccRCC; a therapy that targets this ubiquitous regulator of cellular signaling could prove efficacious across various tumor subtypes. Results from recent studies exploring targeted therapies as both monotherapy and combination therapy have provided early indications of efficacy in patients with nccRCC. Exploratory analyses support further research with the mTOR inhibitors everolimus and temsirolimus in patients with nccRCC. Current clinical practice guidelines support the use of mTOR inhibitors in patients with nccRCC; however, these recommendations are based on low levels of evidence. Further results from randomized, controlled clinical trials are needed to determine the optimal choice of therapy for patients with nccRCC. Results from ongoing clinical trials of mTOR inhibitors and other agents in nccRCC, as well as their impact on the nccRCC treatment paradigm, are eagerly awaited.     

Diagnosis and Treatment of Chromophobe Cell Renal Carcinoma （Report of 3 cases）

OBJECTIVE To study the diagnosis and treatment of chromophobe cell renal carcinoma (CCRC). METHODS Three cases of CCRC were studied by analyzing the results of an operation, by light microscopy, immunohistochemistry, Hale‘s colloidal iron staining and electronmicroscopy (EMC). RFESULTS Doppler ultrasonic and CT features were not specific. Histopathology: Grossly the tumor tissue was homogeneous, light brown in color with central necrotic foci; Light microscopy: Macrocyte, fine reticular cytoplasm with clear cell border; Hale‘s colloidal iron staining: positive; positive EMA, CK19, vimentin, Ckpan, and negative S-100; EMC: numerous intracyto-plasmic membranous small cysts. All patients were followed up for 14.1-31 months (19.7 months on average), one patient had lung metastasis 11 months after resection of a G,~ tumor, two alive patients had no local recurrences and metastases. CONCLUSIONS CCRC is histo-pathologically, immunohistochemically and electron microscopically distinct from other renal cancers. Surgical tumor removal is the best way for treatment. It is probably a type of cancer with low malignant potential and favorable prognosis.     

Value of ^18F-FDG PET in Clinical Staging of Non-Small Cell Lung Cancer

OBJECTIVE To evaluate the feasibility of ^18F-deoxyglucose positron emission tomography (^18F-FDG PET) in the staging of non-small cell lung cancer(NSCLC). METHODS 105 patients with NSCLC had been examined by ^18F-FDG PET before radiotherapy. The results of the ^18F-FDG PET examination were compared with those of CT.RESULTS The staging was changed in 38 patients because of ^18F-FDG PET findings, with PET resulting in upstaging in 31 patients and downstaging in seven patients. Because of distant metastasis detected by PET, 21 patients received palliative treatment. Six of the seven downstaged patients underwent radical surgery, among which the PET findings were concordant with the pathological findings in five patients. Distant metastasis detected by PET elevated the pre-PET stage: at stage 110.0% (2/20), stage Ⅱ 14.3% (3/21) and stage Ⅲ 25.0% (16/64), respectively.CONCLUSION ^18F-FDG PET, by changing clinical staging in 36.2% (38/105) of NSCLC patients, has an impact on treatment strategy in NSCLC patients.     

Plasmacytoid Transitional Cell Carcinoma of Bladder： A Clinico-pathological Study and Review of Literatures

Objective： To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods： Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results： A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion： The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.