[The world's population trend].
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Demography↗
Biomedical subjects
Q Shen
Publications and source records attributed to Q Shen.
Kynostatin and 17beta-estradiol prevent the apoptotic death of human neuroblastoma cells exposed to HIV-1 protease.
A significant number of adult male patients with acquired immunodeficiency syndrome develop cerebral atrophy and progressive brain disorders such as dementia complex and neuropsychiatric problems. Upon entering the brain via activated macrophages or microglias, the human immunodeficiency type 1 virus (HIV-1) may produce cytotoxic factors such as HIV-1 envelope protein (gp120) and protease. Owing to significant proteolysis of nonviral proteins, the protease derived from HIV-1 may be detrimental to brain cells and neurons. Our results revealed that HIV-1 protease, at nanomolar concentrations, was as potent as gp120 in causing neurotoxicity in human neuroblastoma neurotypic SH-SY5Y cells. As shown by the Oncor ApopTag staining procedure, HIV-1 protease significantly increased the number of apoptotic cells over the serum-free controls. Moreover, HIV-1 protease-induced neurotoxicity was blocked by a selective protease inhibitor, kynostatin (KNI-272). Antioxidants such as 17beta-estradiol, melatonin, and S-nitrosoglutathione also prevented protease-induced neurotoxicity. These findings indicate that oxidative proteolysis may mediate HIV-1 protease-induced apoptosis and the degeneration of neurons and other brain cells. Centrally active protease inhibitors and antioxidants may play an important role in preventing cerebral atrophy and associated dementia complex caused by HIV-1.
Antioxidants↗
Hypertrophic scar tissues and fibroblasts produce more transforming growth factor-beta1 mRNA and protein than normal skin and cells.
Transforming growth factor-beta1 is a well-known fibrogenic cytokine produced by many types of cells including dermal fibroblasts. To investigate whether this fibrogenic cytokine is involved in development of hypertrophic scar, transforming growth factor-beta1 gene expression was evaluated in small skin samples. Because a sufficient quantity of normal skin from patients with hypertrophic scar is not readily available, a reverse transcription-polymerase chain reaction technique was used. Quantitation of gene expression by reverse transcription-polymerase chain reaction is difficult partly due to the lack of suitable complementary RNA standards. We have established a convenient, reliable procedure to construct an internal standard for transforming growth factor-beta1 starting with a gene specific polymerase chain reaction product. After digestion of the polymerase chain reaction product with endonuclease, a small piece of cDNA from human procollagen alpha1(I) cDNA with compatible ends was inserted into the polymerase chain reaction-DNA fragment. The recombinant cDNA was re-amplified by polymerase chain reaction and subcloned into a plasmid containing bacteriophage T7 and T3 promoters. Complementary RNA was prepared from the recombinant plasmid and amplified by reverse transcription-polymerase chain reaction together with the tissue or cellular RNA. After amplification, the products were electrophoresed in an agarose gel containing ethidium bromide. The bands for internal standard and transforming growth factor-beta1 mRNA were scanned, digitized, and plotted against the amount of internal standard complementary RNA added in the reverse transcription-polymerase chain reaction. The number of mRNA molecules/cell was calculated. We examined the transforming growth factor-beta1 mRNA in hypertrophic scar tissue and in normal skin and found that hypertrophic scar tissues expressed five-fold more transforming growth factor-beta1 mRNA than normal skin per unit of wet weight. We used this procedure to quantitate transforming growth factor-beta1 mRNA expression in 5 pairs of fibroblast cultures derived from hypertrophic scar and normal skin. The results showed that hypertrophic scar fibroblast cultures contain significantly more molecules of mRNA for transforming growth factor-beta1 than normal cells (116 +/- 6 vs. 97 +/- 7, p = 0.017, n = 5). These results were supported by Northern analysis for transforming growth factor-beta1 mRNA in the cells and enzyme-linked immunosorbent assay for TGF-beta1 protein in fibroblast-conditioned medium. In conclusion, hypertrophic scar tissue and fibroblasts produce more mRNA and protein for transforming growth factor-beta1, which may be important in hypertrophic scar formation. The construction of the gene specific internal standard for reverse transcription-polymerase chain reaction is a simple and reliable procedure useful to quantitate gene expression in a small amount of tissue or number of cells.
Biopsy, Needle↗
PTP1B inhibitors from Saussrurea lappa.
A new lignan glycoside, named 1,5-dihydroxypinoresinol-4'-O-beta-d-glucopyranoside (1), has been isolated from the EtOH extract of the roots of Saussurea lappa, together with twenty known compounds: (+)-1-hydroxypinoresinol-1-O-beta-D-glucopyranoside (2), fraxiresinol-4'-O-beta-D-glucopyranoside (3), (-)-olivil-4''-O-beta-D-glucopyranoside (4), 4-allyl-2,6-dimethoxybenzene-1-O-beta-D-glucopyranoside, syringin, costunolide-15-O-beta-D-glucopyranoside, chlorogenic acid, aloe-emodin-8-O-beta-D-glucopyranoside (5), rhein-8-O-beta-D-glucopyranoside (6), chrysophanol (7), emodin, dehydrocostus lactone, costunolide, beta-costic acid, reynosin, arbusculin A, alpha-cyclocostunolide, beta-cyclocostunolide, santamarine and magnolialide. Three anthraquinones (5-7) showed moderate bioactivity against human Protein Tyrosine Phosphatase 1B (hPTP1B) in vitro.
Anthraquinones↗
Quantitative image analysis of oesophageal squamous cell carcinoma from the high-incidence area of China, with special reference to tumour progression and papillomavirus (HPV) involvement.
BACKGROUND: Despite much research effort, the major prognostic factor of oesophageal squamous cell cancer (ESCC) remains the pathological stage of the disease as defined by the TNM classification, whereas tumour grading is of limited value in this respect, mainly due to its low reproducibility. A better means for disease prognostication based on improved understanding of the pathogenetic mechanisms is urgently required. MATERIALS AND METHODS: Among the cohort of 700 ESCC patients from the high-incidence area of China, previously subjected to extensive testing for Human papillomavirus (HPV) involvement by in situ hybridization (ISH) and PCR, a group of 273 patients was randomly selected for analysis of the primary tumour, adjacent mucosa and regional lymph nodes, by histopathology and quantitative image analysis. All these and the HPV data were subjected to extensive univariate and multivariate analysis to disclose independent predictors of progressive disease. RESULTS: For the analyses, the tumours were graded into two categories: well-moderately and poorly-differentiated. HPV DNA was detected in 116 (18.9%) of the carcinomas by ISH and in 15.2% by PCR. In univariate analysis, lymph node status (considered as the surrogate marker of progressive disease) was significantly (p < 0.01) predicted by the following nuclear parameters: nuclear area, G0/G1 ratio, HPV DNA status, integrated optical density (IOD), mean optical density (MOD) and S-Phase. In multivariate (stepwise backward LR) analysis, 6 variables remained as independent predictors of disease progression (at p < 0.05 level), the three most significant ones being nuclear perimeter, nuclear roundness and equivalent diameter (p < 0.01). CONCLUSION: A series of quantitatively measured nuclear parameters seem to bear a close correlation with ESCC differentiation and progression in univariate analysis and some of these variables proved to be significant independent predictors of disease progression in multivariate modelling as well. These data clearly advocate the use of quantitative image analysis in searching for additional prognostic factors of ESCC.
Carcinoma, Squamous Cell↗
Evaluation of HPV, CMV, HSV and EBV in esophageal squamous cell carcinomas from a high-incidence area of China.
BACKGROUND: Certain viruses, notably human papillomavirus (HPV), cytomegalovirus (CMV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV), are known to produce tumors in animals and cell transformation in vitro and they have been implicated in the pathogenesis of human cancers. All these viruses are also known to infect the esophagus. This study was aimed to determine whether these viruses play any causal role in the etiology of esophageal squamous cell carcinoma. MATERIALS AND METHODS: A series of 103 esophageal squamous cell carcinomas derived from patients in the high-incidence area of northern China were analyzed by DNA in situ hybridization and polymerase chain reaction (PCR) for the presence of HPV DNA sequences and, using immunohistochemistry, for the demonstration of CMV, HSV and EBV infections. RESULTS: Six (5.8%) of the 103 tumors were found to contain HPV 16, 18 or 30 DNA sequences. HPV types 6, 11 and 53 were not detected in any of the cases. Amplified HPV DNA sequences were found in 17 out of 101 (16.8%) carcinoma specimens by PCR with L1 consensus primers. None of the 103 carcinomas tested was immunohistochemically positive for CMV, HSV or EBV. CONCLUSION: Our results confirmed the HPV involvement in esophageal carcinomas and provided further evidence to support a causal association of HPV infection with esophageal squamous cell carcinoma. However, the three herpesviruses, CMV, HSV and EBV, are highly unlikely to be involved in the pathogenesis of this malignancy in the high-incidence area of China.
Adenocarcinoma↗
Intratumoral injection of boiling carboplatin (BCBP) solution for treatment of liver cancer in the animal model.
BACKGROUND/AIMS: To develop a new modality of local hyperthermal chemotherapy for liver cancer. METHODOLOGY: Carboplatin solutions of various concentrations were heated at 60 degrees C, 80 degrees C and 100 degrees C, and carboplatin content, pH value and ultraviolet absorption spectrum were assayed before and after heating. By establishing BALB/c murine model of subcutaneous transplant liver cancer, intratumoral injection of boiling carboplatin solution (group A), 45 degrees C carboplatin solution (group B), room-temperature carboplatin solution (group C), boiling distilled-water (group D) and room-temperature distilled-water (control group) was carried out, and tumor growth curve, tumor regression rate and pathohistological features following treatment were evaluated. RESULTS: Carboplatin content remained stable, ultraviolet absorption spectrum presented no remarkable changes and pH value showed a slight decline after being heated for up to 20 min. Following treatment, all 16 tumors in group A were completely regressed up to day 21. In groups B, C and control group, no tumors became fully regressed and a size of 1.98 +/- 1.11 cm2, 1.50 +/- 0.58 cm2 and 4.83 +/- 0.37 cm2 was presented on day 21, respectively. In group D, though all tumors grossly disappeared during the early post-treatment days, 12 out of 16 recurred on day 21. The tumor regression rate in group A was significantly lower as compared with that of groups B, C, D and control group (all P < 0.01). Histological examination revealed massive necrosis with some degenerated tumor cells at the tumor margin in groups A and D, and only focal necrosis with more viable tumor cells at the center and margin in groups B and C on post-treatment day 1 and 3. Twenty-one days after injection, all tumors in group A presented complete necrosis and were partly replaced by fibrotic tissue. Except for 4 regressed tumors in group D which had the same histological features as those in group A, all other tumors in groups B, C, D and control group presented the same histological features as those untreated. CONCLUSIONS: Carboplatin solution remained stable at boiling status. Intratumoral injection of boiling carboplatin solution could completely devitalize liver cancer tissue via synergistic effects of direct tumoricidal role of heat and the heat-enhanced tumoricidal role of carboplatin.
Animals↗
Cytokeratin expression patterns as an indicator of tumour progression in oesophageal squamous cell carcinoma.
Recent studies point out that cytokeratins (CKs) are involved in dynamic cell remodeling during cancer progression and particularly, CK expression patterns have been associated with invasion and metastasis. In oesophageal squamous cell cancer (ESCC), lymph node (LNN) metastasis is an important step in disease progression, invariably associated with an ominous prognosis. To assess whether specific CK expression patterns could represent reliable markers of tumor progression, a series of 111 ESCCs (59 lymph node-positive, 52-negative) derived from the high- incidence area of Linxian (Northern China), were subjected to immunohistochemical (IHC) analysis with an extensive panel of CK antibodies. Statistically significant differences were observed for CK18 (p=0.01), CK19 (p=0.04) and PKK1 (p=0.02) expression between the LNN-negative and LNN-positive ESCCs. Furthermore, significant correlation between specific CK distribution pattern and progressive disease (i.e., LNN metastasis) was evidenced. The results suggest that CK8, CK18 and CK19 expression and distribution pattern could be of predictive value as a marker of disease progression as defined by the appearance of lymph node metastases in oesophageal squamous cell cancer.
Adult↗
Novel strategies for the selection of cells expressing human adenosine deaminase and their application in experimental gene therapy protocols.
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Adenosine Deaminase↗
Esophageal cytology and subsequent risk of esophageal cancer. A prospective follow-up study from Linxian, China.
This paper reports a 15-year follow-up study of 12,693 persons in Linxian, China, who were originally screened by esophageal balloon cytology in 1974. The purpose of the study was to evaluate the ability of esophageal balloon cytology to identify individuals at increased risk for developing esophageal cancer. Age, sex and cytologic diagnoses were obtained from the original 1974 records, and information on vital status, cancer experience and potential confounding risk factors was collected from interviews and medical abstracts in 1989. A total of 1,162 incident cases of esophageal cancer and 993 deaths due to esophageal cancer were identified and used in this analysis. The follow-up study showed that the risk of esophageal cancer incidence and mortality increased in parallel with the presumed severity of the 1974 Chinese cytologic diagnoses. After adjusting for potential confounding factors, the relative risks (and 95% confidence intervals) for esophageal cancer incidence, by cytologic diagnosis, were: normal, 1.00; esophagitis, 1.52 (1.07-2.14); hyperplasia, 1.17 (1.02-1.33); dysplasia 1, 1.53 (1.10-2.14); dysplasia 2, 1.89 (1.47-2.41); and suspicious for cancer, 5.77 (3.79-8.80). These results suggest that esophageal balloon cytology, as performed and interpreted in Linxian in 1974, successfully identified individuals at increased risk for esophageal cancer.
Adult↗
p53 overexpression and human papillomavirus (HPV) infection in oesophageal squamous cell carcinomas derived from a high-incidence area in China.
Oesophageal epithelium is frequently exposed to various carcinogens and mutagens, many of which may cause p53 gene mutations. The epithelium can also be infected with human papillomavirus (HPV), the E6 protein of which may complex with p53 protein and facilitate its degradation. To identify HPV infection and p53 overexpression in oesophageal cancer, we performed immunohistochemical analysis using CM-1 anti-p53 antibody and DNA in situ hybridization with biotinylated HPV DNA probes on paraffin-embedded sections in 36 patients with oesophageal squamous cell carcinomas derived from a high-incidence area in northern China. Samples from cancer tissue, adjacent epithelia, regional lymph nodes as well as resection margins were examined. p53 protein accumulation was detected in 55.6% (20/36) of cancer samples, in 20% (1/5) of hyperplastic epithelium, in 20% (2/10) of dysplastic lesions as well as in 67% (2/3) of carcinoma in situ lesions adjacent to invasive carcinomas. HPV DNA sequences were demonstrated in 3 patients (8.3% of the total). Two of these HPV-positive carcinomas were immunohistochemically negative for p53 and one was weakly positive. Our results suggest that p53 overexpression is frequently found in oesophageal carcinomas and that p53 alteration may be an early event in esophageal carcinogenesis. HPV and elevated p53 are not mutually exclusive events, instead they can coexist in some oesophageal squamous cell carcinomas.
Adult↗