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Biomedical subjects

Z Pan

Publications and source records attributed to Z Pan.

At least 73 records · Page 4Linked to original sources

[Relationship between the expression of transforming growth factor beta type I receptor (T beta R I) and prognosis of hepatocellular carcinoma (HCC)].

OBJECTIVE: To study the expression of T beta R I in HCC tissues and its clinical significance. METHODS: Expressions of T beta R I in HCC tissues (HT, n = 30) and surrounding liver tissues(HST, n = 30) as well as four normal control liver tissues (CIT, n = 4) were determined by radioligand binding assay with 125I TGF beta 1 as the ligand. Relationships between some clinicopathological parameters of HCC and the relative expression rates of T beta R I in HCC were studied. RESULTS: Compared with that in HST, the expression of T beta R I HT was significantly lower than in HST and CIT (P < 0.01). The expression of T beta R I in HST is similar to that in CIT. T beta R I relative expression rates in the group of no capsule or capsule invaded and in the group of tumor embolus were markedly decreased (P < 0.05). No close relationships were found between the T beta R I relative expression rate and age, sex, HBV infection, liver cirrhosis, AFP concentration, tumor diameter, tumor number, tumor differentiation as well as tumor embolus. CONCLUSIONS: The low expression of T beta R I in HT may be one of the key event which promote the HCC malignant growth by protecting them against the growth inhibition effect of active TGF beta. The T beta R I relative expression rate may be related to the prognosis of HCC.

Activin Receptors, Type I↗

A phase I study of paclitaxel, etoposide, and cisplatin in extensive stage small cell lung cancer.

This Phase I study was designed to determine the maximally tolerated dose (MTD) of paclitaxel with standard doses of cisplatin and etoposide for patients with untreated extensive stage small cell lung cancer (SCLC). Secondary objectives were to determine the toxicities, response rate, response duration, and overall survival in this cohort. Twenty-eight SCLC patients were enrolled into four dose levels. All patients received a fixed dose of cisplatin at 80 mg/m2, i.v., day 1. The first group received etoposide 50 mg/m2, i.v. day 1 and 100 mg/m2 p.o., days 2-3, whereas all subsequent groups received etoposide 80 mg/m2, i.v., day 1 and 160 mg/m2, p.o., days 2-3. The paclitaxel starting dose was 135 mg/m2, i.v., over a 3-h period and was escalated to 175 and 200 mg/m2. Cycles were repeated every 21 days for a maximum of six cycles. Granulocyte-colony stimulating factor was not given prophylactically but was allowed in subsequent cycles according to the American Society of Clinical Oncologists guidelines. All 28 SCLC patients were evaluable for toxicity, and 23 patients were evaluable for response. Myelosuppression was the major toxicity, with grade 4 neutropenia occurring in 23 of 28 patients (82%), but febrile neutropenia was uncommon and developed in 4 patients (14%). Grade 4 thrombocytopenia and anemia were rare, occurring as isolated events in one patient each. Dose-limiting peripheral neuropathy was observed at a paclitaxel dose of 200 mg/m2. Grade 4 nausea/vomiting and diarrhea were also noted at this dose level. Five patients had complete responses (22%), and 14 patients had partial responses (61%). The overall response rate was 83% with a median time to progression of 7.5 months, a median survival of 10 months, and a 1-year survival rate of 39%. This three-drug combination of paclitaxel with cisplatin and etoposide is active with acceptable toxicity. Neurotoxicity was dose limiting at 200 mg/m2 of paclitaxel. Neutropenia was frequent but not associated with significant morbidity. The recommended doses for future clinical trials are 175 mg/m2 paclitaxel, i.v., over a 3-h period on day 1 with 80 mg/m2 cisplatin, i.v., on day 1 and 80 mg/m2 etoposide, i.v., on day 1 and 160 mg/m2 p.o. on days 2 and 3 with growth factor support. The Southwestern Oncology Group has instituted a Phase II study with this dose schedule.

Adult↗

[A study on proliferation and differentiation of limbal stem cells].

OBJECTIVE: To study the proliferation and differentiation of limbal stem cells (LCs) in vitro and examine the effects of epithelial growth factor (EGF) on cell proliferation. METHODS: The cells were cultured in DMEM/F12 medium. The proliferation and differentiation of cultured cells were studied by colony-forming efficiency (CFE), immunohistochemistry staining and Western blot examination. RESULTS: LCs could be passaged 5 times in this culture condition. The CFE of stem cells was (5.07 +/- 2.35)%, while that of the central epithelial cells (CCs) was (1.12 +/- 0.86)%. The rates of freezing and recovery were (0.43 +/- 0.22)% in LCs and (0.16 +/- 0.07)% in CCs. Limbal stem cells could be stimulated to proliferate better by EGF at the concentration of 5 and 20 ng/ml. The staining of keratin 3 (K3) to stem cells in the primary culture was negative, but positive in the second and third passages. However, the expression of K3 by Western blot examination was positive in the primary and second passages but negative in the fourth one. CONCLUSION: It is better for limbal stem cells to be used for transplantation and drug screening in the primary culture.

Animals↗

[Genetic polymorphism and susceptibility to occupational chronic manganism: a case-control study].

OBJECTIVE: In a case-control study, the possible genetic factors relevance to occupational chronic manganism were investigated. METHODS: Forty-nine manganisms who were welders and ferromanganese smelters occupationally exposed to manganese dust and fume from three metallurgical industries, and fifty unrelated healthy control subjects who were working same workshops were recruited. The subjects were matched for sex, age, cigarette and alcohol intake. The manganese exposure duration was also matched in this case-control study. Genetic polymorphism of cytochrome P450 2D6L (CYP2D6L) gene and NAD(P)H: quinone oxidreductase (NQO1) genes from all subjects were investigated. The mutations of CYP2D6L gene located exon 6 were analyzed by a polymerase chain reaction (PCR)-based DNA amplification combined with Hha I restriction fragment length polymorphism (RFLP). The substitution of 609(C-T) at exon 6 of DT-diaphroase gene was analyzed by PCR combined Hinf I RFLP. RESULTS: The frequency of polymorphic allels, a mutation of CYP2D6, was significantly lower in patients with manganism (16.3%) than that of the controls (29.0%). A significant association was also found between the homozygote variant of CYP2D6L gene and occupational manganism. These results suggest that the CYP2D6 gene might be one of the susceptibility genes for Mn-induced neurotoxicity. The allele and genotype frequencies of NQO1 gene were similar in the manganism cases and control subjects. CONCLUSION: It is possible that CYP2D6 gene may be a valuable susceptibility biomarker responded to Mn-induced central nervous system disorders in workers exposed to manganese.

Adult↗

[Long-term follow-up result of partial laryngectomy in senile patients with laryngeal carcinoma].

OBJECTIVE: To study the long-term follow-up result of laryngectomy with reservation of laryngeal function in senile patients. METHODS: Ninety-nine patients who were above 65 years old and underwent partial laryngectomies from 1986 to 1990 were summarized. Among them, 14 cases underwent vocal cord resection, 31 vertical hemilaryngectomy, 15 horizontal supraglottic hemilaryngectomy, 2 horizontal glottic laryngectomy, 22 horizontovertical (3/4) laryngectomy, 5 subtotal laryngectomy, 10 total laryngectomy with cricopharyngeal anastomosis. RESULTS: All patients had their phonation and respiration restored. Decannulation rate was 91.9%. No death occurred during the operation. No severe postoperative complications were found. 3.5-year survival rates were 76.7% and 75.5% respectively. CONCLUSION: Senility is not a contraindication for laryngectomy with reservation of laryngeal function. The key points are that surgeons should master indications correctly and improve surgical skill to decrease postoperative complications.

Aged↗

[Cervical lymph node metastasis and recurrence in supraglottic carcinoma after operation].

OBJECTIVE: To evaluate the regional control efficacy of elective neck dissection (END) in patients with supraglottic carcinoma. METHODS: The incidence of cervical recurrences of 582 patients with supraglottic carcinoma treated in this hospital from 1981 to 1993 were retrospectively reviewed. RESULTS: Three hundred and ninety-two cases (67.35%) of this group had T3 and T4 primary lesions. Among them, 147 cases (37.50%) had positive nodes(N+) and this accounted for 86.47% (147/170) of all N+ patients. Ipsilateral or bilateral cervical recurrence occurred in 33 of 126 (26.19%) node negative (N0) cases who had not had neck dissection and 30 of them (90.90%) were among T3 and T4 groups. However, Contralateral lymph node recurrence occurred only in 40 of 286(13.99%) N0 cases who had had END and 30 of them (75%) were among T3 and T4 groups. There were 163 cases who were readmitted and received surgery again for different purposes. The three and five year survival rates in the second stage END group were 86.67% and 77.78%, in metastasis group 64.81% and 32.50%, in recurrent group 33.33% and 30.77% respectively. There were significant differences in survival rates among these groups. CONCLUSION: Patients underwent elective neck dissection achieved better survival than those on "wait and watch" policy and salvage surgery. Elective neck dissection is recommended for the treatment of supraglottic carcinoma, especially for the T3 and T4 diseases.

Adult↗

[Studies on data compression of 1-D NMR spectra using wavelet transform].

The multiresolution signal decomposition (MRSD) algorithm based on wavelet transform was applied to the compression of 1-D NMR spectra. A NMR spectrum which was composed of 32768 data points was investigated and the spectrum can be completely reconstructed with the residual square deviation (RSD) being as small as 2.7769 x 10(-4) when the spectrum was compressed to 512 data points. The relationship among the RSD and the different wavelet function, number of decomposiion and the compression ratio was also discussed.

English Abstract↗

KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.

The M-current regulates the subthreshold electrical excitability of many neurons, determining their firing properties and responsiveness to synaptic input. To date, however, the genes that encode subunits of this important channel have not been identified. The biophysical properties, sensitivity to pharmacological blockade, and expression pattern of the KCNQ2 and KCNQ3 potassium channels were determined. It is concluded that both these subunits contribute to the native M-current.

Adult↗

Cloning of a mammalian elk potassium channel gene and EAG mRNA distribution in rat sympathetic ganglia.

1. Three new members of the EAG potassium channel gene family were identified in rat and the complete coding sequence of one of these genes (elk1) was determined by cDNA cloning. 2. The elk1 gene, when expressed in Xenopus oocytes, encodes a slowly activating and slowly deactivating potassium channel. 3. The elk1 gene is expressed in sympathetic ganglia and is also expressed in sciatic nerve. 4. Six of the seven known EAG genes were found to be expressed in rat sympathetic ganglia, suggesting an important functional role for these channels in the sympathetic nervous system.

Animals↗

Aspirin inhibition and acetylation of the plant cytochrome P450, allene oxide synthase, resembles that of animal prostaglandin endoperoxide H synthase.

The enzymatic reactions leading to octadecanoid lipid signaling intermediates in plants are similar to those of animals and are inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) such as salicylic acid and aspirin. In animals, NSAIDs inhibit the cyclooxygenase (COX) activity of prostaglandin endoperoxide H synthase, which ultimately blocks the formation of prostaglandins. In plants, NSAIDs block the formation of 12-oxo-phytodienoic acid and jasmonates, which are the equivalent signaling compounds. In this study we show that NSAIDs act as competitive inhibitors of allene oxide synthase (AOS), the cytochrome P450 that initiates plant oxylipin synthesis. We also show that aspirin causes the time-dependent inhibition and acetylation of AOS, which leads the irreversible inactivation of this enzyme. This inhibition and acetylation superficially resembles that observed for the inactivation of COX in animals. In AOS, aspirin acetylates three serine residues near the C-terminal region that appear to be highly conserved among AOS sequences from other plants but are not conserved among "classical" type P450s. The role of these serine residues is unclear. Unlike animal COX, where acetylation of a single serine residue within the substrate channel leads to inactivation of prostaglandin endoperoxide H synthase, the three serine residues in AOS are not thought to line the putative substrate channel. Thus, inhibition by aspirin may be by a different mechanism. It is possible that aspirin and related NSAIDs could inhibit other P450s that have motifs similar to AOS and consequently serve as potential biochemical targets for this class of drugs.

Acetylation↗

A phase I study of daily carboplatin and simultaneous accelerated, hyperfractionated chest irradiation in patients with regionally inoperable non-small cell lung cancer.

PURPOSE: This Phase I study was designed to determine the maximally tolerated dose (MTD) of daily low dose carboplatin with concurrent accelerated hyperfractionated radiotherapy (AHFX) in patients with locally advanced non-small-cell lung cancer. Patients also received consolidation chemotherapy with carboplatin. Secondary objectives were to determine the response rate, response duration, sites of first relapse, and survival. METHODS AND MATERIALS: Thirty patients received daily carboplatin at doses of 25 or 30 mg/m2. Concurrent radiotherapy was given in 1.5 Gy fractions twice daily for a total dose of 60 Gy. Following chemoradiotherapy, patients received four cycles of carboplatin at 350 mg/m2. RESULTS: Grade 4 esophagitis developed in 2 of 6 (33%) patients receiving 30 mg/m2 of daily carboplatin and was dose limiting. The remaining 24 patients received carboplatin at 25 mg/m2, with 3 patients developing Grade 4 esophagitis (13%). One of 22 patients who received consolidation carboplatin developed Grade 4 thrombocytopenia. An objective response was observed in 70% of patients (2 complete and 17 partial). Sites of failure were local (7 patients), distant (7 patients), and both (3 patients). The median time to progression was 8.3 months, with a median survival time of 18.3 months. The 1- and 2-year survival rates were 63 and 49%, respectively. CONCLUSIONS: Esophagitis was dose limiting when 30 mg/m2 of daily carboplatin was administered with AHFX. At the MTD of 25 mg/m2 of daily carboplatin plus AHFX followed by four cycles of carboplatin, the regimen was shown to be safe and as active or more active than other regimens. Thus, further studies with this regimen are warranted.

Adult↗

Malignancy detection by molecular cytogenetics in clinically normal mucosa adjacent to head and neck tumors.

OBJECTIVE: To identify the potential use of chromosome imbalances as biomarkers for tumorigenesis in head and neck squamous cell carcinoma (HNSCC) by fluorescence in situ hybridization (FISH). DESIGN: In this case-control study, chromosome copy numbers were assessed in dual-target, dual-color FISH assays using DNA probes specific for 14 human chromosomes (1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 15, 17, X, and Y) applied to exfoliated epithelial cells. SETTING: University medical center. PATIENTS: We examined 20 cell brushings (from 10 primary tumors and 10 clinically normal margins) collected from 10 patients with HNSCC and compared these with cell brushings from the oral cavity of 10 nonsmoker and 10 smoker control subjects. INTERVENTION: None. MAIN OUTCOME MEASURE: Chromosomal aneuploidy. RESULTS: Specimens from nonsmokers displayed greater than 91% of cells with normal signals, indicating high analytical sensitivity for the probes. Specimens from smokers demonstrated large variability without significant imbalance (P>.05) compared with those from nonsmokers. Tumor specimens from patients with HNSCC displayed significant chromosomal imbalance (P<.05) for all probes except chromosome Y. Similar imbalance, although in lower frequency, was found in all clinically normal adjacent mucosa specimens. CONCLUSIONS: Interphase FISH demonstrated great applicability in detecting chromosome imbalance associated with malignancy in HNSCC and clinically normal adjacent cells, thereby detecting subclinical tumorigenesis. A panel of chromosome probes (chromosomes 3, 8, 9, and 10) is proposed as an efficient and sensitive additional tool for future routine screening of tumor margins and potential diagnosis of residual disease in HNSCC.

Adult↗

The presence of masked antiribosomal P autoantibodies in healthy children.

OBJECTIVE: To determine if antiribosomal P (anti-P) autoantibodies are present in healthy children. METHODS: Sera from healthy children were screened for anti-P by conventional enzyme-linked immunosorbent assay and immunoblot techniques. Sera were also treated with immobilized ribosomal P antigens on nitrocellulose strips; affinity-purified fractions were tested for anti-P by high-sensitivity immunoblot. The relative binding affinities were compared for affinity-purified anti-P antibodies from healthy children and adults, and patients with systemic lupus erythematosus. IgG fractions of anti-P-depleted sera from healthy children were assessed for inhibition of autologous anti-P activity. RESULTS: Conventional serologic screening showed no IgG nor IgM anti-P in 88 untreated sera. IgG anti-P were unmasked in all 79 sera treated by the membrane batch affinity technique. IgM anti-P were identified in 27 of the treated sera; the percentage of positive sera decreased with increasing age (chi(2) for linear trend P = 0.00081). Affinity-purified anti-P from children had relative binding affinities similar to those of anti-P from other groups. Sera from healthy children contained inhibitory IgG antibodies to anti-P. CONCLUSION: These results show that anti-P autoantibodies are present in all healthy children. The majority of these autoantibodies are masked by IgG antibodies, suggesting concordant development of a regulatory network.

Adolescent↗

Peptide mass fingerprint sequence coverage from differently stained proteins on two-dimensional electrophoresis patterns by matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS).

Identification of proteins separated by two-dimensional electrophoresis (2-DE) is a necessary task to overcome the purely descriptive character of 2-DE and a prerequisite to the construction of 2-DE databases in proteome projects. Matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS) has a sensitivity for peptide detection in the lower fmol range, which should be sufficient for an analysis of even weakly silver-stained protein spots by peptide mass fingerprinting. Unfortunately, proteins are modified by the silver staining procedure, leading to low sequence coverage. Omission of glutaraldehyde increased the sequence coverage, but this improved sequence coverage is still clearly below the sequence coverage starting with Coomassie Brilliant Blue (CBB) R-250-stained spots. Other factors additionally seem to modify proteins during silver staining. By decreasing the protein amount, the advantage of very sensitive detection on the gel is lost during identification, because the resulting low sequence coverage is not sufficient for secure identification. Low-quantity proteins can be identified better starting with CBB G-250 or Zn-imidazol-stained proteins. In contrast, for high-quantity CBB R-250-stained spots, a sequence coverage of up to 90% can be obtained by using only one cleaving enzyme, and up to 80% was reached for medium-quantity spots after combination of tryptic digest with Asp-N- and Glu-C digest.

Electrophoresis, Gel, Two-Dimensional↗