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Biomedical subjects

W Y Li

Publications and source records attributed to W Y Li.

At least 37 records · Page 2Linked to original sources

Salvage surgery for recurrent nasopharyngeal carcinoma in anterior marginal miss after radiotherapy.

Nasopharyngeal carcinoma (NPC) is treated primarily by radiotherapy. Marginal miss after radiotherapy is a potential cause for treatment failure in NPC. Anterior marginal miss after irradiation results in recurrent tumors in the nasal cavity outside the nasopharynx. From 1991 to January 1997, 6 recurrent NPCs arising in the anterior marginal miss zone after radiotherapy were confirmed by pathologic and radiologic evaluation. One patient had infiltrating growth of the original NPC tumor into the anterior part of nasal septum, and the other 5 had microscopic extensions from the original NPC tumors into the nasal cavity that were beyond detection by endoscopy or CT scan. In some cases the tumors extended further to include the hard palate or the lacrimal sac. Medial maxillectomy and partial maxillectomy with or without resection of the hard palate were necessary to encompass the extent of the tumors. Surgical margins were free of cancer cells in 5 patients. No further treatment was given in these 5 patients. Another patient with tumor extending to the lacrimal sac received postoperative radiotherapy. Five of the 6 patients survived with no evidence of disease for 8 to 65 months. One patient had distant metastasis 14 months after surgery but was free from tumor at the primary site. Radical surgery can result in good and sustained local control for anterior marginal miss of NPC after radiotherapy.

Adult↗

Prognosis of esophageal squamous cell carcinoma: analysis of clinicopathological and biological factors.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is rather common among the Chinese, but the therapeutic outcome is dismal. Knowledge of the prognostic factors in cancerous patients may influence therapeutic strategy. However, systemic analyses of clinicopathological and biological factors for patients with ESCC are few, and the results are controversial. METHODS: Between 1985 and 1996, 117 patients undergoing en bloc esophagectomy and gastric substitution were enrolled. None had neoadjuvant treatment. Postoperative adjuvant therapy was provided for patients at and beyond stages IIa. Clinical responses were followed routinely. Flow cytometry was used to measure DNA ploidy and synthesis-phase fraction (SPF) of the resected esophageal tissues from all patients. Immunohistochemistry was also used to examine the expression of proliferating cell nuclear antigen (PCNA), epidermoid growth factor receptor (EGFR), HER-2/neu, and p53 in the pathological sections. Clinical correlation was evaluated by chi2 with Fisher's exact test, and survival by log-rank test. RESULTS: The overall survival rates were 74% for 1 yr, 48% for 3 yr, and 38% for 5 yr. TNM tumor staging, the number of diseased lymph nodes (N < or = 3 or N > 3), degree of cell differentiation, DNA ploidy, SPF, and lymphovascular invasion were more useful than biological markers, such as PCNA, EGFR, HER-2/neu, and p53, for the prognosis of ESCC. Multivariate analysis revealed significant correlation of tumor staging and number of diseased lymph nodes with patient survival after surgery. CONCLUSIONS: En bloc esophagectomy may provide a rather satisfactory survival rate for patients with early stage ESCC. However, for patients with distant lymph node metastasis and those with more than three lymph nodes involved, radical surgical resection, even combined with postoperative chemoradiotherapy, cannot improve survival. The prognostic value of biological markers, including PCNA, EGFR, HER-2/neu, and p53, however, is limited.

Adult↗

Detection of Epstein-Barr virus in esophageal squamous cell carcinoma in Taiwan.

OBJECTIVE: Recently, an association between viral infection and the development of esophageal carcinoma has been reported, particularly the human papilloma virus (HPV) and Esptein-Bar virus (EBV). However, geographic variation in carcinogenesis is realized. In this study, we investigate the viral carcinogenesis and the biologic effect of viral infection on esophageal squamous cell carcinoma (ESCC) in Taiwan. METHODS: To determine the association of viral infection (EBV and HPV) with ESCC, we applied polymerase chain reaction (PCR), immunohistochemistry, and in situ hybridization (ISH) to examine 119 surgical specimens from different sites of esophagus in 31 ESCC patients. Additionally, an immunoperoxidase method was used to detect EBV latent membrane protein-1 (LMP-1), p53, CD45RO (UCHL-1), Fas ligand (Fas L), and RNA ISH with oligonucleotide sequences was used to detected interleukin-6 (IL-6) mRNA. RESULTS: By PCR, EBV DNA was detected in 11 cases (35.5%). Expression of EBERs in ESCC was further confirmed with ISH. Nonetheless, no LMP-1 expression was detected. On the other hand, human papillomavirus (HPV) was identified in only one case (3.2%) of ESCC. Furthermore, HPV was located by ISH in the distant normal region rather than in tumor cells. In EBV-positive cases, accumulation of p53 protein was detected in 10 lesions (91%); CD45RO+ lymphocytes together with expressions of FasL and IL-6 were respectively identified in 100%, 63.6%, and 54.5% of 11 EBV-positive lesions. Interestingly, in the EBV-negative cases (n = 20), p53 protein was detected in 40% of lesions; CD45RO 30%; FasL 50%, and IL-6 10%. CONCLUSIONS: In this study, no correlation was found between the presence of EBV in ESCC and the patients' age, sex, as well as survival. Although our results indicate that EBV could be associated with ESCC, the clinical role of EBV in ESCC remains to be determined.

Aged↗

Pharmacokinetics of trimetrexate and dapsone in AIDS patients with Pneumocystis carinii pneumonia.

The objective of this study was to determine the pharmacokinetics of trimetrexate and dapsone in AIDS patients with moderate to severe pneumocystis pneumonia. Trimetrexate, leucovorin, and dapsone were administered for 21 +/- 3 days in the following doses: trimetrexate glucuronate, 45 mg/m2; leucovorin, 20 mg/m2; and dapsone, 100 mg daily. The pharmacokinetics of trimetrexate, dapsone, and dapsone's metabolite, monoacetyldapsone, were determined at three separate periods over the course of treatment. Serial blood samples were obtained over 24 hours after dosing and analyzed for trimetrexate, dapsone, and monoacetyldapsone, and pharmacokinetic parameters were determined. The mean parameters obtained for the early, mid-, and late collection periods were the following: trimetrexate: t1/2 = 8.29, 9.15, 10.00 hr; AUC = 16.85, 22.38, 24.49 mg.hr/l; CI = 5.58, 4.14, 3.96 l/hr, respectively. DDS: t1/2 = 14.99, 16.59, 15.13 hr; AUC = 30.60, 35.29, 36.08 mg.hr/l; CI = 3.82, 3.49, 3.01 l/hr, respectively. Monoacetyldapsone: t1/2 = 20.25, 18.66, 16.32 hr; AUC = 24.05, 24.06, 23.86 mg.hr/l, respectively. No statistically significant changes in pharmacokinetics for trimetrexate or dapsone were observed over the 21 +/- 3 day course of treatment. The results suggest that there are no major interactions between trimetrexate and dapsone when administered together in acutely ill patients.

AIDS-Related Opportunistic Infections↗

Prognostic significance of HER-2/neu overexpression in stage I adenocarcinoma of lung.

BACKGROUND: Even with early diagnosis and adequate resection, the 5-year survival rate for stage I lung cancer patients is around 60% to 70%. Overexpression of HER-2/neu protein is associated with poor prognosis in lung cancers. In this study, we evaluated the expression of HER-2/neu in cancer cells of lung and assessed their clinicopathologic and prognostic significance. METHODS: From 1986 to 1995, clinical data on 42 consecutive patients who underwent complete surgical resection for stage I lung adenocarcinoma were collected. Expression of HER-2/neu in paraffin-embedded tumor samples was determined by immunohistochemistry and scored with a semiquantitative method. RESULTS: Twenty-one of 42 patients were positive for HER-2/neu overexpression in tumor. Compared with patients with low HER-2/neu expression, patients with HER-2/neu overexpression had a significantly higher incidence of early tumor recurrence (p = 0.014). Survival was also significantly better in patients without HER-2/neu overexpression than in those with HER-2/neu overexpression (p = 0.0047). By univariate analysis, HER-2/neu overexpression and poor cell differentiation are two important factors correlated with poor prognosis. CONCLUSIONS: Expression of HER-2/neu oncoprotein in stage I lung adenocarcinoma can predict the tumor's aggressiveness. Early tumor recurrence was frequently detected in patients with HER-2/neu overexpression. We recommend an individualized therapeutic strategy based on the level of HER-2/neu oncoprotein in the tumor cells.

Adenocarcinoma↗

Flow-cytometric DNA content analysis of oesophageal carcinoma. Comparison between tumour and sequential non-tumour mucosae.

The DNA content in oesophageal carcinoma and in sequential non-tumour mucosa was evaluated in 35 patients with oesophageal carcinoma, to explore the hypotheses that DNA distribution pattern and S-phase fraction can reflect malignant potential and that DNA aneuploidy can provide an early-warning signal of developing cancer. DNA flow cytometry was performed on 129 specimens from the tumours and on 119 specimens from non-tumour mucosa. Control specimens from gastric fundus had normal diploid DNA content and low S-phase fraction. Aneuploidy was found in 94.3% of the carcinoma specimens and intratumoral heterogeneity in 54.3%. Of the non-tumour specimens, 43.7% showed aneuploidy and none multiple aneuploidy. Pattern III distribution was present in 8.6% of the tumour specimens but not in non-tumour mucosa, where the incidence of aneuploidy rose with closeness to the tumour (p < 0.001). S-phase fraction was smaller in non-tumour than in tumour specimens (p < 0.0001). The study indicated that histologically tumour-free oesophageal mucosa may have a high malignant potential in patients with oesophageal carcinoma. The relative instability of such mucosa, with aneuploid cells and low S-phase fraction, may facilitate transition to abnormally proliferating cells in response to environmental signals. Cigarette smoking and alcohol may increase the risk of multicentric cancer development.

Adult↗

Lymph node metastasis in squamous cell carcinoma of the intrathoracic esophagus.

BACKGROUND: In esophageal carcinoma lymph node metastasis is one of the most important factors of prognosis. This prospective study evaluated the incidence and extent of lymph node metastasis, and assessed the relationship between the depth of tumor invasion and lymph node metastasis in esophageal carcinoma. METHODS: Between 1985 and 1996, tissue samples from 112 patients undergoing radical esophagectomy and gastric substitution for squamous cell carcinoma of the intrathoracic esophagus were collected. Patients with distant organ metastasis were excluded. All specimens were evaluated and sent for histopathologic examination. RESULTS: In 108 men and four women with a mean age of 63.1 years, the average number of dissected lymph nodes in one surgical procedure, was 30 per person. The most commonly involved nodes were the periesophageal (42.9%) and the perigastric (42.9%) nodes, followed by the recurrent laryngeal nerve (23.8%) and thoracic paratracheal (22.2%) nodes. For tumors in the upper third of the esophagus, the most frequently involved nodal groups were the periesophageal (28.6%) and the paratracheal (28.6%) nodes, followed by the recurrent laryngeal nerve (21.4%) the deep cervical (21.4%), and the perigastric (21.4%) nodes. For tumors in the middle third of the esophagus, the periesophageal nodes (27.3%) were most commonly involved, followed by the perigastric (18.2%) and the subcarina (10.6%) nodes. For tumors in the lower third of the esophagus, the perigastric lymph nodes (37.5%) were the most common nodal metastatic site, followed by the celiac (18.8%) and the recurrent laryngeal nerve (18.2%) nodes. Depth of tumor invasion was also found to correlate significantly with lymph node metastasis (p = 0.0015). CONCLUSIONS: Wide lymph node metastasis between the neck and the upper abdomen occurs frequently in squamous cell carcinoma of the esophagus. For potentially curable esophageal carcinomas, en-bloc esophagectomy with complete locoregional lymph node dissection may provide favorable local control of the lesion and more accurate tumor staging.

Adult↗

Treatment results of 17 patients with diffuse pleural mesothelioma.

Treatment for diffuse pleural mesothelioma is very difficult. A retrospective study is established for analyzing the experiences in management of such a rare but fatal disease. From May 1960 to August 1996, 17 patients underwent treatment for pathologically confirmed malignant pleural mesothelioma at Veteran General Hospital-Taipei. The chart records were carefully reviewed and surgical specimens were reconfirmed by the pathologist. Single or combined treatment protocols with surgery, chemotherapy, and radiotherapy had been used according to the clinical situation. Pathological staging was recorded according to the Butchart staging system. Gender, smoking, asbestos exposure, histology, and survival were analyzed. There were 17 patients in total, including 15 males and 2 females with a mean age of 62 years. The most common symptoms were chest pain, cough, dyspnea and weight loss. For getting definite pathological diagnosis, the most sensitive procedures were video-assisted thoracic biopsy and open lung biopsy. In spite of trying multiple different treatment protocols, disease staging ( p = 0.0186) and the epithelial pathological type ( p = 0.0353) were the significant prognostic factors in our series. Prognosis of diffuse pleural mesothelioma is very poor. It was predominant in nen and no definite relationship with smoking or asbestos exposure was noted in our series, but it was relatively better in patients with early-stage and epithelial-type disease. Further efforts to improve the survival should be delivered on more aggressive cytoreductive surgery with early postoperative concurrent chemo-radiotherapy.

Adolescent↗

In-situ photochemical spectrofluorimetric detection of 9,10-anthraquinone-labeled bovine serum albumin.

Bovine serum albumin (BSA) labeled with 9,10-anthraquinone (AQ) shows a greatly enhanced photochemical fluorometric activity compared with that of free AQ. The spectral characteristics of the photoreduction product of conjugated AQ was investigated and large blue shifts in the excitation and emission bands compared with those of free AQ were observed. The enhancement in the photochemical reactivity can be employed for sensitive detection of labeled BSA by a simple in-situ photochemical kinetic fluorimetric method. The kinetic behavior of the photochemical reaction and the effects of some experimental conditions were investigated. The calibration graph was linear over the range 0-1.8 x 10(-7) M BSA. The detection limit was 1.2 x 10(-10) M BSA and the relative standard deviation was 2.24% for the 1.42 x 10(-8) M BSA (n = 7).

Anthraquinones↗

In-situ photochemical spectrofluorimetric detection of 9,10-anthraquinone-labeled bovine serum albumin.

Bovine serum albumin (BSA) labeled with 9,10-anthraquinone (AQ) shows a greatly enhanced photochemical fluorimetric activity compared with that of free AQ. The spectral characteristics of the photoreduction product of conjugated AQ were investigated and large blue shifts in the excitation and emission bands compared with those of free AQ were observed. The enhancement in the photochemical reactivity can be employed for sensitive detection of labeled BSA by a simple in-situ photochemical kinetic fluorimetric method. The kinetic behavior of the photochemical reaction and the effects of some experimental conditions were investigated. The calibration graph was linear over the range 0-1.8 x 10(-7) M BSA. The detection limit was 1.2 x 10(-10) M BSA and the relative standard deviation was 2.24% for 1.42 x 10(-8) M BSA (n = 7).

Anthraquinones↗

Effect of vehicles and penetration enhancers on the in vitro and in vivo percutaneous absorption of methotrexate and edatrexate through hairless mouse skin.

PURPOSE: Low-dose methotrexate (MTX) is approved for the treatment of recalcitrant rheumatoid arthritis (RA). The objective of this study was to determine the effect of vehicles and penetration enhancers on the percutaneous absorption of MTX and its analog edatrexate (EDAM), and develop transdermal (TD) delivery systems of the drugs for the treatment of RA. METHODS: From previously published pharmacokinetic parameters with low-dose MTX therapy, and considering a 50 cm2 diffusional area, the target steady state in vitro TD flux for MTX was calculated to be 35 micrograms/cm2/hr. Modified Franz diffusion chambers and hairless mouse skin were used for in vitro skin permeation studies. Hairless mice were used for in vivo studies. Delivered amounts of MTX and EDAM were determined by assaying the receiver phase fluid (or blood) with validated reversed phase HPLC methods. RESULTS: Intrinsic partition coefficient of MTX was low (log P = -1.2). Target MTX fluxes of > or = 35 micrograms/cm2/hr were achievable only with 1-15% (v/v) Azone in propylene glycol (PG). Flux of EDAM (85 micrograms/cm2/hr) was higher than MTX from an isopropyl alcohol (IPA)-5% (v/v) Azone system. Clinically significant steady state in vivo blood concentration of MTX and EDAM was achieved using delivery systems containing > or = 2.5% Azone in PG. Area under the drug concentration-time curves (AUC0-24 hr) for MTX were 2379 and 3534 ng*hr/ml from PG-2.5% Azone and PG-7.5% Azone systems respectively. AUC0-24 hr of EDAM was 6893 ng*hr/ml using a PG-2.5% Azone system. CONCLUSIONS: Results of this study show the feasibility of using a transdermal delivery system of MTX and EDAM for the treatment of rheumatoid arthritis.

Administration, Cutaneous↗

Application of a novel fluorescence probe in the determination of nucleic acids.

A novel fluorimetric method has been developed for rapid determination of DNA and RNA with hypocrellin A (HA) as a fluorescence probe, based on the fluorescence enhancement of HA in the presence of DNA or RNA. Maximum fluorescence is produced in the pH range 3.4-4.0, with maximum excitation and emission wavelengths at 470 and 600 nm, respectively. Under optimal conditions, the calibration graphs are linear over the range 0-200.0 ng cm-3 for calf thymus DNA and 13.0-200.0 ng cm-3 for yeast RNA, respectively. The corresponding detection limits are 5.0 ng cm-3 for calf thymus DNA and 13.0 ng cm-3 for yeast RNA. The relative standard deviation of six replicate measurements is 4.5% for 100 ng cm-3 calf thymus DNA. DNA could be determined in the presence of 20% m/m yeast RNA. The mechanism for the binding of HA to DNA is also studied.

DNA↗

AgNORs in lung cancer: correlation with DNA ploidy and degree of differentiation.

OBJECTIVE: To assess the usefulness of enumerating argyrophilic nucleolar organizer regions (AgNORs) in assisting with the diagnosis, as well as its correlation with the degree of differentiation and DNA ploidy, in lung cancer. STUDY DESIGN: The specimens, taken from 151 benign and malignant pulmonary tumors, were stained with silver nitrate before the number of AgNORs was counted. DNA ploidy was determined in 58 cases of lung cancers. All cases of adenocarcinoma and squamous cell carcinoma were histologically classified as well, moderately or poorly differentiated. RESULTS: Lung cancers had more AgNORs than benign tumors, and small cell carcinomas had fewer AgNORs than non-NSCLC (P < .001). The mean AgNOR number in adenocarcinoma increased progressively in accordance with poorer differentiation (P < .001). There was no correlation between the number of AgNORs and DNA ploidy. CONCLUSION: Counting AgNORs helps with the differential diagnosis of lung cancers. In adenocarcinoma of the lung, the AgNOR number increases as the degree of differentiation decreases.

Adenocarcinoma↗

Presence of human herpesvirus-like DNA sequence in oral Kaposi's sarcoma. A preliminary PCR study.

DNA sequences closely related to herpesvirus-like sequences have been found in AIDS-associated Kaposi's sarcoma. Subsequent studies indicate that these DNA sequences may be consistently found in AIDS Kaposi's sarcoma and non-AIDS Kaposi's sarcoma from different geographic regions. Oral Kaposi's sarcoma is rare and the specificity of this viral DNA in oral Kaposi's sarcoma and in other oral neoplasms has not been examined. A total of 77 oral neoplasms, including 3 Kaposi's sarcoma specimens from 2 patients with AIDS, were analyzed by polymerase chain reaction for the presence of this herpesvirus-like DNA sequence with the 330-233 primers. All three specimens of oral AIDS-Kaposi's sarcoma from two patients were positive for this DNA sequence. All of the other intraoral lesions including hemangioma, pyogenic granuloma, and various types of epithelial neoplasms, however, had negative reactions. Our results further confirm that oral Kaposi's sarcoma appears to be associated with this herpesvirus-like DNA sequence.

AIDS-Related Opportunistic Infections↗

Malignant lymphoma presenting as tracheal tumor: a case report.

A 66-year-old male presented with dyspnea and cough for 1 month. Fiberoptic bronchoscopy disclosed a huge tumor over the posterior wall of the trachea 1 cm below the vocal cord and biopsy pathology was diffuse, small cleaved lymphoma. Primary malignant lymphoma of the trachea is extremely rare. Its clinical course varies widely, and has no accepted standard of management. We describe herein the whole clinical course of this patient, which is not similar to previous reports. The relation of primary tracheal lymphoma to mucosa-associated lymphoid tissue (MALT) is also discussed.

Aged↗

High-performance liquid chromatographic method for the determination of a novel thymidylate synthase inhibitor, AG 331, in human serum.

AG 331 is a novel thymidylate synthase inhibitor currently in Phase I clinical trial. To determine the pharmacokinetic parameters of AG 3331 in human subjects, a suitable analytical method was developed using high-performance liquid chromatography. Serum and urine samples were prepared using both solid-phase extraction and solvent extraction. Either 4,4'-diaminodiphenyl sulfone or benz[cd]indole-2(1H)-one were used as internal standards for the method. A reversed-phase C18 analytical column completely resolved the drug and internal standard peaks from non-specific substances present in biological matrix. The method was validated for precision, accuracy, and reproducibility in serum and was linear over a concentration range of 50-2000 ng/ml, with a limit of detection of 20.0 ng/ml and a quantifiable limit of 50 ng/ml.

Chromatography, High Pressure Liquid↗

Neuronal membrane conductance activated by amyloid beta peptide: importance of peptide conformation.

Whole-cell voltage-clamp recording and circular dichroism (CD) spectroscopy were used to assess the importance of amyloid beta peptide (A beta) conformation for eliciting homeostatically disruptive membrane conductances in embryonic rat hippocampal neurons. A beta that assumed a random coil conformation when freshly dissolved in water did not alter cell resting ('leak') membrane conductances. In contrast, after several days incubation ('aging'), the same peptide samples became capable of activating a large, rapid onset and potentially toxic increase in leak membrane conductance that coincided temporally with a transition in peptide conformation from random coil to beta-sheet. Interestingly, this membrane activity was not mimicked with chemically equivalent A beta s that immediately adopted a beta-sheet conformation in water ('pre-aged'). These findings suggest that, under conditions that allow for a gradual transition of random coil A beta to beta-sheet structures, peptide conformation may be an important determinant of the toxic consequences of A beta-mediated membrane conductances.

Amyloid beta-Peptides↗

Role of the pericytes of intra-acinar pulmonary artery in the structural remodeling of pulmonary vessels.

Whether or not the pericytes exist in the intra-acinar pulmonary arteries and their normal structure and morphological changes during development of the structural remodeling of pulmonary vessels were observed using a pulmonary hypertension model in rats induced by monocrotaline injection. The results showed that the pericytes in the peripheral pulmonary vessels proliferated and transformed into smooth muscle cells during development of pulmonary hypertension, and at the same time, the pericytes could synthesize and secrete extracellular matrix including collagen, suggesting that the pericytes play an important role in the development of pulmonary hypertension and structural remodeling of the pulmonary vessels.

Animals↗