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F F Liu

Publications and source records attributed to F F Liu.

At least 19 recordsLinked to original sources
PubMed2001

The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region.

PURPOSE: Ipsilateral techniques designed to restrict treatment to the primary tumor and neck on the same side have been used in selected cases of cases of carcinoma of the tonsillar region at our institution for many years. The primary purpose of this study is to evaluate the risk of failure in the opposite neck in cases selected for unilateral radiotherapy over a 21-year period. METHODS AND MATERIALS: Ipsilateral radiotherapy techniques were used in 228 of 642 patients with carcinoma of the tonsillar region from 1970 to 1991. Local control, regional lymph-node control (including contralateral failure), and survival were calculated for different degrees of tumor extent treated with these techniques. RESULTS: Mean follow-up was 7 years. Cases tended to be T1 and T2, with N0 disease. The 3-year actuarial local control rate was 77% and cause-specific survival was 76%. Opposite neck failure was seen in 8 patients (crude rate of 3.5%). In the earlier period of the study, primary coverage was problematic in a proportion of cases and resulted in higher rates of local failure. CONCLUSION: Appropriately selected cases of carcinoma of the tonsil show minimal risk of failure in the opposite neck with ipsilateral techniques. Patients should undergo computed tomography planning to ensure adequate target coverage.

Adult↗
PubMed2001

A comparison of published head and neck stage groupings in carcinomas of the tonsillar region.

BACKGROUND: The combination of T, N, and M classifications into stage groupings was designed to facilitate a number of activities including: the estimation of prognosis and the comparison of therapeutic interventions among similar groups of cases. The authors tested the UICC/AJCC 5th edition stage grouping and seven other TNM-based groupings proposed for head and neck cancer to determine their ability to meet these expectations in a specific site: carcinoma of the tonsillar region. METHODS: The authors defined four criteria to assess each stage grouping scheme: 1) The subgroups defined by T and N comprising a given group within a grouping scheme have similar survival rates (hazard consistency); 2) The survival rates differ across the groups (hazard discrimination); 3) The prediction of cure is high (outcome prediction); and 4) The distribution of patients among the groups is balanced. The authors identified or derived a measure for each criterion and the findings were summarized using a scoring system. The range of scores was from 0 (best) to 7 (worst). Data were from a retrospective chart review on 642 cases of carcinoma of the tonsillar region treated with radiotherapy for cure at the Princess Margaret Hospital from 1970-1991. None of the patients had distant metastases. RESULTS: The scheme proposed by Synderman and Wagner, which was published in Otolaryngology Head and Neck Surgery in 1995 (vol.112, pages 691-4), scored best at 1.2. The UICC/AJCC scheme scored worst at 6.1. The hazard consistency ranged from a 3.1% average survival difference to 6.7% across the 8 schemes. The hazard discrimination measure varied by 28% from the best to worst scheme. Prediction varied by up to almost twofold across the schemes assessed. The distribution of patients varied from expected by between 0.13% and 0.57%. CONCLUSION: UICC/AJCC stage groupings were defined without empirical investigation. When tested, this scheme did not perform as well as any of seven empirically-derived schemes the authors evaluated. The results of the current study suggest that the usefulness of the TNM system can be enhanced by optimizing the design of stage groupings through empirical investigation.

Carcinoma, Squamous Cell↗
PubMed2001

The role of protein kinase B (PKB) in modulating heat sensitivity in a human breast cancer cell line.

PURPOSE: Protein kinase B (PKB) is a critical mediator of phosphoinositide 3-kinase-dependent survival signals in mammalian cells. Its activity is induced after heat shock, and is inhibited in cells undergoing apoptosis. We hypothesized that PKB may be an important modulator for heat-induced apoptosis in human cancer cells. METHODS AND MATERIALS: MCF-7 cells were transfected using four different plasmids, encoding a kinase-dead mutant PKB-AAA, a constitutively activated mutant PKB-DD, wild-type PKB, and the neomycin-resistant selection gene. These stable transfectants were subjected to heat shock, and assessed for PKB phosphorylation, PKB activity, and likelihood of undergoing apoptosis. RESULTS: After heating to 45 degrees C x 30 mins, 25% of MCF-7/neo transfectants underwent apoptosis, which increased to 38% in the presence of wortmannin (WT), an inhibitor of phosphoinositide 3-kinase. In contrast, 23% of the constitutively activated MCF-7/DD transfectants underwent apoptosis, minimally affected by WT. Heat-induced apoptosis occurred in 34% of the kinase-dead MCF-7/AAA transfectants, which increased further to 58% with the addition of WT. This in turn was associated with a two-fold reduction in clonogenic survival compared to the MCF-7/neo transfectants. CONCLUSION: Heat shock activation of PKB in human MCF-7 cells appears to be a significant modulator of heat-induced apoptosis and survival. Further understanding of this important pathway may offer potential in developing novel strategies in cancer therapy.

Apoptosis↗
PubMed2001

Carcinoma-in-situ of the glottic larynx: results of treatment with radiation therapy.

PURPOSE: Carcinoma-in-situ (CIS) of the vocal cords frequently progresses to invasive disease if untreated. Treatment approaches include vocal cord stripping, radiation therapy (RT), and laser excision. The purpose of this analysis was to assess the efficacy and safety of a standard RT regimen in the treatment of this condition. METHODS AND MATERIALS: Between January 1980 and December 1994, 67 patients (52 men, 15 women; median age, 65 years) with glottic CIS were treated with RT. The standard RT regimen was 51 Gy in 20 fractions given over 4 weeks (99% of patients). Prior to receiving RT, 21 patients (31%) had undergone 1 or 2 vocal cord stripping procedures, and 1 had been treated with laser. RESULTS: With a median follow-up of 6.5 years, 1 patient developed invasive glottic cancer, giving a 5-year actuarial local control rate of 98%. This patient recurred 14 months after treatment and was salvaged with laryngectomy. He is currently free of disease 2 years after surgery. There were no serious acute or late treatment complications. Sixteen patients (24%) developed subsequent malignancies, 8 of these being in the upper aerodigestive tract, although none were in the radiation field. CONCLUSIONS: Moderate-dose radiation therapy is an effective treatment for glottic CIS. It is well tolerated, produces no serious acute or long-term side effects, with an excellent cure rate.

Adult↗
PubMed2001

Potential molecular prognostic markers in head and neck squamous cell carcinomas.

BACKGROUND: Current management strategies for squamous cell carcinoma of the head and neck (HNSCC) rely on an understanding of the natural history of the disease, along with the use of prognostic factors to guide selection of appropriate treatment. However, it is recognized that tumor heterogeneity limits the reliable use of currently available prognostic markers. With the evolving understanding of the genetic and molecular basis of human malignancies, there has been much interest in determining whether specific molecular changes in HNSCC might guide treatment decisions. METHODS: A literature review of potential molecular markers relevant to HNSCC was undertaken and evaluated. It is evident that the published information is promising but, oftentimes, limited by a scarcity of large, uniformly staged and treated patients, from which the value of novel molecular markers can be assessed. RESULTS: On the basis of the review of more than 100 articles, some of the emerging molecular markers that might provide independent prognostic information include epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha), cyclin D1, and p53. This review will discuss the current status of these molecular factors and consequent implications for novel therapeutic approaches for patients with HNSCC. CONCLUSION: With the evolving understanding that human malignancies have developed and progressed on the basis of accumulated molecular abnormalities, there is an existing body of work trying to determine whether such abnormalities can predict clinical behavior of HNSCC. Such studies have to be conducted rigorously to derive useful information. Nevertheless, the role of such molecular markers, and the possibility to exploit them for therapeutic gain, is already at the horizon.

Biomarkers, Tumor↗
PubMed2001

Adenovirus-p53 gene therapy in human nasopharyngeal carcinoma xenografts.

BACKGROUND: One major challenge to human cancer gene therapy, is efficient delivery of the gene-vector complex. METHODS AND RESULTS: Using two distinct human nasopharyngeal carcinoma (NPC) models, we demonstrate that intra-tumoural (IT) administration of adenoviral-mediated wild-type p53 gene therapy (Ad-p53) caused no greater inhibition of tumour growth as compared to ionizing radiation (XRT) alone. Detailed histologic examination of tumour sections demonstrated that <15% of tumour cells were transduced by IT adv-beta-gal. CONCLUSIONS: This report underscores the importance of developing gene transfer vectors, which can provide therapeutic levels of transgene expression efficiently in solid tumours.

Adenoviridae↗
PubMed2001

Cisplatin chemotherapy plus adenoviral p53 gene therapy in EBV-positive and -negative nasopharyngeal carcinoma.

We have previously shown that the introduction of human recombinant wild-type p53 mediated by an adenoviral vector (Ad5CMV-p53), either alone or delivered in combination with ionizing radiation, was cytotoxic to two nasopharyngeal carcinoma (NPC) cell lines. To further explore the potential therapeutic role for gene therapy, the combination of Ad5CMV-p53 and cisplatin was examined in two NPC cell lines, CNE-1 and C666-1. The C666-1 cells are particularly relevant because they express Epstein-Barr virus latent gene products analogous to human NPC in situ. Cells were infected with 5 pfu/cell of Ad5CMV-p53 or Ad5CMV-beta-gal, followed by exposure to increasing doses of cisplatin. Clonogenic and MTT assays were used to assess the sensitivity of cells to these treatments, and apoptosis was also quantified. The combination of Ad5CMV-p53 and cisplatin resulted in approximately 25% greater cytotoxicity compared to that observed with cisplatin alone in either cell line. Apoptosis was induced in approximately 50% of cells following administration of both Ad5CMV-p53 and cisplatin, but was induced in considerably fewer cells following either treatment alone. The two modalities appeared to interact in an additive manner. Ad5CMV-p53 gene therapy resulted in the expression of biologically active p53 protein, shown by induction of p21(WAF1/CIP1). Cisplatin treatment showed little effect on either p53 or p21(WAF1/CIP1) expression. Therefore, both p53 gene therapy and cisplatin chemotherapy demonstrated cytotoxicity mediated by apoptosis despite the presence of EBV gene products in the C666-1 cells, but it appears that the two modalities induce cytotoxicity by independent pathways.

Adenoviridae↗
PubMed2001

Outcome of curative management of malignant tumours of the parotid gland.

PURPOSE: The optimal management of malignant parotid gland tumours remains to be defined precisely. Specifically, a further understanding of the tumour features that influence treatment outcome is needed. MATERIALS AND METHODS: A retrospective review was conducted on 184 patients who were registered at the Princess Margaret Hospital with a diagnosis of a primary malignant parotid gland tumour. RESULTS: All patients were initially managed with a parotidectomy, and postoperative x-ray radiation therapy (XRT) was administered to 159 patients. The actuarial 5-year cause-specific survival and locoregional control rates were 76% and 81%, respectively. The survival and locoregional control rates for patients treated with surgery alone versus surgery plus postoperative XRT were not statistically different. A multiple regression analysis identified only age and tumour category to be independently significant prognostic factors for both survival and locoregional control. CONCLUSION: We would recommend that patients with malignant parotid gland tumours be managed with parotidectomy, followed by postoperative XRT for tumours with residual disease, aggressive histology, and/or positive lymph nodes.

Adolescent↗
PubMed2001

[Application of wide-bore capillary gas chromatography in the synthesis of special esters of methacrylic acid].

A simple, rapid and accurate method for separating and analysing components in the synthesis of special esters of methacrylic acid by gas chromatography is reported. An SE-54 wide-bore capillary column of 50 m x 0.53 mm i.d. x 0.6 microns was used. The esters include dimethylaminoethyl methacrylate(DMAM), n-butyl methacrylate(BMA) and ethylene glycol dimethacrylate(EGDMA). Crude materials such as methyl methacrylate(MMA) and N, N-dimethyl ethanol amine (DMEA) were also analysed. The recoveries were 99.71%-102.89%, and the RSDs of the main components were below 0.1%. The method can be used to control the production of the esters.

English Abstract↗
PubMed2000

Evaluation of major active components in St. John's Wort dietary supplements by high-performance liquid chromatography with photodiode array detection and electrospray mass spectrometric confirmation.

A RP-HPLC method with photodiode array detection and LC-electrospray ionization (ESI) MS confirmation was established for the determination of major active components in St. John's Wort dietary supplement capsules. The samples alternatively were extracted with ethanol-acetone (2:3) using a 55 degrees C water-bath shaker or an ambient temperature ultrasonic bath. Extracts were separated by RP-C18 chromatography using a 95-min water-methanol-acetonitrile-trifluoroacetic acid gradient. The major components were identified by photodiode array detection and then confirmed by LC-ESI-MS. The quantification of components was performed using an internal standard (luteolin). This method may serve as a valuable tool for the quality evaluation of St. John's Wort dietary supplement products.

Calibration↗
PubMed2000

A phase II study of Biotene in the treatment of postradiation xerostomia in patients with head and neck cancer.

One of the major side effects of radical radiation therapy for head and neck malignancies is xerostomia, or dryness of the mouth. There is no clearly effective treatment for this condition, but we have observed that patients in our practice believe that their symptoms improve significantly when using two "over-the-counter" oral comfort products - Biotene (toothpaste, mouthwash and chewing gum) and Oralbalance gel. We decided to study these agents in a formal phase II study to evaluate their usefulness in patients with postirradiation xerostomia. Twenty-eight patients with post-irradiation xerostomia were entered on the study. All had biopsy-proven carcinoma of the nasopharynx, oropharynx, oral cavity, hypopharynx or larynx, and had received primary radiotherapy with curative intent (> or =50 Gy in 20 fractions) more than 4 months before study entry. More than 75% of both parotid glands were included in the primary radiation field. There was no clinical evidence of recurrent disease. Patients were provided with a 2-month supply of Biotene mouthwash, toothpaste, chewing gum and Oralbalance gel. Response was evaluated 1 and 2 months after study entry using a patient-completed visual analogue scale to assess the severity of xerostomia and its effects on quality of life. For analysis, the scored baseline was subtracted from the later scores to assess change. Patients with an increase of 10 mm from their baseline score on the visual analogue scale were classified as having responded to the treatment intervention, and those with an increase of > or =25 mm from their baseline score were classified as having experienced a major improvement in their symptoms. After 2 months of treatment, 15 patients (54%) reported an improvement in intraoral dryness and 10 of these patients (36%) reported a major improvement. Similar proportions of patients (46% some improvement, 25% major improvement) reported an improvement in their ability to eat normally. Seventeen patients (61%) reported an improvement in oral discomfort, and 12 of these (43%) had a major improvement in their symptoms. The results of this study suggest that the use of Biotene (mouthwash, toothpaste and chewing gum) and Oralbalance gel can improve many of the symptoms of radiation-induced xerostomia. A placebo effect could account for many of the observed improvements in symptoms, and in order to assess the role of these agents in the management of patients with postirradiation xerostomia a randomised phase III study is needed.

Administration, Oral↗
PubMed2000

Carcinoma of the maxillary antrum: a retrospective analysis of 110 cases.

BACKGROUND AND PURPOSE: Cancer of the maxillary antrum is a rare disease with a variety of treatment options. The present study was undertaken to review the outcome of patients with carcinoma of the maxillary antrum managed at a single institution. MATERIALS AND METHODS: A retrospective analysis of 110 cases of carcinoma of the maxillary antrum managed with curative intent during the time period 1976-1993 was performed. There were 33 females and 77 males; the median age was 64 years (range 38-89). The median follow-up time was 4 years (range from 2 months to 17 years). The majority of patients presented with locally advanced disease (78 T4 tumours); nodal involvement was observed in 17/110 cases. Histologic subtypes included in the analysis were limited to squamous cell carcinoma (95 cases) and undifferentiated carcinoma (15 cases). Patients were managed with either primary radiation therapy with surgery reserved for salvage (83/110) or with a planned combined approach with surgery and either pre or postoperative radiation (27/110). RESULTS: The actuarial 5-year cause-specific survival rate was 43%. The 5-year local control rate was 42%. Of 63 patients with local failure, 25 underwent salvage surgery with a subsequent 5-year cause-specific survival of 31%. Multiple regression analysis of patient, disease and treatment related variables identified local disease extent and nodal disease at presentation as the only variables independently associated with cause-specific survival. CONCLUSIONS: This analysis indicates that survival from carcinoma of the maxillary antrum is poor with outcome strongly related to local disease extent. The best treatment strategy for this disease remains undefined. Salvage surgery can result in prolonged survival in selected patients experiencing local failure.

Adult↗
PubMed2000

Liquid chromatographic analysis of incurred amoxicillin residues in catfish muscle following oral administration of the drug.

Improper application of antibiotic chemicals to livestock and aquaculture species may lead to the occurrence of residues in food supplies. An appropriate depletion period is needed after the administration of drugs to animals for ensuring that residues in edible tissues are below established tolerance levels. This study was conducted to determine incurred amoxicillin residues in catfish muscle following oral administration. Dosed fish were harvested after four depletion periods, and muscle fillets were analyzed for amoxicillin residues using an HPLC method with precolumn derivatization and fluorescence detection. The residue levels in fish after a 6-h depletion ranged from 40 to 64 ng/g with one exception at 297 ng/g. Average residue levels decreased to 5.4 and 2. 8 ng/g after 24- and 48-h depletions, respectively. Residue levels after a 72-h depletion decreased to below the method's limit of quantitation (1.2 ng/g). An LC-MS/MS confirmatory method was developed. Confirmation of the presence of amoxicillin was demonstrated in incurred fish samples containing residues at approximately 50-300 ng/g.

Administration, Oral↗
PubMed2000

Optimization of extraction conditions for active components in Hypericum perforatum using response surface methodology.

Optimal conditions for extraction of Hypericum perforatum were determined using response surface methodology. A 3 x 4 x 4 full factorial design representing three extraction temperatures, four extraction times, and four solvent concentrations was executed. The overall extraction efficiency was defined by comparing either the total extractable material weight or the individual component peak area to the peak area of luteolin as internal standard. Of the tested variables, the extraction temperature most significantly affected extraction efficiency. Higher temperatures gave better extraction efficiencies, but high temperature also caused decomposition of hypericin. Within the test range, responses for most variables had local maxima. Optimum ranges of time and concentration for individual variables were overlaid. Considering all variables, optimum ranges for extraction time and extraction solvent concentration (percent ethanol in acetone) were 5.0-6.7 h and 44-74% at 23 degrees C, 5.4-6.9 h and 45-72% at 40 degrees C, and 5.3-5.9 h and 44-69% ethanol in acetone at 55 degrees C, respectively.

Hypericum↗
PubMed2000

Heat-directed gene targeting of adenoviral vectors to tumor cells.

Targeting therapeutic gene expression to tumor cells represents a major challenge for cancer gene therapy. The strong transcriptional response exhibited by heat shock genes, along with the beneficial therapeutic effects of hyperthermia have led us to develop a heat-directed gene-targeting strategy for cancer treatment. Heat shock gene expression is mediated in large part by the interaction of heat shock factor 1 with specific binding sites (heat shock elements; HSE) found in the promoters of heat-inducible genes. Here we present a quantitative analysis of heat-inducible gene expression mediated by the wild-type hsp70b gene promoter, as well as a modified hsp70b promoter containing additional HSE sequences. Beta-galactosidase (beta-gal) expression was induced between 50- and 800-fold in a panel of human breast cancer cell lines infected with an adenoviral vector containing the wild-type hsp70b promoter (Ad.70b.betag) following treatment at 43 degrees C for 30 minutes. Infection with an adenoviral vector containing the modified hsp70b promoter (Ad.HSE.70b.betag) resulted in a 200- to 950-fold increase in beta-gal expression under the same conditions, and also provided a 1-2 degrees C decrease in the threshold of activation. Significant increases in the heat responsiveness of the Ad.HSE.70b.betag construct were observed in five of six tumor cell lines tested, as well as under thermotolerant conditions. Finally, we demonstrate that localized heating of a HeLa cell xenograft can effectively target beta-gal gene expression following intratumoral injection of Ad.70b.betag. Adenoviral vectors incorporating heat-inducible therapeutic genes may provide useful adjuncts for clinical hyperthermia.

Adenoviridae↗
PubMed1999

The effects of combining ionizing radiation and adenoviral p53 therapy in nasopharyngeal carcinoma.

PURPOSE: Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region, with a 5-year survival level of approximately 65%. To explore gene therapy as a novel approach which might improve outcome, we have shown previously that introduction of human recombinant wild-type p53 mediated by the adenoviral vector (Ad5CMV-p53) was cytotoxic in two human nasopharyngeal carcinoma (NPC) cell lines (CNE-1 and CNE-2Z). The current work was designed to determine whether this strategy, combined with ionizing radiation (XRT), was more effective than either treatment alone. METHODS AND MATERIALS: CNE-1, CNE-2Z, and a normal human nasopharyngeal fibroblast strain, KS1, were infected with 2- and 6-plaque-forming units (pfu)/cell of Ad5CMV-p53, respectively. These doses were isoeffective for beta-galactosidase activity in the CNE-1 and CNE-2Z cells. XRT was administered 24 h post-infection, and Western blot analyses were conducted for p53, p21WAF1/CIP1, bax, and bcl-2 2 days after XRT. Cell survival was assessed using a clonogenic assay. Presence of DNA ladders reflecting apoptosis was detected using DNA agarose gel electrophoresis, and cell cycle was analyzed using flow cytometry. RESULTS: The combination of Ad5CMV-p53 plus XRT (2, 4, and 6 Gy) resulted in an approximately 1-log greater level of cytotoxicity compared to that observed with XRT alone for both NPC cell lines. The two modalities appear to be interacting in a synergistic manner in cancer cells, but not in KS1 fibroblasts. XRT alone stimulated minimal p53 expression in control cells; Ad5CMV-p53 alone induced significant recombinant p53 expression, which was not further enhanced by the addition of XRT. Similar observations were made for p21WAF1/CIP1 expression. No changes were observed for bax or bcl-2 expression with any of these treatments. Apoptosis was induced following 4 Gy of XRT alone, but was observed after only 2 Gy when combined with Ad5CMV-p53. Cell cycle analysis indicated that Ad5CMV-p53 infection did not perturb the cell cycle beyond that observed with XRT alone. CONCLUSION: p53 gene therapy and XRT appears to interact in a synergistic manner; underscoring the significant potential of this novel strategy in the treatment of NPC.

Adenoviridae↗
PubMed1999

Inhibition of protein kinase C activity promotes heat-induced apoptosis in RIF-1 but not in TR-4 cells.

PURPOSE: Inhibition of protein kinase C (PKC) activity has been demonstrated to reduce thermotolerance (TT), presumably by decreasing heat shock protein (HSP) production. Therefore, the interest was in evaluating this relationship further in two isogenic murine tumour cell lines: RIF-1 and its thermoresistant TR-4 selectant. MATERIALS AND METHODS: TT was induced in RIF-1 and TR-4 cells (45 degrees C for 15 min, then 37 degrees C for 6 h) with or without Ro31-8220, a specific inhibitor of PKC. PKC activity was assayed by determining the catalytic transfer of ATP to a specific substrate peptide. Survival was determined using the clonogenic assay. Apoptosis was quantitated by counting the number of cells demonstrating apoptosis after staining with acridine-orange/ ethidium bromide. Production of the inducible form of HSP70 was assessed using Western blot. RESULTS: At 2 microM Ro31-8220, >80% of PKC activity was inhibited in both cell lines, which was associated with no cytotoxicity at 37 degrees C. Basal HSP70 level was approximately 10-fold higher in the TR-4 compared with the RIF-1 cells. Upon TT induction, HSP70 level increased significantly in both cell lines, which was suppressed in the presence of Ro31-8220, but the relative amount of HSP70 remained high in the TR-4 cells. At 24 h, heat-induced apoptosis increased from 4 to 38% in RIF-1 cells in the presence of Ro31-8220, which was associated with a 26% reduction in clonogenic survival after thermotolerant heating. In contrast, <1% of TR-4 cells demonstrated apoptosis even with the highest dose of Ro31-8220, and no effect on survival was observed. CONCLUSION: Inhibition of PKC activity reduces HSP70 induction, which in turn is associated with promotion of heat-induced apoptosis in RIF-1 cells. However, the survival signals in the TR-4 cells are so strong, that even 80% inhibition of PKC activity has minimal impact on heat-induced apoptosis and survival in this thermoresistant cell line.

Animals↗