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Biomedical subjects

P Hui

Publications and source records attributed to P Hui.

At least 19 recordsLinked to original sources
PubMed2007

A double-blind placebo-controlled randomized study of Chinese herbal medicine as complementary therapy for reduction of chemotherapy-induced toxicity.

BACKGROUND: Chinese herbal medicine (CHM) is a common complementary therapy used by patients with cancer for reduction of chemotherapy-induced toxic effects. This study applied the highest standard of clinical trial methodology to examine the role of CHM in reducing chemotherapy-induced toxicity, while maintaining a tailored approach to therapy. PATIENTS AND METHODS: Patients with early-stage breast or colon cancer who required postoperative adjuvant chemotherapy were eligible for the study. Enrolled patients were randomly assigned to one of three Chinese herbalists who evaluated and prescribed a combination of single-item packaged herbal extract granules. Patients received either CHM or placebo packages with a corresponding serial number. The placebo package contained nontherapeutic herbs with an artificial smell and taste similar to a typical herbal tea. The primary end points were hematologic and non-hematologic toxicity according to the National Cancer Institute Common Toxicity Criteria Version 2. RESULTS: One hundred and twenty patients were accrued at the time of premature study termination. Patient characteristics of the two groups were similar. The incidence of grade 3/4 anemia, leukopenia, neutropenia, and thrombocytopenia for the CHM and placebo groups were 5.4%, 47.3%, 52.7%, and 1.8% and 1.8%, 32.2%, 44.7%, and 3.6%, respectively (P = 0.27, 0.37, 0.63, and 0.13, respectively). Incidence of grade 2 nausea was the only non-hematologic toxicity that was significantly reduced in the CHM group (14.6% versus 35.7%, P = 0.04). CONCLUSIONS: Traditional CHM does not reduce the hematologic toxicity associated with chemotherapy. CHM, however, does have a significant impact on control of nausea.

Adult↗
PubMed2006

Quality of life is predictive of survival in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Patients with unresectable hepatocellular carcinoma (HCC) have a dismal prognosis. The objective of this study was to evaluate whether patient-reported baseline quality of life (QoL) measured by the EORTC QLQ-C30 instrument is predictive of survival for these patients. MATERIALS AND METHODS: Two hundred and thirty-three patients with unresectable HCC (mainly hepatitis B-associated) who were recruited into two separate randomized phase III clinical studies, based on palliative chemotherapy and palliative hormonal therapy, respectively, gave consent and received pretreatment QoL assessment. EORTC QLQ-C30 scores and clinical variables at the time of study entry were analyzed to identify factors that influenced survival by applying multivariate analysis. Independent prognostic factors for survival were studied by Cox regression analysis. RESULTS: Median survival of the 233 patients was 5.5 months (95% CI 4.2-6.5 months). Significant independent predictors of shorter survival were advanced Okuda staging (P = 0.0030; HR = 2.058), high baseline total bilirubin (P = 0.0008; HR = 1.013) and worse QoL score in the appetite score domain (P = 0.0028; HR for 10 point increase = 1.070). Patients who were entered into the chemotherapy trial (P = 0.0002; HR = 0.503), those who scored better in the physical functioning domain (P = 0.0034; HR for 10 point decrease = 0.911) and the role functioning domain (P = 0.0383; HR for 10 point decrease = 0.944) of the QoL questionnaire, were associated with longer survival. CONCLUSIONS: In the studied HCC population, patient-reported baseline QoL provides additional prognostic information that supplements traditional clinical factors, and is a new prognostic marker for survival for patients with unresectable HCC.

Adolescent↗
PubMed2004

Patients with uterine papillary serous cancers may benefit from adjuvant platinum-based chemoradiation.

OBJECTIVE: The coexistence of minimal uterine disease and extrauterine metastases is common in patients with uterine papillary serous carcinoma (UPSC). Only complete surgical staging accurately depicts the extent of this disease. The purpose of this study was to evaluate different therapeutic options in surgically staged patients. METHODS: We retrospectively reviewed all patients with UPSC histologically limited in the uterus to the endometrium treated at our institution between 1987 and 2002. RESULTS: Twenty-three (45%) cases were International Federation of Gynecology and Obstetrics (FIGO) stage IA, seven (15%) were stage IIIA, one (2%) was stage IIIC, and nine (18%) stage IV. Additionally, 11 of these 51 patients (21%) were diagnosed with two cancers: a stage IA UPSC and concomitant advanced stage serous cancer of the ovary, fallopian tube, or peritoneum. Stage IA patients with no cancer in the hysterectomy specimen (defined as no residual uterine disease) had no recurrences (n = 10) regardless of treatment. There was a trend toward increased survival in stage IA patients with residual uterine disease who were treated with chemoradiation (concomitant vaginal brachytherapy and platinum-based chemotherapy). There were no recurrences in patients with locoregional disease (stages IA-IIIA) who received chemoradiation. All patients with advanced stage UPSC (stage IIIC or IV or two primary cancers) did poorly regardless of treatment. CONCLUSION: Our findings suggest that stage IA patients with no residual uterine disease may be observed. Stage IA patients with residual uterine disease may benefit from chemoradiation. More effective treatment needs to be identified for advanced stage UPSC.

Aged↗
PubMed2001

Towards developing a non-SnCl2 formulation for RP444, a new radiopharmaceutical for thrombus imaging.

There are many factors influencing the yield and radiochemical purity (RCP) of the radiopharmaceutical RP444. These include heating temperature, heating time, pH, the use of a buffering agent and a bulking agent, as well as the component (XV066, tricine, TPPTS, and Na99mTcO4) concentration. Through a series of radiolabeling experiments, we found that a formulation comprised of 20 microg of XV066, 6.5 mg of tricine, 40 mg of mannitol, 5 mg of TPPTS, and 0.1 mg of Pluronic acid dissolved in 1.0 mL of 250 mM succinate buffer (pH 5.0) gives the best RCP for RP444. The formulation can be lyophilized to form a stable crystal "cake". The radiolabeling is achieved by adding 1.5 mL generator eluant (33-133 mCi of Na99mTcO4) to a lyophilized vial and heating the reaction mixture at 100 degrees C for 10 min. Using this formulation, RP444 is prepared consistently in high yield with RCP > or = 90%. Formation of [99mTc]colloid is minimal (< 0.5%).

Chromatography, High Pressure Liquid↗
PubMed2001

Assessment of clonality in melanocytic nevi.

BACKGROUND: Melanocytic nevi are among the most common lesions in man; however; their pathogenesis remains largely unknown. While often held to be neoplastic, this hypothesis has not been conclusively verified. Alternatively, some authorities have held that melanocytic nevi are hamartomas. More practically, difficulty may be encountered in the histologic discrimination of melanocytic nevi from melanoma. It was reported that nevi may be differentiated from melanoma in females by polymerase chain reaction (PCR) analysis of loci of human androgen receptor gene on the X-chromosome. However, contradictory findings have also been reported, suggesting that both acquired nevi and melanoma are clonal. METHODS: Fifteen examples of melanocytic nevus were analyzed via PCR for pattern of X-chromosome inactivation as indicated by the methylation status of the human androgen receptor gene. RESULTS: Among 15 nevi analyzed, 11 cases provided informative polymorphism at the androgen receptor loci. Nine of these 11 cases revealed a non-random pattern of X-chromosome inactivation. CONCLUSIONS: These findings suggest that melanocytic nevi are clonal/neoplastic lesions. As such, they cannot be discriminated from melanoma on the basis of clonality.

Clone Cells↗
PubMed2001

Intraplacental smooth muscle tumor: a case report.

We present the second reported case of a smooth muscle neoplasm involving the placental parenchyma. On gross examination, the tumor easily separated from the uterus and had a whorled cut surface with finger-like extensions into the villous parenchyma, very similar to the previously described case. The differential diagnosis included a primary smooth muscle tumor of the placenta (placental leiomyoma), a primary uterine neoplasm incorporated into the placenta, and a metastatic sarcoma. In this case, the infant was male, and the polymerase chain reaction technique demonstrated the presence of Y chromosome gene in the placental parenchyma and its absence in the placental neoplasm. Thus, this neoplasm, despite its gross appearance of a primary placental tumor, actually represented an incorporated benign uterine leiomyoma.

Adult↗
PubMed2001

Gross elevation of TT virus genome load in the peripheral blood mononuclear cells of cancer patients.

TT virus (TTV) is a recently described circular DNA virus of about 3.8 kb, which is related to the circoviridae viruses. It is commonly detected in healthy subjects and no association with any specific disease has been established. TTV was initially thought to be hepatotropic, but subsequent reports have shown that it is detectable in other tissues, including kidney, prostate, mammary gland, brain, bone marrow, and peripheral blood mononuclear cells. Plasma samples from cancer patients and healthy subjects were tested for the presence or absence of TTV by heminested polymerase chain reaction (PCR). We also developed a quantitative competitive PCR (QC-PCR) assay for TTV that permits accurate measurement of TTV DNA load. Using this assay, the TTV genome load in peripheral blood mononuclear cells (PBMCs) of healthy control subjects (n = 50) and patients with various types of cancer (n = 148), including breast cancer, non-Hodgkin's lymphoma, colon cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and other cancers, was measured. TTV DNA was detected in 69 of 100 plasma samples (69%) of cancer patients tested and in 39 of 100 plasma samples (39%) randomly selected from 1000 plasma samples of blood donors (p < 0.05). TTV DNA was detectable in the PBMCs of 99% of the cancer patients and 86% of the controls. However, the median virus load was more than 100-fold higher in the cancer patients (3599 copies/100,000 cells) than among the controls (30 copies/100,000 cells; p < 0.0001). There was no significant difference in TTV load among the different cancer types. Using a cutoff value of >250 copies per 100,000 PBMCs, 93.2% of cancer patients were "positive" compared to only 4% of healthy control subjects. Almost all the cancer patients have TTV infection and their TTV genome load in PBMCs is significantly higher than that in control subjects. It remains to be elucidated whether such findings are specific to cancer patients or occur in all seriously ill subjects.

Adult↗
PubMed2000

Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors.

Hepatitis B virus (HBV) reactivation is a well-described complication in cancer patients who receive cytotoxic chemotherapy and may result in varying degrees of liver damage. As chemotherapy is used increasingly in cancer patients, HBV reactivation during cytotoxic treatment may become a more common problem. In lymphoma patients, the incidence of chronic HBV infection has been reported to be 26%, of whom 47% developed HBV reactivation during chemotherapy. However, corresponding data for patients with other malignancies undergoing cytotoxic chemotherapy are not known. In this prospective study, hepatitis B surface antigen (HBsAg) was determined in 626 consecutive cancer patients who received cytotoxic chemotherapy over a 12-month period. Seventy-eight patients (12%) were found to be HBsAg positive. Thirty-four (44%) developed raised alanine transaminase during their course of chemotherapy. In these 34 patients, hepatitis was attributed to HBV reactivation in 15 patients (44%), chronic active HBV infection in 1 patient (3%), hepatitis C infection in 1 patient (3%), malignant hepatic infiltration in 2 patients (6%), and the use of hepatotoxic chemotherapeutic agents in 11 patients (32%). The causes of hepatitis were unknown in 4 patients (12%). HBV reactivation was more likely to develop in patients who were male, younger age, HBeAg seropositive, and those with lymphoma. Presence of malignant hepatic infiltration, baseline pre-treatment alanine transaminase, total bilirubin, and HBV DNA levels did not correlate with the development of HBV reactivation. Of the 15 patients who developed HBV reactivation, antiviral therapy with lamivudine was available and used in 9. There was no HBV-related mortality during chemotherapy. It is concluded that in patients with chronic HBV infection under chemotherapy, HBV reactivation occurs in nearly 20% of them and accounts for 44% of hepatitis cases. The risk factors identified include male sex, younger age, HBeAg seropositive, and the diagnosis of lymphoma. In HBV endemic areas, patients with risk factors for HBV reactivation should be identified prior to receiving cytotoxic treatment and monitored closely. The potential benefit of lamivudine requires further confirmation.

Adult↗
PubMed2000

Pathogenesis of placental site trophoblastic tumor may require the presence of a paternally derived X chromosome.

Placental site trophoblastic tumor (PSTT) is a neoplastic proliferation of intermediate trophoblasts that invades the myometrium at the placental site after a pregnancy. Less than 100 cases have been reported. Information of the sex assignment of the antecedent gestation is available in 21 cases: 18 of these were female. To explore this interesting phenomenon, we have determined the sex chromosome composition of the tumor tissue preserved in paraffin blocks for five new cases of this condition. The last documented gestational event included a normal vaginal delivery of female infants in three cases, normal vaginal delivery of an infant of unknown sex in one case and a molar gestation in one case. Using the X-linked human androgen receptor (AR) gene as a polymorphic marker, we showed that in all five cases the tumor had a likely XX chromosomal composition; and in four cases it was possible to determine that one of the X chromosomes was of paternal origin. In one case, the paternal X chromosome showed no polymorphism to either maternal X chromosomes. In addition, sensitive semi-nested PCR failed to show a human Y chromosome element in any of the five cases of PSTT. Overall, of 21 cases from the literature and 5 cases of ours, 89% (23 of 26) showed an XX genomic composition in PSTT, either by history or genetic analysis. These results suggest that most PSTT were derived from the antecedent female conceptus and were likely to have possessed a functional paternal X chromosome. Methylation status analysis at the AR locus was performed in the three PSTT in which the paternal X chromosome was identifiable. In two cases, the paternal AR locus was hypomethylated while the corresponding maternal locus was hypermethylated. The methylation status of other loci was not investigated. Collectively, sex chromosome analysis of five cases of PSTT with literature support suggests a unique genetic basis for the development of PSTT that involves the paternal X chromosome. Although largely speculative, an active paternal X chromosome may be of importance in the pathogenesis of PSTT.

Adult↗
PubMed2000

[Effect of mouse p53 minigene on lung cancer cells with different 172 structures regulated by tetracycline].

OBJECTIVE: To investigate the effect of mouse 172 wild-type p53 (Arg), pseudo-wild-mutant-type p53 (Arg-->Leu) and mutant-type p53 (Arg-->His) induced by absence of tetracycline on the growth of PG cell line. METHODS: Three variant types of p53 minigene were sub-cloned by gene recombination into an expression vector which was controlled by tetracycline. Through LipofectAMINE, the vectors were transfected into p53 defective PG (248CGG-->CTT) cells, and the transfectants were screened in the selecting medium containing puromycin. Tumor suppressing effects were studied by MTT absorption, flow cytometry and Western blotting. RESULTS: Wild-type p53 and pseudo-wild-mutant-type p53 could lead cells to decrease their growth rates, arrest cell cycle and transactivation of p21(WAF1). Mutant-type p53 was defective in tumor suppression. CONCLUSION: Wild-type p53 and pseudo-wild-type p53 may inhibit cell growth and induce cell cycle arrest. Some p53 variants such as 172 Arg-->Leu can still retain the tumor suppression function of the wild-type.

Amino Acid Substitution↗
PubMed1999

Primary nasal and nasopharyngeal lymphomas: a comparative study of clinical presentation and treatment outcome.

Primary nasal lymphoma (NSL) and nasopharyngeal lymphoma (NPL) are uncommon extranodal lymphomas that have often been grouped together in studies published in the literature. It is unclear whether or not NSL and NPL are biologically different entities. We reviewed the records of 25 NSL and 19 NPL patients who were managed between 1985 and 1995, to evaluate and compare their clinical characteristics and treatment outcome. Clinical variables, including age, sex, stage, tumour bulk and treatment modality, were assessed for their prognostic influence on survival. Nasal obstruction (80%), nasal discharge (64%) and epistaxis (60%) were the predominant symptoms in NSL patients; neck swelling/mass (42%), nasal obstruction (37%) and hearing impairment (32%) were common findings in NPL patients. Limited stage disease (I/II) was present in all NSL and in 80% of the NPL patients. Thirty-six per cent of the NSL and 32% of the NPL patients had bulky disease. The majority of the immunophenotyped NSLs were of T-cell lineage (75%, 12/16) and most immunophenotyped NPLs were of B-cell lineage (69%, 11/16). The patients were treated with radiotherapy alone (14%), chemotherapy alone (23%) or chemotherapy plus radiotherapy (64%). NSL patients showed a lower complete remission rate and higher relapse rate than NPL patients, although the difference did not reach statistical significance. Both the 5-year disease-free survival (36% versus 76%; P = 0.007) and overall survival (33% versus 82%; P = 0.003) were significantly worse in NSL compared with NPL patients. Advanced age (>60 years; P = 0.03) and bulky disease (P = 0.04) were also associated with inferior survival times. The analysis of sex, stage and type of therapy showed no evidence of significant impact on the survival. Despite the close anatomical relationship in origin, NSL and NPL were noted to behave as biologically distinct entities, in which the NSLs demonstrated a higher frequency of T-cell tumours and a much worse prognosis than NPL. In addition to the primary site, advanced age and bulky disease were also associated with reduced survival.

Adult↗
PubMed1999

[Specific point-mutate p53 mini-gene transfectimg effects on biological behaviors of a human cancer cell line PG derived from human pulmonary giant carcinoma].

OBJECTIVES: To explore the suppressive effects of a murine genomic p53 minigene containing an Arg-->Leu substitution at its encoding amino acid 172 on biological behaviors of human carcinoma cell and evaluate its potential application in cancer gene therapy. METHODS: By LipofectaMINE and electraporation methods, this mutant p53 gene which lacked of exon 1 and intron 1 expression vector driven by CMV promoter was co-transfected with PCMVneo into PG cell in which dominant negative p53 pre-exists. A wild-type and another kind of genomic mutate-type p53 gene expression vector were transfected. The latter p53 gene encoding protein contained an Arg-->His substitution at the same position, and pBLuscript plasmid was used as control. All transfectants were screened by 500 micrograms/ml geneticin and identified by mouse specific p53 mRNA RT-PCR and Northern blot analysis. After transfection, the biological behavior changes were studied by colony formation and TUNEL test together with in-situ clone regression for chemosensitivity of anti-cancer drugs. RESULTS: The transfecting effects of this unusual p53 gene were surprisingly strong. They were more significant than those of the wild-type p53 and could suppress the formation of transgenic colonies and passage. The transgenic colonies were sensitive to be treated in adromycin and 5-Fu, and the gene transient expression could result in cell apoptosis. CONCLUSION: Codon 172 mutant (Arg-->Leu) p53 genomic DNA exhibited a strong suppressive transfecting effects on carcinoma cell, so it is a possible candidate to be used in cancer gene therapy.

Apoptosis↗
PubMed1998

Identification of candidate target genes for EVI-1, a zinc finger oncoprotein, using a novel selection strategy.

We have sought to identify and isolate target genes for the zinc finger protein, EVI-1, which has been implicated in the genesis of myelogenous leukemia both in mouse and human. We have approached this with a two-step selection: we first selected for genomic fragments of mouse DNA that bind to the protein with high affinity; second, we employed cDNA hybrid selection to identify gene sequences contained within these fragments. We show that we have constructed a sublibrary of genomic fragments that contains a significant fraction of the EVI-1-binding sites in the mouse genome. Our data has allowed us to estimate that there are approximately 4300 binding sites per haploid genome in the mouse. We further demonstrate that by using cDNA hybrid selection, it is relatively straightforward to isolate cDNAs that correspond to genes embedded in the EVI-1-binding sublibrary. Several of these are novel, but are represented in databases of anonymous human or mouse cDNAs (expressed sequence tags). One selected gene is Itpr2, encoding the inositol trisphosphate type two receptor, which is transcriptionally regulated during myelopoiesis. Finally, using a chimeric EVI-1-VP16-fusion protein under the control of a tetracycline-regulated system, we have shown that this chimeric activator can directly regulate Itpr2.

3T3 Cells↗
PubMed1998

Application of the international prognostic index in a study of Chinese patients with non-Hodgkin's lymphoma and a high incidence of primary extranodal lymphoma.

BACKGROUND: Chemotherapy containing anthracycline is the standard initial treatment for aggressive non-Hodgkin's lymphoma (NHL), and the International Prognostic Index (IPI) is widely accepted as the standard tool for determining the prognosis of patients with this disease. However, the data on which the IPI was based primarily came from studies conducted in Western countries. It may not be directly applicable to Asian populations, in which the incidence of primary extranodal lymphoma (PENL) is known to be high. METHODS: The authors conducted a retrospective study of 218 patients with aggressive NHL who were treated with chemotherapy. They analyzed the distribution of stage and pathology, prognostic factors, toxicity, and treatment outcome. The IPI was then applied and its ability to identify distinct prognostic groups tested. RESULTS: Eighty-six patients (39.4%) had lymph node lymphoma (LNL) and 132 (60.6%) had primary extranodal lymphoma (defined as non-Hodgkin's lymphoma with primary presentation, bulk of disease, and histologic confirmation at an extranodal site). The most common primary extranodal sites were the stomach (22%) and Waldeyer's tonsillar ring (18.9%). The complete response rate of PENL patients to chemotherapy containing anthracycline was 52%, as compared with 64% of the LNL group. The 5-year survival rates for patients with LNL and PENL were 57.4% and 52.1%, respectively. The toxicity in the two patient groups was similar. Four of the prognostic factors in the IPI-age, serum LDH, performance status, and disease stage-predicted significantly different survival for PENL and LNL patients. However, the number of extranodal sites involved was not a significant predictive variable in PENL. CONCLUSIONS: The IPI was applicable to this Chinese population in which the incidence of PENL was high, although the number of extranodal sites did not achieve statistical significance as a risk factor. A proposal for modification was made. Chemotherapy containing anthracycline was an effective treatment for both PENL and LNL patients.

Adolescent↗
PubMed1995

Isolation and functional characterization of the human gene encoding the myeloid zinc finger protein MZF-1.

The expression of the human myeloid zinc finger gene (MZF-1) by human bone marrow cells is necessary for granulopoiesis. We have analyzed the structure and function of the MZF-1 gene by diagnostic polymerase chain reaction, genomic cloning, and promoter analysis. Comparison of human promyelocytic HL-60 cell cDNA with isolated MZF-1 genomic clones indicated that the human MZF-1 gene is without introns and spans approximately 3 kb. Restriction enzyme mapping and Southern analysis indicated further that the human MZF-1 gene is a single-copy gene. Primer extension studies identified the major transcription start site as a thymidine residue located 1102 bp upstream of the ATG translation start codon. A putative TATA box sequence (TAAAAA) was found at -66 bp and a CCAAT box at -130 bp relative to the transcription initiation site. In HL-60 cells, MZF-1 mRNA levels are increased by granulopoietic inducers including retinoic acid and GM-CSF. DNA upstream of the transcription start site contains tandem-repeated consensus retinoic acid response elements at -666 through -696 bp and paired putative GM-CSF-responsive sequences centered at -50 and -100 bp. CAT reporter gene constructs containing these DNA regions promoted transcription and conferred transcriptional responsiveness to retinoic acid and GM-CSF when transfected into HL-60 cells. Additional putative regulatory binding sites included conserved MZF-1 zinc finger binding sequences, the importance of which was suggested by the enhanced expression of the endogenous MZF-1 gene following vector-driven expression of MZF-1 constructs in K562 myeloblastic leukemia cells. These findings provide a clearer basis for understanding the role of MZF-1 gene expression in myeloid cell growth and differentiation.

Base Sequence↗