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T C Wu

Publications and source records attributed to T C Wu.

At least 19 recordsLinked to original sources
PubMed2025

A randomized pilot study of HPV16 L2E7E6 fusion protein vaccination site post-treatment for HPV16+ cervical cancer.

OBJECTIVE: Since anti-tumor immunity is enhanced by vaccination of mice adjacent to human papillomavirus type 16 (HPV16+) tumors, we examined whether HPV16 L2E7E6 fusion protein (TA-CIN) vaccination in the thigh of HPV16+ cervical cancer patients would be more immunogenic than their arm. METHODS: HPV16+ cervical cancer (stage IB1-IVA) patients, who had completed standard-of-care treatment within the past year and absent evidence of disease (NED), were enrolled in a pilot study (NCT02405221). Participants were randomized 1:1 to receive three 100 μg TA-CIN monthly intramuscular immunizations either in the arm or thigh and followed for two years for safety (CTCAEv4.0), immune response, and recurrence. RESULTS: Fifteen patients were enrolled (median age 44, range 35-83 years); one patient experienced a non-vaccine-related adverse event after one vaccination and withdrew. Treatment-related adverse events (n = 8) were grade 1, primarily at the injection site, and self-resolved. No recurrence was observed. TA-CIN-specific antibody titers tended to be higher in thigh-vaccinated patients. Bulk TCRseq revealed significant increases in expanded and de novo T cell clones following thigh-vaccination compared with the arm. No correlation with prior treatment modality was observed. E6-, E7-, and L2-specific TCR clones expanded, although L2-specific T cell responses were predominant. One month post-vaccination, scRNAseq revealed significant expansion of MAIT and cytotoxic CD8+ T cells, and both expanded and novel TCR clonotypes were identified in the latter. CONCLUSIONS: Thigh or arm vaccination with TA-CIN was well tolerated, but the former elicited higher CD8 T cell and antibody responses in HPV16+ cervical cancer patients with NED after primary therapy.

Humans↗
PubMed1999

Targeting human papillomavirus type 16 E7 to the endosomal/lysosomal compartment enhances the antitumor immunity of DNA vaccines against murine human papillomavirus type 16 E7-expressing tumors.

DNA vaccination is an attractive approach for tumor immunotherapy because of its stability and simplicity of delivery. Advances demonstrate that helper T cell responses play a critical role in initiating immune responses. The aim of the current study is to test whether targeting HPV-16 E7 to the endosomal/lysosomal compartment can enhance the potency of DNA vaccines. We linked the lysosome-associated membrane protein 1 (LAMP-1) to HPV-E7 to construct a chimeric DNA, Sig/E7/LAMP-1 DNA. For in vivo tumor prevention experiments, mice were vaccinated with E7 DNA or Sig/E7/LAMP-1 DNA via gene gun, followed by tumor challenge. For in vivo tumor regression experiments, mice were first challenged with tumor cells and then vaccinated with E7-DNA or Sig/E7/LAMP-1 DNA. Intracellular cytokine staining with flow cytometry analysis, cytotoxic T lymphocyte (CTL) assays, enzyme-linked immunoabsorbent assay (ELISA), and enzyme-linked immunospot (ELISPOT) assays were used for in vitro E7-specific immunological studies. In both tumor prevention and tumor regression assays, Sig/E7/LAMP-1 DNA generated greater antitumor immunity than did wild-type E7 DNA. In addition, mice vaccinated with Sig/E7/LAMP-1 DNA had greater numbers of E7-specific CD4+ helper T cells, higher E7-specific CTL activity, and greater numbers of CD8+ T cell precursors than did mice vaccinated with Sig/E7 or wild-type E7 DNA. Sig/E7 generated a stronger E7-specific antibody response than did Sig/E7/LAMP-1 or wild-type E7 DNA. Our results indicate that linkage of the antigen gene to an endosomal/lysosomal targeting signal may greatly enhance the potency of DNA vaccines.

Animals↗
PubMed1999

Differential coronary microvascular function in patients with left ventricular dysfunction of unknown cause--implication for possible mechanism of myocardial ischemia in early stage of cardiomyopathy.

To evaluate whether or not coronary microvascular dysfunction is associated with exercise-induced myocardial ischemia in left ventricular dysfunction of unknown cause, both the treadmill exercise test (TET) and coronary hemodynamics were studied in 20 patients with impaired left ventricular ejection fraction (<50% by radionuclide ventriculogram), normal cardiac size, normal coronary angiogram and no evidence of clinical heart failure. Ten subjects with atypical chest pain were studied as the control. Coronary hemodynamics were studied both at baseline and after dipyridamole infusion (0.56mg/kg, i.v. for 4'). There was no difference in age, gender, blood pressure, baseline great cardiac venous flow (GCVF) and coronary vascular resistance between ten patients with a positive TET and the other ten with a negative TET. At baseline, coronary sinus oxygen concentration was increased and myocardial oxygen consumption reduced in patients with a positive TET compared with those with negative a TET. After dipyridamole infusion, maximum GCVF (102+/-47 vs. 144+/-31 ml/min, P=0.027) and coronary flow reserve (2.31+/-0.49 vs. 3.00+/-0.61, P=0.012) were significantly reduced and minimum coronary vascular resistance was higher (1.00+/-0.42 vs. 0.63+/-0.12 mmHg/ml/min, P=0.016) in patients with a positive TET than in those with a negative TET. At follow-up, 40% of patients with a positive TET and 10% of those with a negative TET developed clinical heart failure with a dilated left ventricle during a period of 45 months. Thus, coronary microvascular function is heterogeneous in patients with left ventricular dysfunction of unknown cause. In some of them, coronary microvascular dysfunction could be related to the presence of exercise-induced myocardial ischemia, suggesting that similar pathophysiology underlies the early stage of dilated cardiomyopathy and syndrome X.

Adult↗
PubMed1999

Competitive inactivation of a double-strand DNA break site involves parallel suppression of meiosis-induced changes in chromatin configuration.

In Saccharomyces cerevisiae, DNA double-strand breaks (DSBs) initiate meiotic recombination at open sites in chromatin, which display a meiosis-specific increase in micrococcal nuclease (MNase) sensitivity. The arg4 promoter contains such a DSB site. When arg4 sequences are placed in a pBR322-derived insert at HIS4 (his4 :: arg4 ), the presence of strong DSB sites in pBR322 sequences leads to an almost complete loss of breaks from the insert-borne arg4 promoter region. Most of the MNase-sensitive sites occurred at similar positions in insert-borne and in normal ARG4 sequences, indicating that hotspot inactivation is not a consequence of changes in nucleosome positioning. However, a meiosis-specific increase in MNase hypersensitivity was no longer detected at the inactive insert-borne arg4 DSB site. Elimination of pBR322 sequences restored DSBs to the insert-borne arg4 promoter region and also restored the meiotic induction of MNase hypersensitivity. Thus, the meiotic induction of MNase hypersensitivity at the DSB sites is suppressed and activated in parallel to DSBs themselves, without changes in the underlying DNA sequence or nucleosome positioning. We suggest that meiosis-specific changes in chromatin at a DSB site are a signal reflecting a pivotal step in DSB formation.

Argininosuccinate Lyase↗
PubMed1999

Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion.

Uncoupling protein 2 (UCP2) uncouples respiration from oxidative phosphorylation and may contribute to obesity through effects on energy metabolism. Because basal metabolic rate is decreased in obesity, UCP2 expression is predicted to be reduced. Paradoxically, hepatic expression of UCP2 mRNA is increased in genetically obese (ob/ob) mice. In situ hybridization and immunohistochemical analysis of ob/ob livers demonstrate that UCP2 mRNA and protein expression are increased in hepatocytes, which do not express UCP2 in lean mice. Mitochondria isolated from ob/ob livers exhibit an increased rate of H+ leak which partially dissipates the mitochondrial membrane potential when the rate of electron transport is suppressed. In addition, hepatic ATP stores are reduced and these livers are more vulnerable to necrosis after transient hepatic ischemia. Hence, hepatocytes adapt to obesity by up-regulating UCP2. However, because this decreases the efficiency of energy trapping, the cells become vulnerable to ATP depletion when energy needs increase acutely.

Adenosine Triphosphate↗
PubMed1999

Mitochondrial proteins that regulate apoptosis and necrosis are induced in mouse fatty liver.

Fatty liver is common in nonalcoholic, obese individuals and in lean people who consume alcohol chronically. Although fatty liver is typically benign, a subset of individuals with steatosis develop steatohepatitis and eventually cirrhosis. The disparate outcomes of fatty liver suggest that it reflects a generally beneficial, adaptive response to obesity or alcohol-related stress, but may also increase hepatocyte vulnerability to other challenges. Thus, both protective factors (e.g., Bcl-2 and Bcl-xL) and factors that promote hepatocyte death by apoptosis (e.g., Bax) or necrosis (e.g., UCP2) may be increased in fatty livers. To evaluate this possibility, hepatocyte apoptosis, necrosis, and the expression of factors that regulate cellular viability were assessed in two models of fatty liver (i.e., genetically obese [ob/ob] mice and ethanol [EtOH]-fed lean mice). Findings in mice with fatty livers were compared with lean, control mice that did not have hepatic steatosis. Immunohistochemistry showed striking induction of hepatocyte proteins that promote (e.g., Bax) and inhibit (e.g., Bcl-2 and Bcl-xL) apoptosis in both groups with fatty liver. Both models of fatty liver also increased hepatic transcripts for UCP2, a mitochondrial uncoupling protein, and the protein itself was induced in ob/ob hepatocytes. Despite the up-regulation of factors that threaten cell viability, hepatocyte death was not increased in either ob/ob or EtOH-fed mice, confirming that the liver's protective responses were sufficient under the conditions studied. However, if UCP2 induction reduces the efficiency of adenosine triphosphate (ATP) synthesis, this initially harmless response might enhance the vulnerability of hepatocytes to necrosis.

Animals↗
PubMed1999

Prediction of the rates of fertilization, cleavage, and pregnancy success by cumulus-coronal morphology in an in vitro fertilization program.

OBJECTIVE: To examine the relation between the grading of cumulus-coronal morphology at oocyte retrieval and the rates of fertilization, cleavage, and pregnancy success in IVF-ET cycles. DESIGN: Retrospective study. SETTING: University-affiliated medical center. PATIENT(S): Infertile women who underwent IVF-ET treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization and cleavage of the oocytes and the pregnancy outcome. RESULT(S): Mature grade 3 cumulus-oocyte complexes (COCs) constituted the highest percentage among all grades and had a higher fertilization rate than COCs of other grades (77% versus 65%, 43%, and 28% for grades 2, 1, and 4, respectively). The cleavage and polyspermy rates did not correlate with cumulus-coronal morphology grading. The pregnancy rate was higher in cycles with >50% grade 3 COCs than in cycles with < or =50% grade 3 COCs (32% versus 16%). In cycles with >80% grade 3 COCs, the pregnancy rate was 57%. The correlation between the percentage of grade 3 COCs and the pregnancy rate was independent of patient age and the number of COCs retrieved. CONCLUSION(S): The cumulus-coronal morphology grade correlates with the fertilization rate but not with the cleavage or polyspermy rate. In vitro fertilization cycles that have a greater percentage of grade 3 COCs have an increased chance of resulting in pregnancy. The cumulus-coronal morphology grade predicts pregnancy success in IVF-ET cycles.

Adult↗
PubMed1999

HPV in situ hybridization with catalyzed signal amplification and polymerase chain reaction in establishing cerebellar metastasis of a cervical carcinoma.

We report an unusual case of cerebellar metastasis from a cervical adenosquamous carcinoma in which molecular techniques assisted in establishing the correct diagnosis. The patient was a 43-year-old woman with surgically unresectable cervical carcinoma diagnosed 2 years before presenting with neurological symptoms. A magnetic resonance imaging scan showed a large, enhancing cerebellar lesion with significant brain stem compression. The excised cerebellar tumor resembled a small cell carcinoma and was initially not thought to be a metastasis from the cervical adenosquamous carcinoma. In situ hybridization with catalyzed signal amplification and polymerase chain reactions with primers specific for human papilloma virus (HPV) types 16 and 18 were used to determine the relationship between the cervical and the cerebellar neoplasms. A positive signal was present in the nuclei of both neoplasms by in situ hybridization using HPV16/18 DNA probes. Polymerase chain reaction revealed the presence of HPV-18 DNA sequences in the cervical and cerebellar neoplasms confirming that the cerebellar neoplasm was a metastasis from the cervical primary.

Adult↗
PubMed1999

Use of a recombination reporter insert to define meiotic recombination domains on chromosome III of Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, meiotic recombination is initiated by DNA double-strand breaks (DSBs). DSBs usually occur in intergenic regions that display nuclease hypersensitivity in digests of chromatin. DSBs are distributed nonuniformly across chromosomes; on chromosome III, DSBs are concentrated in two "hot" regions, one in each chromosome arm. DSBs occur rarely in regions within about 40 kb of each telomere and in an 80-kb region in the center of the chromosome, just to the right of the centromere. We used recombination reporter inserts containing arg4 mutant alleles to show that the "cold" properties of the central DSB-deficient region are imposed on DNA inserted in the region. Cold region inserts display DSB and recombination frequencies that are substantially less than those seen with similar inserts in flanking hot regions. This occurs without apparent change in chromatin structure, as the same pattern and level of DNase I hypersensitivity is seen in chromatin of hot and cold region inserts. These data are consistent with the suggestion that features of higher-order chromosome structure or chromosome dynamics act in a target sequence-independent manner to control where recombination events initiate during meiosis.

Argininosuccinate Lyase↗
PubMed1999

Acute basagran poisoning mimicking neuroleptic malignant syndrome.

A 27-year-old robust man, without any medical and surgical history, attempted to commit suicide by consumption of 300 cc (44.1%, 132.3 g) basagran, a readily available herbicide. This poisoning resulted in vomiting, fever, sweating, pipe-like muscle rigidity, sinus tachycardia, drowsiness, leukocytosis, rhabdomyolysis and hepatorenal damage. Emperical treatment with bromocriptine was temporally associated with resolution of above signs and symptoms. His clinical presentations and the effect of bromocriptine may be indicative that basagran poisoning mimicks neuroleptic malignant syndrome.

Adult↗
PubMed1998

Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein.

An important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported a recombinant vaccinia-based vaccine (Sig/E7/LAMP-1) that demonstrated significant anti-tumor effect in a subcutaneous tumor challenge model. In this study, we investigated the potency of the Sig/E7/ LAMP-1 vaccine in preventing and treating metastatic tumors. A tumor metastasis model was generated by injecting human papillomavirus type 16 (HPV-16) E6/E7 expressing tumor cells, designated TC-1, into the tail vein of syngeneic C57BL/6 mice. All the naive mice injected with 1 x 10(6) TC-1 cells developed tumors confined exclusively to the lungs within 1 month. For in vivo tumor prevention experiments, mice were vaccinated with Sig/E7/ LAMP-1 followed by tumor challenge. While tumor growth was observed in all of the mice (10/10) in the control groups, 8 of 10 vaccinated mice (80%) remained tumor-free 2 months post-tumor challenge. For in vivo treatment experiments, mice were first inoculated with TC-1 cells and then vaccinated with Sig/E7/ LAMP-1. Treatment with Sig/E7/LAMP-1 was effective in eliminating preexisting tumor cells in 4 of 5 vaccinated mice. Most importantly, treatment with Sig/E7/LAMP-1 resulted in regression of fully established lung tumors in 10% (5/10) of vaccinated mice. Our data suggest that the Sig/E7/LAMP-1 vaccine is effective in controlling the hematogenous spread of TC-1 tumor cells. In addition, the TC-1 lung metastasis model can be used to test the efficacy of various E6/E7-specific vaccines and immunotherapeutic strategies.

Animals↗
PubMed1998

Cellular proliferation, estrogen receptor, progesterone receptor, and bcl-2 expression in GnRH agonist-treated uterine leiomyomas.

Gonadotropin-releasing hormone (GnRH) agonists are commonly used in the treatment of uterine leiomyomas, but little is known about their histological and cellular effects on these neoplasms. We examined a cellular proliferation index as determined by the nuclear antigen Ki-67 and proliferating cell nuclear antigen (PCNA) expression, estrogen receptor (ER), and progesterone receptor (PR) expression in 27 leiomyomas from patients treated with the GnRH agonist leuprolide acetate (LA) and compared them with 33 untreated controls. All leiomyomas were removed by myomectomies from premenopausal woman after 2 to 6 months of LA treatment or in the follicular phase of the menstrual cycle in the untreated controls. Histological features examined included cellularity, nuclear atypia, vascular changes (dilated, thickened, or thrombosed vessels), edema, calcification, hemorrhage, necrosis, hyalinization, and mitotic activity. Although no difference was found between GnRH-treated and nontreated groups with respect to most histological features examined, immunohistochemical studies showed a significant decrease in the cellular proliferation index, ER, and PR expression in the LA-treated cases compared with nontreated controls. The cellular proliferation index, ER, and PR expression decreased by 85%, 49%, and 36%, respectively, in the LA-treated group as compared with controls (P < .001). A subset of cases from the LA-treated and nontreated groups were also analyzed with respect to bcl-2 (an inhibitor of apoptosis) expression, and no significant difference between the LA-treated and nontreated groups was observed with both groups showing a strong (> 75% of cells) cytoplasmic staining pattern. Results of this study show that LA treatment of leiomyomas results in a decrease in number of cycling cells.

Adult↗
PubMed1998

Correlation of plasma clearance of 54 extensively metabolized drugs between humans and rats: mean allometric coefficient of 0.66.

PURPOSE: To evaluate the distribution of allometric exponents for relationship of total plasma clearance of 54 extensively metabolized drugs, with wide-ranging linear clearance values, between humans and rats, to provide a rationale for the observed data, and to discuss potential significance of the findings. METHODS: Human and rat plasma clearance values of 54 drugs with markedly different physicochemical properties were obtained from the literature. Standard allometric analysis was performed for each drug using both rat and human data. Unbound vs. total plasma clearances were obtained for 15 out of 54 drugs and their correlations between humans and rats were compared. RESULTS: The mean+/-SD of the allometric exponent for the 54 drugs studied is 0.660+/-0.190. The median clearance ratio based on unit body weight is 7.41 and the median exponent is 0.645. Excluding two outliers the correlation coefficient of plasma clearance between humans and rats was 0.745 (p < 0.0001). For the 15 drugs, use of unbound plasma clearance approach seems to significantly improve the correlation coefficient compared to total plasma clearance (0.940 vs. 0.841). CONCLUSIONS: The present study indicates that on average, humans and rats may eliminate extensively metabolized drugs at a rate similar to that expected from the allometric or body surface area relationship of basal metabolic rate between the two species. A simple statistical distribution hypothesis is used to rationalize the species difference in plasma drug clearance. Rat may serve as an useful animal model to predict (unbound) plasma clearance of drugs in humans.

Animals↗
PubMed1998

Calcium oxalate is the main toxic component in clinical presentations of alocasis macrorrhiza (L) Schott and Endl poisonings.

Alocasia macrorrhiza (L) Schott and Endl is called Hai Yu, Tien Ho, Shan Yu, Kuan Yin Lien, Tu Chiao lien, Lao Hu Yu and Lang Du in Chinese. Its common English name is Giant Elephant's Ear. The toxic effects of A macrorrhiza arise from sapotoxin and include gastroenteritis and paralysis of the nerve centers. From 1985 to 1993 all individuals who called the Poison Control Center asking for information regarding macrorrhiza were included in this retrospective study. A questionnaire filled out by the Poison Control Center staff collected the demographic data of the victim, the reason for consumption, the prescribed part, clinical symptoms and signs of the victim, and medical outcome of poisonings. Among 27 cases of A macrorrhiza poisoning, the age was 1.5 to 68 y with 12 females and 15 males. One had skin contact and 1 had eye contact. In the 25 cases that consumed the plant leaf or tuber either raw or cooked, the primary symptom was in injected sore throat and the secondary symptom was numbness of the oral cavity. Some patients had salivation, dysphonia, abdominal pain, ulcers of the oral cavity, difficulty in swallowing, thoracodynia, chest tightness and swollen lips. We believe the presence of sapotoxin alone is not sufficient to explain the injected swollen and ulcerative lesions. Calcium oxalate is reported distributed in the entire plant and results in inflammation of the oral cavity and mucous membranes just as our patients had.

Adolescent↗
PubMed1998

Intracerebral hemorrhage in a young woman with arteriovenous malformation after taking diet control pills containing phenylpropanolamine: a case report.

Administration of phenylpropanolamine (PPA) is a rare cause of intracerebral hemorrhage. We present the case of a young female patient with arteriovenous malformation who suffered an intracerebral hemorrhage after ingestion of diet pills containing PPA. The literature on PPA-related intracerebral hemorrhage is also reviewed. This is the first report of PPA-associated intracerebral hemorrhage in a patient with pathology-proven arteriovenous malformation of the brain. Because intracerebral hemorrhage may develop as a side effect of PPA when patients take the manufacturer's recommended dose, especially in patients with vascular abnormalities, we conclude that this medicine should be prescribed carefully and patients should be closely monitored by experienced physicians. Furthermore, its use should be contraindicated in patients who have, or possibly have, a family history of vascular abnormalities.

Adult↗
PubMed1998

Generation of type-specific probes for the detection of single-copy human papillomavirus by a novel in situ hybridization method.

The integration of human papillomavirus (HPV) DNA is associated with the pathogenesis of HPV-associated malignancies. The ability, however, of standard in situ hybridization (ISH) to detect low-copy integrated HPV DNA is limited. We describe the generation of HPV type-specific biotin-labeled DNA probes and a novel ISH method that uses the catalyzed reporter deposition (CARD) system for the detection of single-copy target HPV DNA in formalin-fixed, paraffin-embedded tissue. Consensus primers flanking the noncoding region of HPVs were used to generate biotin-labeled HPV-6b, -11, -16 and -18 probes by polymerase chain reaction (PCR). The probes were used for ISH with the novel technique of CARD to increase the sensitivity of the assay. Tissue blocks were prepared from CaSki (500-600 copies of HPV-16), SiHa (1-2 copies of HPV-16), and HeLa (10-50 copies of HPV-18) cell lines, as well as from an HPV-negative cell line, C33A, and then tested to demonstrate the sensitivity and specificity of the probes. Surgical specimens were used to show the clinical applicability of this technique. We successfully detected HPV-16 DNA in CaSki and SiHa cells but not in HeLa or C33A cells. HPV-18 DNA was detected in HeLa cells but not in CaSki, SiHa, or C33A cells. Sensitivity was increased when ISH was performed using probes with more biotin incorporation or when more cycles of signal amplification were employed, but significant nonspecific background was observed after more than two cycles of signal amplification. The probes generated in this study detected specific types of HPV in surgical specimens with much higher sensitivity than did conventional ISH. We concluded that our new method was highly sensitive and could be applied to formalin-fixed, paraffin-embedded clinical material for the detection of HPV.

Carcinoma↗
PubMed1997

Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group.

BACKGROUND: A nationwide hepatitis B vaccination program was implemented in Taiwan in July 1984. To assess the effect of the program on the development of hepatocellular carcinoma, we studied the incidence of this cancer in children in Taiwan from 1981 to 1994. METHODS: We collected data on liver cancer in children from Taiwan's National Cancer Registry, which receives reports from each of the country's 142 hospitals with more than 50 beds. Data on childhood liver cancer were also obtained from Taiwan's 17 major medical centers. To prevent the inclusion of cases of hepatoblastoma, the primary analysis was confined to liver cancers in children six years of age or older. Data were also obtained on mortality from liver cancer among children. RESULTS: The average annual incidence of hepatocellular carcinoma in children 6 to 14 years of age declined from 0.70 per 100,000 children between 1981 and 1986 to 0.57 between 1986 and 1990, and to 0.36 between 1990 and 1994 (P<0.01). The corresponding rates of mortality from hepatocellular carcinoma also decreased. The incidence of hepatocellular carcinoma in children 6 to 9 years of age declined from 0.52 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (P<0.001). CONCLUSIONS: Since the institution of Taiwan's program of universal hepatitis B vaccination, the incidence of hepatocellular carcinoma in children has declined.

Adolescent↗