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Biomedical subjects

C C Wang

Publications and source records attributed to C C Wang.

At least 361 records · Page 20Linked to original sources
PubMed1995

Effects of Ganoderma lucidum and krestin on subset T-cell in spleen of gamma-irradiated mice.

Effects of Ganoderma lucidum (Gl) and Krestin (PSK) extracts on spleen, thymus and splenocytes in gamma-irradiated mice were investigated in this study. ICR strain male mice were divided into five groups. Group A was the normal control. Group B, the experimental control, was treated with Gl. Group C, the radiation treatment control, was treated with whole body exposure to 4 Gy gamma-irradiation (RT). Group D was treated with RT and Gl. Group E was treated with RT and PSK. The dosage of Gl was 400 mg/day/kg body weight and PSK was 500 mg/day/kg body weight. Our results indicated that the relative thymus weight in groups D and E were higher than group C on day 28 after gamma-irradiation. Group D was the highest in all the experimental groups. CD4 and CD8 splenocytes in group D were higher than group C on days 7 and 28. Gl was better than PSK in repairing the damage of subset T-cells in the spleen of gamma-irradiated mice.

Animals↗
PubMed1995

Molecular mechanisms and therapeutic approaches to the treatment of African trypanosomiasis.

There are only a handful of drugs available today for treating African trypanosomiasis, most of which were discovered more than forty years ago. These drugs are plagued by various problems, ranging from oral in-absorption, acute toxicities, short durations of action, and low efficacies to the emergence of trypanosomal resistance. Mechanisms of antitrypanosomal action of these drugs are mostly unknown, except for eflornithine, which is a suicide inhibitor of ornithine decarboxylase. On the other hand, the African trypanosomes are among the most extensively studied parasitic protozoa to date. Many of their intriguing biological features have been well documented and can be viewed as attractive targets for antitrypanosomal chemotherapy. These features include the glycosomal functions and protein import, the trans-splicing of mRNAs, the machineries for controlled protein degradations, the polyamine metabolism, the trypanothione metabolism, the purine salvage enzymes, and the glycolipid anchor for the surface glycoproteins.

Animals↗
PubMed1995

Effects of indomethacin on lymphokine-activated killer cell activities in cancer patients.

Prostaglandin E2 (PGE2) is known to downregulate the generation of lymphokine-activated killer (LAK) cell activity. Indomethacin, an inhibitor of cyclooxygenase catalyzing the biosynthesis of PGE2, has been shown to augment LAK cell activities generated from peripheral blood mononuclear cells of normal healthy individuals. This study was undertaken to examine whether or not this augmentation is also a common phenomenon in cancer patients. LAK cell activities generated in the presence and the absence of indomethacin were examined in 15 normal healthy individuals and in 83 cancer patients. Paired data analysis revealed that indomethacin exhibited a significant augmentation of LAK activity generated from healthy individuals. Indomethacin enhanced LAK activity in patients with no distant metastases (TxNxM0); but depressed LAK activity in patients with distant metastases (TxNxM1). In patients without distant metastases, indomethacin showed an upregulating effect on LAK activity in those with an early T stage (T1-2NxM0), and no such effect was detected in those with a late T stage (T3-4NxM0). Indomethacin also significantly enhanced LAK cell generation in cancer patients with an ECOG performance status of 1, but significantly inhibited LAK cell generation in patients with a performance status of 4. These results indicated that indomethacin inhibited generation of LAK cell activity in cancer patients with a poor performance status or with distant metastatic disease, who normally would be the subjects of adoptive immunotherapy. Further, PGE2 production in cultured LAK cell medium was suppressed by indomethacin in all 20 cancer patients that were examined, suggesting that other yet to be identified factors or mechanisms may be responsible for the paradoxical effects of indomethacin on LAK cell activity.

Adjuvants, Immunologic↗
PubMed1995

Local control of oropharyngeal carcinoma by irradiation alone.

The authors of this study reviewed the management of 402 patients with squamous cell carcinomas of the faucial tonsil and the base of the tongue. These patients received radiation therapy at Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary from 1970 through 1993. Radiation therapy remains the treatment of choice for these lesions. Although the data from this review were not randomized, the accelerated hyperfractionated radiation therapy twice-daily program was shown to achieve significantly higher 5-year local tumor control rates and disease-specific survival rates than the conventional once-daily radiation therapy program (historical control). In patients with early tumors of the faucial tonsil (cancer stages T1 and T2), the 5-year actuarial local tumor control and disease-specific survival rates following the twice-daily radiation therapy program were 91% and 77%, respectively. In patients with advanced tumors (T3), the corresponding rates following twice-daily radiation therapy showed marked improvement and were 80% and 68%. While the treatment results for carcinoma of the base of the tongue generally were inferior to those for carcinoma of the faucial tonsil, they were still much better after the twice-daily program than after conventional once-daily irradiation. For patients with carcinoma of the base of the tongue, the local tumor control and disease-specific survival rates for T1 and T2 lesions were 85% and 76%, respectively. For T3 lesions, the corresponding rates were 54% and 53%. Extensive T4 tumors are better managed by combined surgery and postoperative irradiation. Residual metastatic nodal disease is managed by neck dissection.

Actuarial Analysis↗
PubMed1995

Villous adenoma of ampulla of Vater: a case report.

A 56-year-old female patient presented with pain and tenderness over the epigastric region. Endoscopy showed a polypoid mass at the ampulla of Vater. Endoscopic biopsy showed villous adenoma with moderate cellular atypia. Wide excision of the tumor was performed. After resection, histological examination confirmed the tumor to be a villous adenoma of ampulla of Vater. This is a rare neoplasm with an incidence of 0.04-0.12% in postmortem series. A few cases have been reported in the literature, but only two documented in the Chinese literature to date. Wide excision has had good results and should be regarded as the treatment of choice for benign lesions.

Adenoma, Villous↗
PubMed1995

Combination chemoimmunotherapy with interferon-alpha and cisplatin in patients with advanced non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) has a relatively low response rate to systemic chemotherapy. Recently, several investigations have shown that interferon may augment the cytotoxic effect of chemotherapeutic agents and may improve the result of chemotherapy in treating cancers. METHODS: An open-label noncomparative phase II study investigated the efficacy and safety of combined chemoimmunotherapy for NSCLC using IFN-alpha, given by intramuscular injection with 9 million units thrice a week for a maximum of 26 weeks, and cisplatin by intravenous infusion, 100 mg/m2, every 4 weeks for a maximum of 6 cycles. Ten patients, with histology-confirmed NSCLC at stage IV of their diseases were enrolled. They included 5 men and 5 women, with an average age of 53.7 year. Five of them had adenocarcinoma; the other five had squamous cell carcinoma. RESULTS: Five patients, including two patients with squamous cell carcinoma and three with adenocarcinoma, obtained a partial response (response rate 50%). The time needed to achieve a sustained response ranged from 5 to 13 weeks with a median of 8 weeks. The response duration ranged from 14 to 37 weeks with a median of 20 weeks. The overall survival time for the ten patients ranged from 2 to 20 months with a median of 8 months. All 10 patients needed dose modifications of IFN-alpha and/or cisplatin because of myelosuppression and/or impaired renal function. Other frequently encountered side effects included gastrointestinal disturbances and a flu-like syndrome, but these were well tolerated. CONCLUSIONS: These preliminary results indicate that chemoimmunotherapy with IFN-alpha and cisplatin can be an effective alternative therapy for patients with advanced NSCLC, but there are significant side effects.

Adenocarcinoma↗
PubMed1995

Thyroglobulin measurement. Techniques, clinical benefits, and pitfalls.

The validity and reliability of serum Tg measurements is central to accurate diagnosis and cost-effective management of patients with differentiated thyroid carcinoma. Serum Tg is one of the most difficult biochemical tests for a laboratory to maintain at a high level of precision and reliability across the long clinical sampling interval typically employed when monitoring this condition. Physicians should be aware that the diagnostic value of serum Tg measurement is method-dependent, and that intermethod differences still approach 30% even after methods have been standardized on the new CBR reference preparation. This dictates that, ideally, serial serum Tg measurements in a patient should always be made in the same laboratory by the same method. Physicians need to consider a number of factors before selecting a laboratory to perform Tg measurements in patients with differentiated thyroid carcinoma. These factors include assay sensitivity, as judged by the discrimination between lower limit of the euthyroid range and the functional sensitivity limit, as well as assay specificity, especially with respect to serum TgAb interference. laboratories should use a sensitive TgAb immunoassay (not hemagglutination) to prescreen sera for TgAb and report the TgAb level if positive. Furthermore, it is the laboratory's responsibility to advise physicians fully about any change in Tg method as well as the direction of TgAb interference expected with that method. When TgAb is present, the serum Tg level should be a measure of the total (free and TgAb-bound) serum Tg level. Typically, IMA methods underestimate the serum total Tg level, especially when serum TSH is suppressed, whereas RIA methods tend to overestimate the serum total Tg level. The interpretation of a serum Tg level in a TgAb-positive patient should be made with caution and with consideration to any changes in TgAb levels. Serial TgAb monitoring of TgAb-positive patients may provide a physician with additional prognostic information on outcome. Precise, reproducible serial serum Tg measurements are critical, especially when patients are judged to have a high risk for recurrence, have tumors that are inefficient serum Tg secretors (as judged from the relationship between the preoperative serum Tg value and tumor mass or the serum Tg response to endogenous TSH stimulation), or have very high serum Tg values requiring dilution. In such patients, the banking of left-over sera (frozen) for concurrent intra-assay remeasurement with a more recent specimen significantly increases the clinical value of the test and facilitates earlier detection of recurrence or progression (see Fig. 2). Differentiated thyroid carcinoma is frequently diagnosed in young patients with decades of life expectancy. After their initial surgical treatment, these patients need life-long monitoring, because late recurrences and death from the disease can occur. The use of high-quality serum Tg measurements can significantly improve the cost-effective management of this disease by identifying low-risk patients in whom periodic radioiodine scans or therapy may be deferred in favor of serial serum Tg monitoring (on L-T4 suppression therapy). With this approach, expensive imaging procedures can be targeted to the minority of patients who are at high risk for recurrence.

Autoantibodies↗
PubMed1995

A method of stimulating an immune response with a hapten immobilized on a nitrocellulose membrane.

Hapten refers to a chemical compound of small molar mass (typically less than 1000 daltons) that can bind with an antibody, but cannot initiate an immune response by itself unless it is conjugated to a protein carrier of larger molar mass. A novel method to prepare a hapten to generate anti-hapten immunity without covalent conjugation to a carrier was developed. Coating both water-soluble and -insoluble haptens onto a nitrocellulose membrane effectively presented haptens to the system and caused the generation of specific anti-hapten B lymphocytes and antibodies by immunization both in vitro and in vivo. This method has a potential to substitute for conventional hapten carrier conjugation to generate anti-hapten immunity.

Adsorption↗
PubMed1994

Chaperone-like activity of protein disulfide isomerase in the refolding of a protein with no disulfide bonds.

D-Glyceraldehyde-3-phosphate dehydrogenase (GAP-DH) is a protein containing no disulfide bonds; the guanidine HCl-denatured enzyme shows only a limited extent of refolding and reactivation upon dilution, and the enzyme is particularly prone to aggregation during the dilution process. With increasing GAPDH concentration, reactivation decreases and aggregation increases. The presence of protein disulfide isomerase in the dilution mixture markedly increases reactivation of GAPDH and at the same time prevents the aggregation of GAPDH as shown by light-scattering measurements. It is suggested that upon dilution, denatured GAPDH is faced with two competing processes of correct folding and assembly to yield the native enzyme and non-productive association of the partially refolded species to form aggregates. Independent of the isomerase activity as no disulfide bond is present in GAPDH, protein disulfide isomerase assists the refolding of GAPDH to its active state by suppressing aggregation in a way closely similar to the action of chaperones.

Disulfides↗
PubMed1994

Phosphoenolpyruvate carboxykinase of Trypanosoma brucei is targeted to the glycosomes by a C-terminal sequence.

Import of proteins into the glycosomes of T. brucei resembles the peroxisomal protein import in that C-terminal SKL-like tripeptide sequences can function as targeting signals. Many of the glycosomal proteins do not, however, possess such C-terminal tripeptide signals. Among these, phosphoenolpyruvate carboxykinase (PEPCK (ATP)) was thought to be targeted to the glycosomes by an N-terminal or an internal targeting signal. A limited similarity to the N-terminal targeting signal of rat peroxisomal thiolase exists at the N-terminus of T. brucei PEPCK. However, we found that this peroxisomal targeting signal does not function for glycosomal protein import in T. brucei. Further studies of the PEPCK gene revealed that the C-terminus of the predicted protein does not correspond to the previously deduced protein sequence of 472 amino acids due to a -1 frame shift error in the original DNA sequence. Readjusting the reading frame of the sequence results in a predicted protein of 525 amino acids in length ending in a tripeptide serine-arginine-leucine (SRL), which is a potential targeting signal for import into the glycosomes. A fusion protein of firefly luciferase, without its own C-terminal SKL targeting signal, and T. brucei PEPCK is efficiently imported into the glycosomes when expressed in procyclic trypanosomes. Deletion of the C-terminal SRL tripeptide or the last 29 amino acids of PEPCK reduced the import only by about 50%, while a deletion of the last 47 amino acids completely abolished the import. These results suggest that T. brucei PEPCK may contain a second, internal glycosomal targeting signal upstream of the C-terminal SRL sequence.

Acetyl-CoA C-Acetyltransferase↗
PubMed1994

Frequent genetic alterations at the distal region of chromosome 1p in human hepatocellular carcinomas.

Cytogenetic analysis of hepatocellular carcinoma (HCC) cell lines and primary HCC tissues has demonstrated chromosome 1p to be the region most commonly affected. To refine the altered locus, genetic abnormalities of this region were surveyed systemically by microsatellite polymorphism analysis. Twelve sets of primers evenly distributed on chromosome 1p which can amplify di- or tetranucleotide repeat length polymorphism by polymerase chain reaction were selected. The results were then supplemented by the conventional restriction fragment length polymorphism study. A comparison of the allele patterns between 30 pairs of HCC and their corresponding nontumor DNAs discovered chromosome 1p aberrations in 15 of 30 tumors (50%). The abnormalities can be classified into three groups. The first aberration was typical loss of heterozygosity that was found in 9 HCCs (30%). The second aberration was a 2-3-fold increase of allelic dosage, which was detected in 6 HCCs (20%). The third aberration was the novel microsatellite polymorphism, which was detected in 3 cases (10%). These abnormalities seemed to cluster at the distal part of chromosome 1p, with a common region mapped to 1p35-36, which is also the region with frequent loss of heterozygosity in neuroblastoma and colorectal and breast cancers. Therefore, loss of putative tumor suppressor gene(s) in this locus may participate in the development of hepatocellular carcinoma and a wide range of human cancers.

Carcinoma, Hepatocellular↗
PubMed1994

Association and dissociation of protein disulfide isomerase.

Purified protein disulfide isomerase, homogeneous by SDS-PAGE, can be separated into two components by PAGE and by gel filtration. These two components, with the same amino-acid composition as well as N- and C-terminal sequences, are the tetramer and dimer of molecular weight 240 kDa and 120 kDa, respectively. The specific activity of the dimer is twice that of the tetramer. At 4 degrees C and pH 7.5 the purified dimer associates and the tetramer dissociates, both slowly and partially, to form a dimer-tetramer mixture. Treatment with dithiothreitol has only a minor effect on the dissociation of the tetramer indicating that the association is not through disulfide formation between the protomers. By prolonged treatment with 1% Triton X-100 or in strong salt solutions the tetramer dissociates to the dimer, but further dissociation to the monomer can only be effected in SDS or guanidine hydrochloride. These results suggest that apart from hydrogen bonds, hydrophobic forces and ionic interactions are mainly involved in the association of the protomers.

Binding Sites↗
PubMed1994

Differential inhibitory effects of GMP-2',3'-dialdehyde on human and schistosomal hypoxanthine-guanine phosphoribosyltransferases.

The hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) of human and the parasitic trematode, Schistosoma mansoni, were expressed at high levels in transformed Escherichia coli in their native forms. Guanosine 2',3'-dialdehyde 5'-phosphate (ox-GMP) was shown to bind irreversibly to both enzymes in a time-dependent manner. This binding was stabilized by sodium borohydride reduction, suggesting that a Schiff's base is formed between the dialdehyde groups of ox-GMP and the amino group of a lysine residue in the enzymes. This linkage formation applies also to inosine 2',3'-dialdehyde 5'-phosphate but not to adenosine 2',3'-dialdehyde 5'-phosphate. GMP was found to be protective against ox-GMP inactivation and [3H]ox-GMP labeling of both HGPRTases. 5-Phosphoribosyl-1-diphosphate (PRibPP) also protects human HGPRTase against the ox-GMP inactivation and [3H]ox-GMP labeling but provides virtually no protection against the ox-GMP inactivation and labeling of the schistosomal enzyme, even though PRibPP binds to the latter with a threefold higher affinity. These results imply that PRibPP and ox-GMP compete with each other for binding to the human HGPRTase but not for binding to the schistosomal enzyme. This discrepancy could be exploited for the purpose of designing selective inhibitors of the schistosomal HGPRTase. Guanosine 2',3'-dialdehyde (ox-guanosine) is nearly as active as ox-GMP in inhibiting schistosomal HGPRTase but much less potent in inhibiting human HGPRTase, suggesting that ox-guanosine and ox-GMP may bind equally well to the parasite enzyme. PRibPP can protect human but not schistosomal HGPRTase against the inactivation by ox-guanosine. Therefore, ox-GMP and ox-guanosine must be forming Schiff's bases with the same amino acid residues in each of the two HGPRTases.

Animals↗
PubMed1994

Does prolonged treatment course adversely affect local control of carcinoma of the larynx?

PURPOSE: The purpose of this paper is to present local control rates of carcinoma of the larynx in relation to the total treatment course after radical radiation therapy. METHODS AND MATERIALS: A total of 1350 patients with laryngeal carcinoma treated at the Massachusetts General Hospital for the past three decades were available for analysis. Treatment courses were divided into two groups: 45 days and > 45 days. The local control rates were compared and evaluated for statistical differences. RESULTS: The data indicated that prolonged treatment course adversely affects local tumor control of both advanced glottic and supraglottic lesions, but to a lesser degree for the early tumors. CONCLUSION: The study indicated that for optimal local control, radiation treatment should be completed as soon as possible, preferably within 6.5 weeks, either by once- or twice-daily accelerated programs. The local control of early T1 glottic cancer has been exceedingly satisfactory by conventional once-daily radiation therapy. Further improvement by shortening of treatment time for such early lesions will be difficult to assess without a prospective randomized trial.

Adult↗