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Biomedical subjects

B W Park

Publications and source records attributed to B W Park.

14 recordsLinked to original sources

Health-related quality of life in disease-free survivors of breast cancer with the general population.

BACKGROUND: Although most of the literature about health-related quality of life (HRQoL) focuses on breast cancer patients, few studies compared the HRQoL in disease-free breast cancer survivors with that of the general population. MATERIALS AND METHODS: We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Breast Cancer Module, McGill Quality of Life Questionnaire, Beck Depression Inventory, and Brief Fatigue Inventory to 1933 disease-free survivors for over 1 year after being diagnosed with stage 0 to III breast cancer. We performed multivariate-adjusted analyses in all HRQoL comparisons. RESULTS: The scores for some health-related quality of life [corrected] HRQoL scales were comparable for both disease-free breast cancer survivors and the general female population, but [corrected] there was a [corrected] clinically significant difference between the two groups [corrected] in cognitive and social functioning, fatigue, insomnia, financial difficulties, body image, future perspective, breast symptoms, and arm symptoms. [corrected] CONCLUSIONS: Disease-free survivors of breast cancer had good HRQoL, which was less affected by the type of treatment than it was by demographic characteristics, time since surgery, comorbidity, fatigue, and depression.

Activities of Daily Living↗

Development of rat prostatitis model by oral administration of isoflavone and its characteristics.

Inflammation of the prostate can be induced experimentally in rats by the subcutaneous administration of estrogen. However, it is usually achieved at the price of some alteration in the sex steroid hormone balance and morphological changes in the prostate. In this study, a soy-extracted isoflavone mixture with weak estrogenic activity was administered orally in an attempt to induce prostatitis in a more physiologic way and to characterize the inflammation induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2 groups. The control group was fed with only an AIN-76A diet containing no detectable phytoestrogen and the experimental group was fed with AIN-76A and a soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300 mg/kg body weight for 9 weeks. The sequential body weight and prostate weight at necropsy were measured. A histologic examination and histomorphometry assessed the changes in the prostate. The serum concentrations of testosterone and dihydrotestosterone were measured to estimate the effects on the androgen level. Intraprostatic concentrations of genistein and daidzein were measured by gas chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation was apparent in the control group, severe inflammatory changes in the stroma, increased epithelial detachment and inflammatory exudates within the glandular lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the experimental group. However, there was no significant difference in the ventral prostate between the two groups. The daidzein and genistein concentrations in both the lateral and ventral prostates were significantly higher in the experimental group than in the control group where no isoflavone was detectable. In addition, the concentrations were much higher in the dorsolateral than in the ventral prostate. Although the body weight gain was not consistent in the experimental group, there were no significant differences in the prostate weight and serum androgen level between groups. In summary, when a soy-extracted genistein and daidzein-rich isoflavone mixture was administered orally into rats, prostatic inflammation with characteristic lobe specificity developed. The present method of inducing prostatitis seems to be a more physiologic than an estrogen-induced experimental model, and sequential pharmacokinetic studies might help in establishing this model as a more valuable tool in assisting future research in this field.

Administration, Oral↗

Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo.

Monoclonal antibodies specific for the p185HER2/neu growth factor receptor represent a significant advance in receptor-based therapy for p185HER2/neu-expressing human cancers. We have used a structure-based approach to develop a small (1.5 kDa) exocyclic anti-HER2/neu peptide mimic (AHNP) functionally similar to an anti-p185HER2/neu monoclonal antibody, 4D5 (Herceptin). The AHNP mimetic specifically binds to p185HER2/neu with high affinity (KD=300 nM). This results in inhibition of proliferation of p185HER2/neu-overexpressing tumor cells, and inhibition of colony formation in vitro and growth of p185HER2/neu-expressing tumors in athymic mice. In addition, the mimetic sensitizes the tumor cells to apoptosis when used in conjunction with ionizing radiation or chemotherapeutic agents. A comparison of the molar quantities of the Herceptin antibody and the AHNP mimetic required for inhibiting cell growth and anchorage-independent growth showed generally similar activities. The structure-based derivation of the AHNP represents a novel strategy for the design of receptor-specific tumor therapies.

Animals↗

Clinical breast examination for screening of asymptomatic women: the importance of clinical breast examination for breast cancer detection.

Of 489 asymptomatic women who were referred to our institute from other screening clinics, 46 were eventually proven to be breast cancer patients, and this number equated to 8.1% of the 565 breast cancer patients treated in our institute during the period of January 1997 to December 1998. Among the 46 cancer patients of the initial 489 asymptomatic women, twenty-five (54.35%) were detected by mammogram alone, six (13.04%) by clinical breast examination (CBE) alone, and the remaining 15 (32.61%) by both mammogram and CBE. In context with age, the mammographic sensitivity for cancer detection was 100% for women aged over 60, 91% for 50s, 78.9% for 40s, and 75% for 30s, and inversely correlated with the patient's age. Among the 25 cancers detected by mammogram alone, 18 (72%) belonged to DCIS or stage I. In contrast, four (66.7%) of six cancers detected by CBE alone and nine (60%) of 15 cancers by both CBE and mammography were included in stage IIa or IIb. However, the total incidence of early cancers (stages 0 and I) was significantly higher in the screening group than in the symptomatic group (p < 0.01). These results suggest that the role of mammography is important in the detection of cancers in their earlier stage and CBE is helpful in reducing false negative results in breast cancer screening. In conclusion, film mammography is the best tool for the detection of microcalcification and is useful for the detection of earlier lesions, but is not perfect for the detection of breast cancer particularly in young women. A careful CBE is an essential part of breast screening in order to reduce false-negative results.

Adult↗

Induction of the Tat-binding protein 1 gene accompanies the disabling of oncogenic erbB receptor tyrosine kinases.

Conversion of a malignant phenotype into a more normal one can be accomplished either by down-regulation of erbB family surface receptors or by creating inactive erbB heterodimers on the cell surface. In this report, we report the identification and cloning of differentially expressed genes from antibody-treated vs. untreated fibroblasts transformed by oncogenic p185(neu). We repeatedly isolated a 325-bp cDNA fragment that, as determined by Northern analysis, was expressed at higher levels in anti-p185(neu)-treated tumor cells but not in cells expressing internalization defective p185(neu) receptors. This cDNA fragment was identical in amino acid sequence to the recently cloned mouse Tat binding protein-1 (mTBP1), which has 98.4% homology to the HIV tat-binding protein-1 (TBP1). TBP1 mRNA levels were found to be elevated on inhibition of the oncogenic phenotype of transformed cells expressing erbB family receptors. TBP1 overexpression diminished cell proliferation, reduced the ability of the parental cells to form colonies in vitro, and almost completely inhibited transforming efficiency in athymic mice when stably expressed in human tumor cells containing erbB family receptors. Collectively, these results suggest that the attenuation of erbB receptor signaling seems to be associated with activation/induction or recovery of a functional tumor suppressor-like gene, TBP1. Disabling erbB tyrosine kinases by antibodies or by trans-inhibition represents an initial step in triggering a TBP1 pathway.

3T3 Cells↗

Conversion of a radioresistant phenotype to a more sensitive one by disabling erbB receptor signaling in human cancer cells.

Inhibition of cell growth and transformation can be achieved in transformed glial cells by disabling erbB receptor signaling. However, recent evidence indicates that the induction of apoptosis may underlie successful therapy of human cancers. In these studies, we examined whether disabling oncoproteins of the erbB receptor family would sensitize transformed human glial cells to the induction of genomic damage by gamma-irradiation. Radioresistant human glioblastoma cells in which erbB receptor signaling was inhibited exhibited increased growth arrest and apoptosis in response to DNA damage. Apoptosis was observed after radiation in human glioma cells containing either a wild-type or mutated p53 gene product and suggested that both p53-dependent and -independent mechanisms may be responsible for the more radiosensitive phenotype. Because cells exhibiting increased radiation-induced apoptosis were also capable of growth arrest in serum-deprived conditions and in response to DNA damage, apoptotic cell death was not induced simply as a result of impaired growth arrest pathways. Notably, inhibition of erbB signaling was a more potent stimulus for the induction of apoptosis than prolonged serum deprivation. Proximal receptor interactions between erbB receptor members thus influence cell cycle checkpoint pathways activated in response to DNA damage. Disabling erbB receptors may improve the response to gamma-irradiation and other cytotoxic therapies, and this approach suggests that present anticancer strategies could be optimized.

Apoptosis↗

Increased serum levels of transforming growth factor-alpha in patients with colorectal cancer.

PURPOSE: This study was conducted to investigate the serum levels of transforming growth factor-alpha in patients with colorectal cancer and to investigate the clinical significance of these levels in association with tumor stage and histologic differentiation. Also, serum levels of transforming growth factor-alpha were measured after curative surgical resection. METHODS: Serum levels of transforming growth factor-alpha were measured in 42 consecutive patients with colorectal cancer before surgery, in 21 patients after surgical resection (part of the 42 preoperative patients), and in 20 healthy volunteers. We used TGF-alpha Assay. RESULTS: Serum levels of transforming growth factor-alpha in patients with colorectal cancer were significantly higher than in the healthy control group (P = 0.001). Significant elevations in serum levels of transforming growth factor-alpha were found in 50 percent (21/42) of patients with colorectal cancer when the mean + 2 standard deviations (80.4 pg/ml) of the control group were used as the upper limit of the normal range. Serum levels of transforming growth factor-alpha tended to decrease with increasing tumor size (n = 31; r = -0.52; P = 0.002). Serum levels of transforming growth factor-alpha before surgery (89.7 +/- 44.4 pg/ml; n = 21) significantly decreased to 60.3 +/- 19.8 pg/ml after surgical resections of tumors (P = 0.017). Serum levels of transforming growth factor-alpha completely decreased to the same serum levels of the control group after surgical resections in all patients who had serum levels of transforming growth factor-alpha greater than mean + 2 standard deviations (80.4 pg/ml) of the control group preoperatively (n = 11; P = 0.002). CONCLUSIONS: Levels of preoperative transforming growth factor-alpha in patients with colorectal cancer appeared to be higher than levels measured in control subjects. Serum levels of transforming growth factor-alpha before surgery significantly decreased after surgical resections of tumors. Additional studies are warranted to determine if serum levels of transforming growth factor-alpha may be useful as a potential biomarker in the management of patients with colorectal cancer.

Adenocarcinoma↗

Increased serum levels of mutant p53 proteins in patients with colorectal cancer.

We have examined the serum levels of the mutant p53 protein in patients with colorectal cancer preoperatively (n=50), and in patients with adenomatous polyp (n=13). Mutant p53 protein in patients after curative surgical resection of colorectal cancer (n=26, part of the fifty preoperative patients) was also measured. Serum samples were stored frozen at -70 degrees C until the time of analysis. We used the p53 mutant ELISA (QIA03, CALBIOCHEM) system. Serum levels of the mutant p53 protein in patients with colorectal cancer (mean=0.97+/-0.14 ng/ml, ranged from 0.7 ng/ml to 1.37 ng/ml, n=50) were significantly greater than those in patients with adenomatous polyp (mean=0.73+/-0.06 ng/ml, ranged from 0.69 ng/ml to 0.83 ng/ml) (p<0.001). There was a significant correlation between serum p53 levels and CA19-9 levels (p<0.01). Serum levels of the mutant p53 protein prior to surgery (mean=0.97+/-0.13 ng/ml, n=26) significantly decreased after surgical resection of tumor (mean=0.82+/-0.07 ng/ml) (p<0.001, paired t-test). These results suggest that mutant p53 protein might be used as a potential biomarker in the management of patients with colorectal cancer. Further study is warranted to establish its clinical significance.

Adenomatous Polyps↗

Cloning and characterization of the citA gene encoding the mitochondrial citrate synthase of Aspergillus nidulans.

We isolated a citrate synthase gene (citA) from Aspergillus nidulans. By analysis of the protein coding region, citA was shown to encode a citrate synthase (CitA) of 52.2 kDa consisting of 474 amino acid residues that were interrupted by seven introns. Also, the precursor CitA protein was revealed to have an N-terminal mitochondrial targeting signal of 35 amino acid residues containing an R-3 cleavage motif, R(32)-C-Y decreases S(35), which supports the fact that citA encodes the mitochondrial form of citrate synthase of A. nidulans. Southern blot analysis showed that citA is present as a single copy in the genome.

Amino Acid Sequence↗

Comparison of PCR/nucleic acid hybridization and EIA for the detection of Chlamydia trachomatis in different populations in a regional centre.

Culture on McCoy cell monolayers has been accepted as the reference method for the detection of Chlamydia trachomatis. Recent studies have shown that polymerase chain reaction (PCR)/nucleic acid hybridization based methods have increased sensitivity over culture while still retaining specificity. In situations where organism viability is of concern, due to factors such as transportation delays, culture is inappropriate. Regional laboratories therefore have not been able to utilize the reference method and have been forced to use less reliable methods. The aims of our study were to assess the feasibility of performing PCR to diagnose infections due to C. trachomatis in a regional laboratory using a new commercial kit--Amplicor (Roche Molecular Systems, Branchburg, NJ) and to compare the current enzyme-immunoassay (EIA) based-methods used in our laboratory (VIDAS [bioMerieux Vitek, Hazelwood MO] and IDEIA [Novo Nordisk Diagnostics, Cambridge, UK]) against PCR. Thirteen positive Amplicor specimens were found in 267 urine specimens collected from asymptomatic adolescent males and females. All 13 were confirmed positive using major outer membrane protein gene PCR (MOMP). VIDAS and IDEIA showed 100% correlation to each other but only detected 5/13 positives. Of 140 consecutive patients attending the regional sexual health clinic, 13 were Amplicor positive, 11/13 MOMP positive and 10/13 positive by VIDAS. Five of 254 patients attending the hospital antenatal clinic were positive by Amplicor, all being confirmed by MOMP. No PCR inhibition was detected in a random sample of 100 varied negative Amplicor tests using a modification of the Amplicor kit. No contamination was experienced. The Amplicor kit was shown to be suitable for use in the routine clinical laboratory with minimal disruption to workflow. For regional laboratories this kit should provide more accurate results than EIA based methods, particularly in the detection of asymptomatic persons.

Adolescent↗

NO- and NO2-carrying molecules potentiate photorelaxation in rat trachea and aorta.

Photorelaxation elicited by ultraviolet light (366 nm) was investigated on isolated rat thoracic aorta and trachealis. Rat tracheal smooth muscle but not aorta did not show UV-induced photorelaxation. Both streptozotocin, NO-carrying molecule and N omega-nitro-L-arginine, NO2-carrying molecule significantly enhanced photorelaxation, concentration-dependently, in rat trachealis and aorta. Methylene blue (10 microM) inhibited the potentiation action of streptozotocin and N omega-nitro-L-arginine in both tissues. Superoxide dismutase (300 U/ml) enhanced streptozotocin- and N omega-nitro-L-arginine-potentiated photorelaxation in rat trachealis, while pyrogallol (0.1 mM), a potent O2- generating agent, inhibited streptozotocin-potentiated photorelaxation in trachealis. Streptozotocin was much more effective than N omega-nitro-L-Arginine in potentiating of photorelaxation elicited by UV light in both tissues. From these findings, we conclude that streptozotocin and N omega-nitro-L-arginine produce EDRF like labile substance(s) by UV irradiation.

Animals↗

Pyriform sinus fistula.

Three patients had cervical draining sinus communicating with the pyriform sinus and one patient had acute suppurative thyroiditis resulting from infection through the pyriform sinus. There was a moderate to severe perithyroidal inflammation in all 4 cases. The age of onset ranged from 7 to 18 years old (mean; 12) but that of confirmation 9, 15, 18 and 67 years of age. Three of the patients were male and 3 of the cases involved the left side. All patients had suffered from several recurrences of cervical abscess, ranged from 2 to 7 times (mean; 4). Characteristic clinical features included 1) onset at a young age 2) frequent recurrence unless the fistula was extirpated completely 3) presenting with cervical draining sinus after repeated incision and drainage. It is supposed that the fistula is a route of infection mainly in the perithyroidal space and subsequently into the thyroid gland. When the fistula communicates directly with the thyroid gland, it can cause primary acute suppurative thyroiditis. Chronic cervical draining sinus with histories of repeated incision and drainage may be the clue to the diagnosis. A barium paste swallow study is the radiologic procedure of choice and complete removal of the fistula is the treatment of choice.

Adult↗

Ductal eccrine carcinoma presenting as a Paget's disease-like lesion of the breast.

Some types of skin appendage tumors, particularly ductal eccrine carcinomas (DEC), imitate breast carcinomas histologically, thus causing great diagnostic challenges. We describe a case of DEC presenting as an eczematous, crusted skin lesion on the right nipple-areolar complex in a 67-year-old woman. A skin biopsy done under the clinical impression of Paget's disease of the nipple was initially misinterpreted as infiltrating ductal carcinoma, and a subsequent modified radical mastectomy revealed DEC exclusively confined to the nipple with perinodal tumor metastasis in one of the axillary lymph nodes. This case highlights the diagnostic difficulty caused by the histologic homology between breast carcinomas and skin appendage tumors with ductal differentiation.

Aged↗

[Functional variability of the autocorrelation structure of the EEG].

On an example of records EEG of 39 healthy subjects, the quantitative analysis of variability of the autocorrelation structure of one-second EEG segments was carried out on the basis of comparison of structural functions constructed for these segments. It was shown that more than 30% of cases, statistically significant sifferences were observed between the structural functions of successive one-second EEG segments shifted by 1-3 s, as compared to surrogate EEGs formed with the tangled random sequence of count points. On the basis of the obtained data, the index of nonstationarity of the EEG autocorrelation structure was proposed. This index can be used for the objective quantitative evaluation of the functional states of the human brain.

Brain↗