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C Chao

Publications and source records attributed to C Chao.

At least 37 records · Page 2Linked to original sources
PubMed2000

Rescue of defective T cell development and function in Atm-/- mice by a functional TCR alpha beta transgene.

The Atm-/- mice recapitulate most of the defects observed in ataxia-telangiectasia (A-T) patients, including a high incidence of lymphoid tumors and immune defects characterized by defective T cell differentiation, thymus hypoplasia, and defective T-dependent immune responses. To understand the basis of the T cell developmental defects in Atm-/- mice, a functional TCR alpha beta transgene was introduced into these mutant mice. Analysis of the Atm-/-TCR alpha beta+ mice indicated that the transgenic TCR alpha beta can rescue the defective T cell differentiation and partially rescue the thymus hypoplasia in Atm-/- mice, indicating that thymocyte positive selection is normal in the Atm-/- mice. In addition, cell cycle analysis of the thymocytes derived from Atm-/-TCR alpha beta+ and control mice suggested that Atm is involved in the thymocyte expansion. Finally, evaluation of the T-dependent immune responses in Atm-/-TCR alpha beta+ mice indicated that Atm is dispensable for normal T cell function. Therefore, the defective T-dependent immune responses in Atm-/- mice must be secondary to greatly reduced T cell numbers in these mutant mice.

Animals↗
PubMed2000

Effects of parenteral infusion with medium-chain triglycerides and safflower oil emulsions on hepatic lipids, plasma amino acids and inflammatory mediators in septic rats.

This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using medium-chain triglycerides (MCT) versus safflower oil (SO) emulsion as fat sources on hepatic lipids, plasma amino acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were divided into two groups and received TPN. TPN provided 300kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or a mixture of MCT and soybean oil (9:1) (MO). After receiving TPN for 6 days, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture, whereas control rats received sham operation. All rats were classified into four groups as follows: MCT control group (MOC, n= 8), MCT sepsis group (MOS, n= 8), safflower oil control group (SOC, n= 8), and safflower oil sepsis group (SOS, n= 11). The results of the study demonstrated that the MOS group had lower hepatic lipids than did the SOS group. Plasma leucine and isoleucine levels were significantly lower in the SOS than in the SOC group, but no differences in these two amino acids were observed between the MOC and MOS groups. Plasma arginine levels were significantly lower in septic groups than in those without sepsis despite whether MCT or safflower oil was infused. Plasma glutamine and alanine levels, however, did not differ between septic and non-septic groups either in the SO or MO groups. No differences in interleukin-1b, interleukin-6, tumor necrosis factor-alpha, and leukotriene B(4)concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction is septic rats preinfused MCT is not as obvious as those preinfused safflower oil. Compared with safflower oil, TPN with MCT administration has better effects on reducing sepsis-induced liver fat deposition. Preinfusion with MCT before sepsis, however, had no effect on inflammatory-related cytokines or leukotriene in peritoneal lavage fluid. In addition, plasma arginine appears to be a more sensitive indicator than glutamine for septic insult.

Amino Acids↗
PubMed2000

Surgical salvage therapy: abdominoperineal resection for recurrent anal carcinoma, metastasectomy of recurrent colorectal cancer, and esophagectomy after combined chemoradiation.

This review highlights the advances in the salvage surgical therapies for recurrent disease after definitive therapy of anal carcinoma, colorectal cancer, including liver metastasectomy, and esophageal carcinoma treated primarily with chemoradiation. New diagnostic modalities, advances in neoadjuvant therapies for unresectable liver metastases, and, in addition, the importance of adjuvant hepatic arterial chemotherapy after curative liver resections are reviewed. Although chemoradiation is not the standard of care for esophageal cancer, salvage esophagectomy after such treatment is discussed. Definitive chemoradiation for squamous cell carcinoma of the anus has altered the role of surgical intervention to a salvage option instead of primary treatment. Although this is not yet the case for esophageal carcinoma, recent improved chemoradiation regimens have been reported by the French and Japanese, who use surgery for nonresponders. For recurrent colorectal carcinoma, including liver-only metastases, patients can be rendered disease free after surgical extirpation with evidence of improved survival. Appropriate surveillance in these patients may identify subsets of patients with disease amenable to resection.

Abdomen↗
PubMed2000

Analysis of treatment results for floor-of-mouth cancer.

OBJECTIVE: This study reports the results of treating floor-of-mouth cancer with five different treatment modalities with long-term follow-up. STUDY DESIGN: Retrospective study of 280 patients with floor-of-mouth cancer treated in the Department of Otolaryngology-Head and Neck Surgery at Washington University Medical School (St. Louis, MO) from 1960 to 1994. METHODS: Patients with biopsy-proven squamous cell carcinoma of the floor of mouth who were previously untreated were treated with curative intent by one of five modalities and were all eligible for 5-year follow-up. The treatment modalities included local resection alone, composite resection alone (with neck dissection), radiation therapy alone, local resection with radiation therapy, and composite resection with radiation therapy. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analysis to determine statistical significance. RESULTS: The overall 5-year disease-specific survival (DSS) was 56% with death due to tumor in 44% of patients. The 5-year cumulative disease-specific survival (CDSS) was 0.61 (Kaplan-Meier probability) with a mean of 8.3 years and a median of 9.7 years. The DSS by treatment modality included local resection (76%), composite resection (63%), radiation therapy (43%), local resection with radiation therapy (61%), and composite resection with radiation therapy (55%). Overall, there was no significant difference in DSS by treatment modality. Recurrence at the primary site (41%) was the most common site of treatment failure. Nineteen percent of patients had recurrence in the neck. Eighty-eight percent of initial recurrences occurred within 60 months after the onset of treatment. Metastasis to a distant site occurred in 30% of patients. Twenty percent of these patients had second primary cancers, and 53% of these patients died of their second primary cancers. CONCLUSIONS: Significantly improved 5-year DSS was seen in the patients with clear margins, early clinical tumor stage, and negative nodes. Significantly decreased 5-year survival was seen in the patients with involved margins, advanced clinical tumor stage, positive nodes, and tumor recurrence. Patients with no clinically positive nodes (cNO) can be observed safely for regional nodal disease and subsequent positive nodes can be treated as they occur with no adverse affect on survival. Because of high recurrence rates at the primary site and neck, and an increased rate of both distant metastasis and the development of second primary cancers, patients should be monitored closely for a minimum of at least 5 years.

Adolescent↗
PubMed2000

Pancreatic carcinoma deemed unresectable at exploration may be resected for cure: an institutional experience.

Only a minority of patients with a diagnosis of pancreatic adenocarcinoma (PA) have disease amenable to curative resection. Between April 1987 and March 1999, 40 patients with pancreatic adenocarcinoma deemed unresectable at exploration at other institutions were considered for neoadjuvant treatments and then re-evaluated for possible re-exploration. We retrospectively compared the clinical outcomes, including overall survival (OS), among three groups: Group A, 22 previously unresectable patients who were subsequently successfully resected, 20 after induction therapy; Group B, 31 patients who received preoperative chemoradiotherapy before their only operation; and Group C, 33 patients who were primarily resected, 27 of whom were then treated with adjuvant therapy. Of those resectable from Group A, 5 required portal venorrhaphy and 3 had hepatic artery reconstruction. Eighteen of the 40 patients were unresectable because of progression of disease with a mean OS of 8 months; 12 were assessed at second laparotomy; 6 were excluded from second operation on the basis of preoperative imaging studies. Kaplan-Meier curves showed no differences in OS among the three groups: OS in Group A was 34 months; Group B, 21; and Group C, 13 (P = 0.15). Margin status was comparable in all three groups (P = 0.52). As expected, nodal positivity was greatest in Group C (P = 0.001). There were no operative mortalities in Group A, and the morbidity rate was comparable with that of Groups B and C. Upon re-evaluation, many tumors (54%) previously deemed "unresectable" were surgically extirpated for cure with a median survival comparable with that of patients who did not undergo previous exploration.

Adenocarcinoma↗
PubMed2000

Surgical treatment of metastatic pulmonary soft-tissue sarcoma.

The lung is the most frequent site of metastasis from soft-tissue sarcomas. Due to the relative resistance of sarcoma to either chemotherapy or radiotherapy, compared to other solid tumors, surgical management of pulmonary metastases has been a pivotal therapy in this disease. With decades of experience in numerous centers, criteria for patient selection have been ascertained and documented. We review the current literature on the use of pulmonary metastasectomy in patients with soft-tissue sarcoma, as well as survival data after such treatment. Osteogenic sarcoma is not included in this discussion.

Biomarkers, Tumor↗
PubMed1999

[Clinical analysis of 17 patients with adrenal "incidentaloma"].

This paper reports 17 cases of adrenal "incidentaloma", discovered by B-mode ultrasonography, computed tomography and/or magnetic resonance imaging scan and identified by operation and pathological examination. Seven of them were pathologically diagnosed as adrenocortical adenoma, 4 pheochromocytoma, 2 adrenal cyst, and 1 mixed cell adenoma, 1 leiomyoma, 1 adrenocortical carcinoma, and 1 gangliocytoma. Adrenal shows hormone-secreting function in 17 patients with adrenal "incidentaloma". The diagnosis and management of this disorder are discussed.

Adenoma↗
PubMed1998

Irradiation in carcinoma of the vulva: factors affecting outcome.

PURPOSE: This report reviews the increasing role of radiation therapy in the management of patients with histologically confirmed vulvar carcinoma, based on a retrospective analysis of 68 patients with primary disease (2 in situ and 66 invasive) and 18 patients with recurrent tumor treated with irradiation alone or combined with surgery. METHODS AND MATERIALS: Of the patients with primary tumors, 14 were treated with wide local excision plus irradiation, 19 received irradiation alone after biopsy, 24 were treated with radical vulvectomy followed by irradiation to the operative fields and inguinal-femoral/pelvic lymph nodes, and 11 received postoperative irradiation after partial or simple vulvectomy. The 18 patients with recurrent tumors were treated with irradiation alone. Indications and techniques of irradiation are discussed in detail. RESULTS: In patients treated with biopsy/local excision and irradiation, local tumor control was 92% to 100% in Stages T1-3N0, 40% in similar stages with N1-3, and 27% in recurrent tumors. In patients treated with partial/radical vulvectomy and irradiation, primary tumor control was 90% in patients with T1-3 tumors and any nodal stage, 33% in patients with any T stage and N3 lymph nodes, and 66% with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for T1N0, 62% for T2-3N0, 30% for T1-3N1 disease, and 11 % for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 tumors. Four of 18 patients (22%) treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and irradiation. In patients with T1-2 tumors treated with biopsy/wide tumor excision and irradiation with doses under 50 Gy, local tumor control was 75% (3 of 4), in contrast to 100% (13 of 13) with 50.1 to 65 Gy. In patients with T3-4 tumors treated with local wide excision and irradiation, tumor control was 0% with doses below 50 Gy (3 patients) and 63% (7 of 11) with 50.1 to 65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and irradiation, local tumor control was 83% (14 of 17), regardless of dose level, and in T3-4 tumors, it was 62% (5 of 8) with 50 to 60 Gy and 80% (8 of 10) with doses higher than 60 Gy. The differences are not statistically significant. There was no significant dose response for tumor control in the inguinal-femoral lymph nodes; doses of 50 Gy were adequate for elective treatment of nonpalpable lymph nodes, and 60 to 70 Gy controlled tumor growth in 75% to 80% of patients with N2-3 nodes when administered postoperatively after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess. CONCLUSIONS: Irradiation is playing a greater role in the management of patients with carcinoma of the vulva; combined with wide local tumor excision or used alone in T1-2 tumors, it is an alternative treatment to radical vulvectomy, with significantly less morbidity. Postradical vulvectomy irradiation in locally advanced tumors improves tumor control at the primary site and the regional lymphatics in comparison with reports of surgery alone.

Adenocarcinoma↗
PubMed1998

Central delivery of human tissue kallikrein gene reduces blood pressure in hypertensive rats.

The human tissue kallikrein gene, in the form of naked DNA (CMV-cHK) or an adenoviral vector (Ad.CMV-cHK), was directly delivered by intracerebroventricular injection into spontaneously hypertensive rats. Control rats received the same amount of vector DNA (pcDNA3) or adenoviral vector (Ad.CMV-LacZ) carrying the lacZ gene. A single injection of the human tissue kallikrein gene caused a rapid and prolonged blood pressure-lowering effect that began 1 day post injection and the effect lasted for more than 7 days. The expression of human tissue kallikrein and its mRNA was identified in the cortex, cerebellum, brain stem, hippocampus and hypothalamus. Cellular localization of beta-galactosidase was detected by X-gal staining in the thalamus, hypothalamus and third ventricle in rats injected with Ad.CMV-LacZ. This suggests that the tissue kallikrein-kinin system may function in the central control of blood pressure homeostasis.

Adenoviridae↗
PubMed1997

Expression of human tissue kallikrein in rat salivary glands and its secretion into circulation following adenovirus-mediated gene transfer.

Replication-deficient adenovirus Ad.CMV-cHK, expressing human tissue kallikrein under the control of the cytomegalovirus enhancer/promoter, was introduced into rat salivary glands via a direct intracapsular injection. A single injection of Ad.CMV-cHK at a dose of 4 x 10(9) pfu resulted in a sustained expression of human tissue kallikrein in rat salivary glands. The level of immunoreactive human tissue kallikrein in rat sera was the highest at 1 day post gene delivery when both salivary glands were injected and decreased in a time-dependent manner after gene delivery. Human tissue kallikrein levels in sera increased concomitantly with the amount of adenovirus used in direct salivary injection. The detection of human tissue kallikrein in sera after gene delivery into salivary glands provided direct evidence indicating that rat salivary glands secrete locally synthesized human tissue kallikrein to the systemic circulation. The direct injection of salivary glands with replication-deficient adenovirus could provide a systemic route for gene delivery for studying salivary gland function and development. Targeted gene delivery to the salivary gland may provide the means to express therapeutic proteins in saliva and the systemic circulation.

Adenoviridae↗
PubMed1997

Effect of cyclosporin A on the expression of tissue kallikrein, kininogen, and bradykinin receptor in rat.

The tissue kallikrein-kinin system is involved in vasodilation and blood pressure regulation. In the present study, we investigated the effects of chronic cyclosporin A (CsA) administration on blood pressure and the expression of tissue kallikrein, kininogen, and bradykinin receptor in normotensive Wistar rats. Chronic administration of CsA significantly increased systolic blood pressure compared with control rats (n = 6, P < 0.01), although body weight was significantly lower than control rats (n = 6, P < 0.01). The development of hypertension was accompanied by the altered expression of kallikrein-kinin system components. Immunoreactive renal kallikrein and urinary excretion of tissue kallikrein levels were increased by chronic administration of CsA (n = 5 or 6, P < 0.05). Levels of N-tosyl-L-phenylalanine chloromethyl ketone-trypsin and kallikrein-releasable kininogens in sera increased in response to chronic CsA treatment (n = 5 or 6, P < 0.05). Chronic CsA treatment significantly increased renal kallikrein, bradykinin B2 receptor, and hepatic kininogen mRNA levels. The increased levels of tissue kallikrein-kinin system components were accompanied by significant increases in 24-h urine excretion and water intake after chronic CsA treatment (n = 5, P < 0.05). These results suggest that enhanced activity of the tissue kallikrein-kinin system may compensate for the CsA-induced vasoconstriction and hypertension.

Animals↗
PubMed1997

[Evaluation of optimal measuring site and index by QDR4500A for postmenopausal bone loss].

As the function of most bone mineral measuring machine is limited, either by single photon absorptiometry (SPA), dual photon absorptiometry (DPA), speed of sound (SOS), or dual energy x-ray absorptiometry (DEXA), it is hard to evaluate the best place and index of postmenopausal bone loss at many positions by one machine at the same time. So we used QDR4500A, one of the best advanced DEXA which has a good repeatability, to search the best place and index for postmenopausal bone loss. The results showed that (1) bone mineral density (BMD) was better than bone mineral content (BMC) and Area to reflect this kind of bone loss; (2) lumber BMD was a better place than the forearm BMD, total spine BMD and other places; and (3) midlateral L3, 4 BMD was a best index for postmenopausal bone loss.

Absorptiometry, Photon↗
PubMed1997

[Pre- and post-operative changes in serum levels of glycocholic acid and 3,5,3'-triiodothyronine and their clinical significance in patients with cholelithiasis].

Pre- and post-operative changes of serum glycine-conjugated cholic acid (CG) and 3,5,3'-triiodothyronine (T3) levels were observed in twenty-two patients with cholelithiasis. The increase of the levels of serum CG varied with the patients; the highest levels were seen in patients with cirrhosis. After operation, the levels of serum CG and T3 were decreased significantly in patients without cirrhosis. There was positive correlation between serum CG and T3 (r = 0.4667, P < 0.01). It is indicated that the lowering of serum CG after operation may be related to the lowering of serum T3; the significant increase of serum CG level is useful to the diagnosis of liver cirrhosis, which is more sensitive than Type B ultrasonography or routine examination of liver function.

Adult↗
PubMed1996

A function for the integrin alpha6beta4 in the invasive properties of colorectal carcinoma cells.

Expression of the integrin alpha6beta4, a receptor for the laminin family of matrix proteins, has been correlated with the progression and metastatic potential of several different tumors, including colorectal carcinoma. For this reason, defining the mechanistic contribution of alpha6beta4 to the aggressive behavior of colorectal and other carcinoma cells is an issue of timely importance for cancer biology. In the present study, we sought to gain insight into the function of alpha6beta4 in colorectal carcinoma cells by studying the behavior of clone A cells, which express high surface levels of this integrin, and by restoring alpha6beta4 expression in RKO cells, a beta4-deficient rectal carcinoma cell line. The data obtained reveal that alpha6beta4 expression increases the adhesive strength of these cells on laminin-1 matrices, although it does not increase their ability to migrate on such matrices. The RKO/beta4 transfectants were considerably more spread on Matrigel, laminin-1, and collagen I than the mock transfectants and displayed numerous extensions suggestive of pseudopodia. More importantly, we discovered that expression of alpha6beta4 facilitates the ability of colorectal carcinoma cells to invade both Matrigel and collagen I matrices. The alpha6beta4-dependent increases in adhesion and invasion, as well as the observed morphological changes, required an intact beta4 cytoplasmic domain. These data argue for a ligand-independent role for alpha6beta4 in promoting cell invasion, and they have important implications for the involvement of this integrin in colorectal carcinoma progression.

Antigens, Neoplasm↗
PubMed1996

Function of the integrin alpha 6 beta 1 in metastatic breast carcinoma cells assessed by expression of a dominant-negative receptor.

The involvement of the alpha 6 beta a integrin, a laminin receptor, in breast carcinoma progression needs to be addressed rigorously. We report that a human breast carcinoma cell line, MDA-MB-435, known to be highly invasive and metastatic, expresses three potential integrin laminin receptors: alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1, but uses only alpha 6 beta 1 to mediate adhesion and migration on laminin matrices. To investigate the contribution of alpha 6 beta 1 to the aggressive behavior of these cells, we developed a dominant-negative strategy for knocking out alpha 6 beta 1 function that involved expression of a cytoplasmic domain deletion mutant of the beta 4 integrin subunit by cDNA transfection. Stable transfectants of MDA-MB-435 cells that expressed this mutant beta 4 subunit were inhibited dramatically in their ability to adhere and migrate on laminin matrices, and their capacity to invade Matrigel was reduced significantly. These findings support the hypothesis that alpha 6 beta 1 is important for breast cancer progression. Moreover, this approach is a powerful method that should be useful in assessing the role of alpha 6 beta 1 in other cells.

Breast Neoplasms↗
PubMed1996

Differential regulation of kallikrein, kininogen, and kallikrein-binding protein in arterial hypertensive rats.

This study was designed to determine whether the kallikrein-kinin system exerts a protective action in hypertension induced by chronic inhibition of nitric oxide synthase. N omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/100 ml water) was given orally to Sprague-Dawley rats, while controls received regular tap water. Hepatic kininogen mRNA levels in the L-NAME-treated group were 2.9- and 2.5-fold higher at 3 and 4 wk, respectively, compared with control rats, whereas kallikrein-binding protein (KBP) mRNA levels were 82% and 45% of the values found in control rats at 3 and 4 wk, respectively. There was no significant change in hepatic alpha 1-antitrypsin mRNA levels under the same conditions. At 3 and 4 wk post L-NAME treatment, renal kallikrein mRNA levels were 2.5- and 3.4-fold higher than in controls, whereas renal beta-actin mRNA levels were similar between groups. Changes in the transcript levels of renal kallikrein, kininogen, and KBP were consistent with their protein levels. Immunoreactive total kininogen and low-Mr kininogen levels in sera and tissue kallikrein levels in kidney were significantly higher in the L-NAME-treated group, whereas KBP levels in the circulation were lower compared with controls. Systolic blood pressure was increased by 58 +/- 4 mmHg after 4 wk of L-NAME treatment. This effect was enhanced in rats given L-NAME in combination with HOE-140, a bradykinin B2-receptor antagonist, at the dose of 100 micrograms/day ip (79 +/- 5 vs. 58 +/- 4 mmHg, P < 0.05). This difference was confirmed by direct measurement of mean blood pressure (MBP). An intra-arterial bolus injection of 200 ng bradykinin significantly decreased MBP of L-NAME-treated rats, and this effect was blunted in the group treated with the bradykinin antagonist (-29 +/- 3 vs. -9 +/- 2 mmHg, P < 0.01). These results suggest that enhanced kallikrein and kininogen synthesis may have a protective role against the cardiovascular effects induced by chronic inhibition of nitric oxide synthesis.

Animals↗
PubMed1996

High-salt diet upregulates kininogen and downregulates tissue kallikrein expression in Dahl-SS and SHR rats.

Tissue kallikrein cleaves low-molecular-weight (low-M(r)) kininogen to produce the vasoactive kinin peptide. It has been suggested that hypertensive patients with low urinary kallikrein excretion may have a defect in sodium handling. In this study, we examined the effect of a high-salt diet on the expression of tissue kallikrein and kininogen genes in Dahl salt-sensitive rats (Dahl-SS), spontaneously hypertensive rats (SHR), and normotensive Sprague-Dawley rats (SD) by Northern and Western blot analysis and radioimmunoassay. Control and experimental groups received normal and high-salt diets containing 0.4% and 8% NaCl, respectively, for 6 wk. High-salt diet induced a significant time-dependent increase of blood pressure in both strains of hypertensive rats and a slight but significant increase of blood pressure in normotensive SD rats. Hepatic kininogen mRNA levels of both Dahl-SS and SHR on a high-salt diet increased 2.4-fold and 2.0-fold, respectively, while alpha 1-antitrypsin mRNA levels were not changed in rats receiving high-salt diet. Immunoreactive total kininogen and low-M(r) kininogen (58 kDa) levels in sera increased in response to high-salt diet in both strains of hypertensive rats. In SD rats, the low-M(r) kininogen level in sera was unaltered, whereas total kininogen increased in response to high-salt diet. Tissue kallikrein mRNAs in the kidney and salivary glands of Dahl-SS, SHR, and SD rats were reduced, whereas beta-actin mRNA was not altered by high-salt diet. Similarly, immunoreactive intrarenal kallikrein levels were reduced in these rats in response to high-salt diet. These studies show that increases in blood pressure after salt loading in Dahl-SS and SHR are accompanied by increases in low-M(r) kininogen. Tissue kallikrein gene expression in hypertensive Dahl-SS and SHR and normotensive SD rats is suppressed after salt loading. These findings show that reduced renal kallikrein expression and increased kininogen expression is regulated at the transcriptional level during salt loading.

Animals↗