Biomedical subjects

S E Sen

Publications and source records attributed to S E Sen.

12 recordsLinked to original sources

PubMed2003

Juvenile hormone biosynthesis in moths: synthesis and evaluation of farnesol homologs as alternate substrates of farnesol oxidase.

The oxidation of farnesol to farnesal is an important step in insect juvenile hormone (JH) biosynthesis and is mediated by one or more alcohol oxidases located within the minute endocrine gland, the corpus allatum. Because lepidopteran insects have the capacity to produce homologous JH structures, the substrate selectivity of farnesol oxidase was examined by determining the ability of several terpenol homologs to inhibit farnesol oxidation in moths. Results utilizing corpora allata homogenates from larval, adult, and embryonic Manduca sexta indicate that increased steric bulk at the C-3 position of the sesquiterpenol chain is detrimental to inhibitory potency. Triethylhomofarnesol (1h), which is precursor to JH 0 and therefore a physiologically important metabolite of M. sexta embryos, was found to be a poor inhibitor of farnesol oxidation but was oxidized in almost same amount as farnesol. This data indicate that farnesol oxidase of the corpus allatum plays a limited role in controlling JH homolog production in moths, and suggests that another oxidative enzyme, which is present at early stages of moth development, is involved in JH homolog construction.

Alcohol Oxidoreductases↗

PubMed2001

Farnesol oxidation in insects: evidence that the biosynthesis of insect juvenile hormone is mediated by a specific alcohol oxidase.

The oxidation of farnesol to farnesoic acid is a key step in insect juvenile hormone biosynthesis. We herein present preliminary characterization of the enzyme-catalyzed oxidation of farnesol to farnesal in larval corpora allata homogenates of the tobacco hornworm, Manduca sexta. This conversion, which is highly substrate specific, has a K(m) apparent of 1 microM and a pH optimum between 6 and 7. Results from chemical modification experiments indicate that the enzyme possesses an active site tyrosine residue. Although farnesol oxidation in adult M. sexta corpora allata homogenates was previously identified as being catalyzed by a dehydrogenase, the corresponding conversion in larvae is not effected by the addition of nicotinamide cofactors. Instead, enzymatic activity is slightly enhanced by the addition of FAD, decreases when incubations are performed anaerobically, and is completely inhibited when either sodium dithionite or glucose oxidase is added. Although the effect of various additives suggests that the oxidation of farnesol to farnesal does not require a metal redox center, 1,10-phenanthroline (but not 4,7-phenanthroline) is a weak irreversible inhibitor of farnesol oxidation (IC(50)=11 mM). The addition of exogenous metals (Fe2+, Cu2+, Ni2+, and Co2+) caused differential effects on farnesol metabolism, with Cu2+ being highly inhibitory. Taken together, this data suggests that the oxidation of farnesol to farnesal in larval corpora allata is mediated by a specific oxygen-dependent enzyme, perhaps a flavin and/or iron-dependent oxidase.

Alcohol Oxidoreductases↗

PubMed1999

Characterization of the Saccharomyces cerevisiae ERG27 gene encoding the 3-keto reductase involved in C-4 sterol demethylation.

The last unidentified gene encoding an enzyme involved in ergosterol biosynthesis in Saccharomyces cerevisiae has been cloned. This gene, designated ERG27, encodes the 3-keto sterol reductase, which, in concert with the C-4 sterol methyloxidase (ERG25) and the C-3 sterol dehydrogenase (ERG26), catalyzes the sequential removal of the two methyl groups at the sterol C-4 position. We developed a strategy to isolate a mutant deficient in converting 3-keto to 3-hydroxy-sterols. An ergosterol auxotroph unable to synthesize sterol or grow without sterol supplementation was mutagenized. Colonies were then selected that were nystatin-resistant in the presence of 3-ketoergostadiene and cholesterol. A new ergosterol auxotroph unable to grow on 3-ketosterols without the addition of cholesterol was isolated. The gene (YLR100w) was identified by complementation. Segregants containing the YLR100w disruption failed to grow on various types of 3-keto sterol substrates. Surprisingly, when erg27 was grown on cholesterol- or ergosterol-supplemented media, the endogenous compounds that accumulated were noncyclic sterol intermediates (squalene, squalene epoxide, and squalene dioxide), and there was little or no accumulation of lanosterol or 3-ketosterols. Feeding experiments in which erg27 strains were supplemented with lanosterol (an upstream intermediate of the C-4 demethylation process) and cholesterol (an end-product sterol) demonstrated accumulation of four types of 3-keto sterols identified by GC/MS and chromatographic properties: 4-methyl-zymosterone, zymosterone, 4-methyl-fecosterone, and ergosta-7,24 (28)-dien-3-one. In addition, a fifth intermediate was isolated and identified by (1)H NMR as a 4-methyl-24, 25-epoxy-cholesta-7-en-3-one. Implications of these results are discussed.

Amino Acid Sequence↗

PubMed1997

Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol.

Fruits and vegetables have protective effects against many human cancers, including pancreatic cancer. Isoprenoids are one class of phytochemicals which have antitumor activity, but little is known about their effects on cancer of the pancreas. We tested the hypothesis that isoprenoids would inhibit the growth of pancreatic tumor cells. Significant (60-90%) inhibition of the anchorage-independent growth of human MIA PaCa2 pancreatic tumor cells was attained with 25 microM farnesol, 25 microM geranylgeraniol, 100 microM perillyl amine, 100 microM geraniol, or 300 microM perillyl alcohol. We then tested the relative in vivo antitumor activities of dietary farnesol, geraniol, and perillyl alcohol against transplanted PC-1 hamster pancreatic adenocarcinomas. Syrian Golden hamsters fed geraniol or farnesol at 20 g/kg diet exhibited complete inhibition of PC-1 pancreatic tumor growth. Both farnesol and geraniol were more potent than perillyl alcohol, which inhibited tumor growth by 50% at 40 g/kg diet. Neither body weights nor plasma cholesterol levels of animals consuming isoprenoid diets were significantly different from those of pair-fed controls. Thus, farnesol, geraniol, and perillyl alcohol suppress pancreatic tumor growth without significantly affecting blood cholesterol levels. These dietary isoprenoids warrant further investigation for pancreatic cancer prevention and treatment.

Acyclic Monoterpenes↗

PubMed1990

Inhibition of vertebrate squalene epoxidase by extended and truncated analogues of trisnorsqualene alcohol.

The epoxidation of squalene to (3S)-2,3-epoxysqualene and subsequent cyclization to lanosterol are keys steps in vertebrate cholesterol biosynthesis. Trisnorsqualene alcohol (TNSA) has previously been reported as a potent inhibitor of vertebrate squalene epoxidase, with IC50 = 4 microM for pig liver (J. Am. Chem. Soc. 1989, 111, 1508-1510). Analogues with extended and truncated carbon skeletons have been prepared and tested for pig liver squalene epoxidase (SE) inhibition. Most of the structural analogues were poor inhibitors of vertebrate SE, with the exception of bisnorsqualene alcohol which had the same activity as TNSA. These results support the theory that an intact trisnorsqualene moiety is required for activity.

Animals↗

PubMed1989

Congenital urethral diverticulum in the male.

Congenital urethral diverticulum is rare in males. We describe a twenty-one-year-old man who had a congenital urethral diverticulum at the bulbous portion of the anterior urethra.

Adult↗

PubMed1989

Renal hydatidosis.

Renal hydatidosis in humans is rare, although it is not uncommon in sheep- and cattle-raising countries. We describe a patient who had renal hydatidosis with hydatidcysturia.

Adult↗

PubMed1989

Squalene analogues containing isopropylidene mimics as potential inhibitors of pig liver squalene epoxidase and oxidosqualene cyclase.

Several squalene analogues containing 1,1-dihaloalkene, acetylene, allene, diene, and cyclopropane functionalities were synthesized and evaluated as potential inhibitors of pig liver squalene epoxidase and oxidosqualene cyclase. Both monofunctionalized and bisfunctionalized analogues were prepared. Poor inhibition of squalene epoxidase and oxidosqualene cyclase was found for most compounds (IC50 much greater than 400 microM), with the exception of the monofunctionalized alkynol (IC50 = 300 microM). This alkynol showed mixed-function inhibition with KI = 0.95 mM. Oxidation of the alcohol to the alkynone resulted in loss of epoxidase activity, indicating that the hydroxyl group is necessary for inhibition and that the alkynol is not a proinhibitor. Molecular mechanics calculations indicated that a good inhibitor should possess hydrophobic substituents on an unpolarized, unsaturated system; additionally, the presence of a pro-C-3 hydroxyl group can confer inhibitory potency.

Alkenes↗

PubMed1988

Experience with extracorporeal surgery and autotransplantation for renal cell and transitional cell cancer of the kidney.

Of 21 patients who underwent bench surgery for renal malignancies (renal cell carcinoma in 16 and transitional cell carcinoma in 5) 15 also had autotransplantation and 6 did not. In 5 patients the contralateral kidney was removed simultaneously for synchronous bilateral renal malignancy, and 16 had cancer in a solitary kidney. In the 3 patients who underwent nephrectomy for complications after autotransplantation no evidence of residual tumor was noted on histopathological examination. Of 9 patients 1 (11 per cent) had local recurrence after successful autotransplantation (renal cell carcinoma). Two patients with transitional cell carcinoma died of metastatic disease. Treatment failed in 31 per cent of the 16 patients with renal cell carcinoma (metastatic disease in 4 and metastatic disease with local recurrence in 1). Removal of solitary or synchronous bilateral renal cell cancer by bench surgery with subsequent autotransplantation is effective. For high grade transitional cell carcinoma of a solitary kidney its value is doubtful without adjuvant systemic treatment.

Adult↗

PubMed1988

Neoadjuvant chemotherapy for locally advanced transitional cell carcinoma of the bladder: do local findings suggest a potential for salvage of the bladder?

Sixteen patients with locally advanced transitional cell carcinoma of the bladder were given two to four cycles of combination chemotherapy with methotrexate, vinblastine, doxorubicin hydrochloride (Adriamycin), and cisplatin (M-VAC) in an effort to reduce tumor size and enhance the potential for surgical resection. All patients had initial clinical staging (based on cystoscopy and cystoscopic biopsy, urine cytology, computed tomographic scanning, and excretory urography). Before each cycle, all patients had repeat clinical staging tests. Ten patients underwent postchemotherapy bilateral pelvic lymphadenectomy and radical cystoprostatectomy, and their bladders were examined histopathologically by step-sectioning techniques. One patient underwent abdominal exploration, bilateral pelvic lymphadenectomy, and ipsilateral partial cystectomy. Five patients had repeat clinical staging only without removal of their bladders. Of the 16 patients, 5 (31%) had residual invasive tumor and no tumor response. Three patients (19%) had a partial response, two of whom had only carcinoma in situ (one with prostatic duct involvement) and one of whom had stage pT1, NO, MO disease. Five patients (31%) had normal findings on computed tomographic scans, cystoscopy, biopsy, and urine cytology and thus had complete responses. In addition, 3 of 11 patients who underwent pathologic staging had no residual tumor on clinical and surgical staging and were complete responders. The overall (partial + complete) response rate was 69%, and the overall complete remission rate (pathologic + clinical staging) was 50%. These results suggest that the concept of possible salvage of the bladder with the current treatment program might be premature and must be applied selectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1986

Significance of serum protein and lipid-bound sialic acid as a marker for genitourinary malignancies.

A prospective study was done to evaluate the roles of serum N-acetylneuraminic acid (NANA) and the lipid-bound subfraction of sialic acid (LSA) concentrations in the detection and staging of cancer, and the follow-up of treatment in patients with genitourinary malignancies. Multiple determinations were obtained in 177 subjects: 90 normal volunteers, 38 patients with prostate cancer, 20 patients with bladder cancer, 15 patients with renal cell cancer, and 14 patients with benign urologic diseases. The results showed a low incidence of elevated values in patients with early stages of cancer and a high incidence of false-positive values with serum NANA concentrations in patients with benign urologic diseases, especially prostatitis. Serum NANA and LSA concentrations were highly correlated with the stage and grade in patients with advanced urologic cancer, and may be used as markers of tumor activity during follow-up under treatment; currently, however, they are not useful in the screening of patients for urologic cancer. Their usefulness in prostatic cancer is at least comparable to that of acid phosphatase determinations by the enzymatic and radioimmunoassay methods, which were elevated in a smaller percentage of patients with prostate cancer than were the NANA or LSA concentrations.

Adult↗

PubMed1985

Sarcoma and carcinosarcoma of the bladder in adults.

Sarcomas of the bladder occur rarely in adults. As a result, the natural history of these unusual tumors and the best methods of treatment are uncertain. We reviewed our experience with 13 patients presenting between 1970 and 1980 (5 had leiomyosarcoma, 5 had carcinosarcoma and 3 had rhabdomyosarcoma). Gross hematuria nearly always was the presenting symptom. Patients treated by partial cystectomy fared poorly, while 7 treated by radical cystectomy and supravesical urinary diversion had an excellent prognosis: 6 (86 per cent) have been free of disease for more than 1 year, including 4 who have survived more than 45 months without evidence of recurrence or metastasis.

Adult↗