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Biomedical subjects

K N Khan

Publications and source records attributed to K N Khan.

At least 19 recordsLinked to original sources
PubMed2005

Effects of miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/tween 80.

Miglyol 812 is a medium-chain triglyceride used in toxicology studies as an excipient to improve test compound solubility/absorption. As part of a larger toxicology study, 15 Wistar Han IGS rats/sex/group were dosed by oral gavage for 4 weeks with 10 mL kg(-1) day(-1) of 100% Miglyol 812 or 0.5% methylcellulose/0.1% Tween 80 in water (MC-T) followed by 4 weeks without treatment to evaluate the potential effects of this excipient in long-term toxicology studies relative to a traditional excipient such as MC-T. Clinical signs evident during the dosing phase included soft and/or mucoid stool in 12/15 males and 11/15 females treated with Miglyol 812 but in no animals treated with MC-T. Animals treated with Miglyol 812 had a 6-7% statistically significant reduction in body weight gain as compared to MC-T-treated animals. Statistically significant changes in clinical chemistry parameters as compared to MC-T included decreased blood urea nitrogen (50% and 29% in males and females, respectively), increased cholesterol (1.6-fold and 1.5-fold in males and females, respectively), decreased total protein (6% and 8% in males and females, respectively), decreased globulins (15% and 11% in males and females, respectively), and increased triglycerides (2.8-fold and 1.7-fold in males and females, respectively). Absolute and relative thymic weights decreased 28% and 24%, respectively, in males, and 18% and 17%, respectively, in females without histological alterations. Histopathology revealed increased alveolar histiocytosis with focal interstitial inflammation in lungs in 5/10 males and 7/10 females treated with Miglyol 812 compared to only 1/10 males and 1/10 females treated with MC-T. All effects were reversible during the recovery period. Results of this study indicate that 100% miglyol 812 produces reversible gastrointestinal effects and decreases in body weight gains along with changes in several serum chemistry parameters. Therefore, it should not be considered innocuous when delivered by oral gavage in long-term rodent toxicology studies.

Animals↗
PubMed2003

Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice.

BACKGROUND: The inducible cyclooxygenase-2 (COX-2) enzyme is upregulated in inflammatory diseases, as well as in epithelial cancers, and has an established role in angiogenesis and tissue repair. OBJECTIVE: Because of these physiological effects and the widespread use of the selective COX-2 inhibitor, celecoxib, we wanted to determine if inhibition of COX-2 would affect incisional skin wound healing. METHODS: Using a cutaneous full-thickness, sutured, incisional wound model in hairless SKH-1 mice, we evaluated the role of COX-2 in the wound healing process by comparing the effects of a nonselective COX inhibitor, diclofenac, with a selective COX-2 inhibitor, SC-791. Healing was monitored for up to 28 days postincision histologically and for recovery of wound strength. RESULTS: COX-2 expression was observed over the first week of healing, peaking at day 3 and was not affected by treatment with the selective COX-2 or nonselective COX inhibitors. Infiltrating macrophages, as well as keratinocytes and dermal fibroblasts at the wound site, expressed COX-2. Neither selective COX-2, nor nonselective COX inhibition had a significant effect on the macroscopic or microscopic morphology of the wounds, whereas dexamethasone treatment resulted in epidermal and granulation tissue atrophy. In addition, neither selective COX-2, nor nonselective COX inhibition altered keratinocyte proliferation and differentiation, dermal angiogenesis or the recovery of wound tensile strength, whereas dexamethasone reduced the tensile strength of the wounds by 30-38% throughout the healing period. CONCLUSIONS: These data indicate that selective COX-2 inhibition does not affect the healing of surgical skin wounds.

Animals↗
PubMed2001

Localization of cyclooxygenase isozymes in cardiovascular tissues of dogs treated with naproxen.

Prostaglandins have diverse roles in the cardiovascular system mediating both physiologic and inflammatory responses. Two cyclooxygenase isoforms, cyclooxygenase-1 and cyclooxygenase-2, catalyze prostaglandin production. In many tissues and cell types studied, cyclooxygenase-1 is constitutively active whereas cyclooxygenase-2 expression is primarily responsible for prostaglandin production during inflammation. However, little information exists concerning which isoform is responsible for prostaglandin-mediated effects in the heart. We examined cyclooxygenase-1 and cyclooxygenase-2 expression in heart and vascular tissue of dogs using isoform-specific antibodies. In addition, tissues from dogs treated with naproxen (5-10mg/kg/day), an inhibitor of prostaglandin production were also examined. Cyclooxygenase-1 expression was evident in endothelial cells of the microvasculature of the heart, aorta and renal artery. Cyclooxygenase-1 expression was also found in fibrocytes of the tricuspid valve and in the chordae tendinae. Animals treated with naproxen exhibited a similar pattern and intensity of cyclooxygenase-1 staining. No cyclooxygenase-2 expression was evident in cardiac tissue. However, minimal cyclooxygenase-2 immunoreactivity was present in the vascular endothelial cells of small myocardial blood vessels located in several regions of the heart as well as in endothelial cells of the aorta. These data may expand our understanding of the effects of non-steroidal anti-inflammatory drugs on cardiac function.

Animals↗
PubMed2001

Enhanced cyclooxygenase-2 expression in sporadic and familial adenomatous polyposis of the human colon.

BACKGROUND: The cyclooxygenase (COX) enzymes exist in two related but unique isoforms (COX-1 and COX-2) and catalyze the formation of prostaglandins (PGs). COX-1 is constitutively expressed, and is responsible for the synthesis of PGs necessary for gastroprotection and normal renal function. The COX-2 isoform is important in a variety of pathophysiological conditions such as inflammation and tumorigenesis. Numerous studies report that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) can decrease the incidence of some tumor types, including gastrointestinal polyposis. METHODS: In this study, we evaluated COX-1 and COX-2 expression in 30 polyps collected from 10 patients with familial adenomatous polyposis (FAP) and in 18 polyps collected from 18 patients with sporadic adenomatous polyposis (SAP) using COX-1 or COX-2 isoform-specific antibodies. All tissues were formalin-fixed and paraffin-embedded. Immunoreactivity was detected using tyramide signal amplification and evaluated utilizing an immunohistochemical scoring system. RESULTS: COX-2 was minimally detected in the distant non-neoplastic epithelium, which also served as an internal negative control. In comparison, all polyps collected from SAP or FAP patients overexpressed COX-2 in the neoplastic epithelial cells (P < or = 0.002). Additionally, pronounced COX-2 expression was observed in the stromal cells underlying and adjacent to adenomatous lesions. COX-1 immunoreactivity was weak to mild throughout each tissue evaluated and did not change in the neoplastic or stromal cells of the polyps. CONCLUSIONS: COX-2 expression is upregulated in the adenomatous epithelium of SAP and FAP, while the COX-1 isoform appears to be constitutively expressed at low levels in both neoplastic and non-neoplastic regions. The differential expression of COX-1 and COX-2 in these neoplasms suggests that COX-2 rather than COX-1 may play a role in adenoma formation and/or growth in cases of SAP and FAP in humans.

Adenomatous Polyposis Coli↗
PubMed2001

Expression of cyclooxygenase-2 in canine renal cell carcinoma.

Cyclooxygenase-2 (COX-2) has been shown to be the primary enzyme responsible for prostaglandin production during inflammation but is absent in most tissues under normal physiological states. High levels of COX-2 expression have been observed in the macula densa and thick ascending limbs of fetal kidneys; this expression declines to minimal levels during renal maturation. We hypothesized that the neoplastic cells of renal cell carcinoma (RCC) may revert to high expression of COX-2, and we evaluated its expression in three spontaneous cases of canine RCC by using immunohistochemical methods. The neoplastic cells of two of the three cases exhibited moderate to marked COX-2 immunoreactivity. These results suggest that some canine renal cell carcinomas express high levels of COX-2, which may play a role in the modulation of neoplastic cell growth.

Animals↗
PubMed2000

COX-2 is expressed in human pulmonary, colonic, and mammary tumors.

BACKGROUND: The cyclooxygenase (COX) enzyme catalyzes the formation of prostaglandins, which can affect cell proliferation and alter the response of the immune system to malignant cells. The inducible form of COX, COX-2, has been shown to be important in carcinogenesis. METHODS: The authors studied COX-1 and -2 expression in 20 tumors of the lung, colon, and breast (60 total) by using commercially available monoclonal and polyclonal antibodies on formalin fixed, paraffin embedded tissue. Our evaluation also included seven carcinoma-associated colonic adenomas and 10 mammary ductal carcinomas in situ (DCIS). Quantitation of immunoreactivity was accomplished using an immunohistochemical scoring system that approximates the use of image analysis-based systems. RESULTS: Ninety percent of lung tumors (squamous cell carcinomas and adenocarcinomas), 71% of colon adenocarcinomas and 56% of breast tumors (DCIS and infiltrating ductal and lobular carcinomas) expressed COX-2 at a moderate to strong level, which was significantly different from the negligible expression in distant nonneoplastic epithelium (controls; P < 0.0001). Poorly differentiated histologic features were correlated with low COX-2 expression overall, especially in colon carcinomas. Among breast carcinomas, DCIS was more likely to express COX-2 than invasive carcinomas. Adenomatous colonic epithelium showed moderate COX-2 expression, as did adjacent nonneoplastic epithelium. COX-1 immunoreactivity was essentially weak to moderate in all tissues evaluated. CONCLUSIONS: COX-2 expression is upregulated in well and moderately differentiated carcinomas of the lung, colon, and breast whereas COX-1 appears to be constitutively expressed at low levels. A possible COX-2 paracrine effect is suggested by moderate immunoreactivity in adjacent nonneoplastic epithelium.

Breast↗
PubMed2000

Prospective analysis of risk factors for early intrahepatic recurrence of hepatocellular carcinoma following ethanol injection.

BACKGROUND/AIM: Time-dependent intrahepatic recurrence of hepatocellular carcinoma is frequent after different treatment modalities, including percutaneous ethanol injection. We attempted to prospectively analyze the possible risk factors for early intrahepatic recurrence of hepatocellular carcinoma after percutaneous ethanol injection. METHODS: Sixty-five patients with 65 solitary hepatocellular carcinoma nodules < or =6 cm in diameter underwent initial treatment with percutaneous ethanol injection and were examined to ascertain the factors related to recurrence, local and distant, within the liver. A number of clinical and tumor parameters were analyzed. RESULTS: Cumulative overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 15.6% and 45.1%, respectively, irrespective of clinical and tumor parameters. Overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 40% and 67.5%, for tumor > or =3 cm and 7.5% and 37.5%, for tumor <3 cm. Cumulative local recurrence rates at 12 and 24 months were 26.3% and 43.5%, respectively, for tumor > or =3 cm and 11.7% and 18.2%, respectively, for tumor <3 cm. The log-rank test indicated that a tumor size of > or =3 cm and the presence of capsule for a tumor of <3 cm in diameter were significant risk factors for intrahepatic recurrence. A pretreatment serum PIVKA-II level of > or =0.02 AU/ml was the only clinical parameter associated with overall recurrence (p=0.0041) and distant intrahepatic recurrence (p=0.0307). Distant intrahepatic recurrence rates 12 and 24 months after percutaneous ethanol injection were 22.5% and 31.4%, respectively, for PIVKA-II levels of > or =0.02 AU/ml and 8% and 17.8%, for PIVKA-II of <0.02 AU/ml. Cox's proportional hazard model identified that tumor size, tumor capsule and baseline serum PIVKA-II levels were independently related to intrahepatic recurrence. CONCLUSIONS: These data demonstrate that tumor size and peritumoral capsule were associated with overall and local recurrence of hepatocellular carcinoma. Moreover, pretreatment serum levels of PIVKA-II can indicate the risk of early intrahepatic recurrence and may assist in patient selection and appropriate therapy.

Adult↗
PubMed2000

Proposed abdominal sonographic staging to predict severity of liver diseases: analysis with peritoneoscopy and histology.

Abdominal sonography is a routinely used noninvasive modality for screening and treatment of liver diseases. We attempted to establish a morphological sonographic staging to predict the severity of liver diseases with their consequent analysis with morphological staging of peritoneoscopy and histology. In all, 136 patients were enrolled for the final confirmation of disease state by peritoneoscopy and histology preceded by abdominal sonography. All patients were categorized from stage 0 to stage 5, depending on a proposed criterion of sonographic features based on surface pattern of liver and the appearance of internal echogenic bands relating to the irregularity of the liver texture. A digitized computer quantitation of histogram-based standard deviation (SD) values from different stages of sonographic images was analyzed, and their values were justified by correlation with the definite appearance of an internal echogenic band. The association of different sonographic stages with disease progression was also demonstrated by their relation with peritoneoscopy and histology. In all patients, the different sonographic staging results were significantly correlated with hepatic surface features of peritoneoscopic staging (r = 0.939, P < 0.0001) graded from stage 0 to stage 5 and were also correlated with biopsy-proven staging of fibrosis (r = 0.739, P < 0.0001). The greater SD values of histogram-based echo levels, as analyzed from digitized sonographic images of 90 patients, were associated with the appearance of internal echogenic bands (P < 0.0001). Furthermore, the corresponding SDS were significantly correlated with the qualitative staging of sonographic features (r = 0.781, P < 0.0001), peritoneoscopy (r = 0.786, P < 0.0001) and histology (r = 0.779, P < 0.0001). We concluded that our proposed sonographic staging is well correlated with peritoneoscopic and histological staging of liver diseases, with only a small discrepancy, and can be used clinically to demonstrate the ongoing severity of liver diseases.

Abdomen↗
PubMed2000

Loop diuretics inhibit detubulation and vacuolation in amphibian muscle fibres exposed to osmotic shock.

The effect of loop diuretics at concentrations known to influence cellular water entry coupled to Na-K-Cl co-transport, upon the vacuolation and detubulation following osmotic shock, was investigated in amphibian skeletal muscles. These were exposed to a glycerol-Ringer solution (18 min), an isotonic Ca2+/Mg2+ Ringer solution and cooling. Adding bumetanide (1.0 and 2.0 microM) to these solutions sharply reduced the incidence of detubulation, assessed by abolition or otherwise of action potential after-depolarisations, from 93.9 +/- 4.7% (n = 6) to 5.0 +/- 1.1% (n = 4: mean +/- SEM: 2.0 microM bumetanide). It dramatically reduced the number and fraction of muscle volume occupied by tubular vacuoles, measured using confocal microscopy, from 60.3 +/- 4.3% (n = 10) to 9.0 +/- 1.1% (n = 35). The incidence of large horseradish peroxidase-lined tubular vacuoles, viewed using electronmicroscopy, similarly was reduced with 2 microM bumetanide in the glycerol-Ringer solution. Bumetanide acted through cellular volume adjustments early in the detubulation protocol. Thus, it exerted its maximum effect when added to the glycerol-Ringer, rather than the Ca2+/Mg2+ Ringer solution. Furthermore, whereas fibre diameters measured using scanning electron microscopy returned to normal during glycerol treatment relative to those of control fibres left in isotonic Ringer, addition of 2.0 microM bumetanide in the glycerol Ringer left markedly smaller fibre diameters. Finally equipotent concentrations of the chemically distinct loop diuretics. furosemide and ethacrynic acid similarly influenced detubulation. These findings implicate Na-K-Cl co-transport in the water entry into muscle fibres that would be expected following introduction of extracellular glycerol. This might then enable the subsequent Na-K-ATPase dependent water extrusion that produces the tubular distension (vacuolation) and detachment (detubulation) following glycerol withdrawal, phenomena also observed in muscular dystrophy.

Action Potentials↗
PubMed2000

Cyclooxygenase-2 expression in inflammatory lung lesions of nonhuman primates.

Mammalian cells contain two related but unique isoforms of cyclooxygenase (COX-1 and COX-2). COX-1 is expressed constitutively in a majority of tissues and is involved in the production of prostaglandins (PGs) that modulate normal physiologic functions. COX-2 is inducible by various stimuli and is involved in the production of PGs that modulate physiologic events in development, cell growth, and inflammation. With the exception of peribronchial glands and chondrocytes of peribronchial cartilage, COX-2 is not detectable in the normal lung of nonhuman primates. We evaluated COX-2 expression by immunohistochemical methods in the inflammatory lesions of two cynomolgus monkeys (Macaca fascicularis) with acute severe pneumonia. Both monkeys exhibited acute severe bronchopneumonia; histologically, lung lesions were characterized by infiltration of large numbers of neutrophils and fewer macrophages, mild bronchial epithelial hyperplasia, and slight type-2 pneumocyte hyperplasia. In both monkeys, mild to marked COX-2 immunoreactivity was detected within the cytoplasm of macrophages, bronchial epithelial cells, type-2 pneumocytes, and endothelial cells of blood vessels. No COX-2 immunoreactivity was detectable in the neutrophils that constituted >90% of the inflammatory cells. These observations suggest that in acute inflammatory lung lesions in nonhuman primates 1) COX-2 is induced in the bronchial and alveolar epithelial cells, 2) macrophages are the primary inflammatory cells that exhibit COX-2, and 3) neutrophils do not express COX-2.

Acute Disease↗
PubMed2000

Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs.

OBJECTIVE: To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the urinary bladder epithelium of clinically normal dogs and in transitional cell carcinoma cells of dogs. ANIMALS: 21 dogs with transitional cell carcinoma of the urinary bladder and 8 dogs with clinically normal urinary bladders. PROCEDURE: COX-1 and COX-2 were evaluated by use of isoform-specific antibodies with standard immunohistochemical methods. RESULT: COX-1, but not COX-2, was constitutively expressed in normal urinary bladder epithelium; however, COX-2 was expressed in neoplastic epithelium in primary tumors and in metastatic lesions of all 21 dogs and in new proliferating blood vessels in 3 dogs. Also, COX-1 was expressed in the neoplastic cells. CONCLUSIONS AND CLINICAL RELEVANCE: Lack of expression of COX-2 in normal bladder epithelium and its substantial expression in transitional cell carcinoma cells suggest that this isoform may be involved in tumor cell growth. Inhibition of COX-2 is a likely mechanism of the antineoplastic effects of non steroidal antiinflammatory drugs.

Animals↗
PubMed1999

Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder.

Cyclooxygenase (COX)-inhibiting drugs have antitumor activity in canine and rodent models of urinary bladder cancer. Two isoenzymes of COX have been identified, COX-1 and COX-2. The purpose of this study was to characterize COX-1 and COX-2 expression in human invasive transitional cell carcinoma of the urinary bladder by immunohistochemistry and Western blot analysis. COX-2 was not expressed in normal urinary bladder samples but was detected in 25 of 29 (86%) invasive transitional cell carcinomas of the urinary bladder and in 6 of 8 (75%) cases of carcinoma in situ. These results indicate that COX-2 may play a role in bladder cancer in humans and support further study of COX-2 inhibitors as potential antitumor agents in human bladder cancer.

Aged↗
PubMed1999

Use of FDP and F1P aldolase to detect tumorous and nontumorous tissue damage by ethanol injection of hepatocellular carcinoma.

Changes in serum levels of tumor-specific fructose 1,6-diphosphate (FDP) aldolase and nontumor-specific fructose 1-phosphate (F1P) aldolase activities were analyzed in patients with hepatocellular carcinoma (HCC) to detect the damage of tumorous and nontumorous hepatic cells after percutaneous ethanol injection (PEI). Initial PEI was performed in 20 patients containing 22 HCC nodules with a diameter of < or = 4 cm. Changes in serum hepatic enzyme activities were measured before and after repeated PEI. FDP and F1P aldolase levels were measured by substrate-specific enzymatic methods. Pre- and posttreatment alpha-fetoprotein (AFP) levels were determined by radioimmunoassay. The consequent changes in the total nontumorous liver volumes after PEI were also analyzed by follow-up CT scans. Serum levels of FDP aldolase released by ethanol injection were progressively increased (P < 0.0001) until the third PEI and thereafter decreased. In contrast, serum levels of F1P aldolase were continuously elevated even after the third PEI (P < 0.0001). Serum levels of transaminases were also elevated after repeated PEI (P < 0.0001). The FDP/FIP aldolase ratio decreased significantly with increased volume (>20 ml) of injected ethanol (P = 0.01) caused by nontumorous liver damage. The elevation of FDP aldolase was markedly associated with a decrease in serum levels of AFP (P < 0.001), indicating adequate tumor necrosis. The progression of the total nontumor liver atrophy depended on the volume of injected ethanol and correlated significantly with F1P aldolase levels after PEI (P < 0.01) but not with FDP aldolase. These results demonstrated that caution is needed to avoid nontumorous liver damage caused by the large volume of ethanol injection in treating HCC. Measurement of FDP and F1P aldolase activities in serum after PEI is clinically useful to detect the degree of tumorous and nontumorous tissue damage by ethanol.

Aged↗
PubMed1999

Sodium butyrate induces alkaline phosphatase gene expression in human hepatoma cells.

BACKGROUND AND AIMS: Butyrate, a natural product of colonic bacterial flora, has been reported to increase the activities of a number of enzymes, including alkaline phosphatase, (ALP) in several cancer cell lines. However, butyrate-induced ALP gene expression in human hepatoma cells has not been previously demonstrated. In the present study, the effects of sodium butyrate on cell growth and proliferation, cellular activity and expression of ALP gene in human hepatoblastoma-derived HepG2 cells were investigated. METHODS: The HepG2 cells were treated with sodium butyrate (0-1 mmol/L) and the number of viable cells were counted at 24, 48 and 72 h after treatment. A [3H]-thymidine incorporation study was performed at different concentrations of sodium butyrate for 48 h. The cellular activity of ALP in HepG2 cells by sodium butyrate was measured by a substrate-specific enzymatic assay. To elucidate the effects of sodium butyrate on ALP gene expression, a northern blotting experiment employing hybridization with mouse placental ALP cDNA was performed. RESULTS: Cell growth and proliferation were dose-dependently inhibited by sodium butyrate. Cellular ALP activity was significantly increased in HepG2 cells in a time- and dose-dependent fashion by treatment with sodium butyrate and a maximum activity was observed at 48 h. These effects were reversible when sodium butyrate was removed from the culture medium. By northern blot analysis, the level of ALP messenger RNA was dose-dependently elevated by sodium butyrate. CONCLUSION: Butyrate, at a concentration relevant to the normal physiology of the liver, causes augmented expression of ALP mRNA in HepG2 cells. We assume that increased ALP synthesis in HepG2 cells by sodium butyrate results from an enhanced rate of transcription rather than translation of mRNA.

Alkaline Phosphatase↗
PubMed1999

Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition.

UV light is a complete carcinogen, inducing both basal and squamous cell skin cancers. The work described uses the selective COX-2 inhibitor celecoxib to examine the efficacy of COX-2 inhibition in the reduction of UV light-induced skin tumor formation in hairless mice. UVA-340 sun lamps were chosen as a light source that effectively mimics the solar UVA and UVB spectrum. Hairless mice were irradiated for 5 days a week for a total dose of 2.62 J/cm(2). When 90% of the animals had at least one tumor, the mice were divided into two groups so that the tumor number and multiplicity were the same (P < 0.31). Half of the mice were then fed a diet containing 1500 p.p.m. celecoxib. Tumor number, multiplicity and size were then observed for the next 10 weeks. Ninety-five percent of the tumors formed were histopathologically evaluated as squamous cell carcinoma. COX-2 expression and activity were increased in tumors. After 10 weeks, the difference in tumor number and multiplicity in the drug-treated group was 56% of UV controls (P < 0.001). The results show that the orally administered selective COX-2 inhibitor celecoxib prevents new tumor formation after the onset of photocarcinogenesis and suggest that treatment with celecoxib may be very useful in preventing UV-induced skin tumors in humans.

Animals↗
PubMed1999

Immunohistochemical study of angiogenic factors in endometrium and endometriosis.

The proliferative activity and angiogenic factors of pelvic endometriosis and uterine endometrium and their correlation with different pigmented lesions are important throughout the menstrual cycle. The proliferative activity and/or expression of angiogenic factors appears to be different between endometrium and endometriosis, and also different in each pigmented lesion. Immunohistochemical studies using computerized image analysis have shown that in normal endometrium, the PCNA index shows cyclic variation, but no cyclic change is observed in endometriosis. In the pelvic peritoneum, the PCNA index is higher in red lesions compared to black and white lesions. There is no difference in VEGF expression among different pigmented lesions. However, a cyclic variation of VEGF concentration was found in the peritoneal fluid of patients with endometriosis. As a newly determined angiogenic factor, the number of endoglin-positive cells and the mean endothelial area were higher in red lesions than in black or white lesions. These results suggest that the pathogenesis and activity of endometriosis possibly depends on internal angiogenesis. The cellular activity of endometriotic lesions may not necessarily coincide with the regulation of angiogenesis, and may not be synchronized in each pigmented pelvic lesion of endometriosis. Copyrightz1999S.KargerAG, Basel

Adult↗
PubMed1998

Use of fructose 1,6-diphosphate aldolase to detect tumour necrosis after transcatheter arterial embolization of hepatocellular carcinoma.

Transcatheter arterial embolization (TAE) is a popular and well-established devascularization treatment modality for hepatocellular carcinoma (HCC). The persistent retention of lipiodol on follow-up computed tomography (CT) scan and time-dependent decrease in size of the lipiodol-stained area of tumour after TAE does not reveal the biological death of tumour cells. Moreover, it is difficult to clinically evaluate the effective necrosis of tumour cells by TAE in cases of HCC that do not produce alpha-fetoprotein (AFP). We therefore studied the release of a relatively tumour-specific protein by the necrotic hepatoma cells to evaluate the effectiveness of TAE. Transcatheter arterial embolization was performed in 17 patients with the imaging diagnosis of HCC; either superselective (n = 6) or non-superselective (n = 11) techniques were used. We measured serum levels of relatively tumour-specific fructose 1,6-diphosphate (FDP) aldolase and non-tumour-specific fructose 1-phosphate (F1P) aldolase by substrate-specific enzymatic methods. Enzyme activities were performed before and after TAE. The time-dependent decrease in size of the lipiodol-stained areas was studied on follow-up CT scans after TAE. Pre- and post-treatment serum AFP levels were determined by radio-immunoassay. The six cases of superselective TAE underwent marked tumour regression by CT compared with the 11 cases of non-superselective TAE. Fructase 1,6-diphosphate aldolase output correlated well with post-necrotic tumour regression after TAE (r = 0.87, P= 0.001). The elevation of serum FDP aldolase was also significantly associated with a decrease in serum AFP (r = 0.72, P < 0.01). In contrast, serum F1P aldolase output was inversely correlated with either tumour regression or serum AFP concentrations after TAE. The serum levels of the tumour-specific enzyme FDP aldolase correlated significantly with effective tumour necrosis and consequent tumour regression after TAE. We suggest that measurement of FDP aldolase activity in serum after TAE can be used clinically to detect the degree of tumour necrosis by TAE.

Adult↗