Biomedical subjects

T Böttger

Publications and source records attributed to T Böttger.

At least 19 recordsLinked to original sources

PubMed2004

[Laparoscopic blunt esophageal dissection with abdominal and mediastinal lymph node dissection in Barrett carcinoma].

Esophageal resection has still a high morbidity and mortality. Minimal-invasive procedures don't have such complications. We describe a case of a patient with a Barrett-Carcinoma who was operated on by laparoscopic blunt esophageal dissection with abdominal and mediastinal lymph node dissection (tumor stage: pT3pN1 (2/16) G2). The postoperative course was without any complications.

Adenocarcinoma↗

PubMed2002

Permissive and suppressive effects of dexamethasone on enzyme induction in hepatocyte co-cultures.

1. Steroids are known to act as permissive factors in hepatocytes. This study shows that dexamethasone (DEX) is a permissive factor for induction of CYP2B1/2, CYP3A1, CYP2A1 and probably also CYP2C11 in cultures with primary rat hepatocytes. 2. The induction factor of phenobarbital (PB)-induced formation of 16beta-hydroxytestosterone (OHT), a testosterone biotransformation product predominantly formed by CYP2B1, is increased 18-fold by the addition of 32 nM DEX to the culture medium. Interestingly, higher concentrations of DEX up to 1000 nM led to a concentration-dependent maximally 5-fold decrease (p = 0.002) of phenobarbital-induced 16beta-OHT formation compared with the effect observed with 32 nM DEX. Thus, DEX shows permissive and suppressive effects on enzyme induction depending on the concentration of the glucocorticoid. 3. Qualitatively similar but smaller permissive and suppressive effects of DEX were observed for PB-induced CYP3A1 activity as evidenced by formation of 2beta-, 6beta- and 15beta-OHT. 4. DEX is a permissive factor for induction of CYP2A1 activity by 3-methylcholanthrene (3MC), as evidenced by the formation of 7alpha-OHT. Without addition of DEX, 3MC did not induce formation of 7alpha-OHT, whereas an almost 3-fold induction occurred in the presence of DEX. In contrast to CYP2B and CYP3A, concentrations up to 1000 nM DEX were not suppressive for the induction of CYP2A1. 5. We described recently a technique that allows preparation of cultures from cryopreserved hepatocytes. An almost identical influence of dexamethasone on enzyme induction was observed here in cultures from cryopreserved compared with freshly isolated hepatocytes. 6. Cultures with primary hepatocyte cultures represent a well-established technique for the study of drug-drug interactions. However, a large interlaboratory variation is known. Our study provides evidence that differences in glucocorticoid concentration in the culture medium contribute to this variation.

Animals↗

PubMed2001

[Surgical treatment and outcome in insulinoma].

In the therapy of organic hyperinsulinism, interest is mainly focussed on the surgical removal of the hyperactive tissue. In spite of these progresses, the surgical treatment is not devoid of problems. These comprise the primary untraceable insulinoma, multiple insulinomas, nesidioblastosis and reoperation. The development of laparoscopic surgery leads to new opportunities the rating of which must be defined. Solitary adenomas are causal for primary hyperinsulinism in 80% to 90% of cases. Intraoperative 87.5% of the tumors are palpable and 83% are detectable by ultrasound. By combination of both methods it is possible to remove 97% of the solitary tumors. Occult adenomas, which cannot be represented by preoperative imaging diagnostics are detectable through intraoperative methods in over 80% of cases by palpation or ultrasound respectively. By combination of both methods, 97% of these occult adenomas can be removed. This reliability of the intraoperative detection makes the preoperative localizing diagnostics unnecessary if no MEN-syndrome is present. If a MEN-syndrome is present, multiple adenomas are common. In 60% of cases multiple adenomas are responsible for the persistency of the syndrome after an unsuccessful primary operation. Therefore a preoperative localizing diagnostics is advisable in case of a MEN-syndrome. Multiple adenomas are treated by left-pancreatic resection with enucleation of remaining adenomas in the pancreatic head region. In case of an untraceable adenoma, the possibility of the rare nesidioblastosis should be considered. This rare occurrence can be detected by fresh frozen sectioning. The resection of 75% to 80% of the pancreas is recommended. The attempt of a laparoscopic removal of solitary adenomas may be indicated, taking into account all contraindications. The preliminary requisite for this is an experienced center in endocrine surgery as well as an experienced laparoscopic surgeon. Contraindications for the laparoscopic procedure are: a tumor localized in the head of the pancreas or in the dorsal parts of the organ, multiple adenomas and nesidioblastosis. In case of occult adenomas, laparoscopic therapy is problematic, as they are also difficult to detect intraoperatively through laparoscopy. The incidence of postoperative complications is still high with 30% and a mortality of 2%. Most often pancreatic fistulas (10%) and septic complications were seen.

Adult↗

PubMed2001

[Surgical therapy of carcinoid tumors of the gastrointestinal tract].

More than 70% of all carcinoids are localized in the gastrointestinal tract. Carcinoids of the upper, middle and lower intestines have to be distinguished ontogenetically. The classification according to Capella takes into account the size of the tumor (< 0.9 cm; 1-2 cm; > 2 cm), the grade of invasion of other structures, the grade of angioinvasion, the biologic behaviour, the grade of differentiation and the hormonal activity of the tumor. A carcinoid-syndrome is rarely found. Carcinoids of the small intestine occur multiple in 30-50% and in 20-30% a second malignant tumor is seen. In carcinoids of the colon this percentage is even higher (25-40%). The therapy of carcinoids depends on the size of the tumor and consecutively on the risk of metastasis. A local excision or non-oncologic radical operative procedure is justified in carcinoids smaller than 1 cm. In tumors 1-2 cm in size an individual decision has to be made. Larger tumors should be operated according to oncologic standards. Palliative resections, even of the liver, may be indicated to relieve the symptoms of a carcinoid-syndrome or, to prevent ileus or bleeding in the gastrointestinal tract. The prognosis of gastrointestinal carcinoids is heterogenous: The five-year-survival-rate of appendix-carcinoids is 85.9% over all stages. In rectal carcinoids this rate amounts to 72.2%, in carcinoids of the small intestines to 55.4% and in colon-carcinoids to 41.6%. Carcinoids of the stomach have a five-year-survival-rate of 64.3% in the absence of metastases. Within carcinoids of the stomach type III-tumors have the worst prognosis with a median survival time of 6.5 months.

Carcinoid Tumor↗

PubMed2001

[Hereditary pancreatitis - a clinically relevant cause of pancreatic adenocarcinoma?].

UNLABELLED: Hereditary pancreatitis is an autosomal dominant disease. Recently, the genetic defect has been mapped to chromosome 7q35 and consists mainly of a point mutation in exon 3 of the cationic trypsinogen gene which causes an Arg(CGC)-His(CAC) substitution at residue 117. In patients with hereditary pancreatitis the estimated cumulative risk for pancreatic carcinoma to age 70 approaches 40 %. Thus, the role of hereditary pancreatitis in the pathogenesis of pancreatic carcinoma is of interest. PATIENTS AND METHODS: DNA was extracted from peripheral blood (n = 16), fresh tumor tissue (n = 29) and formalin fixed and paraffin embedded tumor tissue (n = 5) of 50 patients with ductal adenocarcinoma of the pancreas. We specifically amplified exon 3 and the intronic flanking sequences of the cationic trypsinogen gene by nested PCR and performed restriction fragment length polymorphism analysis using the restriction enzyme Afl III. In patients with hereditary pancreatitis the G : A point mutation creates a recognition site for Afl III which is not present in unaffected individuals. RESULTS: None of the 50 patients with ductal adenocarcinoma of the pancreas revealed the G : A point mutation in exon 3 of the cationic trypsinogen gene which is characteristic of hereditary pancreatitis. In addition sequencing of exon 3 did not reveal any other mutations in the DNA of patients with pancreatic adenocarcinoma. CONCLUSION: Although hereditary pancreatitis markedly increases the risk for pancreatic cancer, it is rare and probably of little significance with respect to the pathogenesis of the majority of pancreatic adenocarcinomas.

Adenocarcinoma↗

PubMed2000

Cultures with cryopreserved hepatocytes: applicability for studies of enzyme induction.

The use of hepatocyte cultures is well established for the study of drug-drug interactions. However, the major hindrance for the use of human hepatocyte cultures is that human hepatocytes are only occasionally available. This problem could be overcome by cryopreservation. Although cryopreserved hepatocytes have been recommended for short term applications in suspension, studies on induction of enzyme activity, requiring a more prolonged maintenance of cryopreserved hepatocytes in culture, represent a new field of research. In the present study, we established a technique that allows preparation of rat hepatocyte co-cultures, using cryopreserved hepatocytes. After incubation with phenobarbital (0.75 mM; 72 h) induction factors for the isoenzyme-dependent regio and stereoselective testosterone hydroxylations were 1.6, 2.2, 1.0, 2.1, 5.6, 2.4, 3.6, 4.5 and 0.9 for 2alpha-, 2beta-, 6alpha-, 6beta-, 7alpha-, 15beta-, 16alpha- and 16beta-hydroxytestosterone and 4-androsten-3,17 dione. Regarding induction factors of less than 2-fold, as questionable these induction factors were similar to those of cultures with freshly isolated hepatocytes and the induction pattern of the individual hydroxylation products was similar to the in vivo situation. In addition 3-methylcholanthrene (5 microM; 72 h) induced exclusively the formation of 7alpha-hydroxytestosterone (6.6-fold) in cultures with cryopreserved hepatocytes. This specificity also correlates to that obtained in rats. Although these induction factors were clearly satisfactory in cryopreserved cultures, the absolute activities of the main testosterone hydroxylation products were reduced when compared to fresh cultures. For instance, 6beta-hydroxytestosterone, the main metabolite in solvent controls was reduced to 79%, 7alpha-hydroxytestosterone, the main metabolite after induction with 3-MC, was reduced to 66% and 16beta-hydroxytestosterone, the main metabolite after induction with PB, was reduced to 52%. Similarly, EROD activity after induction with 3-methylcholanthrene in cryopreserved cultures was reduced to 62%, compared with that in fresh cultures. Although further optimization and validation is required, the data show that cytochrome P450 activities can clearly be induced in co-cultures of cryopreserved hepatocytes, in a fashion which for the investigated inducers, is similar to that in cultures from freshly isolated hepatocytes and similar to the in vivo situation.

Animals↗

PubMed2000

[Primary varicose veins--changes in the venous wall and elastic behavior].

The aetiology of varicosis is still unclear. Investigation of changes in normal veins which result in the formation of varicosis led to examination of elastic properties and histomorphological alterations in the region of the extracellular matrix in the vessel wall of the long saphenous vein in normal and varicose veins. The rigidity of varicose veins was higher than that of normal veins; there was no difference between the varicose vein above a competent valve and the "normal" vein below this competent valve. The matrix proteins demonstrated an increase in total fibres, whereas the elastic fibres were reduced and fragmented, explained the rigidity of varices. These results suggest that the role of the venous valves in the development of varicose veins is secondary to changes of the vein wall.

Animals↗

PubMed2000

Changes in the extracellular matrix of the vein wall--the cause of primary varicosis?

BACKGROUND: Conflicting theories on the development of primary varicosis have led to the molecular biological investigation of the vein wall or, more accurately, of the extracellular matrix. It was the aim of this study to quantify matrix expression and to compare pathological changes in the vein wall with valve-orientated staging of varicosis, in order to determine indicators of the primary cause of varicosis. MATERIALS AND METHODS: Three hundred seventy-two tissue specimens of greater saphenous veins were obtained from 17 patients with varicosities and categorised according to Hach stage and procurement site. The specimens were compared with 36 specimens collected from six patients without varicosities, incubated with fluorescence-stained antibodies for collagen 4, laminin, fibronectin and tenascin prior to being assessed with confocal laser scan microscopy. In addition, 22 vein specimens (16 varicose, 6 normal veins) serving as negative controls were investigated. RESULTS: Image analysis and statistical evaluation showed that compared with normal veins, varicose veins are associated with a significant increase in matrix protein expression for collagen 4, laminin and tenascin. A trend towards an increase in matrix expression was further observed for fibronectin. There was, however, no difference between varicose veins and clinically healthy vein segments inferior to a varicose segment. CONCLUSION: If the findings of the present investigation can be confirmed by other studies, alterations in the vein wall may be regarded as the primary cause of varicosis and valvular insufficiency as the result of these changes.

Extracellular Matrix↗

PubMed2000

Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction.

The use of primary hepatocytes is now well established for both studies of drug metabolism and enzyme induction. Cryopreservation of primary hepatocytes decreases the need for fresh liver tissue. This is especially important for research with human hepatocytes because availability of human liver tissue is limited. In this review, we summarize our research on optimization and validation of cryopreservation techniques. The critical elements for successful cryopreservation of hepatocytes are (1) the freezing protocol, (2) the concentration of the cryoprotectant [10% dimethyl-sulfoxide (DMSO)], (3) slow addition and removal of DMSO, (4) carbogen equilibration during isolation of hepatocytes and before cryopreservation, and (5) removal of unvital hepatocytes by Percoll centrifugation after thawing. Hepatocytes of human, monkey, dog, rat, and mouse isolated and cryopreserved by our standard procedure have a viability > or = 80%. Metabolic capacity of cryopreserved hepatocytes determined by testosterone hydroxylation, 7-ethoxyresorufin-O-de-ethylase (EROD), 7-ethoxycoumarin-O-deethylase (ECOD), glutathione S-transferase, UDP-glucuronosyl transferase, sulfotransferase, and epoxide hydrolase activities is > or = 60% of freshly isolated cells. Cryopreserved hepatocytes in suspension were successfully applied in short-term metabolism studies and as a metabolizing system in mutagenicity investigations. For instance, the complex pattern of benzo[a]pyrene metabolites including phase II metabolites formed by freshly isolated and cryopreserved hepatocytes was almost identical. For the study of enzyme induction, a longer time period and therefore cryopreserved hepatocyte cultures are required. We present a technique with cryopreserved hepatocytes that allows the induction of testosterone metabolism with similar induction factors as for fresh cultures. However, enzyme activities of induced hepatocytes and solvent controls were smaller in the cryopreserved cells. In conclusion, cryopreserved hepatocytes held in suspension can be recommended for short-term metabolism or toxicity studies. Systems with cryopreserved hepatocyte cultures that could be applied for studies of enzyme induction are already in a state allowing practical application, but may be further optimized.

Animals↗

PubMed1999

Alterations of the extracellular matrix of venous walls in varicous veins.

BACKGROUND: Investigation of changes in normal veins which result in the formation of varicosis led to examination of the histological organisation of the vessel wall and to histomorphological alterations in the region of the extracellular matrix. PATIENTS AND METHODS: The expression pattern of the matrix proteins collagen IV, fibronectin, laminin, tenascin, and undulin as well as the structure and orientation of elastic fibres were determined by means of immunohistochemical staining. RESULTS: All varices exhibited an increased expression pattern in comparison to healthy veins. The venous vessel wall was often non-homogeneously enlarged. The intima was always more involved than the media and showed enhanced accumulation, whereas, the adventitia was not influenced by the pathological process. Collagen IV exhibited an early accumulation, especially in the subendothelial region. The other matrix proteins demonstrated an increase in fibre propagation parallel to the enlargement of the vessel wall. Essentially, an augmented de novo synthesis of fibres with an irregular arrangement and the formation of local plaques was found. Elastic fibres were enhanced by slight involvement of the vessel wall and were reduced and fragmented during increased involvement of the venous wall which explained the rigidity of varices in contrast to normal veins.

Elastic Tissue↗

PubMed1999

Carcinoma of the hypopharynx and the cervical oesophagus: a surgical challenge.

OBJECTIVE: To report our results after reconstruction of the upper digestive tract for locally advanced carcinoma of the hypopharynx and cervical oesophagus. DESIGN: Open study. SETTING: Teaching University hospital, Germany. SUBJECTS: Of the 517 patients who presented with carcinoma of the oesophagus between September 1985 and March 1997, 16 had a locally advanced tumour of the hypopharynx and 25 of the cervical oesophagus. INTERVENTIONS: Free jejunal grafts were used after circular resection in all patients with carcinoma of the hypopharynx, and for the 3 with oesophageal carcinoma in whom we obtained adequate resection margins. In the remainder stomach was used in 21 and colon in 1. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: After jejunal grafting 1 patient died within 30 days and 2 died in hospital. After gastric or colonic reconstruction 2 patients died within 30 days and 4 in hospital. There was 1 anastomotic leak, 1 transplant became necrotic and had to be replaced, in 2 patients the recurrent nerve was damaged, 1 patient developed a wound infection and 1 a cardiac infarction. After gastric or colonic replacement 7 patients had paralysed recurrent laryngeal nerves, there was 6 anastomotic leaks, 1 chylous leak, 1 haemorrhage, and in 1 the transplant necrosed. CONCLUSION: Despite the fact that we compared tumours in different sites, these results suggest that the jejunal graft is safer for upper oesophageal and hypopharyngeal reconstruction.

Adenocarcinoma↗

PubMed1999

Low-dose budesonide treatment for prevention of postoperative recurrence of Crohn's disease: a multicentre randomized placebo-controlled trial. German Budesonide Study Group.

OBJECTIVE: Endoscopic recurrence of Crohn's disease frequently occurs within weeks after 'curative' operation. Treatment with 3 x 1 mg oral pH-modified release budesonide was tried to prevent postoperative recurrence. DESIGN: A multicentre randomized double-blind placebo-controlled trial of 1 year duration was performed. SETTING: Departments of surgery, endoscopy and pathology of three university hospitals participated in the trial. PATIENTS: Patients with Crohn's disease who underwent ileal and/or colonic resection and whose anastomosis was accessible to colonoscopy were admitted to the study. Of the 88 randomized patients, 83 patients were included in the efficacy analysis (budesonide n = 43, placebo n = 40). Treatment was started within 2 weeks after surgery. INTERVENTIONS: Colonoscopy was performed 3 and 12 months postoperatively. The anastomosis and the adjacent bowel were evaluated by endoscopy and histology. For follow-up of the clinical course of the disease the Crohn's disease activity index (CDAI) was used. MAIN OUTCOME MEASURES: The primary outcome variable was recurrence of Crohn's disease based on endoscopic findings. Secondary efficacy variables were histology scores, CDAI, time-to-failure and global judgement of well-being of the patient. RESULTS: The recurrence rate after 1 year (endoscopic and/or clinical) was 57% (20/35) in the budesonide group and 70% (19/27) in the placebo group (n.s.). Mean time-to-failure was 196 days under budesonide and 154 days under placebo (n.s.). Median CDAI (relapse 19% vs. 28%) and global patients' judgement at the end of treatment (bad 5% vs. 15%) was slightly in favour of budesonide. One patient in each group discontinued the trial because of adverse events. Potentially steroid-related side effects were reported more frequently in the placebo than in the budesonide group (32% vs. 17%) (n.s.). SUMMARY AND CONCLUSION: Although the effect of budesonide was altogether positive in almost all variables studied in this trial (e.g. endoscopic and histopathological score, time-to-failure, CDAI, patients' global judgement and rate of side effects), this increase in efficacy was small and the power for detecting differences versus placebo was too low to be statistically significant. According to these results, low-dose oral budesonide cannot be recommended to be used for the prevention of postoperative relapse in Crohn's disease.

Administration, Oral↗

PubMed1999

Prognostic significance of tumor ploidy and histomorphological parameters in adenocarcinoma of Barrett's esophagus.

BACKGROUND: Despite recent advances in surgical and multidisciplinary treatment, the prognosis for patients with adenocarcinoma of Barrett's esophagus remains poor. The low prognostic accuracy of even surgical pathologic TNM staging suggests that additional parameters are necessary in determining the prognosis. METHOD: In a retrospective analysis of 50 patients who underwent transhiatal or transthoracic esophageal resection due to adenocarcinoma of Barrett's esophagus, a quantitative DNA analysis using image cytometry was performed in addition to the TNM classification and usual morphological criteria. At the time of DNA analysis the histomorphological parameters and survival time were not known. RESULTS: The main prognostic parameter was the curativity (R classification) of the operation. Considering only patients after R0 resection, a multivariate analysis identified the DNA ploidy, the depth of tumor infiltration and distant metastases of prognostically independent factors. Furthermore, within pT2 and pT3 tumors, which account for 80% of all the tumors, DNA ploidy allows an additional prognostic differentiation which is not possible with pT stage alone. CONCLUSION: Patients with a diploid or tetraploid tumor without distant metastasis and a tumor stage pT1-pT3 should have curative (R0) resection. In case of an aneuploid DNA content or a pT4 tumor resection alone shows no advantage as compared to palliative nonoperative procedures.

Adenocarcinoma↗

PubMed1999

[Is pancreaticoduodenectomy with portal vein resection indicated in patients with ductal pancreatic carcinoma?].

Infiltration of the portal vein is almost always regarded as a contraindication for pancreaticoduodenectomy in patients with pancreatic cancer. However, progress in many fields has changed the postoperative situation and mortality of pancreaticoduodenectomy is now below 5%. The aim of the present study was therefore to actually evaluate morbidity, mortality and prognosis of extended pancreaticoduodenectomy combined with protal vein resection for adenocarcinoma of the pancreatic head. Between September 1985 and May 1997 315 patients with a ductal pancreatic carcinoma were treated in our hospital. Resection was possible in 96 cases (partial pancreaticoduodenectomy n = 82, total pancreaticoduodenectomy n = 5, left pancreatic resection n = 9). In 10 cases the portal vein or the mesenteric vein had to be resected. Postoperative complications were seen in 25% of all cases after pancreaticoduodenectomy without portal vein resection and in 20% following extended pancreaticoduodenectomy. The mortality was 5% resp. 0% in both groups. The median survival time of patients after pancreaticoduodenectomy without portal vein resection was 11.9 months (R0 resection: 13.6 months; R1/2 resection 8 months) in contrast to 13.4 months in cases with portal vein resection. In conclusion, these results demonstrate that in special cases of adenocarcinoma of the pancreatic head extended pancreaticoduodenectomy with portal vein resection may be indicated. These patients show a better prognosis than those after palliative procedures. Morbidity and mortality of pancreaticoduodenectomy with portal vein resection is not higher as compared to pancreaticoduodenectomy alone.

Adult↗

PubMed1999

[Optimizing palliative therapy in pancreatic carcinoma].

Only an interdisciplinary approach between surgeon, medical oncologist and radiologist may allow the optimisation of palliative treatment for pancreatic carcinoma. If imaging diagnostics do not allow to decide about the resectability of a tumour, an explorative laparotomy should be performed, unless this is precluded by comorbidity. Due to similar morbidity and mortality, but better long-term results, a choloedocho-jejunostomy should be performed for intra-operatively unresectable tumors in favour of a cholecysto-jejunostomy. In selected patients a gastro-enterostomy may be indicated. However, this is not justified prophylactically. If imaging diagnostics show definite signs of unresectability in the absence of a gastric outlet obstruction, the treatment depends on the general condition of the patient: Insertion of a pigtail-catheter is sufficient for patients in poor general condition and a short life expectancy; metal wallstents should be preferred for patients in good general condition and a life expectancy in excess of six months, due to better results regarding quality of life. Chemoablation of the celiac plexus is an useful method to control the sever pain, which is common in these patients; radiotherapy or analgesic therapy may be used alternatively.

Anastomosis, Roux-en-Y↗

PubMed1999

[Amputation due to chronic peripheral vascular disease. Risks and prognosis].

A series of 181 amputations in 156 patients treated between 1985 and 1996 because of chronic peripheral vascular disease was reviewed. 107 major amputations (above- and below-knee) and 74 minor amputations (foot and forefoot) were performed. 81% of the patient population had previous vascular operations. Complications, revisions and mortality of all patients were retrospectively analyzed. The operative mortality rate of major amputations was 20% and the operative mortality rate of minor amputations was 9%. By a vessel-reconstruction before amputation the complication- (wound healing) and revision-rate could be reduced. By examination of the family-doctors, the survival times of the patients and the rehabilitation status of 69 living patients were recorded. Minor amputations, below-knee amputations and knee-disarticulations had the best results of rehabilitation.

Adult↗

PubMed1999

Drug metabolizing capacity of cryopreserved human, rat, and mouse liver parenchymal cells in suspension.

The phase I and phase II drug-metabolizing capacity of freshly isolated and cryopreserved parenchymal cells (PC) from human, rat, and mouse liver held in suspension at 37 degrees C for up to 120 min after thawing was compared. Although 7-ethoxycoumarin-O-deethylase activity was strongly reduced in freshly isolated as well as in cryopreserved PC from human, rat, and mouse liver after 120 min, 7-ethoxyresorufin-O-deethylase activity as well as the profile and formation rates of hydroxylated testosterone metabolites in general remained constant throughout the 2-h incubation period in cryopreserved PC from all three species and was similar to that measured in freshly isolated PC. The activity of glutathione S-transferase (GST) and that of UDP-glucuronosyltransferase (UDP-GT) toward 4-methylumbelliferone significantly decreased, whereas the activities of UDP-GT activity toward 4-hydroxybiphenyl and sulfotransferase in cryopreserved human PC were similar to those measured in freshly isolated PC. The activities of GST, UDP-GT toward 4-methylumbelliferone, and sulfotransferase in cryopreserved rat PC showed a significant decrease when compared with the activities in freshly isolated PC. The phase II enzyme activities in cryopreserved mouse PC proved to be far more stable, being similar to the activities of freshly isolated mouse PC at all four time points measured with the exception of GST, which showed a decay from t = 60 min onward. In conclusion, phase I drug-metabolizing enzyme activities in cryopreserved human, rat, and mouse PC are very similar to those of freshly isolated PC, whereas phase II enzyme activities are affected by cryopreservation.

Animals↗

PubMed1998

Resistance factors in colon cancer tissue and the adjacent normal colon tissue: glutathione S-transferases alpha and pi, glutathione and aldehyde dehydrogenase.

Glutathione S-transferases (GST) alpha and pi, glutathione (GSH) and aldehyde dehydrogenase (ADH) were determined in colorectal cancer tissue specimens and in the adjacent normal colon tissue. The median contents in normal and cancer tissue were 8.1 (2.3-30.3) (5-95% quantiles) and 15.1 (5.3-50.3) microg/mg protein for GST pi (P = 0.035), 0.0 (0.0-1.4) and 0.4 (0.0-3.5) microg/mg protein for GST alpha (P = 0.019), 7.3 (1.3-22.7) and 5.6 (2.3-26.0) microg/mg protein for GSH (P = 0.171) and 30.8 (13.0-42.0) and 23.2 (9.0-32.9) microg/mg protein for ADH (P = 0.0017), respectively. Thus, the mean GST alpha and pi both significantly increased in colon cancer compared to the adjacent normal tissue, which underlines their importance as possible resistance factors. A highly significant correlation was obtained between the GSH content in colon cancer and normal tissue (P = 0.0017). Thus, the constitutive GSH expression seems to be maintained during tumor development. A similar correlation was obtained for ADH (P = 0.0075), but the median ADH was lower in cancer tissue compared to the adjacent normal tissue (P = 0.0017). Contrary to GSH and ADH, GST pi did not correlate between normal and colon cancer tissue. Whereas GSH and ADH correlated in normal colon tissue (P = 0.014), no significant correlation for GSH and ADH was observed in colon cancer tissue (P = 0.109). In conclusion, significant correlations between colon cancer and normal tissue were obtained, suggesting that the expression levels of these resistance factors are maintained during carcinogenesis in most patients.

Aldehyde Dehydrogenase↗