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Biomedical subjects

K H Link

Publications and source records attributed to K H Link.

At least 55 records · Page 3Linked to original sources
PubMed1996

CAM 17.1--a new diagnostic marker in pancreatic cancer.

CAM 17.1-Ab is a recently described monoclonal antibody that detects a mucus glycoprotein with high specificity for intestinal mucus, particularly in the colon, small intestine, biliary tract and pancreas. We investigated the expression and release of CAM 17.1 in pancreatic carcinoma cell lines and tissue specimens of normal pancreas, chronic pancreatitis and pancreatic cancer. CAM 17.1 was weakly expressed on normal ductal cells and chronic pancreatitis, whereas it was overexpressed in pancreatic cancer. Serum analysis using a new enzyme-linked antibody sandwich assay (CAM 17.1/WGA) of patients with chronic pancreatitis, pancreatic cancer or other gastrointestinal cancer and of healthy blood donors revealed a high sensitivity (67%) and excellent specificity (90%) of CAM 17.1/WGA assay in pancreatic cancer. In comparison with the tumour marker CA19-9, the sensitivity of the CAM 17.1/WGA assay was similar to the sensitivity of CA 19-9 (67% and 76%, P = 0.22), whereas the specificity of CAM 17.1/WGA assay was higher than in CA 19-9 (90% compared with 78% in chronic pancreatitis, P > 0.05).

Adult↗
PubMed1996

[Adjuvant regional chemotherapy in resected advanced pancreas carcinoma].

Systemic chemotherapy in patients who underwent resection of pancreatic carcinoma has not been significantly improved median survival times. We investigated whether regional chemotherapy administered via celiac trunc infusion increases survival rates in patients with locally advanced pancreatic carcinoma after resection of the primary. From 12/1992 to 2/1995 we treated 18 patients with regional chemotherapy consisting of mitoxantrone (d1), 5-FU + folinic acid (d2-4) and CDDP (d5) on five consecutive days. This cycle was repeated up to 6 times. Besides non-symptomatic GI-ulcerations (3/18) no severe side effects were observed. The median survival is actually 17.8 months (regression analysis). Compared to a historical control of our department survival times are significantly prolonged (17.8 vs. 9.3 months, p < 0,0003). In conclusion we state that adjuvant regional chemotherapy in patients with advanced pancreatic cancer is well tolerated and prolongs survival significantly.

Aged↗
PubMed1996

Regional chemotherapy directed by individual chemosensitivity testing in vitro: a prospective decision-aiding trial.

A prospective decision-aiding trial was performed to select drugs for regional chemotherapy of various liver tumors (n = 36) by individual drug testing. The drugs were chosen for hepatic artery infusion according to the individual chemosensitivity of tumor biopsies in the human tumor colony-forming assay (HTCA). In vitro HTCA sensitivity correlated with complete response (CR) + partial response (PR) + no change (NC) 93% of the time and with CR + PR 55% of the time. The test sensitivity was 90%, and the specificity was 67% for CR + PR + NC versus progressive disease (PD), whereas the sensitivity and specificity were 89% and 28%, respectively, for CR + PR versus NC + PD. The overall predictive accuracy of the test was 86% for CR + PR + NC versus PD and 58% for CR + PR versus NC + PD. Overall, 83% of this heterogenous patient group with various tumors achieved CR + PR + NC and a 50% clinical response (CR + PR). In vitro-sensitive patients showed a significantly lower intrahepatic progression rate (7% PD) than in vitro-resistant patients (57%; P < 0.05). These results indicate that the HTCA could identify active drugs for individualized hepatic artery infusion, and patients may profit from the use of in vitro-sensitive drugs.

Adult↗
PubMed1995

Differential expression of CD44 splice variants in human pancreatic adenocarcinoma and in normal pancreas.

Immunohistochemical screening of pancreatic adenocarcinomas from 24 different patients and 9 pancreatic carcinoma cell lines revealed variant CD44 expression in all specimens tested. In contrast to normal pancreatic tissue, carcinomas were strongly positive for epitopes encoded by variant exons v5, whereas v6 was expressed on carcinoma cells as well as normal ductal pancreatic cells. Analysis of RNA expression revealed clear differences between normal pancreatic tissue and tumor specimens. In normal pancreas, v6 and v3 solely and one major chain consisting of v6-v10 were expressed, whereas in pancreatic carcinoma, multiple splice variants were detected. In about 80% of all carcinoma cases and all cell lines tested, the exon v5 appeared in the chain containing at least v4-v10. These data thus far suggest that not the presence alone but the chain composition of the CD44 variant chains could be important for their altered function because one of the major differences between normal and cancer tissue is the linkage of CD44v5 to the CD44v6-containing chain.

Adenocarcinoma↗
PubMed1995

[Regional chemotherapy in advanced pancreatic carcinoma].

BACKGROUND: Even after resection median survival times in advanced pancreatic carcinoma are seldom more than one year. The aim of our study was to evaluate the effectivity of regional chemotherapy in patients suffering from unresectable pancreatic cancer. PATIENTS AND METHODS: From 2/92 until 11/94 32 patients with unresectable pancreatic cancer (17 patients stage III, 15 patients stage IV) were treated by celiac trunc infusion. One cycle consisted of mitoxantrone (d 1), 5-FU, folinic acid (d 2 to 4) and cisplatinum (d 5). RESULTS: Besides a few severe complications, therapy was well tolerated in 101 cycles. In unresected patients with stage III tumors the median survival is 12 months compared to 4.8 months in patients with biliodigestive bypasses (p < 0.006) and 4 months in regionally infused patients stage IV compared to 2.7 months in untreated patients (n.s.). CONCLUSION: Regional chemotherapy in advanced pancreatic carcinoma is well tolerated and increases median survival in patients with stage III tumors.

Adenocarcinoma↗
PubMed1993

Is follow-up of colorectal cancer patients worthwhile?

Between 1978 and 1989, 1,045 of 1,399 patients (580 male and 474 female) underwent curative surgery for colorectal carcinoma. Of these patients, 350 (33 percent) had recurrences, another 16 (1.5 percent) developed a metachronous colorectal cancer, and 23 (2 percent) had cancers of other organs. An isolated locoregional recurrence was found in 75/350 (21 percent). The remaining 275/350 patients (79 percent) showed systemic dissemination of the carcinoma. Reoperations with curative intent were performed on 56/350 patients (16 percent). Only 21 of the 56 resected patients (38 percent), i.e., 21/350 (6 percent), were without recurrence at the end of the follow-up period on December 31, 1990. Despite a curative reoperation, 62 percent of the patients again developed recurrent growths. There is an imbalance between the efforts invested in tumor follow-up and the benefits gained. Further follow-up programs should be investigated in a controlled, prospective fashion.

Adolescent↗
PubMed1992

[What is confirmed in chemo- and immunotherapy of solid tumors. Standard protocols, studies and new developments].

Reviewing the treatment perspectives with chemo- and immunotherapy in carcinomas and sarcomas to be treated by general or orthopedic surgeons, the following indications are regarded as recommendable: Adjuvant chemotherapy in breast cancer, neoadjuvant chemotherapy with radiation in anal carcinoma and neoadjuvant/adjuvant chemotherapy of high-grade malignant osteosarcoma. Isolation perfusion currently is the treatment of choice in melanoma metastasis limited to an extremity. With several indications, recent developments have produced promising results that should be urgently confirmed in appropriate studies. Therefore the following studies have a high priority: Neoadjuvant chemotherapy in esophageal carcinoma and in locally advanced breast and stomach cancer, adjuvant chemoimmunotherapy in colon carcinoma UICC III and chemoradiation in rectal carcinoma UICC II and III, systemic chemotherapy of metastasized stomach-, colorectal-, breast cancer and sarcomas. Isolated non-resectable liver metastases of colorectal origin and hepatocellular carcinoma should be included in studies evaluating the treatment advantage of regional chemotherapy. Those malignant "surgical" tumors not listed above should receive chemotherapy within experimental studies, after consideration of individual risk factors, or no chemotherapy. Immunotherapy with its various modalities is still in the experimental stage.

Antineoplastic Agents↗
PubMed1989

[Systemically administered regional tumor therapy. Regional hemi-body chemotherapy of metastatic malignant melanoma--an experimental therapy concept].

Since systemic application of a high-dose chemotherapy is limited by the extent of intolerable toxicity and overall response rates so far are rather poor, the systemic mode of chemotherapy for metastatic melanoma appears to be of only limited benefit. On the other hand, results from isolated limb perfusion for satellitosis and in-transit metastasis suggest distinct dose-response correlations with tumoricidal properties of appropriate antineoplastic agents. This experience prompted the idea to pilot the anti-tumor action of a high-dose regimen confined to one hemibody compartment for targeted tumor therapy. After having standardized the surgical procedure this goal appeared to be achievable by expanding the perfused area and by simultaneously detoxifying toxic drug levels within the non-perfused compartment by venous filtration. Two initial causal experiences revealed impressive tumor regressions and are therefore reported on preceding subsequent evaluation within a controlled clinical trial being designed at different solid tumors.

Adult↗
PubMed1989

[In vitro interaction of mezlocillin with fluorouracil and mitomycin].

The interaction of mezlocillin (Baypen) with either fluorouracil (5-fluorouracil, 5-FU) or mitomycin was tested in vitro by incubating colorectal carcinoma cell line HT 29 with varying concentrations of mezlocillin, 5-FU, mitomycin and the combinations of mezlocillin + 5-FU and mezlocillin + mitomycin. Inhibition of colony growth in soft agar of treated compared with untreated cells was used as an in vitro response parameter. Concentration ranges were representative for regional chemotherapy with mitomycin or 5-FU and perioperative antibiotic therapy with mezlocillin. Mezlocillin, 5-FU and mitomycin showed dose-dependent inhibition of colony growth. Mezlocillin produced a maximal toxicity of 16% at 1000 micrograms/ml. Toxicity of 5-FU was reduced by addition of mezlocillin. The increase of colony growth after coincubation of mezlocillin with 5-FU (compared to cells treated with 5-FU alone) at a mezlocillin concentration of 10 micrograms/ml was 47% to 116%, at 100 micrograms/ml 44% to 132%, depending on the 5-FU test concentrations. The 5-FU toxicity in some instances was nearly abolished. There was no interaction between mezlocillin and mitomycin. The interference of mezlocillin with 5-FU-toxicity should be respected in case of combined perioperative antitumor and antibiotic therapy with 5-FU mezlocillin. Similar interactions with related antibiotics cannot be excluded.

Cell Survival↗
PubMed1988

Concentration and time dependence of the toxicity of fluorinated pyrimidines to HT 29 colorectal carcinoma cells.

To determine the optimal concentration time factors for the fluoropyrimidines 5-fluorouracil (FU), 5-fluorouridine (FUR), and 5-fluoro-2'-deoxyuridine (FUdR) in regional chemotherapy, we tested these drugs against the colorectal carcinoma cell line HT 29 at various dosages and exposure times. The measure of cytotoxicity used was the degree of inhibition of colony formation in soft agar after drug treatment compared with untreated control cells. Colonies were visible after 6 days of growth in soft agar, so the initial evaluation of toxicity was done at this time. Additional colonies were found 10 and 16 days after the first evaluation, so the dishes containing the treated cells were also evaluated for this delayed growth phenomenon ("regrowth"), which we considered to be due to a cell growth inhibition effect of the drugs rather than a cytocidal effect. Exposure times of the cells to the drugs ranged from 5 min to 24 h and the doses, between 0.01 and 1000 micrograms/ml. The toxicity of FUdR was concentration-dependent, but its time dependence ceased after a relatively short exposure time. There was a cell population that was not susceptible to FUdR regardless of dose and exposure time; consequently, FUdR treatment was always accompanied by substantial regrowth of colonies. With FU and FUR, conditions could be achieved that resulted in complete cell death (no regrowth), but high concentrations and long exposure times were required with FU. With FUR, on the other hand, both cytostasis and cytotoxicity could be achieved with substantially lower doses and shorter exposure times than with FU. These results indicate that FUR has the potential to be an effective drug in chemotherapy protocols not involving systemic administration.

Cell Line↗
PubMed1986

Prospective correlative chemosensitivity testing in high-dose intraarterial chemotherapy for liver metastases.

Clinical response of liver metastases treated by high-dose intraarterial chemotherapy (HDIAC) delivered via the hepatic artery was predicted by a modification of the human tumor colony-forming assay (HTCFA) originally described by Hamburger and Salmon [Science (Wash. DC), 197:461-463, 1977. In a first set of experiments, the immediate clinical response to HDIAC was determined in 12 patients with colorectal liver metastases. Biopsies were taken immediately before and after HDIAC, and cells were plated in the HTCFA. Three patients received intraoperative 4-epidoxorubicin and another 9 received mitomycin C by 15-min intraarterial infusions. Sensitivity in the HTCFA was defined as 50% inhibition of colony formation in tumors exposed to the chemotherapeutic agent, compared to the untreated controls. Clinical response was accurately predicted by the HTCFA in 11 of 12 cases. Eight patients had a regression of disease following HDIAC treatment with mitomycin C, as evidenced by either greater than 50% reduction in carcinoembryonic antigen serum level (7 patients) or regression of tumor by computed tomography scan (1 patient). Three patients had no evidence of clinical response to epidoxorubicin, and their tumors were resistant to epidoxorubicin in the HTCFA. One tumor was sensitive to mitomycin C in the HTCFA, but serum carcinoembryonic antigen in the patient continued to increase following HDIAC. The HTCFA was also performed on untreated biopsies following incubation in vitro with the drug used for HDIAC. Results correlated with clinical response in all 12 cases. In a second set of experiments, the HTCFA was used to predict the long-term clinical response to HDIAC of 30 patients with liver metastases. One patient had breast cancer metastases, one patient had carcinoid liver metastases, 4 had liver metastases of malignant melanoma, and 24 patients had colorectal liver metastases. All 21 of the patients whose tumors were sensitive in vitro had clinical response, while 6 of 9 patients predicted by the HTCFA to be resistant had no clinical response. Our results demonstrate a high correlation between the HTCFA and clinical response.

Antineoplastic Agents↗
PubMed1985

[Reduction of postoperative edema following isolated hyperthermic perfusion of the extremities with prophylactic administration of aprotinin. Preliminary results].

Experience from more than 380 operations resulted in the standardisation of isolated hyperthermic perfusion with cytostatic drugs for the treatment of malignancies of the extremities. A side-effect of this procedure is postoperative oedema in varying degrees of severity. The influence of prophylactic intraoperative administration of aprotinin (Trasylol) was investigated under experimental and clinical conditions. In these preliminary studies aprotinin distinctly reduced maximum extent and duration of the postoperative oedema. An investigation concerning interaction of aprotinin with the cytotoxic activity of the drugs used in perfusion showed only minor inhibition which does not limit clinical usefulness.

Animals↗
PubMed1984

[Isolated liver perfusion in advanced metastases of colorectal cancers].

A special cannulation system was developed in order to completely isolate the liver in an extracorporeal circuit. Isolated hyperthermic liver perfusion at 40 degrees C with an average dosage of 1000 mg 5-FU was performed in 32 patients with liver metastases (29 colorectal carcinomas, 2 carcinoids, 1 primary hepatoma). 12 patients who had an overall 45% tumor invasion of the entire liver-volume as measured in CT-scan were treated exclusively by isolated liver perfusion. In that group median survival was 8 months and death occurred in the presence of extrahepatic metastases. Better results are achieved with isolated liver perfusion followed by intraarterial short-time infusions (Mitomycin C/5-FU) via an Implantofix catheter. Median actual survival in this group is 12 months, the longest follow-up period is 23 months.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed1984

[Isolated hyperthermic extremity perfusion with vindesine, dacarbazine and cisplatin in the treatment of malignant melanomas].

A three drug combination consisting of dacarbazine, vindesine and CDDP (DVP) was used for isolated extremity perfusion in 26 patients with stage I, II and III melanomas of the limbs. Dosages of 100 mg/l dacarbazine, 0.4 mg/l vindesine and 20 mg Cis-Platinum/l extremity volume have been tolerated without major side effects. All perfusions of bulky tumors or metastases resulted in more than 50% tumor-size reduction (8 patients stage III A, 6 patients stage III AB). In five stage III patients relapse occurred 2, 3, 5, 6 months after isolated DVP perfusion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Induction of ouabain-resistant mutants by chemical carcinogens in rat prostate epithelial cells.

We determined optimal conditions to quantitatively select ouabain-resistant (Ouar) mutants induced by chemical carcinogens in a rat prostate epithelial cell line (RPYK). These conditions included selection of Ouar mutants in 3 mM ouabain, an expression time of two days following a two-day treatment with carcinogens, and a reseeding density of 2 X 10(5) mutagenized cells per 100 mm dish to select mutants in ouabain. Ouar mutants induced by N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG) remained stably Ouar when passaged in nonselective medium. Hemicyst formation, a characteristic of epithelial cells, was reversibly inhibited by ouabain in wild-type cells and was resistant to ouabain in Ouar cells. The direct-acting carcinogens MNNG and methylazoxymethanol-acetate (MAMA) and the environmentally widespread procarcinogens aflatoxin B1 and benzo(a)pyrene increased the frequency of Ouar mutants in RPYK cells. The procedures developed here now make it possible to detect some environmental carcinogens likely to cause prostate cancer by virtue of their ability to mutate cultured prostate epithelial RPYK cells. The sensitivity of the RPYK cell line to aflatoxin-induced cytotoxicity and mutagenesis also makes it a useful cell system in which to study enzymes governing the conversion of aflatoxin to genotoxic metabolites.

Aflatoxin B1↗