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Biomedical subjects

K H Link

Publications and source records attributed to K H Link.

68 records · Page 4Linked to original sources

KCl carcinoma extracts as tumor antigens in the electrophoretic mobility test: clinical evaluation.

Specificity of cellular immune reactivity was tested in 182 cancer patients, 89 patients with inflammatory diseases, and 61 healthy controls. The in vitro method of electrophoretic mobility testing permitted evaluation of cellular immune reactivity. Soluble potassium chloride extracts from various human carcinomas were used as antigens. Out of 182 cancer patients 164 (90.1%) showed positive test results using extracts from tumors of the same type as the patient's tumor. Using the same tumor extracts in 61 healthy control persons, a total of 182 tests showed negative results in 156 cases (85.7%). Lymphocytic reactions to various tumor extracts varied in a typical pattern: The most pronounced migration inhibition was observed when tumor patients were tested against extracts of carcinomas of the same histogenesis. Tumor extracts deriving from different organs had a weaker or negative reaction. For each tumor a typical lymphocytic reaction pattern was noted. The method seems also to detect precancerous lesions; out of 19 patients with colorectal adenomas, 12 showed positive reactions to extracts from colorectal cancer. Inflammatory diseases of the various organs reduced the reliability of the method. Demonstrated specificity of sensitized lymphocytes could prove to be valuable aid in immunological tumor recognition.

Antigens, Neoplasm↗

[Malignant sacrococcygeal teratoma in an adult].

Malignant sacrococcygeal teratoma is rare in adults. diagnosis is difficult when the tumour is presacral located. A 42-year-old female patient underwent rectum extirpation with resection of a malignant sacrococcygeal teratoma. Histological biopsy and clinical staging did not show whether the teratomas were malignant or not. These tumours have to be resected totally, when necessary together organs of the pelvic region.

Adenocarcinoma↗

Development of two cloned epithelial cell lines from normal adult mouse and rat ventral prostates.

Two epithelial cell lines were established, one from adult C3H mouse and one from adult Fischer rat ventral prostate. These cell lines were obtained from explant cultures, using Ham's F12 medium supplemented with HEPES, insulin, testosterone, hydrocortisone, epidermal growth factor, and 7.5% fetal bovine serum. A low concentration of trypsin and EDTA in Ca++- and Mg++-free phosphate buffer was used for passaging the cells. The rat cell line was established following implantation of prostate tissue in nude mice. These cell lines stained positively for acid phosphatase and were dependent upon epidermal growth factor for growth. Morphological studies, including electron microscopy, revealed a highly characteristic epithelial morphology of both cell lines. These cell lines have hypotetraploid chromosome number and are capable of metabolizing benzo(a)pyrene. We propose the application of these cells as models for the study of prostate carcinogenesis.

Acid Phosphatase↗

In vitro concentration response studies and in vitro phase II tests as the experimental basis for regional chemotherapeutic protocols.

The theoretical pharmacologic benefit of regional vs. systemic chemotherapy is defined and the concentration response behavior of cytostatic drugs and their optimal exposure times are described with human cancer cell lines (HT29, NMG64/84) and fresh human tumor cell suspensions in the human tumor colony assay (HTCA). The theoretical pharmacological advantages are 5.8 to 6 for adriamycin (ADM), 8 for cisplatinum (CDDP), 6.3 for epidoxorubicin (EPI), 22 to 58 for 5-fluorouracil (5FU), 4.6 for mitomycin C (MMC), and 6.3 for mitoxantrone (NOV). The drugs differed in their cytotoxic potency in vitro and thus also potential efficacy for regional chemotherapy; however, all but 5-fluorodeoxyuridine (5FUDR) exerted cytotoxicity dependent on exposure time and concentration. On average, elevation of the test concentrations by 1 lg doubled responses in fresh human tumor cell suspensions. From these results and clinical considerations, optimal times were defined for the regional chemotherapy strategies of hepatic artery infusion, intraperitoneal instillation, and chemoembolisation as performed at our institution.

Antineoplastic Agents↗

Flushable stent-system for internal drainage in occlusive jaundice.

The effectiveness of biliary stents may be reduced as a result of obstruction by tumor material, bile salts or detritus. To circumvent this problem we developed a prosthesis system, which allows flushing and repetitive radiological control via a subcutaneous port. Prostheses were implanted in 26 patients presenting with inoperable occlusive lesions of the bile duct. Patency was regularly monitored by checking the bilirubin and alkaline phosphatase levels and using port-cholangiography. Catheter function was easily maintained in 92% of the patients and ended upon malignancy related death. In case of dysfunction, drainage could generally be restored with intensive flushing. This new flushable stent-system was easily implantable, could be exchanged without renewed percutaneous transhepatic puncture and allowed flushing, external drainage, bile probes for bacteriological examinations and follow up cholangiography via the subcutaneous placed port.

Cholestasis↗

Toxicity and effects of adjuvant therapy in colon cancer: results of the German prospective, controlled randomized multicenter trial FOGT-1.

In this adjuvant three-arm multicenter trial, we studied whether modulating the standard 5-fluorouracil (5-FU) treatment with either folinic acid (FA) or interferon-alpha-2a (IFN-alpha) was superior to the recommended standard of adjuvant treatment in R0 resected colon cancer, 5-FU plus levamisole (LEV) for 12 months, in terms of toxicity and outcome. From July 1992 to October 1999, a total of 813 patients with resected colon cancer in stage II (T4N0M0; n = 63) or stage III (TxN1-3M0; n = 750) were randomized into three treatment groups and stratified according to N stage and participating centers (64 hospitals). The patients received a postoperative loading dose of 5-FU (450 mg/m2 on days 1 to 5 [arms A and C]) or 5-FU (450 mg/m2) plus FA (Rescuvolin, Medac, Hamburg, Germany, 200 mg/m2 on days 1 to 5 [arm B]). After completion of the first chemotherapy cycle, LEV was administered orally at a dosage of 150 mg per day on days 1 to 3, once every 2 weeks. After a 4-week chemotherapy-free interval, the treatment was continued weekly for 52 weeks. Treatment in one arm A ("standard") (n = 279) consisted of 5-FU intravenously (450 mg/m2 on day 1, once a week) plus LEV. 5-FU plus LEV was modulated in arm B (n = 283) with FA (200 mg/m2 on day 1, once a week) and in arm C (n = 251) with IFN-alpha at 6 million units three times a week repeated weekly. Treatment dosages were adjusted if toxic events above WHO grade 2 occurred. Patients were closely followed to determine recurrence and survival; the latter was calculated according to Kaplan-Meier analysis. Toxic events above WHO grade 2, mainly leukopenia, diarrhea, and nausea, occurred in 113 (14%) of 649 patients who had completed treatment in arms A (8.4%), B (13.5%), and C (31.7%). Discontinuance rates were as follows: 28% for all patients, 29% in arm A, 21% in arm B, and 34% in arm C. Overall relapse rates were 27% for all patients, 30% in arm A, 24% in arm B, and 28% in arm C. Relapses were local (8%), distant (78%), or combined (12%). Four-year overall survival rates in arms A, B, and C were 66.1%, 77.5%, and 66.2%, respectively. The 4-year survival rate in arm B was significantly higher compared to arm A (P <0.02, log-rank test) with arm A being equal to arm C. Adjuvant therapy with 5-FU plus FA plus LEV for 12 months is superior to the recommended standard (5-FU + LEV for 12 months). IFN-alpha modulation of 5-FU (plus LEV) adds to the toxicity with no therapeutic benefit.

Adjuvants, Immunologic↗

Oxaliplatin exerts potent in vitro cytotoxicity in colorectal and pancreatic cancer cell lines and liver metastases.

BACKGROUND: Oxaliplatin displays potent activity in advanced colorectal cancer. The aim of this study was to estimate the potential efficacy of oxaliplatin for hepatic arterial infusion (HAI) chemotherapy. MATERIALS AND METHODS: The anti-proliferative effects of oxaliplatin in human HT29 and NMG64/84 colon and COLO-357 MIA PaCa-2 and PMH2/89 pancreatic cancer cell lines and in fresh liver metastases from patients with colorectal and pancreatic cancer were investigated using the human tumor colony forming assay. RESULTS: Oxaliplatin significantly inhibited the colony formation in all cell lines in a concentration- and time-dependent manner. All liver tumors displayed a significant concentration-dependent inhibition of colony formation after exposure to oxaliplatin for 2 hours. The IC50 of oxaliplatin of 9 of the 10 tumors was < 10 micrograms/ml. CONCLUSION: Oxaliplatin is suitable for HAI therapy phase II studies. Due to the low IC50 values of most tumors we suggest that patients with colorectal or pancreatic liver metastases may benefit from HAI with oxaliplatin.

Aged↗

Regional celiac artery infusion in the adjuvant treatment of pancreatic cancer.

UNLABELLED: We performed adjuvant celiac artery infusion in pancreatic cancer, to find out whether this treatment prolongs survival and changes the biology of the disease after resection, especially by reducing liver metastasis. PATIENTS AND METHODS: Thirty-one patients received cyclic celiac artery infusions (CAI) after resection of their pancreatic cancer (27 ductal, 4 cystadenocarcinoma). The treatment consisted of 6 cycles (1 cycle = 5 days treatment) intra-arterial infusion using Seldingers technique with mitoxantrone A (Novantron) 10 mg/m2 d1, 5-fluorouracil + folinic acid 600 mg/m2 + 170 mg/m2 d2-d4 and cis-platinum 60 mg/m2 d5. Four to 5-week intervals between each cycle of chemotherapy were scheduled. The patients were monitored for toxicity, development of disease progression and survival. RESULTS: The median survival time was 21 months. During an observation period of 19 months, 70% of the patients developed disease progression. In 50% of cases the progression was local, in 40% intraperitoneal while in 15% liver metastases developed. The median survival time of the CAI (celiac artery infusion)-treated patient group compared favorably to the median survival of 9.3 months in a matched historical control group, being significantly longer (p < 0.0003). CONCLUSION: Adjuvant celiac artery infusion seemed to prolong median survival and the occurrence of liver metastases appeared to be delayed or reduced.

Adenocarcinoma↗

Regional perfusion of VX 2 carcinoma with cis-DDP.

High dose effect of regionally applied cis-DDP was studied using VX 2 carcinoma as a tumor model. The tumors were transplanted on both hind limbs of New-Zealand rabbits. After strict standardization of the methods, treatment with cis-DDP systemically was compared to regional treatment with cis-DDP by isolated perfusion on extremities. These results were related to untreated controls. Therapeutic effect was determined by comparing the average tumor diameters at various time points after the end treatment. Remission could be induced for a short period by systemic treatment. After isolated perfusion, remission was continuous during the observation period. There was no therapeutic benefit by a dose increase from 20 to 40 mg cis-DDP/kg limb weight.

Animals↗

Adjuvant regional chemotherapy in advanced pancreatic cancer: results of a prospective study.

BACKGROUND/AIMS: In order to improve the dismal prognosis of patients suffering from advanced pancreatic cancer we treated 20 patients with adjuvant regional chemotherapy following resection of the tumor. METHODOLOGY: All tumors were classified UICC stage III (TxN1M0). Regional chemotherapy consisted of Mitoxantrone 10 mg/m2 day 1, Folinic Acid 170 mg/m2 and 5-FU 600 mg/m2 days 2-4, and cis-Platinum 60 mg/m2 day 5 for up to 6 cycles. In a total of 101 cycles toxicities WHO III occurred in 6%, WHO IV in 0%. RESULTS: The median survival times, compared to institutional historical controls (treated vs. controls) were 18.5 vs. 9.3 months (p < 0.0006). Hepatic disease progression seemed to be suppressed. CONCLUSION: In conclusion regional chemotherapy seems to be effective for adjuvant treatment in resected pancreatic cancer.

Adult↗