PubMed HealthSearch

Biomedical subjects

C U Ludwig

Publications and source records attributed to C U Ludwig.

10 recordsLinked to original sources

Allelic loss on the short arm of chromosome 11 in non-small-cell lung cancer.

Forty-eight samples of primary non-small-cell lung cancer (NSCLC) and normal tissue from the same patients were analyzed for allelic deletions on chromosome 11p. Five polymorphic loci were assessed to determine the incidence of 11p sequence deletions and to define hot-spots of deletions. Information was obtained from all patients in at least one locus. Our data show that the deletions observed were not randomly scattered over the short arm of chromosome 11. Rather, 2 hot-spots of deletions were observed: one in the area of the genes for catalase and beta-FSH corresponding to band 11p13, the other close to the IGF-II locus corresponding to band 11p15. A high incidence of loss of heterozygosity (LOH) was found with the probe for catalase (21/29), a locus flanking the centromeric region of the Wilms' tumor locus. Most of the samples exhibiting LOH of one or more of the alleles analyzed remained heterozygous for at least one other chromosome 11p allele. Furthermore, duplication of the intensity of the remaining allele was rarely observed. Our results indicate that LOH on the short arm of chromosome 11 is a common event in NSCLC and that the chromosomal region containing the Wilms' tumor locus is most commonly involved.

Alleles

[Therapy of bronchus carcinoma: therapeutic possibilities and current molecular biology trials].

Clearcut progress has been achieved in the treatment of lung cancer in the last decade. While small cell lung cancer has proven a highly chemosensitive tumor, only remissions of relatively short duration are obtained. The high relapse rate is probably due to the reappearance of chemoresistant subclones. In contrast, non small cell lung cancer is often chemoresistant from the outset, a fact which limits the therapeutic possibilities in these tumors. Different forms of chemoresistance are described and potential modalities of circumventing or reversing it are discussed. In recent years, greater insight into molecular mechanisms of tumor formation has been achieved. The role of activation or overexpression of oncogenes has been demonstrated. More recently the role of tumor suppressor gene inactivation has become evident. By means of restriction fragment length polymorphism (RFLP) a combination of gene deletions in various chromosomes has been demonstrated in lung cancer. The pattern of chromosomes involved appears to vary between small cell and non small cell lung cancer. It is to be hoped that these new insights will be translated into new treatment modalities for lung cancer.

Antineoplastic Combined Chemotherapy Protocols

Improved tolerance of interferon alpha-2a by continuous subcutaneous infusion.

Fifteen patients with progressing melanomas, hypernephromas or B-cell malignancies were treated in a phase I study with Interferon (IFN) alpha-2a by continuous subcutaneous infusion. With the help of a syringe driver pump daily doses of 12-15 MU resulting in median weekly doses of 90 MU could be safely given with little side effects. Flu-like symptoms and side effects from the gastrointestinal tract were mainly of grade 1 or 2 only. The major dose limiting but reversible toxicity was leukopenia. Five patients developed local inflammatory reactions at the infusion site. The pharmacokinetic data demonstrate that by this route of administration median serum levels of 54 IU/ml (range 9.6-192.0 IU/ml) (EIA-F-assay) can be achieved. Antibody formation was observed in 4 patients. - One out of 9 patients evaluable for tumor response demonstrated a partial tumor regression and 4 patients had a stabilisation of their disease. In comparison to intermittent i.m. or s.c. schedules, this novel route of administration by continuous subcutaneous infusion results in significant serum concentrations, biological activity and little clinical side effects. This may facilitate in the future the combination of IFN alpha-2a with other biological response modifiers like interleukin-2 or tumor necrosis factor.

Adult

[Possibilities and limits of the use of interferons in the clinic].

Only the recent production of large amounts of highly purified recombinant interferons has made it possible to elucidate precisely the in vitro and in vivo effect of alpha- and gamma-interferon. Interferon-alpha has significantly widened the treatment modalities for some rare tumors such as hairy cell leukemia and chronic myelogenous leukemia. Although treatment results in solid tumors are disappointing, tumor regression greater than 50% is achieved in 15-25% of patients with hypernephroma or melanoma, cancers highly resistant to cytotoxic drugs. The solid tumors must be treated with high doses of interferon-alpha which causes severe side effects. Interferon-induced toxicity can be reduced by continuous subcutaneous infusion. Interferon-alpha is also used for the treatment of viral diseases such as chronic hepatitis-B, as well as for patients with AIDS and Kaposi sarcoma. Other virus infections such as herpes simplex and condylomata acuminata represent the few established indications for treatment with interferon-beta. Interferon-gamma has distinct immunomodulatory effects in vitro and in vivo, although the clinical significance of this potential has not yet been established. Thus far the treatment results in tumor patients have been poor. The future will show if the combination of interferons with other biological response modifiers, such as tumor necrosis factor or interleukin-2, or with cytotoxic drugs, brings further progress in cancer treatment.

Humans

[Infusion pumps and subcutaneously implantable catheter systems as an aid in the ambulatory care of tumor patients].

Totally implantable catheters have greatly improved therapy and supportive care of tumor patients. Venous catheters can reduce the problem of maintaining reliable vascular access and the risk of cytotoxic drug extravasation. In addition, epidural or intrathecal catheter systems can result in an improved pain relief and in reduced side effect incidences in many patients suffering from severe cancer pain. The intraarterial and intraperitoneal catheters facilitate loco-regional chemotherapy. If used by an experienced team, most of these systems have a relatively low complication rate. The combination of such catheters with portable pumps does further facilitate the management of ambulatory tumor patients and will improve their quality of life.

Ambulatory Care

[A total subcutaneously implantable venous catheter system. 4 years' experience in cancer patients].

A totally implantable venous access system (Port-a-Cath) was inserted in 48 cancer patients. The devices were utilized for the administration of chemotherapy, antibiotics and blood products, as well as for blood drawing. Implantation was possible on an outpatient basis. The system provided full physical activity and good quality of life for the patient. Complications related to the Port-a-Cath were one subclavian vein thrombosis, one catheter thrombosis, two catheter dislocations, one dislocation of the "port" and reduced blood aspiration in two cases. It is stressed that no catheter related infections were seen. With increasing experience of the team the complication rate was significantly reduced.

Anti-Bacterial Agents

Prevention of cytotoxic drug induced skin ulcers with dimethyl sulfoxide (DMSO) and alpha-tocopherole.

Accidental subcutaneous extravasation of several antineoplastic agents may provoke skin ulcerations for which there has been no simple and effective treatment. Since January 1983 we have treated all patients in our institution sustaining extravasation by a cytotoxic drug with a combination of DMSO and alpha-Tocopherole. During the first 48 hr after extravasation a mixture of 10% alpha-Tocopherole acetate and 90% DMSO was topically applied. The bandage was changed every 12 hr. So far eight patients with extravasation of an anthracycline or Mitomycin were treated on this protocol. No skin ulceration, functional or neurovascular impairment occurred in any of these patients. The only toxic effect observed by this treatment was a minor skin irritation. The combination of DMSO and alpha-Tocopherole seems to prevent skin ulceration induced by anthracyclines and Mitomycin.

Administration, Cutaneous

[Multiple myeloma].

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols

Unaltered immunocompetence in patients with non-disseminated breast cancer at the time of diagnosis.

Immunologic parameters were examined preoperatively in 104 patients with breast cancer, staged according to the TNM classification and in 95 age-matched healthy women. The immunologic evaluation in the peripheral blood included lymphocyte and monocyte counts, determination of E-rosette-forming T-lymphocytes (SER+) and B-lymphocytes (MER+), T-lymphocyte subsets defined with monoclonal antibodies (Leu-1, Leu-2a, Leu-3a) and with lectin fractionation (soybean agglutinin), lymphocyte transformation test with phytohemagglutinin (PHA) and concanavalin A (ConA), and colony formation of T-lymphocytes in agar (T-lymphocyte colony-forming cells, [TL-CFC]). Two age groups (Group A: 30-50 years; Group B: 51-70 years) and the different tumor stages (Stage I-IV) were analyzed. Patients and controls did not differ in the absolute numbers of lymphocytes, T- and B-cells. In patients of Group B, the absolute number of monocytes was increased slightly in Stage II and III and significantly in Stage IV (P less than 0.05). Similarly, the lymphocyte response to PHA was significantly reduced in Stage IV Group B only (P less than 0.05). ConA-induced lymphocyte proliferation and TL-CFC capacity were not different in patients and controls. In the small number of patients and age-matched controls in whom T-lymphocyte subsets were determined, the absolute numbers of T-cells with helper or suppressor phenotype as defined with Leu-3a, Leu-2a, or lectin fractionation with soybean agglutinin were similar. This study demonstrates that in patients with early breast cancer (Stage I-III), immunocompetence as defined by either functional in vitro studies or surface marker analysis is not significantly altered at the time of diagnosis. In contrast, patients with advanced disease (Stage IV) show a significant increase in the absolute number of monocytes and a depressed PHA responsiveness of mononuclear cells.

Adult