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Biomedical subjects

K Sikora

Publications and source records attributed to K Sikora.

At least 19 recordsLinked to original sources
PubMed1992

Gene therapy for cancer.

The molecular basis of cancer is now understood to involve activation of dominant oncogenes and inactivation of tumour suppressor genes, and these genetic events may represent novel targets for cancer therapy. This review focuses on the potential use and ethical implications of gene transfer to alter the behaviour of somatic cells in cancer patients. Antisense nucleic acids and ribozymes represent informational drugs that may be used to modulate the expression of selected genes and suppress malignant behaviour in cancer cells. Genetic immunomodulation by introducing genes for cytokines into cancer cells or lymphocytes can stimulate a cytotoxic immune response against the tumour. Gene transfer techniques can be applied to target prodrug activation specifically to tumour cells and also to protect normal tissues against toxic chemotherapy. Gene replacement therapy could even be used to restore the function of defective tumour suppressor genes.

Animals↗
PubMed1992

Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and noninvasive dynamic method.

A noninvasive dynamic method for the measurement of blood flow, using 15O-labeled water and positron emission tomography, has been developed and used to study 20 patients with breast carcinoma. The mean tumor flow was 29.8 +/- 17.0 (SE) ml/dl/min of tissue, while normal breast flow was 5.6 +/- 1.4 ml/dl/min of tissue. The exchanging water space of tissue known as the volume of distribution of the tracer (Vd) was also derived. This is defined as the volume of water in tissue that exchanges with a unit volume of water in arterial blood during the period of the study (7 min). The mean tumor Vd was 0.56 +/- 0.15 ml/ml while normal breast Vd was 0.14 +/- 0.05 ml/ml. The low value in normal breast is partly due to the high fat content of the tissue. The mean flow per unit of exchangeable volume was similar in tumor (52.8 +/- 22.0) and normal breast tissue (45.2 +/- 20.0). This suggests that the major discrepancy seen in measured values of flow between breast tumors and normal breast principally reflects the different composition of the two tissues. This method is rapid and suited for studying the reactivity of human tumor vasculature, so extending studies are being performed on animal tumors.

Adult↗
PubMed1992

Bladder cancer: inter-relationships between chemotherapy and radiotherapy.

There has been increasing interest in the role of chemotherapy as primary treatments for patients with urothelial cancer and because of the poor prognosis of locally advanced tumours with conventional treatment, trials have been initiated comparing radiotherapy with chemotherapy as primary therapies. In this context it is important to assess the relationship between the responses to chemotherapy and radiotherapy, and this we have examined in 64 patients treated with MVMJ (methotrexate, vinblastine, mitozantrone and carboplatin). Either a complete or a partial response was found in 29 of the 64 patients, 15 had stable disease and 13 had progression of disease. Seven patients died within the first treatment month. The survival of the responding patients ranged from 114 to 1184 days. Six of 15 patients who had had pelvic irradiation prior to chemotherapy responded to MVMJ, the maximum duration of response being more than 3 years. Twenty-two patients had radiotherapy following their chemotherapy. One of 13 patients not responding to MVMJ had a transient response to radical radiotherapy. Only 1 of 9 patients responding to chemotherapy and then relapsing responded to subsequent radical radiotherapy. Patients with metastatic disease or with recurrent disease after radiotherapy have a worthwhile chance of responding to chemotherapy and achieve durable remissions. In contrast, radiotherapy appears relatively ineffective in patients whose disease progresses or relapses after chemotherapy given as primary treatment with curative intent.

Adult↗
PubMed1991

Comparison of dexamethasone and ondansetron in the prophylaxis of emesis induced by moderately emetogenic chemotherapy.

A multicentre, randomised, double-blind, cross-over trial was done to compare the efficacy and safety of a serotonin receptor antagonist--ondansetron--and dexamethasone in the prophylaxis of acute and delayed emesis and nausea induced by moderately emetogenic non-platinum-containing chemotherapy regimens. Patients were treated as outpatients and received intravenous ondansetron 4 mg or dexamethasone 8 mg before chemotherapy and oral maintenance (ondansetron 4 mg every 6 h and dexamethasone reducing from 4 mg to 1 mg 6-hourly between days 1 and 5) for 5 days. 112 patients were treated (38 men, 73 women, 1 with no gender recorded; age range 30-73 years) and 100 were evaluable for cross-over analysis. Patients taking ondansetron or dexamethasone reported no significant difference in complete and major control of acute (83% vs 79%, p = 0.46) or delayed (82% vs 88%, p = 0.214) emesis (vomiting plus retches). Significantly more patients on dexamethasone (87%) than on ondansetron (72%) reported control of delayed nausea (days 2-5) (p = 0.003). Both drugs were well tolerated with no significant difference in the number of adverse events, and this is reflected by similar patient preference for ondansetron (40%) and dexamethasone (30%) (p = 0.244). Both drugs offer adequate out-patient control of chemotherapy-induced emesis; however, dexamethasone has an advantage in the control of delayed nausea, and also in terms of cost and resource allocation.

Acute Disease↗
PubMed1991

Immune modulation and cancer.

The concept that the immune system is involved in defence against cancer goes back nearly a hundred years. Despite increased sophistication in our analysis of the immune response it has proven difficult to demonstrate a powerful role of the immune system in either the prevention or treatment of cancer. Animal data has consistently and clearly shown that the immune system can identify and reject experimental tumours. In patients the data is more conflicting. The isolation of individual cytokines which stimulate specific components of the immune response and have a anti-cancer effect does suggest, however, that as we learn more about the interaction between immunity and cancer, novel methods for the diagnosis and therapy of cancer will be developed.

Antigens, Neoplasm↗
PubMed1991

New therapeutic modalities for cancer.

A review is given on new biological approaches to cancer therapy based on knowledge concerning interferons, interleukins. LAK-cells, tumour-infiltrating lymphocytes, tumour necrosis factor, colony-stimulating factors, monoclonal antibodies and oncogenes. There are many potential permutations for the application of biological therapy for cancer. One of the most important developments has been the increased understanding of the molecular mechanisms of malignancy through which biological manipulation can be tailored to an individual tumour. Although current clinical studies are not demonstrating high response rates they may well be analogous to the advances seen with chemotherapy in its early days. As yet only relatively small numbers of patients have had access to, or been suitable for, treatment. With further refinements in production, administration, and an increase in the specificity of treatment, the possibility of curing metastatic solid tumours may become a reality.

Antibodies, Monoclonal↗
PubMed1991

Preoperative radiotherapy combined with resection of squamous cell carcinoma of the mid-thoracic oesophagus. Does a histopathological malignancy grading system assess actual survival?

The aim of our study was to assess the reproducibility of the findings of Hambraeus et al. In their group of patients with squamous cell carcinoma of the oesophagus who underwent preoperative radiotherapy and resection, the histopathological malignancy grading score system was found to predict survival. We studied nine patients with squamous cell cancer of the mid-thoracic oesophagus, who had received radiotherapy followed by surgery and survived over 12 months. We did not confirm the prognostic value of the histopathological malignancy grading score system.

Aged↗
PubMed1990

The partial purification and characterization of GnRH-like activity from prostatic biopsy specimens and prostatic cancer cell lines.

We have investigated the possibility of the secretion of gonadotrophin-releasing-hormone (GnRH)-like peptides by prostatic cancer cells in culture and their presence in cytosolic preparations from human prostatic biopsy specimens. A GnRH-specific radioimmunoassay showed GnRH-like activity in concentrated cytosolic preparations and conditioned media from DU 145, an androgen-insensitive human prostatic cell line and from LNCaP, an androgen-responsive prostatic cancer cell line. GnRH immunoreactivity in culture media correlated directly with cell numbers. HPLC demonstrated that this GnRH-like material co-migrated with synthetic GnRH. This homology between synthetic GnRH and partially purified prostatic GnRH was confirmed following V8 protease and trypsin digestion which resulted in similar alterations in HPLC characteristics. The mean content of GnRH-like activity/g specimen tissue was significantly more in malignant tissue (88.5 +/- 80.5 fmol) than in benign (29.6 +/- 22 fmol), though more specimens of benign tissue were positive (37/54) than malignant tissue (6/22). This observation, taken with an earlier finding of GnRH-specific receptors in a hormone-sensitive cell line and human cancer specimens provides supportive evidence for the autocrine hypothesis of cell regulation.

Gonadotropin-Releasing Hormone↗
PubMed1990

Oncoprotein stability after tumour resection.

The means by which oncogenes and their products activate malignant transformation are currently under intense investigation. However, published papers on experiments using human tumour material do not always report in detail their methods of collection or storage of the specimens. In order to assess the stability of oncogene encoded proteins following collection or storage of human tumour biopsies, we have examined the rate of decay of the c-myc, neu and EGF-receptor proteins. Solid tumours, containing amplified copies of each oncogene, were established in nude mice and the stability of the oncogene protein in portions of each tumour, left in phosphate buffered saline at room temperature for varying time intervals, was examined by immunoblotting. Intact EGF-receptor and neu oncoproteins were present even after 24 h under these conditions while the c-myc protein was apparently rapidly degraded after 20 min. These data demonstrate that oncogene products decay at different rates after tumour resection and that collection of human biopsies should take this into account in order to provide the basis for consistent measurements of protein expression.

Animals↗
PubMed1990

The effects of gonadotrophin releasing hormone analogues in prostate cancer are mediated through specific tumour receptors.

We have investigated the possibility of a direct regulatory effect of gonadotrophin releasing hormone (GnRH) analogues on prostatic cancer cell growth. Here we report high affinity binding (Kd = 50 nM) of a GnRH analogue resulting in biphasic growth modulation of the human androgen-sensitive prostatic cancer cell line LNCaP. In contrast, the human androgen-insensitive prostatic cancer cell line DU145 showed low-affinity (Kd = 10 microM) binding without any biological response to the GnRH analogue. A GnRH-specific radioimmunoassay demonstrated GnRH-like immunoreactivity in the concentrated culture medium from both cell lines. Seventy-six human benign and malignant tumours were assayed following surgical resection. Nineteen of 22 (86%) malignant tumours and 49 of 54 (91%) benign tumours, exhibited high affinity GnRH-analogue binding. Fourteen of 19 (74%) malignant tumours and 17 of 49 (35%) benign tumours exhibiting high affinity binding contained GnRH-like immunoreactivity, suggesting that this system may be involved in prostatic epithelial cell growth in vivo.

Buserelin↗