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Biomedical subjects

K Sikora

Publications and source records attributed to K Sikora.

At least 55 records · Page 3Linked to original sources
PubMed1994

Genes, dreams, and cancer.

There have been tremendous advances in our understanding of cancer from the application of molecular biology over the past decade. The disease is caused by a series of defects in the genes that accelerate growth--oncogenes--and those that slow down cellular turnover--tumour suppressor genes. The proteins they encode provide a promising hunting ground in which to design and test new anticancer drugs. Several treatment strategies are now under clinical trial entailing direct gene transfer. These include the use of gene marking to detect minimal residual disease, the production of novel cancer vaccines by the insertion of genes which uncloak cancer cells so making them visible to the host's immune system, the isolation and coupling of cancer specific molecular switches upstream of drug activating genes, and the correction of aberrant oncogenes or tumour suppressor genes. The issues in these approaches are likely to have a profound impact on the management of cancer patients as we enter the next century.

Gene Transfer Techniques↗
PubMed1994

Combined choriocarcinoma and yolk sac tumor arising in Barrett's esophagus.

A patient with primary adenocarcinoma with yolk sac and trophoblastic differentiation occurring in Barrett's esophagus is reported. Yolk sac differentiation at this site has not been described previously. The diagnosis of germ cell differentiation initially was suggested by the finding of elevated serum tumor marker levels. The patient experienced disease remission after cytotoxic chemotherapy. Germ cell differentiation may be difficult to identify in small biopsy samples, which may not be representative of the tumor as a whole. The finding of germ cell differentiation defines therapy and predicates for a relatively good prognosis, which is contrast to adenocarcinoma. Because of the significance of germ cell differentiation in the selection of appropriate therapy, immunostaining for germ cell tumor markers is suggested in all patients with adenocarcinoma who are younger than 50 years.

Adenocarcinoma↗
PubMed1994

Enraged about radiotherapy.

The use of radiotherapy in treating breast cancer has meant that many women are able to avoid mastectomy, which is both physically and psychologically damaging. The side effects of radiotherapy, however, are given little attention. Many women have developed brachial plexus injury after radiotherapy for breast cancer, often resulting in severe pain and loss of use of the arm. There is no effective treatment for this injury and little help can be offered. In addition, many of the women did not require radiotherapy of nodal areas. A pressure group has been formed to support these women, to establish the right to compensation, and to ensure that radiotherapy regimens given to future patients will not damage the brachial plexus.

Brachial Plexus↗
PubMed1994

Gene therapy for cancer using tumour-specific prodrug activation.

Current treatments for metastatic malignant disease are often ineffective. One of the most promising of the selective genetic strategies against cancer is VDEPT (virally directed enzyme prodrug therapy). This uses a viral vector to carry a prodrug-activating enzyme gene into both tumour and normal cells. By linking the foreign gene downstream of tumour-specific transcription units, tumour-specific expression of the foreign enzyme gene can be achieved. We have developed a genetic therapy strategy using VDEPT against cancers that overexpress the oncogene ERBB2. This occurs in approximately one-third of breast and pancreatic tumours (and in a smaller proportion of other tumours) and involves transcriptional up-regulation of the ERBB2 gene with or without gene amplification. We have constructed a chimeric minigene consisting of the proximal ERBB2 promoter linked to the gene encoding cytosine deaminase, an enzyme that can deaminate the prodrug 5-fluorocytosine (5-FC) to form cytotoxic 5-fluorouracil (5-FU). We have constructed a double-copy recombinant retrovirus to deliver the enzyme gene under the control of the ERBB2 promoter into a panel of ERBB2 expression-positive (ERBB2+) and -negative (ERBB2-) pancreatic and breast cell lines. Cytosine deaminase activity was high in ERBB2+ transduced cells but was not detected in ERBB2- transduced cells. Significant cell death was observed in ERBB2+ transduced cells treated with 5-FC whereas ERBB2- cells were not affected. Hence we present a novel gene therapy strategy that is potentially tumour-specific and could be used against a range of tumour types that overexpress the ERBB2 oncogene.

Base Sequence↗
PubMed1993

Multidrug resistance and behavioural phenotype of cancer cells.

Resistance to cytotoxic chemotherapy is a major obstacle preventing successful treatment of cancer, allowing dissemination of tumour metastases, and may be viewed as the ultimate cause of death in the majority of patients with a malignant disease. Although cytotoxic chemotherapy is classically employed to produce maximal killing of malignant cells, the therapeutic doses of individual drugs required to achieve this objective are, in general, highly toxic to non-neoplastic host tissues. However, there are several different aspects of cancer cell biology, distinct from their susceptibility to cytotoxicity, that might be exploited in order to alter the behavioral phenotypes of malignant neoplasms. Such features include regulation of cell proliferation, tumorigenicity and metastatic potential. Non-cytotoxic modulation of malignant cells may provide an alternative, and more effective, method of controlling the aggressive behaviour of cancer cells while exhibiting less iatrogenic morbidity and mortality than the therapeutic regimens presently employed.

Animals↗
PubMed1993

Complementary and conventional cancer care: the integration of two cultures.

There is now increasing evidence that many cancer patients are seeking unorthodox forms of support and treatment. These range from measures to enhance the quality of life, such as counselling and relaxation therapy, through to alternative cancer remedies, such as extreme diets with detoxification by coffee enemas. Much of complementary care is provided outside the hospital setting, often without the knowledge of the health care professionals involved in a patient's treatment. The Bristol Cancer Help Centre was founded in 1980 to provide an alternative approach to cancer treatment. It became the leading British centre for such therapies, although, from its outset, it had an uneasy relationship with conventional medicine. Some clinicians were highly critical of its perceived methods even though very few actually visited the centre to examine the evolving programmes of care offered. In 1988, a group of oncologists from Hammersmith Hospital visited the Bristol Centre. A joint development programme was conceived in which the lessons from Bristol were integrated into a busy academic oncology unit prior to the design and construction of a new cancer centre. Many problems emerged in trying to merge the two cultures, one driven by technology, the other by human need. Several other oncology units are adopting complementary strategies within their services. Here we describe our joint experience and outline the Hammersmith supportive care model currently in use.

Complementary Therapies↗
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↗