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Biomedical subjects

G C Howard

Publications and source records attributed to G C Howard.

At least 55 records · Page 3Linked to original sources

Surgery following chemotherapy for metastatic testicular teratoma.

Twenty patients with metastatic testicular teratoma underwent surgery for residual disease after chemotherapy. Twelve patients in whom complete excision of all residual masses was possible are alive with no evidence of disease. Four patients have died of malignant teratoma, 2 have active malignant disease and 2 have inoperable residual cystic disease. Patients with malignant teratoma intermediate (MTI) primary testis tumours, and those with bulky abdominal disease at presentation, are more likely to have residual masses requiring excision. Completeness of excision appears to be the most important predictor of disease-free survival.

Adolescent↗

Low dose bleomycin with etoposide and cisplatin for metastatic testicular teratoma.

Thirty-nine men with metastatic testicular teratoma were treated with a combination of bleomycin, etoposide and cisplatin (BEP). Unlike the usual regimen of these 3 agents, bleomycin and cisplatin were given on day 1 only of the cycle, with etoposide for 3 days. Thirty patients (77%) are alive and disease-free after a median follow-up of 31 months--24/25 (96%) with disease confined to lymph nodes but only 6/14 (43%) patients with lung involvement. Modified BEP chemotherapy is a well tolerated alternative to standard BEP chemotherapy for small volume nodal disease; it minimises in-patient time, hospital visits and the risk of bleomycin lung toxicity. However, omission of the weekly doses of bleomycin and shortening of the administration schedule of cisplatin and etoposide may be detrimental in patients with more extensive disease, for whom more intensive therapy may be necessary.

Antineoplastic Combined Chemotherapy Protocols↗

Neoadjuvant chemotherapy with methotrexate and cisplatin prior to radiotherapy for invasive transitional cell carcinoma of the bladder. Assessment of feasibility and toxicity.

A prospective study has been performed to assess the feasibility and toxicity of administering neoadjuvant chemotherapy with methotrexate (200 mg/m2) and cisplatin (100 mg/m2) prior to radical radiotherapy. Twenty patients with advanced transitional cell carcinoma of the bladder were assessed after each of 3 courses of chemotherapy, after radiotherapy and 6 months following treatment. Of particular concern was whether neoadjuvant chemotherapy compromised the ability to give potentially curative radical radiotherapy, delayed effective palliation of distressing urinary symptoms, or allowed local tumour progression prior to definitive treatment. It was concluded that this chemotherapy regimen was well tolerated, did not compromise the ability to give radical radiotherapy and resulted in the prompt palliation of urinary symptoms. This treatment, however, did not stop the development or progression of metastatic disease in some patients. In only 1 patient was there local progression during chemotherapy.

Adult↗

Has hyperthermia a place in cancer treatment?

Long before ionising radiations were discovered, attempts were made to exploit elevated temperatures to control malignant tumours. At irregular intervals over the last 100 years, hyperthermia has been suggested for use in cancer therapy but has never become established. There is little doubt that heat alone can destroy tumours; and it can enhance the anti-cancer effects of radiation and chemotherapeutic agents. Laboratory and in vivo animal data provide hyperthermia with a strong biological rationale, which gives the more recent revival of interest a sounder base than previously. The exact science of hyperthermia, however, is still in its infancy, and how it should be employed to its best advantage in human cancer therapy remains illusive. We review the current position of hyperthermia in clinical cancer management and look to see what achievements are likely in the near future.

Humans↗

Carcinoma in-situ of the testis diagnosed on semen cytology.

The case is reported of a patient who presented to an infertility clinic following extensive treatment for testicular teratoma. An incidental finding on semen analysis was of abnormal cells suggestive of carcinoma in-situ. This diagnosis was later confirmed by biopsy of the remaining testicle. Radiotherapy will be given to the testis to ablate the germinal epithelium while sparing Leydig cell function.

Adult↗

Regional hyperthermia for extensive pelvic tumours using an annular phased array applicator: a feasibility study.

Twenty patients with extensive pelvic tumours have been treated with radiotherapy and regional hyperthermia using an annular phased array applicator (APA). The majority of patients had bulky disease with a mean tumour volume of 206 cm3. In 63 of 67 attempted treatments heating was achieved, temperatures in excess of 42 degrees C being reached in the pelvis in 78%. Heat doses, however, were low, only 41% of treatments exceeding 5 min equivalent at 43 degrees C. Treatment was usually limited by acute toxicity and, although this was marked, it was of short duration and no long-term sequelae have been noted. With gain in operator experience, later treatments have achieved improved thermal doses. Response was difficult to assess but we have documented responses in six of 12 assessable patients. Palliation has been achieved in all patients with symptoms. Preliminary attempts to shift the region of maximum heating by phase variations in the APA output are promising, and this technique should improve the quality of treatments and reduce toxicity. The APA is thus capable of inducing pelvic regional hyperthermia, and a randomised controlled study is now planned to assess the value of pelvic hyperthermia as a treatment modality.

Adult↗

A clinical microwave hyperthermia system with multipoint real-time thermal dosimetry.

A clinical hyperthermia system using a 915 MHz microwave generator and incorporating multipoint thermocouple thermometry is described. Temperatures can be monitored simultaneously at 16 points and measurements displayed on a visual display unit and a plotter. The power output of the generator is adjusted under computer control to maintain a constant predetermined temperature in a chosen control channel. A clinically useful feature of the system is the ability to determine the effective cumulative thermal dose delivered to the tissue at points monitored in real time. The basis for the thermal dose calculation is discussed in detail. The calculated dose parameter is displayed for each of the 16 channels during the treatment and updated every 30 s. This real-time display of a thermal dose parameter has made possible a more homogeneous heating of tumours.

Animals↗

Drosophila DNA topoisomerase I is associated with transcriptionally active regions of the genome.

The distribution of DNA topoisomerase I within Drosophila polytene chromosomes was observed by immunofluorescent staining with affinity-purified antibodies. The enzyme is preferentially associated with active loci, as shown by prominent staining of puffs. The heat shock loci 87A-87C are stained after, but not before, heat shock induction. A detailed comparison of the distribution of topoisomerase I with that of RNA polymerase II reveals a similar, although not identical, pattern of association. Topoisomerase I is also found in association with the nucleolus, the site of transcription by RNA polymerase I.

Animals↗

Pancoast's syndrome.

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Evaluation Studies as Topic↗

Non-random position of the A-T rich DNA sequences in early embryos of Drosophila virilis.

Examination of early embryos of Drosophila virilis by light and electron microscopy has shown that the A-T rich satellite DNA sequences have a non-random distribution within the nuclei. As observed by 33258 Hoechst staining and fluorescent microscopy, these sequences are consistently found to be located on the sides of the nuclei nearest to the vitelline membrane. This arrangement of the A-T rich sequences has been observed from the syncytial balstoderm stage into the gastrula stage where, in each nucleus, the satellite DNA sequences remain at a point nearest the topological outside of the organism.

Adenosine↗

Monoclonal antibodies against a specific nonhistone chromosomal protein of Drosophila associated with active genes.

Hybridomas secreting monoclonal antibodies have been produced by fusion of NS-1 mouse myeloma cells with the spleen cells of mice inoculated with a 60-65,000-mol wt fraction of proteins released from Drosophila embryo nuclei treated with DNase I. The antibodies secreted by the hybridomas were examined with polytene chromosomes of formaldehyde-fixed salivary gland squashes by an immunofluorescence assay. Most of the clonal antibodies obtained resulted in specific staining of the chromosomes relative to the cytoplasmic debris. In the case of clone 28, the antibodies showed a preferential association with sites of gene activity, both puffs and loci identified as puffing at some time during the third instar and prepupal period. In larvae that were heat shocked (exposed to 35 degrees C for 15 min before removal and fixation of the glands), the antibodies of clone 28 stained preferentially the induced heat-shock loci while continuing to stain most of the normal set of loci. The antigen for clone 28 was identified as a single protein of approximately 62,000 mol wt by using the antibodies followed by 125I-rabbit anti-mouse Ig to stain nitrocellulose replicas of SDS polyacrylamide gels of total chromosomal proteins. This study demonstrates that monoclonal antibodies can be used successfully in immunofluorescence staining of formaldehyde-fixed polytene chromosomes. The results verify the hypothesis that a specific nonhistone chromosomal protein is preferentially associated with the set of loci that includes both active sites and those scheduled to be active at some time in this developmental program. Such proteins may play a general role in the mechanisms of cell determination and gene activation.

Animals↗

Distribution studies on polytene chromosomes using antibodies directed against hnRNP.

The distribution of nuclear ribonucleoprotein (hnRNP) particles in Drosophila polytene chromosomes has been investigated using anti-B-36 serum as a probe. The use of polytene chromosomes allows resolution at the level of the chromomere, and provides the opportunity to look for both positive and negative correlations with transcriptional activity. The antiserum was obtained using the nuclear protein B-36 from Physarum polycephalum as the immunogen. It has been shown to precipitate hnRNP particles from HeLa cells through a cross-reaction with the major 32,000- and 34,000-dalton hnRNP particle proteins. The antiserum cross-reacts with a Drosophila nuclear protein of approximately 34,000 daltons. By indirect immunofluorescence, we observed that the antiserum reacts preferentially with transcriptionally active loci of the polytene chromosomes, whereas loci previously or subsequently active do not show significant fluorescence. The overall pattern of fluorescence is very similar to that generated with anti-RNA polymerase B serum. The correlation of fluorescence and transcriptional activity observed suggests that the anti-B-36 serum is recognizing hnRNP proteins which have combined with nascent RNA molecules at the sites of transcription.

Animals↗