PubMed HealthSearch

Biomedical subjects

C Rose

Publications and source records attributed to C Rose.

At least 37 records · Page 2Linked to original sources

A novel antigen defined by monoclonal antibody CR101 is associated with small cell lung carcinoma.

Small cell lung carcinoma (SCLC) represents about 25% of all lung cancers. Human SCLC shows neuroendocrine features such as the production of neural peptide hormones, marker enzymes and neurosecretory granules, and the expression of neural cell adhesion molecules (NCAMs). Although SCLC is sensitive to both chemotherapy and radiation, prognosis remains poor due to the appearance of post-treatment chemo- and radioresistant variants. Monoclonal antibodies (MAbs) have been developed that bind to SCLC tumor antigens. We have used similar technology to define another SCLC marker designated gP94/115. The MAb CR101 binds to a highly glycosylated, cell-surface antigen associated with SCLC. In vitro expression of the antigen appears to be restricted to cell lines of SCLC origin. Enzymatic removal of the sugars resolves the antigen into two proteins of 94 and 115 kD by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Fluorescence-activated cell sorting (FACS) analysis confirms the antibody's specificity. These results indicate that CR101 may recognize a novel protein expressed by SCLC.

Animals

The construction and characterization of poliovirus antigen chimeras presenting defined regions of the human T lymphocyte marker CD4.

Defined regions of the CDR2-like region of the T cell antigen CD4 that are implicated in the binding of the surface glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1) to CD4+ T lymphocytes have been engineered in place of antigenic site 1 of Sabin type 1 poliovirus. The antigenic properties of the recovered chimeric virus particles were investigated using monoclonal antibodies (MAbs) and polyclonal serum to CD4. None of the MAbs tested neutralized the chimeras, presumably because they are directed against conformational determinants of the V1 domain of CD4. In contrast, the three antigen chimeras were neutralized by polyclonal serum to CD4, which suggested that the CD4-derived sequences were presented in a relevant conformation. A panel of six MAbs were raised against one of the chimeras, and the epitopes were mapped by the selection of neutralization-resistant mutants and cross-neutralization studies. Five of the six MAbs reacted with soluble CD4 (sCD4) in ELISA, and one (MAb 1686) bound to CD4 expressed at the surface of HeLa cells. The high affinity interaction between gp120 and sCD4 was not blocked by MAb 1686, and the poliovirus-CD4 chimeras did not interact with gp120. These results demonstrate that poliovirus can be used as an epitope expression vector for the presentation of sequences in an immunodominant location on the virus particle which adopt a native or near-native conformation, and supports the findings of previous studies involving the presentation of epitopes derived from pathogens.

Amino Acid Sequence

Crouzon syndrome is not linked to craniosynostosis loci at 7p and 5qter.

Evidence for linkage has been sought, in four pedigrees with Crouzon syndrome, between polymorphic markers known to be linked to the Saethre-Chotzen locus on 7p and another form of autosomal dominant craniosynostosis on 5q. The data we present exclude Crouzon syndrome as an allelic variant at either of these known craniosynostosis loci.

Chromosomes, Human, Pair 5

Bioaerosols.

Explore the source record for details and available documents.

Aerosols

Treatment with very low-dose GM-CSF in myelodysplastic syndromes with neutropenia. A report on 28 cases.

We treated 28 cases of myelodysplastic syndrome (MDS) with neutropenia by very low-dose GM-CSF (0.25 or 0.5 micrograms/kg/day). Median age was 69 years. Nine patients had RA, 18 had RAEB, and one had RARS. Eighteen patients had absolute neutrophil counts (ANC) < or = 0.5 x 10(9)/l, and ten had ANC between 0.5 and 1.0 x 10(9)/l. Ten patients had experienced > or = WHO grade II infection(s) during the preceding 3 months. Eighteen patients (64%) had a response (i.e. ANC at least doubled and > or = 1 x 10(9)/l after 1 month), including 4/8 patients treated at 0.25 mu/kg/day, and 14/20 treated at 0.5 microgram/kg/day (difference not significant). Two of the non-responders obtained a response after dose escalation to 0.5 and 1 microgram/kg/day, respectively. The only prognostic factor of response was FAB subtype (10/11 responses in patients with RA or RARS, vs. 8/17 in RAEB, p = 0.04). Patients with ANC < or = 0.5 x 10(9)/l had a 55% (10/18) response rate, which was not significantly lower than the 80% (8/10) response rate observed in patients with ANC > 0.5 x 10(9)/l. Side-effects were generally moderate, except in three patients where the drug had to be discontinued, including the only patient who progressed to AML. In responders, GM-CSF was continued during 2 to 14 months (median 6), and the response persisted in all but one case, who relapsed after 60 days of treatment. During follow-up, only one responder had > or = WHO grade II infections, as compared to five of the non-responders (of whom two had fatal infectious episodes). In conclusion, very low-dose GM-CSF can durably increase ANC in about two thirds of MDS with neutropenia. Although it remains to be shown in randomized trials that it can reduce the incidence of infections and improve survival in MDS, very low-dose GM-CSF may be an interesting approach in MDS, associated to reasonable cost.

Aged

Information for cancer patients entering a clinical trial--an evaluation of an information strategy.

Informing patients before the start of antineoplastic treatment is important due to the anxiety and uncertainty felt by the patients and the legal aspects of trials. 34 women were interviewed 3 months after receiving information. Results show that the information was well remembered, patients were glad to bring a relative, two consultations with time for deliberation were well-received and that patients viewed written information as an important reinforcement. Overall, information provided was positively evaluated. Detailed information allowed patients to understand and participate in treatment decisions, thereby reducing their pretherapy anxiety. These results support expansion of the structured information programme to include all patients about to begin long-term cancer therapy.

Adult

Adjuvant radiotherapy and risk of contralateral breast cancer.

BACKGROUND: The risk of contralateral breast cancer is increased twofold to fivefold for breast cancer patients. A registry-based cohort study in Denmark suggested that radiation treatment of the first breast cancer might increase the risk for contralateral breast cancer among 10-year survivors. PURPOSE: Our goal was to assess the role of radiation in the development of contralateral breast cancer. METHODS: A nested case-control study was conducted in a cohort of 56,540 women in Denmark diagnosed with invasive breast cancer from 1943 through 1978. Case patients were 529 women who developed contralateral breast cancer 8 or more years after first diagnosis. Controls were women with breast cancer who did not develop contralateral breast cancer. One control was matched to each case patient on the basis of age, calendar year of initial breast cancer diagnosis, and survival time. Radiation dose to the contralateral breast was estimated for each patient on the basis of radiation measurements and abstracted treatment information. The anatomical position of each breast cancer was also abstracted from medical records. RESULTS: Radiotherapy had been administered to 82.4% of case patients and controls, and the mean radiation dose to the contralateral breast was estimated to be 2.51 Gy. Radiotherapy did not increase the overall risk of contralateral breast cancer (relative risk = 1.04; 95% confidence interval = 0.74-1.46), and there was no evidence that risk varied with radiation dose, time since exposure, or age at exposure. The second tumors in case patients were evenly distributed in the medial, lateral, and central portions of the breast, a finding that argues against a causal role of radiotherapy in tumorigenesis. CONCLUSIONS: The majority of women in our series were perimenopausal or postmenopausal (53% total versus 38% premenopausal and 9% of unknown status) and received radiotherapy at an age when the breast tissue appears least susceptible to the carcinogenic effects of radiation. Based on a dose of 2.51 Gy and estimates of radiation risk from other studies, a relative risk of only 1.18 would have been expected for a population of women exposed at an average age of 51 years. Thus, our data provide additional evidence that there is little if any risk of radiation-induced breast cancer associated with exposure of breast tissue to low-dose radiation (e.g., from mammographic x rays or adjuvant radiotherapy) in later life.

Adult

Factors influencing women to undergo screening mammography.

Despite the fact that mammography is a valuable tool for early detection of breast cancer, the majority of age-eligible American women do not avail themselves of screening mammography. To better understand why women do or do not undergo mammography and to further develop guidelines for promoting breast cancer screening, the authors investigated what impact personal factors, attitudes, and health-related behaviors have on compliance with screening mammography by surveying 521 women for information related to health behavior, health concerns, sense of well-being, satisfaction with health care, and knowledge about breast cancer. Women who underwent mammography were more likely to have a regular physician, to practice breast self-examination, to be less concerned over the cost of mammography, to be generally satisfied with their health care, to believe they have a greater sense of control over their health, and to be more knowledgeable about mammography and breast cancer. Age, health behavior, sense of well-being, locus of control, and breast cancer experience helped differentiate between women who had undergone mammography and those who had not.

Adult

Cytotoxic treatment of metastatic breast cancer. Which drugs and drug combinations to use?

Although the optimal efficacy of cytotoxic therapy plateaued in the 1970s, no consensus yet exists regarding which cytotoxic combination to offer as first-line therapy for metastatic breast cancer. Comparison of a combination of CAF/CEF with other cytotoxic combinations reveals that an anthracycline-containing regimen not only increases response rate, but also improves time to progression and survival. Regarding appropriate duration of cytotoxic therapy, randomized trials indicate that therapy in excess of 6 months is beneficial. Although the main objective of cytotoxic therapy in patients with metastatic disease is to palliate symptoms at the least toxic cost, the finding that adjuvant cytotoxic therapy improves survival provides a clinical and ethical rational for continued research into new drugs and combinations in the hope that new strategies can be employed not only against metastatic breast cancer but may be applied with benefit also in the adjuvant situation.

Antineoplastic Agents

Weekly oral idarubicin in advanced prostatic cancer. A phase II study.

Twenty-five patients with advanced prostatic cancer progressing after one course of endocrine treatment entered a phase II study of weekly administration of 30 mg Idarubicin orally. Twenty-two patients were evaluable for response and partial response (PR) was noted in 2 patients and stable disease (NC) in 10 patients. Median survival was 31 weeks and median time to progression was 14 weeks. Twenty-three patients were eligible in a score system combining analgetic consumption and pain reduction measured on a Visual Analogue Scale (VAS) and 30% achieved a subjective response. Fifteen patients fulfilled treatment with the planned dose and 10 patients had dose reduction to a median of 23.8 mg Idarubicin. Haematological toxicity was greater than or equal to grade 3 (WHO) in 20% of the patients. Non-haematological toxicity was dominated by nausea/vomiting with 48% grade 3 (WHO). In conclusion, Idarubicin seems of limited value in the treatment of patients refractory to first line endocrine treatment.

Administration, Oral

Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish Breast Cancer Cooperative Group.

The Danish Breast Cancer Cooperative Group (DBCG) conducted a randomized trial comparing breast conservation with mastectomy in patients with invasive mammary carcinoma. From January 1983 to March 1989, the trial accrued a total of 1153 women. Of this number, 905 patients (79%) were randomly assigned to one of the two treatment options, whereas 248 patients (21%) did not accept randomization. Of the randomly assigned patients, 90% received the surgical option to which they had been originally assigned. In the breast conservation arm the tumor was excised with the intention of obtaining free margins determined at gross examination, and radiotherapy was subsequently administered to residual breast tissue. The axilla was dissected in all instances. Patient and tumor characteristics were similar in the two randomization arms. The median follow-up time was 40 months. At 6 years of life-table analysis the probability of recurrence-free survival was 70% in the breast conservation arm against 66% in the mastectomy arm. Survival figures were 79% against 82%, respectively.

Breast Neoplasms

[Adjuvant endocrine treatment of postmenopausal patients with breast cancer with high risk of recurrence. 5. Results from the DBCG (Danish Breast Cancer Cooperative Group) 77C randomized trial].

The role of antiestrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective trial conducted by the Danish Breast Cancer Cooperative Group (DBCG). After total mastectomy and postoperative radiotherapy (RT), 840 patients were randomized to treatment with tamoxifen (RT + TAM) for one year, and 824 were randomized to no further therapy (RT). The recurrenceree survival (RFS) after ten years of lifeable analysis is 31% in the RT + TAM treated group, and 28% in the RT group (p = 0.01). Survival is 38% and 34% in the two treatment groups, respectively (p = 0.04). The data were further analyzed with respect to prognostic factors such as age, number of positive nodes, tumour size, and degree of anaplasia. Survival is prolonged in nearly all subgroups of patients treated with RT + TAM. However, the prolongation is only significant in patients with four or more positive nodes, with tumours of less than 5 centimeters or with tumours of anaplasia grade II. Estrogen (ER) and progesterone receptor (PgR) concentrations were measured in tumours from 309 and 219 patients, respectively. Only patients with ER and PgR values above 100 fmol/mg cytosol protein seemed to have a prolongation of survival. In conclusion, a modest survival benefit is achieved with one year of adjuvant tamoxifen treatment. Nevertheless, this is the first example of a systemic treatment approach being able to change the fatal course of breast cancer in postmenopausal patients. By means of endocrine therapy, and in the context of a new randomized trial, the DBCG will try to improve the survival in these patients even further.

Aged

[Shark liver oil (alkoxyglycerol) and cancer treatment].

Alkoxyglycerol derived from shark liver oil is marketed in Denmark and mentioned in popular articles as a supplementary agent in the treatment of cancer. A questionnaire investigation carried out in the Department of Oncology and Haematology in Odense Hospital revealed that approximately 1/3 of the patients in active neoplastic therapy employed shark liver oil preparations. The clinical investigations of alkoxyglycerol were all carried out on patients with cancer of the uterine cervix. All of the investigations were carried out by the same Swedish research group. Only a minority of the experimental material was blinded. No documentation was found for inhibited tumour growth or reduced mortality resulting from treatment with alkoxyglycerol. The number of cases of irradiation damage were found to be fewer in the groups treated with alkoxyglycerol, but the difference may be partially explained by different subdivision into stages. Alkoxyglycerol results in increase in the leukocyte and thrombocyte counts while higher or lower doses have, apparently, the opposite effect. The available literature concerning the clinical effect of alkoxyglycerol is limited and unsystematic and does not support the employment of alkocyglycerol in the treatment of cancer.

Animals