Radioresistant tumor cell lines derived from head and neck radiation failures.

We studied the in vitro radiobiological parameters of 16 human head and neck squamous cell carcinoma tumor cell lines cultured from patients who suffered local failure after a curative course of radiotherapy. The radiobiological parameters determined included D0, n, and D. When compared with in vitro radiobiological parameters of tumor cells cultured from head and neck cancer patients prior to radiotherapy, human sarcoma cell lines, and normal human diploid fibroblasts studied in our laboratory (as well as other human tumor cell lines reported in the literature), tumor cells derived from radiotherapy failures on average are resistant to the cytotoxic effects of ionizing radiation.

Effect of antisense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous carcinoma.

Antisense RNA-mediated inhibition of gene expression was used to investigate the biological function of the c-raf-1 gene in a radiation-resistant human squamous carcinoma cell line, SQ-20B. S1 nuclease protection assays revealed that transfection of full-length raf complementary DNA in the antisense orientation (AS) leads to a specific reduction (greater than tenfold) of steady-state levels of the endogenous c-raf-1 sense (S) transcript in SQ-20B cells. In nude mice, the malignant potential of SQ-20B cells transfected with raf (S) was significantly increased relative to that of SQ-20B cells transfected with raf (AS).

An important step in radiation carcinogenesis may be inactivation of cellular genes.

The loss of genetic material may result in a predisposition to malignant disease. The best studied example is retinoblastoma where deletion or transcriptional inactivation of a specific gene is associated with the development of the tumor. When hereditary retinoblastoma patients are treated with radiation, the incidence of osteosarcoma within the treatment field is extremely high compared to other cancer patients treated with radiotherapy.

Comparative analysis of the inherent radiosensitivity of ovarian carcinoma.

Success or failure of radiation therapy in patients with ovarian carcinoma is due to the inherent radiosensitivity of both the tumor cell and the surrounding normal tissues. The D0 value were 1.65 Gy for benign mesothelium, 1.

In vitro radiobiological parameters of human sarcoma cell lines.

In vitro radiobiologic survival parameters have been determined for 7 human osteosarcoma, 5 human soft tissue and bone sarcomas, and 4 Ewing's sarcoma cell lines. The mean D0 values were 99.5 +/- 11.

X-ray and cis-diamminedichloroplatinum(II) cross-resistance in human tumor cell lines.

Clinical studies have suggested a close correlation between cis-diamminedichloroplatinum(II) (cisplatin) and radiation resistance. To determine whether this cross-resistance is due to an inherent cellular resistance to both agents, ten early passage human tumor cell lines were examined for their radiation and cisplatin sensitivity in vitro. Previous studies have suggested that these early passage tumor cell lines retain many of their in vivo characteristics and are therefore good models for tumor cells in vivo.

Radioresistant tumor cells are present in head and neck carcinomas that recur after radiotherapy.

We determined the in vitro survival parameters of 14 human head and neck squamous cell carcinoma tumor cell lines cultured from patients who suffered local failure after a curative course of radiotherapy. The radiobiological parameters determined included D, D0, n, and surviving fractions at 100, 200, and 300 cGy. When compared to in vitro radiobiological parameters of tumor cells cultured from head and neck cancer patients prior to radiotherapy, human sarcoma cell lines derived from patients not receiving therapeutic radiation, normal human diploid fibroblasts or other human tumor cell lines reported in the literature, the human tumor cells derived from radiotherapy failures are radioresistant.

Successful transcutaneous external pacing for asystole following cardiac arrest.

We report a case of successful transcutaneous external pacing for out of hospital cardiac arrest causing asystole.

Southern analysis of human head and neck cancer cells for homologous sequences using yeast gamma repair genes.

We employed southern analysis to examine homology between yeast genes RAD 51, RAD 52, RAD 54, and RAD 55 for possible gamma repair genes in radioresistant or repair proficient human tumor cell lines and normal placental DNA. No homology wa observed; however, other strategies including further gene restriction and transfection are underway to identify repair genes in human tumors. Understanding mechanisms of radiation repair might lead to more effective clinical radiation treatment protocols.

Synergistic cytotoxicity and DNA strand break formation by bromodeoxyuridine and bleomycin in human tumor cells.

5-Bromo-2'-deoxyuridine (BrdUrd) is a thymidine analogue whose cellular effects are related to its incorporation into DNA. BrdUrd is a known radiosensitizing agent that could potentially enhance the activity of chemotherapeutic agents that interact directly with DNA. Therefore we studied the interaction of BrdUrd and bleomycin in a human head and neck squamous carcinoma cell line, SQ20B.

Heterogeneity of radiation response of a parent human epidermoid carcinoma cell line and four clones.

We examined the radiobiological parameters of a parent tumor cell line and four tumor clones of a human skin squamous cell carcinoma. The parent line and all clones have a tumor morphology, aneuploid karyotype, and the ability to passage infinitely in vitro. The parent cell line and three of four clones formed tumors in nude mice.

Some retinoblastomas, osteosarcomas, and soft tissue sarcomas may share a common etiology.

DNA and RNA were extracted from primary human osteosarcomas and soft tissue sarcomas obtained from patients without retinoblastoma and were analyzed by hybridization with a cDNA probe for RB mRNA; absence or alterations of the RB gene are associated with development of retinoblastoma. Most of the osteosarcomas or soft tissue sarcomas examined by us did not express detectable levels of RB mRNA, whereas normal cells and epithelial tumor cells did. One osteosarcoma expressed a 2.

Deaths in three accident and emergency departments.

A survey of three London hospitals found that approximately 0.45 patients per thousand new attenders die in the accident and emergency department and that there is evidence of poor management in about 10% of these deaths. The commonest faults were excessive delay before starting appropriate treatment and neglect of the basic principles of emergency medicine.

Binding of human IgG to cultured urogenital tumor cells.

Binding of human IgG by the Fc portion of the immunoglobulin molecule was detected on established human tumor cell lines by indirect immunofluorescence microscopy, cytofluorography, quantitative absorption, and rosette formation with the use of antibody-coated erythrocytes. Of the nonlymphoid tumors tested, IgG binding was restricted to the cell membranes of certain prostate and urinary bladder tumor cell lines. Although most cell lines tested shared a common antigenic determinant with monocytes and granulocytes, these cells did not express T- and B-cell antigens, the complement 3b receptor, or bind a monoclonal antibody specific for the Fc receptor expressed on human neutrophils.

The maximum recovery potential of human tumor cells may predict clinical outcome in radiotherapy.

We studied inherent radiosensitivity/resistance (D0), ability to accumulate sublethal damage (n) and repair of potentially lethal damage (PLDR) in established human tumor cell lines as well as early passage human tumor cell lines derived from patients with known outcome following radiotherapy. Survival 24 hrs after treatment of human tumor cells with X rays in plateau phase cultures is a function of initial damage (D0, n), as well as recovery over 24 hrs (PLDR). A surviving fraction greater than .

Severe polyhydramnios: incidence of anomalies.

The sonograms of 195 singleton pregnancies complicated by polyhydramnios were reviewed, and follow-up information was obtained on 191 patients. A grading system was developed that differentiated mild from severe polyhydramnios using real-time or static sonographic equipment. Mild polyhydramnios was present in 138 (71%), and severe polyhydramnios was present in 57 (29%).

Radiation-resistant and repair-proficient human tumor cells may be associated with radiotherapy failure in head- and neck-cancer patients.

Inherent cellular radioresistance and repair of x-ray damage was studied in 19 early-passage squamous cell carcinoma lines derived from head- and neck-cancer patients with known clinical results following radiotherapy. Human tumor cells that were radioresistant and/or proficient in accumulation/repair of x-ray damage were cultured from patients unsuccessfully treated with radiotherapy. Thus, the presence of radiation-resistant and repair-proficient tumor cells was associated with clinical radiation failure, suggesting the possibility of a predictive assay based on in vitro radiobiological parameters.

Human prostate tissue antigens defined by murine monoclonal antibodies.

BALB/c mice were hyperimmunized against a membrane preparation derived from a pool of transurethral resection specimens which included three benign prostatic hyperplasia and one prostate adenocarcinoma tissue samples. The activated lymphocytes were fused with the NS-1 mouse myeloma cell line, and supernatants from immunogen-reactive hybridomas were screened for antibody binding activity using a solid-phase radioimmunoassay against the Calu-1 human lung adenocarcinoma cell line and several membrane preparations derived from various normal human tissues. Hybridoma cultures secreting antibodies which did not appear cross-reactive were doubly cloned by limiting dilution and screened against a large panel of membrane preparations derived from normal prostate, benign prostatic hyperplasia, and prostate adenocarcinoma tissues as well as samples obtained from a variety of normal human tissues.

The vagrant in the accident and emergency department.

Those of no fixed abode constituted only 0.3% of all new patients seen in one year. The majority presented with a disorder due to acute medical illness or trauma.

Antiprostate carcinoma monoclonal antibody (D83.21) cross reacts with a membrane antigen expressed on cytomegalovirus-transformed human fibroblasts.

Virological and epidemiological studies have implicated human cytomegalovirus (HCMV) as a possible etiological agent of prostate cancer. Because of the suspected associations, this laboratory tested the reactivity of a prostate-associated monoclonal antibody with HCMV-transformed cells. This mouse monoclonal antibody, D83.

Immunohistochemical localization of prostate carcinoma-associated antigens.

The immunoperoxidase technique was used to study the localization and distribution of antigens reactive with two monoclonal antibodies, D83.21 and P6.2, produced against cultured prostate tumor cells, in formalin-fixed, paraffin-embedded histological sections of human tissues.

The mesothelial keratins: a new family of cytoskeletal proteins identified in cultured mesothelial cells and nonkeratinizing epithelia.

The cytoskeletal proteins of cultured normal human mesothelial cells were found to consist of six major components, including actin, vimentin, the 40 kd keratin and the 44, 52 and 55 kd proteins, plus a minor 46 kd protein. Two-dimensional gel electrophoresis, peptide mapping and immunoprecipitation tests showed that the 40-55 kd mesothelial proteins are a family of keratins distinct in size, charge or peptide map from the "epidermal keratins" synthesized by cultured keratinocytes. Unique combinations of keratins from the epidermal and mesothelial keratin families were found to be synthesized by cultured bladder, esophageal, conjunctival, mammary, exocervical and ovarian surface epithelial cells.

Monoclonal antibodies to human prostate and bladder tumor-associated antigens.

Monoclonal antibodies to human prostate adenocarcinoma membrane antigens were produced by fusion of P3X63/Ag8 mouse myeloma cells with spleen cells from BALB/c mice immunized against the prostate cancer cell line DU145. The hybrids were screened for antibody production using glutaraldehyde-fixed cells in a solid-phase radioimmunoassay. Antibody-binding specificity was also checked by quantitative adsorption, membrane immunofluorescence, and complement-dependent cytotoxicity assays.