Biomedical subjects

A Dritschilo

Publications and source records attributed to A Dritschilo.

At least 109 records · Page 6Linked to original sources

PubMed1988

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.

Carcinoma, Squamous Cell↗

PubMed1988

Intraoperative interstitial radiation therapy for hepatic metastases from colorectal carcinomas.

Liver metastases from colorectal carcinomas occur frequently. While surgical resection offers the only hope for long-term cure, unsuspected bilobar metastases or extrahepatic metastatic disease may be found at laparotomy, precluding hepatic resection for cure. In this setting intraoperative interstitial hepatic irradiation using the Gamma Med II (Mick Radio-Nuclear Instruments, Bronx, New York) remote afterloading irradiator and an Iridium-192 source permits delivery of a tumoricidal dose to liver tumor(s) with a limited radiation dose to adjacent normal liver. Six patients underwent laparotomy for potential resection of hepatic metastases in a shielded operating room equipped with remote anesthesia monitoring capability and were found to be unresectable. An upper hand retractor facilitated liver exposure during the exploratory and subsequent radiation phases of the procedure. Intraoperative interstitial radiation therapy was performed in each patient. No significant complications occurred on follow-up from 2 to 9 months. Hepatic tumor regression or stabilization occurred on sonography and/or CT scan in each case with a median follow-up of 5 months. The technique offers the potential to ablate discrete tumor nodules within the liver. Ongoing clinical trials will determine the role of intraoperative interstitial radiation in the treatment of hepatic metastases.

Adenocarcinoma↗

PubMed1987

Radiotherapy in the management of pancreatic islet cell tumors.

Malignant islet cell tumors are commonly treated with surgical resection. Chemotherapy is reserved for residual, unresectable, or metastatic disease. The role for radiotherapy has not been clearly defined. This article describes three cases of advanced islet cell tumors treated effectively with radiotherapy. This experience, in addition to that from other published reports, suggests that radiotherapy is a useful mode for treating advanced islet cell carcinoma.

Adenoma, Islet Cell↗

PubMed1987

The raf oncogene is associated with a radiation-resistant human laryngeal cancer.

In order to identify the genetic factors associated with the radiation-resistant human laryngeal carcinoma cell line (SQ-20B), tumor cell DNA was transfected into NIH/3T3 cells. A high incidence (six out of six) of raf sequences was found in transfected NIH/3T3 clones and the tumorigenic potential of SQ-20B DNA could be linked to genomic fragments that represent most of the kinase domain of human c-raf-1. An apparently unaltered 3.5-kilobase pair (kb) human c-raf transcript was identified in SQ-20B cells but was not observed in the transfected NIH/3T3 cell clones. Two new transcripts (4.2 kb and 2.6 kb) were found in tumorigenic clones; the large transcript was missing in a very poorly tumorigenic clone. Cytogenetic analysis indicated that the normal autosomes of chromosome 3 were absent in SQ-20B karyotypes and had formed apparently stable marker chromosomes. Unlike the recipient NIH/3T3 cell line, 30 percent of the transformed clone-1 metaphases had minute and double-minute chromosomes representative of amplified DNA sequences. The frequency of the c-raf-1 identification by NIH/3T3 transfection of SQ-20B DNA suggests the presence of some genetic abnormality within this locus.

Animals↗

PubMed1987

Intraoperative single-dose radiotherapy. Observations on staging and interstitial treatment of unresectable liver metastases.

Fourteen patients with a history of colonic cancer were evaluated for metastatic disease and were thought to have unresectable disease confined to the liver. Exploratory surgery revealed that two patients had extensive extrahepatic disease, and the procedure was terminated. In 12 patients, closed-end needles (diameter, 2.1 mm) were introduced into each nodule and connected to a 370-MBq (10-Ci) afterloading iridium source. Radiation doses were dependent on nodule size, providing minimum doses of 20 Gy (2000 rad) to the lesion's periphery with rapid radiation falloff avoiding toxic effects to adjacent normal tissue. The maximum number of nodules treated in one patient was 11. The largest nodule treated measured 9 x 6.5 x 6 cm. Cholecystectomy in four patients allowed precise implantation and obviated biliary fistula. Preoperative computed tomography underestimated the number of hepatic metastases in all cases but one, and treatment-induced computed tomographic alterations further limited its utility. Radiation treatment was well tolerated, and the median hospitalization was eight days. Of ten patients whose preoperative carcinoembryonic antigen values exceeded 10 ng/dL, the values in six patients decreased postoperatively.

Adult↗

PubMed1987

Dose-volume and complication in interstitial implants for breast carcinoma.

A common radiotherapeutic technique for treating breast cancer is the combination of external beam radiation with an interstitial iridium-192 boost. When smaller tumors (T1 and T2) are treated using this technique, the soft tissue complication rate is small. However, with treatment of more advanced stages of disease, where large volumes of breast tissue must be treated to high radiation doses, the incidence of complication increases. This paper investigates the dose and volume relationships for breast tissue treated by interstitial technique and correlates this to the risk of soft tissue radiation injury. A method of analysis of interstitial radiation implants suitable for intra- or inter-institutional clinical evaluations is offered. The records of 111 patients treated at Georgetown University Hospital, were retrospectively analyzed and the five who had experienced radiation-related complications were compared to 51 randomly selected patients experiencing no complications. The volumes of tissue enclosed by selected isodose surfaces were calculated and used to determine a relationship between these dose-volumes and the probability of complication. The mean volume at specified dose levels between 10 Gy and 50 Gy was significantly higher (p less than .05) for the patients developing complications than those in whom no complications were seen. Using the 20 Gy isodose surface as defining our usual treated volume, a complication probability versus dose-volume curve was developed using a linear logistic model. The curve fitted the data closely (p less than .006) suggesting that, for our cases, the calculated treatment volume (within the 20 Gy isodose surface) can be used to effectively separate patients into groups that have different probabilities of developing complications. We propose this method as a basis for specification of dose and volume which can be used for clinical risk assessment, and for intra- and inter-institutional comparison.

Brachytherapy↗

PubMed1987

Human epidermal keratinocytes retain radiation resistance following in vitro immortalization and malignant transformation.

The radiobiology of human tumors suggests that multiple factors are involved in clinical radioresponsiveness. To date, no direct experimental evidence is available to correlate intrinsic cellular radiosensitivity with the steps of malignant transformation. We developed an in vitro multistage model of epithelial neoplasia using human epidermal keratinocytes to examine the effects of malignant transformation on radiation response. These cells were first immortalized as a result of infection with a hybrid virus (adenovirus 12 and simian virus 40) and subsequently transformed either by infection with a second virus (Kirsten murine sarcoma virus) or by treatment with a chemical carcinogen (N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide). We demonstrate that primary human epidermal keratinocytes were radiation resistant (D0 = 2.24 Gy) as compared with human fibroblasts (D0 = 1.45 Gy) and that this resistance was retained in the immortalized as well as the transformed cell lines. These findings present direct experimental evidence that radiation sensitivity of malignant human keratinocytes is an intrinsic property of the precursor cell that may be conserved through the stages of neoplastic transformation.

Adaptation, Biological↗

PubMed1986

Phase I combined modality clinical trial of alpha-2-interferon and radiotherapy.

Sixteen patients were enrolled in a Phase I study of the combined use of recombinant DNA alpha-2-interferon (IFN) and radiation therapy, conducted at the Georgetown University Hospital (GUH) from February 1, 1984 to September 20, 1985. Escalating IFN doses ranging from 2.0 X 10(6) IU/m2 to 5 X 10(6) IU/m2 were administered to groups of six patients per IFN dose level. Three patients at each dose level were treated on a 5-day-a-week schedule and three patients were treated on a 3-day-a-week schedule. Significant toxicity including dehydration, infection, deep vein thrombosis, and myocardial infarction was noted throughout in patients receiving IFN five times per week, with eight of nine requiring hospitalization during the treatment course. There was one treatment-related death. In the five-times-per-week group, only 22% of patients tolerated the full initially planned IFN dosage and 44% tolerated the full initially planned radiation dosage, compared to 100 and 86%, respectively, in the three-times-per-week group. A tolerance dose and schedule of 5.0 X 10(6) IU/m2 of alpha-2-interferon administered subcutaneously three-times-per-week in conjunction with standard radiotherapy has been identified for use in future combined modality trials.

Combined Modality Therapy↗

PubMed1986

Inhibition of potentially lethal radiation damage repair in normal and neoplastic human cells by 3-aminobenzamide: an inhibitor of poly(ADP-ribosylation).

The effect of 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) synthetase, on potentially lethal damage repair (PLDR) was investigated in normal human fibroblasts and four human tumor cell lines from tumors with varying degrees of radiocurability. The tumor lines selected were: Ewing's sarcoma, a bone tumor considered radiocurable and, human lung adenocarcinoma, osteosarcoma, and melanoma, three tumors considered nonradiocurable. PLDR was measured by comparing cell survival when cells were irradiated in a density-inhibited state and replated at appropriate cell numbers at specified times following irradiation to cell survival when cells were replated immediately following irradiation. 3AB was added to cultures 2 hr prior to irradiation and removed at the time of replating. Different test radiation doses were used for the various cell lines to obtain equivalent levels of cell survival. In the absence of inhibitor, PLDR was similar in all cell lines tested. In the presence of 8 mM 3AB, differential inhibition of PLDR was observed. PLDR was almost completely inhibited in Ewing's sarcoma cells and partially inhibited in normal fibroblast cells and osteosarcoma cells. No inhibition of PLDR was observed in the lung adenocarcinoma or melanoma cells. Except for the osteosarcoma cells, inhibition of PLDR by 3AB correlated well with radiocurability.

Benzamides↗

PubMed1986

Differential radiosensitization of human tumour cells by 3-aminobenzamide and benzamide: inhibitors of poly(ADP-ribosylation).

The effect of 3-aminobenzamide (3AB) and benzamide (BZ) (inhibitors of poly(ADP-ribose) synthetase) on radiosensitivity was investigated in normal human fibroblasts and three human cell lines established from tumours with varying degrees of clinical radiocurability. The human tumour cell lines selected were: Ewing's sarcoma, a bone tumour usually considered radiocurable with moderate radiation doses; lung adenocarcinoma, a tumour considered radiocurable with high doses of radiotherapy; and osteosarcoma, a very resistant tumour which is rarely controlled by standard doses of radiotherapy. Poly(ADP-ribose) synthetase inhibitors were added to cultures 2 h prior to irradiation and removed 24 h after. Inhibitors were used at doses producing little or no toxicity in cells. In the presence of these inhibitors, a differential radiosensitization was observed. Ewing's sarcoma cells and normal human fibroblasts were sensitized to an equal extent by either 8 mM 3AB or 4 mM BZ. However, no sensitization was observed at these concentrations in the lung adenocarcinoma cells or osteosarcoma cells. The degree of radiosensitization in vitro by 3AB and BZ correlates well with the clinical radiocurability of these tumours in vivo.

Benzamides↗

PubMed1986

Relationship between DNA strand breaks and inhibition of poly (ADP-ribosylation): enhancement of carcinogen-induced transformation.

Inhibition of poly(ADP-Rib) by benzamide (BA) or 3-amino-benzamide (3AB) for a limited period (i.e., when ADP-ribosylation is elevated) during and shortly following X-ray or MNNG-induced DNA damage of BALB/3T3 cells significantly (3- to 30-fold) enhanced transformation frequency by these agents. Individual Type III foci isolated from benzamide, X-ray, or X-ray plus benzamide treated cultures were established and characterized for growth in soft agar and for tumor induction in nude mice. DNA isolated from representative transformed lines established as a result of BA, X-ray or X-ray and BA treatments was transfected onto NIH/3T3 cells. Transformation efficiencies ranging from 0.17 to 0.28 foci/micrograms of DNA were observed suggesting the possibility that dominant transforming gene(s) were responsible for the oncogenic phenotype of radiation and benzamide transformed DNA.

Animals↗

PubMed1986

Interstitial radiation therapy for hepatic metastases: sonographic guidance for applicator placement.

A new technique is reported for the treatment of hepatic metastases using sonography-directed percutaneous placement of a 14-gauge needle applicator and a high-intensity "remote afterloading" iridium-192 (Ir-192) source for interstitial radiation therapy. The results with six patients show that the procedure is easily performed, patient tolerance is good, and there is minimal disruption of the patient's lifestyle. Hospitalizations have been less than 24 hr. Partial response or stable disease in the liver was observed in all six patients. Tumoricidal doses up to 5000 rad (cGy) in a single treatment with durations from 7 to 41 min were achieved in small volumes (less than 25 cm3) with no clinically significant toxicity on follow-up evaluations from 2-6 months. The technique appears to ablate discrete metastatic tumor deposits in the liver.

Brachytherapy↗

PubMed1986

The combined use of interferon and radiotherapy in cancer management.

Preclinical studies have suggested combination therapy with interferon and radiation results in an enhanced cytotoxic effect. Both additive and synergistic effects have been reported in mammalian cells in tissue culture. A phase I trial was designed to determine patient tolerance to concomitant Schering interferon alfa-2b (Intron A) and radiation therapy (RT). RT was delivered in standard fashion (five times a week in 180 rad fractions). Interferon was injected subcutaneously 2 hours prior to irradiation. Sixteen patients, divided into groups of three, received interferon at dose levels of 2 X 10(6) to 30 X 10(6) IU/m2 given five or three times a week. Planned dose escalations were stopped at 5 X 10(6) IU/m2 by patient tolerance. We observed a significant difference in tolerance to treatment between the patients receiving interferon three times a week and those receiving interferon five times a week. Eight of nine patients treated five times a week developed grade III-IV toxicity resulting in hospitalization and discontinuation of interferon; radiation was not discontinued. Only two of seven patients treated three times a week were hospitalized, with grade II toxicity (anorexia), but both were subsequently able to continue treatment with both interferon and radiation. We have identified a maximum tolerated dose and schedule of interferon (5 X 10(6) IU/m2 three times a week) for use in future combined modality trials to assess the potential clinical effectiveness of interferon in combination with RT.

Adult↗

PubMed1985

The association of human c-Ha-ras sequences with chromatin and nuclear proteins.

As a step towards the understanding of possible relationship between chromatin organization and regulation of the oncogene expression, we have investigated the chromatin structure of one of the more frequently activated oncogenes, c-Ha-ras, in HeLa-S3 cells. This was accomplished by isolation of the chromatin fractions (soluble and insoluble) after micrococcal nuclease digestion of purified nuclei and probing for the distribution of ras sequences. The polynucleosomal fraction was further resolved by sucrose gradient sedimentation. Southern-blot hybridization of the DNA isolated from various fractions yielded following results: (1) c-Ha-ras sequences segregated predominantly in the lysate fraction. (2) Unlike the B-globin (transcriptionally inactive) sequences, ras-H associated chromatin lacked typical nucleosomal packaging. Furthermore, since post-translational modifications of nuclear proteins have been suggested to modulate the nucleosome structure during DNA transcription and replication, ras sequences, in polynucleosomes immunofractionated on anti-poly (ADP-Ribose) Sepharose were also examined. The data suggested that the major class of this oncogene sequence exists in chromatin more distal to the sites of this particular chromatin modification.

Base Sequence↗

PubMed1985

Response of mouse tumor to interferon inducer and radiation.

The antitumor effect of interferon inducer poly(ICLC), given prior to the radiation treatment of Lewis lung carcinoma in C57Bl mice was studied. To induce the tumors, the mice were injected subcutaneously into the hind leg with 3 X 10(4) or 3 X 10(5) tumor cells. The combination treatment consisted of poly(ICLC) given at 1.25 mg/kg 6 hours before 400 cGy of 60Co gamma rays. All treatments were given three times over 1.5 weeks. The local response, as measured by the delay in the tumor growth, was significantly higher in the combination treatment group than in poly(ICLC) or local irradiation groups. Following the termination of treatment, tumor regrowth was observed. The survival of poly(ICLC) treated mice was influenced by the number of transplanted tumor cells. Thus, untreated mice which received 3 X 10(4) or 3 X 10(5) (2 or 20 TD50) of tumor cells had similar mean survival time of 25.4 +/- 1.9 and 22 +/- 84 days, respectively (p greater than 0.05). The mice, treated by a combination of poly(ICLC) and local irradiation survived 48.2 +/- 2.1 days and 30.7 +/- 1.2 days (p less than .01), with higher survival in 2 TD50 tumor cell groups. Thus, data obtained in this study in mice showed that administration of an interferon inducer poly(ICLC) prior to local irradiation can improve tumor response and survival.

Animals↗

PubMed1985

[Calcifications after tylectomy and irradiation for breast cancer. Their symptomatic picture and diagnostic value].

In several institutions lumpectomy combined with radiation treatment is being investigated as an alternative method in the primary management of breast cancer (1-5). In 8 of 53 patients, who had undergone this treatment, new calcifications developed after therapy. In 2 of the 53 patients postoperatively persisting calcifications were encountered. The authors report about their preliminary experience in the diagnosis of calcifications after this therapy.

Brachytherapy↗

PubMed1985

Presentation and management of parasellar and suprasellar metastatic mass lesions.

Ten patients with parasellar metastatic lesions presented with insidious painful or painless ophthalmoplegia. Visual loss secondary to a chiasmal syndrome was identified in three of them. A mass lesion was demonstrated by CT scan with precise outlining of the location and size of the lesion. Symptomatic relief was achieved with local radiotherapy in those patients who had early diagnosis.

Adult↗

PubMed1985

Local-regional failure in patients treated with adjuvant chemotherapy for breast cancer.

Risk factors for local-regional recurrence of breast cancer were analyzed in a retrospective review of 117 patients treated with adjuvant CMF (Cytoxan [Mead Johnson & Co, Evansville, Ind], methotrexate, 5-fluorouracil) after radical or modified radical mastectomy at the Vincent T. Lombardi Comprehensive Cancer Center (Washington, DC). The median follow-up time was 50 months after mastectomy. The median time to recurrence was 23 months. The actuarial local-regional failure rate was 19% at five years. Risk of local failure correlated with size of primary (27% for T3 v 15% for T1) and axillary node status (36% for four or more positive nodes v 9% for three or fewer positive nodes). These findings suggest a rationale for the addition of postoperative radiation therapy in high-risk patients treated with adjuvant chemotherapy.

Actuarial Analysis↗