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Biomedical subjects

E Malaise

Publications and source records attributed to E Malaise.

At least 19 recordsLinked to original sources
PubMed1995

Very accelerated radiation therapy: preliminary results in locally unresectable head and neck carcinomas.

PURPOSE: To report preliminary results of a very accelerated radiation therapy Phase I/II trial in locally advanced head and squamous cell carcinomas (HNSCC). METHODS AND MATERIALS: Between 01/92 and 06/93, 35 patients with an unresectable HNSCC were entered in this study. Thirty-two (91%) had Stage IV, and 3 had Stage III disease. The mean nodal diameter, in patients with clinically involved nodes (83%), was 6.3 cm. The median Karnovsky performance status was 70. The treatment consisted of a twice daily schedule (BID) giving 62 Gy in 20 days. RESULTS: In all cases, confluent mucositis was observed, which started about day 15 and resolved within 6 to 10 weeks. Eighty percent of patients had enteral nutritional support. The nasogastric tube or gastrostomy was maintained in these patients for a mean duration of 51.8 days. Eighteen patients (53%) were hospitalized during the course of treatment due to a poor medical status or because they lived far from the center (mean 25 days). Nineteen patients (56%) (some of whom were initially in-patients) were hospitalized posttreatment for toxicity (mean 13 days). Five patients (15%) were never hospitalized. During the follow-up period, 12 local and/or regional failures were observed. The actuarial 18-month loco-regional control rate was 59% (95% confidence interval, 45-73%). CONCLUSIONS: The dramatic shortening of radiation therapy compared to conventional schedules in our series of very advanced HNSCC resulted in: (a) severe acute mucosal toxicity, which was manageable but required intensive nutritional support in all cases; and (b) high loco-regional response rates, strongly suggesting that the time factor is likely to be critical for tumor control in this type of cancer.

Aged↗
PubMed1991

Blood cell kinetics after a 385 cGy total body irradiation given to a CML patient for bone marrow transplantation.

Fractionated total body irradiation was given to a patient with chronic myeloid leukemia as part of a conditioning regimen for bone marrow transplantation. The radiation treatment was discontinued after the third fraction (total dose: 385 cGy) and no bone marrow graft was given because of the patient's refusal. Peripheral blood lymphocyte levels were monitored for 3 months and lymphocyte subsets up to 50 days post-irradiation. Lymphocyte numbers reached the nadir 48 h after the last fraction and lymphopenia was still present 3 months later. All lymphocyte subsets (T, B, CD4 and CD8 cells) showed a similar decrease except for natural killer cells which exhibited a larger decline. The regenerative capacity of T cells, CD4 subset and natural killer cells was less than that of B cells and CD8 lymphocyte subsets.

Adult↗
PubMed1990

Clinical basis for TBI fractionation.

Most available clinical data strongly suggest a sparing effect of TBI fractionation for the lungs, liver, lens, the growth cartilage and, perhaps the prepubertal ovary; the usual fractionated TBI regimens, delivering from 12 to 15 Gy, appear to be constantly less toxic than the "standard" 10 Gy single dose TBI scheme. However, there is also some clinical suggestion, essentially coming from the T-depleted graft experience, that the largely used 12 Gy fractionated scheme (6 X 2 Gy) might be less effective than the standard 10 Gy single dose TBI for leukemia cell killing and for eradication of the recipient bone marrow. Additional clinical data, ideally coming from well designed randomised trial or from careful large-scale retrospective evaluations, should help to optimize the TBI delivery.

Bone Marrow Transplantation↗
PubMed1989

Growth rate, kinetics of tumor cell proliferation and long-term outcome in human breast cancer.

Thymidine labelling index (LI) was prospectively assayed in vitro in a series of 128 consecutive patients with breast cancer. The follow-up was longer than 15 years for all patients. The distribution of LI was log normal and patients were subdivided into 3 groups (patients with LI = m +/- sigma, lower than m - sigma and greater than m + sigma where m is the geometrical mean). The incidence of relapse and death remained significantly lower in the group with a low LI than in the 2 other groups, whereas the difference between the 2 other groups faded away when follow-up exceeded 10 years. Multivariate analyses show that LI is one of the two most important independent prognostic indicators for relapse or death, the other being histological grading. Data concerning 2,648 patients treated at our Institute, prior to the introduction of chemotherapy into treatment protocols, have been used to investigate the influence of tumor growth rate on the probability of distant dissemination. A model of the natural history was used, in order to generate metastasis appearance curves, in 3 subgroups of patients, according to the value of the tumor doubling time (TDT). Our results show that after a follow-up exceeding 8 years, there is no longer any difference between the subgroups of patients with rapid or intermediate growth rate, whereas after 25 years large and highly significant differences in relapse and survival between the slow-growing tumors and the other two subgroups still remain. These two sets of data concur to show that tumor growth rate or proliferation rate correlates with the probability of metastatic dissemination.

Breast Neoplasms↗
PubMed1989

Single dose versus hyperfractionated total body irradiation before allogeneic bone marrow transplantation: a non-randomized comparative study of 54 patients at the Institut Gustave-Roussy.

At the Institut Gustave-Roussy (IGR), from January 1982 to December 1986, 54 patients received total body irradiation (TBI) as a part of the conditioning regimen before allogeneic bone marrow transplantation. The patients were non-randomly assigned to either single dose TBI (STBI) (31 patients receiving 10 Gy at a 4.5 cGy/min dose rate, 8 Gy to the lungs) or to a hyperfractionated scheme (HTBI) (23 patients receiving 13.2 Gy in 11 fractions, 3 fractions per day, 9 Gy to the lungs). Relapse rate and overall survival were not significantly different in the two STBI and HTBI groups, in spite of a larger number of 2nd and 3rd remission patients in the HTBI subset. The incidence of interstitial pneumonitis (IP) was significantly reduced in the HTBI group (13%, versus 45% after STBI, p = 0.02). Lethality by IP was also lower after HTBI (4%, versus 26% after STBI, p = 0.08). There was no case of veno-occlusive disease of the liver in the HTBI group, whereas three cases were observed after STBI. Based on these results, the IGR activated, in January 1987, a randomized trial comparing the single dose 10 Gy TBI (8 Gy to the lung) to a new hyperfractionated schedule (11 fractions of 1.35 Gy, 3 fractions per day, 9 Gy to the lungs).

Adult↗
PubMed1988

Late toxicity of radiotherapy in Hodgkin's disease. The role of fraction size.

From 1972 to 1976 patients at the Gustave Roussy Institute were irradiated for Hodgkin's disease using a modified fractionation schedule (3 fractions of 3.3 Gy per week) for operational reasons. From 1964 to 1971 and from 1977 to 1981, a more conventional regimen (4 fractions of 2.5 Gy per week) was used. The rates of the late complications in these two subsets of patients treated with different fractionation schedules at the same total dose of 40 Gy during the same overall time were compared. Mediastinitis was observed in 19% of the '4 X 2.5 Gy/week' group versus 56% in the '3 X 3.3 Gy/week' group. Pericarditis in 0% versus 9%, gastroduodenal ulceration and severe gastritis in 10 versus 21% and small bowel obstruction in 5 versus 8%. When using the linear quadratic model with an alpha/beta of 2.5 Gy to evaluate the equivalent dose of 40 Gy given in 12 fractions of 3.3 Gy when delivered by fractions of 2.5 Gy, a value of 46.6 Gy is found. This difference of 6.6 Gy in the equivalent doses (for late toxicity) is likely to account for the significant increase of late radiation injuries, such as mediastinitis and pericarditis, in the present study. The local relapse rate was found to be slightly lower in the 3 X 3.3 Gy group. However, this possible benefit cannot offset the considerable increase of late complications.

Dose-Response Relationship, Radiation↗
PubMed1985

Radical irradiation and misonidazole in the treatment of advanced cervical carcinoma: results of a phase II trial.

Between February 1979 and January 1982, a Phase II study of misonidazole as a radiosensitizer was performed in 34 patients with advanced carcinoma of the uterine cervix. Twenty-nine patients were treated with conventional fractionated radiation and five patients with a twice daily fractionation schedule, 3 days a week. The total dose to the whole pelvis was 5000 cGy delivered in 5.5 weeks. Intracavitary curietherapy delivered an additional boost to the tumor. Misonidazole was given to all patients during external radiation and to 25 patients during intracavitary treatment for a total dose of 11 to 14 g/m2. All patients were followed for at least 28 months after treatment with a median follow-up of 52 months. Misonidazole toxicity included peripheral neuropathy (18%) and central nervous system toxicity (3%). The 3-year survival rate is 74% and the 3-year disease-free survival is 57%. When compared to our historical group survival, 42 and 12% for Stage III and IV, respectively, our data suggest that there is a probable advantage from using misonidazole in advanced carcinoma of the cervix.

Female↗
PubMed1978

Spontaneous transformation of bovine lens epithelial cells: kinetic analysis and differentiation in monolayers and in nude mice.

Bovine lens epithelial cells, in vivo, are known to perform two determined functions. First, they synthesize the lens capsule and subsequently, in the germinal region, they differentiate in fiber cells with massive production of crystallin proteins, inactivation and pyknosis of the nucleus. Bovine lens epithelial cells from adult origin can be cultured but so far no massive crystallin production has been demonstrated in vitro. We have studied the growth and differentiation of these cells and shown that in long term culture they acquire spontaneously many characteristics of transformation: unlimited growth potential, abnormal karyotype, multilayering. Viral particles were scarcely detected. However, they retain their epithelioid character and the ability to synthesize lens capsule material. Kinetic characteristics of those cells have been determined. When injected into nude mice, they actively proliferate and form tumors in which synthesis of alpha-crystallin can be demonstrated. These results show that in vitro transformation of lens epithelial cells does not affect their potential for terminal differentiation.

Animals↗
PubMed1978

Effects of low dose rate irradiation on the division potential of cells in vitro. IV. Embryonic and adult human lung fibroblast-like cells.

Early and late passage human embryonic lung fibroblasts were compared with early passage adult lung fibroblasts with regards to their survival (number of population doublings), after low dose rate ionizing radiation. It was found that early passage embryonic cells are quite resistant to this type of radiation. Late passage embryonic and early passage adult fibroblasts are more sensitive to ionizing radiations. The results suggest that cell aging is accompanied by an increased sensitivity to low dose rate ionizing radiation and favor the idea that aging in vitro, expressed as a function of the fibroblast division potential, is correlated with aging in vivo.

Cell Division↗
PubMed1977

Concept of fibroblast aging in vitro: implications for cell biology.

Aging in vitro is defined as the progressive growth decline of mass populations of fibroblastlike cells leading to their eventual loss after serial subcultivations. Different species are compared in terms of the doubling potential of their fibroblasts in culture. A gradient like behavior is found with at one end species whose fibroblasts invariably die after a certain number of doublings and at the other end species yielding fibroblasts with infinite growth potential. The relationship of this phenomenon with cancer and aging is reviewed and discussed. The response of chicken, mouse and human fibroblasts to slow dose rate ionizing radiation fits with the relative positions of these species on the scale relating the probability of yielding fibroblastic populations with infinite life spans. This difference between fibroblastlike cultures is interpreted in terms of the presence or absence of repair mechanisms or of a repairable substrate. The growth potential of fibroblasts in vitro seems to be related to their susceptibility to viral, chemical and physical oncogenes, and could have important implications for the study of evolution.

Adult↗
PubMed1976

Comparison of cell proliferation kinetics in human and experimental tumors: response to irradiation.

Available data on the parameters of cell kinetics in human solid tumors were reviewed. The mean duration of the cell cycle is 2 days; for G1 it is 1 day, for S it is 18 hours, and for G2 it is 6 hours. G1 has the greatest variability from tumor to tumor. The cell cycle and its phases are shorter in animal tumors but the relative durations and variabilities are similar. The labeling index (LI) and the growth fraction vary widely among human tumors, but they are correlated with the histologic type of the tumor. There is a correlation between the mean doubling time and the mean LI of the various histologic types of tumors. Cell loss is considerable in all human tumors, but it is more important in tumors with a high LI. Metastases and recurrence appear to have shorter doubling and cell cycle times than the primary tumor. There seems to be in patients with metastases a correlation between the survival and the growth rate of the metastases. There does not seem to be any correlation between the LI and the probability of dissemination. The depression of LI after irradiation is more important in human tumors than in experimental tumors and varies widely among human tumors. After irradiation, the depopulation seems more important in tumors with a high LI. The histologic groups of tumors with a high mean LI are on the average more radiosensitive and more sensitive to drugs.

Animals↗
PubMed1975

Kinetics of tumor growth and of cell proliferation in U.R.D.T. cancers: therapeutic implications.

After a brief survey of the factors of clinical tumor radioresistance the available data on the growth rate and on the kinetics of cell proliferation of U.R.D.T. tumors are reviewed. The growth fraction and the cell turnover rate appear to be similar in U.R.D.T. tumors and in other squamous cell carcinomas. These two parameters are correlated with clinical tumor radiosensitivity and chemosensitivity. The possible value of tailoring fractionation and drug administration to the biological characteristics of the tumor is discussed.

Animals↗