[Breast cancer].

Neoadjuvant chemotherapy (NAC) represents a new approach based on sound theoretical, pharmacokinetic, and experimental principles. The purpose of NAC is to improve control of the primary site by downstaging and to improve control of micrometastatic disease. NAC has been standard therapy in the management of locally advanced breast cancer. Patients with earlier stage breast cancer may also benefit from treatment with NAC. Recently some investigators have mentioned that NAC can be used instead of adjuvant chemotherapy and would be most appropriate for patients who wish to preserve their breast but who have tumors too large for breast conserving surgery. In this article, we reviewed the present status of NAC (indication, clinical response, pathologic response, survival, possibility of breast conservation, prognostic/predictive factors, neoadjuvant endocrine therapy) and discussed several unanswered questions on NAC (survival benefit, optimal number of treatment cycles, optimal regimens) and future direction. Combined modality therapy including NAC appears to provide excellent local control, the possibility of breast conservation, and, probably, an increased survival rate, at least for some subsets of patients. Furthermore, through sequential sampling, NAC provides indeed the opportunity to identify molecular mechanisms associated with pathologic response and to study the possibility to guide the choice for induction treatment and patient populations submitted to neoadjuvant chemotherapy.

Purification and characterization of pyruvate kinase from lamprey (Entosphenus japonicus) muscle.

Pyruvate kinase from skeletal muscle of lamprey (Entosphenus japonicus), which is one of the most primitive living vertebrates, has been purified by approxImately 110-fold. The isolation procedure includes chromatography on Phosphocellulose, Phenyl-5PW, and Sephacryl S-300. Sodium dodecyl sulfate gel electrophoresis shows 59000 as the deduced subunit molecular weight and gel filtration shows 232000 as the tetramer of the subunits. The apparent Km for phosphoenolpyruvate and ADP are 0.41 mM and 0.31 mM at pH 7.4, respectively, when the purified enzyme is saturated with the second substrate. When the enzyme is activated in the presence of fructose-1,6-diphosphate, the Km for PEP changes to 0.087 mM, and the Hill coefficient changes from 1.3 to 0.98.

Skin reactions after breast-conserving therapy and prediction of late complications using physiological functions.

BACKGROUND: The temperature of the skin remains elevated long after breast-conserving treatment with irradiation, perhaps because evaporative cooling is impaired. We investigated physiological changes of the irradiated skin and reevaluated the radiosensitivity of sweat glands on a functional basis to determine whether severe complications can be predicted. METHODS: Breast and axillary skin temperatures were measured with thermography and sweat production in response to local thermal stimuli was measured on the basis of changes in electrical skin resistance with a bridge circuit in 45 women before, during, and after breast irradiation for breast cancer. RESULTS: Breast and axillary skin temperatures were significantly increased after irradiation. In response to cutaneous thermal stimuli, the electric skin resistance of nonirradiated areas decreased significantly because of sweating, but that of irradiated areas was unchanged. CONCLUSION: Impairment of sweating may play an important role in skin damage after irradiation. Although glandular tissue is not usually radiosensitive, the results of our functional assessment suggest that sweat glands are more radiosensitive than expected.

[Factors influencing treatment results of definitive radiotherapy following transurethral surgery for muscle-invasive bladder cancer].

PURPOSE: To determine the prognostic factors influencing the outcome of bladder cancer patients treated with definitive radiotherapy following transurethral tumor resection (TURBT). MATERIALS AND METHODS: From March 1977 through August 1991, 83 patients with muscle-invasive bladder cancer were treated with TURBT (as thoroughly as possible) and definitive radiotherapy (median total dose: 64 Gy, median fractional dose: 2 Gy). Cystectomy was performed when possible for the residual or recurrent invasive cancer following radiotherapy. The median follow-up period was 76 months. RESULTS: The overall survival (OS) and bladder-preserving survival (BPS) rates at 5 years were 38% and 28%, respectively. Univariate analysis indicated that depth of invasion (T2 vs. T3), tumor diameter (< 3 cm vs. > or = 3 cm), and visible (R1) or not visible (R0) residual tumor after TURBT influenced both OS and BPS. In multivariate analysis, absence of visible residual tumor after TURBT was the only significant prognostic factor related to OS (p < 0.001) and BPS (p = 0.002). Five-year OS and BPS were 54% and 43% in T2-3R0 and 14% and 7% in T2-3R1, respectively. CONCLUSIONS: Absence of visible residual tumor after TURBT was significantly associated with better overall survival and bladder-preserving survival for muscle-invasive bladder cancer patients treated with definitive radiotherapy following TURBT.

[Usefulness of visualized highly sensitive new chemical dosimeter: application to blood irradiation].

In the prophylaxis of post-transfusion GVHD, it is recommended to irradiate blood components with an absorbed dose ranging from 15 Gy to 50 Gy. We applied a new chemical dosimeter to measure absorbed dose for blood irradiation. This system is composed of diphenyliodoniumchloride (DICI) as an oxidizer and crystal violet lactone as a pH indicator. Protons are released from DICI after irradiation. The maximum absorption wavelength of this indicator is 610 nm, and absorbance is linearly related with a given dose from 1 to 50 Gy. Coloration is stable for at least 2 weeks when stored in the dark at 4 degrees C. This system may be used as a chemical dosimeter for blood irradiation.

[Therapeutic ratio of fractionated high-dose-rate against continuous low-dose-rate brachytherapy analyzed by simulation model].

In order to establish the standard schedule of 192Ir-HDR brachytherapy, it is necessary to determine the optimal time-dose-fractionation. A new simulation model was used to determine the optimal schedule. This model, which is based on the LQ-model, includes the effect of incomplete repair between fractionations. The fraction surviving after irradiation is expressed as log (surviving fraction) = n (-alpha x -beta x2)-n beta x2 hn (theta), and the change in fractionation will influence the value of hn (theta). From analysis of this model, the therapeutic ratio will approach one if two fractionations (6-hour and 18-hour intervals) or three fractionations (4-hour, 4-hour and 16-hour intervals) in a day are carried out for 6 days. This simulation model will provide an optimal treatment schedule for tumor control, for example, two daily fractionations of 4.6Gy with 6-hour intervals between the daily fractionations (and 18 hours to the first fractionations of the next day), 12 fractionations to 55.2Gy in 6 days or three daily fractionations of 3.3Gy with a 4-hour interval between the daily fractionations (and 16 hours to the first fractionations of the next day), 18 fractionations to 59.4Gy in 6 days. Further clinical study should be carried out to confirm this simulation.

[Accelerated fractionation in malignant gliomas].

Recent radiobiological data have indicated that shortening of the overall treatment time could improve the therapeutic ratio of the radiotherapy on malignant gliomas. Twenty-five inoperable or recurrent malignant gliomas were treated with accelerated fractionation, two sessions per day, 1.5-2 Gy per fraction. This regimen was well tolerated by all the patients and the local response was excellent. To attain the local control, however, other effective modality should be combined.

[Adjuvant chemotherapy for stage I and II non-Hodgkin's lymphoma--a seven-year follow up].

From 1975 to 1983, 51 patients of stage I (30) and II (21) of non-Hodgkin's lymphoma were treated with a combination chemotherapy consisting of vincristine, cyclophosphamide and prednisolone as an adjuvant therapy after radiation or operation. The following results were obtained. 1) Nine patients in stage I and 7 in stage II relapsed, so that 10 year-relapse free survival rates were 68% in stage I and 67% in stage II, respectively. 2) Three patients in nodal lymphomas, 7 in Waldeyer's ring lymphomas and 6 in extranodal lymphomas relapsed, so that 10 year-relapse free survival rates were 80%, 48% and 72%, respectively. 3) Ten year-survival rates were 86% in stage I and 70% in stage II. 4) Ten year-survival rates were 82% in nodal lymphomas, 62% in Waldeyer's ring lymphomas and 86% in extranodal lymphomas. 5) Ten patients relapsed within 1 year, 4 between 1-5 years and 2 after 5 years. Relapses occurred in other than primary sites in most patients. These results suggest that an adjuvant chemotherapy is useful for localized non-Hodgkin's lymphoma, but more intensive chemotherapy before local treatments is necessary.

[Therapeutic gain factor of multiple fractions per day].

Treatment with multiple fractions per day would be expected to offer a significant therapeutic gain. Clinical benefits from the therapeutic gain, however, depend on the steepness of dose-response curves for the tumor control. We discussed the therapeutic gain factor of hyperfractionation and accelerated fractionation in head and neck cancer and malignant glioma, and also discussed the impacts of this factor on the local control of the tumors.

[Radiotherapy for T1 and T2 carcinomas of the tongue: combination therapy using low-dose external irradiation and an interstitial implant].

Between January 1975 and October 1984, 114 previously untreated patients with squamous cell carcinoma of the tongue were treated by a radical course of irradiation at the Jikei University Hospital. Of these patients, eighty with T1 or T2 lesions are analyzed in this paper, some having been treated with an interstitial implant alone or with a combination of external irradiation and an interstitial implant. The two-year local control rate of the primary lesion reached 85% in T1 patients, and 68% for those graded T2. Late radiation injuries were seen in 18% of the cases with local control beyond one year. Most of these injuries, however, healed with conservative therapy. The cumulative 5-year survival rate was 75% in T1 patients, and 52% for those graded T2. The combination of low dose external irradiation (20-30 Gy) and an interstitial implant showed the same local control rate, the same incidence of late injury, and the same survival rate as those who received an interstitial implant alone. In cases that were given combination therapy, the sum dose of about 80 Gy was necessary for local control.

[Radiation tolerance dose of the spinal cord following conventionally fractionated irradiation].

409 patients whose spinal cord were irradiated over 30 Gy with conventionally fractionated method were surveyed to study the relation between the dose of spinal cord and the incidence of radiation myelitis. Radiation myelitis was observed in 26 cases including 3 transverse myelitis ones. 5 year incidences of transverse myelitis calculated with life table method were approximately 0% at 40 Gy, 5% at 50 Gy, 10% at 60 Gy and 20% at 70 Gy. The radiation tolerance dose of the spinal cord was considered to be 50 Gy.

[Results of radiation therapy of nasopharyngeal cancer].

The results of irradiation therapy for nasopharyngeal carcinoma in 49 patients treated at the Department of Radiology, Jikei University of Medicine, between 1968 and 1981 are reviewed. The CR rate increased in proportion to increased dosage, especially in well-differentiated squamous cell carcinoma. The five-year cumulative survival rate was 40% in all stages. Severe late radiation injury occurred in two patients.

Independent effect of a mixed-beam regimen of fast neutrons and gamma rays on a murine fibrosarcoma.

Biological effectiveness of a mixed-beam regimen of fast neutrons and photons was studied in an animal tumor system. NFSa , a spontaneous fibrosarcoma in a C3H mouse, was transplanted in the right hind legs of syngeneic male mice and locally irradiated with a single dose or five daily doses. Tumor control experiments showed that five gamma-ray doses increased TCD50 values by 20 Gy and produced a shallower slope on the dose-response curve compared to that after a single fraction. Fractionated neutron doses also increased the TCD50 value by 9 Gy without changing the slope of the dose-response curve. A mixed-beam regimen of N-gamma-gamma-gamma-N resulted in an independent effect on the tumor. Second, tumor cell survival was examined by the lung colony assay. Nembutal anesthesia reduced the tumor oxic cell fraction, resulting in a single component dose-response curve after a single gamma ray. Five fractionated doses of gamma rays increased both D0 and extrapolation number while those of fast neutrons increased only extrapolation number. The D0 and extrapolation number of the mixed-beam regimen were again identical to those values assuming that the mixed-beam effect was independent. RBEs obtained from cell survival were fairly close to those from TCD50 assays except single-dose experiments.