The endoplasmic reticulum-sarcoplasmic reticulum connection: distribution of endoplasmic reticulum markers in the sarcoplasmic reticulum of skeletal muscle fibers.

The skeletal muscle sarcoplasmic reticulum (SR) was investigated for the presence of well-known endoplasmic reticulum (ER) markers: the lumenal protein BiP and a group of membrane proteins recognized by an antibody raised against ER membrane vesicles. Western blots of SR fractions revealed the presence of BiP in fast- and slow-twitch muscles of the rabbit as well as in rat and chicken muscles. Analyses of purified SR subfractions, together with cryosection immunofluorescence and immunogold labeling, revealed BiP evenly distributed within the longitudinal SR and the terminal cisternae. Within the terminal cisternae BiP appeared not to be mixed with calsequestrin but to be distributed around the aggregates of the latter Ca2+ binding protein. Of the various membrane markers only calnexin (91 kDa) was found to be distributed within both SR subfractions, whereas the other markers (apparent molecular masses of 64 kDa and 58 kDa and a doublet around 28 kDa) were concentrated in the terminal cisternae. These results suggest that the SR is a specialized ER subcompartment in which general markers, such as the ones we have investigated, coexist with the major SR proteins specifically responsible for Ca2+ uptake, storage, and release. The differential distribution of the ER markers reveals new aspects of the SR molecular structure that might be of importance for the functioning of the endomembrane system.     

Treatment planning for permanent and temporary percutaneous implants with custom made templates

Nine patients who were presented at MSKCC with primary or recurrent pelvic or head and neck tumors and for whom surgery or further external radiation were excluded, were treated with percutaneous permanent or temporary implants, with individual pre-treatment planning and custom made templates. The tumor dose distributions achieved were as good as for implants performed at the time of surgical exploration. No serious complications have been encountered.     

A pilot study of adjuvant therapy in patients with cervical cancer at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy

The prognosis after surgical therapy (radical hysterectomy and pelvic lymphadenectomy) of stages IB and IIA carcinoma of the cervix is affected by several histopathologic findings within the resected specimen. Patients at high risk of recurrence include those with involved pelvic lymph nodes, lymphatic or vascular invasion in the cervix, tumor size greater than 4 cm, grade 3 lesions, adenosquamous histology, parametrial invasion, and evidence of locally metastatic (noncontiguous) disease. We report the results of adjuvant chemotherapy (cisplatin and bleomycin) and pelvic radiotherapy in 32 patients with cervix cancer deemed to be at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy. The continuous disease-free survival rate for the 32 evaluable patients in 84% at a mean and median follow-up time of 28 months. Three patients are dead of disease and two patients are alive after treatment of local recurrences giving a survival rate of 91%. The two patients who are alive after disease recurrence demonstrated only locally recurrent disease while the three patients who have died with recurrent disease relapsed both locally and systemically. Complications of this treatment program were not significantly greater than those observed in prior studies using the combination of surgery and adjuvant radiotherapy without chemotherapy. When compared with the results from historical controls in a large series of similar patients at the same institution, the results in this pilot study are encouraging and would seem to justify a randomized prospective clinical trial.     

Radiobiological studies of pi-meson at TRIUMF using mouse L5178Y cells

Radiobiological parameters, cell killing, induction of mutations resistant to 6-thioguanine and to methotrexate, and DNA scissions were investigated at the plateau region and peak region of the pion beams of TRIUMF under a preclinical beam condition. The relative biological effectiveness (RBE) of four parameters at the plateau region were nearly 1 using gamma-rays or X rays as the standard radiations. RBE values at the peak regions were varied from one biological parameter to the other. The RBE of cell killing was dependent upon radiation dose; an RBE of 1.9 decreased gradually to 1.2 with an increased radiation dose. The RBE of mutations resistant to 6-thioguanine was dose-dependent and decreased from 1.7 to 1.3 when the dose was increased, while the RBE of mutations resistant to methotrexate was a constant, 1.0. The RBE of DNA scission was a constant 0.7. The radiobiological significance of cell killing and of mutagenesis in pion radiotherapy will be discussed.     

Combined surgery, intraoperative brachytherapy, and postoperative external radiation in stage III non-small cell lung cancer

From March 1977 to December 1980, 318 patients with Stage III non-small cell lung cancer underwent thoracotomy at Memorial Sloan-Kettering Cancer Center. One hundred of these patients, considered for this study, were treated by a multimodality approach consisting of resection and/or intraoperative brachytherapy followed by postoperative external irradiation. The criteria for utilizing intraoperative brachytherapy and postoperative external irradiation were either the presence of residual gross disease (47%) or close resection margins suspected to be involved by the tumor (53%). The intraoperative brachytherapy consisted of a temporary iridium 192 implant for subclinical disease in the mediastinum (median dose, 30 Gy in 3-5 days) and a permanent iodine 125 implant for residual gross disease usually at the primary site (median dose, 160 Gy). All patients received postoperative external beam irradiation consisting of 30 to 40 Gy in 2 to 4 weeks. Seven patients (7%) experienced mild to severe complications after these treatments. The local control, when all gross disease had been removed, was influenced by the presence or absence of tumor at the margins of resection (53% and 89%, respectively). The local control in the patients with gross residual disease treated by brachytherapy and postoperative external irradiation, (40 Gy in 4 weeks) was 72%. The actuarial overall 5-year survival was 22%. The 5-year survival was better in patients who had all gross disease removed as compared with patients who had gross residual disease (30% versus 13%). The disease-free survival in these two groups was 27% and 12%, respectively. This review shows that complete resection and moderate doses of postoperative external irradiation achieves a satisfactory local control and improves survival. When all gross disease cannot be removed, then brachytherapy and postoperative external irradiation may achieve similar local control. Distant metastases still remain a major problem in these patients.