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Biomedical subjects

G Rosen

Publications and source records attributed to G Rosen.

At least 145 records · Page 8Linked to original sources
PubMed1985

Preoperative (neoadjuvant) chemotherapy for osteogenic sarcoma: a ten year experience.

During the past ten years, (November 1973 through November 1983) 208 patients with fully malignant primary osteogenic sarcoma of an extremity were treated with preoperative chemotherapy on four successive treatment protocols. Continuous improvements in the disease-free survival of patients were attributed to refinements in the chemotherapy regimens. These refinements were made after direct observation of the response of the primary tumor to chemotherapy. At a minimum follow-up time of 36 months for 87 patients treated on the T-10 chemotherapy protocol, 67 (77%) have remained alive and continuously free of disease, and 71/87 (81.6%) are currently free of disease. Of the entire group of 208 patients receiving preoperative chemotherapy, 150 (72%) have remained continuously free of disease, and 158/208 (76%) are currently free of disease from three to 11 years (median five years). The overall complete response rate of the primary tumor to preoperative chemotherapy was 49%. Relapses in 19 patients with tumors about the knee were attributed to local recurrences following en bloc resection. Of the 58 patients undergoing amputation following preoperative chemotherapy, 46/58 (79.3%) have remained alive and continuously free of disease. 23/25 patients (92%) having undergone resection for proximal humerus lesions remain alive and free of disease at this time. There have been no local recurrences for patients having humeral resections. Preoperative chemotherapy has given rise to better chemotherapy regimens, higher cure rates, and the appropriate selection of the best postoperative therapy for patients with osteogenic sarcoma.

Adult↗
PubMed1985

Neoadjuvant chemotherapy for osteogenic sarcoma: a five year follow-up (T-10) and preliminary report of new studies (T-12).

During the past 10 years, (November, 1973 through November, 1983) 208 patients with fully malignant primary osteogenic sarcoma of an extremity were treated with preoperative chemotherapy on 4 successive treatment protocols. Continuous improvements in the disease-free survival of patients were attributed to refinements in the chemotherapy regimens. These refinements were made after direct observation of the response of the primary tumor to chemotherapy. At a minimum follow-up time of over 38 months for 87 patients treated on the T-10 chemotherapy protocol, 67 (77%) have remained alive and continuously free of disease, and 71/87 (81.6%) are currently free of disease at a median follow-up time of 5 years. Overall complete response rate of the primary tumor to preoperative chemotherapy was 48%. Fifty-one patients were treated on a pilot protocol (T-12) from November, 1981, to November, 1983. The main difference was that after preoperative high dose methotrexate and combination bleomycin, cytoxan and dactinomycin therapy, patients having a good histologic response of the primary tumor (21/51 or 41%) had their chemotherapy stopped at 15 weeks and did not receive platinum or Adriamycin chemotherapy. 38/51 (75%) on T-12 remained continuously free of disease and 39/51 (76%) are currently alive and free of disease. There were 2 local recurrences on the T-10 protocol and 6 on the T-12 protocol. Excluding local recurrences 71/85 (84%), patients treated on T-10 are currently alive and free of disease and 38/45 (84%) patients treated on T-12 are alive and free of disease (at a median follow-up of 24 months for T-12). This preliminary study indicates that preoperative chemotherapy may be used to select a subset of patients (who respond well to preoperative high dose methotrexate) who can have therapy terminated early, sparing those patients the undesirable side effects and cost of additional therapy with platinum and Adriamycin.

Adult↗
PubMed1984

Detection by high-performance liquid chromatography of methotrexate and its metabolites in tumor tissue from osteosarcoma patients treated with high-dose methotrexate/leucovorin rescue.

Methotrexate (MTX) polyglutamates were detected in osteogenic sarcoma tumor samples obtained from patients 24 or 48 h after receiving high-dose MTX/leucovorin rescue therapy. Tumor samples were assayed by high-performance liquid chromatography, and polyglutamyl metabolites, along with MTX, were quantitated using both direct u.v. absorption at 313 nm and an enzyme titration assay. Good agreement between these two methods was found although the more sensitive enzyme assay detected peaks in some samples not detected by u.v. absorbance. A wide variation in MTX:MTX polyglutamate levels (1:1 to 25:1) was found among the six clinical samples studied. Also, no correlation between the extent of polyglutamate formation and plasma levels (determined at the time of tumor sampling) was observed. High intracellular levels of a derivative which appears to be the 7-hydroxy metabolite of MTX were also detected in four of six samples. This material coeluted with authentic standard, showed spectral properties like standard 7-OH-MTX, and did not inhibit dihydrofolate reductase.

Chromatography, High Pressure Liquid↗
PubMed1984

Semiquantitative gallium scintigraphy in patients with osteogenic sarcoma.

Sequential gallium scans were performed in 37 patients with newly diagnosed osteogenic sarcoma. High gallium uptake was found more often in males in the 10 to 19 age group and in femoral lesions. High uptake was also seen in patients who had predominantly osteoblastic or mixed changes on radiographs and in those who had a soft tissue mass. Following chemotherapy, significant decrease of tumor to nontumor ratio occurred in the patients who responded to treatment as shown by a Grade III or IV response on histologic examinations at the time of en bloc resection. It is concluded that semiquantitative gallium scintigraphy is useful in monitoring therapeutic response in patients with osteogenic sarcoma.

Adolescent↗
PubMed1984

Primary osteogenic sarcoma of the femur: a model for the use of preoperative chemotherapy in high risk malignant tumors.

The value of adjuvant chemotherapy in primary osteogenic sarcoma (OSA) is still considered controversial by some. One reason may be that various reported series include patients with widely varying prognostic variables. To address this, the effect of chemotherapy on the continuous disease-free (CNED) survival was analyzed in 100 patients aged 21 yr or less with OSA of the femur. This classically poor prognostic group of patients represented 51% of all primary OSA seen at the Memorial Sloan-Kettering Cancer Center during the study interval. This study includes all patients aged 21 yr or less with fully malignant (Grade III-IV/IV) OSA of the femur and no metastases treated from November 1973 through November 1981. The first (T-4) protocol (31 patients) consisted of high dose methotrexate (HDMTX) with leucovorin rescue, cyclophosphamide (Cyc), and adriamycin. In the second (T-7) protocol (23 patients) the dose of HDMTX was increased to 12 g/m2 for prepubescent patients, and bleomycin, Cyc, and dactinomycin replaced Cyc. The current (T-10) protocol (46 patients) uses the same CT as T-7, but patients not having a complete response of the primary tumor to preoperative CT receive additional cisplatinum (120 mg/m2) with adriamycin (30 mg/m2/day for two consecutive days). In 31 patients treated with T-4 the CNED survival was 32% with a minimum follow up of over 7 yr. On T-7, 15/23 patients with femur primaries had a CNED survival of 65% with all of the surviving patients followed for more than 5 yr. The addition of cisplatinum in T-10 has resulted in CNED survival rate of 77% in 34/44 patients (excluding two patients that died CNED during and after treatment); the median follow-up patients who are alive CNED is 33 months, with a minimum of 2 yr follow up on the last patient entered.

Adolescent↗
PubMed1984

An anterior surgical approach to the upper thoracic vertebrae.

Of the various anterior surgical approaches to the spine, exposure of the upper two thoracic vertebrae remains the most challenging. An operative approach to this region is described. The major features include resection of a portion of the clavicle and the manubrium sterni. Following resection of the tumor and involved vertebra, anterior fusion is performed using the clavicle as a strut graft. Immediate stabilization may also be achieved with methyl methacrylate replacement of the vertebral bodies. The operation is well tolerated, and requires minimal postoperative immobilization. The clinical presentation, radiological features, and results of treatment in a series of seven patients operated on during a 2-year period are presented.

Abscess↗
PubMed1983

Properties of ATP tightly bound to catalytic sites of chloroplast ATP synthase.

Under steady state photophosphorylating conditions, each ATP synthase complex from spinach thylakoids contains, at a catalytic site, about one tightly bound ATP molecule that is rapidly labeled from medium 32Pi. The level of this bound [32P]ATP is markedly reduced upon de-energization of the spinach thylakoids. The reduction is biphasic, a rapid phase in which the [32P] ATP/synthase complex drops about 2-fold within 10 s, followed by a slow phase, kobs = 0.01/min. A decrease in the concentration of medium 32Pi to well below its apparent Km for photophosphorylation is required to decrease the amount of tightly bound ATP/synthase found just after de-energization and before the rapid phase of bound ATP disappearance. The [32P]ATP that remains bound after the rapid phase appears to be mostly at a catalytic site as demonstrated by a continued exchange of the oxygens of the bound ATP with water oxygens. This bound [32P]ATP does not exchange with medium Pi and is not removed by the presence of unlabeled ATP. The levels of tightly bound ADP and ATP arising from medium ADP were measured by a novel method based on use of [beta-32P]ADP. After photophosphorylation and within minutes after the rapid phase of bound ATP loss, the measured ratio of bound ADP to ATP was about 1.4 and the sum of bound ADP plus ATP was about 1/synthase. This ratio is smaller than that found about 1 h after de-energization. Hence, while ATP bound at catalytic sites disappears, bound ADP appears. The results suggest that during and after de-energization the bound ATP disappears from the catalytic site by hydrolysis to bound ADP and Pi with subsequent preferential release of Pi. These and related observations can be accommodated by the binding change mechanism for ATP synthase with participation of alternating catalytic sites and are consistent with a deactivated state arising from occupancy of one catalytic site on the synthase complex by an inhibitory ADP without presence of Pi.

ATP Synthetase Complexes↗
PubMed1983

Mesenchymal chondrosarcoma. A clinicopathologic analysis of 35 patients with emphasis on treatment.

Almost a quarter of a century has passed since mesenchymal chondrosarcoma, a rare, insufficiently studied and still poorly understood cartilage neoplasm has been described. Based on 35 cases diagnosed and treated at this Cancer Center, this study found 20 males and 15 females with an average age of 26 years (range, 6-70 years). All but five of the tumors arose in the skeleton in the femur, humerus, and ilium in five cases each, while the os calcis (a rare site for any other osseous tumor) gave rise to this tumor in four instances. Pain was the cardinal symptom in 27 patients. The lesional size varied from 4 to 18 cm (average, 9.5 cm). Histologic examination revealed nine of the tumors to be of the small cell undifferentiated types while the others were of the "hemangiopericytomatoid" variant. According to this subclassification, patients with the small cell type of lesions responded to combination chemotherapy and irradiation, as usually do other small cell sarcomas. The addition of surgical resection may be of value especially in the patients with the hemangiopericytomatoid variant. Preliminary results in the treatment of five such patients with evaluable disease suggest that this combined treatment approach is encouraging. Follow-up analysis of all patients revealed a 37.9 months median survival, and 28% to be alive at ten years.

Adolescent↗
PubMed1983

Chemotherapy of malignant fibrous histiocytoma of bone. A report of five cases.

Five patients with evaluable malignant fibrous histiocytoma (MFH) of bone (three with primary tumor and two with primary tumor and metastatic disease) were treated with preoperative chemotherapy including high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) as is used for patients with osteogenic sarcoma. All five patients demonstrated a clinical response to chemotherapy. Three of four patients who underwent surgery had complete responses and one patient had greater than 90% tumor necrosis as documented by histologic examination of the resected primary tumor. All four patients who underwent surgery following preoperative chemotherapy are surviving free of disease from one to six years from the start of treatment; chemotherapy was discontinued after six to 11 months in these patients. The median disease-free survival time is 31.5 months. This study demonstrates the effectiveness of chemotherapy in MFH of bone, and in particular the effectiveness of HDMTX with CFR which caused measurable responses in all patients while receiving this therapy as a single agent.

Adolescent↗
PubMed1983

Sepharose-stearate as substrate for rat liver long-chain fatty acyl-CoA synthetase.

Stearic acid coupled covalently to Sepharose 6B serves as substrate for thioesterification catalyzed by rat liver long-chain fatty acyl-CoA synthetase (ATP-forming) (EC 6.2.1.3). Availability as substrate is dependent upon the conservation of the free omega-terminal in addition to that of the free carboxyl function. The enzymatic overall formation of matrix-acyl-CoA in the presence of ATP and CoA as cosubstrates conforms to the stoichiometry reported for thioesterification of the free long-chain fatty acyl substrate. The preformed matrix-acyl-CoA serves as substrate for the backward synthetase reaction in the presence of AMP and PPi. The apparent Km values for ATP and CoA in the presence of the acyl matrix are similar to the respective Km values observed in the presence of the free acid substrate. The apparent Km for the acyl matrix is 10-fold higher (0.5 mM) than the apparent Km value for the free acid. The feasibility of enzymatic thioesterification of bound long-chain fatty acids implies that the exact nature of the bulky chain situated between the carboxy and omega-terminal plays a secondary role in defining the fatty acyl substrate specificity for long-chain fatty acyl-CoA synthetase. Also, dissociation of bound long-chain fatty acids does not constitute an obligatory preliminary step to fatty acid thioesterification.

Animals↗
PubMed1983

Chemical pleuritis as the cause of acute chest pain following high-dose methotrexate treatment.

This report describes the clinical and roentgenographic features of a pleuritis seen following the administration of high-dose methotrexate (HDMTX). Among 210 patients who received 3130 courses of HDMTX from 1977 through 1980, the incidence of this clinical entity was 8.5% (n = 18). The sudden onset of chest pain occurred only after the third or fourth HDMTX treatment and usually lasted between three and five days; the pain was often quite severe and led to extensive clinical examination before recognition of the benign transient nature of this syndrome. Roentgenographic examination of the chest revealed thickening of the intralobar pleura, most prominent on the right side. Our observations support the hypothesis that this adverse drug reaction occurs more frequently than assumed, but is often ignored or misinterpreted.

Adolescent↗
PubMed1983

The inability of oral leucovorin to elevate CSF 5-methyl-tetrahydrofolate following high dose intravenous methotrexate therapy.

Osteosarcoma patients free of CNS metastases are at risk for acquiring leukoencephalopathy after receiving multiple courses of high dose intravenous methotrexate followed by oral leucovorin rescue (MTX-LV). A prospective study of the adequacy of CNS rescue of MTX biochemical toxicity by oral leucovorin was undertaken in newly diagnosed neurologically normal osteosarcoma patients. Prior to surgical resection of the primary tumor, ten patients received 4 weekly courses of MTX-LV. During the fourth weekly MTX-LV treatment, 0 and 72 hr serum and CSF determinations of MTX, 5-methyl-tetrahydrofolate (5-MTHF) and LV were made. No CSF MTX was detectable at 0 hr in any patient, but a significant elevation in CSF MTX occurred in 9/9 patients at 72 hr (mean 47.2 +/- 31.8 ng/ml or 1.04 +/- 0.7 X 10(-7) M). There was no significant change in mean CSF 5-MTHF over 72 hr despite a rise in serum 5-MTHF. MTX exceeded 5-MTHF in 6/9 patients in CSF, whereas only 3/8 patients had higher MTX in the serum at 72 hr. No acute systemic or neurotoxicity was seen. The failure of oral leucovorin to consistently elevate CSF 5-MTHF levels at 72 hr in the context of significant levels of CSF MTX may result in intermittent CNS folate deficiency. The clinical and pathological syndrome of leukoencephalopathy may be related to this phenomenon and may evolve after repeated MTX-LV treatments.

Adolescent↗
PubMed1983

Primary osteogenic sarcoma: eight-year experience with adjuvant chemotherapy.

Since October 1973, 185 patients 21 years of age or younger with primary osteogenic sarcoma of an extremity were treated with adjuvant chemotherapy. Twenty-five of the first fifty-two patients (48%) have remained free of disease for a median of 7 years. In the next chemotherapy protocol most patients had chemotherapy prior to amputation or resection, during which time the dose of high-dose methotrexate was escalated in many patients to that needed to shrink the primary tumor. For a median of 4 years 43 of 54 patients (80%) have remained free of disease. In the current protocol, the response of the primary tumor to chemotherapy with high-dose methotrexate was used to select postoperative adjuvant chemotherapy for the patient. With the latter approach 73 of 79 patients (92%) have remained continuously free of disease for a median of 2 years. This experience demonstrates the value of chemotherapy in increasing the cure rate in osteogenic sarcoma and that the response to preoperative chemotherapy can help select postoperative chemotherapy to produce an even higher potential cure rate for osteogenic sarcoma.

Adolescent↗
PubMed1983

Otitis media with effusion--complications after treatment.

In this work we have followed 64 patients suffering from OME (otitis media with effusion) who had ventilating tubes (VT) introduced between 1967 and 1971. In 82 ears (78.8 per cent of cases) recovery and improvement were observed. In one of the ears, a long-standing perforation was noted. In 11 cases (10.5 per cent), after more than 10 years, further treatment and follow-up were mandatory; these patients suffered from some attic disease. In eight cases the attic retraction was under control; in three other cases the disease progressed in spite of treatment, and they underwent surgery.

Child↗