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Biomedical subjects

J Estrada

Publications and source records attributed to J Estrada.

16 recordsLinked to original sources

t(12;17)(p13;q21) in early pre-B acute lymphoid leukemia.

Structural rearrangements involving the short arm of chromosome 12 occur in 10% of cases of childhood acute lymphoid leukemia. The translocation t(12;17)(p13;q21), an uncommon 12p abnormality, was identified in five of 2620 cases (0.2%) successfully karyotyped by the Pediatric Oncology Group or St Jude Children's Research Hospital. All five cases were classified as early pre-B; however, CD10 (common acute lymphoblastic leukemia antigen) was expressed at lower levels than other markers of B-cell lineage. Two cases also expressed the myeloid-associated antigen CD33. Leukemic cells were pseudodiploid in four cases, with an extra chromosome 21 in the fifth case. All of these patients achieved complete remission. Two relapsed during subsequent therapy, and three remain in continuous remission for greater than or equal to 20 months.

Adolescent

Phase II trial of mitoxantrone in acute lymphocytic leukemia of childhood. A Pediatric Oncology Group study.

Thirty children with refractory acute lymphocytic leukemia (ALL) were treated with mitoxantrone, 8 mg/m2/day, for 5 days. Three children received a second course of the drug 3 to 4 weeks later. All but two patients had received prior anthracycline therapy. There were 2 complete responses, 4 early deaths, and 24 patients with persistent leukemia. Of the 21 patients with circulating blasts at the start of mitoxantrone who did not achieve remission, 16 (76%) had complete clearance of their peripheral blood blasts. Although all patients developed profound neutropenia (less than 100 per mm-3), mucosal and hepatic toxicities were uncommon and mild. Mitoxantrone has moderate activity in childhood ALL and should be considered for further trials in less heavily pretreated patients.

Adolescent

Anterior pituitary function in Cushing's syndrome: study of 36 patients.

We studied the anterior pituitary function in 36 patients (25 females and 11 males, mean age: 35 years) with untreated Cushing's syndrome by simultaneous triple stimulus with insulin, TRH and LHRH. Thirty-one patients (86%) had Cushing's disease and five (14%) had an adrenal adenoma. We observed a lack of response of GH to hypoglycemia in 88%, TSH to TRH in 91%, LH to LHRH in 30%, FSH to LHRH in 12% and PRL to TRH in 6% of the patients. Low-to-normal total thyroxine (T4) values were obtained in 37%, with low triiodothyronine levels in 87%. The free-T4 index was normal in all patients. Total testosterone was low in only one adult man, while estradiol and progesterone were low in 45% and 15% of premenopausal women, respectively. We observed no differences in either axis among patients with Cushing's syndrome of different etiologies. Nor was there any statistical difference between the frequency of alteration of each axis and the levels of urinary free cortisol or the duration of the disease. We conclude that hypercortisolism is responsible for the abnormalities in anterior pituitary function in Cushing's syndrome.

Adenoma

Results of external pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease.

Fourteen adult patients (10 females and 4 males; age range 20-60 years) with persistent Cushing's disease after transsphenoidal microsurgery were treated with pituitary irradiation. Supervoltage multiportal administration was employed at a total dose of 50 Gy (+/- 0.65 SD). The interval between microsurgery and pituitary irradiation was less than 6 months in 6 patients and more than 6 months in 8. The pituitary-adrenal axis was evaluated postsurgically, before irradiation and every 6 months thereafter. The remaining anterior pituitary function was simultaneously tested. Remission rates at 12 months and 24 months after radiotherapy were 61 and 70%, respectively. Two patients developed TSH deficiency and another gonadotropin deficiency during the follow-up after radiation. We conclude that pituitary irradiation is the treatment of choice for persistent Cushing's disease after unsuccessful surgery because of its high efficiency and low incidence of adverse reactions when compared with other forms of treatment.

Adrenocorticotropic Hormone

Pediatric osteosarcoma. Successful retreatment of relapsed primary tumor and soft tissue recurrence with intraarterial cis-diamminedichloroplatin-II.

Six patients with extremity osteosarcoma initially underwent successful treatment of the primary tumor with four to seven courses of intraarterial cis-diamminedichloroplatin-II (IA-CDP; 100 to 150 mg/m2/course). The primary tumors in two patients were then extirpated by limb salvage. However, a local soft tissue recurrence occurred in both patients several months later. The other four patients refused surgical intervention and later also developed local bony recurrences. Reinstatement of three to five courses of IA-CDP in all six patients induced a complete response in five. The local recurrences (bony and soft tissue) in all six patients were excised. This included limb-salvage procedures in three patients. Additional postoperative chemotherapy was administered. Four patients remain alive and continuously free of disease 3.5+ to 4.5+ years after retreatment with IA-CDP.

Antineoplastic Combined Chemotherapy Protocols

Musculoskeletal neoplasms after intraarterial chemotherapy: correlation of MR images with pathologic specimens.

The most accurate prognostic indicator in patients with musculoskeletal sarcomas is the percentage of tumor necrosis after intraarterial chemotherapy. Magnetic resonance (MR) imaging was evaluated to determine its ability to indicate the percentage of necrosis in musculoskeletal neoplasms after treatment. Fourteen patients with musculoskeletal neoplasms underwent treatment protocols including intraarterial chemotherapy (n = 14), radiation therapy (n = 6), and systemic chemotherapy (n = 14). All patients underwent MR imaging before and after treatment, and all underwent either limb salvage surgery (n = 8) or amputation (n = 6) within 1 week of the last MR examination. Standard unehanced spin-echo T1-, spin-density-, and T2-weighted MR sequences were used. The MR images were compared with the pathologic specimens. On T2-weighted images, the signal intensities of viable tumor, tumor necrosis, edema, hemorrhage, and necrosis overlapped. With the unenhanced spin-echo technique, MR imaging cannot be used to predict the percentage of tumor necrosis in musculoskeletal neoplasms after intraarterial chemotherapy.

Antineoplastic Agents

[Thyrotropin-producing adenoma of the hypophysis].

A patient with a thyrotropin (TSH) secreting pituitary adenoma had hyperthyroidism with high levels of thyroid hormones and inadequate TSH secretion. After the challenge with thyrotropin releasing hormone (TRH), TSH level did not change. The normalization of plasma levels of thyroid hormones with antithyroid drugs was followed by an important increase in TSH levels. The adenoma was resected by the transphenoidal route and the diagnosis was confirmed by immunohistochemical study. Inadequate TSH secretion persisted after surgery, and radiation therapy with lineal accelerator was attempted. At present, one year after radiation therapy, inadequate TSH secretion requiring antithyroid drugs persists. We describe this clinical picture and briefly discuss the literature.

Adenoma

Experimental model for locally recurring mammary tumors. Development, morphology, karyotype, growth kinetics, and experimental metastatic potential.

A rat model was established for evaluating the biology of locally recurring mammary tumors after surgical resection of the primary tumor. Eight distinct cell lines were independently derived from primary tumors and local recurrences after surgical removal of 13762NF rat mammary adenocarcinoma clone MTF7(T20). In vivo tumor doubling times between the "parental" MTF7(T20) cell line, primary tumor-derived cell lines sc1 and sc3, and the local recurrence (LR) sublines varied after the inoculation of 10(6) tumor cells into the mammary fat pad of female Fischer 344 rats. Doubling times were shorter for LR3, and LR4, LR5, and LR6 than their primaries sc3 and MTF7(T20), respectively, and longer for LR1 and LR1a than their primary tumor sc1. The LR sublines varied considerably for their experimental metastatic potentials. Both increases and decreases in metastatic potential were seen compared to MTF7(T20), sc1, and sc3. Karyotype analysis by G-banding revealed the presence in the LR sublines of several marker chromosomes, previously identified in MTF7 at tissue cultures 11 and 35. Two new chromosome markers were identified: M54, shared by MTF7(T20), sc1, LR4, LR5 and LR6, and M55, shared by MTF7(T20), sc1, LR1, sc3, LR3, LR4, and LR6. These data indicate that local tumor regrowth after surgical excision of the primary tumor in this model most likely selects the growth of tumor cell subpopulations already present within the primary tumor. Differences in growth kinetics, karyotype, and metastatic potential between the parental MTF7(T20), primary tumors sc1 and sc3, and their LR sublines may reflect in vivo influences on the phenotypic diversity generated during the development of local mammary tumor recurrences after surgical treatment of the primary tumor.

Adenocarcinoma

Development and characterization of a rat model for locally recurring mammary tumors: sensitivities to 5-fluoro-2'-deoxyuridine, adriamycin, and X-irradiation.

Local recurrence occurs in 4-47% of breast cancer patients and is often associated with development of metastatic foci and resistant cell populations. Thus, recurrent breast cancer indicates a poor prognosis for the patient. Local tumor-derived 13762NF rat mammary adenocarcinoma cell clone MTF7(T20) was injected into the inguinal mammary fat pad and allowed to grow before surgical excision. Individual locally growing (primary) tumors were removed and established in short-term tissue culture. Corresponding local recurrences were excised after regrowth and established in short-term tissue culture. All sublines were tested for in vitro sensitivities to 5-fluoro-2'-deoxyuridine, Adriamycin, and ionizing X-irradiation. Using a clonogenic colony formation assay, responses of individual sublines ranged from 85 to 1500 ng/ml for Adriamycin and 65 to 10,000 nM for FdUrd. Some recurrences were significantly more resistant while others were more sensitive than the corresponding primary tumor lines. All recurrences had smaller 90% lethal dose values than the corresponding parent or primary tumor in response to Adriamycin; whereas, to 5-fluoro-2'-deoxyuridine, 90% lethal dose values revealed that most lines were quite resistant. Statistically significant differences in radiation survival were observed only for lines LR1a and LR5 (more sensitive). There was no apparent correlation between sensitivities to chemotherapy agents or X-irradiation and experimental metastatic potential in LR sublines. These dose-response data indicate that locally recurrent tumors are frequently, but not always, different from the original primary tumor in response to chemotherapy agents and ionizing X-irradiation. Although an exact mechanism is unknown, it is likely that "selective" pressures which eliminate large numbers of cells, in this case surgery, change tumor composition so that recurrent tumors may no longer be equivalent to the tumor mass that was originally excised. This suggests that treatment strategies should be planned accordingly.

Animals

Severe encephalopathy associated with ifosfamide administration in two children with metastatic tumors.

We studied two children with recurrent cancer, who during treatment with ifosfamide developed severe encephalopathy characterized by coma of several days duration. Ifosfamide was used as a single drug without mesna as an uroprotector. A 1-hour infusion of ifosfamide (1.8 g/m2) was given on days one and two of a planned 5-day course. Encephalopathy was associated with severe electroencephalographic abnormalities, e.g. slowing in delta range in one patient and electrographic seizures in another. Both, clinical and electroencephalographic features of encephalopathy were reversible.

Brain Neoplasms