Tumour volume as a predictor of necrosis after chemotherapy in Ewing's sarcoma.
(17/5419)
We studied the CT and MR scans, and the histology of 50 patients with primary Ewing's sarcoma of bone to determine the association between the change in tumour volume and necrosis after chemotherapy, and to ascertain their influence on prognosis. The mean age of the patients was 17 years. The limbs were involved in 40 and the axial bones in ten. The volume of the tumour at diagnosis varied from 31 to 1790 ml. There was a significant relationship between necrosis and the measured change in volume of the tumour after chemotherapy. Progression of the tumour despite chemotherapy was seen only in patients with necrosis of grades 4 to 6. Necrosis significantly influenced survival (p < 0.05), but the effect of change in volume was less significant. Change in volume of the tumour is a good predictor of necrosis induced by chemotherapy. Necrosis is a strong prognostic factor in Ewing's sarcoma. (+info)
Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD).
(18/5419)
Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg(-1) of BPD intravenously 5 min to 180 min before light treatment of 150 J cm(-2) 690 nm. Vascular response was monitored using intravital microscopy and tumour cure was monitored by following regrowth over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective targeting for damage. No acute changes were observed in vessels when light was given 180 min after BPD injection. Tumour regression after light treatment occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in animals given treatment 180 min after drug injection. The correlation between the timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction. (+info)
Bone pain palliation with 85Sr therapy.
(19/5419)
The aim of this retrospective study was to evaluate the efficacy of 85Sr in the palliation of metastatic bone pain. 85Sr decays by electron capture with a gamma emission of 514 keV and associated x-ray emissions of 10-15 keV; physical half-life is 64 d. METHODS: Between 1977 and 1992, 119 doses of 85Sr chloride (mean activity 335 MBq [9 mCi]) were intravenously administered to 108 patients with hyperalgic generalized bone metastases from prostatic carcinoma (52 patients), breast carcinoma (41) or other cancers (15). Pain, performance status, blood and urinary excretion values were investigated during follow-up, and survival time was recorded. Strontium bone scans were obtained up to 8 wk after injection to document isotope biodistribution and to estimate absorbed doses. RESULTS: At 12 wk, 72.2% of patients showed significant benefit from treatment, i.e., enhanced quality of life and pain relief; 49.1% became free of pain. These beneficial effects lasted from 1 to 36 mo (mean 4.3 mo). The best symptomatic improvement was seen in patients treated at an early stage of metastatic skeletal disease and in prostate cancer patients. No evidence of a significant dose-response relationship was found in the data analysis. The mean absorbed dose ratio of metastases to marrow was estimated at 8.2. We found no evidence that hematological toxicity was a major problem; however, all patients experienced a reduction in blood counts, especially in platelets. CONCLUSION: Systemic radionuclide therapy using 85Sr is a feasible, effective and well-tolerated palliative treatment in patients with refractory bone pain. We attained at least the same response rate as that reported with bone-seeking beta-emitting radionuclides such as 89Sr. The patients who benefited the most from 85Sr treatment were in an early stage of metastatic disease or had prostate cancer. Our clinical findings could not be linked to either the total injected activity of 85Sr or the estimated absorbed dose delivered to metastases. (+info)
186Re-etidronate in breast cancer patients with metastatic bone pain.
(20/5419)
The aim of this study was to evaluate the efficacy of 186Re-1,1-hydroxyethylidene diphosphonate (etidronate) in breast cancer patients with painful bone metastases. METHODS: Thirty patients with advanced breast cancer who had metastatic bone pain were treated with 186Re-etidronate using different dosages in a noncomparative, open-label study. Twenty-four patients were evaluated for efficacy (6 patients had incomplete datasets). Dosages varied from 1295 to 2960 MBq (35 to 80 mCi). Efficacy was evaluated according to the multidimensional pain model using a paper-and-pencil diary. The diary was kept twice daily for 8-10 wk (2 wk before through 6-8 wk after 186Re-etidronate treatment). Response was determined with a strict criteria, in which pain intensity (PI), medication index (MI) and daily activities (DA) were core determinants. Response was defined as: (a) Reduced PI > or = 5% while MI and DA were at least constant; or (b) Reduced PI <25% in combination with improvement of MI or DA > or = 25%, without worsening of either factor. Duration of response should always exceed a minimum of 2 wk. RESULTS: Fifty-eight percent (n = 14) of all patients reported a response. The maximum follow-up period was 8 wk. Duration of response ranged from 2 to 8 wk (mean 4 wk). Patients (14/24) not only experienced considerable pain reduction, but in 12 patients this was also accompanied by noteworthy reduction in MI (> or = 25%). No clear dose-response relationship was found. CONCLUSION: With strict pain assessment criteria, 186Re-etidronate showed a response of 58% in the palliative treatment of metastatic bone pain originating from breast cancer. (+info)
GLI gene expression in bone and soft tissue sarcomas of adult patients correlates with tumor grade.
(21/5419)
The GLI gene encodes a transcription factor harboring five zinc finger motifs that bind to DNA in a sequence-specific manner. The gene was originally identified because of its amplification in a human glioblastoma, and previous studies have shown it to be amplified in a significant proportion of mesenchymal tumors, such as childhood sarcomas. Here we evaluate GLI gene expression in bone and soft tissue sarcomas of adult patients. Samples from 40 patients (37 sarcomas and 3 benign mesenchymal tumors) and samples of 15 normal mesenchymal tissues were examined for GLI gene amplification and expression by Southern hybridization, reverse transcription-PCR of tissue RNA, and immunohistochemistry, using a new polyclonal GLI antibody developed against an epitope outside of the zinc finger region. In contrast to childhood sarcomas, amplification of the GLI gene was not observed in sarcomas of adult patients. Although GLI gene expression in sarcomas was significantly higher than that in normal mesenchymal tissues (P < 0.0001), the levels were very variable. Attempts to correlate the expression data with different pathophysiological parameters only showed a significant relationship to tumor grade. Based on these data, increased levels of GLI gene expression may be indicative of the aggressiveness of the tumor. (+info)
Severe combined immunodeficient-hu model of human prostate cancer metastasis to human bone.
(22/5419)
Commonly used in vivo models of prostate cancer metastasis include syngeneic rodent cancers and xenografts of human cancer in immunodeficient mice. However, the occurrence of osseous metastases in these models is rare, and in xenograft models, species-specific factors may limit the ability of human cells to metastasize to rodent bones. We have modified the severe combined immunodeficient (SCID)-human model to test the ability of circulating human prostate cancer cells to home to macroscopic fragments of human bone and other organs previously implanted into SCID mice. We have also compared the growth of human prostate cancer cells in various human and mouse tissue microenvironments in vivo. Macroscopic fragments of human fetal bone, lung, or intestine (16-22 weeks gestation) or mouse bone were implanted s.c. into male CB.17 SCID mice. Four weeks later, human prostate cancer cells were injected either i.v. via the tail vein (circulating cell colonization assay) or directly into the implanted tissue fragments transdermally (end organ growth assay). Tumor growth was followed for 6 weeks by palpation and magnetic resonance imaging. After 6 weeks, tumors were enumerated in implanted human and mouse organ fragments and native mouse tissue. Tumors were characterized by histology, immunohistochemistry, and chromosomal analysis. After i.v. injection, circulating PC3 cells successfully colonized implanted human bone fragments in 5 of 19 mice. Tumors were easily followed by palpation and imaging and had an average volume of 258 mm3 at autopsy. Histological examination revealed osteolysis and a strong desmoplastic stromal response, which indicated intense stromal-epithelial interaction. Bone tumors were subcultured, and chromosomal analysis demonstrated that the tumors were derived from the parental prostate cancer cell line. Microscopic tumor colonies were also found in a few mouse lungs after i.v. injection of PC3, DU145, and LNCaP cells, however the volume of the lung nodules was less than 1 mm3 in all of the cases. No colonization of human lung or intestine implants, the mouse skeleton, or other mouse organs was detected, demonstrating a species- and tissue-specific colonization of human bone by PC3 cells. Direct injection of 10(4) prostate cancer cells into human bone implants resulted in large tumors in 75-100% of mice. PC3 and DU145 bone tumors were primarily osteolytic, whereas LNCaP bone tumors were both osteoblastic and osteolytic. PC3 and LNCaP bone tumors showed a desmoplastic stromal response, which indicated intense stromal-epithelial interaction. All three of the cell lines formed tumors in implanted human lung tissue; however, the tumors were all < or = 10 mm3 in volume and showed minimal stromal involvement. No tumors formed after either s.c. injection or injection of cells into implanted mouse bone demonstrating both species- and tissue-specific enhancement of growth of human prostate cancer cells by human bone. The severe combined immunodeficient-human model provides a useful system to study species-specific mechanisms involved in the homing of human prostate cancer cells to human bone and the growth of human prostate cancer cells in human bone. (+info)
Management of differentiated thyroid cancer diagnosed during pregnancy.
(23/5419)
OBJECTIVE: To assess the outcome of thyroid cancer diagnosed during pregnancy. DESIGN: Retrospective analysis of patients diagnosed between 1949 and 1997 with thyroid cancer presenting during pregnancy. RESULTS: Nine women with a median age of 28 years were identified. A thyroid nodule was discovered by the clinician during routine antenatal examination in four cases, the remainder had noted a lump in the neck. In all patients, the nodule was reported to almost double in size during the pregnancy. One patient underwent subtotal thyroidectomy during the second trimester; eight were operated on within 3 to 10 months from delivery. Total thyroidectomy was performed in five and subtotal thyroidectomy in four. All tumours were well differentiated and ranged in size from 1 to 6 cm. OUTCOME: The median follow-up was 14 years (5-31 years). One patient relapsed locally requiring further surgery. One patient developed bone metastases dying 7 years after presentation; her planned treatment had been delayed because of an intervening pregnancy. Eight of the original cohort of patients are currently disease free. CONCLUSIONS: Differentiated thyroid cancer presenting in pregnancy generally has an excellent prognosis. When the disease is discovered early in pregnancy, surgery should be considered in the second trimester but radioiodine scans and treatment can be safely delayed until after delivery. In all cases, treatment should not be delayed for more than a year. (+info)
Poly(ADP-ribosyl)ation of p53 during apoptosis in human osteosarcoma cells.
(24/5419)
Spontaneous apoptosis in human osteosarcoma cells was observed to be associated with a marked increase in the intracellular abundance of p53. Immunoprecipitation and immunoblot analysis revealed that, together with a variety of other nuclear proteins, p53 undergoes extensive poly(ADP-ribosyl)ation early during the apoptotic program in these cells. Subsequent degradation of poly(ADP-ribose) (PAR), attached to p53 presumably by PAR glycohydrolase, the only reported enzyme to degrade PAR, was apparent concomitant with the onset of proteolytic processing and activation of caspase-3, caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP), and internucleosomal DNA fragmentation during the later stages of cell death. The decrease in PAR covalently bound to p53 also coincided with the marked induction of expression of the p53-responsive genes bax and Fas. These results suggest that poly(ADP-ribosyl)ation may play a role in the regulation of p53 function and implies a regulatory role for PARP and/or PAR early in apoptosis. (+info)