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Biomedical subjects

A Aguayo

Publications and source records attributed to A Aguayo.

At least 19 recordsLinked to original sources
PubMed2004

Why Ni3Al is an itinerant ferromagnet but Ni3Ga is not.

Ni3Al and Ni3Ga are closely related materials on opposite sides of a ferromagnetic quantum critical point. The Stoner factor of Ni is virtually the same in both compounds and the density of states is larger in Ni3Ga. Thus in Stoner theory it should be more magnetic, and in local-density approximation (LDA) calculations it is. However, experimentally it is a paramagnet, while Ni3Al is an itinerant ferromagnet. We show that critical spin fluctuations are stronger in Ni3Ga, due to weaker q dependence of the susceptibility, and this effect is enough to reverse the trend. The approach combines LDA calculations with Landau theory and the fluctuation-dissipation theorem using the same momentum cutoff for both compounds. The calculations provide evidence for strong, beyond LDA, spin fluctuations associated with the critical point in both materials, but stronger in Ni3Ga than in Ni3Al.

Journal Article↗
PubMed2001

Nonsurgical treatment of hepatocellular carcinoma.

While surgical resection and tumor ablation are the preferred therapies for hepatocellular carcinoma (HCC), these are available or appropriate in only a minority of patients. This reflects the usual comorbidity of severe underlying liver disease that either precludes surgery or makes the surgical approach extremely dangerous. Nonetheless, regional control of HCC is highly relevant and many regional strategies have been explored, including hepatic intra-arterial chemotherapy transarterial chemoembolization, lipiodol chemoembolization, radiation therapy, cryosurgery, percutaneous ethanol injection, and radiofrequency ablation. In addition, a variety of systemic chemotherapeutic agents have been tested in HCC, including various combinations of 5-fluorouracil, doxorubicin, epirubicin, etoposide, cisplatin, and mitoxantrone, as well as interferon, tamoxifen, capecitabine, thalidomide, and octreotide. Published data regarding these regional and systemic therapies will be discussed in this review.

Angiogenesis Inhibitors↗
PubMed2001

Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL).

Angiogenesis, a complex process tightly controlled by several molecules including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) along with their receptors, plays a major role in the growth and metastasis of solid tumors. The expression and production of VEGF and bFGF have been documented in numerous solid tumors and hematopoietic neoplasms. Having recently shown increased expression of cellular VEGF in the leukemic cells of patients with chronic lymphocytic leukemia (CLL) we decided to investigate the expression of angiogenic receptors Flt1 and Tie1. Levels of Tie1 and Flt1 proteins were measured in leukemic cells from 231 patients with B-cell CLL using Western blot analysis and solid-phase radioimmunoassay (RIA). A strong correlation was found between Flt1 and Tie1 levels and white blood cell count (WBC) and absolute lymphocyte counts. Levels of Flt1 but not Tie1 correlated with levels of cellular VEGF. Interestingly, Tie1 correlated well with Rai stage (P=0.04). Flt1 and Tie1 did not correlate with survival, although when we evaluated the patients with early disease (Rai stage 0-II), higher levels of Tie1 but not of Flt1 correlated with worse survival. These data suggest that Tie1 plays a role in the early stages of B-cell CLL and as the disease progresses, the tumor cells become independent from the effects of Tie1. Further studies are now needed to dissect the mechanisms responsible for this phenomenon.

Actuarial Analysis↗
PubMed2001

Nonsurgical treatment of hepatocellular carcinoma.

Given the poor prognosis of HCC and the therapeutic challenge posed by underlying liver cirrhosis, efforts and resources must be directed towards preventive strategies. Return on the investment in such research is likely to be greater than can be expected from treatment of advanced disease.

Carcinoma, Hepatocellular↗
PubMed2001

Liver cancer.

The prognosis of patients with HCC remains dismal. Even in the subgroups of patients who have the most favorable characteristics and are eligible for surgical resection, the 5-year survival rate is less than 25%. For patients with more advanced disease, the median survival time is less than 1 year. The good news in HCC research is that the disease can be prevented. In Taiwan, the rate of HCC in children aged 6 to 9 years decreased from 5.2 per million population before the neonatal vaccination program began in 1984 to 1.3 per million population in the first vaccinated cohort. Treatment of viral hepatitis with IFN may decrease the rates of long-term development of HCC. Other agents that may prevent second primary tumors following resection of HCC, such as polyprenoic acid and acylic retinoid, are also being investigated.

Africa South of the Sahara↗
PubMed2001

Plasma hepatocyte growth factor is a prognostic factor in patients with acute myeloid leukemia but not in patients with myelodysplastic syndrome.

Hepatocyte growth factor (HGF) is a potent angiogenic factor. The aim of our study was to evaluate plasma HGF levels and their prognostic significance in patients with newly diagnosed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The sandwich enzyme immunoassay technique was used to quantify HGF in stored samples obtained before treatment from patients with AML (59 patients) and MDS (42 patients) treated at The University of Texas MD Anderson Cancer Center. HGF levels were significantly higher in patients with AML or MDS than in healthy individuals (P < 0.0001). Higher HGF levels in both AML and MDS correlated significantly with white blood cell (P = 0.000001 for both groups) and monocyte counts (P = 0.0004 and 0.003, respectively), and with poor performance status (P = 0.03 and 0.001, respectively). Using Cox proportional hazard model and HGF levels as a continuous variable, plasma levels of HGF correlated with shorter survival of AML (P = 0.001), but not MDS (P = 0.34) patients. No significant correlation was observed between HGF levels and complete remission rate or duration. In the multivariate analysis HGF retained its significance as prognostic factor in AML (P = 0.02), along with age (P = 0.0005).

Acute Disease↗
PubMed2001

Significance of angiogenin plasma concentrations in patients with acute myeloid leukaemia and advanced myelodysplastic syndrome.

Human angiogenin is a potent inducer of angiogenesis. The association between angiogenin and cancer progression and poor outcome in solid tumours has been documented, but its significance in leukaemias has not been evaluated. We evaluated plasma angiogenin levels in 101 previously untreated patients with acute myeloid leukaemia (AML) (59 patients) and advanced myelodysplastic syndrome (MDS) (42 patients). Angiogenin levels were significantly higher in AML and advanced MDS patients than in healthy individuals (P < 0.00001). Angiogenin levels were also significantly higher in advanced MDS than in AML (P = 0.001). Higher levels of angiogenin correlated with prolonged survival periods in both AML and advanced MDS patients (P = 0.02 and 0.01 respectively). We found no correlation between angiogenin plasma level and various patient characteristics, including age, performance status, antecedent haematological disorder, haemoglobin, white blood cell and platelet counts, and poor prognosis cytogenetics. There was no significant correlation between angiogenin level and complete remission rate and duration in AML or advanced MDS patients. In multivariate analysis, angiogenin concentration retained its significance as a prognostic factor in AML (P = 0.03), together with age (P = 0.00007) and haemoglobin (P = 0.03).

Acute Disease↗
PubMed2000

Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes.

Angiogenesis has been associated with the growth, dissemination, and metastasis of solid tumors. The aims of this study were to evaluate the vascularity and the levels of angiogenic factors in patients with acute and chronic leukemias and myelodysplastic syndromes (MDS). The numbers of blood vessels were measured in 145 bone marrow biopsies and the levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis growth factor-alpha (TNF-alpha), tumor growth factor-alpha (TGF-alpha), and hepatocyte growth factor (HGF) were determined in 417 plasma samples. Except for chronic lymphocytic leukemia (CLL), vascularity was significantly higher in all leukemias and MDS compared with control bone marrows. The highest number of blood vessels and largest vascular area were found in chronic myeloid leukemia (CML). VEGF, bFGF, and HGF plasma levels were significantly increased in acute myeloid leukemia (AML), CML, CLL, chronic myelomonocytic leukemia (CMML), and MDS. HGF, TNF-alpha, and bFGF but not VEGF were significantly increased in acute lymphoblastic leukemia (ALL). TNF-alpha levels were significantly increased in all diseases except for AML and MDS. No significant increase was found in TGF-alpha in any leukemia or MDS. The highest plasma levels of VEGF were in CML, and the highest plasma levels of bFGF were in CLL. The levels of HGF were highest in CMML. These data suggest that vascularity and angiogenic factors are increased in leukemias and MDS and may play a role in the leukemogenic process.

Acute Disease↗
PubMed2000

Clinical relevance of intracellular vascular endothelial growth factor levels in B-cell chronic lymphocytic leukemia.

Strong evidence exists for an association between high vascular endothelial growth factor (VEGF) levels and poor prognoses in patients with solid tumors and acute leukemia. Using Western blot analysis and solid-phase radioimmunoassay, we measured cellular VEGF levels in B-cell chronic lymphocytic leukemia (CLL) samples from 225 patients and correlated these levels with disease characteristics and prognoses. The median VEGF level in CLL samples was 7.26 times the median level detected in normal peripheral blood mononuclear cells. Patients with lower levels of VEGF protein showed a trend toward shorter survival (P =.07). However, in a subgroup of CLL patients with good prognoses or early-stage disease (Rai stages 0-II, Binet stages A,B; beta2-M </= 2.8 mg/dL), lower levels of VEGF were associated with shorter survival times. For the entire group of patients, no correlation was found between VEGF levels and beta2-M levels or Rai and Binet stage. Most samples from patients with CLL expressed the 43-kd VEGF isoform in addition to the commonly expressed 45-kd isoform. It remains to be seen whether the expression of the 43-kd isoform is responsible for this reversed correlation with outcome. (Blood. 2000;96:768-770)

Adult↗
PubMed1999

Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia.

Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells. It has been associated with angiogenesis, growth, dissemination, metastasis, and poor outcome in solid tumors. To assess cellular VEGF levels and their prognostic significance in newly diagnosed acute myeloid leukemia (AML), we used a radioimmunoassay (RIA) to quantify VEGF levels in stored samples obtained before treatment from 99 patients with newly diagnosed AML treated at the MD Anderson Cancer Center from 1996 to 1998. Outcome in the 99 patients was representative of that observed in all patients seen at this institution with this diagnosis during these years, but the 99 patients had higher white blood cell (WBC) and blast counts than the other patients. Results of the RIA were confirmed by Western blot. There was a relationship between increasing VEGF levels and shorter survival (P =.01), as well as shorter disease-free survival, both from start of treatment and from complete response (CR) date. In contrast, there was no relationship between VEGF level and WBC or blast count, or between VEGF level and such established prognostic factors as age, cytogenetics, performance status, or presence of an antecedent hematologic disorder, and multivariate analysis indicated that VEGF was still prognostic for the above outcomes after accounting for these factors, as well as treatment. Our results suggest that at least in AML patients with higher WBC and blast counts, cellular VEGF level is an independent predictor of outcome.

Acute Disease↗
PubMed1999

Combination therapy with methotrexate, vincristine, polyethylene-glycol conjugated-asparaginase, and prednisone in the treatment of patients with refractory or recurrent acute lymphoblastic leukemia.

BACKGROUND: L-asparaginase in combination with methotrexate has synergistic antileukemic activity in a schedule-dependent fashion. A new preparation of L-asparaginase, polyethylene-glycol conjugated (PEG)-asparaginase, is a pharmacologically different formulation of L-asparaginase with distinct properties including a longer half-life and less immunogenic properties. METHODS: Patients with refractory or recurrent acute lymphoblastic leukemia (ALL) were treated with a combination of methotrexate (MTX), vincristine, PEG-asparaginase, and prednisone (MOAP). The treatment was comprised of MTX, 100 mg/m(2) intravenously (i.v.), over 15 minutes on Days 1 and 14; PEG-asparaginase, 2500 IU/m(2), with a maximum dose of 3750 IU i.v. approximately 4-6 hours after MTX on Days 1 and 14; vincristine, 1.4 mg/m(2) (maximum dose, 2 mg) i.v., over 15 minutes on Days 1, 7, and 14; and prednisone, 200 mg daily orally, on Days 1-5 and 14-19. RESULTS: Thirty-two patients with a median age of 34 years (range, 20-74 years) were treated. Eight patients (25%) had ALL that was refractory to prior therapy and 24 patients (75%) had recurrent disease. Seven patients (22%) achieved a complete remission (CR). Five patients (16%) died early due to infections. Features associated with a poor response were high pretreatment lactate dehydrogenase levels and Philadelphia chromosome positive disease. The median duration of CR was 16 weeks and the overall median survival after MOAP therapy was 12 weeks. Anaphylactic reactions were not observed during MOAP combination therapy. CONCLUSIONS: MOAP is an active regimen in patients with refractory or recurrent ALL. This regimen is well tolerated and is not associated with allergic reactions. However, further studies regarding the pharmacologic interaction of MTX with PEG-asparaginase are needed to optimize this regimen.

Adult↗
PubMed1999

Complete hematologic and cytogenetic response to 2-amino-9-beta-D-arabinosyl-6-methoxy-9H-guanine in a patient with chronic myelogenous leukemia in T-cell blastic phase: a case report and review of the literature.

BACKGROUND: T-cell lymphoid blastic phase (BP) transformation is rare in chronic myelogenous leukemia (CML). 2-amino-9-beta-D-arabinosyl-6-methoxy-9H-guanine (GW506U78), a prodrug of arabinosylguanine (ara-G), is effective in T-cell leukemias. METHODS: The authors present a case of a 48-year-old male with Philadelphia chromosome (Ph) positive CML and T-cell lymphoid BP after 17 months in the chronic phase. RESULTS: Plasma pharmacokinetic studies after an infusion of GW506U78 at a dose of 40 mg/kg showed GW506U78 concentrations of 60 microM, and a peak ara-G concentration of 260 microM in the plasma. Cellular ara-G triphosphate (ara-GTP) concentration in the peripheral blood T-lymphoblasts was 80 microM at the end of GW506U78 infusion and reached a maximum of 150 microM. The patient achieved a complete response that lasted 13 months. Severe neurotoxicity related to GW506U78 was observed. CONCLUSIONS: GW506U78 showed antileukemic activity against Ph positive T-cell BP CML. Neurotoxicity was dose-limiting in this patient. Treatment with GW506U78 and modulation of ara-GTP concentrations are therapeutic strategies that require further exploration in T-cell malignancies. Investigation of other dosing schedules may limit neurotoxicity.

Antineoplastic Agents↗
PubMed1994

[Hemobilia caused by ruptured hepatic artery aneurysm].

We report two patients with hemobilia caused by hepatic artery aneurism that ruptured to the biliary tract. In the first patient, the diagnosis was made during an exploratory laparotomy. In the second patient, the aneurism was diagnosed with a selective hepatic artery arteriography and embolized during the procedure. The evolution of both patients was satisfactory.

Adolescent↗
PubMed1975

Schwann cell internuclear distances in developing rat unmyelinated nerve fibers.

The interrelation of Schwann cells in developing rat cervical sympathetic trunk was studied by measuring distances between consecutive Schwann cell nuclei in teased unmyelinated nerve fiber bundles (Remak fibers). From 300 to 400 inter-nuclear Schwann cell distances (INDs) were measured at ten days and 2, 4, 5, 6, 8, 12, and 16 weeks after birth. Median INDs increased from 54mum at ten days to reach adult values (90mum to 100mum) at 16 weeks of age. Mean axonal diameters measured in the contralateral cervical sympathetic trunk increased from 0.57mum to 0.69mum during the same period. Developmental changes in median INDs of Schwann cells correlated significantly with age but did not parallel increases in axonal diameter.

Aging↗