Simulating the folding of HP-sequences with a minimalist model in an inhomogeneous medium.

The phenomenon of protein folding is a fundamental issue in the field of the computational molecular biology. The protein folding inside the cells is performed in a highly inhomogeneous, tortuous, and correlated environment. Therefore, it is important to include in the theoretical studies the medium where the protein folding is developed. In this work we present the combination of three models to mimic the protein folding inside of an inhomogeneous medium. The models used here are Hydrophobic-Polar (HP) in 2D square arrangement, Evolutionary Algorithms (EA), and the Dual Site Bond Model (DSBM). The DSBM model is used to simulate the environment where the HP beads are folded; in this case the medium is correlated and is fractal-like. The analysis of five benchmark HP sequences shows that the inhomogeneous space provided with a given correlation length and fractal dimension plays an important role for correct folding of these sequences, which does not occur in a homogeneous space.

[Radiation-induced infiltrating transitional cell carcinoma]. / Tumor transicional infiltrante de urotelio radioinducido.

INTRODUCTION: The increased risk of developing a transitional cell carcinoma (TCC) among patients irradiated for other pathologies in a known fact, but many times forgotten due to its low incidence. Our aim is to review the association between radiotherapy (RT) and muscle-infiltrating TCC among our patients. MATERIAL AND METHODS: Clinical survey among our muscle-infiltrating TCC data base since 1975. Descriptive analysis of found cases. RESULTS: We found 5 patients who developed muscle-infiltrating TCC with a mean time of 19.2 years since radiotherapy (three of them more than 20 years and the other two less than 10 years). Three patients also developed other tumours or pathologies related to radiotherapy. Two of them had an upper tract muscle-infiltrating TCC and required nephroureterectomy. All of them had high risk TCC of the bladder and one developed distant metastasis. CONCLUSIONS: Patients under abdomino-pelvic RT and a prolongued follow-up, can be considered a risk group for developing muscle-infiltrating TCC. Thus, either micro or macrohaematuria or irritative symptoms should lead us to think in this possibility, demanding complete and exhaustive study to rule out TCC in all the urothelium.

[Adjuvant and salvage radiotherapy after radical prostatectomy]. / Tratamiento adyuvante y de rescate tras prostatectomía radical.

After radical prostatectomy is important to identify patients who have a high risk of microscopic residual disease without micrometastatic disease. Adjuvant RT, in retrospective studies, reduce the risk of recurrence and is more efficacious than salvage RT and can improve PSA relapse-free survival and should have an impact on long-term overall survival. The benefit of androgen suppression could be due to a synergistic interaction and may possibly eliminate occult systemic disease. Appropriate selection to identify subgroups of patients who may benefit from salvage RT, even for those patients at the highest risk; and whether some form of hormone ablation should accompany. To predict the biochemical failure and the risk of metastatic disease after salvage RT. We analyze the references to select an appropriate therapy. Improved outcomes will need to be tested in randomized trials.

Tratamiento adyuvante y de rescate tras prostatectomía radical / Adyuvant and salvage radiotherapy after radical prostatectomy

Tras la prostatectomía radical es importante identificar pacientes con alto riesgo de enfermedad microscópica residual en ausencia de enfermedad micrometastásica. La radioterapia adyuvante en estudios retrospectivos reduce las recurrencias locales y es más eficaz que la RT de rescate, aportando mejor supervivencia libre de recaída bioquímica y un potencial impacto en la supervivencia global. La supresión androgénica puede posiblemente eliminar la enfermedad oculta y aportar un efecto aditivo sobre el control local. Es posible identificar y seleccionar los pacientes que pueden beneficiarse de la Radioterapia de rescate, incluso los de alto riesgo. Se puede determinar la predicción de la progresión de PSA tras rescate con radioterapia y el riesgo de metástasis. Analizamos la bibliografía para un mejor enfoque terapéutico, basándonos en los datos actuales conocidos, a la espera de realización de nuevos ensayos clínicos (AU)

After radical prostatectomy is important to identify patients who have a high risk of microscopic residual disease without micrometastatic disease. Adyuvant RT, in retrospective studies, reduce the risk of recurrence and is more efficacious than salvage RT and can improve PSA relapse-free survival and should have an impact on long-term overall survival. The benefit of androgen suppresion could be due to a synergistic interaction and may possibly eliminate occult systemic disease. Appropiate selection to identify subgroups of patients who may benefit from salvage RT, even for those patients at the highest risk; and whether some form of hormone ablation should accompany. To predict the biochemical failure and the risk of metastasic disease after salvage RT. We analize the references to selection an appropiate therapy. Improves outcomes will need to be tested in randomized trials (AU)

Tumor transicional infiltrante de urotelio radioinducido / Radiation-induced infiltrating transitional cell carcinoma

Introducción; El incremento del riesgo de desarrollar un tumor de células transicionales (TCT) en los pacientes tratados con radioterapia y quimioterapia por otras patologías es un hecho conocido, pero muchas veces no tenido en cuenta por su rareza. Nuestro objetivo es revisar el comportamiento clínico de esta asociación en nuestro centro. Material y métodos; Nuestra casuística de TCT infiltrante con antecedentes de irradiación abdómino pélvica desde 1975. Análisis descriptivo de los casos encontrados con dichos antecedentes. Resultados; Encontramos 5 pacientes que desarrollaron TCT infiltrante a una media de 19,2 años tras radioterapia (tres de ellos con un seguimiento superior a 20 años y los dos restantes inferior a 10 años). Tres pacientes desarrollaron otro tipo de tumores o lesiones radio inducidas. En dos de ellos coexisten un TCT infiltrante detracto urinario superior que requirió nefroureterectomía. Los 5 casos desarrollaron TCT de vejiga de alto grado y un paciente desarrolló metástasis por TCT. Conclusiones; Los pacientes con irradiación abdómino pélvica con un seguimiento prolongado constituyen un grupo de riesgo para el desarrollo de TCT infiltrante. Por tanto, la presencia de hematuria debe alertarnos y exige completar los algoritmos validados para el diagnóstico de TCT en todo el urotelio (AU)

Introduction: The increased risk of developing a transitional cell carcinoma (TCC) among patients irradiated for other pathologies in a known fact, but many times forgotten due to its low incidence. Our aim is to review the association between radiotherapy (RT) and muscle-infiltrating TCC among our patients. Material and methods: Clinical survey among our muscle-infiltrating TCC data base since 1975. Descriptive analysis of found cases. Results: We found 5 patients who developed muscle-infiltrating TCC with a mean time of 19.2 years since radiotherapy (three of them more than 20 years and the other two less than 10 years). Three patients also developed other tumours or pathologies related to radiotherapy. Two of them had an upper tract muscle- infiltrating TCC and required nephroureterectomy. All of them had high risk TCC of the bladder and one developed distant metastasis. Conclusions: Patients under abdomino-pelvic RT and a prolongued follow-up, can be considered a risk group for developing muscle-infiltrating TCC. Thus, either micro or macrohaematuria or irritative symptoms should lead us to think in this possibility, demanding complete and exhaustive study to rule out TCC in all the urothelium (AU)

The FLF MADS box gene: a repressor of flowering in Arabidopsis regulated by vernalization and methylation.

A MADS box gene, FLF (for FLOWERING LOCUS F ), isolated from a late-flowering, T-DNA-tagged Arabidopsis mutant, is a semidominant gene encoding a repressor of flowering. The FLF gene appears to integrate the vernalization-dependent and autonomous flowering pathways because its expression is regulated by genes in both pathways. The level of FLF mRNA is downregulated by vernalization and by a decrease in genomic DNA methylation, which is consistent with our previous suggestion that vernalization acts to induce flowering through changes in gene activity that are mediated through a reduction in DNA methylation. The flf-1 mutant requires a greater than normal amount of an exogenous gibberellin (GA3) to decrease flowering time compared with the wild type or with vernalization-responsive late-flowering mutants, suggesting that the FLF gene product may block the promotion of flowering by GAs. FLF maps to a region on chromosome 5 near the FLOWERING LOCUS C gene, which is a semidominant repressor of flowering in late-flowering ecotypes of Arabidopsis.

Estrogen regulation of transforming growth factor-alpha in ovarian cancer.

Transforming growth factor alpha (TGFalpha) may be induced by estrogen in estrogen responsive systems and can contribute to the growth-modulatory effects of this hormone. To test whether TGFalpha contributes to estrogen-regulated growth in ovarian cancers, we have compared the effects of 17beta-estradiol (E2) and TGFalpha in a range of ovarian carcinoma cell lines. Addition of E2 to the estrogen receptor (ER)-positive cell lines (PE01, PE04 and PE01CDDP) produced a 2-4 fold increase in TGFalpha protein concentrations in media conditioned by the cells. Both E2 and TGFalpha stimulated the growth of the PE01 and PE04 lines and inhibited the growth of the PE01CDDP line. Furthermore, the E2-mediated growth effects could be reversed by an epidermal growth factor (EGF) receptor-targeted antibody. E2 also down-regulated EGF receptor expression in ER-positive cell lines. In a series of primary ovarian tumors, higher concentrations of ER were associated with an increased percentage of tumors expressing TGFalpha mRNA and a decreased percentage expressing EGF receptor protein. All these data are consistent with E2 increasing production of TGFalpha in ER-positive ovarian cancer and this in turn acting through the EGF receptor to modulate growth in an autocrine manner.