Catálogo de publicaciones - libros

Rapamycin and its analogs are versatile drugs with proven efficacy in cardiovascular and transplant medicine and with promising results in early cancer clinical trials. In specific tumor types, a select minority of patients likely will benefit from monotherapy. The challenge for the future will be to dissect further the molecular signaling pathways modulated by rapamycin in order to appreciate fully the molecular mechanisms underpinning sensitivity or resistance to mTOR inhibition. This understanding will provide insight into rational combinations of mTOR inhibitors with classic cytotoxic agents, radiation, and other molecularly targeted therapies.

Delegation of authorities is a common practice in various organizations. The way delegation is performed can be quite complicated. To capture possible delegation structures, the concept of is proposed, so that anyone can be convinced of who obtained delegation from whom in order to produce the final proxy signature. In this paper, we consider the delegation network for identity-based (ID-based) scenario. Since the public key is just a string denoting the user’s identity, certificate management is simplified. Proxy signature schemes have been devised to delegate signing authorities. We show that a trivial attempt of extending an existing ID-based proxy signature may result in an insecure scheme. After that we propose a building block of our ID-based delegation network, which is an ID-based proxy signature supporting batch verifications. Our proposed ID-based delegation network is flexible in the sense that the whole delegation network does not need to be known in advance. Our proposal is provably secure under the random oracle model.

The use of platinum compounds concomitant to radiotherapy is based on sound rationales and has resulted in development of several clinically successful combined modality regimens. Optimization of such regimens was accomplished mainly in clinical trials. Systematic work in a broader panel of preclinical tumor models suggests that more than additive effects can be obtained with fractionated radiotherapy when the drug is given shortly before radiation. Importantly, normal tissues do not exhibit the same degree of sensitization. With the advent of improved molecular characterization of tumor and host factors, it is hoped to identify the most suitable regimen for each individual patient. Nevertheless, it is emphasized that within a heterogeneous tumor (different molecular features of the cells, different perfusion, different drug sensitivity, changes of such factors over time) heterogenous drug concentrations and treatment effects have to be anticipated, which are very difficult to model or predict. In addition, each component of the treatment protocol might influence both the microenvironment of the tumor and the sensitivity to the other components, as exemplified by radiation-induced cisplatin resistance. These factors complicate the comparison and optimization of different drug administration protocols. The problems of drug access to the tumor cells, efflux, inactivation, toxicity, etc., are being addressed by advances in pharmacogenetics, delivery routes, development of new generation platinum compounds, and modifiers of metabolism and damage repair.

The last 20 years have yielded significant advances in the treatment of breast cancer. Adjuvant radiation therapy, chemotherapy, and hormonal therapy have all been shown to improve event-free and overall survival and are now part of the standard treatment in the management of breast cancer. Although there has been significant progress in determining the optimal combination and sequencing of these treatments, additional studies are still required to better integrate these therapies with each other. Furthermore, newer treatments, such as aromatase inhibitors and trastuzumab, also need to be integrated with conventional therapies to maximize their effectiveness and minimize their toxicity; therefore, the importance of the multidisciplinary management of breast cancer, with participation of the surgeons, radiation oncologists, medical oncologists, pathologists, and diagnostic radiologists, must once again be emphasized.

This is truly an exciting time in the management of breast cancer. Newer treatment techniques and modalities are constantly being developed. Coupled with the increasing knowledge about the biology of breast cancer, these treatments are allowing us to treat patients on a more individualized basis, with the aim of continually improving the rates of cure, as well as decreasing the risk of acute and late side effects.

The potential clinical benefit of exploiting tumor hypoxia by combining a hypoxia activated drug with conventional cancer therapy has yet to be realized in routine clinical practice. Despite this, the positive clinical results with the combination of the hypoxic cytotoxin tirapazamine with cisplatin in advanced non-small cell lung cancer and with chemoradiotherapy with advanced head and neck cancer demonstrate the potential of this approach. There is a good reason to expect that future drugs or strategies will do better: indeed advances made in experimental models identifying the determinants of the efficacy of these hypoxia-targeting compounds, together with other strategies to exploit tumor hypoxia, auger well for the future of this field.

The use of platinum compounds concomitant to radiotherapy is based on sound rationales and has resulted in development of several clinically successful combined modality regimens. Optimization of such regimens was accomplished mainly in clinical trials. Systematic work in a broader panel of preclinical tumor models suggests that more than additive effects can be obtained with fractionated radiotherapy when the drug is given shortly before radiation. Importantly, normal tissues do not exhibit the same degree of sensitization. With the advent of improved molecular characterization of tumor and host factors, it is hoped to identify the most suitable regimen for each individual patient. Nevertheless, it is emphasized that within a heterogeneous tumor (different molecular features of the cells, different perfusion, different drug sensitivity, changes of such factors over time) heterogenous drug concentrations and treatment effects have to be anticipated, which are very difficult to model or predict. In addition, each component of the treatment protocol might influence both the microenvironment of the tumor and the sensitivity to the other components, as exemplified by radiation-induced cisplatin resistance. These factors complicate the comparison and optimization of different drug administration protocols. The problems of drug access to the tumor cells, efflux, inactivation, toxicity, etc., are being addressed by advances in pharmacogenetics, delivery routes, development of new generation platinum compounds, and modifiers of metabolism and damage repair.

The potential clinical benefit of exploiting tumor hypoxia by combining a hypoxia activated drug with conventional cancer therapy has yet to be realized in routine clinical practice. Despite this, the positive clinical results with the combination of the hypoxic cytotoxin tirapazamine with cisplatin in advanced non-small cell lung cancer and with chemoradiotherapy with advanced head and neck cancer demonstrate the potential of this approach. There is a good reason to expect that future drugs or strategies will do better: indeed advances made in experimental models identifying the determinants of the efficacy of these hypoxia-targeting compounds, together with other strategies to exploit tumor hypoxia, auger well for the future of this field.

Delegation of authorities is a common practice in various organizations. The way delegation is performed can be quite complicated. To capture possible delegation structures, the concept of is proposed, so that anyone can be convinced of who obtained delegation from whom in order to produce the final proxy signature. In this paper, we consider the delegation network for identity-based (ID-based) scenario. Since the public key is just a string denoting the user’s identity, certificate management is simplified. Proxy signature schemes have been devised to delegate signing authorities. We show that a trivial attempt of extending an existing ID-based proxy signature may result in an insecure scheme. After that we propose a building block of our ID-based delegation network, which is an ID-based proxy signature supporting batch verifications. Our proposed ID-based delegation network is flexible in the sense that the whole delegation network does not need to be known in advance. Our proposal is provably secure under the random oracle model.

Rapamycin and its analogs are versatile drugs with proven efficacy in cardiovascular and transplant medicine and with promising results in early cancer clinical trials. In specific tumor types, a select minority of patients likely will benefit from monotherapy. The challenge for the future will be to dissect further the molecular signaling pathways modulated by rapamycin in order to appreciate fully the molecular mechanisms underpinning sensitivity or resistance to mTOR inhibition. This understanding will provide insight into rational combinations of mTOR inhibitors with classic cytotoxic agents, radiation, and other molecularly targeted therapies.

Delegation of authorities is a common practice in various organizations. The way delegation is performed can be quite complicated. To capture possible delegation structures, the concept of is proposed, so that anyone can be convinced of who obtained delegation from whom in order to produce the final proxy signature. In this paper, we consider the delegation network for identity-based (ID-based) scenario. Since the public key is just a string denoting the user’s identity, certificate management is simplified. Proxy signature schemes have been devised to delegate signing authorities. We show that a trivial attempt of extending an existing ID-based proxy signature may result in an insecure scheme. After that we propose a building block of our ID-based delegation network, which is an ID-based proxy signature supporting batch verifications. Our proposed ID-based delegation network is flexible in the sense that the whole delegation network does not need to be known in advance. Our proposal is provably secure under the random oracle model.