Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m2 during 8 weeks followed by weekly doxorubicin at 24 mg/m2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.

The impact on advanced economies of north-south trade in manufacturing and services

Many types of production are being transferred from the rich economies of the North to the poorer economies of the South. Such changes began in manufacturing but are now spreading to services. This paper provides estimates of their past and future impact on employment in the North. About 5 million manufacturing jobs have been lost over the past decade because of trade with low-wage economies. A similar number of service jobs may be lost to low-wage economies over the next decade. Although small compared to total employment, such losses may seriously harm certain localities or types of worker.

The new international financial crisis: causes, consequences and perspectives

The paper investigates the recent financial crisis within a historical and comparative perspective having in mind that it is ultimately a confidence crisis, initially associated to a chain of high risk loans and financial innovations that spread thorough the international system culminating with impressive wealth losses. The financial market will eventually recover from the crisis but the outcome should be followed by a different and more disciplined set of international institutions. There will be a change on how we perceive the widespread liberal argument that the market is always efficient, or at least, more efficient than any State intervention, overcoming the false perception that the State is in opposition to the market. A deep financial crisis brings out a period of wealth losses and an adjustment process characterized by price corrections (commodities and equity price deflation) and real effects (recession and lower employment), and a period of turbulences and end of illusions is in place.

Liberal versus neo-developmental convention to growth: why has Brazil shown a poor performance since the 1980s?

The main goal of our paper is to provide analytical arguments to explain why Brazil has not been able to restore its long-term capacity for economic growth, especially compared with its economy in the 1950-1979 period (7.3 per cent per year on average) or even with a select number of emerging economies in the 1980-2010 period(6.7 per cent per year on average, against 2.3 per cent per year on average in Brazil in the same period). We build our idea of convention to growth based on the Keynesian concept of convention. For our purposes, this concept could be briefly summarized as the way in which the set of public and private economic decisions related to different objectives, such as how much to produce and invest, how much to charge for products and services, how to finance public and private debt, how to finance research and development, and so on, are indefinitely - or at least until there is no change- carried out by the political, economic and social institutions. This analytical reference can be connected to the Neo-Schumpeterian National Innovation System (NIS) concept, which emphasizes not only institutions associated with science and technology per se, but also the complex interaction among them and other institutions. In this paper we identify two conventions to long-term growth in the last three decades in Brazil: the liberal and the neo-developmental. We show that the poor performance in the Brazilian economy in terms of real GDP growth from the 1980s on can be explained by a weak coordination between short-term macroeconomic policies and long-term industrial and technological policies. This weak coordination, in turn, can be associated with the prevalence of the liberal convention from the 1990s on, which has emphasized price stabilization to the detriment of a neo-developmental strategy whose primary goal is to sustain higher rates of growth and full employment in Brazil.

Democracy over governance

Varieties of institutional economics are available to evaluate varieties of capitalism. These methodologies dig behind preferences and technology to arrive at the ground on which agents make choices. The individual is at the foundation of these edifices, neoclassical and otherwise. Consequently, the denouement of all these models is that the market knows best in the absence of effective counterfactuals. A natural corollary is that the task of the government is to set effective mechanisms in place in order to approach the best outcomes. In contrast, we propose a framework which contends with the modern economy as an aggregate that evolves in historical time. Problems like effective demand failures are endemic to capitalist economies. Therefore, systematic State intervention is essential to their functioning. In particular, political economy teaches us that intervention must be in the interest of wage earners. In contrast to the earlier model, the fabric of norms and conventions that facilitate the growth and development of economies must emerge from the consciousness and practices of the working class.

Democracia consolidada e tamanho do Estado

Consolidated democracy and size of the State. Common sense suggests that the more consolidated democracies and advanced economies tend to be more efficient and produce smaller States. What is observed in practice, however, is a positive correlation between "democratic consolidation" and "tax burden" (as a proxy for"size of Government"). This finding, while not expressing any causal relationship between the two variables, is an evidence that a more republican and democratic State, as defined in Bresser-Pereira, must be able to provide, effectively and efficiently, broader public services with better quality. This is, in consolidated democracies, the State should not be small.

Globalization and democracy

ABSTRACTThe gathering momentum of globalization in the world economy has coincided with the spread of political democracy across countries. Economies have become global. But politics remains national. This essay explores the relationship between globalization and democracy, which is neither linear nor characterized by structural rigidities. It seeks to analyze how globalization might constrain degrees of freedom for nation states and space for democratic politics, and how political democracy within countries might exercise some checks and balances on markets and globalization. The essential argument is that the relationship between globalization and democracy is dialectical and does not conform to ideological caricatures.

O modelo liberal e republicano de liberdade: uma escolha disjuntiva?

Este artigo tem por objetivo apresentar duas maneiras de compreender a liberdade: a liberdade negativa do liberalismo, definida como a esfera do livre agir do indivíduo pela ausência de impedimentos externos, e que se norteia pelo paradigma jurídico dos direitos individuais; e a liberdade política do republicanismo, que se define como não-dominação e se orienta pelo paradigma das virtudes cívicas da cidadania. Um outro propósito consiste em mostrar que a oposição entre o ponto de vista jurídico-liberal e o republicanismo não está na aceitação ou na recusa da liberdade e dos direitos individuais. A divergência repousa, antes, sobre a maneira pela qual essa liberdade e direitos podem ser fundamentados: se pela via do individualismo e subjetivismo, que subordina a sociedade e o direito como instrumentos para a realização e proteção dos direitos individuais, ou pela via comunitarista e cívica. Desse modo, o conceito republicanismo de liberdade, sem abandonar a conquista liberal do pluralismo e da liberdade negativa, pode contribuir para uma efetiva ampliação e garantia dos princípios democráticos de uma sociedade moderna.

Razão e democracia: uso público da razão e política deliberativa em Habermas[ign] [title language="en"]Reason and democracy[ign]: [subtitle]Public use of reason and deliberative politics in Habermas

O objetivo do artigo é examinar como Habermas, orientado pela intuição normativa do uso público da razão, reconstrói uma concepção procedimental de democracia deliberativa, que, sem desconsiderar da dimensão estratégica e instrumental da esfera pública e da política, reformula a dimensão epistêmica da democracia: a aceitabilidade racional dos acordos políticos. Inicialmente, apresento brevemente a análise sociológica e histórica do conceito de esfera pública crítica, realizada em Mudança Estrutural da Esfera Pública (1962), para, em seguida, expor duas linhas de argumentação sobre o conceito de esfera pública e de política deliberativa, em Direito e Democracia (1992): a que se refere ao princípio de legitimação baseado na razão pública como uma reconstrução intersubjetiva e política do conceito kantiano de autonomia; e a que concerne aos aspectos essenciais da teoria crítica da sociedade fundada na distinção entre mundo da vida e sistema e a "tradução" sociológica e institucional do uso público da razão, nos conceitos de sociedade civil e esfera pública.