Abstract In the search for alternatives to overcome the challenge imposed by drug resistance development in cancer treatment, the modulation of autophagy has emerged as a promising alternative that has achieved good results in clinical trials. Nevertheless, most of these studies have overlooked a novel and selective type of autophagy: chaperone-mediated autophagy (CMA). Following its discovery, research into CMA’s contribution to tumor progression has accelerated rapidly. Therefore, we now understand that stress conditions are the primary signal responsible for modulating CMA in cancer cells. In turn, the degradation of proteins by CMA can offer important advantages for tumorigenesis, since tumor suppressor proteins are CMA targets. Such mutual interaction between the tumor microenvironment and CMA also plays a crucial part in establishing therapy resistance, making this discussion the focus of the present review. Thus, we highlight how suppression of LAMP2A can enhance the sensitivity of cancer cells to several drugs, just as downregulation of CMA activity can lead to resistance in certain cases. Given this panorama, it is important to identify selective modulators of CMA to enhance the therapeutic response. treatment trials Nevertheless chaperonemediated chaperone mediated CMA. . (CMA) discovery CMAs s rapidly Therefore turn tumorigenesis targets review Thus LAMPA LAMP A drugs cases panorama response (CMA

Abstract Base and nucleotide excision repair (BER and NER) pathways are normally associated with removal of specific types of DNA damage: small base modifications (such as those induced by DNA oxidation) and bulky DNA lesions (such as those induced by ultraviolet or chemical carcinogens), respectively. However, growing evidence indicates that this scenario is much more complex and these pathways exchange proteins and cooperate with each other in the repair of specific lesions. In this review, we highlight studies discussing the involvement of NER in the repair of DNA damage induced by oxidative stress, and BER participating in the removal of bulky adducts on DNA. Adding to this complexity, UVA light experiments revealed that oxidative stress also causes protein oxidation, directly affecting proteins involved in both NER and BER. This reduces the cell’s ability to repair DNA damage with deleterious implications to the cells, such as mutagenesis and cell death, and to the organisms, such as cancer and aging. Finally, an interactome of NER and BER proteins is presented, showing the strong connection between these pathways, indicating that further investigation may reveal new functions shared by them, and their cooperation in maintaining genome stability.

OBJETIVO: Avaliar a qualidade das córneas processadas pelo Banco de Olhos de Sorocaba - SP e transplantadas fora do Hospital Oftalmológico de Sorocaba, bem como das córneas que tiveram reentrada no Banco de Olhos de Sorocaba durante o ano de 2007. MÉTODOS: Foram contatados os oftalmologistas que transplantaram córneas captadas pelo Banco de Olhos de Sorocaba fora do Hospital Oftalmológico de Sorocaba, bem como os que utilizaram córneas reentradas, a fim de colher as seguintes informações: período desde a captação da córnea até o transplante, transparência do tecido doador, tempo de transplante e falência primária. RESULTADOS: Trezentas e noventa e duas córneas tiveram saída do Banco de Olhos de Sorocaba ao longo do ano de 2007. Dessas, 6 retornaram ao Banco de Olhos de Sorocaba e foram transplantadas no Hospital Oftalmológico de Sorocaba, sendo que nenhuma foi rejeitada; todavia, 2 apresentaram alguma opacidade no eixo visual. Após tentativa de reunir informações a respeito das 386 córneas transplantadas fora do Hospital Oftalmológico de Sorocaba, obtiveram-se dados apenas de 48 transplantes. O tempo médio desde a captação até o transplante foi de 5,5 dias (1-13 dias), e o de seguimento médio pós-operatório, de 9,8 meses (4-15 meses). Três córneas desenvolveram falência primária, 3 evoluíram com opacidade no eixo visual, 1 apresentou ceratite infecciosa que necessitou de transplante tectônico; 1 paciente faleceu e 1 perdeu seguimento. As demais 39 córneas apresentavam-se transparentes. CONCLUSÃO: Por causa das dificuldades de reunir as informações dos pacientes transplantados em outros hospitais, torna-se difícil definir a qualidade das córneas liberadas pelo Banco de Olhos de Sorocaba. Assim, outras análises como as desse estudo são necessárias a fim de definir mudanças e rumos para estudos futuros sobre seleção e conservação das córneas doadas.

PURPOSE: To evaluate the quality of the corneas processed by Sorocaba Eye Bank (BOS) - SP and transplanted out of the Ophthalmology Hospital of Sorocaba (HOS), as well as the corneas that had re-entered in the BOS, being transplanted or not in the HOS, during the year of 2007. METHODS: Ophthalmologists that transplanted corneas processed by BOS outside of the Ophthalmology Hospital of Sorocaba were contacted, as well as those who had used re-entried corneas, to collect the following information: period from eye enucleation until transplant, transparency of the donated tissue, time of transplant and primary failure. RESULTS: During the year of 2007, Sorocaba Eye Bank distributed three hundred and ninety-two corneas for outside HOS. From these, six had returned to BOS and had been transplanted in the Ophthalmology Hospital of Sorocaba. From those, none was rejected; however, two presented some opacity in the visual axis. After attempt to congregate information regarding the 386 transplanted corneas outside HOS, data of only 48 keratoplasty were available. The average time from the enucleation until the keratoplasty was of 5.5 days (1-13 days), and of postoperative average follow-up, 9.8 months (4-15 months). Three corneas had developed primary failure; three presented opacity in the visual axis; one presented infectious keratitis, requiring therapeutic keratoplasty; a patient died and another one lost follow-up. The other 39 corneas did not present any problems until the time this study was ended. CONCLUSION: Because of the difficulties to congregate informations of the patients transplanted in other hospitals, it is difficult to define the quality of the distributed corneas by Sorocaba Eye Bank. Thus, other analysis are necessary in order to define changes and new directions for future studies on selection and preservation of donated corneas.

OBJETIVO: Avaliar aspectos pré e pós-operatórios em pacientes submetidos a implantes de drenagem. MÉTODOS: Foi realizado estudo retrospectivo, com pacientes submetidos a implante de drenagem no setor de glaucoma do Hospital Oftalmológico de Sorocaba no período de janeiro de 2004 a dezembro de 2006. No estudo foram avaliadas as seguintes características: sexo, idade, olho operado, tipo de glaucoma, número de cirurgias oculares anteriores, pressão intraocular prévia e após, conforme tempo de seguimento. Foram observadas a acuidade visual pré e pós-implante, o número de medicações antiglaucomatosas prescritas pós-implante, as principais complicações e reintervenções necessárias. RESULTADOS: Entre os 92 pacientes a proporção foi de 60 (65,3%) do sexo masculino e 32 (34,7%) do feminino. Os principais tipos de glaucoma foram: 38,9% (n=37) secundário a transplante de córnea e 25,3% (n=24) glaucoma neovascular. A média da pressão intraocular pré-implante foi de 32 (±11,29) mmHg e pós-implante foi de 18, (±8,16) mmHg em 95 (100%) pacientes, 15,00 (±11,00) mmHg em 95 (100%), 16 (±11,64) mmHg em 54 (55,7%) e 20 (±10,14) mmHg em 21 (21,6%) para o período de 2 meses, 6 meses, 1 ano e 2 anos, respectivamente. As complicações mais frequentes foram extrusão do implante (8,5%) e atalamia (5,4%). CONCLUSÃO: Observou-se evolução satisfatória nos pós-implantes, independente das diversas causas do glaucoma. Neste estudo foi encontrada redução significante da pressão intraocular 2 meses, 1 ano e 2 anos (p<0,05). As complicações tiveram ocorrência e evolução independente do tipo de glaucoma, número de cirurgias prévias, idade e sexo.

PURPOSE: To evaluate aspects of patients submitted to drainage implant procedures before and after surgery. METHODS: A retrospective study was done, with patients submitted to drainage implant procedures in the Glaucoma Sector of the Hospital Oftalmológico de Sorocaba, from January, 2004 to December, 2006. The following characteristics were evaluated: gender, age, treated eye, glaucoma type, number of previous ophthalmologic surgeries, previous intraocular pressure and check-ups. The visual acuity was observed before and after the implant, the number of glaucoma medications given after the implant, the main complications and the necessity of a second intervention. RESULTS: Among the 92 patients, 65.3% (n=60) were male and 34.7% (n=32) were female. The main types of glaucoma were 38.9% (n=37) due to cornea transplant and 25.3% (n=24) to neovascular glaucoma. The intraocular pressure average before implant was 32 (±11.29) mmHg and after implant it was 18 (±8.11) mmHg in 100% (n=95) eyes, 15 (± 10.89) mmHg in 100% (n= 95), 16 (±11.64) mmHg in 55.7% (n=54) and 20 (±10.31) mmHg in 21.6% (n=21) for the period of 2 months, 6 months, 1 and 2 years, respectively. The most frequent complications were implant migration (8.5%) and shallow anterior chamber (5.4%). CONCLUSION: A satisfactory evolution in the patients after implants, taking into consideration several causes of glaucoma. A significant reduction of intraocular pressure was found in the period of 2 months, at 1 and 2 years (p< 0.05). The complications occurred and progressed independent of the type of glaucoma, number of previous surgeries, age or gender.

OBJETIVO: Determinar a prevalência das alterações oculares em pacientes de hanseníase ativa ou inativa, acompanhados em serviço de referência. MÉTODOS: O estudo transversal constou de exame ocular e levantamento de dados demográficos e clínico-epidemiológicos, em serviço de referência da cidade de Rio Branco (Acre), no período de outubro de 2001 a abril de 2002. RESULTADOS: Foram examinados 254 pacientes, com média de idade de 41,9 anos; 70,1% do sexo masculino e 29,9% do feminino; 73,6% residentes da área urbana e 76,8% de formas multi e 23,2% de paucibacilares. Anormalidades de anexos oculares foram descritas em 49,6% (n=126) dos casos e do globo ocular em 39,4% (n=100) dos casos, sendo as mais freqüentes: hipoestesia corneana, catarata, madarose, manchas hipercrômicas, hipolacrimejamento e ceratite ponteada. As lesões oculares (74,4%) tiveram freqüências desiguais (r<0,0001), predominando entre aqueles com mais de 40 anos de idade (48,4% versus 26,0% nos de 40 anos ou menos), nos casos multibacilares (76,8% versus 23,2%), e nas pessoas com mais de cinco anos de duração da hanseníase (r<0,001). As alterações de globo ocular foram mais observadas em pacientes com tratamento específico concluído (r<0,05). CONCLUSÕES: A freqüência da morbidade ocular na hanseníase, em quase três quartos (74,4%) dos casos, foi semelhante à descrita na literatura para pacientes ambulatoriais de serviço de referência, e foi mais prevalente nas formas multibacilares da doença e em pacientes acima de 40 anos de idade.

PURPOSE: To determine the prevalence of eye lesions in patients with active and non active leprosy who are being accompanied in a reference center. METHODS: The transverse study consisted of ocular examinations and the study of demographic and clinical-epidemiological data, in the reference center in the city of Rio Branco, AC (Brazil). The study was conducted between October of 2001 and April of 2002. RESULTS: Two hundred fifty-four patients were examined, the average age was 41.9 years, 70.1% were males and 29.9% females; 73.6% were from the urban area, 76.8% were of the multibacillary form and 23.2% were of the paucibacillary form. Abnormalities of the ocular annexes were observed in 49.6% of the patients (n=126) and of the ocular globe in 39.4% (n=100), the most frequent being hypoesthesia of the cornea, cataract, madarosis, hiperchromic patches, hypolacrimation, and punctate keratitis. The eye lesions (74.4%) had unequal frequencies (r<0.0001), being predominant among those older than 40 years (48.4%, against 26.0% in those under 40 years of age), multibacillary form (76.8% against 23.2% in the paucibacillary form), and in those with a leprosy history of more than 5 years (76.8% against 23.2% leprosy history of less than 5 years). Ocular globe alterations were more frequent in patients who had concluded specific treatments (r<0.05). CONCLUSIONS: The frequency of ocular morbidity in these leprosy patients, in almost three quarters (74.4%) of those examined in the outpatient clinics, appeared similar to that described in literature and was more frequent in the multibacillary form of the disease and in patients over 40 years of age.