RESUMO
More than 100 trillion symbiotic microorganisms constitutively colonize throughout the human body, including the oral cavity, the skin, and the gastrointestinal tract. The oral cavity harbors one of the most diverse and abundant microbial communities within the human body, second to the community that resides in the gastrointestinal tract, and is composed of >770 bacterial species. Advances in sequencing technologies help define the precise microbial landscape in our bodies. Environmental and functional differences render the composition of resident microbiota largely distinct between the mouth and the gut and lead to the development of unique microbial ecosystems in the 2 mucosal sites. However, it is apparent that there may be a microbial connection between these 2 mucosal sites in the context of disease pathogenesis. Accumulating evidence indicates that resident oral bacteria can translocate to the gastrointestinal tract through hematogenous and enteral routes. The dissemination of oral microbes to the gut may exacerbate various gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, and colorectal cancer. However, the precise role that oral microbes play in the extraoral organs, including the gut, remains elusive. Here, we review the recent findings on the dissemination of oral bacteria to the gastrointestinal tract and their possible contribution to the pathogenesis of gastrointestinal diseases. Although little is known about the mechanisms of ectopic colonization of the gut by oral bacteria, we also discuss the potential factors that allow the oral bacteria to colonize the gut.
Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Microbiota , Bactérias , Trato Gastrointestinal , Humanos , BocaAssuntos
Antineoplásicos Imunológicos/uso terapêutico , Soropositividade para HIV/complicações , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Evolução Fatal , Humanos , Ipilimumab/efeitos adversos , Metástase Linfática , Masculino , Melanoma/secundário , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Malignant Melanoma (MM) is characterized by a growing incidence and a high malignant potential. Besides well-defined prognostic factors such as tumour thickness and ulceration, the Mitotic Rate (MR) was included in the AJCC recommendations for diagnosis and treatment of MM. In daily routine, the identification of a single mitosis can be difficult on haematoxylin and eosin slides alone. Several studies showed a big inter- and intra-individual variability in detecting the MR in MM even by very experienced investigators, thus raising the question for a computer-assisted method. OBJECTIVE: The objective was to develop a software system for mitosis detection in MM on H&E slides based on machine learning for diagnostic support. METHODS: We developed a computer-aided staging support system based on image analysis and machine learning on the basis of 59 MM specimens. Our approach automatically detects tumour regions, identifies mitotic nuclei and classifies them with respect to their diagnostic relevance. A convenient user interface enables the investigator to browse through the proposed mitoses for fast and efficient diagnosing. RESULTS: A quantitative evaluation on manually labelled ground truth data revealed that the tumour region detection yields a medium spatial overlap index (dice coefficient) of 0.72. For the mitosis detection, we obtained high accuracies of above 83%. CONCLUSION: On the technical side, the developed iDermatoPath software tool provides a novel approach for mitosis detection in MM, which can be further improved using more training data such as dermatopathologist annotations. On the practical side, a first evaluation of the clinical utility was positive, albeit this approach provides most benefit for difficult cases in a research setting. Assuming all slides to be digitally processed and reported in the near future, this method could become a helpful additional tool for the pathologist.
Assuntos
Diagnóstico por Computador , Melanoma/patologia , Mitose , Neoplasias Cutâneas/patologia , Software , Coloração e Rotulagem , Humanos , Interface Usuário-ComputadorRESUMO
Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From 2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6 months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of 315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy (empirical or targeted, time point and antifungal agent at the physician's discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %, p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and 22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %), 4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related survival was not different in the three cohorts. Antifungal treatment in patients with AML who received azole prophylaxis resulted in the expected efficacy-importantly, prior posaconazole prophylaxis did not render subsequent antifungal treatment less effective than prior itraconazole prophylaxis.
Assuntos
Antifúngicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Pesquisa Empírica , Neutropenia Febril/tratamento farmacológico , Itraconazol/administração & dosagem , Triazóis/administração & dosagem , Idoso , Estudos de Coortes , Neutropenia Febril/diagnóstico , Neutropenia Febril/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Profilaxia Pós-Exposição/métodos , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do TratamentoRESUMO
PURPOSE: The purpose of this study was to report on the first experiences with freehand single-photon emission-computed tomography (freehand SPECT) in sentinel lymph node biopsy (SLNB) in patients with malignant melanoma. Freehand SPECT is a novel imaging modality combining gamma probes, surgical navigation systems, and emission tomography algorithms, designed to overcome some of the limitations of conventional gamma probes. METHODS: In this study 20 patients with malignant melanoma underwent conventional planar scintigraphy prior to surgery. In the operating room, the number and location of separable SLNs were detected first by a pre-incisional scan with freehand SPECT to render a 3D-image of the target site and afterwards by a scan with a conventional gamma probe. After SLNB another scan was performed to document the removal of all targeted SLNs. RESULTS: Planar scintigraphy identified 40 SLNs in 26 nodal basins. Pre-incisional freehand SPECT mapped 38 of these nodes as well as one additional node in one patient (95.0% node based sensitivity). The results of freehand SPECT were identical to those of planar scintigraphy in 25 basins, while it missed one basin (96.2% basin based sensitivity). In comparison, the gamma probe failed to detect 7 nodes in 4 basins (82.5% node based sensitivity and 84.6% basin based sensitivity). After resection freehand SPECT detected 9 remaining radioactive spots, two of whichwere resected as they matched the position of SLNs detected on preoperative planar scintigraphy. CONCLUSIONS: Freehand SPECT provides a real-time, intraoperative 3D-image of the radioactive labelled SLNs, facilitating their detection and resection.
Assuntos
Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Salas Cirúrgicas , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Tomografia Computadorizada por Raios XRESUMO
UNLABELLED: Due to historical aspects in some federal states in Germany rehabilitation of geriatric patients is organized in geriatric departments in hospitals (§ 109 SGB V). In other states rehabilitation of these patients is mainly realized in geriatric rehabilitation facilities outside hospital care after approval by the health insurance (§ 111 SGB V). Thus, it is of interest to compare both types of health care with respect to differences in population characteristics, resource utilization and outcome parameters (i.e., excess costs, rehospitalization, fracture risk and mortality) using a common geriatric indication, the ischemic stroke, as an example. METHODS: Claims data of the AOK (Local Health Care Fund) from seven federal states in Germany were used. Insured persons with a documented hospital stay with discharge diagnosis cerebral infarction/stroke (ICD-10 I63, I64, below denoted by "ischemic stroke") in 2007 (N=39,887) were included and allocated to the respective form of rehabilitative health care via the OPS (German procedure classification for inpatient procedures) procedure 8-550 (§ 109, N=1,272) or via admission to a geriatric rehabilitation unit within 1 month after hospital discharge (§ 111, N=2,200). All direct costs were ascertained and presented with and without costs of long-term care. Excess costs were calculated as the difference of costs between the first year after insult and the costs in the previous year. Excess costs in the 2 types of care were compared using multivariate quantile regression analysis. Risk of hospitalization (due to ischemic stroke or fracture) and risk of death in a 1-year follow-up was analysed using multivariate cox regression. RESULTS: Insured members treated according to health care type § 109 were somewhat older (mean: 81 vs. 80 years of age), more frequently female (72 vs. 67%), more often receiving long-term care (27 vs. 19%) and had more often documented sequelae after insult (>=4 diseases 39 vs. 28%). No significant differences in excess costs between both types of care were observed (quantile regression: 25%-percentile-comparison: p=0.49 and 0.11; median-comparison: p=0.99 and 0.13; 75%-percentile-comparison: p=0.13 and 0.30, with and without costs of long-term care, respectively). Moreover, no significant differences were observed related to the outcomes 'rehospitalization due to ischemic stroke' (hazard ratio - HR [95% confidence interval - CI])=1.12 [0.85-1.48], p=0.43) and death (HR [95% CI]=1.03 [0.88-1.20], p=0.75) in the multivariate model (reference: health care type § 111). Insured members in health care type § 109 had a significant lower risk of rehospitalization due to fracture (HR [95% CI]=0.61 [0.40-0.93], p=0.02). CONCLUSION: According to health care type § 109 and § 111, geriatric patients differ in certain characteristics such as gender, statutory care and documented sequelae after insult. Except for the outcome 'fracture', no significant differences between both types of care have been observed in the selected outcomes. Primary studies with more differentiated data collection may focus on specific treatment and on aims and achievements of rehabilitation.
Assuntos
Isquemia Encefálica , Fraturas Ósseas , Custos de Cuidados de Saúde/estatística & dados numéricos , Reembolso de Seguro de Saúde/economia , Tempo de Internação/economia , Programas Nacionais de Saúde/economia , Idoso de 80 Anos ou mais , Isquemia Encefálica/economia , Isquemia Encefálica/mortalidade , Isquemia Encefálica/reabilitação , Feminino , Fraturas Ósseas/economia , Fraturas Ósseas/mortalidade , Fraturas Ósseas/prevenção & controle , Alemanha/epidemiologia , Humanos , Reembolso de Seguro de Saúde/estatística & dados numéricos , Masculino , Programas Nacionais de Saúde/estatística & dados numéricos , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/mortalidade , Reabilitação do Acidente Vascular Cerebral , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Menopausal hormone therapy (MHT) is associated with an increased breast cancer risk in postmenopausal women, with combined estrogen-progestagen therapy posing a greater risk than estrogen monotherapy. However, few studies focused on potential effect modification of MHT-associated breast cancer risk by genetic polymorphisms in the progesterone metabolism. We assessed effect modification of MHT use by five coding single nucleotide polymorphisms (SNPs) in the progesterone metabolizing enzymes AKR1C3 (rs7741), AKR1C4 (rs3829125, rs17134592), and SRD5A1 (rs248793, rs3736316) using a two-center population-based case-control study from Germany with 2,502 postmenopausal breast cancer patients and 4,833 matched controls. An empirical-Bayes procedure that tests for interaction using a weighted combination of the prospective and the retrospective case-control estimators as well as standard prospective logistic regression were applied to assess multiplicative statistical interaction between polymorphisms and duration of MHT use with regard to breast cancer risk assuming a log-additive mode of inheritance. No genetic marginal effects were observed. Breast cancer risk associated with duration of combined therapy was significantly modified by SRD5A1_rs3736316, showing a reduced risk elevation in carriers of the minor allele (p (interaction,empirical-Bayes) = 0.006 using the empirical-Bayes method, p (interaction,logistic regression) = 0.013 using logistic regression). The risk associated with duration of use of monotherapy was increased by AKR1C3_rs7741 in minor allele carriers (p (interaction,empirical-Bayes) = 0.083, p (interaction,logistic regression) = 0.029) and decreased in minor allele carriers of two SNPs in AKR1C4 (rs3829125: p (interaction,empirical-Bayes) = 0.07, p (interaction,logistic regression) = 0.021; rs17134592: p (interaction,empirical-Bayes) = 0.101, p (interaction,logistic regression) = 0.038). After Bonferroni correction for multiple testing only SRD5A1_rs3736316 assessed using the empirical-Bayes method remained significant. Postmenopausal breast cancer risk associated with combined therapy may be modified by genetic variation in SRD5A1. Further well-powered studies are, however, required to replicate our finding.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Neoplasias da Mama/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Alelos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Feminino , Genótipo , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Pós-Menopausa , Progesterona/metabolismo , Fatores de RiscoRESUMO
BACKGROUND: Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer. METHODS: A single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC). RESULTS: Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95-0.99, P=4.6 × 10(-3)), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96-1.01, P=0.139). CONCLUSION: Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer.
Assuntos
Neoplasias da Mama/enzimologia , Predisposição Genética para Doença , Variação Genética , Fosfatidilinositol 3-Quinases/genética , Neoplasias da Mama/genética , Estudos de Casos e Controles , Classe I de Fosfatidilinositol 3-Quinases , Feminino , HumanosRESUMO
BACKGROUND: Sentinel lymph node biopsy (SLNB) in melanoma using one-dimensional gamma probes is a standard of care worldwide. Reports on the performance are claimed by most groups to successfully detect the SLNs during the surgical procedure in almost 100% of the patients. In clinical practice, however, several issues remain which are usually not addressed: the difficulty of intraoperative detection of deeply located nodes, SLN detection in obese patients or in the groin and the impossibility to make a scan of the entire wound after SLN resection to avoid false negative testing for eventually remaining SLNs. MATERIALS AND METHODS: The concept behind freehand SPECT is to combine a gamma probe as used for conventional radio-guided surgery with a tracking system as used in neurosurgical navigation. From this combination and a proper algorithm framework the 3D reconstruction of radioactivity distributions and displaying these intraoperatively is possible. CONCLUSION: In summary, the feasibility of freehand SPECT could be shown and provides an image-guided SLNB and a truly minimally invasive and optimized surgical procedure.
RESUMO
The incidence rates and relative risks for colorectal cancer (CRC) are higher in men than in women. Sex steroids may play a role in this gender-associated difference in CRC risk. This study was conducted to explore the relationship of single nucleotide polymorphisms (SNPs) in steroid hormone signaling (ESR1, ESR2, PGR, NR1I2, and SHBG), phase I- and II-metabolizing enzyme (COMT, HSD17B1, CYP1A1, CYP17A1, CYP1A2, CYP1B1, CYP2C9, CYP3A4, CYP2C19, and GSTP1), and hormone transporter (ABCB1) genes with the risk of CRC in German women and men, separately. From the population-based DACHS study (South Germany), 47 putatively functional SNPs were genotyped in 1798 CRC cases (746 women and 1052 men) and 1810 controls (732 women and 1078 men). Significant allele dose-response associations were observed with ESR2_rs1255998, ESR2_rs928554, HSD17B1_rs605059, and ABCB1_rs2229109 in women (P trend=0.004, 0.05, 0.03, and 0.05 respectively) and with ABCB1_rs1045642, ABCB1_rs9282564, and SHBG_rs6259 in men (P trend=0.01, 0.03, and 0.02 respectively). The ESR2_rs1255998_G allele showed the most significant association with risk for CRC in women, with a per-allele odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.88). This finding was replicated in an independent study from North Germany including 1076 female CRC cases and 1151 controls (OR=0.84, 95% CI 0.71-1.04), yielding a per-allele OR of 0.80 (95% CI 0.69-0.93, P trend=0.003) in the pooled sample. These findings implicate a role of ESR2 in the risk for developing CRC in women and suggest that HSD17B1, ABCB1, and SHBG genes may contribute to sex steroid-mediated effects on CRC development.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Neoplasias Colorretais/genética , Estradiol Desidrogenases/genética , Receptor beta de Estrogênio/genética , Receptores de Superfície Celular/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Catecol O-Metiltransferase/genética , Sistema Enzimático do Citocromo P-450/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores SexuaisRESUMO
An 81-year-old woman presented with a skin-colored, slowly growing tumor on her right lower eyelid. The diagnosis of mixed tumor of the skin was confirmed after excision and histologic examination of the tissue, which demonstrated a characteristic histology and immunohistochemistry. The mixed tumor of the skin is a usually benign neoplasm believed to originate in sweat glands. It is composed of epithelial cells set in a mesenchymal matrix, showing apocrine differentiation. Immunohistochemical staining is positive for cytokeratin, CEA, EMA and S100.
Assuntos
Adenoma Pleomorfo/diagnóstico , Neoplasias Palpebrais/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adenoma Pleomorfo/patologia , Adenoma Pleomorfo/cirurgia , Idoso de 80 Anos ou mais , Glândulas Apócrinas/patologia , Biomarcadores Tumorais/análise , Transformação Celular Neoplásica/patologia , Diagnóstico Diferencial , Neoplasias Palpebrais/patologia , Neoplasias Palpebrais/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND: The incidence of melanoma is still increasing in fair-skinned populations. At least 80% of patients have localised disease and expect a 5-year relative survival of >90%. PATIENTS AND METHODS: In 2003-2004, disease-free patients with localised melanoma were recruited from the Munich Cancer Registry to answer quality-of-life (QoL) questionnaires 2 years after treatment. RESULTS: A response rate of 72% was achieved from a total of 1085 distributed questionnaires. Hundred and seventeen questionnaires had to be excluded because of updated information about secondary tumour and progression events. Thus, questionnaires from 664 patients were evaluated. QoL scores in melanoma patients were essentially similar to those of a general population. Differences were detected between women and men concerning emotional and sexual functioning. Age and number of comorbidities were the strongest factors influencing most all aspects of QoL. Fifty percent of patients referred to deficits in communication with their doctors. CONCLUSIONS: Patients who overcome melanoma do not necessarily have a reduced QoL. Strategies used by these melanoma patients resulted in similar levels of coping as previous studies in comparable general populations. Nevertheless, doctor-patient communication was correlated with emotional and social functioning and should be emphasised in treatment and care of melanoma patients.
Assuntos
Melanoma/psicologia , Melanoma/terapia , Qualidade de Vida , Neoplasias Cutâneas/psicologia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Progressão da Doença , Emoções/fisiologia , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Comportamento Sexual/fisiologia , Neoplasias Cutâneas/patologia , Inquéritos e Questionários , Carga TumoralRESUMO
BACKGROUND: Ultraviolet (UV) A1 phototherapy is an effective anti-inflammatory treatment modality that influences fibroblast functions. OBJECTIVES: To document the effects of UVA1 treatment in patients with localized scleroderma (LS) in a retrospective study (at least 6 months after UVA1 treatment) and in a prospective study before and immediately after medium-dose UVA1 irradiation. METHODS: In total, 30 patients (retrospective study n = 17, prospective study n = 13) with LS receiving UVA1 phototherapy five times weekly (for 3-6 weeks) were investigated. Improvement was documented using standardized questionnaires and clinical evaluation (using modified Rodnan skin score, Cutometer and 7.5-MHz ultrasound measurements). Levels of collagen I and collagen III metabolites were measured in serum and urine. RESULTS: In the retrospective study, medium-dose UVA1 phototherapy had been performed 6 months-3 years earlier (cumulative dose 750-1400 J cm(-2); mean + or - SD number of irradiations 19.3 + or - 3.8). Fourteen of 17 patients (82%) reported an improvement in symptoms following UVA1 therapy. In the prospective study, skin elasticity increased in 77% of the patients following medium-dose UVA1 phototherapy (cumulative dose 750-1250 J cm(-2); mean + or - SD number of irradiations 20.8 + or - 4.0). 7.5-MHz ultrasound measurements showed a mean reduction of lesional skin thickness of 13% compared with skin thickness before UVA1 phototherapy. The ratio of deoxypyridinoline to creatinine was significantly elevated in about two-thirds of the patients. CONCLUSIONS: This open study showed a positive short- and long-term efficacy of UVA1 phototherapy in patients with LS, with a reduction in sclerotic plaques, an increase in skin elasticity and a reduction of lesional skin thickness. UVA1 phototherapy had a significant effect on collagen metabolism. UVA1 phototherapy can be regarded as a safe treatment modality for patients with LS.
Assuntos
Esclerodermia Localizada/radioterapia , Terapia Ultravioleta/métodos , Adulto , Idoso , Colágeno/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Esclerodermia Localizada/metabolismo , Índice de Gravidade de Doença , Resultado do Tratamento , Raios UltravioletaAssuntos
Granuloma Eosinófilo/complicações , Doença de Erdheim-Chester/complicações , Antígenos CD/análise , Antígenos CD1/análise , Antígenos de Diferenciação Mielomonocítica/análise , Granuloma Eosinófilo/diagnóstico , Doença de Erdheim-Chester/diagnóstico , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
In general, it is believed that the extraction of proteins from formalin-fixed paraffin embedded samples is not feasible. However, recently a new technique was developed, presenting the extraction of non-degraded, full length proteins from formalin fixed tissues, usable for western blotting and protein arrays. In the study presented here, we applied this technique to punch biopsies of formalin fixed tissues embedded in paraffin to reduce heterogeneity of the tissue represented in sections, and to ensure analysing mainly defined cellular material. Successful extraction was achieved even from very small samples (0.7 mm(3)). Additionally, we were able to detect highly glycosylated proteins and protein modification, such as phosphorylation. Interestingly, with this technique it is feasible to extract high quality proteins from 14 year old samples. In summary, the new technique makes a great pool of material now usable for molecular analysis with high throughput tools.
Assuntos
Fixadores/química , Formaldeído/química , Proteínas/isolamento & purificação , Antígenos de Neoplasias , Biópsia , Western Blotting , Caderinas/análise , Caderinas/isolamento & purificação , Eletroforese em Gel de Poliacrilamida , Estudos de Viabilidade , Congelamento , Humanos , Fígado/química , Fígado/cirurgia , Melanoma/química , Melanoma/cirurgia , Modelos Biológicos , Proteínas de Neoplasias , Inclusão em Parafina , Coloração pela Prata , Fixação de Tecidos , Proteínas Supressoras de Tumor/análise , Proteínas Supressoras de Tumor/isolamento & purificaçãoAssuntos
Neoplasias da Mama Masculina/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Mamilos , Neoplasias Cutâneas/diagnóstico , Idoso de 80 Anos ou mais , Biópsia , Neoplasias da Mama Masculina/patologia , Carcinoma Ductal de Mama/patologia , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica , Mamilos/patologia , Neoplasias Cutâneas/patologiaAssuntos
Dermatoses do Pé/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Fatores Imunológicos/uso terapêutico , Psoríase/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Etanercepte , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Photodynamic therapy (PDT) with topical application of either aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) is increasingly used for the treatment of actinic keratoses (AKs). Although PDT is a well-tolerated treatment, pain is the most severe side effect. Sixty-nine patients (mean age 69 years, 61 male, 8 female) suffering from multiple AKs on the scalp (field cancerization) were included in the study. PDT treatment was performed, using red light (Waldmann PDT 1200) with a light dose of 100 J/cm2 delivered at a dose rate of 160 mW/cm2. Either ALA or MAL were used as photosensitizer. Patients were asked to rate their pain on a scale from 0 to 10 (0 = no pain, 10 = unbearable pain). Upon reaching a score of 10 treatment was discontinued. Comparison of ALA and MAL in patients with AK revealed that MAL induced less pain than ALA. While 14% of the patients treated with MAL discontinued treatment before reaching the required light dose of 100 J/cm2, the number of patients treated with ALA who discontinued treatment reached 54%. PDT using MAL appears to be a better tolerated treatment for multiple AKs on the scalp compared to ALA-PDT. Differences in selectivity for tumor cells and transport of ALA in peripheral neurons may play a role.