Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Hypomethylation at H19DMR in penile squamous cell carcinoma is not related to HPV infection.

Penile squamous cell carcinoma (SCC) is a rare and aggressive tumour mainly related to lifestyle behaviour and human papillomavirus (HPV) infection. Environmentally induced loss of imprinting (LOI) at the H19 differentially methylated region (H19DMR) is associated with many cancers in the early events of tumorigenesis and may be involved in the pathogenesis of penile SCC. We sought to evaluate the DNA methylation pattern at H19DMR and its association with HPV infection in men with penile SCC by bisulfite sequencing (bis-seq). We observed an average methylation of 32.2% ± 11.6% at the H19DMR of penile SCC and did not observe an association between the p16INK4a+ (p = 0.59) and high-risk HPV+ (p = 0.338) markers with methylation level. The average methylation did not change according to HPV positive for p16INK4a+ or hrHPV+ (35.4% ± 10%) and negative for both markers (32.4% ± 10.1%) groups. As the region analysed has a binding site for the CTCF protein, the hypomethylation at the surrounding CpG sites might alter its insulator function. In addition, there was a positive correlation between intense polymorphonuclear cell infiltration and hypomethylation at H19DMR (p = 0.035). Here, we report that hypomethylation at H19DMR in penile SCC might contribute to tumour progression and aggressiveness regardless of HPV infection.

Ligas acadêmicas em saúde: uma revisão sistemática e proposta de checklist norteador de novos estudos / Academic leagues in health: a systematic review and proposed checklist to guide new studies

Resumo Introdução: As ligas acadêmicas (LA) são grupos organizados sem fins lucrativos que seguem os princípios do trinômio universitário (ensino, pesquisa e extensão) por discentes e profissionais orientadores, historicamente presentes em faculdades de Medicina, mas também difundidas em diversos cursos de saúde. No entanto, o conhecimento sobre as LA é limitado. Objetivo: Este estudo teve como objetivos realizar uma revisão sistemática sobre as LA de saúde no Brasil, analisar o perfil demográfico e atuação delas no país, e propor concomitantemente um checklist norteador para a redação de relatos de experiência sobre a temática. Método: O estudo consiste em uma revisão sistemática que adotou as orientações do PRISMA e utilizou como banco de dados a BVS e Medline. Realizaram-se a descrição de detalhes das LA, a evolução histórica, o perfil demográfico e a avaliação bibliométrica dos dados obtidos. Além disso, elaborou-se um checklist (Crelas) para orientar novos relatos de experiência de LA. Resultado: Foram selecionados 2.064 estudos, e incluíram-se 74 artigos em 20 anos de análise (2003-2022). O perfil das LA em saúde se alterou com o passar dos anos, chegando ao modelo atual pautado no tripé de atividades. Ainda assim, as LA são heterogêneas no país, concentradas em algumas regiões, especialmente no Sudeste. Ademais, observaram-se uma heterogeneidade dos estudos, ausência de uma revista central e carência de estudos quantitativos uni/multicêntricos que avaliassem o impacto das LA na formação dos estudantes. Conclusão: Ainda são necessários novos estudos sobre essa temática com o propósito de esclarecer a lacuna acerca das atividades desenvolvidas e seus impactos acadêmicos e sociais.

Abstract Introduction: Academic Leagues (ALs) are not-for-profit groups commonly organized by graduate students and advisors in Brazilian universities, that follow the principles of the academic triad (teaching, research, and service). Historically found in medical schools, they have also been widespread in several health courses. However, knowledge about ALs is limited. Objectives: To conduct a systematic review on academic health leagues in Brazil, analyze the demographic profile and performance of ALs in Brazil, proposing concomitantly a checklist guide for the writing of experience reports on the subject. Methods: The study consists of a systematic review following the PRISMA guidelines and using the BVS Health and Medline databases. Details of ALs, their historical evolution, demographic profile, and bibliometric evaluation of the obtained data were described. In addition, a checklist was developed to guide new reports on AL experiences. Results: A total of 2,064 studies were selected, with 74 articles included in 20 years of analysis (2003-2022). The profile of health ALs has changed over the years, reaching the current model based on the triad of activities. However, ALs are heterogeneous in Brazil, concentrated in some regions, especially in the Southeast. Moreover, the heterogeneity of the studies, absence of a central scientific journal, and lack of quantitative uni/multicentric studies that assess the impact of ALs on student education were observed. Conclusion: New studies within this theme are still necessary to clarify the activities developed and their academic and social impacts.

The relevance of ERG immunoexpression intensity for prostatic adenocarcinoma in radical prostatectomy of 635 samples.

Prostate cancer is the world's most frequently diagnosed malignancy in men. Recent work suggests that patients with high ERG expression intensity are significantly more likely to develop biochemical relapse and metastasis, and die of prostate cancer. The objective of this study was to determine the relationship between the intensity of ERG protein expression and the staging of prostate cancer and the formation of metastases in 635 samples. A retrospective cohort analysis was performed using immunohistochemistry reactions in tissue microarray samples taken from non-neoplastic and neoplastic prostate tissue from patients who underwent radical prostatectomies at a reference hospital from 2009 to 2016. For the ERG marker analysis, the samples were scored for the presence or absence of nuclear signals. Weak, moderate, or strong intensity of the nuclei of the observable tumor cells was considered to be positive markers. All told, 635 samples were evaluated, and the ERG expression was inconclusive in 9% of cases, while 30% were positive and 61% were negative. Of the samples with positive result: 25.8% were weak and focal, 53.2% were moderate, and 21% were strong. Finally, 21% of the cases with a positive ERG had a high Gleason score. Metastasis was detected in 41% of the patients who were ERG positive, and of these, the majority had moderate marking and were aged older than 60 years, although there was no statistically significant difference between the older and younger age groups. Patients with moderate to strong ERG staining had higher staging compared to the others, and no increase in metastasis was detected in patients with more intense ERG expression. More studies should be carried out to corroborate these results and to reach a consensus on the intensity and scoring of the expression levels of ERG markers.

Can mental practice adjunct in the recovery of motor function in the upper limbs after stroke? A systematic review and meta-analysis.

BACKGROUND: Studies indicate that mental practice can be an adjuvant rehabilitation, improving motor functions. AIM: To synthesize the evidence on the intervention with the mental practice for the rehabilitation of the upper limb after stroke in the context of a dependent task. METHODS: The review was registered on the PROSPERO with protocol number: CRD42020166624. We searched the PubMed, Medline, Embase, Central, PEDro, and Web of Science from randomized clinical trials from 1975 to 2022. A literature review was conducted with 13 studies that synthesized findings on mental practice such as adjuvant rehabilitation in the recovery of the upper limb after stroke based on Fugl-Meyer Assessment (FMA) Motor and action research arm test (ARAT) scores. RESULTS: The sample size was 232 were part of the intervention group and 180 of the control group. The findings no showed results in favor of mental practice after stroke accordingly to ARAT and FMA Motor scores (P > 0.05). CONCLUSION: Current evidence does not support the use of the mental practice to increase the recovery of the upper limb after stroke, although the evidence is conflicting for some aspects of the technique.

HPV infection and 5mC/5hmC epigenetic markers in penile squamous cell carcinoma: new insights into prognostics.

BACKGROUND: Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). RESULTS: The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33-3.38). CONCLUSIONS: P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis.

Race in public health dentistry: a critical review of the literature.

OBJECTIVE: To carry out a critical review of the literature on the use of race, color, and ethnicity in the field of public health dentistry. METHODS: A literature search was conducted in MEDLINE via PubMed for articles published between 2014 and 2019. Using a data extraction form, we collected information on (1) bibliographic characteristics of the selected papers; (2) race, color, and ethnicity of the study participants and their sociodemographic profiles; and (3) the extent to which the original publications followed the recommendations by Kaplan and Bennett (2003) on the use of race, color, or ethnicity in biomedical research. RESULTS: Our initial search identified 2,032 articles, 53 of which were selected for full-text examination and assessment following pre-established eligibility criteria. Around 60% (n = 32) of the included studies did not justify the use of race, color, or ethnicity in their analyses, and 9% (n = 5) took these variables as indicators of the participants' genetic makeup. On the other hand, 68% (n = 36) of the reviewed papers considered race, color, and ethnicity as risk markers - not risk factors - for adverse oral health outcomes, whereas 80% (n = 42) adjusted racial/ethnic inequities for a range of socioeconomic and demographic factors in statistical models. Only one study (2%) explicitly took race, color, or ethnicity as a contextually dependent dimension of the participants' identities. CONCLUSION: Our findings indicate that research on oral health inequities is often based on reductionist and stigmatizing conceptions of race, color, or ethnicity. Such harmful misconceptions should be replaced with anti-racist narratives in order to effectively address racial oral health inequities.

Race in public health dentistry: a critical review of the literature

ABSTRACT OBJECTIVE To carry out a critical review of the literature on the use of race, color, and ethnicity in the field of public health dentistry. METHODS A literature search was conducted in MEDLINE via PubMed for articles published between 2014 and 2019. Using a data extraction form, we collected information on (1) bibliographic characteristics of the selected papers; (2) race, color, and ethnicity of the study participants and their sociodemographic profiles; and (3) the extent to which the original publications followed the recommendations by Kaplan and Bennett (2003) on the use of race, color, or ethnicity in biomedical research. RESULTS Our initial search identified 2,032 articles, 53 of which were selected for full-text examination and assessment following pre-established eligibility criteria. Around 60% (n = 32) of the included studies did not justify the use of race, color, or ethnicity in their analyses, and 9% (n = 5) took these variables as indicators of the participants' genetic makeup. On the other hand, 68% (n = 36) of the reviewed papers considered race, color, and ethnicity as risk markers - not risk factors - for adverse oral health outcomes, whereas 80% (n = 42) adjusted racial/ethnic inequities for a range of socioeconomic and demographic factors in statistical models. Only one study (2%) explicitly took race, color, or ethnicity as a contextually dependent dimension of the participants' identities. CONCLUSION Our findings indicate that research on oral health inequities is often based on reductionist and stigmatizing conceptions of race, color, or ethnicity. Such harmful misconceptions should be replaced with anti-racist narratives in order to effectively address racial oral health inequities.

PMS2: a potential prognostic protein marker in oral squamous cell carcinoma / PMS2: un potencial marcador proteico de pronóstico en el carcinoma oral de células escamosas

Background: An increase in oral squamous cell carcinoma (OSCC) cases was observed despite the reduction inexposure to classic risk factors. Although the exact cause of this trend remains unknown, epigenetic factors couldbe contributing to an increased occurrence of these tumors. This study aims to assess the influence of PMS2 pro-tein immunoexpression on the prognosis of patients with OSCC.Material and Methods: This study comprised 76 cases of OSCC treated between 2011 and 2016. Immunohisto-chemical staining for PMS2 was performed. For evaluation, 10 fields per histological section were photographed ata 400x magnification and positively-stained cells were counted with Image J. Mann-Whitney and Kruskal-Wallistests were used to compare the immunolabeling pattern with the clinical-pathological and prognostic characteris-tics. Survival analysis was performed with Chi-square, Long-Rank Mantel-Cox and Cox regression tests (p<0.05).Results: An overexpression of PMS2 was observed in N0/1 tumors and in oral cancers found in unusual locations.In patients ≤60 years of age, high levels of PMS2 (>60%; p=0.041) were associated with low survival (p=0.029).In multivariate analysis, surgery combined with chemotherapy (p=0.030) and high PMS2 immunoexpression(p=0.042) significantly increased the risk of death for ≤60 years old patients Conclusions: The findings of this study indicate that PMS2 can be a potential prognostic protein marker in OSCCpatients 60 years of age and younger.(AU)

Mismatch Repair Proteins in Oropharyngeal Squamous Cell Carcinoma: A Retrospective Observational Study.

Cases of oropharyngeal squamous cell carcinoma are on the rise and the disease now ranks as the most common human papillomavirus-related cancer. Although risk factors have been extensively discussed in the literature, the role of the DNA mismatch repair system remains unanswered. To evaluate the impact of the DNA mismatch repair (MMR) protein immunostaining on the tumor progression and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). This retrospective observational study comprised 50 cases of OPSCC. Immunohistochemistry for MSH2, MSH6, PMS2, MLH1, Ki67, p16 and caspase-3 was performed. The expression of these proteins was assessed in surgical resection margins, primary tumor (PT), and lymph node metastasis (LNM) of p16+ and p16- OPSCC. Clinical-pathological involvement in immunostaining was evaluated with Kruskal-Wallis/Dunn or Mann-Whitney test, Wilcoxon test and Spearman's correlation. Overall survival (OS) was analyzed with Log-Rank Mantel-Cox and Cox regression. MSH6 and caspase-3 showed high expression in PT (p16+ and p16 -) and in LNM (p16+ and p16-), and high levels of MSH2 were found in LNM (p16+ and p16 -). An imbalance in MutSα also was observed. PMS2 and caspase-3 expression was associated with poor survival in p16- OPSCC and, in multivariate analysis, MSH2, MSH6 and MLH1 had the poorest prognostic impact in p16+ OPSCC. MMR protein immunostaining is involved in OPSCC progression, dissemination and prognosis. The overexpression of MMR proteins as a response to increased DNA mismatch caused by cell proliferation and MSH2, MSH6 and MLH1 proteins might constitute a prognostic marker in p16+ OPSCC.

How to structure an oncogenetics service for the public health system: Report of the implementation of the first service in Northeastern Brazil.

INTRODUCTION: Identifying carriers of genetic mutations that increase the risk of developing cancer allows to adopt timely risk-reducing strategies. However, due to the elevated cost of genetic testing, few oncogenetics services are available in the Brazilian public health care system, especially in economically disadvantaged areas. OBJECTIVE: To describe the implementation of an oncogenetics service for patients suspected of hereditary cancer syndromes (HBOC and HNPCC) at a philanthropic referral oncology hospital in Northeastern Brazil, funded by the Ministry of Health's National Oncology Care Support Program (PRONON). METHODS: The service was implemented with the PDCA method (Plan, Do, Check and Act). RESULTS: During the first year of operation (starting in August 2018), 675 individuals were examined, of whom 272 patients and 98 family members were submitted to genetic testing. This included the collection of 338 DNA samples of which 300 were sequenced. The analysis identified 48 (17.1%) mutations for HBOC and 19 (6.8%) for HNPCC. CONCLUSION: In one year, the oncogenetics service was able to benefit over 300 families by generating advanced molecular data which may be used for tailoring cancer prevention and management.

How does genetic testing influence anxiety, depression, and quality of life? A hereditary breast and ovarian cancer syndrome suspects trial.

BACKGROUND: Emotional distress associated with genetic testing for hereditary breast and ovarian cancer syndrome (HBOC) is reported to interfere with adherence to treatment and prophylactic measures and compromise quality of life. OBJECTIVES: To determine levels of anxiety, depression, and quality of life in patients tested for pathogenic BRCA1/2 mutations and identify risk factors for the development of adverse psycho-emotional effects. METHODS: Cross-sectional observational trial involving 178 breast or ovarian cancer patients from a referral cancer hospital in Northeastern Brazil. Information was collected with the Hospital Anxiety and Depression Scale (HADS) and the World Health Organization (WHO) Quality of Life (QoL) questionnaire (WHOQOL-BREF). RESULTS: Patients suspected of HBOC had higher levels of anxiety than depression. The presence of (probably) pathogenic BRCA1/2 mutations did not affect levels of anxiety and depression. High schooling, history of psychiatric disease, and use of psychotropic drugs were directly associated with high anxiety. High schooling was too inversely associated with QoL as such a breast tumor. Anxiety and depression were directly correlated and both reduced significantly QoL. CONCLUSION: Our results highlight the importance of psychological support and screening of risk factors for anxiety and depression and low QoL in HBOC patients at the time of testing.

Are pathogenic BRCA1 mutations associated with parotid mucoepidermoid carcinoma? A case report.

OBJECTIVES: To describe a patient with BRCA1 mutation, mucoepidermoid parotid, multiple breasts, and thyroid cancers. CASE REPORT: A women was diagnosed at 33-years-age with a triple-negative breast cancer (right breast), at 43-years-age with a triple-negative breast cancer in left breast and at 53-years-age with a primary papillary-thyroid carcinoma. At 55-years-age, she was diagnosed with a primary mucoepidermoid carcinoma in right parotid, and concomitantly, her right nipple was affected by Paget's disease and a recurrent carcinoma in right breast (HR + /HER2 = 3 +). At 57-years-age, after the recurrence of a triple-negative breast cancer (left breast), a geneticist evaluated the patient's family history, including one stomach, one non-smoking-related lung, and two smoking-related laryngeal cancers. Genetic testing revealed a BRCA1 mutation (Chr17:41:251.867). The patient's daughter (a non-cancer patient) tested negative for the mutation. Both remain under medical supervision. CONCLUSIONS: We suggest that BRCA1 mutations are associated with non-breast and non-ovarian cancers such as salivary gland cancer.

Evaluation of a one-piece soft convex ostomy appliance: a prospective, multicentre, open-label pilot study.

Leakage of stomal effluent is considered by people living with a stoma to be the key factor that negatively impacts their quality of life (QoL). This non-randomised pilot study evaluated the performance of a new stoma appliance, Flexima® Active O Convex in 40 ostomy patients with a flat, flush or slightly retracted stoma over a 14-day period. Leakage was reported for the wear time of each pouch by the patients. On 79% of occasions, the patient reported no leakage under the skin protector. The appliance was very well tolerated and the condition of the patients' peristomal skin was maintained throughout the study. The performance was rated as 'good' or 'very good' by most of the patients. The results of this study have shown that the design of this one-piece soft convex appliance can prevent leakage and protect peristomal skin by providing a safe seal around the stoma. It was also reported as being flexible and comfortable to wear.

The intricate interplay between MSI and polymorphisms of DNA repair enzymes in gastric cancer H.pylori associated.

Gastric cancer is the fourth most common type of cancer worldwide. Helicobacter pylori is a well-established risk factor and may cause injuries to genomic integrity through an inefficient DNA repair. This study aimed to examine the influence of polymorphisms in DNA repair enzymes using markers for microsatellite instability (MSI). Polymorphisms of DNA repair enzymes were detected by PCR-RFLP and MSI, by high resolution melt (HRM) analysis. Helicobacter pylori detection and genotyping were accomplished by PCR. MSI was observed in 47.5% of the cases and it was associated with the ERCC1 polymorphic allele, whereas MSI-H was associated with the XRCC3 heterozygous genotype. MSI was more frequent in intestinal gastric cancer (IGC), where it was associated with ERCC1 or RAD51 polymorphic alleles. Also, MSI-H was associated with the XRCC3 heterozygous. In diffuse gastric cancer (DGC), almost all of MGMT polymorphic genotype carriers showed MSI. Helicobacter pylori was positive in 94% of the cases and the most virulent strains were associated with MSI, mainly MSI-H. When the subtypes were considered, these associations were found only in the IGC and associated with more virulent strains. Among the cases with microsatellite instability, IGC showed a correlation between the XPD wild-type and the ERCC1 polymorphic allele, and all of them were infected by the most virulent strains. On the other hand, in DGC, the XPD polymorphic allele was correlated with the XRCC3 wild-type with no prevalence of H.pylori virulence. Our data demonstrated that polymorphisms in repair enzymes can interfere with the efficiency of the repair process, but it differs depending on the histological subtype and H.pylori involvement. Besides nucleotide excision repair, base excision repair and mismatch repair pathway, the homologous recombination are also involved.

Characterization of Gastric Cardia Tumors: Differences in Helicobacter pylori Strains and Genetic Polymorphisms.

BACKGROUND: Gastric cancer results from a multifactorial process and is one of the most common causes of death worldwide. These tumors can arise in the distal stomach (non-cardia) and in the cardia region, presenting different characteristics and frequency of occurrence worldwide. AIMS: To search for differences between tumors of different locations that could explain the presence of cardia tumors, considering Helicobacter pylori strains and genetic polymorphisms. MATERIALS AND METHODS: DNA was extracted from gastric adenocarcinoma tissue of 127 patients. Helicobacter pylori genes were detected by PCR, and polymorphisms by PCR-RFLP. RESULTS: Most of the tumors were located in non-cardia. The genotype 28152GA of XRCC1 showed an increase in risk of cardia tumors. In analysis performed considering gender, women carrying TNF-308GA genotype showed a decreased risk of non-cardia tumors, while in men the decreased risk of non-cardia tumors was associated with TNF-308GG genotype. Genotypes combinations showed that the SNPs RAD51 135G>C, XRCC3 18067C>T, and XRCC1 28152G>A had some combinations more frequent in cardia tumors, with an increased risk. Patients infected by cagE-positive strains presented a positive correlation with non-cardia tumors. CONCLUSION: The results showed some susceptibility differences between tumors of different locations. There was an increased risk relationship between three repair enzyme SNPs and cardia tumors, and the G allele of the cytokine gene TNF negatively influenced the development of non-cardia tumors. Helicobacter pylori strains seemed to be different in the cardia region, where they were less virulent than those located in the distal region of the stomach.

Effect of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in patients with colorectal cancer.

It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis.

The nebulin repeat protein Lasp regulates I-band architecture and filament spacing in myofibrils.

Mutations in nebulin, a giant muscle protein with 185 actin-binding nebulin repeats, are the major cause of nemaline myopathy in humans. Nebulin sets actin thin filament length in sarcomeres, potentially by stabilizing thin filaments in the I-band, where nebulin and thin filaments coalign. However, the precise role of nebulin in setting thin filament length and its other functions in regulating power output are unknown. Here, we show that Lasp, the only member of the nebulin family in Drosophila melanogaster, acts at two distinct sites in the sarcomere and controls thin filament length with just two nebulin repeats. We found that Lasp localizes to the Z-disc edges to control I-band architecture and also localizes at the A-band, where it interacts with both actin and myosin to set proper filament spacing. Furthermore, introducing a single amino acid change into the two nebulin repeats of Lasp demonstrated different roles for each domain and established Lasp as a suitable system for studying nebulin repeat function.

Effect of MLH1 -93G>A on gene expression in patients with colorectal cancer.

The DNA repair machinery plays a key role in maintaining genomic stability by preventing the emergence of mutations. Furthermore, the -93G>A polymorphism in the MLH1 gene has been associated with an increased risk of developing colorectal cancer. Therefore, the aim of this study was to examine the expression pattern and effect of this polymorphism in normal and tumour samples from patients with colorectal cancer. The MLH1 -93G>A (rs1800734) polymorphism was detected by PCR-RFLP in 49 cases of colorectal cancer. MLH1 expression was investigated using real-time quantitative PCR. The results indicate a significant decrease in MLH1 expression in tumour samples compared to their normal counterparts. The MLH1 gene was also significantly repressed in samples from patients who had some degree of tumour invasion into other organs. Similarly, those patients who were in a more advanced tumour stage (TNM III and IV) exhibited a significant reduction in MLH1 gene expression. Finally, the mutant genotype AA of MLH1 was associated with a significant decrease in the expression of this gene. This finding suggests that this polymorphism could increase the risk of developing colorectal cancer by a defective mismatch repair system, particularly through the loss of MLH1 expression in an allele-specific manner.

The photochemistry and photophysics of a series of alpha octa(alkyl-substituted) silicon, zinc and palladium phthalocyanines.

Photophysical and photochemical measurements have been made on a series of novel alpha octa(alkyl-substituted) silicon, zinc and palladium phthalocyanines for which the synthesis is outlined. Fluorescence quantum yields and lifetimes, triplet quantum yields and lifetimes and singlet delta oxygen quantum yields were measured in 1% v/v pyridine in toluene. The effects of varying central atom and addition of alkyl substituents relative to unsubstituted parent molecules, zinc phthalocyanine (ZnPc) and silicon phthalocyanine (SiPc), are discussed. All phthalocyanines studied exhibit absorption and emission maxima in the region of 680-750 nm with molar absorptivity of the Q-band ~10(5) M(-1) cm(-1). The series of compounds also exhibited triplet quantum yields of 0.65-0.95 and singlet oxygen quantum yields of 0.49-0.93.