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Somatic/germline BRCA1/2 mutations (m)/(likely) pathogenic variants (PV) (s/gBRCAm) remain the best predictive biomarker for PARP inhibitor efficacy. As >95% of high-grade serous ovarian cancers (HGSOC) have a somatic TP53m, combined tumor-based BRCA1/2 (tBRCA) and TP53 mutation testing (tBRCA/TP53m) may improve the quality of results in somatic BRCAm identification and interpretation of the 'second hit' event, i.e., loss of heterozygosity (LOH). A total of 237 patients with HGSOC underwent tBRCA/TP53m testing. The ratio of allelic fractions (AFs) for tBRCA/TP53m was calculated to estimate the proportion of cells carrying BRCAm and to infer LOH. Among the 142/237 gBRCA results, 16.2% demonstrated a pathogenic/deleterious variant (DEL) gBRCA1/2m. Among the 195 contributive tumor samples, 43 DEL of tBRCAm (22.1%) were identified (23 gBRCAm and 20 sBRCAm) with LOH identified in 37/41 conclusive samples. The median AF of TP53m was 0.52 (0.01-0.93), confirming huge variability in tumor cellularity. Initially, three samples were considered as wild type with <10% cellularity. However, additional testing detected a very low AF (<0.05) in both BRCA1/2m and TP53m, thus reidentifying them as sBRCA1/2m. Combined tBRCA/TP53m testing is rapid, sensitive, and identifies somatic and germline BRCA1/2m. AF TP53m is essential for interpreting sBRCA1/2m in low-cellularity samples and provides indirect evidence for LOH as the 'second hit' of BRCA1/2-related tumorigenesis.
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Proteína BRCA1 , Neoplasias Ováricas , Humanos , Femenino , Proteína BRCA1/genética , Proteína BRCA2/genética , Mutación , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Mutación de Línea Germinal , Proteína p53 Supresora de Tumor/genéticaRESUMEN
This review aims to perform an updated bibliographical survey on the cultivation of microalgae in domestic wastewater with a focus on biotechnological aspects. It was verified that the largest number of researches developed was about cultures in microalgae-bacteria consortium and mixed cultures of microalgae, followed by researches referring to the species Chlorella vulgaris and to the family Scenedesmaceae. According to published studies, these microorganisms are efficient in the biological treatment of domestic wastewater, as well as in the production of high value-added biomass, as they are capable of biosorbing the organic and inorganic compounds present in the culture medium, thus generating cells with high levels of lipids, proteins, and carbohydrates. These compounds are of great importance for different industry sectors, such as pharmaceuticals, food, and also for agriculture and aquaculture. In addition, biomolecules produced by microalgae can be extracted for several biotechnological applications; however, most studies focus on the production of biofuels, with biodiesel being the main one. There are also other emerging applications that still require more in-depth research, such as the use of biomass as a biofertilizer and biostimulant in the production of bioplastic. Therefore, it is concluded that the cultivation of microalgae in domestic wastewater is a sustainable way to promote effluent bioremediation and produce valuable biomass for the biobased industry, contributing to the development of technology for the green economy.
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Chlorella vulgaris , Microalgas , Aguas Residuales , Biomasa , Biodegradación Ambiental , Monitoreo del Ambiente , BiocombustiblesRESUMEN
BACKGROUND: The main purposes of primary care-based pharmaceutical services (PHCPS) in Brazil are to provide free access to medicines and pharmaceutical care to patients. Several obstacles hinder achieving their goals; thus, MedMinas Project aimed to evaluate the PHCPS, the supply system, and the use of medicines. This paper reflects on our experience designing, planning, and conducting the project, describing the issues yielded in the field and lessons learned. METHODS: This work consists of a mixed-methods study conducted in Minas Gerais, Southeastern Brazil. We adopted the principles of Rapid Evaluation Methods, employing a multistage stratified sampling for the quantitative and a purposeful sampling for the qualitative components, respectively, and a documentary research. Data sources included individuals (patients and professionals), prescriptions, dispensed medicines, and policy documents collected between April and October 2019. The quantitative data described in this paper were analysed by descriptive statistics and the qualitative by Thematic Content Analysis. RESULTS: A total of 26 municipalities varying from 37,784 to 409,341 inhabitants were included. The field team spent, on average, 16 days in each location. We interviewed 1019 respondents, of which 127 were professionals and 892 patients. The participation rate varied from 92 to 100%, depending on the respondent subgroup. Most interviews lasted between 45 min and one hour. Fieldwork challenges included participants' enrolment, field team, interview processes, and project budget. The participants provided positive feedback and five main themes emerged from the interview experience (self-awareness, sense of gratitude, research value, access to findings, and benefits of the research). Additionally, we collected copies of 1072 documents and 2070 pieces of data from prescriptions filled and medicines dispensed at the PCP. CONCLUSION: We demonstrated the viability of conducting the MedMinas Project in an extensive geographic area within effective time frames that provided meaningful, high-quality data from multiple actors. The methods and lessons learned are valuable for researchers across various disciplines in similar urban settings in Brazil and other countries of low- and middle-income (LMIC).
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Servicios Farmacéuticos , Brasil , Humanos , Atención Primaria de SaludRESUMEN
BACKGROUND: Benefit of carboplatin and dose-dense weekly paclitaxel (ddCT) in first line treatment of ovarian cancer patients has been different in Western and Asian studies. In the present study we compare progression-free survival (PFS) of ddCT to three-weekly carboplatin and paclitaxel (CT) in first-line treatment of ovarian carcinoma in a single institution in a Western population. MATERIALS AND METHODS: We conducted a retrospective review of medical records from patients with ovarian carcinoma treated in a tertiary cancer center from 2007 to 2018. All patients treated with ddCT or CT in the first-line setting were included. Patients who received first-line bevacizumab were not included. PFS and overall survival (OS) were compared in a propensity score-matched cohort to address selection bias. Patients were matched according to age, ECOG performance status, CA 125, FIGO stage, residual disease, and histological subtype, in a 1:2 ratio. RESULTS: Five hundred eighty-eight patients were eligible for propensity score matching, the final cohort consisted of 69 patients treated with ddCT and 138 CT group. Baseline characteristics were well-balanced. After a median follow-up of 65.1 months, median PFS was 29.3 vs 20.0 months, favouring ddCT treatment (p = 0.035). In the multivariate cox regression ddCT showed a 18% lower risk of progression (HR 0.82, 95% CI 0.68-0.99, p = 0.04). Overall survival data is immature, but suggested better outcomes for ddCT (not reached versus 78.8 months; p = 0.07). CONCLUSION: Our retrospective study has shown superior PFS of ddCT over CT regimen in first-line treatment of ovarian carcinoma in a Western population not treated with bevacizumab.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Puntaje de Propensión , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Estudios RetrospectivosRESUMEN
Ovarian and breast cancers are currently defined by the main pathways involved in the tumorigenesis. The majority are carcinomas, originating from epithelial cells that are in constant division and subjected to cyclical variations of the estrogen stimulus during the female hormonal cycle, therefore being vulnerable to DNA damage. A portion of breast and ovarian carcinomas arises in the context of DNA repair defects, in which genetic instability is the backdrop for cancer initiation and progression. For these tumors, DNA repair deficiency is now increasingly recognized as a target for therapeutics. In hereditary breast/ovarian cancers (HBOC), tumors with BRCA1/2 mutations present an impairment of DNA repair by homologous recombination (HR). For many years, BRCA1/2 mutations were only screened on germline DNA, but now they are also searched at the tumor level to personalize treatment. The reason of the inactivation of this pathway remains uncertain for most cases, even in the presence of a HR-deficient signature. Evidence indicates that identifying the mechanism of HR inactivation should improve both genetic counseling and therapeutic response, since they can be useful as new biomarkers of response.
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Neoplasias de la Mama/genética , Carcinogénesis , Daño del ADN , Reparación del ADN , Recombinación Homóloga , Neoplasias Ováricas/genética , Antineoplásicos/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Ciclo Celular , Femenino , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Humanos , MutaciónRESUMEN
BACKGROUND: Brain metastasis (BM) is a rare event in ovarian cancer patients. The current prognostic scores that have been used for other tumors do not account for specific characteristics of ovarian cancer, such as platinum sensitivity. METHODS: This retrospective cohort study examined patients with ovarian carcinoma and BM who were treated at a single institution from January 2007 to December 2017. Clinical data on the diagnosis of BM and follow-up were collected. Cox regression was used to evaluate prognostic factors for overall survival (OS). RESULTS: Of 560 patients, 26 presented with BM. Eight patients were treated with surgery, 15 with whole-brain radiotherapy (RT), and 5 with stereotactic RT, and 4 patients received systemic treatment at the diagnosis of BM. The median OS was 10.8 months. The following factors were associated with OS: platinum-sensitive recurrence (HR 0.34, 95% CI 0.12-0.99; p = 0.049), higher number of previous treatment lines (HR 1.57, 95% CI 1.12-2.19; p = 0.008), ECOG performance status (HR 2.52, 95% CI 1.24-5.09; p = 0.010), and longer interval from initial diagnosis to BM (p = 0.025). Notably, the number of brain metastasis, the largest tumor size, and progression outside of the CNS were not related to survival. Platinum sensitivity was not associated with any of the classic prognostic factors in brain metastasis patients such as number or size of brain metastasis or disease progression outside the CNS strengthening the hypothesis of the importance of platinum sensitivity to the prognosis of ovarian cancer patients with BM. CONCLUSIONS: The factors related to the biological behavior of the ovarian cancer such as platinum sensitivity at the time of BM diagnosis, fewer number of previous treatment lines and interval from initial diagnosis were associated with survival in ovarian cancer patients with BM, while factors that are usually related to survival in BM in other cancers were not associated with survival in this cohort of ovarian cancer patients. The small number of patients did not allow us to exclude the prognostic role of these former factors that were not associated with survival in the present cohort.
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Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Neoplasias Ováricas/tratamiento farmacológico , Compuestos de Platino/administración & dosificación , Anciano , Antineoplásicos/uso terapéutico , Irradiación Craneana , Femenino , Humanos , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Compuestos de Platino/uso terapéutico , Pronóstico , Análisis de Regresión , Estudios Retrospectivos , Tamaño de la Muestra , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The widespread use of next generation sequencing for clinical testing is detecting an escalating number of variants in noncoding regions of the genome. The clinical significance of the majority of these variants is currently unknown, which presents a significant clinical challenge. We have screened over 6,000 early-onset and/or familial breast cancer (BC) cases collected by the ENIGMA consortium for sequence variants in the 5' noncoding regions of BC susceptibility genes BRCA1 and BRCA2, and identified 141 rare variants with global minor allele frequency < 0.01, 76 of which have not been reported previously. Bioinformatic analysis identified a set of 21 variants most likely to impact transcriptional regulation, and luciferase reporter assays detected altered promoter activity for four of these variants. Electrophoretic mobility shift assays demonstrated that three of these altered the binding of proteins to the respective BRCA1 or BRCA2 promoter regions, including NFYA binding to BRCA1:c.-287C>T and PAX5 binding to BRCA2:c.-296C>T. Clinical classification of variants affecting promoter activity, using existing prediction models, found no evidence to suggest that these variants confer a high risk of disease. Further studies are required to determine if such variation may be associated with a moderate or low risk of BC.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Mutación de Línea Germinal , Regiones Promotoras Genéticas , Regiones no Traducidas 5' , Edad de Inicio , Proteína BRCA1/química , Proteína BRCA1/metabolismo , Proteína BRCA2/química , Proteína BRCA2/metabolismo , Factor de Unión a CCAAT/metabolismo , Línea Celular Tumoral , Femenino , Predisposición Genética a la Enfermedad , Humanos , Células MCF-7 , Factor de Transcripción PAX5/metabolismo , Unión ProteicaRESUMEN
Myositis ossificans (MO) is an uncommon tumor characterized by a rapidly growing mass following a history of local trauma. Few cases of MO affecting the breast have been reported, and some were misdiagnosed as primary osteosarcoma of the breast or metaplastic breast carcinoma. The following case report presents a patient with a growing breast lump whose core biopsy result was suspicious for breast cancer. MO was diagnosed after analysis of the mastectomy specimen. This case highlights the importance of MO as a differential diagnosis of a growing soft-tissue mass after trauma to avoid unnecessary overtreatment. Keywords: Myositis Ossificans, Osteosarcoma, Breast Cancer, Mastectomy, Heterotopic Ossification © RSNA, 2023.
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Plants have long been used in traditional medicine to treat illnesses. Nevertheless, their chemical diversity requires studies to establish the extract dosage and its safe use. Pseudobombax parvifolium, an endemic species of the Brazilian Caatinga biome, is commonly used in folk medicine, due to its anti-inflammatory properties related to cellular oxidative stress; however, its biological properties have scarcely been studied. In this study, we chemically characterized the P. parvifolium hydroalcoholic bark extract (EBHE) and evaluated its cytotoxic, mutagenic, and preclinical aspects, as well as its antioxidant effect. Our phytochemical analysis revealed a significative total polyphenol content and identified loliolide for the first time in this species. Cytotoxicity, mutagenicity, and acute oral and repeated dose indicated no toxic effects on cell culture, Drosophila melanogaster, and Wistar rat exposure to different EBHE concentrations, respectively. Furthermore, we observed a significant decrease in lipid peroxidation and a mild hypoglycemic and hypolipidemic effect with repeated oral dosing of EBHE. Although there were no significant changes in glutathione content, we did observe a significant increase in superoxide dismutase at a dose of 400 mg/kg and in glutathione peroxidase at doses of 100, 200, and 400 mg/kg. These findings suggest that EBHE has potential as a source of bioactive molecules, and it can be used safely in traditional medicine and in the development of herbal medicines for application in the public health system.
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Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive condition that is associated with the SMARCA4 mutation and has a dismal prognosis. It is generally diagnosed in young women. Here, we report a case of a young woman with SCCOHT harboring a rare molecular finding with a highly aggressive biological behavior. The patient had a somatic SMARCB1 mutation instead of an expected SMARCA4 alteration. Even though the patient was treated with high-dose chemotherapy followed by stem cell transplantation, she evolved with disease progression and died 11 months after her first symptoms appeared. We present a literature review of this rare disease and discuss the findings in the present patient in comparison to expected molecular alterations and options for SCCOHT treatment.
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Carcinoma de Células Pequeñas , Neoplasias Pulmonares , Neoplasias Ováricas , Tumor Rabdoide , Proteína SMARCB1 , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/terapia , ADN Helicasas/genética , Resultado Fatal , Femenino , Humanos , Mutación , Proteínas Nucleares/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Ovario/patología , Tumor Rabdoide/genética , Tumor Rabdoide/patología , Tumor Rabdoide/terapia , Proteína SMARCB1/genética , Factores de Transcripción/genéticaRESUMEN
This study was conducted to evaluate the phenolic composition, toxicity, and antimicrobial activity of Licania rigida Benth, an underexploited wild Licania species. L. rigida leaf fractions (ethyl alcohol and ethyl acetate) were analyzed for their phenolic compound and flavonoid total, and high-performance liquid chromatography/ultraviolet spectra chromatographic profiles. Regarding the extract biological effects, toxicity was measured by acute oral toxicity in Wistar rats, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method, and apoptosis indicators with DAPI in VERO cells, whereas well-agar diffusion and broth microdilution assays were applied to evaluate the antimicrobial ability. The phytochemical analysis resulted in significant amounts of phenolic compounds and total flavonoids in the extract and fraction, with flavonol-3-O-glycosylates as the main constituent. Regarding the extract and fraction antimicrobial activity, the results showed a significant effect against gram-positive bacteria and fungi, among which Staphylococcus epidermidis and Candida krusei displayed more susceptibility. No toxicity effects were observed in animals. Concerning the cytotoxicity assay, only the highest dose tested exhibited a minimal toxic effect on the analyzed cell lines. These results are relevant considering the increase of multiresistant microorganisms to conventional treatments applied. Therefore, investigating the pharmacological properties of the genus Licania is promising in the search for new sources of antimicrobial compounds.
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Antiinfecciosos , Chrysobalanaceae , Animales , Antibacterianos , Antiinfecciosos/toxicidad , Antioxidantes , Chlorocebus aethiops , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/toxicidad , Ratas , Ratas Wistar , Células VeroRESUMEN
At least 10% of the BRCA1/2 tests identify variants of uncertain significance (VUS) while the distinction between pathogenic variants (PV) and benign variants (BV) remains particularly challenging. As a typical tumor suppressor gene, the inactivation of the second wild-type (WT) BRCA1 allele is expected to trigger cancer initiation. Loss of heterozygosity (LOH) of the WT allele is the most frequent mechanism for the BRCA1 biallelic inactivation. To evaluate if LOH can be an effective predictor of BRCA1 variant pathogenicity, we carried out LOH analysis on DNA extracted from 90 breast and seven ovary tumors diagnosed in 27 benign and 55 pathogenic variant carriers. Further analyses were conducted in tumors with PVs yet without loss of the WT allele: BRCA1 promoter hypermethylation, next-generation sequencing (NGS) of BRCA1/2, and BRCAness score. Ninety-seven tumor samples were analyzed from 26 different BRCA1 variants. A relatively stable pattern of LOH (65.4%) of WT allele for PV tumors was observed, while the allelic balance (63%) or loss of variant allele (15%) was generally seen for carriers of BV. LOH data is a useful complementary argument for BRCA1 variant classification.
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Developing robust systems for cancer care delivery is essential to reduce the high cancer mortality in small island developing states (SIDS). Indigenous data are scarce, but community-based cancer research can inform care in SIDS where formal research capacity is lacking, and we describe the experiences of cancer survivors in Saint Lucia in accessing health services. Purposive and snowball sampling was used to constitute a sample of survivors for interviews. Subjects were interviewed with a questionnaire regarding socio-demographics, clinical characteristics, health services accessed (physicians, tests, treatment), and personal appraisal of experience. We recruited 50 survivors (13 men, 37 women). Only 52% of first presentations were with general practitioners. The mean turnaround for biopsy results in Saint Lucia was three times longer than overseas (p = 0.0013). Approximately half of survivors commenced treatment more than one month following diagnosis (median of 32 days, IQR 19-86 days), and 56% of survivors traveled out-of-country for treatment. Most survivors (60%) paid for care with family/friends support, followed by savings and medical insurance (38% each). In conclusion, cancer survivors in Saint Lucia are faced with complex circumstances, including access-to-care and health consequences. This study can guide future research, and possibly guide practice improvements in the near term.
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Supervivientes de Cáncer , Neoplasias , Atención a la Salud , Femenino , Humanos , Islas , Masculino , Neoplasias/terapia , Proyectos Piloto , Santa LuciaRESUMEN
Male breast cancer (MBC) is now considered molecularly different from female breast cancer (FBC). Evidence from studies indicates that common genetic and epigenetic features of FBC are not shared with those diagnosed in men. Genetic predisposition is likely to play a significant role in the tumorigenesis of this rare disease. Inherited germline variants in BRCA1 and BRCA2 account for around 2% and 10% of MBC cases, respectively, and the lifetime risk of breast cancer for men harboring BRCA1 and BRCA2 mutations is 1.2% and 6.8%. As for FBC, pathogenic mutations in other breast cancer genes have also been recently associated with an increased risk of MBC, such as PALB2 and CHEK2 mutations. However, while multigene germline panels have been extensively performed for BC female patients, the rarity of MBC has resulted in limited data to allow the understanding of the magnitude of risk and the contribution of recently identified moderate penetrance genes of FBC for MBC predisposition. This review gathers available data about the germline genetic landscape of men affected by breast cancer, estimated risk associated with these genetic variants, and current guidelines for clinical management.
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Infectious diseases and the rapid development of pathogens resistant to conventional drugs are a serious global public health problem, which motivates the search for new pharmacological agents. In this context, cationic peptides without disulfide bridges from different species of scorpion venom have been the target of scientific studies due to their multifunctional activities. Stigmurin is a linear peptide composed of 17 amino acid residues (Phe-Phe-Ser-Leu-Ile-Pro-Ser-Leu-Val-Gly-Gly-Leu-Ile-Ser-Ala-Phe-Lys-NH2), which is present in the venom gland of the scorpion Tityus stigmurus. Here we present investigations of the in vitro antioxidant action of Stigmurin together with the in vivo antibacterial and healing activity of this peptide in a wound infection model induced by Staphylococcus aureus. In addition, we have reports for the first time of the three-dimensional structure determined by NMR spectroscopy of a peptide without disulfide bridges present in scorpion venom from the Tityus genus. Stigmurin showed hydroxyl radical scavenging above 70 % at 10 µM and antibiotic action in the skin wound, reducing the number of viable microorganisms by 67.2 % on the 7 day after infection. Stigmurin (1 µg / µL) increased the retraction rate of the lesion, with wound area reduction of 43 % on the second day after skin injury, which indicates its ability to induce tissue repair. Stigmurin in trifluoroethanol:water exhibited a random conformation at the N-terminus region (Phe1 to Pro6), with a helical structure from Ser7 to Phe16. This structural information, allied with the multifunctional activity of Stigmurin, makes it an attractive candidate for the design of novel therapeutic agents.
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Péptidos Catiónicos Antimicrobianos/farmacología , Venenos de Escorpión/genética , Staphylococcus aureus/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Conformación Proteica , Venenos de Escorpión/química , Escorpiones/química , Staphylococcus aureus/patogenicidad , Infección de Heridas/microbiologíaRESUMEN
The relative benefit of bevacizumab in ovarian cancer (OC) patients is greater the more the disease becomes platinum-resistant. Among other mechanisms of action, antiangiogenic agents may induce homologous recombination deficiency. Cyclin E1 (CCNE1) overexpression is a proposed marker of platinum resistance and is mutually exclusive with deficiency in homologous recombination. In this study, we evaluated the predictive value of CCNE1 expression with regard to the efficacy of bevacizumab. We retrospectively evaluated data from patients with platinum-sensitive recurrent OC who were treated with chemotherapy (CT) plus bevacizumab (Bev group) or CT alone (CT group) at a tertiary cancer centre from 2005 to 2017. The two groups were paired according to histology, platinum-free interval (PFI) and number of previous treatment lines. Progression-free survival (PFS) was compared between groups by log rank test and Cox regression. A total of 124 patients were included, with 62 in each group. The groups were well balanced regarding histology, PFI and number of previous treatment lines. Median PFS (mPFS) was 19.5 months for the Bev group versus 16.0 months for CT group (p = 0.150). By multivariate analysis, the HR for PFS was 2.25 (95% CI: 1.10-4.60) for CCNE1 overexpression. The benefit of bevacizumab was larger in the subgroups of patients with PFI 6-12 months (mPFS 18.6 versus 10.4 months, p = 0.002) and CCNE1 overexpression (mPFS 16.3 versus 7.0 months, p = 0.010). In conclusion, CCNE1 overexpression and PFI may suggest which patients will receive the greatest benefit from bevacizumab. These data, if confirmed by other studies, could help better select patients for antiangiogenic therapy.
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Primary mucosal malignant melanomas of the gastrointestinal tract are rare tumors associated to poor prognosis. Primary duodenal involvement by pigmented lesions is even more uncommon, and only a few reports exist in the literature. We report the case of a patient with large primary duodenal melanoma that presented with upper intestinal obstruction and bleeding that was submitted to urgent pancreaticoduodenectomy followed by adjuvant systemic therapy with an oral alkylating agent (temozolomide) plus intravenous cisplatin. The patient presents no signs of recurrence 3 years after the surgery. We consider that radical surgical resection followed by systemic therapy is a safe and effective treatment strategy option for primary mucosal gastrointestinal melanomas.
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Melanoma , Recurrencia Local de Neoplasia , Terapia Combinada , Humanos , Melanoma/tratamiento farmacológico , Melanoma/cirugía , Pancreatectomía , PancreaticoduodenectomíaRESUMEN
BRCA1 and BRCA2 are major breast cancer susceptibility genes whose pathogenic variants are associated with a significant increase in the risk of breast and ovarian cancers. Current genetic screening is generally limited to BRCA1/2 exons and intron/exon boundaries. Most identified pathogenic variants cause the partial or complete loss of function of the protein. However, it is becoming increasingly clear that variants in these regions only account for a small proportion of cancer risk. The role of variants in non-coding regions beyond splice donor and acceptor sites, including those that have no qualitative effect on the protein, has not been thoroughly investigated. The key transcriptional regulatory elements of BRCA1 and BRCA2 are housed in gene promoters, untranslated regions, introns, and long-range elements. Within these sequences, germline and somatic variants have been described, but the clinical significance of the majority is currently unknown and it remains a significant clinical challenge. This review summarizes the available data on the impact of variants on non-coding regions of BRCA1/2 genes and their role on breast and ovarian cancer predisposition.
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The article presents a review of approaches and methodologies in the evaluation of STD/AIDS prevention programs, searching for theoretical and methodological support for the institutionalization of evaluation and decision-making. The review included the MEDLINE, SciELO, and ISI Web of Science databases and other sources like textbooks and congress abstracts from 1990 to 2005, with the key words: "evaluation", "programs", "prevention", "STD/AIDS", and similar terms. The papers showed a predominance of quantitative outcome or impact evaluative studies with an experimental or quasi-experimental design. The main use of evaluation is accountability, although knowledge output and program improvement were also identified in the studies. Only a few evaluative studies contemplate process evaluation and its relationship to the contexts. The review aimed to contribute to the debate on STD/AIDS, which requires more effective, consistent, and sustainable decisions in the field of prevention.
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Evaluación de Programas y Proyectos de Salud/métodos , Enfermedades de Transmisión Sexual/prevención & control , Síndrome de Inmunodeficiencia Adquirida/prevención & control , HumanosRESUMEN
BACKGROUND Hyperammonemic encephalopathy is a potentially fatal condition that may progress to irreversible neuronal damage and is usually associated with liver failure or portosystemic shunting. However, other less common conditions can lead to hyperammonemia in adults, such as fibrolamellar hepatocellular carcinoma. Clinical awareness of hyperammonemic encephalopathy in patients with normal liver function is paramount to timely diagnosis, but understanding the underlying physiopathology is decisive to initiate adequate treatment for complete recovery. CASE REPORT A 31-year-old male with fibrolamellar carcinoma and peritoneal carcinomatosis presented with rapid onset hyperammonemic encephalopathy. Despite usual treatment for hepatic encephalopathy, his hyperammonemia was aggravated. A physiopathological pathway to encephalopathy resulting from hepatocellular dysfunction or portosystemic shunting was suspected and proper treatment was initiated, which resulted in complete remission of encephalopathy. Thus, we propose there is a physiopathology path to hyperammonemic encephalopathy in non-cirrhotic patients with fibrolamellar carcinoma independent of ornithine transcarbamylase (OTC) mutation. An ornithine metabolism imbalance resulting from overexpression of Aurora Kinase A as a result of a single, recurrent heterozygous deletion on chromosome 19, common to all fibrolamellar carcinomas, can lead to a c-Myc and ornithine decarboxylase overexpression that results in ornithine transcarboxylase dysfunction with urea cycle disorder and subsequent hyperammonemia. CONCLUSIONS The identification of a physiopathological pathway allowed adequate medical treatment and full patient recovery from severe hyperammonemic encephalopathy.