RESUMO
Anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy is an increasingly crucial in cancer treatment. To date, the Federal Drug Administration (FDA) has approved four PD-L1 immunohistochemistry (IHC) staining protocols, commercially available in the form of "kits", facilitating testing for PD-L1 expression. These kits comprise four PD-L1 antibodies on two separate IHC platforms, each utilizing distinct, non-interchangeable scoring systems. Several factors, including tumor heterogeneity and the size of the tissue specimens assessed, can lead to PD-L1 status misclassification, potentially hindering the initiation of therapy. Therefore, the development of more accurate predictive biomarkers to distinguish between responders and non-responders prior to anti-PD-1/PD-L1 therapy warrants further research. Achieving this goal necessitates refining sampling criteria, enhancing current methods of PD-L1 detection, and deepening our understanding of the impact of additional biomarkers. In this article, we review potential solutions to improve the predictive accuracy of PD-L1 assessment in order to more precisely anticipate patients' responses to anti-PD-1/PD-L1 therapy, monitor disease progression and predict clinical outcomes.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/metabolismo , Imuno-Histoquímica , Antígeno B7-H1 , Biomarcadores Tumorais/metabolismo , ImunoterapiaRESUMO
We investigated the transformation of four pharmaceuticals (Diclofenac, Naproxen, Ibuprofen and Carbamazepine) in a moving bed biofilm reactor subjected to different COD/N ratios in four experimental phases. The shift from medium to high range COD/N ratio (i.e., 5:1 to 100:1) intensified the competition between heterotrophs and nitrifying communities, leading to a transition from co-existence of heterotrophic and autotrophic conditions with high COD removal and nitrification rate in phase I to dominant heterotrophic conditions in phase II. At lower range COD/N ratios (i.e., 1:2 and 1:8) in phase III and IV, autotrophic conditions prevailed, resulting in increased nitrification rates and high abundance of amoA gene in the biofilm. Such shifts in the operating condition were accompanied by notable changes in the biofilm concentrations, composition and abundance of microbial populations as well as biodiversity in the biofilms, which collectively affected the degradation rates of the pharmaceuticals. We observed higher kinetic rates per unit of biofilm concentration under autotrophic conditions compared to heterotrophic conditions for all compounds except Naproxen, indicating the importance of nitrification in the transformation of such compounds. The results also revealed a positive relationship between biodiversity and biomass-normalized kinetic rates of most compounds.
Assuntos
Biodiversidade , Naproxeno , Biotransformação , Biofilmes , Preparações FarmacêuticasRESUMO
In certain instances, patients who underwent endoscopic laser excision (ELE) for biopsy-proven early glottic carcinoma do not show any evidence of carcinomatous cells on histopathologic analysis. Our study aims to determine the incidence of this phenomenon. A retrospective analysis of patients with biopsy-proven early glottic squamous cell carcinoma who underwent ELE was conducted. 121 patients with a mean age of 68.2 ± 10.7 were included in this study. Initial biopsy showed carcinoma in situ in 38 patients, (31.4%), T1a in 41 patients (33.9%), and T1b in 42 patients (34.7%). Following ELE, a pathologically negative excision was seen in 26 patients (21.5%). Disease recurrence occurred in 3 patients who had a pathologically negative excision (11.5%). Following repeat ELE, all patients remained disease free. A significant number of early glottic carcinoma present with small volume disease which may be eradicated with diagnostic biopsy alone.
RESUMO
Introduction: Early laryngeal carcinomas may be treated by transoral laser microsurgery (TLM) or external beam radiotherapy. We review our experience of surgical treatment of laryngeal pre-malignant and malignant lesions over the past 15 years in a high-volume head neck unit. Methods: A review of a prospective patient database of patients with laryngeal SCC, who were treated with CO2 TLM between 2004 and 2019 was carried out. Results: 83 patients with a mean age of 67.7 (SD: 10.6) years underwent primary curative TLM for T1a/b SCC. 5-year overall survival was 93.2% (95%CI 86.9-100%), disease free survival was 86.0% (95%CI 78.1-94.6%), locoregional control was 91.2% (95%CI: 85.1-97.7%) and larynx preservation rate of 95.1% at 5 years. Conclusion: TLM is an excellent treatment modality for T1 early glottic SCC, with excellent locoregional control and disease-free survival. It is minimally invasive, outpatient-based, and cost-effective procedure preserving upper aerodigestive tract dysfunction for all activities of daily living.
RESUMO
Background: Cisplatin is among the most effective antineoplastic agents and has revolutionized the treatment of many cancer diseases. However, one of its serious side effects is a progressive and irreversible hearing loss, occurring in both adults and children. For the development of otoprotective therapies that prevent this side effect, cisplatin-induced hearing loss animal models are indispensable. Due to the high toxicity of cisplatin, the establishment of such animal models is a difficult and time-consuming task. Here we introduce the detailed protocol of a sophisticated guinea pig model with a sufficient and permanent hearing loss induced by cisplatin. This manuscript is intended to provide guidance in the development of future cisplatin guinea pig models which may reduce the mortality rate of the animals and help to gain more reproducible results. Methods: Pigmented and unpigmented guineapigs were treated with an intravenous single application of 8 mg/kg cisplatin under general anesthesia. An extensive and long-term intensive care protocol consisting of scheduled application of fluids, antiemetics, analgesics, glucose and supportive feeding among others, was used to ensure wellbeing of the animals. Hearing tests were performed prior to and 5 days after cisplatin application. Animals were then euthanized. Results: The ABR audiometry 5 days after cisplatin application revealed a hearing threshold ranging from 70 dB to 90 dB in the frequencies from 1 kHz to 32 kHz respectively.All animals presented a good health condition despite the treatment with cisplatin. Discussion: The introduced care protocol in this manuscript is intended to serve as a guidance for the establishment of a stable guinea pig model for short- and long-term investigation regarding the inner ear and its protection in the frame work of cisplatin-induced damage.
RESUMO
BACKGROUND: Diverticular disease of the colon occurs commonly in developed countries. Immunosuppressed patients are thought to be more at risk of developing acute diverticulitis, worse disease, and higher complications secondary to therapy. This study aimed to assess outcomes for immunosuppressed patients with acute diverticulitis. METHOD: A retrospective single-centre review was conducted of all patients presenting with acute diverticulitis at a major tertiary Australian hospital from 2006 to 2018. RESULT: A total of 751 patients, comprising of 46 immunosuppressed patients, were included. Immunosuppressed patients were found to be older (62.25 versus 55.96, p = 0.016), have more comorbidities (median Charlson Index 3 versus 1, P < 0.001), and undergo more operative management (13.3% versus 5.1%, P = 0.020). Immunosuppressed patients with paracolic/pelvic abscesses (Modified Hinchey 1b/2) were more likely to undergo surgery (56% versus 24%, P = 0.046), while in patients with uncomplicated diverticulitis, there was no difference in immunosuppressed patients undergoing surgery (6.1% versus 5.1% P = 0.815). Immunosuppressed patients were more likely to have Grade III-IV Clavien-Dindo complication (P < 0.001). CONCLUSION: Immunosuppressed patients with uncomplicated diverticulitis can be treated safely with non-operative management. Immunosuppressed patients were more likely to have operative management for Hinchey 1b/II and more likely to have grade III/IV complications.
Assuntos
Doença Diverticular do Colo , Diverticulite , Humanos , Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/cirurgia , Estudos Retrospectivos , Austrália/epidemiologia , Recidiva Local de Neoplasia , Diverticulite/cirurgia , Doença AgudaRESUMO
To shed some light on glycotargeting as a potential strategy for nasal drug delivery, a reliable preparation method for human nasal mucosa samples and a tool to investigate the carbohydrate building blocks of the glycocalyx of the respiratory epithelium are required. Applying a simple experimental setup in a 96-well plate format together with a panel of six fluorescein-labeled lectins with different carbohydrate specificities allowed for the detection and quantification of accessible carbohydrates in the mucosa. As confirmed by binding experiments at 4 °C, both quantitatively by fluorimetry and qualitatively by microscopy, the binding of wheat germ agglutinin exceeded that of the others by 150% on average, indicating a high content of N-acetyl-D-glucosamine and sialic acid. Providing energy by raising the temperature to 37 °C revealed uptake of the carbohydrate-bound lectin into the cell. Moreover, repeated washing steps during the assay gave a slight hint as to the influence of mucus renewal on bioadhesive drug delivery. All in all, the experimental setup reported here for the first time is not only a suitable approach to estimating the basics and potential of nasal lectin-mediated drug delivery but also meets the needs for answering a broad variety of scientific questions involving the use of ex vivo tissue samples.
RESUMO
Primary neuroendocrine tumor (NET) of bladder is rare. It has four subtypes, and large cell neuroendocrine carcinoma (LCNEC) is the rarest. LCNEC affects mostly men over 60. Most common symptom is gross hematuria. It has no specific treatment. Metastasis is common and once occurred, average survival would be less than three months. Herein we present diagnostic and therapeutic management of a 65-year-old female with LCNEC of bladder and concurrent high-grade urothelial carcinoma. Despite developing early liver metastasis, she achieved a one-year tumor-free survival.
RESUMO
OBJECTIVES: To measure the unit-level variation in Acute Kidney Injury (AKI) incidence post-thoracic surgery over a contemporary 1-year period. Secondary aims include examining the associations with sex, age group, operation type, length of stay and mortality. DESIGN: A multicentre, observational, retrospective study in thoracic surgery. SETTING: 17 of 35 Society for Cardiothoracic Surgery of Great Britain and Ireland (SCTS) units participated. The student wing, known as SCTS STUDENTS, supported data collection. PARTICIPANTS: Overall, 15 229 patients were collected of which 15 154 were included for analysis after exclusions. All patients (age≥18 years) undergoing any thoracic surgery from 1 April 2016 to 31 March 2017 were included. For analysis, we excluded patients with preoperative end-stage renal failure and those with incomplete data. MAIN OUTCOME MEASURES: The primary outcome is the incidence of AKI within 7 days of the procedure or discharge date if earlier. Secondary outcomes include assessing associations with patient demographics (age, sex), type of procedure (open and minimally invasive), length of stay and mortality. RESULTS: Out of 15 154 patients AKI was diagnosed in 1090 patients (7.2%) within 7 days of surgery with AKI stage 1 (4.8%), stage 2 (1.7%) and stage 3 (0.7%). There was a statistically significant variation in AKI incidence between units from 3.1 to 16.1% (p<0.05). Significant differences between AKI and non-AKI were found in post-operative length of stay (7 vs 3 days, p<0.001), 30-day mortality (9 vs 1.6%, p<0.001), 90-day mortality (14.7 vs 4.4%, p<0.001) and 1-year mortality (23.1 vs 12.2 %, p<0.001). CONCLUSIONS: Following thoracic surgery, AKI incidence ranged from 3.1% to 16.1% between units (p<0.05) with associations between AKI and both length of stay and mortality. We propose AKI as a suitable comparative and absolute quality measure in thoracic surgery. Reducing rates of AKI may improve patient outcomes, length of stay and reduce costs.
Assuntos
Injúria Renal Aguda , Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adolescente , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Procedimentos Cirúrgicos Torácicos/efeitos adversosRESUMO
AIM: To present an institution's experience and survival outcomes for patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) and perineural spread (PNS). METHOD: Retrospective study of patients with HNcSCC and PNS treated between January 2010 and August 2020 from the Sydney Head and Neck Cancer Institute database, Sydney, Australia; a high-volume, tertiary, academic head and neck centre. Patient demographics, primary site, involved cranial nerves, treatment modality, loco-regional failure and survival data were obtained. RESULTS: Forty-five patients were identified, of which 32 patients were male (71%). Mean age at diagnosis was 68.7 years (range 43-90). Median follow-up was 16.1 months (range 1-107). The trigeminal nerve was most frequently involved (n = 30, 66.6%) followed by facial nerve (n = 13, 28.9%). Most patients underwent surgery followed by radiotherapy (n = 33, 73%) and eight received definitive radiotherapy. The median overall survival (OS) was 4.5 years (95% CI 3.71-5.38), median disease-specific survival 5.1 years (95% CI 4.21-5.97) and median disease-free survival (DFS) was 1.7 years (95% CI 1.11-2.22). The estimated 5-year OS and DFS were 45% and 25%, respectively. Patients treated with surgery and adjuvant radiotherapy with a clear proximal nerve margin had favourable DFS (P = 0.035) and trended towards better OS (P = 0.134) compared with patients with an involved nerve margin. Patients treated surgically with involved proximal nerve margins had similar outcomes compared with patients with treated definitive radiotherapy (HR 0.80, 95% CI 0.29-2.22, P = 0.664). CONCLUSION: The likelihood of achieving a clear proximal nerve margin should be a strong consideration in the selection of appropriate patients for primary surgery.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Cutâneas , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
PURPOSE: Endoscopic biopsy is recommended for diagnosis of nasopharyngeal carcinoma (NPC). A proportion of lesions are hidden from endoscopic view but detected with magnetic resonance imaging (MRI). This systematic review and meta-analysis investigated the diagnostic performance of MRI for detection of NPC. METHODS: An electronic search of twelve databases and registries was performed. Studies were included if they compared the diagnostic accuracy of MRI to a reference standard (histopathology) in patients suspected of having NPC. The primary outcome was accuracy for detection of NPC. Random-effects models were used to pool outcomes for sensitivity, specificity, and positive and negative likelihood ratio (LR). Bias and applicability were assessed using the modified QUADAS-2 tool. RESULTS: Nine studies were included involving 1736 patients of whom 337 were diagnosed with NPC. MRI demonstrated a pooled sensitivity of 98.1% (95% CI 95.2-99.3%), specificity of 91.7% (95% CI 88.3-94.2%), negative LR of 0.02 (95% CI 0.01-0.05), and positive LR of 11.9 (95% CI 8.35-16.81) for detection of NPC. Most studies were performed in regions where NPC is endemic, and there was a risk of selection bias due to inclusion of retrospective studies and one case-control study. There was limited reporting of study randomization strategy. CONCLUSION: This study demonstrates that MRI has a high pooled sensitivity, specificity, and negative predictive value for detection of NPC. MRI may be useful for lesion detection prior to endoscopic biopsy and aid the decision to avoid biopsy in patients with a low post-test probability of disease.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias Nasofaríngeas , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Perinueral invasion (PNI) is recognized as an independent adverse prognostic factor associated with shorter disease free and disease specific survival in a range of malignancies. However, not all histologically detected PNI demonstrate aggressive biologic behaviour. Herein, we systematically review the literature to identify neurotrophic biomarkers that may potentially be used to predict the biologic potential of PNI. METHOD: A systematic review was conducted based on PRISMA guidelines utilising the search terms 'PNI', 'DNA' and 'RNA' analysis in select malignancies following registry of the search strategy on PROSPERO. The biologic role of the molecular markers identified through the literature review was examined using publicly available databases, such as Gene Cards and Kyoto Encyclopedia of Genes and Genomes (KEGG) with a focused literature review of the identified pathways. RESULTS: The systematic search identified 256 studies, of which 78 studies were suitable for data extraction. A variety of methodologies including immunohistochemistry, immunoblotting, nucleic acid sequencing, Luciferase assays and CRISPR techniques have been undertaken to evaluate the biologic potential of PNI. The studies evaluated 136 unique molecules. Of these, only 15 molecules were investigated through multiple studies with concordant results or had robust functional analyses. Three pathways were identified as playing a role in PNI, namely; the epithelial-mesenchymal transition pathway, neurotrophic pathway and Notch pathway. DISCUSSION: Our understanding of the complex and reciprocal interaction between tumour and nerve cells that drives PNI is still evolving. The knowledge gaps can largely be attributed to publication bias, lack of availability of high-quality patient derived tissues and limitations of currently available technology. This review summarises the current knowledge regarding development and progression of PNI that can be harnessed for prognostication and treatment. This review also summarises the lacunae in our understanding of the pathogenesis of PNI thus identifying avenues for future studies.
Assuntos
Produtos Biológicos , Transição Epitelial-Mesenquimal , Intervalo Livre de Doença , Humanos , Invasividade Neoplásica/patologia , Nervos Periféricos/patologia , PrognósticoRESUMO
Primary malignant melanoma (PMM) of the urinary bladder is a rare disease. Symptoms include gross hematuria and irritative LUTS. The diagnosis is made with cystoscopy and TURBT. Treatment options include TURBT and adjuvant therapies. We present a 61-year-old female who was referred with persistent irritative LUTS without gross or microscopic hematuria. After undergoing cystoscopy, TURBT, and extensive workup, she was diagnosed with PMM of the urinary bladder. Due to her past medical history, recurrent PMM of the urinary bladder was the final diagnosis. She refused to receive further treatment or refer for follow-up.
RESUMO
Currently, multiple myeloma is not yet considered a curable disease. Despite the recent advances in therapy, the average patient lifespan is still unsatisfactory. Recently, CDK9 inhibitors emerged as a suitable agent to overcome resistance and prolong survival in patients with poor diagnoses. Downregulation of c-MYC, XIAP, Mcl-1 and restoration of p53 tumor-suppressive functions seems to play a key role in achieving clinical response. The applicability of the first generation of CDK9 inhibitors was limited due to relatively high toxicity, but the introduction of novel, highly selective drugs, seems to reduce the effects of off-target inhibition. CDK9 inhibitors were able to induce dose-dependent cytotoxicity in Doxorubicin-resistant, Lenalidomide-resistant and Bortezomib-resistant cell lines. They seem to be effective in cell lines with unfavorable prognostic factors, such as p53 deletion, t(4; 14) and t(14; 16). In preclinical trials, the application of CDK9 inhibitors led to tumor cells apoptosis, tumor growth inhibition and tumor mass reduction. Synergistic effects between CDK9 inhibitors and either Venetoclax, Bortezomib, Lenalidomide or Erlotinib have been proven and are awaiting verification in clinical trials. Although conclusions should be drawn with due care, obtained reports suggest that including CDK9 inhibitors into the current drug regimen may turn out to be beneficial, especially in poor prognosis patients.
Assuntos
Antineoplásicos/farmacologia , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Mieloma Múltiplo/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Terapia de Alvo MolecularRESUMO
Desmoplasia is crucial for the development, progression and treatment of immune-resistant malignancies. Targeting desmoplasia-related metabolic pathways appears to be an interesting approach to expand our stock of disposable anti-tumor agents. CXCL12/CXCR4 axis inhibition reduces fibrosis, alleviates immunosuppression and significantly enhances the efficacy of PD-1 immunotherapy. CD40L substitute therapy may increase the activity of T-cells, downregulate CD40+, prolong patients' survival and prevent cancer progression. Although FAPα antagonists used in preclinical models did not lead to permanent cure, an alleviation of immune-resistance, modification of desmoplasia and a decrease in angiogenesis were observed. Targeting DDR2 may enhance the effect of anti-PD-1 treatment in multiple neoplasm cell lines and has the ability to overcome the adaptation to BRAF-targeted therapy in melanoma. Reprogramming desmoplasia could potentially cooperate not only with present treatment, but also other potential therapeutic targets. We present the most promising metabolic pathways related to desmoplasia and discuss the emerging strategies to improve the efficacy of immunotherapy.
Assuntos
Imunoterapia , Melanoma , Linhagem Celular Tumoral , Humanos , Terapia de Alvo Molecular , Linfócitos TRESUMO
Perineural invasion (PNI) is frequently associated with aggressive clinical behaviour in head and neck cutaneous squamous cell carcinoma (HNcSCC) leading to local recurrence and treatment failure. This study evaluates the gene expression profiles of HNcSCC with PNI using a differential expression analysis approach and constructs a tailored gene panel for sensitivity and specificity analysis. 45 cases of HNcSCC were stratified into three groups (Extensive, Focal and Non PNI) based on predefined clinicopathological criteria. Here we show HNcSCC with extensive PNI demonstrates significant up- and down-regulation of 144 genes associated with extracellular matrix interactions, epithelial to mesenchymal transition, cell adhesion, cellular motility, angiogenesis, and cellular differentiation. Gene expression of focal and non PNI cohorts were indistinguishable and were combined for further analyses. There is clinicopathological correlation between gene expression analysis findings and disease behaviour and a tailored panel of 10 genes was able to identify extensive PNI with 96% sensitivity and 95% specificity.
Assuntos
Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Idoso , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Invasividade Neoplásica/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Nervos Periféricos/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Hepatocellular carcinoma (HCC) is the fourth most common cause of death among cancers. The poor prognosis of HCC might be caused by a population of cancer stem cells (CSC). CSC have similar characteristics to normal stem cells and are responsible for cancer recurrence, chemoresistance, radioresistance and metastasis. Liver cancer stem cells (LCSC) are identified via specific surface markers, such as CD44, CD90, CD133, and EpCAM (CD326). Recent studies suggested a complex interaction between mentioned LCSC markers and clinical features of HCC. A high expression of CSC is correlated with a negative prognostic factor after surgical resection of HCC and is connected with more aggressive tumor behavior. Moreover, LCSC might be responsible for increasing resistance to sorafenib, a kinase inhibitor drug. A reduction in the LCSC population may be crucial to successful advanced HCC therapy.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia , Células-Tronco Neoplásicas , PrognósticoRESUMO
BACKGROUND/AIM: Immunohistochemistry (IHC) enables visualisation of the distribution of specific proteins, the differentiation of benign and malignant tumours, and the site and origin of a primary tumour. Surgical pathologists commonly examine tumours with extensive necrosis or non-viable tissue that may affect an accurate diagnosis. MATERIALS AND METHODS: We investigated the sensitivity and specificity of IHC on necrotic samples derived from adenocarcinoma, squamous cell carcinoma (SCC) and melanoma using different markers. RESULTS: Analysis of necrosis within tumours revealed 88% sensitivity and 56% specificity for melanoma, 95% and 92% for CK5/6, 95% and 83% for CK20, 37% and 95% for p63, 69% and 97% for Melan A, 88% and 92% for SOX-10, 98% and 56% for CKAE/AE3 and 75% specificity for CK7. CONCLUSION: Antibodies should be considered reliable markers for demonstrating the epithelial nature of a suspected tumour. Immunohistochemistry of necrotic tissues may provide clinically useful information.
Assuntos
Imuno-Histoquímica , Necrose/patologia , Neoplasias/diagnóstico , Biomarcadores Tumorais , Diagnóstico Diferencial , Humanos , Sensibilidade e EspecificidadeRESUMO
We investigated the performance of a lab-scale moving bed biofilm reactor (MBBR) with respect to general bioconversion processes and biotransformation of two commonly used organophosphorus pesticides, Chlorpyrifos (CHL) and Malathion (MAL). The reactor was operated for 300 days under different organic loads by changing hydraulic retention time (HRT). The decrease in organic load resulted in the formation of a thinner biofilm and the growth of more biomass in the bulk, which greatly shifted bioconversion processes. The low organic loading supported more nitrification in the reactor, but an opposite trend was observed for denitrification, which was enhanced at higher organic loading where the formation of anoxic zones in the thick biofilm was favored. 70% and 55% removal corresponding to 210 and 165 µg/m2/d occurred for MAL and CHL, respectively, at an HRT of 3 h and progressively increased with higher HRTs. Phylogenetic analysis revealed a shift in composition and abundance of taxa throughout the reactor operation where lower loading rate supported the growth of a more diverse and evenly distributed community. The analysis also highlighted the dominance of heterotrophic communities such as Flavobacterium and Acinetobacter johnsonii, which could be involved in the biotransformation of CHL and MAL through co-metabolism.