scholarly journals Clinical Proteomics of Biofluids in Haematological Malignancies

2021 ◽  
Vol 22 (15) ◽  
pp. 8021
Author(s):  
Katie Dunphy ◽  
Kelly O’Mahoney ◽  
Paul Dowling ◽  
Peter O’Gorman ◽  
Despina Bazou
Keyword(s):  
Minimally Invasive ◽  
Residual Disease ◽  
Predictive Biomarkers ◽  
Clinical Proteomics ◽  
Haematological Malignancies ◽  
Protein Biomarkers ◽  
Diagnosis And Prognosis ◽  
Promising Source ◽  
Haematologic Malignancies ◽  
Made In

Since the emergence of high-throughput proteomic techniques and advances in clinical technologies, there has been a steady rise in the number of cancer-associated diagnostic, prognostic, and predictive biomarkers being identified and translated into clinical use. The characterisation of biofluids has become a core objective for many proteomic researchers in order to detect disease-associated protein biomarkers in a minimally invasive manner. The proteomes of biofluids, including serum, saliva, cerebrospinal fluid, and urine, are highly dynamic with protein abundance fluctuating depending on the physiological and/or pathophysiological context. Improvements in mass-spectrometric technologies have facilitated the in-depth characterisation of biofluid proteomes which are now considered hosts of a wide array of clinically relevant biomarkers. Promising efforts are being made in the field of biomarker diagnostics for haematologic malignancies. Several serum and urine-based biomarkers such as free light chains, β-microglobulin, and lactate dehydrogenase are quantified as part of the clinical assessment of haematological malignancies. However, novel, minimally invasive proteomic markers are required to aid diagnosis and prognosis and to monitor therapeutic response and minimal residual disease. This review focuses on biofluids as a promising source of proteomic biomarkers in haematologic malignancies and a key component of future diagnostic, prognostic, and disease-monitoring applications.

Morphologic differences between abdominal and inguinal testes in stallions

1987 ◽  
Vol 45 ◽  
pp. 820-821
Author(s):  
F. Al-Bagdadi ◽  
D. Hoyt ◽  
P. Karns ◽  
G. Martin ◽  
M. Memon ◽  
...  
Keyword(s):  
Carcinoma Cells ◽  
Genital System ◽  
Diagnosis And Prognosis ◽  
Male Genital System ◽  
Morphological Differences ◽  
Hormone Imbalance ◽  
Made In ◽  
Male Genital

The most frequently occuring abnormality of the male genital system in mammals is the failure of one or both testes to descend into the scrotum. The reasons for abdominal or inguinal retention of testes could be anatomic malformation, faulty development or hormone imbalance.Cryptorchidism has been associated with either greatly reduced or absent spermatogenesis (Kaueakami et al, 1984), and being a source of neoplasia. According to Stick (1980), germinal carcinoma cells have been believed to be the cause of teratomas in equine cryptorchid testicles. Neoplasia has been reported in descended testes of unilateral cryptorchid patients (Martin et al, 1981).No distinction has been made in relating the problem of cryptorchid testes to inguinal or abdominal retention. The purpose of this study is to record the morphological differences between inguinal and abdominal cryptorchid testes as an aid in diagnosis and prognosis.

scholarly journals ctDNA-Based Liquid Biopsy of Cerebrospinal Fluid in Brain Cancer

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1989
Author(s):  
Laura Escudero ◽  
Francisco Martínez-Ricarte ◽  
Joan Seoane
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Cancer ◽  
Liquid Biopsy ◽  
Therapeutic Strategy ◽  
Residual Disease ◽  
Imaging Techniques ◽  
Prognostic Information ◽  
Tumour Heterogeneity ◽  
Diagnosis And Prognosis ◽  
Cns Malignancies

The correct characterisation of central nervous system (CNS) malignancies is crucial for accurate diagnosis and prognosis and also the identification of actionable genomic alterations that can guide the therapeutic strategy. Surgical biopsies are performed to characterise the tumour; however, these procedures are invasive and are not always feasible for all patients. Moreover, they only provide a static snapshot and can miss tumour heterogeneity. Currently, monitoring of CNS cancer is performed by conventional imaging techniques and, in some cases, cytology analysis of the cerebrospinal fluid (CSF); however, these techniques have limited sensitivity. To overcome these limitations, a liquid biopsy of the CSF can be used to obtain information about the tumour in a less invasive manner. The CSF is a source of cell-free circulating tumour DNA (ctDNA), and the analysis of this biomarker can characterise and monitor brain cancer. Recent studies have shown that ctDNA is more abundant in the CSF than plasma for CNS malignancies and that it can be sequenced to reveal tumour heterogeneity and provide diagnostic and prognostic information. Furthermore, analysis of longitudinal samples can aid patient monitoring by detecting residual disease or even tracking tumour evolution at relapse and, therefore, tailoring the therapeutic strategy. In this review, we provide an overview of the potential clinical applications of the analysis of CSF ctDNA and the challenges that need to be overcome in order to translate research findings into a tool for clinical practice.

scholarly journals Methodology and Applications of Disease Biomarker Identification in Human Serum

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Ziad J. Sahab ◽  
Suzan M. Semaan ◽  
Qing-Xiang Amy Sang
Keyword(s):  
Human Serum ◽  
Protein Separation ◽  
High Sensitivity ◽  
Disease Diagnosis ◽  
Plasma Lipoproteins ◽  
Great Promise ◽  
Protein Biomarkers ◽  
Serum Samples ◽  
Disease Biomarkers ◽  
Diagnosis And Prognosis

Biomarkers are biomolecules that serve as indicators of biological and pathological processes, or physiological and pharmacological responses to a drug treatment. Because of the high abundance of albumin and heterogeneity of plasma lipoproteins and glycoproteins, biomarkers are difficult to identify in human serum. Due to the clinical significance the identification of disease biomarkers in serum holds great promise for personalized medicine, especially for disease diagnosis and prognosis. This review summarizes some common and emerging proteomics techniques utilized in the separation of serum samples and identification of disease signatures. The practical application of each protein separation or identification technique is analyzed using specific examples. Biomarkers of cancers of prostate, breast, ovary, and lung in human serum have been reviewed, as well as those of heart disease, arthritis, asthma, and cystic fibrosis. Despite the advancement of technology few biomarkers have been approved by the Food and Drug Administration for disease diagnosis and prognosis due to the complexity of structure and function of protein biomarkers and lack of high sensitivity, specificity, and reproducibility for those putative biomarkers. The combination of different types of technologies and statistical analysis may provide more effective methods to identify and validate new disease biomarkers in blood.

Classifications of acute pancreatitis: to Atlanta and beyond

Open Medicine ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. 543-549
Author(s):  
Anna Pallisera ◽  
Farah Adel ◽  
Jose Ramia
Keyword(s):  
Acute Pancreatitis ◽  
Minimally Invasive ◽  
Surgical Management ◽  
Historical Review ◽  
Diagnostic Methods ◽  
Local Complications ◽  
Made In

AbstractUntil Atlanta Classification (AC) made in 1992, there was not any classification of acute pancreatitis (AP). Last twenty years AC let us compare results and papers. But the increasing understanding of the pathophysiology of AP, improvements in diagnostic methods and the development of minimally invasive tools for radiological, endoscopic and surgical management of local complications, several authors have called for the AC to be reviewed. Last months, two new classifications of AP have been published. We made a historical review of AC, the two new classifications and a comparison between them.

scholarly journals miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 276 ◽  
Author(s):  
Carmen Elena Condrat ◽  
Dana Claudia Thompson ◽  
Madalina Gabriela Barbu ◽  
Oana Larisa Bugnar ◽  
Andreea Boboc ◽  
...  
Keyword(s):  
High Specificity ◽  
Research Field ◽  
Therapeutic Interventions ◽  
Protein Levels ◽  
Diagnosis And Prognosis ◽  
Specificity And Sensitivity ◽  
Online Databases ◽  
Patient Profiles ◽  
Potential Use ◽  
Made In

MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.

Drug Development: Neoadjuvant Opportunities in Breast Cancer

2013 ◽  
pp. 73-79
Author(s):  
Priya Rastogi ◽  
Charles E. Geyer ◽  
Eleftherios P. Mamounas ◽  
Angela DeMichele
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cancer Biology ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Predictive Biomarkers ◽  
Preoperative Therapy ◽  
New Agents ◽  
Her2 Breast Cancer ◽  
Improved Outcomes

Preoperative therapy allows for a higher rate of breast conserving surgery and has been shown equivalent to adjuvant therapy. Preoperative therapy provides an opportunity to obtain insights into breast cancer biology and to accelerate the evaluation of new therapies. Clinical trials have shown that women who achieve a pathologic complete response (pCR) have substantially improved outcomes compared with those who do not achieve a pCR. The U.S. Food and Drug Administration (FDA) meta-analysis demonstrated that the association of pCR and long-term outcomes is greater in women with aggressive breast cancer subtypes. In patients with HER2+ breast cancer, the addition of trastuzumab to chemotherapy in the neoadjuvant setting has doubled pCR and correlated with improved outcomes. Clinical trials will evaluate tailoring the use of radiation therapy in patients who have received neoadjuvant therapy. Trials have established neoadjuvant endocrine therapy as a valid treatment and research option for ER-rich breast cancer. The neoadjuvant setting allows for evaluation of endocrine therapies in combination with newer targeted therapies in the appropriate patient populations. The neoadjuvant setting provides opportunity to accelerate the evaluation of new agents, improve pCR rates, and identify predictive biomarkers for response. This setting provides the opportunity for screening new agents in combination with chemotherapy while obtaining serial biopsies to understand biology of response and resistance. Although current standard therapies provide substantial benefits for patients with a pCR, patients with residual disease are at substantial risk for disease recurrence. New agents are being evaluated in patients with high-risk residual disease following standard treatment regimens.

scholarly journals Thymectomy in Myasthenia Gravis

2018 ◽  
Vol 2 (02) ◽  
pp. E124-E130
Author(s):  
Jens Rückert ◽  
Marc Swierzy ◽  
Siegfried Kohler ◽  
Andreas Meisel ◽  
Mahmoud Ismail
Keyword(s):  
Minimally Invasive ◽  
Myasthenia Gravis ◽  
Median Sternotomy ◽  
Surgical Techniques ◽  
Thymic Tissue ◽  
Unilateral Approach ◽  
Immunosuppressive Medication ◽  
Receptor Antibodies ◽  
Made In

AbstractIn recent years much progress has been made in the investigation of the pathophysiology, characterizing subgroups, and extension of multimodal treatment of myasthenia gravis (MG). This applies especially to the role of thymectomy (Thx). Thymectomy is always indicated for thymoma-associated myasthenia gravis. Furthermore, based on large cohort studies, during recent decades thymectomy has also become a central part of immune-modulating MG therapy in patients without thymoma. The lack of randomized studies, however, caused a certain persistent reluctance as to the significance of thymectomy. The current MGTX trial has shown the effectiveness of thymectomy. A significant improvement of myasthenic complaints and the reduction of immunosuppressive medication was primarily shown for acquired early-onset MG (EOMG) with complete resection of all thymic tissue. Because the MGTX study only included patients younger than 65 years with generalized MG and positive for acetylcholine-receptor antibodies, at present the significance of Thx for other relevant subgroups as juvenile MG, MG in older patients, ocular MG, as well as seronegative patients is under investigation. Even the prevailing opinion of no benefit of thymectomy for MuSk-positive patients probably needs reevaluation based on ambiguous findings. With respect to surgery, based on the exclusive performance of extended median sternotomy for MG in the MGTX, the value of thoracoscopic modifications for thymectomy as a minimally-invasive alternative is currently under evaluation. For clinical reasons further judgment regarding different minimally-invasive thymectomy techniques compared to the conventional open procedures in the form of randomized comparative studies would be required. Currently, however, an experience-based robotic-assisted thoracoscopic unilateral approach to thymectomy meets all requirements related to surgical, clinical-neurological and patient aspects. Ethical reasons, therefore, will lead to other strategies for comparison of different surgical techniques.

Tumor infiltrating lymphocytes (TIL) assessment in muscle invasive bladder cancer (MIBC) patients treated with cisplatin-based neoadjuvant chemotherapy (NAC) and surgery.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 547-547
Author(s):  
Nieves Martinez Chanza ◽  
Anis Hamid ◽  
Roberto Salgado ◽  
Thomas Gevaert ◽  
Marion Maetens ◽  
...  
Keyword(s):  
Residual Disease ◽  
Cohort Analysis ◽  
Predictive Biomarkers ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Kaplan Meier ◽  
Retrospective Cohort Analysis ◽  
Muscle Invasive ◽  
Infiltrating Lymphocytes ◽  
Free Rate

547 Background: Cisplatin-based NAC followed by surgery is the gold standard treatment of non-metastatic MIBC. However, predictive biomarkers have not been established yet. Here, we addressed the relevance of TILs for NAC response and prognosis in MIBC patients (pts). Methods: We conducted a single center, retrospective cohort analysis of consecutive MIBC pts treated with cisplatin-based NAC followed by surgery. Pts with pathological complete response (pCR; ypT0/isN0) were grouped as responders, pts with pathological residual disease as non responders. TIL stromal count were assessed pre- and post-NAC. Next Generation Sequencing of selected genes was performed on pre-NAC samples. We catalogued the 3-years(y) relapse free rate and 3-y overall survival rate (OS, Kaplan Meier) for the overall cohort and by subgroups. Results: Of the 25 pts who received cisplatin-gemcitabine NAC, a total of 14 (56%) pts achieved a pCR and 11 (44%) had residual disease. NAC was discontinued in 17 (65%) after completing treatment; and in 8 (32%) pts after 2 cycles due to toxicity. Median follow-up was 54.2 months(mos). At baseline, median TIL count was 60% in the overall cohort. Numerically higher TIL count was observed among responders (80%) compared to non-responders (50%) ( p=0.22). Median TIL count post-NAC in residual samples was 40%, not significantly different to matched pre-NAC samples ( p=0.93). Overall, 3-y relapse free rate was 74.7% (95%CI 51.7-87.9); 3-y OS rate was 79.6% (95%CI 57.6-91) with 6 deaths of which 4 were related to metastatic disease. Table reports subset analyses. Most frequently altered genes were PIK3CA and TP53 in the overall cohort (each 20%) and in the responders subgroup (each 29%). Conclusions: In our study, pts who achieved pCR had numerically greater TIL infiltrate in baseline samples and pCR was associated with reduced risk of recurrence. TILs did not increase in residual tumors after NAC. The independent predictive value of TILs warrants assessment in large cohorts.[Table: see text]

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