scholarly journals Proteins Structure Models in the Evaluation of Novel Variant (C.472_477del) in the MOCS2 Gene

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 821
Author(s):  
Aleksandra Jezela-Stanek ◽  
Witold Blaz ◽  
Artur Gora ◽  
Malgorzata Bochenska ◽  
Katarzyna Kusmierska ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Treatment Options ◽  
Molecular Defect ◽  
Intractable Seizures ◽  
Craniofacial Dysmorphism ◽  
Unknown Significance ◽  
Novel Variant ◽  
Original Insight ◽  
Deficiency Type ◽  
Cofactor Deficiency

(1) Background: Molybdenum cofactor deficiency type B (MOCODB, #252160) is a rare autosomal recessive metabolic disorder characterized by intractable seizures of neonatal-onset, muscular spasticity, accompanying with hypouricemia, elevated urinary sulfite levels and craniofacial dysmorphism. Thirty-five patients were reported to date. (2) Methods: Our paper aimed to delineate the disease genotype by presenting another patient, in whom a novel, in-frame variant within the MOCS2 gene was identified. (3) Results: Exome sequencing led to the identification of a novel variant in the MOCS2 gene-c.472_477del of unknown significance (VUS). (4) Conclusions: To prove the clinical significance of the mentioned variant, analysis of the possible mutation consequences on molecular level with the use of the available crystal structure of the human molybdopterin synthase complex was of great importance. Moreover, a potential pathomechanism resulting from a molecular defect was presented, giving original insight into the current knowledge on this rare disease, including treatment options.

scholarly journals Severe cystic degeneration and intractable seizures in a newborn with molybdenum cofactor deficiency type B

2019 ◽  
Vol 18 ◽  
pp. 11-13 ◽  
Author(s):  
Fady Hannah-Shmouni ◽  
Lauren MacNeil ◽  
Murray Potter ◽  
Rebekah Jobling ◽  
Grace Yoon ◽  
...  
Keyword(s):  
Molybdenum Cofactor ◽  
Cystic Degeneration ◽  
Type B ◽  
Molybdenum Cofactor Deficiency ◽  
Intractable Seizures ◽  
Deficiency Type ◽  
Cofactor Deficiency

Pulmonary Manifestations in Rheumatoid Arthritis, Psoriatic Arthritis and Peripheral Spondyloarthritis Prevalence, Diagnostic Approach and Treatment Options

2020 ◽  
Vol 16 ◽  
Author(s):  
Daniel Dejcman ◽  
Valentin Sebastian Schäfer ◽  
Dirk Skowasch ◽  
Carmen Pizarro ◽  
Andreas Krause ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Lung Disease ◽  
Current Knowledge ◽  
Treatment Options ◽  
Pulmonary Diseases ◽  
Chronic Obstructive ◽  
Pulmonary Manifestations ◽  
Major Cluster ◽  
Peripheral Spondyloarthritis

: Interstitial lung disease (ILD) is the most common form of pulmonary impairment in patients with rheumatoid arthritis (RA). However, patients with RA or other arthritic diseases such as psoriatic arthritis (PsA) or peripheral spondyloarthritis (pSpA) may develop several other pulmonary diseases such as chronic obstructive lung disease (COPD) with a higher risk than patients without arthritis. The article at hand aims at summarizing the current knowledge on the prevalence of pulmonary diseases in the above-mentioned forms of arthritis, the challenges for prevalence studies and detecting pulmonary diseases in patients with arthritis as well as possible treatment options. Dyspnea, cough or other pulmonary symptoms or findings in arthritis patients should prompt gradual diagnostic procedures considering pulmonary manifestations as a major cluster of differential diagnosis. Considering its poor prognosis and morbidity burden, RA-ILD needs to be ruled out. Treatment of manifestations often lacks solid evidencebased guidelines and referrals to specialized centers are often necessary.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

2020 ◽  
Author(s):  
Guanghui Xu ◽  
Yuhao Wang ◽  
Hushan Zhang ◽  
Xueke She ◽  
Jianjun Yang
Keyword(s):  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
The Body ◽  
Low Grade ◽  
Ablative Therapies ◽  
Cancer Types ◽  
New Treatment ◽  
Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

scholarly journals Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 909
Author(s):  
Krzysztof Kotowski ◽  
Jakub Rosik ◽  
Filip Machaj ◽  
Stanisław Supplitt ◽  
Daniel Wiczew ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Treatment Options ◽  
Protein Structures ◽  
New Drugs ◽  
Proliferating Cells ◽  
Cancer Tissues ◽  
The Impact ◽  
Rate Limiting ◽  
Synthesis And Degradation

Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. However, most recent studies have focused on an increased expression of PFKFB3 and PFKFB4 in cancer tissues and their role in carcinogenesis. In this review, we summarize our current knowledge on all PFKFB genes and protein structures, and emphasize important differences between the isoenzymes, which likely affect their kinase/phosphatase activities. The main focus is on the latest reports in this field of cancer research, and in particular the impact of PFKFB3 and PFKFB4 on tumor progression, metastasis, angiogenesis, and autophagy. We also present the most recent achievements in the development of new drugs targeting these isozymes. Finally, we discuss potential combination therapies using PFKFB3 inhibitors, which may represent important future cancer treatment options.

scholarly journals Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

2021 ◽  
Vol 18 (4) ◽  
pp. 1692
Author(s):  
Akylbek Sydykov ◽  
Argen Mamazhakypov ◽  
Abdirashit Maripov ◽  
Djuro Kosanovic ◽  
Norbert Weissmann ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
High Altitude ◽  
Clinical Experience ◽  
Current Knowledge ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Treatment Options ◽  
Right Heart Failure ◽  
Channel Blockers ◽  
The Right ◽  
Extensive Clinical Experience

Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options.

Genomic structure and mutational spectrum of the bicistronic MOCS1 gene defective in molybdenum cofactor deficiency type A

1998 ◽  
Vol 103 (6) ◽  
pp. 639-644 ◽  
Author(s):  
J. Reiss ◽  
Ernst Christensen ◽  
Gerhard Kurlemann ◽  
Marie-Therese Zabot ◽  
Claude Dorche
Keyword(s):  
Genomic Structure ◽  
Type A ◽  
Molybdenum Cofactor ◽  
Molybdenum Cofactor Deficiency ◽  
Mutational Spectrum ◽  
Deficiency Type ◽  
Cofactor Deficiency

scholarly journals Cytoreductive Surgery for Peritoneal Carcinomatosis from Gastric Cancer: Technical Details

2021 ◽  
Vol 10 (22) ◽  
pp. 5263
Author(s):  
Thomas Boerner ◽  
Pompiliu Piso
Keyword(s):  
Gastric Cancer ◽  
Peritoneal Carcinomatosis ◽  
Cytoreductive Surgery ◽  
Postoperative Morbidity ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Modalities ◽  
Locoregional Treatment ◽  
Surgical Expertise ◽  
Technical Details

Due to limited systemic treatment options, peritoneal carcinomatosis of gastric origin is still associated with a dismal outcome and is claimed a terminal disease. In the past, surgery had not been considered as a potential treatment option. However, there is emerging evidence that in selected patients, locoregional treatment modalities including cytoreductive surgery of peritoneal carcinomatosis can improve survival in patients with gastric cancer. These operative procedures are complex and challenging, and a high surgical expertise of the treating physician is necessary to prevent major postoperative morbidity and mortality with a delay of further systemic therapy. This review summarizes our current knowledge and personal experience regarding the techniques of cytoreductive surgery for peritoneal metastasis of gastric origin.

scholarly journals Tumor-Intrinsic Mechanisms Regulating Immune Exclusion in Liver Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Katherine E. Lindblad ◽  
Marina Ruiz de Galarreta ◽  
Amaia Lujambio
Keyword(s):  
Liver Cancer ◽  
Rational Design ◽  
Immune Escape ◽  
Current Knowledge ◽  
Treatment Options ◽  
Health Concern ◽  
Patient Stratification ◽  
Tumor Immune Evasion ◽  
Advanced Hcc ◽  
Liver Cancers

Representing the fourth leading cause of cancer-related mortality worldwide, liver cancers constitute a major global health concern. Hepatocellular carcinoma (HCC), the most frequent type of liver cancer, is associated with dismal survival outcomes and has traditionally had few treatment options available. In fact, up until 2017, treatment options for advanced HCC were restricted to broad acting tyrosine kinase inhibitors, including Sorafenib, which has been the standard of care for over a decade. Since 2017, a multitude of mono- and combination immunotherapies that include pembrolizumab, nivolumab, ipilumumab, atezolizumab, and bevacizumab have been FDA-approved for the treatment of advanced HCC with unprecedented response rates ranging from 20 to 30% of patients. However, this also means that ~70% of patients do not respond to this treatment and currently very little is known regarding mechanisms of action of these immunotherapies as well as predictors of response to facilitate patient stratification. With the recent success of immunotherapies in HCC, there is a pressing need to understand mechanisms of tumor immune evasion and resistance to these immunotherapies in order to identify biomarkers of resistance or response. This will enable better patient stratification as well as the rational design of combination immunotherapies to restore sensitivity in resistant patients. The aim of this review is to summarize the current knowledge to date of tumor-intrinsic mechanisms of immune escape in liver cancer, specifically in the context of HCC.

scholarly journals Clinical study of multiple myeloma and treatment responses in a tertiary care centre

2021 ◽  
Vol 9 (11) ◽  
pp. 3356
Author(s):  
Immanni S. M. Giridhar ◽  
C. Deepak Yadlapalli ◽  
Muralidhar Gullipalli ◽  
Venkatesh Mushini ◽  
Yerraguntla S. Sarma ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Treatment Options ◽  
Tertiary Care ◽  
Elevated Serum ◽  
Staging System ◽  
Stage Iiib ◽  
Common Symptom ◽  
Tertiary Care Centre ◽  
Incurable Disease ◽  
Unknown Significance

Background: Multiple myeloma (MM) evolves from Monoclonal gammopathy of unknown significance (MGUS), a premalignant clinical condition. Second to non-Hodgkin’s lymphoma, MM is the most common haematological malignancy. The aim of the study was to review the clinical profile and response of individuals treated for MM from this part of country.Methods: We evaluated data of patients with MM managed between 2013 and 2019 at a tertiary care cancer hospital in Rajamahenderi, India. Data regarding demographic variables, clinical features, disease characteristics and treatment details were collected and analysed.Results: Total of 54 patients with MM were managed. Mean age was 59.4 years. Males accounted for 63%. Bone pain (90%) was the most common symptom. Elevated serum creatinine was noted in 16.7% and M band in 42 (77.8%). X-ray of skull showed lytic lesions in 41 (75.9%). Mean haemoglobin value was 8.8±1.9 g/dl and serum calcium was 9.12 mg/dl. Majority of subjects, 44 (81.48%) belong to stage IIIA, 9 (16.67%) to stage IIIB, and 1.85% to stage IIA of Durie Salmon staging system. No response was noted in 17 (31.5%), 4 (7.4%) subjects had a progressive disease even on treatment, and 8 (14.8%) subjects had a very good partial response. Median survival of subjects belonging to DSS stage II was 17 months, IIIA was 11.037 months and stage IIIB was 17.463 months.Conclusions: MM has an early onset in India. Though MM is an incurable disease, many promising treatment options are there which lead to increase in survival. Early treatment helps in improving mortality rates, better quality of life and decreases disease burden.

scholarly journals Thin Air Resulting in High Pressure: Mountain Sickness and Hypoxia-Induced Pulmonary Hypertension

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Jan Grimminger ◽  
Manuel Richter ◽  
Khodr Tello ◽  
Natascha Sommer ◽  
Henning Gall ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
High Altitude ◽  
Hypobaric Hypoxia ◽  
Current Knowledge ◽  
Treatment Options ◽  
Acute Response ◽  
Mechanisms Of Adaptation ◽  
Mountain Sickness

With rising altitude the partial pressure of oxygen falls. This phenomenon leads to hypobaric hypoxia at high altitude. Since more than 140 million people permanently live at heights above 2500 m and more than 35 million travel to these heights each year, understanding the mechanisms resulting in acute or chronic maladaptation of the human body to these circumstances is crucial. This review summarizes current knowledge of the body’s acute response to these circumstances, possible complications and their treatment, and health care issues resulting from long-term exposure to high altitude. It furthermore describes the characteristic mechanisms of adaptation to life in hypobaric hypoxia expressed by the three major ethnic groups permanently dwelling at high altitude. We additionally summarize current knowledge regarding possible treatment options for hypoxia-induced pulmonary hypertension by reviewing in vitro, rodent, and human studies in this area of research.

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