Publications by authors named "David Romano"
The RAS-RAF-MEK-ERK pathway is hyperactivated in most malignant melanomas, and mutations in BRAF or NRAS account for most of these cases. BRAF inhibitors (BRAFi) are highly efficient for treating patients with BRAF mutations, but tumours frequently acquire resistance within a few months. Multiple resistance mechanisms have been identified, due to mutations or network adaptations that revive ERK signalling.
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- - Hypercoagulable disorders (HCDs) can be genetic or developed over time, both increasing the risk of dangerous blood clots known as venous thromboembolic events (VTEs).
- - Many patients with HCD only learn about their condition after experiencing complications from surgery.
- - It's advised that anyone with concerns about HCD be referred to a hematology specialist for proper evaluation and treatment; additionally, using tourniquets in surgeries for HCD patients is discouraged due to potential risks.
Article Synopsis
- The study aimed to evaluate the effectiveness of two C-Arm draping methods in reducing contamination compared to traditional methods used in an operating room setup.
- Researchers simulated an OR environment with various draping techniques and measured contamination levels using fluorescent powder and black light after imaging cycles.
- Results showed that the split drape significantly reduced contamination by 99.5%, while the proprietary close-fitting drape had a 71.3% reduction but was not statistically significant, highlighting the split drape as a more effective option for minimizing infection risk.
Article Synopsis
- There is an increasing incidence of neuroendocrine neoplasms (NENs), but current treatments are largely ineffective due to limited understanding of these tumors and their resistance to common therapies.
- Researchers engineered oxaliplatin-resistant QGP-1 cells to study the molecular mechanisms behind this resistance and identified specific hyperactivated kinases linked to acquired resistance, particularly in the FGFR and ERK pathways.
- The findings suggest that inhibiting FGFR can reduce ERK signaling and cell viability, providing potential new avenues for targeted therapies in treating NENs.
Relevance of neuroendocrine tumours models assessed by kinomic profiling.
Ann Endocrinol (Paris)
June 2019
Article Synopsis
- - Despite a significant rise in neuroendocrine tumors (NETs), current treatments are lacking due to limited understanding and few actionable mutations within these tumors compared to other cancer types.
- - Existing in vitro models for studying NETs have raised concerns about their reliability, as they may not accurately reflect the biology of NETs or support effective treatment strategies.
- - To improve the study of NETs, advanced technologies focusing on kinases and their signaling pathways are proposed, which could help identify relevant actions for targeted therapies and improve patient trials.
Article Synopsis
- Fragile X syndrome (FXS) is the most common inherited cause of developmental disability, with significant variation in cognitive and behavioral outcomes among affected individuals.
- A study involving 42 young boys with FXS used T1-weighted MRI scans and assessments to explore early brain growth and identify clinically meaningful subgroups based on structural brain data.
- The analysis revealed two distinct subgroups, with one showing consistently higher cognitive and adaptive functioning, indicating that identifying these phenotypes could help predict outcomes and inform targeted therapies for FXS and potentially other neuropsychiatric disorders.
Pasireotide is a somatostatin analog (SSA) that targets somatostatin receptor subtype 1 (SST1), SST2, SST3, and SST5 with a high affinity. Pasireotide has a better antisecretory effect in acromegaly, Cushing's disease, and neuroendocrine tumors than octreotide. In this study, we compared the effects of pasireotide to those of octreotide on meningioma primary cell cultures, both alone and in combination with the mTOR inhibitor everolimus.
View Article and Find Full Text PDFTherapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus recently obtained approval from the Food and Drug Administration for the treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs). Despite its promising antitumor efficacy observed in cell lines, clinical benefit for patients is unsatisfactory.
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- Meningiomas, a type of brain tumor, have a receptor called SST2 that can be targeted with a drug called octreotide.
- A study tested octreotide on 80 meningiomas and found that it slowed down tumor cell growth but didn't kill the cells.
- The results suggest that octreotide might help manage these tumors by limiting their growth, especially in those with high levels of the SST2 receptor, rather than making the tumors smaller.
RASSF enzymes act as key apoptosis activators and tumor suppressors, being downregulated in many human cancers, although their exact regulatory roles remain unknown. A key downstream event in the RASSF pathway is the regulation of MST kinases, which are main effectors of RASSF-induced apoptosis. The regulation of MST1/2 includes both homo- and heterodimerization, mediated by helical SARAH domains, though the underlying molecular interaction mechanism is unclear.
View Article and Find Full Text PDFThe BRAF proto-oncogene serine/threonine-protein kinase, known as BRAF, belongs to the RAF kinase family. It regulates the MAPK/ERK signalling pathway affecting several cellular processes such as growth, survival, differentiation, and cellular transformation. BRAF is mutated in ~8% of all human cancers with the V600E mutation constituting ~90% of mutations.
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- The extensor digitorum brevis manus (EDBM) is a rare extensor muscle located on the back of the wrist and hand, first described in 1734 and occurring in about 2% of the population.
- Most extensor muscle variants of the hand aren't clinically significant, and there's limited research on them, mainly from studies on cadavers or individual cases.
- This case report discusses a young patient who underwent successful surgery to remove the symptomatic EDBM after conservative treatments failed, and it suggests a management plan for similar cases.
Article Synopsis
- BRAF is part of the RAS-ERK signaling pathway, which is crucial for the cancer-promoting effects of mutated BRAF, and it can also negatively regulate the EGFR through the tumor suppressor MIG-6.
- MIG-6 reduces malignant transformation caused by oncogenic BRAF, but does not directly regulate BRAF's activity; instead, it acts through RAS-ERK signaling to inhibit EGFR activation.
- In papillary thyroid cancer, the presence of the BRAF V600E mutation is linked to higher MIG-6 levels and lower EGFR activation, suggesting a feedback loop that could influence disease aggressiveness based on MIG-6 expression levels.
Article Synopsis
- The study investigates surgical outcomes after ankle fracture fixation in active military personnel, focusing on return to running and occupational stability.
- It analyzed data from 72 service members who underwent ankle fixation, revealing that 64% returned to running, while 17% were medically separated due to pain issues.
- The findings suggest that a high percentage (83%) remained on active duty after three years, indicating relatively positive outcomes for this population post-surgery.
How do biochemical signaling pathways generate biological specificity? This question is fundamental to modern biology, and its enigma has been accentuated by the discovery that most proteins in signaling networks serve multifunctional roles. An answer to this question may lie in analyzing network properties rather than individual traits of proteins in order to elucidate design principles of biochemical networks that enable biological decision-making. We discuss how this is achieved in the MST2/Hippo-Raf-1 signaling network with the help of mathematical modeling and model-based analysis, which showed that competing protein interactions with affinities controlled by dynamic protein modifications can function as Boolean computing devices that determine cell fate decisions.
View Article and Find Full Text PDFCompact and informative representation of functional connectivity for predictive modeling.
Med Image Comput Comput Assist Interv
November 2014
Article Synopsis
- Resting state functional connectivity can help predict neurological and psychiatric illnesses, offering a promising diagnostic tool.
- The paper presents a compact representation of connectivity that simplifies predictive modeling without needing pre-defined regions of interest.
- Experiments show this new representation improves accuracy and aligns well with existing physiological knowledge.
Article Synopsis
- The Hippo/MST2 pathway is a crucial signaling system that regulates organ size in fruit flies and has expanded functions in mammals, particularly in cancer biology.
- Disruptions in the MST2 pathway are linked to tumor development through their impact on cell processes like apoptosis and the cell cycle, and they interact with other signaling pathways.
- This review focuses on how cancer-related changes, like mutations in RAS and PI3K/Akt, affect MST2 activity, along with mechanisms such as protein-protein interactions and gene silencing that lead to its down-regulation in cancer.
Signal transduction requires the coordination of activities between different pathways. In mammalian cells, Raf-1 regulates the MST-LATS and MEK-ERK pathways. We found that a complex circuitry of competing protein interactions coordinates the crosstalk between the ERK and MST pathways.
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- Fragile X syndrome (FXS), caused by mutations in the FMR1 gene, is the leading inherited cause of developmental disabilities and is linked to autism.
- A study analyzed brain imaging and behavior of 52 young boys with FXS, revealing two distinct subgroups with significant differences in brain structure, IQ, and autism-related behaviors.
- The findings indicate that FXS can manifest in two separate biological and clinical phenotypes, highlighting the effectiveness of topological data analysis (TDA) in exploring neuropsychiatric disorders.
Article Synopsis
- Feral swine, which are wild hogs, were controlled at a large Air Force base in Florida to protect delicate wetlands.
- A study tracked the pig population from 2008 to 2012, showing that the number of swine decreased significantly after control measures began in 2009.
- The study also monitored other animals like coyotes and endangered species, but outside factors like military activities made it hard to keep control efforts steady.
Article Synopsis
- The study looked back at data to see how different factors like age, gender, and other health issues affect recovery after a hip fracture.
- It found that most people with hip fractures were older, mostly women, and that 4.5% of them died from their injuries while 12.5% had complications.
- Significant factors affecting health outcomes included conditions like dialysis, being in shock, and how quickly they got surgery after the fracture.
Article Synopsis
- Raf-1 is an important activator of the ERK pathway that is regulated by the cAMP signaling system, specifically through the PKA enzyme that inhibits Raf-1 by phosphorylation.
- PDE8A, a cAMP-degrading phosphodiesterase, binds tightly to Raf-1, preventing PKA from inhibiting it and enhancing Raf-1's ability to activate ERK signaling.
- Disrupting the interaction between PDE8A and Raf-1 reduces ERK activation, with similar effects observed in genetically modified mice and Drosophila, suggesting that PDE8A plays a key role in regulating Raf-1 signaling in certain cells.
K-Ras is frequently mutated in human cancers. Mutant (mt) K-Ras can stimulate both oncogenic transformation and apoptosis through activation of extracellular signal-regulated kinase (ERK) and AKT pathways and the MST2 pathway, respectively. The biological outcome is determined by the balance and cross talk between these pathways.
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- - K-Ras mutations are common in colorectal cancer (CRC) and can trigger apoptosis through their interaction with the tumor suppressor RASSF1A, activating the MST2-LATS1 pathway, which stabilizes p53.
- - While mutant K-Ras promotes apoptosis, it also activates the EGF receptor (EGFR), which can inhibit this apoptotic process and requires the presence of the normal K-Ras allele for this protective effect.
- - Research shows a negative correlation between K-Ras mutation and MST2 expression in CRC patients, with tumors expressing both mutant K-Ras and MST2 having higher apoptosis rates, indicating that the wild-type K-Ras allele helps support tumor transformation by the mutant allele.
Article Synopsis
- The study is a retrospective review aimed at examining the incidence and risk factors of lumbar spine fractures among US military personnel from 2001 to 2010.
- Using healthcare database codes, the research identifies demographic information (such as race, sex, and branch of service) of individuals with these fractures and compares it to the overall military population.
- Results show a low incidence of 0.38 per 1000 person-years, with significant predictors being male sex, white race, enlisted status, service in the Army or Marines, and age groups of 20-24 or over 40.