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Molecular Oncology Nov 2021Gastric cancer (GC) pathogenesis is complex and heterogeneous, reflecting morphological, molecular and genetic diversity. Diffuse gastric cancer (DGC) and intestinal... (Review)
Review
Gastric cancer (GC) pathogenesis is complex and heterogeneous, reflecting morphological, molecular and genetic diversity. Diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC) are the major histological types. GC may be sporadic or hereditary; sporadic GC is related to environmental and genetic low-risk factors and hereditary GC is caused by inherited high-risk mutations, so far identified only for the diffuse histotype. DGC phenotypic heterogeneity challenges the current understanding of molecular mechanisms underlying carcinogenesis. The definition of a DGC-specific mutational profile remains controversial, possibly reflecting the heterogeneity of DGC-related histological subtypes [signet-ring cell carcinoma (SRCC) and poorly cohesive carcinoma not otherwise specified (PCC-NOS)]. Indeed, DGC and DGC-related subtypes may present specific mutational profiles underlying the particularly aggressive behaviour and dismal prognosis of DGC vs IGC and PCC-NOS vs SRCC. In this systematic review, we revised the histological presentations, molecular classifications and approved therapies for gastric cancer, with a focus on DGC. We then analysed results from the most relevant studies, reporting mutational analysis data specifying mutational frequencies, and their relationship with DGC and IGC histological types, and with specific DGC subtypes (SRCC and PCC-NOS). We aimed at identifying histology-associated mutational profiles with an emphasis in DGC and its subtypes (DGC vs IGC; sporadic vs hereditary DGC; and SRCC vs PCC-NOS). We further used these mutational profiles to identify the most commonly affected molecular pathways and biological functions, and explored the clinical trials directed specifically to patients with DGC. This systematic analysis is expected to expose a DGC-specific molecular profile and shed light into potential targets for therapeutic intervention, which are currently missing.
Topics: Adenocarcinoma; Carcinoma, Signet Ring Cell; Germ-Line Mutation; Humans; Stomach Neoplasms
PubMed: 33724653
DOI: 10.1002/1878-0261.12948 -
Journal of Biomedical Optics Aug 2022Measurement and imaging of hemoglobin oxygenation are used extensively in the detection and diagnosis of disease; however, the applied instruments vary widely in their... (Review)
Review
SIGNIFICANCE
Measurement and imaging of hemoglobin oxygenation are used extensively in the detection and diagnosis of disease; however, the applied instruments vary widely in their depth of imaging, spatiotemporal resolution, sensitivity, accuracy, complexity, physical size, and cost. The wide variation in available instrumentation can make it challenging for end users to select the appropriate tools for their application and to understand the relative limitations of different methods.
AIM
We aim to provide a systematic overview of the field of hemoglobin imaging and sensing.
APPROACH
We reviewed the sensing and imaging methods used to analyze hemoglobin oxygenation, including pulse oximetry, spectral reflectance imaging, diffuse optical imaging, spectroscopic optical coherence tomography, photoacoustic imaging, and diffuse correlation spectroscopy.
RESULTS
We compared and contrasted the ability of different methods to determine hemoglobin biomarkers such as oxygenation while considering factors that influence their practical application.
CONCLUSIONS
We highlight key limitations in the current state-of-the-art and make suggestions for routes to advance the clinical use and interpretation of hemoglobin oxygenation information.
Topics: Hemoglobins; Oximetry; Spectrum Analysis; Tomography, Optical Coherence
PubMed: 35922891
DOI: 10.1117/1.JBO.27.8.080901 -
Frontiers in Molecular Biosciences 2023Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the... (Review)
Review
Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.
PubMed: 37614441
DOI: 10.3389/fmolb.2023.1215039 -
Neuro-oncology Advances 2022A comprehensive review and description of the clinical features that impact prognosis for patients with diffuse hemispheric glioma, H3 G34-mutant (G34-DHG) is needed....
BACKGROUND
A comprehensive review and description of the clinical features that impact prognosis for patients with diffuse hemispheric glioma, H3 G34-mutant (G34-DHG) is needed. Understanding survival and prognostic features is paramount for clinical advancements and patient care.
METHODS
PubMed, Embase, and Google Scholar were searched for English articles published between January 1, 2012 and June 30, 2021. Eligible studies included patient(s) of any age diagnosed with an H3 G34-mutant brain tumor with at least one measure of survival or progression. Patient-level data were pooled for analyses. This study was prospectively registered in PROSPERO (CRD42021267764) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
RESULTS
Twenty-seven studies met the criteria with a total of 135 patients included. Median age at diagnosis was 15.8 years (interquartile range [IQR]: 13.3-22.0) with 90% having localized disease. Co-occurring alterations included mutation in 93%, mutation in 88%, and promoter methylation in 70%. Median time-to-progression was 10.0 months (IQR: 6.0-18.0) and median overall survival was 17.3 months (95% CI: 15.0 to 22.9). The median time from progression to death was 5.0 months (IQR: 3.0-11.7). Factors associated with survival duration were age, as patients ≥18 y/o demonstrated longer survival (hazard ratio [HR] =2.05, 95% CI: 1.16 to 3.62), and degree of upfront resection, as near or gross-total resection demonstrated longer survival compared to those with less than near-total resection (HR = 3.75, 95% CI: 2.11 to 6.62).
CONCLUSION
This systematic review highlights available clinical data for G34-DHG demonstrating poor outcomes and important prognostic features, while serving as a baseline for future research and clinical trials.
PubMed: 36105387
DOI: 10.1093/noajnl/vdac133 -
International Journal of Molecular... Jun 2023Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state... (Review)
Review
Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy-namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories-clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets-and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target.
Topics: Adult; Humans; Animals; Mice; Molecular Targeted Therapy; beta Catenin; Mutation; Glioma; Brain Neoplasms; Oligodendroglioma; Isocitrate Dehydrogenase
PubMed: 37445633
DOI: 10.3390/ijms241310456 -
Research in Veterinary Science Dec 2022This review summarized published data about the ultrasound image of the spleen in dogs and cats described as diffuse heterogeneous echogenicity pattern and its... (Review)
Review
PURPOSE
This review summarized published data about the ultrasound image of the spleen in dogs and cats described as diffuse heterogeneous echogenicity pattern and its metaphorical terms honeycomb appearance, moth-eaten, lacy, marbled, and mottled.
METHODS
The following words were used to search the indexed articles: (Moth-eaten or mottled or marbled or reticulonodular or lacy) and (spleen or splenic) and (ultrasonography or ultrasound or ecography) and (cat or feline or dog or canine).
RESULTS
In total, 36 articles were initially found, of which 19 were selected. The reticulonodular pattern can be seen in healthy puppies. Although patients with various morbidities may present the pattern of splenic diffuse heterogeneous echogenicity, the higher prevalence in the data collected from the papers included in this review were natural infection by Babesia canis 100% (72/72) or by Ehrlichia canis 100% (17/17) or caused by torsion of the spleen 73.3% (11/15). This pattern is also associated with neoplasia both in dogs and cats.
CONCLUSIONS
The use of more precise descriptors, such as diffuse heterogeneous echogenicity pattern, reticular or reticular-nodular pattern, is preferred over metaphorical terms such as lacy, moth-eaten, mottled, or marbled pattern. Discrete diffuse heterogeneous splenic echogenicity patterns can be missed if ultrasonographic examinations are conducted with lower-frequency transducers. Although healthy puppies or patients with various morbidities may present the diffuse heterogeneous splenic echogenicity pattern, higher prevalences were reported in canine patients with natural infection by Babesia canis and Ehrlichia canis.
Topics: Cats; Dogs; Animals; Spleen; Cat Diseases; Dog Diseases; Ultrasonography
PubMed: 35933802
DOI: 10.1016/j.rvsc.2022.07.016 -
Journal of Dentistry Dec 2023The aim of this scoping review was to summarize and discuss the morphological features and associated factors of pulpal mineralizations (PMs) as described within the...
OBJECTIVE
The aim of this scoping review was to summarize and discuss the morphological features and associated factors of pulpal mineralizations (PMs) as described within the literature.
DATA
The study protocol was registered on the Open Science Framework platform and is available at the following link: https://osf.io/hfqwe. This scoping review was developed according to the PRISMA-ScR guidelines.
SOURCES
A literature search of four electronic databases was performed in SCOPUS, MEDLINE (PubMed), EMBASE and Word of Science, with the last search on May 29, 2023. Study selection was completed by two reviewers independently. Data was extracted regarding study characteristics, types, and features of PM and associated factors.
STUDY SELECTION
Of 1016 studies initially identified ten which qualified were included in this scoping review. Systemic and local factors that result in pulpal insult can contribute to the development of PMs. Three forms of PM have been reported, pulp stones, diffuse mineralizations, and mineralized ectopic connective tissue, with discrete and diffuse mineralization being the two clinically relevant forms. The different forms of PMs exhibit dissimilar morphological features.
CONCLUSION
Pulpal mineralizations exist in two clinically relevant forms: diffuse and discrete mineralizations and are likely associated with a pulpal insult.
CLINICAL SIGNIFICANCE
Understanding the morphology of dental pulp mineralization is the first step to expanding the knowledge of pulp mineralization and could result in improved diagnosis of endodontic pathosis.
Topics: Dental Pulp; Dental Pulp Calcification; Humans
PubMed: 37866408
DOI: 10.1016/j.jdent.2023.104745 -
Hematology (Amsterdam, Netherlands) Dec 2023The role of subcutaneous (SC) rituximab in the efficacy and safety to non-Hodgkin lymphoma (NHL) is not clear enough. The purpose of this study was to conduct a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The role of subcutaneous (SC) rituximab in the efficacy and safety to non-Hodgkin lymphoma (NHL) is not clear enough. The purpose of this study was to conduct a systematic review and meta-analysis, to assess the efficacy and safety of subcutaneous rituximab to NHL.
METHOD
A full-scale search was carried out based on the set search terms in PubMed, Web of Science, Embase and Cochrane CENTRAL until 12 October 2022 to identify relevant studies of subcutaneous rituximab for NHL. The efficacy and safety outcomes included complete response (CR) plus unconfirmed complete response (CRu), adverse events (AEs), grade ≥3 AEs, serious adverse events (SAEs), administration-related reactions (ARRs), adverse reaction rates.
RESULTS
From a total of 758 studies, 9 trials were eligible. The CR/CRu of patients with NHL receiving SC rituximab was 57%, 55% for Diffuse large B-cell lymphoma (DLBCL) and 54% for Follicular lymphoma (FL). The meta-analysis performed on safety demonstrated that AEs of NHL patients with SC rituximab was 85%, grade ≥3 AEs was 38%, SAE was 27% and ARR was 33%. The result also showed that SC rituximab had a high risk of neutropenia and nausea.
CONCLUSION
For NHL patients, there is no significant difference in the efficacy between subcutaneous rituximab and conventional therapy, while subcutaneous injection can shorten exposure time in the hospital and reduce the risk of infection.
Topics: Humans; Rituximab; Lymphoma, Non-Hodgkin; Treatment Outcome; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38010876
DOI: 10.1080/16078454.2023.2284047 -
Neuroscience and Biobehavioral Reviews Jan 2022Although negative early life experiences are associated with an increased risk of developing psychopathology, some individuals exposed to childhood adversity demonstrate... (Review)
Review
Although negative early life experiences are associated with an increased risk of developing psychopathology, some individuals exposed to childhood adversity demonstrate psychological resilience. Little is known about the neural correlates of resilience, especially in young people. To address this gap, we conducted a systematic review of neuroimaging studies of resilience in youth. The PubMed, Web of Science, Scopus, and PsycINFO databases were searched; 5,482 studies were identified. Following title/abstract screening, and full reading of the remaining articles, 22 studies based on 19 unique datasets were included. We found preliminary evidence that resilience is associated with structural, functional, and connectivity differences in young people, as assessed using structural and functional MRI and diffusion tensor imaging methods. Despite heterogeneity in definitions/assessment of resilience and a limited number of studies, the neuroimaging literature suggests some convergence across modalities regarding brain regions linked to resilience (especially the prefrontal cortex). Future studies would benefit from adopting longitudinal designs, broader conceptualisations of resilience that capture the impact of adversity exposure, and a dimensional approach to psychopathology.
Topics: Adolescent; Brain; Diffusion Tensor Imaging; Humans; Magnetic Resonance Imaging; Neuroimaging; Resilience, Psychological
PubMed: 34740756
DOI: 10.1016/j.neubiorev.2021.11.001 -
Journal of Neurosurgery. Pediatrics Dec 2023Diffuse intrinsic pontine gliomas (DIPGs) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy can obtain molecular and genetic information for...
OBJECTIVE
Diffuse intrinsic pontine gliomas (DIPGs) are aggressive and malignant tumors of the brainstem. Stereotactic biopsy can obtain molecular and genetic information for diagnostic and potentially therapeutic purposes. However, there is no consensus on the safety of biopsy or effect on survival. The authors aimed to characterize neurological risk associated with and the effect of stereotactic biopsy on survival among patients with DIPGs.
METHODS
A systematic review was performed in accordance with PRISMA guidelines to identify all studies examining pediatric patients with DIPG who underwent stereotactic biopsy. The search strategy was deployed in PubMed, Embase, and Scopus. The quality of studies was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system, and risk of bias was evaluated with the Cochrane Risk of Bias in Nonrandomized Studies-of Interventions tool. Bibliographic, demographic, clinical, and outcome data were extracted from studies meeting inclusion criteria.
RESULTS
Of 2634 resultant articles, 13 were included, representing 192 patients undergoing biopsy. The weighted mean age at diagnosis was 7.5 years (range 0.5-17 years). There was an overall neurosurgical complication rate of 13.02% (25/192). The most common neurosurgical complication was cranial nerve palsy (4.2%, 8/192), of which cranial nerve VII was the most common (37.5%, 3/8). The second most common complication was perioperative hemorrhage (3.6%, 7/192), followed by hemiparesis (2.1%, 4/192), speech disorders (1.6%, 3/192) such as dysarthria and dysphasia, and movement disorders (1.0%, 2/192). Hydrocephalus was less commonly reported (0.5%, 1/192), and there were no complications relating to wound infection/dehiscence (0%, 0/192) or CSF leak (0%, 0/192). No mortality was specifically attributed to biopsy. Diagnostic yield of biopsy revealed a weighted mean of 97.4% (range 91%-100%). Of the studies reporting survival data, 37.6% (32/85) of patients died within the study follow-up period (range 2 weeks-48 months). The mean overall survival in patients undergoing biopsy was 9.73 months (SD 0.68, median 10 months, range 6-13 months).
CONCLUSIONS
Children with DIPGs undergoing biopsy have mild to moderate rates of neurosurgical complications and no excessive morbidity. With reasonably acceptable surgical risk and high diagnostic yield, stereotactic biopsy of DIPGs can allow for characterization of patient-specific molecular and genetic features that may influence prognosis and the development of future therapeutic strategies.
Topics: Humans; Child; Infant; Child, Preschool; Adolescent; Glioma; Diffuse Intrinsic Pontine Glioma; Brain Stem Neoplasms; Biopsy
PubMed: 37724839
DOI: 10.3171/2023.7.PEDS22462