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Diagnostics (Basel, Switzerland) May 2024Microsatellite Instability (MSI-H) occurs in approximately 15% of non-metastatic colon cancers, influencing patient outcomes positively compared to microsatellite stable... (Review)
Review
Microsatellite Instability (MSI-H) occurs in approximately 15% of non-metastatic colon cancers, influencing patient outcomes positively compared to microsatellite stable (MSS) cancers. This systematic review focuses on the prognostic significance of KRAS, NRAS, and BRAF mutations within MSI-H colon cancer. Through comprehensive searches in databases like MEDLINE, EMBASE, and others until 1 January 2024, we selected 8 pertinent studies from an initial pool of 1918. These studies, encompassing nine trials and five observational studies involving 13,273 patients, provided insights into disease-free survival (DFS), survival after recurrence, and overall survival. The pooled data suggest that while KRAS and BRAF mutations typically predict poorer outcomes in MSS colorectal cancer, their impact is less pronounced in MSI contexts, with implications varying across different stages of cancer and treatment responses. In particular, adverse effects of these mutations manifest significantly upon recurrence rather than affecting immediate DFS. Our findings confirm the complex interplay between genetic mutations and MSI status, emphasizing the nuanced role of MSI in modifying the prognostic implications of KRAS, NRAS, and BRAF mutations in colon cancer. This review underscores the importance of considering MSI alongside mutational status in the clinical decision-making process, aiming to tailor therapeutic strategies more effectively for colon cancer patients.
PubMed: 38786299
DOI: 10.3390/diagnostics14101001 -
Journal of Diabetes Investigation Mar 2022Type 2 diabetes is known as a risk factor for pancreatic cancer (PC). Various genetic and environmental factors cause both these global chronic diseases. The mechanisms... (Review)
Review
Type 2 diabetes is known as a risk factor for pancreatic cancer (PC). Various genetic and environmental factors cause both these global chronic diseases. The mechanisms that define their relationships are complex and poorly understood. Recent studies have implicated that metabolic abnormalities, including hyperglycemia and hyperinsulinemia, could lead to cell damage responses, cell transformation, and increased cancer risk. Hence, these kinds of abnormalities following molecular events could be essential to develop our understanding of this complicated link. Among different molecular events, focusing on shared signaling pathways including metabolic (PI3K/Akt/mTOR) and mitogenic (MAPK) pathways in addition to regulatory mechanisms of gene expression such as those involved in non-coding RNAs (miRNAs, circRNAs, and lncRNAs) could be considered as powerful tools to describe this association. A better understanding of the molecular mechanisms involved in the development of type 2 diabetes and pancreatic cancer would help us to find a new research area for developing therapeutic and preventive strategies. For this purpose, in this review, we focused on the shared molecular events resulting in type 2 diabetes and pancreatic cancer. First, a comprehensive literature review was performed to determine similar molecular pathways and non-coding RNAs; then, the final results were discussed in more detail.
Topics: Animals; Diabetes Mellitus, Type 2; Humans; MAP Kinase Signaling System; MicroRNAs; Pancreatic Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; RNA, Long Noncoding; TOR Serine-Threonine Kinases
PubMed: 34859606
DOI: 10.1111/jdi.13727 -
Genetics Research 2022Accumulating evidence indicates that the expression and/or variants of several genes play an essential role in the progress of colorectal cancer (CRC). The current study... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Accumulating evidence indicates that the expression and/or variants of several genes play an essential role in the progress of colorectal cancer (CRC). The current study is a meta-analysis undertaken to estimate the prognosis and survival associated with , , , , , and genes among CRC patients.
METHODS
The authors searched PubMed, EMBASE, and Science Direct for relevant reports published between 2000 and 2020 and analyzed them to determine any relationship between the (immunohistochemically/sequencing-detected) gene expression and variants of the selected genes and the survival of CRC patients.
RESULTS
The analysis included 34,074 patients from 64 studies. To evaluate association, hazard ratios (HRs) were estimated for overall survival (OS) or disease-free survival (DFS), with a 95% confidence interval (CIs). Pooled results showed that overexpression, mutation, or 4 loss of expression, mutations, and expression were associated with shorter OS. overexpression (HR: 0.137 (95% CI: 0.131-0.406)), loss of expression of or 4 (HR: 0.449 (95% CI: 0.146-0.753)), the mutations of (HR: 0.179 (95% CI: 0.126-0.485)), and expression (HR: 0.485 (95% CI: 0.772-0.198)) also presented risk for shorter DFS.
CONCLUSIONS
The present meta-analysis indicates that overexpression or underexpression and variants of , , 4, , and genes potentially acted as unfavorable biomarkers for the prognosis of CRC. The gene was not associated with prognosis.
Topics: Colorectal Neoplasms; Cyclin D1; Genes, bcl-1; Humans; Prognosis; Smad3 Protein; Tumor Suppressor Protein p53; beta Catenin
PubMed: 36072013
DOI: 10.1155/2022/5338956 -
JDR Clinical and Translational Research Apr 2021The use of recombinant human platelet-derived growth factor-BB (rhPDGF) has received Food and Drug Administration approval for the treatment of periodontal and...
AIM
The use of recombinant human platelet-derived growth factor-BB (rhPDGF) has received Food and Drug Administration approval for the treatment of periodontal and orthopedic bone defects and dermal wound healing. Many studies have investigated its regenerative potential in a variety of other oral clinical indications. The aim of this systematic review was to assess the efficacy, safety, and clinical benefit of recombinant human platelet-derived growth factor (rhPDGF) use for alveolar bone and/or soft tissue regeneration.
MATERIAL AND METHODS
Comprehensive electronic and manual literature searches according to the PRISMA guidelines were performed to identify interventional and observational studies evaluating the regenerative applications of rhPDGF-BB. The primary outcomes were the safety, efficacy, and overall clinical benefit of rhPDGF use in oral regenerative procedures.
RESULTS
Sixty-three human clinical studies (mean ± SD follow-up period of 10.7 ± 3.3 mo) were included in the qualitative analysis. No serious adverse effects were reported in any of the 63 studies, aside from the postoperative complications routinely associated with surgical therapy. Use of rhPDGF was shown to be beneficial when combined with allografts, xenografts, and alloplasts (the latter tricalcium phosphate [β-TCP]) for the treatment of periodontal defects and gingival recession. The use of rhPDGF also led to favorable clinical outcomes when combined with allografts or xenografts for guided bone regeneration (GBR) and alveolar ridge preservation. While favorable clinical results support the use of the combination of rhPDGF plus allograft or xenograft for GBR, ARP, and sinus floor augmentation, current data support the use of rhPDGF and alloplasts (e.g., β-TCP) only in periodontal defects and gingival recession.
CONCLUSIONS
Based on the clinical evidence, rhPDGF is safe and provides clinical benefits when used in combination with bone allografts, xenograft, or β-TCP for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for GBR and ARP (PROSPERO CRD42020142446).
KNOWLEDGE TRANSFER STATEMENT
Clinicians should be aware that rhPDGF is a safe and effective approach for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for bone regeneration and alveolar ridge preservation. With consideration of cost and patient preference, this result could lead to more appropriate therapeutic decisions.
Topics: Alveolar Bone Loss; Becaplermin; Humans; Proto-Oncogene Proteins c-sis; Recombinant Proteins; Sinus Floor Augmentation; United States
PubMed: 32392438
DOI: 10.1177/2380084420921353 -
Medical Oncology (Northwood, London,... Apr 2023Ameloblastoma in 66% of the cases harbor a somatic mutation of the "mitogen-activated protein kinase" signaling pathway (BRAF V600E). In V600E mutations, BRAF is in the... (Review)
Review
BACKGROUND
Ameloblastoma in 66% of the cases harbor a somatic mutation of the "mitogen-activated protein kinase" signaling pathway (BRAF V600E). In V600E mutations, BRAF is in the permanent "on" state and relays the growth-promoting signals independently of the EGFR pathway. Therefore, mutant BRAF represents a target for handful of new drugs.
METHODS
We conducted a literature search, with the search terms "Vemurafenib, Dabrafenib, Ameloblastoma, and BRAF." These included seven case reports with nine patients who underwent monotherapy with Dabrafenib or Vemurafenib or combination therapy with Dabrafenib and Trametinib.
RESULTS
The patients age ranges from 10 years up to 86 years. The distribution of women and men is 4:5. Patients with an initial diagnosis of ameloblastoma, as well as recurrences or metastasized ameloblastoma were treated. Indications cover neoadjuvant therapy up to the use in metastasized patients in an irresectable state. Results ranging from "only" tumor size reduction to restitutio ad integrum.
CONCLUSION
We see the use of BRAF Inhibitors to reduce tumor size with consecutive surgical treatment as a reasonable option for therapy. However, we are aware that at present the data are based only on case reports with the longest follow-up of just 38 months. We encourage further clinical trials in the use of BRAF Inhibitors for selecting ameloblastoma patients in a multi-center setting.
Topics: Male; Humans; Female; Child; Vemurafenib; Proto-Oncogene Proteins B-raf; Ameloblastoma; Imidazoles; Protein Kinase Inhibitors; Mutation; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37115331
DOI: 10.1007/s12032-023-01993-z -
Journal of Cutaneous Pathology Apr 2021Secondary angiosarcoma (AS) most commonly follows breast cancer and includes postirradiation AS (PRAS) and lymphedema-associated AS. The frequent amplification of MYC...
MYC gene amplification by fluorescence in situ hybridization and MYC protein expression by immunohistochemistry in the diagnosis of cutaneous angiosarcoma: Systematic review and appropriate use criteria.
BACKGROUND
Secondary angiosarcoma (AS) most commonly follows breast cancer and includes postirradiation AS (PRAS) and lymphedema-associated AS. The frequent amplification of MYC (8q24.21) in secondary AS and the rising incidence of PRAS and atypical vascular lesions (AVLs) have prompted interest in the diagnostic and prognostic utility of MYC in AS.
METHODS
Retrospective series with ≥2 cases of cutaneous AS and describing the use of fluorescence in situ hybridization (FISH) for MYC amplification or immunohistochemistry (IHC) for MYC overexpression were included.
RESULTS
Sixteen studies met inclusion criteria. Overall, 93% of cases evaluated by FISH and IHC were concordant. The sensitivity of FISH in primary AS was only 6.8%, and protein overexpression occurred without amplification in sun-damaged skin. FISH and IHC were over 78% sensitive in secondary AS but negative in over 98% of AVLs. MYC amplification and FLT4 coamplification were associated with shorter overall survival in secondary AS.
CONCLUSION
FISH for MYC amplification and IHC for MYC overexpression are useful in distinguishing PRAS from AVLs and may also have prognostic value in secondary AS. In contrast, these methods have little diagnostic or prognostic value in primary AS and should not be used to distinguish primary AS from benign vascular neoplasms.
Topics: Aged; Aged, 80 and over; Breast Neoplasms; Female; Gene Amplification; Hemangiosarcoma; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lymphedema; Neoplasms, Radiation-Induced; Prognosis; Proto-Oncogene Proteins c-myc; Retrospective Studies; Sensitivity and Specificity; Skin Neoplasms
PubMed: 33128474
DOI: 10.1111/cup.13912 -
Journal of Gastrointestinal and Liver... Jun 2020The coexistence of RAS and BRAF mutations is extremely rare, occurring in approximately 0.05% of patients with metastatic colorectal cancer (mCRC). Starting from a case...
BACKGROUND AND AIMS
The coexistence of RAS and BRAF mutations is extremely rare, occurring in approximately 0.05% of patients with metastatic colorectal cancer (mCRC). Starting from a case presentation, this review aims to examine the prevalence, clinical, histopathological and molecular features of tumors with concomitant mutations.
METHODS
Case report and systematic review. We performed a systematic literature search in PubMed and EMBASE using the following MeSH terms: "coexistence" OR "concomitant" AND "RAS" AND "BRAF" AND "colorectal cancer" from the inception of the databases onwards.
RESULTS
We present the case of a 53-year-old man diagnosed with metastatic rectal adenocarcinoma with both a KRAS and a BRAF mutation. The review included eleven papers reporting on a total of 30 mCRC cases with concomitant RAS and BRAF mutations. The male/female ratio was 11/5. The average age was 58.5 years. The tumor was located in nine cases on the right colon and in two cases in the left colon. 43.3% of subjects had liver metastases, and 6.6% had lung metastases. Next-generation sequencing (NGS) was used in 36.6% of cases and polymerase chain reaction (PCR) in 16.6% of cases. KRAS mutations were present in 83.3% of patients and NRAS mutations in 16.6% of patients. Survival could be assessed in 10 patients and the median was 21.1 months (about 30% lower than the survival in the general mCRC population).
CONCLUSION
The results of this systematic review suggest the need to design a cohort study (either prospective or retrospective) to better characterize the patients with concomitant RAS and BRAF mutations and to establish the optimal treatment for this rare situation.
Topics: Adenocarcinoma; Antineoplastic Protocols; Colorectal Neoplasms; Female; GTP Phosphohydrolases; High-Throughput Nucleotide Sequencing; Humans; Liver Neoplasms; Lung Neoplasms; Male; Membrane Proteins; Middle Aged; Mutation; Neoplasm Metastasis; Neoplasm Staging; Pharmacogenomic Testing; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Rectal Neoplasms; Rectum; Response Evaluation Criteria in Solid Tumors; Survival Analysis
PubMed: 32530992
DOI: 10.15403/jgld-1003 -
Interventional Neuroradiology : Journal... Aug 2021Somatic KRAS mutations have been identified in the majority of brain arteriovenous malformations (AVM) specimens. The aim of our study was to evaluate the prevalence of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Somatic KRAS mutations have been identified in the majority of brain arteriovenous malformations (AVM) specimens. The aim of our study was to evaluate the prevalence of Kirsten rat sarcoma (KRAS)/murine sarcoma viral oncogene homolog B1 (BRAF) mutations in brain AVM.
METHODS
A systematic literature review was performed in November 2019. We reviewed MEDLINE/PubMed, Cochrane Library, and ClinicalTrials.gov for citation or ongoing trials from January 2010 to March 2020.
RESULTS
6 studies were identified as meeting the inclusion criteria of this review. The total frequency of KRAS mutations in 1726 patients with AVM was 55%. The prevalence of BRAF mutation was 7.5%. The prevalence of AVMs with grade 2 was the most (39%). Frontal and parietal lobes were the commonest sites of AVMs (21%). the most prevalent presentation of patients with AVM was hemorrhage (62%).
CONCLUSION
Our findings support a high prevalence of somatic activating mutations in KRAS and less commonly, BRAF in the overwhelming majority of brain AVMs. Practically and importantly, this pathway homogeneity in CNS arteriovenous malformations also supports the development of targeted therapies with RAS/RAF pathway inhibitors. However, more studies are needed to confirm this hypothesis.
Topics: Animals; Arteriovenous Malformations; Brain; Humans; Mice; Mutation; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 33401991
DOI: 10.1177/1591019920982810 -
BMC Cancer Jul 2020Between 30 and 50% of colon tumors have mutations in the Kirsten-ras (KRAS) gene, which have a large nutritional attributable risk. Despite its high frequency in...
BACKGROUND
Between 30 and 50% of colon tumors have mutations in the Kirsten-ras (KRAS) gene, which have a large nutritional attributable risk. Despite its high frequency in colorectal cancer (CRC), data to support specific associations between KRAS mutations in CRC and diet are sparse. Here, we conducted a systematic review to summarize the current epidemiological evidence on the association between various dietary factors and KRAS mutations.
METHODS
PubMed, Science Direct, and Cochrane databases were searched for relevant studies published until December 31, 2019, using inclusion and exclusion criteria in accordance with PRISMA guidelines. We analyzed the studies to find associations between nutritional factors and CRC tumors with KRAS mutations in humans.
RESULTS
We identified 28 relevant studies to include in this systematic review. In-depth analyses showed unclear associations between nutritional factors and KRAS mutations in CRC. Most epidemiological studies in the same nutrient or food often reported conflicting and/or inconclusive findings, whereas for some dietary factors, the results were homogeneous.
CONCLUSIONS
Further research using a more robust prospective cohort study is needed to lend more credence to the epidemiological associations found between KRAS mutations and dietary factors.
Topics: Acrylamide; Beverages; Colorectal Neoplasms; Dairy Products; Diet; Dietary Fats; Dietary Fiber; Dietary Proteins; Food; Fruit; Genes, ras; Humans; Mutation; Nutrients; Vegetables
PubMed: 32723394
DOI: 10.1186/s12885-020-07189-2 -
Cells Mar 2024We aimed to review the molecular characteristics of metastatic melanoma and the role of surgery in metastasectomy for metastatic melanoma. We performed a systematic... (Review)
Review
We aimed to review the molecular characteristics of metastatic melanoma and the role of surgery in metastasectomy for metastatic melanoma. We performed a systematic literature search on PubMed to identify relevant studies focusing on several mutations, including NRAS, BRAF, NF1, MITF, PTEN, TP53, CDKN2A, TERT, TMB, EGFR, and c-KIT. This was performed in the context of metastatic melanoma and the role of metastasectomy in the metastatic melanoma population. A comprehensive review of these molecular characteristics is presented with a focus on their prognosis and role in surgical metastasectomy.
Topics: Humans; GTP Phosphohydrolases; Melanoma; Membrane Proteins; Proto-Oncogene Proteins B-raf; Skin Neoplasms
PubMed: 38534309
DOI: 10.3390/cells13060465