scholarly journals Into the Unknown-exploring a Rare BRAF K601E Mutation in a Rectal Adenocarcinoma

2020 ◽  
pp. 224-228
Author(s):  
Nupur Karnik ◽  
Mandar Ankolkar ◽  
Prachi Gogte ◽  
Mukta Ramadwar ◽  
Vikas Ostwal ◽  
...  
Keyword(s):  
Rectal Adenocarcinoma ◽  
Gene Mutations ◽  
Braf V600e ◽  
Biological Behavior ◽  
Peritoneal Disease ◽  
Case Presentation ◽  
Therapeutic Mechanisms ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

Aim: v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene mutations are broadly divided as BRAF V600E and BRAF non-V600E. These groups exhibit differences in the clinical, histological, molecular and therapeutic mechanisms. Case Presentation and Discussion: The case described is of a middle aged female with an aggressive rectal adenocarcinoma diagnosed on biopsy and immunohistochemistry. A rare BRAF non-V600E mutation at codon 601, K601E was detected. This mutation has been described in very few cases of colonic adenocarcinoma. The tumor showed extensive local and peritoneal disease with lung metastasis at presentation and progression on the primary line of chemotherapy. The aggressive predisposition of the tumor was contrary to reports suggesting non-V600E tumors to connote a better prognosis. Conclusion: Active reporting of non-V600E BRAF variants in colorectal adenocarcinoma is essential in order to create a robust database which will help in assessing a biological behavior of these tumors and explore the role of targeted therapy.

scholarly journals Necessity of Microdissecting Different Tumor Components in Pulmonary Tumor Pyrosequencing

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Dahui Qin ◽  
Zhong Zheng ◽  
Shanxiang Shen ◽  
Prudence Smith ◽  
Farah K. Khalil
Keyword(s):  
Gene Mutations ◽  
Molecular Testing ◽  
Tissue Sampling ◽  
Wild Type ◽  
Kras Mutations ◽  
Viral Oncogene ◽  
Pulmonary Tumor ◽  
New Challenges ◽  
Murine Sarcoma ◽  
Viral Oncogene Homolog

Microdissection is a useful method in tissue sampling prior to molecular testing. Tumor heterogeneity imposes new challenges for tissue sampling. Different microdissecting methods have been employed in face of such challenge. We improved our microdissection method by separately microdissecting the morphologically different tumor components. This improvement helped the pyrosequencing data analysis of two specimens. One specimen consisted of both adenocarcinoma and neuroendocrine components. When both tumor components were sequenced together for KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutations, the resulting pyrogram indicated that it was not a wild type, suggesting that it contained KRAS mutation. However, the pyrogram did not match any KRAS mutations and a conclusion could not be reached. After microdissecting and testing the adenocarcinoma and neuroendocrine components separately, it was found that the adenocarcinoma was positive for KRAS G12C mutation and the neuroendocrine component was positive for KRAS G12D mutation. The second specimen consisted of two morphologically different tumor nodules. When microdissected and sequenced separately, one nodule was positive for BRAF (v-raf murine sarcoma viral oncogene homolog B1) V600E and the other nodule was wild type at the BRAF codon 600. These examples demonstrate that it is necessary to microdissect morphologically different tumor components for pyrosequencing.

scholarly journals Cerebral astroblastoma with oligodendroglial-like cells：A case report

2020 ◽  
Author(s):  
Jian Gu ◽  
Juan-Han Yu ◽  
Hongtao Xu ◽  
Qingchang Li ◽  
Xueshan Qiu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Gene Mutations ◽  
Visual Disturbance ◽  
Biological Behavior ◽  
Left Temporal Lobe ◽  
Ki 67 ◽  
Case Presentation ◽  
Negative Results ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri

Abstract Background: Astroblastoma is a rare tumor of the central nervous system, with unclear biological behavior and origin. Its histopathological features have been well established. However, to the best of our knowledge, astroblastoma with oligodendroglial-like cells have not been reported. Case presentation: Herein, we reported a case of astroblastoma with atypical pathological features. A 15-year-old girl presented with nausea, vomiting, headache and visual disturbance. Magnetic resonance imaging (MRI) revealed a large neoplasm in the left temporal lobe. Histologically, the tumor showed solid and pseudopapillary structure. The tumor cells were radially arranged around blood vessels, with a single, prominent process, and as astroblastic pseudorosettes. More importantly, typical oligodendroglial-like cells were observed. In addition to membrane staining for EMA, immunohistochemical staining also showed that the tumor cells were positive for GFAP and Vimentin. The oligodendroglial-like cells were positive for GFAP, Vimentin, and Olig-2. The Ki-67 labeling index was about 4%. Sequencing for IDH1 codon 132 and IDH2 codon 172 gene mutations showed negative results. Furthermore, fluorescent analysis revealed neither 1p nor 19q deletion in the lesion. Based on these findings, the tumor was finally diagnosed as astroblastoma. Conclusions: Herein, we reported an extremely rare case of astroblastoma, which was morphologically characterized by the appearance of oligodendroglial-like cells.

Role of FLT3 gene mutations in acute myeloid leukemia: effect on course of disease and results of therapy

2019 ◽  
Vol XIV (1) ◽  
Author(s):  
A.M. Radzhabova ◽  
S.V. Voloshin ◽  
I.S. Martynkevich ◽  
A.A. Kuzyaeva ◽  
V.A. Shuvaev ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Course Of Disease ◽  
Acute Myeloid

Beyond Promoter: The Role of Macrophage in Invasion and Progression of Renal Cell Carcinoma

2020 ◽  
Vol 15 (7) ◽  
pp. 588-596
Author(s):  
Haibao Zhang ◽  
Guodong Zhu
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Formation ◽  
Biological Behavior ◽  
Tumor Stem Cell ◽  
The Past ◽  
The Common

Renal cell carcinoma (RCC) is one of the common urologic neoplasms, and its incidence has been increasing over the past several decades; however, its pathogenesis is still unknown up to now. Recent studies have found that in addition to tumor cells, other cells in the tumor microenvironment also affect the biological behavior of the tumor. Among them, macrophages exist in a large amount in tumor microenvironment, and they are generally considered to play a key role in promoting tumorigenesis. Therefore, we summarized the recent researches on macrophage in the invasiveness and progression of RCC in latest years, and we also introduced and discussed many studies about macrophage in RCC to promote angiogenesis by changing tumor microenvironment and inhibit immune response in order to activate tumor progression. Moreover, macrophage interactes with various cytokines to promote tumor proliferation, invasion and metastasis, and it also promotes tumor stem cell formation and induces drug resistance in the progression of RCC. The highlight of this review is to make a summary of the roles of macrophage in the invasion and progression of RCC; at the same time to raise some potential and possible targets for future RCC therapy.

scholarly journals Genetic and epigenetic mechanisms in the development of congenital heart diseases

2021 ◽  
Vol 4 (2) ◽  
pp. e000196
Author(s):  
Yue Wu ◽  
Xiaosi Jin ◽  
Yuhao Zhang ◽  
Jing Zheng ◽  
Rulai Yang
Keyword(s):  
Congenital Heart ◽  
Heart Diseases ◽  
Gene Mutations ◽  
Morbidity And Mortality ◽  
Molecular Medicine ◽  
Epigenetic Mechanisms ◽  
Epigenetic Factors ◽  
Near Future

Congenital heart disease (CHD) is the most common of congenital cardiovascular malformations associated with birth defects, and it results in significant morbidity and mortality worldwide. The classification of CHD is still elusive owing to the complex pathogenesis of CHD. Advances in molecular medicine have revealed the genetic basis of some heart anomalies. Genes associated with CHD might be modulated by various epigenetic factors. Thus, the genetic and epigenetic factors are gradually accepted as important triggers in the pathogenesis of CHD. However, few literatures have comprehensively elaborated the genetic and epigenetic mechanisms of CHD. This review focuses on the etiology of CHD from genetics and epigenetics to discuss the role of these factors in the development of CHD. The interactions between genetic and epigenetic in the pathogenesis of CHD are also elaborated. Chromosome abnormalities and gene mutations in genetics, and DNA methylations, histone modifications and on-coding RNAs in epigenetics are summarized in detail. We hope the summative knowledge of these etiologies may be useful for improved diagnosis and further elucidation of CHD so that morbidity and mortality of children with CHD can be reduced in the near future.

scholarly journals COVID-19 related mortality in post-operative cardiac surgical patients

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Azhar Hussain ◽  
Amina Khalil ◽  
Priyanka Kolvekar ◽  
Prity Gupta ◽  
Shyamsunder Kolvekar
Keyword(s):  
Cardiac Surgery ◽  
Long Term Outcomes ◽  
Case Presentation ◽  
Elective Cardiac Surgery ◽  
The United Kingdom ◽  
Global Pandemic ◽  
Cardiac Operations ◽  
Related Mortality

Abstract Background COVID-19 has caused a global pandemic of unprecedented proportions. Elective cardiac surgery has been universally postponed with only urgent and emergency cardiac operations being performed. The National Health Service in the United Kingdom introduced national measures to conserve intensive care beds and significantly limit elective activity shortly after lockdown. Case presentation We report two cases of early post-operative mortality secondary to COVID-19 infection immediately prior to the implementation of these widespread measures. Conclusion The role of cardiac surgery in the presence of COVID-19 is still very unpredictable and further studies on both short term and long term outcomes are warranted.

scholarly journals 466 Resection or Enucleation for Extremely Giant Hepatic Haemangiomata? A Case Report and Review of The Literature

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
R E Fraser ◽  
G R Layton ◽  
L L Kuan ◽  
A R Dennison
Keyword(s):  
Expectant Management ◽  
Evidence Base ◽  
Primary Treatment ◽  
Cavernous Haemangioma ◽  
Liver Tumours ◽  
Case Presentation ◽  
Best Management ◽  
Anatomical Liver Resection ◽  
Benign Liver

Abstract Background Cavernous hepatic haemangiomas are benign liver tumours and although common when small, giant haemangiomas (usually accepted as being greater than 10cm) are infrequent. Treatment is indicated in patients who are symptomatic or if diagnosis is unclear, although with giant haemangiomas, many support expectant management of asymptomatic lesions due to the risk of major complications. Traditionally hepatic resection has been the primary treatment option for these lesions, but a variety of other techniques, including enucleation, have been described as safe and effective alternatives. There remains equipoise in respect of the best management of giant haemangiomas above 10cm. Cases of such size are rare and so there is a paucity of data available. Case presentation We present a case of a 65-year-old male who underwent successful anatomical liver resection for a 5kg giant cavernous haemangioma of 26cm diameter following its incidental identification during an ultrasound scan. We also discuss and compare the role of resection and enucleation for the treatment of haemangiomata greater than 20cm in diameter. Conclusions This case demonstrates successful resection of an unusually giant haemangioma which, in contrast to the majority of literature, provides a valuable addition to the limited evidence base for management of this condition by anatomical resection.

scholarly journals Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma

2021 ◽  
Vol 22 (13) ◽  
pp. 6726
Author(s):  
Agata M. Gaweł ◽  
Maciej Ratajczak ◽  
Ewa Gajda ◽  
Małgorzata Grzanka ◽  
Agnieszka Paziewska ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Endocrine System ◽  
Metastatic Potential ◽  
Multidrug Resistant ◽  
Thyroid Tumor ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Spheroid Formation

Background: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., BRAF V600E mutation) is associated with the activity of FRMD5. Methods: The studies were conducted on TPC1 and BCPAP (BRAF V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of FRMD5. The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the FRMD5 expressional status. Results: The obtained data indicate that the expression of FRMD5 is significantly enhanced in BRAF V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both BRAF-wt and BRAF-mutated PTC cells were observed. It was also found that knockdown of FRMD5 significantly alters the expression of multidrug resistant genes. Conclusions: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.

scholarly journals Osteopontin in Cardiovascular Diseases

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1047
Author(s):  
Kohsuke Shirakawa ◽  
Motoaki Sano
Keyword(s):  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Gene Mutations ◽  
Major Adverse Cardiovascular Event ◽  
Matricellular Protein ◽  
Pathological State ◽  
Adverse Cardiovascular Event ◽  
Anti Inflammatory

Unprecedented advances in secondary prevention have greatly improved the prognosis of cardiovascular diseases (CVDs); however, CVDs remain a leading cause of death globally. These findings suggest the need to reconsider cardiovascular risk and optimal medical therapy. Numerous studies have shown that inflammation, pro-thrombotic factors, and gene mutations are focused not only on cardiovascular residual risk but also as the next therapeutic target for CVDs. Furthermore, recent clinical trials, such as the Canakinumab Anti-inflammatory Thrombosis Outcomes Study trial, showed the possibility of anti-inflammatory therapy for patients with CVDs. Osteopontin (OPN) is a matricellular protein that mediates diverse biological functions and is involved in a number of pathological states in CVDs. OPN has a two-faced phenotype that is dependent on the pathological state. Acute increases in OPN have protective roles, including wound healing, neovascularization, and amelioration of vascular calcification. By contrast, chronic increases in OPN predict poor prognosis of a major adverse cardiovascular event independent of conventional cardiovascular risk factors. Thus, OPN can be a therapeutic target for CVDs but is not clinically available. In this review, we discuss the role of OPN in the development of CVDs and its potential as a therapeutic target.

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