Analysis of BRAF mutations in circulating tumor cells selected by size from patients with melanoma and comparision to the primary tumor.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21014-e21014
Author(s):  
Janine Wechsler ◽  
Naoual Benali-Furet ◽  
Fei Ye ◽  
Marie-Françoise Avril ◽  
Francoise Boitier ◽  
...  
Keyword(s):  
Primary Tumour ◽  
Primary Melanoma ◽  
Melanoma Cells ◽  
Molecular Target ◽  
Tumour Cells ◽  
Benign Lesions ◽  
Braf Mutations ◽  
Tumour Removal ◽  
Healthy Donors ◽  
The Mean

e21014 Background: The efficacy of anti-BRAF therapies in patients with melanoma has emphasized the need to identify BRAF mutations in the tumour. As circulating tumour cells (CTC) derive from the primary tumour (PT), their analysis may represent a non-invasive tool to follow the molecular-target in blood after tumour removal. Methods: This prospective study included 26 patients: 24 patients had confirmed melanoma, 2 patients had benign lesions (1 naevus and 1 pyogenic granuloma). Blood samples were taken at time of the PT surgical excision; 12 healthy donors were included as controls. The 24 patients, 13 females and 11 males, had invasive melanoma (13 superficial spreading melanoma, 7 nodular melanoma, 1 lentigo malignant melanoma, 1 desmoplastic melanoma, 2 unclassified melanoma.). The mean thickness was 7.8 mm. Cytology, immunophenotyping and analysis of BRAF mutations on exon 15 were performed comparatively in primary tumour and CTC from the same patient. CTC were selected by the ScreenCell method, a single-use innovative system to isolate rare tumour cells through a filter-membrane on the basis of their size. Nucleic acids DNA/RNA were extracted from live CTC after filtration. Results: Isolated CTC and microemboli were found in 21/24 patients and were found comparable to the primary melanoma cells. No CTC was found in 10 healthy donors and 2 patients with benign lesions. The mean number of CTC was 2 CTC per ml, the maximum was 4 CTC and 7 microemboli per ml. Malignancy of CTC was assessed on classic criteria: cell size larger than 15 microns, nucleo-cytoplasmic ratio > 0.5, presence of clusters composed of pleomorphic cells. CTC were positively immunostained either by S-100 or MART1/melanA or HMB45 antibodies; 4 patients were studied for BRAF mutations in both melanoma and CTC. The results (2 negative and 2 positive) were concordant in primary melanoma cells and CTC. The V600E-BRAF mutation was found in the 2 positive cases. Conclusions: The ScreenCell method of CTC selection by size allows to detect BRAF mutations in CTC of patients with melanoma. This simple method could be proposed to follow the molecular-target during the course of evolution and treatment after tumour removal.

scholarly journals Apparent diffusion coefficient for differentiating between benign and malignant hepatic focal lesions

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sherif Abugamra ◽  
Aya Yassin ◽  
Asmaa Saber Mostafa Abdel-Rehim ◽  
Dina Sayed Sheha
Keyword(s):  
Hepatocellular Carcinoma ◽  
Diffusion Coefficient ◽  
Apparent Diffusion Coefficient ◽  
Focal Lesion ◽  
Benign Lesions ◽  
Focal Lesions ◽  
Significant Difference ◽  
Apparent Diffusion ◽  
Malignant Lesions ◽  
The Mean

Abstract Background The aim of this study was to prospectively evaluate the role of diffusion weight MRI (DWI) in the characterization of hepatic focal lesions by using apparent diffusion coefficient (ADC). Thirty patients (18 women, 12 men; mean age 48.5 years) with hepatic focal lesions were included in this study. Patients underwent DW MR imaging with the SPLICE sequence. ADC of each focal lesion carcinoma was calculated from DW MR Images obtained with low and high b values. ADCs were compared among pathological types of focal lesions. Results Among the 30 patients included in the study, 46 focal lesions were detected. Twenty-four lesions were metastatic lesions from primary cancer, 7 lesions were hepatocellular carcinoma (HCC), 9 lesions were hemangiomas, and 6 lesions were simple cysts. There was highly significant difference between the mean ADC of the malignant lesions (metastasis and HCC) and the mean ADC of benign lesions (hemangiomas and cysts). The ADC of malignant lesion was much less than that of benign lesion. The mean ADC of malignant lesions (n = 31) was 0.73 ± 0.19 × 10−3 mm2/s, and the mean ADC of benign lesions (n = 15) was 1.94 ± 0.68 × 10−3 mm2/s (p value < 0.001). There was no significant difference between the cysts and hemangiomas. There was no statistically significant difference between the metastases and hepatocellular carcinoma. Conclusion ADCs values were able to differentiate benign from malignant lesions. ADC should be considered in the work up of patients with hepatic focal lesions.

SENSITIVE AND SPECIFIC ENZYME-LINKED IMMUNOSORBENT ASSAY FOR UROKINASE-TYPE PLASMINOGEN ACTIVATOR IN HUMAN PLASMA

1987 ◽  
Author(s):  
J Grøndahl-HANSEN ◽  
N Agerlin ◽  
L S Nielsen ◽  
K Danø
Keyword(s):  
Plasminogen Activator ◽  
Immunosorbent Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mean Values ◽  
Amino Terminal ◽  
Type Plasminogen Activator ◽  
Healthy Donors ◽  
Urokinase Type Plasminogen Activator ◽  
The Mean

An enzyme-linked immunosorbent assay (ELISA) was developed for the measurement of human urokinase-type plasminogen activator (u-PA) in plasma and serum. Microtiter plates were coated with a monoclonal antibody and incubated with standard or sample. Bound u-PA was quantitated with polyclonal antibodies conjugated with biotin, followed by avidin-peroxidase. The assay was 10-fold as sensitive as other previously reported ELISAs, the detection limit being approximately 1 pg of u-PA in a volume of 100 μl with a linear dose-response up to 15 pg of u-PA. The assay detected active u-PA and its inactive proenzyme form equally well and the recovery of both forms was higher than 90% in plasma. A variety of structurally related proteins, including t-PA, were tested, but no reaction with proteins other than u-PA and its amino-terminal degradation product were observed. The intra-assay and inter-assay coefficients of variation for determination of u-PA in plasma were 7.6% and 8.4%, respectively. The assay was equally applicable to serum. The values obtained with plasma and serum were similar, and the results were not affected by small variations in the preparation of the samples. The ELISA was used to measure the concentration of u-PA in plasma from 34 healthy donors. The mean values for u-PA in plasma from healthy donors was 1.1 ng/ml ± 0.3 ng/ml (SD) (range 0.6 - 1.5 ng/ml). No significant differences were found between men and women and no correlation between u-PA concentration and age could be demonstrated.The mean u-PA concentration in plasma from healthy donors obtained in this study is substantially lower than that reported by others. This might be due to different methods of determination of the protein content of the standard preparations or to differences in the specificity of the assays.

scholarly journals Polyclonality of BRAF mutations in primary melanoma and the selection of mutant alleles during progression

2011 ◽  
Vol 104 (3) ◽  
pp. 464-468 ◽  
Author(s):  
J Lin ◽  
Y Goto ◽  
H Murata ◽  
K Sakaizawa ◽  
A Uchiyama ◽  
...  
Keyword(s):  
Primary Melanoma ◽  
Braf Mutations ◽  
Selection Of

Prognostic value of proliferation, PD-L1 and nuclear size in patients with superior sulcus tumours treated with chemoradiotherapy and surgery

2021 ◽  
pp. jclinpath-2021-207570
Author(s):  
Hans Blaauwgeers ◽  
Birgit I Lissenberg-Witte ◽  
Chris Dickhoff ◽  
Sylvia Duin ◽  
Erik Thunnissen
Keyword(s):  
Overall Survival ◽  
Proliferative Activity ◽  
Tumour Cells ◽  
Nuclear Size ◽  
Residual Tumour ◽  
Trimodality Therapy ◽  
Median Difference ◽  
The Mean ◽  
Superior Sulcus ◽  
Mib 1

AimsThe aim of this study was to determine the relationship between proliferative activity, PD-L1 status and nuclear size changes after preoperative chemoradiotherapy (CRT) and the clinical outcome in patients with superior sulcus tumours.MethodsProliferative activity (MIB-1) and PD-L1 status were estimated by immunohistochemistry in the tumour cells of resection specimen in a series of 33 patients with residual tumour after trimodality therapy for a sulcus superior tumour between 2005 and 2014. A morphometric analysis of both pretreatment and post-treatment tumour materials was also performed. Results were related to disease-free survival and overall survival.ResultsLow proliferative activity (<20% MIB-1) was associated with better overall survival: 2-year overall survival of 73% compared with 43% and 25%, respectively, for moderate (MIB-1 20%–50%) and high (MIB-1 >50%) proliferative activity (p=0.016). A negative PD-L1 status (<1% positive tumour cells) was also associated with better overall survival (p=0.021). The mean nuclear size of normal lung tissue pneumocytes was significantly smaller compared with the mean nuclear size of tumour cells of the resection specimens (median difference −38.1; range −115.2 to 16.0; p<0.001). The mean nuclear size of tumour cells did not differ between pretreatment biopsies and resection specimens (median difference −4.6; range −75.2 to 86.7; p=0.14). Nuclear size was not associated with survival (p=0.82).ConclusionsLow proliferative activity determined by MIB-1 as well as a negative PD-L1 expression are significantly associated with better overall survival in patients with residual tumour after CRT for superior sulcus tumour.

scholarly journals 68Ga-DOTA-GGNle-CycMSHhextargets the melanocortin-1 receptor for melanoma imaging

2018 ◽  
Vol 10 (466) ◽  
pp. eaau4445 ◽  
Author(s):  
Jianquan Yang ◽  
Jingli Xu ◽  
Rene Gonzalez ◽  
Thomas Lindner ◽  
Clemens Kratochwil ◽  
...  
Keyword(s):  
Melanoma Cells ◽  
Molecular Target ◽  
Therapeutic Agents ◽  
Human Melanoma ◽  
Emission Tomography ◽  
Melanocortin 1 Receptor ◽  
Imaging Probe ◽  
Specific Targeting ◽  
Human Melanoma Cells ◽  
Positron Emission

Melanocortin-1 receptor (MC1R) is a molecular target for melanoma imaging and therapy because of its overexpression on rodent and human melanoma cells. Here, we evaluated the MC1R targeting and specificity of68Ga-DOTA-GGNle-CycMSHhexand Cy5.5-GGNle-CycMSHhexusing murine and human melanoma cells, and murine and xenografted tumors.68Ga-DOTA-GGNle-CycMSHhexwas used first in human as an imaging probe to evaluate the possibility of radionuclide therapy in patients with advanced-stage melanoma.68Ga-DOTA-GGNle-CycMSHhexand Cy5.5-GGNle-CycMSHhexdisplayed MC1R-specific targeting properties in murine and human melanoma cells, as well as in murine melanoma and human melanoma–xenografted tumors. Both B16/F10 and M21 melanoma lesions could be easily imaged by positron emission tomography using68Ga-DOTA-GGNle-CycMSHhex. The first-in-human images of melanoma brain metastases in patients demonstrated the clinical relevance of MC1R as a molecular target for melanoma imaging, highlighting the potential of68Ga-DOTA-GGNle-CycMSHhexas an MC1R-targeting melanoma imaging probe and underscoring the need to develop MC1R-targeting therapeutic agents for treating patients with metastatic melanoma.

scholarly journals Clinical profile of cardiac myxoma: 11 years’ experience of 90 cases

2016 ◽  
Vol 31 (1) ◽  
pp. 18-22
Author(s):  
Md Toufiqur Rahman ◽  
Md Zulfikar Ali ◽  
Md Humayun Kabir ◽  
STM Abu Azam ◽  
AAS Majumder ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Primary Tumour ◽  
Correct Diagnosis ◽  
Cardiac Myxoma ◽  
Benign Neoplasm ◽  
Clinical Feature ◽  
Duration Of Symptoms ◽  
Pedal Oedema ◽  
Mechanical Interference ◽  
The Mean

Introduction: Cardiac myxoma is a benign neoplasm that represents the most common primary tumour of the heart. Because of nonspecific symptoms, early diagnosis may be a challenge. Although the left atrium is the most commonly involved site of origin in 75% of cases, it can arise from any of the cardiac chambers. Symptoms from a cardiac myxoma are more pronounced when the myxomas are left-sided, racemosus, and over 5 cm in diameter. Symptoms are produced by mechanical interference with cardiac function or embolization. Being intravascular and friable, myxomas account for most cases of tumor embolism. The site of embolism is dependent upon the location (left or right atrium) and the presence of an intracardiac shunt. Most atrial myxomas are benign and can be removed by surgical resection.Objectives: To see clinical presentation and echocardiographic profile of cardiac myoxomas.Methods: 90 cardiac myxoma patients who admitted both in cardiology and cardiac surgery departments of National Institute of Cardiovascular Diseases (NICVD), Dhaka from August 2003 to July, 2014 were studied clinically and by echocardiogram. Clinical histories were reviewed, noting age, gender, and clinical presentation.Results: There were 30 males and 60 females, ages ranged from 17 to 76 years. The commonest clinical feature was dyspnoea (94.44%), followed by palpitation (76.67%), chest discomfort (74.44%), constitutional symptoms (50%), pedal oedema (20%), syncope (14.44%), and embolization (7.7%). The mean duration of symptoms was 09.7 months.Conclusion: The clinical presentation of cardiac myxoma is often nonspecific, so high index of clinical suspicion is important for its early and correct diagnosis. The size and appearance of the myxomas correlated with the presenting symptoms.Bangladesh Heart Journal 2016; 31(1) : 18-22

scholarly journals Clinico–pathological study of hysterectomy in benign lesions: a study of 379 hysterectomies

2017 ◽  
Vol 6 (3) ◽  
pp. 934
Author(s):  
Dharmendra Singh Fathepuriya ◽  
Leena Verma ◽  
Seema Sharma
Keyword(s):  
Vaginal Hysterectomy ◽  
Uterine Prolapse ◽  
Randomized Study ◽  
Abdominal Hysterectomy ◽  
Reproductive Organ ◽  
Benign Lesions ◽  
Pathological Study ◽  
Dysfunctional Uterine Bleeding ◽  
Related Symptom ◽  
The Mean

Background: Uterus is a very vital reproductive organ and is subjected to many benign and malignant diseases. Hysterectomy is one of the most frequently performed procedures all over the world. Aims and Objectives of the work was to study the clinical benign indications of hysterectomy specimens and to correlate the findings with the histopathological reports.Methods: A prospective and randomized study was performed in 379 cases of elective hysterectomies for benign lesions.Results: Abdominal hysterectomy was performed in 64.6% cases while vaginal hysterectomy accounted for 35.3% cases. The mean age for hysterectomy was 45 years with a range from 14 to 78 years. Patients mostly presented with menstrual irregularities (34.3%) followed by prolapse uterus (30%). The principle indication of elective hysterectomy was leiomyoma and was present in 197(51.9%) patients, followed by prolapse uterus in 134 (35.3%) and dysfunctional uterine bleeding (DUB) in 26 (6.8%) patients. Maximum numbers of cases of leiomyoma, uterine prolapse and DUB were found in age group of 41-50 yrs.Conclusions: The number of abdominal hysterectomy was more than vaginal hysterectomy. Most common presenting feature was menstrual related symptom followed by prolapsed. The main indication for elective hysterectomy was leiomyoma, prolapsed and DUB.

scholarly journals Innovator Filgrastim versus Generic Filgrastim in Hematopoietic Stem Cell Transplantation Mobilization

2021 ◽  
Author(s):  
Sadik Husian ◽  
Preethi Jeyaraman ◽  
S. K. Gupta ◽  
Reeta Rai ◽  
Sangeeta Pathak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Healthy Donors ◽  
The Mean ◽  
Mean Time ◽  
Autologous Hsct

Abstract Methods This is a retrospective study. G-CSF was administered in the dose of 10 μg/kg subcutaneous as a single dose for 4 days. On day 5, peripheral blood stem cell (PBSC) apheresis was performed using Haemonetics MCS plus or COBE Spectra apheresis machine through a double-lumen central venous catheter. Primary outcome parameters were the total number of CD34+ HSCs/kg of recipient weight mobilized in peripheral blood and the number of days required for neutrophil and platelets engraftment, respectively. Objective We compared the effectiveness and safety of innovator filgrastim versus generic filgrastim in patients who underwent hematopoietic stem cell transplantation (HSCT). Results A total of 91 stem cell mobilizations was analyzed. There were 58 normal healthy donors for allogeneic HSCT and 33 patients for autologous HSCT. There was no statistically significant difference among groups in terms of total collected CD34+ cells value (p = 0.609). The mean time to neutrophil engraftment was 13.7 days in the innovator group and 13.2 days in the Grafeel group (p = 0.518). The mean time to platelet engraftment was 16.2 days in the innovator group and 14.8 days in the generic group (p = 0.435). The patient who received generic filgrastim had more febrile episodes during the course of transplantation (p = 0.020). Conclusion Generic filgrastim was found to be comparable to original filgrastim for peripheral blood stem cell mobilization in normal healthy donors for allogeneic HSCT and patients for autologous HSCT.

scholarly journals Concomitant BCORL1 and BRAF Mutations in Vemurafenib-Resistant Melanoma Cells

Neoplasia ◽  
2018 ◽  
Vol 20 (5) ◽  
pp. 467-477 ◽  
Author(s):  
Luca Mologni ◽  
Mariantonia Costanza ◽  
Geeta Geeta Sharma ◽  
Michela Viltadi ◽  
Luca Massimino ◽  
...  
Keyword(s):  
Melanoma Cells ◽  
Braf Mutations
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