Differences in molecular profiles of males and females with colorectal cancer (CRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 623-623
Author(s):  
Afsaneh Barzi ◽  
Mohamed E. Salem ◽  
Joanne Xiu ◽  
Wolfgang Michael Korn ◽  
John Marshall ◽  
...  
Keyword(s):  
Tumor Location ◽  
Molecular Profile ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Significant Difference ◽  
Number Variation ◽  
Males And Females ◽  
Variation Assessment ◽  
Metastatic Sites ◽  
Next Generation Sequencing Ngs

623 Background: Females (F) have a lower incidence of CRC and carry a better overall prognosis than males(M). We explored the differences in the molecular profile of CRC as an explanation for the differences in the outcome. Methods: CRC cases submitted to Caris Life Sciences from 2015 to 2017 were analyzed. These cases were tested with next generation sequencing (NGS) of 592 genes and a panel of IHC and copy number variation assessment. Microsatellite instability (MSI) was evaluated with NGS for known MSI loci in the target regions. High Tumor mutational load (TML-H) was defined as ≥17 mutations/megabase. Results: Data from a total of 1768 CRC tumors (F: 859; M: 909) was available for analysis. The mean age at testing was similar between the two groups (F 59 vs. M 60 years). Tumor location was unknown in more than 40% of the cases. For those with known tumor location (1056) F had a higher rate in right sided than left sided and rectal tumors (51% vs. 47% vs. 40%, p = 0.006). Overall, F carried significantly lower frequency of mutation in APC (68% vs. 74%, p = 0.02), higher frequency of BRAF (11% vs. 6.6%, p = 0.003) and BRCA1 (2% vs. 0.6%, p = 0.007). PDL1 expression was higher in F (4.5% vs. 2.1%, p = 0.006) and MGMT expression was higher in M (63% vs. 56%, p = 0.04). There was no significant difference in the TML-H (F:6.4% vs. M:5.9%) and MSI-high (F:6.2% in vs M:4.8%). When primary (877) and metastatic tumors (838) were investigated separately, mutations in APC was higher in M primary tumors (74% vs. 68% p = 0.03) while not different in metastatic sites. On the contrary, BRCA1 mutations were higher in the metastatic sites for F (2% vs. 0.2%, p = 0.02). PD-L1 was higher in the primary tumor of F (5.2% vs. 1.8%, p = 0.008) and PD-1 on tumor infiltrating lymphocyte in metastatic tumors in F (48% vs. 30%, p = 0.01). Conclusions: The profile of female patients (higher rates of PDL1 in primary and PD1 in metastatic tumors) supports a higher degree of immune evasion. The differences in the profile of metastatic vs. primary sites may be due to the differences in the mechanism of metastasis in females vs. males and may have implications for PDX models.

scholarly journals Metastasis-associated fibroblasts: an emerging target for metastatic cancer

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Zimu Wang ◽  
Jiaxin Liu ◽  
Hairong Huang ◽  
Mingxiang Ye ◽  
Xinying Li ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Metastatic Cancer ◽  
Antiangiogenic Therapy ◽  
Treatment Strategies ◽  
Therapeutic Strategies ◽  
Therapeutic Resistance ◽  
Metastatic Tumors ◽  
Stromal Fibroblasts ◽  
Primary Tumors ◽  
Metastatic Sites

AbstractMetastasis suggests a poor prognosis for cancer patients, and treatment strategies for metastatic cancer are still very limited. Numerous studies have shown that cancer-associated fibroblasts (CAFs), a large component of the tumor microenvironment, contribute to tumor metastasis. Stromal fibroblasts at metastatic sites are different from CAFs within primary tumors and can be termed metastasis-associated fibroblasts (MAFs), and they also make great contributions to the establishment of metastatic lesions and the therapeutic resistance of metastatic tumors. MAFs are capable of remodeling the extracellular matrix of metastatic tumors, modulating immune cells in the tumor microenvironment, promoting angiogenesis and enhancing malignant tumor phenotypes. Thus, MAFs can help establish premetastatic niches and mediate resistance to therapeutic strategies, including immunotherapy and antiangiogenic therapy. The results of preclinical studies suggest that targeting MAFs can alleviate the progression of metastatic cancer and mitigate therapeutic resistance, indicating that MAFs are a promising target for metastatic cancer. Here, we comprehensively summarize the existing evidence on MAFs and discuss their origins, generation, functions and related therapeutic strategies in an effort to provide a better understanding of MAFs and offer treatment perspectives for metastatic cancer.

Phosphorylated signal transducer and activator of transcription–3 (p-STAT3) expression concordance in paired primary and metastatic colorectal cancers (mCRC): Updated analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15137-e15137
Author(s):  
Daniel Yokom ◽  
E. Celia Marginean ◽  
Derek J. Jonker ◽  
Allen M. Gown ◽  
Shelly Sud ◽  
...  
Keyword(s):  
Survival Rates ◽  
Tissue Microarrays ◽  
Secondary Outcome ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Disease Outcomes ◽  
One Year ◽  
Metastatic Sites ◽  
Transcription 3

e15137 Background: p-STAT3 is a transcription factor which is associated with poor prognosis in multiple cancers. Overexpression of p-STAT3 by immunohistochemistry (IHC) in tumors of patients with mCRC is associated with more aggressive disease and decreased survival. Concordance of p-STAT3 expression in primary and metastatic tumors was assessed to determine the temporal heterogeneity of expression and correlation with clinical outcomes. Methods: Patients with tissue available from both primary and liver metastases were identified retrospectively. Tissue microarrays (TMA) were constructed using 2 x 2mm cores. Nuclear p-STAT3 expression intensity by IHC was graded as absent, low, or high. Primary outcome was concordance of p-STAT3 expression between primary and metastatic sites. Secondary outcome was correlation of p-STAT3 expression with disease outcomes. Results: 91 patients were identified: 55% were male, median age at diagnosis was 63, 60% had left-sided disease and 81% of metastases were synchronous. Expression of p-STAT3 in primary tumors was 23% high, 47% low and absent in 30% compared to 29% high, 50% low, and 21% absent in metastases. Concordant expression was observed in 23% of patients whereas it increased in 46% and decreased in 31% from primary to metastasis. Pearson’s correlation was 0.119 indicating a weak concordance. After a median follow-up of 7 years, 50 of 91 patients died. One-year and 5-year survival rates were 92% and 44% respectively, while the median overall survival (mOS) was 4.7 years [95%CI 3.1-6.4]. No significant prognostic correlation between primary or metastatic p-STAT3 expression and mOS was found. Conclusions: There was low concordance of p-STAT3 expression in primary and metastatic tumors of patients with mCRC. Tumor staining heterogeneity due to sampling of small cores included in TMA and predominance of synchronous metastases may play a role. Further research in the use of p-STAT3 as a biomarker in patients with mCRC is needed.

Mutation analysis of mucosal and cutaneous melanomas during progression.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21047-e21047
Author(s):  
Giuseppe Palmieri ◽  
Maria Colombino ◽  
Milena Casula ◽  
Amelia Lissia ◽  
Gerardo Botti ◽  
...  
Keyword(s):  
Mucosal Melanoma ◽  
Braf Mutations ◽  
Driver Genes ◽  
Primary Tumors ◽  
Paired Samples ◽  
Metastatic Lesions ◽  
Tumor Tissues ◽  
Melanoma Patients ◽  
Metastatic Sites ◽  
Next Generation Sequencing Ngs

e21047 Background: The prevalence of mutations in driver genes during progression in cutaneous and mucosal melanomas remains inconclusive. We investigated the prevalence and distribution of mutations in main candidate genes involved in melanomagenesis among different melanoma tissues using a next-generation sequencing (NGS) approach. Methods: Forty-eight tumor samples from 36 patients with mucosal melanoma (MM) and fifty-two tumor samples from 34 patients with cutaneous melanoma (CM) were collected, after obtaining patients’ written informed consent for tissue sampling. Genomic DNA was isolated from macrodissected tumor tissues containing at least 80% neoplastic cells and analyzed for mutations in 25 most common melanoma-associated oncogenes and tumor suppressor genes, using the IMI Diagnostic Melanoma Panel on the Ion Torrent platform (Life Technologies, USA). Results: A total of 100 tumor tissues from 70 melanoma patients were analyzed. BRAF mutations were detected in 21/34 (62%) CM patients and 13/36 (36%) mm patients. The second most prevalent mutations were found in K-/N-RAS (6/34; 18%) and cKIT (6/36; 17%) genes among CM and mm patients, respectively. No concomitant mutations of BRAF, RAS, and cKIT genes were detected. Among others, mutations were more frequently found in CCND1 (20%), ARID2 (16%), and NF1(12%) genes, considering the entire series of patients. Vast majority of patients who had paired samples of primary and secondary melanomas showed consistent mutation patterns between primary tumors and metastatic lesions. Similar frequencies of mutations in driver genes were seen across metastatic sites. Conclusions: In the era of targeted therapies, assessment of the spectrum and distribution of mutations in main molecular targets among patients with melanoma is needed. Our findings about the prevalence of mutations in driver genes in paired tumor lesions from patients with cutaneous and mucosal melanoma may be useful in the management of such diseases. The Italian Melanoma Intergroup (IMI) includes the following additional members who participated as investigators in this study: Mario Mandalà, Paola Queirolo, Ignazio Stanganelli, Vanna Chiarion Sileni, Pietro Quaglino, Anna Maria Di Giacomo.

PATH-04. LEPTOMENINGEAL DISEASE IN PATIENTS WITH HISTONE-MUTANT GLIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi115-vi115
Author(s):  
Maria Diaz ◽  
Carlos Eduardo Silva Correia ◽  
Andrew Lin ◽  
Alexandra Miller ◽  
Elena Pentsova
Keyword(s):  
Tumor Location ◽  
Molecular Profile ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Tumor Biopsy ◽  
Histone 3 ◽  
Diffuse Gliomas ◽  
Next Generation Sequencing Ngs ◽  
H3 K27m Mutations ◽  
Generation Sequencing

Abstract INTRODUCTION The 2016 WHO classification describes a subtype of midline gliomas harboring histone 3 (H3) K27M mutations, and the upcoming 2021 edition may include a new subtype of hemispheric diffuse gliomas with H3 G34R/V mutations. Since we began to perform molecular profiling at Memorial Sloan Kettering Cancer Center (MSKCC) we have observed an increased prevalence of leptomeningeal disease (LMD) in this population. However, the incidence and clinical behavior of LMD has not been well defined. METHODS This is a retrospective study of patients with H3-mutant gliomas at MSKCC diagnosed from 01/2012 to 02/2021, either by tumor biopsy or by cerebrospinal fluid (CSF). Histone mutations were identified through next-generation sequencing (NGS). RESULTS We found 40 patients (pts) harboring H3 mutations (K27M mutations in 31 pts, G34R/V in 8, and both in one), with 2/40 (5%) mutations identified through CSF NGS only and rest in tumor tissue. Median age was 20.5 years (4-70); 25 were male. Tumor location was midline for K27M-mutant tumors (thalamus [N=15], brainstem [N=10], spine [N=5], pineal gland [N=1]) and hemispheric for G34R/V-mutant tumors; tumor with both mutations was thalamic. LMD was diagnosed in 22/40 (55%) pts radiographically, including 19/31 (61%) of K27M-mutant pts and 3/8 (38%) of G34R/V-mutant pts (patient with both mutations did not develop LMD). At analysis, 10 patients remain alive. Median time from diagnosis to LMD was 8.8 months (0-44.4), with median OS of 6.5 months (0.3-34) after LMD diagnosis. CONCLUSION More than half of patients with histone-mutant gliomas develop LMD, including over a third of patients with G34R/V mutations. Neuroaxis imaging should be performed in conjunction with CSF studies in histone-mutant gliomas. Besides, CSF NGS represents an important tool to identify molecular profile of tumors when biopsy is not feasible or there is limited tissue for analysis.

MICROSCOPIC AND MOLECULAR DIAGNOSIS OF Ascaridia spp. IN DOMESTIC PIGEONS(Columba livia domestica) IN BAGHDAD CITY,IRAQ

2020 ◽  
Vol 51 (4) ◽  
pp. 1220-1225
Author(s):  
Faraj & Al- Amery
Keyword(s):  
Molecular Diagnosis ◽  
Columba Livia ◽  
Ascaridia Galli ◽  
Molecular Assay ◽  
Infection Rates ◽  
Conventional Pcr ◽  
Significant Difference ◽  
Pcr Products ◽  
Males And Females ◽  
Domestic Pigeons

Ascaridiosis is a very important parasitic disease of birds, it is caused by Ascaridia. This study was conducted to identify the Ascaridia species by microscopic and molecular assay in Baghdad city. One hundred and sixty fecal samples were collected from domestic pigeons during the period from 1/1/ 2019 to 31/3/ 2019.  Results showed that the rate of infection for Ascaridia spp. 15.62% by microscopic examination.  Significant difference was observed in infection rates between males and females pigeons. Fifty samples randomly selected and subjected to molecular diagnosis of Ascaridia  spp.. Molecular examination results, the total infection rate showed 16%(8/50). The eight  positive PCR products were sequenced and deposited in Gene bank data base, phylogenic analysis demonstrated that 4 sequences belongs to Ascaridia galli ( MK918635.1, MK918636.1, MK918847.1, MK919081.1), while 2 (MK919199.1, MK919200.1) belong to  Ascaridia nymphii and 2 (MK919207.1, MK919264.1)  belong to Ascaridia numidae. It is the first study in Iraq to diagnosis of  Ascaridia nymphii and Ascaridia numidae  in domesticed pigeons by using conventional PCR.

scholarly journals Matched-Pair Analysis of Survival in the Patients with Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma Treated with Induction Chemotherapy Plus Chemo-Radiation or Total Laryngectomy

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1735
Author(s):  
Patricia García-Cabo ◽  
Fernando López ◽  
Mario Sánchez-Canteli ◽  
Laura Fernández-Vañes ◽  
César Álvarez-Marcos ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Organ Preservation ◽  
Matched Pair ◽  
Primary Tumors ◽  
Free Survival ◽  
Tumor Node Metastasis Stage ◽  
Significant Difference

Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex; Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75; 95% CI 0.48–1,18; P = 0.22) and disease-specific survival (DSS) (HR 0.98; 95% CI 0.52–1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931; 95% CI 0.57–1.71; P = 0.81), metastases-free survival (HR 2.23; 95% CI 0.67–7.41; P = 0.19), and the appearance of second primary tumors (HR 1.22; 95% CI 0.51–2.88; P = 0.64); Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival.

scholarly journals Assessment of new-onset depression and anxiety associated with COVID-19

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Eman Hurissi ◽  
Ethar Abu-jabir ◽  
Amnah Mohammed ◽  
Mashael Mahnashi ◽  
Sana Alharbi ◽  
...  
Keyword(s):  
Epidemiological Studies ◽  
Anxiety And Depression ◽  
Depression And Anxiety ◽  
Online Questionnaire ◽  
Final Sample ◽  
Significant Difference ◽  
Patient Health ◽  
Males And Females ◽  
Arabian Population ◽  
New Onset

Abstract Background Psychological disorders are common among individuals who experienced COVID-19. Previous studies have shown that females report higher depression and anxiety than males. The present study aims to test the differences in depression and anxiety between males and females who have experienced COVID-19. This a descriptive, observational, comparative study, among Saudi Arabian population. A total of 686 participants have been recruited. Participants completed an online questionnaire that contains questions about sociodemographic, COVID-19, Generalized Anxiety Disorder (GAD-7) questionnaire, and Patient Health Questionnaire (PHQ-9) to measure anxiety and depression, respectively. Results Twenty-six percent of the participants were excluded and our final sample consisted of 507 participants (median age 23; 65% females). Of the final sample, 23% (118) have been previously diagnosed with COVID-19. There is no significant difference in GAD-7 and PHQ-9 scores between COVID-19- positive and COVID-19-negative populations. However, females who have experienced COVID-19 reported significantly higher GAD-7 and PHQ-9 scores compared to males. Conclusion The results of our study show that females are significantly at a higher risk for depression and anxiety as a result of COVID-19 infection compared to males. Further epidemiological studies are required for a better understanding of this correlation.

scholarly journals Machine Learning and Radiomics Applications in Esophageal Cancers Using Non-Invasive Imaging Methods—A Critical Review of Literature

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2469
Author(s):  
Chen-Yi Xie ◽  
Chun-Lap Pang ◽  
Benjamin Chan ◽  
Emily Yuen-Yuen Wong ◽  
Qi Dou ◽  
...  
Keyword(s):  
Machine Learning ◽  
Quantitative Imaging ◽  
Risk Groups ◽  
Review Of Literature ◽  
Primary Tumors ◽  
Non Invasive ◽  
Significant Difference ◽  
Recent Developments ◽  
Health Significance ◽  
Imaging Markers

Esophageal cancer (EC) is of public health significance as one of the leading causes of cancer death worldwide. Accurate staging, treatment planning and prognostication in EC patients are of vital importance. Recent advances in machine learning (ML) techniques demonstrate their potential to provide novel quantitative imaging markers in medical imaging. Radiomics approaches that could quantify medical images into high-dimensional data have been shown to improve the imaging-based classification system in characterizing the heterogeneity of primary tumors and lymph nodes in EC patients. In this review, we aim to provide a comprehensive summary of the evidence of the most recent developments in ML application in imaging pertinent to EC patient care. According to the published results, ML models evaluating treatment response and lymph node metastasis achieve reliable predictions, ranging from acceptable to outstanding in their validation groups. Patients stratified by ML models in different risk groups have a significant or borderline significant difference in survival outcomes. Prospective large multi-center studies are suggested to improve the generalizability of ML techniques with standardized imaging protocols and harmonization between different centers.

scholarly journals Inter-Limb Jump Asymmetries and Their Association with Sport-Specific Performance in Young Male and Female Swimmers

2021 ◽  
Vol 18 (14) ◽  
pp. 7324
Author(s):  
Max I. Phukan ◽  
Rohit K. Thapa ◽  
Gopal Kumar ◽  
Chris Bishop ◽  
Helmi Chaabene ◽  
...  
Keyword(s):  
National Level ◽  
Young Male ◽  
Front Crawl ◽  
Male And Female ◽  
Standing Long Jump ◽  
Significant Difference ◽  
Specific Performance ◽  
Long Jump ◽  
Males And Females ◽  
Level Of Agreement

This study aimed to examine inter-limb jump asymmetries and their association with sport-specific performance in young swimmers. Thirty-eight (male, n = 19; female, n = 19) regional/national level young swimmers (age: 12.3 ± 1.2 years; height: 159.6 ± 8.2 cm; body mass: 52.5 ± 9.2 kg) participated in this study. Inter-limb asymmetries were assessed for single-leg countermovement jump (SLCMJ) and single-leg standing long jump (SLSLJ). Sport-specific performance was evaluated using front crawl (i.e., 50 m and 25 m) and front crawl kick (i.e., 50 m and 25 m). The kappa coefficient revealed a “slight” level of agreement (Κ = 0.156, 0.184, and 0.197 for female, male, and all, respectively) between the direction of asymmetry for SLCMJ and SLSLJ, indicating that asymmetries rarely favored the same limb during both tests. A paired sample t-test showed a significant difference (p = 0.025) between asymmetry scores obtained in SLCMJ and SLSLJ. No significant difference was found in asymmetry scores between males and females (p = 0.099 to 0.977). Additionally, no association between asymmetry scores and sport-specific performance was observed (p > 0.05). Our findings highlight the independent nature of inter-limb asymmetries derived from SLCMJ and SLSLJ among young male and female swimmers. Further, our results suggest no association between jumping asymmetries and sport-specific performance.

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