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1.
Nature ; 616(7957): 534-542, 2023 04.
Article in English | MEDLINE | ID: mdl-37046095

ABSTRACT

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Clonal Evolution , Clone Cells , Evolution, Molecular , Lung Neoplasms , Neoplasm Metastasis , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Clone Cells/pathology , Cohort Studies , Disease Progression , Lung Neoplasms/pathology , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/pathology , Neoplasm Recurrence, Local
2.
Open Access Maced J Med Sci ; 7(21): 3608-3614, 2019 Nov 15.
Article in English | MEDLINE | ID: mdl-32010385

ABSTRACT

BACKGROUND: The fractures of hip joint considered as a serious problem in public health in the medical and socioeconomic issues, the incidence of the fracture neck femur is significantly increased with the increment of general population life span. AIM: The goal of this study is to highlight and focus on the most important risk factor for the hip fractures in our Babylon society, and to improve our understanding of the medical and social aspects of these predisposing factors. PATIENTS AND METHODS: A case-control study of older adults (above 60 years old). The study was done on tow samples. First, one consisting of 75 cases those having fracture neck femur considered as cases, and second sample as a control group, consisting of 150 people as a healthy control group having no fracture. A pre-tested questionnaire was prepared to collect data from both samples; the questionnaire included demographic data and information about potential risk factors of hip fracture. RESULTS: Most of the people in the study samples in both groups were, married women, housekeepers, illiterate and from urban dwellers. There was highly significant association between case-control groups regarding, Continuous using of medication such as cortisone which was found to be a potential risk factor of hip fracture (Unadjusted OR = 3.636), low income was positively associated risk factor of hip fracture in this study (OR = 2.377), low milk intake, low sun exposure, tobacco smoking were positively associated with this health problem (OR = 1.794), while physical exercise was protective factor (OR = 0.489). CONCLUSION: The highest risk factors associated with increased occurrence of hip fracture were using cortisone, Osteoporosis, tobacco smoking, consuming soft drinks, and less exposure to sunlight.

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