▪ Has Cancer Sculpted the Genome? Modeling Linkage and the Role of Tetraploidy in Neoplastic Progression

2010 ◽  
pp. 70-91
Keyword(s):  
Neoplastic Progression

Neoplastic conversion of preneoplastic Syrian hamster cells: rate estimation by fluctuation analysis

1983 ◽  
Vol 3 (5) ◽  
pp. 931-945
Author(s):  
B D Crawford ◽  
J C Barrett ◽  
P O Ts'o
Keyword(s):  
Syrian Hamster ◽  
Neoplastic Transformation ◽  
Solid Substrate ◽  
Established Cell Line ◽  
Fluctuation Analysis ◽  
Neoplastic Progression ◽  
Early Passage

Analysis of the role of gene mutations in the multistep process of neoplastic transformation requires that the discrete steps in carcinogenesis first be dissected. Toward this end, we have isolated and characterized preneoplastic Syrian hamster cells which exhibit in vitro a trait highly correlated with neoplastic conversion in vivo. Previous findings (J. C. Barrett, Cancer Res. 40:91-94, 1980) indicate that spontaneous neoplastic transformation of Syrian hamster cells occurs in at least two steps. An intermediate stage, characterized by an aneuploid established cell line which has a propensity to become neoplastic spontaneously upon further growth in vitro, has been described. These preneoplastic cells differ from diploid early-passage Syrian hamster cells in becoming capable of anchorage-independent growth in semisolid agar, as well as becoming neoplastic in vivo when attached to a solid substrate. Evidence presented here demonstrates that anchorage-independent conversion in vitro is a reliable marker for neoplastic conversion in this cell system. Fluctuation analyses, patterned after those described by Luria and Delbruck for microbial genetics, demonstrate that anchorage-independent variants are generated randomly from clonally derived preneoplastic cells at the rate of 10(-8) to 10(-7) variants per cell per generation. These results establish a multistep stochastic process for transformation in vitro and indicate that conversion to anchorage independence may be necessary for Syrian hamster cells to become tumorigenic. The possible role of gene mutation in this step during neoplastic progression is discussed.

scholarly journals PD-L1 Expression in TNBC: A Predictive Biomarker of Response to Neoadjuvant Chemotherapy?

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Bruna Cerbelli ◽  
Angelina Pernazza ◽  
Andrea Botticelli ◽  
Lucio Fortunato ◽  
Massimo Monti ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Predictive Biomarker ◽  
Complete Response ◽  
Response To Therapy ◽  
Neoplastic Progression ◽  
Infiltrating Lymphocytes

Triple negative breast cancer (TNBC) has an aggressive clinical behaviour, with a poorer prognosis compared to other subtypes. Recently, tumor-infiltrating lymphocytes (TILs) have been proposed as a predictive biomarker for a better clinical outcome and pathological response (pR) after neoadjuvant chemotherapy (NACT) in TNBC. These data confirm the role of the immune system in the neoplastic progression and in the response to therapy. We performed a retrospective analysis of 54 pre-NACT biopsies of TNBC and compared both the percentage of stromal TILs and the degree of PD-L1 expression with the extent of pR to standard NACT. A pathological complete response (pCR) was achieved in 35% of cases. Univariate analysis showed (i) a significant association between PD-L1 expression in ≥25% of neoplastic cells and the achievement of a pCR (p=0.024); (ii) a significantly higher frequency of pCR in cases showing ≥50% stromal TILs (p<0.001). However in the multivariate analysis only PD-L1 expression on tumor cells remained significantly associated with pCR (OR = 1,13; 95% CI 1,01–1,27), suggesting that the expression of this biomarker could be associated with a subpopulation of TNBC more likely to respond to chemotherapy. These data need to be confirmed by larger studies.

scholarly journals Neoplastic conversion of preneoplastic Syrian hamster cells: rate estimation by fluctuation analysis.

1983 ◽  
Vol 3 (5) ◽  
pp. 931-945 ◽  
Author(s):  
B D Crawford ◽  
J C Barrett ◽  
P O Ts'o
Keyword(s):  
Syrian Hamster ◽  
Neoplastic Transformation ◽  
Solid Substrate ◽  
Established Cell Line ◽  
Fluctuation Analysis ◽  
Neoplastic Progression ◽  
Early Passage

Analysis of the role of gene mutations in the multistep process of neoplastic transformation requires that the discrete steps in carcinogenesis first be dissected. Toward this end, we have isolated and characterized preneoplastic Syrian hamster cells which exhibit in vitro a trait highly correlated with neoplastic conversion in vivo. Previous findings (J. C. Barrett, Cancer Res. 40:91-94, 1980) indicate that spontaneous neoplastic transformation of Syrian hamster cells occurs in at least two steps. An intermediate stage, characterized by an aneuploid established cell line which has a propensity to become neoplastic spontaneously upon further growth in vitro, has been described. These preneoplastic cells differ from diploid early-passage Syrian hamster cells in becoming capable of anchorage-independent growth in semisolid agar, as well as becoming neoplastic in vivo when attached to a solid substrate. Evidence presented here demonstrates that anchorage-independent conversion in vitro is a reliable marker for neoplastic conversion in this cell system. Fluctuation analyses, patterned after those described by Luria and Delbruck for microbial genetics, demonstrate that anchorage-independent variants are generated randomly from clonally derived preneoplastic cells at the rate of 10(-8) to 10(-7) variants per cell per generation. These results establish a multistep stochastic process for transformation in vitro and indicate that conversion to anchorage independence may be necessary for Syrian hamster cells to become tumorigenic. The possible role of gene mutation in this step during neoplastic progression is discussed.

scholarly journals Multiple HPV infection as possible marker of neoplastic progression

2020 ◽  
Author(s):  
Maria Teresa Bruno ◽  
Guido Scalia ◽  
Nazario Cassaro ◽  
Sara Boemi
Keyword(s):  
Prognostic Factor ◽  
Uterine Cervix ◽  
Hpv Infection ◽  
Multiple Infections ◽  
Neoplastic Progression ◽  
Hpv 16 ◽  
Cervical Biopsy ◽  
Neoplastic Lesions ◽  
Polymerase Chain

Abstract Background : Some studies in the literature suggest a possible role of multiple HPV infections as a prognostic factor in the development and progression of cervical neoplasia. we studied the cases of single and multiple HPV infection and analyzed the correlation with negative cases, and preneoplastic and neoplastic lesions of the uterine cervix with the aim of making a contribution to the prognostic factor under discussion Methods: 921 women with clinical HPV manifestations were enrolled. Inclusion criteria were: positive at the cytology for HPV lesions, presence of preneoplastic and neoplastic lesions of the uterine cervix diagnosed by the histology examination All the patients underwent colposcopy and cervical biopsy with viral genotyping. The search for viral DNA was carried out using polymerase chain reaction. Genotype 16 is correlated with the majority of CIN2+; we divided the multiple HPV16 infections into “infections with 16 as the first genotype” (16mHPV) (e.g. HPV 16 , 31, 52) and into “ infections containing 16” (m16HPV) (e.g. HPV 31, 16 , 52), we then divided them based on the number of genotypes present: infections with 2 strains, 3 strains, 4 strains, and > 4 strains. Results: We analyzed the differences between single and multiple infections with HPV16, the patients with single infections had a higher incidence of CIN2+ (83.3%) with respect to those with multiple infections (71.4%). The 16mHPV infection was significative for CIN2/CIN3. When the prevalence of the combinations between the genotypes was studied, we found that in 16mHPV infection HPV16, 18 and HPV 16, 31 were the most common combinations of mHPV infection (50%) and the most frequent in CIN2/CIN3 The 16mHPV infection with 2 genotypes, with respect to the infections with 3 or more genotypes, was significative with an OR= 7.94 (IC% 2.55-24.73). Conclusions: Our results suggest that single HPV infections give a higher risk of SCC development with respect to multiple HPV infections. Among multiple infections, only 16mHPV infection with 2 genotypes is associated with CIN2/CIN3 in a significative way and it presents an 8 times greater risk of developing a high grade lesion.

scholarly journals Hypoxic Regulation of Neutrophils in Cancer

2019 ◽  
Vol 20 (17) ◽  
pp. 4189 ◽  
Author(s):  
Daniel Triner ◽  
Yatrik M. Shah
Keyword(s):  
Transcription Factors ◽  
Therapeutic Target ◽  
Human Cancer ◽  
Critical Role ◽  
Neutrophil Function ◽  
Neoplastic Progression ◽  
Specific Expression ◽  
Microbial Response ◽  
Novel Therapeutic

Neutrophils have been well-characterized for their role in the host anti-microbial response. However, it is now appreciated that neutrophils have a critical role in tumorigenesis and tumor progression in the majority of solid tumors. Recent studies have indicated a critical role for hypoxia in regulating neutrophil function in tumors. Furthermore, neutrophil-specific expression of hypoxia-inducible transcription factors may represent a novel therapeutic target for human cancer. In this review, we highlight the function of neutrophils in cancer and the role of the neutrophil hypoxic response in regulating the neoplastic progression of cancer.

scholarly journals P12.05 Role of Dkk-3 in the neoplastic progression of meningiomas. Could it represent a new therapeutic target?

2017 ◽  
Vol 19 (suppl_3) ◽  
pp. iii95-iii96
Author(s):  
M. Caffo ◽  
L. Minutoli ◽  
V. Barresi ◽  
E. Esposito ◽  
M. Campolo ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Neoplastic Progression
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