Novel Evolutionary Models and Periodic Charts in p- and q-Individual Chromosomes of Auxiliary Lymph Node and Buccal Cells

Mehdipour, Parvin; Javan, Firoozeh; Atri, Morteza

doi:10.1155/2013/570946

Cited by 2 publications

(4 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Heterogeneity of Telomere length, reflects the cellular evolution, at genomic and somatic level 19,[43][44][45] . Evolutionary hypothesis of TL, was initially unveiled in primary BC and brain tumors (BT) to provide an unique marker for cancer clinical management including prognosis, prediction and planning for an early detection by the circulating tumor cell (CTCs).…”

Section: Heterogeneity In Telomere Lengthmentioning

confidence: 99%

“…Analysis with all probes showed that cells with positive signals correspond to 11.21% (4506/40.197) for ALN and 28.43% (2415/8494) for unaffected genomic cells. Adapted from: 45 Two cell populations, including normal and abnormal cells, were analyzed in order to assess their heterogeneity. The SCN and SI of FISH were used to characterize the STs presence in each or all chromosomes and to distinguish the p and q arms.…”

Section: Sub-telomeric Signals Introductionmentioning

confidence: 99%

“…Analysis with all probes showed that cells with positive signals correspond to 11.21% (4506/40.197) for ALN and 28.43% (2415/8494) for unaffected genomic cells. Adapted from:45…”

mentioning

confidence: 99%

See 2 more Smart Citations

Translating Single Cell Secrets to Cancer Evolution Accelerates Personalized Therapy

Mehdipour

2023

MRAJ

View full text Add to dashboard Cite

Successful cancer evolution (CE) relies on the sequential molecular and functional events including 1) telomere; 2) sub-telomere; 3) epigenetic; 4-6) hit-episodes; 7) an innovative cell cycle machinery, as the multi-phase, and 8) chromosomal abnormalities. In this regard, eight available, fundamental/evolutionary and strategic key information (Evolutionary- ID) presented. Telomere length (TL), has the fundamental role in cancer development, with serious challenges in the clinical managements. Breast cancer and brain tumor are an unresolved problem in Science and Medicine. Besides, an early and translatable diagnostic- prognostic-predictive platform, by considering the targets-ID, is required. Diverse TL in two cases affected with astrocytoma with grade IV, revealed to be 12500 and 15000 bp in tumor, and 10000 and 9000 bp at genomic level. Interestingly, TL is declined in the lymph node, i.e., occurrence of evolution. Sub-telomeres (STs) through the cellular journey, are the neighboring destination at genomic and somatic level. The evolutionary pattern of STs has not been, routinely, decoded to the personalized clinical managements. The ST-sequences, are diversely predisposed to variety of environmental factors and play influential role in healthy individuals and the patients. An early detection is available by analysis of the ST- hybridized signals in the biopsy of auxiliary lymph nodes (ALN), and/or by circulating tumor cells (CTCs) into the blood stream. Diverse pattern of signal frequency and intensity in individual chromosomes at both somatic (ALN) and genomic (lymphocytes) levels were remarkable. The most common involved targets included chromosomes 5 and 9, 16 and 19; with diverse intensity at p and q chromosomal arms respectively. These findings have the predisposing, and an initial influence through the patients’ course of disease. ST- signals, by providing the STs-ID, offer periodical and predictive, indices in cancer screening and therapy. Furthermore, the complementary, cell cycle protein expression (PE) including Ki67, cyclin D1, and cyclin E, accelerates an early clinical management through the period of disease based on the CTCs. Epigenetics is the next molecular destination by focusing on the genomic/somatic index, as an evolutionary Epigenetics-ID with its impact on the cancer management. The target panel is Ataxia Telangiectasia mutated gene (ATM) as the molecular marker and an initiator of different cancers. ATM has remarkable roles, including: 1) in DNA double strand break (DSB), 2) to initiate different types of neoplastic disorders, including cancer, and 3), polymorphism, D1853N as a peridisposing marker by initiating the hit process. The influential characteristics include: family history of neoplastic disorders through the pedigree, the key role of ATM promoter methylation, cooperation of ATM/Rb protein expression, D1853N- marker, telomere length (TL) and the clinico-pathological characteristics in different types of brain tumors, and the environmental factors. Interestingly, TL has an independent influence on the progressive cancer evolution. An early detection by CTCs based on the D1853N/Sub-TL/Cell cycle checkpoints based on the PE assay and molecular test facilitate an early detection and therapy, based on the personalized approach. By highlighting the preventive insight in Medicine, a brief record on the “Methylation in Chorionic villus samples (CVS)” with aim of an early detective strategy is provided. All nine CVS samples were methylated for the MCPH1 gene. An early detection is possible either through CV sampling or by the circulating CV cells in the maternal blood. Evolutionary Hit includes: presence of D1853N polymorphism of ATM, as the hit-initiator through an evolutionary and progressive molecular based sequential alterations led to discovery of three-hit hypothesis in a patient affected with astrocytoma. More hits include five, and eight- hit hypotheses in primary breast cancer patients. Such platforms are considered as the individualized model in cancer. The pedigrees and details at the molecular follow-up studies and functional alteration at protein level are available in the provided sections. Novel strategy of Cell cycle phases in breast cancer is the major intersection for cancer therapy. The novel cell cycle hypothesis (CCH) highlights the mosaic based of dual and/or multi-phases, as minor clones at single cell level in the breast cancer (BC) -patients, escorted by the normal cell population. Such mosaicism provided an archetypal, unique diagnostic and therapeutic model, by applying different mosaic patterns (MPs) as well as “G1/S, S/G2 and G1/S/G2, and accompanied by normal phases, as a sole including G1, S, and G2 at the single cells level. Diagnosis is based on the mode of signal copy numbers (SCN) and the related PE. Interestingly MPs were also unmasked in patients with chronic myelogeneous leukemia and other solid tumors. Finally, the predisposing/predictive/prognostic/preventive square provides an innovate CDKs inhibitor-based therapy in BC and other cancers. Personalized base cancer therapy is the confusing procedure and requires the pedigree-based data, personalized, evolutionary based information including molecular and functional at both genomic and somatic, at single cell level. The target territories comprise cell cycle phases, proteins, Telomere length, telomerase, sub-telomere, and Epigenetics. The aim is directing the cell cycle fundamental forces back to normal, by performing: 1) Applying personalized, single cell-based approach, at molecular, functional level, pedigree analysis, and balancing the micro-/macro-environmental factors, including nutrition. 2) Satisfactory high single cell enumeration based on the FISH and protein expression assays; 3) Decoding the required dosage and combined therapeutic regimens accordingly, 4) Unmasking the cell cycle combined (mosaic) phases including different Cyclins; and 5) Bilateral cooperation between Pharmacology, Medicine, and Cancer Genetics/cell biology. Let’s combine the evolutionary based strategy by translating the personalized data at molecular/ Functional/ Informative, and pedigree-based level to the personalized therapy.

show abstract

Section: Heterogeneity In Telomere Lengthmentioning

confidence: 99%

Section: Sub-telomeric Signals Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Translating Single Cell Secrets to Cancer Evolution Accelerates Personalized Therapy

Mehdipour

2023

MRAJ

View full text Add to dashboard Cite

show abstract

“…We have recently reported a different profile of FISH signal, which reflects a distinct copy number of ST sequences of buccal and ALN cells and provides a personalized signature for the progress of breast neoplasm (Mehdipour et al, ). Given this personalized insight, the aim of the present study was to analyze the ST profiles for distribution of hybridization signals and intensity of individual p and q Chr arms in non‐affected (genomic) and ALN cells of a female patient previously affected by primary proliferative ductal carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Personalized evolutionary hypothesis of breast neoplasm based on differential hybridization signals of subtelomeric probes

Mehdipour

Javan

Savad

et al. 2015

Cell Biology International

View full text Add to dashboard Cite

Few available data on the genomic-somatic evolution in breast cancer create limitation to provide the appropriate clinical managements. As an example, human subtelomeres (ST) are diverse-prone and variable targets. STs, as hot spots, have positive and negative impacts on the status of health and malady. We showed higher subtelomere signal copy number (SCN) of specific chromosomes in genomics than in auxiliary lymph node (ALN). Dissimilarity of signal intensity (SI) is found for all chromosomes. Significantly higher SI in genomics than in ALN cells were specified as chromosomes 5, 6, 9-12, 16-19 for weak; 1, 5-9, 19, X for medium; and 2, 5, 9, 10, 16, 18 for strong SI. For lacking, and presence of one and two SCNs; p/q ratio reflected differences for all chromosomes; but, 2, 3, 5, 7, 8, 10, 16, 18, 20, and X chromosomes were involved for three SCN. Chromosomes 1, 4, 9, 12, 17-19 lacked three SCN in ALN and lymphocytes. Weak SI ratio was higher in p- than in q-arm in majority of chromosomes. Manner of evolution and diversity in p- and q-arms is expressive of a novel definition as two diverse domains with a personalized insight. These data have been accompanied by periodic charts as ST array profiles which provide specific and individualized pattern in breast neoplasm. Such profiling at genomics level could be considered as a prediction through the patients' life. Moreover, subtelomere territory by interacting with protein expression of Ki67, cyclin D1, and cyclin E; and molecular targets including telomere length at genomics and somatic level provides package of information to bridge cancer cell biology to the cancer clinic as "puzzling paradigm."

show abstract

Novel Evolutionary Models and Periodic Charts in p- and q-Individual Chromosomes of Auxiliary Lymph Node and Buccal Cells

Cited by 2 publications

References 16 publications

Translating Single Cell Secrets to Cancer Evolution Accelerates Personalized Therapy

Translating Single Cell Secrets to Cancer Evolution Accelerates Personalized Therapy

Personalized evolutionary hypothesis of breast neoplasm based on differential hybridization signals of subtelomeric probes

Contact Info

Product

Resources

About