Journal of cancer biology & research最新文献

The examination of the prostate biopsy procedure is essential in the optimization of the diagnostic pathway of such a prevalent affliction as prostate cancer among men worldwide. With the core needle biopsy being the standard of care for the diagnosis of prostate cancer, the ability to obtain quality core samples is directly related to patient treatment and diagnostic reliability. Needle deflection and dynamic tissue deformation are two chief sources of unrepresentative samples outside of human error. To assess how these factors affect overall histological sample quality and what variables influence deflection and deformation, a review of related literature was conducted. A literature search using keywords [(core prostate) OR (prostate)] AND [(biopsy) OR (needle)] AND [(histological) OR (fragmentation) OR (deflection) OR (deformation)] AND [(factors) OR (rate) OR (quality)]. The resulting articles were analysed for relevance of factors influencing histological sample quality. The objective of this review was to analyse trends in the literature and comprise a comprehensive analysis regarding the factors that positively and negatively affect the final histological quality of the core specimens. The results highlighted the velocity of needle insertion into the soft tissue as a variable affecting dynamic deformation, and the geometry of the bevelled biopsy needle tip combined with the application of a biopsy template impacting the deviation of the needle from the linear target. Friction forces also significantly influence the final product as related to these factors. This literature study highlights the crucial parameters of the biopsy procedure and provides for a basis to discuss the improvements to the system and its external components to improve overall patient care. This suggests further investigation of these factors through their manipulation in controlled environments is necessary to improve the effectiveness of the biopsy procedure.

Introduction: Breast cancer has remained the most commonly diagnosed disease among women globally. Despite the advancement in biomedical sciences leading to improve survival outcomes, some patients endure longer wait periods prior to initiation of treatment.

Objective: To elucidate the impact of treatment delay on breast cancer patient's quality of life and survivorship. Second was to determine the optimal length of time (delay) between breast cancer diagnosis and start of first treatment in order to improve prognosis and general health and well-being of survivors.

Methods: Systematic search of the literature was conducted across five electronic databases: Pub Med, EMBASE, CINAHL, Scopus and Science Direct as well as the reference list of all articles retrieved.

Results: A total of 33 articles were included in the evidence based systematic review, which comprised of 255,366 observations. The results of the studies were categorized under five main themes as: study characteristics, cancer staging and classification, treatment delay time definition and interval, treatment regimen classification and delay impact on quality of life and survival. Analyzed wait times from diagnosis to the initiation of first therapy ranged from 7 days to a period of over 180 days. Combinations of standardized treatment including loco-regional radiotherapy, systemic chemotherapy surgery as well as hormonal therapy were examined. Even though some of the studies showed mixed results, overall, findings indicated that early detection, diagnosis and initiation of treatment within 90 days increase survival.

Conclusions: Evidence revealed that delaying the initiation of treatment for breast cancer more than 90 days after diagnosis has a detrimental effect on disease free and overall well-being of survivors.

P38-regulated and activated kinase (PRAK/MAPKAPK5) is a serine/threonine kinase which lies downstream of the p38 and ERK3/4 MAP kinase pathways. PRAK plays diverse roles in the processes of cell growth, nutrient starvation response, programmed cell death, senescence and motility. PRAK has been shown to both promote and inhibit cell motility in different contexts. The pro-motility functions of PRAK are attributed mainly to cytoskeletal rearrangement occurring downstream of its phosphorylated substrate HSP27; however, it was recently shown that PRAK is required for motility in endothelial cells upstream of Focal adhesion kinase (FAK). Along with Src, FAK functions as a mediator of motility signaling through the phosphorylation of substrates in focal adhesions. Here, we show that PRAK, initially identified as a FAK substrate in an in situ/ kinase overlay assay, is a Src substrate, the phosphorylation of which directs PRAK to focal adhesions. Focal adhesion localization of PRAK was not found to affect cell motility, however transient over expression of PRAK inhibited motility in HeLa cells. This effect requires PRAK kinase activity and proceeds through an impairment of FAK activation via phosphorylation on Y861. Our studies demonstrate for the first time that PRAK is regulated by tyrosine phosphorylation, localizes to focal adhesions, and interacts physically with and can phosphorylate FAK/Src. Further we provide a novel mechanism for the inhibition of motility downstream of PRAK.

The unlimited growth potential of tumors depends on telomere maintenance and typically depends on telomerase, an RNA-dependent DNA polymerase, which reverse transcribes the telomerase RNA template, synthesizing telomere repeats at the ends of chromosomes. Studies in various model organisms genetically deleted for telomerase indicate that several recombination-based mechanisms also contribute to telomere maintenance. Understanding the molecular basis of these mechanisms is critical since some human tumors form without telomerase, yet the sequence is maintained at the telomeres. Recombination-based mechanisms also likely contribute at some frequency to telomere maintenance in tumors expressing telomerase. Preventing telomere maintenance is predicted to impact tumor growth, yet inhibiting telomerase may select for the recombination-based mechanisms. Telomere recombination mechanisms likely involve altered or unregulated pathways of DNA repair. The use of some DNA damaging agents may encourage the use of these unregulated pathways of DNA repair to be utilized and may allow some tumors to generate resistance to these agents depending on which repair pathways are altered in the tumors. This review will discuss the various telomere recombination mechanisms and will provide rationale regarding the possibility that L1 retrotransposition may contribute to telomere maintenance in tumors lacking telomerase.

BRCA1-associated ATM activator-1 (BRAT1) was identified by our group as a DNA damage response (DDR) protein, which can bind with many DDR proteins and regulates their functions after DNA damage. However, previous study has also implicated BRAT1 as a regulator of cell growth and apoptosis. In this study, targeted gene deletion showed that BRAT1 is critical in stability and serum-induced expression of mTOR and downstream protein. Conditional deletion of BRAT1 of mouse embryonic fibroblasts suppressed serum-induced cell cycling progress. Our results suggest that BRAT1 is essential factor for PIKK signaling cascades.

ATM, ATR and DNA-PK are critical for DNA damage response (DDR) and sequential repair, leading to genomic stability. In this study, we found the expression of these proteins is markedly induced by PMA during THP1 differentiation without the change in the level of transcripts. Also, inhibitors of these protein activity suppressed PMA-induced morphological change of THP1 cells. Our results suggest the potential roles of these DDR proteins in cellular differentiation.