Acromegaly is associated with increased cancer risk: a survey in Italy
In conclusion, we found evidence that acromegaly in Italy is associated with a moderate increase in cancer risk. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Terzolo, M., Reimondo, G., Berchialla, P., Ferrante, E., Malchiodi, E., De Marinis, L., Pivonello, R., Grottoli, S., Losa, M., Cannavo, S., Ferone, D., Montini, M., Bondanelli, M., De Menis, E., Martini, C., Puxeddu, E., Velardo, A., Peri, A., Faustini-Fu Tags: Research Source Type: research
Allosteric alterations in the androgen receptor and activity in prostate cancer
Organisms have evolved to generate biological complexity in their proteome and transcriptome from a limited number of genes. This concept holds true for the androgen receptor, which displays a diversity of inclusion/exclusion events in its structural motifs as a mechanism of resistance to the most forefront anti-androgen therapies. More than 20 androgen receptor variants that lack various portions of ligand-binding domain have been identified in human prostate cancer (PCa) samples. Most of the variants are inactive on their own, with a few exceptions displaying constitutive activity. The full-length receptor and one or mor...
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Uo, T., Plymate, S. R., Sprenger, C. C. Tags: Review Source Type: research
Fighting tubulin-targeting anticancer drug toxicity and resistance
Tubulin-targeting drugs, like taxanes and vinca alkaloids, are among the most effective anticancer therapeutics used in the clinic today. Specifically, anti-microtubule cancer drugs (AMCDs) have proven to be effective in the treatment of castration-resistant prostate cancer and triple-negative breast cancer. AMCDs, however, have limiting toxicities that include neutropenia and neurotoxicity, and, in addition, tumor cells can become resistant to the drugs after long-term use. Co-targeting mitotic progression/slippage with inhibition of the protein kinases WEE1 and MYT1 that regulate CDK1 kinase activity may improve AMCD eff...
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Visconti, R., Grieco, D. Tags: Thematic Review Source Type: research
Consequences of mitotic slippage for antimicrotubule drug therapy
Antimicrotubule agents are commonly utilised as front-line therapies against several malignancies, either by themselves or as combination therapies. Cell-based studies have pinpointed the anti-proliferative basis of action to be a consequence of perturbation of microtubule dynamics leading to sustained activation of the spindle assembly checkpoint, prolonged mitotic arrest and mitotic cell death. However, depending on the biological context and cell type, cells may take an alternative route besides mitotic cell death via a process known as mitotic slippage. Here, mitotically arrested cells ‘slip’ to the next in...
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Cheng, B., Crasta, K. Tags: Thematic Review Source Type: research
Cell death response to anti-mitotic drug treatment in cell culture, mouse tumor model and the clinic
Anti-mitotic cancer drugs include classic microtubule-targeting drugs, such as taxanes and vinca alkaloids, and the newer spindle-targeting drugs, such as inhibitors of the motor protein; Kinesin-5 (aka KSP, Eg5, KIF11); and Aurora-A, Aurora-B and Polo-like kinases. Microtubule-targeting drugs are among the first line of chemotherapies for a wide spectrum of cancers, but patient responses vary greatly. We still lack understanding of how these drugs achieve a favorable therapeutic index, and why individual patient responses vary. Spindle-targeting drugs have so far shown disappointing results in the clinic, but it is possib...
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Shi, J., Mitchison, T. J. Tags: Thematic Review Source Type: research
Targeting mitotic pathways for endocrine-related cancer therapeutics
A colossal amount of basic research over the past few decades has provided unprecedented insights into the highly complex process of cell division. There is an ever-expanding catalog of proteins that orchestrate, participate and coordinate in the exquisite processes of spindle formation, chromosome dynamics and the formation and regulation of kinetochore microtubule attachments. Use of classical microtubule poisons has still been widely and often successfully used to combat a variety of cancers, but their non-selective interference in other crucial physiologic processes necessitate the identification of novel druggable com...
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Agarwal, S., Varma, D. Tags: Thematic Review Source Type: research
Centrosome amplification: a suspect in breast cancer and racial disparities
The multifaceted involvement of centrosome amplification (CA) in tumorigenesis is coming into focus following years of meticulous experimentation, which have elucidated the powerful abilities of CA to promote cellular invasion, disrupt stem cell division, drive chromosomal instability (CIN) and perturb tissue architecture, activities that can accelerate tumor progression. Integration of the extant in vitro, in vivo and clinical data suggests that in some tissues CA may be a tumor-initiating event, in others a consequential ‘hit’ in multistep tumorigenesis, and in some others, non-tumorigenic. However, in vivo d...
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Ogden, A., Rida, P. C. G., Aneja, R. Tags: Thematic Review Source Type: research
Germline mutation contribution to chromosomal instability
Genomic instability is a feature of cancer that fuels oncogenesis through increased frequency of genetic disruption, leading to loss of genomic integrity and promoting clonal evolution as well as tumor transformation. A form of genomic instability prevalent across cancer types is chromosomal instability, which involves karyotypic changes including chromosome copy number alterations as well as gross structural abnormalities such as transversions and translocations. Defects in cellular mechanisms that are in place to govern fidelity of chromosomal segregation, DNA repair and ultimately genomic integrity are known to contribu...
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Chan, S. H., Ngeow, J. Tags: Thematic Review Source Type: research
Role of chromosomal instability in cancer progression
Cancer cells often display chromosomal instability (CIN), a defect that involves loss or rearrangement of the cell’s genetic material – chromosomes – during cell division. This process results in the generation of aneuploidy, a deviation from the haploid number of chromosomes, and structural alterations of chromosomes in over 90% of solid tumours and many haematological cancers. This trait is unique to cancer cells as normal cells in the body generally strictly maintain the correct number and structure of chromosomes. This key difference between cancer and normal cells has led to two important hypotheses:...
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: McClelland, S. E. Tags: Thematic Review Source Type: research
50 years on ... the discovery of tubulin continues to advance cancer treatment
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Crasta, K., Aneja, R. Tags: Editorials Source Type: research
Lessons from bacterial homolog of tubulin, FtsZ for microtubule dynamics
FtsZ, a homolog of tubulin, is found in almost all bacteria and archaea where it has a primary role in cytokinesis. Evidence for structural homology between FtsZ and tubulin came from their crystal structures and identification of the GTP box. Tubulin and FtsZ constitute a distinct family of GTPases and show striking similarities in many of their polymerization properties. The differences between them, more so, the complexities of microtubule dynamic behavior in comparison to that of FtsZ, indicate that the evolution to tubulin is attributable to the incorporation of the complex functionalities in higher organisms. FtsZ an...
Source: Endocrine-Related Cancer - August 14, 2017 Category: Endocrinology Authors: Battaje, R. R., Panda, D. Tags: Thematic Review Source Type: research
Hashimotos thyroiditis predicts outcome in intrathyroidal papillary thyroid cancer
In conclusion, our data show that HT represents an independent prognostic parameter in intrathyroidal PTC, but cannot improve prognostic specificity. (Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - August 7, 2017 Category: Endocrinology Authors: Marotta, V., Sciammarella, C., Chiofalo, M. G., Gambardella, C., Bellevicine, C., Grasso, M., Conzo, G., Docimo, G., Botti, G., Losito, S., Troncone, G., De Palma, M., Giacomelli, L., Pezzullo, L., Colao, A., Faggiano, A. Tags: Research Source Type: research
Progression-free survival as a surrogate endpoint in advanced neuroendocrine neoplasms
In oncology clinical trials, overall survival (OS) is considered the gold standard outcome measure. In phase III trials for neuroendocrine neoplasms (NENs), however, progression-free survival (PFS) is more frequently used, as NENs are relatively rare and indolent neoplasms. But this surrogacy of PFS for OS has never been systematically validated. We, therefore, performed a literature-based analysis of phase II and III trials for NENs to evaluate the correlation between PFS and OS in NENs treated with medical treatment. We identified phase II and III clinical trials of medical treatment for advanced NENs based on a systemat...
Source: Endocrine-Related Cancer - August 7, 2017 Category: Endocrinology Authors: Imaoka, H., Sasaki, M., Takahashi, H., Hashimoto, Y., Ohno, I., Mitsunaga, S., Watanabe, K., Umemoto, K., Kimura, G., Suzuki, Y., Ikeda, M. Tags: Research Source Type: research
Genetic and epigenetic drivers of neuroendocrine tumours (NET)
Neuroendocrine tumours (NET) of the gastrointestinal tract and the lung are a rare and heterogeneous group of tumours. The molecular characterization and the clinical classification of these tumours have been evolving slowly and show differences according to organs of origin. Novel technologies such as next-generation sequencing revealed new molecular aspects of NET over the last years. Notably, whole-exome/genome sequencing (WES/WGS) approaches underlined the very low mutation rate of well-differentiated NET of all organs compared to other malignancies, while the engagement of epigenetic changes in driving NET evolution i...
Source: Endocrine-Related Cancer - August 7, 2017 Category: Endocrinology Authors: Di Domenico, A., Wiedmer, T., Marinoni, I., Perren, A. Tags: Review Source Type: research
Expression and mutational status of USP8 in tumors causing ectopic ACTH secretion syndrome
(Source: Endocrine-Related Cancer)
Source: Endocrine-Related Cancer - August 7, 2017 Category: Endocrinology Authors: Perez-Rivas, L. G., Osswald, A., Knosel, T., Lucia, K., Schaaf, C., Hristov, M., Fazel, J., Kirchner, T., Beuschlein, F., Reincke, M., Theodoropoulou, M. Tags: Research Letter Source Type: research
