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Journal of Cancer Research Updates

P53 Codon 72 and Endometrium Cancer
Pages 149-152
F. Gloria-Bottini, M. Nicotra, C. Spina, P.L. Benedetti-Panici, P. Saccucci, A. Neri, A. Magrini and E. Bottini

DOI: http://dx.doi.org/10.6000/1929-2279.2015.04.04.2

Published: 26 November 2015

 


Abstract: Background: The possible role p53 codon 72 in endometrium cancer has been investigated in several human populations: a positive association with the Pro variant has been observed in Asiatic but not in Caucasian populations. We reasoned that polymorphisms associated with endometrium cancer may interact with p53 codon 72 influencing the degree of association between this polymorphism and cancer.

Methods: Sixty nine women admitted to the hospital for endometrium cancer and 473 healthy subjects were studied in the White population of Rome. Verbal consent was obtained from these subjects to participate to the study that was approved by the Department. P53 codon 72, ADA1, ADA6 and PTPN22 genotypes were determined by DNA analysis Statistical analysis were performed by using commercial software (SPSS).

Results: The joint genotype carrying the *Pro allele of p53 codon 72and the ADA1*2 allele, the joint genotype carrying the *Pro allele and ADA6 *1 allele and the joint genotype carrying the *Pro allele and *C/*C genotype of PTPN22 show a proportion greater in cancer than in controls. The proportion of *Pro allele carriers in endometrium cancer shows a positive correlation (p=0.019) with the number of genetic factors considered i.e. ADA1,ADA6, PTPN22.

Conclusion: Our data suggest that the strength of association between the disease and p53 codon 72 depends on other genetic factors. Thus the different patterns of association between p53 codon 72 and endometrium cancer observed among human populations could be at least in part related to differences in allelic frequencies of these genetic factors.

Keywords: Endometrium cancer, p53 codon 72, ADA1, ADA6, PTPN22.

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Journal of Cancer Research Updates

Nanodiagnostic and Nanotherapeutic Molecular Platforms for Cancer Management
Pages 153-162
A. Lyberopoulou, E.P. Efstathopoulos and M. Gazouli

DOI: http://dx.doi.org/10.6000/1929-2279.2015.04.04.3

Published: 26 November 2015

 


Abstract: Over the last ten years rapid progress is being made regarding the incorporation of nanoparticles in cancer diagnosis and treatment. Besides the limitations that have to be addressed, there are various research studies suggesting some promising nanodiagnostic and nanotherapeutic platforms for cancer managment. Nanotherapeutic platforms are based on the localized application of nanoparticles using targeting moieties, most usually antibodies, in order to in vivo direct nanoparticles to cancer cells. Thereafter, either nanoparticles react to external stimulus, for example under radiofrequency waves nanoparticles generate thermal energy, or they are used for targeted drug-delivery platforms, which allows the augmentation of drug concentration in the cancerous site of the body and thus minimizing side effects and increasing the efficacy of the drug. Regarding nanodiagnostics, particular focus is paid on nanoparticles that can act as contrast agents in cancer imaging for in vivo nanodiagnostics and on nanobiochips and nanobiosensor, devices that incorporate the “lab on a chip” notion for in vitro nanodiagnostics. In this review, several advanced nanodiagnostic and nanotherapeutic platforms are discussed, on the development of more effective and targeted molecular techniques in the diagnosis and treatment of cancer.

Keywords: Nanotechnology, cancer, nanodiagnostics, nanotherapeutics.

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Journal of Cancer Research Updates

Positive Association between the Polymorphic Variant CCND1 A870G and Colorectal Cancer in Ecuadorian Mestizo Population
Pages 163-170
César Paz-y-Miño, Carolina Salazar, Tania Zurita, Andrés López-Cortés, Ramiro Hidalgo, Felipe Rosales, Alexandra Montalvo and Paola E. Leone

DOI: http://dx.doi.org/10.6000/1929-2279.2015.04.04.4

Published: 26 November 2015

 


Abstract: Background: Colorectal cancer (CRC) is the fourth most common cause of cancer death worldwide and has an annual incidence of 917,000 cases. In Ecuador the CRC is the fifteenth most common form of cancer and the fourth leading cause of cancer deaths.

Aim: Our goal was to establish frequencies related to the polymorphic variants: (CA)n in the EGFR gene and A870G in the CCND1 gene and their influence on the development of CRC in the Ecuadorian population.

Methods: This is a retrospective case-control study consisting of colorectal cancer patients (n = 96 cancer tissues) compared to a control group (n = 62 adjacent healthy tissues). For the sequencing of the fragments, PCR and Sanger method was used.

Results: The polymorphic variant A870G in CCND1 has a genotype frequency for the common homozygous G/G = 0.69, for the heterozygous A/G = 0.25 and for the less frequent homozygous A/A = 0.06 in the control group. We studied 7 alleles, repeats 14-19 have been reported in other studies, but the 13 repeats allele was first described here. The most common number of repetitions was 18 with a frequency of 0.326 in patients and 0.25 in controls (χ2 = 22.58, p <0.01). The odds ratio showed that the risk of developing colorectal cancer is 5 times greater if the individual is carrying the heterozygous G/A (p <0.01). Meanwhile, if the individual is carrying the allele 'A' the risk is 4 times more likely to develop this disease (p <0.01).

Keywords: Colorectal cancer, CCND1, A870G, polymorphic association.

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Journal of Cancer Research Updates

8-Cl-cAMP, “The Old Dog with New Tricks”: A Review
Pages 171-178
Vladan Bajić, Lada Živković, Andrea Čabarkapa and Biljana Spremo Potparević

DOI: http://dx.doi.org/10.6000/1929-2279.2015.04.04.5

Published: 26 November 2015

 


Abstract: Current chemotherapeutic drugs act for the most part by killing cancer cells directly. Treatment with these drugs often can be harmful to normal cells and may cause incomplete elimination of the target cells, resulting in the recurrence of the disease.

To coop with current treatments the path of biomodulation rather than cytotoxicity, has been seen in the role of cAMP in normal versus malignant cells. It has been found that an increase of cAMP levels in normal cells stimulates proliferation, and that in the same time cancerous cells are inhibited to proliferate. This inverted reaction has given the momentum for synthesis of various cAMP analogues and investigation of there antitumor activity. A number of analogues, such as 8-PIP-cAMP, 8-Br-CAMP or 8-HA–cAMP showed efficacy only in millimolar concentrations. Only one of them, 8-Cl-cAMP as specific analogue has achieved inhibition of proliferation and stimulation of apoptosis of malignant cells in low or micromole concentrations.

Still, 25 years later the mechanism of action of 8-clcAMP has not been fully elucidated or defined. This review is to challenge these mechanisms of action and to set a view of the nature of 8-Cl-cAMP action.

Keywords: 8-Cl-cAMP, PKA cAMP-dependent protein kinase, biomodulation.

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Journal of Cancer Research Updates

The Role of Exosomes and its Cargos in Drug Resistance of Cancer
Pages 179-187
Yujie Xie and Liwu Fu

DOI: http://dx.doi.org/10.6000/1929-2279.2015.04.04.6

Published: 26 November 2015

 


Abstract: Chemotherapy is one of the main therapies in cancer and plays an important role in controlling tumor progression, which can offer a longer overall survival (OS) for patients. But as the accumulation of drugs used in vivo, cancer cells develop drug resistance, even multi-drug resistance (MDR), that can cause failure of the whole therapy. The similar phenomenon can be observed in vitro. There are several mechanisms of drug resistance such as drug efflux, mediated by extracellular vesicles. Exosomes, a subset of extracellular vesicles (EVs), can be secreted by many types of cells and transfer proteins, lipids, and miRNA/mRNA/DNAs between cells in vitro and in vivo. Particularly cancer cells secrete more exosomes than healthy cells and resistance cells secrete more exosomes than sensitive cells. Exosomes have function of intercellular communication and molecular transfer, both associated with tumor growth, invasion, metastasis, angiogenesis, and drug resistance. In this paper, we will review the current knowledge regarding the emerging roles of exosomes and its cargo in drug resistance.

Keywords: Exosomes, drug resistance, drug efflux, antibody, miRNAs, lncRNA, P-glycoprotein, EMT.

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