BackgroundCervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population’s quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC.MethodsUsing clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle’s ability to discriminate CC from control samples.ResultsThe beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle’s success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients.ConclusionPresent data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.
Cervical cancer (CC) is associated with alterations in immune system balance, which is primarily due to a shift from Th1 to Th2 and the unbalance of Th17/Treg cells. Using in silico DNA copy number analysis, we have demonstrated that ~20% of CC samples exhibit gain of 8q22.3 and 19q13.31; the regions of the genome that encodes the KLF10 and PSG genes, respectively. Gene expression studies demonstrated that there were no alterations in KLF10 mRNA expression, whilst the PSG2 and −5 genes were up-regulated by 1.76 and 3.97-fold respectively in CC compared to normal tissue controls. siRNA and ChIP experiments in SiHa cells have demonstrated that KLF10 participates in immune response through regulation of IL6, IL25 and PSG2 and PSG5 genes. Using cervical tissues from KLF10−/− mice, we have identified down-regulation of PSG17, −21 and −23 and IL11. These results suggest that KLF10 may regulate immune system response genes in cervical cancer among other functions. KLF10 and PSG copy number variations and alterations in mRNA expression levels could represent novel molecular markers in CC.
Thymopoietin (TMPO) is an inner nuclear membrane protein, the coding gene named equally, can give arise to six isoforms by alternative splicing. This gene has been found up regulated in several types of cancer. At present work, we evaluated the TMPO isoforms generated by alternative splicing as well as the protein signal detection in breast cancer samples. TMPO expression was analyzed by immunohistochemistry in tissue microarray containing 46 breast tissue samples including normal (n = 6), benign lesions (n = 18) (fibroadenomas (n = 6), fibrocystic changes (n = 6), ductal hyperplasias (n = 6)) and breast carcinoma (n = 22). Isoforms -α, -β and -γ of TMPO were evaluated using RT-PCR; clinical-pathological correlation analysis were done by mean of X(2). Neither the normal nor the benign lesions of the breast showed positive TMPO immunodetection, whilst 45 % of the breast carcinomas were immunopositive (p = 0.000), nine of ten positives carcinomas correspond to the Luminal A subtype. Further, alpha isoform was present in all breast samples analyzed; however, beta and gamma isoforms were only present in ten (p = 0.003) and 17 (p = 0.000), respectively, in the breast cancer samples. According with the present data, we suggest that TMPOβ and -γ isoforms could provide a potential reliable diagnostic marker for breast cancer.
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