Background/Aim: To date, several proteomics studies in cervical cancer (CC) have focused mainly on squamous cervical cancer (SCC). Our study aimed to discover and clarify differences in SCC and CAD that may provide valuable information for the identification of proteins involved in tumor progression, in CC as a whole, or specific for SCC or CAD. Materials and Methods: Total protein extracts from 15 individual samples corresponding to 5 different CC tissue types were compared with a non-cancerous control group using bidimensional liquid chromatography-mass spectrometry (2D LC-MS/MS), isobaric tags for relative and absolute quantitation (ITRAQ), principal component analysis (PCA) and gene set enrichment analysis (GSEA). Results: A total of 622 statistically significant different proteins were detected. Exocytosis-related proteins were the most over-represented, accounting for 25% of the identified and quantified proteins. Based on the experimental results, reticulocalbin 3 (RCN3) and Ras-related protein Rab-14 (RAB14) were chosen for further downstream in vitro and vivo analyses. RCN3 was overexpressed in all CC tissues compared to the control and RAB14 was overexpressed in squamous cervical cancer (SCC) compared to invasive cervical adenocarcinoma (CAD). In the tumor xenograft experiment, RAB14 protein expression was positively correlated with increased tumor size. In addition, RCN3-expressing HeLa cells induced a discrete size increment compared to control, at day 47 after inoculation. Conclusion: RAB14 and RCN3 are suggested as potential biomarkers and therapeutic targets in the treatment of CC.Cervical cancer (CC) is the fourth most frequently diagnosed cancer in women, with an estimated 265,000 deaths worldwide (1). A large majority (around 80%) of the global burden occurs in the less developed countries (2). Careful retrospective investigations have strongly implicated highrisk human papillomavirus (HPV) with cervical carcinogenesis (3). Although CC diagnosis and treatment programs have decreased the number of cases and mortality rates, the prognosis and complete response to treatment remain poor in CC variants (4,5). Approximately 80% of the CC cases worldwide are of the squamous cervical cancer (SCC) type, with the remainder being invasive cervical adenocarcinoma (CAD) (6). The incidence of CAD has increased, especially in younger women (7). During the last two decades, the relationship between CAD and SCC and all CCs has doubled even in developed countries. This epidemiological evidence suggests that current screening practices are inadequate to identify a significant proportion of CAD precursor lesions (8).In a population-based study in Korean women, it was shown that the prevalence of HPV in CAD tissue is approximately 90% (9). The infection of HPV 16 and/or HPV 18 accounted for 78% of HPV-positive CADs, and multiple HPV types were found in the remaining 13% of cases (9). Risk factors for developing CC that have been described in SCC include the use of oral contraceptives for more than five years, smokin...
The incidence of significant hypercalcemia in 305 women with disseminated breast cancer was 7.2%. 13 patients developed hypercalcemia spontaneously and eight patients developed hypercalcemia shortly after initiation of additive hormone therapy. One patient developed fatal hypercalcemia shortly after adrenalectomy. All patients had bone metastases documented by X-rays or bone scans. Treatment with volume expansion, diuretics, and steroids was successful in 11 of 19 trials and Mithramycin therapy in very low dosage was successful in 4 of 5 trials. 7 of the 22 hypercalcemia patients expired and four of these deaths were directly as a result of hypercalcemia.
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