Identification of a New Splice Variant of the Human ABCC6 Transporter

ABCC6 is a member of the adenosine triphosphate-binding cassette (ABC) gene subfamily C that encodes a protein (MRP6) involved in active transport of intracellular compounds to the extracellular environment. Mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), an autosomal recessive disorder of the connective tissue characterized by progressive calcification of elastic structures in the skin, the eyes, and the cardiovascular system. MRP6 is codified by 31 exons and contains 1503 amino acids. In addition to a full-length transcript of ABCC6, we have identified an alternatively spliced variant of ABCC6 from a cDNA of human liver that lacks exons 19 and 24. The novel isoform was named ABCC6 Δ19Δ24. PCR analysis from cDNA of cell cultures of primary human hepatocites and embryonic kidney confirms the presence of the ABCC6Δ19Δ24 isoform. Western blot analysis of the embryonic kidney cells shows a band corresponding to the molecular weight of the truncated protein

The Trend of CEACAM3 Blood Expression as Number Index of the CTCs in the Colorectal Cancer Perioperative Course

Pathological stage seems to be the major determinant of postoperative prognosis of solid tumors, but additional prognostic determinants need to be better investigated. The most important tumor marker for colorectal cancer (CRC) is the cell-surface antigen, Carcinoembryonic Antigen (CEA), and its assessment is considered a valuable index of circulating tumor cells (CTCs). In this paper, CEACAM3 evaluation was applied given its great specificity in the CRC. Whole blood from the basilic vein of 38 CRC patients was collected before and at various time intervals after the curative resection. Also, from 20 of them, we have obtained two additional intraoperative samples. CEACAM3 expression was evaluated in all the samples by RT-PCR. CEACAM3 duct values showed a decreasing trend from preoperative through early and later postoperative to 6th-month samples (p<0.001). The average values of CEACAM3 were related to the cancer size (T stage) (p=0.034) and WHO stage (p=0.035). A significant effect of the baseline value of CEACAM3 dCt on the temporal trend has been observed (p<0.001). In this study, we have demonstrated the CEACAM3 specificity and a perioperative trend of CTCs which is coherent with the clinical/pathological considerations and with previous experimental findings in different cancer types

Clinical and prognostic significance of central and obstructive apnoeas in patients with transthyretin cardiac amyloidosis

Aims: Central (CA) and obstructive apneas (OA) are highly prevalent in patients with chronic heart failure (HF) and transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized HF etiology. This study aimed to investigate the prevalence and impact of CA and OA in patients with ATTR-CA. Methods: Consecutive patients with ATTR-CA underwent a 24-hour ambulatory cardiorespiratory monitoring to evaluate the prevalence and severity of breathing disorders. The severity of these disorders was quantified using the apnea-hypopnea index (AHI). Accordingly, patients were categorized as having normal breathing (NB, AHI &lt;5 events/hour), obstructive apnea (OA, AHI ≥5 events/hour with &gt;50% being obstructive), or central apnea (CA, AHI &gt;5 events/hour with ≥50% being central). The primary endpoint at follow-up was all-cause mortality. Results: Out of 142 patients enrolled (n=142, aged 77±7 years, 91% males, 96% wild-type ATTR-CA), considering the 24 hours, 20% had NB (39% at daytime, 8% at nighttime), while 35% had CA (45% at daytime, 39% at nighttime) and 45% had OA (25% at daytime, 54% at nighttime). After a median 2.3 (1.4-3.3) years follow-up, 24-hour, daytime, and nighttime AHI were higher in non-survivors vs. survivors (all p&lt;0.05), independently of the prevalent apnea type (p=0.64). At multivariable regression analysis (adjusted for the possible clinical, echocardiographic, and biohumoral confounders), nighttime AHI ≥30 events/hour (hazard ratio 2.37 [95%CI 1.07-5.23], p=0.033) and hs-troponin T (hazard ratio 2.43 [95%CI 1.42-4.17], p=0.001) were predictors of mortality. Conclusion: CA and OA are highly prevalent both at daytime and nighttime in patients with ATTR-CA and are associated with higher mortality