Voltage-gated calcium channels play a major role in many important processes including muscle contraction, neurotransmission, excitation-transcription coupling, and hormone secretion. To date, 10 calcium channel ␣ 1 -subunits have been reported, of which four code for L-type calcium channels. In our previous work, we uncovered by transcript-scanning the presence of 19 alternatively spliced exons in the L-type Ca v 1.2 ␣ 1 -subunit. Here, we report the smooth muscle-selective expression of alternatively spliced exon 9* in Ca v 1.2 channels found on arterial smooth muscle. Specific polyclonal antibody against exon 9* localized the intense expression of 9*-containing Ca v 1.2 channels on the smooth muscle wall of arteries, but the expression on cardiac muscle was low. Whole-cell patch clamp recordings of the 9*-containing Ca v 1.2 channels in HEK293 cells demonstrated ؊9 and ؊11-mV hyperpolarized shift in voltage-dependent activation and current-voltage relationships, respectively. The steady-state inactivation property and sensitivity to blockade by nifedipine of the ؎exon 9* splice variants were, however, not significantly different. Such cell-selective expression of an alternatively spliced exon strongly indicates the customization and fine tuning of calcium channel functions through alternative splicing of the pore-forming ␣ 1 -subunit. The generation of proteomic variations by alternative splicing of the calcium channel Ca v 1.2 ␣ 1 -subunit can potentially provide a flexible mechanism for muscle or neuronal cells to respond to various physiological signals or to diseases.

Background Computed tomography (CT)-guided pulmonary core biopsies of small pulmonary nodules less than 15 millimeters (mm) are challenging for radiologists, and their diagnostic accuracy has been shown to be variable in previous studies. Common complications after the procedure include pneumothorax and pulmonary hemorrhage. The present study compared the diagnostic accuracy of small and large lesions using CT-guided core biopsies and identified the risk factors associated with post-procedure complications. Methods Between January 1, 2016, and December 31, 2017, 198 CT-guided core biopsies performed on 195 patients at our institution were retrospectively enrolled. The lesions were separated into group A (< or = 15 mm) and group B (> 15 mm) according to the longest diameter of the target lesions on CT. Seventeen-gauge introducer needles and 18-gauge automated biopsy instruments were coaxially used for the biopsy procedures. The accuracy and complications, including pneumothorax and pulmonary hemorrhage, of the procedures of each group were recorded. The risk factors for pneumothorax and pulmonary hemorrhage were determined using univariate analysis of variables. Results The diagnostic accuracies of group A (n = 43) and group B (n = 155) were 83.7 % and 96.8 %, respectively ( p = 0.005). The risk factors associated with post-biopsy pneumothorax were longer needle path length from the pleura to the lesion ( p = 0.020), lesion location in lower lobes ( p = 0.002), and patients with obstructive lung function tests ( p = 0.034). The risk factors associated with post-biopsy pulmonary hemorrhage were longer needle path length from the pleura to the lesion ( p < 0.001), smaller lesions ( p < 0.001), non-pleural contact lesions ( p < 0.001), patients without restrictive lung function tests ( p = 0.034), and patients in supine positions ( p < 0.003). Conclusion CT-guided biopsies of small nodules equal to or less than 15 mm using 17-gauge guiding needles and 18-gauge biopsy guns were accurate and safe. The biopsy results of small lesions were less accurate than those of large lesions, but the results were a reliable reference for clinical decision-making. Understanding the risk factors associated with the complications of CT-guided biopsies is necessary for pre-procedural planning and communication.

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The cancer-initiating capacity of most malignant tumours is considered to reside in a small subpopulation of cells. Therapeutical interventions should target these cells rather than the tumour mass. Numerous studies have shown that the carbohydrate antigen structure CD176 (Thomsen-Friedenreich antigen, core-1) is present in many types of cancer and absent in normal adult human tissues. In this study, we assessed whether CD176 is co-expressed with CD44 or CD133 [markers of cancer-initiating cells (CIC)] in human lung, breast and liver carcinoma. A variety of human cancer cell lines and surgical specimens of these malignancies were examined. It was found that in most cases the majority of tumour cells stained strongly for CD44 by immunohistochemistry and flow cytometry, whereas CD133 expression was found on a smaller, but varying proportion of cells. Co-expression of CD176 with CD44 was found at a surprisingly high percentage of cancer cells in vitro and in vivo. Co-expression of CD176 with CD133 was also detected, although at a lower rate. Tamoxifen treatment of MDA-435 breast cancer cells enhanced the CD44(+) /CD176(+) phenotype. Evidence is provided through a new sandwich solid-phase enzyme-linked immunosorbent assay (ELISA) suggesting that CD44 is a carrier molecule for CD176 not only in colorectal cancer as previously reported, but also in lung, breast and liver cancer. The expression of CD176 in CIC suggests that it may represent an effective target for tumour therapies.