Transforming growth factor-a (TGF-a)-induced proliferation and transforming growth factor-b (TGF-b)-mediated quiescence are intricately balanced in normal lung-tissue homeostasis but are deregulated during neoplastic progression of lung cancer. Here, we show that Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2), a novel MYCinteracting transcriptional modulator, responds to TGF-a induction and TGF-b suppression to orchestrate cellular proliferation and quiescence, respectively. Upon TGF-a induction, CITED2 was induced by MYC and further modulated MYC-mediated transcription in a feed-forward manner. CITED2 recruited p300 to promote MYC-p300-mediated transactivation of E2F3, leading to increased G1/S cell cycle progression. Moreover, CITED2 inhibited cellular quiescence by enhancing MYC-mediated suppression of p21 CIP1 . CITED2 interacted with histone deacetylase 1 (HDAC1) and potentiated MYC-HDAC1 complex formation. TGF-b stimulation provoked downregulation of CITED2, which abrogated MYC-HDAC1-mediated p21 CIP1 suppression, causing cellular quiescence. Ectopic CITED2 expression enhanced tumor growth in nude mice; furthermore, CITED2 knockdown caused tumor shrinkage and increased overall host mouse survival rates. Expression of CITED2/MYC/E2F3/ p21 CIP1 signaling molecules was associated with poor prognosis of lung cancer patients. Thus, CITED2 functions as a molecular switch of TGF-a and TGF-b-induced growth control, and MYC-CITED2 signaling axis provides a new index for predicting clinical outcome.

The aim of this study is to determine whether pet dogs owned by patients with systemic lupus erythematosus (SLE) are at a higher risk of developing SLE. Diagnosis of canine SLE was mainly based on the 11 diagnostic criteria for human SLE and two marked immunological features of canine SLE. Among 59 pet dogs owned by 37 SLE patients, 11 (18.64%) were ANA positive, and three (5.08%) had SLE. In contrast, of 187 pet dogs owned by non-SLE households, nine (4.81%) were ANA positive, and none (0%) had SLE. Among 650 outpatient dogs registered in the veterinary hospital, 34 (5.23%) were ANA positive, and six (0.92%) had SLE. Frequency of ANA and SLE among pet dogs owned by SLE patients was significantly higher than in pet dogs owned by non-SLE households (P = 0.001 for ANA; P = 0.013 for SLE) and in outpatient dogs (P < 0.001 for ANA; P = 0.032 for SLE). With respect to canine SLE development, the relative risk or risk ratio (R) of human SLE contact varied from 5.5 (compared with outpatient dogs) to near the infinite (compared with dogs owned by non-SLE households). The prevalence of canine SLE among pet dogs of SLE patients was therefore estimated to be 508 per 10 000 [95% confidence interval (95% CI), 0-1068]. In conclusion, pet dogs with human SLE contact were at a higher risk of developing SLE. Our results indicate that a common environmental factor or zoonotic agent may be involved in the development of human and canine SLE.

Several toxins with distinct pharmacological properties were isolated from the venom of Thailand cobra (Naja naja siamensis) by cation‐exchange chromatography. Two neurotoxins and one basic toxin with cardiotoxic activity were further purified and sequenced. The neurotoxins characterized were closely similar to the previously reported long‐ and short‐chain neutrotoxins. The complete sequences of one minor neurotoxin and one cardiotoxin analogue were determined with the automatic protein sequencer in non‐stop single runs of Edman degradation coupled with C‐terminal sequence determination with carboxypeptidase digestion. The minor neurotoxin consists of 62 amino‐acid residues with 8 cysteine residues and is found to be almost identical to cobrotoxin, a major toxic component of Formosa cobra (Naja naja atra). The sequence comparison of the 60‐residue cardiotoxin with other reported cytotoxins of snake venoms indicates that 8 cysteine residues at the positions 3, 14, 21, 38, 42, 53, 54, and 59 are invariant among all sequences, with only two conservative changes at other positions along the sequence. The upshot of this report exemplified the facile sequence analysis of venom toxins by the application of pulsed‐liquid phase protein sequencer and also revealed new analogues of a minor neurotoxin and one major cardiotoxin reported previously on the same species of Thailand cobra.