In vivo growth of subclones derived from Lewis lung carcinoma is determined by the tumor microenvironment.

Heterogeneity is a fundamental feature of human tumors and plays a major role in drug resistance and disease progression. In the present study, we selected single-cell-derived cell lines (SCDCLs) derived from Lewis lung carcinoma (LLC1) cells to investigate tumorigenesis and heterogeneity. SCDCLs were generated using limiting dilution. Five SCDCLs were subcutaneously injected into wild-type C57BL/6N mice; however, they displayed significant differences in tumor growth. Subclone SCC1 grew the fastest in vivo, whereas it grew slower in vitro. The growth pattern of SCC2 was the opposite to that of SCC1. Genetic differences in these two subclones showed marked differences in cell adhesion and proliferation. Pathway enrichment results indicate that signal transduction and immune system responses were the most significantly altered functional categories in SCC2 cells compared to those in SCC1 cells in vitro. The number and activation of CD3+ and CD8+ T cells and NK cells in the tumor tissue of tumor-bearing mice inoculated with SCC2 were significantly higher, whereas those of myeloid cells were significantly lower, than those in the SCC1 and LLC1 groups. Our results suggest that the in vivo growth of two subclones derived from LLC1 was determined by the tumor microenvironment rather than their intrinsic proliferative cell characteristics.

SLC18A3 promoted renal cancer development through acetylcholine/cAMP signaling.

Renal cancer displays a high metastatic potential and a poor response to chemotherapy. However, the critical contributors to renal cancer development remain elusive. This study focused on acetylcholine (ACh) signaling. We identified the vesicular acetylcholine transporter (SLC18A3) that upregulates in patients with renal cancer. We further discovered that SLC18A3 enhanced the uptake of ACh, a classical neurotransmitter mediating synaptic transmission. The elevated ACh activated the protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathway, which contributed to renal cancer cell proliferation and invasive migration. Consistently, SLC18A3 overexpression caused sustained tumor growth and increased lung metastases in A489-bearing mice. In summary, our study demonstrated that SLC18A3 contributed to cancer spread in an ACh/PKA/CREB-dependent manner, which may drive the design of efficacious treatment strategies.

[Repair of concurrent skin and nerve defect at palm and carpal on ulnar side with free medial plantar flap].

OBJECTIVE: To explore a new method for repair of concurrent skin and nerve defect at palm and carpal on ulnar side. METHODS: From April 2000 to August 2009, five cases with concurrent skin and nerve defect at palm and carpal on ulnar side were reconstructed with free medial plantar flaps. Palmar nervous proprii defect at ulnar side of little finger was repaired by the first toe tibia nervous proprii in one case. The superficial branch of radial nerve was applied to repair the defect of ulnar nerve, as well as its deep or superficial branch in two cases. The superficial branch of radial nerve was also used to repair the defect of superficial branch of ulnar nerve, common palmar digital nerve of the fourth finger, Little finger ulnar palmar nervous proprii in one case. The dorsal branch of ulnar nerve was applied to repair the defect of superficial branch of ulnar nerve, common palmar digital nerve of the fourth finger, little finger ulnar palmar nervous proprii in one case. The vascular bundle of medial plantar flap was anastomosed with ulnar vascular bundle. The wounds at donor sites were covered with free skin grafts which were obtained from upper leg. RESULTS: All the flaps and skin grafts were survived completely. The five patients were followed up for six months to four years with no muscular atrophy or claw hand deformity. The esthetic result was satisfied. The Sensory of flaps and fingers recovered to S3 to S3+. The two-point discrimination distance on flaps was range from 7 mm to 10 mm. The postoperative comprehensive evaluation was excellent in the cases whose superficial and deep branches of ulnar nerve were repaired. CONCLUSIONS: Free medial plantar flap is an effective method to repair concurrent skin and nerve defect at palm and carpal on the ulnar side.

[The reverse flap based on two dorsal metacarpal artery for reconstruction of degloved fingertip avulsion].

OBJECTIVE: To discuss the application of reverse flap based on two dorsal metacarpal artery for reconstruction of degloved fingertip avulsion. METHODS: From Jan. 2005 to Mar. 2008, 28 cases with degloved fingertip avulsion were treated with reverse flaps based on two dorsal metacarpal artery. The defects were located distal to the distant interphalangeal joints and were 0.8-2.2 cm in length. 10 defects was in the index fingers, 13 in the middle fingers and 5 in the ring fingers. 24 fingers were treated in an emergency surgery. 4 fingers were treated due to skin necrosis. RESULTS: Epidermal necrosis happened at the distal end of flaps in 3 cases. All the other flaps survived completely. 25 cases were followed up for 4-27 months with satisfactory cosmetic and functional results. The 2-points discrimination distance was 6.0-9.0 mm (average, 7.6 mm). CONCLUSIONS: The reverse flap based on two dorsal metacarpal artery is easily performed and reliable for degloved fingertip avulsion with satisfactory results.