Mn-SOD antisense upregulates in vivo apoptosis of squamous cell carcinoma cells by anticancer drugs and gamma-rays regulating expression of the BCL-2 family proteins, COX-2 and p21.

ROIs and their scavengers are associated with apoptosis induction by anticancer drugs and gamma-rays, but the details have not been clarified. We examined the effect of transfection of Mn-SOD antisense on apoptosis by 5-FU, PLM, CDDP and gamma-rays using nu/nu mice. After inoculation of Mn-SOD antisense-transfected SCC cells into the subcutis of each mouse's back, they slowly multiplied to form tumors sized 1,460 +/- 70 mm(3) at day 60, while control vector-transfected SCC cells rapidly multiplied, with a mean tumor size of 2,330 +/- 220 mm(3). Inversely, mice in the Mn-SOD antisense group survived longer (mean survival duration 94.4 +/- 12.7 days) compared to those in the empty vector group (67.3 +/- 6.8 days). After treatment with 5-FU (5 microg/day), PLM (50 microg/day), CDDP (10 microg/day) and gamma-rays (2 Gy/day), mean survival times were largely prolonged, to 126.3 +/- 22.7, 123.0 +/- 22.1, 136.3 +/- 24.0 and 143.0 +/- 20.8 days, respectively, while mean survival times in the empty vector group were 91.7 +/- 14.8, 85.7 +/- 13.3, 97.5 +/- 16.0 and 100.7 +/- 17.1 days, respectively. Immunohistologically, tumors in the Mn-SOD antisense group revealed additional nick end-labeled cells compared to those in the empty vector group. In comparison, strong expression of Bax, Bak and p21(waf1/cip1) and suppressed expression of Bcl-2, Bcl-X(L) and COX-2 were observed in the Mn-SOD antisense group and the expression pattern of these proteins was the inverse in the empty vector group. The increased expression of these proapoptotic proteins appeared to be p53-independent because p53 protein expression was not increased in the antisense group. These immunohistologic results were supported by Western blotting of each protein. In conclusion, Mn-SOD antisense transfection is advantageous for apoptosis induction of SCC cells by anticancer drugs and gamma-rays through induction of proapoptotic Bcl-2 family proteins and suppression of antiapoptotic protein expression.

Diagnostic value of cervical somatosensory evoked potentials recorded from the intervertebral discs after median and ulnar nerve stimulation in cervical spondylotic myelopathy.

We have studied the cervical somatosensory evoked potentials (CSEPs) recorded referentially from serial intervertebral discs after stimulation of the median nerve or the ulnar nerve at the wrist in cervical spondylosis. In seven unilateral radiculopathies, the CSEPs evoked by stimulation on the asymptomatic side normally consisted of the P1-N1 and the P2-N2 components, which represented the potentials arising from the white matter and the gray matter, respectively. Of 21 myelopathies, the CSEPs revealed the white matter involvement with conduction block identified by abrupt P1-N1 amplitude reduction in 7, the gray matter involvement identified by P2-N2 amplitude reduction in 3, or a combination of both in 11. The CSEPs were useful not only for determining the level responsible for myelopathy but also for localizing the lesion in the transverse plane of the spinal cord.