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Dave Martin, Associated Press
CORRECTS NAME OF PLAYER - Connecticut guard Jeremy Lamb reacts near the end of the team's 77-64 loss to Iowa State in an NCAA men's college basketball tournament second-round game in Louisville, Ky., Thursday, March 15, 2012.

LOUISVILLE, Ky. — Several seconds were left on the clock and Connecticut still had one last possession.

Jim Calhoun had seen more than enough, however. Leaving his seat before the final buzzer, he walked to the scorer's table to exchange a quick handshake with Iowa State coach Fred Hoiberg and then was gone.

Maybe for good.

Connecticut became the first defending national champion to lose its opening game since UCLA in 1996, its 77-64 loss to Iowa State on Thursday night one last disappointment in a season filled with them.

"We're talking about tonight's game. We're not talking about me," Calhoun said curtly. "I'm going to get on the plane tomorrow, go home and do what I usually do and meet up with the team on Monday. My own personal thing, I don't think it has any relevance, to be honest with you."

Oh, but it does.

Calhoun is synonymous with UConn, the architect of three national titles with the Huskies and 855 career victories. But he turns 70 in May, and the back problems that forced him to take a one-month leave of absence were yet one more health crisis for the three-time cancer survivor. He has said he did not retire last year in large part because he wanted to see through NCAA sanctions that resulted from recruiting violations in his program.

Calhoun had to sit out the first three games of the Big East season, and didn't want another coach to serve that penalty. Now, the team faces a possible banishment from the 2013 NCAA tournament — and maybe longer — because of past academic problems.

"There were some things that made me feel good about this team," Calhoun said. "I like coaching basketball, I hate this ending."

In other games in Louisville: overall No. 1 seed Kentucky routed Western Kentucky 81-66; third-seeded Marquette held off 14th-seeded BYU 88-68; and sixth-seeded Murray State outran 11th-seeded Colorado State 58-41.

NCAA investigations and questions about Calhoun's future have hung over UConn all year. In addition to Calhoun's suspension at the start of the Big East season, freshman Ryan Boatright missed nine games after an NCAA investigation found he and his family took more than $8,000 in impermissible benefits before he enrolled at Connecticut.

Connecticut withstood the turmoil until January, when things unraveled in spectacular fashion and with dizzying speed. The Huskies lost 11 of 16, including three of five when Calhoun was out. Among the losses? A 21-point blowout at Louisville and an 18-point loss to Syracuse five days later.

"Effort and attitude," Shabazz Napier said when asked to explain what went wrong this year. "We had a great player last year who brought it every single day. And as a point guard, it's my job to bring that. When you don't bring that effort and attitude to be that leader for your teammates, you lose games. More often than not, you sit up here talking about what you could have done and what you should have done."

Take Thursday's game.

After trailing by as many as 22 points in the first half, UConn (20-14) cut the lead to 58-52 with 8:24 to play after three straight baskets by Boatright.

"Once we cut it to six, I felt like if we dug down a little deeper maybe it would crack," Boatright said.

But the Huskies couldn't get any closer, missing their next four shots and going scoreless for more than 5½ minutes.

Iowa State (23-10), meanwhile, got a big layup from Bubu Palo and an even bigger bucket from Chris Allen.

Allen has played more NCAA tournament games than any player in the 68-team field after making back-to-back Final Fours with Michigan State in 2009 and 2010, and his experience showed. He chased down his miss on a 3 from the corner and went up and under the basket, scoring to put Iowa State back in front 63-52 with 4:15 to play.

UConn could never make another run, and the Cyclones scored their last 14 points at the free throw line. Royce White had a double-double with 15 points and 13 rebounds, and Iowa State had a whopping 41-24 edge in rebounds.

Napier led the Huskies with 22, and Jeremy Lamb had 19.

"I feel like just we wanted it more," said Allen, who led Iowa State with 20 points. "I felt like we was doing everything we needed to and played hard."

The eighth-seeded Cyclones now face Kentucky, which was never seriously threatened by the Hilltoppers (16-19). Terrence Jones had 22 points and 10 rebounds, and Doron Lamb added 16 points for Kentucky. Freshman and player of the year candidate Anthony Davis added 16 points, nine rebounds and seven blocks for Kentucky, which improved to 33-2.

"For this to be the first NCAA game for us, freshmen are usually — well I know I was last year — just a little nervous about all the pressure put on us, and it wasn't even as much pressure last year as it is this year," Jones said. "I just wanted to tell everybody to have fun and run. We just got going from there."

After leading by as many as 19 points in the first half, Marquette saw its lead dwindle to 52-46 with 15:26 to play. But Darius Johnson-Odom and Jae Crowder came up with one big shot after another, and the Cougars couldn't duplicate their big comeback in the First Four. Cheered on by a vocal home crowd, Murray State (31-1) broke the game open with an 18-2 run in the second half.

Isaiah Canaan had 15 points and Donte Poole added 13 despite breaking his nose when he took an inadvertent elbow to the face.

"As long as we won," Poole said, "I'm fine."