OBJECTIVETo explore the possibility of further improvement of the efficacy of neoadjuvant chemoradiotherapy in locally advanced lower rectal cancer and the management of patients with clinical complete regression.

METHODSFrom May 2001 to August 2007, 192 cases with locally advanced lower rectal cancer (T3/T4 or N(+)) received preoperative radiotherapy 40 - 46 Gy/20 - 23 fractions and concomitant oral capecitabine 625 mg/m(2) bid for 10 weeks prior to surgery. Curative resection with total mesorectal excision (TME) was carried out 6 weeks after the end of radiation.

RESULTSAs a result, 117 cases (60.9%) experienced adverse events but only 2 suffered from G3 side effects. Seventeen cases (8.9%) had a clinical complete tumor regression without surgery; 175 patients underwent curative resection, of them 134 cases with low anterior resection (LAR), 32 cases with ultra-low anterior resection with Park's coloanal anastomosis (6 cases with diverting temporary colostomy) and 9 cases with abdominal pelvic resection (APR). Sphincter preservation was achieved in 94.9%. Twenty-four patients (12.5%) got pathological complete response (CR), 17 patients with clinical CR and the overall CR rate was 21.4%. According to the pathological staging post operation: T0N0 41 cases, T2N0 43 cases, T3N0 77 cases, T4N0 5 cases, T2N1 11 cases, T3N1 13 cases, T4N1 2 cases; Graded under Dworak's tumor regression: TRG0 8 patients, TRG1 32 patients, TRG2 28 patients, TRG3 83 patients and TRG4 24 patients, with an overall pathological tumor downstaging in 77.14%. No operative death occurred, 5 patients suffered from rectovaginal fistulas and 4 anastomotic leakages with an overall anastomotic leakage rate of 5.1% (9/175) and all the patients recovered uneventfully after properly managed. All patients were followed up for a median time of 42 months (range, 12 - 87 months). During the time, 11 patients developed lung metastases, 6 liver metastases and 7 had local recurrences. The 3 years disease-free survival (DFS) was 86.6% and overall survival (OS) was 92.6%.

CONCLUSIONSNeoadjuvant chemoradiotherapy has high efficacy in locally advanced lower rectal cancer, resulting in tumor down-staging, improved resectability and sphincter preservation, and reduced local recurrences. Meanwhile the cases with clinical complete response can be followed up closely and safely without surgery.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Rectal Neoplasms ; drug therapy ; radiotherapy ; Treatment Outcome

OBJECTIVETo study the effects of integrin beta1 on the chemotaxis of hepatocellular carcinoma (HCC) cells to laminin (LN).

METHODSA micropipette technique was adopted to investigate the effect of integrin beta1 blockade on pseudopod protrusion of HCC cells in response to LN stimulation. Chemotactic pseudopod protrusion of a HCC cell was evaluated using a dual-pipette set-up, in which two pipettes filled with LN solution were positional in close contact with the same cell, and pseudopod protrusion into each pipette was viewed dynamically and recorded with a tape recorder. The lengths of pseudopods were measured, then plotted against time to obtain a pseudopod growth curve. The integrin beta1 subunit on the surfaces of HCC cells was analyzed by flow cytometry.

RESULTSIn dual pipette chemotaxis experiment, when the two pipettes were filled with LN (50microg/ml, 200microg/ml), pseudopods extended from the HCC cells into each of the pipettes nearly symmetrically. Upon addition of anti-CD29 (20microg/ml) to one of the pipettes, the pseudopod protrusion was blocked almost completely, while the pseudopod protrusion into the opposite pipette became more evidently, with larger maximum length. The expression rate of integrin beta1 on the cells was up to 95.78%.

CONCLUSIONIntegrin beta1 subunit is the important receptor for mediating HCC cells chemotaxis to laminin.

Carcinoma, Hepatocellular ; pathology ; Cell Adhesion ; Cell Line, Tumor ; Chemotaxis ; Humans ; Integrin beta1 ; immunology ; metabolism ; physiology ; Laminin ; metabolism ; Liver Neoplasms ; pathology

Objective To investigate the associations between normal serum uric acid (UA) levels and knee symptoms and structural changes in patients with knee osteoarthritis (OA).Methods A total of 205 patients with knee OA were enrolled. According to the inclusion and exclusion criteria, 122 patients with OA were included in the study. The general condition of patients were investingated. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess severity of the knee joint symptoms. The Kellgren-Lawrence (K-L) grading system was used to assess radiological severity of the knee joint. Osirix software was used to assess changes of knee structure in magnetic resonance imaging (MRI). Peroxidase method was used to measure the serum levels of uric acid. Patients with normal range of uric acid were included in the study.Results The patients with lower levels of UA (split at the median level, 263 μmol/L) had a higher proportion of women, lower height, weight and lower proportions of K-L grade≥2. After adjustment for sex, age and body mass index, serum UA was negatively associated with total WOMAC scores (β=-16.15, P=0.018), WOMAC pain (β=-3.15, P=0.037), and WOMAC stiffness (β=-1.65, P=0.025). However, there were no significant associations between serum UA levels and knee joint structure changes.Conclusions In OA patients with normal serum UA, serum UA is negatively associated with the severity of joint symptoms, suggesting that UA within normal range may play a protective role in OA symptoms.