Recent advances in the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.

Indoleamine 2,3-dioxygenase 1 (IDO1), an important immunoregulatory enzyme ubiquitously expressed in various tissues and cells, plays a key role in tryptophan metabolism via the kynurenine pathway and has emerged as an attractive therapeutic target for the treatment of cancer and other diseases, such as Alzheimer's disease and arthritis. IDO1 has diverse biological roles in immune suppression and tumor progression by tryptophan catabolism. In addition, IDO1-mediated immune tolerance assists tumor cells in escaping the immune surveillance. Recently, extensive and enormous investigations have been made in the discovery of IDO1 inhibitors in both academia and pharmaceutical companies. In this review, IDO1 inhibitors are grouped as tryptophan derivatives, inhibitors with an imidazole, 1,2,3-triazole or tetrazole scaffold, inhibitors with quinone or iminoquinone, N-hydroxyamidines and other derivatives, and their enzymatic inhibitory activity, selectivity and other biological activities are also introduced and summarized.

[Gefitineb inhibits the growth and induces the apoptosis of mouse I-10 Leydig testicular cancer cells in vitro].

OBJECTIVE: To observe the inhibitory effect of gefitineb on the proliferation and its inducing effect on the apoptosis of mouse I-10 Leydig testicular cancer cells in vitro. METHODS: We treated I-10 Leydig testicular cancer cells of mice with gefitineb at 0, 1.25, 2.5, 5, 10, 20, and 40 µmol/L. Then we determined the inhibitory effect of gefitineb on the growth of the cells by MTT, detected their early and late apoptosis by Annexin V-FITC/propidium iodide double staining and Hoechst 33258 nuclear staining, respectively, and observed the expressions of apoptosis-related proteins Bcl-2, Bax and caspase 3/9 by Western blot. RESULTS: Compared with the blank control group, gefitineb significantly inhibited the proliferation of the I-10 cells at 10 and 20 µmol/L (P < 0.05). The survival rate of the cells was (32.4 ± 2.8)% (P < 0.01) and their early and late apoptosis rates were (26.7 ± 4.2)% and (59.33 ± 10.2)% in the 40 µmol/L group, significantly different from those in the control (P < 0.05 and P <0.01). In comparison with the blank control group, gefitineb at 10, 20, and 40 µmol/L increased the expression of pro-apoptotic protein Bax by (41.9 ± 7.1), (60.1 ± 9.8), and (69.0 ± 11.3)% (all P < 0.05), decreased that of apoptosis-inhibitory protein Bcl-2 by (50.3 ± 8.9), (63.9 ± 6.9), and (88.7 ± 13.9)% (all P < 0.05), and elevated that of the cleft proteins caspase-3 by (69.0 ± 6.9)% (P < 0.05), (71.5 ± 8.1)% (P < 0.05), and (110.9 ± 14.2)% (P < 0.01) and caspase-9 by (51.8 ± 4.9), (54.7 ± 6.7), and (43.8 ± 11.8)% (all P < 0.05). CONCLUSION: Gefitineb can increase the cytotoxicity of I-10 Leydig testicular cancer cells of mice and induce their apoptosis via the mitochondria-mediated apoptosis signaling pathway.

Effects of age, breast density and volume on breast cancer diagnosis: a retrospective comparison of sensitivity of mammography and ultrasonography in China's rural areas.

PURPOSE: Mammography has been confirmed as the only effective mode to improve the prognosis of patients with breast cancer in Western developed countries, but might not be a good choice in other areas of the world. One of the major challenges in China is to determine an optimal imaging modality for breast cancer screening. This study was designed to clarify the sensitivity of ultrasonography compared with that of mammography in rural China. METHODS: We retrospectively studied the sensitivity of mammography and ultrasonography based on 306 breast cancer patients detected by the program of "screening for cervical cancer and breast cancer" performed in Chinese rural areas between January 2009 and December 2011, and analyzed the effects of age, breast density and volume on the sensitivity. RESULTS: Stratified analysis showed that the sensitivity of breast ultrasonography was significantly higher than that of mammography in premenopausal patients (81.4% vs. 61.1%, p=0.02), in women ≤ 55 years of age (82.2% vs. 63.4%, p<0.01), in the high breast density group (American College of Radiology [ACR] levels 3-4) (85.9% vs. 60.6%, p<0.01) and in the small breast volume group (≤ 400 ml) (87.1% vs. 66.7%, p<0.01). Age had a significant effect on sensitivity of mammography (breast density and volume-adjusted odds ratio, 6.39; 95% confidence interval, 2.8-14.4 in age group > 55 compared to age group ≤ 45), but not that of ultrasonography. Neither breast density nor volume had significant effect on sensitivity of mammography or ultrasonography. CONCLUSIONS: Ultrasonography is more sensitive than mammography in detecting breast cancer in women under 55 year-old Chinese, especially in those with high-density and relatively small breasts.

Surgical treatment of thoracic esophageal carcinoma: report of 326 cases.

OBJECTIVE: To review our experience in surgical treatment of 326 cases of thoracic esophageal carcinoma. METHODS: The clinical data of 326 patients with thoracic esophageal carcinoma from January 1990 to January 2001 were analyzed retrospectively. Among the 326 patients, the lesions of 32 patients were identified in the upper thoracic segment of the esophagus, and were found in the middle segment in 213 cases with the left 81 cases having lesions in the lower segment. Left cervical esophagogastrostomy was performed through triple incision (left cervical, right thoracic and abdominal) in 79 cases. Esophagocolostomy through triple incision was performed in 5 cases. Another 156 patients received left cervical esophagogastrostomy through two incisions (left cervical and left thoracic). Supra-aorticarch esophagogastrostomy through left posterola- teral thoracotomy was performed in 53 cases, and sub-arch esophagogastrostomy through left posterolateral thoracotomy in 33 cases. RESULTS: The post-operative mortality was 1.23% (4/326), with a five-year survival rate of 35.3%. CONCLUSION: Subtotal esophagectomy combined with thorough lymph node dissection can be the first choice for thoracic esophageal carcinoma to improve the postoperative survival rate and the quality-of life-of the patients.