Ring-Contracted Artemisinin Derivatives as Novel CDK 4/6 Inhibitors: Synthesis and Anti-Breast Cancer Evaluation.

The endoperoxide group of artemisinins is universally accepted an essential group for their anti-cancer effects. In this study, a series of D-ring-contracted artemisinin derivatives were constructed by combining ring-contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty-six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H-NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 µM and 9.97±1.44 µM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 µM, and its activity was approximately 1/3 of the positive control Palbociclib.

Endolymphatic sac tumor: case report and review of the literature.

Endolymphatic sac tumor (ELST) is a rare neoplasm which can be encountered sporadically or in Von Hippel-Lindau (VHL) disease. Here we report a sporadic case of ELST in 31-year-old man. Neither the symptoms nor a family history of VHL disease were found in the patient. CT imaging demonstrated an expansile lytic lesion of the mastoid process of the left petrous bone. MR scanning revealed a 5.2 cm × 4.7 cm × 4.2 cm mass which showed hyperintensity on T1- and T2-weighted images. Histologic sections showed a papillary, cystic or glandular architecture. The papillary and glandular structures were lined by a single layer of flattened cuboidal-to-columnar cells. The stroma of the papillary fronds was richly vascularized and chronically inflamed. The tumor showed diffusely positive reactivity with cytokeratin (Pan), cytokeratin 19, cytokeratin 5/6, cytokeratin 7, EMA, vimentin, CD56, and NSE and also showed variable reactivity with glial fibrillary acidic protein (GFAP) and VEGF. The Ki-67 immunostain showed a proliferation index of < 1%. Because the mass was large, it was difficult to extirpate surgically. After surgery, the patient underwent gamma-knife radiosurgery for residual tumor. The findings indicate that ELST is a rare neoplasm with benign histopathological appearance and clinically destructive behavior. Because of the rarity of this tumor, it can easily be confused with other tumors such as paraganglioma, middle ear adenoma, adenocarcinoma, papillary carcinoma of thyroid or choroid plexus papilloma. Owing to its locally aggressive nature, it is difficult to extirpate surgically when it is large. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7973320646763012.

Association between polymorphisms of XRCC1 Arg399Gln and XPD Lys751Gln genes and prognosis of colorectal cancer in a Chinese population.

We conducted this study to detect associations between XRCC1 Arg399Gln and XPD Lys751Gln genotypes and survival of colorectal cancer patients treated with 5-FU/oxalipatin chemotherapy. We included 289 Chinese patients with advanced colorectal cancer, who had received 5-FU/oxalipatin chemotherapy as first-line treatment from January 2005 to January 2007. All patients were followed up till Nov. 2011. Genotyping for XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms was based upon duplex polymerase-chain-reaction with the PCR-RFLP method. In our study, we found the XRCC1 399 Gln/Gln genotype to confer significantly higher rates of response to chemotherapy when compared to the Arg/Arg genotype [OR (95% CI)=2.56(1.57-2.55)]. patients with the XPD 751 Gln/Gln genotype had significantly higher rates of response to chemotherapy [OR (95% CI)=1.54(0.87-2.65)] and those with the XRCC1 399 Gln/Gln genotype had a longer average survival time and significantly lower risk of death than did those with the Arg/Arg genotype [HR (95% CI)=0.66(0.36-0.95)]. Similarly, those carrying the XPD 751Gln/Gln genotype had 0.51-fold the risk of death of those with XPD 751Lys/Lys [HR (95% CI)=0.51(0.33-0.94)]. In conclusion, it is suggested that the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms should be routinely assessed to determine colorectal patients who are more likely to benefit from 5-FU/oxalipatin chemotherapy.

Regulation of hypoxia-induced mRNA expressions of HIF-1alpha and osteopontin and in vitro radiosensitization by tirapazamine in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells.

BACKGROUND AND OBJECTIVE: Combined hypoxic cytotoxic drugs and chemoradiotherapy is an important mean of oncotherapy, and Tirapazamine (TPZ) is one of the most remarkable drugs. It has been shown that TPZ has a synergistic effect with radiotherapy on tumor cells, but whether TPZ would down-regulate the expression of the hypoxia-induced genes has not been reported. This study was to investigate the hypoxia-induced mRNA expressions of hypoxia inducible factor-1alpha (HIF-1alpha) and osteopontin (OPN) in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells and the radiosensitization of TPZ, a hypoxia-specific drug, on HNE-1 and CNE-1 cells in vitro. METHODS: The IC50 values of TPZ for HNE-1 and CNE-1 cells were measured using MTT assay, and the mRNA expressions of HIF-1alpha and OPN in HNE-1 and CNE-1 cells was determined using RT-PCR under aerobic and hypoxic conditions, respectively. The survival rates of HNE-1 and CNE-1 cells treated with or without TPZ at IC10 in the presence or absence of oxygen for 6 h were determined using colony formation assay following exposure to 1-6 Gy of 60Co radiation. The dose-survival curves were plotted and the values of D0, Dq and SER were calculated as a single-hit multitarget model. RESULTS: The IC50 values of TPZ were 34.81 µmol/L and 35.02 µmol/L in HNE-1 and CNE-1 cells under aerobic condition, and 30.20 µmol/L and 28.48 µmol/L under hypoxic condition, respectively. The expressions of HIF-1alpha and OPN mRNA were reduced by TPZ in HNE-1 cells, but not in CNE-1 cells under hypoxic condition. For the HNE-1 cells, the respective values of D0 and Dq were 0.89 Gy and 0.28 Gy following normoxic irradiation versus 1.47 Gy and 0.44 Gy following hypoxic irradiation. For the CNE-1 cells, the respective values of D0 and Dq were 0.72 Gy and 0.68 Gy following normoxic irradiation versus 0.95 Gy and 0.56 Gy following hypoxic irradiation. The values of D0 and Dq for HNE-1 and CNE-1 cells treated with TPZ under hypoxic condition following irradiation were 0.66 Gy, 0.21 Gy and 0.85 Gy, 0.79 Gy, respectively. CONCLUSION: TPZ can down-regulate hypoxia-induced expression of HIF-1alpha and OPN mRNA of HNE-1 cells and radiosensitize the HNE-1 cells but not CNE-1 cells, and act as a hypoxia modifier.

[Comparative study on long-term results of laparoscopic and open radical resection for colorectal carcinoma].

OBJECTIVE: To compare the long-term results of laparoscopic and open radical resection for colorectal carcinoma. METHODS: Two hundred and fifteen patients with colorectal cancer from January 1996 to September 2000 were non-randomly divided into laparoscopic and open operation groups. Local recurrence, distant metastasis, 5-year survival rate and long-term postoperative complications were compared between the two groups. RESULTS: Eighty-seven cases received laparoscopic resection and 128 cases received open operation. There were no statistical differences in age, sex and tumor stage between the two groups (P > 0.05). The 5-year-survival rate was 70% in open operation group, and 78% in laparoscopic group (P > 0.05). There were no significant differences in the incidences of local recurrence, distant metastasis, incision seeding, and incision hernia between the two groups (P > 0.05). The complication rate of postoperative adhesive intestinal obstruction was significantly lower in laparoscopic group than that in open operation group (P< 0.05). CONCLUSIONS: Long-term results of laparoscopic resection are similar to those of open resection for colorectal carcinoma, but laparoscopic surgery has less long-term complications.

[Comparison of ultrasound-guided mammotome and Tru-cut biopsy needle in diagnosing breast masses].

OBJECTIVE: To compare the diagnostic value of ultrasound-guided mammotome and Tru-cut biopsy needle in diagnosing breast masses. METHODS: Retrospective analysis was performed in 214 patients with breast masses obtained separately by mammotome or Tru-cut biopsy needle guided by ultrasound, and analyzed by pathological examination. The success ratios of sample choosing and the coincident ratios of pathological diagnosis were compared. RESULTS: The success ratios of sample choosing for mammotome and Tru-cut biopsy needle were 100% and 90%, respectively. The coincident ratios of pathological diagnosis of mammotome and Tru-cut were 98. 7% and 90%, respectively. There was significant difference in the 2 groups (P < 0.05). CONCLUSION: Mammotome is a useful method and superior to Tru-cut biopsy needle in the diagnosis of breast masses.