Sunitinib malate as first-line treatment for an advanced, poorly differentiated pancreatic neuroendocrine tumor.

Pancreatic neuroendocrine tumors (PNETs) are rare, accounting for approximately 2% of primary malignant tumors of the pancreas. Compared with common pancreatic ductal adenocarcinomas, they grow more slowly, are less invasive and have a better prognosis. At present, surgery is the preferred method of treatment of PNETs, and offers the only chance of a cure. However, owing to the occult onset of PNETs, once diagnosed they are often inoperable when the diagnosis is established, and the optimal treatment of patients with inoperable liver metastases remains uncertain. In recent years, targeted drug therapies have emerged and have proved effective in prolonging progression-free survival in patients with advanced well-differentiated PNETs, but hardly any progress has been made in the treatment of poorly differentiated PNETs. In the patient described in this report, who had a poorly differentiated PNET with multiple hepatic metastases and had refused cytotoxic chemotherapy, oral sunitinib malate treatment for 22 months with regular follow-ups proved tolerable and effective in significantly reducing the size of the intrahepatic masses.

Mitochondrial DNA somatic mutations are frequent in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China, and is highly sensitive to radiotherapy. The control region (D-loop) of mtDNA is a polymorphic region in which point mutations occur frequently. In this study, point mutation and common deletion (CD) mutations were investigated in 23 samples of NPC tumor tissue and in the radiation-treated NPC cell line CNE2. Polymorphisms at 72 (7.28%, 72/988) nucleotide positions in D-loop region and 6 (0.75%, 6/795) nucleotide positions in part of the functional gene encoding regions were detected in all NPC patients. Of the detected polymorphisms, 8 are novel. These variants are nonencoding transitions, including np292T-->C , np517G-del, np16038A-->G, np513G-del, np16242C-->A, np513G-del, np16242C-->A and np15787T-->C transition. A total of 39 point mutations in the D-loop region of mtDNA were detected in 43.5% (10/23) of the NPC patients. Three point mutations in the functional gene encoding regions of mtDNA were detected in only 8.7% (2/23) of NPC patients. The effect of he mutation at np709G-->A in the 12sRNA gene is unclear, and the A-->G substitution at np15769 in the cytochrome B gene is a synonymous mutation. The C-->T substitution at np15970 in the T Psi C loop of the tRNA(pro) gene could alter the position of the proline residue. After irradiation, the survival fraction of CNE2 cells decreased as X-ray dose increased. Moreover, X-ray radiation could induce apoptosis and the CD mutation in a time- and dose-dependent manner, but did not induce mtDNA point mutations. A positive correlation between the apoptosis index and the ratio of CD/WT mtDNA was observed in irradiated CNE2 cells. Our results suggest that CD mutation induced by irradiation is one of the late events after apoptosis of the cancer cells, and the mtDNA CD mutation may associated with the susceptibility of NPC cells to IR-induced apoptosis.