癌症最新文献

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.

The overall survival of patients with cervical cancer has improved due to detection at an early stage and availability of comprehensive treatments in China. As patients' lives prolonged, it is important to understand their health-related quality of life (QoL) during and after treatment. We used the EQ-5D questionnaire to assess QoL of 194 patients with cervical lesions at Sichuan University West China Second Hospital between May 2010 and January 2011. Patients were surveyed before primary treatment and at 1, 3, and 6 months after primary treatment. Results showed a consistent decline in EQ-5D scores in the spectrum of cervical lesions at each time point after treatment (all P < 0.05). For patients with precursor lesions, there was an increasing trend along the timeline of treatment (P < 0.01). For patients with early-stage cervical cancer, EQ-5D scores declined in the first month (P = 0.01) and gradually increased to higher levels at 6 months post-treatment than those before treatment (P < 0.01). EQ-5D scores followed a similar trend in patients with advanced cervical cancer (P = 0.04), though they did not statistically rebound after 6 months (0.84 ± 0.19 vs. 0.86 ± 0.11, P = 0.62). Regarding advanced cervical cancer, EQ-5D scores for women above 40 years of age appeared to recover more rapidly and reached higher levels than those for women below 40 years (P = 0.03). Caution and extra care are recommended in the early period of cervical cancer treatment given the slight deterioration in the QoL, and in particular, for younger cervical cancer patients. Our study implies that health care providers may need to improve the health-related QoL of cervical cancer patients.

Chylothorax is a rare complication of neck dissection, and bilateral chylothorax is even rarer. However, both are potentially serious and sometimes life-threatening, especially those that are associated with left neck dissection for head and neck neoplasms. We report one case of bilateral chylothorax following left supraclavicular dissection for breast cancer. This case was treated successfully with a new conservative management approach.

Laparoscopic techniques have been extensively used for the surgical management of colorectal cancer during the last two decades. Accumulating data have demonstrated that laparoscopic colectomy is associated with better short-term outcomes and equivalent oncologic outcomes when compared with open surgery. However, some controversies regarding the oncologic quality of mini-invasive surgery for rectal cancer exist. Meanwhile, some progresses in colorectal surgery, such as robotic technology, single-incision laparoscopic surgery, natural orifice specimen extraction, and natural orifice transluminal endoscopic surgery, have been made in recent years. In this article, we review the published data and mainly focus on the current status and latest advances of mini-invasive surgery for colorectal cancer.

There have been many clinical trials conducted to evaluate novel systemic regimens for unresectable pancreatic cancer. However, most of the trial results were negative, and gemcitabine monotherapy has remained the standard systemic treatment for years. A number of molecular targeted agents, including those against epidermal growth factor receptor and vascular endothelial growth factor receptors, have also been tested. In recent years, there have been some breakthroughs in the deadlock: three regimens, namely gemcitabine-erlotinib, FOLFIRINOX, and gemcitabine-nab-paclitaxel, have been shown to prolong the overall survival of patients when compared with gemcitabine monotherapy. In addition, emerging data suggested that the membrane protein human equilibrative nucleotide transporter 1 is a potential biomarker with which to predict the efficacy of gemcitabine. Here we review the literature on the development of systemic agents for pancreatic cancer, discuss the current choices of treatment, and provide future directions on the development of novel agents.

Ovarian cancer is the leading cause of death in women worldwide. Cisplatin is the core of first-line chemotherapy for patients with advanced ovarian cancer. Many patients eventually become resistant to cisplatin, diminishing its therapeutic effect. MicroRNAs (miRNAs) have critical functions in diverse biological processes. Using miRNA profiling and polymerase chain reaction validation, we identified a panel of differentially expressed miRNAs and their potential targets in cisplatin-resistant SKOV3/DDP ovarian cancer cells relative to cisplatin-sensitive SKOV3 parental cells. More specifically, our results revealed significant changes in the expression of 13 of 663 miRNAs analyzed, including 11 that were up-regulated and 2 that were down-regulated in SKOV3/DDP cells with or without cisplatin treatment compared with SKOV3 cells with or without cisplatin treatment. miRNA array and mRNA array data were further analyzed using Ingenuity Pathway Analysis software. Bioinformatics analysis suggests that the genes ANKRD17, SMC1A, SUMO1, GTF2H1, and TP73, which are involved in DNA damage signaling pathways, are potential targets of miRNAs in promoting cisplatin resistance. This study highlights candidate miRNA-mRNA interactions that may contribute to cisplatin resistance in ovarian cancer.

Previous studies suggested that smoking and passive smoking could increase the risk of breast cancer, but the results were inconsistent, especially for Chinese females. Thus, we systematically searched cohort and case-control studies investigating the associations of active and passive smoking with breast cancer risk among Chinese females in four English databases (PubMed, Embase, ScienceDirect, and Wiley) and three Chinese databases (CNKI, WanFang, and VIP). Fifty-one articles (3 cohort studies and 48 case-control studies) covering 17 provinces of China were finally included in this systematic review. Among Chinese females, there was significant association between passive smoking and this risk of breast cancer [odds ratio (OR): 1.62; 95% confidence interval (CI): 1.39-1.85; I2 = 75.8%, P < 0.001; n = 26] but no significant association between active smoking and the risk of breast cancer (OR: 1.04; 95% CI: 0.89-1.20; I2 = 13.9%, P = 0.248; n = 31). The OR of exposure to husband's smoking and to smoke in the workplace was 1.27 (95% CI: 1.07-1.50) and 1.66 (95% CI: 1.07-2.59), respectively. The OR of light and heavy passive smoking was 1.11 and 1.41, respectively, for women exposed to their husband's smoke (< 20 and ≥ 20 cigarettes per day), and 1.07 and 1.87, respectively, for those exposed to smoke in the workplace (< 300 and ≥ 300 min of exposure per day). These results imply that passive smoking is associated with an increased risk of breast cancer, and the risk seems to increase as the level of passive exposure to smoke increases among Chinese females. Women with passive exposure to smoke in the workplace have a higher risk of breast cancer than those exposed to their husband's smoking.

The survival of most patients with both unresectable hepatic and pulmonary metastases of colorectal cancer is poor. In this retrospective study, we investigated the efficacy of computed tomography (CT)-guided radiofrequency ablation (RFA) and systemic chemotherapy plus hepatic artery infusion of floxuridine (HAI-FUDR). Sixty-one patients were selected from 1,136 patients with pulmonary and hepatic metastases from colorectal cancer. Patients were treated with RFA and systemic chemotherapy plus HAI-FUDR (ablation group, n = 39) or systemic chemotherapy plus HAI-FUDR (FUDR group, n = 22). Patients in the two groups were matched by sex, age, number of metastases, and calendar year of RFA or FUDR. Survival data were evaluated by using univariate and multivariate analyses. Clinical characteristics were comparable between the two groups. All patients in the ablation group underwent RFA and chemotherapy. Median follow-up was 56.8 months. The 1-, 3-, and 5-year overall survival (OS) rates were 97%, 64%, and 37%, respectively, for the ablation group, and 82%, 32%, and 19%, respectively, for the FUDR group. The 1-, 3-, and 5-year survival rates after metastasis were 97%, 49%, and 26% for the ablation group, and 72%, 24%, and 24% for the FUDR group, respectively. The median OS times were 45 and 25 months for the ablation and FUDR groups, respectively. In the multivariate analysis, treatment allocation was a favorable independent prognostic factor for OS (P = 0.001) and survival after metastasis (P = 0.009). These data suggest that the addition of RFA to systemic chemotherapy plus HAI-FUDR improves the survival of patients with both unresectable hepatic and pulmonary metastases from colorectal cancer.

Using a population-based cancer registry, Thuret et al. developed 3 nomograms for estimating cancer-specific mortality in men with penile squamous cell carcinoma. In the initial cohort, only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage. To generalize the prediction models in clinical practice, we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery. Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008. The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade. Discrimination, calibration, and clinical usefulness were assessed to compare model performance. The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging (Harrell's concordance index = 0.817 and 0.832, respectively), whereas it was inferior for the Surveillance, Epidemiology and End Results staging (Harrell's concordance index = 0.728). Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade, which also achieved favorable clinical net benefit, with a threshold probability in the range of 0 to 42%. The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery. Our data support the integration of this model in decision-making and trial design.

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus formation in the main vasculature is extremely poor. Sorafenib combined with transarterial chemoembolization is a novel treatment approach for advanced HCC. In this study, we report two HCC patients with inferior vena cava tumor thrombus who underwent the combination treatment. The overall survival times for these two patients were 44 months and 35 months, respectively. Our report suggests that sorafenib combined with transarterial chemoembolization may be a viable choice for patients with advanced HCC even with inferior vena cava tumor thrombus. Further studies are required to verify the efficacy and safety of this combination therapy for patients with advanced HCC with inferior vena cava tumor thrombus.