Association of type 2 diabetes mellitus and the risk ofcolorectal cancer： A meta-analysis and systematic review

AIM To provide a quantitative assessment of theassociation between type 2 diabetes mellitus （T2DM）and the risk of colorectal cancer （CRC）.METHODS： Systematic review was conductedthorough MEDLINE, EMBASE, Cochrane Library, and ISI Web of knowledge databases till 31st January 2014.This meta-analysis included the cohort studies thatillustrated relative risk （RR） or odds ratio estimateswith 95%CI for the predictive risk of CRC by T2DM.Summary relative risks with 95%CI were analyzed byusing an effects summary ratio model. Heterogeneityamong studies was assessed by the Cochran＇s Q and I 2statistics.RESULTS： The meta analysis of 8 finally selectedstudies showed a positive correlation of T2DM withthe risk of CRC as depicted by effects summary RRof 1.21 （95%CI： 1.02-1.42）. Diabetic women showedgreater risk of developing CRC as their effect summaryRR of 1.22 （95%CI： 1.01-49） with significant overallZ test at 5% level of significance was higher than theeffect summary RR of 1.17 （95%CI： 1.00-1.37） of menshowing insignificant Z test. The effect summary RRof 1.19 with 95%CI of 1.07-1.33 indicate a positiverelationship between DM and increased risk of CRCwith significant heterogeneity （I 2 = 92% and P -value 〈0.05）.CONCLUSION： Results from this systematic reviewand meta-analysis report that diabetic people have anincreased risk of CRC as compared to non-diabetics.

Diagnostic strategies and the incidence of prostate cancer： reasons for the low reported incidence of prostate cancer in China

We have analysed the reasons for the low reported incidence of prostate cancer in China and argue for early diagnosis and treatment of this disease. According to the 2002 database of the International Agency for Research on Cancer （IARC）, the age-standardized incidence of prostate cancer in China is 1.6/105 person years （PY）, with a mortality rate of 1.0/105 PY and mortality-to-incidence rate ratio （MR/IR） = 0.63. The MR/IR ratio of prostate cancer in China was found to be higher than the average in Asia （MR/IR = 0.57） and much higher than that in North America （MR/IR = 0.13）. These data indicate that in China most prostate cancers were in the advanced stages at the time of diagnosis, and that patients had a short survival time thereafter. In 2004, Stamey et al. reported a retrospective American study of prostate cancer for the years 1983-2003. It was shown that most cases of prostate cancer detected by prostate-specific antigen （PSA） screening were in the advanced stage at the start of this 20-year period. These early follow-up data are quite similar to the results obtained from mass PSA screening of elderly men in Changchun, China. However, after the American programmes for early diagnosis and treatment of prostate cancer were accepted, tumours were diagnosed at earlier stages. On the basis of these findings, mass screening should be performed in the whole of China using serum PSA to facilitate early diagnosis and treatment of prostate cancer.

Prostate cancer： diagnosis and staging

Prostate cancer represents an increasing health burden. The past 20 years, with the introduction of prostate-specific antigen （PSA）, has seen prostate cancer move increasingly from a condition that presented with locally advanced disease or metastases to one that is found upon screening. More is also known about the pathology ofpre-malignant lesions. Di- agnosis relies on trans-rectal ultrasound （TRUS） to obtain biopsies from throughout the prostate, but TRUS is not useful for staging. Imaging for staging, such as magnetic resonance imaging or computed tomography, still has a low accuracy compared with pathological specimens. Current techniques are also inaccurate in identifying lymph node and bony me- tastases. Nomograms have been developed from the PSA, Gleason score and clinical grading to help quantify the risk of extra-capsular extension in radical prostatectomy specimens. Improved clinical staging modalities are required for more reliable prediction of pathological stage and for monitoring of response to treatments.

Prostate cancer： an emerging threat to the health of aging men in Asia

The aim of this study was to determine and examine the possible reasons for the difference in prostate cancer incidence between Asian men and North American men by literature review. Data regarding cancer incidence and mortality were obtained from the database of the International Agency for Research on Cancer （IARC）. A literature review was conducted by studying related articles published in peer-reviewed journals such as the The New England Journal of Medicine, Journal of Clinical Oncology, A Cancer Journal for Clinicians and Asian Journal of Andrology. To evaluate the early diagnosis and survival rates, the mortality.to-incidence rate ratio （MR/IR） was calculated from the IARC data. By comparing prostate cancer data between Asian men and North American men, we found that differences in the incidence rate and MR/IR could be attributed largely to a lack of annual prostate cancer screening with serum prostate-specific antigen （PSA） in most Asian countries. It is likely that PSA screening also contributes significantly to the differences in prostate cancer mortality rates. Prostate cancer has the highest incidence rate among five common malignancies in Asian Americans. However, the MR/IR ratio of prostate cancer is the lowest among cancers. These data seem to further support the usefulness of PSA screening, even though the percentage of low risk cancers is greater in prostate cancer than in other cancers. The low incidence rate of prostate cancer does not reflect the actual statistics of this disease in Asia. The data from limited institutions in many Asian countries seem to bias the true incidence and mortality rates. To improve this situation, incorporating PSA screening for prostate cancer, as well as constructing a nationwide cancer registration system, will be helpful.

Thermogenic protein UCP1 and UCP3 expression in non- small cell lung cancer： relation with glycolysis and anaerobic metabolism

Uncoupling protein 1(UCP1)is a proton transporter/channel residing on the inner mitochondrial membrane and is involved in cellular heat production.Using immunohistochemistry,we investigated the expression of UCP1 and UCP3 in a series of 98 patients with non-small cell lung cancer(NSCLC)treated with surgery.Expression patterns were correlated with histopathological variables,prognosis,and the expression of enzymes/proteins related to cell metabolism.Bronchial epithelium did not express UCP1 or UCP3,while alveolar cells strongly expressed UCP1.In tumors,strong expression of UCP1 and UCP3 was recorded in43/98(43.8%)and 27/98(27.6%)cases,respectively.UCP1 was significantly associated with squamous cell histology(P=0.05),whilst UCP3 was more frequently overexpressed in large cell carcinomas(P=0.08),and was inversely related to necrosis(P=0.009).In linear regression analysis,UCP1 was directly related to markers of glycolysis[hexokinase(HXKII)and phosphofructokinase(PFK1)]and anaerobic glucose metabolism[pyruvate dehydrogenase kinase(PDK1)and lactate dehydrogenase(LDH5)].UCP3 was directly linked with a glucose transporter(GLUT2),monocarboxylate transporter(MCT2),glycolysis markers(PFK1 and aldolase),and with the phosphorylation of pyruvate dehydrogenase(p PDH).Kaplan-Meier survival analysis showed that UCP3 was significantly related to poor prognosis in squamous cell carcinomas(P=0.04).UCP1 and UCP3 are overexpressed in a large subgroup of non-small cell lung tumors and their expression coincides with increased glucose absorption,intensified glycolysis,and anaerobic glucose usage.Whether UCPs are targets for therapeutic interventions in lung cancer is a hypothesis that demands further investigation.

Efficacy of maximal androgen blockade versus castration alone in the treatment of advanced prostate cancer： a retrospective clinical experience from a Chinese medical centre

In this retrospective study, we evaluated and compared the efficacy and toxicities of maximal androgen blockade （MAB） versus castration alone in Chinese patients with advanced prostate cancer. From 1996 to 2004, 608 patients with advanced prostate cancer were included in the study. Patients were retrospectively divided into two groups according to different therapeutic regimens. Of the 608 patients, 300 patients were treated with MAB （castration plus nonsteroidal antiandrogens） and the remaining 308 were treated with castration alone. The 2- and 5-year overall survival rates of these patients were 73.7% and 56%, respectively. Multivariate analysis showed that, in patients with metastatic prostate cancer, MAB was associated with not only the improvement of progression-free survival （PFS） （increased by 10 months） but also a 20.6% reduction in mortality risk compared with castration alone. In contrast, the efficacy of MAB was not superior to castration alone for patients with nonmetastatic prostate cancer. Interestingly, among patients with MAB, those using bicalutamide had a longer PFS than those using flutamide; this was especially so in patients with metastatic prostate cancer. Almost all of the toxicities due to the hormone therapy were mild to moderate and manageable. To conclude, in China, hormone therapies, including MAB and castration alone, have been standard treatments for advanced prostate cancer. For patients with nonmetastatic prostate cancer, castration alone might be adequately practical and efficient. In patients with metastatic prostate cancer, however, MAB has superior efficacy over castration alone. It is clear that MAB should be considered the first-line standard treatment for patients with metastatic prostate cancer.

Gastric cancer： current and evolving treatment landscape

Gastric(including gastroesophageal junction) cancer is the third leading cause of cancer-related death in the world.In China,an estimated 420,000 patients were diagnosed with gastric cancer in 2011,ranking this malignancy the second most prevalent cancer type and resulting in near 300,000 deaths.The treatment landscape of gastric cancer has evolved in recent years.Although systemic chemotherapy is still the mainstay treatment of metastatic disease,the introduction of agents targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor/vascular endothelia growth factor receptor has brought this disease into the molecular and personalized medicine era.The preliminary yet encouraging clinical efficacy observed with immune checkpoint inhibitors,e.g.,anti-programmed cell death protein 1/programmed death-ligand 1,will further shape the treatment landscape for gastric cancer.Molecular characterization of patients will play a critical role in developing new agents,as well as in implementing new treatment options for this disease.

Immunotherapy and therapeutic vaccines in prostate cancer： an update on current strategies and clinical implications

In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleuceI-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit.

Use of androgen deprivation therapy in prostate cancer： indications and prevalence

Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.

Intermittent tri-weekly docetaxel plus bicalutamide in patients with castration-resistant prostate cancer： a single-arm prospective study using a historical control for comparison

Whether continuous docetaxel （DTX） chemotherapy offers an advantage over intermittent therapy for castration-resistant prostate cancer （CRPC） is unknown. In this study, we evaluated the efficacy, toxicity and quality of life （QoL） of intermittent tri-weekly DTX with bicalutamide in CRPC. Forty-two patients （group A） with CRPC were enrolled. The patients received intravenous DTX （75 mg m^-2） once tri-weekly with oral bicalutamide （50 mg） once daily. Patients had a DTX holiday when the prostate-specific antigen （PSA） level declined ≥ 50%. DTX was restarted in patients with a PSA increase ≥ 25%. Sixty patients （group B） who had matching characteristics and had continuously received DTX without bicalutamide for 10-12 cycles were also enrolled. There were no statistically significant differences in progression-free survival （8 months vs. 9 months, P=0.866） or overall survival （19 months vs. 21 months, P=0.753） between groups A and B; however, the proportions of patients in group A with all grades of neutropenia （33% vs. 58%, P=0.013） and nausea/vomiting （11% vs. 29%, P=0.024） were significantly less compared to group B. A significant improvement in the global health and fatigue scores was recorded for group A post-chemotherapy compared to pre-chemotherapy （P〈0.05）. The fatigue, nausea/ vomiting and appetite loss scores in group B were increased post-chemotherapy compared to pre-chemotherapy （P〈0.05）. In conclusion, intermittent tri-weekly DTX plus bicalutamide is well tolerated and has the potential to achieve comparable disease control with an improvement in QoL for oatients with CRPC.

Urinary biomarkers for prostate cancer： a review

Although the routine use of serum prostate-specific antigen （PSA） testing has undoubtedly increased prostate cancer （PCa） detection, one of its main drawbacks is its lack of specificity. As a consequence, many men undergo unnecessary biopsies or treatments for indolent tumours. PCa-specific markers are needed for the early detection of the disease and the prediction of aggressiveness of a prostate tumour. Since PCa is a heterogeneous disease, a panel of tumour markers is fundamental for a more precise diagnosis. Several biomarkers are promising due to their specificity for the disease in tissue. However, tissue is unsuitable as a possible screening tool. Since urine can be easily obtained in a non-invasive manner, it is a promising substrate for biomarker testing. This article reviews the biomarkers for the non-invasive testing of PCa in urine.

Gemcitabine-based combination therapy compared with gemcitabine alone for advanced pancreatic cancer： a meta-analysis of nine randomized controlled trials

BACKGROUND： Pancreatic cancer is one of the most aggressive malignancies and chemotherapy is an effective strategy for advanced pancreatic cancer. Gemcitabine （GEM） is one of first-line agents. However, GEM-based combination therapy has shown promising efficacy in patients with advanced pancreatic cancer. This meta-analysis aimed to compare the efficacy and safety of GEM-based combination therapy versus GEM alone in the treatment of advanced pancreatic cancer.DATA SOURCES： A comprehensive search of literature was performed using PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. A quantitative meta-analysis was performed based on the inclusion criteria from all eligible randomized controlled trials. The outcome indicators included overall survival （OS）, 6-month survival, 1-year survival, progression-free survival/time-to-progression （PFS/TTP）, and toxicities. RESULTS： A total of nine randomized controlled trials involving 1661 patients were included in this meta-analysis. There was significant improvement in the GEM-based combination therapy with regard to the OS （HR=0.85, 95% CI： 0.76-0.95, P=0.003）, PFS （HR=0.76, 95% CI： 0.65-0.90, P-0.002）, 6-month survival （RR=1.09, 95% CI： 1.01-1.17, P=0.03）, and the overall toxicity （RR=l.68, 95% CI： 1.52-1.86, P〈0.01）. However, there was no significant difference in the 1-year survival.CONCLUSIONS： GEM-based combination chemotherapy might improve the OS, 6-month survival, and PFS in advanced pancreatic cancer. However, combined therapy also added toxicity.

Perioperative complications of radical retropubic prostatectomy in patients with locally advanced prostate cancer： a comparison with clinically localized prostate cancer

Radical prostatectomy （RP） continues to be an effective surgical therapy for prostate carcinoma, particularly for organ-confined prostate cancer （PCa）. Recently, RP has also been used in the treatment of locally advanced prostate cancer. However, little research has been performed to elucidate the perioperative complications associated with RP in patients with clinically localized or locally advanced PCa. We sought to analyse the incidence of complications in these two groups after radical retropubic prostatectomy （RRP）. From June 2002 to July 2010, we reviewed 379 PCa patients who underwent RRP in our hospital. Among these cases, 196 had clinically localized PCa （Tla-T2c group 1）, and 183 had locally advanced PCa （ ≥ T3,： group 2）. The overall complication incidence was 21.9%, which was lower than other studies have reported. Perioperative complications in patients with locally advanced PCa mirror those in patients with clinically localized PCa （26.2% vs. 17.8%, P=0.91）. Our results showed that perioperative complications could not be regarded as a factor to consider in regarding RP in patients with cT3 or greater.

Anti-angiogenesis in prostate cancer： knocked down but not out

Angiogenesis is a very complex physiological process, which involves multiple pathways that are dependent on the homeostatic balance between the growth factors （stimulators and inhibitors）. This tightly controlled process is stimulated by angiogenic factors, which are present within the tumor and surrounding tumor-associated stromal cells. The dependence of tumor propagation, invasion and metastasis on angiogenesis makes the inhibitors of new blood vessel formation attractive drugs for treating the malignancies. Angiogenesis can be disrupted by several distinct mechanisms： by inhibiting endothelial cells, by interrupting the signaling pathways or by inhibiting other activators of angiogenesis. This strategy has shown therapeutic benefit in several types of solid tumors, leading to Food and Drug Administration （FDA） approval of anti-angiogenic agents in the treatment of kidney, non-small cell lung, colon and brain cancers. Although no angiogenesis inhibitors have been approved for patients with metastatic prostate cancer, therapies that target new blood vessel formation are still an emerging and Dromising area of prostate cancer research.

Understanding the molecular pathogenesis and prognostics of bladder cancer： an overview

The knowledge of cellular mechanisms in malignances of the bladder has grown exponentially. Molecular technologies have led to the discovery of the molecular pathways distinguishing low-and high- grade urothelial neoplasms. This trend portends the future in which the classification and diagnosis of the bladder tumors through morphologic analysis will be supported by molecular information correlating with prognosis and targeted therapy. This article oudines tumor molecular pathology of bladder cancer with an emphasis on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer.

Androgen receptor expression in clinically localized prostate cancer： immunohistochemistry study and literature review

Aim： To evaluate androgen receptor （AR） expression in clinically localized prostate cancer （PCa）. Methods： Specimens were studied from 232 patients who underwent radical prostatectomy for clinically localized prostatic adenocarcinoma without neoadjuvant hormonal therapy or chemotherapy at our institution between November 2001 and June 2005. Immunohistochemical study was performed using an anti-human AR monoclonal antibody AR441. The mean AR density in the hot spots of different histological areas within the same sections were compared and the correlation of malignant epithelial AR density with clinicopathological parameters such as Gleason score, tumor, nodes and metastases （TNM） stage and pre-treatment prostate-specific antigen （PSA） value was assessed. Results： AR immunoreactivity was almost exclusively nuclear and was observed in tumor cells, non-neoplastic glandular epithelial cells and a proportion of peritumoral and interglandular stromal cells. Mean percentage of AR-positive epithelial cells was significantly higher in cancer tissues than that in normal prostate tissues （mean e SD, 90.0% ± 9.3% vs. 85.3% ±9.7%, P 〈 0.001）. The histological score yielded similar results. The percentage ofAR immunoreactive prostatic cancer nuclei and histological score were not correlated with existing parameters such as Gleason score, tumor, nodes and metastases stage and pre-treatment PSA value in this surgically treated cohort. Conclusion： The results of the present study suggest that there may be limited clinical use for determining AR expression （if evaluated in hot spots） in men with localized PCa.

TRP channels in prostate cancer： the good, the bad and the ugly？

During the last decade, transient receptor potential （TRP） channels emerge as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration. Initial studies showed that expression profile of some TRP channels, notably TRP melastatin 8 （TRPM8）, TRP vanilloid 6 （TRPV6）,TRP canonical （TRPC6） and TRPV2, is changing during the development and the progression of prostate cancer towards the hormone-refractory stages. The link between the change in expression levels and the functional role of these channels in prostate cancer is step by step being elucidated. These recent advances are here described and discussed.

Concurrent chemoradiotherapy for cervical cancer： background including evidence-based data, pitfalls of the data, limitation of treatment in certain groups

Concurrent chemoradiotherapy （CCRT） is regarded as the standard treatment for locally advanced uterine cervical cancer （LACC）, including stage Ib2-IVa disease [International Federation of Gynecology and Obstetrics （FIGO） staging]. However, approximately a third of eligible patients in previous studies died of LACC despite receiving CCRT. The therapeutic significance of CCRT alone in stage Ⅲ-IVa disease has not yet been confirmed. Effective treatment of some LACC is beyond the scope of CCRT. The objective of the present review is to highlight some challenging work aimed at overcoming this seemingly intractable disease. CCRT with increased peak concentrations of cisplatin （CDDP）, surgery following CCRT, adjuvant chemotherapy （CT） following CCRT, and neoadjuvant CT followed by CCRT are strategies expected to enhance the therapeutic efficacy of CCRT. If patients with LACC were divided into those with low-risk or high-risk systemic disease or prognoses, novel strategies should be assessed in the group with high-risk disease.

A potent chemotherapeutic strategy in prostate cancer： S-（methoxytrityl）-L-cysteine, a novel Eg5 inhibitor

Docetaxel-based combination chemotherapy remains the predominant treatment for castration-resistant prostate cancer. However, taxane-related drug resistance and neurotoxicity have prompted us to develop substitute treatment strategies. Eg5 （kinesin spindle protein）, which is crucial for bipolar spindle formation and duplicated chromosome separation during the early phase of mitosis, has emerged as an attractive target for cancer chemotherapy. The aim of this study was to investigate the anticancer efficacy of $-（methoxytrityl）-L-cysteine （S（MeO）TLC）, a novel Eg5 inhibitor in prostate cancer. Eg5 expression was examined in human prostate cancer cell lines and tissue microarrays were constructed from clinical specimens. Antiproliferative activity of S（MeO）TLC in prostate cancer cells was assessed by a cell viability assay. The anticancer effect and inhibitory mechanism of S（MeO）TLC in prostate cancer cells was further explored by Hoechst staining, flow cytometry and immunofluorescence. In addition, the antitumor effect of S（MeO）TLC on subcutaneous xenograft models was assessed. Eg5 expression was identified in PC3, DU145 and LNCaP cells. More than half of prostate cancer clinical specimens displayed Eg5 expression. S（Me0）TLC exhibited more powerful anticancer activity in prostate cancer cells compared with the other four Eg5 inhibitors tested. S（MeO）TLC induced cell death after arresting dividing cells at mitosis with distinct monopolar spindle formation. S（MeO）TLC exhibited its significant inhibitory activity （P〈0.05） on subcutaneous xenograft models also through induction of mitotic arrest. We conclude that Eg5 is a good target for prostate cancer chemotherapy, and S（MeO）TLC is a potent promising anticancer agent in prostate cancer.

Brain metastasis in advanced colorectal cancer： results from the South Australian metastatic colorectal cancer (SAmCRC) registry

Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Methods:The South Australian mCRC Registry(SAmCRC)was analyzed to assess the number of patients presenting with brain metastasis during their lifetime.Due to small numbers,a descriptive analysis is presented.Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis(1.4%).The clinical characteristics of those with brain metastasis were as follows:the median age was 65.3 years and 51% were female.Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation status of the tumor was known,the majority harbored a KRAS mutation(55%);31(53%)underwent craniotomy and 55(93%)underwent whole-brain radiotherapy.The median survival time from diagnosis of brain metastasis was 4.2 months(95% confidence interval 2.9–5.5).Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy(8.5 months vs.2.2 months,respectively).Data from the SAmCRC(a population-based registry)confirm that brain metastases are rare and the median time to development is approximately 2 years.Conclusions:Brain metastasis is a rare outcome in advanced CRC.Patients within the registry tended to be female,young in age,and harbored with higher rates of KRAS mutations.Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately,most patients with central nervous system involvement die from their extracranial disease.