Evaluation of conventional radiotherapy vs. conformal radiotherapy in the treatment of non-small-cell lung cancer after surgical resection

Objective： To compare the survival fractions and radiation-induced complications of conventional radiotherapy （CV） vs. conformal radiotherapy （CF） for non-small-cell lung cancer （NSCLC） after surgical resection. Methods： Between 1990 and 2002, 167 patients underwent post-radiotherapy either CV （n = 90） or CF （n = 77） for pathological IliA NSCLC at the University of Texas M.D. Anderson Cancer Center. Patients and tumor charactedstics were balanced in the two treatment groups. Surgical resection mainly consisted of Iobectomy and mediastinal lymph node dissection. In the CV group, postoperative radiotherapy was delivered to 54.3 Gy （range 22-69.6 Gy） in 27 fractions （range 11-58 f） for 5-6 weeks, while the CF group with RT to 53.9 Gy （range 50-63 Gy） in 26 fractions （range 25-33 f） for 5-6 weeks. Overall survival, disease-free survival, local control and distant metastasis-free survival were calculated using the Kaplan-Meier method. The complications of radiotherapy were also compared between the two groups. The median follow-up duration was 36 months in the CV group while 24 months in the CF group. Results： No statistically significant differences were found in terms of disease-free survival, local-regional control and distant metastasis-free survival in the two treatment groups. However, the overall survival was found statistically significant different in the two groups （P = 0.014）. Postoperative radiotherapy complications such as weight loss, skin reaction, dysphagia, and cardiac related complication were similar in the two groups although the lung fibrosis, cardiac complications and hematologic complications were significantly different, and 8 cases of death in the CV group associated with cardiac complications while none was observed in the CF group. Conclusion： The treatment of stage IliA NSCLC using either CV or CF postoperative radiotherapy resulted in similar outcomes in terms of local control, disease-free survival and most of complications. However, CF could achieve better overall survival and less complications such as lung fibrosis, cardiac complications and hematologic complications. The advantage is worth further observation.

Mouse models of Mdm2 and Mdm4 and their clinical implications

Mdm2 and Mdm4 are two key negative regulators of the tumor suppressor p53.Deletion of either Mdm2 or Mdm4 induces p53-dependent early embryonic lethality in knockout mouse models.The tissuespecific deletion of Mdm2 induces p53-dependent apoptosis,whereas the deletion of Mdm4 induces both p53-dependent apoptosis and cell cycle arrest.Compared to Mdm4 deletion,Mdm2 deletion causes more severe phenotypic defects.Disrupting the Mdm2 and Mdm4 interaction using knockin mice models causes embryonic lethality that can be completely rescued by the concomitant loss of p53,suggesting that Mdm2 and Mdm4 heterodimerization is critical to inhibit p53 activity during embryogenesis.Overexpression of Mdm2 and Mdm4 in mice induces spontaneous tumorigenesis,which clearly indicates that Mdm2 and Mdm4 are bona fide oncogenes.Studies from these mouse models strongly suggest that blocking Mdm2and Mdm4-mediated p53 inhibition is an appealing therapeutic strategy for cancer patients with wild-type p53 alleles.

Decoding the dual-coding the translational potential transcript region： key factors influencing of a two-ORF-containing

A dual-coding region is defined as a stretch of DNA that encodes amino acids in overlapping reading frames. Dual-coding regions are often found in bacteriophages and viruses （e.g., HIV） with tiny genome sizes; such an arrangement is believed to greatly increase genetic information storage efficiency [1]. In mammals, genetic information storage is not an issue because the mam- malian genorne is huge and contains large amounts of non-coding sequences. Coding regions usually encode amino acids only in one reading frame,

Molecular epidemiology of DNA repair gene polymorphisms and head and neck cancer

Although tobacco and alcohol consumption are two common risk factors of head and neck cancer （HNC）, other specific etiologic causes, such as viral infection and genetic susceptibility factors, remain to be understood. Hu- man DNA is often damaged by numerous endogenous and exogenous mutagens or carcinogens, and genetic vari- ants in interaction with environmental exposure to these agents may explain interindividual differences in HNC risk. Single nucleotide polymorphisms （SNPs） in genes involved in the DNA damage-repair response are reported to be risk factors for various cancer types, including HNC. Here, we reviewed epidemiological studies that have assessed the associations between HNC risk and SNPs in DNA repair genes involved in base-excision repair, nucleotide-excision repair, mismatch repair, double-strand break repair and direct reversion repair pathways. We found, however, that only a few SNPs in DNA repair genes were found to be associated with significantly in- creased or decreased risk of HNC, and, in most cases, the effects were moderate, depending upon locus-locus in- teractions among the risk SNPs in the pathways. We believe that, in the presence of exposure, additional pathway- based analyses of DNA repair genes derived from genome-wide association studies （GWASs） in HNC are needed.

The diagnosis and differential diagnosis of granulocytic sarcoma

Objective： To discuss the diagnosis and differential diagnosis of granulocytic sarcoma （GS）. Methods： Six cases were reported in this paper. They were assessed by pathologists. Immunohistochemistry （IHC） stain and routine hematoxylin and eosin （H＆E） stain were applied. Results： All patients involved in different anatomic sites respectively including skin, lymph node, soft tissue, breast, cervix and penis. All cases were previously error diagnoses. Three of them were initially diagnosed as non-Hodgkin lymphoma （NHL）. One case of cervical lymph node lesion was first considered as metastasized carcinoma by clinician. One biopsied skin sample was initially reported as Karposi＇s sarcoma. And one breast case was suspicious of the Iobular carcinoma with the frozen samples without antecedent clinical history information. GS was accompanied with acute myeloid leukemia （AML） in one case and with acute lymphocytic leukemia （ALL） in one case. Histopathologically, blastic, immature and differentiated variants were found in four, one and one, respectively. Immunohistochemistry （IHC） showed that myeloperoxidase （MPO） and lysozyme were both found to be positive in all cases, CD43 was found in 5 of 6 cases. Three of six cases were CD68, CD15 and LCA positive. CD34 and CDl17 were positive in 1/5 and 1/6 cases, respectively. However, CD20 and CD3 were negative in all cases. Conclusion： GS was uncommon and it may be misdiagnosed easily in routine practice. Each area had its own character, but they had the common features too. It can be correctly diagnosed by combination of H＆E stain, IHC stain, peripheral blood and bone marrow. MPO and Lysozyme were necessary for the nature of granulocytes. In addition, CD43, CD68 and CD15 were very helpful.

Role of human papillomavirus and cell cycle-related variants in squamous cell carcinoma of the oropharynx

SCCOP is a subset of squamous cell carcinoma of the head and neck and is characterized by aggressive local tumor growth that requires morbid local-regional therapies. It has a moderately high recurrence rate, common medical comorbidities, and a high frequency of second primary tumorst^a. It is estimated that in the USA approximately 9,000 new cases of SCCOP were diagnosed and 2,110 deaths would result from these cancers in 2006. The median age at diagnosis is approximately 60 y, and this disease occurs more frequently in men （-75%） than in womenta.

Detection of RASSF1A promoter hypermethylation in serum from gastric and colorectal adenocarcinoma patients

AIM：To evaluate the diagnostic role of serum RASSF1A promoter hypermethylation in gastric and colorectal adenocarcinoma. METHODS：Methylation-specific polymerase chain reaction （MSPCR） was used to examine the promoter methylation status of the serum RASSF1A gene in 47 gastric adenocarcinoma patients, 45 colorectal adenocarcinoma patients, 60 patients with benign gastrointestinal disease （30 with benign gastric disease and 30 with benign colorectal disease）, and 30 healthy donor controls. Apaired study of RASSF1A promoter methylation status in primary tumor, adjacent normal tissue, and postopertive serum were conducted in 25 gastric and colorectal adenocarcinoma patients who later were underwent surgical therapy. RESULTS：The frequencies of detection of serum RASSF1A promoter hypermethylation in gastric （34.0%） and colorectal （28.9%） adenocarcinoma patients were significantly higher than those in patients with benign gastric （3.3%） or colorectal （6.7%） disease or in healthy donors （0%） （P 〈 0.01）. The methylation status of RASSF1A promoter in serum samples was consistent with that in paired primary tumors, and the MSPCR results for RASSF1A promoter methylation status in paired preoperative samples were consistent with those in postoperative serum samples. The serum RASSF1A promoter hypermethylation did not correlate with patient sex, age, tumor differentiation grade, surgical therapy, or serum carcinoembryonic antigen level. Although the serum RASSF1A promoter hypermethylation frequency tended to be higher in patients with distant metastases, there was no correlation between methylation status and metastasis. CONCLUSION：Aberrant CpG island methylation within the promoter region of RASSF1A is a promising biomarker for gastric and colorectal cancer.

Bone marrow niche-mediated survival of leukemia stem cells in acute myeloid leukemia: Yin and Yang

Acute myeloid leukemia （AML） is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow （BM） niche is critical to the maintenance and retention of hematopoietic stem cells （HSC）, including leukemia stem cells （LSC）, and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.

MicroRNA therapeutics:principles,expectations,and challenges

MicroRNAs(miRNAs) are a class of highly abundant non-coding RNA molecules that are involved in several biological processes.Many miRNAs are often deregulated in several diseases including cancer.There is substantial interest in exploiting miRNAs for therapeutic applications.In this editorial,we briefly review current advances in the use of miRNAs or antisense oligonucleotides(antagomirs) for such therapies.One of the key issues related to therapy using miRNAs is degradation of naked particles in vivo.To overcome this limitation,delivery systems for miRNA-based therapeutic agents have been developed,which hold tremendous potential for improving therapeutic outcome of cancer patients.

Mouse models for cancer research

Mouse models of cancer enable researchers to learn about tumor biology in complicated and dynamic physiological systems. Since the development of gene targeting in mice, cancer biologists have been among the most frequent users of transgenic mouse models, which have dramatically increased knowledge about how cancers form and grow. The Chinese Journal of Cancer will publish a series of papers reporting the use of mouse models in studying genetic events in cancer cases. This editorial is an overview of the development and applications of mouse models of cancer and directs the reader to upcoming papers describing the use of these models to be published in coming issues, beginning with three articles in the current issue.

MYC-microRNA-9-metastasis connection in breast cancer

Metastasis accounts for more than 90% of cancer patients＇ mortality. The metastatic process involves multiple steps [1]. Initially, cancer cells from the primary tumor invade adjacent stroma. To acquire this capacity, cells undergo a process called epithelial-mesenchymal transition （EMT）, in which cells in response to signals from the surrounding stroma, undergo a switch between cell phenotypes and acquire mesenchymal properties and show reduced intercellular adhesion, allowing cells to become motile.

Challenge of hepatitis C in Egypt and hepatitis B in Mauritania

Egypt has one of the highest prevalence rates of hepatitis C virus(HCV) in the world,mostly with genotype 4 that is highly associated with severe fibrosis. As a consequence,hepatocellular carcinoma has become the leading cause of cancer in this country. Mauritania is a highly endemic area for hepatitis B virus(HBV). HBV and HCV could both be iatrogenically transmitted through infected blood products,infected needles,and medical equipment improperly sterilized. Adequate and efficient healthcare and public health measures with good surveillance programs,access for screening,prevention strategies,and successful treatment are needed to halt the spread of these diseases. Herein,we have reviewed the epidemiology,modes of transmission,predisposing factors,and novel treatment modalities of these viruses. We have proposed practices and interventions to decrease the risk of transmission of HCV and HBV in the affected countries,including strict adherence to standard precautions in the healthcare setting,rigorous education and training of patients and healthcare providers,universal screening of blood donors,use of safetyengineered devices,proper sterilization of medical equipment,hepatitis B vaccination,as well as effective direct-acting antiviral agents for the treatment of HCV.

Fatty Acid Binding Protein-4 Silencing Attenuates Atherosclerosis Progression by Affecting Macrophage Apoptosis and Autophagy

Background: Atherosclerosis, which is the principal cause of heart attacks and strokes, is the leading cause of death in the United States. Various biological processes such as apoptosis and autophagy are involved in almost every stage of atherosclerosis, which could lead to plaque instability causing stroke and death. Fatty Acid Binding Protein 4 (FABP4) is an adipokine released by macrophages and is involved in multiple disease conditions including stroke. However, the association of FABP4 with macrophage apoptosis and autophagy in atherosclerosis has not been elucidated. We hypothesize that silencing FABP4 protein could be a novel therapeutic approach to attenuate macrophage apoptosis and autophagy thereby minimizing plaque instability in atherosclerosis. Methods: RAW264 mouse macrophage cells were transfected with siRNA control liposome quantum dots (QD), siFABP4 liposome QD at the concentration of 150 μg/ml total lipids, or TNF-α at 100 ng/ml. Western blot and reverse phase protein array (RPPA) analysis were completed. Results: Inhibiting the translation of FABP4 blocked the apoptotic pathway as evidenced from the increased expression of anti-apoptotic BCL-xL and BCL-2 along with reduced expression of BAX and activated Caspase 3 levels. Beclin-1 and LC3-II levels were also reduced with knocking down FABP4 indicating the attenuation of autophagy. Conclusion: Targeting FABP4 protects against macrophage processes associated with the progression of atherosclerosis.

Morphological and molecular basis of ovarian serous carcinoma

Serous carcinoma is the most common type of epithelial ovarian cancer. In this review, we provide a com- prehensive picture of ovarian serous cancers from multiple aspects： the first part of this review summarizes the morphological, histological, and immunological signatures of ovarian serous carcinoma; subsequently, we review the history of the evolvement of different grading systems used in ovarian serous cancer; in the end, we focus on characterizing the genetics that underlie the 2-tiered pathways through which ovarian serous cancers are believed to arise： the low-grade and the high-grade pathways.

Prevention of H2O2 Induced Oxidative Damages of Rat Testis by Thymus algeriensis

Objective We evaluate the effects of Thymus algeriensis （TEO） against hydrogen peroxide （H202） toxicity on body and testis weight, testis sperm count, testis lipid peroxidation, and antioxidant enzyme activities in rats. Methods Rats were treated with low （LD） and high dose （HD） of H202 （0.1 and 1 mmol/L） in the presence or absence of TEO （150 mg/kg）. Results The results exhibited a significant decrease in body weight and testis weight, in total sperm number decrease （P〈0.05）, sperm motility and percentage of sperm viability, leading to complete arrest, in sperm flagellar beat frequency by the gavage of 1 mmol/L H202 compared to controls. The administration of H2O2 resulted in a significant reduction in testis GSH, GPx, CAT, SOD, and GST activity and significant increase （P〈0.05） in MDA concentration compared with the untreated control animals. TEO pre-treatment protected testis from the H2O2 generated oxidative stress. These results were confirmed by histological architecture examinations. Conclusion H2O2 has the ability to alter the sperm function, characteristics and development of testis. However, TEO is an efficient natural agent, which can prevent the testis from H2O2-induced oxidative damage in rats.

Patient-Specific and Generic Immobilization Devices for Prostate Radiotherapy

The purpose of our study was to compare interfractional bony setup variations in pelvic anatomy with two immobilization devices, the patient-specific Vac-Lok and the generic Dual Leg Positioner system (both Civco Medical Solutions, Kalona, IA), for bilateral proton radiotherapy of the prostate. Two groups of 10 patients were studied. Computed tomography (CT) was performed three times a week, yielding 233 CT image sets for the vacuum system group and 252 for the other group. The translational shifts of the pelvic bone and prostate and rotation of the upper femurs of the femoral heads with respect to the simulation CT images were analyzed. Along the anterior-posterior and lateral axes, mean and systematic translational variations of the pelvic bone and prostate, relative to skin fiducials, were significantly lower in the Vac-Lok group (all p 0.01) than in the Dual Leg Positioner group. Abduction of the upper femur, the dominant rotation, had random rotational variations of 1.9° and 2.0° and systematic rotations of 3.1&#176 and 2.9&#176 for the vacuum and generic system groups, respectively. Femoral abduction was highly correlated with anterior prostate displacement for both femurs in both groups (p tion introduced during simulation CT, particularly with the generic immobilization system. High degrees of femoral rotation may introduce prostate translation and distal misalignment of lateral proton beams with the prostate.

Principal Component Analysis of EBT2 Radiochromic Film for Multichannel Film Dosimetry

Radiochromic film with a dye incorporated into the radiation sensitive layer [Gafchromic EBT2, Ashland, Inc.] may be digitized by a color transparency scanner, digitally processed, and calibrated so that a digital image in units of radiation absorbed dose is obtained. A transformation from raw scanner values to dose values was developed based upon a principal component analysis of the optical densities of the red, green and blue channels of the color image of a dose of 0.942 Gy delivered by a Sr-90/Y-90 disk-shaped source. In the order of increasing eigenvalue, the three eigenimages of the principal component analysis contained, by visual inspection, 1) mainly noise;2) mainly a pattern of irregular streaks;and 3) most of the expected dose information along with some of the same background streaking that predominated in the second eigenimage. The combination of the second and third eigenimages that minimized the background streaking was converted into a transformation of the red, green and blue channels’ optical densities and applied to films with a range of doses from 0 to 63.7 Gy. The curve of dose vs. processed optical density was fit by a two-phase association curve. This processing was applied to a film exposed from its edge by a different Y-90 source in a configuration that was modeled by Monte Carlo simulation. The depth-dose curves of the measurement and simulation agree closely, suggesting that this approach is a valid method of processing EBT2 radiochromic film into maps of radiation absorbed dose.