Dr. Lei Hou obtained his B.S. Degree at Chengde Medical College in China in 1999, and completed his M.S. and M.D. at Beijing Institute of Heart, Lung and Blood Vessel Diseases in 2003 and Peking Union Medical College in 2014, respectively. He joined National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention as an associate research fellow in July 2014. Until now, he has published 40+ papers including 6 SCI articles with average impact factor of published papers (first author) over 5. His current research is focused on disease surveillance, control of tobacco and hypertension, and public health policy.
Abstract: Extra-hepatic cholangiocarcinoma (ECC) has become one of the most rapidly increasing malignancies in China in the past decades. Relationship between tobacco exposure and ECC epidemic is unclear; this study is aimed to explore this relationship.
We included 55,818 participants aged 30 years or older in the National Mortality and Smoking Survey of China. Smoking for participants and spouses was defined as 1 cigarette or more per day for up to 1 year. Spouses’ smoking was taken as a measure of exposure to passive smoking. Smoking information in 1980 was ascertained and outcomes were defined as ECC mortality in 1986–1988. We found that smoking, either passive or active, increased risk of death from ECCs by 20% (risk ratio [RR], 1.20; 95% confidence interval [CI], 0.99–1.47), compared with no exposure to any tobacco. This risk was a notable 98% (RR, 1.98; 95% CI, 1.49–2.64) for individuals exposed to passive plus active smoking. These findings were highly consistent among men and women. Pathology-based analyses show dose-response relationships of ECC with pack-years from all types of smoking exposure (Ps for trend < 0.05); the RR was up to 2.75 (95% CI, 1.20–6.30) in individuals exposed to combined smoking with the top exposure dose. Non-pathology-based findings were similar.
This study indicates that tobacco exposure increases ECC risk. Given a dramatic increase of exposure to second-hand smoke and cases with ECC, an inadequate provision of smoke-free environments could contribute to ECC epidemic and further challenge public health and medical services based on current disease spectrum.
Abstract: Cervical cancer, one of the few cancers that can be prevented, is the first most common cancer of women in sub-Saharan Africa, especially in Burkina Faso, where it is also the leading cause of cancer related deaths. The high-risk human papillomavirus (HR-HPV) is responsible for this cancer and is also implicated in others such as Otorhinolaryngological cancers.
Objective: to determine high-risk HPV genotypes involved in cervical cancer and in Otorhinolaryngological cancers histologically confirmed in Burkina Faso.
Methods: 14 high-risk oncogenic HPV genotypes were investigated by multiplexed real-time PCR from archived fixed and paraffin-embedded tissues of the histological diagnosed invasive cervical cancer and Otorhinolaryngological cancers. These samples of cancerous tissue came from Burkina, Benin and Mali.
Results: Squamous cell carcinoma (SCC) was more common than adenocarcinoma (ADC). All 14 genotypes were identified in invasive cancer of the cervix. In contrast, 7 of the 14 genotypes were found in cancer cases of the Otorhinolaryngological cancers. Genotypes more common in invasive cervical cancer, were in descending order, respectively; in Benin: HPV 39, HPV 18, HPV 45, HPV 35, HPV 52 and HPV 31; in Burkina Faso: HPV 18, HPV 39, HPV 45, HPV 31, HPV 16, HPV 35; then in Mali: HPV 18, HPV 31, HPV 33, HPV 45, HPV 16, HPV 56, HPV 58 and HPV 52. In cancers of the Otorhinolaryngological, seven high-risk HPV genotypes were identified; whose predominant genotypes were HPV56, HPV 33, followed by HPV 52, HPV 45, HPV 39, HPV 18 and HPV16.
Conclusion: This study notes in histologically confirmed invasive cervical cancers and Otorhinolaryngological cancers, a diversity of the distribution of high-risk HPV genotypes involved. The prevention-based fight against cervical cancer with sensitization, screening and prophylactic anti-HPV broad-spectrum vaccination needs to be strengthened
Abstract: Background: The global burden of hematologic malignancy (HM) is rapidly rising with aging, exposure to polluted environments, and global and local climate variability all being well-established conditions of oxidative stress. However, there is currently no information on the extent and predictors of HM at Kinshasa University Clinics (KUC), DR Congo (DRC).
This study evaluated the impact of bio-clinical factors, exposure to polluted environments, and interactions between global climate changes (EL Nino and La Nina) and local climate (dry and rainy seasons) on the incidence of HM.
Methods: This hospital-based prospective cohort study was conducted at Kinshasa University Clinics in DR Congo. A total of 105 black African adult patients with anaemia between 2009 and 2016 were included. HM was confirmed by morphological typing according to the French-American-British (FAB) Classification System. Gender, age, exposure to traffic pollution and garages/stations, global climate variability (El Nino and La Nina), and local climate (dry and rainy seasons) were potential independent variables to predict incident HM using Cox regression analysis and Kaplan Meier curves.
Results: Out of the total 105 patients, 63 experienced incident HM, with an incidence rate of 60%. After adjusting for gender, HIV/AIDS, and other bio-clinical factors, the most significant independent predictors of HM were age ≥ 55 years (HR = 2.4; 95% CI 1.4–4.3; P = 0.003), exposure to pollution and garages or stations (HR = 4.9; 95% CI 2–12.1; P < 0.001), combined local dry season + La Nina (HR = 4.6; 95%CI 1.8–11.8; P < 0.001), and combined local dry season + El Nino (HR = 4; 95% CI 1.6–9.7; P = 0.004). HM types included acute myeloid leukaemia (28.6% n = 18), multiple myeloma
(22.2% n = 14), myelodysplastic syndromes (15.9% n = 10), chronic myeloid leukaemia (15.9% n = 10), chronic lymphoid leukaemia (9.5% n = 6), and acute lymphoid leukaemia (7.9% n = 5). After adjusting for confounders using Cox regression analysis, age ≥ 55 years, exposure to pollution, combined local dry season + La Nina and combined local dry season + El Nino were the most significant predictors of incident hematologic malignancy.
Conclusion: These findings highlight the importance of aging, pollution, the dry season, El Nino and La Nina as related to global warming as determinants of hematologic malignancies among African patients from Kinshasa, DR Congo. Cancer registries in DRC and other African countries will provide more robust database for future researches on haematological malignancies in the region.
Abstract: Small Cell Lung Cancer accounts for about 15% of the total number of lung cancer which is highest incidence of brain metastases in all type of lung cancer.Once brain metastases occurs, the median survival time of patients will be significantly shortened. If not treated, the median survival time is only 1-2 months. Even for patients who are effective in fist-line chemotherapy, the probability of brain metastases will still be as high as 80% in 2 years .Brain metastasis is also an important cause of recurrence, metastases and death of small cell lung cancer. Therefore, it is important to early detect high-risk group of brain metastases and prevent the brain metastases. A retrospective study was to decompose the risk factors of brain metastases and construce a prediction model of brain metastases in small cell lung cancer.At the same time, PCI prolongs the patient's progression free survival time (PFS)（P=0.002）.
118 cases of Small Cell Lung Cancer of the first affiliated hospital of Guangzhou Medical University were analyzed retrospectively. We collected and analyzed the preliminary diagnosis clinical data, including gender, age, physical status, primary tumor location, staging, tumor markers,anemia, hyponatremia , distant metastasis and collected prophylactic craniocerebral irradiation (PCI) treatment. Single factor COX regression analysis and multiple factor COX regression analysis were used to study the clinical risk factors involved and analyses the effect of PCI on the risk of brain metastases in small cell lung cancer. Using these clinical parameters and the coefficients obtained in multifactor analysis, we will establish a risk prediction model for the brain metastases of small cell lung cancer.
A total of 44 patients had brain metastases during the follow-up period, accounting for 37.3% of the study population. The statistical results of single factor showed that smoking index>400, extensive stage, PS >= 2, NSE higher than the normal range, LDH higher than the normal range, hyponatremia, lymph node metastasis were the risk factors for brain metastasis in small cell lung cancer patients , multiple factor analysis showed that smoking index> 400 (P<0.001), PS >=2 (P<0.001) and NSE higher than the normal range (P=0.002) can significantly increase the risk of small cell lung cancer with brain metastasis. Based on the analysis result of the above factors, the smoking index >400, PS >= 2, NSE higher than the normal range, a small cell lung cancer with brain metastasis prediction model and risk points, to distinguish among low risk,middle and high-risk groups.The prediction model has the remarkable significance (P<0.001). PCI can reduce the incidence of brain metastases in small cell lung cancer and delay the time of brain metastasis (P=0.029). PCI prolong
The smoking index > 400, PS>=2, NSE higher than the normal value rangeand increased the risk of small cell lung cancer with brain metastasis, the brain metastases prediction model of small cell lung cancer according to these three factors has remarkable significant , and we find that prophylactic cranial irradiation can decrease the incidence of brain metastases and significantly delay the occurrence of the brain metastases. In the future medical practice, patients with high risk brain metastasis should be followed up closely for early diagnosis and treatment. Preventive treatment of brain metastases, such as prophylactic cranial irradiation, should be advocated in clinical practice.
Abstract: The mainstay of treatment for curable endometrial cancer (EC) involves surgery with adjuvant radiotherapy in general and brachytherapy in particular as an important adjunct treatment. Histology of EC is a major determining factor for intracavitary brachytherapy (ICRT) treatment volume in early stage EC. Many guidelines such as the American Brachytherapy Society recommend treatment of an extended volume up to the whole length of the vaginal stump (VS) for cases of high risk histologies (HRH). Since both the proximal and distal vagina is recommended for ICRT and the risk of disease recurrence is higher in proximal vagina , a differential dosing of proximal and distal VS has the potential to achieve targeted therapeutic doses to at risk areas without further compromise to critical structures. We present a simulated novel way to treat the VS by ICRT in cases of EC with HRH. Analysis of the simulated and approved plans allow us to compare the doses to organs at risk (OAR’s).
Material and methods: Seventy-five cases from July 2017-August 2018 were reviewed and twenty-five (25) met the criteria for inclusion in this study. All these cases received External Beam Radiation Therapy (EBRT) dose of 50.4Gy/28. The ICRT simulation Computed Tomography (CT) dataset was subsequently used to generate the study plan which was then compared to the actual treatment plan.
Study plan In order to treat the whole VS but spare OARs a club-shaped design was proposed. This technique involved treating the upper 1/3 with a prescription point at 0.5cm lateral to the applicator surface and the lower 2/3 with a prescription point at the applicator surface. The length of the VS was defined from the tip of the applicator to 2cm superior to the introitus.
The treated length was recorded and ranged from 8-10cm for each case. The D2cc values for the contoured bladder and rectum were extracted from the treatment plan and used along with the D2cc values from the EBRT treatment to calculate OAR EQD2. QUANTEC Constraints used were (ICRU 83): EQD2 bladder: 90Gy; EQD2 rectum: 75Gy. Once calculated, the results were analyzed and the percent deviation between the proposed plan and the constraints as well as the approved plan were determined. The mean and standard deviations were then determined and recorded for each comparison.
Results: Upon review of histologies, twelve (12) of twenty-five (25) cases were HRH cases (Incidence 1 in 2).
The club-shaped design to treat the whole VS did not cause further compromise to the bladder (EQD2: 22% below constraints) or the rectum (EQD2: 1% below constraints). There was only a 2% difference between the final constraints in both treatment techniques.
Conclusion: This novel technique to treat the full VS length can be used without adversely affecting OARs toxicities with the potential to offer superior coverage to at risk areas while maintaining dose constraints to organs at risk. The strength of these results, however, is limited by the small sample size and a larger well designed trial is definitely warranted.
Biography: Dr Fu has completed his MD and PhD from Wuhan University and Chinese University of Hong Kong and postdoctoral studies from Vanderbilt University School of Medicine. He worked as a Tennure –Track faculty of NCI, USA before he came back to China. He is now the vice director of Cancer Center, Remin Hospital of Wuhan University. He has extensive expereiences in Radiation Oncology and Cancer Translational Research. He has published more than 30 papers in reputed journals and has been serving as board members for many national as well as international expect commeetees.
Abstract: Treatment for patients with stage IV small (SCLC) or non-small cell lung cancer (NSCLC) has been mainly systematic therapy. At present, an array of molecular targeted therapy and immunotherapy has been used for the treatment of metastatic lung cancer. With the prolongation of survival of metastatic lung cancer patients, the importance of local control for the primary and metastatic lesions like radiotherapy is emerging. Palliative radiotherapy used to control the primary as well as metastatic tumors could reduce intra-thoracic disease burden, bronchial/vascular compression and pulmonary symptoms. Aggressive radiotherapy can play a positive role if applied properly. For AD with brain metastasis, radiotherapy can significantly improve patients’ survival. In addition, studies have shown that stereotactic ablative radiotherapy (SABR) is an applicable treatment for oligo-metastic lung cancer. Our previous SEER study also showed radiation therapy in addition to chemotherapy might be beneficial for the survival of patients with metastatic NSCLC, even for patients with extensive metastases. Compared with NSCLC, radiotherapy has a more pronounced effect on SCLC. As systemic therapies such as immunotherapies improve, the approach of consolidative local therapy will likely become more relevant. Multifocal radiation therapy combined with immunotherapy has been explored to provide better therapeutic results than either alone. With the advancement of systematic therapy, it might also be possible for surgery to manage the residue disease after systematic treatment and radiotherapy. Surgery may work with new strategies such as SABR to multiple metastatic sites with immunotherapy to cure more metastatic lung cancer. However, sufficient nutrition support will be extremely important to ensure patients can tolerant these intensive multidisciplinary treatments. To significantly reduce the normal tissue complication probability, more advanced radiotherapy techniques such as SABR by means of proton or heavy-ion radiotherapy should be explored.
Biography: Dr Tomasz Powrózek is a research associate at Department of Human Physiology; Medical University of Lublin, Poland. During his doctoral training, he developed new potential markers for early lung cancer detection based on analysis of epigenetics markers using liquid biopsy. Nowadays, he is active in investigation of novel molecular markers in blood circulation of head and neck cancer patients (detection, prediction and prognosis). The main area of interest concerns understanding the molecular background of malnutrition and cachexia in cancer patients. Dr Powrózek is an author of over 110 scientific reports as well as he reviewed over 180 papers.
Abstract: Background: Unfavorable changes in body composition are frequent event among head and neck cancer (HNC) patients undergoing (RTH). Nutritional deficits developing as an effect of applied therapy negatively affect to patients’ quality of life, survival and therapy outcomes and can contribute to either malnutrition and cachexia. Investigation of novel predictive markers could select group of patients being at a risk of body composition changes and hence allow introduce them to early nutritional intervention and supportive care to prevent malnutrition. In present study we demonstrated novel approach to prediction of RTH-induced changes in body composition using phase angle (PA) derived from bioelectrical impedance analysis (BIA) in combination with molecular marker, the miRNA-181a expression.
Results: Patients with simultaneous presence of low PA and high miRNA-181a had significantly worse body composition characteristics after the commencement of RTH and were more susceptible to unfavorable changes of fat-mass, body weight and BMI in contrast to other patients . Individuals with unfavorable pattern of both factors were at a significantly higher risk of decreasing the FM <16kg (OR=6.0; p=0.038) and FFM <44.7kg (OR=5.50; p=0.044) during the therapy period. ROC analysis allowed to predict changes in fat-free mass index, lean mass, BMI and total protein with AUC over 0.700.
Conclusion: Simultaneous evaluation of two independent markers can demonstrate higher diagnostic accuracy and predictive value for detecting RTH-induced changes in body composition of cancer patients.
Abstract: Background: There are about 15-20% colorectal cancer developed from colitis. The most common forms of inflammatory bowel disease are Crohn’s disease (CD) and ulcerative colitis (UC).The pathogenesis of UC and CD is various and including immunologic, environmental and genetic factors.Excessive reactive oxygen species (ROS) production has been observed in the inflamed mucosa of IBD patients. ROS is widely known as a negative factor on cancer initiation,progression and survival stage. NADPH oxidases (NOXs) are the main resource of ROS. Although diphenyleneiodonium (DPI) were assessed as inhibitors of both mitochondrial respiration and ROS synthesis and used in research for decades, few research using it as an potential drug in mice model.
Methods: We used male C57BL/6 mice were treated with 3.5% DSS and 2% DSS respectively for five days and seven days to make fatal enteritis and early stage colitis. After the DSS period, ultra-low dose DPI or control solvent was intraperitoneal injection everyday. Then, the survival rate and inflammatory level of intestinal tract in different groups were observed. Quantitative PCR and enzyme-linked immuno sorbent assay (ELISA) were applied to evaluate the inflammatory factors between experimental and control groups. Intracellular ROS were meatured by fuorescence microscopy using 2’7’-dichlorofluorescein diacetate(DCFH-DA). Htoxylin-eosin (H&E) staining assessed histological patterns of several organs in DPI group and control group. Disease activity index and histological activity index were assessed. Certain signal pathways were verified on protein level.
Results: In the fatal enteritis model, compared with control group, ultra-low dose DPI group has a better survival rate. In early stage colitis model, mice’s weight and colon length are better than those in control group. The level of inflammatory factors--COX2, IL6 ,TNF-a and IL12 are lower than the control group. In RAW246.7 cell line, compared with other concentrations, ultra-low dose DPI group had a lower level of inflammatory factor, such as COX2, IL6, CCL5, IP10, TNF-a and MCP1.Utral-low dose DPI could inhibited NF-κB and MAPK pathway. Histological patterns of DPI and control groups had no significant differences.
Conclusion: Ultra-low dose DPI could prevent the progress of inflammatory bowl diseases and have no negative effect on other organs.This study will provide a new pharmacological evidence that ultra-low dose DPI has a positive significance for prevention of colitis-associated colorectal cancer.
Biography: Ahmed Eleojo Musa has an MSc in Medical Physics at Tehran University of Medical Sciences, International Campus, Tehran, Iran. He specializes in radiation therapy, radiation biology, nuclear medicine and medical imaging. Presently, he is a research assistant at the Research Centre for Molecular and Cellular Imaging, Imam Hospital, Tehran, Iran. He has published a number of papers in reputable international journals with more still under peer review
Abstract: Majority of cancer treatment is done with radiotherapy . The ultimate goal of radiotherapy is the delivery of a dose of radiation to kill or subdue cancer cells with minimal side effects to normal tissues. Radiation effects on tissues produce free radicals that cause biological damages. The skeletal muscle is the largest organ in the body, hence it could be affected by the detrimental effects of ionizing radiation. To reverse these effects, we used melatonin, a neurohormone secreted by the pineal gland in mammals, as a radioprotector, due to its abilities to function as a free radical scavenger, anti-inflammatory and potent anti-oxidant effects [2, 3].
Twenty male Wistar rats were randomly assigned to 4 groups: control (C), melatonin (M), radiation (R) and melatonin + radiation (MR). 100 mg/kg of melatonin was administered to the rats 30 minutes before irradiation of their right femoral muscles with a single dose of 20 Gy  gamma radiation, while the rest part of their bodies were shielded. All rats were sacrificed for biochemical evaluation after 2 days.
Our results showed radiation-induced biochemical changes in normal rats’ femoral muscle tissues. Biochemical analysis showed that malondialdehyde (MDA) levels significantly increased in R group (P<0.001) and decreased significantly in M and MR groups after 2 days (P<0.005). Catalase (CAT) and superoxide dismutase (SOD) activities decreased in the R group (P<0.001) while it increased in M and MR groups during the same time period compared with the C group (P<0.005). However, treatment with melatonin reversed these effects (P<0.005).
Based on the results obtained, we can conclude that melatonin can improve biochemical changes of irradiated muscle tissues. We recommend its use in optimal and safe dose for effective protection of muscle tissues, and increased therapeutic ratio of radiotherapy.
Biography: Stuart is a final year PhD student working within the Strathclyde Institute of Pharmacy & Biomedical Science (SIPBS) at the University of Strathclyde, having graduated previously from Strathclyde with a B.Sc. Honours degree in Biochemistry and Pharmacology. Stuart’s research focusses on the role of inhibitory kappB kinases (IKKs) in cancer, in particular considering novel regulatory signalling roles for IKKs out-with the recognised IKK-NF-κB pathways. This includes a focus on IKK-Aurora kinase A (AURKA) protein-protein interactions (PPIs), associated signalling cross-talk and whether these interactions may potentially be targetable in prostate cancer via development of peptide based disruptors of IKK-Aurora kinase PPIs.
Abstract: Aurora kinase A (AURKA) is a member of a family of conserved serine/threonine mitotic kinases that is overexpressed in cancer and when active is bound to its cofactor, Targeting protein for Xklp2 (TPX2), preventing dephosphorylation and degradation . AURKA interacts with the IκB kinase (IKK) proteins, of which there are two active kinases, IKKα and IKKβ and a 3rd family member, IKKγ (NEMO - NF-kappa-B essential modulator), that acts as a scaffolding protein to form the prototypic IKK// complex [2,3]. Scanning peptide arrays approaches enabled IKK-AURKA protein-protein interactions to be identified. From this mapping an IKKβ-derived NEMO-binding domain (NBD) peptide in a cell-permeable peptide (CPP) form, also known as an inhibitor of canonical NF-κB activation, was identified to accelerate AURKA dephosphorylation/degradation through mitosis and had a similar effect on TPX2 status. Here, by using different pharmacological and molecular tools, we sought to elucidate the mechanism of NBD peptide-mediated dephosphorylation and degradation of AURKA.
PC3 (Human Caucasian prostate adenocarcinoma) cells were treated with Nocodazole (50ng/ml; 16-18h) to arrest cells at prometaphase and thereafter exposed to IKK small molecule (SM) kinase inhibitors, or CPP NBD treatment, as appropriate. Cells were also pretreated with small-interfering RNA (siRNA) prior to exposure to nocodazole. Samples were then prepared and analysed by either Western blotting or fluorescence-activated cell sorting (FACS) analysis. Data represents mean±SEM (n experiments) and analysis was performed using one-way ANOVA with post-hoc Dunnet’s test. Statistical significance was defined as p<0.05 unless stated otherwise.
NBD CPP Wild-type (WT) accelerated Aurora A dephosphorylation through mitosis post release from nocodazole arrest compared to the mutant-type, inactive (MT) peptide – 30 mins (54±5.1 vs 95.8±9.2 (%expression), n=3), 1h (39.6±10.1 vs 85.7±8.3 (%expression), n=3) and 2h (41.6±10.6 vs 14.7±2.8 (%expression), n=3). Similarly, TPX2 degradation was also accelerated through mitosis; 1h (50.2±14.1 vs 76.2±11.9 (%expression), n=3) and 2h (41.5±15.6 vs 56.4±7.2 (%expression, n=3). In contrast, SM kinase inhibitors and siRNA targeting IKK/ had minimal effect upon AURKA and TPX2 status
The NBD-derived peptide can pharmacologically modulate AURKA and TPX2 status. This appears to be independent of IKK kinase activity and protein expression, suggesting a potential novel allosteric mechanism of targeting elevated AURKA-TPX2 activity in cancer