The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

OBJECTIVE: The purpose of this retrospective study was to assess the tolerability and efficacy of sequential chemotherapy and radiotherapy for the treatment of high risk endometrial cancer. METHODS: We conducted a retrospective study of previously untreated high risk endometrial cancer patients who received sequential chemotherapy and radiotherapy in accordance with the sandwich approach from June 2008 until June 2011. High risk endometrial cancer patients underwent complete surgical staging followed by adjuvant therapy encompassing sequential chemotherapy, radiation therapy and consolidation chemotherapy. RESULTS: The study analysis comprised 32 endometrial cancer patients. All subjects were treated with carboplatin and paclitaxel chemotherapy; currently, 186 cycles have been administered and 94% of patients have completed the planned number of cycles. Grade 3 neutropenia developed in 1 (3.1%) patient; there was no incidence of grade 4 neutropenia. Moreover, we observed grade 3 anemia in four (12.5%) patients and grade 4 anemia in one (3.1%) patient. One (3.1%) patient developed grade 3 thrombocytopenia; grade 4 thrombocytopenia was not observed. Five patients exhibited progressive disease, three of whom have since expired; mean progression free survival and follow-up were 17.4 months and 18.9 months, respectively. CONCLUSION: The preliminary results from our study suggest that the sandwich approach to treating high risk endometrial cancer patients is feasible. Hematologic toxicity was well tolerated and non-hematologic toxicity was mild and easily managed. Further study of this novel regimen in a larger patient population with extended follow-up is necessary.
Anemia ; Carboplatin ; Disease-Free Survival ; Endometrial Neoplasms ; Female ; Follow-Up Studies ; Humans ; Incidence ; Neutropenia ; Paclitaxel ; Retrospective Studies ; Thrombocytopenia

Introduction Worldwide, numerous studies have been conducted and many papers have been published about the impact of climate change on human health, and the correlations between air temperature, precipitation, droughts, and floods, and their adverse health effects such as respiratory and water-borne diseases. Scientific evidence on this issue continues to mount, showing that the effects of climate change are mostly adverse to human health. In Mongolia however, scientific research on the effects of climate change on health is at its starting point and only a few studies have been conducted. Goal Determine and assess risk factors and effects of climate change on human health Materials and Methods The study area included Zavkhan, Selenge, Dornod, Umnugovi aimags (provinces) and Ulaanbaatar city, each representing one of the five climatic zones of Mongolia. Daily meteorological variables for temperature, atmospheric pressure, wind speed, highest wind speed, precipitation and relative humidity of the selected study sites from 2009 to 2011 were acquired from the Institute of Meteorology, Hydrology and Environmental Monitoring. Statistical analysis of the collected data was done using the SPSS18 program and 95%CI was used to determine inter-zonal differences of weather and climatic variables. Results In order to determine climate risk factors, the analysis used the number of days when temperature exceeded mean annual air temperature by +25°С/-25°С, and their sequences, the number of days when the absolute temperature exceeded +30°С in summer months, and -30°С in winter months, and their sequences, the number of days when daily fluctuations in atmospheric pressure exceeded 30 hPa and the number of days when relative humidity was lower than 30 percent or greater than 80 percent, and their percentage of the total number of days.

Mannan-binding lectin (MBL) is a soluble innate immune protein that binds to glycosylated targets. MBL acts as an opsonin and activates complement, contributing to the destruction and clearance of infecting microorganisms. Hepatitis C virus (HCV) encodes two envelope glycoproteins E1 and E2, expressed as non-covalent E1/E2 heterodimers in the viral envelope. E1 and E2 are potential ligands for MBL. Here we describe an analysis of the interaction between HCV and MBL using recombinant soluble E2 ectodomain fragment, the full-length E1/E2 heterodimer, expressed in vitro, and assess the effect of this interaction on virus entry. A binding assay using antibody capture of full length E1/E2 heterodimers was used to demonstrate calcium dependent, saturating binding of MBL to HCV glycoproteins. Competition with various saccharides further confirmed that the interaction was via the lectin domain of MBL. MBL binds to E1/E2 representing a broad range of virus genotypes. MBL was shown to neutralize the entry into Huh-7 cells of HCV pseudoparticles (HCVpp) bearing E1/E2 from a wide range of genotypes. HCVpp were neutralized to varying degrees. MBL was also shown to neutralize an authentic cell culture infectious virus, strain JFH-1 (HCVcc). Furthermore, binding of MBL to E1/E2 was able to activate the complement system via MBL-associated serine protease 2. In conclusion, MBL interacts directly with HCV glycoproteins, which are present on the surface of the virion, resulting in neutralization of HCV particles.
Binding, Competitive ; Glycosylation ; Hepacivirus ; genetics ; pathogenicity ; physiology ; Humans ; Mannose-Binding Lectin ; metabolism ; Mannose-Binding Protein-Associated Serine Proteases ; metabolism ; Monosaccharides ; metabolism ; Protein Binding ; Protein Multimerization ; Tumor Cells, Cultured ; Viral Envelope Proteins ; metabolism ; Virion ; pathogenicity ; physiology ; Virus Internalization

OBJECTIVE: The risk factors associated with early ventral site hernia development following cancer surgery are ill defined and associated with an undetermined incidence. METHODS: We analyzed 1,391 gynecologic cancer patient charts to identify the number of post-operative ventral site hernias over a nearly 6 year period. The following study variables were noted for evaluation: patient demographics, disease co-morbidity (hypertension, cardiovascular disease, diabetes), body mass index (BMI), treatment (e.g., chemotherapy regimen), intra-operative (e.g., bleeding) and postoperative (e.g., infection) complications, time to hernia development and length of hospital stay. RESULTS: Twenty-six gynecologic cancer patients who developed a post-operative ventral hernia and subsequently underwent herniorrhaphy by our gynecologic oncology service were identified. The patient group's overall time to initial hernia development was 11.23 months. Following a multiple regression analysis, we found that treatment (e.g., bevacizumab, liposomal doxorubicin or radiotherapy associated with compromised wound healing [p=0.0186] and disease co-morbidity [0.0432]) were significant prognostic indicators for an accelerated time to hernia development. Moreover, five patients underwent treatment associated with compromised wound healing and also had disease co-morbidity. In this sub-group, post-operative hernia development occurred more rapidly (3.8 months) than the overall group of patients. BMI and age did not impact time to hernia development (p>0.05). CONCLUSION: In the present gynecologic cancer patient series, a tendency for early post-operative hernia development appeared to coincide with treatment associated with compromised wound healing and disease co-morbidity. Gynecologic cancer surgeons should anticipate this potential complication and consider employing prophylactic intra-operative mesh to potentially prevent this condition.
Antibodies, Monoclonal, Humanized ; Bevacizumab ; Body Mass Index ; Cardiovascular Diseases ; Demography ; Doxorubicin ; Hernia ; Hernia, Ventral ; Herniorrhaphy ; Humans ; Incidence ; Length of Stay ; Risk Factors ; Wound Healing

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
Genetic Predisposition to Disease ; genetics ; Genetic Testing ; Humans ; Kallikreins ; genetics ; Male ; Membrane Proteins ; genetics ; Prostatic Neoplasms ; diagnosis ; genetics ; Prostatic Secretory Proteins ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Risk Factors

Objective:Genotype-phenotype associations were studied in 517 subjects clinically affected by classical neuronal ceroid lipofuscinosis (NCL). Methods:Genetic loci CLN1-3 were analyzed in regard to age of onset, initial neurological symptoms, and electron microscope (EM) profiles. Results: The most common initial symptom leading to a clinical evaluation was developmental delay (30%) in NCL1, seizures (42.4%) in NCL2, and vision problems (53.5%) in NCL3. Eighty-two percent of NCL1 cases had granular osmiophilic deposits (GRODs) or mixed-GROD-containing EM profiles; 94% of NCL2 cases had curvilinear (CV) or mixed-CV-containing profiles; and 91% of NCL3 had fingerprint (FP) or mixed-FP-containing profiles. The mixed-type EM profile was found in approximately one-third of the NCL cases. DNA mutations within a specific CLN gene were further correlated with NCL phenotypes. Seizures were noticed to associate with common mutations 523G>A and 636C>T of CLN2 in NCL2 but not with common mutations 223G>A and 451C>T of CLN1 in NCL1. Vision loss was the initial symptom in all types of mutations in NCL3. Surprisingly, our data showed that the age of onset was atypical in 51.3% of NCL1 (infantile form) cases, 19.7% of NCL2 (late-infantile form) cases, and 42.8% of NCL3 (juvenile form) cases.Conclusion:Our data provide an overall picture regarding the clinical recognition of classical childhood NCLs. This may assist in the prediction and genetic identification of NCL1-3 via their characteristic clinical features.

Short-term outcome in very low birthweight babies has never been closely examined in Papua New Guinea. A cohort of neonates born over a year at Port Moresby General Hospital was followed from birth to death or discharge. Intrauterine growth retardation was an important contributor to low birthweight. Simple, inexpensive care resulted in respectable survival figures. Improving antenatal surveillance will have much more impact in reducing mortality in this group in the future than trying to emulate sophisticated and costly western neonatal care.
Antibiotic Prophylaxis ; Birth Weight ; Cohort Studies ; Exchange Transfusion, Whole Blood ; Female ; Fetal Growth Retardation - complications ; Respiratory Distress Syndrome, Newborn - therapy