Immunotherapy in gastric cancer

Gastric cancer is the second most common of cancerrelated deaths worldwide.In the majority of cases gastric cancer is advanced at diagnosis and although medical and surgical treatments have improved,survival rates remain poor.Cancer immunotherapy has emerged as a powerful and promising clinical approach for treatment of cancer and has shown major success in breast cancer,prostate cancer and melanoma.Here,we provide an overview of concepts of modern cancer immunotherapy including the theory,current approaches,remaining hurdles to be overcome,and the future prospect of cancer immunotherapy in the treatment of gastric cancer.Adaptive cell therapies,cancer vaccines,gene therapies,monoclonal antibody therapies have all been used with some initial successes in gastric cancer.However,to date the results in gastric cancer have been disappointing as current approaches often do not stimulate immunity efficiently allowing tumors continue to grow despite the presence of a measurable immune response.Here,we discuss the identification of targets for immunotherapy and the role of biomarkers in prospectively identifying appropriate subjects or immunotherapy.We also discuss the molecular mechanisms by which tumor cells escape host immunosurveillance and produce an immunosuppressive tumor microenvironment.We show how advances have provided tools for overcoming the mechanisms of immunosuppression including the use of monoclonal antibodies to block negative regulators normally expressed on the surface of T cells which limit activation and proliferation of cytotoxic T cells.Immunotherapy has greatly improved and is becoming an important factor in such fields as medical care and welfare for human being.Progress has been rapid ensuring that the future of immunotherapy for gastric cancer is bright.     

History of Helicobacter pylori,duodenal ulcer,gastric ulcer and gastric cancer

Helicobacter pylori(H.pylori)infection underlies gastric ulcer disease,gastric cancer and duodenal ulcer disease.The disease expression reflects the pattern and extent of gastritis/gastric atrophy(i.e.,duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis).Gastric and duodenal ulcers and gastric cancer have been known for thousands of years.Ulcers are generally non-fatal and until the 20th century were difficult to diagnose.However,the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present.It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century.Here,we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern,as it proved to be when it could be examined directly in the late 19th century.The environment before the 20th century favored acquisition of H.pylori infection and atrophic gastritis(e.g.,poor sanitation and standards of living,seasonal diets poor in fresh fruits and vegetables,especially in winter,vitamin deficiencies,and frequent febrile infections in childhood).The latter part of the 19th century saw improvements in standards of living,sanitation,and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent.In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for"surgical disease"or for"Sippy"diets.We show that while H.pylori remained common and virulent in Europe and the United States,environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H.pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H.pylori-related diseases.     

Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder

BACKGROUND: Recent data indicate high prevalence of both anxiety and substance comorbidity in bipolar disorder. However, few studies have utilized public sector samples, and only one has attempted to separate contributions of each type of comorbidity. METHODS: 328 inpatient veterans with bipolar disorder across 11 sites were assessed using selected Structured Clinical Interview for DSM-IV modules and self-reports. RESULTS: Comorbidity was common (current: 57.3%; lifetime: 78.4%), with multiple current comorbidities in 29.8%. Substance comorbidity rate was comparable to rates typically reported in non-veteran inpatient samples (33.8% current, 72.3% lifetime). Selected anxiety comorbidity rates exceeded those in other inpatient samples and appeared more chronic than episodic/recurrent (38.3% current, 43.3% lifetime). 49% of PTSD was due to non-combat stressors. Major correlates of current substance comorbidity alone were younger age, worse marital status, and higher current employability. Correlates of current anxiety comorbidity alone were early age of onset, greater number of prior-year depressive episodes, higher rates of disability pension receipt, and lower self-reported mental and physical function. Combined comorbidity resembled anxiety comorbidity. LIMITATIONS: This is a cross-sectional analysis of acutely hospitalized veterans. CONCLUSIONS: Distinct patterns of substance and anxiety comorbidity are striking, and may be subserved by distinct neurobiologic mechanisms. The prevalence, chronicity and functional impact of anxiety disorders indicate the need for improved recognition and treatment of this other dual diagnosis group is warranted. Clinical and research interventions should recognize these divergent comorbidity patterns and provide individualized treatment built "from the patient out."     

Evidence-based paediatrics

Evidence-based medicine is practised widely in some specialties and is now part of many undergraduate and graduate medical curricula. However, the extent to which it is used in clinical paediatric practice is not known and its expansion remains a major challenge. Access to technology which facilitates literature searching, and development of journals addressing specific paediatric problems, will encourage the use of evidence-based medicine by the busy paediatrician. Informed practice of evidence-based medicine will ensure that clinical expertise is complemented by a thorough search, evaluation and judicious application of relevant information from the medical literature.     

The relationship between posttraumatic stress disorder and smoking outcome expectancies among U.S. military veterans who served since September 11, 2001

Posttraumatic stress disorder (PTSD) is associated with increased rates of smoking although little is known regarding the mechanisms underlying this relationship. The current study examined expectations about smoking outcomes among smokers with and without PTSD. The sample included 96 veterans (mean age of 34 years) and included 17% women and 50% racial minorities. Smoking expectancies were measured with the Smoking Consequences Questionnaire-Adult (Copeland, Brandon, & Quinn, 1995). Consistent with previous work suggesting that smokers with PTSD smoke in an effort to reduce negative affect, unadjusted analyses indicated that smokers with PTSD (n = 38) had higher expectations that smoking reduces negative affect than smokers without PTSD (d = 0.61). Smokers with PTSD also had increased expectancies associated with boredom reduction (d = 0.48), stimulation (d = 0.61), taste/sensorimotor manipulation aspects of smoking (d = 0.73), and social facilitation (d = 0.61). Results of hierarchical linear regression analyses indicated that PTSD symptom severity was uniquely associated with these expectancies beyond the effects of gender and nicotine dependence. More positive beliefs about the consequences of smoking may increase risk of continued smoking among those with PTSD who smoke. Further understanding of smoking expectancies in this group may help in developing interventions tailored for this vulnerable population.     

Remodeling of the Extracellular Matrix of the Liver in Mice with BCG-Induced Granulomatosis after Administration of Liposome-Encapsulated Composition of Oxidized Dextran and Isonicotinic Acid Hydrazide

Bulletin of Experimental Biology and Medicine - Remodeling of the extracellular matrix of the liver in mice with BCG-induced granulomatosis after 2-month course of intraperitoneal injections of...