Cancer immunotherapy: Benefit and harm?

In this article, evidence is reviewed suggesting that the outcome of cancer immunotherapy depends on pre-treatment immune parameters of a patient. The results described in the article show that immunotherapy may prolong survival in certain subgroups of cancer patients, while in other subgroups a cancer-promoting effect of this treatment modality cannot be excluded

TGF-β1 and TNF-α after red blood cell transfusion in colorectal cancer patients

Operations in patients with cancer are associated with blood transfusion to restore normal physiology. Blood transfusion can cause the immunomodulatory effect. There is lack of the literature data about influence of blood transfusion on the blood serum levels of cytokines TGF-β and TNF-α, though these cytokines are important in neoplasia development. The aim of our study was to estimate changes in the concentration of cytokines TGF-β1 and TNF-α in colorectal cancer patients’ peripheral blood after surgery and allogenic red blood cell transfusion. Methods: Venous blood of 64 patients with colorectal adenocarcinoma in stage III was tested before and after the surgery. Concentration of cytokines TGF-β1 and TNF-α was quantitatively measured by ELISA. Results: TGF-β1 and TNF-α concentration significantly increased in the group of transfused colorectal cancer patients (before operation: TGF-β 10.1 ± 1.3 ng/ml, TNF-α 20.9 ± 1.7 pg/ml and after operation and RBC transfusion: TGF-β 15.9 ± 1.7 ng/ml; TNF-α 27.0 ± 2.1 pg/ml). Statistical analysis has shown that serum levels of cytokines didn’t change significantly after surgery in non-transfused patients group. Conclusion: These results indicate that levels of multipotent cytokines TGF-β1 and TNF-α were elevated after red blood cell (RBC) transfusion in colorectal cancer patients.Операции больных онкологического профиля нередко сложные и сопровождаются переливанием крови для восстановления кровопотери. Данные литературы свидетельствуют о том, что переливание крови оказывает иммуномодулирующий эффект на организм пациентов. Однако существует недостаточно данных относительно влияния переливания крови на изменения концентраций цитокинов ТФР-β1 и ФНО-α, играющих важную роль в развитии опухолевой болезни. Цель: определение влияния переливания аллогенной эритроцитарной массы на изменения концентрации цитокинов ТФР-β1 и ФНО-α в периферической крови больных колоректальным раком после операции. Методы: концентрацию цитокинов ТФР-β1 и ФНО-α определяли методом ELISA у 64 больных раком толстой кишки III стадии до и после операции. I стадии до и после операции. Результаты: концентрация цитокинов ТФР-β1 и ФНО-α достоверно повышалась в периферической крови больных, которым после операции переливали аллогенную эритроцитарную массу (перед операцией: ТФР-β1 10,1 ± 1,3 ng/ml, ФНО-α 20,9 ± 1,7 pg/ml, после операции и переливания массы аллогенных эритроцитов: ТФР-β1 15,9 ± 1,7 ng/ml; ФНО-α 27,0 ± 2,1 pg/ml). Выводы: полученные результаты показали, что концентрация мультипотентных цитокинов ТФР-β1 и ФНО-α повысилась у больных колоректальным раком III стадии после переливания аллогенной эритроцитарной массы. I стадии после переливания аллогенной эритроцитарной массы

Targeted therapies in colorectal cancer: an integrative view by PPPM

In developed countries, colorectal cancer (CRC) is the third most common malignancy, but it is the second most frequent cause of cancer-related death. Clinicians are still faced with numerous challenges in the treatment of this disease, and future approaches which target the molecular features of the disorder will be critical for success in this disease setting. Genetic analyses of many solid tumours have shown that up to 100 protein-encoding genes are mutated. Within CRC, numerous genetic alterations have been identified in a number of pathways. Therefore, understanding the molecular pathology of CRC may present information on potential routes for treatment and may also provide valuable prognostic information. This will be particularly pertinent for molecularly targeted treatments, such as anti-vascular endothelial growth factor therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy. KRAS and BRAF mutations have been shown to predict response to anti-EGFR therapy. As EGFR can also signal via the phosphatidylinositol 3-kinase (PI3K) kinase pathway, there is considerable interest in the potential roles of members of this pathway (such as PI3K and PTEN) in predicting treatment response. Therefore, a combined approach of new techniques that allow identification of these biomarkers alongside interdisciplinary approaches to the treatment of advanced CRC will aid in the treatment decision-making process and may also serve to guide future therapeutic approaches

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer

Analysis and mathematical modelling of dynamics of two tumours system

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