Current Cancer Therapy Reviews - Volume 15, Issue 3, 2019

Background: The immune system is designed with great care to distinguish self from non-self, as exhibited by immune responses to different pathogens. Furthermore, the immune system has the capacity to distinguish between self from altered self in case of autoimmune diseases like cancer. Developing tumors bypass the immune system mechanism which restrains selfreactive responses. Immunotherapy is a coherent means since the immune system can eliminate a number of antigens derived from the genetic constitution of B and T lymphocytes. Our understanding of the immune system has developed a great deal. Conclusion: This review is focused not only on the mechanism by which the immune system protects us but also on the ways in which it can inflict the body and how to modulate it with therapy. Thus, understanding the interaction of a tumor with the immune system provides insights into mechanisms that can be utilized to elicit anti-tumor immune responses. Here, we have recapitulated the function of the tumor microenvironment and immune checkpoints.

Blocking angiogenesis represents a fundamental process in Colorectal Cancer (CRC) treatment. VEGF (vascular endothelial growth factor) pathway is implicated in various processes that regulate tumor vascularization and proliferation. In the last years, great efforts have been made thanks to the discovery of targeted drugs that block VEGF and its receptors conferring a benefit in a variety of tumors, including CRC. To date, four drugs have been approved for the treatment of metastatic CRC (mCRC): bevacizumab, aflibercept, ramucirumab and regorafenib. Unfortunately, patients relapse due to the appearance of resistance. The VEGF family, its role in the angiogenesis and complex heterogeneity of mechanisms that escape tumor blockade are not completely understood and there is a lack of biomarkers of response to anti-angiogenic drugs. We describe the principal mechanisms of resistance to anti-VEGF therapy and discuss potential biomarkers to be investigated in the near future.

In order to try to increase the effectiveness of cancer therapeutic procedures, natural carotenoids attract lots of attention. Crocetin is one of the main carotenoids of saffron whose anticancer properties have been shown in recent decades. This study aimed to review previous in vitro and in vivo investigations on anticancer effects of this carotenoid and also proposed molecular mechanisms of its action. Literature reviewing between 1990 and 2017 was performed using pubmed and scopus databases. Anti-proliferative and pro-apoptotic effects of crocetin have been observed in several cancers cell lines and also model organisms that might be due to the alternation in the expression of cancer-related genes and epigenetic changes. Moreover, several studies indicated synergistic effects of crocetin with common chemotherapy agents and mentioned it as a potential novel adjuvant therapy.

Background: Androgen receptor (AR) upstreams complex signaling pathways that regulate cell proliferation and contribute to breast tumorignensis. Several clinical trials were initiated to investigate the clinical relevance of targeting AR especially in hormone-receptor-negative breast cancer. Methods: The search was performed in PubMed and the meeting libraries of ASCO, ESMO, SABCS, ImpakT congresses from January 2005 to July 2017. The following key words were used: Breast cancer, Androgen receptor, androgen agonist/antagonist, Flutamide, Abiraterone, Bicalutamide, Enzalutamide, Enobosarm, selective androgen receptor modulator. Results: Screening of title/abstracts yielded a total of 20 relevant results. Of those, twelve studies were found eligible: eleven clinical trials along with one case report. Response rates ranged from 0 to 12% while clinical benefit rates reached up to 35% in 2 studies (with enzalutamide and enobosarm). Progression-free survival ranged from 2.8 to 4.5 months. The most widely used cutoff for AR expression was 10%. High expression of AR was associated with more clinical benefit. Regarding safety, anti-androgens were generally well tolerated with hot flushes, elevated transaminases and fatigue being the most commonly reported across all agents. Conclusion: Androgen receptor pathway targeting in advanced breast cancer remains a valid option with reasonable clinical benefit in non-selected patients. Future studies are needed to define an AR addicted cohort with better responses and outcome.

Introduction: The prevalence of leukemia in children aged under 19 years continues to increase. Nutritional and environmental factors have been described as causes of their development, and maternal breastfeeding, birth weight, exposure to cow’s milk or to contaminants before 1 year of age, and smoking have been studied. Objective: To analyze the main nutritional and environmental risk factors in children with Acute Lymphoblastic Leukemia (ALL) in a public hospital in Guanajuato, Mexico. Methods: Analytical and cross-sectional study on 30 children under 18 years of age, with a confirmed diagnosis of ALL in a public hospital in Guanajuato, Mexico. With the signed informed consent of the children’s parents, a questionnaire was applied that collected and in which nutritional risk factors (weeks of gestation and birth weight, breastfeeding, exposure to cow’s milk) and environmental factors (smoking and exposure to arsenic) were evaluated. The frequencies and Odds Ratios (OR) of the main nutritional and environmental risk factors were obtained. Results: Mean age was 8 ± 4 years with 38 ± 1 weeks of gestation, with a birth weight of 3,200 g (range, 2,500-4,800 g). Fifty percent of the children consumed cow’s milk during their first year of life (40% before 6 months of age); 33.3% received maternal milk for ≤6 months and 63% of the parents had a positive smoking habit, with 66.6% of the participants living in cities with arsenic levels falling outside of the norm. Conclusion: The main nutritional and environmental risk factors found were early complementary feeding, cow’s milk prior to 1 year of age, a duration of breastfeeding of fewer than 6 months, birth weight of >3,500 g, a positive smoking habit in the children’s parents, as well as exposure to arsenic in drinking water. Identification of these risk factors could constitute an input for integrating novel prevention alternatives and the nutritional management of leukemia.

Background: Various models are used for brain tumors modeling. To our knowledge, no earlier work has been done on modeling the heterogeneous brain tumor that causes dizziness. However, specifying a cell using a model is not new. Unlike all earlier works in this regard, which consider analog or analog-CPU computers in the cell model, the model presented in this work fully utilizes processor computers. Materials and Methods: The purpose of this study is to offer a comprehensive approach for heterogeneous modeling of brain tumor cells. The model uses a brain tumor cell in Matlab and Simulink 3D software. Two heterogeneous models are presented for brain tumor cells: the imagebased cell model and computer-generated cell model. The image-based cell model is obtained through the figure altering on X-ray or ocular figures by recognizing the dissimilar states in the tumors. Results: The computer-generated cell model works based on locating computer produced aggregate cells into tumors. Some subdivisions for both the image-based and computer-generated cell models are presented as well. Conclusion: The positive and negative points of the image-based cell models and computergenerated cell models some scientific advices are presented in this work. Generally, the imagebased cell models could offer analytical facts for each state, but they are expensive and timeconsuming; besides, their performance is heavily influenced by deformation techniques. The computer-generated cell model, on the other hand, provides a higher cost of production and simplicity, but its main contribution is the overall performance and accuracy.

Background: Tumors of the childhood are considered to be grave and devastating pathologies, with high mortality rates. Current therapeutic options like cytotoxic drugs and radiotherapy target both healthy and malignant cells, thus resulting in long-term neurological and intellectual sequelae and endocrinological disorders. Objectives: In this study, we focused on the anticancer potency of crocins, the main constituents of Crocus sativus L, stigmas. Crocins were first extracted using organic solvents from the dried stigmas and then were identified using the HPLC analysis. Materials and Methods: TE-671 cells were treated with the extract of crocins using a range of concentrations between 0.25-mg/ mL and 16 mg/mL. Viability of the cells was measured at 24h, 48h, 72h and 96h. In addition, we have examined the expression levels of the p53 gene using Real-Time Reverse Transcription PCR. Results: Results showed that crocins exerted significant cytotoxic and anti-proliferative effects in a concentration and time - dependent-manner on TE-671 cells. Furthermore, p53 manifested similar expression pattern as the anti-proliferative effect of crocin. Conclusion: Our data demonstrate that crocins could be a novel promising agent for the improvement of tumor treatment.

Background: HER2 is a member of the human epidermal growth factor receptor (HER/EGFR-/ERBB) family. Amplification or over-expression of this oncogene has been shown to play a major role in the development and progression of certain destructive types of breast cancer. Several drugs like Trastuzumab, Pertuzumab, Capecitabine, and Letrozole are used in the patients with metastatic breast cancer that overexpress the HER2 receptor. Materials and Methods: We aimed to investigate, the prevalence, ADME prediction, biological activity prediction of novel HER2/ EGFR mutations in breast cancer. Literature review shows that pyrano pyrimidin scaffold plays important role in the treatment of Brest cancer. So we have to design novel 6,7-Dihydropyrano [2,3-d] pyrimidin-5-one derivatives with virtual screening techniques. Molecular target prediction shows that all derivatives act on tyrosine kinase. Results: Among all the compounds H11 (-8.8 kcal/mol), H2 (-8.7 kcal/mol), H15 (-8.6 Kcal/mol), and H17 (-8.7 Kcal/mol) had a maximum binding affinity as compared to Cipecitabine (-6.0 kcal/mol), STD1 (-7.2 Kcal/mol) and STD2 (-7.9 Kcal/mol) and other derivatives. Most of the compounds are moderately active and do not cross the blood brain barrier. Conclusion: The bioactivity prediction shows that all compounds are active to moderately active. These positive results show that it could be further investigated and explored.

Background: The “Hygiene Hypothesis” was postulated by David Strachan in 1989 to explain for the rapid 20th century increase in allergic diseases such as asthma. In this hypothesis, children from developed countries living in ultra-hygienic environments and avoiding exposure to viruses, bacteria, and parasites, especially helminthes, have an increased risk of atopic disorders. Materials & Methods: Research and online content related to cancer hygiene hypothesis is highlighted and to illustrate key themes. Guidelines for meaningful participation in DOC activities for people with diabetes, families, health care providers, and industry are provided. Results: The lack of worms leads to failure of stimulation of mucosal Th2 responses. These infections exert their effect through critically altering T-helper (Th)1/Th2 regulation, and it is postulated that, thus, they protect against atopy and asthma, through the induction of Th1 regulatory response. It is now also recognized that this “hygiene hypothesis” concept applies to a wider range of chronic inflammatory diseases than atopy and asthma, such as diabetes, multiple sclerosis and cancer. Conclusion: Here we discuss the major implications of these findings for the association between microorganisms and cancer, and also between some immune pathologies, like autoimmune diseases, and cancer.