Current Cancer Therapy Reviews - Volume 16, Issue 2, 2020

Colorectal cancer (CRC) is the development of cancer from the colon or rectum. This kind of cancer presents with a broad spectrum of neoplasms from benign to metastatic forms. The development of the majority of colon cancers appears from adenomatous polyps or adenomas systematically. At least three molecular pathways are involved in CRC pathogenesis including chromosomal instability (CIN), microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). Methods such as fecal occult blood tests (FOBTs), colonoscopy, flexible sigmoidoscopy (FOS), computed tomographic colonography (CTC), and fecal DNA are commonly used for CRC screening. The current review discusses the signs and symptoms associated with CRC, molecular pathways related to CRC and some strategies for current screening, diagnosis and treatment.

Cancer is a refractory disease, which brings physical, mental and economic sufferings on patients and their families. The activation of oncogenes and/or the deletion of tumor repressors result in uncontrolled tumor survival and proliferation. Therapeutic resistance and cancer recurrence are common issues during the course of clinical treatment. Since each single treatment can’t eradicate tumor cells completely, the development of combinatorial therapeutic regimen is in the spotlight for several decades. Combinatorial therapeutic regimen, a treatment modality that combines two or more therapeutic agents, targets key pathways in a characteristically synergistic or an additive manner. It aims to improve the efficacy and magnitude of therapeutic responses and reduce the likelihood of acquired resistance by using optimal drug dose with tolerable side effect. Currently, the combinatorial therapeutic regimen not only includes various chemicals, but also diverse therapeutic modalities which affected DNA damage repair, protein localization and degradation, post-translational modification, cell metabolism and apoptosis, as well as immune response.

Background: Radiotherapy is a commonly used cancer treatment modality. However, radiation-induced complications are major drawbacks, especially at high doses. Radiation-induced brachial plexopathy (RIBP) is mostly observed in breast and lung cancer patients some months to years after radiotherapy. RIBP symptoms have negative effects on patients’ quality of life. The aim of this study was to review RIBP according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Methods: Online databases (PubMed, Scopus, Web of Science and Embase) were searched to retrieve relevant studies on brachial plexopathy as a complication of radiotherapy. Results: Initial search results yielded a total of 657 articles. After careful screening of their titles and abstracts, according to the inclusion and exclusion criteria, 31 articles were finally included in this study. Findings from these 31 papers showed that a total of 9192 cancer patients had undergone radiotherapy for different regions including chest, axillary area, thoracic outlet, neck and breast. 26.4% of these patients had RIPB (associated with symptoms such as paresthesia, pain, weakness, and/or motor dysfunction, organ pathology/dysfunction etc.) with different follow up times, where 8.2% of patients had RIPB after a mean time of 1.2 years, 15.8% after 2.6 years, 51% after 5 years, 14% after 7.8 years, and 11% after 10.5 years. Conclusion: From our findings, we can conclude that the issue of radiation-induced brachial plexus complication in human is of great concern. Common symptoms associated with this complication include paresthesia, numbness, pain and weakness. We recommend the use of individual dose planning and computer-assisted image segmentation techniques that support rapid and reliable contouring of the brachial plexus. Also, the radiation dose to the brachial plexus should be limited as much as possible to reduce the risk of brachial plexopathy.

Background: DNA methylation plays an important role in the regulation of gene expression in mammalian cells and often occurs at CpG islands in the genome. It is more reversible than genetic variations and has therefore attracted much attention for the treatment of many diseases, especially cancer. In the present study, we investigated the effect of Solanum nigrum Extract (SNE) on the methylation status of the VIM and CXCR4 genes in breast cancer cell lines. Methods: The Trypan blue assay was used to study the effect of SNE at various concentrations of 0, 0.1, 1.5, 2.5, 3.5 and 5 mg/ml for 48 h on the survival of three human breast cancer cell lines MCF7, MDA-MB-468, MDA-MB-231. Methylation status of VIM and CXCR4 genes in breast cancer cell lines was assessed by Methylation-Specific PCR (MSP) method. Also, methylation changes of VIM and CXCR4 genes in breast cancer cell lines after treatment with 0.1 mg/ml of SNE for 6 days were analyzed by MSP method. To confirm the effect of SNE on methylation of VIM and CXCR4 genes, Real-Time PCR was performed. Results: The Trypan blue assay results indicated that treatment with SNE reduced cell viability in a dose-dependent manner in breast cancer cells. Our results showed that treatment of breast cancer cells with 0.1 mg/ml of SNE hypermethylated the VIM, CXCR4 genes and significantly reduced the expression levels of their mRNA (P<0.05). Conclusion: Our findings reveal for the first time the impact of SNE on the methylation of breast cancer cells.

Introduction: Pancreatic cancer consists of 10% of digestive tract tumors, and while rare, it is associated with high mortality. In this study, we collected the patients’ data including tumor location, metastasis, pathology type, demographic factors, risk factors, and clinical and laboratory profile at the time of diagnosis to find the relation between these factors and disease progression. Methods: This study includes all data from real charts of patients with a definitive diagnosis of pancreatic cancer, admitted to Ghaem, Imam Reza, and Omid hospitals from 2002 to 2013. All the data which were available in lab results, exams, and patient files, were used accordingly. Results: 348 pancreatic cancer patients entered the study. About 61.5% of the subjects were men. Mean age was 59.67±14.37 years. Main complaints were abdominal pain (42.53%), jaundice (13.79%) or both (37.07%). We found a positive history of cancer in the first-degree relatives of 3.7% of patients, with the most prevalent being gastric cancer (46.1%). Cigarette smoking (P<0.001), tobacco smoking (cigarette or hookah) (P<0.001), opium use (P<0.001), and alcohol consumption (P=0.01) were significantly higher in men rather than women. However, hookah smoking was significantly higher in women (P=0.003). The most prevalent comorbidities were diabetes mellitus (33%) and hypertension (27.8%). The most common location of pancreatic cancer was head of the pancreas (85.3%). The most common pancreatic tumor pathology was adenocarcinoma (92.8%) with the same quiet prevalence in both genders. (P=0.5), It occurred significantly more in patients over 45 years old (P<0.001). Also, 45.7% of these patients had distant metastasis and liver was the most common metastatic site (69.8%). Conclusion: The age range was between 40 and 80 years old. The most common chief complaints were jaundice and abdominal pain. The most common tumor location was head of the pancreas. Adenocarcinoma was the most common pathology. The liver was the most common metastasis site.

Background & Aims: The clinical value of alpha-fetoprotein (AFP) as a marker to detect early hepatocellular carcinoma (HCC) has been questioned owing to its low sensitivity and specificity. The purpose of this work was to investigate whether serum Wnt/β-catenin and DKK1 levels in chronic hepatitis C patients could be used as early predictors for the risk of HCC development. Methods: The study was conducted on 37 healthy controls, and 150 CHC patients were divided into three groups: CHC, liver cirrhosis (LC), and HCC patients. AFP, AFP-L3, β-catenin, and DKK-1 were assayed by ELISA. Results: Both β-catenin and DKK1 levels significantly increased (p < 0.001) in the HCC group in comparison to LC and CHC groups. The first cut-off value for DKK-1 was 253 pg/ml with 88% sensitivity and 86% specificity. The second was 301.5 pg/ml with 82 percent sensitivity and 100% specificity. The β-catenin cut-off value was 7.35 ng/ml with 80% sensitivity and 74% specificity. A positive correlation was observed between DKK-1 and β-catenin (r=0.491), DKK-1 and tumor size (r =0.616), and β-catenin and tumor size (r =0.472). Conclusion: DKK-1 and β-catenin may serve as predictors for the progression of CHC and LC into HCC.

Aim: The objective behind this present work is the development and characterization of silver nanoparticles from Dalbergia sissoo leaf extracts and the analysis of anticancer activity. Methods: Silver nanoparticles were prepared by using the aqueous solution of Dalbergia sisoo leaf extract and silver nitrate. The formation of nanoparticles was determined by the color change during the preparation of plant extract to metal ion in a fixed ratio. The prepared nanoparticles were then characterized by TEM, FTIR, DLS, XRD, and SEM. Silver nanoparticles were also evaluated for anticancer activity. Results: Synthesized silver nanoparticles were having good anticancer activity against MCF 7 cancer cell line as compared to the standard drug Doxorubicin. Conclusion: The particle size of nanoparticles was found to lie in the range of 10 to 50 nm.

Background: Bone marrow biopsy has become an integral part of leukemia diagnosis and its treatment. Several advancements are being made towards the analysis of digital images of biopsy samples. Recently, the FDA approved the procedures of digital health. In tune with that, digital image analysis has become propelled. With the advent of high-throughput technologies, the scientific community focuses on the red blood cells (RBCs) for early detection of cancer, including leukemia. The reasons are due to their abundance in peripheral blood and hence, easily accessible compared to the bone marrow biopsy procedure. High magnification and high-resolution electron microscopy-based ultra-structural analysis of RBCs already proved the utility of the hypothesis about a decade ago. However, in clinical set-up, electron microscopy-based procedures are the major bottleneck in the implementation of early detection of leukemia. Algorithm-based computer vision may be suitable to overcome this limitation. Methods: An intensive search with PubMed and Google for early diagnosis of leukemia through RBC light microscopic images was made. For this search, the image processing algorithm for RBC was also made in PubMed, IEEE Xplorer and Google; and the latest developments are noted. To fill the existing gap, a user-friendly MatLab coding is developed for automated analysis of RBC images. Result: RBC images from both normal and leukemia were analyzed with the developed code. Each RBC cells were analyzed individually for each sample of normal and leukemia. Therefore, in the output cellular characteristics namely, radius, perimeter, area, convexity and solidity were represented in a quantitative manner. Comparison of mean values between normal and leukemia groups for corresponding variables showed statistical significance. In the test run, data of 82 RBC cells from single leukemia sample when compared with the data of pooled data of normal samples also showed significant difference (P<0.05). Conclusion: Thus, the developed code successfully distinguishes between RBC cells of leukemia and normal. We hope that this RBC based developed code would be useful in identifying earlystage of leukemia in an individual patient; however, for this, ~100 RBC cells are needed to be analyzed. As the developed code is based on RBC based diagnosis therefore, may be applied to other cancers and if needed, further modification is possible due to availability of code. Thus, it is expected that the developed MatLab code may play a role in preventive oncology.