Human dental pulp stem cells: Applications in future regenerative medicine

Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells(MSCs) from various human tissues,peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells(DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine.

Cetuximab plus irinotecan in pretreated metastatic colorectal cancer patients:The ELSIE study

AIM:To evaluate the efficacy and safety of cetuxim-ab plus irinotecan in irinotecan-refractory metastatic colorectal cancer (mCRC) patients from South-East Asia and Australia. METHODS:In this open-label,phase Ⅱ study,the main eligibility criteria were epidermal growth factor receptor-positive mCRC with progressive disease within 3 mo of an irinotecan-based regimen as the most recent chemotherapy. Patients received cetuximab 400 mg/m2 initially,then 250 mg/m2 every week,with the same regimen of irinotecan on which the patients had progressed (4 pre-defined regim-ens allowed). The prim-ary objective was evaluation of progression-free survival (PFS) at 12 wk. Secondary objectives included a further investigation of PFS,and an assessment of the overall response rate (ORR),duration of response,time to treatment failure (TTF),overall survival and the safety profile. RESULTS:One hundred and twenty nine patients were enrolled from-25 centers in the Asia-Pacific region and of these 123 received cetuximab plus irinotecan. The most common recent irinotecan regimen used was 180 mg/m2 every 2 wk which had been used in 93 patients (75.6%). The PFS rate at 12 wk was 50% (95% confidence interval (CI,41-59) and m-edian PFS tim-e was 12.1 wk (95% CI:9.7-17.7). The ORR was 13.8% (95% CI:8.3-21.2) and disease control rate was 49.6% (95% CI:40.5-58.8). Median duration of response was 31.1 wk (95% CI:18.0-42.6) and median overall survival was 9.5 mo (95% CI,7.5-11.7). The median TTF was 11.7 wk (95% CI:9.1-17.4). Treatment was generally well tolerated. The most common grade 3/4 adverse events were diarrhea (13.8%),neutropenia (8.9%),rash (5.7%) and vomiting (5.7%).CONCLUSION:In patients from Asia and Australia,this study confirm-s the activity and safety of cetuxim-ab plus irinotecan observed in previous studies in Europe and South America.

Circulating tumor cells: hope to diagnose and treat metastatic cancer

CHARACTERISTICS OF CIRCULATING TUMOR CELLS In 1869,Thomas Ashworth,an Australian physician,for the first time observed the cells which are morphologically identical to cancer cells in the blood circulation of metastatic cancer patients.Today,these cells are known as circulating tumor cells(CTCs).[1]Since most cancer deaths are associated with metastases,there is a need to study the exact mechanism of this cancer spread.

Role of circulating tumor cells in future diagnosis and therapy of cancer

Circulating tumor cells(CTCs)have become a blistering topic of discussion for oncologists because of their tremendous potential in the diagnosis and treatment of cancer.Over the past few years,they have been doled with quite an amount of research in this area understanding that CTCs are shed from tumors and circulate in the bloodstream.This process can also occur at an early stage of cancer.The major limitation in isolation of CTCs is their availability in limited numbers.Hence,many techniques have been developed and are under continuous improvement to enhance their effi cacy of CTC isolation and enumeration.They have shown their potentiality to not just indicate the presence of a tumor but also to provide us with its core information.They have also proven to be useful in detecting minor subgroups of cells present in the primary tissue which might eventually be the cause of treatment resistance or relapse of the disease.Hence,detecting and characterizing CTCs can defi nitely become an inevitable step in treating solid tumor malignancies.In this review,we have tried to comprehend the basics of CTCs including isolation,detection,characterization,and molecular mechanism of their circulation in the blood stream.We have mostly focused on the signifi cance of CTCs in diagnosis and therapies of four most common types of cancers,namely,breast,prostate,lung,and colorectal.This review provides the coverage of most of the advancements with regards to different tumor malignancies and their probable use in predicting outcomes of the disease to realize the concept of personalized medicine.

Profiling of circulating tumor cells in liquid biopsies from metastatic cancer patients

Aim:Circulating tumor cells(CTCs)are crucial to tumor metastasis and valuable for prediction of clinical outcome in patients with solid tumors.Here,the authors aimed to establish a method for enumeration and characterization of CTCs from liquid biopsies.Methods:Peripheral blood mononuclear cells(PBMCs)were separated from blood samples from patients with metastatic cancer using Ficoll-Hypaque gradients and cultured to isolate and enumerate CTCs.Cultured CTCs were morphologically characterized by light and phase contrast microscopy.The tumorigenicity of Ficoll-Hypaque-separated PBMCs was examined,in addition to their expression of mRNA metastasis markers.Results:CTCs were isolated in culture and enumerated by counting under phase contrast microscopy,demonstrating that 0.01-0.04%of total PBMCs were CTCs.CTCs were dormant,with large,oval-shaped,spiky morphology.PBMCs obtained from liquid biopsies exhibited anchorage-independent growth,forming numerous colonies in soft agar assays.Molecular profiling demonstrated expression of several metastatic genes,but not of cadherin 1(encoding the adhesion protein),in all patients.Conclusion:The authors successfully isolated,enumerated,and characterized CTCs from liquid biopsies of metastatic cancer patients.This study has potential to facilitate the development of new diagnostic and therapeutic methods using liquid biopsies,for application in metastatic cancers.

Evaluation of anti-metastatic effect of chitosan nanoparticles on esophageal cancer-associated fibroblasts

Aim:Esophageal cancer is one of the major types of cancers,causing death of approximately 5%of all cancer deaths.This is due,in large part,to both relatively ineffectual and unavailable treatment.In order to develop an effective treatment strategy against esophageal cancer,it is important to target metastatic genes.In the present study,we have used a cancer-associated fibroblast(CAF)cell line derived from culturing peripheral blood mononuclear cells from a metastatic esophageal cancer patient to see whether chitosan nanoparticles(Ch-Np)treatment can modulate the metastatic phenotype of CAF cells by using various cellular and molecular markers.Methods:A CAF cell line was developed from peripheral blood mononuclear cells(PBMC)from a metastatic esophageal cancer patient.The cells were treated with 100μg/mL of chitosan nanoparticle in vitro for the morphological and oncogenic characteristic studies,along with the expression of various genes involved in process of tumor development and metastasis.Techniques such as Light and Phase Contrast Microscopy,cell growth rate,Scratch metastatic assay,and molecular profiling were carried out to see changes in CAF cells before and after Ch-Np treatment.Results:It was observed that CAF cells grew in monolayer and had a doubling time of 25±0.38 h.Morphologically,the cells had a fibroblastic appearance.After treatment with 100μg/mL of Ch-Np in vitro,there was an increased doubling time to 30±0.83 h.Similarly,Scratch Assay showed an inhibition in the metastatic property of these cells.These findings were confirmed with gene expression studies.It was also observed that there was complete down-regulation of metastatic genes MMP1 and MMP9 and chemokines such as CXCR-4,CXCR-7,CCR-5,and SDF-1,indicating that Ch-Np inhibited the metastatic characteristic of CAF cells.Conclusion:This study has shown that there was an inhibition of metastatic properties of CAF cells after treatment with Ch-Np,suggesting that Ch-Np can be a delivery system used for targeting cancer cells for treatment of esophageal cancer.