Stem cell markers: A guide to neoadjuvant therapy in breast carcinomas

Aim: This study aims to investigate potential associations between the stem cell population and the degree of tumor regression in breast carcinomas treated with neoadjuvant therapy. Settings and Design: The study included 92 patients with breast carcinoma who received neoadjuvant therapy. Tumor regression was defined based on Miller and Payne grading system. Patients with grade 1 or 2 regression on a 5-point scale were included in group 1 (n = 37), grade 3 regression in group 2 (n = 32), and grade 4 or 5 regression in group 3 (n = 23). Materials and Methods: Immunohistochemical staining was performed on paraffin block sections of every case using CD44, CD24, CD29, CD133, ID4, and ALDH1 antibodies to detect stem cells. Statistical Analysis Used: IBM Statistical Package for the Social Sciences (SPSS), version 23.0 (IBM Corp., Armonk, NY, USA) software was used for statistical analyses, and a P value less than 0.05 was considered statistically significant. Results: Histologically high-grade tumors are more common in the near-complete/complete response group (P = 0.004). HER2-positive tumors were more common in the complete/near-complete response group (P = 0.054). Tumor cells positive for stem cell markers CD44 and CD24 were more common in the poor response group (P = 0.027 and P = 0.001, respectively). CD29 expression was reduced in the posttreatment residual tumor tissue in the near-complete/complete response group. Conclusion: High CD44 and CD24 expression may be a predictor of poor response/nonresponse to neoadjuvant therapy in breast carcinomas. Background: In recent years, stem cells have been defined as the main cell population responsible for resistance to anticancer therapies.

ROLE OF TUMOR MARKERS IN CERVICAL CARCINOGENESIS

Various types of tumor markers are currently being investigated to ascertain their capability in discriminating pre-cancerous lesions of cervix who have tendency for progression. The adequate treatment of such cases will check any chances of occurrence of carcinoma cervix in the population. The micro- RNAs are sensitive tumor markers but their high cost and sophisticated technique make them not feasible to be introduced in any cervical cancer screening program under Indian setup. Other tumor markers like claudins, p16, Ki67 etc are also very expensive. AgNOR pleomorphic counts and micronuclei counts are cheaper, the farmer being more reliable can be introduced in cytological screening program to identify high risk cases and can easily replace costly Human papilloma virus (HPV)- DNA testing.

Putative stemness markers octamer-binding transcription factor 4, sex-determining region Y-box 2, and NANOG in non-small cell lung carcinoma: A clinicopathological association

Background: The promising improvement in the clinical outcome of lung cancer can be possibly achieved by identification of the molecular events that underlie its pathogenesis. Cancer stem cell (CSC) being one of the subsets of tumor majorly participates in drug resistance and treatment failure because of the moderate cell cycle, lower proliferation, and increased expression of DNA repair and anti-apoptosis genes. Although many putative CSC markers exist, a precise characterization for non-small cell lung cancer is of utmost importance due to increased mortality rate and lack of targeted therapies. Hence, the article focuses on the expression of stemness-associated markers, namely octamer-binding transcription factor 4 (OCT4), NANOG, and sex-determining region Y-box 2 (SOX2) in non-small cell lung cancer (NSCLC) patients. Methods: The expression of OCT4, NANOG, and SOX2 were evaluated in 32 histopathologically confirmed NSCLC tissues using real-time polymerase chain reaction. The obtained expression was correlated with clinical and pathological manifestations using the statistical test such as Student's t-test and Pearson correlation in varied statistical software. Results: Results showed a significantly higher expression of OCT4 and NANOG compared to SOX2 in the tumor tissues. When the expression of these markers was correlated with the clinical parameters, higher expression was seen in males, patients with age above 60 years, and in adenocarcinoma subtype. In correlation with the habit, higher expression of OCT4 and SOX2 was observed in habituated patients. Expression of NANOG and OCT4 was higher even in patients with poor differentiation. Conclusion: The expression and prognostic significance of CSC markers obviously vary depending on histological NSCLC subtype. Importantly, our findings suggest that OCT4, SOX2, and NANOG network together may be promising for ongoing targeted therapies in specific NSCLC subgroups

Imaging methods of corneal neovascularization / 国际眼科杂志(Guoji Yanke Zazhi)

@#Corneal neovascularization(CNV)is a common cause of corneal diseases, but there is still no effective drug or treatment. At present, the common methods cannot inhibit the growth of CNV completely, cannot last for a long the therapeutic effect time, and there are also serious side effects, so the specific treatment of CNV inhibition is still being explored. The pathogenesis and treatment of CNV are the current research hotspots. CNV area is an important indicator to evaluate the efficacy of drugs and treatment regimens. There are multiple methods to develop CNV, including ink perfusion, immunofluorescence staining and so on, in recent years, optical coherence tomography(OCT)technology is also a potential new method. This article reviews the developing methods of CNV, hopes to provide a reference for the study of CNV.

Expression and clinical significance of stem cell markers CD44 and CD90 in ovarian cancer tissue / 国际检验医学杂志

Objective To study the expression and clinical significance of stem cell markers CD44 and CD90 in ovarian cancer tissue.Methods A total of 45 ovarian cancer patients received surgery resection were col-lected into the study group,45 patients received hysteromyomectomy were collected into the control group. Immunohistochemical method was used to detect the expression of stem cell markers CD44 and CD90 in the o-varian tissue of two groups,then the relationships between the expression of CD44,CD90 and 1 year survival rate were analyzed.Results The positive rates of CD44 and CD90 in the study group were 64.44% and 68.89%,which were significant higher than those of 0.00% and 0.00% in the control group.The positive rates of CD44 in tissues of clinical staging Ⅲ - Ⅳ stage,histological grade G2+G3 stage and with lymph node metastasis were 86.36%,88.46%,88.24% respectively,which were significant higher than 43.48%,31.58%, 50.00% inⅠ - Ⅱ period clinical stage,histological grade G1 phase and without lymph node metastasis.The positive rates of CD90 in tissues of clinical staging Ⅲ - Ⅳ stage,histological grade G2+ G3 stage and with lymph node metastasis were 90.91%,92.31%,88.24% respectively,which were significant higher than 47.83%,36.84%,57.14% inⅠ - Ⅱ period clinical stage,histological grade G1 phase and without lymph node metastasis,the differences had statistical significance(P<0.05).Follow-up was conducted for 45 cases of pa-tients with ovarian cancer,the survival rate of CD44 positive patients was 62.07%,less than patients with CD44 negative expression 87.50%,the survival rate of CD90 positive patients was 64.52%,less than patients with CD90 negative expression 85.71%,but the differences had no statistical significance(P>0.05).Conclu-sion T he expression of stem cell markers CD44 and CD90 might be involved in the occurrence and develop-ment of ovarian cancer,metastasis and infiltration process,and the expression level of the two markers could be used as clinical assessment of biological indicators of prognosis.

Problems and countermeasures in liver stem cell research and application / 第二军医大学学报

Stem cell has been one of the focuses in current biomedical research. It has been well documented that there are various liver stem cells (LSCs) with different markers in liver, and they play important roles in liver regeneration. Moreover, some progresses have been made in autologous and allogeneic stem cells transplantation for the treatment of end-stage liver diseases. However, the origin and markers of LSCs have not been fully clarified, and the mechanism involved in LSCs proliferation and differentiation remains to be deeply studied. With the improvements of lineage tracing technique and stem cell isolation and culture system, it is believed that the origin of LSCs and their role in liver regeneration will be further clarified, and LSCs treatment for liver diseases will soon become a reality.

Recent advances in breast cancer stem cell phenotypes and clinical application / 中国癌症杂志

The cancer stem cell theory suggests that cancer develops from a subset of tumor cells that possess characteristics of stem cells. Breast cancer stem cells comprise a sub-population, which possesses the capacity of self-renewal and the potential for differentiation and high tumorigenicity. Evidence from bothin vitro andin vivo studies demonstrates breast cancer stem cells are responsible for tumor relapse, invasion and metastasis, chemo- and radio-resistance and epithelial-mesenchymal transition (EMT). Herein, this review highlighted the recent advances in breast cancer stem cells.

Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.

Sports Anaemia in Endurance Athletes: A Physiological Phenomenon.

Endurance athletes require a very efficient oxygen transport system for maximal aerobic power during physical work performance. Many studies carried on endurance athletes suggested low levels of red blood cell markers leading to misconception of existence of so called sports anaemia in athletes. Sometimes athletes are on needless iron supplementation and are concern about anaemia. The main objectives of the study were to investigate the red cell population markers and to study the sports anaemia phenomenon in endurance athletes and the underlying responses responsible for ot. 60 male endurance track and field runners age group 18-21 were selected from the local city based club named Vasant Desai Krida Sangh Akola and were compared with the age, height sex matched non athletes students of Govt. Medical College Akola. The seven red blood cell markers were studied from the blood samples taken from the cubital vein under standard conditions. The blood variables for both the groups were analyzed with an automatic cell counter. The mean values of Hb(12.27 gm% +/- 0.782), RBC count in(3.64millions per cu mm+/-0.52), hematocrit ( 41.58 % +/- 1.32), mean corpuscular Hb conc (MCHC 29.49% +/- 1.198) were all very significantly lower ( p<0.0001) as compare to controls. Whereas the plasma volume (58.412% +/- 1.32), Mean Corpuscular volume (MCV 115.06 cu microns+/- 11.54)), Mean Hb conc (MCH 33.998 picogms+/- 2.608), were significantly increased in endurance athletes. Though decrease in Hb conc, Low RBC count and less hematocrit in endurance athletes indicate presence of anaemia in them but it’s not a true anaemia as it is also confirmed by MCV, MCH, MCHC values between the two groups. The significant differences between the groups are due to the response to endurance training leading to hemo dilutional anaemia caused by plasma volume expansion which increases the blood volume in endurance athletes helping them for better oxygen supply and aerobic power needed during physical work.

Application of MR stem cell markers in research of temozolomide intervention gliomas angiogenesis and therapy / 中国生化药物杂志

Objective To explore the role of MR stem cell markers in temozolomide intervention gliomas angiogenesis and therapy .Methods C6 glioma cells were intravenously injected in glioma model rat.MR stem cell markers and immunohistochemistry were used to observe the tumor growth and angiogenesis.Correlation of contrast imaging and immunohistochemistry results were studied.Results In this study, MR scanning was successfully used to trace the SPIO-PLL marked bone marrow stem cells, dynamic testing of angiogenesis in rat brain glioma tumor.Correlation analysis of imaging and immunohistochemical showed that they had a good negative correlation (P<0.05).Conclusion SPIO magnetic markers for bone marrow stem cells and MR tracing technique is an effective means of dynamic observation in vivo glioma angiogenesis.

Detection of embryonic stem cell markers in adult human adipose tissue-derived stem cells.

Background: Bone marrow transplantation is already an established therapy, which is now widely used in medicine to treat leukemia, lymphoma, and several inherited blood disorders. The culture of multilineage cells from easily available adipose tissue is another source of multipotent mesenchymal stem cells, and is referred to as adipose tissue-derived stem cells (ADSCs). While ADSCs are being used to treat various conditions, some lacuna exists regarding the specific proteins in these. It was therefore decided to analyze the specific proteins of embryonic cells in ADSCs. Aims: To analyze the specific protein of embryonic stem cells (ESCs) in ADSCs. Materials and Methods: Adult human adipose tissue-derived stem cells (ADSCs) were harvested from 13 patients after obtaining patients' consent. The specific markers of ESCs included surface proteins CD10, CD13, CD44, CD59, CD105, and CD166, and further nucleostemin,(NS) NANOG, peroxisome proliferator-activated receptor-gγ, collagen type 1 (Coll1), alkaline phosphate, (ALP) osteocalcin (OC), and core binding factor 1 (Cbfa1) were analyzed using by reverse transcription-polymerase chain reaction, (RT-PCR) immunofluorescence (IF), and western blot. Results: All the proteins were expressed distinctly, except CD13 and OC. CD13 was found individually with different expressions, and OC expression was discernable. Conclusions: Although the ESC with its proven self-renewal capacity and pluripotency seems appropriate for clinical use, the recent work on ADSCs suggests that these adult stem cells would be a valuable source for future biotechnology, especially since there is a relative ease of procurement.

Culture & characterisation of limbal epithelial cells & oral mucosal cells.

Background & objectives: Sources of autologous tissue that can functionally replace the corneal epithelium have been considered as an alternative to allogenous limbal transplants for limbal stem cells deficiency (LSCD). The aim of the present study was to compare the characterization of oral mucosa with limbal epithelial cells by markers using reverse transcriptase polymerase chain reaction (RT-PCR). Methods: Experiments were performed using oral tissue (n=6) obtained from patients who underwent oral mucosal graft for LSCD. Confluent cultures of limbus and oral mucosa epithelial cells were characterized by the pututative stem cell markers using RT-PCR. The morphological characteristics of cultivated epithelial cells were analyzed by haematoxylin and eosin staining and phase contrast microscopy. Results: Confluent sheets of epithelial cells were seen at the end of 14th day resembling the morphological features of limbal epithelia. RT–PCR analysis showed that cultured oral epithelial cells expressed markers such as ABCG2, p63, delta Np63, isoforms of p63, Keratin 3 (K3), membrane protein – Mucin (MUC 1, 4 and 16) and Antimicrobial Peptide - AMP (Human β Defensin – hBD 1, 2 and 3). Interpretation & conclusions: Oral epithelial cultures have morphological features resembling corneal and limbal epithelial cells by expressing similar marker genes. Thus, feasibility of clinical use of oral epithelial cells need be evaluated for allogenous limbal transplants.

Expression of embryonic stem cell markers in human term placenta / 대한산부인과학회지

OBJECTIVE: To determine which compartments of placenta in the term pregnancy express the embryonic stem cell markers. METHODS: We have used immunohistochemical methods with antibodies to embryonic stem cell surface antigens, TRA 1-60 (Tumor rejection antigen 1-60), TRA 1-81 (Tumor rejection antigen 1-81), SSEA-3 (stage-specific embryonic antigen-3) and SSEA-4 (stage-specific embryonic antigen-4), to identify and localize stem cells in the term placenta. RESULTS: Stem cell marker-positive cells were found in all layer of placenta. Amnionic epithelial cells was immunoreactive with TRA 1-60, TRA 1-81. Amnionic mesenchymal stromal cells was immunoreactive with TRA 1-81. Chorionic mesenchymal stromal cells was immunoreactive with TRA 1-60 and TRA 1-81. SSEA-3 and SSEA-4 were not stained at any compartment of the term placenta. Compartment that was stained most strongly by TRA 1-60 was the amnionic epithelial cells layer. Compartment that was stained most strongly by TRA 1-81 was the chorionic mesenchymal stromal cells layer. CONCLUSION: The mesenchymal stroma cells of the amnion and chorion as well as amnionic epithelial cells may be useful source of pluripotent stem cells in the term placenta.

Comparação entre as células-tronco de sangue de cordão umbilical de neonatos prematuros e nascidos a termo: uma revisão / Comparison between preterm and full-term newborn umbilical cord blood stem cells: a review

As células-tronco são células capazes de gerar diferentes tipos celulares. Entre as fontes de células-tronco encontra-se osangue de cordão umbilical que apresenta um grande número de progenitores hematopoéticos. Essa fonte vem sendo amplamente utilizada em transplantes devido a diversas vantagens, entre elas, a imediata disponibilidade, beneficiando pacientes com doenças hematológicas e imunológicas. Para o sucesso dos transplantes, há a necessidade de se considerar a freqüência das células-tronco nas amostras de sangue de cordão umbilical. Marcadores celulares específicos como a presença da molécula CD34 e a ausência de CD38 indicam o grau de imaturidade das células-tronco hematopoéticas e, conseqüentemente, a sua grande capacidade de proliferação e diferenciação celular. Existem diferenças quanto à freqüência das células-tronco no sangue de cordão umbilical entre neonatos nascidos a termo e prematuros. Essas diferenças podem ser importantes na escolha das amostras armazenadas nos bancos de sangue de cordão umbilical a serem utilizadas nos transplantes de células-tronco. Além disso, as pesquisas com células-tronco têm mostrado grande capacidade de proliferação e diferenciação em vários tecidos. O estudo das células-tronco pode ser a resposta para o tratamento de doenças cardíacas, neurológicas e imunológicas de inúmeros pacientes e, talvez, o primeiro passo para a cura.

Stem cells are cells that have the ability to give rise to different cell types. Among the sources of stem cells, there is the umbilical cord blood, which has a great number of hematopoietc progenitors. This source has been widely used in transplants owingto its advantages like, for example, immediate availability, improving patients with immunological and hematological diseases. In order for the transplant to be successful, it is necessary to consider the stem cell frequency within the samples of the umbilical cord blood. Specific markers like the presence of CD34 molecule and the absence of CD38 indicates the immature level of hematopoietic stemcells and consequently their ability of cellular proliferation and differentiation. There are differences between the cellular frequency in umbilical cord blood from preterm and term newborn. These differences might be important in order for finding a sample stored atumbilical cord blood banks for the transplant. Nevertheless, research using stem cells has attempted that these cells have a great capacity of proliferation and differentiatin into many tissues. Stem cell research offers hope for the treatment of cardiac, neurological and imunological diseases of countless patients and, perhaps, the first step to the cure.

Detection of illegal estrogen administration through immunohistochemical markers in the bovine prostate

The immunodetection of diverse cell markers was evaluated in prostatic samples from bullocks, and bullocks showing epithelial hyperplasia-metaplasia, with oestrogen-induced changes, and in experimental samples from bullocks inoculated with dietylstilbestrol (DES). Antigen-retrieval procedures allowed the use of tissues that had been fixed in formalin for long periods. Three tissue markers were chosen for the study: cytokeratins 13 and 16, vimentin and desmin. Monoclonal antibody K8.12 (specific for cytokeratins 13 and 16) stained basal cells and hyperplastic-metaplastic epithelium; monoclonal antivimentin, and desmin, allowed the definition of fibromuscular changes.

A imunodeteccão de marcadores celulares foi avaliada em amostras prostáticas de bovinos com hiperplasia ou hiperplasia-metaplasia epiteliais, induzidas por estrógenos administrados ilegalmente e em próstatas de bovinos inoculados com dietilstilbestrol (DES). A técnica de recuperacão antigênica permitiu o uso de tecidos fixados em formalina, por longos períodos. Foram utilizados os anticorpos monoclonais K8.12, anti-vimentina e anti-desmina para determinação de células basais coradas/epitélio hiperplásico-metaplásico, células do estroma e células musculares, respectivamente. As alterações tissulares observadas nos casos de campo e nos experimentais foram semelhantes, através do que se concluiu que houve administração ilegal de estrógenos. O teste imuno-histoquímico com esses marcadores específicos foi útil ao exame histológico da próstata, uma vez que a análise das imagens permite maior e melhor quantificação das alterações observadas. Os testes bioquímicos, entretanto, são necessários para uma avaliação mais precisa.