Evaluation of a new flow cytometry based method for detection of BCR-ABL1 fusion protein in chronic myeloid leukemia.

BACKGROUND: Philadelphia chromosome, a hallmark of chronic myeloid leukemia (CML), plays a key role in disease pathogenesis. It reflects a balanced reciprocal translocation between long arms of chromosomes 9 and 22 involving BCR and ABL1 genes, respectively. An accurate and reliable detection of BCR-ABL fusion gene is necessary for the diagnosis and monitoring of CML. Previously, many technologies, most of which are laborious and time consuming, have been developed to detect BCR-ABL chimeric gene or chromosome. METHODS: A new flow cytometric immunobead assay was used for detection of BCR-ABL fusion proteins and applicability, sensitivity, reliability, efficacy and rapidity of this method was evaluated. RESULTS: From February 2009 to January 2014, a total 648 CML patients were investigated for the status of BCR-ABL1 protein. Among them, 83 patients were enrolled for comparative study of BCR-ABL1 positivity by three routinely used procedures like karyotyping, and quantitative real time PCR (RT-PCR) as well as immunobead flow cytometry assay. BCR-ABL protein analysis was found consistent, more sensitive (17% greater sensitivity) and reliable than the conventional cytogenetics, as flow cytometry showed 95% concordance rate to RT-PCR. CONCLUSION: BCR-ABL fusion protein assay using a new flow cytometric immunobead might be useful in the diagnosis and monitoring CML patients.

Antioxidative and anticarcinogenic activities of methylpheophorbide a, isolated from wheat grass (Triticum aestivum Linn.).

Methylphophorbide a (MPa) has been isolated from the ethanol extract of the wheat grass plant. Its antioxidative efficacy is evaluated by hydroxyl radical scavenging activities and reducing capacity which are significantly up regulated in comparison with aqueous extract of the plant. The compound shows iron-binding capacity where the Fe(2+) binds with MPa by two types of binding patterns with dissociation constants 157.17 and 27.89. It has antioxidative and cytotoxic effects on HeLa and Hep G2 cells. The cancerous cell survivability decreases with increasing concentration of MPa. These findings have provided evidence for the traditional use of the wheat grass plant in the treatment of cancers, oxidative stress and iron overloaded disorders.

Individualizing breast cancer treatment-The dawn of personalized medicine.

Identification of breast cancer not being a single disease but backed by multiple heterogeneous oncogenic subpopulations is of growing interest in developing personalized therapies to provide optimal outcomes. Through this review, we bring attention to evolution of tumor and microenvironment heterogeneity as a predominant challenge in stratifying therapies. Establishment of a 'precancer niche' serves as a prerequisite for genetically initiated cells to survive and promote neoplastic evolution towards clinically established cancer through development of tumor and its microenvironment. Additionally, continuous evolutionary interplay between tumor and recruited stromal cells along with many other components in the tumor microenvironment adds up to further complexity in developing targeted therapies. However, through continued excellence in developing high throughput technologies including the advent of single-nucleus sequencing, which makes it possible to sequence individual tumor cells, leads to improved abilities in decoding the heterogenic perturbations through reconstruction of tumor evolutionary lineages. Furthermore, simple liquid-biopsies in form of enumeration/characterization of circulating tumor cells and tumor microvesicles found in peripheral circulation, shed from distinct tumor lesions, show great promise as prospective biomarkers towards better prognosis in tailoring individualized therapies to breast cancer patients. Lastly, by means of network medicinal approaches, it is seemingly possible to develop a map of the cell's intricate wiring network, helping to identify appropriate interconnected protein networks through which the disease spreads, offering a more patient-specific outcome. Although these therapeutic interventions through designing personalized oncology-based trials are promising, owing to continuous tumor evolution, targeting genome instability survival pathways might become an economically viable alternative.

Breast cancer stem cells: a novel therapeutic target.

Breast cancer stem cells (BCSCs), characterized by the CD44(+)/CD24(-/low) marker, are attributed with features that are demonstrated by the disease itself, such as growth of tumor, recurrence, metastases, and multiple drug resistance. This review concerns the emergence and expediency of BCSCs in treating relapse and advanced cases of breast cancer. One of the ideal ways of detecting and eliminating BCSCs would be to tweak certain molecular receptors in the desired pathway, which would require extensive and comprehensive knowledge about these cell signaling pathways. Although hedgehog (Hh), Notch, and Wnt signaling are of prime concern, governing tumorigenesis and cancer stem cell (CSC) renewal, designing chemotherapeutic or molecular targeted therapies is still a tricky arena to venture into, as these pathways play a vital role in normal mammary gland development. Thus selective inhibition of pathway receptors needs to be investigated in the future.

Surveillance and expected outcome of acute lymphoblastic leukemia in children and adolescents: An experience from Eastern India.

OBJECTIVE: Research in Eastern India especially among children and adolescents for acute lymphoblastic leukemia (ALL) have not been well documented until recently when it was conducted at a cancer institute of tertiary care with primary objectives of examining and correlating different cell surface markers involved with respect to disease surveillance thereby highlighting it as a strong prognostic marker for future diagnosis and treatment. MATERIALS AND METHODS: A total of 500 consecutively selected ALL patients were diagnosed and treated according to National Cancer Institute protocol (MCP 841) for a period of 24-88 months during this hospital-based study. RESULTS: Of the total, 50.4% had a higher incidence of T-ALL and 47.6% had pro-B, B-cell precursor ALL. Disease free survival and event free survival were remarkably higher in B-ALL adolescent patients as compared to T-ALL, who had significantly lower overall survival ratio. Prevalence of T-ALL was also observed in relapse cases for adolescent patients. CONCLUSIONS: We conclude that there is an increased prevalence of T-ALL among adolescents in Eastern India. Immunophenotypic analysis might help in proper evaluation and prediction of treatment outcomes with an increased thrust on studying age-specific incident rates enabling well planned future treatments for improved and better outcome.

Trifluoperazine stimulates ionizing radiation induced cell killing through inhibition of DNA repair.

The effect of trifluoperazine (TFP), a phenothiazine derivative antipsychotic drug, on ionizing radiation (IR) induced cell killing through inhibition of DNA repair was investigated in human cell lines. In clonogenic survival assay, TFP augmented IR induced cell killing. Also, TFP enhanced micronucleus formation in irradiated human lymphocytes. The effect of TFP and other known DNA repair inhibitors like wortmannin and caffeine, on irradiated cells, was compared by MTT assay. On the other hand, TFP failed to increase the toxicity induced by H2O2. Repair of DNA double strand breaks induced by IR was markedly inhibited by TFP, as determined by field inversion gel electrophoresis (FIGE). Further, TFP increased radiation induced apoptosis, which was accompanied by enhanced G2/M arrest. Thus, our results strongly suggest that TFP inhibits repair of DNA damage induced by IR, which significantly implicates the possibility of using TFP as an adjuvant to radiotherapy.