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Application of Proteomics in Cancer Study
Get PDFCancer is one of the most malignant diseases in the world, accounting for 7.6 million deaths (around 13% of all deaths) in 2008 based on WHO reports. Early detection of cancer is vital due to its final control and prevention. Despite advances in diagnostic strategies, they have not the required sensitivity and specificity for prognosis. During the last decays, one of the most challenges for cancer research is to determine biological basis of this malignancy as a characteristic agents for an early-stage cancer. Understanding these agents requires molecular level examination of the disease followed by analysis of protein networks and their interactions in cells, signaling events among cancer cells, interactions among the cancer cells, and the tumor microenvironment. Proteomics as one of the modern areas of biochemistry holds great promise in cancer study. Inasmuch as, proteome reflects the real state of a cell, tissue or organism, it is expected to achieve more accurate tumor markers for disease diagnosis and therapeutic monitoring. In fact, the utility of this innovative large-scale proteome analyzer has shown significant prospective in biomarker discovery, patient monitoring, drug targeting and cell signaling; moreover, advances in the field of proteomics will provide new insight into the molecular complexity of the disease process, and enable the development of tools to help in treatment as well as in detection and prevention. In this review, proteomics approaches in cancer studies have been represented and discussed
Anti-tumor Activity of Novel Compounds Targeting BCR-ABL, c-SRC and BCR-ABLT315I in Chronic Myelogenous Leukemia
Get PDFChronic myelogenous leukemia (CML) is a hematological stem-cell disorder characterized by the expression of the BCR-ABL fusion protein, a constitutively active tyrosine kinase that causes pathogenesis. The development of tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL oncogene has proven an effective approach to treat CML, but a non-negligible proportion of patients develop a resistance to this class of drugs. Of note, the T315I mutant of BCR-ABL is resistant to all known TKIs, with the noticeable exception of ponatinib. To address this unmet medical need, a new series of compounds was designed and tested for anti-tumor effects against BCR-ABLT315I CML. The effects of three OriBase Pharma compounds (OR1001, OR1002 and OR1003) on the kinase activity of wild-type and mutant BCR-ABL proteins, on cell proliferation and on the growth of subcutaneous xenografts of CML cells in athymic mice were investigated. In vitro, the three compounds were potent inhibitors of both ABL and c-SRC kinases and of the main mutants of ABL, including T315I. The three compounds inhibited the proliferation of cell lines expressing the wild-type and several mutated forms of BCR-ABL, including T315I. Finally, in a mouse xenograft model, OR1001, was found to significantly reduce tumor growth. These data support the potential of OR1001 as an effective therapy for the treatment of de novo and TKI-resistant patients
Undifferentiated High-grade Pleomorphic Sarcoma (Malignant Fibrous Histiocytoma ) Occurring in the Nerve Root: A Rare Case Report and Review of the Literature
Get PDFIntroduction: undifferentiated pleomorphic sarcoma (UPS) represents a group of pleomorphic mesenchymal neoplasms without any defined cell differentiation, occurs more commonly in the extremities. However, we report a rare case of UPS, not malignant peripheral nerve sheath tumor (MPNST) in which the nerve root of the forth cervical vertebrae and adjacent tissues were involved. Presentation of Case: Histopathologically, this tumor was composed of highly atypical spindle cells, pleomorphic cells and multinucleated giant cells. Nuclear mitoses were frequently observed. Immunohistochemistrical results showed that the tumor cells stained positively for vimentin but negatively for all the other immunomarkers.Conclusion: We here reported an extremely rare case of UPS arising from the nerve root of the forth cervical vertebrae and proposed a hypothesis “tumors without any expression of neural markers should be diagnosed as UPSs, not MPNSTs, even though which may arise from peripheral nerve branches”
Sulfotransferase 1A1 (SULT1A1) Polymorphism and Breast Cancer Risk: A Case-control Study in South India
Get PDFIntroduction: Breast cancer is the most common cancer among women worldwide. Sulfotransferase plays an important role in the formation of estrogen which is usually conferred as a risk factor for breast cancer. The SULT1A1*2 polymorphism is likely to play an important role in the susceptibility to breast cancer. This polymorphism (G638A) in the sulfotransferase 1A1 (SULT1A1) gene may causes Arg213His amino acid change and consequently results in significantly reduced enzyme activity and thermostability.Materials and Methods: In this case-control study, we investigated the role of SULT1A1 G638A polymorphism in breast cancer patients. We genotyped 144 patients with breast cancer and 116 healthy control subjects, using a Polymerase chain reaction –Restriction Fragment length polymorphism (PCR-RFLP) method.Results: The frequencies of SULT1A1 G638G, G638A and A638A were 83.5%, 17.8%, and 1.4% in the breast cancer group and 89.5%, 4.0% and 0.0% in the control group. The results of our study indicate that the SULT1A1 G638A genotype showed 4.6 folds increased risk of breast cancer (p = 0.002).Conclusion: In conclusion, our results suggest that, SULT1A1 G638A variant is significantly associated with risk of breast cancer in south Indian women
Statistical Comparison of Clinical and Histologic Diagnoses of Breast Tumours in Public and Private Hospitals
Get PDFBackground: Breast cancer is the leading cause of cancer deaths in Nigerian women. Most cases present in late or advanced stages with consequent poor prognosis. There are also instances of false clinical diagnoses with resultant patient adversity. Population screening based on genetics is largely unavailable to the citizens. Therefore, early diagnosis is the immediate choice available to the health system.Methods: Retrospective data were collected including all open-breast-biopsies submitted to three histopathology laboratories. The clinical and histologic diagnoses for each sample were compared. Statistical estimate of the accuracy of clinical diagnoses of breast cancer by clinicians was calculated using histologic diagnoses as the reference standard, and by calculating the sensitivity, specificity, false rates and odds ratio. Diagnostic accuracies of clinicians working in public and private hospitals were also compared in terms of these rates.Results: Our result showed that the diagnostic accuracy of the doctors working in public hospitals is more sensitive than that of those working in private hospitals. The overall false positive rate in both hospital groups combined is found to be high. This is probably due to unavailability of modern radiodiagnostic facilities that may otherwise enhance clinical assessment and diagnoses. The doctors in the public hospital group are generally more efficient in breast cancer diagnoses than those working in private hospitals.Conclusion: The authors believe that better funding of the audited hospitals, regular training of the medical personnel and provision of modern radiodiagnostic facilities may probably enhance clinical accuracy of breast cancer diagnoses in these hospitals
Total Antioxidant Capacity (TAC) in Patients with Haematological Malignancies in Niger Delta-region of Nigeria
Get PDFIntroduction: Haematological malignancies (HM) are malignant disorders involving the haemopoietic system. Oxidative stress has been implicated in the development and evolution of these disorders. To measure total antioxidant capacity (TAC) in patients with HM and to determine if any, the relationship between TAC and total lipid in these patients.Presentation of the case: This is a multicentre cross sectional study. Patients were sampled with self administered questionnaire that documented their biodata and the various types of haematological malignancies they had. Blood samples from 31 patients with HM and 11 controls were assessed for TAC and total lipids using RelAssay and TECO diagnostic kits respectively. Difference between means was compared using student T-test. The relationship between TAC and TL was measured using Pearson’s correlation coefficient.Total antioxidant capacity was significantly lower in patients with HM. The mean total lipid concentrations of the cancer patients were higher than in the controls but this was not statistically significant (p0.05). A negative correlation was found between TAC and total lipids in patients with HM.Conclusion: This study has further affirmed that patients with HM have a significantly lower antioxidant activity. However, further investigations are required to fully elucidate the mechanism and clinical implications of reduced TAC in these patients
Cellular Responses to Anthracyclines Identify Ku70, a DNA Repair Factor that Changes Compartment and Remains Stable in Leukemic Cells
Get PDFAnthracyclines such as doxorubicin and daunorubicin are anticancer drugs that act by damaging the DNA and used for treating a variety of cancers including adult acute myeloid leukemia. To date, nearly 50 % of acute myeloid leukemia patients show resistance to anthracyclines although the cause is not known. We first investigate if there is a relationship between the expression level of 23 DNA repair genes in three leukemic cell lines (KG-1, HL-60 and Mono-Mac1) and cellular responses to anthracyclines. We observed that the DNA repair genes were all downregulated in these cell lines following exposure to doxorubicin. Further analysis revealed that the general downregulation of the genes was linked to a substantial decrease in the recovery of total RNA raising the possibility that assessment of total RNA, and not specific gene or set of genes, can be used as a simple indicator of cellular responses to anthracyclines. Furthermore, examination of total protein extracts derived from these cell lines revealed for the first time that Ku70 is a key protein that remained stable, while the majority of proteins were loss, upon anthracycline treatment. Importantly, Ku70 redistributes from the cytoplasm to the nucleoli in a time-dependent manner in response to anthracycline exposure. We propose that Ku70 redistribution might play a vital role in predicting cellular response to anthracycline and promoting cell death
Evaluation of invitro Antimutagenic Potential of Lagenaria Siceraria Using Ame’s Test
Get PDFCancer is one of the most life-threatening diseases and widespread in both developed and developing countries. Accumulation of genetic alterations is main etiology for cancer developments. Many of the Cucurbitaceae plants possess antitumor activity traditionally. Methanolic extract of Lagenaria siceraria Standley Fruit was tested for their antimutagenic potential. The extract of plant exhibited varying level of antimutagenicity. Ames test was used in the current study to evaluate antimutagenic activity in TA98 and TA100 strains of Salmonella typhimurium using direct (Sodium azide) acting mutagens. Results of the study showed significant antimutagenicity against mutagen in TA98 and TA100 strains. The antimutagenicity of the extract observed in the present study implies chemopreventive pharmacological importance of Lagenaria siceraria Standley Fruit and encourages its use as a functional food
Socioeconomic Achievement Pressure Hypothesis: The Causal Environmental Mechanisms in Hodgkin Lymphoma Development
Get PDFThe Socioeconomic Achievement Pressure hypothesis is presented as the environmental cause of Hodgkin lymphoma across the human lifespan and across all ethnicities. This claim is supported by an almost complete coverage of the Hodgkin lymphoma epidemiology with this hypothesis. Based on this hypothesis I contend that the risk for Hodgkin lymphoma can be explained by excess achievement and intellectual pressure in specific individuals because they find it hard to fulfill or to comply with the high standards of socioeconomic and/or intellectual requirements of their family, community or peers. The prolonged and intense cognitive stress might ultimately lead to Hodgkin lymphoma development. Thus intellectual and cognitive stress appears to be the causal sociocultural mechanisms in Hodgkin lymphoma development.Cognitive and intellectual stress appear to cause deregulations of the lymphatic system. The experienced severity of cognitive stress determines what kind of lymphoma the patient will develop. Both intensity and the duration of exposure to cognitive stressors are crucial in lymphoma development. The personal characteristics of the patient are crucial to understand the incidence of Hodgkin lymphoma.Hodgkin lymphoma epidemiology also provides for the causal mechanisms how family dynamics really work. It also clarifies that sociocultural mechanisms rather than genetic explanations appear to be the causal mechanisms underneath the similarities in behavior and preferences of identical twins. This research provides important clues to conduct more thorough and conclusive research on twins, family dynamics and lymphomas in animals
Evaluation of Antibacterial Activity and Cytotoxicity of Green Synthesized Silver Nanoparticles Using Hemidesmus Indicus R.Br.
Get PDFIn this work, Silver nanoparticle with potent antimicrobial activity was produced by plant mediated green synthesis of silver nitrate. Characterization of silver nanoparticle revealed that nanoparticles were crystalline in nature. TEM analysis confirmed the spherical shape of nanoparticle billow 20 nm of size. X-ray diffraction analysis reveals that the silver nanoparticles are crystals. Investigation of the antibacterial properties of silver nanoparticles against gram positive S. aureus and gram negative P. aeruginosa offered a minimum inhibition concentration of 12.5 µg/ml for both the cases. In addition, silver nanoparticles were able to decrease the viability of both PA-1 cell line (derived from human ovary Teratocarcinoma), and A549 (human non-small cell lung alveolar epithelial cell line) in a dose dependent manner