分子バイオマーカーと診断のジャーナル

Aim: Breast cancer in women younger than 35 years old is uncommon and only accounts for 2% of all breast cancers diagnosed in Western countries. However, there is paucity of data on breast cancer in women younger than 35 years old in India. The aim of this study was to assess clinicopathological parameters in these young breast cancer patients.

Methods: This retrospective study summarized data on women younger than 35 years with breast cancer between August 2012 and July 2013 from tertiary cancer center in India.

Results: Out of a total of 320 patients, 36 were younger than 35 years old in this period of time and the median age was 32 years. A breast lump was the most commonly presented symptom with an average symptom duration of four months. The median age of the first childbirth was 22 years. Most of the patients had a stage III disease (52%) followed by stage II (33%). All patients had invasive ductal carcinoma and 86% of patients had high-grade tumors. 51% of patients were lymphnode-positive, and lympho vascular emboli were present in 43% of cases. Estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) positivity occurred in 38.9% and 22.2% of patients, respectively and 50% of patients were triple negative.

Conclusion: Breast cancer occurring in women younger than 35 years old constituted 11.3% of all breast cancer cases in Kidwai Memorial Institute of Oncology, India. They had high tumor grade with a larger size and an increased incidence of lympho vascular emboli, which lead to aggressive behaviors and poor prognosis. This study suggest that early onset of breast cancer must be considered as a diagnostic possibility in Indian patients presenting palpable masses in the mammary glands.

Cyclins and Cyclin dependent kinases (CDK’s) are proteins which act as positive regulators of the cell cycle at its various check points. The different cyclins attain peak activity during different phases of cell cycle and Cyclin D1 regulates transition from G1 to S phase of mitotic cell cycle. Due to this crucial role in cell cycle regulation, cyclins play an important role in carcinogenesis. Deregulated or over-expression of Cyclin D1 may lead to shortening of G1 phase, increased cell proliferation and reduced dependency on growth factors leading to disturbance in the normal cell cycle control and tumour formation. This short communication is a brief review about its role in head and neck carcinomas.

Plant secondary metabolites (SM), which frequently occur as glycosides, constitute large pool of structures which are valuable for medicinal chemistry and molecular pharmacology because of their inherent biocompatibility. Despite rich ethnopharmacological tradition of their application, glycosides as individual chemical entities are not very frequent as therapeutic agents, and their bulk availability is usually low. The current potential of chemical synthetic methods of glycosylation is discussed, in context of structural diversity needs in contemporary drug discovery programs. Newly designed procedures for glycosylation, which rely on transition metal catalysis, together with already established methods of chemical ligation (click chemistry), are well suited for elaboration of new semisynthetic SM libraries based on chemical glycosylation and glycorandomization principles

Acute pancreatitis is an inflammatory disease of pancreas with varied clinical presentation ranging from mild self limiting disease to severe necrotising pancreatitis with high mortality. The exact pathogenesis of the disease is unclear despite extensive research. Recent studies have shown the role of oxidative stress in the pathogenesis of the disease. Many experimental studies have proven the role of oxygen free radicals in the initiation and progression of the disease. Antioxidant therapy has shown promising results in experimental animal models, whereas conflicting result has been seen in clinical studies in humans. This may suggest existence of different pathogenetic mechanism in humans. This review gives an overview of the role of oxidative stress in the pathophysiology of acute pancreatitis and outcomes of antioxidant therapy as a therapeutic agent in the treatment of acute pancreatitis.

Although ionizing radiation has been used for treating a variety of human cancers, radiotherapy inadvertently results in the damage of normal tissues, functionally altering the immune system and being able to cause various organ specific autoimmune diseases. Macrophages and complements play pivotal roles in the clearance of the apoptotic cells, facilitating their opsonindependent phagocytosis and systemic clearance of apoptotic cells. SIGN-R1, a membrane bound C-type lectin expressed on the splenic marginal macrophages, mediates a classical but Ig-independent complement activation pathway by interacting with C1q, and SIGN-R1 and complement factors might play the integral role in the clearance of radiation-induced apoptotic cells. Also, DC-SIGN, the human homolog of SIGN-R1 on dendritic cells and macrophage subpopulations, directly binds to C1q, probably providing an initiation site for the classical complement pathway in the presence of a pathogenic surface. Autoimmune diseases are becoming a serious public health problems and there is increasing evidence that C-type lectins and complement system are involved in the pathogenesis of the autoimmune diseases. Therefore, further works are required to identify the existence of diverse membranebound C-type lectins that could mediate complement activation against apoptotic cells in vivo and its involvement in the pathogenesis of the autoimmune diseases.

Introduction: Early diagnosis of cancer can dramatically increase healing probability. However many cancer detection methods are time-consuming, invasive, and require skilled medical staff and/or expensive detection systems. Cervical cancer is the fourth most common malignant disease among women, and the fourth leading cause of cancer death in women worldwide.

Aim: This pilot study sought to identify reliable biomarkers indicative of early stages of cervical dysplasia, by analysis of changes in volatile organic compound composition in urine samples.

Methods: Urine samples of 17 patients with cervical intraepithelial neoplasia (CIN I) and of 9 healthy female subjects were used. The sample composition was analyzed using Gas-Chromatography-Mass-Spectrometry. The statistical analysis of the data was performed using supervised artificial neural networks.

Results: We identified four molecules with potential to serve as biomarkers of cervical dysplasia together with two molecules whose absence in the urine can confirm existence of cervical dysplasia. All indications shows that these six potential biomarkers are produced in the body during various physiological processes enhances in sick women. Hence, these potential biomarkers are not related to environmental or dietary origins.

Conclusion: Validation of the statistical method used, indicated that the biomarkers identified are highly reliable for detection of cervical dysplasia.

A 27 year old male diagnosed with psychosis, who was treated with Risperidone followed by aripiprazole was reported to present with adverse effects. Hence the therapy was changed to Blonanserin. It is a dopamine serotonin antagonist which has got fewer propensities to cause tardive dyskinesia (TD) than conventional antipsychotics and other atypical antipsychotics. This is a report on blonanserin induced hypokinesia followed by TD in the form of perioral tremors in a mid-aged male patient diagnosed with psychosis. There have been no reports on TD induced by blonanserin. Clinicians must be aware of the possibility of the patients developing hypokinesia and TD when they are treated with the supposedly safe atypical antipsychotics like blonanserin.

The analysis of volatile organic compounds [VOCs] is an attractive approach to the discovery of potential cancer biomarkers due to its non-invasive nature and potential low costs of sampling and analysis. Solid phase microextraction [SPME] is one of the main extraction techniques used to date for the collection of VOCs from both in vivo and in vitro samples in studies of potential biomarkers of various types of cancer. It offers simplicity of use, compatibility with both gas-chromatography [GC] and liquid-chromatography [LC] separation techniques and relatively lower costs. Development of the SPME method includes several important considerations: selection of the sampling mode, type of fiber and holder, optimisation of incubation, extraction and desorption conditions, and finally the use of an appropriate calibration procedure. This review summarizes and discusses the particular parameters of the SPME method development used by researchers to date for VOCs collection, from various biological matrices, in search of potential biomarkers of cancer.

The aberrant expression of N-glycolyl GM3 ganglioside (NeuGcGM3) has been reported in a variety of malignant tumors. Nevertheless, the relationship between NeuGcGM3 expression and aggressive biological behavior still remains unclear for the majority of malignancies. In this article the tissue reactivity of the 14F7 monoclonal antibody, a highly specific IgG1 against NeuGcGM3, in breast cancer, urinary bladder tumors and malignant gliomas of adult patients is shown as well as its relation with the histological grade of these malignancies. The expression of NeuGcGM3 was detected in 92/155 (59.3%) of tumors independently of the histopathological classification. However, a preferential expression of NeuGcGM3 was detected in: infiltrating ductal carcinoma (77.1%) vs. infiltrating lobular carcinoma (15.9%) (p=0.024), grade III (94.9%) vs. grade II (77.8%) and grade I (63.8%) transitional cell carcinoma (p=0.042) and high-grade astrocytomas (78.6%) vs. low-grade astrocytic tumors (10.0%) (p=0.026). The results achieved suggest the relationship between the tissue expression of NeuGcGM3 and the more aggressive biological behavior of these malignancies, regardless of the tumor cell lineage. The data obtained also support the continuous use of NeuGcGM3 as a target for immunotherapy in malignancies expressing this molecule as well as that of 14F7 monoclonal antibody for the selection of candidate patients for these specific therapies.

Type 2diabetes mellitus (T2DM) is the most common metabolic disorder worldwide. Because of population aging and increasing trends toward obesity and sedentary lifestyles, the number of affected individuals is increasing at worrisome rates. While both environmental and genetic factors are known to contribute to the development of T2DM, continuous research is needed to identify specific biomarkers that could aid both in prevention of the disease and development of newer therapeutic options. Circulating miRNAs are considered as potential biomarkers because they are stable and resistant to degradation by blood RNAses and are modified under different pathophysiological conditions. In this study we carried out a systematic electronic search on PubMed to retrieve all articles that have investigated circulating miRNAs for diagnosing obesity andT2DM in human. We also included lifestyle intervention studies known to be highly effective in delaying onset of diabetes, and studies analyzing the effect of bariatric surgery and anti-diabetic treatment. A total of 26 studies were enrolled in the global meta-analysis. Candidate miRNAs were defined as those reported in at least 2 studies with same direction of differential expression. Ten miRNAs altered in blood of patients suffering fromT2DM were identified (increased: miR-320a, miR-142-3p, miR-222, miR-29a, miR- 27a, miR-375; decreased: miR-197, miR-20b, miR-17, miR-652) and 7 miRNAs in blood of obese subjects were identified (increased: miR-142-3p, miR-140-5p, miR-222; decreased:miR-21-5p, miR-221-3p, miR-125-5p, mir-103- 5p). Both obese and T2DM patients had elevated concentrations of miR-142-3p and miR-222. MiRNAs target genes were predicted and their cellular functions are discussed in relation with the pathologies. Although a significant number of studies were taken into account in this review, we founda strong discrepancy between miRNA detection and quantification indicating that many of pre-analytical variables have yet to be normalized. Pre-analytical and analytical challenges are also discussed.

Introduction: While early-stage lung cancer is curable by surgical resection, most patients are diagnosed with advanced- stage disease. Annual low-dose computed tomography screening decreases lung cancer mortality, however effective biomarkers to address the high false positive rate and to better define high risk individuals are lacking. This study was designed to identify potential DNA methylation markers for the detection of non-small cell lung cancer, the most common type of lung cancer.

Methods: 152 candidate methylation genes were first investigated in lung cancer cell lines and a pilot set of lung tissues. Five promising methylated genes, DMRTA, HOXA9, ZIC4, HOXA7, and SIX3, were selected and further validated in 150 non-small cell lung cancers and 142 tumor-free surrounding lung tissues using the quantitative methylation-specific PCR.

Results: Methylation levels of DMRTA2, HOXA9, ZIC4, HOXA7, and SIX3 were significantly higher in tumors compared to tumor-free surrounding lung tissues (P<2.2e-16 for all). Receiver operation curve analysis showed that methylation of DMRTA2, HOXA9, ZIC4, HOXA7, and SIX3 identified 93%, 91%, 89%, 81%, and 59% of non-small cell lung cancers (n=150) with a specificity of 95%. Comparing tumors to tumor-free surrounding lung tissues, area under the curve values were 0.967, 0.955, 0.950, 0.904, and 0.819, respectively. The predicted area under the curve value after combining DMRTA2 and HOXA9 was 0.971. Methylation levels of these genes were not correlated to cancer stages (P>0.05).

Conclusion: We identified a group of highly sensitive and specific methylation markers in non-small cell lung cancer. These markers are potential valuable candidates to improve the performance of lung cancer screening.

Introduction: Gastric cancer (GC) remains a major public health problem worldwide being the third commonest cause of cancer death worldwide. Many recent studies focus on the immunohistochemical evaluation of Bcl-2 expression and its serum expression and its prognostic significance in gastric cancer each one separately. We conducted our study to determine the correlation between serum Bcl-2 antigen and gastric carcinoma, to investigate whether serum Bcl-2 concentrations can be used as marker for immunohistochemical determination of Bcl-2 alterations in gastric cancer patients and examine the association between its expression and other clinicopathological parameters.

Methods: Our study conducted in Forty-five consecutive patients with gastric cancer underwent gastrectomy in Mansoura Gastroenterology Center. ELISA was used for the estimation of serum Bcl-2 levels in patients with different stages of gastric cancer. Immunohistochemical localization of Bcl-2 antigen was performed on formalinfixed, paraffin-embedded tissue block; Bcl-2 expression was detected from mild to moderate apoptotic index (AI).

Results: Positive serum Bcl-2 expression was found in 13/45 patients (28.9%). Bcl-2 protein was immunohistochemically localized in the cytoplasm of 45% (18/40) of gastric cancer patients. Total apoptosis positivity in Bcl2 detected immunohistochemicaly was detected in 45% (18/ 40) of cases; while total apoptosis positivity in serum expression of Bcl-2 was detected in 28.9% (13/ 45).

Conclusion: our current study demonstrated that the formation and growth of cancer is a complex process that requires further research in correlation with the results assessed between serum and immunohistochemical expression of Bcl-2 and with its role in the process of apoptosis.

Over the past decade, the use of saliva as an auxiliary diagnostic tool for biomarker detection has gained considerable acceptance as a non-invasive, inexpensive alternative to conventional serum method. In proteomics, the most promising technique which can be used for detecting salivary biomarker with sufficient resolving power is two-dimensional gel electrophoresis (2-DE) that provides a unique platform for the simultaneous separation of proteins in a complex mixture. However, as a fact most of the new scientists in developing countries are still facing problems with optimization of 2-DE techniques because the performance of optimization techniques in proteomics research using 2-DE has its own limitations. Therefore, the present study was established to generate a reproducible and optimized protocol to display the 2-DE protein map of human saliva. Our results showed the standard optimization of the 2-DE protein mapping was achieved at pH 3-10 with 60 μg proteins loading. This protocol could be used by other scientists along with identification of differentially expressed proteins by mass spectrometry when 2-DE protein map of patients saliva are compared to that of normal healthy individuals. These differentially expressed proteins could be later used as specific and sensitive biomarkers for early diagnosis and prognosis of the disease in question. In conclusion, the procedure used in our study generated a highly reproducible and optimized reference 2-DE protein mapping of human saliva.