Targeting histone deacetylases for cancer therapy: Trends and challenges

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor / Comparação entre as alterações hematológicas e bioquímicas ocasionadas pela quimioterapia convencional e quimioterapia metronômica no tratamento do tumor venéreo transmissível canino

This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p<0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.(AU)

Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p<0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.(AU)

Comparison between hematological and biochemical changes caused by conventional and metronomic chemotherapies in the treatment of canine transmissible venereal tumor

ABSTRACT: This study aimed to report the hematological and biochemical changes caused by conventional and metronomic chemotherapies, using vincristine sulfate to treat canine Transmissible Venereal Tumor (TVT). Twelve dogs were selected, six of them for the group receiving conventional chemotherapy (G1), and six dogs for the group receiving metronomic chemotherapy (G2). The G1 group received vincristine sulfate once a week at the dose of 0.75mg/m² until the tumor had disappeared with treatment, and the G2 group was treated with vincristine sulfate three times a week at the dose of 0.25mg/m2 until the tumor had disappeared. Before and after chemotherapy treatment, hematological and biochemical blood tests were performed to evaluate the main alterations caused by both chemotherapeutic models. Dogs undergoing conventional chemotherapy had significant leukocyte changes (p 0.05), causing neutropenia and leukopenia. In dogs undergoing metronomic chemotherapy, leukocytes remained within the reference range. Half of the dogs in group G1 had normochromic, normocytic anemia. The only biochemical alteration observed was the increase of urea in group G2. Thus, metronomic chemotherapy for the treatment of TVT with vincristine sulfate proved to be an excellent method for treatment, with fewer adverse effects, especially in maintaining the leukogram of dogs within normal range and reducing the number of anemia in animals during treatment.

RESUMO: Esta pesquisa teve como objetivo relatar as alterações hematológicas e bioquímicas causadas pelo tratamento quimioterápico convencional e pela quimioterapia metronômica, utilizando-se sulfato de vincristina para o tratamento do tumor venéreo transmissível canino(TVTC). Foram selecionados 12 cães, sendo seis para o grupo que recebeu quimioterapia convencional (G1) e seis cães para o grupo que recebeu quimioterapia metronômica (G2). O grupo G1 recebeu sulfato de vincristina, uma vez por semana, na dose de 0,75mg/m2, até o desaparecimento do tumor e o grupo G2 foi tratado com sulfato de vincristina, três vezes por semana, na dose de 0,25mg/m2, até o desaparecimento do tumor. Antes e após o tratamento quimioterápico foram realizados exames hematológicos e bioquímicos sanguíneos para avaliação das principais alterações causadas pelos dois modelos quimioterápicos. Os cães submetidos à quimioterapia convencional tiveram alterações leucocitárias significativas (p 0,05), causando uma leucopenia por neutropenia enquanto nos cães, submetidos à quimioterapia metronômica, os leucócitos mantiveram-se dentro do intervalo de referência. A metade dos cães do grupo G1 tiveram uma anemia do tipo normocítica normocrômica. A única alteração bioquímica observada foi o aumento da ureia no grupo G2. Desta forma, a quimioterapia metronômica para o tratamento do TVT com sulfato de vincristina, demonstrou ser um excelente método para a cura do animal, com menores reduções de efeitos adversos, sobretudo, na manutenção do leucograma dos cães e na redução de animais com anemia.

Human Immunodeficiency Virus and Human papillomavirus in Immunopathology of Cervical Cancer

The field of cancer immunobiology has been fast expanding.The realms of cervical cancer and immunodeficiency interactingat the molecular level has been actively investigated. The roleof the Human papillomavirus and developement of cervicalcancer admist a background of immunodeficiency is reviewedfor the novelty of the interaction between the HPV inducedoncogenesis and the host cellular responses in HIV positivewomen.The review aims to revisit the subject and generateinterest and research on HPV induced oncogenesis with anultimate aim to prevent cervical cancer. Greater understandingof the molecular pathways that underlie progression of highgrade IN to invasive cancer would be of great importancein the identification of the genetic markers that are able toidentify the women who have a high risk of progression tocancer, and therefore in need of aggressive monitoring andtherapy to prevent the development of cervical cancer.

Mecanismos moleculares de las proteínas de choque térmico (HSPs) implicados en el desarrollo neoplásico / Molecular mechanisms of heat shock proteins (HSPs) involved in neoplasm development

Resumen Las proteínas de choque térmico (HSPs) son proteínas inducidas por la mayoría de eventos que generan estrés celular y se expresan en niveles elevados en una amplia gama de tumores, entre los que se incluyen el cáncer de seno, pulmón, próstata, colon, leucemias y estomago, entre otros; esta sobreexpresión está estrechamente asociada generalmente con una resistencia a las terapias establecidas, lo cual genera un mal pronóstico. Las HSPs están involucradas en todas las fases del desarrollo neoplásico, desde la proliferación, la anti-apoptosis hasta en la invasión y metástasis. Entre los mecanismos descritos por los cuales las HSPs incrementan la agresividad tumoral se encuentran la evasión de los estímulos pro-apoptóticos y la respuesta inmune, la pérdida de función de p53, la expresión de proto-oncogenes HER2 y c-Myc, la activación de plasmina y MMP2, entre otros; todos estos eventos cruciales para la tumorogénesis. De esta forma las HSPs se han convertido un objetivo prometedor para el diseño dirigido de fármacos anti-cáncer y estrategias de inmunoterapia.

Abstract The heat shock proteins (HSPs) are induced by cells stress and expressed at high levels in a broad range of tumors between including breast, lung, prostate, colon, leukemia and stomach cancer; this overexpression is closely associated with resistance to established therapies instituting a poor prognosis. The HSPs are involved in all cancer stages, from the proliferation, anti-apoptosis, even in invasion and metastasis. Within the mechanisms described by which the HSPs increased tumor aggressiveness and metastasis in some tumor types are evasion of apoptotic stimuli and immune response, loss of p53 function, increased expression of the proto-oncogenes HER2 and c-Myc, activation of plasmin and MMP2, all crucial to tumorigenesis. Thus, the HSPs have become targets for anti-cancer drug design and immunotherapy strategies.

Bases evolutivas y ecológicas de la carcinogénesis humana ¿cuestión de mala suerte? / Evolutionary and ecological bases of human carcinogenesis, a matter of bad luck?

El cáncer constituye un serio problema de salud a nivel mundial. Las estimaciones, en cuanto a incidencia y mortalidad, no son nada halagüeñas, en especial para los países subdesarrollados. Durante las últimas décadas se han realizado importantes contribuciones a la comprensión de la carcinogénesis humana, sobre todo desde la perspectiva ecológica y evolutiva. Los objetivos del presente trabajo se centran en: destacar las principales hipótesis que desde dicha perspectiva, tratan de explicar la etiología de los tumores malignos, así como adecuar las que, a la luz de los hallazgos recientes o cotejadas con datos empíricos, parecen más factibles. La hipótesis tradicionalmente aceptada se basa en la carcinogénesis en múltiples etapas y explica de manera satisfactoria algunos aspectos del proceso; aunque conlleva a falacias de lógica, como la conclusión que dos tercios de los cánceres humanos obedecen a la mala suerte. Por su parte, la hipótesis de la oncogénesis adaptativa parece adecuarse de manera más realística a las complejas relaciones ecológicas que se establecen entre las células malignas, las células normales y el microambiente celular; capaces de originar fenómenos tan inadmisibles, como la cooperación de células normales en la progresión tumoral o la adopción por parte de las células malignas de estrategias evolutivamente estables. De hecho, la oncogénesis adaptativa incluso puede ser extendida al nivel del macroambiente poblacional y social. Su conclusión definitiva no hace más que reiterar la importancia de la prevención como la medida más eficaz para reducir la carga global de enfermedad por cáncer(AU)

Cancer is a serious health problem worldwide. Estimates, in terms of incidence and mortality, are not at all promising especially for underdeveloped countries. During the last decades, important contributions have been made to the understanding of human carcinogenesis, especially from the ecological and evolutionary perspective. The objectives of this work are focused on: highlighting the main hypotheses that, from this perspective, try to explain the etiology of malignant tumors, as well as adapting those that, in the light of recent findings or collated with empirical data, seem more feasible. The traditionally accepted hypothesis is based on multi-stage carcinogenesis; and satisfactorily explains some aspects of the process; although it leads to logic fallacies, such as the conclusion that two thirds of human cancers obey to bad luck. On the other hand, the hypothesis of adaptive oncogenesis seems to adapt more realistically to the complex ecological relationships established between malignant cells, normal cells, and the cellular microenvironment; capable of originating such inadmissible phenomena, such as the cooperation of normal cells in tumor progression, or the adoption by malignant cells of evolutionarily stable strategies. In fact, adaptive oncogenesis can even be extended to the level of the population and social "macroenvironment". Its final conclusion does nothing but reiterate the importance of prevention as the most effective measure to reduce the global burden of cancer disease(AU)

The oncogenic effects of p53-inducible gene 3 (PIG3) in colon cancer cells

The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear. Here, we found that PIG3 was highly expressed in human colon cancer cell lines compared to normal colonderived fibroblasts. Therefore, we attempted to elucidate the functional role of PIG3 in colon cancer. PIG3 overexpression increases the colony formation, migration and invasion ability of HCT116 colon cancer cells. Conversely, these tumorigenic abilities were significantly decreased in in vitro studies with PIG3 knockdown HCT116 cells. PIG3 knockdown also attenuated the growth of mouse xenograft tumors. These results demonstrate that PIG3 is associated with the tumorigenic potential of cancer cells, both in vitro and in vivo, and could play a key oncogenic role in colon cancer.

Evaluation of high-risk human papilloma virus infection inducing cervical cancer / 医学研究生学报

The oncogenic mechanism of human papilloma virus (HPV) has been elucidated,and high-risk HPV (HR-HPV) infection may cause malignancies such as cervical cancer.HR-HPV infection of the cervix is very common,while only a few cases of such infection develop into malignancy.Therefore,the evaluation of oncogenic risk of cervical HPV infection is of great clinical significance.Persistent HR-HPV infection of the cervix is mainly caused by immunological dysfunction-induced failure of HPV elimination and supposed to be the precondition of cervical cancer,while the type of HPV is an important factor for carcinogenesis of epithelial cells.

Research progress on HOTAIR in tumor biological behaviors / 中国肿瘤临床

Long non-coding RNA (lncRNA) is a cluster with over 200 bp in length and has no protein-encoding product RNA, which is in-volved in cellular physiological or pathological process, especially in human oncogenesis. HOX transcript antisense RNA (HOTAIR), which is 2158 bp in length, is one of the most well-studied lncRNAs. Overexpression of HOTAIR is correlated with oncogenesis or me-tastasis in numerous epithelium original human cancers, including breast and colorectal cancers. Inhibiting HOTAIR expression could suppress cell growth and invasive ability of tumors. This review provides a brief summary of the latest progress in lncRNA-based can-cer research.

Novel Therapy for Oral Cancer - Gene Therapy an Update.

Gene therapy provides modern medicine with new perspectives and had great potential as a novel therapeutic modality. Progress in molecular biology, especially molecular medicine is now changing the basics of genetic disease. This technology takes advantage of our understanding of cancer at the molecular level. It has been exploited to develop new strategies for killing cells selectively or arresting their growth. This is new technique, being developed which offers incredible pledge for the upcoming therapeutic modality in oral cancer treatment. The aim of this paper is to review delivery routes, vector design, therapeutic applications and possible obstacles faced by gene therapist.

Research progress of relationship between protein tyrosine phosphatase 1B and hematologic neoplasms / 白血病·淋巴瘤

Tyrosine phosphorylation is a key post-translational mechanism that regulates cellular processes and maintains homeostasis.Aberrant changes in tyrosine phosphorylation are often associated with disease states such as metabolicdisorders,cancer and cardiovascular disease.Protein tyrosine phosphatases (PTPs) are the enzyme family that regulates protein phosphorylation level of tyrosine residues in the cellular processes and signaling ways.So far,scientists have discovered 112 kinds of human PTPs.Among them,PTP1B is widely and clearly studied.Recently,as an enzyme that play a role in oncogenesis,PTP1B has been wildey studied by scientists.Here,we highlight the relationship between protein tyrosine phosphatase 1B and hematologic neoplasms.

Viral oncogenesis and tumor virotherapy / 白血病·淋巴瘤

After near a century of research,the diverse and complicated relationship between viruses and tumors has been elucidated gradually.Last century it was demonstrated that some retroviruses and some herpes viruses could induce lymphoma and leukemia in some animals.However,it is more complicated in human.During the last two decades it has been confirmed that several types of hepatitis viruses could cause hepatocellular carcinoma and the relationship between human papillomaviruses and cervix carcinoma has been established.These viral vaccines became useful tools to prevent prevalence of these carcinomas.Because of the successful inoculation of live attenuated viral vaccines all around the world in recent 15 years,oncolytic virotherapy is revived,and provides a novel strategy for treatment of refractory tumors.

Association of Endotoxins and Colon Polyp: A Case-Control Study

Endotoxins are known to be associated with the occurrence of various chronic diseases. This study was conducted to investigate the role of endotoxins in the pathogenesis of colon polyps through a case-control study. A total of 145 subjects (74 subjects in the polyp group and 71 subjects in the control group) had undergone a colonoscopy. Age, body mass index (BMI) and endotoxin levels were found to be significantly higher in the polyp group than in the control group. The endotoxin level was still significantly higher in the polyp group than in the control group, even after age and BMI had been adjusted (polyp group 0.108 +/- 0.007 EU/mL, control group 0.049 +/- 0.008 EU/mL, P < 0.001). In subgroup analysis, the endotoxin level significantly increased in accordance with the number of colon polyps (one-polyp group, 0.088 +/- 0.059 EU/mL; two-polyp group, 0.097 +/- 0.071 EU/mL; three-or-more-polyp group, 0.149 +/- 0.223 EU/mL). The endotoxin levels also significantly increased in groups with tubular adenoma with high-grade dysplasia (hyperplastic polyp group, 0.109 +/- 0.121 EU/mL; tubular adenoma with low grade dysplasia group, 0.103 +/- 0.059 EU/mL; tubular adenoma with high grade dysplasia group, 2.915 +/- 0.072 EU/mL). In conclusion, the serum level of endotoxins is quantitatively correlated with colon polyps.

COX-2 inhibitors: chemoprevention of head and neck cancer / Inibidores de COX-2: quimioprevenção de tumor de cabeça e pescoço

Objective: In addition to the well-established pathophysiological role that COX-2 plays in inflammation, recent evidence implies that this isoform may also be involved in multiple biologic events throughout the tumorigenic process. Many epidemiological studies demonstrate that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of a wide range of tumors. Further, COX-2 is chronically over expressed in many premalignant, malignant, and metastatic human cancers, and levels of over expression have been shown to significantly correlate to invasiveness, prognosis, and survival in some cancers. Conclusions: This article presents a broad overview of the growing evidence that COX-2 plays a pivotal role throughout oncogenesis and summarizes the rationale to explore the use of COX-2 inhibitors for the prevention or treatment of cancer as a single agent or in combination with current anticancer modalities. Epidemiological data and preclinical studies have generated compelling interest in the potential use of COX-2 inhibitors in chemoprevention and chemotherapy of human tumours.

Objetivos: Além do papel fisiopatológico bem definido que a COX-2 desempenha na inflamação, a evidênciarecente sugere que essa isoforma também pode estar envolvida em eventos biológicos múltiplos durante oprocesso de tumorigênese. Vários estudos epidemiológicos demonstram que anti-inflamatórios não esteroides (AINEs) reduzem o risco de uma grande variedade de tumores. Além disso, sabe-se que há sobre-expressãocrônica da COX-2 em muitos tumores humanos pré-malignos, malignos e metastáticos, tendo sido demonstradacorrelação dessa sobre-expressão com a invasão, o prognóstico e a sobrevida de alguns tumores. Conclusões:Este artigo apresenta uma visão ampla da crescente evidência de que a COX-2 desempenha papel fundamentalna oncogênese e resume os fundamentos para explorar o uso de inibidores COX-2 para a prevenção ou o tratamentodo câncer como um único agente ou em combinação com atuais modalidades anticancerígenas. Dadosepidemiológicos e estudos pré-clínicos têm gerado grande interesse no uso potencial de inibidores COX-2 naquimioprofilaxia e quimioterapia de tumores humanos.

Influence of CPG ODN on the down-regulation of pancreas cell line PANC-1 and the expression of TLR9 in human pancreatic cancer / 中华肝胆外科杂志

Objective To detect the expression of Toll-like receptor 9 (TLR9) in pancreatic cancer and to study the effect of CPG ODN2216 on the biological behavior of pancreatic cell carcinoma, and to explore their clinical significance. Methods Immunohistochemical method was used to examine the expression of TLR9 protein in pancreatic cancer tissue and immunofluorescence staining was also performed to detect TLR9 protein expression in pancreatic carcinoma cells. In vitro cell adhesion, wound-healing scrape assay, transwell invasion assay and cell colony formation assay were performed to assess the effect of CPG ODN2216 on the invasive properties of Panc-1 cells. Results TLR9 were highly expressed in the pancreatic cancer tissue and pancreatic carcinoma cells. In vitro experiments as cell spreading assays, cell adhesion, colony formation assay and invasion assays showed the cell adhesion and cell motility properties of CPG ODN 2216 group to be apparently weakened compared with the control group. MTT assay showed cell proliferation ability in the CPG ODN group to be notably decreased, and CPG ODN2216 had inhibitive effects on the growth of panc-1 cells in a dose and time-dependent manner. Conclusions TLR9 gene was correlated with the invasive and metastatic potentials of pancreatic carcinoma. The used of CPG ODN2216 induced the inhibition of migration and invasion of the Panc-1 cell line.

Cell Signaling in Viral and Oncogenic Pathogenesis and Its Implications in Disease Diagnosis and Prognosis / 中山大学学报(医学科学版)

Both viral diseases and cancer account for a large proportion of serious health problems.Viral infection and cancer are biologically and medically correlated and in many ways share common cellular pathways that lead to disease development or progression.Better understanding how these signaling events are specifically activated by different pathogenic stimuli and how they activate different downstream transcriptions in response to these stimuli at high specificity and efficiency will provide a new molecular basis for the development of novel disease biomarkers and therapeutic or preventive targets against both classes of diseases.Research in our laboratory has been prompted to investigate the regulation and modes of action of these pathways,with a more intensive focus on the NF-кB signaling,in the settings of severe or oncogenic viral infection as well as cancer development.It is hoped that our research will lead to eventual clinical application of biomarkers derived from these signaling pathways.

The Reciprocal Modulation Between Epigenetic and microRNA and The Application for Treatment of Malignant Tumors / 生物化学与生物物理进展

The recent investigations have demonstrated that epigenetic such as DNA methylation and histone modification was closely associated with cell growth and malignant tumors, and epigenetic modification was responsible for an important cause of oncogenesis. However, for the recent years some observations have been also shown that the development of tumorigenesis was attributed to transformation expression in microRNA. The latest investigations have revealed that epigenetic was involved in modulation of microRNA expression, on the contrary some kinds of microRNAs could also control epigenetic, moreover, the reciprocal modulation between microRNA and epigenetic could regulate gene expression and induce tumorigenesis. At the same time the data likewise displayed that epigenetic adjusted microRNA expression principally in a way of DNA methylation or histone modification, nevertheless microRNA regulated epigenetic by way of methyltransferases expression, DNA methylation maintenance and histone modification. With regard to the reciprocal modulation between microRNA and epigenetic, a comprehensive and systemic review of reciprocal relationship in modulation of cell growth and oncogenesis was gived.

Papel del gen TP53 en la oncogénesis / Role of the gene TP53 in the oncogénesis

La oncogénesis comprende múltiples etapas que incluyen cambios dinámicos en el genoma ocasionados por diversos factores que afectan principalmente dos grandes grupos de genes: los genes supresores de tumores (GST) y los protooncogenes. ambos intervienen en diferentes e importantes procesos biológicos como la proliferación y diferenciación celular. Dentro de los GST se destaca el gen TP53 que codifica para una fosfoproteína nuclear de 53kD, la cual actúa como factor de transcripción y regula positivamente la expresión de diferentes genes de vital importancia en varios mecanismos celulares: control del ciclo celular, apoptosis, replicación y reparación del ADN, como también en el proceso de envejecimiento. Este gen conocido como "guardián del genoma", ha sido ampliamente estudiado desde su identificacíon y se encuentra alterado en cerca del 60% de todos los tumores; además, tiene notable interés para el diagnóstico y pronóstico de pacientes con cancer.

Oncogénesis is a multistep process including genomic dynamic changes induced by diverse factors mainly affecting two gene great groups: the tumor suppressor genes and proto-oncogenes. Both take part in different and important biological processes as cell proliferation and differentiation. Among the tumor suppresor genes, the gene TP53 ancodes for one 53kD nuclear phosphoprotein wich acts as trnascription factor regulating positively the expression of different and very important genes mediating several cell mechanisms, such as control cell cycle, apoptosis, DNA replication and repair. This gene, aso known as "guardian of genomic integrity", has been extensively studied and has been fond altered in near 60% of all tumors; in addition, it has remarkable interest for the diagnosis ond prognosis of cancer patients.

Dectection of Ureaplasma urealyticum in Invasive Cervical Cancer Tissue / 대한산부인과학회잡지

OBJECTIVE: Mycoplasmas have been implicated in many diseases including cervicitis, urethritis, salpingitis, endometritis... and functioning as cofactors catalyzing the HIV disease state. The oncogenic potentiality of mycoplasma was only recently realized when they were shown causing chromosomal changes and in vitro cell transformations through gradual progressive chromsomal loss and translocation. Few study has been reported the prevalence of mycoplasma infection in human cancers and suggested that there was a connection between these organisms and human cancers. The objective of this study was to determine the relationship between Ureaplasma urealyticum infection and cervical cancer. METHODS: The detection frequency of Ureaplasma urealyticum in 52 invasive cervical cancer tissues and 17 normal cervical tissues was studied using PCR. RESULTS: U. urealyticum DNA was detected in 8 out of 52(15.4%) invasive cervical cancer tissues and 1 out of 17(5.9%) normal cervical tissues. No statistic significance was observed between the detection frequency of Ureaplasma urealyticum and clinicopathologic parameters. The prevalence of Ureaplasma urealyticum in invasive cervical tissues was 15.4% and this rate was higher than 5.9% in normal cervical tissues but there was no statistic significance. CONCLUSIONS: With respect to clinicopathologic parameters of cervical cancer, there was no significant relation between U. urealyticum infection and cervical cancer. There is, however, few study and case on cervical cancer internally and externally. It is considered that more studies on the subject with much cases should be made.

Increased Expression of Phospholipase C-gamma1 Activator Protein, AHNAK in Human Lung Cancer Tissues / 결핵

BACKGROUND: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate(PIP2) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate(IP3) and diacylglycerol. PLC-gamma1, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-gamma1 have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by IP3, phosphatidic acid, etc. Very recently, another PLC-gamma1 activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-gamma1 activator, AHNAK, in lung cancer specimens and their paired normal. METHODS: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract. Immunohistochemical stain was performed with primary antibody against AHNAK protein. RESULTS: Twenty-two among twenty-eight lung cancer tissues showed over expression of AHNAK protein(eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomal). the resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot. CONCLUSION: The overexpression of PLC-gamma1 activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-gamma1 act in concerted manner in carcinogenesis.