bluuebunny/crossref_metadata_2025 huggingface dataset:
Espondilolistesis ístmica lumbosacra del adulto: laminoartrectomía y fusión in situ
Authors: Manzone Patricio , Ihlenfeld Claudia , Ávalos Eduardo Mariño , Gemetro José Felipe
Published: August 2012

OBJETIVO: La espondilolistesis ístmica del adulto se puede tratar con reparación del defecto, descompresión (sola o con fusión), fusión circunferencial, y reducción con fijación posterior. El objetivo de este trabajo es valorar los resultados a medio plazo de la descompresión y fusión in situ en pacientes operados por un solo cirujano. MÉTODO: Criterios de Inclusión: 1) Espondilolistesis Ístmica L5-S1. 2) Operados en madurez esquelética. 3) Laminoartrectomía de L5 con Artrodesis posterolateral instrumentada sin reducción. 4) Más de 3 años de seguimiento. 5) Ausencia de pseudoartrosis al seguimiento. 6) Valoración funcional y radiológica por observador independiente. Comparación de datos con bibliografía. Análisis estadístico con t - test, Chi cuadrado y ANOVA. RESULTADOS: 16 pacientes (12 ♀/4 ♂) evaluados. Edad promedio: 40,6 años (17 - 66); seguimiento promedio: 10.3 años (3.3 - 18). Deslizamiento promedio: 42,9%. Nueve presentaban dolor radicular, 3 dolor lumbar y 4 dolor lumborradicular. Score del dolor (SRS) preoperatorio promedio: 1.38, sin diferencias entre bajo y alto grado (p=0.887). 15/16 mejoraron (score final promedio: 4.44). 13/16 retornaron a su actividad previa (81%). Hubo 2 infecciones; no hubo complicaciones neurológicas. Los parámetros espinopélvicos finales, comparados con la literatura no mostraron diferencias estadísticas. La comparación entre listesis de bajo y alto grado en la serie no mostró diferencia significativa en dichos parámetros, ni en tiempo de seguimiento, niveles artrodesados, síntomas ni retorno al trabajo. CONCLUSIÓN: La descompresión y fusión posterolateral instrumentada in situ permite un 80% de buenos resultados en la espondilolistesis ístmica lumbosacra del adulto sin importar el grado.
Análisis comparativo de pacientes con estenosis degenerativa lumbar pura (EDLP) y estenosis secundaria a espondilolistesis degenerativa lumbar (ELDL) tratados quirúrgicamente en el período de 2008 a 2011 en el Hospital Metropolitano de Quito-Ecuador
Authors: Torre Sebas tián De la , Moyano Jaime , Ahtty Edison , Bilbao Madelin
Published: August 2012

OBJETIVO: Establecer si existen diferencias demográficas, de tratamiento y en resultados entre los grupos de EDLP y ELDL. MÉTODOS: Estudio retrospectivo observacional de 76 pacientes con EDL tratados quirúrgicamente. Se analizan por separado los datos demográficos y la evolución del grupo 1 (EDLP, 53 pacientes) y del grupo 2 (ELDL, 23 pacientes). RESULTADOS: Grupo 1: 51% mujeres y 49% varones. Edad promedio 56,8 años. Evolución preoperatoria 34 meses; Grupo 2: 78% de mujeres y 22% de varones. Edad promedio 63,4 años. Evolución preoperatoria 10 meses. Los dos grupos fueron intervenidos con la misma técnica, por el mismo equipo quirúrgico. El porcentaje de satisfacción postoperatoria fue mejor para el grupo 1 cuando el tiempo de evolución preoperatoria fue menor a 18 meses. En el grupo 2 los hallazgos no fueron significativos. CONCLUSIÓN: La estenosis por ELDL tiene características de edad y sexo muy diferentes dela EDLP. La cirugía precoz presentó un mayor porcentaje de satisfacción.
Dermatoglyphic Evaluation in Subjects and Parents of Cleft Lip with and without Cleft Palate
Authors: Saxena Runjhun Subhanand , David Maria Priscilla , Indira A.P.
Published: August 2012

Objectives

Dermatoglyphic patterns make good material for genetic studies because they remain stable throughout life. Given that the primary palate, lip, and dermal ridges develop during the same period of intrauterine life, the genetic message contained in the genome can be deciphered during this period and is reflected by dermatoglyphics. This study was undertaken to compare the dermatoglyphic patterns in subjects with clefts and controls and both their parents to study the genetic etiology.

Methods

A total of 294 subjects (48 cleft subjects and 50 healthy controls with both their parents) were selected. Finger and palm prints of all were recorded using the ink method.

Results

Increased frequency of loops and arches and low mean total ridge count was observed in cleft subjects. Increased frequency of loops and arches with decreased frequency of whorls, mean total ridge count, and atd angle of right hand was found in parents of cleft group as compared with the parents of the controls.

Conclusion

Dermatoglyphic patterns have considerable variances. They can be used to study genetic etiology and as an educational tool for genetic counseling.
Three-Dimensional Reconstruction of Large Secondary Alveolar Cleft by Two-Stage Distraction
Authors: Rachmiel Adi , Emodi Omri , Aizenbud Dror
Published: August 2012

Objective

Our aim is to demonstrate a method for reconstruction of a wide alveolar cleft before implant placement.

Patient and Method

An adult patient with a unilateral cleft palate and a wide alveolar and maxillary bone defect underwent transport distraction osteogenesis to medialize the left segment and reduce the alveolar cleft to a minimum. Removal of the transport distraction device was accompanied by autogenous bone grafting to the remaining alveolar defect in the medial cleft, attaining an osseous closure with adequate soft-tissue coverage. Three months later, vertical alveolar distraction of the newly reconstructed bone was performed. Implants were placed after the removal of the distraction device.

Results

Alveolar bone was transported forward 20 mm followed by 15 mm vertical distraction. The large cleft palate defect was reconstructed in three dimensions by the two-stage distraction osteogenesis, and the soft tissues were expanded to achieve functional correction. After removal of the distraction device, dental implants were osteointegrated in the newly reconstructed bone for fixed dental rehabilitation.

Conclusions

The two-stage distraction allowed gradual closure of a large defect three dimensionally. This method can be safely performed not only in patients undergoing initial treatment for large alveolar clefts but also after failed bone grafting.
Diuron Occurrence and Distribution in Soil and Surface and Ground Water Associated with Grass Seed Production
Authors: Field Jennifer A. , Reed Ralph L. , Sawyer Thomas E. , Griffith Steven M. , Wigington P. J.
Published: August 2012

Little is known about the occurrence and distribution of the herbicide diuron [3‐(3,4‐dichlorophenyl)‐1,1‐dimethyl urea] in soil, ground water, and surface water in areas affected by grass‐seed production. A field study was designed to investigate the occurrence and distribution of diuron and its transformation products at a poorly drained field site located along an intermittent tributary of Lake Creek in the southern Willamette Valley of Oregon. The experimental sites consisted of a field under commercial grass seed production with a cultivated riparian zone and a second site that was part of the same grass seed field but with a noncultivated riparian zone. Diuron and its transformation product DCPMU [3‐(3,4‐dichlorophenyl)‐1‐methylurea] were the only significant residues detected in this study. Concentrations of diuron in surface water declined from a maximum of 28 μg/L immediately following application to low levels that persisted as long as flow was present. Diuron and DCPMU concentrations in shallow ground water (15–36 cm below ground surface) were highest (2–13 μg/L) in the zone immediately adjacent (0.5 m) to Lake Creek and indicated the influence of stream water on shallow ground water near the stream. Diuron and DCPMU detected in soil prior to the second season's application indicated the persistence of diuron and DCPMU from the previous year's application. Surface runoff during the rainy season removes only a very small percentage (<1%) of the applied herbicide. In addition, no evidence was obtained for the downward transport of diuron or its transformation products to deep ground water.
Tumor Initiation in Human Malignant Melanoma and Potential Cancer Therapies
Authors: Ma Jie , Frank Markus H.
Published: August 2012

Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment.
Liver Cancer Stem Cells as an Important Target in Liver Cancer Therapies
Authors: Zou Gang-Ming
Published: August 2012

Hepatic cancer is one of most common cause of cancer-related death. Hepato-epithelial cancers are believed to originate from the malignant transformation of liver-resident stem/progenitor cells. Liver cancer stem cells have been characterized recently and the phenotype of liver cancer stem cells has been defined as CD133+ CD44+ cancer cells. Recently, it has been also demonstrated about the relevance of targeting liver cancer stem cells, due to cancer stem cells are related to cancer metastasis. These advances no doubt to bring the new strategy in liver cancer treatment and control in this disease. This review describes the current status and progress about cancer stem cell research in liver and discuss of the implications of these studies in new liver cancer treatment strategies.
Targeting Ovarian Cancer-Initiating Cells
Authors: Murphy Susan K.
Published: August 2012

Evidence supports that a variety of cancers are sparked by the growth of cells that exhibit characteristics of stem cells. Such cancer-initiating cells are capable of populating a tumor with a heterogeneous group of daughter cells while still maintaining the ability to self-renew. Several groups have recently reported the identification of cancer-initiating cells in ovarian cancer, the most lethal gynecologic malignancy. Epithelial ovarian cancer comprises 90% of cancers of the ovary and consists of four major histologic types, each bearing some resemblance to different tissues in the peritoneal cavity. Although epithelial ovarian cancer has traditionally been thought to originate from the single layer of cells surrounding each ovary, new findings suggest that many of these cancers derive from Mullerian epithelium. This raises questions about the origin of ovarian cancer-initiating cells, and if there may be more than one source. Despite the initial effectiveness of primary therapy against advanced stage ovarian cancer, most of these cases recur, months to years following diagnosis. The cause of disease recurrence is unknown, but may involve cancer-initiating cells that survive chemotherapy and enter a period of dormancy while residing in as-yet undefined niches within the body before being triggered to initiate renewed growth. Herein the nature of these cells is explored as well as novel approaches for therapeutic targeting.
Targeting the Acute Myeloid Leukemia Stem Cells
Authors: Krause Alexandre , Fontanari Krause Luciana M. , Rego Eduardo M.
Published: August 2012

The idea that within the bulk of leukemic cells there are immature progenitors which are intrinsically resistant to chemotherapy and able to repopulate the tumor after treatment is not recent. Nevertheless, the term leukemia stem cells (LSCs) has been adopted recently to describe these immature progenitors based on the fact that they share the most relevant features of the normal hematopoetic stem cells (HSCs), i.e. the self-renewal potential and quiescent status. LSCs differ from their normal counterparts and from the more differentiated leukemic cells regarding the default status of pathways regulating apoptosis, cell cycle, telomere maintenance and transport pumps activity. In addition, unique features regarding the interaction of these cells with the microenvironment have been characterized. Therapeutic strategies targeting these unique features are at different stages of development but the reported results are promising. The aim of this review is, by taking acute myeloid leukemia (AML) as a bona fide example, to discuss some of the mechanisms used by the LSCs to survive and the strategies which could be used to eradicate these cells.
Gliomagenesis and the Use of Neural Stem Cells in Brain Tumor Treatment
Authors: Achanta Pragathi , Sedora Roman Neda I. , Quinones-Hinojosa Alfredo
Published: August 2012

The role of neural stem cells (NSCs) in both the physiological and pathological processes in the brain has been refined through recent studies within the neuro-oncological field. Alterations in NSC regulatory mechanisms may be fundamental for the development and progression of malignant gliomas. A subpopulation of cells within the tumor known as brain tumor stem cells (BTSCs) have been shown to share key properties with NSCs. The BTSC hypothesis has significantly contributed to a potential understanding as to why brain tumors hold such dismal prognosis. On the other hand, the normal NSCs possess the capacity to migrate extensively towards the tumor bulk as well as to lingering neoplastic regions of the brain. The tropism of NSCs towards brain tumors may provide an additional tool for the treatment of brain cancer. The creation of potential therapies through the use of NSCs has been studied and includes the delivery of gene products to specific locations of the central nervous system selectively targeting malignant brain tumor cells and maximizing the efficiency of their delivery. Here, the proposed mechanisms of how brain tumors emerge, the molecular pathways interrupted in NSC pathogenesis and the most recent preclinical results in the use of NSCs for glioma treatment are reviewed.
Lung Cancer Stem Cells as a Target for Therapy
Authors: Gorelik Elieser , Lokshin Anna , Levina Vera
Published: August 2012

Despite significant efforts in diagnosing and treating lung cancer, therapeutic resistance remains a major unresolved clinical and scientific problem. Cancer stem cells (CSCs) are thought to be responsible for the failure of current chemotherapy of lung cancer. The concept of CSCs has radically changed the view of cancer therapy. Today a majority of current treatment modalities target the differentiated cancer cells and avoid the drug resistant cancer-initiating stem cells. This review summarizes our understanding of lung CSCs and their role in metastasis formation and growth of non- small-cells lung cancer (NSCLC). High tumorigenic and metastatic properties of lung CSCs are associated with the efficient cytokine network production and with the specific signaling pathways. This review underlines the experimental evidence indicating that the stem cell factor (SCF) and its receptor c-kit (CD117) play an important role in survival and proliferation of lung CSCs. Thus, molecularly targeting key cytokine network axes of such highly tumorigenic and metastatic CSCs must be considered for improving the current anti-cancer strategy efficacy. Standard chemotherapy in combination with specific axis of cytokine network targeting, such as SCF-c-kit, could eliminate both bulk tumor cells and CSCs, and therefore to be truly curative therapies. This review provides a summary of some of the developments in the field of lung CSCs targeting and highlights aspects which could help in the drug discovery process.
Gestational Trophoblastic Neoplasia, an Ancient Disease: New Light and Potential Therapeutic Targets
Authors: Alazzam Mo 'iad , Tidy John , Hancock Barry W. , Powers Hilary J.
Published: August 2012

Gestational trophoblastic neoplasia is a rare malignancy, which can occur after any type of pregnancy. The incidence varies according to the geographical location and ethnic origin. Although most patients with gestational trophoblastic neoplasia are cured by conventional chemotherapy and surgery, some suffer resistant disease and may die. New therapeutic agents are needed to reduce the toxicity associated with conventional chemotherapy and treat those with resistant or refractory disease. Molecular targeted treatment provides an exciting avenue; however, the biology of gestational trophoblastic neoplasia is not well understood. This review briefly summarises recent advances in the understanding of the pathogenesis and molecular biology of this group of diseases and sheds light on molecules that could provide potential therapeutic targets.
Novel Therapeutic Agents Against Cancer Stem Cells of Chronic Myeloid Leukemia
Authors: Chen Yaoyu , Peng Cong , Sullivan Con , Li Dongguang , Li Shaoguang
Published: August 2012

Chronic myeloid leukemia (CML) is induced by the BCR-ABL oncogene, a product of Philadelphia (Ph) chromosome. The BCR-ABL kinase inhibitor imatinib is a standard treatment for Ph+ leukemia, and has been shown to induce a complete hematologic and cytogenetic response in most chronic phrase CML patients. However, imatinib does not cure CML, and one of the reasons is that imatinib does not kill leukemia stem cells (LSCs) in CML both in vitro and in vivo. Recently, several new targets or drugs have been reported to inhibit LSCs in cultured human CD34+ CML cells or in mouse model of BCR-ABL induced CML, including an Alox5 pathway inhibitor, Hsp90 inhibitors, omacetaxine, hedgehog inhibitor and BMS-214662. Specific targeting of LSCs but not normal stem cell is a correct strategy for developing new anti-cancer therapies in the future.
Multiple Myeloma: A Paradigm for Translation of the Cancer Stem Cell Hypothesis
Authors: Agarwal Jasmin Roya , Matsui William
Published: August 2012

Despite recent advances in drug development, multiple myeloma (MM) remains incurable for the majority of patients due to relapse and disease progression. The cancer stem cell (CSC) hypothesis may provide an explanation for these clinical findings. It suggests that the long-term proliferative potential responsible for disease initiation, maintenance, and relapse is contained within specific subpopulations of biologically distinct tumor cells. Data in MM suggest that CSCs represent a rare cell population phenotypically resembling normal memory B cells. Compared to MM plasma cells, MM CSCs also appear to be relatively resistant to a wide variety of standard anti-cancer agents suggesting they may persist following treatment and mediate tumor re-growth and relapse. A unique property CSCs share with their normal counterparts is the potential for self-renewal that likely maintains the malignant clone over time. The development of therapeutic strategies targeting the signaling elements contributing to cancer cell self-renewal has been limited primarily because the cellular processes involved are poorly understood. However, it is common that the signaling pathway components regulating normal stem cell self-renewal are aberrantly activated in human cancers and may serve as potential therapeutic targets. One class of shared regulatory pathways are those active during normal embryonic patterning and organ formation such as Hedgehog (Hh), Notch and Wingless (Wnt), and emerging data suggest that these may play a role in CSCs. Here we review the identification and characterization of MM CSCs, the role of Hh in MM, and issues to be considered during the early clinical testing of CSC targeting agents.
Novel Therapies Against Aggressive and Recurrent Epithelial Cancers by Molecular Targeting Tumor- and Metastasis-Initiating Cells and Their Progenies
Authors: Mimeault Murielle , Batra Surinder K.
Published: August 2012

A growing body of experimental evidence has revealed that the highly tumorigenic cancer stem/progenitor cells endowed with stem cell-like properties might be responsible for initiation and progression of numerous aggressive epithelial cancers into locally invasive, metastatic and incurable disease states. The malignant transformation of tissue-resident adult stem/progenitor cells or their progenies into tumorigenic and migrating cancer stem/progenitor cells and their resistance to current cancer therapies have been associated with their high expression levels of specific oncogenic products and drug resistance-associated molecules. In this regard, we describe the tumorigenic cascades that are frequently activated in cancer stem/progenitor cells versus their differentiated progenies during the early and late stages of the epithelial cancer progression. The emphasis is on the growth factor signaling pathways involved in the malignant behavior of prostate and pancreatic cancer stem/progenitor cells and their progenies. Of clinical interest, the potential molecular therapeutic targets to eradicate the tumor- and metastasis-initiating cells and their progenies and develop new effective combination therapies against locally advanced and metastatic epithelial cancers are also described.
Potential Targets for Improving Radiosensitivity of Breast Tumor-Initiating Cells
Authors: Xu Wei , Debeb Bisrat G. , Lacerd Lara , Woodward Wendy A.
Published: August 2012

Recent studies have suggested that a specific small population of cells termed tumor-initiating cells (TICs) may be intrinsically resistant to therapy including radiation, and may therefore be the primary mediators of recurrence. Numerous targets are being explored using multiple approaches for their involvement in the self-renewal or survival as well as radioresistance of breast TICs. These studies will provide a broad range of compounds to be tested and to develop novel TIC radiosensitizers that will improve clinical outcome and decrease recurrence of cancer after radiation. In this review we will discuss recent efforts to identify and target these cells to selectively radiosensitize them with novel agents, as well as the TIC radiosensitizing potential of current therapies already in clinical use.
Selenium in the Prevention and Treatment of Hepatocellular Carcinoma
Authors: S. Darvesh Altaf , Bishayee Anupam
Published: August 2012

Hepatocellular carcinoma (HCC) happens to be one of the most lethal cancers in the world. Even though most cases occur in the developing world, reported cases in Western Europe as well as North America are on a steep rise. Human HCC etiology includes chronic liver disease, viral hepatitis, alcoholism, iron overload as well as dietary carcinogens such as aflatoxins and nitrosoamines. Surgical resection as well as liver transplants, which are currently used to treat HCC, is mostly ineffective. Consequently, there exists a decisive requirement to explore possible alternative chemopreventive and therapeutic strategies for HCC. Both oxidative stress and inflammatory mechanisms have been implicated in the pathophysiology of HCC. The use of dietary antioxidants and micronutrients has been proposed as an effective means for successful management of human HCC. Trace elements such as vanadium and selenium are involved in several major metabolic pathways as well as antioxidant defense systems. Selenium has been shown to be involved in the prevention of numerous chronic illnesses such as several specific cancers and neurodegenerative diseases. This review examines the potential role of selenium in the prevention and treatment of HCC. The in vivo and in vitro effects of selenium and the mechanisms involved in preclinical models of liver cancer are critically reviewed in this article. The chemopreventive and therapeutic effects of selenium are reviewed especially in relation to its antioxidant property. Future directions and potential challenges involved in the advance of selenium use in the prevention and treatment of liver cancer are also discussed.
Mechanisms of Cytotoxicity of Anticancer Titanocenes
Authors: Olszewski Ulrike , Hamilton Gerhard
Published: August 2012

The organometallic compound titanocene (bis(cyclopentadienyl)titanium(IV) dichloride) showed promising preclinical anticancer activity in generally resistant tumors in vitro and in vivo but failed in clinical trials. A broad range of analogs with modified cyclopentadienyl ligands conferring increased stability and higher cytotoxicity were developed. Titanium was found to accumulate in the nucleus and inhibit DNA replication and transcription. The active species causing irreversible damage and exact mechanisms of action resulting in cell cycle arrest and apoptosis have not been identified to date. Our group investigated changes in global gene expression of NCI-H526 small cell lung cancer cells in response to the novel analog titanocene C (bis-N,N-dimethylamino-2-(N-methylpyrrolyl) methyl cyclopentadienyl titanium (IV)). Differences observed in transcript levels indicated downregulation of DNA unwinding by topoisomerases I and IIα and activation of responses to DNA damage and cellular stress, as well as shutdown of energy metabolism and, finally, apoptosis. Besides direct interaction of Ti2+ with DNA, induction of the MT1 family of metallothionein genes and downregulation of cellular Zn2+ uptake in response to titanocene C pointed to disturbed Zn2+ homeostasis, which triggers cell cycle arrest and apoptosis due to defective transcription factors and metalloenzymes. In particular, histone H4 genes dependent on Zn2+-containing transcription factors H4TF-1/2 were specifically downregulated, and accumulation of defective metalloproteins in the endoplasmatic reticulum seemed to activate unfolded protein response. In conclusion, according to these results, we propose a model of titanocene-induced cytotoxicity, comprising direct DNA damage and perturbation of Zn2+ homeostasis with impairment of the functions of cellular metalloproteome.
Status of Bi- and Multi-Nuclear Platinum Anticancer Drug Development
Authors: Zhang Jinchao , Wang Liwei , Xing Zhiyong , Liu Dandan , Sun Jing , Li Xiaoliu , Zhang Ying
Published: August 2012

Cisplatin has become one of the most commonly used compounds for the treatment of a wide spectrum of human malignancies. Unfortunately, cisplatin has several major drawbacks. Driven by the impressive impact of cisplatin on cancer chemotherapy, great efforts have been made to develop new derivatives with improved pharmacological properties. Among the over 30 platinum agents which have entered clinical trials after the onset of clinical studies with cisplatin in the early 1970s, only carboplatin and oxaliplatin have received worldwide approval so far, nedaplatin, lobaplatin and heptaplatin have gained regionally limited approval. It has become quite evident that mere analogues of cisplatin or carboplatin will not probably offer any substantial clinical advantages over the existing drugs. Therefore, people turned to synthesize non-classical platinum anticancer drugs which were capable of forming a different range of DNA adducts which could display a different spectrum of anticancer activity compared to cisplatin. This review will summarize the structural types and structure-activity rules of non-classical bi- and multi-nuclear platinum anticancer drugs, and discuss their future potential as anticancer agents.
Boron-Containing Compounds as Preventive and Chemotherapeutic Agents for Cancer
Authors: I. Scorei Romulus , Popa Radu
Published: August 2012

In the last few years boron (B) compounds became increasingly frequent in the chemotherapy of some forms of cancer with high malignancy and of inoperable cancers. As more B-based therapy chemicals are developed it is necessary to review the correlation between B and the incidence of different forms of cancer, the biochemical and molecular mechanisms influenced by B and to explore the relevance of B in the chemoprevention of cancer. This minireview analyzes dietary and therapeuptic principles based on the chemistry of B compounds. We summarize studies correlating B-rich diets or B-rich environments with regional risks of specific forms of cancers, and studies about the utilization of natural and synthetic B-containing compounds as anticancer agents. We review mechanisms where B-containing compounds interfere with the physiology and reproduction of cancer cells. Types of cancers most frequently impacted by B-containing compounds include prostate, breast, cervical and lung cancer. Mechanisms involving B activity on cancer cells are based on the inhibition of a variety of enzymatic activities, including serine proteases, NAD-dehydrogenases, mRNA splicing and cell division, but also receptor binding mimicry, and the induction of apoptosis. Boron-enriched diets resulted in significant decrease in the risk for prostate and cervical cancer, and decrease in lung cancer in smoking women. Boron-based compounds show promising effects for the chemotheraphy of specific forms of cancer, but due to specific benefits should also be included in cancer chemopreventive strategies.
Latest Insights into the Anticancer Activity of Gold(III)-Dithiocarbamato Complexes
Authors: Ronconi Luca , Aldinucci Donatella , Ping Dou Q. , Fregona Dolores
Published: August 2012

In this review paper we aim at giving a detailed overview on our research work devoted to the design of gold-based anticancer agents. In particular, during the last decade, we have been developing some gold(III)-dithiocarbamato derivates showing outstanding in vitro and in vivo antitumor properties and reduced, or even no, systemic and renal toxicity, compared to the reference clinically-established anticancer drug cisplatin. Starting from the rationale behind our investigations, we here summarize the results achieved so far, focusing on the latest in-depth mechanistic studies that have recently provided insights into their mechanism of action, thus opening up new prospects for further pharmacological testing and, hopefully, to enter clinical trials.
A Better Platinum-Based Anticancer Drug Yet to Come?
Authors: Olszewski Ulrike , Hamilton Gerhard
Published: August 2012

In attempts to overcome the drawbacks of cisplatin – severe toxicity, drug resistance and poor oral bioavailability – the development of platinum-based drugs has progressed from carboplatin and oxaliplatin to the newest generation of drugs, such as satraplatin, picoplatin and the multinuclear platinum complex BBR3464 (triplatin). Despite encouraging preclinical in vitro and in vivo results, outcomes of clinical trials of these coordination complexes remained below expectations. Biased rationale underlying the drug design along with in vitro and in vivo preclinical tests with inadequate predictive power seem to have eventually resulted in the selection of drug candidates of limited clinical activity. The nature of the active species generated in vivo, uptake, efflux, intracellular trafficking and detailed mechanisms involved in chemoresistance of platinum drugs in vivo are topics that need further investigation to provide clues for the rational formulation of new drugs. Insufficient diffusion in tumor tissues is likely to constitute an important limiting step in the treatment of solid tumors with platinum compounds. Preclinical assays with improved predictive power for the clinical outcome of the compounds should be based on more representative tumor models, such as resistant primary cancer cell lines, spheroids and orthotopic xenograft models, respectively. Finally, use of new pharmaceutical formulations and bifunctional complexes, as well as their selection by decisive preclinical tests, are expected to result in the generation of platinum-based anticancer drugs with the potential to achieve clinical activity even in multidrug-resistant tumors.
Proteomic and Metallomic Strategies for Understanding the Mode of Action of Anticancer Metallodrugs
Authors: Gabbiani Chiara , Magherini Francesca , Modesti Alessandra , Messori Luigi
Published: August 2012

Since the discovery of cisplatin and its introduction in the clinics, metal compounds have been intensely investigated in view of their possible application in cancer therapy. In this frame, a deeper understanding of their mode of action, still rather obscure, might turn crucial for the design and the obtainment of new and better anticancer agents. Due to the extreme complexity of the biological systems, it is now widely accepted that innovative and information-rich methods are absolutely needed to afford such a goal. Recently, both proteomic and metallomic strategies were successfully implemented for the elucidation of specific mechanistic features of anticancer metallodrugs within an innovative “Systems Biology” perspective. Particular attention was paid to the following issues: i) proteomic studies of the molecular basis of platinum resistance; ii) proteomic analysis of cellular responses to cytotoxic metallodrugs; iii) metallomic studies of the transformation and fate of metallodrugs in cellular systems. Notably, those pioneering studies, that are reviewed here, allowed a significant progress in the understanding of the molecular mechanisms of metal based drugs at the cellular level. A further extension of those studies and a closer integration of proteomic and metallomic strategies and technologies might realistically lead to rapid and significant advancements in the mechanistic knowledge of anticancer metallodrugs.
Obstetric Nephrology
Authors: Odutayo Ayodele , Hladunewich Michelle
Published: August 2012

Glomerular hyperfiltration, altered tubular function, and shifts in electrolyte-fluid balance are among the hallmark renal physiologic changes that characterize a healthy pregnancy. These adjustments are not only critical to maternal and fetal well being, but also provide the clinical context for identifying gestational aberrations in renal function and electrolyte composition. Systemic vasodilation characterizes early gestation and produces increments in renal plasma flow and GFR, the latter of which is maintained into the postpartum period. In addition, renal tubular changes allow for the accumulation of nutrients and electrolytes necessary for fetal growth such that wasting of proteins, glucose, and amino acids in urine is limited in pregnancy and total body stores of electrolytes increase throughout gestation. Substantial insight into the mechanisms underlying these complex adjustments can be gleaned from the available animal and human literature, but our understanding in many areas remains incomplete. This article reviews the available literature on renal adaptation to normal pregnancy, including renal function, tubular function, and electrolyte-fluid balance, along with the clinical ramifications of these adjustments, the limitations of the existing literature, and suggestions for future studies.
CKD, Plasma Lipids, and Common Carotid Intima-Media Thickness
Authors: Lamprea-Montealegre Julio A. , Astor Brad C. , McClelland Robin L. , de Boer Ian H. , Burke Gregory L. , Sibley Christopher T. , O’Leary Daniel , Sharrett A. Richey , Szklo Moyses
Published: August 2012

Background and objectives

Altered levels of atherogenic lipoproteins have been shown to be common in mild kidney dysfunction. This study sought to determine the associations between plasma lipids (including LDL particle distribution) and subclinical atherosclerosis measured by the common carotid intima-media thickness (IMT) across levels of estimated GFR (eGFR) and to assess whether inflammation modifies these associations.

Design, setting, participants, & measurements

Cross-sectional analyses of 6572 participants in the Multi-Ethnic Study of Atherosclerosis enrolled from 2000 to 2002 were performed.

Results

CKD, defined as eGFR <60 ml/min per 1.73 m2, was present in 853 individuals (13.0%). Associations of total cholesterol and LDL cholesterol (LDL-C) with IMT were J shaped, particularly among participants with CKD (P value for interaction, P=0.01). HDL cholesterol (HDL-C) and small-dense LDL-C were consistently and linearly associated with IMT across levels of eGFR. The results showed differences in IMT of −21.41 (95% confidence interval, −41.00, −1.57) in eGFR ≥60 and −58.49 (−126.61, 9.63) in eGFR <60 per unit difference in log-transformed HDL-C, and 4.83 (3.16, 6.50) in eGFR ≥60 and 7.48 (1.45, 13.50) in eGFR <60 per 100 nmol/L difference in small-dense LDL. Among participants with CKD, inflammation significantly modified the associations of total cholesterol and LDL-C with IMT (P values for interaction, P<0.01 and P<0.001, respectively).

Conclusions

Compared with total cholesterol and LDL-C, abnormalities in HDL-C and small-dense LDL-C are more strongly and consistently associated with subclinical atherosclerosis in CKD. Inflammation modifies the association between total cholesterol and LDL-C with IMT.
Onco-Nephrology
Authors: Rosner Mitchell H. , Dalkin Alan C.
Published: August 2012

Hypercalcemia complicates the course of 10%–30% of all patients with malignancies and can be a sign of very poor prognosis and advanced malignancy. Prompt recognition of the nonspecific signs and symptoms of hypercalcemia and institution of therapy can be lifesaving, affording the opportunity to address the underlying etiology. The mechanisms of malignancy-associated hypercalcemia generally fall into three categories: humoral hypercalcemia due to secreted factors (such as parathyroid-related hormone), local osteolysis due to tumor invasion of bone, and absorptive hypercalcemia due to excess vitamin D produced by malignancies. The mainstays of therapy for hypercalcemia are aggressive intravenous volume expansion with saline, bisphosphonate therapy, and perhaps loop diuretics. Adjunctive therapy may include calcitonin and corticosteroids. In refractory cases, gallium nitrate and perhaps denosumab are alternatives. In patients presenting with severe AKI, hemodialysis with a low-calcium bath can be effective. In most cases, therapy normalizes calcium levels and allows for palliation or curative therapy of the malignancy.
Onco-Nephrology
Authors: Perazella Mark A.
Published: August 2012

Despite dramatic improvements in patient survival and drug tolerability, nephrotoxicity remains an important complication of chemotherapy. Adverse renal effects occur because of innate drug toxicity and a number of patient- and drug-related factors. To provide cutting edge care for these patients, nephrologists and oncologists must be familiar with the nephrotoxicity of these drugs, particularly their associated clinical and laboratory manifestations. Rapid diagnosis, targeted treatment, and supportive care are critical to improving care for these patients. Unfortunately, some patients who develop nephrotoxicity will be left with long-term complications such as chronic tubulopathies and CKD. Onco-Nephrology is a new area that is rapidly expanding and requires a close working relationship between oncologists and nephrologists.
Onco-Nephrology
Authors: Lam Albert Q. , Humphreys Benjamin D.
Published: August 2012

AKI is common in patients with cancer, and it causes interruptions in therapy and increased hospital length of stay, cost, and mortality. Although cancer patients are susceptible to all of the usual causes of AKI in patients without cancer, there are a number of AKI syndromes that occur more frequently or are unique to this patient population. AKI also confers substantially increased risk of short-term death, and the ability to reverse AKI portends a better outcome in some cancers, such as multiple myeloma. Several trends in oncology, including increased survival, better supportive care, older patients who have received multiple chemotherapy regimens, and new therapeutic options, are driving an increase in the numbers of cancer patients who develop AKI. As a result, nephrologists should be increasingly familiar with the diagnosis, management, and treatment of AKI in this setting. Here, we summarize recent data on epidemiology of AKI in cancer patients, describe the most common AKI syndromes in this population, and highlight emerging areas in the growing field of onconephrology.
Onco-Nephrology
Authors: Wilson F. Perry , Berns Jeffrey S.
Published: August 2012

Tumor lysis syndrome (TLS) describes the clinical and laboratory sequelae that result from the rapid release of intracellular contents of dying cancer cells. It is characterized by the release of potassium, phosphorous, and nucleic acids from cancer cells into the blood stream, with the potential to cause hyperkalemia; hyperphosphatemia and secondary hypocalcemia; hyperuricemia; AKI; and, should usual homeostatic mechanisms fail, death. TLS most commonly follows treatment of hematologic malignancies, such as acute lymphocytic or lymphoblastic leukemia, acute myeloid leukemia, and Burkitt lymphoma, but also occurs after treatment of other bulky or rapidly growing tumors, particularly if the patient is highly sensitive to the effects of cytotoxic chemotherapy. Prevention and treatment depend on prompt recognition of patients at risk, volume repletion, allopurinol, rasburicase (a novel recombinant urate oxidase), and, when indicated, dialysis.
Lupus Nephritis
Authors: Rovin Brad H. , Parikh Samir V. , Hebert Lee A. , Chan Tak Mao , Mok Chi Chiu , Ginzler Ellen M. , Hooi Lai Seong , Brunetta Paul , Maciuca Romeo , Solomons Neil
Published: August 2012

Severe lupus nephritis is an aggressive disease that requires an aggressive approach to treatment. Recent randomized clinical trials showed that mycophenolate mofetil compared favorably with cyclophosphamide (traditional approach) for remission induction. Consequently, mycophenolate mofetil is now commonly recommended as first-line therapy. Nevertheless, the role of mycophenolate mofetil in treating severe lupus nephritis is unclear, because such patients were excluded from these trials. With this limitation as background, this work addresses the question of mycophenolate mofetil for induction therapy for severe lupus nephritis. We performed a systematic review of the outcomes of treating severe lupus nephritis with mycophenolate mofetil or cyclophosphamide. Because no studies directly addressed this question, these data were extracted from the published literature or obtained by personal communications from investigators. There is no universally accepted definition, and therefore, severe lupus nephritis was arbitrarily defined by renal histology, resistance to therapy, or level of kidney function at presentation. For each trial analyzed, we determined the partial and complete remission rates. Long-term outcomes were compared when available. The pooled results suggest that mycophenolate mofetil and cyclophosphamide are equally effective in inducing remission of severe lupus nephritis. However, relapse rates and risk of developing ESRD were higher for mycophenolate mofetil compared with cyclophosphamide. In conclusion, in the short term, mycophenolate mofetil and cyclophosphamide are about equal in inducing remission. However, long-term outcomes suggest better preservation of kidney function and fewer relapses with cyclophosphamide therapy. Therefore, mycophenolate mofetil should not yet be considered the induction drug of choice for severe lupus nephritis.
Obstetric Nephrology
Authors: Stanhope Todd J. , White Wendy M. , Moder Kevin G. , Smyth Andrew , Garovic Vesna D.
Published: August 2012

SLE is a multi-organ autoimmune disease that affects women of childbearing age. Renal involvement in the form of either active lupus nephritis (LN) at the time of conception, or a LN new onset or flare during pregnancy increases the risks of preterm delivery, pre-eclampsia, maternal mortality, fetal/neonatal demise, and intrauterine growth restriction. Consequently, current recommendations advise that the affected woman achieve a stable remission of her renal disease for at least 6 months before conception. Hormonal and immune system changes in pregnancy may affect disease activity and progression, and published evidence suggests that there is an increased risk for a LN flare during pregnancy. The major goal of immunosuppressive therapy in pregnancy is control of disease activity with medications that are relatively safe for a growing fetus. Therefore, the use of mycophenolate mofetil, due to increasing evidence supporting its teratogenicity, is contraindicated during pregnancy. Worsening proteinuria, which commonly occurs in proteinuric renal diseases toward the end of pregnancy, should be differentiated from a LN flare and/or pre-eclampsia, a pregnancy-specific condition clinically characterized by hypertension and proteinuria. These considerations present challenges that underscore the importance of a multidisciplinary team approach when caring for these patients, including a nephrologist, rheumatologist, and obstetrician who have experience with these pregnancy-related complications. This review discusses the pathogenesis, maternal and fetal risks, and management pertinent to SLE patients with new onset or a history of LN predating pregnancy.
Obstetric Nephrology
Authors: Fakhouri Fadi , Vercel Caroline , Frémeaux-Bacchi Véronique
Published: August 2012

AKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab).
Subcultural Differences in Taiwanese and Burmese Chinese Business Negotiation Styles
Authors: Chang Lieh Ching
Published: August 2012

The subcultural differences in business negotiation styles between Taiwanese businesspeople and a small group of Burmese Chinese who have businesses in Taiwan were analyzed. Negotiating styles of collaboration, compromise, accommodation, competition, and withdrawal were examined, focusing
on influential factors such as subculture and relationship and task-oriented conflicts. Results showed that the main difference between the 2 groups was that whereas Burmese Chinese tend to shun conflict and may even submit to their opponent to prevent a conflict from escalating, Taiwanese
are less likely to employ an accommodation strategy. The conclusion was reached that in a task-oriented or relationship conflict, in a business situation Taiwanese and Burmese Chinese people differ significantly in their use of collaboration, accommodation, and withdrawal as negotiation styles.