MedWorm: Cancer Therapy

For Personalizing Cancer Therapy, Metabolic Profiles Are Essential

Health News from Medical News Today — Wed, 08 Feb 2012 09:00:00 +0100

One way to tackle a tumor is to take aim at the metabolic reactions that fuel their growth. But a report in the February Cell Metabolism, a Cell Press Publication, shows that one metabolism-targeted cancer therapy will not fit all. That means that metabolic profiling will be essential for defining each cancer and choosing the best treatment accordingly, the researchers say. The evidence comes from studies in mice showing that tumors' metabolic profiles vary based on the genes underlying a particular cancer and on the tissue of origin... (Source: Health News from Medical News Today)

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Personalizing Cancer Therapy

Medical Headlines From Ivanhoe.com — Wed, 08 Feb 2012 05:00:00 +0100

(Ivanhoe Newswire)-- When fighting tumors it is essential doctors target the metabolic reactions that fuel their growth. (Source: Medical Headlines From Ivanhoe.com)

Immunotherapeutic Potential of Anti-Human Endogenous Retrovirus-K Envelope Protein Antibodies in Targeting Breast Tumors

JNCI — Tue, 07 Feb 2012 05:00:00 +0100

Conclusion Monoclonal antibodies against HERV-K env protein show potential as novel immunotherapeutic agents for breast cancer therapy. (Source: JNCI)

Metabolic profiles essential for personalizing cancer therapy

EurekAlert! - Cancer — Tue, 07 Feb 2012 05:00:00 +0100

(Cell Press) One way to tackle a tumor is to take aim at the metabolic reactions that fuel their growth. But a report in the February Cell Metabolism, a Cell Press Publication, shows that one metabolism-targeted cancer therapy will not fit all. That means that metabolic profiling will be essential for defining each cancer and choosing the best treatment accordingly, the researchers say. (Source: EurekAlert! - Cancer)

Remarkable inhibition of mTOR signaling by the combination of rapamycin and 1,4‐phenylenebis(methylene)selenocyanate in human prostate cancer cells

International Journal of Cancer — Sun, 05 Feb 2012 13:03:43 +0100

AbstractPreclinical studies and clinical analyses have implicated the mammalian target of rapamycin (mTOR) pathway in the progression of prostate cancer, suggesting mTOR as a potential target for new therapies. mTOR, a serine/threonine kinase, belongs to two distinct signaling complexes: mTORC1 and mTORC2. We previously showed that the synthetic organoselenium compound, p‐XSC, effectively inhibits viability and critical signaling molecules (e.g., androgen receptor, Akt) in androgen responsive (AR) and androgen independent (AI) human prostate cancer cells. Based on its inhibition of Akt, we hypothesized that p‐XSC modulates mTORC2, an upstream regulator of the kinase. We further hypothesized that combining p‐XSC with rapamycin, an mTORC1 inhibitor, would be an effective combinatory st...

New radiopharmaceutical to be trialed as prostate cancer therapy

Health Imaging News — Fri, 03 Feb 2012 13:33:29 +0100

The radiopharmaceutical, I-131-MIP-1466, which is designed to deliver a therapeutic dose of radiation to metastatic prostate cancer, will enter a clinical trial to evaluate its efficacy and benefits for patients. (Source: Health Imaging News)

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UA Awarded National Cancer Research Grant

Health — Fri, 03 Feb 2012 07:00:00 +0100

The UA and the Translational Genomics Research Institute have received a three-year, $600,000 grant to study targeted cancer therapies. The grant will fund the Center for Targeted Cancer Therapies, created in 2002 to discover new therapies to treat pancreatic cancer. (Source: Health)

PI3K‐independent AKT activation in cancers: A treasure trove for novel therapeutics

Journal of Cellular Physiology — Fri, 03 Feb 2012 05:00:00 +0100

AbstractAKT/PKB serine threonine kinase, a critical signaling molecule promoting cell growth and survival pathways, is frequently dysregulated in many cancers. Although phosphatidylinositol‐3‐OH kinase (PI3K), a lipid kinase, is well characterized as a major regulator of AKT activation in response to a variety of ligands, recent studies highlight a diverse group of tyrosine (Ack1/TNK2, Src, PTK6) and serine/threonine (TBK1, IKBKE, DNAPKcs) kinases that activate AKT directly to promote its pro‐proliferative signaling functions. While some of these alternate AKT activating kinases respond to growth factors, others respond to inflammatory and genotoxic stimuli. A common theme emerging from these studies is that aberrant or hyperactivation of these alternate kinases is often associated w...

Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials

European Radiology — Thu, 02 Feb 2012 18:12:23 +0100

Abstract Imaging is key in the accurate monitoring of response to cancer therapies targeting tumour vascularity to inhibit its growth and dissemination. Dynamic contrast enhanced ultrasound (DCE ultrasound) is a quantitative method with the advantage of being non-invasive, widely available, portable, cost effective, highly sensitive and reproducible using agents that are truly intravascular. Under the auspices of the initiative of the Experimental Cancer Medicine Centre Imaging Network, bringing together experts from the UK, Europe and North America for a 2-day workshop in May 2010, this consensus paper aims to provide guidance on the use of DCE ultrasound in the measurement of tumour vascular support in clinical trials. Key Points • DCE ultrasound can q...

Depression, fatigue, and health-related quality of life in head and neck cancer patients: a prospective pilot study

Supportive Care in Cancer — Thu, 02 Feb 2012 18:11:21 +0100

Conclusions Depression and fatigue symptoms increased during radiotherapy treatment, while QoL levels decreased. This demonstrates that these symptoms are strongly correlated and that their presence negatively influenced QoL. At the start of treatment, nurses need to advise patients and plan care, offering interventions to decrease these symptoms and improve QoL. Content Type Journal ArticleCategory Original ArticlePages 1-7DOI 10.1007/s00520-012-1390-2Authors Namie Okino Sawada, College of Nursing, University of Sao Paulo, Av. Bandeirantes 3900, Monte Alegre, CEP 14040902 Ribeirão Preto, SP, BrazilJuliana Maria de Paula, College of Nursing, University of Sao Paulo, Av. Bandeirantes 3900, Monte Alegre, CEP 14040902 Ribeirão Preto, SP, BrazilHelena Megumi Sonobe, C...

Pharmaceutical care for patients with breast and ovarian cancer

Supportive Care in Cancer — Thu, 02 Feb 2012 06:54:27 +0100

Conclusions Patients with breast and ovarian cancer seem to benefit from pharmaceutical care, as suggested by improved patient-reported outcomes such as emetic episodes, quality of life, and patient satisfaction after implementation. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s00520-012-1385-zAuthors Andrea Liekweg, Institute of Pharmacy, Department of Clinical Pharmacy, University of Bonn, An der Immenburg 4, 53121 Bonn, GermanyMartina Westfeld, Institute of Pharmacy, Department of Clinical Pharmacy, University of Bonn, An der Immenburg 4, 53121 Bonn, GermanyMichael Braun, Center for Integrated Oncology (CIO), Department of Obstetrics and Gynaecology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, GermanyOliver Zivanovic, Cente...

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Tocotrienol as a potential anticancer agent

Carcinogenesis — Thu, 02 Feb 2012 05:00:00 +0100

Vitamin E is composed of two structurally similar compounds: tocopherols (TPs) and tocotrienols (T3). Despite being overshadowed by TP over the past few decades, T3 is now considered to be a promising anticancer agent due to its potent effects against a wide range of cancers. A growing body of evidence suggests that in addition to its antioxidative and pro-apoptotic functions, T3 possesses a number of anticancer properties that make it superior to TP. These include the inhibition of epithelial-to-mesenchymal transitions, the suppression of vascular endothelial growth factor tumor angiogenic pathway and the induction of antitumor immunity. More recently, T3, but not TP, has been shown to have chemosensitization and anti-cancer stem cell effects, further demonstrating the potential of T3 as ...

Orphan receptor TR3 participates in cisplatin-induced apoptosis via Chk2 phosphorylation to repress intestinal tumorigenesis

Carcinogenesis — Thu, 02 Feb 2012 05:00:00 +0100

Cisplatin is a widely used antitumor agent that induces aggressive cancer cell death via triggering cellular proteins involved in apoptosis. Here, we demonstrate that cisplatin effectively induces orphan nuclear receptor TR3 phosphorylation by activating Chk2 kinase activity and promoting cross talk between these two proteins, thereby contributing to the repression of intestinal tumorigenesis via apoptosis. Mechanistic analysis has demonstrated that Chk2-induced phosphorylation enables TR3 to bind to its response elements on the promoters of the BRE and RNF-7 genes, leading to the negative regulation of these two anti-apoptotic genes. Furthermore, the induction of apoptosis by cisplatin is mediated by TR3, and knockdown of TR3 reduces cisplatin-induced apoptosis in colon cancer cells by 27...

EBRT More Costly, Toxic Than Other Prostate Cancer TherapiesEBRT More Costly, Toxic Than Other Prostate Cancer Therapies

Medscape Today Headlines — Wed, 01 Feb 2012 18:48:37 +0100

External-beam radiation therapy (EBRT) for prostate cancer is more costly and more toxic than either prostatectomy or brachytherapy. Medscape Medical News (Source: Medscape Today Headlines)

Against Lung Cancer Cells: To Be, or Not to Be, That Is the Problem

Research Letters in Nanotechnology — Wed, 01 Feb 2012 11:48:01 +0100

Tobacco smoke and radioactive radon gas impose a high risk for lung cancer. The radon-derived ionizing radiation and some components of cigarette smoke induce oxidative stress by generating reactive oxygen species (ROS). Respiratory lung cells are subject to the ROS that causes DNA breaks, which subsequently bring about DNA mutagenesis and are intimately linked with carcinogenesis. The damaged cells by oxidative stress are often destroyed through the active apoptotic pathway. However, the ROS also perform critical signaling functions in stress responses, cell survival, and cell proliferation. Some molecules enhance radiation-induced tumor cell killing via the reduction in DNA repair levels. Hence the DNA repair levels may be a novel therapeutic modality in overcoming drug resistance in lun...

Preclinical Study Identifies New Target For Cancer Therapy

Health News from Medical News Today — Wed, 01 Feb 2012 09:00:00 +0100

Scientists from the Ludwig Institute for Cancer Research (LICR) in Brussels identified a new target for cancer therapy, an enzyme which prevents the immune system from recognizing and destroying certain types of tumors. Called tryptophan 2,3-dioxygenase or TDO, the enzyme works by depriving immune cells of tryptophan, an amino acid essential to their activity. TDO is produced by a significant number of human tumors. Scientists also show that blocking TDO activity with a novel TDO inhibitor promotes tumor rejection in mice... (Source: Health News from Medical News Today)

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UCSB Researchers Discover The Processes Leading To Acute Myeloid Leukemia

Health News from Medical News Today — Wed, 01 Feb 2012 08:00:00 +0100

Researchers at UC Santa Barbara have discovered a molecular pathway that may explain how a particularly deadly form of cancer develops. The discovery may lead to new cancer therapies that reprogram cells instead of killing them. The findings are published in a recent paper in the Journal of Biological Chemistry. The UCSB research team described how a certain mutation in DNA disrupts cellular function in patients with acute myeloid leukemia (AML)... (Source: Health News from Medical News Today)

[Comment] Prostate cancer therapy: finding the right balance

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

More than 30 years ago Willet Whitmore, one of the pioneers in urological oncology, asked the question: “If cure is necessary, is it possible, and if cure is possible, is it necessary?” Such questioning can be applied to the use of androgen suppression therapy. Androgen suppression is an extremely powerful treatment that can help control cancers that recur after primary therapy or are regarded as high risk at the time of presentation. Although clinicians can be proud of the successes obtained with such suppression, many patients who do extremely well might have been overtreated. (Source: The Lancet Oncology)

Blood oxygen level dependent angiography (BOLDangio) and its potential applications in cancer research

NMR in Biomedicine — Wed, 01 Feb 2012 05:00:00 +0100

In this study, the BOLD effect is investigated under different levels of oxygen inhalation for the development of a novel angiographic MRI technique, blood oxygen level dependent angiography (BOLDangio). Under short‐term (<10 min) generalized hypoxia induced by inhalation of 8% oxygen, we measure BOLD contrast as high as 25% from vessels at 9.4T using a simple gradient echo (GRE) pulse sequence. This produces high‐resolution 2D and 3D maps of normal and tumour brain vasculature in less than 10 minutes. Additionally, this technique reliably detects metastatic tumours and tumour‐induced intracranial hemorrhage. BOLDangio provides a sensitive research tool for MRI of vasculature under normal and pathological conditions. Thus, it may be applied as a simple monitoring technique for mea...

Role of Fear of Movement in Cancer Survivors Participating in a Rehabilitation Program: A Longitudinal Cohort Study

Archives of Physical Medicine and Rehabilitation — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: Fear of movement is associated with the perceived global health status of cancer survivors. Fear of movement decreases after rehabilitation with graded activity in high scorers on baseline fear of movement. (Source: Archives of Physical Medicine and Rehabilitation)

An emerging toolkit for targeted cancer therapies [COMMENTARY]

Genome Research — Wed, 01 Feb 2012 05:00:00 +0100

(Source: Genome Research)

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Assessing health‐related quality of life of Chinese‐American breast cancer survivors: a measurement validation study

Psycho-Oncology — Wed, 01 Feb 2012 05:00:00 +0100

ConclusionsOur data demonstrated good internal consistency and construct validity of the measures. The psychometric findings demonstrate the utility of the FACT‐G and the SF‐12 to assess HRQOL among Chinese‐American BCS. Copyright © 2012 John Wiley & Sons, Ltd. (Source: Psycho-Oncology)

Management of cardiac toxicity in patients receiving vascular endothelial growth factor signaling pathway inhibitors

American Heart Journal — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: The panel recommends that physicians (1) conduct and document a formal risk assessment for existing cardiovascular disease and potential cardiovascular complications before VSP inhibitor treatment recognizing that preexisting hypertension and cardiovascular disease are common in patients with cancer, (2) actively monitor for blood pressure elevations and cardiac toxicity with more frequent assessments during the first treatment cycle, and (3) aggressively manage blood pressure elevations and early symptoms and signs of cardiac toxicity to prevent clinically limiting complications of VSP inhibitor therapy. (Source: American Heart Journal)

Estimation of tamoxifen metabolite concentrations in the blood of breast cancer patients through CYP2D6 genotype activity score

Breast Cancer Research and Treatment — Tue, 31 Jan 2012 16:48:05 +0100

Abstract Tamoxifen, a prodrug used for adjuvant breast cancer therapy, requires conversion to the active metabolite endoxifen through CYP 2D6. We aimed to construct an algorithm to predict endoxifen concentrations based on a patient’s CYP 2D6 genotype, demographic factors, and co-medication use. Eighty-eight women enrolled in the UCSF TamGen II study and 81 women enrolled in a prospective study at Dana-Farber Cancer Institute were included in this analysis. All the women had been on tamoxifen for at least 3 months before blood collection. Demographic information included the patient’s age, race/ethnicity, body mass index (where available), and self-reported and measured medications and herbals that affect 2D6 activity. DNA was extracted and genotyped for 2D6 (Ampli...

Immunological Mechanisms Of Oncolytic Adenoviral Therapy

Health News from Medical News Today — Tue, 31 Jan 2012 08:00:00 +0100

Cancer is one of the most common causes of death in humans. The conventional cancer therapies include surgery, radiotherapy, chemotherapy, and targeting therapies, which are intended to directly destroy and eliminate tumor cells. These treatments often fail, resulting in tumor metastasis and recurrence. Therefore, there is a critical need for novel cancer therapies. In recent years, an increasing number of studies have revealed that immune responses play a critical role in conventional cancer therapies... (Source: Health News from Medical News Today)

New target for cancer therapy identified, preclinical study shows

EurekAlert! - Medicine and Health — Tue, 31 Jan 2012 05:00:00 +0100

(Ludwig Institute for Cancer Research) Scientists from the Ludwig Institute for Cancer Research in Brussels identified a new target for cancer therapy, an enzyme which prevents the immune system from recognizing and destroying certain types of tumors. Called tryptophan 2,3-dioxygenase or TDO, the enzyme works by depriving immune cells of tryptophan, an amino acid essential to their activity. TDO is produced by a significant number of human tumors. (Source: EurekAlert! - Medicine and Health)

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National Foundation for Cancer Research funds critical TGen-UA cancer research

EurekAlert! - Medicine and Health — Tue, 31 Jan 2012 05:00:00 +0100

(The Translational Genomics Research Institute) The Translational Genomics Research Institute and the University of Arizona have received a three-year, $600,000 grant to study targeted cancer therapies from the National Foundation for Cancer Research. (Source: EurekAlert! - Medicine and Health)

A Pharmacologic Inhibitor of the Protease Taspase1 Effectively Inhibits Breast and Brain Tumor Growth

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

In this study, we developed and evaluated small molecule inhibitors of Taspase1 as a new candidate class of therapeutic modalities. Genetic deletion of Taspase1 in the mouse produced no overt deficiencies, suggesting the possibility of a wide therapeutic index for use of Taspase1 inhibitors in cancers. We defined the peptidyl motifs recognized by Taspase1 and conducted a cell-based dual-fluorescent proteolytic screen of the National Cancer Institute diversity library to identify Taspase1 inhibitors (TASPIN). On the basis of secondary and tertiary screens the 4-[(4-arsonophenyl)methyl]phenyl] arsonic acid NSC48300 was determined to be the most specific active compound. Structure–activity relationship studies indicated a crucial role for the arsenic acid moiety in mediating Taspase1 inhibi...

Monofunctional Platinum-DNA Adducts Are Strong Inhibitors of Transcription and Substrates for Nucleotide Excision Repair in Live Mammalian Cells

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

In this study, we incorporated pyriplatin globally or site specifically into luciferase reporter vectors to examine its transcription inhibition profiles in live mammalian cells. Monofunctional pyriplatin reacted with plasmid DNA as efficiently as bifunctional cisplatin and inhibited transcription as strongly as cisplatin in various mammalian cells. Using repair-defective nucleotide excision repair (NER)-, mismatch repair-, and single-strand break repair–deficient cells, we show that NER is mainly responsible for removal of pyriplatin–DNA adducts. These findings reveal that the mechanism by which pyriplatin generates its antitumor activity is very similar to that of cisplatin, despite the chemically different nature of their DNA adducts, further supporting a role for monofunctional pla...

Using targeted transgenic reporter mice to study promoter-specific p53 transcriptional activity [Medical Sciences]

Proceedings of the National Academy of Sciences — Tue, 31 Jan 2012 05:00:00 +0100

The p53 transcription factor modulates gene expression programs that induce cell cycle arrest, senescence, or apoptosis, thereby preventing tumorigenesis. However, the mechanisms by which these fates are selected are unclear. Our objective is to understand p53 target gene selection and, thus, enable its optimal manipulation for cancer therapy. We have generated targeted transgenic reporter mice in which EGFP expression is driven by p53 transcriptional activity at a response element from either the p21 or Puma promoter, which induces cell cycle arrest/senescence and apoptosis, respectively. We demonstrate that we could monitor p53 activity in vitro and in vivo and detect variations in p53 activity depending on the response element, tissue type, and stimulus, thereby validating our reporter ...

Sensor-based cell and tissue screening for personalized cancer chemotherapy

Medical and Biological Engineering and Computing — Mon, 30 Jan 2012 16:06:57 +0100

Abstract Personalized tumor chemotherapy depends on reliable assay methods, either based on molecular “predictive biomarkers” or on a direct, functional ex vivo assessment of cellular chemosensitivity. As a member of the latter category, a novel high-content platform is described monitoring human mamma carcinoma explants in real time and label-free before, during and after an ex vivo modeled chemotherapy. Tissue explants are sliced with a vibratome and laid into the microreaction chambers of a 24-well sensor test plate. Within these ≈23 μl volume chambers, sensors for pH and dissolved oxygen record rates of cellular oxygen uptake and extracellular acidification. Robot-controlled fluid system and incubation are parts of the tissue culture maintenance system whil...

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Processes leading to acute myeloid leukemia discovered

ScienceDaily Headlines — Mon, 30 Jan 2012 14:43:43 +0100

Researchers have discovered a molecular pathway that may explain how a particularly deadly form of cancer develops. The discovery may lead to new cancer therapies that reprogram cells instead of killing them. (Source: ScienceDaily Headlines)

CD4 Levels Predict Response to Laryngeal Cancer TherapyCD4 Levels Predict Response to Laryngeal Cancer Therapy

Medscape Today Headlines — Mon, 30 Jan 2012 13:43:01 +0100

Laryngeal cancer patients with increased CD4 levels showed better survival rates and response to induction chemotherapy. Medscape Medical News (Source: Medscape Today Headlines)

Glucocorticoid regulation of a novel HPV E6‐p53‐miR‐145 pathway modulates invasion and therapy resistance of cervical cancer cells

The Journal of Pathology — Mon, 30 Jan 2012 06:38:06 +0100

AbstractGlucocorticoids are stress‐responsive neuroendocrine mediators and play an important role in malignant progression, especially in solid tumors. We demonstrate a novel mechanism by which glucocorticoids modulate p53‐dependent miR‐145 expression in HPV positive cervical cancer cells through induction of E6 proteins. We found that expression of miR‐145 was reduced in cervical cancer tissues. Cortisol induced HPV E6 expression and suppressed p53 and miR‐145 in cervical cancer cells. MiR‐145 expression in cervical cancer cells was wild‐type p53‐dependent, and cortisol‐induced downregulation of miR‐145 expression prevented chemotherapy‐induced apoptosis whereas overexpression of miR‐145 enhanced sensitivity to mitomycin and reversed the chemoresistance induced by ...

UCSB researchers discover the processes leading to acute myeloid leukemia

EurekAlert! - Medicine and Health — Mon, 30 Jan 2012 05:00:00 +0100

(University of California - Santa Barbara) Researchers at UC Santa Barbara have discovered a molecular pathway that may explain how a particularly deadly form of cancer develops. The discovery may lead to new cancer therapies that reprogram cells instead of killing them. The findings are published in a recent paper in the Journal of Biological Chemistry. (Source: EurekAlert! - Medicine and Health)

Mesoporous Silica Nanoparticles in Targeted Cancer TherapyMesoporous Silica Nanoparticles in Targeted Cancer Therapy

Medscape Today Headlines — Mon, 30 Jan 2012 04:00:00 +0100

This report looks at the therapeutic efficacy and safety of mesoporous silica nanoparticles, inorganic particulates under investigation as a drug delivery mechanism for targeted cancer therapy. Nanomedicine (Source: Medscape Today Headlines)

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Atorvastatin delays progression of pancreatic lesions to carcinoma by regulating PI3/AKT signaling in p48Cre/+.LSL‐KrasG12D/+ mice

International Journal of Cancer — Sun, 29 Jan 2012 13:05:18 +0100

AbstractPancreatic cancer is the one of most common causes of cancer deaths and has the worst prognosis. Clinical observational studies suggest that statins may reduce the risk of pancreatic cancer. The chemopreventive efficacy of the statin atorvastatin (Lipitor®) and the role of the phosphatidyl‐inositol 3‐kinase(PI3/AKT) signaling pathway were evaluated for the progression of pancreatic intraepithelial neoplasms (PanINs) to pancreatic ductal adenocarcinoma (PDAC) in conditional p48Cre/+‐LSL‐KrasG12D/+ transgenic mice. Six‐week old male p48Cre/+‐LSL‐KrasG12D/+ (20/group) mice were fed AIN‐76A diets containing 0, 200, and 400 ppm atorvastatin for 35 weeks. At termination, pancreata were evaluated histopathologically for PanINs and PDAC, and for various PI3/AKT signaling m...

ENDOGLIN/CD105 is expressed in KIT positive cells in the gut and in gastrointestinal stromal tumours

Journal of Cellular and Molecular Medicine — Fri, 27 Jan 2012 21:50:41 +0100

AbstractENDOGLIN/CD105 (ENG) is a transmembrane glycoprotein and an auxiliary unit of the transforming growth factor‐β (TGF‐β); receptor, expressed predominantly in vascular endothelium. Noteworthy, Eng mRNA expression has been reported also in Kit+ interstitial cells of Cajal (ICC) in the mouse intestine. Gastrointestinal stromal tumours (GIST) are thought to derive from ICC. Here we have investigated Eng expression in the KitK641E mouse GIST model, in human GIST and in the Ba/F3 cell model. In wild type (WT) mouse antrum, Eng immunoreactivity (‐ir) was detected in CD34+/CD31+ endothelium and in Kit+ ICC. In KitK641E mice, hyperplasia of Kit+ cells made Eng‐ir even more evident. Quantitative PCR confirmed the increased expression of Eng transcript in KitK641E mice. On human GIST...

Late Effects in Cancer Survivors: “The Shared Care Model”

Current Oncology Reports — Fri, 27 Jan 2012 17:52:49 +0100

Abstract Advances continue to be made in the field of pediatric oncology ever since treatment for childhood cancer began in 1948. Since then, there has been exponential progress in the care for children with cancer as reflected in the current survival rates, which approach 90%. With such incredible survival rates, the number of childhood cancer survivors has increased significantly, with present estimates being above 300,000 in the United States alone. This success has, however, not been without cost. Long-term studies of cancer survivors have brought to light specific adverse effects of therapy, which often present years after treatment is finished, termed “late effects.” Over the years, it has become apparent that monitoring for and treating these late effects of tre...

Oncotype DX testing a winner for guiding breast cancer therapy

PharmacoEconomics and Outcomes News — Fri, 27 Jan 2012 15:13:30 +0100

(Source: PharmacoEconomics and Outcomes News)

Mathematically Modeling Tumor-Immune Interactions To Aid Cancer Therapy

Health News from Medical News Today — Fri, 27 Jan 2012 08:00:00 +0100

Cancer is one of the five leading causes of death. And yet, despite decades of research, there is no standardized first-line treatment for most cancers. In addition, disappointing results from predominant second-line treatments like chemotherapy have established the need for alternative methods. Mathematical modeling of cancer usually involves describing the evolution of tumors in terms of differential equations and stochastic or agent-based models, and testing the effectiveness of various treatments within the chosen mathematical framework... (Source: Health News from Medical News Today)

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Immunological mechanisms of oncolytic adenoviral therapy

EurekAlert! - Biology — Fri, 27 Jan 2012 05:00:00 +0100

(Science in China Press) The use of oncolytic adenovirus provides a novel attractive strategy for cancer therapy, but the mechanisms underlying the therapeutic effects are complicated and largely unknown. A paper in the first issue of Vol. 57 of Chinese Science Bulletin demonstrates that the therapeutic effects of oncolytic adenovirus depend on the CD8+ T cell response. (Source: EurekAlert! - Biology)

Obesity in patients with Acute Lymphoblastic Leukemia in childhood

Italian Journal of Pediatrics — Fri, 27 Jan 2012 05:00:00 +0100

Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to ca...

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

BMC Cancer — Thu, 26 Jan 2012 05:00:00 +0100

Conclusions: We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin. (Source: BMC Cancer)

Anti-miR-155 oligonucleotide enhances chemosensitivity of U251 cell to taxol by inducing apoptosis.

Cell Biology International — Thu, 26 Jan 2012 05:00:00 +0100

Authors: Meng W, Jiang L, Lu L, Hu H, Yu H, Ding D, Xiao K, Zheng W, Guo H, Ma W Abstract Substantial data indicate that the oncogene microRNA-155 is significantly elevated in glioblastoma multiforme (GBM) and regulates multiple genes associated with cancer cell proliferation, apoptosis, and invasiveness. Thus, miR-155 can theoretically become a target to enhance the chemotherapeutic effect in cancer therapy. So far, the effect of down-regulating miR-155 to enhance the chemotherapeutic effect to taxol has not been studied in human GBM. Human GBM U251 cell were treated with taxol and the miR-155 inhibitor, alone or in combination. The 50% inhibitory concentration and cell viability were determined by the MTT assay. Annexin V/PI staining was performed, and apoptosis and the cell cycl...

Aiding cancer therapy by mathematically modeling tumor-immune interactions

EurekAlert! - Medicine and Health — Wed, 25 Jan 2012 05:00:00 +0100

(Society for Industrial and Applied Mathematics) A paper published last month in the SIAM Journal on Applied Mathematics proposes a differential equation model to describe tumor-immune interactions. (Source: EurekAlert! - Medicine and Health)

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Hsp90 inhibition differentially destabilises MAP kinase and TGF-beta signalling components in cancer cells revealed by kinase-targeted chemoproteomics

BMC Cancer — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions: We propose a high confidence list of Hsp90 kinase clients, which provides new opportunities for targeted and combinatorial cancer treatment and diagnostic applications. (Source: BMC Cancer)

Multifunctional QD-based co-delivery of siRNA and doxorubicin to HeLa cells for reversal of multidrug resistance and real-time tracking.

Biomaterials — Tue, 24 Jan 2012 13:00:33 +0100

In this study, two CdSe/ZnSe QDs modified with β-CD coupled to L-Arg or L-His were used to simultaneously deliver doxorubicin (Dox) and siRNA targeting the MDR1 gene to reverse the multidrug resistance of HeLa cells. In this co-delivery system, Dox was firstly encapsulated into the hydrophobic cavities of β-CD, resulting in bypass of P-glycoprotein (P-gp)-mediated drug efflux. After complex formation of the mdr1 siRNA with Dox-loaded QDs via electrostatic interaction, significant down-regulation of mdr1 mRNA levels and P-gp expression was achieved as shown by RT-PCR and Western blotting experiments, respectively. The number of apoptotic HeLa cells after treatment with the complexes substantially exceeded the number of apoptotic cells induced by free Dox only. The intrinsic fluorescence o...

Effects of the inhibition of cytosolic phospholipase A2α in non-small cell lung cancer cells

Journal of Cancer Research and Clinical Oncology — Tue, 24 Jan 2012 12:27:13 +0100

Conclusions Pyrrolidine-2 is a more potent and specific cPLA2α inhibitor than MAFP and AACOCF3 and represents an excellent pharmacological tool to investigate the biosynthesis and the biological roles of cancer. The present study suggests that pyrrolidine-2 could be a potential therapeutic agent for cancer therapy. Content Type Journal ArticleCategory Original PaperPages 1-9DOI 10.1007/s00432-012-1157-7Authors Shenbagamoorthy Sundarraj, Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, 641046 TN, IndiaSoundarapandian Kannan, Proteomics and Molecular Cell Physiology Laboratory, Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, 641046 TN, IndiaRamar ...

p53 is not directly relevant to the response of Polo-like kinase 1 inhibitors.

Cell Cycle — Tue, 24 Jan 2012 09:52:05 +0100

In this study, we demonstrate that there is no obvious different cytotoxic response between cancer cells with and without functional p53, including the isogenic colon cancer cell lines HCT116p53(+/+) and HCT116p53(-/-), breast cancer cell line MCF7, lung cancer cell line A549 and cervical carcinoma cell line HeLa, after treatment with either siRNA against Plk1, the kinase domain inhibitors BI 2536 and BI 6727 or the PBD inhibitor Poloxin. We suggest that the p53 status is not a predictor for the response of Plk1 inhibition, at least not directly. Yet, the long-term outcomes of losing p53, such as genome instability, could be associated with the cytotoxicity of Plk1 inhibition. Further studies are required to investigate whether other circumstances of cancer cells, such as DNA replication/d...

Georgetown University Medical Center licenses 'theranostic' for development

EurekAlert! - Medicine and Health — Tue, 24 Jan 2012 05:00:00 +0100

(Georgetown University Medical Center) Georgetown University Medical Center has licensed worldwide rights of a potential novel cancer therapy and diagnostic, or "theranostic," to BioMetrx, LLC. The agent was invented by two Georgetown researchers. (Source: EurekAlert! - Medicine and Health)

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First identification of small molecule inhibitors of Pontin by combining virtual screening and enzymatic assay

BJ Disease — Tue, 24 Jan 2012 05:00:00 +0100

The human protein Pontin, which belongs to the AAA+ family, is overexpressed in several cancers and its silencing in vitro leads to tumor cell growth arrest and apoptosis, making it a good target for cancer therapy. In particular, high levels of expression were found in hepatic tumors for which the therapeutic arsenal is rather limited. The 3D structure of Pontin had previously been resolved, revealing an hexameric assembly with one ADP molecule co-crystallized in each subunit. Using Vina, Drugscore and Xscore, structure-based virtual screening of 2,200 commercial molecules was conducted into the ATP binding site formed by a dimer of Pontin in order to prioritize the best candidates. Complementary to the in silico screening, a versatile and sensitive colorimetric assay was set up to...

The rheological properties of different GNPs

Lipids in Health and Disease — Tue, 24 Jan 2012 05:00:00 +0100

Conclusions: The torque%, viscosity (cp) and SS (dyne/cm2) of all GNP sizes decreased with increasing the temperature and with decreasing the GNP size (for each fixed temperature value). For each shear rate value, the viscosity of all GNPs decreased with decreasing the GNP size. This study demonstrates that the physical, dimensional and morphological changes of GNPs have effective influence on their rheological properties. To understand and categorize the role of GNPs in drug delivery and cancer therapy, GNPs of varying size, number of particles, shape and surface should be taken into consideration. Moreover, further additional in vivo studies after administration of GNPs in rats should be performed to support this hypothesis. (Source: Lipids in Health and Disease)

Rowley to receive Japan Prize for her role in the development of targeted cancer therapy

EurekAlert! - Cancer — Tue, 24 Jan 2012 05:00:00 +0100

(University of Chicago Medical Center) The University of Chicago's Janet Rowley will share the 2012 Japan Prize for Healthcare and Medical Technology with Brian Druker, OHSU, and Nicholas Lydon, Ph.D., Novartis, for their roles in the development of the first precisely targeted anti-cancer drug, Gleevec. The recipients, "have made significant contributions to society by achieving momentous scientific and technological breakthroughs." They will receive a Certificate of Merit, a Japan Prize Medal and a share of 50 million Japanese yen. (Source: EurekAlert! - Cancer)

BMP‐2 inhibits tumor growth of human renal cell carcinoma and induces bone formation

International Journal of Cancer — Tue, 24 Jan 2012 05:00:00 +0100

This study investigates the effect of BMP‐2 on human renal cell carcinoma using ACHN and Caki‐2 cell lines. Three types of BMP receptors were found to be expressed in ACHN and Caki‐2 cells. In vitro, BMP‐2 was found to inhibit the growth of ACHN and Caki‐2 cells. The antiproliferative effect seems to be due to cell cycle arrest in the G1 phase, which was revealed by flow cytometry analysis. Using RT‐PCR analysis, we demonstrated BMP‐2 up‐regulated osteogenic markers Runx‐2 and Collagen Type I gene expression in ACHN and Caki‐2 cells. Treatment of ACHN and Caki‐2 cells with BMP‐2 induced a rapid phosphorylation of Smad1/5/8. In vivo, all animals receiving low number of ACHN (1×104) and Caki‐2 (5×104) cells treated with 30 μg BMP‐2 per animal showed limited tum...

The potential for Cerenkov luminescence imaging of alpha-emitting radionuclides.

Physics in Medicine and Biology — Mon, 23 Jan 2012 08:30:39 +0100

Authors: Ackerman NL, Graves EE Abstract Targeted α-emitting drugs are promising for cancer therapy, but cannot be effectively imaged by conventional techniques. Cerenkov luminescence imaging (CLI) has previously been shown capable of imaging β(+)- and β(-)-emitting radionuclides in vivo and could have the potential to image α-emitters. Cerenkov light production from α-emitters is through Compton scattering and from farther down the decay chain. This causes the Cerenkov production to vary in time and depend on sample geometry, complicating the interpretation of CLI images. We used the simulation toolkit Geant4 to predict the Cerenkov light output from five α-emitting radionuclides that have therapeutic potential: (225)Ac, (230)U, (213)Bi, (212)Bi and (212)At. We found that (2...

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Controlling cancer through the autotaxin-lysophosphatidic acid receptor axis.

Biochemical Society Transactions — Sun, 22 Jan 2012 22:31:40 +0100

Authors: Gotoh M, Fujiwara Y, Yue J, Liu J, Lee S, Fells J, Uchiyama A, Murakami-Murofushi K, Kennel S, Wall J, Patil R, Gupte R, Balazs L, Miller DD, Tigyi GJ Abstract LPA (lysophosphatidic acid, 1-acyl-2-hydroxy-sn-glycero-3-phosphate), is a growth factor-like lipid mediator that regulates many cellular functions, many of which are unique to malignantly transformed cells. The simple chemical structure of LPA and its profound effects in cancer cells has attracted the attention of the cancer therapeutics field and drives the development of therapeutics based on the LPA scaffold. In biological fluids, LPA is generated by ATX (autotaxin), a lysophospholipase D that cleaves the choline/serine headgroup from lysophosphatidylcholine and lysophosphatidylserine to generate LPA. In the pre...

[News Focus] Clinical Trials: Experimental Cancer Therapies Move to the Front Line

Science: Current Issue — Sat, 21 Jan 2012 17:26:17 +0100

It's standard to test drugs in advanced cancer; now, some doctors are using experimental drugs earlier in disease and juggling the challenges that come with doing so.Author: Jennifer Couzin-Frankel (Source: Science: Current Issue)

[Podcast] Science Podcast

Science: Current Issue — Sat, 21 Jan 2012 17:26:17 +0100

The show includes a Sun-grazing comet, protecting against the shiga toxin, the risks of experimental cancer therapies, and more. (Source: Science: Current Issue)

Adverse Effects of GI Cancer Therapy Long-Lasting

MedPage Today Hematology/Oncology — Fri, 20 Jan 2012 20:43:07 +0100

SAN FRANCISCO (MedPage Today) -- Years after successful treatment for gastric or esophageal cancer, patients still have complications from therapy, researchers found. (Source: MedPage Today Hematology/Oncology)

Apoptosis and survival

Indian Journal of Human Genetics — Fri, 20 Jan 2012 05:00:00 +0100

Manjul TiwariIndian Journal of Human Genetics 2011 17(3):120-125The term apoptosis first appeared in the biomedical literature in 1972, to delineate a structurally distinctive mode of cell death responsible for cell loss within living tissues. The cardinal morphological features are cell shrinkage, accompanied by transient but violent bubbling and blebbing from the surface, and culminating in separation of the cell into a cluster of membrane-bounded bodies. Changes in several cell surface molecules also ensure that, in tissues, apoptotic cells are immediately recognised and phagocytosed by their neighbours. However, it is important to note that apoptosis is only one form of cell death and the particular death pathway that is the most important determinant for cancer therapy is not necessar...

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Activation of lytic cycle of Epstein‐Barr virus by suberoylanilide hydroxamic acid leads to apoptosis and tumor growth suppression of nasopharyngeal carcinoma

International Journal of Cancer — Thu, 19 Jan 2012 05:00:00 +0100

We reported that suberoylanilide hydroxamic acid (SAHA) induced EBV lytic cycle in EBV‐positive gastric carcinoma cells and mediated enhanced cell death. However, expression of EBV lytic proteins was thought to exert anti‐apoptotic effect in EBV‐infected cells. Here, we examined the in vitro and in vivo effects of SAHA on EBV lytic cycle induction in NPC cells and investigated the cellular consequences. Micromolar concentrations of SAHA significantly induced EBV lytic cycle in EBV‐positive NPC cells. Increased apoptosis and proteolytic cleavage of PARP, caspase‐3, ‐7 and ‐9 in EBV‐positive versus EBV‐negative NPC cells were observed. >85% of NPC cells expressing immediate‐early (Zta), early (BMRF1) or late (gp350/220) lytic proteins co‐expressed cleaved caspase‐3...

The interplay of HER2/HER3/PI3K and EGFR/HER2/PLC‐γ1 signalling in breast cancer cell migration and dissemination

The Journal of Pathology — Thu, 19 Jan 2012 05:00:00 +0100

AbstractHER2 signalling by heterodimerization with EGFR and HER3 in breast cancer is associated with worst outcome of the afflicted patients, which is not only attributed to the aggressiveness of such tumours, but also to therapy resistance. In the present study we thus investigated the role of EGFR, HER2, and HER3 lateral signalling in cell migration by applying the MDA‐MB‐468‐HER2 (MDA‐HER2) breast cancer cell line representing a valid model system. Knockdown of HER3 expression by siRNA resulted in decreased pAKT levels, abrogated EGF‐mediated PLC‐?1 activation, and a diminished EGF‐induced migratory activity depicting the interplay of EGFR/HER2/PLC‐?1 and HER2/HER3/PI3K signalling in mediating the migration of EGFR/HER2/HER3 expressing breast cancer cells. Since therapy ...

Autophagy and Cancer.

exp Mol Med — Thu, 19 Jan 2012 05:00:00 +0100

Authors: Choi KS Abstract Basal autophagy plays a critical role in maintaining cellular homeostasis and genomic integrity by degrading aged or malfunctioning organelles and damaged or misfolded proteins. However, autophagy also plays a complicated role in tumorigenesis and treatment responsiveness. It can be tumor-suppressing during the early stages of tumorigenesis (i.e., it is an anti-tumor mechanism), as reduced autophagy is found in tumor cells and may be associated with malignant transformation. In this case, induction of autophagy would seem to be beneficial for cancer prevention. In established tumors, however, autophagy can be tumor-promoting (i.e., it is a pro-tumor mechanism), and cancer cells can use enhanced autophagy to survive under metabolic and therapeutic stress. T...

Regulation of HGF-mediated cell proliferation and invasion through NF-κB, JunB, and MMP-9 cascades in stomach cancer cells

Clinical and Experimental Metastasis — Wed, 18 Jan 2012 06:48:28 +0100

In conclusion, these results may contribute to the JunB-associated malignant phenotype of gastric cancers by regulating MMP-9, and serve as a novel therapeutic target for stomach cancer therapy in the future. Content Type Journal ArticleCategory Research PaperPages 1-10DOI 10.1007/s10585-011-9449-xAuthors Kyung Hee Lee, Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu, Republic of KoreaJae-Ryong Kim, Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong, Daegu, 705-717 Republic of Korea Journal Clinical and Experimental MetastasisOnline ISSN 1573-7276Print ISSN 0262-0898 (Source: Clinical and Experimental Metastasis)

Neutrophil gelatinase–associated lipocalin regulates intracellular accumulation of Rh123 in cancer cells

Genes to Cells — Wed, 18 Jan 2012 05:00:00 +0100

Multidrug resistance (MDR) is a major problem facing patients with cancer. Although Neutrophil gelatinase–associated lipocalin (NGAL) is highly expressed in various cancers, the possible role of NGAL in MDR is still obscure. In this article, we evaluated the effect of NGAL on Rh123 accumulation in cancer cells. NGAL was first down‐regulated by short hairpin RNA–mediated interference. In correlation with the reduced NGAL expression, intracellular Rh123 accumulation was significantly decreased. We finally observed that inhibiting both of the ERK1/2 and p38 MAPK could seriously down‐regulate NGAL expression and also decrease the intracellular accumulation of Rh123, indicating that NGAL‐mediated Rh123 accumulation is regulated by the phosphorylation of ERK1/2 and p38 MAPK. Pretreatme...

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A poly(glycerol-sebacate-(5-fluorouracil-1-acetic acid)) polymer with potential use for cancer therapy

Journal of Bioactive and Compatible Polymers — Wed, 18 Jan 2012 05:00:00 +0100

In this study, 5-fluorouracil-1-acetic acid was chemically conjugated with poly(glycerol-sebacate) (PGS) to form a unitary polymer poly(glycerol-sebacate- (5-fluorouracil-1-acetic acid)) (PGS-5-FU-CH2COOH). The structure, the in vitro antitumor activity of 5-FU-CH2COOH, the in vitro degradation, the drug release, and antitumor activity as well as the in vivo degradation and tissue biocompatibility of PGS-5-FU-CH2COOH were investigated. The 5-FU-CH2COOH inhibited HeLa (human cervical cancer cell line) and SGC-7901 (human gastric adenocarcinoma cell line) tumor cells with a half maximal inhibitory concentration (IC50) of 0.196 and 0.267 μM, respectively, after a 3-day incubation. The in vitro drug release profiles of PGS-5-FU-CH2COOH exhibited a biphasic release with an initial exponentia...

The DNA damage response and cancer therapy

Nature — Wed, 18 Jan 2012 05:00:00 +0100

Authors: Christopher J. Lord & Alan Ashworth Genomic instability is one of the most pervasive characteristics of tumour cells and is probably the combined effect of DNA damage, tumour-specific DNA repair defects, and a failure to stop or stall the cell cycle before the damaged DNA is passed on to daughter cells. (Source: Nature)

Construct validity of the EORTC quality of life questionnaire information module

Quality of Life Research — Tue, 17 Jan 2012 07:08:41 +0100

Conclusion The suggested construct of the INFO25 with a total score (general factor) in addition to the subscales is valid. Content Type Journal ArticlePages 1-7DOI 10.1007/s11136-012-0114-xAuthors Susanne Singer, Department of Medical Psychology and Medical Sociology, University of Leipzig, Philipp-Rosenthal-Str. 55, 04103 Leipzig, GermanyPhilipp M. Engelberg, Department of Methods and Psychodiagnostics, University of Wuppertal, Wuppertal, GermanyGregor Weißflog, Department of Medical Psychology and Medical Sociology, University of Leipzig, Philipp-Rosenthal-Str. 55, 04103 Leipzig, GermanySusanne Kuhnt, Department of Medical Psychology and Medical Sociology, University of Leipzig, Philipp-Rosenthal-Str. 55, 04103 Leipzig, GermanyJochen Ernst, Department of Medical Psy...

Enlightening the impact of immunogenic cell death in photodynamic cancer therapy

The EMBO Journal AOP — Tue, 17 Jan 2012 05:00:00 +0100

Authors: Lorenzo Galluzzi, Oliver Kepp & Guido Kroemer In this issue of The EMBO Journal, Garg et al (2012) delineate a signalling pathway that leads to calreticulin (CRT) exposure and ATP release by cancer cells that succumb to photodynamic therapy (PTD), thereby providing fresh insights into the molecular regulation of immunogenic cell death (ICD). (Source: The EMBO Journal AOP)

Histone H3 phosphorylation, immediate-early gene expression, and the nucleosomal response: a historical perspective (1) (1) This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal's usual peer review process.

Biochemistry and Cell Biology — Tue, 17 Jan 2012 05:00:00 +0100

This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal's usual peer review process. Biochem Cell Biol. 2012 Jan 17; Authors: Healy S, Khan P, He S, Davie JR Abstract Histone H3 is modified at serines 10 and 28 in interphase cells following activation of the RAS-MAPK or p38-MAPK pathways by growth factors or stress. These modifications are involved in the regulation of immediate-early genes, including Jun and Fos, whose increased expression is a trademark of various cancers. This review outlines the series of discoveries that led to the characterization of these modifications, the kinase, MSK1/2, which is activated by both MAPK pathways and directs phosphorylation of H3, and the mechanistic function of these modifications in transcrip...

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Negative regulation-resistant p53 variant enhances oncolytic adenoviral gene therapy.

Herpes — Mon, 16 Jan 2012 05:00:00 +0100

Authors: Koo T, Choi IK, Kim M, Lee JS, Oh E, Kim J, Yun CO Abstract Intact p53 function is essential for responsiveness to cancer therapy. However, p53 activity is attenuated by the proto-oncoprotein Mdm2, the adenovirus protein E1B-55kD, and the p53 C-terminal domain. To confer resistance to Mdm2, E1B-55kD, and C-terminal negative regulation, we generated a p53 variant (p53VPΔ30) by deleting the N-terminal and C-terminal regions of wild-type (wt) p53 and inserting the transcriptional activation domain of herpes simplex virus VP16 protein. The oncolytic adenovirus vector Ad-mΔ19 expressing p53VPΔ30 (Ad-m19/p53VPΔ30) showed greater cytotoxicity than Ad-mΔ19 expressing wt p53 or other p53 variants in human cancer cell lines. We found that Ad-m∆19/p53VPΔ30 induced apopt...

Targeting MicroRNA-196a by a Plasmid-based Antagomir for Pancreatic Cancer Therapy

Journal of Surgical Research — Sat, 14 Jan 2012 22:30:09 +0100

(Source: Journal of Surgical Research)

A Novel Role for Myeloid Derived Suppressor Cells in Tumor-specific Therapeutic Targeting

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:58 +0100

Introduction: The major challenge to effective oncolytic viral-mediated cancer therapy is the lack of tumor-specific targeting. Myeloid derived suppressor cells (MDSCs) are immature myeloid cells induced by tumor factors which have been shown to migrate to tumors. Better understanding of the kinetics of MDSC migration may enable the use of MDSCs as delivery vectors for tumor-specific therapies. Vesicular Stomatitis Virus (VSV) is an oncolytic rhabdovirus which requires high doses for effective peripherally administered cancer therapy. These doses carry a likelihood of neurotoxic effects in humans. We hypothesize that MDSCs can improve delivery and decrease side effects of VSV therapy. Methods: Ly6C+ monocytic MDSCs were isolated from tumor-bearing BALB/c mice. Cells were stained with Ferid...

Combination of TRAIL and JAK-2 Downregulation: Novel Therapeutic Strategy Against Pancreatic Cancer

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:04 +0100

Conclusions: Inhibition of JAK-2 pathway sensitizes pancreatic cancer cells to TRAIL induced apoptosis and cell death. Combination of JAK-2 silencing and TRAIL has immense potential to emerge as novel therapeutic strategy against pancreatic cancer. (Source: Journal of Surgical Research)

Immunohistochemistry: Relevance in dermatology

Indian Journal of Dermatology — Sat, 14 Jan 2012 05:00:00 +0100

Aparna Palit, Arun C InamadarIndian Journal of Dermatology 2011 56(6):629-640Use of immunohistochemical technique is increasing in diagnosing various diseases. In many situations it may not be possible to differentiate entities with overlapping clinical and histopathological features. Immunostaining of cellular antigens is immensely helpful in such cases. Immunohistochemistry (IHC) has also been in use for targeted cancer therapy. In this article, the discussion will be restricted to use of IHC in dermatological disorders and use of classical antigens with brief updating of some important newly discovered antigens. (Source: Indian Journal of Dermatology)

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Anticancer Properties of Pomolic Acid-Induced AMP-Activated Protein Kinase Activation in MCF7 Human Breast Cancer Cells.

Biological and Pharmaceutical Bulletin — Fri, 13 Jan 2012 09:48:02 +0100

In this study, we investigated PA activated AMPK, and this activity was related to proliferation and apoptosis in MCF7 breast cancer cells. PA inhibited cell proliferation and induced sub-G(1) arrest, elevating the mRNA levels of the apoptotic genes p53 and p21. PA activated caspase-3, -9, and poly(ADP-ribose) polymerase, and this effect was inhibited by z-VAD-fmk. AMPK activation was increased by treating cells with PA, inactivated by treating cells with a compound C, and co-treatment consisting of PA and aminoimidazole carboxamide ribonucleotide (AICAR) synergistically activated AMPK. These anti-cancer potentials of PA were accompanied by effects on de novo fatty acid synthesis as shown by the decreased expression of fatty acid synthase, and decreased acetyl-CoA carboxylase activation an...

Treatment with targeted vesicular stomatitis virus generates therapeutic multifunctional anti-tumor memory CD4 T cells

Cancer Gene Therapy — Fri, 13 Jan 2012 05:00:00 +0100

Authors: Y Gao, P Whitaker-Dowling, J A Griffin & I Bergman (Source: Cancer Gene Therapy)

Androgen Stimulation of TORC2 [Cell Biology]

Journal of Biological Chemistry — Fri, 13 Jan 2012 05:00:00 +0100

This study reveals a pathway linking AR to a selective activation of TORC2, the subsequent activation of AKT, and phosphorylation of a discrete set of AKT substrates that regulate cellular proliferation and survival. These findings establish that TORC2 can function as a central regulator of growth in response to signals that are distinct from those regulating TORC1, and support efforts to target TORC2 for cancer therapy. (Source: Journal of Biological Chemistry)

Senescence: a new weapon for cancer therapy.

Trends in Cell Biology — Fri, 13 Jan 2012 05:00:00 +0100

Authors: Acosta JC, Gil J Abstract Senescence is a stable cell cycle arrest that can be activated by oncogenic signaling and manifests with changes in cellular organization and gene expression, such as the induction of a complex secretome. Importantly, senescence limits tumor progression and determines the outcome of conventional anticancer therapies. In recent years, therapeutic approaches such as p53 reactivation, inhibition of c-MYC in addicted tumors or treatment with cyclin-dependent kinase (CDK) inhibitors have proven effective by invoking a senescence response. The possibility of using prosenescence therapies for cancer treatment has provoked considerable interest. We propose that the senescence secretome can be a source of novel targets for prosenescence therapies, as it ha...

Contrast CT, PET/CT assess cancer therapy for melanoma

AuntMinnie.com Headlines — Thu, 12 Jan 2012 19:43:00 +0100

Dynamic contrast-enhanced CT and FDG-PET/CT can provide additional information (more) (Source: AuntMinnie.com Headlines)

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Science Podcast, 20 January 2012

Science Magazine Podcast — Thu, 12 Jan 2012 18:59:59 +0100

Watching a comet evaporate in the Sun’s atmosphere; manganese as protection against the Shiga toxin; experimental cancer therapies in early-stage cancers; and more. (Source: Science Magazine Podcast)

Formulating dual-function nanoparticles for photodynamic and photothermal cancer therapy

Nanotechweb.org journal highlights — Thu, 12 Jan 2012 14:35:13 +0100

Carbon nanotube–chitosan–phycocyanin complex displays photoinduced cytoxicity (Source: Nanotechweb.org journal highlights)

Therapeutic efficacy and toxicity of 225Ac-labelled vs. 213Bi-labelled tumour-homing peptides in a preclinical mouse model of peritoneal carcinomatosis

European Journal of Nuclear Medicine and Molecular Imaging — Thu, 12 Jan 2012 06:42:35 +0100

Conclusion Therapy with both 225Ac-DOTA-F3 and 213Bi-DTPA-F3 increased survival of mice with peritoneal carcinomatosis. Mild renal toxicity of both constructs favours future therapeutic application. Content Type Journal ArticleCategory Original ArticlePages 1-11DOI 10.1007/s00259-011-2023-6Authors Markus Essler, Department of Nuclear Medicine, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, GermanyFlorian C. Gärtner, Department of Nuclear Medicine, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, GermanyFrauke Neff, Institute of Pathology, Helmholtz Zentrum München, Neuherberg, GermanyBirgit Blechert, Department of Nuclear Medicine, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, GermanyReingard Se...

Expression and glucocorticoid-regulation of "Bam", a novel BH3-only transcript in acute lymphoblastic leukemia.

Molecular Biology Reports — Thu, 12 Jan 2012 05:00:00 +0100

Expression and glucocorticoid-regulation of "Bam", a novel BH3-only transcript in acute lymphoblastic leukemia. Mol Biol Rep. 2012 Jan 12; Authors: Mansha M, Wasim M, Kofler A, Ploner C Abstract Apoptosis is a morphologically defined form of cell death that plays a major role in cell physiology, pathology and cancer therapy. The Bcl-2 family of pro- and anti-apoptotic molecules is a key regulator of this phenomenon, with the sub-family of BH3-only molecules serving as activators and/or facilitators. Apoptosis induced by glucocorticoids (GC) is a central component in the therapy of acute lymphoblastic leukemia (ALL), and defining its molecular basis and that of GC resistance is crucial for therapeutic improvements. We recently identified a novel transcript from the BCL2L11/B...

Dietary calcium supplementation enhances efficacy but also toxicity of EGFR inhibitor therapy for colon cancer.

Cancer Biology and Therapy — Thu, 12 Jan 2012 04:00:12 +0100

Authors: Rinella E, Bankaitis E, Threadgill D Abstract The inverse correlation between levels of dietary calcium and colorectal cancer (CRC) incidence has been extensively investigated. However, the impact of supplemental calcium on cancer therapy remains unknown. We used four models of CRC, Caco-2 and HCT116 human cancer cell lines and ApcMin/+ and azoxymethane carcinogen-induced mouse models, to investigate the impact of a western-style diet low in calcium (0.05%) versus a similar diet but supplemented with calcium (5%) on therapeutic targeting of the epidermal growth factor receptor (EGFR). We found that calcium supplementation combined with pharmacologic blockade of EGFR results in an additive effect on tumor growth inhibition in all models. Unexpectedly, the combined use of di...

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Estrogen receptor β (ERβ) is a novel prognostic marker of recurrence survival in non-muscle-invasive bladder cancer potentially by inhibiting cadherin switch

World Journal of Urology — Wed, 11 Jan 2012 17:52:25 +0100

Conclusion ERβ is a prognostic marker of recurrence-free rate in non-muscle-invasive bladder cancer, potentially through suppressing cadherin switch, and may act as a potential target for bladder cancer therapy. Content Type Journal ArticleCategory Original ArticlePages 1-7DOI 10.1007/s00345-011-0819-4Authors Bangmin Han, Department of Urology, School of Medicine, The First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaDi Cui, Department of Urology, School of Medicine, The First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaYifeng Jing, Department of Urology, School of Medicine, The First People’s Hospital Affiliated to Shanghai Jiao Tong University, S...

Survivin in Solid Tumors: Rationale for Development of Inhibitors

Current Oncology Reports — Wed, 11 Jan 2012 06:57:59 +0100

Abstract Survivin is a 16.5 kDa protein that functions to inhibit apoptosis, promote proliferation, and enhance invasion. Absent in most adult tissues, survivin is selectively upregulated in many human tumors, where its overexpression correlates with poor outcome and treatment resistance. Consequently, survivin is a promising target for cancer therapy. Preclinical data demonstrate that survivin inhibition reduces cell proliferation, increases apoptosis, and sensitises cells to cytotoxic agents and radiotherapy. The pharmacological survivin inhibitors LY2181308 and YM155 have demonstrated acceptable toxicity and evidence of therapeutic efficacy as single agents in early-phase clinical trials. Current efforts seek to define the optimum use of survivin inhibitors in comb...

Progress in Cancer Therapy

Cancer Biotherapy and Radiopharmaceuticals — Tue, 10 Jan 2012 20:26:29 +0100

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0. (Source: Cancer Biotherapy and Radiopharmaceuticals)

Health-related quality of life, psychological distress, and adverse events in postmenopausal women with breast cancer who receive tamoxifen, exemestane, or anastrozole as adjuvant endocrine therapy: National Surgical Adjuvant Study of Breast Cancer 04 (N-SAS BC 04)

Breast Cancer Research and Treatment — Tue, 10 Jan 2012 16:49:30 +0100

Abstract Health-related quality of life (HRQOL), symptoms of depression, and adverse events (AEs) were compared between Japanese postmenopausal patients with hormone-sensitive breast cancer (BC) who received adjuvant tamoxifen, exemestane, or anastrozole in an open-labeled, randomized, multicenter trial designated as the National Surgical Adjuvant Study of Breast Cancer (N-SAS BC) 04 substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. During the first year of treatment, HRQOL and symptoms of depression were analyzed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and its Endocrine Symptom Subscale (ES), and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. In addition, predefined AEs were analyzed. A total ...

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Use of anti-cancer drugs, mitocans, to enhance the immune responses against tumors.

Current Pharmaceutical Biotechnology — Tue, 10 Jan 2012 15:30:38 +0100

Authors: Hahn T, Polanczyk MJ, Borodovsky A, Ramanathapuram LV, Akporiaye ET, Ralph SJ Abstract Cytotoxic drugs in cancer therapy are used with the expectation of selectively killing and thereby eliminating the offending cancer cells. If they should die in an appropriate manner, the cells can also release danger signals that promote an immune reaction that reinforces the response against the cancer. The identity of these immune-enhancing danger signals, how they work extra- and intracellularly, and the molecular mechanisms by which some anti-cancer drugs induce cell death to bring about the release of danger signals are the major focus of this review. A specific group of mitocans, the vitamin E analogs that act by targeting mitochondria to drive ROS production and also promote a mo...

Dako and Amgen to Collaborate in Development of A Companion Diagnostic for An Amgen Investigational Cancer Therapy

Drugs.com - Pharma News — Tue, 10 Jan 2012 15:03:24 +0100

Dako, a world leading independent cancer diagnostic supplier with 45 years of experience in pathology, announced today that it has entered into a development and collaboration agreement with Amgen Inc. (Nasdaq: AMGN) to develop a diagnostic test for... (Source: Drugs.com - Pharma News)

Analysis of the pharmacodynamic activity of the mTOR inhibitor ridaforolimus (AP23573, MK-8669) in a phase 1 clinical trial

Cancer Chemotherapy and Pharmacology — Mon, 09 Jan 2012 19:37:50 +0100

Conclusions Ridaforolimus was shown to inhibit its intended target, mTOR, in PBMCs, skin, and tumors. In PBMCs and skin, inhibition was observed at all dose levels tested, thus supporting but not driving the selection of a recommended phase 2 dose. Content Type Journal ArticleCategory Clinical Trial ReportPages 1-9DOI 10.1007/s00280-011-1813-7Authors Lori Berk, ARIAD Pharmaceuticals, Inc., 26 Landsdowne Street, Cambridge, MA 02139, USAMonica M. Mita, Cancer Therapy and Research Center, Institute for Drug Development, The University of Texas Health Science Center, San Antonio, TX, USAJeff Kreisberg, Cancer Therapy and Research Center, Institute for Drug Development, The University of Texas Health Science Center, San Antonio, TX, USACamille L. Bedrosian, ARIAD Pharmace...

The quality of sexual life in women with gynaecological cancers

Archives of Gynecology and Obstetrics — Mon, 09 Jan 2012 19:35:21 +0100

Conclusions According to the results obtained from the study, it can be stated that the sexual quality of life of women with gynaecological cancers is moderate and social support, especially support from a significant person, may affect quality of sexual life positively. Content Type Journal ArticleCategory Gynecologic OncologyPages 1-5DOI 10.1007/s00404-011-2210-5Authors Zehra Golbasi, Department of Nursing, Faculty of Health Sciences, Cumhuriyet University, Sivas, TurkeyAyten Senturk Erenel, Department of Nursing, Faculty of Health Sciences, Gazi University, Ankara, Turkey Journal Archives of Gynecology and ObstetricsOnline ISSN 1432-0711Print ISSN 0932-0067 (Source: Archives of Gynecology and Obstetrics)

Proteomics analysis of in vitro protein methylation during Src‐induced transformation

Electrophoresis — Mon, 09 Jan 2012 05:00:00 +0100

In this study, we determined if protein methylation was involved in Src activation and which methylated proteins were associated with this activity. Using in vitro methylation and 2‐DE analysis of viral Src (v‐Src)‐transformed rat kidney epithelial cells (RK3E), several known and novel methylated proteins were identified based on their changes in methylation signal intensity upon transformation. Among these, elongation factor 2 (EF‐2), heterogeneous nuclear ribonucleoprotein K (hnRNP K), and β‐tubulin protein expressions remained unchanged, indicating that their altered methylation levels were due to Src activation. In addition, the altered expression of β‐actin, vimentin, and protein phosphatase 2, catalytic subunit (PPP2C) as well as protein phosphatase 2, catalytic subunit...

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A Self-Report Instrument That Describes Urogenital Atrophy Symptoms in Breast Cancer Survivors

Western Journal of Nursing Research — Mon, 09 Jan 2012 05:00:00 +0100

Urogenital atrophy affects the lower urinary and genital tracts and is responsible for urinary, genital, and sexual symptoms. The accurate identification, measurement, and documentation of symptoms are limited by the absence of reliable and valid instruments. The Urogenital Atrophy Questionnaire was developed to allow self-reporting of symptoms and to provide clinicians and researchers an instrument to identify, measure, and document indicators of urogenital atrophy. A pilot study (n = 30) measured test–retest reliability (p < .05) of the instrument. Subsequently, a survey of women with (n = 168) and without breast cancer (n = 166) was conducted using the Urogenital Atrophy Questionnaire, Female Sexual Function Instrument, and Functional Assessment of Cancer Therapy, Breast, Endoc...

A new development of triterpene acid‐containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia

Cell Proliferation — Sat, 07 Jan 2012 20:57:37 +0100

Conclusion: Here for the first time, we have demonstrated that either solubilized triterpene acids or lectins and combinations thereof, induce dose‐dependent apoptosis in the ALL cell line NALM‐6 via caspase‐8 and ‐9 dependent pathways. (Source: Cell Proliferation)

Zirconium phosphate nano-platelets: a novel platform for drug delivery in cancer therapy

RSC - Chem. Commun. latest articles — Sat, 07 Jan 2012 00:11:51 +0100

Chem. Commun., 2012, Advance ArticleDOI: 10.1039/C2CC16218K, CommunicationAgustin Diaz, Vipin Saxena, Julissa Gonzalez, Amanda David, Barbara Casanas, Carrie Carpenter, James D. Batteas, Jorge L. Colon, Abraham Clearfield, M. Delwar HussainZirconium phosphate nano-platelets (ZrP) were used for delivery of doxorubicin to cancer cells. Cellular uptake studies in cancer cells showed higher uptake and cytotoxicity of doxorubicin loaded ZrP compared to free doxorubicin.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Chem. Commun. latest articles)

January eFactor

Environmental Factor - NIEHS Newsletter — Fri, 06 Jan 2012 22:46:51 +0100

Tox21 begins screening 10,000 chemicals NIEHS collaborates on autism database federation Balbus discusses health adaptation at climate change summit Copeland named chief of Laboratory of Molecular Genetics Grantee honored by association of science teachers Birnbaum and staff hold conversation with NIEHS Partners Nano Grand Opportunities researchers share findings mHealth Summit highlights advances in mobile health technology NIEHS postdocs learn the value of options at NC biotech career day Award-winning summer intern accepted by Stanford Freedman represents NIEHS/NTP at conference in Peru NTP advisor named as fellow of the Collegium Ramazzini Volunteers translate NIEHS cookstove research in Guatemala 2011 papers of the year Distinguished lecturer discusses the mechanism of a...

Dendreon Jumps As 4Q Provenge Sales Improve

Drugs.com - Pharma News — Fri, 06 Jan 2012 15:42:49 +0100

SEATTLE (AP)-Shares of Dendreon Corp. surged Thursday after the company said sales of its prostate-cancer therapy Provenge continued to grow in the fourth quarter. Dendreon said sales of Provenge rose to $82 million in the fourth quarter. FactSet... (Source: Drugs.com - Pharma News)

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In vitro biocompatibility of thermally gelling liquid mucoadhesive loaded curcuminoids in colorectal cancer chemoprevention

International Journal of Colorectal Disease — Fri, 06 Jan 2012 06:43:44 +0100

Conclusion The results have suggested that Poloxamer 407 could be a potential thermogelling and mucoadhesive polymer for the development of a site-targeting colorectal drug delivery system for curcuminoids in colorectal cancer therapy. Figure Poloxamer 407 could be a potential polymer for the development of a site-targeting colorectal drug delivery system (DDS) for curcuminoids in colorectal cancer therapy. Content Type Journal ArticleCategory Original ArticlePages 1-10DOI 10.1007/s00384-011-1393-3Authors Ming-Jenn Chen, Division of Traumatology, Department of Surgery, Chi Mei Medical Center, Tainan, TaiwanYa-Min Cheng, Department of Obstetrics and Gynecology, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, ...

Killing cells by targeting mitosis

Cell Death and Differentiation — Fri, 06 Jan 2012 05:00:00 +0100

Authors: E Manchado, M Guillamot & M Malumbres (Source: Cell Death and Differentiation)

Guidelines for Information About Therapy Experiments: a proposal on best practice for recording experimental data on cancer therapy

BMC Research Notes — Fri, 06 Jan 2012 05:00:00 +0100

Conclusions: While data standards are being developed to facilitate data sharing and integration in various aspects of experimental medicine, such as genomics and clinical data, no previous work focused on therapy development. We propose a checklist for therapy experiments and demonstrate its use in the (131)Iodine labeled CHT-25 chimeric antibody cancer therapy. As future work, we will expand the set of GIATE tools to continue to encourage its use by cancer researchers, and we will engineer an ontology to annotate GIATE elements and facilitate unambiguous interpretation and data integration. (Source: BMC Research Notes)

Next-generation proteasome blockers promise safer cancer therapy

Nature Medicine — Fri, 06 Jan 2012 05:00:00 +0100

Nature Medicine 18, 7 (2012). doi:10.1038/nm0112-7a Author: Asher Mullard (Source: Nature Medicine)

Zirconium phosphate nano-platelets: a novel platform for drug delivery in cancer therapy.

Chemical Communications — Thu, 05 Jan 2012 05:00:00 +0100

Authors: Díaz A, Saxena V, González J, David A, Casañas B, Carpenter C, Batteas JD, Colón JL, Clearfield A, Delwar Hussain M Abstract Doxorubicin was intercalated into novel zirconium phosphate nano-platelets (ZrP). The obtained doxorubicin intercalated ZrP nano-platelets had an impressive 34.9% (w/w) drug loading. We used this material to deliver doxorubicin to breast cancer cells (MCF-7). Cellular studies with MCF-7 cells showed higher uptake and cytotoxicity of doxorubicin loaded ZrP compared to free doxorubicin. PMID: 22218458 [PubMed - as supplied by publisher] (Source: Chemical Communications)

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Glycine Decarboxylase Activity Drives Non-Small Cell Lung Cancer Tumor-Initiating Cells and Tumorigenesis

Cell — Thu, 05 Jan 2012 00:00:00 +0100

Wen Cai Zhang, Ng Shyh-Chang, He Yang, Amit Rai, Shivshankar Umashankar, Siming Ma, Boon Seng Soh, Li Li Sun, Bee Choo Tai, Min En Nga, Kishore Kumar Bhakoo, Senthil Raja Jayapal, Massimo Nichane, Qiang Yu, Dokeu A. Ahmed, Christie Tan, Wong Poo Sing, John Tam, Agasthian Thirugananam, Monireh Soroush Noghabi, Yin Huei Pang, Haw Siang Ang, Paul Robson, Philipp Kaldis, Ross Andrew Soo, Sanjay Swarup, Elaine Hsuen Lim, Bing Lim. Identification of the factors critical to the tumor-initiating cell (TIC) state may open new avenues in cancer therapy. Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is criti.... (Source: Cell)

Echo Guidelines Aim to Minimize Cancer Therapy Toxicity (with audio)

MedPage Today Cardiovascular — Wed, 04 Jan 2012 17:13:01 +0100

(MedPage Today) -- In light of heightened awareness of the cardiovascular damage from cancer treatments, two echocardiography societies are developing guidelines to optimize the use of the imaging modality before and during cancer treatment to minimize cardiac damage. (Source: MedPage Today Cardiovascular)

Oncolytic virotherapy in veterinary medicine: current status and future prospects for canine patients

Journal of Translational Medicine — Wed, 04 Jan 2012 05:00:00 +0100

Oncolytic viruses refer to those that are able to eliminate malignancies by direct targeting and lysis of cancer cells, leaving non-cancerous tissues unharmed. Several oncolytic viruses including adenovirus strains, canine distemper virus and vaccinia virus strains have been used for canine cancer therapy in preclinical studies. However, in contrast to human studies, clinical trials with oncolytic viruses for canine cancer patients have not been reported. An 'ideal' virus has yet to be identified. This review is focused on the prospective use of oncolytic viruses in the treatment of canine tumors - a knowledge that will undoubtedly contribute to the development of oncolytic viral agents for canine cancer therapy in the future. (Source: Journal of Translational Medicine)

Glucose-Independent Glutamine Metabolism via TCA Cycling for Proliferation and Survival in B Cells.

Cell Metabolism — Wed, 04 Jan 2012 05:00:00 +0100

Authors: Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H, Zimmerman LJ, Liebler DC, Slebos RJ, Lorkiewicz PK, Higashi RM, Fan TW, Dang CV Abstract Because MYC plays a causal role in many human cancers, including those with hypoxic and nutrient-poor tumor microenvironments, we have determined the metabolic responses of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using stable isotope-resolved metabolomics. Using [U-(13)C]-glucose as the tracer, both glucose consumption and lactate production were increased by MYC expression and hypoxia. Using [U-(13)C,(15)N]-glutamine as the tracer, glutamine import and metabolism through the TCA cycle persisted under hypoxia, ...

Urinary excretion of 8-oxo-7,8-dihydroguanine as biomarker of oxidative damage to DNA.

Archives of Biochemistry and Biophysics — Wed, 04 Jan 2012 05:00:00 +0100

Authors: Loft S, Danielsen P, Løhr M, Jantzen K, Hemmingsen JG, Roursgaard M, Karotki DG, Møller P Abstract Oxidatively damaged DNA may be important in carcinogenesis. 8-Oxo-7,8-dihydroguanine (8-oxoGua) is an abundant and mutagenic lesion excised by oxoguanine DNA glycosylase 1 (OGG1) and measurable in urine or plasma by chromatographic methods with electrochemical or mass spectrometric detectors, reflecting the rate of damage in steady state. A common genetic OGG1 variant may affect the activity and was associated with increased levels of oxidized purines in leukocytes without apparent effect on 8-oxoGua excretion or major change in cancer risk. 8-OxoGua excretion has been associated with exposure to air pollution, toxic metals, tobacco smoke and low plasma antioxidant levels, ...

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Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer

BMC Cancer — Tue, 03 Jan 2012 05:00:00 +0100

Conclusions: Serum human gonadotropin levels differ in patients with benign and malignant ovarian tumors. HCG is often expressed in ovarian cancer tissue with a certain variable relation to grade and stage.HCG expression correlates with LH-R expression in ovarian cancer tissue, which has previously been shown to be of prognostic value. Both, the hormone and its receptor, may therefore serve as targets for new cancer therapies. (Source: BMC Cancer)

IFN-γ producing T cells contribute to the increase of myeloid derived suppressor cells in tumor-bearing mice after cyclophosphamide treatment.

International Immunopharmacology — Tue, 03 Jan 2012 05:00:00 +0100

Authors: Guo Q, Lv Z, Fu Q, Jiang C, Liu Y, Lai L, Chen Q, Shen J, Wang Q Abstract It has been reported that treatment with cyclophosphamide (CTX) as a chemotherapeutic drug in cancer patients or tumor-bearing mice can result in an increase in the proportion of myeloid derived suppressor cells (MDSCs) in blood and lymphoid organs. Here we sought to clarify the possible mechanism of this unwanted increase in proportion of MDSCs in tumor-bearing mice after CTX treatment. We found that both CD4(+) T cells and CD8(+) T cells underwent an expansion and activation before the increase of MDSCs in the early period of CTX treatment in 4T1 breast tumor-bearing mice. The proportion of MDSCs in nude mice lacking T cells after CTX therapy was comparable to that in nude mice without CTX treatmen...

Finding a Panacea among Combination Cancer Therapies

Cancer Research — Mon, 02 Jan 2012 05:00:00 +0100

Because each cancer is a heterogeneous mix of cancer cells at different stages of development, we are faced with trying to treat many different diseased cells all at once. An authentic approach is to build a genomic and proteomic profile of a patient, identify the target oncogenes, and prescribe the combination of targeted drugs tailored for that patient. However, there are many practical problems with this personalized medicine approach: (i) cancers often generate treatment-resistant phenotypes, (ii) the treatment could be enormously expensive, and (iii) most of the targeted drugs have not been developed yet. We propose a different approach: therapies that combine 2-deoxyglucose (2DG) with Bcl-2 antagonist such as ABT-263/737 (ABT). Proapoptotic protein Bak is normally sequestered by Mcl-...

A Novel Method of Transcriptional Response Analysis to Facilitate Drug Repositioning for Cancer Therapy

Cancer Research — Mon, 02 Jan 2012 05:00:00 +0100

In this study, we addressed this critical gap by developing an OTE-based method to repurpose drugs for cancer therapeutics, based on transcriptional responses made in cells before and after drug treatment. Specifically, we defined a new network component called cancer-signaling bridges (CSB) and integrated it with a Bayesian factor regression model (BFRM) to form a new hybrid method termed CSB-BFRM. Proof-of-concept studies were conducted in breast and prostate cancer cells and in promyelocytic leukemia cells. In each system, CSB-BFRM analysis could accurately predict clinical responses to more than 90% of drugs approved by the U.S. Food and Drug Administration and more than 75% of experimental clinical drugs that were tested. Mechanistic investigation of OTEs for several high-ranking drug...

Dual Inhibition of the PI3K/mTOR Pathway Increases Tumor Radiosensitivity by Normalizing Tumor Vasculature

Cancer Research — Mon, 02 Jan 2012 05:00:00 +0100

The aberrant vascular architecture of solid tumors results in hypoxia that limits the efficacy of radiotherapy. Vascular normalization using antiangiogenic agents has been proposed as a means to improve radiation therapy by enhancing tumor oxygenation, but only short-lived effects for this strategy have been reported so far. Here, we show that NVP-BEZ235, a dual inhibitor of phosphoinositide-3-kinase (PI3K) and mTOR, can improve tumor oxygenation and vascular structure over a prolonged period that achieves the aim of effective vascular normalization. Because PI3K inhibition can radiosensitize tumor cells themselves, our experimental design explicitly distinguished effects on the blood vasculature versus tumor cells. Drug administration coincident with radiation enhanced the delay in tumor ...

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Apoptosis imaging to monitor cancer therapy: The road to fast treatment evaluation?

Nuklearmedizin — Mon, 02 Jan 2012 05:00:00 +0100

Authors: De Saint-Hubert M, Bauwens M, Verbruggen A, Mottaghy FM Abstract Molecular imaging of biological processes may allow detection of therapy effects before the tumor is reduced in size. The most frequently used PET tracer in oncology, 2-[18F]fluoro-2-deoxyglucose (FDG), suffers from low specificity due to uptake in inflammatory cells. The proliferation marker, 3'-[18F]fluoro-3'-deoxy-L-thymidine (FLT), is less influenced by the inflammatory response following therapy but here disease- and drug-specific effects need to be considered. Since cancer therapy mainly intends to eliminate cancer cells, imaging of cell death offers a direct way to image therapy response. This review gives an overview of the radiopharmaceutical development and in vivo evaluation of radioligands that ha...

Imaging in the age of molecular medicine: Monitoring of anti-angiogenic treatments.

Current Pharmaceutical Biotechnology — Mon, 02 Jan 2012 05:00:00 +0100

Authors: Lederle W, Palmowski M, Kiessling F Abstract Angiogenesis is a complex multistep process and a crucial pre-requisite for tumor growth, invasion and metastasis. A profound knowledge of the mechanisms including the elucidation of markers for angiogenic vessels is essential for the generation of new anti-angiogenic chemotherapeutic agents and the improvement of specific imaging techniques. During the last decades, numerous angiogenesis inhibitors have been developed and some of them have shown promising results in preclinical and clinical trials. However, the response to anti-angiogenic treatment is often delayed and shows high inter-individual variations. In order to improve anti-angiogenic therapy, new specific surrogate markers are necessary that allow the characterization...

[Articles] Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial

The Lancet Oncology — Sun, 01 Jan 2012 05:00:00 +0100

SummaryBackgroundStudies with pertuzumab, a novel anti-HER2 antibody, show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. We investigated the combination of pertuzumab or trastuzumab, or both, with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting.MethodsIn this multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m2, escalating, if tolerated, ...

Test verification and validation for molecular diagnostic assays.

Archives of Pathology and Laboratory Medicine — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Halling KC, Schrijver I, Persons DL Abstract With our ever-increasing understanding of the molecular basis of disease, clinical laboratories are implementing a variety of molecular diagnostic tests to aid in the diagnosis of hereditary disorders, detection and monitoring of cancer, determination of prognosis and guidance for cancer therapy, and detection and monitoring of infectious diseases. Before introducing any new test into the clinical laboratory, the performance characteristics of the assay must be "verified," if it is a US Food and Drug Administration (FDA)-approved or FDA-cleared test, or "validated," if it is a laboratory-developed test. Although guidelines exist for how validation and verification studies may be addressed for molecular assays, the specific detai...

Doxorubicin‐induced activation of NF‐κB in melanoma cells is abrogated by inhibition of IKKβ, but not by a novel IKKα inhibitor

Experimental Dermatology — Sun, 01 Jan 2012 05:00:00 +0100

AbstractDrug resistance is arguably the most important challenge in cancer therapy. Here, doxorubicin induced profound of NF‐κB activation in melanoma cells with a maximum (3.5‐fold) at concentrations relevant in vivo. This was followed by transcriptional induction of several gene products involved in tumor progression. A novel IKKα inhibitor (BAY32‐5915) was identified and characterized, and doxorubicin‐induced NF‐κB activation was assessed following inhibition of IKKα or IKKβ by small‐molecular compounds. While the IKKα inhibitor did not affect doxorubicin‐induced NF‐κB activation, this process was completely abrogated when the IKKβ inhibitor, KINK‐1, was used. Moreover, inhibition of IKKβ, but not IKKα, led to significantly increased apoptosis in response to ...

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Commentary on “Survival after resection for metastatic testicular nonseminomatous germ cell cancer to the lung or mediastinum.” Kenneth A. Kesler,a Laura E. Kruter,a Susan M. Perkins,b Karen M. Rieger,a Katherine J. Sullivan,a Matthew L. Runyan,a John W. Brown,a Lawrence H. Einhorn,caDepartment of Surgery, Cardiothoracic Division and Medicine, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana;bDepartment of Biostatistics, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana;cHematology-Oncology Divisions, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana: Ann Thorac Surg 2011;91:1085–93

Urologic Oncology: Seminars and Original Investigations — Sun, 01 Jan 2012 05:00:00 +0100

Since the advent of cisplatin-based chemotherapy, nonseminomatous germ cell tumors (NSGCT) have been considered one of the most curable solid neoplasms and a model for multimodality cancer therapy. We undertook an institutional review of testicular NSGCT patients who underwent operations to remove lung or mediastinal metastases after chemotherapy in the cisplatin era to determine outcomes. (Source: Urologic Oncology: Seminars and Original Investigations)

Use of bevacizumab in the treatment of metastatic colorectal cancer.

British Journal of Hospital Medicine — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Raouf S, Bridgewater J, Ellis R, Ferry D, Hill M, Wasan H Abstract The Cancer Drugs Fund may allow more patients in England access to clinically effective cancer therapies. In this article oncologists already familiar with the clinical evidence, and experienced in treating with bevacizumab, share practical recommendations on optimal first-line use of this treatment for metastatic colorectal cancer. PMID: 22241406 [PubMed - in process] (Source: British Journal of Hospital Medicine)

Recent progress in targeting cancer.

Aging — Sat, 31 Dec 2011 05:00:00 +0100

Authors: Demidenko ZN, McCubrey JA Abstract In recent years, numerous new targets have been identified and new experimental therapeutics have been developed. Importantly, existing non-cancer drugs found novel use in cancer therapy. And even more importantly, new original therapeutic strategies to increase potency, selectivity and decrease detrimental side effects have been evaluated. Here we review some recent advances in targeting cancer. PMID: 22228887 [PubMed - as supplied by publisher] (Source: Aging)

Dichloroacetic acid up-regulates hepatic glutathione synthesis via the induction of glutamate-cysteine ligase.

Biochemical Pharmacology — Sat, 31 Dec 2011 01:48:04 +0100

Authors: Theodoratos A, Blackburn AC, Cappello J, Tummala P, Dahlstrom JE, Board PG Abstract Dichloroacetic acid (DCA) has potential for use in cancer therapy and the treatment of metabolic acidosis. However, DCA can create a deficiency of glutathione transferase Zeta (GSTZ1-1). Gstz1 knockout mice have elevated oxidative stress and low glutathione levels that increases their sensitivity to acetaminophen toxicity. As it is highly likely that patients that are treated with DCA will develop drug induced GSTZ1-1 deficiency we considered they could be at risk of elevated toxicity if they are exposed to other drugs that cause oxidative stress or consume glutathione (GSH). To test this hypothesis we treated mice with DCA and acetaminophen (APAP). Surprisingly, the mice pre-treated with D...

Ras Regulation of DR5 Expression [Signal Transduction]

Journal of Biological Chemistry — Fri, 30 Dec 2011 05:00:00 +0100

Oncogenic mutations of ras and B-raf frequently occur in many cancer types and are critical for cell transformation and tumorigenesis. Death receptor 5 (DR5) is a cell surface pro-apoptotic death receptor for tumor necrosis factor-related apoptosis-inducing ligand and has been targeted in cancer therapy. The current study has demonstrated induction of DR5 expression by the oncogenic proteins Ras and B-Raf and revealed the underlying mechanisms. We demonstrated that both Ras and B-Raf induce DR5 expression by enforced expression of oncogenic Ras (e.g. H-Ras12V or K-Ras12V) or B-Raf (i.e. V600E) in cells and by analyzing gene expression array data generated from cancer cell lines and from human cancer tissues. This finding is further supported by our results that knockdown of endogenous K-Ra...

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Targeting S100P inhibits colon cancer growth and metastasis by Lentivirus-mediated RNA interference and proteomic analysis.

Molecular Medicine — Thu, 29 Dec 2011 07:24:03 +0100

Authors: Jiang L, Lai YK, Zhang J, Wang H, Lin MC, He ML, Kung HF Abstract S100P was recently found to be overexpressed in a variety of cancers and is considered a potential target for cancer therapy, but the functional role or mechanism of action of S100P in colon cancer is not fully understood. In the present study, we knocked down the gene expression of S100P in colon cancer cells using lentivirus-mediated RNA interference. This step resulted in significant inhibition of cancer cell growth, migration and invasion in vitro and tumor growth and liver metastasis in vivo. Moreover, S100P downstream target proteins were identified by proteomic analysis in colon cancer DLD-1 cells with deletion of S100P. Knockdown of S100P led to downregulation of thioredoxin 1 and β-tubulin and upre...

Swallowing dysfunction in cancer patients

Supportive Care in Cancer — Thu, 29 Dec 2011 06:42:55 +0100

Conclusions Swallowing impairment is a clinically relevant acute and long-term complication in patients with a wide variety of cancers. More prospective studies on the course of dysphagia and impact on quality of life from baseline to long-term follow-up after various treatment modalities, including targeted therapies, are needed. Content Type Journal ArticleCategory Review ArticlePages 1-11DOI 10.1007/s00520-011-1342-2Authors Dysphagia Section, Oral Care Study Group, Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO)Judith E. Raber-Durlacher, Department of Hematology, Leiden University Medical Center, Leiden, the NetherlandsMike T. Brennan, Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC...

Prognostic Proof and Possible Therapeutic Mechanisms of Herbal Medicine in Patients With Metastatic Lung and Colon Cancer

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

Recent studies based on epidemiological models published in this journal and elsewhere have demonstrated encouraging patterns suggesting that herbal treatment may improve prognosis in advanced colon and lung cancer patients. Various problems exist with data from nonrandomized studies of this type, but a strong signal of potential positive effect can be seen. The therapeutic mechanisms of traditional Chinese medicine in metastatic cancer are discussed against a hypothetical, dualistic antiproliferation model and immune-stimulation model of tumor progression and regression. Recommendations are made for a strategy to demonstrate more conclusively the efficacy of adjunct herbal treatment during cancer chemotherapy and for discussions with patients until such time as the efficacy trials are com...

Chemotherapeutic Effects of Bioassay-Guided Extracts of the American Cockroach, Periplaneta americana

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

The organic extract of Periplaneta americana L. (Dictyoptera; Blattidae) has been traditionally used in southwestern China as an alternative medicine against disorders such as hepatitis, trauma, gastric ulcers, burns, and heart disease. The present study describes bioassay-guided purification and chemotherapeutic evaluation of the 60% ethanolic fraction of P americana organic extracts (PAE60). The most effective cytotoxic fraction was determined by way of repeated in vitro screenings against 12 distinct cultured human carcinoma cell lines: Eca 109, BGC823, HO8910, LS174T, CNE, HeLa, K562, PC-3, A549, BEL 7404, HL-60, and KB, followed by in vivo antitumor assays of the lead fraction (PAE60). The complexity of enriched active fraction was qualitatively evaluated using thin layer chromatograp...

A Sad Good-Bye

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

(Source: Integrative Cancer Therapies)

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Altered Circadian Rhythms and Cancer-Related Fatigue Outcomes

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

Fatigue is one of the most frequent and distressing complaints reported by patients with cancer. Describing relationships among disrupted circadian rhythms and cancer-related fatigue is important to the design and testing of interventions that target specific underlying etiology of fatigue. The purpose of this article is to review the literature on whether evidence exists to support the notion that disrupted circadian rhythms provide a mechanism of cancer-related fatigue. Searches were conducted from January 1950 to January 2010, to locate pertinent articles using 4 electronic databases: PubMed, MEDLINE, CINAHL, and Scopus. Results identified 42 quantitative research studies, which were then retrieved. After reviewing the articles, 15 were selected as meeting the established criteria of th...

Is the Improvement of Prognosis of Patients With Metastatic Pulmonary Adenocarcinoma Treated With TCM Herbal Medicine due to Lag Time to Treatment Bias?

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

Conclusion. Increasing lag time to treatment up to 4 months improves the median and 1-year survival of PBT patients without TCM but is unlikely to explain the greatly improved prognosis of PBT + TCM treated patients with fully ambulant stage IV PAC. (Source: Integrative Cancer Therapies)

Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach: Ten-Year Follow-up Data Analyzed With Marginal Structural Models and Propensity Score Methods

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

Although localized colon cancer is often successfully treated with surgery, advanced disease requires aggressive systemic therapy that has lower effectiveness. Approximately 30% to 75% of patients with colon cancer use complementary and alternative medicine (CAM), but there is limited formal evidence of survival efficacy. In a consecutive case series with 10-year follow-up of all colon cancer patients (n = 193) presenting at a San Francisco Bay-Area center for Chinese medicine (Pine Street Clinic, San Anselmo, CA), the authors compared survival in patients choosing short-term treatment lasting the duration of chemotherapy/radiotherapy with those continuing long-term. To put these data into the context of treatment responses seen in conventional medical practice, they also compared survival...

Lung Cancer Survival With Herbal Medicine and Vitamins in a Whole-Systems Approach: Ten-Year Follow-up Data Analyzed With Marginal Structural Models and Propensity Score Methods

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

Complementary and alternative medicines are used by up to 48% of lung cancer patients but have seen little formal assessment of survival efficacy. In this 10-year retrospective survival study, the authors investigated Pan-Asian medicine + vitamins (PAM+V) therapy in a consecutive case series of all non-small-cell lung cancer patients (n = 239) presenting at a San Francisco Bay Area Chinese medicine center (Pine Street Clinic). They compared short-term treatment lasting the duration of chemotherapy/radiotherapy with long-term therapy continuing beyond conventional therapy. They also compared PAM+V plus conventional therapy with conventional therapy alone, using concurrent controls from the Kaiser Permanente Northern California and California Cancer Registries. They adjusted for confounding ...

Beliefs of New Zealand Doctors About Integrative Medicine for Cancer Treatment

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

Conclusion. Integrative medicine is increasingly being accepted in medical practice, although many doctors still do not agree with the use of CAM. There is a need for increased patient–doctor discussions of CAM use. Doctors’ lack of knowledge about CAM may be a barrier to communication and should be addressed with specific medical training. (Source: Integrative Cancer Therapies)

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Elimination of Deleterious Effects of DMBA-Induced Skin Carcinogenesis in Mice by Syzygium cumini Seed Extract

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

The inhibition of tumor incidence by hydro-alcoholic extract of S.cumini seed was evaluated in mice on two stage process of skin carcinogenesis induced by single application of 7, 12-dimethyl benz(a)anthracene (100 µg/100µl of acetone), and 2 weeks later promoted by repeated application of croton oil (1% acetone/thrice in a week) till the end of the experiment (i.e. 16 weeks). Oral administration of extract at a dose of 250mg/kg b.wt./day at the peri-initiational stage (i.e. 7 days before and 7 days after DMBA application), promotional stage (i.e. from the time of croton oil application) and at both the stages (i.e. 7 days prior to DMBA application & continued till the end of experiment) to the mice, recorded a significant reduction in tumor incidence to 37.5, 50 & 25% ...

E-Only Commentaries

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

(Source: Integrative Cancer Therapies)

Errata

Integrative Cancer Therapies — Thu, 29 Dec 2011 05:00:00 +0100

Li Y, Yue H, Xing Y, Sun H, Pan Z, and Xie G. Oxymatrine Inhibits development of morphine-induced tolerance associated with decreased expression of P-glycoprotein in rats. Integrative Cancer Therapies. 2010.9(2): 213-218. Original DOI: 10.1177/1534735410369671 (Source: Integrative Cancer Therapies)

Polysaccharide-K (PSK) in Cancer - Old Story, New Possibilities?

Current Medicinal Chemistry — Thu, 29 Dec 2011 05:00:00 +0100

Authors: Sun C, Rosendahl AH, Wang XD, Wu DQ, Andersson R Abstract Polysaccharide-K (PSK, Krestin) is one of the most commonly used medicinal mushroom extracts with a long history as an additive in cancer therapy in Asia, especially in Japan. PSK has a documented anti-tumor activity both in vitro and in vitro, in various types of cancers, including colorectal, gastric, breast, liver, pancreatic, and lung cancer. Despite PSK having been studied for about 40 years as an immune modulator and biological response modifier, the mechanisms of action by PSK have not yet been clearly and completely elucidated. This review aims to provide an up-to-date account for the effects of PSK in cancer with the hope of thereby providing an increased understanding of the molecular mechanisms of PSK and...

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Mitochondrial VDAC1: Function in Cell Life and Death and a Target for Cancer Therapy.

Current Medicinal Chemistry — Thu, 29 Dec 2011 05:00:00 +0100

Authors: Shoshan-Barmatz V, Golan M Abstract Found at the outer mitochondrial membrane, the voltage-dependent anion channel, VDAC, assumes a crucial position in the cell, serving as the main interface between mitochondrial and cellular metabolisms by mediating transport of ions and metabolites. VDAC thus functions as a gatekeeper, controlling cross-talk between mitochondria and the rest of the cell. Moreover, its location at the boundary between the mitochondria and the cytosol enables VDAC to interact with proteins that mediate and regulate the integration of mitochondrial functions with other cellular activities. Here, we review current knowledge related to the roles played by VDAC in the regulation of cell life and cell death, with relation to cancer. The current concepts of alt...

Multi-Targeted Histone Deacetylase Inhibitors in Cancer Therapy.

Current Medicinal Chemistry — Thu, 29 Dec 2011 05:00:00 +0100

Authors: Ai T, Cui H, Chen L Abstract The heterogeneous nature of cancer requires a comprehensive approach for attacking the multiple mechanisms underlying the initiation and progression of cancers. Histone deacetylase inhibitors (HDACi) have emerged as a new class of anticancer agents, targeting the biological processes including cell cycle, apoptosis and differentiation. Studies have revealed that HDACi are synergistic with diverse classes of anticancer therapies including targeted therapeutics and conventional anticancer agents. Extensive medicinal chemistry efforts have yielded a wide range of chemical structures, indicative of the structural flexibility of HDACi. These findings have supported a strategy to generate multi-targeted HDACi by combining structural features from HDA...

RNA Interference-Mediated Validation of Survivin and Apollon/BRUCE as New Therapeutic Targets for Cancer Therapy.

Current Topics in Medicinal Chemistry — Thu, 29 Dec 2011 03:48:22 +0100

Authors: Pennati M, Millo E, Gandellini P, Folini M, Zaffaroni N Abstract The ability to evade apoptosis is one of the defining hallmarks of cancer. It enables the survival of cancer cells under abnormal growth stimulation and mediates their increased resistance to treatment with cytotoxic drugs and radiation. Therefore, antiapoptotic proteins that counteract apoptosis signaling represent promising new therapeutic targets to impair cancer cell growth and enhance treatment response. As soon as RNA interference (RNAi) was demonstrated in mammalian cells, it rapidly became an essential tool for gene knockdown in preclinical models, making it possible to define the role of specific genes in the onset and progression of cancer and explore their potential as therapeutic targets. The pres...

Bay846, a new irreversible small molecule inhibitor of EGFR and Her2, is highly effective against malignant brain tumor models

Investigational New Drugs — Wed, 28 Dec 2011 06:53:28 +0100

Summary The epidermal growth factor receptor (EGFR) pathway is aberrantly activated in tumors and plays a key role in promoting tumor growth. Small molecule inhibitors which bind reversibly to EGFR have demonstrated limited clinical activity. Thus, there is a continued need to develop novel EGFR inhibitors with improved anti-tumor activity. Bay846 is a newly developed small molecule inhibitor that binds irreversibly to the tyrosine kinase domains of EGFR and Her2. The in vitro and in vivo efficacy of Bay846 was tested using a panel of nine human malignant brain tumor (glioma) models. Lapatinib, a reversible inhibitor of EGFR and Her2, was included for comparison. Six glioma cell lines were sensitive to Bay846 treatment. Bay846 strongly suppressed tumor cell growth in vitro ...

Silibinin suppresses the maintenance of colorectal cancer stem‐like cells by inhibiting PP2A/AKT/mTOR pathways

Journal of Cellular Biochemistry — Wed, 28 Dec 2011 05:00:00 +0100

This study aimed to examine whether silibinin inhibited the development of CSLCs and disclose the underlying signaling. The colorectal cancer spheroid culture system was used for enriching CSLCs. The effects of silibinin on CSLCs were evaluated by counting sphere numbers, and calculating the percentage of CD133+ cells by flow cytometry and immunofluorescence both in the absence and presence of different concentrations of silibinin. The results showed the sphere number of CCS was 36 ± 9.6 after 15 days of CSLC enrichment in spheroid culture, and the percentage of CD133+ cells increased to 18 ± 6.4% compared to 3 ± 0.8% before enrichment. Treatment with silibinin reduced the sphere formation to 5 ± 3.3 and decreased the CD133+ percentage to 8 ± 2.3%. Interestingly, t...

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Oxidative DNA damage repair

ScienceDaily Headlines — Tue, 27 Dec 2011 20:37:37 +0100

Oxidative stress damages DNA. Researchers have now decoded the mechanism that repairs DNA damaged in this way. This repair mechanism could lead to less invasive approaches in cancer therapy and contribute to the development of new tests for the early diagnosis of cancer. (Source: ScienceDaily Headlines)

Synergistic inhibition of hepatocellular carcinoma growth by cotargeting chromatin modifying enzymes and poly (ADP‐ribose) polymerases

Hepatology — Tue, 27 Dec 2011 05:00:00 +0100

Conclusion: These findings suggest that combination therapy with both enzyme inhibitors may be a strategy for therapy of sensitive HCC cells, and identification of these novel molecular determinants may eventually guide the optimal use of PARP and HDAC inhibitors in the clinic. (HEPATOLOGY 2011.) (Source: Hepatology)

Best Case Series Program Supportive Cases of Cordyceps militaris- and Panax notoginseng-Based Anticancer Herbal Formula

Integrative Cancer Therapies — Tue, 27 Dec 2011 05:00:00 +0100

Conclusion. C militaris and P notoginseng are potential anticancer herbal prescriptions for adenocarcinoma and mucosa-associated lymphatic tissue type lymphoma. (Source: Integrative Cancer Therapies)