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Postoperative radiotherapy after radical prostatectomy: adjuvant or salvage?
Scott C. Morgan and Chris C. Parker
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00002]


Topical Chemoprevention of Skin Cancers with Phytochemicals
Lining Feng, Mary C. Zoccoli and Zhi Wang
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00005]


Advances in the management of brain tumors in infants
Luca Massimi, Benedetta Pettorini, Gianpiero Tamburrini, Massimo Caldarelli and Concezio Di Rocco
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00013]


THE OPTIMAL DIAGNOSIS OF UROTHELIAL CARCINOMA OF THE BLADDER
Alan M. Nieder, Jeetu Nebhnani and Fernando J. Bianco
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00018]


microRNAs, Gap Junctional Intercellular Communication and Mesenchymal Stem Cells in Breast Cancer Metastasis
Larissa A. Gregory, Rachel A. Ricart, Shyam A. Patel, Philip K. Lim and Pranela Rameshwar
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00019]


Contemporary role of endocrine treatment in patients with localized or locally advanced prostate cancer. A review
Vallejo Herrador J and Martínez-Piñeiro L
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00021]


Targeting lentiviral vectors for cancer immunotherapy
Frederick Arce, Karine Breckpot, Mary Collins and David Escors
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00022]


Induction of antitumor immune responses with recombinant lentivector: Role of skin derived DCs
Qifeng Zhou and Yukai He
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00023]


The optimal diagnosis of urothelial carcinoma of the bladder
Alan M. Nieder, Jeetu Nebhnani and Fernando J. Bianco
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00024]


Complete Manuscript Title:  Breast reconstruction – a historical perspective on available techniques for patients electing bilateral mastectomy
Jonas A. Nelson,  Julia Tchou, Susan Domchek, David W. Low, Joseph M. Serletti  and Liza C. Wu
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00025]


Anti-VEGF and Anti-EGFR Monoclonal Antibodies in the First-line Therapy for Metastatic Colorectal Cancer - A Meta-Analysis
Zheng Zhou, William V. Walsh, Venu G. Bathini and Bilal Piperdi
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00026]


The cross-over of anticancer agents with osteoclast activities
Henning M. Schramm
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00027]


Radiation Therapy in the Early 21st Century: Technological Advances
Milad Enferadi , Mahdi Sadeghi  and Alireza Shirazi
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00028]


Adrenergic action in breast cancer
Isabel Alicia Lüthy, Ariana Bruzzone and Cecilia Pérez Piñero
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00029]


The adrenergic system in gastrointestinal cancers
Zhi Jie Li and Chi Hin Cho
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00030]


Beta-adrenergic signaling in the development and progression of pulmonary and pancreatic adenocarcinoma
Hildegard M. Schuller and Hussein A. N. Al-Wadei
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00031]


Acoustic Radiation Force Impulse (ARFI) Imaging: a Review
Kathryn Nightingale
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00032]


Stress related neuroendocrine influences in ovarian cancer
Yu Kang, Susan K. Lutgendorf, Wei Hu, Steven W. Cole and Anil K. Sood
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00033]


Sympathetic signaling in angiogenesis: implications for cancer progression
Jason Tilan, Magdalena Czarnecka and Joanna Kitlinska
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00034]



Abstracts



Postoperative radiotherapy after radical prostatectomy: adjuvant or salvage?
Scott C. Morgan and Chris C. Parker
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00002]

Adverse pathologic features – including positive surgical margins, extracapsular extension, and seminal vesicle invasion – are common findings at radical prostatectomy for clinically localised disease. In the absence of further treatment, patients with such features are at high risk of biochemical and local recurrence and the development of metastatic disease. Radiotherapy is the only known curative treatment modality in patients with locally recurrent disease. Its optimal use following surgery, however, is controversial. In this review, the evidence for immediate (adjuvant) and selective early salvage approaches to postoperative radiotherapy are presented. The results of three randomized controlled trials comparing adjuvant radiotherapy to observation are discussed. The trial with the longest follow-up now demonstrates that, compared to a policy of observation, adjuvant radiotherapy prolongs overall survival and prevents distant metastases. It is not clear, however, whether this survival advantage would remain if adjuvant radiotherapy were compared to a strategy of close monitoring with salvage radiotherapy instituted at the time of biochemical failure. A selective salvage strategy has the advantage of avoiding ‘unnecessary’ radiotherapy, and its toxicity, for those patients destined not to fail after surgery. Large-scale randomized controlled trials comparing these two approaches are underway.
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Topical Chemoprevention of Skin Cancers with Phytochemicals
Lining Feng, Mary C. Zoccoli and Zhi Wang
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00005]

Skin cancer is the most common malignancy. Its pathogenesis is a multi-step, cumulative process which allows for potential intervention along the length of its spectrum. Cancer chemoprevention is a very promising approach to obtaining this goal. Unfortunately, its widespread application in clinic has been hampered by several problems, including systemic side effects especially if the medication requires prolonged use. For this reason, possible alternative measures have been investigated and are of great interest. The application of phytochemicals and other natural compounds is an appealing approach in that they are generally nontoxic, less costly and widely available. Topical application (e.g., transdermal systems, painting) of chemopreventives also serves as an alternative to systemic administration, and may limit side effects without sacrificing clinical advantages. The purpose of this paper is to provide an extensive investigation of the literature regarding current chemopreventative practices. This paper focuses discussions on the topical application of phytochemicals, by representing recent studies and findings. Based on recognition amongst the literature, five compounds are represented which include resveratrol, green tea, perillyl alcohol, ginger and inositol hexaphosphate. More compounds are also named with brief introduction, and further study is discussed.
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Advances in the management of brain tumors in infants
Luca Massimi, Benedetta Pettorini, Gianpiero Tamburrini, Massimo Caldarelli and Concezio Di Rocco
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00013]

The last two decades have been crucial  for neurooncology due to the enormous progress in the base research and in the medical technology. Such a continuous development has significantly improved the knowledge on the genetics and molecular biology of brain tumors, thus allowing to better define their prognosis and to find new therapeutic targets. Furthermore, it has provided sophisticated diagnostic and therapeutic tools that have radically changed the behavior of neurosurgeons, neurooncologists, and radiotherapists with regards to these neoplasms.

Once considered rare and poorly treatable, infantile brain tumors (IBTs) are currently more and more diagnosed and benefit of the aforementioned progresses so that their prognosis  has become quite similar to that of the older ages. The aim of the present paper is to review the factors that favored these advances and to analyze the main aspects concerning IBTs, namely:

• Current information on epidemiology and etiology;
• Advances in the neuroimaging;
• Changes in the surgical attitude;
• Development of ad hoc chemotherapic and radiotherapic protocols;
• The role of pathology and molecular biology in the prognosis;
• Outcome;
• Future directions.

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THE OPTIMAL DIAGNOSIS OF UROTHELIAL CARCINOMA OF THE BLADDER
Alan M. Nieder, Jeetu Nebhnani and Fernando J. Bianco
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00018]

Urothelial cancer (UC) of the bladder is a relatively common disease seen in Americans, especially those who have significant tobacco exposure history.  While the signs and symptoms of UC can be relatively straight-forward (e.g., hematuria, irritative voiding symptoms), a complete work-up is required to appropriately stage each patient.  The work-up of UC consists of: a high level of suspicion for patients with hematuria to prevent missed or delayed diagnoses; an exam under anesthesia; imaging studies; urinary markers and cytology; cystoscopy and transurethral resection of the bladder tumor (TURBT), as well as potential repeat TURBT to prevent understaging and residual disease. 
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microRNAs, Gap Junctional Intercellular Communication and Mesenchymal Stem Cells in Breast Cancer Metastasis
Larissa A. Gregory, Rachel A. Ricart, Shyam A. Patel, Philip K. Lim and Pranela Rameshwar
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00019]

The failed outcome of autologous bone marrow transplantation for breast cancer opens the field for investigations. This is particularly important because the bone marrow could be a major source of cancer cells during tertiary metastasis. This review discusses subsets of breast cancer cells, including those that enter the bone marrow at an early period of disease development, perhaps prior to clinical detection. This population of cells evades chemotherapeutic damage even at high doses. An understanding of this population might be crucial for the success of bone marrow transplants for metastatic breast cancer and for the eradication of cancer cells in bone marrow. In vivo and in vitro studies have demonstrated gap junctional intercellular communication (GJIC) between bone marrow stroma and breast cancer cells. This review discusses GJIC in cancer metastasis, facilitating roles of mesenchymal stem cells (MSCs). In addition, the review addresses potential roles for miRNAs, including those already linked to cancer biology. The literature on MSCs is growing and their links to metastasis are beginning to be significant leads for the development of new drug targets for breast cancer. In summary, this review discusses interactions among GJIC, miRNAs and MSCs as future consideration for the development of cancer therapies.
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Contemporary role of endocrine treatment in patients with localized or locally advanced prostate cancer. A review
Vallejo Herrador J and Martínez-Piñeiro L
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00021]

The objetive of this paper is to undertake a review of hormone therapy in localized or locally advanced prostate cancer. We have searched MEDLINE (1996-2009) for randomized or quasi- randomized controlled trials of patients with localised or locally advanced prostate cancer, that is, stages T1-T4, any N, M0, analizing:

1. Primary hormone therapy alone
2. Neoadjuvant hormone therapy plus prostatectomy
3. Neoadjuvant +/- concomitant hormone therapy plus radiotherapy
4. Neoadjuvant hormone therapy plus radiotherapy plus adjuvant hormone therapy
5. Adjuvant hormone therapy to primary curative intent.
1. Radical prostatectomy and adjuvant hormone therapy
2. Radiotherapy and adjuvant hormone therapy
3. Adjuvant hormone therapy with bicalutamide
4. Duration of adjuvant hormone therapy to  radiotherapy
6. Early vs deferred hormonal treatment
7. Hormone therapy and brachyterapy or cryotherapy
   

Until very recently it was known that endocrine therapy could improve progression free survival but few studies could demostrate a survival advantage in patients treated wih early endocrine therapy.

Treatment of locally advanced prostate cancer (T3-4 N0 M0, T1-4 N1 M0) just with early androgen deprivation has shown not to be superior to deferred androgen deprivation in terms of neither overall nor prostate cancer specific survival. In locally advanced prostate cancer in order to gain benefit of early androgen deprivation, either radical prostatectomy or radiotherapy must be added.

Results of several randomized and non-randomized clinical trials published in the English literature suggest that neo-adjuvant hormone therapy prior to prostatectomy does not improve overall survival. The use of longer duration of neo-adjuvant hormone therapy has any impact in patients survival. Patients treated with radiotherapy show a different outcome. Neo-adjuvant hormones prior to radiotherapy significantly improves both clinical disease-free survival and overall survival at 5 and 10 years.
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Targeting lentiviral vectors for cancer immunotherapy
Frederick Arce, Karine Breckpot, Mary Collins and David Escors
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00022]

Delivery of tumour-associated antigens (TAA) in a way that induces effective, specific immunity is a challenge in anti-cancer vaccine design. Circumventing tumour-induced tolerogenic mechanisms in vivo is also critical for effective immunotherapy. Effective immune responses are induced by professional antigen presenting cells, in particular dendritic cells (DC). This requires presentation of the antigen to both CD4⁺ and CD8⁺ T cells in the context of strong co-stimulatory signals. Lentiviral vectors have been tested as vehicles, for both ex vivo and in vivo delivery of TAA and/or activation signals to DC, and have been demonstrated to induce potent T cell mediated immune responses that can control tumour growth. This review will focus on the use of lentiviral vectors for in vivo gene delivery to DC, introducing strategies to target DC, either targeting cell entry or gene expression to improve safety of the lentiviral vaccine or targeting dendritic cell activation pathways to enhance performance of the lentiviral vaccine. In conclusion, this review highlights the potential of lentiviral vectors as a generally applicable ‘off-the-shelf’ anti-cancer immunotherapeutic.
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Induction of antitumor immune responses with recombinant lentivector: Role of skin derived DCs
Qifeng Zhou and Yukai He
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00023]

T cell immune responses play a critical role in preventing and treating malignant tumors.
The most effective way for stimulating potent T cell immunity is by genetic immunization with
recombinant viral vectors. Recombinant lentivector has recently been studied as antigen
delivery vehicle for stimulating potent T cell responses. Studies showed that lentivector
immunization can induce remarkably potent and durable CD8 T cell responses possibly
because of their high efficiency of transducing dendritic cells (DCs) and persistent Antigen
presentation. In this brief review, we summarized the recent findings on the basic mechanistic
studies, especially on the role of DC subsets in lentivector immunization, and the potential
applications of using lentivector immunization for tumor immunotherapy in preclinical animal models.
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The optimal diagnosis of urothelial carcinoma of the bladder
Alan M. Nieder, Jeetu Nebhnani and Fernando J. Bianco
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00024]

Urothelial cancer (UC) of the bladder is a relatively common disease seen in Americans, especially those who have significant tobacco exposure history.  While the signs and symptoms of UC can be relatively straight-forward (e.g., hematuria, irritative voiding symptoms), a complete work-up is required to appropriately stage each patient.  The work-up of UC consists of: a high level of suspicion for patients with hematuria to prevent missed or delayed diagnoses; an exam under anesthesia; imaging studies; urinary markers and cytology; cystoscopy and transurethral resection of the bladder tumor (TURBT), as well as potential repeat TURBT to prevent understaging and residual disease.
[Back to top]


Complete Manuscript Title:  Breast reconstruction – a historical perspective on available techniques for patients electing bilateral mastectomy
Jonas A. Nelson,  Julia Tchou, Susan Domchek, David W. Low, Joseph M. Serletti  and Liza C. Wu
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00025]

Studies have shown that breast conserving surgery is as efficacious as mastectomy in the treatment of women with early stage breast cancer.  Recent publications, however, have demonstrated an increasing number of women electing bilateral mastectomy when diagnosed with unilateral breast cancer.   Several plausible reasons for this rising trend for bilateral mastectomy include increased awareness of breast cancer risk in the contralateral breast, increased use of breast MRI as a diagnostic tool and advances in reconstructive and mastectomy techniques.  This review will focus mainly on the reconstructive options within the third probable reason for the increasing trend of bilateral mastectomy, advances in breast reconstruction and mastectomy techniques.   The various options in breast reconstruction will be presented with a historical perspective, as well as a brief discussion on current mastectomy techniques in breast surgical oncology, as advances in both fields have likely influenced the rising trend of bilateral mastectomy in the United States.
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Anti-VEGF and Anti-EGFR Monoclonal Antibodies in the First-line Therapy for Metastatic Colorectal Cancer - A Meta-Analysis
Zheng Zhou, William V. Walsh, Venu G. Bathini and Bilal Piperdi
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00026]

Introduction: The optimal Anti-VEGF (vascular endothelial growth factor) and Anti-EGFR (epithelial growth factor receptor) antibody regimen to combine with chemotherapy in the first-line treatment for metastatic colorectal cancer remains to be better defined. Results from randomized controlled trials are variable.

Methods: A meta-analysis was performed by searching PubMed, Cochrane Registry, major oncology conferences proceedings until February 2010 for randomized controlled trials of Anti-VEGF and Anti-EGFR in first-line treatment of metastatic colorectal cancer. Summary estimates of progression-free survival, overall survival, overall response rate and 60-day mortality were derived. Effect of k-ras status was stratified in trials involving Anti-EGFR.

Results: Nine trials were included, including three anti-VEGF +/- chemotherapy, n=2422; four anti-EGFR +/- chemotherapy, n=4348 and two anti-VEGF with chemotherapy +/- anti-EGFR, n=1601. Adding anti-VEGF to chemotherapy showed a 20-30% risk reduction in disease progression and mortality, and a higher response rate. Benefit of anti-EGFR was seen only in k-ras wild type patients with 20% reduction in disease progression and 10% reduction of mortality. Adding both antibodies to chemotherapy showed worse survival outcomes.

Conclusion: Benefit of adding anti-VEGF in first-line metastatic colorectal cancer treatment is well pronounced. Combing anti-EGFR with chemotherapy showed significant increase in response rate and PFS in k-ras wild type patients. Adding both antibodies to chemotherapy appeared inferior regardless of k-ras status.
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The cross-over of anticancer agents with osteoclast activities
Henning M. Schramm
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00027]

Bone loss and increased risk of fractures often result from treatment with antitumoral agents due to more or less severe reduction of bone remodeling. Although various anticancer treatments reduce or inhibit osteoclast activities, the balance of bone remodeling is usually not biased towards osteoblast activity. The activity of osteoclasts is coupled with the activity of osteoblasts. Consequently, inhibition of osteoclast activity often implies reduction of osteoblast activity as well, or vice versa. Depending on the antitumoral substance used, there are large differences in the actions of antitumoral substances on this balancing effect. The less broad the antiproliferative properties of anticancer agents are, and the more they act in a targeted way, the more they show specific effects on both osteoclasts and osteoblasts.

However, osteopenia and osteoporosis common in cancer patients is not caused solely by the anticancer treatment. Metastasizing cancer cells in the bone may provoke increased osteoclastogenesis and disturb the bone remodeling balance.  Moreover, cancer patients with localized squamous-cell head and neck cancer already show increased bone resorption and decreased bone mass independently of treatment, and smoking or drinking habits. And even carcinogenesis in the intestine and other sites can be prevented by antirheumatic substances that inhibit osteoclastogenesis and have an anti-inflammatory action.

The question thus arises as to how bone remodeling and cancer development are related. Is the anti-osteoclastic activity of antitumoral agents involved in the prevention of carcinogenesis, and part of the antitumoral activity? This review demonstrates that osteoclastogenesis and cancer may be related in a complex manner. Experimental studies suggest that anticancer agents exert their activity by inhibiting the signaling pathways commonly over-expressed in cancer cells, as well as in cells responsible for bone remodeling.
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Radiation Therapy in the Early 21st Century: Technological Advances
Milad Enferadi , Mahdi Sadeghi  and Alireza Shirazi
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00028]

Background: Today, cancer treatment is one of challenges in health and treatment system of any country. With quick development of radiation therapy and chemotherapy in recent years, this question is brought up that which method is more perfect to treat cancer.

Methods: Radiation therapy is consisted of several methods including external radiation therapy (e.g. CyberKnife, IMRT, IGRT, SBRT, BNCT, Vero, IORT, Gamma knife, Tomotherapy and Volumetric modulated arc therapy (VMAT)) and internal radiation therapy (e.g. brachytherapy, endoradiotherapy (target radionuclide therapy): radioimmunotherapy and peptide receptor radionuclide therapy) that any one has a special function in cancerous cells destroy.

Results: Chemotherapy has still its place in cancer treatment and is used as a current and worldwide method. Nowadays, radiation therapy evolves with a surprising growth. By abandoning Cobalt-60, linear and circular accelerators which are able to accelerate particles, could be used for cancer treatment. CyberKnife, IMRT, IGRT, SBRT, VMAT, tomotherapy and Vero are the most advanced methods used to radiation therapy in all angles which had minimum mistake in radiation to the near intact tissues. Today, brachytherapy by increasing production of treatment radioisotopes by cyclotron and reactor is used in the world. Endoradiotherapy (Target radionuclide therapy): Radioimmunotherapy and peptide-receptor radionuclide therapy are two considerable methods in cancer treatment.

Conclusion: In this review, we consider principals and application of radiation therapy in the early 21st century.
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Adrenergic action in breast cancer
Isabel Alicia Lüthy, Ariana Bruzzone and Cecilia Pérez Piñero
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00029]

Breast cancer is the most frequent malignancy in women in the majority of western countries. Both acute and chronic stress cause the release of epinephrine and norepinephrine. These natural cateholamines bind to nine different adrenoceptors. Breast cancer epithelial cells express α₂ and β₂-adrenoceptors. Catecholamine binding to α₂-adrenoceptors in cancer cells is associated with increased cell proliferation. On the contrary, catecholamine binding to β₂-adreno­ceptors result in diminished cell proliferation. Therefore, the relative concentration of these receptors in the tumor cell will enhance or diminish proliferation. Also in vivo, following stimulation with natural catecholamines, the tumor will experience enhanced or diminished growth depending on the relative concentration of α₂ and β₂-adrenoceptors. The administration of synthetic α₂-adrenergic agonists enhances tumor growth whereas the administration of the α₂-adrenergic antagonist rauwolscine dimi­ni­shes tumor growth below control levels, behaving as an inverse agonist. The adminis­tra­tion of β-adrenergic agonists could also be useful to lower tumor growth. The use of β-blockers in patients have been described by several groups as very promising specially in the case of the HER2 positive and triple negative tumors. Thus different therapeutic compounds targeting adrenergic receptors could become very important drugs for the treatment of selected cancer patients. Currently, adrenergic agonists/antagonists are used for the treatment of different diseases and have minimal side effects when compared with chemotherapy. The possibility of using them for treatment of breast cancer is an encouraging concept especially for the patients with resistance to the usual anti-cancer therapy.
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The adrenergic system in gastrointestinal cancers
Zhi Jie Li and Chi Hin Cho
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00030]

It has been demonstrated by clinical and animal studies that stress stimulation plays a pivotal role in the tumor development and progression. Adrenergic system activation mediates most of the effects resulting from stress stimulation. Various cigarette components have been indicated for inducing the secretion of stress hormones such as noradrenaline and adrenaline which activate the adrenoceptors expressed on tumor cells and initiate different biological effects. Gastrointestinal (GI) cancers, a common malignancy in the body are also influenced by stress stimulation to a great extent. Combined stress stimulation with cigarette smoking can further accelerate tumor progression, and even develop chemoresistance in cancer cells. Therefore the involvement of adrenoceptors in these biological processes and habitual behaviours are becoming interesting therapeutic targets. Indeed various adrenoceptor blockers are implicated as promising therapeutic agents to prevent and treat relevant cancers including those in the GI tract. In this review, we sum up the possible relationship between the adrenergic system and GI cancers and provide a mechanistic understanding on this relationship. Meanwhile, we also further discuss the role of cigarette smoke and its active ingredient nicotine which is highly associated with the adrenergic system in the development of GI cancers.
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Beta-adrenergic signaling in the development and progression of pulmonary and pancreatic adenocarcinoma
Hildegard M. Schuller and Hussein A. N. Al-Wadei
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00031]

Small airway epithelial cells from, which most pulmonary adenocarcinomas (PACs) derive, and pancreatic duct epithelia, from which pancreatic ductal adenocarcinomas (PDACs) originate, share the ability to synthesize and release bicarbonate. This activity is stimulated in both cell types by the a7nicotinic acetylcholine receptor (α7nAChR)-mediated release of noradrenaline and adrenaline, which in turn activate b-adrenergic receptor (β-AR) signaling, leading to the cAMP-dependent release of bicarbonate. The same signaling pathway also stimulates a complex network of intracellular signaling cascades which regulate the proliferation, migration, angiogenesis and apoptosis of PAC and PDAC cells. The amino acid neurotransmitter γ-aminobutyric acid (GABA) serves as the physiological inhibitor of this cancer stimulating network by blocking the activation of adenylyl cyclase. This review summarizes experimental, epidemiological and clinical data that have identified risk factors for PAC and PDAC such as smoking, alcoholism, chronic non neoplastic diseases and their treatments as well as psychological stress and analyzes how these factors increase the cancer-stimulating effects of this regulatory cascade in PAC and PDAC. This analysis identifies the careful maintenance of balanced levels in stimulatory stress neurotransmitters and inhibitory GABA as a key factor for the prevention of PDAC and suggests the marker-guided use of beta-blockers, GABA or GABA-B receptor agonists  as well as psychotherapeutic or pharmacological stress reduction as important tools that may render currently ineffective cancer intervention of PAC and PDAC more successful.
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Acoustic Radiation Force Impulse (ARFI) Imaging: a Review
Kathryn Nightingale
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00032]

Acoustic radiation force based elasticity imaging methods are under investigation by many groups.  These methods differ from traditional ultrasonic elasticity imaging methods in that they do not require compression of the transducer, and are thus expected to be less operator dependent.  Methods have been developed that utilize impulsive (i.e.< 1 ms), harmonic (pulsed), and steady state radiation force excitations.  The work discussed in this paper utilizes impulsive methods, for which two imaging approaches have been pursued: 1) monitoring the tissue response within the radiation force region of excitation (ROE) and generating images of relative differences in tissue stiffness (Acoustic Radiation Force Impulse (ARFI) imaging); and 2) monitoring the speed of shear wave propagation away from the ROE to quantify tissue stiffness (Shear Wave Elasticity Imaging (SWEI)).  For these methods, a single ultrasound transducer on a commercial ultrasound system can be used to both generate acoustic radiation force in tissue, and to monitor the tissue displacement response.  The response of tissue to this transient excitation is complicated and depends upon tissue geometry, radiation force field geometry, and tissue mechanical and acoustic properties.  Higher shear wave speeds and smaller displacements are associated with stiffer tissues, and slower shear wave speeds and larger displacements occur with more compliant tissues.  ARFI images have spatial resolution comparable to that of B-mode, often with greater contrast, providing matched, adjunctive information.  SWEI images provide quantitative information about the tissue stiffness, typically with lower spatial resolution.  A review these methods and examples of clinical applications are presented herein.
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Stress related neuroendocrine influences in ovarian cancer
Yu Kang, Susan K. Lutgendorf, Wei Hu, Steven W. Cole and Anil K. Sood
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00033]

A growing body of epidemiologic and clinical evidence points to a significant role of biobehavioral and associated neuroendocrine factors on cancer growth and progression. This review provides an overview of the emerging relationships between neuroendocrine pathways and ovarian cancer progression. The primary focus of this review is on the contributions of neuroendocrine influences on cancer cell biology and tumor microenvironment in ovarian cancer. This mechanistic understanding will inform new opportunities for pharmacological and behavioral interventions for improving the outcome of ovarian cancer patients.
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Sympathetic signaling in angiogenesis: implications for cancer progression
Jason Tilan, Magdalena Czarnecka and Joanna Kitlinska
[FULL-TEXT INQUIRY] [BSP/CCTR/E-Pub/00034]

Sympathetic neurotransmitters are known for their multiple and pleiotropic functions. Recently, regulation of tumor angiogenesis emerged as one of them. Norepinepherine and epinephrine have been shown to stimulate tumor vascularization via two independent mechanisms – induction of growth factor release from tumor and stromal cells, and a direct effect on endothelial cell (EC) proliferation. In contrast, their precursor, dopamine, interferes with vascular endothelial growth factor (VEGF) signaling in ECs and inhibits angiogenesis. Tumor vascularization can be also regulated by peptidergic neurotransmitters, such as neuropeptide Y (NPY), which acts as a potent angiogenic factor due to its direct stimulatory effect on EC proliferation, migration and capillary formation. The angiogenic activity of these neuronal factors is particularly apparent under the conditions of increased sympathetic activity during stress, or in tumors of sympathetic origin. However, there is also evidence indicating that basal sympathetic activity is essential for sustained growth of non-neuronal tumors. Importantly, sympathetic activity increases in hypoxia, which is a crucial factor inducing neovascularization. Moreover, in tumor cells, adrenergic stimulation up-regulates hypoxia-inducible factor 1α (HIF-1α) independently on oxygen levels, which mimics hypoxic conditions and increases the release of angiogenic factors. The pro- and anti-angiogenic effects of sympathetic neurotransmitters are potent enough to alter rates of tumor growth and metastases, confirming their potential value as therapeutic targets. However, such therapy may be complicated by other activities of these neuronal factors, such as immunomodulation and direct effects on tumor cell functions, which are tumor specific and may both facilitate and inhibit tumor growth.
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