Marina A Guvakova completed her PhD in Cell Biology at Russian Academy of Sciences and Post-doctoral training at Columbia and Thomas Jefferson University, USA.She is an Assistant Professor at University of Pennsylvania Perelman School of Medicine and a Senior Research Investigator in Department of Surgery. She is an author of 20+ papers, recipient of New Investigator Award from Endocrine Society, Breast Cancer Research Award from DoD BCRP and Gordon Research Conferences Awards. She serves as a Reviewer for several journals, Editorial Board Member of ISRN Endocrinology and a CDMRP peer-review panel member.

Background: A subset of patients with ductal carcinoma in situ (DCIS) will develop invasive breast cancer (IBC). To date, there are no predictive biomarkers for identifying this subset with worse prognosis because progressive cancers in situ (CIS) are essentially indistinguishable histologically from those with favorable outcomes.We hypothesized that the measurable parameters discriminating CIS from CIS with concurrent microinvasion may serve as early diagnostic biomarkers (BM) of cancer progression.

Methods: Using a novel imaging-based method, we measured the relative expression levels of proteins implicated in cancer progression- the insulin-like growth factor I receptor (IGF-IR), Ras-related protein 1 (Rap1), and Vav2 oncoprotein. Protein profiles were compared in 42 histologically normal mammary samples, 71 CIS (35 without/36 with invasion either on diagnostic biopsy or final surgical excision), and 98 IBC of known estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status.

Results: The levels of the IGF-IR and Rap1 protein expression were significantly elevated in ER-positive (ER+/PR+/-/HER2–) DCIS relative to normal epithelium (P<0.0001). The IGF-IR protein expression was also significantly up regulated in HER2-positive (ER+/-/PR+/-/HER2+) DCIS relative to normal epithelium (P=0.0002). IGF-IR and Rap1 protein expression levels were similar among DCIS patients without or with concurrent invasion. Vav2 upregulation in DCIS relative to normal group was not associated with steroid hormone receptor and HER2 status, but was associated with the presence of concurrent invasion. DCIS with high Vav2 were more than twice as likely to progress to invasive cancers as DCIS with low Vav2 (odds ratio, 2.42; 95% CI, 1.26-4-65; P=0.008). Furthermore, a receiver operating characteristic curve analysis revealed moderate ability of Vav2 protein expression measurements in DCIS to predict the existence of invasion concurrent with DCIS (area under the curve, 0.71; 95% CI, 0.59-0.84).

Conclusions: Our novel findings hold promise for utilizing Vav2 as a predictive BM for differentiating progressive from nonprogressive DCIS.

Acute myeloid leukemia is typically a disease of the older population and presents mostly in the fifth decade of life. Myeloid sarcoma is a rare initial presentation of acute myeloid leukemia. Previously, it has only been documented in children and younger

patients. We present an unusual case of retro-orbital myeloid sarcoma as an initial presentation of acute myeloid leukemia in a 43 year old male with rearrangement of chromosome 11q23 involving MLL gene. Our case is unique as the cytogenetics involved differs from those previously documented in literature and their impact on the prognosis has not been previously studied. Here we highlight the dilemmas faced in diagnosing this rare variant of acute myeloid leukemia.

Babak Daneshfard has done his PhD from Shiraz University of Medical Sciences (SUMS). He has published more than 10 papers in reputed journals and has been serving as a Reviewer of CAM Journals. He is also an expert in Mind-Body Medicine.

The application of open-ended classifications within the context of philosophy of science would treacherously lead researchers in the field of humanities and logics into abrupt transcendentalism. As a result, there comes on the scene thought of nontranscendental instrumentality by which genealogy of trans-cendence from Kant downwards would not include the procedural judgment by which the void of any void could possibly be defined. In cases where a psychoanalytic void proves to be some position itself qualifying various transcendental desires, then reconstructive methodology is felt to be necessitated to turn us away philosophically from such positions as Sartre or Michel Foucault to one’s more similar to those of Spinoza or Gilles Deleuze.As Lacan asseverates :“Sublimate as much as you like; you have to pay for it with something. And this something is called jouissance. I have to pay for that mystical operation with a pound of flesh.” Transference from the void of asymptoticality and/or tangentiality in not only severe neurotic cases, but also among psychoses appears to be the result of this very quasilogical turn of surrender to negation as personal denoting voids would lead to social-symbolic non-orders. Even the mathesis of negatory negation does not necessarily mean that lines of flight are part and parcel of any freedom from abstract void. This spells that transcendentalism is non-competent in laying its claim to avert the formalism through which logical formalism has to undergo.

Babak Daneshfard has done his PhD from Shiraz University of Medical Sciences (SUMS). He has published more than 10 papers in reputed journals and has been serving as a Reviewer of CAM Journals. He is also an expert in Mind-Body Medicine.

The application of open-ended classifications within the context of philosophy of science would treacherously lead researchers in the field of humanities and logics into abrupt transcendentalism. As a result, there comes on the scene thought of nontranscendental instrumentality by which genealogy of trans-cendence from Kant downwards would not include the procedural judgment by which the void of any void could possibly be defined. In cases where a psychoanalytic void proves to be some position itself qualifying various transcendental desires, then reconstructive methodology is felt to be necessitated to turn us away philosophically from such positions as Sartre or Michel Foucault to one’s more similar to those of Spinoza or Gilles Deleuze.As Lacan asseverates :“Sublimate as much as you like; you have to pay for it with something. And this something is called jouissance. I have to pay for that mystical operation with a pound of flesh.” Transference from the void of asymptoticality and/or tangentiality in not only severe neurotic cases, but also among psychoses appears to be the result of this very quasilogical turn of surrender to negation as personal denoting voids would lead to social-symbolic non-orders. Even the mathesis of negatory negation does not necessarily mean that lines of flight are part and parcel of any freedom from abstract void. This spells that transcendentalism is non-competent in laying its claim to avert the formalism through which logical formalism has to undergo.

 

Nikola Radovic has become a Urology Specialist in 1990. He graduated from School of Medicine, University of Zagreb, where he has also obtained his Master’s degree in 1991 and PhD in 2005. In 1994, he successfully qualified the Statutory Examination in Medical Profession at Medical University of Innsbruck in Austria. Currently, he works at Urology department of University Hospital Centre Zagreb. He had several publications in reputed clinical journals. For his humanitarian work, he was honored twice by Croatian Red Cross.

In urinary bladder, tumors with neuroendocrine differentiation account for less than 1% of primary malignances. Apart from low grade “typical” and intermediate grade “atypical” carcinoids which usually have a bit more favorable outcome for the patient, depending on whether or not there are distant metastases present, small cell neuroendocrine carcinomas (SCNEC) and large cell neuroendocrine carcinomas (LCNEC) are both extremely aggressive and have very poor prognosis. SCNEC is the most common with roughly 500 cases diagnosed annually, while carcinoids and LCNEC are far less common, as there are approximately 20 cases of each type recorded worldwide. Although carcinoids are slowly growing tumors, the final outcome of treatment would primarily depend on disease stage. SCNEC and LCNEC behave similarly, but because of their rarity most effective therapeutic strategies are still largely unknown. In a way LCNEC and SCNEC can be regarded as a systemic disease as micro-metastases may be present in clinically localized disease, so bladder-sparing protocols have a serious drawback because there is a high probability of residual or recurrentcarcinoma occurrence in the preserved bladder. Radical surgery currently seems to be the best option for patients with localized disease, and in combination with other therapeutic modalities it may provide long-term control. However, in approximately 50% of cases, distant metastases are already present at the time of diagnosis and in those patients surgery has limited power to improve the outcome. Also, advanced age along with other multiple co-morbidities typically contribute to poor survival.

Working as Head of Medical Oncology dpt in Clinic for Radiotherapy and Oncology, Clinical Hospital Centre Rijeka and Professor of Internal Medicine on School of Medicine, University of Rijeka, Croatia.Master of science acchieved in 1987, Specialist of Internal medicine 1995, PhD 1999, Assistant Professor 2003, Medical Oncologist subspecialization 2005 and Professor 2009. During education and careear development participated in numerous international courses, including Zagreb, Boston, Miami, New York, Chicago. In the same time participated as international speaker on Postgraduate courses related to oncology, chemotherapy and pain management in Moscow, Hong Kong, Athens, Tokyo, Rovingno and as International Invited speaker in Vienna, Chicago, Moscow, Bucharest, Philadelphia, Athenes, Sarajevo, Bangkok, Fuzhou, Seoul. All together more than 50 participations that covered various aspects of research and management of oncologic patients. Results of work presented in over 50 international publications and 10 books and books chapters. Involved in several projects sponsored by Croatian Ministry of Health. Member of numerous International and National organizations, including IASGO, MASCC, ASCO, ESMO, EACR. Member of Croatian Medical Oncology Society Executive Committee and Vicepresident of Croatian Oncology Foundation.

Anemia is an independent negative prognostic factor for survival in patients with malignant diseases. Pathophysiology of anemia in patients with malignant disease is multifactorial and anemia has effects on tumor hypoxia and is enhancing resistance to antitumor therapy .Erythropoietin (Epo) is a glycoprotein hormone that binds to cells with erythropoietin receptor, thus leading to its activation and stimulation of erythropoiesis.The mature form of Erythropoietin receptor (EpoR) is transferred to the surface of the cells where it becomes available to Epo that binds to it. Epo signaling is initiated by binding of Epo molecule to EpoR that forms a homodimer resulting in activation of two Janus kinase 2 (JAK2), (tyrosine kinase molecules). Epo is pleiotropic hormone with angiogenic and

neurotrophic functions and thus EpoR can act not only on erythroid progenitors but even in endothelial cells, epicardium and pericardium, kidney, pancreas, placenta, and in certain regions of the brain. Tissue hypoxia is the main stimulus of Epo production . Regulation of Epo expression is controlled by several DNA sequences. In a smaller part Epo is excreted through the kidneys and liver. Cancer cells and vascular endothelial cells express EpoR. EpoR is activated by Epo in the systemic circulation, which may be endogenous or synthetic origin. Synthetic forms of Epo are often used in clinical practice in patients with malignant diseases, with the aim of increasing the level of hemoglobin, decreasing the frequency of red blood cell transfusions and improving the quality of life (QoL). There are concerns about possibility that Epo can stimulate the proliferation of tumor cells in vitro but recombinant Epo administered in “in vitro” conditions in different tumor cell lines did not lead to growth stimulation, even in cases where the cell lines expressed EpoR. Additional concerns arise that Epo can act as an angiogenic and, in general, as a cell growth factor. Synthetic forms of Epo can stimulate physiological or pathological angiogenesis and can stimulate EpoR expression in tumor and vascular endothelial cells leading to tumor growth and angiogenesis.In colorectal cancer Epo and EpoR expressions are statistically higher in adenocarcinomas versus mucinous carcinomas and in moderately (G2) versus poorly differentiated (G3)tumors . Overexpression of HIF-1α (Hypoxia Induced Factor) was an independent risk factor for recurrence after curative resection of metastatic CRC. In gastric carcinoma angiogenic potential of Epo is similar to that of VEGF and also, microvessel density in tumor tissue was significantly higher in patients with high Epo or EpoR expression, compared to the patients with low EPO or EpoR expression. The most interesting finding (with no explanation) was that the expression of EpoR was age dependent - it was increased in older age. Hepatocellular carcinoma (HCC) promotes erythrocytosis and is associated with increased levels of Epo. Poorly differentiated HCC has a higher degree of vascularity compared to well-differentiated HCC and tumor progression in HCC is associated with angiogenesis and increase in microvascular density is followed by worse prognosis.Pancreatic Ductal Adenocarcinoma (PDAC) is extremely aggressive tumor and is associated with a high rate of malignancy. Ectopic non-malignant sources of Epo ( hepatocytes and capillaries) are potential sources of additional secretion of Epo and high levels of endogenous Epo is an independent negative prognostic factor for survival in patients with PDAC .Several randomized trials of ESAs in patients who have cancer have recently reported inferior outcomes in tumor progression or survival, raising appropriate concerns about the safety of these agents in oncology. Although the preponderance of the data suggests that EPO/EpoR alter survival large well-controlled trials addressing this issue are still needed.