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Cancer Statistics
Population in 2012: 21.4m
People newly diagnosed with cancer (excluding NMSC) / yr: 78,800
Age-standardised rate, incidence per 100,000 people/yr: 224.2
Risk of getting cancer before age 75:23.1%
People dying from cancer /yr: 48,300
Data from IARC GlobalCan (2012)
Romania Cancer Organisations and Resources
Latest Research Publications Related to Romania

Romania Cancer Organisations and Resources (6 links)

Latest Research Publications Related to Romania

Ács B, Zámbó V, Vízkeleti L, et al.
Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy.
Diagn Pathol. 2017; 12(1):20 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Studies have partly demonstrated the clinical validity of Ki-67 as a predictive marker in the neoadjuvant setting, but the question of the best cut-off points as well as the importance of this marker as a prognostic factor in partial responder/non-responder groups remains uncertain.
METHODS: One hundred twenty patients diagnosed with invasive breast cancer and treated with neoadjuvant chemotherapy (NAC) between 2002 and 2013 were retrospectively recruited to this study. The optimal cut-off value for Ki-67 labeling index (LI) to discriminate response to treatment was assessed by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier curve estimation, log-rank test and cox regression analysis were carried out to reveal the association between Ki-67 categories and survival (DMFS = Distant metastases-free survival, OS = Overall survival).
RESULTS: Twenty three out of 120 patients (19.2%) achieved pathologic complete remission (pCR), whereas partial remission (pPR) and no response (pNR) to neoadjuvant chemotherapy (NAC) was detected in 60.8% and 20.0%, respectively. The distribution of subtypes showed a significant difference in pathological response groups (p < 0.001). Most of the TNBC cases were represented in pCR group. The most relevant cut-off value for the Ki-67 distinguishing pCR from pNR cases was 20% (p = 0.002). No significant threshold for Ki-67 was found regarding DMFS (p = 0.208). Considering OS, the optimal cut-off point occurred at 15% Ki-67 (p = 0.006). The pPR group represented a significant Ki-67 threshold at 30% regarding OS (p = 0.001). Ki-67 and pPR subgroups were not significantly associated (p = 0.653). For prognosis prediction, Ki-67 at 30% cut-off value (p = 0.040) furthermore subtype (p = 0.037) as well as pathological response (p = 0.044) were suitable to separate patients into good and unfavorable prognosis cohorts regarding OS. However, in multivariate analyses, only Ki-67 at 30% threshold (p = 0.029), and subtype (p = 0.008) were independently linked to OS.
CONCLUSIONS: NAC is more efficient in tumors with at least 20% Ki-67 LI. Both Ki-67 LI and subtype showed a significant association with pathological response. Ki-67 LI represented independent prognostic potential to OS in our neoadjuvant patient cohort, while pathological response did not. Additionally, our data also suggest that if a tumor is non-responder to NAC, increased Ki-67 is a poor prognostic marker.

Negovan A, Iancu M, Moldovan V, et al.
The Interaction between GSTT1, GSTM1, and GSTP1 Ile105Val Gene Polymorphisms and Environmental Risk Factors in Premalignant Gastric Lesions Risk.
Biomed Res Int. 2017; 2017:7365080 [PubMed] Free Access to Full Article Related Publications
The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (p = 0.01) as well as in premalignant lesions (p = 0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20-4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19-3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72-4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00-2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37-0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.

Mărginean CO, Meliţ LE, Mărginean MO
Daughter and mother diagnosed with hereditary multiple exostoses: A case report and a review of the literature.
Medicine (Baltimore). 2017; 96(1):e5824 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Hereditary multiple exostoses (HME) or osteochondromatosis is a rare autosomal dominant disease characterized by multiple osteochondromas and skeletal deformities.
PATIENT CONCERNS & DIAGNOSES: We present the case of a 5 years and 9 month-old patient who presented with inferior limb pain for approximately 6 months, associating also deformity of the right index finger for a month. Hand X-ray revealed a radiologic abnormality of the right radius, therefore the child was referred to our clinic for further investigations. The X-rays revealed multiple osteochondromas of the radius, metacarpal bones, hand phalangeal bones, femur, tibia, fibula, metatarsal bones, and foot phalangeal bones. We mention that the same radiological aspect was identified in the case of the patient's mother, undiagnosed until that moment.
OUTCOMES: The particularity of this case consists in identification of a rare genetic pathology, HME in a 5-year-old patient, without any known familial history, after the occurrence of a nontraumatic joint dislocation of the right index finger.
CONCLUSION: HME is a rare genetic condition, without a curative treatment, burdened by multiple complications, and whose diagnosis is usually established during childhood.

Pavel IZ, Danciu C, Oprean C, et al.
In Vitro Evaluation of the Antimicrobial Ability and Cytotoxicity on Two Melanoma Cell Lines of a Benzylamide Derivative of Maslinic Acid.
Anal Cell Pathol (Amst). 2016; 2016:2787623 [PubMed] Free Access to Full Article Related Publications
Maslinic acid is a pentacyclic triterpene extracted from olives that has been systematically reported to exert several therapeutic effects, such as antitumoral, antidiabetic, antioxidant, anti-inflammatory, antiparasitic, and antiviral properties. Recently, new derivatives of maslinic acid have been obtained and expanded the spectrum of biological activities and improved the existing ones. The present study was meant to perform the in vitro assessment of the (i) cytotoxic effects of a benzylamide derivative of maslinic acid ("EM2") (benzyl (2α, 3β) 2,3-diacetoxy-olean-12-en-28-amide) on B164A5 murine melanoma and A375 human malignant melanoma cell lines and the (ii) antimicrobial activity of the compound on several bacterial strains, respectively. We obtained a dose-dependent cytotoxic effect of EM2 that was particularly relevant to the murine cell line. As on the antibacterial activity, EM2 was tested on 10 bacterial strains Bacillus cereus, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, Escherichia coli, Yersinia enterocolitica, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa and one fungus Candida albicans. A significant antimicrobial effect was recorded for Streptococcus pyogenes and Staphylococcus aureus.

Chinezu L, Vasiljevic A, Trouillas J, et al.
Silent somatotroph tumour revisited from a study of 80 patients with and without acromegaly and a review of the literature.
Eur J Endocrinol. 2017; 176(2):195-201 [PubMed] Related Publications
BACKGROUND: Silent somatotroph tumours are growth hormone (GH) immunoreactive (IR) pituitary tumours without clinical and biological signs of acromegaly. Their better characterisation is required to improve the diagnosis.
MATERIALS AND METHODS: Twenty-one silent somatotroph tumours were compared to 59 somatotroph tumours with acromegaly. Tumours in each group were classified into GH and plurihormonal (GH/prolactin (PRL)/±thyroid-stimulating hormone (TSH)) and into densely granulated (DG) and sparsely granulated (SG) types. The two groups were then compared with regards to proliferation (Ki-67, p53 indexes and mitotic count), differentiation (expression of somatostatin receptors SSTR2A-SSTR5 and transcription factor Pit-1) and secretory activity (% of GH- and PRL-IR cells).
RESULTS: The silent somatotroph tumours represented 2% of all tested pituitary tumours combined. They were more frequent in women than in men (P = 0.002), more frequently plurihormonal and SG (P < 0.01), with a lower percentage of GH-IR cells (P < 0.0001) compared to those with acromegaly. They all expressed SSTR2A, SSTR5 and Pit-1. The plurihormonal (GH/PRL/±TSH) tumours were mostly observed in women (sex ratio: 3/1) and in patients who were generally younger than those with acromegaly (P < 0.001). They were larger (P < 0.001) with a higher Ki-67 index (P = 0.007).
CONCLUSIONS: The silent somatotroph tumours are not uncommon. Their pathological diagnosis requires the immunodetection of GH and Pit-1. They are more frequently plurihormonal and more proliferative than those with acromegaly. A low secretory activity of these tumours might explain the normal plasma values for GH and insulin-like growth factor 1 (IGF1) and the absence of clinical signs of acromegaly.

Munteanu C, Pirici D, Stepan AE, et al.
Maxillary calcifying epithelial odontogenic tumor with sinus and buccal vestibule extension: a case report and immunohistochemical study.
Diagn Pathol. 2016; 11(1):134 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Calcifying epithelial odontogenic tumor (CEOT) is a rare benign neoplasia, locally aggressive, that tends to invade bone and adjacent soft tissues. This case report describes the thirteenth known case of CEOT with maxillary sinus extension and the second one that also involves the buccal vestibule mucosa with peculiar histopathological and immunohistochemical data.
CASE PRESENTATION: Here we report the case of a 45-year-old female with a CEOT diagnosed and treated at the Oral & Maxillofacial Surgery Department, County Clinical Emergency Hospital of Craiova, Romania. The clinical and imaging investigation revealed an intraosseous tumor developed from the left posterior maxilla with maxillary sinus and buccal vestibule mucosa extension. Histopathology found an epithelium-rich CEOT variant, but with scattered S100 positive clear cells, focal small rounded cementum-like deposits and areas with some degree of nuclear pleomorphism. The immunohistochemical investigations emphasised its local aggressiveness behavior with involvement of multiple molecular mechanisms that underlie tumor invasiveness. A subtotal maxillectomy was performed followed by defect reconstruction.
CONCLUSIONS: We discuss the relevant clinicopathological features of an aggressive rare case of CEOT with maxillary sinus extension and buccal vestibule mucosa involvement. The immunohistochemical study suggests its utility in attempting to assess the degree of local tumor aggressiveness and thus in adopting the most efficient therapeutic attitude.

Gaje PN, Amalia Ceausu R, Jitariu A, et al.
Mast Cells: Key Players in the Shadow in Oral Inflammation and in Squamous Cell Carcinoma of the Oral Cavity.
Biomed Res Int. 2016; 2016:9235080 [PubMed] Free Access to Full Article Related Publications
Although mast cells (MCs) have been discovered over 130 years ago, their function was almost exclusively linked to allergic affections. At the time being, it is well known that MCs possess a great variety of roles, in both physiologic and pathologic conditions. In the oral tissues, MCs release different proinflammatory cytokines, tumor necrosis factor alpha (TNF-α), that promote leukocyte infiltration in various inflammatory states of the oral cavity. These cells play a key role in the inflammatory process and, as a consequence, their number changes in different pathologic conditions of the oral cavity, like gingivitis, periodontitis, and so on. MCs also represent a rich source of proteases, especially of mast cell tryptase and chymase, which directly degrade the extracellular matrix through their proteolytic activity and thus indirectly stimulate angiogenesis and facilitate invasion and metastasis. It may be stated that mast cells could have an impact on primary tumor development, progression, and metastases in oral squamous cell carcinoma. By understanding the role of mast cells in the pathogenesis of different inflammatory and tumor diseases of the oral cavity, these cells may become therapeutic targets that could possibly improve the prognosis and survival of these patients.

Schabel C, Horger M, Kum S, et al.
Simplified response monitoring criteria for multiple myeloma in patients undergoing therapy with novel agents using computed tomography.
Eur J Radiol. 2016; 85(12):2195-2199 [PubMed] Related Publications
INTRODUCTION: Multiple myeloma is a malignant hematological disorder of the mature B-cell lymphocytes originating in the bone marrow. While therapy monitoring is still mainly based on laboratory biomarkers, the additional use of imaging has been advocated due to inaccuracies of serological biomarkers or in a-secretory myelomas. Non-enhanced CT and MRI have similar sensitivities for lesions in yellow marrow-rich bone marrow cavities with a favourable risk and cost-effectiveness profile of CT. Nevertheless, these methods are still limited by frequently high numbers of medullary lesions and its time consumption for proper evaluation.
OBJECTIVE: To establish simplified response criteria by correlating size and CT attenuation changes of medullary multiple myeloma lesions in the appendicular skeleton with the course of lytic bone lesions in the entire skeleton. Furthermore to evaluate these criteria with respect to established hematological myeloma-specific parameters for the prediction of treatment response to bortezomib or lenalidomide.
MATERIALS AND METHODS: Non-enhanced reduced-dose whole-body CT examinations of 78 consecutive patients (43 male, 35 female, mean age 63.69±9.2years) with stage III multiple myeloma were retrospectively re-evaluated. On per patient basis, size and mean CT attenuation of 2-4 representative lesions in the limbs were measured at baseline and at a follow-up after a mean of 8 months. Results were compared with the course of lytical bone lesions as well with that of specific hematological biomarkers. Myeloma response was assessed according to the International Myeloma Working Group (IMWG) uniform response criteria. Testing for correlation between response of medullary lesions (Respmed) and response of all myeloma manifestations including osteolyses (Resptotal) was performed using the corrected contingency coefficient (Ccorr).
RESULTS: The correlation between Respmed based on length diameter and transverse diameter and Resptotal was perfect (Ccorr=1.0; p<0.0001) whereas the correlation based on density was moderate (Ccorr=0.54; p<0.0001). The evaluation of simplified response criteria with a measurement of only 2 medullary lesions yielded the best sensitivity and specificity valued for treatment-induced changes for the length diameter evaluation with 94.4%/95.7% for prediction of progressive disease and 78.6%/93.3% for prediction of therapy response. There were no significant differences between patients treated with bortezomib and lenalidomide (p>0.05).
CONCLUSION: Measurements of size of a minimum of two medullary lesions is sufficient for response assessment and correlates very well with the course of lytic bone lesions and that of hematologic parameters.

Ciortea R, Berceanu C, Măluţan AM, et al.
Intraperitoneal Fat through GRP78: A Risk Factor for Endometrial Cancer.
Anal Cell Pathol (Amst). 2016; 2016:3496538 [PubMed] Free Access to Full Article Related Publications
Introduction. The identification of biological markers that indicate an increased risk for the development or recurrence of endometrial cancer (EC) in obese women might be useful for decreasing EC mortality and morbidity. Glucose-regulated protein 78 (GRP78) is a major protein of the endoplasmic reticulum expressed in all normal cells. Overexpression of GRP78 has been reported to be a tumoral biomarker. Increased detection of GRP78 is positively correlated with the tumoral stage and prognosis. This study aimed to identify a correlation between intraperitoneal fat, plasma GRP78 levels, and EC. Materials and Methods. Two groups of patients were included in the study: group I, 44 patients diagnosed with EC, and group II, 44 patients without gynecological pathology or inflammatory disorders. Visceral fat was determined by ultrasound and plasma GRP78 levels were measured. Results. Plasma GRP78 levels were significantly higher in patients with EC compared to the control group. Intraperitoneal fat was in a positive linear correlation with the plasma GRP78 level (p < 0.0001). Conclusion. The measurement of the GRP78 level associated with the determination of intraperitoneal fat can be a useful predictor for EC.

Ion A, Popa IM, Papagheorghe LM, et al.
Proteomic Approaches to Biomarker Discovery in Cutaneous T-Cell Lymphoma.
Dis Markers. 2016; 2016:9602472 [PubMed] Free Access to Full Article Related Publications
Cutaneous T-cell lymphoma (CTCL) is the most frequently encountered type of skin lymphoma in humans. CTCL encompasses multiple variants, but the most common types are mycosis fungoides (MF) and Sezary syndrome (SS). While most cases of MF run a mild course over a period of many years, other subtypes of CTCL are very aggressive. The rapidly expanding fields of proteomics and genomics have not only helped increase knowledge concerning the carcinogenesis and tumor biology of CTCL but also led to the discovery of novel markers for targeted therapy. Although multiple biomarkers linked to CTCL have been known for a relatively long time (e.g., CD25, CD45, CD45RA, and CD45R0), compared to other cancers (lymphoma, melanoma, colon carcinoma, head and neck cancer, renal cancer, and cutaneous B-cell lymphoma), information about the antigenicity of CTCL remains relatively limited and no dependable protein marker for CTCL has been discovered. Considering the aggressive nature of some types of CTCL, it is necessary to identify circulating molecules that can help in the early diagnosis, differentiation from inflammatory skin diseases (psoriasis, nummular eczema), and aid in predicting the prognosis and evolution of this pathology. This review aims to bring together some of the information concerning protein markers linked to CTCL, in an effort to further the understanding of the convolute processes involved in this complex pathology.

Marincaş AM, Prunoiu VM, Cirimbei C, et al.
Digestive Decompression to Prevent Digestive Fistulas After Gastric Neoplasm Resection.
Chirurgia (Bucur). 2016 Sept-Oct; 111(5):400-406 [PubMed] Related Publications
Introduction: The risk of digestive fistula in patients operated for gastric neoplasm is increased due to biological imbalances generated by the cancer's progression, by diagnosis in advanced stages, and by the scale of intervention. Under these circumstances the use of some technical means to protect digestive sutures in these patients is useful.
AIM: To analyse the efficiency of technical means to protect the digestive sutures in patients operated in various stages of development of gastric cancer. Material and Methods: We conducted a retrospective study on a group of 130 patients operated for gastric cancer in the 1st General Surgery and Oncology Clinic of the Bucharest Institute of Oncology, between 2010-2014. Results: 38.46% of the patients in the study group presented stage IV cancer with multiple complications and biological imbalances. 52 total gastrectomies and 40 gastric resections were carried out, while in 34 patients palliative "tumour excisions" or other types of palliative surgery were performed. In 15 of the cases with gastric resection a duodenal decompression probe was used, while in 13 of the patients with total gastrectomy an oeso-jejunal aspiration probe together with an oeso-jejunal feeding probe were used as additional technical measures to prevent fistula formation. The incidence of duodenal stump fistula was 7.69%, that of oeso-jejunal anastomosis fistula was 2.3%, with an overall mortality of 3.07% and that of gastro-jejunal anastomosis fistula was 0.76%.
CONCLUSION: Given the risk of fistula development in patients with gastric cancer, as well as the increased risk in advanced stages of cancer development, we consider that the use of technical means of protection of digestive sutures is beneficial and opportune, lowering the incidence of fistulas, reducing their output, pathophysiological effects, and mortality.

Gődény M, Lengyel Z, Polony G, et al.
Impact of 3T multiparametric MRI and FDG-PET-CT in the evaluation of occult primary cancer with cervical node metastasis.
Cancer Imaging. 2016; 16(1):38 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: This study aimed to determine the ability of multimodal evaluation with multiparametric 3T-MRI (MPMRI) and positron emission tomography - computed tomography (PET/CT) to detect cancer of unknown primary origin (CUP) with neck lymph node (LN) metastasis.
METHODS: The study group comprised 38 retrospectively analysed consecutive patients with LN metastasis in the head and neck (HN) region without known primary tumours (PTs). Statistical values of 3T-MRI and of FDG-PET/CT scans were evaluated.
RESULTS: Of the 38 CUPs, conventional native T1-, T2-weighted and STIR sequences detected 6 PTs. Native sequences plus diffusion-weighted imaging (DWI) found 14-, and with fat suppression contrast-enhanced T1-weighted measurement as well as with the complex MPMRI found 15 primaries and with PET/CT 17 CUPs could be evaluated, respectively. The detection rates were 15.8, 36.8, 39.5, 39.5 and 44.7 % for conventional native MRI, native plus DWI, native with contrast-enhanced MRI (CE-MRI), for MPMRI, and for PET/CT, respectively. The overall detection rate proved by histology was 47.4 %. PET/CT provided the highest sensitivity (Sv: 94.4 %) but a lower specificity (Sp: 65.0 %), using MPMRI (Sv: 88.2 %) the specificity increased to 71.4 %. DWIincreased specificity of the native sequences (Sp: 76.2 %). Conventional native sequences plus DWI as well as 3T-MPMRI and PET/CT were same accurate (Acc: 79.0 %) and had similar likelihood ratio (LR: 3.42, 3.03 and 2.62) in detecting unknown PT sites.
CONCLUSIONS: The accuracy of FDG-PET/CT and MPMRI in case of CUP in finding the primary cancer in the neck regions is identical. While using PET/CT whole body information can be obtained in one examination. MPMRI shows the local soft tissue status more accurately. In cases of CUP PET/CT should be the first method of choice if it is available. MPMRI can clarify the exact primary tumor stage, and it can be advantageous in clarifying the prognostic factors, which is necessary in case of advanced tumor stage and when surgery is under consideration. In case low N stage is likely after the clinical examination and wait and see policy can be considered, MPMRI is recommended, and in this case the significance the of radiation free MPMRI is increasing.

Rotar IC, Dumitras DE, Popp RA, et al.
VEGF +936 C/T Genetic Polymorphism in Patients with Cervical Dysplasia.
Anal Cell Pathol (Amst). 2016; 2016:6074275 [PubMed] Free Access to Full Article Related Publications
Aim. The present study aims to analyze the potential role of VEGF +936 C/T polymorphism in cervical intraepithelial neoplasia. Material and Method. One hundred and eighty-six patients were included in the study: 75 cases (patients diagnosed with CIN) and 111 controls (negative for both HPV testing and cytology). For each patient a single visit was scheduled when colposcopy was performed. From cervical specimen, cytology and HPV testing were performed and from peripheral blood VEGF +936 genotyping was determined. For statistical analysis purposes OR and chi-square were used at a level of significance of <0.05. Results. No link has been found in the detection of CT genotype in cases versus controls, OR = 0.8295, [0.42, 1.62]. An inverse correlation has been found between T allele and HSIL, OR = 0.2121, [0.0473, 0.9517], p = 0.0866. Conclusion. No link has been found between VEGF +936 C/T and cervical intraepithelial neoplasia.

Cimpean AM, Cobec IM, Ceaușu RA, et al.
Platelet Derived Growth Factor BB: A "Must-have" Therapeutic Target "Redivivus" in Ovarian Cancer.
Cancer Genomics Proteomics. 2016 11-12; 13(6):511-517 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: We aimed to validate PDGF-BB protein expression by RNAscope, a sensitive method for PDGF-BB mRNA evaluation on paraffin embedded (FFPE) specimens of ovarian tumors.
MATERIALS AND METHODS: Seventy-five FFPE ovarian cancer biopsies were assessed by immunohistochemistry followed by PDGF-BB mRNA RNAscope validation.
RESULTS AND CONCLUSION: Dual PDGF-BB expression in tumor and stromal cells have been observed, being highly suggestive for PDGF-BB mediated stromal-tumor cells reciprocal interaction in ovarian cancer (p=0.008). It seems that the nuclear expression of the PDGF-BB represents a negative prognostic factor in ovarian tumors. Being a controversial issue in the literature, PDGF-BB nuclear expression detected by immunohistochemistry was validated by RNAscope in situ hybridization. More than 65% of cases had PDGF-BB mRNA amplification, confirming immunohistochemical results. We herein validated PDGF-BB as a potential therapeutic and prognostic tool of ovarian cancer aggressiveness.

Cobec IM, Sas I, Pirtea L, et al.
Podoplanin as Key Player of Tumor Progression and Lymph Vessel Proliferation in Ovarian Cancer.
Anticancer Res. 2016; 36(10):5265-5272 [PubMed] Related Publications
BACKGROUND/AIM: Podoplanin plays a key role in tumor progression and metastasis. We evaluated lymphatics proliferation rate and podoplanin expression in tumor cells of ovarian carcinoma.
MATERIALS AND METHODS: Seventy-five paraffin-embedded specimens of ovarian cancer were immunohistochemically assessed in order to quantify peritumoral (LMVDP) and intratumoral (LMVDT) lymphatic microvessel density of proliferating lymphatics and for podoplanin variability in tumor cells.
RESULTS AND CONCLUSION: LMVDT correlated with proliferating tumor vessels located in the peritumoral area (p=0.024) and with the number of mature vessels located in the intratumoral area (p<0.0001), while LMVDP correlated with peritumoral mature vessels (p<0.000l). Proliferating tumor cells at the invasive front were highly positive for podoplanin. To the best of our knowledge, this study represents the first assessment of lymphatic endothelial cell proliferation correlated with podoplanin expression in tumor cells from ovarian cancer. Our data support podoplanin as a potential target that may help reduce ovarian cancer dissemination and lymphatic metastasis.

Cioca A, Olteanu EG, Gisca MD, et al.
Expression of EGFR in Paired New and Recurrent Glioblastomas.
Asian Pac J Cancer Prev. 2016; 17(9):4205-4208 [PubMed] Related Publications
BACKGROUND: The aim of this study was to analyse the expression of EGFR in newly diagnosed and recurrent glioblastoma multiforme (GBM).
MATERIALS AND METHODS: Our study included a total of 48 paired samples collected from 24 patients diagnosed with GBM. The intensity of EGFR cytoplasmatic staining was scored on a scale of 1-3+ (weak, intermediate or strong).
RESULTS: We found EGFR overexpression in 23 patients (96%) with newly diagnosed GBM, while all recurrent tumours overexpressed EGFR. Ten recurrent tumours (42%) had a lower expression than their new counterpart 13 tumours (54%) had a similar expression, and only one case (2%) had increased expression on recurrence. The expression of EGFR in newly diagnosed GBM was significantly correlated with EGFR expression in recurrent tumour (p = 0.036). In addition, new GBMs with strong EGFR expression had a mean relapse-free interval of 11.5 months (p=0.017). A benefit of combined therapy was observed in the radiotherapy-plus-chemotherapy group where the average time was 11 months (p=0.011), as compared with surgery/radiotherapy alone (average time 6.8 months).
CONCLUSIONS: The present data show that EGFR is overexpressed in paired GBMs. The discrepancies of EGFR expression between the primary tumour and the recurrence suggest heterogeneity of GBMs but also unity at relapse.

Sarbu I, Socolov D, Socolov R, et al.
Hydrocephalus secondary to chemotherapy in a case of prenatally diagnosed giant immature grade 3 sacrococcygeal teratoma: A case report and literature review.
Medicine (Baltimore). 2016; 95(43):e5244 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Sacrococcygeal teratoma (SCT) is a rare tumor in the general population, arising from multipotent stem cells. Whereas most of the cases diagnosed postnatally have good prognosis, the rate of mortality and morbidities associated with prenatally diagnosed SCT remain high, with a reported mortality rate of 30% to 50%. The outcome of fetal SCT can be unpredictable, with some cases with slow growth during fetal life, whereas others grow rapidly, causing multiple complications; also, some of these tumor will develop triggering fetal (preterm delivery, high-output cardiac failure, hydrops fetalis, intrauterine death) or maternal complications (distocia, placentomegaly, maternal mirror syndrome-preeclampsia). Even if prenatal criteria seem to define tumors at risk, it can not totally predict postnatal outcome as treatment-related complications can occur.We present a case of giant prenatally detected SCT. The case was diagnosed at 24th week of gestation, and was closely monitored by serial ultrasound. The morphology of the lesion was defined by fetal MRI performed at 25th week of gestation. A baby girl with a huge sacrococcygeal tumor was born and surgery was performed 48 hours later. Pathological examination revealed a grade 3 immature teratoma. Because of the tumor size and pathological aspect, adjuvant chemotherapy was considered. The outcome was complicated by wound infection, sepsis, and subsequent hydrocephalus, induced by chemotherapy-induced immunosuppression.
CONCLUSION: Our case emphasizes not only the importance of prenatal monitoring of these cases but also the importance of individualized postnatal management, as unusual and unpredictable complications can occur and affect outcome.

Mărginean CO, Mărginean MO, Simu I, et al.
Giant tubular adenoma with malignancy clinical characteristics in a female teenager: Case report and a review of the literature.
Medicine (Baltimore). 2016; 95(40):e4805 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Adenomas of the colon are usually benign tumors which carry a tendency for malignancy. These tumors can be villous, tubular, tubulovillous, or sessile serrated. Those with adenomatous structure can develop malignant characteristics in 1.5% to 9.4% of cases.
METHODS: We present a case report of a 16-year-old female adolescent with an adenoma of the descending colon. History revealed prolonged diarrheic syndrome for the past 6 months, repeated headache, and a weight loss of ∼5 kg in the past month. One week before the admission, the patient presented an episode of inferior digestive hemorrhage.
RESULTS: On admission laboratory tests revealed iron deficiency anemia, and a mildly increased erythrocyte sedimentation rate. The abdominal ultrasound revealed an inhomogeneous mass of the descending colon and 2 hyperechoic lesions in the liver. The colonoscopy showed a tumor of the descending colon, a tubular adenoma according to the pathological examination. Additionally, we noted an atypical presentation of the tumor and the signs of mild dysplasia identified at the pathological examination.
CONCLUSION: Weight loss, bowel transit alterations, loss of appetite, and inferior hemorrhage in an adolescent can be symptoms of a benign or malignant tumor of the colon.

Bianchi R, Cozzi G, Petralia G, et al.
Multiparametric magnetic resonance imaging and frozen-section analysis efficiently predict upgrading, upstaging, and extraprostatic extension in patients undergoing nerve-sparing robotic-assisted radical prostatectomy.
Medicine (Baltimore). 2016; 95(40):e4519 [PubMed] Free Access to Full Article Related Publications
To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) in predicting upgrading, upstaging, and extraprostatic extension in patients with low-risk prostate cancer (PCa). MpMRI may reduce positive surgical margins (PSM) and improve nerve-sparing during robotic-assisted radical prostatectomy (RARP) for localized prostate cancer PCa.This was a retrospective, monocentric, observational study. We retrieved the records of patients undergoing RARP from January 2012 to December 2013 at our Institution. Inclusion criteria were: PSA <10 ng/mL; clinical stage

Pirtea L, Grigoraş D, Matusz P, et al.
Age and HPV type as risk factors for HPV persistence after loop excision in patients with high grade cervical lesions: an observational study.
BMC Surg. 2016; 16(1):70 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Persistent infections with high risk human papillomaviruses (HR-HPV) cause virtually all cervical cancers.
METHODS: An observational study was conducted aiming to estimate the rate of HPV infection persistence after LEEP in patients with high grade squamous intraepithelial lesions (HSIL). Moreover, the study investigated if persistence is age related. For this reason a total of 110 patients were included between January 2010 and June 2015.
RESULTS: At 6 months after LEEP the overall HPV infection persistence rate was 40.9 %, at 12 months 20 % and at 18 months 11.8 %. Type 16 showed the highest persistence rate: 27.3 % at 6 months, 12.7 % at 12 months and 10 % at 18 months after LEEP. The persistence for HPV type 16 at 6 months after LEEP was significantly higher in the group > =36.5 years old compared to the persistence rate in the group <36.5 years old (p = 0.0027, RR = 2.75, 95 %ϵ(1.34; 5.64)) (see Table 3).
CONCLUSIONS: LEEP does not completely eradicate HPV infection. HPV persistence rate after LEEP is higher in infections with type 16 and in women older than 36.5 years.

Ungureanu BS, Teodorescu CM, Săftoiu A
Magnetic Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy.
J Gastrointestin Liver Dis. 2016; 25(3):375-83 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver, ranking as the second most common cause of death from cancer worldwide. Magnetic nanoparticles (MNPs) have been used so far in tumor diagnosis and treatment, demonstrating great potential and promising results. In principle, three different approaches can be used in the treatment of tumors with superparamagnetic iron oxide nanoparticles: magnetically induced hyperthermia, drug targeting and selective suppression of tumor growth. This review focuses on the use of iron oxide nanoparticles for the diagnosis and treatment of liver cancer and offers a walkthrough from the MNPs imaging applicability to further therapeutic options, including their potential flaws. The MNP unique physical and biochemical properties will be mentioned in close relationship to their subsequent effects on the human body, and, also, their toxic potential will be noted. A presentation of what barriers the MNPs should overcome to be more successful will conclude this review.

Graur F, Furcea L, Mois E, et al.
Analysis of p53 Protein Expression in Hepatocellular Carcinoma.
J Gastrointestin Liver Dis. 2016; 25(3):345-9 [PubMed] Related Publications
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) has a growing incidence and studies regarding the risk factors or pathogenesis for this type of carcinoma benefit special interest. This study evaluates the correlations between p53 protein expression and clinical and laboratory factors in patients with HCC.
METHODS: The study group included 76 patients diagnosed with HCC, either by biopsy or after surgical resection (with curative intent). Immunohistochemistry for p53 protein assessment was performed in all patients. Correlations between the protein 53 expression and age, tumour size, viral infection, liver cirrhosis were performed using the chi-square test (Pearson's chi-square) together with the contingency coefficient Kendall's coefficient in the tau-b form.
RESULTS: In the study group, 51 patients were male (67%) and 25 female (33%). Cirrhosis due to hepatitis virus B or C infection (in a proportion of 63% of the study group) was not significantly associated with the presence of HCC. Altered expression of p53 protein was observed in 69 patients (91%). The relationship between p53 protein expression and patient sex (p=0.067), age (p=0.531), tumour size (p=0.270), presence of hepatitis B and C viral infections (p=0.7), and of liver cirrhosis (p=0.511) was not statistically significant.
CONCLUSION: The p53 protein expression was not significantly associated with the demographic characteristics of the patients, tumour size, presence of viral B and C infections or liver cirrhosis.

Vlad C, Kubelac P, Onisim A, et al.
Expression of CDCP1 and ADAM12 in the ovarian cancer microenvironment.
J BUON. 2016 Jul-Aug; 21(4):973-978 [PubMed] Related Publications
PURPOSE: The tumor microenvironment in ovarian cancer (OC) seems to play an important role, and besides tumor cells, biomarkers can derive from endothelial cells. We investigated CDCP1 and ADAM12 expression in relation with other clinical and pathological characteristics in OC patients.
METHODS: We retrospectively evaluated patient files between 2006-2011. A histochemical score was developed to evaluate tumor staining, the microvessel density (MVD), and stromal expression patterns for both ADAM12 and CDCP1. A CD34 antibody was used to assess tumor MVD.
RESULTS: 102 patients were selected and 83% had FIGO stage III/IV. A high CDCP1 tumor score correlated significantly with a shorter overall survival (OS) (p<0.01). Cases with positive CDCP1 had an elevated CD34 MVD (p<0.01). An absent/low ADAM12 tumor score correlated with significantly improved OS (p<0.01). Mean CD34 MVD was higher in cases with positive ADAM12 MVD (p=0.012).
CONCLUSIONS: Our results indicate that both tumor markers are negative prognostic factors for overall survival and additional studies are required to validate their future potential.

Zhong FL, Mamaï O, Sborgi L, et al.
Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.
Cell. 2016; 167(1):187-202.e17 [PubMed] Related Publications
Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.

Tănase A, Tomuleasa C, Mărculescu A, et al.
First Successful Haploidentical Stem Cell Transplantation in Romania.
Rom J Intern Med. 2016; 54(3):194-200 [PubMed] Related Publications
Hematopoietic stem cell transplantation is an established treatment for many malignant and non-malignant haematological disorders. In the current case report, we describe the first haploidentical stem cell transplantation, used for the first time in Romania, the case of a 33 year-old young woman diagnosed with Hodgkin's lymphoma that has underwent a haploSCT after she relapsed from several chemotherapy regimens, as well as after an autologous stem cell transplantation. This success represents a prèmiere in Romanian clinical hematology, being the first case of a haploSCT in Romania, as well as in South-Eastern Europe.

Turcu G, Nedelcu RI, Ion DA, et al.
CEACAM1: Expression and Role in Melanocyte Transformation.
Dis Markers. 2016; 2016:9406319 [PubMed] Free Access to Full Article Related Publications
Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination.

Voiculescu V, Calenic B, Ghita M, et al.
From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers.
Dis Markers. 2016; 2016:4517492 [PubMed] Free Access to Full Article Related Publications
Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies.

Raica M, Jitariu AA, Cimpean AM
Lymphangiogenesis and Anti-lymphangiogenesis in Cutaneous Melanoma.
Anticancer Res. 2016; 36(9):4427-35 [PubMed] Related Publications
Cutaneous malignant melanoma is an aggressive tumor characterized by early lymph node metastasis and bad prognosis. Although the spread of tumor cells in the regional lymph nodes is very important in the staging, prognosis and therapeutic strategy of malignant melanoma, the mechanism(s) of initial lymphatic vessels invasion is are) not completely understood. In the present review, we analyze the main factors involved in melanoma-associated lymphangiogenesis, based on existing available evidence. Currently, there are no anti-lymphangiogenic drugs approved for clinical trials. On the other hand, inhibition of lymph node metastasis has been demonstrated in experimental models by inhibiting tumor-associated lymphangiogenesis.

Ferro M, Terracciano D, Buonerba C, et al.
The emerging role of obesity, diet and lipid metabolism in prostate cancer.
Future Oncol. 2017; 13(3):285-293 [PubMed] Related Publications
Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.

Lupu M, Caruntu C, Ghita MA, et al.
Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma.
Dis Markers. 2016; 2016:9831237 [PubMed] Free Access to Full Article Related Publications
Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC.

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