Histological Origin Research Articles

Neoadjuvant treatment by ECT in cutaneous malignant neoplastic lesions

Electrochemotherapy (ECT) is a local treatment and its use has been standardised for cutaneous nodules of any histological origin. In this study, we use ECT as a neoadjuvant therapy to reduce the size of neoplastic lesions to obtain an ideal cleavage plane where vital or very important vascular and/or nervous structures are separated from the tumour, thus allowing a radical surgical excision, which is otherwise unfeasible. In their retrospective study, the authors identified 41 patients who were treated at our institution with neoadjuvant intent. ECT was performed under general (30 patients, 73%), regional (9 patients, 22%) or local anaesthesia with sedation (2 patients, 5%). At a median time of 2 months (range, 0.3-9) after neoadjuvant ECT, all patients underwent surgical intervention to resect the residual tumour. Median reduction of tumour volume after ECT was 55% (range, 10%-65%). After ECT plus surgery, 25 patients (61%) had complete response (CR), 16 patients (39%) partial response (PR). The percentage of CR in patients with larger lesions (>100 mm) was 27%, in patients with smaller lesions (≤100 mm) was 73% (p = 0.0119). Major side effects after ECT were: bleeding and/or ulceration (54%) and pain (59%) naturally resolved within 1-2 months. Side effects observed after surgery were: necrosis of the flap (N = 3), a case of diastasis of the donor site. Median survival time in CR patients was 53 months (range, 4-108), whereas in PR survival was 23 months (range, 5-126), p = 0.0400. ECT represents a safe and effective therapeutic approach that could be effectively used for neoadjuvant purposes.

EXTH-66. THERAPEUTIC VULNERABILITIES AND RADIOSENSITIZATION INDUCED BY IDH MUTANT DEPENDENT SUPPRESSION OF DNA DAMAGE REPAIR IN GLIOMA AND CHOLANGIOCARCINOMA

Abstract Mutations in isocitrate dehydrogenase (IDH) identified across cancer types lead to global changes to the epigenome that drive tumorigenesis. Yet, effectiveness of targeted therapies against mutant IDH remains unclear. Here we demonstrate that IDH-mutant glioma and cholangiocarcinoma patient specimens display elevated overall DNA damage responses. With tissue culture and multiple preclinical animal models of glioma and cholangiocarcinoma, we report that the reduced efficiency of DNA damage repair conferred by mutant IDH can be exploited by PARP inhibitors. Moreover, pharmacological effects of PARP inhibitors are dramatically enhanced by introducing concurrent, local ionizing radiation treatment to the animals. Thus, our study characterized the synergy of PARPi and radiation specifically towards IDH-mutant tumors, pointing out that in addition to ongoing trials using PARPi as mono agent, clinical trials that combine PARPi and radiation should be specifically considered. Furthermore, PARPi + RT may represent a readily translatable approach that is selective for tumor cells, transcends histologic origin, and has potential to improve outcomes in multiple diseases.

Trends in peritoneal surface malignancies: evidence from a Czech nationwide population-based study

BackgroundThe aim of this study is to identify the incidence trends of primary and secondary peritoneal surface malignancies in a representative Czech population.MethodsData were obtained from patients registered in the Czech National Cancer Registry between 1979 and 2016. The incidence rates were analyzed between 2012 and 2016. To observe the incidence trends, we analyzed the data from two time periods, 1979–2005 and 2006–2016. The analyzed data included age, sex, and the histological types and primary origins of the malignancies. The Cochrane-Armitage test for linear trends was used for verification of the null hypothesis. The significance level established for hypothesis testing was p = 0.05.ResultsBetween 2012 and 2016, 230 patients with primary peritoneal tumors were identified and divided into the following groups according to their “International Statistical Classification of Diseases and Related Health Problems, 10th revision” codes: malignant neoplasm of specified parts of the peritoneum (C48.1); malignant neoplasm of the peritoneum, unspecified (C48.2); and malignant neoplasm of overlapping sites of the retroperitoneum and peritoneum (C48.8). Moreover, 549 primary tumors of the appendix (C18.1, encompassing all appendiceal malignancies) and 3137 secondary synchronous peritoneal carcinomatoses of other primary origins were documented. The age-adjusted incidence of primary peritoneal tumors in 2012–2016 was 4.36/year/1,000,000 inhabitants. The age-adjusted incidence of synchronous secondary peritoneal malignancies in 2014–2016 was 99.0/year/1,000,000 inhabitants. The diagnoses of primary peritoneal malignancies followed a stable trend between 1979 and 2016. However, the incidences of primary tumors of the appendix increased by 76.7%.ConclusionsThe data produced in our study ought to clarify the status of peritoneal surface malignancies in the Czech Republic, which can lead to improved planning and development of therapeutic interventions as well as physician training.

Immunotherapy Based on Dendritic Cell-Targeted/-Derived Extracellular Vesicles-A Novel Strategy for Enhancement of the Anti-tumor Immune Response.

Dendritic cell (DC)-based anti-tumor vaccines have great potential for the treatment of cancer. To date, a large number of clinical trials involving DC-based vaccines have been conducted with a view to treating tumors of different histological origins. However, DC-based vaccines had several drawbacks, including problems with targeted delivery of tumor antigens to DCs and prolong storage of cellular vaccines. Therefore, the development of other immunotherapeutic approaches capable of enhancing the immunogenicity of existing DC-based vaccines or directly triggering anti-tumor immune responses is of great interest. Extracellular vesicles (EVs) are released by almost all types of eukaryotic cells for paracrine signaling. EVs can interact with target cells and change their functional activity by delivering different signaling molecules including mRNA, non-coding RNA, proteins, and lipids. EVs have potential benefits as natural vectors for the delivery of RNA and other therapeutic molecules targeted to DCs, T-lymphocytes, and tumor cells; therefore, EVs are a promising entity for the development of novel cell-free anti-tumor vaccines that may be a favourable alternative to DC-based vaccines. In the present review, we discuss the anti-tumor potential of EVs derived from DCs, tumors, and other cells. Methods of EV isolation are systematized, and key molecules carried by EVs that are necessary for the activation of a DC-mediated anti-tumor immune response are analyzed with a focus on the RNA component of EVs. Characteristics of anti-tumor immune responses induced by EVs in vitro and in vivo are reviewed. Finally, perspectives and challenges with the use of EVs for the development of anti-tumor cell-free vaccines are considered.

Characteristics of in Vivo Model Systems for Ovarian Cancer Studies.

An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate the architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated in both the ovarian surface and tubal epithelium. It is postulated that clawed frog models could be developed, enabling studies on tumor immunity and anticancer immune response. In laying hen, ovarian cancer develops spontaneously, which provides the opportunity to study the genetic, biochemical, and environmental risk factors, as well as tumor initiation, progression, and histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows the study of drug response.

A Multi-million Mammography Image Dataset and Population-Based Screening Cohort for the Training and Evaluation of Deep Neural Networks\u2014the Cohort of Screen-Aged Women (CSAW)

For AI researchers, access to a large and well-curated dataset is crucial. Working in the field of breast radiology, our aim was to develop a high-quality platform that can be used for evaluation of networks aiming to predict breast cancer risk, estimate mammographic sensitivity, and detect tumors. Our dataset, Cohort of Screen-Aged Women (CSAW), is a population-based cohort of all women 40 to 74 years of age invited to screening in the Stockholm region, Sweden, between 2008 and 2015. All women were invited to mammography screening every 18 to 24 months free of charge. Images were collected from the PACS of the three breast centers that completely cover the region. DICOM metadata were collected together with the images. Screening decisions and clinical outcome data were collected by linkage to the regional cancer center registers. Incident cancer cases, from one center, were pixel-level annotated by a radiologist. A separate subset for efficient evaluation of external networks was defined for the uptake area of one center. The collection and use of the dataset for the purpose of AI research has been approved by the Ethical Review Board. CSAW included 499,807 women invited to screening between 2008 and 2015 with a total of 1,182,733 completed screening examinations. Around 2 million mammography images have currently been collected, including all images for women who developed breast cancer. There were 10,582 women diagnosed with breast cancer; for 8463, it was their first breast cancer. Clinical data include biopsy-verified breast cancer diagnoses, histological origin, tumor size, lymph node status, Elston grade, and receptor status. One thousand eight hundred ninety-one images of 898 women had tumors pixel level annotated including any tumor signs in the prior negative screening mammogram. Our dataset has already been used for evaluation by several research groups. We have defined a high-volume platform for training and evaluation of deep neural networks in the domain of mammographic imaging.

P13.05 Chemical Biopsy as an Alternative Sampling Method in Neurooncology

Abstract BACKGROUND Histopathology is a gold standard for diagnostics of brain tumors but it is time consuming, demands removal of the part of the tissue what makes it highly invasive. That is why it seems to be relevant to develop new diagnostic methods addressing the abovementioned drawbacks. Ideal tool should be easy to use, as low invasive as possible and of high clinical value. The aim of the study was to assess the usefulness of chemical biopsy based on solid phase microextraction as a sampling method for lipidomic analysis of brain tumors. MATERIAL AND METHODS The experiment was carried out on 38 brain tumors. Sampling was performed ex vivo, directly after removal of brain tumors. SPME fibers (coated with biocompatible extraction phase, length and diameter of the coating 7mm and 200um, respectively) were inserted into the sample without prior preparation of the tissue. Desorption of lipids was performed in isopropanol-methanol mixture. Analysis of extracts was carried out using liquid chromatography coupled to high resolution mass spectrometry. RESULTS Wide range of tentative lipid species was obtained in the studies. Two histologically different types of brain tumors: gliomas and meningiomas were subjected to the chemical biopsy. The results showed very good separation between the tumor types in unsupervised chemometric tests. The lipid species responsible for this separation were previously reported in the literature as cancer biomarkers. With regards to malignancy grading of gliomas the separation was notable but not as clear as between the tumor types, what is probably related to high heterogeneity of this cancerous tissue and subjectivity of histopathological analysis which were a referring point in methods comparison. Very good agreement was noted for changes in lipidome obtained by chemical biopsy and histological subtypes of gliomas. However, the most promising results showed impact of IDH1 R132H mutation on lipidome of gliomas. CONCLUSION Chemical biopsy seems to be useful method in lipidomics studies and for differentiation of brain tumors according their histological origin and malignancy. It also enables to find a relation between IDH1 mutation and lipidomic profile. ACKNOWLEDGMENTS The work was supported by the grant 2015/18/M/ST4/00059 funded by National Science Centre, Poland. The authors want to acknowledge Supelco/MilliporeSigma for the SPME probes, Thermo Fisher Scientific for the access to Q-Exactive Focus mass spectrometer, Anchem for the technical support and Shim-Pol for the access to LCMS-8060 mass spectrometer and technical support.

Promyelocytic Leukemia (PML) gene regulation: implication towards curbing oncogenesis

Dysregulation of PML, a significant tumor suppressor is linked with cancers of different histological origins, with a decreased expression observed with a higher tumor grade. This necessitates studying the mechanisms to maintain a stable expression of PML. However much less is known about the transcriptional regulation of PML, more so in the context of breast carcinoma. ERβ has emerged as a critical factor in understanding breast cancer, especially since a huge proportion of breast cancers are ERα− and thus insensitive to tamoxifen therapy. This study aims to uncover an unidentified mechanism of PML gene regulation and its stabilization in breast cancer via ERβ signalling and the impact on cellular apoptosis. We found that clinical expression of PML positively correlates with that of ERβ both in normal and breast carcinoma samples and inversely correlates with markers of cellular proliferation, hinting towards a possible mechanistic interdependence. Both mRNA and protein expression of PML were increased in response to ERβ overexpression on multiple human breast cancer cell lines. Mechanistically, luciferase reporter assays and chromatin-immunoprecipitation assays demonstrated that ERβ can interact with the PML promoter via ERE and AP1 sites to enhance its transcription. ERβ induced stable PML expression causes a decline of its target protein Survivin and simultaneously provides a stable docking platform leading to stabilisation of its target Foxo3a, further causing transcriptional upregulation of pro-apoptotic factors p21 and p27. Immunohistochemical analyses of cancer and normal breast tissues and functional assays conducted corroborated the findings. Collectively, our study identifies ERβ signalling as a novel mechanism for PML gene regulation in ERα− breast cancer. It also reveals bi-directional downstream effect in which ‘ERβ-PML-(Foxo3a/Survivin)’ network acts as a therapeutic axis by suppressing cellular survival and promoting cellular apoptosis in breast carcinoma.

LI-cadherin and CDX2: Useful Markers in Metastatic Gastrointestinal Adenocarcinoma Cells in Serous Cavity Effusion.

The aim of this study was to investigate the expression and significance of liver-intestine cadherin (LI-cadherin) and CDX2 (caudal-type homeobox transcription factor 2) in cytology specimens of metastatic gastrointestinal adenocarcinoma in serous cavity effusion. The serous cavity effusion samples that were suspected of tumor metastasis in the last 5 years were made into paraffin-imbedded cell blocks, a total of 180 cases, including 97 cases of pleural effusion, 78 cases of ascites, and 5 cases of pericardial effusion. The expressions of LI-cadherin and CDX2 were detected by immunohistochemical staining in cell blocks and primary tumor tissues; thereafter, the specificity and sensitivity were analyzed. The positive expressions of LI-cadherin and CDX2 in 63 cases of gastrointestinal adenocarcinoma cells were 65.1% (41/63), 61.9% (39/63), respectively. Of 11 cases of pancreaticobiliary duct cancers, only one case (9.09%) was weakly positive for LI-cadherin and CDX2 expressions, and 107 cases of non-digestive tract cancers were all negative. In 57 matched-pair samples of cell blocks and primary gastrointestinal adenocarcinoma tissues, the positive expressions of LI-cadherin and CDX2 were 64.9% (37/57), 61.4% (35/57), respectively, in cells, and 82.5% (47/57), and 77.2% (44/57), respectively, in tissues. Positive correlation was observed between the expressions of LI-cadherin and CDX2 in metastatic gastrointestinal adenocarcinoma cells (P<0.05). Both LI-cadherin and CDX2 expressions demonstrated positive correlation in cells with paired cancer tissues (P<0.05). The positive expression reached 80.7% with at least one positive marker in the total cell samples through combined detection of LI-cadherin and CDX2, increased by 15.8% and 19.3% compared with using either of the markers alone. Combined use of LI-cadherin and CDX2 can improve the accuracy in the diagnosis of metastatic adenocarcinoma cells in serous cavity effusion and provide some bases of histologic origin because of their high sensitivity and specificity.

CIITA-Driven MHC Class II Expressing Tumor Cells as Antigen Presenting Cell Performers: Toward the Construction of an Optimal Anti-tumor Vaccine.

Construction of an optimal vaccine against tumors relies on the availability of appropriate tumor-specific antigens capable to stimulate CD4+ T helper cells (TH) and CD8+ cytolytic T cells (CTL). CTL are considered the major effectors of the anti-tumor adaptive immune response as they recognize antigens presented on MHC class I (MHC-I) molecules usually expressed in all cells and thus also in tumors. However, attempts to translate in clinics vaccination protocols based only on tumor-specific MHC-I-bound peptides have resulted in very limited, if any, success. We believe failure was mostly due to inadequate triggering of the TH arm of adaptive immunity, as TH cells are necessary to trigger and maintain the proliferation of all the immune effector cells required to eliminate tumor cells. In this review, we focus on a novel strategy of anti-tumor vaccination established in our laboratory and based on the persistent expression of MHC class II (MHC-II) molecules in tumor cells. MHC-II are the restricting elements of TH recognition. They are usually not expressed in solid tumors. By genetically modifying tumor cells of distinct histological origin with the MHC-II transactivator CIITA, the physiological controller of MHC-II gene expression discovered in our laboratory, stable expression of all MHC class II genes was obtained. This resulted in tumor rejection or strong retardation of tumor growth in vivo in mice, mediated primarily by tumor-specific TH cells as assessed by both depletion and adoptive cell transfer experiments. Importantly these findings led us to apply this methodology to human settings for the purification of MHC-II-bound tumor specific peptides directly from tumor cells, specifically from hepatocarcinomas, and the construction of a multi-peptide (MHC-II and MHC-I specific) immunotherapeutic vaccine. Additionally, our approach unveiled a noticeable exception to the dogma that dendritic cells are the sole professional antigen presenting cells (APC) capable to prime naïve TH cells, because CIITA-dependent MHC-II expressing tumor cells could also perform this function. Thus, our approach has served not only to select the most appropriate tumor specific peptides to activate the key lymphocytes triggering the anti-tumor effector functions but also to increase our knowledge of intimate mechanisms governing basic immunological processes.

When hoofbeats mean zebras not horses: Tumour mimics of subdural haematoma – Case series and literature review

Chronic subdural haematomas are common neurosurgical conditions, especially in the elderly patients, with straightforward surgical treatments. However, infrequently, tumours are misdiagnosed as subdural haematoma on initial brain CT scans and are only discovered intraoperatively. In this case series, we presented 3 different patients who were initially thought to have subdural haematoma but later found to be tumour mimics of different histological origin. A literature review and discussion of recently published tumour mimics of subdural haematoma was also performed. It is recommended that in patients with suggestive oncological or haematological history, or unusual characteristics on the plain CT brain, a high level of suspicion of tumour mimics needs to be maintained. A full workup with contrast-enhanced magnetic resonance imaging is important to distinguish from subdural haematoma, as the treatment paradigms and prognoses are vastly different.

Clinicopathological features of minute meningothelial-like nodules in the lung

Objective To study the clinicopathological features of minute meningothelial-like nodule (MMLN) in the lung and its histological origin. Methods Clinicopathological data of 93 patients diagnosed with MMLN in Jiangsu Province Hospital(the First Affiliated Hospital of Nanjing Medical University) from September 2016 to September 2018 were collected and analyzed retrospectively, and the related literature was reviewed. Results Ninety-three MMLNs were identified from 5 239 patients undergoing pulmonary resection. There were 18(19.6%) males and 75(80.6%) females; age ranged 38-81 years, with mean age 58 years. The frequency of MMLNs was related to the site of origin, and single lesion most commonly (43%) arose in right lobe. There was no significant relationship with patients′ age, gender and the co-existing malignant tumors. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) was 0.584 (P<0.05), and the best cut-off point was 11.5, indicating an appropriate increase in the number of slides to at least 12 would facilitate the discovery of MMLN. Histologically, MMLN cells showed bland morphology, located around the normal alveolar cavity or form nests or whorls centered on small veins. Immunohistochemistry was done in 55 cases, and all cells expressed vimentin; and a high proportion of cells expressed EMA, PR, CD56 and Calponin. They were all negative for TTF1, Syn, CgA, CKpan, SMA and CD34. The Ki-67 index was low in all cases (<2%). In addition odds ratio analysis showed that MMLN was not a risk factor for invasive carcinoma (including other malignant tumors in the lung, P=0.100). Conclusions MMLN closely resembles meningothelioma morphologically and immunophenotypically, although its origin remains uncertain. In the study, MMLN is considered as a reactive benign lesion around pulmonary pathology, functioning as an effector regulating small blood vessels caliber. MMLN probably provides nutritional support to the surrounding disease and affords a suitable environment for the development of tumor cells. Key words: Lung diseases; Solitary pulmonary nodule; Minute meningothelial-like nodule

PLAC1: biology and potential application in cancer immunotherapy.

The emergence of immunotherapy has revolutionized medical oncology with unprecedented advances in cancer treatment over the past two decades. However, a major obstacle in cancer immunotherapy is identifying appropriate tumor-specific antigens to make targeted therapy achievable with fewer normal cells being impaired. The similarity between placentation and tumor development and growth has inspired many investigators to discover antigens for effective immunotherapy of cancers. Placenta-specific 1 (PLAC1) is one of the recently discovered placental antigens with limited normal tissue expression and fundamental roles in placental function and development. There is a growing body of evidence showing that PLAC1 is frequently activated in a wide variety of cancer types and promotes cancer progression. Based on the restricted expression of PLAC1 in testis, placenta and a wide variety of cancers, we have designated this molecule with new terminology, cancer-testis-placenta (CTP) antigen, a feature that PLAC1 shares with many other cancer testis antigens. Recent reports from our lab provide compelling evidence on the preferential expression of PLAC1 in prostate cancer and its potential utility in prostate cancer immunotherapy. PLAC1 may be regarded as a potential CTP antigen for targeted cancer immunotherapy based on the available data on its promoting function in cancer development and also its expression in cancers of different histological origin. In this review, we will summarize current data on PLAC1 with emphasis on its association with cancer development and immunotherapy.

Application of malignant pleural effusion cell blocks in the diagnosis and personalized treatment of advanced non-small cell lung carcinoma*

Abstract Objective The aim of the study was to investigate the efficacy of immunocytochemistry and related gene detection using cell block for the diagnosis and individualized treatment of advanced lung cancer. Methods Sixty-five malignant pleural effusion specimens were collected to make cell blocks, which were used for hematoxylin and eosin (H&amp;E) staining, immunocytochemical studies, and gene sequencing of the tumors to guide the individualized diagnoses and treatment of the given tumors. Results The tumor cells in the cell block sections were abundant in number with high quality cellular structures, and the histological morphological characteristics were partially maintained. Immunocytochemical staining was helpful in identifying the cell origin and tumor classification, and amplification refractory mutation system (ARMS) was used to determine the mutation status of epidermal growth factor receptor (EGFR). Of the 65 samples, 50 had a diagnosis of adenocarcinoma, 7 were pulmonary squamous cells, 6 were small cell carcinoma of the lung, and 2 were mesothelioma. The morphological features of the tumors were as follows: acinar formation, papillary and single cells for adenocarcinoma; intercellular bridges for squamous cell carcinoma; and morphology of the small cells is similar to that of the smear. Correlating with the results of immunocytochemical staining and clinical data analysis, 40 cases were confirmed as pulmonary adenocarcinoma, with an additional 4 cases of breast cancer, 3 cases of ovarian adenocarcinoma, and 3 cases of colorectal adenocarcinoma. Of the 47 non-small cell lung carcinoma (NSCLC) patients, EGFR mutations were detected in 26 cases (55.3%) by ARMS, with four mutation types: exon 19 deletion (13 cases, 50.0%), exon 2l point mutations L858R (11 cases, 42.3%) and L861Q (1 case, 3.8%), and exon 18 point mutation G719X (1 case, 3.8%). Conclusion Malignant pleural effusion cell blocks combined with immunocytochemical markers and molecular pathology are helpful for the diagnosis of advanced tumors, the identification of tumor properties and histological tumor origin, and the selection of individualized treatment for advanced lung cancer.

Machine learning algorithm analysis using a commercial 592-gene NGS panel to accurately predict tumor lineage for carcinoma of unknown primary (CUP).

3083 Background: The diagnosis of a malignancy is typically informed by clinical presentation and tumor tissue features including cell morphology, immunohistochemistry, cytogenetics, and molecular markers. However, in approximately 5-10% of cancers, ambiguity is high enough that no tissue of origin can be determined and the specimen is labeled as a Cancer of Occult\Unknown Primary (CUP). Lack of reliable classification of a tumor poses a significant treatment dilemma for the oncologist leading to inappropriate and/or delayed treatment. Methods: 40,000 tumor patients with NGS data were used to construct a multiple parameter lineage-specific classification system using an advanced machine learning approach. The dataset for each classifier was split 50% for training and the other 50% for testing. The training task for each classifier was to identify the cases that were similar to the cases it was trained on against a backdrop of randomly selected cases of other histological origins. Results: Tumor lineage classifiers predicted the correct classifications where the primary site was known with accuracies ranging between 85% and 95%. When applied to CUP cases (n = 500), an unequivocal result could be obtained 100% of the time. Conclusions: Lineage predictors can render a histologic diagnosis to CUP cases that can inform treatment and potentially improve outcomes.

Study of cervical cancer through fractals and a method of clustering based on quantum mechanics

Tumor growth in the cervix is a complex process. Understanding this phenomena is quite relevant in order to establish proper diagnosis and therapy strategies and a possible startpoint is to evaluate its complexity through the scaling analysis, which define the tumor growth geometry. In this work, tumor interface from primary tumors of squamous cells and adenocarcinomas for cervical cancer were extracted. Fractal dimension and local roughness exponent (Barabási and Stanley (1996)), αloc, were calculated to characterize the in vivo 3-D tumor growth. Image acquisition was carried out according to the standard protocol used for cervical cancer radiotherapy, i.e., axial, magnetic resonance T1 - weighted contrast enhanced images comprising the cervix volume for image registration. Image processing was carried out by a classification scheme based on quantum clustering algorithm (Mussa et al. (2015)) combined with the application of the K-means procedure upon contrasted images (Demirkaya et al. (2008)). The results show significant variations of the parameters depending on the tumor stage and its histological origin.

In Vitro Evaluation of Chitosan Induced Cytotoxicity against Cancerous Cell lines: MCF-7, Saos-2 and HeLa

Objective/ Background: Cancer is still the most common cause of morbidity in world and new powerful anticancer agents without severe side effects from natural sources is important. Methods: The evaluation of cytotoxicity and apoptosis induction was carried out in MCF-7,HeLa and Saos-2 as cancerous cell lines with different histological origin and human fibroblast served as control normal cell. The cells were treated with different concentrations of chitosan and the cytotoxicity was determined using MTT assay after 24, 48 and 72 h .The mode of death was evaluated by flow cytometry . Results: While both types of chitosan showed significant concentration-dependently cytotoxic effects against the three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. On the other hand, there were no significant differences between LMWC and HMWC cytotoxicity in all cell lines. The flow cytometry results showed the apoptosis pattern of death more in Saos-2 and HeLa while necrosis was more observable with MCF7. Also higher viability with both types of chitosan was seen in fibroblast as normal cells Conclusion: Chitosan shows anticancerous effect against 3 cancerous cell lines, while it is compatible with normal diploid fibroblast cells. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property.

Flavonoids and the Risk of Gastric Cancer: An Exploratory Case-Control Study in the MCC-Spain Study.

Several epidemiological studies have investigated the association between the dietary flavonoid intake and gastric cancer (GC) risk; however, the results remain inconclusive. Investigating the relationship between the different classes of flavonoids and the histological types and origin of GC can be of interest to the research community. We used data from a population-based multi-case control study (MCC-Spain) obtained from 12 different regions of Spain. 2700 controls and 329 GC cases were included in this study. Odds ratios (ORs) were calculated using the mixed effects logistic regression considering quartiles of flavonoid intakes and log2. Flavonoid intake was associated with a lower GC risk (ORlog2 = 0.76; 95% CI = 0.65–0.89; ORq4vsq1 = 0.60; 95%CI = 0.40–0.89; ptrend = 0.007). Inverse and statistically significant associations were observed with anthocyanidins, chalcones, dihydroflavonols and flavan-3-ols. The isoflavanoid intake was positively associated with higher cancer risk, but without reaching a statistical significance. In general, no differences were observed in the GC risk according to the location and histological type. The flavonoid intake seems to be a protective factor against GC within the MCC-study. This effect may vary depending on the flavonoid class but not by the histological type and location of the tumor. Broader studies with larger sample size and greater geographical variability are necessary.

Surgical management and outcome of intramedullary spinal cord tumour

ObjectiveOur aim is to assess the surgical management of intramedullary spinal cord tumours (IMSCTs) and evaluate factors associated with surgical outcomes in our hospitals.Patient and methodsBetween June 2013 and June 2016, a retrospective study was conducted on 16 consecutive cases of IMSCTs. All patients provided their signed consent, and MRI was performed. The patients were surgically treated and were evaluated pre- and post-operatively by the modified McCormick scale (MMS). Appropriate statistical analysis was conducted.ResultsThe mean patient age was 50.4 years, and the median follow-up was 15 months. The most common histological origin was ependymoma (n = 9, 56.25%). A cervical tumour was detected in eight patients, and a dorsal tumour was detected in seven. Post-operatively, the score was clinically but not statistically improved in seven cervical (87.5%) and four dorsal (57.1%) tumours (p = 0.334). Ten patients underwent total resection. Post-operative MMS scores showed improvement in all cases of total resection (n = 10, 100%). This improvement was clinically and statistically significant on last follow-up (p = 0.008). Fewer than four segments were involved in 9 cases, and more than four segments were involved in 7 cases. Post-operatively, all 9 patients (100%) with fewer than four involved segments improved, while only three patients (42.9%) with more than 4 involved segments improved (p = 0.019). Low-grade tumours such as ependymomas were correlated with good surgical outcomes, while high-grade tumours such as astrocytomas were correlated with poor surgical outcomes (p = 0.022).ConclusionsTotal tumour resection coupled with good preoperative clinical condition for tumours localised in the cervical or conus region predicts good neurological outcomes. Tumour localisation in the dorsal region with multi-segmental extension and high-grade tumour pathology predicts poor neurological outcomes.

Informações aos pais: um subsídio ao enfrentamento do câncer infantil

O número de casos de câncer tem aumentado nas últimas décadas, convertendo-se em um problema de saúde pública mundial, devido às altas incidência e mortalidade, além de suas implicações na qualidade de vida do sujeito e de sua família. Cânceres pediátricos apresentam particularidades em relação a tumores que acometem adultos, como diferentes locais primários e distinta origem histológica, além de um menor período de latência, o que implica em um crescimento mais rápido e maior capacidade de invasão de tecidos adjacentes. Entretanto, respondem melhor ao tratamento quimioterápico. O objetivo do trabalho foi descrever, do ponto de vista dos pais, o processo de comunicação do diagnóstico e tratamento da criança, identificar as dúvidas dos mesmos e analisar como tais informações influenciaram a família no enfrentamento da doença. Foi realizada pesquisa qualitativa descritiva com 19 pais de crianças em tratamento quimioterápico em um Hemocentro do Paraná. A coleta de dados deu-se nos meses de julho e agosto de 2014 por meio de entrevista semiestruturada. Adotou-se para análise dos dados a Análise de Conteúdo Temática. Entre as percepções dos pais sobre o esclarecimento da doença emergiram três temas: processo de comunicação do diagnóstico e formas de tratamento; informações: algumas recebidas, outras obtidas; informações como subsídio para o cuidado. A pesquisa revelou a necessidade de reconhecer a díade criança-família como paciente, para que os pais obtenham informações concretas sobre o diagnóstico e tratamento a fim de utilizá-las como subsídio para o enfrentamento e empoderamento.