Tissue Tumors Research Articles

Evolution of the Solid Human Tumor Cells Properties in Various Experimental Systems in Vitro

Background Human malignant cell models which reflect the structural and physiological complexity of tumor tissue are of great importance for preclinical research in oncology. Spheroids/tumoroids derived from solid tumors are of great interest as cellular models mimicking the first vascular-free growth phase of a tumor node. The fact of the identity between artificially created tumor multicellular aggregates and the real tumor tissue, however, needs to be specified, described and validated in order to see how closely the spheroids are biologically similar to the malignized tissues in vivo compared to the monolayer cell cultures traditionally used. We present here a comparison study of the characteristics of solid tumor cells of different histogenesis (melanomas, soft tissue sarcomas and bone sarcomas, epithelial tumors) cultured in two dimensions (monolayer culture) and three dimensional space (spheroid), namely: spatial organization, multiplication, metabolic activity. Patients and Methods For the creation of 2 D and 3D cell models the cells isolated from the patient's solid tumor fragments obtained intraoperatively were used. 15 samples of skin melanoma, 20 samples of soft tissue and osteogenic sarcomas (STBS), and 9 samples of epithelial tumors (ET). The tumor cells were all cultivated for at least 10 passages. We used phase contrast, confocal microscopy, and immunohistochemistry to investigate spheroids and monolayer cultures. The supernatants of tumor cells grown in 2D and 3D cultures were studied using ELISA and multiplex analysis for the production of a spectrum of chemokines and cytokines supporting the immunosuppression, invasion and metastasis processes. Results Tumor specimens received were predominantly of metastatic origin (75%). In 100% of cases 2D cultures were received, in 88.6% of cases (39 out of 44) we succeeded in obtaining spheroids. There was no direct correlation between the efficiency of tumoroid formation and the tumor's histogenetic origin and the stage of the cancer process (primary tumor, recurrence, metastasis). The median size of spheroids by 4-5 days of cultivation with a starting concentration of 10000 cells per well was 657.14 μm for melanoma (min 400 - max 1000 μm), 571.42 μm (min 400 - max 700 μm), 507.14 μm (min 300 - max 600 μm) for soft tissue sarcomas, 650.0 μm (min 400 - max 900 μm) for osteogenic sarcomas. Immunochemical analysis of Ki-67, GLUT1, and Ecadherin markers was carried out for tumor tissue samples, single-layer tumor cultures, and tumoroids of every patient. The distribution of the stained groups in the spheroids was distinct from the monolayer cultures and more in accordance with the distribution of such in the tissue tumor, the number of Ki-67+ cells was increasing in the spheroids. We detected no dependence of Ki-67+ and GLUT1+ cell localization grade on spheroid size. We identified E-cadherin in tumor tissue and tumoroids of breast carcinoma and one melanoma culture. Monolayer cultures did not express it. The increase in secretory cell activity of the solid tumor cells from 2D to 3D system was observed when CCL2, CCL3, CXCL1, CXCL16, MIF, IL10, MICA (p<0.01) were investigated. Conclusion The presence of patient-specific cells of solid tumors in a 3D environment causes activation of the proliferative and metabolic processes as compared to monolayer cultures, which makes these models approximate the real world clinical picture. The production of chemokines that can attract to the tumor various types of immune system cells, to include their immature versions, as well as production of cytokines and Immunosuppression factors that, when present in the tumor microenvironment in the high concentrations, contribute to the formation of immune cells having suppressive capacities occurs in the 3D cell system. Three-dimensional model of the initial tumor nodule formation stage thus demonstrates the forming process of tumor cells favorable for them microenvironment. Construction of three-dimensional models - spheroids of tumor cells of differing histogenesis demands individual approach and more thorough investigation

Real-Time, Multicolor Fluorescence Imaging of Tumors in Tissues

Novel synthetic fluorescent dyes in combination with shortwave infrared irradiation allow the high-resolution imaging of tissues within living organisms and can overcome several limitations of existing techniques in terms of penetration depth. Furthermore, they enable the simultaneous visualization of multiple tissue types and processes, making it possible to distinguish tumors from surrounding tissues.

PRINCIPLES OF DIAGNOSIS AND TREATMENT OF ASKIN’S TUMOR IN CHILDREN: CASE REPORT

The aim of the study was to show principles of diagnosis and treatment of Askin’s tumor in children. Diagnostic procedures include physical examination, chest X-ray, CT scan and PET CT, morphological, histological and immunohistochemical examinations, cytogenetic study. Primitive neuroectodermal tumors belong to the group of low differentiated, overly aggressive neoplasms, originating from cells of the parasympathetic autonomic nervous system. Patient F., 9 years old, first consulted by pediatric oncologist in 2014 with complaints of volume formation in the chest on the right side which progressively increases. Diagnosis: PNEP (primitive neuroectodermal tumor) of the soft tissues of the chest on the right side in the 4th intercostal space along the midclavicular line T2aN0M0, stage 2a, standard risk group. We’ve shown results of diagnostical process, treatment and it’s result in our patient. Patients who have received combination therapy, including chemotherapy, surgical removal of the tumor and radiation therapy, have better prognostic results. However, relapses often occur that require more aggressive treatment with high-dose chemotherapy, monoclonal antibodies, and bone marrow transplantation.

The Prognostic Value of Cancer Stem Cell Markers in Cervical Cancer: A Systematic Review and Meta-Analysis.

Objectives:Prognostic biomarkers in cervical cancer are widely investigated, including cancer stem cell (CSC) markers. However, their significance remains uncertain. This study aimed to determine the role of cervical cancer stem cell (CCSC) markers for survival. Materials and Methods:We conducted a systematic review and meta-analysis (PROSPERO CRD42021237072) of studies reporting CCSC markers as the prognostic predictor based on PRISMA guidelines. We included English articles investigating associations of CCSCs expression in tissue tumor with overall survival (OS) or disease-free survival (DFS) from PubMed, EBSCO, and The Cochrane Library databases. The quality of studies was analyzed based on Newcastle-Ottawa Quality Assessment Scale. Results:From 413 publications, after study selection with inclusion and exclusion criteria, 22 studies were included. High expressions of CCSC markers were associated with poor OS and DFS (HR= 1.05, 95% CI: 1.03 – 1.07, P <0.0001; HR= 1.31, 95% CI: 1.09 – 1.17, P <0.00001; respectively). Sub-analysis of individual CCSC markers indicated significant correlations between CD44 (HR= 1.14, 95% CI: 1.07 – 1.22, P 0.0001), SOX2 (HR= 1.58, 95% CI: 1.17 – 2.14, P 0.003), OCT4 (HR= 1.03, 95% CI: 1.01 – 1.06, P 0.008), ALDH1 (HR= 1.36, 95% CI: 1.13 – 1.64, P 0.001), and CD49f (HR= 3.02, 95% CI: 1.37 – 6.64, P 0.006) with worse OS; OCT4 (HR= 1.14, 95% CI 1.06 – 1.22, P 0.0003), SOX2 (HR= 1.11, 95% CI: 1.06 – 1.16, P <0.0001), and ALDH1 (HR= 1.22, 95% CI: 1.10 – 1.35, P 0.0002) with poor DFS. We did not conduct a meta-analysis for MSI-1 and CK17 because only one study investigated those markers. Conclusion:Expressions of OCT4, SOX2, and ALDH1 were associated with poor OS and DFS in cervical cancer tissue. These markers might have potential roles as prognostic biomarkers to predict unfavorable survival.

Rare benign tumor in a prepubescent accessory breast: a case report

BackgroundPolymastia or accessory breast is a congenital condition seen in 1% of the population at birth and in 2–6% of the female population. The most common presentation is in the pubertal age group when secondary sexual characters begin to develop or during pregnancy and lactation. Giant cell fibroblastoma is an exceedingly rare benign soft tissue neoplasm in the pediatric age group, usually seen over the back and thigh. We report a case of giant cell fibroblastoma in accessory breast tissue in a 4-year-old, female child. This case is rare in its presentation at the age of 4 years with an enlarging accessory breast without any secondary sexual characters. Giant cell fibroblastoma in the accessory breast tissue is unreported yet.Case presentationA 4-year-old female child presented with a progressively enlarging accessory breast. A wide local excision of the accessory breast with underlying growth was done. The histopathological examination revealed a giant cell fibroblastoma within the breast tissue.ConclusionsEnlargement of an accessory or normal breast at a prepubescent age with the absence of secondary sexual characters should arouse suspicion of benign tumors in the breast tissue.

Presentation and management of pheochromocytomas and paragangliomas: about 40 cases

BackgroundPheochromocytoma and paraganglioma are rare neuroendocrine tumors of the chromaffin tissue, which may produce catecholamines. The aim of our study was to analyze the clinical and para-clinical aspects as well as the therapeutic and evolutionary aspects of pheocromocytomas and paragangliomas based on a series of 40 cases.MethodsOur retrospective population-based research study includes 40 patients. Then, a statistical analysis was carried out using the SPSS software (version21).ResultsOur study involves 40 patients, including 23 women (57, 5%) and 17 men (42,5%). The mean age at the time of the diagnosis was 43.8 ± 16.8 years. The circumstances of the discovery were mainly characterized by adrenal incidentaloma and hypertension. The biological diagnosis was based on the dosage of urinary metanephrines and plasma-free metanephrines in, respectively, 61.5% and 18% of cases. A computerized tomography scan and/or a magnetic resonance imaging scan could help to locate the tumor in 100% of cases. Our series includes 3 cases of bilateral pheochromocytoma, 3 cases of paragangliomas and 1 case of malignant pheochromocytoma, while a hereditary form was retained in 3 patients. In fact, thirty-two patients were operated; cure was clinically labeled in 100% and biologically in 87.5% of patients.ConclusionsThe main points for improvement that our study has revealed are; a patient follow-up after surgery, which was not always regular, and an insufficient screening for genetic diseases associated with pheochromocytomas and paragangliomas.

DNA methylation-based prognostic subtypes of chordoma tumors in tissue and plasma.

Chordomas are rare malignant bone cancers of the skull-base and spine. Patient survival is variable and not reliably predicted using clinical factors or molecular features. This study identifies prognostic epigenetic chordoma subtypes that are detected noninvasively using plasma methylomes. Methylation profiles of 68 chordoma surgical samples were obtained between 1996 and 2018 across three international centers along with matched plasma methylomes where available. Consensus clustering identified two stable tissue clusters with a disease-specific survival difference that was independent of clinical factors in a multivariate Cox analysis (HR = 14.2, 95%CI: 2.1-94.8, P = 0.0063). Immune-related pathways with genes hypomethylated at promoters and increased immune cell abundance were observed in the poor-performing "Immune-infiltrated" subtype. Cell-to-cell interaction plus extracellular matrix pathway hypomethylation and higher tumor purity were observed in the better-performing "Cellular" subtype. The findings were validated in additional DNA methylation and RNA sequencing datasets as well as with immunohistochemical staining. Plasma methylomes distinguished chordomas from other clinical differential diagnoses by applying fifty chordoma-versus-other binomial generalized linear models in random 20% testing sets (mean AUROC = 0.84, 95%CI: 0.52-1.00). Tissue-based and plasma-based methylation signals were highly correlated in both prognostic clusters. Additionally, leave-one-out models accurately classified all tumors into their correct cluster based on plasma methylation data. Here, we show the first identification of prognostic epigenetic chordoma subtypes and first use of plasma methylome-based biomarkers to noninvasively diagnose and subtype chordomas. These results may transform patient management by allowing treatment aggressiveness to be balanced with patient risk according to prognosis.

Neuropsychological features of patients of reproductive age diagnosed with breast cancer at the stage of surgical treatment using xenon-oxygen therapy

Purpose of the study. To study functional changes in the neuropsychological status of reproductive age patients with newly diagnosed breast cancer and to assess the possibility of using xenon-oxygen therapy to correct disorders.Patients and methods. This study included 60 reproductive age patients with newly diagnosed breast cancer who were undergoing surgical treatment at the Department of Bone, Skin, Soft Tissue and Breast Tumors of the National Medical Research Centre for Oncology of the Ministry of Health of Russia from 2018 to 2020. The main group included 30 patients with breast cancer diagnosed at the surgical stage of combined treatment, who underwent a rehabilitation course of xenon-oxygen therapy in the early postoperative period. The control group was formed from patients with the same diagnosis, without the use of this therapy. The functional state of the central nervous system in all patients was assessed by the parameters of the electroencephalography (EEG) bioelectrical activity. For the final assessment of the physiological and psychological state of the patients, a standardized questionnaires of the quality of life – ESAS, MOS-SF‑36, were used. Statistical data processing was performed using the Statistica 10 software package. Results. During the study, statistically significant differences were found in the assessment of subjective indicators, so in the group of patients using xenon-oxygen therapy, there was an improvement in well-being by 2.6 times, a decrease in depression by 2.3 times, a decrease in symptoms of nausea by 3 times, anxiety 1.9 times (p &lt; 0.05). Against the background of an improvement in the psychophysiological state, the EEG showed a significant increase in the power of slow delta and theta rhythms, an increase in the power of the alpha rhythm and a decrease in the power of the beta rhythm, while in the patients of the control group only a decrease in the power of the beta rhythm was noted.Conclusion. The early postoperative period in patients with newly diagnosed breast cancer is characterized by the formation of a depressive symptom complex. The use of a course of xenon-oxygen therapy contributes to the normalization of the subjective feeling of physical and psychological health, increasing vital and social activity. Changes in the indicators of brain bioelectric activity and an improvement in psychophysiological state occur against the background of changes in brain activity caused by the normalizing effect of xenon.

Axillary Mass Turned Out to be A Phyllodes Tumour in An Ectopic Breast Tissue– A Rare Case Report

Background: Phyllodes tumours are rare fibroepithelial lesions that account for less than 1% of all breast neoplasm. However, phyllodes tumours arising from ectopic breast tissue are even rarer, with less than 15 cases ever reported involving the axilla, vulva and groin. Case Presentation: A 27-year-old lady presented to the surgical clinic with left axillary swelling, measuring 5cm x 6cm. Ultrasound of the axilla revealed heterogenous mass displacing the left axillary artery and vein medially. Excision was performed, and histopathological examination confirmed the diagnosis of a benign phyllodes tumour. Conclusion: Phyllodes tumour in ectopic breast tissue over the axilla is a rare occurrence, and our case is the fourth case ever reported. Despite its rarity, diagnosis and treatment modalities are similar to phyllodes tumour of the breast. Regular follow-up is recommended owing to the risk of local recurrence.

Abstract 2202: Genetic characterization of metastasis and prognosis in high-grade serous ovarian cancer

Abstract High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and is highly prone to metastasis, with the majority of patients presenting at advanced stages of disease. There are few targeted treatment options for HGSC patients, especially for women with high metastatic tumor burdens. In order to identify potential genetic targets in metastatic disease, we characterized the genomic and transcriptomic alterations of metastatic tumors in HGSC patients. In this study, matched normal tissue, primary, and metastatic tumors from 23 HGSC short-term (ST) survivors (overall survival [OS] &amp;lt;3.5 years) and 14 long-term (LT) survivors (OS &amp;gt;5 years) underwent whole exome and RNA sequencing. We compared somatic mutations, copy number alternations, mutational burdens, differential expression, immune cell fractions, and gene fusion predictions between the primary and metastatic tumors of the ST and LT survival groups. We confirmed that tumors of LT survivors were more likely to have BRCA1 alterations and more copy-altered segments when compared to tumors of ST survivors. There was a higher percentage of shared variants between the primary and metastatic tumors for ST survivors compared to LT survivors. ST survivors also had a greater mutational burden and more predicted gene fusions than LT. We observed few differentially expressed genes between primary and metastatic tumors, but we did observe significant differences between the transcriptomes of LT and ST survivors' tumors. Overall, we observed that HGSC primary and metastatic tumors had similar genomic and transcriptomic landscapes, but we identified genetic characteristics specific to metastatic tumors that correlate with survival. Citation Format: Emilee N. Kotnik, Nicholas C. Spies, Tiandao Li, Matthew Inkman, Jin Zhang, Fernanda Martins-Rodrigues, Ian S. Hagemann, Carolyn K. McCourt, Premal H. Thaker, Andrea R. Hagemann, Matthew A. Powell, David G. Mutch, Christopher A. Maher, Christopher A. Miller, Katherine C. Fuh. Genetic characterization of metastasis and prognosis in high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2202.

Abstract 1304: AbYlinkTM: A site-selective labeling method for preclinical imaging of therapeutic antibodies

Abstract Clinical development of therapeutic antibodies relies on robust and thorough preclinical evaluation of multiple pharmacodynamic and pharmacokinetic parameters of antibody candidates. While current methods are available for in vitro characterization of antibodies, in vivo determination of tissue distribution, tumor accumulation and retention and potential off-target effects cannot be performed non-invasively in vivo over a prolonged period of time. Here, we used AbYlinkTM, a novel site-selective labeling method of native antibodies, enabling the single-step covalent conjugation of a radionuclide chelator to the Fc domain of any IgG antibody isotype. Given the selectivity of this reaction for the Fc region of the immunoglobulin, labeling of the antibody at this location should not compromise binding to the antigen. Chelators that are covalently attached to the antibody allows for the labeling with radioisotopes such as 68Ga, 177Lu, 111In and 89Zr, and for the sensitive and quantitative molecular in vivo measurement by Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT). AbYlinkTM also permits the conjugation of fluorescent dyes to antibodies with the aim to measure antibody pharmacodynamic parameters by intravital microscopy. In this work, we have validated the technology by labeling several antibodies and ADCs with different payloads. Importantly, antibodies conjugated with AbYlinkTM retained the same affinity to the antigen as the original, unconjugated antibodies, contrary to the randomly labelled antibodies. We will also present data on the specific radiolabeling of commercially available trastuzumab with 111Indium and the SPECT images obtained after injection of mice bearing HER2-positive tumors with 111In-trastuzumab. The present data suggest that AbYlinkTM can be used to support preclinical drug discovery tools to assist in the selection of therapeutic antibody candidates and/or for pharmacodynamic assessment of commercial antibodies. Furthermore, the specificity of the chemical conjugation suggests that AbYlinkTM can help to control the chelator distribution on the antibody drug conjugates. Citation Format: Viktoriia Postupalenko, Léo Marx, David Viertl, Natalia Gasilova, Mathilde Plantin, Nadège Gsponer, Alexandre Johanssen, Thibaut Denoel, Gerrit Hagens, Jean-Manuel Segura, Frédéric Levy, Patrick Garrouste, John Prior, Margret Schottelius, Niklaus Schaefer, Origene Nyanguile. AbYlinkTM: A site-selective labeling method for preclinical imaging of therapeutic antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1304.

Abstract 905: Investigating the effects of aerobic exercise on preclinical breast cancer outcomes

Abstract Aerobic exercise is receiving increased recognition in oncology spheres for its multiple purported benefits. Exercise is known to induce physiologic responses that improve patient quality-of-life parameters as well as all-cause mortality. There is also a growing body of evidence that suggests exercise may directly impact tumor biology and therapy outcomes. Previous studies suggest that exercise can improve tumor perfusion and ameliorate intratumoral hypoxia, increase recruitment of cytotoxic immune cells, and alter metabolic substrate availability. Furthermore, the physiologic adaptations to exercise in normal tissue may protect against treatment-associated toxicity and allow for greater treatment tolerance. With regard to cancer metastasis, reports have been conflicting. The goal of this study was to characterize the effect of exercise on normal tissue adaptations, tumor microenvironment, metastasis, and doxorubicin cardiotoxicity in preclinical breast cancer models. Female, retired breeder BALB/c mice were employed, and aerobic exercise was modeled by singly-housing mice with access to wireless, low-profile voluntary running wheels. Sedentary controls were singly housed with plastic huts. Syngeneic 4T1 or EMT6 breast adenocarcinoma cells were inoculated either intraductally into the 4th mammary duct or intravenously into the tail-vein. In one study, doxorubicin was administered via 3 intraperitoneal (IP) injections over 7 days for a total dose of 11 mg/kg. Exercising mice steadily increased the amount they ran until they reached a plateau of 10-12 km/day from day 10 onward. This exercise regime induced cardiac hypertrophy and oxidative phenotypes in the quadriceps muscle relative to non-wheel running controls. It also prevented the cardiac atrophy and bodyweight loss induced by doxorubicin treatment. In mice bearing intraductal EMT6 tumors, exercise delayed tumor growth and improved survival relative to non-wheel running controls. However, exercise did not alter 4T1 tumor growth or survival. The effect of exercise on metastasis was assessed under three conditions, 1) in mice that ran before and after intravenous 4T1 cell injection, 2) mice that had limited (low exercise) or full (high exercise) access to running wheels after intravenous 4T1 cell injection, and 3) mice than ran after intraductal 4T1 cell injection. Under all three conditions, exercise did not affect the establishment of pulmonary macro-metastases. Taken together, these data suggest that while aerobic exercise may impact tumor growth and metastasis only in some tumor models, the normal tissue adaptations induced by exercise can be sufficient to protect against chemotherapy toxicity, thus warranting further studies of this modality in oncology settings. Citation Format: Zachary Richard Wakefield, Mai Tanaka, Angela Bundy, Sharon Lepler, Christine Pampo, Lori Rice, Dietmar W. Siemann. Investigating the effects of aerobic exercise on preclinical breast cancer outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 905.

UCP-2 inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells

PurposeThis study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment.Methods32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab.ResultsUCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis.ConclusionTaken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.

LIQUID NITROGEN CRYOSURGERY FOR CUTANEOUS AND OCULAR NEOPLASMS IN KOI (CYPRINUS CARPIO) AND GOLDFISH (CARASSIUS AURATUS): EIGHT CASES (2018-2019).

Cryosurgery, also known as cryotherapy and cryoablation, is a promising surgical technique that employs highly localized freezing to destroy damaged and diseased tissue, including benign and malignant neoplasms. This procedure has been reported in the treatment of chromatophoromas, fibromas, and peripheral nerve sheath tumors in piscine patients. This study presents eight clinical cases of cryosurgery on cyprinid pet fish for a wide array of neoplastic masses, including chromatophoromas, squamous cell carcinoma, and sarcomas that were diagnosed by histopathology. Surgical excision of external masses, liquid nitrogen cryotherapy, injectable medications (meloxicam and danofloxacin), and topical medical-grade honey were applied to the patients after biopsy sampling. Five out of seven cutaneous cases and two out of three ocular cases had complete resolution without recurrence for at least three months posttreatment. Treatment was unsuccessful for two of the cutaneous cases in which the cutaneous masses were extremely invasive, resulting in severe ulceration and deep invasion into the coelomic cavity. One of the ocular cases involved a corneal mass that did not change in size and had no complications after treatments, suggesting that the treatment might be useful in limiting growth. The effectiveness of cryotherapy appears to correlate with the tumor type, as well as the stage and progression of tumor invasion.

Giant axillary lipoblastoma in an African child: a case report

BackgroundLipoblastoma is a rare benign neoplasm of the adipose tissue occurring most commonly in infants and young children. This tumor can present as a localized, well-circumscribed lesion (lipoblastoma) or as a multi-centric lesion (lipoblastomatosis).Case presentationThis is a case report of lipoblastoma in a 19-month-old male with 9 months history of rapidly progressing axillary mass. Examination revealed a well-circumscribed right axillary mass measuring 25 cm × 20 cm with normal overlying skin and prominent, visibly distended superficial veins. He had surgical excision of the mass. Histologic examination revealed lipoblastoma. There has been no recurrence in the last 21 months of follow-up.ConclusionThe report is presented for its rarity and also for its potential to pose diagnostic difficulty to surgeons. Surgical excision offers the best chance of cure. Long-term follow-up is also important to detect recurrence.

Rapid brain structure and tumour margin detection on whole frozen tissue sections by fast multiphotometric mid-infrared scanning

Frozen section analysis is a frequently used method for examination of tissue samples, especially for tumour detection. In the majority of cases, the aim is to identify characteristic tissue morphologies or tumour margins. Depending on the type of tissue, a high number of misdiagnoses are associated with this process. In this work, a fast spectroscopic measurement device and workflow was developed that significantly improves the speed of whole frozen tissue section analyses and provides sufficient information to visualize tissue structures and tumour margins, dependent on their lipid and protein molecular vibrations. That optical and non-destructive method is based on selected wavenumbers in the mid-infrared (MIR) range. We present a measuring system that substantially outperforms a commercially available Fourier Transform Infrared (FT-IR) Imaging system, since it enables acquisition of reduced spectral information at a scan field of 1 cm2 in 3 s, with a spatial resolution of 20 µm. This allows fast visualization of segmented structure areas with little computational effort. For the first time, this multiphotometric MIR system is applied to biomedical tissue sections. We are referencing our novel MIR scanner on cryopreserved murine sagittal and coronal brain sections, especially focusing on the hippocampus, and show its usability for rapid identification of primary hepatocellular carcinoma (HCC) in mouse liver.

Racial disparities in pediatric cancer care in the United States: An analysis of the Kids' Inpatient Database.

10016 Background: The impact of race and socioeconomic status (SES) on cancer mortality has been elucidated in adult patients, but is not well described in pediatric oncology. We hypothesize that racial and socioeconomic disparities exist in pediatric cancer patients, resulting in higher rates of hospitalization and mortality. Methods: We analyzed the Kids’ Inpatient Database (KID) which shows national estimates of inpatient stays for pediatric patients. Inclusion criteria included patients who were ≤20 with a cancer diagnosis identified through the Clinical Classifications Software (CCS). Variables analyzed were discharge status, patient demographics, hospital characteristics, expected payment source, total visit charge, and length of stay. Initial comparisons between cancer and non-cancer related discharges were performed using a chi-square test. To estimate disparities by race, clinical comparisons were performed across five racial groups: White, Black, Hispanic, Asian/Pacific Islander, and Native American/Other. A multivariable logistic regression model was used to examine predictors of hospitalization and mortality. Results: From 2006-2012, there were 9,488,477 non-cancer related pediatric inpatient stays and 242,489 cancer related stays. Patients with cancer related visits were more likely to be white, male (54.9% vs 46.1%, p &lt; 0.0001), older at admission, have private insurance (52.5% vs 41.7%), and were from a higher income quartile (76th-100th percentile, 25.2% vs 19.9%, p &lt; 0.001). These patients also had a higher rate of death during admission (1.2% vs 0.5%, p &lt; 0.0001), higher cost of visit charge ($25,097 vs $8,267, p &lt; 0.001), longer length of stay (4 vs 2 days), and were less likely to be discharged (85.5% vs 92.0%, p &lt; 0.0001).The four most frequent cancer diagnoses associated with hospital admission were leukemia (n = 75,807), Other and Unspecified Primary (n = 50,076), bone/connective tissue tumor (n = 42,477), and central nervous system tumor (n = 27,958). Patients who were non-white were more likely to die during their inpatient stay (1.5% Non-white versus 0.9% White, p &lt; 0.001). On multivariate logistic regression, Black (OR: 1.61, 95% CI: 1.57-1.66, p &lt; 0.0001) and Native American (OR: 1.39, 95% CI: 1.34-1.44, p &lt; 0.0001) race, as well as lower income quartile (OR: 1.24, 95% CI: 1.19-1.28, p &lt; 0.001) were associated with increased odds of death during admission. Conclusions: This is the largest observational study to date to identify the impact of race and SES on pediatric cancer hospitalization and mortality in the United States. Non-white race and lower SES was associated with significantly increased odds of death during admission. Given the significant difference in mortality by race, healthcare policy makers and insurance companies should investigate the specific drivers of increased admission and mortality and develop strategies to address inequity in cancer care.

Identification of an immune signature to predict poor clinical outcome in cervical cancer.

Aim: To explore tumor immune microenvironment and identify immune prognostic-related circRNAs in cervical cancer. Materials & methods: RNA-seq in combination with bioinformatics were performed to establish a prognostic risk model and a circRNAs-miRNAs-CXCL8 network. Results: High-risk group correlated with poor survival outcome, and had lower PD-1 immunogenicity. Additionally, CXCL8 could distinguish normal tissue, low- and high-risk tumor tissues, the expression of which showed an increasing trend among the three groups. RNA-seq and bioinformatics indicated that circRNAs like hsa_circ_0025721 might upregulate CXCL8 through sponging miRNAs including hsa-miR-4428. Conclusion: We constructed an immune risk model related with CD8 T cells to predict the cervical cancer patients' prognosis and explored the abnormal expression mechanism of CXCL8 through the ceRNA mechanism.

Methylated markers accurately distinguish primary central nervous system lymphomas (PCNSL) from other CNS tumors

BackgroundDefinitive diagnosis of primary central nervous system lymphoma (PCNSL) requires invasive surgical brain biopsy, causing treatment delays. In this paper, we identified and validated tumor-specific markers that can distinguish PCNSL from other CNS tumors in tissues. In a pilot study, we tested these newly identified markers in plasma.ResultsThe Methylation Outlier Detector program was used to identify markers in TCGA dataset of 48 diffuse large B-cell lymphoma (DLBCL) and 656 glioblastomas and lower-grade gliomas. Eight methylated markers clearly distinguished DLBCL from gliomas. Marker performance was verified (ROC-AUC of ≥ 0.989) in samples from several GEO datasets (95 PCNSL; 2112 other primary CNS tumors of 11 types). Next, we developed a novel, efficient assay called Tailed Amplicon Multiplexed-Methylation-Specific PCR (TAM-MSP), which uses two of the methylation markers, cg0504 and SCG3 triplexed with ACTB. FFPE tissue sections (25 cases each) of PCNSL and eight types of other primary CNS tumors were analyzed using TAM-MSP. TAM-MSP distinguished PCNSL from the other primary CNS tumors with 100% accuracy (AUC = 1.00, 95% CI 0.95–1.00, P < 0.001). The TAM-MSP assay also detected as few as 5 copies of fully methylated plasma DNA spiked into 0.5 ml of healthy plasma. In a pilot study of plasma from 15 PCNSL, 5 other CNS tumors and 6 healthy individuals, methylation in cg0504 and SCG3 was detectable in 3/15 PCNSL samples (20%).ConclusionThe Methylation Outlier Detector program identified methylated markers that distinguish PCNSL from other CNS tumors with accuracy. The high level of accuracy achieved by these markers was validated in tissues by a novel method, TAM-MSP. These studies lay a strong foundation for a liquid biopsy-based test to detect PCNSL-specific circulating tumor DNA.

Roughness and dynamics of proliferating cell fronts as a probe of cell\u2013cell interactions

Juxtacellular interactions play an essential but still not fully understood role in both normal tissue development and tumour invasion. Using proliferating cell fronts as a model system, we explore the effects of cell–cell interactions on the geometry and dynamics of these one-dimensional biological interfaces. We observe two distinct scaling regimes of the steady state roughness of in-vitro propagating Rat1 fibroblast cell fronts, suggesting different hierarchies of interactions at sub-cell lengthscales and at a lengthscale of 2–10 cells. Pharmacological modulation significantly affects the proliferation speed of the cell fronts, and those modulators that promote cell mobility or division also lead to the most rapid evolution of cell front roughness. By comparing our experimental observations to numerical simulations of elastic cell fronts with purely short-range interactions, we demonstrate that the interactions at few-cell lengthscales play a key role. Our methodology provides a simple framework to measure and characterise the biological effects of such interactions, and could be useful in tumour phenotyping.