Clinical prognostic factors for pediatric extra-abdominal desmoid tumor: analyses of 66 patients at a single institution

Background and purpose

Pediatric desmoid tumor (PDT) is rare and has a high local recurrence rate. The purpose of the present study was to analyze clinical risk factors of local recurrence in PDT patients.

Materials and methods

We reviewed clinical data of 66 PDT patients from 2004 to 2015. All patients underwent macroscopically complete resection, and some recurrent tumors were prescribed radiotherapy. Factors such as sex, age at presentation, location, and proximity to nerves or vasculature were analyzed. The local recurrence rate and recurrence-free survival were analyzed with these factors.

Results

All patients in the present study were children and had extra-abdominal tumors. The median follow-up time was 6.6?years. Thirty-six (55%) patients had local recurrence. Age, sex, tumor site, tumor size, and proximity to nerves/vasculature had a significant impact on prognosis in univariate analysis. Radiotherapy decreased the local recurrence rate. In multivariate analysis, younger age, tumor location in buttocks, larger tumor, and proximity to important nerves/vasculature were independent risk factors for poor prognosis.

Conclusions

Favorable therapeutic strategies could be selected according to the preoperative prognostic risk factors. Radiotherapy should be considered for local recurrence of PDT.

     

Phylloides tumor of the breast: a rare neoplasm,though not that innocent

Background

Cystosarcoma phylloides (CP) is an extremely rare form of breast cancer with an unpredictable clinical course. The histological characteristics of this neoplasm have not proved to offer much in the estimation of prognosis of these patients.

Patients and methods

In our clinics, in a time period of 38 years, 22 patients with cystosarcoma phylloides were treated. There were 5 cases of malignancy, 15 cases with benign tumors, and two cases histologically characterized as borderline neoplasia. Metastases were manifested in one patient. All patients were on a 5-year follow-up, except in five cases, one operated three years ago and four operated within the last two years.

Results

16 of 22 patients did not present any signs of local recurrence or metastases. There were three patients that manifested local recurrence and underwent supplementary ongectomy or mastectomy and are free of recurrence ever since. One patient with metastatic CP died.

Conclusion

Independently of its histopathological behavior, CP is a tumor difficult to be treated. Meticulous follow-up is mandatory in order to manage possible recurrence of the neoplasm.

     

Prognostic significance of microvascular invasion in tumor stage for hepatocellular carcinoma

Background

The presence of microvascular invasion (McVI) in hepatocellular carcinoma (HCC) has been proposed as a cause of recurrence and poor survival, although this has not been officially emphasized in staging systems. Thus, we conducted a retrospective study to investigate the prognostic importance of McVI in tumor staging in patients with HCC who underwent hepatic resection.

Methods

A retrospective analysis was performed of patients who underwent hepatic resection for HCC at our center from 1994 to 2012. Patients with HCC were classified into four groups based on the presence of McVI and extent of gross vascular invasion (VI).

Results

The 5-year overall and recurrence-free survival rates of 676 patients were 63.3 and 42.6%, respectively. There was no difference in tumor recurrence or survival rate between patients with HCC and McVI without gross VI and those with gross VI confined to segmental/sectional branches. Multivariate analysis revealed that the extent of VI based on the presence of McVI and gross VI was independently associated with tumor recurrence and overall survival.

Conclusions

McVI was revealed to be an important risk factor similar to gross VI confined to a segmental/sectional branch in patients with HCC who underwent hepatic resection. This finding should be considered when estimating the stage for prognosis.

     

Estrogen Receptor-α Correlates with Higher Fungal Cell Number in Oral Paracoccidioidomycosis in Women

Background

Paracoccidioidomycosis is a neglected tropical fungal infection with great predilection for adult men, indicating the participation of female hormone estrogen in preventing paracoccidioidomycosis development in women. Estrogen has an immunologic effect leading to polarization toward the Th2 immune response, which favors the disease evolution.

Objectives

To evaluate estrogen and progesterone receptors in oral paracoccidioidomycosis lesions and to verify any association with tissue fungi counting in women and men.

Methods

Thirty-two cases of chronic oral paracoccidioidomycosis were included. Immunohistochemical analyses for anti-estrogen receptor-α, anti-progesterone receptor and anti-Paracoccidioides brasiliensis antibodies were performed. The differences between women and men and the relations among the immunomarkers for each gender were also evaluated.

Results

A significant positive correlation was observed between estrogen receptor-α and the amount of fungi in women. In addition, estrogen receptor-α was mildly expressed in the inflammatory cells of female patients, while progesterone receptor was expressed in both genders, with similar expression between women and men. Moreover, fungi counting revealed no differences between genders.

Conclusions

Estrogen receptor-α was expressed only in women and showed a positive correlation with the amount of fungi in oral paracoccidioidomycosis, while progesterone receptor was observed in both genders and exhibited no correlation with estrogen receptor-α or fungi counting.

     

Metastatic tumor cells – genotypes and phenotypes

Background

Metastasis is the primary cause of mortality in cancer patients. Therefore, elucidating the genetics and epigenetics of metastatic tumor cells and the mechanisms by which tumor cells acquire metastatic properties constitute significant challenges in cancer research.

Objective

To summarize the current understandings of the specific genotype and phenotype of the metastatic tumor cells.

Method and Result

In-depth genetic analysis of tumor cells, especially with advances in the next-generation sequencing, have revealed insights of the genotypes of metastatic tumor cells. Also, studies have shown that the cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) phenotypes are associated with the metastatic cascade.

Conclusion

In this review, we will discuss recent advances in the field by focusing on the genomic instability and phenotypic dynamics of metastatic tumor cells.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

A novel protein derived from lamprey supraneural body tissue with efficient cytocidal actions against tumor cells

Background

In previous research, we found that cell secretion from the adult lamprey supraneural body tissues possesses cytocidal activity against tumor cells, but the protein with cytocidal activity was unidentified.

Methods

A novel lamprey immune protein (LIP) as defense molecule was first purified and identified in jawless vertebrates (cyclostomes) using hydroxyapatite column and Q Sepharose Fast Flow column. After LIP stimulation, morphological changes of tumor cells were analysed and measured whether in vivo or in vitro.

Results

LIP induces remarkable morphological changes in tumor cells, including cell blebbing, cytoskeletal alterations, mitochondrial fragmentation and endoplasmic reticulum vacuolation, and most of the cytoplasmic and organelle proteins are released following treatment with LIP. LIP evokes an elevation of intracellular calcium and inflammatory molecule levels. Our analysis of the cytotoxic mechanism suggests that LIP can upregulate the expression of caspase 1, RIPK1, RIP3 to trigger pyroptosis and necroptosis. To examine the effect of LIP in vivo, tumor xenograft experiments were performed, and the results indicated that LIP inhibits tumor growth without damage to mice. In addition, the cytotoxic action of LIP depended on the phosphatidylserine (PS) content of the cell membrane.

Conclusions

These observations suggest that LIP plays a crucial role in tumor cell survival and growth. The findings will also help to elucidate the mechanisms of host defense in lamprey.

     

The involvement of osmolarity in the safety of contrast media

Background

New non-ionic contrast agents, classified into low osmolar agents and iso-osmolar agents, present different biochemical characteristics that may influence the allergic reactions they cause. The aim of our study was to evaluate how osmolarity may affect safety in the use of contrast agents.

Case presentation

Six patients with a positive history for reaction to contrast agent were included in this study. Only one patient prick and intradermal skin test was positive. However, in 5 cases, patients presented an immediate reaction after administration of contrast agent that was not IgE mediated.

Conclusions

In this study, we focused on iodixanol, an iso-osmolar contrast agent, finding good safety of this product in patients with previous hypersensitivity reactions to contrast agent.

     

Predicting ovarian cancer recurrence by plasma metabolic profiles before and after surgery

Background

Previous metabolomic studies have revealed that plasma metabolic signatures may predict epithelial ovarian cancer (EOC) recurrence. However, few studies have performed metabolic profiling of pre- and post-operative specimens to investigate EOC prognostic biomarkers.

Objective

The aims of our study were to compare the predictive performance of pre- and post-operative specimens and to create a better model for recurrence by combining biomarkers from both metabolic signatures.

Methods

Thirty-five paired plasma samples were collected from 35 EOC patients before and after surgery. The patients were followed-up until December, 2016 to obtain recurrence information. Metabolomics using rapid resolution liquid chromatography–mass spectrometry was performed to identify metabolic signatures related to EOC recurrence. The support vector machine model was employed to predict EOC recurrence using identified biomarkers.

Results

Global metabolomic profiles distinguished recurrent from non-recurrent EOC using both pre- and post-operative plasma. Ten common significant biomarkers, hydroxyphenyllactic acid, uric acid, creatinine, lysine, 3-(3,5-diiodo-4-hydroxyphenyl) lactate, phosphohydroxypyruvic acid, carnitine, coproporphyrinogen, l-beta-aspartyl-l-glutamic acid and 24,25-hydroxyvitamin D3, were identified as predictive biomarkers for EOC recurrence. The area under the receiver operating characteristic (AUC) values in pre- and post-operative plasma were 0.815 and 0.909, respectively; the AUC value after combining the two sets reached 0.964.

Conclusion

Plasma metabolomic analysis could be used to predict EOC recurrence. While post-operative biomarkers have a predictive advantage over pre-operative biomarkers, combining pre- and post-operative biomarkers showed the best predictive performance and has great potential for predicting recurrent EOC.

     

A novel bispecific antibody fusion protein co-targeting EGFR and CD47 with enhanced therapeutic index

Objective

To promote targeting specificity of anti-CD47 agents, we have constructed a novel bispecific antibody fusion protein against EGFR and CD47, which may minimize the “off-target” effects caused by CD47 expression on red blood cells.

Results

The novel bispecific antibody fusion protein, denoted as Bi-SP could simultaneously bind to EGFR and CD47 and exhibited potent phagocytosis-stimulation effects in vitro. Bi-SP treatment with a low dose more effectively inhibited tumor growth than either EGFR-targeting antibody, Pan or the SIRPα variant-Fc (SIRPαV-Fc) in the A431 xenograft tumor model. In addition, the treatment with Bi-SP produced less red blood cell (RBC) losses than the SIRPαV-Fc treatment, suggesting its potential use for minimizing RBC toxicity in therapy.

Conclusions

Bi-SP with improved therapeutic index has the potential to treat CD47+ and EGFR+ cancers in clinics.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

Algicidal effect of hybrid peptides as potential inhibitors of harmful algal blooms

Objectives

To biochemically characterize synthetic peptides to control harmful algal blooms (HABs) that cause red tides in marine water ecosystems.

Results

We present an analysis of several short synthetic peptides and their efficacy as algicidal agents. By altering the amino acid composition of the peptides we addressed the mode of algicidal action and determine the optimal balance of cationic and hydrophobic content for killing. In a controlled setting, these synthetic peptides disrupted both plasma and chloroplast membranes of several species known to result in HABs. This disruption was a direct result of the hydrophobic and cationic content of the peptide. Furthermore, by using an anti-HAB bioassay in scallops, we determined that these peptides were algicidal without being cytotoxic to other marine organisms.

Conclusions

These synthetic peptides may prove promising for general marine ecosystem remediation where HABs have become widespread and resulted in serious economic loss.

     

PTEN at the interface of immune tolerance and tumor suppression

Background

PTEN is well known to function as a tumor suppressor that antagonizes oncogenic signaling and maintains genomic stability. The PTEN gene is frequently deleted or mutated in human cancers and the wide cancer spectrum associated with PTEN deficiency has been recapitulated in a variety of mouse models of Pten deletion or mutation. Pten mutations are highly penetrant in causing various types of spontaneous tumors that often exhibit resistance to anticancer therapies including immunotherapy. Recent studies demonstrate that PTEN also regulates immune functionality.

Objective

To understand the multifaceted functions of PTEN as both a tumor suppressor and an immune regulator.

Methods

This review will summarize the emerging knowledge of PTEN function in cancer immunoediting. In addition, the mechanisms underlying functional integration of various PTEN pathways in regulating cancer evolution and tumor immunity will be highlighted.

Results

Recent preclinical and clinical studies revealed the essential role of PTEN in maintaining immune homeostasis, which significantly expands the repertoire of PTEN functions. Mechanistically, aberrant PTEN signaling alters the interplay between the immune system and tumors, leading to immunosuppression and tumor escape.

Conclusion

Rational design of personalized anti-cancer treatment requires mechanistic understanding of diverse PTEN signaling pathways in modulation of the crosstalk between tumor and immune cells.

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

     

Male breast cancer: thirteen years experience of a single center

Background

This retrospective study analysed the epidemiological, clinical, and therapeutic profiles of breast cancer in males.

Methods

We report our experience at the Hospital of the University of Baskent, where 20 cases of male breast cancer were observed and treated between 1995–2008.

Results

Median age at presentation was 66,7 ± 10,9 years. Average follow-up was 63 ± 18,5 months. The main presenting symptom was a mass in 65% of cases (13 patients). Ýnvasive ductal carcinoma was the most frequent pathologic type (70% of cases).

Conclusion

Male breast cancer patients have an incidence of prostate cancer higher than would be predicted in the general population. Cause of men have a higher rate of ER positivity the responses with hormonal agents are good.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

Renal cell -like carcinoma of the nasal cavity: a case report and review of the literature

Background

Sinonasal renal cell-like carcinoma (SRCLC) is an extremely rare low malignant tumor arising in the sinonasal tract, with histological mimicry of renal cell carcinoma.

Case presentation

We present a case of sinonasal renal cell-like carcinoma in a 63-year-old male patient. Computer tomography(CT) scanning revealed a soft tissue mass at the left nasal cavity and choana. Histologically, the predominant tumor architecture was follicular to glandular with intervening fibrous septa. The tumor cells were uniform cuboidal to polyhedral with abundant clear or eosinophilic cytoplasm. Immunohistochemically, the tumor cells were strongly positive for CK7, EMA, vimentin, SOX10, S-100, and focally positive for CA9. During 6 months of follow-up, there was no clinical or radiological evidence of recurrence or metastasis.

Conclusion

SRCLC has microscopic features which overlap with tumors that contain clear cells. Thus, several other tumors must be considered in the differential diagnosis of a tumor of the sinonasal region with clear cells, especially metastatic renal clear cell carcinoma. SRCLC is an indolent tumor and none of the reported SRCLC patients had metastatic disease.

     

Untargeted and stable isotope-assisted metabolomic analysis of MDA-MB-231 cells under hypoxia

Introduction

Hypoxia commonly occurs in cancers and is highly related with the occurrence, development and metastasis of cancer. Treatment of triple negative breast cancer remains challenge. Knowledge about the metabolic status of triple negative breast cancer cell lines in hypoxia is valuable for the understanding of molecular mechanisms of this tumor subtype to develop effective therapeutics.

Objectives

Comprehensively characterize the metabolic profiles of triple negative breast cancer cell line MDA-MB-231 in normoxia and hypoxia and the pathways involved in metabolic changes in hypoxia.

Methods

Differences in metabolic profiles affected pathways of MDA-MB-231 cells in normoxia and hypoxia were characterized using GC–MS based untargeted and stable isotope assisted metabolomic techniques.

Results

Thirty-three metabolites were significantly changed in hypoxia and nine pathways were involved. Hypoxia increased glycolysis, inhibited TCA cycle, pentose phosphate pathway and pyruvate carboxylation, while increased glutaminolysis in MDA-MB-231 cells.

Conclusion

The current results provide metabolic differences of MDA-MB-231 cells in normoxia and hypoxia conditions as well as the involved metabolic pathways, demonstrating the power of combined use of untargeted and stable isotope-assisted metabolomic methods in comprehensive metabolomic analysis.