Possible de novo clear cell carcinoma in the contralateral ovary 9 years after fertility-sparing surgery for Stage IA clear cell ovarian carcinoma

Abstract

A patient who underwent fertility-sparing surgery for Stage IA clear cell carcinoma may have developed de novo clear cell carcinoma in the contralateral ovary 9 years later. She underwent fertility-sparing surgery and postoperative adjuvant chemotherapy for right ovarian carcinoma at 33 years of age (when endometriosis was observed in the contralateral ovary). At the age of 41 years, a tumor was discovered in the left ovary. This was diagnosed pathologically as clear cell carcinoma with clear cell adenofibroma, which may have developed de novo. A consensus is currently taking shape that although fertility-sparing surgery is a therapeutic option for patients with Stage IA clear cell carcinoma, long-term outpatient monitoring is advised to watch for its recurrence or de novo development in the contralateral ovary.

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Possible de novo clear cell carcinoma in the contralateral ovary 9 years after fertility-sparing surgery for Stage IA clear cell ovarian carcinoma

Abstract

A patient who underwent fertility-sparing surgery for Stage IA clear cell carcinoma may have developed de novo clear cell carcinoma in the contralateral ovary 9 years later. She underwent fertility-sparing surgery and postoperative adjuvant chemotherapy for right ovarian carcinoma at 33 years of age (when endometriosis was observed in the contralateral ovary). At the age of 41 years, a tumor was discovered in the left ovary. This was diagnosed pathologically as clear cell carcinoma with clear cell adenofibroma, which may have developed de novo. A consensus is currently taking shape that although fertility-sparing surgery is a therapeutic option for patients with Stage IA clear cell carcinoma, long-term outpatient monitoring is advised to watch for its recurrence or de novo development in the contralateral ovary.

http://ift.tt/2g1RsZl

HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability

The integration of human papilloma virus (HPV) into host genome is one of the critical steps that lead to the progression of precancerous lesion into cancer. However, the mechanisms and consequences of such in...

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Hyaluronan synthase 2 expressed by cancer-associated fibroblasts promotes oral cancer invasion

Hyaluronan synthases (HAS) control the biosynthesis of hyaluronan (HA) and critically modulate the tumor microenviroment. Cancer-associated fibroblasts (CAFs) affect the progression of a tumor by remolding the...

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Use of poly ADP-ribose polymerase [PARP] inhibitors in cancer cells bearing DDR defects: the rationale for their inclusion in the clinic

DNA damage response (DDR) defects imply genomic instability and favor tumor progression but make the cells vulnerable to the pharmacological inhibition of the DNA repairing enzymes. Targeting cellular proteins...

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Is minimal residual disease a convincing tool to determine the treatment duration of immune checkpoint inhibitors?

Future Oncology Ahead of Print.


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Video-assisted thoracic surgery techniques for lung cancer: which is better?

Future Oncology December 2016, Vol. 12, No. 23s, Pages 1-4.


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Is minimal residual disease a convincing tool to determine the treatment duration of immune checkpoint inhibitors?

Future Oncology Ahead of Print.


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Video-assisted thoracic surgery techniques for lung cancer: which is better?

Future Oncology December 2016, Vol. 12, No. 23s, Pages 1-4.


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Cancer-related fatigue in post-treatment cancer survivors: application of the common sense model of illness representations

Abstract

Background

Cancer-related fatigue (CrF) is a common and disruptive symptom that may be experienced during and after cancer. Research into the subjective experience of fatigue in this group is required. The common sense model of self-regulation of health and illness (SRM) addresses personal beliefs or mental representations—whether medically sound or unsubstantiated— that a person holds about a health issue. The current study assesses if the SRM could be used as a theoretical framework for organizing the experiences of people with CrF, with a view to identifying methods to address fatigue in cancer survivors.

Method

Four focus groups were held with a total of 18 cancer survivors who reported they experienced 'significant fatigue or reduced energy.' A thematic analysis was conducted within the framework of the SRM.

Results

Findings were aligned with the SRM, with participants discussing fatigue with reference to representation, coping, and appraisal of symptoms. In particular, the wider social context of CrF was frequently addressed. Perceived inadequacies in support available to those with lingering fatigue after the completion of cancer treatment were highlighted by the participants.

Conclusion

This study explored the subjective experience of fatigue after cancer using the SRM. CrF should be approached as a complex psychosocial issue and considered from the patient perspective to facilitate better understanding and management of symptoms. The SRM is an applicable framework for identifying modifiable factors that could lead to improved coping with CrF in post-treatment cancer survivors.

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Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE trial

Abstract

Background

Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds. Preclinical studies in models have shown that vorinostat is able to down regulate Epidermal Growth Factor Receptor (EGFR) expression and to revert epithelial to mesenchimal transition (EMT). Due to its histone deacetylase (HDAC) inhibiting activity and its safe use as a chronic therapy for epileptic disorders, valproic acid (VPA) has been considered a good candidate for anticancer therapy. A reasonable option may be to employ the combination of cisplatin, cetuximab and VPA in recurrent/metastatic SCCHN taking advantage of the possible positive interaction between histone deacetylase inhibitors, cisplatin and/or anti-EGFR.

Method/Design

V-CHANCE is a phase 2 clinical trial evaluating, in patients with recurrent/metastatic squamous cell carcinoma of the head and neck never treated with first-line chemotherapy, the concomitant standard administration of cisplatin (on day 1, every 3 weeks) and cetuximab (on day 1, weekly), in combination with oral VPA given daily from day −14 with a titration strategy in each patient (target serum level of 50–100 μg/ml). Primary end point is the objective response rate measured according to Response Evaluation Criteria in Solid Tumors (RECIST). Sample size, calculated according to Simon 2 stage minimax design will include 21 patients in the first stage with upper limit for rejection being 8 responses, and 39 patients in the second stage, with upper limit for rejection being 18 responses. Secondary endpoints are time to progression, duration of response, overall survival, safety.

Objectives of the translational study are the evaluation on tumor samples of markers of treatment efficacy/resistance (i.e. γH2AX, p21/WAF, RAD51, XRCC1, EGFR, p-EGFR, Ki-67) and specific markers of VPA HDAC inhibitory activity (histones and proteins acetylation, Histone deacetylase isoforms) as well as valproate test, histones and proteins acetylation of peripheral blood mononuclear cell, tested on blood samples at baseline and at different time points during treatment.

Discussion

Overall, this study could provide a less toxic and more effective first-line chemotherapy regimen in patients with recurrent/metastatic squamous cell carcinoma of the head and neck by demonstrating the feasibility and efficacy of cisplatin/cetuximab plus valproic acid. Moreover, correlative studies could help to identify responder patients, and will add insights in the mechanism of the synergistic interaction between these agents.

EudraCT Number

2014-001523-69

Trial registration

ClinicalTrials.gov number, NCT02624128

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Anti-LRP/LR-specific antibody IgG1-iS18 impedes adhesion and invasion of pancreatic cancer and neuroblastoma cells

Abstract

Background

Cancer has become a global burden due to its high incidence and mortality rates, with an estimated 14.1 million cancer cases reported worldwide in 2012 particularly as a result of metastasis. Metastasis involves two crucial steps: adhesion and invasion, and the non-integrin receptor; the 37-kDa/67-kDa laminin receptor precursor/ high affinity laminin receptor (LRP/LR) has been shown to be overexpressed on the surface of tumorigenic cells, thus being implicated in the enhancement of these two crucial steps. The current study investigated the role of LRP/LR on the aggressiveness of pancreatic cancer (AsPC-1) and neuroblastoma (IMR-32) cells with respect to their adhesive and invasive potential.

Methods

AsPC-1 and IMR-32 cells were utilized as the experimental cell lines for the study. Cell surface LRP/LR levels were visualised and quantified on the experimental and control (MCF-7) cell lines via confocal microscopy and flow cytometry, respectively. Total LRP/LR levels in the cell lines were assessed by Western blotting and the adhesive and invasive potential of the above-mentioned cell lines was determined before and after supplementation with the anti-LRP/LR specific antibody IgG1-iS18. Statistical significance of the data was confirmed via the use of the two-tailed student's t-test and Pearson's correlation coefficient.

Results

Flow cytometry revealed that AsPC-1 and IMR-32 cells displayed significantly higher cell surface LRP/LR levels in comparison to the MCF-7 control cell line. However, Western blotting and subsequent densitometric analysis revealed that all three tumorigenic cell lines displayed no significant difference in total LRP/LR levels. The treatment of AsPC-1 and IMR-32 cells with IgG1-iS18 caused a significant reduction in the adhesive and invasive potential of the cells to laminin-1 and through the ECM-like Matrigel™, respectively. Pearson's correlation coefficients indicated a high correlation, thus suggesting a directly proportional relationship between cell surface LRP/LR levels and the adhesive and invasive potential of AsPC-1 and IMR-32 cells.

Conclusion

These findings suggest that through the interference of the LRP/LR-laminin-1 interaction, the anti-LRP/LR specific antibody IgG1-iS18 may act as an alternative therapeutic tool for the treatment of metastatic pancreatic cancer and neuroblastoma.

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Cancer-related fatigue in post-treatment cancer survivors: application of the common sense model of illness representations

Abstract

Background

Cancer-related fatigue (CrF) is a common and disruptive symptom that may be experienced during and after cancer. Research into the subjective experience of fatigue in this group is required. The common sense model of self-regulation of health and illness (SRM) addresses personal beliefs or mental representations—whether medically sound or unsubstantiated— that a person holds about a health issue. The current study assesses if the SRM could be used as a theoretical framework for organizing the experiences of people with CrF, with a view to identifying methods to address fatigue in cancer survivors.

Method

Four focus groups were held with a total of 18 cancer survivors who reported they experienced 'significant fatigue or reduced energy.' A thematic analysis was conducted within the framework of the SRM.

Results

Findings were aligned with the SRM, with participants discussing fatigue with reference to representation, coping, and appraisal of symptoms. In particular, the wider social context of CrF was frequently addressed. Perceived inadequacies in support available to those with lingering fatigue after the completion of cancer treatment were highlighted by the participants.

Conclusion

This study explored the subjective experience of fatigue after cancer using the SRM. CrF should be approached as a complex psychosocial issue and considered from the patient perspective to facilitate better understanding and management of symptoms. The SRM is an applicable framework for identifying modifiable factors that could lead to improved coping with CrF in post-treatment cancer survivors.

http://ift.tt/2fOi5hp

Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE trial

Abstract

Background

Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds. Preclinical studies in models have shown that vorinostat is able to down regulate Epidermal Growth Factor Receptor (EGFR) expression and to revert epithelial to mesenchimal transition (EMT). Due to its histone deacetylase (HDAC) inhibiting activity and its safe use as a chronic therapy for epileptic disorders, valproic acid (VPA) has been considered a good candidate for anticancer therapy. A reasonable option may be to employ the combination of cisplatin, cetuximab and VPA in recurrent/metastatic SCCHN taking advantage of the possible positive interaction between histone deacetylase inhibitors, cisplatin and/or anti-EGFR.

Method/Design

V-CHANCE is a phase 2 clinical trial evaluating, in patients with recurrent/metastatic squamous cell carcinoma of the head and neck never treated with first-line chemotherapy, the concomitant standard administration of cisplatin (on day 1, every 3 weeks) and cetuximab (on day 1, weekly), in combination with oral VPA given daily from day −14 with a titration strategy in each patient (target serum level of 50–100 μg/ml). Primary end point is the objective response rate measured according to Response Evaluation Criteria in Solid Tumors (RECIST). Sample size, calculated according to Simon 2 stage minimax design will include 21 patients in the first stage with upper limit for rejection being 8 responses, and 39 patients in the second stage, with upper limit for rejection being 18 responses. Secondary endpoints are time to progression, duration of response, overall survival, safety.

Objectives of the translational study are the evaluation on tumor samples of markers of treatment efficacy/resistance (i.e. γH2AX, p21/WAF, RAD51, XRCC1, EGFR, p-EGFR, Ki-67) and specific markers of VPA HDAC inhibitory activity (histones and proteins acetylation, Histone deacetylase isoforms) as well as valproate test, histones and proteins acetylation of peripheral blood mononuclear cell, tested on blood samples at baseline and at different time points during treatment.

Discussion

Overall, this study could provide a less toxic and more effective first-line chemotherapy regimen in patients with recurrent/metastatic squamous cell carcinoma of the head and neck by demonstrating the feasibility and efficacy of cisplatin/cetuximab plus valproic acid. Moreover, correlative studies could help to identify responder patients, and will add insights in the mechanism of the synergistic interaction between these agents.

EudraCT Number

2014-001523-69

Trial registration

ClinicalTrials.gov number, NCT02624128

http://ift.tt/2g1vUvI

Anti-LRP/LR-specific antibody IgG1-iS18 impedes adhesion and invasion of pancreatic cancer and neuroblastoma cells

Abstract

Background

Cancer has become a global burden due to its high incidence and mortality rates, with an estimated 14.1 million cancer cases reported worldwide in 2012 particularly as a result of metastasis. Metastasis involves two crucial steps: adhesion and invasion, and the non-integrin receptor; the 37-kDa/67-kDa laminin receptor precursor/ high affinity laminin receptor (LRP/LR) has been shown to be overexpressed on the surface of tumorigenic cells, thus being implicated in the enhancement of these two crucial steps. The current study investigated the role of LRP/LR on the aggressiveness of pancreatic cancer (AsPC-1) and neuroblastoma (IMR-32) cells with respect to their adhesive and invasive potential.

Methods

AsPC-1 and IMR-32 cells were utilized as the experimental cell lines for the study. Cell surface LRP/LR levels were visualised and quantified on the experimental and control (MCF-7) cell lines via confocal microscopy and flow cytometry, respectively. Total LRP/LR levels in the cell lines were assessed by Western blotting and the adhesive and invasive potential of the above-mentioned cell lines was determined before and after supplementation with the anti-LRP/LR specific antibody IgG1-iS18. Statistical significance of the data was confirmed via the use of the two-tailed student's t-test and Pearson's correlation coefficient.

Results

Flow cytometry revealed that AsPC-1 and IMR-32 cells displayed significantly higher cell surface LRP/LR levels in comparison to the MCF-7 control cell line. However, Western blotting and subsequent densitometric analysis revealed that all three tumorigenic cell lines displayed no significant difference in total LRP/LR levels. The treatment of AsPC-1 and IMR-32 cells with IgG1-iS18 caused a significant reduction in the adhesive and invasive potential of the cells to laminin-1 and through the ECM-like Matrigel™, respectively. Pearson's correlation coefficients indicated a high correlation, thus suggesting a directly proportional relationship between cell surface LRP/LR levels and the adhesive and invasive potential of AsPC-1 and IMR-32 cells.

Conclusion

These findings suggest that through the interference of the LRP/LR-laminin-1 interaction, the anti-LRP/LR specific antibody IgG1-iS18 may act as an alternative therapeutic tool for the treatment of metastatic pancreatic cancer and neuroblastoma.

http://ift.tt/2g1skBL

A consensus statement on the gender perspective in lung cancer

Abstract

Lung cancer is the most common cancer globally and has the highest mortality. Although this disease is not associated with a particular gender, its incidence is rising among women, who are diagnosed at an increasingly younger age compared with men. One of the main reasons for this rise is women taking up smoking. However, many non-smoking women also develop this disease. Other risk factors implicated in the differential development of lung cancer in women are genetic predisposition, tumour histology and molecular profile. Proportionally more women than men with lung cancer have a mutation in the EGFR gene. This consensus statement reviews the available evidence about the epidemiological, biological, diagnostic, therapeutic, social and psychological aspects of lung cancer in women.

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Injectable mineral supplementation to transition period dairy cows and its effects on animal health

Abstract

The dairy cattle production rises worldwide, with genetically selected animals. Consequently, they present high nutritional requirements, especially during the transition period. The aim of this study was to evaluate the effects of parenteral supplementation of a mineral blend composed by selenium, copper, magnesium, phosphorus, and potassium on hematological, biochemical, immunological, and antioxidant status in transition period dairy cows and newborn calves. The Holstein cows were divided into the control group (A, n = 3) and treated group (B, n = 4), which were supplemented twice with an intramuscularly dose of 10 mL/animal, at approximately 20 days prior to the parturition, and a subsequent dose at the parturition. Total blood was collected from cows on days 20 and 5 antepartum, and 2 and 7 postpartum, and from calves, at the birth. We observed a decreased in concentrations of thiobarbituric acid reactive substances (TBARSs) for cows fed mineral blend during the transition period (P < 0.05), as well as a greater number of total leukocyte, total protein and globulin levels, and reduction of hemoglobin levels (P < 0.05). The catalase activity was increased in supplemented cows and in its calves (P < 0.05). Therefore, based on these evidences, the parenteral supplementation with mineral provides beneficial effects in pregnant cows and during the transition period, as well as in their calves.

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Letter to editor: Incorrect identification of study species

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Haematology and some serum biochemistry of apparently healthy Muturu and Bunaji breeds of cattle in Benue State, Nigeria

Abstract

The haematological and serum biochemical values of 100 Muturu cattle and 100 Bunaji cattle were studied in two local government areas of Benue State, Nigeria. Haematocrit, red blood cell count, haemoglobin, total white blood cell count, lymphocyte and monocyte counts were significantly higher in Muturu cattle than the Bunaji cattle. However, there were no significant differences in the mean corpuscular volume, mean corpuscular haemoglobin, neutrophil, eosinophil, and basophil counts, albumin, urea, alanine aminotransferase and alkaline phosphatase in the two breeds of cattle. Lower values of mean corpuscular haemoglobin concentration and platelet counts were observed in the Muturu cattle. Similarly, total protein and globulin values were significantly lower in Bunaji than Muturu cattle while the converse is the case with aspartate aminotransferase. The haematological parameters of the two breeds were within the recognized reference intervals for cattle. This study reports for the first time the haematological and some biochemical parameters for Muturu cattle in Benue State.

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Assessment of impact of hemodialysis on hematological parameters among patients with chronic kidney disease

Abstract

Chronic kidney disease is a condition in which the kidney fails to function adequately. End-stage renal disease is the terminal stage of chronic renal failure where there is an irreversible progressive deterioration in renal function which can be substituted by hemodialysis (HD), peritoneal dialysis (PD), or renal transplantation. Both types of dialysis can cause side effects on the blood components. The objectives of this study was to find the changes in the complete blood counts, red blood cell indices, and peripheral blood smear in post hemodialysis patients and to compare the changes with respect to pre-dialysis status. We conducted a hospital-based cross-sectional study for a period of 3 years and a total of 120 patients undergoing dialysis. Blood samples were collected before and within 2 h post dialysis; complete hemogram and peripheral smear examination results were recorded and compared by Student t test. There was moderate degree of anemia in both pre- and post dialysis patients, and also, there was an increase in the severity of anemia after hemodialysis in many patients. The type of anemia was normocytic normochromic. There was a statistically significant decrease in total leukocyte count and platelet count (p < 0.05). Significant variations were also noted in differential count with a decrease in neutrophil along with monocyte count and an increase in lymphocyte as well as eosinophil count. The results of this study showed that many hematological parameters measured in post dialysis patients were either increased or decreased in comparison with pre-dialysis values. The present study might help clinicians to initiate precautions before and after dialysis procedures and thereby reduce anemia, thrombosis, hemorrhage, and related complications.

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Pathology of muscular steatosis in the bovine species: report of two spontaneously arising cases and comparative overview of the condition

Abstract

Muscular steatosis, a condition characterized by prominent fatty replacement of skeletal muscles, has been known from a long time ago to mainly involve meat animals, such as pig, sheep, and cattle. Although a variety of hypotheses are proposed for explaining the condition, its etiology and pathogenesis are still poorly understood. Spontaneously occurring lesions of muscular steatosis were recognized in two 2-year-old steers that were slaughtered for food. Significant clinical abnormalities indicative of motor dysfunction were not observed in these animals. Postmortem examination revealed a remarkable and bilaterally symmetrical deposition of adipose tissue in the semitendinosus muscle of one steer and the gluteus muscle of the other steer. Affected muscles were of normal volume but exhibited an irregularly streaked appearance due to ill-proportioned fat infiltration. On histopathology, the lesioned muscles were extensively replaced by much adipose tissue, showing complete loss of muscle fibers in some fascicles. Structure of the perimysial connective tissue network was well preserved. All fat cells did not exhibit immature morphology but were of a well-differentiated mature appearance. Although a small number of muscle fibers represented atrophic or degenerative changes, regenerative muscle fibers and proliferation of the perimysial connective tissue were not demonstrated elsewhere in the lesions. Intramuscular blood vessels and nerves showed no significant changes. Precise pathogenesis of muscular steatosis, such as that found in these steers, remained uncertain. These fatty muscular lesions were distinguished from those of advanced or end stages in previously described muscle disorders in cattle, including neurogenic muscular atrophy, nutritional myopathy, or muscular dystrophy. The present article makes a comment on the pathology of muscular steatosis involving the bovine species from the comparative viewpoint.

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Distribution of FDG-avid nodes in esophageal cancer: implications for radiotherapy target delineation

Abstract

Purpose

Clinical target volumes (CTV) for radiotherapy (RT) in esophageal cancer (EC) are based on standard expansions of primary tumor volume. Data is needed to define regions at highest risk for occult disease, based on histology and location of the primary tumor. We therefore reviewed PET scans in EC patients to characterize the location of FDG-avid lymph node metastases (LNM).

Materials and methods

We identified 473 EC patients with reviewable pre-treatment PET-CT scans. Tumors were classified by histology and location; 85% were distal or GE junction tumors and 71% were adenocarcinoma. FDG-avid LNM were classified using standard radiographic nodal atlases, and distances from primary tumor to paraesophageal LNM were also measured.

Results

The most common LNM in upper EC were supraclavicular, retrotracheal and paratracheal. The most common LNM in lower EC were paraesophageal and in the gastrohepatic space. Overall, 55% of paraesophageal LNM were adjacent to primary tumor. Of upper esophageal tumors with paraesophageal LNM, 87% were adjacent to the tumor and none were >6 cm from tumor. However, 57% of lower esophageal tumors with paraesophageal LNM had non-adjacent paraesophageal nodes, 24% of which were >8 cm from the tumor.

Conclusion

A more data-driven and individualized approach to CTV delineation could improve the therapeutic ratio of RT in esophageal cancer. These results can guide CTV delineation by indicating the potential distribution of nodal involvement in esophageal cancer.

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Cancer somatic mutations cluster in a subset of regulatory sites predicted from the ENCODE data

Abstract

Background

Transcriptional regulation of gene expression is essential for cellular differentiation and function, and defects in the process are associated with cancer. The ENCODE project has mapped potential regulatory sites across the complete genome in many cell types, and these regions have been shown to harbour many of the somatic mutations that occur in cancer cells, suggesting that their effects may drive cancer initiation and development. The ENCODE data suggests a very large number of regulatory sites, and methods are needed to identify those that are most relevant and to connect them to the genes that they control.

Methods

Predictive models of gene expression were developed by integrating the ENCODE data for regulation, including transcription factor binding and DNase1 hypersensitivity, with RNA-seq data for gene expression. A penalized regression method was used to identify the most predictive potential regulatory sites for each transcript. Known cancer somatic mutations from the COSMIC database were mapped to potential regulatory sites, and we examined differences in the mapping frequencies associated with sites chosen in regulatory models and other (rejected) sites. The effects of potential confounders, for example replication timing, were considered.

Results

Cancer somatic mutations preferentially occupy those regulatory regions chosen in our models as most predictive of gene expression.

Conclusion

Our methods have identified a significantly reduced set of regulatory sites that are enriched in cancer somatic mutations and are more predictive of gene expression. This has significance for the mechanistic interpretation of cancer mutations, and the understanding of genetic regulation.

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Cancer somatic mutations cluster in a subset of regulatory sites predicted from the ENCODE data

Abstract

Background

Transcriptional regulation of gene expression is essential for cellular differentiation and function, and defects in the process are associated with cancer. The ENCODE project has mapped potential regulatory sites across the complete genome in many cell types, and these regions have been shown to harbour many of the somatic mutations that occur in cancer cells, suggesting that their effects may drive cancer initiation and development. The ENCODE data suggests a very large number of regulatory sites, and methods are needed to identify those that are most relevant and to connect them to the genes that they control.

Methods

Predictive models of gene expression were developed by integrating the ENCODE data for regulation, including transcription factor binding and DNase1 hypersensitivity, with RNA-seq data for gene expression. A penalized regression method was used to identify the most predictive potential regulatory sites for each transcript. Known cancer somatic mutations from the COSMIC database were mapped to potential regulatory sites, and we examined differences in the mapping frequencies associated with sites chosen in regulatory models and other (rejected) sites. The effects of potential confounders, for example replication timing, were considered.

Results

Cancer somatic mutations preferentially occupy those regulatory regions chosen in our models as most predictive of gene expression.

Conclusion

Our methods have identified a significantly reduced set of regulatory sites that are enriched in cancer somatic mutations and are more predictive of gene expression. This has significance for the mechanistic interpretation of cancer mutations, and the understanding of genetic regulation.

http://ift.tt/2gejM8m

Products based on olive oil, betaine, and xylitol in the post-radiotherapy xerostomia

Publication date: January–February 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 1
Author(s): Margarita Martín, Alicia Marín, Mario López, Olga Liñán, Felipe Alvarenga, David Büchser, Laura Cerezo
AimThe objective of this study was determining if the use of products based in olive oil, betaine and xylitol are efficacious to decrease the impact of the dry mouth in the quality of life of the patients with xerostomia due to radiotherapy treatment.BackgroundFollowing therapeutic irradiation of the head and neck, patients with profound xerostomia have complaints associated with oral dryness, speech, and taste. There is no strong evidence that any topical therapy is effective for relieving the symptom of dry mouth.Material and methods40 patients who had been treated with radiotherapy for head and neck carcinoma and reported symptoms of dry mouth were included in the study. A xerostomia-related quality of life questionnaire, visual analogue scale questionnaire for subjective assessment of salivary dysfunction and salivary flow were reported before and 15 days after the use of topical products based on olive oil, betaina and xylitol.ResultsThe four primary quality of life areas demonstrated significantly greater improvement after the use of topical products and all eight VAS items had favourable changes. The reduction of symptoms was statistically significant in 7 of the 8 items. After the use of the products, there were improvements in salivary flow in 45%.ConclusionsThe use of products based on olive oil, betaine and xylitol, shaped like collutory, toothpaste, gel and spray significantly improved most symptoms and the quality of life limitations produced by dry mouth in patients treated with radiotherapy.



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Long term clinical toxicity of radiation therapy in prostate cancer patients with Inflammatory Bowel Disease

Publication date: January–February 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 1
Author(s): Matthew M. Gestaut, Gregory P. Swanson
AimThe study's aim was to examine the clinical impact of radiation therapy (RT) on GI toxicity in Inflammatory Bowel Disease (IBD) patients.BackgroundIBD has long been considered a risk factor for increased bowel toxicity from RT; however, minimal evidence exists on patients with prostate cancer (PC) and IBD.Materials and methodsThe tumor registry was queried for patients with IBD and PC from the years 1990–2013. A retrospective review was conducted for patients who received RT. Radiation treatment and toxicity data were collected.ResultsAverage length of follow-up was 12 years (median 9.54, range 0.42–19.9). The majority had well controlled baseline bowel function on medical management. Prior to radiation, 60% of patients (9/15) and 40% (6/15) reported grade 0 (G0) and grade (G1) diarrhea at baseline, respectively. No baseline proctitis existed. Following radiation treatment, 78% (14/18) of patients experienced G0 diarrhea while 22% (4/18) reported G1 diarrhea. No patients suffered from greater than G1 diarrhea. Sixty-six percent (12/18), 17% (3/18) and 17% (3/18) of patients experienced G0, G1, and G2 proctitis, respectively. No patients suffered post-radiation stricture formation, and all patients with G2 proctitis received 3dCRT.ConclusionsLimited published data is available exploring RT for patients with PC and IBD. This analysis offers valuable insight into appropriate counseling for a rare patient subset. Radiation improved late G1 diarrhea rates. Grade 2 proctitis was only encountered in 3dCRT patients. No post-radiation complications occurred. Our findings suggest that IBD patients experience minimal toxicity in the era of IMRT based RT.



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Robotic radiosurgery for the treatment of liver metastases

Publication date: Available online 24 November 2016
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Rafael García, Iciar Santa-Olalla, Jose Luis Lopez Guerra, Silvia Sanchez, Ignacio Azinovic
AimThis study evaluates the toxicity and outcome in patients treated with robotic radiosurgery for liver metastases.BackgroundModern technologies allow the delivery of high doses to the liver metastases while lowering the dose to the neighboring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known yet.Methods and materialsA total of 9 patients with 17 liver metastases have been treated with robotic stereotactic body radiotherapy SBRT from March 2011 to December 2014. Local response to SBRT was graded by the Response Evaluation Criteria in Solid Tumors criteria to describe change in treated tumor lesion. Adverse events after SBRT were graded on a 1–5 scale according to the National Cancer Institute common terminology criteria for adverse events v4.0.ResultsPatients received either three (78%) or five (22%) fractions. Patients were treated with a mean fraction dose of 14Gy with a range from 9 to 20Gy. The median total radiation dose provided to patients was 45Gy with a range of 45–60Gy. Four out of the 17 (23.5%) treated lesions had a complete response, 9 (53%) partial response and 3 (17.6%) stable disease. With a median follow-up of 15.2 months after SBRT treatment, local control and overall survival rated were 89% and 66%, respectively. No patient experienced grade ≥3 toxicity. The most common toxicity reported was asthenia. Only two patients had nausea and diarrhea, 10 and 14 days after SBRT, respectively.ConclusionsRobotic radiosurgery is a safe and effective local treatment option for secondary liver tumors. Further prospective studies are ongoing to determine long-term response and survival after robotic-SBRT for liver metastases.



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Reply letter to “Texture analysis of parotid gland as a predictive factor of radiation induced xerostomia: A subset analysis”

We would like to thank Nardone and colleagues for their reply and valuable comments, and we are pleased that our findings that textural image biomarkers (IBMs), which indicate heterogeneity, significantly improved the prediction of late xerostomia [1] are confirmed by their results. Unfortunately, we can only assume that the authors also observed that more heterogeneous parotid tissue was associated with a higher risk of developing late xerostomia, as their letter does not contain information on effect sizes of the heterogeneity measures.

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Hepatic encephalopathy: present and future

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HBK-14 and HBK-15 with antidepressant-like and/or memory-enhancing properties increase serotonin levels in the hippocampus after chronic treatment in mice

Abstract

5-HT_1A and 5-HT₇ receptor ligands might have antidepressant-like properties and improve cognitive function. We previously reported significant antidepressant- and anxiolytic-like effects of two dual 5-HT_1A and 5-HT₇ receptor antagonists in various behavioral tests in rodents. As a continuation of our previous experiments, in this study we aimed to investigate whether chronic administration of 1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15) caused antidepressant-like effects and elevated serotonin levels in the murine hippocampus. We also evaluated cholinolytic properties and the influence of acute administration of both compounds on cognitive function in mice. To assess antidepressant-like properties and the influence on learning and memory we used forced swim test and step-through passive avoidance task in mice, respectively. Both compounds showed antidepressant-like properties and significantly elevated serotonin levels in the hippocampus after chronic treatment (HBK-14 – 2.5 mg/kg; HBK-15 – 0.625 and 1.25 mg/kg). HBK-15 administered chronically antidepressant-like activity at lower dose (0.625 mg/kg) than the dose active after acute treatment (1.25 mg/kg). None of the compounds affected locomotor activity of mice. HBK-15 possessed very weak cholinolytic properties, whereas HBK-14 did not show any effect on muscarinic receptors. Only HBK-15 (0.625 mg/kg) presented memory-enhancing properties and ameliorated cognitive impairments caused by scopolamine (1 mg/kg). Our results indicate that 5-HT_1A and 5-HT₇ antagonists might have potential in the treatment of depression and possess positive influence on cognitive function.

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Hepatic encephalopathy: present and future

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HBK-14 and HBK-15 with antidepressant-like and/or memory-enhancing properties increase serotonin levels in the hippocampus after chronic treatment in mice

Abstract

5-HT_1A and 5-HT₇ receptor ligands might have antidepressant-like properties and improve cognitive function. We previously reported significant antidepressant- and anxiolytic-like effects of two dual 5-HT_1A and 5-HT₇ receptor antagonists in various behavioral tests in rodents. As a continuation of our previous experiments, in this study we aimed to investigate whether chronic administration of 1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15) caused antidepressant-like effects and elevated serotonin levels in the murine hippocampus. We also evaluated cholinolytic properties and the influence of acute administration of both compounds on cognitive function in mice. To assess antidepressant-like properties and the influence on learning and memory we used forced swim test and step-through passive avoidance task in mice, respectively. Both compounds showed antidepressant-like properties and significantly elevated serotonin levels in the hippocampus after chronic treatment (HBK-14 – 2.5 mg/kg; HBK-15 – 0.625 and 1.25 mg/kg). HBK-15 administered chronically antidepressant-like activity at lower dose (0.625 mg/kg) than the dose active after acute treatment (1.25 mg/kg). None of the compounds affected locomotor activity of mice. HBK-15 possessed very weak cholinolytic properties, whereas HBK-14 did not show any effect on muscarinic receptors. Only HBK-15 (0.625 mg/kg) presented memory-enhancing properties and ameliorated cognitive impairments caused by scopolamine (1 mg/kg). Our results indicate that 5-HT_1A and 5-HT₇ antagonists might have potential in the treatment of depression and possess positive influence on cognitive function.

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A consensus statement on the gender perspective in lung cancer

Abstract

Lung cancer is the most common cancer globally and has the highest mortality. Although this disease is not associated with a particular gender, its incidence is rising among women, who are diagnosed at an increasingly younger age compared with men. One of the main reasons for this rise is women taking up smoking. However, many non-smoking women also develop this disease. Other risk factors implicated in the differential development of lung cancer in women are genetic predisposition, tumour histology and molecular profile. Proportionally more women than men with lung cancer have a mutation in the EGFR gene. This consensus statement reviews the available evidence about the epidemiological, biological, diagnostic, therapeutic, social and psychological aspects of lung cancer in women.

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Imaging findings of adrenal primitive neuroectodermal tumors: a series of seven cases

Abstract

Objective

To explore the imaging features of adrenal primitive neuroectodermal tumors (PNETs).

Materials and methods

This retrospective study included seven patients with surgically and pathologically confirmed adrenal PNETs. Among them, six underwent computed tomography (CT) scans, and one underwent magnetic resonance imaging. The imaging findings, including size, shape, margin, hemorrhage, calcification, cystic degeneration, regional lymph nodes involvement, tumor thrombus formation and enhancement pattern, were retrospectively analyzed.

Results

Among the seven adrenal PNET patients, six were male, and one was female. The median age was 26 years (range 2–56 years). The disease generally presented with either insidious symptoms (n = 4) or non-specific symptoms, including right flank pain (n = 1) and left upper abdominal discomfort (n = 2). On the pre-enhanced CT images, the tumor usually appeared as a well-defined, rounded or oval, heterogeneous mass without calcification. Certain tissue characteristics, such as cystic degeneration (n = 5), capsule (n = 4) and hemorrhage (n = 2), were observed. Regional lymph node involvement was observed in three cases, and renal vein thrombus was observed in one case. All cases showed mild heterogeneous enhancement of the tumor on the enhanced CT images.

Conclusion

An adrenal PNET commonly presents as a relatively large, well-defined, heterogeneous mass with cystic degeneration, necrosis and a characteristic mild contrast-enhancement pattern on multiphase enhanced images. PNET should be considered when the diagnosis of common tumors is not favored by signs on images.

Clinical Trial Registration Statement

This study was approved by the medical ethics committee of Xiangya Hospital, Central South University. The approval number is 201512538.

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A consensus statement on the gender perspective in lung cancer

Abstract

Lung cancer is the most common cancer globally and has the highest mortality. Although this disease is not associated with a particular gender, its incidence is rising among women, who are diagnosed at an increasingly younger age compared with men. One of the main reasons for this rise is women taking up smoking. However, many non-smoking women also develop this disease. Other risk factors implicated in the differential development of lung cancer in women are genetic predisposition, tumour histology and molecular profile. Proportionally more women than men with lung cancer have a mutation in the EGFR gene. This consensus statement reviews the available evidence about the epidemiological, biological, diagnostic, therapeutic, social and psychological aspects of lung cancer in women.

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Imaging findings of adrenal primitive neuroectodermal tumors: a series of seven cases

Abstract

Objective

To explore the imaging features of adrenal primitive neuroectodermal tumors (PNETs).

Materials and methods

This retrospective study included seven patients with surgically and pathologically confirmed adrenal PNETs. Among them, six underwent computed tomography (CT) scans, and one underwent magnetic resonance imaging. The imaging findings, including size, shape, margin, hemorrhage, calcification, cystic degeneration, regional lymph nodes involvement, tumor thrombus formation and enhancement pattern, were retrospectively analyzed.

Results

Among the seven adrenal PNET patients, six were male, and one was female. The median age was 26 years (range 2–56 years). The disease generally presented with either insidious symptoms (n = 4) or non-specific symptoms, including right flank pain (n = 1) and left upper abdominal discomfort (n = 2). On the pre-enhanced CT images, the tumor usually appeared as a well-defined, rounded or oval, heterogeneous mass without calcification. Certain tissue characteristics, such as cystic degeneration (n = 5), capsule (n = 4) and hemorrhage (n = 2), were observed. Regional lymph node involvement was observed in three cases, and renal vein thrombus was observed in one case. All cases showed mild heterogeneous enhancement of the tumor on the enhanced CT images.

Conclusion

An adrenal PNET commonly presents as a relatively large, well-defined, heterogeneous mass with cystic degeneration, necrosis and a characteristic mild contrast-enhancement pattern on multiphase enhanced images. PNET should be considered when the diagnosis of common tumors is not favored by signs on images.

Clinical Trial Registration Statement

This study was approved by the medical ethics committee of Xiangya Hospital, Central South University. The approval number is 201512538.

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Pre-clinical quantitative imaging and mouse-specific dosimetry for 111 In-labelled radiotracers

Abstract

Background

Accurate quantification in molecular imaging is essential to improve the assessment of novel drugs and compare the radiobiological effects of therapeutic agents prior to in-human studies. The aim of this study was to investigate the challenges and feasibility of pre-clinical quantitative imaging and mouse-specific dosimetry of ¹¹¹In-labelled radiotracers.

Attenuation, scatter and partial volume effects were studied using phantom experiments, and an activity calibration curve was obtained for varying sphere sizes. Six SK-OV-3-tumour bearing mice were injected with ¹¹¹In-labelled HER2-targeting monoclonal antibodies (mAbs) (range 5.58–8.52 MBq). Sequential SPECT imaging up to 197 h post-injection was performed using the Albira SPECT/PET/CT pre-clinical scanner. Mice were culled for quantitative analysis of biodistribution studies. The tumour activity, mass and percentage of injected activity per gram of tissue (%IA/g) were calculated at the final scan time point and compared to the values determined from the biodistribution data. Delivered ¹¹¹In-labelled mAbs tumour absorbed doses were calculated using mouse-specific convolution dosimetry, and absorbed doses for ⁹⁰Y-labelled mAbs were extrapolated under the assumptions of equivalent injected activities, biological half-lives and uptake distributions as for ¹¹¹In.

Results

For the sphere sizes investigated (volume 0.03–1.17 ml), the calibration factor varied by a factor of 3.7, whilst for the range of tumour masses in the mice (41–232 mg), the calibration factor changed by a factor of 2.5. Comparisons between the mice imaging and the biodistribution results showed a statistically significant correlation for the tumour activity (r = 0.999, P < 0.0001) and the tumour mass calculations (r = 0.977, P = 0.0008), whilst no correlation was found for the %IA/g (r = 0.521, P = 0.29). Median tumour-absorbed doses per injected activity of 52 cGy/MBq (range 36–69 cGy/MBq) and 649 cGy/MBq (range 441–950 cGy/MBq) were delivered by ¹¹¹In-labelled mAbs and extrapolated for ⁹⁰Y-labelled mAbs, respectively.

Conclusions

This study demonstrates the need for multidisciplinary efforts to standardise imaging and dosimetry protocols in pre-clinical imaging. Accurate image quantification can improve the calculation of the activity, %IA/g and absorbed dose. Diagnostic imaging could be used to estimate the injected activities required for therapeutic studies, potentially reducing the number of animals used.

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Pre-clinical quantitative imaging and mouse-specific dosimetry for 111 In-labelled radiotracers

Abstract

Background

Accurate quantification in molecular imaging is essential to improve the assessment of novel drugs and compare the radiobiological effects of therapeutic agents prior to in-human studies. The aim of this study was to investigate the challenges and feasibility of pre-clinical quantitative imaging and mouse-specific dosimetry of ¹¹¹In-labelled radiotracers.

Attenuation, scatter and partial volume effects were studied using phantom experiments, and an activity calibration curve was obtained for varying sphere sizes. Six SK-OV-3-tumour bearing mice were injected with ¹¹¹In-labelled HER2-targeting monoclonal antibodies (mAbs) (range 5.58–8.52 MBq). Sequential SPECT imaging up to 197 h post-injection was performed using the Albira SPECT/PET/CT pre-clinical scanner. Mice were culled for quantitative analysis of biodistribution studies. The tumour activity, mass and percentage of injected activity per gram of tissue (%IA/g) were calculated at the final scan time point and compared to the values determined from the biodistribution data. Delivered ¹¹¹In-labelled mAbs tumour absorbed doses were calculated using mouse-specific convolution dosimetry, and absorbed doses for ⁹⁰Y-labelled mAbs were extrapolated under the assumptions of equivalent injected activities, biological half-lives and uptake distributions as for ¹¹¹In.

Results

For the sphere sizes investigated (volume 0.03–1.17 ml), the calibration factor varied by a factor of 3.7, whilst for the range of tumour masses in the mice (41–232 mg), the calibration factor changed by a factor of 2.5. Comparisons between the mice imaging and the biodistribution results showed a statistically significant correlation for the tumour activity (r = 0.999, P < 0.0001) and the tumour mass calculations (r = 0.977, P = 0.0008), whilst no correlation was found for the %IA/g (r = 0.521, P = 0.29). Median tumour-absorbed doses per injected activity of 52 cGy/MBq (range 36–69 cGy/MBq) and 649 cGy/MBq (range 441–950 cGy/MBq) were delivered by ¹¹¹In-labelled mAbs and extrapolated for ⁹⁰Y-labelled mAbs, respectively.

Conclusions

This study demonstrates the need for multidisciplinary efforts to standardise imaging and dosimetry protocols in pre-clinical imaging. Accurate image quantification can improve the calculation of the activity, %IA/g and absorbed dose. Diagnostic imaging could be used to estimate the injected activities required for therapeutic studies, potentially reducing the number of animals used.

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A novel 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivative inhibits tumor cell invasion and potentiates the apoptotic effect of TNFα by abrogating NF-κB activation cascade

Abstract

Condensed-bicyclic 4,6-substituted1,2,4-triazolo-1,3,4-thiadiazole derivatives (CBTT) have been shown to possess a wide spectrum of pharmacological activities. In this study, several novel CBTT derivatives were synthesized and investigated for their possible role as anti-neoplastic agents. The anti-proliferative effect of various CBTT derivatives was analyzed against tumor cell lines by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. One of the potential CBTT derivative, 5-(3-(2,3-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)flurobenzonitrile (DTTF) was found to be the most potent against cervical cancer SiHa cells and exhibited minimal effect against normal cells. Molecular docking analysis indicated that transcription factor NF-κB was one of the potential molecular targets modulated by DTTF. Specifically, the drug blocked the TNFα-induced phosphorylation of upstream IκBα kinase in a time-dependent manner leading to the suppression of NF-κB activation and nuclear translocation. DTTF also potentiated the apoptotic effect of TNFα, as well as significantly inhibited migration and invasion of tumor cells. Overall, these findings indicate a potential novel role and mechanism(s) of action of DTTF as an anticancer agent against diverse malignancies.

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Mille modis morimur : We die in a thousand ways

Abstract

Dying cells subjected to apoptotic programs are engulfed by neighboring cells or by professional phagocytes, without inflammation or immunological reactions in the tissue where apoptosis takes place. Apoptotic cells release danger-associated project signals to their neighbours, through different molecular patterns, stimulate antigen production and immune responses. Microenvironmental effects with several functional consequences indicate that cell death is a complex process and may take place in several ways. This idea is expressed by the title of the Special Issue and by the title of the guest editorial "Mille modis morimur" meaning that not only multicellular organisms, but also single cells may die in a thousand ways. This idea is demonstrated by the papers serving as examples for cell death. Apoptosis was induced by clary sage oil in Candida cells. Heavy metal (Gd) induced cell motility and apoptosis was found in mammalian cells. RNA oxidation enhanced the reversion frequency of apoptosis in yeast mutants. The frequency of apoptotic micronucleus formation increased in a concentration-dependent manner by methotrexate. The antioxidant coenzyme Q10 protected renal proximal tubule cells against nicotine-induced apoptosis. The synergy of 2-deoxy-d-glucose combined with berberine induced lysosome/autophagy. The mitochondrial apoptotic pathway could be regulated by glucocorticoid receptor in collaboration with Bcl-2 family proteins in developing T cells. Cylindrospermopsin induced biochemical changes led to apoptosis in plants. Mechanisms of stress seriously impacted the risk of apoptosis. Transcriptional control of apoptotic cell clearance was achieved by macrophage nuclear receptors. Finally, the clinical aspects of apoptosis-induced lymphopenia were reviewed in sepsis and other severe injuries. These examples not only support the view of many ways of cell death, but predict further potential ways to induce or reduce the risk of cell death.

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Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome

Abstract

Noonan syndrome is a genetic disorder with variable expression of distinctive facial features, webbed neck, chest deformity, short stature, cryptorchidism and congenital heart disease. The association of Noonan syndrome and giant cell granulomas of the mandible is widely reported. However, Noonan syndrome may also be associated with single or multifocal tenosynovial giant cell tumors, also referred to as pigmented villonodular synovitis. We report a child with Noonan syndrome, giant cell granulomas of the mandible and synovial and tenosynovial giant cell tumors involving multiple joints and tendon sheaths who was initially misdiagnosed with juvenile idiopathic arthritis. It is important for radiologists to be aware of the association of Noonan syndrome and multifocal giant cell lesions, which can range from the more commonly described giant cell granulomas of the mandible to isolated or multifocal intra- or extra-articular tenosynovial giant cell tumors or a combination of all of these lesions.

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Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome

Abstract

Noonan syndrome is a genetic disorder with variable expression of distinctive facial features, webbed neck, chest deformity, short stature, cryptorchidism and congenital heart disease. The association of Noonan syndrome and giant cell granulomas of the mandible is widely reported. However, Noonan syndrome may also be associated with single or multifocal tenosynovial giant cell tumors, also referred to as pigmented villonodular synovitis. We report a child with Noonan syndrome, giant cell granulomas of the mandible and synovial and tenosynovial giant cell tumors involving multiple joints and tendon sheaths who was initially misdiagnosed with juvenile idiopathic arthritis. It is important for radiologists to be aware of the association of Noonan syndrome and multifocal giant cell lesions, which can range from the more commonly described giant cell granulomas of the mandible to isolated or multifocal intra- or extra-articular tenosynovial giant cell tumors or a combination of all of these lesions.

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Imaging findings of adrenal primitive neuroectodermal tumors: a series of seven cases

Abstract

Objective

To explore the imaging features of adrenal primitive neuroectodermal tumors (PNETs).

Materials and methods

This retrospective study included seven patients with surgically and pathologically confirmed adrenal PNETs. Among them, six underwent computed tomography (CT) scans, and one underwent magnetic resonance imaging. The imaging findings, including size, shape, margin, hemorrhage, calcification, cystic degeneration, regional lymph nodes involvement, tumor thrombus formation and enhancement pattern, were retrospectively analyzed.

Results

Among the seven adrenal PNET patients, six were male, and one was female. The median age was 26 years (range 2–56 years). The disease generally presented with either insidious symptoms (n = 4) or non-specific symptoms, including right flank pain (n = 1) and left upper abdominal discomfort (n = 2). On the pre-enhanced CT images, the tumor usually appeared as a well-defined, rounded or oval, heterogeneous mass without calcification. Certain tissue characteristics, such as cystic degeneration (n = 5), capsule (n = 4) and hemorrhage (n = 2), were observed. Regional lymph node involvement was observed in three cases, and renal vein thrombus was observed in one case. All cases showed mild heterogeneous enhancement of the tumor on the enhanced CT images.

Conclusion

An adrenal PNET commonly presents as a relatively large, well-defined, heterogeneous mass with cystic degeneration, necrosis and a characteristic mild contrast-enhancement pattern on multiphase enhanced images. PNET should be considered when the diagnosis of common tumors is not favored by signs on images.

Clinical Trial Registration Statement

This study was approved by the medical ethics committee of Xiangya Hospital, Central South University. The approval number is 201512538.

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Imaging findings of adrenal primitive neuroectodermal tumors: a series of seven cases

Abstract

Objective

To explore the imaging features of adrenal primitive neuroectodermal tumors (PNETs).

Materials and methods

This retrospective study included seven patients with surgically and pathologically confirmed adrenal PNETs. Among them, six underwent computed tomography (CT) scans, and one underwent magnetic resonance imaging. The imaging findings, including size, shape, margin, hemorrhage, calcification, cystic degeneration, regional lymph nodes involvement, tumor thrombus formation and enhancement pattern, were retrospectively analyzed.

Results

Among the seven adrenal PNET patients, six were male, and one was female. The median age was 26 years (range 2–56 years). The disease generally presented with either insidious symptoms (n = 4) or non-specific symptoms, including right flank pain (n = 1) and left upper abdominal discomfort (n = 2). On the pre-enhanced CT images, the tumor usually appeared as a well-defined, rounded or oval, heterogeneous mass without calcification. Certain tissue characteristics, such as cystic degeneration (n = 5), capsule (n = 4) and hemorrhage (n = 2), were observed. Regional lymph node involvement was observed in three cases, and renal vein thrombus was observed in one case. All cases showed mild heterogeneous enhancement of the tumor on the enhanced CT images.

Conclusion

An adrenal PNET commonly presents as a relatively large, well-defined, heterogeneous mass with cystic degeneration, necrosis and a characteristic mild contrast-enhancement pattern on multiphase enhanced images. PNET should be considered when the diagnosis of common tumors is not favored by signs on images.

Clinical Trial Registration Statement

This study was approved by the medical ethics committee of Xiangya Hospital, Central South University. The approval number is 201512538.

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Dog ownership and physical activity among breast, prostate, and colorectal cancer survivors

Abstract

Background

Dog ownership has been associated with higher rates of physical activity (PA) in several populations but no study to date has focused on cancer survivors. The purpose of this study was to examine the associations between dog ownership and PA among cancer survivors; and to examine correlates of dog ownership.

Methods

A stratified random sample of 2062 breast (BCS), prostate (PCS), and colorectal cancer survivors (CRCS) was mailed a questionnaire assessing PA, social-cognitive, dog ownership, demographic, and medical variables.

Results

Overall, 25% of the sample were dog owners (DOs). There were no significant differences in moderate, vigorous or total PA minutes between DOs and non-dog owners (NDOs). There was a significant difference in light PA minutes in favor of DOs (153 vs. 112 minutes; 95% CI = +4 to +77; p = .030), however, this was largely restricted to BCS (143 vs. 79 minutes; 95% CI = +25 to +102; p = .001) who also reported fewer vigorous PA minutes (18 vs. 39 minutes; 95% CI = -42 to -1, p = .042). Survivors were more likely to be DOs if they had breast cancer (p = .054), a higher income (p = .021), radiation therapy (p = .029), chemotherapy (p = .010), were younger (p < .001), employed (p < .001), and a current smoker (p = .015). Few social cognitive variables were associated with DO.

Conclusions

Dog ownership among cancer survivors was not associated with moderate-to-vigorous PA, but was associated with light PA. Further research is necessary to determine if promoting dog ownership and dog walking among cancer survivors may increase PA and possibly improve health outcomes.

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