Randomized Controlled Trial of Hyalobarrier ® Versus No Hyalobarrier ® on the Ovulatory Status of Women with Periovarian Adhesions: A Pilot Study

Abstract

Introduction

Periadnexal adhesions are known to contribute to subfertility. The restoration of the tubo-ovarian anatomy is one the key principles in reproductive surgery, and this involves adhesiolysis. However, adhesion formation/reformation is very common after periovarian adhesiolysis. It is not known if the application of Hyalobarrier^®, an anti-adhesion gel, around the adnexal region postsurgery influences ovulatory status. The study is a pilot randomized controlled trial (RCT) randomizing women into the application of Hyalobarrier^® versus no Hyalobarrier^® at the time of laparoscopy, where postsurgical ovulatory status and pregnancy rates were evaluated.

Methods

This was a pilot RCT where women were recruited from the gynecological and subfertility clinic who were deemed to require an operative laparoscopy. If intraoperatively they were found to have periovarian adhesions, they were randomized into having adhesiolysis with and without usage of Hyalobarrier^®. Demographic details and intraoperative details including the severity, extent, and the ease of use of Hyalobarrier^® were recorded. Prior to the surgery and postoperatively, the participants had their serum hormonal status (day 2 FSH, LH and day 21 progesterone) evaluated. Postoperatively, they underwent a follicular tracking cycle at 3 months.

Results

Fifteen women were randomized into use of Hyalobarrier^® (study group) and 15 into the no Hyalobarrier^® group (control group) between December 2011 and January 2014. There was no difference in the patient characteristics in terms of age, BMI, the number of previous pregnancies, or the extent, site, and severity of adhesions between the two groups. There was no significant difference between the study versus control groups in terms of the hormonal profile (day 2 FSH and day 21 progesterone) before or after surgery. The 3-month postoperative day 10–12 follicular tracking findings and endometrial thickness were similar between the study and control groups. Four women were pregnant in the study group (24%) and one in the control group (7%) cumulatively over 2 years.

Conclusion

The use of Hyalobarrier^® post salpingo-ovariolysis did not influence follicular development as inferred from the results of the day 21 progesterone and folliculogram on day 10–12 3-month postsurgery.

Trial Registration

ISRCTN number, ISRCTN1833588.

Funding

Nordic Pharma.

from Cancer via ola Kala on Inoreader http://ift.tt/2fOF4vb
via IFTTT

Randomized Controlled Trial of Hyalobarrier ® Versus No Hyalobarrier ® on the Ovulatory Status of Women with Periovarian Adhesions: A Pilot Study

Abstract

Introduction

Periadnexal adhesions are known to contribute to subfertility. The restoration of the tubo-ovarian anatomy is one the key principles in reproductive surgery, and this involves adhesiolysis. However, adhesion formation/reformation is very common after periovarian adhesiolysis. It is not known if the application of Hyalobarrier^®, an anti-adhesion gel, around the adnexal region postsurgery influences ovulatory status. The study is a pilot randomized controlled trial (RCT) randomizing women into the application of Hyalobarrier^® versus no Hyalobarrier^® at the time of laparoscopy, where postsurgical ovulatory status and pregnancy rates were evaluated.

Methods

This was a pilot RCT where women were recruited from the gynecological and subfertility clinic who were deemed to require an operative laparoscopy. If intraoperatively they were found to have periovarian adhesions, they were randomized into having adhesiolysis with and without usage of Hyalobarrier^®. Demographic details and intraoperative details including the severity, extent, and the ease of use of Hyalobarrier^® were recorded. Prior to the surgery and postoperatively, the participants had their serum hormonal status (day 2 FSH, LH and day 21 progesterone) evaluated. Postoperatively, they underwent a follicular tracking cycle at 3 months.

Results

Fifteen women were randomized into use of Hyalobarrier^® (study group) and 15 into the no Hyalobarrier^® group (control group) between December 2011 and January 2014. There was no difference in the patient characteristics in terms of age, BMI, the number of previous pregnancies, or the extent, site, and severity of adhesions between the two groups. There was no significant difference between the study versus control groups in terms of the hormonal profile (day 2 FSH and day 21 progesterone) before or after surgery. The 3-month postoperative day 10–12 follicular tracking findings and endometrial thickness were similar between the study and control groups. Four women were pregnant in the study group (24%) and one in the control group (7%) cumulatively over 2 years.

Conclusion

The use of Hyalobarrier^® post salpingo-ovariolysis did not influence follicular development as inferred from the results of the day 21 progesterone and folliculogram on day 10–12 3-month postsurgery.

Trial Registration

ISRCTN number, ISRCTN1833588.

Funding

Nordic Pharma.

http://ift.tt/2fOF4vb

Bromodomain and extraterminal protein inhibitors in pediatrics: A review of the literature

Abstract

The last few years have seen the identification of pharmacologic approaches to target bromodomain and extraterminal (BET) proteins for cancer treatment. These proteins have an essential role in gene transcription regulation by binding acetylated lysine residues on histone tails, activating gene transcription. BET inhibitors have been tested in preclinical models including pediatric malignancies and several adult clinical trials are ongoing. Since the development of new drugs in pediatric cancer has long lagged behind programs for adults, the aim of this review is to show the importance of these therapies in pediatric malignancies to support their development in pediatric oncology/hematology.

http://ift.tt/2fKdMTi

Bromodomain and extraterminal protein inhibitors in pediatrics: A review of the literature

Abstract

The last few years have seen the identification of pharmacologic approaches to target bromodomain and extraterminal (BET) proteins for cancer treatment. These proteins have an essential role in gene transcription regulation by binding acetylated lysine residues on histone tails, activating gene transcription. BET inhibitors have been tested in preclinical models including pediatric malignancies and several adult clinical trials are ongoing. Since the development of new drugs in pediatric cancer has long lagged behind programs for adults, the aim of this review is to show the importance of these therapies in pediatric malignancies to support their development in pediatric oncology/hematology.

from Cancer via ola Kala on Inoreader http://ift.tt/2fKdMTi
via IFTTT

Erratum to: 53BP1 depletion causes PARP inhibitor resistance in ATM-deficient breast cancer cells

from Cancer via ola Kala on Inoreader http://ift.tt/2gEpZgY
via IFTTT

Alternative splicing of estrogen receptor alpha in hepatocellular carcinoma

Abstract

Background

The role of estrogen receptor alpha (ERa), estrogen receptor beta (ERb) and ERa36 signaling in hepatocellular carcinoma (HCC) is not fully addressed.

Methods

In this study, three cohorts were included: (i) primary HCC patients (N = 76, cohort P), (ii) colorectal liver metastasis (mCRC) (N = 32, cohort S), and (iii) HCC from The Cancer Genome Atlas (TCGA) (N = 121). The levels of ERa36 and wtER36 were measured and their correlation with clinicopathologic features was determined.

Results

WtERa was downregulated and that ERa36 was upregulated in tumor tissues in both cohort P and TCGA data set. ERa36 was downregulated in tumor tissues in cohort S. In cohort P, wtERa was differentially expressed in gender (P < 0.000), age (P = 0.004), tumor number (P = 0.043), tumor size (P = 0.002), intrahepatic recurrence (P = 0.054). ERa36 was unequally expressed in different non-tumor liver status (P = 0.040). WtERa was negatively associated with overall survival (OS) and disease free survival (DFS) in cohort P. Compared with non-tumor tissues, the expression of ERa36 was increased in primary HCC but decreased in secondary HCC, showing opposite expression patterns of ERa36 between primary HCC and secondary HCC.

Conclusions

Primary HCC is associated with the decreased WtERa but increased ERa36. The expression pattern of ERa36 is different between primary HCC and secondary HCC, as the former with the increased ERa36 but the latter with the decreased ERa36. Therefore, the expression of ERa36 may be used to differentiate the primary HCC and the secondary one.

from Cancer via ola Kala on Inoreader http://ift.tt/2fK7nr8
via IFTTT

Tumor characteristics and prognosis in familial breast cancer

Abstract

Background

Approximately 5–10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome.

Methods

We retrieved the clinical and biological data of 33 BRCA-positive, 66 BRCA-wild type and 1826 sporadic breast cancer patients contained in a single institution clinical database between 1980 and 2012. Specifically, we recorded age, tumor size, nodal status, treatment type, pattern of relapse, second primary incidence, outcome (disease-free survival and overall survival), and biological features (estrogen receptor [ER], progesterone receptor [PgR], tumor grade, proliferation and c-erbB2 status). Median follow-up was 70 months.

Results

BRCA-positive patients were significantly younger than sporadic breast cancer patients, and less likely to be ER-, PgR- or c-erbB2-positive than women with BRCA-wild type or sporadic breast cancer. Tumor size and grade, nodal status and proliferation did not differ among the three groups. Rates of radical mastectomy were 58, 42 and 37%, and those of conservative surgery were 42, 58 and 63% in women with BRCA-positive, BRCA-wild type and sporadic breast cancer (p = 0.03), respectively. The incidence of contralateral breast cancer was 12, 14 and 0% (p <0.0001) and the incidence of second primary tumors (non breast) was 9, 1 and 2% (p <0.0001) in BRCA-positive, BRCA-wild type and sporadic breast cancer, respectively. Median disease-free survival in years was 29 in BRCA-wild type, 19 in BRCA-positive and 14 in sporadic breast cancer patients (log-rank = 0.007). Median overall survival in years was not reached for BRCA-wild type, 19 for BRCA-positive and 13 for sporadic breast cancer patients (log-rank <0.0001). At multivariate analyses only BRCA-wild type status was related to a significant improvement in overall survival versus the sporadic breast cancer group (HR = 0,51; 95% CI (0,28–0,93) p = 0.028).

Conclusions

The biology and outcome of breast cancer differ between patients with BRCA mutations, patients with a family history but no BRCA mutations and patients with sporadic breast cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2gEyats
via IFTTT

Genetic polymorphisms of FAS and EVER genes in a Greek population and their susceptibility to cervical cancer: a case control study

Abstract

Background

The aim of the study was to evaluate the association of two SNPs of EVER1/2 genes' region (rs2290907, rs16970849) and the FAS-670 polymorphism with the susceptibility to precancerous lesions and cervical cancer in a Greek population.

Methods

Among the 515 women who were included in the statistical analysis, 113 belong to the case group and present with precancerous lesions or cervical cancer (27 with persistent CIN1, 66 with CIN2/3 and 20 with cervical cancer) and 402 belong to the control group. The chi-squared test was used to compare the case and the control groups with an allelic and a genotype-based analysis.

Results

The results of the statistical analysis comparing the case and the control groups for all the SNPs tested were not statistically significant. Borderline significant difference (p value = 0.079) was only found by the allelic model between the control group and the CIN1/CIN2 patients' subgroup for the polymorphism rs16970849. The comparison of the other case subgroups with the control group did not show any statistically significant difference.

Conclusions

None of the SNPs included in the study can be associated with statistical significance with the development of precancerous lesions or cervical cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2gExMLt
via IFTTT

Erratum to: 53BP1 depletion causes PARP inhibitor resistance in ATM-deficient breast cancer cells

http://ift.tt/2gEpZgY

Alternative splicing of estrogen receptor alpha in hepatocellular carcinoma

Abstract

Background

The role of estrogen receptor alpha (ERa), estrogen receptor beta (ERb) and ERa36 signaling in hepatocellular carcinoma (HCC) is not fully addressed.

Methods

In this study, three cohorts were included: (i) primary HCC patients (N = 76, cohort P), (ii) colorectal liver metastasis (mCRC) (N = 32, cohort S), and (iii) HCC from The Cancer Genome Atlas (TCGA) (N = 121). The levels of ERa36 and wtER36 were measured and their correlation with clinicopathologic features was determined.

Results

WtERa was downregulated and that ERa36 was upregulated in tumor tissues in both cohort P and TCGA data set. ERa36 was downregulated in tumor tissues in cohort S. In cohort P, wtERa was differentially expressed in gender (P < 0.000), age (P = 0.004), tumor number (P = 0.043), tumor size (P = 0.002), intrahepatic recurrence (P = 0.054). ERa36 was unequally expressed in different non-tumor liver status (P = 0.040). WtERa was negatively associated with overall survival (OS) and disease free survival (DFS) in cohort P. Compared with non-tumor tissues, the expression of ERa36 was increased in primary HCC but decreased in secondary HCC, showing opposite expression patterns of ERa36 between primary HCC and secondary HCC.

Conclusions

Primary HCC is associated with the decreased WtERa but increased ERa36. The expression pattern of ERa36 is different between primary HCC and secondary HCC, as the former with the increased ERa36 but the latter with the decreased ERa36. Therefore, the expression of ERa36 may be used to differentiate the primary HCC and the secondary one.

http://ift.tt/2fK7nr8

Tumor characteristics and prognosis in familial breast cancer

Abstract

Background

Approximately 5–10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome.

Methods

We retrieved the clinical and biological data of 33 BRCA-positive, 66 BRCA-wild type and 1826 sporadic breast cancer patients contained in a single institution clinical database between 1980 and 2012. Specifically, we recorded age, tumor size, nodal status, treatment type, pattern of relapse, second primary incidence, outcome (disease-free survival and overall survival), and biological features (estrogen receptor [ER], progesterone receptor [PgR], tumor grade, proliferation and c-erbB2 status). Median follow-up was 70 months.

Results

BRCA-positive patients were significantly younger than sporadic breast cancer patients, and less likely to be ER-, PgR- or c-erbB2-positive than women with BRCA-wild type or sporadic breast cancer. Tumor size and grade, nodal status and proliferation did not differ among the three groups. Rates of radical mastectomy were 58, 42 and 37%, and those of conservative surgery were 42, 58 and 63% in women with BRCA-positive, BRCA-wild type and sporadic breast cancer (p = 0.03), respectively. The incidence of contralateral breast cancer was 12, 14 and 0% (p <0.0001) and the incidence of second primary tumors (non breast) was 9, 1 and 2% (p <0.0001) in BRCA-positive, BRCA-wild type and sporadic breast cancer, respectively. Median disease-free survival in years was 29 in BRCA-wild type, 19 in BRCA-positive and 14 in sporadic breast cancer patients (log-rank = 0.007). Median overall survival in years was not reached for BRCA-wild type, 19 for BRCA-positive and 13 for sporadic breast cancer patients (log-rank <0.0001). At multivariate analyses only BRCA-wild type status was related to a significant improvement in overall survival versus the sporadic breast cancer group (HR = 0,51; 95% CI (0,28–0,93) p = 0.028).

Conclusions

The biology and outcome of breast cancer differ between patients with BRCA mutations, patients with a family history but no BRCA mutations and patients with sporadic breast cancer.

http://ift.tt/2gEyats

Genetic polymorphisms of FAS and EVER genes in a Greek population and their susceptibility to cervical cancer: a case control study

Abstract

Background

The aim of the study was to evaluate the association of two SNPs of EVER1/2 genes' region (rs2290907, rs16970849) and the FAS-670 polymorphism with the susceptibility to precancerous lesions and cervical cancer in a Greek population.

Methods

Among the 515 women who were included in the statistical analysis, 113 belong to the case group and present with precancerous lesions or cervical cancer (27 with persistent CIN1, 66 with CIN2/3 and 20 with cervical cancer) and 402 belong to the control group. The chi-squared test was used to compare the case and the control groups with an allelic and a genotype-based analysis.

Results

The results of the statistical analysis comparing the case and the control groups for all the SNPs tested were not statistically significant. Borderline significant difference (p value = 0.079) was only found by the allelic model between the control group and the CIN1/CIN2 patients' subgroup for the polymorphism rs16970849. The comparison of the other case subgroups with the control group did not show any statistically significant difference.

Conclusions

None of the SNPs included in the study can be associated with statistical significance with the development of precancerous lesions or cervical cancer.

http://ift.tt/2gExMLt

Illuminating a Risk for Breast Cancer: A Preliminary Ecological Study on the Association Between Streetlight and Breast Cancer

Artificial light at night (ALAN) for elongating photophase is a new source of pollution. We examined the association between measured ALAN levels and breast cancer (BC) standard morbidity ratio (SMR) at a statistical area (SA) level in an urban environment. Sample size consisted of 266 new BC cases ages 35-74. Light measurements (lux) were performed in 11 SAs. A new calculated variable of morbidity per SA size (SMR_35-74/km²) was correlated with the light variables per road length, using Pearson correlations (P < .05, 1-tailed). Looking for a light threshold, we correlated percentage of light points above SA light intensity median with SMR_35-74/km². SMR_35-74/km² was significantly and positively strongly correlated with mean, median, and standard-deviation (SD) light intensity per road length (r = .79, P < .01, R² = .63; r = .77, P < .01, R² = .59; and r = .79, P < .01, R² = .63). Light threshold results demonstrate a marginally significant positive moderate correlation between percentage of points above 16.3 lux and SMR_35-74/km² (r = .48, P < .07; R² = .23). In situ results support the hypothesis that outdoor ALAN illumination is associated with a higher BC-SMR in a specific area and age group. Moreover, we suggest an outdoor light threshold of approximately 16 lux as the minimal intensity to affect melatonin levels and BC morbidity. To the best of our knowledge, our attempt is the first to use this method and show such association between streetlight intensity and BC morbidity and therefore should be further developed.

http://ift.tt/2gvFEMJ

Illuminating a Risk for Breast Cancer: A Preliminary Ecological Study on the Association Between Streetlight and Breast Cancer

Artificial light at night (ALAN) for elongating photophase is a new source of pollution. We examined the association between measured ALAN levels and breast cancer (BC) standard morbidity ratio (SMR) at a statistical area (SA) level in an urban environment. Sample size consisted of 266 new BC cases ages 35-74. Light measurements (lux) were performed in 11 SAs. A new calculated variable of morbidity per SA size (SMR_35-74/km²) was correlated with the light variables per road length, using Pearson correlations (P < .05, 1-tailed). Looking for a light threshold, we correlated percentage of light points above SA light intensity median with SMR_35-74/km². SMR_35-74/km² was significantly and positively strongly correlated with mean, median, and standard-deviation (SD) light intensity per road length (r = .79, P < .01, R² = .63; r = .77, P < .01, R² = .59; and r = .79, P < .01, R² = .63). Light threshold results demonstrate a marginally significant positive moderate correlation between percentage of points above 16.3 lux and SMR_35-74/km² (r = .48, P < .07; R² = .23). In situ results support the hypothesis that outdoor ALAN illumination is associated with a higher BC-SMR in a specific area and age group. Moreover, we suggest an outdoor light threshold of approximately 16 lux as the minimal intensity to affect melatonin levels and BC morbidity. To the best of our knowledge, our attempt is the first to use this method and show such association between streetlight intensity and BC morbidity and therefore should be further developed.

from Cancer via ola Kala on Inoreader http://ift.tt/2gvFEMJ
via IFTTT

A metastatic mouse model identifies genes that regulate neuroblastoma metastasis

Metastatic relapse is the major cause of death in pediatric neuroblastoma (NB), where there remains a lack of therapies to target this stage of disease. To understand the molecular mechanisms mediating NB metastasis, we developed a mouse model using intracardiac injection and in vivo selection to isolate malignant cell subpopulations with a higher propensity for metastasis to bone and the central nervous system. Gene expression profiling revealed primary and metastatic cells as two distinct cell populations defined by differential expression 412 genes and multiple pathways, including CADM1, SPHK1 and YAP/TAZ whose expression independently predicted survival. In the metastatic subpopulations, a gene signature was defined (MET-75) that predicted survival of NB patients with metastatic disease. Mechanistic investigations demonstrated causal roles for CADM1, SPHK1 and YAP/TAZ in mediating metastatic phenotypes in vitro and in vivo. Notably, pharmcological targeting of SPHK1 or YAP/TAZ was sufficient to inhibit NB metastasis in vivo. Overall, our findings defined gene expression signatures and candidate therapeutics that could improve the treatment of metastatic NB.

http://ift.tt/2g4q1eu

Castration resistance in prostate cancer is mediated by the kinase NEK6

In prostate cancer, the development of castration resistance is pivotal in progression to aggressive disease. However, understanding of the pathways involved remains incomplete. In this study, we performed a high-throughput genetic screen to identify kinases that enable tumor formation by androgen-dependent prostate epithelial (LHSR-AR) cells under androgen-deprived conditions. In addition to the identification of known mediators of castration resistance, which served to validate the screen, we identified a mitotic-related serine/threonine kinase, NEK6, as a mediator of androgen-independent tumor growth. NEK6 was overexpressed in a subset of human prostate cancers. Silencing NEK6 in castration-resistant cancer cells was sufficient to restore sensitivity to castration in a mouse xenograft model system. Tumors in which castration resistance was conferred by NEK6 were predominantly squamous in histology with no evidence of AR signaling. Gene expression profiling suggested that NEK6 overexpression stimulated cytoskeletal, differentiation and immune signaling pathways and maintained gene expression patterns normal decreased by castration. Phosphoproteome profiling revealed the transcription factor FOXJ2 as a novel NEK6 substrate, with FOXJ2 phosphorylation associated with increased expression of newly identified NEK6 transcriptional targets. Overall, our studies establish NEK6 signaling as a central mechanism mediating castration-resistant prostate cancer.

http://ift.tt/2gi7Chf

Crystal structure of the emerging cancer target MTHFD2 in complex with a substrate-based inhibitor

To sustain their proliferation, cancer cells become dependent on one-carbon metabolism to support purine and thymidylate synthesis. Indeed, one of the most highly upregulated enzymes during neoplastic transformation is MTHFD2, a mitochondrial methylenetetrahydrofolate dehydrogenase and cyclohydrolase involved in one-carbon metabolism. Since MTHFD2 is expressed normally only during embryonic development, it offers a disease-selective therapeutic target for eradicating cancer cells while sparing healthy cells. Here we report the synthesis and preclinical characterization of the first inhibitor of human MTHFD2. We also disclose the first crystal structure of MTHFD2 in complex with a substrate-based inhibitor and the enzyme cofactors NAD+ and inorganic phosphate. Our work provides a rationale for continued development of a structural framework for the generation of potent and selective MTHFD2 inhibitors for cancer treatment.

http://ift.tt/2g4ozss

Transcriptional regulator CNOT3 defines an aggressive colorectal cancer subtype

Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent and impact of these alterations are still being unraveled. Here we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers (CRC), as compared to corresponding benign precursor adenomas. Modification of certain CRC sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC). In primary CRC cells, we observed a scattered pattern of CNOT3 expression, as might be expected for a tumor-initiating cell marker. CRC cells exhibited nuclear and cytoplasmic expression of CNOT3, suggesting possible roles in both transcription and mRNA stability. We found that CNOT3 was bound primarily to genes whose expression was affected by CNOT3 loss, and also at sites modulated in certain types of CRC. These target genes were implicated in ESC and cancer self-renewal and fell into two distinct groups: those dependent on CNOT3 and MYC for optimal transcription and those repressed by CNOT3 binding and promoter hypermethylation. Silencing CNOT3 in CRC cells resulted in replication arrest. In clinical specimens, early stage tumors that included >5% CNOT3+ cells exhibited a correlation to worse clinical outcomes compared to tumors with little to no CNOT3 expression. Together, our findings implicate CNOT3 in the coordination of colonic epithelial cell self-renewal, suggesting this factor as a new biomarker for molecular and prognostic classification of early-stage CRC.

http://ift.tt/2gi36z9

A metastatic mouse model identifies genes that regulate neuroblastoma metastasis

Metastatic relapse is the major cause of death in pediatric neuroblastoma (NB), where there remains a lack of therapies to target this stage of disease. To understand the molecular mechanisms mediating NB metastasis, we developed a mouse model using intracardiac injection and in vivo selection to isolate malignant cell subpopulations with a higher propensity for metastasis to bone and the central nervous system. Gene expression profiling revealed primary and metastatic cells as two distinct cell populations defined by differential expression 412 genes and multiple pathways, including CADM1, SPHK1 and YAP/TAZ whose expression independently predicted survival. In the metastatic subpopulations, a gene signature was defined (MET-75) that predicted survival of NB patients with metastatic disease. Mechanistic investigations demonstrated causal roles for CADM1, SPHK1 and YAP/TAZ in mediating metastatic phenotypes in vitro and in vivo. Notably, pharmcological targeting of SPHK1 or YAP/TAZ was sufficient to inhibit NB metastasis in vivo. Overall, our findings defined gene expression signatures and candidate therapeutics that could improve the treatment of metastatic NB.

from Cancer via ola Kala on Inoreader http://ift.tt/2g4q1eu
via IFTTT

Castration resistance in prostate cancer is mediated by the kinase NEK6

In prostate cancer, the development of castration resistance is pivotal in progression to aggressive disease. However, understanding of the pathways involved remains incomplete. In this study, we performed a high-throughput genetic screen to identify kinases that enable tumor formation by androgen-dependent prostate epithelial (LHSR-AR) cells under androgen-deprived conditions. In addition to the identification of known mediators of castration resistance, which served to validate the screen, we identified a mitotic-related serine/threonine kinase, NEK6, as a mediator of androgen-independent tumor growth. NEK6 was overexpressed in a subset of human prostate cancers. Silencing NEK6 in castration-resistant cancer cells was sufficient to restore sensitivity to castration in a mouse xenograft model system. Tumors in which castration resistance was conferred by NEK6 were predominantly squamous in histology with no evidence of AR signaling. Gene expression profiling suggested that NEK6 overexpression stimulated cytoskeletal, differentiation and immune signaling pathways and maintained gene expression patterns normal decreased by castration. Phosphoproteome profiling revealed the transcription factor FOXJ2 as a novel NEK6 substrate, with FOXJ2 phosphorylation associated with increased expression of newly identified NEK6 transcriptional targets. Overall, our studies establish NEK6 signaling as a central mechanism mediating castration-resistant prostate cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/2gi7Chf
via IFTTT

Crystal structure of the emerging cancer target MTHFD2 in complex with a substrate-based inhibitor

To sustain their proliferation, cancer cells become dependent on one-carbon metabolism to support purine and thymidylate synthesis. Indeed, one of the most highly upregulated enzymes during neoplastic transformation is MTHFD2, a mitochondrial methylenetetrahydrofolate dehydrogenase and cyclohydrolase involved in one-carbon metabolism. Since MTHFD2 is expressed normally only during embryonic development, it offers a disease-selective therapeutic target for eradicating cancer cells while sparing healthy cells. Here we report the synthesis and preclinical characterization of the first inhibitor of human MTHFD2. We also disclose the first crystal structure of MTHFD2 in complex with a substrate-based inhibitor and the enzyme cofactors NAD+ and inorganic phosphate. Our work provides a rationale for continued development of a structural framework for the generation of potent and selective MTHFD2 inhibitors for cancer treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/2g4ozss
via IFTTT

Transcriptional regulator CNOT3 defines an aggressive colorectal cancer subtype

Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent and impact of these alterations are still being unraveled. Here we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers (CRC), as compared to corresponding benign precursor adenomas. Modification of certain CRC sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC). In primary CRC cells, we observed a scattered pattern of CNOT3 expression, as might be expected for a tumor-initiating cell marker. CRC cells exhibited nuclear and cytoplasmic expression of CNOT3, suggesting possible roles in both transcription and mRNA stability. We found that CNOT3 was bound primarily to genes whose expression was affected by CNOT3 loss, and also at sites modulated in certain types of CRC. These target genes were implicated in ESC and cancer self-renewal and fell into two distinct groups: those dependent on CNOT3 and MYC for optimal transcription and those repressed by CNOT3 binding and promoter hypermethylation. Silencing CNOT3 in CRC cells resulted in replication arrest. In clinical specimens, early stage tumors that included >5% CNOT3+ cells exhibited a correlation to worse clinical outcomes compared to tumors with little to no CNOT3 expression. Together, our findings implicate CNOT3 in the coordination of colonic epithelial cell self-renewal, suggesting this factor as a new biomarker for molecular and prognostic classification of early-stage CRC.

from Cancer via ola Kala on Inoreader http://ift.tt/2gi36z9
via IFTTT

miR-15b Inhibits the Progression of Glioblastoma Cells Through Targeting Insulin-like Growth Factor Receptor 1

Abstract

The microRNAs (miRNAs) have been suggested as a tumor suppressor in recent years. miR-15b was reported to exert an anti-oncogenic role in the proliferation, migration, and invasion of diverse tumor cells. However, the mechanisms underlying miR-15b-mediated biology of glioblastoma are still unclear. In the present study, the expression of miR-15b was down-regulated in glioblastoma tumor tissues and U87 and U251 cells, but insulin-like growth factor receptor 1 (IGF1R) expression became up-regulated in these tumor tissues and cells (all p < 0.001). Furthermore, IGF1R expression was inversely associated with miR-15b expression. Notably, patients with lower miR-15b expression have a much shorter survival period compared with high expression (log-rank test p = 0.045). In vitro data demonstrated that miR-15b mimics inhibited the proliferation, cell cycle arrest, and invasion of U87 and U251 cells. Besides, we validated IGF1R as a direct target of miR-15b using dual luciferase assays, and IGF1R plasmids partially abrogated miR-15b mimics inhibited cell proliferation. In vivo, miR-15b mimics indeed repressed cell proliferation in mouse xenograft model. In conclusion, our study demonstrated that miR-15b inhibits the progression of glioblastoma cells through targeting IGF1R, and miR-15b can be recommended as a tumor suppressor in the progression of glioblastoma.

http://ift.tt/2gRopbS

miR-15b Inhibits the Progression of Glioblastoma Cells Through Targeting Insulin-like Growth Factor Receptor 1

Abstract

The microRNAs (miRNAs) have been suggested as a tumor suppressor in recent years. miR-15b was reported to exert an anti-oncogenic role in the proliferation, migration, and invasion of diverse tumor cells. However, the mechanisms underlying miR-15b-mediated biology of glioblastoma are still unclear. In the present study, the expression of miR-15b was down-regulated in glioblastoma tumor tissues and U87 and U251 cells, but insulin-like growth factor receptor 1 (IGF1R) expression became up-regulated in these tumor tissues and cells (all p < 0.001). Furthermore, IGF1R expression was inversely associated with miR-15b expression. Notably, patients with lower miR-15b expression have a much shorter survival period compared with high expression (log-rank test p = 0.045). In vitro data demonstrated that miR-15b mimics inhibited the proliferation, cell cycle arrest, and invasion of U87 and U251 cells. Besides, we validated IGF1R as a direct target of miR-15b using dual luciferase assays, and IGF1R plasmids partially abrogated miR-15b mimics inhibited cell proliferation. In vivo, miR-15b mimics indeed repressed cell proliferation in mouse xenograft model. In conclusion, our study demonstrated that miR-15b inhibits the progression of glioblastoma cells through targeting IGF1R, and miR-15b can be recommended as a tumor suppressor in the progression of glioblastoma.

from Cancer via ola Kala on Inoreader http://ift.tt/2gRopbS
via IFTTT

Mucoepidermoid Carcinoma of the Breast Found during Treatment of Lymphoma

A 71-year-old woman, previously treated for malignant lymphoma, was admitted to our hospital with a tumor in the right breast. The tumor size was 2.0 cm in diameter, and the borderline was unclear. The core needle biopsy material revealed an invasive adenocarcinoma with metaplastic change. Right mastectomy and sentinel lymph node biopsy was performed. Histologically, the tumor was composed of mucus-secreting, epidermoid, and intermediate cells. These findings confirmed the diagnosis as mucoepidermoid carcinoma (MEC) of the breast. MEC is more frequently observed in the salivary glands and occurs rarely in the breast, with an incidence of approximately 0.3% of all breast cancers. Because of the rarity of the disease, the clinicopathological features and clinical outcome have not been fully investigated. The relationship between MEC of the breast and lymphoma are unclear. Here we report a rare case of MEC of the breast.
Case Rep Oncol 2016;9:806–814

http://ift.tt/2grR9EX

Childhood Hypopigmented Mycosis Fungoides: A Rare Diagnosis

Primary cutaneous lymphomas (PCL) are rare in pediatrics. Mycosis fungoides (MF) is the most frequent PCL diagnosed in childhood. There are various clinical variants of MF, including the hypopigmented MF (HMF). We present a 5-year-old boy with an 18-month history of progressive, generalized, nonpruritic hypopigmented lesions with central lacy erythema. He had no improvement with emollients. Skin biopsy showed typical features of HMF. He was treated with topical corticosteroids and tacrolimus and narrow-band ultraviolet B (NBUVB) phototherapy, with good response. HMF may mimic multiple skin disorders. Unusual hypopigmented skin lesions should be biopsied. Though phototherapy is effective, recurrence is common.

http://ift.tt/2g0sqH7

Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiotherapy

Publication date: Available online 29 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sonal S. Noticewala, Nan Li, Casey W. Williamson, Carl K. Hoh, Hanjie Shen, Michael T. McHale, Cheryl C. Saenz, John Einck, Steven Plaxe, Florin Vaida, Catheryn M. Yashar, Loren K. Mell
Purpose/Objective(s)To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extra-pelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiotherapy (CRT).Materials/MethodsWe sampled 39 cervical cancer patients treated with CRT, of which 25 were treated with concurrent cisplatin (40 mg/m²) and 14 were treated with cisplatin (40 mg/m²)/ gemcitabine (50-125 mg/m²) (C/G). Patients underwent ¹⁸F-FDG-PET/CT imaging at baseline and 1.5-6.0 months post-treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extra-pelvic vs. pelvic ABM percent from baseline to post-treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extra-pelvic BM using a two-sided paired t-test.ResultsWe observed a significant increase in the overall extra-pelvic compensatory response following CRT (0.381; 95% CI: 0.312, 0.449), and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared to C/G (p=0.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (p<0.001) and C/G (p<0.001), while extra-pelvic ABM percentage was increased in patients receiving cisplatin (p<0.001) and C/G (p<0.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (p<0.001) and C/G (p<0.001). The mean SUV appeared lower in extra-pelvic structures after CRT in patients treated with C/G (p=0.076), but not with cisplatin (p=0.942). We also observed that older age and more intense chemotherapy regimens were correlated with a decreased compensatory response on multivariable analysis. In patient's treated with C/G, mean pelvic bone marrow dose was found to be negatively correlated with the compensatory response.ConclusionPatients have differing subacute compensatory responses after CRT, owing to variable recovery in unirradiated marrow. Intensive chemotherapy regimens appear to decrease the extra-pelvic compensatory response, which may lead to increased hematologic toxicity.



from Cancer via ola Kala on Inoreader http://ift.tt/2fHaal5
via IFTTT

Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiotherapy

Publication date: Available online 29 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sonal S. Noticewala, Nan Li, Casey W. Williamson, Carl K. Hoh, Hanjie Shen, Michael T. McHale, Cheryl C. Saenz, John Einck, Steven Plaxe, Florin Vaida, Catheryn M. Yashar, Loren K. Mell
Purpose/Objective(s)To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extra-pelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiotherapy (CRT).Materials/MethodsWe sampled 39 cervical cancer patients treated with CRT, of which 25 were treated with concurrent cisplatin (40 mg/m²) and 14 were treated with cisplatin (40 mg/m²)/ gemcitabine (50-125 mg/m²) (C/G). Patients underwent ¹⁸F-FDG-PET/CT imaging at baseline and 1.5-6.0 months post-treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV of the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extra-pelvic vs. pelvic ABM percent from baseline to post-treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extra-pelvic BM using a two-sided paired t-test.ResultsWe observed a significant increase in the overall extra-pelvic compensatory response following CRT (0.381; 95% CI: 0.312, 0.449), and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared to C/G (p=0.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (p<0.001) and C/G (p<0.001), while extra-pelvic ABM percentage was increased in patients receiving cisplatin (p<0.001) and C/G (p<0.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (p<0.001) and C/G (p<0.001). The mean SUV appeared lower in extra-pelvic structures after CRT in patients treated with C/G (p=0.076), but not with cisplatin (p=0.942). We also observed that older age and more intense chemotherapy regimens were correlated with a decreased compensatory response on multivariable analysis. In patient's treated with C/G, mean pelvic bone marrow dose was found to be negatively correlated with the compensatory response.ConclusionPatients have differing subacute compensatory responses after CRT, owing to variable recovery in unirradiated marrow. Intensive chemotherapy regimens appear to decrease the extra-pelvic compensatory response, which may lead to increased hematologic toxicity.



http://ift.tt/2fHaal5

Erratum to: The DNA methyltransferase inhibitor zebularine exerts antitumor effects and reveals BATF2 as a poor prognostic marker for childhood medulloblastoma

from Cancer via ola Kala on Inoreader http://ift.tt/2gR8muW
via IFTTT

Erratum to: The DNA methyltransferase inhibitor zebularine exerts antitumor effects and reveals BATF2 as a poor prognostic marker for childhood medulloblastoma

http://ift.tt/2gR8muW

Comprehensive DNA Methylation and Mutation Analyses Reveal a Methylation Signature in Colorectal Sessile Serrated Adenomas

Abstract

Colorectal sessile serrated adenomas (SSA) are hypothesized to be precursor lesions of an alternative, serrated pathway of colorectal cancer, abundant in genes with aberrant promoter DNA hypermethylation. In our present pilot study, we explored DNA methylation profiles and examined selected gene mutations in SSA. Biopsy samples from patients undergoing screening colonoscopy were obtained during endoscopic examination. After DNA isolation and quality analysis, SSAs (n = 4) and healthy controls (n = 5) were chosen for further analysis. DNA methylation status of 96 candidate genes was screened by q(RT)PCR using Methyl-Profiler PCR array system. Amplicons for 12 gene mutations were sequenced by GS Junior Instrument using ligated and barcoded adaptors. Analysis of DNA methylation revealed 9 hypermethylated genes in both normal and SSA samples. 12 genes (CALCA, DKK2, GALR2, OPCML, PCDH10, SFRP1, SFRP2, SLIT3, SST, TAC1, VIM, WIF1) were hypermethylated in all SSAs and 2 additional genes (BNC1 and PDLIM4) were hypermethylated in 3 out of 4 SSAs, but in none of the normal samples. 2 SSAs exhibited BRAF mutation and synchronous MLH1 hypermethylation and were microsatellite instable by immunohistochemical analysis. Our combined mutation and DNA methylation analysis revealed that there is a common DNA methylation signature present in pre-neoplastic SSAs. This study advocates for the use of DNA methylation as a potential biomarker for the detection of SSA; however, further investigation is needed to better characterize the molecular background of these newly recognized colorectal lesions.

http://ift.tt/2gAQBze

Comprehensive DNA Methylation and Mutation Analyses Reveal a Methylation Signature in Colorectal Sessile Serrated Adenomas

Abstract

Colorectal sessile serrated adenomas (SSA) are hypothesized to be precursor lesions of an alternative, serrated pathway of colorectal cancer, abundant in genes with aberrant promoter DNA hypermethylation. In our present pilot study, we explored DNA methylation profiles and examined selected gene mutations in SSA. Biopsy samples from patients undergoing screening colonoscopy were obtained during endoscopic examination. After DNA isolation and quality analysis, SSAs (n = 4) and healthy controls (n = 5) were chosen for further analysis. DNA methylation status of 96 candidate genes was screened by q(RT)PCR using Methyl-Profiler PCR array system. Amplicons for 12 gene mutations were sequenced by GS Junior Instrument using ligated and barcoded adaptors. Analysis of DNA methylation revealed 9 hypermethylated genes in both normal and SSA samples. 12 genes (CALCA, DKK2, GALR2, OPCML, PCDH10, SFRP1, SFRP2, SLIT3, SST, TAC1, VIM, WIF1) were hypermethylated in all SSAs and 2 additional genes (BNC1 and PDLIM4) were hypermethylated in 3 out of 4 SSAs, but in none of the normal samples. 2 SSAs exhibited BRAF mutation and synchronous MLH1 hypermethylation and were microsatellite instable by immunohistochemical analysis. Our combined mutation and DNA methylation analysis revealed that there is a common DNA methylation signature present in pre-neoplastic SSAs. This study advocates for the use of DNA methylation as a potential biomarker for the detection of SSA; however, further investigation is needed to better characterize the molecular background of these newly recognized colorectal lesions.

from Cancer via ola Kala on Inoreader http://ift.tt/2gAQBze
via IFTTT

Trends in published meta-analyses in cancer research, 2008–2013

Abstract

In order to capture trends in the contribution of epidemiology to cancer research, we describe an online meta-analysis database resource for cancer clinical and population research and illustrate trends and descriptive detail of cancer meta-analyses from 2008 through 2013. A total of 4,686 cancer meta-analyses met our inclusion criteria. During this 6-year period, a fivefold increase was observed in the yearly number of meta-analyses. Fifty-six percent of meta-analyses concerned observational studies, mostly of cancer risk, more than half of which were genetic studies. The major cancer sites were breast, colorectal, and digestive. This online database for Cancer Genomics and Epidemiology Navigator will be continuously updated to allow investigators to quickly navigate the meta-analyses emerging from cancer epidemiology studies and cancer clinical trials.

from Cancer via ola Kala on Inoreader http://ift.tt/2gR4eLb
via IFTTT

The Association Between Out-of-Pocket Costs and Adherence to Adjuvant Endocrine Therapy Among Newly Diagnosed Breast Cancer Patients.

Objective: To determine how out-of-pocket costs for adjuvant endocrine therapy (AET) medication affects adherence among newly diagnosed breast cancer survivors with private health insurance who initiate therapy. Materials and Methods: We examined medical and pharmacy claims for the 1-year period after initiating AET using the Truven Health Analytics MarketScan database. Adherence was defined as >=80% proportion of days covered. Mean out-of-pocket costs for AET fill were measured as the sum of copayments, coinsurance, and deductibles and adjusted to 30-day amounts. Using a multivariable logistic regression model we calculated adjusted risk ratios controlling for age, comorbidities, type of surgery, use of chemotherapy and/or radiation therapy, average out-of-pocket costs for other services, and pharmacy use characteristics. Results: Of the 6863 women 64 years and younger who were diagnosed with breast cancer and initiated AET, 73.9% were adherent (proportion of days covered>=80%). A total of 19% of patients had $20 were 6% to 8% less likely to be adherent compared with patients paying

from Cancer via ola Kala on Inoreader http://ift.tt/2fLtKzM
via IFTTT

An Oncologist's Perspective on the Affordable Care Act.

No abstract available

from Cancer via ola Kala on Inoreader http://ift.tt/2gruoAR
via IFTTT

Trends in published meta-analyses in cancer research, 2008–2013

Abstract

In order to capture trends in the contribution of epidemiology to cancer research, we describe an online meta-analysis database resource for cancer clinical and population research and illustrate trends and descriptive detail of cancer meta-analyses from 2008 through 2013. A total of 4,686 cancer meta-analyses met our inclusion criteria. During this 6-year period, a fivefold increase was observed in the yearly number of meta-analyses. Fifty-six percent of meta-analyses concerned observational studies, mostly of cancer risk, more than half of which were genetic studies. The major cancer sites were breast, colorectal, and digestive. This online database for Cancer Genomics and Epidemiology Navigator will be continuously updated to allow investigators to quickly navigate the meta-analyses emerging from cancer epidemiology studies and cancer clinical trials.

http://ift.tt/2gR4eLb

The Association Between Out-of-Pocket Costs and Adherence to Adjuvant Endocrine Therapy Among Newly Diagnosed Breast Cancer Patients.

Objective: To determine how out-of-pocket costs for adjuvant endocrine therapy (AET) medication affects adherence among newly diagnosed breast cancer survivors with private health insurance who initiate therapy. Materials and Methods: We examined medical and pharmacy claims for the 1-year period after initiating AET using the Truven Health Analytics MarketScan database. Adherence was defined as >=80% proportion of days covered. Mean out-of-pocket costs for AET fill were measured as the sum of copayments, coinsurance, and deductibles and adjusted to 30-day amounts. Using a multivariable logistic regression model we calculated adjusted risk ratios controlling for age, comorbidities, type of surgery, use of chemotherapy and/or radiation therapy, average out-of-pocket costs for other services, and pharmacy use characteristics. Results: Of the 6863 women 64 years and younger who were diagnosed with breast cancer and initiated AET, 73.9% were adherent (proportion of days covered>=80%). A total of 19% of patients had $20 were 6% to 8% less likely to be adherent compared with patients paying

http://ift.tt/2fLtKzM

An Oncologist's Perspective on the Affordable Care Act.

No abstract available

http://ift.tt/2gruoAR

Assessing colonic anatomy normal values based on air contrast enemas in children younger than 6 years

Abstract

Background

Contrast enemas with barium or water-soluble contrast agents are sometimes performed in children with severe intractable constipation to identify anatomical abnormalities. However there are no clear definitions for normal colonic size or abnormalities such as colonic dilation or sigmoid redundancy in children.

Objective

To describe characteristics of colonic anatomy on air contrast enemas in children without constipation to provide normal values for colonic size ratios in children.

Materials and methods

We performed a retrospective chart review of children aged 0–5 years who had undergone air contrast enemas for intussusception. The primary outcome measures were the ratios of the diameters and lengths of predetermined colonic segments (lengths of rectosigmoid and descending colon; diameters of rectum, sigmoid, descending colon, transverse colon and ascending colon) in relation to the L2 vertebral body width.

Results

We included 119 children (median age 2.0 years, range 0–5 years, 68% boys). Colonic segment length ratios did not change significantly with age, although the differences for the rectosigmoid/L2 ratio were borderline significant (P = 0.05). The ratios that involved the rectal and ascending colon diameters increased significantly with age, while diameter ratios involving the other colonic segments did not. Differences by gender and race were not significant.

Conclusion

These data can be used for reference purposes in young children undergoing contrast studies of the colon.

http://ift.tt/2fH16wk

Assessing colonic anatomy normal values based on air contrast enemas in children younger than 6 years

Abstract

Background

Contrast enemas with barium or water-soluble contrast agents are sometimes performed in children with severe intractable constipation to identify anatomical abnormalities. However there are no clear definitions for normal colonic size or abnormalities such as colonic dilation or sigmoid redundancy in children.

Objective

To describe characteristics of colonic anatomy on air contrast enemas in children without constipation to provide normal values for colonic size ratios in children.

Materials and methods

We performed a retrospective chart review of children aged 0–5 years who had undergone air contrast enemas for intussusception. The primary outcome measures were the ratios of the diameters and lengths of predetermined colonic segments (lengths of rectosigmoid and descending colon; diameters of rectum, sigmoid, descending colon, transverse colon and ascending colon) in relation to the L2 vertebral body width.

Results

We included 119 children (median age 2.0 years, range 0–5 years, 68% boys). Colonic segment length ratios did not change significantly with age, although the differences for the rectosigmoid/L2 ratio were borderline significant (P = 0.05). The ratios that involved the rectal and ascending colon diameters increased significantly with age, while diameter ratios involving the other colonic segments did not. Differences by gender and race were not significant.

Conclusion

These data can be used for reference purposes in young children undergoing contrast studies of the colon.

from Cancer via ola Kala on Inoreader http://ift.tt/2fH16wk
via IFTTT

Feasibility and clinical integration of molecular profiling for target identification in pediatric solid tumors

Abstract

Background

The role of tumor molecular profiling in directing targeted therapy utilization remains to be defined for pediatric tumors. We aimed to evaluate the feasibility of a sequencing and molecular biology tumor board (MBB) program, and its clinical impact on children with solid tumors.

Procedure

We report on a single-center MBB experience of 60 pediatric patients with a poor prognosis or relapsed/refractory solid tumors screened between October 2014 and November 2015. Tumor molecular profiling was performed with panel-based next-generation sequencing and array comparative genomic hybridization.

Results

Mean age was 12 ± 5.7 years (range 0.1–21.5); main tumor types were high-grade gliomas (n = 14), rare sarcomas (n = 9), and neuroblastomas (n = 8). The indication was a poor prognosis tumor at diagnosis for 16 patients and relapsed (n = 26) or refractory disease (n = 18) for the remaining 44 patients. Molecular profiling was feasible in 58 patients. Twenty-three patients (40%) had a potentially actionable finding. Patients with high-grade gliomas had the highest number of targetable alterations (57%). Six of the 23 patients subsequently received a matched targeted therapy for a period ranging from 16 days to 11 months. The main reasons for not receiving targeted therapy were poor general condition (n = 5), pursuit of conventional therapy (n = 6), or lack of pediatric trial (n = 4).

Conclusions

Pediatric molecular profiling is feasible, with more than a third of patients being eligible to receive targeted therapy, yet only a small proportion were treated with these therapies. Analysis at diagnosis may be useful for children with very poor prognosis tumsors.

http://ift.tt/2fLhRdi

Feasibility and clinical integration of molecular profiling for target identification in pediatric solid tumors

Abstract

Background

The role of tumor molecular profiling in directing targeted therapy utilization remains to be defined for pediatric tumors. We aimed to evaluate the feasibility of a sequencing and molecular biology tumor board (MBB) program, and its clinical impact on children with solid tumors.

Procedure

We report on a single-center MBB experience of 60 pediatric patients with a poor prognosis or relapsed/refractory solid tumors screened between October 2014 and November 2015. Tumor molecular profiling was performed with panel-based next-generation sequencing and array comparative genomic hybridization.

Results

Mean age was 12 ± 5.7 years (range 0.1–21.5); main tumor types were high-grade gliomas (n = 14), rare sarcomas (n = 9), and neuroblastomas (n = 8). The indication was a poor prognosis tumor at diagnosis for 16 patients and relapsed (n = 26) or refractory disease (n = 18) for the remaining 44 patients. Molecular profiling was feasible in 58 patients. Twenty-three patients (40%) had a potentially actionable finding. Patients with high-grade gliomas had the highest number of targetable alterations (57%). Six of the 23 patients subsequently received a matched targeted therapy for a period ranging from 16 days to 11 months. The main reasons for not receiving targeted therapy were poor general condition (n = 5), pursuit of conventional therapy (n = 6), or lack of pediatric trial (n = 4).

Conclusions

Pediatric molecular profiling is feasible, with more than a third of patients being eligible to receive targeted therapy, yet only a small proportion were treated with these therapies. Analysis at diagnosis may be useful for children with very poor prognosis tumsors.

from Cancer via ola Kala on Inoreader http://ift.tt/2fLhRdi
via IFTTT