Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τρίτη 31 Μαΐου 2016
Impact of socio-economic position on cancer stage at presentation: Findings from a large hospital-based study in Germany
Abstract
We explored the relationship between socio-economic characteristics and cancer stage at presentation. Patients admitted to a university hospital for diagnosis and treatment of cancer provided data on their education, vocational training, income, employment, job, health insurance, and postcode. Tumour stage was classified according to the Union International Contre le Cancer (UICC). To analyse disparities in the likelihood of late-stage (UICC III/IV vs. I/II) diagnoses, logistic regression models adjusting for age and gender were used.
Out of 1,012 patients, 572 (59%) had late-stage cancer. Separately tested, increased odds of advanced disease were associated with post-compulsory education compared to college degrees, with apprenticeship and no vocational training, with unemployment, disability pension, jobs with a low hierarchy level, blue collar jobs and with low income. Health insurance and community size were not related with late-stage cancer. Jointly modelled, there was evidence for an independent effect of unemployment (odds ratio (OR) 1.7, CI 1.0-2.8), disability pension (OR 1.8, CI 1.0-3.2), and very low income (OR 2.6, CI 1.1.-6.1) on the likelihood of advanced disease stage.
It is of great concern that these socio-economic gradients occur even in systems with equal access to health care. This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/1RJGf6O
via IFTTT
Concurrent radiotherapy and intrathecal methotrexate for treating leptomeningeal metastasis from solid tumors with adverse prognostic factors: A prospective and single-arm study
Abstract
The prognosis of leptomeningeal metastasis (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. In this phase II clinical trial, we evaluated the efficacy and safety of intrathecal chemotherapy (IC) combined with concomitant involved-field radiotherapy (IF-RT) for treating LM from solid tumors with adverse prognostic factors. Fifty-nine patients with LM from various solid tumors were enrolled between May 2010 and December 2014. Concurrent therapy consisted of concomitant IC (methotrexate 12.5-15 mg and dexamethasone 5 mg, weekly) and IF-RT (whole brain and/or spinal canal RT, 40 Gy/20f). For patients with low Karnofsky performance status (KPS) score and radiotherapy intolerance, induction IC (1-3 times) was given before concurrent therapy. Thirty-eight patients (64.4%) received subsequent treatments. All patients were followed up at least 6 months after LM diagnosis or until death. Primary endpoint evaluated was clinical response rate. Secondary endpoints were overall survival (OS) and safety. The pathological types included lung cancer (n=42), breast cancer (n=11) and others (n=6). Median KPS score was 40 (range 20-70). Fifty-one patients (86.4%) completed concurrent therapy. The overall response rate was 86.4% (51/59). OS ranged from 0.4 to 36.7 months (median 6.5 months), and 1-year-survival rate was 21.3%. Treatment-related adverse events mainly included acute meningitis, chronic delayed encephalopathy, radiculitis, myelosuppression, and mucositis. Twelve patients (20.3%) had grade III-V toxic reactions. We concluded that IC combined with concomitant IF-RT, with significant efficacy and acceptable toxicity, may be an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors. This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/1XcpH00
via IFTTT
International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007
Abstract
Primary liver cancer, the most common histologic types of which are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the second leading cause of cancer death worldwide. While rising incidence of liver cancer in low-risk areas and decreasing incidence in some high-risk areas has been reported, trends have not been thoroughly explored by country or by histologic type. We examined liver cancer incidence overall and by histology by calendar time and birth cohort for selected countries between 1978 and 2007. For each successive 5-year period, age-standardized incidence rates were calculated from volumes V-IX of the Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume X) database. Wide global variations persist in liver cancer incidence. Rates of liver cancer remain highest in Asian countries, specifically Eastern and South-Eastern Asian countries. While rates in most of these high-risk countries have been decreasing in recent years, rates in India and several low-risk countries of Africa, Europe, the Americas, and Oceania have been on the rise. Liver cancer rates by histologic type tend to convey a similar temporal profile. However, in Thailand, France, and Italy, ICC rates have increased while HCC rates have declined. We expect rates in high-risk countries to continue to decrease, as the population seroprevalence of hepatitis B virus (HBV) continues to decline. In low-risk countries, targeted screening and treatment of the hepatitis C virus (HCV), treatment of diabetes and primary prevention of obesity, will be key in reducing future liver cancer incidence. This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/1RJFU4f
via IFTTT
The comparison of clinical and biological characteristics between IDH1 and IDH2 mutations in gliomas
Abstract
Background
Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are frequent in low-grade gliomas and secondary glioblastomas (sGBM). Because they yield the same oncometabolite, D-2-hydroxyglutarate, they are often treated as equivalent and pooled. The objective of this study was to provide insight into the differences between IDH1 and IDH2 mutant gliomas.
Methods
To investigate the different clinical and molecular characterization between IDH1 mutant and IDH2 mutant gliomas, we studied 811 patients with IDH1 mutations, IDH2 mutations and IDH1/2 wild-type. In addition, whole-transcriptome sequencing and DNA methylation data were used to assess the distribution of genetic changes in IDH1 and IDH2 mutant gliomas in a Chinese population-based cohort.
Results
Among 811 gliomas in our cohort, 448 cases (55.2 %) harbored an IDH1 mutation, 18 cases (2.2 %) harbored an IDH2 mutation and 345 cases (42.6 %) harbored an IDH1/2 wild-type. We found that IDH1 and IDH2 are mutually exclusive in gliomas, and IDH2 mutations are mutually exclusive with PTEN, P53 and ATRX mutations. Patients with IDH2 mutations had a higher frequency of 1p/19q co-deletion (p < 0.05) than IDH1 mutant patients. In addition, a Gene Set Enrichment Analysis (GSEA) showed that IDH2 mutant gliomas were associated with the oxidative phosphorylation gene set, and the four most representative biological processes for genes commonly altered by hypermethylation in IDH2 mutant gliomas were the regulation of cell proliferation, cell motion, cell migration and response to hypoxia. Patients with IDH2 mutant gliomas exhibited longer Overall survival (OS) (p < 0.05) and longer Progression-free survival (PFS) (p < 0.05) than patients with IDH1/2 wild-type gliomas. However, their OS and PFS did not differ from that of IDH1 mutant patients.
Conclusions
Our study revealed an intrinsic distinction between IDH1 and IDH2 mutant gliomas, and these mutations should be considered separately because their differences could have implications for the diagnosis and treatment of IDH1/2 mutant gliomas.
from Cancer via ola Kala on Inoreader http://ift.tt/25yK8c5
via IFTTT
Impact of hypofractionated and standard fractionated chemoradiation before pancreatoduodenectomy for pancreatic ductal adenocarcinoma
BACKGROUND
Previous studies have suggested that preoperative chemoradiation (CRT) is associated with an improved margin-negative resection rate among patients who undergo pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, the optimal preoperative regimen has not been established.
METHODS
All patients with PDAC who received chemotherapy and/or CRT followed by PD between 1999 and 2014 were retrospectively reviewed. The effects of 2 external-beam radiation regimens—a standard course of 50.4 Gy in 28 fractions and a hypofractionated course of 30 Gy in 10 fractions—were compared. Differences in clinicopathologic characteristics, locoregional recurrence (LR), and overall survival (OS) were assessed.
RESULTS
Among 472 patients who received preoperative therapy, 224 (47.5%) received 30 Gy, 221 (46.8%) received 50.4 Gy, and 27 (5.7%) received chemotherapy alone. Patients who received 50.4 Gy were more likely to have advanced-stage disease and to have received induction and postoperative chemotherapy, but there was no difference in the R1 margin status, treatment effect, LR, or OS between the 2 radiation groups (all P values > .05). Patients who received preoperative CRT had a lower rate of LR than patients who received preoperative chemotherapy alone (P < .01). In a multivariate Cox proportional hazards analysis, 50.4 Gy was associated with OS and LR similar to those associated with 30 Gy, whereas the absence of preoperative radiation was associated with a higher rate of LR (odds ratio, 2.21; 95% confidence interval, 1.04-4.70) and similar OS.
CONCLUSIONS
Preoperative hypofractionated CRT was associated with similar local control and OS in comparison with standard CRT in patients undergoing PD for PDAC. The use of chemotherapy alone without CRT was associated with poorer local control but similar survival. Cancer 2016. © 2016 American Cancer Society.
from Cancer via ola Kala on Inoreader http://ift.tt/1ZaKJcC
via IFTTT
Comparative effectiveness of surgical and nonsurgical therapy for advanced laryngeal cancer
BACKGROUND
The treatment of patients with advanced stage laryngeal cancer includes surgery or concurrent chemoradiation (CRT). Although CRT has become more common in recent years, to the authors' knowledge, the effectiveness of complete CRT in improving survival over surgery has not been studied.
METHODS
The authors examined patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare claims-linked data set with locoregional laryngeal cancer who were diagnosed between 1997 and 2007. Multivariate Cox proportional hazard analyses were conducted to compare overall and cause-specific 5-year survival rates between treatment modalities, adjusting for patient sociodemographic and clinical characteristics. A propensity score-matched subcohort also was used to compare survival.
RESULTS
Of the 3212 patients in the study cohort, 42% underwent surgery and 18% underwent CRT. Only approximately one-quarter of patients who were treated with CRT completed the courses. In adjusted analyses, the authors were unable to reject the null hypothesis of no difference in 5-year all-cause or cause-specific mortality risk between patients treated with surgery and patients undergoing complete CRT (hazards ratio, 1.25 [95% confidence interval, 0.91-1.71; P = .16] and hazard ratio, 1.41 [95% confidence interval, 0.9-2.2; P = .14], respectively). Older age, not currently married, Medicaid eligibility, and prior cancer history were found to be associated with a higher risk of mortality (P<.05).
CONCLUSIONS
Patients with advanced laryngeal cancer who underwent complete CRT were found to have overall and cause-specific survival rates similar to those of patients undergoing surgery. However, a substantial percentage of patients who initiated CRT did not complete the course. Although CRT provides organ preservation, the benefits and trade-offs of CRT and total laryngectomy should be discussed fully with patients. The importance of completing the full course of CRT should be emphasized. Cancer 2016. © 2016 American Cancer Society.
from Cancer via ola Kala on Inoreader http://ift.tt/1WuXoZZ
via IFTTT
Emerging trends in surgical and adjuvant radiation therapies among women diagnosed with ductal carcinoma in situ
BACKGROUND
The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors.
METHODS
Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression.
RESULTS
DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups.
CONCLUSIONS
Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society.
from Cancer via ola Kala on Inoreader http://ift.tt/1ZaKmig
via IFTTT
Ductal carcinoma in situ: How much is too much?
In this issue of Cancer, Shiyanbola et al describe changing trends in the treatment of ductal carcinoma in situ. Their findings reinforce the need for research into the natural history of ductal carcinoma in situ that may enable women with low-risk lesions to undergo less invasive treatment. See also pages 000-000.
from Cancer via ola Kala on Inoreader http://ift.tt/1WuXeSt
via IFTTT
Malignancy-associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes
BACKGROUND
Malignancy-associated hemophagocytic lymphohistiocytosis (HLH) in adults is a highly lethal disorder. Knowledge gaps have resulted in under diagnosis or delayed diagnosis.
METHODS
The University of Texas MD Anderson Cancer Center pathology database (1991-2014) was retrospectively interrogated for the keywords "hemophagocytosis" and/or "lymphohistiocytosis." Seventy-seven adult patients were identified. All had an underlying malignancy. Sixteen patients who had insufficient documentation were excluded.
RESULTS
The majority of patients who had pathologic evidence of hemophagocytosis/lymphohistiocytosis had an incomplete workup to confirm or refute HLH using the 2004 HLH criteria (HLH-2004; n = 8 variables), which is a common problem in adult HLH. Only 13 of 61 patients (21%) met the HLH-2004 diagnostic criteria based on available retrospective data. To identify potentially missed cases of HLH, the published literature was reviewed, and selected additional variables known to be associated with adult HLH were selected, resulting in extended diagnostic criteria of 18 variables. Thirty-five patients met the extended criteria, and 33 had follow-up data available. The median overall survival of the 13 patients who met both the extended criteria and the HLH-2004 criteria was similar to that of the 20 patients who met the extended criteria but NOT the HLH-2004 criteria (1.43 vs 1.76 months, respectively; P = .34) indicating a similar underlying, aggressive, systemic process. Twenty-six patients did not meet either criteria, and 17 had follow-up data available. The median overall survival of the 17 patients who had pathologic hemophagocytosis or lymphohistiocytosis but met neither criteria was significantly superior to the survival of those who met both the extended criteria and the HLH-2004 criteria and those who met the extended criteria but not the HLH-2004 criteria (17.27 vs 1.43 vs 1.76, respectively; P = .002).
CONCLUSIONS
The addition of diagnostic laboratory variables that are more easily and rapidly available in smaller institutions and primary care settings than the HLH-2004 variables may be a good surrogate to raise early suspicion of malignancy-associated HLH. Prospective validation is warranted. Cancer 2016. © 2016 American Cancer Society.
from Cancer via ola Kala on Inoreader http://ift.tt/1ZaKIW6
via IFTTT
Increased incidence of FBXW7 and POLE proofreading domain mutations in young adult colorectal cancers
BACKGROUND
The incidence and outcomes of patients with colorectal cancer (CRC) varies by age. Younger patients tend to have sporadic cancers that are not detected by screening and worse survival. To understand whether genetic differences exist between age cohorts, the authors sought to characterize unique genetic alterations in patients with CRC.
METHODS
In total, 283 patients who were diagnosed with sporadic CRC between 1998 and 2010 were identified and divided by age into 2 cohorts—ages ≤45 years (the younger cohort) and ≥65 years (the older cohort)—and targeted exome sequencing was performed. The Fisher exact test was used to detect differences in mutation frequencies between the 2 groups. Whole exome sequencing was performed on 21 additional younger patient samples for validation. Findings were confirmed in The Cancer Genome Atlas CRC data set.
RESULTS
In total, 246 samples were included for final analysis (195 from the older cohort and 51 from the younger cohort). Mutations in the FBXW7 gene were more common in the younger cohort (27.5% vs 9.7%; P = .0022) as were mutations in the proofreading domain of polymerase ε catalytic subunit (POLE) (9.8% vs 1%; P = .0048). There were similar mutation rates between cohorts with regard to TP53 (64.7% vs 61.5%), KRAS (43.1% vs 46.2%), and APC (60.8% vs 73.8%). BRAF mutations were numerically more common in the older cohort, although the difference did not reach statistical significance (2% vs 9.7%; P = .082).
CONCLUSIONS
In this retrospective study, a unique genetic profile was identified for younger patients who have CRC compared with patients who are diagnosed at an older age. These findings should be validated in a larger study and could have an impact on future screening and treatment modalities for younger patients with CRC. Cancer 2016. © 2016 American Cancer Society.
from Cancer via ola Kala on Inoreader http://ift.tt/1WuXgK5
via IFTTT
Codon 13 KRAS mutation predicts patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases
BACKGROUND
Investigations regarding the impact of tumor biology after surgical management of colorectal liver metastasis have focused largely on overall survival. We investigated the impact of codon-specific KRAS mutations on the rates and patterns of recurrence in patients after surgery for colorectal liver metastasis (CRLM).
METHODS
All patients who underwent curative-intent surgery for CRLM between 2002 and 2015 at Johns Hopkins who had available data on KRAS mutation status were identified. Clinico-pathologic data, recurrence patterns, and recurrence-free survival (RFS) were assessed using univariable and multivariable analyses.
RESULTS
A total of 512 patients underwent resection only (83.2%) or resection plus radiofrequency ablation (16.8%). Although 5-year overall survival was 64.6%, 284 (55.5%) patients recurred with a median RFS time of 18.1 months. The liver was the initial recurrence site for 181 patients, whereas extrahepatic recurrence was observed in 162 patients. Among patients with an extrahepatic recurrence, 102 (63%) had a lung recurrence. Although overall KRAS mutation was not associated with overall RFS (P = 0.186), it was independently associated with a worse extrahepatic (P = 0.004) and lung RFS (P = 0.007). Among patients with known KRAS codon-specific mutations, patients with codon 13 KRAS mutation had a worse 5-year extrahepatic RFS (P = 0.01, whereas codon 12 mutations were not associated with extrahepatic (P = 0.11) or lung-specific recurrence rate (P = 0.24). On multivariable analysis, only codon 13 mutation independently predicted worse overall extrahepatic RFS (P = 0.004) and lung-specific RFS (P = 0.023).
CONCLUSIONS
Among patients undergoing resection of CRLM, overall KRAS mutation was not associated with RFS. KRAS codon 13 mutations, but not codon 12 mutations, were associated with a higher risk for overall extrahepatic recurrence and lung-specific recurrence. Cancer 2016. © 2016 American Cancer Society.
from Cancer via ola Kala on Inoreader http://ift.tt/1ZaK8Yy
via IFTTT
Accuracy of urinary human papillomavirus testing for the presence of cervical human papillomaviruses and higher grades of cervical intraepithelial neoplasia
BACKGROUND
Although urine-based testing for human papillomavirus (HPV) is being explored as a practical approach for cervical cancer screening, whether the results differ by age, race, or indicators of excess body weight or in populations exposed to HPV vaccines has not been documented by previous studies. The purpose of this study was to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and high-grade cervical intraepithelial lesions (grade 2 and 3 cervical intraepithelial neoplasia [CIN]) by the aforementioned population characteristics.
METHODS
The study population consisted of 502 women diagnosed with different grades of CIN. HPV testing was performed with paired urine and cervical cell DNA with the Roche Diagnostics Linear Array test. Agreement coefficient 1 and probabilities were calculated to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and CIN lesions.
RESULTS
Substantial to almost perfect agreement (0.66-0.83) was observed in the detection of any HPV genotype in urine specimens versus cervical specimens, regardless of the population characteristics. Although the positive predictive value for the detection of CIN lesions was relatively low, the negative predictive value for CIN-3 was high (≥90%) among women positive for any of the urinary or cervical high-risk human papillomavirus (HR-HPV) genotypes or HPV genotypes not included in currently available HPV vaccines.
CONCLUSIONS
The results demonstrate that urinary HPV testing provides highly satisfactory results for excluding the possibility of any cervical HPV infections, including HPV types not included in vaccines and CIN lesions associated with any HR-HPV, regardless of a woman's age, race, or excess body weight. Cancer 2016. © 2016 American Cancer Society.
from Cancer via ola Kala on Inoreader http://ift.tt/1WuXocG
via IFTTT
Helping parents live with the hole in their heart: The role of health care providers and institutions in the bereaved parents' grief journeys
BACKGROUND
Bereaved parents experience significant psychosocial and health sequelae, suggesting that this population may benefit from the ongoing extension of support and resources throughout the grief journey. The interaction of hospital staff with patients and families at the end of a child's life and after death profoundly affects parental grief, offering a unique opportunity for the medical community to positively impact the bereavement experience. The current study was conducted to explore the role of the health care team and medical institutions in the grief journeys of parents whose child died a cancer-related death.
METHODS
Eleven bereaved parents participated in 2 focus groups. Responses to each of the 3 main prompts were coded and analyzed independently using semantic content analysis techniques.
RESULTS
Four main concepts were identified within the parental narratives, including the importance of strong and ongoing relationships between providers and bereaved families, the importance of high-quality communication, the effect of negative experiences between providers and families on parental grief, and the importance of the institution's role in the grief journeys of bereaved parents.
CONCLUSIONS
Bereaved parents consistently identified the critical role played by medical staff and medical institutions throughout the grief journey. Key components of bereavement support identified by parents should serve to guide the actions of providers as well as provide a template for the development of a comprehensive bereavement program within an institution. Cancer 2016. © 2016 American Cancer Society.
from Cancer via ola Kala on Inoreader http://ift.tt/1ZaKyOr
via IFTTT
Cross-talk between the Tissue Factor/coagulation factor VIIa complex and the tyrosine kinase receptor EphA2 in cancer
Abstract
Background
Tissue Factor (TF) forms a proteolytically active complex together with coagulation factor VIIa (FVIIa) and functions as the trigger of blood coagulation or alternatively activates cell signaling. We recently described that EphA2 of the Eph tyrosine kinase receptor family is cleaved directly by the TF/FVIIa complex. The aim of the present study was to further characterize the cross-talk between TF/FVIIa and EphA2 using in vitro model systems and human cancer specimens.
Methods
Cleavage and phosphorylation of EphA2 was studied by Western blot. Subcellular localization of TF and EphA2 was investigated by a proximity ligation assay and confocal microscopy. Phalloidin staining of the actin cytoskeleton was used to study cell rounding and retraction fiber formation. Expression of TF and EphA2 in human colorectal cancer specimens was examined by immunohistochemistry.
Results
TF and EphA2 co-localized constitutively in MDA-MB-231 cells, and addition of FVIIa resulted in cleavage of EphA2 by a PAR2-independent mechanism. Overexpression of TF in U251 glioblastoma cells lead to co-localization with EphA2 at the leading edge and FVIIa-dependent cleavage of EphA2. FVIIa potentiated ephrin-A1-induced cell rounding and retraction fiber formation in MDA-MB-231 cells through a RhoA/ROCK-dependent pathway that did not require PAR2-activation. TF and EphA2 were expressed in colorectal cancer specimens, and were significantly correlated.
Conclusions
These results suggest that TF/FVIIa-EphA2 cross-talk might potentiate ligand-dependent EphA2 signaling in human cancers, and provide initial evidence that it is possible for this interaction to occur in vivo.
from Cancer via ola Kala on Inoreader http://ift.tt/1WuXyR9
via IFTTT
Endometrial cancer treated with levonorgestrel-releasing intrauterine device for almost three years in an elderly woman with comorbidity
Summary
In this case report we describe the treatment of a 95-year-old woman with endometrioid adenocarcinoma. She suffered from cardiovascular comorbidity and did not want surgical treatment. Instead a levonorgestrel-releasing intrauterine device (Mirena) was inserted. She had progression of the tumor but with a minimum of symptoms and side effects. At the final examination there were no signs of extra uterine disease. The levonorgestrel-releasing intrauterine device may be an acceptable alternative to surgery in severely comorbid patients, or if the patient refuses surgical treatment.
from Cancer via ola Kala on Inoreader http://ift.tt/1Xc9cRK
via IFTTT
Cristacarpin promotes ER stress-mediated ROS generation leading to premature senescence by activation of p21 waf-1
Abstract
Stress-induced premature senescence (SIPS) is quite similar to replicative senescence that is committed by cells exposed to various stress conditions viz. ultraviolet radiation (DNA damage), hydrogen peroxide (oxidative stress), chemotherapeutic agents (cytotoxic threat), etc. Here, we report that cristacarpin, a natural product obtained from the stem bark of Erythrina suberosa, promotes endoplasmic reticulum (ER) stress, leading to sub-lethal reactive oxygen species (ROS) generation and which eventually terminates by triggering senescence in pancreatic and breast cancer cells through blocking the cell cycle in the G1 phase. The majority of cristacarpin-treated cells responded to conventional SA-β-gal stains; showed characteristic p21waf1 upregulation along with enlarged and flattened morphology; and increased volume, granularity, and formation of heterochromatin foci—all of these features are the hallmarks of senescence. Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly reduced the expression of p21waf1, confirming that the modulation in p21waf1 by anti-proliferative cristacarpin was ROS dependent. Further, the elevation in p21waf1 expression in PANC-1 and MCF-7 cells was consistent with the decrease in the expression of Cdk-2 and cyclinD1. Here, we provide evidence that cristacarpin promotes senescence in a p53-independent manner. Moreover, cristacarpin treatment induced p38MAPK, indicating the ROS-dependent activation of the MAP kinase pathway, and thus abrogates the tumor growth in mouse allograft tumor model.
from Cancer via ola Kala on Inoreader http://ift.tt/1TV31yq
via IFTTT
Correlation of clinical outcomes with bremsstrahlung and Y-90 PET/CT imaging findings following Y-90 radiosynoviorthesis: a prospective study
Abstract
Background
It is unclear how to predict which patients will respond to Y-90 radiosynoviorthesis. The aim of this study is to correlate clinical outcomes following Y-90 radiosynoviorthesis with bremsstrahlung and Y-90 PET/CT imaging findings.
Methods
Fifty-one joints underwent bremsstrahlung planar and Y-90 PET/CT imaging following Y-90 radiosynoviorthesis. The Y-90 distribution pattern on bremsstrahlung planar imaging was classified as diffuse or non-diffuse and compared with the intra or extra-articular location of activity on Y-90 PET/CT. Treatment response was assessed by patients and clinicians at 6 months. In patients who underwent bremsstrahlung SPECT, side-by-side comparison with PET was performed with image quality/resolution scored using a five-point-scale.
Findings
Bremsstrahlung planar images were classified as diffuse in 33/51 (65 %) and non-diffuse in 18/51 (35 %) scans. There was no association between treatment response and the bremsstrahlung planar imaging pattern. PET/CT confirmed an intra-articular location in all 33/33 (100 %) diffuse scans and an extra-articular location in 3/18 (17 %) non-diffuse scans. Of the three joints with extra-articular activity, none had any treatment response. Excluding these three joints, there remained no association between the bremsstrahlung planar imaging pattern and treatment response. Of the 42 joints imaged with SPECT, PET image quality/resolution was classified as superior in 40 (95 %). In one patient with extra-articular activity on PET/CT, SPECT/CT was unable to definitively localise the activity to the intra or extra-articular space.
Conclusions
The distribution pattern on bremsstrahlung planar imaging did not correlate with clinical outcome following Y-90 radiosynoviorthesis in our study population. However, in patients with non-diffuse planar imaging patterns, Y-90 PET/CT should be considered to exclude extra-articular activity with PET providing superior image quality compared to SPECT.
from Cancer via ola Kala on Inoreader http://ift.tt/1TVh5bj
via IFTTT
Sialylation: an Avenue to Target Cancer Cells
Abstract
Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoproteins and glycolipids. The expression of sialylated glycoconjugates has been shown to change during development, differentiation, disease and oncogenic transformation. Abnormal sialylation in cancer cell is a distinctive feature associated with malignant properties including invasiveness and metastatic potential. The alterations in sialylation is accompanied by changes in sialic acid, sialidase activity, sialyltransferase (ST) activity or sialoproteins. The present review summarizes the reports on alterations of sialic acid, linkage specific STs and sialoproteins, sialidase activity together with different subtypes of ST and sialidases mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is governed by levels of sialidases and STs. Various types of STs are also involved in formation of different types sialylated tumor associated carbohydrate antigens which plays important role in metastasis. The alterations associated with sialylation aids in early diagnosis, prognosis and post treatment monitoring in various cancers. Recently newer drugs targeting different interplays of sialylation have been developed, which might have profound effect in inhibiting sialylation and thus cancer metastasis and infiltration.
from Cancer via ola Kala on Inoreader http://ift.tt/1r0prTr
via IFTTT
Mutation Scanning of D1705 and D1709 in the RNAse IIIb Domain of MicroRNA Processing Enzyme Dicer in Cutaneous Melanoma
Abstract
Since the discovery of microRNAs (miRNAs) there have been performed several studies showing perturbations in the expression of miRNAs and the miRNA expression machinery in cutaneous melanoma. Dicer, a pivotal cytosolic enzyme of miRNA maturation has shown to be affected by both somatic and germline mutations in a variety of cancers. Recent studies have shown that recurrent somatic mutations of Dicer frequently affect the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain, therefore called hot spot mutations. The present study investigates metal-ion-binding sites D1709 and D1705 of the Dicer RNase IIIb domain in cutaneous melanomas and melanoma metastasis by Sanger sequencing. All investigated samples showed wildtype sequence and no single mutation was detected. The miRNA processing enzyme Dicer of melanoma and melanoma metastasis does not appear to be affected by mutation in the metal-ion-binding sites D1709 and D1705 of its RNase IIIb domain.
from Cancer via ola Kala on Inoreader http://ift.tt/280Im2f
via IFTTT
Immunohistochemical Analysis of E-Cadherin, p53 and Inhibin-α Expression in Hydatidiform Mole and Hydropic Abortion
Abstract
The purpose of this study was to investigate the role of E-cadherin, p53, and inhibin-α immunostaining in the differential diagnosis of hydropic abortion (HA), partial hydatidiform mole (PHM), and complete hydatidiform mole (CHM). E-cadherin, p53, and inhibin-α protein expression patterns were investigated immunohistochemically using paraffin -embedded tissue sections from histologically diagnosed cases of HA (n = 23), PHM (n = 24), and CHM (n = 23). Expression patterns of these markers were scored semi-quantitatively according to the staining intensity, percentage of positive cells, and immunoreactivity score. Classification of cases was established on histologic criteria and supported by the molecular genotyping. Immunostaining allowed the identification of specific cell types with E-cadherin, p53, and inhibin-α expression in all cases. E-cadherin expression was detected on the cell surface of villous cytotrophoblasts. We observed a marked decline in the expression of E-cadherin from HAs to PHMs to CHMs. The p53-positive reaction was restricted to the nucleus of villous cytotrophoblasts. Significantly increased p53 expression was observed in CHMs, compared with HAs and PHMs. The expression of inhibin-α was localised in the cytoplasm of villous syncytiotrophoblasts, and the expression of this marker was significantly higher in PHMs and CHMs than HAs. In conclusion, immunohistochemical analysis of E-cadherin, p53, and inhibin-α expression could serve as a useful adjunct to conventional methods in the differential diagnosis of HA, PHM, and CHM.
from Cancer via ola Kala on Inoreader http://ift.tt/1r0p9fb
via IFTTT
Study on the Association Between miRNA-202 Expression and Drug Sensitivity in Multiple Myeloma Cells
Abstract
An increasing amount of experimental evidence has shown that miRNAs play a causal role in hematologic tumorigenesis. In this study, we characterized the role of miR-202 in multiple myeloma (MM) drug sensitivity. The potential binding site of miR-202 and B cell-activating factor (BAFF) was confirmed by luciferase reporter assay. MM cells were transfected with miR-202 mimics and inhibitor. Cells growth was measured by WST-1 cell proliferation assay and Annexin V-FLUOS apoptosis assay. BAFF and miR-202 mRNA levels were measured by real-time PCR. Meanwhile, BAFF, Bcl-2 family survival proteins and MAPK pathway proteins were measured by Western blot. It was found that miR-202 was functioned as a modulator of BAFF expression. miR-202 over-expression sensitized MM cells to bortezomib (Bort) but less to Thalidomide (Thal) and dexamethasone (Dex). miR-202 mimics in combination with Bort inhibited MM cell survival more effectively as compared with Bort treatment alone. Our study also provided experimental evidence that JNK/SAPK signaling pathway was involved in the regulatory effect of miR-202 on drug resistance of MM cells. These results suggest that the regulatory mechanism of miR-202 expression may be a promising target for fine-tuning anti-myeloma therapy.
from Cancer via ola Kala on Inoreader http://ift.tt/280IzSY
via IFTTT
Clinical Performance of APTIMA Human Papillomavirus (HPV) 16 18/45 mRNA Genotyping Testing for the Detection of Cervical Intraepithelial Neoplasia 3 (CIN3) or Cancer in a Select Group of Chinese Women
Abstract
HPV type was evaluated in a select group of Chinese women that were positive with hybrid capture, and correlations were performed between the pathology found, the type of virus and a semiquantitation from the hybrid capture results. Totally 394 referred high-risk-HPV-positive women evaluated by Hybrid Capture 2 (HC-2) assay were enrolled. Before colposcopy, cervical specimens were collected from all participants and suspended into PreservCytcollection medium (Hologic Inc., Marlborough, MA), and tested with the APTIMA HPV16 18/45 mRNA assay. Colposcopy and diagnostic biopsies were done on all participants. Viral load was assessed by HC2 assay. Totally 55 women were diagnosed as CIN 3 plus cancer (≥CIN3), and the prevalence of HPV16/18/45 was 65.5 % (95 % confidence interval [CI], 52.9–78.0 %) among these ≥CIN3 women. Compared with the group with positive HC2 but negative HPV16/18/45, the odds ratio (OR) to identify ≥CIN3 was 6.3 (95 % CI, 3.2–12.3) for HPV16 and 3.2 (95 % CI, 1.4–7.2) for HPV18/45. When using ≥CIN3 as an endpoint, the sensitivity and specificity was 65.5 % (95 % CI, 52.9–78.0 %) and 72.0 % (95 % CI, 67.2–76.8 %). In the case of HPV16/18/45 negative, no high HPV load had a statistically significant increased risk for the prevalence of ≥CIN3. HPV16, 18 and 45 infection is a major cause for ≥CIN3 in Chinese women. Women with positive HPV16/18/45 should be referred to colposcopy immediately. HPV load was not suitable for the further triaged of the HPV16/18/45 negative cases.
from Cancer via ola Kala on Inoreader http://ift.tt/1r0pfUc
via IFTTT
Serum Sialyl-Tn (STN) as a Tumor Marker in Patients with Endometrial Cancer
Abstract
There are no potential tumor markers validated for prognosis of endometrial cancer. However, sialyl Tn (STN) is a carbohydrate antigen that is associated with the production of mucin, which reportedly plays important roles in carcinogenesis. Although STN expression in endometrial cancer has been investigated, its prognostic value remains controversial and no studies have investigated serum STN levels in large case series. In this study, we investigated diagnostic and prognostic applications of serum STN for endometrial cancer. Between January 2006 and December 2012, serum STN levels were examined prospectively in patients with endometrial cancer. A total of 146 patients (stage I, 98; stage II, 15; stage III, 17; stage IV, 16) were treated for endometrial cancer. The median age was 60 years (28–83). Subsequently 29 patients (19.9%) relapsed at the time of the last follow-up and the median follow-up time was 44 months (1–83). Elevated serum STN levels were identified in 36 patients (24.7%) and were associated with histological grade (p = 0.02) and lymph node metastasis (p = 0.006). Elevated serum STN levels were not related to histological types, clinical stages, myometrial invasions, distant metastases, age, menopausal status, body mass index, or relapse. Among the 36 patients with elevated serum STN levels, 33 (91.7%) achieved remission and serum STN levels returned to the normal range. Seven patients (21.2%) with elevated serum STN levels at baseline relapsed and their serum STN levels were again elevated. Serum STN levels are a potential prognostic indicator for endometrial cancer.
from Cancer via ola Kala on Inoreader http://ift.tt/280Ir5Q
via IFTTT
Loss of Protein Tyrosine Phosphatase Receptor J Expression Predicts an Aggressive Clinical Course in Patients with Esophageal Squamous Cell Carcinoma
Abstract
Protein Tyrosine Phosphatase Receptor J (PTPRJ) has been reported to be a tumor suppressor in various human cancers. The aim of this study was to investigate the clinical significance of PTPRJ in ESCC patients and its effects on biological behaviors of ESCC cells. PTPRJ expression, at mRNA and protein levels, were respectively detected by quantitative real-time PCR, western blot and immunohistochemistry, based on 106 newly diagnosed ESCC patients. The associations between PTPRJ expression and clinicopathological characteristics of ESCC patients were statistically analyzed. Then, the effects of PTPRJ in migration and invasion were determined by wound healing and transwell assays based on ESCC cell line transfected with siRNA or expression vector of PTPRJ. Expression of PTPRJ at mRNA and protein levels were both significantly lower in ESCC tissues than those in normal esophageal mucosa. Immunohistochemistry showed that PTPRJ protein was localized in the cytoplasm of cancer cells in ESCC tissues. In addition, PTPRJ downregulation was found to be closely correlated with advanced tumor stage (P = 0.01) and poor differentiation (P = 0.03). Moreover, knockdown of PTPRJ in KYSE510 cells could significantly promote cell migration and invasion (both P < 0.05), which were reversed by the restoration of PTPRJ expression in vitro (both P < 0.05). Our data offer the convincing evidence that loss of PTPRJ expression may predict an aggressive clinical course in ESCC patients. PTPRJ may function as a tumor suppressor and play an important role in the regulation of ESCC cell motility, suggesting its potentials as a therapeutic agent for human ESCC.
from Cancer via ola Kala on Inoreader http://ift.tt/1r0oOt4
via IFTTT
miRNA Isolation from FFPET Specimen: A Technical Comparison of miRNA and Total RNA Isolation Methods
Abstract
MiRNA remain stable for detection and PCR-based amplification in FFPE tissue samples. Several miRNA extraction kits are available, however miRNA fraction, as part of total RNA can be isolated using total RNA purification methods, as well. Our primary aim was to compare four different miRNA and total RNA isolation methods from FFPE tissues. Further purposes were to evaluate quantitatively and qualitatively the yield of the isolated miRNA. MiRNAs were isolated from normal colorectal cancer FFPE specimens from the same patients. Two miRNA isolation kits (High Pure miRNA Isolation Kit, miRCURY™ RNA Isolation Kit) and two total RNA isolation kits were compared (High Pure RNA Paraffin Kit, MagNA Pure 96 Cellular RNA LV Kit). Quantity and quality were determined, expression analysis was performed by real-time PCR using qPCR Human Panel I + II (Exiqon) method detecting 742 human miRNAs in parallel. The yield of total RNA was found to be higher than miRNA purification protocols (in CRC: Ex: 0203 ± 0021 μg; HPm: 1,45 ± 0,8 μg; HPp: 21,36 ± 4,98 μg; MP: 8,6 ± 5,1 μg). MiRNAs were detected in lower relative quantity of total RNA compared to the miRNA kits. Higher number of miRNAs could be detected by the miRNA isolation kits in comparison to the total RNA isolation methods. (Ex: 497 ± 16; HPm: 542 ± 11; HPp: 332 ± 36; MP: 295 ± 74). Colon specific miRNAs (miR-21-5p;-34-5p) give satisfying results by miRNA isolation kits. Although miRNA can be detected also after total RNA isolation methods, for reliable and reproducible miRNA expression profiling the use of miRNA isolation kits are more suitable.
from Cancer via ola Kala on Inoreader http://ift.tt/280IChF
via IFTTT
Potential efficacy of therapies targeting intrahepatic lesions after sorafenib treatment of patients with hepatocellular carcinoma
Abstract
Background
We investigated the contribution of subsequent therapy for advanced hepatocellular carcinoma refractory or intolerant to sorafenib. Further, we investigated the impact of sorafenib on overall survival using individual data.
Methods
We reviewed the medical records of patients with advanced hepatocellular carcinoma treated with sorafenib. Survival after sorafenib treatment and overall survival were defined as the time when we discovered that patients were either refractory or intolerant to sorafenib and the period from the start of sorafenib treatment, respectively, until death during the study. We compared patients' prognoses according to their subsequent treatment as follows: group A, therapies targeting intrahepatic lesions; group B, systemic therapies alone; group C, no subsequent therapy. We used linear regression analysis to determine whether there was an association with survival after sorafenib treatment and with overall survival.
Results
Of 79 patients, 63 (79.7 %) received one or more subsequent therapies (44 and 19 patients in groups A and B, respectively). The five patients who survived more than two years after sorafenib treatment was discontinued responded to therapies targeting intrahepatic lesions. The median survival times of groups A, B, and C were 11.9 months, 5.8 months, and 3.6 months, respectively. Multivariate analysis revealed that group A, Child-Pugh score, serum α-fetoprotein level, and cause of failure of sorafenib treatment were independent prognostic factors for survival after sorafenib treatment. Individual survival after sorafenib treatment correlated highly with overall survival.
Conclusions
Targeting intrahepatic lesions may be useful for treating patients with advanced hepatocellular carcinoma patients after sorafenib treatment is discontinued.
from Cancer via ola Kala on Inoreader http://ift.tt/1Uakr6r
via IFTTT
ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours
Abstract
Background
Patients with metastatic colorectal cancer whose disease has progressed on oxaliplatin- and irinotecan-containing regimens may benefit from EGFR-inhibiting monoclonal antibodies if they do not contain mutations in the KRAS gene (are "wild type"). It is unknown whether these antibodies, such as cetuximab, are more efficacious in refractory metastatic colorectal cancer as monotherapy, or in combination with irinotecan. Lack of mutation in KRAS, BRAF and PIK3CA predicts response to EFGR-inhibitors. The ICECREAM trial examines the question of monotherapy versus combination with chemotherapy in two groups of patients: those with a "quadruple wild type" tumour genotype (no mutations in KRAS, NRAS, PI3KCA or BRAF genes) and those with the specific KRAS mutation in codon G13D, for whom possibly EGFR-inhibitor efficacy may be equivalent.
Methods and design
ICECREAM is a randomised, phase II, open-label, controlled trial comparing the efficacy of cetuximab alone or with irinotecan in patients with "quadruple wild type" or G13D-mutated metastatic colorectal cancer, whose disease has progressed on, or who are intolerant of oxaliplatin- and fluoropyrimidine-based chemotherapy. The primary endpoint is the 6-month progression-free survival benefit of the treatment regimen. Secondary endpoints are response rate, overall survival, and quality of life. The tertiary endpoint is prediction of outcome with further biological markers. International collaboration has facilitated recruitment in this prospective trial of treatment in these infrequently found molecular subsets of colorectal cancer.
Discussion
This unique trial will yield prospective information on the efficacy of cetuximab and whether this is further enhanced with chemotherapy in two distinct populations of patients with metastatic colorectal cancer: the "quadruple wild type", which may 'superselect' for tumours sensitive to EGFR-inhibition, and the rare KRAS G13D mutated tumours, which are also postulated to be sensitive to the drug. The focus on establishing both positive and negative predictive factors for the response to targeted therapy is an attempt to improve outcomes, reduce toxicity and contain treatment costs. Tissue and blood will yield a resource for molecular studies. Recruitment, particularly of patients with the rare G13D mutation, will demonstrate the ability for international collaboration to run prospective trials in small colorectal cancer molecular subgroups.
Trial registration
Australian and New Zealand Clinical Trials Registry: ACTRN12612000901808, registered 16 August 2012.
from Cancer via ola Kala on Inoreader http://ift.tt/1WWlpJz
via IFTTT
Assessment of laparoscopic stomach preserving surgery with sentinel basin dissection versus standard gastrectomy with lymphadenectomy in early gastric cancer–A multicenter randomized phase III clinical trial (SENORITA trial) protocol
Abstract
Background
Along with the marked increase in early gastric cancer (EGC) in the Eastern countries, there has been an effort to adopt the sentinel node concept in EGC to preserve gastric function and reduce the occurrence of postoperative complications. Based on promising results from a previous quality control study, this prospective multicenter randomized controlled phase III clinical trial aims to elucidate the oncologic safety of laparoscopic stomach-preserving surgery with sentinel basin dissection (SBD) compared to a standard laparoscopic gastrectomy.
Methods/Design
This trial is an investigator-initiated, open-label, multicenter randomized controlled phase III trial with a non-inferiority design. Patients diagnosed with a single lesion of clinical stage T1N0M0 gastric adenocarcinoma, with a diameter of 3 cm or less are eligible for the present study. A total of 580 patients (290 per group) will be randomized to either laparoscopic stomach-preserving surgery with SBD or standard surgery. The primary end-point is 3-year disease-free survival (DFS) and the secondary endpoints include postoperative morbidity and mortality, quality of life, 5-year DFS, and overall survival. Qualified investigators who completed the prior quality control study are exclusively allowed to participate in this phase III clinical trial.
Discussion
The proposed trial is expected to verify whether laparoscopic stomach-preserving surgery with SBD achieves similar oncologic outcomes and improved quality of life compared to a standard gastrectomy in EGC patients.
Trial registration
This study was registered at the NIH ClinicalTrial.gov database (NCT01804998) on March 4th, 2013.
from Cancer via ola Kala on Inoreader http://ift.tt/1WWlmxk
via IFTTT
Genomic Profiling and Directed Ex Vivo Drug Analysis of an Unclassifiable Myelodysplastic/Myeloproliferative Neoplasm Progressing into Acute Myeloid Leukemia
Abstract
Myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are rare genetically heterogeneous hematologic diseases associated with older age and a poor prognosis. If the disease progresses into acute myeloid leukemia (AML), it is often refractory to treatment. To gain insight into genetic alterations associated with disease progression, we used whole exome sequencing and single nucleotide polymorphism arrays to characterize the bone marrow and blood samples from a 39-year-old woman at MDS/MPN-U diagnosis and at AML progression, in which routine genetic diagnostics had not identified any genetic alterations. Our data revealed the presence of a partial tandem duplication of the MLL gene as the only detectable copy number change and 11 non-silent somatic mutations, includingDNMT3A R882H and NRAS G13D. All somatic lesions were present both at initial MDS/MPN-U diagnosis and at AML presentation at similar mutant allele frequencies. The patient has since had two extramedullary relapses and is at high risk of a future bone marrow relapse. A directed ex vivo drug sensitivity analysis showed that the patient's AML cells are sensitive to, e.g., the MEK inhibitor trametinib and the proteasome inhibitor bortezomib, indicating that she may benefit from treatment with these drugs. This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/1XLwb4t
via IFTTT
Dietary inflammatory index and prostate cancer survival
Abstract
Systemic inflammatory status has been reported to impact survival of prostate cancer (PCa) patients; however, evidence is lacking on whether the inflammatory potential of diet can influence prognosis of PCa patients. To investigate the association between a dietary inflammatory index (DII) and PCa survival, we conducted a retrospective cohort study including 726 men with PCa originally enrolled, between 1995 and 2002, in an Italian case-control study. Information on diet and Gleason score was collected at PCa diagnosis. DII was derived from a food-frequency questionnaire using a validated algorithm. Adjusted hazard ratios (HRs) of death with 95% confidence intervals (CIs) were estimated using a Fine-Gray model.
DII scores were not significantly associated with all-cause mortality of PCa patients (HR=1.20; 95% CI: 0.82-1.76). However, considerable heterogeneity emerged according to Gleason score (p <0.01): no associations emerged among men with Gleason score 2-6 PCa; whereas, among patients with Gleason score 7-10 PCa, DII was directly associated with both all-cause and PCa-specific mortality (HR highest vs. lowest DII tertile: 2.88; 95% CI: 1.46-5.67; and 2.82; 95% CI: 1.17-6.80; respectively). Among patients with Gleason score 7-10 PCa, ten-year all-cause survival probabilities were 58% (95% CI: 47%-67%) for highest and 78% (95% CI: 67%-86%) for lowest DII tertile.
Study findings support the hypothesis that diet, through its inflammatory potential, may influence the prognosis of patients with more aggressive PCa. Dietary interventions aimed at decreasing inflammation may be considered to improve survival of men with PCa. This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/25w8QpV
via IFTTT
Fibroblast recruitment as a tool for ovarian cancer detection and targeted therapy
Abstract
Metastatic ovarian cancer, the most lethal of gynecologic malignancies, is typically managed by debulking surgery, followed by chemotherapy. However, despite significant efforts, survival rate remains low. We have previously demonstrated, in mouse models, a specific systemic homing of labeled fibroblasts to solid ovarian tumors. Here, we demonstrate the feasibility of utilizing this specific homing of genetically modified fibroblasts for detection and targeted therapy of orthotopic metastatic ovarian carcinoma model in immune-deficient mice. Using an in-vivo metastatic mouse model for ovarian cancer, we demonstrated that fibroblasts expressing fluorescent reporters injected intra-peritoneally, were specifically recruited to peritoneal tumor nodules (resulting in 93-100% co-localization). We further used fibroblasts over expressing the soluble receptor variant of VEGFR1 (s-Flt1). Mice bearing tumors were injected weekly with either control or s-Flt1 expressing fibroblasts. Injection of s-Flt1 expressing fibroblasts resulted in a significant reduction in the ascites volume, reduced vascularization of adherent metastases, and improved overall survival. Using fluorescently labeled fibroblasts for tumor detection with readily available intra-operative fluorescence imaging tools may be useful for tumor staging and directing biopsies or surgical efforts during exploratory or debulking surgery. Fibroblasts may serve as a beacon pointing to the otherwise invisible metastases in the peritoneal cavity of ovarian cancer patients. Utilizing the recruited fibroblasts also for targeted delivery of anti angiogenic or anti tumor molecules may aid in controlling tumor progression. Thus, these results suggest a novel approach for targeting ovarian tumor metastases for both tumor detection and therapy. This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/25xRIDI
via IFTTT
Δευτέρα 30 Μαΐου 2016
Weighted gene co-expression network analysis reveals key genes involved in pancreatic ductal adenocarcinoma development
Abstract
Purpose
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Up till now, the patient's prognosis remains poor which, among others, is due to the paucity of reliable early diagnostic biomarkers. In the past, candidate diagnostic biomarkers and therapeutic targets have been delineated from genes that were found to be differentially expressed in normal versus tumour samples. Recently, new systems biology approaches have been developed to analyse gene expression data, which may yield new biomarkers. As of yet, the weighted gene co-expression network analysis (WGCNA) tool has not been applied to PDAC microarray-based gene expression data.
Methods
PDAC microarray-based gene expression datasets, listed in the Gene Expression Omnibus (GEO) database, were analysed. After pre-processing of the data, we built two final datasets, Normal and PDAC, encompassing 104 and 129 patient samples, respectively. Next, we constructed a weighted gene co-expression network and identified modules of co-expressed genes distinguishing normal from disease conditions. Functional annotations of the genes in these modules were carried out to highlight PDAC-associated molecular pathways and common regulatory mechanisms. Finally, overall survival analyses were carried out to assess the suitability of the genes identified as prognostic biomarkers.
Results
Using WGCNA, we identified several key genes that may play important roles in PDAC. These genes are mainly related to either endoplasmic reticulum, mitochondrion or membrane functions, exhibit transferase or hydrolase activities and are involved in biological processes such as lipid metabolism or transmembrane transport. As a validation of the applied method, we found that some of the identified key genes (CEACAM1, MCU, VDAC1, CYCS, C15ORF52, TMEM51, LARP1 and ERLIN2) have previously been reported by others as potential PDAC biomarkers. Using overall survival analyses, we found that several of the newly identified genes may serve as biomarkers to stratify PDAC patients into low- and high-risk groups.
Conclusions
Using this new systems biology approach, we identified several genes that appear to be critical to PDAC development. As such, they may represent potential diagnostic biomarkers as well as therapeutic targets with clinical utility.
from Cancer via ola Kala on Inoreader http://ift.tt/25unG0n
via IFTTT
Genomic Characterization of High-Grade Serous Ovarian Cancer: Dissecting Its Molecular Heterogeneity as a Road Towards Effective Therapeutic Strategies
Abstract
High-grade serous ovarian carcinoma (HGSOC) accounts for the majority of the ovarian cancer deaths, but over the last years little improvement in overall survival has been achieved. HGSOC is a molecularly and clinically heterogeneous disease. At genomic level, it represents a C-class malignancy having frequent gene losses (NF1, RB1, PTEN) and gains (CCNE1, MYC). HGSOC shows a simple mutational profile with TP53 nearly always mutated and with other genes mutated at low frequency. Importantly, 50 % of all HGSOCs have genetic features indicating a homologous recombination (HR) deficiency. HR deficient tumors are highly sensitive to PARP inhibitor anticancer agents, which exhibit synthetic lethality with a defective HR pathway. Transcriptionally, HGSOCs can be grouped into different molecular subtypes with distinct biology and prognosis. Molecular stratification of HGSOC based on these genomic features may result in improved therapeutic strategies.
from Cancer via ola Kala on Inoreader http://ift.tt/25uFcRU
via IFTTT
Anomalous origin of the left coronary artery from the pulmonary artery in children: diagnostic use of multidetector computed tomography
Abstract
Background
Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital anomaly. It is important to demonstrate the anomalous origin of the left coronary artery and its course before surgery.
Objective
To explore the clinical diagnostic use of multidetector CT coronary angiography in detecting anomalous origin of the left coronary artery from the pulmonary artery in children.
Materials and methods
Nine children (2 boys, 7 girls) ages 2 months to 9 years with surgically confirmed anomalous origin of the left coronary artery from the pulmonary artery were studied. Clinical data, transthoracic echocardiography and CT coronary angiography images were retrospectively analyzed.
Results
Transthoracic echocardiography correctly diagnosed anomalous origin of the left coronary artery from the pulmonary artery in 7 of 9 patients (95% CI: 40–97%). CT coronary angiography revealed the anomalous origin of the left coronary artery in all children (95% CI: 66–100%). In a 4-year-old girl and a 9-year-old girl, CT coronary angiography showed dilation of the right coronary artery and collateral circulation between the right and the left coronary arteries.
Conclusion
CT coronary angiography is a useful method to show the anomalous origin of the coronary artery in children with anomalous origin of the left coronary artery from the pulmonary artery, especially for patients in whom origin of the left coronary artery cannot be detected by transthoracic echocardiography.
from Cancer via ola Kala on Inoreader http://ift.tt/1WUTvO4
via IFTTT
Weighted gene co-expression network analysis reveals key genes involved in pancreatic ductal adenocarcinoma development
Abstract
Purpose
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Up till now, the patient's prognosis remains poor which, among others, is due to the paucity of reliable early diagnostic biomarkers. In the past, candidate diagnostic biomarkers and therapeutic targets have been delineated from genes that were found to be differentially expressed in normal versus tumour samples. Recently, new systems biology approaches have been developed to analyse gene expression data, which may yield new biomarkers. As of yet, the weighted gene co-expression network analysis (WGCNA) tool has not been applied to PDAC microarray-based gene expression data.
Methods
PDAC microarray-based gene expression datasets, listed in the Gene Expression Omnibus (GEO) database, were analysed. After pre-processing of the data, we built two final datasets, Normal and PDAC, encompassing 104 and 129 patient samples, respectively. Next, we constructed a weighted gene co-expression network and identified modules of co-expressed genes distinguishing normal from disease conditions. Functional annotations of the genes in these modules were carried out to highlight PDAC-associated molecular pathways and common regulatory mechanisms. Finally, overall survival analyses were carried out to assess the suitability of the genes identified as prognostic biomarkers.
Results
Using WGCNA, we identified several key genes that may play important roles in PDAC. These genes are mainly related to either endoplasmic reticulum, mitochondrion or membrane functions, exhibit transferase or hydrolase activities and are involved in biological processes such as lipid metabolism or transmembrane transport. As a validation of the applied method, we found that some of the identified key genes (CEACAM1, MCU, VDAC1, CYCS, C15ORF52, TMEM51, LARP1 and ERLIN2) have previously been reported by others as potential PDAC biomarkers. Using overall survival analyses, we found that several of the newly identified genes may serve as biomarkers to stratify PDAC patients into low- and high-risk groups.
Conclusions
Using this new systems biology approach, we identified several genes that appear to be critical to PDAC development. As such, they may represent potential diagnostic biomarkers as well as therapeutic targets with clinical utility.
from Cancer via ola Kala on Inoreader http://ift.tt/25unG0n
via IFTTT
Prevalence of Germline Mutations in the Spindle Assembly Checkpoint Gene BUB1B in Individuals with Early-Onset Colorectal Cancer
ABSTRACT
Germline mutations in BUB1B, encoding BUBR1, one of the crucial components of the spindle assembly checkpoint (SAC), have been shown to cause variable phenotypes, including the recessive mosaic variegated aneuploidy (MVA) syndrome, which predisposes to cancer. Reduced levels of the wild-type BUBR1 protein have been linked to the development of gastrointestinal neoplasms. To determine whether mutations in BUB1B are enriched in individuals with colorectal cancer (CRC), we performed amplicon-based targeted next-generation sequencing of BUB1B on germline DNA of 192 individuals with early-onset CRC (≤50 years). None of the individuals was found to be homozygous or compound heterozygous for mutations in BUB1B. However, we did identify two rare heterozygous variants, p.Glu390del and p.Cys945Tyr, in patients who developed CRC at the ages of 41 and 43 years, respectively. Both variants were shown not to affect BUBR1 protein expression levels and protein localization. Since the p.Glu390del variant is located in the BUB3-binding domain, we also performed immunoprecipitation to examine whether this variant affects the binding of BUB1 or BUB3 to BUBR1 but, compared to wild-type BUBR1, no difference was observed. Our data suggest that mutations in BUB1B do not occur frequently in the germline of individuals with CRC and that BUB1B unlikely plays a major role in the predisposition to early-onset CRC. Whether carriers of pathogenic BUB1B mutations, such as the parents of MVA syndrome patients, have an increased risk for cancer remains of interest, as studies in mice have suggested that haploinsufficiency of BUB1B may cause an increase in carcinogen-induced tumours. This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/1sXfCHQ
via IFTTT
Modeling the Efficacy of the Extent of Surgical Resection in the Setting of Radiation Therapy for GBM
Summary
Standard therapy for GBM includes maximal surgical resection and radiation therapy. While it is established that radiation therapy provides the greatest survival benefit of standard treatment modalities, the impact of the extent of surgical resection (EOR) on patient outcome remains highly controversial. While some studies describe no correlation between EOR and patient survival even up to total resection, others propose either qualitative (partial vs subtotal vs complete resection) or quantitative EOR thresholds, below which there is no correlation with survival. This work uses a mathematical model in the form of a reaction-diffusion partial differential equation to simulate tumor growth and treatment with radiation therapy and surgical resection based on tumor-specific rates of diffusion and proliferation. Simulation of 36 tumors across a wide spectrum of diffusion and proliferation rates suggests that while partial or subtotal resections generally do not provide a survival advantage, complete resection significantly improves patient outcomes. Furthermore, our model predicts a tumor-specific quantitative threshold below which EOR has no effect on patient survival and demonstrates that this threshold increases with tumor aggressiveness, particularly with the rate of proliferation. Thus, this model may serve as an aid for determining both when surgical resection is indicated as well as the surgical margins necessary to provide clinically significant improvements in patient survival. Additionally, by assigning relative benefits to radiation and surgical resection based on tumor invasiveness and proliferation, this model confirms that (with the exception of the least aggressive tumors) the survival benefit of radiation therapy exceeds that of surgical resection.
This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/25tRVV7
via IFTTT
Sensitivities to various EGFR-TKIs of uncommon EGFR mutations L861Q and S768I: what is the optimal EGFR-TKI?
Summary
Most patients with non-small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations, such as deletions in exon 19 or the L858R mutation in exon 21, respond dramatically to EGFR tyrosine kinase inhibitors (EGFR-TKIs), and their sensitivities to various EGFR-TKIs have been well characterized. Our previous article showed the in vitro sensitivities of EGFR exon 18 mutations to EGFR-TKIs, but little information regarding the sensitivities of other uncommon EGFR mutations is available. First, stable transfectant Ba/F3 cell lines harboring EGFR L858R (Ba/F3-L858R), L861Q (Ba/F3-L861Q) or S768I (Ba/F3-S768I) mutations were created and their drug sensitivities to various EGFR-TKIs were examined. Both the Ba/F3-L861Q and Ba/F3-S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3-L858R cell line, but their sensitivities to afatinib were similar to that of the Ba/F3-L858R cell line. The Ba/F3-L861Q cell line was similarly sensitive and the Ba/F3-S768I cell line was less sensitive to osimertinib, compared with the Ba/F3-L858R cell line. The results of western blot analyses were consistent with these sensitivities. Next, similar experiments were also performed using the KYSE270 (L861Q) and KYSE 450 (S768I) cell lines, and their results were compatible with those of the transfectant Ba/F3 cell lines. Our findings suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib and that NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib. Overall, afatinib might be the optimal EGFR-TKI against these uncommon EGFR mutations.
This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/1Pcsgw5
via IFTTT
Regulation of H-Ras-driven MAPK signaling, transformation and tumorigenesis, but not PI3K signaling and tumor progression, by plasma membrane microdomains
Regulation of H-Ras-driven MAPK signaling, transformation and tumorigenesis, but not PI3K signaling and tumor progression, by plasma membrane microdomains
Oncogenesis 5, e228 (May 2016). doi:10.1038/oncsis.2016.36
Authors: J V Michael, J G T Wurtzel & L E Goldfinger
from Cancer via ola Kala on Inoreader http://ift.tt/1TRrAez
via IFTTT
Dietary fat overcomes the protective activity of thrombospondin-1 signaling in the ApcMin/+ model of colon cancer
Dietary fat overcomes the protective activity of thrombospondin-1 signaling in the ApcMin/+ model of colon cancer
Oncogenesis 5, e230 (May 2016). doi:10.1038/oncsis.2016.37
Authors: D R Soto-Pantoja, J M Sipes, G Martin-Manso, B Westwood, N L Morris, A Ghosh, N J Emenaker & D D Roberts
from Cancer via ola Kala on Inoreader http://ift.tt/25wcX98
via IFTTT
An ANCCA/PRO2000-miR-520a-E2F2 regulatory loop as a driving force for the development of hepatocellular carcinoma
An ANCCA/PRO2000-miR-520a-E2F2 regulatory loop as a driving force for the development of hepatocellular carcinoma
Oncogenesis 5, e229 (May 2016). doi:10.1038/oncsis.2016.22
Authors: J Huang, J Yang, Y Lei, H Gao, T Wei, L Luo, F Zhang, H Chen, Q Zeng & L Guo
from Cancer via ola Kala on Inoreader http://ift.tt/1TRqO0Z
via IFTTT
PTEN negatively regulates mTORC2 formation and signaling in grade IV glioma via Rictor hyperphosphorylation at Thr1135 and direct the mode of action of an mTORC1/2 inhibitor
PTEN negatively regulates mTORC2 formation and signaling in grade IV glioma via Rictor hyperphosphorylation at Thr1135 and direct the mode of action of an mTORC1/2 inhibitor
Oncogenesis 5, e227 (May 2016). doi:10.1038/oncsis.2016.34
Authors: K Bhattacharya, S Maiti & C Mandal
from Cancer via ola Kala on Inoreader http://ift.tt/25wcWSC
via IFTTT
Migration and invasion is inhibited by silencing ROR1 and ROR2 in chemoresistant ovarian cancer
Migration and invasion is inhibited by silencing ROR1 and ROR2 in chemoresistant ovarian cancer
Oncogenesis 5, e226 (May 2016). doi:10.1038/oncsis.2016.32
Authors: C E Henry, E Llamosas, A Djordjevic, N F Hacker & C E Ford
from Cancer via ola Kala on Inoreader http://ift.tt/1TRqTlf
via IFTTT
Cancer negatively impacts on sexual function in adolescents and young adults: The Aya Hope study
Abstract
Objective
This cohort study examined the impact of cancer on sexual function and intimate relationships in adolescents and young adults (AYAs). We also explored factors predicting an increased likelihood that cancer had negatively affected these outcomes.
Methods
Participants (n = 465, ages 15-39) in the Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE) study completed two surveys approximately 1 and 2 years post cancer diagnosis. We used multivariable logistic regression to determine factors negatively affected by perceptions of sexual function at 2 years post-diagnosis.
Results
Forty-nine percent of AYAs reported negative effects on sexual function at one year post cancer diagnosis and 70% of those persisted in their negative perceptions two years after diagnosis. Those reporting a negative impact at two years were more likely to be 25 years or older (OR, 2.53; 95% CI, 1.44-4.42), currently not raising children (OR, 1.81; 95% CI, 1.06-3.08), experiencing fatigue (OR, .99; 95% CI, .975-.998) and more likely to report that their diagnosis has had a negative effect on physical appearance (OR, 3.08; 95% CI, 1.97-4.81). Clinical factors and mental health were not significant predictors of negative effects on sexual function.
Conclusions
Many AYAs diagnosed with cancer experience a persistent negative impact on sexual life up to two years following diagnosis. The findings underscore the need to develop routine protocols to assess sexual function in AYAs with cancer and to provide comprehensive management in the clinical setting. This article is protected by copyright. All rights reserved.
from Cancer via ola Kala on Inoreader http://ift.tt/1U7CEl2
via IFTTT
Initial Testing (Stage 1) of MK-8242—A Novel MDM2 Inhibitor—by the Pediatric Preclinical Testing Program
Background
MK-8242 is an inhibitor of MDM2 that stabilizes the tumor suppressor TP53 and induces growth arrest or apoptosis downstream of TP53 induction.
Procedures
MK-8242 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.0 nM to 10.0 μM and against the PPTP in vivo xenograft panels using oral gavage on Days 1–5 and Day 15–19 at a dose of 125 mg/kg (solid tumors) or 75 mg/kg (acute lymphoblastic leukemia [ALL] models).
Results
The median IC50 for MK-8242 was 0.07 μM for TP53 wild-type cell lines versus >10 μM for TP53 mutant cell lines. MK-8242 induced a twofold or greater delay in time to event in 10 of 17 (59%) of TP53 wild-type solid tumor xenografts, excluding osteosarcoma xenografts that have very low TP53 expression. Objective responses were observed in seven solid tumor xenografts representing multiple histotypes. For the systemic-disease ALL panel, among eight xenografts there were two complete responses (CRs) and six partial responses (PRs). Two additional MLL-rearranged xenografts (MV4;11 and RS4;11) grown subcutaneously showed maintained CR and PR, respectively. The expected pharmacodynamic responses to TP53 activation were observed in TP53 wild-type models treated with MK-8242. Pharmacokinetic analysis showed that MK-8242 drug exposure in SCID mice appears to exceed that was observed in adult phase 1 trials.
Conclusions
MK-8242-induced tumor regressions across multiple solid tumor histotypes and induced CRs or PRs for most ALL xenografts. This activity was observed at MK-8242 drug exposures that appear to exceed those observed in human phase 1 trials.
from Cancer via ola Kala on Inoreader http://ift.tt/1qWODKh
via IFTTT
Prevalence of Helicobacter pylori Infection in Patients with Squamous Cell Carcinoma of the Oesophagus. A Descriptive Case Series Study
Abstract
Introduction
Helicobacter pylori is an important causative factor in gastric carcinogenesis; its role in extra-gastric gastrointestinal malignancies such as oesophageal cancer is controversial. H. pylori is thought to cause extensive gastric atrophy associated with squamous cell carcinoma of the oesophagus. We conducted a study to determine the prevalence of H. pylori infection in patients with squamous cell carcinoma of the oesophagus.
Method
We collected biopsies from the antrum and corpus of 59 patients with confirmed squamous cell carcinoma of the oesophagus, two from each area. These were then examined by an experienced histopathologist using methylene blue staining for the presence of H. pylori.
Results
H. pylori was found in 30 (51 %) of the patients, a prevalence similar to that of the general population in South Africa. Five patients were found to have associated intestinal metaplasia, and all but two had chronic inflammation.
Conclusion
The prevalence of H. pylori in our patients with squamous cell carcinoma of the oesophagus is 51 %, similar to that previously reported in the general population.
from Cancer via ola Kala on Inoreader http://ift.tt/1U76hmr
via IFTTT
Defining the optimal timing of adjuvant therapy for resected pancreatic adenocarcinoma: A statewide cancer registry analysis
Background
Long-term results of the ESPAC-3 trial suggest that while completing adjuvant therapy (AT) is necessary after resection of pancreatic ductal adenocarcinoma (PDAC), early initiation (within 8 weeks) may not be associated with improved overall survival (OS). The primary aim of this study was to evaluate the OS impact of early versus late AT in a statewide analysis.
Methods
Patients with stages I–III PDAC in the Kentucky Cancer Registry (KCR) from 2004 to 2013, were evaluated. Those undergoing pancreatectomy were stratified into two groups ("early," <8 weeks, vs. "late," 8–16 weeks).
Results
Of 2,221 diagnosed patients with stages I–III, 831 (37.4%) underwent pancreatectomy upfront. Of these, only 420 (50.5%) received AT. Initiation date of AT was not associated with OS (median OS: early, 20.2 vs. late, 19.0 months, P = 0.97). On multivariate analysis, factors that affected OS included stage (II, HR-1.82, P = 0.017; III, HR-3.77, P < 0.001), node positivity (HR-1.51, P = 0.004), poorly/undifferentiated grade (HR-1.34; P = 0.011), but not AT initiation date.
Conclusions
In this statewide analysis, there was no difference in OS between early and late AT initiation for resected PDAC. The ideal window for AT initiation remains unknown as tumor biology continues to trump regimens from the past decade. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
from Cancer via ola Kala on Inoreader http://ift.tt/1sWFKm8
via IFTTT
Intralesional PV-10 for in-transit melanoma—A single-center experience
Background and Objectives
Patients with in-transit melanoma metastasis have longer median survival than patients with distant metastatic disease. Furthermore, local disease control is an important endpoint for symptom management. The treatment of unresectable loco-regional recurrence or in-transit disease has been historically managed with a combination of treatments including surgery, radiotherapy, isolated limb infusion or perfusion as well as systemic therapies. Intralesional PV-10 has been used at Peter MacCallum Cancer Centre since 2010, and the current report presents a retrospective analysis of patient outcomes, reporting the response rates, durability of responses, and observed toxicities.
Methods
Records were analyzed retrieving details of 19 patients treated with PV-10 over a 4-year period from 2010 to 2014. Medical records were reviewed for these patients and data extracted.
Results
Nineteen patients with in-transit melanoma were treated with intralesional PV-10 between 2010 and 2014. Disease control (complete or partial response or disease stability) was achieved in 68% of patients with 26% having a complete response. This was achieved with minimal associated toxicity.
Conclusions
PV-10 is an effective, durable, well-tolerated treatment tool with an acceptable side effect profile for the management of unresectable in-transit melanoma. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
from Cancer via ola Kala on Inoreader http://ift.tt/1UnNqpX
via IFTTT
Patterns of major wound complications following multidisciplinary therapy for lower extremity soft tissue sarcoma
Background and Objectives
The purpose of this study was to determine the pattern and timing of major wound complications (MWCs) in patients at our institution who received multimodality treatment for lower extremity soft tissue sarcoma (LE-STS) and to evaluate the impact of MWCs on tumor control and patient outcomes.
Methods
The medical records of 102 LE-STS patients treated with limb-sparing surgery and radiation therapy were reviewed. MWCs were defined as secondary operations with anesthesia, seroma/hematoma aspiration, admission for IV antibiotics, or persistent deep packing.
Results
MWCs occurred in 22% of patients, with 45% of events occurring >120 days after resection. On multivariate analysis, preoperative external beam radiation therapy (EBRT) (OR 4.29, 95% CI 1.06–17.40, P = 0.042) and skin graft placement (OR 6.39, 95% CI 1.37–29.84, P = 0.018) were found to be independent predictors of MWCs. MWC occurrence did not predict for chronic toxicity and did not impact tumor control or survival.
Conclusions
A considerable proportion of MWCs occur >120 days from surgical resection with preoperative EBRT and skin graft placement independent predictors for MWCs. While an additional source of morbidity, MWC occurrence did not impact tumor control, nor did it predict for chronic toxicity. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
from Cancer via ola Kala on Inoreader http://ift.tt/1sWFK5p
via IFTTT
Κυριακή 29 Μαΐου 2016
Re-irradiation of prostate cancer local failures after previous curative radiotherapy: long-term outcome and tolerance
Publication date: Available online 28 May 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Thomas Zilli, Eileen Benz, Giovanna Dipasquale, Michel Rouzaud, Raymond Miralbell
Purpose/ObjectiveTo evaluate safety, feasibility, side-effect profile, and proof of concept of external beam radiotherapy (EBRT) with or without a brachytherapy (BT) boost for salvage of exclusive local failure after primary EBRT for prostate cancer.Materials and MethodsFourteen patients with presumed exclusive local recurrence after primary EBRT with or without BT were considered eligible for re-irradiation. The median normalized total dose in 2 Gy-fractions (NTD2Gy, α/β ratio=1.5 Gy) was 74 Gy (66-98.4) at 1st irradiation. Median time between the 1st RT and the re-irradiation was 6.1 years (range, 4.7-10.2).ResultsBetween 2003 and 2008 salvage treatment was delivered with a median NTD2Gy of 85.1 Gy (70-93.4) to the prostate with EBRT with (n=10) or without (n=4) BT. Androgen deprivation was given to 12 patients (median time of 12 months). No Grade ≥ 3 toxicity was observed during and within 6 weeks after RT. After a median follow-up of 94 months (range, 48-172) post-salvage RT, 5-year Grade ≥3 GU and GI toxicity-free survival figures were 77.9±11.3% and 57.1±13.2%, respectively. Four patients presented with combined Grade 4 GU/GI toxicity. The 5-year biochemical relapse-free, local relapse-free, distant metastasis-free and cancer-specific survivals were 35.7±12.8%, 50.0±13.4%, 85.7±9.4%, and 100%, respectively.ConclusionSalvage whole gland re-irradiation for patients with a suspicious of exclusive local recurrence after initial RT may be associated with a high rate of severe radiation-induced side-effects and a poor long-term biochemical and local control.
Teaser
In this retrospective study we evaluated the long-term results of fourteen prostate cancer patients treated with salvage external beam radiotherapy (EBRT) for exclusive local failure after primary EBRT. Whole gland re-irradiation resulted in a high rate of severe radiation-induced side-effects and a poor long-term biochemical and local control. Alternative salvage re-irradiation modalities should be explored for selected cases of local relapse in accurately designed prospective trials.from Cancer via ola Kala on Inoreader http://ift.tt/25tPpSj
via IFTTT
Prognostic value of p16 status on the development of a complete response in involved oropharynx cancer neck nodes after cisplatin based chemoradiation – a secondary analysis of NRG Oncology RTOG 0129
Publication date: Available online 28 May 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Thomas J. Galloway, Qiang (Ed) Zhang, Phuc Felix Nguyen-Tan, David I. Rosenthal, Denis Soulieres, André Fortin, Craig L. Silverman, Megan E. Daly, John A. Ridge, J Alexander Hammond, Quynh-Thu Le
PurposeTo determine the relationship between p16 status and the regional response of patients with node positive oropharynx cancer treated on Study XXXX.Materials and MethodsPatients with N1-N3 oropharynx cancer and known p16 status who underwent treatment on Study XXXX were analyzed. Pathologic complete response rates in patients treated with a post-chemoradiation neck dissection (with p16-positive or p16-negative cancer) were compared by Fisher's exact test. Patients managed expectantly were compared to those treated with a neck dissection.ResultsNinety-nine of 292 (34%) of patients with node positive oropharynx cancer and known p16 status underwent a post-treatment neck dissection (p16-positive: n=69 and p16-negative: n=30). The remaining 193 patients with malignant lymphadenopathy at diagnosis were observed. Neck dissection was performed a median of 70 (range 17 - 169) days after completion of chemoradiation. Neither the pre-treatment nodal stage (p=0.71) nor the post-radiation, pre-neck dissection clinical/radiographic neck assessment (p=0.42) differed by p16 status.A pathologic complete response (pCR) was more common among p16-positive patients (78%) than p16-negative patients (53%, p=0.02) and was associated with a reduced incidence of local-regional failure (HR 0.33, p = 0.003). On multivariate analysis (MVA) of local-regional failure a test for interaction between pCR and p16 status was not significant (p = 0.37).One-hundred-ninety-three of 292 (66%) of initially node positive patients were managed without a post-treatment neck dissection. Development of a clinical CR was not significantly influenced by p16-status (p = 0.42). Observed patients with a clinical nodal CR had disease control outcomes similar to patients with a pCR neck dissection.ConclusionsPatients with p16-positive tumors had significantly higher complete pathologic response and locoregional control rates than those with p16-negative tumors.
Teaser
This second analysis of XXXX investigates the role of post-treatment neck dissection in the management of node positive oropharynx cancer managed with primary chemoradiation. Patients treated on protocol were imaged 6-8 weeks after the completion of chemoradiation and post-treatment neck dissection was recommended for those with advanced stage (N2-N3) at diagnosis. p16-positive tumors are significantly more likely to develop a complete pathologic response. Many patients were ultimately observed, without increased regional failure.from Cancer via ola Kala on Inoreader http://ift.tt/1UcJ3eq
via IFTTT
Σάββατο 28 Μαΐου 2016
Prognostic value of preoperative von Willebrand factor plasma levels in patients with Glioblastoma
Abstract
Circulating biomarker for malignant gliomas could improve both differential diagnosis and clinical management of brain tumor patients. Among all gliomas, glioblastoma (GBM) is considered the most hypervascularized tumor with activation of multiple proangiogenic signaling pathways that enhance tumor growth. To investigate whether preoperative antigen plasma level of von Willebrand Factor (VWF:Ag) might be possible marker for GBM onset, progression, and prognosis, we retrospectively examined 57 patients with histological diagnosis for GBM and 23 meningiomas (MNGs), benign intracranial expansive lesions, enrolled as controls. Blood samples were collected from all the patients before tumor resection. Plasma von Willebrand Factor (VWF):Ag levels were determined by using a latex particle-enhanced immunoturbidimetric assay. The median levels of vWF:Ag were significantly higher in GBMs than in meningiomas (MNGs) (183 vs. 133 IU/dL, P = 0.01). The cumulative 1-year survival was significantly shorter in patients with VWF:Ag levels >200 IU/dL than in those with levels <200 IU/dL and increased VWF levels were associated with a threefold higher risk of death in GBM patients. Our data suggest that VWF:Ag could be a circulating biomarker of disease malignancy, that could be considered, in association with other genetic and epigenetic factors, currently available in the GBM management. Future studies should investigate whether plasma VWF:Ag levels could also be used to monitor therapeutic effects and whether it may have a prognostic value.
Circulating biomarker for malignant glioblastoma could improve both differential diagnosis and clinical management of brain tumor patients. Plasma von Willebrand Factor (VWF):Ag levels were determined in 80 patients (57 glioblastoma and 23 meningiomas). The median levels of vWF:Ag were significantly higher in glioblastoma (GBMs) than in meningiomas (MNGs) and the cumulative 1-year survival was significantly shorter in patients with VWF:Ag levels >200 IU/dL than in those with levels <200 IU/dL and increased VWF levels were associated with a threefold higher risk of death in GBM patients. Our data suggest that VWF:Ag could be a circulating biomarker of disease malignancy, that could be considered, in association with other genetic and epigenetic factors, currently available in the GBM management.
from Cancer via ola Kala on Inoreader http://ift.tt/1sF2OVB
via IFTTT
Acute hemolysis in a patient with a newly diagnosed glioblastoma
CNS Oncology Ahead of Print.
from Cancer via ola Kala on Inoreader http://ift.tt/1WSz7wM
via IFTTT
Anaplastic astrocytoma
CNS Oncology Ahead of Print.
from Cancer via ola Kala on Inoreader http://ift.tt/1U47FpU
via IFTTT
Sox2: regulation of expression and contribution to brain tumors
CNS Oncology Ahead of Print.
from Cancer via ola Kala on Inoreader http://ift.tt/1WSzaJ0
via IFTTT
Our panel of experts highlights the most important research articles across the spectrum of topics relevant to the field of CNS oncology
CNS Oncology Ahead of Print.
from Cancer via ola Kala on Inoreader http://ift.tt/1U473ke
via IFTTT
A selected review of abstracts from the 20th Annual Meeting of the Society for Neuro-Oncology (SNO)
CNS Oncology Ahead of Print.
from Cancer via ola Kala on Inoreader http://ift.tt/1WSyu6x
via IFTTT
Disulfiram/Copper Enhance Temozolomide Treatment for Glioblastoma
Purpose: Glioblastoma is one of the most lethal cancers in humans, and with existing therapy, survival remains at 14.6 months. Current barriers to successful treatment include their infiltrative behavior, extensive tumor heterogeneity, and the presence of a stem-like population of cells, termed brain tumor–initiating cells (BTIC) that confer resistance to conventional therapies.
Experimental Design: To develop therapeutic strategies that target BTICs, we focused on a repurposing approach that explored already-marketed (clinically approved) drugs for therapeutic potential against patient-derived BTICs that encompass the genetic and phenotypic heterogeneity of glioblastoma observed clinically.
Results: Using a high-throughput in vitro drug screen, we found that montelukast, clioquinol, and disulfiram (DSF) were cytotoxic against a large panel of patient-derived BTICs. Of these compounds, disulfiram, an off-patent drug previously used to treat alcoholism, in the presence of a copper supplement, showed low nanomolar efficacy in BTICs including those resistant to temozolomide and the highly infiltrative quiescent stem-like population. Low dose DSF-Cu significantly augmented temozolomide activity in vitro, and importantly, prolonged in vivo survival in patient-derived BTIC models established from both newly diagnosed and recurrent tumors. Moreover, we found that in addition to acting as a potent proteasome inhibitor, DSF-Cu functionally impairs DNA repair pathways and enhances the effects of DNA alkylating agents and radiation. These observations suggest that DSF-Cu inhibits proteasome activity and augments the therapeutic effects of DNA-damaging agents (temozolomide and radiation).
Conclusions: DSF-Cu should be considered as an adjuvant therapy for the treatment of patients with glioblastoma in both newly diagnosed and recurrent settings. Clin Cancer Res; 1–16. ©2016 AACR.
from Cancer via ola Kala on Inoreader http://ift.tt/1Uc7MPX
via IFTTT
Εγγραφή σε:
Αναρτήσεις (Atom)