Submucous uterine adenosarcoma—minimally invasive treatment

Abstract

Background

Uterine adenosarcomas are rare malignant gynaecological tumours. Due to its submucous localization, they can be easily confound with benign tumours like endometrial polyps or submucous myomas. However, the treatment of uterine adenosarcomas requires an oncologic surgical approach.

Case presentation

In the following case report, we present the minimally invasive treatment of a uterine adenosarcoma by hysteroscopy and laparoscopy in a 37-year-old patient and discuss the special role of hysteroscopy in such cases.

Conclusions

In case of unknown or suspect intrauterine tumours, a diagnostic and operative hysteroscopy with biopsy could be realized prior to laparoscopic hysterectomy especially when the use of a laparoscopic electric morcellation is planned. Thus, a correct oncologic approach can be guaranteed if an adenosarcoma is diagnosed.

Trial registration

ISRCTN

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Comparative effectiveness of radiotherapy with vs. without temozolomide in older patients with glioblastoma

Abstract

It is unknown whether the addition of temozolomide (TMZ) to radiotherapy (RT) is associated with improved overall survival (OS) among older glioblastoma patients. We performed a retrospective cohort SEER-Medicare analysis of 1652 patients aged ≥65 years with glioblastoma who received ≥10 fractions of RT from 2005 to 2009, or from 1995 to 1999 before TMZ was available. Three cohorts were assembled based on diagnosis year and treatment initiated within 60 days of diagnosis: (1) 2005–2009 and TMZ/RT, (2) 2005–2009 and RT only, or (3) 1995–1999 and RT only. Associations with OS were estimated using Cox proportional hazards models and propensity score analyses; OS was calculated starting 60 days after diagnosis. Pre-specified sensitivity analyses were performed among patients who received long-course RT (≥27 fractions). Median survival estimates were 7.4 (IQR, 3.3–14.7) months for TMZ/RT, 5.9 (IQR, 2.6–12.1) months for RT alone in 2005–2009, and 5.6 (IQR, 2.7–9.6) months for RT alone in 1995–1999. OS at 2 years was 10.1 % for TMZ/RT, 7.1 % for RT in 2005–2009, and 4.7 % for RT in 1995–1999. Adjusted models suggested decreased mortality risk for TMZ/RT compared to RT in 2005–2009 (AHR, 0.86; 95 % CI, 0.76–0.98) and RT in 1995–1999 (AHR, 0.71; 95 % CI, 0.57–0.90). Among patients from 2005 to 2009 who received long-course RT, however, the addition of TMZ did not significantly improve survival (AHR, 0.91; 95 % CI, 0.80–1.04). In summary, among a large cohort of older glioblastoma patients treated in a real-world setting, the addition of TMZ to RT was associated with a small survival gain.

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Pharmacokinetic and pharmacodynamic study of doxorubicin in children with cancer: results of a “European Pediatric Oncology Off-patents Medicines Consortium” trial

Abstract

Purpose

Doxorubicin is a key component in many pediatric oncology treatment regimens; still pharmacology data on which current dosing regimens are based are very limited.

Methods

We conducted a multinational pharmacokinetic study investigating age dependency of doxorubicin metabolism and elimination in children with cancer. One hundred and one patients treated with doxorubicin according to a cancer-specific national or European therapeutic trial were recruited. Doses of doxorubicin ranged from 10.4 to 57.7 mg/m². Blood samples for measurement of doxorubicin and its metabolite doxorubicinol were collected after two administrations, with five samples collected in children <3 years and eight in children ≥3 years. A population pharmacokinetic approach was used for analysis, including pharmacogenetic covariates. Natriuretic peptides and cardiac troponins were measured to evaluate their role as early indicators of cardiotoxicity.

Results

Age dependence of doxorubicin clearance was demonstrated, with children less than 3 years having a statistically significant lower clearance (21.1 ± 5.8 l/h/m²) than older children (26.6 ± 6.7 l/h/m²) (p = 0.0004) after correcting for body surface area. No effect of the investigated genetic polymorphisms on the pharmacokinetics could be observed. Although natriuretic peptides were transiently elevated after each doxorubicin administration and troponin levels increased with increasing doxorubicin exposure, only limited correlation could be observed between their blood levels and doxorubicin pharmacokinetics.

Conclusion

In the European framework of funding and regulatory support, an add-on study to existing therapeutic trials was developed. The pediatric need concerning missing PK data could be addressed with limited burden for the patients. Empirically used dose adaptations for infants were generally found to be justified based on our PK analyses.

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EGFR mutation status of paired cerebrospinal fluid and plasma samples in EGFR mutant non-small cell lung cancer with leptomeningeal metastases

Abstract

Purpose

Central nervous system (CNS) is the prevalent site for metastases in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-relapsed NSCLC patients. To understand the EGFR mutation status in paired cerebrospinal fluid (CSF) and plasma samples after EGFR-TKI treatment failure might be useful to guide the treatment of intra- and extracranial tumors in those patients.

Methods

Paired CSF and plasma samples were collected from seven NSCLC patients with CNS metastases after EGFR-TKI failure. EGFR mutations were tested by amplification refractory mutation system (ARMS) and droplet digital PCR (ddPCR) methods. Gefitinib concentrations were evaluated by high-performance liquid chromatography–mass spectrometry (HPLC–MS/MS).

Results

EGFR mutations were detected in all seven CSF samples, including three of E19-Del, three of L858R and one of E19-Del&T790M by both methods. On the other hand, majority of the matched plasma samples (5/7) were negative for EGFR mutations by both methods. The other two plasma samples were positive for E19-Del&T790M by ddPCR, and one of them had undetectable T790M by ARMS. Gefitinib concentration in CSF was much lower than that in plasma (mean CSF/plasma ratio: 1.8 %).

Conclusions

After EGFR-TKI failure, majority of the NSCLC patients with CNS metastases remained positive detection of EGFR sensitive mutations in CSF, but much less detection in the matched plasma. Significantly low exposure of gefitinib in CSF might explain the intracranial protection of the EGFR sensitive mutation positive tumor cells.

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Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease

Abstract

Extracellular vesicles (EVs) play key roles in glioblastoma (GBM) biology and represent novel sources of biomarkers that are detectable in the peripheral circulation. Despite this notionally non-invasive approach to assess GBM tumours in situ, a comprehensive GBM EV protein signature has not been described. Here, EVs secreted by six GBM cell lines were isolated and analysed by quantitative high-resolution mass spectrometry. Overall, 844 proteins were identified in the GBM EV proteome, of which 145 proteins were common to EVs secreted by all cell lines examined; included in the curated EV compendium (Vesiclepedia_559; http://ift.tt/WAcpwx). Levels of 14 EV proteins significantly correlated with cell invasion (invadopodia production; r² > 0.5, p < 0.05), including several proteins that interact with molecules responsible for regulating invadopodia formation. Invadopodia, actin-rich membrane protrusions with proteolytic activity, are associated with more aggressive disease and are sites of EV release. Gene levels corresponding to invasion-related EV proteins showed that five genes (annexin A1, actin-related protein 3, integrin-β1, insulin-like growth factor 2 receptor and programmed cell death 6-interacting protein) were significantly higher in GBM tumours compared to normal brain in silico, with common functions relating to actin polymerisation and endosomal sorting. We also show that Cavitron Ultrasonic Surgical Aspirator (CUSA) washings are a novel source of brain tumour-derived EVs, demonstrated by particle tracking analysis, TEM and proteome profiling. Quantitative proteomics corroborated the high levels of proposed invasion-related proteins in EVs enriched from a GBM compared to low-grade astrocytoma tumour. Large-scale clinical follow-up of putative biomarkers, particularly the proposed survival marker annexin A1, is warranted.

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Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease

Abstract

Extracellular vesicles (EVs) play key roles in glioblastoma (GBM) biology and represent novel sources of biomarkers that are detectable in the peripheral circulation. Despite this notionally non-invasive approach to assess GBM tumours in situ, a comprehensive GBM EV protein signature has not been described. Here, EVs secreted by six GBM cell lines were isolated and analysed by quantitative high-resolution mass spectrometry. Overall, 844 proteins were identified in the GBM EV proteome, of which 145 proteins were common to EVs secreted by all cell lines examined; included in the curated EV compendium (Vesiclepedia_559; http://ift.tt/WAcpwx). Levels of 14 EV proteins significantly correlated with cell invasion (invadopodia production; r² > 0.5, p < 0.05), including several proteins that interact with molecules responsible for regulating invadopodia formation. Invadopodia, actin-rich membrane protrusions with proteolytic activity, are associated with more aggressive disease and are sites of EV release. Gene levels corresponding to invasion-related EV proteins showed that five genes (annexin A1, actin-related protein 3, integrin-β1, insulin-like growth factor 2 receptor and programmed cell death 6-interacting protein) were significantly higher in GBM tumours compared to normal brain in silico, with common functions relating to actin polymerisation and endosomal sorting. We also show that Cavitron Ultrasonic Surgical Aspirator (CUSA) washings are a novel source of brain tumour-derived EVs, demonstrated by particle tracking analysis, TEM and proteome profiling. Quantitative proteomics corroborated the high levels of proposed invasion-related proteins in EVs enriched from a GBM compared to low-grade astrocytoma tumour. Large-scale clinical follow-up of putative biomarkers, particularly the proposed survival marker annexin A1, is warranted.

http://ift.tt/2eOMIXS

Up-regulation of small nucleolar RNA 78 is correlated with aggressive phenotype and poor prognosis of hepatocellular carcinoma

Abstract

Small nucleolar RNAs (snoRNAs) as a novel molecular species may have significant and comprehensive influences on the development and progression of hepatocellular carcinoma (HCC). We recently characterized snoRNA transcriptome signatures in HCC tissues by small RNA sequencing and found that small nucleolar RNA 78 (SNORD78) was associated with HCC. However, little is known about the pathological role of SNORD78 in HCC patients. This study aimed to profile SNORD78 expression signature and then to explore the pathogenesis of SNORD78 in HCC. The real-time PCR results showed that SNORD78 was greatly upregulated in HCC tissues than adjacent noncancerous tissues (p = 0.004). Correlation analysis showed that high-level expression of SNORD78 was notably associated with tumor number (single vs. multiply, p = 0.02), stage (I∼II vs. III∼IV, p = 0.014), and distant metastasis (absent vs. present, p = 0.01) in HCC patients. Univatiate and multivariate analyses showed that SNORD78 was a significant prognostic predictor for overall survival and recurrence-free survival of HCC patients (hazard ratio = 1.375, 95 % CI = 1.125–1.680, p = 0.002; hazard ratio = 1.418, 95 % CI = 1.201–1.675, p < 0.001). Moreover, Kaplan-Meier analysis showed that high-level expression of SNORD78 was associated with short overall survival and recurrence-free survival of HCC patients (p = 0.023, 0.014). Functionally, knockdown of SNORD78 significantly inhibited cellular proliferation, migration, and invasion of SK-Hep-1 via inducing G0/G1 cell cycle arrest and apoptosis. In conclusion, SNORD78 may be associated with aggressive phenotype and poor prognosis of HCC.

http://ift.tt/2eAUGA6

Up-regulation of small nucleolar RNA 78 is correlated with aggressive phenotype and poor prognosis of hepatocellular carcinoma

Abstract

Small nucleolar RNAs (snoRNAs) as a novel molecular species may have significant and comprehensive influences on the development and progression of hepatocellular carcinoma (HCC). We recently characterized snoRNA transcriptome signatures in HCC tissues by small RNA sequencing and found that small nucleolar RNA 78 (SNORD78) was associated with HCC. However, little is known about the pathological role of SNORD78 in HCC patients. This study aimed to profile SNORD78 expression signature and then to explore the pathogenesis of SNORD78 in HCC. The real-time PCR results showed that SNORD78 was greatly upregulated in HCC tissues than adjacent noncancerous tissues (p = 0.004). Correlation analysis showed that high-level expression of SNORD78 was notably associated with tumor number (single vs. multiply, p = 0.02), stage (I∼II vs. III∼IV, p = 0.014), and distant metastasis (absent vs. present, p = 0.01) in HCC patients. Univatiate and multivariate analyses showed that SNORD78 was a significant prognostic predictor for overall survival and recurrence-free survival of HCC patients (hazard ratio = 1.375, 95 % CI = 1.125–1.680, p = 0.002; hazard ratio = 1.418, 95 % CI = 1.201–1.675, p < 0.001). Moreover, Kaplan-Meier analysis showed that high-level expression of SNORD78 was associated with short overall survival and recurrence-free survival of HCC patients (p = 0.023, 0.014). Functionally, knockdown of SNORD78 significantly inhibited cellular proliferation, migration, and invasion of SK-Hep-1 via inducing G0/G1 cell cycle arrest and apoptosis. In conclusion, SNORD78 may be associated with aggressive phenotype and poor prognosis of HCC.

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Editorial (Thematic Issue: Pathogenetic Mechanisms of CLL - A Target in Therapy).

Editorial (Thematic Issue: Pathogenetic Mechanisms of CLL - A Target in Therapy).

Curr Cancer Drug Targets. 2016;16(8):651

Authors: Bozko M, Podhorecka M, Macheta A, Bozko A, Malek NP, Bozko P

PMID: 27758697 [PubMed - in process]

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The short-term outcomes of laparoscopic multivisceral resection for locally advanced colorectal cancer: our experience of 39 cases

Abstract

Purpose

Laparoscopic surgery for locally advanced colorectal cancer suspected of direct invasion to adjacent organs or structures remains controversial because of its high conversion rate, inadequate oncologic clearance and surgical outcomes. This study retrospectively evaluated the short-term outcomes of laparoscopic multivisceral resection for colorectal cancer and investigated the factors influencing conversion to open surgery.

Methods

Between 2010 and 2015, 39 patients who underwent laparoscopic multivisceral resection for colorectal cancer intraoperatively suspected of direct invasion to adjacent organs or structures were included. The conversion rate, resection margin status, surgical results, and morbidity and mortality rates were evaluated. We also investigated the factors influencing conversion.

Results

The conversion rate was 28 %. The resection margin was negative in all cases. The median operative time was 247 min, and the median blood loss was 80 ml. The postoperative mortality rate was 0 %, and the morbidity rate was 28 %; complications of Grade 3 or more were observed in 2 patients (5 %). The factors influencing conversion were ≥2 adherent organs (p = 0.028) and clinical suspicion of direct invasion to adjacent organs (cT4b) (p = 0.076).

Conclusion

Laparoscopic multivisceral resection for colorectal cancer intraoperatively suspected of direct invasion to adjacent organs or structures is feasible in selected patients. Conversion is more likely with ≥2 adherent organs and cT4b.

http://ift.tt/2ert5Rs

Current status of prophylactic surgical treatment for familial adenomatous polyposis in Japan

Abstract

Purpose

We conducted this study to clarify the current clinical practice of prophylactic colectomy for patients with familial adenomatous polyposis (FAP) in Japan.

Methods

This retrospective multi-center cohort study involved 23 specialized institutions for colorectal disease in Japan. We analyzed the records of 147 patients who underwent prophylactic surgical treatment between 2000 and 2012. Patients were divided into Group 1 (2000–2006) and Group 2 (2007–2012) based on their date of surgery.

Results

Age at the time of prophylactic surgery was 27 and 31 years in Groups 1 and 2, respectively. The proportion of attenuated FAP was significantly lower in Group 2 than in Group 1 (1.0 vs. 13 %, respectively). Pathological examination revealed an increased incidence of malignant polyps in the resected specimens from Group 2 patients (10 vs. 23 %, respectively; P = 0.034). Laparoscopic surgery was more frequent in Group 2 than in Group 1 (61 vs. 40 %, respectively). There was no surgical mortality in either group.

Conclusion

Prophylactic surgery for FAP results in good short-term surgical outcomes in Japan. The current surgical approach is characterized by limited surgical indications for patients with attenuated FAP, delayed timing of colectomy, and the increasing standardization of laparoscopic surgery.

http://ift.tt/2efDSmt

Issue Information - Ed Board

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Issue Information - TOC

http://ift.tt/2e7LjIA

The short-term outcomes of laparoscopic multivisceral resection for locally advanced colorectal cancer: our experience of 39 cases

Abstract

Purpose

Laparoscopic surgery for locally advanced colorectal cancer suspected of direct invasion to adjacent organs or structures remains controversial because of its high conversion rate, inadequate oncologic clearance and surgical outcomes. This study retrospectively evaluated the short-term outcomes of laparoscopic multivisceral resection for colorectal cancer and investigated the factors influencing conversion to open surgery.

Methods

Between 2010 and 2015, 39 patients who underwent laparoscopic multivisceral resection for colorectal cancer intraoperatively suspected of direct invasion to adjacent organs or structures were included. The conversion rate, resection margin status, surgical results, and morbidity and mortality rates were evaluated. We also investigated the factors influencing conversion.

Results

The conversion rate was 28 %. The resection margin was negative in all cases. The median operative time was 247 min, and the median blood loss was 80 ml. The postoperative mortality rate was 0 %, and the morbidity rate was 28 %; complications of Grade 3 or more were observed in 2 patients (5 %). The factors influencing conversion were ≥2 adherent organs (p = 0.028) and clinical suspicion of direct invasion to adjacent organs (cT4b) (p = 0.076).

Conclusion

Laparoscopic multivisceral resection for colorectal cancer intraoperatively suspected of direct invasion to adjacent organs or structures is feasible in selected patients. Conversion is more likely with ≥2 adherent organs and cT4b.

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Current status of prophylactic surgical treatment for familial adenomatous polyposis in Japan

Abstract

Purpose

We conducted this study to clarify the current clinical practice of prophylactic colectomy for patients with familial adenomatous polyposis (FAP) in Japan.

Methods

This retrospective multi-center cohort study involved 23 specialized institutions for colorectal disease in Japan. We analyzed the records of 147 patients who underwent prophylactic surgical treatment between 2000 and 2012. Patients were divided into Group 1 (2000–2006) and Group 2 (2007–2012) based on their date of surgery.

Results

Age at the time of prophylactic surgery was 27 and 31 years in Groups 1 and 2, respectively. The proportion of attenuated FAP was significantly lower in Group 2 than in Group 1 (1.0 vs. 13 %, respectively). Pathological examination revealed an increased incidence of malignant polyps in the resected specimens from Group 2 patients (10 vs. 23 %, respectively; P = 0.034). Laparoscopic surgery was more frequent in Group 2 than in Group 1 (61 vs. 40 %, respectively). There was no surgical mortality in either group.

Conclusion

Prophylactic surgery for FAP results in good short-term surgical outcomes in Japan. The current surgical approach is characterized by limited surgical indications for patients with attenuated FAP, delayed timing of colectomy, and the increasing standardization of laparoscopic surgery.

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Up-regulation of small nucleolar RNA 78 is correlated with aggressive phenotype and poor prognosis of hepatocellular carcinoma

Abstract

Small nucleolar RNAs (snoRNAs) as a novel molecular species may have significant and comprehensive influences on the development and progression of hepatocellular carcinoma (HCC). We recently characterized snoRNA transcriptome signatures in HCC tissues by small RNA sequencing and found that small nucleolar RNA 78 (SNORD78) was associated with HCC. However, little is known about the pathological role of SNORD78 in HCC patients. This study aimed to profile SNORD78 expression signature and then to explore the pathogenesis of SNORD78 in HCC. The real-time PCR results showed that SNORD78 was greatly upregulated in HCC tissues than adjacent noncancerous tissues (p = 0.004). Correlation analysis showed that high-level expression of SNORD78 was notably associated with tumor number (single vs. multiply, p = 0.02), stage (I∼II vs. III∼IV, p = 0.014), and distant metastasis (absent vs. present, p = 0.01) in HCC patients. Univatiate and multivariate analyses showed that SNORD78 was a significant prognostic predictor for overall survival and recurrence-free survival of HCC patients (hazard ratio = 1.375, 95 % CI = 1.125–1.680, p = 0.002; hazard ratio = 1.418, 95 % CI = 1.201–1.675, p < 0.001). Moreover, Kaplan-Meier analysis showed that high-level expression of SNORD78 was associated with short overall survival and recurrence-free survival of HCC patients (p = 0.023, 0.014). Functionally, knockdown of SNORD78 significantly inhibited cellular proliferation, migration, and invasion of SK-Hep-1 via inducing G0/G1 cell cycle arrest and apoptosis. In conclusion, SNORD78 may be associated with aggressive phenotype and poor prognosis of HCC.

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Issue Information - Ed Board

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Issue Information - TOC

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Issue Information - Ed Board

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Issue Information - TOC

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Erratum to: Remifentanil for labor analgesia: a comprehensive review

http://ift.tt/2eBqrc8

Rare case of type I hypersensitivity reaction to sodium hypochlorite solution in a healthcare setting

Sodium hypochlorite is a clear yellowish solution with a characteristic odour of chlorine and is commonly used as a disinfectant and a bleaching agent. It is used in various healthcare settings for its fast-acting and broad-spectrum antimicrobial activity. It is a known irritant and there are some reports that it can also cause allergic contact dermatitis of type IV hypersensitivity. We report a case of work-related type I hypersensitivity to sodium hypochlorite, presenting with recurrent urticarial rash and a positive prick test reaction to this chemical. He was subsequently excused from further exposure with no further recurrences of the urticarial rash. To the best of our knowledge, this is the first such reported case due to work in the healthcare setting.

http://ift.tt/2erhXE5

Two tunnels for one peritoneal dialysis catheter: a case for caution

Description

Catheter tunnel infection (CTI) is a known cause of adverse outcomes in peritoneal dialysis (PD)-related peritonitis. Extension of exit site infection is the most common reported reason for CTI. We report a case of PD-related peritonitis due to a delayed surgical complication.

A man aged 54 years with a history of end-stage renal disease due to polycystic kidney disease, on continuous cycling PD for the past 5 years, presented with fever, abdominal pain and cloudy PD effluent. His abdomen was diffusely tender. Except for extruded external cuff, the PD catheter exit site was unremarkable. Serous drainage was noted 1 inch from the exit site where the surgical trocar had been inserted for laparoscopic PD catheter placement. The patient reported increasing drainage for 4 weeks prior to presentation. Laboratory studies were consistent with PD-related peritonitis with PD fluid white cell count of 470/mm³ and 64% neutrophils. Broad-spectrum antibiotics were initiated. The...

http://ift.tt/2efqa39

Rare cause of massive haemoptysis in pulmonary tuberculosis: Rasmussen's aneurysm

Description

A woman aged 48 years presented to the accident and emergency department with three episodes of massive haemoptysis of ~500 mL. On examination, her vitals were stable. She had a history of pulmonary tuberculosis 2 years prior to this episode for which she had taken a complete course of antituberculous drugs for 9 months and was symptom-free and sputum culture-negative at the end of treatment. Her blood routines showed leucocytosis and raised inflammatory markers (ESR). Sputum and bronchoalveolar lavage specimens were smear positive for acid-fast bacilli, thus she was diagnosed to have a relapse with active tuberculosis.

Imaging evaluation included a chest radiograph which showed cavitatory lesions with air fluid levels in bilateral lung fields with surrounding air space shadowing (figure 1). A plain multidetector CT (MDCT) was performed, which revealed multiple discrete cavities randomly distributed throughout both lungs (figure 2) and the largest cavity was...

http://ift.tt/2erkqyh

Mediastinal osteosarcoma metastasis causing right heart failure due to pulmonary trunk compression

Description

We present the case of a woman aged 27 years with a background of operated femoral osteosarcoma 9 months ago. She was transferred to our hospital with worsening shortness of breath and signs of decompensated heart failure, haemodynamic instability and suspicion of pericardial effusion. Her transthoracic echocardiogram ruled out a pericardial collection but revealed severe tricuspid regurgitation and right ventricular dilation (figure 1A). A chest CT scan demonstrated an anterior mediastinal mass causing pulmonary trunk compression with subsequent right heart strain and bilateral congestive pleural effusions (figure 1B,C). Haemodynamic instability dictated urgent palliative surgical debulking that was performed under local anaesthesia and sedation via an anterior mediastinotomy approach, due to anaesthetic concerns (figure 2A). This resulted in decompression of the pulmonary trunk and improvement in the patient condition to allow further oncological treatment. The subsequent histopathological examination confirmed osteosarcoma metastasis. Following oncological medical...

http://ift.tt/2efrgvu

Rare case of T-cell lymphoma presenting as acute myelopathy

Acute myelopathy is a rare presentation of systemic T-cell lymphoma. We present the case of a man aged 68 years with a diffuse erythematous maculopapular rash, followed by lower extremity paresthesias and progressive lower extremity weakness. Spinal MRI showed longitudinally extensive T2 hyperintensity with diffuse contrast enhancement. An atypical clonal T-lymphocyte population was identified in cerebrospinal fluid, peripheral blood and bone marrow aspirate, indicating a malignant T-cell lymphoproliferative disorder. The patient was treated with intrathecal and systemic chemotherapy. Unfortunately, he was not responsive to chemotherapy.

http://ift.tt/2erg9uH

Total recovery of optic nerve sheath meningioma

We reported the case of a 43-year-old woman with a rapid progressive visual loss. The diagnosis of primary optic nerve sheath meningioma was made thanks to atypia evolution, clinical and radiological findings. The patient was treated with an intensity-modulated radiotherapy of 50.4 Gy in 28 fractions 2 months after the diagnosis. Visual acuity and visual field were completely recovered after 2 years of follow-up. No late side effects of irradiation were recorded.

http://ift.tt/2efrfYs

Fine-needle aspiration versus core needle biopsy: Reconsidering the evidence of superiority

The choice of which invasive procedure to perform for pathologic diagnosis should be a careful analysis of the relative risks and benefits based on data rather than personal taste. Cytopathologists should take an active role in obtaining FNA samples which are adequate for both diagnosis and ancillary testing. This approach optimizes diagnostic accuracy and minimizes morbidity.

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Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease

Abstract

Extracellular vesicles (EVs) play key roles in glioblastoma (GBM) biology and represent novel sources of biomarkers that are detectable in the peripheral circulation. Despite this notionally non-invasive approach to assess GBM tumours in situ, a comprehensive GBM EV protein signature has not been described. Here, EVs secreted by six GBM cell lines were isolated and analysed by quantitative high-resolution mass spectrometry. Overall, 844 proteins were identified in the GBM EV proteome, of which 145 proteins were common to EVs secreted by all cell lines examined; included in the curated EV compendium (Vesiclepedia_559; http://ift.tt/WAcpwx). Levels of 14 EV proteins significantly correlated with cell invasion (invadopodia production; r² > 0.5, p < 0.05), including several proteins that interact with molecules responsible for regulating invadopodia formation. Invadopodia, actin-rich membrane protrusions with proteolytic activity, are associated with more aggressive disease and are sites of EV release. Gene levels corresponding to invasion-related EV proteins showed that five genes (annexin A1, actin-related protein 3, integrin-β1, insulin-like growth factor 2 receptor and programmed cell death 6-interacting protein) were significantly higher in GBM tumours compared to normal brain in silico, with common functions relating to actin polymerisation and endosomal sorting. We also show that Cavitron Ultrasonic Surgical Aspirator (CUSA) washings are a novel source of brain tumour-derived EVs, demonstrated by particle tracking analysis, TEM and proteome profiling. Quantitative proteomics corroborated the high levels of proposed invasion-related proteins in EVs enriched from a GBM compared to low-grade astrocytoma tumour. Large-scale clinical follow-up of putative biomarkers, particularly the proposed survival marker annexin A1, is warranted.

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Fine-needle aspiration versus core needle biopsy: Reconsidering the evidence of superiority

The choice of which invasive procedure to perform for pathologic diagnosis should be a careful analysis of the relative risks and benefits based on data rather than personal taste. Cytopathologists should take an active role in obtaining FNA samples which are adequate for both diagnosis and ancillary testing. This approach optimizes diagnostic accuracy and minimizes morbidity.

http://ift.tt/2eOO6d7

An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi

BACKGROUND

Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions.

METHODS

A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis.

RESULTS

The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%.

CONCLUSIONS

These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2016. © 2016 Myriad Genetics, Inc. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

http://ift.tt/2eAZe9q

An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi

BACKGROUND

Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions.

METHODS

A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis.

RESULTS

The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%.

CONCLUSIONS

These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2016. © 2016 Myriad Genetics, Inc. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

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Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2

Abstract

Background

Accumulating researches have shown that epithelial-mesenchymal transition (EMT) contributes to tumor metastasis. Leptin, a key adipokine secreted from adipocytes, shapes the tumor microenvironment, potentiates the migration of breast cancer cells and angiogenesis, and is also involved in EMT. However, the potential mechanism remains unknown. This study aims to explore the effect of leptin on EMT in breast cancer cells and the underlying mechanism.

Methods

With the assessment of EMT-associated marker expression in MCF-7, SK-BR-3, and MDA-MB-468 cells, the effect of leptin on breast cancer cells was analyzed. Besides, an array of pathway inhibitors as well as RNA interference targeting pyruvate kinase M2 (PKM2) were used to clarify the underlying mechanism of leptin-mediated EMT in vitro and in vivo.

Results

The results demonstrated that leptin promoted breast cancer cells EMT, visibly activated the PI3K/AKT signaling pathway, and upregulated PKM2 expression. An antibody against the leptin receptor (anti-ObR) and the PI3K/AKT signaling pathway inhibitor LY294002 significantly abolished leptin-induced PKM2 expression and EMT-associated marker expression. SiRNA targeting PKM2 partially abolished leptin-induced migration, invasion, and EMT-associated marker expression. In vivo xenograft experiments indicated that RNA interference against PKM2 suppressed breast cancer growth and metastasis.

Conclusions

Our data suggest that leptin promotes EMT in breast cancer cells via the upregulation of PKM2 expression as well as activation of PI3K/AKT signaling pathway, and PKM2 might be one of the key points and potential targets for breast cancer therapy.

http://ift.tt/2epYDsE

Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2

Abstract

Background

Accumulating researches have shown that epithelial-mesenchymal transition (EMT) contributes to tumor metastasis. Leptin, a key adipokine secreted from adipocytes, shapes the tumor microenvironment, potentiates the migration of breast cancer cells and angiogenesis, and is also involved in EMT. However, the potential mechanism remains unknown. This study aims to explore the effect of leptin on EMT in breast cancer cells and the underlying mechanism.

Methods

With the assessment of EMT-associated marker expression in MCF-7, SK-BR-3, and MDA-MB-468 cells, the effect of leptin on breast cancer cells was analyzed. Besides, an array of pathway inhibitors as well as RNA interference targeting pyruvate kinase M2 (PKM2) were used to clarify the underlying mechanism of leptin-mediated EMT in vitro and in vivo.

Results

The results demonstrated that leptin promoted breast cancer cells EMT, visibly activated the PI3K/AKT signaling pathway, and upregulated PKM2 expression. An antibody against the leptin receptor (anti-ObR) and the PI3K/AKT signaling pathway inhibitor LY294002 significantly abolished leptin-induced PKM2 expression and EMT-associated marker expression. SiRNA targeting PKM2 partially abolished leptin-induced migration, invasion, and EMT-associated marker expression. In vivo xenograft experiments indicated that RNA interference against PKM2 suppressed breast cancer growth and metastasis.

Conclusions

Our data suggest that leptin promotes EMT in breast cancer cells via the upregulation of PKM2 expression as well as activation of PI3K/AKT signaling pathway, and PKM2 might be one of the key points and potential targets for breast cancer therapy.

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Mycophenolate mofetil is effective only for involved skin in the treatment for steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

http://ift.tt/2edg3cw

The possible role of burden of therapy on the risk of myeloma extramedullary spread

Abstract

Extramedullary relapse (EMR) represents a poor prognostic marker in the course of multiple myeloma (MM). We reviewed data from 329 patients, diagnosed between 2000 and 2010, without extramedullary disease at onset to explore possible risk factors for EMR. The median overall survival of our study cohort was 6.4 years. The risk of EMR was 28 % with a median time from diagnosis to first EMR of 2.2 years (0.2–9.1 years). Patients with soft tissue masses located in extra-osseous organs (EMR-S) showed the worst outcome, compared to those with tumor masses arising from adjacent bone (EMR-B) (median OS 1.6 vs 2.4 years, p = 0.006). In addition, patients with EMR-S showed a significant trend for further development of extramedullary masses in a very short time (3.7 vs 5.7 months for EMR-B, p = 0.043). Multivariate analysis failed to identify any clinically presenting features predictive for EMR. The occurrence of EMR was higher in patients with more complex treatment history, defined on the basis of longer treatment duration (≥6 vs <6 months) and on elevated number of treatment lines administered (>2 vs ≤2 lines) (HR = 4.5, p < 0.001 and HR = 9.0, p < 0.001, respectively, when one or both factors are present).In conclusion, increasing burden of treatment might be a possible risk factor for EMR. MM patients with multiple relapses should be comprehensively investigated including, when possible, a whole-body-targeted radiologic technique to accurately detect EMR. Treatment choice should take into account the very poor outcome for patients with soft tissue involvement.

http://ift.tt/2eAPmwz

HLA-haploidentical hematopoietic stem cell transplantation with low-dose thymoglobulin GVHD prophylaxis for an adult T cell leukemia/lymphoma patient treated with pretransplant mogamulizumab

http://ift.tt/2edeE5V

Intermittent versus continuous androgen deprivation therapy to biochemical recurrence after external beam radiotherapy: a phase 3 GICOR study

Abstract

Purpose

We compared biochemical control and quality of life with intermittent (6 months) versus continuous (36 months) androgen deprivation therapy (ADT) in a non-inferiority randomized phase 3 trial in patients with biochemical failure (BF) after external beam radical radiotherapy (EBRT).

Materials and methods

Patients were stratified according to the Gleason score (GS) and were classified as low risk with a GS < 6 and 7 (3 + 4) and high risk with a GS of 7 (4 + 3) and >7. Patients were followed with PSA determinations and quality-of-life assessments (QLQ C-30 and QLQ PR-25) every 6 months for a period of 3 years. BF after radiation was defined as a PSA level of nadir +2 ng/ml. Disease progression (DP) after ADT was defined as PSA ≥4 ng/ml (BF) and/or metastases.

Results

Seventy-seven patients were included in this multicenter phase 3 trial from 2005 to 2009. Thirty-eight and 39 patients were included in the intermittent and continuous groups, respectively. The median follow-up for both groups was 48 months (40–68). DP after ADT in the intermittent group was seen in three patients (distant metastases in one patient) versus 0 in the continuous group. The QLQ-C30 and QLQ PR-25 scores did not show any statistically difference between the two ADT groups.

Conclusions

No significant differences were seen in DP and QLQ between intermittent (6 months) and continuous (36 months) ADT in patients with BF after EBRT.

http://ift.tt/2dUlfiF

Intermittent versus continuous androgen deprivation therapy to biochemical recurrence after external beam radiotherapy: a phase 3 GICOR study

Abstract

Purpose

We compared biochemical control and quality of life with intermittent (6 months) versus continuous (36 months) androgen deprivation therapy (ADT) in a non-inferiority randomized phase 3 trial in patients with biochemical failure (BF) after external beam radical radiotherapy (EBRT).

Materials and methods

Patients were stratified according to the Gleason score (GS) and were classified as low risk with a GS < 6 and 7 (3 + 4) and high risk with a GS of 7 (4 + 3) and >7. Patients were followed with PSA determinations and quality-of-life assessments (QLQ C-30 and QLQ PR-25) every 6 months for a period of 3 years. BF after radiation was defined as a PSA level of nadir +2 ng/ml. Disease progression (DP) after ADT was defined as PSA ≥4 ng/ml (BF) and/or metastases.

Results

Seventy-seven patients were included in this multicenter phase 3 trial from 2005 to 2009. Thirty-eight and 39 patients were included in the intermittent and continuous groups, respectively. The median follow-up for both groups was 48 months (40–68). DP after ADT in the intermittent group was seen in three patients (distant metastases in one patient) versus 0 in the continuous group. The QLQ-C30 and QLQ PR-25 scores did not show any statistically difference between the two ADT groups.

Conclusions

No significant differences were seen in DP and QLQ between intermittent (6 months) and continuous (36 months) ADT in patients with BF after EBRT.

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A treatment planning study of proton arc therapy for para-aortic lymph node tumors: dosimetric evaluation of conventional proton therapy, proton arc therapy, and intensity modulated radiotherapy

Abstract

Background

The purpose of this study is to evaluate the dosimetric benefits of a proton arc technique for treating tumors of the para-aortic lymph nodes (PALN).

Method

In nine patients, a proton arc therapy (PAT) technique was compared with intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) techniques with respect to the planning target volume (PTV) and organs at risk (OAR). PTV coverage, conformity index (CI), homogeneity index (HI) and OAR doses were compared. Organ-specific radiation induced cancer risks were estimated by applying organ equivalent dose (OED) and normal tissue complication probability (NTCP).

Results

The PAT techniques showed better PTV coverage than IMRT and PBT plans. The CI obtained with PAT was 1.19 ± 0.02, which was significantly better than that for the IMRT techniques. The HI was lowest for the PAT plan and highest for IMRT. The dose to the OARs was always below the acceptable limits and comparable for all three techniques. OED results calculated based on a plateau dose–response model showed that the risk of secondary cancers in organs was much higher when IMRT or PBT were employed than when PAT was used. NTCPs of PAT to the stomach (0.29 %), small bowel (0.69 %) and liver (0.38 %) were substantially lower than those of IMRT and PBT.

Conclusion

This study demonstrates that there is a potential role for PAT as a commercialized instrument in the future to proton therapy.

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Suspected recurrence of brain metastases after focused high dose radiotherapy: can [ 18 F]FET- PET overcome diagnostic uncertainties?

Abstract

Background

After focused high dose radiotherapy of brain metastases, differentiation between tumor recurrence and radiation-induced lesions by conventional MRI is challenging. This study investigates the usefulness of dynamic O-(2-¹⁸F-Fluoroethyl)-L-Tyrosine positron emission tomography (¹⁸F-FET PET) in patients with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy of brain metastases.

Methods

Twenty-two patients with 34 brain metastases (median age 61.9 years) were included. Due to follow-up scan evaluations after repeated treatment in a subset of patients, a total of 50 lesions with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy could be evaluated. ¹⁸F-FET PET analysis included the assessment of maximum and mean tumor-to-background ratio (TBR_max and TBR_mean) and analysis of time-activity-curves (TAC; increasing vs. decreasing) including minimal time-to-peak (TTP_min). PET parameters were correlated with histological findings and radiological-clinical follow-up evaluation.

Results

Tumor recurrence was found in 21/50 cases (15/21 verified by histology, 6/21 by radiological-clinical follow-up) and radiation-induced changes in 29/50 cases (5/29 verified by histology, 24/29 by radiological-clinical follow-up). Median clinical-radiological follow-up was 28.3 months (range 4.2–99.1 months). ¹⁸F-FET uptake was higher in tumor recurrence compared to radiation-induced changes (TBR_max 2.9 vs. 2.0, p < 0.001; TBR_mean 2.2 vs. 1.7, p < 0.001). Receiver-operating-characteristic (ROC) curve analysis revealed optimal cut-off values of 2.15 for TBR_max and 1.95 for TBR_mean (sensitivity 86 %, specificity 79 %). Increasing TACs and long TTP_min were associated with radiation-induced changes, decreasing TACs with tumor recurrence (p = 0.01). By combination of TBR and TACs, sensitivity and specificity could be increased to 93 and 84 %.

Conclusions

In patients with MRI-suspected tumor recurrence after focused high dose radiotherapy, ¹⁸F-FET PET has a high sensitivity and specificity for the differentiation of vital tumor tissue and radiation-induced lesions.

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A treatment planning study of proton arc therapy for para-aortic lymph node tumors: dosimetric evaluation of conventional proton therapy, proton arc therapy, and intensity modulated radiotherapy

Abstract

Background

The purpose of this study is to evaluate the dosimetric benefits of a proton arc technique for treating tumors of the para-aortic lymph nodes (PALN).

Method

In nine patients, a proton arc therapy (PAT) technique was compared with intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) techniques with respect to the planning target volume (PTV) and organs at risk (OAR). PTV coverage, conformity index (CI), homogeneity index (HI) and OAR doses were compared. Organ-specific radiation induced cancer risks were estimated by applying organ equivalent dose (OED) and normal tissue complication probability (NTCP).

Results

The PAT techniques showed better PTV coverage than IMRT and PBT plans. The CI obtained with PAT was 1.19 ± 0.02, which was significantly better than that for the IMRT techniques. The HI was lowest for the PAT plan and highest for IMRT. The dose to the OARs was always below the acceptable limits and comparable for all three techniques. OED results calculated based on a plateau dose–response model showed that the risk of secondary cancers in organs was much higher when IMRT or PBT were employed than when PAT was used. NTCPs of PAT to the stomach (0.29 %), small bowel (0.69 %) and liver (0.38 %) were substantially lower than those of IMRT and PBT.

Conclusion

This study demonstrates that there is a potential role for PAT as a commercialized instrument in the future to proton therapy.

http://ift.tt/2dFYxwT

Suspected recurrence of brain metastases after focused high dose radiotherapy: can [ 18 F]FET- PET overcome diagnostic uncertainties?

Abstract

Background

After focused high dose radiotherapy of brain metastases, differentiation between tumor recurrence and radiation-induced lesions by conventional MRI is challenging. This study investigates the usefulness of dynamic O-(2-¹⁸F-Fluoroethyl)-L-Tyrosine positron emission tomography (¹⁸F-FET PET) in patients with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy of brain metastases.

Methods

Twenty-two patients with 34 brain metastases (median age 61.9 years) were included. Due to follow-up scan evaluations after repeated treatment in a subset of patients, a total of 50 lesions with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy could be evaluated. ¹⁸F-FET PET analysis included the assessment of maximum and mean tumor-to-background ratio (TBR_max and TBR_mean) and analysis of time-activity-curves (TAC; increasing vs. decreasing) including minimal time-to-peak (TTP_min). PET parameters were correlated with histological findings and radiological-clinical follow-up evaluation.

Results

Tumor recurrence was found in 21/50 cases (15/21 verified by histology, 6/21 by radiological-clinical follow-up) and radiation-induced changes in 29/50 cases (5/29 verified by histology, 24/29 by radiological-clinical follow-up). Median clinical-radiological follow-up was 28.3 months (range 4.2–99.1 months). ¹⁸F-FET uptake was higher in tumor recurrence compared to radiation-induced changes (TBR_max 2.9 vs. 2.0, p < 0.001; TBR_mean 2.2 vs. 1.7, p < 0.001). Receiver-operating-characteristic (ROC) curve analysis revealed optimal cut-off values of 2.15 for TBR_max and 1.95 for TBR_mean (sensitivity 86 %, specificity 79 %). Increasing TACs and long TTP_min were associated with radiation-induced changes, decreasing TACs with tumor recurrence (p = 0.01). By combination of TBR and TACs, sensitivity and specificity could be increased to 93 and 84 %.

Conclusions

In patients with MRI-suspected tumor recurrence after focused high dose radiotherapy, ¹⁸F-FET PET has a high sensitivity and specificity for the differentiation of vital tumor tissue and radiation-induced lesions.

http://ift.tt/2eAaXEk

Cataract Surgery with a New Fluidics Control Phacoemulsification System in Nanophthalmic Eyes

Purpose: To report visual outcomes and complications after cataract surgery in nanophthalmic eyes with a phacoemulsification system using the active fluidics control strategy. Methods: This is a retrospective case series. All eyes with an axial length of less than 20 mm that underwent cataract surgery or refractive lens exchange using the Centurion Vision System (Alcon Laboratories Inc.) in Hong Kong Sanatorium and Hospital were evaluated. The visual acuity and intraoperative and postoperative complications were reported. Prior approval from the Hospital Research Committee has been granted. Results: Five eyes of 3 patients were included. The mean follow-up period was 10.2 ± 5.3 months (range, 4–18). Two eyes (40%) had a one-line loss of corrected distance visual acuity. No uveal effusion and posterior capsular tear developed. An optic crack and haptic breakage in the intraocular lens developed in 1 eye (20%) and 2 eyes (40%), respectively. Additional surgeries to treat high postoperative intraocular pressure were required in 1 eye (20%). Conclusion: The use of a new phacoemulsification system, which actively monitors and maintains the intraoperative pressure, facilitated anterior chamber stability during cataract surgery in nanophthalmic eyes. This minimized the risk of major complications related to unstable anterior chambers such as uveal effusion and posterior capsular tear. Development of intraoperative crack/breakage in a high-power intraocular lens was common.
Case Rep Ophthalmol 2016;7:218–226

http://ift.tt/2eeAOa5

Cancers, Vol. 8, Pages 97: The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

The TAM receptor protein tyrosine kinases—Tyro3, Axl, and Mer—are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy.

http://ift.tt/2dFzVUS

Cancers, Vol. 8, Pages 97: The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

The TAM receptor protein tyrosine kinases—Tyro3, Axl, and Mer—are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy.

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Duration of response to first androgen deprivation therapy, time to castration resistance prostate cancer, and outcome of metastatic castration resistance prostate cancer patients treated with abiraterone acetate.

Abiraterone acetate (AA) demonstrated its efficacy in the treatment of patients with metastatic castration resistance prostate cancer (mCRPC) in predocetaxel and postdocetaxel setting. However, we learn from pivotal studies that forms of primary and acquired resistance to this drug exist. Patient selection becomes so crucial to optimize treatment results. Potential predictive biomarkers have been identified but are not yet validated. In this scenario, clinical features and disease characteristics may still be of value in selecting patients for different treatments. The objective of this retrospective study was to assess whether or not a correlation between duration of response to first androgen deprivation therapy (ADT), time to castration-resistant prostate cancer (TTCRPC), and outcome of AA therapy exists. A retrospective analysis of clinical data of mCRPC patients treated with AA at two Italian cancer centers was carried out. The Kaplan-Meier method and Cox proportional hazard model were used to analyze survival data. Correlation between median duration of response to first ADT or median TTCRPC and the outcome of patients treated with AA was analyzed. From January 2015 to November 2015, data of 59 patients with mCRPC were collected. We observed no differences in patient's median progression-free survival (PFS) and biochemical progression-free survival (bPFS), according to both median duration of response to first-line ADT (duration of first ADT=13 months: median PFS and bPFS were 9 and 6 months, respectively) and median TTCRPC (TTCRPC=28 months: median PFS and bPFS were 10 and 9 months, respectively). Overall survival, in the same group, did not differ between patients with a duration of response to first ADT over or under 13 months (P=0.90) but in patients with a TTCRPC of 28 months or more, there was a trend toward longer survival than patients with TTCRPC less than 28 months (5-year overall survival was 74 vs. 50%; P=0.14). The duration of response to first-line ADT and the TTCRPC showed no significant association with outcome of AA therapy in patients with mCRPC. However, large prospective trials are desirable to confirm these data. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2emALHm

Duration of response to first androgen deprivation therapy, time to castration resistance prostate cancer, and outcome of metastatic castration resistance prostate cancer patients treated with abiraterone acetate.

Abiraterone acetate (AA) demonstrated its efficacy in the treatment of patients with metastatic castration resistance prostate cancer (mCRPC) in predocetaxel and postdocetaxel setting. However, we learn from pivotal studies that forms of primary and acquired resistance to this drug exist. Patient selection becomes so crucial to optimize treatment results. Potential predictive biomarkers have been identified but are not yet validated. In this scenario, clinical features and disease characteristics may still be of value in selecting patients for different treatments. The objective of this retrospective study was to assess whether or not a correlation between duration of response to first androgen deprivation therapy (ADT), time to castration-resistant prostate cancer (TTCRPC), and outcome of AA therapy exists. A retrospective analysis of clinical data of mCRPC patients treated with AA at two Italian cancer centers was carried out. The Kaplan-Meier method and Cox proportional hazard model were used to analyze survival data. Correlation between median duration of response to first ADT or median TTCRPC and the outcome of patients treated with AA was analyzed. From January 2015 to November 2015, data of 59 patients with mCRPC were collected. We observed no differences in patient's median progression-free survival (PFS) and biochemical progression-free survival (bPFS), according to both median duration of response to first-line ADT (duration of first ADT=13 months: median PFS and bPFS were 9 and 6 months, respectively) and median TTCRPC (TTCRPC=28 months: median PFS and bPFS were 10 and 9 months, respectively). Overall survival, in the same group, did not differ between patients with a duration of response to first ADT over or under 13 months (P=0.90) but in patients with a TTCRPC of 28 months or more, there was a trend toward longer survival than patients with TTCRPC less than 28 months (5-year overall survival was 74 vs. 50%; P=0.14). The duration of response to first-line ADT and the TTCRPC showed no significant association with outcome of AA therapy in patients with mCRPC. However, large prospective trials are desirable to confirm these data. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma

http://ift.tt/2eNRwwH

Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2

Accumulating researches have shown that epithelial-mesenchymal transition (EMT) contributes to tumor metastasis. Leptin, a key adipokine secreted from adipocytes, shapes the tumor microenvironment, potentiates...

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